500 shareholders will force Facebook to file more paperwork with the SEC, it won't force Facebook onto the NYSE or NASDAQ. When that point is reached, it may be in Facebook's best interest to have an IPO, but they will not be required by law to do so. Update: CNN article discusses likely Facebook IPO in 2012. When companies have more than 500 shareholders, they're required to make significant financial disclosures -- though they can choose to remain private and keep their stock from trading publicly. However, most companies facing mandatory disclosures opt to go public. The Securities and Exchange Commission gives businesses lots of time to prepare for that milestone. Companies have until 120 days after the end of the fiscal year in which they cross the 500-shareholder line to begin making their disclosures. If Facebook tips the scale this year, that gives it until April 2012 to start filing financial reports.\"","title":""}],"string":"[\n {\n \"docid\": \"305544\",\n \"text\": \"\\\"The SEC requires a certain format when submitting filings, which generally does not line up with how documents are typeset for printing. Rather than typeset the entire document again, it's just sort of accepted that the format in EDGAR will suck. Typesetters actually call the process \\\"\\\"EDGARizing.\\\"\\\" (I'm not making this up, I used to work in the department at a mutual fund company that put together the financial reports for the funds.) My guess is it's a relic from legacy systems at the SEC that can't handle newer formats like PDF.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"391291\",\n \"text\": \"Yes it is true. The US based companies have to meet the requirements placed on them by the US government. The agency with all these reports is the Security and Exchange Commission. They run the EDGAR system to hold all those required reports The SEC’s EDGAR database provides free public access to corporate information, allowing you to quickly research a company’s financial information and operations by reviewing registration statements, prospectuses and periodic reports filed on Forms 10-K and 10-Q. You also can find information about recent corporate events reported on Form 8-K but that a company does not have to disclose to investors. EDGAR also provides access to comment and response letters relating to disclosure filings made after August 1, 2004, and reviewed by either the Division of Corporation Finance or the Division of Investment Management. On May 22, 2006, the staffs of the Divisions of Corporation Finance and Investment Management began to use the EDGAR system to issue notifications of effectiveness for Securities Act registration statements and post-effective amendments, other than those that become effective automatically by law. These notifications will be posted to the EDGAR system the morning after a filing is determined to be effective. As pointed out by Grade 'Eh' Bacon: Other countries may require different types of information to be reported to the public, in particular, financial statements. To find the financial statements released for a particular company, you can go to the appropriate stock exchange, or often simply the company's corporate website.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"399284\",\n \"text\": \"Compensation information is available in the annual reports (10-k filings) which are available from the SEC EDGAR system or, generally, the company's website. Additionally, insider transactions are reported to the SEC so you can see when an insider buys or sells stock or exercises options received as compensation. Background: Nowadays board and officers seem to secretly steal money from shareholders through options and other ways. The stock buybacks that people think should boost the earnings per stock is in reality issued back to the management of the company and is a more stealth way to take money from the company compared to take higher salaries. ... How do you know this is happening if you don't know where to go to get the data needed to determine whether or not this is happening? Do you really think company share buybacks involve just the amount of shares to pay an executive? Apple has bought back $117,000,000,000 worth of shares from the fourth quarter 2012 through the second quarter 2016, and paid a pretty substantial amount in dividends over the same period. Do you really think these shares were simply handed to the executives? The huge pension funds and other huge investors would not let this slide for very long if it were even close to being true. Don't come to an unfounded conclusion then seek data to prove your position. Look at and analyze data THEN come to a conclusion.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"56292\",\n \"text\": \"\\\"Edgar Online has this information for companies under SEC regulations and they are reported in \\\"\\\"Form 4\\\"\\\" so that should help guide your search\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"92593\",\n \"text\": \"Edgar Online is the SEC's reporting repository where public companies post their forms, these forms contain financial data Stock screeners allow you to compare many companies based on many financial metrics. Many sites have them, Google Finance has one with a decent amount of utility\",\n \"title\": \"\"\n },\n {\n \"docid\": \"125981\",\n \"text\": \"You can find out the general types of investments by reading the public corporation 10-Q report that is filed with the SEC it can be accessed via the EDGAR system. It will not tell you what securities they have, but it does identify the short term and long term investments categories and their value.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"441155\",\n \"text\": \"Schedule 13D (or the abbreviated version, schedule 13G) would be the most likely place to find this info. When a person or group of persons acquires beneficial ownership of more than 5% of a voting class of a company’s equity securities registered under Section 12 of the Securities Exchange Act of 1934, they are required to file a Schedule 13D with the SEC. Schedule 13D reports the acquisition and other information within ten days after the purchase. Any material changes in the facts contained in the schedule require a prompt amendment. You can find the Schedules 13D for most publicly traded companies in the SEC’s EDGAR database. A 1% change in the amount of ownership is considered material.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"502560\",\n \"text\": \"\\\"Crowdfunding can be a legitimate means of funding very small startups. It is an innovative, but obviously risky, method of raising small amounts of money. As such it is now regulated by the SEC under \\\"\\\"Regulation Crowdfunding\\\"\\\" They have published guides for these types of business startups to help them with required disclosures and reporting requirements: https://www.sec.gov/info/smallbus/secg/rccomplianceguide-051316.htm Here's the introduction to the relevant regulatory authority of the SEC: Under the Securities Act of 1933, the offer and sale of securities must be registered unless an exemption from registration is available. Title III of the Jumpstart Our Business Startups (JOBS) Act of 2012 added Securities Act Section 4(a)(6) that provides an exemption from registration for certain crowdfunding transactions.[2] In 2015, the Commission adopted Regulation Crowdfunding to implement the requirements of Title III.[3] Under the rules, eligible companies will be allowed to raise capital using Regulation Crowdfunding starting May 16, 2016. It is obviously a new form of investment but you should be able to get historical data on the SEC's real time Edgar reporting system once there is some history. This is a search for all Form C's filed as of 12/2/16\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"347523\",\n \"text\": \"according to the SEC: Shareholder Reports A mutual fund and a closed-end fund respectively must provide shareholders with annual and semi-annual reports 60 days after the end of the fund’s fiscal year and 60 days after the fund’s fiscal mid-year. These reports contain updated financial information, a list of the fund’s portfolio securities, and other information. The information in the shareholder reports will be current as of the date of the particular report (that is, the last day of the fund’s fiscal year for the annual report, and the last day of the fund’s fiscal mid-year for the semi-annual report). Other Reports A mutual fund and a closed-end fund must file a Form N-Q each quarter and a Form N-PX each year on the SEC’s EDGAR database, although funds are not required to mail these reports to shareholders. Funds disclose portfolio holdings on Form N-Q. Form N-PX identifies specific proposals on which the fund has voted portfolio securities over the past year and discloses how the fund voted on each. This disclosure enables fund shareholders to monitor their funds’ involvement in the governance activities of portfolio companies. which means that sixty days after the end of each quarter they will tell you what they owned 60 days ago. This makes sense; why would they want to tell the world what companies they are buying and selling.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"545558\",\n \"text\": \"There could be an impact on Facebook because just before the IPO, Morgan Stanley apparently sent information to selected clients that their analysts had just lowered their valuation of the company. There were also reports yesterday that the lowered valuation came about because Facebook sent some revised preliminary estimates of second quarter earnings (showing lower than expected earnings) to Morgan Stanley, and least one talking head said that Facebook might also face charges depending on what the cover letters and the e-mails back and forth between Facebook and Morgan Stanley said. Investigations have already been opened. Yes, a company wants to sell the stock being offered at the IPO at the highest price possible, but if it misled the public when offering the stock for sale (through its underwriters), it can also be liable, possibly even criminally liable. Material added in Edit: In fact, a lawsuit has already been filed in the US District Court in Manhattan in this matter. Whether the SEC ever does anything about the matter remains to be seen.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"63848\",\n \"text\": \"The only way for a mutual fund to default is if it inflated the NAV. I.e.: it reports that its investments worth more than they really are. Then, in case of a run on the fund, it may end up defaulting since it won't have the money to redeem shares at the NAV it published. When does it happen? When the fund is mismanaged or is a scam. This happened, for example, to the fund Madoff was managing. This is generally a sign of a Ponzi scheme or embezzlement. How can you ensure the funds you invest in are not affected by this? You'll have to read the fund reports, check the independent auditors' reports and check for clues. Generally, this is the job of the SEC - that's what they do as regulators. But for smaller funds, and private (i.e.: not public) investment companies, SEC may not be posing too much regulations.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"31516\",\n \"text\": \"You can take a look at EDGAR (Electronic Data Gathering, Analysis, and Retrieval), a big database run by the SEC where all companies, foreign and domestic, are required to file registration statements, periodic reports, and other forms electronically.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"553066\",\n \"text\": \"SEC forms are required when declaring insider activity. An insider is defined by the SEC to be a person or entity which (i) beneficially owns 10% or more of the outstanding shares of the company, (ii) is an officer or director of the company, or (iii), in the case of insider trading, does so based on knowledge which is not otherwise publically available at the time. At any rate, the person or entity trading the stock is required to file certain forms. Form 3 is filed when a person first transitions into the status of an insider (by becoming an officer, director, or beneficial owner of a certain percentage of stock). Form 4 is filed when an existing insider trades stock under the company's symbol. Form 5 is filed when certain insider trades of small value are reported later than usual. *More information can be found at the SEC's website. Another possibility is that a large number of options or derivatives were exercised by an officer, director, or lending institution. In the cases of officers or directors, this would need to be declared with an SEC form 4. For an institution exercising warrants obtained as a result of a lending agreement, either form 3 or 4 would need to be filed. In addition to the above possibilities, username passing through pointed out a very likely scenario in his answer, as well.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"27067\",\n \"text\": \"My company has a dashboard that basically does this. We select industries / companies we want to be notified of and we get an email in outlook when a new analyst note, research report, or SEC filing is posted on that industry or company.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"161411\",\n \"text\": \"\\\"For US equities, Edgar Online is where companies post their government filings to the SEC. On Google Finance, you would look at the \\\"\\\"SEC filings\\\"\\\" link on the page, and then find their 10K and 10Q documents, where that information is listed and already calculated. Many companies also have these same documents posted on their Investor Relations web pages.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"11263\",\n \"text\": \"The actual financial statements should always be referenced first before opening or closing a position. For US companies, they are freely available on EDGAR. Annual reports are called 10-Ks, and quarterly reports are called 10-Qs. YHOO and GOOG do a great job of posting financials that are quickly available, but money.msn has the best. These should be starting point, quick references. As you can see, they may all have the same strange accounting. Sometimes, it's difficult to find the information one seeks in the consolidated financial statements as in this case, so searching through the filing is necessary. The notes can be helpful, but Ctrl-F seems to do everything I need when I want something in a report. In AAPL's case, the Interest expense can be found in Note 3.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"327814\",\n \"text\": \"First utilize a security screener to identify the security profiles you are looking to identify for identifying your target securities for shorting. Most online brokers have stock screeners that you can utilize. At this point you may want to look at your target list of securities to find out those that are eligible for shorting. The SHO thresold list is also a good place to look for securities that are hard to borrow to eliminate potential target securities. http://regsho.finra.org/regsho-Index.html Also your broker can let you know the stocks that are available for borrowing. You can then take your target securities and then you can look at the corporate filings on the SEC's Edgar site to look for the key words you are looking for. I would suggest that you utilize XBRL so you can electronically run your key word searched in an automated manner. I would further suggest that you can run the key word XBRL daily for issuer filings of your target list of securities. Additional word searches you may want to consider are those that could indicate a dilution of the companies stock such as the issuance of convertible debt. Also the below link detailing real short interest may be helpful. Clearing firms are required to report short interest every two weeks. http://www.nasdaq.com/quotes/short-interest.aspx\",\n \"title\": \"\"\n },\n {\n \"docid\": \"251303\",\n \"text\": \"You can avoid companies that might go bankrupt by not buying the stock of companies with debt. Every quarter, a public company must file financials with the EDGAR system called a 10-Q. This filing includes unaudited financial statements and provides a continuing view of the company's financial position during the year. Any debt the company has acquired will appear on this filing and their annual report. If servicing the debt is costing the company a substantial fraction of their income, then the company is a bankruptcy risk.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"174714\",\n \"text\": \"\\\"When you pay the flight, hotel, conference attendance fees of $100: When you repay the credit card debt of $100: When you receive the gross salary of $5000: Your final balance sheet will show: Your final income statement will show: Under this method, your \\\"\\\"Salary\\\"\\\" account will show the salary net of business expense. The drawback is that the $4900 does not agree with your official documentation. For tax reporting purposes, you report $5000 to the tax agency, and if possible, report the $100 as Unreimbursed Employee Expenses (you weren't officially reimbursed). For more details see IRS Publication 529.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"146076\",\n \"text\": \"\\\"Publicly traded companies files 10-Ks with the SEC, searchable on the EDGAR system. If you want basic financial statement info then look for 10-Ks that are marked \\\"\\\"Interactive Data\\\"\\\", as for those the SEC has broken everything out by statement into standard formats. You could also use marketwatch which puts everything in financial statements into the same or as similar of categories as it can to make it easier to compare companies.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"191677\",\n \"text\": \"10-Q is the quarterly report, and accordingly is filed quarterly. Similarly, 10-K is the annual report. 8-K is a general form for notification of material events. It is filed every time a material event is required to be reported to the shareholders. It may accompany the periodical reports, but doesn't have to. It can be filed on its own. If you're only interested in the financial statements, then you should be looking for the 10K/10Q forms. SEC will tell you when the forms were filed (dates), but it won't tell you what's more material and what's less. So you can plot a stock price graph on these dates, and see what was deemed more material by the investors based on the price fluctuations, but be prepared to find fluctuations that have no correlation to filings - because the market as a whole can drag the stock up or down. Also, some events may not be required to be reported to SEC, but may be deemed material by the investors. For example, a Cupertino town hall meeting discussing the zoning for the new AAPL HQ building may be deemed material by the investors, based on the sentiments, even if no decision was made to be reported to SEC.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"246586\",\n \"text\": \"Brokerage firms are required to report the number of shares being shorted. This information is reported to the exchange (NYSE of NASDAQ) and is made public. Most financial sites indicate the number of shares being shorted for a particular stock. The image below from Yahoo finance shows 3.29 million shares of CMG were being shorted at the close of 9-28-2012. This is over 12% of the total outstanding shares of CMG. For naked short selling additional information is tracked. If the brokerage is unable to borrow shares to deliver before the settlement date of a short sale then the transaction is recorded as fails-to-deliver. No money or shares are exchanged since the brokerage is unable to deliver the shares that were agreed upon. A large amount of fails-to-deliver transactions for a stock usually indicates an excessive amount of naked shorting. When investors and brokerage firms start to aggressively short a stock they will do so without having borrowed the shares to sell. This will result in a large amount of naked short selling. When there are a large number of naked short sellers not all the sellers will be able to borrow the necessary shares before the settlement date and many fails-to-deliver transactions will be recorded. The SEC records the number of fails-to-deliver transactions. The table below summarizes the fails-to-deliver transactions from 1-1-2012 through 9-14-2012 (data obtained from here). The “Ext Amount” column shows the total dollar value of the transactions that failed ( i.e. Fail Qty * Share price ). The “Volume” column is the total number of shares traded in the same time period. The “% Volume” shows the percentage of shares that failed to deliver as a percentage of the total market volume. The table orders the data in descending order by the quantity of shares that were not delivered. Most of the companies at the top of the list no longer exist. For many of these companies, the quantity of shares that failed to deliver where many multiples of the number of shares traded during the same time period. This indicates massive naked short selling as many brokerages where unable to find shares to borrow before the settlement date. More information here.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"45718\",\n \"text\": \"\\\"I use online banking as much as possible and I think it may help you get closer to your goal. I see you want to know where the money goes and save time so it should work for you like it did for me. I used to charge everything or write checks and then pay a big visa bill. My problem was I never knew exactly how much I spent because neither Visa or check writing are record systems. They just generate transactions records. I made it a goal use online banking to match my spending to the available cash and ended up ok usually 9-10 months out of the year. I started with direct deposit of my paycheck. Each Saturday, I sit down and within a half hour, I've paid the bills for the week and know where I stand for the following week. Any new bill that comes in, I add it to online banking even if it's not a recurring expense. I also pull down cash from the ATM but just enough to allow me to do what I have to do. If it's more than $30 or $40 bucks, I use the debit card so that expense goes right to the online bank statement. My monthly bank statement gives me a single report with everything listed. Mortgage, utilities, car payment, cable bill, phone bill, insurance, newspaper, etc... It does not record these transactions in generic categories; they actually say Verizon or Comcast or Shop Rite. I found this serves as the only report I need to see what's happening with my budget. It may take a while to change to a plan like this one. but you'll now have a system that shows you in a single place where the money goes. Move all bills that are \\\"\\\"auto-pay\\\"\\\" to the online system and watch your Visa bill go down. The invested time is likely what you're doing now writing checks. Hope this helps.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"457667\",\n \"text\": \"I've been budgeting with MS Money since 2004 and was pretty disappointed to hear it's being discontinued. Budgeting is actually a stress-relieving hobby for me, and I can be a bit of a control-freak when it comes to finances, so I decided to start early looking for a replacement rather than waiting until MS Money can no longer download transactions. Here are the pros and cons of the ones I've tried (updated 10/2010): You Need A Budget Pro (YNAB) - Based on the old envelopes system, YNAB has you allot money from each paycheck to a specific budget category (envelope). It encourages you to live on last money's income, and if you have trouble with overspending, that can be a great plan. Personally, I'm a big believer in the envelope concept, so that's the biggest pro I found. Also, it's a downloaded software, so once I've bought it (for about $50) it's mine, without forced upgrades as far as I've seen. The big con for me was that it does not automatically download transactions. I would have to sign on to each institution's website and manually download to the program. Also, coming from Money, I'm used to having features that YNAB doesn't offer, like the ability to store information about my accounts. Overall, it's forward-thinking and a good budgeting system, but will take some extra time to download transactions and isn't really a comprehensive management tool for all my financial needs. You can try it out with their free trial. Mint - This is a free online program. The free part was a major pro. It also looks pretty, if that's important to you. Updating is automatic, once you've got it all set up, so that's a pro. Mint's budgeting tools are so-so. Basically, you choose a category and tell it your limit. It yells at you (by text or email) when you cross the line, but doesn't seem to offer any other incentive to stay on budget. When I first looked at Mint, it did not connect with my credit union, but it currently connects to all my banks and all but one of my student loan institutions. Another recent improvement is that Mint now allows you to manually add transactions, including pending checks and cash transactions. The cons for me are that it does not give me a good end-of-the-month report, doesn't allow me to enter details of my paychecks, and doesn't give me any cash-flow forecasting. Overall, Mint is a good casual, retrospective, free online tool, but doesn't allow for much planning ahead. Mvelopes - Here's another online option, but this one is subscription-based. Again, we find the old envelopes system, which I think is smart, so that's a pro for me. It's online, so it downloads transactions automatically, but also allows you to manually add transactions, so another pro. The big con on this one is the cost. Depending on how you far ahead you choose to pay (quarterly, yearly or biannually), you're paying $7.60 to $12 per month. They do offer a free trial for 14 days (plus another 14 days offered when you try to cancel). Another con is that they don't provide meaningful reports. Overall, a good concept, but not worth the cost for me. Quicken - I hadn't tried Quicken earlier because they don't offer a free trial, but after the last few fell short, I landed with Quicken 2009. Pro for Quicken, as an MS Money user is that it is remarkably similar in format and options. The registers and reports are nearly identical. One frustration I'd had with Money was that it was ridiculously slow at start-up, and after a year or so of entering data, Quicken is dragging. Con for Quicken, again as an MS Money user, is that it's budgeting is not as detailed as I would like. Also, it does not download transactions smoothly now that my banks all ask security questions as part of sign-in. I have to sign in to my bank's website and manually download. Quicken 2011 is out now, but I haven't tried it yet. Hopefully they've solved the problem of security questions. Quicken 2011 promises an improved cash-flow forecast, which sounds promising, and was a feature of MS Money that I have very much missed. Haven't decided yet if it's worth the $50 to upgrade to 2011.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"548596\",\n \"text\": \"For months prior to going public a company has to file financial documents with the SEC. These are available to the public at www.sec.gov on their Edgar database. For instance, Eagleline is listed as potentially IPOing next week. You can find out all the details of any IPO including correspondence between the company and the SEC on Edgar. Here's the link for Eagleline (disclaimer, I have not investigated this company. It is an example only) https://www.sec.gov/cgi-bin/browse-edgar?action=getcompany&CIK=0001675776&owner=exclude&count=40 The most important, complex, and thorough document is the initial registration statement, usually an S-1, and subsequent amendments that occur as a result of new information or SEC questions. You can often get insight into a new public company by looking at the changes that have occurred in amendments since their initial filings. I highly advise people starting out to first look at the filings of companies they work for or know the industry intimately. This will help you to better understand the filings from companies you may not be so familiar with. A word of caution. Markets and company filings are followed by very large numbers of smart people experienced in each business area so don't assume there is fast and easy money to be made. Still, you will be a bit ahead if you learn to read and understand the filings public companies are required to make.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"291903\",\n \"text\": \"\\\"Pink Sheets is not a stock exchange per se, and securities traded through it are not as \\\"\\\"safe\\\"\\\" as the ones on a stock exchange regulated by SEC. Many companies are traded there because they failed to comply with the SEC regulations, or are bankrupt or don't want the level of reporting to the public that the SEC regulations require. Since you're talking about an ADR of a company traded on LSE, it might be much safer that other, \\\"\\\"regular\\\"\\\", securities, but still it means that you're buying an unregulated security (even if it is of a company regulated elsewhere). Notice the volume of trades: mere thousands of dollars per day (in a good day, in some days there are no trades at all). It makes it harder to sell the security when needed. Why not buying at LSE?\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"534734\",\n \"text\": \"\\\"Systemic and well know patterns in sales are priced in to the security. Typically companies with very cyclical earnings like this will issue guidance of earnings per share within a range. These expected earnings are priced in before the earnings are actually booked. If a company meets these expectations the stock will likely stay relatively flat. If the company misses this expectation, the stock, generally, will get slammed. This kind of Wall Street behavior typically mystifies media outlets when a company's stock declines after reporting a record high level of whatever metric. The record high is irrelevant if it misses the expectation. There is no crystal ball but if something is both well known and expected it's already been \\\"\\\"priced in.\\\"\\\" If the well known expected event doesn't occur, maybe it's a new normal.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"220772\",\n \"text\": \"\\\"The following is only an overview and does not contain all of the in-depth reasons why you should look more deeply. When you look at a stock's financials in depth you are looking for warning signs. These may warn of many things but one important thing to look for is ratio and growth rate manipulation. Using several different accounting methods it is possible to make a final report reflect a PE ratio (or any other ratio) that is inconsistent with the realities of the company's position. Earnings manipulation (in the way that Enron in particular manipulated them) is more widespread than you might think as \\\"\\\"earnings smoothing\\\"\\\" is a common way of keeping earnings in line (or smooth) in a recession or a boom. The reason that PE ratio looks so good could well be because professional investors have avoided the stock as there appear to be \\\"\\\"interesting\\\"\\\" (but legal) accounting decisions that are of concern. Another issue that you don't consider is growth. earnings may look good in the current reporting period but may have been stagnant or falling when considered over multiple periods. The low price may indicate falling revenues, earnings and market share that you would not be aware of when taking only your criteria into account. Understanding a firm will also give you an insight into how future news might affect the company. If the company has a lot of debt and market interest rates rise or fall how will that effect their debt, if another company brings out a competing product next week how will it effect the company? How will it effect their bottom line? How much do they rely on a single product line? How likely is it that their flagship product will become obsolete? How would that effect the company? Looking deeply into a company's financial statements will allow you to see any issues in their accounting practices and give you a feel for how they are preforming over time, it will also let you look into their cost of capital and investment decisions. Looking deeply into their products, company structure and how news will effect them will give you an understanding of potential issues that could threaten your investment before they occur. When looking for value you shouldn't just look at part of the value of the company; you wouldn't just look at sales of a single T-shirt range at Wallmart when deciding whether to invest in them. It is exactly the same argument for why you should look at the whole of the company's state when choosing to invest rather than a few small metrics.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"156816\",\n \"text\": \"The cause of incomplete/inaccurate financial data's appearing on free sites is that it is both complicated and expensive to obtain and parse these data. Even within a single country, different pieces of financial data are handled by different authorities. In the US, for example, there is one generally recognized authority for stock prices and volumes (CQS), but a completely different authority for corporate earnings data (SEC). For futures and options data the only authority is each individual exchange. Each of these sources might have a vastly different interface to their data; some may have websites, others may have FTPs, others may have TCP datastreams to which you must subscribe, etc. Now throw in the rest of the world and all their exchanges and regulatory agencies, and you can see how it's a difficult job to gather all this information, parse it on a daily (or more frequent) basis, and check it all for errors. There are some companies (e.g. Bloomberg) whose entire business model is to do the above. They spend tens of millions of dollars per year to support the infrastructure and manpower required to keep such a complex system working, and they charge their consumers a pretty penny in return. Do Google/Yahoo pay for Bloomberg data access just to display information that we then consume for free? Maybe. Maybe they pay for some less expensive reduced data set. Or a data set that is less rigorously checked for errors. Even if they pay for the best data available, there's no guarantee that a company's last earnings report didn't have a glitch in it, or that Bloomberg's latest download from the Canadian Agency for Corporate Dividends and Moose Census-Taking didn't get cut off in the middle, or that the folks at Yahoo built a robust system that can handle a particular file's not arriving on time. Bloomberg has dozens or even hundreds of employees focused on just this one task; Yahoo probably has 5. Moral: If you really need the best available data you must go to the source(s), or you must pay a provider to whom you can then complain when something is wrong. With free data you get what you pay for.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"390529\",\n \"text\": \"\\\"In the US, a private company with less than 500 owners can dictate who can or can't become a shareholder (this is true in general, but I'm sure there are loopholes). Prior to Google's IPO I could not buy shares in Google at any price. The reason Google was \\\"\\\"forced\\\"\\\" to go public is the 500 shareholder rule. At a high level, with 500 shareholders the company is forced to do some extra financial accounting and they no longer can control who owns a share of the company, allowing me to purchase shares of google at that point. At that point, it typically becomes in the companies best interest to go public. See this article about Google approaching the 500 shareholder limit in 2003. Further, Sorkin is not quite correct that \\\"\\\"securities laws mandate that the company go public\\\"\\\" if by \\\"\\\"go public\\\"\\\" we mean list on a stock exchange, available for general purchase. Securities laws mandate what has to be reported in financial reporting and when you have to report it. Securities laws also can dictate restrictions on ownership of stock and if a company can impose their own restrictions. A group of investors cannot force a company onto a stock exchange. If shares of Facebook are already for sale to anyone, then having >500 shareholders will force Facebook to file more paperwork with the SEC, it won't force Facebook onto the NYSE or NASDAQ. When that point is reached, it may be in Facebook's best interest to have an IPO, but they will not be required by law to do so. Update: CNN article discusses likely Facebook IPO in 2012. When companies have more than 500 shareholders, they're required to make significant financial disclosures -- though they can choose to remain private and keep their stock from trading publicly. However, most companies facing mandatory disclosures opt to go public. The Securities and Exchange Commission gives businesses lots of time to prepare for that milestone. Companies have until 120 days after the end of the fiscal year in which they cross the 500-shareholder line to begin making their disclosures. If Facebook tips the scale this year, that gives it until April 2012 to start filing financial reports.\\\"\",\n \"title\": \"\"\n }\n]"}}},{"rowIdx":165,"cells":{"query_id":{"kind":"string","value":"714"},"query":{"kind":"string","value":"Low expression of miR7a does not repress target genes or exert a biological function in testis."},"positive_passages":{"kind":"list like","value":[{"docid":"18421962","text":"Recent studies have reported that competitive endogenous RNAs (ceRNAs) can act as sponges for a microRNA (miRNA) through their binding sites and that changes in ceRNA abundances from individual genes can modulate the activity of miRNAs. Consideration of this hypothesis would benefit from knowing the quantitative relationship between a miRNA and its endogenous target sites. Here, we altered intracellular target site abundance through expression of an miR-122 target in hepatocytes and livers and analyzed the effects on miR-122 target genes. Target repression was released in a threshold-like manner at high target site abundance (≥1.5 × 10(5) added target sites per cell), and this threshold was insensitive to the effective levels of the miRNA. Furthermore, in response to extreme metabolic liver disease models, global target site abundance of hepatocytes did not change sufficiently to affect miRNA-mediated repression. Thus, modulation of miRNA target abundance is unlikely to cause significant effects on gene expression and metabolism through a ceRNA effect.","title":"Assessing the ceRNA hypothesis with quantitative measurements of miRNA and target abundance."}],"string":"[\n {\n \"docid\": \"18421962\",\n \"text\": \"Recent studies have reported that competitive endogenous RNAs (ceRNAs) can act as sponges for a microRNA (miRNA) through their binding sites and that changes in ceRNA abundances from individual genes can modulate the activity of miRNAs. Consideration of this hypothesis would benefit from knowing the quantitative relationship between a miRNA and its endogenous target sites. Here, we altered intracellular target site abundance through expression of an miR-122 target in hepatocytes and livers and analyzed the effects on miR-122 target genes. Target repression was released in a threshold-like manner at high target site abundance (≥1.5 × 10(5) added target sites per cell), and this threshold was insensitive to the effective levels of the miRNA. Furthermore, in response to extreme metabolic liver disease models, global target site abundance of hepatocytes did not change sufficiently to affect miRNA-mediated repression. Thus, modulation of miRNA target abundance is unlikely to cause significant effects on gene expression and metabolism through a ceRNA effect.\",\n \"title\": \"Assessing the ceRNA hypothesis with quantitative measurements of miRNA and target abundance.\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"15635366","text":"L3mbtl2 has been implicated in transcriptional repression and chromatin compaction but its biological function has not been defined. Here we show that disruption of L3mbtl2 results in embryonic lethality with failure of gastrulation. This correlates with compromised proliferation and abnormal differentiation of L3mbtl2(-/-) embryonic stem (ES) cells. L3mbtl2 regulates genes by recruiting a Polycomb Repressive Complex1 (PRC1)-related complex, resembling the previously described E2F6-complex, and including G9A, Hdac1, and Ring1b. The presence of L3mbtl2 at target genes is associated with H3K9 dimethylation, low histone acetylation, and H2AK119 ubiquitination, but the latter is neither dependent on L3mbtl2 nor sufficient for repression. Genome-wide studies revealed that the L3mbtl2-dependent complex predominantly regulates genes not bound by canonical PRC1 and PRC2. However, some developmental regulators are repressed by the combined activity of all three complexes. Together, we have uncovered a highly selective, essential role for an atypical PRC1-family complex in ES cells and early development.","title":"The polycomb group protein L3mbtl2 assembles an atypical PRC1-family complex that is essential in pluripotent stem cells and early development."},{"docid":"6828370","text":"The canonical role of messenger RNA (mRNA) is to deliver protein-coding information to sites of protein synthesis. However, given that microRNAs bind to RNAs, we hypothesized that RNAs could possess a regulatory role that relies on their ability to compete for microRNA binding, independently of their protein-coding function. As a model for the protein-coding-independent role of RNAs, we describe the functional relationship between the mRNAs produced by the PTEN tumour suppressor gene and its pseudogene PTENP1 and the critical consequences of this interaction. We find that PTENP1 is biologically active as it can regulate cellular levels of PTEN and exert a growth-suppressive role. We also show that the PTENP1 locus is selectively lost in human cancer. We extended our analysis to other cancer-related genes that possess pseudogenes, such as oncogenic KRAS. We also demonstrate that the transcripts of protein-coding genes such as PTEN are biologically active. These findings attribute a novel biological role to expressed pseudogenes, as they can regulate coding gene expression, and reveal a non-coding function for mRNAs.","title":"A coding-independent function of gene and pseudogene mRNAs regulates tumour biology"},{"docid":"18895793","text":"The relationship between chromatin structure and gene expression is a subject of intense study. The universal transcriptional activator Gal4 removes promoter nucleosomes as it triggers transcription, but how it does so has remained obscure. The reverse process, repression of transcription, has often been correlated with the presence of nucleosomes. But it is not known whether nucleosomes are required for that effect. A new quantitative assay describes, for any given location, the fraction of DNA molecules in the population that bears a nucleosome at any given instant. This allows us to follow the time courses of nucleosome removal and reformation, in wild-type and mutant cells, upon activation (by galactose) and repression (by glucose) of the GAL genes of yeast. We show that upon being freed of its inhibitor Gal80 by the action of galactose, Gal4 quickly recruits SWI/SNF to the genes, and that nucleosome \"remodeler\" rapidly removes promoter nucleosomes. In the absence of SWI/SNF, Gal4's action also results in nucleosome removal and the activation of transcription, but both processes are significantly delayed. Addition of glucose to cells growing in galactose represses transcription. But if galactose remains present, Gal4 continues to work, recruiting SWI/SNF and maintaining the promoter nucleosome-free despite it being repressed. This requirement for galactose is obviated in a mutant in which Gal4 works constitutively. These results show how an activator's recruiting function can control chromatin structure both during gene activation and repression. Thus, both under activating and repressing conditions, the activator can recruit an enzymatic machine that removes promoter nucleosomes. Our results show that whereas promoter nucleosome removal invariably accompanies activation, reformation of nucleosomes is not required for repression. The finding that there are two routes to nucleosome removal and activation of transcription-one that requires the action of SWI/SNF recruited by the activator, and a slower one that does not-clarifies our understanding of the early events of gene activation, and in particular corrects earlier reports that SWI/SNF plays no role in GAL gene induction. Our finding that chromatin structure is irrelevant for repression as studied here-that is, repression sets in as efficiently whether or not promoter nucleosomes are allowed to reform-contradicts the widely held, but little tested, idea that nucleosomes are required for repression. These findings were made possible by our nucleosome occupancy assay. The assay, we believe, will prove useful in studying other outstanding issues in the field.","title":"Activator Control of Nucleosome Occupancy in Activation and Repression of Transcription"},{"docid":"6820680","text":"MicroRNAs (miRNAs) are short noncoding RNAs that exert posttranscriptional gene silencing and regulate gene expression. In addition to the hundreds of conserved cellular miRNAs that have been identified, miRNAs of viral origin have been isolated and found to modulate both the viral life cycle and the cellular transcriptome. Thus far, detection of virus-derived miRNAs has been largely limited to DNA viruses, suggesting that RNA viruses may be unable to exploit this aspect of transcriptional regulation. Lack of RNA virus-produced miRNAs has been attributed to the replicative constraints that would incur following RNase III processing of a genomic hairpin. To ascertain whether the generation of viral miRNAs is limited to DNA viruses, we investigated whether influenza virus could be designed to deliver functional miRNAs without affecting replication. Here, we describe a modified influenza A virus that expresses cellular microRNA-124 (miR-124). Insertion of the miR-124 hairpin into an intron of the nuclear export protein transcript resulted in endogenous processing and functional miR-124. We demonstrate that a viral RNA genome incorporating a hairpin does not result in segment instability or miRNA-mediated genomic targeting, thereby permitting the virus to produce a miRNA without having a negative impact on viral replication. This work demonstrates that RNA viruses can produce functional miRNAs and suggests that this level of transcriptional regulation may extend beyond DNA viruses.","title":"Engineered RNA viral synthesis of microRNAs."},{"docid":"10024681","text":"Deregulation of microRNA (miRNA) expression can have a critical role in carcinogenesis. Here we show in prostate cancer that miRNA-205 (miR-205) transcription is commonly repressed and the MIR-205 locus is hypermethylated. LOC642587, the MIR-205 host gene of unknown function, is also concordantly inactivated. We show that miR-205 targets mediator 1 (MED1, also called TRAP220 and PPARBP) for transcriptional silencing in normal prostate cells, leading to reduction in MED1 mRNA levels, and in total and active phospho-MED1 protein. Overexpression of miR-205 in prostate cancer cells negatively affects cell viability, consistent with a tumor suppressor function. We found that hypermethylation of the MIR-205 locus was strongly related with a decrease in miR-205 expression and an increase in MED1 expression in primary tumor samples (n=14), when compared with matched normal prostate (n=7). An expanded patient cohort (tumor n=149, matched normal n=30) also showed significant MIR-205 DNA methylation in tumors compared with normal, and MIR-205 hypermethylation is significantly associated with biochemical recurrence (hazard ratio=2.005, 95% confidence interval (1.109, 3.625), P=0.02), in patients with low preoperative prostate specific antigen. In summary, these results suggest that miR-205 is an epigenetically regulated tumor suppressor that targets MED1 and may provide a potential biomarker in prostate cancer management.","title":"Epigenetic-induced repression of microRNA-205 is associated with MED1 activation and a poorer prognosis in localized prostate cancer"},{"docid":"16550075","text":"BCL-6, a transcriptional repressor frequently translocated in lymphomas, regulates germinal center B cell differentiation and inflammation. DNA microarray screening identified genes repressed by BCL-6, including many lymphocyte activation genes, suggesting that BCL-6 modulates B cell receptor signals. BCL-6 repression of two chemokine genes, MIP-1alpha and IP-10, may also attenuate inflammatory responses. Blimp-1, another BCL-6 target, is important for plasmacytic differentiation. Since BCL-6 expression is silenced in plasma cells, repression of blimp-1 by BCL-6 may control plasmacytic differentiation. Indeed, inhibition of BCL-6 function initiated changes indicative of plasmacytic differentiation, including decreased expression of c-Myc and increased expression of the cell cycle inhibitor p27kip1. These data suggest that malignant transformation by BCL-6 involves inhibition of differentiation and enhanced proliferation.","title":"BCL-6 represses genes that function in lymphocyte differentiation, inflammation, and cell cycle control."},{"docid":"23581096","text":"The SRY gene on the mammalian Y chromosome undoubtedly acts to determine testis, but it is still quite unclear how. It was originally supposed that SRY acts directly to activate other genes in the testis-determining pathway. This paper presents an alternative hypothesis that SRY functions indirectly, by interacting with related genes SOX3 (from which SRY evolved) and SOX9 (which appears to be intimately involved in vertebrate gonad differentiation). Specifically, I propose that in females SOX3 inhibits SOX9 function, but in males, SRY inhibits SOX3 and permits SOX9 to enact its testis-determining role. This hypothesis makes testable predictions of the phenotypes of XX and XY individuals with deficiencies or overproduction of any of the three genes, and is able to account for the difficult cases of XX(SRY-) males and transdifferentiation in the absence of SRY. The hypothesis also suggests a way that the dominant SRY sex-determining system of present-day mammals may have evolved from an ancient system relying on SOX3 dosage.","title":"Interactions between SRY and SOX genes in mammalian sex determination."},{"docid":"20028729","text":"Nuclear receptors regulate many biologically important processes in development and homeostasis by their bimodal function as repressors and activators of gene transcription. A finely tuned modulation of the transcriptional activities of nuclear receptors is crucial for determining highly specific and diversified programmes of gene expression. Recent studies have provided insights into the molecular mechanisms that are required to switch between repression and activation functions, the combinatorial roles of the multiple cofactor complexes that are required for mediating transcriptional regulation, and the central question of how several different signalling pathways can be integrated at the nuclear level to achieve specific profiles of gene expression.","title":"Controlling nuclear receptors: the circular logic of cofactor cycles"},{"docid":"2000038","text":"MicroRNAs (miRNAs) are short, highly conserved noncoding RNA molecules that repress gene expression in a sequence-dependent manner. We performed single-cell measurements using quantitative fluorescence microscopy and flow cytometry to monitor a target gene's protein expression in the presence and absence of regulation by miRNA. We find that although the average level of repression is modest, in agreement with previous population-based measurements, the repression among individual cells varies dramatically. In particular, we show that regulation by miRNAs establishes a threshold level of target mRNA below which protein production is highly repressed. Near this threshold, protein expression responds sensitively to target mRNA input, consistent with a mathematical model of molecular titration. These results show that miRNAs can act both as a switch and as a fine-tuner of gene expression.","title":"MicroRNAs can generate thresholds in target gene expression"},{"docid":"6455142","text":"Although regulation of histone methylation is believed to contribute to embryonic stem cell (ESC) self-renewal, the mechanisms remain obscure. We show here that the histone H3 trimethyl lysine 4 (H3K4me3) demethylase, KDM5B, is a downstream Nanog target and critical for ESC self-renewal. Although KDM5B is believed to function as a promoter-bound repressor, we find that it paradoxically functions as an activator of a gene network associated with self-renewal. ChIP-Seq reveals that KDM5B is predominantly targeted to intragenic regions and that it is recruited to H3K36me3 via an interaction with the chromodomain protein MRG15. Depletion of KDM5B or MRG15 increases intragenic H3K4me3, increases cryptic intragenic transcription, and inhibits transcriptional elongation of KDM5B target genes. We propose that KDM5B activates self-renewal-associated gene expression by repressing cryptic initiation and maintaining an H3K4me3 gradient important for productive transcriptional elongation.","title":"KDM5B regulates embryonic stem cell self-renewal and represses cryptic intragenic transcription."},{"docid":"4434951","text":"BACKGROUND Age-associated epigenetic changes are implicated in aging. Notably, age-associated DNA methylation changes comprise a so-called aging \"clock\", a robust biomarker of aging. However, while genetic, dietary and drug interventions can extend lifespan, their impact on the epigenome is uncharacterised. To fill this knowledge gap, we defined age-associated DNA methylation changes at the whole-genome, single-nucleotide level in mouse liver and tested the impact of longevity-promoting interventions, specifically the Ames dwarf Prop1 df/df mutation, calorie restriction and rapamycin. RESULTS In wild-type mice fed an unsupplemented ad libitum diet, age-associated hypomethylation was enriched at super-enhancers in highly expressed genes critical for liver function. Genes harbouring hypomethylated enhancers were enriched for genes that change expression with age. Hypermethylation was enriched at CpG islands marked with bivalent activating and repressing histone modifications and resembled hypermethylation in liver cancer. Age-associated methylation changes are suppressed in Ames dwarf and calorie restricted mice and more selectively and less specifically in rapamycin treated mice. CONCLUSIONS Age-associated hypo- and hypermethylation events occur at distinct regulatory features of the genome. Distinct longevity-promoting interventions, specifically genetic, dietary and drug interventions, suppress some age-associated methylation changes, consistent with the idea that these interventions exert their beneficial effects, in part, by modulation of the epigenome. This study is a foundation to understand the epigenetic contribution to healthy aging and longevity and the molecular basis of the DNA methylation clock.","title":"Diverse interventions that extend mouse lifespan suppress shared age-associated epigenetic changes at critical gene regulatory regions"},{"docid":"15058155","text":"EBI2, aka GPR183, is a G-couple receptor originally identified in 1993 as one of main genes induced in Burkitt's lymphoma cell line BL41 by Epstein-Barr virus (EBV) infection. After it was reported in 2009 that the receptor played a key role in regulating B cell migration and responses, we initiated an effort in looking for its endogenous ligand. In 2011 we and another group reported the identification of 7α, 25-dihydroxyxcholesterol (7α, 25-OHC), an oxysterol, as the likely physiological ligand of EBI2. A few subsequently published studies further elucidated how 7α, 25-OHC bound to EBI2, and how a gradient of 7α, 25-OHC could be generated in vivo and regulated migration, activation, and functions of B cells, T cells, dendritic cells (DCs), monocytes/macrophages, and astrocytes. The identification of 7α, 25-OHC as a G protein-coupled receptor ligand revealed a previously unknown signaling system of oxysterols, a class of molecules which exert profound biological functions. Dysregulation of the synthesis or functions of these molecules is believed to contribute to inflammation and autoimmune diseases, cardiovascular diseases, neurodegenerative diseases, cancer as well as metabolic diseases such as diabetes, obesity, and dyslipidemia. Therefore EBI2 may represent a promising target for therapeutic interventions for human diseases.","title":"7α, 25-dihydroxycholesterol-mediated activation of EBI2 in immune regulation and diseases"},{"docid":"21487212","text":"Ex-FABP, an extracellular fatty acid binding lipocalin, is physiologically expressed by differentiating chicken chondrocytes and myoblasts. Its expression is enhanced after cell treatment with inflammatory stimuli and repressed by anti-inflammatory agents, behaving as an acute phase protein. Chicken liver fragments in culture show enhanced protein expression after bacterial endotoxin treatment. To investigate the biological role of Ex-FABP, we stably transfected proliferating chondrocytes with an expression vector carrying antisense oriented Ex-FABP cDNA. We observed a dramatic loss of cell viability and a strong inhibition of cell proliferation and differentiation. When chondrocytes were transfected with the antisense oriented Ex-FABP cDNA we observed that Ex-FABP down-modulation increased apoptotic cell number. Myoblasts transfected with the same expression vector showed extensive cell death and impaired myotube formation. We suggest that Ex-FABP acts as a constitutive survival protein and that its expression and activation are fundamental to protect chondrocytes from cell death.","title":"Inhibition of cell proliferation and induction of apoptosis by ExFABP gene targeting."},{"docid":"9159495","text":"Expression levels of many microRNAs (miRNAs) change during aging, notably declining globally in a number of organisms and tissues across taxa. However, little is known about the mechanisms or the biological relevance for this change. We investigated the network of genes that controls miRNA transcription and processing during C. elegans aging. We found that miRNA biogenesis genes are highly networked with transcription factors and aging-associated miRNAs. In particular, miR-71, known to influence life span and itself up-regulated during aging, represses alg-1/Argonaute expression post-transcriptionally during aging. Increased ALG-1 abundance in mir-71 loss-of-function mutants led to globally increased miRNA expression. Interestingly, these mutants demonstrated widespread mRNA expression dysregulation and diminished levels of variability both in gene expression and in overall life span. Thus, the progressive molecular decline often thought to be the result of accumulated damage over an organism's life may be partially explained by a miRNA-directed mechanism of age-associated decline.","title":"A microRNA feedback loop regulates global microRNA abundance during aging."},{"docid":"37204802","text":"Jumonji domain-containing 6 (JMJD6) is a member of the Jumonji C domain-containing family of proteins. Compared to other members of the family, the cellular activity of JMJD6 is still not clearly defined and its biological function is still largely unexplored. Here we report that JMJD6 is physically associated with the tumor suppressor p53. We demonstrated that JMJD6 acts as an α-ketoglutarate- and Fe(II)-dependent lysyl hydroxylase to catalyze p53 hydroxylation. We found that p53 indeed exists as a hydroxylated protein in vivo and that the hydroxylation occurs mainly on lysine 382 of p53. We showed that JMJD6 antagonizes p53 acetylation, promotes the association of p53 with its negative regulator MDMX, and represses transcriptional activity of p53. Depletion of JMJD6 enhances p53 transcriptional activity, arrests cells in the G1 phase, promotes cell apoptosis, and sensitizes cells to DNA damaging agent-induced cell death. Importantly, knockdown of JMJD6 represses p53-dependent colon cell proliferation and tumorigenesis in vivo, and significantly, the expression of JMJD6 is markedly up-regulated in various types of human cancer especially in colon cancer, and high nuclear JMJD6 protein is strongly correlated with aggressive clinical behaviors of colon adenocarcinomas. Our results reveal a novel posttranslational modification for p53 and support the pursuit of JMJD6 as a potential biomarker for colon cancer aggressiveness and a potential target for colon cancer intervention.","title":"JMJD6 Promotes Colon Carcinogenesis through Negative Regulation of p53 by Hydroxylation"},{"docid":"14380875","text":"Glucocorticoids repress NFkappaB-mediated activation of proinflammatory genes such as interleukin-8 (IL-8) and ICAM-1. Our experiments suggest that the glucocorticoid receptor (GR) confers this effect by associating through protein-protein interactions with NFkappaB bound at each of these genes. That is, we show that the GR zinc binding region (ZBR), which includes the DNA binding and dimerization functions of the receptor, binds directly to the dimerization domain of the RelA subunit of NFkappaB in vitro and that the ZBR is sufficient to associate with RelA bound at NFkappaB response elements in vivo. Moreover, we demonstrate in vivo and in vitro that GR does not disrupt DNA binding by NFkappaB. In transient transfections, we found that the GR ligand binding domain is essential for repression of NFkappaB but not for association with it and that GR can repress an NFkappaB derivative bearing a heterologous activation domain. We used chromatin immunoprecipitation assays in untransfected A549 cells to infer the mechanism by which the tethered GR represses NFkappaB-activated transcription. As expected, we found that the inflammatory signal TNFalpha stimulated preinitiation complex (PIC) assembly at the IL-8 and ICAM-1 promoters and that the largest subunit of RNA polymerase II (pol II) in those complexes became phosphorylated at serines 2 and 5 in its carboxy-terminal domain (CTD) heptapeptide repeats (YSPTSPS); these modifications are required for transcription initiation. Remarkably, GR did not inhibit PIC assembly under repressing conditions, but rather interfered with phosphorylation of serine 2 of the pol II CTD.","title":"The Glucocorticoid Receptor Inhibits"},{"docid":"43156471","text":"We have conducted a genomewide investigation into the enzymatic specificity, expression profiles, and binding locations of four histone deacetylases (HDACs), representing the three different phylogenetic classes in fission yeast (Schizosaccharomyces pombe). By directly comparing nucleosome density, histone acetylation patterns and HDAC binding in both intergenic and coding regions with gene expression profiles, we found that Sir2 (class III) and Hos2 (class I) have a role in preventing histone loss; Clr6 (class I) is the principal enzyme in promoter-localized repression. Hos2 has an unexpected role in promoting high expression of growth-related genes by deacetylating H4K16Ac in their open reading frames. Clr3 (class II) acts cooperatively with Sir2 throughout the genome, including the silent regions: rDNA, centromeres, mat2/3 and telomeres. The most significant acetylation sites are H3K14Ac for Clr3 and H3K9Ac for Sir2 at their genomic targets. Clr3 also affects subtelomeric regions which contain clustered stress- and meiosis-induced genes. Thus, this combined genomic approach has uncovered different roles for fission yeast HDACs at the silent regions in repression and activation of gene expression.","title":"Genomewide analysis of nucleosome density histone acetylation and HDAC function in fission yeast."},{"docid":"13777706","text":"Polycomb repressor complexes (PRCs) are important chromatin modifiers fundamentally implicated in pluripotency and cancer. Polycomb silencing in embryonic stem cells (ESCs) can be accompanied by active chromatin and primed RNA polymerase II (RNAPII), but the relationship between PRCs and RNAPII remains unclear genome-wide. We mapped PRC repression markers and four RNAPII states in ESCs using ChIP-seq, and found that PRC targets exhibit a range of RNAPII variants. First, developmental PRC targets are bound by unproductive RNAPII (S5p(+)S7p(-)S2p(-)) genome-wide. Sequential ChIP, Ring1B depletion, and genome-wide correlations show that PRCs and RNAPII-S5p physically bind to the same chromatin and functionally synergize. Second, we identify a cohort of genes marked by PRC and elongating RNAPII (S5p(+)S7p(+)S2p(+)); they produce mRNA and protein, and their expression increases upon PRC1 knockdown. We show that this group of PRC targets switches between active and PRC-repressed states within the ESC population, and that many have roles in metabolism.","title":"Polycomb Associates Genome-wide with a Specific RNA Polymerase II Variant, and Regulates Metabolic Genes in ESCs"},{"docid":"18358026","text":"Cancer cells simultaneously harbor global losses and gains in DNA methylation. We demonstrate that inducing cellular oxidative stress by hydrogen peroxide treatment recruits DNA methyltransferase 1 (DNMT1) to damaged chromatin. DNMT1 becomes part of a complex(es) containing DNMT3B and members of the polycomb repressive complex 4. Hydrogen peroxide treatment causes relocalization of these proteins from non-GC-rich to GC-rich areas. Key components are similarly enriched at gene promoters in an in vivo colitis model. Although high-expression genes enriched for members of the complex have histone mark and nascent transcription changes, CpG island-containing low-expression genes gain promoter DNA methylation. Thus, oxidative damage induces formation and relocalization of a silencing complex that may explain cancer-specific aberrant DNA methylation and transcriptional silencing.","title":"Oxidative damage targets complexes containing DNA methyltransferases, SIRT1, and polycomb members to promoter CpG Islands."},{"docid":"9752604","text":"In light of the emerging interplay between redox and metabolic signaling pathways we investigated the potential cross talk between nuclear factor E2-related factor 2 (Nrf2) and AMP-activated kinase (AMPK), central regulators of the cellular redox and energy balance, respectively. Making use of xanthohumol (XN) as an activator of both the AMPK and the Nrf2 signaling pathway we show that AMPK exerts a positive influence on Nrf2/heme oxygenase (HO)-1 signaling in mouse embryonic fibroblasts. Genetic ablation and pharmacological inhibition of AMPK blunts Nrf2-dependent HO-1 expression by XN already at the mRNA level. XN leads to AMPK activation via interference with mitochondrial function and activation of liver kinase B1 as upstream AMPK kinase. The subsequent AMPK-mediated enhancement of the Nrf2/HO-1 response does not depend on inhibition of the mammalian target of rapamycin, inhibition of glycogen synthase kinase 3β, or altered abundance of Nrf2 (total and nuclear). However, reduced endoplasmic reticulum stress was identified and elaborated as a step in the AMPK-augmented Nrf2/HO-1 response. Overall, we shed more light on the hitherto incompletely understood cross talk between the LKB1/AMPK and the Nrf2/HO-1 axis revealing for the first time involvement of the unfolded protein response as an additional player and suggesting tight cooperation between signaling pathways controlling cellular redox, energy, or protein homeostasis.","title":"Activated AMPK boosts the Nrf2/HO-1 signaling axis—A role for the unfolded protein response"},{"docid":"4455466","text":"Recognition of modified histones by ‘reader’ proteins plays a critical role in the regulation of chromatin. H3K36 trimethylation (H3K36me3) is deposited onto the nucleosomes in the transcribed regions after RNA polymerase II elongation. In yeast, this mark in turn recruits epigenetic regulators to reset the chromatin to a relatively repressive state, thus suppressing cryptic transcription. However, much less is known about the role of H3K36me3 in transcription regulation in mammals. This is further complicated by the transcription-coupled incorporation of the histone variant H3.3 in gene bodies. Here we show that the candidate tumour suppressor ZMYND11 specifically recognizes H3K36me3 on H3.3 (H3.3K36me3) and regulates RNA polymerase II elongation. Structural studies show that in addition to the trimethyl-lysine binding by an aromatic cage within the PWWP domain, the H3.3-dependent recognition is mediated by the encapsulation of the H3.3-specific ‘Ser 31’ residue in a composite pocket formed by the tandem bromo–PWWP domains of ZMYND11. Chromatin immunoprecipitation followed by sequencing shows a genome-wide co-localization of ZMYND11 with H3K36me3 and H3.3 in gene bodies, and its occupancy requires the pre-deposition of H3.3K36me3. Although ZMYND11 is associated with highly expressed genes, it functions as an unconventional transcription co-repressor by modulating RNA polymerase II at the elongation stage. ZMYND11 is critical for the repression of a transcriptional program that is essential for tumour cell growth; low expression levels of ZMYND11 in breast cancer patients correlate with worse prognosis. Consistently, overexpression of ZMYND11 suppresses cancer cell growth in vitro and tumour formation in mice. Together, this study identifies ZMYND11 as an H3.3-specific reader of H3K36me3 that links the histone-variant-mediated transcription elongation control to tumour suppression.","title":"ZMYND11 links histone H3.3K36me3 to transcription elongation and tumour suppression"},{"docid":"7645565","text":"Hepatitis B X protein (HBx) plays an essential role in the hepatitis B virus (HBV) replication cycle, but the function of HBx has been elusive until recently. It was recently shown that transcription from the HBV genome (covalently-closed circular DNA, cccDNA) is inhibited by the structural maintenance of chromosome 5/6 complex (Smc5/6), and that a key function of HBx is to redirect the DNA-damage binding protein 1 (DDB1) E3 ubiquitin ligase to target this complex for degradation. By doing so, HBx alleviates transcriptional repression by Smc5/6 and stimulates HBV gene expression. In this review, we discuss in detail how the interplay between HBx and Smc5/6 was identified and characterized. We also discuss what is known regarding the repression of cccDNA transcription by Smc5/6, the timing of HBx expression, and the potential role of HBx in promoting hepatocellular carcinoma (HCC).","title":"Identifying and Characterizing Interplay between Hepatitis B Virus X Protein and Smc5/6"},{"docid":"18882947","text":"The HMG-box factor Tcf1 is required during T-cell development in the thymus and mediates the nuclear response to Wnt signals. Tcf1(-/-) mice have previously been characterized and show developmental blocks at the CD4-CD8- double negative (DN) to CD4+CD8+ double positive transition. Due to the blocks in T-cell development, Tcf1(-/-) mice normally have a very small thymus. Unexpectedly, a large proportion of Tcf1(-/-) mice spontaneously develop thymic lymphomas with 50% of mice developing a thymic lymphoma/leukemia at the age of 16 wk. These lymphomas are clonal, highly metastatic, and paradoxically show high Wnt signaling when crossed with Wnt reporter mice and have high expression of Wnt target genes Lef1 and Axin2. In wild-type thymocytes, Tcf1 is higher expressed than Lef1, with a predominance of Wnt inhibitory isoforms. Loss of Tcf1 as repressor of Lef1 leads to high Wnt activity and is the initiating event in lymphoma development, which is exacerbated by activating Notch1 mutations. Thus, Notch1 and loss of Tcf1 functionally act as collaborating oncogenic events. Tcf1 deficiency predisposes to the development of thymic lymphomas by ectopic up-regulation of Lef1 due to lack of Tcf1 repressive isoforms and frequently by cooperating activating mutations in Notch1. Tcf1 therefore functions as a T-cell-specific tumor suppressor gene, besides its established role as a Wnt responsive transcription factor. Thus, Tcf1 acts as a molecular switch between proliferative and repressive signals during T-lymphocyte development in the thymus.","title":"The Nuclear Effector of Wnt-Signaling, Tcf1, Functions as a T-Cell–Specific Tumor Suppressor for Development of Lymphomas"},{"docid":"23356816","text":"The mammalian A-type cyclin family consists of two members, cyclin A1 (encoded by Ccna1) and cyclin A2 (encoded by Ccna2). Cyclin A2 promotes both G1/S and G2/M transitions, and targeted deletion of Ccna2 in mouse is embryonic lethal. Cyclin A1 is expressed in mice exclusively in the germ cell lineage and is expressed in humans at highest levels in the testis and certain myeloid leukaemia cells. To investigate the role of cyclin A1 and possible redundancy among the cyclins in vivo, we generated mice bearing a null mutation of Ccna1. Ccna1-/- males were sterile due to a block of spermatogenesis before the first meiotic division, whereas females were normal. Meiosis arrest in Ccna1–/– males was associated with increased germ cell apoptosis, desynapsis abnormalities and reduction of Cdc2 kinase activation at the end of meiotic prophase. Cyclin A1 is therefore essential for spermatocyte passage into the first meiotic division in male mice, a function that cannot be complemented by the concurrently expressed B-type cyclins.","title":"Cyclin A1 is required for meiosis in the male mouse"},{"docid":"8909176","text":"Maltose metabolism of baker's yeast (Saccharomyces cerevisiae) in lean dough is negatively influenced by glucose repression, thereby delaying the dough fermentation. To improve maltose metabolism and leavening ability, it is necessary to alleviate glucose repression. The Snf1 protein kinase is well known to be essential for the response to glucose repression and required for transcription of glucose-repressed genes including the maltose-utilization genes (MAL). In this study, the SNF1 overexpression and deletion industrial baker's yeast strains were constructed and characterized in terms of maltose utilization, growth and fermentation characteristics, mRNA levels of MAL genes (MAL62 encoding the maltase and MAL61 encoding the maltose permease) and maltase and maltose permease activities. Our results suggest that overexpression of SNF1 was effective to glucose derepression for enhancing MAL expression levels and enzymes (maltase and maltose permease) activities. These enhancements could result in an 18% increase in maltose metabolism of industrial baker's yeast in LSMLD medium (the low sugar model liquid dough fermentation medium) containing glucose and maltose and a 15% increase in leavening ability in lean dough. These findings provide a valuable insight of breeding industrial baker's yeast for rapid fermentation.","title":"Effects of SNF1 on Maltose Metabolism and Leavening Ability of Baker's Yeast in Lean Dough."},{"docid":"8331432","text":"The transcription factor HNF3 and linker histones H1 and H5 possess winged-helix DNA-binding domains, yet HNF3 and other fork head-related proteins activate genes during development whereas linker histones compact DNA in chromatin and repress gene expression. We compared how the two classes of factors interact with chromatin templates and found that HNF3 binds DNA at the side of nucleosome cores, similarly to what has been reported for linker histone. A nucleosome structural binding site for HNF3 is occupied at the albumin transcriptional enhancer in active and potentially active chromatin, but not in inactive chromatin in vivo. While wild-type HNF3 protein does not compact DNA extending from the nucleosome, as does linker histone, site-directed mutants of HNF3 can compact nucleosomal DNA if they contain basic amino acids at positions previously shown to be essential for nucleosomal DNA compaction by linker histones. The results illustrate how transcription factors can possess special nucleosome-binding activities that are not predicted from studies of factor interactions with free DNA.","title":"Binding of the winged-helix transcription factor HNF3 to a linker histone site on the nucleosome."},{"docid":"12652963","text":"MicroRNAs (miRNAs) are ∼22 nt non-coding RNAs that typically bind to the 3' UTR of target mRNAs in the cytoplasm, resulting in mRNA destabilization and translational repression. Here, we report that miRNAs can also regulate gene expression by targeting non-coding antisense transcripts in human cells. Specifically, we show that miR-671 directs cleavage of a circular antisense transcript of the Cerebellar Degeneration-Related protein 1 (CDR1) locus in an Ago2-slicer-dependent manner. The resulting downregulation of circular antisense has a concomitant decrease in CDR1 mRNA levels, independently of heterochromatin formation. This study provides the first evidence for non-coding antisense transcripts as functional miRNA targets, and a novel regulatory mechanism involving a positive correlation between mRNA and antisense circular RNA levels.","title":"miRNA-dependent gene silencing involving Ago2-mediated cleavage of a circular antisense RNA."},{"docid":"37438296","text":"Age-dependent decline in skeletal muscle function leads to several inherited and acquired muscular disorders in elderly individuals. The levels of microRNAs (miRNAs) could be altered during muscle maintenance and repair. We therefore performed a comprehensive investigation for miRNAs from five different periods of bovine skeletal muscle development using next-generation small RNA sequencing. In total, 511 miRNAs, including one putatively novel miRNA, were identified. Thirty-six miRNAs were differentially expressed between prenatal and postnatal stages of muscle development including several myomiRs (miR-1, miR-206 and let-7 families). Compared with miRNA expression between different muscle tissues, 14 miRNAs were up-regulated and 22 miRNAs were down-regulated in the muscle of postnatal stage. In addition, a novel miRNA was predicted and submitted to the miRBase database as bta-mir-10020. A dual luciferase reporter assay was used to demonstrate that bta-mir-10020 directly targeted the 3'-UTR of the bovine ANGPT1 gene. The overexpression of bta-mir-10020 significantly decreased the DsRed fluorescence in the wild-type expression cassette compared to the mutant type. Using three computational approaches - miranda, pita and rnahybrid - these differentially expressed miRNAs were also predicted to target 3609 bovine genes. Disease and biological function analyses and the KEGG pathway analysis revealed that these targets were statistically enriched in functionality for muscle growth and disease. Our miRNA expression analysis findings from different states of muscle development and aging significantly expand the repertoire of bovine miRNAs now shown to be expressed in muscle and could contribute to further studies on growth and developmental disorders in this tissue type.","title":"Altered microRNA expression in bovine skeletal muscle with age."},{"docid":"27949347","text":"TP53 is the most frequently mutated gene in human cancer. Functionally, p53 is activated by a host of stress stimuli and, in turn, governs an exquisitely complex anti-proliferative transcriptional program that touches upon a bewildering array of biological responses. Despite the many unveiled facets of the p53 network, a clear appreciation of how and in what contexts p53 exerts its diverse effects remains unclear. How can we interpret p53's disparate activities and the consequences of its dysfunction to understand how cell type, mutation profile, and epigenetic cell state dictate outcomes, and how might we restore its tumor-suppressive activities in cancer?","title":"Putting p53 in Context"},{"docid":"31882215","text":"We describe robust induction of autophagy during the reprogramming of mouse fibroblasts to induced pluripotent stem cells by four reprogramming factors (Sox2, Oct4, Klf4 and c-Myc), henceforth 4F. This process occurs independently of p53 activation, and is mediated by the synergistic downregulation of mechanistic target of rapamycin complex 1 (mTORC1) and the induction of autophagy-related genes. The 4F coordinately repress mTORC1, but bifurcate in their regulation of autophagy-related genes, with Klf4 and c-Myc inducing them but Sox2 and Oct4 inhibiting them. On one hand, inhibition of mTORC1 facilitates reprogramming by promoting cell reshaping (mitochondrial remodelling and cell size reduction). On the other hand, mTORC1 paradoxically impairs reprogramming by triggering autophagy. Autophagy does not participate in cell reshaping in reprogramming but instead degrades p62, whose accumulation in autophagy-deficient cells facilitates reprogramming. Our results thus reveal a complex signalling network involving mTORC1 inhibition and autophagy induction in the early phase of reprogramming, whose delicate balance ultimately determines reprogramming efficiency.","title":"Autophagy and mTORC1 regulate the stochastic phase of somatic cell reprogramming"}],"string":"[\n {\n \"docid\": \"15635366\",\n \"text\": \"L3mbtl2 has been implicated in transcriptional repression and chromatin compaction but its biological function has not been defined. Here we show that disruption of L3mbtl2 results in embryonic lethality with failure of gastrulation. This correlates with compromised proliferation and abnormal differentiation of L3mbtl2(-/-) embryonic stem (ES) cells. L3mbtl2 regulates genes by recruiting a Polycomb Repressive Complex1 (PRC1)-related complex, resembling the previously described E2F6-complex, and including G9A, Hdac1, and Ring1b. The presence of L3mbtl2 at target genes is associated with H3K9 dimethylation, low histone acetylation, and H2AK119 ubiquitination, but the latter is neither dependent on L3mbtl2 nor sufficient for repression. Genome-wide studies revealed that the L3mbtl2-dependent complex predominantly regulates genes not bound by canonical PRC1 and PRC2. However, some developmental regulators are repressed by the combined activity of all three complexes. Together, we have uncovered a highly selective, essential role for an atypical PRC1-family complex in ES cells and early development.\",\n \"title\": \"The polycomb group protein L3mbtl2 assembles an atypical PRC1-family complex that is essential in pluripotent stem cells and early development.\"\n },\n {\n \"docid\": \"6828370\",\n \"text\": \"The canonical role of messenger RNA (mRNA) is to deliver protein-coding information to sites of protein synthesis. However, given that microRNAs bind to RNAs, we hypothesized that RNAs could possess a regulatory role that relies on their ability to compete for microRNA binding, independently of their protein-coding function. As a model for the protein-coding-independent role of RNAs, we describe the functional relationship between the mRNAs produced by the PTEN tumour suppressor gene and its pseudogene PTENP1 and the critical consequences of this interaction. We find that PTENP1 is biologically active as it can regulate cellular levels of PTEN and exert a growth-suppressive role. We also show that the PTENP1 locus is selectively lost in human cancer. We extended our analysis to other cancer-related genes that possess pseudogenes, such as oncogenic KRAS. We also demonstrate that the transcripts of protein-coding genes such as PTEN are biologically active. These findings attribute a novel biological role to expressed pseudogenes, as they can regulate coding gene expression, and reveal a non-coding function for mRNAs.\",\n \"title\": \"A coding-independent function of gene and pseudogene mRNAs regulates tumour biology\"\n },\n {\n \"docid\": \"18895793\",\n \"text\": \"The relationship between chromatin structure and gene expression is a subject of intense study. The universal transcriptional activator Gal4 removes promoter nucleosomes as it triggers transcription, but how it does so has remained obscure. The reverse process, repression of transcription, has often been correlated with the presence of nucleosomes. But it is not known whether nucleosomes are required for that effect. A new quantitative assay describes, for any given location, the fraction of DNA molecules in the population that bears a nucleosome at any given instant. This allows us to follow the time courses of nucleosome removal and reformation, in wild-type and mutant cells, upon activation (by galactose) and repression (by glucose) of the GAL genes of yeast. We show that upon being freed of its inhibitor Gal80 by the action of galactose, Gal4 quickly recruits SWI/SNF to the genes, and that nucleosome \\\"remodeler\\\" rapidly removes promoter nucleosomes. In the absence of SWI/SNF, Gal4's action also results in nucleosome removal and the activation of transcription, but both processes are significantly delayed. Addition of glucose to cells growing in galactose represses transcription. But if galactose remains present, Gal4 continues to work, recruiting SWI/SNF and maintaining the promoter nucleosome-free despite it being repressed. This requirement for galactose is obviated in a mutant in which Gal4 works constitutively. These results show how an activator's recruiting function can control chromatin structure both during gene activation and repression. Thus, both under activating and repressing conditions, the activator can recruit an enzymatic machine that removes promoter nucleosomes. Our results show that whereas promoter nucleosome removal invariably accompanies activation, reformation of nucleosomes is not required for repression. The finding that there are two routes to nucleosome removal and activation of transcription-one that requires the action of SWI/SNF recruited by the activator, and a slower one that does not-clarifies our understanding of the early events of gene activation, and in particular corrects earlier reports that SWI/SNF plays no role in GAL gene induction. Our finding that chromatin structure is irrelevant for repression as studied here-that is, repression sets in as efficiently whether or not promoter nucleosomes are allowed to reform-contradicts the widely held, but little tested, idea that nucleosomes are required for repression. These findings were made possible by our nucleosome occupancy assay. The assay, we believe, will prove useful in studying other outstanding issues in the field.\",\n \"title\": \"Activator Control of Nucleosome Occupancy in Activation and Repression of Transcription\"\n },\n {\n \"docid\": \"6820680\",\n \"text\": \"MicroRNAs (miRNAs) are short noncoding RNAs that exert posttranscriptional gene silencing and regulate gene expression. In addition to the hundreds of conserved cellular miRNAs that have been identified, miRNAs of viral origin have been isolated and found to modulate both the viral life cycle and the cellular transcriptome. Thus far, detection of virus-derived miRNAs has been largely limited to DNA viruses, suggesting that RNA viruses may be unable to exploit this aspect of transcriptional regulation. Lack of RNA virus-produced miRNAs has been attributed to the replicative constraints that would incur following RNase III processing of a genomic hairpin. To ascertain whether the generation of viral miRNAs is limited to DNA viruses, we investigated whether influenza virus could be designed to deliver functional miRNAs without affecting replication. Here, we describe a modified influenza A virus that expresses cellular microRNA-124 (miR-124). Insertion of the miR-124 hairpin into an intron of the nuclear export protein transcript resulted in endogenous processing and functional miR-124. We demonstrate that a viral RNA genome incorporating a hairpin does not result in segment instability or miRNA-mediated genomic targeting, thereby permitting the virus to produce a miRNA without having a negative impact on viral replication. This work demonstrates that RNA viruses can produce functional miRNAs and suggests that this level of transcriptional regulation may extend beyond DNA viruses.\",\n \"title\": \"Engineered RNA viral synthesis of microRNAs.\"\n },\n {\n \"docid\": \"10024681\",\n \"text\": \"Deregulation of microRNA (miRNA) expression can have a critical role in carcinogenesis. Here we show in prostate cancer that miRNA-205 (miR-205) transcription is commonly repressed and the MIR-205 locus is hypermethylated. LOC642587, the MIR-205 host gene of unknown function, is also concordantly inactivated. We show that miR-205 targets mediator 1 (MED1, also called TRAP220 and PPARBP) for transcriptional silencing in normal prostate cells, leading to reduction in MED1 mRNA levels, and in total and active phospho-MED1 protein. Overexpression of miR-205 in prostate cancer cells negatively affects cell viability, consistent with a tumor suppressor function. We found that hypermethylation of the MIR-205 locus was strongly related with a decrease in miR-205 expression and an increase in MED1 expression in primary tumor samples (n=14), when compared with matched normal prostate (n=7). An expanded patient cohort (tumor n=149, matched normal n=30) also showed significant MIR-205 DNA methylation in tumors compared with normal, and MIR-205 hypermethylation is significantly associated with biochemical recurrence (hazard ratio=2.005, 95% confidence interval (1.109, 3.625), P=0.02), in patients with low preoperative prostate specific antigen. In summary, these results suggest that miR-205 is an epigenetically regulated tumor suppressor that targets MED1 and may provide a potential biomarker in prostate cancer management.\",\n \"title\": \"Epigenetic-induced repression of microRNA-205 is associated with MED1 activation and a poorer prognosis in localized prostate cancer\"\n },\n {\n \"docid\": \"16550075\",\n \"text\": \"BCL-6, a transcriptional repressor frequently translocated in lymphomas, regulates germinal center B cell differentiation and inflammation. DNA microarray screening identified genes repressed by BCL-6, including many lymphocyte activation genes, suggesting that BCL-6 modulates B cell receptor signals. BCL-6 repression of two chemokine genes, MIP-1alpha and IP-10, may also attenuate inflammatory responses. Blimp-1, another BCL-6 target, is important for plasmacytic differentiation. Since BCL-6 expression is silenced in plasma cells, repression of blimp-1 by BCL-6 may control plasmacytic differentiation. Indeed, inhibition of BCL-6 function initiated changes indicative of plasmacytic differentiation, including decreased expression of c-Myc and increased expression of the cell cycle inhibitor p27kip1. These data suggest that malignant transformation by BCL-6 involves inhibition of differentiation and enhanced proliferation.\",\n \"title\": \"BCL-6 represses genes that function in lymphocyte differentiation, inflammation, and cell cycle control.\"\n },\n {\n \"docid\": \"23581096\",\n \"text\": \"The SRY gene on the mammalian Y chromosome undoubtedly acts to determine testis, but it is still quite unclear how. It was originally supposed that SRY acts directly to activate other genes in the testis-determining pathway. This paper presents an alternative hypothesis that SRY functions indirectly, by interacting with related genes SOX3 (from which SRY evolved) and SOX9 (which appears to be intimately involved in vertebrate gonad differentiation). Specifically, I propose that in females SOX3 inhibits SOX9 function, but in males, SRY inhibits SOX3 and permits SOX9 to enact its testis-determining role. This hypothesis makes testable predictions of the phenotypes of XX and XY individuals with deficiencies or overproduction of any of the three genes, and is able to account for the difficult cases of XX(SRY-) males and transdifferentiation in the absence of SRY. The hypothesis also suggests a way that the dominant SRY sex-determining system of present-day mammals may have evolved from an ancient system relying on SOX3 dosage.\",\n \"title\": \"Interactions between SRY and SOX genes in mammalian sex determination.\"\n },\n {\n \"docid\": \"20028729\",\n \"text\": \"Nuclear receptors regulate many biologically important processes in development and homeostasis by their bimodal function as repressors and activators of gene transcription. A finely tuned modulation of the transcriptional activities of nuclear receptors is crucial for determining highly specific and diversified programmes of gene expression. Recent studies have provided insights into the molecular mechanisms that are required to switch between repression and activation functions, the combinatorial roles of the multiple cofactor complexes that are required for mediating transcriptional regulation, and the central question of how several different signalling pathways can be integrated at the nuclear level to achieve specific profiles of gene expression.\",\n \"title\": \"Controlling nuclear receptors: the circular logic of cofactor cycles\"\n },\n {\n \"docid\": \"2000038\",\n \"text\": \"MicroRNAs (miRNAs) are short, highly conserved noncoding RNA molecules that repress gene expression in a sequence-dependent manner. We performed single-cell measurements using quantitative fluorescence microscopy and flow cytometry to monitor a target gene's protein expression in the presence and absence of regulation by miRNA. We find that although the average level of repression is modest, in agreement with previous population-based measurements, the repression among individual cells varies dramatically. In particular, we show that regulation by miRNAs establishes a threshold level of target mRNA below which protein production is highly repressed. Near this threshold, protein expression responds sensitively to target mRNA input, consistent with a mathematical model of molecular titration. These results show that miRNAs can act both as a switch and as a fine-tuner of gene expression.\",\n \"title\": \"MicroRNAs can generate thresholds in target gene expression\"\n },\n {\n \"docid\": \"6455142\",\n \"text\": \"Although regulation of histone methylation is believed to contribute to embryonic stem cell (ESC) self-renewal, the mechanisms remain obscure. We show here that the histone H3 trimethyl lysine 4 (H3K4me3) demethylase, KDM5B, is a downstream Nanog target and critical for ESC self-renewal. Although KDM5B is believed to function as a promoter-bound repressor, we find that it paradoxically functions as an activator of a gene network associated with self-renewal. ChIP-Seq reveals that KDM5B is predominantly targeted to intragenic regions and that it is recruited to H3K36me3 via an interaction with the chromodomain protein MRG15. Depletion of KDM5B or MRG15 increases intragenic H3K4me3, increases cryptic intragenic transcription, and inhibits transcriptional elongation of KDM5B target genes. We propose that KDM5B activates self-renewal-associated gene expression by repressing cryptic initiation and maintaining an H3K4me3 gradient important for productive transcriptional elongation.\",\n \"title\": \"KDM5B regulates embryonic stem cell self-renewal and represses cryptic intragenic transcription.\"\n },\n {\n \"docid\": \"4434951\",\n \"text\": \"BACKGROUND Age-associated epigenetic changes are implicated in aging. Notably, age-associated DNA methylation changes comprise a so-called aging \\\"clock\\\", a robust biomarker of aging. However, while genetic, dietary and drug interventions can extend lifespan, their impact on the epigenome is uncharacterised. To fill this knowledge gap, we defined age-associated DNA methylation changes at the whole-genome, single-nucleotide level in mouse liver and tested the impact of longevity-promoting interventions, specifically the Ames dwarf Prop1 df/df mutation, calorie restriction and rapamycin. RESULTS In wild-type mice fed an unsupplemented ad libitum diet, age-associated hypomethylation was enriched at super-enhancers in highly expressed genes critical for liver function. Genes harbouring hypomethylated enhancers were enriched for genes that change expression with age. Hypermethylation was enriched at CpG islands marked with bivalent activating and repressing histone modifications and resembled hypermethylation in liver cancer. Age-associated methylation changes are suppressed in Ames dwarf and calorie restricted mice and more selectively and less specifically in rapamycin treated mice. CONCLUSIONS Age-associated hypo- and hypermethylation events occur at distinct regulatory features of the genome. Distinct longevity-promoting interventions, specifically genetic, dietary and drug interventions, suppress some age-associated methylation changes, consistent with the idea that these interventions exert their beneficial effects, in part, by modulation of the epigenome. This study is a foundation to understand the epigenetic contribution to healthy aging and longevity and the molecular basis of the DNA methylation clock.\",\n \"title\": \"Diverse interventions that extend mouse lifespan suppress shared age-associated epigenetic changes at critical gene regulatory regions\"\n },\n {\n \"docid\": \"15058155\",\n \"text\": \"EBI2, aka GPR183, is a G-couple receptor originally identified in 1993 as one of main genes induced in Burkitt's lymphoma cell line BL41 by Epstein-Barr virus (EBV) infection. After it was reported in 2009 that the receptor played a key role in regulating B cell migration and responses, we initiated an effort in looking for its endogenous ligand. In 2011 we and another group reported the identification of 7α, 25-dihydroxyxcholesterol (7α, 25-OHC), an oxysterol, as the likely physiological ligand of EBI2. A few subsequently published studies further elucidated how 7α, 25-OHC bound to EBI2, and how a gradient of 7α, 25-OHC could be generated in vivo and regulated migration, activation, and functions of B cells, T cells, dendritic cells (DCs), monocytes/macrophages, and astrocytes. The identification of 7α, 25-OHC as a G protein-coupled receptor ligand revealed a previously unknown signaling system of oxysterols, a class of molecules which exert profound biological functions. Dysregulation of the synthesis or functions of these molecules is believed to contribute to inflammation and autoimmune diseases, cardiovascular diseases, neurodegenerative diseases, cancer as well as metabolic diseases such as diabetes, obesity, and dyslipidemia. Therefore EBI2 may represent a promising target for therapeutic interventions for human diseases.\",\n \"title\": \"7α, 25-dihydroxycholesterol-mediated activation of EBI2 in immune regulation and diseases\"\n },\n {\n \"docid\": \"21487212\",\n \"text\": \"Ex-FABP, an extracellular fatty acid binding lipocalin, is physiologically expressed by differentiating chicken chondrocytes and myoblasts. Its expression is enhanced after cell treatment with inflammatory stimuli and repressed by anti-inflammatory agents, behaving as an acute phase protein. Chicken liver fragments in culture show enhanced protein expression after bacterial endotoxin treatment. To investigate the biological role of Ex-FABP, we stably transfected proliferating chondrocytes with an expression vector carrying antisense oriented Ex-FABP cDNA. We observed a dramatic loss of cell viability and a strong inhibition of cell proliferation and differentiation. When chondrocytes were transfected with the antisense oriented Ex-FABP cDNA we observed that Ex-FABP down-modulation increased apoptotic cell number. Myoblasts transfected with the same expression vector showed extensive cell death and impaired myotube formation. We suggest that Ex-FABP acts as a constitutive survival protein and that its expression and activation are fundamental to protect chondrocytes from cell death.\",\n \"title\": \"Inhibition of cell proliferation and induction of apoptosis by ExFABP gene targeting.\"\n },\n {\n \"docid\": \"9159495\",\n \"text\": \"Expression levels of many microRNAs (miRNAs) change during aging, notably declining globally in a number of organisms and tissues across taxa. However, little is known about the mechanisms or the biological relevance for this change. We investigated the network of genes that controls miRNA transcription and processing during C. elegans aging. We found that miRNA biogenesis genes are highly networked with transcription factors and aging-associated miRNAs. In particular, miR-71, known to influence life span and itself up-regulated during aging, represses alg-1/Argonaute expression post-transcriptionally during aging. Increased ALG-1 abundance in mir-71 loss-of-function mutants led to globally increased miRNA expression. Interestingly, these mutants demonstrated widespread mRNA expression dysregulation and diminished levels of variability both in gene expression and in overall life span. Thus, the progressive molecular decline often thought to be the result of accumulated damage over an organism's life may be partially explained by a miRNA-directed mechanism of age-associated decline.\",\n \"title\": \"A microRNA feedback loop regulates global microRNA abundance during aging.\"\n },\n {\n \"docid\": \"37204802\",\n \"text\": \"Jumonji domain-containing 6 (JMJD6) is a member of the Jumonji C domain-containing family of proteins. Compared to other members of the family, the cellular activity of JMJD6 is still not clearly defined and its biological function is still largely unexplored. Here we report that JMJD6 is physically associated with the tumor suppressor p53. We demonstrated that JMJD6 acts as an α-ketoglutarate- and Fe(II)-dependent lysyl hydroxylase to catalyze p53 hydroxylation. We found that p53 indeed exists as a hydroxylated protein in vivo and that the hydroxylation occurs mainly on lysine 382 of p53. We showed that JMJD6 antagonizes p53 acetylation, promotes the association of p53 with its negative regulator MDMX, and represses transcriptional activity of p53. Depletion of JMJD6 enhances p53 transcriptional activity, arrests cells in the G1 phase, promotes cell apoptosis, and sensitizes cells to DNA damaging agent-induced cell death. Importantly, knockdown of JMJD6 represses p53-dependent colon cell proliferation and tumorigenesis in vivo, and significantly, the expression of JMJD6 is markedly up-regulated in various types of human cancer especially in colon cancer, and high nuclear JMJD6 protein is strongly correlated with aggressive clinical behaviors of colon adenocarcinomas. Our results reveal a novel posttranslational modification for p53 and support the pursuit of JMJD6 as a potential biomarker for colon cancer aggressiveness and a potential target for colon cancer intervention.\",\n \"title\": \"JMJD6 Promotes Colon Carcinogenesis through Negative Regulation of p53 by Hydroxylation\"\n },\n {\n \"docid\": \"14380875\",\n \"text\": \"Glucocorticoids repress NFkappaB-mediated activation of proinflammatory genes such as interleukin-8 (IL-8) and ICAM-1. Our experiments suggest that the glucocorticoid receptor (GR) confers this effect by associating through protein-protein interactions with NFkappaB bound at each of these genes. That is, we show that the GR zinc binding region (ZBR), which includes the DNA binding and dimerization functions of the receptor, binds directly to the dimerization domain of the RelA subunit of NFkappaB in vitro and that the ZBR is sufficient to associate with RelA bound at NFkappaB response elements in vivo. Moreover, we demonstrate in vivo and in vitro that GR does not disrupt DNA binding by NFkappaB. In transient transfections, we found that the GR ligand binding domain is essential for repression of NFkappaB but not for association with it and that GR can repress an NFkappaB derivative bearing a heterologous activation domain. We used chromatin immunoprecipitation assays in untransfected A549 cells to infer the mechanism by which the tethered GR represses NFkappaB-activated transcription. As expected, we found that the inflammatory signal TNFalpha stimulated preinitiation complex (PIC) assembly at the IL-8 and ICAM-1 promoters and that the largest subunit of RNA polymerase II (pol II) in those complexes became phosphorylated at serines 2 and 5 in its carboxy-terminal domain (CTD) heptapeptide repeats (YSPTSPS); these modifications are required for transcription initiation. Remarkably, GR did not inhibit PIC assembly under repressing conditions, but rather interfered with phosphorylation of serine 2 of the pol II CTD.\",\n \"title\": \"The Glucocorticoid Receptor Inhibits\"\n },\n {\n \"docid\": \"43156471\",\n \"text\": \"We have conducted a genomewide investigation into the enzymatic specificity, expression profiles, and binding locations of four histone deacetylases (HDACs), representing the three different phylogenetic classes in fission yeast (Schizosaccharomyces pombe). By directly comparing nucleosome density, histone acetylation patterns and HDAC binding in both intergenic and coding regions with gene expression profiles, we found that Sir2 (class III) and Hos2 (class I) have a role in preventing histone loss; Clr6 (class I) is the principal enzyme in promoter-localized repression. Hos2 has an unexpected role in promoting high expression of growth-related genes by deacetylating H4K16Ac in their open reading frames. Clr3 (class II) acts cooperatively with Sir2 throughout the genome, including the silent regions: rDNA, centromeres, mat2/3 and telomeres. The most significant acetylation sites are H3K14Ac for Clr3 and H3K9Ac for Sir2 at their genomic targets. Clr3 also affects subtelomeric regions which contain clustered stress- and meiosis-induced genes. Thus, this combined genomic approach has uncovered different roles for fission yeast HDACs at the silent regions in repression and activation of gene expression.\",\n \"title\": \"Genomewide analysis of nucleosome density histone acetylation and HDAC function in fission yeast.\"\n },\n {\n \"docid\": \"13777706\",\n \"text\": \"Polycomb repressor complexes (PRCs) are important chromatin modifiers fundamentally implicated in pluripotency and cancer. Polycomb silencing in embryonic stem cells (ESCs) can be accompanied by active chromatin and primed RNA polymerase II (RNAPII), but the relationship between PRCs and RNAPII remains unclear genome-wide. We mapped PRC repression markers and four RNAPII states in ESCs using ChIP-seq, and found that PRC targets exhibit a range of RNAPII variants. First, developmental PRC targets are bound by unproductive RNAPII (S5p(+)S7p(-)S2p(-)) genome-wide. Sequential ChIP, Ring1B depletion, and genome-wide correlations show that PRCs and RNAPII-S5p physically bind to the same chromatin and functionally synergize. Second, we identify a cohort of genes marked by PRC and elongating RNAPII (S5p(+)S7p(+)S2p(+)); they produce mRNA and protein, and their expression increases upon PRC1 knockdown. We show that this group of PRC targets switches between active and PRC-repressed states within the ESC population, and that many have roles in metabolism.\",\n \"title\": \"Polycomb Associates Genome-wide with a Specific RNA Polymerase II Variant, and Regulates Metabolic Genes in ESCs\"\n },\n {\n \"docid\": \"18358026\",\n \"text\": \"Cancer cells simultaneously harbor global losses and gains in DNA methylation. We demonstrate that inducing cellular oxidative stress by hydrogen peroxide treatment recruits DNA methyltransferase 1 (DNMT1) to damaged chromatin. DNMT1 becomes part of a complex(es) containing DNMT3B and members of the polycomb repressive complex 4. Hydrogen peroxide treatment causes relocalization of these proteins from non-GC-rich to GC-rich areas. Key components are similarly enriched at gene promoters in an in vivo colitis model. Although high-expression genes enriched for members of the complex have histone mark and nascent transcription changes, CpG island-containing low-expression genes gain promoter DNA methylation. Thus, oxidative damage induces formation and relocalization of a silencing complex that may explain cancer-specific aberrant DNA methylation and transcriptional silencing.\",\n \"title\": \"Oxidative damage targets complexes containing DNA methyltransferases, SIRT1, and polycomb members to promoter CpG Islands.\"\n },\n {\n \"docid\": \"9752604\",\n \"text\": \"In light of the emerging interplay between redox and metabolic signaling pathways we investigated the potential cross talk between nuclear factor E2-related factor 2 (Nrf2) and AMP-activated kinase (AMPK), central regulators of the cellular redox and energy balance, respectively. Making use of xanthohumol (XN) as an activator of both the AMPK and the Nrf2 signaling pathway we show that AMPK exerts a positive influence on Nrf2/heme oxygenase (HO)-1 signaling in mouse embryonic fibroblasts. Genetic ablation and pharmacological inhibition of AMPK blunts Nrf2-dependent HO-1 expression by XN already at the mRNA level. XN leads to AMPK activation via interference with mitochondrial function and activation of liver kinase B1 as upstream AMPK kinase. The subsequent AMPK-mediated enhancement of the Nrf2/HO-1 response does not depend on inhibition of the mammalian target of rapamycin, inhibition of glycogen synthase kinase 3β, or altered abundance of Nrf2 (total and nuclear). However, reduced endoplasmic reticulum stress was identified and elaborated as a step in the AMPK-augmented Nrf2/HO-1 response. Overall, we shed more light on the hitherto incompletely understood cross talk between the LKB1/AMPK and the Nrf2/HO-1 axis revealing for the first time involvement of the unfolded protein response as an additional player and suggesting tight cooperation between signaling pathways controlling cellular redox, energy, or protein homeostasis.\",\n \"title\": \"Activated AMPK boosts the Nrf2/HO-1 signaling axis—A role for the unfolded protein response\"\n },\n {\n \"docid\": \"4455466\",\n \"text\": \"Recognition of modified histones by ‘reader’ proteins plays a critical role in the regulation of chromatin. H3K36 trimethylation (H3K36me3) is deposited onto the nucleosomes in the transcribed regions after RNA polymerase II elongation. In yeast, this mark in turn recruits epigenetic regulators to reset the chromatin to a relatively repressive state, thus suppressing cryptic transcription. However, much less is known about the role of H3K36me3 in transcription regulation in mammals. This is further complicated by the transcription-coupled incorporation of the histone variant H3.3 in gene bodies. Here we show that the candidate tumour suppressor ZMYND11 specifically recognizes H3K36me3 on H3.3 (H3.3K36me3) and regulates RNA polymerase II elongation. Structural studies show that in addition to the trimethyl-lysine binding by an aromatic cage within the PWWP domain, the H3.3-dependent recognition is mediated by the encapsulation of the H3.3-specific ‘Ser 31’ residue in a composite pocket formed by the tandem bromo–PWWP domains of ZMYND11. Chromatin immunoprecipitation followed by sequencing shows a genome-wide co-localization of ZMYND11 with H3K36me3 and H3.3 in gene bodies, and its occupancy requires the pre-deposition of H3.3K36me3. Although ZMYND11 is associated with highly expressed genes, it functions as an unconventional transcription co-repressor by modulating RNA polymerase II at the elongation stage. ZMYND11 is critical for the repression of a transcriptional program that is essential for tumour cell growth; low expression levels of ZMYND11 in breast cancer patients correlate with worse prognosis. Consistently, overexpression of ZMYND11 suppresses cancer cell growth in vitro and tumour formation in mice. Together, this study identifies ZMYND11 as an H3.3-specific reader of H3K36me3 that links the histone-variant-mediated transcription elongation control to tumour suppression.\",\n \"title\": \"ZMYND11 links histone H3.3K36me3 to transcription elongation and tumour suppression\"\n },\n {\n \"docid\": \"7645565\",\n \"text\": \"Hepatitis B X protein (HBx) plays an essential role in the hepatitis B virus (HBV) replication cycle, but the function of HBx has been elusive until recently. It was recently shown that transcription from the HBV genome (covalently-closed circular DNA, cccDNA) is inhibited by the structural maintenance of chromosome 5/6 complex (Smc5/6), and that a key function of HBx is to redirect the DNA-damage binding protein 1 (DDB1) E3 ubiquitin ligase to target this complex for degradation. By doing so, HBx alleviates transcriptional repression by Smc5/6 and stimulates HBV gene expression. In this review, we discuss in detail how the interplay between HBx and Smc5/6 was identified and characterized. We also discuss what is known regarding the repression of cccDNA transcription by Smc5/6, the timing of HBx expression, and the potential role of HBx in promoting hepatocellular carcinoma (HCC).\",\n \"title\": \"Identifying and Characterizing Interplay between Hepatitis B Virus X Protein and Smc5/6\"\n },\n {\n \"docid\": \"18882947\",\n \"text\": \"The HMG-box factor Tcf1 is required during T-cell development in the thymus and mediates the nuclear response to Wnt signals. Tcf1(-/-) mice have previously been characterized and show developmental blocks at the CD4-CD8- double negative (DN) to CD4+CD8+ double positive transition. Due to the blocks in T-cell development, Tcf1(-/-) mice normally have a very small thymus. Unexpectedly, a large proportion of Tcf1(-/-) mice spontaneously develop thymic lymphomas with 50% of mice developing a thymic lymphoma/leukemia at the age of 16 wk. These lymphomas are clonal, highly metastatic, and paradoxically show high Wnt signaling when crossed with Wnt reporter mice and have high expression of Wnt target genes Lef1 and Axin2. In wild-type thymocytes, Tcf1 is higher expressed than Lef1, with a predominance of Wnt inhibitory isoforms. Loss of Tcf1 as repressor of Lef1 leads to high Wnt activity and is the initiating event in lymphoma development, which is exacerbated by activating Notch1 mutations. Thus, Notch1 and loss of Tcf1 functionally act as collaborating oncogenic events. Tcf1 deficiency predisposes to the development of thymic lymphomas by ectopic up-regulation of Lef1 due to lack of Tcf1 repressive isoforms and frequently by cooperating activating mutations in Notch1. Tcf1 therefore functions as a T-cell-specific tumor suppressor gene, besides its established role as a Wnt responsive transcription factor. Thus, Tcf1 acts as a molecular switch between proliferative and repressive signals during T-lymphocyte development in the thymus.\",\n \"title\": \"The Nuclear Effector of Wnt-Signaling, Tcf1, Functions as a T-Cell–Specific Tumor Suppressor for Development of Lymphomas\"\n },\n {\n \"docid\": \"23356816\",\n \"text\": \"The mammalian A-type cyclin family consists of two members, cyclin A1 (encoded by Ccna1) and cyclin A2 (encoded by Ccna2). Cyclin A2 promotes both G1/S and G2/M transitions, and targeted deletion of Ccna2 in mouse is embryonic lethal. Cyclin A1 is expressed in mice exclusively in the germ cell lineage and is expressed in humans at highest levels in the testis and certain myeloid leukaemia cells. To investigate the role of cyclin A1 and possible redundancy among the cyclins in vivo, we generated mice bearing a null mutation of Ccna1. Ccna1-/- males were sterile due to a block of spermatogenesis before the first meiotic division, whereas females were normal. Meiosis arrest in Ccna1–/– males was associated with increased germ cell apoptosis, desynapsis abnormalities and reduction of Cdc2 kinase activation at the end of meiotic prophase. Cyclin A1 is therefore essential for spermatocyte passage into the first meiotic division in male mice, a function that cannot be complemented by the concurrently expressed B-type cyclins.\",\n \"title\": \"Cyclin A1 is required for meiosis in the male mouse\"\n },\n {\n \"docid\": \"8909176\",\n \"text\": \"Maltose metabolism of baker's yeast (Saccharomyces cerevisiae) in lean dough is negatively influenced by glucose repression, thereby delaying the dough fermentation. To improve maltose metabolism and leavening ability, it is necessary to alleviate glucose repression. The Snf1 protein kinase is well known to be essential for the response to glucose repression and required for transcription of glucose-repressed genes including the maltose-utilization genes (MAL). In this study, the SNF1 overexpression and deletion industrial baker's yeast strains were constructed and characterized in terms of maltose utilization, growth and fermentation characteristics, mRNA levels of MAL genes (MAL62 encoding the maltase and MAL61 encoding the maltose permease) and maltase and maltose permease activities. Our results suggest that overexpression of SNF1 was effective to glucose derepression for enhancing MAL expression levels and enzymes (maltase and maltose permease) activities. These enhancements could result in an 18% increase in maltose metabolism of industrial baker's yeast in LSMLD medium (the low sugar model liquid dough fermentation medium) containing glucose and maltose and a 15% increase in leavening ability in lean dough. These findings provide a valuable insight of breeding industrial baker's yeast for rapid fermentation.\",\n \"title\": \"Effects of SNF1 on Maltose Metabolism and Leavening Ability of Baker's Yeast in Lean Dough.\"\n },\n {\n \"docid\": \"8331432\",\n \"text\": \"The transcription factor HNF3 and linker histones H1 and H5 possess winged-helix DNA-binding domains, yet HNF3 and other fork head-related proteins activate genes during development whereas linker histones compact DNA in chromatin and repress gene expression. We compared how the two classes of factors interact with chromatin templates and found that HNF3 binds DNA at the side of nucleosome cores, similarly to what has been reported for linker histone. A nucleosome structural binding site for HNF3 is occupied at the albumin transcriptional enhancer in active and potentially active chromatin, but not in inactive chromatin in vivo. While wild-type HNF3 protein does not compact DNA extending from the nucleosome, as does linker histone, site-directed mutants of HNF3 can compact nucleosomal DNA if they contain basic amino acids at positions previously shown to be essential for nucleosomal DNA compaction by linker histones. The results illustrate how transcription factors can possess special nucleosome-binding activities that are not predicted from studies of factor interactions with free DNA.\",\n \"title\": \"Binding of the winged-helix transcription factor HNF3 to a linker histone site on the nucleosome.\"\n },\n {\n \"docid\": \"12652963\",\n \"text\": \"MicroRNAs (miRNAs) are ∼22 nt non-coding RNAs that typically bind to the 3' UTR of target mRNAs in the cytoplasm, resulting in mRNA destabilization and translational repression. Here, we report that miRNAs can also regulate gene expression by targeting non-coding antisense transcripts in human cells. Specifically, we show that miR-671 directs cleavage of a circular antisense transcript of the Cerebellar Degeneration-Related protein 1 (CDR1) locus in an Ago2-slicer-dependent manner. The resulting downregulation of circular antisense has a concomitant decrease in CDR1 mRNA levels, independently of heterochromatin formation. This study provides the first evidence for non-coding antisense transcripts as functional miRNA targets, and a novel regulatory mechanism involving a positive correlation between mRNA and antisense circular RNA levels.\",\n \"title\": \"miRNA-dependent gene silencing involving Ago2-mediated cleavage of a circular antisense RNA.\"\n },\n {\n \"docid\": \"37438296\",\n \"text\": \"Age-dependent decline in skeletal muscle function leads to several inherited and acquired muscular disorders in elderly individuals. The levels of microRNAs (miRNAs) could be altered during muscle maintenance and repair. We therefore performed a comprehensive investigation for miRNAs from five different periods of bovine skeletal muscle development using next-generation small RNA sequencing. In total, 511 miRNAs, including one putatively novel miRNA, were identified. Thirty-six miRNAs were differentially expressed between prenatal and postnatal stages of muscle development including several myomiRs (miR-1, miR-206 and let-7 families). Compared with miRNA expression between different muscle tissues, 14 miRNAs were up-regulated and 22 miRNAs were down-regulated in the muscle of postnatal stage. In addition, a novel miRNA was predicted and submitted to the miRBase database as bta-mir-10020. A dual luciferase reporter assay was used to demonstrate that bta-mir-10020 directly targeted the 3'-UTR of the bovine ANGPT1 gene. The overexpression of bta-mir-10020 significantly decreased the DsRed fluorescence in the wild-type expression cassette compared to the mutant type. Using three computational approaches - miranda, pita and rnahybrid - these differentially expressed miRNAs were also predicted to target 3609 bovine genes. Disease and biological function analyses and the KEGG pathway analysis revealed that these targets were statistically enriched in functionality for muscle growth and disease. Our miRNA expression analysis findings from different states of muscle development and aging significantly expand the repertoire of bovine miRNAs now shown to be expressed in muscle and could contribute to further studies on growth and developmental disorders in this tissue type.\",\n \"title\": \"Altered microRNA expression in bovine skeletal muscle with age.\"\n },\n {\n \"docid\": \"27949347\",\n \"text\": \"TP53 is the most frequently mutated gene in human cancer. Functionally, p53 is activated by a host of stress stimuli and, in turn, governs an exquisitely complex anti-proliferative transcriptional program that touches upon a bewildering array of biological responses. Despite the many unveiled facets of the p53 network, a clear appreciation of how and in what contexts p53 exerts its diverse effects remains unclear. How can we interpret p53's disparate activities and the consequences of its dysfunction to understand how cell type, mutation profile, and epigenetic cell state dictate outcomes, and how might we restore its tumor-suppressive activities in cancer?\",\n \"title\": \"Putting p53 in Context\"\n },\n {\n \"docid\": \"31882215\",\n \"text\": \"We describe robust induction of autophagy during the reprogramming of mouse fibroblasts to induced pluripotent stem cells by four reprogramming factors (Sox2, Oct4, Klf4 and c-Myc), henceforth 4F. This process occurs independently of p53 activation, and is mediated by the synergistic downregulation of mechanistic target of rapamycin complex 1 (mTORC1) and the induction of autophagy-related genes. The 4F coordinately repress mTORC1, but bifurcate in their regulation of autophagy-related genes, with Klf4 and c-Myc inducing them but Sox2 and Oct4 inhibiting them. On one hand, inhibition of mTORC1 facilitates reprogramming by promoting cell reshaping (mitochondrial remodelling and cell size reduction). On the other hand, mTORC1 paradoxically impairs reprogramming by triggering autophagy. Autophagy does not participate in cell reshaping in reprogramming but instead degrades p62, whose accumulation in autophagy-deficient cells facilitates reprogramming. Our results thus reveal a complex signalling network involving mTORC1 inhibition and autophagy induction in the early phase of reprogramming, whose delicate balance ultimately determines reprogramming efficiency.\",\n \"title\": \"Autophagy and mTORC1 regulate the stochastic phase of somatic cell reprogramming\"\n }\n]"}}},{"rowIdx":166,"cells":{"query_id":{"kind":"string","value":"4900"},"query":{"kind":"string","value":"How to calculate lump sum required to generate desired monthly income?"},"positive_passages":{"kind":"list like","value":[{"docid":"477062","text":"The product you seek is called a fixed immediate annuity. You also want to be clear it's inflation adjusted. In the US, the standard fixed annuity for a 40year old male (this is the lowest age I find on the site I use) has a 4.6% return. $6000/ yr means one would pay about $130,000 for this. The cost to include the inflation adder is about 50%, from what I recall. So close to $200,000. This is an insurance product, by the way, and you need to contact a local provider to get a better quote.","title":""}],"string":"[\n {\n \"docid\": \"477062\",\n \"text\": \"The product you seek is called a fixed immediate annuity. You also want to be clear it's inflation adjusted. In the US, the standard fixed annuity for a 40year old male (this is the lowest age I find on the site I use) has a 4.6% return. $6000/ yr means one would pay about $130,000 for this. The cost to include the inflation adder is about 50%, from what I recall. So close to $200,000. This is an insurance product, by the way, and you need to contact a local provider to get a better quote.\",\n \"title\": \"\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"254245","text":"What's the present value of using the payment plan? In all common sense the present value of a loan is the value that you can pay in the present to avoid taking a loan, which in this case is the lump sum payment of $2495. That rather supposes the question is a trick, providing irrelevant information about the stock market. However, if some strange interpretation is required which ignores the lump sum and wants to know how much you need in the present to pay the loan while being able to make 8% on the stock market that can be done. I will initially assume that since the lender's APR works out about 9.6% per month that the 8% from the stock market is also per month, but will also calculate for 8% annual effective and an 8% annual nominal rate. The calculation If you have $x in hand (present value) and it is exactly enough to take the loan while investing in the stock market, the value in successive months is $x plus the market return less the loan payment. In the third month the loan is paid down so the balance is zero. I.e. So the present value of using the payment plan while investing is $2569.37. You would need $2569.37 to cover the loan while investing, which is more than the $2495 lump sum payment requires. Therefore, it would be advisable to make the lump sum payment because it is less expensive: If you have $2569.37 in hand it would be best to pay the lump sum and invest the remaining $74.37 in the stock market. Otherwise you invest $2569.37 (initially), pay the loan and end up with $0 in three months. One might ask, what rate of return would the stock market need to yield to make it worth taking the loan? The APR proposed by the loan can be calculated. The present value of a loan is equal to the sum of the payments discounted to present value. I.e. with ∴ by induction So by comparing the $2495 lump sum payment with $997 over 3 x monthly instalments the interest rate implied by the loan can be found. Solving for r If you could obtain 9.64431% per month on the stock market the $x cash in hand required would be calculated by This is equal to the lump sum payment, so the calculated interest is comparable to the stock market rate of return. If you could gain more than 9.64431% per month on the stock market it would be better to invest and take the loan. Recurrence Form Solving the recurrence form shows the calculation is equivalent to the loan formula, e.g. becomes v[m + 1] = (1 + y) v[m] - p where v[0] = pv where In the final month v[final] = 0, i.e. when m = 3 Compare with the earlier loan formula: s = (d - d (1 + r)^-n) / r They are exactly equivalent, which is quite interesting, (because it wasn't immediately obvious to me that what the lender charges is the mirror opposite of what you gain by investing). The present value can be now be calculated using the formula. Still assuming the 8% stock market return is per month. If the stock market yield is 8% per annum effective rate and if it is given as a nominal annual yield, 8% compounded monthly","title":""},{"docid":"4734","text":"First let's define some terms. Your accrued benefit is a monthly benefit payable at your normal retirement age (usually 65). It is usually a life-only benefit but may have a number of years guaranteed or may have a survivor piece. It is defined by a plan formula (ie, it is a defined benefit). A lump sum is how much that accrued benefit is worth right now. Lump sums are based on applicable interest rates and mortality tables specified by the IRS (interest rates are released monthly, mortality annually). Your plan can either use the same interest rates for a whole year, or they can use new ones each month. Affecting your lump sum is whether your accrued benefit is payable now (immediately, you are age 65), or later (deferred, you are now age 30). For example, instead of being paid an annuity assume you are paid just one payment of $1,000 on your 65th birthday. The lump sum of that for a 65 year old would be $1,000 since there would be no interest discount, and no chance of dying before payment. For a 30 year old, at 4% interest the lump sum would be about $237 (including mortality discount). At age 36 the lump sum is $246. So the lump sum will get bigger just because you get older. Very important is the interest discount. At age 30 in the example, 2% interest would produce a $467 lump sum. And at 6% $122. The bigger the rate, the smaller the lump sum because interest helps an amount now grow bigger in the future. To complicate things, since 2008 the IRS bases lump sums on 3 different interest rates. The monthy annuity payments made within 5 years of the lump sum date use the 1st rate, past 5 and within 20 years use the 2nd rate, and past that use the 3rd rate. Since you are age 30, all of your monthly annuity payments would be made after 20 years, so that makes it simple since we'll only have to look at the 3rd rate. When you reach age 45 the 2nd rate will kick in. Here is the table of interest rates published by the IRS: http://www.irs.gov/Retirement-Plans/Minimum-Present-Value-Segment-Rates You'll find your rates above on the 2013 line for Aug-12. That means your lump sum is being made in 2013 and it is being based on the month August 2012. Most likely your plan will use the same rates for its entire plan year. But what is your plan year? If it is the calendar year, then you would have a 5 month lookback for the rates. But if is a September to August plan year with a 1 month lookback, the rates would have changed between August and September. Your August lump sum would be based on 4.52%, your September on would be based on 5.58% (see the All line for Aug-13). For comparison, a 30 year old with a $100 annuity payable at age 65 would have a lump sum value of $3,011 at 4.52%, but a lump sum value of $1,931 at 5.58%. The change in your accrued benefit by month will obviously have some impact on the lump sum value, but not as much as the change in interest rates if there is one. The amount they actually contribute to the plan has nothing to do with the value of the lump sum though.","title":""},{"docid":"188384","text":"\"I got $3394.83 The first problem with this is that it is backwards. The NPV (Net Present Value) of three future payments of $997 has to be less than the nominal value. The nominal value is simple: $2991. First step, convert the 8% annual return from the stock market to a monthly return. Everyone else assumed that the 8% is a monthly return, but that is clearly absurd. The correct way to do this would be to solve for m in But we often approximate this by dividing 8% by 12, which would be .67%. Either way, you divide each payment by the number of months of compounding. Sum those up using m equal to about .64% (I left the calculated value in memory and used that rather than the rounded value) and you get about $2952.92 which is smaller than $2991. Obviously $2952.92 is much larger than $2495 and you should not do this. If the three payments were $842.39 instead, then it would about break even. Note that this neglects risk. In a three month period, the stock market is as likely to fall short of an annualized 8% return as to beat it. This would make more sense if your alternative was to pay off some of your mortgage immediately and take the payments or yp pay a lump sum now and increase future mortgage payments. Then your return would be safer. Someone noted in a comment that we would normally base the NPV on the interest rate of the payments. That's for calculating the NPV to the one making the loan. Here, we want to calculate the NPV for the borrower. So the question is what the borrower would do with the money if making payments and not the lump sum. The question assumes that the borrower would invest in the stock market, which is a risky option and not normally advisable. I suggest a mortgage based alternative. If the borrower is going to stuff the money under the mattress until needed, then the answer is simple. The nominal value of $2991 is also the NPV, as mattresses don't pay interest. Similarly, many banks don't pay interest on checking these days. So for someone facing a real decision like this, I'd almost always recommend paying the lump sum and getting it over with. Even if the payments are \"\"same as cash\"\" with no premium charged.\"","title":""},{"docid":"407726","text":"\"An annuity is a product. In simple terms, you hand over a lump sum of cash and receive an agreed annual income until you die. The underlying investment required to reach that income level is not your concern, it's the provider's worry. So there is a huge mount of security to the retiree in having an annuity. It is worth pointing out that with simple annuities where one gives a lump sum of money to (typically) an insurance company, the annuity payments cease upon the death of the annuitant. If any part of the lump sum is still left, that money belongs to the company, not to the heirs of the deceased. Fancier versions of annuities cover the spouse of the annuitant as well (joint and survivor annuity) or guarantee a certain number of payments (e.g. 10-year certain) regardless of when the annuitant dies (payments for the remaining certain term go to the residual beneficiary) etc. How much of an annuity payment the company offers for a fixed lump sum of £X depends on what type of annuity is chosen; usually simple annuities give the maximum bang for the buck. Also, different companies may offer slightly different rates. So, why should one choose to buy an annuity instead of keeping the lump sum in a bank or in fixed deposits (CDs in US parlance), or invested in the stock market or the bond market, etc., and making periodic withdrawals from these assets at a \"\"safe rate of withdrawal\"\"? Safe rates of withdrawal are often touted as 4% per annum in the US, though there are newer studies saying that a smaller rate should be used. Well, safe rates of withdrawal are designed to ensure that the retiree does not use up all the money and is left destitute just when medical bills and other costs are likely to be peaking. Indeed, if all the money were kept in a sock at home (no growth at all), a 4% per annum withdrawal rate will last the retiree for 25 years. With some growth of the lump sum in an investment, somewhat larger withdrawals might be taken in good years, but that 4% is needed even when the investments have declined in value because of economic conditions beyond one's control. So, there are good things and bad things that can happen if one chooses to not buy an annuity. On the other hand, with an annuity, the payments will continue till death and so the retiree feels safer, as Chris mentioned. There is also the serenity in not having to worry how the investments are doing; that's the company's business. A down side, of course, is that the payments are fixed and if inflation is raging, the retiree still gets the same amount. If extra cash is needed one year for unavoidable expenses, the annuity will not provide it, whereas the lump sum (whether kept in a sock or invested) can be drawn on for the extra expense. Another down side is that any money remaining is gone, with nothing left for the heirs. On the plus side, the annuity payments are usually larger than those that the retiree will get via the safe rate of withdrawal method from the lump sum. This is because the insurance company is applying the laws of large numbers: many annuitants will not survive past their life expectancy, and their leftover monies are pure profit to the insurance company, often more than enough (when invested properly by the company) to pay those old codgers who continue to live past their life expectancy. Personally, I wouldn't want to buy an annuity with all my money, but getting an annuity with part of the money is worthwhile. Important: The annuity discussed in this answer is what is sometimes called a single-premium or an immediate annuity. It is purchased at the time of retirement with a single (large) lump sum payment. This is not the kind of annuity that is described in JAGAnalyst's answer which requires payment of (much smaller) premiums over many years. Search this forum for variable annuity to learn about these types of annuities.\"","title":""},{"docid":"487621","text":"So my advice for your financial situation depends on your aims. Are you aiming to: - Completely clear your debt - Clear one card to free up more monthly income. - Clear some debt to allow further controlled spending - Clear one card and focus on just using one, having 2nd as emergency. There are other things you may wish to do but you said to pay off some / all of 2 credit card bills. If you want to contact me I can plan this more precisely. Some seem the same but other factors can come into play as well. Differing rates of interest make the options clearer. My first advice would be to call the card companies and see if you can get better rates first. SCENARIO (some figures made up for visual) Credit Card Debts 8,000 8,000 Monthly payment 100 100 APR % 10 10 Ignoring APR this will be 80 months to repay (otherwise 140 months using my example amounts above) £28,000 repaid over 11 years 8 months. Your Suggestion As per your suggestion originally, paying off cards equally will allow smaller debt on both cards. Credit Card Debt 3,000 3,000 Monthly payment 100 100 APR % 10 10 With a 0% APR this would be paid off in 2 years 6 months. Cards are available to get free balance transfers, need to look into this. With the 10% APR this would take 3 years 1 month. £10,000 lump and £7,400 repaid over 3 years 1 month (saving £10,600 and 8 years 7 months) AIM: To clear debt completely. My advice here is to use the £10,000 lump sum to pay off one credit card, the remaining £2,000 can then come off the other card. This will free up your outgoings (was 2 x £100) by £100. But then use this £100 to pay off the card, this will result in the following: Credit Card Debt 6,000 Monthly payment 200 APR % 10 With a 0% APR this would be paid off in 2 years 6 months. Cards are available to get free balance transfers, need to look into this. With 10% APR this would take roughly 3 years 1 month. £10,000 lump and £7,400 repaid over 3 years 1 month (saving £10,600 and 8 years 7 months). This option is the same as above, but you have the options on the odd tight month to reduce payments to £100. This also will allow the 2nd card to be used interest free for an emergency purchase (to be paid off without any interest charge) If rates are different, pay of the one with the higher APR AIM: Clear one card to free up more monthly income. AIM: Clear one card and focus on just using one, having 2nd as emergency. Same as above, but don’t increase to £200, leave monthly payment at £100. Credit Card Debt 6,000 Monthly payment 100 APR % 10 With a 0% APR this would be paid off in 5 years. With the 10% APR this would take 88 months (7 years 4 months) £10,000 lump and £8,800 repaid over 7 years and 4 months (saving £9,200 and 4 years 4 months). This also allows for some extra spending (even racking back up the debt – although not advised) AIM: Clear some debt to allow further controlled spending As above apart from this will allow you to spend to get back up to full £16,000 debt. NOTE My figures are theoretical, paying off £500 (£250x2) a month instead of the £100 (10%APR) would take: Lump sum 10,000, remaining 6,000 – 14 months (£17,000 paid) Lump sum 5,000, remaining 2 x 5,500 – 26 months (£18,000 paid) Lump Sum 0, remaining 2 x 8,000 – 40 months (£20,000 paid) Now I have finished waffling, I hope you have an idea on what you are aiming to achieve and a better idea of what to do when you receive the income Stephen.","title":""},{"docid":"323238","text":"Have her pay something like a friendly monthly rent. This should be less than half of the monthly mortgage cost, since you are assuming the risk (and benefits) of a mortgage and closer to the rent of similar places near you. For when you get married and she is to have half the apartment, have a pre-agreed way to calculate a lump-sum that she needs to provide to match your own contributions up to that time, as if you two had equal contributions from the beginning. The financially precise way to do it would be to have her pay more than the mere sum of the amount (since she will be providing the amount at a later time than you), but I would be generous and skip this in your place if the difference is not too big. If you break up, she will have payed what would be a fair amount of rent, as if you two were renting, so, in this sense, it is fair that she would not have a claim on the apartment. In case that you two would like that she keeps the apartment, you can just sell it to her, having her pay this same amount as above and assume responsibility for the rest of the mortgage.","title":""},{"docid":"432280","text":"\"This is a bit pornographic, isn't it, in that we're looking at something we'd like to do (namely, \"\"win the big lottery!\"\") but probably won't ever have this happen to us. :) Anyway. Ignoring the fact that this is kind of a hypothetical question... Gotta go with The Straight Dope on this one, when deciding whether to take an annuity or a lump sum: What assumed interest rate is underlying the calculations? Do you think you can earn significantly more than that rate on your own? If so, take the lump sum cash value. If not, go with the annuity. What are your financial needs, both immediate and over the next twenty years? Do you need a steady flow of income? If you take the lump sum and invest it poorly or lose it, how much will it hurt you? If you give up your job to enjoy your wealth, what will happen if you're still alive when the annuity payments stop? You don't want to blow it all in a spree and then find yourself in poverty in your old age. What happens if you die before the annuity has been fully paid? As noted, there's the question of whether to ask in advance for an annuity - the tax treatment alone could overwhelm any other considerations.\"","title":""},{"docid":"8601","text":"Setting aside for the moment the very relevant issue of whether you need the full amount quickly, I'll just tackle comparing which option gives you to maximum amount of money (in terms of real dollars). The trick is, unless you think inflation will suddenly reverse itself or stop entirely (not likely), $50K today is worth a LOT more than $50K in 20 years. If you don't believe me, consider that just 30 years ago the average price for a mid-level new car was around $3k. When you grandfather says he got a burger for a nickel, he isn't talking about 2010 dollars. So, how do you account for this? Well, the way financial people and project managers do it to estimate how much to pay today for $1 at some point in the future is through a net present value (NPV) calculation. You can find a calculator here. In your question, you gave some numbers for the payout, but not the lump sum prize amount. Going solely on what you have provided, I calculate that you should take the lump sum if it is greater than $766,189.96 which is the net present value of 20 years of $50K Payments assuming 3% annual inflation, which is fairly a fairly reasonable number given history. However, if you think the out-of-control Gov't spending is going to send inflation through the roof (possible, but not a given), then you almost certainly would want the lump sum. I suppose in that scenario you might want the lump sum anyway because if the Govt starts filching on their obligations, doing it to a small number of lottery winners might be politically more popular than cutting other programs that affect a large number of voters.","title":""},{"docid":"559745","text":"\"@fredsbend, Hope this helps! \"\"I understand that a reverse mortgage can be paid out in two ways: A lump sum and monthly payments. I figure that if you take the lump sum, eventually, the bank wants you to start paying it back.\"\" Answer: Actually, there are 3 payout options, or 4 if you consider a combination payout as another one. There's a lump sum, a line of credit, or the monthly payout, or a combination. \"\"I figure that if you take the monthly payments, eventually, the bank stops paying out and wants you to pay it back. In both situations, interest accrues and this is how the bank makes money off of the deal\"\". Answer: The only time the monthly payments would stop would be if the borrower defaults on the lenders' terms or they no longer live at home. You are right though, and interest does accrue on whichever payment is decided on. I'm not sure how the lender makes money, probably by the interest, but I know borrowers are protected against high rates and owing more than your house. Here's an article I found that goes over the protections more in detail: https://www.americanadvisorsgroup.com/news/6-consumer-protections-reverse-mortgage-loan-borrowers. \"\"But what determines when you have to begin paying back the reverse mortgage? Some sources online seem to say that it's based only on if you die or would like to sell/move. That can't be right in all situations, because you could end up with a massive debt on a property more than its value.\"\" Answer: There are a lot of protections or regulations in place to protect anyone who takes out a reverse mortgage. One being, you can't owe MORE than your house is valued at during the time of repayment, a reverse mortgage is a non-recourse loan. In the instance that your house is less than you owe, you either sell the home and the proceeds are used to pay the loan and you keep the rest OR if you owe more than the house proceeds of the home go to the lender. Either way, you're not left paying for a \"\"mortgage\"\" without the house. In the case the parent, grandparent passes, then the heirs would have a choice of either paying back the reverse mortgage in payments, OR they can sell the house, heirs are protected during this as well to make sure they're not left with major debt in case of anything. Is there a formula to figure out when the bank stops the monthly payments and then wants it back? **Answer:**The amount becomes due if loan terms are not met, but the lender will discuss the options if it comes to that. Is there a different formula for when the lump sum would have to be paid back?\"\" Answer: Each payout option has the same terms and the same pay back terms. As long as terms are met, the lender can't ask for early repayment.\"","title":""},{"docid":"391583","text":"Retirement calculation, in general, should be based on the amount of money needed per year/month and the expected life expectancy. Life expectancy, if calculated to 90 years (let's say) indicates that post retirement age (60 yrs.) your accumulated/invested money should generate adequate income to cover your expenses till 90 years. The problem in general is not how long you shall live but what would be your expected spending from retirement to end of life expectancy. The idea is at the minimum your investments should generate income that is inflation adjusted. One way to do this is to consider your monthly expense now i.e. the expense that is absolute minimum for carrying on (food, electricity, water, medicines, household consumables, car petrol, insurance, servicing, entertainment, newspaper etc.) this does not contain the amortizable liabilities (home loan, child's education, other debts). It is better to take this amount per family rather than per person and yearly rather than monthly (as we tend to miss a lot of yearly expenses). This amount that you need today will increase at a Compounded Annual Growth Rate (CAGR) of the average inflation. For example, if today you spend 100 per year in 7 years you will need to spend appx. 200 at 10% inflation. Now, your investments will not increase post your retirement, so your current investment needs to do two things (1) give you your yearly requirement (2) grow by a fixed amount so that next year it can give you CAGR adjusted returns. In general, this kind of investment grows by high net amounts initially and slowly the growth decrease. The above can be calculated by Net Present value (NPV) formulae (http://en.wikipedia.org/wiki/Net_present_value). The key is to remember that the money that is invested when you retire should be able to give you inflation adjusted returns to cover your yearly expenses. How much money you need depends on your life style/expectation and how much return is received depends on the instruments that you invest on. As for your question above on the difference between the age of you and your spouse, it better to go with the consolidated family requirement and get an idea of how much investment is necessary and provision the same as soon as possible from your as well as your spouse's income. Hope this helps.- thanks","title":""},{"docid":"180071","text":"\"There are two options (according to Wells Fargo). You can either apply for a Business/Commercial Equity Loan or a Line of Credit. A loan is what it sounds like - they give you a lump sum of money for you to use and you have to pay it in monthly installments. A line of credit is like a credit card, you have money that you can borrow (up to a certain amount) and you have to make monthly payments. The process can differ for different business, they probably look at what your real estate is worth, how much money you are generating from it, etc. I am not recommending or endorsing Wells Fargo, other major banks offer the same types of products, Wells Fargo just happened to appear first when I searched for \"\"business line of credit\"\".\"","title":""},{"docid":"539112","text":"\"The specific \"\"State Pension\"\" plan you have linked to is provided by the government of the U.K. to workers resident there. More generally speaking, many countries provide some kind of basic worker's pension (or \"\"social security\"\") to residents. In the United States, it is called (surprise!) \"\"Social Security\"\", and in Canada most of us call ours \"\"Canada Pension Plan\"\". Such pensions are typically funded by payroll deductions distinct & separate from income tax deducted at source. You can learn about the variety of social security programs around the world courtesy of the U.S. Social Security Administration's own survey. What those and many other government or state pensions have in common, and the term or concept that I think you are looking for, is that they are typically defined benefit type of plans. A defined benefit or DB plan is where there is a promised (or \"\"defined\"\") benefit, i.e. a set lump sum amount (such as with a \"\"cash balance\"\" type of DB plan) or income per year in retirement (more typical). (Note: Defined benefit plans are not restricted to be offered by governments only. Many companies also offer DB plans to their employees, but DB plans in the private sector are becoming more rare due to the funding risk inherent in making such a long-term promise to employees.) Whereas a defined contribution or DC plan is one where employee and/or employer put money into a retirement account, the balance of which is invested in a selection of funds. Then, at retirement the resulting lump sum amount or annual income amounts (if the resulting balance is annuitized) are based on the performance of the investments selected. That is, with a DC plan, there is no promise of you getting either a set lump sum amount or a set amount of annual income at retirement! The promise was up front, on how much money they would contribute. So, the contributions are defined (often according to a matching contribution scheme), yet the resulting benefit itself is not defined (i.e. promised.) Summary: DB plans promise you the money (the benefit) you'll get at retirement. DC plans only promise you the money (the contributions) you get now.\"","title":""},{"docid":"217222","text":"The equation is the same one used for mortgage amortization. You first want to calculate the PV (present value) for a stream of $50K payments over 20 years at a10% rate. Then that value is the FV (future value) that you want to save for, and you are looking to solve the payment stream needed to create that future value. Good luck achieving the 10% return, and in knowing your mortality down to the exact year. Unless this is a homework assignment, which need not reflect real life. Edit - as indicated above, the first step is to get that value in 20 years: The image is the user-friendly entry screen for the PV calculation. It walks you though the need to enter rate as per period, therefore I enter .1/12 as the rate. The payment you desire is $50K/yr, and since it's a payment, it's a negative number. The equation in excel that results is: =PV(0.1/12,240,-50000/12,0) and the sum calculated is $431,769 Next you wish to know the payments to make to arrive at this number: In this case, you start at zero PV with a known FV calculated above, and known rate. This solves for the payment needed to get this number, $568.59 The excel equation is: =PMT(0.1/12,240,0,431769) Most people have access to excel or a public domain spreadsheet application (e.g. Openoffice). If you are often needing to perform such calculations, a business finance calculator is recommended. TI used to make a model BA-35 finance calculator, no longer in production, still on eBay, used. One more update- these equations whether in excel or a calculator are geared toward per period interest, i.e. when you state 10%, they assume a monthly 10/12%. With that said, you required a 20 year deposit period and 20 year withdrawal period. We know you wish to take out $4166.67 per month. The equation to calculate deposit required becomes - 4166.67/(1.00833333)^240= 568.59 HA! Exact same answer, far less work. To be clear, this works only because you required 240 deposits to produce 240 withdrawals in the future.","title":""},{"docid":"17633","text":"There can be Federal estate tax as well as State estate tax due on an estate, but it is not of direct concern to you. Estate taxes are paid by the estate of the decedent, not by the beneficiaries, and so you do not owe any estate tax. As a matter of fact, most estates in the US do not pay Federal estate tax at all because only the amount that exceeds the Federal exemption ($5.5M) is taxable, and most estates are smaller. State estate taxes might be a different matter because while many states exempt exactly what the Federal Government does, others exempt different (usually smaller) amounts. But in any case, estate taxes are not of concern to you except insofar as what you inherit is reduced because the estate had to pay estate tax before distributing the inheritances. As JoeTaxpayer's answer says more succinctly, what you inherit is net of estate tax, if any. What you receive as an inheritance is not taxable income to you either. If you receive stock shares or other property, your basis is the value of the property when you inherit it. Thus, if you sell at a later time, you will have to pay taxes only on the increase in the value of the property from the time you inherit it. The increase in value from the time the decedent acquired the property till the date of death is not taxable income to you. Exceptions to all these favorable rules to you is the treatment of Traditional IRAs, 401ks, pension plans etc that you inherit that contain money on which the decedent never paid income tax. Distributions from such inherited accounts are (mostly) taxable income to you; any part of post-tax money such as nondeductible contributions to Traditional IRAs that is included in the distribution is tax-free. Annuities present another source of complications. For annuities within IRAs, even the IRS throws up its hands at explaining things to mere mortals who are foolhardy enough to delve into Pub 950, saying in effect, talk to your tax advisor. For other annuities, questions arise such as is this a tax-deferred annuity and whether it was purchased with pre-tax money or with post-tax money, etc. One thing that you should check out is whether it is beneficial to take a lump sum distribution or just collect the money as it is distributed in monthly, quarterly, semi-annual, or annual payments. Annuities in particular have heavy surrender charges if they are terminated early and the money taken as a lump sum instead of over time as the insurance company issuing the annuity had planned on happening. So, taking a lump sum would mean more income tax immediately due not just on the lump sum but because the increase in AGI might reduce deductions for medical expenses as well as reduce the overall amount of itemized deductions that can be claimed, increase taxability of social security benefits, etc. You say that you have these angles sussed out, and so I will merely re-iterate Beware the surrender charges.","title":""},{"docid":"197576","text":"First of all depending on the type of IRA you may not have to pay taxes on withdrawals in the US at all. If you are withdrawing your principle from a Roth IRA then you don't owe taxes. Only when you withdraw the gains do you pay taxes on it. You have two options for withdrawals: Lump Sum Withdrawal: If you take a lump sum withdrawal you will owe taxes to the US (30% for non-resident aliens of the US), and according to DTAA; Article 23, you will file your taxes with India declaring your IRA or 401(k) withdrawal proceeds and claim credit on the taxes you paid to the US. Monthly Pension Withdrawal: You can also receive monthly pension payments and you will only be taxed in the country in which you are a resident of. This is according to DTAA, Article 20. You would then have to submit necessary documentation to your payer in the US so that they do not withhold any taxes in the US. Just as a side note it might be just better to keep the money where it is and let it grow or roll it over to a Roth IRA if you are currently in a lower tax bracket for maximum savings of your principle. Here is a link with more detailed information of what I provided you: http://articles.economictimes.indiatimes.com/2012-01-25/news/30663129_1_taxable-income-nri-401k-plan","title":""},{"docid":"465283","text":"After some thought, I follow Dave Ramsey's advice because it's simple and I can do the math in my head - no online calculator needed. :) You need Life Insurance if someone depends on your income. You can replace your income with a single lump sum of 8-10 times your current income where those who need your income, can get roughly your salary each year from the life insurance proceeds.","title":""},{"docid":"34538","text":"\"Some details in case you are interested: Being a defined benefit kind of pension plan, the formula for your Social Security benefits isn't tied directly to FICA contributions, and I'm not aware of any calculator that performs an ROI based on FICA contributions. Rather, how much you'll get in retirement is based on your average indexed monthly earnings. Here's some information on the Social Security calculation from the Social Security Administration - Primary Insurance Amount (PIA): For an individual who first becomes eligible for old-age insurance benefits or disability insurance benefits in 2013, or who dies in 2013 before becoming eligible for benefits, his/her PIA will be the sum of: (a) 90 percent of the first $791 of his/her average indexed monthly earnings, plus (b) 32 percent of his/her average indexed monthly earnings over $791 and through $4,768, plus (c) 15 percent of his/her average indexed monthly earnings over $4,768. Here's an example. Of course, to calculate a benefit in the future, you'll need to calculate projected average indexed monthly earnings; more details here. You'll also need to make assumptions about what those bend points might be in the future. The average wage indexing values for calculating the AIME are available from the Social Security Administration's site, but future indexing values will also need to be projected based on an assumption about their inflation. You'll also need to project the Contribution and Benefit Base which limits the earnings used to calculate contributions and benefits. Also, the PIA calculation assumes benefits are taken at the normal retirement age. Calculating an early or late retirement factor is required to adjust benefits for another age. Then, whatever benefits you get will increase each year, because the benefit is increased based on annual changes in the cost of living. Performing the series of calculations by hand isn't my idea of fun, but implementing it as a spreadsheet (or a web page) and adding in some \"\"ROI based on FICA contributions\"\" calculations might be an interesting exercise if you are so inclined? For completeness sake, I'll mention that the SSA also provides source code for a Social Security Benefit Calculator.\"","title":""},{"docid":"320362","text":"\"You'd need to talk with an attorney familiar with Social Security, or an appropriately qualified SSA representative to be sure - but all signs point to the idea that unfortunately Social Security does not work the way your father was told it would. And if he doesn't file to receive benefits the reality is actually much worse than \"\"throwing away free money\"\"! However, this is not due to a complete misunderstanding of the system! Social Security does work the way he thinks in some instances, just that the rules don't apply to his exact situation! First of all, retroactive benefits come in a few forms: File and suspend to get a lump only if you really need it - BEFORE the age of 70 only! In this method you apply for retirement, but you tell the SSA to suspend/delay your benefits. You are entitled to full lump sum of the payments you deferred...but at a cost of getting lower monthly benefits permanently (and that also lowers spousal and dependent children's benefits, too - if those could apply to your dad). But note that at the age of 70, Social Security will stop deferring the payments and start paying you the full maximum retirement benefit monthly, with no lump sum. This is a kind of emergency insurance policy for those who want to try to defer retirement benefits, but who want the opportunity to cash out and get the money they would have been getting \"\"just in case\"\". You can get up to 6 months of retroactive benefits, such as if you wait past your exact retirement age to apply for benefits. But no more: \"\"we cannot pay retroactive benefits for any month before you reached full retirement age or more than 6 months in the past\"\". As for after-death benefits, an estate can only get benefits that were already due to be paid, which generally means a person died and did not get their benefits for that month, so SSA can re-issue a check to the estate following these rules. But as a person cannot be due a lump sum payment after age 70 (for more than 6 months at most), the estate will only be able to get at most 1-6 months of payments (and 6 months is doubtful - you'll need to ask a lawyer if that much would even be possible). If your father was below 70 and wanted to file-and-suspend, the question of lump on death would be more complex and I don't know that answer - but once you are past 70 this doesn't matter any more as you aren't due a lump anymore. Given the above, we've established pretty clearly that if you don't claim your benefits within 6 months after age 70, any months of payment you would have gotten are just forfeited to the system. But if you claim the benefits and stick them in the bank, can they be taken? Well, if a lawsuit is really a worry, then yes these accumulated funds can required to pay a debt - but this potential for loss can be protected against without forfeiting the benefits entirely! This is not very common, but if your father doesn't need the money now he may be able to deposit some of the money into a special partially-lawsuit protected format of the Roth IRA (which has no age limits) as detailed here. If he never gets sued, that's OK - it's still his money! If he passes away, the value goes to his estate and does not disappear. And he doesn't forfeit any of his earned retirement benefits. Finally, I would like to share one last thing with you and your father. These benefits aren't free - he has been paying a portion of his paycheck for decades into Social Security, and now he is eligible for the maximum amount of benefits per month that he will qualify for - and if he wants to keep working he loses no benefit and the amount could potentially even go up. That's up to him. But not filing for benefits now will mean that all this money he's been paying in for decades will just be lost - they'll basically just be a tax he's paid out to other retirees. His estate (which means you kids) won't get any of it, either. That'd just be a waste for everyone involved. If you have continued doubts or questions, I wouldn't hesitate to consult a specialist lawyer or talk with the SSA directly to make sure this is all correct. It's his money, and he has earned his benefits for many years. I very much hope he gets to enjoy as much of them as he can!\"","title":""},{"docid":"308010","text":"As mentioned in other answers the interest you make is negligible and the calculations would depend on the bank. In saying that the general trend is calculate daily, pay monthly. A typical scenario would be that every night at midnight the interest for your account at that point in time is calculated. This occurs every midnight and at the end of the month the sum of those calculations will be added to your account. You could have had several significant transactions pass through your account in one day although if the interest is calculated at a specific point in time some transactions may not contribute to any interest. These calculations are worth thinking about, even in circumstances of negligible returns, as it could assist when considering combining credit cards with home loan offset accounts so it is not a complete waste of time to understand how interest is calculated. The more you know ;)","title":""},{"docid":"181732","text":"\"You can use the 6900 to make an investment. Or to buy something. That's why people keep reminding you that you could make interest. Because most people think of either 7200 now or paying the same 7200 over time. So you could just be storing the 7200 under the mattress until you pay it out. Obviously in that case, inflation doesn't matter (\"\"is not applicable\"\"). You've given up the use of the 7200 from the beginning. Think of it instead as 7200 now and twenty-three payments of 300 each. So 14,100 total. Then you can spend 6900 on something else at the beginning or spend 300 a month on other things. The difference between spending 6900 now and 300 in each of twenty-three months would be measured in inflation. Of course, this requires you to have both 7200 now and an income stream producing at least 300 a month. Another way of doing things is to take 6900 and invest it. Each month you remove 300 and use it to make a payment. We're now back to just one 7200, plus the interest over time. I would argue that this is still an inflation advantage. It's just that instead of spending the money, you invested it. And that of course is your prerogative. The point being that you would not have that opportunity if you paid up front. Now to calculate the difference in monthly payments of 300 euro using the above webpage what should I do? As already said, you would have to calculate twenty-three values and then sum them with the 300 you pay up front in the monthly. There are other ways to calculate it, if you are not using that particular tool. For example, there are formulas to calculate the net present value of an annuity. E.g. see Investopedia. Where: P = the present value of an annuity stream PMT = the dollar amount of each annuity payment r = the inflation rate n = the number of periods in which payments will be made Investopedia talks about interest rates, but you can put inflation there for this purpose. In that case, r might better be called the \"\"discount rate\"\". PMT is 300. r is whatever estimate you are using for inflation. E.g. .003 per period. n is 23. Note that the monthly inflation rate is smaller than the annual rate. So .003 is about 3.66% annually. 3.04% annually is more like .0025 a month. I found calculators for this with search terms \"\"present value of annuity calculator\"\". Some of the calculators will take the annual rate (3.66%) and number of periods per year as input. Or the calculator may take a monthly rate as a percentage (.3%) rather than as a decimal (.003). So be careful of the inputs. This gives me a net present value (NPV) of 6,657.69 for the 23 payments of 300, assuming .3%. Or 6957.69 is the NPV of the monthly payments and 7200 is the NPV of the 7200 up front. Obviously if you can pay less than 6957.69 up front rather than 7200, then it makes more sense to pay up front. Even without a discount though, it still may make more sense to pay up front. How much those intangibles are worth is up to you.\"","title":""},{"docid":"131451","text":"\"For example, for my employer I received a signing bonus, and a \"\"relocation lump sum\"\" separate from that signing bonus. The relocation lump sum is taxed and will appear as income on my W-2, and I can spend it on anything I want. That said, should the relocation lump sum count towards the entry quoted above in Form 3903, or would it be considered the same as any other bonus; thus allowing me to take a full deduction for all of my deductible travel expenses? The signing bonus and relocation lump sum will appear as regular income on your W-2. You can think of the relocation bonus as something to cover the pain and suffering the cost of moving, without needing to send in receipts. Lets assume that you meet the distance and time tests, so there is potential to save money on your taxes. Lets also put your actual moving expenses as $2500. If you have valid moving expenses the IRS will allow you to use them to reduce your AGI. So now you can reduce your AGI by the $2500. Enter the total amount your employer paid you for the expenses listed on lines 1 and 2 that is not included in box 1 of your Form W-2 (wages). This amount should be shown in box 12 of your Form W-2 with code P. My question is: what exact payments from your employer should be entered here? I realize that you can just write the number you get in box 12 with code P on your W-2, but I'm curious how they come up with this number. In some cases the company will reimburse you your moving expenses up to a maximum of $x. For example a maximum of $1000 That means you submit receipts for those expenses and they give you a check or add it to your next paycheck. The check will either be for the amount on your receipts or the maximum amount, whichever is smaller. In this situation with actual expenses of $2500 and a reimbursement of $1000 you can reduce your AGI by $1500.\"","title":""},{"docid":"270022","text":"As I see it the two main considerations are: Total amount of money received, for which the key variable is life expectancy. 41000 * 0.8 = 32800, so at £86 / week she would only be better off with the lump sum if she expected to live for less than ~7.3 years. Obviously none of us have a crystal ball, but you could make some assessment based on her current health, risk factors etc. to see whether that seemed feasible. Also you do have to bear in mind that the value of £86 in 7 years' time will be less than it is now - but I guess the £86 would be inflation adjusted? Her need for income (versus capital). If she takes a lump sum and invests it in a house, that is great but doesn't provide any income at all. If she has sufficient income from other sources (and forecasts this other income to continue until her death) then the lump sum might be more attractive, but if not then she would need to be sure that she wasn't tying up the money unnecessarily. Another option here would be using the lump sum to buy an annuity, and it might be wroth exploring this, but I doubt whether the rates would be good enough to beat the £86 / week she is being offered as an alternative. Another (lesser?) consideration is her future entitlement to state-funded care if needed in her later years. If you have assets above a certain amount you are expected to fund your own care, in which case having an expensive house might actually be more of a liability than a help.","title":""},{"docid":"30935","text":"\"No, I do not. The advice is to take advice :-) but it is not required. Several \"\"low cost\"\" SIPPs allow an \"\"Execution Only\"\" transfer from some pensions (generally not occupational or defined benefits schemes [where transfers are generally a bad idea anyway] but FAVCs such as mine are ok). Best Invest is one such, and the fees are indeed relatively low. As far as anyone knows, the government's plans for changes to rules on using pension funds would still apply even once I've transferred my pension pot and begun to withdraw funds (provided I don't commit myself to an annuity or other irrevocable investment). I am not a financial adviser, nor employed or otherwise connected with Best Invest, and I'm not endorsing their SIPP schemes, just giving them as an example of what can be done. [Added after I carried out my plan] I found the process very straightforward; I needed to apply for a pension fund with my new provider and fill in a transfer form, which set up the scheme and transferred the funds with no expense required. Once the money arrived in my pension account I filled in another form to take the lump sum and set up regular withdrawals from the fund. I had my lump sum within a couple of months of initiating the transfer. I'm very happy I did not take independent advice because it would have been very poor value for money. During my researches I was approached eagerly by one firm promising to get me my money quick and claiming to be an independent financial advisor. Luckily I mistrusted the service they offered.\"","title":""},{"docid":"173213","text":"\"Looking at some large lotto games out there, it seems that the lump sum (cash) option comes in at anywhere from about 50 to 70 percent of the jackpot amount (sum of annual payouts, typically over 20 to 30 years). I'm a fan of the phrase \"\"money today is better than money tomorrow.\"\" There's no telling how laws will change, taxes will change, if inflation will skyrocket, if you'll die early, if you or a family member will encounter a life-changing event, etc. By taking the lump sum option you trade a percentage of the winnings for the risk of the future unknowns. How much are those unknowns worth to you? The tax implications are something else to consider. In your example of a \"\"small\"\" jackpot with $50,000 annual payouts, it's likely that you could still avoid the highest tax bracket each year, whereas taking the lump sum would be taxed at the highest rate (35% of the amount above $373k, for a single filer in 2010). However, this might not make much of a difference for large jackpots with higher annual payouts. With the lump sum option, you also have a greater potential of investment returns (and losses) since you can put all the money to work for you right away. It also allows you to purchase larger assets sooner, if that's something that interests you. In the end, I'd say the reduced risk and the higher return potential of the lump sum option is well worth the reduced payout. I'd also suggest not playing the lottery :)\"","title":""},{"docid":"488638","text":"\"Really this is no different from any kind of large lump sum and having a mortgage. There are probably many questions and answers on this subject. It really doesn't matter that the proceeds were the result of a sale, an inheritance would not change the answer. I think it is important to note that the proceeds will not eliminate the house 2 mortgage. A high level choice of investment one makes is between equity (such as stock) and debt investments (such as bonds and mortgages). You are in a unique case of being able to invest in your own mortgage with no investment fee. This may tip the scales in favor of paying down the mortgage. It is difficult to answer in your specific case as we don't know the rest of your finances. Do you have a sizable 401K that is heavily invested in stocks? Do you have the need for a college fund? Do you have an emergency fund? Do you have a desire to own several homes generating income property? If it was me I'd do the following in order, skipping steps I may have already completed: I've heard that the bank may agree to a \"\"one time adjustment\"\" to lower the payments on Mortgage #2 because of paying a very large payment. Is this something that really happens? I really kind of hate this attitude. Your goal is to get rid of the mortgage in a timely manner. Doing such makes paying for kids college a snap, reduces the income one might need in retirement, basically eliminates the need for life insurance, and gives one a whole lot of money to have fun with.\"","title":""},{"docid":"497281","text":"There are a number of scholarly articles on the subject including a number at the end of the Vanguard article you reference. However, unfortunately like much of financial research you can't look at the articles without paying quite a bit. It is not easy to make a generic comparison between lump-sum and dollar cost averaging because there are many ways to do dollar cost averaging. How long do you average over? Do you evenly average or exponentially put the money to work? The easiest way to think about this problem though is does the extra compounding from investing more of the money immediately outweigh the chance that you may have invested all the money when the market is overvalued. Since the market is usually near the correct value investing in lump sum will usually win out as the Vanguard article suggests. As a side note, while using DCA on a large one time sum of money is generally not optimal, if you have a consistent salary DCA by frequently investing a portion of your salary has been frequently shown to be a very good idea of long periods over saving up a bunch of money and investing it all at once. In this case you get the compounding advantage of investing early and you avoid investing a large chunk of money when the market is overvalued.","title":""},{"docid":"68872","text":"\"Note - this is a complicated topic. I've read the rules multiple times and I'm still not sure I understand them perfectly. So please take this with a pinch of salt and read the rules for yourself. The time(s) at which a test is done against the LTA are known as a \"\"Benefit Crystallization Event\"\" (BCE). There are 13 of these (!) - they're numbered 1-9 with the addition of some extras numbered 5A-D. However, the most important ones for those with defined contribution pensions are: Broadly, the idea is that a BCE occurs when you start taking money out of your pension, and when you reach age 75. Each time one happens, the amount you are taking out (\"\"crystallizing\"\") gets compared against the LTA and a certain percentage of your LTA gets designated as being used. Crystallising doesn't necessarily mean you actually receive the money immediately, just that some of your money is switched into a mode where you can start receiving it in different ways. The rules are designed to avoid double counting, so broadly anything that was taken off your LTA won't be taken off a second time. The cumulative use of your LTA is tracked as a percentage rather than an absolute amount, to take account of any changes in the LTA between the different times you crystallise money. For example if you crystallise £100K when the LTA is £1mn, that's 10% of your LTA gone. If later on the LTA has risen to £1.1mn and you take out £110K, that's another 10%. Once you hit 100%, you start paying a LTA charge on any excess. The really simple path here is if you just get an annuity with your entire pot, before hitting age 75 (and you don't make any further pension contributions after). Then only BCE 4 applies: your pension pot, all of which is being used to buy the annuity, is compared with the LTA. After this point your entire pension pot is considered to be crystallized, so no more BCEs will apply - the tests at age 75 only apply if you still have money that you haven't taken out or used to buy an annuity. The annuity payments themselves will be subject to income tax at your normal rate at the time you receive them, i.e. 0%, 20%, 40% or 45% depending on how much other income you have. In reality most people would want to take 25% of their pot as a lump sum at the same time as buying an annuity, given that it's tax-free if you're under the LTA. At this point BCE 6 applies in addition to BCE 4, but again the overall effect of the test is pretty simple, look at the total pension pot (lump sum + cost of annuity), and if it's under the LTA you're fine. Again, at this point no more BCEs will apply as all the money is considered to have been fully distributed. If you only use part of the money for an annuity/lump sum, then only that part of the money is compared against the LTA, and the rest stays in your pension and will be compared later. The 25% limit for a tax-free lump sum applies to the total you are taking out at that point: if you have £200K and are taking out £100K, you can take out £25K as a tax-free lump sum and use £75K for the annuity. The other £100K stays in your pension. Many people see annuity rates as very low and will want to take on more risk (and reward) by using \"\"Drawdown\"\" for at least part of their pension. Essentially, you can designate part of your pension for drawdown, and at that point BCE 1 applies to the money you designate. Once designated, you can start drawing the money out as income, which will be taxed at your normal income tax rate at the time you receive it. Again, you can take 25% as a lump sum at this point which will be subject to BCE 6. There's also an alternative route where you put everything into \"\"flexi-access drawdown\"\" without taking any lump sum immediately, and then as you actually withdraw income, 25% is tax-free and the rest is taxed as income. The overall effect is the same, but it gives you more control over when you get the tax-free bit. However, because with drawdown you can actually leave the money in your pension and growing tax-free, there's a further test against the LTA at age 75 under BCE 5A. To avoid double-counting (\"\"prevention of overlap\"\"), the amount left in the drawdown fund at that point is reduced by whatever was previously tested against BCE 1. So if you put £150K into drawdown initially, and it's grown to £200K by age 75, then another £50K will crystallise under BCE 5A. I think that if you put £150K into drawdown initially and it grows by £50K, but you take that out as income so that only £150K (or less) remains at age 75, then the amount crystallising under BCE 5A is nil. Also, when money is in drawdown, you can choose to use it to buy an annuity. BCE 4 is applied at this point (if before age 75), but as with BCE 5A, this is reduced by anything that was previously crystallised under BCE 1. If you only use some of it to buy an annuity, the reduction is pro-rataed, e.g. if you started out with £150K moved into drawdown, and later it has grown to £200K and you use £100K to buy an annuity, then the reduction is £75K so £25K is considered to have crystallised under BCE 4. Once you reach age 75, as well as any money that's still in drawdown, anything you haven't yet crystallised at all gets tested against the LTA under BCE 5B. Broadly, once you go over the LTA, the charges are simple: There's never any explanation given for these two rates, but I think it's all based on trying to at least cancel out the benefit you got from using your pension, on the assumption that: So with the 25% charge + 20% income tax, if you take out £100, you'll end up with £75 gross income, so £60 net income - just the same as if you'd originally paid 40% tax. (This ignores the effect of investment growth, but if you would have saved the £60 in an ISA, the end result is the same: if you had growth of say 50% over the time the money was in your pension, it'll be the same effect if you had £100 growing to £150 and now received 60% of it, or if you had £60 growing to £90 untaxed in an ISA.) The 55% lump sum charge is in case you are paying 40% tax when you take it out, to make sure that it's not a more attractive option than the 25%+income tax: if you have £100, either you get £45 tax free via a lump sum, or you get £75 gross and hence £45 net. I haven't covered lots of cases here: defined benefit pensions. Roughly, when you start receiving the pension, 20x the initial income from the pension is deemed to crystallise under BCE 2 and any lump sum you receive crystallises under BCE 6. In the former case, you could end up having to pay the LTA charge with money you haven't actually got yet, and you can ask the pension administrator to instead reduce your pension to pay it. However, there are lots of special cases for defined benefit pensions, mostly for historical reasons, so you should make sure you check with your pension administrator about this. if you die before age 75, at which point the LTA test is applied via either BCE 5C/5D, or BCE 7. After paying the LTA charge if any, your dependents or whoever else you leave it to gets the remainder tax-free. transferring overseas (BCE 8). \"\"scheme pensions\"\" under BCE 2 and BCE 3 (I think these are relatively uncommon) some corner cases covered by regulations (BCE 9)\"","title":""},{"docid":"481475","text":"I have had pension programs with two companies. The first told you what your benefit would be if you retired at age X with Y years of service. Each year of service got you a percentage of your final years salary. There was a different formula for early retirement, and there was an offset for social security. They were responsible for putting enough money away each year to meet their obligations. Just before I left they did add a new feature. You could get the funds in the account in a lump sum when you left. If you left early you got the money in the account. If you left at retirement age you got the money that was needed to produce the benefit you were promised. Which was based on current interest rates. The second company had a plan where they published the funding formula. You knew with every quarterly statement how much was in your account, and what interest it had earned, and what benefit they estimated you would receive if you stayed until retirement age. This fund felt almost like a defined contribution, because the formula was published. If most people took the lump sum that was the only part that mattered. Both pension plans had a different set of formulas based on marriage status and survivor rules. The interest rates are important because they are used to determine how much money is needed to produce the promised monthly benefit. They are also used to determine how much they need to allocate each year to cover their obligations. If you can't make the math work you need to keep contacting HR. You need to understand how much should be flowing into the account each month.","title":""},{"docid":"232700","text":"\"Firstly, you should familiarise yourself with your options for your pension fund. They changed as of 6th April 2015 so it's all quite new. The Government's guidance on it is here. If you haven't already taken a tax-free lump sum from your pension fund, you can take up to 25% totally tax free immediately. That makes getting a house for 40K very accessible. Beyond the 25%, you can take any of it out whenever you want (\"\"flexi-access drawdown\"\" or \"\"lump sum payment\"\", depending on whether you take the 25% out up front or not). That'll be taxed, as if you earned it as income. So if you didn't have any other income, you can take another £10600 without tax this tax year, and then another £10600 or whatever the allowance goes up to next tax year, and so on. Above that you'd have to pay 20% tax until you reach the higher-rate tax threshold at about £40K/year. You say you do have other income so you'll have to take that into account as well when calculating what tax you'd have to pay. If you've reached state pension age that will add some more income, of course. Or, as you suggest, you can buy an annuity. You can do that with some or all of the money, and you can still take the 25% tax-free first. If you do buy an annuity the income from it will all be taxed, but again your personal allowance will apply. Essentially an annuity is the least risky option, particularly if you get one that is uprated with inflation. Uprating with inflation makes the initial income even lower but protects you against cost of living rises as you get older. In exchange for avoiding that risk, you probably lose out on average compared to some more risky options. You might choose to get an annuity large enough to cover your basic needs and take more chances with the rest.\"","title":""},{"docid":"325185","text":"We can't know the future, of course, but we know that on average it's better to invest a lump sum. We can look at some periods of recent history to get a sense of the difference between a lump sum 450k investment and maybe say 5 years of 90k. Using S&P 500 return rates, let's say you started investing on Jan 1, 2008: Here, spreading your investing over 5 years earns you an extra $163k. Starting a year later, the same strategy would earn you $327k less than a lump investment: I looked at some other periods, but the story doesn't change from what we already knew; you can reduce risk of losing a big chunk due to a bad year, but it comes at the cost of potential gains. Perhaps you could make a killing by waiting for the next down-turn and buying on the cheap, or maybe you'll just be wasting time and money as the market enjoys sustained growth. I'd go with a lump, trusting the averages; but you're right, another 2008 with no recovery would suck. As for holding $50k back it depends primarily on your monthly budget, many people suggest a 3-8 month liquid emergency fund, I like 6 months. Go with what you're comfortable with.","title":""}],"string":"[\n {\n \"docid\": \"254245\",\n \"text\": \"What's the present value of using the payment plan? In all common sense the present value of a loan is the value that you can pay in the present to avoid taking a loan, which in this case is the lump sum payment of $2495. That rather supposes the question is a trick, providing irrelevant information about the stock market. However, if some strange interpretation is required which ignores the lump sum and wants to know how much you need in the present to pay the loan while being able to make 8% on the stock market that can be done. I will initially assume that since the lender's APR works out about 9.6% per month that the 8% from the stock market is also per month, but will also calculate for 8% annual effective and an 8% annual nominal rate. The calculation If you have $x in hand (present value) and it is exactly enough to take the loan while investing in the stock market, the value in successive months is $x plus the market return less the loan payment. In the third month the loan is paid down so the balance is zero. I.e. So the present value of using the payment plan while investing is $2569.37. You would need $2569.37 to cover the loan while investing, which is more than the $2495 lump sum payment requires. Therefore, it would be advisable to make the lump sum payment because it is less expensive: If you have $2569.37 in hand it would be best to pay the lump sum and invest the remaining $74.37 in the stock market. Otherwise you invest $2569.37 (initially), pay the loan and end up with $0 in three months. One might ask, what rate of return would the stock market need to yield to make it worth taking the loan? The APR proposed by the loan can be calculated. The present value of a loan is equal to the sum of the payments discounted to present value. I.e. with ∴ by induction So by comparing the $2495 lump sum payment with $997 over 3 x monthly instalments the interest rate implied by the loan can be found. Solving for r If you could obtain 9.64431% per month on the stock market the $x cash in hand required would be calculated by This is equal to the lump sum payment, so the calculated interest is comparable to the stock market rate of return. If you could gain more than 9.64431% per month on the stock market it would be better to invest and take the loan. Recurrence Form Solving the recurrence form shows the calculation is equivalent to the loan formula, e.g. becomes v[m + 1] = (1 + y) v[m] - p where v[0] = pv where In the final month v[final] = 0, i.e. when m = 3 Compare with the earlier loan formula: s = (d - d (1 + r)^-n) / r They are exactly equivalent, which is quite interesting, (because it wasn't immediately obvious to me that what the lender charges is the mirror opposite of what you gain by investing). The present value can be now be calculated using the formula. Still assuming the 8% stock market return is per month. If the stock market yield is 8% per annum effective rate and if it is given as a nominal annual yield, 8% compounded monthly\",\n \"title\": \"\"\n },\n {\n \"docid\": \"4734\",\n \"text\": \"First let's define some terms. Your accrued benefit is a monthly benefit payable at your normal retirement age (usually 65). It is usually a life-only benefit but may have a number of years guaranteed or may have a survivor piece. It is defined by a plan formula (ie, it is a defined benefit). A lump sum is how much that accrued benefit is worth right now. Lump sums are based on applicable interest rates and mortality tables specified by the IRS (interest rates are released monthly, mortality annually). Your plan can either use the same interest rates for a whole year, or they can use new ones each month. Affecting your lump sum is whether your accrued benefit is payable now (immediately, you are age 65), or later (deferred, you are now age 30). For example, instead of being paid an annuity assume you are paid just one payment of $1,000 on your 65th birthday. The lump sum of that for a 65 year old would be $1,000 since there would be no interest discount, and no chance of dying before payment. For a 30 year old, at 4% interest the lump sum would be about $237 (including mortality discount). At age 36 the lump sum is $246. So the lump sum will get bigger just because you get older. Very important is the interest discount. At age 30 in the example, 2% interest would produce a $467 lump sum. And at 6% $122. The bigger the rate, the smaller the lump sum because interest helps an amount now grow bigger in the future. To complicate things, since 2008 the IRS bases lump sums on 3 different interest rates. The monthy annuity payments made within 5 years of the lump sum date use the 1st rate, past 5 and within 20 years use the 2nd rate, and past that use the 3rd rate. Since you are age 30, all of your monthly annuity payments would be made after 20 years, so that makes it simple since we'll only have to look at the 3rd rate. When you reach age 45 the 2nd rate will kick in. Here is the table of interest rates published by the IRS: http://www.irs.gov/Retirement-Plans/Minimum-Present-Value-Segment-Rates You'll find your rates above on the 2013 line for Aug-12. That means your lump sum is being made in 2013 and it is being based on the month August 2012. Most likely your plan will use the same rates for its entire plan year. But what is your plan year? If it is the calendar year, then you would have a 5 month lookback for the rates. But if is a September to August plan year with a 1 month lookback, the rates would have changed between August and September. Your August lump sum would be based on 4.52%, your September on would be based on 5.58% (see the All line for Aug-13). For comparison, a 30 year old with a $100 annuity payable at age 65 would have a lump sum value of $3,011 at 4.52%, but a lump sum value of $1,931 at 5.58%. The change in your accrued benefit by month will obviously have some impact on the lump sum value, but not as much as the change in interest rates if there is one. The amount they actually contribute to the plan has nothing to do with the value of the lump sum though.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"188384\",\n \"text\": \"\\\"I got $3394.83 The first problem with this is that it is backwards. The NPV (Net Present Value) of three future payments of $997 has to be less than the nominal value. The nominal value is simple: $2991. First step, convert the 8% annual return from the stock market to a monthly return. Everyone else assumed that the 8% is a monthly return, but that is clearly absurd. The correct way to do this would be to solve for m in But we often approximate this by dividing 8% by 12, which would be .67%. Either way, you divide each payment by the number of months of compounding. Sum those up using m equal to about .64% (I left the calculated value in memory and used that rather than the rounded value) and you get about $2952.92 which is smaller than $2991. Obviously $2952.92 is much larger than $2495 and you should not do this. If the three payments were $842.39 instead, then it would about break even. Note that this neglects risk. In a three month period, the stock market is as likely to fall short of an annualized 8% return as to beat it. This would make more sense if your alternative was to pay off some of your mortgage immediately and take the payments or yp pay a lump sum now and increase future mortgage payments. Then your return would be safer. Someone noted in a comment that we would normally base the NPV on the interest rate of the payments. That's for calculating the NPV to the one making the loan. Here, we want to calculate the NPV for the borrower. So the question is what the borrower would do with the money if making payments and not the lump sum. The question assumes that the borrower would invest in the stock market, which is a risky option and not normally advisable. I suggest a mortgage based alternative. If the borrower is going to stuff the money under the mattress until needed, then the answer is simple. The nominal value of $2991 is also the NPV, as mattresses don't pay interest. Similarly, many banks don't pay interest on checking these days. So for someone facing a real decision like this, I'd almost always recommend paying the lump sum and getting it over with. Even if the payments are \\\"\\\"same as cash\\\"\\\" with no premium charged.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"407726\",\n \"text\": \"\\\"An annuity is a product. In simple terms, you hand over a lump sum of cash and receive an agreed annual income until you die. The underlying investment required to reach that income level is not your concern, it's the provider's worry. So there is a huge mount of security to the retiree in having an annuity. It is worth pointing out that with simple annuities where one gives a lump sum of money to (typically) an insurance company, the annuity payments cease upon the death of the annuitant. If any part of the lump sum is still left, that money belongs to the company, not to the heirs of the deceased. Fancier versions of annuities cover the spouse of the annuitant as well (joint and survivor annuity) or guarantee a certain number of payments (e.g. 10-year certain) regardless of when the annuitant dies (payments for the remaining certain term go to the residual beneficiary) etc. How much of an annuity payment the company offers for a fixed lump sum of £X depends on what type of annuity is chosen; usually simple annuities give the maximum bang for the buck. Also, different companies may offer slightly different rates. So, why should one choose to buy an annuity instead of keeping the lump sum in a bank or in fixed deposits (CDs in US parlance), or invested in the stock market or the bond market, etc., and making periodic withdrawals from these assets at a \\\"\\\"safe rate of withdrawal\\\"\\\"? Safe rates of withdrawal are often touted as 4% per annum in the US, though there are newer studies saying that a smaller rate should be used. Well, safe rates of withdrawal are designed to ensure that the retiree does not use up all the money and is left destitute just when medical bills and other costs are likely to be peaking. Indeed, if all the money were kept in a sock at home (no growth at all), a 4% per annum withdrawal rate will last the retiree for 25 years. With some growth of the lump sum in an investment, somewhat larger withdrawals might be taken in good years, but that 4% is needed even when the investments have declined in value because of economic conditions beyond one's control. So, there are good things and bad things that can happen if one chooses to not buy an annuity. On the other hand, with an annuity, the payments will continue till death and so the retiree feels safer, as Chris mentioned. There is also the serenity in not having to worry how the investments are doing; that's the company's business. A down side, of course, is that the payments are fixed and if inflation is raging, the retiree still gets the same amount. If extra cash is needed one year for unavoidable expenses, the annuity will not provide it, whereas the lump sum (whether kept in a sock or invested) can be drawn on for the extra expense. Another down side is that any money remaining is gone, with nothing left for the heirs. On the plus side, the annuity payments are usually larger than those that the retiree will get via the safe rate of withdrawal method from the lump sum. This is because the insurance company is applying the laws of large numbers: many annuitants will not survive past their life expectancy, and their leftover monies are pure profit to the insurance company, often more than enough (when invested properly by the company) to pay those old codgers who continue to live past their life expectancy. Personally, I wouldn't want to buy an annuity with all my money, but getting an annuity with part of the money is worthwhile. Important: The annuity discussed in this answer is what is sometimes called a single-premium or an immediate annuity. It is purchased at the time of retirement with a single (large) lump sum payment. This is not the kind of annuity that is described in JAGAnalyst's answer which requires payment of (much smaller) premiums over many years. Search this forum for variable annuity to learn about these types of annuities.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"487621\",\n \"text\": \"So my advice for your financial situation depends on your aims. Are you aiming to: - Completely clear your debt - Clear one card to free up more monthly income. - Clear some debt to allow further controlled spending - Clear one card and focus on just using one, having 2nd as emergency. There are other things you may wish to do but you said to pay off some / all of 2 credit card bills. If you want to contact me I can plan this more precisely. Some seem the same but other factors can come into play as well. Differing rates of interest make the options clearer. My first advice would be to call the card companies and see if you can get better rates first. SCENARIO (some figures made up for visual) Credit Card Debts 8,000 8,000 Monthly payment 100 100 APR % 10 10 Ignoring APR this will be 80 months to repay (otherwise 140 months using my example amounts above) £28,000 repaid over 11 years 8 months. Your Suggestion As per your suggestion originally, paying off cards equally will allow smaller debt on both cards. Credit Card Debt 3,000 3,000 Monthly payment 100 100 APR % 10 10 With a 0% APR this would be paid off in 2 years 6 months. Cards are available to get free balance transfers, need to look into this. With the 10% APR this would take 3 years 1 month. £10,000 lump and £7,400 repaid over 3 years 1 month (saving £10,600 and 8 years 7 months) AIM: To clear debt completely. My advice here is to use the £10,000 lump sum to pay off one credit card, the remaining £2,000 can then come off the other card. This will free up your outgoings (was 2 x £100) by £100. But then use this £100 to pay off the card, this will result in the following: Credit Card Debt 6,000 Monthly payment 200 APR % 10 With a 0% APR this would be paid off in 2 years 6 months. Cards are available to get free balance transfers, need to look into this. With 10% APR this would take roughly 3 years 1 month. £10,000 lump and £7,400 repaid over 3 years 1 month (saving £10,600 and 8 years 7 months). This option is the same as above, but you have the options on the odd tight month to reduce payments to £100. This also will allow the 2nd card to be used interest free for an emergency purchase (to be paid off without any interest charge) If rates are different, pay of the one with the higher APR AIM: Clear one card to free up more monthly income. AIM: Clear one card and focus on just using one, having 2nd as emergency. Same as above, but don’t increase to £200, leave monthly payment at £100. Credit Card Debt 6,000 Monthly payment 100 APR % 10 With a 0% APR this would be paid off in 5 years. With the 10% APR this would take 88 months (7 years 4 months) £10,000 lump and £8,800 repaid over 7 years and 4 months (saving £9,200 and 4 years 4 months). This also allows for some extra spending (even racking back up the debt – although not advised) AIM: Clear some debt to allow further controlled spending As above apart from this will allow you to spend to get back up to full £16,000 debt. NOTE My figures are theoretical, paying off £500 (£250x2) a month instead of the £100 (10%APR) would take: Lump sum 10,000, remaining 6,000 – 14 months (£17,000 paid) Lump sum 5,000, remaining 2 x 5,500 – 26 months (£18,000 paid) Lump Sum 0, remaining 2 x 8,000 – 40 months (£20,000 paid) Now I have finished waffling, I hope you have an idea on what you are aiming to achieve and a better idea of what to do when you receive the income Stephen.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"323238\",\n \"text\": \"Have her pay something like a friendly monthly rent. This should be less than half of the monthly mortgage cost, since you are assuming the risk (and benefits) of a mortgage and closer to the rent of similar places near you. For when you get married and she is to have half the apartment, have a pre-agreed way to calculate a lump-sum that she needs to provide to match your own contributions up to that time, as if you two had equal contributions from the beginning. The financially precise way to do it would be to have her pay more than the mere sum of the amount (since she will be providing the amount at a later time than you), but I would be generous and skip this in your place if the difference is not too big. If you break up, she will have payed what would be a fair amount of rent, as if you two were renting, so, in this sense, it is fair that she would not have a claim on the apartment. In case that you two would like that she keeps the apartment, you can just sell it to her, having her pay this same amount as above and assume responsibility for the rest of the mortgage.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"432280\",\n \"text\": \"\\\"This is a bit pornographic, isn't it, in that we're looking at something we'd like to do (namely, \\\"\\\"win the big lottery!\\\"\\\") but probably won't ever have this happen to us. :) Anyway. Ignoring the fact that this is kind of a hypothetical question... Gotta go with The Straight Dope on this one, when deciding whether to take an annuity or a lump sum: What assumed interest rate is underlying the calculations? Do you think you can earn significantly more than that rate on your own? If so, take the lump sum cash value. If not, go with the annuity. What are your financial needs, both immediate and over the next twenty years? Do you need a steady flow of income? If you take the lump sum and invest it poorly or lose it, how much will it hurt you? If you give up your job to enjoy your wealth, what will happen if you're still alive when the annuity payments stop? You don't want to blow it all in a spree and then find yourself in poverty in your old age. What happens if you die before the annuity has been fully paid? As noted, there's the question of whether to ask in advance for an annuity - the tax treatment alone could overwhelm any other considerations.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"8601\",\n \"text\": \"Setting aside for the moment the very relevant issue of whether you need the full amount quickly, I'll just tackle comparing which option gives you to maximum amount of money (in terms of real dollars). The trick is, unless you think inflation will suddenly reverse itself or stop entirely (not likely), $50K today is worth a LOT more than $50K in 20 years. If you don't believe me, consider that just 30 years ago the average price for a mid-level new car was around $3k. When you grandfather says he got a burger for a nickel, he isn't talking about 2010 dollars. So, how do you account for this? Well, the way financial people and project managers do it to estimate how much to pay today for $1 at some point in the future is through a net present value (NPV) calculation. You can find a calculator here. In your question, you gave some numbers for the payout, but not the lump sum prize amount. Going solely on what you have provided, I calculate that you should take the lump sum if it is greater than $766,189.96 which is the net present value of 20 years of $50K Payments assuming 3% annual inflation, which is fairly a fairly reasonable number given history. However, if you think the out-of-control Gov't spending is going to send inflation through the roof (possible, but not a given), then you almost certainly would want the lump sum. I suppose in that scenario you might want the lump sum anyway because if the Govt starts filching on their obligations, doing it to a small number of lottery winners might be politically more popular than cutting other programs that affect a large number of voters.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"559745\",\n \"text\": \"\\\"@fredsbend, Hope this helps! \\\"\\\"I understand that a reverse mortgage can be paid out in two ways: A lump sum and monthly payments. I figure that if you take the lump sum, eventually, the bank wants you to start paying it back.\\\"\\\" Answer: Actually, there are 3 payout options, or 4 if you consider a combination payout as another one. There's a lump sum, a line of credit, or the monthly payout, or a combination. \\\"\\\"I figure that if you take the monthly payments, eventually, the bank stops paying out and wants you to pay it back. In both situations, interest accrues and this is how the bank makes money off of the deal\\\"\\\". Answer: The only time the monthly payments would stop would be if the borrower defaults on the lenders' terms or they no longer live at home. You are right though, and interest does accrue on whichever payment is decided on. I'm not sure how the lender makes money, probably by the interest, but I know borrowers are protected against high rates and owing more than your house. Here's an article I found that goes over the protections more in detail: https://www.americanadvisorsgroup.com/news/6-consumer-protections-reverse-mortgage-loan-borrowers. \\\"\\\"But what determines when you have to begin paying back the reverse mortgage? Some sources online seem to say that it's based only on if you die or would like to sell/move. That can't be right in all situations, because you could end up with a massive debt on a property more than its value.\\\"\\\" Answer: There are a lot of protections or regulations in place to protect anyone who takes out a reverse mortgage. One being, you can't owe MORE than your house is valued at during the time of repayment, a reverse mortgage is a non-recourse loan. In the instance that your house is less than you owe, you either sell the home and the proceeds are used to pay the loan and you keep the rest OR if you owe more than the house proceeds of the home go to the lender. Either way, you're not left paying for a \\\"\\\"mortgage\\\"\\\" without the house. In the case the parent, grandparent passes, then the heirs would have a choice of either paying back the reverse mortgage in payments, OR they can sell the house, heirs are protected during this as well to make sure they're not left with major debt in case of anything. Is there a formula to figure out when the bank stops the monthly payments and then wants it back? **Answer:**The amount becomes due if loan terms are not met, but the lender will discuss the options if it comes to that. Is there a different formula for when the lump sum would have to be paid back?\\\"\\\" Answer: Each payout option has the same terms and the same pay back terms. As long as terms are met, the lender can't ask for early repayment.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"391583\",\n \"text\": \"Retirement calculation, in general, should be based on the amount of money needed per year/month and the expected life expectancy. Life expectancy, if calculated to 90 years (let's say) indicates that post retirement age (60 yrs.) your accumulated/invested money should generate adequate income to cover your expenses till 90 years. The problem in general is not how long you shall live but what would be your expected spending from retirement to end of life expectancy. The idea is at the minimum your investments should generate income that is inflation adjusted. One way to do this is to consider your monthly expense now i.e. the expense that is absolute minimum for carrying on (food, electricity, water, medicines, household consumables, car petrol, insurance, servicing, entertainment, newspaper etc.) this does not contain the amortizable liabilities (home loan, child's education, other debts). It is better to take this amount per family rather than per person and yearly rather than monthly (as we tend to miss a lot of yearly expenses). This amount that you need today will increase at a Compounded Annual Growth Rate (CAGR) of the average inflation. For example, if today you spend 100 per year in 7 years you will need to spend appx. 200 at 10% inflation. Now, your investments will not increase post your retirement, so your current investment needs to do two things (1) give you your yearly requirement (2) grow by a fixed amount so that next year it can give you CAGR adjusted returns. In general, this kind of investment grows by high net amounts initially and slowly the growth decrease. The above can be calculated by Net Present value (NPV) formulae (http://en.wikipedia.org/wiki/Net_present_value). The key is to remember that the money that is invested when you retire should be able to give you inflation adjusted returns to cover your yearly expenses. How much money you need depends on your life style/expectation and how much return is received depends on the instruments that you invest on. As for your question above on the difference between the age of you and your spouse, it better to go with the consolidated family requirement and get an idea of how much investment is necessary and provision the same as soon as possible from your as well as your spouse's income. Hope this helps.- thanks\",\n \"title\": \"\"\n },\n {\n \"docid\": \"180071\",\n \"text\": \"\\\"There are two options (according to Wells Fargo). You can either apply for a Business/Commercial Equity Loan or a Line of Credit. A loan is what it sounds like - they give you a lump sum of money for you to use and you have to pay it in monthly installments. A line of credit is like a credit card, you have money that you can borrow (up to a certain amount) and you have to make monthly payments. The process can differ for different business, they probably look at what your real estate is worth, how much money you are generating from it, etc. I am not recommending or endorsing Wells Fargo, other major banks offer the same types of products, Wells Fargo just happened to appear first when I searched for \\\"\\\"business line of credit\\\"\\\".\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"539112\",\n \"text\": \"\\\"The specific \\\"\\\"State Pension\\\"\\\" plan you have linked to is provided by the government of the U.K. to workers resident there. More generally speaking, many countries provide some kind of basic worker's pension (or \\\"\\\"social security\\\"\\\") to residents. In the United States, it is called (surprise!) \\\"\\\"Social Security\\\"\\\", and in Canada most of us call ours \\\"\\\"Canada Pension Plan\\\"\\\". Such pensions are typically funded by payroll deductions distinct & separate from income tax deducted at source. You can learn about the variety of social security programs around the world courtesy of the U.S. Social Security Administration's own survey. What those and many other government or state pensions have in common, and the term or concept that I think you are looking for, is that they are typically defined benefit type of plans. A defined benefit or DB plan is where there is a promised (or \\\"\\\"defined\\\"\\\") benefit, i.e. a set lump sum amount (such as with a \\\"\\\"cash balance\\\"\\\" type of DB plan) or income per year in retirement (more typical). (Note: Defined benefit plans are not restricted to be offered by governments only. Many companies also offer DB plans to their employees, but DB plans in the private sector are becoming more rare due to the funding risk inherent in making such a long-term promise to employees.) Whereas a defined contribution or DC plan is one where employee and/or employer put money into a retirement account, the balance of which is invested in a selection of funds. Then, at retirement the resulting lump sum amount or annual income amounts (if the resulting balance is annuitized) are based on the performance of the investments selected. That is, with a DC plan, there is no promise of you getting either a set lump sum amount or a set amount of annual income at retirement! The promise was up front, on how much money they would contribute. So, the contributions are defined (often according to a matching contribution scheme), yet the resulting benefit itself is not defined (i.e. promised.) Summary: DB plans promise you the money (the benefit) you'll get at retirement. DC plans only promise you the money (the contributions) you get now.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"217222\",\n \"text\": \"The equation is the same one used for mortgage amortization. You first want to calculate the PV (present value) for a stream of $50K payments over 20 years at a10% rate. Then that value is the FV (future value) that you want to save for, and you are looking to solve the payment stream needed to create that future value. Good luck achieving the 10% return, and in knowing your mortality down to the exact year. Unless this is a homework assignment, which need not reflect real life. Edit - as indicated above, the first step is to get that value in 20 years: The image is the user-friendly entry screen for the PV calculation. It walks you though the need to enter rate as per period, therefore I enter .1/12 as the rate. The payment you desire is $50K/yr, and since it's a payment, it's a negative number. The equation in excel that results is: =PV(0.1/12,240,-50000/12,0) and the sum calculated is $431,769 Next you wish to know the payments to make to arrive at this number: In this case, you start at zero PV with a known FV calculated above, and known rate. This solves for the payment needed to get this number, $568.59 The excel equation is: =PMT(0.1/12,240,0,431769) Most people have access to excel or a public domain spreadsheet application (e.g. Openoffice). If you are often needing to perform such calculations, a business finance calculator is recommended. TI used to make a model BA-35 finance calculator, no longer in production, still on eBay, used. One more update- these equations whether in excel or a calculator are geared toward per period interest, i.e. when you state 10%, they assume a monthly 10/12%. With that said, you required a 20 year deposit period and 20 year withdrawal period. We know you wish to take out $4166.67 per month. The equation to calculate deposit required becomes - 4166.67/(1.00833333)^240= 568.59 HA! Exact same answer, far less work. To be clear, this works only because you required 240 deposits to produce 240 withdrawals in the future.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"17633\",\n \"text\": \"There can be Federal estate tax as well as State estate tax due on an estate, but it is not of direct concern to you. Estate taxes are paid by the estate of the decedent, not by the beneficiaries, and so you do not owe any estate tax. As a matter of fact, most estates in the US do not pay Federal estate tax at all because only the amount that exceeds the Federal exemption ($5.5M) is taxable, and most estates are smaller. State estate taxes might be a different matter because while many states exempt exactly what the Federal Government does, others exempt different (usually smaller) amounts. But in any case, estate taxes are not of concern to you except insofar as what you inherit is reduced because the estate had to pay estate tax before distributing the inheritances. As JoeTaxpayer's answer says more succinctly, what you inherit is net of estate tax, if any. What you receive as an inheritance is not taxable income to you either. If you receive stock shares or other property, your basis is the value of the property when you inherit it. Thus, if you sell at a later time, you will have to pay taxes only on the increase in the value of the property from the time you inherit it. The increase in value from the time the decedent acquired the property till the date of death is not taxable income to you. Exceptions to all these favorable rules to you is the treatment of Traditional IRAs, 401ks, pension plans etc that you inherit that contain money on which the decedent never paid income tax. Distributions from such inherited accounts are (mostly) taxable income to you; any part of post-tax money such as nondeductible contributions to Traditional IRAs that is included in the distribution is tax-free. Annuities present another source of complications. For annuities within IRAs, even the IRS throws up its hands at explaining things to mere mortals who are foolhardy enough to delve into Pub 950, saying in effect, talk to your tax advisor. For other annuities, questions arise such as is this a tax-deferred annuity and whether it was purchased with pre-tax money or with post-tax money, etc. One thing that you should check out is whether it is beneficial to take a lump sum distribution or just collect the money as it is distributed in monthly, quarterly, semi-annual, or annual payments. Annuities in particular have heavy surrender charges if they are terminated early and the money taken as a lump sum instead of over time as the insurance company issuing the annuity had planned on happening. So, taking a lump sum would mean more income tax immediately due not just on the lump sum but because the increase in AGI might reduce deductions for medical expenses as well as reduce the overall amount of itemized deductions that can be claimed, increase taxability of social security benefits, etc. You say that you have these angles sussed out, and so I will merely re-iterate Beware the surrender charges.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"197576\",\n \"text\": \"First of all depending on the type of IRA you may not have to pay taxes on withdrawals in the US at all. If you are withdrawing your principle from a Roth IRA then you don't owe taxes. Only when you withdraw the gains do you pay taxes on it. You have two options for withdrawals: Lump Sum Withdrawal: If you take a lump sum withdrawal you will owe taxes to the US (30% for non-resident aliens of the US), and according to DTAA; Article 23, you will file your taxes with India declaring your IRA or 401(k) withdrawal proceeds and claim credit on the taxes you paid to the US. Monthly Pension Withdrawal: You can also receive monthly pension payments and you will only be taxed in the country in which you are a resident of. This is according to DTAA, Article 20. You would then have to submit necessary documentation to your payer in the US so that they do not withhold any taxes in the US. Just as a side note it might be just better to keep the money where it is and let it grow or roll it over to a Roth IRA if you are currently in a lower tax bracket for maximum savings of your principle. Here is a link with more detailed information of what I provided you: http://articles.economictimes.indiatimes.com/2012-01-25/news/30663129_1_taxable-income-nri-401k-plan\",\n \"title\": \"\"\n },\n {\n \"docid\": \"465283\",\n \"text\": \"After some thought, I follow Dave Ramsey's advice because it's simple and I can do the math in my head - no online calculator needed. :) You need Life Insurance if someone depends on your income. You can replace your income with a single lump sum of 8-10 times your current income where those who need your income, can get roughly your salary each year from the life insurance proceeds.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"34538\",\n \"text\": \"\\\"Some details in case you are interested: Being a defined benefit kind of pension plan, the formula for your Social Security benefits isn't tied directly to FICA contributions, and I'm not aware of any calculator that performs an ROI based on FICA contributions. Rather, how much you'll get in retirement is based on your average indexed monthly earnings. Here's some information on the Social Security calculation from the Social Security Administration - Primary Insurance Amount (PIA): For an individual who first becomes eligible for old-age insurance benefits or disability insurance benefits in 2013, or who dies in 2013 before becoming eligible for benefits, his/her PIA will be the sum of: (a) 90 percent of the first $791 of his/her average indexed monthly earnings, plus (b) 32 percent of his/her average indexed monthly earnings over $791 and through $4,768, plus (c) 15 percent of his/her average indexed monthly earnings over $4,768. Here's an example. Of course, to calculate a benefit in the future, you'll need to calculate projected average indexed monthly earnings; more details here. You'll also need to make assumptions about what those bend points might be in the future. The average wage indexing values for calculating the AIME are available from the Social Security Administration's site, but future indexing values will also need to be projected based on an assumption about their inflation. You'll also need to project the Contribution and Benefit Base which limits the earnings used to calculate contributions and benefits. Also, the PIA calculation assumes benefits are taken at the normal retirement age. Calculating an early or late retirement factor is required to adjust benefits for another age. Then, whatever benefits you get will increase each year, because the benefit is increased based on annual changes in the cost of living. Performing the series of calculations by hand isn't my idea of fun, but implementing it as a spreadsheet (or a web page) and adding in some \\\"\\\"ROI based on FICA contributions\\\"\\\" calculations might be an interesting exercise if you are so inclined? For completeness sake, I'll mention that the SSA also provides source code for a Social Security Benefit Calculator.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"320362\",\n \"text\": \"\\\"You'd need to talk with an attorney familiar with Social Security, or an appropriately qualified SSA representative to be sure - but all signs point to the idea that unfortunately Social Security does not work the way your father was told it would. And if he doesn't file to receive benefits the reality is actually much worse than \\\"\\\"throwing away free money\\\"\\\"! However, this is not due to a complete misunderstanding of the system! Social Security does work the way he thinks in some instances, just that the rules don't apply to his exact situation! First of all, retroactive benefits come in a few forms: File and suspend to get a lump only if you really need it - BEFORE the age of 70 only! In this method you apply for retirement, but you tell the SSA to suspend/delay your benefits. You are entitled to full lump sum of the payments you deferred...but at a cost of getting lower monthly benefits permanently (and that also lowers spousal and dependent children's benefits, too - if those could apply to your dad). But note that at the age of 70, Social Security will stop deferring the payments and start paying you the full maximum retirement benefit monthly, with no lump sum. This is a kind of emergency insurance policy for those who want to try to defer retirement benefits, but who want the opportunity to cash out and get the money they would have been getting \\\"\\\"just in case\\\"\\\". You can get up to 6 months of retroactive benefits, such as if you wait past your exact retirement age to apply for benefits. But no more: \\\"\\\"we cannot pay retroactive benefits for any month before you reached full retirement age or more than 6 months in the past\\\"\\\". As for after-death benefits, an estate can only get benefits that were already due to be paid, which generally means a person died and did not get their benefits for that month, so SSA can re-issue a check to the estate following these rules. But as a person cannot be due a lump sum payment after age 70 (for more than 6 months at most), the estate will only be able to get at most 1-6 months of payments (and 6 months is doubtful - you'll need to ask a lawyer if that much would even be possible). If your father was below 70 and wanted to file-and-suspend, the question of lump on death would be more complex and I don't know that answer - but once you are past 70 this doesn't matter any more as you aren't due a lump anymore. Given the above, we've established pretty clearly that if you don't claim your benefits within 6 months after age 70, any months of payment you would have gotten are just forfeited to the system. But if you claim the benefits and stick them in the bank, can they be taken? Well, if a lawsuit is really a worry, then yes these accumulated funds can required to pay a debt - but this potential for loss can be protected against without forfeiting the benefits entirely! This is not very common, but if your father doesn't need the money now he may be able to deposit some of the money into a special partially-lawsuit protected format of the Roth IRA (which has no age limits) as detailed here. If he never gets sued, that's OK - it's still his money! If he passes away, the value goes to his estate and does not disappear. And he doesn't forfeit any of his earned retirement benefits. Finally, I would like to share one last thing with you and your father. These benefits aren't free - he has been paying a portion of his paycheck for decades into Social Security, and now he is eligible for the maximum amount of benefits per month that he will qualify for - and if he wants to keep working he loses no benefit and the amount could potentially even go up. That's up to him. But not filing for benefits now will mean that all this money he's been paying in for decades will just be lost - they'll basically just be a tax he's paid out to other retirees. His estate (which means you kids) won't get any of it, either. That'd just be a waste for everyone involved. If you have continued doubts or questions, I wouldn't hesitate to consult a specialist lawyer or talk with the SSA directly to make sure this is all correct. It's his money, and he has earned his benefits for many years. I very much hope he gets to enjoy as much of them as he can!\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"308010\",\n \"text\": \"As mentioned in other answers the interest you make is negligible and the calculations would depend on the bank. In saying that the general trend is calculate daily, pay monthly. A typical scenario would be that every night at midnight the interest for your account at that point in time is calculated. This occurs every midnight and at the end of the month the sum of those calculations will be added to your account. You could have had several significant transactions pass through your account in one day although if the interest is calculated at a specific point in time some transactions may not contribute to any interest. These calculations are worth thinking about, even in circumstances of negligible returns, as it could assist when considering combining credit cards with home loan offset accounts so it is not a complete waste of time to understand how interest is calculated. The more you know ;)\",\n \"title\": \"\"\n },\n {\n \"docid\": \"181732\",\n \"text\": \"\\\"You can use the 6900 to make an investment. Or to buy something. That's why people keep reminding you that you could make interest. Because most people think of either 7200 now or paying the same 7200 over time. So you could just be storing the 7200 under the mattress until you pay it out. Obviously in that case, inflation doesn't matter (\\\"\\\"is not applicable\\\"\\\"). You've given up the use of the 7200 from the beginning. Think of it instead as 7200 now and twenty-three payments of 300 each. So 14,100 total. Then you can spend 6900 on something else at the beginning or spend 300 a month on other things. The difference between spending 6900 now and 300 in each of twenty-three months would be measured in inflation. Of course, this requires you to have both 7200 now and an income stream producing at least 300 a month. Another way of doing things is to take 6900 and invest it. Each month you remove 300 and use it to make a payment. We're now back to just one 7200, plus the interest over time. I would argue that this is still an inflation advantage. It's just that instead of spending the money, you invested it. And that of course is your prerogative. The point being that you would not have that opportunity if you paid up front. Now to calculate the difference in monthly payments of 300 euro using the above webpage what should I do? As already said, you would have to calculate twenty-three values and then sum them with the 300 you pay up front in the monthly. There are other ways to calculate it, if you are not using that particular tool. For example, there are formulas to calculate the net present value of an annuity. E.g. see Investopedia. Where: P = the present value of an annuity stream PMT = the dollar amount of each annuity payment r = the inflation rate n = the number of periods in which payments will be made Investopedia talks about interest rates, but you can put inflation there for this purpose. In that case, r might better be called the \\\"\\\"discount rate\\\"\\\". PMT is 300. r is whatever estimate you are using for inflation. E.g. .003 per period. n is 23. Note that the monthly inflation rate is smaller than the annual rate. So .003 is about 3.66% annually. 3.04% annually is more like .0025 a month. I found calculators for this with search terms \\\"\\\"present value of annuity calculator\\\"\\\". Some of the calculators will take the annual rate (3.66%) and number of periods per year as input. Or the calculator may take a monthly rate as a percentage (.3%) rather than as a decimal (.003). So be careful of the inputs. This gives me a net present value (NPV) of 6,657.69 for the 23 payments of 300, assuming .3%. Or 6957.69 is the NPV of the monthly payments and 7200 is the NPV of the 7200 up front. Obviously if you can pay less than 6957.69 up front rather than 7200, then it makes more sense to pay up front. Even without a discount though, it still may make more sense to pay up front. How much those intangibles are worth is up to you.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"131451\",\n \"text\": \"\\\"For example, for my employer I received a signing bonus, and a \\\"\\\"relocation lump sum\\\"\\\" separate from that signing bonus. The relocation lump sum is taxed and will appear as income on my W-2, and I can spend it on anything I want. That said, should the relocation lump sum count towards the entry quoted above in Form 3903, or would it be considered the same as any other bonus; thus allowing me to take a full deduction for all of my deductible travel expenses? The signing bonus and relocation lump sum will appear as regular income on your W-2. You can think of the relocation bonus as something to cover the pain and suffering the cost of moving, without needing to send in receipts. Lets assume that you meet the distance and time tests, so there is potential to save money on your taxes. Lets also put your actual moving expenses as $2500. If you have valid moving expenses the IRS will allow you to use them to reduce your AGI. So now you can reduce your AGI by the $2500. Enter the total amount your employer paid you for the expenses listed on lines 1 and 2 that is not included in box 1 of your Form W-2 (wages). This amount should be shown in box 12 of your Form W-2 with code P. My question is: what exact payments from your employer should be entered here? I realize that you can just write the number you get in box 12 with code P on your W-2, but I'm curious how they come up with this number. In some cases the company will reimburse you your moving expenses up to a maximum of $x. For example a maximum of $1000 That means you submit receipts for those expenses and they give you a check or add it to your next paycheck. The check will either be for the amount on your receipts or the maximum amount, whichever is smaller. In this situation with actual expenses of $2500 and a reimbursement of $1000 you can reduce your AGI by $1500.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"270022\",\n \"text\": \"As I see it the two main considerations are: Total amount of money received, for which the key variable is life expectancy. 41000 * 0.8 = 32800, so at £86 / week she would only be better off with the lump sum if she expected to live for less than ~7.3 years. Obviously none of us have a crystal ball, but you could make some assessment based on her current health, risk factors etc. to see whether that seemed feasible. Also you do have to bear in mind that the value of £86 in 7 years' time will be less than it is now - but I guess the £86 would be inflation adjusted? Her need for income (versus capital). If she takes a lump sum and invests it in a house, that is great but doesn't provide any income at all. If she has sufficient income from other sources (and forecasts this other income to continue until her death) then the lump sum might be more attractive, but if not then she would need to be sure that she wasn't tying up the money unnecessarily. Another option here would be using the lump sum to buy an annuity, and it might be wroth exploring this, but I doubt whether the rates would be good enough to beat the £86 / week she is being offered as an alternative. Another (lesser?) consideration is her future entitlement to state-funded care if needed in her later years. If you have assets above a certain amount you are expected to fund your own care, in which case having an expensive house might actually be more of a liability than a help.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"30935\",\n \"text\": \"\\\"No, I do not. The advice is to take advice :-) but it is not required. Several \\\"\\\"low cost\\\"\\\" SIPPs allow an \\\"\\\"Execution Only\\\"\\\" transfer from some pensions (generally not occupational or defined benefits schemes [where transfers are generally a bad idea anyway] but FAVCs such as mine are ok). Best Invest is one such, and the fees are indeed relatively low. As far as anyone knows, the government's plans for changes to rules on using pension funds would still apply even once I've transferred my pension pot and begun to withdraw funds (provided I don't commit myself to an annuity or other irrevocable investment). I am not a financial adviser, nor employed or otherwise connected with Best Invest, and I'm not endorsing their SIPP schemes, just giving them as an example of what can be done. [Added after I carried out my plan] I found the process very straightforward; I needed to apply for a pension fund with my new provider and fill in a transfer form, which set up the scheme and transferred the funds with no expense required. Once the money arrived in my pension account I filled in another form to take the lump sum and set up regular withdrawals from the fund. I had my lump sum within a couple of months of initiating the transfer. I'm very happy I did not take independent advice because it would have been very poor value for money. During my researches I was approached eagerly by one firm promising to get me my money quick and claiming to be an independent financial advisor. Luckily I mistrusted the service they offered.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"173213\",\n \"text\": \"\\\"Looking at some large lotto games out there, it seems that the lump sum (cash) option comes in at anywhere from about 50 to 70 percent of the jackpot amount (sum of annual payouts, typically over 20 to 30 years). I'm a fan of the phrase \\\"\\\"money today is better than money tomorrow.\\\"\\\" There's no telling how laws will change, taxes will change, if inflation will skyrocket, if you'll die early, if you or a family member will encounter a life-changing event, etc. By taking the lump sum option you trade a percentage of the winnings for the risk of the future unknowns. How much are those unknowns worth to you? The tax implications are something else to consider. In your example of a \\\"\\\"small\\\"\\\" jackpot with $50,000 annual payouts, it's likely that you could still avoid the highest tax bracket each year, whereas taking the lump sum would be taxed at the highest rate (35% of the amount above $373k, for a single filer in 2010). However, this might not make much of a difference for large jackpots with higher annual payouts. With the lump sum option, you also have a greater potential of investment returns (and losses) since you can put all the money to work for you right away. It also allows you to purchase larger assets sooner, if that's something that interests you. In the end, I'd say the reduced risk and the higher return potential of the lump sum option is well worth the reduced payout. I'd also suggest not playing the lottery :)\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"488638\",\n \"text\": \"\\\"Really this is no different from any kind of large lump sum and having a mortgage. There are probably many questions and answers on this subject. It really doesn't matter that the proceeds were the result of a sale, an inheritance would not change the answer. I think it is important to note that the proceeds will not eliminate the house 2 mortgage. A high level choice of investment one makes is between equity (such as stock) and debt investments (such as bonds and mortgages). You are in a unique case of being able to invest in your own mortgage with no investment fee. This may tip the scales in favor of paying down the mortgage. It is difficult to answer in your specific case as we don't know the rest of your finances. Do you have a sizable 401K that is heavily invested in stocks? Do you have the need for a college fund? Do you have an emergency fund? Do you have a desire to own several homes generating income property? If it was me I'd do the following in order, skipping steps I may have already completed: I've heard that the bank may agree to a \\\"\\\"one time adjustment\\\"\\\" to lower the payments on Mortgage #2 because of paying a very large payment. Is this something that really happens? I really kind of hate this attitude. Your goal is to get rid of the mortgage in a timely manner. Doing such makes paying for kids college a snap, reduces the income one might need in retirement, basically eliminates the need for life insurance, and gives one a whole lot of money to have fun with.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"497281\",\n \"text\": \"There are a number of scholarly articles on the subject including a number at the end of the Vanguard article you reference. However, unfortunately like much of financial research you can't look at the articles without paying quite a bit. It is not easy to make a generic comparison between lump-sum and dollar cost averaging because there are many ways to do dollar cost averaging. How long do you average over? Do you evenly average or exponentially put the money to work? The easiest way to think about this problem though is does the extra compounding from investing more of the money immediately outweigh the chance that you may have invested all the money when the market is overvalued. Since the market is usually near the correct value investing in lump sum will usually win out as the Vanguard article suggests. As a side note, while using DCA on a large one time sum of money is generally not optimal, if you have a consistent salary DCA by frequently investing a portion of your salary has been frequently shown to be a very good idea of long periods over saving up a bunch of money and investing it all at once. In this case you get the compounding advantage of investing early and you avoid investing a large chunk of money when the market is overvalued.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"68872\",\n \"text\": \"\\\"Note - this is a complicated topic. I've read the rules multiple times and I'm still not sure I understand them perfectly. So please take this with a pinch of salt and read the rules for yourself. The time(s) at which a test is done against the LTA are known as a \\\"\\\"Benefit Crystallization Event\\\"\\\" (BCE). There are 13 of these (!) - they're numbered 1-9 with the addition of some extras numbered 5A-D. However, the most important ones for those with defined contribution pensions are: Broadly, the idea is that a BCE occurs when you start taking money out of your pension, and when you reach age 75. Each time one happens, the amount you are taking out (\\\"\\\"crystallizing\\\"\\\") gets compared against the LTA and a certain percentage of your LTA gets designated as being used. Crystallising doesn't necessarily mean you actually receive the money immediately, just that some of your money is switched into a mode where you can start receiving it in different ways. The rules are designed to avoid double counting, so broadly anything that was taken off your LTA won't be taken off a second time. The cumulative use of your LTA is tracked as a percentage rather than an absolute amount, to take account of any changes in the LTA between the different times you crystallise money. For example if you crystallise £100K when the LTA is £1mn, that's 10% of your LTA gone. If later on the LTA has risen to £1.1mn and you take out £110K, that's another 10%. Once you hit 100%, you start paying a LTA charge on any excess. The really simple path here is if you just get an annuity with your entire pot, before hitting age 75 (and you don't make any further pension contributions after). Then only BCE 4 applies: your pension pot, all of which is being used to buy the annuity, is compared with the LTA. After this point your entire pension pot is considered to be crystallized, so no more BCEs will apply - the tests at age 75 only apply if you still have money that you haven't taken out or used to buy an annuity. The annuity payments themselves will be subject to income tax at your normal rate at the time you receive them, i.e. 0%, 20%, 40% or 45% depending on how much other income you have. In reality most people would want to take 25% of their pot as a lump sum at the same time as buying an annuity, given that it's tax-free if you're under the LTA. At this point BCE 6 applies in addition to BCE 4, but again the overall effect of the test is pretty simple, look at the total pension pot (lump sum + cost of annuity), and if it's under the LTA you're fine. Again, at this point no more BCEs will apply as all the money is considered to have been fully distributed. If you only use part of the money for an annuity/lump sum, then only that part of the money is compared against the LTA, and the rest stays in your pension and will be compared later. The 25% limit for a tax-free lump sum applies to the total you are taking out at that point: if you have £200K and are taking out £100K, you can take out £25K as a tax-free lump sum and use £75K for the annuity. The other £100K stays in your pension. Many people see annuity rates as very low and will want to take on more risk (and reward) by using \\\"\\\"Drawdown\\\"\\\" for at least part of their pension. Essentially, you can designate part of your pension for drawdown, and at that point BCE 1 applies to the money you designate. Once designated, you can start drawing the money out as income, which will be taxed at your normal income tax rate at the time you receive it. Again, you can take 25% as a lump sum at this point which will be subject to BCE 6. There's also an alternative route where you put everything into \\\"\\\"flexi-access drawdown\\\"\\\" without taking any lump sum immediately, and then as you actually withdraw income, 25% is tax-free and the rest is taxed as income. The overall effect is the same, but it gives you more control over when you get the tax-free bit. However, because with drawdown you can actually leave the money in your pension and growing tax-free, there's a further test against the LTA at age 75 under BCE 5A. To avoid double-counting (\\\"\\\"prevention of overlap\\\"\\\"), the amount left in the drawdown fund at that point is reduced by whatever was previously tested against BCE 1. So if you put £150K into drawdown initially, and it's grown to £200K by age 75, then another £50K will crystallise under BCE 5A. I think that if you put £150K into drawdown initially and it grows by £50K, but you take that out as income so that only £150K (or less) remains at age 75, then the amount crystallising under BCE 5A is nil. Also, when money is in drawdown, you can choose to use it to buy an annuity. BCE 4 is applied at this point (if before age 75), but as with BCE 5A, this is reduced by anything that was previously crystallised under BCE 1. If you only use some of it to buy an annuity, the reduction is pro-rataed, e.g. if you started out with £150K moved into drawdown, and later it has grown to £200K and you use £100K to buy an annuity, then the reduction is £75K so £25K is considered to have crystallised under BCE 4. Once you reach age 75, as well as any money that's still in drawdown, anything you haven't yet crystallised at all gets tested against the LTA under BCE 5B. Broadly, once you go over the LTA, the charges are simple: There's never any explanation given for these two rates, but I think it's all based on trying to at least cancel out the benefit you got from using your pension, on the assumption that: So with the 25% charge + 20% income tax, if you take out £100, you'll end up with £75 gross income, so £60 net income - just the same as if you'd originally paid 40% tax. (This ignores the effect of investment growth, but if you would have saved the £60 in an ISA, the end result is the same: if you had growth of say 50% over the time the money was in your pension, it'll be the same effect if you had £100 growing to £150 and now received 60% of it, or if you had £60 growing to £90 untaxed in an ISA.) The 55% lump sum charge is in case you are paying 40% tax when you take it out, to make sure that it's not a more attractive option than the 25%+income tax: if you have £100, either you get £45 tax free via a lump sum, or you get £75 gross and hence £45 net. I haven't covered lots of cases here: defined benefit pensions. Roughly, when you start receiving the pension, 20x the initial income from the pension is deemed to crystallise under BCE 2 and any lump sum you receive crystallises under BCE 6. In the former case, you could end up having to pay the LTA charge with money you haven't actually got yet, and you can ask the pension administrator to instead reduce your pension to pay it. However, there are lots of special cases for defined benefit pensions, mostly for historical reasons, so you should make sure you check with your pension administrator about this. if you die before age 75, at which point the LTA test is applied via either BCE 5C/5D, or BCE 7. After paying the LTA charge if any, your dependents or whoever else you leave it to gets the remainder tax-free. transferring overseas (BCE 8). \\\"\\\"scheme pensions\\\"\\\" under BCE 2 and BCE 3 (I think these are relatively uncommon) some corner cases covered by regulations (BCE 9)\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"481475\",\n \"text\": \"I have had pension programs with two companies. The first told you what your benefit would be if you retired at age X with Y years of service. Each year of service got you a percentage of your final years salary. There was a different formula for early retirement, and there was an offset for social security. They were responsible for putting enough money away each year to meet their obligations. Just before I left they did add a new feature. You could get the funds in the account in a lump sum when you left. If you left early you got the money in the account. If you left at retirement age you got the money that was needed to produce the benefit you were promised. Which was based on current interest rates. The second company had a plan where they published the funding formula. You knew with every quarterly statement how much was in your account, and what interest it had earned, and what benefit they estimated you would receive if you stayed until retirement age. This fund felt almost like a defined contribution, because the formula was published. If most people took the lump sum that was the only part that mattered. Both pension plans had a different set of formulas based on marriage status and survivor rules. The interest rates are important because they are used to determine how much money is needed to produce the promised monthly benefit. They are also used to determine how much they need to allocate each year to cover their obligations. If you can't make the math work you need to keep contacting HR. You need to understand how much should be flowing into the account each month.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"232700\",\n \"text\": \"\\\"Firstly, you should familiarise yourself with your options for your pension fund. They changed as of 6th April 2015 so it's all quite new. The Government's guidance on it is here. If you haven't already taken a tax-free lump sum from your pension fund, you can take up to 25% totally tax free immediately. That makes getting a house for 40K very accessible. Beyond the 25%, you can take any of it out whenever you want (\\\"\\\"flexi-access drawdown\\\"\\\" or \\\"\\\"lump sum payment\\\"\\\", depending on whether you take the 25% out up front or not). That'll be taxed, as if you earned it as income. So if you didn't have any other income, you can take another £10600 without tax this tax year, and then another £10600 or whatever the allowance goes up to next tax year, and so on. Above that you'd have to pay 20% tax until you reach the higher-rate tax threshold at about £40K/year. You say you do have other income so you'll have to take that into account as well when calculating what tax you'd have to pay. If you've reached state pension age that will add some more income, of course. Or, as you suggest, you can buy an annuity. You can do that with some or all of the money, and you can still take the 25% tax-free first. If you do buy an annuity the income from it will all be taxed, but again your personal allowance will apply. Essentially an annuity is the least risky option, particularly if you get one that is uprated with inflation. Uprating with inflation makes the initial income even lower but protects you against cost of living rises as you get older. In exchange for avoiding that risk, you probably lose out on average compared to some more risky options. You might choose to get an annuity large enough to cover your basic needs and take more chances with the rest.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"325185\",\n \"text\": \"We can't know the future, of course, but we know that on average it's better to invest a lump sum. We can look at some periods of recent history to get a sense of the difference between a lump sum 450k investment and maybe say 5 years of 90k. Using S&P 500 return rates, let's say you started investing on Jan 1, 2008: Here, spreading your investing over 5 years earns you an extra $163k. Starting a year later, the same strategy would earn you $327k less than a lump investment: I looked at some other periods, but the story doesn't change from what we already knew; you can reduce risk of losing a big chunk due to a bad year, but it comes at the cost of potential gains. Perhaps you could make a killing by waiting for the next down-turn and buying on the cheap, or maybe you'll just be wasting time and money as the market enjoys sustained growth. I'd go with a lump, trusting the averages; but you're right, another 2008 with no recovery would suck. As for holding $50k back it depends primarily on your monthly budget, many people suggest a 3-8 month liquid emergency fund, I like 6 months. Go with what you're comfortable with.\",\n \"title\": \"\"\n }\n]"}}},{"rowIdx":167,"cells":{"query_id":{"kind":"string","value":"5a891a6f55429951533612c3"},"query":{"kind":"string","value":"What other film, beside the American neo-noir dystopian science fiction action film directed by Alex Proyas was considered a blockbuster in 2004?"},"positive_passages":{"kind":"list like","value":[{"docid":"294634","text":"The year 2004 in film involved some significant events. Major releases of sequels took place. It included blockbuster films like \"Shrek 2\", \"Harry Potter and the Prisoner of Azkaban\", \"The Bourne Supremacy\", \"Van Helsing\", \"The Passion of the Christ\", \"\", \"Thunderbirds\", \"Meet the Fockers\", \"Harold and Kumar\", \"The Day After Tomorrow\", \"Anchorman\", \"Saw\", \"\", \"Spider-Man 2\", \"Alien vs. Predator\", \"The Incredibles\", \"Kill Bill Vol. 2\", \"Fahrenheit 9/11\", \"I, Robot\", \"Ocean's Twelve\" and \"\".","title":""},{"docid":"564947","text":"I, Robot (stylized as i,robot ) is a 2004 American neo-noir dystopian science fiction action film directed by Alex Proyas. The screenplay by Jeff Vintar and Akiva Goldsman is from a screen story by Vintar, suggested by Isaac Asimov's short-story collection of the same name. The film stars Will Smith, Bridget Moynahan, Bruce Greenwood, James Cromwell, Chi McBride, Alan Tudyk and Shia LaBeouf.","title":""}],"string":"[\n {\n \"docid\": \"294634\",\n \"text\": \"The year 2004 in film involved some significant events. Major releases of sequels took place. It included blockbuster films like \\\"Shrek 2\\\", \\\"Harry Potter and the Prisoner of Azkaban\\\", \\\"The Bourne Supremacy\\\", \\\"Van Helsing\\\", \\\"The Passion of the Christ\\\", \\\"\\\", \\\"Thunderbirds\\\", \\\"Meet the Fockers\\\", \\\"Harold and Kumar\\\", \\\"The Day After Tomorrow\\\", \\\"Anchorman\\\", \\\"Saw\\\", \\\"\\\", \\\"Spider-Man 2\\\", \\\"Alien vs. Predator\\\", \\\"The Incredibles\\\", \\\"Kill Bill Vol. 2\\\", \\\"Fahrenheit 9/11\\\", \\\"I, Robot\\\", \\\"Ocean's Twelve\\\" and \\\"\\\".\",\n \"title\": \"\"\n },\n {\n \"docid\": \"564947\",\n \"text\": \"I, Robot (stylized as i,robot ) is a 2004 American neo-noir dystopian science fiction action film directed by Alex Proyas. The screenplay by Jeff Vintar and Akiva Goldsman is from a screen story by Vintar, suggested by Isaac Asimov's short-story collection of the same name. The film stars Will Smith, Bridget Moynahan, Bruce Greenwood, James Cromwell, Chi McBride, Alan Tudyk and Shia LaBeouf.\",\n \"title\": \"\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"1884712","text":"Dark City is a 1998 American-Australian neo-noir science fiction film directed by Alex Proyas. The screenplay was written by Proyas, Lem Dobbs and David S. Goyer. The film stars Rufus Sewell, Kiefer Sutherland, Jennifer Connelly, and William Hurt. Sewell plays John Murdoch, an amnesiac man who finds himself suspected of murder. Murdoch attempts to discover his true identity and clear his name while on the run from the police and a mysterious group known only as the \"Strangers\".","title":""},{"docid":"574909","text":"Alien Nation is a 1988 American buddy cop neo-noir science fiction action film directed by Graham Baker. The ensemble cast features James Caan, Mandy Patinkin and Terence Stamp. The film depicts the assimilation of the \"Newcomers\", an alien race settling in Los Angeles, much to the initial dismay of the local population. The plot integrates the neo-noir and buddy cop film genres with a science fiction theme, centering on a union between a veteran police investigator (Caan) and an extraterrestrial (Patinkin); the first Newcomer detective. The duo probe a criminal underworld attempting to solve a homicide.","title":""},{"docid":"25493","text":"Sir Ridley Scott (born 30 November 1937) is an English film director and producer. Following his commercial breakthrough with the science-fiction horror film \"Alien\" (1979), his best known works include the neo-noir dystopian science fiction film \"Blade Runner\" (1982), historical drama and Best Picture Oscar winner \"Gladiator\" (2000), and science fiction film \"The Martian\" (2015).","title":""},{"docid":"314444","text":"Alexander \"Alex\" Proyas ( ; born 23 September 1963) is an Australian film director, screenwriter, and producer. Proyas is best known for directing the films \"The Crow\" (1994), \"Dark City\" (1998), \"I, Robot\" (2004), \"Knowing\" (2009), and \"Gods of Egypt\" (2016).","title":""},{"docid":"44059","text":"Harrison Ford (born July 13, 1942) is an American actor and film producer. He gained worldwide fame for his starring roles as Han Solo in the \"Star Wars\" film series and as the title character of the \"Indiana Jones\" film series. Ford is also known for his roles as Rick Deckard in the neo-noir dystopian science fiction film \"Blade Runner\" (1982); John Book in the thriller \"Witness\" (1985), for which he was nominated for the Academy Award for Best Actor; and Jack Ryan in the action films \"Patriot Games\" (1992) and \"Clear and Present Danger\" (1994).","title":""},{"docid":"234537","text":"Equilibrium is a 2002 American dystopian science fiction action film written and directed by Kurt Wimmer and starring Christian Bale, Emily Watson, and Taye Diggs.","title":""},{"docid":"5869916","text":"Omega Doom is a 1996 American science-fiction action film directed by Albert Pyun and starring Rutger Hauer. It was written by Pyun and Ed Naha. The story, set in a dystopian future, concerns a robot warrior who, during a nuclear winter, plays both sides of a robot civil war in a small town. The film is mostly based on \"Yojimbo\" by Akira Kurosawa, and it was the third movie in Pyun's \"Cyborg Trilogy\". It is considered a cult film.","title":""},{"docid":"8960083","text":"Megaville is an independent/low-budget direct-to-video 1990 American science fiction film, starring Billy Zane in his first lead role. \"Megaville\" is a neo-noir psychological thriller which utilizes elements of science fiction such as cyberpunk and existentialism.","title":""},{"docid":"47404924","text":"What Happened to Monday (known as Seven Sisters in France) is a dystopian science fiction thriller film, written by Max Botkin and Kerry Williamson, directed by Tommy Wirkola and starring Noomi Rapace, Glenn Close, and Willem Dafoe. Netflix bought the streaming rights to the film for the United States and other markets. Netflix released the film on August 18, 2017.","title":""},{"docid":"17544255","text":"Knowing (stylized as KNOW1NG) is a 2009 science fiction thriller film directed by Alex Proyas and starring Nicolas Cage. The project was originally attached to a number of directors under Columbia Pictures, but it was placed in turnaround and eventually picked up by Escape Artists. Production was financially backed by Summit Entertainment. \"Knowing\" was filmed in Docklands Studios Melbourne, Australia, using various locations to represent the film's Boston-area setting.","title":""},{"docid":"469019","text":"Thunderbirds is a 2004 British-American-French science fiction action-adventure film based on the 1960s television series of the same name, directed by Jonathan Frakes. The film, written by William Osborne and Michael McCullers, was released on 24 July 2004 in the United Kingdom and 30 July 2004 in the United States, with later opening dates in other countries. Whereas the original TV series used a form of puppetry termed \"Supermarionation\", the film's characters are portrayed by live-action actors.","title":""},{"docid":"6944155","text":"Mark Robert Michael Wahlberg (born June 5, 1971) is an American actor, producer, businessman, former model, and former rapper. Wahlberg was known as Marky Mark in his early career as frontman for the group Marky Mark and the Funky Bunch, releasing the albums \"Music for the People\" and \"You Gotta Believe\". Wahlberg later transitioned to acting, appearing in films such as the drama \"Boogie Nights\" and the satirical war comedy-drama \"Three Kings\" during the 1990s. In the 2000s, he starred in the biographical disaster drama \"The Perfect Storm\", the science fiction film \"Planet of the Apes\", the heist film \"The Italian Job\", and the Martin Scorsese-directed neo-noir crime drama \"The Departed\", for which he received an Academy Award nomination for Best Supporting Actor. In the 2010s, he starred in the action comedy \"The Other Guys\" alongside Will Ferrell, the biographical sports drama \"The Fighter\" (for which he earned an Academy Award nomination as a producer for Best Picture), the comedy \"Ted\", the war film \"Lone Survivor\", the crime comedy \"Pain & Gain\", the science fiction action film \"\" and the sequel \"\", the comedy \"Daddy's Home\", the disaster film \"Deepwater Horizon\", and the thriller \"Patriots Day\".","title":""},{"docid":"406339","text":"The Crow is a 1994 American dark fantasy action film directed by Alex Proyas, written by David J. Schow and John Shirley. The film stars Brandon Lee in his final film appearance. The film is based on James O'Barr's 1989 comic book \"The Crow\", and tells the story of Eric Draven (Lee), a rock musician who is revived from the dead to avenge his own death as well as the rape and murder of his fiancée.","title":""},{"docid":"26054678","text":"Virtual Revolution is a 2016 indie science fiction film directed and written by Guy-Roger Duvert, and starring Mike Dopud, Jane Badler, Jochen Hägele and Maximilien Poullein.The film is set in dystopian Neo Paris in which people have embraced virtual reality completely.","title":""},{"docid":"2983487","text":"Ultraviolet is a 2006 American dystopian science fiction action thriller film written and directed by Kurt Wimmer and produced by Screen Gems. It stars Milla Jovovich as Violet Song, Cameron Bright as Six, and Nick Chinlund as Ferdinand Daxus. It was released in North America on March 3, 2006. The film was released on DVD and Blu-ray Disc on June 27, 2006.","title":""},{"docid":"30007","text":"The Matrix is a 1999 science fiction action film written and directed by The Wachowskis, starring Keanu Reeves, Laurence Fishburne, Carrie-Anne Moss, Hugo Weaving, and Joe Pantoliano. It depicts a dystopian future in which reality as perceived by most humans is actually a simulated reality called \"the Matrix\", created by sentient machines to subdue the human population, while their bodies' heat and electrical activity are used as an energy source. Computer programmer Neo learns this truth and is drawn into a rebellion against the machines, which involves other people who have been freed from the \"dream world.\"","title":""},{"docid":"4327099","text":"Blade Runner is a 1982 American neo-noir science fiction film directed by Ridley Scott, and starring Harrison Ford, Rutger Hauer, Sean Young, and Edward James Olmos. The film, written by Hampton Fancher and David Peoples, is an adaptation of the 1968 novel \"Do Androids Dream of Electric Sheep?\" by Philip K. Dick.","title":""},{"docid":"44569317","text":"The Maze Runner film series consists of science-fiction dystopian action adventure films based on \"The Maze Runner\" novels by the American author James Dashner. Produced by Ellen Goldsmith-Vein and distributed by 20th Century Fox, the films star Dylan O'Brien, Kaya Scodelario, Thomas Brodie-Sangster, Ki Hong Lee, Dexter Darden and Patricia Clarkson. Wes Ball directed all three films.","title":""},{"docid":"826409","text":"Collateral is a 2004 American neo-noir crime action thriller directed by Michael Mann and written by Stuart Beattie. It stars Tom Cruise cast against type as a contract killer and Jamie Foxx as a taxi driver who becomes Cruise's hostage during an evening of the hitman's work. The film also features Jada Pinkett Smith and Mark Ruffalo.","title":""},{"docid":"27383563","text":"Looper is a 2012 American neo-noir science fiction thriller film written and directed by Rian Johnson, and produced by Ram Bergman and James D. Stern. It stars Bruce Willis, Joseph Gordon-Levitt, and Emily Blunt. It revolves around criminal syndicates using contracted killers called \"loopers\" to kill victims sent through time travel.","title":""},{"docid":"826026","text":"Noir is a science fiction novel by K. W. Jeter, published in 1998. It uses the conventions of film noir – the alienated, doomed hero, the cynical private detective, the femme fatale, universal corruption and moral breakdown – to portray a dystopian vision of capitalism run riot.","title":""},{"docid":"46788290","text":"Maze Runner: The Death Cure (also known simply as The Death Cure) is an upcoming American dystopian science-fiction action thriller film directed by Wes Ball, based on \"The Death Cure\", the final book in \"The Maze Runner\" trilogy, written by James Dashner, with a screenplay by T.S. Nowlin. It is the sequel to the 2015 film \"\" and the third and final installment in the \"Maze Runner\" film series.","title":""},{"docid":"29446866","text":"In Time is a 2011 American dystopian science fiction action thriller film written, directed, and produced by Andrew Niccol and starring Justin Timberlake, Amanda Seyfried and Cillian Murphy that takes place in a society where people stop aging at 25 and each has a clock on their arm that counts down how long they have to live. The film was released on October 28, 2011.","title":""},{"docid":"8776448","text":"A Dirty Carnival (; lit: or=4 weeks. RESULTS: Mean LDL-C concentration at the end of each phase (+/- SD) was 161 +/- 20, 161 +/- 26 and 170 +/- 24 mg/dL for the whole bean soy milk, the soy protein isolate milk, and the dairy milk, respectively (p = 0.9 between soy milks, p = 0.02 for each soy milk vs. dairy milk). No significant differences by type of milk were observed for HDL-cholesterol, triacylglycerols, insulin, or glucose. CONCLUSION: A 25 g dose of daily soy protein from soy milk led to a modest 5% lowering of LDL-C relative to dairy milk among adults with elevated LDL-C. The effect did not differ by type of soy milk and neither soy milk significantly affected other lipid variables, insulin or glucose.","title":"Effect of two types of soy milk and dairy milk on plasma lipids in hypercholesterolemic adults: a randomized trial."},{"docid":"MED-5013","text":"INTRODUCTION: Endothelial dysfunction is known to occur in patients with coronary artery disease. Flow-mediated dilation of the brachial artery using Doppler ultrasound is a non-invasive technique for the assessment of endothelial function. The objective of the study was to use the above method to evaluate the pathophysiology of high-fat (HF) intake on endothelial function in a local population. A popular local dish \"nasi-lemak\", a source of high saturated fat content from coconut milk, was chosen to represent a local high-fat meal (LHF). In addition, the effects of a Western high-fat (WHF) (\"McDonald's\") meal and a low-fat (LF) meal control on endothelial function were studied. MATERIALS AND METHODS: The study population consisted of 10 healthy male non-smoker (mean age 22 +/- 2 years) with normal body mass index, normal fasting sugar and lipid profiles. Nitric oxide dependent flow-mediated dilation and nitric oxide independent (GTN) dilation was assessed by Doppler flow in the brachial artery before and 4 hours after each meal on separate occasions by 2 experienced sonographers blinded to the type of meals. RESULTS: The baseline brachial artery size, baseline vessel flow and increase in flow after cuff deflation were similar for each of the six arterial studies. In response to reactive hyperaemia after cuff deflation, the endothelium-dependent dilation was significantly different between the meals. There was a marked decrease in endothelium-dependent dilation after the WHF meal compared to the LF meal (8.6 +/- 2.2% vs. -0.8 +/- 1.1%, P < 0.006). There was also a marked decrease in endothelium-dependent dilation after the LHF meal compared to the LF meal (7.7 +/- 2.1% vs. -0.8 +/- 1.1%, P < 0.001). When comparing between the two HF meals, the change in endothelium-dependent dilation was not significant (7.7 vs. 8.6%, P = 0.678). GTN-induced dilation was not significantly different before and after the LF, WHF or LHF (0.1 +/- 0.5% vs. 0.2 +/- 0.9% vs. 1.3 +/- 0.5%, P = 0.094). CONCLUSION: The results suggest that in a local population, impairment of endothelial function is a possible mechanism in the pathophysiology of atherosclerosis from HF intake, beyond just affecting lipid levels. This effect is observed after both a LHF and a WHF meal intake. This technique to study endothelial function may be a useful non-invasive screening tool in the study of other HF diet choices and provides further information for the education of the influence of dietary choices on atherosclerosis.","title":"Impairment of endothelial function--a possible mechanism for atherosclerosis of a high-fat meal intake."},{"docid":"MED-1968","text":"Our aim was to determine the effects of increasing amounts of dietary cholesterol (0-710 mg) on the postprandial plasma lipid responses and lipoprotein changes in normolipidemic human subjects. Ten subjects were fed five different test meals in a random order: one meal did not contain fat or cholesterol while the four others contained a fixed amount of lipids (45 g) and 0, 140, 280, and 710 mg cholesterol, respectively. Fasting and post-meal blood samples were obtained for 7 h. Large and small triglyceride-rich lipoproteins (TRL), low density (LDL), and high density (HDL) lipoproteins were isolated. Compared to the no-fat, no-cholesterol meal, the fat-enriched meals raised (P < 0.05) plasma triglycerides, phospholipids, and free cholesterol and lowered cholesteryl esters postprandially. The meals containing zero or 140 mg cholesterol generally elicited comparable postprandial plasma and lipoprotein lipid responses. The meals providing 280 or 710 mg cholesterol significantly increased postprandial plasma phospholipids and large TRL triglycerides and decreased plasma esterified cholesterol. The lipid composition of the large TRLs and the concentrations of the small TRL lipid components were not altered postprandially by cholesterol intake. On the other hand, LDL free cholesterol increased after 3 h, LDL cholesteryl esters dropped after 3 and 7 h, HDL cholesteryl esters dropped after 3 h, and HDL phospholipids increased 7 h after ingesting meals highly enriched in cholesterol. Blood insulin, apoA-I and apoB were not altered postprandially by cholesterol intake. Thus, the data show that ingesting more than 140 mg cholesterol per meal significantly alters the postprandial lipoprotein response in healthy subjects.","title":"Effects of increasing amounts of dietary cholesterol on postprandial lipemia and lipoproteins in human subjects."},{"docid":"MED-2253","text":"Twenty three adults ingested 203Pb as lead acetate on the 12th hour of a 19 h fast. Retention measured 7 days later in a whole-body counter was 61% and whole-body turnover rates suggested that initial uptake had been considerably greater. Balanced meals eaten with 203Pb reduced lead uptake to 4% and the influence of the food lasted for up to 3 h. The effects of phytate, ethylene-diaminetetra acetate (EDTA), caffeine, alcohol, glucose, a liquid meal and a light snack were tested separately with intermediate results. The effect of a meal was probably largely due to its content of calcium and phosphate salts but lead uptake was probably further reduced by phytate which is plentiful in whole cereals and it was probably increased by a factor in milk. Uptake with skimmed milk was the same as with whole milk and we suggested that the factor was not fat. Comestibles with low mineral and phytate contents reduced lead uptake by intermediate amounts, possibly by stimulation of digestive secretions. The avid uptake of lead during a fast, the large reduction of lead uptake with meals and the likelihood of variations in gastric-emptying rates and dietary habits may be major causes of variation in body burdens of lead in the population.","title":"Effects of meals and meal times on uptake of lead from the gastrointestinal tract in humans."},{"docid":"MED-5271","text":"OBJECTIVES: This study investigated the postprandial effect of components of the Mediterranean diet on endothelial function, which may be an atherogenic factor. BACKGROUND: The Mediterranean diet, containing olive oil, pasta, fruits, vegetables, fish, and wine, is associated with an unexpectedly low rate of cardiovascular events. The Lyon Diet Heart Study found that a Mediterranean diet, which substituted omega-3-fatty-acid-enriched canola oil for the traditionally consumed omega-9 fatty-acid-rich olive oil, reduced cardiovascular events. METHODS: We fed 10 healthy, normolipidemic subjects five meals containing 900 kcal and 50 g fat. Three meals contained different fat sources: olive oil, canola oil, and salmon. Two olive oil meals also contained antioxidant vitamins (C and E) or foods (balsamic vinegar and salad). We measured serum lipoproteins and glucose and brachial artery flow-mediated vasodilation (FMD), an index of endothelial function, before and 3 h after each meal. RESULTS: All five meals significantly raised serum triglycerides, but did not change other lipoproteins or glucose 3 h postprandially. The olive oil meal reduced FMD 31% (14.3 +/- 4.2% to 9.9 +/- 4.5%, p = 0.008). An inverse correlation was observed between postprandial changes in serum triglycerides and FMD (r = -0.47, p < 0.05). The remaining four meals did not significantly reduce FMD. CONCLUSIONS: In terms of their postprandial effect on endothelial function, the beneficial components of the Mediterranean and Lyon Diet Heart Study diets appear to be antioxidant-rich foods, including vegetables, fruits, and their derivatives such as vinegar, and omega-3-rich fish and canola oils.","title":"The postprandial effect of components of the Mediterranean diet on endothelial function."},{"docid":"MED-4318","text":"Preliminary data in the literature indicate that iron absorption from a meal may be increased when consumed with low-pH beverages such as cola, and it is also possible that sugar iron complexes may alter iron availability. A randomized, crossover trial was conducted to compare the bioavailability of nonheme iron from a vegetarian pizza meal when consumed with 3 different beverages (cola, diet cola, and mineral water). Sixteen women with serum ferritin concentrations of 11-54 µg/L were recruited and completed the study. The pizza meal contained native iron and added ferric chloride solution as a stable isotope extrinsic label; the total iron content of the meal was ~5.3 mg. Incorporation of iron from the meal into RBC was not affected by the type of drink (9.9% with cola, 9.4% with diet cola, and 9.6% with water). Serum ferritin and plasma hepcidin were correlated (r = 0.66; P<0.001) and both were significant predictors of iron bioavailability, but their combined effect explained only 30% of the inter-individual variation (P<0.001) and illustrates the current lack of understanding of mechanisms responsible for the fine-tuning of iron absorption. Although there was no effect of low-pH drinks on iron bioavailability in healthy women, their effect on absorption of fortification iron that requires solubilization in dilute acid, such as reduced iron, and in individuals with low gastric acid production, such as older people and individuals with Helicobacter pylori infection, warrants further investigation.","title":"Low-pH cola beverages do not affect women's iron absorption from a vegetarian meal."},{"docid":"MED-760","text":"There is much interest in the potential of dietary antioxidants to attenuate in vivo oxidative stress, but little characterization of the time course of plasma effects exists. Culinary spices have demonstrated potent in vitro antioxidant properties. The objective of this study was to examine whether adding 14 g of a high antioxidant spice blend to a 5060-kJ (1200 kcal) meal exerted significant postprandial effects on markers of plasma antioxidant status and metabolism. Healthy overweight men (n = 6) consumed a control and spiced meal in a randomized crossover design with 1 wk between testing sessions. Blood was sampled prior to the meal and at 30-min intervals for 3.5 h (total of 8 samples). Mixed linear models demonstrated a treatment × time interaction (P < 0.05) for insulin and TG, corresponding with 21 and 31% reductions in postprandial levels with the spiced meal, respectively. Adding spices to the meal significantly increased the ferric reducing antioxidant power, such that postprandial increases following the spiced meal were 2-fold greater than after the control meal (P = 0.009). The hydrophilic oxygen radical absorbance capacity (ORAC) of plasma also was increased by spices (P = 0.02). There were no treatment differences in glucose, total thiols, lipophilic ORAC, or total ORAC. The incorporation of spices into the diet may help normalize postprandial insulin and TG and enhance antioxidant defenses.","title":"A High Antioxidant Spice Blend Attenuates Postprandial Insulin and Triglyceride Responses and Increases Some Plasma Measures of Antioxidant Activity in Healthy, Overweight Men"}],"string":"[\n {\n \"docid\": \"MED-2140\",\n \"text\": \"Background Around the world, beans and rice are commonly consumed together as a meal. With type 2 diabetes increasing, the effect of this traditional diet pattern on glycemic response has not been studied fully. Methods We evaluated the glycemic response of bean and rice traditional meals compared to rice alone in adults with type 2 diabetes. Seventeen men and women with type 2 diabetes controlled by metformin (n = 14) or diet/exercise (n = 3) aged 35–70 years participated in the randomized 4 × 4 crossover trial. The white long grain rice control, pinto beans/rice, black beans/rice, red kidney beans/rice test meals, matched for 50 grams of available carbohydrate, were consumed at breakfast after a 12 hour fast. Capillary blood glucose concentrations at baseline and at 30 minute intervals up to 180 minutes postprandial were collected. MANOVA for repeated measures established glucose differences between treatments. Paired t tests identified differences between bean types and the rice control following a significant MANOVA. Results Postprandial net glucose values were significantly lower for the three bean/rice treatments in contrast to the rice control at 90, 120 and 150 minutes. Incremental area under the curve values were significantly lower for the pinto and black bean/rice meals compared to rice alone, but not for kidney beans. Conclusions Pinto, dark red kidney and black beans with rice attenuate the glycemic response compared to rice alone. Promotion of traditional foods may provide non-pharmaceutical management of type 2 diabetes and improve dietary adherence with cultural groups. Trial registration Clinical Trials number NCT01241253\",\n \"title\": \"Bean and rice meals reduce postprandial glycemic response in adults with type 2 diabetes: a cross-over study\"\n },\n {\n \"docid\": \"MED-1612\",\n \"text\": \"Type II diabetic subjects were given 50 g protein, 50 g glucose, or 50 g glucose with 50 g protein as a single meal in random sequence. The plasma glucose and insulin response was determined over the subsequent 5 h. The plasma glucose area above the baseline following a glucose meal was reduced 34% when protein was given with the glucose. When protein was given alone, the glucose concentration remained stable for 2 h and then declined. The insulin area following glucose was only modestly greater than with a protein meal (97 +/- 35, 83 +/- 19 microU X h/ml, respectively). When glucose was given with protein, the mean insulin area was considerably greater than when glucose or protein was given alone (247 +/- 33 microU X h/ml). When various amounts of protein were given with 50 g glucose, the insulin area response was essentially first order. Subsequently, subjects were given 50 g glucose or 50 g glucose with 50 g protein as two meals 4 h apart in random sequence. The insulin areas were not significantly different for each meal but were higher when protein + glucose was given. After the second glucose meal the plasma glucose area was 33% less than after the first meal. Following the second glucose + protein meal the plasma glucose area was markedly reduced, being only 7% as large as after the first meal. These data indicate that protein given with glucose will increase insulin secretion and reduce the plasma glucose rise in at least some type II diabetic persons.\",\n \"title\": \"Effect of protein ingestion on the glucose and insulin response to a standardized oral glucose load.\"\n },\n {\n \"docid\": \"MED-3136\",\n \"text\": \"The objective of this study was to determine the influence of frequent and long-term consumption of legume seeds on colonic function. Two groups of subjects were studied--one group habitually consumed legume seeds as part of their normal diet, a second group only infrequently consumed legumes. No differences between these groups could be detected for fecal output and frequency, intestinal transit time, VFA excretion or fecal pH during 23-day study periods in which subjects consumed either their usual diet or 100 g red kidney beans, daily. However, the addition of beans to the diets of both groups provided significantly more dietary fiber, and produced greater fecal output and a higher concentration of VFA in feces. Fecal output appeared to be determined by two independent parameters--dietary fiber intake and VFA excretion. Beans provided a physiologically useful source of dietary fiber and favorably influenced colonic function.\",\n \"title\": \"Influence of frequent and long-term bean consumption on colonic function and fermentation.\"\n },\n {\n \"docid\": \"MED-2970\",\n \"text\": \"There is increasing evidence that the postprandial state is an important contributing factor to chronic disease. The role of fruit phenolic compounds to protect health and lower disease risk through their actions in mitigating fed-state metabolic and oxidative stressors is of interest and the topic of the present paper. Two main questions are posed: first, what is the role of plant foods, specifically fruits rich in complex and simple phenolic compounds in postprandial metabolic management; and second, does the evidence support consuming these fruits with meals as a practical strategy to preserve health and lower risk for disease? This review provides an overview of the postprandial literature, specifically on the effect of fruits and their inherent phenolic compounds in human subjects on postprandial lipaemia, glycaemia/insulinaemia and associated events, such as oxidative stress and inflammation. Among the identified well-controlled human trials using a postprandial paradigm, >50 % of the trials used wine or wine components and the remaining used various berries. Notwithstanding the need for more research, the collected data suggest that consuming phenolic-rich fruits increases the antioxidant capacity of the blood, and when they are consumed with high fat and carbohydrate 'pro-oxidant and pro-inflammatory' meals, they may counterbalance their negative effects. Given the content and availability of fat and carbohydrate in the Western diet, regular consumption of phenolic-rich foods, particularly in conjunction with meals, appears to be a prudent strategy to maintain oxidative balance and health.\",\n \"title\": \"Postprandial metabolic events and fruit-derived phenolics: a review of the science.\"\n },\n {\n \"docid\": \"MED-5260\",\n \"text\": \"OBJECTIVES: The goal of this study was to evaluate the effects of the phenolic content of virgin olive oil on endothelial reactivity. BACKGROUND: Endothelial-dependent vasodilatation is impaired during the postprandial state, and oxidative stress could play a key role in its development. METHODS: Twenty-one hypercholesterolemic volunteers received two breakfasts, using a randomized sequential crossover design. Both arms received the same olive oil, but one had its phenolic acid content reduced from 400 to 80 ppm. Ischemic reactive hyperemia (IRH) was measured with a laser-Doppler procedure at baseline and 2 h and 4 h after oil intake. Postprandial plasma concentrations of lipid fractions, lipoperoxides (LPO), 8-epi prostaglandin-F(2alpha), and nitrates/nitrites (NO(x)) were obtained at baseline and after 2 h of the fat meal. RESULTS: The intake of the polyphenol-rich breakfast was associated with an improvement in endothelial function, as well as a greater increase in concentrations of NO(x) (p < 0.001) and a lower increase in LPO (p < 0.005) and 8-epi prostaglandin-F2alpha (p < 0.001) than the ones induced by the low polyphenol fat meal. A positive correlation was found to exist between NO(x) and enhanced endothelial function at the second hour (r = 0.669; p < 0.01). Furthermore, a negative correlation was found between IRH and LPO (r = -0.203; p < 0.05) and 8-epi prostaglandin-F2alpha levels (r = -0.440; p < 0.05). CONCLUSIONS: A meal containing high-phenolic virgin olive oil improves ischemic reactive hyperemia during the postprandial state. This phenomenon might be mediated via reduction in oxidative stress and the increase of nitric oxide metabolites.\",\n \"title\": \"Phenolic content of virgin olive oil improves ischemic reactive hyperemia in hypercholesterolemic patients.\"\n },\n {\n \"docid\": \"MED-1671\",\n \"text\": \"BACKGROUND: Sucrose induces high postprandial glucose and insulin responses. In vitro studies suggest that berries may reduce the digestion and absorption of sucrose and thereby suppress postprandial glycemia, but the evidence in humans is limited. OBJECTIVE: We investigated the effects of sucrose ingested with blackcurrants (Ribes nigrum) and lingonberries (Vaccinium vitis-idaea) on postprandial glucose, insulin, and free fatty acid responses. DESIGN: Twenty healthy women participated in a randomized, controlled, crossover meal study. They consumed whole blackcurrants or lingonberries (150 g served as purées) or blackcurrant or lingonberry nectars (300 mL), each with 35 g added sucrose. Sucrose alone (35 g in 300 mL water) was used as a reference. Blood samples were collected at 0, 15, 30, 45, 60, 90, and 120 min. RESULTS: In comparison with sucrose alone, ingestion of sucrose with whole berries resulted in reduced glucose and insulin concentrations during the first 30 min and a slower decline during the second hour and a significantly improved glycemic profile. Berries prevented the sucrose-induced late postprandial hypoglycemic response and the compensatory free fatty acid rebound. Nearly similar effects were observed when sucrose was consumed with berry nectars. The improved responses were evident despite the higher content of available carbohydrate in the berry and nectar meals, because of the natural sugars present in berries. CONCLUSIONS: Blackcurrants and lingonberries, as either whole berries or nectars, optimize the postprandial metabolic responses to sucrose. The responses are consistent with delayed digestion of sucrose and consequent slower absorption of glucose.\",\n \"title\": \"Postprandial glucose, insulin, and free fatty acid responses to sucrose consumed with blackcurrants and lingonberries in healthy women.\"\n },\n {\n \"docid\": \"MED-1880\",\n \"text\": \"Legumes are the basés diet in several countries. They hold a high nutritional value, but other properties related to human health are nowadays being studied. The aim of this work was to study the influence of processes (boiling or germination) on the phenolic composition of dark beans (Phaseolus vulgaris L. c.v. Tolosana) and their effect on their antioxidant, neuroprotective and anticancer ability. Phenolic composition of raw and processed dark beans was analysed by HPLC-PAD and HPLC-ESI/MS. The antioxidant activity was evaluated by ORAC. Astrocytes cultures (U-373) have been used to test their neuroprotective effect. Anticancer activities were evaluated on three different cell lines (renal adenocarcinoma (TK-10), breast adenocarcinoma (MCF-7) and melanoma (UACC-62)) by sulphorhodamine B method. Qualitative and quantitative differences in phenolic composition have been observed between raw and processed dark beans that influence the antioxidant activity, mainly for germinated samples which show a decrease of antioxidant capacity. Although every assayed extracts decreased reactive oxygen species release and exhibited cytotoxicity activities on cancer cell lines, raw beans proved to be the most active in neuroprotective and antitumoral effects; this sample is especially rich in phenolic compounds, mainly anthocyanins. This study further demonstrated that phenolic composition of dark beans is related with cooking process and so with their neuroprotective and anticancer activity; cooking of dark beans improves their digestion and absorption at intestinal level, while maintaining its protective ability on oxidative process at cellular level. Copyright © 2012 Elsevier Ltd. All rights reserved.\",\n \"title\": \"Effect of cooking and germination on phenolic composition and biological properties of dark beans (Phaseolus vulgaris L.).\"\n },\n {\n \"docid\": \"MED-5079\",\n \"text\": \"OBJECTIVE: To determine effects of daily intake of 1/2 cup pinto beans, black-eyed peas or carrots (placebo) on risk factors for coronary heart disease (CHD) and diabetes mellitus (DM) in free-living, mildly insulin resistant adults over an 8 week period. METHODS: Randomized, crossover 3x3 block design. Sixteen participants (7 men, 9 women) received each treatment for eight-weeks with two-week washouts. Fasting blood samples collected at beginning and end of periods were analyzed for total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol, triacylglycerols, high-sensitivity C-reactive protein, insulin, glucose, and hemoglobin A1c. RESULTS: A significant treatment-by-time effect impacted serum TC (p = 0.026) and LDL (p = 0.033) after eight weeks. Paired t-tests indicated that pinto beans were responsible for this effect (p = 0.003; p = 0.008). Mean change of serum TC for pinto bean, black-eyed pea and placebo were -19 +/- 5, 2.5 +/- 6, and 1 +/- 5 mg/dL, respectively (p = 0.011). Mean change of serum LDL-C for pinto bean, black-eyed pea and placebo were -14 +/- 4, 4 +/- 5, and 1 +/- 4 mg/dL, in that order (p = 0.013). Pinto beans differed significantly from placebo (p = 0.021). No significant differences were seen with other blood concentrations across the 3 treatment periods. CONCLUSIONS: Pinto bean intake should be encouraged to lower serum TC and LDL-C, thereby reducing risk for CHD.\",\n \"title\": \"Pinto bean consumption reduces biomarkers for heart disease risk.\"\n },\n {\n \"docid\": \"MED-3138\",\n \"text\": \"Background Many consumers avoid eating beans because they believe legume consumption will cause excessive intestinal gas or flatulence. An increasing body of research and the 2010 Dietary Guidelines for Americans supports the benefits of a plant-based diet, and legumes specifically, in the reduction of chronic disease risks. The purpose of the current research was to investigate the perception of increased flatulence and gastrointestinal discomfort among participants who consumed a ½ cup of beans daily for 8 or 12 weeks. Methods Participants in three studies to test the effects of beans on heart disease biomarkers completed the same weekly questionnaire to assess gastrointestinal discomfort issues such as increased flatulence, stool changes, and bloating. Studies 1 and 2 were randomized crossover trials. Participants consumed ½ cup of pinto beans, black-eyed peas, and canned carrots as control (n = 17) in Study 1 for three randomized 8-week phases. For Study 2, participants ate ½ cup baked beans or canned carrots as control (n = 29) for two randomized 8-week phases. Study 3 was a parallel arm trial with 40 subjects receiving ½ cup pinto beans and 40 consuming a control soup for 12 weeks. Changes in the frequency of perceived flatulence, stool characteristics, and bloating were the primary outcome measures. Chi-square distributions were examined for the presence or absence of symptoms and demographic characteristics to determine differences by gender, age, body mass index (BMI), and bean type. Results Less than 50% reported increased flatulence from eating pinto or baked beans during the first week of each trial, but only 19% had a flatulence increase with black-eyed peas. A small percentage (3-11%) reported increased flatulence across the three studies even on control diets without flatulence-producing components. Conclusions People's concerns about excessive flatulence from eating beans may be exaggerated. Public health nutritionists should address the potential for gastrointestinal discomfort when increasing fiber intake from beans with clients. It is important to recognize there is individual variation in response to different bean types.\",\n \"title\": \"Perceptions of flatulence from bean consumption among adults in 3 feeding studies\"\n },\n {\n \"docid\": \"MED-2570\",\n \"text\": \"The functional properties, including antioxidant and chemopreventative capacities as well as the inhibitory effects on angiotensin-converting enzyme (ACE), α-glucosidase and pancreatic lipase, of three Australian-grown faba bean genotypes (Nura, Rossa and TF(Ic*As)*483/13) were investigated using an array of in vitro assays. Chromatograms of on-line post column derivatisation assay coupled with HPLC revealed the existence of active phenolics (hump) in the coloured genotypes, which was lacking in the white-coloured breeding line, TF(Ic*As)*483/13. Roasting reduced the phenolic content, and diminished antioxidant activity by 10-40 % as measured by the reagent-based assays (diphenylpicrylhydrazyl, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) and oxygen radical absorbance capacity) in all genotypes. Cell culture-based antioxidant activity assay (cellular antioxidant activity) showed an increase of activity in the coloured genotypes after roasting. Faba bean extracts demonstrated cellular protection ability against H₂O₂-induced DNA damage (assessed using RAW264.7 cells), and inhibited the proliferation of all human cancer cell lines (BL13, AGS, Hep G2 and HT-29) evaluated. However, the effect of faba bean extracts on the non-transformed human cells (CCD-18Co) was negligible. Flow cytometric analyses showed that faba bean extracts successfully induced apoptosis of HL-60 (acute promyelocytic leukaemia) cells. The faba bean extracts also exhibited ACE, α-glucosidase and pancreatic lipase inhibitory activities. Overall, extracts from Nura (buff-coloured) and Rossa (red-coloured) were comparable, while TF(Ic*As)*483/13 (white-coloured) contained the lowest phenolic content and exhibited the least antioxidant and enzyme inhibition activities. These results are important to promote the utilisation of faba beans in human diets for various health benefits.\",\n \"title\": \"In vitro investigations of the potential health benefits of Australian-grown faba beans (Vicia faba L.): chemopreventative capacity and inhibitory ...\"\n },\n {\n \"docid\": \"MED-3141\",\n \"text\": \"OBJECTIVE: To evaluate the associations with chronic disease risk and mortality of the consequences of bean-free diets in Taiwanese adults with regard to gender. DESIGN: A sub-sample of the National Health Interview Survey (NHIS) in 2001 agreed to physical examination in the subsequent year. This group then took part in the Taiwanese Survey of Hyperglycaemia, Hyperlipidaemia and Hypertension (TwSHHH) in 2002. SETTING: Individual records were linked to the eventual death files from 2002 to 2008. SUBJECTS: Up to the end of 2008, a total of 2820 men and 2950 women were tracked by death registry over the 6·8 years of follow-up. RESULTS: Among 38,077 person-years, an average follow-up 6·5 years, 225 all-cause deaths were identified. Generalized linear models showed beans to be favourable for metabolic syndrome (other than for fasting glucose) in men; in women, beans were favourable for waist circumference and HbA1c. Cumulative logistic regression models for the effect of a bean-free diet on metabolic syndrome scores according to the Taiwanese-modified National Cholesterol Education Program-Adult Treatment Panel III (NCEP-tw) gave adjusted odds ratios of 1·83 in men and 1·45 in women. Cox regression models for the bean-free diet showed an increased hazard ratio for all-cause mortality among women (1·98, 95% CI 1·03, 3·81) but not men (1·28, 95% CI 0·76, 2·16). CONCLUSIONS: A bean-free diet may play a role in developing the metabolic syndrome in both genders, and is a significant predictor of all-cause mortality in Taiwanese women but not men.\",\n \"title\": \"A bean-free diet increases the risk of all-cause mortality among Taiwanese women: the role of the metabolic syndrome.\"\n },\n {\n \"docid\": \"MED-2144\",\n \"text\": \"Bean pods (Phaseolus vulgaris) are among the most widely used traditional remedies against diabetes mellitus. Historical knowledge is summarized and compared to recent study results. Reports dating from the first half of the 20(th) century as well as recent publications show contradictory results. It seems that Phaseolus preparations should not be considered the first choice in phytopharmaceutical treatment of diabetes or lead structure research. To be effective, fairly high doses of aqueous extracts need to be given. Because of their fiber content and an alpha-amylase inhibitory effect, beans might be more useful as food components in preventing or ameliorating type 2 diabetes.\",\n \"title\": \"Beans and diabetes: Phaseolus vulgaris preparations as antihyperglycemic agents.\"\n },\n {\n \"docid\": \"MED-4991\",\n \"text\": \"BACKGROUND: Epidemiological studies have shown positive findings associated with legume consumption and measures of cardiovascular disease and obesity. However, few observational trials have examined beans as a separate food variable when determining associations with health parameters. OBJECTIVE: To determine the association of consuming beans on nutrient intakes and physiological parameters using the National Health and Examination Survey (NHANES) 1999-2002. METHODS: Using data from NHANES 1999-2002, a secondary analysis was completed with a reliable 24-hour dietary recall where three groups of bean consumers were identified (N = 1,475). We determined mean nutrient intakes and physiological values between bean consumers and non-consumers. Least square means, standard errors and ANOVA were calculated using appropriate sample weights following adjustment for age, gender, ethnicity and energy. RESULTS: Relative to non-consumers, bean consumers had higher intakes of dietary fiber, potassium, magnesium, iron, and copper (p's < 0.05). Those consuming beans had a lower body weight (p = 0.008) and a smaller waist size (p = 0.043) relative to non-consumers. Additionally, consumers of beans had a 23% reduced risk of increased waist size (p = 0.018) and a 22% reduced risk of being obese (p = 0.026). Also, baked bean consumption was associated with a lower systolic blood pressure. CONCLUSIONS: Bean consumers had better overall nutrient intake levels, better body weights and waist circumferences, and lower systolic blood pressure in comparison to non-consumers. These data support the benefits of bean consumption on improving nutrient intake and health parameters.\",\n \"title\": \"Bean consumption is associated with greater nutrient intake, reduced systolic blood pressure, lower body weight, and a smaller waist circumference ...\"\n },\n {\n \"docid\": \"MED-5078\",\n \"text\": \"In this study, solid fermentation of steamed black soybean with various GRAS (Generally recognized as safe) filamentious-fungi including Aspergillus awamori, Aspergillus oryzae BCRC 30222, Aspergillus sojae BCRC 30103, Rhizopus azygosporus BCRC 31158 and Rhizopus sp. No. 2 was performed. Mutagenicity and antimutagenicity of the methanol extracts of unfermented and fermented steamed black soybeans against 4-nitroquinoline-N-oxide (4-NQO), a direct mutagen and Benzo[a]pyrene (B[a]P), an indirect mutagen, on Salmonella Typhimurium TA100 and TA 98, were examined. The methanol extracts of unfermented and fermented steamed black soybeans show no mutagenic activity for either test strains at the doses tested. The extracts inhibited mutagenesis by either 4-NQO or B[a]P in S. Typhimurium TA100 and TA98. Fermentation with fungi also enhanced the antimutagenic effect of black soybean while the antimutagenic effect of the fermented black soybeans extract varied with the starter organism, mutagen, and test strain of S. Typhimurium examined. Generally, the extracts of A. awamori-fermented black soybean exhibited the highest antimutagenic effect. With strain TA100, the inhibitory effects of 5.0 mg of A. awamori-fermented black soybean extract per plate on the mutagenic effects of 4-NQO and B[a]P were 92% and 89%, respectively, while the corresponding rates for extract of unfermented were 41% and 63%, respectively. With strain 98, the inhibition rates were 94 and 81% for the fermented bean extract and 58% and 44% for the unfermented bean extracts. Testing of extracts prepared from black soybean by A. awamori at temperatures 25, 30 and 35 degrees C and for times of 1-5 days revealed that, generally, the extract prepared from beans fermented at 30 degrees C for 3 days exhibited the greatest inhibition against the mutagenic effects of 4-NQO and B[a]P.\",\n \"title\": \"Mutagenic and antimutagenic effects of methanol extracts of unfermented and fermented black soybeans.\"\n },\n {\n \"docid\": \"MED-4989\",\n \"text\": \"BACKGROUND: A high nutrient density (HND) vegetable-based diet offers a dietary model extremely low in saturated fat as well as refined carbohydrates and emphasizes a liberal intake of fresh fruits, vegetables, beans, and nuts. We conducted a retrospective chart review of patients who came to a family practice office seeking nutritional counseling for weight loss. All of these patients were prescribed an HND diet in an extended counseling session with a family physician. METHODS: A convenience sample (N = 56) of all patients seeking dietary counseling for weight loss from a family practice physician in a 3-year period was included in the chart review. No personal identifying data were recorded. The initial counseling sessions averaged 1 hour in length. Patients were provided with a sample HND daily meal plan and recipes and with verbal and written information about the rationale for the diet. Data recorded from patients' charts at 6-month intervals for up to 2 years of follow-up (when available) included weight, blood pressure, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and cholesterol:HDL ratio. Non-parametric statistical testing using the Friedman rank order (exact) test for k-related samples was conducted. A follow-up survey on adherence and medication use was completed by 38 patients. RESULTS: Of the 33 patients who returned for follow-up after 1 year, the mean weight loss was 31 lbs (P = .000). Of the 19 patients who returned after 2 years, the mean weight loss was 53 lbs (P = .000), mean cholesterol fell by 13 points, LDL by 15 points, triglycerides by 17 points, and cardiac risk ratio dropped from 4.5 to 3.8. Changes in systolic and diastolic blood pressure were highly significant at all follow-up time intervals (P < or = .001). There was a significant correlation between adherence and degree of weight loss (P = .011). CONCLUSIONS: Weight loss was sustained in patients who returned for follow-up and was more substantial in those who reported good adherence to the recommendations. However, many patients were lost to follow-up. Favorable changes in lipid profile and blood pressure were noted. An HND diet has the potential to provide sustainable, significant, long-term weight loss and may provide substantial lowering of cardiac risk in patients who are motivated and provided with extended one-on-one counseling and follow-up visits. Development of tools to aid in patient retention is an area for possible further study. Clinical trials with long-term follow-up are needed to further test the therapeutic potential and to examine adherence and follow-up issues related to this dietary approach. An HND diet as demonstrated with this group may be the most health-favorable and effective way to lose weight for appropriately motivated patients.\",\n \"title\": \"Effect of a high nutrient density diet on long-term weight loss: a retrospective chart review.\"\n },\n {\n \"docid\": \"MED-2010\",\n \"text\": \"Legumes (including alfalfa, clover, lupins, green beans and peas, peanuts, soybeans, dry beans, broad beans, dry peas, chickpeas, and lentils) represent an important component of the human diet in several areas of the world, especially in the developing countries, where they complement the lack of proteins from cereals, roots, and tubers. In some regions of the world, legume seeds are the only protein supply in the diet. The health benefits of legume consumption have received rising interest from researchers, and their consumption and production extends worldwide. Among European countries, higher legume consumption is observed around the Mediterranean, with per capita daily consumption between 8 and 23 g, while in Northern Europe, the daily consumption is less than 5 g per capita. The physiological effects of different legumes vary significantly. These differences may result from the polysaccharides composition, in particular, the quantity and variety of dietary fibers and starch, protein make-up, and variability in phytochemical content. The majority of legumes contain phytochemicals: bioactive compounds, including enzyme inhibitors, phytohemagglutinins (lectins), phytoestrogens, oligosaccharides, saponins, and phenolic compounds, which play metabolic roles in humans who frequently consume these foods. Dietary intake of phytochemicals may provide health benefits, protecting against numerous diseases or disorders, such as coronary heart disease, diabetes, high blood pressure and inflammation. The synergistic or antagonistic effects of these phytochemical mixtures from food legumes, their interaction with other components of the diet, and the mechanism of their action have remained a challenge with regard to understanding the role of phytochemicals in health and diseases. Their mitigating effects and the mechanism of their action need to be further addressed if we are to understand the role of phytochemicals in health and diseases. This review provides an overview of the nutritional quality of legumes and their potential contribution in cardiometabolic risk prevention.\",\n \"title\": \"Nutritional quality of legumes, and their role in cardiometabolic risk prevention: a review.\"\n },\n {\n \"docid\": \"MED-4559\",\n \"text\": \"The cardiovascular risk reduction associated with different statins for the prevention of cardiovascular disease and the cardiovascular risk increase associated with excess dietary intake of fat have been quantified. However, these relative risks have never been directly juxtaposed to determine whether an increase in relative risk by 1 activity could be neutralized by an opposing change in relative risk from a second activity. The investigators compared the increase in relative risk for cardiovascular disease associated with the total fat and trans fat content of fast foods against the relative risk decrease provided by daily statin consumption from a meta-analysis of statins in primary prevention of coronary artery disease (7 randomized controlled trials including 42,848 patients). The risk reduction associated with the daily consumption of most statins, with the exception of pravastatin, is more powerful than the risk increase caused by the daily extra fat intake associated with a 7-oz hamburger (Quarter Pounder) with cheese and a small milkshake. In conclusion, statin therapy can neutralize the cardiovascular risk caused by harmful diet choices. In other spheres of human activity, individuals choosing risky pursuits (motorcycling, smoking, driving) are advised or compelled to use measures to minimize the risk (safety equipment, filters, seatbelts). Likewise, some individuals eat unhealthily. Routine accessibility of statins in establishments providing unhealthy food might be a rational modern means to offset the cardiovascular risk. Fast food outlets already offer free condiments to supplement meals. A free statin-containing accompaniment would offer cardiovascular benefits, opposite to the effects of equally available salt, sugar, and high-fat condiments. Although no substitute for systematic lifestyle improvements, including healthy diet, regular exercise, weight loss, and smoking cessation, complimentary statin packets would add, at little cost, 1 positive choice to a panoply of negative ones.\",\n \"title\": \"Can a statin neutralize the cardiovascular risk of unhealthy dietary choices?\"\n },\n {\n \"docid\": \"MED-5265\",\n \"text\": \"BACKGROUND: Persons following current dietary guidelines have a lower risk of mortality from coronary heart disease. OBJECTIVE: The objective was to compare the short-term effect of a high-fat meal and a high-carbohydrate meal, with and without dietary antioxidants, on vasomotor, antiplatelet, and hemostatic functions of the endothelium in healthy subjects. DESIGN: In an observer-blinded, randomized crossover study, 25 (13 men and 12 women) healthy subjects were given each of 3 meals in random order at 1-wk intervals: a high-fat meal (760 kcal), an isoenergetic high-carbohydrate meal, and a high-fat meal with dietary antioxidants from vegetables (865 kcal). Endothelial functions, as assessed by hemodynamic and rheologic responses to L-arginine--the natural precursor of nitric oxide--were evaluated before and 4 h after each meal. RESULTS: Unlike the high-carbohydrate meal, the high-fat meal increased the plasma concentrations of triacylglycerol (P < 0.01); both meals activated hemostasis. The high-carbohydrate meal did not modify blood pressure, and platelet aggregation decreased in response to the L-arginine load (-7.1 +/- 2.3 mm Hg and -8.5 +/- 4.5%, respectively). After the high-fat meal, the decrease in blood pressure in response to L-arginine was reduced (-1 +/- 0.8 mm Hg), and platelet aggregation showed a paradoxical increase (4.1 +/- 2.1%; P < 0.01 compared with the high-carbohydrate meal). The high-fat meal with antioxidants partially restored the vascular response to L-arginine. CONCLUSION: Compared with a high-carbohydrate meal, a high-fat meal can modify endothelial functions toward a more atherogenetic profile, which is partially prevented by dietary antioxidants.\",\n \"title\": \"Effect of dietary antioxidants on postprandial endothelial dysfunction induced by a high-fat meal in healthy subjects.\"\n },\n {\n \"docid\": \"MED-5153\",\n \"text\": \"OBJECTIVES: We sought to investigate whether the addition of walnuts or olive oil to a fatty meal have differential effects on postprandial vasoactivity, lipoproteins, markers of oxidation and endothelial activation, and plasma asymmetric dimethylarginine (ADMA). BACKGROUND: Compared with a Mediterranean diet, a walnut diet has been shown to improve endothelial function in hypercholesterolemic patients. We hypothesized that walnuts would reverse postprandial endothelial dysfunction associated with consumption of a fatty meal. METHODS: We randomized in a crossover design 12 healthy subjects and 12 patients with hypercholesterolemia to 2 high-fat meal sequences to which 25 g olive oil or 40 g walnuts had been added. Both test meals contained 80 g fat and 35% saturated fatty acids, and consumption of each meal was separated by 1 week. Venipunctures and ultrasound measurements of brachial artery endothelial function were performed after fasting and 4 h after test meals. RESULTS: In both study groups, flow-mediated dilation (FMD) was worse after the olive oil meal than after the walnut meal (p = 0.006, time-period interaction). Fasting, but not postprandial, triglyceride concentrations correlated inversely with FMD (r = -0.324; p = 0.024). Flow-independent dilation and plasma ADMA concentrations were unchanged, and the concentration of oxidized low-density lipoproteins decreased (p = 0.051) after either meal. The plasma concentrations of soluble inflammatory cytokines and adhesion molecules decreased (p < 0.01) independently of meal type, except for E-selectin, which decreased more (p = 0.033) after the walnut meal. CONCLUSIONS: Adding walnuts to a high-fat meal acutely improves FMD independently of changes in oxidation, inflammation, or ADMA. Both walnuts and olive oil preserve the protective phenotype of endothelial cells.\",\n \"title\": \"Acute effects of high-fat meals enriched with walnuts or olive oil on postprandial endothelial function.\"\n },\n {\n \"docid\": \"MED-5075\",\n \"text\": \"The isothiocyanate, sulforaphane, has been implicated in the cancer-protective effects of brassica vegetables. When broccoli is consumed, sulforaphane is released from hydrolysis of glucoraphanin by plant myrosinase and/or colonic microbiota. The influence of meal composition and broccoli-cooking duration on isothiocyanate uptake was investigated in a designed experiment. Volunteers (n 12) were each offered a meal, with or without beef, together with 150 g lightly cooked broccoli (microwaved 2.0 min) or fully cooked broccoli (microwaved 5.5 min), or a broccoli seed extract. They received 3 g mustard containing pre-formed allyl isothiocyanate (AITC) with each meal. Urinary output of allyl (AMA) and sulforaphane (SFMA) mercapturic acids, the biomarkers of production of AITC and sulforaphane respectively, were measured for 24 h after meal consumption. The estimated yield of sulforaphane in vivo was about 3-fold higher after consumption of lightly cooked broccoli than fully cooked broccoli. Absorption of AITC from mustard was about 1.3-fold higher following consumption of the meat-containing meal compared with the non meat-containing alternative. The meal matrix did not significantly influence the hydrolysis of glucoraphanin and its excretion as SFMA from broccoli. Isothiocyanates may interact with the meal matrix to a greater extent if they are ingested pre-formed rather than after their production from hydrolysis of glucosinolates in vivo. The main influence on the production of isothiocyanates in vivo is the way in which brassica vegetables are cooked, rather than the effect of the meal matrix.\",\n \"title\": \"Effect of meal composition and cooking duration on the fate of sulforaphane following consumption of broccoli by healthy human subjects.\"\n },\n {\n \"docid\": \"MED-5261\",\n \"text\": \"OBJECTIVE—To examine the acute effects of consumption of monounsaturated (MUFAs) and saturated fatty acids (SAFAs) on endothelial function in subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS—A total of 33 participants were examined after consumption of two different isocaloric meals: one rich in MUFA and one rich in SAFA, in the form of extra-virgin olive oil and butter, respectively. Endothelial function was assessed by determination of flow-mediated dilatation (FMD). RESULTS—FMD did not change significantly after the MUFA-rich meal but declined after the SAFA-rich meal. The FMD during the experiment, expressed as incremental area under the curve, increased after the MUFA-rich meal by 5.2 ± 2.5% and decreased after the SAFA-rich meal by 16.7 ± 6.0% (Δ = −11.5 ± 6.4%; P = 0.008). CONCLUSIONS—Consumption of an SAFA-rich meal is harmful for the endothelium, while a MUFA-rich meal does not impair endothelial function in subjects with type 2 diabetes.\",\n \"title\": \"Differential Effects of Two Isoenergetic Meals Rich in Saturated or Monounsaturated Fat on Endothelial Function in Subjects With Type 2 Diabetes\"\n },\n {\n \"docid\": \"MED-2147\",\n \"text\": \"Consumption of Phaseolus vulgaris bean species such as pinto, black, navy or kidney may be beneficial in the prevention and treatment of chronic diseases. In particular, conditions that are promoted by increased glycaemic stress (hyperglycaemia and hyperinsulinaemia) including diabetes, CVD and cancer seem to be reduced in individuals who eat more of these beans. The present paper discusses the influence of P. vulgaris species on glycaemic response and the impact that relationship may have on the risk of developing diabetes, CVD and cancer.\",\n \"title\": \"Phaseolus beans: impact on glycaemic response and chronic disease risk in human subjects.\"\n },\n {\n \"docid\": \"MED-2580\",\n \"text\": \"Adequate fruit and vegetable intake was suggested to protect against colorectal cancer and colorectal adenomas; however, several recent prospective studies reported no association. We examined the association between fruits and vegetables and adenomatous polyp recurrence in the Polyp Prevention Trial (PPT). The PPT was a low-fat, high-fiber, high-fruit, and vegetable dietary intervention trial of adenoma recurrence, in which there were no differences in the rate of adenoma recurrence in participants in the intervention and control arms of the trial. In this analysis of the entire PPT trial–based cohort, multiple logistic regression analysis was used to estimate the odds ratio (OR) of advanced and nonadvanced adenoma recurrence within quartiles of baseline and change (baseline minus the mean over 3 y) in fruit and vegetable intake, after adjustment for age, total energyy intake, use of nonsteroidal anti-inflammatory drugs, BMI, and gender. There were no significant associations between nonadvanced adenoma recurrence and overall change in fruit and vegetable consumption; however, those in the highest quartile of change in dry bean intake (greatest increase) compared with those in the lowest had a significantly reduced OR for advanced adenoma recurrence (OR = 0.35; 95% CI, 0.18–0.69; P for trend = 0.001). The median in the highest quartile of change in dry bean intake was 370% higher than the baseline intake. The PPT trial–based cohort provides evidence that dry beans may be inversely associated with advanced adenoma recurrence.\",\n \"title\": \"High Dry Bean Intake and Reduced Risk of Advanced Colorectal Adenoma Recurrence among Participants in the Polyp Prevention Trial\"\n },\n {\n \"docid\": \"MED-5118\",\n \"text\": \"OBJECTIVE: To compare the effects of two commercially available soy milks (one made using whole soy beans, the other using soy protein isolate) with low-fat dairy milk on plasma lipid, insulin, and glucose responses. DESIGN: Randomized clinical trial, cross-over design. SUBJECTS: Participants were 30-65 years of age, n = 28, with pre-study LDL-cholesterol (LDL-C) concentrations of 160-220 mg/dL, not on lipid lowering medications, and with an overall Framingham risk score of or=4 weeks. RESULTS: Mean LDL-C concentration at the end of each phase (+/- SD) was 161 +/- 20, 161 +/- 26 and 170 +/- 24 mg/dL for the whole bean soy milk, the soy protein isolate milk, and the dairy milk, respectively (p = 0.9 between soy milks, p = 0.02 for each soy milk vs. dairy milk). No significant differences by type of milk were observed for HDL-cholesterol, triacylglycerols, insulin, or glucose. CONCLUSION: A 25 g dose of daily soy protein from soy milk led to a modest 5% lowering of LDL-C relative to dairy milk among adults with elevated LDL-C. The effect did not differ by type of soy milk and neither soy milk significantly affected other lipid variables, insulin or glucose.\",\n \"title\": \"Effect of two types of soy milk and dairy milk on plasma lipids in hypercholesterolemic adults: a randomized trial.\"\n },\n {\n \"docid\": \"MED-5013\",\n \"text\": \"INTRODUCTION: Endothelial dysfunction is known to occur in patients with coronary artery disease. Flow-mediated dilation of the brachial artery using Doppler ultrasound is a non-invasive technique for the assessment of endothelial function. The objective of the study was to use the above method to evaluate the pathophysiology of high-fat (HF) intake on endothelial function in a local population. A popular local dish \\\"nasi-lemak\\\", a source of high saturated fat content from coconut milk, was chosen to represent a local high-fat meal (LHF). In addition, the effects of a Western high-fat (WHF) (\\\"McDonald's\\\") meal and a low-fat (LF) meal control on endothelial function were studied. MATERIALS AND METHODS: The study population consisted of 10 healthy male non-smoker (mean age 22 +/- 2 years) with normal body mass index, normal fasting sugar and lipid profiles. Nitric oxide dependent flow-mediated dilation and nitric oxide independent (GTN) dilation was assessed by Doppler flow in the brachial artery before and 4 hours after each meal on separate occasions by 2 experienced sonographers blinded to the type of meals. RESULTS: The baseline brachial artery size, baseline vessel flow and increase in flow after cuff deflation were similar for each of the six arterial studies. In response to reactive hyperaemia after cuff deflation, the endothelium-dependent dilation was significantly different between the meals. There was a marked decrease in endothelium-dependent dilation after the WHF meal compared to the LF meal (8.6 +/- 2.2% vs. -0.8 +/- 1.1%, P < 0.006). There was also a marked decrease in endothelium-dependent dilation after the LHF meal compared to the LF meal (7.7 +/- 2.1% vs. -0.8 +/- 1.1%, P < 0.001). When comparing between the two HF meals, the change in endothelium-dependent dilation was not significant (7.7 vs. 8.6%, P = 0.678). GTN-induced dilation was not significantly different before and after the LF, WHF or LHF (0.1 +/- 0.5% vs. 0.2 +/- 0.9% vs. 1.3 +/- 0.5%, P = 0.094). CONCLUSION: The results suggest that in a local population, impairment of endothelial function is a possible mechanism in the pathophysiology of atherosclerosis from HF intake, beyond just affecting lipid levels. This effect is observed after both a LHF and a WHF meal intake. This technique to study endothelial function may be a useful non-invasive screening tool in the study of other HF diet choices and provides further information for the education of the influence of dietary choices on atherosclerosis.\",\n \"title\": \"Impairment of endothelial function--a possible mechanism for atherosclerosis of a high-fat meal intake.\"\n },\n {\n \"docid\": \"MED-1968\",\n \"text\": \"Our aim was to determine the effects of increasing amounts of dietary cholesterol (0-710 mg) on the postprandial plasma lipid responses and lipoprotein changes in normolipidemic human subjects. Ten subjects were fed five different test meals in a random order: one meal did not contain fat or cholesterol while the four others contained a fixed amount of lipids (45 g) and 0, 140, 280, and 710 mg cholesterol, respectively. Fasting and post-meal blood samples were obtained for 7 h. Large and small triglyceride-rich lipoproteins (TRL), low density (LDL), and high density (HDL) lipoproteins were isolated. Compared to the no-fat, no-cholesterol meal, the fat-enriched meals raised (P < 0.05) plasma triglycerides, phospholipids, and free cholesterol and lowered cholesteryl esters postprandially. The meals containing zero or 140 mg cholesterol generally elicited comparable postprandial plasma and lipoprotein lipid responses. The meals providing 280 or 710 mg cholesterol significantly increased postprandial plasma phospholipids and large TRL triglycerides and decreased plasma esterified cholesterol. The lipid composition of the large TRLs and the concentrations of the small TRL lipid components were not altered postprandially by cholesterol intake. On the other hand, LDL free cholesterol increased after 3 h, LDL cholesteryl esters dropped after 3 and 7 h, HDL cholesteryl esters dropped after 3 h, and HDL phospholipids increased 7 h after ingesting meals highly enriched in cholesterol. Blood insulin, apoA-I and apoB were not altered postprandially by cholesterol intake. Thus, the data show that ingesting more than 140 mg cholesterol per meal significantly alters the postprandial lipoprotein response in healthy subjects.\",\n \"title\": \"Effects of increasing amounts of dietary cholesterol on postprandial lipemia and lipoproteins in human subjects.\"\n },\n {\n \"docid\": \"MED-2253\",\n \"text\": \"Twenty three adults ingested 203Pb as lead acetate on the 12th hour of a 19 h fast. Retention measured 7 days later in a whole-body counter was 61% and whole-body turnover rates suggested that initial uptake had been considerably greater. Balanced meals eaten with 203Pb reduced lead uptake to 4% and the influence of the food lasted for up to 3 h. The effects of phytate, ethylene-diaminetetra acetate (EDTA), caffeine, alcohol, glucose, a liquid meal and a light snack were tested separately with intermediate results. The effect of a meal was probably largely due to its content of calcium and phosphate salts but lead uptake was probably further reduced by phytate which is plentiful in whole cereals and it was probably increased by a factor in milk. Uptake with skimmed milk was the same as with whole milk and we suggested that the factor was not fat. Comestibles with low mineral and phytate contents reduced lead uptake by intermediate amounts, possibly by stimulation of digestive secretions. The avid uptake of lead during a fast, the large reduction of lead uptake with meals and the likelihood of variations in gastric-emptying rates and dietary habits may be major causes of variation in body burdens of lead in the population.\",\n \"title\": \"Effects of meals and meal times on uptake of lead from the gastrointestinal tract in humans.\"\n },\n {\n \"docid\": \"MED-5271\",\n \"text\": \"OBJECTIVES: This study investigated the postprandial effect of components of the Mediterranean diet on endothelial function, which may be an atherogenic factor. BACKGROUND: The Mediterranean diet, containing olive oil, pasta, fruits, vegetables, fish, and wine, is associated with an unexpectedly low rate of cardiovascular events. The Lyon Diet Heart Study found that a Mediterranean diet, which substituted omega-3-fatty-acid-enriched canola oil for the traditionally consumed omega-9 fatty-acid-rich olive oil, reduced cardiovascular events. METHODS: We fed 10 healthy, normolipidemic subjects five meals containing 900 kcal and 50 g fat. Three meals contained different fat sources: olive oil, canola oil, and salmon. Two olive oil meals also contained antioxidant vitamins (C and E) or foods (balsamic vinegar and salad). We measured serum lipoproteins and glucose and brachial artery flow-mediated vasodilation (FMD), an index of endothelial function, before and 3 h after each meal. RESULTS: All five meals significantly raised serum triglycerides, but did not change other lipoproteins or glucose 3 h postprandially. The olive oil meal reduced FMD 31% (14.3 +/- 4.2% to 9.9 +/- 4.5%, p = 0.008). An inverse correlation was observed between postprandial changes in serum triglycerides and FMD (r = -0.47, p < 0.05). The remaining four meals did not significantly reduce FMD. CONCLUSIONS: In terms of their postprandial effect on endothelial function, the beneficial components of the Mediterranean and Lyon Diet Heart Study diets appear to be antioxidant-rich foods, including vegetables, fruits, and their derivatives such as vinegar, and omega-3-rich fish and canola oils.\",\n \"title\": \"The postprandial effect of components of the Mediterranean diet on endothelial function.\"\n },\n {\n \"docid\": \"MED-4318\",\n \"text\": \"Preliminary data in the literature indicate that iron absorption from a meal may be increased when consumed with low-pH beverages such as cola, and it is also possible that sugar iron complexes may alter iron availability. A randomized, crossover trial was conducted to compare the bioavailability of nonheme iron from a vegetarian pizza meal when consumed with 3 different beverages (cola, diet cola, and mineral water). Sixteen women with serum ferritin concentrations of 11-54 µg/L were recruited and completed the study. The pizza meal contained native iron and added ferric chloride solution as a stable isotope extrinsic label; the total iron content of the meal was ~5.3 mg. Incorporation of iron from the meal into RBC was not affected by the type of drink (9.9% with cola, 9.4% with diet cola, and 9.6% with water). Serum ferritin and plasma hepcidin were correlated (r = 0.66; P<0.001) and both were significant predictors of iron bioavailability, but their combined effect explained only 30% of the inter-individual variation (P<0.001) and illustrates the current lack of understanding of mechanisms responsible for the fine-tuning of iron absorption. Although there was no effect of low-pH drinks on iron bioavailability in healthy women, their effect on absorption of fortification iron that requires solubilization in dilute acid, such as reduced iron, and in individuals with low gastric acid production, such as older people and individuals with Helicobacter pylori infection, warrants further investigation.\",\n \"title\": \"Low-pH cola beverages do not affect women's iron absorption from a vegetarian meal.\"\n },\n {\n \"docid\": \"MED-760\",\n \"text\": \"There is much interest in the potential of dietary antioxidants to attenuate in vivo oxidative stress, but little characterization of the time course of plasma effects exists. Culinary spices have demonstrated potent in vitro antioxidant properties. The objective of this study was to examine whether adding 14 g of a high antioxidant spice blend to a 5060-kJ (1200 kcal) meal exerted significant postprandial effects on markers of plasma antioxidant status and metabolism. Healthy overweight men (n = 6) consumed a control and spiced meal in a randomized crossover design with 1 wk between testing sessions. Blood was sampled prior to the meal and at 30-min intervals for 3.5 h (total of 8 samples). Mixed linear models demonstrated a treatment × time interaction (P < 0.05) for insulin and TG, corresponding with 21 and 31% reductions in postprandial levels with the spiced meal, respectively. Adding spices to the meal significantly increased the ferric reducing antioxidant power, such that postprandial increases following the spiced meal were 2-fold greater than after the control meal (P = 0.009). The hydrophilic oxygen radical absorbance capacity (ORAC) of plasma also was increased by spices (P = 0.02). There were no treatment differences in glucose, total thiols, lipophilic ORAC, or total ORAC. The incorporation of spices into the diet may help normalize postprandial insulin and TG and enhance antioxidant defenses.\",\n \"title\": \"A High Antioxidant Spice Blend Attenuates Postprandial Insulin and Triglyceride Responses and Increases Some Plasma Measures of Antioxidant Activity in Healthy, Overweight Men\"\n }\n]"}}},{"rowIdx":179,"cells":{"query_id":{"kind":"string","value":"PLAIN-2625"},"query":{"kind":"string","value":"Turmeric Curcumin Reprogramming Cancer Cell Death"},"positive_passages":{"kind":"list like","value":[{"docid":"MED-2781","text":"Our previous study demonstrated that curcumin, an active compound of Curcuma xanthorrhiza and C. domestica, produces a positive cholekinetic effect. A 20 mg amount of curcumin is capable of contracting the gall bladder by up to 29% within an observation time of 2 h. The aim of the current study was to define the dosage of curcumin capable of producing a 50% contraction of the gall bladder, and to determine if there is a linear relationship between doubling the curcumin dosage and the doubling of gall bladder contraction. A randomised, single-blind, three-phase, crossover-designed examination was carried out on 12 healthy volunteers. Ultrasonography was carried out serially to measure the gall bladder volume. The data obtained was analysed by analysis of variance (ANOVA). The fasting volumes of gall bladders were similar (P > 0.50), with 17.28 +/- 5.47 mL for 20 mg curcumin, 18.34 +/- 3.75 mL for 40 mg and 18.24 +/- 3.72 mL for 80 mg. The percentage decrease in gall bladder volume 2 h after administration of 20, 40 and 80 mg was 34.10 +/- 10.16, 51.15 +/- 8.08 and 72.25 +/- 8.22, respectively, which was significantly different (P < 0.01). On the basis of the present findings, it appears that the dosage of cucumin capable of producing a 50% contraction of the bladder was 40 mg. This study did not show any linear relationship between doubling curcumin dosage and the doubling of gall bladder contraction.","title":"Effect of different curcumin dosages on human gall bladder."},{"docid":"MED-2819","text":"OBJECTIVES: Curcumin (diferuloylmethane) is the principal biochemical component of the spice turmeric and has been shown to possess potent anti-catabolic, anti-inflammatory and antioxidant, properties. This article aims to provide a summary of the actions of curcumin on articular chondrocytes from the available literature with the use of a text-mining tool. We highlight both the potential benefits and drawbacks of using this chemopreventive agent for treating osteoarthritis (OA). We also explore the recent literature on the molecular mechanisms of curcumin mediated alterations in gene expression mediated via activator protein 1 (AP-1)/nuclear factor-kappa B (NF-kappaB) signalling in chondrocytes, osteoblasts and synovial fibroblasts. METHODS: A computer-aided search of the PubMed/Medline database aided by a text-mining tool to interrogate the ResNet Mammalian database 6.0. RESULTS: Recent work has shown that curcumin protects human chondrocytes from the catabolic actions of interleukin-1 beta (IL-1beta) including matrix metalloproteinase (MMP)-3 up-regulation, inhibition of collagen type II and down-regulation of beta1-integrin expression. Curcumin blocks IL-1beta-induced proteoglycan degradation, AP-1/NF-kappaB signalling, chondrocyte apoptosis and activation of caspase-3. CONCLUSIONS: The available data from published in vitro and in vivo studies suggest that curcumin may be a beneficial complementary treatment for OA in humans and companion animals. Nevertheless, before initiating extensive clinical trials, more basic research is required to improve its solubility, absorption and bioavailability and gain additional information about its safety and efficacy in different species. Once these obstacles have been overcome, curcumin and structurally related biochemicals may become safer and more suitable nutraceutical alternatives to the non-steroidal anti-inflammatory drugs that are currently used for the treatment of OA. Copyright 2009 Osteoarthritis Research Society International. All rights reserved.","title":"Biological actions of curcumin on articular chondrocytes."},{"docid":"MED-2825","text":"Turmeric, a dried powder derived from the rhizome of Curcuma longa, has been used for centuries in certain parts of the world and has been linked to numerous biological activities including antioxidant, anti-inflammatory, anticancer, antigrowth, anti-arthritic, anti-atherosclerotic, antidepressant, anti-aging, antidiabetic, antimicrobial, wound healing, and memory-enhancing activities. One component of turmeric is curcumin, which has been extensively studied, as indicated by more than 5600 citations, most of which have appeared within the past decade. Recent research has identified numerous chemical entities from turmeric other than curcumin. It is unclear whether all of the activities ascribed to turmeric are due to curcumin or whether other compounds in turmeric can manifest these activities uniquely, additively, or synergistically with curcumin. However, studies have indicated that turmeric oil, present in turmeric, can enhance the bioavailability of curcumin. Studies over the past decade have indicated that curcumin-free turmeric (CFT) components possess numerous biological activities including anti-inflammatory, anticancer, and antidiabetic activities. Elemene derived from turmeric is approved in China for the treatment of cancer. The current review focuses on the anticancer and anti-inflammatory activities exhibited by CFT and by some individual components of turmeric, including turmerin, turmerone, elemene, furanodiene, curdione, bisacurone, cyclocurcumin, calebin A, and germacrone. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.","title":"Curcumin-free turmeric exhibits anti-inflammatory and anticancer activities: Identification of novel components of turmeric."},{"docid":"MED-4239","text":"BACKGROUND: Prostate cancer is the most common solid-tumor cancer in US males but is rare in Asian males. When Asian men adopt the US lifestyle, clinical prostate cancer increases greatly. Epidemiological data from men in the US indicate that regular activity may reduce the risk for prostate cancer. METHODS: Serum was obtained from three groups of similar-aged men, Control, Diet and Exercise, and Exercise alone were used to stimulate LNCaP cells in culture. Growth and apoptosis of tumor cells were measured. Serum samples were also used to measure insulin, IGF-1, IGFBP-1. RESULTS: The Diet and Exercise and the Exercise alone groups had lower serum insulin and IGF-1 but higher IGFBP-1 compared to Controls. LNCaP cell growth was reduced in both groups compared to Control and there was a major increase in apoptosis of tumor cells. CONCLUSIONS: A low-fat diet and/or intensive exercise results in change in serum hormones and growth factors in vivo that can reduce growth and induce apoptosis of LNCaP prostate tumor cells in vitro. Copyright 2003 Wiley-Liss, Inc.","title":"A low-fat diet and/or strenuous exercise alters the IGF axis in vivo and reduces prostate tumor cell growth in vitro."},{"docid":"MED-2812","text":"Curcumin derived from the tropical plant Curcuma longa has a long history of use as a dietary agent, food preservative, and in traditional Asian medicine. It has been used for centuries to treat biliary disorders, anorexia, cough, diabetic wounds, hepatic disorders, rheumatism, and sinusitis. The preventive and therapeutic properties of curcumin are associated with its antioxidant, anti-inflammatory, and anticancer properties. Extensive research over several decades has attempted to identify the molecular mechanisms of curcumin action. Curcumin modulates numerous molecular targets by altering their gene expression, signaling pathways, or through direct interaction. Curcumin regulates the expression of inflammatory cytokines (e.g., TNF, IL-1), growth factors (e.g., VEGF, EGF, FGF), growth factor receptors (e.g., EGFR, HER-2, AR), enzymes (e.g., COX-2, LOX, MMP9, MAPK, mTOR, Akt), adhesion molecules (e.g., ELAM-1, ICAM-1, VCAM-1), apoptosis related proteins (e.g., Bcl-2, caspases, DR, Fas), and cell cycle proteins (e.g., cyclin D1). Curcumin modulates the activity of several transcription factors (e.g., NF-κB, AP-1, STAT) and their signaling pathways. Based on its ability to affect multiple targets, curcumin has the potential for the prevention and treatment of various diseases including cancers, arthritis, allergies, atherosclerosis, aging, neurodegenerative disease, hepatic disorders, obesity, diabetes, psoriasis, and autoimmune diseases. This review summarizes the molecular mechanisms of modulation of gene expression by curcumin. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.","title":"Molecular mechanisms of curcumin action: gene expression."},{"docid":"MED-2604","text":"Cancer is a hyperproliferative disorder that is usually treated by chemotherapeutic agents that are toxic not only to tumor cells but also to normal cells, so these agents produce major side effects. In addition, these agents are highly expensive and thus not affordable for most. Moreover, such agents cannot be used for cancer prevention. Traditional medicines are generally free of the deleterious side effects and usually inexpensive. Curcumin, a component of turmeric (Curcuma longa), is one such agent that is safe, affordable, and efficacious. How curcumin kills tumor cells is the focus of this review. We show that curcumin modulates growth of tumor cells through regulation of multiple cell signaling pathways including cell proliferation pathway (cyclin D1, c-myc), cell survival pathway (Bcl-2, Bcl-xL, cFLIP, XIAP, c-IAP1), caspase activation pathway (caspase-8, 3, 9), tumor suppressor pathway (p53, p21) death receptor pathway (DR4, DR5), mitochondrial pathways, and protein kinase pathway (JNK, Akt, and AMPK). How curcumin selectively kills tumor cells, and not normal cells, is also described in detail.","title":"Curcumin and Cancer Cells: How Many Ways Can Curry Kill Tumor Cells Selectively?"},{"docid":"MED-2605","text":"Curcumin (diferuloylmethane), the yellow pigment in turmeric (Curcuma longa), is known to inhibit proliferation of cancer cells by arresting them at various phases of the cell cycle and to induce apoptosis in tumor cells. Curcumin-induced apoptosis mainly involves the activation of caspase-3 and mitochondria-mediated pathway in various cancer cells of different tissue origin. In the present study, the induction of apoptosis and cytotoxicity by curcumin in colon cancer colo 205 cells was investigated by using flow cytometry. The results demonstrated that curcumin induced cytotoxicity and apoptosis dose- and time-depedently. Curcumin induced the production of reactive oxygen species (ROS) and Ca+2, decreased the levels of mitochondria membrane potential and induced caspase-3 activity. Curcumin also promoted the expression of Bax, cytochrome C, p53 and p21 but inhibited the expression of Bcl-2. These observations suggest that curcumin may have a possible therapeutic potential in colon cancer patients.","title":"Curcumin-induced apoptosis of human colon cancer colo 205 cells through the production of ROS, Ca2+ and the activation of caspase-3."},{"docid":"MED-2826","text":"Background Curcumin extracts of turmeric are proposed to produce health benefits. To date, human intervention studies have focused mainly on people with existing health problems given high doses of poorly absorbed curcumin. The purpose of the current study was to check whether in healthy people, a low dose of a lipidated curcumin extract could alter wellness-related measures. Methods The present study was conducted in healthy middle aged people (40–60 years old) with a low dose of curcumin (80 mg/day) in a lipidated form expected to have good absorption. Subjects were given either curcumin (N = 19) or placebo (N = 19) for 4 wk. Blood and saliva samples were taken before and after the 4 weeks and analyzed for a variety of blood and saliva measures relevant to health promotion. Results Curcumin, but not placebo, produced the following statistically significant changes: lowering of plasma triglyceride values, lowering of salivary amylase levels, raising of salivary radical scavenging capacities, raising of plasma catalase activities, lowering of plasma beta amyloid protein concentrations, lowering of plasma sICAM readings, increased plasma myeloperoxidase without increased c-reactive protein levels, increased plasma nitric oxide, and decreased plasma alanine amino transferase activities. Conclusion Collectively, these results demonstrate that a low dose of a curcumin-lipid preparation can produce a variety of potentially health promoting effects in healthy middle aged people.","title":"Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people"},{"docid":"MED-2794","text":"Turmeric, a plant rhizome that is often dried, ground and used as a cooking spice, has also been used medicinally for several thousand years. Curcumin, the phytochemical that gives turmeric its golden color, is responsible for most of the therapeutic effects of turmeric. In recent years curcumin has been studied for its effects on chronic diseases such as diabetes, Alzheimer's, and cancer. Though many researchers are investigating turmeric/curcumin in cancer therapy, there is little epidemiologic information on the effects of turmeric consumption. With limited availability of pharmacologic interventions in many areas of the world, use of turmeric in the diet may help to alleviate some of the disease burden through prevention. Here we provide a brief overview of turmeric consumption in different parts of the world, cancer rates in those regions, possible biochemical mechanisms by which turmeric acts and practical recommendations based on the information available.","title":"Dietary turmeric potentially reduces the risk of cancer."},{"docid":"MED-2814","text":"Curcumin (diferuloylmethane), an active constituent of turmeric, is a well-described phytochemical, which has been used since ancient times for the treatment of various diseases. The dysregulation of cell signaling pathways by the gradual alteration of regulatory proteins is the root cause of cancers. Curcumin modulates regulatory proteins through various molecular mechanisms. Several research studies have provided in-depth analysis of multiple targets through which curcumin induces protective effects against cancers including gastrointestinal, genitourinary, gynecological, hematological, pulmonary, thymic, brain, breast, and bone. The molecular mechanisms of action of curcumin in treating different types of cancers remain under investigation. The multifaceted role of this dietary agent is mediated through its inhibition of several cell signaling pathways at multiple levels. Curcumin has the ability to inhibit carcinogenicity through the modulation of the cell cycle by binding directly and indirectly to molecular targets including transcription factors (NF-kB, STAT3, β-catenin, and AP-1), growth factors (EGF, PDGF, and VEGF), enzymes (COX-2, iNOS, and MMPs), kinases (cyclin D1, CDKs, Akt, PKC, and AMPK), inflammatory cytokines (TNF, MCP, IL-1, and IL-6), upregulation of proapoptotic (Bax, Bad, and Bak) and downregulation of antiapoptotic proteins (Bcl(2) and Bcl-xL). A variety of animal models and human studies have proven that curcumin is safe and well tolerated even at very high doses. This study elaborates the current understanding of the chemopreventive effects of curcumin through its multiple molecular pathways and highlights its therapeutic value in the treatment and prevention of a wide range of cancers. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.","title":"Curcumin in various cancers."},{"docid":"MED-2810","text":"Although turmeric (Curcuma longa; an Indian spice) has been described in Ayurveda, as a treatment for inflammatory diseases and is referred by different names in different cultures, the active principle called curcumin or diferuloylmethane, a yellow pigment present in turmeric (curry powder) has been shown to exhibit numerous activities. Extensive research over the last half century has revealed several important functions of curcumin. It binds to a variety of proteins and inhibits the activity of various kinases. By modulating the activation of various transcription factors, curcumin regulates the expression of inflammatory enzymes, cytokines, adhesion molecules, and cell survival proteins. Curcumin also downregulates cyclin D1, cyclin E and MDM2; and upregulates p21, p27, and p53. Various preclinical cell culture and animal studies suggest that curcumin has potential as an antiproliferative, anti-invasive, and antiangiogenic agent; as a mediator of chemoresistance and radioresistance; as a chemopreventive agent; and as a therapeutic agent in wound healing, diabetes, Alzheimer disease, Parkinson disease, cardiovascular disease, pulmonary disease, and arthritis. Pilot phase I clinical trials have shown curcumin to be safe even when consumed at a daily dose of 12g for 3 months. Other clinical trials suggest a potential therapeutic role for curcumin in diseases such as familial adenomatous polyposis, inflammatory bowel disease, ulcerative colitis, colon cancer, pancreatic cancer, hypercholesteremia, atherosclerosis, pancreatitis, psoriasis, chronic anterior uveitis and arthritis. Thus, curcumin, a spice once relegated to the kitchen shelf, has moved into the clinic and may prove to be \"Curecumin\".","title":"Curcumin as \"Curecumin\": from kitchen to clinic."},{"docid":"MED-2599","text":"Curcumin exhibits anti-inflammatory and antitumor activities. Although its functional mechanism has not been elucidated so far, numerous studies have shown that curcumin induces apoptosis in cancer cells. In the present study, we show that subtoxic concentrations of curcumin sensitize human renal cancer cells to the tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-mediated apoptosis. This apoptosis induced by the combination of curcumin and TRAIL is not interrupted by Bcl-2 overexpression. We found that treatment with curcumin significantly induces death receptor 5 (DR5) expression both at its mRNA and protein levels, accompanying the generation of the reactive oxygen species (ROS). Not only the pretreatment with N-acetylcystine but also the ectopic expression of peroxiredoxin II, an antioxidative protein, dramatically inhibited the apoptosis induced by curcumin and TRAIL in combination, blocking the curcumin-mediated DR5 upregulation. Taken together, the present study demonstrates that curcumin enhances TRAIL-induced apoptosis by ROS-mediated DR5 upregulation.","title":"Curcumin sensitizes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through reactive oxygen species-mediated upre..."},{"docid":"MED-5337","text":"PURPOSE: Men with prostate cancer are often advised to make changes in diet and lifestyle, although the impact of these changes has not been well documented. Therefore, we evaluated the effects of comprehensive lifestyle changes on prostate specific antigen (PSA), treatment trends and serum stimulated LNCaP cell growth in men with early, biopsy proven prostate cancer after 1 year. MATERIALS AND METHODS: Patient recruitment was limited to men who had chosen not to undergo any conventional treatment, which provided an unusual opportunity to have a nonintervention randomized control group to avoid the confounding effects of interventions such as radiation, surgery or androgen deprivation therapy. A total of 93 volunteers with serum PSA 4 to 10 ng/ml and cancer Gleason scores less than 7 were randomly assigned to an experimental group that was asked to make comprehensive lifestyle changes or to a usual care control group. RESULTS: None of the experimental group patients but 6 control patients underwent conventional treatment due to an increase in PSA and/or progression of disease on magnetic resonance imaging. PSA decreased 4% in the experimental group but increased 6% in the control group (p = 0.016). The growth of LNCaP prostate cancer cells (American Type Culture Collection, Manassas, Virginia) was inhibited almost 8 times more by serum from the experimental than from the control group (70% vs 9%, p <0.001). Changes in serum PSA and also in LNCaP cell growth were significantly associated with the degree of change in diet and lifestyle. CONCLUSIONS: Intensive lifestyle changes may affect the progression of early, low grade prostate cancer in men. Further studies and longer term followup are warranted.","title":"Intensive lifestyle changes may affect the progression of prostate cancer."},{"docid":"MED-2805","text":"Obesity is a significant risk factor for developing osteoarthritis in weight-bearing and non-weight-bearing joints. Although the pathogenesis of obesity-associated osteoarthritis is not completely understood, recent studies indicate that pro-inflammatory metabolic factors contribute to an increase in osteoarthritis risk. Adipose tissue, and in particular infrapatellar fat, is a local source of pro-inflammatory mediators that are increased with obesity and have been shown to increase cartilage degradation in cell and tissue culture models. One adipokine in particular, leptin, may be a critical mediator of obesity-associated osteoarthritis via synergistic actions with other inflammatory cytokines. Biomechanical factors may also increase the risk of osteoarthritis by activating cellular inflammation and promoting oxidative stress. However, some types of biomechanical stimulation, such as physiologic cyclic loading, inhibit inflammation and protect against cartilage degradation. A high percentage of obese individuals with knee osteoarthritis are sedentary, suggesting that a lack of physical activity may increase the susceptibility to inflammation. A more comprehensive approach to understanding how obesity alters daily biomechanical exposures within joint tissues may provide new insight into the protective and damaging effects of biomechanical factors on inflammation in osteoarthritis.","title":"Pathobiology of obesity and osteoarthritis: integrating biomechanics and inflammation"},{"docid":"MED-2815","text":"Curcumin, an active polyphenol of the golden spice turmeric, is a highly pleiotropic molecule with the potential to modulate the biological activity of a number of signaling molecules. Traditionally, this polyphenol has been used in Asian countries to treat such human ailments as acne, psoriasis, dermatitis, and rash. Recent studies have indicated that curcumin can target newly identified signaling pathways including those associated with microRNA, cancer stem cells, and autophagy. Extensive research from preclinical and clinical studies has delineated the molecular basis for the pharmaceutical uses of this polyphenol against cancer, pulmonary diseases, neurological diseases, liver diseases, metabolic diseases, autoimmune diseases, cardiovascular diseases, and numerous other chronic diseases. Multiple studies have indicated the safety and efficacy of curcumin in numerous animals including rodents, monkeys, horses, rabbits, and cats and have provided a solid basis for evaluating its safety and efficacy in humans. To date, more than 65 human clinical trials of curcumin, which included more than 1000 patients, have been completed, and as many as 35 clinical trials are underway. Curcumin is now used as a supplement in several countries including the United States, India, Japan, Korea, Thailand, China, Turkey, South Africa, Nepal, and Pakistan. In this review, we provide evidence for the pharmaceutical uses of curcumin for various diseases. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.","title":"Curcumin, a component of turmeric: from farm to pharmacy."},{"docid":"MED-2802","text":"OBJECTIVE: The objective of this study was to determine the efficacy and safety of Curcuma domestica extracts in pain reduction and functional improvement in patients with knee osteoarthritis. STUDY DESIGN AND SETTING: The design and setting were a randomized controlled study at a university hospital in Bangkok, Thailand. METHODS: One-hundred and seven (107) patients with primary knee osteoarthritis (OA) with pain score of > or =5 were randomized to receive ibuprofen 800 mg per day or C. domestica extracts 2 g per day for 6 weeks. The main outcomes were improvement in pain on level walking, pain on stairs, and functions of knee assessed by time spent during 100-m walk and going up and down a flight of stairs. The adverse events were also recorded. RESULTS: Fifty-two (52) and 55 patients were randomized to C. domestica extracts and ibuprofen groups, respectively. Baseline characteristics of the patients in both groups were not different. The mean scores of the aforementioned outcomes at weeks 0, 2, 4, and 6 were significantly improved when compared with the baseline values in both groups. There was no difference in those parameters between the patients receiving ibuprofen and C. domestica extracts, except pain on stairs (p = 0.016). No significant difference of adverse events between both groups was found (33.3% versus 44.2%, p = 0.36 in C. domestica extracts and ibuprofen groups, respectively). CONCLUSIONS: C. domestica extracts seem to be similarly efficacious and safe as ibuprofen for the treatment of knee OA.","title":"Efficacy and safety of Curcuma domestica extracts in patients with knee osteoarthritis."},{"docid":"MED-2813","text":"The use of turmeric, derived from the root of the plant Curcuma longa, for treatment of different inflammatory diseases has been described in Ayurveda and in traditional Chinese medicine for thousands of years. The active component of turmeric responsible for this activity, curcumin, was identified almost two centuries ago. Modern science has revealed that curcumin mediates its effects by modulation of several important molecular targets, including transcription factors (e.g., NF-kappaB, AP-1, Egr-1, beta-catenin, and PPAR-gamma), enzymes (e.g., COX2, 5-LOX, iNOS, and hemeoxygenase-1), cell cycle proteins (e.g., cyclin D1 and p21), cytokines (e.g., TNF, IL-1, IL-6, and chemokines), receptors (e.g., EGFR and HER2), and cell surface adhesion molecules. Because it can modulate the expression of these targets, curcumin is now being used to treat cancer, arthritis, diabetes, Crohn's disease, cardiovascular diseases, osteoporosis, Alzheimer's disease, psoriasis, and other pathologies. Interestingly, 6-gingerol, a natural analog of curcumin derived from the root of ginger (Zingiber officinalis), exhibits a biologic activity profile similar to that of curcumin. The efficacy, pharmacologic safety, and cost effectiveness of curcuminoids prompt us to \"get back to our roots.\"","title":"Curcumin: getting back to the roots."},{"docid":"MED-2583","text":"Inositol hexaphosphate (IP(6)), a naturally polyphosphorylated carbohydrate, has been reported to have significant in vivo and in vitro anticancer activity against numerous tumours, such as colon, prostate, breast, liver and rhabdomyosarcomas. To confirm this activity in haematological malignancies and to characterize some of the mechanisms of IP(6) action, we analysed its effects on human leukaemic cell lines and fresh chronic myelogenous leukaemia (CML) progenitor cells using a combined cellular and molecular approach. IP(6) had a dose-dependent cytotoxic effect on all of the evaluated cell lines, with accumulation in the G2M phase in two out of five cell lines tested. At the molecular level, cDNA microarray analysis after IP(6) exposure showed an extensive downmodulation of genes involved in transcription and cell cycle regulation and a coherent upregulation of cell cycle inhibitors. Furthermore, IP(6) treatment of fresh leukaemic samples of bone marrow CD34+ CML progenitor cells significantly inhibited granulocyte-macrophage colony-forming unit (CFU-GM) formation (P = 0.0062) in comparison to normal bone marrow specimens, which were not affected. No differentiating effect on HL60 cells was observed. Taken together, our results confirm the antiproliferative activity of IP(6) and suggest that it may have a specific antitumour effect also in chronic myeloid leukaemias, via active gene modulation.","title":"Effect of inositol hexaphosphate (IP(6)) on human normal and leukaemic haematopoietic cells."},{"docid":"MED-2786","text":"Alzheimer's disease (AD) is the most common form of dementia. There is limited choice in modern therapeutics, and drugs available have limited success with multiple side effects in addition to high cost. Hence, newer and alternate treatment options are being explored for effective and safer therapeutic targets to address AD. Turmeric possesses multiple medicinal uses including treatment for AD. Curcuminoids, a mixture of curcumin, demethoxycurcumin, and bisdemethoxycurcumin, are vital constituents of turmeric. It is generally believed that curcumin is the most important constituent of the curcuminoid mixture that contributes to the pharmacological profile of parent curcuminoid mixture or turmeric. A careful literature study reveals that the other two constituents of the curcuminoid mixture also contribute significantly to the effectiveness of curcuminoids in AD. Therefore, it is emphasized in this review that each component of the curcuminoid mixture plays a distinct role in making curcuminoid mixture useful in AD, and hence, the curcuminoid mixture represents turmeric in its medicinal value better than curcumin alone. The progress in understanding the disease etiology demands a multiple-site-targeted therapy, and the curcuminoid mixture of all components, each with different merits, makes this mixture more promising in combating the challenging disease. Copyright © 2013 John Wiley & Sons, Ltd.","title":"Therapeutic potential of turmeric in Alzheimer's disease: curcumin or curcuminoids?"},{"docid":"MED-2809","text":"Extensive research over the past half century has shown that curcumin (diferuloylmethane), a component of the golden spice turmeric (Curcuma longa), can modulate multiple cell signaling pathways. Extensive clinical trials over the past quarter century have addressed the pharmacokinetics, safety, and efficacy of this nutraceutical against numerous diseases in humans. Some promising effects have been observed in patients with various pro-inflammatory diseases including cancer, cardiovascular disease, arthritis, uveitis, ulcerative proctitis, Crohn’s disease, ulcerative colitis, irritable bowel disease, tropical pancreatitis, peptic ulcer, gastric ulcer, idiopathic orbital inflammatory pseudotumor, oral lichen planus, gastric inflammation, vitiligo, psoriasis, acute coronary syndrome, atherosclerosis, diabetes, diabetic nephropathy, diabetic microangiopathy, lupus nephritis, renal conditions, acquired immunodeficiency syndrome, β-thalassemia, biliary dyskinesia, Dejerine-Sottas disease, cholecystitis, and chronic bacterial prostatitis. Curcumin has also shown protection against hepatic conditions, chronic arsenic exposure, and alcohol intoxication. Dose-escalating studies have indicated the safety of curcumin at doses as high as 12 g/day over 3 months. Curcumin’s pleiotropic activities emanate from its ability to modulate numerous signaling molecules such as pro-inflammatory cytokines, apoptotic proteins, NF–κB, cyclooxygenase-2, 5-LOX, STAT3, C-reactive protein, prostaglandin E2, prostate-specific antigen, adhesion molecules, phosphorylase kinase, transforming growth factor-β, triglyceride, ET-1, creatinine, HO-1, AST, and ALT in human participants. In clinical trials, curcumin has been used either alone or in combination with other agents. Various formulations of curcumin, including nanoparticles, liposomal encapsulation, emulsions, capsules, tablets, and powder, have been examined. In this review, we discuss in detail the various human diseases in which the effect of curcumin has been investigated.","title":"Therapeutic Roles of Curcumin: Lessons Learned from Clinical Trials"},{"docid":"MED-4220","text":"OBJECTIVE: Accumulating evidence indicates that prostate cancer is associated with high levels of serum IGF-I. This study was conducted to determine whether a low-fat diet and exercise (DE) intervention may modulate the IGF axis and reduce prostate cancer cell growth in vitro. METHODS: Fasting serum was obtained from 14 men (age 60 +/- 3 years) participating in an 11-day DE program and from eight similarly aged men who had followed the DE program for 14.2 +/- 1.7 years (long-term). Insulin, IGF-I, IGFBP-1, and IGFBP-3 were measured by ELISA, and serum was used to stimulate LNCaP cell growth in vitro. RESULTS: Serum IGF-I levels decreased by 20% while IGFBP-1 increased by 53% after 11-day DE. In the long-term group, IGF-I was 55% lower, while IGFBP-1 was 150% higher relative to baseline. Serum insulin decreased by 25% after 11-day DE and was 68% lower in the long-term group, relative to baseline. No changes in serum IGFBP-3 were observed. Serum-stimulated LNCaP cell growth was reduced by 30% in post-11-day serum and by 44% in long-term serum relative to baseline. LNCaP cells incubated with post-DE serum showed increased apoptosis/ necrosis, compared to baseline. CONCLUSIONS: A low-fat diet and exercise intervention induces in-vivo changes in the circulating IGF axis and is associated with reduced growth and enhanced apoptosis/necrosis of LNCaP tumor cells in vitro.","title":"Effect of diet and exercise on serum insulin, IGF-I, and IGFBP-1 levels and growth of LNCaP cells in vitro (United States)."},{"docid":"MED-2822","text":"Curcumin is known to possess potent antiinflammatory and antiarthritic properties. This pilot clinical study evaluated the safety and effectiveness of curcumin alone, and in combination with diclofenac sodium in patients with active rheumatoid arthritis (RA). Forty-five patients diagnosed with RA were randomized into three groups with patients receiving curcumin (500 mg) and diclofenac sodium (50 mg) alone or their combination. The primary endpoints were reduction in Disease Activity Score (DAS) 28. The secondary endpoints included American College of Rheumatology (ACR) criteria for reduction in tenderness and swelling of joint scores. Patients in all three treatment groups showed statistically significant changes in their DAS scores. Interestingly, the curcumin group showed the highest percentage of improvement in overall DAS and ACR scores (ACR 20, 50 and 70) and these scores were significantly better than the patients in the diclofenac sodium group. More importantly, curcumin treatment was found to be safe and did not relate with any adverse events. Our study provides the first evidence for the safety and superiority of curcumin treatment in patients with active RA, and highlights the need for future large-scale trials to validate these findings in patients with RA and other arthritic conditions. Copyright © 2012 John Wiley & Sons, Ltd.","title":"A randomized, pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis."},{"docid":"MED-2793","text":"Piperine, a major active component of black and long peppers, has been reported to enhance drug bioavailability. The present studies were aimed at understanding the interaction of piperine with enzymatic drug biotransforming reactions in hepatic tissue in vitro and in vivo. Piperine inhibited arylhydrocarbon hydroxylation, ethylmorphine-N-demethylation, 7-ethoxycoumarin-O-deethylation and 3-hydroxy-benzo(a)pyrene glucuronidation in rat postmitochondrial supernatant in vitro in a dose-dependent manner. Piperine inhibition of these reactions in postmitochondrial supernatant from 3-methylcholanthrene- and phenobarbital-treated rats was similar to the controls. Inhibition by piperine of arylhydrocarbon hydroxylase (AHH) from 3-methylcholanthrene-treated rats was comparable to that observed with 7,8-benzoflavone. Piperine caused noncompetitive inhibition of hepatic microsomal AHH from the untreated and 3-methylcholanthrene-treated rats with a Ki of 30 microM which was close to the apparent Km of AHH observed in the controls. Similarly, the kinetics of inhibition of ethylmorphine-N-demethylase from control rat liver microsomes exhibited noncompetitive inhibition with an apparent Km of 0.8 mM and Ki of 35 microM. These studies demonstrated that piperine is a nonspecific inhibitor of drug metabolism which shows little discrimination between different cytochrome P-450 forms. Oral administration of piperine in rats strongly inhibited the hepatic AHH and UDP-glucuronyltransferase activities. The maximal inhibition of AHH observed within 1 hr restored to normal value in 6 hr. Pretreatment with piperine prolonged hexobarbital sleeping time and zoxazolamine paralysis time in mice at half the dose of SKF-525A. These results demonstrate that piperine is a potent inhibitor of drug metabolism.","title":"Biochemical basis of enhanced drug bioavailability by piperine: evidence that piperine is a potent inhibitor of drug metabolism."},{"docid":"MED-2601","text":"It has been reported that curcumin inhibited various types of cancer cells in vitro and in vivo. However, mechanisms of curcumin-inhibited cell growth and -induced apoptosis in human non-small cell lung cancer cells (NCI-H460) still remain unclear. In this study, NCI-H460 cells were treated with curcumin to determine its anticancer activity. Different concentrations of curcumin were used for different durations in NCI-H460 cells and the subsequent changes in the cell morphology, viability, cell cycle, mRNA and protein expressions were determined. Curcumin induced apoptotic morphologic changes in NCI-H460 cells in a dose-dependent manner. After curcumin treatment, BAX and BAD were up-regulated, BCL-2, BCL-X(L) and XIAP were down-regulated. In addition, reactive oxygen species (ROS), intracellular Ca(2+) and endoplasmic reticulum (ER) stress were increased in NCI-H460 cells after exposure to curcumin. These signals led to a loss of mitochondrial membrane potential (Delta Psi(m)) and culminated in caspase-3 activation. Curcumin-induced apoptosis was also stimulated through the FAS/caspase-8 (extrinsic) pathway and ER stress proteins, growth arrest- and DNA damage-inducible gene 153 (GADD153) and glucose-regulated protein 78 (GRP78) were activated in the NCI-H460 cells. Apoptotic cell death induced by curcumin was significantly reversed by pretreatment with ROS scavenger or caspase-8 inhibitor. Furthermore, the NCI-H460 cells tended to be arrested at the G(2)/M cell cycle stage after curcumin treatment and down-regulation of cyclin-dependent kinase 1 (CDK1) may be involved. In summary, curcumin exerts its anticancer effects on lung cancer NCI-H460 cells through apoptosis or cell cycle arrest.","title":"Curcumin induces apoptosis in human non-small cell lung cancer NCI-H460 cells through ER stress and caspase cascade- and mitochondria-dependent pat..."},{"docid":"MED-4543","text":"Phyllanthus emblica Linn. (PE) is a medicinal fruit used in many Asian traditional medicine systems for the treatment of various diseases including cancer. The present study tested the potential anticancer effects of aqueous extract of PE in four ways: (1) against cancer cell lines, (2) in vitro apoptosis, (3) mouse skin tumourigenesis and (4) in vitro invasiveness. The PE extract at 50-100 microg/mL significantly inhibited cell growth of six human cancer cell lines, A549 (lung), HepG2 (liver), HeLa (cervical), MDA-MB-231 (breast), SK-OV3 (ovarian) and SW620 (colorectal). However, the extract was not toxic against MRC5 (normal lung fibroblast). Apoptosis in HeLa cells was also observed as PE extract caused DNA fragmentation and increased activity of caspase-3/7 and caspase-8, but not caspase-9, and up-regulation of the Fas protein indicating a death receptor-mediated mechanism of apoptosis. Treatment of PE extract on mouse skin resulted in over 50% reduction of tumour numbers and volumes in animals treated with DMBA/TPA. Lastly, 25 and 50 microg/mL of PE extract inhibited invasiveness of MDA-MB-231 cells in the in vitro Matrigel invasion assay. These results suggest P. emblica exhibits anticancer activity against selected cancer cells, and warrants further study as a possible chemopreventive and antiinvasive agent. Copyright 2010 John Wiley & Sons, Ltd.","title":"Antitumour effects of Phyllanthus emblica L.: induction of cancer cell apoptosis and inhibition of in vivo tumour promotion and in vitro invasion o..."},{"docid":"MED-2585","text":"Inositol hexaphosphate (IP6) is a naturally occurring polyphosphorylated carbohydrate that is present in substantial amounts in almost all plant and mammalian cells. It was recently recognized to possess multiple biological functions. A striking anticancer effect of IP6 was demonstrated in different experimental models. Inositol is also a natural constituent possessing moderate anticancer activity. The most consistent and best anticancer results were obtained from the combination of IP6 plus inositol. In addition to reducing cell proliferation, IP6 increases differentiation of malignant cells, often resulting in a reversion to normal phenotype. Exogenously administered IP6 is rapidly taken into the cells and dephosphorylated to lower-phosphate inositol phosphates, which further interfere with signal transduction pathways and cell cycle arrest. Enhanced immunity and antioxidant properties can also contribute to tumor cell destruction. However, the molecular mechanisms underlying this anticancer action are not fully understood. Because it is abundantly present in regular diet, efficiently absorbed from the gastrointestinal tract, and safe, IP6 holds great promise in our strategies for the prevention and treatment of cancer. IP6 plus inositol enhances the anticancer effect of conventional chemotherapy, controls cancer metastases, and improves the quality of life, as shown in a pilot clinical trial. The data strongly argue for the use of IP6 plus inositol in our strategies for cancer prevention and treatment. However, the effectiveness and safety of IP6 plus inositol at therapeutic doses needs to be determined in phase I and phase II clinical trials in humans.","title":"Cancer inhibition by inositol hexaphosphate (IP6) and inositol: from laboratory to clinic."},{"docid":"MED-2572","text":"In traditional cultures, balancing health with a balanced lifestyle was a core belief. The diseases of modern civilization were rare. Indigenous people have patterns of illness very different from Western civilization; yet, they rapidly develop diseases once exposed to Western foods and lifestyles. Food and medicine were interwoven. All cultures used special or functional foods to prevent disease. Food could be used at different times either as food or medicine. Foods, cultivation, and cooking methods maximized community health and well-being. With methods passed down through generations, cooking processes were utilized that enhanced mineral and nutrient bioavailability. This article focuses on what researchers observed about the food traditions of indigenous people, their disease patterns, the use of specific foods, and the environmental factors that affect people who still eat traditional foods.","title":"Traditional non-Western diets."},{"docid":"MED-2820","text":"Scope The incidence of cancer is significantly lower in regions where turmeric is heavily consumed. Whether lower cancer incidence is due to turmeric was investigated by examining its effects on tumor cell proliferation, on pro-inflammatory transcription factors NF-κB and STAT3, and on associated gene products. Methods and results Cell proliferation and cell cytotoxicity were measured by the MTT method, NF-κB activity by EMSA, protein expression by Western blot analysis, ROS generation by FACS analysis, and osteoclastogenesis by TRAP assay. Turmeric inhibited NF-κB activation and down-regulated NF-κB-regulated gene products linked to survival (Bcl-2, cFLIP, XIAP, and cIAP1), proliferation (cyclin D1 and c-Myc), and metastasis (CXCR4) of cancer cells. The spice suppressed the activation of STAT3, and induced the death receptors (DR)4 and DR5. Turmeric enhanced the production of ROS, and suppressed the growth of tumor cell lines. Furthermore, turmeric sensitized the tumor cells to chemotherapeutic agents capecitabine and taxol. Turmeric was found to be more potent than pure curcumin for cell growth inhibition. Turmeric also inhibited NF-κB activation induced by RANKL that correlated with the suppression of osteoclastogenesis. Conclusion Our results indicate that turmeric can effectively block the proliferation of tumor cells through the suppression of NF-κB and STAT3 pathways.","title":"Turmeric (Curcuma longa) inhibits inflammatory nuclear factor (NF)-κB and NF-κB-regulated gene products and induces death receptors leading to suppressed proliferation, induced chemosensitization, and suppressed osteoclastogenesis"},{"docid":"MED-2787","text":"BACKGROUND: The extract of medicinal plants containing curcumin is traditionally believed to have a positive contraction effect on the human gall-bladder. AIMS: To compare the effect of 20 mg curcumin or placebo on the gall-bladder volume of healthy volunteers. METHODS: A randomized, double blind and crossover design study was carried out in 12 healthy volunteers (seven males and five females). Ultrasonography examination was carried out serially to measure the gall-bladder volume. The data obtained was analysed by paired Student's t-test. RESULTS: The fasting gall-bladder volumes of 15.74 +/- 4.29 mL on curcumin and 15.98 +/- 4.08 mL on placebo were similar (P > 0.20). The gall-bladder volume was reduced within the period after curcumin administration. The percentage of gall-bladder volume reduction at 0.5, 1.0, 1.5 and 2.0 h after 20 mg curcumin administration were 11.8 +/- 6.9, 16.8 +/- 7.4, 22.0 +/- 8.5 and 29. 3 +/- 8.3%, respectively, which was statistically significant compared to placebo. CONCLUSION: On the basis of the present findings, it appears that curcumin induces contraction of the human gall-bladder.","title":"The effect of curcumin and placebo on human gall-bladder function: an ultrasound study."},{"docid":"MED-2790","text":"Vasa (Adhatoda vasica Linn.) is a well known and easily available drug in almost all the seasons. Easy availability of any drug gains popularity among physicians as well as pharmaceuticals and this is the reason why almost every Kalpana of Vasa is found described in the Ayurvedika text. The different dosage forms of Vasa like Kvatha, Avaleha, Sneha, and Sandhana have been used for the treatment of Shwasa Roga. A number of research studies have been performed on different formulations of Vasa and its effect on Shwasa Roga. Therefore, a review study has been carried out on the Vasa extract, Vasa Avaleha (prepared from Svarasa and Kvatha), Vasa Ghrita, Vasarishta, and Vasakasava on Shwasa Roga, to know which formulation is better. It was found in the review that Vasa Ghana, Vasa Ghrita (1), and Vasa Avaleha have shown good results on Tamaka Shwasa.","title":"A clinical review of different formulations of Vasa (Adhatoda vasica) on Tamaka Shwasa (asthma)"},{"docid":"MED-2777","text":"BACKGROUND: Gout, an inflammatory arthritis, reportedly afflicts more than 2 million men and women in the United States. Previous reports have suggested an association between gout and kidney stone disease; however, these studies did not adjust for such important potential confounders as obesity and the presence of hypertension. To our knowledge, no published study has examined the independent association between gout and kidney stone disease. METHODS: We used a national probability sample of the US population to determine the independent association between reported gout and history of kidney stone disease. RESULTS: Among men and women 20 years and older, 5.6% (10 million) reported the previous passage of a kidney stone and 2.7% (5.1 million) reported a diagnosis of gout by a physician. Moreover, 8.6% of individuals who reported the passage of a kidney stone on two or more occasions had a history of gout. Conversely, the prevalence of previous kidney stones in subjects with reported gout was 13.9%. In the age-adjusted model, gout was associated with an increased odds ratio (OR) for previous kidney stones (OR, 1.97; 95% confidence interval [CI], 1.37 to 2.83). After further adjustment for sex, race, body mass index, and presence of hypertension, the OR for previous kidney stones in individuals with gout decreased to 1.49 (95% CI, 1.04 to 2.14). CONCLUSION: Showing an independent association between kidney stone disease and gout strongly suggests that they share common underlying pathophysiological mechanisms. Identification of these mechanisms may lead to improved preventive strategies for both conditions. Copyright 2002 by the National Kidney Foundation, Inc.","title":"The association between gout and nephrolithiasis: the National Health and Nutrition Examination Survey III, 1988-1994."},{"docid":"MED-4612","text":"Amino acids modulate the secretion of both insulin and glucagon; the composition of dietary protein therefore has the potential to influence the balance of glucagon and insulin activity. Soy protein, as well as many other vegan proteins, are higher in non-essential amino acids than most animal-derived food proteins, and as a result should preferentially favor glucagon production. Acting on hepatocytes, glucagon promotes (and insulin inhibits) cAMP-dependent mechanisms that down-regulate lipogenic enzymes and cholesterol synthesis, while up-regulating hepatic LDL receptors and production of the IGF-I antagonist IGFBP-1. The insulin-sensitizing properties of many vegan diets--high in fiber, low in saturated fat--should amplify these effects by down-regulating insulin secretion. Additionally, the relatively low essential amino acid content of some vegan diets may decrease hepatic IGF-I synthesis. Thus, diets featuring vegan proteins can be expected to lower elevated serum lipid levels, promote weight loss, and decrease circulating IGF-I activity. The latter effect should impede cancer induction (as is seen in animal studies with soy protein), lessen neutrophil-mediated inflammatory damage, and slow growth and maturation in children. In fact, vegans tend to have low serum lipids, lean physiques, shorter stature, later puberty, and decreased risk for certain prominent 'Western' cancers; a vegan diet has documented clinical efficacy in rheumatoid arthritis. Low-fat vegan diets may be especially protective in regard to cancers linked to insulin resistance--namely, breast and colon cancer--as well as prostate cancer; conversely, the high IGF-I activity associated with heavy ingestion of animal products may be largely responsible for the epidemic of 'Western' cancers in wealthy societies. Increased phytochemical intake is also likely to contribute to the reduction of cancer risk in vegans. Regression of coronary stenoses has been documented during low-fat vegan diets coupled with exercise training; such regimens also tend to markedly improve diabetic control and lower elevated blood pressure. Risk of many other degenerative disorders may be decreased in vegans, although reduced growth factor activity may be responsible for an increased risk of hemorrhagic stroke. By altering the glucagon/insulin balance, it is conceivable that supplemental intakes of key non-essential amino acids could enable omnivores to enjoy some of the health advantages of a vegan diet. An unnecessarily high intake of essential amino acids--either in the absolute sense or relative to total dietary protein--may prove to be as grave a risk factor for 'Western' degenerative diseases as is excessive fat intake.","title":"Vegan proteins may reduce risk of cancer, obesity, and cardiovascular disease by promoting increased glucagon activity."},{"docid":"MED-2831","text":"TNFs are major mediators of inflammation and inflammation-related diseases, hence, the United States Food and Drug Administration (FDA) has approved the use of blockers of the cytokine, TNF-α, for the treatment of osteoarthritis, inflammatory bowel disease, psoriasis and ankylosis. These drugs include the chimeric TNF antibody (infliximab), humanized TNF-α antibody (Humira) and soluble TNF receptor-II (Enbrel) and are associated with a total cumulative market value of more than $20 billion a year. As well as being expensive ($15 000–20 000 per person per year), these drugs have to be injected and have enough adverse effects to be given a black label warning by the FDA. In the current report, we describe an alternative, curcumin (diferuloylmethane), a component of turmeric (Curcuma longa) that is very inexpensive, orally bioavailable and highly safe in humans, yet can block TNF-α action and production in in vitro models, in animal models and in humans. In addition, we provide evidence for curcumin's activities against all of the diseases for which TNF blockers are currently being used. Mechanisms by which curcumin inhibits the production and the cell signalling pathways activated by this cytokine are also discussed. With health-care costs and safety being major issues today, this golden spice may help provide the solution. Linked Articles This article is part of a themed section on Emerging Therapeutic Aspects in Oncology. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.169.issue-8","title":"Curcumin: an orally bioavailable blocker of TNF and other pro-inflammatory biomarkers"},{"docid":"MED-2574","text":"Inositol hexaphosphate (IP(6)) is a naturally occurring polyphosphorylated carbohydrate, abundantly present in many plant sources and in certain high-fiber diets, such as cereals and legumes. In addition to being found in plants, IP(6) is contained in almost all mammalian cells, although in much smaller amounts, where it is important in regulating vital cellular functions such as signal transduction, cell proliferation, and differentiation. For a long time IP(6) has been recognized as a natural antioxidant. Recently IP(6) has received much attention for its role in cancer prevention and control of experimental tumor growth, progression, and metastasis. In addition, IP(6) possesses other significant benefits for human health, such as the ability to enhance immune system, prevent pathological calcification and kidney stone formation, lower elevated serum cholesterol, and reduce pathological platelet activity. In this review we show the efficacy and discuss some of the molecular mechanisms that govern the action of this dietary agent. Exogenously administered IP(6) is rapidly taken up into cells and dephosphorylated to lower inositol phosphates, which further affect signal transduction pathways resulting in cell cycle arrest. A striking anticancer action of IP(6) was demonstrated in different experimental models. In addition to reducing cell proliferation, IP(6) also induces differentiation of malignant cells. Enhanced immunity and antioxidant properties also contribute to tumor cell destruction. Preliminary studies in humans show that IP(6) and inositol, the precursor molecule of IP(6), appear to enhance the anticancer effect of conventional chemotherapy, control cancer metastases, and improve quality of life. Because it is abundantly present in regular diet, efficiently absorbed from the gastrointestinal tract, and safe, IP(6) + inositol holds great promise in our strategies for cancer prevention and therapy. There is clearly enough evidence to justify the initiation of full-scale clinical trials in humans.","title":"Protection against cancer by dietary IP6 and inositol."},{"docid":"MED-4114","text":"Induced apoptosis of autoreactive T-lymphocyte precursors in the thymus is crucial for the prevention of autoimmune disorders. IGF-I and prolactin, which are lymphocyte growth factors, may have the potential to suppress apoptosis in thymocytes and thus encourage autoimmunity; conversely, dietary fish oil rich in omega-3 fats appears to upregulate apoptosis in lymphocytes. Since whole-food vegan diets may downregulate systemic IGF-I activity, it is proposed that such a diet, in conjunction with fish oil supplementation and treatment with dopamine agonists capable of suppressing prolactin secretion, may have utility for treating and preventing autoimmune disorders. This prediction is consistent with the extreme rarity of autoimmune disorders among sub-Saharan black Africans as long as they followed their traditional quasi-vegan lifestyles, and with recent ecologic studies correlating risks for IDDM and for multiple sclerosis mortality with animal product and/or saturated fat consumption. Moreover, there is evidence that vegan or quasi-vegan diets are useful in the management of rheumatoid arthritis, multiple sclerosis, and possibly SLE. The dopamine agonist bromocryptine exerts anti-inflammatory effects in rodent models of autoimmunity, and there is preliminary evidence that this drug may be clinically useful in several human autoimmune diseases; better tolerated D2-specific agonists such as cabergoline may prove to be more practical for use in therapy. The moderate clinical utility of supplemental fish oil in rheumatoid arthritis and certain other autoimmune disorders is documented. It is not unlikely that extra-thymic anti-inflammatory effects contribute importantly to the clinical utility of vegan diets, bromocryptine, and fish oil in autoimmunity. The favorable impact of low latitude or high altitude on autoimmune risk may be mediated by superior vitamin D status, which is associated with decreased secretion of parathyroid hormone; there are theoretical grounds for suspecting that parathyroid hormone may inhibit apoptosis in thymocytes. Androgens appear to up-regulate thymocyte apoptosis, may be largely responsible for the relative protection from autoimmunity enjoyed by men, and merit further evaluation for the management of autoimmunity in women. It will probably prove more practical to prevent autoimmune disorders than to reverse them once established; a whole-food vegan diet, coupled with fish oil and vitamin D supplementation, may represent a practical strategy for achieving this prevention, while concurrently lowering risk for many other life-threatening 'Western' diseases. Copyright 2001 Harcourt Publishers Ltd.","title":"Upregulation of lymphocyte apoptosis as a strategy for preventing and treating autoimmune disorders: a role for whole-food vegan diets, fish oil an..."},{"docid":"MED-2816","text":"Plants contain numerous polyphenols, which have been shown to reduce inflammation and hereby to increase resistance to disease. Examples of such polyphenols are isothiocyanates in cabbage and broccoli, epigallocatechin in green tee, capsaicin in chili peppers, chalones, rutin and naringenin in apples, resveratrol in red wine and fresh peanuts and curcumin/curcuminoids in turmeric. Most diseases are maintained by a sustained discreet but obvious increased systemic inflammation. Many studies suggest that the effect of treatment can be improved by a combination of restriction in intake of proinflammatory molecules such as advanced glycation end products (AGE), advanced lipoperoxidation end products (ALE), and rich supply of antiinflammatory molecules such as plant polyphenols. To the polyphenols with a bulk of experimental documentation belong the curcuminoid family and especially its main ingredient, curcumin. This review summarizes the present knowledge about these turmericderived ingredients, which have proven to be strong antioxidants and inhibitors of cyclooxigenase-2 (COX-2), lipoxygenase (LOX) and nuclear factor kappa B (NF-kappaB) but also AGE. A plethora of clinical effects are reported in various experimental diseases, but clinical studies in humans are few. It is suggested that supply of polyphenols and particularly curcuminoids might be value as complement to pharmaceutical treatment, but also prebiotic treatment, in conditions proven to be rather therapy-resistant such as Crohn's, long-stayed patients in intensive care units, but also in conditions such as cancer, liver cirrhosis, chronic renal disease, chronic obstructive lung disease, diabetes and Alzheimer's disease.","title":"Plant-derived health: the effects of turmeric and curcuminoids."},{"docid":"MED-2780","text":"Spices, such as cinnamon, cloves, cardamom, garlic, ginger, cumin, coriander and turmeric are used all over the world as flavouring and colouring ingredients in Indian foods. Previous studies have shown that spices contain variable amounts of total oxalates but there are few reports of soluble oxalate contents. In this study, the total, soluble and insoluble oxalate contents of ten different spices commonly used in Indian cuisine were measured. Total oxalate content ranged from 194 (nutmeg) to 4,014 (green cardamom) mg/100 g DM, while the soluble oxalate contents ranged from 41 (nutmeg) to 3,977 (green cardamom) mg/100 g DM. Overall, the percentage of soluble oxalate content of the spices ranged from 4.7 to 99.1% of the total oxalate content which suggests that some spices present no risk to people liable to kidney stone formation, while other spices can supply significant amounts of soluble oxalates and therefore should be used in moderation.","title":"Total and soluble oxalate content of some Indian spices."},{"docid":"MED-2800","text":"The management of osteoarthritis represents a real challenge. This complex and multi-factorial disease evolves over decades and requires not only the alleviation of symptoms, i.e. pain and joint function but also the preservation of articular structure without side effects. Nutraceuticals are good candidates for the management of OA due to their safety profile and potential efficacy. However, they are not part of the treatment guidelines and published recommendations. Curcumin is the yellow pigment isolated from the rhizomes of Curcuma longa, commonly known as turmeric. Curcumin is a highly pleiotropic molecule with an excellent safety profile. Strong molecular evidence has been published for its potency to target multiple inflammatory diseases. However, naturally occurring curcumin cannot achieve its optimum therapeutic outcomes due to its low solubility and poor bioavailability. Nevertheless, curcumin presents great potential for treating OA and has been categorized as having preclinical evidence of efficacy. This review aimed at gathering most of the available information to document the potential efficacy of curcumin based on the results obtained in in vitro models of cartilage and osteoarthritis and in other diseases.","title":"Curcumin: a new paradigm and therapeutic opportunity for the treatment of osteoarthritis: curcumin for osteoarthritis management"},{"docid":"MED-2582","text":"Nonstarch polysaccharide (NSP) intake was measured in representative samples of 30 men aged 50-59 in 2 urban and 2 rural Scandinavian populations that exhibited a 3-4 fold difference in incidence of large bowel cancer. Intake was measured by chemical analysis of complete duplicate portions of all food eaten over one day by each individual. NSP intakes showed a rural-urban gradient, with 18.4 +/- 7.8 g/day in rural Finland and 18.0 +/- 6.4 g/day in rural Denmark versus 14.5 +/- 5.4 g/day in urban Finland and 13.2 +/- 4.8 g/day in urban Denmark. NSP intakes were also calculated (using food tables) from weighed food records kept over 4 days, one of which was the day on which the duplicate collection was made. Intakes were 2-2.5 g/day higher with this method than with direct chemical analysis, mainly because published tables of values have become outdated and inaccurate as a result of improved methods for measuring NSP in food. Individual variation from day to day in NSP intake was considerable. Average NSP intake and intake of some of its component sugars were inversely related to colon cancer incidence in this geographical comparison. To show a relationship at the individual level between diet and cancer risk in a prospective study would require detailed and accurate methods for the assessment of NSP consumption.","title":"Nonstarch polysaccharide consumption in four Scandinavian populations."},{"docid":"MED-2782","text":"BACKGROUND & AIMS: Curcumin is a biologically active phytochemical substance present in turmeric and has pharmacologic actions that might benefit patients with ulcerative colitis (UC). The aim in this trial was to assess the efficacy of curcumin as maintenance therapy in patients with quiescent ulcerative colitis (UC). METHODS: Eighty-nine patients with quiescent UC were recruited for this randomized, double-blind, multicenter trial of curcumin in the prevention of relapse. Forty-five patients received curcumin, 1g after breakfast and 1g after the evening meal, plus sulfasalazine (SZ) or mesalamine, and 44 patients received placebo plus SZ or mesalamine for 6 months. Clinical activity index (CAI) and endoscopic index (EI) were determined at entry, every 2 months (CAI), at the conclusion of 6-month trial, and at the end of 6-month follow-up. RESULTS: Seven patients were protocol violators. Of 43 patients who received curcumin, 2 relapsed during 6 months of therapy (4.65%), whereas 8 of 39 patients (20.51%) in the placebo group relapsed (P=.040). Recurrence rates evaluated on the basis of intention to treat showed significant difference between curcumin and placebo (P=.049). Furthermore, curcumin improved both CAI (P=.038) and EI (P=.0001), thus suppressing the morbidity associated with UC. A 6-month follow-up was done during which patients in both groups were on SZ or mesalamine. Eight additional patients in the curcumin group and 6 patients in the placebo group relapsed. CONCLUSIONS: Curcumin seems to be a promising and safe medication for maintaining remission in patients with quiescent UC. Further studies on curcumin should strengthen our findings.","title":"Curcumin maintenance therapy for ulcerative colitis: randomized, multicenter, double-blind, placebo-controlled trial."},{"docid":"MED-2785","text":"Curcumin is extensively used as a spice and pigment and has anticarcinogenic effects that could be linked to its antioxidant properties. However, some studies suggest that this natural compound possesses both pro- and antioxidative effects. In this study, we found that curcumin induced DNA damage to both the mitochondrial and nuclear genomes in human hepatoma G2 cells. Using quantitative polymerase chain reaction and immunocytochemistry staining of 8-hydroxydeoxyguanosine, we demonstrated that curcumin induced dose-dependent damage in both the mitochondrial and nuclear genomes and that the mitochondrial damage was more extensive. Nuclear DNA fragments were also evident in comet assays. The mechanism underlies the elevated level of reactive oxygen species and lipid peroxidation generated by curcumin. The lack of DNA damage at low doses suggested that low levels of curcumin does not induce DNA damage and may play an antioxidant role in carcinogenesis. But at high doses, we found that curcumin imposed oxidative stress and damaged DNA. These data reinforce the hypothesis that curcumin plays a conflicting dual role in carcinogenesis. Also, the extensive mitochondrial DNA damage might be an initial event triggering curcumin-induced cell death.","title":"Mitochondrial and nuclear DNA damage induced by curcumin in human hepatoma G2 cells."},{"docid":"MED-2559","text":"Inositol hexaphosphate (IP6) has anti-cancer properties, but recently other extracellular functions have been observed for IP6, including enhancing superoxide production and phagocytosis by neutrophils in the presence of microbial stimuli. This study investigated other inflammatory functions of IP6 on adherent neutrophils. The effect of IP6 on the release of IL-8, tumour necrosis factor (TNF-alpha) and IL-6 by neutrophils attached to either plastic or laminin for up to 6 hours in response to stimulation with lipopolysaccharide or N-formyl-Met-Leu-Phe (fMLP) was investigated. An increase in IL-8 secretion by stimulated cells occurred in the presence of IP6. The incubation of cells attached to laminin with IP6 alone (100-250 BM) did not effect cell morphology, but in the presence of 10(-7) M fMLP altered cell shape. A direct effect of IP6 on cell function was to trigger a sustained assembly of F-actin. Thus, exposure of neutrophils to low levels of IP6 appears to modulate selective neutrophil functions.","title":"Effect of IP6 on human neutrophil cytokine production and cell morphology."},{"docid":"MED-2568","text":"Inositol hexaphosphate (InsP6 or IP6) is ubiquitous. At 10 microM to 1 mM concentrations, IP6 and its lower phosphorylated forms (IP(1-5)) as well as inositol (Ins) are contained in most mammalian cells, wherein they are important in regulating vital cellular functions such as signal transduction, cell proliferation and differentiation. A striking anti-cancer action of IP6 has been demonstrated both in vivo and in vitro, which is based on the hypotheses that exogenously administered IP6 may be internalized, dephosphorylated to IP(1-5), and inhibit cell growth. There is additional evidence that Ins alone may further enhance the anti-cancer effect of IP6. Besides decreasing cellular proliferation, IP6 also causes differentiation of malignant cells often resulting in a reversion to normal phenotype. These data strongly point towards the involvement of signal transduction pathways, cell cycle regulatory genes, differentiation genes, oncogenes and perhaps, tumor suppressor genes in bringing about the observed anti-neoplastic action of IP6.","title":"IP6: a novel anti-cancer agent."},{"docid":"MED-2575","text":"Introduction Matrix metalloproteinases (MMPs) have repeatedly been shown to play a very active role in extracellular matrix degradation associated with tumor invasion and metastasis. Tissue inhibitors of MMPs (TIMPs) are well-known for their ability to inhibit MMP activity thereby inhibiting malignant progression. Inositol hexaphosphate (IP6 phytic acid) has been recognized to have both preventive and therapeutic effects against various cancers including that of colon. In in vitro studies, IP6 has been demonstrated to inhibit cancer cell adhesion and migration. In the present study, the effect of IP6 on the expression of MMP and TIMP genes was evaluated in unstimulated and IL-1β-stimulated colon cancer cell line Caco-2. Materials and methods Real-time QRT-PCR was used to validate the transcription level of selected MMP and TIMP genes in Caco-2 cells after treatment with 1 ng/ml of IL-1β, 2.5 mM of IP6, and both for 6, 12, and 24 h. Results Stimulation of cells with IL-1β only resulted in an overexpression of MMP and their TIMP mRNAs. A significant decrease in MMP-13, MMP-3, MMP-2, and TIMP-1 basal expression was achieved by IP6. IP6 was also an efficient downregulator of MMP-1, MMP-9, and TIMP-2 genes transcription stimulated by IL-1β in 6 h lasting culture. After 12 h, IL-1β-induced MMP-2 mRNA expression was significantly reduced by IP6. Conclusion Proinflammatory cytokine IL-1β upregulates MMP and TIMP mRNAs expression in colon cancer epithelial cells Caco-2. IP6 (2.5 mM) influences constitutive expression of both MMP and TIMP genes and downregulates IL-1β stimulated transcription of some of these genes. IP6 exerts its anti-metastatic activity through modulation of MMP and TIMP genes expression to prevent cancer cell migration and invasion.","title":"The effect of inositol hexaphosphate on the expression of selected metalloproteinases and their tissue inhibitors in IL-1β-stimulated colon cancer cells"},{"docid":"MED-2791","text":"Curcumin, a polyphenolic compound derived from dietary spice turmeric, possesses diverse pharmacologic effects including anti-inflammatory, antioxidant, antiproliferative and antiangiogenic activities. Phase I clinical trials have shown that curcumin is safe even at high doses (12 g/day) in humans but exhibit poor bioavailability. Major reasons contributing to the low plasma and tissue levels of curcumin appear to be due to poor absorption, rapid metabolism, and rapid systemic elimination. To improve the bioavailability of curcumin, numerous approaches have been undertaken. These approaches involve, first, the use of adjuvant like piperine that interferes with glucuronidation; second, the use of liposomal curcumin; third, curcumin nanoparticles; fourth, the use of curcumin phospholipid complex; and fifth, the use of structural analogues of curcumin (e.g., EF-24). The latter has been reported to have a rapid absorption with a peak plasma half-life. Despite the lower bioavailability, therapeutic efficacy of curcumin against various human diseases, including cancer, cardiovascular diseases, diabetes, arthritis, neurological diseases and Crohn's disease, has been documented. Enhanced bioavailability of curcumin in the near future is likely to bring this promising natural product to the forefront of therapeutic agents for treatment of human disease.","title":"Bioavailability of curcumin: problems and promises."},{"docid":"MED-2807","text":"In a previous three-month study of Meriva, a proprietary curcumin-phosphatidylcholine phytosome complex, decreased joint pain and improvement in joint function were observed in 50 osteoarthritis (OA) patients. Since OA is a chronic condition requiring prolonged treatment, the long-term efficacy and safety of Meriva were investigated in a longer (eight months) study involving 100 OA patients. The clinical end points (Western Ontario and McMaster Universities [WOMAC] score, Karnofsky Performance Scale Index, and treadmill walking performance) were complemented by the evaluation of a series of inflammatory markers (interleukin [IL]-1beta, IL-6, soluble CD40 ligand [sCD40L], soluble vascular cell adhesion molecule (sVCAM)-1, and erythrocyte sedimentation rate [ESR]). This represents the most ambitious attempt, to date, to evaluate the clinical efficacy and safety of curcumin as an anti-inflammatory agent. Significant improvements of both the clinical and biochemical end points were observed for Meriva compared to the control group. This, coupled with an excellent tolerability, suggests that Meriva is worth considering for the long-term complementary management of osteoarthritis.","title":"Efficacy and safety of Meriva®, a curcumin-phosphatidylcholine complex, during extended administration in osteoarthritis patients."},{"docid":"MED-2578","text":"The incidence of colonic cancer differs widely between various human populations. It has been suggested that dietary fiber content is of utmost importance and is inversely related to the occurrence of colonic cancer. However, high-fiber diets are not always correlated with low frequency of colonic cancer, suggesting the involvement of additional dietary constituents. Inositol hexaphosphate (phytic acid) is an abundant plant seed component present in many, but not all, fiber-rich diets. The authors have found that phytic acid is a potent inhibitor of iron-mediated generation of the hazardous oxidant, hydroxyl radical. Herein, the authors propose that inhibition of intracolonic hydroxyl radical generation, via the chelation of reactive iron by phytic acid, may help explain the suppression of colonic carcinogenesis and other inflammatory bowel diseases by diets rich in phytic acid.","title":"Dietary suppression of colonic cancer. Fiber or phytate?"},{"docid":"MED-2804","text":"Osteoarthritis (OA) is the most common form of arthritis in the US, and a leading cause of disability. It is typically defined in epidemiologic studies on the basis of radiographic findings and consideration of symptoms. Its incidence and prevalence are rising, likely related to the aging of the population and increasing obesity. Risk factors for OA include a number of person-level factors, such as age, sex, obesity, and genetics, as well as joint-specific factors that are likely reflective of abnormal loading of the joints. A number of methodologic challenges exist in studying OA that can hamper our ability to identify pertinent relationships.","title":"Epidemiology of OA"},{"docid":"MED-2797","text":"Osteoarthritis (OA) has long been considered a \"wear and tear\" disease leading to loss of cartilage. OA used to be considered the sole consequence of any process leading to increased pressure on one particular joint or fragility of cartilage matrix. Progress in molecular biology in the 1990s has profoundly modified this paradigm. The discovery that many soluble mediators such as cytokines or prostaglandins can increase the production of matrix metalloproteinases by chondrocytes led to the first steps of an \"inflammatory\" theory. However, it took a decade before synovitis was accepted as a critical feature of OA, and some studies are now opening the way to consider the condition a driver of the OA process. Recent experimental data have shown that subchondral bone may have a substantial role in the OA process, as a mechanical damper, as well as a source of inflammatory mediators implicated in the OA pain process and in the degradation of the deep layer of cartilage. Thus, initially considered cartilage driven, OA is a much more complex disease with inflammatory mediators released by cartilage, bone and synovium. Low-grade inflammation induced by the metabolic syndrome, innate immunity and inflammaging are some of the more recent arguments in favor of the inflammatory theory of OA and highlighted in this review. Copyright © 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.","title":"Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!)."},{"docid":"MED-2788","text":"Turmeric root has been used medicinally in China and India for thousands of years. The active components are thought to be the curcuminoids, primarily curcumin, which is commonly available worldwide as a standardized extract. This article reviews the pharmacology of curcuminoids, their use and efficacy, potential adverse effects, and dosage and standardization. Preclinical studies point to mechanisms of action that are predominantly anti-inflammatory and antineoplastic, while early human clinical trials suggest beneficial effects for dyspepsia, peptic ulcer, inflammatory bowel disease, rheumatoid arthritis, osteoarthritis, uveitis, orbital pseudotumor, and pancreatic cancer. Curcumin is well-tolerated; the most common side effects are nausea and diarrhea. Theoretical interactions exist due to purported effects on metabolic enzymes and transport proteins, but clinical reports do not support any meaningful interactions. Nonetheless, caution, especially with chemotherapy agents, is advised. Late-phase clinical trials are still needed to confirm most beneficial effects.","title":"Clinical utility of curcumin extract."},{"docid":"MED-2602","text":"In this study, we investigated the molecular pathways targeted by curcumin during apoptosis of human melanoma cell lines. We found that curcumin caused cell death in eight melanoma cell lines, four with wild-type and four with mutant p53. We demonstrate that curcumin-induced apoptosis is both dose- and time-dependent. We found that curcumin did not induce p53, suggesting that curcumin activates other apoptosis pathways. Our data show that curcumin activates caspases-3 and -8 but not caspase-9, supporting the rationale that apoptosis occurs via a membrane-mediated mechanism. Both a caspase-8 and broad-based caspase inhibitor, but not a caspase-9 specific inhibitor, suppressed curcumin-induced cell death. To further support our hypothesis that curcumin induces activation of a death receptor pathway, we show that curcumin induces Fas receptor aggregation in a FasL-independent manner and that low-temperature incubation, previously shown to inhibit receptor aggregation, prevented curcumin-induced cell death. Moreover, we demonstrate that expression of dominant negative FADD significantly inhibited curcumin-induced cell death. In addition, our results indicate that curcumin also blocks the NF-kappaB cell survival pathway and suppresses the apoptotic inhibitor, XIAP. Since melanoma cells with mutant p53 are strongly resistant to conventional chemotherapy, curcumin may overcome the chemoresistance of these cells and provide potential new avenues for treatment.","title":"Curcumin induces apoptosis in human melanoma cells through a Fas receptor/caspase-8 pathway independent of p53."},{"docid":"MED-5341","text":"The present study investigated the effects of a diet and exercise intervention on known breast cancer (BCa) risk factors, including estrogen, obesity, insulin, and insulin-like growth factor-I (IGF-I), in overweight/obese, postmenopausal women. In addition, using the subjects' pre- and postintervention serum in vitro, serum-stimulated growth and apoptosis of three estrogen receptor-positive BCa cell lines were studied. The women where placed on a low-fat (10-15% kcal), high-fiber (30-40 g per 1,000 kcal/day) diet and attended daily exercise classes for 2 wk. Serum estradiol was reduced in the women on hormone treatment (HT; n = 28) as well as those not on HT (n = 10). Serum insulin and IGF-I were significantly reduced in all women, whereas IGF binding protein-1 was increased significantly. In vitro growth of the BCa cell lines was reduced by 6.6% for the MCF-7 cells, 9.9% for the ZR-75-1 cells, and 18.5% for the T-47D cells. Apoptosis was increased by 20% in the ZR-75-1 cells, 23% in the MCF-7 cells, and 30% in the T-47D cells (n = 12). These results show that a very-low-fat, high-fiber diet combined with daily exercise results in major reductions in risk factors for BCa while subjects remained overweight/obese. These in vivo serum changes slowed the growth and induced apoptosis in serum-stimulated BCa cell lines in vitro.","title":"Effects of a low-fat, high-fiber diet and exercise program on breast cancer risk factors in vivo and tumor cell growth and apoptosis in vitro."},{"docid":"MED-2579","text":"There are now extensive scientific data suggesting the potential role of dietary and non-dietary phytochemicals in the prevention and control of prostate cancer (PCA) growth and progression. PCA is a disease of elderly male populations with a relatively slower rate of growth and progression as compared to most other cancers and, therefore, is a candidate disease for preventive intervention. Overall, PCA growth and progression involve aberrant mitogenic and survival signaling and deregulated cell cycle progression, accompanied by gradual accumulation of genetic and epigenetic changes over a period of years. Several mechanisms, including overexpression of growth, survival and angiogenic factors and their receptors, together with a loss/decrease of tumor suppressor p53, retinoblastoma and cyclin-dependent kinase inhibitor, have been implicated in PCA growth and progression. Therefore, phytochemicals targeting these molecular events could have a promising role in PCA prevention and/or therapy. Inositol hexaphosphate (IP6) is a major constituent of most cereals, legumes, nuts, oil seeds and soybean. Taken orally as an over-the-counter dietary/nutrient supplement, and is recognised as offering several health benefits without any known toxicity. In vitro anticancer efficacy of IP6 has been observed in many human, mouse and rat prostate cancer cells. Completed studies also show that oral feeding of IP6 inhibits human PCA xenograft growth in nude mice without toxicity. In a recently completed pilot study, we observed similar preventive effects of IP6 on prostate tumorigenesis in the TRAMP model. Mechanistic studies indicate that IP6 targets mitogenic and survival signaling, as well as cell cycle progression, in PCA cells. IP6 is also shown to target molecular events associated with angiogenesis. Moreover, IP6 has pleiotropic molecular targets for its overall efficacy against PCA and, therefore, could be a suitable candidate agent for preventive intervention of this malignancy in humans.","title":"Prostate cancer and inositol hexaphosphate: efficacy and mechanisms."},{"docid":"MED-2570","text":"The functional properties, including antioxidant and chemopreventative capacities as well as the inhibitory effects on angiotensin-converting enzyme (ACE), α-glucosidase and pancreatic lipase, of three Australian-grown faba bean genotypes (Nura, Rossa and TF(Ic*As)*483/13) were investigated using an array of in vitro assays. Chromatograms of on-line post column derivatisation assay coupled with HPLC revealed the existence of active phenolics (hump) in the coloured genotypes, which was lacking in the white-coloured breeding line, TF(Ic*As)*483/13. Roasting reduced the phenolic content, and diminished antioxidant activity by 10-40 % as measured by the reagent-based assays (diphenylpicrylhydrazyl, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) and oxygen radical absorbance capacity) in all genotypes. Cell culture-based antioxidant activity assay (cellular antioxidant activity) showed an increase of activity in the coloured genotypes after roasting. Faba bean extracts demonstrated cellular protection ability against H₂O₂-induced DNA damage (assessed using RAW264.7 cells), and inhibited the proliferation of all human cancer cell lines (BL13, AGS, Hep G2 and HT-29) evaluated. However, the effect of faba bean extracts on the non-transformed human cells (CCD-18Co) was negligible. Flow cytometric analyses showed that faba bean extracts successfully induced apoptosis of HL-60 (acute promyelocytic leukaemia) cells. The faba bean extracts also exhibited ACE, α-glucosidase and pancreatic lipase inhibitory activities. Overall, extracts from Nura (buff-coloured) and Rossa (red-coloured) were comparable, while TF(Ic*As)*483/13 (white-coloured) contained the lowest phenolic content and exhibited the least antioxidant and enzyme inhibition activities. These results are important to promote the utilisation of faba beans in human diets for various health benefits.","title":"In vitro investigations of the potential health benefits of Australian-grown faba beans (Vicia faba L.): chemopreventative capacity and inhibitory ..."},{"docid":"MED-2817","text":"Curcumin (diferuloylmethane), a yellow coloring agent extracted from turmeric is also used as a remedy for the treatment and prevention of inflammatory diseases. Acute and chronic inflammation is a major factor in the progression of obesity, type II diabetes, arthritis, pancreatitis, cardiovascular, neurodegenerative and metabolic diseases, as well as certain types of cancer. Turmeric has a long history of use in Ayurvedic medicine for the treatment of inflammatory disorders. Recent studies on the efficacy and therapeutic applicability of turmeric have suggested that the active ingredient of tumeric is curcumin. Further, compelling evidence has shown that curcumin has the ability to inhibit inflammatory cell proliferation, invasion, and angiogenesis through multiple molecular targets and mechanisms of action. Curcumin is safe, non-toxic, and mediates its anti-inflammatory effects through the down-regulation of inflammatory transcription factors, cytokines, redox status, protein kinases, and enzymes that all promote inflammation. In addition, curcumin induces apoptosis through mitochondrial and receptor-mediated pathways, as well as activation of caspase cascades. In the current study, the anti-inflammatory effects of curcumin were evaluated relative to various chronic inflammatory diseases. Based on the available pharmacological data obtained from in vitro and in vivo research, as well as clinical trials, an opportunity exists to translate curcumin into clinics for the prevention of inflammatory diseases in the near future. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.","title":"Curcumin in inflammatory diseases."},{"docid":"MED-4113","text":"Clonal deletion is arguably the most important mechanism of eliminating self-reactive thymocytes from the T-cell repertoire. Recent work has identified new players in this process. On the thymocyte side, several molecules have been newly implicated in the pathway from initial T-cell receptor signaling through to the final result: gene transcription and thymocyte apoptosis. In addition, several proapoptotic molecules have been found to be necessary for the death of self-reactive thymocytes. On the antigen-presenting cell side, the expression of peripheral self-antigens, regulated at least in part by the autoimmune regulator (AIRE) protein, is crucial for complete elimination of autoreactive thymocytes. The importance of thymic peripheral antigen expression and clonal deletion to self-tolerance is demonstrated in the autoimmune diseases autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy and type-1 diabetes mellitus.","title":"Good riddance: Thymocyte clonal deletion prevents autoimmunity."},{"docid":"MED-2598","text":"Death receptors belong to the TNF receptor family and are characterised by an intracellular death domain that serves to recruit adapter proteins such as TRADD and FADD and cysteine proteases such as Caspase-8. Activation of Caspase-8 on the aggregated receptor leads to apoptosis. Triggering of death receptors is mediated through the binding of specific ligands of the TNF family, which are homotrimeric type-2 membrane proteins displaying three receptor binding sites. There are various means of modulating the activation of death receptors. The status of the ligand (membrane-bound vs. soluble) is critical in the activation of Fas and of TRAIL receptors. Cleavage of membrane-bound FasL to a soluble form (sFasL) does not affect its ability to bind to Fas but drastically decreases its cytotoxic activity. Conversely, cross-linking epitope-tagged sFasL with anti-tag antibodies to mimic membrane-bound ligand results in a 1000-fold increase in cytotoxicity. This suggests that more than three Fas molecules need to be aggregated to efficiently signal apoptosis. Death receptors can also be regulated by decoy receptors. The cytotoxic ligand TRAIL interacts with five receptors, only two of which (TRAIL-R1 and -R2) have a death domain. TRAIL-R3 is anchored to the membrane by a glycolipid and acts as a dominant negative inhibitor of TRAIL-mediated apoptosis when overexpressed on TRAIL-sensitive cells. Intracellular proteins interacting with the apoptotic pathway are potential modulators of death receptors. FLIP resembles Caspase-8 in structure but lacks protease activity. It interacts with both FADD and Caspase-8 to inhibits the apoptotic signal of death receptors and, at the same time, can activate other signalling pathways such as that leading to NF-kappa B activation.","title":"Apoptosis induced by death receptors."},{"docid":"MED-2803","text":"Osteoarthritis is a condition caused in part by injury, loss of cartilage structure and function, and an imbalance in inflammatory and anti-inflammatory pathways. It primarily affects the articular cartilage and subchondral bone of synovial joints and results in joint failure, leading to pain upon weight bearing including walking and standing. There is no cure for osteoarthritis, as it is very difficult to restore the cartilage once it is destroyed. The goals of treatment are to relieve pain, maintain or improve joint mobility, increase the strength of the joints and minimize the disabling effects of the disease. Recent studies have shown an association between dietary polyphenols and the prevention of osteoarthritis-related musculoskeletal inflammation. This review discusses the effects of commonly consumed polyphenols, including curcumin, epigallocatechin gallate and green tea extract, resveratrol, nobiletin and citrus fruits, pomegranate, as well as genistein and soy protein, on osteoarthritis with an emphasis on molecular antiosteoarthritic mechanisms. Copyright © 2012 Elsevier Inc. All rights reserved.","title":"Dietary polyphenols and mechanisms of osteoarthritis."},{"docid":"MED-2830","text":"OBJECTIVE: The aim of this work was to determine the bioavailability of herbs and spices after human consumption by measuring the ability to protect lymphocytes from an oxidative injury and by examining the impact on inflammatory biomarkers in activated THP-1 cells. METHODS: Ten to 12 subjects in each of 13 groups consumed a defined amount of herb or spice for 7 days. Blood was drawn from subjects before consumption and 1 hour after taking the final herb or spice capsules. Subject serum and various extractions of the herbs and spices were analyzed for antioxidant capacity by oxygen radical absorbance capacity (ORAC) analysis or by 1,1-diphenyl-2-picrylhydrzyl (DPPH). Subject peripheral blood mononuclear cells (PBMCs) in medium with10% autologous serum were incubated with hydrogen peroxide to induce DNA strand breaks. Subject serum was also used to treat activated THP-1 cells to determine relative quantities of 3 inflammatory cytokine (tumor necrosis factor-α [TNF-α], interleukin-1α [IL-1α], and IL-6) mRNAs. RESULTS: Herbs and spices that protected PBMCs against DNA strand breaks were paprika, rosemary, ginger, heat-treated turmeric, sage, and cumin. Paprika also appeared to protect cells from normal apoptotic processes. Of the 3 cytokine mRNAs studied (TNF-α, IL-1α, and IL-6), TNF-α was the most sensitive responder to oxidized LDL-treated macrophages. Clove, ginger, rosemary, and turmeric were able to significantly reduce oxidized LDL-induced expression of TNF-α. Serum from those consuming ginger reduced all three inflammatory biomarkers. Ginger, rosemary, and turmeric showed protective capacity by both oxidative protection and inflammation measures. CONCLUSIONS: DNA strand breaks and inflammatory biomarkers are a good functional measure of a food's bioavailability.","title":"Bioavailability of herbs and spices in humans as determined by ex vivo inflammatory suppression and DNA strand breaks."},{"docid":"MED-4319","text":"The article gives an overview of phytic acid in food and of its significance for human nutrition. It summarises phytate sources in foods and discusses problems of phytic acid/phytate contents of food tables. Data on phytic acid intake are evaluated and daily phytic acid intake depending on food habits is assessed. Degradation of phytate during gastro-intestinal passage is summarised, the mechanism of phytate interacting with minerals and trace elements in the gastro-intestinal chyme described and the pathway of inositol phosphate hydrolysis in the gut presented. The present knowledge of phytate absorption is summarised and discussed. Effects of phytate on mineral and trace element bioavailability are reported and phytate degradation during processing and storage is described. Beneficial activities of dietary phytate such as its effects on calcification and kidney stone formation and on lowering blood glucose and lipids are reported. The antioxidative property of phytic acid and its potentional anticancerogenic activities are briefly surveyed. Development of the analysis of phytic acid and other inositol phosphates is described, problems of inositol phosphate determination and detection discussed and the need for standardisation of phytic acid analysis in foods argued.","title":"Phytate in foods and significance for humans: food sources, intake, processing, bioavailability, protective role and analysis."},{"docid":"MED-2821","text":"The purpose of this review is to summarize the pertinent literature published in the present era regarding the antiulcerogenic property of curcumin against the pathological changes in response to ulcer effectors (Helicobacter pylori infection, chronic ingestion of non-steroidal anti-inflammatory drugs, and exogenous substances). The gastrointestinal problems caused by different etiologies was observed to be associated with the alterations of various physiologic parameters such as reactive oxygen species, nitric oxide synthase, lipid peroxidation, and secretion of excessive gastric acid. Gastrointestinal ulcer results probably due to imbalance between the aggressive and the defensive factors. In 80% of the cases, gastric ulcer is caused primarily due to the use of non-steroidal anti-inflammatory category of drug, 10% by H. pylori, and about 8-10% by the intake of very spicy and fast food. Although a number of antiulcer drugs and cytoprotectants are available, all these drugs have side effects and limitations. In the recent years a widespread search has been launched to identify new antiulcer drugs from synthetic and natural resources. An Indian dietary derivative (curcumin), a yellow pigment found in the rhizome of Curcuma longa, has been widely used for the treatment of several diseases. Epidemiologically, it was suggested that curcumin might reduce the risk of inflammatory disorders, such as cancer and ulcer. These biological effects are attributed to its anti-inflammatory and antioxidant activities. It can, therefore, be reported from the literature that curcumin PRevents gastrointestinal-induced ulcer and can be recommended as a novel drug for ulcer treatment.","title":"Turmeric (curcumin) remedies gastroprotective action"},{"docid":"MED-4112","text":"Co-stimulatory signals through the CD28 receptor enhance the survival of T cells that have their antigen receptor (TCR) engaged. Here we show that stimulation through the CD28 receptor in the absence of TCR engagement with either an anti-CD28 cross-linking antibody or the CD80 ligand transiently increases expression of the insulin-like growth factor-I receptor (IGF-IR) on T cells. Antibodies that block signaling through the IGF-IR decrease the survival of T cells activated through the TCR and CD28 in the presence of IL-2 by more than 50%, and also enhance susceptibility to Fas-induced apoptosis. CD28 stimulation increases IGF-IR expression on Jurkat cells, and exogenously added IGF-I can protect these cells from Fas-induced apoptosis. We conclude that CD28-mediated enhancement of IGF-IR expression provides activated T cells with essential survival signals that are independent of survival mediated by IL-2 and Bcl-xl.","title":"The insulin-like growth factor-I receptor is regulated by CD28 and protects activated T cells from apoptosis."},{"docid":"MED-2581","text":"A hospital-based case-control study of diet and colorectal cancer was conducted among Chinese in Singapore (who constitute 77% of the population). A total of 203 cases and 425 controls were included. A history of the usual dietary intake one year prior to interview was taken using a quantitative food frequency questionnaire. Daily intakes of nutrients and selected food items were computed and stratified by tertiles of the control range, to assess risk in low-, medium- and high-intake categories. Effects were adjusted in analysis for age, sex, Chinese dialect group and occupation. For cancers of colon and rectum combined, significant observations were a protective effect of high cruciferous vegetable intake (OR = 0.50, p less than 0.01) and a predisposing effect of a high meat/vegetable consumption ratio (OR = 1.77, p less than 0.05). Similar results were observed for colon cancer alone. For rectal cancer alone (only 71 cases), significant (p less than 0.05) protective effects were observed for high intakes of protein (OR = 0.61), fibre (OR = 0.46), beta-carotene (OR = 0.54), cruciferous vegetables (OR = 0.51) and total vegetables (OR = 0.51). When further assessed by multiple logistic regression, tests for trend and assessment of risk in the extreme highest and lowest quintiles of the control range, the factors consistently significant were cruciferous vegetable intake and the meat/vegetable ratio. A particularly high relative risk was also noted in association with low coffee consumption (OR = 1.59, with p less than 0.05 for trend). No consistent trends were noted for fat or fibre intakes. For non-dietary variables investigated, a history of cholecystectomy increased the risk of both cancers combined (OR = 3.43, p less than 0.05) and colon cancer alone (OR = 4.39, p less than 0.01). This study in an Asian population of countries of Southern and Eastern Asia newly undergoing industrialization and in which rapid economic change is reflected in changing cancer patterns, suggests that the protective effects of certain dietary constituents, notably the cruciferous vegetables, may be more important than the hitherto stressed carcinogenic potential of fat and protein.","title":"Colorectal cancer and diet in an Asian population--a case-control study among Singapore Chinese."},{"docid":"MED-2603","text":"FAS-associated protein with death domain (FADD) is the key adaptor protein transmitting apoptotic signals mediated by the main death receptors (DRs). Besides being an essential instrument in cell death, FADD is also implicated in proliferation, cell cycle progression, tumor development, inflammation, innate immunity, and autophagy. Recently, many of these new functions of FADD were shown to be independent of DRs. Moreover, FADD function is dictated by protein localization and phosphorylation state. Thus, FADD is a crucial and unique controller of many essential cellular processes. The full understanding of the networks dictating the ultimate function of FADD may provide a new paradigm for other multifaceted proteins. Copyright 2010 Elsevier Ltd. All rights reserved.","title":"FADD: a regulator of life and death."},{"docid":"MED-2808","text":"Chemotherapy remains the core of anticancer treatment. However, despite the tremendous strides made in the development of targeted anticancer therapies, emergence of resistance to chemotherapeutic drugs is still a major obstacle in the successful management of resistant tumours. Therefore, profound investigation into the in-depth molecular mechanisms of drug resistance is essential and may hopefully translate into effective therapies that can flip the switch from drug resistance to susceptibility. Mechanistically, resistance phenomena may be explained by (i) overexpression of drug efflux pumps, (ii) enhanced drug detoxification, (iii) rapid DNA repair efficiency, (iv) defects in apoptosis regulation, and (v) active cell survival signals. Several adverse effects associated with multidrug resistance and the need for safe multi-targeted anticancer drugs instigated the use of the phytochemical, curcumin, the yellow pigment of the spice turmeric, which has pleotropic activities. We performed a structured literature review using PubMed and Medline searches with secondary review of cited publications, identifying studies on the role of curcumin in conquering drug resistance in cancer. This review describes how curcumin sensitizes cancer cells through regulation of multiple multidrug resistance pathways, thus employing one drug for multiple targets. Curcumin helps the cancer cells to regain their 'forgotten' apoptosis, modulates drug-target interaction at different levels, restrains survival pathways when their proteins are overexpressed, and finds an alternate way to carry forward the process of sensitization of different resistant tumours. Additionally, the review dissects the role of curcumin, if any, in targeting the major culprit of drug resistance, cancer stem cells (CSC), thereby circumventing resistance. Taken together, this review strongly suggests that curcumin is a promising chemosensitizing agent and that the unique properties of curcumin may be exploited for successful management of resistant tumours.","title":"Death by design: where curcumin sensitizes drug-resistant tumours."},{"docid":"MED-4115","text":"Cui and associates show that healthy individuals have natural autoantibodies (NAAs) specific for myeloperoxidase, proteinase 3, and glomerular basement membrane (GBM) with the same specificity as anti-neutrophil cytoplasmic antibodies and anti-GBM antibodies that are pathogenic. Although Ehrlich proposed horror autotoxicus and Burnet envisioned elimination of forbidden clones, NAAs are present in all healthy individuals and play beneficial homeostatic roles. Pathogenic autoimmunity is dysregulation of natural homeostatic autoimmunity rather than onset of a previously absent self-recognition.","title":"The rise and fall of horror autotoxicus and forbidden clones."},{"docid":"MED-2580","text":"Adequate fruit and vegetable intake was suggested to protect against colorectal cancer and colorectal adenomas; however, several recent prospective studies reported no association. We examined the association between fruits and vegetables and adenomatous polyp recurrence in the Polyp Prevention Trial (PPT). The PPT was a low-fat, high-fiber, high-fruit, and vegetable dietary intervention trial of adenoma recurrence, in which there were no differences in the rate of adenoma recurrence in participants in the intervention and control arms of the trial. In this analysis of the entire PPT trial–based cohort, multiple logistic regression analysis was used to estimate the odds ratio (OR) of advanced and nonadvanced adenoma recurrence within quartiles of baseline and change (baseline minus the mean over 3 y) in fruit and vegetable intake, after adjustment for age, total energyy intake, use of nonsteroidal anti-inflammatory drugs, BMI, and gender. There were no significant associations between nonadvanced adenoma recurrence and overall change in fruit and vegetable consumption; however, those in the highest quartile of change in dry bean intake (greatest increase) compared with those in the lowest had a significantly reduced OR for advanced adenoma recurrence (OR = 0.35; 95% CI, 0.18–0.69; P for trend = 0.001). The median in the highest quartile of change in dry bean intake was 370% higher than the baseline intake. The PPT trial–based cohort provides evidence that dry beans may be inversely associated with advanced adenoma recurrence.","title":"High Dry Bean Intake and Reduced Risk of Advanced Colorectal Adenoma Recurrence among Participants in the Polyp Prevention Trial"},{"docid":"MED-2823","text":"Curcumin, the yellow pigment from the rhizoma of Curcuma longa, is a widely studied phytochemical which has a variety of biological activities: anti-inflammatory and anti-oxidative. In this review we discuss the biological mechanisms and possible clinical effects of curcumin treatment on cancer therapy, and neurodegenerative diseases such as Alzheimer's Disease, with particular attention to the cell death processes induced by curcumin. Since oxidative stress and inflammation are major determinants of the aging process, we also argue that curcumin can have a more general effect that slows down the rate of aging. Finally, the effects of curcumin can be described as xenohormetic, since it activates a sort of stress response in mammalian cells.","title":"Curcumin in Cell Death Processes: A Challenge for CAM of Age-Related Pathologies"},{"docid":"MED-2607","text":"Numerous natural compounds have been extensively investigated for their potential for cancer prevention over decades. Curcumin, from Curcuma longa, is a highly promising natural compound that can be potentially used for chemoprevention of multiple cancers. Curcumin modulates multiple molecular pathways involved in the lengthy carcinogenesis process to exert its chemopreventive effects through several mechanisms: promoting apoptosis, inhibiting survival signals, scavenging reactive oxidative species (ROS), and reducing the inflammatory cancer microenvironment. Curcumin fulfills the characteristics for an ideal chemopreventive agent with its low toxicity, affordability, and easy accessibility. Nevertheless, the clinical application of curcumin is currently compromised by its poor bioavailability. Here we review the potential of curcumin in cancer prevention, its molecular targets, and action mechanisms. Finally, we suggest specific recommendations to improve its efficacy and bioavailability for clinical applications.","title":"New perspectives of curcumin in cancer prevention"},{"docid":"MED-2799","text":"Objective: To compare selected immunohistological features of inflammation in synovial tissue from patients with early and late osteoarthritis (OA). Methods: Synovial tissue samples were obtained from 10 patients with knee pain, normal radiographs, and arthroscopic manifestations of OA (early OA), and from 15 patients with OA undergoing knee joint arthroplasty (late OA). Conventional immunohistochemical techniques were used to measure microscopic manifestations of inflammation. The inflammatory cell infiltrate, blood vessel formation, and angiogenic factors, NF-κB activation, expression of tumour necrosis factor α (TNFα) and interleukin 1ß (IL1ß), and the presence of cyclo-oxygenase (COX)-1 and COX-2 were quantified. Fibroblast-like synoviocytes (FLS) were isolated from early and late OA tissue samples to compare in vitro production of prostaglandin E2 (PGE2) Results: Synovial tissue from patients with early OA demonstrated significantly greater CD4+ (p = 0.017) and CD68+ (p<0.001) cell infiltration, blood vessel formation (p = 0.01), vascular endothelial growth factor (p = 0.001), and intercellular adhesion molecule-1 expression (p<0.001). Numbers of cells producing TNFα and IL1ß were also significantly greater in early OA (p<0.001). Manifestations of inflammation in early OA were associated with increased expression of the NF-κB1 (p<0.001) and RelA (p = 0.015) subunits, and with increased COX-2 expression (p = 0.04). Cytokine-induced PGE2 production by cultured FLS was similar in both groups. Conclusion: Increased mononuclear cell infiltration and overexpression of mediators of inflammation were seen in early OA, compared with late OA. Isolated FLS were functionally similar in both groups, consistent with microenvironmental differences in the synovial tissue during different phases of OA. These observations may have important therapeutic implications for some patients during the early evolution of OA.","title":"Synovial tissue inflammation in early and late osteoarthritis"},{"docid":"MED-2577","text":"A case-control study probing the role of diet on the incidence of colorectal cancer was undertaken in Athens, Greece, in a population characterized by ethnic homogeneity but substantial heterogeneity with respect to dietary habits. The case series consisted of 100 consecutive patients with histologically confirmed colorectal cancer admitted to two large hospitals of Athens during a 16-month period; the control series consisted of orthopaedic patients, admitted to the same hospitals during the same time period, individually matched to the index cases by age and sex. Dietary histories concerning the frequency of consumption (per month or per week) of about 80 food items were obtained by the same interviewer. Cases reported significantly less frequent consumption of vegetables (particularly beets, spinach, lettuce and cabbage) and, independently, significantly more frequent consumption of meat (notably lamb and beef). Between the two extremes (high-vegetable, low-meat diet versus high-meat, low-vegetable diet) a risk ratio of about 8 appears to exist, sufficient (in size and direction) to explain a substantial part of the international variation in the incidence of colorectal cancer. Significant associations were not found with beer or other alcoholic beverages, and significant interactions were not noted with respect to age, sex and anatomic localization (colon vs. rectum).","title":"Diet and colorectal cancer: a case-control study in Greece."},{"docid":"MED-2571","text":"Background Prospective, randomized, pilot clinical study was conducted to evaluate the beneficial effects of inositol hexaphosphate (IP6) + Inositol in breast cancer patients treated with adjuvant therapy. Patients and methods Patients with invasive ductal breast cancer where polychemotherapy was indicated were monitored in the period from 2005-2007. Fourteen patients in the same stage of ductal invasive breast cancer were involved in the study, divided in two randomized groups. One group was subjected to take IP6 + Inositol while the other group was taking placebo. In both groups of patients the same laboratory parameters were monitored. When the treatment was finished, all patients have filled questionnaires QLQ C30 and QLQ-BR23 to determine the quality of life. Results Patients receiving chemotherapy, along with IP6 + Inositol did not have cytopenia, drop in leukocyte and platelet counts. Red blood cell counts and tumor markers were unaltered in both groups. However, patients who took IP6 + Inositol had significantly better quality of life (p = 0.05) and functional status (p = 0.0003) and were able to perform their daily activities. Conclusion IP6 + Inositol as an adjunctive therapy is valuable help in ameliorating the side effects and preserving quality of life among the patients treated with chemotherapy.","title":"Efficacy of IP6 + inositol in the treatment of breast cancer patients receiving chemotherapy: prospective, randomized, pilot clinical study"},{"docid":"MED-2811","text":"Inflammatory bowel disease (IBD) comprising of ulcerative colitis (UC) and Crohn's disease (CD) is a major ailment affecting the small and large bowel. In clinics, IBD is treated using 5-amninosalicylates, antibiotics, the steroids and immunomodulators. Unfortunately, the long term usages of these agents are associated with undue side effects and compromise the therapeutic advantage. Accordingly, there is a need for novel agents that are effective, acceptable and non toxic to humans. Preclinical studies in experimental animals have shown that curcumin, an active principle of the Indian spice turmeric (Curcuma longa Linn) is effective in preventing or ameliorating UC and inflammation. Over the last few decades there has been increasing interest in the possible role of curcumin in IBD and several studies with various experimental models of IBD have shown it to be effective in mediating the inhibitory effects by scavenging free radicals, increasing antioxidants, influencing multiple signaling pathways, especially the kinases (MAPK, ERK), inhibiting myeloperoxidase, COX-1, COX-2, LOX, TNF-α, IFN-γ, iNOS; inhibiting the transcription factor NF-κB. Clinical studies have also shown that co-administration of curcumin with conventional drugs was effective, to be well-tolerated and treated as a safe medication for maintaining remission, to prevent relapse and improve clinical activity index. Large randomized controlled clinical investigations are required to fully understand the potential of oral curcumin for treating IBD.","title":"Curcumin, an active component of turmeric in the prevention and treatment of ulcerative colitis: preclinical and clinical observations."},{"docid":"MED-2818","text":"Curcumin is a polyphenol derived from the herbal remedy and dietary spice turmeric. It possesses diverse anti-inflammatory and anti-cancer properties following oral or topical administration. Apart from curcumin's potent antioxidant capacity at neutral and acidic pH, its mechanisms of action include inhibition of several cell signalling pathways at multiple levels, effects on cellular enzymes such as cyclooxygenase and glutathione S-transferases, immuno-modulation and effects on angiogenesis and cell-cell adhesion. Curcumin's ability to affect gene transcription and to induce apoptosis in preclinical models is likely to be of particular relevance to cancer chemoprevention and chemotherapy in patients. Although curcumin's low systemic bioavailability following oral dosing may limit access of sufficient concentrations for pharmacological effect in certain tissues, the attainment of biologically active levels in the gastrointestinal tract has been demonstrated in animals and humans. Sufficient data currently exist to advocate phase II clinical evaluation of oral curcumin in patients with invasive malignancy or pre-invasive lesions of the gastrointestinal tract, particularly the colon and rectum.","title":"Curcumin: the story so far."},{"docid":"MED-2792","text":"Two populations of immigrants to London and to the West Indies from the Indian subcontinent have higher than expected morbidity and mortality from atherosclerosis but do not show the commonly accepted major risk factors. This study investigated the hypothesis that ghee, a clarified butter product prized in Indian cooking, contains cholesterol oxides and could therefore be an important source of dietary exposure to cholesterol oxides and an explanation for the high atherosclerosis risk. Substantial amounts of cholesterol oxides were found in ghee (12.3% of sterols), but not in fresh butter, by thin-layer and high-performance-liquid chromatography. Dietary exposure to cholesterol oxides from ghee may offer a logical explanation for the high frequency of atherosclerotic complications in these Indian populations.","title":"Cholesterol oxides in Indian ghee: possible cause of unexplained high risk of atherosclerosis in Indian immigrant populations."},{"docid":"MED-4390","text":"The medicinal properties of curcumin obtained from Curcuma longa L. cannot be utilised because of poor bioavailability due to its rapid metabolism in the liver and intestinal wall. In this study, the effect of combining piperine, a known inhibitor of hepatic and intestinal glucuronidation, was evaluated on the bioavailability of curcumin in rats and healthy human volunteers. When curcumin was given alone, in the dose 2 g/kg to rats, moderate serum concentrations were achieved over a period of 4 h. Concomitant administration of piperine 20 mg/kg increased the serum concentration of curcumin for a short period of 1-2 h post drug. Time to maximum was significantly increased (P < 0.02) while elimination half life and clearance significantly decreased (P < 0.02), and the bioavailability was increased by 154%. On the other hand in humans after a dose of 2 g curcumin alone, serum levels were either undetectable or very low. Concomitant administration of piperine 20 mg produced much higher concentrations from 0.25 to 1 h post drug (P < 0.01 at 0.25 and 0.5 h; P < 0.001 at 1 h), the increase in bioavailability was 2000%. The study shows that in the dosages used, piperine enhances the serum concentration, extent of absorption and bioavailability of curcumin in both rats and humans with no adverse effects.","title":"Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers."},{"docid":"MED-2584","text":"In a 6-year prospective study, the authors examined the relation between diet and incident colon cancer among 32,051 non-Hispanic white cohort members of the Adventist Health Study (California, 1976-1982) who, at baseline, had no documented or reported history of cancer. The risk of colon cancer was determined from proportional hazards regression with adjustment for age and other covariates. The authors found a positive association with total meat intake (risk ratio (RR) for > or =1 time/week vs. no meat intake = 1.85, 95% confidence interval (CI) 1.19-2.87; p for trend = 0.01) and, among subjects who favored specific types of meat, positive associations with red meat intake (RR for > or =1 time/week vs. no red meat intake = 1.90, 95% CI 1.16-3.11; p for trend = 0.02) and white meat intake (RR for > or =1 time/week vs. no white meat intake = 3.29, 95% CI 1.60-6.75; p for trend = 0.006). An inverse association with legume intake (RR for >2 times/week vs. <1 time/week = 0.53, 95% CI 0.33-0.86; p for trend = 0.03) was observed. Among men, a positive association with body mass index was observed (relative to the RR for tertile III (>25.6 kg/m2) vs. tertile I (<22.5 kg/m2) = 2.63, 95% CI 1.12-6.13; p for trend = 0.05). A complex relation was identified whereby subjects exhibiting a high red meat intake, a low legume intake, and a high body mass experienced a more than threefold elevation in risk relative to all other patterns based on these variables. This pattern of putative risk factors would likely contribute to increases in both insulin resistance (high body mass, high red meat intake) and glycemic load (low legume intake), a synergism that, if causal, implicates hyperinsulinemic exposure in colon carcinogenesis. The overall findings from this cohort identify both red meat intake and white meat intake as important dietary risk factors for colon cancer and raise the possibility that the risk due to red meat intake reflects a more complex etiology.","title":"Dietary risk factors for colon cancer in a low-risk population."},{"docid":"MED-2824","text":"Cancer is primarily a disease of old age, and that life style plays a major role in the development of most cancers is now well recognized. While plant-based formulations have been used to treat cancer for centuries, current treatments usually involve poisonous mustard gas, chemotherapy, radiation, and targeted therapies. While traditional plant-derived medicines are safe, what are the active principles in them and how do they mediate their effects against cancer is perhaps best illustrated by curcumin, a derivative of turmeric used for centuries to treat a wide variety of inflammatory conditions. Curcumin is a diferuloylmethane derived from the Indian spice, turmeric (popularly called \"curry powder\") that has been shown to interfere with multiple cell signaling pathways, including cell cycle (cyclin D1 and cyclin E), apoptosis (activation of caspases and down-regulation of antiapoptotic gene products), proliferation (HER-2, EGFR, and AP-1), survival (PI3K/AKT pathway), invasion (MMP-9 and adhesion molecules), angiogenesis (VEGF), metastasis (CXCR-4) and inflammation (NF-kappaB, TNF, IL-6, IL-1, COX-2, and 5-LOX). The activity of curcumin reported against leukemia and lymphoma, gastrointestinal cancers, genitourinary cancers, breast cancer, ovarian cancer, head and neck squamous cell carcinoma, lung cancer, melanoma, neurological cancers, and sarcoma reflects its ability to affect multiple targets. Thus an \"old-age\" disease such as cancer requires an \"age-old\" treatment.","title":"Curcumin and cancer: an \"old-age\" disease with an \"age-old\" solution."},{"docid":"MED-2783","text":"Although much has been published about curcumin, which is obtained from turmeric, comparatively little is known about turmeric itself. Turmeric, a golden spice obtained from the rhizome of the plant Curcuma longa, has been used to give color and taste to food preparations since ancient times. Traditionally, this spice has been used in Ayurveda and folk medicine for the treatment of such ailments as gynecological problems, gastric problems, hepatic disorders, infectious diseases, and blood disorders. Modern science has provided the scientific basis for the use of turmeric against such disorders. Various chemical constituents have been isolated from this spice, including polyphenols, sesquiterpenes, diterpenes, triterpenoids, sterols, and alkaloids. Curcumin, which constitutes 2-5% of turmeric, is perhaps the most-studied component. Although some of the activities of turmeric can be mimicked by curcumin, other activities are curcumin-independent. Cell-based studies have demonstrated the potential of turmeric as an antimicrobial, insecticidal, larvicidal, antimutagenic, radioprotector, and anticancer agent. Numerous animal studies have shown the potential of this spice against proinflammatory diseases, cancer, neurodegenerative diseases, depression, diabetes, obesity, and atherosclerosis. At the molecular level, this spice has been shown to modulate numerous cell-signaling pathways. In clinical trials, turmeric has shown efficacy against numerous human ailments including lupus nephritis, cancer, diabetes, irritable bowel syndrome, acne, and fibrosis. Thus, a spice originally common in the kitchen is now exhibiting activities in the clinic. In this review, we discuss the chemical constituents of turmeric, its biological activities, its molecular targets, and its potential in the clinic. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.","title":"Multitargeting by turmeric, the golden spice: From kitchen to clinic."},{"docid":"MED-4544","text":"Emblica officinalis Gaertn. or Phyllanthus emblica Linn, commonly known as Indian gooseberry or amla, is arguably the most important medicinal plant in the Indian traditional system of medicine, the Ayurveda. Various parts of the plant are used to treat a range of diseases, but the most important is the fruit. The fruit is used either alone or in combination with other plants to treat many ailments such as common cold and fever; as a diuretic, laxative, liver tonic, refrigerant, stomachic, restorative, alterative, antipyretic, anti-inflammatory, hair tonic; to prevent peptic ulcer and dyspepsia, and as a digestive. Preclinical studies have shown that amla possesses antipyretic, analgesic, antitussive, antiatherogenic, adaptogenic, cardioprotective, gastroprotective, antianemia, antihypercholesterolemia, wound healing, antidiarrheal, antiatherosclerotic, hepatoprotective, nephroprotective, and neuroprotective properties. In addition, experimental studies have shown that amla and some of its phytochemicals such as gallic acid, ellagic acid, pyrogallol, some norsesquiterpenoids, corilagin, geraniin, elaeocarpusin, and prodelphinidins B1 and B2 also possess antineoplastic effects. Amla is also reported to possess radiomodulatory, chemomodulatory, chemopreventive effects, free radical scavenging, antioxidant, anti-inflammatory, antimutagenic and immunomodulatory activities, properties that are efficacious in the treatment and prevention of cancer. This review for the first time summarizes the results related to these properties and also emphasizes the aspects that warrant future research to establish its activity and utility as a cancer preventive and therapeutic drug in humans.","title":"Amla (Emblica officinalis Gaertn), a wonder berry in the treatment and prevention of cancer."},{"docid":"MED-2801","text":"Turmeric has been long recognized for its anti-inflammatory and health-promoting properties. Curcumin is one of the principal anti-inflammatory and healthful components of turmeric comprising 2-8% of most turmeric preparations. Experimental evidence supports the activity of curcumin in promoting weight loss and reducing the incidence of obesity-related diseases. With the discovery that obesity is characterized by chronic low-grade metabolic inflammation, phytochemicals like curcumin which have anti-inflammatory activity are being intensely investigated. Recent scientific research reveals that curcumin directly interacts with white adipose tissue to suppress chronic inflammation. In adipose tissue, curcumin inhibits macrophage infiltration and nuclear factor κB (NF-κB) activation induced by inflammatory agents. Curcumin reduces the expression of the potent proinflammatory adipokines tumor necrosis factor-α (TNFα), monocyte chemoattractant protein-1 (MCP-1), and plasminogen activator inhibitor type-1 (PAI-1), and it induces the expression of adiponectin, the principal anti-inflammatory agent secreted by adipocytes. Curcumin also has effects to inhibit adipocyte differentiation and to promote antioxidant activities. Through these diverse mechanisms curcumin reduces obesity and curtails the adverse health effects of obesity. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.","title":"Curcumin and obesity."},{"docid":"MED-2573","text":"A significant anticancer activity of the naturally occurring carbohydrate inositol hexaphosphate (IP(6)) has been reported against numerous cancer models. Since tumors require angiogenesis for growth and metastasis, we hypothesize that IP(6) reduces tumor growth by inhibiting angiogenesis. Because angiogenesis depends on the interaction between endothelial and tumor cells, we investigated the effect of IP(6) on both. IP(6) inhibited the proliferation and induced the differentiation of endothelial cells in vitro; the growth of bovine aortic endothelial cells (BAECs) evaluated by MTT proliferation assay was inhibited in a dose-dependent manner (IC(50) = 0.74 mM). The combination of IP(6) and vasostatin, a calreticulin fragment with anti-angiogenic activity, was synergistically superior in growth inhibition than either compound. IP(6) inhibited human umbilical vein endothelial cell (HUVEC) tube formation (in vitro capillary differentiation) on a reconstituted extracellular matrix, Matrigel, and disrupted pre-formed tubes. IP(6) significantly reduced basic fibroblast growth factor (bFGF)-induced vessel formation (P < 0.01) in vivo in Matrigel plug assay. Exposure of HepG2, a human hepatoma cell line, to IP(6) for 8 h, resulted in a dose-dependent decrease in the mRNA levels of vascular endothelial growth factor (VEGF), as assessed by RT-PCR. IP(6) treatment of HepG2 cells for 24 h also significantly reduced the VEGF protein levels in conditioned medium, in a concentration-dependent manner (P = 0.012). Thus, IP(6) has an inhibitory effect on induced angiogenesis.","title":"Anti-angiogenic activity of inositol hexaphosphate (IP6)."},{"docid":"MED-2988","text":"This review describes the present state of knowledge about phytic acid (phytate), which is often present in legume seeds. The antinutritional effects of phytic acid primarily relate to the strong chelating associated with its six reactive phosphate groups. Its ability to complex with proteins and particularly with minerals has been a subject of investigation from chemical and nutritional viewpoints. The hydrolysis of phytate into inositol and phosphates or phosphoric acid occurs as a result of phytase or nonenzymatic cleavage. Enzymes capable of hydrolysing phytates are widely distributed in micro-organisms, plants and animals. Phytases act in a stepwise manner to catalyse the hydrolysis of phytic acid. To reduce or eliminate the chelating ability of phytate, dephosphorylation of hexa- and penta-phosphate forms is essential since a high degree of phosphorylation is necessary to bind minerals. There are several methods of decreasing the inhibitory effect of phytic acid on mineral absorption (cooking, germination, fermentation, soaking, autolysis). Nevertheless, inositol hexaphosphate is receiving increased attention owing to its role in cancer prevention and/or therapy and its hypocholesterolaemic effect.","title":"The role of phytic acid in legumes: antinutrient or beneficial function?"},{"docid":"MED-2827","text":"Alternative and complementary therapeutic approaches, such as the use of a wide array of herbal, nutritional, and physical manipulations, are becoming popular for relieving symptoms of osteoarthritis (OA). The present study evaluated the efficacy of soy protein (SP) supplementation in relieving the pain and discomfort associated with OA. One hundred and thirty-five free-living individuals (64 men and 71 women) with diagnosed OA or with self-reported chronic knee joint pain not attributed to injury or rheumatoid arthritis were recruited for this double-blind, placebo-controlled, parallel design study. Study participants were assigned randomly to consume 40 g of either supplemental SP or milk-based protein (MP) daily for 3 months. Pain, knee range of motion, and overall physical activity were evaluated prior to the start of treatment and monthly thereafter. Serum levels of glycoprotein 39 (YKL-40), a marker of cartilage degradation, and insulin-like growth factor-I (IGF-I), a growth factor associated with cartilage synthesis, were assessed at baseline and at the end of the study. Overall, SP improved OA-associated symptoms such as range of motion and several factors associated with pain and quality of life in comparison to MP. However, these beneficial effects were mainly due to the effect of SP in men rather than women. Biochemical markers of cartilage metabolism further support the efficacy of SP in men as indicated by a significant increase in serum level of IGF-I and a significant decrease in serum level of YKL-40 compared to MP. This study is the first to provide evidence of possible beneficial effects of SP in the management of OA. Examining and verifying the long-term effects of SP on improving symptoms of OA, particularly in men, is warranted.","title":"Soy protein may alleviate osteoarthritis symptoms."}],"string":"[\n {\n \"docid\": \"MED-2781\",\n \"text\": \"Our previous study demonstrated that curcumin, an active compound of Curcuma xanthorrhiza and C. domestica, produces a positive cholekinetic effect. A 20 mg amount of curcumin is capable of contracting the gall bladder by up to 29% within an observation time of 2 h. The aim of the current study was to define the dosage of curcumin capable of producing a 50% contraction of the gall bladder, and to determine if there is a linear relationship between doubling the curcumin dosage and the doubling of gall bladder contraction. A randomised, single-blind, three-phase, crossover-designed examination was carried out on 12 healthy volunteers. Ultrasonography was carried out serially to measure the gall bladder volume. The data obtained was analysed by analysis of variance (ANOVA). The fasting volumes of gall bladders were similar (P > 0.50), with 17.28 +/- 5.47 mL for 20 mg curcumin, 18.34 +/- 3.75 mL for 40 mg and 18.24 +/- 3.72 mL for 80 mg. The percentage decrease in gall bladder volume 2 h after administration of 20, 40 and 80 mg was 34.10 +/- 10.16, 51.15 +/- 8.08 and 72.25 +/- 8.22, respectively, which was significantly different (P < 0.01). On the basis of the present findings, it appears that the dosage of cucumin capable of producing a 50% contraction of the bladder was 40 mg. This study did not show any linear relationship between doubling curcumin dosage and the doubling of gall bladder contraction.\",\n \"title\": \"Effect of different curcumin dosages on human gall bladder.\"\n },\n {\n \"docid\": \"MED-2819\",\n \"text\": \"OBJECTIVES: Curcumin (diferuloylmethane) is the principal biochemical component of the spice turmeric and has been shown to possess potent anti-catabolic, anti-inflammatory and antioxidant, properties. This article aims to provide a summary of the actions of curcumin on articular chondrocytes from the available literature with the use of a text-mining tool. We highlight both the potential benefits and drawbacks of using this chemopreventive agent for treating osteoarthritis (OA). We also explore the recent literature on the molecular mechanisms of curcumin mediated alterations in gene expression mediated via activator protein 1 (AP-1)/nuclear factor-kappa B (NF-kappaB) signalling in chondrocytes, osteoblasts and synovial fibroblasts. METHODS: A computer-aided search of the PubMed/Medline database aided by a text-mining tool to interrogate the ResNet Mammalian database 6.0. RESULTS: Recent work has shown that curcumin protects human chondrocytes from the catabolic actions of interleukin-1 beta (IL-1beta) including matrix metalloproteinase (MMP)-3 up-regulation, inhibition of collagen type II and down-regulation of beta1-integrin expression. Curcumin blocks IL-1beta-induced proteoglycan degradation, AP-1/NF-kappaB signalling, chondrocyte apoptosis and activation of caspase-3. CONCLUSIONS: The available data from published in vitro and in vivo studies suggest that curcumin may be a beneficial complementary treatment for OA in humans and companion animals. Nevertheless, before initiating extensive clinical trials, more basic research is required to improve its solubility, absorption and bioavailability and gain additional information about its safety and efficacy in different species. Once these obstacles have been overcome, curcumin and structurally related biochemicals may become safer and more suitable nutraceutical alternatives to the non-steroidal anti-inflammatory drugs that are currently used for the treatment of OA. Copyright 2009 Osteoarthritis Research Society International. All rights reserved.\",\n \"title\": \"Biological actions of curcumin on articular chondrocytes.\"\n },\n {\n \"docid\": \"MED-2825\",\n \"text\": \"Turmeric, a dried powder derived from the rhizome of Curcuma longa, has been used for centuries in certain parts of the world and has been linked to numerous biological activities including antioxidant, anti-inflammatory, anticancer, antigrowth, anti-arthritic, anti-atherosclerotic, antidepressant, anti-aging, antidiabetic, antimicrobial, wound healing, and memory-enhancing activities. One component of turmeric is curcumin, which has been extensively studied, as indicated by more than 5600 citations, most of which have appeared within the past decade. Recent research has identified numerous chemical entities from turmeric other than curcumin. It is unclear whether all of the activities ascribed to turmeric are due to curcumin or whether other compounds in turmeric can manifest these activities uniquely, additively, or synergistically with curcumin. However, studies have indicated that turmeric oil, present in turmeric, can enhance the bioavailability of curcumin. Studies over the past decade have indicated that curcumin-free turmeric (CFT) components possess numerous biological activities including anti-inflammatory, anticancer, and antidiabetic activities. Elemene derived from turmeric is approved in China for the treatment of cancer. The current review focuses on the anticancer and anti-inflammatory activities exhibited by CFT and by some individual components of turmeric, including turmerin, turmerone, elemene, furanodiene, curdione, bisacurone, cyclocurcumin, calebin A, and germacrone. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.\",\n \"title\": \"Curcumin-free turmeric exhibits anti-inflammatory and anticancer activities: Identification of novel components of turmeric.\"\n },\n {\n \"docid\": \"MED-4239\",\n \"text\": \"BACKGROUND: Prostate cancer is the most common solid-tumor cancer in US males but is rare in Asian males. When Asian men adopt the US lifestyle, clinical prostate cancer increases greatly. Epidemiological data from men in the US indicate that regular activity may reduce the risk for prostate cancer. METHODS: Serum was obtained from three groups of similar-aged men, Control, Diet and Exercise, and Exercise alone were used to stimulate LNCaP cells in culture. Growth and apoptosis of tumor cells were measured. Serum samples were also used to measure insulin, IGF-1, IGFBP-1. RESULTS: The Diet and Exercise and the Exercise alone groups had lower serum insulin and IGF-1 but higher IGFBP-1 compared to Controls. LNCaP cell growth was reduced in both groups compared to Control and there was a major increase in apoptosis of tumor cells. CONCLUSIONS: A low-fat diet and/or intensive exercise results in change in serum hormones and growth factors in vivo that can reduce growth and induce apoptosis of LNCaP prostate tumor cells in vitro. Copyright 2003 Wiley-Liss, Inc.\",\n \"title\": \"A low-fat diet and/or strenuous exercise alters the IGF axis in vivo and reduces prostate tumor cell growth in vitro.\"\n },\n {\n \"docid\": \"MED-2812\",\n \"text\": \"Curcumin derived from the tropical plant Curcuma longa has a long history of use as a dietary agent, food preservative, and in traditional Asian medicine. It has been used for centuries to treat biliary disorders, anorexia, cough, diabetic wounds, hepatic disorders, rheumatism, and sinusitis. The preventive and therapeutic properties of curcumin are associated with its antioxidant, anti-inflammatory, and anticancer properties. Extensive research over several decades has attempted to identify the molecular mechanisms of curcumin action. Curcumin modulates numerous molecular targets by altering their gene expression, signaling pathways, or through direct interaction. Curcumin regulates the expression of inflammatory cytokines (e.g., TNF, IL-1), growth factors (e.g., VEGF, EGF, FGF), growth factor receptors (e.g., EGFR, HER-2, AR), enzymes (e.g., COX-2, LOX, MMP9, MAPK, mTOR, Akt), adhesion molecules (e.g., ELAM-1, ICAM-1, VCAM-1), apoptosis related proteins (e.g., Bcl-2, caspases, DR, Fas), and cell cycle proteins (e.g., cyclin D1). Curcumin modulates the activity of several transcription factors (e.g., NF-κB, AP-1, STAT) and their signaling pathways. Based on its ability to affect multiple targets, curcumin has the potential for the prevention and treatment of various diseases including cancers, arthritis, allergies, atherosclerosis, aging, neurodegenerative disease, hepatic disorders, obesity, diabetes, psoriasis, and autoimmune diseases. This review summarizes the molecular mechanisms of modulation of gene expression by curcumin. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.\",\n \"title\": \"Molecular mechanisms of curcumin action: gene expression.\"\n },\n {\n \"docid\": \"MED-2604\",\n \"text\": \"Cancer is a hyperproliferative disorder that is usually treated by chemotherapeutic agents that are toxic not only to tumor cells but also to normal cells, so these agents produce major side effects. In addition, these agents are highly expensive and thus not affordable for most. Moreover, such agents cannot be used for cancer prevention. Traditional medicines are generally free of the deleterious side effects and usually inexpensive. Curcumin, a component of turmeric (Curcuma longa), is one such agent that is safe, affordable, and efficacious. How curcumin kills tumor cells is the focus of this review. We show that curcumin modulates growth of tumor cells through regulation of multiple cell signaling pathways including cell proliferation pathway (cyclin D1, c-myc), cell survival pathway (Bcl-2, Bcl-xL, cFLIP, XIAP, c-IAP1), caspase activation pathway (caspase-8, 3, 9), tumor suppressor pathway (p53, p21) death receptor pathway (DR4, DR5), mitochondrial pathways, and protein kinase pathway (JNK, Akt, and AMPK). How curcumin selectively kills tumor cells, and not normal cells, is also described in detail.\",\n \"title\": \"Curcumin and Cancer Cells: How Many Ways Can Curry Kill Tumor Cells Selectively?\"\n },\n {\n \"docid\": \"MED-2605\",\n \"text\": \"Curcumin (diferuloylmethane), the yellow pigment in turmeric (Curcuma longa), is known to inhibit proliferation of cancer cells by arresting them at various phases of the cell cycle and to induce apoptosis in tumor cells. Curcumin-induced apoptosis mainly involves the activation of caspase-3 and mitochondria-mediated pathway in various cancer cells of different tissue origin. In the present study, the induction of apoptosis and cytotoxicity by curcumin in colon cancer colo 205 cells was investigated by using flow cytometry. The results demonstrated that curcumin induced cytotoxicity and apoptosis dose- and time-depedently. Curcumin induced the production of reactive oxygen species (ROS) and Ca+2, decreased the levels of mitochondria membrane potential and induced caspase-3 activity. Curcumin also promoted the expression of Bax, cytochrome C, p53 and p21 but inhibited the expression of Bcl-2. These observations suggest that curcumin may have a possible therapeutic potential in colon cancer patients.\",\n \"title\": \"Curcumin-induced apoptosis of human colon cancer colo 205 cells through the production of ROS, Ca2+ and the activation of caspase-3.\"\n },\n {\n \"docid\": \"MED-2826\",\n \"text\": \"Background Curcumin extracts of turmeric are proposed to produce health benefits. To date, human intervention studies have focused mainly on people with existing health problems given high doses of poorly absorbed curcumin. The purpose of the current study was to check whether in healthy people, a low dose of a lipidated curcumin extract could alter wellness-related measures. Methods The present study was conducted in healthy middle aged people (40–60 years old) with a low dose of curcumin (80 mg/day) in a lipidated form expected to have good absorption. Subjects were given either curcumin (N = 19) or placebo (N = 19) for 4 wk. Blood and saliva samples were taken before and after the 4 weeks and analyzed for a variety of blood and saliva measures relevant to health promotion. Results Curcumin, but not placebo, produced the following statistically significant changes: lowering of plasma triglyceride values, lowering of salivary amylase levels, raising of salivary radical scavenging capacities, raising of plasma catalase activities, lowering of plasma beta amyloid protein concentrations, lowering of plasma sICAM readings, increased plasma myeloperoxidase without increased c-reactive protein levels, increased plasma nitric oxide, and decreased plasma alanine amino transferase activities. Conclusion Collectively, these results demonstrate that a low dose of a curcumin-lipid preparation can produce a variety of potentially health promoting effects in healthy middle aged people.\",\n \"title\": \"Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people\"\n },\n {\n \"docid\": \"MED-2794\",\n \"text\": \"Turmeric, a plant rhizome that is often dried, ground and used as a cooking spice, has also been used medicinally for several thousand years. Curcumin, the phytochemical that gives turmeric its golden color, is responsible for most of the therapeutic effects of turmeric. In recent years curcumin has been studied for its effects on chronic diseases such as diabetes, Alzheimer's, and cancer. Though many researchers are investigating turmeric/curcumin in cancer therapy, there is little epidemiologic information on the effects of turmeric consumption. With limited availability of pharmacologic interventions in many areas of the world, use of turmeric in the diet may help to alleviate some of the disease burden through prevention. Here we provide a brief overview of turmeric consumption in different parts of the world, cancer rates in those regions, possible biochemical mechanisms by which turmeric acts and practical recommendations based on the information available.\",\n \"title\": \"Dietary turmeric potentially reduces the risk of cancer.\"\n },\n {\n \"docid\": \"MED-2814\",\n \"text\": \"Curcumin (diferuloylmethane), an active constituent of turmeric, is a well-described phytochemical, which has been used since ancient times for the treatment of various diseases. The dysregulation of cell signaling pathways by the gradual alteration of regulatory proteins is the root cause of cancers. Curcumin modulates regulatory proteins through various molecular mechanisms. Several research studies have provided in-depth analysis of multiple targets through which curcumin induces protective effects against cancers including gastrointestinal, genitourinary, gynecological, hematological, pulmonary, thymic, brain, breast, and bone. The molecular mechanisms of action of curcumin in treating different types of cancers remain under investigation. The multifaceted role of this dietary agent is mediated through its inhibition of several cell signaling pathways at multiple levels. Curcumin has the ability to inhibit carcinogenicity through the modulation of the cell cycle by binding directly and indirectly to molecular targets including transcription factors (NF-kB, STAT3, β-catenin, and AP-1), growth factors (EGF, PDGF, and VEGF), enzymes (COX-2, iNOS, and MMPs), kinases (cyclin D1, CDKs, Akt, PKC, and AMPK), inflammatory cytokines (TNF, MCP, IL-1, and IL-6), upregulation of proapoptotic (Bax, Bad, and Bak) and downregulation of antiapoptotic proteins (Bcl(2) and Bcl-xL). A variety of animal models and human studies have proven that curcumin is safe and well tolerated even at very high doses. This study elaborates the current understanding of the chemopreventive effects of curcumin through its multiple molecular pathways and highlights its therapeutic value in the treatment and prevention of a wide range of cancers. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.\",\n \"title\": \"Curcumin in various cancers.\"\n },\n {\n \"docid\": \"MED-2810\",\n \"text\": \"Although turmeric (Curcuma longa; an Indian spice) has been described in Ayurveda, as a treatment for inflammatory diseases and is referred by different names in different cultures, the active principle called curcumin or diferuloylmethane, a yellow pigment present in turmeric (curry powder) has been shown to exhibit numerous activities. Extensive research over the last half century has revealed several important functions of curcumin. It binds to a variety of proteins and inhibits the activity of various kinases. By modulating the activation of various transcription factors, curcumin regulates the expression of inflammatory enzymes, cytokines, adhesion molecules, and cell survival proteins. Curcumin also downregulates cyclin D1, cyclin E and MDM2; and upregulates p21, p27, and p53. Various preclinical cell culture and animal studies suggest that curcumin has potential as an antiproliferative, anti-invasive, and antiangiogenic agent; as a mediator of chemoresistance and radioresistance; as a chemopreventive agent; and as a therapeutic agent in wound healing, diabetes, Alzheimer disease, Parkinson disease, cardiovascular disease, pulmonary disease, and arthritis. Pilot phase I clinical trials have shown curcumin to be safe even when consumed at a daily dose of 12g for 3 months. Other clinical trials suggest a potential therapeutic role for curcumin in diseases such as familial adenomatous polyposis, inflammatory bowel disease, ulcerative colitis, colon cancer, pancreatic cancer, hypercholesteremia, atherosclerosis, pancreatitis, psoriasis, chronic anterior uveitis and arthritis. Thus, curcumin, a spice once relegated to the kitchen shelf, has moved into the clinic and may prove to be \\\"Curecumin\\\".\",\n \"title\": \"Curcumin as \\\"Curecumin\\\": from kitchen to clinic.\"\n },\n {\n \"docid\": \"MED-2599\",\n \"text\": \"Curcumin exhibits anti-inflammatory and antitumor activities. Although its functional mechanism has not been elucidated so far, numerous studies have shown that curcumin induces apoptosis in cancer cells. In the present study, we show that subtoxic concentrations of curcumin sensitize human renal cancer cells to the tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-mediated apoptosis. This apoptosis induced by the combination of curcumin and TRAIL is not interrupted by Bcl-2 overexpression. We found that treatment with curcumin significantly induces death receptor 5 (DR5) expression both at its mRNA and protein levels, accompanying the generation of the reactive oxygen species (ROS). Not only the pretreatment with N-acetylcystine but also the ectopic expression of peroxiredoxin II, an antioxidative protein, dramatically inhibited the apoptosis induced by curcumin and TRAIL in combination, blocking the curcumin-mediated DR5 upregulation. Taken together, the present study demonstrates that curcumin enhances TRAIL-induced apoptosis by ROS-mediated DR5 upregulation.\",\n \"title\": \"Curcumin sensitizes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through reactive oxygen species-mediated upre...\"\n },\n {\n \"docid\": \"MED-5337\",\n \"text\": \"PURPOSE: Men with prostate cancer are often advised to make changes in diet and lifestyle, although the impact of these changes has not been well documented. Therefore, we evaluated the effects of comprehensive lifestyle changes on prostate specific antigen (PSA), treatment trends and serum stimulated LNCaP cell growth in men with early, biopsy proven prostate cancer after 1 year. MATERIALS AND METHODS: Patient recruitment was limited to men who had chosen not to undergo any conventional treatment, which provided an unusual opportunity to have a nonintervention randomized control group to avoid the confounding effects of interventions such as radiation, surgery or androgen deprivation therapy. A total of 93 volunteers with serum PSA 4 to 10 ng/ml and cancer Gleason scores less than 7 were randomly assigned to an experimental group that was asked to make comprehensive lifestyle changes or to a usual care control group. RESULTS: None of the experimental group patients but 6 control patients underwent conventional treatment due to an increase in PSA and/or progression of disease on magnetic resonance imaging. PSA decreased 4% in the experimental group but increased 6% in the control group (p = 0.016). The growth of LNCaP prostate cancer cells (American Type Culture Collection, Manassas, Virginia) was inhibited almost 8 times more by serum from the experimental than from the control group (70% vs 9%, p <0.001). Changes in serum PSA and also in LNCaP cell growth were significantly associated with the degree of change in diet and lifestyle. CONCLUSIONS: Intensive lifestyle changes may affect the progression of early, low grade prostate cancer in men. Further studies and longer term followup are warranted.\",\n \"title\": \"Intensive lifestyle changes may affect the progression of prostate cancer.\"\n },\n {\n \"docid\": \"MED-2805\",\n \"text\": \"Obesity is a significant risk factor for developing osteoarthritis in weight-bearing and non-weight-bearing joints. Although the pathogenesis of obesity-associated osteoarthritis is not completely understood, recent studies indicate that pro-inflammatory metabolic factors contribute to an increase in osteoarthritis risk. Adipose tissue, and in particular infrapatellar fat, is a local source of pro-inflammatory mediators that are increased with obesity and have been shown to increase cartilage degradation in cell and tissue culture models. One adipokine in particular, leptin, may be a critical mediator of obesity-associated osteoarthritis via synergistic actions with other inflammatory cytokines. Biomechanical factors may also increase the risk of osteoarthritis by activating cellular inflammation and promoting oxidative stress. However, some types of biomechanical stimulation, such as physiologic cyclic loading, inhibit inflammation and protect against cartilage degradation. A high percentage of obese individuals with knee osteoarthritis are sedentary, suggesting that a lack of physical activity may increase the susceptibility to inflammation. A more comprehensive approach to understanding how obesity alters daily biomechanical exposures within joint tissues may provide new insight into the protective and damaging effects of biomechanical factors on inflammation in osteoarthritis.\",\n \"title\": \"Pathobiology of obesity and osteoarthritis: integrating biomechanics and inflammation\"\n },\n {\n \"docid\": \"MED-2815\",\n \"text\": \"Curcumin, an active polyphenol of the golden spice turmeric, is a highly pleiotropic molecule with the potential to modulate the biological activity of a number of signaling molecules. Traditionally, this polyphenol has been used in Asian countries to treat such human ailments as acne, psoriasis, dermatitis, and rash. Recent studies have indicated that curcumin can target newly identified signaling pathways including those associated with microRNA, cancer stem cells, and autophagy. Extensive research from preclinical and clinical studies has delineated the molecular basis for the pharmaceutical uses of this polyphenol against cancer, pulmonary diseases, neurological diseases, liver diseases, metabolic diseases, autoimmune diseases, cardiovascular diseases, and numerous other chronic diseases. Multiple studies have indicated the safety and efficacy of curcumin in numerous animals including rodents, monkeys, horses, rabbits, and cats and have provided a solid basis for evaluating its safety and efficacy in humans. To date, more than 65 human clinical trials of curcumin, which included more than 1000 patients, have been completed, and as many as 35 clinical trials are underway. Curcumin is now used as a supplement in several countries including the United States, India, Japan, Korea, Thailand, China, Turkey, South Africa, Nepal, and Pakistan. In this review, we provide evidence for the pharmaceutical uses of curcumin for various diseases. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.\",\n \"title\": \"Curcumin, a component of turmeric: from farm to pharmacy.\"\n },\n {\n \"docid\": \"MED-2802\",\n \"text\": \"OBJECTIVE: The objective of this study was to determine the efficacy and safety of Curcuma domestica extracts in pain reduction and functional improvement in patients with knee osteoarthritis. STUDY DESIGN AND SETTING: The design and setting were a randomized controlled study at a university hospital in Bangkok, Thailand. METHODS: One-hundred and seven (107) patients with primary knee osteoarthritis (OA) with pain score of > or =5 were randomized to receive ibuprofen 800 mg per day or C. domestica extracts 2 g per day for 6 weeks. The main outcomes were improvement in pain on level walking, pain on stairs, and functions of knee assessed by time spent during 100-m walk and going up and down a flight of stairs. The adverse events were also recorded. RESULTS: Fifty-two (52) and 55 patients were randomized to C. domestica extracts and ibuprofen groups, respectively. Baseline characteristics of the patients in both groups were not different. The mean scores of the aforementioned outcomes at weeks 0, 2, 4, and 6 were significantly improved when compared with the baseline values in both groups. There was no difference in those parameters between the patients receiving ibuprofen and C. domestica extracts, except pain on stairs (p = 0.016). No significant difference of adverse events between both groups was found (33.3% versus 44.2%, p = 0.36 in C. domestica extracts and ibuprofen groups, respectively). CONCLUSIONS: C. domestica extracts seem to be similarly efficacious and safe as ibuprofen for the treatment of knee OA.\",\n \"title\": \"Efficacy and safety of Curcuma domestica extracts in patients with knee osteoarthritis.\"\n },\n {\n \"docid\": \"MED-2813\",\n \"text\": \"The use of turmeric, derived from the root of the plant Curcuma longa, for treatment of different inflammatory diseases has been described in Ayurveda and in traditional Chinese medicine for thousands of years. The active component of turmeric responsible for this activity, curcumin, was identified almost two centuries ago. Modern science has revealed that curcumin mediates its effects by modulation of several important molecular targets, including transcription factors (e.g., NF-kappaB, AP-1, Egr-1, beta-catenin, and PPAR-gamma), enzymes (e.g., COX2, 5-LOX, iNOS, and hemeoxygenase-1), cell cycle proteins (e.g., cyclin D1 and p21), cytokines (e.g., TNF, IL-1, IL-6, and chemokines), receptors (e.g., EGFR and HER2), and cell surface adhesion molecules. Because it can modulate the expression of these targets, curcumin is now being used to treat cancer, arthritis, diabetes, Crohn's disease, cardiovascular diseases, osteoporosis, Alzheimer's disease, psoriasis, and other pathologies. Interestingly, 6-gingerol, a natural analog of curcumin derived from the root of ginger (Zingiber officinalis), exhibits a biologic activity profile similar to that of curcumin. The efficacy, pharmacologic safety, and cost effectiveness of curcuminoids prompt us to \\\"get back to our roots.\\\"\",\n \"title\": \"Curcumin: getting back to the roots.\"\n },\n {\n \"docid\": \"MED-2583\",\n \"text\": \"Inositol hexaphosphate (IP(6)), a naturally polyphosphorylated carbohydrate, has been reported to have significant in vivo and in vitro anticancer activity against numerous tumours, such as colon, prostate, breast, liver and rhabdomyosarcomas. To confirm this activity in haematological malignancies and to characterize some of the mechanisms of IP(6) action, we analysed its effects on human leukaemic cell lines and fresh chronic myelogenous leukaemia (CML) progenitor cells using a combined cellular and molecular approach. IP(6) had a dose-dependent cytotoxic effect on all of the evaluated cell lines, with accumulation in the G2M phase in two out of five cell lines tested. At the molecular level, cDNA microarray analysis after IP(6) exposure showed an extensive downmodulation of genes involved in transcription and cell cycle regulation and a coherent upregulation of cell cycle inhibitors. Furthermore, IP(6) treatment of fresh leukaemic samples of bone marrow CD34+ CML progenitor cells significantly inhibited granulocyte-macrophage colony-forming unit (CFU-GM) formation (P = 0.0062) in comparison to normal bone marrow specimens, which were not affected. No differentiating effect on HL60 cells was observed. Taken together, our results confirm the antiproliferative activity of IP(6) and suggest that it may have a specific antitumour effect also in chronic myeloid leukaemias, via active gene modulation.\",\n \"title\": \"Effect of inositol hexaphosphate (IP(6)) on human normal and leukaemic haematopoietic cells.\"\n },\n {\n \"docid\": \"MED-2786\",\n \"text\": \"Alzheimer's disease (AD) is the most common form of dementia. There is limited choice in modern therapeutics, and drugs available have limited success with multiple side effects in addition to high cost. Hence, newer and alternate treatment options are being explored for effective and safer therapeutic targets to address AD. Turmeric possesses multiple medicinal uses including treatment for AD. Curcuminoids, a mixture of curcumin, demethoxycurcumin, and bisdemethoxycurcumin, are vital constituents of turmeric. It is generally believed that curcumin is the most important constituent of the curcuminoid mixture that contributes to the pharmacological profile of parent curcuminoid mixture or turmeric. A careful literature study reveals that the other two constituents of the curcuminoid mixture also contribute significantly to the effectiveness of curcuminoids in AD. Therefore, it is emphasized in this review that each component of the curcuminoid mixture plays a distinct role in making curcuminoid mixture useful in AD, and hence, the curcuminoid mixture represents turmeric in its medicinal value better than curcumin alone. The progress in understanding the disease etiology demands a multiple-site-targeted therapy, and the curcuminoid mixture of all components, each with different merits, makes this mixture more promising in combating the challenging disease. Copyright © 2013 John Wiley & Sons, Ltd.\",\n \"title\": \"Therapeutic potential of turmeric in Alzheimer's disease: curcumin or curcuminoids?\"\n },\n {\n \"docid\": \"MED-2809\",\n \"text\": \"Extensive research over the past half century has shown that curcumin (diferuloylmethane), a component of the golden spice turmeric (Curcuma longa), can modulate multiple cell signaling pathways. Extensive clinical trials over the past quarter century have addressed the pharmacokinetics, safety, and efficacy of this nutraceutical against numerous diseases in humans. Some promising effects have been observed in patients with various pro-inflammatory diseases including cancer, cardiovascular disease, arthritis, uveitis, ulcerative proctitis, Crohn’s disease, ulcerative colitis, irritable bowel disease, tropical pancreatitis, peptic ulcer, gastric ulcer, idiopathic orbital inflammatory pseudotumor, oral lichen planus, gastric inflammation, vitiligo, psoriasis, acute coronary syndrome, atherosclerosis, diabetes, diabetic nephropathy, diabetic microangiopathy, lupus nephritis, renal conditions, acquired immunodeficiency syndrome, β-thalassemia, biliary dyskinesia, Dejerine-Sottas disease, cholecystitis, and chronic bacterial prostatitis. Curcumin has also shown protection against hepatic conditions, chronic arsenic exposure, and alcohol intoxication. Dose-escalating studies have indicated the safety of curcumin at doses as high as 12 g/day over 3 months. Curcumin’s pleiotropic activities emanate from its ability to modulate numerous signaling molecules such as pro-inflammatory cytokines, apoptotic proteins, NF–κB, cyclooxygenase-2, 5-LOX, STAT3, C-reactive protein, prostaglandin E2, prostate-specific antigen, adhesion molecules, phosphorylase kinase, transforming growth factor-β, triglyceride, ET-1, creatinine, HO-1, AST, and ALT in human participants. In clinical trials, curcumin has been used either alone or in combination with other agents. Various formulations of curcumin, including nanoparticles, liposomal encapsulation, emulsions, capsules, tablets, and powder, have been examined. In this review, we discuss in detail the various human diseases in which the effect of curcumin has been investigated.\",\n \"title\": \"Therapeutic Roles of Curcumin: Lessons Learned from Clinical Trials\"\n },\n {\n \"docid\": \"MED-4220\",\n \"text\": \"OBJECTIVE: Accumulating evidence indicates that prostate cancer is associated with high levels of serum IGF-I. This study was conducted to determine whether a low-fat diet and exercise (DE) intervention may modulate the IGF axis and reduce prostate cancer cell growth in vitro. METHODS: Fasting serum was obtained from 14 men (age 60 +/- 3 years) participating in an 11-day DE program and from eight similarly aged men who had followed the DE program for 14.2 +/- 1.7 years (long-term). Insulin, IGF-I, IGFBP-1, and IGFBP-3 were measured by ELISA, and serum was used to stimulate LNCaP cell growth in vitro. RESULTS: Serum IGF-I levels decreased by 20% while IGFBP-1 increased by 53% after 11-day DE. In the long-term group, IGF-I was 55% lower, while IGFBP-1 was 150% higher relative to baseline. Serum insulin decreased by 25% after 11-day DE and was 68% lower in the long-term group, relative to baseline. No changes in serum IGFBP-3 were observed. Serum-stimulated LNCaP cell growth was reduced by 30% in post-11-day serum and by 44% in long-term serum relative to baseline. LNCaP cells incubated with post-DE serum showed increased apoptosis/ necrosis, compared to baseline. CONCLUSIONS: A low-fat diet and exercise intervention induces in-vivo changes in the circulating IGF axis and is associated with reduced growth and enhanced apoptosis/necrosis of LNCaP tumor cells in vitro.\",\n \"title\": \"Effect of diet and exercise on serum insulin, IGF-I, and IGFBP-1 levels and growth of LNCaP cells in vitro (United States).\"\n },\n {\n \"docid\": \"MED-2822\",\n \"text\": \"Curcumin is known to possess potent antiinflammatory and antiarthritic properties. This pilot clinical study evaluated the safety and effectiveness of curcumin alone, and in combination with diclofenac sodium in patients with active rheumatoid arthritis (RA). Forty-five patients diagnosed with RA were randomized into three groups with patients receiving curcumin (500 mg) and diclofenac sodium (50 mg) alone or their combination. The primary endpoints were reduction in Disease Activity Score (DAS) 28. The secondary endpoints included American College of Rheumatology (ACR) criteria for reduction in tenderness and swelling of joint scores. Patients in all three treatment groups showed statistically significant changes in their DAS scores. Interestingly, the curcumin group showed the highest percentage of improvement in overall DAS and ACR scores (ACR 20, 50 and 70) and these scores were significantly better than the patients in the diclofenac sodium group. More importantly, curcumin treatment was found to be safe and did not relate with any adverse events. Our study provides the first evidence for the safety and superiority of curcumin treatment in patients with active RA, and highlights the need for future large-scale trials to validate these findings in patients with RA and other arthritic conditions. Copyright © 2012 John Wiley & Sons, Ltd.\",\n \"title\": \"A randomized, pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis.\"\n },\n {\n \"docid\": \"MED-2793\",\n \"text\": \"Piperine, a major active component of black and long peppers, has been reported to enhance drug bioavailability. The present studies were aimed at understanding the interaction of piperine with enzymatic drug biotransforming reactions in hepatic tissue in vitro and in vivo. Piperine inhibited arylhydrocarbon hydroxylation, ethylmorphine-N-demethylation, 7-ethoxycoumarin-O-deethylation and 3-hydroxy-benzo(a)pyrene glucuronidation in rat postmitochondrial supernatant in vitro in a dose-dependent manner. Piperine inhibition of these reactions in postmitochondrial supernatant from 3-methylcholanthrene- and phenobarbital-treated rats was similar to the controls. Inhibition by piperine of arylhydrocarbon hydroxylase (AHH) from 3-methylcholanthrene-treated rats was comparable to that observed with 7,8-benzoflavone. Piperine caused noncompetitive inhibition of hepatic microsomal AHH from the untreated and 3-methylcholanthrene-treated rats with a Ki of 30 microM which was close to the apparent Km of AHH observed in the controls. Similarly, the kinetics of inhibition of ethylmorphine-N-demethylase from control rat liver microsomes exhibited noncompetitive inhibition with an apparent Km of 0.8 mM and Ki of 35 microM. These studies demonstrated that piperine is a nonspecific inhibitor of drug metabolism which shows little discrimination between different cytochrome P-450 forms. Oral administration of piperine in rats strongly inhibited the hepatic AHH and UDP-glucuronyltransferase activities. The maximal inhibition of AHH observed within 1 hr restored to normal value in 6 hr. Pretreatment with piperine prolonged hexobarbital sleeping time and zoxazolamine paralysis time in mice at half the dose of SKF-525A. These results demonstrate that piperine is a potent inhibitor of drug metabolism.\",\n \"title\": \"Biochemical basis of enhanced drug bioavailability by piperine: evidence that piperine is a potent inhibitor of drug metabolism.\"\n },\n {\n \"docid\": \"MED-2601\",\n \"text\": \"It has been reported that curcumin inhibited various types of cancer cells in vitro and in vivo. However, mechanisms of curcumin-inhibited cell growth and -induced apoptosis in human non-small cell lung cancer cells (NCI-H460) still remain unclear. In this study, NCI-H460 cells were treated with curcumin to determine its anticancer activity. Different concentrations of curcumin were used for different durations in NCI-H460 cells and the subsequent changes in the cell morphology, viability, cell cycle, mRNA and protein expressions were determined. Curcumin induced apoptotic morphologic changes in NCI-H460 cells in a dose-dependent manner. After curcumin treatment, BAX and BAD were up-regulated, BCL-2, BCL-X(L) and XIAP were down-regulated. In addition, reactive oxygen species (ROS), intracellular Ca(2+) and endoplasmic reticulum (ER) stress were increased in NCI-H460 cells after exposure to curcumin. These signals led to a loss of mitochondrial membrane potential (Delta Psi(m)) and culminated in caspase-3 activation. Curcumin-induced apoptosis was also stimulated through the FAS/caspase-8 (extrinsic) pathway and ER stress proteins, growth arrest- and DNA damage-inducible gene 153 (GADD153) and glucose-regulated protein 78 (GRP78) were activated in the NCI-H460 cells. Apoptotic cell death induced by curcumin was significantly reversed by pretreatment with ROS scavenger or caspase-8 inhibitor. Furthermore, the NCI-H460 cells tended to be arrested at the G(2)/M cell cycle stage after curcumin treatment and down-regulation of cyclin-dependent kinase 1 (CDK1) may be involved. In summary, curcumin exerts its anticancer effects on lung cancer NCI-H460 cells through apoptosis or cell cycle arrest.\",\n \"title\": \"Curcumin induces apoptosis in human non-small cell lung cancer NCI-H460 cells through ER stress and caspase cascade- and mitochondria-dependent pat...\"\n },\n {\n \"docid\": \"MED-4543\",\n \"text\": \"Phyllanthus emblica Linn. (PE) is a medicinal fruit used in many Asian traditional medicine systems for the treatment of various diseases including cancer. The present study tested the potential anticancer effects of aqueous extract of PE in four ways: (1) against cancer cell lines, (2) in vitro apoptosis, (3) mouse skin tumourigenesis and (4) in vitro invasiveness. The PE extract at 50-100 microg/mL significantly inhibited cell growth of six human cancer cell lines, A549 (lung), HepG2 (liver), HeLa (cervical), MDA-MB-231 (breast), SK-OV3 (ovarian) and SW620 (colorectal). However, the extract was not toxic against MRC5 (normal lung fibroblast). Apoptosis in HeLa cells was also observed as PE extract caused DNA fragmentation and increased activity of caspase-3/7 and caspase-8, but not caspase-9, and up-regulation of the Fas protein indicating a death receptor-mediated mechanism of apoptosis. Treatment of PE extract on mouse skin resulted in over 50% reduction of tumour numbers and volumes in animals treated with DMBA/TPA. Lastly, 25 and 50 microg/mL of PE extract inhibited invasiveness of MDA-MB-231 cells in the in vitro Matrigel invasion assay. These results suggest P. emblica exhibits anticancer activity against selected cancer cells, and warrants further study as a possible chemopreventive and antiinvasive agent. Copyright 2010 John Wiley & Sons, Ltd.\",\n \"title\": \"Antitumour effects of Phyllanthus emblica L.: induction of cancer cell apoptosis and inhibition of in vivo tumour promotion and in vitro invasion o...\"\n },\n {\n \"docid\": \"MED-2585\",\n \"text\": \"Inositol hexaphosphate (IP6) is a naturally occurring polyphosphorylated carbohydrate that is present in substantial amounts in almost all plant and mammalian cells. It was recently recognized to possess multiple biological functions. A striking anticancer effect of IP6 was demonstrated in different experimental models. Inositol is also a natural constituent possessing moderate anticancer activity. The most consistent and best anticancer results were obtained from the combination of IP6 plus inositol. In addition to reducing cell proliferation, IP6 increases differentiation of malignant cells, often resulting in a reversion to normal phenotype. Exogenously administered IP6 is rapidly taken into the cells and dephosphorylated to lower-phosphate inositol phosphates, which further interfere with signal transduction pathways and cell cycle arrest. Enhanced immunity and antioxidant properties can also contribute to tumor cell destruction. However, the molecular mechanisms underlying this anticancer action are not fully understood. Because it is abundantly present in regular diet, efficiently absorbed from the gastrointestinal tract, and safe, IP6 holds great promise in our strategies for the prevention and treatment of cancer. IP6 plus inositol enhances the anticancer effect of conventional chemotherapy, controls cancer metastases, and improves the quality of life, as shown in a pilot clinical trial. The data strongly argue for the use of IP6 plus inositol in our strategies for cancer prevention and treatment. However, the effectiveness and safety of IP6 plus inositol at therapeutic doses needs to be determined in phase I and phase II clinical trials in humans.\",\n \"title\": \"Cancer inhibition by inositol hexaphosphate (IP6) and inositol: from laboratory to clinic.\"\n },\n {\n \"docid\": \"MED-2572\",\n \"text\": \"In traditional cultures, balancing health with a balanced lifestyle was a core belief. The diseases of modern civilization were rare. Indigenous people have patterns of illness very different from Western civilization; yet, they rapidly develop diseases once exposed to Western foods and lifestyles. Food and medicine were interwoven. All cultures used special or functional foods to prevent disease. Food could be used at different times either as food or medicine. Foods, cultivation, and cooking methods maximized community health and well-being. With methods passed down through generations, cooking processes were utilized that enhanced mineral and nutrient bioavailability. This article focuses on what researchers observed about the food traditions of indigenous people, their disease patterns, the use of specific foods, and the environmental factors that affect people who still eat traditional foods.\",\n \"title\": \"Traditional non-Western diets.\"\n },\n {\n \"docid\": \"MED-2820\",\n \"text\": \"Scope The incidence of cancer is significantly lower in regions where turmeric is heavily consumed. Whether lower cancer incidence is due to turmeric was investigated by examining its effects on tumor cell proliferation, on pro-inflammatory transcription factors NF-κB and STAT3, and on associated gene products. Methods and results Cell proliferation and cell cytotoxicity were measured by the MTT method, NF-κB activity by EMSA, protein expression by Western blot analysis, ROS generation by FACS analysis, and osteoclastogenesis by TRAP assay. Turmeric inhibited NF-κB activation and down-regulated NF-κB-regulated gene products linked to survival (Bcl-2, cFLIP, XIAP, and cIAP1), proliferation (cyclin D1 and c-Myc), and metastasis (CXCR4) of cancer cells. The spice suppressed the activation of STAT3, and induced the death receptors (DR)4 and DR5. Turmeric enhanced the production of ROS, and suppressed the growth of tumor cell lines. Furthermore, turmeric sensitized the tumor cells to chemotherapeutic agents capecitabine and taxol. Turmeric was found to be more potent than pure curcumin for cell growth inhibition. Turmeric also inhibited NF-κB activation induced by RANKL that correlated with the suppression of osteoclastogenesis. Conclusion Our results indicate that turmeric can effectively block the proliferation of tumor cells through the suppression of NF-κB and STAT3 pathways.\",\n \"title\": \"Turmeric (Curcuma longa) inhibits inflammatory nuclear factor (NF)-κB and NF-κB-regulated gene products and induces death receptors leading to suppressed proliferation, induced chemosensitization, and suppressed osteoclastogenesis\"\n },\n {\n \"docid\": \"MED-2787\",\n \"text\": \"BACKGROUND: The extract of medicinal plants containing curcumin is traditionally believed to have a positive contraction effect on the human gall-bladder. AIMS: To compare the effect of 20 mg curcumin or placebo on the gall-bladder volume of healthy volunteers. METHODS: A randomized, double blind and crossover design study was carried out in 12 healthy volunteers (seven males and five females). Ultrasonography examination was carried out serially to measure the gall-bladder volume. The data obtained was analysed by paired Student's t-test. RESULTS: The fasting gall-bladder volumes of 15.74 +/- 4.29 mL on curcumin and 15.98 +/- 4.08 mL on placebo were similar (P > 0.20). The gall-bladder volume was reduced within the period after curcumin administration. The percentage of gall-bladder volume reduction at 0.5, 1.0, 1.5 and 2.0 h after 20 mg curcumin administration were 11.8 +/- 6.9, 16.8 +/- 7.4, 22.0 +/- 8.5 and 29. 3 +/- 8.3%, respectively, which was statistically significant compared to placebo. CONCLUSION: On the basis of the present findings, it appears that curcumin induces contraction of the human gall-bladder.\",\n \"title\": \"The effect of curcumin and placebo on human gall-bladder function: an ultrasound study.\"\n },\n {\n \"docid\": \"MED-2790\",\n \"text\": \"Vasa (Adhatoda vasica Linn.) is a well known and easily available drug in almost all the seasons. Easy availability of any drug gains popularity among physicians as well as pharmaceuticals and this is the reason why almost every Kalpana of Vasa is found described in the Ayurvedika text. The different dosage forms of Vasa like Kvatha, Avaleha, Sneha, and Sandhana have been used for the treatment of Shwasa Roga. A number of research studies have been performed on different formulations of Vasa and its effect on Shwasa Roga. Therefore, a review study has been carried out on the Vasa extract, Vasa Avaleha (prepared from Svarasa and Kvatha), Vasa Ghrita, Vasarishta, and Vasakasava on Shwasa Roga, to know which formulation is better. It was found in the review that Vasa Ghana, Vasa Ghrita (1), and Vasa Avaleha have shown good results on Tamaka Shwasa.\",\n \"title\": \"A clinical review of different formulations of Vasa (Adhatoda vasica) on Tamaka Shwasa (asthma)\"\n },\n {\n \"docid\": \"MED-2777\",\n \"text\": \"BACKGROUND: Gout, an inflammatory arthritis, reportedly afflicts more than 2 million men and women in the United States. Previous reports have suggested an association between gout and kidney stone disease; however, these studies did not adjust for such important potential confounders as obesity and the presence of hypertension. To our knowledge, no published study has examined the independent association between gout and kidney stone disease. METHODS: We used a national probability sample of the US population to determine the independent association between reported gout and history of kidney stone disease. RESULTS: Among men and women 20 years and older, 5.6% (10 million) reported the previous passage of a kidney stone and 2.7% (5.1 million) reported a diagnosis of gout by a physician. Moreover, 8.6% of individuals who reported the passage of a kidney stone on two or more occasions had a history of gout. Conversely, the prevalence of previous kidney stones in subjects with reported gout was 13.9%. In the age-adjusted model, gout was associated with an increased odds ratio (OR) for previous kidney stones (OR, 1.97; 95% confidence interval [CI], 1.37 to 2.83). After further adjustment for sex, race, body mass index, and presence of hypertension, the OR for previous kidney stones in individuals with gout decreased to 1.49 (95% CI, 1.04 to 2.14). CONCLUSION: Showing an independent association between kidney stone disease and gout strongly suggests that they share common underlying pathophysiological mechanisms. Identification of these mechanisms may lead to improved preventive strategies for both conditions. Copyright 2002 by the National Kidney Foundation, Inc.\",\n \"title\": \"The association between gout and nephrolithiasis: the National Health and Nutrition Examination Survey III, 1988-1994.\"\n },\n {\n \"docid\": \"MED-4612\",\n \"text\": \"Amino acids modulate the secretion of both insulin and glucagon; the composition of dietary protein therefore has the potential to influence the balance of glucagon and insulin activity. Soy protein, as well as many other vegan proteins, are higher in non-essential amino acids than most animal-derived food proteins, and as a result should preferentially favor glucagon production. Acting on hepatocytes, glucagon promotes (and insulin inhibits) cAMP-dependent mechanisms that down-regulate lipogenic enzymes and cholesterol synthesis, while up-regulating hepatic LDL receptors and production of the IGF-I antagonist IGFBP-1. The insulin-sensitizing properties of many vegan diets--high in fiber, low in saturated fat--should amplify these effects by down-regulating insulin secretion. Additionally, the relatively low essential amino acid content of some vegan diets may decrease hepatic IGF-I synthesis. Thus, diets featuring vegan proteins can be expected to lower elevated serum lipid levels, promote weight loss, and decrease circulating IGF-I activity. The latter effect should impede cancer induction (as is seen in animal studies with soy protein), lessen neutrophil-mediated inflammatory damage, and slow growth and maturation in children. In fact, vegans tend to have low serum lipids, lean physiques, shorter stature, later puberty, and decreased risk for certain prominent 'Western' cancers; a vegan diet has documented clinical efficacy in rheumatoid arthritis. Low-fat vegan diets may be especially protective in regard to cancers linked to insulin resistance--namely, breast and colon cancer--as well as prostate cancer; conversely, the high IGF-I activity associated with heavy ingestion of animal products may be largely responsible for the epidemic of 'Western' cancers in wealthy societies. Increased phytochemical intake is also likely to contribute to the reduction of cancer risk in vegans. Regression of coronary stenoses has been documented during low-fat vegan diets coupled with exercise training; such regimens also tend to markedly improve diabetic control and lower elevated blood pressure. Risk of many other degenerative disorders may be decreased in vegans, although reduced growth factor activity may be responsible for an increased risk of hemorrhagic stroke. By altering the glucagon/insulin balance, it is conceivable that supplemental intakes of key non-essential amino acids could enable omnivores to enjoy some of the health advantages of a vegan diet. An unnecessarily high intake of essential amino acids--either in the absolute sense or relative to total dietary protein--may prove to be as grave a risk factor for 'Western' degenerative diseases as is excessive fat intake.\",\n \"title\": \"Vegan proteins may reduce risk of cancer, obesity, and cardiovascular disease by promoting increased glucagon activity.\"\n },\n {\n \"docid\": \"MED-2831\",\n \"text\": \"TNFs are major mediators of inflammation and inflammation-related diseases, hence, the United States Food and Drug Administration (FDA) has approved the use of blockers of the cytokine, TNF-α, for the treatment of osteoarthritis, inflammatory bowel disease, psoriasis and ankylosis. These drugs include the chimeric TNF antibody (infliximab), humanized TNF-α antibody (Humira) and soluble TNF receptor-II (Enbrel) and are associated with a total cumulative market value of more than $20 billion a year. As well as being expensive ($15 000–20 000 per person per year), these drugs have to be injected and have enough adverse effects to be given a black label warning by the FDA. In the current report, we describe an alternative, curcumin (diferuloylmethane), a component of turmeric (Curcuma longa) that is very inexpensive, orally bioavailable and highly safe in humans, yet can block TNF-α action and production in in vitro models, in animal models and in humans. In addition, we provide evidence for curcumin's activities against all of the diseases for which TNF blockers are currently being used. Mechanisms by which curcumin inhibits the production and the cell signalling pathways activated by this cytokine are also discussed. With health-care costs and safety being major issues today, this golden spice may help provide the solution. Linked Articles This article is part of a themed section on Emerging Therapeutic Aspects in Oncology. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.169.issue-8\",\n \"title\": \"Curcumin: an orally bioavailable blocker of TNF and other pro-inflammatory biomarkers\"\n },\n {\n \"docid\": \"MED-2574\",\n \"text\": \"Inositol hexaphosphate (IP(6)) is a naturally occurring polyphosphorylated carbohydrate, abundantly present in many plant sources and in certain high-fiber diets, such as cereals and legumes. In addition to being found in plants, IP(6) is contained in almost all mammalian cells, although in much smaller amounts, where it is important in regulating vital cellular functions such as signal transduction, cell proliferation, and differentiation. For a long time IP(6) has been recognized as a natural antioxidant. Recently IP(6) has received much attention for its role in cancer prevention and control of experimental tumor growth, progression, and metastasis. In addition, IP(6) possesses other significant benefits for human health, such as the ability to enhance immune system, prevent pathological calcification and kidney stone formation, lower elevated serum cholesterol, and reduce pathological platelet activity. In this review we show the efficacy and discuss some of the molecular mechanisms that govern the action of this dietary agent. Exogenously administered IP(6) is rapidly taken up into cells and dephosphorylated to lower inositol phosphates, which further affect signal transduction pathways resulting in cell cycle arrest. A striking anticancer action of IP(6) was demonstrated in different experimental models. In addition to reducing cell proliferation, IP(6) also induces differentiation of malignant cells. Enhanced immunity and antioxidant properties also contribute to tumor cell destruction. Preliminary studies in humans show that IP(6) and inositol, the precursor molecule of IP(6), appear to enhance the anticancer effect of conventional chemotherapy, control cancer metastases, and improve quality of life. Because it is abundantly present in regular diet, efficiently absorbed from the gastrointestinal tract, and safe, IP(6) + inositol holds great promise in our strategies for cancer prevention and therapy. There is clearly enough evidence to justify the initiation of full-scale clinical trials in humans.\",\n \"title\": \"Protection against cancer by dietary IP6 and inositol.\"\n },\n {\n \"docid\": \"MED-4114\",\n \"text\": \"Induced apoptosis of autoreactive T-lymphocyte precursors in the thymus is crucial for the prevention of autoimmune disorders. IGF-I and prolactin, which are lymphocyte growth factors, may have the potential to suppress apoptosis in thymocytes and thus encourage autoimmunity; conversely, dietary fish oil rich in omega-3 fats appears to upregulate apoptosis in lymphocytes. Since whole-food vegan diets may downregulate systemic IGF-I activity, it is proposed that such a diet, in conjunction with fish oil supplementation and treatment with dopamine agonists capable of suppressing prolactin secretion, may have utility for treating and preventing autoimmune disorders. This prediction is consistent with the extreme rarity of autoimmune disorders among sub-Saharan black Africans as long as they followed their traditional quasi-vegan lifestyles, and with recent ecologic studies correlating risks for IDDM and for multiple sclerosis mortality with animal product and/or saturated fat consumption. Moreover, there is evidence that vegan or quasi-vegan diets are useful in the management of rheumatoid arthritis, multiple sclerosis, and possibly SLE. The dopamine agonist bromocryptine exerts anti-inflammatory effects in rodent models of autoimmunity, and there is preliminary evidence that this drug may be clinically useful in several human autoimmune diseases; better tolerated D2-specific agonists such as cabergoline may prove to be more practical for use in therapy. The moderate clinical utility of supplemental fish oil in rheumatoid arthritis and certain other autoimmune disorders is documented. It is not unlikely that extra-thymic anti-inflammatory effects contribute importantly to the clinical utility of vegan diets, bromocryptine, and fish oil in autoimmunity. The favorable impact of low latitude or high altitude on autoimmune risk may be mediated by superior vitamin D status, which is associated with decreased secretion of parathyroid hormone; there are theoretical grounds for suspecting that parathyroid hormone may inhibit apoptosis in thymocytes. Androgens appear to up-regulate thymocyte apoptosis, may be largely responsible for the relative protection from autoimmunity enjoyed by men, and merit further evaluation for the management of autoimmunity in women. It will probably prove more practical to prevent autoimmune disorders than to reverse them once established; a whole-food vegan diet, coupled with fish oil and vitamin D supplementation, may represent a practical strategy for achieving this prevention, while concurrently lowering risk for many other life-threatening 'Western' diseases. Copyright 2001 Harcourt Publishers Ltd.\",\n \"title\": \"Upregulation of lymphocyte apoptosis as a strategy for preventing and treating autoimmune disorders: a role for whole-food vegan diets, fish oil an...\"\n },\n {\n \"docid\": \"MED-2816\",\n \"text\": \"Plants contain numerous polyphenols, which have been shown to reduce inflammation and hereby to increase resistance to disease. Examples of such polyphenols are isothiocyanates in cabbage and broccoli, epigallocatechin in green tee, capsaicin in chili peppers, chalones, rutin and naringenin in apples, resveratrol in red wine and fresh peanuts and curcumin/curcuminoids in turmeric. Most diseases are maintained by a sustained discreet but obvious increased systemic inflammation. Many studies suggest that the effect of treatment can be improved by a combination of restriction in intake of proinflammatory molecules such as advanced glycation end products (AGE), advanced lipoperoxidation end products (ALE), and rich supply of antiinflammatory molecules such as plant polyphenols. To the polyphenols with a bulk of experimental documentation belong the curcuminoid family and especially its main ingredient, curcumin. This review summarizes the present knowledge about these turmericderived ingredients, which have proven to be strong antioxidants and inhibitors of cyclooxigenase-2 (COX-2), lipoxygenase (LOX) and nuclear factor kappa B (NF-kappaB) but also AGE. A plethora of clinical effects are reported in various experimental diseases, but clinical studies in humans are few. It is suggested that supply of polyphenols and particularly curcuminoids might be value as complement to pharmaceutical treatment, but also prebiotic treatment, in conditions proven to be rather therapy-resistant such as Crohn's, long-stayed patients in intensive care units, but also in conditions such as cancer, liver cirrhosis, chronic renal disease, chronic obstructive lung disease, diabetes and Alzheimer's disease.\",\n \"title\": \"Plant-derived health: the effects of turmeric and curcuminoids.\"\n },\n {\n \"docid\": \"MED-2780\",\n \"text\": \"Spices, such as cinnamon, cloves, cardamom, garlic, ginger, cumin, coriander and turmeric are used all over the world as flavouring and colouring ingredients in Indian foods. Previous studies have shown that spices contain variable amounts of total oxalates but there are few reports of soluble oxalate contents. In this study, the total, soluble and insoluble oxalate contents of ten different spices commonly used in Indian cuisine were measured. Total oxalate content ranged from 194 (nutmeg) to 4,014 (green cardamom) mg/100 g DM, while the soluble oxalate contents ranged from 41 (nutmeg) to 3,977 (green cardamom) mg/100 g DM. Overall, the percentage of soluble oxalate content of the spices ranged from 4.7 to 99.1% of the total oxalate content which suggests that some spices present no risk to people liable to kidney stone formation, while other spices can supply significant amounts of soluble oxalates and therefore should be used in moderation.\",\n \"title\": \"Total and soluble oxalate content of some Indian spices.\"\n },\n {\n \"docid\": \"MED-2800\",\n \"text\": \"The management of osteoarthritis represents a real challenge. This complex and multi-factorial disease evolves over decades and requires not only the alleviation of symptoms, i.e. pain and joint function but also the preservation of articular structure without side effects. Nutraceuticals are good candidates for the management of OA due to their safety profile and potential efficacy. However, they are not part of the treatment guidelines and published recommendations. Curcumin is the yellow pigment isolated from the rhizomes of Curcuma longa, commonly known as turmeric. Curcumin is a highly pleiotropic molecule with an excellent safety profile. Strong molecular evidence has been published for its potency to target multiple inflammatory diseases. However, naturally occurring curcumin cannot achieve its optimum therapeutic outcomes due to its low solubility and poor bioavailability. Nevertheless, curcumin presents great potential for treating OA and has been categorized as having preclinical evidence of efficacy. This review aimed at gathering most of the available information to document the potential efficacy of curcumin based on the results obtained in in vitro models of cartilage and osteoarthritis and in other diseases.\",\n \"title\": \"Curcumin: a new paradigm and therapeutic opportunity for the treatment of osteoarthritis: curcumin for osteoarthritis management\"\n },\n {\n \"docid\": \"MED-2582\",\n \"text\": \"Nonstarch polysaccharide (NSP) intake was measured in representative samples of 30 men aged 50-59 in 2 urban and 2 rural Scandinavian populations that exhibited a 3-4 fold difference in incidence of large bowel cancer. Intake was measured by chemical analysis of complete duplicate portions of all food eaten over one day by each individual. NSP intakes showed a rural-urban gradient, with 18.4 +/- 7.8 g/day in rural Finland and 18.0 +/- 6.4 g/day in rural Denmark versus 14.5 +/- 5.4 g/day in urban Finland and 13.2 +/- 4.8 g/day in urban Denmark. NSP intakes were also calculated (using food tables) from weighed food records kept over 4 days, one of which was the day on which the duplicate collection was made. Intakes were 2-2.5 g/day higher with this method than with direct chemical analysis, mainly because published tables of values have become outdated and inaccurate as a result of improved methods for measuring NSP in food. Individual variation from day to day in NSP intake was considerable. Average NSP intake and intake of some of its component sugars were inversely related to colon cancer incidence in this geographical comparison. To show a relationship at the individual level between diet and cancer risk in a prospective study would require detailed and accurate methods for the assessment of NSP consumption.\",\n \"title\": \"Nonstarch polysaccharide consumption in four Scandinavian populations.\"\n },\n {\n \"docid\": \"MED-2782\",\n \"text\": \"BACKGROUND & AIMS: Curcumin is a biologically active phytochemical substance present in turmeric and has pharmacologic actions that might benefit patients with ulcerative colitis (UC). The aim in this trial was to assess the efficacy of curcumin as maintenance therapy in patients with quiescent ulcerative colitis (UC). METHODS: Eighty-nine patients with quiescent UC were recruited for this randomized, double-blind, multicenter trial of curcumin in the prevention of relapse. Forty-five patients received curcumin, 1g after breakfast and 1g after the evening meal, plus sulfasalazine (SZ) or mesalamine, and 44 patients received placebo plus SZ or mesalamine for 6 months. Clinical activity index (CAI) and endoscopic index (EI) were determined at entry, every 2 months (CAI), at the conclusion of 6-month trial, and at the end of 6-month follow-up. RESULTS: Seven patients were protocol violators. Of 43 patients who received curcumin, 2 relapsed during 6 months of therapy (4.65%), whereas 8 of 39 patients (20.51%) in the placebo group relapsed (P=.040). Recurrence rates evaluated on the basis of intention to treat showed significant difference between curcumin and placebo (P=.049). Furthermore, curcumin improved both CAI (P=.038) and EI (P=.0001), thus suppressing the morbidity associated with UC. A 6-month follow-up was done during which patients in both groups were on SZ or mesalamine. Eight additional patients in the curcumin group and 6 patients in the placebo group relapsed. CONCLUSIONS: Curcumin seems to be a promising and safe medication for maintaining remission in patients with quiescent UC. Further studies on curcumin should strengthen our findings.\",\n \"title\": \"Curcumin maintenance therapy for ulcerative colitis: randomized, multicenter, double-blind, placebo-controlled trial.\"\n },\n {\n \"docid\": \"MED-2785\",\n \"text\": \"Curcumin is extensively used as a spice and pigment and has anticarcinogenic effects that could be linked to its antioxidant properties. However, some studies suggest that this natural compound possesses both pro- and antioxidative effects. In this study, we found that curcumin induced DNA damage to both the mitochondrial and nuclear genomes in human hepatoma G2 cells. Using quantitative polymerase chain reaction and immunocytochemistry staining of 8-hydroxydeoxyguanosine, we demonstrated that curcumin induced dose-dependent damage in both the mitochondrial and nuclear genomes and that the mitochondrial damage was more extensive. Nuclear DNA fragments were also evident in comet assays. The mechanism underlies the elevated level of reactive oxygen species and lipid peroxidation generated by curcumin. The lack of DNA damage at low doses suggested that low levels of curcumin does not induce DNA damage and may play an antioxidant role in carcinogenesis. But at high doses, we found that curcumin imposed oxidative stress and damaged DNA. These data reinforce the hypothesis that curcumin plays a conflicting dual role in carcinogenesis. Also, the extensive mitochondrial DNA damage might be an initial event triggering curcumin-induced cell death.\",\n \"title\": \"Mitochondrial and nuclear DNA damage induced by curcumin in human hepatoma G2 cells.\"\n },\n {\n \"docid\": \"MED-2559\",\n \"text\": \"Inositol hexaphosphate (IP6) has anti-cancer properties, but recently other extracellular functions have been observed for IP6, including enhancing superoxide production and phagocytosis by neutrophils in the presence of microbial stimuli. This study investigated other inflammatory functions of IP6 on adherent neutrophils. The effect of IP6 on the release of IL-8, tumour necrosis factor (TNF-alpha) and IL-6 by neutrophils attached to either plastic or laminin for up to 6 hours in response to stimulation with lipopolysaccharide or N-formyl-Met-Leu-Phe (fMLP) was investigated. An increase in IL-8 secretion by stimulated cells occurred in the presence of IP6. The incubation of cells attached to laminin with IP6 alone (100-250 BM) did not effect cell morphology, but in the presence of 10(-7) M fMLP altered cell shape. A direct effect of IP6 on cell function was to trigger a sustained assembly of F-actin. Thus, exposure of neutrophils to low levels of IP6 appears to modulate selective neutrophil functions.\",\n \"title\": \"Effect of IP6 on human neutrophil cytokine production and cell morphology.\"\n },\n {\n \"docid\": \"MED-2568\",\n \"text\": \"Inositol hexaphosphate (InsP6 or IP6) is ubiquitous. At 10 microM to 1 mM concentrations, IP6 and its lower phosphorylated forms (IP(1-5)) as well as inositol (Ins) are contained in most mammalian cells, wherein they are important in regulating vital cellular functions such as signal transduction, cell proliferation and differentiation. A striking anti-cancer action of IP6 has been demonstrated both in vivo and in vitro, which is based on the hypotheses that exogenously administered IP6 may be internalized, dephosphorylated to IP(1-5), and inhibit cell growth. There is additional evidence that Ins alone may further enhance the anti-cancer effect of IP6. Besides decreasing cellular proliferation, IP6 also causes differentiation of malignant cells often resulting in a reversion to normal phenotype. These data strongly point towards the involvement of signal transduction pathways, cell cycle regulatory genes, differentiation genes, oncogenes and perhaps, tumor suppressor genes in bringing about the observed anti-neoplastic action of IP6.\",\n \"title\": \"IP6: a novel anti-cancer agent.\"\n },\n {\n \"docid\": \"MED-2575\",\n \"text\": \"Introduction Matrix metalloproteinases (MMPs) have repeatedly been shown to play a very active role in extracellular matrix degradation associated with tumor invasion and metastasis. Tissue inhibitors of MMPs (TIMPs) are well-known for their ability to inhibit MMP activity thereby inhibiting malignant progression. Inositol hexaphosphate (IP6 phytic acid) has been recognized to have both preventive and therapeutic effects against various cancers including that of colon. In in vitro studies, IP6 has been demonstrated to inhibit cancer cell adhesion and migration. In the present study, the effect of IP6 on the expression of MMP and TIMP genes was evaluated in unstimulated and IL-1β-stimulated colon cancer cell line Caco-2. Materials and methods Real-time QRT-PCR was used to validate the transcription level of selected MMP and TIMP genes in Caco-2 cells after treatment with 1 ng/ml of IL-1β, 2.5 mM of IP6, and both for 6, 12, and 24 h. Results Stimulation of cells with IL-1β only resulted in an overexpression of MMP and their TIMP mRNAs. A significant decrease in MMP-13, MMP-3, MMP-2, and TIMP-1 basal expression was achieved by IP6. IP6 was also an efficient downregulator of MMP-1, MMP-9, and TIMP-2 genes transcription stimulated by IL-1β in 6 h lasting culture. After 12 h, IL-1β-induced MMP-2 mRNA expression was significantly reduced by IP6. Conclusion Proinflammatory cytokine IL-1β upregulates MMP and TIMP mRNAs expression in colon cancer epithelial cells Caco-2. IP6 (2.5 mM) influences constitutive expression of both MMP and TIMP genes and downregulates IL-1β stimulated transcription of some of these genes. IP6 exerts its anti-metastatic activity through modulation of MMP and TIMP genes expression to prevent cancer cell migration and invasion.\",\n \"title\": \"The effect of inositol hexaphosphate on the expression of selected metalloproteinases and their tissue inhibitors in IL-1β-stimulated colon cancer cells\"\n },\n {\n \"docid\": \"MED-2791\",\n \"text\": \"Curcumin, a polyphenolic compound derived from dietary spice turmeric, possesses diverse pharmacologic effects including anti-inflammatory, antioxidant, antiproliferative and antiangiogenic activities. Phase I clinical trials have shown that curcumin is safe even at high doses (12 g/day) in humans but exhibit poor bioavailability. Major reasons contributing to the low plasma and tissue levels of curcumin appear to be due to poor absorption, rapid metabolism, and rapid systemic elimination. To improve the bioavailability of curcumin, numerous approaches have been undertaken. These approaches involve, first, the use of adjuvant like piperine that interferes with glucuronidation; second, the use of liposomal curcumin; third, curcumin nanoparticles; fourth, the use of curcumin phospholipid complex; and fifth, the use of structural analogues of curcumin (e.g., EF-24). The latter has been reported to have a rapid absorption with a peak plasma half-life. Despite the lower bioavailability, therapeutic efficacy of curcumin against various human diseases, including cancer, cardiovascular diseases, diabetes, arthritis, neurological diseases and Crohn's disease, has been documented. Enhanced bioavailability of curcumin in the near future is likely to bring this promising natural product to the forefront of therapeutic agents for treatment of human disease.\",\n \"title\": \"Bioavailability of curcumin: problems and promises.\"\n },\n {\n \"docid\": \"MED-2807\",\n \"text\": \"In a previous three-month study of Meriva, a proprietary curcumin-phosphatidylcholine phytosome complex, decreased joint pain and improvement in joint function were observed in 50 osteoarthritis (OA) patients. Since OA is a chronic condition requiring prolonged treatment, the long-term efficacy and safety of Meriva were investigated in a longer (eight months) study involving 100 OA patients. The clinical end points (Western Ontario and McMaster Universities [WOMAC] score, Karnofsky Performance Scale Index, and treadmill walking performance) were complemented by the evaluation of a series of inflammatory markers (interleukin [IL]-1beta, IL-6, soluble CD40 ligand [sCD40L], soluble vascular cell adhesion molecule (sVCAM)-1, and erythrocyte sedimentation rate [ESR]). This represents the most ambitious attempt, to date, to evaluate the clinical efficacy and safety of curcumin as an anti-inflammatory agent. Significant improvements of both the clinical and biochemical end points were observed for Meriva compared to the control group. This, coupled with an excellent tolerability, suggests that Meriva is worth considering for the long-term complementary management of osteoarthritis.\",\n \"title\": \"Efficacy and safety of Meriva®, a curcumin-phosphatidylcholine complex, during extended administration in osteoarthritis patients.\"\n },\n {\n \"docid\": \"MED-2578\",\n \"text\": \"The incidence of colonic cancer differs widely between various human populations. It has been suggested that dietary fiber content is of utmost importance and is inversely related to the occurrence of colonic cancer. However, high-fiber diets are not always correlated with low frequency of colonic cancer, suggesting the involvement of additional dietary constituents. Inositol hexaphosphate (phytic acid) is an abundant plant seed component present in many, but not all, fiber-rich diets. The authors have found that phytic acid is a potent inhibitor of iron-mediated generation of the hazardous oxidant, hydroxyl radical. Herein, the authors propose that inhibition of intracolonic hydroxyl radical generation, via the chelation of reactive iron by phytic acid, may help explain the suppression of colonic carcinogenesis and other inflammatory bowel diseases by diets rich in phytic acid.\",\n \"title\": \"Dietary suppression of colonic cancer. Fiber or phytate?\"\n },\n {\n \"docid\": \"MED-2804\",\n \"text\": \"Osteoarthritis (OA) is the most common form of arthritis in the US, and a leading cause of disability. It is typically defined in epidemiologic studies on the basis of radiographic findings and consideration of symptoms. Its incidence and prevalence are rising, likely related to the aging of the population and increasing obesity. Risk factors for OA include a number of person-level factors, such as age, sex, obesity, and genetics, as well as joint-specific factors that are likely reflective of abnormal loading of the joints. A number of methodologic challenges exist in studying OA that can hamper our ability to identify pertinent relationships.\",\n \"title\": \"Epidemiology of OA\"\n },\n {\n \"docid\": \"MED-2797\",\n \"text\": \"Osteoarthritis (OA) has long been considered a \\\"wear and tear\\\" disease leading to loss of cartilage. OA used to be considered the sole consequence of any process leading to increased pressure on one particular joint or fragility of cartilage matrix. Progress in molecular biology in the 1990s has profoundly modified this paradigm. The discovery that many soluble mediators such as cytokines or prostaglandins can increase the production of matrix metalloproteinases by chondrocytes led to the first steps of an \\\"inflammatory\\\" theory. However, it took a decade before synovitis was accepted as a critical feature of OA, and some studies are now opening the way to consider the condition a driver of the OA process. Recent experimental data have shown that subchondral bone may have a substantial role in the OA process, as a mechanical damper, as well as a source of inflammatory mediators implicated in the OA pain process and in the degradation of the deep layer of cartilage. Thus, initially considered cartilage driven, OA is a much more complex disease with inflammatory mediators released by cartilage, bone and synovium. Low-grade inflammation induced by the metabolic syndrome, innate immunity and inflammaging are some of the more recent arguments in favor of the inflammatory theory of OA and highlighted in this review. Copyright © 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.\",\n \"title\": \"Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!).\"\n },\n {\n \"docid\": \"MED-2788\",\n \"text\": \"Turmeric root has been used medicinally in China and India for thousands of years. The active components are thought to be the curcuminoids, primarily curcumin, which is commonly available worldwide as a standardized extract. This article reviews the pharmacology of curcuminoids, their use and efficacy, potential adverse effects, and dosage and standardization. Preclinical studies point to mechanisms of action that are predominantly anti-inflammatory and antineoplastic, while early human clinical trials suggest beneficial effects for dyspepsia, peptic ulcer, inflammatory bowel disease, rheumatoid arthritis, osteoarthritis, uveitis, orbital pseudotumor, and pancreatic cancer. Curcumin is well-tolerated; the most common side effects are nausea and diarrhea. Theoretical interactions exist due to purported effects on metabolic enzymes and transport proteins, but clinical reports do not support any meaningful interactions. Nonetheless, caution, especially with chemotherapy agents, is advised. Late-phase clinical trials are still needed to confirm most beneficial effects.\",\n \"title\": \"Clinical utility of curcumin extract.\"\n },\n {\n \"docid\": \"MED-2602\",\n \"text\": \"In this study, we investigated the molecular pathways targeted by curcumin during apoptosis of human melanoma cell lines. We found that curcumin caused cell death in eight melanoma cell lines, four with wild-type and four with mutant p53. We demonstrate that curcumin-induced apoptosis is both dose- and time-dependent. We found that curcumin did not induce p53, suggesting that curcumin activates other apoptosis pathways. Our data show that curcumin activates caspases-3 and -8 but not caspase-9, supporting the rationale that apoptosis occurs via a membrane-mediated mechanism. Both a caspase-8 and broad-based caspase inhibitor, but not a caspase-9 specific inhibitor, suppressed curcumin-induced cell death. To further support our hypothesis that curcumin induces activation of a death receptor pathway, we show that curcumin induces Fas receptor aggregation in a FasL-independent manner and that low-temperature incubation, previously shown to inhibit receptor aggregation, prevented curcumin-induced cell death. Moreover, we demonstrate that expression of dominant negative FADD significantly inhibited curcumin-induced cell death. In addition, our results indicate that curcumin also blocks the NF-kappaB cell survival pathway and suppresses the apoptotic inhibitor, XIAP. Since melanoma cells with mutant p53 are strongly resistant to conventional chemotherapy, curcumin may overcome the chemoresistance of these cells and provide potential new avenues for treatment.\",\n \"title\": \"Curcumin induces apoptosis in human melanoma cells through a Fas receptor/caspase-8 pathway independent of p53.\"\n },\n {\n \"docid\": \"MED-5341\",\n \"text\": \"The present study investigated the effects of a diet and exercise intervention on known breast cancer (BCa) risk factors, including estrogen, obesity, insulin, and insulin-like growth factor-I (IGF-I), in overweight/obese, postmenopausal women. In addition, using the subjects' pre- and postintervention serum in vitro, serum-stimulated growth and apoptosis of three estrogen receptor-positive BCa cell lines were studied. The women where placed on a low-fat (10-15% kcal), high-fiber (30-40 g per 1,000 kcal/day) diet and attended daily exercise classes for 2 wk. Serum estradiol was reduced in the women on hormone treatment (HT; n = 28) as well as those not on HT (n = 10). Serum insulin and IGF-I were significantly reduced in all women, whereas IGF binding protein-1 was increased significantly. In vitro growth of the BCa cell lines was reduced by 6.6% for the MCF-7 cells, 9.9% for the ZR-75-1 cells, and 18.5% for the T-47D cells. Apoptosis was increased by 20% in the ZR-75-1 cells, 23% in the MCF-7 cells, and 30% in the T-47D cells (n = 12). These results show that a very-low-fat, high-fiber diet combined with daily exercise results in major reductions in risk factors for BCa while subjects remained overweight/obese. These in vivo serum changes slowed the growth and induced apoptosis in serum-stimulated BCa cell lines in vitro.\",\n \"title\": \"Effects of a low-fat, high-fiber diet and exercise program on breast cancer risk factors in vivo and tumor cell growth and apoptosis in vitro.\"\n },\n {\n \"docid\": \"MED-2579\",\n \"text\": \"There are now extensive scientific data suggesting the potential role of dietary and non-dietary phytochemicals in the prevention and control of prostate cancer (PCA) growth and progression. PCA is a disease of elderly male populations with a relatively slower rate of growth and progression as compared to most other cancers and, therefore, is a candidate disease for preventive intervention. Overall, PCA growth and progression involve aberrant mitogenic and survival signaling and deregulated cell cycle progression, accompanied by gradual accumulation of genetic and epigenetic changes over a period of years. Several mechanisms, including overexpression of growth, survival and angiogenic factors and their receptors, together with a loss/decrease of tumor suppressor p53, retinoblastoma and cyclin-dependent kinase inhibitor, have been implicated in PCA growth and progression. Therefore, phytochemicals targeting these molecular events could have a promising role in PCA prevention and/or therapy. Inositol hexaphosphate (IP6) is a major constituent of most cereals, legumes, nuts, oil seeds and soybean. Taken orally as an over-the-counter dietary/nutrient supplement, and is recognised as offering several health benefits without any known toxicity. In vitro anticancer efficacy of IP6 has been observed in many human, mouse and rat prostate cancer cells. Completed studies also show that oral feeding of IP6 inhibits human PCA xenograft growth in nude mice without toxicity. In a recently completed pilot study, we observed similar preventive effects of IP6 on prostate tumorigenesis in the TRAMP model. Mechanistic studies indicate that IP6 targets mitogenic and survival signaling, as well as cell cycle progression, in PCA cells. IP6 is also shown to target molecular events associated with angiogenesis. Moreover, IP6 has pleiotropic molecular targets for its overall efficacy against PCA and, therefore, could be a suitable candidate agent for preventive intervention of this malignancy in humans.\",\n \"title\": \"Prostate cancer and inositol hexaphosphate: efficacy and mechanisms.\"\n },\n {\n \"docid\": \"MED-2570\",\n \"text\": \"The functional properties, including antioxidant and chemopreventative capacities as well as the inhibitory effects on angiotensin-converting enzyme (ACE), α-glucosidase and pancreatic lipase, of three Australian-grown faba bean genotypes (Nura, Rossa and TF(Ic*As)*483/13) were investigated using an array of in vitro assays. Chromatograms of on-line post column derivatisation assay coupled with HPLC revealed the existence of active phenolics (hump) in the coloured genotypes, which was lacking in the white-coloured breeding line, TF(Ic*As)*483/13. Roasting reduced the phenolic content, and diminished antioxidant activity by 10-40 % as measured by the reagent-based assays (diphenylpicrylhydrazyl, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) and oxygen radical absorbance capacity) in all genotypes. Cell culture-based antioxidant activity assay (cellular antioxidant activity) showed an increase of activity in the coloured genotypes after roasting. Faba bean extracts demonstrated cellular protection ability against H₂O₂-induced DNA damage (assessed using RAW264.7 cells), and inhibited the proliferation of all human cancer cell lines (BL13, AGS, Hep G2 and HT-29) evaluated. However, the effect of faba bean extracts on the non-transformed human cells (CCD-18Co) was negligible. Flow cytometric analyses showed that faba bean extracts successfully induced apoptosis of HL-60 (acute promyelocytic leukaemia) cells. The faba bean extracts also exhibited ACE, α-glucosidase and pancreatic lipase inhibitory activities. Overall, extracts from Nura (buff-coloured) and Rossa (red-coloured) were comparable, while TF(Ic*As)*483/13 (white-coloured) contained the lowest phenolic content and exhibited the least antioxidant and enzyme inhibition activities. These results are important to promote the utilisation of faba beans in human diets for various health benefits.\",\n \"title\": \"In vitro investigations of the potential health benefits of Australian-grown faba beans (Vicia faba L.): chemopreventative capacity and inhibitory ...\"\n },\n {\n \"docid\": \"MED-2817\",\n \"text\": \"Curcumin (diferuloylmethane), a yellow coloring agent extracted from turmeric is also used as a remedy for the treatment and prevention of inflammatory diseases. Acute and chronic inflammation is a major factor in the progression of obesity, type II diabetes, arthritis, pancreatitis, cardiovascular, neurodegenerative and metabolic diseases, as well as certain types of cancer. Turmeric has a long history of use in Ayurvedic medicine for the treatment of inflammatory disorders. Recent studies on the efficacy and therapeutic applicability of turmeric have suggested that the active ingredient of tumeric is curcumin. Further, compelling evidence has shown that curcumin has the ability to inhibit inflammatory cell proliferation, invasion, and angiogenesis through multiple molecular targets and mechanisms of action. Curcumin is safe, non-toxic, and mediates its anti-inflammatory effects through the down-regulation of inflammatory transcription factors, cytokines, redox status, protein kinases, and enzymes that all promote inflammation. In addition, curcumin induces apoptosis through mitochondrial and receptor-mediated pathways, as well as activation of caspase cascades. In the current study, the anti-inflammatory effects of curcumin were evaluated relative to various chronic inflammatory diseases. Based on the available pharmacological data obtained from in vitro and in vivo research, as well as clinical trials, an opportunity exists to translate curcumin into clinics for the prevention of inflammatory diseases in the near future. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.\",\n \"title\": \"Curcumin in inflammatory diseases.\"\n },\n {\n \"docid\": \"MED-4113\",\n \"text\": \"Clonal deletion is arguably the most important mechanism of eliminating self-reactive thymocytes from the T-cell repertoire. Recent work has identified new players in this process. On the thymocyte side, several molecules have been newly implicated in the pathway from initial T-cell receptor signaling through to the final result: gene transcription and thymocyte apoptosis. In addition, several proapoptotic molecules have been found to be necessary for the death of self-reactive thymocytes. On the antigen-presenting cell side, the expression of peripheral self-antigens, regulated at least in part by the autoimmune regulator (AIRE) protein, is crucial for complete elimination of autoreactive thymocytes. The importance of thymic peripheral antigen expression and clonal deletion to self-tolerance is demonstrated in the autoimmune diseases autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy and type-1 diabetes mellitus.\",\n \"title\": \"Good riddance: Thymocyte clonal deletion prevents autoimmunity.\"\n },\n {\n \"docid\": \"MED-2598\",\n \"text\": \"Death receptors belong to the TNF receptor family and are characterised by an intracellular death domain that serves to recruit adapter proteins such as TRADD and FADD and cysteine proteases such as Caspase-8. Activation of Caspase-8 on the aggregated receptor leads to apoptosis. Triggering of death receptors is mediated through the binding of specific ligands of the TNF family, which are homotrimeric type-2 membrane proteins displaying three receptor binding sites. There are various means of modulating the activation of death receptors. The status of the ligand (membrane-bound vs. soluble) is critical in the activation of Fas and of TRAIL receptors. Cleavage of membrane-bound FasL to a soluble form (sFasL) does not affect its ability to bind to Fas but drastically decreases its cytotoxic activity. Conversely, cross-linking epitope-tagged sFasL with anti-tag antibodies to mimic membrane-bound ligand results in a 1000-fold increase in cytotoxicity. This suggests that more than three Fas molecules need to be aggregated to efficiently signal apoptosis. Death receptors can also be regulated by decoy receptors. The cytotoxic ligand TRAIL interacts with five receptors, only two of which (TRAIL-R1 and -R2) have a death domain. TRAIL-R3 is anchored to the membrane by a glycolipid and acts as a dominant negative inhibitor of TRAIL-mediated apoptosis when overexpressed on TRAIL-sensitive cells. Intracellular proteins interacting with the apoptotic pathway are potential modulators of death receptors. FLIP resembles Caspase-8 in structure but lacks protease activity. It interacts with both FADD and Caspase-8 to inhibits the apoptotic signal of death receptors and, at the same time, can activate other signalling pathways such as that leading to NF-kappa B activation.\",\n \"title\": \"Apoptosis induced by death receptors.\"\n },\n {\n \"docid\": \"MED-2803\",\n \"text\": \"Osteoarthritis is a condition caused in part by injury, loss of cartilage structure and function, and an imbalance in inflammatory and anti-inflammatory pathways. It primarily affects the articular cartilage and subchondral bone of synovial joints and results in joint failure, leading to pain upon weight bearing including walking and standing. There is no cure for osteoarthritis, as it is very difficult to restore the cartilage once it is destroyed. The goals of treatment are to relieve pain, maintain or improve joint mobility, increase the strength of the joints and minimize the disabling effects of the disease. Recent studies have shown an association between dietary polyphenols and the prevention of osteoarthritis-related musculoskeletal inflammation. This review discusses the effects of commonly consumed polyphenols, including curcumin, epigallocatechin gallate and green tea extract, resveratrol, nobiletin and citrus fruits, pomegranate, as well as genistein and soy protein, on osteoarthritis with an emphasis on molecular antiosteoarthritic mechanisms. Copyright © 2012 Elsevier Inc. All rights reserved.\",\n \"title\": \"Dietary polyphenols and mechanisms of osteoarthritis.\"\n },\n {\n \"docid\": \"MED-2830\",\n \"text\": \"OBJECTIVE: The aim of this work was to determine the bioavailability of herbs and spices after human consumption by measuring the ability to protect lymphocytes from an oxidative injury and by examining the impact on inflammatory biomarkers in activated THP-1 cells. METHODS: Ten to 12 subjects in each of 13 groups consumed a defined amount of herb or spice for 7 days. Blood was drawn from subjects before consumption and 1 hour after taking the final herb or spice capsules. Subject serum and various extractions of the herbs and spices were analyzed for antioxidant capacity by oxygen radical absorbance capacity (ORAC) analysis or by 1,1-diphenyl-2-picrylhydrzyl (DPPH). Subject peripheral blood mononuclear cells (PBMCs) in medium with10% autologous serum were incubated with hydrogen peroxide to induce DNA strand breaks. Subject serum was also used to treat activated THP-1 cells to determine relative quantities of 3 inflammatory cytokine (tumor necrosis factor-α [TNF-α], interleukin-1α [IL-1α], and IL-6) mRNAs. RESULTS: Herbs and spices that protected PBMCs against DNA strand breaks were paprika, rosemary, ginger, heat-treated turmeric, sage, and cumin. Paprika also appeared to protect cells from normal apoptotic processes. Of the 3 cytokine mRNAs studied (TNF-α, IL-1α, and IL-6), TNF-α was the most sensitive responder to oxidized LDL-treated macrophages. Clove, ginger, rosemary, and turmeric were able to significantly reduce oxidized LDL-induced expression of TNF-α. Serum from those consuming ginger reduced all three inflammatory biomarkers. Ginger, rosemary, and turmeric showed protective capacity by both oxidative protection and inflammation measures. CONCLUSIONS: DNA strand breaks and inflammatory biomarkers are a good functional measure of a food's bioavailability.\",\n \"title\": \"Bioavailability of herbs and spices in humans as determined by ex vivo inflammatory suppression and DNA strand breaks.\"\n },\n {\n \"docid\": \"MED-4319\",\n \"text\": \"The article gives an overview of phytic acid in food and of its significance for human nutrition. It summarises phytate sources in foods and discusses problems of phytic acid/phytate contents of food tables. Data on phytic acid intake are evaluated and daily phytic acid intake depending on food habits is assessed. Degradation of phytate during gastro-intestinal passage is summarised, the mechanism of phytate interacting with minerals and trace elements in the gastro-intestinal chyme described and the pathway of inositol phosphate hydrolysis in the gut presented. The present knowledge of phytate absorption is summarised and discussed. Effects of phytate on mineral and trace element bioavailability are reported and phytate degradation during processing and storage is described. Beneficial activities of dietary phytate such as its effects on calcification and kidney stone formation and on lowering blood glucose and lipids are reported. The antioxidative property of phytic acid and its potentional anticancerogenic activities are briefly surveyed. Development of the analysis of phytic acid and other inositol phosphates is described, problems of inositol phosphate determination and detection discussed and the need for standardisation of phytic acid analysis in foods argued.\",\n \"title\": \"Phytate in foods and significance for humans: food sources, intake, processing, bioavailability, protective role and analysis.\"\n },\n {\n \"docid\": \"MED-2821\",\n \"text\": \"The purpose of this review is to summarize the pertinent literature published in the present era regarding the antiulcerogenic property of curcumin against the pathological changes in response to ulcer effectors (Helicobacter pylori infection, chronic ingestion of non-steroidal anti-inflammatory drugs, and exogenous substances). The gastrointestinal problems caused by different etiologies was observed to be associated with the alterations of various physiologic parameters such as reactive oxygen species, nitric oxide synthase, lipid peroxidation, and secretion of excessive gastric acid. Gastrointestinal ulcer results probably due to imbalance between the aggressive and the defensive factors. In 80% of the cases, gastric ulcer is caused primarily due to the use of non-steroidal anti-inflammatory category of drug, 10% by H. pylori, and about 8-10% by the intake of very spicy and fast food. Although a number of antiulcer drugs and cytoprotectants are available, all these drugs have side effects and limitations. In the recent years a widespread search has been launched to identify new antiulcer drugs from synthetic and natural resources. An Indian dietary derivative (curcumin), a yellow pigment found in the rhizome of Curcuma longa, has been widely used for the treatment of several diseases. Epidemiologically, it was suggested that curcumin might reduce the risk of inflammatory disorders, such as cancer and ulcer. These biological effects are attributed to its anti-inflammatory and antioxidant activities. It can, therefore, be reported from the literature that curcumin PRevents gastrointestinal-induced ulcer and can be recommended as a novel drug for ulcer treatment.\",\n \"title\": \"Turmeric (curcumin) remedies gastroprotective action\"\n },\n {\n \"docid\": \"MED-4112\",\n \"text\": \"Co-stimulatory signals through the CD28 receptor enhance the survival of T cells that have their antigen receptor (TCR) engaged. Here we show that stimulation through the CD28 receptor in the absence of TCR engagement with either an anti-CD28 cross-linking antibody or the CD80 ligand transiently increases expression of the insulin-like growth factor-I receptor (IGF-IR) on T cells. Antibodies that block signaling through the IGF-IR decrease the survival of T cells activated through the TCR and CD28 in the presence of IL-2 by more than 50%, and also enhance susceptibility to Fas-induced apoptosis. CD28 stimulation increases IGF-IR expression on Jurkat cells, and exogenously added IGF-I can protect these cells from Fas-induced apoptosis. We conclude that CD28-mediated enhancement of IGF-IR expression provides activated T cells with essential survival signals that are independent of survival mediated by IL-2 and Bcl-xl.\",\n \"title\": \"The insulin-like growth factor-I receptor is regulated by CD28 and protects activated T cells from apoptosis.\"\n },\n {\n \"docid\": \"MED-2581\",\n \"text\": \"A hospital-based case-control study of diet and colorectal cancer was conducted among Chinese in Singapore (who constitute 77% of the population). A total of 203 cases and 425 controls were included. A history of the usual dietary intake one year prior to interview was taken using a quantitative food frequency questionnaire. Daily intakes of nutrients and selected food items were computed and stratified by tertiles of the control range, to assess risk in low-, medium- and high-intake categories. Effects were adjusted in analysis for age, sex, Chinese dialect group and occupation. For cancers of colon and rectum combined, significant observations were a protective effect of high cruciferous vegetable intake (OR = 0.50, p less than 0.01) and a predisposing effect of a high meat/vegetable consumption ratio (OR = 1.77, p less than 0.05). Similar results were observed for colon cancer alone. For rectal cancer alone (only 71 cases), significant (p less than 0.05) protective effects were observed for high intakes of protein (OR = 0.61), fibre (OR = 0.46), beta-carotene (OR = 0.54), cruciferous vegetables (OR = 0.51) and total vegetables (OR = 0.51). When further assessed by multiple logistic regression, tests for trend and assessment of risk in the extreme highest and lowest quintiles of the control range, the factors consistently significant were cruciferous vegetable intake and the meat/vegetable ratio. A particularly high relative risk was also noted in association with low coffee consumption (OR = 1.59, with p less than 0.05 for trend). No consistent trends were noted for fat or fibre intakes. For non-dietary variables investigated, a history of cholecystectomy increased the risk of both cancers combined (OR = 3.43, p less than 0.05) and colon cancer alone (OR = 4.39, p less than 0.01). This study in an Asian population of countries of Southern and Eastern Asia newly undergoing industrialization and in which rapid economic change is reflected in changing cancer patterns, suggests that the protective effects of certain dietary constituents, notably the cruciferous vegetables, may be more important than the hitherto stressed carcinogenic potential of fat and protein.\",\n \"title\": \"Colorectal cancer and diet in an Asian population--a case-control study among Singapore Chinese.\"\n },\n {\n \"docid\": \"MED-2603\",\n \"text\": \"FAS-associated protein with death domain (FADD) is the key adaptor protein transmitting apoptotic signals mediated by the main death receptors (DRs). Besides being an essential instrument in cell death, FADD is also implicated in proliferation, cell cycle progression, tumor development, inflammation, innate immunity, and autophagy. Recently, many of these new functions of FADD were shown to be independent of DRs. Moreover, FADD function is dictated by protein localization and phosphorylation state. Thus, FADD is a crucial and unique controller of many essential cellular processes. The full understanding of the networks dictating the ultimate function of FADD may provide a new paradigm for other multifaceted proteins. Copyright 2010 Elsevier Ltd. All rights reserved.\",\n \"title\": \"FADD: a regulator of life and death.\"\n },\n {\n \"docid\": \"MED-2808\",\n \"text\": \"Chemotherapy remains the core of anticancer treatment. However, despite the tremendous strides made in the development of targeted anticancer therapies, emergence of resistance to chemotherapeutic drugs is still a major obstacle in the successful management of resistant tumours. Therefore, profound investigation into the in-depth molecular mechanisms of drug resistance is essential and may hopefully translate into effective therapies that can flip the switch from drug resistance to susceptibility. Mechanistically, resistance phenomena may be explained by (i) overexpression of drug efflux pumps, (ii) enhanced drug detoxification, (iii) rapid DNA repair efficiency, (iv) defects in apoptosis regulation, and (v) active cell survival signals. Several adverse effects associated with multidrug resistance and the need for safe multi-targeted anticancer drugs instigated the use of the phytochemical, curcumin, the yellow pigment of the spice turmeric, which has pleotropic activities. We performed a structured literature review using PubMed and Medline searches with secondary review of cited publications, identifying studies on the role of curcumin in conquering drug resistance in cancer. This review describes how curcumin sensitizes cancer cells through regulation of multiple multidrug resistance pathways, thus employing one drug for multiple targets. Curcumin helps the cancer cells to regain their 'forgotten' apoptosis, modulates drug-target interaction at different levels, restrains survival pathways when their proteins are overexpressed, and finds an alternate way to carry forward the process of sensitization of different resistant tumours. Additionally, the review dissects the role of curcumin, if any, in targeting the major culprit of drug resistance, cancer stem cells (CSC), thereby circumventing resistance. Taken together, this review strongly suggests that curcumin is a promising chemosensitizing agent and that the unique properties of curcumin may be exploited for successful management of resistant tumours.\",\n \"title\": \"Death by design: where curcumin sensitizes drug-resistant tumours.\"\n },\n {\n \"docid\": \"MED-4115\",\n \"text\": \"Cui and associates show that healthy individuals have natural autoantibodies (NAAs) specific for myeloperoxidase, proteinase 3, and glomerular basement membrane (GBM) with the same specificity as anti-neutrophil cytoplasmic antibodies and anti-GBM antibodies that are pathogenic. Although Ehrlich proposed horror autotoxicus and Burnet envisioned elimination of forbidden clones, NAAs are present in all healthy individuals and play beneficial homeostatic roles. Pathogenic autoimmunity is dysregulation of natural homeostatic autoimmunity rather than onset of a previously absent self-recognition.\",\n \"title\": \"The rise and fall of horror autotoxicus and forbidden clones.\"\n },\n {\n \"docid\": \"MED-2580\",\n \"text\": \"Adequate fruit and vegetable intake was suggested to protect against colorectal cancer and colorectal adenomas; however, several recent prospective studies reported no association. We examined the association between fruits and vegetables and adenomatous polyp recurrence in the Polyp Prevention Trial (PPT). The PPT was a low-fat, high-fiber, high-fruit, and vegetable dietary intervention trial of adenoma recurrence, in which there were no differences in the rate of adenoma recurrence in participants in the intervention and control arms of the trial. In this analysis of the entire PPT trial–based cohort, multiple logistic regression analysis was used to estimate the odds ratio (OR) of advanced and nonadvanced adenoma recurrence within quartiles of baseline and change (baseline minus the mean over 3 y) in fruit and vegetable intake, after adjustment for age, total energyy intake, use of nonsteroidal anti-inflammatory drugs, BMI, and gender. There were no significant associations between nonadvanced adenoma recurrence and overall change in fruit and vegetable consumption; however, those in the highest quartile of change in dry bean intake (greatest increase) compared with those in the lowest had a significantly reduced OR for advanced adenoma recurrence (OR = 0.35; 95% CI, 0.18–0.69; P for trend = 0.001). The median in the highest quartile of change in dry bean intake was 370% higher than the baseline intake. The PPT trial–based cohort provides evidence that dry beans may be inversely associated with advanced adenoma recurrence.\",\n \"title\": \"High Dry Bean Intake and Reduced Risk of Advanced Colorectal Adenoma Recurrence among Participants in the Polyp Prevention Trial\"\n },\n {\n \"docid\": \"MED-2823\",\n \"text\": \"Curcumin, the yellow pigment from the rhizoma of Curcuma longa, is a widely studied phytochemical which has a variety of biological activities: anti-inflammatory and anti-oxidative. In this review we discuss the biological mechanisms and possible clinical effects of curcumin treatment on cancer therapy, and neurodegenerative diseases such as Alzheimer's Disease, with particular attention to the cell death processes induced by curcumin. Since oxidative stress and inflammation are major determinants of the aging process, we also argue that curcumin can have a more general effect that slows down the rate of aging. Finally, the effects of curcumin can be described as xenohormetic, since it activates a sort of stress response in mammalian cells.\",\n \"title\": \"Curcumin in Cell Death Processes: A Challenge for CAM of Age-Related Pathologies\"\n },\n {\n \"docid\": \"MED-2607\",\n \"text\": \"Numerous natural compounds have been extensively investigated for their potential for cancer prevention over decades. Curcumin, from Curcuma longa, is a highly promising natural compound that can be potentially used for chemoprevention of multiple cancers. Curcumin modulates multiple molecular pathways involved in the lengthy carcinogenesis process to exert its chemopreventive effects through several mechanisms: promoting apoptosis, inhibiting survival signals, scavenging reactive oxidative species (ROS), and reducing the inflammatory cancer microenvironment. Curcumin fulfills the characteristics for an ideal chemopreventive agent with its low toxicity, affordability, and easy accessibility. Nevertheless, the clinical application of curcumin is currently compromised by its poor bioavailability. Here we review the potential of curcumin in cancer prevention, its molecular targets, and action mechanisms. Finally, we suggest specific recommendations to improve its efficacy and bioavailability for clinical applications.\",\n \"title\": \"New perspectives of curcumin in cancer prevention\"\n },\n {\n \"docid\": \"MED-2799\",\n \"text\": \"Objective: To compare selected immunohistological features of inflammation in synovial tissue from patients with early and late osteoarthritis (OA). Methods: Synovial tissue samples were obtained from 10 patients with knee pain, normal radiographs, and arthroscopic manifestations of OA (early OA), and from 15 patients with OA undergoing knee joint arthroplasty (late OA). Conventional immunohistochemical techniques were used to measure microscopic manifestations of inflammation. The inflammatory cell infiltrate, blood vessel formation, and angiogenic factors, NF-κB activation, expression of tumour necrosis factor α (TNFα) and interleukin 1ß (IL1ß), and the presence of cyclo-oxygenase (COX)-1 and COX-2 were quantified. Fibroblast-like synoviocytes (FLS) were isolated from early and late OA tissue samples to compare in vitro production of prostaglandin E2 (PGE2) Results: Synovial tissue from patients with early OA demonstrated significantly greater CD4+ (p = 0.017) and CD68+ (p<0.001) cell infiltration, blood vessel formation (p = 0.01), vascular endothelial growth factor (p = 0.001), and intercellular adhesion molecule-1 expression (p<0.001). Numbers of cells producing TNFα and IL1ß were also significantly greater in early OA (p<0.001). Manifestations of inflammation in early OA were associated with increased expression of the NF-κB1 (p<0.001) and RelA (p = 0.015) subunits, and with increased COX-2 expression (p = 0.04). Cytokine-induced PGE2 production by cultured FLS was similar in both groups. Conclusion: Increased mononuclear cell infiltration and overexpression of mediators of inflammation were seen in early OA, compared with late OA. Isolated FLS were functionally similar in both groups, consistent with microenvironmental differences in the synovial tissue during different phases of OA. These observations may have important therapeutic implications for some patients during the early evolution of OA.\",\n \"title\": \"Synovial tissue inflammation in early and late osteoarthritis\"\n },\n {\n \"docid\": \"MED-2577\",\n \"text\": \"A case-control study probing the role of diet on the incidence of colorectal cancer was undertaken in Athens, Greece, in a population characterized by ethnic homogeneity but substantial heterogeneity with respect to dietary habits. The case series consisted of 100 consecutive patients with histologically confirmed colorectal cancer admitted to two large hospitals of Athens during a 16-month period; the control series consisted of orthopaedic patients, admitted to the same hospitals during the same time period, individually matched to the index cases by age and sex. Dietary histories concerning the frequency of consumption (per month or per week) of about 80 food items were obtained by the same interviewer. Cases reported significantly less frequent consumption of vegetables (particularly beets, spinach, lettuce and cabbage) and, independently, significantly more frequent consumption of meat (notably lamb and beef). Between the two extremes (high-vegetable, low-meat diet versus high-meat, low-vegetable diet) a risk ratio of about 8 appears to exist, sufficient (in size and direction) to explain a substantial part of the international variation in the incidence of colorectal cancer. Significant associations were not found with beer or other alcoholic beverages, and significant interactions were not noted with respect to age, sex and anatomic localization (colon vs. rectum).\",\n \"title\": \"Diet and colorectal cancer: a case-control study in Greece.\"\n },\n {\n \"docid\": \"MED-2571\",\n \"text\": \"Background Prospective, randomized, pilot clinical study was conducted to evaluate the beneficial effects of inositol hexaphosphate (IP6) + Inositol in breast cancer patients treated with adjuvant therapy. Patients and methods Patients with invasive ductal breast cancer where polychemotherapy was indicated were monitored in the period from 2005-2007. Fourteen patients in the same stage of ductal invasive breast cancer were involved in the study, divided in two randomized groups. One group was subjected to take IP6 + Inositol while the other group was taking placebo. In both groups of patients the same laboratory parameters were monitored. When the treatment was finished, all patients have filled questionnaires QLQ C30 and QLQ-BR23 to determine the quality of life. Results Patients receiving chemotherapy, along with IP6 + Inositol did not have cytopenia, drop in leukocyte and platelet counts. Red blood cell counts and tumor markers were unaltered in both groups. However, patients who took IP6 + Inositol had significantly better quality of life (p = 0.05) and functional status (p = 0.0003) and were able to perform their daily activities. Conclusion IP6 + Inositol as an adjunctive therapy is valuable help in ameliorating the side effects and preserving quality of life among the patients treated with chemotherapy.\",\n \"title\": \"Efficacy of IP6 + inositol in the treatment of breast cancer patients receiving chemotherapy: prospective, randomized, pilot clinical study\"\n },\n {\n \"docid\": \"MED-2811\",\n \"text\": \"Inflammatory bowel disease (IBD) comprising of ulcerative colitis (UC) and Crohn's disease (CD) is a major ailment affecting the small and large bowel. In clinics, IBD is treated using 5-amninosalicylates, antibiotics, the steroids and immunomodulators. Unfortunately, the long term usages of these agents are associated with undue side effects and compromise the therapeutic advantage. Accordingly, there is a need for novel agents that are effective, acceptable and non toxic to humans. Preclinical studies in experimental animals have shown that curcumin, an active principle of the Indian spice turmeric (Curcuma longa Linn) is effective in preventing or ameliorating UC and inflammation. Over the last few decades there has been increasing interest in the possible role of curcumin in IBD and several studies with various experimental models of IBD have shown it to be effective in mediating the inhibitory effects by scavenging free radicals, increasing antioxidants, influencing multiple signaling pathways, especially the kinases (MAPK, ERK), inhibiting myeloperoxidase, COX-1, COX-2, LOX, TNF-α, IFN-γ, iNOS; inhibiting the transcription factor NF-κB. Clinical studies have also shown that co-administration of curcumin with conventional drugs was effective, to be well-tolerated and treated as a safe medication for maintaining remission, to prevent relapse and improve clinical activity index. Large randomized controlled clinical investigations are required to fully understand the potential of oral curcumin for treating IBD.\",\n \"title\": \"Curcumin, an active component of turmeric in the prevention and treatment of ulcerative colitis: preclinical and clinical observations.\"\n },\n {\n \"docid\": \"MED-2818\",\n \"text\": \"Curcumin is a polyphenol derived from the herbal remedy and dietary spice turmeric. It possesses diverse anti-inflammatory and anti-cancer properties following oral or topical administration. Apart from curcumin's potent antioxidant capacity at neutral and acidic pH, its mechanisms of action include inhibition of several cell signalling pathways at multiple levels, effects on cellular enzymes such as cyclooxygenase and glutathione S-transferases, immuno-modulation and effects on angiogenesis and cell-cell adhesion. Curcumin's ability to affect gene transcription and to induce apoptosis in preclinical models is likely to be of particular relevance to cancer chemoprevention and chemotherapy in patients. Although curcumin's low systemic bioavailability following oral dosing may limit access of sufficient concentrations for pharmacological effect in certain tissues, the attainment of biologically active levels in the gastrointestinal tract has been demonstrated in animals and humans. Sufficient data currently exist to advocate phase II clinical evaluation of oral curcumin in patients with invasive malignancy or pre-invasive lesions of the gastrointestinal tract, particularly the colon and rectum.\",\n \"title\": \"Curcumin: the story so far.\"\n },\n {\n \"docid\": \"MED-2792\",\n \"text\": \"Two populations of immigrants to London and to the West Indies from the Indian subcontinent have higher than expected morbidity and mortality from atherosclerosis but do not show the commonly accepted major risk factors. This study investigated the hypothesis that ghee, a clarified butter product prized in Indian cooking, contains cholesterol oxides and could therefore be an important source of dietary exposure to cholesterol oxides and an explanation for the high atherosclerosis risk. Substantial amounts of cholesterol oxides were found in ghee (12.3% of sterols), but not in fresh butter, by thin-layer and high-performance-liquid chromatography. Dietary exposure to cholesterol oxides from ghee may offer a logical explanation for the high frequency of atherosclerotic complications in these Indian populations.\",\n \"title\": \"Cholesterol oxides in Indian ghee: possible cause of unexplained high risk of atherosclerosis in Indian immigrant populations.\"\n },\n {\n \"docid\": \"MED-4390\",\n \"text\": \"The medicinal properties of curcumin obtained from Curcuma longa L. cannot be utilised because of poor bioavailability due to its rapid metabolism in the liver and intestinal wall. In this study, the effect of combining piperine, a known inhibitor of hepatic and intestinal glucuronidation, was evaluated on the bioavailability of curcumin in rats and healthy human volunteers. When curcumin was given alone, in the dose 2 g/kg to rats, moderate serum concentrations were achieved over a period of 4 h. Concomitant administration of piperine 20 mg/kg increased the serum concentration of curcumin for a short period of 1-2 h post drug. Time to maximum was significantly increased (P < 0.02) while elimination half life and clearance significantly decreased (P < 0.02), and the bioavailability was increased by 154%. On the other hand in humans after a dose of 2 g curcumin alone, serum levels were either undetectable or very low. Concomitant administration of piperine 20 mg produced much higher concentrations from 0.25 to 1 h post drug (P < 0.01 at 0.25 and 0.5 h; P < 0.001 at 1 h), the increase in bioavailability was 2000%. The study shows that in the dosages used, piperine enhances the serum concentration, extent of absorption and bioavailability of curcumin in both rats and humans with no adverse effects.\",\n \"title\": \"Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers.\"\n },\n {\n \"docid\": \"MED-2584\",\n \"text\": \"In a 6-year prospective study, the authors examined the relation between diet and incident colon cancer among 32,051 non-Hispanic white cohort members of the Adventist Health Study (California, 1976-1982) who, at baseline, had no documented or reported history of cancer. The risk of colon cancer was determined from proportional hazards regression with adjustment for age and other covariates. The authors found a positive association with total meat intake (risk ratio (RR) for > or =1 time/week vs. no meat intake = 1.85, 95% confidence interval (CI) 1.19-2.87; p for trend = 0.01) and, among subjects who favored specific types of meat, positive associations with red meat intake (RR for > or =1 time/week vs. no red meat intake = 1.90, 95% CI 1.16-3.11; p for trend = 0.02) and white meat intake (RR for > or =1 time/week vs. no white meat intake = 3.29, 95% CI 1.60-6.75; p for trend = 0.006). An inverse association with legume intake (RR for >2 times/week vs. <1 time/week = 0.53, 95% CI 0.33-0.86; p for trend = 0.03) was observed. Among men, a positive association with body mass index was observed (relative to the RR for tertile III (>25.6 kg/m2) vs. tertile I (<22.5 kg/m2) = 2.63, 95% CI 1.12-6.13; p for trend = 0.05). A complex relation was identified whereby subjects exhibiting a high red meat intake, a low legume intake, and a high body mass experienced a more than threefold elevation in risk relative to all other patterns based on these variables. This pattern of putative risk factors would likely contribute to increases in both insulin resistance (high body mass, high red meat intake) and glycemic load (low legume intake), a synergism that, if causal, implicates hyperinsulinemic exposure in colon carcinogenesis. The overall findings from this cohort identify both red meat intake and white meat intake as important dietary risk factors for colon cancer and raise the possibility that the risk due to red meat intake reflects a more complex etiology.\",\n \"title\": \"Dietary risk factors for colon cancer in a low-risk population.\"\n },\n {\n \"docid\": \"MED-2824\",\n \"text\": \"Cancer is primarily a disease of old age, and that life style plays a major role in the development of most cancers is now well recognized. While plant-based formulations have been used to treat cancer for centuries, current treatments usually involve poisonous mustard gas, chemotherapy, radiation, and targeted therapies. While traditional plant-derived medicines are safe, what are the active principles in them and how do they mediate their effects against cancer is perhaps best illustrated by curcumin, a derivative of turmeric used for centuries to treat a wide variety of inflammatory conditions. Curcumin is a diferuloylmethane derived from the Indian spice, turmeric (popularly called \\\"curry powder\\\") that has been shown to interfere with multiple cell signaling pathways, including cell cycle (cyclin D1 and cyclin E), apoptosis (activation of caspases and down-regulation of antiapoptotic gene products), proliferation (HER-2, EGFR, and AP-1), survival (PI3K/AKT pathway), invasion (MMP-9 and adhesion molecules), angiogenesis (VEGF), metastasis (CXCR-4) and inflammation (NF-kappaB, TNF, IL-6, IL-1, COX-2, and 5-LOX). The activity of curcumin reported against leukemia and lymphoma, gastrointestinal cancers, genitourinary cancers, breast cancer, ovarian cancer, head and neck squamous cell carcinoma, lung cancer, melanoma, neurological cancers, and sarcoma reflects its ability to affect multiple targets. Thus an \\\"old-age\\\" disease such as cancer requires an \\\"age-old\\\" treatment.\",\n \"title\": \"Curcumin and cancer: an \\\"old-age\\\" disease with an \\\"age-old\\\" solution.\"\n },\n {\n \"docid\": \"MED-2783\",\n \"text\": \"Although much has been published about curcumin, which is obtained from turmeric, comparatively little is known about turmeric itself. Turmeric, a golden spice obtained from the rhizome of the plant Curcuma longa, has been used to give color and taste to food preparations since ancient times. Traditionally, this spice has been used in Ayurveda and folk medicine for the treatment of such ailments as gynecological problems, gastric problems, hepatic disorders, infectious diseases, and blood disorders. Modern science has provided the scientific basis for the use of turmeric against such disorders. Various chemical constituents have been isolated from this spice, including polyphenols, sesquiterpenes, diterpenes, triterpenoids, sterols, and alkaloids. Curcumin, which constitutes 2-5% of turmeric, is perhaps the most-studied component. Although some of the activities of turmeric can be mimicked by curcumin, other activities are curcumin-independent. Cell-based studies have demonstrated the potential of turmeric as an antimicrobial, insecticidal, larvicidal, antimutagenic, radioprotector, and anticancer agent. Numerous animal studies have shown the potential of this spice against proinflammatory diseases, cancer, neurodegenerative diseases, depression, diabetes, obesity, and atherosclerosis. At the molecular level, this spice has been shown to modulate numerous cell-signaling pathways. In clinical trials, turmeric has shown efficacy against numerous human ailments including lupus nephritis, cancer, diabetes, irritable bowel syndrome, acne, and fibrosis. Thus, a spice originally common in the kitchen is now exhibiting activities in the clinic. In this review, we discuss the chemical constituents of turmeric, its biological activities, its molecular targets, and its potential in the clinic. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.\",\n \"title\": \"Multitargeting by turmeric, the golden spice: From kitchen to clinic.\"\n },\n {\n \"docid\": \"MED-4544\",\n \"text\": \"Emblica officinalis Gaertn. or Phyllanthus emblica Linn, commonly known as Indian gooseberry or amla, is arguably the most important medicinal plant in the Indian traditional system of medicine, the Ayurveda. Various parts of the plant are used to treat a range of diseases, but the most important is the fruit. The fruit is used either alone or in combination with other plants to treat many ailments such as common cold and fever; as a diuretic, laxative, liver tonic, refrigerant, stomachic, restorative, alterative, antipyretic, anti-inflammatory, hair tonic; to prevent peptic ulcer and dyspepsia, and as a digestive. Preclinical studies have shown that amla possesses antipyretic, analgesic, antitussive, antiatherogenic, adaptogenic, cardioprotective, gastroprotective, antianemia, antihypercholesterolemia, wound healing, antidiarrheal, antiatherosclerotic, hepatoprotective, nephroprotective, and neuroprotective properties. In addition, experimental studies have shown that amla and some of its phytochemicals such as gallic acid, ellagic acid, pyrogallol, some norsesquiterpenoids, corilagin, geraniin, elaeocarpusin, and prodelphinidins B1 and B2 also possess antineoplastic effects. Amla is also reported to possess radiomodulatory, chemomodulatory, chemopreventive effects, free radical scavenging, antioxidant, anti-inflammatory, antimutagenic and immunomodulatory activities, properties that are efficacious in the treatment and prevention of cancer. This review for the first time summarizes the results related to these properties and also emphasizes the aspects that warrant future research to establish its activity and utility as a cancer preventive and therapeutic drug in humans.\",\n \"title\": \"Amla (Emblica officinalis Gaertn), a wonder berry in the treatment and prevention of cancer.\"\n },\n {\n \"docid\": \"MED-2801\",\n \"text\": \"Turmeric has been long recognized for its anti-inflammatory and health-promoting properties. Curcumin is one of the principal anti-inflammatory and healthful components of turmeric comprising 2-8% of most turmeric preparations. Experimental evidence supports the activity of curcumin in promoting weight loss and reducing the incidence of obesity-related diseases. With the discovery that obesity is characterized by chronic low-grade metabolic inflammation, phytochemicals like curcumin which have anti-inflammatory activity are being intensely investigated. Recent scientific research reveals that curcumin directly interacts with white adipose tissue to suppress chronic inflammation. In adipose tissue, curcumin inhibits macrophage infiltration and nuclear factor κB (NF-κB) activation induced by inflammatory agents. Curcumin reduces the expression of the potent proinflammatory adipokines tumor necrosis factor-α (TNFα), monocyte chemoattractant protein-1 (MCP-1), and plasminogen activator inhibitor type-1 (PAI-1), and it induces the expression of adiponectin, the principal anti-inflammatory agent secreted by adipocytes. Curcumin also has effects to inhibit adipocyte differentiation and to promote antioxidant activities. Through these diverse mechanisms curcumin reduces obesity and curtails the adverse health effects of obesity. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.\",\n \"title\": \"Curcumin and obesity.\"\n },\n {\n \"docid\": \"MED-2573\",\n \"text\": \"A significant anticancer activity of the naturally occurring carbohydrate inositol hexaphosphate (IP(6)) has been reported against numerous cancer models. Since tumors require angiogenesis for growth and metastasis, we hypothesize that IP(6) reduces tumor growth by inhibiting angiogenesis. Because angiogenesis depends on the interaction between endothelial and tumor cells, we investigated the effect of IP(6) on both. IP(6) inhibited the proliferation and induced the differentiation of endothelial cells in vitro; the growth of bovine aortic endothelial cells (BAECs) evaluated by MTT proliferation assay was inhibited in a dose-dependent manner (IC(50) = 0.74 mM). The combination of IP(6) and vasostatin, a calreticulin fragment with anti-angiogenic activity, was synergistically superior in growth inhibition than either compound. IP(6) inhibited human umbilical vein endothelial cell (HUVEC) tube formation (in vitro capillary differentiation) on a reconstituted extracellular matrix, Matrigel, and disrupted pre-formed tubes. IP(6) significantly reduced basic fibroblast growth factor (bFGF)-induced vessel formation (P < 0.01) in vivo in Matrigel plug assay. Exposure of HepG2, a human hepatoma cell line, to IP(6) for 8 h, resulted in a dose-dependent decrease in the mRNA levels of vascular endothelial growth factor (VEGF), as assessed by RT-PCR. IP(6) treatment of HepG2 cells for 24 h also significantly reduced the VEGF protein levels in conditioned medium, in a concentration-dependent manner (P = 0.012). Thus, IP(6) has an inhibitory effect on induced angiogenesis.\",\n \"title\": \"Anti-angiogenic activity of inositol hexaphosphate (IP6).\"\n },\n {\n \"docid\": \"MED-2988\",\n \"text\": \"This review describes the present state of knowledge about phytic acid (phytate), which is often present in legume seeds. The antinutritional effects of phytic acid primarily relate to the strong chelating associated with its six reactive phosphate groups. Its ability to complex with proteins and particularly with minerals has been a subject of investigation from chemical and nutritional viewpoints. The hydrolysis of phytate into inositol and phosphates or phosphoric acid occurs as a result of phytase or nonenzymatic cleavage. Enzymes capable of hydrolysing phytates are widely distributed in micro-organisms, plants and animals. Phytases act in a stepwise manner to catalyse the hydrolysis of phytic acid. To reduce or eliminate the chelating ability of phytate, dephosphorylation of hexa- and penta-phosphate forms is essential since a high degree of phosphorylation is necessary to bind minerals. There are several methods of decreasing the inhibitory effect of phytic acid on mineral absorption (cooking, germination, fermentation, soaking, autolysis). Nevertheless, inositol hexaphosphate is receiving increased attention owing to its role in cancer prevention and/or therapy and its hypocholesterolaemic effect.\",\n \"title\": \"The role of phytic acid in legumes: antinutrient or beneficial function?\"\n },\n {\n \"docid\": \"MED-2827\",\n \"text\": \"Alternative and complementary therapeutic approaches, such as the use of a wide array of herbal, nutritional, and physical manipulations, are becoming popular for relieving symptoms of osteoarthritis (OA). The present study evaluated the efficacy of soy protein (SP) supplementation in relieving the pain and discomfort associated with OA. One hundred and thirty-five free-living individuals (64 men and 71 women) with diagnosed OA or with self-reported chronic knee joint pain not attributed to injury or rheumatoid arthritis were recruited for this double-blind, placebo-controlled, parallel design study. Study participants were assigned randomly to consume 40 g of either supplemental SP or milk-based protein (MP) daily for 3 months. Pain, knee range of motion, and overall physical activity were evaluated prior to the start of treatment and monthly thereafter. Serum levels of glycoprotein 39 (YKL-40), a marker of cartilage degradation, and insulin-like growth factor-I (IGF-I), a growth factor associated with cartilage synthesis, were assessed at baseline and at the end of the study. Overall, SP improved OA-associated symptoms such as range of motion and several factors associated with pain and quality of life in comparison to MP. However, these beneficial effects were mainly due to the effect of SP in men rather than women. Biochemical markers of cartilage metabolism further support the efficacy of SP in men as indicated by a significant increase in serum level of IGF-I and a significant decrease in serum level of YKL-40 compared to MP. This study is the first to provide evidence of possible beneficial effects of SP in the management of OA. Examining and verifying the long-term effects of SP on improving symptoms of OA, particularly in men, is warranted.\",\n \"title\": \"Soy protein may alleviate osteoarthritis symptoms.\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"MED-1819","text":"Gemcitabine is a first line cancer drug widely used for the treatment of pancreatic cancer. However, its therapeutic efficiency is significantly limited by resistance of pancreatic cancer cells to this and other chemotherapeutic drugs. We have investigated the cytotoxic effect of Turmeric Force (TF), a supercritical and hydroethanolic extract of turmeric, alone and in combination with gemcitabine in two pancreatic carcinoma cell lines (BxPC3 and Panc-1). TF is highly cytotoxic to BxPC3 and Panc-1 cell lines with IC50 values of 1.0 and 1.22 microg/ml, respectively with superior cytotoxicity than curcumin. Gemcitabine IC50 value for both of these cell line is 0.03 microg/ml; however, 30-48% of the pancreatic cancer cells are resistant to gemcitabine even at concentrations >100 microg/ml. In comparison, TF induced cell death in 96% of the cells at 50 microg/ml. The combination of gemcitabine and TF was synergistic with IC90 levels achieved in both pancreatic cancer cell lines at lower concentrations. CalcuSyn analysis of cytotoxicity data showed that the Gemcitabine + Turmeric Force combination has strong synergism with combination index (CI) values of 0.050 and 0.183 in BxPC3 and Panc-1 lines, respectively at IC50 level. This synergistic effect is due to the increased inhibitory effect of the combination on nuclear factor-kappaB activity and signal transducer and activator of transcription factor 3 expression as compared to the single agent.","title":"Potentiation of gemcitabine by Turmeric Force in pancreatic cancer cell lines."},{"docid":"MED-4999","text":"Curcumin (Cur), a component of turmeric (Curcuma longa), has been reported to exhibit antimetastatic activities, but the mechanisms remain unclear. Other curcuminoids present in turmeric, demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC) have not been investigated whether they exhibit antimetastatic activity to the same extent as curcumin. The regulation of matrix metalloproteinases (MMPs) and urokinase plasminogen activator (uPA) play important role in cancer cell invasion by cleavage of extracellular matrix (ECM). In this line, we comparatively examined the influence of Cur, DMC and BDMC on the expressions of uPA, MMP-2, MMP-9, membrane Type 1 MMP (MT1-MMP), tissue inhibitor of metalloproteinases (TIMP-2), and in vitro invasiveness of human fibrosarcoma cells. The results indicate that the differential potency for inhibition of cancer cell invasion was BDMC> or =DMC>Cur, whereas the cell migration was not affected. Zymography analysis exhibited that curcumin, DMC and BDMC significantly decreased uPA, active-MMP-2 and MMP-9 but not pro-MMP-2 secretion from the cells in a dose-dependent manner, in which BDMC and DMC show higher potency than curcumin. The suppression of active MMP-2 level correlated with inhibition of MT1-MMP and TIMP-2 protein levels involved in pro-MMP-2 activation. Importantly, BDMC and DMC at 10 microM reduced MT1-MMP and TIMP-2 protein expression, but curcumin slightly reduced only MT1-MMP but not TIMP-2. In addition, three forms of curcuminoids significantly inhibited collagenase, MMP-2, and MMP-9 but not uPA activity. In summary, these data demonstrated that DMC and BDMC show higher antimetastasis potency than curcumin by the differentially down-regulation of ECM degradation enzymes.","title":"Curcumin, demethoxycurcumin and bisdemethoxycurcumin differentially inhibit cancer cell invasion through the down-regulation of MMPs and uPA."},{"docid":"MED-5001","text":"We examine the possible evidence that the phytochemical curcumin may overcome resistance to hormonal and cytotoxic agents in breast cancer. We present our observations on MCF-7R, a multidrug-resistant (MDR) variant of the MCF-7 breast cancer cell line. In contrast to MCF-7, MCF-7R lacks aromatase and estrogen receptor alpha (ERalpha) and overexpresses the multidrug transporter ABCB1 and the products of different genes implicated in cell proliferation and survival, like c-IAP-1, NAIP, survivin, and COX-2. Nevertheless, in cytotoxicity and cell death induction assays, we found that the antitumor activity of curcumin is substantial both in MCF-7 and in MCF-7R. We elaborated the diketone system of curcumin into different analogues; the benzyloxime and the isoxazole and pyrazole heterocycles showed remarkable increases in the antitumor potency both in the parental and in the MDR MCF-7 cells. Furthermore, curcumin or, more potently, the isoxazole analogue, produced early reductions in the amounts of relevant gene transcripts that were diverse (i.e., they were relative to Bcl-2 and Bcl-X(L) in MCF-7 and the inhibitory of apoptosis proteins and COX-2 in MCF-7R) in the two cell lines. Thus, the two compounds exhibited the remarkable property of being able to modify their molecular activities according to the distinct characteristics of the parental and MDR cells. We discuss also how curcumin may (1) exert antitumor effects in breast cancer through ER-dependent and ER-independent mechanisms; and (2) act as a drug transporter-mediated MDR reversal agent. Overall, the structure of curcumin may represent the basis for the development of new, effective anticancer agents in hormone-independent MDR breast cancer.","title":"Curcumin as a possible lead compound against hormone-independent, multidrug-resistant breast cancer."},{"docid":"MED-2243","text":"An ethanol extract of turmeric (\"Curcuma longa\") as well as an ointment of curcumin (its active ingredient) were found to produce remarkable symptomatic relief in patients with external cancerous lesions. Reduction in smell were noted in 90% of the cases and reduction in itching in almost all cases. Dry lesions were observed in 70% of the cases, and a small number of patients (10%) had a reduction in lesion size and pain. In many patients the effect continued for several months. An adverse reaction was noticed in only one of the 62 patients evaluated.","title":"Turmeric and curcumin as topical agents in cancer therapy."},{"docid":"MED-2239","text":"OBJECTIVE: Human papillomavirus (HPV) infections remain a leading cause of mortality worldwide. In the U.S. strategies via screening and vaccination prevent HPV-associated cervical neoplasms, but consume immense healthcare costs. The spice component curcumin has potent anticancer and antiviral properties, which have been difficult to harness as a treatment, due to its poor systemic bioavailability. This project tests the possibility of developing a curcumin-based therapy for cervical cancer. METHODS: Using four HPV(+) cervical cancer cell lines and normal fibroblasts we first tested the selectivity and potency of curcumin in eliminating HPV(+) cells. Subsequently, we developed a curcumin-based cervical cream and tested its efficacy in eliminating apposed HPV(+) cells and also its possible side effects on the vaginal epithelium of healthy mice. RESULTS: Curcumin selectively eliminates a variety of HPV(+) cervical cancer cells (HeLa, ME-180, SiHa, and SW756), suppresses the transforming antigen E6, dramatically inhibits the expression of the pro-cancer protein epidermal growth factor receptor (EGFR), and concomitantly induces p53. Additionally, Vacurin, a uniform colloidal solution of curcumin in a clinically used amphipathic vaginal cream, eliminates apposed HeLa cells while suppressing the expression of EGFR. In mice, daily intravaginal application of Vacurin for three weeks produced no change in body weight and when the mice were sacrificed, the vaginal tract epithelium showed no Vacurin-evoked adverse effects. CONCLUSION: We have developed a curcumin-based vaginal cream, which effectively eradicates HPV(+) cancer cells and does not affect non-cancerous tissue. Our preclinical data support a novel approach for the treatment of cervical HPV infection. Copyright © 2012 Elsevier Inc. All rights reserved.","title":"A novel curcumin-based vaginal cream Vacurin selectively eliminates apposed human cervical cancer cells."},{"docid":"MED-4998","text":"Curcumin has been reported to have the potential to prevent obesity as well as cancers. The downstream targets regulated by AMP-activated protein kinase (AMPK) for inhibiting adipocyte differentiation or cancer cell proliferation of curcumin were investigated. The activation of AMPK by curcumin was crucial for the inhibition of differentiation or growth in both adipocytes and cancer cells. Stimulation of AMPK by curcumin resulted in the down-regulation of PPAR (peroxisome proliferator-activated receptor)-gamma in 3T3-L1 adipocytes and the decrease in COX-2 in MCF-7 cells. Application of a synthetic AMPK activator also supported the evidence that AMPK acts as an upstream signal of PPAR-gamma in 3T3-L1 adipocytes. In cancer cells, AMPK was found to act as a regulator of ERK1/2, p38, and COX-2. Regulation of AMPK and its downstream targets such as PPAR-gamma, Mapkinases, and COX-2 by curcumin appears to be important in controlling adipocytes and cancerous cells.","title":"Curcumin exerts antidifferentiation effect through AMPKalpha-PPAR-gamma in 3T3-L1 adipocytes and antiproliferatory effect through AMPKalpha-COX-2 i..."},{"docid":"MED-2606","text":"Curcumin, the active principle of turmeric, is known to act as an anti-oxidant, anti-mutagen and anti-carcinogen in experimental animals. In the present study, anti-mutagenic effects of turmeric were assessed in 16 chronic smokers. It was observed that turmeric, given in doses of 1.5 g/day for 30 days, significantly reduced the urinary excretion of mutagens in smokers. In contrast, in six non-smokers, who served as control, there was no change in the urinary excretion of mutagens after 30 days. Turmeric had no significant effect on serum aspartate aminotransferase and alanine aminotransferase, blood glucose, creatinine and lipid profile. These results indicate that dietary turmeric is an effective anti-mutagen and it may be useful in chemoprevention.","title":"Effect of turmeric on urinary mutagens in smokers."},{"docid":"MED-2608","text":"The effects of curcumin, the yellow pigment of the spice, turmeric (Curcuma longa) on the mutagenicity of several environmental mutagens were investigated in the Salmonella/microsome test with or without Aroclor 1254-induced rat-liver homogenate (S-9 mix). With Salmonella typhimurium strain TA98 in the presence of S-9 mix, curcumin inhibited the mutagenicity of bidi and cigarette smoke condensates, tobacco and masheri extracts, benzo[a]pyrne and dimethyl benzo[a]anthracene in a dose-dependent manner. Curcumin did not influence the mutagenicity without S-9 mix of sodium azide, monoacetylhydrazine and streptozocin in strain TA100 nor of 4-nitrophenylenediamine in strain TA98. Our observations indicate that curcumin may alter the metabolic activation and detoxification of mutagens.","title":"In vitro antimutagenicity of curcumin against environmental mutagens."},{"docid":"MED-1507","text":"Vascular endothelial function is declines with aging and is associated with an increased risk of cardiovascular disease. Lifestyle modification, particularly aerobic exercise and dietary adjustment, has a favorable effect on vascular aging. Curcumin is a major component of turmeric with known anti-inflammatory and anti-oxidative effects. We investigated the effects of curcumin ingestion and aerobic exercise training on flow-mediated dilation as an indicator endothelial function in postmenopausal women. A total of 32 postmenopausal women were assigned to 3 groups: control, exercise, and curcumin groups. The curcumin group ingested curcumin orally for 8 weeks. The exercise group underwent moderate aerobic exercise training for 8 weeks. Before and after each intervention, flow-mediated dilation was measured. No difference in baseline flow-mediated dilation or other key dependent variables were detected among the groups. Flow-mediated dilation increased significantly and equally in the curcumin and exercise groups, whereas no changes were observed in the control group. Our results indicated that curcumin ingestion and aerobic exercise training can increase flow-mediated dilation in postmenopausal women, suggesting that both can potentially improve the age-related decline in endothelial function. Copyright © 2012 Elsevier Inc. All rights reserved.","title":"Curcumin ingestion and exercise training improve vascular endothelial function in postmenopausal women."},{"docid":"MED-1813","text":"PURPOSE: Pancreatic cancer is almost always lethal, and the only U.S. Food and Drug Administration-approved therapies for it, gemcitabine and erlotinib, produce objective responses in <10% of patients. We evaluated the clinical biological effects of curcumin (diferuloylmethane), a plant-derived dietary ingredient with potent nuclear factor-kappaB (NF-kappaB) and tumor inhibitory properties, against advanced pancreatic cancer. EXPERIMENTAL DESIGN: Patients received 8 g curcumin by mouth daily until disease progression, with restaging every 2 months. Serum cytokine levels for interleukin (IL)-6, IL-8, IL-10, and IL-1 receptor antagonists and peripheral blood mononuclear cell expression of NF-kappaB and cyclooxygenase-2 were monitored. RESULTS: Twenty-five patients were enrolled, with 21 evaluable for response. Circulating curcumin was detectable as drug in glucuronide and sulfate conjugate forms, albeit at low steady-state levels, suggesting poor oral bioavailability. Two patients showed clinical biological activity. One had ongoing stable disease for >18 months; interestingly, one additional patient had a brief, but marked, tumor regression (73%) accompanied by significant increases (4- to 35-fold) in serum cytokine levels (IL-6, IL-8, IL-10, and IL-1 receptor antagonists). No toxicities were observed. Curcumin down-regulated expression of NF-kappaB, cyclooxygenase-2, and phosphorylated signal transducer and activator of transcription 3 in peripheral blood mononuclear cells from patients (most of whom had baseline levels considerably higher than those found in healthy volunteers). Whereas there was considerable interpatient variation in plasma curcumin levels, drug levels peaked at 22 to 41 ng/mL and remained relatively constant over the first 4 weeks. CONCLUSIONS: Oral curcumin is well tolerated and, despite its limited absorption, has biological activity in some patients with pancreatic cancer.","title":"Phase II trial of curcumin in patients with advanced pancreatic cancer."},{"docid":"MED-2245","text":"Curcumin (diferuloylmethane) is being considered as a potential chemopreventive agent in humans. In vitro it inhibits transcription by NF-kappaB, and the activity of lipoxygenase or cyclooxygenase enzymes, which facilitate tumor progression. In vivo it is protective in rodent models of chemical carcinogenesis. Curcumin contains an alpha,beta-unsaturated ketone, a reactive chemical substituent that is responsible for its repression of NF-kappaB. In compounds other than curcumin this same electrophilic moiety is associated with inactivation of the tumor suppressor, p53. Here we report that curcumin behaves analogously to these compounds. It disrupts the conformation of the p53 protein required for its serine phosphorylation, its binding to DNA, its transactivation of p53-responsive genes and p53-mediated cell cycle arrest.","title":"Curcumin impairs tumor suppressor p53 function in colon cancer cells."},{"docid":"MED-2246","text":"Curcuma spp. extracts, particularly the dietary polyphenol curcumin, prevent colon cancer in rodents. In view of the sparse information on the pharmacodynamics and pharmacokinetics of curcumin in humans, a dose-escalation pilot study of a novel standardized Curcuma extract in proprietary capsule form was performed at doses between 440 and 2200 mg/day, containing 36-180 mg of curcumin. Fifteen patients with advanced colorectal cancer refractory to standard chemotherapies received Curcuma extract daily for up to 4 months. Activity of glutathione S-transferase and levels of a DNA adduct (M(1)G) formed by malondialdehyde, a product of lipid peroxidation and prostaglandin biosynthesis, were measured in patients' blood cells. Oral Curcuma extract was well tolerated, and dose-limiting toxicity was not observed. Neither curcumin nor its metabolites were detected in blood or urine, but curcumin was recovered from feces. Curcumin sulfate was identified in the feces of one patient. Ingestion of 440 mg of Curcuma extract for 29 days was accompanied by a 59% decrease in lymphocytic glutathione S-transferase activity. At higher dose levels, this effect was not observed. Leukocytic M(1)G levels were constant within each patient and unaffected by treatment. Radiologically stable disease was demonstrated in five patients for 2-4 months of treatment. The results suggest that (a) Curcuma extract can be administered safely to patients at doses of up to 2.2 g daily, equivalent to 180 mg of curcumin; (b) curcumin has low oral bioavailability in humans and may undergo intestinal metabolism; and (c) larger clinical trials of Curcuma extract are merited.","title":"Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer."},{"docid":"MED-3724","text":"Drug resistance remains an on-going challenge in ovarian cancer chemotherapy. The objective of this study was to determine the effect on synergism in activity from the sequenced combinations of cisplatin (Cis) with curcumin (Cur) and epigallocatechin-3-gallate (EGCG) in the human ovarian cancer cell lines. The drugs were added in binary combinations: Cis combined with Cur, and Cis combined with EGCG to the human ovarian A2780 and A2780(cisR) cancer cell lines, using five different sequences of administration: 0/0 h, 4/0 h, 0/4 h, 24/0 h and 0/24 h. The combination index (CI) was used to assess the combined action of the drugs. CIs <1, =1 and >1 indicated synergism, additiveness and antagonism respectively. Cellular accumulation of platinum and platinum-DNA binding levels from Cis and its combination with the phytochemicals were determined using graphite furnace atomic absorption spectrometry. Addition of Cis 4 h before Cur and EGCG (0/4 h combination) produced the most synergistic outcomes in both the A2780 and A2780(cisR) cell lines. The cellular accumulations of platinum and platinum-DNA binding resulting from the 0/4 h combinations were greater as compared to the values using Cis alone, thus providing an explanation for the synergistic action. When sequenced combinations of Cis with Cur and with EGCG are applied to human ovarian A2780 and A2780(cisR) cancer cell lines, lower concentrations and shorter time gap between the two additions seem to produce a higher cytotoxic effect.","title":"Synergism from sequenced combinations of curcumin and epigallocatechin-3-gallate with cisplatin in the killing of human ovarian cancer cells."},{"docid":"MED-1112","text":"Because of the central role of the transcription factor nuclear factor-kappaB (NF-kappaB) in cell survival and proliferation in human multiple myeloma (MM), we explored the possibility of using it as a target for MM treatment by using curcumin (diferuloylmethane), an agent known to have very little or no toxicity in humans. We found that NF-kappaB was constitutively active in all human MM cell lines examined and that curcumin, a chemopreventive agent, down-regulated NF-kappaB in all cell lines as indicated by electrophoretic mobility gel shift assay and prevented the nuclear retention of p65 as shown by immunocytochemistry. All MM cell lines showed consitutively active IkappaB kinase (IKK) and IkappaBalpha phosphorylation. Curcumin suppressed the constitutive IkappaBalpha phosphorylation through the inhibition of IKK activity. Curcumin also down-regulated the expression of NF-kappaB-regulated gene products, including IkappaBalpha, Bcl-2, Bcl-x(L), cyclin D1, and interleukin-6. This led to the suppression of proliferation and arrest of cells at the G(1)/S phase of the cell cycle. Suppression of NF-kappaB complex by IKKgamma/NF-kappaB essential modulator-binding domain peptide also suppressed the proliferation of MM cells. Curcumin also activated caspase-7 and caspase-9 and induced polyadenosine-5'-diphosphate-ribose polymerase (PARP) cleavage. Curcumin-induced down-regulation of NF-kappaB, a factor that has been implicated in chemoresistance, also induced chemosensitivity to vincristine and melphalan. Overall, our results indicate that curcumin down-regulates NF-kappaB in human MM cells, leading to the suppression of proliferation and induction of apoptosis, thus providing the molecular basis for the treatment of MM patients with this pharmacologically safe agent.","title":"Curcumin (diferuloylmethane) down-regulates the constitutive activation of nuclear factor-kappa B and IkappaBalpha kinase in human multiple myeloma..."},{"docid":"MED-4461","text":"The objective of this study was to investigate, whether the plant-derived isothiocyanate Sulforaphane (SFN) enhances the antitumor activities of the chemotherapeutic agent oxaliplatin (Ox) in a cell culture model of colorectal cancer. Caco-2 cells were cultured under standard conditions and treated with increasing concentrations of SFN [1-20 μM] and/or Ox [100 nM-10 μM]. For co-incubation, cells were pre-treated with SFN for 24 h. Cell growth was determined by BrdU incorporation. Drug interactions were assessed using the combination-index method (CI) (Cl < 1 indicates synergism). Apoptotic events were characterized by different ELISA techniques. Protein levels were examined by Western blot analysis. Annexin V- and propidium iodide (PI) staining followed by FACS analysis was used to differentiate between apoptotic and necrotic events. SFN and Ox alone inhibited cell growth of Caco-2 cells in a dose-dependent manner, an effect, which could be synergistically enhanced, when cells were incubated with the combination of both agents. Co-treated cells further displayed distinctive morphological changes that occurred during the apoptotic process, such as cell surface exposure of phosphatidylserine, membrane blebbing as well as the occurence of cytoplasmic histone-associated DNA fragments. Further observations thereby pointed toward simultaneous activation of both extrinsic and intrinsic apoptotic pathways. With increasing concentrations and treatment duration, a shift from apoptotic to necrotic cell death could be observed. In conclusion, the data suggest that the isothiocyanate SFN sensitizes colon cancer cells to Ox-induced cell growth inhibition via induction of different modes of cell death.","title":"Sulforaphane potentiates oxaliplatin-induced cell growth inhibition in colorectal cancer cells via induction of different modes of cell death."},{"docid":"MED-2240","text":"Curcumin interacts with a large number of extra- and intracellular targets in a biphasic dose-dependent manner. It controls inflammation, oxidative stress, cell survival, cell secretion, homeostasis, and proliferation. Its mechanisms of action are generally directed toward cells that exhibit disordered physiology or blatant mutation-based abnormal states. Optimizing preventative or therapeutic applications require delivering appropriate quantities of curcumin to lesioned cellular targets. Since diseased conditions anatomically are located from topical to systemic sites, efficient application of curcumin requires specific lesion-oriented delivery methods, representatives of which are here reviewed. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.","title":"Curcumin (diferuloylmethane) delivery methods: a review."},{"docid":"MED-938","text":"Saffron (dried stigmas of Crocus sativus L.) has been used as a spice, food colorant and medicinal plant for millennia. In this study cytotoxic effect of saffron extract was evaluated in HepG2 and HeLa cell lines. Meanwhile role of apoptosis and ROS were explored. Malignant and non-malignant cells (L929) were cultured in DMEM medium and incubated with different concentrations of ethanolic saffron extract. Cell viability was quantitated by MTT assay. Apoptotic cells were determined using PI staining of DNA fragmentation by flow cytometry (sub-G1 peak). ROS was measured using DCF-DA by flow cytometry analysis. Saffron could decrease cell viability in malignant cells as a concentration and time-dependent manner. The IC50 values against HeLa and HepG2 were determined 800 and 950 microg/ml after 48 h, respectively. Saffron induced a sub-G1 peak in flow cytometry histogram of treated cells compared to control indicating apoptotic cell death is involved in saffron toxicity. This toxicity was also independent of ROS production. It might be concluded that saffron could cause cell death in HeLa and HepG2 cells, in which apoptosis or programmed cell death plays an important role. Saffron could be also considered as a promising chemotherapeutic agent in cancer treatment in future.","title":"Study of cytotoxic and apoptogenic properties of saffron extract in human cancer cell lines."},{"docid":"MED-1942","text":"Curcumin, from the curry spice turmeric, has been shown to possess potent antioxidant and antiinflammatory properties and to reduce beta-amyloid and plaque burden in experimental studies, but epidemiologic evidence is lacking. The authors investigated the association between usual curry consumption level and cognitive function in elderly Asians. In a population-based cohort (n = 1,010) of nondemented elderly Asian subjects aged 60-93 years in 2003, the authors compared Mini-Mental State Examination (MMSE) scores for three categories of regular curry consumption, taking into account known sociodemographic, health, and behavioral correlates of MMSE performance. Those who consumed curry \"occasionally\" and \"often or very often\" had significantly better MMSE scores than did subjects who \"never or rarely\" consumed curry. The authors reported tentative evidence of better cognitive performance from curry consumption in nondemented elderly Asians, which should be confirmed in future studies.","title":"Curry consumption and cognitive function in the elderly."},{"docid":"MED-1811","text":"BACKGROUND: A growing number of preclinical studies have demonstrated that curcumin could be a promising anticancer drug; however, poor bioavailability has been the major obstacle for its clinical application. To overcome this problem, we developed a new form of curcumin (Theracurmin) and reported high plasma curcumin levels could be safely achieved after a single administration of Theracurmin in healthy volunteers. In this study, we aimed to evaluate the safety of repetitive administration of Theracurmin in cancer patients. METHODS: Pancreatic or biliary tract cancer patients who failed standard chemotherapy were eligible for this study. Based on our previous pharmacokinetic study, we selected Theracurmin containing 200 mg of curcumin (Level 1) as a starting dose, and the dose was safely escalated to Level 2, which contained 400 mg of curcumin. Theracurmin was orally administered every day with standard gemcitabine-based chemotherapy. In addition to safety and pharmacokinetics data, NF-κB activity, cytokine levels, efficacy, and quality-of-life score were evaluated. RESULTS: Ten patients were assigned to level 1 and six were to level 2. Peak plasma curcumin levels (median) after Theracurmin administration were 324 ng/mL (range, 47-1,029 ng/mL) at Level 1 and 440 ng/mL (range, 179-1,380 ng/mL) at Level 2. No unexpected adverse events were observed and 3 patients safely continued Theracurmin administration for >9 months. CONCLUSIONS: Repetitive systemic exposure to high concentrations of curcumin achieved by Theracurmin did not increase the incidence of adverse events in cancer patients receiving gemcitabine-based chemotherapy.","title":"A phase I study investigating the safety and pharmacokinetics of highly bioavailable curcumin (Theracurmin) in cancer patients."},{"docid":"MED-1110","text":"PURPOSE: To determine the effect of curcumin on plasma cells and osteoclasts in patients with MGUS. EXPERIMENTAL DESIGN: Twenty-six patients with MGUS were recruited into the study and administered 4 grams/day oral curcumin. Blood and urine samples were collected at specified visits after initiating therapy. Full blood count, B2 microglobulin, serum paraprotein, and immunoglobulin electrophoresis (IEPG and EPG) were determined for all patients at each visit. Serum calcium, 25 hydroxyvitamin D3, and bone-specific alkaline phosphatase were determined at baseline only. Urine, as a morning second-void sample, was collected at each visit for urinary N-telopeptide of type I collagen. RESULTS: Our results show that oral curcumin is able to decrease paraprotein load in a select group (i.e., those having a paraprotein level of >20 g/L) of patients with MGUS. Fifty percent (5 of 10) of these patients had a 12% to 30% reduction in their paraprotein levels, while on curcumin therapy. In addition, 27% of patients on curcumin had a >25% decrease in urinary N-telopeptide of type I collagen. CONCLUSION: Due to the possible progression of MGUS to multiple myeloma, the potential role of curcumin as a therapeutic intervention for MGUS patients warrants further investigation.","title":"The potential role of curcumin in patients with monoclonal gammopathy of undefined significance--its effect on paraproteinemia and the urinary N-te..."},{"docid":"MED-2427","text":"Lipid rafts/caveolae are membrane platforms for signaling molecules that regulate various cellular functions, including cell survival. To better understand the role of rafts in tumor progression and therapeutics, we investigated the effect of raft disruption on cell viability and compared raft levels in human cancer cell lines versus their normal counterparts. Here, we report that cholesterol depletion using methyl-β cyclodextrin caused anoikis-like apoptosis, which in A431 cells involved decreased raft levels, Bcl-xL down-regulation, caspase-3 activation, and Akt inactivation regardless of epidermal growth factor receptor activation. Cholesterol repletion replenished rafts on the cell surface and restored Akt activation and cell viability. Moreover, the breast cancer and the prostate cancer cell lines contained more lipid rafts and were more sensitive to cholesterol depletion-induced cell death than their normal counterparts. These results indicate that cancer cells contain increased levels of rafts and suggest a potential use of raft-modulating agents as anti-cancer drugs.","title":"Elevated Levels of Cholesterol-Rich Lipid Rafts in Cancer Cells Are Correlated with Apoptosis Sensitivity Induced by Cholesterol-Depleting Agents"},{"docid":"MED-3947","text":"Hibiscus sabdariffa Linne (Malvaceae), an attractive plant believed to be native to Africa, is cultivated in the Sudan and Eastern Taiwan. Anthocyanins exist widely in many vegetables and fruits. Some reports demonstrated that anthocyanins extracted from H. sabdariffa L., Hibiscus anthocyanins (HAs) (which are a group of natural pigments existing in the dried calyx of H. sabdariffa L.) exhibited antioxidant activity and liver protection. Therefore, in this study, we explored the effect of HAs on human cancer cells. The result showed that HAs could cause cancer cell apoptosis, especially in HL-60 cells. Using flow cytometry, we found that HAs treatment (0-4 mg/ml) markedly induced apoptosis in HL-60 cells in a dose- and time-dependent manner. The result also revealed increased phosphorylation in p38 and c-Jun, cytochrome c release, and expression of tBid, Fas, and FasL in the HAs-treated HL-60 cells. We further used SB203580 (p38 inhibitor), PD98059 (MEK inhibitor), SP600125 (JNK inhibitor), and wortmannin (phosphatidylinositol 3-kinase; PI-3K inhibitor) to evaluate their effect on the HAs-induced HL-60 death. The data showed that only SB203580 had strong potential in inhibiting HL-60 cell apoptosis and related protein expression and phosphorylation. Therefore, we suggested that HAs mediated HL-60 apoptosis via the p38-FasL and Bid pathway. According to these results, HAs could be developed as chemopreventive agents. However, further investigations into the specificity and mechanism(s) of HAs are needed.","title":"Hibiscus anthocyanins rich extract-induced apoptotic cell death in human promyelocytic leukemia cells."},{"docid":"MED-2044","text":"Cancer incidence increases with advancing age. Over 60% of new cancers and 70% of cancer deaths occur in individuals aged 65 years or older. One factor that may contribute to this is immunosenescence - a canopy term that is used to describe age-related declines in the normal functioning of the immune system. There are multiple age-related deficits in both the innate and adaptive systems that may play a role in the increased incidence of cancer. These include decreased NK-cell function, impaired antigen uptake and presentation by monocytes and dendritic cells, an increase in 'inflammaging', a decline in the number of naïve T-cells able to respond to evolving tumor cells, and an increase in functionally exhausted senescent cells. There is consensus that habitual physical exercise can offer protection against certain types of cancer; however the evidence linking immunological mechanisms, exercise, and reduced cancer risk remain tentative. Multiple studies published over the last two decades suggest that exercise can mitigate the deleterious effects of age on immune function, thus increasing anti-cancer immunity. The potential ameliorative effect of exercise on these mechanisms include evidence that physical activity is able to stimulate greater NK-cell activity, enhance antigen-presentation, reduce inflammation, and prevent senescent cell accumulation in the elderly. Here we discuss the role played by the immune system in preventing and controlling cancer and how aging may retard these anti-cancer mechanisms. We also propose a pathway by which exercise-induced alterations in immunosenescence may decrease the incidence of cancer and help improve prognosis in cancer patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.","title":"Can exercise-related improvements in immunity influence cancer prevention and prognosis in the elderly?"},{"docid":"MED-874","text":"BACKGROUND: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent which selectively kills cancer cells with little effect on normal cells. However, TRAIL resistance is widely found in cancer cells. We have previously reported antimetatstatic and antiangiogenic effects of vanillin, a flavoring agent from vanilla. Here we have evaluated the sensitizing effect of vanillin on a TRAIL-resistant human cervical cancer cell line, HeLa. MATERIALS AND METHODS: Cell viability after treatments was determined by the WST-1 cell counting kit. Apoptosis was demonstrated by detection of caspase-3 activation and cleavage of poly (ADP-ribose) polymerase using immunoblot analysis. Effect of treatments on TRAIL signaling pathway and nuclear factor kappaB (FN-kappaB) activation was studied using immunoblot analysis and luciferase reporter assay. RESULTS: Pretreatment of HeLa cells with vanillin enhanced TRAIL-induced cell death through the apoptosis pathway. Vanillin pretreatment inhibited TRAIL-induced phosphorylation of p65 and transcriptional activity of NF-kappaB. CONCLUSION: Vanillin sensitizes HeLa cells to TRAIL-induced apoptosis by inhibiting NF-kappaB activation.","title":"Vanillin enhances TRAIL-induced apoptosis in cancer cells through inhibition of NF-kappaB activation."},{"docid":"MED-865","text":"Prostate cancer remains the second leading cause of cancer deaths among American men. Earlier diagnosis increases survival rate in patients. However, treatments for advanced disease are limited to hormone ablation techniques and palliative care. Thus, new methods of treatment and prevention are necessary for inhibiting disease progression to a hormone refractory state. One of the approaches to control prostate cancer is prevention through diet, which inhibits one or more neoplastic events and reduces the cancer risk. For centuries, Ayurveda has recommended the use of bitter melon (Momordica charantia) as a functional food to prevent and treat human health related issues. In this study, we have initially used human prostate cancer cells, PC3 and LNCaP, as an in vitro model to assess the efficacy of bitter melon extract (BME) as an anti-cancer agent. We observed that prostate cancer cells treated with BME accumulate during the S phase of the cell cycle, and modulate cyclin D1, cyclin E and p21 expression. Treatment of prostate cancer cells with BME enhanced Bax expression, and induced poly(ADP-ribose) polymerase cleavage. Oral gavage of BME, as a dietary compound, delayed the progression to high grade prostatic intraepithelial neoplasia (PIN) in TRAMP (transgenic adenocarcinoma of mouse prostate) mice (31%). Prostate tissue from BME-fed mice displayed ~51% reduction of PCNA expression. Together, our results suggest for the first time that oral administration of BME inhibits prostate cancer progression in TRAMP mice by interfering cell cycle progression and proliferation.","title":"Bitter melon extract impairs prostate cancer cell cycle progression and delays prostatic intraepithelial neoplasia in TRAMP model"},{"docid":"MED-1512","text":"BACKGROUND: Lifestyle modification (i.e., regular physical activity and diet) is effective in preventing the age-related increase in cardiovascular disease risks. Potential therapeutic effects of curcumin (diferuloylmethane) have been confirmed on various diseases, including cancer and Alzheimer's disease, but the effects of curcumin have not been tested on central arterial hemodynamics. The aim of this pilot study was to test the hypothesis that the regular endurance exercise combined with daily curcumin ingestion lowers the age-related increase in left ventricular (LV) afterload to a greater extent than monotherapy with either intervention alone in postmenopausal women using a randomized, double-blind, placebo-controlled, parallel manner. METHODS: Forty-five women were randomly assigned to four interventions: \"placebo ingestion\" (n = 11), \"curcumin ingestion\" (n = 11), \"exercise training with placebo ingestion\" (n = 11), or \"exercise training with curcumin ingestion\" (n = 12). Curcumin or placebo pills (150 mg/day) were administered for 8 weeks. Aortic blood pressure (BP) and augmentation index (AIx), an index of LV afterload, were evaluated by pulse wave analysis from tonometrically measured radial arterial pressure waveforms. RESULTS: There were no significant differences in baseline hemodynamic variables among four groups. After the interventions, brachial systolic BP (SBP) significantly decreased in both exercise-trained groups (P < 0.05 for both), whereas aortic SBP significantly decreased only in the combined-treatment (e.g., exercise and curcumin) group (P < 0.05). Heart rate (HR) corrected aortic AIx significantly decreases only in the combined-treatment group. CONCLUSIONS: These findings suggest that regular endurance exercise combined with daily curcumin ingestion may reduce LV afterload to a greater extent than monotherapy with either intervention alone in postmenopausal women.","title":"Effect of endurance exercise training and curcumin intake on central arterial hemodynamics in postmenopausal women: pilot study."},{"docid":"MED-4711","text":"Licorice is a common Chinese medicinal herb with antitumor activity. Some components in licorice root have been shown to induce cell cycle arrest or apoptosis in cancer cells. This paper demonstrates for the first time that licorice Glycyrrhiza glabra and its component licochalcone-A (LA) can induce autophagy in addition to apoptosis in human LNCaP prostate cancer cells. Exposure of cells to licorice or LA resulted in several confirmed characteristics of autophagy, including the appearance of autophagic vacuoles revealed by monodansylcadaverine (MDC) staining, formation of acidic vesicular organelles (AVOs), and autophagosome membrane association of microtubule-associated protein 1 light chain 3 (LC3) characterized by cleavage of LC3 and its punctuate redistribution, as well as ultrastructural observation of autophagic vacuoles by transmission electron microscopy. Autophagy induction was accompanied by down-regulation of Bcl-2 and inhibition of the mammalian target of rapamycin (mTOR) pathway. In summary, licorice can induce caspase-dependent and autophagy-related cell death in LNCaP cells.","title":"Licorice and licochalcone-A induce autophagy in LNCaP prostate cancer cells by suppression of Bcl-2 expression and the mTOR pathway."},{"docid":"MED-3548","text":"Cancer metastasis refers to the spread of cancer cells from the primary neoplasm to distant sites, where secondary tumors are formed, and is the major cause of death from cancer. Natural phytochemicals containing phenolic compounds have been widely demonstrated to have the capability to prevent cancer metastasis. Among phenolic compounds, flavonoids are a very large subclass, and they are abundant in food and nutraceuticals. The number of reports demonstrating that flavonoids are an effective natural inhibitor of cancer invasion and metastasis is increasing in the scientific literature. Catechin derivatives, (−)-epigallocatechin-3-gallate, (−)-epigallocatechin, (−)-epicatechin-3-gallate,and (−)-epicatechin, are the most studied compounds in this topic so far; genistein/genistin, silibinin, quercetin, and anthocyanin have also been widely investigated for their inhibitory activities on invasion/metastasis. Other flavonoids in dietary vegetable foods that are responsible for anti-invasive and anti-metastatic activities of tumors include luteolin,apigenin, myricetin, tangeretin, kaempferol, glycitein, licoricidin,daidzein, and naringenin. To effectively overcome the metastatic cascade, including cell-cell attachment, tissue barrier degradation, migration, invasion, cell-matrix adhesion,and angiogenesis, it is essential that a bioactive compound prevent tumor cells from metastasizing. This review summarizes the effects of flavonoids on the metastatic cascade and the related proteins, the in vitro anti-invasive activity of flavonoids against cancer cells, and the effects of flavonoids on antiangiogenic and in vivo anti-metastatic models. The available scientific evidence indicates that flavonoids are a ubiquitous dietary phenolics subclass and exert extensive in vitro anti-invasive and in vivo anti-metastatic activities.","title":"Flavonoids, a ubiquitous dietary phenolic subclass, exert extensive in vitro anti-invasive and in vivo anti-metastatic activities."},{"docid":"MED-4907","text":"Tumor metastasis is the most important cause of cancer death and various treatment strategies have targeted on preventing the occurrence of metastasis. Anthocyanins are natural colorants belonging to the flavonoid family, and are wildly used for their antioxidant properties. Here, we provided molecular evidence associated with the anti-metastatic effects of peonidin 3-glucoside and cyanidin 3-glucoside, major anthocyanins extracted from black rice (Oryza sativa L. indica), by showing a marked inhibition on the invasion and motility of SKHep-1 cells. This effect was associated with a reduced expression of matrix metalloproteinase (MMP)-9 and urokinase-type plasminogen activator (u-PA). Peonidin 3-glucoside and cyanidin 3-glucoside also exerted an inhibitory effect on the DNA binding activity and the nuclear translocation of AP-1. Furthermore, these compounds also exerted an inhibitory effect of cell invasion on various cancer cells (SCC-4, Huh-7, and HeLa). Finally, anthocyanins from O. sativa L. indica (OAs) were evidenced by its inhibition on the growth of SKHep-1 cells in vivo.","title":"Black rice anthocyanins inhibit cancer cells invasion via repressions of MMPs and u-PA expression."},{"docid":"MED-2244","text":"BACKGROUND & AIMS: Familialadenomatous polyposis (FAP) is an autosomal-dominant disorder characterized by the development of hundreds of colorectal adenomas and eventual colorectal cancer. Regression of adenomas in this syndrome occurs with the administration of nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors, but these compounds can have considerable side effects. We evaluated the efficacy of the combination of diet-derived nonprescription supplements curcumin and quercetin to regress adenomas in patients with FAP. METHODS: Five FAP patients with prior colectomy (4 with retained rectum and 1 with an ileal anal pouch) received curcumin 480 mg and quercetin 20 mg orally 3 times a day. The number and size of polyps were assessed at baseline and after therapy. The Wilcoxon signed-rank test was used to determine differences in the number and size of polyps. Treatment side effects and medication compliance also were evaluated. RESULTS: All 5 patients had a decreased polyp number and size from baseline after a mean of 6 months of treatment with curcumin and quercetin. The mean percent decrease in the number and size of polyps from baseline was 60.4% (P < .05) and 50.9% (P < .05), respectively. Minimal adverse side effects and no laboratory abnormalities were noted. CONCLUSIONS: The combination of curcumin and quercetin appears to reduce the number and size of ileal and rectal adenomas in patients with FAP without appreciable toxicity. Randomized controlled trials are needed to validate these findings.","title":"Combination treatment with curcumin and quercetin of adenomas in familial adenomatous polyposis."}],"string":"[\n {\n \"docid\": \"MED-1819\",\n \"text\": \"Gemcitabine is a first line cancer drug widely used for the treatment of pancreatic cancer. However, its therapeutic efficiency is significantly limited by resistance of pancreatic cancer cells to this and other chemotherapeutic drugs. We have investigated the cytotoxic effect of Turmeric Force (TF), a supercritical and hydroethanolic extract of turmeric, alone and in combination with gemcitabine in two pancreatic carcinoma cell lines (BxPC3 and Panc-1). TF is highly cytotoxic to BxPC3 and Panc-1 cell lines with IC50 values of 1.0 and 1.22 microg/ml, respectively with superior cytotoxicity than curcumin. Gemcitabine IC50 value for both of these cell line is 0.03 microg/ml; however, 30-48% of the pancreatic cancer cells are resistant to gemcitabine even at concentrations >100 microg/ml. In comparison, TF induced cell death in 96% of the cells at 50 microg/ml. The combination of gemcitabine and TF was synergistic with IC90 levels achieved in both pancreatic cancer cell lines at lower concentrations. CalcuSyn analysis of cytotoxicity data showed that the Gemcitabine + Turmeric Force combination has strong synergism with combination index (CI) values of 0.050 and 0.183 in BxPC3 and Panc-1 lines, respectively at IC50 level. This synergistic effect is due to the increased inhibitory effect of the combination on nuclear factor-kappaB activity and signal transducer and activator of transcription factor 3 expression as compared to the single agent.\",\n \"title\": \"Potentiation of gemcitabine by Turmeric Force in pancreatic cancer cell lines.\"\n },\n {\n \"docid\": \"MED-4999\",\n \"text\": \"Curcumin (Cur), a component of turmeric (Curcuma longa), has been reported to exhibit antimetastatic activities, but the mechanisms remain unclear. Other curcuminoids present in turmeric, demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC) have not been investigated whether they exhibit antimetastatic activity to the same extent as curcumin. The regulation of matrix metalloproteinases (MMPs) and urokinase plasminogen activator (uPA) play important role in cancer cell invasion by cleavage of extracellular matrix (ECM). In this line, we comparatively examined the influence of Cur, DMC and BDMC on the expressions of uPA, MMP-2, MMP-9, membrane Type 1 MMP (MT1-MMP), tissue inhibitor of metalloproteinases (TIMP-2), and in vitro invasiveness of human fibrosarcoma cells. The results indicate that the differential potency for inhibition of cancer cell invasion was BDMC> or =DMC>Cur, whereas the cell migration was not affected. Zymography analysis exhibited that curcumin, DMC and BDMC significantly decreased uPA, active-MMP-2 and MMP-9 but not pro-MMP-2 secretion from the cells in a dose-dependent manner, in which BDMC and DMC show higher potency than curcumin. The suppression of active MMP-2 level correlated with inhibition of MT1-MMP and TIMP-2 protein levels involved in pro-MMP-2 activation. Importantly, BDMC and DMC at 10 microM reduced MT1-MMP and TIMP-2 protein expression, but curcumin slightly reduced only MT1-MMP but not TIMP-2. In addition, three forms of curcuminoids significantly inhibited collagenase, MMP-2, and MMP-9 but not uPA activity. In summary, these data demonstrated that DMC and BDMC show higher antimetastasis potency than curcumin by the differentially down-regulation of ECM degradation enzymes.\",\n \"title\": \"Curcumin, demethoxycurcumin and bisdemethoxycurcumin differentially inhibit cancer cell invasion through the down-regulation of MMPs and uPA.\"\n },\n {\n \"docid\": \"MED-5001\",\n \"text\": \"We examine the possible evidence that the phytochemical curcumin may overcome resistance to hormonal and cytotoxic agents in breast cancer. We present our observations on MCF-7R, a multidrug-resistant (MDR) variant of the MCF-7 breast cancer cell line. In contrast to MCF-7, MCF-7R lacks aromatase and estrogen receptor alpha (ERalpha) and overexpresses the multidrug transporter ABCB1 and the products of different genes implicated in cell proliferation and survival, like c-IAP-1, NAIP, survivin, and COX-2. Nevertheless, in cytotoxicity and cell death induction assays, we found that the antitumor activity of curcumin is substantial both in MCF-7 and in MCF-7R. We elaborated the diketone system of curcumin into different analogues; the benzyloxime and the isoxazole and pyrazole heterocycles showed remarkable increases in the antitumor potency both in the parental and in the MDR MCF-7 cells. Furthermore, curcumin or, more potently, the isoxazole analogue, produced early reductions in the amounts of relevant gene transcripts that were diverse (i.e., they were relative to Bcl-2 and Bcl-X(L) in MCF-7 and the inhibitory of apoptosis proteins and COX-2 in MCF-7R) in the two cell lines. Thus, the two compounds exhibited the remarkable property of being able to modify their molecular activities according to the distinct characteristics of the parental and MDR cells. We discuss also how curcumin may (1) exert antitumor effects in breast cancer through ER-dependent and ER-independent mechanisms; and (2) act as a drug transporter-mediated MDR reversal agent. Overall, the structure of curcumin may represent the basis for the development of new, effective anticancer agents in hormone-independent MDR breast cancer.\",\n \"title\": \"Curcumin as a possible lead compound against hormone-independent, multidrug-resistant breast cancer.\"\n },\n {\n \"docid\": \"MED-2243\",\n \"text\": \"An ethanol extract of turmeric (\\\"Curcuma longa\\\") as well as an ointment of curcumin (its active ingredient) were found to produce remarkable symptomatic relief in patients with external cancerous lesions. Reduction in smell were noted in 90% of the cases and reduction in itching in almost all cases. Dry lesions were observed in 70% of the cases, and a small number of patients (10%) had a reduction in lesion size and pain. In many patients the effect continued for several months. An adverse reaction was noticed in only one of the 62 patients evaluated.\",\n \"title\": \"Turmeric and curcumin as topical agents in cancer therapy.\"\n },\n {\n \"docid\": \"MED-2239\",\n \"text\": \"OBJECTIVE: Human papillomavirus (HPV) infections remain a leading cause of mortality worldwide. In the U.S. strategies via screening and vaccination prevent HPV-associated cervical neoplasms, but consume immense healthcare costs. The spice component curcumin has potent anticancer and antiviral properties, which have been difficult to harness as a treatment, due to its poor systemic bioavailability. This project tests the possibility of developing a curcumin-based therapy for cervical cancer. METHODS: Using four HPV(+) cervical cancer cell lines and normal fibroblasts we first tested the selectivity and potency of curcumin in eliminating HPV(+) cells. Subsequently, we developed a curcumin-based cervical cream and tested its efficacy in eliminating apposed HPV(+) cells and also its possible side effects on the vaginal epithelium of healthy mice. RESULTS: Curcumin selectively eliminates a variety of HPV(+) cervical cancer cells (HeLa, ME-180, SiHa, and SW756), suppresses the transforming antigen E6, dramatically inhibits the expression of the pro-cancer protein epidermal growth factor receptor (EGFR), and concomitantly induces p53. Additionally, Vacurin, a uniform colloidal solution of curcumin in a clinically used amphipathic vaginal cream, eliminates apposed HeLa cells while suppressing the expression of EGFR. In mice, daily intravaginal application of Vacurin for three weeks produced no change in body weight and when the mice were sacrificed, the vaginal tract epithelium showed no Vacurin-evoked adverse effects. CONCLUSION: We have developed a curcumin-based vaginal cream, which effectively eradicates HPV(+) cancer cells and does not affect non-cancerous tissue. Our preclinical data support a novel approach for the treatment of cervical HPV infection. Copyright © 2012 Elsevier Inc. All rights reserved.\",\n \"title\": \"A novel curcumin-based vaginal cream Vacurin selectively eliminates apposed human cervical cancer cells.\"\n },\n {\n \"docid\": \"MED-4998\",\n \"text\": \"Curcumin has been reported to have the potential to prevent obesity as well as cancers. The downstream targets regulated by AMP-activated protein kinase (AMPK) for inhibiting adipocyte differentiation or cancer cell proliferation of curcumin were investigated. The activation of AMPK by curcumin was crucial for the inhibition of differentiation or growth in both adipocytes and cancer cells. Stimulation of AMPK by curcumin resulted in the down-regulation of PPAR (peroxisome proliferator-activated receptor)-gamma in 3T3-L1 adipocytes and the decrease in COX-2 in MCF-7 cells. Application of a synthetic AMPK activator also supported the evidence that AMPK acts as an upstream signal of PPAR-gamma in 3T3-L1 adipocytes. In cancer cells, AMPK was found to act as a regulator of ERK1/2, p38, and COX-2. Regulation of AMPK and its downstream targets such as PPAR-gamma, Mapkinases, and COX-2 by curcumin appears to be important in controlling adipocytes and cancerous cells.\",\n \"title\": \"Curcumin exerts antidifferentiation effect through AMPKalpha-PPAR-gamma in 3T3-L1 adipocytes and antiproliferatory effect through AMPKalpha-COX-2 i...\"\n },\n {\n \"docid\": \"MED-2606\",\n \"text\": \"Curcumin, the active principle of turmeric, is known to act as an anti-oxidant, anti-mutagen and anti-carcinogen in experimental animals. In the present study, anti-mutagenic effects of turmeric were assessed in 16 chronic smokers. It was observed that turmeric, given in doses of 1.5 g/day for 30 days, significantly reduced the urinary excretion of mutagens in smokers. In contrast, in six non-smokers, who served as control, there was no change in the urinary excretion of mutagens after 30 days. Turmeric had no significant effect on serum aspartate aminotransferase and alanine aminotransferase, blood glucose, creatinine and lipid profile. These results indicate that dietary turmeric is an effective anti-mutagen and it may be useful in chemoprevention.\",\n \"title\": \"Effect of turmeric on urinary mutagens in smokers.\"\n },\n {\n \"docid\": \"MED-2608\",\n \"text\": \"The effects of curcumin, the yellow pigment of the spice, turmeric (Curcuma longa) on the mutagenicity of several environmental mutagens were investigated in the Salmonella/microsome test with or without Aroclor 1254-induced rat-liver homogenate (S-9 mix). With Salmonella typhimurium strain TA98 in the presence of S-9 mix, curcumin inhibited the mutagenicity of bidi and cigarette smoke condensates, tobacco and masheri extracts, benzo[a]pyrne and dimethyl benzo[a]anthracene in a dose-dependent manner. Curcumin did not influence the mutagenicity without S-9 mix of sodium azide, monoacetylhydrazine and streptozocin in strain TA100 nor of 4-nitrophenylenediamine in strain TA98. Our observations indicate that curcumin may alter the metabolic activation and detoxification of mutagens.\",\n \"title\": \"In vitro antimutagenicity of curcumin against environmental mutagens.\"\n },\n {\n \"docid\": \"MED-1507\",\n \"text\": \"Vascular endothelial function is declines with aging and is associated with an increased risk of cardiovascular disease. Lifestyle modification, particularly aerobic exercise and dietary adjustment, has a favorable effect on vascular aging. Curcumin is a major component of turmeric with known anti-inflammatory and anti-oxidative effects. We investigated the effects of curcumin ingestion and aerobic exercise training on flow-mediated dilation as an indicator endothelial function in postmenopausal women. A total of 32 postmenopausal women were assigned to 3 groups: control, exercise, and curcumin groups. The curcumin group ingested curcumin orally for 8 weeks. The exercise group underwent moderate aerobic exercise training for 8 weeks. Before and after each intervention, flow-mediated dilation was measured. No difference in baseline flow-mediated dilation or other key dependent variables were detected among the groups. Flow-mediated dilation increased significantly and equally in the curcumin and exercise groups, whereas no changes were observed in the control group. Our results indicated that curcumin ingestion and aerobic exercise training can increase flow-mediated dilation in postmenopausal women, suggesting that both can potentially improve the age-related decline in endothelial function. Copyright © 2012 Elsevier Inc. All rights reserved.\",\n \"title\": \"Curcumin ingestion and exercise training improve vascular endothelial function in postmenopausal women.\"\n },\n {\n \"docid\": \"MED-1813\",\n \"text\": \"PURPOSE: Pancreatic cancer is almost always lethal, and the only U.S. Food and Drug Administration-approved therapies for it, gemcitabine and erlotinib, produce objective responses in <10% of patients. We evaluated the clinical biological effects of curcumin (diferuloylmethane), a plant-derived dietary ingredient with potent nuclear factor-kappaB (NF-kappaB) and tumor inhibitory properties, against advanced pancreatic cancer. EXPERIMENTAL DESIGN: Patients received 8 g curcumin by mouth daily until disease progression, with restaging every 2 months. Serum cytokine levels for interleukin (IL)-6, IL-8, IL-10, and IL-1 receptor antagonists and peripheral blood mononuclear cell expression of NF-kappaB and cyclooxygenase-2 were monitored. RESULTS: Twenty-five patients were enrolled, with 21 evaluable for response. Circulating curcumin was detectable as drug in glucuronide and sulfate conjugate forms, albeit at low steady-state levels, suggesting poor oral bioavailability. Two patients showed clinical biological activity. One had ongoing stable disease for >18 months; interestingly, one additional patient had a brief, but marked, tumor regression (73%) accompanied by significant increases (4- to 35-fold) in serum cytokine levels (IL-6, IL-8, IL-10, and IL-1 receptor antagonists). No toxicities were observed. Curcumin down-regulated expression of NF-kappaB, cyclooxygenase-2, and phosphorylated signal transducer and activator of transcription 3 in peripheral blood mononuclear cells from patients (most of whom had baseline levels considerably higher than those found in healthy volunteers). Whereas there was considerable interpatient variation in plasma curcumin levels, drug levels peaked at 22 to 41 ng/mL and remained relatively constant over the first 4 weeks. CONCLUSIONS: Oral curcumin is well tolerated and, despite its limited absorption, has biological activity in some patients with pancreatic cancer.\",\n \"title\": \"Phase II trial of curcumin in patients with advanced pancreatic cancer.\"\n },\n {\n \"docid\": \"MED-2245\",\n \"text\": \"Curcumin (diferuloylmethane) is being considered as a potential chemopreventive agent in humans. In vitro it inhibits transcription by NF-kappaB, and the activity of lipoxygenase or cyclooxygenase enzymes, which facilitate tumor progression. In vivo it is protective in rodent models of chemical carcinogenesis. Curcumin contains an alpha,beta-unsaturated ketone, a reactive chemical substituent that is responsible for its repression of NF-kappaB. In compounds other than curcumin this same electrophilic moiety is associated with inactivation of the tumor suppressor, p53. Here we report that curcumin behaves analogously to these compounds. It disrupts the conformation of the p53 protein required for its serine phosphorylation, its binding to DNA, its transactivation of p53-responsive genes and p53-mediated cell cycle arrest.\",\n \"title\": \"Curcumin impairs tumor suppressor p53 function in colon cancer cells.\"\n },\n {\n \"docid\": \"MED-2246\",\n \"text\": \"Curcuma spp. extracts, particularly the dietary polyphenol curcumin, prevent colon cancer in rodents. In view of the sparse information on the pharmacodynamics and pharmacokinetics of curcumin in humans, a dose-escalation pilot study of a novel standardized Curcuma extract in proprietary capsule form was performed at doses between 440 and 2200 mg/day, containing 36-180 mg of curcumin. Fifteen patients with advanced colorectal cancer refractory to standard chemotherapies received Curcuma extract daily for up to 4 months. Activity of glutathione S-transferase and levels of a DNA adduct (M(1)G) formed by malondialdehyde, a product of lipid peroxidation and prostaglandin biosynthesis, were measured in patients' blood cells. Oral Curcuma extract was well tolerated, and dose-limiting toxicity was not observed. Neither curcumin nor its metabolites were detected in blood or urine, but curcumin was recovered from feces. Curcumin sulfate was identified in the feces of one patient. Ingestion of 440 mg of Curcuma extract for 29 days was accompanied by a 59% decrease in lymphocytic glutathione S-transferase activity. At higher dose levels, this effect was not observed. Leukocytic M(1)G levels were constant within each patient and unaffected by treatment. Radiologically stable disease was demonstrated in five patients for 2-4 months of treatment. The results suggest that (a) Curcuma extract can be administered safely to patients at doses of up to 2.2 g daily, equivalent to 180 mg of curcumin; (b) curcumin has low oral bioavailability in humans and may undergo intestinal metabolism; and (c) larger clinical trials of Curcuma extract are merited.\",\n \"title\": \"Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer.\"\n },\n {\n \"docid\": \"MED-3724\",\n \"text\": \"Drug resistance remains an on-going challenge in ovarian cancer chemotherapy. The objective of this study was to determine the effect on synergism in activity from the sequenced combinations of cisplatin (Cis) with curcumin (Cur) and epigallocatechin-3-gallate (EGCG) in the human ovarian cancer cell lines. The drugs were added in binary combinations: Cis combined with Cur, and Cis combined with EGCG to the human ovarian A2780 and A2780(cisR) cancer cell lines, using five different sequences of administration: 0/0 h, 4/0 h, 0/4 h, 24/0 h and 0/24 h. The combination index (CI) was used to assess the combined action of the drugs. CIs <1, =1 and >1 indicated synergism, additiveness and antagonism respectively. Cellular accumulation of platinum and platinum-DNA binding levels from Cis and its combination with the phytochemicals were determined using graphite furnace atomic absorption spectrometry. Addition of Cis 4 h before Cur and EGCG (0/4 h combination) produced the most synergistic outcomes in both the A2780 and A2780(cisR) cell lines. The cellular accumulations of platinum and platinum-DNA binding resulting from the 0/4 h combinations were greater as compared to the values using Cis alone, thus providing an explanation for the synergistic action. When sequenced combinations of Cis with Cur and with EGCG are applied to human ovarian A2780 and A2780(cisR) cancer cell lines, lower concentrations and shorter time gap between the two additions seem to produce a higher cytotoxic effect.\",\n \"title\": \"Synergism from sequenced combinations of curcumin and epigallocatechin-3-gallate with cisplatin in the killing of human ovarian cancer cells.\"\n },\n {\n \"docid\": \"MED-1112\",\n \"text\": \"Because of the central role of the transcription factor nuclear factor-kappaB (NF-kappaB) in cell survival and proliferation in human multiple myeloma (MM), we explored the possibility of using it as a target for MM treatment by using curcumin (diferuloylmethane), an agent known to have very little or no toxicity in humans. We found that NF-kappaB was constitutively active in all human MM cell lines examined and that curcumin, a chemopreventive agent, down-regulated NF-kappaB in all cell lines as indicated by electrophoretic mobility gel shift assay and prevented the nuclear retention of p65 as shown by immunocytochemistry. All MM cell lines showed consitutively active IkappaB kinase (IKK) and IkappaBalpha phosphorylation. Curcumin suppressed the constitutive IkappaBalpha phosphorylation through the inhibition of IKK activity. Curcumin also down-regulated the expression of NF-kappaB-regulated gene products, including IkappaBalpha, Bcl-2, Bcl-x(L), cyclin D1, and interleukin-6. This led to the suppression of proliferation and arrest of cells at the G(1)/S phase of the cell cycle. Suppression of NF-kappaB complex by IKKgamma/NF-kappaB essential modulator-binding domain peptide also suppressed the proliferation of MM cells. Curcumin also activated caspase-7 and caspase-9 and induced polyadenosine-5'-diphosphate-ribose polymerase (PARP) cleavage. Curcumin-induced down-regulation of NF-kappaB, a factor that has been implicated in chemoresistance, also induced chemosensitivity to vincristine and melphalan. Overall, our results indicate that curcumin down-regulates NF-kappaB in human MM cells, leading to the suppression of proliferation and induction of apoptosis, thus providing the molecular basis for the treatment of MM patients with this pharmacologically safe agent.\",\n \"title\": \"Curcumin (diferuloylmethane) down-regulates the constitutive activation of nuclear factor-kappa B and IkappaBalpha kinase in human multiple myeloma...\"\n },\n {\n \"docid\": \"MED-4461\",\n \"text\": \"The objective of this study was to investigate, whether the plant-derived isothiocyanate Sulforaphane (SFN) enhances the antitumor activities of the chemotherapeutic agent oxaliplatin (Ox) in a cell culture model of colorectal cancer. Caco-2 cells were cultured under standard conditions and treated with increasing concentrations of SFN [1-20 μM] and/or Ox [100 nM-10 μM]. For co-incubation, cells were pre-treated with SFN for 24 h. Cell growth was determined by BrdU incorporation. Drug interactions were assessed using the combination-index method (CI) (Cl < 1 indicates synergism). Apoptotic events were characterized by different ELISA techniques. Protein levels were examined by Western blot analysis. Annexin V- and propidium iodide (PI) staining followed by FACS analysis was used to differentiate between apoptotic and necrotic events. SFN and Ox alone inhibited cell growth of Caco-2 cells in a dose-dependent manner, an effect, which could be synergistically enhanced, when cells were incubated with the combination of both agents. Co-treated cells further displayed distinctive morphological changes that occurred during the apoptotic process, such as cell surface exposure of phosphatidylserine, membrane blebbing as well as the occurence of cytoplasmic histone-associated DNA fragments. Further observations thereby pointed toward simultaneous activation of both extrinsic and intrinsic apoptotic pathways. With increasing concentrations and treatment duration, a shift from apoptotic to necrotic cell death could be observed. In conclusion, the data suggest that the isothiocyanate SFN sensitizes colon cancer cells to Ox-induced cell growth inhibition via induction of different modes of cell death.\",\n \"title\": \"Sulforaphane potentiates oxaliplatin-induced cell growth inhibition in colorectal cancer cells via induction of different modes of cell death.\"\n },\n {\n \"docid\": \"MED-2240\",\n \"text\": \"Curcumin interacts with a large number of extra- and intracellular targets in a biphasic dose-dependent manner. It controls inflammation, oxidative stress, cell survival, cell secretion, homeostasis, and proliferation. Its mechanisms of action are generally directed toward cells that exhibit disordered physiology or blatant mutation-based abnormal states. Optimizing preventative or therapeutic applications require delivering appropriate quantities of curcumin to lesioned cellular targets. Since diseased conditions anatomically are located from topical to systemic sites, efficient application of curcumin requires specific lesion-oriented delivery methods, representatives of which are here reviewed. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.\",\n \"title\": \"Curcumin (diferuloylmethane) delivery methods: a review.\"\n },\n {\n \"docid\": \"MED-938\",\n \"text\": \"Saffron (dried stigmas of Crocus sativus L.) has been used as a spice, food colorant and medicinal plant for millennia. In this study cytotoxic effect of saffron extract was evaluated in HepG2 and HeLa cell lines. Meanwhile role of apoptosis and ROS were explored. Malignant and non-malignant cells (L929) were cultured in DMEM medium and incubated with different concentrations of ethanolic saffron extract. Cell viability was quantitated by MTT assay. Apoptotic cells were determined using PI staining of DNA fragmentation by flow cytometry (sub-G1 peak). ROS was measured using DCF-DA by flow cytometry analysis. Saffron could decrease cell viability in malignant cells as a concentration and time-dependent manner. The IC50 values against HeLa and HepG2 were determined 800 and 950 microg/ml after 48 h, respectively. Saffron induced a sub-G1 peak in flow cytometry histogram of treated cells compared to control indicating apoptotic cell death is involved in saffron toxicity. This toxicity was also independent of ROS production. It might be concluded that saffron could cause cell death in HeLa and HepG2 cells, in which apoptosis or programmed cell death plays an important role. Saffron could be also considered as a promising chemotherapeutic agent in cancer treatment in future.\",\n \"title\": \"Study of cytotoxic and apoptogenic properties of saffron extract in human cancer cell lines.\"\n },\n {\n \"docid\": \"MED-1942\",\n \"text\": \"Curcumin, from the curry spice turmeric, has been shown to possess potent antioxidant and antiinflammatory properties and to reduce beta-amyloid and plaque burden in experimental studies, but epidemiologic evidence is lacking. The authors investigated the association between usual curry consumption level and cognitive function in elderly Asians. In a population-based cohort (n = 1,010) of nondemented elderly Asian subjects aged 60-93 years in 2003, the authors compared Mini-Mental State Examination (MMSE) scores for three categories of regular curry consumption, taking into account known sociodemographic, health, and behavioral correlates of MMSE performance. Those who consumed curry \\\"occasionally\\\" and \\\"often or very often\\\" had significantly better MMSE scores than did subjects who \\\"never or rarely\\\" consumed curry. The authors reported tentative evidence of better cognitive performance from curry consumption in nondemented elderly Asians, which should be confirmed in future studies.\",\n \"title\": \"Curry consumption and cognitive function in the elderly.\"\n },\n {\n \"docid\": \"MED-1811\",\n \"text\": \"BACKGROUND: A growing number of preclinical studies have demonstrated that curcumin could be a promising anticancer drug; however, poor bioavailability has been the major obstacle for its clinical application. To overcome this problem, we developed a new form of curcumin (Theracurmin) and reported high plasma curcumin levels could be safely achieved after a single administration of Theracurmin in healthy volunteers. In this study, we aimed to evaluate the safety of repetitive administration of Theracurmin in cancer patients. METHODS: Pancreatic or biliary tract cancer patients who failed standard chemotherapy were eligible for this study. Based on our previous pharmacokinetic study, we selected Theracurmin containing 200 mg of curcumin (Level 1) as a starting dose, and the dose was safely escalated to Level 2, which contained 400 mg of curcumin. Theracurmin was orally administered every day with standard gemcitabine-based chemotherapy. In addition to safety and pharmacokinetics data, NF-κB activity, cytokine levels, efficacy, and quality-of-life score were evaluated. RESULTS: Ten patients were assigned to level 1 and six were to level 2. Peak plasma curcumin levels (median) after Theracurmin administration were 324 ng/mL (range, 47-1,029 ng/mL) at Level 1 and 440 ng/mL (range, 179-1,380 ng/mL) at Level 2. No unexpected adverse events were observed and 3 patients safely continued Theracurmin administration for >9 months. CONCLUSIONS: Repetitive systemic exposure to high concentrations of curcumin achieved by Theracurmin did not increase the incidence of adverse events in cancer patients receiving gemcitabine-based chemotherapy.\",\n \"title\": \"A phase I study investigating the safety and pharmacokinetics of highly bioavailable curcumin (Theracurmin) in cancer patients.\"\n },\n {\n \"docid\": \"MED-1110\",\n \"text\": \"PURPOSE: To determine the effect of curcumin on plasma cells and osteoclasts in patients with MGUS. EXPERIMENTAL DESIGN: Twenty-six patients with MGUS were recruited into the study and administered 4 grams/day oral curcumin. Blood and urine samples were collected at specified visits after initiating therapy. Full blood count, B2 microglobulin, serum paraprotein, and immunoglobulin electrophoresis (IEPG and EPG) were determined for all patients at each visit. Serum calcium, 25 hydroxyvitamin D3, and bone-specific alkaline phosphatase were determined at baseline only. Urine, as a morning second-void sample, was collected at each visit for urinary N-telopeptide of type I collagen. RESULTS: Our results show that oral curcumin is able to decrease paraprotein load in a select group (i.e., those having a paraprotein level of >20 g/L) of patients with MGUS. Fifty percent (5 of 10) of these patients had a 12% to 30% reduction in their paraprotein levels, while on curcumin therapy. In addition, 27% of patients on curcumin had a >25% decrease in urinary N-telopeptide of type I collagen. CONCLUSION: Due to the possible progression of MGUS to multiple myeloma, the potential role of curcumin as a therapeutic intervention for MGUS patients warrants further investigation.\",\n \"title\": \"The potential role of curcumin in patients with monoclonal gammopathy of undefined significance--its effect on paraproteinemia and the urinary N-te...\"\n },\n {\n \"docid\": \"MED-2427\",\n \"text\": \"Lipid rafts/caveolae are membrane platforms for signaling molecules that regulate various cellular functions, including cell survival. To better understand the role of rafts in tumor progression and therapeutics, we investigated the effect of raft disruption on cell viability and compared raft levels in human cancer cell lines versus their normal counterparts. Here, we report that cholesterol depletion using methyl-β cyclodextrin caused anoikis-like apoptosis, which in A431 cells involved decreased raft levels, Bcl-xL down-regulation, caspase-3 activation, and Akt inactivation regardless of epidermal growth factor receptor activation. Cholesterol repletion replenished rafts on the cell surface and restored Akt activation and cell viability. Moreover, the breast cancer and the prostate cancer cell lines contained more lipid rafts and were more sensitive to cholesterol depletion-induced cell death than their normal counterparts. These results indicate that cancer cells contain increased levels of rafts and suggest a potential use of raft-modulating agents as anti-cancer drugs.\",\n \"title\": \"Elevated Levels of Cholesterol-Rich Lipid Rafts in Cancer Cells Are Correlated with Apoptosis Sensitivity Induced by Cholesterol-Depleting Agents\"\n },\n {\n \"docid\": \"MED-3947\",\n \"text\": \"Hibiscus sabdariffa Linne (Malvaceae), an attractive plant believed to be native to Africa, is cultivated in the Sudan and Eastern Taiwan. Anthocyanins exist widely in many vegetables and fruits. Some reports demonstrated that anthocyanins extracted from H. sabdariffa L., Hibiscus anthocyanins (HAs) (which are a group of natural pigments existing in the dried calyx of H. sabdariffa L.) exhibited antioxidant activity and liver protection. Therefore, in this study, we explored the effect of HAs on human cancer cells. The result showed that HAs could cause cancer cell apoptosis, especially in HL-60 cells. Using flow cytometry, we found that HAs treatment (0-4 mg/ml) markedly induced apoptosis in HL-60 cells in a dose- and time-dependent manner. The result also revealed increased phosphorylation in p38 and c-Jun, cytochrome c release, and expression of tBid, Fas, and FasL in the HAs-treated HL-60 cells. We further used SB203580 (p38 inhibitor), PD98059 (MEK inhibitor), SP600125 (JNK inhibitor), and wortmannin (phosphatidylinositol 3-kinase; PI-3K inhibitor) to evaluate their effect on the HAs-induced HL-60 death. The data showed that only SB203580 had strong potential in inhibiting HL-60 cell apoptosis and related protein expression and phosphorylation. Therefore, we suggested that HAs mediated HL-60 apoptosis via the p38-FasL and Bid pathway. According to these results, HAs could be developed as chemopreventive agents. However, further investigations into the specificity and mechanism(s) of HAs are needed.\",\n \"title\": \"Hibiscus anthocyanins rich extract-induced apoptotic cell death in human promyelocytic leukemia cells.\"\n },\n {\n \"docid\": \"MED-2044\",\n \"text\": \"Cancer incidence increases with advancing age. Over 60% of new cancers and 70% of cancer deaths occur in individuals aged 65 years or older. One factor that may contribute to this is immunosenescence - a canopy term that is used to describe age-related declines in the normal functioning of the immune system. There are multiple age-related deficits in both the innate and adaptive systems that may play a role in the increased incidence of cancer. These include decreased NK-cell function, impaired antigen uptake and presentation by monocytes and dendritic cells, an increase in 'inflammaging', a decline in the number of naïve T-cells able to respond to evolving tumor cells, and an increase in functionally exhausted senescent cells. There is consensus that habitual physical exercise can offer protection against certain types of cancer; however the evidence linking immunological mechanisms, exercise, and reduced cancer risk remain tentative. Multiple studies published over the last two decades suggest that exercise can mitigate the deleterious effects of age on immune function, thus increasing anti-cancer immunity. The potential ameliorative effect of exercise on these mechanisms include evidence that physical activity is able to stimulate greater NK-cell activity, enhance antigen-presentation, reduce inflammation, and prevent senescent cell accumulation in the elderly. Here we discuss the role played by the immune system in preventing and controlling cancer and how aging may retard these anti-cancer mechanisms. We also propose a pathway by which exercise-induced alterations in immunosenescence may decrease the incidence of cancer and help improve prognosis in cancer patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.\",\n \"title\": \"Can exercise-related improvements in immunity influence cancer prevention and prognosis in the elderly?\"\n },\n {\n \"docid\": \"MED-874\",\n \"text\": \"BACKGROUND: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent which selectively kills cancer cells with little effect on normal cells. However, TRAIL resistance is widely found in cancer cells. We have previously reported antimetatstatic and antiangiogenic effects of vanillin, a flavoring agent from vanilla. Here we have evaluated the sensitizing effect of vanillin on a TRAIL-resistant human cervical cancer cell line, HeLa. MATERIALS AND METHODS: Cell viability after treatments was determined by the WST-1 cell counting kit. Apoptosis was demonstrated by detection of caspase-3 activation and cleavage of poly (ADP-ribose) polymerase using immunoblot analysis. Effect of treatments on TRAIL signaling pathway and nuclear factor kappaB (FN-kappaB) activation was studied using immunoblot analysis and luciferase reporter assay. RESULTS: Pretreatment of HeLa cells with vanillin enhanced TRAIL-induced cell death through the apoptosis pathway. Vanillin pretreatment inhibited TRAIL-induced phosphorylation of p65 and transcriptional activity of NF-kappaB. CONCLUSION: Vanillin sensitizes HeLa cells to TRAIL-induced apoptosis by inhibiting NF-kappaB activation.\",\n \"title\": \"Vanillin enhances TRAIL-induced apoptosis in cancer cells through inhibition of NF-kappaB activation.\"\n },\n {\n \"docid\": \"MED-865\",\n \"text\": \"Prostate cancer remains the second leading cause of cancer deaths among American men. Earlier diagnosis increases survival rate in patients. However, treatments for advanced disease are limited to hormone ablation techniques and palliative care. Thus, new methods of treatment and prevention are necessary for inhibiting disease progression to a hormone refractory state. One of the approaches to control prostate cancer is prevention through diet, which inhibits one or more neoplastic events and reduces the cancer risk. For centuries, Ayurveda has recommended the use of bitter melon (Momordica charantia) as a functional food to prevent and treat human health related issues. In this study, we have initially used human prostate cancer cells, PC3 and LNCaP, as an in vitro model to assess the efficacy of bitter melon extract (BME) as an anti-cancer agent. We observed that prostate cancer cells treated with BME accumulate during the S phase of the cell cycle, and modulate cyclin D1, cyclin E and p21 expression. Treatment of prostate cancer cells with BME enhanced Bax expression, and induced poly(ADP-ribose) polymerase cleavage. Oral gavage of BME, as a dietary compound, delayed the progression to high grade prostatic intraepithelial neoplasia (PIN) in TRAMP (transgenic adenocarcinoma of mouse prostate) mice (31%). Prostate tissue from BME-fed mice displayed ~51% reduction of PCNA expression. Together, our results suggest for the first time that oral administration of BME inhibits prostate cancer progression in TRAMP mice by interfering cell cycle progression and proliferation.\",\n \"title\": \"Bitter melon extract impairs prostate cancer cell cycle progression and delays prostatic intraepithelial neoplasia in TRAMP model\"\n },\n {\n \"docid\": \"MED-1512\",\n \"text\": \"BACKGROUND: Lifestyle modification (i.e., regular physical activity and diet) is effective in preventing the age-related increase in cardiovascular disease risks. Potential therapeutic effects of curcumin (diferuloylmethane) have been confirmed on various diseases, including cancer and Alzheimer's disease, but the effects of curcumin have not been tested on central arterial hemodynamics. The aim of this pilot study was to test the hypothesis that the regular endurance exercise combined with daily curcumin ingestion lowers the age-related increase in left ventricular (LV) afterload to a greater extent than monotherapy with either intervention alone in postmenopausal women using a randomized, double-blind, placebo-controlled, parallel manner. METHODS: Forty-five women were randomly assigned to four interventions: \\\"placebo ingestion\\\" (n = 11), \\\"curcumin ingestion\\\" (n = 11), \\\"exercise training with placebo ingestion\\\" (n = 11), or \\\"exercise training with curcumin ingestion\\\" (n = 12). Curcumin or placebo pills (150 mg/day) were administered for 8 weeks. Aortic blood pressure (BP) and augmentation index (AIx), an index of LV afterload, were evaluated by pulse wave analysis from tonometrically measured radial arterial pressure waveforms. RESULTS: There were no significant differences in baseline hemodynamic variables among four groups. After the interventions, brachial systolic BP (SBP) significantly decreased in both exercise-trained groups (P < 0.05 for both), whereas aortic SBP significantly decreased only in the combined-treatment (e.g., exercise and curcumin) group (P < 0.05). Heart rate (HR) corrected aortic AIx significantly decreases only in the combined-treatment group. CONCLUSIONS: These findings suggest that regular endurance exercise combined with daily curcumin ingestion may reduce LV afterload to a greater extent than monotherapy with either intervention alone in postmenopausal women.\",\n \"title\": \"Effect of endurance exercise training and curcumin intake on central arterial hemodynamics in postmenopausal women: pilot study.\"\n },\n {\n \"docid\": \"MED-4711\",\n \"text\": \"Licorice is a common Chinese medicinal herb with antitumor activity. Some components in licorice root have been shown to induce cell cycle arrest or apoptosis in cancer cells. This paper demonstrates for the first time that licorice Glycyrrhiza glabra and its component licochalcone-A (LA) can induce autophagy in addition to apoptosis in human LNCaP prostate cancer cells. Exposure of cells to licorice or LA resulted in several confirmed characteristics of autophagy, including the appearance of autophagic vacuoles revealed by monodansylcadaverine (MDC) staining, formation of acidic vesicular organelles (AVOs), and autophagosome membrane association of microtubule-associated protein 1 light chain 3 (LC3) characterized by cleavage of LC3 and its punctuate redistribution, as well as ultrastructural observation of autophagic vacuoles by transmission electron microscopy. Autophagy induction was accompanied by down-regulation of Bcl-2 and inhibition of the mammalian target of rapamycin (mTOR) pathway. In summary, licorice can induce caspase-dependent and autophagy-related cell death in LNCaP cells.\",\n \"title\": \"Licorice and licochalcone-A induce autophagy in LNCaP prostate cancer cells by suppression of Bcl-2 expression and the mTOR pathway.\"\n },\n {\n \"docid\": \"MED-3548\",\n \"text\": \"Cancer metastasis refers to the spread of cancer cells from the primary neoplasm to distant sites, where secondary tumors are formed, and is the major cause of death from cancer. Natural phytochemicals containing phenolic compounds have been widely demonstrated to have the capability to prevent cancer metastasis. Among phenolic compounds, flavonoids are a very large subclass, and they are abundant in food and nutraceuticals. The number of reports demonstrating that flavonoids are an effective natural inhibitor of cancer invasion and metastasis is increasing in the scientific literature. Catechin derivatives, (−)-epigallocatechin-3-gallate, (−)-epigallocatechin, (−)-epicatechin-3-gallate,and (−)-epicatechin, are the most studied compounds in this topic so far; genistein/genistin, silibinin, quercetin, and anthocyanin have also been widely investigated for their inhibitory activities on invasion/metastasis. Other flavonoids in dietary vegetable foods that are responsible for anti-invasive and anti-metastatic activities of tumors include luteolin,apigenin, myricetin, tangeretin, kaempferol, glycitein, licoricidin,daidzein, and naringenin. To effectively overcome the metastatic cascade, including cell-cell attachment, tissue barrier degradation, migration, invasion, cell-matrix adhesion,and angiogenesis, it is essential that a bioactive compound prevent tumor cells from metastasizing. This review summarizes the effects of flavonoids on the metastatic cascade and the related proteins, the in vitro anti-invasive activity of flavonoids against cancer cells, and the effects of flavonoids on antiangiogenic and in vivo anti-metastatic models. The available scientific evidence indicates that flavonoids are a ubiquitous dietary phenolics subclass and exert extensive in vitro anti-invasive and in vivo anti-metastatic activities.\",\n \"title\": \"Flavonoids, a ubiquitous dietary phenolic subclass, exert extensive in vitro anti-invasive and in vivo anti-metastatic activities.\"\n },\n {\n \"docid\": \"MED-4907\",\n \"text\": \"Tumor metastasis is the most important cause of cancer death and various treatment strategies have targeted on preventing the occurrence of metastasis. Anthocyanins are natural colorants belonging to the flavonoid family, and are wildly used for their antioxidant properties. Here, we provided molecular evidence associated with the anti-metastatic effects of peonidin 3-glucoside and cyanidin 3-glucoside, major anthocyanins extracted from black rice (Oryza sativa L. indica), by showing a marked inhibition on the invasion and motility of SKHep-1 cells. This effect was associated with a reduced expression of matrix metalloproteinase (MMP)-9 and urokinase-type plasminogen activator (u-PA). Peonidin 3-glucoside and cyanidin 3-glucoside also exerted an inhibitory effect on the DNA binding activity and the nuclear translocation of AP-1. Furthermore, these compounds also exerted an inhibitory effect of cell invasion on various cancer cells (SCC-4, Huh-7, and HeLa). Finally, anthocyanins from O. sativa L. indica (OAs) were evidenced by its inhibition on the growth of SKHep-1 cells in vivo.\",\n \"title\": \"Black rice anthocyanins inhibit cancer cells invasion via repressions of MMPs and u-PA expression.\"\n },\n {\n \"docid\": \"MED-2244\",\n \"text\": \"BACKGROUND & AIMS: Familialadenomatous polyposis (FAP) is an autosomal-dominant disorder characterized by the development of hundreds of colorectal adenomas and eventual colorectal cancer. Regression of adenomas in this syndrome occurs with the administration of nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors, but these compounds can have considerable side effects. We evaluated the efficacy of the combination of diet-derived nonprescription supplements curcumin and quercetin to regress adenomas in patients with FAP. METHODS: Five FAP patients with prior colectomy (4 with retained rectum and 1 with an ileal anal pouch) received curcumin 480 mg and quercetin 20 mg orally 3 times a day. The number and size of polyps were assessed at baseline and after therapy. The Wilcoxon signed-rank test was used to determine differences in the number and size of polyps. Treatment side effects and medication compliance also were evaluated. RESULTS: All 5 patients had a decreased polyp number and size from baseline after a mean of 6 months of treatment with curcumin and quercetin. The mean percent decrease in the number and size of polyps from baseline was 60.4% (P < .05) and 50.9% (P < .05), respectively. Minimal adverse side effects and no laboratory abnormalities were noted. CONCLUSIONS: The combination of curcumin and quercetin appears to reduce the number and size of ileal and rectal adenomas in patients with FAP without appreciable toxicity. Randomized controlled trials are needed to validate these findings.\",\n \"title\": \"Combination treatment with curcumin and quercetin of adenomas in familial adenomatous polyposis.\"\n }\n]"}}},{"rowIdx":180,"cells":{"query_id":{"kind":"string","value":"7640"},"query":{"kind":"string","value":"What happens when a company stops trading? (pink sheets)"},"positive_passages":{"kind":"list like","value":[{"docid":"350095","text":"\"What will happen if the stock price just continues to decline? Nothing. What would happen if folks just stop trading it? Nothing. What if the company goes private? Then they will have to buy you out based on some agreed upon price, as voted by the board and (potentially) approved by the shareholders. Depending on the corporation charter, the board may not be required to seek the shareholders' approval, but if the price the board agreed upon is unreasonable you can sue and prevent the transaction. How do they decide the fair value of the outstanding stocks? Through a process called \"\"valuation\"\", there are accounting firms which specialize in this area of public accounting.\"","title":""}],"string":"[\n {\n \"docid\": \"350095\",\n \"text\": \"\\\"What will happen if the stock price just continues to decline? Nothing. What would happen if folks just stop trading it? Nothing. What if the company goes private? Then they will have to buy you out based on some agreed upon price, as voted by the board and (potentially) approved by the shareholders. Depending on the corporation charter, the board may not be required to seek the shareholders' approval, but if the price the board agreed upon is unreasonable you can sue and prevent the transaction. How do they decide the fair value of the outstanding stocks? Through a process called \\\"\\\"valuation\\\"\\\", there are accounting firms which specialize in this area of public accounting.\\\"\",\n \"title\": \"\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"278889","text":"\"Changing my answer based on clarification in comments. It appears that some of the securities you mentioned, including GEAPP, are traded on what is colloquially known as the Grey Market. Grey Sheets, and also known as the \"\"Gray Market\"\" is another category of OTC stocks that is completely separate from Pink Sheets and the OTCBB. From investopedia The grey market is an over-the-counter market where dealers may execute orders for preferred customers as well as provide support for a new issue before it is actually issued. This activity allows underwriters and the issuer to determine demand and price the securities accordingly before the IPO. Some additional information on this type of stocks. (Source) Unlike other financial markets... No recent bid or ask quotes are available because no market makers share data or quote such stocks. There is no quoting system available to record and settle trades. All Grey sheet trading is moderated by a broker and done between consenting individuals at a price they agree on. The only documentation that can be publicly found regarding the trades is when the last trade took place. No SEC registration and little SEC regulation. Regulation of Grey Sheet stocks takes place mainly on a state level. Unlike Pink Sheets, these stocks have no SEC registration to possess a stock symbol or to possess shares or trade shares of that stock. Such penny stocks, similar to Pink Sheets, are not required to file SEC (Securities and Exchange Commission) financial and business reports. These stocks may not be solicited or advertised to the public unless a certain number of shares are qualified to be traded publicly under 504 of Regulation D. Extremely Illiquid. Gray sheet trading is infrequent, and for good reason... Difficult to trade, not advertised, difficult to follow the price, the least regulation possible, hard to find any information on the stock, very small market cap, little history, and most such stocks do not yet offer public shares. The lack of information (bids, history, financial reports) alone causes most investors to be very skeptical of Gray Sheets and avoid them altogether. Gray Sheets are commonly associated with Initial public offering (IPO) stocks or start up companies or spin-off companies, even though not all are IPO's, start-ups or spin-offs. Grey Sheets is also Home to delisted stocks from other markets. Some stocks on this financial market were once traded on the NASDAQ, OTCBB, or the Pink Sheets but ran into serious misfortune - usually financial - and thus failed to meet the minimum requirements of the registered SEC filings and/or stock exchange regulations for a financial market. Such stocks were delisted or removed and may begin trading on the Grey Sheets. So to answer your question, I think the cause of the wild swings is that: Great question, BTW.\"","title":""},{"docid":"107227","text":"popularity that you are referring to is just known as liquidity when discussing markets. More liquid securities tend to trade more shares per day and have very tight bid/ask spreads as many investors are buying and selling the shares at one time. Some larger securities, especially on exchanges, further enhance liquidity by providing market makers. These are individuals on the NYSE, for example, that will make the market in large securities by handling large orders and providing liquidity through their own book of capital. The individuals on the floor on the NYSE you often see on TV are those market makers. However, as trading becomes more electronic, market markers are becoming less and less required. A previous comment suggested pink sheets are risky companies. This is not entirely factual. While the majority of pink sheets are very highly risky companies, many very solid international companies trade their ADRs (American Depository Receipt) on the pink sheets to avoid the high cost of setting up a large exchange at the NYSE and register and report through the SEC. As a TD Ameritrade user, I would be willing to help you out if you have any other questions.","title":""},{"docid":"261640","text":"\"The penny/pink sheet stocks you tend to see promoted are the ones a) with small public floats or, b) they are thinly traded. This means that any appreciable change in buy/sell volume will have an outsized effect on the stock's share price, even when the underlying fundamentals are not so great. Promoters are frequently paid based on how much they can move a stock's price, but such moves are not long-lasting. They peter out when the trading volumes return to more normal ranges for the stock because all of the hype has died out. There are some small-cap NASDAQ stocks which can be susceptible to promotion for the same reason -- they have small floats and/or are thinly traded. Once someone figures out the best targets, they'll accumulate a position and then start posting all kinds of \"\"news\"\" on the web in an effort to drum up interest so they can sell off their position into the buying that follows. The biggest problem with penny/pink sheet stocks is that they frequently fail to publish reliable financial statements, and their ownership is of a dubious nature. In the past, these types of stocks have been targeted by organized crime syndicates, which ran their own \"\"pump and dump\"\" operations as a way to make relatively easy money. This may still be true to some extent today. Be wary of investing in any publicly-traded firm that has to use promoters to drum up investor interest, because it can be a serious red flag. Even if it means missing out on a short-term opportunity, research the company before investing. Read its financials, understand how it has behaved through its trading history, learn about the products/services it is selling. Do your homework. Otherwise you are doing the investing equivalent of taking your money and lighting it on fire. Remember, there's a good reason these companies are trading as penny/pink sheet stocks, and it generally has nothing to do with the notion (the promoters will tell you) that somehow the \"\"market has missed out on this amazing opportunity.\"\" Pump and dump schemes, which lie at the heart of almost all stock promotion, rely on convincing you, the investor, that you're smart enough to see what others haven't. I hope this helps. Good luck!\"","title":""},{"docid":"510163","text":"\"The Minnesota Mining and Manufacturing Company was established in 1902 as a private company. It first raised public funds around 1903 but had a limited shareholder base. By around 1929, it was reported as being tradeable as an OTC (over-the-counter) stock but it's likely that shares were traded well before this. On 14 Jan 1946, the stock was listed on NYSE. On 26 Sep 1962 it became a constituent of the the S&P 500 index. On 9 Aug 1976 it became a constituent of the Dow Jones Industrial Average. In 2002, the company's name changed to 3M Co. It appears that the data on Crunchbase's \"\"IPO Date\"\" is wrong on this one. However, there are several companies that appear to do an \"\"IPO\"\" and have trading prices prior. This is quite typical of early-stage biotech companies that trade OTC prior to a major exchange listing and \"\"IPO\"\". An example of an IPO happening after a company became publicly tradeable is NASDAQ:IMRN (Immuron). They had an \"\"IPO\"\" on Nasdaq on 9 Jun 2017, yet they had been trading as an OTC/Pink Sheet stock for months prior. They also have been listed in Australia since 30 Apr 1999. http://www.nasdaq.com/markets/ipos/activity.aspx?tab=pricings&month=2017-06 Another example is NASDAQ:GNTY (Guaranty Banchshares Inc) which had an \"\"IPO\"\" and NASDAQ listing in May 2017. This was a Nasdaq stock in 1998, went OTC/pink sheet stock in 2005. It has been paying regular dividends since that time. Clearly the word \"\"Initial\"\" is subjective! http://www.nasdaq.com/markets/ipos/activity.aspx?tab=pricings&month=2017-05\"","title":""},{"docid":"165973","text":"It depends on what site you're looking on and what exchange they're pulling the data from. Even though funds and stocks are called the same thing, they have different ticker symbols in each country's exchange or could be traded as pink sheet stocks in the US. If a company or fund is based in another country (like Canada or the UK) they probably also trade on that country's exchange (Toronto or London) under a different symbol. This can cause a lot of confusion when researching these tickers.","title":""},{"docid":"253847","text":"While most all Canadian brokers allow us access to all the US stocks, the reverse is not true. But some US brokers DO allow trading on foreign exchanges. (e.g. Interactive Brokers at which I have an account). You have to look and be prepared to switch brokers. Americans cannot use Canadian brokers (and vice versa). Trading of shares happens where-ever two people get together - hence the pink sheets. These work well for Americans who want to buy-sell foreign stocks using USD without the hassle of FX conversions. You get the same economic exposure as if the actual stock were bought. But the exchanges are barely policed, and liquidity can dry up, and FX moves are not necessarily arbitraged away by 'the market'. You don't have the same safety as ADRs because there is no bank holding any stash of 'actual' stocks to backstop those traded on the pink sheets.","title":""},{"docid":"291903","text":"\"Pink Sheets is not a stock exchange per se, and securities traded through it are not as \"\"safe\"\" as the ones on a stock exchange regulated by SEC. Many companies are traded there because they failed to comply with the SEC regulations, or are bankrupt or don't want the level of reporting to the public that the SEC regulations require. Since you're talking about an ADR of a company traded on LSE, it might be much safer that other, \"\"regular\"\", securities, but still it means that you're buying an unregulated security (even if it is of a company regulated elsewhere). Notice the volume of trades: mere thousands of dollars per day (in a good day, in some days there are no trades at all). It makes it harder to sell the security when needed. Why not buying at LSE?\"","title":""},{"docid":"54257","text":"\"If you own 1% of a company, you are technically entitled to 1% of the current value and future profits of that company. However, you cannot, as you seem to imply, just decide at some point to take your ball and go home. You cannot call up the company and ask for 1% of their assets to be liquidated and given to you in cash. What the 1% stake in the company actually entitles you to is: 1% of total shareholder voting rights. Your \"\"aye\"\" or \"\"nay\"\" carries the weight of 1% of the total shareholder voting block. Doesn't sound like much, but when the average little guy has on the order of ten-millionths of a percentage point ownership of any big corporation, your one vote carries more weight than those of millions of single-share investors. 1% of future dividend payments made to shareholders. For every dollar the corporation makes in profits, and doesn't retain for future growth, you get a penny. Again, doesn't sound like much, but consider that the Simon property group, ranked #497 on the Fortune 500 list of the world's biggest companies by revenue, made $1.4 billion in profits last year. 1% of that, if the company divvied it all up, is $14 million. If you bought your 1% stake in March of 2009, you would have paid a paltry $83 million, and be earning roughly 16% on your initial investment annually just in dividends (to say nothing of the roughly 450% increase in stock price since that time, making the value of your holdings roughly $460 million; that does reduce your actual dividend yield to about 3% of holdings value). If this doesn't sound appealing, and you want out, you would sell your 1% stake. The price you would get for this total stake may or may not be 1% of the company's book value. This is for many reasons: Now, to answer your hypothetical: If Apple's stock, tomorrow, went from $420b market cap to zero, that would mean that the market unanimously thought, when they woke up tomorrow morning, that the company was all of a sudden absolutely worthless. In order to have this unanimous consent, the market must be thoroughly convinced, by looking at SEC filings of assets, liabilities and profits, listening to executive statements, etc that an investor wouldn't see even one penny returned of any cash investment made in this company's stock. That's impossible; the price of a share is based on what someone will pay to have it (or accept to be rid of it). Nobody ever just gives stock away for free on the trading floor, so even if they're selling 10 shares for a penny, they're selling it, and so the stock has a value ($0.001/share). We can say, however, that a fall to \"\"effectively zero\"\" is possible, because they've happened. Enron, for instance, lost half its share value in just one week in mid-October as the scope of the accounting scandal started becoming evident. That was just the steepest part of an 18-month fall from $90/share in August '00, to just $0.12/share as of its bankruptcy filing in Dec '01; a 99.87% loss of value. Now, this is an extreme example, but it illustrates what would be necessary to get a stock to go all the way to zero (if indeed it ever really could). Enron's stock wasn't delisted until a month and a half after Enron's bankruptcy filing, it was done based on NYSE listing rules (the stock had been trading at less than a dollar for 30 days), and was still traded \"\"over the counter\"\" on the Pink Sheets after that point. Enron didn't divest all its assets until 2006, and the company still exists (though its mission is now to sue other companies that had a hand in the fraud, get the money and turn it around to Enron creditors). I don't know when it stopped becoming a publicly-traded company (if indeed it ever did), but as I said, there is always someone willing to buy a bunch of really cheap shares to try and game the market (buying shares reduces the number available for sale, reducing supply, increasing price, making the investor a lot of money assuming he can offload them quickly enough).\"","title":""},{"docid":"454465","text":"If you are trying to invest in closely held / private companies (things that don't trade on the stock market), you will run into a variety of regulatory problems. For various reasons, most private companies only raise funds with accredited investors. To be an accredited investor you basically have to have $1,000,000 in net worth - NOT including your primary residence, OR you have to make over $200,000 a year for the last two years and expect to keep making that much. This is a class distinction the Federal government created, you will see different but similar wealth and investment classes worldwide. So your best most organized opportunities are left out, unless you do qualify as an accredited investor. There are tons of other companies, things you will find locally, that will let you invest in their smaller time operations. (Think like a local yoga studio looking for $20,000 and willing to split the profits with you). But the problem here is lack of accountability, where partners skip town or just stop answering your calls, and the legal remedies cost you more than your claim. That being said there are people that provide capital to smaller publicly traded companies on the bulletin boards and pink sheets. They have opportunities do much better than the actual stock market investors in these companies, because you can negotiate contracts that let you cash out in their inevitable financing death spirals with very little risk to you. You can do these things as an individual or as a holding company, but the holding company will limit your liability to the amount your holding company invested, instead of your personal assets, in case your financing starts to incur liability with the company.","title":""},{"docid":"404936","text":"Depends on the structure of the company and what shares are outstanding. If the pink sheet stock has no voting power then buying all that stock doesn't get you any control at all. On the other hand, if the outstanding shares only represent 20% of the company's overall shares, then buying all the shares isn't likely enough to have a controlling interest. Thus, you'll have to dig into the details. If you want an example of where I'd have my doubts, look at Nestle's stock which has the ticker of NSRGY. There can be companies that are structured with stock on multiple exchanges that can also be a challenge at times. There is also something to be said if you own enough stock in a company that this has to be disclosed to the SEC when you buy more.","title":""},{"docid":"319599","text":"Well I'm not going to advise whether it's a good idea to invest in this company (though often OTC is pretty scary), but it DOES have a product (vivio, an ad blocker), it did post financials and it's trading on the OTC-QB (which is better than the pink sheets), so you need to look these over and study up on the product to decide if it is overpriced or not. What might have occurred (viz the Patriot Berry Farm becoming Cyberfort) is that the latter bought up the stock of the former (this is, I believe, called using a shell, which is not necessarily a bad thing) and is using this as a way to be registered, i.e. sell to non-accredited investors via the OTC market. So I'm really just answering your third question: yes, you have to do a lot of due diligence to see if buying this stock is a good deal or not. It might be the next big thing. Or it might not. It certainly is the case that low trading volume allows a relatively small trade to really change the stock price, so the penny stocks do tend to be easier to 'inflate'. Side comment: the bid/ask spreads are pretty big, with a best bid of 0.35 and best ask of 0.44.","title":""},{"docid":"110584","text":"For the lazy, Wikipedia says: The term microcap stock (also micro-cap) refers to the stock of public companies in the United States which have a market capitalization of roughly $300 million or less. The shares of companies with a market capitalization of less than $50 million are typically referred to as nano-cap stocks. Many micro-cap and nano-cap stocks are traded over-the-counter with their prices quoted on the OTCBB or the Pink Sheets. A few of the larger, more established microcaps are listed on the NASDAQ Capital Market or American Stock Exchange (AMEX). Micro-cap and especially nano-cap stocks are notorious for their volatility. A high percentage of these companies fail to execute their business plans and go out of business. Fraud and market manipulation are not uncommon, and the transactions costs in trading can be quite high. Pricing is more likely to be inefficient, since fewer institutional investors and analysts operate in this space, due to the relatively small dollar amounts involved and the lack of liquidity.","title":""},{"docid":"495255","text":"I'd call it pretty worrisome. HOOB is trading over the counter, in fact, on the pink sheets, so it has been delisted from the major exchanges. It appears that it lacks recent financial disclosures. You'll have to investigate to see if you think it's worth keeping, but trading is thin.","title":""},{"docid":"555047","text":"I traded futures for a brief period in school using the BrokersXpress platform (now part of OptionsXpress, which is in turn now part of Charles Schwab). They had a virtual trading platform, and apparently still do, and it was excellent. Since my main account was enabled for futures, this carried over to the virtual account, so I could trade a whole range of futures, options, stocks, etc. I spoke with OptionsXpress, and you don't need to fund your acount to use the virtual trading platform. However, they will cancel your account after an arbitrary period of time if you don't log in every few days. According to their customer service, there is no inactivity fee on your main account if you don't fund it and make no trades. I also used Stock-Trak for a class and despite finding the occasional bug or website performance issue, it provided a good experience. I received a discount because I used it through an educational institution, and customer service was quite good (probably for the same reason), but I don't know if those same benefits would apply to an individual signing up for it. I signed up for top10traders about seven years ago when I was in secondary school, and it's completely free. Unfortunately, you get what you pay for, and the interface was poorly designed and slow. Furthermore, at that time, there were no restrictions that limited the number of shares you could buy to the number of outstanding shares, so you could buy as many as you could afford, even if you exceeded the number that physically existed. While this isn't an issue for large companies, it meant you could earn a killing trading highly illiquid pink sheet stocks because you could purchase billions of shares of companies with only a few thousand shares actually outstanding. I don't know if these issues have been corrected or not, but at the time, I and several other users took advantage of these oversights to rack up hundreds of trillions of dollars in a matter of days, so if you want a realistic simulation, this isn't it. Investopedia also has a stock simulator that I've heard positive things about, although I haven't used it personally.","title":""},{"docid":"390779","text":"\"The assumption that companies listed OTC are not serious is far from the truth. Many companies on the OTC are just starting off there because they don't meet the requirements to be listed on the NASDAQ or NYSE. Major stock exchanges like the NASDAQ and the NYSE only want the best companies to trade on their exchanges.The NASDAQ, for example, has three sets of listing requirements. A company must meet at least one of the three requirement sets, as well as the main rules for all companies. These include: Now don't assume that the OTC doesn't have rules either, as this is far from the truth as well. While there are no minimum level of revenue, profits or assets required to get listed on the OTC there are requirements for audited financial statements and ongoing filing and reporting to the SEC and NASD. Additionally there are several different levels of the OTC, including the OTCQX, the OTCCB and the OTC Pink, each with their own set of requirements. For more information about what it takes to be listed on OTC look here: http://www.otcmarkets.com/learn/otc-trading A company deciding to trade on the OTC is making the decision to take their company public, and they are investing to make it happen. Currently the fees to get listed on the OTC range from $30,000 to $150,000 depending on the firm you decide to go with and the services they offer as part as their package. Now, I know I wouldn't consider $30K (or more) to not be serious money! When I looked into the process of getting a company listed on the TSX the requirements seemed a lot more relaxed than those of the major U.S. markets as well, consisting of an application, records submission and then a decision made by a TSX committee about whether you get listed. More information about the TSX here: http://apps.tmx.com/en/listings/listing_with_us/process/index.html I think the way that the OTC markets have gotten such a bad reputation is from these \"\"Get Rich on Penny Stock\"\" companies that you see pumping up OTC company stocks and getting massive amounts of people to buy without doing their due diligence and investigating the company and reading its prospectus. Then when they loose a bunch of money on an ill-informed investment decision they blame it on the company being an OTC stock. Whether you decide to trade the OTC market or not, I wouldn't make a decision based on how many exchanges the company is listed on, but rather based on the research you do into the company.\"","title":""},{"docid":"129481","text":"I'm going to guess that you found this because of a stock screener. This company went through a 1:20 reverse split on June 30, so every 20 shares outstanding became a single share. Where before you had 20 shares worth $100 you now have 1 share worth $100, the value of the company doesn't change because of a split. This company was never trading for $30+ per share. Reverse splits are typical of a floundering company trading on an exchange that has a minimum share price requirement. While reverse splits don't change the value of the company, just the number of shares outstanding and the price per share, no healthy company performs a reverse split. Reverse splits are generally a massive signal to jump ship... The company seems to be trading for $1 right now, why the value fell from a pre-split $1.65 ($33/20) to $1 is anyone's guess; how the company ever got to $1.65 is also anyone's guess. But looking at the most recent 10-Q there are numerous causes for concern: Note 2. Capital Stock On March 6, 2017, the Company issued as compensation for services provided a total of 650,000 common shares with a fair value of $390,000 to a third party. The fair value of the shares was based on the price quoted on the OTC pink sheets on the grant date. this indicates a share price of $0.60 ($390,000/650,000) as of 3/6/2017, just to reinforce that the google price chart doesn't show the true past but a past adjusted for the split Results of Operations The three months ended March 31, 2017 compared to the three months ended March 31, 2016 For the three months ended March 31, 2017 compared to the three months ended March 31, 2016, total revenues were $0 and $0, respectively, and net losses from operations were $414,663 and $26,260, respectively. The net losses were attributable to costs attributable to operating as a public company, in particular, common stock with a valuation of $390,000 that was issued to an investor relations firm in the first quarter of 2017. Going Concern As of March 31, 2017, there is substantial doubt regarding our ability to continue as a going concern as we have not generated sufficient cash flow to fund our proposed business. We have suffered recurring losses from operations since our inception. In addition, we have yet to generate an internal cash flow from our business operations or successfully raised the financing required to develop our proposed business. As a result of these and other factors, our independent auditor has expressed substantial doubt about our ability to continue as a going concern. Liquidity and Capital Resources We had no cash as of the date of March 31, 2017. Additionally, since there is no balance sheet in the last 10-Q (another bad sign), the last annual report 10-K has this balance sheet: So the company: So why did the stock value plummet? It's anyones' guess but there is no shortage of ways to justify it. In fact, it's reasonable to ask how is this company still worth $3mm ($1 * 3mm shares outstanding)...","title":""},{"docid":"151871","text":"\"Their is no arbitrage opportunity with \"\"buying dividends.\"\" You're buying a taxable event. This is a largely misunderstood topic. The stock always drops by the amount if the dividend on the ex date. The stock opens that day trading \"\"ex\"\" (excluding) the dividend. It then pays out later based in the shareholders on record. There is a lot of talk about price movement and value here. That can happen but it's from trading not from the dividend per se. Yes sometimes you do see a stock pop the day prior to ex date because people are buying the stock for the dividend but the trading aspect of a stock is determined by supply and demand from people trading the stock. The dividends are paid out from the owners equity section of the balance sheet. This is a return of equity to shareholders. The idea is to give owners of the company some of their investment back (from when they bought the stock) without having the owners sell the shares of the company. After all if it's a good company you want to keep holding it so it will appreciate. Another similar way to think of it is like a bonds interest payment. People sometimes forget when trading that these are actual companies meant to be invested in. Your buying an ownership in the company with your cash. It really makes no difference to buy the dividend or not, all other things constant. Though market activity can add or lose value from trading as normal.\"","title":""},{"docid":"506460","text":"First, I want to point out that your question contains an assumption. Does anyone make significant money trading low volume stocks? I'm not sure this is the case - I've never heard of a hedge fund trading in the pink sheets, for example. Second, if your assumption is valid, here are a few ideas how it might work: Accumulate slowly, exit slowly. This won't work for short-term swings, but if you feel like a low-volume stock will be a longer-term winner, you can accumulate a sizable portion in small enough chunks not to swing the price (and then slowly unwind your position when the price has increased sufficiently). Create additional buyers/sellers. Your frustration may be one of the reasons low-volume stock is so full of scammers pumping and dumping (read any investing message board to see examples of this). If you can scare holders of the stock into selling, you can buy significant portions without driving the stock price up. Similarly, if you can convince people to buy the stock, you can unload without destroying the price. This is (of course) morally and legally dubious, so I would not recommend this practice.","title":""},{"docid":"160421","text":"When I read that part of his post, it reminded me more of credit companies rather than banks. People default on credit all the time. I have no idea what the regulations are on the amount of credit that a company can issue, though. And this is sort of part of what actually happened in the beginning of the economic crunch. A bunch of people began to trade for credit (debt) against what they thought the *future* value of their house or other real estate would be. After a while, people stopped being able to afford property at its future value, so they stopped buying it. When people then tried to sell their property for the future value that they had borrowed against, they couldn't, so they couldn't pay back their debt. Because real estate had become a popular investment vehicle for the middle class, this was able to reach a kind of critical mass, and shortly afterward the effects rippled back into the credit market, which also had its own crunch -- a bunch of credit just disappeared overnight because so many people had assumed a level of debt that they could not actually fulfill their promises on once the future value of their home became completely imaginary.","title":""},{"docid":"365465","text":"\"Very simple. You open an account with a broker who will do the trades for you. Then you give the broker orders to buy and sell (and the money to pay for the purchases). That's it. In the old days, you would call on the phone (remember, in all the movies, \"\"Sell, sell!!!!\"\"? That's how), now every decent broker has an online trading platform. If you don't want to have \"\"additional value\"\" and just trade - there are many online discount brokers (ETrade, ScotTrade, TD Ameritrade, and others) who offer pretty cheap trades and provide decent services and access to information. For more fees, you can also get advices and professional management where an investment manager will make the decisions for you (if you have several millions to invest, that is). After you open an account and login, you'll find a big green (usually) button which says \"\"BUY\"\". Stocks are traded on exchanges. For example the NYSE and the NASDAQ are the most common US exchanges (there's another one called \"\"pink sheets\"\", but its a different kind of animal), there are also stock exchanges in Europe (notably London, Frankfurt, Paris, Moscow) and Asia (notably Hong Kong, Shanghai, Tokyo). Many trading platforms (ETrade, that I use, for example) allow investing on some of those as well.\"","title":""},{"docid":"593644","text":"NSCC illiquid charges are charges that apply to the trading of low-priced over-the counter (OTC) securities with low volumes. Open net buy quantity represents the total unsettled share amount per stock at any given time during a 3-day settlement cycle. Open net buy quantity must be less than 5,000,000 shares per stock for your entire firm Basically, you can't hold a long position of more than 5 million shares in an illiquid OTC stock without facing a fee. You'll still be assessed this fee if you accumulate a long position of this size by breaking your purchase up into multiple transactions. Open net sell quantity represents the total unsettled share amount per stock at any given time during a 3-day settlement cycle. Open net sell quantity must be less than 10% percent of the 20-day average volume If you attempt to sell a number of shares greater than 10% of the stock's average volume over the last 20 days, you'll also be assessed a fee. The first link I included above is just an example, but it makes the important point: you may still be assessed a fee for trading OTC stocks even if your account doesn't meet the criteria because these restrictions are applied at the level of the clearing firm, not the individual client. This means that if other investors with your broker, or even at another broker that happens to use the same clearing firm, purchase more than 5 million shares in an individual OTC stock at the same time, all of your accounts may face fees, even though individually, you don't exceed the limits. Technically, these fees are assessed to the clearing firm, not the individual investor, but usually the clearing firm will pass the fees along to the broker (and possibly add other charges as well), and the broker will charge a fee to the individual account(s) that triggered the restriction. Also, remember that when buying OTC/pink sheet stocks, your ability to buy or sell is also contingent on finding someone else to buy from/sell to. If you purchase 10,000 shares one day and attempt to sell them sometime in the future, but there aren't enough buyers to buy all 10,000 from you, you might not be able to complete your order at the desired price, or even at all.","title":""},{"docid":"61418","text":"\">BPI took such a hard hit because they showed the world that they're the type of company willing to sell people really nasty shit just to make a buck (in my opinion). Honestly, if there was a news expose on 90% of the processed food that is on grocery store shelves, people would have the same reaction. You would be shocked as to what happens in food manufacturing facilities. Yes, there are FDA, USDA, and many other agencies that do both announced and surprise audits of food manufacturers to ensure food safety, but this is just a snapshot in time, and the food is only deemed as safe as to the standards of that company and what the definition of \"\"safe\"\" is. IMO, yes, BPI took a huge hit because of this being called pink slime. Are they manufacturing something that is potentially dangerous for consumption? Possibly. That all depends on who you ask what \"\"safe for consumption\"\" means. Are lobbyists involved? Bet your ass they are. But the market at the time was demanding a type of beef that was super lean. All BPI did was find a way to fulfill that need. I don't know what the outcome of this will be, but I can absolutely see both sides of the argument. The press needs to be free to report on anything and everything. However, there needs to be regulation regarding what they can and can not say from a slander standpoint. Coming up with a cute catch phrase such as \"\"pink slime\"\" is slanderous, and potentially damaging. That's where I agree with you and believe that they should have reported on the factual inclusions in the finished product. /rant\"","title":""},{"docid":"393925","text":"Many of the major indices retreated today because of this news. Why? How do the rising budget deficits and debt relate to the stock markets? It does seem strange that there is a correlation between government debt and the stock market. But I could see many reasons for the reaction. The downgrade by S&P may make it more expensive for the government to borrow money (i.e. higher interest rates). This means it becomes more expensive for the government to borrow money and the government will probably need to raise taxes to cover the cost of borrowing. Rising taxes are not good for business. Also, many banks in the US hold US government debt. Rising yields will push down the value of their holdings which in turn will reduce the value of US debt on the businesses' balance sheets. This weakens the banks' balance sheets. They may even start to unload US bonds. Why is there such a large emphasis on the S&P rating? I don't know. I think they have proven they are practically useless. That's just my opinion. Many, though, still think they are a credible ratings agency. What happens when the debt ceiling is reached? Theoretically the government has to stop borrowing money once the debt ceiling is reached. If this occurs and the government does not raise the debt ceiling then the government faces three choices:","title":""},{"docid":"542765","text":"Using Fundamental and Technical Analysis together is actually a good idea for longer term trading of up to 6 months or longer. The whole idea behind trading with Technical Analysis is to increase the probabilities of a trade going in the desired direction by using uncorrelated indicators that produce the same signal to buy or sell at the same time. For example, you might use a Moving Average (MA) as a buy signal when the price falls for a few days, hits the MA and then reverses and starts moving back up. If however, you also include a Stochastic Oscillator (SO) to indicate when the stock is oversold (under 20%), and if the price rebounds from the MA average at the same time as the Stochastic is crossing over in the oversold position, then this may be a higher probability trade. If you also only trade stocks that are Fundamentally healthy (as fundamentally good stocks are more likely to go up than fundamentally bad stocks) then this might increase the probabilities again. Then if you only buy when the market as a whole is moving up, then this will increase your chances again. A few weeks ago at a seminar, the presenter totalled the men in the room to be 76 and the women in the room to be 8. He then asked what will most likely be the next person to walk in the room - a man or a woman? The statistics are on the side of a wan walking in next. This is what we try to do with Technical Analysis, increase our chances when we take a trade. Of course a woman could be the next person to walk in the room, just like any trade can go against you, and this is why we use money management and risk management and take a small loss when a trade does go against you. Lets look at an example where you could incorporate FA with TA to increase your chances of profits: Above is a candlestick chart of Select Harvest (SHV), the green line above the price is the perceived value, the pink line is the 40 day MA, the blue line is the EPS, and the white lines is the Stochastic Oscillator (above 80% being overbought and below 20% is oversold). From Feb 2015 to start of Aug 2015 the stock was uptrending, since then the price reversed and started to downtrend. The stock was determined to be fundamentally good early in 2015 with the perceived value gradually increasing and greater than the share price, and the EPS starting to increase regularly from mid April. Thus, as the stock is seen as fundamentally healthy any price reversal in the vicinity of the MA could be seen as a buy opportunity. In fact there where 2 such opportunities on 31st March and 11th June where price had reversed and rebounded off the MA whist the SO crossed over in or near the oversold area. The price did reverse and then rebounded off the MA again on 9th July, however the SO was not in or near the oversold area on this occasion, so not as high in probability terms. The price still rebounded and went up again, however another momentum indicator (not shown here) shows some bearish divergence in this case - so another reason to possibly keep away at this point in time. A good signal to get out of the trade, that is your stop loss has not already taken you out, is when the price breaks and closes below the MA line. This occurred on 7th August. So if we had bought on the first signal on 31st March for $7.41 and sold when the priced broke through the MA on 7th August for $11.76, we would have made a profit of approx. 59% in just over 4 months. If bought on the second signal on 11th June for $9.98 and again sold on 7th August for $11.76, we would have made about 18% in under 2 months. So the fundamentals, the Price (in relation to MA) and the SO where all lining up to provide two high probability trades. Of course you would need to incorporate you risk management (including stops) in case the price did not continue upwards after you bought. If the market is also moving up on the day of the signal this will further increase your chances. Unless you day trade, which I would avoid, a good way to enter your trades after a signal is to enter a stop buy order after market close to buy if the price moves above the high of the signal day. That way if the market and the stock open and move lower during the day after the signal you avoid entering the trade altogether. This can be incorporated as part of your risk management and trading rules. After the price broke down through the MA we can see that a downtrend commenced which is still current today (in fact I just took a short trade on this stock yesterday). We can also see that the perceived value, whilst still above the price, has reached a peak and is currently moving downwards and the EPS after being flat for a few months has just moved down for the first time in 10 months. So maybe the fundamentals are starting to waver a bit on this stock. It may be a good stock to continue shorting into the future. So basically you can continue using Fundamental Analysis to select which stocks to buy, place them in a watch-list, and then use Technical Analysis to determine when these stocks are starting to uptrend and use a combination of uncorrelated indicators to produce higher probability signals for when to enter your trades.","title":""},{"docid":"565971","text":">PI’s attorney, Dan Webb, said in court Monday that ABC used the term “pink slime” 350 times over the course of its reporting, and that ABC willfully spread this preconceived, negative message. Webb also showed the jurors a picture of lean finely textured beef. “It physically doesn’t look like slime,” he said. It physically doesn't look like slime, and presumably it isn't slime chemically. What's their reason for calling it 'pink slime'? >In fact, the term “pink slime” was coined by one of the segment’s whistleblowing USDA scientists in a 2002 email to colleagues, and a 2009 New York Times piece using the term to describe BPI’s meat product won a Pulitzer Prize. So, they coined a word to describe something that was intentionally designed to sensationalize it, in a negative way. If I were on the jury this is the point of fact that I'd base my vote on. The media needs to be slapped pretty hard when they start actively damaging people and companies to sell stories.","title":""},{"docid":"287325","text":"\"What could the tax issues with the IRS be? I thought (but not totally certain) that the tax treatment of an ISO option was based on difference between exercise price and FMV at the time of the sale. This is an accounting issue. There were times not so long ago that companies actually did these things on purpose, to boost the stock grant values for their employees (especially senior employees). They would give a grant but date it with an earlier date with a more favorable valuation. This is called \"\"backdating\"\", and it brought companies down and CEOs into criminal courts. In addition, only reasonable compensation is allowed as a deduction for the company, and incorrectly set strike price may be deemed unreasonable. Thus, the deduction the company would take for your compensation can be denied, leading to loss of tax benefit (this was also a weapon used by the IRS at the time against companies doing backdating). Last but not least, company that has intentions of going public cannot allow itself such a blatant disregard of the accounting rules. Even if the mistake was not made on purpose (as it sounds), it is a mistake that has to be corrected. What should I take into consideration to determine whether a 27% increase in shares is a fair exchange for an increase in 270% increase in strike price. Did you know the strike price when you signed the contract? Was it a consideration for you? For most people, the strike price is determined at the board approval, since the valuations are not public and are not disclosed before you actually join, which is already after you've agreed to the terms. So basically, you agreed to get 100 sheets of toilet paper, and instead getting 127 sheets. So you're getting 27 sheets more than you initially agreed to. Why are you complaining? In other words, options are essentially random numbers which are quite useless. By the time you get to exercise them, they'll be diluted through a bunch of additional financing rounds, and their value will be determined for real only after the IPO, or at least when your company's stocks are trading OTC with some reasonable volume. Until then - it's just a number with not much of a meaning. The FMV does matter for early exercise and 83(b) election, if that is an option, but even then - I doubt you can actually negotiate anything.\"","title":""},{"docid":"316673","text":"We constantly hear that there are not enough trades-people to fill manufacturing roles. This is what happens when you offshore everything possible for the last 30 years. No one wants to go into a trade that will be offshored plus there are too few of those positions to apprentice in. Stop the boo-hooing big business, man-up and invest in some of your fellow citizens.","title":""},{"docid":"312811","text":"\"Share sales & purchases are accounted only on the balance sheet & cash flow statement although their effects are seen on the income statement. Remember, the balance sheet is like a snapshot in time of all accrued accounts; it's like looking at a glass of water and noting the level. The cash flow and income statements are like looking at the amount of water, \"\"actually\"\" and \"\"imaginary\"\" respectively, pumped in and out of the glass. So, when a corporation starts, it sells shares to whomever. The amount of cash received is accounted for in the investing section of the cash flow statement under the subheading \"\"issuance (retirement) of stock\"\" or the like, so when shares are sold, it is \"\"issuance\"\"; when a company buys back their shares, it's called \"\"retirement\"\", as cash inflows and outflows respectively. If you had a balance sheet before the shares were sold, you'd see under the \"\"equity\"\" heading a subheading common stock with a nominal (irrelevant) par value (this is usually something obnoxiously low like $0.01 per share used for ease of counting the shares from the Dollar amount in the account) under the subaccount almost always called \"\"common stock\"\". If you looked at the balance sheet after the sale, you'd see the number of shares in a note to the side. When shares trade publicly, the corporation usually has very little to do with it unless if they are selling or buying new shares under whatever label such as IPO, secondary offering, share repurchase, etc, but the corporation's volume from such activity would still be far below the activity of the third parties: shares are trading almost exclusively between third parties. These share sales and purchases will only be seen on the income statement under earnings per share (EPS), as EPS will rise and fall with stock repurchases and sales assuming income is held constant. While not technically part of the income statement but printed with it, the \"\"basic weighted average\"\" and \"\"diluted weighted average\"\" number of shares are also printed which are the weighted average over the reporting period of shares actually issued and expected if all promises to issue shares with employee stock options, grants, convertibles were made kept. The income statement is the accrual accounts of the operations of the company. It has little detail on investing (depreciation & appreciation) or financing (interest expenses & preferred dividends).\"","title":""},{"docid":"407274","text":"There are lots of good points here already, but something that hasn't been mentioned yet is what would happen if the purchased items break or are somehow defective? Depending on the warranty and how trustworthy the company is, there could be an advantage to not having fully paid for the item yet when a defect is discovered, as it might incentivize the company to be more attentive to your warranty claim, since they are faced with knowing that you could stop making payments if they don't act in a timely manner. Note I'm not suggesting you stop making payments in this case, just that companies (and banks) are oftentimes more willing to work with you when you owe them money.","title":""},{"docid":"301547","text":"\"To my knowledge, there's no universal equation, so this could vary by individual/company. The equation I use (outside of sentiment measurement) is the below - which carries its own risks: This equations assumes two key points: Anything over 1.2 is considered oversold if those two conditions apply. The reason for the bear market is that that's the time stocks generally go on \"\"sale\"\" and if a company has a solid balance sheet, even in a downturn, while their profit may decrease some, a value over 1.2 could indicate the company is oversold. An example of this is Warren Buffett's investment in Wells Fargo in 2009 (around March) when WFC hit approximately 7-9 a share. Although the banking world was experiencing a crisis, Buffett saw that WFC still had a solid balance sheet, even with a decrease in profit. The missing logic with many investors was a decrease in profits - if you look at the per capita income figures, Americans lost some income, but not near enough to justify the stock falling 50%+ from its high when evaluating its business and balance sheet. The market quickly caught this too - within two months, WFC was almost at $30 a share. As an interesting side note on this, WFC now pays $1.20 dividend a year. A person who bought it at $7 a share is receiving a yield of 17%+ on their $7 a share investment. Still, this equation is not without its risks. A company may have a solid balance sheet, but end up borrowing more money while losing a ton of profit, which the investor finds out about ad-hoc (seen this happen several times). Suddenly, what \"\"appeared\"\" to be a good sale, turns into a person buying a penny with a dollar. This is why, to my knowledge, no universal equation applies, as if one did exist, every hedge fund, mutual fund, etc would be using it. One final note: with robotraders becoming more common, I'm not sure we'll see this type of opportunity again. 2009 offered some great deals, but a robotrader could easily be built with the above equation (or a similar one), meaning that as soon as we had that type of environment, all stocks fitting that scenario would be bought, pushing up their PEs. Some companies might be willing to take an \"\"all risk\"\" if they assess that this equation works for more than n% of companies (especially if that n% returns an m% that outweighs the loss). The only advantage that a small investor might have is that these large companies with robotraders are over-leveraged in bad investments and with a decline, they can't make the good investments until its too late. Remember, the equation ultimately assumes a person/company has free cash to use it (this was also a problem for many large investment firms in 2009 - they were over-leveraged in bad debt).\"","title":""}],"string":"[\n {\n \"docid\": \"278889\",\n \"text\": \"\\\"Changing my answer based on clarification in comments. It appears that some of the securities you mentioned, including GEAPP, are traded on what is colloquially known as the Grey Market. Grey Sheets, and also known as the \\\"\\\"Gray Market\\\"\\\" is another category of OTC stocks that is completely separate from Pink Sheets and the OTCBB. From investopedia The grey market is an over-the-counter market where dealers may execute orders for preferred customers as well as provide support for a new issue before it is actually issued. This activity allows underwriters and the issuer to determine demand and price the securities accordingly before the IPO. Some additional information on this type of stocks. (Source) Unlike other financial markets... No recent bid or ask quotes are available because no market makers share data or quote such stocks. There is no quoting system available to record and settle trades. All Grey sheet trading is moderated by a broker and done between consenting individuals at a price they agree on. The only documentation that can be publicly found regarding the trades is when the last trade took place. No SEC registration and little SEC regulation. Regulation of Grey Sheet stocks takes place mainly on a state level. Unlike Pink Sheets, these stocks have no SEC registration to possess a stock symbol or to possess shares or trade shares of that stock. Such penny stocks, similar to Pink Sheets, are not required to file SEC (Securities and Exchange Commission) financial and business reports. These stocks may not be solicited or advertised to the public unless a certain number of shares are qualified to be traded publicly under 504 of Regulation D. Extremely Illiquid. Gray sheet trading is infrequent, and for good reason... Difficult to trade, not advertised, difficult to follow the price, the least regulation possible, hard to find any information on the stock, very small market cap, little history, and most such stocks do not yet offer public shares. The lack of information (bids, history, financial reports) alone causes most investors to be very skeptical of Gray Sheets and avoid them altogether. Gray Sheets are commonly associated with Initial public offering (IPO) stocks or start up companies or spin-off companies, even though not all are IPO's, start-ups or spin-offs. Grey Sheets is also Home to delisted stocks from other markets. Some stocks on this financial market were once traded on the NASDAQ, OTCBB, or the Pink Sheets but ran into serious misfortune - usually financial - and thus failed to meet the minimum requirements of the registered SEC filings and/or stock exchange regulations for a financial market. Such stocks were delisted or removed and may begin trading on the Grey Sheets. So to answer your question, I think the cause of the wild swings is that: Great question, BTW.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"107227\",\n \"text\": \"popularity that you are referring to is just known as liquidity when discussing markets. More liquid securities tend to trade more shares per day and have very tight bid/ask spreads as many investors are buying and selling the shares at one time. Some larger securities, especially on exchanges, further enhance liquidity by providing market makers. These are individuals on the NYSE, for example, that will make the market in large securities by handling large orders and providing liquidity through their own book of capital. The individuals on the floor on the NYSE you often see on TV are those market makers. However, as trading becomes more electronic, market markers are becoming less and less required. A previous comment suggested pink sheets are risky companies. This is not entirely factual. While the majority of pink sheets are very highly risky companies, many very solid international companies trade their ADRs (American Depository Receipt) on the pink sheets to avoid the high cost of setting up a large exchange at the NYSE and register and report through the SEC. As a TD Ameritrade user, I would be willing to help you out if you have any other questions.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"261640\",\n \"text\": \"\\\"The penny/pink sheet stocks you tend to see promoted are the ones a) with small public floats or, b) they are thinly traded. This means that any appreciable change in buy/sell volume will have an outsized effect on the stock's share price, even when the underlying fundamentals are not so great. Promoters are frequently paid based on how much they can move a stock's price, but such moves are not long-lasting. They peter out when the trading volumes return to more normal ranges for the stock because all of the hype has died out. There are some small-cap NASDAQ stocks which can be susceptible to promotion for the same reason -- they have small floats and/or are thinly traded. Once someone figures out the best targets, they'll accumulate a position and then start posting all kinds of \\\"\\\"news\\\"\\\" on the web in an effort to drum up interest so they can sell off their position into the buying that follows. The biggest problem with penny/pink sheet stocks is that they frequently fail to publish reliable financial statements, and their ownership is of a dubious nature. In the past, these types of stocks have been targeted by organized crime syndicates, which ran their own \\\"\\\"pump and dump\\\"\\\" operations as a way to make relatively easy money. This may still be true to some extent today. Be wary of investing in any publicly-traded firm that has to use promoters to drum up investor interest, because it can be a serious red flag. Even if it means missing out on a short-term opportunity, research the company before investing. Read its financials, understand how it has behaved through its trading history, learn about the products/services it is selling. Do your homework. Otherwise you are doing the investing equivalent of taking your money and lighting it on fire. Remember, there's a good reason these companies are trading as penny/pink sheet stocks, and it generally has nothing to do with the notion (the promoters will tell you) that somehow the \\\"\\\"market has missed out on this amazing opportunity.\\\"\\\" Pump and dump schemes, which lie at the heart of almost all stock promotion, rely on convincing you, the investor, that you're smart enough to see what others haven't. I hope this helps. Good luck!\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"510163\",\n \"text\": \"\\\"The Minnesota Mining and Manufacturing Company was established in 1902 as a private company. It first raised public funds around 1903 but had a limited shareholder base. By around 1929, it was reported as being tradeable as an OTC (over-the-counter) stock but it's likely that shares were traded well before this. On 14 Jan 1946, the stock was listed on NYSE. On 26 Sep 1962 it became a constituent of the the S&P 500 index. On 9 Aug 1976 it became a constituent of the Dow Jones Industrial Average. In 2002, the company's name changed to 3M Co. It appears that the data on Crunchbase's \\\"\\\"IPO Date\\\"\\\" is wrong on this one. However, there are several companies that appear to do an \\\"\\\"IPO\\\"\\\" and have trading prices prior. This is quite typical of early-stage biotech companies that trade OTC prior to a major exchange listing and \\\"\\\"IPO\\\"\\\". An example of an IPO happening after a company became publicly tradeable is NASDAQ:IMRN (Immuron). They had an \\\"\\\"IPO\\\"\\\" on Nasdaq on 9 Jun 2017, yet they had been trading as an OTC/Pink Sheet stock for months prior. They also have been listed in Australia since 30 Apr 1999. http://www.nasdaq.com/markets/ipos/activity.aspx?tab=pricings&month=2017-06 Another example is NASDAQ:GNTY (Guaranty Banchshares Inc) which had an \\\"\\\"IPO\\\"\\\" and NASDAQ listing in May 2017. This was a Nasdaq stock in 1998, went OTC/pink sheet stock in 2005. It has been paying regular dividends since that time. Clearly the word \\\"\\\"Initial\\\"\\\" is subjective! http://www.nasdaq.com/markets/ipos/activity.aspx?tab=pricings&month=2017-05\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"165973\",\n \"text\": \"It depends on what site you're looking on and what exchange they're pulling the data from. Even though funds and stocks are called the same thing, they have different ticker symbols in each country's exchange or could be traded as pink sheet stocks in the US. If a company or fund is based in another country (like Canada or the UK) they probably also trade on that country's exchange (Toronto or London) under a different symbol. This can cause a lot of confusion when researching these tickers.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"253847\",\n \"text\": \"While most all Canadian brokers allow us access to all the US stocks, the reverse is not true. But some US brokers DO allow trading on foreign exchanges. (e.g. Interactive Brokers at which I have an account). You have to look and be prepared to switch brokers. Americans cannot use Canadian brokers (and vice versa). Trading of shares happens where-ever two people get together - hence the pink sheets. These work well for Americans who want to buy-sell foreign stocks using USD without the hassle of FX conversions. You get the same economic exposure as if the actual stock were bought. But the exchanges are barely policed, and liquidity can dry up, and FX moves are not necessarily arbitraged away by 'the market'. You don't have the same safety as ADRs because there is no bank holding any stash of 'actual' stocks to backstop those traded on the pink sheets.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"291903\",\n \"text\": \"\\\"Pink Sheets is not a stock exchange per se, and securities traded through it are not as \\\"\\\"safe\\\"\\\" as the ones on a stock exchange regulated by SEC. Many companies are traded there because they failed to comply with the SEC regulations, or are bankrupt or don't want the level of reporting to the public that the SEC regulations require. Since you're talking about an ADR of a company traded on LSE, it might be much safer that other, \\\"\\\"regular\\\"\\\", securities, but still it means that you're buying an unregulated security (even if it is of a company regulated elsewhere). Notice the volume of trades: mere thousands of dollars per day (in a good day, in some days there are no trades at all). It makes it harder to sell the security when needed. Why not buying at LSE?\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"54257\",\n \"text\": \"\\\"If you own 1% of a company, you are technically entitled to 1% of the current value and future profits of that company. However, you cannot, as you seem to imply, just decide at some point to take your ball and go home. You cannot call up the company and ask for 1% of their assets to be liquidated and given to you in cash. What the 1% stake in the company actually entitles you to is: 1% of total shareholder voting rights. Your \\\"\\\"aye\\\"\\\" or \\\"\\\"nay\\\"\\\" carries the weight of 1% of the total shareholder voting block. Doesn't sound like much, but when the average little guy has on the order of ten-millionths of a percentage point ownership of any big corporation, your one vote carries more weight than those of millions of single-share investors. 1% of future dividend payments made to shareholders. For every dollar the corporation makes in profits, and doesn't retain for future growth, you get a penny. Again, doesn't sound like much, but consider that the Simon property group, ranked #497 on the Fortune 500 list of the world's biggest companies by revenue, made $1.4 billion in profits last year. 1% of that, if the company divvied it all up, is $14 million. If you bought your 1% stake in March of 2009, you would have paid a paltry $83 million, and be earning roughly 16% on your initial investment annually just in dividends (to say nothing of the roughly 450% increase in stock price since that time, making the value of your holdings roughly $460 million; that does reduce your actual dividend yield to about 3% of holdings value). If this doesn't sound appealing, and you want out, you would sell your 1% stake. The price you would get for this total stake may or may not be 1% of the company's book value. This is for many reasons: Now, to answer your hypothetical: If Apple's stock, tomorrow, went from $420b market cap to zero, that would mean that the market unanimously thought, when they woke up tomorrow morning, that the company was all of a sudden absolutely worthless. In order to have this unanimous consent, the market must be thoroughly convinced, by looking at SEC filings of assets, liabilities and profits, listening to executive statements, etc that an investor wouldn't see even one penny returned of any cash investment made in this company's stock. That's impossible; the price of a share is based on what someone will pay to have it (or accept to be rid of it). Nobody ever just gives stock away for free on the trading floor, so even if they're selling 10 shares for a penny, they're selling it, and so the stock has a value ($0.001/share). We can say, however, that a fall to \\\"\\\"effectively zero\\\"\\\" is possible, because they've happened. Enron, for instance, lost half its share value in just one week in mid-October as the scope of the accounting scandal started becoming evident. That was just the steepest part of an 18-month fall from $90/share in August '00, to just $0.12/share as of its bankruptcy filing in Dec '01; a 99.87% loss of value. Now, this is an extreme example, but it illustrates what would be necessary to get a stock to go all the way to zero (if indeed it ever really could). Enron's stock wasn't delisted until a month and a half after Enron's bankruptcy filing, it was done based on NYSE listing rules (the stock had been trading at less than a dollar for 30 days), and was still traded \\\"\\\"over the counter\\\"\\\" on the Pink Sheets after that point. Enron didn't divest all its assets until 2006, and the company still exists (though its mission is now to sue other companies that had a hand in the fraud, get the money and turn it around to Enron creditors). I don't know when it stopped becoming a publicly-traded company (if indeed it ever did), but as I said, there is always someone willing to buy a bunch of really cheap shares to try and game the market (buying shares reduces the number available for sale, reducing supply, increasing price, making the investor a lot of money assuming he can offload them quickly enough).\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"454465\",\n \"text\": \"If you are trying to invest in closely held / private companies (things that don't trade on the stock market), you will run into a variety of regulatory problems. For various reasons, most private companies only raise funds with accredited investors. To be an accredited investor you basically have to have $1,000,000 in net worth - NOT including your primary residence, OR you have to make over $200,000 a year for the last two years and expect to keep making that much. This is a class distinction the Federal government created, you will see different but similar wealth and investment classes worldwide. So your best most organized opportunities are left out, unless you do qualify as an accredited investor. There are tons of other companies, things you will find locally, that will let you invest in their smaller time operations. (Think like a local yoga studio looking for $20,000 and willing to split the profits with you). But the problem here is lack of accountability, where partners skip town or just stop answering your calls, and the legal remedies cost you more than your claim. That being said there are people that provide capital to smaller publicly traded companies on the bulletin boards and pink sheets. They have opportunities do much better than the actual stock market investors in these companies, because you can negotiate contracts that let you cash out in their inevitable financing death spirals with very little risk to you. You can do these things as an individual or as a holding company, but the holding company will limit your liability to the amount your holding company invested, instead of your personal assets, in case your financing starts to incur liability with the company.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"404936\",\n \"text\": \"Depends on the structure of the company and what shares are outstanding. If the pink sheet stock has no voting power then buying all that stock doesn't get you any control at all. On the other hand, if the outstanding shares only represent 20% of the company's overall shares, then buying all the shares isn't likely enough to have a controlling interest. Thus, you'll have to dig into the details. If you want an example of where I'd have my doubts, look at Nestle's stock which has the ticker of NSRGY. There can be companies that are structured with stock on multiple exchanges that can also be a challenge at times. There is also something to be said if you own enough stock in a company that this has to be disclosed to the SEC when you buy more.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"319599\",\n \"text\": \"Well I'm not going to advise whether it's a good idea to invest in this company (though often OTC is pretty scary), but it DOES have a product (vivio, an ad blocker), it did post financials and it's trading on the OTC-QB (which is better than the pink sheets), so you need to look these over and study up on the product to decide if it is overpriced or not. What might have occurred (viz the Patriot Berry Farm becoming Cyberfort) is that the latter bought up the stock of the former (this is, I believe, called using a shell, which is not necessarily a bad thing) and is using this as a way to be registered, i.e. sell to non-accredited investors via the OTC market. So I'm really just answering your third question: yes, you have to do a lot of due diligence to see if buying this stock is a good deal or not. It might be the next big thing. Or it might not. It certainly is the case that low trading volume allows a relatively small trade to really change the stock price, so the penny stocks do tend to be easier to 'inflate'. Side comment: the bid/ask spreads are pretty big, with a best bid of 0.35 and best ask of 0.44.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"110584\",\n \"text\": \"For the lazy, Wikipedia says: The term microcap stock (also micro-cap) refers to the stock of public companies in the United States which have a market capitalization of roughly $300 million or less. The shares of companies with a market capitalization of less than $50 million are typically referred to as nano-cap stocks. Many micro-cap and nano-cap stocks are traded over-the-counter with their prices quoted on the OTCBB or the Pink Sheets. A few of the larger, more established microcaps are listed on the NASDAQ Capital Market or American Stock Exchange (AMEX). Micro-cap and especially nano-cap stocks are notorious for their volatility. A high percentage of these companies fail to execute their business plans and go out of business. Fraud and market manipulation are not uncommon, and the transactions costs in trading can be quite high. Pricing is more likely to be inefficient, since fewer institutional investors and analysts operate in this space, due to the relatively small dollar amounts involved and the lack of liquidity.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"495255\",\n \"text\": \"I'd call it pretty worrisome. HOOB is trading over the counter, in fact, on the pink sheets, so it has been delisted from the major exchanges. It appears that it lacks recent financial disclosures. You'll have to investigate to see if you think it's worth keeping, but trading is thin.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"555047\",\n \"text\": \"I traded futures for a brief period in school using the BrokersXpress platform (now part of OptionsXpress, which is in turn now part of Charles Schwab). They had a virtual trading platform, and apparently still do, and it was excellent. Since my main account was enabled for futures, this carried over to the virtual account, so I could trade a whole range of futures, options, stocks, etc. I spoke with OptionsXpress, and you don't need to fund your acount to use the virtual trading platform. However, they will cancel your account after an arbitrary period of time if you don't log in every few days. According to their customer service, there is no inactivity fee on your main account if you don't fund it and make no trades. I also used Stock-Trak for a class and despite finding the occasional bug or website performance issue, it provided a good experience. I received a discount because I used it through an educational institution, and customer service was quite good (probably for the same reason), but I don't know if those same benefits would apply to an individual signing up for it. I signed up for top10traders about seven years ago when I was in secondary school, and it's completely free. Unfortunately, you get what you pay for, and the interface was poorly designed and slow. Furthermore, at that time, there were no restrictions that limited the number of shares you could buy to the number of outstanding shares, so you could buy as many as you could afford, even if you exceeded the number that physically existed. While this isn't an issue for large companies, it meant you could earn a killing trading highly illiquid pink sheet stocks because you could purchase billions of shares of companies with only a few thousand shares actually outstanding. I don't know if these issues have been corrected or not, but at the time, I and several other users took advantage of these oversights to rack up hundreds of trillions of dollars in a matter of days, so if you want a realistic simulation, this isn't it. Investopedia also has a stock simulator that I've heard positive things about, although I haven't used it personally.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"390779\",\n \"text\": \"\\\"The assumption that companies listed OTC are not serious is far from the truth. Many companies on the OTC are just starting off there because they don't meet the requirements to be listed on the NASDAQ or NYSE. Major stock exchanges like the NASDAQ and the NYSE only want the best companies to trade on their exchanges.The NASDAQ, for example, has three sets of listing requirements. A company must meet at least one of the three requirement sets, as well as the main rules for all companies. These include: Now don't assume that the OTC doesn't have rules either, as this is far from the truth as well. While there are no minimum level of revenue, profits or assets required to get listed on the OTC there are requirements for audited financial statements and ongoing filing and reporting to the SEC and NASD. Additionally there are several different levels of the OTC, including the OTCQX, the OTCCB and the OTC Pink, each with their own set of requirements. For more information about what it takes to be listed on OTC look here: http://www.otcmarkets.com/learn/otc-trading A company deciding to trade on the OTC is making the decision to take their company public, and they are investing to make it happen. Currently the fees to get listed on the OTC range from $30,000 to $150,000 depending on the firm you decide to go with and the services they offer as part as their package. Now, I know I wouldn't consider $30K (or more) to not be serious money! When I looked into the process of getting a company listed on the TSX the requirements seemed a lot more relaxed than those of the major U.S. markets as well, consisting of an application, records submission and then a decision made by a TSX committee about whether you get listed. More information about the TSX here: http://apps.tmx.com/en/listings/listing_with_us/process/index.html I think the way that the OTC markets have gotten such a bad reputation is from these \\\"\\\"Get Rich on Penny Stock\\\"\\\" companies that you see pumping up OTC company stocks and getting massive amounts of people to buy without doing their due diligence and investigating the company and reading its prospectus. Then when they loose a bunch of money on an ill-informed investment decision they blame it on the company being an OTC stock. Whether you decide to trade the OTC market or not, I wouldn't make a decision based on how many exchanges the company is listed on, but rather based on the research you do into the company.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"129481\",\n \"text\": \"I'm going to guess that you found this because of a stock screener. This company went through a 1:20 reverse split on June 30, so every 20 shares outstanding became a single share. Where before you had 20 shares worth $100 you now have 1 share worth $100, the value of the company doesn't change because of a split. This company was never trading for $30+ per share. Reverse splits are typical of a floundering company trading on an exchange that has a minimum share price requirement. While reverse splits don't change the value of the company, just the number of shares outstanding and the price per share, no healthy company performs a reverse split. Reverse splits are generally a massive signal to jump ship... The company seems to be trading for $1 right now, why the value fell from a pre-split $1.65 ($33/20) to $1 is anyone's guess; how the company ever got to $1.65 is also anyone's guess. But looking at the most recent 10-Q there are numerous causes for concern: Note 2. Capital Stock On March 6, 2017, the Company issued as compensation for services provided a total of 650,000 common shares with a fair value of $390,000 to a third party. The fair value of the shares was based on the price quoted on the OTC pink sheets on the grant date. this indicates a share price of $0.60 ($390,000/650,000) as of 3/6/2017, just to reinforce that the google price chart doesn't show the true past but a past adjusted for the split Results of Operations The three months ended March 31, 2017 compared to the three months ended March 31, 2016 For the three months ended March 31, 2017 compared to the three months ended March 31, 2016, total revenues were $0 and $0, respectively, and net losses from operations were $414,663 and $26,260, respectively. The net losses were attributable to costs attributable to operating as a public company, in particular, common stock with a valuation of $390,000 that was issued to an investor relations firm in the first quarter of 2017. Going Concern As of March 31, 2017, there is substantial doubt regarding our ability to continue as a going concern as we have not generated sufficient cash flow to fund our proposed business. We have suffered recurring losses from operations since our inception. In addition, we have yet to generate an internal cash flow from our business operations or successfully raised the financing required to develop our proposed business. As a result of these and other factors, our independent auditor has expressed substantial doubt about our ability to continue as a going concern. Liquidity and Capital Resources We had no cash as of the date of March 31, 2017. Additionally, since there is no balance sheet in the last 10-Q (another bad sign), the last annual report 10-K has this balance sheet: So the company: So why did the stock value plummet? It's anyones' guess but there is no shortage of ways to justify it. In fact, it's reasonable to ask how is this company still worth $3mm ($1 * 3mm shares outstanding)...\",\n \"title\": \"\"\n },\n {\n \"docid\": \"151871\",\n \"text\": \"\\\"Their is no arbitrage opportunity with \\\"\\\"buying dividends.\\\"\\\" You're buying a taxable event. This is a largely misunderstood topic. The stock always drops by the amount if the dividend on the ex date. The stock opens that day trading \\\"\\\"ex\\\"\\\" (excluding) the dividend. It then pays out later based in the shareholders on record. There is a lot of talk about price movement and value here. That can happen but it's from trading not from the dividend per se. Yes sometimes you do see a stock pop the day prior to ex date because people are buying the stock for the dividend but the trading aspect of a stock is determined by supply and demand from people trading the stock. The dividends are paid out from the owners equity section of the balance sheet. This is a return of equity to shareholders. The idea is to give owners of the company some of their investment back (from when they bought the stock) without having the owners sell the shares of the company. After all if it's a good company you want to keep holding it so it will appreciate. Another similar way to think of it is like a bonds interest payment. People sometimes forget when trading that these are actual companies meant to be invested in. Your buying an ownership in the company with your cash. It really makes no difference to buy the dividend or not, all other things constant. Though market activity can add or lose value from trading as normal.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"506460\",\n \"text\": \"First, I want to point out that your question contains an assumption. Does anyone make significant money trading low volume stocks? I'm not sure this is the case - I've never heard of a hedge fund trading in the pink sheets, for example. Second, if your assumption is valid, here are a few ideas how it might work: Accumulate slowly, exit slowly. This won't work for short-term swings, but if you feel like a low-volume stock will be a longer-term winner, you can accumulate a sizable portion in small enough chunks not to swing the price (and then slowly unwind your position when the price has increased sufficiently). Create additional buyers/sellers. Your frustration may be one of the reasons low-volume stock is so full of scammers pumping and dumping (read any investing message board to see examples of this). If you can scare holders of the stock into selling, you can buy significant portions without driving the stock price up. Similarly, if you can convince people to buy the stock, you can unload without destroying the price. This is (of course) morally and legally dubious, so I would not recommend this practice.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"160421\",\n \"text\": \"When I read that part of his post, it reminded me more of credit companies rather than banks. People default on credit all the time. I have no idea what the regulations are on the amount of credit that a company can issue, though. And this is sort of part of what actually happened in the beginning of the economic crunch. A bunch of people began to trade for credit (debt) against what they thought the *future* value of their house or other real estate would be. After a while, people stopped being able to afford property at its future value, so they stopped buying it. When people then tried to sell their property for the future value that they had borrowed against, they couldn't, so they couldn't pay back their debt. Because real estate had become a popular investment vehicle for the middle class, this was able to reach a kind of critical mass, and shortly afterward the effects rippled back into the credit market, which also had its own crunch -- a bunch of credit just disappeared overnight because so many people had assumed a level of debt that they could not actually fulfill their promises on once the future value of their home became completely imaginary.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"365465\",\n \"text\": \"\\\"Very simple. You open an account with a broker who will do the trades for you. Then you give the broker orders to buy and sell (and the money to pay for the purchases). That's it. In the old days, you would call on the phone (remember, in all the movies, \\\"\\\"Sell, sell!!!!\\\"\\\"? That's how), now every decent broker has an online trading platform. If you don't want to have \\\"\\\"additional value\\\"\\\" and just trade - there are many online discount brokers (ETrade, ScotTrade, TD Ameritrade, and others) who offer pretty cheap trades and provide decent services and access to information. For more fees, you can also get advices and professional management where an investment manager will make the decisions for you (if you have several millions to invest, that is). After you open an account and login, you'll find a big green (usually) button which says \\\"\\\"BUY\\\"\\\". Stocks are traded on exchanges. For example the NYSE and the NASDAQ are the most common US exchanges (there's another one called \\\"\\\"pink sheets\\\"\\\", but its a different kind of animal), there are also stock exchanges in Europe (notably London, Frankfurt, Paris, Moscow) and Asia (notably Hong Kong, Shanghai, Tokyo). Many trading platforms (ETrade, that I use, for example) allow investing on some of those as well.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"593644\",\n \"text\": \"NSCC illiquid charges are charges that apply to the trading of low-priced over-the counter (OTC) securities with low volumes. Open net buy quantity represents the total unsettled share amount per stock at any given time during a 3-day settlement cycle. Open net buy quantity must be less than 5,000,000 shares per stock for your entire firm Basically, you can't hold a long position of more than 5 million shares in an illiquid OTC stock without facing a fee. You'll still be assessed this fee if you accumulate a long position of this size by breaking your purchase up into multiple transactions. Open net sell quantity represents the total unsettled share amount per stock at any given time during a 3-day settlement cycle. Open net sell quantity must be less than 10% percent of the 20-day average volume If you attempt to sell a number of shares greater than 10% of the stock's average volume over the last 20 days, you'll also be assessed a fee. The first link I included above is just an example, but it makes the important point: you may still be assessed a fee for trading OTC stocks even if your account doesn't meet the criteria because these restrictions are applied at the level of the clearing firm, not the individual client. This means that if other investors with your broker, or even at another broker that happens to use the same clearing firm, purchase more than 5 million shares in an individual OTC stock at the same time, all of your accounts may face fees, even though individually, you don't exceed the limits. Technically, these fees are assessed to the clearing firm, not the individual investor, but usually the clearing firm will pass the fees along to the broker (and possibly add other charges as well), and the broker will charge a fee to the individual account(s) that triggered the restriction. Also, remember that when buying OTC/pink sheet stocks, your ability to buy or sell is also contingent on finding someone else to buy from/sell to. If you purchase 10,000 shares one day and attempt to sell them sometime in the future, but there aren't enough buyers to buy all 10,000 from you, you might not be able to complete your order at the desired price, or even at all.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"61418\",\n \"text\": \"\\\">BPI took such a hard hit because they showed the world that they're the type of company willing to sell people really nasty shit just to make a buck (in my opinion). Honestly, if there was a news expose on 90% of the processed food that is on grocery store shelves, people would have the same reaction. You would be shocked as to what happens in food manufacturing facilities. Yes, there are FDA, USDA, and many other agencies that do both announced and surprise audits of food manufacturers to ensure food safety, but this is just a snapshot in time, and the food is only deemed as safe as to the standards of that company and what the definition of \\\"\\\"safe\\\"\\\" is. IMO, yes, BPI took a huge hit because of this being called pink slime. Are they manufacturing something that is potentially dangerous for consumption? Possibly. That all depends on who you ask what \\\"\\\"safe for consumption\\\"\\\" means. Are lobbyists involved? Bet your ass they are. But the market at the time was demanding a type of beef that was super lean. All BPI did was find a way to fulfill that need. I don't know what the outcome of this will be, but I can absolutely see both sides of the argument. The press needs to be free to report on anything and everything. However, there needs to be regulation regarding what they can and can not say from a slander standpoint. Coming up with a cute catch phrase such as \\\"\\\"pink slime\\\"\\\" is slanderous, and potentially damaging. That's where I agree with you and believe that they should have reported on the factual inclusions in the finished product. /rant\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"393925\",\n \"text\": \"Many of the major indices retreated today because of this news. Why? How do the rising budget deficits and debt relate to the stock markets? It does seem strange that there is a correlation between government debt and the stock market. But I could see many reasons for the reaction. The downgrade by S&P may make it more expensive for the government to borrow money (i.e. higher interest rates). This means it becomes more expensive for the government to borrow money and the government will probably need to raise taxes to cover the cost of borrowing. Rising taxes are not good for business. Also, many banks in the US hold US government debt. Rising yields will push down the value of their holdings which in turn will reduce the value of US debt on the businesses' balance sheets. This weakens the banks' balance sheets. They may even start to unload US bonds. Why is there such a large emphasis on the S&P rating? I don't know. I think they have proven they are practically useless. That's just my opinion. Many, though, still think they are a credible ratings agency. What happens when the debt ceiling is reached? Theoretically the government has to stop borrowing money once the debt ceiling is reached. If this occurs and the government does not raise the debt ceiling then the government faces three choices:\",\n \"title\": \"\"\n },\n {\n \"docid\": \"542765\",\n \"text\": \"Using Fundamental and Technical Analysis together is actually a good idea for longer term trading of up to 6 months or longer. The whole idea behind trading with Technical Analysis is to increase the probabilities of a trade going in the desired direction by using uncorrelated indicators that produce the same signal to buy or sell at the same time. For example, you might use a Moving Average (MA) as a buy signal when the price falls for a few days, hits the MA and then reverses and starts moving back up. If however, you also include a Stochastic Oscillator (SO) to indicate when the stock is oversold (under 20%), and if the price rebounds from the MA average at the same time as the Stochastic is crossing over in the oversold position, then this may be a higher probability trade. If you also only trade stocks that are Fundamentally healthy (as fundamentally good stocks are more likely to go up than fundamentally bad stocks) then this might increase the probabilities again. Then if you only buy when the market as a whole is moving up, then this will increase your chances again. A few weeks ago at a seminar, the presenter totalled the men in the room to be 76 and the women in the room to be 8. He then asked what will most likely be the next person to walk in the room - a man or a woman? The statistics are on the side of a wan walking in next. This is what we try to do with Technical Analysis, increase our chances when we take a trade. Of course a woman could be the next person to walk in the room, just like any trade can go against you, and this is why we use money management and risk management and take a small loss when a trade does go against you. Lets look at an example where you could incorporate FA with TA to increase your chances of profits: Above is a candlestick chart of Select Harvest (SHV), the green line above the price is the perceived value, the pink line is the 40 day MA, the blue line is the EPS, and the white lines is the Stochastic Oscillator (above 80% being overbought and below 20% is oversold). From Feb 2015 to start of Aug 2015 the stock was uptrending, since then the price reversed and started to downtrend. The stock was determined to be fundamentally good early in 2015 with the perceived value gradually increasing and greater than the share price, and the EPS starting to increase regularly from mid April. Thus, as the stock is seen as fundamentally healthy any price reversal in the vicinity of the MA could be seen as a buy opportunity. In fact there where 2 such opportunities on 31st March and 11th June where price had reversed and rebounded off the MA whist the SO crossed over in or near the oversold area. The price did reverse and then rebounded off the MA again on 9th July, however the SO was not in or near the oversold area on this occasion, so not as high in probability terms. The price still rebounded and went up again, however another momentum indicator (not shown here) shows some bearish divergence in this case - so another reason to possibly keep away at this point in time. A good signal to get out of the trade, that is your stop loss has not already taken you out, is when the price breaks and closes below the MA line. This occurred on 7th August. So if we had bought on the first signal on 31st March for $7.41 and sold when the priced broke through the MA on 7th August for $11.76, we would have made a profit of approx. 59% in just over 4 months. If bought on the second signal on 11th June for $9.98 and again sold on 7th August for $11.76, we would have made about 18% in under 2 months. So the fundamentals, the Price (in relation to MA) and the SO where all lining up to provide two high probability trades. Of course you would need to incorporate you risk management (including stops) in case the price did not continue upwards after you bought. If the market is also moving up on the day of the signal this will further increase your chances. Unless you day trade, which I would avoid, a good way to enter your trades after a signal is to enter a stop buy order after market close to buy if the price moves above the high of the signal day. That way if the market and the stock open and move lower during the day after the signal you avoid entering the trade altogether. This can be incorporated as part of your risk management and trading rules. After the price broke down through the MA we can see that a downtrend commenced which is still current today (in fact I just took a short trade on this stock yesterday). We can also see that the perceived value, whilst still above the price, has reached a peak and is currently moving downwards and the EPS after being flat for a few months has just moved down for the first time in 10 months. So maybe the fundamentals are starting to waver a bit on this stock. It may be a good stock to continue shorting into the future. So basically you can continue using Fundamental Analysis to select which stocks to buy, place them in a watch-list, and then use Technical Analysis to determine when these stocks are starting to uptrend and use a combination of uncorrelated indicators to produce higher probability signals for when to enter your trades.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"565971\",\n \"text\": \">PI’s attorney, Dan Webb, said in court Monday that ABC used the term “pink slime” 350 times over the course of its reporting, and that ABC willfully spread this preconceived, negative message. Webb also showed the jurors a picture of lean finely textured beef. “It physically doesn’t look like slime,” he said. It physically doesn't look like slime, and presumably it isn't slime chemically. What's their reason for calling it 'pink slime'? >In fact, the term “pink slime” was coined by one of the segment’s whistleblowing USDA scientists in a 2002 email to colleagues, and a 2009 New York Times piece using the term to describe BPI’s meat product won a Pulitzer Prize. So, they coined a word to describe something that was intentionally designed to sensationalize it, in a negative way. If I were on the jury this is the point of fact that I'd base my vote on. The media needs to be slapped pretty hard when they start actively damaging people and companies to sell stories.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"287325\",\n \"text\": \"\\\"What could the tax issues with the IRS be? I thought (but not totally certain) that the tax treatment of an ISO option was based on difference between exercise price and FMV at the time of the sale. This is an accounting issue. There were times not so long ago that companies actually did these things on purpose, to boost the stock grant values for their employees (especially senior employees). They would give a grant but date it with an earlier date with a more favorable valuation. This is called \\\"\\\"backdating\\\"\\\", and it brought companies down and CEOs into criminal courts. In addition, only reasonable compensation is allowed as a deduction for the company, and incorrectly set strike price may be deemed unreasonable. Thus, the deduction the company would take for your compensation can be denied, leading to loss of tax benefit (this was also a weapon used by the IRS at the time against companies doing backdating). Last but not least, company that has intentions of going public cannot allow itself such a blatant disregard of the accounting rules. Even if the mistake was not made on purpose (as it sounds), it is a mistake that has to be corrected. What should I take into consideration to determine whether a 27% increase in shares is a fair exchange for an increase in 270% increase in strike price. Did you know the strike price when you signed the contract? Was it a consideration for you? For most people, the strike price is determined at the board approval, since the valuations are not public and are not disclosed before you actually join, which is already after you've agreed to the terms. So basically, you agreed to get 100 sheets of toilet paper, and instead getting 127 sheets. So you're getting 27 sheets more than you initially agreed to. Why are you complaining? In other words, options are essentially random numbers which are quite useless. By the time you get to exercise them, they'll be diluted through a bunch of additional financing rounds, and their value will be determined for real only after the IPO, or at least when your company's stocks are trading OTC with some reasonable volume. Until then - it's just a number with not much of a meaning. The FMV does matter for early exercise and 83(b) election, if that is an option, but even then - I doubt you can actually negotiate anything.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"316673\",\n \"text\": \"We constantly hear that there are not enough trades-people to fill manufacturing roles. This is what happens when you offshore everything possible for the last 30 years. No one wants to go into a trade that will be offshored plus there are too few of those positions to apprentice in. Stop the boo-hooing big business, man-up and invest in some of your fellow citizens.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"312811\",\n \"text\": \"\\\"Share sales & purchases are accounted only on the balance sheet & cash flow statement although their effects are seen on the income statement. Remember, the balance sheet is like a snapshot in time of all accrued accounts; it's like looking at a glass of water and noting the level. The cash flow and income statements are like looking at the amount of water, \\\"\\\"actually\\\"\\\" and \\\"\\\"imaginary\\\"\\\" respectively, pumped in and out of the glass. So, when a corporation starts, it sells shares to whomever. The amount of cash received is accounted for in the investing section of the cash flow statement under the subheading \\\"\\\"issuance (retirement) of stock\\\"\\\" or the like, so when shares are sold, it is \\\"\\\"issuance\\\"\\\"; when a company buys back their shares, it's called \\\"\\\"retirement\\\"\\\", as cash inflows and outflows respectively. If you had a balance sheet before the shares were sold, you'd see under the \\\"\\\"equity\\\"\\\" heading a subheading common stock with a nominal (irrelevant) par value (this is usually something obnoxiously low like $0.01 per share used for ease of counting the shares from the Dollar amount in the account) under the subaccount almost always called \\\"\\\"common stock\\\"\\\". If you looked at the balance sheet after the sale, you'd see the number of shares in a note to the side. When shares trade publicly, the corporation usually has very little to do with it unless if they are selling or buying new shares under whatever label such as IPO, secondary offering, share repurchase, etc, but the corporation's volume from such activity would still be far below the activity of the third parties: shares are trading almost exclusively between third parties. These share sales and purchases will only be seen on the income statement under earnings per share (EPS), as EPS will rise and fall with stock repurchases and sales assuming income is held constant. While not technically part of the income statement but printed with it, the \\\"\\\"basic weighted average\\\"\\\" and \\\"\\\"diluted weighted average\\\"\\\" number of shares are also printed which are the weighted average over the reporting period of shares actually issued and expected if all promises to issue shares with employee stock options, grants, convertibles were made kept. The income statement is the accrual accounts of the operations of the company. It has little detail on investing (depreciation & appreciation) or financing (interest expenses & preferred dividends).\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"407274\",\n \"text\": \"There are lots of good points here already, but something that hasn't been mentioned yet is what would happen if the purchased items break or are somehow defective? Depending on the warranty and how trustworthy the company is, there could be an advantage to not having fully paid for the item yet when a defect is discovered, as it might incentivize the company to be more attentive to your warranty claim, since they are faced with knowing that you could stop making payments if they don't act in a timely manner. Note I'm not suggesting you stop making payments in this case, just that companies (and banks) are oftentimes more willing to work with you when you owe them money.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"301547\",\n \"text\": \"\\\"To my knowledge, there's no universal equation, so this could vary by individual/company. The equation I use (outside of sentiment measurement) is the below - which carries its own risks: This equations assumes two key points: Anything over 1.2 is considered oversold if those two conditions apply. The reason for the bear market is that that's the time stocks generally go on \\\"\\\"sale\\\"\\\" and if a company has a solid balance sheet, even in a downturn, while their profit may decrease some, a value over 1.2 could indicate the company is oversold. An example of this is Warren Buffett's investment in Wells Fargo in 2009 (around March) when WFC hit approximately 7-9 a share. Although the banking world was experiencing a crisis, Buffett saw that WFC still had a solid balance sheet, even with a decrease in profit. The missing logic with many investors was a decrease in profits - if you look at the per capita income figures, Americans lost some income, but not near enough to justify the stock falling 50%+ from its high when evaluating its business and balance sheet. The market quickly caught this too - within two months, WFC was almost at $30 a share. As an interesting side note on this, WFC now pays $1.20 dividend a year. A person who bought it at $7 a share is receiving a yield of 17%+ on their $7 a share investment. Still, this equation is not without its risks. A company may have a solid balance sheet, but end up borrowing more money while losing a ton of profit, which the investor finds out about ad-hoc (seen this happen several times). Suddenly, what \\\"\\\"appeared\\\"\\\" to be a good sale, turns into a person buying a penny with a dollar. This is why, to my knowledge, no universal equation applies, as if one did exist, every hedge fund, mutual fund, etc would be using it. One final note: with robotraders becoming more common, I'm not sure we'll see this type of opportunity again. 2009 offered some great deals, but a robotrader could easily be built with the above equation (or a similar one), meaning that as soon as we had that type of environment, all stocks fitting that scenario would be bought, pushing up their PEs. Some companies might be willing to take an \\\"\\\"all risk\\\"\\\" if they assess that this equation works for more than n% of companies (especially if that n% returns an m% that outweighs the loss). The only advantage that a small investor might have is that these large companies with robotraders are over-leveraged in bad investments and with a decline, they can't make the good investments until its too late. Remember, the equation ultimately assumes a person/company has free cash to use it (this was also a problem for many large investment firms in 2009 - they were over-leveraged in bad debt).\\\"\",\n \"title\": \"\"\n }\n]"}}},{"rowIdx":181,"cells":{"query_id":{"kind":"string","value":"896"},"query":{"kind":"string","value":"Overexpressing Cnp1 N-tail variants exacerbates the temperature-sensitive growth defect of scm3-139."},"positive_passages":{"kind":"list like","value":[{"docid":"14338915","text":"The mechanisms ensuring specific incorporation of CENP-A at centromeres are poorly understood. Mis16 and Mis18 are required for CENP-A localization at centromeres and form a complex that is conserved from fission yeast to human. Fission yeast sim1 mutants that alleviate kinetochore domain silencing are defective in Scm3(Sp), the ortholog of budding yeast Scm3(Sc). Scm3(Sp) depends on Mis16/18 for its centromere localization and like them is recruited to centromeres in late anaphase. Importantly, Scm3(Sp) coaffinity purifies with CENP-A(Cnp1) and associates with CENP-A(Cnp1) in vitro, yet localizes independently of intact CENP-A(Cnp1) chromatin and is differentially released from chromatin. While Scm3(Sc) has been proposed to form a unique hexameric nucleosome with CENP-A(Cse4) and histone H4 at budding yeast point centromeres, we favor a model in which Scm3(Sp) acts as a CENP-A(Cnp1) receptor/assembly factor, cooperating with Mis16 and Mis18 to receive CENP-A(Cnp1) from the Sim3 escort and mediate assembly of CENP-A(Cnp1) into subkinetochore chromatin.","title":"Fission Yeast Scm3: A CENP-A Receptor Required for Integrity of Subkinetochore Chromatin"}],"string":"[\n {\n \"docid\": \"14338915\",\n \"text\": \"The mechanisms ensuring specific incorporation of CENP-A at centromeres are poorly understood. Mis16 and Mis18 are required for CENP-A localization at centromeres and form a complex that is conserved from fission yeast to human. Fission yeast sim1 mutants that alleviate kinetochore domain silencing are defective in Scm3(Sp), the ortholog of budding yeast Scm3(Sc). Scm3(Sp) depends on Mis16/18 for its centromere localization and like them is recruited to centromeres in late anaphase. Importantly, Scm3(Sp) coaffinity purifies with CENP-A(Cnp1) and associates with CENP-A(Cnp1) in vitro, yet localizes independently of intact CENP-A(Cnp1) chromatin and is differentially released from chromatin. While Scm3(Sc) has been proposed to form a unique hexameric nucleosome with CENP-A(Cse4) and histone H4 at budding yeast point centromeres, we favor a model in which Scm3(Sp) acts as a CENP-A(Cnp1) receptor/assembly factor, cooperating with Mis16 and Mis18 to receive CENP-A(Cnp1) from the Sim3 escort and mediate assembly of CENP-A(Cnp1) into subkinetochore chromatin.\",\n \"title\": \"Fission Yeast Scm3: A CENP-A Receptor Required for Integrity of Subkinetochore Chromatin\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"10189634","text":"CENP-A chromatin forms the foundation for kinetochore assembly. Replication-independent incorporation of CENP-A at centromeres depends on its chaperone HJURP(Scm3), and Mis18 in vertebrates and fission yeast. The recruitment of Mis18 and HJURP(Scm3) to centromeres is cell cycle regulated. Vertebrate Mis18 associates with Mis18BP1(KNL2), which is critical for the recruitment of Mis18 and HJURP(Scm3). We identify two novel fission yeast Mis18-interacting proteins (Eic1 and Eic2), components of the Mis18 complex. Eic1 is essential to maintain Cnp1(CENP-A) at centromeres and is crucial for kinetochore integrity; Eic2 is dispensable. Eic1 also associates with Fta7(CENP-Q/Okp1), Cnl2(Nkp2) and Mal2(CENP-O/Mcm21), components of the constitutive CCAN/Mis6/Ctf19 complex. No Mis18BP1(KNL2) orthologue has been identified in fission yeast, consequently it remains unknown how the key Cnp1(CENP-A) loading factor Mis18 is recruited. Our findings suggest that Eic1 serves a function analogous to that of Mis18BP1(KNL2), thus representing the functional counterpart of Mis18BP1(KNL2) in fission yeast that connects with a module within the CCAN/Mis6/Ctf19 complex to allow the temporally regulated recruitment of the Mis18/Scm3(HJURP) Cnp1(CENP-A) loading factors. The novel interactions identified between CENP-A loading factors and the CCAN/Mis6/Ctf19 complex are likely to also contribute to CENP-A maintenance in other organisms.","title":"Eic1 links Mis18 with the CCAN/Mis6/Ctf19 complex to promote CENP-A assembly"},{"docid":"16686383","text":"The centromeric histone H3 variant (CenH3) is essential for chromosome segregation in eukaryotes. We identify posttranslational modifications of Saccharomyces cerevisiae CenH3, Cse4. Functional characterization of cse4 phosphorylation mutants shows growth and chromosome segregation defects when combined with kinetochore mutants okp1 and ame1. Using a phosphoserine-specific antibody, we show that the association of phosphorylated Cse4 with centromeres increases in response to defective microtubule attachment or reduced cohesion. We determine that evolutionarily conserved Ipl1/Aurora B contributes to phosphorylation of Cse4, as levels of phosphorylated Cse4 are reduced at centromeres in ipl1 strains in vivo, and in vitro assays show phosphorylation of Cse4 by Ipl1. Consistent with these results, we observe that a phosphomimetic cse4-4SD mutant suppresses the temperature-sensitive growth of ipl1-2 and Ipl1 substrate mutants dam1 spc34 and ndc80, which are defective for chromosome biorientation. Furthermore, cell biology approaches using a green fluorescent protein-labeled chromosome show that cse4-4SD suppresses chromosome segregation defects in dam1 spc34 strains. On the basis of these results, we propose that phosphorylation of Cse4 destabilizes defective kinetochores to promote biorientation and ensure faithful chromosome segregation. Taken together, our results provide a detailed analysis, in vivo and in vitro, of Cse4 phosphorylation and its role in promoting faithful chromosome segregation.","title":"Phosphorylation of centromeric histone H3 variant regulates chromosome segregation in Saccharomyces cerevisiae"},{"docid":"21425864","text":"Glycosyl phosphatidylinositols (GPIs) anchor many proteins to the surface of eukaryotic cells and may also serve as sorting signals on proteins and participate in signal transduction. We have isolated a Saccharomyces cerevisiae GPI anchoring mutant, gpi1, using a colony screen for cells blocked in [3H]inositol incorporation into protein. The gpi1 mutant is defective in vitro in the synthesis of N-acetylglucosaminyl phosphatidylinositol, the first intermediate in GPI synthesis, and is also temperature-sensitive for growth. Completion of the first step in GPI assembly is therefore required for growth of the unicellular eukaryote S. cerevisiae. GPI synthesis could therefore be exploited as a target for antifungal or antiparasitic agents.","title":"A conditionally lethal yeast mutant blocked at the first step in glycosyl phosphatidylinositol anchor synthesis."},{"docid":"26117607","text":"Down syndrome cell adhesion molecule (Dscam) seems likely to play a key role in the \"alternative adaptive immunity\" that has been reported in invertebrates. Dscam consists of a cytoplasmic tail that is involved in signal transduction and a hypervariable extracellular region that might use a pathogen recognition mechanism similar to that used by the vertebrate antibodies. In our previous paper, we isolated a unique tail-less form of Dscam from Litopenaeus vannamei. In this study, we report the first membrane-bound form of shrimp Dscam: PmDscam was isolated from Penaeus monodon, and it occurred in both membrane-bound and tail-less forms. Phylogenetic analysis showed that while the crustacean Dscams from shrimp and water flea did not share a single subclade, they were distinct from the invertebrate Dscam-like molecules and from the insecta Dscams. In the extracellular region, the variable regions of PmDscam were located in N-terminal Ig2, N-terminal Ig3 and the entire Ig7 domain. The PmDscam extracellular variants and transmembrane domain variants were produced by mutually exclusive alternative splicing events. The cytoplasmic tail variants were produced by exon inclusion/exclusion. Based on the genomic organization of Daphnia Dscam's cytoplasmic tail, we propose a model of how the shrimp Dscam genomic locus might use Type III polyadenylation to generate both the tail-less and membrane-bound forms.","title":"Penaeus monodon Dscam (PmDscam) has a highly diverse cytoplasmic tail and is the first membrane-bound shrimp Dscam to be reported."},{"docid":"17671145","text":"The androgen receptor (AR) is overexpressed and hyperactivated in human castration-resistant prostate cancer (CRPC). However, the determinants of AR overexpression in CRPC are poorly defined. Here we show that retinoic acid receptor-related orphan receptor γ (ROR-γ) is overexpressed and amplified in metastatic CRPC tumors, and that ROR-γ drives AR expression in the tumors. ROR-γ recruits nuclear receptor coactivator 1 and 3 (NCOA1 and NCOA3, also known as SRC-1 and SRC-3) to an AR-ROR response element (RORE) to stimulate AR gene transcription. ROR-γ antagonists suppress the expression of both AR and its variant AR-V7 in prostate cancer (PCa) cell lines and tumors. ROR-γ antagonists also markedly diminish genome-wide AR binding, H3K27ac abundance and expression of the AR target gene network. Finally, ROR-γ antagonists suppressed tumor growth in multiple AR-expressing, but not AR-negative, xenograft PCa models, and they effectively sensitized CRPC tumors to enzalutamide, without overt toxicity, in mice. Taken together, these results establish ROR-γ as a key player in CRPC by acting upstream of AR and as a potential therapeutic target for advanced PCa.","title":"ROR-γ drives androgen receptor expression and represents a therapeutic target in castration-resistant prostate cancer"},{"docid":"4312169","text":"Glioblastoma multiforme (GBM) is a lethal brain tumour in adults and children. However, DNA copy number and gene expression signatures indicate differences between adult and paediatric cases. To explore the genetic events underlying this distinction, we sequenced the exomes of 48 paediatric GBM samples. Somatic mutations in the H3.3-ATRX-DAXX chromatin remodelling pathway were identified in 44% of tumours (21/48). Recurrent mutations in H3F3A, which encodes the replication-independent histone 3 variant H3.3, were observed in 31% of tumours, and led to amino acid substitutions at two critical positions within the histone tail (K27M, G34R/G34V) involved in key regulatory post-translational modifications. Mutations in ATRX (α-thalassaemia/mental retardation syndrome X-linked) and DAXX (death-domain associated protein), encoding two subunits of a chromatin remodelling complex required for H3.3 incorporation at pericentric heterochromatin and telomeres, were identified in 31% of samples overall, and in 100% of tumours harbouring a G34R or G34V H3.3 mutation. Somatic TP53 mutations were identified in 54% of all cases, and in 86% of samples with H3F3A and/or ATRX mutations. Screening of a large cohort of gliomas of various grades and histologies (n = 784) showed H3F3A mutations to be specific to GBM and highly prevalent in children and young adults. Furthermore, the presence of H3F3A/ATRX-DAXX/TP53 mutations was strongly associated with alternative lengthening of telomeres and specific gene expression profiles. This is, to our knowledge, the first report to highlight recurrent mutations in a regulatory histone in humans, and our data suggest that defects of the chromatin architecture underlie paediatric and young adult GBM pathogenesis.","title":"Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma"},{"docid":"13293033","text":"Down syndrome (DS) is the most frequent cause of human congenital mental retardation. Cognitive deficits in DS result from perturbations of normal cellular processes both during development and in adult tissues, but the mechanisms underlying DS etiology remain poorly understood. To assess the ability of induced pluripotent stem cells (iPSCs) to model DS phenotypes, as a prototypical complex human disease, we generated bona fide DS and wild-type (WT) nonviral iPSCs by episomal reprogramming. DS iPSCs selectively overexpressed chromosome 21 genes, consistent with gene dosage, which was associated with deregulation of thousands of genes throughout the genome. DS and WT iPSCs were neurally converted at >95% efficiency and had remarkably similar lineage potency, differentiation kinetics, proliferation, and axon extension at early time points. However, at later time points DS cultures showed a twofold bias toward glial lineages. Moreover, DS neural cultures were up to two times more sensitive to oxidative stress-induced apoptosis, and this could be prevented by the antioxidant N-acetylcysteine. Our results reveal a striking complexity in the genetic alterations caused by trisomy 21 that are likely to underlie DS developmental phenotypes, and indicate a central role for defective early glial development in establishing developmental defects in DS brains. Furthermore, oxidative stress sensitivity is likely to contribute to the accelerated neurodegeneration seen in DS, and we provide proof of concept for screening corrective therapeutics using DS iPSCs and their derivatives. Nonviral DS iPSCs can therefore model features of complex human disease in vitro and provide a renewable and ethically unencumbered discovery platform.","title":"Integration-free induced pluripotent stem cells model genetic and neural developmental features of down syndrome etiology."},{"docid":"26625002","text":"The outer membrane channel TolC is a key component of multidrug efflux and type I secretion transporters in Escherichia coli. Mutational inactivation of TolC renders cells highly susceptible to antibiotics and leads to defects in secretion of protein toxins. Despite impairment of various transport functions, no growth defects were reported in cells lacking TolC. Unexpectedly, we found that the loss of TolC notably impairs cell division and growth in minimal glucose medium. The TolC-dependent phenotype was further exacerbated by the loss of ygiB and ygiC genes expressed in the same operon as tolC and their homologues yjfM and yjfC located elsewhere on the chromosome. Our results show that this growth deficiency is caused by depletion of the critical metabolite NAD(+) and high NADH/NAD(+) ratios. The increased amounts of PspA and decreased rates of NADH oxidation in Delta tolC membranes indicated stress on the membrane and dissipation of a proton motive force. We conclude that inactivation of TolC triggers metabolic shutdown in E. coli cells grown in minimal glucose medium. The Delta tolC phenotype is partially rescued by YgiBC and YjfMC, which have parallel functions independent from TolC.","title":"Metabolic shutdown in Escherichia coli cells lacking the outer membrane channel TolC."},{"docid":"24725136","text":"BACKGROUND The combination of ataxia and hypogonadism was first described more than a century ago, but its genetic basis has remained elusive. METHODS We performed whole-exome sequencing in a patient with ataxia and hypogonadotropic hypogonadism, followed by targeted sequencing of candidate genes in similarly affected patients. Neurologic and reproductive endocrine phenotypes were characterized in detail. The effects of sequence variants and the presence of an epistatic interaction were tested in a zebrafish model. RESULTS Digenic homozygous mutations in RNF216 and OTUD4, which encode a ubiquitin E3 ligase and a deubiquitinase, respectively, were found in three affected siblings in a consanguineous family. Additional screening identified compound heterozygous truncating mutations in RNF216 in an unrelated patient and single heterozygous deleterious mutations in four other patients. Knockdown of rnf216 or otud4 in zebrafish embryos induced defects in the eye, optic tectum, and cerebellum; combinatorial suppression of both genes exacerbated these phenotypes, which were rescued by nonmutant, but not mutant, human RNF216 or OTUD4 messenger RNA. All patients had progressive ataxia and dementia. Neuronal loss was observed in cerebellar pathways and the hippocampus; surviving hippocampal neurons contained ubiquitin-immunoreactive intranuclear inclusions. Defects were detected at the hypothalamic and pituitary levels of the reproductive endocrine axis. CONCLUSIONS The syndrome of hypogonadotropic hypogonadism, ataxia, and dementia can be caused by inactivating mutations in RNF216 or by the combination of mutations in RNF216 and OTUD4. These findings link disordered ubiquitination to neurodegeneration and reproductive dysfunction and highlight the power of whole-exome sequencing in combination with functional studies to unveil genetic interactions that cause disease. (Funded by the National Institutes of Health and others.).","title":"Ataxia, dementia, and hypogonadotropism caused by disordered ubiquitination."},{"docid":"7717468","text":"Microbial survival in a host is usually dependent on the ability of a pathogen to undergo changes that promote escape from host defense mechanisms. The human-pathogenic fungus Cryptococcus neoformans undergoes phenotypic switching in vivo that promotes persistence in tissue. By microarray and real-time PCR analyses, the allergen 1 gene (ALL1) was found to be downregulated in the hypervirulent mucoid switch variant, both during logarithmic growth and during intracellular growth in macrophages. The ALL1 gene encodes a small cytoplasmic protein that is involved in capsule formation. Growth of an all1Delta gene deletion mutant was normal. Similar to cells of the mucoid switch variant, all1Delta cells produced a larger polysaccharide capsule than cells of the smooth parent and the complemented strain produced, and the enlarged capsule inhibited macrophage phagocytosis. The mutant exhibited a modest defect in capsule induction compared to all of the other variants. In animal models the phenotype of the all1Delta mutant mimicked the hypervirulent phenotype of the mucoid switch variant, which is characterized by decreased host survival and elevated intracranial pressure. Decreased survival is likely the result of both an ineffective cell-mediated immune response and impaired phagocytosis by macrophages. Consequently, we concluded that, unlike loss of most virulence-associated genes, where loss of gene function results in attenuated virulence, loss of the ALL1 gene enhances virulence by altering the host-pathogen interaction and thereby impairing clearance. Our data identified the first cryptococcal gene associated with elevated intracranial pressure and support the hypothesis that an environmental opportunistic pathogen has modified its virulence in vivo by epigenetic downregulation of gene function.","title":"Loss of allergen 1 confers a hypervirulent phenotype that resembles mucoid switch variants of Cryptococcus neoformans."},{"docid":"14471161","text":"Circadian disruption accelerates cancer progression, whereas circadian reinforcement could halt it. Mice with P03 pancreatic adenocarcinoma (n = 77) were synchronized and fed ad libitum (AL) or with meal timing (MT) from Zeitgeber time (ZT) 2 to ZT6 with normal or fat diet. Tumor gene expression profiling was determined with DNA microarrays at endogenous circadian time (CT) 4 and CT16. Circadian mRNA expression patterns were determined for clock genes Rev-erbalpha, Per2, and Bmal1, cellular stress genes Hspa8 and Cirbp, and cyclin A2 gene Ccna2 in liver and tumor. The 24-hour patterns in telemetered rest-activity and body temperature and plasma corticosterone and insulin-like growth factor-I (IGF-I) were assessed. We showed that MT inhibited cancer growth by approximately 40% as compared with AL (P = 0.011) irrespective of calorie intake. Clock gene transcription remained arrhythmic in tumors irrespective of feeding schedule or diet. Yet, MT upregulated or downregulated the expression of 423 tumor genes, according to CT. Moreover, 36 genes involved in cellular stress, cell cycle, and metabolism were upregulated at one CT and downregulated 12 h apart. MT induced >10-fold circadian expression of Hspa8, Cirbp, and Ccna2 in tumors. Corticosterone or IGF-I patterns played no role in tumor growth inhibition. In contrast, MT consistently doubled the circadian amplitude of body temperature. Peak and trough respectively corresponded to peak expressions of Hspa8 and Cirbp in tumors. The reinforcement of the host circadian timing system with MT induced 24-hour rhythmic expression of critical genes in clock-deficient tumors, which translated into cancer growth inhibition. Targeting circadian clocks represents a novel potential challenge for cancer therapeutics.","title":"Cancer inhibition through circadian reprogramming of tumor transcriptome with meal timing."},{"docid":"29564505","text":"IMPORTANCE Exacerbations of respiratory symptoms in chronic obstructive pulmonary disease (COPD) have profound and long-lasting adverse effects on patients. OBJECTIVE To test the hypothesis that elevated levels of inflammatory biomarkers in individuals with stable COPD are associated with an increased risk of having exacerbations. DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study examining 61,650 participants with spirometry measurements from the Copenhagen City Heart Study (2001-2003) and the Copenhagen General Population Study (2003-2008). Of these, 6574 had COPD, defined as a ratio between forced expiratory volume in 1 second (FEV1) and forced vital capacity below 0.7. MAIN OUTCOMES AND MEASURES Baseline levels of C-reactive protein (CRP) and fibrinogen and leukocyte count were measured in participants at a time when they were not experiencing symptoms of exacerbations. Exacerbations were recorded and defined as short-course treatment with oral corticosteroids alone or in combination with an antibiotic or as a hospital admission due to COPD. Levels of CRP and fibrinogen and leukocyte count were defined as high or low according to cut points of 3 mg/L, 14 μmol/L, and 9 ×10(9)/L, respectively. RESULTS During follow-up, 3083 exacerbations were recorded (mean, 0.5/participant). In the first year of follow-up, multivariable-adjusted odds ratios for having frequent exacerbations were 1.2 (95% CI, 0.7-2.2; 17 events/1000 person-years) for individuals with 1 high biomarker, 1.7 (95% CI, 0.9-3.2; 32 events/1000 person-years) for individuals with 2 high biomarkers, and 3.7 (95% CI, 1.9-7.4; 81 events/1000 person-years) for individuals with 3 high biomarkers compared with individuals who had no elevated biomarkers (9 events/1000 person-years; trend: P = 2 × 10(-5)). Corresponding hazard ratios using maximum follow-up time were 1.4 (95% CI, 1.1-1.8), 1.6 (95% CI, 1.3-2.2), and 2.5 (95% CI, 1.8-3.4), respectively (trend: P = 1 × 10(-8)). The addition of inflammatory biomarkers to a basic model including age, sex, FEV1 percent predicted, smoking, use of any inhaled medication, body mass index, history of previous exacerbations, and time since most recent prior exacerbation improved the C statistics from 0.71 to 0.73 (comparison: P = 9 × 10(-5)). Relative risks were consistent in those with milder COPD, in those with no history of frequent exacerbations, and in the 2 studies separately. The highest 5-year absolute risks of having frequent exacerbations in those with 3 high biomarkers (vs no high biomarkers) were 62% (vs 24%) for those with Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades C-D (n = 558), 98% (vs 64%) in those with a history of frequent exacerbations (n = 127), and 52% (vs 15%) for those with GOLD grades 3-4 (n = 465). CONCLUSIONS AND RELEVANCE Simultaneously elevated levels of CRP and fibrinogen and leukocyte count in individuals with COPD were associated with increased risk of having exacerbations, even in those with milder COPD and in those without previous exacerbations. Further investigation is needed to determine the clinical value of these biomarkers for risk stratification.","title":"Inflammatory biomarkers and exacerbations in chronic obstructive pulmonary disease."},{"docid":"23117928","text":"Infection of Sulfolobus islandicus REY15A with mixtures of different Sulfolobus viruses, including STSV2, did not induce spacer acquisition by the host CRISPR immune system. However, coinfection with the tailed fusiform viruses SMV1 and STSV2 generated hyperactive spacer acquisition in both CRISPR loci, exclusively from STSV2, with the resultant loss of STSV2 but not SMV1. SMV1 was shown to activate adaptation while itself being resistant to CRISPR-mediated adaptation and DNA interference. Exceptionally, a single clone S-1 isolated from an SMV1 + STSV2-infected culture, that carried STSV2-specific spacers and had lost STSV2 but not SMV1, acquired spacers from SMV1. This effect was also reproducible on reinfecting wild-type host cells with a variant SMV1 isolated from the S-1 culture. The SMV1 variant lacked a virion protein ORF114 that was shown to bind DNA. This study also provided evidence for: (i) limits on the maximum sizes of CRISPR loci; (ii) spacer uptake strongly retarding growth of infected cultures; (iii) protospacer selection being essentially random and non-directional, and (iv) the reversible uptake of spacers from STSV2 and SMV1. A hypothesis is presented to explain the interactive conflicts between SMV1 and the host CRISPR immune system.","title":"Inter-viral conflicts that exploit host CRISPR immune systems of Sulfolobus."},{"docid":"6766459","text":"Fever is commonly used to diagnose disease and is consistently associated with increased mortality in critically ill patients. However, the molecular controls of elevated body temperature are poorly understood. We discovered that the expression of RNA-binding motif protein 3 (RBM3), known to respond to cold stress and to modulate microRNA (miRNA) expression, was reduced in 30 patients with fever, and in THP-1-derived macrophages maintained at a fever-like temperature (40 °C). Notably, RBM3 expression is reduced during fever whether or not infection is demonstrable. Reduced RBM3 expression resulted in increased expression of RBM3-targeted temperature-sensitive miRNAs, we termed thermomiRs. ThermomiRs such as miR-142-5p and miR-143 in turn target endogenous pyrogens including IL-6, IL6ST, TLR2, PGE2 and TNF to complete a negative feedback mechanism, which may be crucial to prevent pathological hyperthermia. Using normal PBMCs that were exogenously exposed to fever-like temperature (40 °C), we further demonstrate the trend by which decreased levels of RBM3 were associated with increased levels of miR-142-5p and miR-143 and vice versa over a 24 h time course. Collectively, our results indicate the existence of a negative feedback loop that regulates fever via reduced RBM3 levels and increased expression of miR-142-5p and miR-143.","title":"RBM3 regulates temperature sensitive miR-142–5p and miR-143 (thermomiRs), which target immune genes and control fever"},{"docid":"26596106","text":"In the yeast S. cerevisiae, ribosome assembly is linked to environmental conditions by the coordinate transcriptional regulation of genes required for ribosome biogenesis. In this study we show that two nonessential stress-responsive genes, YAR1 and LTV1, function in 40S subunit production. We provide genetic and biochemical evidence that Yar1, a small ankyrin-repeat protein, physically interacts with RpS3, a component of the 40S subunit, and with Ltv1, a protein recently identified as a substoichiometric component of a 43S preribosomal particle. We demonstrate that cells lacking YAR1 or LTV1 are hypersensitive to particular protein synthesis inhibitors and exhibit aberrant polysome profiles, with a reduced absolute number of 40S subunits and an excess of free 60S subunits. Surprisingly, both mutants are also hypersensitive to a variety of environmental stress conditions. Overexpression of RPS3 suppresses both the stress sensitivity and the ribosome biogenesis defect of Deltayar1 mutants, but does not suppress either defect in Deltaltv1 mutants. We propose that YAR1 and LTV1 play distinct, nonessential roles in 40S subunit production. The stress-sensitive phenotypes of strains lacking these genes reveal a hitherto unknown link between ribosome biogenesis factors and environmental stress sensitivity.","title":"Genetic and biochemical interactions among Yar1, Ltv1 and Rps3 define novel links between environmental stress and ribosome biogenesis in Saccharomyces cerevisiae."},{"docid":"34016944","text":"PURPOSE Tyrosine kinase (TK) inhibitors are emerging as a promising new approach to the treatment of HER overexpressing tumors, however optimal use of these agents awaits further definition of the downstream signaling pathways that mediate their effects. We reported previously that both EGFR- and Her2-overexpressing tumors are sensitive to the new EGFR-selective TK inhibitor gefitinib (ZD1839, \"Iressa\"), and sensitivity to this agent correlated with its ability to down-regulate Akt. However, EGFR-overexpressing MDA-468 cells, which lack PTEN function, are resistant to ZD1839, and ZD1839 is unable to down-regulate Akt activity in these cells. EXPERIMENTAL DESIGN To study the role of PTEN function, we generated MDA468 cells with tet-inducible PTEN expression. RESULTS We show here that the resistance of MDA-468 cells to ZD1839 is attributable to EGFR-independent constitutive Akt activation caused by loss of PTEN function in these cells. Reconstitution of PTEN function through tet-inducible expression restores ZD1839 sensitivity to these cells and reestablishes EGFR-stimulated Akt signaling. Although restoration of PTEN function to tumors is difficult to implement clinically, much of the effects of PTEN loss are attributable to overactive PI3K/Akt pathway signaling, and this overactivity can be modulated by pharmacologic approaches. We show here that pharmacologic down-regulation of constitutive PI3K/Akt pathway signaling using the PI3K inhibitor LY294002 similarly restores EGFR-stimulated Akt signaling and sensitizes MDA-468 cells to ZD1839. CONCLUSIONS Sensitivity to ZD1839 requires intact growth factor receptor-stimulated Akt signaling activity. PTEN loss leads to uncoupling of this signaling pathway and results in ZD1839 resistance, which can be reversed with reintroduction of PTEN or pharmacologic down-regulation of constitutive PI3K/Akt pathway activity. These data have important predictive and therapeutic clinical implications.","title":"Resistance to gefitinib in PTEN-null HER-overexpressing tumor cells can be overcome through restoration of PTEN function or pharmacologic modulation of constitutive phosphatidylinositol 3'-kinase/Akt pathway signaling."},{"docid":"22362025","text":"Small regulatory RNAs are key regulators of gene expression. One class of small regulatory RNAs, termed the endogenous small interfering RNAs (endo siRNAs), is thought to negatively regulate cellular transcripts via an RNA interference (RNAi)-like mechanism termed endogenous RNAi (endo RNAi). A complex of proteins composed of ERI-1/3/5, RRF-3, and DICER (the ERI/DICER complex) mediates endo RNAi processes in Caenorhabditis elegans. We conducted a genetic screen to identify additional components of the endo RNAi machinery. Our screen recovered alleles of eri-9, which encodes a novel DICER-interacting protein, and a missense mutation within the helicase domain of DICER [DCR-1(G492R)]. ERI-9(-) and DCR-1(G492) animals exhibit defects in endo siRNA expression and a concomitant failure to regulate mRNAs that exhibit sequence homology to these endo siRNAs, indicating that ERI-9 and the DCR-1 helicase domain function in the C. elegans endo RNAi pathway. We define a subset of Eri mutant animals (including eri-1, rrf-3, eri-3, and dcr-1, but not eri-9 or ergo-1) that exhibit temperature-sensitive, sperm-specific sterility and defects in X chromosome segregation. Among these mutants we find multiple aberrations in sperm development beginning with cytokinesis and extending through terminal differentiation. These results identify novel components of the endo RNAi machinery, demonstrate differential requirements for the Eri factors in the sperm-producing germline, and begin to delineate the functional requirement for the ERI/DICER complex in sperm development.","title":"Requirement for the ERI/DICER complex in endogenous RNA interference and sperm development in Caenorhabditis elegans."},{"docid":"9315213","text":"BACKGROUND Fibroblast growth factor 21 (FGF21) is a metabolic hormone with pleiotropic effects on glucose and lipid metabolism and insulin sensitivity. It acts as a key downstream target of both peroxisome proliferator-activated receptor α and γ, the agonists of which have been used for lipid lowering and insulin sensitization, respectively. However, the role of FGF21 in the cardiovascular system remains elusive. METHODS AND RESULTS The roles of FGF21 in atherosclerosis were investigated by evaluating the impact of FGF21 deficiency and replenishment with recombinant FGF21 in apolipoprotein E(-/-) mice. FGF21 deficiency causes a marked exacerbation of atherosclerotic plaque formation and premature death in apolipoprotein E(-/-) mice, which is accompanied by hypoadiponectinemia and severe hypercholesterolemia. Replenishment of FGF21 protects against atherosclerosis in apolipoprotein E(-/-)mice via 2 independent mechanisms, inducing the adipocyte production of adiponectin, which in turn acts on the blood vessels to inhibit neointima formation and macrophage inflammation, and suppressing the hepatic expression of the transcription factor sterol regulatory element-binding protein-2, thereby leading to reduced cholesterol synthesis and attenuation of hypercholesterolemia. Chronic treatment with adiponectin partially reverses atherosclerosis without obvious effects on hypercholesterolemia in FGF21-deficient apolipoprotein E(-/-) mice. By contrast, the cholesterol-lowering effects of FGF21 are abrogated by hepatic expression of sterol regulatory element-binding protein-2. CONCLUSIONS FGF21 protects against atherosclerosis via fine tuning the multiorgan crosstalk among liver, adipose tissue, and blood vessels.","title":"Fibroblast Growth Factor 21 Prevents Atherosclerosis by Suppression of Hepatic Sterol Regulatory Element-Binding Protein-2 and Induction of Adiponectin in Mice"},{"docid":"10169908","text":"PURPOSE We have previously identified solute-linked carrier family A1 member 5 (SLC1A5) as an overexpressed protein in a shotgun proteomic analysis of stage I non-small cell lung cancer (NSCLC) when compared with matched controls. We hypothesized that overexpression of SLC1A5 occurs to meet the metabolic demand for lung cancer cell growth and survival. EXPERIMENTAL DESIGN To test our hypothesis, we first analyzed the protein expression of SLC1A5 in archival lung cancer tissues by immunohistochemistry and immunoblotting (N = 98) and in cell lines (N = 36). To examine SLC1A5 involvement in amino acid transportation, we conducted kinetic analysis of l-glutamine (Gln) uptake in lung cancer cell lines in the presence and absence of a pharmacologic inhibitor of SLC1A5, gamma-l-Glutamyl-p-Nitroanilide (GPNA). Finally, we examined the effect of Gln deprivation and uptake inhibition on cell growth, cell-cycle progression, and growth signaling pathways of five lung cancer cell lines. RESULTS Our results show that (i) SLC1A5 protein is expressed in 95% of squamous cell carcinomas (SCC), 74% of adenocarcinomas (ADC), and 50% of neuroendocrine tumors; (ii) SLC1A5 is located at the cytoplasmic membrane and is significantly associated with SCC histology and male gender; (iii) 68% of Gln is transported in a Na(+)-dependent manner, 50% of which is attributed to SLC1A5 activity; and (iv) pharmacologic and genetic targeting of SLC1A5 decreased cell growth and viability in lung cancer cells, an effect mediated in part by mTOR signaling. CONCLUSIONS These results suggest that SLC1A5 plays a key role in Gln transport controlling lung cancer cells' metabolism, growth, and survival.","title":"SLC1A5 mediates glutamine transport required for lung cancer cell growth and survival."},{"docid":"22522432","text":"The stable contact of ISW2 with nucleosomal DNA approximately 20 bp from the dyad was shown by DNA footprinting and photoaffinity labeling using recombinant histone octamers to require the histone H4 N-terminal tail. Efficient ISW2 remodeling also required the H4 N-terminal tail, although the lack of the H4 tail can be mostly compensated for by increasing the incubation time or concentration of ISW2. Similarly, the length of extranucleosomal DNA affected the stable contact of ISW2 with this same internal nucleosomal site, with the optimal length being 70 to 85 bp. These data indicate the histone H4 tail, in concert with a favorable length of extranucleosomal DNA, recruits and properly orients ISW2 onto the nucleosome for efficient nucleosome remodeling. One consequence of this property of ISW2 is likely its previously observed nucleosome spacing activity.","title":"Regulation of ISW2 by concerted action of histone H4 tail and extranucleosomal DNA."},{"docid":"12225214","text":"Ubiquitination controls a broad range of cellular functions. The last step of the ubiquitination pathway is regulated by enzyme type 3 (E3) ubiquitin ligases. E3 enzymes are responsible for substrate specificity and catalyze the formation of an isopeptide bond between a lysine residue of the substrate (or the N terminus of the substrate) and ubiquitin. MIR1 and MIR2 are two E3 ubiquitin ligases encoded by Kaposi's sarcoma-associated herpesvirus that mediate the ubiquitination of major histocompatibility complex class I (MHC I) molecules and subsequent internalization. Here, we found that MIR1, but not MIR2, promoted down-regulation of MHC I molecules lacking lysine residues in their intracytoplasmic domain. In the presence of MIR1, these MHC I molecules were ubiquitinated, and their association with ubiquitin was sensitive to beta2-mercaptoethanol, unlike lysine-ubiquitin bonds. This form of ubiquitination required a cysteine residue in the intracytoplasmic tail of MHC I molecules. An MHC I molecule containing a single cysteine residue in an artificial glycine and alanine intracytoplasmic domain was endocytosed and degraded in the presence of MIR1. Thus, ubiquitination can occur on proteins lacking accessible lysines or an accessible N terminus.","title":"Ubiquitination on nonlysine residues by a viral E3 ubiquitin ligase."},{"docid":"435529","text":"HEN1-mediated 2'-O-methylation has been shown to be a key mechanism to protect plant microRNAs (miRNAs) and small interfering RNAs (siRNAs) as well as animal piwi-interacting RNAs (piRNAs) from degradation and 3' terminal uridylation [1-8]. However, enzymes uridylating unmethylated miRNAs, siRNAs, or piRNAs in hen1 are unknown. In this study, a genetic screen identified a second-site mutation hen1 suppressor1-2 (heso1-2) that partially suppresses the morphological phenotypes of the hypomorphic hen1-2 allele and the null hen1-1 allele in Arabidopsis. HESO1 encodes a terminal nucleotidyl transferase that prefers to add untemplated uridine to the 3' end of RNA, which is completely abolished by 2'-O-methylation. heso1-2 affects the profile of u-tailed miRNAs and siRNAs and increases the abundance of truncated and/or normal sized ones in hen1, which often results in increased total amount of miRNAs and siRNAs in hen1. In contrast, overexpressing HESO1 in hen1-2 causes more severe morphological defects and less accumulation of miRNAs. These results demonstrate that HESO1 is an enzyme uridylating unmethylated miRNAs and siRNAs in hen1. These observations also suggest that uridylation may destabilize unmethylated miRNAs through an unknown mechanism and compete with 3'-to-5' exoribonuclease activities in hen1. This study shall have implications on piRNA uridylation in hen1 in animals.","title":"Uridylation of miRNAs by HEN1 SUPPRESSOR1 in Arabidopsis"},{"docid":"4455466","text":"Recognition of modified histones by ‘reader’ proteins plays a critical role in the regulation of chromatin. H3K36 trimethylation (H3K36me3) is deposited onto the nucleosomes in the transcribed regions after RNA polymerase II elongation. In yeast, this mark in turn recruits epigenetic regulators to reset the chromatin to a relatively repressive state, thus suppressing cryptic transcription. However, much less is known about the role of H3K36me3 in transcription regulation in mammals. This is further complicated by the transcription-coupled incorporation of the histone variant H3.3 in gene bodies. Here we show that the candidate tumour suppressor ZMYND11 specifically recognizes H3K36me3 on H3.3 (H3.3K36me3) and regulates RNA polymerase II elongation. Structural studies show that in addition to the trimethyl-lysine binding by an aromatic cage within the PWWP domain, the H3.3-dependent recognition is mediated by the encapsulation of the H3.3-specific ‘Ser 31’ residue in a composite pocket formed by the tandem bromo–PWWP domains of ZMYND11. Chromatin immunoprecipitation followed by sequencing shows a genome-wide co-localization of ZMYND11 with H3K36me3 and H3.3 in gene bodies, and its occupancy requires the pre-deposition of H3.3K36me3. Although ZMYND11 is associated with highly expressed genes, it functions as an unconventional transcription co-repressor by modulating RNA polymerase II at the elongation stage. ZMYND11 is critical for the repression of a transcriptional program that is essential for tumour cell growth; low expression levels of ZMYND11 in breast cancer patients correlate with worse prognosis. Consistently, overexpression of ZMYND11 suppresses cancer cell growth in vitro and tumour formation in mice. Together, this study identifies ZMYND11 as an H3.3-specific reader of H3K36me3 that links the histone-variant-mediated transcription elongation control to tumour suppression.","title":"ZMYND11 links histone H3.3K36me3 to transcription elongation and tumour suppression"},{"docid":"18676539","text":"FANCM is a component of the Fanconi anemia (FA) core complex and one FA patient (EUFA867) with biallelic mutations in FANCM has been described. Strikingly, we found that EUFA867 also carries biallelic mutations in FANCA. After correcting the FANCA defect in EUFA867 lymphoblasts, a \"clean\" FA-M cell line was generated. These cells were hypersensitive to mitomycin C, but unlike cells defective in other core complex members, FANCM(-/-) cells were proficient in monoubiquitinating FANCD2 and were sensitive to the topoisomerase inhibitor camptothecin, a feature shared only with the FA subtype D1 and N. In addition, FANCM(-/-) cells were sensitive to UV light. FANCM and a C-terminal deletion mutant rescued the cross-linker sensitivity of FANCM(-/-) cells, whereas a FANCM ATPase mutant did not. Because both mutants restored the formation of FANCD2 foci, we conclude that FANCM functions in an FA core complex-dependent and -independent manner.","title":"Impaired FANCD2 monoubiquitination and hypersensitivity to camptothecin uniquely characterize Fanconi anemia complementation group M."},{"docid":"519974","text":"Mammals detect temperature with specialized neurons in the peripheral nervous system. Four TRPV-class channels have been implicated in sensing heat, and one TRPM-class channel in sensing cold. The combined range of temperatures that activate these channels covers a majority of the relevant physiological spectrum sensed by most mammals, with a significant gap in the noxious cold range. Here, we describe the characterization of ANKTM1, a cold-activated channel with a lower activation temperature compared to the cold and menthol receptor, TRPM8. ANKTM1 is a distant family member of TRP channels with very little amino acid similarity to TRPM8. It is found in a subset of nociceptive sensory neurons where it is coexpressed with TRPV1/VR1 (the capsaicin/heat receptor) but not TRPM8. Consistent with the expression of ANKTM1, we identify noxious cold-sensitive sensory neurons that also respond to capsaicin but not to menthol.","title":"ANKTM1, a TRP-like Channel Expressed in Nociceptive Neurons, Is Activated by Cold Temperatures"},{"docid":"2820454","text":"BACKGROUND Pulmonary hypertension (PH) is associated with restricted physical capacity, limited quality of life, and a poor prognosis because of right heart failure. The present study is the first prospective randomized study to evaluate the effects of exercise and respiratory training in patients with severe symptomatic PH. METHODS AND RESULTS Thirty patients with PH (21 women; mean age, 50+/-13 years; mean pulmonary artery pressure, 50+/-15 mm Hg; mean World Health Organization [WHO] class, 2.9+/-0.5; pulmonary arterial hypertension, n=23; chronic thromboembolic PH, n=7) on stable disease-targeted medication were randomly assigned to a control (n=15) and a primary training (n=15) group. Medication remained unchanged during the study period. Primary end points were the changes from baseline to week 15 in the distance walked in 6 minutes and in scores of the Short Form Health Survey quality-of-life questionnaire. Changes in WHO functional class, Borg scale, and parameters of echocardiography and gas exchange also were assessed. At week 15, patients in the primary and secondary training groups had an improved 6-minute walking distance; the mean difference between the control and the primary training group was 111 m (95% confidence interval, 65 to 139 m; P<0.001). Exercise training was well tolerated and improved scores of quality of life, WHO functional class, peak oxygen consumption, oxygen consumption at the anaerobic threshold, and achieved workload. Systolic pulmonary artery pressure values at rest did not change significantly after 15 weeks of exercise and respiratory training (from 61+/-18 to 54+/-18 mm Hg) within the training group. CONCLUSIONS This study indicates that respiratory and physical training could be a promising adjunct to medical treatment in severe PH. The effects add to the beneficial results of modern medical treatment.","title":"Exercise and respiratory training improve exercise capacity and quality of life in patients with severe chronic pulmonary hypertension."},{"docid":"5760247","text":"Chromosome segregation during mitosis requires assembly of the kinetochore complex at the centromere. Kinetochore assembly depends on specific recognition of the histone variant CENP-A in the centromeric nucleosome by centromere protein C (CENP-C). We have defined the determinants of this recognition mechanism and discovered that CENP-C binds a hydrophobic region in the CENP-A tail and docks onto the acidic patch of histone H2A and H2B. We further found that the more broadly conserved CENP-C motif uses the same mechanism for CENP-A nucleosome recognition. Our findings reveal a conserved mechanism for protein recruitment to centromeres and a histone recognition mode whereby a disordered peptide binds the histone tail through hydrophobic interactions facilitated by nucleosome docking.","title":"A conserved mechanism for centromeric nucleosome recognition by centromere protein CENP-C."},{"docid":"121581019","text":"High-quality indium–tin–oxide (ITO) thin films (200–850 nm) have been grown by pulsed laser deposition (PLD) on glass substrates without a postdeposition annealing treatment. The structural, electrical, and optical properties of these films have been investigated as a function of target composition, substrate deposition temperature, background gas pressure, and film thickness. Films were deposited from various target compositions ranging from 0 to 15 wt % of SnO2 content. The optimum target composition for high conductivity was 5 wt % SnO2+95 wt % In2O3. Films were deposited at substrate temperatures ranging from room temperature to 300 °C in O2 partial pressures ranging from 1 to 100 mTorr. Films were deposited using a KrF excimer laser (248 nm, 30 ns full width at half maximum) at a fluence of 2 J/cm2. For a 150-nm-thick ITO film grown at room temperature in an oxygen pressure of 10 mTorr, the resistivity was 4×10−4 Ω cm and the average transmission in the visible range (400–700 nm) was 85%. For a 170-n...","title":"Electrical, optical, and structural properties of indium-tin-oxide thin films for organic light-emitting devices"},{"docid":"1970884","text":"Viruses that replicate in the cytoplasm cannot access the host nuclear capping machinery. These viruses have evolved viral methyltransferase(s) to methylate N-7 and 2'-O cap of their RNA; alternatively, they \"snatch\" host mRNA cap to form the 5' end of viral RNA. The function of 2'-O methylation of viral RNA cap is to mimic cellular mRNA and to evade host innate immune restriction. A cytoplasmic virus defective in 2'-O methylation is replicative, but its viral RNA lacks 2'-O methylation and is recognized and eliminated by the host immune response. Such a mutant virus could be rationally designed as a live attenuated vaccine. Here, we use Japanese encephalitis virus (JEV), an important mosquito-borne flavivirus, to prove this novel vaccine concept. We show that JEV methyltransferase is responsible for both N-7 and 2'-O cap methylations as well as evasion of host innate immune response. Recombinant virus completely defective in 2'-O methylation was stable in cell culture after being passaged for >30 days. The mutant virus was attenuated in mice, elicited robust humoral and cellular immune responses, and retained the engineered mutation in vivo. A single dose of immunization induced full protection against lethal challenge with JEV strains in mice. Mechanistically, the attenuation phenotype was attributed to the enhanced sensitivity of the mutant virus to the antiviral effects of interferon and IFIT proteins. Collectively, the results demonstrate the feasibility of using 2'-O methylation-defective virus as a vaccine approach; this vaccine approach should be applicable to other flaviviruses and nonflaviviruses that encode their own viral 2'-O methyltransferases.","title":"Rational design of a flavivirus vaccine by abolishing viral RNA 2'-O methylation."},{"docid":"43014661","text":"Xeroderma pigmentosum variant (XPV) patients with mutations in the DNA polymerase eta (pol eta) gene are hypersensitive to sunlight and have greatly increased susceptibility to sunlight-induced skin cancer. Consistent with the ability of Pol eta to efficiently bypass UV light-induced cyclobutane pyrimidine dimers, XPV cells lacking Pol eta have diminished capacity to replicate UV-damaged DNA and are sensitive to UV light-induced killing and mutagenesis. To better understand these and other Pol eta functions, we generated Pol eta-deficient mice. Mice homozygous for a null mutation in pol eta are viable, fertile, and do not show any obvious spontaneous defects during the first year of life. However, fibroblasts derived from these mutant mice are sensitive to killing by exposure to UV light, and all Pol eta-deficient mice develop skin tumors after UV irradiation, in contrast to the wild-type littermate controls that did not develop such tumors. These results and biochemical studies of translesion synthesis by mouse Pol eta indicate that Pol eta-dependent bypass of cyclobutane pyrimidine dimers suppresses UV light-induced skin cancer in mice. Moreover, 37.5% of pol eta heterozygous mice also developed skin cancer during 5 months after a 5-month exposure to UV light, suggesting that humans who are heterozygous for mutations in pol eta may also have an increased risk of skin cancer.","title":"Increased susceptibility to UV-induced skin carcinogenesis in polymerase eta-deficient mice."}],"string":"[\n {\n \"docid\": \"10189634\",\n \"text\": \"CENP-A chromatin forms the foundation for kinetochore assembly. Replication-independent incorporation of CENP-A at centromeres depends on its chaperone HJURP(Scm3), and Mis18 in vertebrates and fission yeast. The recruitment of Mis18 and HJURP(Scm3) to centromeres is cell cycle regulated. Vertebrate Mis18 associates with Mis18BP1(KNL2), which is critical for the recruitment of Mis18 and HJURP(Scm3). We identify two novel fission yeast Mis18-interacting proteins (Eic1 and Eic2), components of the Mis18 complex. Eic1 is essential to maintain Cnp1(CENP-A) at centromeres and is crucial for kinetochore integrity; Eic2 is dispensable. Eic1 also associates with Fta7(CENP-Q/Okp1), Cnl2(Nkp2) and Mal2(CENP-O/Mcm21), components of the constitutive CCAN/Mis6/Ctf19 complex. No Mis18BP1(KNL2) orthologue has been identified in fission yeast, consequently it remains unknown how the key Cnp1(CENP-A) loading factor Mis18 is recruited. Our findings suggest that Eic1 serves a function analogous to that of Mis18BP1(KNL2), thus representing the functional counterpart of Mis18BP1(KNL2) in fission yeast that connects with a module within the CCAN/Mis6/Ctf19 complex to allow the temporally regulated recruitment of the Mis18/Scm3(HJURP) Cnp1(CENP-A) loading factors. The novel interactions identified between CENP-A loading factors and the CCAN/Mis6/Ctf19 complex are likely to also contribute to CENP-A maintenance in other organisms.\",\n \"title\": \"Eic1 links Mis18 with the CCAN/Mis6/Ctf19 complex to promote CENP-A assembly\"\n },\n {\n \"docid\": \"16686383\",\n \"text\": \"The centromeric histone H3 variant (CenH3) is essential for chromosome segregation in eukaryotes. We identify posttranslational modifications of Saccharomyces cerevisiae CenH3, Cse4. Functional characterization of cse4 phosphorylation mutants shows growth and chromosome segregation defects when combined with kinetochore mutants okp1 and ame1. Using a phosphoserine-specific antibody, we show that the association of phosphorylated Cse4 with centromeres increases in response to defective microtubule attachment or reduced cohesion. We determine that evolutionarily conserved Ipl1/Aurora B contributes to phosphorylation of Cse4, as levels of phosphorylated Cse4 are reduced at centromeres in ipl1 strains in vivo, and in vitro assays show phosphorylation of Cse4 by Ipl1. Consistent with these results, we observe that a phosphomimetic cse4-4SD mutant suppresses the temperature-sensitive growth of ipl1-2 and Ipl1 substrate mutants dam1 spc34 and ndc80, which are defective for chromosome biorientation. Furthermore, cell biology approaches using a green fluorescent protein-labeled chromosome show that cse4-4SD suppresses chromosome segregation defects in dam1 spc34 strains. On the basis of these results, we propose that phosphorylation of Cse4 destabilizes defective kinetochores to promote biorientation and ensure faithful chromosome segregation. Taken together, our results provide a detailed analysis, in vivo and in vitro, of Cse4 phosphorylation and its role in promoting faithful chromosome segregation.\",\n \"title\": \"Phosphorylation of centromeric histone H3 variant regulates chromosome segregation in Saccharomyces cerevisiae\"\n },\n {\n \"docid\": \"21425864\",\n \"text\": \"Glycosyl phosphatidylinositols (GPIs) anchor many proteins to the surface of eukaryotic cells and may also serve as sorting signals on proteins and participate in signal transduction. We have isolated a Saccharomyces cerevisiae GPI anchoring mutant, gpi1, using a colony screen for cells blocked in [3H]inositol incorporation into protein. The gpi1 mutant is defective in vitro in the synthesis of N-acetylglucosaminyl phosphatidylinositol, the first intermediate in GPI synthesis, and is also temperature-sensitive for growth. Completion of the first step in GPI assembly is therefore required for growth of the unicellular eukaryote S. cerevisiae. GPI synthesis could therefore be exploited as a target for antifungal or antiparasitic agents.\",\n \"title\": \"A conditionally lethal yeast mutant blocked at the first step in glycosyl phosphatidylinositol anchor synthesis.\"\n },\n {\n \"docid\": \"26117607\",\n \"text\": \"Down syndrome cell adhesion molecule (Dscam) seems likely to play a key role in the \\\"alternative adaptive immunity\\\" that has been reported in invertebrates. Dscam consists of a cytoplasmic tail that is involved in signal transduction and a hypervariable extracellular region that might use a pathogen recognition mechanism similar to that used by the vertebrate antibodies. In our previous paper, we isolated a unique tail-less form of Dscam from Litopenaeus vannamei. In this study, we report the first membrane-bound form of shrimp Dscam: PmDscam was isolated from Penaeus monodon, and it occurred in both membrane-bound and tail-less forms. Phylogenetic analysis showed that while the crustacean Dscams from shrimp and water flea did not share a single subclade, they were distinct from the invertebrate Dscam-like molecules and from the insecta Dscams. In the extracellular region, the variable regions of PmDscam were located in N-terminal Ig2, N-terminal Ig3 and the entire Ig7 domain. The PmDscam extracellular variants and transmembrane domain variants were produced by mutually exclusive alternative splicing events. The cytoplasmic tail variants were produced by exon inclusion/exclusion. Based on the genomic organization of Daphnia Dscam's cytoplasmic tail, we propose a model of how the shrimp Dscam genomic locus might use Type III polyadenylation to generate both the tail-less and membrane-bound forms.\",\n \"title\": \"Penaeus monodon Dscam (PmDscam) has a highly diverse cytoplasmic tail and is the first membrane-bound shrimp Dscam to be reported.\"\n },\n {\n \"docid\": \"17671145\",\n \"text\": \"The androgen receptor (AR) is overexpressed and hyperactivated in human castration-resistant prostate cancer (CRPC). However, the determinants of AR overexpression in CRPC are poorly defined. Here we show that retinoic acid receptor-related orphan receptor γ (ROR-γ) is overexpressed and amplified in metastatic CRPC tumors, and that ROR-γ drives AR expression in the tumors. ROR-γ recruits nuclear receptor coactivator 1 and 3 (NCOA1 and NCOA3, also known as SRC-1 and SRC-3) to an AR-ROR response element (RORE) to stimulate AR gene transcription. ROR-γ antagonists suppress the expression of both AR and its variant AR-V7 in prostate cancer (PCa) cell lines and tumors. ROR-γ antagonists also markedly diminish genome-wide AR binding, H3K27ac abundance and expression of the AR target gene network. Finally, ROR-γ antagonists suppressed tumor growth in multiple AR-expressing, but not AR-negative, xenograft PCa models, and they effectively sensitized CRPC tumors to enzalutamide, without overt toxicity, in mice. Taken together, these results establish ROR-γ as a key player in CRPC by acting upstream of AR and as a potential therapeutic target for advanced PCa.\",\n \"title\": \"ROR-γ drives androgen receptor expression and represents a therapeutic target in castration-resistant prostate cancer\"\n },\n {\n \"docid\": \"4312169\",\n \"text\": \"Glioblastoma multiforme (GBM) is a lethal brain tumour in adults and children. However, DNA copy number and gene expression signatures indicate differences between adult and paediatric cases. To explore the genetic events underlying this distinction, we sequenced the exomes of 48 paediatric GBM samples. Somatic mutations in the H3.3-ATRX-DAXX chromatin remodelling pathway were identified in 44% of tumours (21/48). Recurrent mutations in H3F3A, which encodes the replication-independent histone 3 variant H3.3, were observed in 31% of tumours, and led to amino acid substitutions at two critical positions within the histone tail (K27M, G34R/G34V) involved in key regulatory post-translational modifications. Mutations in ATRX (α-thalassaemia/mental retardation syndrome X-linked) and DAXX (death-domain associated protein), encoding two subunits of a chromatin remodelling complex required for H3.3 incorporation at pericentric heterochromatin and telomeres, were identified in 31% of samples overall, and in 100% of tumours harbouring a G34R or G34V H3.3 mutation. Somatic TP53 mutations were identified in 54% of all cases, and in 86% of samples with H3F3A and/or ATRX mutations. Screening of a large cohort of gliomas of various grades and histologies (n = 784) showed H3F3A mutations to be specific to GBM and highly prevalent in children and young adults. Furthermore, the presence of H3F3A/ATRX-DAXX/TP53 mutations was strongly associated with alternative lengthening of telomeres and specific gene expression profiles. This is, to our knowledge, the first report to highlight recurrent mutations in a regulatory histone in humans, and our data suggest that defects of the chromatin architecture underlie paediatric and young adult GBM pathogenesis.\",\n \"title\": \"Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma\"\n },\n {\n \"docid\": \"13293033\",\n \"text\": \"Down syndrome (DS) is the most frequent cause of human congenital mental retardation. Cognitive deficits in DS result from perturbations of normal cellular processes both during development and in adult tissues, but the mechanisms underlying DS etiology remain poorly understood. To assess the ability of induced pluripotent stem cells (iPSCs) to model DS phenotypes, as a prototypical complex human disease, we generated bona fide DS and wild-type (WT) nonviral iPSCs by episomal reprogramming. DS iPSCs selectively overexpressed chromosome 21 genes, consistent with gene dosage, which was associated with deregulation of thousands of genes throughout the genome. DS and WT iPSCs were neurally converted at >95% efficiency and had remarkably similar lineage potency, differentiation kinetics, proliferation, and axon extension at early time points. However, at later time points DS cultures showed a twofold bias toward glial lineages. Moreover, DS neural cultures were up to two times more sensitive to oxidative stress-induced apoptosis, and this could be prevented by the antioxidant N-acetylcysteine. Our results reveal a striking complexity in the genetic alterations caused by trisomy 21 that are likely to underlie DS developmental phenotypes, and indicate a central role for defective early glial development in establishing developmental defects in DS brains. Furthermore, oxidative stress sensitivity is likely to contribute to the accelerated neurodegeneration seen in DS, and we provide proof of concept for screening corrective therapeutics using DS iPSCs and their derivatives. Nonviral DS iPSCs can therefore model features of complex human disease in vitro and provide a renewable and ethically unencumbered discovery platform.\",\n \"title\": \"Integration-free induced pluripotent stem cells model genetic and neural developmental features of down syndrome etiology.\"\n },\n {\n \"docid\": \"26625002\",\n \"text\": \"The outer membrane channel TolC is a key component of multidrug efflux and type I secretion transporters in Escherichia coli. Mutational inactivation of TolC renders cells highly susceptible to antibiotics and leads to defects in secretion of protein toxins. Despite impairment of various transport functions, no growth defects were reported in cells lacking TolC. Unexpectedly, we found that the loss of TolC notably impairs cell division and growth in minimal glucose medium. The TolC-dependent phenotype was further exacerbated by the loss of ygiB and ygiC genes expressed in the same operon as tolC and their homologues yjfM and yjfC located elsewhere on the chromosome. Our results show that this growth deficiency is caused by depletion of the critical metabolite NAD(+) and high NADH/NAD(+) ratios. The increased amounts of PspA and decreased rates of NADH oxidation in Delta tolC membranes indicated stress on the membrane and dissipation of a proton motive force. We conclude that inactivation of TolC triggers metabolic shutdown in E. coli cells grown in minimal glucose medium. The Delta tolC phenotype is partially rescued by YgiBC and YjfMC, which have parallel functions independent from TolC.\",\n \"title\": \"Metabolic shutdown in Escherichia coli cells lacking the outer membrane channel TolC.\"\n },\n {\n \"docid\": \"24725136\",\n \"text\": \"BACKGROUND The combination of ataxia and hypogonadism was first described more than a century ago, but its genetic basis has remained elusive. METHODS We performed whole-exome sequencing in a patient with ataxia and hypogonadotropic hypogonadism, followed by targeted sequencing of candidate genes in similarly affected patients. Neurologic and reproductive endocrine phenotypes were characterized in detail. The effects of sequence variants and the presence of an epistatic interaction were tested in a zebrafish model. RESULTS Digenic homozygous mutations in RNF216 and OTUD4, which encode a ubiquitin E3 ligase and a deubiquitinase, respectively, were found in three affected siblings in a consanguineous family. Additional screening identified compound heterozygous truncating mutations in RNF216 in an unrelated patient and single heterozygous deleterious mutations in four other patients. Knockdown of rnf216 or otud4 in zebrafish embryos induced defects in the eye, optic tectum, and cerebellum; combinatorial suppression of both genes exacerbated these phenotypes, which were rescued by nonmutant, but not mutant, human RNF216 or OTUD4 messenger RNA. All patients had progressive ataxia and dementia. Neuronal loss was observed in cerebellar pathways and the hippocampus; surviving hippocampal neurons contained ubiquitin-immunoreactive intranuclear inclusions. Defects were detected at the hypothalamic and pituitary levels of the reproductive endocrine axis. CONCLUSIONS The syndrome of hypogonadotropic hypogonadism, ataxia, and dementia can be caused by inactivating mutations in RNF216 or by the combination of mutations in RNF216 and OTUD4. These findings link disordered ubiquitination to neurodegeneration and reproductive dysfunction and highlight the power of whole-exome sequencing in combination with functional studies to unveil genetic interactions that cause disease. (Funded by the National Institutes of Health and others.).\",\n \"title\": \"Ataxia, dementia, and hypogonadotropism caused by disordered ubiquitination.\"\n },\n {\n \"docid\": \"7717468\",\n \"text\": \"Microbial survival in a host is usually dependent on the ability of a pathogen to undergo changes that promote escape from host defense mechanisms. The human-pathogenic fungus Cryptococcus neoformans undergoes phenotypic switching in vivo that promotes persistence in tissue. By microarray and real-time PCR analyses, the allergen 1 gene (ALL1) was found to be downregulated in the hypervirulent mucoid switch variant, both during logarithmic growth and during intracellular growth in macrophages. The ALL1 gene encodes a small cytoplasmic protein that is involved in capsule formation. Growth of an all1Delta gene deletion mutant was normal. Similar to cells of the mucoid switch variant, all1Delta cells produced a larger polysaccharide capsule than cells of the smooth parent and the complemented strain produced, and the enlarged capsule inhibited macrophage phagocytosis. The mutant exhibited a modest defect in capsule induction compared to all of the other variants. In animal models the phenotype of the all1Delta mutant mimicked the hypervirulent phenotype of the mucoid switch variant, which is characterized by decreased host survival and elevated intracranial pressure. Decreased survival is likely the result of both an ineffective cell-mediated immune response and impaired phagocytosis by macrophages. Consequently, we concluded that, unlike loss of most virulence-associated genes, where loss of gene function results in attenuated virulence, loss of the ALL1 gene enhances virulence by altering the host-pathogen interaction and thereby impairing clearance. Our data identified the first cryptococcal gene associated with elevated intracranial pressure and support the hypothesis that an environmental opportunistic pathogen has modified its virulence in vivo by epigenetic downregulation of gene function.\",\n \"title\": \"Loss of allergen 1 confers a hypervirulent phenotype that resembles mucoid switch variants of Cryptococcus neoformans.\"\n },\n {\n \"docid\": \"14471161\",\n \"text\": \"Circadian disruption accelerates cancer progression, whereas circadian reinforcement could halt it. Mice with P03 pancreatic adenocarcinoma (n = 77) were synchronized and fed ad libitum (AL) or with meal timing (MT) from Zeitgeber time (ZT) 2 to ZT6 with normal or fat diet. Tumor gene expression profiling was determined with DNA microarrays at endogenous circadian time (CT) 4 and CT16. Circadian mRNA expression patterns were determined for clock genes Rev-erbalpha, Per2, and Bmal1, cellular stress genes Hspa8 and Cirbp, and cyclin A2 gene Ccna2 in liver and tumor. The 24-hour patterns in telemetered rest-activity and body temperature and plasma corticosterone and insulin-like growth factor-I (IGF-I) were assessed. We showed that MT inhibited cancer growth by approximately 40% as compared with AL (P = 0.011) irrespective of calorie intake. Clock gene transcription remained arrhythmic in tumors irrespective of feeding schedule or diet. Yet, MT upregulated or downregulated the expression of 423 tumor genes, according to CT. Moreover, 36 genes involved in cellular stress, cell cycle, and metabolism were upregulated at one CT and downregulated 12 h apart. MT induced >10-fold circadian expression of Hspa8, Cirbp, and Ccna2 in tumors. Corticosterone or IGF-I patterns played no role in tumor growth inhibition. In contrast, MT consistently doubled the circadian amplitude of body temperature. Peak and trough respectively corresponded to peak expressions of Hspa8 and Cirbp in tumors. The reinforcement of the host circadian timing system with MT induced 24-hour rhythmic expression of critical genes in clock-deficient tumors, which translated into cancer growth inhibition. Targeting circadian clocks represents a novel potential challenge for cancer therapeutics.\",\n \"title\": \"Cancer inhibition through circadian reprogramming of tumor transcriptome with meal timing.\"\n },\n {\n \"docid\": \"29564505\",\n \"text\": \"IMPORTANCE Exacerbations of respiratory symptoms in chronic obstructive pulmonary disease (COPD) have profound and long-lasting adverse effects on patients. OBJECTIVE To test the hypothesis that elevated levels of inflammatory biomarkers in individuals with stable COPD are associated with an increased risk of having exacerbations. DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study examining 61,650 participants with spirometry measurements from the Copenhagen City Heart Study (2001-2003) and the Copenhagen General Population Study (2003-2008). Of these, 6574 had COPD, defined as a ratio between forced expiratory volume in 1 second (FEV1) and forced vital capacity below 0.7. MAIN OUTCOMES AND MEASURES Baseline levels of C-reactive protein (CRP) and fibrinogen and leukocyte count were measured in participants at a time when they were not experiencing symptoms of exacerbations. Exacerbations were recorded and defined as short-course treatment with oral corticosteroids alone or in combination with an antibiotic or as a hospital admission due to COPD. Levels of CRP and fibrinogen and leukocyte count were defined as high or low according to cut points of 3 mg/L, 14 μmol/L, and 9 ×10(9)/L, respectively. RESULTS During follow-up, 3083 exacerbations were recorded (mean, 0.5/participant). In the first year of follow-up, multivariable-adjusted odds ratios for having frequent exacerbations were 1.2 (95% CI, 0.7-2.2; 17 events/1000 person-years) for individuals with 1 high biomarker, 1.7 (95% CI, 0.9-3.2; 32 events/1000 person-years) for individuals with 2 high biomarkers, and 3.7 (95% CI, 1.9-7.4; 81 events/1000 person-years) for individuals with 3 high biomarkers compared with individuals who had no elevated biomarkers (9 events/1000 person-years; trend: P = 2 × 10(-5)). Corresponding hazard ratios using maximum follow-up time were 1.4 (95% CI, 1.1-1.8), 1.6 (95% CI, 1.3-2.2), and 2.5 (95% CI, 1.8-3.4), respectively (trend: P = 1 × 10(-8)). The addition of inflammatory biomarkers to a basic model including age, sex, FEV1 percent predicted, smoking, use of any inhaled medication, body mass index, history of previous exacerbations, and time since most recent prior exacerbation improved the C statistics from 0.71 to 0.73 (comparison: P = 9 × 10(-5)). Relative risks were consistent in those with milder COPD, in those with no history of frequent exacerbations, and in the 2 studies separately. The highest 5-year absolute risks of having frequent exacerbations in those with 3 high biomarkers (vs no high biomarkers) were 62% (vs 24%) for those with Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades C-D (n = 558), 98% (vs 64%) in those with a history of frequent exacerbations (n = 127), and 52% (vs 15%) for those with GOLD grades 3-4 (n = 465). CONCLUSIONS AND RELEVANCE Simultaneously elevated levels of CRP and fibrinogen and leukocyte count in individuals with COPD were associated with increased risk of having exacerbations, even in those with milder COPD and in those without previous exacerbations. Further investigation is needed to determine the clinical value of these biomarkers for risk stratification.\",\n \"title\": \"Inflammatory biomarkers and exacerbations in chronic obstructive pulmonary disease.\"\n },\n {\n \"docid\": \"23117928\",\n \"text\": \"Infection of Sulfolobus islandicus REY15A with mixtures of different Sulfolobus viruses, including STSV2, did not induce spacer acquisition by the host CRISPR immune system. However, coinfection with the tailed fusiform viruses SMV1 and STSV2 generated hyperactive spacer acquisition in both CRISPR loci, exclusively from STSV2, with the resultant loss of STSV2 but not SMV1. SMV1 was shown to activate adaptation while itself being resistant to CRISPR-mediated adaptation and DNA interference. Exceptionally, a single clone S-1 isolated from an SMV1 + STSV2-infected culture, that carried STSV2-specific spacers and had lost STSV2 but not SMV1, acquired spacers from SMV1. This effect was also reproducible on reinfecting wild-type host cells with a variant SMV1 isolated from the S-1 culture. The SMV1 variant lacked a virion protein ORF114 that was shown to bind DNA. This study also provided evidence for: (i) limits on the maximum sizes of CRISPR loci; (ii) spacer uptake strongly retarding growth of infected cultures; (iii) protospacer selection being essentially random and non-directional, and (iv) the reversible uptake of spacers from STSV2 and SMV1. A hypothesis is presented to explain the interactive conflicts between SMV1 and the host CRISPR immune system.\",\n \"title\": \"Inter-viral conflicts that exploit host CRISPR immune systems of Sulfolobus.\"\n },\n {\n \"docid\": \"6766459\",\n \"text\": \"Fever is commonly used to diagnose disease and is consistently associated with increased mortality in critically ill patients. However, the molecular controls of elevated body temperature are poorly understood. We discovered that the expression of RNA-binding motif protein 3 (RBM3), known to respond to cold stress and to modulate microRNA (miRNA) expression, was reduced in 30 patients with fever, and in THP-1-derived macrophages maintained at a fever-like temperature (40 °C). Notably, RBM3 expression is reduced during fever whether or not infection is demonstrable. Reduced RBM3 expression resulted in increased expression of RBM3-targeted temperature-sensitive miRNAs, we termed thermomiRs. ThermomiRs such as miR-142-5p and miR-143 in turn target endogenous pyrogens including IL-6, IL6ST, TLR2, PGE2 and TNF to complete a negative feedback mechanism, which may be crucial to prevent pathological hyperthermia. Using normal PBMCs that were exogenously exposed to fever-like temperature (40 °C), we further demonstrate the trend by which decreased levels of RBM3 were associated with increased levels of miR-142-5p and miR-143 and vice versa over a 24 h time course. Collectively, our results indicate the existence of a negative feedback loop that regulates fever via reduced RBM3 levels and increased expression of miR-142-5p and miR-143.\",\n \"title\": \"RBM3 regulates temperature sensitive miR-142–5p and miR-143 (thermomiRs), which target immune genes and control fever\"\n },\n {\n \"docid\": \"26596106\",\n \"text\": \"In the yeast S. cerevisiae, ribosome assembly is linked to environmental conditions by the coordinate transcriptional regulation of genes required for ribosome biogenesis. In this study we show that two nonessential stress-responsive genes, YAR1 and LTV1, function in 40S subunit production. We provide genetic and biochemical evidence that Yar1, a small ankyrin-repeat protein, physically interacts with RpS3, a component of the 40S subunit, and with Ltv1, a protein recently identified as a substoichiometric component of a 43S preribosomal particle. We demonstrate that cells lacking YAR1 or LTV1 are hypersensitive to particular protein synthesis inhibitors and exhibit aberrant polysome profiles, with a reduced absolute number of 40S subunits and an excess of free 60S subunits. Surprisingly, both mutants are also hypersensitive to a variety of environmental stress conditions. Overexpression of RPS3 suppresses both the stress sensitivity and the ribosome biogenesis defect of Deltayar1 mutants, but does not suppress either defect in Deltaltv1 mutants. We propose that YAR1 and LTV1 play distinct, nonessential roles in 40S subunit production. The stress-sensitive phenotypes of strains lacking these genes reveal a hitherto unknown link between ribosome biogenesis factors and environmental stress sensitivity.\",\n \"title\": \"Genetic and biochemical interactions among Yar1, Ltv1 and Rps3 define novel links between environmental stress and ribosome biogenesis in Saccharomyces cerevisiae.\"\n },\n {\n \"docid\": \"34016944\",\n \"text\": \"PURPOSE Tyrosine kinase (TK) inhibitors are emerging as a promising new approach to the treatment of HER overexpressing tumors, however optimal use of these agents awaits further definition of the downstream signaling pathways that mediate their effects. We reported previously that both EGFR- and Her2-overexpressing tumors are sensitive to the new EGFR-selective TK inhibitor gefitinib (ZD1839, \\\"Iressa\\\"), and sensitivity to this agent correlated with its ability to down-regulate Akt. However, EGFR-overexpressing MDA-468 cells, which lack PTEN function, are resistant to ZD1839, and ZD1839 is unable to down-regulate Akt activity in these cells. EXPERIMENTAL DESIGN To study the role of PTEN function, we generated MDA468 cells with tet-inducible PTEN expression. RESULTS We show here that the resistance of MDA-468 cells to ZD1839 is attributable to EGFR-independent constitutive Akt activation caused by loss of PTEN function in these cells. Reconstitution of PTEN function through tet-inducible expression restores ZD1839 sensitivity to these cells and reestablishes EGFR-stimulated Akt signaling. Although restoration of PTEN function to tumors is difficult to implement clinically, much of the effects of PTEN loss are attributable to overactive PI3K/Akt pathway signaling, and this overactivity can be modulated by pharmacologic approaches. We show here that pharmacologic down-regulation of constitutive PI3K/Akt pathway signaling using the PI3K inhibitor LY294002 similarly restores EGFR-stimulated Akt signaling and sensitizes MDA-468 cells to ZD1839. CONCLUSIONS Sensitivity to ZD1839 requires intact growth factor receptor-stimulated Akt signaling activity. PTEN loss leads to uncoupling of this signaling pathway and results in ZD1839 resistance, which can be reversed with reintroduction of PTEN or pharmacologic down-regulation of constitutive PI3K/Akt pathway activity. These data have important predictive and therapeutic clinical implications.\",\n \"title\": \"Resistance to gefitinib in PTEN-null HER-overexpressing tumor cells can be overcome through restoration of PTEN function or pharmacologic modulation of constitutive phosphatidylinositol 3'-kinase/Akt pathway signaling.\"\n },\n {\n \"docid\": \"22362025\",\n \"text\": \"Small regulatory RNAs are key regulators of gene expression. One class of small regulatory RNAs, termed the endogenous small interfering RNAs (endo siRNAs), is thought to negatively regulate cellular transcripts via an RNA interference (RNAi)-like mechanism termed endogenous RNAi (endo RNAi). A complex of proteins composed of ERI-1/3/5, RRF-3, and DICER (the ERI/DICER complex) mediates endo RNAi processes in Caenorhabditis elegans. We conducted a genetic screen to identify additional components of the endo RNAi machinery. Our screen recovered alleles of eri-9, which encodes a novel DICER-interacting protein, and a missense mutation within the helicase domain of DICER [DCR-1(G492R)]. ERI-9(-) and DCR-1(G492) animals exhibit defects in endo siRNA expression and a concomitant failure to regulate mRNAs that exhibit sequence homology to these endo siRNAs, indicating that ERI-9 and the DCR-1 helicase domain function in the C. elegans endo RNAi pathway. We define a subset of Eri mutant animals (including eri-1, rrf-3, eri-3, and dcr-1, but not eri-9 or ergo-1) that exhibit temperature-sensitive, sperm-specific sterility and defects in X chromosome segregation. Among these mutants we find multiple aberrations in sperm development beginning with cytokinesis and extending through terminal differentiation. These results identify novel components of the endo RNAi machinery, demonstrate differential requirements for the Eri factors in the sperm-producing germline, and begin to delineate the functional requirement for the ERI/DICER complex in sperm development.\",\n \"title\": \"Requirement for the ERI/DICER complex in endogenous RNA interference and sperm development in Caenorhabditis elegans.\"\n },\n {\n \"docid\": \"9315213\",\n \"text\": \"BACKGROUND Fibroblast growth factor 21 (FGF21) is a metabolic hormone with pleiotropic effects on glucose and lipid metabolism and insulin sensitivity. It acts as a key downstream target of both peroxisome proliferator-activated receptor α and γ, the agonists of which have been used for lipid lowering and insulin sensitization, respectively. However, the role of FGF21 in the cardiovascular system remains elusive. METHODS AND RESULTS The roles of FGF21 in atherosclerosis were investigated by evaluating the impact of FGF21 deficiency and replenishment with recombinant FGF21 in apolipoprotein E(-/-) mice. FGF21 deficiency causes a marked exacerbation of atherosclerotic plaque formation and premature death in apolipoprotein E(-/-) mice, which is accompanied by hypoadiponectinemia and severe hypercholesterolemia. Replenishment of FGF21 protects against atherosclerosis in apolipoprotein E(-/-)mice via 2 independent mechanisms, inducing the adipocyte production of adiponectin, which in turn acts on the blood vessels to inhibit neointima formation and macrophage inflammation, and suppressing the hepatic expression of the transcription factor sterol regulatory element-binding protein-2, thereby leading to reduced cholesterol synthesis and attenuation of hypercholesterolemia. Chronic treatment with adiponectin partially reverses atherosclerosis without obvious effects on hypercholesterolemia in FGF21-deficient apolipoprotein E(-/-) mice. By contrast, the cholesterol-lowering effects of FGF21 are abrogated by hepatic expression of sterol regulatory element-binding protein-2. CONCLUSIONS FGF21 protects against atherosclerosis via fine tuning the multiorgan crosstalk among liver, adipose tissue, and blood vessels.\",\n \"title\": \"Fibroblast Growth Factor 21 Prevents Atherosclerosis by Suppression of Hepatic Sterol Regulatory Element-Binding Protein-2 and Induction of Adiponectin in Mice\"\n },\n {\n \"docid\": \"10169908\",\n \"text\": \"PURPOSE We have previously identified solute-linked carrier family A1 member 5 (SLC1A5) as an overexpressed protein in a shotgun proteomic analysis of stage I non-small cell lung cancer (NSCLC) when compared with matched controls. We hypothesized that overexpression of SLC1A5 occurs to meet the metabolic demand for lung cancer cell growth and survival. EXPERIMENTAL DESIGN To test our hypothesis, we first analyzed the protein expression of SLC1A5 in archival lung cancer tissues by immunohistochemistry and immunoblotting (N = 98) and in cell lines (N = 36). To examine SLC1A5 involvement in amino acid transportation, we conducted kinetic analysis of l-glutamine (Gln) uptake in lung cancer cell lines in the presence and absence of a pharmacologic inhibitor of SLC1A5, gamma-l-Glutamyl-p-Nitroanilide (GPNA). Finally, we examined the effect of Gln deprivation and uptake inhibition on cell growth, cell-cycle progression, and growth signaling pathways of five lung cancer cell lines. RESULTS Our results show that (i) SLC1A5 protein is expressed in 95% of squamous cell carcinomas (SCC), 74% of adenocarcinomas (ADC), and 50% of neuroendocrine tumors; (ii) SLC1A5 is located at the cytoplasmic membrane and is significantly associated with SCC histology and male gender; (iii) 68% of Gln is transported in a Na(+)-dependent manner, 50% of which is attributed to SLC1A5 activity; and (iv) pharmacologic and genetic targeting of SLC1A5 decreased cell growth and viability in lung cancer cells, an effect mediated in part by mTOR signaling. CONCLUSIONS These results suggest that SLC1A5 plays a key role in Gln transport controlling lung cancer cells' metabolism, growth, and survival.\",\n \"title\": \"SLC1A5 mediates glutamine transport required for lung cancer cell growth and survival.\"\n },\n {\n \"docid\": \"22522432\",\n \"text\": \"The stable contact of ISW2 with nucleosomal DNA approximately 20 bp from the dyad was shown by DNA footprinting and photoaffinity labeling using recombinant histone octamers to require the histone H4 N-terminal tail. Efficient ISW2 remodeling also required the H4 N-terminal tail, although the lack of the H4 tail can be mostly compensated for by increasing the incubation time or concentration of ISW2. Similarly, the length of extranucleosomal DNA affected the stable contact of ISW2 with this same internal nucleosomal site, with the optimal length being 70 to 85 bp. These data indicate the histone H4 tail, in concert with a favorable length of extranucleosomal DNA, recruits and properly orients ISW2 onto the nucleosome for efficient nucleosome remodeling. One consequence of this property of ISW2 is likely its previously observed nucleosome spacing activity.\",\n \"title\": \"Regulation of ISW2 by concerted action of histone H4 tail and extranucleosomal DNA.\"\n },\n {\n \"docid\": \"12225214\",\n \"text\": \"Ubiquitination controls a broad range of cellular functions. The last step of the ubiquitination pathway is regulated by enzyme type 3 (E3) ubiquitin ligases. E3 enzymes are responsible for substrate specificity and catalyze the formation of an isopeptide bond between a lysine residue of the substrate (or the N terminus of the substrate) and ubiquitin. MIR1 and MIR2 are two E3 ubiquitin ligases encoded by Kaposi's sarcoma-associated herpesvirus that mediate the ubiquitination of major histocompatibility complex class I (MHC I) molecules and subsequent internalization. Here, we found that MIR1, but not MIR2, promoted down-regulation of MHC I molecules lacking lysine residues in their intracytoplasmic domain. In the presence of MIR1, these MHC I molecules were ubiquitinated, and their association with ubiquitin was sensitive to beta2-mercaptoethanol, unlike lysine-ubiquitin bonds. This form of ubiquitination required a cysteine residue in the intracytoplasmic tail of MHC I molecules. An MHC I molecule containing a single cysteine residue in an artificial glycine and alanine intracytoplasmic domain was endocytosed and degraded in the presence of MIR1. Thus, ubiquitination can occur on proteins lacking accessible lysines or an accessible N terminus.\",\n \"title\": \"Ubiquitination on nonlysine residues by a viral E3 ubiquitin ligase.\"\n },\n {\n \"docid\": \"435529\",\n \"text\": \"HEN1-mediated 2'-O-methylation has been shown to be a key mechanism to protect plant microRNAs (miRNAs) and small interfering RNAs (siRNAs) as well as animal piwi-interacting RNAs (piRNAs) from degradation and 3' terminal uridylation [1-8]. However, enzymes uridylating unmethylated miRNAs, siRNAs, or piRNAs in hen1 are unknown. In this study, a genetic screen identified a second-site mutation hen1 suppressor1-2 (heso1-2) that partially suppresses the morphological phenotypes of the hypomorphic hen1-2 allele and the null hen1-1 allele in Arabidopsis. HESO1 encodes a terminal nucleotidyl transferase that prefers to add untemplated uridine to the 3' end of RNA, which is completely abolished by 2'-O-methylation. heso1-2 affects the profile of u-tailed miRNAs and siRNAs and increases the abundance of truncated and/or normal sized ones in hen1, which often results in increased total amount of miRNAs and siRNAs in hen1. In contrast, overexpressing HESO1 in hen1-2 causes more severe morphological defects and less accumulation of miRNAs. These results demonstrate that HESO1 is an enzyme uridylating unmethylated miRNAs and siRNAs in hen1. These observations also suggest that uridylation may destabilize unmethylated miRNAs through an unknown mechanism and compete with 3'-to-5' exoribonuclease activities in hen1. This study shall have implications on piRNA uridylation in hen1 in animals.\",\n \"title\": \"Uridylation of miRNAs by HEN1 SUPPRESSOR1 in Arabidopsis\"\n },\n {\n \"docid\": \"4455466\",\n \"text\": \"Recognition of modified histones by ‘reader’ proteins plays a critical role in the regulation of chromatin. H3K36 trimethylation (H3K36me3) is deposited onto the nucleosomes in the transcribed regions after RNA polymerase II elongation. In yeast, this mark in turn recruits epigenetic regulators to reset the chromatin to a relatively repressive state, thus suppressing cryptic transcription. However, much less is known about the role of H3K36me3 in transcription regulation in mammals. This is further complicated by the transcription-coupled incorporation of the histone variant H3.3 in gene bodies. Here we show that the candidate tumour suppressor ZMYND11 specifically recognizes H3K36me3 on H3.3 (H3.3K36me3) and regulates RNA polymerase II elongation. Structural studies show that in addition to the trimethyl-lysine binding by an aromatic cage within the PWWP domain, the H3.3-dependent recognition is mediated by the encapsulation of the H3.3-specific ‘Ser 31’ residue in a composite pocket formed by the tandem bromo–PWWP domains of ZMYND11. Chromatin immunoprecipitation followed by sequencing shows a genome-wide co-localization of ZMYND11 with H3K36me3 and H3.3 in gene bodies, and its occupancy requires the pre-deposition of H3.3K36me3. Although ZMYND11 is associated with highly expressed genes, it functions as an unconventional transcription co-repressor by modulating RNA polymerase II at the elongation stage. ZMYND11 is critical for the repression of a transcriptional program that is essential for tumour cell growth; low expression levels of ZMYND11 in breast cancer patients correlate with worse prognosis. Consistently, overexpression of ZMYND11 suppresses cancer cell growth in vitro and tumour formation in mice. Together, this study identifies ZMYND11 as an H3.3-specific reader of H3K36me3 that links the histone-variant-mediated transcription elongation control to tumour suppression.\",\n \"title\": \"ZMYND11 links histone H3.3K36me3 to transcription elongation and tumour suppression\"\n },\n {\n \"docid\": \"18676539\",\n \"text\": \"FANCM is a component of the Fanconi anemia (FA) core complex and one FA patient (EUFA867) with biallelic mutations in FANCM has been described. Strikingly, we found that EUFA867 also carries biallelic mutations in FANCA. After correcting the FANCA defect in EUFA867 lymphoblasts, a \\\"clean\\\" FA-M cell line was generated. These cells were hypersensitive to mitomycin C, but unlike cells defective in other core complex members, FANCM(-/-) cells were proficient in monoubiquitinating FANCD2 and were sensitive to the topoisomerase inhibitor camptothecin, a feature shared only with the FA subtype D1 and N. In addition, FANCM(-/-) cells were sensitive to UV light. FANCM and a C-terminal deletion mutant rescued the cross-linker sensitivity of FANCM(-/-) cells, whereas a FANCM ATPase mutant did not. Because both mutants restored the formation of FANCD2 foci, we conclude that FANCM functions in an FA core complex-dependent and -independent manner.\",\n \"title\": \"Impaired FANCD2 monoubiquitination and hypersensitivity to camptothecin uniquely characterize Fanconi anemia complementation group M.\"\n },\n {\n \"docid\": \"519974\",\n \"text\": \"Mammals detect temperature with specialized neurons in the peripheral nervous system. Four TRPV-class channels have been implicated in sensing heat, and one TRPM-class channel in sensing cold. The combined range of temperatures that activate these channels covers a majority of the relevant physiological spectrum sensed by most mammals, with a significant gap in the noxious cold range. Here, we describe the characterization of ANKTM1, a cold-activated channel with a lower activation temperature compared to the cold and menthol receptor, TRPM8. ANKTM1 is a distant family member of TRP channels with very little amino acid similarity to TRPM8. It is found in a subset of nociceptive sensory neurons where it is coexpressed with TRPV1/VR1 (the capsaicin/heat receptor) but not TRPM8. Consistent with the expression of ANKTM1, we identify noxious cold-sensitive sensory neurons that also respond to capsaicin but not to menthol.\",\n \"title\": \"ANKTM1, a TRP-like Channel Expressed in Nociceptive Neurons, Is Activated by Cold Temperatures\"\n },\n {\n \"docid\": \"2820454\",\n \"text\": \"BACKGROUND Pulmonary hypertension (PH) is associated with restricted physical capacity, limited quality of life, and a poor prognosis because of right heart failure. The present study is the first prospective randomized study to evaluate the effects of exercise and respiratory training in patients with severe symptomatic PH. METHODS AND RESULTS Thirty patients with PH (21 women; mean age, 50+/-13 years; mean pulmonary artery pressure, 50+/-15 mm Hg; mean World Health Organization [WHO] class, 2.9+/-0.5; pulmonary arterial hypertension, n=23; chronic thromboembolic PH, n=7) on stable disease-targeted medication were randomly assigned to a control (n=15) and a primary training (n=15) group. Medication remained unchanged during the study period. Primary end points were the changes from baseline to week 15 in the distance walked in 6 minutes and in scores of the Short Form Health Survey quality-of-life questionnaire. Changes in WHO functional class, Borg scale, and parameters of echocardiography and gas exchange also were assessed. At week 15, patients in the primary and secondary training groups had an improved 6-minute walking distance; the mean difference between the control and the primary training group was 111 m (95% confidence interval, 65 to 139 m; P<0.001). Exercise training was well tolerated and improved scores of quality of life, WHO functional class, peak oxygen consumption, oxygen consumption at the anaerobic threshold, and achieved workload. Systolic pulmonary artery pressure values at rest did not change significantly after 15 weeks of exercise and respiratory training (from 61+/-18 to 54+/-18 mm Hg) within the training group. CONCLUSIONS This study indicates that respiratory and physical training could be a promising adjunct to medical treatment in severe PH. The effects add to the beneficial results of modern medical treatment.\",\n \"title\": \"Exercise and respiratory training improve exercise capacity and quality of life in patients with severe chronic pulmonary hypertension.\"\n },\n {\n \"docid\": \"5760247\",\n \"text\": \"Chromosome segregation during mitosis requires assembly of the kinetochore complex at the centromere. Kinetochore assembly depends on specific recognition of the histone variant CENP-A in the centromeric nucleosome by centromere protein C (CENP-C). We have defined the determinants of this recognition mechanism and discovered that CENP-C binds a hydrophobic region in the CENP-A tail and docks onto the acidic patch of histone H2A and H2B. We further found that the more broadly conserved CENP-C motif uses the same mechanism for CENP-A nucleosome recognition. Our findings reveal a conserved mechanism for protein recruitment to centromeres and a histone recognition mode whereby a disordered peptide binds the histone tail through hydrophobic interactions facilitated by nucleosome docking.\",\n \"title\": \"A conserved mechanism for centromeric nucleosome recognition by centromere protein CENP-C.\"\n },\n {\n \"docid\": \"121581019\",\n \"text\": \"High-quality indium–tin–oxide (ITO) thin films (200–850 nm) have been grown by pulsed laser deposition (PLD) on glass substrates without a postdeposition annealing treatment. The structural, electrical, and optical properties of these films have been investigated as a function of target composition, substrate deposition temperature, background gas pressure, and film thickness. Films were deposited from various target compositions ranging from 0 to 15 wt % of SnO2 content. The optimum target composition for high conductivity was 5 wt % SnO2+95 wt % In2O3. Films were deposited at substrate temperatures ranging from room temperature to 300 °C in O2 partial pressures ranging from 1 to 100 mTorr. Films were deposited using a KrF excimer laser (248 nm, 30 ns full width at half maximum) at a fluence of 2 J/cm2. For a 150-nm-thick ITO film grown at room temperature in an oxygen pressure of 10 mTorr, the resistivity was 4×10−4 Ω cm and the average transmission in the visible range (400–700 nm) was 85%. For a 170-n...\",\n \"title\": \"Electrical, optical, and structural properties of indium-tin-oxide thin films for organic light-emitting devices\"\n },\n {\n \"docid\": \"1970884\",\n \"text\": \"Viruses that replicate in the cytoplasm cannot access the host nuclear capping machinery. These viruses have evolved viral methyltransferase(s) to methylate N-7 and 2'-O cap of their RNA; alternatively, they \\\"snatch\\\" host mRNA cap to form the 5' end of viral RNA. The function of 2'-O methylation of viral RNA cap is to mimic cellular mRNA and to evade host innate immune restriction. A cytoplasmic virus defective in 2'-O methylation is replicative, but its viral RNA lacks 2'-O methylation and is recognized and eliminated by the host immune response. Such a mutant virus could be rationally designed as a live attenuated vaccine. Here, we use Japanese encephalitis virus (JEV), an important mosquito-borne flavivirus, to prove this novel vaccine concept. We show that JEV methyltransferase is responsible for both N-7 and 2'-O cap methylations as well as evasion of host innate immune response. Recombinant virus completely defective in 2'-O methylation was stable in cell culture after being passaged for >30 days. The mutant virus was attenuated in mice, elicited robust humoral and cellular immune responses, and retained the engineered mutation in vivo. A single dose of immunization induced full protection against lethal challenge with JEV strains in mice. Mechanistically, the attenuation phenotype was attributed to the enhanced sensitivity of the mutant virus to the antiviral effects of interferon and IFIT proteins. Collectively, the results demonstrate the feasibility of using 2'-O methylation-defective virus as a vaccine approach; this vaccine approach should be applicable to other flaviviruses and nonflaviviruses that encode their own viral 2'-O methyltransferases.\",\n \"title\": \"Rational design of a flavivirus vaccine by abolishing viral RNA 2'-O methylation.\"\n },\n {\n \"docid\": \"43014661\",\n \"text\": \"Xeroderma pigmentosum variant (XPV) patients with mutations in the DNA polymerase eta (pol eta) gene are hypersensitive to sunlight and have greatly increased susceptibility to sunlight-induced skin cancer. Consistent with the ability of Pol eta to efficiently bypass UV light-induced cyclobutane pyrimidine dimers, XPV cells lacking Pol eta have diminished capacity to replicate UV-damaged DNA and are sensitive to UV light-induced killing and mutagenesis. To better understand these and other Pol eta functions, we generated Pol eta-deficient mice. Mice homozygous for a null mutation in pol eta are viable, fertile, and do not show any obvious spontaneous defects during the first year of life. However, fibroblasts derived from these mutant mice are sensitive to killing by exposure to UV light, and all Pol eta-deficient mice develop skin tumors after UV irradiation, in contrast to the wild-type littermate controls that did not develop such tumors. These results and biochemical studies of translesion synthesis by mouse Pol eta indicate that Pol eta-dependent bypass of cyclobutane pyrimidine dimers suppresses UV light-induced skin cancer in mice. Moreover, 37.5% of pol eta heterozygous mice also developed skin cancer during 5 months after a 5-month exposure to UV light, suggesting that humans who are heterozygous for mutations in pol eta may also have an increased risk of skin cancer.\",\n \"title\": \"Increased susceptibility to UV-induced skin carcinogenesis in polymerase eta-deficient mice.\"\n }\n]"}}},{"rowIdx":182,"cells":{"query_id":{"kind":"string","value":"5abf7dd75542994516f454b4"},"query":{"kind":"string","value":"What continent is the home of both Alternanthera and Platycodon species?"},"positive_passages":{"kind":"list like","value":[{"docid":"937482","text":"Alternanthera is a genus of flowering plants in the amaranth family, Amaranthaceae. It is a widespread genus with most species occurring in the tropical Americas, and others in Asia, Africa, and Australia. Plants of the genus may be known generally as joyweeds, or Joseph's coat. Several species are notorious noxious weeds.","title":""},{"docid":"2180238","text":"Platycodon grandiflorus (from Ancient Greek πλατύς \"wide\" and κώδων \"bell\") is a species of herbaceous flowering perennial plant of the family Campanulaceae, and the only member of the genus Platycodon. It is native to East Asia (China, Korea, Japan, and the Russian Far East). It is commonly known as balloon flower (referring to the balloon-shaped flower buds), Chinese bellflower, or platycodon.","title":""}],"string":"[\n {\n \"docid\": \"937482\",\n \"text\": \"Alternanthera is a genus of flowering plants in the amaranth family, Amaranthaceae. It is a widespread genus with most species occurring in the tropical Americas, and others in Asia, Africa, and Australia. Plants of the genus may be known generally as joyweeds, or Joseph's coat. Several species are notorious noxious weeds.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"2180238\",\n \"text\": \"Platycodon grandiflorus (from Ancient Greek πλατύς \\\"wide\\\" and κώδων \\\"bell\\\") is a species of herbaceous flowering perennial plant of the family Campanulaceae, and the only member of the genus Platycodon. It is native to East Asia (China, Korea, Japan, and the Russian Far East). It is commonly known as balloon flower (referring to the balloon-shaped flower buds), Chinese bellflower, or platycodon.\",\n \"title\": \"\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"12854725","text":"Alternanthera flavicoma is a species of plant in the Amaranthaceae family. It is endemic to Ecuador.","title":""},{"docid":"12854732","text":"Alternanthera galapagensis is a species of plant in the Amaranthaceae family. It is endemic to Ecuador.","title":""},{"docid":"12854755","text":"Alternanthera snodgrassii is a species of plant in the Amaranthaceae family. It is endemic to Ecuador.","title":""},{"docid":"47045917","text":"Alternanthera echinocephala, known as spiny-headed chaff flower, is a shrubby plant in the amaranth family (Amaranthaceae) native to the Galápagos Islands, mainland Ecuador, and Peru. Its relatively large spiny \"heads\" of flowers distinguish it from other species of \"Alternanthera\" found in the Galápagos.","title":""},{"docid":"11540265","text":"Alternanthera littoralis is an African species in the botanical family Amaranthaceae. The leaves are eaten as a vegetable.","title":""},{"docid":"12854721","text":"Alternanthera filifolia is a species of flowering plant in the amaranth family, Amaranthaceae. It is native to the Galápagos Islands.","title":""},{"docid":"12854746","text":"Alternanthera nesiotes is a species of flowering plant in the family Amaranthaceae. It is endemic to the Galápagos Islands, where it is limited to Floreana Island. There are five subpopulations which are susceptible to habitat degradation due to invasive species of plants and animals.","title":""},{"docid":"7064435","text":"Alternanthera reineckii is a species of aquatic plant in the amaranth family, Amaranthaceae. Several cultivars are used as ornamental plants in aquaria.","title":""},{"docid":"12854709","text":"Alternanthera areschougii is a species of plant in the Amaranthaceae family. It is endemic to Ecuador. Its natural habitats are subtropical or tropical dry forests and subtropical or tropical dry shrubland. It is threatened by habitat loss.","title":""},{"docid":"1118925","text":"Alternanthera philoxeroides, commonly referred to as alligator weed, is a native species to the temperate regions of South America, which includes Argentina, Brazil, Paraguay and Uruguay. Argentina alone, hosts around 27 species that fall within the range of the genus Alternanthera. Its geographic range once used to cover only the Parana River region of South America, but it has since expanded to cover over 30 countries, such as the United States, New Zealand, China and many more. This invasive species is believed to have been accidentally introduced to these non-native regions through sediments trapped/attached to tanks and cargo of ships travelling from South America to these various areas.","title":""},{"docid":"12854716","text":"Alternanthera corymbiformis is a species of plant in the Amaranthaceae family. It is endemic to Ecuador. Its natural habitats are subtropical or tropical moist montane forests and subtropical or tropical dry shrubland. It is threatened by habitat loss.","title":""},{"docid":"12854738","text":"Alternanthera grandis is a species of plant in the Amaranthaceae family. It is endemic to Ecuador. Its natural habitats are subtropical or tropical dry forests, subtropical or tropical dry shrubland, and subtropical or tropical high-altitude grassland. It is threatened by habitat loss. This plant is known for its connection to the Memphis Grizzlies. The players on this team all have an insignia of Alternanthera grandis on their shorts during every away game. The species name, Grandis, refers to the Spanish word for large. This plant can be found throughout northern Ecuador and, most notably, in the Basilica of Nuestra Señora de la Merced. The plant is found near the Ark of the Holy Emblem.","title":""},{"docid":"12854743","text":"Alternanthera helleri is a species of plant in the Amaranthaceae family. It is endemic to Ecuador. It is believed to be green in color anywhere from 90 to 100% of the year depending on altitude. The leaves are considered to be highly toxic to humans and should not be consumed under any circumstances.","title":""},{"docid":"14611595","text":"Alternanthera pungens Kunth is a creeping, prostrate perennial pioneer plant of the Amaranthaceae family, spreading by seed and vegetatively, with roots often developing at the nodes of spreading stems. A plant of roadsides, path verges and waste places (ruderal), it is thought to have come from Central and South America, and to have become widely established in Australia and Southern Africa. Other species of this genus, e.g. \"Alternanthera sessilis\" (L.) R.Br. ex DC., have long been recorded from Tropical Africa, and would be difficult to prove as invaders.","title":""},{"docid":"25671333","text":"Alternanthera bettzickiana (syn. \"A. amoena\") is a species of flowering plant in the amaranth family, Amaranthaceae. It is commonly used as an ornamental edging plant. It is particularly popular in China, where it is \"cultivated in nearly all the large cities\". It is native to South America. Its common names include calico-plant.","title":""},{"docid":"48166751","text":"The North American Continent is home to a wide variety of carnivorous plant species. Species from seven genera are native to the continent, and three of these genera are found nowhere else on the planet.","title":""},{"docid":"48886105","text":"Alternanthera ficoidea is a type of herb belonging to the Amarathaceae family. It is also known as \"Alternanthera tenella,\" and is common and widespread throughout the tropics. It is in fact an endemic herb in the Western Ghats of India. However it is invasive to the island of Palau, and Philippines. The herb has been introduced to Japan, and many other Pacific islands, where they are not invasive. Propagation occurs via seeds.","title":""},{"docid":"9649914","text":"Alternanthera sessilis is an aquatic plant known by several common names, including ponnanganni (in Tamil), ponnaganti aaku (in Telugu),","title":""},{"docid":"21006160","text":"Alternanthera mosaic virus (AltMV) is a plant pathogenic virus. AltMV belongs to the virus genus \"Potexvirus\" and the virus family \"Alphaflexiviridae\".","title":""},{"docid":"852063","text":"The family Campanulaceae (also bellflower family), of the order Asterales, contains nearly 2400 species in 84 genera of herbaceous plants, shrubs, and rarely small trees, often with milky non-toxic sap. Among them are the familiar garden plants \"Campanula\" (bellflower), \"Lobelia\", and \"Platycodon\" (balloonflower).","title":""},{"docid":"53092133","text":"People who choose to run a marathon on all seven continents are generally considered to be a part of the 7 continents club. However, there is some dispute over what counts for each continent, with specific issue being taken due to races being run in \"Antarctica\" that actually take place on outlying islands of the continent and not within the continent itself.","title":""},{"docid":"19885253","text":"Sissoo spinach, also known as Brazilian spinach, Sambu or Samba lettuce, is a tropical edible groundcover of the genus \"Alternanthera\" used as a leaf vegetable. Although it is referred to scientifically as Alternanthera sissoo , there are no known scientific descriptions of its taxonomy.","title":""},{"docid":"689","text":"Asia ( ) is Earth's largest and most populous continent, located primarily in the Eastern and Northern Hemispheres. It shares the continental landmass of Eurasia with the continent of Europe and the continental landmass of Afro-Eurasia with both Europe and Africa. Asia covers an area of 44,579,000 km2 , about 30% of Earth's total land area and 8.7% of the Earth's total surface area. The continent, which has long been home to the majority of the human population, was the site of many of the first civilizations. Asia is notable for not only its overall large size and population, but also dense and large settlements as well as vast barely populated regions within the continent of /1e9 round 1 billion people, or roughly 60% of the world's population.","title":""},{"docid":"15478054","text":"Amynothrips andersoni is a species of thrips known as alligator weed thrips. It has been used as an agent of biological pest control against the noxious aquatic plant known as alligator weed (\"Alternanthera philoxeroides\").","title":""},{"docid":"51067860","text":"Gualicho (named in reference to the gualichu) is a genus of theropod dinosaur. The type species is Gualicho shinyae. \"Gualicho\" lived in what is now northern Patagonia, on what was then a South American island continent split off from the supercontinent Gondwana. The fossils were found in the Huincul Formation, dating to the late Cenomanian-early Turonian age of the upper Cretaceous Period, around 93 million years ago.","title":""},{"docid":"35538251","text":"The Biceratopsinae is an extinct subfamily of trilobites, fossil marine arthropods, with species of small to average size. Species belonging to this subfamily lived during the Toyonian stage (Upper \"Olenellus\"-zone), 516-513 million years ago, in the former continent of Laurentia, including what are today the South-Western United States and Canada.","title":""},{"docid":"36184564","text":"Biceratopsidae is an extinct family of redlichiid trilobites, with species of small to average size. Species of belonging to this family lived during the Toyonian stage (\"Olenellus\"-zone), 522–513 million years ago, in the former continent of Laurentia, including what are today the south-western United States and Canada. It contains the subfamilies Biceratopsinae and Bristoliinae.","title":""},{"docid":"15478247","text":"Arcola malloi (formerly \"Vogtia malloi\") is a species of snout moth known as the alligator weed stem borer. It is used as an agent of biological pest control against the noxious aquatic plant known as alligator weed (\"Alternanthera philoxeroides\").","title":""},{"docid":"1460408","text":"Cyperus is a large genus of about 700 species of sedges, distributed throughout all continents in both tropical and temperate regions.","title":""},{"docid":"1935780","text":"The Birmingham Zoo is a zoological park that opened in 1955 in Birmingham, Alabama (USA). The 122 acre zoo is home to almost 800 animals representing over 200 species, including many endangered species from six continents.","title":""}],"string":"[\n {\n \"docid\": \"12854725\",\n \"text\": \"Alternanthera flavicoma is a species of plant in the Amaranthaceae family. It is endemic to Ecuador.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"12854732\",\n \"text\": \"Alternanthera galapagensis is a species of plant in the Amaranthaceae family. It is endemic to Ecuador.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"12854755\",\n \"text\": \"Alternanthera snodgrassii is a species of plant in the Amaranthaceae family. It is endemic to Ecuador.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"47045917\",\n \"text\": \"Alternanthera echinocephala, known as spiny-headed chaff flower, is a shrubby plant in the amaranth family (Amaranthaceae) native to the Galápagos Islands, mainland Ecuador, and Peru. Its relatively large spiny \\\"heads\\\" of flowers distinguish it from other species of \\\"Alternanthera\\\" found in the Galápagos.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"11540265\",\n \"text\": \"Alternanthera littoralis is an African species in the botanical family Amaranthaceae. The leaves are eaten as a vegetable.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"12854721\",\n \"text\": \"Alternanthera filifolia is a species of flowering plant in the amaranth family, Amaranthaceae. It is native to the Galápagos Islands.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"12854746\",\n \"text\": \"Alternanthera nesiotes is a species of flowering plant in the family Amaranthaceae. It is endemic to the Galápagos Islands, where it is limited to Floreana Island. There are five subpopulations which are susceptible to habitat degradation due to invasive species of plants and animals.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"7064435\",\n \"text\": \"Alternanthera reineckii is a species of aquatic plant in the amaranth family, Amaranthaceae. Several cultivars are used as ornamental plants in aquaria.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"12854709\",\n \"text\": \"Alternanthera areschougii is a species of plant in the Amaranthaceae family. It is endemic to Ecuador. Its natural habitats are subtropical or tropical dry forests and subtropical or tropical dry shrubland. It is threatened by habitat loss.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"1118925\",\n \"text\": \"Alternanthera philoxeroides, commonly referred to as alligator weed, is a native species to the temperate regions of South America, which includes Argentina, Brazil, Paraguay and Uruguay. Argentina alone, hosts around 27 species that fall within the range of the genus Alternanthera. Its geographic range once used to cover only the Parana River region of South America, but it has since expanded to cover over 30 countries, such as the United States, New Zealand, China and many more. This invasive species is believed to have been accidentally introduced to these non-native regions through sediments trapped/attached to tanks and cargo of ships travelling from South America to these various areas.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"12854716\",\n \"text\": \"Alternanthera corymbiformis is a species of plant in the Amaranthaceae family. It is endemic to Ecuador. Its natural habitats are subtropical or tropical moist montane forests and subtropical or tropical dry shrubland. It is threatened by habitat loss.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"12854738\",\n \"text\": \"Alternanthera grandis is a species of plant in the Amaranthaceae family. It is endemic to Ecuador. Its natural habitats are subtropical or tropical dry forests, subtropical or tropical dry shrubland, and subtropical or tropical high-altitude grassland. It is threatened by habitat loss. This plant is known for its connection to the Memphis Grizzlies. The players on this team all have an insignia of Alternanthera grandis on their shorts during every away game. The species name, Grandis, refers to the Spanish word for large. This plant can be found throughout northern Ecuador and, most notably, in the Basilica of Nuestra Señora de la Merced. The plant is found near the Ark of the Holy Emblem.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"12854743\",\n \"text\": \"Alternanthera helleri is a species of plant in the Amaranthaceae family. It is endemic to Ecuador. It is believed to be green in color anywhere from 90 to 100% of the year depending on altitude. The leaves are considered to be highly toxic to humans and should not be consumed under any circumstances.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"14611595\",\n \"text\": \"Alternanthera pungens Kunth is a creeping, prostrate perennial pioneer plant of the Amaranthaceae family, spreading by seed and vegetatively, with roots often developing at the nodes of spreading stems. A plant of roadsides, path verges and waste places (ruderal), it is thought to have come from Central and South America, and to have become widely established in Australia and Southern Africa. Other species of this genus, e.g. \\\"Alternanthera sessilis\\\" (L.) R.Br. ex DC., have long been recorded from Tropical Africa, and would be difficult to prove as invaders.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"25671333\",\n \"text\": \"Alternanthera bettzickiana (syn. \\\"A. amoena\\\") is a species of flowering plant in the amaranth family, Amaranthaceae. It is commonly used as an ornamental edging plant. It is particularly popular in China, where it is \\\"cultivated in nearly all the large cities\\\". It is native to South America. Its common names include calico-plant.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"48166751\",\n \"text\": \"The North American Continent is home to a wide variety of carnivorous plant species. Species from seven genera are native to the continent, and three of these genera are found nowhere else on the planet.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"48886105\",\n \"text\": \"Alternanthera ficoidea is a type of herb belonging to the Amarathaceae family. It is also known as \\\"Alternanthera tenella,\\\" and is common and widespread throughout the tropics. It is in fact an endemic herb in the Western Ghats of India. However it is invasive to the island of Palau, and Philippines. The herb has been introduced to Japan, and many other Pacific islands, where they are not invasive. Propagation occurs via seeds.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"9649914\",\n \"text\": \"Alternanthera sessilis is an aquatic plant known by several common names, including ponnanganni (in Tamil), ponnaganti aaku (in Telugu),\",\n \"title\": \"\"\n },\n {\n \"docid\": \"21006160\",\n \"text\": \"Alternanthera mosaic virus (AltMV) is a plant pathogenic virus. AltMV belongs to the virus genus \\\"Potexvirus\\\" and the virus family \\\"Alphaflexiviridae\\\".\",\n \"title\": \"\"\n },\n {\n \"docid\": \"852063\",\n \"text\": \"The family Campanulaceae (also bellflower family), of the order Asterales, contains nearly 2400 species in 84 genera of herbaceous plants, shrubs, and rarely small trees, often with milky non-toxic sap. Among them are the familiar garden plants \\\"Campanula\\\" (bellflower), \\\"Lobelia\\\", and \\\"Platycodon\\\" (balloonflower).\",\n \"title\": \"\"\n },\n {\n \"docid\": \"53092133\",\n \"text\": \"People who choose to run a marathon on all seven continents are generally considered to be a part of the 7 continents club. However, there is some dispute over what counts for each continent, with specific issue being taken due to races being run in \\\"Antarctica\\\" that actually take place on outlying islands of the continent and not within the continent itself.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"19885253\",\n \"text\": \"Sissoo spinach, also known as Brazilian spinach, Sambu or Samba lettuce, is a tropical edible groundcover of the genus \\\"Alternanthera\\\" used as a leaf vegetable. Although it is referred to scientifically as Alternanthera sissoo , there are no known scientific descriptions of its taxonomy.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"689\",\n \"text\": \"Asia ( ) is Earth's largest and most populous continent, located primarily in the Eastern and Northern Hemispheres. It shares the continental landmass of Eurasia with the continent of Europe and the continental landmass of Afro-Eurasia with both Europe and Africa. Asia covers an area of 44,579,000 km2 , about 30% of Earth's total land area and 8.7% of the Earth's total surface area. The continent, which has long been home to the majority of the human population, was the site of many of the first civilizations. Asia is notable for not only its overall large size and population, but also dense and large settlements as well as vast barely populated regions within the continent of /1e9 round 1 billion people, or roughly 60% of the world's population.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"15478054\",\n \"text\": \"Amynothrips andersoni is a species of thrips known as alligator weed thrips. It has been used as an agent of biological pest control against the noxious aquatic plant known as alligator weed (\\\"Alternanthera philoxeroides\\\").\",\n \"title\": \"\"\n },\n {\n \"docid\": \"51067860\",\n \"text\": \"Gualicho (named in reference to the gualichu) is a genus of theropod dinosaur. The type species is Gualicho shinyae. \\\"Gualicho\\\" lived in what is now northern Patagonia, on what was then a South American island continent split off from the supercontinent Gondwana. The fossils were found in the Huincul Formation, dating to the late Cenomanian-early Turonian age of the upper Cretaceous Period, around 93 million years ago.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"35538251\",\n \"text\": \"The Biceratopsinae is an extinct subfamily of trilobites, fossil marine arthropods, with species of small to average size. Species belonging to this subfamily lived during the Toyonian stage (Upper \\\"Olenellus\\\"-zone), 516-513 million years ago, in the former continent of Laurentia, including what are today the South-Western United States and Canada.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"36184564\",\n \"text\": \"Biceratopsidae is an extinct family of redlichiid trilobites, with species of small to average size. Species of belonging to this family lived during the Toyonian stage (\\\"Olenellus\\\"-zone), 522–513 million years ago, in the former continent of Laurentia, including what are today the south-western United States and Canada. It contains the subfamilies Biceratopsinae and Bristoliinae.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"15478247\",\n \"text\": \"Arcola malloi (formerly \\\"Vogtia malloi\\\") is a species of snout moth known as the alligator weed stem borer. It is used as an agent of biological pest control against the noxious aquatic plant known as alligator weed (\\\"Alternanthera philoxeroides\\\").\",\n \"title\": \"\"\n },\n {\n \"docid\": \"1460408\",\n \"text\": \"Cyperus is a large genus of about 700 species of sedges, distributed throughout all continents in both tropical and temperate regions.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"1935780\",\n \"text\": \"The Birmingham Zoo is a zoological park that opened in 1955 in Birmingham, Alabama (USA). The 122 acre zoo is home to almost 800 animals representing over 200 species, including many endangered species from six continents.\",\n \"title\": \"\"\n }\n]"}}},{"rowIdx":183,"cells":{"query_id":{"kind":"string","value":"PLAIN-1946"},"query":{"kind":"string","value":"protein"},"positive_passages":{"kind":"list like","value":[{"docid":"MED-3302","text":"In November 2007 a novel neuropathy, immune-mediated polyradiculoneuropathy (IP), was identified among workers at a Minnesota swine abattoir where a unique compressed air technique was used to remove porcine brains. An epidemiologic investigation at another abattoir in Indiana that also uses this process was launched to evaluate workers self-reporting neurologic illness compatible with IP. A nested case-control study was performed to identify cases and risk factors. Six confirmed, one probable, and three possible IP cases were detected. IP cases were 28-52 years old, of Latino origin, and 62.5% female. Onset dates ranged from April 2005-December 2007; 60% were hospitalized. IP cases at this plant were similar in clinical presentation and exposure risks to those detected in Minnesota. Swine abattoirs using similar brain extraction methods should discontinue this process.","title":"A clustering of immune-mediated polyradiculoneuropathy among swine abattoir workers exposed to aerosolized porcine brains, Indiana, United States."},{"docid":"MED-2644","text":"Alkylphenols are widely used as plastic additives and surfactants. We report the identification of an alkylphenol, nonylphenol, as an estrogenic substance released from plastic centrifuge tubes. This compound was extracted with methanol, purified by flash chromatography and reverse-phase high performance liquid chromatography, and identified by gas chromatography-mass spectrometry. Nonylphenol induced both cell proliferation and progesterone receptor in human estrogen-sensitive MCF7 breast tumor cells. Nonylphenol also triggered mitotic activity in rat endometrium; this result confirms the reliability of the MCF7 cell proliferation bioassay. The estrogenic properties of alkylphenols, specifically nonylphenols, indicate that the use of plasticware containing these chemicals in experimental and diagnostic tests may lead to spurious results, and these compounds as well as alkylphenol polyethoxylates may also be potentially harmful to exposed humans and the environment at large.","title":"p-Nonyl-phenol: an estrogenic xenobiotic released from \"modified\" polystyrene."},{"docid":"MED-2210","text":"We investigated the effects of sporamin, the major soluble protein with a kunitz-type trypsin inhibitory activity in the root tuber of the sweet potato, on cell proliferation, apoptosis, Akt/GSK-3 signaling and its related genes to provide more insights in the mechanism behind the inhibitory effects of sporamin in a human tongue cancer line Tca8113. In this study, sporamin inhibited cell proliferation and induced apoptosis in Tca8113 cells in a concentration-dependent and time-dependent manner. Consistently, Bax was up-regulated and Bcl-2 was down-regulated in sporamin-treated cells. Furthermore, Akt/GSK-3 signaling was down-regulated in sporamin-treated cells. Consistently, the phosphorylated Bad was significantly declined in sporamin-treated Tca8113 cells. These results suggest the antiproliferative effects of sporamin in Tca8113 cells might result partly from induction of apoptosis by down-regulating Akt/GSK-3 pathway. © 2010 The Authors Fundamental and Clinical Pharmacology © 2010 Société Française de Pharmacologie et de Thérapeutique.","title":"Sporamin induce apoptosis in human tongue carcinoma cells by down-regulating Akt/GSK-3 signaling."},{"docid":"MED-2652","text":"The exposure to some chemicals can lead to hormone disrupting effects. Presently, much attention is focused on so-called xeno-estrogens, synthetic compounds that interact with hormone receptors causing a number of reactions that eventually lead to effects related to reproduction and development. The current study was initiated to investigate the presence of a number of such compounds in precipitation as a follow-up on a previous study in which pesticide concentrations in air and precipitation were determined. Rainwater samples were collected at about 50 locations in The Netherlands in a four week period. The samples were analysed for bisphenol-A, alkylphenols and alkylphenol ethoxylates, phthalates, flame retardants and synthetic musk compounds. The results clearly indicated the presence of these compounds in precipitation. The concentrations ranged from the low ng l(-1) range for flame retardants to several thousands of ng l(-1) for the phthalates. Bisphenol-A was found in 30% of the samples in concentrations up to 130 ng l(-1), while alkylphenols and alkylphenol ethoxylates were found in virtually all locations in concentrations up to 920 ng l(-1) for the individual compounds. Phthalates were by far the most abundant xeno-estrogens in the precipitation samples and were found in every sample. Di-isodecyl phthalate was found in a surprisingly high concentration of almost 100 000 ng l(-1). Polybrominated flame retardants were found in the low ng l(-1) range and generally in less than 20% of the samples. Noticeable was the finding of hexabromocyclododecane, a replacement for the polybrominted diphenyl ethers at one location in a concentration of almost 2000 ng l(-1). Finally, as expected, synthetic musk compounds were detected in almost all samples. This is especially true for the polycyclic musks HHCB and AHTN. Nitro musks were found, but only on a few locations. Kriging techniques were used to calculate precipitation concentrations in between actual sampling locations to produce contour plots for a number of compounds. These plots clearly show located emission sources for a number of compounds such as bisphenol-A, nonylphenol ethoxylate, phthalates and AHTN. On the contrary, the results for HHCB and some phthalates indicated diffuse emission patterns, probably as the result of the use of consumer products containing these compounds.","title":"Xeno-estrogenic compounds in precipitation."},{"docid":"MED-4954","text":"BACKGROUND To look at possible long-term risks from anabolic steroids and other xenobiotics in beef, we examined men's semen quality in relation to their mother's self-reported beef consumption during pregnancy. METHODS: The study was carried out in five US cities between 1999 and 2005. We used regression analyses to examine semen parameters in 387 partners of pregnant women in relation to the amount of beef their mothers reported eating while pregnant. Mothers' beef consumption was also analysed in relation to the son's history of previous subfertility. RESULTS Sperm concentration was inversely related to mothers' beef meals per week (P = 0.041). In sons of \"high beef consumers\" (>7 beef meals/week), sperm concentration was 24.3% lower (P = 0.014) and the proportion of men with sperm concentration below 20 x 10(6)/ml was three times higher (17.7 versus 5.7%, P = 0.002) than in men whose mothers ate less beef. A history of previous subfertility was also more frequent among sons of \"high beef consumers\" (P = 0.015). Sperm concentration was not significantly related to mother's consumption of other meat or to the man's consumption of any meat. CONCLUSIONS These data suggest that maternal beef consumption, and possibly xenobiotics in beef, may alter a man's testicular development in utero and adversely affect his reproductive capacity.","title":"Semen quality of fertile US males in relation to their mothers' beef consumption during pregnancy."},{"docid":"MED-1253","text":"OBJECTIVES: To investigate the effect of replacing lean meat with a soy product, tofu, on serum lipoprotein concentrations. STUDY AND DESIGN: Randomized cross-over dietary intervention study. SUBJECTS: Forty-two free-living healthy males aged 35-62 y completed the dietary intervention. Three additional subjects were non-compliant and excluded prior to analysis. INTERVENTIONS: A diet containing lean meat (150 g/d) was compared with one with 290 g/d tofu in an isocaloric and isoprotein substitution. Both diet periods were 1 month, and fat intake was carefully controlled. RESULTS: Seven-day diet records showed the two diets were similar in energy, macronutrients and fibre. Total cholesterol (mean difference 0.23 mmol/l, 95% CI 0.02, 0.43; P=0.03) and triglycerides (mean difference 0.15 mmol/l, 95% CI 0.02, 0.31; P=0.017) were significantly lower on the tofu diet than the lean meat diet. However, HDL-C was also significantly lower on the tofu diet (mean difference 0.08 mmol/l, 95% CI 0.02, 0.14; P=0.01) although the LDL-C:HDL-C ratio was similar. CONCLUSION: The effect on HDL-C and the small LDL-C reduction differ from some other studies, where fat was often less controlled, and the comparison was of soy as textured protein or soymilk against casein. This suggests a differential effect of the various proteins compared to the soy may influence the findings. In practice, the replacement of meat with tofu would usually be associated with a decrease in saturated fat and an increase in polyunsaturated fat and this should enhance any small benefits due to the soy protein. SPONSOR: Deakin University with some contribution from a Commonwealth Department of Veterans Affairs research grant. European Journal of Clinical Nutrition (2000) 54, 14-19","title":"Effects of soy as tofu vs meat on lipoprotein concentrations."},{"docid":"MED-3784","text":"Dietary choline and betaine have been hypothesized to decrease the risk of cancer because of their role as methyl donors in the one-carbon metabolism. However, it remains unknown whether dietary intake of choline and betaine is associated with colorectal cancer risk. We prospectively examined the associations between dietary choline and betaine intake and risk of colorectal cancer in men in the Health Professionals Follow-up Study. We followed 47,302 men and identified a total of 987 incident colorectal cancer cases from 1986 to 2004. We assessed dietary and supplemental choline and betaine intake every four years using a validated semi-quantitative food frequency questionnaire. The Cox proportional hazards model was used to estimate multivariate relative risks (RRs) and 95% confidence intervals (95% CIs). All statistical tests were two-sided. We did not find any statistically significant associations between choline intake or betaine intake and risk of colorectal cancer. Comparing the top quintile with bottom quintile, multivariate RRs (95% CI) were 0.97 (0.79-1.20; Ptrend = 0.87) for choline intake and 0.94 (0.77-1.16; Ptrend = 0.79) for betaine intake. Similarly, we observed no associations between colorectal cancer risk and choline from free choline, glycerophosphocholine, phosphocholine, phosphatidylcholine, or sphingomyelin. Our data do not support that choline and betaine intake is inversely associated with colorectal cancer risk.","title":"Choline and betaine intake and the risk of colorectal cancer in men"},{"docid":"MED-1252","text":"The effect of substituting soy for animal protein in mixed diets was determined in young men with mildly elevated plasma cholesterol, 218 to 307 mg/dl. The diets were low in cholesterol, 200 mg/day, with 13 to 16% of energy as protein, 30 to 35% as fat, and a polyunsaturated to saturated fat ratio of 0.5. Of protein 65% was from either mixed animal proteins or isolated soy protein products made comparable by the addition of extracted animal fats. Fresh egg yolk was added to balance the cholesterol content of the diets. Proteins from grains and vegetables were identical in both menus and contributed about 35% of dietary protein. Twenty of 24 subjects decreased plasma cholesterol at the end of the protocol. Subjects were classified as responders or nonresponders as a function of greater or lesser than mean reduction in cholesterol for the groups. Mean decreases in plasma cholesterol, 16 and 13%, for responders in the animal and soy groups were significant, p less than 0.01 and 0.05, respectively. Responders in both groups had higher initial plasma cholesterol values than nonresponders. Although plasma high-density lipoprotein cholesterol decreased slightly, the high-density lipoprotein cholesterol to cholesterol ratio (high-density lipoprotein cholesterol/total cholesterol) remained constant for most individuals. The hypocholesterolemic effects were similar for both animal and soy protein (p less than 0.05) and fat (p less than 0.05) while on the experimental diet. All groups significantly decreased dietary cholesterol (p less than 0.001).","title":"Determinants of hypocholesterolemic response to soy and animal protein-based diets."},{"docid":"MED-3220","text":"Background Maintaining muscle mass while aging is important to prevent falls and fractures. Metabolic acidosis promotes muscle wasting, and the net acid load from diets that are rich in net acid–producing protein and cereal grains relative to their content of net alkali–producing fruit and vegetables may therefore contribute to a reduction in lean tissue mass in older adults. Objective We aimed to determine whether there was an association of 24-h urinary potassium and an index of fruit and vegetable content of the diet with the percentage lean body mass (%LBM) or change in %LBM in older subjects. Design Subjects were 384 men and women ≥65 y old who participated in a 3-y trial comparing calcium and vitamin D with placebo. Potassium was measured in 24-h urine collections at baseline. The %LBM, defined as total body nonfat, nonbone tissue weight ÷ weight × 100, was measured by using dual-energy X-ray absorptiometry at baseline and at 3 y. Physical activity, height, and weight were assessed at baseline and at 3 y. Results At baseline, the mean urinary potassium excretion was 67.0 ± 21.1 mmol/d. Urinary potassium (mmol/d) was significantly positively associated with %LBM at baseline (β = 0.033, P = 0.006; adjusted for sex, weight, and nitrogen excretion) but not with 3-y change in %LBM. Over the 3-y study, %LBM increased by 2.6 ± 3.6%. Conclusion Higher intake of foods rich in potassium, such as fruit and vegetables, may favor the preservation of muscle mass in older men and women.","title":"Alkaline diets favor lean tissue mass in older adults"},{"docid":"MED-3878","text":"Diet, nutritional status, and certain dietary supplements are postulated to influence the development and progression of prostate cancer. Angiogenesis and inflammation are central to tumor growth and progression, but the effect of diet on these processes remains uncertain. We explored changes in 50 plasma cytokines and angiogenic factors (CAFs) in 145 men with prostate cancer enrolled in a pre-operative, randomized controlled phase-II trial with four arms: control (usual diet); low-fat (LF) diet; flaxseed-supplemented (FS) diet; and flaxseed-supplemented, low-fat diet. The mean duration of dietary intervention was 30–31 days. Among the individual arms, the largest number of significant changes (baseline vs pre-operative follow-up) was observed in the LF arm, with 19 CAFs decreasing and one increasing (p<.05). Compared to the control arm, 6 CAFs—including pro-angiogenic factors (stromal-cell derived-1α and myeloid factors (granulocyte-colony-stimulating factor, macrophage colony-stimulating factor — all decreased in the LF arm compared to controls; 3 and 4 CAFs changed in the FS and FS+LF arms, respectively. Weight loss occurred in the LF arms and significantly correlated with VEGF decreases (P <0.001). The CAFs that changed in the LF arm are all known to be regulated by nuclear factor-kappa B (NF-κB), and a pathway analysis identified NF-κB as the most likely regulatory network associated with these changes in the LF arm, but not in the FS-containing arms. These results suggest that a low-fat diet without flaxseed may reduce levels of specific inflammatory cytokines and angiogenic factors and suggests that the NF-κB pathway may be a mediator of these changes.","title":"Effect of Low-fat Diets on Plasma Levels of NFκB-regulated Inflammatory Cytokines and Angiogenic Factors in Men with Prostate Cancer"},{"docid":"MED-2452","text":"A role for diet in the pathophysiology of asthma may be mediated by altered immune or antioxidant activity with consequent effects on airway inflammation. We evaluated associations between several dietary factors assessed by a semiquantitative food frequency questionnaire, and incidence of asthma over a 10-yr period in 77,866 women 34 to 68 yr of age. Women in the highest quintile of vitamin E intake from diet, but not from supplements, had a risk of 0.53 (95% confidence interval [CI] = 0.33 to 0.86) compared with women in the lowest quintile. This relationship, however, was attenuated when the contribution from nuts, a major source of vitamin E in these data and a possible allergen, was removed (relative risk = 0.74 [0.50 to 1.10], p for trend = 0.007). Positive associations were found for vitamins C and E from supplements, but appeared to be explained by women at high risk of asthma initiating use of vitamin supplements prior to diagnosis. A nonsignificant inverse association with carotene intake was noted, but no clear relations with asthma were demonstrated for intake of linoleic acid or omega-3 fatty acids. These data suggest that antioxidant supplementation and intake of various fats during adulthood are not important determinants of asthma, although vitamin E from diet may have a modest protective effect.","title":"A prospective study of diet and adult-onset asthma."},{"docid":"MED-2126","text":"Increased protein supply by feeding cow-milk-based infant formula in comparison to lower protein content of human milk is a well-recognized major risk factor of childhood obesity. However, there is yet no conclusive biochemical concept explaining the mechanisms of formula-induced childhood obesity. It is the intention of this article to provide the biochemical link between leucine-mediated signalling of mammalian milk proteins and adipogenesis as well as early adipogenic programming. Leucine has been identified as the predominant signal transducer of mammalian milk, which stimulates the nutrient-sensitive kinase mammalian target of rapamycin complex 1 (mTORC1). Leucine thus functions as a maternal-neonatal relay for mTORC1-dependent neonatal β-cell proliferation and insulin secretion. The mTORC1 target S6K1 plays a pivotal role in stimulation of mesenchymal stem cells to differentiate into adipocytes and to induce insulin resistance. It is of most critical concern that infant formulas provide higher amounts of leucine in comparison to human milk. Exaggerated leucine-mediated mTORC1-S6K1 signalling induced by infant formulas may thus explain increased adipogenesis and generation of lifelong elevated adipocyte numbers. Attenuation of mTORC1 signalling of infant formula by leucine restriction to physiologic lower levels of human milk offers a great chance for the prevention of childhood obesity and obesity-related metabolic diseases.","title":"Excessive Leucine-mTORC1-Signalling of Cow Milk-Based Infant Formula: The Missing Link to Understand Early Childhood Obesity"},{"docid":"MED-4060","text":"Heteroyclic aromatic amines (HAAs) are a class of hazardous chemicals that are receiving heightened attention as a risk factor for human cancer. HAAs arise during the cooking of meats, fish, and poultry, and several HAAs also occur in tobacco smoke condensate and diesel exhaust. Many HAAs are carcinogenic and induce tumors at multiple sites in rodents. A number of epidemiologic studies have reported that frequent consumption of well-done cooked meats containing HAAs can result in elevated risks for colon, prostate, and mammary cancers. Moreover, DNA adducts of HAAs have been detected in human tissues, demonstrating that HAAs induce genetic damage even though the concentrations of these compounds in cooked meats are generally in the low parts-per-billion (ppb) range. With recent improvements in sensitivity of mass spectrometry instrumentation, HAAs, their metabolites, and DNA adducts can be detected at trace amounts in biological fluids and tissues of humans. The incorporation of HAA biomarkers in epidemologic studies will help to clarify the role of these dietary genotoxicants in the etiology of human cancer.","title":"Formation and biochemistry of carcinogenic heterocyclic aromatic amines in cooked meats."},{"docid":"MED-2332","text":"Plants have evolved a variety of responses to elevated temperatures that minimize damage and ensure protection of cellular homeostasis. New information about the structure and function of heat stress proteins and molecular chaperones has become available. At the same time, transcriptome analysis of Arabidopsis has revealed the involvement of factors other than classical heat stress responsive genes in thermotolerance. Recent reports suggest that both plant hormones and reactive oxygen species also contribute to heat stress signaling. Additionally, an increasing number of mutants that have altered thermotolerance have extended our understanding of the complexity of the heat stress response in plants.","title":"Complexity of the heat stress response in plants."},{"docid":"MED-2333","text":"Until recently, the study and understanding of plant and animal signalling and response mechanisms have developed independently. Recent biochemical and molecular work is producing a growing list of elements involved in responses to biotic and abiotic stimuli that are very similar across kingdoms. Some of the more interesting examples of these include prostaglandin/octadecanoid-mediated responses to wounding, steroid-based signalling systems, and pathogen-recognition mechanisms. Some of these similarities probably represent evolutionary convergence; others may be ancestral to plants and animals. Ecological and evolutionary implications of such overlaps include the existence of pathogens that can cause disease in plants and animals, the ability of herbivores to manipulate plant responses, usurpation of microbial mechanisms and genes by herbivorous animals and plants, evolution of plant defenses exploiting shared signals in animals, and the medicinal use of plants by humans. Comparative study of the signalling and response mechanisms used by plants, animals, and microbes provides novel and useful insights to the ecology and evolution of interactions across kingdoms.","title":"Shared signals and the potential for phylogenetic espionage between plants and animals."},{"docid":"MED-3450","text":"Although assays for the most popular markers of exercise-induced oxidative stress may experience methodological flaws, there is sufficient credible evidence to suggest that exercise is accompanied by an increased generation of free radicals, resulting in a measurable degree of oxidative modifications to various molecules. However, the mechanisms responsible are unclear. A common assumption that increased mitochondrial oxygen consumption leads per se to increased reactive oxygen species (ROS) production is not supported by in vitro and in vivo data. The specific contributions of other systems (xanthine oxidase, inflammation, haem protein auto-oxidation) are poorly characterised. It has been demonstrated that ROS have the capacity to contribute to the development of muscle fatigue in situ, but there is still a lack of convincing direct evidence that ROS impair exercise performance in vivo in humans. It remains unclear whether exercise-induced oxidative modifications have little significance, induce harmful oxidative damage, or are an integral part of redox regulation. It is clear that ROS play important roles in numerous physiological processes at rest; however, the detailed physiological functions of ROS in exercise remain to be elucidated.","title":"Exercise-induced oxidative stress:myths, realities and physiological relevance."},{"docid":"MED-4040","text":"The consumption of cooked meat appears to predispose individuals to colonic cancer and heterocyclic aromatic amines (HA), formed during the cooking of meat, have been suggested as aetiological agents. Consumption of cruciferous vegetables is thought to protect against cancer. To study the effect of cruciferous vegetables on heterocyclic aromatic amine metabolism in man, a three-period, dietary intervention study has been carried out with 20 non-smoking Caucasian male subjects consuming cooked meat meals containing known amounts of these carcinogens. A high cruciferous vegetable diet (250 g each of Brussels sprouts and broccoli per day) was maintained during period 2 but such vegetables were excluded from periods 1 and 3. At the end of each period, subjects consumed a cooked meat meal and urinary excretion of the HA 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) was measured. Following a 12 day period of cruciferous vegetable consumption (period 2), induction of hepatic CYP1A2 activity was apparent from changes in the kinetics of caffeine metabolism. Excretion of MeIQx and PhIP in urine at the end of this period of the study was reduced by 23 and 21%, respectively, compared with period 1. This reduction in excretion is probably due to an increase in amine metabolism that might be expected given the observed increase in CYP1A2 activity, since this enzyme has been shown to be primarily responsible for the oxidative activation of MeIQx and PhIP in man. In period 2, urinary mutagenicity was increased relative to period 1 by 52 and 64% in the absence and presence, respectively, of a human liver microsomal activation system, yet no evidence was found of PhIP adduction to lymphocyte DNA, a potential biomarker of the activation process. After another 12 days without cruciferous vegetables (period 3 of the study), the kinetics of caffeine metabolism had returned to original values but excretion of MeIQx and PhIP was still reduced by 17 and 30%, respectively, and urinary mutagenicity (with metabolic activation) was still elevated compared with period 1. This prolonged response of amine metabolism to the cruciferous vegetable diet, shown especially with PhIP, suggests that enzyme systems other than CYP1A2 are involved and affected by a cruciferous vegetable diet.","title":"Effect of cruciferous vegetable consumption on heterocyclic aromatic amine metabolism in man."},{"docid":"MED-2479","text":"BACKGROUND: The prevalence of allergic diseases seems to have increased particularly over the past 35-40 years. Furthermore, allergic disease is less common among children in the formerly socialist countries of central and Eastern Europe as compared with Western Europe. It has been suggested that a reduced microbial stimulation during infancy and early childhood would result in a slower postnatal maturation of the immune system and development of an optimal balance between TH1- and TH2-like immunity. AIMS: To test the hypothesis that allergic disease among children may be associated with differences in their intestinal microflora in two countries with a low (Estonia) and a high (Sweden) prevalence of allergy. METHODS: From a prospective study of the development of allergy in relation to environmental factors, 29 Estonian and 33 Swedish 2-year-old children were selected. They were either nonallergic (n = 36) or had a confirmed diagnosis of allergy (n = 27) as verified by typical history and at least one positive skin prick test to egg or cow's milk. Weighed samples of faeces were serially diluted (10-2-10-9) and grown under anaerobic conditions. The counts of the various genera and species were calculated for each child. In addition, the relative amounts of the particular microbes were expressed as a proportion of the total count. RESULTS: The allergic children in Estonia and Sweden were less often colonized with lactobacilli (P < 0.01), as compared with the nonallergic children in the two countries. In contrast, the allergic children harboured higher counts of aerobic micro-organisms (P < 0. 05), particularly coliforms (P < 0.01) and Staphylococcus aureus (P < 0.05). The proportions of aerobic bacteria of the intestinal flora were also higher in the allergic children (P < 0.05), while the opposite was true for anaerobes (P < 0.05). Similarly, in the allergic children the proportions of coliforms were higher (P < 0. 05) and bacteroides lower (P < 0.05) than in the nonallergic children. CONCLUSIONS: Differences in the indigenous intestinal flora might affect the development and priming of the immune system in early childhood, similar to what has been shown in rodents. The role of intestinal microflora in relation to the development of infant immunity and the possible consequences for allergic diseases later in life requires further study, particularly as it would be readily available for intervention as a means for primary prevention of allergy by the administration of probiotic bacteria.","title":"The intestinal microflora in allergic Estonian and Swedish 2-year-old children."},{"docid":"MED-1718","text":"The number of cancer cases caused by being obese is estimated to be 20% with the increased risk of malignancies being influenced by diet, weight change, and body fat distribution together with physical activity. Reports from the International Agency for Research into Cancer and the World Cancer Research Fund (WCRF) have shown that the strongest evidence exists for an association of obesity with the following cancer types: endometrial, esophageal adenocarcinoma, colorectal, postmenopausal breast, prostate, and renal, whereas the less common malignancies are leukemia, non-Hodgkin's lymphoma, multiple myeloma, malignant melanoma, and thyroid tumours. To be able to develop novel methods in prevention and treatment, we first must understand the underlying processes which link cancer to obesity. Four main systems have been identified as potential producers of cancer in obesity: insulin, insulin-like growth factor-I, sex steroids, and adipokines. Various novel candidate mechanisms have been proposed: chronic inflammation, oxidative stress, crosstalk between tumour cells and surrounding adipocytes, migrating adipose stromal cells, obesity-induced hypoxia, shared genetic susceptibility, and the functional defeat of immune function. Herein, we review the major pathogenic links between obesity and susceptibility to cancer.","title":"Obesity as a Major Risk Factor for Cancer"},{"docid":"MED-1717","text":"BACKGROUND: Excess bodyweight, expressed as increased body-mass index (BMI), is associated with the risk of some common adult cancers. We did a systematic review and meta-analysis to assess the strength of associations between BMI and different sites of cancer and to investigate differences in these associations between sex and ethnic groups. METHODS: We did electronic searches on Medline and Embase (1966 to November 2007), and searched reports to identify prospective studies of incident cases of 20 cancer types. We did random-effects meta-analyses and meta-regressions of study-specific incremental estimates to determine the risk of cancer associated with a 5 kg/m2 increase in BMI. FINDINGS: We analysed 221 datasets (141 articles), including 282,137 incident cases. In men, a 5 kg/m2 increase in BMI was strongly associated with oesophageal adenocarcinoma (RR 1.52, p<0.0001) and with thyroid (1.33, p=0.02), colon (1.24, p<0.0001), and renal (1.24, p <0.0001) cancers. In women, we recorded strong associations between a 5 kg/m2 increase in BMI and endometrial (1.59, p<0.0001), gallbladder (1.59, p=0.04), oesophageal adenocarcinoma (1.51, p<0.0001), and renal (1.34, p<0.0001) cancers. We noted weaker positive associations (RR <1.20) between increased BMI and rectal cancer and malignant melanoma in men; postmenopausal breast, pancreatic, thyroid, and colon cancers in women; and leukaemia, multiple myeloma, and non-Hodgkin lymphoma in both sexes. Associations were stronger in men than in women for colon (p<0.0001) cancer. Associations were generally similar in studies from North America, Europe and Australia, and the Asia-Pacific region, but we recorded stronger associations in Asia-Pacific populations between increased BMI and premenopausal (p=0.009) and postmenopausal (p=0.06) breast cancers. INTERPRETATION: Increased BMI is associated with increased risk of common and less common malignancies. For some cancer types, associations differ between sexes and populations of different ethnic origins. These epidemiological observations should inform the exploration of biological mechanisms that link obesity with cancer.","title":"Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies."},{"docid":"MED-3228","text":"A precise understanding of the role of dietary protein in bone health has been evasive despite decades of research. It is known that a dietary acid load is harmful to bone, and sulfur-containing amino acids are metabolized to provide such an acid load. It is also known that protein elevates urine calcium loss. However, recent clinical studies and a meta-analysis have indicated either no effect or a modest benefit associated with higher protein intakes. These contradictory considerations may be explained by the existence of a two-faced relationship between protein and bone, with simultaneous positive and negative pathways. In opposition to the negative effects of dietary acid load, protein may exert positive effects related to improving calcium absorption, increasing insulin-like growth factor 1, or improving lean body mass, which, in turn, improves bone strength. Putative mechanisms behind these pathways are reviewed here, and some limitations in the historical literature as well as suggested measures to counter these in the future are identified. When positive and negative pathways are considered in tandem, protein may offer modest benefits to bone in the presence of adequate dietary calcium and acid-neutralizing fruits and vegetables. © 2011 International Life Sciences Institute.","title":"Dietary protein and bone health: harmonizing conflicting theories."},{"docid":"MED-3318","text":"Smoking is an established risk factor for pancreatic cancer; however, detailed examination of the association of smoking intensity, smoking duration, and cumulative smoking dose with pancreatic cancer is limited. The authors analyzed pooled data from the international Pancreatic Cancer Cohort Consortium nested case-control study (1,481 cases, 1,539 controls). Odds ratios and 95% confidence intervals were calculated by using unconditional logistic regression. Smoking intensity effects were examined with an excess odds ratio model that was linear in pack-years and exponential in cigarettes smoked per day and its square. When compared with never smokers, current smokers had a significantly elevated risk (odds ratio (OR) = 1.77, 95% confidence interval (CI): 1.38, 2.26). Risk increased significantly with greater intensity (≥30 cigarettes/day: OR = 1.75, 95% CI: 1.27, 2.42), duration (≥50 years: OR = 2.13, 95% CI: 1.25, 3.62), and cumulative smoking dose (≥40 pack-years: OR = 1.78, 95% CI: 1.35, 2.34). Risk more than 15 years after smoking cessation was similar to that for never smokers. Estimates of excess odds ratio per pack-year declined with increasing intensity, suggesting greater risk for total exposure delivered at lower intensity for longer duration than for higher intensity for shorter duration. This finding and the decline in risk after smoking cessation suggest that smoking has a late-stage effect on pancreatic carcinogenesis.","title":"Cigarette Smoking and Pancreatic Cancer: A Pooled Analysis From the Pancreatic Cancer Cohort Consortium"},{"docid":"MED-2207","text":"The objective of this study was to investigate the antiproliferative effect and the mechanism of trypsin inhibitor (TI) from sweet potato [Ipomoea batatas (L.) Lam. 'Tainong 57'] storage roots on NB4 promyelocytic leukemia cells. The results showed that TI inhibited cellular growth of NB4 promyelocytic leukemia cells in a time-dependent and dose-dependent manner, and treatment for 72 h induced a marked inhibition of cellular growth, showing an IC50 of 57.1 +/- 8.26 microg/mL. TI caused cell cycle arrest at the G1 phase as determined by flow cytometric analysis and apoptosis as shown by DNA laddering. TI-induced cell apoptosis involved p53, Bcl-2, Bax, and cytochrome c protein in NB4 cells. P53 and Bax proteins were accumulated, and antiapoptotic molecule Bcl-2 was decreased in the tested cells in a time-dependent manner during TI treatment. TI also induced a substantial release of cytochrome c from the mitochondria into the cytosol. Hence, TI induced apoptosis in NB4 cells through a mitochondria-dependent pathway, which was associated with the activation of caspase-3 and -8. These results demonstrated that TI induces NB4 cell apoptosis through the inhibition of cell growth and the activation of the pathway of caspase-3 and -8 cascades.","title":"Growth inhibition and induction of apoptosis in NB4 promyelocytic leukemia cells by trypsin inhibitor from sweet potato storage roots."},{"docid":"MED-1186","text":"We investigated the effect of resistant starch (RS) on markers of colonic protein metabolism. Eleven subjects participated in a randomized crossover study in which they consumed either high-RS (39 +/- 3 g/d, -chi +/- SEM) or low-RS (5 +/- 0.4 g/d) diets for 3 wk. All other macronutrients were kept constant. During the high-RS diet daily excretion of fecal nitrogen increased from 1.84 +/- 0.15 to 2.86 +/- 0.42 g/d (P < 0.01) and excretion of fecal phenols fell from 9.2 +/- 1.4 to 5.3 +/- 0.8 mg/d (P < 0.01). Fecal concentrations of ammonia decreased from 397 +/- 33 to 278 +/- 49 microgram/g (P < 0.01) and phenols decreased from 69 +/- 8 to 39 +/- 10 microgram/g (P < 0.001). Daily output of urinary ammonia, urea, phenols, and total nitrogen did not change significantly, but pH decreased from 6.4 +/- 0.1 to 6.2 +/- 0.1 (P < 0.05) during the high-RS period. These results suggest that RS significantly attenuates the accumulation of potentially harmful byproducts of protein fermentation in the human colon.","title":"Resistant starch lowers fecal concentrations of ammonia and phenols in humans."},{"docid":"MED-3279","text":"Various pesticides are being used to destabilize, perturb, or inhibit crucial biochemical and physiological targets related to metabolism, growth, development, nervous communication, or behavior in pestiferous organisms. Chitin is an eukaryotic extracellular aminosugar biopolymer, massively produced by most fungal systems and by invertebrates, notably arthropods. Being an integral supportive component in fungal cell wall, insect cuticle, and nematode egg shell, chitin has been considered as a selective target for pesticide action. Throughout the elaborate processes of chitin formation and deposition, only the polymerization events associated with the cell membrane compartment are so far available for chemical interference. Currently, the actinomycetes-derived nucleoside peptide fungicides such as the polyoxins and the insecticidal benzoylaryl ureas have reached commercial pesticide status. The polyoxins and other structurally-related antibiotics like nikkomycins are strong competitive inhibitors of the polymerizing enzyme chitin synthase. The exact biochemical lesion inflicted by the benzoylaryl ureas is still elusive, but a post-polymerization event, such as translocation of chitin chains across the cell membrane, is suggested. Hydrolytic degradation of the chitin polymer is essential for hyphal growth, branching, and septum formation in fungal systems as well as for the normal molting of arthropods. Recently, insect chitinase activity was strongly and specifically suppressed by allosamidin, an actimomycetes-derived metabolite. In part, the defense mechanism in plants against invasion of pathogens is associated with induced chitinases. Chitin, chitosan, and their oligomers are able to act as elicitors which induce enhanced levels of chitinases in various plants. Lectins which bind to N-acetyl-D-glucosamine strongly interfere with fungal and insect chitin synthases. Plant lectins with similar properties may be involved in plant-pathogen interaction inter alia by suppressing fungal invasion.","title":"Chitin synthesis and degradation as targets for pesticide action."},{"docid":"MED-4233","text":"OBJECTIVES: Dietary fat and fiber affect hormonal levels and may influence cancer progression. Flaxseed is a rich source of lignan and omega-3 fatty acids and may thwart prostate cancer. The potential effects of flaxseed may be enhanced with concomitant fat restriction. We undertook a pilot study to explore whether a flaxseed-supplemented, fat-restricted diet could affect the biomarkers of prostatic neoplasia. METHODS: Twenty-five patients with prostate cancer who were awaiting prostatectomy were instructed on a low-fat (20% of kilocalories or less), flaxseed-supplemented (30 g/day) diet. The baseline and follow-up levels of prostate-specific antigen, testosterone, free androgen index, and total serum cholesterol were determined. The tumors of diet-treated patients were compared with those of historic cases (matched by age, race, prostate-specific antigen level at diagnosis, and biopsy Gleason sum) with respect to apoptosis (terminal deoxynucleotidyl transferase [TdT]-mediated dUTP-biotin nick end-labeling [TUNEL]) and proliferation (MIB-1). RESULTS: The average duration on the diet was 34 days (range 21 to 77), during which time significant decreases were observed in total serum cholesterol (201 +/- 39 mg/dL to 174 +/- 42 mg/dL), total testosterone (422 +/- 122 ng/dL to 360 +/- 128 ng/dL), and free androgen index (36.3% +/- 18.9% to 29.3% +/- 16.8%) (all P <0.05). The baseline and follow-up levels of prostate-specific antigen were 8.1 +/- 5.2 ng/mL and 8.5 +/- 7.7 ng/mL, respectively, for the entire sample (P = 0.58); however, among men with Gleason sums of 6 or less (n = 19), the PSA values were 7.1 +/- 3.9 ng/mL and 6.4 +/- 4.1 ng/mL (P = 0.10). The mean proliferation index was 7.4 +/- 7.8 for the historic controls versus 5.0 +/- 4.9 for the diet-treated patients (P = 0.05). The distribution of the apoptotic indexes differed significantly (P = 0.01) between groups, with most historic controls exhibiting TUNEL categorical scores of 0; diet-treated patients largely exhibited scores of 1. Both the proliferation rate and apoptosis were significantly associated with the number of days on the diet (P = 0.049 and P = 0.017, respectively). CONCLUSIONS: These pilot data suggest that a flaxseed-supplemented, fat-restricted diet may affect prostate cancer biology and associated biomarkers. Further study is needed to determine the benefit of this dietary regimen as either a complementary or preventive therapy.","title":"Pilot study of dietary fat restriction and flaxseed supplementation in men with prostate cancer before surgery: exploring the effects on hormonal l..."},{"docid":"MED-3237","text":"The modern Western-type diet is deficient in fruits and vegetables and contains excessive animal products, generating the accumulation of non-metabolizable anions and a lifespan state of overlooked metabolic acidosis, whose magnitude increases progressively with aging due to the physiological decline in kidney function. In response to this state of diet-derived metabolic acidosis, the kidney implements compensating mechanisms aimed to restore the acid-base balance, such as the removal of the non-metabolizable anions, the conservation of citrate, and the enhancement of kidney ammoniagenesis and urinary excretion of ammonium ions. These adaptive processes lower the urine pH and induce an extensive change in urine composition, including hypocitraturia, hypercalciuria, and nitrogen and phosphate wasting. Low urine pH predisposes to uric acid stone formation. Hypocitraturia and hypercalciuria are risk factors for calcium stone disease. Even a very mild degree of metabolic acidosis induces skeletal muscle resistance to the insulin action and dietary acid load may be an important variable in predicting the metabolic abnormalities and the cardiovascular risk of the general population, the overweight and obese persons, and other patient populations including diabetes and chronic kidney failure. High dietary acid load is more likely to result in diabetes and systemic hypertension and may increase the cardiovascular risk. Results of recent observational studies confirm an association between insulin resistance and metabolic acidosis markers, including low serum bicarbonate, high serum anion gap, hypocitraturia, and low urine pH. Copyright © 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.","title":"Diet-induced metabolic acidosis."},{"docid":"MED-5116","text":"BACKGROUND: Laboratory research and a growing number of epidemiologic studies have provided evidence for a reduced risk of breast cancer associated with dietary intake of certain classes of flavonoids. However, the effects of flavonoids on survival are not known. In a population-based cohort of breast cancer patients, we investigated whether dietary flavonoid intake before diagnosis is associated with subsequent survival. METHODS: Women ages 25 to 98 years who were newly diagnosed with a first primary invasive breast cancer between August 1, 1996, and July 31, 1997, and participated in a population-based, case-control study (n=1,210) were followed for vital status through December 31, 2002. At the case-control interview conducted shortly after diagnosis, respondents completed a FFQ that assessed dietary intake in the previous 12 months. All-cause mortality (n=173 deaths) and breast cancer-specific mortality (n=113 deaths) were determined through the National Death Index. RESULTS: Reduced hazard ratios [age- and energy-adjusted hazard ratio (95% confidence interval)] for all-cause mortality were observed among premenopausal and postmenopausal women for the highest quintile of intake, compared with the lowest, for flavones [0.63 (0.41-0.96)], isoflavones [0.52 (0.33-0.82)], and anthocyanidins [0.64 (0.42-0.98)]. No significant trends in risk were observed. Results were similar for breast cancer-specific mortality only. CONCLUSION: Mortality may be reduced in association with high levels of dietary flavones and isoflavones among postmenopausal U.S. breast cancer patients. Larger studies are needed to confirm our findings.","title":"Dietary flavonoid intake and breast cancer survival among women on Long Island."},{"docid":"MED-2502","text":"Dietary restriction (DR) without malnutrition is widely regarded to be a universal mechanism for prolonging lifespan. It is generally believed that the benefits of DR arise from eating fewer calories (termed caloric restriction, CR). Here we argue that, rather than calories, the key determinant of the relationship between diet and longevity is the balance of protein to non-protein energy ingested. This ratio affects not only lifespan, but also total energy intake, metabolism, immunity and the likelihood of developing obesity and associated metabolic disorders. Among various possible mechanisms linking macronutrient balance to lifespan, the nexus between the TOR and AMPK signaling pathways is emerging as a central coordinator.","title":"Macronutrient balance and lifespan"},{"docid":"MED-1227","text":"To correct methodologic flaws (Type II error, confounding variables, and nonblinding) in previous studies relating infant feeding to later obesity, we conducted case-control studies of 639 patients 12 to 18 years of age attending our Adolescent Clinic, and 533 similarly aged healthy children attending a Montreal high school. Each subject was classified as either obese, overweight, or nonobese based on measurements of height, weight, and triceps and subscapular skinfolds. Feeding history, family history, and demographic data were later ascertained \"blindly\" by telephone interview. Analysis of the raw data revealed a significantly elevated estimated relative risk of not breast-feeding and a significant trend for rates of breast-feeding among the three weight groups. The magnitude of the protective effect appeared to rise slightly with increased duration of breast-feeding. Delayed introduction of solid foods provided little if any additional benefit. Several demographic and clinical variables proved to be confounding, but the significant protective effect of breast-feeding persisted even after controlling for confounders. We conclude that breast-feeding does protect against later obesity and attribute the conflicting results of previous studies to insufficient attention to methodologic standards.","title":"Do breast-feeding and delayed introduction of solid foods protect against subsequent obesity?"},{"docid":"MED-4163","text":"OBJECTIVE: The health benefits of vegetarian diets are well-recognized; however, long-term adherence to these diets may be associated with nutrient inadequacies, particularly vitamins B12 and D, calcium, iron, zinc, and protein. The dietary reference intakes (DRIs) expert panels recommended adjustments to the iron, zinc, and calcium DRIs for vegetarians to account for decreased bioavailability, but no adjustments were considered necessary for the protein DRI under the assumption that vegetarians consume about 50% of protein from animal (dairy/egg) sources. This study examined dietary protein sources in a convenience sample of 21 young adult vegetarian women who completed food logs on 4 consecutive days (3 weekdays and 1 weekend day). METHODS: The daily contribution percentages of protein consumed from cereals, legumes, nuts/seeds, fruits/vegetables, and dairy/egg were computed, and the protein digestibility corrected amino acid score of the daily diets was calculated. RESULTS: The calculated total dietary protein digestibility score for participants was 82 ± 1%, which differed significantly (P < 0.001) from the DRI reference score, 88%, and the 4-d average protein digestibility corrected amino acid score for the sample was 80 ± 2%, which also differed significantly (P < 0.001) from the DRI reference value, 100%. The analyses indicated that animal protein accounted for only 21% of dietary protein. CONCLUSION: This research suggests that the protein DRI for vegetarians consuming less than the expected amounts of animal protein (45% to 50% of total protein) may need to be adjusted from 0.8 to about 1.0 g/kg to account for decreased protein bioavailability. Copyright © 2011 Elsevier Inc. All rights reserved.","title":"Protein dietary reference intakes may be inadequate for vegetarians if low amounts of animal protein are consumed."},{"docid":"MED-2082","text":"BACKGROUND: Reliable and timely information on the leading causes of death in populations, and how these are changing, is a crucial input into health policy debates. In the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010), we aimed to estimate annual deaths for the world and 21 regions between 1980 and 2010 for 235 causes, with uncertainty intervals (UIs), separately by age and sex. METHODS: We attempted to identify all available data on causes of death for 187 countries from 1980 to 2010 from vital registration, verbal autopsy, mortality surveillance, censuses, surveys, hospitals, police records, and mortuaries. We assessed data quality for completeness, diagnostic accuracy, missing data, stochastic variations, and probable causes of death. We applied six different modelling strategies to estimate cause-specific mortality trends depending on the strength of the data. For 133 causes and three special aggregates we used the Cause of Death Ensemble model (CODEm) approach, which uses four families of statistical models testing a large set of different models using different permutations of covariates. Model ensembles were developed from these component models. We assessed model performance with rigorous out-of-sample testing of prediction error and the validity of 95% UIs. For 13 causes with low observed numbers of deaths, we developed negative binomial models with plausible covariates. For 27 causes for which death is rare, we modelled the higher level cause in the cause hierarchy of the GBD 2010 and then allocated deaths across component causes proportionately, estimated from all available data in the database. For selected causes (African trypanosomiasis, congenital syphilis, whooping cough, measles, typhoid and parathyroid, leishmaniasis, acute hepatitis E, and HIV/AIDS), we used natural history models based on information on incidence, prevalence, and case-fatality. We separately estimated cause fractions by aetiology for diarrhoea, lower respiratory infections, and meningitis, as well as disaggregations by subcause for chronic kidney disease, maternal disorders, cirrhosis, and liver cancer. For deaths due to collective violence and natural disasters, we used mortality shock regressions. For every cause, we estimated 95% UIs that captured both parameter estimation uncertainty and uncertainty due to model specification where CODEm was used. We constrained cause-specific fractions within every age-sex group to sum to total mortality based on draws from the uncertainty distributions. FINDINGS: In 2010, there were 52·8 million deaths globally. At the most aggregate level, communicable, maternal, neonatal, and nutritional causes were 24·9% of deaths worldwide in 2010, down from 15·9 million (34·1%) of 46·5 million in 1990. This decrease was largely due to decreases in mortality from diarrhoeal disease (from 2·5 to 1·4 million), lower respiratory infections (from 3·4 to 2·8 million), neonatal disorders (from 3·1 to 2·2 million), measles (from 0·63 to 0·13 million), and tetanus (from 0·27 to 0·06 million). Deaths from HIV/AIDS increased from 0·30 million in 1990 to 1·5 million in 2010, reaching a peak of 1·7 million in 2006. Malaria mortality also rose by an estimated 19·9% since 1990 to 1·17 million deaths in 2010. Tuberculosis killed 1·2 million people in 2010. Deaths from non-communicable diseases rose by just under 8 million between 1990 and 2010, accounting for two of every three deaths (34·5 million) worldwide by 2010. 8 million people died from cancer in 2010, 38% more than two decades ago; of these, 1·5 million (19%) were from trachea, bronchus, and lung cancer. Ischaemic heart disease and stroke collectively killed 12·9 million people in 2010, or one in four deaths worldwide, compared with one in five in 1990; 1·3 million deaths were due to diabetes, twice as many as in 1990. The fraction of global deaths due to injuries (5·1 million deaths) was marginally higher in 2010 (9·6%) compared with two decades earlier (8·8%). This was driven by a 46% rise in deaths worldwide due to road traffic accidents (1·3 million in 2010) and a rise in deaths from falls. Ischaemic heart disease, stroke, chronic obstructive pulmonary disease (COPD), lower respiratory infections, lung cancer, and HIV/AIDS were the leading causes of death in 2010. Ischaemic heart disease, lower respiratory infections, stroke, diarrhoeal disease, malaria, and HIV/AIDS were the leading causes of years of life lost due to premature mortality (YLLs) in 2010, similar to what was estimated for 1990, except for HIV/AIDS and preterm birth complications. YLLs from lower respiratory infections and diarrhoea decreased by 45-54% since 1990; ischaemic heart disease and stroke YLLs increased by 17-28%. Regional variations in leading causes of death were substantial. Communicable, maternal, neonatal, and nutritional causes still accounted for 76% of premature mortality in sub-Saharan Africa in 2010. Age standardised death rates from some key disorders rose (HIV/AIDS, Alzheimer's disease, diabetes mellitus, and chronic kidney disease in particular), but for most diseases, death rates fell in the past two decades; including major vascular diseases, COPD, most forms of cancer, liver cirrhosis, and maternal disorders. For other conditions, notably malaria, prostate cancer, and injuries, little change was noted. INTERPRETATION: Population growth, increased average age of the world's population, and largely decreasing age-specific, sex-specific, and cause-specific death rates combine to drive a broad shift from communicable, maternal, neonatal, and nutritional causes towards non-communicable diseases. Nevertheless, communicable, maternal, neonatal, and nutritional causes remain the dominant causes of YLLs in sub-Saharan Africa. Overlaid on this general pattern of the epidemiological transition, marked regional variation exists in many causes, such as interpersonal violence, suicide, liver cancer, diabetes, cirrhosis, Chagas disease, African trypanosomiasis, melanoma, and others. Regional heterogeneity highlights the importance of sound epidemiological assessments of the causes of death on a regular basis. FUNDING: Bill & Melinda Gates Foundation. Copyright © 2012 Elsevier Ltd. All rights reserved.","title":"Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease S..."},{"docid":"MED-5110","text":"Americans consume billions of hotdogs per year resulting in more than a billion dollars in retail sales. Package labels typically list some type of meat as the primary ingredient. The purpose of this study is to assess the meat and water content of several hotdog brands to determine if the package labels are accurate. Eight brands of hotdogs were evaluated for water content by weight. A variety of routine techniques in surgical pathology including routine light microscopy with hematoxylin-eosin-stained sections, special staining, immunohistochemistry, and electron microscopy were used to assess for meat content and for other recognizable components. Package labels indicated that the top-listed ingredient in all 8 brands was meat; the second listed ingredient was water (n = 6) and another type of meat (n = 2). Water comprised 44% to 69% (median, 57%) of the total weight. Meat content determined by microscopic cross-section analysis ranged from 2.9% to 21.2% (median, 5.7%). The cost per hotdog ($0.12-$0.42) roughly correlated with meat content. A variety of tissues were observed besides skeletal muscle including bone (n = 8), collagen (n = 8), blood vessels (n = 8), plant material (n = 8), peripheral nerve (n = 7), adipose (n = 5), cartilage (n = 4), and skin (n = 1). Glial fibrillary acidic protein immunostaining was not observed in any of the hotdogs. Lipid content on oil red O staining was graded as moderate in 3 hotdogs and marked in 5 hotdogs. Electron microscopy showed recognizable skeletal muscle with evidence of degenerative changes. In conclusion, hotdog ingredient labels are misleading; most brands are more than 50% water by weight. The amount of meat (skeletal muscle) in most brands comprised less than 10% of the cross-sectional surface area. More expensive brands generally had more meat. All hotdogs contained other tissue types (bone and cartilage) not related to skeletal muscle; brain tissue was not present.","title":"Applying morphologic techniques to evaluate hotdogs: what is in the hotdogs we eat?"},{"docid":"MED-3139","text":"Background: Soy isoflavones have antiestrogenic and anticancer properties but also possess estrogen-like properties, which has raised concern about soy food consumption among breast cancer survivors. Objective: We prospectively evaluated the association between postdiagnosis soy food consumption and breast cancer outcomes among US and Chinese women by using data from the After Breast Cancer Pooling Project. Design: The analysis included 9514 breast cancer survivors with a diagnosis of invasive breast cancer between 1991 and 2006 from 2 US cohorts and 1 Chinese cohort. Soy isoflavone intake (mg/d) was measured with validated food-frequency questionnaires. HRs and 95% CIs were estimated by using delayed-entry Cox regression models, adjusted for sociodemographic, clinical, and lifestyle factors. Results: After a mean follow-up of 7.4 y, we identified 1171 total deaths (881 from breast cancer) and 1348 recurrences. Despite large differences in soy isoflavone intake by country, isoflavone consumption was inversely associated with recurrence among both US and Chinese women, regardless of whether data were analyzed separately by country or combined. No heterogeneity was observed. In the pooled analysis, consumption of ≥10 mg isoflavones/d was associated with a nonsignificant reduced risk of all-cause (HR: 0.87; 95% CI: 0.70, 1.10) and breast cancer–specific (HR: 0.83; 95% CI: 0.64, 1.07) mortality and a statistically significant reduced risk of recurrence (HR: 0.75; 95% CI: 0.61, 0.92). Conclusion: In this large study of combined data on US and Chinese women, postdiagnosis soy food consumption of ≥10 mg isoflavones/d was associated with a nonsignificant reduced risk of breast cancer–specific mortality and a statistically significant reduced risk of recurrence. One of the studies included in the After Breast Cancer Pooling Project, the Women's Healthy Eating & Living Study, was registered at clinicaltrials.gov as NCT00003787.","title":"Soy food intake after diagnosis of breast cancer and survival: an in-depth analysis of combined evidence from cohort studies of US and Chinese women"},{"docid":"MED-4203","text":"Oxygen is vital for most organisms but, paradoxically, damages key biological sites. Oxygenic threat is met by antioxidants that evolved in parallel with our oxygenic atmosphere. Plants employ antioxidants to defend their structures against reactive oxygen species (ROS; oxidants) produced during photosynthesis. The human body is exposed to these same oxidants, and we have also evolved an effective antioxidant system. However, this is not infallible. ROS breach defences, oxidative damage ensues, accumulates with age, and causes a variety of pathological changes. Plant-based, antioxidant-rich foods traditionally formed the major part of the human diet, and plant-based dietary antioxidants are hypothesized to have an important role in maintaining human health. This hypothesis is logical in evolutionary terms, especially when we consider the relatively hypoxic environment in which humans may have evolved. In this paper, the human diet is discussed briefly in terms of its evolutionary development, different strategies of antioxidant defence are outlined, and evolution of dietary antioxidants is discussed from the perspectives of plant need and our current dietary requirements. Finally, possibilities in regard to dietary antioxidants, evolution, and human health are presented, and an evolutionary cost-benefit analysis is presented in relation to why we lost the ability to make ascorbic acid (vitamin C) although we retained an absolute requirement for it.","title":"Evolution of dietary antioxidants."},{"docid":"MED-2352","text":"BACKGROUND: Carbohydrate-specific IgE antibodies present on nonprimate mammalian proteins were incriminated recently in delayed meat anaphylaxis. The aim of this study was to explore whether anaphylaxis to mammalian kidney is also associated with galactose-α-1,3-galactose (αGal)-specific IgE. METHODS: Fourteen patients with anaphylaxis to pork or beef kidney underwent prick tests to meat and kidney. Some patients also underwent skin tests to Erbitux(®) (cetuximab). IgE antibodies to αGal, swine urine proteins, beef and pork meat, serum albumin proteins, cat, and rFel d 1 were measured by ImmunoCAP(®). The αGal levels were estimated in meats and kidney by ELISA inhibition assay. Cross-reactivity between αGal and pork kidney was studied with the ImmunoCAP(®) inhibition assay. RESULTS: Among the 14 patients, 12 presented with anaphylactic shock. Reactions occurred within 2 h from exposure in 67% of patients. Associated risk factors were observed in 10 cases, and alcohol was the main cofactor. Three patients underwent an oral challenge to pork kidney, and anaphylaxis occurred after ingestion of small quantities (1-2 g). Prick tests to kidney were positive in 54% of patients. All tested patients showed positive skin tests to Erbitux(®). All patients tested positive for IgE to αGal, with levels ranging from 0.4 to 294 kU/l. IgE binding to αGal was inhibited by raw pork kidney extract (mean, 77%; range, 55-87%), which showed a high amount of αGal determinants. CONCLUSIONS: Pork or beef kidney anaphylaxis is related to αGal IgE. Its peculiar severity could be due to an elevated content of αGal epitopes in kidney. © 2012 John Wiley & Sons A/S.","title":"Anaphylaxis to pork kidney is related to IgE antibodies specific for galactose-alpha-1,3-galactose."},{"docid":"MED-3129","text":"BRCA1 mutations have been associated with hereditary breast cancer only. Recent studies indicate that a subgroup of sporadic breast cancer might also be associated with reduction in BRCA1 mRNA levels and protein expression. However, the mechanism of reduced mRNA and protein expression is yet not fully elucidated. This study aims to assess BRCA1 protein expression and the role of BRCA1 promoter methylation in sporadic breast cancer in North Indian population and to correlate these with known prognostic factors and molecular profiles of breast cancer. BRCA1 protein expression was normal (>50 % tumour cells) in 41 (43 %) cases, reduced (20-50 % tumour cells) in 33 (35 %) cases and absent/markedly reduced (<20 % tumour cells) in 21 (22.1 %) cases. Cases which were negative for BRCA1 protein were more frequently positive for basal markers (29 versus 5 %) and were more often ER-negative (62 versus 39 %) than BRCA1-positive tumours. Methylation of BRCA1 promoter region was seen in 11/45 cases (24 %). All 11 cases showing BRCA1 methylation had absent (eight cases) or reduced (three cases) BRCA1 protein expression. BRCA1 protein-negative tumours were more frequently basal marker-positive and ER-negative, highlighting the 'BRCAness' of sporadic breast cancer with loss of BRCA1 protein expression through promoter hypermethylation similar to hereditary breast cancer with BRCA1 mutations. Loss of BRCA1 in sporadic breast cancer suggests that therapeutics targeting BRCA1 pathway in hereditary breast cancer like PARP inhibitors might be used as therapeutic targets for sporadic breast tumours.","title":"BRCA1-methylated sporadic breast cancers are BRCA-like in showing a basal phenotype and absence of ER expression."},{"docid":"MED-2356","text":"Background In 2009, we reported a novel form of delayed anaphylaxis to red meat, which is related to serum IgE antibodies to the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal). Most of these patients had tolerated meat for many years previously. The implication is that some exposure in adult life had stimulated the production of these IgE antibodies. Objectives To investigate possible causes of this IgE antibody response, focusing on evidence related to tick bites, which are common in the region where these reactions occur. Methods Serum assays were carried out using biotinylated proteins and extracts bound to a streptavidin ImmunoCAP. Results Prospective studies on IgE antibodies in three subjects following tick bites showed an increase in IgE to alpha-gal of twenty-fold or greater. Other evidence included i) a strong correlation between histories of tick bites and IgE to alpha-gal (χ2=26.8, p<0.001), ii) evidence that these IgE antibodies are common in areas where the tick Amblyomma americanum is common, and iii) a significant correlation between IgE antibodies to alpha-gal and IgE antibodies to proteins derived from A. americanum (rs=0.75, p<0.001). Conclusion The results presented here provide evidence that tick bites are a cause, or possibly the only cause, of IgE specific for alpha-gal in this area of the United States. Both the number of subjects becoming sensitized and the titer of IgE antibodies to alpha-gal are striking. Here we report the first example of a response to an ectoparasite giving rise to an important form of food allergy.","title":"The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose"},{"docid":"MED-4212","text":"Soya foods may protect against the development of breast cancer. Insulin-like growth factor (IGF)-1 is under investigation as a possible link between nutrition and cancer. We examined the effect of soya foods on circulating IGF-1 and IGF binding protein (BP)-3 levels among 196 healthy premenopausal women in a 2-year randomised nutritional trial. The intervention group consumed two daily servings of soya foods including tofu, soya milk, soya nuts and soya protein powder (equivalent to 50 mg isoflavones and 5-22 g soya protein per serving); the controls maintained their regular diet. Five serum samples at baseline, 3, 6, 12, and 24 months were collected in the morning during the luteal phase and analysed for IGF-1 and IGFBP-3 by double-antibody ELISA. We applied mixed models to investigate the intervention effect and predictors of serum levels while considering the repeated measurement design. Adherence with the study regimen was high and dropout rates were acceptable. Randomisation resulted in similar mean IGF-1 and IGFBP-3 levels by group. We did not observe a significant intervention effect on IGF-1, IGFBP-3, and their molar ratio during the entire study period. However, urinary isoflavone excretion during the study period was positively associated with IGF-1 (P=0.04) and the IGF-1:IGFBP-3 ratio (P=0.06). The effect was consistent over time. Adding soya foods to the diet of premenopausal women does not appear to lower serum levels of IGF-1 and IGFBP-3; if anything, the greater protein intake from soya may lead to a small increase in IGF-1 serum levels.","title":"Insulin-like growth factor-1 and binding protein-3 in a 2-year soya intervention among premenopausal women."},{"docid":"MED-3245","text":"Cruciferous vegetables, tomato sauce, and legumes have been associated with reduced risk of incident advanced prostate cancer. In vitro and animal studies suggest these foods may inhibit progression of prostate cancer, but there are limited data in men. Therefore, we prospectively examined whether intake of total vegetables, and specifically cruciferous vegetables, tomato sauce, and legumes, after diagnosis reduce risk of prostate cancer progression among 1,560 men diagnosed with non-metastatic prostate cancer and participating in the Cancer of the Prostate Strategic Urologic Research Endeavor, a United States prostate cancer registry. As a secondary analysis, we also examined other vegetable sub-groups, total fruit, and subgroups of fruits. The participants were diagnosed primarily at community-based clinics and followed from 2004–2009. We assessed vegetable and fruit intake via a semi-quantitative food frequency questionnaire, and ascertained prostate cancer outcomes via urologist report and medical records. We observed 134 events of progression (53 biochemical recurrences, 71 secondary treatments likely due to recurrence, six bone metastases, four prostate cancer deaths) during 3,171 person-yrs. Men in the fourth quartile of post-diagnostic cruciferous vegetable intake had a statistically significant 59% decreased risk of prostate cancer progression compared to men in the lowest quartile (hazard ratio (HR): 0.41; 95% confidence interval (CI): 0.22, 0.76; p-trend: 0.003). No other vegetable or fruit group was statistically significantly associated with risk of prostate cancer progression. In conclusion, cruciferous vegetable intake after diagnosis may reduce risk of prostate cancer progression.","title":"Vegetable and fruit intake after diagnosis and risk of prostate cancer progression"},{"docid":"MED-1723","text":"The lower rates of some cancers in Asian countries than in Western countries may be partly because of diet, although the mechanisms are unknown. The aim of this cross-sectional study was to determine whether a plant-based (vegan) diet is associated with a lower circulating level of insulin-like growth factor I (IGF-I) compared with a meat-eating or lacto-ovo-vegetarian diet among 292 British women, ages 20-70 years. The mean serum IGF-I concentration was 13% lower in 92 vegan women compared with 99 meat-eaters and 101 vegetarians (P = 0.0006). The mean concentrations of both serum IGF-binding protein (IGFBP)-1 and IGFBP-2 were 20-40% higher in vegan women compared with meat-eaters and vegetarians (P = 0.005 and P = 0.0008 for IGFBP-1 and IGFBP-2, respectively). There were no significant differences in IGFBP-3, C-peptide, or sex hormone-binding globulin concentrations between the diet groups. Intake of protein rich in essential amino acids was positively associated with serum IGF-I (Pearson partial correlation coefficient; r = 0.27; P < 0.0001) and explained most of the differences in IGF-I concentration between the diet groups. These data suggest that a plant-based diet is associated with lower circulating levels of total IGF-I and higher levels of IGFBP-1 and IGFBP-2.","title":"The associations of diet with serum insulin-like growth factor I and its main binding proteins in 292 women meat-eaters, vegetarians, and vegans."},{"docid":"MED-4053","text":"Heterocyclic amines (HCAs), potent mutagens and a risk factor for human cancers, are produced in meats cooked at high temperature. The aim of this study was to determine the HCA content in cooked meat products (beef, chicken, pork, fish) prepared by various cooking methods (pan frying, oven broiling, and oven baking at 170 to 230°C) that are preferred by U.S. meat consumers. The primary HCAs in these samples were PhIP (2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine) (1.49-10.89ng/g), MeIQx (2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline) (not detected-4.0ng/g), and DiMeIQx (2-amino-3,4,8-trimethyl-imidazo [4,5-f]quinoxaline) (not detected-3.57ng/g). Type and content of HCAs in cooked meat samples were highly dependent on cooking conditions. The total HCA content in well-done meat was 3.5 times higher than that of medium-rare meat. Fried pork (13.91ng/g) had higher levels of total HCAs than fried beef (8.92ng/g) and fried chicken (7.00ng/g). Among the samples, fried bacon contained the highest total HCA content (17.59ng/g). Copyright © 2011 Elsevier Ltd. All rights reserved.","title":"Occurrence of heterocyclic amines in cooked meat products."},{"docid":"MED-2450","text":"Background Atopy is not uncommon among children living in rural Crete, but wheeze and rhinitis are rare. A study was undertaken to examine whether this discrepancy could be attributed to a high consumption of fresh fruit and vegetables or adherence to a traditional Mediterranean diet. Methods A cross‐sectional survey was performed in 690 children aged 7–18 years in rural Crete. Parents completed a questionnaire on their child's respiratory and allergic symptoms and a 58‐item food frequency questionnaire. Adherence to a Mediterranean diet was measured using a scale with 12 dietary items. Children underwent skin prick tests with 10 common aeroallergens. Results 80% of children ate fresh fruit (and 68% vegetables) at least twice a day. The intake of grapes, oranges, apples, and fresh tomatoes—the main local products in Crete—had no association with atopy but was protective for wheezing and rhinitis. A high consumption of nuts was found to be inversely associated with wheezing (OR 0.46; 95% CI 0.20 to 0.98), whereas margarine increased the risk of both wheeze (OR 2.19; 95% CI 1.01 to 4.82) and allergic rhinitis (OR 2.10; 95% CI 1.31 to 3.37). A high level of adherence to the Mediterranean diet was protective for allergic rhinitis (OR 0.34; 95% CI 0.18 to 0.64) while a more modest protection was observed for wheezing and atopy. Conclusion The results of this study suggest a beneficial effect of commonly consumed fruits, vegetables and nuts, and of a high adherence to a traditional Mediterranean diet during childhood on symptoms of asthma and rhinitis. Diet may explain the relative lack of allergic symptoms in this population.","title":"Protective effect of fruits, vegetables and the Mediterranean diet on asthma and allergies among children in Crete"},{"docid":"MED-2295","text":"BACKGROUND: Intake of dietary fiber has been recommended for many years as part of the guidelines from the American Heart Association, the Institute of Medicine, and other groups. The recommended Adequate Intake for dietary fiber for adults is 25 to 38 g/day (14 g/1,000 kcal/day). OBJECTIVE: To determine the average daily intake of dietary fiber among adults during the past decade and, specifically, to document progress toward national goals. DESIGN: Cross-sectional weighted data from the National Health and Nutrition Examination Survey among adults aged 18 years and older. PARTICIPANTS/SETTING: Data were collected from noninstitutionalized adults aged 18 years and older using a nationally representative, complex, multistage, probability-based survey of people living in the United States that was conducted by the National Center for Health Statistics. MAIN OUTCOME MEASURES: Daily dietary fiber intake by members of the US population based on 2-year groupings of the continuous survey from 1999 to 2008. RESULTS: Mean daily dietary fiber intake for 1999-2000 was 15.6 g/day, for 2001-2002 intake was 16.1g/day, for 2003-2004 intake was 15.5 g/day, for 2005-2006 intake was 15.8 g/day, and for 2007-2008 intake was 15.9 g/day. Participants with obesity (body mass index ≥30) consistently reported lower fiber intake than did individuals with normal weight or overweight (14.6 to 15.4 g/day and 15.6 to 16.8 g/day, respectively; P<0.0001). Mexican Americans had significantly higher intake in 1999-2000 than non-Hispanic whites (18.0 vs 16.1g/day; P<0.05), but Mexican Americans' intake did not increase over time (17.7 g/day in 2007-2008). Non-Hispanic blacks had fiber intake of 12.5 g/day at baseline that increased modestly to 13.1 g/day by 2007-2008. CONCLUSIONS: Daily fiber intake generally has not progressed toward national goals during the past decade, but there are some differences according to health and social factors. Additional clinical practice and public health strategies are needed. Copyright © 2012 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.","title":"Trends in dietary fiber intake in the United States, 1999-2008."},{"docid":"MED-4305","text":"Influence of diet composition on mood during weight-reducing diets was studied in healthy young women of normal weight. A broad range of macronutrient intake was achieved by means of divergent dietary instructions for the composition of a 1,000 kcal per day diet adhered to for six weeks. Global mood during the last three weeks of the diet was significantly better in the \"vegetarian\" than in the \"mixed\" diet group. During this time a significant correlation was observed between relative carbohydrate intake and global mood (r = -0.74; p less than 0.01) and between the ratio of plasma tryptophan to other large neutral amino acids (a predictor of tryptophan flow into brain) and global mood (r = -0.52; p less than 0.05). Results suggest that group differences are related to differences in carbohydrate intake. It is hypothesized that impairment of central serotonergic function due to reduced tryptophan availability can prompt mood deterioration in situations of relatively low carbohydrate intake.","title":"Macronutrient intake, plasma large neutral amino acids and mood during weight-reducing diets."},{"docid":"MED-2658","text":"The prevalence of allergic diseases has increased in recent decades. Allergic diseases, particularly asthma, are complex diseases with strong gene-environment interactions. Epidemiological studies have identified a variety of risk factors for the development of allergic diseases. Among them, endocrine-disrupting chemicals (EDCs) play an important role in triggering or exacerbating these diseases. 4-Nonylphenol (NP) and 4-octylphenol (OP)--two major alkylphenols--have been recognized as common toxic and xenobiotic endocrine disrupters. Due to their low solubility, high hydrophobicity, and low estrogenic activity, they tend to accumulate in the human body and may be associated with the adverse effects of allergic diseases. Recently, new evidence has supported the importance of alkylphenols in the in vitro allergic response. This review focuses on the effects of alkylphenols on several key cell types in the context of allergic inflammation. Copyright © 2012. Published by Elsevier B.V.","title":"Alkylphenols--potential modulators of the allergic response."},{"docid":"MED-2511","text":"Residents of Okinawa, the southernmost prefecture of Japan, are known for their long average life expectancy, high numbers of centenarians, and accompanying low risk of age-associated diseases. Much of the longevity advantage in Okinawa is thought to be related to a healthy lifestyle, particularly the traditional diet, which is low in calories yet nutritionally dense, especially with regard to phytonutrients in the form of antioxidants and flavonoids. Research suggests that diets associated with a reduced risk of chronic diseases are similar to the traditional Okinawan diet, that is, vegetable and fruit heavy (therefore phytonutrient and antioxidant rich) but reduced in meat, refined grains, saturated fat, sugar, salt, and full-fat dairy products. Many of the characteristics of the diet in Okinawa are shared with other healthy dietary patterns, such as the traditional Mediterranean diet or the modern DASH (Dietary Approaches to Stop Hypertension) diet. Features such as the low levels of saturated fat, high antioxidant intake, and low glycemic load in these diets are likely contributing to a decreased risk for cardiovascular disease, some cancers, and other chronic diseases through multiple mechanisms, including reduced oxidative stress. A comparison of the nutrient profiles of the three dietary patterns shows that the traditional Okinawan diet is the lowest in fat intake, particularly in terms of saturated fat, and highest in carbohydrate intake, in keeping with the very high intake of antioxidant-rich yet calorie-poor orange-yellow root vegetables, such as sweet potatoes, and green leafy vegetables. Deeper analyses of the individual components of the Okinawan diet reveal that many of the traditional foods, herbs, or spices consumed on a regular basis could be labeled \"functional foods\" and, indeed, are currently being explored for their potential health-enhancing properties.","title":"The Okinawan diet: health implications of a low-calorie, nutrient-dense, antioxidant-rich dietary pattern low in glycemic load."},{"docid":"MED-1714","text":"BACKGROUND: Western diets, obesity, and sedentary lifestyles are associated with increased cancer risk. The mechanisms responsible for this increased risk, however, are not clear. OBJECTIVE: We hypothesized that long-term low protein, low calorie intake and endurance exercise are associated with low concentrations of plasma growth factors and hormones that are linked to an increased risk of cancer. DESIGN: Plasma growth factors and hormones were evaluated in 21 sedentary subjects, who had been eating a low-protein, low-calorie diet for 4.4 +/- 2.8 y (x +/- SD age: 53.0 +/- 11 y); 21 endurance runners matched by body mass index (BMI; in kg/m2); and 21 age- and sex-matched sedentary subjects eating Western diets. RESULTS: BMI was lower in the low-protein, low-calorie diet (21.3 +/- 3.1) and runner (21.6 +/- 1.6) groups than in the Western diet (26.5 +/- 2.7; P < 0.005) group. Plasma concentrations of insulin, free sex hormones, leptin, and C-reactive protein were lower and sex hormone-binding globulin was higher in the low-protein, low-calorie diet and runner groups than in the sedentary Western diet group (all P < 0.05). Plasma insulin-like growth factor I (IGF-I) and the concentration ratio of IGF-I to IGF binding protein 3 were lower in the low-protein, low-calorie diet group (139 +/- 37 ng/mL and 0.033 +/- 0.01, respectively) than in the runner (177 +/- 37 ng/mL and 0.044 +/- 0.01, respectively) and sedentary Western (201 +/- 42 ng/mL and 0.046 +/- 0.01, respectively) diet groups (P < 0.005). CONCLUSIONS: Exercise training, decreased adiposity, and long-term consumption of a low-protein, low-calorie diet are associated with low plasma growth factors and hormones that are linked to an increased risk of cancer. Low protein intake may have additional protective effects because it is associated with a decrease in circulating IGF-I independent of body fat mass.","title":"Long-term low-protein, low-calorie diet and endurance exercise modulate metabolic factors associated with cancer risk."},{"docid":"MED-3929","text":"Objective: To prospectively examine whether higher intakes of total flavonoids and their subclasses (flavanones, anthocyanins, flavan-3-ols, flavonols, flavones, and polymers) were associated with a lower risk of developing Parkinson disease (PD). Methods: In the current analysis, we included 49,281 men in the Health Professional Follow-up Study and 80,336 women from the Nurses' Health Study. Five major sources of flavonoid-rich foods (tea, berry fruits, apples, red wine, and orange/orange juice) were also examined. Flavonoid intake was assessed using an updated food composition database and a validated food frequency questionnaire. Results: We identified 805 participants (438 men and 367 women) who developed PD during 20–22 years of follow-up. In men, after adjusting for multiple confounders, participants in the highest quintile of total flavonoids had a 40%lower PD risk than those in the lowest quintile (hazard ratio [HR] = 0.60; 95% confidence interval 0.43, 0.83; p trend = 0.001). No significant relationship was observed in women (p trend = 0.62) or in pooled analyses (p trend = 0.23). In the pooled analyses for the subclasses, intakes of anthocyanins and a rich dietary source, berries, were significantly associated with a lower PD risk (HR comparing 2 extreme intake quintiles were 0.76 for anthocyanins and 0.77 for berries, respectively; p trend < 0.02 for both). Conclusions: Our findings suggest that intake of some flavonoids may reduce PD risk, particularly in men, but a protective effect of other constituents of plant foods cannot be excluded.","title":"Habitual intake of dietary flavonoids and risk of Parkinson disease"},{"docid":"MED-2278","text":"OBJECTIVES: To investigate the anti-inflammatory and anti-oxidative effects of anthocyanins from cherries on Freund's adjuvant-induced arthritis (AIA) in rats. METHODS: Arthritis was induced intradermally by injection with 0.1 mL of complete Freund's adjuvant (CFA) into the right hind footpad of male Sprague Dawley (SD) rats. Anthocyanins at 40, 20 and 10 mg/kg (body weight) were administered orally to the treated rats for 28 days after the injection. Tumour necrosis factor-alpha (TNFalpha) in serum and prostaglandin E2 (PGE2) in paws were assayed by radioimmunoassay (RIA), and anti-oxidative effects was assayed by measuring total anti-oxidative capacity (T-AOC), superoxide dismutase (SOD) and malondialdehyde (MDA) in serum. RESULTS: Anthocyanins at 40 mg/kg significantly decreased the levels of TNFalpha in serum and PGE2 in paws, simultaneously improving the anti-oxidative status of AIA. We found that at this dosage T-AOC was potentized, the activity of SOD increased and the level of MDA in serum decreased. However, anthocyanins at 20 and 10 mg/kg had less effect on the inflammatory factors and anti-oxidative capacity of AIA. CONCLUSIONS: Anthocyanins have potential anti-inflammatory and anti-oxidative effects on AIA.","title":"Anti-inflammatory and anti-oxidative effects of cherries on Freund's adjuvant-induced arthritis in rats."},{"docid":"MED-1616","text":"The role of very-low-carbohydrate ketogenic diets (VLCKD) in the long-term management of obesity is not well established. The present meta-analysis aimed to investigate whether individuals assigned to a VLCKD (i.e. a diet with no more than 50 g carbohydrates/d) achieve better long-term body weight and cardiovascular risk factor management when compared with individuals assigned to a conventional low-fat diet (LFD; i.e. a restricted-energy diet with less than 30% of energy from fat). Through August 2012, MEDLINE, CENTRAL, ScienceDirect,Scopus, LILACS, SciELO, ClinicalTrials.gov and grey literature databases were searched, using no date or language restrictions, for randomised controlled trials that assigned adults to a VLCKD or a LFD, with 12 months or more of follow-up. The primary outcome was bodyweight. The secondary outcomes were TAG, HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), systolic and diastolic blood pressure,glucose, insulin, HbA1c and C-reactive protein levels. A total of thirteen studies met the inclusion/exclusion criteria. In the overall analysis,five outcomes revealed significant results. Individuals assigned to a VLCKD showed decreased body weight (weighted mean difference 20·91 (95% CI 21·65, 20·17) kg, 1415 patients), TAG (weighted mean difference 20·18 (95% CI 20·27, 20·08) mmol/l, 1258 patients)and diastolic blood pressure (weighted mean difference 21·43 (95% CI 22·49, 20·37) mmHg, 1298 patients) while increased HDL-C(weighted mean difference 0·09 (95% CI 0·06, 0·12) mmol/l, 1257 patients) and LDL-C (weighted mean difference 0·12 (95% CI 0·04,0·2) mmol/l, 1255 patients). Individuals assigned to a VLCKD achieve a greater weight loss than those assigned to a LFD in the longterm; hence, a VLCKD may be an alternative tool against obesity.","title":"Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss: a meta-analysis of randomised controlled trials."},{"docid":"MED-4556","text":"Tolerable upper intake levels (ULs) set by the Institute of Medicine (IOM) are important, in part because they are used for estimating the percentage of the population at potential risk of adverse effects from excessive nutrient intake. The IOM did not set ULs for trans fat, saturated fat, and cholesterol because any intake level above 0% of energy increased LDL cholesterol concentration and these three food components are unavoidable in ordinary diets. The purpose of the analysis presented in this review was to evaluate clinical trial and prospective observational data that were not previously considered for setting a UL with the aim of determining whether the current UL model could be used for saturated fat, trans fat, and cholesterol. The results of this analysis confirm the limitations of the risk assessment model for setting ULs because of its inability to identify a UL for food components, such as cholesterol, that lack an intake threshold associated with increased chronic disease risk. © 2011 International Life Sciences Institute.","title":"Tolerable upper intake levels for trans fat, saturated fat, and cholesterol."},{"docid":"MED-2461","text":"This study aimed to evaluate the association of diet with respiratory symptoms and asthma in schoolchildren in Taipei, Taiwan. An in-class interview survey elicited experiences of asthma and respiratory symptoms and consumption frequencies of the major food categories in 2290 fifth graders. Respiratory symptoms surveyed included persistent cough, chest tightness, wheezing with cold, wheezing without cold, dyspnea-associated wheezing, and exercise-induced cough or wheezing. Results showed that the consumption of sweetened beverages had the strongest association with respiratory symptoms and was positively associated with six of the seven respiratory symptoms (all p < 0.05). The adjusted odds ratios (aOR) ranged from 1.05 (95% confidence interval (CI = 1.01-1.09) for exercise-induced cough to 1.09 (95% CI = 1.03-1.16) for wheezing without cold. Egg consumption was associated with 5 of the 7 respiratory symptoms. Consumptions of seafood, soy products, and fruits were each negatively associated with one of the seven respiratory symptoms (all p < 0.05). Consumption of seafood was negatively associated with physician-diagnosed asthma and consumptions of sweetened beverages and eggs were positively associated with suspected asthma (p < 0.05). In conclusion, the study suggests that diet is associated with the respiratory symptoms in schoolchildren in Taipei. Consumptions of sweetened beverages and eggs are associated with increased risk of respiratory symptoms and asthma whereas consumptions of soy products and fruits are associated with reduced risk of respiratory symptoms.","title":"The association of diet with respiratory symptoms and asthma in schoolchildren in Taipei, Taiwan."},{"docid":"MED-2591","text":"Low-carbohydrate diets have become increasingly popular for weight loss. Although they may improve some metabolic markers, particularly in type 2 diabetes mellitus (T2D) or the metabolic syndrome (MS), their net effect on arterial wall function remains unclear. The objective was to evaluate the relation between dietary macronutrient composition and the small artery reactive hyperaemia index (saRHI), a marker of small artery endothelial function, in a cohort of patients at increased cardiovascular (CV) risk. The present cross-sectional study included 247 patients. Diet was evaluated by a 3-d food-intake register and reduced to a novel low-carbohydrate diet score (LCDS). Physical examination, demographic, biochemical and anthropometry parameters were recorded, and the saRHI was measured in each patient. Individuals in the lowest LCDS quartile (Q1, 45 % carbohydrate; 20 % protein; 32 % fat) had higher saRHI values than those in the top quartile (Q4, 29 % carbohydrate, 24 % protein, 40 % fat; 1.66 (sd 0.41) v. 1.52 (sd 0.22), P= 0.037). These results were particularly strong in patients with the MS (Q1 = 1.82 (sd 0.32) v. Q4 = 1.61 (sd 027); P= 0.021) and T2D (Q1 = 1.78 (sd 0.31) v. Q4 = 1.62 (sd 0.35); P= 0.011). Multivariate analysis demonstrated that individuals in the highest LCDS quartile had a significantly negative coefficient of saRHI, which was independent of confounders (OR -0.85; 95 % CI 0.19, 0.92; P= 0.031). These findings suggest that a dietary pattern characterised by a low amount of carbohydrate, but high amounts of protein and fat, is associated with a poorer small artery vascular reactivity in patients with increased CV risk.","title":"Negative effect of a low-carbohydrate, high-protein, high-fat diet on small peripheral artery reactivity in patients with increased cardiovascular ..."},{"docid":"MED-1184","text":"It has been shown that feces of patients with ulcerative colitis uniformly contain sulfate reducing bacteria. Sulfide produced by these bacteria interferes with butyrate-dependent energy metabolism of cultured colonocytes and may be involved in the pathogenesis of ulcerative colitis. Mucosal biopsies from the sigmoid rectum of 10 patients (no caner, polyps, inflammatory bowel disease) were incubated with either NaCl, sodium hydrogen sulfide (1 mmol/L), a combination of both sodium hydrogen sulfide and butyrate (10 mmol/L), or butyrate. Mucosal proliferation was assessed by bromodeoxyuridine labeling of cells in S-phase. Compared to NaCl, sulfide increased the labeling of the entire crypt significantly, by 19% (p < 0.05). This effect was due to an expansion of the proliferative zone to the upper crypt (compartments 3-5), where the increase in proliferation was 54%. Sulfide-induced hyperproliferation was reversed when samples were coincubated with sulfide and butyrate. The study shows that sodium hydrogen sulfide induces mucosal hyperproliferation. Our data support a possible role of sulfide in the pathogenesis of UC and confirm the role of butyrate in the regulation of colonic proliferation and in the treatment of UC.","title":"Antagonistic effects of sulfide and butyrate on proliferation of colonic mucosa: a potential role for these agents in the pathogenesis of ulcerativ..."},{"docid":"MED-4976","text":"Airborne cooking by-products from frying beef (hamburgers), pork (bacon strips) and soybean-based food (tempeh burgers) were collected, extracted, tested for mutagenicity and chemically analysed. The fumes generated by frying pork and beef were mutagenic, with 4900 and 1300 revertants/g of food cooked, respectively. No mutagenicity was detected in fumes from frying tempeh burgers. Bacon fried to a well-done but non-charred state was eight times more mutagenic in a microsuspension Ames/Salmonella test (TA98 with S-9) than hamburgers and about 350 times more mutagenic than tempeh burgers. Among food samples cooked to a well-done, non-charred state, bacon strips had almost 15-fold more mass (109.5 ng/g) than that of the beef, whereas no heterocyclic amine (HCA) was detected in the fried tempeh burgers. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was the most abundant HCA, followed by 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx). No 2-amino-9H-pyrido[2,3-b]indole (A alpha C) was detected in the food samples fried at about 200 degrees C, although it was present in the collected airborne products. The total amounts of HCAs in the smoke condensates were 3 ng/g from fried bacon, 0.37 ng/g from fried beef and 0.177 ng/g from fried soy-based food. This study indicates that cooks are potentially exposed to relatively high levels of airborne mutagens and carcinogens and that long-term sampling inside restaurants and kitchens may be warranted in order to assess the potential risk of prolonged exposure.","title":"Airborne mutagens produced by frying beef, pork and a soy-based food."},{"docid":"MED-4216","text":"High levels of insulin-like growth factor 1 (IGF-1) are associated with increased risk of prostate cancer, whereas increased levels of some of its binding proteins (IGFBPs) seem to be protective. High intakes of dietary protein, especially animal and soy protein, appear to increase IGF-1. However, soy isoflavones have demonstrated anti-proliferative and apoptotic effects both in vitro and in vivo. We evaluated dietary intakes of total protein and soy isoflavones in relation to the IGF axis in prostate cancer patients making comprehensive lifestyle changes including a very low-fat vegan diet supplemented with soy protein (58 g/day). After one year, intervention group patients reported significantly higher intakes of dietary protein and soy isoflavones compared to usual-care controls (P < 0.001). IGF-1 increased significantly in both groups, whereas IGFBP-1 rose in the experimental group only (P < 0.01). Increases in vegetable protein over one year were associated with increases in IGFBP-1 among intervention group patients (P < 0.05). These results suggest that dietary protein and soy isoflavones, in the context of comprehensive lifestyle changes, may not significantly alter IGF-1. However, given the recent literature indicating that high intake of protein rich in essential amino acids (animal or soy protein) may increase IGF-1, it may be prudent for men with early stage prostate cancer not to exceed dietary protein recommendations.","title":"Relationship of dietary protein and soy isoflavones to serum IGF-1 and IGF binding proteins in the Prostate Cancer Lifestyle Trial."},{"docid":"MED-4600","text":"Enough solid evidence now exists to offer women several fundamental strategies for healthy eating. They include emphasizing healthful unsaturated fats, whole grains, good protein “packages,” and fruits and vegetables; limiting consumption of trans and saturated fats, highly refined grains, and sugary beverages; and taking a multivitamin with folic acid and extra vitamin D as a nutritional safety net. A diet based on these principles is healthy through virtually all life stages, from young adulthood through planning for pregnancy, pregnancy, and on into old age.","title":"Essentials of Healthy Eating: A Guide"},{"docid":"MED-3001","text":"Over the last three decades, the concept of Western disease has become well established. Medicine has approached this group of diseases by searching for new cures but has achieved relatively little success. We argue that medicine should now accept the failure of this strategy and place a major emphasis on prevention. The key objective is to change the climate of opinion so that prevention is taken seriously by the general population. The chief activity should be a wide ranging public education campaign so as to persuade people to live a healthier lifestyle. Medicine will require restructuring in order to carry out this work. Medical education needs to be reformed so that medical students receive the necessary training. This must be done as part of an integrated approach in which government, industry and medical research all play a major role. Governments should use taxation and subsidies in areas such as food and tobacco so as to shift consumption patterns towards healthier products. Governments must also tighten laws on tobacco sales and advertising, support health education, and improve food labelling. Industry must be made far more responsive to the health needs of the population. This should be done both by public education, so as to alter demand, and by government action. Medical research should change its emphasis from studying the detailed mechanisms of disease (\"complex research\") to studying the role of lifestyle factors (\"simple research\").","title":"Towards a new system of health: the challenge of Western disease."},{"docid":"MED-2202","text":"The overall objective of this chapter is to review the past, present, and future role of the sweet potato (Ipomoea batatas [L.] Lam) in human nutrition. Specifically, the chapter describes the role of the sweet potato in human diets; outlines the biochemical and nutritional composition of the sweet potato with emphasis on its beta-carotene and anthocyanin contents; highlights sweet potato utilization, and its potential as value-added products in human food systems; and demonstrates the potential of the sweet potato in the African context. Early records have indicated that the sweet potato is a staple food source for many indigenous populations in Central and South Americas, Ryukyu Island, Africa, the Caribbean, the Maori people, Hawaiians, and Papua New Guineans. Protein contents of sweet potato leaves and roots range from 4.0% to 27.0% and 1.0% to 9.0%, respectively. The sweet potato could be considered as an excellent novel source of natural health-promoting compounds, such as beta-carotene and anthocyanins, for the functional food market. Also, the high concentration of anthocyanin and beta-carotene in sweet potato, combined with the high stability of the color extract make it a promising and healthier alternative to synthetic coloring agents in food systems. Starch and flour processing from sweet potato can create new economic and employment activities for farmers and rural households, and can add nutritional value to food systems. Repositioning sweet potato production and its potential for value-added products will contribute substantially to utilizing its benefits and many uses in human food systems. Multidisciplinary, integrated research and development activities aimed at improving production, storage, postharvest and processing technologies, and quality of the sweet potato and its potential value-added products are critical issues, which should be addressed globally.","title":"Sweet potato: a review of its past, present, and future role in human nutrition."},{"docid":"MED-1612","text":"Type II diabetic subjects were given 50 g protein, 50 g glucose, or 50 g glucose with 50 g protein as a single meal in random sequence. The plasma glucose and insulin response was determined over the subsequent 5 h. The plasma glucose area above the baseline following a glucose meal was reduced 34% when protein was given with the glucose. When protein was given alone, the glucose concentration remained stable for 2 h and then declined. The insulin area following glucose was only modestly greater than with a protein meal (97 +/- 35, 83 +/- 19 microU X h/ml, respectively). When glucose was given with protein, the mean insulin area was considerably greater than when glucose or protein was given alone (247 +/- 33 microU X h/ml). When various amounts of protein were given with 50 g glucose, the insulin area response was essentially first order. Subsequently, subjects were given 50 g glucose or 50 g glucose with 50 g protein as two meals 4 h apart in random sequence. The insulin areas were not significantly different for each meal but were higher when protein + glucose was given. After the second glucose meal the plasma glucose area was 33% less than after the first meal. Following the second glucose + protein meal the plasma glucose area was markedly reduced, being only 7% as large as after the first meal. These data indicate that protein given with glucose will increase insulin secretion and reduce the plasma glucose rise in at least some type II diabetic persons.","title":"Effect of protein ingestion on the glucose and insulin response to a standardized oral glucose load."},{"docid":"MED-2505","text":"BACKGROUND: Relative risk estimates suggest that effective implementation of behaviors commonly advocated in preventive medicine should increase life expectancy, although there is little direct evidence. OBJECTIVE: To test the hypothesis that choices regarding diet, exercise, and smoking influence life expectancy. METHODS: A total of 34 192 California Seventh-Day Adventists (75% of those eligible) were enrolled in a cohort and followed up from 1976 to 1988. A mailed questionnaire provided dietary and other exposure information at study baseline. Mortality for all subjects was ascertained by matching to state death tapes and the National Death Index. RESULTS: California Adventists have higher life expectancies at the age of 30 years than other white Californians by 7.28 years (95% confidence interval, 6.59-7.97 years) in men and by 4.42 years (95% confidence interval, 3.96-4.88 years) in women, giving them perhaps the highest life expectancy of any formally described population. Commonly observed combinations of diet, exercise, body mass index, past smoking habits, and hormone replacement therapy (in women) can account for differences of up to 10 years of life expectancy among Adventists. A comparison of life expectancy when these factors take high-risk compared with low-risk values shows independent effects that vary between 1.06 and 2.74 years for different variables. The effect of each variable is assessed with all others at either medium- or high-risk levels. CONCLUSIONS: Choices regarding diet, exercise, cigarette smoking, body weight, and hormone replacement therapy, in combination, appear to change life expectancy by many years. The longevity experience of Adventists probably demonstrates the beneficial effects of more optimal behaviors.","title":"Ten years of life: Is it a matter of choice?"},{"docid":"MED-3305","text":"BACKGROUND AND AIM: The occurrence of malignant pleural mesothelioma (MPM) has been reported among population groups with no documented professional exposure to asbestos fibres living in different geographic areas. This paper reviews existing data related to non occupational MPM including its occurrence in the province of Catania (Sicily, Italy). METHODS: An electronic search of literature related to non occupational MPM was performed including the year 2005. RESULTS: Non occupational MPM in subjects living in areas contaminated by a variety of asbestos and non asbestos fibres has been well documented through a number of epidemiologic studies including cases series, case-control studies, and a cohort study. In addition, the observation of familial clustering of MPM, suggests that genetic factors may play a role in the pathogenesis of this malignancy. The epidemiological evidence also suggests that MPM may occur as a result of the interaction between environmental carcinogens, genetic factors, and virus infection. CONCLUSION: It is likely that genetic predisposition and non-occupational exposure to low doses of asbestos and asbestos-like fibres may concur to the development of malignant mesothelioma. However, additional epidemiological and laboratory studies are needed to further understand the relationship between environmental exposure and individual susceptibility to this malignancy.","title":"Non-occupational malignant pleural mesothelioma due to asbestos and non-asbestos fibres."},{"docid":"MED-3454","text":"To determine if 6 weeks of supplementation with antioxidants could alleviate exercise-induced DNA damage, we studied 21 runners during a 50 km ultramarathon. Subjects were randomly assigned to one of two groups: (1) placebos (PL) or (2) antioxidants (AO) (1000 mg vitamin C and 400 IU RRR-alpha-tocopheryl acetate). The comet assay was used to assess DNA damage in circulating leukocytes at selected time points: pre-, mid-, and 2 h postrace and daily for 6 days postrace. All subjects completed the race: run time 7.1 +/- 0.1 h, energy expenditure 5008 +/- 80 kcal for women (n = 10) and 6932 +/- 206 kcal for men (n = 11). Overall, the percentage DNA damage increased at midrace (p <.02), but returned to baseline by 2 h postrace, indicating that the exercise bout induced nonpersistent DNA damage. There was a gender x treatment x time interaction (p <.01). One day postrace, women taking AO had 62% less DNA damage than women taking PL (p <.0008). In contrast, there were no statistically significant differences between the two treatment groups of men at any time point. Thus, endurance exercise resulted in DNA damage as shown by the comet assay and AO seemed to enhance recovery in women but not in men.","title":"Endurance exercise results in DNA damage as detected by the comet assay."},{"docid":"MED-3783","text":"Fish odour syndrome (trimethylaminuria) is a metabolic syndrome caused by abnormal excretion of trimethylamine in the breath, urine, sweat, saliva and vaginal secretions. Trimethylamine is derived from the intestinal bacterial degradation of foods rich in choline and carnitine and is normally oxidised by the liver to odourless trimethylamine N-oxide which is then excreted in the urine. Impaired oxidation of trimethylamine is thought to be the cause of the fish odour syndrome and is responsible for the smell of rotting fish. Certain foods rich in choline exacerbate the condition and the patients have a variety of psychological problems. Recognition of the condition is important as dietary adjustments reduce the excretion of trimethylamine and may reduce the odour. Occasionally, a short course of metronidazole, neomycin and lactulose may suppress production of trimethylamine by reducing the activity of gut microflora. Keywords: fish odour syndrome; trimethylaminuria","title":"Fish odour syndrome"},{"docid":"MED-4055","text":"Heterocyclic amines (HCAs) are formed when meat products such as beef, chicken, pork and fish are cooked at high temperatures. The most abundant HCA found in the human diet is 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP). PhIP causes mammary carcinomas in female rats and mice, and is associated with an increased risk of developing colon, breast, and prostate cancer in humans. PhIP is metabolized by cytochrome P-450s producing N-OH-PhIP. The N-OH-PhIP can be esterified by phase II enzymes forming an arylnitrenium ion that binds to DNA causing adducts. Furthermore, N-OH-PhIP may be reduced by cytochrome b5 reductase producing superoxide anions and hydroxyl radicals causing DNA strand breaks. Diallyl sulfide (DAS) has been shown to prevent cancer in several animal models, presumably by metabolic modulation. We hypothesize that PhIP produces reactive oxygen species causing DNA strand breaks and that DAS will inhibit the formation of PhIP induced DNA strand breaks. To test this hypothesis we treated normal breast epithelial (MCF-10A) cells with PhIP, DAS and a combination of PhIP and DAS. The detection of lipid peroxides was used as a surrogate for ROS. Lipid peroxides were detected using a PeroxiDetect kit (Sigma). PhIP increased the production of lipid peroxides and DAS decreased the PhIP-induced peroxidation by 47%. To determine if PhIP causes DNA strand breaks in MCF-10A cells, cells were treated for 3, 6, 9, and 24 h with PhIP (100 microM), DAS (100 microM) and a combination of PhIP (100 microM) and DAS (100 microM). DNA strand breaks were evaluated using the Comet assay. PhIP produced DNA strand breaks in a dose- and time-dependent fashion. We have shown that DAS inhibits PhIP-induced DNA strand breaks by inhibiting the production of reactive oxygen species. Therefore, we propose that DAS can prevent PhIP-induced breast cancer.","title":"Diallyl sulfide inhibits PhIP-induced DNA strand breaks in normal human breast epithelial cells."},{"docid":"MED-5186","text":"We evaluated the role of dietary nutrients in the etiology of endometrial cancer in a population-based case-control study of 1,204 newly diagnosed endometrial cancer cases and 1,212 age frequency-matched controls. Information on usual dietary habits was collected during an in-person interview using a validated, quantitative food frequency questionnaire. Logistic regression analysis was conducted to evaluate the association of nutrients with endometrial cancer risk using an energy density method (e.g., nutrient intake/1,000 kilocalories of intake). Higher energy intake was associated with increased risk, which was attributable to animal source energy and a high proportion of energy from protein and fat. Odds ratios comparing highest versus lowest quintiles of intake were elevated for intake of animal protein (Odds ratio (OR) 5 2.0, 95% confidential interval: 1.5–2.7) and fat (OR 5 1.5, 1.2–2.0), but reduced for plant sources of these nutrients (OR 5 0.7, 0.5–0.9 for protein and OR 5 0.6, 0.5–0.8 for fat). Further analysis showed that saturated and monounsaturated fat intake was associated with elevated risk, while polyunsaturated fat intake was unrelated to risk. Dietary retinol, β-carotene, vitamin C, vitamin E, fiber, and vitamin supplements were inversely associated with risk. No significant association was observed for dietary vitamin B1 or vitamin B2. Our findings suggest that associations of dietary macronutrients with endometrial cancer risk may depend on their sources, with intake of animal origin nutrients being related to higher risk and intake of plant origin nutrients related to lower risk. Dietary fiber, retinol, β-carotene, vitamin C, vitamin E, and vitamin supplementation may decrease the risk of endometrial cancer.","title":"Nutritional factors in relation to endometrial cancer: A report from a population-based case-control study in Shanghai, China"},{"docid":"MED-3193","text":"Background Multiple Myeloma (MM) is a B cell neoplasm causing lytic or osteopenic bone abnormalities. Whole body skeletal survey (WBSS), Magnetic resonance (MR) and 18F-FDG PET/CT are imaging techniques routinely used for the evaluation of bone involvement in MM patients. Aim As MM bone lesions may present low 18F-FDG uptake; the aim of this study was to assess the possible added value and limitations of 11C-Choline to that of 18F-FDG PET/CT in patients affected with MM. Methods Ten patients affected with MM underwent a standard 11C-Choline PET/CT and an 18F-FDG PET/CT within one week. The results of the two scans were compared in terms of number, sites and SUVmax of lesions. Results Four patients (40%) had a negative concordant 11C-Choline and 18F-FDG PET/CT scans. Two patients (20%) had a positive 11C-Choline and 18F-FDG PET/CT scans that identified the same number and sites of bone lesions. The remaining four patients (40%) had a positive 11C-Choline and 18F-FDG PET/CT scan, but the two exams identified different number of lesions. Choline showed a mean SUVmax of 5 while FDG showed a mean SUVmax of 3.8 (P = 0.042). Overall, 11C-Choline PET/CT scans detected 37 bone lesions and 18F-FDG PET/CT scans detected 22 bone lesions but the difference was not significant (P = 0.8). Conclusion According to these preliminary data, 11C-Choline PET/CT appears to be more sensitive than 18F-FDG PET/CT for the detection of bony myelomatous lesions. If these data are confirmed in larger series of patients, 11C-Choline may be considered a more appropriate functional imaging in association with MRI for MM bone staging.","title":"11C-choline vs. 18F-FDG PET/CT in assessing bone involvement in patients with multiple myeloma"},{"docid":"MED-2519","text":"To date, the only intervention that has consistently been shown to slow the rate of aging, and to increase mean and maximum lifespan in short-lived species, is life-long calorie restriction. It is yet unclear whether long-term calorie restriction in longer lived species (i.e. primates and humans) will have a similar effect. In humans, several studies investigating short-term calorie restriction or \"weight loss\" programs suggest beneficial outcomes on parameters of cardiovascular disease. Studies on long-term calorie restriction are performed on a self-selected group of human subjects and show similar effects. However, few studies are currently investigating the quality of life and potential pitfalls of long-term calorie restriction in humans. It is likely that some of the physiological and psychological effects of caloric restriction that occur in animals may impact the human life very differently. For certain, calorie restriction has a plethora of health benefits in mammals, such as a reduction in age-related diseases such as cancer. However, despite the \"magic\" of CR, this intervention in humans may present itself with a number of health concerns, which may not be applicable to or impact the life of experimental animals, but may do so in humans. These potential pitfalls and \"side effects\" are not clearly addressed in the literature and will be a focus of this review.","title":"Caloric restriction in humans: potential pitfalls and health concerns."},{"docid":"MED-2296","text":"This study aimed to investigate health belief as a major motive for diet and lifestyle behaviors of 100 vegans in the United States; and to determine congruence with selected health and nutrition outcomes. Response data from an administered questionnaire was analyzed. Statistical analyses determined the most common factors influencing diet choice; the number of vegans practicing particular lifestyle behaviors; body mass index; and prevalence of self-reported chronic disease diagnoses. Nutrient intakes were analyzed and assessed against Dietary Reference Intakes. Health was the most reported reason for diet choice (47%). In the health belief, animal welfare, and religious/other motive categories, low percentages of chronic disease diagnoses were reported: 27%, 11%, and 15%, respectively. There were no significant differences in health behaviors and indices among vegan motive categories, except for product fat content choices. Within the entire study population, health-related vegan motive coincided with regular exercise; 71% normal BMI (mean=22.6); minimal alcohol and smoking practices; frequently consumed vegetables, nuts, and grains; healthy choices in meal types, cooking methods, and low-fat product consumption; and adequate intakes for most protective nutrients when compared to reference values. But incongruence was found with 0% intake adequacy for vitamin D; and observation of excessive sodium use. Copyright © 2013 Elsevier Ltd. All rights reserved.","title":"Vegan lifestyle behaviors: an exploration of congruence with health-related beliefs and assessed health indices."},{"docid":"MED-2659","text":"U.S. and European regulators and researchers disagree over risks of a common class of surfactants.","title":"European bans on surfactant trigger transatlantic debate."},{"docid":"MED-3132","text":"Little is known about dietitians current practice in counselling clients about the use of legumes in a low fat, high fibre diet. An exploratory e-mail questionnaire was sent to members of Dietitians of Canada to assess: dietitian use and preferences for legumes, dietitian practice, opinions about clients attitudes and preferences, and resource needs. Counsellors (n=256) had high personal use of legumes (64% > or = 1 serving/week) and frequently recommended legumes in counselling. The legumes most preferred by respondents and their clients were: peanuts, kidney beans, split peas, chickpeas, and lentils. Respondents often recommended canned bean products (76%) and tofu (61%), but other legume grocery products were less often recommended. The most common client issues identified were: flatulence (87% agreed), lack of familiarity (85%), and knowledge of preparation (82%). Dietitians were not satisfied with current resources to support practice, especially those respondents providing primarily clinical counselling services. The most requested resources were: recipes (90%), pamphlets (82%), food demonstrations (75%) and Internet sites (63%). Client level research is now needed to confirm the importance of the issues identified and to develop and test strategies for legume promotion in counselling.","title":"Legume promotion in counselling: an e-mail survey of dietitians."},{"docid":"MED-2453","text":"BACKGROUND: Fresh fruit consumption and vitamin C intake have been associated with improved lung function in adults. Whether this is due to enhancement of lung growth, to a reduction in lung function decline, or to protection against bronchospasm is unclear. METHODS: In a cross- sectional school based survey of 2650 children aged 8-11 from 10 towns in England and Wales the main outcome measure was forced expiratory volume in one second (FEV1) standardised for body size and sex. Exposure was assessed by a food frequency questionnaire to parents and by measurement of plasma levels of vitamin C in a subsample of 278 children. RESULTS: FEV1 was positively associated with frequency of fresh fruit consumption. After adjustment for possible confounding variables including social class and passive smoking, those who never ate any fresh fruit had an estimated FEV1 some 79 ml (4.3%) lower than those who ate these items more than once a day (95% CI 22 to 136 ml). The association between FEV1 and fruit consumption was stronger in subjects with wheeze than in non-wheezers (p = 0.020 for difference in trend), though wheeze itself was not related to fresh fruit consumption. Frequency of consumption of salads and of green vegetables were both associated with FEV1 but the relationships were weaker than for fresh fruit. Plasma vitamin C levels were unrelated to FEV1 (r = - 0.01, p = 0.92) or to wheeze and were only weakly related to fresh fruit consumption (r = 0.13, p = 0.055). CONCLUSIONS: Fresh fruit consumption appears to have a beneficial effect on lung function in children. Further work is needed to confirm whether the effect is restricted to subjects who wheeze and to identify the specific nutrient involved.","title":"Effect of fresh fruit consumption on lung function and wheeze in children"},{"docid":"MED-2476","text":"An increase in asthma and atopic disease has been recorded in many countries where society has become more prosperous. We have investigated two possible explanations: a reduction in childhood infections and a change in diet. In a cohort of people followed up since 1964, originally selected as a random sample of primary school children, we have investigated the relevance of family size and the common childhood infectious diseases to development of eczema, hay fever and asthma. Although membership of a large family reduced risks of hay fever and eczema (but not asthma), this was not explained by the infections the child had suffered. Indeed, the more infections the child had had, the greater the likelihood of asthma, although measles gave a modest measure of protection. We have investigated dietary factors in two separate studies. In the first, we have shown the risks of bronchial hyper-reactivity are increased seven-fold among those with the lowest intake of vitamin C, while the lowest intake of saturated fats gave a 10-fold protection. In the second, we have shown that the risk of adult-onset wheezy illness is increased five-fold by the lowest intake of vitamin E and doubled by the lowest intake of vitamin C. These results were supported by direct measurements of the vitamins and triglycerides in plasma. We have proposed that changes in the diet of pregnant women may have reflected those observed in the population as a whole and that these may have resulted in the birth of cohorts of children predisposed to atopy and asthma. The direct test of this is to study the diet and nutritional status of a large cohort of pregnant women and to follow their offspring forward. This is our current research.","title":"Diet, infection and wheezy illness: lessons from adults."},{"docid":"MED-2475","text":"Current understanding of the use of exclusion diets in the management of asthma in children is limited and controversial. The aim of this study was to examine the effects of excluding eggs and milk on the occurrence of symptoms in children with asthma and involved 22 children aged between three and 14 years clinically diagnosed as having mild to moderate disease. The investigation was single blind and prospective, and parents were given the option of volunteering to join the 'experiment' group, avoiding eggs, milk and their products for eight weeks, or the 'control' group, who consumed their customary food. Thirteen children were recruited to the experimental group and nine to the control group. A trained paediatrician at the beginning and end of the study period assessed the children. A seven-day assessment of food intake was made before, during and immediately after the period of dietary intervention in both groups. A blood sample was taken from each child for determination of food specific antibodies and in those children who could do so, the peak expiratory flow rate (PEFR) was measured. Based on the recommended nutrient intake (RNI), the mean percentage energy intake of the children in the experimental group was significantly lower (p < 0.05) in the experimental group. After the eight-week study period and compared with baseline values, the mean serum anti-ovalbumin IgG and anti-beta lactoglobulin IgG concentrations were statistically significantly reduced (p < 0.05) for both in the experimental group. In contrast, the values for anti-ovalbumin IgG in the control group were significantly increased and those for anti-beta lactoglobulin IgG were practically unchanged. The total IgE values were unchanged in both groups. Over the study period, the PEFR in those children in the experimental group able to perform the test was significantly increased, but no such change was noted in the children in the control group who could do the test. These results suggest that even over the short time period of eight weeks, an egg- and milk-free diet can reduce atopic symptoms and improve lung function in asthmatic children.","title":"The effects of exclusion of dietary egg and milk in the management of asthmatic children: a pilot study."},{"docid":"MED-1716","text":"Obesity has reached epidemic proportions in the developed world. The progression from obesity to diabetes mellitus type 2, via metabolic syndrome, is recognised, and the significant associated increase in the risk of major human cancers acknowledged. We review the molecular basis of the involvement of morbidly high concentrations of endogenous or therapeutic insulin and of insulin-like growth factors in the progression from obesity to diabetes and finally to cancer. Epidemiological and biochemical studies establish the role of insulin and hyperinsulinaemia in cancer risk and progression. Insulin-like growth factors, IGF-1 and IGF-2, secreted by visceral or mammary adipose tissue have significant paracrine and endocrine effects. These effects can be exacerbated by increased steroid hormone production. Structural studies elucidate how each of the three ligands, insulin, IGF-1, and IGF-2, interacts differently with isoforms A and B of the insulin receptor and with type I IGF receptor and explain how these protagonists contribute to diabetes-associated cancer. The above should inform appropriate treatment of cancers that arise in obese individuals and in those with diabetes mellitus type 2. Novel drugs that target the insulin and insulin-like growth factor signal transduction pathways are in clinical trial and should be effective if appropriate biomarker-informed patient stratification is implemented.","title":"A Twenty-First Century Cancer Epidemic Caused by Obesity: The Involvement of Insulin, Diabetes, and Insulin-Like Growth Factors"},{"docid":"MED-3216","text":"Increasing dietary protein results in an increase in urinary calcium. Despite over 80 y of research, the source of the additional urinary calcium remains unclear. Because most calcium balance studies found little effect of dietary protein on intestinal calcium absorption, it was assumed that the skeleton was the source of the calcium. The hypothesis was that the high endogenous acid load generated by a protein-rich diet would increase bone resorption and skeletal fracture. However, there are no definitive nutrition intervention studies that show a detrimental effect of a high protein diet on the skeleton and the hypothesis remains unproven. Recent studies from our laboratory demonstrate that dietary protein affects intestinal calcium absorption. We conducted a series of short-term nutrition intervention trials in healthy adults where dietary protein was adjusted to either low, medium or high. The highest protein diet resulted in hypercalciuria with no change in serum parathyroid hormone. Surprisingly, within 4 d, the low protein diet induced secondary hyperparathyroidism that persisted for 2 wk. The secondary hyperparathyroidism induced by the low protein diet was attributed to a reduction in intestinal calcium absorption (as assessed by dual stable calcium isotopes). The long-term consequences of these low protein-induced changes in calcium metabolism are not known, but they could be detrimental to skeletal health. Several recent epidemiological studies demonstrate reduced bone density and increased rates of bone loss in individuals habitually consuming low protein diets. Therefore, studies are needed to determine whether low protein intakes directly affect rates of bone resorption, bone formation or both.","title":"Low protein intake: the impact on calcium and bone homeostasis in humans."},{"docid":"MED-3236","text":"A first objective of the present study was to estimate the acid-base balance of the food intake in vegetarians and non-vegetarians. A second objective was to evaluate if additional input of specific food items on the existing potential renal acid load (PRAL) list was necessary for the comparison of the two dietary patterns. Thirty vegetarians between the age of 18 and 30 years were matched for sex, age and BMI with 30 non-vegetarians. Based on the 3-days food diaries the acid-base status of the food intake was estimated using the PRAL method. Mean PRAL values as estimated with the standard table yielded an alkaline load of -5.4 +/- 14.4 mEq/d in the vegetarians compared to an acid load of 10.3 +/- 14.4 mEq/d in the nonvegetarians (p<0.001). Mean PRAL values as estimated with the extended table yielded an alkaline load of -10.9 +/-19.7 mEq/d in the vegetarians compared to an acid load of 13.8 +/- 17.1 mEq/d for the non-vegetarians (p<0.001). The findings of this study indicate that vegetarian food intake produces more alkaline outcomes compared to non-vegetarian diets. The use of the standard PRAL table was sufficient for discrimination between the two diets.","title":"Nutrient based estimation of acid-base balance in vegetarians and non-vegetarians."},{"docid":"MED-3315","text":"PURPOSE: To test the hypothesis that exposure to poultry oncogenic viruses that widely occurs occupationally in poultry workers and in the general population, may be associated with increased risks of deaths from liver and pancreatic cancers, and to identify new risk factors. METHODS: A pilot case-cohort study of both cancers within a combined cohort of 30,411 highly exposed poultry workers and 16,408 control subjects was conducted, and risk assessed by logistic regression odds ratios (OR) and proportional hazards risk ratios. RESULTS: New occupational findings were recorded respectively for pancreatic/liver cancers, for slaughtering of poultry (OR = 8.9, 95% confidence interval [CI]: 2.7-29.3)/OR = 9.1, 95% CI: 1.9-42.9); catching of live chickens (OR = 3.6, 95% CI: 1.2-10.9)/OR = 1.0, 95% CI: 0.1-8.5); killing other types of animals for food (OR = 4.8, 95% CI: 1.5-16.6)/OR = 2.0, 95% CI: 0.2-18.2), and ever worked on a pig raising farm (OR = 3.0, 95% CI: 1.0-8.2) for pancreatic cancer only. New non-occupational findings for liver cancer were for receiving immunization with yellow fever vaccine (OR = 8.7, 95% CI: 1.0-76.3); and vaccination with typhoid vaccine (OR = 6.3, 95% CI: 1.1-37.4). The study also confirmed previously reported risk factors for both diseases. CONCLUSIONS: This study provides preliminary evidence that exposure to poultry oncogenic viruses may possibly be associated with the occurrence of liver and pancreatic cancers. Case-control studies nested within occupational cohorts of highly exposed subjects of sufficient statistical power may provide an efficient and valid method of investigating/confirming these findings. Copyright © 2011 Elsevier Inc. All rights reserved.","title":"A pilot case-cohort study of liver and pancreatic cancers in poultry workers."},{"docid":"MED-3358","text":"BACKGROUND & AIMS: Taste sensitivity to fatty acids influences food ingestion and may regulate fat intake and body weight status. Fatty acids are detected via homologous receptors within the mouth and gastrointestinal (GI) tract, where attenuated sensitivity may be associated with greater fat intake and BMI. This study aimed to extend observations surrounding fatty acid taste, specifically the types of foods consumed and dietary behaviours that may be associated with fatty acid taste sensitivity. METHODS: 51 subjects (41 female; BMI, 21.4 ± 0.46 kg/m², age, 20 ± 0.52 yrs, 10 male; BMI, 23.6 ± 1.4 kg/m², age, 22 ± 1 yrs) were screened for oral sensitivity to oleic acid (3.8 mM) using triplicate sensory evaluations, and classified as hypersensitive; (3/3 correct identifications), or hyposensitive, (<3/3). Fat-taste perception (using sensory-matched custards made with 0, 2, 6, 10% oil), recent diet (4-day diet record) and food habits and behaviours (food habits and behaviours questionnaire) were also established. RESULTS: 75% (n = 38) of subjects were classified as hyposensitive to oleic acid and these subjects differed from those who were classified as hypersensitive. Hyposensitive subjects consumed significantly more energy, fat, saturated fat, fatty foods (butter, meat, dairy), had greater BMI and were less perceptive of small changes in the fat content of custard (all P < 0.05), compared to hypersensitive subjects. CONCLUSION: An inability to perceive low concentrations of fatty acids in foods was associated with greater consumption of fatty foods, specifically butter, meat, dairy, and increasing BMI. 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.","title":"Oral sensitivity to oleic acid is associated with fat intake and body mass index."},{"docid":"MED-3780","text":"Metabolomics studies hold promise for discovery of pathways linked to disease processes. Cardiovascular disease (CVD) represents the leading cause of death and morbidity worldwide. A metabolomics approach was used to generate unbiased small molecule metabolic profiles in plasma that predict risk for CVD. Three metabolites of the dietary lipid phosphatidylcholine, namely choline, trimethylamine N-oxide (TMAO), and betaine, were identified and then shown to predict risk for CVD in an independent large clinical cohort. Dietary supplementation of mice with choline, TMAO or betaine promoted up-regulation of multiple macrophage scavenger receptors linked to atherosclerosis, and supplementation with choline or TMAO promoted atherosclerosis. Studies using germ-free mice confirmed a critical role for dietary choline and gut flora in TMAO production, augmented macrophage cholesterol accumulation and foam cell formation. Suppression of intestinal microflora in atherosclerosis-prone mice inhibited dietary choline-enhanced atherosclerosis. Genetic variations controlling expression of flavin monooxygenases (FMOs), an enzymatic source of TMAO, segregated with atherosclerosis in hyperlipidemic mice. Discovery of a relationship between gut flora-dependent metabolism of dietary phosphatidylcholine and CVD pathogenesis provides opportunities for development of both novel diagnostic tests and therapeutic approaches for atherosclerotic heart disease.","title":"Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease"},{"docid":"MED-3227","text":"Although high-protein diets induce hypercalciuria in humans, the source of the additional urinary calcium remains unclear. One hypothesis is that the high endogenous acid load of a high-protein diet is partially buffered by bone, leading to increased skeletal resorption and hypercalciuria. We used dual stable calcium isotopes to quantify the effect of a high-protein diet on calcium kinetics in women. The study consisted of 2 wk of a lead-in, well-balanced diet followed by 10 d of an experimental diet containing either moderate (1.0 g/kg) or high (2.1 g/kg) protein. Thirteen healthy women received both levels of protein in random order. Intestinal calcium absorption increased during the high-protein diet in comparison with the moderate (26.2 +/- 1.9% vs. 18.5 +/- 1.6%, P < 0.0001, mean +/- sem) as did urinary calcium (5.23 +/- 0.37 vs. 3.57 +/- 0.35 mmol/d, P < 0.0001, mean +/- sem). The high-protein diet caused a significant reduction in the fraction of urinary calcium of bone origin and a nonsignificant trend toward a reduction in the rate of bone turnover. There were no protein-induced effects on net bone balance. These data directly demonstrate that, at least in the short term, high-protein diets are not detrimental to bone.","title":"The impact of dietary protein on calcium absorption and kinetic measures of bone turnover in women."},{"docid":"MED-3352","text":"The popularity of low- and reduced-fat foods has increased as consumers seek to decrease their energy consumption. Fat replacers may be used in fat-reduced products to maintain their sensory properties. However, these ingredients have been largely formulated to replicate nongustatory properties of fats to foods and have only achieved moderate success. There is increasing evidence that fats also activate the taste system and uniquely evoke responses that may influence product acceptance. Work supporting a taste component of fat has prompted questions about whether fat constitutes an additional \"primary\" or \"basic\" taste quality. This review briefly summarizes this evidence, focusing on human studies, when possible. Effective stimuli, possible receptors, and physiological changes due to oral fat exposure are discussed. Some studies suggest that there are fatty acid tasters and nontasters and if verified could have implications for targeted product development. © 2011 Institute of Food Technologists®","title":"Are free fatty acids effective taste stimuli in humans? Presented at the symposium \"The Taste for Fat: New Discoveries on the Role of Fat in Sensor..."},{"docid":"MED-3138","text":"Background Many consumers avoid eating beans because they believe legume consumption will cause excessive intestinal gas or flatulence. An increasing body of research and the 2010 Dietary Guidelines for Americans supports the benefits of a plant-based diet, and legumes specifically, in the reduction of chronic disease risks. The purpose of the current research was to investigate the perception of increased flatulence and gastrointestinal discomfort among participants who consumed a ½ cup of beans daily for 8 or 12 weeks. Methods Participants in three studies to test the effects of beans on heart disease biomarkers completed the same weekly questionnaire to assess gastrointestinal discomfort issues such as increased flatulence, stool changes, and bloating. Studies 1 and 2 were randomized crossover trials. Participants consumed ½ cup of pinto beans, black-eyed peas, and canned carrots as control (n = 17) in Study 1 for three randomized 8-week phases. For Study 2, participants ate ½ cup baked beans or canned carrots as control (n = 29) for two randomized 8-week phases. Study 3 was a parallel arm trial with 40 subjects receiving ½ cup pinto beans and 40 consuming a control soup for 12 weeks. Changes in the frequency of perceived flatulence, stool characteristics, and bloating were the primary outcome measures. Chi-square distributions were examined for the presence or absence of symptoms and demographic characteristics to determine differences by gender, age, body mass index (BMI), and bean type. Results Less than 50% reported increased flatulence from eating pinto or baked beans during the first week of each trial, but only 19% had a flatulence increase with black-eyed peas. A small percentage (3-11%) reported increased flatulence across the three studies even on control diets without flatulence-producing components. Conclusions People's concerns about excessive flatulence from eating beans may be exaggerated. Public health nutritionists should address the potential for gastrointestinal discomfort when increasing fiber intake from beans with clients. It is important to recognize there is individual variation in response to different bean types.","title":"Perceptions of flatulence from bean consumption among adults in 3 feeding studies"},{"docid":"MED-3140","text":"To identify protective dietary predictors amongst long-lived elderly people (N= 785), the \"Food Habits in Later Life \"(FHILL) study was undertaken among five cohorts in Japan, Sweden, Greece and Australia. Between 1988 and 1991, baseline data on food intakes were collected. There were 785 participants aged 70 and over that were followed up to seven years. Based on an alternative Cox Proportional Hazard model adjusted to age at enrollment (in 5-year intervals), gender and smoking, the legume food group showed 7-8% reduction in mortality hazard ratio for every 20g increase in daily intake with or without controlling for ethnicity (RR 0.92; 95% CI 0.85-0.99 and RR 0.93; 95% CI 0.87-0.99, respectively). Other food groups were not found to be consistently significant in predicting survival amongst the FHILL cohorts.","title":"Legumes: the most important dietary predictor of survival in older people of different ethnicities."},{"docid":"MED-2200","text":"Cancer of the gallbladder is rare but fatal, and has an unusual geographic and demographic distribution. Gallstones and obesity have been suggested as possible risk factors. As diet is known to influence both these factors, we carried out the present study to evaluate the possible role of diet in gallbladder carcinogenesis. A case-control study involving 64 newly diagnosed cases of gallbladder cancer and 101 cases of gallstones was carried out. The dietary evaluation was carried out by the dietary recall method based on a preset questionnaire developed specifically for the present study, keeping in mind the common dietary habits prevailing in this part of the world. Odds ratios (OR) and 95% confidence interval (CI) were calculated for various dietary items. A significant reduction in odds ratio was seen with the consumption of radish (OR 0.4; 95% CI 0.17-0.94), green chilli (OR 0.45; 95% CI 0.21-0.94) and sweet potato (OR 0.33; 95% CI 0.13-0.83) among vegetables, and mango (OR 0.4; 95% CI 0.16-0.99), orange (OR; 0.45; 95% CI 0.22-0.93), melon (OR 0.3; 95% CI 0.14-0.64) and papaya (OR 0.44; 95% 0.2-0.64) among fruits. A reduction in odds was also seen with the consumption of cruciferous vegetables, beans, onion and turnip, however the difference was not statistically significant. On the other hand, an increase in the odds was observed with consumption of capsicum (OR 2.2), beef (OR 2.58), tea (OR 1.98), red chilli (OR 1.29) and mutton (OR 1.2), however the difference was statistically not significant. In conclusion, the results of the present study show a protective effect of vegetables and fruits on gallbladder carcinogenesis, but red meat (beef and mutton) was found to be associated with increased risk of gallbladder cancer.","title":"Diet and gallbladder cancer: a case-control study."},{"docid":"MED-2367","text":"Naturally developing xenospecific Abs are well-documented barriers to xenograft transplantation in humans, but whether analogous xenoreactive T cell immunity develops is not known. We used an enzyme-linked immunospot assay to determine the frequency and cytokine profiles of xenoreactive PBLs from a panel of human volunteers. Because naive T cells produce only IL-2 in short term culture, IFN-gamma production by this approach is a measure of a memory immune response. Stimulation of human PBLs or purified T lymphocytes with stimulator cells from inbred swine revealed a high frequency of IFN-gamma producers with 5-fold fewer IL-2 producers. In contrast, lymphocytes obtained from neonatal umbilical cord blood contained swine-specific IL-2 producers but few IFN-gamma producers, which is what one would expect to find with a naive phenotype. Moreover, PBLs from adults with a history of abstention from pork consumption responded to swine cells with a significantly lower frequency of IFN-gamma producers than PBLs from adults with unrestricted diets did, suggesting that pork consumption may result in priming of swine-specific T cell immunity. Our findings provide the first evidence for naturally occurring xenospecific T cell immunity in humans. The detected strength of this memory response suggests that it will present a formidable barrier to transplantation of swine organs.","title":"Naturally developing memory T cell xenoreactivity to swine antigens in human peripheral blood lymphocytes."},{"docid":"MED-4299","text":"The evolution of the human diet over the past 10,000 years from a Paleolithic diet to our current modern pattern of intake has resulted in profound changes in feeding behavior. Shifts have occurred from diets high in fruits, vegetables, lean meats, and seafood to processed foods high in sodium and hydrogenated fats and low in fiber. These dietary changes have adversely affected dietary parameters known to be related to health, resulting in an increase in obesity and chronic disease, including cardiovascular disease (CVD), diabetes, and cancer. Some intervention trials using Paleolithic dietary patterns have shown promising results with favorable changes in CVD and diabetes risk factors. However, such benefits may be offset by disadvantages of the Paleolithic diet, which is low in vitamin D and calcium and high in fish potentially containing environmental toxins. More advantageous would be promotion of foods and food ingredients from our ancestral era that have been shown to possess health benefits in the form of functional foods. Many studies have investigated the health benefits of various functional food ingredients, including omega-3 fatty acids, polyphenols, fiber, and plant sterols. These bioactive compounds may help to prevent and reduce incidence of chronic diseases, which in turn could lead to health cost savings ranging from $2 to $3 billion per year as estimated by case studies using omega-3 and plant sterols as examples. Thus, public health benefits should result from promotion of the positive components of Paleolithic diets as functional foods.","title":"Evolution of the human diet: linking our ancestral diet to modern functional foods as a means of chronic disease prevention."},{"docid":"MED-2451","text":"BACKGROUND—A prospective cohort study of 2512 Welshmen aged 45-59 living in Caerphilly in 1979-1983 was used to investigate associations between diet and lung function. METHODS—At baseline (phase I) and at five year follow up (phase II), forced expiratory volume in one second (FEV1) was measured using a McDermott spirometer and dietary data were obtained using a semi-quantitative food frequency questionnaire. RESULTS—Good lung function, indicated by high maximum FEV1 given age and height, was associated with high intakes of vitamin C, vitamin E, β-carotene, citrus fruit, apples, and the frequent consumption of fruit juices/squashes. Lung function was inversely associated with magnesium intake but there was no evidence of an association with fatty fish. Following adjustment for confounders including body mass index, smoking history, social class, exercise, and total energy intake, only the associations with vitamin E and apples persisted, with lung function estimated to be 39 ml (95% confidence interval (CI) 9 to 69) higher for vitamin E intakes one standard deviation (SD) apart and 138 ml higher (95% CI 58to 218) for those eating five or more apples per week compared with non-consumers. Decline in lung function between phases was not significantly associated with the changing intakes of apples or vitamin E. An association between high average apple consumption and slow decline in lung function lost significance after adjustment for confounders. CONCLUSIONS—A strong positive association is seen between lung function and the number of apples eaten per week cross sectionally, consistent with a protective effect of hard fruit rather than soft/citrus fruit. The recent suggestion that such effects are reversible was not supported by our longitudinal analysis.","title":"Diet, lung function, and lung function decline in a cohort of 2512 middle aged men"},{"docid":"MED-3320","text":"OBJECTIVES: Reticuloendotheliosis viruses (REV) are a group of retroviruses like avian leukosis/sarcoma viruses (ALSV) that naturally infect and cause cancers in chickens. We recently found that ALSV antibody levels were associated with job tasks in the poultry industry. The objectives of this study are to examine whether a similar association can be found with REV antibody levels and to examine the correlation between REV and ALSV antibody levels. METHODS: Relative risk was estimated comparing REV antibody levels of 45 poultry workers with those of 44 controls. The expected mean antibody level was predicted for the association with employment by a generalized linear model. Correlation coefficient was measured between ALSV and REV antibody levels. RESULTS: REV antibody levels were significantly higher in poultry workers than in control subjects and were associated with gender and employment conditions, especially employment duration. The relative risk was significantly higher for some job categories. A significant correlation was observed between REV and ALSV antibody levels, which was strong among poultry workers, but weak among the control subjects. CONCLUSION: Antibody levels can be validly used to identify certain job tasks associated with high risk of exposure to REV in the workplace, and the practical implication is recommendations for protection at these job tasks. Importantly, in situations where there is exposure to multiple pathogens in the workplace, the analysis of antibody levels of one pathogen may sufficiently represent exposure to the other correlated pathogens. This suggested exposure assessment may hold true for pathogens with a similar route of transmission.","title":"Industrial hygiene assessment of reticuloendotheliosis viruses exposure in the poultry industry."},{"docid":"MED-4515","text":"BACKGROUND: Low-carbohydrate, high-animal protein diets, which are advocated for weight loss, may not promote the desired reduction in low-density lipoprotein cholesterol (LDL-C) concentration. The effect of exchanging the animal proteins and fats for those of vegetable origin has not been tested. Our objective was to determine the effect on weight loss and LDL-C concentration of a low-carbohydrate diet high in vegetable proteins from gluten, soy, nuts, fruits, vegetables, cereals, and vegetable oils compared with a high-carbohydrate diet based on low-fat dairy and whole grain products. METHODS: A total of 47 overweight hyperlipidemic men and women consumed either (1) a low-carbohydrate (26% of total calories), high-vegetable protein (31% from gluten, soy, nuts, fruit, vegetables, and cereals), and vegetable oil (43%) plant-based diet or (2) a high-carbohydrate lacto-ovo vegetarian diet (58% carbohydrate, 16% protein, and 25% fat) for 4 weeks each in a parallel study design. The study food was provided at 60% of calorie requirements. RESULTS: Of the 47 subjects, 44 (94%) (test, n = 22 [92%]; control, n = 22 [96%]) completed the study. Weight loss was similar for both diets (approximately 4.0 kg). However, reductions in LDL-C concentration and total cholesterol-HDL-C and apolipoprotein B-apolipoprotein AI ratios were greater for the low-carbohydrate compared with the high-carbohydrate diet (-8.1% [P = .002], -8.7% [P = .004], and -9.6% [P = .001], respectively). Reductions in systolic and diastolic blood pressure were also seen (-1.9% [P = .052] and -2.4% [P = .02], respectively). CONCLUSION: A low-carbohydrate plant-based diet has lipid-lowering advantages over a high-carbohydrate, low-fat weight-loss diet in improving heart disease risk factors not seen with conventional low-fat diets with animal products.","title":"The effect of a plant-based low-carbohydrate (\"Eco-Atkins\") diet on body weight and blood lipid concentrations in hyperlipidemic subjects."},{"docid":"MED-3456","text":"Pharmacological antioxidant vitamins have previously been investigated for a prophylactic effect against exercise-induced oxidative stress. However, large doses are often required and may lead to a state of pro-oxidation and oxidative damage. Watercress contains an array of nutritional compounds such as β-carotene and α-tocopherol which may increase protection against exercise-induced oxidative stress. The present randomised controlled investigation was designed to test the hypothesis that acute (consumption 2 h before exercise) and chronic (8 weeks consumption) watercress supplementation can attenuate exercise-induced oxidative stress. A total of ten apparently healthy male subjects (age 23 (SD 4) years, stature 179 (SD 10) cm and body mass 74 (SD 15) kg) were recruited to complete the 8-week chronic watercress intervention period (and then 8 weeks of control, with no ingestion) of the experiment before crossing over in order to compete the single-dose acute phase (with control, no ingestion). Blood samples were taken at baseline (pre-supplementation), at rest (pre-exercise) and following exercise. Each subject completed an incremental exercise test to volitional exhaustion following chronic and acute watercress supplementation or control. The main findings show an exercise-induced increase in DNA damage and lipid peroxidation over both acute and chronic control supplementation phases (P< 0.05 v. supplementation), while acute and chronic watercress attenuated DNA damage and lipid peroxidation and decreased H₂O₂ accumulation following exhaustive exercise (P< 0.05 v. control). A marked increase in the main lipid-soluble antioxidants (α-tocopherol, γ-tocopherol and xanthophyll) was observed following watercress supplementation (P< 0.05 v. control) in both experimental phases. These findings suggest that short- and long-term watercress ingestion has potential antioxidant effects against exercise-induced DNA damage and lipid peroxidation.","title":"Acute and chronic watercress supplementation attenuates exercise-induced peripheral mononuclear cell DNA damage and lipid peroxidation."},{"docid":"MED-2471","text":"The International Study of Asthma and Allergies in Childhood (ISAAC) Phase One showed large worldwide variations in the prevalence of symptoms of asthma, rhinoconjunctivitis and eczema, up to 10 to 20 fold between countries. Ecological analyses were undertaken with ISAAC Phase One data to explore factors that may have contributed to these variations, and are summarised and reviewed here. In ISAAC Phase One the prevalence of symptoms in the past 12 months of asthma, rhinoconjunctivitis and eczema were estimated from studies in 463,801 children aged 13 - 14 years in 155 centres in 56 countries, and in 257,800 children aged 6-7 years in 91 centres in 38 countries. Ecological analyses were undertaken between symptom prevalence and the following: Gross National Product per capita (GNP), food intake, immunisation rates, tuberculosis notifications, climatic factors, tobacco consumption, pollen, antibiotic sales, paracetamol sales, and outdoor air pollution. Symptom prevalence of all three conditions was positively associated with GNP, trans fatty acids, paracetamol, and women smoking, and inversely associated with food of plant origin, pollen, immunisations, tuberculosis notifications, air pollution, and men smoking. The magnitude of these associations was small, but consistent in direction between conditions. There were mixed associations of climate and antibiotic sales with symptom prevalence. The potential causality of these associations warrant further investigation. Factors which prevent the development of these conditions, or where there is an absence of a positive correlation at a population level may be as important from the policy viewpoint as a focus on the positive risk factors. Interventions based on small associations may have the potential for a large public health benefit.","title":"Which population level environmental factors are associated with asthma, rhinoconjunctivitis and eczema? Review of the ecological analyses of ISAAC Phase One"},{"docid":"MED-2484","text":"Paediatric asthma is a major clinical concern worldwide and represents a huge burden on family and society. It accounts for a large number of lost school days and may deprive the child of both academic achievement and social interaction. Childhood asthma also places strain on healthcare resources as a result of doctor and hospital visits and the cost of treatment. The prevalence of asthma varies worldwide, possibly because of different exposure to respiratory infection, indoor and outdoor pollution, and diet. Certain risk factors appear to predispose children to developing asthma and atopic disease, including incidence and severity of wheezing, atopy, maternal smoking, and number of fever episodes. This paper discusses the burden, prevalence, and risk factors associated with paediatric asthma.","title":"The burden of childhood asthma"},{"docid":"MED-3233","text":"Our objective in this study was to determine the effects of a high-protein and high-potential renal acid load (PRAL) diet on calcium (Ca) absorption and retention and markers of bone metabolism. In a randomized crossover design, 16 postmenopausal women consumed 2 diets: 1 with low protein and low PRAL (LPLP; total protein: 61 g/d; PRAL: -48 mEq/d) and 1 with high protein and high PRAL (HPHP; total protein: 118 g/d; PRAL: 33 mEq/d) for 7 wk each separated by a 1-wk break. Ca absorption was measured by whole body scintillation counting of radio-labeled (47)Ca. Compared with the LPLP diet, the HPHP diet increased participants' serum IGF-I concentrations (P < 0.0001), decreased serum intact PTH concentrations (P < 0.001), and increased fractional (47)Ca absorption (mean ± pooled SD: 22.3 vs. 26.5 ± 5.4%; P < 0.05) and urinary Ca excretion (156 vs. 203 ± 63 mg/d; P = 0.005). The net difference between the amount of Ca absorbed and excreted in urine did not differ between 2 diet periods (55 vs. 28 ± 51 mg/d). The dietary treatments did not affect other markers of bone metabolism. In summary, a diet high in protein and PRAL increases the fractional absorption of dietary Ca, which partially compensates for increased urinary Ca, in postmenopausal women. The increased IGF-I and decreased PTH concentrations in serum, with no change in biomarkers of bone resorption or formation, indicate a high-protein diet has no adverse effects on bone health.","title":"A diet high in meat protein and potential renal acid load increases fractional calcium absorption and urinary calcium excretion without affecting m..."},{"docid":"MED-3373","text":"Objectives. We considered the relationship between an urban adult population's fruit and vegetable consumption and several selected social and psychological processes, beneficial aesthetic experiences, and garden participation. Methods. We conducted a population-based survey representing 436 residents across 58 block groups in Denver, Colorado, from 2006 to 2007. We used multilevel statistical models to evaluate the survey data. Results. Neighborhood aesthetics, social involvement, and community garden participation were significantly associated with fruit and vegetable intake. Community gardeners consumed fruits and vegetables 5.7 times per day, compared with home gardeners (4.6 times per day) and nongardeners (3.9 times per day). Moreover, 56% of community gardeners met national recommendations to consume fruits and vegetables at least 5 times per day, compared with 37% of home gardeners and 25% of nongardeners. Conclusions. Our study results shed light on neighborhood processes that affect food-related behaviors and provides insights about the potential of community gardens to affect these behaviors. The qualities intrinsic to community gardens make them a unique intervention that can narrow the divide between people and the places where food is grown and increase local opportunities to eat better.","title":"The Influence of Social Involvement, Neighborhood Aesthetics, and Community Garden Participation on Fruit and Vegetable Consumption"},{"docid":"MED-3453","text":"There has been no investigation to determine if the widely used over-the-counter, water-soluble antioxidants vitamin C and N-acetyl-cysteine (NAC) could act as pro-oxidants in humans during inflammatory conditions. We induced an acute-phase inflammatory response by an eccentric arm muscle injury. The inflammation was characterized by edema, swelling, pain, and increases in plasma inflammatory indicators, myeloperoxidase and interleukin-6. Immediately following the injury, subjects consumed a placebo or vitamin C (12.5 mg/kg body weight) and NAC (10 mg/kg body weight) for 7 d. The resulting muscle injury caused increased levels of serum bleomycin-detectable iron and the amount of iron was higher in the vitamin C and NAC group. The concentrations of lactate dehydrogenase (LDH), creatine kinase (CK), and myoglobin were significantly elevated 2, 3, and 4 d postinjury and returned to baseline levels by day 7. In addition, LDH and CK activities were elevated to a greater extent in the vitamin C and NAC group. Levels of markers for oxidative stress (lipid hydroperoxides and 8-iso prostaglandin F2alpha; 8-Iso-PGF2alpha) and antioxidant enzyme activities were also elevated post-injury. The subjects receiving vitamin C and NAC had higher levels of lipid hydroperoxides and 8-Iso-PGF2alpha 2 d after the exercise. This acute human inflammatory model strongly suggests that vitamin C and NAC supplementation immediately post-injury, transiently increases tissue damage and oxidative stress.","title":"Supplementation with vitamin C and N-acetyl-cysteine increases oxidative stress in humans after an acute muscle injury induced by eccentric exercise."},{"docid":"MED-3789","text":"Background: Meat, milk, and eggs have been inconsistently associated with the risk of advanced prostate cancer. These foods are sources of choline—a nutrient that may affect prostate cancer progression through cell membrane function and one-carbon metabolism. No study has examined dietary choline and the risk of lethal prostate cancer. Objective: Our objective was to examine whether dietary choline, choline-containing compounds, and betaine (a choline metabolite) increase the risk of lethal prostate cancer. Design: We prospectively examined the intake of these nutrients and the risk of lethal prostate cancer among 47,896 men in the Health Professionals Follow-Up Study. In a case-only survival analysis, we examined the postdiagnostic intake of these nutrients and the risk of lethal prostate cancer among 4282 men with an initial diagnosis of nonmetastatic disease during follow-up. Diet was assessed with a validated questionnaire 6 times during 22 y of follow-up. Results: In the incidence analysis, we observed 695 lethal prostate cancers during 879,627 person-years. Men in the highest quintile of choline intake had a 70% increased risk of lethal prostate cancer (HR: 1.70; 95% CI: 1.18, 2.45; P-trend = 0.005). In the case-only survival analysis, we observed 271 lethal cases during 33,679 person-years. Postdiagnostic choline intake was not statistically significantly associated with the risk of lethal prostate cancer (HR for quintile 5 compared with quintile 1: 1.69; 95% CI: 0.93, 3.09; P-trend = 0.20). Conclusion: Of the 47,896 men in our study population, choline intake was associated with an increased risk of lethal prostate cancer.","title":"Choline intake and risk of lethal prostate cancer: incidence and survival"},{"docid":"MED-2205","text":"AIM: To investigate the effects of proteins purified from sweet potato storage roots on human colorectal cancer cell lines. METHODS: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Hoechst 33258 nuclear staining and Boyden transwell chamber methods were used to determine whether purified sweet potato protein (SPP) from fresh sweet potato roots affected proliferation, migration and invasion, respectively, of human colorectal cancer SW480 cells in vitro. The inhibitory effects of SPP on growth of human colorectal cancer HCT-8 cells intraperitoneally xenografted in nude mice and spontaneous lung metastasis of murine Lewis lung carcinoma 3LL cells subcutaneously transplanted in C57 BL/6 mice were also investigated in vivo. RESULTS: SPP inhibited the proliferation of SW480 cells in a dose-dependent manner, with an IC50 value of 38.732 μmol/L (r2 = 0.980, P = 0.003) in the MTT assay. Hoechst 33258 nuclear staining further revealed inhibition of cell viability and induction of apoptosis by SPP. The transwell assay disclosed significant reduction in migrated cells/field by 8 μmol/L SPP (8.4 ± 2.6 vs 23.3 ± 5.4, P = 0.031) and invaded cells/field through the ECMatrix by 0.8 μmol/L SPP, compared with the control (25.2 ± 5.2 vs 34.8 ± 6.1, P = 0.038). Both intraperitoneal (ip) and intragastric (ig) administration of SPP led to significant suppression of growth of intraperitoneally inoculated HCT-8 cells in nude mice to 58.0% ± 5.9% (P = 0.037) and 43.5% ± 7.1% (P = 0.004) of the controls, respectively, after 9 d treatment. Bloody ascites additionally disappeared after ip injection of trypsin inhibitor. Notably, ig and ip administration of SPP induced a significant decrease in spontaneous pulmonary metastatic nodule formation in C57 BL/6 mice (21.0 ± 12.3 and 27.3 ± 12.7 nodules/lung vs 42.5 ± 4.5 nodules/lung in controls, respectively, P < 0.05) after 25 d treatment. Moreover, the average weight of primary tumor nodules in the hind leg of mice decreased from 8.2 ± 1.3 g/mice in the control to 6.1 ± 1.4 g/mice in the ip group (P = 0.035). CONCLUSION: SPP exerts significant antiproliferative and antimetastatic effects on human colorectal cancer cell lines, both in vitro and in vivo.","title":"Anticancer effects of sweet potato protein on human colorectal cancer cells"},{"docid":"MED-3294","text":"In the past two decades or so, a number of viruses have emerged in the global swine population. Some, such as porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2), cause economically important diseases in pigs, whereas others such as porcine torque teno virus (TTV), now known as Torque teno sus virus (TTSuV), porcine bocavirus (PBoV) and related novel parvoviruses, porcine kobuvirus, porcine toroviruses (PToV) and porcine lymphotropic herpesviruses (PLHV), are mostly subclinical in swine herds. Although some emerging swine viruses such as swine hepatitis E virus (swine HEV), porcine endogenous retrovirus (PERV) and porcine sapovirus (porcine SaV) may have a limited clinical implication in swine health, they do pose a potential public health concern in humans due to zoonotic (swine HEV) or potential zoonotic (porcine SaV) and xenozoonotic (PERV, PLHV) risks. Other emerging viruses such as Nipah virus, Bungowannah virus and Menangle virus not only cause diseases in pigs but some also pose important zoonotic threat to humans. This article focuses on emerging and re-emerging swine viruses that have a limited or uncertain clinical and economic impact on pig health. The transmission, epidemiology and pathogenic potential of these viruses are discussed. In addition, the two economically important emerging viruses, PRRSV and PCV2, are also briefly discussed to identify important knowledge gaps. © 2012 Blackwell Verlag GmbH.","title":"Emerging and re-emerging swine viruses."},{"docid":"MED-1257","text":"Meat protein is associated with an increase in risk of heart disease. Recent data have shown that meat protein appeared to be associated with weight gain over 6.5 years, with 1 kg of weight increase per 125 g of meat per day. In the Nurses' Health Study, diets low in red meat, containing nuts, low-fat dairy, poultry, or fish, were associated with a 13% to 30% lower risk of CHD compared with diets high in meat. Low-carbohydrate diets high in animal protein were associated with a 23% higher total mortality rate whereas low-carbohydrate diets high in vegetable protein were associated with a 20% lower total mortality rate. Recent soy interventions have been assessed by the American Heart Association and found to be associated with only small reductions in LDL cholesterol. Although dairy intake has been associated with a lower weight and lower insulin resistance and metabolic syndrome, the only long-term (6 months) dairy intervention performed so far has shown no effects on these parameters.","title":"Protein and coronary heart disease: the role of different protein sources."},{"docid":"MED-2364","text":"We have recently demonstrated that both antibodies to Gal alpha(1,3)Gal, and the Gal alpha(1,3)Gal binding lectin (IB4), bind a synthetic peptide (DAHWESWL), there being a similar recognition of carbohydrate and peptide structures. We now report that the anti-Gal alpha(1,3)Gal antibodies and IB4 lectin also react with peptides encoded by mucin genes (MUC 1, 3, 4)-sequences known to be rich in serine, threonine and proline. This activity was demonstrated (1) by the ability of mucin derived peptides to block the reaction of anti-Gal alpha(1,3)Gal antibodies and IB4 lectin with a Gal alpha(1,3)Gal+ pig endothelial cell line; the reactions were specific and did not occur with a random peptide containing the same sequences or with other mucin peptides; (2) by the fact that anti-mucin1 antibodies could react with the Gal alpha(1,3)Gal expressed after transfection of COS cells (Gal alpha(1,3)Gal-,Muc1-) with cDNA encoding the pig alpha, 3galactosyltransferase; and (3) that the IB4 lectin and anti-Gal alpha(1,3)Gal antibodies could react with mucin 1 found on the surface of human breast cancer cells. Thus natural occurring anti-Gal alpha(1,3)Gal antibodies found in all human serum can react with self (Muc1) peptides expressed in large amounts on the surface of tumour cells but not on normal cells. The findings are of interest and serve to explain the previously reported findings that human cells can, at times, express Gal alpha(1,3)Gal; such expression is an artefact, the reaction is due to the phenomenon described herein, i.e. that anti-Gal alpha(1,3)Gal antibodies react with mucin peptides.","title":"Natural human anti-Gal alpha(1,3)Gal antibodies react with human mucin peptides."},{"docid":"MED-3353","text":"Skin blood perfusion and oxygenation depends upon cardiovascular, hormonal and circulatory health in humans and provides socio-sexual signals of underlying physiology, dominance and reproductive status in some primates. We allowed participants to manipulate colour calibrated facial photographs along empirically-measured oxygenated and deoxygenated blood colour axes both separately and simultaneously, to optimise healthy appearance. Participants increased skin blood colour, particularly oxygenated, above basal levels to optimise healthy appearance. We show, therefore, that skin blood perfusion and oxygenation influence perceived health in a way that may be important to mate choice.","title":"Skin Blood Perfusion and Oxygenation Colour Affect Perceived Human Health"},{"docid":"MED-3371","text":"Background: The overconsumption of energy-dense foods leads to excessive energy intakes. The substitution of low-energy-dense vegetables for foods higher in energy density can help decrease energy intakes but may be difficult to implement if individuals dislike the taste of vegetables. Objective: We investigated whether incorporating puréed vegetables to decrease the energy density of entrées at multiple meals reduced daily energy intakes and increased daily vegetable intakes. Design: In this crossover study, 20 men and 21 women ate ad libitum breakfast, lunch, and dinner in the laboratory once a week for 3 wk. Across conditions, entrées at meals varied in energy density from standard versions (100% condition) to reduced versions (85% and 75% conditions) by the covert incorporation of 3 or 4.5 times the amount of puréed vegetables. Entrées were accompanied by unmanipulated side dishes. Participants rated their hunger and fullness before and after meals. Results: Subjects consumed a consistent weight of foods across conditions of energy density; thus, the daily energy intake significantly decreased by 202 ± 60 kcal in the 85% condition (P < 0.001) and by 357 ± 47 kcal in the 75% condition (P < 0.0001). Daily vegetable consumption significantly increased from 270 ± 17 g of vegetables in the 100% condition to 487 ± 25 g of vegetables in the 75% condition (P < 0.0001). Despite the decreased energy intake, ratings of hunger and fullness did not significantly differ across conditions. Entrées were rated as similar in palatability across conditions. Conclusions: Large amounts of puréed vegetables can be incorporated into various foods to decrease the energy density. This strategy can lead to substantial reductions in energy intakes and increases in vegetable intakes. This trial was registered at clinicaltrials.gov as NCT01165086.","title":"Hidden vegetables: an effective strategy to reduce energy intake and increase vegetable intake in adults"},{"docid":"MED-3243","text":"OBJECTIVES: Considerable evidence has shown that diet can affect both the incidence and the progression of prostate cancer. The objective of this study was to determine whether men in this situation could make a change to a diet emphasizing plant-based foods and fish and to examine the effect on quality of life (QOL) and prostate-specific antigen (PSA) velocity. METHODS: A total of 36 men and their partners were randomly assigned to attend a series of 11 dietary and cooking classes that also integrated mindfulness practice as a support in making the change or a wait-list control group. Assessments were made of dietary intake, QOL, and PSA at baseline, after intervention (11 weeks), and 3 months after intervention. RESULTS: The intervention group showed significant reductions in the consumption of saturated fat and increased consumption of vegetable proteins with accompanying reductions in animal proteins, including dairy products. They also showed increased QOL. Although no significant change was found in the rate of PSA increase between the two groups, the mean PSA doubling time for the intervention group was substantially longer at the 3-month follow-up visit than that of the controls. CONCLUSIONS: Men with a increasing PSA level after primary treatment were able to make a change to a prostate-healthy diet, accompanied by increases in QOL. No significant difference was found in the log PSA slope between the two groups; however, the PSA doubling time increased substantially in the intervention group compared with that in the controls. Future trials should examine the effect of the prostate-healthy diet with a larger sample of men for a longer period.","title":"A dietary intervention for recurrent prostate cancer after definitive primary treatment: results of a randomized pilot trial."},{"docid":"MED-3317","text":"Twenty-four patients, all of whom were exposed to aerosolized porcine brain tissue through work-place environment (abattoir), developed a syndrome of immune-mediated polyradiculoneuropathy; three also had central nervous system manifestations (transverse myelitis, meningoencephalitis, and aseptic meningitis). Patients had characteristic electrophysiological findings of very distal and proximal conduction slowing (prolonged distal and F-wave latencies, regions where the blood-nerve barrier is the most permeable) and all patients' serum contained a novel IgG immunofluorescence pattern. Nerve pathology, when available, showed mild changes of segmental demyelination, axonal degeneration, and inflammatory changes. Patients had meaningful improvement of symptoms and electrophysiologic findings with immune therapy and with removal of exposure to aerosolized brain tissue. We postulate that this outbreak is an auto-immune polyradiculoneuropathy triggered by occupational exposure to multiple aerosolized porcine neural tissue antigens that result in neural damage where the blood-nerve barrier is the least robust. © 2011 Peripheral Nerve Society.","title":"Auto-immune polyradiculoneuropathy and a novel IgG biomarker in workers exposed to aerosolized porcine brain."},{"docid":"MED-2292","text":"In industrialized nations, diverticular disease affects up to 70% of individuals by 60 years of age, with symptoms that can range from mild gastrointestinal disturbance to incapacitating pain. Diverticular disease appears to be related to increasing affluence and changed diet: Current theory holds that diverticular disease's origin is low-fiber diet. This explains why its incidence is highest and accelerating in the more prosperous countries where intake of fiber has decreased and intake of milled grains and refined sugars has increased over time. Not all patients develop symptoms, but if they do, the most frequent complaints associated with diverticulosis are cramping in the left-lower quadrant, bloating, constipation, and soiling. If diverticula perforate the gut's wall into the pericolic tissue, small and large abscesses, accompanied by bleeding, can form. Fistulization, when it occurs, most often penetrates to the bladder. Treatment addresses symptoms and may require hospitalization. During symptomatic periods, patients do best on low-fiber, bland diets. Once the acute episode or highly symptomatic period resolves or chronic disease is managed, patients should gradually increase dietary fiber to 20 to 30 grams daily or take dietary fiber in the form of bulk stimulants like psyllium.","title":"Diverticular disease: eat your fiber!"},{"docid":"MED-2354","text":"A new natural anti-alpha-galactosyl IgG antibody (anti-Gal) was found to be present in high titer in the serum of every normal individual studied. The antibody was isolated by affinity chromatography on a melibiose-Sepharose column. The reactivity of the antibody was assessed by its interaction with alpha-galactosyl residues on rabbit erythrocytes (RabRBC). The specificity was determined by inhibition experiments with various carbohydrates. The anti-Gal interacts with alpha-galactosyl residues, possibly on glycolipids of human RBC (HuRBC), after removal of membrane proteins by treatment with pronase. In addition, the anti-Gal bind specifically to normal and pathologically senescent HuRBC, suggesting a physiological role for this natural antibody in the aging of RBC. The ubiquitous presence of anti-Gal in high titers throughout life implies a constant antigenic stimulation. In addition to the theoretical interest in the antibody, the study of the anti-Gal reactivity seems to bear immunodiagnostic significance. Decrease in the antibody titer was found to reflect humoral immunodeficiency disorders.","title":"A unique natural human IgG antibody with anti-alpha-galactosyl specificity"},{"docid":"MED-3687","text":"This study was aimed at determining the probiotic potential of a large number of autochthonous lactic acid bacteria isolated from fruit and vegetables. Survival under simulated gastric and intestinal conditions showed that 35% of the strains, mainly belonging to the species Lactobacillus plantarum maintained high cell densities. Selected strains did not affect the immune-mediation by Caco-2 cells. All strains stimulated all 27 immune-mediators by peripheral blood mononuclear cells (PBMC). A significant (P<0.05; P<0.01) increase of the major part of cytokines and growth factors was found. A few chemokines were stimulated. Immune-mediators with pro-inflammatory activity (IL-17, EOTAXIN and IFNγ) were significantly (P<0.01) stimulated by all strains, followed by IL-1b>IP-10>IL-6>MIP1α. Stimulation of IL-12, IL-2 and IL-7 was strain dependent. Only a few strains increased the synthesis of cytokines with anti-inflammatory activity. Six L. plantarum strains were further selected. Four were defined as the strongly adhesive strains (more than 40 bacteria adhering to one Caco-2 cell), and 2 as the adhesive strains (5-40 bacteria adhering to one Caco-2 cell). Five strains grew and acidified chemically defined medium with fructo-oligosaccharides (FOS) as the only carbon source. End-products of FOS fermentation were found. All strains inhibited enterohemorragic Escherichia coli K12 and Bacillus megaterium F6 isolated from human sources. The results of this study showed that some autochthonous lactic acid bacteria from raw fruit and vegetables have functional features to be considered as novel probiotic candidates. Copyright © 2012 Elsevier Ltd. All rights reserved.","title":"Novel probiotic candidates for humans isolated from raw fruits and vegetables."},{"docid":"MED-2203","text":"Constipation is a common health problem that adversely affects quality of life and the prognosis of hospitalized patients with acute coronary syndromes (ACS). The purpose of this study was to develop and test the sweet potato/footbath/acupressure massage (SFA) intervention as a safe treatment for prevention of constipation and to increase satisfaction with bowel emptying in hospitalized patients with ACS. The study was a prospective, randomized controlled trial with a sample of 93 patients (SFA group, n = 44; usual care group, n = 49). Patients in the SFA group received SFA intervention combined with usual care. The results showed that there were statistical differences between the two groups in terms of (1) the incidence of constipation; (2) the use of laxatives and enemas; (3) patients' subjective satisfaction with their bowel emptying during hospitalization; and (4) sensation of incomplete evacuation and anorectal obstruction/blockade. The SFA intervention was more effective, economical, and practical than usual care alone in managing constipation and satisfaction with defecation in patients hospitalized with ACS.","title":"The effect of a sweet potato, footbath, and acupressure intervention in preventing constipation in hospitalized patients with acute coronary syndro..."},{"docid":"MED-2498","text":"Dietary restriction (DR) and reduced growth factor signaling both elevate resistance to oxidative stress, reduce macromolecular damage, and increase lifespan in model organisms. In rodents, both DR and decreased growth factor signaling reduce the incidence of tumors and slow down cognitive decline and aging. DR reduces cancer and cardiovascular disease and mortality in monkeys, and reduces metabolic traits associated with diabetes, cardiovascular disease and cancer in humans. Neoplasias and diabetes are also rare in humans with loss of function mutations in the growth hormone receptor. DR and reduced growth factor signaling may thus slow aging by similar, evolutionarily conserved, mechanisms. We review these conserved anti-aging pathways in model organisms, discuss their link to disease prevention in mammals, and consider the negative side effects that might hinder interventions intended to extend healthy lifespan in humans.","title":"Dietary Restriction, Growth Factors and Aging: from yeast to humans"},{"docid":"MED-3351","text":"Based on evidence that the color red elicits avoidance motivation across contexts (Mehta & Zhu, 2009), two studies investigated the effect of the color red on snack food and soft drink consumption. In line with our hypothesis, participants drank less from a red labeled cup than from a blue labeled cup (Study 1), and ate less snack food from a red plate than from a blue or white plate (Study 2). The results suggest that red functions as a subtle stop signal that works outside of focused awareness and thereby reduces incidental food and drink intake. Copyright © 2012 Elsevier Ltd. All rights reserved.","title":"The color red reduces snack food and soft drink intake."},{"docid":"MED-5239","text":"Epidemiological evidence points to increased dairy and meat consumption, staples of the Western diet, as major risk factors for the development of type 2 diabetes (T2D). This paper presents a new concept and comprehensive review of leucine-mediated cell signaling explaining the pathogenesis of T2D and obesity by leucine-induced over-stimulation of mammalian target of rapamycin complex 1 (mTORC1). mTORC1, a pivotal nutrient-sensitive kinase, promotes growth and cell proliferation in response to glucose, energy, growth factors and amino acids. Dairy proteins and meat stimulate insulin/insulin-like growth factor 1 signaling and provide high amounts of leucine, a primary and independent stimulator for mTORC1 activation. The downstream target of mTORC1, the kinase S6K1, induces insulin resistance by phosphorylation of insulin receptor substrate-1, thereby increasing the metabolic burden of β-cells. Moreover, leucine-mediated mTORC1-S6K1-signaling plays an important role in adipogenesis, thus increasing the risk of obesity-mediated insulin resistance. High consumption of leucine-rich proteins explains exaggerated mTORC1-dependent insulin secretion, increased β-cell growth and β-cell proliferation promoting an early onset of replicative β-cell senescence with subsequent β-cell apoptosis. Disturbances of β-cell mass regulation with increased β-cell proliferation and apoptosis as well as insulin resistance are hallmarks of T2D, which are all associated with hyperactivation of mTORC1. In contrast, the anti-diabetic drug metformin antagonizes leucine-mediated mTORC1 signaling. Plant-derived polyphenols and flavonoids are identified as natural inhibitors of mTORC1 and exert anti-diabetic and anti-obesity effects. Furthermore, bariatric surgery in obesity reduces increased plasma levels of leucine and other branched-chain amino acids. Attenuation of leucine-mediated mTORC1 signaling by defining appropriate upper limits of the daily intake of leucine-rich animal and dairy proteins may offer a great chance for the prevention of T2D and obesity, as well as other epidemic diseases of civilization with increased mTORC1 signaling, especially cancer and neurodegenerative diseases, which are frequently associated with T2D.","title":"Leucine signaling in the pathogenesis of type 2 diabetes and obesity"},{"docid":"MED-3925","text":"This study describes how foods rich in fisetin and hexacosanol added to a strict diet reversed most symptoms of Parkinson's disease (PD) in one patient. This is a case report involving outpatient care. The subject was a dietitian diagnosed with idiopathic PD in 2000 at the age of 53 years old, with a history of exposure to neurotoxins and no family history of PD. A basic diet started in 2000 consisted of predominantly fruits, vegetables, 100% whole grains, extra virgin olive oil, nuts, seeds, nonfat milk products, tea, coffee, spices, small amounts of dark chocolate, and less than 25 g of animal fat daily. The basic diet alone failed to prevent decline due to PD. In 2009, the basic diet was enhanced with a good dietary source of both fisetin and hexacosanol. Six months after the patient started the enhanced diet rich in fisetin and hexacosanol, a clinically significant improvement in symptoms was noted; the patient's attending neurologist reported that the clinical presentation of cogwheel rigidity, micrographia, bradykinesia, dystonia, constricted arm swing with gait, hypomimia, and retropulsion appeared to be resolved. The only worsening of symptoms occurred when the diet was not followed precisely. Little improvement in tremor or seborrhea was observed. The clinical improvement has persisted to date. To the best of our knowledge, this is the first case where adjunctive diet therapy resulted in a significant reduction of symptoms of PD without changing the type or increasing the amount of medications.","title":"A diet low in animal fat and rich in N-hexacosanol and fisetin is effective in reducing symptoms of Parkinson's disease."},{"docid":"MED-3773","text":"The present study assessed the effects of mild dehydration on cognitive performance and mood of young males. A total of twenty-six men (age 20·0 (sd 0·3) years) participated in three randomised, single-blind, repeated-measures trials: exercise-induced dehydration plus a diuretic (DD; 40 mg furosemide); exercise-induced dehydration plus placebo containing no diuretic (DN); exercise while maintaining euhydration plus placebo (EU; control condition). Each trial included three 40 min treadmill walks at 5·6 km/h, 5 % grade in a 27·7°C environment. A comprehensive computerised six-task cognitive test battery, the profile of mood states questionnaire and the symptom questionnaire (headache, concentration and task difficulty) were administered during each trial. Paired t tests compared the DD and DN trials resulting in >1 % body mass loss (mean 1·59 (sd 0·42) %) with the volunteer's EU trial (0·01 (sd 0·03) %). Dehydration degraded specific aspects of cognitive performance: errors increased on visual vigilance (P = 0·048) and visual working memory response latency slowed (P = 0·021). Fatigue and tension/anxiety increased due to dehydration at rest (P = 0·040 and 0·029) and fatigue during exercise (P = 0·026). Plasma osmolality increased due to dehydration (P < 0·001) but resting gastrointestinal temperature was not altered (P = 0·238). In conclusion, mild dehydration without hyperthermia in men induced adverse changes in vigilance and working memory, and increased tension/anxiety and fatigue.","title":"Mild dehydration impairs cognitive performance and mood of men."},{"docid":"MED-3354","text":"The luminance contrast between facial features and facial skin is greater in women than in men, and women's use of make-up enhances this contrast. In black-and-white photographs, increased luminance contrast enhances femininity and attractiveness in women's faces, but reduces masculinity and attractiveness in men's faces. In Caucasians, much of the contrast between the lips and facial skin is in redness. Red lips have been considered attractive in women in geographically and temporally diverse cultures, possibly because they mimic vasodilation associated with sexual arousal. Here, we investigate the effects of lip luminance and colour contrast on the attractiveness and sex typicality (masculinity/femininity) of human faces. In a Caucasian sample, we allowed participants to manipulate the colour of the lips in colour-calibrated face photographs along CIELab L* (light--dark), a* (red--green), and b* (yellow--blue) axes to enhance apparent attractiveness and sex typicality. Participants increased redness contrast to enhance femininity and attractiveness of female faces, but reduced redness contrast to enhance masculinity of men's faces. Lip blueness was reduced more in female than male faces. Increased lightness contrast enhanced the attractiveness of both sexes, and had little effect on perceptions of sex typicality. The association between lip colour contrast and attractiveness in women's faces may be attributable to its association with oxygenated blood perfusion indicating oestrogen levels, sexual arousal, and cardiac and respiratory health.","title":"Lip colour affects perceived sex typicality and attractiveness of human faces."},{"docid":"MED-5197","text":"BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) and heterocyclic amines (HCAs) are carcinogens formed in or on the surface of well-done meat, cooked at high temperature. METHODS: We estimated breast cancer risk in relation to intake of cooked meat in a population-based, case-control study (1508 cases and 1556 controls) conducted in Long Island, NY from 1996 to 1997. Lifetime intakes of grilled or barbecued and smoked meats were derived from the interviewer-administered questionnaire data. Dietary intakes of PAH and HCA were derived from the self-administered modified Block food frequency questionnaire of intake 1 year before reference date. Unconditional logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Modest increased risk was observed among postmenopausal, but not premenopausal, women consuming the most grilled or barbecued and smoked meats over the life course (OR = 1.47; CI = 1.12-1.92 for highest vs. lowest tertile of intake). Postmenopausal women with low fruit and vegetable intake, but high lifetime intake of grilled or barbecued and smoked meats, had a higher OR of 1.74 (CI = 1.20-2.50). No associations were observed with the food frequency questionnaire-derived intake measures of PAHs and HCAs, with the possible exception of benzo(alpha)pyrene from meat among postmenopausal women whose tumors were positive for both estrogen receptors and progesterone receptors (OR = 1.47; CI = 0.99-2.19). CONCLUSIONS: These results support the accumulating evidence that consumption of meats cooked by methods that promote carcinogen formation may increase risk of postmenopausal breast cancer.","title":"Cooked meat and risk of breast cancer--lifetime versus recent dietary intake."},{"docid":"MED-3933","text":"In this study, the effects of a diet rich in insoluble fiber (DRIF) on motor disability and the peripheral pharmacokinetics of orally administered L-dopa in Parkinsonian patients with marked constipation are analyzed. We found a useful effect of a DRIF on plasma L-dopa concentration and motor function. The greatest effect on the plasma L-dopa levels was found early (at 30 and 60 min) after oral administration. There was a relationship between the improvement of constipation and the higher bioavailability of L-dopa. DRIF can be a coadjuvant treatment in patients with Parkinson's disease.","title":"Clinical and pharmacokinetic effects of a diet rich in insoluble fiber on Parkinson disease."},{"docid":"MED-2831","text":"TNFs are major mediators of inflammation and inflammation-related diseases, hence, the United States Food and Drug Administration (FDA) has approved the use of blockers of the cytokine, TNF-α, for the treatment of osteoarthritis, inflammatory bowel disease, psoriasis and ankylosis. These drugs include the chimeric TNF antibody (infliximab), humanized TNF-α antibody (Humira) and soluble TNF receptor-II (Enbrel) and are associated with a total cumulative market value of more than $20 billion a year. As well as being expensive ($15 000–20 000 per person per year), these drugs have to be injected and have enough adverse effects to be given a black label warning by the FDA. In the current report, we describe an alternative, curcumin (diferuloylmethane), a component of turmeric (Curcuma longa) that is very inexpensive, orally bioavailable and highly safe in humans, yet can block TNF-α action and production in in vitro models, in animal models and in humans. In addition, we provide evidence for curcumin's activities against all of the diseases for which TNF blockers are currently being used. Mechanisms by which curcumin inhibits the production and the cell signalling pathways activated by this cytokine are also discussed. With health-care costs and safety being major issues today, this golden spice may help provide the solution. Linked Articles This article is part of a themed section on Emerging Therapeutic Aspects in Oncology. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.169.issue-8","title":"Curcumin: an orally bioavailable blocker of TNF and other pro-inflammatory biomarkers"},{"docid":"MED-2448","text":"A double-blind comparative study was conducted on cedar pollinosis patients in order to evaluate the treatment efficacy of apple polyphenol (Ap). Ap was administered (500 mg) once daily for 12 weeks, starting about 2 weeks prior to cedar pollen dispersion. Pollinosis symptoms during the study were evaluated according to the classification in the guidelines for allergic rhinitis diagnosis and treatment. The results show that the sneezing score was significantly lower for the Ap group than with the placebo group during the early period of pollen dispersion and during the main dispersion period. In addition, no adverse reactions were induced by Ap during the study. These results suggest that Ap may alleviate the symptoms of cedar pollinosis.","title":"Clinical efficacy of apple polyphenol for treating cedar pollinosis."},{"docid":"MED-2365","text":"Twenty-five patients living in a tick-endemic region of Sydney, New South Wales developed red meat allergy after experiencing large local reactions to tick bites. This represents a potentially novel cross-reaction between an arthropod and a food protein. (MJA 2009; 190: 510-511).","title":"An association between tick bite reactions and red meat allergy in humans."},{"docid":"MED-3307","text":"OBJECTIVE: workers in slaughterhouses and processing plants that handle pigs, and pork butchers/meatcutters have been little studied for health risks associated with employment, in spite of the fact that they are potentially exposed to oncogenic and non-oncogenic transmissible agents and chemical carcinogens at work. We report here on an update of mortality in 510 workers employed in abattoirs and processing plants that almost exclusively handled pigs and pork products. METHODS: standardized mortality ratios (SMRs) were estimated for the cohort as a whole, and in subgroups defined by race and sex, using the corresponding US general population mortality rates for comparison. Study subjects were followed up from January 1950 to December 2006, during which time 45% of them died. RESULTS: mortality was significantly increased overall in the cohort. A statistically significant excess of deaths was observed for colon and lung cancers in the entire cohort, SMR=2.7 (95% CI, 1.2-5.1), SMR=1.8 (95% CI, 1.1-2.7), respectively. Significant SMRs in the cohort as a whole were also observed for senile and pre-senile psychotic conditions (SMR=5.1, 95% CI, 1.4-13.1), and pneumonia (SMR=2.6, 95% CI, 1.3-4.8). An observed excess of subarachnoid hemorrhage was seen mainly in whites (SMR=10.1, 95% CI, 1.2-36.3). There was a suggestion of an excess of deaths from ischemic heart disease also, but the elevated SMR was confined to men and was not statistically significant. CONCLUSION: this study confirms the excess occurrence of lung and colon cancers, and stroke previously reported in this occupational group. New findings are the excess of risk for senile and pre-senile psychotic conditions and pneumonia, which together with the excess of colon cancer appear specific for pig/pork workers, as they were not evident in much larger studies of workers in abattoirs and processing plants handling cattle and sheep. However, caution should be exercised in interpreting these findings, since some of them could have occurred by chance, resulting from our examination of a large number of causes of death in multiple study subgroups. For the moment, the significance of these findings remains unknown until they are confirmed in larger studies of adequate statistical power. Studies that will take into account possible occupational and non-occupational confounding factors are needed. Copyright © 2011. Published by Elsevier Inc.","title":"Mortality in workers employed in pig abattoirs and processing plants."},{"docid":"MED-3280","text":"Conventional chemotherapies have showed their limits, notably for patients with advanced cancer. New therapeutic strategies must be identified, and the metabolic abnormalities of cancer cells offer such opportunities. Many human cancer cell lines and primary tumors have absolute requirements for methionine, an essential amino acid. In contrast, normal cells are relatively resistant to exogenous methionine restriction. The biochemical mechanism for methionine dependency has been studied extensively, but the fundamental mechanism remains unclear. A number of investigators have attempted to exploit the methionine dependence of tumors for therapeutic effects in vivo. To reduce in vivo methionine in plasma and tumours, dietary and pharmacological treatments have been used. Methionine-free diet or methionine-deprived total parenteral nutrition causes regression of a variety of animal tumours. Alternatively, methionine depletion was achieved by the use of methioninase. This enzyme specifically degrades methionine and inhibits tumour growth in preclinical models. Because of potential toxicity and quality of life problems, prolonged methionine restriction with diet or with methioninase is not suitable for clinical use. Methionine restriction may find greater application in association with various chemotherapeutic agents. Several preclinical studies have demonstrated synergy between methionine restriction and various cytotoxic chemotherapy drugs. The experimental results accumulated during the last three decades suggest that methionine restriction can become an additional cancer therapeutic strategy, notably in association with chemotherapy.","title":"Methionine dependency and cancer treatment."},{"docid":"MED-3137","text":"A longstanding goal of dietary surveillance has been to estimate the proportion of the population with intakes above or below a target, such as a recommended level of intake. However, until now, statistical methods for assessing the alignment of food intakes with recommendations have been lacking. The purposes of this study were to demonstrate the National Cancer Institute’s method of estimating the distribution of usual intake of foods and determine the proportion of the U.S. population who does not meet federal dietary recommendations. Data were obtained from the 2001–2004 NHANES for 16,338 persons, aged 2 y and older. Quantities of foods reported on 24-h recalls were translated into amounts of various food groups using the MyPyramid Equivalents Database. Usual dietary intake distributions were modeled, accounting for sequence effect, weekend/weekday effect, sex, age, poverty income ratio, and race/ethnicity. The majority of the population did not meet recommendations for all of the nutrient-rich food groups, except total grains and meat and beans. Concomitantly, overconsumption of energy from solid fats, added sugars, and alcoholic beverages (“empty calories”) was ubiquitous. Over 80% of persons age ≥71 y and over 90% of all other sex-age groups had intakes of empty calories that exceeded the discretionary calorie allowances. In conclusion, nearly the entire U.S. population consumes a diet that is not on par with recommendations. These findings add another piece to the rather disturbing picture that is emerging of a nation’s diet in crisis.","title":"Americans Do Not Meet Federal Dietary Recommendations"},{"docid":"MED-4921","text":"BACKGROUND & AIMS: The diagnostic criteria for celiac disease require small-bowel mucosal villous atrophy with crypt hyperplasia (Marsh III). However, mucosal damage develops gradually and patients may evince clinical symptoms before histologic changes appear. Endomysial antibodies are specific in predicting forthcoming villous atrophy. We hypothesized that patients with mild enteropathy but positive endomysial antibodies benefit from a gluten-free diet (GFD) similarly to patients with more severe enteropathy. METHODS: Small-bowel endoscopy together with clinical evaluations was performed in all together 70 consecutive adults with positive endomysial antibodies. Of these, 23 had only mild enteropathy (Marsh I-II) and they were randomized either to continue on a gluten-containing diet or start a GFD. After 1 year, clinical, serologic, and histologic evaluations were repeated. A total of 47 participants had small-bowel mucosal lesions compatible with celiac disease (Marsh III), and these served as disease controls. RESULTS: In the gluten-containing diet group (Marsh I-II) the small-bowel mucosal villous architecture deteriorated in all participants, and the symptoms and abnormal antibody titers persisted. In contrast, in the GFD group (Marsh I-II) the symptoms were alleviated, antibody titers decreased, and mucosal inflammation diminished equally to celiac controls (Marsh III). When the trial was completed, all participants chose to continue on a life-long GFD. CONCLUSIONS: Patients with endomysial antibodies benefit from a GFD regardless of the degree of enteropathy. The diagnostic criteria for celiac disease need re-evaluation: endomysial antibody positivity without atrophy belongs to the spectrum of genetic gluten intolerance, and warrants dietary treatment.","title":"Diagnosing mild enteropathy celiac disease: a randomized, controlled clinical study."},{"docid":"MED-1256","text":"BACKGROUND: Limited consumption of red meat, including beef, is one of many often-suggested strategies to reduce the risk of coronary heart disease (CHD). However, the role that beef consumption specifically plays in promoting adverse changes in the cardiovascular risk factor profile is unclear. OBJECTIVE: A meta-analysis of randomized, controlled, clinical trials (RCTs) was conducted to evaluate the effects of beef, independent of other red and processed meats, compared with poultry and/or fish consumption, on lipoprotein lipids. METHODS: RCTs published from 1950 to 2010 were considered for inclusion. Studies were included if they reported fasting lipoprotein lipid changes after beef and poultry/fish consumption by subjects free of chronic disease. A total of 124 RCTs were identified, and 8 studies involving 406 subjects met the prespecified entry criteria and were included in the analysis. RESULTS: Relative to the baseline diet, mean ± standard error changes (in mg/dL) after beef versus poultry/fish consumption, respectively, were -8.1 ± 2.8 vs. -6.2 ± 3.1 for total cholesterol (P = .630), -8.2 ± 4.2 vs. -8.9 ± 4.4 for low-density lipoprotein cholesterol (P = .905), -2.3 ± 1.0 vs. -1.9 ± 0.8 for high-density lipoprotein cholesterol (P = .762), and -8.1 ± 3.6 vs. -12.9 ± 4.0 mg/dL for triacylglycerols (P = .367). CONCLUSION: Changes in the fasting lipid profile were not significantly different with beef consumption compared with those with poultry and/or fish consumption. Inclusion of lean beef in the diet increases the variety of available food choices, which may improve long-term adherence with dietary recommendations for lipid management. Copyright © 2012 National Lipid Association. Published by Elsevier Inc. All rights reserved.","title":"A meta-analysis of randomized controlled trials that compare the lipid effects of beef versus poultry and/or fish consumption."},{"docid":"MED-4680","text":"OBJECTIVE: To investigate associations between dietary intakes throughout childhood and age at menarche, a possible indicator of future risk of disease, in a contemporary cohort of British girls. DESIGN: Diet was assessed by FFQ at 3 and 7 years of age, and by a 3 d unweighed food diary at 10 years. Age at menarche was categorised as before or after 12 years 8 months, a point close to the median age in this cohort. SETTING: Bristol, South-West England. SUBJECTS: Girls (n 3298) participating in the Avon Longitudinal Study of Parents and Children. RESULTS: Higher energy intakes at 10 years were positively associated with the early occurrence of menarche, but this association was removed on adjusting for body size. Total and animal protein intakes at 3 and 7 years were positively associated with age at menarche ≤12 years 8 months (adjusted OR for a 1 sd increase in protein at 7 years: 1·14 (95 % CI 1·04, 1·26)). Higher PUFA intakes at 3 and 7 years were also positively associated with early occurrence of menarche. Meat intake at 3 and 7 years was strongly positively associated with reaching menarche by 12 years 8 months (OR for menarche in the highest v. lowest category of meat consumption at 7 years: 1·75 (95 % CI 1·25, 2·44)). CONCLUSIONS: These data suggest that higher intakes of protein and meat in early to mid-childhood may lead to earlier menarche. This may have implications for the lifetime risk of breast cancer and osteoporosis.","title":"Diet throughout childhood and age at menarche in a contemporary cohort of British girls."},{"docid":"MED-3244","text":"Diet may represent a modifiable prostate cancer (CaP) risk factor, but a vegetable-based prostate-healthy diet is a major change for most men. We used a ratio of animal:vegetable proteins (A:V ratio) to evaluate whether a comprehensive dietary change was self-sustaining following completion of 11 weekly dietary and cooking classes that integrated mindfulness training (MT). Thirty-six men with recurring CaP were randomized to the intervention or wait-list control. Assessments were at baseline, three months and six months. Of the 17 men randomized to the intervention, 14 completed the requirements. Nineteen were randomized to control and 17 completed requirements. Compared to controls, a significant post-intervention (3 months) decrease in A:V ratio in the intervention group (p=.01) was self-maintained 3 months post-intervention (p=0.049). At each assessment, the A:V ratio was correlated with lycopene, fiber, saturated fat, and dietary cholesterol; four dietary components linked to clinically relevant outcomes in CaP. Change in A:V ratio was also significantly correlated with changes in fiber, saturated fat and dietary cholesterol intake. Participants reported regular MT practice and there was a significant correlation between MT practice and changes in both initiation and maintenance of the change in the A:V ratio. These pilot results provide encouraging evidence for the feasibility of a dietary program that includes MT in supporting dietary change for men with recurrent CaP and invite further study to explore the possible role of MT as a means of supporting both initiation of dietary changes and maintenance of those changes over time.","title":"A Novel Measure of Dietary Change in a Prostate Cancer Dietary Program Incorporating Mindfulness Training"},{"docid":"MED-1230","text":"This study examined the relationship between funding sources and the outcomes of published obesity-related research. A list of funded projects for human nutrition research linking food intake to obesity in 2001-2005 was drawn from two distinct sources: (a) the federal government's semi-public generic commodity promotion or \"checkoff\" programs for Fluid Milk and Dairy and (b) the National Institutes of Health (NIH). The Principal Investigator for each funded project was determined. Published literature by that individual was located using an Ovid MEDLINE and PubMed author search. All articles related to both dairy and obesity were included. Financial sponsorship for each article and article conclusions were classified by independent groups of co-investigators. Seventy-nine relevant articles were included in the study. Of these, 62 were sponsored by the checkoff programs and 17 by the NIH. The study did not find consistent evidence that checkoff-funded projects were more likely to support an obesity prevention benefit from dairy consumption. The study did identify a new research methodology for the investigation of bias by source of sponsorship. Copyright © 2012 Elsevier Inc. All rights reserved.","title":"Relationship between funding sources and outcomes of obesity-related research."},{"docid":"MED-3000","text":"An increased risk for colorectal cancer has been consistently reported for long-time consumption of cooked and processed red meat. This has frequently been attributed to chemical carcinogens arising during the cooking process of meat. Long-time fish or poultry consumption apparently does not increase the risk, although similar or higher concentrations of chemical carcinogens were recorded in their preparation for consumption. The geographic epidemiology of colorectal cancer seems to correspond to regions with a high rate of beef consumption. Countries with a virtual absence of beef in the diet (India) or where preferably lamb or goat meat is consumed (several Arabic countries) reveal low rates of colorectal cancer. In China, pork consumption has a long tradition, with an intermediate colorectal cancer rate. In Japan and Korea, large scale beef and pork imports started after World War II or after the Korean War. A steep rise in colorectal cancer incidence was noted after 1970 in Japan and 1990 in Korea. The consumption of undercooked beef (e.g., shabu-shabu, Korean yukhoe and Japanese yukke) became very popular in both countries. The available data are compatible with the interpretation that a specific beef factor, suspected to be one or more thermoresistant potentially oncogenic bovine viruses (e.g., polyoma-, papilloma- or possibly single-stranded DNA viruses) may contaminate beef preparations and lead to latent infections in the colorectal tract. Preceding, concomitant or subsequent exposure to chemical carcinogens arising during cooking procedures should result in increased risk for colorectal cancer synergistic with these infections. Copyright © 2011 UICC.","title":"Red meat consumption and cancer: reasons to suspect involvement of bovine infectious factors in colorectal cancer."},{"docid":"MED-3274","text":"Objective To determine whether dogs can be trained to identify people with bladder cancer on the basis of urine odour more successfully than would be expected by chance alone. Design Experimental, “proof of principle” study in which six dogs were trained to discriminate between urine from patients with bladder cancer and urine from diseased and healthy controls and then evaluated in tests requiring the selection of one bladder cancer urine sample from six controls. Participants 36 male and female patients (age range 48-90 years) presenting with new or recurrent transitional cell carcinoma of the bladder (27 samples used for training; 9 used for formal testing); 108 male and female controls (diseased and healthy, age range 18-85 years—54 samples used in training; 54 used for testing). Main outcome measure Mean proportion of successes per dog achieved during evaluation, compared with an expected value of 1 in 7 (14%). Results Taken as a group, the dogs correctly selected urine from patients with bladder cancer on 22 out of 54 occasions. This gave a mean success rate of 41% (95% confidence intervals 23% to 58% under assumptions of normality, 26% to 52% using bootstrap methods), compared with 14% expected by chance alone. Multivariate analysis suggested that the dogs' capacity to recognise a characteristic bladder cancer odour was independent of other chemical aspects of the urine detectable by urinalysis. Conclusions Dogs can be trained to distinguish patients with bladder cancer on the basis of urine odour more successfully than would be expected by chance alone. This suggests that tumour related volatile compounds are present in urine, imparting a characteristic odour signature distinct from those associated with secondary effects of the tumour, such as bleeding, inflammation, and infection.","title":"Olfactory detection of human bladder cancer by dogs: proof of principle study"},{"docid":"MED-2469","text":"The intestinal flora is considered to have an impact on the development of the immune system. In the anthroposophic lifestyle, a diet comprising vegetables spontaneously fermented by lactobacilli, and a restrictive use of antibiotics, anti-pyretics and vaccinations, is typical. The aim of this study was to assess the gut flora in infants in relation to certain lifestyle characteristics associated with anthroposophy. Sixty-nine children < 2 years of age with an anthroposophic lifestyle, and 59 infants of a similar age with a traditional lifestyle, were clinically examined and questionnaire replies assessed. Fecal samples were analyzed by bacterial enumeration, bacterial typing through biochemical fingerprinting and by measuring microflora-associated characteristics (MACs). The numbers of colony-forming units (CFU)/g of feces were significantly higher for enterococci and lactic acid bacteria in children who had never been exposed to antibiotics (5.5 x 107 vs. 2.1 x 107; p < 0.001 and 10 x 107 vs. 4.1 x 107; p < 0.01, respectively). Furthermore, the number of enterococci was significantly higher in breastfed and vegetarian infants (p < 0.01). The diversity (Simpson's diversity index) of lactobacilli, as determined by biochemical fingerprinting, was higher in infants born at home than in those born in hospital (p < 0.01). Several MACs were related to specific lifestyle features, and infants with an anthroposophic lifestyle had a higher proportion of acetic acid and a lower proportion of propionic acid in their stool as compared to the control children. In conclusion, lifestyle factors related to the anthroposophic way of life influenced the composition of the gut flora in the infants. These differences may contribute to the lower prevalence of atopic disease previously observed in children in anthroposophic families.","title":"An anthroposophic lifestyle and intestinal microflora in infancy."},{"docid":"MED-3785","text":"PURPOSE: Components of one-carbon metabolism are believed to influence cancer development with suggested mechanisms, including DNA methylation and DNA repair mechanisms. However, few prospective studies have investigated one-carbon metabolism in relation to prostate cancer risk, and the results have been conflicting. The aim of this study was to do a comprehensive investigation of the components of one-carbon metabolism in relation to prostate cancer risk. A panel of seven circulating B vitamins and related metabolites was selected, most of which have not been studied before. MATERIALS AND METHODS: We analyzed plasma concentrations of betaine, choline, cysteine, methionine, methylmalonic acid (MMA), vitamin B2, and vitamin B6 in 561 cases and 1,034 controls matched for age and recruitment date, nested within the population-based Northern Sweden Health and Disease Cohort. Relative risks of prostate cancer were estimated by conditional logistic regression. RESULTS: Positive associations with prostate cancer risk were observed for choline and vitamin B2, and an inverse association was observed for MMA. The relative risks for a doubling in concentrations were 1.46 [95% confidence interval (95% CI), 1.04-2.05; P(trend) = 0.03] for choline, 1.11 (95% CI, 1.00-1.23; P(trend) = 0.04) for vitamin B2, and 0.78 (95% CI, 0.63-0.97; P(trend) = 0.03) for MMA. Concentrations of betaine, cysteine, methionine, and vitamin B6 were not associated with prostate cancer risk. CONCLUSION: The results of this large prospective study suggest that elevated plasma concentrations of choline and vitamin B2 may be associated with an increased risk of prostate cancer. These novel findings support a role of one-carbon metabolism in prostate cancer etiology and warrant further investigation.","title":"One-carbon metabolism and prostate cancer risk: prospective investigation of seven circulating B vitamins and metabolites."},{"docid":"MED-3350","text":"Normotensive adults on low-sodium, weight-loss, and control diets recorded preferences and perceived saltiness for sodium chloride (NaCl) added to cream soup at intervals over 1 yr. Reduction in sodium intake and excretion accompanied a shift in preference toward less salt: preferred concentrations by ad libitum salting declined from 0.72% at the onset to 0.33% NaCl at week 24; hedonic scores for high concentrations of NaCl decreased significantly while scores for low concentrations increased. After 3 mo of sodium restriction, NaCl preferences readjusted to a lower level: ad libitum additions of NaCl were similar after 13, 24, and 52 wk. Less hedonic variation was observed among controls than among Na-restricted groups. The weight-loss group showed increased liking for mid-range NaCl levels. Mechanisms underlying preference changes, including physiological, behavioral, and context effects, may provide insights into maintenance of low-sodium diets for treatment and prevention of hypertension.","title":"Effect of dietary sodium restriction on taste responses to sodium chloride: a longitudinal study."},{"docid":"MED-1720","text":"BACKGROUND: Insulin-like growth factor (IGF)-I and its main binding protein, IGFBP-3, modulate cell growth and survival, and are thought to be important in tumour development. Circulating concentrations of IGF-I might be associated with an increased risk of cancer, whereas IGFBP-3 concentrations could be associated with a decreased cancer risk. METHODS: We did a systematic review and meta-regression analysis of case-control studies, including studies nested in cohorts, of the association between concentrations of IGF-I and IGFBP-3 and prostate, colorectal, premenopausal and postmenopausal breast, and lung cancer. Study-specific dose-response slopes were obtained by relating the natural log of odds ratios for different exposure levels to blood concentrations normalised to a percentile scale. FINDINGS: We identified 21 eligible studies (26 datasets), which included 3609 cases and 7137 controls. High concentrations of IGF-I were associated with an increased risk of prostate cancer (odds ratio comparing 75th with 25th percentile 1.49, 95% CI 1.14-1.95) and premenopausal breast cancer (1.65, 1.26-2.08) and high concentrations of IGFBP-3 were associated with increased risk of premenopausal breast cancer (1.51, 1.01-2.27). Associations were larger in assessments of plasma samples than in serum samples, and in standard case-control studies compared with nested studies. INTERPRETATION: Circulating concentrations of IGF-I and IGFBP-3 are associated with an increased risk of common cancers, but associations are modest and vary between sites. Although laboratory methods need to be standardised, these epidemiological observations could have major implications for assessment of risk and prevention of cancer.","title":"Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis."},{"docid":"MED-2517","text":"Many experts in the biology of ageing believe that pharmacological interventions to slow ageing are a matter of ‘when’ rather than ‘if’. A leading target for such interventions is the nutrient response pathway defined by the mechanistic target of rapamycin (mTOR). Inhibition of this pathway extends lifespan in model organisms and confers protection against a growing list of age-related pathologies. Characterized inhibitors of this pathway are already clinically approved, and others are under development. Although adverse side effects currently preclude use in otherwise healthy individuals, drugs that target the mTOR pathway could one day become widely used to slow ageing and reduce age-related pathologies in humans.","title":"mTOR is a key modulator of ageing and age-related disease"},{"docid":"MED-4831","text":"Dyslipidemia is a primary risk factor for cardiovascular disease, peripheral vascular disease, and stroke. Current guidelines recommend diet as first-line therapy for patients with elevated plasma cholesterol concentrations. However, what constitutes an optimal dietary regimen remains a matter of controversy. Large prospective trials have demonstrated that populations following plant-based diets, particularly vegetarian and vegan diets, are at lower risk for ischemic heart disease mortality. The investigators therefore reviewed the published scientific research to determine the effectiveness of plant-based diets in modifying plasma lipid concentrations. Twenty-seven randomized controlled and observational trials were included. Of the 4 types of plant-based diets considered, interventions testing a combination diet (a vegetarian or vegan diet combined with nuts, soy, and/or fiber) demonstrated the greatest effects (up to 35% plasma low-density lipoprotein cholesterol reduction), followed by vegan and ovolactovegetarian diets. Interventions allowing small amounts of lean meat demonstrated less dramatic reductions in total cholesterol and low-density lipoprotein levels. In conclusion, plant-based dietary interventions are effective in lowering plasma cholesterol concentrations.","title":"Effects of plant-based diets on plasma lipids."},{"docid":"MED-3143","text":"BACKGROUND: Olestra is a nonabsorbable, energy-free fat substitute. Because it is not absorbed, it may cause digestive symptoms when consumed in large amounts. OBJECTIVE: To compare the frequency and impact of gastrointestinal symptoms in adults and children who freely consume snacks containing olestra or regular snacks in the home. DESIGN: 6-week, double-blind, randomized, parallel, placebo-controlled trial. SETTING: General community. PARTICIPANTS: 3181 volunteers 2 to 89 years of age. INTERVENTION: Households received identical packages labeled as containing olestra corn or potato chips. These packages contained either olestra or regular chips (control). MEASUREMENT: Gastrointestinal symptoms and their impact on daily activities were reported in a daily record. RESULTS: At least one gastrointestinal symptom was reported by 619 of 1620 (38.2%) persons in the olestra group and 576 of 1561 (36.9%) controls (difference, 1.3 percentage points [95% CI, -3.6 to 6.2 percentage points]; P = 0.60). In general, the groups did not differ significantly in the proportion of participants who reported individual gastrointestinal symptoms; however, more controls reported nausea (8.4% compared with 5.7%; difference, -2.7 percentage points [CI, -4.9 to -0.4 percentage points]; P = 0.02). The only difference between groups for the mean numbers of days on which symptoms were reported was that participants in the olestra group had 1 more symptom-day of more frequent bowel movements than did controls (3.7 symptom-days compared with 2.8 symptom days; difference, 0.9 symptom-days [CI, 0.1 to 1.8 symptom-days]; P = 0.04). The groups did not differ in the impact of symptoms on daily activities. CONCLUSIONS: Clinically meaningful or bothersome gastrointestinal effects are not associated with unregulated consumption of olestra corn and potato chips in the home.","title":"Gastrointestinal symptoms in 3181 volunteers ingesting snack foods containing olestra or triglycerides. A 6-week randomized, placebo-controlled trial."},{"docid":"MED-4261","text":"BACKGROUND: Meat intake may be related to weight gain because of its high energy and fat content. Some observational studies have shown that meat consumption is positively associated with weight gain, but intervention studies have shown mixed results. OBJECTIVE: Our objective was to assess the association between consumption of total meat, red meat, poultry, and processed meat and weight gain after 5 y of follow-up, on average, in the large European population who participated in the European Prospective Investigation into Cancer and Nutrition-Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating Out of Home and Obesity (EPIC-PANACEA) project. DESIGN: A total of 103,455 men and 270,348 women aged 25-70 y were recruited between 1992 and 2000 in 10 European countries. Diet was assessed at baseline with the use of country-specific validated questionnaires. A dietary calibration study was conducted in a representative subsample of the cohort. Weight and height were measured at baseline and self-reported at follow-up in most centers. Associations between energy from meat (kcal/d) and annual weight change (g/y) were assessed with the use of linear mixed models, controlled for age, sex, total energy intake, physical activity, dietary patterns, and other potential confounders. RESULTS: Total meat consumption was positively associated with weight gain in men and women, in normal-weight and overweight subjects, and in smokers and nonsmokers. With adjustment for estimated energy intake, an increase in meat intake of 250 g/d (eg, one steak at approximately 450 kcal) would lead to a 2-kg higher weight gain after 5 y (95% CI: 1.5, 2.7 kg). Positive associations were observed for red meat, poultry, and processed meat. CONCLUSION: Our results suggest that a decrease in meat consumption may improve weight management.","title":"Meat consumption and prospective weight change in participants of the EPIC-PANACEA study."},{"docid":"MED-2830","text":"OBJECTIVE: The aim of this work was to determine the bioavailability of herbs and spices after human consumption by measuring the ability to protect lymphocytes from an oxidative injury and by examining the impact on inflammatory biomarkers in activated THP-1 cells. METHODS: Ten to 12 subjects in each of 13 groups consumed a defined amount of herb or spice for 7 days. Blood was drawn from subjects before consumption and 1 hour after taking the final herb or spice capsules. Subject serum and various extractions of the herbs and spices were analyzed for antioxidant capacity by oxygen radical absorbance capacity (ORAC) analysis or by 1,1-diphenyl-2-picrylhydrzyl (DPPH). Subject peripheral blood mononuclear cells (PBMCs) in medium with10% autologous serum were incubated with hydrogen peroxide to induce DNA strand breaks. Subject serum was also used to treat activated THP-1 cells to determine relative quantities of 3 inflammatory cytokine (tumor necrosis factor-α [TNF-α], interleukin-1α [IL-1α], and IL-6) mRNAs. RESULTS: Herbs and spices that protected PBMCs against DNA strand breaks were paprika, rosemary, ginger, heat-treated turmeric, sage, and cumin. Paprika also appeared to protect cells from normal apoptotic processes. Of the 3 cytokine mRNAs studied (TNF-α, IL-1α, and IL-6), TNF-α was the most sensitive responder to oxidized LDL-treated macrophages. Clove, ginger, rosemary, and turmeric were able to significantly reduce oxidized LDL-induced expression of TNF-α. Serum from those consuming ginger reduced all three inflammatory biomarkers. Ginger, rosemary, and turmeric showed protective capacity by both oxidative protection and inflammation measures. CONCLUSIONS: DNA strand breaks and inflammatory biomarkers are a good functional measure of a food's bioavailability.","title":"Bioavailability of herbs and spices in humans as determined by ex vivo inflammatory suppression and DNA strand breaks."},{"docid":"MED-2209","text":"This study investigated the effect of different traditional cooking methods on glycemic index (GI) and glycemic response of ten Sweet potato (Ipomoea batatas) cultivars commonly eaten in Jamaica. Matured tubers were cooked by roasting, baking, frying, or boiling then immediately consumed by the ten nondiabetic test subjects (5 males and 5 females; mean age of 27 ± 2 years). The GI varied between 41 ± 5–93 ± 5 for the tubers studied. Samples prepared by boiling had the lowest GI (41 ± 5–50 ± 3), while those processed by baking (82 ± 3–94 ± 3) and roasting (79 ± 4–93 ± 2) had the highest GI values. The study indicates that the glycemic index of Jamaican sweet potatoes varies significantly with the method of preparation and to a lesser extent on intravarietal differences. Consumption of boiled sweet potatoes could minimize postprandial blood glucose spikes and therefore, may prove to be more efficacious in the management of type 2 diabetes mellitus.","title":"Relationship between Processing Method and the Glycemic Indices of Ten Sweet Potato (Ipomoea batatas) Cultivars Commonly Consumed in Jamaica"},{"docid":"MED-3242","text":"Previous studies have suggested that dietary factors may be important in the development of bladder cancer. We examined macronutrient intake in relation to risk of urothelial cell carcinoma among 469,339 men and women in the European Prospective Investigation into Cancer and Nutrition. Associations were examined using Cox regression, stratified by sex, age at recruitment and centre and further adjusted for smoking status and duration, body mass index and total energy intake. After an average of 11.3 years of follow-up, 1,416 new cases of urothelial cell carcinoma were identified. After allowing for measurement error, a 3% increase in the consumption of energy intake from animal protein was associated with a 15% higher risk (95% confidence interval [CI]: 3-30%; p(trend) = 0.01) and a 2% increase in energy from plant protein intake was associated with a 23% lower risk (95% CI: 36-7%, p(trend) = 0.006). Dietary intake of fat, carbohydrate, fibre or calcium was not associated with risk. These findings suggest that animal and/or plant protein may affect the risk of urothelial cell carcinoma, and examination of these associations in other studies is needed. Copyright © 2012 UICC.","title":"Macronutrient intake and risk of urothelial cell carcinoma in the European prospective investigation into cancer and nutrition."},{"docid":"MED-4258","text":"The objective of the present study was to assess animal and plant protein intakes in the Belgian population and to examine their relationship with overweight and obesity (OB). The subjects participated in the Belgian National Food Consumption Survey conducted in 2004. Food consumption was assessed by using two non-consecutive 24 h dietary recalls. About 3083 participants ( ≥ 15 years of age; 1546 males, 1537 females) provided completed dietary information. Animal protein intake (47 g/d) contributed more to total protein intakes of 72 g/d than plant protein intake, which accounted for 25 g/d. Meat and meat products were the main contributors to total animal protein intakes (53 %), whereas cereals and cereal products contributed most to plant protein intake (54 %). Males had higher animal and plant protein intakes than females (P < 0·001). Legume and soya protein intakes were low in the whole population (0·101 and 0·174 g/d, respectively). In males, animal protein intake was positively associated with BMI (β = 0·013; P = 0·001) and waist circumference (WC; β = 0·041; P = 0·002). Both in males and females, plant protein intake was inversely associated with BMI (males: β = - 0·036; P < 0·001; females: β = - 0·046; P = 0·001) and WC (male: β = - 0·137; P < 0·001; female: β = - 0·096; P = 0·024). In conclusion, plant protein intakes were lower than animal protein intakes among a representative sample of the Belgian population and decreased with age. Associations with anthropometric data indicated that plant proteins could offer a protective effect in the prevention of overweight and OB in the Belgian population.","title":"Plant and animal protein intake and its association with overweight and obesity among the Belgian population."},{"docid":"MED-3455","text":"Exercise-induced deoxyribonucleic acid (DNA) damage is often associated with an increase in free radicals; however, there is a lack of evidence examining the two in parallel. This study tested the hypothesis that high-intensity exercise has the ability to produce free radicals that may be capable of causing DNA damage. Twelve apparently healthy male subjects (age: 23 ± 4 years; stature: 181 ± 8 cm; body mass: 80 ± 9 kg; and VO(2max) : 49 ± 5 ml/kg/min) performed three 5 min consecutive and incremental stages (40, 70, and 100% of VO(2max) ) of aerobic exercise with a 15-min period separating each stage. Blood was drawn after each bout of exercise for the determination of ex vivo free radicals, DNA damage, protein carbonyls, lipid hydroperoxide (LOOH) concentration, and a range of lipid-soluble antioxidants. Lipid-derived oxygen-centered free radicals (hyperfine coupling constants a(Nitrogen) = 13.7 Gauss (G) and aβ(Hydrogen) = 1.8 G) increased as a result of acute moderate and high-intensity exercise (P < 0.05), while DNA damage was also increased (P < 0.05). Systemic changes were observed in LOOH and for lipid-soluble antioxidants throughout exercise (P < 0.05); however, there was no observed change in protein carbonyl concentration (P > 0.05). These findings identify lipid-derived free radical species as possible contributors to peripheral mononuclear cell DNA damage in the human exercising model. This damage occurs in the presence of lipid oxidation but in the absence of any change to protein carbonyl concentration. The significance of these findings may have relevance in terms of immune function, the aging process, and the pathology of carcinogenesis. Copyright © 2010 Wiley-Liss, Inc.","title":"Exercise-induced lipid peroxidation: Implications for deoxyribonucleic acid damage and systemic free radical generation."},{"docid":"MED-4049","text":"More than 85% of breast cancers are sporadic and attributable to long-term exposure to environmental carcinogens, such as those in the diet, through a multistep disease process progressing from non-cancerous to premalignant and malignant stages. The chemical carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is one of the most abundant heterocyclic amines found in high-temperature cooked meats and is recognized as a mammary carcinogen. However, the PhIP’s mechanism of action in breast cell carcinogenesis is not clear. Here, we demonstrated, for the first time, that cumulative exposures to PhIP at physiologically achievable, pico to nanomolar concentrations effectively induced progressive carcinogenesis of human breast epithelial MCF10A cells from a non-cancerous stage to premalignant and malignant stages in a dose- and exposure-dependent manner. Progressive carcinogenesis was measured by increasingly- acquired cancer-associated properties of reduced dependence on growth factors, anchorage-independent growth, acinar-conformational disruption, proliferation, migration, invasion, tumorigenicity with metastasis and increased stem-like cell populations. These biological changes were accompanied by biochemical and molecular changes, including upregulated H-Ras gene expression, extracellular signal-regulated kinase (ERK) pathway activation, Nox-1 expression, reactive oxygen species (ROS) elevation, increased HIF-1α, Sp1, tumor necrosis factor-α, matrix metalloproteinase (MMP)-2, MMP-9, aldehyde dehydrogenase activity and reduced E-cadherin. The Ras-ERK-Nox-ROS pathway played an important role in not only initiation but also maintenance of cellular carcinogenesis induced by PhIP. Using biological, biochemical and molecular changes as targeted endpoints, we identified that the green tea catechin components epicatechin-3-gallate and epigallocatechin-3-gallate, at non-cytotoxic doses, were capable of suppressing PhIP-induced cellular carcinogenesis and tumorigenicity.","title":"Intervention of human breast cell carcinogenesis chronically induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine"},{"docid":"MED-3273","text":"Recent studies confirm that dietary methionine restriction increases both mean and maximal lifespan in rats and mice, achieving \"aging retardant\" effects very similar to those of caloric restriction, including a suppression of mitochondrial superoxide generation. Although voluntary caloric restriction is never likely to gain much popularity as a pro-longevity strategy for humans, it may be more feasible to achieve moderate methionine restriction, in light of the fact that vegan diets tend to be relatively low in this amino acid. Plant proteins - especially those derived from legumes or nuts - tend to be lower in methionine than animal proteins. Furthermore, the total protein content of vegan diets, as a function of calorie content, tends to be lower than that of omnivore diets, and plant protein has somewhat lower bioavailability than animal protein. Whole-food vegan diets that moderate bean and soy intake, while including ample amounts of fruit and wine or beer, can be quite low in methionine, while supplying abundant nutrition for health (assuming concurrent B12 supplementation). Furthermore, low-fat vegan diets, coupled with exercise training, can be expected to promote longevity by decreasing systemic levels of insulin and free IGF-I; the latter effect would be amplified by methionine restriction - though it is not clear whether IGF-I down-regulation is the sole basis for the impact of low-methionine diets on longevity in rodents.","title":"The low-methionine content of vegan diets may make methionine restriction feasible as a life extension strategy."},{"docid":"MED-3359","text":"Background Fruit and vegetable consumption and ingestion of carotenoids have been found to be associated with human skin-color (yellowness) in a recent cross-sectional study. This carotenoid-based coloration contributes beneficially to the appearance of health in humans and is held to be a sexually selected cue of condition in other species. Methodology and Principal Findings Here we investigate the effects of fruit and vegetable consumption on skin-color longitudinally to determine the magnitude and duration of diet change required to change skin-color perceptibly. Diet and skin-color were recorded at baseline and after three and six weeks, in a group of 35 individuals who were without makeup, self-tanning agents and/or recent intensive UV exposure. Six-week changes in fruit and vegetable consumption were significantly correlated with changes in skin redness and yellowness over this period, and diet-linked skin reflectance changes were significantly associated with the spectral absorption of carotenoids and not melanin. We also used psychophysical methods to investigate the minimum color change required to confer perceptibly healthier and more attractive skin-coloration. Modest dietary changes are required to enhance apparent health (2.91 portions per day) and attractiveness (3.30 portions). Conclusions Increased fruit and vegetable consumption confers measurable and perceptibly beneficial effects on Caucasian skin appearance within six weeks. This effect could potentially be used as a motivational tool in dietary intervention.","title":"You Are What You Eat: Within-Subject Increases in Fruit and Vegetable Consumption Confer Beneficial Skin-Color Changes"},{"docid":"MED-2656","text":"The aim of previous research into the causes of allergic diseases, including asthma was mostly to identify potential risk factors in the environment. No major risk factors have been identified, however. Over the past 10 years, focus has, therefore, more been directed towards protective factors that could enhance the development of tolerance to allergens which were previously encountered early in life, but are now lost in modern affluent societies. In particular, the role of childhood infections has been discussed, but so far these studies have not been conclusive. Recent epidemiological studies and experimental research suggest that the microbial environment and exposure to microbial products in infancy modifies immune responses and enhances the development of tolerance to ubiquitous allergens. The intestinal microflora may play a particular role in this respect, as it is the major external driving force in the maturation of the immune system after birth, and animal experiments have shown it to be a prerequisite for normal development of oral tolerance. Recent studies have shown differences in the composition of the microflora between healthy and allergic infants in countries with a high and low prevalence of allergies and between healthy and allergic infants within such countries. These differences are apparent within the first week of life and thus precede clinical symptoms. The use of live microorganisms that might be beneficial to health has a long tradition and the safety is well documented. Very recently, several prospective intervention studies, modifying the gut flora from birth have yielded encouraging results and may suggest a new mode of primary prevention of allergy in the future.","title":"Effects of intestinal microflora and the environment on the development of asthma and allergy."},{"docid":"MED-3535","text":"Cherries, and in particular sweet cherries, are a nutritionally dense food rich in anthocyanins, quercetin, hydroxycinnamates, potassium, fiber, vitamin C, carotenoids, and melatonin. UV concentration, degree of ripeness, postharvest storage conditions, and processing, each can significantly alter the amounts of nutrients and bioactive components. These constituent nutrients and bioactive food components support the potential preventive health benefits of cherry intake in relation to cancer, cardiovascular disease, diabetes, inflammatory diseases, and Alzheimer's disease. Mechanistically, cherries exhibit relatively high antioxidant activity, low glycemic response, COX 1 and 2 enzyme inhibition, and other anti-carcinogenic effects in vitro and in animal experiments. Well-designed cherry feeding studies are needed to further substantiate any health benefits in humans.","title":"Cherries and health: a review."},{"docid":"MED-3876","text":"BACKGROUND: Chinese men have lower incidences of prostate cancer compared to men from Europe and North America. Asians consume large quantities of soya, a rich source of isoflavanoids phyto-oestrogens and have high plasma and urinary levels of these compounds. The mammalian lignans, enterolactone and enterodiol, are another group of weak plant oestrogens and are derived from seeds, cereals and grains. Vegetarians have high plasma and urinary concentrations of lignans. METHODS: The concentrations lignans and isoflavonic phyto-oestrogens were determined by gas chromatography-mass spectrometry (GC-MS) in plasma and prostatic fluid from Portuguese, Chinese and British men consuming their traditional diets. RESULTS: In prostatic fluid the mean concentrations of enterolactone were 31, 162 and 20.3 ng/ml for Hong Kong, Portugal and Britain respectively. Very high levels of enterolactone (> 600 ng/ml) were observed in the prostatic fluid of some of the men from Portugal. High concentrations of equol (3270 ng/ml) and daidzein (532 ng/ml) were found in a sample of prostatic fluid from Hong Kong. Higher mean levels of daidzein were observed in prostatic fluid from Hong Kong at 70 ng/ml, compared to 4.6 and 11.3 ng/ml in samples from Portugal and Britain respectively. Mean levels of daidzein were higher in the plasma samples from Hong Kong (31.3 ng/ml) compared to those from Portugal (1.3 ng/ml) and Britain (8.2 ng/ml). In general, the mean plasma concentrations of enterolactone from the three centres were similar, at 6.2, 3.9 and 3.9 ng/ml in samples from Hong Kong Portugal and Britain respectively. CONCLUSIONS: Higher concentrations of the isoflavanoid phyto-oestrogens, daidzein and equol, were found in the plasma and prostatic fluid of men from Hong Kong compared to those from Britain and Portugal. However, the levels of the lignan, enterolactone, were very much higher in prostatic fluid of Portuguese men. Isoflavanoids and lignans have many interesting properties and may, in part, be responsible for lower incidences of prostate cancer in men from Asia and also some Mediterranean countries. The isoflavanoids from soya, which are present in high concentrations in the prostatic fluid of Asian men, may be protective against prostate disease.","title":"Lignans and isoflavonoids in plasma and prostatic fluid in men: samples from Portugal, Hong Kong, and the United Kingdom."},{"docid":"MED-2513","text":"Over the last several years, new evidence has kept pouring in about the remarkable effect of caloric restriction (CR) on the conspicuous bedfellows- aging and cancer. Through the use of various animal models, it is now well established that by reducing calorie intake one can not only increase life span but, also, lower the risk of various age related diseases such as cancer. Cancer cells are believed to be more dependent on glycolysis for their energy requirements than normal cells and, therefore, can be easily targeted by alteration in the energy-metabolic pathways, a hallmark of CR. Apart from inhibiting the growth of transplantable tumors, CR has been also shown to inhibit the development of spontaneous, radiation, and chemically induced tumors. The question regarding the potentiality of the anti-tumor effect of CR in humans has been in part answered by the resistance of a cohort of women, who had suffered from anorexia in their early life, to breast cancer. However, human research on the beneficial effect of CR is still at an early stage and needs further validation. Though the complete mechanism of the anti-tumor effect of CR is far from clear, the plausible involvement of nutrient sensing pathways or IGF-1 pathways proposed for its anti-aging action cannot be overruled. In fact, cancer cell lines, mutant for proteins involved in IGF-1 pathways, failed to respond to CR. In addition, CR decreases the levels of many growth factors, anabolic hormones, inflammatory cytokines, and oxidative markers that are deregulated in several cancers. In this review, we discuss the anti-tumor effect of CR, describing experiments done in vitro in tumor models and in vivo in mouse models in which the tumor was induced by means of radiation or chemical exposure, expressing oncogenes or deleting tumor suppression genes. We also discuss the proposed mechanisms of CR anti-tumor action. Lastly, we argue the necessity of gene expression studies in cancerous versus normal cells upon CR.","title":"Insights into the beneficial effect of caloric/ dietary restriction for a healthy and prolonged life"},{"docid":"MED-3141","text":"OBJECTIVE: To evaluate the associations with chronic disease risk and mortality of the consequences of bean-free diets in Taiwanese adults with regard to gender. DESIGN: A sub-sample of the National Health Interview Survey (NHIS) in 2001 agreed to physical examination in the subsequent year. This group then took part in the Taiwanese Survey of Hyperglycaemia, Hyperlipidaemia and Hypertension (TwSHHH) in 2002. SETTING: Individual records were linked to the eventual death files from 2002 to 2008. SUBJECTS: Up to the end of 2008, a total of 2820 men and 2950 women were tracked by death registry over the 6·8 years of follow-up. RESULTS: Among 38,077 person-years, an average follow-up 6·5 years, 225 all-cause deaths were identified. Generalized linear models showed beans to be favourable for metabolic syndrome (other than for fasting glucose) in men; in women, beans were favourable for waist circumference and HbA1c. Cumulative logistic regression models for the effect of a bean-free diet on metabolic syndrome scores according to the Taiwanese-modified National Cholesterol Education Program-Adult Treatment Panel III (NCEP-tw) gave adjusted odds ratios of 1·83 in men and 1·45 in women. Cox regression models for the bean-free diet showed an increased hazard ratio for all-cause mortality among women (1·98, 95% CI 1·03, 3·81) but not men (1·28, 95% CI 0·76, 2·16). CONCLUSIONS: A bean-free diet may play a role in developing the metabolic syndrome in both genders, and is a significant predictor of all-cause mortality in Taiwanese women but not men.","title":"A bean-free diet increases the risk of all-cause mortality among Taiwanese women: the role of the metabolic syndrome."},{"docid":"MED-3281","text":"INTRODUCTION: Amino acid auxotrophy or the metabolic defect which renders cancer incapable of surviving under amino acid depleted conditions is being exploited and explored as a therapeutic against cancer. Early clinical data on asparagine- and arginine-depleting drugs have demonstrated low toxicity and efficacy in melanoma, hepatocellular carcinoma and acute lymphoblastic leukemia. Methionine auxotrophy is a novel niche currently under exploration for targeting certain cancers. AREAS COVERED: In this review we explore the discovery of methionine auxotrophy followed by in vitro, in vivo and patient data on targeting cancer with methionine depletion. We end with a small discussion on bioengineering, pegylation and red blood cell encapsulation as mechanisms for decreasing immunogenicity of methionine-depleting drugs. We hope to provide a platform for future pharmacology, toxicology and cytotoxicity studies with methionine depletion therapy and drugs. EXPERT OPINION: Although methionine auxotrophy seems as a viable target, extensive research addressing normal versus cancer cell toxicity needs to be conducted. Further research also needs to be conducted into the molecular mechanism associated with methionine depletion therapy. Finally, novel methods need to be developed to decrease the immunogenicity of methionine-depleting drugs, a current issue with protein therapeutics.","title":"Targeting methionine auxotrophy in cancer: discovery & exploration."},{"docid":"MED-3874","text":"Background Prostate cancer affects one-out-of-six men during their lifetime. Dietary factors are postulated to influence the development and progression of prostate cancer. Low-fat diets and flaxseed supplementation may offer potentially protective strategies. Methods We undertook a multi-site, randomized controlled trial to test the effects of low-fat and/or flaxseed-supplemented diets on the biology of the prostate and other biomarkers. Prostate cancer patients (n=161) scheduled at least 21 days before prostatectomy were randomly assigned to one of the following arms: 1) control (usual diet); 2) flaxseed-supplemented diet (30 g/day); 2) low-fat diet (<20% total energy); or 4) flaxseed-supplemented, low-fat diet. Blood was drawn at baseline and prior to surgery and analyzed for prostate specific antigen (PSA), sex hormone binding globulin, testosterone, insulin-like growth factor-1 and binding protein-3, c-reactive protein, and total and low density lipoprotein cholesterol. Tumors were assessed for proliferation (Ki-67, the primary endpoint) and apoptosis. Results Men were on protocol an average of 30 days. Proliferation rates were significantly lower (P < 0.002) among men assigned to the flaxseed arms. Median Ki-67 positive cells/total nuclei ratios (x100) were 1.66 (flaxseed-supplemented diet) and 1.50 (flaxseed-supplemented, low-fat diet) vs. 3.23 (control) and 2.56 (low-fat diet). No differences were observed between arms with regard to side effects, apoptosis, and most serological endpoints; however, men on low-fat diets experienced significant decreases in serum cholesterol (P=0.048). Conclusions Findings suggest that flaxseed is safe, and associated with biologic alterations that may be protective for prostate cancer. Data also further support low-fat diets to manage serum cholesterol.","title":"Flaxseed Supplementation (not Dietary Fat Restriction) Reduces Prostate Cancer Proliferation Rates in Men Presurgery"},{"docid":"MED-4050","text":"Green tea is a commonly consumed beverage in Asia and has been suggested to have anti-inflammatory and possible anti-carcinogenic properties in laboratory studies. We sought to examine the association between green tea consumption and risk of breast cancer incidence or recurrence, using all available epidemiologic evidence to date. We conducted a systematic search of five databases and performed a meta-analysis of studies of breast cancer risk and recurrence published between 1998 and 2009, encompassing 5,617 cases of breast cancer. Summary relative risks (RR) were calculated using a fixed effects model, and tests of heterogeneity across combined studies were conducted. We identified two studies of breast cancer recurrence and seven studies of breast cancer incidence. Increased green tea consumption (more than three cups a day) was inversely associated with breast cancer recurrence (Pooled RR = 0.73, 95% CI: 0.56-0.96). An analysis of case-control studies of breast cancer incidence suggested an inverse association with a pooled RR of 0.81 (95% CI: 0.75, 0.88) while no association was found among cohort studies of breast cancer incidence. Combining all studies of breast cancer incidence resulted in significant heterogeneity. Available epidemiologic evidence supports the hypothesis that increased green tea consumption may be inversely associated with risk of breast cancer recurrence. The association between green tea consumption and breast cancer incidence remains unclear based on the current evidence.","title":"Green tea consumption and breast cancer risk or recurrence: a meta-analysis."},{"docid":"MED-3197","text":"Background: A Step I diet with lean beef compared with lean white meat both decrease LDL cholesterol. To our knowledge, no studies have evaluated a low–saturated fatty acid (SFA) (<7% calories) diet that contains lean beef. Objective: We studied the effect on LDL cholesterol of cholesterol-lowering diets with varying amounts of lean beef [ie, Dietary Approaches to Stop Hypertension (DASH): 28 g beef/d; Beef in an Optimal Lean Diet (BOLD): 113 g beef/d; and Beef in an Optimal Lean Diet plus additional protein (BOLD+): 153 g beef/d] compared with that of a healthy American diet (HAD). Design: Thirty-six hypercholesterolemic participants (with LDL-cholesterol concentrations >2.8 mmol/L) were randomly assigned to consume each of the 4 diets (HAD: 33% total fat, 12% SFA, 17% protein, and 20 g beef/d), DASH (27% total fat, 6% SFA, 18% protein, and 28 g beef/d), BOLD (28% total fat, 6% SFA, 19% protein, and 113 g beef/d), and BOLD+ (28% total fat, 6% SFA, 27% protein, and 153 g beef/d) for 5 wk. Results: There was a decrease in total cholesterol (TC) and LDL-cholesterol concentrations (P < 0.05) after consumption of the DASH (−0.49 ± 0.11 and −0.37 ± 0.09 mmol/L, respectively), BOLD (−0.48 ± 0.10 and −0.35 ± 0.9 mmol/L, respectively), and BOLD+ (−0.50 ± 0.10 and −0.345 ± 0.09 mmol/L, respectively) diets compared with after consumption of the HAD (−0.22 ± 0.10 and −0.14 ± 0.10 mmol/L, respectively). Apolipoprotein A-I, C-III, and C-III bound to apolipoprotein A1 particles decreased after BOLD and BOLD+ diets compared with after the HAD, and there was a greater decrease in apolipoprotein B after consumption of the BOLD+ diet than after consumption of the HAD (P < 0.05 for both). LDL cholesterol and TC decreased after consumption of the DASH, BOLD, and BOLD+ diets when the baseline C-reactive protein (CRP) concentration was <1 mg/L; LDL cholesterol and TC decreased when baseline CRP concentration was >1 mg/L with the BOLD and BOLD+ diets. Conclusions: Low-SFA, heart-healthy dietary patterns that contain lean beef elicit favorable effects on cardiovascular disease (CVD) lipid and lipoprotein risk factors that are comparable to those elicited by a DASH dietary pattern. These results, in conjunction with the beneficial effects on apolipoprotein CVD risk factors after consumption of the BOLD and BOLD+ diets, which were greater with the BOLD+ diet, provide support for including lean beef in a heart-healthy dietary pattern. This trial was registered at clinicaltrials.gov as NCT00937898.","title":"Beef in an Optimal Lean Diet study: effects on lipids, lipoproteins, and apolipoproteins"},{"docid":"MED-1721","text":"Objective To examine the relation between body mass index (kg/m2) and cancer incidence and mortality. Design Prospective cohort study. Participants 1.2 million UK women recruited into the Million Women Study, aged 50-64 during 1996-2001, and followed up, on average, for 5.4 years for cancer incidence and 7.0 years for cancer mortality. Main outcome measures Relative risks of incidence and mortality for all cancers, and for 17 specific types of cancer, according to body mass index, adjusted for age, geographical region, socioeconomic status, age at first birth, parity, smoking status, alcohol intake, physical activity, years since menopause, and use of hormone replacement therapy. Results 45 037 incident cancers and 17 203 deaths from cancer occurred over the follow-up period. Increasing body mass index was associated with an increased incidence of endometrial cancer (trend in relative risk per 10 units=2.89, 95% confidence interval 2.62 to 3.18), adenocarcinoma of the oesophagus (2.38, 1.59 to 3.56), kidney cancer (1.53, 1.27 to 1.84), leukaemia (1.50, 1.23 to 1.83), multiple myeloma (1.31, 1.04 to 1.65), pancreatic cancer (1.24, 1.03 to 1.48), non-Hodgkin's lymphoma (1.17, 1.03 to 1.34), ovarian cancer (1.14, 1.03 to 1.27), all cancers combined (1.12, 1.09 to 1.14), breast cancer in postmenopausal women (1.40, 1.31 to 1.49) and colorectal cancer in premenopausal women (1.61, 1.05 to 2.48). In general, the relation between body mass index and mortality was similar to that for incidence. For colorectal cancer, malignant melanoma, breast cancer, and endometrial cancer, the effect of body mass index on risk differed significantly according to menopausal status. Conclusions Increasing body mass index is associated with a significant increase in the risk of cancer for 10 out of 17 specific types examined. Among postmenopausal women in the UK, 5% of all cancers (about 6000 annually) are attributable to being overweight or obese. For endometrial cancer and adenocarcinoma of the oesophagus, body mass index represents a major modifiable risk factor; about half of all cases in postmenopausal women are attributable to overweight or obesity.","title":"Cancer incidence and mortality in relation to body mass index in the Million Women Study: cohort study"},{"docid":"MED-1724","text":"A considerable amount of evidence is consistent with the proposition that systemic IGF-I activity acts as pacesetter in the aging process. A reduction in IGF-I activity is the common characteristic of rodents whose maximal lifespan has been increased by a wide range of genetic or dietary measures, including caloric restriction. The lifespans of breeds of dogs and strains of rats tend to be inversely proportional to their mature weight and IGF-I levels. The link between IGF-I and aging appears to be evolutionarily conserved; in worms and flies, lifespan is increased by reduction-of-function mutations in signaling intermediates homologous to those which mediate insulin/IGF-I activity in mammals. The fact that an increase in IGF-I activity plays a key role in the induction of sexual maturity, is consistent with a broader role for-IGF-I in aging regulation. If down-regulation of IGF-I activity could indeed slow aging in humans, a range of practical measures for achieving this may be at hand. These include a low-fat, whole-food, vegan diet, exercise training, soluble fiber, insulin sensitizers, appetite suppressants, and agents such as flax lignans, oral estrogen, or tamoxifen that decrease hepatic synthesis of IGF-I. Many of these measures would also be expected to decrease risk for common age-related diseases. Regimens combining several of these approaches might have a sufficient impact on IGF-I activity to achieve a useful retardation of the aging process. However, in light of the fact that IGF-I promotes endothelial production of nitric oxide and may be of especial importance to cerebrovascular health, additional measures for stroke prevention-most notably salt restriction-may be advisable when attempting to down-regulate IGF-I activity as a pro-longevity strategy.","title":"A low-fat, whole-food vegan diet, as well as other strategies that down-regulate IGF-I activity, may slow the human aging process."},{"docid":"MED-1711","text":"Summary Objectives The insulin-like growth factor (IGF) signaling pathway has been implicated in the pathogenesis of numerous tumor types, including non-small cell lung cancer (NSCLC). Figitumumab is a fully human IgG2 monoclonal antibody against IGF-1 receptor (IGF-1R). Methods This phase I, open-label, dose-escalation study (ClinicalTrials.gov: NCT00603538) assessed the safety and tolerability of figitumumab (6, 10 and 20 mg/kg) in combination with carboplatin (area under the curve: 6 mg·min/mL) and paclitaxel (200 mg/m2) in Japanese patients (N = 19) with chemotherapy-naïve, advanced NSCLC. Treatments were administered intravenously on day 1 of a 21-day cycle for four to six cycles. Pharmacokinetics, biomarkers, and antitumor activity were also evaluated. Results Figitumumab in combination with carboplatin and paclitaxel was well tolerated at doses up to 20 mg/kg; no dose-limiting toxicities were observed at this dose level. When given in combination, figitumumab plasma exposure increased in an approximately dose-proportional manner. The approximate 2-fold accumulation following repeated administration supported the 21-day regimen as appropriate for figitumumab administration. Serum total IGF-1 and IGF binding protein-3 concentrations increased following figitumumab dosing, but a clear dose-dependent relationship was not demonstrated. Seven of 18 evaluable patients experienced a partial response. Conclusions Figitumumab 20 mg/kg in combination with carboplatin and paclitaxel was well tolerated in chemotherapy-naïve Japanese patients with NSCLC. Further analysis of biomarker data is necessary for the development of figitumumab therapy.","title":"Figitumumab combined with carboplatin and paclitaxel in treatment-naïve Japanese patients with advanced non-small cell lung cancer"},{"docid":"MED-1258","text":"Reductions in low-density lipoprotein-cholesterol (LDL-C) result from diets containing almonds, or diets that are either low in saturated fat or high in viscous fibers, soy proteins, or plant sterols. We have therefore combined all of these interventions in a single diet (portfolio diet) to determine whether cholesterol reductions could be achieved of similar magnitude to those reported in recent statin trials which reduced cardiovascular events. Twenty-five hyperlipidemic subjects consumed either a portfolio diet (n=13), very low in saturated fat and high in plant sterols (1.2 g/1,000 kcal), soy protein (16.2 g/1,000 kcal), viscous fibers (8.3 g/1,000 kcal), and almonds (16.6 g/1,000 kcal), or a low-saturated fat diet (n=12) based on whole-wheat cereals and low-fat dairy foods. Fasting blood, blood pressure, and body weight were obtained at weeks 0, 2, and 4 of each phase. LDL-C was reduced by 12.1% +/- 2.4% (P<.001) on the low-fat diet and by 35.0% +/- 3.1% (P<.001) on the portfolio diet, which also reduced the ratio of LDL-C to high-density lipoprotein-cholesterol (HDL-C) significantly (30.0% +/- 3.5%; P<.001). The reductions in LDL-C and the LDL:HDL-C ratio were both significantly lower on the portfolio diet than on the control diet (P<.001 and P<.001, respectively). Mean weight loss was similar on test and control diets (1.0 kg and 0.9 kg, respectively). No difference was seen in blood pressure, HDL-C, serum triglycerides, lipoprotein(a) [Lp(a)], or homocysteine concentrations between diets. Combining a number of foods and food components in a single dietary portfolio may lower LDL-C similarly to statins and so increase the potential effectiveness of dietary therapy.","title":"The effect of combining plant sterols, soy protein, viscous fibers, and almonds in treating hypercholesterolemia."},{"docid":"MED-3775","text":"We investigated the beneficial effects of drinking supplementary water during the school day on the cognitive performance and transitory subjective states, such as fatigue or vigor, in 168 children aged between 9 and 11years who were living in a hot climate (South Italy, Sardinia). The classes were randomly divided into an intervention group, which received water supplementation, and a control group. Dehydration was determined by urine sampling and was defined as urine osmolality greater than 800mOsm/kg H(2)O (Katz, Massry, Agomn, & Toor, 1965). The change in the scores from the morning to the afternoon of hydration levels, cognitive performance and transitory subjective states were correlated. In line with a previous observational study that evaluated the hydration status of school children living in a country with a hot climate (Bar-David, Urkin, & Kozminsky, 2005), our results showed that a remarkable proportion of children were in a state of mild, voluntary dehydration at the beginning of the school day (84%). We found a significant negative correlation between dehydration and the auditory number span, which indicates a beneficial effect of drinking supplementary water at school on short-term memory. Moreover, there was a positive correlation between dehydration and performance in the verbal analogy task. The results are discussed in the light of the complexity of the neurobiological mechanisms involved in the relationship between hydration status and cognition. Copyright © 2012 Elsevier Ltd. All rights reserved.","title":"Effects of drinking supplementary water at school on cognitive performance in children."},{"docid":"MED-2445","text":"Allergic disorders encompass skin, food and respiratory allergies. Sensitization to a normally harmless allergen results in the immune system being biased to a predominant T-helper type 2 response. Re-exposure to the same allergen leads to a robust secretion of allergy-related mediators that eventually triggers symptoms. Our understanding of these disorders has enabled the search of therapeutic approaches that can either modulate the sensitization process or impact on allergic mediators, thus helping manage allergic symptoms. Polyphenols are one such class of compounds that are found in foods and plant sources and have been investigated for their anti-allergic effect in different disease models and in human clinical trials. Their anti-inflammatory profile is known to impact on the recruitment of immune cells to the skin and in preventing the development of secondary infections following disruption of the skin barrier. The interaction of polyphenols with proteins can modulate the process of allergic sensitization and their direct effect on allergic effector cells such as mast cells inhibit mediator release, resulting in the alleviation of symptoms. In addition, their endogenous anti-oxidant ability limits the extent of cellular injury from free radicals during the allergic insult. Overall, polyphenols hold promise as anti-allergy agents capable of influencing multiple biological pathways and immune cell functions in the allergic immune response and deserve further investigation. The objective of the current review is to summarize the key findings and progress made in studying polyphenols as anti-allergic ingredients. Special emphasis is placed in this review to highlight key physiological, cellular and signalling pathways implicated in the mechanism of action of different polyphenols in the context of allergic disorders and their manifestations. © 2011 Blackwell Publishing Ltd.","title":"Dietary polyphenols in the prevention and treatment of allergic diseases."},{"docid":"MED-3278","text":"Lung cancer (LC) continues to represent a heavy burden for health care systems worldwide. Epidemiological studies predict that its role will increase in the near future. While patient prognosis is strongly associated with tumour stage and early detection of disease, no screening test exists so far. It has been suggested that electronic sensor devices, commonly referred to as ‘electronic noses’, may be applicable to identify cancer-specific volatile organic compounds in the breath of patients and therefore may represent promising screening technologies. However, three decades of research did not bring forward a clinically applicable device. Here, we propose a new research approach by involving specially trained sniffer dogs into research strategies by making use of their ability to identify LC in the breath sample of patients.","title":"Sniffer dogs as part of a bimodal bionic research approach to develop a lung cancer screening"},{"docid":"MED-3958","text":"Flanders is densely populated with much industry and intensive farming. Sexual maturation of adolescents (aged 14-15 years) was studied in relation to internal exposure to pollutants. Serum levels of pollutants and sex hormones were measured in 1679 participants selected as a random sample of the adolescents residing in the study areas. Data on sexual development were obtained from the medical school examination files. Self-assessment questionnaires provided information on health, use of medication and lifestyle factors. In boys, serum levels of hexachlorobenzene (HCB), p,p'-DDE and polychlorinated biphenyls (sum of marker PCB138, 153 and 180) were significantly and positively associated with pubertal staging (pubic hair and genital development). Higher levels of serum HCB and blood lead were associated with, respectively, a lower and a higher risk of gynecomastia. In girls, significant and negative associations were detected between blood lead and pubic hair development; higher exposure to PCBs was significantly associated with a delay in timing of menarche. Environmental exposures to pollutants at levels actually present in the Flemish population are associated with measurable effects on pubertal development. However, further understanding of toxic mode of action and sensitive windows of exposure is needed to explain the current findings.","title":"Internal exposure to pollutants and sexual maturation in Flemish adolescents."},{"docid":"MED-3451","text":"Oxidative stress is a natural physiological process that describes an imbalance between free radical production and the ability of the antioxidant defence system of the body to neutralize free radicals. Free radicals can be beneficial as they may promote wound healing and contribute to a healthy immune response. However, free radicals can have a detrimental impact when they interfere with the regulation of apoptosis and thus play a role in the promotion of some cancers and conditions such as cardiovascular disease. Antioxidants are molecules that reduce the damage associated with oxidative stress by counteracting free radicals. Regular exercise is a vital component of a healthy lifestyle, although it can increase oxidative stress. As a typical vegetarian diet comprises a wide range of antioxidant-rich foods, it is plausible that the consumption of these foods will result in an enhanced antioxidant system capable of reducing exercise-induced oxidative stress. In addition, a relationship between a vegetarian diet and lower risks of cardiovascular disease and some cancers has been established. This review explores the current available evidence linking exercise, vegetarians, antioxidants, and oxidative stress.","title":"Could a vegetarian diet reduce exercise-induced oxidative stress? A review of the literature."},{"docid":"MED-3954","text":"BACKGROUND: A male epidemic of ischaemic heart disease (IHD) emerges with economic development. It has previously been hypothesised that this epidemic is due to nutritionally driven levels of pubertal sex steroids, which lead to a more atherogenic body shape and lipid profile in boys but not girls, without any sex-specific effects on glucose metabolism. This study tests this hypothesis by examining the association of childhood meat eating with IHD risk in a developing Chinese population. METHODS: Multivariable linear and censored regression was used in a cross-sectional study of 19,418 Chinese older (≥ 50 years) men and women from the Guangzhou Biobank Cohort Study (phases 2 and 3) to assess the adjusted associations of childhood meat eating with waist to hip ratio (WHR), high-density lipoprotein cholesterol and fasting plasma glucose. RESULTS: Adjusted for age, childhood hunger, life-course socioeconomic position and current lifestyle childhood almost daily meat eating compared with less than weekly meat eating was associated with higher WHR (0.007, 95% CI 0.0003 to 0.01) in men but not women. No association with fasting glucose was observed. CONCLUSIONS: Given the potential limitations of this study, especially the crude nature of the exposure and modest findings, the results should be considered as preliminary. However, they do lend support to the hypothesis that the male epidemic of premature IHD and sexual divergence in IHD rates that occur with economic development may be nutritionally driven in childhood. In elucidating the developmental origins of non-communicable chronic diseases, more attention should be focused on the sociohistorical context and the role of puberty.","title":"Does childhood meat eating contribute to sex differences in risk factors for ischaemic heart disease in a developing population?"},{"docid":"MED-2361","text":"The most common clinical manifestation of Lyme disease is the characteristic rash, erythema migrans (EM). In the 1980s EM-like eruptions were reported in Missouri and other southeastern states. The EM-like eruptions, which were of unknown etiology, often followed the bite of the Lone Star tick (Amblyomma americanum) and the rash is called STARI (southern tick-associated rash illness). Although the Lone Star tick is found in the Lyme disease-endemic areas of New England and Mid-Atlantic regions of the United States, STARI has been reported only once from the Northeast and Mid-Atlantic regions. We report a child from Connecticut who visited Long Island, New York, and developed a rash that was thought to be EM. Because the patient failed to respond to antibiotics used to treat Lyme disease, an investigation ensued, and the diagnosis of STARI was established.","title":"Southern Tick-Associated Rash Illness (STARI) in the North: STARI following a tick bite in Long Island, New York."},{"docid":"MED-3776","text":"Little research has examined the effect of water consumption on cognition in children. We examined whether drinking water improves performance from baseline to test in twenty-three 6-7-year-old children. There were significant interactions between time of test and water group (water/no water), with improvements in the water group on thirst and happiness ratings, visual attention and visual search, but not visual memory or visuomotor performance. These results indicate that even under conditions of mild dehydration, not as a result of exercise, intentional water deprivation or heat exposure, children's cognitive performance can be improved by having a drink of water.","title":"Does having a drink help you think? 6-7-Year-old children show improvements in cognitive performance from baseline to test after having a drink of ..."},{"docid":"MED-4897","text":"Consumption of cow's milk and cow's milk protein result in changes of the hormonal axis of insulin, growth hormone and insulin-like growth factor-1(IGF-1) in humans. Milk consumption raises IGF-1 serum levels in the perinatal period, adolescence and adulthood. During puberty with the physiological onset of increased secretion of growth hormone, IGF-1 serum levels increase and are further enhanced by milk consumption. IGF-1 is a potent mitogen; after binding to its receptor in various tissues, it induces cell proliferation and inhibits apoptosis. Keratinocytes and sebocytes, as well as the androgen-synthesizing adrenals and gonads, are stimulated by IGF-1. The epidemic incidence of adolescent acne in Western milk-consuming societies can be explained by the increased insulin- and IGF-1-stimulation of sebaceous glands mediated by milk consumption. Acne can be regarded as a model for chronic Western diseases with pathologically increased IGF-1-stimulation. Many other organs, such as the thymus, bones, all glands, and vascular smooth muscle cells as well as neurons are subject to this abnormally increased hormonal stimulation. The milk-induced change of the IGF-1-axis most likely contributes to the development of fetal macrosomia, induction of atopy, accelerated linear growth, atherosclerosis, carcinogenesis and neurodegenerative diseases. Observations of molecular biology are supported by epidemiologic data and unmask milk consumption as a promoter of chronic diseases of Western societies.","title":"Milk consumption: aggravating factor of acne and promoter of chronic diseases of Western societies."},{"docid":"MED-2826","text":"Background Curcumin extracts of turmeric are proposed to produce health benefits. To date, human intervention studies have focused mainly on people with existing health problems given high doses of poorly absorbed curcumin. The purpose of the current study was to check whether in healthy people, a low dose of a lipidated curcumin extract could alter wellness-related measures. Methods The present study was conducted in healthy middle aged people (40–60 years old) with a low dose of curcumin (80 mg/day) in a lipidated form expected to have good absorption. Subjects were given either curcumin (N = 19) or placebo (N = 19) for 4 wk. Blood and saliva samples were taken before and after the 4 weeks and analyzed for a variety of blood and saliva measures relevant to health promotion. Results Curcumin, but not placebo, produced the following statistically significant changes: lowering of plasma triglyceride values, lowering of salivary amylase levels, raising of salivary radical scavenging capacities, raising of plasma catalase activities, lowering of plasma beta amyloid protein concentrations, lowering of plasma sICAM readings, increased plasma myeloperoxidase without increased c-reactive protein levels, increased plasma nitric oxide, and decreased plasma alanine amino transferase activities. Conclusion Collectively, these results demonstrate that a low dose of a curcumin-lipid preparation can produce a variety of potentially health promoting effects in healthy middle aged people.","title":"Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people"},{"docid":"MED-2655","text":"Background Broad dietary patterns have been linked to asthma but the relative contribution of specific nutrients is unclear. Soy genistein has important anti-inflammatory and other biological effects that might be beneficial in asthma. A positive association was previously reported between soy genistein intake and lung function but not with asthma exacerbations. Aims To conduct a post-hoc analysis of patients with inadequately controlled asthma enrolled in a prospective multicentre clinical trial to replicate this association. Methods A total of 300 study participants were included in the analysis. Dietary soy genistein intake was measured using the Block Soy Foods Screener. The level of soy genistein intake (little or no intake, moderate intake, or high intake) was compared with baseline lung function (pre-bronchodilator forced expiratory volume in 1 second (FEV1)) and asthma control (proportion of participants with an episode of poor asthma control (EPAC) and annualised rates of EPACs over a 6-month follow-up period. Results Participants with little or no genistein intake had a lower baseline FEV1 than those with a moderate or high intake (2.26L vs. 2.53L and 2.47L, respectively; p=0.01). EPACs were more common among those with no genistein intake than in those with a moderate or high intake (54% vs. 35% vs. 40%, respectively; p<0.001). These findings remained significant after adjustment for patient demographics and body mass index. Conclusions In patients with asthma, consumption of a diet with moderate to high amounts of soy genistein is associated with better lung function and better asthma control.","title":"Association of dietary soy genistein intake with lung function and asthma control: a post-hoc analysis of patients enrolled in a prospective multicentre clinical trial"},{"docid":"MED-3458","text":"The single cell gel electrophoresis (SCG) assay (comet assay) is a sensitive technique for detecting the presence of DNA strand-breaks and alkali-labile damage in individual cells. This technique was used to study peripheral blood cells from three volunteers after physical activity. The test subjects had to run on a treadmill and were checked for blood pressure and ECG, lactate concentration and creatine kinase activity. Blood was taken before and several times during and after the run. In a first multiple step test, the volunteers ran as long as possible with increasing speed. In a second test they had to run for 45 min with a fixed individual speed which was defined to ensure an aerobic metabolism. In the first test, the white blood cells of all subjects showed increased DNA migration in the SCG assay. The effect was seen 6 h after the end of the exercise and reached its maximum 24 h later. After 72 h, DNA migration decreased to about control level. The distribution of DNA migration among cells clearly demonstrated that the majority of white blood cells exhibited increased DNA migration and that the effect was not only due to a small fraction of damaged cells. From the same blood samples, blood cultures were set up to study a possible effect on the frequency of sister chromatid exchanges (SCE), another indicator for genotoxic effects. However, there was no significant increase in SCE in any of the cultures. In the second exercise, during aerobic metabolism, the effect on DNA migration was not seen.(ABSTRACT TRUNCATED AT 250 WORDS)","title":"Does physical activity induce DNA damage?"},{"docid":"MED-2586","text":"A systematic review and meta-analysis were carried out to study the effects of low-carbohydrate diet (LCD) on weight loss and cardiovascular risk factors (search performed on PubMed, Cochrane Central Register of Controlled Trials and Scopus databases). A total of 23 reports, corresponding to 17 clinical investigations, were identified as meeting the pre-specified criteria. Meta-analysis carried out on data obtained in 1,141 obese patients, showed the LCD to be associated with significant decreases in body weight (-7.04 kg [95% CI -7.20/-6.88]), body mass index (-2.09 kg m(-2) [95% CI -2.15/-2.04]), abdominal circumference (-5.74 cm [95% CI -6.07/-5.41]), systolic blood pressure (-4.81 mm Hg [95% CI -5.33/-4.29]), diastolic blood pressure (-3.10 mm Hg [95% CI -3.45/-2.74]), plasma triglycerides (-29.71 mg dL(-1) [95% CI -31.99/-27.44]), fasting plasma glucose (-1.05 mg dL(-1) [95% CI -1.67/-0.44]), glycated haemoglobin (-0.21% [95% CI -0.24/-0.18]), plasma insulin (-2.24 micro IU mL(-1) [95% CI -2.65/-1.82]) and plasma C-reactive protein, as well as an increase in high-density lipoprotein cholesterol (1.73 mg dL(-1) [95%CI 1.44/2.01]). Low-density lipoprotein cholesterol and creatinine did not change significantly, whereas limited data exist concerning plasma uric acid. LCD was shown to have favourable effects on body weight and major cardiovascular risk factors; however the effects on long-term health are unknown. © 2012 The Authors. obesity reviews © 2012 International Association for the Study of Obesity.","title":"Systematic review and meta-analysis of clinical trials of the effects of low carbohydrate diets on cardiovascular risk factors."},{"docid":"MED-4058","text":"A facile method was established to measure heterocyclic aromatic amines (HAAs) accumulated in human hair and rodent fur. The samples were digested by base hydrolysis, and the liberated HAAs were isolated by tandem solvent/solid-phase extraction. Quantification was done by liquid chromatography/tandem mass spectrometry, using a triple stage quadrupole mass spectrometer in the selected reaction monitoring mode. In a pilot study of 12 human volunteers, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was detected in hair of six meat-eaters at levels ranging from 290 to 890 pg/g hair. 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-9H-pyrido[2,3-b]indole (AαC) were below the limit of quantification (LOQ) (50 pg/g hair) in hair from meat-eaters and six vegetarians. PhIP was detected in the hair from one vegetarian, and at level just above the LOQ (65 pg/g hair), indicating PhIP exposure occurs primarily through meat consumption. The levels of PhIP in hair samples from two meat-eaters varied by less than 24% over a 6-month interval, signifying that the exposure to PhIP and its accumulation in hair are relatively constant over time. In a controlled feeding study, female C57BL/6 mice were given these HAAs in their drinking water for 1 month, at six daily dose concentrations ranging from 0, 0.080 to 800 µg/kg body weight. PhIP was detected in fur of mice at all doses, whereas AαC and MeIQx were detected in fur at dosages ≥0.8 µg AαC/kg body weight and ≥8 µg MeIQx/kg body weight. There was a strong positive relationship between dosage and each of the HAAs accumulated in fur and their DNA adducts formed in liver and colon (p-values <0.0001); however, the levels of HAA in fur did not correlate to the levels of DNA adducts after adjustment of dose. Thus, hair appears to be a promising long-lived biomarker with by which we can assess the exposure to PhIP, a potential human carcinogen.","title":"Biomonitoring of Carcinogenic Heterocyclic Aromatic Amines in Hair: A Validation Study"},{"docid":"MED-2293","text":"The CODEX Alimentarius definition of dietary fiber includes all nondigestible carbohydrate polymers with a degree of polymerization of 3 or more as dietary fiber with the proviso that they show health benefits. The global definition, if accepted by all authoritative bodies, offers a chance for international harmonization in research, food composition tables, and food labeling. Its nonacceptance highlights problems that may develop when definitions vary by region. The definition requires that the research community agrees upon physiological effects for which there is substantial scientific agreement, e.g., fibers’ effects on laxation and gut health, on attenuating blood lipids and blood glucose and insulin, and in promoting fermentation in the large bowel. The definition also necessitates the delineation of research protocols to prove the benefits of various isolated and synthesized fibers. These should emanate from evidence-based reviews that fairly weigh epidemiological data while considering that added fibers are not reflected in many food composition databases. They then should include well-controlled, randomized, control trials and utilize animal studies to determine mechanisms. Agreement on many study variables such as the type of subject and the type of baseline diet that best fits the question under investigation will also be needed. Finally, the definition establishes that all types of fiber can address the severe fiber consumption gap that exists throughout the world by recognizing that the combination of fiber-rich and -fortified foods increases fiber intake while allowing consumers to stay within allowed energy levels.","title":"Dietary Fiber Future Directions: Integrating New Definitions and Findings to Inform Nutrition Research and Communication"},{"docid":"MED-3959","text":"Context: Earlier age at menarche is associated with rapid infancy weight gain and childhood obesity. The role of hormone levels in mediating these associations is unclear. Objective: The aim of this study was to identify childhood hormone levels at age 8 yr that are associated with early menarche, independent of body size. Design, Settings, and Subjects: A total of 329 girls from a prospective United Kingdom birth cohort study provided blood samples at mean age 8.1 yr (range, 8.0–8.5) for hormone measurements and were followed longitudinally to establish age at menarche. Main Outcome Measures: Fasting plasma levels of IGF-I, androstenedione, dehydroepiandrosterone sulfate (DHEAS), leptin, insulin, IGF binding protein-1, and SHBG were measured. Age at menarche was reported by questionnaire and categorized as before 12.0, 12.0–13.0, or later than 13 yr. Results: Earlier menarche was associated with greater body weight, height, and body mass index at age 8 yr (all P-trend <0.001). Before adjustment for body size, earlier menarche was associated with higher levels of IGF-I, androstenedione, DHEAS, leptin, and fasting insulin, and with lower levels of IGF binding protein-1 and SHBG at age 8 yr (all P < 0.01). After adjustment for body mass index and height at age 8 yr, only IGF-I (P = 0.004), androstenedione (P = 0.01), and DHEAS (P = 0.01) remained associated with earlier menarche. Conclusions: Associations between higher levels of IGF-I and adrenal androgens at age 8 yr with earlier menarche, independent of body size, support functional roles of these hormones in regulating puberty timing in girls. Higher levels of these hormones reported in children who exhibited rapid weight gain during infancy may indicate their role in developmental pathways leading to earlier sexual maturation.","title":"Higher Levels of IGF-I and Adrenal Androgens at Age 8 Years Are Associated with Earlier Age at Menarche in Girls"},{"docid":"MED-2273","text":"Objective To examine and quantify the relation between purine intake and the risk of recurrent gout attacks among gout patients. Methods The authors conducted a case-crossover study to examine associations of a set of putative risk factors with recurrent gout attacks. Individuals with gout were prospectively recruited and followed online for 1 year. Participants were asked about the following information when experiencing a gout attack: the onset date of the gout attack, clinical symptoms and signs, medications (including antigout medications), and presence of potential risk factors (including daily intake of various purine-containing food items) during the 2-day period prior to the gout attack. The same exposure information was also assessed over 2-day control periods. Results This study included 633 participants with gout. Compared with the lowest quintile of total purine intake over a 2-day period, OR of recurrent gout attacks were 1.17, 1.38, 2.21 and 4.76, respectively, with each increasing quintile (p for trend <0.001). The corresponding OR were 1.42, 1.34, 1.77 and 2.41 for increasing quintiles of purine intake from animal sources (p for trend <0.001), and 1.12, 0.99, 1.32 and 1.39 from plant sources (p=0.04), respectively. The effect of purine intake persisted across subgroups by sex, use of alcohol, diuretics, allopurinol, NSAIDs and colchicine. Conclusions The study findings suggest that acute purine intake increases the risk of recurrent gout attacks by almost fivefold among gout patients. Avoiding or reducing amount of purine-rich foods intake, especially of animal origin, may help reduce the risk of gout attacks.","title":"Purine-rich foods intake and recurrent gout attacks"},{"docid":"MED-3781","text":"In this study, a panel of normal human prostate cells (HPCs) and tumor cells derived from metastases were studied by (1)H NMR spectroscopy to determine whether the malignant transformation of HPCs results in the elevation of choline compounds. Although an elevated choline signal has been observed previously in clinical studies, the contribution of the different Cho compounds to this elevation, as well as their quantification, has not been established until now. Here we have shown that HPCs derived from metastases exhibit significantly higher phosphocholine as well as glycerophosphocholine levels compared with normal prostate epithelial and stromal cells. Thus the elevation of the choline peak observed clinically in prostate cancer is attributable to an alteration of phospholipid metabolism and not simply to increased cell density, doubling time, or other nonspecific effects. Androgen deprivation of the androgen receptor-positive cell lines resulted in a significant increase of choline compounds after chronic androgen deprivation of the LNCaP cell line and in a decrease of choline compounds after a more acute androgen deprivation of the LAPC-4 cell line. These data strongly support the use of proton magnetic resonance spectroscopic imaging to detect the presence of prostate cancer for diagnosis, to detect response subsequent to androgen ablation therapy, and to detect recurrence.","title":"Detection of increased choline compounds with proton nuclear magnetic resonance spectroscopy subsequent to malignant transformation of human prosta..."},{"docid":"MED-2363","text":"We have previously shown that an antibody pool present in normal human serum binds cytokine receptors in vitro and may therefore interfere with assays that capture cytokines using their receptors. Here we show that this antibody pool is the same as the natural antibody termed anti-gal, that binds to the alpha-galactosyl carbohydrate epitope (alpha-gal) and which is the predominant obstacle to xenotransplantation. We report that there are high levels of IgD anti alpha-gal in most volunteers, in addition to the IgG2, IgA and IgM immunoglobulin isotypes against alpha-gal previously described. To determine if anti-gal may interfere with assays that depend on capture of cytokine with its receptor, we measured levels of several anti-carbohydrate antibodies in a cohort of patients with advanced atherosclerosis that had previously been used to measure levels of active TGF-beta using such an assay. For many isotype / carbohydrate combinations, there is a large and significant difference between the levels of anti-carbohydrate antibodies in patients with atherosclerosis and controls, after adjustment for age, sex and blood group. These results are similar to the previous data obtained for active TGF-beta, and therefore we cannot discount the possibility that anti-gal contributed to the previous data. Following further adjustment for several risk factors associated with cardiovascular disease, several anti-carbohydrate antibodies were still significantly different between patients and controls. Therefore, anti-carbohydrate antibodies may represent a new class of risk factors that may be associated with presence of advanced atherosclerosis, although larger studies will be required to confirm this hypothesis.","title":"A pattern of anti-carbohydrate antibody responses present in patients with advanced atherosclerosis."},{"docid":"MED-1609","text":"To examine extra-alimentary effects of high-carbohydrate, high-fiber (HCF) diets, insulin-mediated glucose disposal employing the euglycemic clamp and hepatic glucose output (HGO) employing [6,6-2H2]glucose were measured in 12 healthy young and old individuals before and after 21-28 d of an HCF diet. Diet lowered fasting concentrations of glucose from 5.3 +/- 0.2 to 5.1 +/- 0.1 mmol/L (p less than 0.01) and insulin from 66.0 +/- 7.9 to 49.5 +/- 5.7 pmol/L (p less than 0.01). Fasting serum cholesterol decreased from 5.17 +/- 0.18 to 3.80 +/- 0.20 mmol/L (p less than 0.01) in young individuals and from 6.15 +/- 0.52 to 4.99 +/- 0.49 mmol/L (p less than 0.01) in elderly individuals. Fasting serum triglyceride concentrations, basal HGO, and insulin suppression of HGO were unchanged by the diet. Glucose disposal rates increased from 18.87 +/- 1.66 before 23.87 +/- 2.78 mumol.kg-1.min-1 after the diet (p less than 0.02). Therefore, HCF diets may improve carbohydrate economy by enhanced peripheral sensitivity to insulin.","title":"High-carbohydrate, high-fiber diets increase peripheral insulin sensitivity in healthy young and old adults."},{"docid":"MED-3927","text":"Objective: Epidemiologic studies consistently link caffeine, a nonselective adenosine antagonist, to lower risk of Parkinson disease (PD). However, the symptomatic effects of caffeine in PD have not been adequately evaluated. Methods: We conducted a 6-week randomized controlled trial of caffeine in PD to assess effects upon daytime somnolence, motor severity, and other nonmotor features. Patients with PD with daytime somnolence (Epworth >10) were given caffeine 100 mg twice daily ×3 weeks, then 200 mg twice daily ×3 weeks, or matching placebo. The primary outcome was the Epworth Sleepiness Scale score. Secondary outcomes included motor severity, sleep markers, fatigue, depression, and quality of life. Effects of caffeine were analyzed with Bayesian hierarchical models, adjusting for study site, baseline scores, age, and sex. Results: Of 61 patients, 31 were randomized to placebo and 30 to caffeine. On the primary intention-to-treat analysis, caffeine resulted in a nonsignificant reduction in Epworth Sleepiness Scale score (−1.71 points; 95% confidence interval [CI] −3.57, 0.13). However, somnolence improved on the Clinical Global Impression of Change (+0.64; 0.16, 1.13, intention-to-treat), with significant reduction in Epworth Sleepiness Scale score on per-protocol analysis (−1.97; −3.87, −0.05). Caffeine reduced the total Unified Parkinson's Disease Rating Scale score (−4.69 points; −7.7, −1.6) and the objective motor component (−3.15 points; −5.50, −0.83). Other than modest improvement in global health measures, there were no changes in quality of life, depression, or sleep quality. Adverse events were comparable in caffeine and placebo groups. Conclusions: Caffeine provided only equivocal borderline improvement in excessive somnolence in PD, but improved objective motor measures. These potential motor benefits suggest that a larger long-term trial of caffeine is warranted. Classification of evidence: This study provides Class I evidence that caffeine, up to 200 mg BID for 6 weeks, had no significant benefit on excessive daytime sleepiness in patients with PD.","title":"Caffeine for treatment of Parkinson disease"},{"docid":"MED-4308","text":"We examined the occurrence and coincidence of depressed mood and excessive carbohydrate intake in 19 patients who claimed to suffer from severe premenstrual syndrome and in nine control subjects, all as inpatients, during the early follicular and late luteal phases of their menstrual cycles. Mood was assessed with the Hamilton Depression Scale and an addendum that evaluated fatigue, sociability, appetite, and carbohydrate craving. Calorie and nutrient intakes were measured directly. The subjects with premenstrual syndrome significantly increased calorie intake during the late luteal phase (from 1892 +/- 104 to 2395 +/- 93 kcal, mean +/- SEM); carbohydrate intake increased by 24% from meals and by 43% from snacks. Protein intake failed to change, whereas intake of fat, a fixed constituent of all of the test foods, rose in proportion to calorie intake. The Hamilton Depression Scale and addendum scores rose from 2.0 +/- 0.5 to 21.2 +/- 0.8 (Hamilton Scale) and from 0.5 +/- 0.5 to 10.2 +/- 0.6 (addendum) among subjects with premenstrual syndrome during the luteal phase but failed to change among the controls (2.1 +/- 0.8 to 2.4 +/- 0.8, and 0.4 +/- 0.3 to 0.6 +/- 0.3). Consumption of a carbohydrate-rich, protein-poor evening test meal during the late luteal phase of the menstrual cycle improved depression, tension, anger, confusion, sadness, fatigue, alertness, and calmness scores (p less than 0.01) among patients with premenstrual syndrome. No effect of the meal was observed during the follicular phase or among the control subjects during either phase. Because synthesis of brain serotonin, which is known to be involved in mood and appetite, increases after carbohydrate intake, premenstrual syndrome subjects may overconsume carbohydrates in an attempt to improve their dysphoric mood state.","title":"Effect of nutrient intake on premenstrual depression."},{"docid":"MED-2510","text":"Dietary restriction (DR) extends the lifespan of a wide range of species, although the universality of this effect has never been quantitatively examined. Here, we report the first comprehensive comparative meta-analysis of DR across studies and species. Overall, DR significantly increased lifespan, but this effect is modulated by several factors. In general, DR has less effect in extending lifespan in males and also in non-model organisms. Surprisingly, the proportion of protein intake was more important for life extension via DR than the degree of caloric restriction. Furthermore, we show that reduction in both age-dependent and age-independent mortality rates drives life extension by DR among the well-studied laboratory model species (yeast, nematode worms, fruit flies and rodents). Our results suggest that convergent adaptation to laboratory conditions better explains the observed DR-longevity relationship than evolutionary conservation although alternative explanations are possible. © 2012 The Authors. Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.","title":"Comparative and meta-analytic insights into life extension via dietary restriction."},{"docid":"MED-3771","text":"OBJECTIVE: Hyperosmotic stress on cells limits many aspects of cell function, metabolism and health. International data suggest that schoolchildren may be at risk of hyperosmotic stress on cells because of suboptimal water intake. The present study explored the cell hydration status of two samples of children in the USA. DESIGN: Cross-sectional study describing the urine osmolality (an index of hyperosmotic cell shrinkage) and water intake of convenience samples from Los Angeles (LA) and New York City (NYC). SETTING: Each participant collected a urine sample at an outpatient clinic on the way to school on a weekday morning in spring 2009. Each was instructed to wake, eat, drink and do as usual before school, and complete a dietary record form describing the type and amounts of all foods and beverages consumed after waking, before giving the sample. SUBJECTS: The children (9-11 years) in LA (n 337) and NYC (n 211) considered themselves healthy enough to go to school on the day they gave the urine sample. RESULTS: Elevated urine osmolality (>800 mmol/kg) was observed in 63 % and 66 % of participants in LA and NYC, respectively. In multivariable-adjusted logistic regression models, elevated urine osmolality was associated with not reporting intake of drinking water in the morning (LA: OR = 2·1, 95 % CI 1·2, 3·5; NYC: OR = 1·8, 95 % CI 1·0, 3·5). Although over 90 % of both samples had breakfast before giving the urine sample, 75 % did not drink water. CONCLUSIONS: Research is warranted to confirm these results and pursue their potential health implications.","title":"What is the cell hydration status of healthy children in the USA? Preliminary data on urine osmolality and water intake."},{"docid":"MED-4306","text":"When plasma tryptophan is elevated by the injection of tryptophan or insulin, or by the consumption of carbohydrates, brain tryptophan and serotonin also rise; however, when even larger elevations of plasma tryptophan are produced by the ingestion of protein-containing diets, brain tryptophan and serotonin do not change. The main determinant of brain tryptophan and serotonin concentrations does not appear to be plasma tryptophan alone, but the ratio of this amino acid to other plasma neutral amino acids (that is, tyrosine, phenylalanine, leucine, isoleucine, and valine) that compete with it for uptake into the brain.","title":"Brain serotonin content: physiological regulation by plasma neutral amino acids."},{"docid":"MED-3930","text":"Studies that have addressed the association between the intake of coffee or caffeine and Parkinson's disease (PD) were conducted mainly in Western countries. Little is known about this relationship in an Asian population. Therefore, we performed an assessment of the association of the intake of coffee, other caffeine-containing beverages, and caffeine with the risk of PD in Japan. The study involved 249 PD cases and 368 control subjects. Information on dietary factors was obtained through a self-administered diet history questionnaire. Adjustment was made for sex, age, region of residence, educational level, pack-years of smoking, body mass index, the dietary glycemic index, and intake of cholesterol, vitamin E, β-carotene, vitamin B(6,) alcohol, and iron. Intake of coffee, black tea, and Japanese and Chinese teas was significantly inversely associated with the risk of PD: the adjusted odds ratios in comparison of the highest with the lowest quartile were 0.52, 0.58, and 0.59, respectively (95% confidence intervals = 0.30-0.90, 0.35-0.97, and 0.35-0.995, respectively). A clear inverse dose-response relationship between total caffeine intake and PD risk was observed. We confirmed that the intake of coffee and caffeine reduced the risk of PD. Furthermore, this is the first study to show a significant inverse relationship between the intake of Japanese and Chinese teas and the risk of PD. Copyright © 2011 Elsevier Ltd. All rights reserved.","title":"Intake of Japanese and Chinese teas reduces risk of Parkinson's disease."},{"docid":"MED-4953","text":"Objective To evaluate whether intake of protein from animal and vegetable origin is associated with ovulatory infertility. Study Design 18,555 married women without a history of infertility were followed as they attempted a pregnancy or became pregnant during an eight year period. Dietary assessments were related to the incidence of ovulatory infertility. Results During follow-up, 438 women reported ovulatory infertility. The multivariate-adjusted relative risk [RR] (95% CI; P, trend) of ovulatory infertility comparing the highest to the lowest quintile of animal protein intake was 1.39 (1.01 – 1.90; 0.03). The corresponding RR (95% CI; P, trend) for vegetable protein intake was 0.78 (0.54 – 1.12; 0.07). Further, consuming 5% of total energy intake as vegetable protein rather than as animal protein was associated with a more than 50% lower risk of ovulatory infertility (P = 0.007). Conclusions Replacing animal sources of protein with vegetable sources of protein may reduce ovulatory infertility risk.","title":"Protein intake and ovulatory infertility"},{"docid":"MED-1611","text":"A growing body of evidence from observational studies and meta-analyses of the data suggest that diabetes mellitus is associated with an increased risk of cancer. Meta-analyses have shown that diabetes increases the risks of total cancer, and of site-specific cancers of the breast, endometrium, bladder, liver, colorectum and pancreas, and that it decreases the risk of prostate cancer. Insulin resistance and secondary hyperinsulinemia is the most frequently proposed hypothesis, and hyperglycemia itself might promote carcinogenesis. In addition to several facets of lifestyle including obesity, smoking and lack of exercise, treatment for diabetes might affect the risk of cancer. For instance, metformin, an insulin sensitizer, reportedly has a potential anticancer effect. In light of the exploding global epidemic of diabetes, even a modest increase in the cancer risk will translate into a substantial socioeconomic burden. The current insights underscore the need for clinical attention and better-designed studies of the complex interactions between diabetes and cancer.","title":"Latest insights into the risk of cancer in diabetes"},{"docid":"MED-3449","text":"Watercress (Cruciferae), an integral part of Mediterranean diets, is a nutritive food which is used in the treatment of several diseases. Oxidative DNA damage seems to play a crucial role in chronic, aging-related diseases and it is considered an important and probably carcinogenic factor. The aim of this work was to determine the impact of watercress extract on cell viability and its potential antigenotoxic properties against induced oxidative damage, using a comet assay and peripheral blood cells as an in vitro model. An aqueous extract of the leaves was prepared using a juice processor, centrifuged, filtered and preserved at -20 °C. Two concentrations of the aqueous extract (13.2 and 26.4 mg/mL) were assayed. No differences were found in cell viability between the control and treated groups at any time. Significant antigenotoxic effects were observed for both concentrations, expressed as the damage index (p = 0.005 at 30 min; p < 0.001 at 60 and 90 min), the percentage reductions in damage being similar between them (67.1-75.2% respectively). These results suggest that the consumption watercress in the diet is a powerful tool for improving health and the quality of life. Copyright © 2011 John Wiley & Sons, Ltd.","title":"Antigenotoxic activity of watercress extract in an in vitro mammalian system using comet assay."},{"docid":"MED-1582","text":"Background & Aims Increased intake of dietary fiber has been proposed to reduce risk of inflammatory bowel diseases (Crohn’s disease [CD], ulcerative colitis [UC]). However, few prospective studies have examined associations between long-term intake of dietary fiber and risk of incident CD or UC. Methods We collected and analyzed data from 170,776 women, followed over 26 y, who participated in the Nurses’ Health Study, followed for 3,317,425 person-y. Dietary information was prospectively ascertained via administration of a validated semi-quantitative food frequency questionnaire every 4 y. Self-reported CD and UC were confirmed through review of medical records. Cox proportional hazards models, adjusting for potential confounders, were used to calculate hazard ratios (HRs). Results We confirmed 269 incident cases of CD (incidence 8/100,000 person-y) and 338 cases of UC (incidence 10/100,000 person-y). Compared to the lowest quintile of energy-adjusted cumulative average intake of dietary fiber, intake of the highest quintile (median of 24.3 g/day) was associated with a 40% reduction in risk of CD (multivariate HR for CD, 0.59; 95% confidence interval [CI], 0.39–0.90). This apparent reduction appeared to be greatest for fiber derived from fruits; fiber from cereals, whole grains, or legumes did not modify risk. In contrast, neither total intake of dietary fiber (multivariate HR, 0.82; 95% CI 0.58–1.17) nor intake of fiber from specific sources appeared to be significantly associated with risk of UC. Conclusion Based on data from the Nurses’ Health Study, long-term intake of dietary fiber, particularly from fruit, is associated with lower risk of CD but not UC. Further studies are needed to determine the mechanisms that mediate this association.","title":"A Prospective Study of Long-term Intake of Dietary Fiber and Risk of Crohn’s Disease and Ulcerative Colitis"},{"docid":"MED-2662","text":"A human breast cancer cell line (MCF-7) was used to develop an in vitro screening assay for the detection of xenoestrogenic environmental pollutants. MCF-7 cells were cultured in DMEM containing 5% fetal bovine serum (FBS). An estrogenic response was defined as an increase in the frequency of proliferating MCF-7 cells, and was measured using a thymidine analog, bromodeoxyuridine, and flow cytometry. Di-2-ethylhexyl phthalate (DEHP) and 4-n-nonylphenol (4-n-NP) were used as model chemicals. The proliferation rate of S-phase cells after 24 h of exposure to various concentrations of 17beta-estradiol and to model compounds was compared with a positive and a negative control, containing 1 nM 17beta-estradiol and 0.1% ethanol, respectively. DEHP and 4-n-NP increased the frequency of proliferating MCF-7 cells in a dose-dependent manner. The lowest concentration that significantly increased the proliferation of MCF-7 cells was 10 microM for DEHP and 1 microM for 4-n-NP. The results showed that the assay is accurate and quick to perform. It may prove a valuable tool for screening potential estrogen-mimicking environmental pollutants.","title":"Effects of xenoestrogenic environmental pollutants on the proliferation of a human breast cancer cell line (MCF-7)."},{"docid":"MED-5182","text":"BACKGROUND: Reports of relationships between dietary fibre intake and breast cancer have been inconsistent. Previous cohort studies have been limited by a narrow range of intakes. METHODS: Women who developed invasive breast cancer, 350 post-menopausally and 257 pre-menopausally, during 240,959 person-years of follow-up in the UK Women's Cohort Study (UKWCS) were studied. This cohort has 35,792 subjects with a wide range of exposure to dietary fibre with intakes of total fibre in the lowest quintile of <20 g/day up to >30 g/day in the top quintile. Fibre and breast cancer relationships were explored using Cox regression modelling adjusted for measurement error. Effects of fibre, adjusting for confounders were examined for pre- and post-menopausal women separately. RESULTS: In pre-menopausal, but not post-menopausal women a statistically significant inverse relationship was found between total fibre intake and risk of breast cancer (P for trend = 0.01). The top quintile of fibre intake was associated with a hazard ratio of 0.48 [95% confidence interval (CI) 0.24-0.96] compared with the lowest quintile. Pre-menopausally, fibre from cereals was inversely associated with risk of breast cancer (P for trend = 0.05) and fibre from fruit had a borderline inverse relationship (P for trend = 0.09). A further model including dietary folate strengthened the significance of the inverse relationship between total fibre and pre-menopausal breast cancer. CONCLUSIONS: These findings suggest that in pre-menopausal women, total fibre is protective against breast cancer; in particular, fibre from cereals and possibly fruit.","title":"Dietary fibre and risk of breast cancer in the UK Women's Cohort Study."},{"docid":"MED-1187","text":"Background and aims: The causes of relapses of ulcerative colitis (UC) are unknown. Dietary factors have been implicated in the pathogenesis of UC. The aim of this study was to determine which dietary factors are associated with an increased risk of relapse of UC. Methods: A prospective cohort study was performed with UC patients in remission, recruited from two district general hospitals, who were followed for one year to determine the effect of habitual diet on relapse. Relapse was defined using a validated disease activity index. Nutrient intake was assessed using a food frequency questionnaire and categorised into tertiles. Adjusted odds ratios for relapse were determined using multivariate logistic regression, controlling for non-dietary factors. Results: A total of 191 patients were recruited and 96% completed the study. Fifty two per cent of patients relapsed. Consumption of meat (odds ratio (OR) 3.2 (95% confidence intervals (CI) 1.3–7.8)), particularly red and processed meat (OR 5.19 (95% CI 2.1–12.9)), protein (OR 3.00 (95% CI 1.25–7.19)), and alcohol (OR 2.71 (95% CI 1.1–6.67)) in the top tertile of intake increased the likelihood of relapse compared with the bottom tertile of intake. High sulphur (OR 2.76 (95% CI 1.19–6.4)) or sulphate (OR 2.6 (95% CI 1.08–6.3)) intakes were also associated with relapse and may offer an explanation for the observed increased likelihood of relapse. Conclusions: Potentially modifiable dietary factors, such as a high meat or alcoholic beverage intake, have been identified that are associated with an increased likelihood of relapse for UC patients. Further studies are needed to determine if it is the sulphur compounds within these foods that mediates the likelihood of relapse and if reducing their intake would reduce relapse frequency.","title":"Influence of dietary factors on the clinical course of ulcerative colitis: a prospective cohort study"},{"docid":"MED-3226","text":"Context and Objective: Dietary intake of animal proteins is associated with an increase in urinary calcium and nephrolithiasis risk. We tested the hypothesis that the acid load imposed by dietary proteins causes this hypercalciuria. Design and Setting: In a short-term crossover metabolic study, an alkali salt was provided with a high-protein diet (HPD) to neutralize the acid load imparted by dietary proteins. Participants and Interventions: Eleven healthy volunteers were evaluated at the end of each of four phases while consuming metabolic diets with fixed calcium and sodium content. Phases 1 and 3 consisted of a control diet (CD). Phases 2 and 4 consisted of a eucaloric HPD (60 g/d animal proteins added to CD). Along with HPD in phases 2 and 4, subjects ingested 30 mEq twice daily of either potassium citrate (KCitrate, alkaline salt) or potassium chloride (KCl, control neutral salt). Results: KCitrate completely neutralized the acid load imparted by HPD (based on changes in urine pH and net acid excretion) and increased urinary citrate. Urinary calcium increased during both HPD phases compared with CD but was not significantly different between the HPD + KCl and HPD + KCitrate phases (182 ± 85 vs. 170 ± 85 mg/d; P = 0.28). Increased urinary saturation with respect to calcium oxalate and uric acid with HPD was abrogated by KCitrate. Conclusions: This study suggests that, at least in the short-term, mechanism(s) other than acid load account for hypercalciuria induced by HPD. The beneficial effect of KCitrate on nephrolithiasis risk with HPD is through correction of declines in urine pH and citrate.","title":"Hypercalciuria Associated with High Dietary Protein Intake Is Not Due to Acid Load"},{"docid":"MED-2506","text":"Long-term caloric restriction (CR) is a robust means of reducing age-related diseases and extending life span in multiple species, but the effects in humans are unknown. The low caloric intake, long life expectancy, and the high prevalence of centenarians in Okinawa have been used as an argument to support the CR hypothesis in humans. However, no long-term, epidemiologic analysis has been conducted on traditional dietary patterns, energy balance, and potential CR phenotypes for the specific cohort of Okinawans who are purported to have had a calorically restricted diet. Nor has this cohort's subsequent mortality experience been rigorously studied. Therefore, we investigated six decades of archived population data on the elderly cohort of Okinawans (aged 65-plus) for evidence of CR. Analyses included traditional diet composition, energy intake, energy expenditure, anthropometry, plasma DHEA, mortality from age-related diseases, and current survival patterns. Findings include low caloric intake and negative energy balance at younger ages, little weight gain with age, life-long low BMI, relatively high plasma DHEA levels at older ages, low risk for mortality from age-related diseases, and survival patterns consistent with extended mean and maximum life span. This study lends epidemiologic support for phenotypic benefits of CR in humans and is consistent with the well-known literature on animals with regard to CR phenotypes and healthy aging.","title":"Caloric restriction, the traditional Okinawan diet, and healthy aging: the diet of the world's longest-lived people and its potential impact on mor..."},{"docid":"MED-1254","text":"OBJECTIVE: To investigate the effect of replacing lean meat with a soy product, tofu, on coronary heart disease risk factors including serum lipoproteins, lipoprotein (a), factor VII, fibrinogen and in vitro susceptibility of LDL to oxidation. DESIGN: A randomized cross over dietary intervention study. SETTING: Free-living individuals studied at Deakin University. SUBJECTS: Forty-five free-living healthy males aged 35 to 62 years completed the dietary intervention. Three subjects were non-compliant and excluded prior to analysis. INTERVENTIONS: A diet containing 150 grams of lean meat per day was compared to a diet containing 290 grams of tofu per day in an isocaloric and isoprotein substitution. Each dietary period was one month duration. RESULTS: Analysis of the seven-day diet record showed that diets were similar in energy, protein, carbohydrate, total fat, saturated and unsaturated fat, polyunsaturated to saturated fat ratio, alcohol and fiber. Total cholesterol and triglycerides were significantly lower, and in vitro LDL oxidation lag phase was significantly longer on the tofu diet compared to the meat diet. The hemostatic factors, factor VII and fibrinogen, and lipoprotein(a) were not significantly affected by the tofu diet. CONCLUSIONS: The increase in LDL oxidation lag phase would be expected to be associated with a decrease in coronary heart disease risk.","title":"Effect of meat replacement by tofu on CHD risk factors including copper induced LDL oxidation."},{"docid":"MED-2272","text":"To assess the physiologic effects of cherry consumption, we measured plasma urate, antioxidant and inflammatory markers in 10 healthy women who consumed Bing sweet cherries. The women, age 22-40 y, consumed two servings (280 g) of cherries after an overnight fast. Blood and urine samples were taken before the cherry dose, and at 1.5, 3 and 5 h postdose. Plasma urate decreased 5 h postdose, mean +/- SEM = 183 +/- 15 micro mol/L compared with predose baseline of 214 +/- 13 micro mol/L (P < 0.05). Urinary urate increased postdose, with peak excretion of 350 +/- 33 micro mol/mmol creatinine 3 h postdose compared with 202 +/- 13 at baseline (P < 0.01). Plasma C-reactive protein (CRP) and nitric oxide (NO) concentrations had decreased marginally 3 h postdose (P < 0.1), whereas plasma albumin and tumor necrosis factor-alpha were unchanged. The vitamin C content of the cherries was solely as dehydroascorbic acid, but postdose increases in plasma ascorbic acid indicated that dehydroascorbic acid in fruits is bioavailable as vitamin C. The decrease in plasma urate after cherry consumption supports the reputed anti-gout efficacy of cherries. The trend toward decreased inflammatory indices (CRP and NO) adds to the in vitro evidence that compounds in cherries may inhibit inflammatory pathways.","title":"Consumption of cherries lowers plasma urate in healthy women."},{"docid":"MED-2504","text":"It is well established that the target of rapamycin (TOR) protein kinase has pivotal roles in controlling cell functions (including protein synthesis, cell growth and cell proliferation) and is implicated in numerous human diseases. Mammalian TOR complex 1 (mTORC1) signalling is activated by hormones and growth factors, and is also stimulated by intracellular amino acids. Recent research has provided important new insight into the poorly understood mechanism by which amino acids activate mTORC1 signalling, showing that the protein kinase MAP4K3 and Rag GTPases have important roles in this. mTORC1 is known to control the G1/S transition of the cell cycle: new data show that (m)TORC1 also controls G2/M progression in yeast and mammals, albeit in contrasting ways.","title":"Nutrient control of TORC1, a cell-cycle regulator."},{"docid":"MED-4886","text":"OBJECTIVES: Previous research has demonstrated that patients with prostate cancer participating in the Prostate Cancer Lifestyle Trial had a reduction in prostate-specific antigen (PSA) levels, inhibition of LNCaP cell growth, and fewer prostate cancer-related clinical events at the end of 1 year compared with controls. The aim of this study was to examine the clinical events in this trial during a 2-year period. METHODS: The Prostate Cancer Lifestyle Trial was a 1-year randomized controlled clinical trial of 93 patients with early-stage prostate cancer (Gleason score <7, PSA 4-10 ng/mL) undergoing active surveillance. The patients in the experimental arm were encouraged to adopt a low-fat, plant-based diet, to exercise and practice stress management, and to attend group support sessions. The control patients received the usual care. RESULTS: By 2 years of follow-up, 13 of 49 (27%) control patients and 2 of 43 (5%) experimental patients had undergone conventional prostate cancer treatment (radical prostatectomy, radiotherapy, or androgen deprivation, P < .05). No differences were found between the groups in other clinical events (eg, cardiac), and no deaths occurred. Three of the treated control patients but none of the treated experimental patients had a PSA level of >or=10 ng/mL, and 1 treated control patient but no treated experimental patients had a PSA velocity of >2 ng/mL/y before treatment. No significant differences were found between the untreated experimental and untreated control patients in PSA change or velocity at the end of 2 years. CONCLUSIONS: Patients with early-stage prostate cancer choosing active surveillance might be able to avoid or delay conventional treatment for at least 2 years by making changes in their diet and lifestyle.","title":"Clinical events in prostate cancer lifestyle trial: results from two years of follow-up."},{"docid":"MED-3271","text":"Most metastatic tumors, such as those originating in the prostate, lung, and gastrointestinal tract, respond poorly to conventional chemotherapy. Novel treatment strategies for advanced cancer are therefore desperately needed. Dietary restriction of the essential amino acid methionine offers promise as such a strategy, either alone or in combination with chemotherapy or other treatments. Numerous in vitro and animal studies demonstrate the effectiveness of dietary methionine restriction in inhibiting growth and eventually causing death of cancer cells. In contrast, normal host tissues are relatively resistant to methionine restriction. These preclinical observations led to a phase I clinical trial of dietary methionine restriction for adults with advanced cancer. Preliminary findings from this trial indicate that dietary methionine restriction is safe and feasible for the treatment of patients with advanced cancer. In addition, the trial has yielded some preliminary evidence of antitumor activity. One patient with hormone-independent prostate cancer experienced a 25% reduction in serum prostate-specific antigen (PSA) after 12 weeks on the diet, and a second patient with renal cell cancer experienced an objective radiographic response. The possibility that methionine restriction may act synergistically with other cancer treatments such as chemotherapy is being explored. Findings to date support further investigation of dietary methionine restriction as a novel treatment strategy for advanced cancer.","title":"Can dietary methionine restriction increase the effectiveness of chemotherapy in treatment of advanced cancer?"},{"docid":"MED-3127","text":"AIM: Isoflavones in soy foods are part of a larger class of flayonoid compounds that have have been demonstrated to be potent dietary anti-cancer agents, and the effect of soy intake on the survival of ovarian cancer is conflicting. Therefore, we aimed to explore the whether soy intake is related to the risk of death of breast cancer. METHODS: A prospective study was conducted. A total of 256 patients included in this study had breast cancer and were recruited between January 2004 and January 2006. All of them were followed up from since January 2011. A univariate Cox's regression analysis was used to assess the association between soy intake and survival. RESULTS: The education level, menopausal status, ER/PR status and TNM stage were significant difference in the survival of breast cancer. The highest soy isoflavone was associated with a decreased death risk of breast cancer (OR=0.25, 95% CI=0.09-0.54). Moreover, the higher consumption of soy protein also presented a trend decreased breast cancer risk, and the highest consumption significantly reduced the cancer risk compared with the lowest consumption (OR=0.38, 95% CI=0.17-0.86). CONCLUSION: The present study suggests soy intake is associated with a significant reduced death risk of breast cancer in Chinese population. Further large sample studies are warranted to confirm the inverse association of soy consumption and breast cancer survival by menopausal status.","title":"Study on soy isoflavone consumption and risk of breast cancer and survival."},{"docid":"MED-3230","text":"OBJECTIVE: Diet affects urine pH and acid-base balance. Both excess acid/alkaline ash (EAA) and estimated net acid excretion (NAE) calculations have been used to estimate the effects of diet on urine pH. This study's goal was to determine if free-living vegans, lacto-ovo vegetarians, and omnivores have increasingly acidic urine, and to assess the ability of EAA and estimated NAE calculations to predict urine pH. DESIGN: This study used a cross-sectional design. SETTING AND PARTICIPANTS: This study assessed urine samples of 10 vegan, 16 lacto-ovo vegetarian, and 16 healthy omnivorous women in the Boston metropolitan area. Six 3-day food records from each dietary group were analyzed for EAA content and estimated NAE, and correlations with measured urine pH were calculated. RESULTS: The mean (+/- SD) urine pH was 6.15 +/- 0.40 for vegans, 5.90 +/- 0.36 for lacto-ovo vegetarians, and 5.74 +/- 0.21 for omnivores (analysis of variance, P = .013). Calculated EAA values were not significantly different among the three groups, whereas mean estimated NAE values were significantly different: 17.3 +/- 14.5 mEq/day for vegans, 31.3 +/- 8.5 mEq/day for lacto-ovo vegetarians, and 42.6 +/- 13.2 mEq/day for omnivores (analysis of variance, P = .01). The average deattenuated correlation between urine pH and EAA was 0.333; this value was -0.768 for estimated NAE and urine pH, with a regression equation of pH = 6.33 - 0.014 NAE (P = .02, r = -0.54). CONCLUSIONS: Habitual diet and estimated NAE calculations indicate the probable ranking of urine pH by dietary groups, and may be used to determine the likely acid-base status of an individual; EAA calculations were not predictive of urine pH.","title":"Estimated net acid excretion inversely correlates with urine pH in vegans, lacto-ovo vegetarians, and omnivores."},{"docid":"MED-3235","text":"Background Maintaining muscle mass while aging is important to prevent falls and fractures. Metabolic acidosis promotes muscle wasting, and the net acid load from diets that are rich in net acid–producing protein and cereal grains relative to their content of net alkali–producing fruit and vegetables may therefore contribute to a reduction in lean tissue mass in older adults. Objective We aimed to determine whether there was an association of 24-h urinary potassium and an index of fruit and vegetable content of the diet with the percentage lean body mass (%LBM) or change in %LBM in older subjects. Design Subjects were 384 men and women ≥65 y old who participated in a 3-y trial comparing calcium and vitamin D with placebo. Potassium was measured in 24-h urine collections at baseline. The %LBM, defined as total body nonfat, nonbone tissue weight ÷ weight × 100, was measured by using dual-energy X-ray absorptiometry at baseline and at 3 y. Physical activity, height, and weight were assessed at baseline and at 3 y. Results At baseline, the mean urinary potassium excretion was 67.0 ± 21.1 mmol/d. Urinary potassium (mmol/d) was significantly positively associated with %LBM at baseline (β = 0.033, P = 0.006; adjusted for sex, weight, and nitrogen excretion) but not with 3-y change in %LBM. Over the 3-y study, %LBM increased by 2.6 ± 3.6%. Conclusion Higher intake of foods rich in potassium, such as fruit and vegetables, may favor the preservation of muscle mass in older men and women.","title":"Alkaline diets favor lean tissue mass in older adults"},{"docid":"MED-1618","text":"To study the effect of a moderate increase in insulin secretion produced by an increased daily protein intake on dehydroepiandrosterone sulfate (DHEAS), a balanced randomized crossover trial consisting of three strictly controlled dietary regimens was performed in six healthy male volunteers. The basic diet (B) contained 50 g protein/d; diets P and M (also basic diets) were enriched with either 32 g protein/d (P) or 10 mmol L-methionine/d (M). Methionine was given (as a specific nonprotein source of endogenously derived sulfate) to control for possible confounding effects on DHEAS due to an increased sulfate supply. At the end of each 4-day diet period, blood and 24-hour urine samples were collected. Fasting plasma levels of testosterone, cortisol, insulin-like growth factor-I (IGF-I), and insulin, as well as urinary output of total (hot acid-cleaved) testosterone conjugates and 3alpha-androstanediol glucuronide, did not show significant changes in response to dietary manipulations. Endogenous sulfate availability (as reflected by renal sulfate output per 24 hours) approximately doubled with diets P and M. However, plasma levels (6.3 +/- 1.5, 6.8 +/- 1.8, and 6.9 +/- 2.1 micromol/L for B, P, and M, respectively) and urinary excretion (8.8 +/- 9.8, 9.4 +/- 11.2, 8.0 +/- 8.3 micromol/d) of DHEAS remained unaffected. Considering the clear increments (P < .01) in urinary C-peptide excretion with diet P (20.4 +/- 10.3 nmol/d) versus diets B and M (12.6 +/- 5.1 and 13.2 +/- 3.6 nmol/d), respectively, our results suggest that a moderately strong diet-induced increase in daily insulin secretion does not alter urinary and plasma levels of DHEAS.","title":"A moderate increase in daily protein intake causing an enhanced endogenous insulin secretion does not alter circulating levels or urinary excretion..."},{"docid":"MED-2208","text":"BACKGROUND: Bikunin, a Kunitz-type protease inhibitor, specifically inhibits tumor invasion and metastasis. METHODS: The authors initially evaluated the therapeutic efficacy of once-daily oral administration of different doses of bikunin against human ovarian carcinoma HRA cells growing in the peritonea of nude mice. For the in vivo studies, female 7-week-old nude mice were randomized to 1 of 4 groups: bikunin-treated groups (n = 9 in each group) received 3, 10, or 30 microg/g body weight per day bikunin for 7 days via gastrointestinal gavage, and a control group (n = 9) received the vehicle solution (phosphate-buffered saline) via gastrointestinal gavage. On Day 9, the abdominal cavity was examined by two observers who were blinded to treatment. RESULTS: After oral administration, intact bikunin was detectable in mouse serum specimens at 3 and 6 hours. This was followed by a decline at 12 hours. The mice given bikunin at the highest dose level had a 40% decrease in tumor load. The highest uptake in the tumor was obtained with [125I]bikunin 12 hours postadministration. No effect on either food intake or body weight was observed in the treated versus sham groups. The current study was the first to report the potent activity of once-daily oral administration of bikunin against ovarian carcinoma. Next, the authors performed a Phase I trial to determine the maximum-tolerated dose (MTD) and safety of a once-daily oral administration schedule. The indication was locally advanced uterine cervical carcinoma after definitive treatment. An escalating dose (3, 10, and 30 mg/kg per day) of bikunin was administered orally to nine patients for 7 days. There were no dose-limiting toxicities and the MTD of the bikunin schedule was not defined. The authors also obtained preliminary data on its effect on urokinase-type plasminogen activator expression at the highest dose level. CONCLUSIONS: Once-daily oral administration of bikunin was found to be safe in humans and exhibited signs of biologic activity. Copyright 2004 American Cancer Society.","title":"Therapeutic efficacy of once-daily oral administration of a Kunitz-type protease inhibitor, bikunin, in a mouse model and in human cancer."},{"docid":"MED-1226","text":"Background Several components of dairy products have been linked to earlier menarche. Methods/Findings This study assessed whether positive associations exist between childhood milk consumption and age at menarche or the likelihood of early menarche (<12 yrs) in a U.S sample. Data derive from the National Health and Nutrition Examination Survey (NHANES) 1999–2004. Two samples were utilized: 2657 women age 20–49 yrs and 1008 girls age 9–12 yrs. In regression analysis, a weak negative relationship was found between frequency of milk consumption at 5–12 yrs and age at menarche (daily milk intake β = −0.32, P<0.10; “sometimes/variable milk intake” β = −0.38, P<0.06, each compared to intake rarely/never). Cox regression yielded no greater risk of early menarche among those who drank milk “sometimes/varied” or daily vs. never/rarely (HR: 1.20, P<0.42, HR: 1.25, P<0.23, respectively). Among the 9–12 yr olds, Cox regression indicated that neither total dairy kcal, calcium and protein, nor daily milk intake in the past 30 days contributed to early menarche. Girls in the middle tertile of milk intake had a marginally lower risk of early menarche than those in the highest tertile (HR: 0.6, P<0.06). Those in the lowest tertiles of dairy fat intake had a greater risk of early menarche than those in the highest (HR: 1.5, P<0.05, HR: 1.6, P<0.07, lowest and middle tertile, respectively), while those with the lowest calcium intake had a lower risk of early menarche (HR: 0.6, P<0.05) than those in the highest tertile. These relationships remained after adjusting for overweight or overweight and height percentile; both increased the risk of earlier menarche. Blacks were more likely than Whites to reach menarche early (HR: 1.7, P<0.03), but not after controlling for overweight. Conclusions There is some evidence that greater milk intake is associated with an increased risk of early menarche, or a lower age at menarche.","title":"Milk Intake and Total Dairy Consumption: Associations with Early Menarche in NHANES 1999-2004"},{"docid":"MED-2290","text":"Background Differences in nutrient profiles between vegetarian and non vegetarian dietary patterns reflect nutritional differences that may contribute to the development of disease. Objective To compare nutrient intakes between dietary patterns characterized by consumption or exclusion of meat and dairy products. Design Cross-sectional study of 71751 subjects (mean age 59 years) from the Adventist-Health-Study-2. Data was collected between 2002 and 2007. Participants completed a 204-item validated semi-quantitative food frequency questionnaire. Dietary patterns compared were: non vegetarian, semi vegetarian, pesco vegetarian, lacto-ovo vegetarian and strict vegetarian. ANCOVA was used to analyze differences in nutrient intakes by dietary patterns and were adjusted for age, and sex and race. BMI and other relevant demographic data were reported and compared by dietary pattern using chi-square tests and ANOVA. Results Many nutrient intakes varied significantly between dietary patterns. Non vegetarians had the lowest intakes of plant proteins, fiber, β-Carotene, and Mg than those following vegetarian dietary patterns and the highest intakes of saturated, trans, arachidonic, and docosahexaenoic fatty acids. The lower tails of some nutrient distributions in strict vegetarians suggested inadequate intakes by a portion of the subjects. Energy intake was similar among dietary patterns at close to 2000 kcal/d with the exception of semi vegetarians that had an intake of 1713 kcal/d. Mean BMI was highest in non-vegetarians (mean; standard deviation [SD]) (28.7; [6.4]) and lowest in strict vegetarians (24.0; [4.8]). Conclusions Nutrient profiles varied markedly between dietary patterns that were defined by meat and dairy intakes. These differences can be of interest in the etiology of obesity and chronic diseases.","title":"Nutrient Profiles of Vegetarian and Non Vegetarian Dietary Patterns"},{"docid":"MED-1722","text":"Overexpression of growth factors and/or their receptors is a common event in malignancy and provides the underlying mechanisms for one of the hallmarks of cancer, uncontrolled proliferation. Mounting evidence suggests that IGF-1 is involved in the pathogenesis and progression of different types of human cancer such as colon, breast, prostate and lung. However, only a few studies have investigated the association between IGF-1 levels and childhood cancer risk. We aimed to compare the IGF-1 serum level in children with de novo malignancies to healthy children, and to assess its relationship with cancer type, stage, metastasis and different disease characteristics. The study was carried out on 100 children; 50 children with de novo malignancies and 50 healthy children of matched age and gender as a control group. The patients were subjected to a routine work-up for their cancers according to our local standards. Estimation of the serum level of IGF-1 was carried out in the two groups using ELISA. Our results showed that children with cancer had significantly higher levels of IGF-1 than healthy controls of the same age and gender. No association was found between IGF-1 and tumor type, stage, metastasis and other disease characteristics. In conclusion, the IGF-1 serum level is an important indicator of risk for the most prevalent forms of childhood cancer. It may be used to identify children at the highest risk for these cancers and aid in determing who may benefit most from preventive strategies. Given the small number of children in our study, studies with larger populations are required to confirm these results.","title":"Insulin-like growth factor-1 and childhood cancer risk"},{"docid":"MED-2649","text":"Background Dietary fat exerts numerous complex effects on proinflammatory and immunologic pathways. Several epidemiological studies have examined the relationships between intake of fatty acids and/or foods high in fat and allergic rhinitis, but have provided conflicting findings. The current cross-sectional study investigated such relationships in Japan. Methods Study subjects were 1745 pregnant women. The definition of rhinoconjunctivitis was based on criteria from the International Study of Asthma and Allergies in Childhood. Information on dietary factors was collected using a validated self-administered diet history questionnaire. Adjustment was made for age; gestation; region of residence; number of older siblings; number of children; smoking; secondhand smoke exposure at home and at work; family history of asthma, atopic eczema, and allergic rhinitis; household income; education; and body mass index. Results The prevalence of rhinoconjunctivitis in the past 12 months was 25.9%. Higher meat intake was significantly associated with an increased prevalence of rhinoconjunctivitis: the adjusted odds ratio between extreme quartiles was 1.71 (95% confidence interval: 1.25-2.35, P for trend = 0.002). No measurable association was found between fish intake and rhinoconjunctivitis. Intake of total fat, saturated fatty acids, monounsaturated fatty acids, n-3 polyunsaturated fatty acids, α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, n-6 polyunsaturated fatty acids, linoleic acid, arachidonic acid, and cholesterol and the ratio of n-3 to n-6 polyunsaturated fatty acid intake were not evidently related to the prevalence of rhinoconjunctivitis. Conclusions The current results suggest that meat intake may be positively associated with the prevalence of rhinoconjunctivitis in young adult Japanese women.","title":"Dietary meat and fat intake and prevalence of rhinoconjunctivitis in pregnant Japanese women: baseline data from the Kyushu Okinawa Maternal and Child Health Study"},{"docid":"MED-2646","text":"BACKGROUND: Certain foods may increase or decrease the risk of developing asthma, rhinoconjunctivitis and eczema. We explored the impact of the intake of types of food on these diseases in Phase Three of the International Study of Asthma and Allergies in Childhood. METHODS: Written questionnaires on the symptom prevalence of asthma, rhinoconjunctivitis and eczema and types and frequency of food intake over the past 12 months were completed by 13-14-year-old adolescents and by the parents/guardians of 6-7-year-old children. Prevalence ORs were estimated using logistic regression, adjusting for confounders, and using a random (mixed) effects model. RESULTS: For adolescents and children, a potential protective effect on severe asthma was associated with consumption of fruit ≥3 times per week (OR 0.89, 95% CI 0.82 to 0.97; OR 0.86, 95% CI 0.76 to 0.97, respectively). An increased risk of severe asthma in adolescents and children was associated with the consumption of fast food ≥3 times per week (OR 1.39, 95% CI 1.30 to 1.49; OR 1.27, 95% CI 1.13 to 1.42, respectively), as well as an increased risk of severe rhinoconjunctivitis and severe eczema. Similar patterns for both ages were observed for regional analyses, and were consistent with gender and affluence categories and with current symptoms of all three conditions. CONCLUSIONS: If the association between fast foods and the symptom prevalence of asthma, rhinoconjunctivitis and eczema is causal, then the findings have major public health significance owing to the rising consumption of fast foods globally.","title":"Do fast foods cause asthma, rhinoconjunctivitis and eczema? Global findings from the International Study of Asthma and Allergies in Childhood (ISAA..."},{"docid":"MED-1610","text":"The effects of three different meat-containing breakfast meals (pork, beef or chicken) on acute satiety and appetite regulatory hormones were compared using a within-subjects study design. Thirty fasting non-smoking pre-menopausal women attended a research centre on three test days to consume, a meat-containing meal matched in energy (kJ) and protein content, palatability, and appearance. No difference was found between meat groups for either energy intake or macronutrient profile of food consumed at a subsequent ad libitum buffet lunch, or over the rest of the day. Visual Analogue Scale (VAS) ratings for hunger and satiety over an 180 min period did not differ between test meals. After consumption of the test meals, a significant difference was found in PYY response between pork and chicken meals (P=0.027) but not for levels of CCK, ghrelin, insulin or glucose. This study positions pork, beef, and chicken as equal in their effect on satiety and release of appetite-related intestinal hormones and of insulin. Copyright © 2010 Elsevier Ltd. All rights reserved.","title":"Pork, beef and chicken have similar effects on acute satiety and hormonal markers of appetite."},{"docid":"MED-3464","text":"The purpose of this study was to determine the effects of consuming sweet cherries on plasma lipids and markers of inflammation in healthy humans. Healthy men and women (n = 18) supplemented their diets with Bing sweet cherries (280 g/d) for 28 d. After a 12-h fast, blood samples were taken before the start of cherry consumption (study d 0 and 7), 14 and 28 d after the start of cherry supplementation (study d 21 and 35), and 28 d after the discontinuation (study d 64) of cherry consumption. After cherries were consumed for 28 d, circulating concentrations of C-reactive protein (CRP), regulated upon activation, normal T-cell expressed, and secreted (RANTES), and NO decreased by 25 (P < 0.05), 21 (P < 0.05), and 18% (P = 0.07) respectively. After the discontinuation of cherry consumption for 28 d (d 64), concentrations of RANTES continued to decrease (P = 0.001), whereas those of CRP and NO did not differ from either d 7 (pre-cherries) or d 35 (post-cherries). Plasma concentrations of IL-6 and its soluble receptor, intercellular adhesion molecule-1, and tissue inhibitor of metalloproteinases-2 did not change during the study. Cherry consumption did not affect the plasma concentrations of total-, HDL-, LDL-, and VLDL- cholesterol, triglycerides, subfractions of HDL, LDL, VLDL, and their particle sizes and numbers. It also did not affect fasting blood glucose or insulin concentrations or a number of other chemical and hematological variables. Results of the present study suggest a selective modulatory effect of sweet cherries on CRP, NO, and RANTES. Such anti-inflammatory effects may be beneficial for the management and prevention of inflammatory diseases.","title":"Consumption of Bing sweet cherries lowers circulating concentrations of inflammation markers in healthy men and women."},{"docid":"MED-2362","text":"The study of the expression of Gal alpha 1----3Gal beta 1----4GlcNAc residues on mammalian glycoconjugates is of particular interest since as many as 1% of circulating IgG antibodies in man (the natural anti-Gal antibody) interact specifically with this carbohydrate residue. In recent studies, we have found that Gal alpha 1----3Gal beta 1----4GlcNAc residues are abundant on red cells and nucleated cells of nonprimate mammals, prosimians, and New World monkeys, but their expression is diminished in Old World monkeys, apes, and humans. In the present work, we have analyzed the expression of these residues on secreted mammalian glycoproteins. For this purpose, we have developed a radioimmunoassay (RIA) which enables the quantification of Gal alpha 1----3Gal beta 1----4GlcNAc residues on the secreted glycoproteins. Purified biotinylated anti-Gal was used as the antibody in the RIA, and bovine thyroglobulin enriched for Gal alpha 1----3Gal beta 1----4GlcNAc residues served as a solid-phase antigen. In this study, it is reported for the first time that the evolutionary pattern of Gal alpha 1----3Gal beta 1----4GlcNAc residue distribution in in vivo secreted glycoproteins is similar to that observed in membranes of cell lines and of red cells. Thyroglobulin, fibrinogen, or IgG molecules from nonprimate mammals and from New World monkeys express varying amounts of Gal alpha 1----3Gal beta 1----4GlcNAc residues ranging between 0.01 and 11 residues per molecule, whereas no such residues are present on any of these glycoproteins of human or Old World monkey origin.(ABSTRACT TRUNCATED AT 250 WORDS)","title":"Distribution of Gal alpha 1----3Gal beta 1----4GlcNAc residues on secreted mammalian glycoproteins (thyroglobulin, fibrinogen, and immunoglobulin G..."},{"docid":"MED-3149","text":"Many health conditions are treated, at least in part, by therapeutic diets. Although the success of any intervention depends on its acceptability to the patient, the acceptability of therapeutic diets and factors that influence it have been largely neglected in nutrition research. A working definition of acceptability is proposed and an examination and summary are provided of available data on the acceptability of common diet regimens used for medical conditions. The goal is to suggest ways to improve the success of therapeutic diets. The proposed working definition of \"acceptability\" refers to the user's judgment of the advantages and disadvantages of a therapeutic diet-in relation to palatability, costs, and effects on eating behaviour and health-that influence the likelihood of adherence. Very low-calorie, reduced-fat omnivorous, vegetarian and vegan, and low-carbohydrate diets all achieve acceptability among the majority of users in studies of up to one year, in terms of attrition and adherence rates and results of questionnaires assessing eating behaviours. Longer studies are fewer, but they suggest that vegetarian, vegan, and reduced-fat diets are acceptable, as indicated by sustained changes in nutrient intake. Few studies of this length have been published for very low-calorie or low-carbohydrate diets. Long-term studies of adherence and acceptability of these and other therapeutic diets are warranted.","title":"Four therapeutic diets: adherence and acceptability."},{"docid":"MED-3774","text":"While dehydration has well-documented negative effects on adult cognition, there is little research on hydration and cognitive performance in children. We investigated whether having a drink of water improved children's performance on cognitive tasks. Fifty-eight children aged 7-9 years old were randomly allocated to a group that received additional water or a group that did not. Results showed that children who drank additional water rated themselves as significantly less thirsty than the comparison group (p=0.002), and they performed better on visual attention tasks (letter cancellation, p=0.02; spot the difference memory tasks, ps=0.019 and 0.014).","title":"Should children drink more water?: the effects of drinking water on cognition in children."},{"docid":"MED-2763","text":"Despite compelling statistics that show we could eliminate 80%of all heart disease and strokes, 90% of all diabetes, and 60% of all cancers with basic lifestyle changes, we have failed to motivate the public to make these changes and failed to motivate policy makers to make healthy choices the easiest choice. Dr. Katz suggests we have failed because we have focused too much on statistics and too little on passion. He implores all of us to tap into people's passion by connecting each of these statistics with a human story.","title":"Facing the facelessness of public health: what's the public got to do with it?"},{"docid":"MED-2291","text":"PURPOSE: This review focuses on the health benefits of viscous versus nonviscous soluble fibers, why symptoms can occur with increased fiber consumption, and how to avoid symptoms to improve adherence with a high-fiber diet. DATA SOURCES: Review of scientific literature as well as evidence-based guidelines and resources. CONCLUSIONS: While it is generally known that \"fiber is good for you,\" it is less well known that specific health benefits are associated with specific fiber characteristics. Many of the health benefits of fiber can be directly correlated with the viscosity of soluble fibers when hydrated (i.e., gel-forming). A reduction in viscosity of a given fiber will attenuate these health benefits, and a nonviscous fiber does not exhibit these health benefits. IMPLICATIONS FOR PRACTICE: Increasing the viscosity of chyme with a viscous soluble fiber has been shown clinically to lower cholesterol for cardiovascular health, improve glycemic control in type 2 diabetes, normalize stool form in both constipation (softens hard stool) and diarrhea (firms loose/liquid stool), and improve the objective clinical measures of metabolic syndrome (glycemic control, lipoprotein profile, body mass index/weight loss, and blood pressure). ©2012 The Author(s) Journal compilation ©2012 American Academy of Nurse Practitioners.","title":"Viscous versus nonviscous soluble fiber supplements: mechanisms and evidence for fiber-specific health benefits."},{"docid":"MED-3457","text":"Reactive oxygen species produced during vigorous exercise may permeate into cell nuclei and induce oxidative DNA damage, but the supporting evidence is still lacking. By using a 42 km marathon race as a model of massive aerobic exercise, we demonstrated a significant degree of unrepaired DNA base oxidation in peripheral immunocompetent cells, despite a concurrent increase in the urinary excretion of 8-hydroxy-2'-deoxyguanosine. Single cell gel electrophoresis with the incorporation of lesion-specific endonucleases further revealed that oxidized pyrimidines (endonuclease III-sensitive sites) contributed to most of the postexercise nucleotide oxidation. The oxidative DNA damage correlated significantly with plasma levels of creatinine kinase and lipid peroxidation metabolites, and lasted for more than 1 week following the race. This phenomenon may be one of the mechanisms behind the immune dysfunctions after exhaustive exercise.","title":"Oxidative DNA damage in human peripheral leukocytes induced by massive aerobic exercise."},{"docid":"MED-4290","text":"BACKGROUND AND AIMS: Nut intake has been inversely related to body mass index (BMI) in prospective studies. We examined dietary determinants of adiposity in an elderly Mediterranean population with customarily high nut consumption. METHODS AND RESULTS: A cross-sectional study was conducted in 847 subjects (56% women, mean age 67 years, BMI 29.7kg/m(2)) at high cardiovascular risk recruited into the PREDIMED study. Food consumption was evaluated by a validated semi-quantitative questionnaire, energy expenditure in physical activity by the Minnesota Leisure Time Activity questionnaire, and anthropometric variables by standard measurements. Nut intake decreased across quintiles of both BMI and waist circumference (P-trend <0.005; both). Alcohol ingestion was inversely related to BMI (P-trend=0.020) and directly to waist (P-trend=0.011), while meat intake was directly associated with waist circumference (P-trend=0.018). In fully adjusted multivariable models, independent dietary associations of BMI were the intake of nuts inversely (P=0.002) and that of meat and meat products directly (P=0.042). For waist circumference, independent dietary associations were intake of nuts (P=0.002) and vegetables (P=0.040), both inversely, and intake of meat and meat products directly (P=0.009). From the regression coefficients, it was predicted that BMI and waist circumference decreased by 0.78kg/m(2) and 2.1cm, respectively, for each serving of 30g of nuts. Results were similar in men and women. CONCLUSION: Nut consumption was inversely associated with adiposity independently of other lifestyle variables. It remains to be explored whether residual confounding related to a healthier lifestyle of nut eaters might in part explain these results. Copyright © 2009 Elsevier B.V. All rights reserved.","title":"Cross-sectional association of nut intake with adiposity in a Mediterranean population."},{"docid":"MED-3314","text":"OBJECTIVES: Evidence suggests that certain occupations and related exposures may increase the risk of malignant lymphoma. Farming, printing and paper industry, wood processing, meat handling and processing, welding, shoe and leather manufacturing and teaching profession are among the categories that have been implicated in previous studies. The relationship between occupation and malignant lymphoma has been investigated in a large European prospective study. METHODS: We investigated occupational risks for lymphomas in the European Prospective Investigation into Cancer and Nutrition (EPIC). The mean follow-up time for 348,555 subjects was 9 years (SD: 2 years). The analysis was based on 866 and 48 newly diagnosed cases of non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL). These were identified in the EPIC subcohorts with occupational data. Data on 52 occupations were collected through standardised questionnaires. Cox proportional hazard models were used to explore the association between occupation and risk of malignant lymphoma. RESULTS: The following occupations were positively associated with malignant NHL after adjustment for study centre, age, sex, socioeconomic status (SES), smoking and alcohol: butchers (HR=1.53, 95% CI 1.05 to 2.48, including multiple myeloma/plasmacytoma; HR=1.30, 95% CI 1.00 to 2.66, excluding multiple myeloma/plasmacytoma) and car repair workers (HR=1.50, 95% CI 1.01 to 2.00, including multiple myeloma/plasmacytoma; HR=1.51, 95% CI 1.01 to 2.31, excluding multiple myeloma/plasmacytoma). HL was associated with gasoline station occupation (HR=4.59, 95% CI 1.08 to 19.6). CONCLUSION: The findings in this current study of a higher risk of NHL among car repair workers and butchers and a higher risk of HL among gasoline station workers suggest a possible role from occupationally related exposures, such as solvents and zoonotic viruses, as risk factors for malignant lymphoma.","title":"Occupation and risk of lymphoma: a multicentre prospective cohort study (EPIC)."},{"docid":"MED-3135","text":"Background: Only 5% of all breast cancers are the result of BRCA1/2 mutations. Methylation silencing of tumor suppressor genes is well described in sporadic breast cancer; however, its role in familial breast cancer is not known. Methods: CpG island promoter methylation was tested in the initial random periareolar fine-needle aspiration sample from 109 asymptomatic women at high risk for breast cancer. Promoter methylation targets included RARB (M3 and M4), ESR1, INK4a/ARF, BRCA1, PRA, PRB, RASSF1A, HIN-1, and CRBP1. Results: Although the overall frequency of CpG island promoter methylation events increased with age (P < 0.0001), no specific methylation event was associated with age. In contrast, CpG island methylation of RARB M4 (P = 0.051), INK4a/ARF (P = 0.042), HIN-1 (P = 0.044), and PRA (P = 0.032), as well as the overall frequency of methylation events (P = 0.004), was associated with abnormal Masood cytology. The association between promoter methylation and familial breast cancer was tested in 40 unaffected premenopausal women in our cohort who underwent BRCA1/2 mutation testing. Women with BRCA1/2 mutations had a low frequency of CpG island promoter methylation (15 of 15 women had ≤4 methylation events), whereas women without a mutation showed a high frequency of promoter methylation events (24 of 25 women had 5-8 methylation events; P < 0.0001). Of women with a BRCA1/2 mutation, none showed methylation of HIN-1 and only 1 of 15 women showed CpG island methylation of RARB M4, INK4a/ARF, or PRB promoters. Conclusions: This is the first evidence of CpG island methylation of tumor suppressor gene promoters in non-BRCA1/2 familial breast cancer.","title":"CpG Island Tumor Suppressor Promoter Methylation in Non-BRCA-Associated Early Mammary Carcinogenesis"},{"docid":"MED-4559","text":"The cardiovascular risk reduction associated with different statins for the prevention of cardiovascular disease and the cardiovascular risk increase associated with excess dietary intake of fat have been quantified. However, these relative risks have never been directly juxtaposed to determine whether an increase in relative risk by 1 activity could be neutralized by an opposing change in relative risk from a second activity. The investigators compared the increase in relative risk for cardiovascular disease associated with the total fat and trans fat content of fast foods against the relative risk decrease provided by daily statin consumption from a meta-analysis of statins in primary prevention of coronary artery disease (7 randomized controlled trials including 42,848 patients). The risk reduction associated with the daily consumption of most statins, with the exception of pravastatin, is more powerful than the risk increase caused by the daily extra fat intake associated with a 7-oz hamburger (Quarter Pounder) with cheese and a small milkshake. In conclusion, statin therapy can neutralize the cardiovascular risk caused by harmful diet choices. In other spheres of human activity, individuals choosing risky pursuits (motorcycling, smoking, driving) are advised or compelled to use measures to minimize the risk (safety equipment, filters, seatbelts). Likewise, some individuals eat unhealthily. Routine accessibility of statins in establishments providing unhealthy food might be a rational modern means to offset the cardiovascular risk. Fast food outlets already offer free condiments to supplement meals. A free statin-containing accompaniment would offer cardiovascular benefits, opposite to the effects of equally available salt, sugar, and high-fat condiments. Although no substitute for systematic lifestyle improvements, including healthy diet, regular exercise, weight loss, and smoking cessation, complimentary statin packets would add, at little cost, 1 positive choice to a panoply of negative ones.","title":"Can a statin neutralize the cardiovascular risk of unhealthy dietary choices?"},{"docid":"MED-3348","text":"Fruit and vegetable consumption is inadequate among adults in the United States; this contributes to preventable morbidity and mortality. More effective dietary intervention strategies are needed. Recently, interventions that advertise the consequences of behavior for appearance have been successful in modifying sun-exposure habits and tobacco use. Such an approach might also facilitate dietary improvement. Consumption of carotenoid-rich fruit and vegetables positively affects skin color, which influences perceptions of health and attractiveness, and promoting such an effect may motivate target audiences to increase consumption of this important food group. This approach represents a novel direction for the field and is potentially suitable for cost-effective, population-level dissemination through the visual media.","title":"Appealing to Vanity: Could Potential Appearance Improvement Motivate Fruit and Vegetable Consumption?"},{"docid":"MED-2336","text":"Accumulated evidence shows that some phytochemicals provide beneficial effects for human health. Recently, a number of mechanistic studies have revealed that direct interactions between phytochemicals and functional proteins play significant roles in exhibiting their bioactivities. However, their binding selectivities to biological molecules are considered to be lower due to their small and simple structures. In this study, we found that zerumbone, a bioactive sesquiterpene, binds to numerous proteins with little selectivity. Similar to heat-denatured proteins, zerumbone-modified proteins were recognized by heat shock protein 90, a constitutive molecular chaperone, leading to heat shock factor 1-dependent heat shock protein induction in hepa1c1c7 mouse hepatoma cells. Furthermore, oral administration of this phytochemical up-regulated heat shock protein expressions in the livers of Sprague-Dawley rats. Interestingly, pretreatment with zerumbone conferred a thermoresistant phenotype to hepa1c1c7 cells as well as to the nematode Caenorhabditis elegans. It is also important to note that several phytochemicals with higher hydrophobicity or electrophilicity, including phenethyl isothiocyanate and curcumin, markedly induced heat shock proteins, whereas most of the tested nutrients did not. These results suggest that non-specific protein modifications by xenobiotic phytochemicals cause mild proteostress, thereby inducing heat shock response and leading to potentiation of protein quality control systems. We considered these bioactivities to be xenohormesis, an adaptation mechanism against xenobiotic chemical stresses. Heat shock response by phytochemicals may be a fundamental mechanism underlying their various bioactivities.","title":"Non-Specific Protein Modifications by a Phytochemical Induce Heat Shock Response for Self-Defense"},{"docid":"MED-4920","text":"BACKGROUND: Celiac disease (CD) is an immune-mediated enteropathic condition triggered in genetically susceptible individuals by the ingestion of gluten. Although common in Europe, CD is thought to be rare in the United States, where there are no large epidemiologic studies of its prevalence. The aim of this study was to determine the prevalence of CD in at-risk and not-at-risk groups in the United States. METHODS: Serum antigliadin antibodies and anti-endomysial antibodies (EMA) were measured. In EMA-positive subjects, human tissue transglutaminase IgA antibodies and CD-associated human leukocyte antigen DQ2/DQ8 haplotypes were determined. Intestinal biopsy was recommended and performed whenever possible for all EMA-positive subjects. A total of 13 145 subjects were screened: 4508 first-degree and 1275 second-degree relatives of patients with biopsy-proven CD, 3236 symptomatic patients (with either gastrointestinal symptoms or a disorder associated with CD), and 4126 not-at-risk individuals. RESULTS: In at-risk groups, the prevalence of CD was 1:22 in first-degree relatives, 1:39 in second-degree relatives, and 1:56 in symptomatic patients. The overall prevalence of CD in not-at-risk groups was 1:133. All the EMA-positive subjects who underwent intestinal biopsy had lesions consistent with CD. CONCLUSIONS: Our results suggest that CD occurs frequently not only in patients with gastrointestinal symptoms, but also in first- and second-degree relatives and patients with numerous common disorders even in the absence of gastrointestinal symptoms. The prevalence of CD in symptomatic patients and not-at-risk subjects was similar to that reported in Europe. Celiac disease appears to be a more common but neglected disorder than has generally been recognized in the United States.","title":"Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: a large multicenter study."},{"docid":"MED-1719","text":"OBJECTIVE: Overexpression of IGF-I occurs in tumors diagnosed in childhood (osteosarcoma, Wilms tumor, neuroblastoma, etc.) and in adults (breast, ovaries, colon and prostate cancer). The aim of our study was to establish the prevalence of malignancies in states of congenital IGF-I deficiency. SUBJECTS: We surveyed 222 patients with congenital IGF-I deficiency (Laron syndrome, GH gene deletion, GHRH receptor defects and IGF-I resistance) and 338 first and second-degree relatives. RESULTS: None of the IGF-I deficient patients had cancer, whereas 9-24% of the family members had a history of malignancy. CONCLUSIONS: Congenital IGF-I deficiency acts as a protecting factor for the development of cancer.","title":"Patients with congenital deficiency of IGF-I seem protected from the development of malignancies: a preliminary report."},{"docid":"MED-1613","text":"The present study was designed to examine the effects of habitual consumption of Taiwanese vegetarian diets on hormonal secretion, and on lipid and glycaemic control. Of the ninety-eight healthy female adults recruited from Hualien, Taiwan (aged 31-45 years), forty-nine were Buddhist lactovegetarians and forty-nine were omnivores. Dietary intakes were measured, and blood levels of nutrients and hormones were analysed. Vegetarians consumed less energy, fat and protein, but more fibre than the omnivores. Compared with the omnivores, the vegetarians had, on average, lower BMI and smaller waist circumference. Except for slightly lower levels of thyroxine (T4) in vegetarians, vegetarians and omnivores both showed similar levels of triiodothyronine (T3), free T4, thyroid-stimulating hormone, T3:T4 ratio and cortisol. Compared with the omnivores, the vegetarians had significantly lower levels of fasting insulin (median: 35.3 v. 50.6 pmol/l) and plasma glucose (mean: 4.7 (se 0.05) v. 4.9 (se 0.05) mmol/l). Insulin resistance, as calculated by the homeostasis model assessment method, was significantly lower in the vegetarians than in the omnivores (median: 1.10 v. 1.56), while beta-cell function was not different between the two groups. BMI and diet were both independent predictors for insulin resistance, and contributed 18 and 15 % of the variation in insulin resistance, respectively. In conclusion, Taiwanese vegetarians had lower glucose and insulin levels and higher insulin sensitivity than did the omnivores. Diet and lower BMI were partially responsible for the high insulin sensitivity observed in young Taiwanese vegetarians.","title":"Taiwanese vegetarians have higher insulin sensitivity than omnivores."},{"docid":"MED-1185","text":"Endogenous sulfite is generated as a consequence of the body's normal processing of sulfur-containing amino acids. Sulfites occur as a consequence of fermentation and also occur naturally in a number of foods and beverages. As food additives, sulfiting agents were first used in 1664 and approved in the United States as long ago as the 1800s. With such long experience with their use, it is easy to understand why these substances have been regarded as safe. They are currently used for a variety of preservative properties, including controlling microbial growth, preventing browning and spoilage, and bleaching some foods. It is estimated that up to 500,000 (< .05% of the population) sulfite-sensitive individuals live in the United States. Sulfite sensitivity occurs most often in asthmatic adults--predominantly women; it is uncommonly reported in preschool children. Adverse reactions to sulfites in nonasthmatics are extremely rare. Asthmatics who are steroid-dependent or who have a higher degree of airway hyperreactivity may be at greater risk of experiencing a reaction to sulfite-containing foods. Even within this limited population, sulfite sensitivity reactions vary widely, ranging from no reaction to severe. The majority of reactions are mild. These manifestations may include dermatologic, respiratory, or gastrointestinal signs and symptoms. Severe nonspecific signs and symptoms occur less commonly. Broncho-constriction is the most common sensitivity response in asthmatics. The precise mechanisms of the sensitivity responses have not been completely elucidated. Inhalation of sulfur dioxide (SO2) generated in the stomach following ingestion of sulfite-containing foods or beverages, a deficiency in a mitochondrial enzyme, and an IgE-mediated immune response have all been implicated.(ABSTRACT TRUNCATED AT 250 WORDS)","title":"Sulfite sensitivity: significance in human health."},{"docid":"MED-1614","text":"AIM: To compare the insulin sensitivity indices between Chinese vegetarians and omnivores. METHODS: The study included 36 healthy volunteers (vegetarian, n=19; omnivore, n=17) who had normal fasting plasma glucose levels. Each participant completed an insulin suppression test. We compared steady-state plasma glucose (SSPG), fasting insulin, the homeostasis model assessment for insulin sensitivity (HOMA-IR and HOMA %S) and beta-cell function (HOMA %beta) between the groups. We also tested the correlation of SSPG with years on a vegetarian diet. RESULTS: The omnivore subjects were younger than the vegetarians (55.7+/-3.7 vs 58.6+/-3.6 year of age, P=0.022). There was no difference between the two groups in sex, blood pressure, renal function tests and lipid profiles. The omnivores had higher serum uric acid levels than vegetarians (5.25+/-0.84 vs 4.54+/-0.75 mg/dl, P=0.011). The results of the indices were different between omnivores and vegetarians (SSPG (mean+/-s.d.) 105.4+/-10.2 vs 80.3+/-11.3 mg/dl, P<0.001; fasting insulin, 4.06+/-0.77 vs 3.02+/-1.19 microU/ml, P=0.004; HOMA-IR, 6.75+/-1.31 vs 4.78+/-2.07, P=0.002; HOMA %S, 159.2+/-31.7 vs 264.3+/-171.7%, P=0.018) except insulin secretion index, HOMA %beta (65.6+/-18.0 vs 58.6+/-14.8%, P=0.208). We found a clear linear relation between years on a vegetarian diet and SSPG (r=-0.541, P=0.017). CONCLUSIONS: The vegetarians were more insulin sensitive than the omnivore counterparts. The degree of insulin sensitivity appeared to be correlated with years on a vegetarian diet.","title":"Insulin sensitivity in Chinese ovo-lactovegetarians compared with omnivores."},{"docid":"MED-3277","text":"Methionine dependence is a metabolic defect that occurs in many human tumor cell lines but not normal in unestablished cell strains. Methionine-dependent tumor cell lines are unable to proliferate and arrest in the late S/G2 phase of the cell cycle when methionine is replaced by its immediate precursor homocysteine in the culture medium (MET-HCY+ medium). However, it is not known whether methionine dependence occurs in fresh patient tumors as it does in cell lines. In order to determine whether methionine dependence occurs in fresh patient tumors as well as whether methionine dependence occurs in fresh patient tumors as well as in cell lines we took advantage of the technique of sponge-gel-supported histoculture to grow tumors directly from surgery. We then measured nuclear DNA content by image analysis to determine the cell cycle position in MET-HCY+ compared to MET+HCY- medium in 21 human patient tumors. Human tumor cell lines found to be methionine dependent by cell count were used as positive controls and were found to have marked reduction of cells in G1 compared to total cells in the cell cycle in MET-HCY+ medium with respect to the G1: total cell ratio in MET+HCY- medium. Therefore late cell cycle arrest was used as a marker of methionine dependence for histocultured patient tumors. We found that 5 human tumors of 21, including tumors of the colon, breast, ovary, prostate, and a melanoma, were methionine dependent based on cell cycle analysis. These data on fresh human tumors indicate that methionine dependence may frequently occur in the cancer patient population. Implications for potential therapy based on methionine dependence are discussed.","title":"Expression of the biochemical defect of methionine dependence in fresh patient tumors in primary histoculture."},{"docid":"MED-2276","text":"A limited number of studies have demonstrated that some modulators of inflammation can be altered by the consumption of sweet cherries. We have taken a proteomics approach to determine the effects of dietary cherries on targeted gene expression. The purpose was then to determine changes caused by cherry consumption in the plasma concentrations of multiple biomarkers for several chronic inflammatory diseases in healthy humans with modestly elevated C-reactive protein (CRP; range, 1-14 mg/L; mean, 3.5 mg/L; normal, <1.0 mg/L). Eighteen men and women (45-61 y) supplemented their diets with Bing sweet cherries (280 g/d) for 28 d. Fasting blood samples were taken before the start of consuming the cherries (study d 7), 28 d after the initiation of cherry supplementation (d 35), and 28 d after the discontinuation (d 63). Of the 89 biomarkers assessed, cherry consumption for 28 d altered concentrations of 9, did not change those of 67, and the other 13 were below the detection limits. Cherry consumption decreased (P < 0.05) plasma concentrations of extracellular newly identified ligand for the receptor for advanced glycation end products (29.0%), CRP (20.1%), ferritin (20.3%), plasminogen activator inhibitor-1 (19.9%), endothelin-1 (13.7%), epidermal growth factor (13.2%), and IL-18 (8.1%) and increased that of IL-1 receptor antagonist (27.9%) compared with corresponding values on study d 7. The ferritin concentration continued to decrease between d 35 and 63 and it was significantly lower on d 63 than on d 7. Because the participants in this study were healthy, no clinical pathology end points were measured. However, results from the present study demonstrate that cherry consumption selectively reduced several biomarkers associated with inflammatory diseases.","title":"Sweet bing cherries lower circulating concentrations of markers for chronic inflammatory diseases in healthy humans."},{"docid":"MED-1223","text":"OBJECTIVE: To assess the life history consequences of cow milk consumption at different stages in early life (prenatal to adolescence), especially with regard to linear growth and age at menarche and the role of insulin-like growth factor I (IGF-I) in mediating a relationship among milk, growth and development, and long-term biological outcomes. METHODS: United States National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2004 and review of existing literature. RESULTS: The literature tends to support milk's role in enhancing growth early in life (prior to age 5 years), but there is less support for this relationship during middle childhood. Milk has been associated with early menarche and with acceleration of linear growth in adolescence. NHANES data show a positive relationship between milk intake and linear growth in early childhood and adolescence, but not middle childhood, a period of relatively slow growth. IGF-I is a candidate bioactive molecule linking milk consumption to more rapid growth and development, although the mechanism by which it may exert such effects is unknown. CONCLUSIONS: Routine milk consumption is an evolutionarily novel dietary behavior that has the potential to alter human life history parameters, especially vis-à-vis linear growth, which in turn may have negative long-term biological consequences. Copyright © 2011 Wiley Periodicals, Inc.","title":"Cow milk consumption, insulin-like growth factor-I, and human biology: a life history approach."},{"docid":"MED-2368","text":"BACKGROUND: Microparticles (MPs) with procoagulant activity are present in human atherosclerosis, but no detailed information is available on their composition. METHODS AND RESULTS: To obtain insights into the role of MPs in atherogenesis, MP proteins were identified by tandem mass spectrometry, metabolite profiles were determined by high-resolution nuclear magnetic resonance spectroscopy, and antibody reactivity was assessed against combinatorial antigen libraries. Plaque MPs expressed surface antigens consistent with their leukocyte origin, including major histocompatibility complex classes I and II, and induced a dose-dependent stimulatory effect on T-cell proliferation. Notably, taurine, the most abundant free organic acid in human neutrophils, which scavenges myeloperoxidase-catalyzed free radicals, was highly enriched in plaque MPs. Moreover, fluorescent labeling of proteins on the MP surface suggested immunoglobulins to be trapped inside, which was confirmed by flow cytometry analysis on permeabilized and nonpermeabilized plaque MPs. Colabeling for CD14 and IgG established that more than 90% of the IgG containing MPs were CD14(+), indicating a macrophage origin. Screening against an antigen library revealed that the immunologic profiles of antibodies in MPs were similar to those found in plaques but differed profoundly from antibodies in plasma and unexpectedly, showed strong reactions with oligosaccharide antigens, in particular blood group antigen A. CONCLUSIONS: This study provides the first evidence that immunoglobulins are present within MPs derived from plaque macrophages, that the portfolio of plaque antibodies is different from circulating antibodies in plasma, and that anticarbohydrate antibodies are retained in human atherosclerotic lesions.","title":"Proteomics, metabolomics, and immunomics on microparticles derived from human atherosclerotic plaques."},{"docid":"MED-2468","text":"BACKGROUND AND METHODS: We estimated the prevalence of self-reported asthma in adult Indians and examined several risk factors influencing disease prevalence. Analysis is based on 99 574 women and 56 742 men aged 20–49 years included in India’s third National Family Health Survey, 2005–2006. Multiple logistic regression analysis was used to estimate the prevalence odds ratios for asthma, adjusting for various risk factors. RESULTS: The prevalence of self-reported asthma was 1.8% (95%CI 1.6–2.0) among men and 1.9% (95%CI 1.8–2.0) among women, with higher rates in rural than in urban areas and marked geographic differences. After adjustment for known asthma risk factors, women were 1.2 times more likely to have asthma than men. Daily/weekly consumption of milk/milk products, green leafy vegetables and fruits were associated with a lower asthma risk, whereas consumption of chicken/meat, a lower body mass index (BMI; <16 kg/m2, OR 2.08, 95%CI 1.73–2.50) as well as a higher BMI (>30 kg/m2, OR 1.67, 95%CI 1.36–2.06), current tobacco smoking (OR 1.30, 95%CI 1.12–1.50) and ever use of alcohol (OR 1.21, 95%CI 1.05–1.39) were associated with an increased asthma risk. CONCLUSIONS: There are wide regional variations in the prevalence of asthma in India. With the exception of the findings for BMI, however, most of the associations of asthma with the risk factors are relatively weak and account for only a small proportion of cases. RÉSUMÉ CONTEXTE ET MÉTHODES: Nous avons estimé la prévalence auto-rapportée de l’asthme chez les Indiens adultes et examiné plusieurs facteurs de risque influençant la prévalence de la maladie. L’analyse repose sur 99 574 femmes et 56 742 hommes âgés de 20 à 49 ans et inclus dans la troisième Enquête Nationale des Familles en Inde, 2005–2006. On a utilisé l’analyse de régression logistique multiple pour estimer les odds ratio de prévalence pour l’asthme, après ajustement pour divers facteurs de risque. RÉSULTATS: La prévalence auto-rapportée de l’asthme est de 1,8% (IC95% 1,6–2,0) parmi les hommes et de 1,9% (IC95% 1,8–2,0) parmi les femmes, les taux étant plus élevés dans les zones rurales que dans les zones urbaines, et les différences géographiques étant marquées. Après ajustement pour les facteurs de risque d’asthme connus, les femmes sont 1,2 fois plus susceptibles de souffrir de l’asthme que les hommes. La consommation quotidienne ou hebdomadaire de lait/produits laitiers, de légumes à feuilles vertes et de fruits est en association avec un risque plus faible d’asthme alors que la consommation de poulet ou de viande, un index de masse corporelle (BMI) plus bas (<16 kg/m2, OR 2,08 ; IC95% 1,73–2,50) ainsi qu’un BMI plus élevé (>30 kg/m2, OR 1,67 ; IC95% 1,36–2,06), le fait de fumer du tabac actuellement (OR 1,30 ; IC95% 1,12–1,50) et l’utilisation de l’alcool à un moment quelconque (OR 1,21 ; IC95% 1,05–1,39) sont en association avec un risque accru d’asthme. La prévalence de l’asthme en Inde varie largement selon les régions. Toutefois, à l’exception des observations sur le BMI, l’association de l’asthme avec les facteurs de risque est relativement faible et ne rend compte que d’une petite proportion des cas seulement. RESUMEN MARCO DE REFERENCIA Y MÉTODOS: Se calculó la prevalencia de asma autorreferida en los adultos en la India y se evaluaron varios factores de riesgo que influyen sobre la prevalencia de la enfermedad. El estudio se basó en las 99 574 mujeres y los 56 742 hombres de 20 a 49 años de edad que participaron en la tercera Encuesta Nacional sobre la Salud de la Familia en la India entre el 2005 y el 2006. Mediante un análisis de regresión logística multifactorial se calculó la prevalencia de asma y el cociente de posibilidades de padecerla, al corregir diversos factores de riesgo. RESULTADOS: La prevalencia de asma autorreferida fue 1,8% en los hombres (intervalo de confianza [IC] del 95% 1,6 a 2,0) y 1,9% en las mujeres (IC95% 1,8 a 2,0); se observaron tasas más altas en las zonas rurales que en las zonas urbanas y se presentaron diferencias geográficas considerables. Tras corregir en función de algunos factores de riesgo de padecer asma conocidos, las mujeres presentaron una probabilidad 1,2 veces superior a los hombres de sufrir la enfermedad. El consumo diario o semanal de leche o productos lácteos, hortalizas de hojas verdes y frutas se asoció con un menor riesgo de asma y el consumo de carne de pollo o de res, un bajo índice de masa corporal (<16 kg/m2; OR 2,08; IC95% 1,73 a 2,50) igual que un alto índice de masa corporal (>30 kg/m2; OR 1,67; IC95% 1,36 a 2,06), el tabaquismo actual (OR 1,30; IC95% 1,12 a 1,50) y el consumo de alcohol en algún momento de la vida (OR 1,21; IC95% 1,05 a 1,39) se asociaron con un mayor riesgo de padecer la enfermedad. CONCLUSIÓN: Existen amplias variaciones geográficas en la prevalencia de asma en la India. Sin embargo, con la excepción del índice de masa corporal, la mayor parte de las asociaciones del asma con los factores de riesgo fueron débiles y explican solo una pequeña proporción de los casos.","title":"Prevalence and risk factors for self-reported asthma in an adult Indian population: a cross-sectional survey"},{"docid":"MED-3283","text":"Available information indicates that long-lived mammals have low rates of reactive oxygen species (ROS) generation and oxidative damage at their mitochondria. On the other hand, many studies have consistently shown that dietary restriction (DR) in rodents also decreases mitochondrial ROS (mtROS) production and oxidative damage to mitochondrial DNA and proteins. It has been observed that protein restriction also decreases mtROS generation and oxidative stress in rat liver, whereas neither carbohydrate nor lipid restriction change these parameters. This is interesting because protein restriction also increases maximum longevity in rodents (although to a lower extent than DR) and is a much more practicable intervention for humans than DR, whereas neither carbohydrate nor lipid restriction seem to change rodent longevity. Moreover, it has been found that isocaloric methionine restriction also decreases mtROS generation and oxidative stress in rodent tissues, and this manipulation also increases maximum longevity in rats and mice. In addition, excessive dietary methionine also increases mtROS generation in rat liver. These studies suggest that the reduced intake of dietary methionine can be responsible for the decrease in mitochondrial ROS generation and the ensuing oxidative damage that occurs during DR, as well as for part of the increase in maximum longevity induced by this dietary manipulation. In addition, the mean intake of proteins (and thus methionine) of Western human populations is much higher than needed. Therefore, decreasing such levels to the recommended ones has a great potential to lower tissue oxidative stress and to increase healthy life span in humans while avoiding the possible undesirable effects of DR diets.","title":"Lowered methionine ingestion as responsible for the decrease in rodent mitochondrial oxidative stress in protein and dietary restriction possible i..."},{"docid":"MED-1250","text":"The effect of plant and animal protein on blood lipid levels was investigated in eight healthy normolipidemic men aged 18 to 27 yr. All subjects were fed both plant and animal protein diets in a cross-over design. Each diet was consumed for a 21-day period. Proteins from commonly used plant sources made up the plant protein diet. Beef protein was substituted for 55% of the plant proteins in the animal protein diet. Fasting venous blood samples were collected at the beginning of the study and at 7-day intervals throughout the 42-day study. Serum was analyzed for total cholesterol and triglycerides. Plasma low-density and high-density lipoprotein cholesterol were determined. There were not any statistically significant differences in mean serum total cholesterol or mean plasma low-density lipoprotein cholesterol when subjects consumed the diets. Mean plasma high-density lipoprotein cholesterol levels were significantly (p less than 0.05) elevated at the end of the 21-day period when the animal protein diet was consumed (48 +/- 3 mg/dl) compared to the period when the plant protein diet was fed (42 +/- 2 mg/dl). Mean serum triglyceride values were significantly (p less than 0.05) increased at day 7 of the plant protein diet period (136 +/- 19 mg/dl) compared to the same time period when the animal protein diet was consumed (84 +/- 12 mg/dl). The results of the study indicated that the ingestion of a diet in which 55% of the protein was supplied by beef protein was not associated with a hypercholesterolemic effect in healthy normolipidemic young men.","title":"A comparison of the effect of diets containing beef protein and plant proteins on blood lipids of healthy young men."},{"docid":"MED-1229","text":"Milk has been recognized to represent a functionally active nutrient system promoting neonatal growth of mammals. Cell growth is regulated by the nutrient-sensitive kinase mechanistic target of rapamycin complex 1 (mTORC1). There is still a lack of information on the mechanisms of mTORC1 up-regulation by milk consumption. This review presents milk as a materno-neonatal relay system functioning by transfer of preferential amino acids, which increase plasma levels of glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), insulin, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) for mTORC1 activation. Importantly, milk exosomes, which regularly contain microRNA-21, most likely represent a genetic transfection system enhancing mTORC1-driven metabolic processes. Whereas human breast milk is the ideal food for infants allowing appropriate postnatal growth and species-specific metabolic programming, persistent high milk signaling during adolescence and adulthood by continued cow´s milk consumption may promote mTORC1-driven diseases of civilization.","title":"Milk is not just food but most likely a genetic transfection system activating mTORC1 signaling for postnatal growth"},{"docid":"MED-2472","text":"Thirty-five patients who had suffered from bronchial asthma for an average of 12 yr, all receiving long-term medication, 20 including cortisone, were subject to therapy with vegan food for 1 yr. In almost all cases, medication was withdrawn or drastically reduced. There was a significant decrease in asthma symptoms. Twenty-four patients (69%) fulfilled the treatment. Of these, 71% reported improvement at 4 months and 92% at 1 yr. There was a significant improvement in a number of clinical variables; for example, vital capacity, forced expiratory volume at one sec and physical working capacity, as well as a significant change in various biochemical indices as haptoglobin, IgM, IgE, cholesterol, and triglycerides in blood. Selected patients, with a fear of side-effects of medication, who are interested in alternative health care, might get well and replace conventional medication with this regimen.","title":"Vegan regimen with reduced medication in the treatment of bronchial asthma."},{"docid":"MED-3311","text":"OBJECTIVES: We studied mortality in two separate cohorts of workers in abattoirs (N=4996) and meat processing plants (N=3642) belonging to a meatcutters' union, because they were exposed to viruses that cause cancer in food animals, and also to chemical carcinogens at work. METHODS: Standardized mortality ratios (SMRs) and proportional mortality ratios (PMRs) were estimated for each cohort as a whole and in subgroups defined by race and sex, using the US general population mortality rates for comparison. Study subjects were followed up from January 1950 to December 2006, during which time over 60% of them died. RESULTS: An excess of deaths from cancers of the base of the tongue, esophagus, lung, skin, bone and bladder, lymphoid leukemia, and benign tumors of the thyroid and other endocrine glands, and possibly Hodgkin's disease, was observed in abattoir and meat processing workers. Significantly lower SMRs were recorded for cancer of the thymus, mediastinum, pleura, etc., breast cancer, and non-Hodgkin's lymphoma. CONCLUSION: This study confirms the excess occurrence of cancer in workers in abattoirs and meat processing plants, butchers, and meatcutters, previously reported in this cohort and other similar cohorts worldwide. Large nested case-control studies are now needed to examine which specific occupational and non-occupational exposures are responsible for the excess. There is now sufficient evidence for steps to be taken to protect workers from carcinogenic exposures at the workplace. There are also serious implications for the general population which may also be exposed to some of these viruses. Copyright © 2011 Elsevier Ltd. All rights reserved.","title":"Cancer mortality in workers employed in cattle, pigs, and sheep slaughtering and processing plants."},{"docid":"MED-2357","text":"Patients with cancer have circulating heterophile antibodies that agglutinate animal red cells via recognition of the mammalian cell surface sialic acid N-glycolylneuraminic acid (Neu5Gc), which was long considered an oncofetal antigen in humans. However, humans are genetically deficient in Neu5Gc production and instead metabolically accumulate Neu5Gc from dietary sources, particularly red meats and milk products. Moreover, mice with a human-like defect showed no alternate pathway for Neu5Gc synthesis and even normal humans express anti-Neu5Gc antibodies. We show here that human tumors accumulate Neu5Gc that is covalently attached to multiple classes of glycans. The paradox of human tumor Neu5Gc accumulation in the face of circulating anti-Neu5Gc antibodies was hypothesized to be due to facilitation of tumor progression by the resulting low-grade chronic inflammation. Indeed, murine tumors expressing human-like levels of Neu5Gc show accelerated growth in syngeneic mice with a human-like Neu5Gc deficiency, coincident with the induction of anti-Neu5Gc antibodies and increased infiltration of inflammatory cells. Transfer of polyclonal monospecific syngeneic mouse anti-Neu5Gc serum also enhanced growth of transplanted syngeneic tumors bearing human-like levels of Neu5Gc, with tumors showing evidence for antibody deposition, enhanced angiogenesis and chronic inflammation. These effects were suppressed by a cyclooxygenase-2 inhibitor, a drug type known to reduce human carcinoma risk. Finally, affinity-purified human anti-Neu5Gc antibodies also accelerate growth of Neu5Gc-containing tumors in Neu5Gc-deficient mice. Taken together, the data suggest that the human propensity to develop diet-related carcinomas is contributed to by local chronic inflammation, resulting from interaction of metabolically-accumulated dietary Neu5Gc with circulating anti-Neu5Gc antibodies.","title":"Evidence for a human-specific mechanism for diet and antibody-mediated inflammation in carcinoma progression"},{"docid":"MED-3282","text":"BACKGROUND AND AIMS: The mechanisms of cancer cell growth and metastasis are still not entirely understood, especially from the viewpoint of chemical reactions in tumours. Glycolytic metabolism is markedly accelerated in cancer cells, causing the accumulation of glucose (a reducing sugar) and methionine (an amino acid), which can non-enzymatically react and form carcinogenic substances. There is speculation that this reaction produces gaseous sulfur-containing compounds in tumour tissue. The aims of this study were to clarify the products in tumour and to investigate their effect on tumour proliferation. METHODS: Products formed in the reaction between glucose and methionine or its metabolites were analysed in vitro using gas chromatography. Flatus samples from patients with colon cancer and exhaled air samples from patients with lung cancer were analysed using near-edge x-ray fine adsorption structure spectroscopy and compared with those from healthy individuals. The tumour proliferation rates of mice into which HT29 human colon cancer cells had been implanted were compared with those of mice in which the cancer cells were surrounded by sodium hyaluronate gel to prevent diffusion of gaseous material into the healthy cells. RESULTS: Gaseous sulfur-containing compounds such as methanethiol and hydrogen sulfide were produced when glucose was allowed to react with methionine or its metabolites homocysteine or cysteine. Near-edge x-ray fine adsorption structure spectroscopy showed that the concentrations of sulfur-containing compounds in the samples of flatus from patients with colon cancer and in the samples of exhaled air from patients with lung cancer were significantly higher than in those from healthy individuals. Animal experiments showed that preventing the diffusion of sulfur-containing compounds had a pronounced antitumour effect. CONCLUSIONS: Gaseous sulfur-containing compounds are the main products in tumours and preventing the diffusion of these compounds reduces the tumour proliferation rate, which suggests the possibility of a new approach to cancer treatment.","title":"Generation of gaseous sulfur-containing compounds in tumour tissue and suppression of gas diffusion as an antitumour treatment."},{"docid":"MED-3356","text":"OBJECTIVE: This study examined changes in desires to eat high-fat and low-fat foods across an obesity treatment program. The hypotheses under examination were (1) preferences for low-fat foods would increase across time and (2) preferences for high-fat foods would decrease across time. DESIGN: Single-group, prospective examination of desires to eat 48 foods, categorized according to fat content, before and after the 16-week treatment program. SETTING: University clinic, Memphis, Tennessee. PARTICIPANTS: 118 obese (mean weight = 194.4 lbs) women (mean age = 45.24 years) participating in an obesity treatment program. INTERVENTION: A 16-week cognitive-behavioral program for obesity. VARIABLES MEASURED: Desires to eat 48 foods varying in fat content and whether or not participants actually ate these foods. ANALYSIS: Analysis of variance, multiple regression, and paired t tests. RESULTS: The results indicate that during the program, preferences for low-fat foods increased, whereas preferences for high-fat foods decreased. These changes mirrored the changes in consumption of both low-fat and high-fat foods. CONCLUSIONS AND IMPLICATIONS: Within a behavioral economic perspective, the reinforcement value of low-fat foods may increase following a low-fat dietary intervention, whereas the reinforcing properties of high-fat foods may decline. This is desirable as low-fat foods hold many advantages over high-fat foods in terms of weight maintenance.","title":"Desire to eat high- and low-fat foods following a low-fat dietary intervention."},{"docid":"MED-2512","text":"Ageing is a challenge for any living organism and human longevity is a complex phenotype. With increasing life expectancy, maintaining long-term health, functionality and well-being during ageing has become an essential goal. To increase our understanding of how ageing works, it may be advantageous to analyze the phenotype of centenarians, perhaps one of the best examples of successful ageing. Healthy ageing involves the interaction between genes, the environment, and lifestyle factors, particularly diet. Besides evaluating specific gene-environment interactions in relation to exceptional longevity, it is important to focus attention on modifiable lifestyle factors such as diet and nutrition to achieve extension of health span. Furthermore, a better understanding of human longevity may assist in the design of strategies to extend the duration of optimal human health. In this article we briefly discuss relevant topics on ageing and longevity with particular focus on dietary patterns of centenarians and nutrient-sensing pathways that have a pivotal role in the regulation of life span. Finally, we also discuss the potential role of Nrf2 system in the pro-ageing signaling emphasizing its phytohormetic activation.","title":"Extending healthy ageing: nutrient sensitive pathway and centenarian population"},{"docid":"MED-3931","text":"Although a plant-based diet can provide some benefits in Parkinson's disease (PD), no study to date has evaluated the effectiveness of a plant-food diet in the management of the disease. In this pilot study, we compared the effect of a plant-food menu (PFD) and of a omnivorous menu on motor performance of 25 PD patients, 12 in the intervention group (PDi) and 13 in the control group (PDc). After 4 weeks, the PDi group showed a significant reduction (Mann-Whitney test) in the Unified Parkinson's Disease Rating Scale, total score (47.67 vs. 74.46, P = 0.008) and sub-score III motor performances (25.42 vs. 46.46, P = 0.001), and the modified Hoehn and Yahr Staging Scale (1.96 vs. 3.15, P = 0.005). These data suggest that PFD may be useful in the management of PD patients by improving their motor performances. Additional studies are needed in order to confirm these preliminary results.","title":"Pilot dietary study with normoproteic protein-redistributed plant-food diet and motor performance in patients with Parkinson's disease."},{"docid":"MED-4433","text":"BACKGROUND: The role of zoonotic biological agents in human cancer occurrence has been little studied. Humans are commonly exposed to viruses that naturally infect and cause cancer in food animals such as poultry that constitute part of the biological environment. It is not known if these viruses cause cancer in humans. OBJECTIVE: To study cancer mortality in the largest cohort to date, of 20,132 workers in poultry slaughtering and processing plants, a group with the highest human exposures to these viruses. METHODS: Mortality in poultry workers was compared with that in the US general population through the estimation of standardized mortality ratios. RESULTS: Significantly increased risks were observed in the cohort as a whole or in subgroups, for several cancer sites, viz: cancers of the buccal cavity and pharynx; pancreas; trachea/bronchus/lung; brain; cervix; lymphoid leukemia; monocytic leukemia; and tumors of the hemopoietic and lymphatic systems. Elevated SMRs that were not statistically significant were observed for cancers of the liver, nasopharynx, myelofibrosis, and myeloma. New sites observed to be significantly in excess in this study were cancers of the cervix and penis. CONCLUSION: This large study provides evidence that a human group with high exposure to poultry oncogenic viruses has increased risk of dying from several cancers. Other occupational carcinogenic exposures could be of importance in explaining some of the findings, such as fumes from wrapping machines. These findings may have implications for public health amongst persons in the general population who may also be exposed to these viruses. What is needed now are epidemiologic studies that can demonstrate whether the excess of specific cancers can be attributed to specific occupational exposures while adequately controlling for other potential occupational and non-occupational carcinogenic exposures. Copyright 2010 Elsevier Inc. All rights reserved.","title":"Cancer mortality in poultry slaughtering/processing plant workers belonging to a union pension fund."},{"docid":"MED-2474","text":"This ISAAC Phase Three synthesis provides summarised information on the main findings of the study, regional tables and figures related to the prevalence and severity of current symptoms of asthma, rhinoconjunctivitis and eczema in the main regions of the world. The large number of surveyed children (≈1,200,000), the large number of centres (233) and countries (98) that participated in ISAAC Phase Three makes this study the most comprehensive survey of these diseases ever undertaken. Globally, the prevalence for current asthma, rhinoconjunctivitis and eczema in the 13-14-year age group was 14.1%, 14.6% and 7.3%, respectively. In the 6-7-year age group the prevalence for current asthma, rhinoconjunctivitis and eczema was 11.7%, 8.5% and 7.9%, respectively. The study shows a wide variability in the prevalence and severity of asthma, rhinoconjunctivitis and eczema which occurs not just between regions and countries but between centres in the same country and centres in the same city. This study definitively establishes that the prevalence of those diseases can be very high in non-affluent centres with low socioeconomic conditions. The large variability also suggests a crucial role of local environment characteristics to determine the differences in prevalence between one place and another. Thus, ISAAC Phase Three has provided a large body of epidemiological information on asthma, rhinoconjunctivitis and eczema in childhood from contrasting environments which is expected to yield new clues about the aetiology of those conditions and reasons for their marked global variability. Copyright © 2012 SEICAP. Published by Elsevier Espana. All rights reserved.","title":"The International Study of Asthma and Allergies in Childhood (ISAAC) Phase Three: a global synthesis."},{"docid":"MED-2823","text":"Curcumin, the yellow pigment from the rhizoma of Curcuma longa, is a widely studied phytochemical which has a variety of biological activities: anti-inflammatory and anti-oxidative. In this review we discuss the biological mechanisms and possible clinical effects of curcumin treatment on cancer therapy, and neurodegenerative diseases such as Alzheimer's Disease, with particular attention to the cell death processes induced by curcumin. Since oxidative stress and inflammation are major determinants of the aging process, we also argue that curcumin can have a more general effect that slows down the rate of aging. Finally, the effects of curcumin can be described as xenohormetic, since it activates a sort of stress response in mammalian cells.","title":"Curcumin in Cell Death Processes: A Challenge for CAM of Age-Related Pathologies"},{"docid":"MED-3295","text":"Background Few studies have investigated mortality in seafood workers worldwide, and no such study has been conducted in the United States. The objective of this study was to investigate mortality in American seafood workers. Methods The study population was derived from 4 states and consisted of 4116 subjects who worked mainly in seafood processing plants. They were followed up from 1966 to 2003. Standardized mortality ratios (SMRs) and proportional mortality ratios (PMRs) were estimated, using the US general population for comparison. Results About 45% of the cohort was born after 1949. A total of 788 deaths were recorded; 53% of the decedents were female, and 88% were white. The SMRs for stomach cancer and disorders of the thyroid gland in the cohort as a whole were 2.1 (95% confidence interval [CI], 1.1–3.8) and 6.1 (95% CI 1.3–18.0), respectively. The SMRs for breast cancer, and occlusion/stenosis of the pre-cerebral/cerebral arteries in the cohort as a whole were 0.5 (95% CI, 0.3–0.9) and 0.5 (95% CI, 0.2–0.8), respectively. The SMR for ischemic heart disease in white females was 0.8 (95% CI, 0.6–0.9). Conclusions This cohort had excess deaths from stomach cancer and disorders of the thyroid gland, and deficit of deaths from breast cancer, stroke and ischemic heart disease. The significance of these findings is unknown, especially as less than 20% of the cohort were deceased. Nevertheless, the cohort is unique and important, and further follow-up may shed more light on mortality patterns in this occupational group.","title":"Cancer and Noncancer Mortality Among American Seafood Workers"},{"docid":"MED-3321","text":"Avian leukosis/sarcoma viruses (ALSV) infect and cause cancers in chickens. Poultry workers are exposed to ALSV and other infectious agents in the workplace. This study examines if industrial hygiene assessment of antibody levels in poultry workers can identify risky job tasks at the higher exposure risk to an infectious agent, i.e., ALSV. We compared ALSV antibody levels in poultry workers and control subjects. Occupational and demographical factors were examined for an association with the exposure risk in poultry workers. We found that the antibody levels were significantly higher in poultry workers than in control subjects. Job category and age together were significantly associated with the antibody levels in workers. Certain job tasks were identified with significantly higher antibody levels as compared to others, implying that recommendations should be made to protect workers at these jobs. The findings of this study indicate that the measurement of antibody levels in workers can be useful for industrial hygiene assessment of exposure to infectious agents.","title":"Occupational exposure assessment using antibody levels: exposure to avian leukosis/sarcoma viruses in the poultry industry."},{"docid":"MED-3232","text":"High dietary acid load (DAL) may be detrimental to bone mineral density (BMD). The objectives of the study were to: 1) evaluate the cross-sectional relation between DAL and BMD; 2) determine whether calcium intake modifies this association. Men (n=1218) and women (n=907) ≥60y were included from the National Health and Nutrition Examination Survey 2005–2008. Nutrient intake from 2–24h recalls was used to calculate net endogenous acid production (NEAP) and potential renal acid load (PRAL) (mEq/d). PRAL was calculated from dietary calcium (PRALdiet) and diet + supplemental calcium (PRALtotal). Tests for linear trend in adjusted mean BMD of the hip and lumbar spine were performed across energy adjusted NEAP and PRAL quartiles. Modification by calcium intake (dietary or total) above or below 800 mg/d was assessed by interaction terms. Overall, mean age was 69 ± 0.3y. Among women, there was no association between NEAP and BMD. PRALdiet was positively associated with proximal femur BMD (p trend=0.04). No associations were observed with PRALtotal at any BMD site (P-range: 0.38–0.82). Among men, no significant associations were observed of BMD with NEAP or PRAL. However, an interaction between PRALdiet and calcium intake was observed with proximal femur BMD (p=0.08). An inverse association between PRALdiet and proximal femur BMD was detected among men <800 mg/d dietary calcium (p=0.02); and no associations ≥800 mg/d (p=0.98). A significant interaction with PRALtotal was not observed. In conclusion, when supplemental calcium is considered, there is no association between DAL and BMD among adults. Men with low dietary calcium showed an inverse relation with PRAL at the proximal femur; in women no interaction was observed. This study highlights the importance of calcium intakes in counteracting the adverse effect of DAL on bone health. Further research should determine the relation between DAL and change in BMD with very low calcium intake.","title":"Dietary acid load is associated with lower bone mineral density in men with low intake of dietary calcium"},{"docid":"MED-4198","text":"In this study, silkworm moth (Bombyx mori L.) larvae were regarded as an animal protein source for astronauts in the bioregenerative life support system during long-term deep space exploration in the future. They were fed with mulberry and stem lettuce leaves during the first three instars and the last two instars, respectively. In addition, this kind of environmental approach, which utilised inedible biomass of plants to produce animal protein of high quality, can likewise be applied terrestrially to provide food for people living in extreme environments and/or impoverished agro-ecosystems, such as in polar regions, isolated military bases, ships, submarines, etc. Respiration characteristics of the larvae during development under two main physiological conditions, namely eating and not-eating of leaves, were studied. Nutrient compositions of silkworm powder (SP), ground and freeze-dried silkworms on the 3rd day of the 5th instar larvae, including protein, fat, vitamins, minerals and fatty acids, were measured using international standard methods. Silkworms' respiration rates, measured when larvae were eating mulberry leaves, were higher than those of similar larvae that hadn't eaten such leaves. There was a significant difference between silkworms fed on mulberry leaves and those fed on stem lettuce in the 4th and 5th instars (P<0.01). Amounts of CO2 exhaled by the silkworms under the two physiological regimes differed from each other (P<0.01). There was also a significant difference between the amount of O2 inhaled when the insects were under the two physiological statuses (P<0.01). Moreover, silkworms' respiration quotient under the eating regime was larger than when under the not-eating regime. The SP was found to be rich in protein and amino acids in total; 12 essential vitamins, nine minerals and twelve fatty acids were detected. Moreover, 359 kcal could be generated per 100 gram of SP (dry weight).","title":"Insect food for astronauts: gas exchange in silkworms fed on mulberry and lettuce and the nutritional value of these insects for human consumption ..."},{"docid":"MED-2446","text":"BACKGROUND: Allergic diseases have risen in prevalence over recent decades. The aetiology remains unclear but is likely to be a result of changing lifestyle and/or environment. A reduction in antioxidant intake, consequent to reduced intake of fresh fruits and vegetables, has been suggested as a possible cause. OBJECTIVE: To investigate whether dietary antioxidant intake at age 5 was related to atopy at 5 and 8 years of age amongst children in an unselected birth cohort. METHODS: Children were followed from birth. Parents completed a validated respiratory questionnaire and children were skin prick tested at 5 and 8 years of age. Serum IgE levels were measured at age 5. At age 5, antioxidant intake was assessed using a semi-quantitative food frequency questionnaire (FFQ). A nutrient analysis program computed nutrient intake, and frequency counts of foods high in the antioxidant vitamins A, C and E were assessed. RESULTS: Eight hundred and sixty-one children completed both the respiratory and FFQ. Beta-carotene intake was associated with reduced risk of allergic sensitization at age 5 [0.80 (0.68-0.93)] and 8 [0.81 (0.70-0.94)]. In addition, beta-carotene intake was negatively associated with total IgE levels (P = 0.002). Vitamin E intake was associated with an increased risk of allergic sensitization [1.19 (1.02-1.39)], only at age 5. There was no association between antioxidant intakes and wheeze or eczema. CONCLUSION: Increased beta-carotene intake was associated with a reduced risk of allergic sensitization and lower IgE levels, in 5- and 8-year-old children. Dietary antioxidants may play a role in the development of allergic sensitization.","title":"Dietary antioxidant intake, allergic sensitization and allergic diseases in young children."},{"docid":"MED-2201","text":"Measuring food prices per gram, rather than per calorie, is one way to make healthful vegetables appear less expensive. However, a better measure of affordability would take the nutrient content of vegetables into account. This study, based on analyses of US Department of Agriculture datasets, aimed to identify which vegetables, including juices and soups, provided the most nutrients per unit cost. Nutrient density was measured using the Nutrient Rich Foods (NRF) index, based on nine nutrients to encourage: protein; fiber; vitamins A, C, and E; calcium; iron; magnesium; and potassium; and on three nutrients to limit: saturated fat, added sugar, and sodium. Food cost in dollars was calculated per 100 g, per 100 kcal, per serving, and per nutrient content. One-way analyses of variance with post hoc tests were used to determine statistical significance. Results showed that tomato juices and tomato soups, dark green leafy and nonleafy vegetables, and deep yellow vegetables, including sweet potatoes, had the highest NRF scores overall. Highest NRF scores per dollar were obtained for sweet potatoes, white potatoes, tomato juices and tomato soups, carrots, and broccoli. Tomato sauces, raw tomatoes, and potato chips were eaten more frequently than were many other vegetables that were both more affordable and more nutrient-rich. These new measures of affordable nutrition can help foodservice and health professionals identify those vegetables that provide the highest nutrient density per unit cost. Processed vegetables, including soups and juices, can contribute to the quality and the affordability of the diet. Copyright © 2013 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.","title":"New metrics of affordable nutrition: which vegetables provide most nutrients for least cost?"},{"docid":"MED-3306","text":"OBJECTIVES: Occupation as a farmer has been associated with increased risks of haematological cancers in adults. This study aimed to examine whether farm exposures in childhood contribute to these risks, by using parental occupation in farming as a proxy for growing up on a farm. METHODS: New Zealand death records (1998-2003) of persons aged 35-85 were extracted (n=114 289). For 82.3% usual occupation and the occupation of at least one of the parents could be coded (n=94 054). Unconditional logistic regression analyses included 3119 haematological cancer deaths (cases) and 90 935 deaths from other causes (controls). ORs for farming and growing up on a farm were adjusted for each other, year of birth, age at death, socio-economic status, Māori ethnicity, immigration status and sex. RESULTS: Growing up on a livestock farm was positively associated with haematological cancer (OR 1.22, 95% CI 1.05 to 1.41), particularly for poultry farms (OR 2.99, 95% CI 1.44 to 6.21), while growing up on a crop farm was not (OR 0.81, 95% CI 0.64 to 1.03). Crop farming in adulthood was associated with an increased haematological cancer risk (OR 1.49, 95% CI 1.13 to 1.96), while livestock farming was not (OR 0.80, 95% CI 0.63 to 1.00), except for beef cattle farming (OR 2.99, 95% CI 1.28 to 7.00). These results did not change appreciably when different control groups with different causes of death were used. CONCLUSIONS: These results could suggest a role for early life biological exposures in the development of haematological cancers.","title":"Farming, growing up on a farm, and haematological cancer mortality."},{"docid":"MED-3231","text":"This review looks at the role of an alkaline diet in health. Pubmed was searched looking for articles on pH, potential renal acid loads, bone health, muscle, growth hormone, back pain, vitamin D and chemotherapy. Many books written in the lay literature on the alkaline diet were also reviewed and evaluated in light of the published medical literature. There may be some value in considering an alkaline diet in reducing morbidity and mortality from chronic diseases and further studies are warranted in this area of medicine.","title":"The Alkaline Diet: Is There Evidence That an Alkaline pH Diet Benefits Health?"},{"docid":"MED-3452","text":"Vitamins have traditionally been considered as food components that are required in the normal diet to prevent deficiencies. However, a newer concept of the function of vitamins in nutrition has taken them beyond simply prevention of deficiency symptoms. This concept considers that many vitamins, when taken in relatively large doses, have important functions beyond preventing deficiencies. Linus Pauling was instrumental in putting forward this concept, particularly for vitamin C. Thus, relatively high intakes of vitamins, and in particular vitamins C and E which are antioxidants, are considered to be healthy for the human population. This may be true in some special situations such as, for instance, the prevention of Alzheimer's disease progression. However, recent epidemiological evidence has not supported the claim that antioxidant vitamins increase well-being and prolong life span. In fact, vitamin supplementation may be even detrimental and reduce life span. A new concept that we would like to put forward is that nutrients up-regulate the endogenous antioxidant defences. This is particularly true in the case of phytoestrogens for example, which bind to oestrogen receptors and eventually up-regulate the expression of antioxidant genes. In this review we discuss the pros and cons of antioxidant vitamin supplementation and also the possibility that the ingestion of some nutrients may be very effective in increasing antioxidant defences by up-regulating the activity of antioxidant enzymes which are normally present in the cell.","title":"Fostering antioxidant defences: up-regulation of antioxidant genes or antioxidant supplementation?"},{"docid":"MED-4950","text":"Previously used standards for the diagnosis of precocious puberty in girls no longer appear to be appropriate in the USA, in that a significant number of girls are being seen in paediatricians' offices with breast budding before 8 years of age. The timing of menarche, however, has changed little over the past few decades. Early maturing girls are more likely to become obese in adolescence and adulthood than normal or late maturing girls. Early maturing white girls are heavier at the onset of puberty, but this is not the case for African-American girls or boys of either race. Boys and girls with premature pubarche may be more hyperinsulinaemic than normal children, and girls with premature pubarche more likely to develop functional ovarian and adrenal hyperandrogenism. Early menarche is preceded by prepubertal hyperinsulinaemia. It is proposed that pubertal onset, although not necessarily the tempo of puberty, is influenced by hyperinsulinaemia and insulin resistance. If this hypothesis is correct, insulin resistance may be more prevalent in US children than previously recognized. An advance in timing of onset of puberty has not been noted in other countries, although it is likely that this phenomenon may become more prevalent as other countries adopt a more American lifestyle and diet.","title":"The pubertal timing controversy in the USA, and a review of possible causative factors for the advance in timing of onset of puberty."},{"docid":"MED-2501","text":"Amino acids play fundamental roles in the cell both as the building blocks of new proteins and as metabolic precursors. To adapt to their limitation during periods of protein starvation, multiple adaptive mechanisms have evolved, including a rapid cessation of new protein synthesis, an increase in amino acid biosynthesis and transport, and autophagy. Here, we discuss what we currently know about how amino acid limitation is sensed, and how this sensing might be transmitted to mTORC1 to regulate protein synthesis and autophagy. Copyright © 2012 Elsevier Ltd. All rights reserved.","title":"Amino acid sensing and regulation of mTORC1."},{"docid":"MED-1097","text":"Moses Maimonides (1135-1204), physician and philosopher, was the greatest Jewish thinker of the Middle Ages. Faced with a life of persecution, exile, and tragedy, Maimonides overcame obstacles to become the leading physician in his era, a clinician whose skills were sought across continents. Despite long days caring for patients, Maimonides wrote extensively about both medicine and philosophy. His medical works span all topics of clinical medicine and reflect rational thinking and an understanding of the relationship between mind and body. Well known for his philosophical writings, such as The Guide for the Perplexed, Maimonides codified Jewish law and revolutionized Jewish thinking. This review of his life and achievements provides insight into the world of a remarkable 12th-century physician and may offer valuable lessons for physicians today.","title":"Moses Maimonides: medieval physician and scholar."},{"docid":"MED-4722","text":"BACKGROUND: There has been a resurgence of interest in the controversial relation between dietary protein and bone health. OBJECTIVE: This article reports on the first systematic review and meta-analysis of the relation between protein and bone health in healthy human adults. DESIGN: The MEDLINE (January 1966 to September 2007) and EMBASE (1974 to July 2008) databases were electronically searched for all relevant studies of healthy adults; studies of calcium excretion or calcium balance were excluded. RESULTS: In cross-sectional surveys, all pooled r values for the relation between protein intake and bone mineral density (BMD) or bone mineral content at the main clinically relevant sites were significant and positive; protein intake explained 1-2% of BMD. A meta-analysis of randomized placebo-controlled trials indicated a significant positive influence of all protein supplementation on lumbar spine BMD but showed no association with relative risk of hip fractures. No significant effects were identified for soy protein or milk basic protein on lumbar spine BMD. CONCLUSIONS: A small positive effect of protein supplementation on lumbar spine BMD in randomized placebo-controlled trials supports the positive association between protein intake and bone health found in cross-sectional surveys. However, these results were not supported by cohort study findings for hip fracture risk. Any effects found were small and had 95% CIs that were close to zero. Therefore, there is a small benefit of protein on bone health, but the benefit may not necessarily translate into reduced fracture risk in the long term.","title":"Dietary protein and bone health: a systematic review and meta-analysis."},{"docid":"MED-3272","text":"Objective Early detection and early treatment are of vital importance to the successful treatment of various cancers. The development of a novel screening method that is as economical and non-invasive as the faecal occult blood test (FOBT) for early detection of colorectal cancer (CRC) is needed. A study was undertaken using canine scent detection to determine whether odour material can become an effective tool in CRC screening. Design Exhaled breath and watery stool samples were obtained from patients with CRC and from healthy controls prior to colonoscopy. Each test group consisted of one sample from a patient with CRC and four control samples from volunteers without cancer. These five samples were randomly and separately placed into five boxes. A Labrador retriever specially trained in scent detection of cancer and a handler cooperated in the tests. The dog first smelled a standard breath sample from a patient with CRC, then smelled each sample station and sat down in front of the station in which a cancer scent was detected. Results 33 and 37 groups of breath and watery stool samples, respectively, were tested. Among patients with CRC and controls, the sensitivity of canine scent detection of breath samples compared with conventional diagnosis by colonoscopy was 0.91 and the specificity was 0.99. The sensitivity of canine scent detection of stool samples was 0.97 and the specificity was 0.99. The accuracy of canine scent detection was high even for early cancer. Canine scent detection was not confounded by current smoking, benign colorectal disease or inflammatory disease. Conclusions This study shows that a specific cancer scent does indeed exist and that cancer-specific chemical compounds may be circulating throughout the body. These odour materials may become effective tools in CRC screening. In the future, studies designed to identify cancer-specific volatile organic compounds will be important for the development of new methods for early detection of CRC.","title":"Colorectal cancer screening with odour material by canine scent detection"},{"docid":"MED-4038","text":"We previously reported an association between prenatal exposure to airborne PAH and lower birth weight, birth length and head circumference. The main goal of the present analysis was to assess the possible impact of co-exposure to PAH-containing of barbecued meat consumed during pregnancy on birth outcomes. The birth cohort consisted of 432 pregnant women who gave birth at term (>36 weeks of gestation). Only non-smoking women with singleton pregnancies, 18-35 years of age, and who were free from chronic diseases such as diabetes and hypertension were included in the study. Detailed information on diet over pregnancy was collected through interviews and the measurement of exposure to airborne PAHs was carried out by personal air monitoring during the second trimester of pregnancy. The effect of barbecued meat consumption on birth outcomes (birthweight, length and head circumference at birth) was adjusted in multiple linear regression models for potential confounding factors such as prenatal exposure to airborne PAHs, child’s sex, gestational age, parity, size of mother (maternal prepregnancy weight, weight gain in pregnancy) and prenatal environmental tobacco smoke (ETS). The multivariable regression model showed a significant deficit in birthweight associated with barbecued meat consumption in pregnancy (coeff = −106.0 g; 95%CI: −293.3, −35.8); The effect of exposure to airborne PAHs was about the same magnitude order (coeff. = −164.6 g; 95%CI: −172.3, − 34.7). Combined effect of both sources of exposure amounted to birth weight deficit of 214.3 g (95%CI: −419.0, − 9.6). Regression models performed for birth length and head circumference showed similar trends but the estimated effects were of borderline significance level. As the intake of barbecued meat did not affect the duration of pregnancy, the reduced birthweight could not have been mediated by shortened gestation period. In conclusion, the study results provided epidemiologic evidence that prenatal PAH exposure from diet including grilled meat might be hazardous for fetal development.","title":"IMPACT OF BARBECUED MEAT CONSUMED IN PREGNANCY ON BIRTH OUTCOMES ACCOUNTING FOR PERSONAL PRENATAL EXPOSURE TO AIRBORNE POLYCYCLIC AROMATIC HYDROCARBONS. BIRTH COHORT STUDY IN POLAND"},{"docid":"MED-2589","text":"BACKGROUND: Determination of the effects of dietary modification and hyperlipidemic medications in the elderly (> sixty-five years of age) patient has not been significantly investigated to date despite knowledge that elevated cholesterol (TC) and triglyceride (TG) levels increase the risk of coronary artery disease (CAD). METHODS: Twenty-seven individuals were placed into one of three treatment groups and longitudinally followed up to examine the effects of diet and hyperlipidemic medications on TC and TG levels. Group 1 (n = 14) received neither dietary nor drug therapy. Group 2 (n = 9) received dietary counseling without concomitant hyperlipidemic medications. Subjects in group 3 (n = 4) underwent dietary instruction for six months and hyperlipidemic medication(s) for eighteen months. RESULTS: Subjects in group 1 demonstrated a statistical increase in TC (P < or = 0.001) during the study. Patients in groups 2 (P < or = 0.001) and 3 (P < or = 0.05) demonstrated statistical improvement in TC reduction during dietary counseling. The effect on TC was blunted in group 3 after dietary counseling was discontinued. Reductions in TG levels were significant (P < or = 0.001) only for patients in group 2. CONCLUSION: Elderly individuals were able to significantly reduce both TC and TG levels by dietary modification alone. Minimal improvement was seen with the addition of hyperlipidemic medications.","title":"Treating hyperlipidemia in the elderly."},{"docid":"MED-4211","text":"Circulating levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) have each been associated with premenopausal breast cancer risks. We analyzed data from a cross-sectional study of 261 premenopausal Japanese women aged 20-54 yr with adequate nutritional status to evaluate the relationships between concentrations of IGF-1 and IGFBP-3 in serum and dietary intakes of soy, fats and other nutrients. Diet was assessed by a semiquantitative food frequency questionnaire. There was no significant correlation between soy product as well as soy isoflavone intake and serum IGF-1 or IGFBP-3 levels after controlling for age, total energy, percent body fat, and education level. Total fat intake was significantly inversely correlated with serum IGFBP-3 level (r = -0.13, P = 0.04). The correlations of saturated and monounsaturated fats with serum IGFBP-3 were of borderline significance (r = -0.12, P = 0.06 and r = -0.11, P = 0.07, respectively).","title":"Dietary soy and fats in relation to serum insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 levels in premenopausal Jap..."},{"docid":"MED-3316","text":"BACKGROUND: Between November, 2006, and May, 2008, a subacute neurological syndrome affected workers from two swine abattoirs in Minnesota and Indiana who had occupational exposure to aerosolised porcine brain. We aimed to describe the pathogenic and immunological characteristics of this illness. METHODS: All patients from two abattoirs who presented or were referred to the Mayo Clinic (Rochester, MN, USA) with neurological symptoms were included. We recorded details of exposure to aerosolised brain tissue and did comprehensive neurological, laboratory, neuroimaging, electrophysiological, pathological, and autoimmune serological assessments. Healthy controls were recruited from the community and from workers at the plant in Minnesota. FINDINGS: 24 patients were identified (21 from Minnesota, three from Indiana). The shortest duration from first exposure to symptom onset was 4 weeks. No infectious agent that could trigger disease was identified. All patients developed polyradiculoneuropathy, which was usually sensory predominant and painful. Two patients had initial CNS manifestations: transverse myelitis and meningoencephalitis. Nerve conduction studies localised abnormalities to the most proximal and distal nerve segments. Quantitative sensory and autonomic testing revealed involvement of large and small sensory fibres and sweat fibres. MRI showed prominent abnormalities of roots and ganglia. Nerve biopsies identified mild demyelination, axonal degeneration, and perivascular inflammation. Protein concentrations were high in the CSF of 18 (86%) of 21 patients. Sera from all patients and 29 (34%) of 85 unaffected workplace controls (but none of 178 community controls) had a distinctive neural-reactive IgG; 75% of patients' sera contained an IgG specific to myelin basic protein. Seropositivity correlated directly with exposure risk in patients and controls. 17 patients required immunomodulatory therapies, six improved spontaneously, and one was lost to follow-up after exposure stopped. INTERPRETATION: The neurological disorder described is autoimmune in origin and is related to occupational exposure to multiple aerosolised porcine brain tissue antigens. The pattern of nerve involvement suggests vulnerability of nerve roots and terminals where the blood-nerve barrier is most permeable. FUNDING: Mayo Clinic Foundation; Minnesota Department of Health; Centers for Disease Control and Prevention. Copyright 2010 Elsevier Ltd. All rights reserved.","title":"An outbreak of neurological autoimmunity with polyradiculoneuropathy in workers exposed to aerosolised porcine neural tissue: a descriptive study."},{"docid":"MED-2507","text":"Increased plasma levels of adiponectin, metformin therapy of diabetes, rapamycin administration in transplant patients, and lifelong consumption of low-protein plant-based diets have all been linked to decreased risk for various cancers. These benefits may be mediated, at least in part, by down-regulated activity of the mTORC1 complex, a key regulator of protein translation. By boosting the effective availability of the translation initiator eIF4E, mTORC1 activity promotes the translation of a number of \"weak\" mRNAs that code for proteins, often up-regulated in cancer, that promote cellular proliferation, invasiveness, and angiogenesis, and that abet cancer promotion and chemoresistance by opposing apoptosis. Measures which inhibit eIF4E activity, either directly or indirectly, may have utility not only for cancer prevention, but also for the treatment of many cancers in which eIF4E drives malignancy. Since eIF4E is overexpressed in many cancers, strategies which target eIF4E directly--some of which are now being assessed clinically--may have the broadest efficacy in this regard. Many of the \"weak\" mRNAs coding for proteins that promote malignant behavior or chemoresistance are regulated transcriptionally by NF-kappaB and/or Stat3, which are active in a high proportion of cancers; thus, regimens concurrently targeting eIF4E, NF-kappaB, and Stat3 may suppress these proteins at both the transcriptional and translational levels, potentially achieving a very marked reduction in their expression. Copyright © 2011 Elsevier Ltd. All rights reserved.","title":"mTORC1 activity as a determinant of cancer risk--rationalizing the cancer-preventive effects of adiponectin, metformin, rapamycin, and low-protein ..."},{"docid":"MED-2509","text":"DR (dietary restriction), or reduced food intake without malnutrition, is associated with extended longevity, improved metabolic fitness and increased stress resistance in a wide range of organisms. DR is often referred to as calorie restriction, implying that reduced energy intake is responsible for its widespread and evolutionarily conserved benefits. However, recent data indicate dietary amino acid restriction as a key mediator of DR benefits. In fruitflies, an imbalance in essential amino acid intake is thought to underlie longevity benefits of DR. In mammals, reduced dietary protein or essential amino acid intake can extend longevity, improve metabolic fitness and increase stress resistance. In the present paper we review two evolutionarily conserved signal transduction pathways responsible for sensing amino acid levels. The eIF2α (eukaryotic initiation factor 2α) kinase GCN2 (general amino acid control non-derepressible 2) senses the absence of one or more amino acids by virtue of direct binding to uncharged cognate tRNAs. The presence of certain amino acids, such as leucine, permits activation of the master growth regulating kinase TOR (target of rapamycin). These two signal transduction pathways react to amino acid deprivation by inhibiting general protein translation while at the same time increasing translation of specific mRNAs involved in restoring homoeostasis. Together, these pathways may contribute to the regulation of longevity, metabolic fitness and stress resistance.","title":"Amino acid sensing in dietary-restriction-mediated longevity: roles of signal-transducing kinases GCN2 and TOR"},{"docid":"MED-2288","text":"In recent years there has been considerable interest in the benefits of high-protein diets. This study determined current usual intake of protein in America. Using the most recent data from the National Health and Nutrition Examination Survey, 2003-2004, usual protein intake for Americans aged 2+ years was estimated. Usual protein intake was calculated on a grams per day, grams per kilogram ideal body weight, and a percentage of calories basis. Protein intake averaged 56 +/- 14 g/d in young children, increased to a high of approximately 91 +/- 22 g/d in adults aged 19-30 y, and decreased to approximately 66 +/- 17 g/d in the elderly. The percentage of the male population who consumed less than the estimated average requirement was very low. Our estimates indicated that 7.7% of adolescent females and 7.2-8.6% of older adult women reported consuming protein levels below their estimated average requirement. The median intake of protein on a percentage of calories basis ranged from 13.4% in children aged 4-8 y to 16.0% in men aged 51-70 y. Even the 95th percentile of protein intake did not approach the highest acceptable macronutrient distribution range of 35% for an age/sex group. The highest 95th percentile of protein intake was 20.8% of calories in men aged 51-70 y. Given the demonstrated benefits of higher protein intake on weight management, sarcopenia, and other physiologic functions, efforts should be undertaken to ensure that Americans consume the recommended amount of protein (17-21% of calories as expected from MyPyramid food patterns).","title":"Current protein intake in America: analysis of the National Health and Nutrition Examination Survey, 2003-2004."},{"docid":"MED-2645","text":"The development of the male reproductive ducts and external genitalia in vertebrates is dependent on elevated androgen concentrations during embryonic development and the period of postnatal growth. We have observed that a population of juvenile alligators living on Lake Apopka exhibit significantly smaller penis size (24% average decrease) and lower plasma concentrations of testosterone (70% lower concentrations) when compared to animals of similar size on Lake Woodruff. In addition to smaller phalli, no relationship exists between plasma testosterone concentrations and penile size in males from Lake Apopka, whereas a positive relationship exists for males from Lake Woodruff. The alligators on Lake Apopka are known to have elevated concentrations of the antiandrogenic DDT breakdown product p.p'-DDE stored in their fat. We suggest a number of hypotheses that could explain the modification in the phenotype of the juvenile male living in Lake Apopka. These modifications in phenotype include a smaller penis size, lower plasma androgen concentrations, and lack of responsiveness of the penis to the plasma androgens present.","title":"Reduction in penis size and plasma testosterone concentrations in juvenile alligators living in a contaminated environment."},{"docid":"MED-3956","text":"Early onset of puberty may confer adverse health consequences. Thus, modifiable factors influencing the timing of puberty are of public health interest. Childhood overweight as a factor in the earlier onset of menarche has been supported by prospective evidence; nonetheless, its overall contribution may have been overemphasized, since secular trends toward a younger age at menarche have not been a universal finding during the recent obesity epidemic. Current observational studies suggest notable associations between dietary intakes and pubertal timing beyond contributions to an energy imbalance: children with the highest intakes of vegetable protein or animal protein experience pubertal onset up to 7 months later or 7 months earlier, respectively. Furthermore, girls with high isoflavone intakes may experience the onset of breast development and peak height velocity approximately 7-8 months later. These effect sizes are on the order of those observed for potentially neuroactive steroid hormones. Thus, dietary patterns characterized by higher intakes of vegetable protein and isoflavones and lower intakes of animal protein may contribute to a lower risk of breast cancer or a lower total mortality. © 2012 International Life Sciences Institute.","title":"Beyond overweight: nutrition as an important lifestyle factor influencing timing of puberty."},{"docid":"MED-3148","text":"We examined the resting metabolic rate (RMR) and sympathetic nervous system activity of young male vegetarians (n = 17) and nonvegetarians (n = 40). Subjects were characterized for RMR by indirect calorimetry, norepinephrine kinetics from infusions of tritiated norepinephrine, energy and macronutrient intake from a 3-day food diary, and body composition by underwater weighing. Vegetarians reported a greater relative intake of carbohydrates (62% +/- 5% v 51% +/- 6%, P < .01) and a lower relative intake of fat (25% +/- 5% v 33% +/- 6%, P < .01) than nonvegetarians, whereas no differences were observed in daily energy intake, body composition, or maximal aerobic capacity (VO2max) between groups. Vegetarians exhibited an 11% higher absolute RMR (1.29 +/- 0.15 v 1.16 +/- 0.13 kcal/min, P < .01), a higher plasma concentration of norepinephrine (216 +/- 33 v 165 +/- 18 pg/mL, P < .01), and a greater norepinephrine appearance rate (0.50 +/- 0.08 v 0.36 +/- 0.09 micrograms/min, P < .01) than nonvegetarians. After statistically controlling for differences in relative amounts of carbohydrate and fat in the diet and for norepinephrine concentrations, no significant differences in adjusted RMR between vegetarians and nonvegetarians were noted. These results suggest that the higher RMR observed in young male vegetarians is partially mediated by differences in dietary macronutrient composition and increased sympathetic nervous system activity.","title":"Sympathetic nervous system activity and resting metabolic rate in vegetarians."},{"docid":"MED-1615","text":"Hyperinsulinemia, hypertension, hypertriglyceridemia and obesity are independent risk factors for coronary artery disease and are often found in the same person. This study investigated the effects of an intensive, 3-week, dietary and exercise program on these risk factors. The group was divided into diabetic patients (non-insulin-dependent diabetes mellitus [NIDDM], n = 13), insulin-resistant persons (n = 29) and those with normal insulin, less than or equal to 10 microU/ml (n = 30). The normal groups had very small but statistically significant decreases in all of the risk factors. The patients with NIDDM had the greatest decreases. Insulin was reduced from 40 +/- 15 to 27 +/- 11 microU/ml, blood pressure from 142 +/- 9/83 +/- 3 to 132 +/- 6/71 +/- 3 mm Hg, triglycerides from 353 +/- 76 to 196 +/- 31 mg/dl and body mass index from 31.1 +/- 4.0 to 29.7 +/- 3.7 kg/m2. Although there was a significant weight loss for the group with NIDDM, resulting in the decrease in body mass index, 8 of 9 patients who were initially overweight were still overweight at the end of the program, and 5 of the 8 were still obese (body mass index greater than 30 kg/m2), indicating that normalization of body weight is not a requisite for a reduction or normalization of other risk factors. Insulin was reduced from 18.2 +/- 1.8 to 11.6 +/- 1.2 microU/ml in the insulin-resistant group, with 17 of the 29 subjects achieving normal fasting insulin (less than 10 microU/ml).(ABSTRACT TRUNCATED AT 250 WORDS)","title":"Role of diet and exercise in the management of hyperinsulinemia and associated atherosclerotic risk factors."},{"docid":"MED-3308","text":"An occupational health survey conducted in a workshop in which asbestos cement was used showed initial atmospheric asbestos levels ranging from 1.9 to 27.5 fibres per millilitre of air. Radiological changes suggestive of asbestos-related pleural disease were found in 2 workers (2.5%), while 3 (3.8%) had borderline features of asbestosis. The survey confirmed that uncontrolled and hazardous use of asbestos continues in industry despite public awareness of its dangers and the Asbestos Regulations of 1987.","title":"Third wave of asbestos-related disease from secondary use of asbestos. A case report from industry."},{"docid":"MED-1224","text":"In adults, dietary protein seems to induce weight loss and dairy proteins may be insulinotropic. However, the effect of milk proteins in adolescents is unclear. The objective was to test whether milk and milk proteins reduce body weight, waist circumference, homeostatic model assessment, plasma insulin, and insulin secretion estimated as the plasma C-peptide concentration in overweight adolescents. Overweight adolescents (n = 203) aged 12-15 y with a BMI of 25.4 ± 2.3 kg/m(2) (mean ± SD) were randomized to 1 L/d of skim milk, whey, casein, or water for 12 wk. All milk drinks contained 35 g protein/L. Before randomization, a subgroup of adolescents (n = 32) was studied for 12 wk before the intervention began as a pretest control group. The effects of the milk-based test drinks were compared with baseline (wk 0), the water group, and the pretest control group. Diet and physical activity were registered. Outcomes were BMI-for-age Z-scores (BAZs), waist circumference, plasma insulin, homeostatic model assessment, and plasma C-peptide. We found no change in BAZ in the pretest control and water groups, whereas it was greater at 12 wk in the skim milk, whey, and casein groups compared with baseline and with the water and pretest control groups. The plasma C-peptide concentration increased from baseline to wk 12 in the whey and casein groups and increments were greater than in the pretest control (P < 0.02). There were no significant changes in plasma C-peptide in the skim milk or water group. These data suggest that high intakes of skim milk, whey, and casein increase BAZs in overweight adolescents and that whey and casein increase insulin secretion. Whether the effect on body weight is primary or secondary to the increased insulin secretion remains to be elucidated.","title":"Skim milk, whey, and casein increase body weight and whey and casein increase the plasma C-peptide concentration in overweight adolescents."},{"docid":"MED-3288","text":"In the fall of 2007, the Minnesota Department of Health was notified of 11 cases of an unexplained neurological illness, all linked to a pork processing plant, Quality Pork Processors, Inc., in Austin, MN. The cluster of workers had been experiencing similar symptoms, including fatigue, pain, numbness, and tingling in their extremities as well as weakness. The symptoms were described as more sensory than motor, and all patients had evidence of polyradiculoneuropathy with signs of nerve root irritation. An epidemiological investigation revealed that the only commonality between cases was their exposure to a pork brain extraction procedure involving compressed air. As relatives of the cases remained asymptomatic and all cultures for known pathogens were negative, the etiology of the syndrome seemed not to be infectious. Clinically, the syndrome was most akin to chronic inflammatory demyelinating polyneuropathy. Laboratory tests corroborated the clinical findings, revealing inflammation of peripheral nerves and nerve roots; however, these cases also had features clinically distinct from chronic inflammatory demyelinating polyneuropathy as well as laboratory testing revealing a novel immunoglobulin G immunostaining pattern. This suggested that the observed inflammation was the result of 1 or more unidentified antigens. This syndrome was ultimately dubbed progressive inflammatory neuropathy and was theorized to be an autoimmune reaction to aerosolized porcine neural tissue. Since the investigation's outset, 18 cases of progressive inflammatory neuropathy have been identified at the Minnesota pork processing plant, with 5 similar cases at an Indiana plant and 1 case at a Nebraskan plant. The plants in which cases have been identified have since stopped the use of compressed air in removing pork brains. All cases have stabilized or improved, with some requiring immunosuppressive and analgesic treatment. The study of progressive inflammatory neuropathy is ongoing, and the details of this investigation highlight the value of epidemiological principles in the identification and containment of outbreaks while researchers attempt to uncover the unique pathophysiology and potential etiology of the illness. Mt Sinai J Med 76:442-447, 2009. (c) 2009 Mount Sinai School of Medicine.","title":"Outbreak of progressive inflammatory neuropathy following exposure to aerosolized porcine neural tissue."},{"docid":"MED-5185","text":"There is some evidence that dietary factors may modify the risk of squamous cell carcinoma (SCC) of the skin, but the association between food intake and SCC has not been evaluated prospectively. We examined the association between food intake and SCC incidence among 1,056 randomly selected adults living in an Australian sub-tropical community. Measurement-error corrected estimates of intake in 15 food groups were defined from a validated food frequency questionnaire in 1992. Associations with SCC risk were assessed using Poisson and negative binomial regression to the persons affected and tumour counts, respectively, based on incident, histologically confirmed tumours occurring between 1992 and 2002. After multivariable adjustment, none of the food groups was significantly associated with SCC risk. Stratified analysis in participants with a past history of skin cancer showed a decreased risk of SCC tumours for high intakes of green leafy vegetables (RR = 0.45, 95% CI = 0.22-0.91; p for trend = 0.02) and an increased risk for high intake of unmodified dairy products (RR = 2.53, 95% CI: 1.15-5.54; p for trend = 0.03). Food intake was not associated with SCC risk in persons who had no past history of skin cancer. These findings suggest that consumption of green leafy vegetables may help prevent development of subsequent SCCs of the skin among people with previous skin cancer and that consumption of unmodified dairy products, such as whole milk, cheese and yoghurt, may increase SCC risk in susceptible persons. Copyright 2006 Wiley-Liss, Inc.","title":"Food intake and risk of squamous cell carcinoma of the skin in a community: the Nambour skin cancer cohort study."},{"docid":"MED-4047","text":"The total phenolic contents and antioxidant activities of garlics from California, Oregon, Washington, and New York were determined by Fourier transform infrared (FT-IR) spectroscopy (400-4000 cm(-1)). The total phenolic content was quantified [Folin-Ciocalteu assay (FC)] and three antioxidant activity assays, 2,2-diphenyl-picrylhydrazyl (DPPH) assay, Trolox equivalent antioxidant capacity (TEAC) assay, and ferric reducing antioxidant power (FRAP), were employed for reference measurements. Four independent partial least-squares regression (PLSR) models were constructed with spectra from 25 extracts and their corresponding FC, DPPH, TEAC, and FRAP with values for 20 additional extracts predicted (R > 0.95). The standard errors of calibration and standard error of cross-validation were <1.45 (TEAC), 0.36 (FRAP), and 0.33 μmol Trolox/g FW (DPPH) and 0.55 mg gallic acid/g FW (FC). Cluster and dendrogram analyses could segregate garlic grown at different locations. Hydroxyl and phenolic functional groups most closely correlated with garlic antioxidant activity.","title":"Determination of total phenolic content and antioxidant activity of garlic (Allium sativum) and elephant garlic (Allium ampeloprasum) by attenuated..."},{"docid":"MED-3130","text":"Although soy phytoestrogens have been postulated to exert a protective effect against breast cancer, the attendant mechanisms, in particular epigenetics underpinnings, have remained elusive. We investigated the putative effects on DNA methylation by two naturally occurring isoflavones, genistein and daidzein, in a study of the BRCA1 and BRCA2 oncosuppressor genes in breast cancer cell lines (MCF-7, MDA-MB 231, and MCF10a). A demethylant agent, the 5-azacytidine, and a methylant, the budesonide, were used as treatment controls. DNA methylation of BRCA1 and BRCA2 was investigated with methylated DNA immunoprecipitation coupled with PCR. In parallel, protein expression was determined by Western blot, immunohistochemistry, and confocal microscopy. Our results suggest that treatment with 18.5 μM Genistein or 78.5 μM Daidzein might reverse DNA hypermethylation and restore the expression of the oncosuppressor genes BRCA1 and BRCA2. 5-Azacitydine also enhanced the reexpression of these genes while budesonide had an opposite effect. To the best of our knowledge, these observations, while requiring replication, provide new evidence on potential epigenetic mechanisms by which genistein and daidzein might contribute to regulation of the BRCA1 and BRCA2. Future studies are warranted on whether the demethylating effect of genistein and daidzein is global or focused on select candidate genes.","title":"Can soy phytoestrogens decrease DNA methylation in BRCA1 and BRCA2 oncosuppressor genes in breast cancer?"},{"docid":"MED-2204","text":"The initial investigation of the nature of the proteins in the tuber of sweet potato (Ipomoea batatas Lam.) revealed a globulin-designated \"ipomoein,\" which was reported by Jones and Gersdorff, (1931). Later, \"ipomoein\" was renamed \"sporamin\" and was found to be a major storage protein that accounted for over 80% of the total protein in the tuberous root. To date, sporamin has been studied by a series of biochemical and molecular approaches. The first purification of sporamin into two major fractions, A and B, was successfully completed in 1985. Several characteristics of the protein, such as the diversification of the nucleotide sequences in the gene family, the protein structure, the biological functions of storage, defense, inhibitory activity and ROS scavenging, were identified. In the past decade, sporamin was classified as a Kunitz-type trypsin inhibitor, and its insect-resistance capability has been examined in transgenic tobacco and cauliflower plants, indicating the multiple functions of this protein has evolved to facilitate the growth and development of sweet potato. Sporamin is constitutively expressed in the tuberous root and is not normally expressed in the stem or leaves. However, this protein is expressed systemically in response to wounding and other abiotic stresses. These dual expression patterns at the transcriptional level revealed that the complex regulatory mechanism of sporamin was modulated by environmental stresses. The versatile functions of sporamin make this storage protein a good research model to study molecular evolution, regulatory mechanisms and physiological functions in plants. This review summarizes and discusses recent approaches and future perspectives in agricultural biotechnology. Copyright © 2012 Elsevier Inc. All rights reserved.","title":"Multiple biological functions of sporamin related to stress tolerance in sweet potato (Ipomoea batatas Lam)."},{"docid":"MED-2657","text":"BACKGROUND: Japanese cedar pollinosis, caused by the pollen of the Japanese cedar tree (Cryptomeria japonica), is the commonest seasonal allergic disease in Japan. A number of epidemiological surveys have been reported on Japanese cedar pollinosis, but it has never been assessed systematically or quantitatively. To confirm the increasing prevalence of Japanese cedar pollinosis and related factors, we conducted a meta-regression analysis on population-based surveys in Japan. METHODS: We searched for data from population-based surveys in which serological methods were used to test all participants. Weighted regression of logit-transformed prevalence and sensitization rates were used to evaluate the effects of the year of survey, age, and degree of urbanization. We also analyzed the relationship between prevalence and sensitization rate. RESULTS: Thirty-eight reports with 27 subgroups for prevalence and 134 subgroups for sensitization rate were selected from the literature published in the years between 1986 and 2000. The Japanese cedar pollen sensitization rate was found to be significantly correlated with the year of survey, age, and degree of urbanization (adjusted R(2) = 0.55). The coefficient for the correlation between the prevalence and the sensitization rate revealed a statistically significant correlation (Pearson's r = 0.70, p < 0.001). CONCLUSIONS: The prevalence of Japanese cedar pollinosis among adolescents was predicted to be 28.7% in metropolitan areas and 24.5% in the general population in urban areas in the year 2004, derived from the estimated sensitization rate and the relationship between sensitization rate and prevalence. The prevalence of Japanese cedar pollinosis increased 2.6-fold between 1980 and 2000, and the prevalence differed considerably according to age and degree of urbanization. Copyright (c) 2005 S. Karger AG, Basel","title":"Increasing prevalence of Japanese cedar pollinosis: a meta-regression analysis."},{"docid":"MED-3877","text":"OBJECTIVES: Dietary factors may influence the prostate and have an impact on prostatic growth and disease. A small number of studies have suggested that flaxseed-supplemented, fat-restricted diets may thwart prostate cancer growth in both animals and humans. Unknown, however, is the potential effect of such a diet on benign prostatic epithelium. METHODS: We undertook a pilot study to explore whether a flaxseed-supplemented, fat-restricted diet affects the proliferation rates in benign epithelium. We also explored the effects on circulating levels of prostate-specific antigen (PSA), total testosterone, and cholesterol. Fifteen men who were scheduled to undergo repeat prostate biopsy were instructed to follow a low-fat (less than 20% kcal), flaxseed-supplemented (30 g/day) diet and were provided with a supply of flaxseed to last throughout the 6-month intervention period. The PSA, total testosterone, and cholesterol levels were determined at baseline and at 6 months of follow-up. Reports from the original and repeat biopsies were compared, and proliferation (MIB-1) rates were quantified in the benign prostatic epithelium. RESULTS: Statistically significant decreases in PSA (8.47 +/- 3.82 to 5.72 +/- 3.16 ng/mL; P = 0.0002) and cholesterol (241.1 +/- 30.8 to 213.3 +/- 51.2 mg/dL; P = 0.012) were observed. No statistically significant change was seen in total testosterone (434.5 +/- 143.6 to 428.3 +/- 92.5 ng/dL). Although 6-month repeat biopsies were not performed in 2 cases because of PSA normalization, of the 13 men who underwent repeat biopsy, the proliferation rates in the benign epithelium decreased significantly from 0.022 +/- 0.027 at baseline to 0.007 +/- 0.014 at 6 months of follow-up (P = 0.0168). CONCLUSIONS: These pilot data suggest that a flaxseed-supplemented, fat-restricted diet may affect the biology of the prostate and associated biomarkers. A randomized controlled trial is needed to determine whether flaxseed supplementation, a low-fat diet, or a combination of the two regimens may be of use in controlling overall prostatic growth.","title":"Pilot study to explore effects of low-fat, flaxseed-supplemented diet on proliferation of benign prostatic epithelium and prostate-specific antigen."},{"docid":"MED-5181","text":"Recent evidence suggests overall dietary patterns, rather than specific dietary components, may be a better predictor of colorectal adenomas or cancers. Using cluster analysis, we aimed to assess the association between dietary patterns and colorectal adenomas and whether adjusting for total energy consumption prior to creating clusters affects this relation. Data from a case-control study of 725 individuals undergoing a colonoscopy were utilized. Cases (n = 203) had > or =1 adenoma on colonoscopy, and controls (n = 522) were those who had no adenomas. Dietary data were obtained from an FFQ. Daily intake for 18 different food groups was calculated. The values were transformed into Z-scores. Participants were first clustered without energy adjustment, then again based on their consumption per 1000 kcal (4187 kJ). There was no association between dietary patterns and colorectal adenomas without energy adjustment prior to creating dietary clusters, as clusters formed as a by-product of energy consumption. After adjusting for energy consumption, 3 distinct clusters emerged: 1) high fruit-low meat cluster; 2) high vegetable-moderate meat cluster; and 3) high meat cluster. After adjusting for potential confounders, the high vegetable-moderate meat cluster (odds ratio [OR] 2.17: [95% CI] 1.20-3.90) and high meat cluster (OR 1.70: [95% CI] 1.04-2.80) were at significantly increased odds of having had an adenoma compared with the high fruit-low meat cluster. A high-fruit, low-meat diet appears to be protective against colorectal adenomas compared with a dietary pattern of increased vegetable and meat consumption.","title":"A diet high in fruits and low in meats reduces the risk of colorectal adenomas."},{"docid":"MED-5183","text":"Dietary phytochemical compounds, including isoflavones and isothiocyanates, may inhibit cancer development but have not yet been examined in prospective epidemiologic studies of ovarian cancer. The authors have investigated the association between consumption of these and other nutrients and ovarian cancer risk in a prospective cohort study. Among 97,275 eligible women in the California Teachers Study cohort who completed the baseline dietary assessment in 1995–1996, 280 women developed invasive or borderline ovarian cancer by December 31, 2003. Multivariable Cox proportional hazards regression, with age as the timescale, was used to estimate relative risks and 95% confidence intervals; all statistical tests were two sided. Intake of isoflavones was associated with lower risk of ovarian cancer. Compared with the risk for women who consumed less than 1 mg of total isoflavones per day, the relative risk of ovarian cancer associated with consumption of more than 3 mg/day was 0.56 (95% confidence interval: 0.33, 0.96). Intake of isothiocyanates or foods high in isothiocyanates was not associated with ovarian cancer risk, nor was intake of macronutrients, antioxidant vitamins, or other micronutrients. Although dietary consumption of isoflavones may be associated with decreased ovarian cancer risk, most dietary factors are unlikely to play a major role in ovarian cancer development.","title":"Diet and Risk of Ovarian Cancer in the California Teachers Study Cohort"},{"docid":"MED-2464","text":"BACKGROUND: In recent decades, children's diet quality has changed and asthma prevalence has increased, although it remains unclear if these events are associated. OBJECTIVE: To examine children's total and component diet quality and asthma and airway hyperresponsiveness (AHR), a proxy for asthma severity. METHODS: Food frequency questionnaires adapted from the Nurses' Health Study and supplemented with foods whose nutrients which have garnered interest of late in relation to asthma were administered. From these data, diet quality scores (total and component), based on the Youth Healthy Eating Index (YHEI adapted) were developed. Asthma assessments were performed by pediatric allergists and classified by atopic status: Allergic asthma (≥1 positive skin prick test to common allergens >3 mm compared to negative control) versus non-allergic asthma (negative skin prick test). AHR was assessed via the Cockcroft technique. Participants included 270 boys (30% with asthma) and 206 girls (33% with asthma) involved in the 1995 Manitoba Prospective Cohort Study nested case-control study. Logistic regression was used to examine associations between diet quality and asthma, and multinomial logistic regression was used to examine associations between diet quality and AHR. RESULTS: Four hundred seventy six children (56.7% boys) were seen at 12.6 ± 0.5 years. Asthma and AHR prevalence were 26.2 and 53.8%, respectively. In fully adjusted models, high vegetable intake was protective against allergic asthma (OR 0.49; 95% CI 0.29-0.84; P < 0.009) and moderate/severe AHR (OR 0.58; 0.37-0.91; P < 0.019). CONCLUSIONS: Vegetable intake is inversely associated with allergic asthma and moderate/severe AHR. Copyright © 2012 Wiley Periodicals, Inc.","title":"Low vegetable intake is associated with allergic asthma and moderate-to-severe airway hyperresponsiveness."},{"docid":"MED-4894","text":"SUMMARY: This cross-sectional study showed that, although vegans had lower dietary calcium and protein intakes than omnivores, veganism did not have adverse effect on bone mineral density and did not alter body composition. INTRODUCTION: Whether a lifelong vegetarian diet has any negative effect on bone health is a contentious issue. We undertook this study to examine the association between lifelong vegetarian diet and bone mineral density and body composition in a group of postmenopausal women. METHODS: One hundred and five Mahayana Buddhist nuns and 105 omnivorous women (average age = 62, range = 50-85) were randomly sampled from monasteries in Ho Chi Minh City and invited to participate in the study. By religious rule, the nuns do not eat meat or seafood (i.e., vegans). Bone mineral density (BMD) at the lumbar spine (LS), femoral neck (FN), and whole body (WB) was measured by DXA (Hologic QDR 4500). Lean mass, fat mass, and percent fat mass were also obtained from the DXA whole body scan. Dietary calcium and protein intakes were estimated from a validated food frequency questionnaire. RESULTS: There was no significant difference between vegans and omnivores in LSBMD (0.74 +/- 0.14 vs. 0.77 +/- 0.14 g/cm(2); mean +/- SD; P = 0.18), FNBMD (0.62 +/- 0.11 vs. 0.63 +/- 0.11 g/cm(2); P = 0.35), WBBMD (0.88 +/- 0.11 vs. 0.90 +/- 0.12 g/cm(2); P = 0.31), lean mass (32 +/- 5 vs. 33 +/- 4 kg; P = 0.47), and fat mass (19 +/- 5 vs. 19 +/- 5 kg; P = 0.77) either before or after adjusting for age. The prevalence of osteoporosis (T scores < or = -2.5) at the femoral neck in vegans and omnivores was 17.1% and 14.3% (P = 0.57), respectively. The median intake of dietary calcium was lower in vegans compared to omnivores (330 +/- 205 vs. 682 +/- 417 mg/day, P < 0.001); however, there was no significant correlation between dietary calcium and BMD. Further analysis suggested that whole body BMD, but not lumbar spine or femoral neck BMD, was positively correlated with the ratio of animal protein to vegetable protein. CONCLUSION: These results suggest that, although vegans have much lower intakes of dietary calcium and protein than omnivores, veganism does not have adverse effect on bone mineral density and does not alter body composition.","title":"Veganism, bone mineral density, and body composition: a study in Buddhist nuns."},{"docid":"MED-3221","text":"Background The finding reported in a previous paper - alkalization of urine facilitates uric acid excretion - is contradictory to what one might expect to occur: because food materials for the alkalization of urine contain fewer purine bodies than those for acidification, less uric acid in alkaline urine should have been excreted than in acid urine. To make clear what component of uric acid excretion mechanisms is responsible for this unexpected finding, we simultaneously collected data for the concentration of both creatinine and uric acid in serum as well as in urine, in order to calculate both uric acid and creatinine clearances. Methods Within the framework of the Japanese government’s health promotion program, we made recipes which consisted of protein-rich and less vegetable-fruit food materials for H + -load (acidic diet) and others composed of less protein and more vegetable-fruit rich food materials (alkaline diet). This is a crossover study within some limitations. Healthy female students, who had no medical problems at the regular physical examination provided by the university, were enrolled in this consecutive 5-day study for each test. From whole-day collected urine, total volume, pH, organic acid, creatinine, uric acid, titratable acid and all cations (Na+,K+,Ca2+,Mg2+,NH4+) and anions (Cl−,SO42−,PO4−) necessary for the estimation of acid–base balance were measured. In the early morning before breakfast of the 1st, 3rd and 5th experimental day, we sampled 5 mL of blood to estimate the creatinine and uric acid concentration in serum. Results and discussion Urine pH reached a steady state 3 days after switching from ordinary daily diets to specified regimens. The amount of acid generated ([SO42−] + organic acid − gut alkali)was linearly related with the excretion of acid (titratable acid + [NH4+] − [HCO3−]), indicating that H + in urine is generated by the metabolic degradation of food materials. Uric acid and excreted urine pH retained a linear relationship, as reported previously. Among the five factors which are associated with calculating clearances for both uric acid and creatinine, we identified a conspicuous difference between acidic and alkaline diets in the uric acid concentration in serum as well as in urine; uric acid in the serum was higher in the acidic group than in the alkaline group, while uric acid in the urine in the acidic group was lower than that in the alkaline group. These changes of uric acid in acidic urine and in serum were reflected in the reduction of its clearance. From these observations, it is considered that uric acid may be reabsorbed more actively in acidic urine than in alkaline urine. Conclusion We conclude that alkalization of urine by eating nutritionally well-designed alkaline -prone food is effective for removing uric acid from the body.","title":"Effect of urine pH changed by dietary intervention on uric acid clearance mechanism of pH-dependent excretion of urinary uric acid"},{"docid":"MED-3786","text":"This article describes the development of a series of choline- and betaine-controlled diets that were served to research subjects as part of an ongoing study of diet requirements in humans. These diets were developed based on the analysis of choline and betaine in individual foods. The calculated diets were compared with analyses of all foods combined into a single sample for each day. The laboratory analyses of choline and betaine in the whole-diet aliquots matched the estimated amounts in the diets that were calculated from the analyses of individual foods. These diets were adjusted for several levels of choline and betaine and were well accepted by research subjects who consumed them for a time period of up to 2 months. This article describes applications of this diet for use in clinical research on methyl-group requirements in humans and for use in clinical practice for counseling the client who requires a choline-controlled diet.","title":"Choline- and betaine-defined diets for use in clinical research and for the management of trimethylaminuria."},{"docid":"MED-5184","text":"We examined the association of dietary lignan intake with estrogen receptor negative (ER-) and ER positive (ER+) breast cancer risk in a breast cancer case-control study. Among premenopausal women only, there was a reduced risk of ER- breast cancer for those in the highest compared to the lowest quartile of lignan intake suggesting that the observed negative association of lignans with breast cancer may be limited to ER- tumors.","title":"Dietary lignan intakes and risk of breast cancer by tumor estrogen receptor status."},{"docid":"MED-3198","text":"BACKGROUND: Despite its high content of saturated fatty acids, cheese does not seem to increase plasma total and LDL-cholesterol concentrations when compared with an equivalent intake of fat from butter. This effect may be due to the high calcium content of cheese, which results in a higher excretion of fecal fat. OBJECTIVES: The objective was to compare the effects of diets of equal fat content rich in either hard cheese or butter or a habitual diet on blood pressure and fasting serum blood lipids, C-reactive protein, glucose, and insulin. We also examined whether fecal fat excretion differs with the consumption of cheese or butter. DESIGN: The study was a randomized dietary intervention consisting of two 6-wk crossover periods and a 14-d run-in period during which the subjects consumed their habitual diet. The study included 49 men and women who replaced part of their habitual dietary fat intake with 13% of energy from cheese or butter. RESULTS: After 6 wk, the cheese intervention resulted in lower serum total, LDL-, and HDL-cholesterol concentrations and higher glucose concentrations than did the butter intervention. Cheese intake did not increase serum total or LDL-cholesterol concentrations compared with the run-in period, during which total fat and saturated fat intakes were lower. Fecal fat excretion did not differ between the cheese and butter periods. CONCLUSION: Cheese lowers LDL cholesterol when compared with butter intake of equal fat content and does not increase LDL cholesterol compared with a habitual diet. This trial is registered at clinicaltrials.gov as NCT01140165.","title":"Cheese intake in large amounts lowers LDL-cholesterol concentrations compared with butter intake of equal fat content."},{"docid":"MED-3369","text":"Background: Strategies are needed to increase children's intake of a variety of vegetables, including vegetables that are not well liked. Objective: We investigated whether incorporating puréed vegetables into entrées to reduce the energy density (ED; in kcal/g) affected vegetable and energy intake over 1 d in preschool children. Design: In this crossover study, 3- to 5-y-old children (n = 40) were served all meals and snacks 1 d/wk for 3 wk. Across conditions, entrées at breakfast, lunch, dinner, and evening snack were reduced in ED by increasing the proportion of puréed vegetables. The conditions were 100% ED (standard), 85% ED (tripled vegetable content), and 75% ED (quadrupled vegetable content). Entrées were served with unmanipulated side dishes and snacks, and children were instructed to eat as much as they liked. Results: The daily vegetable intake increased significantly by 52 g (50%) in the 85% ED condition and by 73 g (73%) in the 75% ED condition compared with that in the standard condition (both P < 0.0001). The consumption of more vegetables in entrées did not affect the consumption of the vegetable side dishes. Children ate similar weights of food across conditions; thus, the daily energy intake decreased by 142 kcal (12%) from the 100% to 75% ED conditions (P < 0.05). Children rated their liking of manipulated foods similarly across ED amounts. Conclusion: The incorporation of substantial amounts of puréed vegetables to reduce the ED of foods is an effective strategy to increase the daily vegetable intake and decrease the energy intake in young children. This trial was registered at clinicaltrials.gov as NCT01252433.","title":"Hiding vegetables to reduce energy density: an effective strategy to increase children's vegetable intake and reduce energy intake"},{"docid":"MED-4919","text":"OBJECTIVE: Mass screening for celiac disease is controversial. The objective of this study was to determine whether detection of childhood celiac disease by mass screening improves long-term health status and health-related quality of life. METHODS: We conducted a prospective 10-year follow-up study of 32 children who were aged 2 to 4 years, had celiac disease identified by mass screening, and had a gluten-free diet (19) or a normal gluten-containing diet (13). The follow-up included assessments of general health status, celiac disease-associated symptoms, celiac disease-associated serum antibodies, and health-related quality of life. RESULTS: Ten years after mass screening, 81% of the children were adhering to a gluten-free diet. The health status improved in 66% of the treated children: in 41% by early treatment and in 25% by prevention of the gluten-dependent symptoms that they developed after diagnosis. For 19% of the children, treatment after screening would not have improved their health status, because they had no symptoms at screening and have remained symptom-free while consuming gluten. The health-related quality of life of the children with symptoms improved significantly after 1 year of gluten-free diet. Ten years after screening, the health-related quality of life of the children with celiac disease was similar to that of the reference population. CONCLUSION: Identification by mass screening led 10 years later to health improvement in 66% of children without deterioration of generic health-related quality of life. There is a good compliance after mass screening. In a research setting, delaying treatment for children without symptoms seems to be an option after a positive screening test. Long-term follow-up studies are needed to assess possible long-term complications in untreated, nonsymptomatic celiac disease.","title":"Long-term health and quality-of-life consequences of mass screening for childhood celiac disease: a 10-year follow-up study."},{"docid":"MED-2588","text":"Objective Low-carbohydrate diets and their combination with high-protein diets have been gaining widespread popularity to control weight. In addition to weight loss, they may have favorable short-term effects on the risk factors of cardiovascular disease (CVD). Our objective was to elucidate their long-term effects on mortality and CVD incidence. Data sources MEDLINE, EMBASE, ISI Web of Science, Cochrane Library, and ClinicalTrials.gov for relevant articles published as of September 2012. Cohort studies of at least one year’s follow-up period were included. Review methods Identified articles were systematically reviewed and those with pertinent data were selected for meta-analysis. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) for all-cause mortality, CVD mortality and CVD incidence were calculated using the random-effects model with inverse-variance weighting. Results We included 17 studies for a systematic review, followed by a meta-analysis using pertinent data. Of the 272,216 people in 4 cohort studies using the low-carbohydrate score, 15,981 (5.9%) cases of death from all-cause were reported. The risk of all-cause mortality among those with high low-carbohydrate score was significantly elevated: the pooled RR (95% CI) was 1.31 (1.07–1.59). A total of 3,214 (1.3%) cases of CVD death among 249,272 subjects in 3 cohort studies and 5,081 (2.3%) incident CVD cases among 220,691 people in different 4 cohort studies were reported. The risks of CVD mortality and incidence were not statistically increased: the pooled RRs (95% CIs) were 1.10 (0.98–1.24) and 0.98 (0.78–1.24), respectively. Analyses using low-carbohydrate/high-protein score yielded similar results. Conclusion Low-carbohydrate diets were associated with a significantly higher risk of all-cause mortality and they were not significantly associated with a risk of CVD mortality and incidence. However, this analysis is based on limited observational studies and large-scale trials on the complex interactions between low-carbohydrate diets and long-term outcomes are needed.","title":"Low-Carbohydrate Diets and All-Cause Mortality: A Systematic Review and Meta-Analysis of Observational Studies"},{"docid":"MED-4205","text":"Since the Second World War the consumer behaviour in developed countries changed drastically. Primarily there existed the demand for sufficient food after a period of starvation, afterwards the desire for higher quality was arising, whereas today most people ask for safe and healthy food with high quality. Therefore a united approach comprising consistent standards, sound science and robust controls is required to ensure consumers' health and to maintain consumers' confidence and satisfaction. Chemical analysis along the whole food chain downstream (tracking) from primary production to the consumer and upstream (tracing) from the consumer to primary production is an important prerequisite to ensure food safety and quality. In this frame the focus of the following paper is the \"chemical safety of meat and meat products\" taking into account inorganic as well as organic residues and contaminants, the use of nitrite in meat products, the incidence of veterinary drugs, as well as a Failure Mode and Effect Analysis (FMEA) system assessing (prioritizing) vulnerable food chain steps to decrease or eliminate vulnerability.","title":"Chemical safety of meat and meat products."},{"docid":"MED-2353","text":"Summary Anti-Gal is the most abundant natural antibody in humans, constituting ∼ 1% of immunoglobulins. Anti-Gal is naturally produced also in apes and Old World monkeys. The ligand of anti-Gal is a carbohydrate antigen called the ‘α-gal epitope’ with the structure Galα1-3Galβ1-4GlcNAc-R. The α-gal epitope is present as a major carbohydrate antigen in non-primate mammals, prosimians and New World monkeys. Anti-Gal can contributes to several immunological pathogeneses. Anti-Gal IgE produced in some individuals causes allergies to meat and to the therapeutic monoclonal antibody cetuximab, all presenting α-gal epitopes. Aberrant expression of the α-gal epitope or of antigens mimicking it in humans may result in autoimmune processes, as in Graves' disease. α-Gal epitopes produced by Trypanosoma cruzi interact with anti-Gal and induce ‘autoimmune like’ inflammatory reactions in Chagas' disease. Anti-Gal IgM and IgG further mediate rejection of xenografts expressing α-gal epitopes. Because of its abundance, anti-Gal may be exploited for various clinical uses. It increases immunogenicity of microbial vaccines (e.g. influenza vaccine) presenting α-gal epitopes by targeting them for effective uptake by antigen-presenting cells. Tumour lesions are converted into vaccines against autologous tumour-associated antigens by intra-tumoral injection of α-gal glycolipids, which insert into tumour cell membranes. Anti-Gal binding to α-gal epitopes on tumour cells targets them for uptake by antigen-presenting cells. Accelerated wound healing is achieved by application of α-gal nanoparticles, which bind anti-Gal, activate complement, and recruit and activate macrophages that induce tissue regeneration. This therapy may be of further significance in regeneration of internally injured tissues such as ischaemic myocardium and injured nerves.","title":"Anti-Gal: an abundant human natural antibody of multiple pathogeneses and clinical benefits"},{"docid":"MED-1801","text":"OBJECTIVE: In 1976, the Royal College of Physicians and the British Cardiac Society recommended eating less fatty red meat and more poultry instead because it was lean. However, the situation has changed since that time, with a striking increase in fat content of the standard broiler chicken. The aim of the present study was to report a snapshot of data on fat in chickens now sold to the public. DESIGN: Samples were obtained randomly between 2004 and 2008 from UK supermarkets, farm shops and a football club. The amount of chicken fat was estimated by emulsification and chloroform/methanol extraction. SETTING: Food sold in supermarkets and farms in England. SUBJECTS: Chicken samples. RESULTS: The fat energy exceeded that of protein. There has been a loss of n-3 fatty acids. The n-6:n-3 ratio was found to be as high as 9:1, as opposed to the recommendation of about 2:1. Moreover, the TAG level in the meat and whole bird mostly exceeded the proportion of phospholipids, which should be the higher for muscle function. The n-3 fatty acid docosapentaenoic acid (DPA, 22 : 5n-3) was in excess of DHA (22 : 6n-3). Previous analyses had, as usual for birds, more DHA than DPA. CONCLUSIONS: Traditional poultry and eggs were one of the few land-based sources of long-chain n-3 fatty acids, especially DHA, which is synthesized from its parent precursor in the green food chain. In view of the obesity epidemic, chickens that provide several times the fat energy compared with protein seem illogical. This type of chicken husbandry needs to be reviewed with regard to its implications for animal welfare and human nutrition.","title":"Modern organic and broiler chickens sold for human consumption provide more energy from fat than protein."},{"docid":"MED-3928","text":"Seven patients with Parkinson's disease who experienced severe motor fluctuations in response to levodopa were studied in detail with relation to the effect of dietary protein on their motor function. The levodopa dose for each patient was not changed during the period of study, and no other antiparkinsonian drugs were used. Regular and high-protein diets resulted in a marked elevation in the plasma concentrations of large neutral amino acids (LNAAs) that are known to compete with levodopa for transport across the blood-brain barrier. Despite elevated plasma levodopa levels, all patients with elevated LNAA levels experienced parkinsonian symptoms. When the amino acid level dropped while plasma levodopa levels were elevated, patients experienced relief of these symptoms. On a low-protein diet, LNAA levels remained low and all patients were consistently dyskinetic throughout the day, even though the mean plasma levodopa levels were somewhat lower than when the patients consumed a high-protein diet. A redistribution diet that is virtually protein free until supper and then unrestricted until bedtime is tolerated by patients because this simple manipulation permits near-normal daytime motor function.","title":"Plasma levels of amino acids correlate with motor fluctuations in parkinsonism."},{"docid":"MED-1715","text":"Summary Reduced function mutations in the insulin/IGF-I signaling pathway increase maximal lifespan and health span in many species. Calorie restriction (CR) decreases serum IGF-1 concentration by ~40%, protects against cancer and slows aging in rodents. However, the long-term effects of CR with adequate nutrition on circulating IGF-1 levels in humans are unknown. Here we report data from two long-term CR studies (1 and 6 years) showing that severe CR without malnutrition did not change IGF-1 and IGF-1 : IGFBP-3 ratio levels in humans. In contrast, total and free IGF-1 concentrations were significantly lower in moderately protein-restricted individuals. Reducing protein intake from an average of 1.67 g kg −1 of body weight per day to 0.95 g kg −1 of body weight per day for 3 weeks in six volunteers practicing CR resulted in a reduction in serum IGF-1 from 194 ng mL −1 to 152 ng mL −1 . These findings demonstrate that, unlike in rodents, long-term severe CR does not reduce serum IGF-1 concentration and IGF-1 : IGFBP-3 ratio in humans. In addition, our data provide evidence that protein intake is a key determinant of circulating IGF-1 levels in humans, and suggest that reduced protein intake may become an important component of anticancer and anti-aging dietary interventions.","title":"Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans"},{"docid":"MED-1619","text":"BACKGROUND: Diets rich in carbohydrates with a low glycemic index and with high fiber content are associated with flat post-prandial rises of blood glucose, minimal post-prandial insulin secretion and maintenance of insulin sensitivity. Protective food commodities in the prevention of cardiovascular disease, insulin resistance syndrome or diabetes are crucial components of the vegetarian diet. AIM OF THE STUDY: Insulin resistance values were assessed in relation to different nutrition. Metabolic abnormality is a predictor of age-related diseases and can be more pronounced in obese subjects. Insulin resistance values in normal weight subjects of two different nutritional habits were correlated with age. METHODS: Fasting concentrations of glucose and insulin as well as calculated values of insulin resistance IR (HOMA) were assessed in two nutritional groups of apparently healthy adult subjects (age range 19 - 64 years) with normal weight (body mass index 18.6 - 25.0 kg/m(2)): a vegetarian group (95 long-term lacto-ovo-vegetarians; duration of vegetarianism 10.2 +/- 0.5 years) and a non-vegetarian control group (107 subjects of general population on traditional western diet). Intake of energy and main nutrients (fats, saccharides, proteins) was similar in both groups. RESULTS: Glucose and insulin concentrations and IR (HOMA) values were significantly lower in vegetarians (glucose 4.47 +/- 0.05 vs. 4.71 +/- 0.07 mmol/l; insulin 4.96 +/- 0.23 vs. 7.32 +/- 0.41 mU/l; IR (HOMA) 0.99 +/- 0.05 vs. 1.59 +/- 0.10). IR (HOMA) dependence on age was only significant in subjects on a western diet. A significant increase of IR was found already in the age range 31-40 years, compared to vegetarians and it continued in later age decades. Age independent and low insulin resistance values in vegetarians are a consequence of an effective diet prevention by long-term frequent consumption of protective food. Vegetarians had a significantly higher consumption of whole grain products, pulses, products from oat and barley. CONCLUSION: The results of age independent and low values of insulin resistance document a beneficial effect of long-term vegetarian nutrition in prevention of metabolic syndrome, diabetes and cardiovascular disease.","title":"No evidence of insulin resistance in normal weight vegetarians. A case control study."},{"docid":"MED-2360","text":"Lyme-like illness (also known as southern tick-associated rash illness [STARI] or Masters disease) is vectored by the Lone Star tick (Amblyomma americanum). Lyme-like illness lesions, which are similar to the erythema migrans rash of Lyme disease, tend to have lymphocytic dermal infiltrates. With the exception of Borrelia lonestari, the possible causative agent or agents of Lyme-like illness have not been cultured. More research is needed to fully understand this newly recognized zoonosis. Clinicians are encouraged to increase their knowledge and awareness of this Lyme disease mimic.","title":"STARI, or Masters disease: Lone Star tick-vectored Lyme-like illness."},{"docid":"MED-4051","text":"The food mutagens IQ (2-amino-3-methylimidazo[4,5-f]quinoline) and PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) are heterocyclic amines (HCA), generated when heating proteinaceous food. This study investigates the protective potential of the flavonoids quercetin (Q) and rutin (R) against oxidative stress induced in vitro by IQ and PhIP in lymphocytes from healthy individuals and untreated, newly diagnosed colon cancer patients using the Comet assay. In the presence of up to 500μM Q and R, the DNA damage resulting from a high dose of PhIP (75μM) or IQ (150μM) was significantly reduced (P<0.001) to levels comparable to six times lower IQ or 7.5 times lower PhIP doses. Lymphocytes from colon cancer patients had greater baseline DNA damage than those from healthy individuals (P<0.01) and this higher level of damage was also observed throughout in vitro treatment. Except for the >50years of age group and male gender, confounding factors such as smoking, drinking and/or dietary habits were not found to be significant. In conclusion, flavonoids reduced oxidative stress caused by food mutagens in vitro in lymphocytes of healthy individuals and colon cancer patients. Thus, dietary supplementation with flavonoid-rich vegetables and fruits may prove very effective in protecting against oxidative stress. Copyright © 2011 Elsevier Ltd. All rights reserved.","title":"The protective effect of the flavonoids on food-mutagen-induced DNA damage in peripheral blood lymphocytes from colon cancer patients."},{"docid":"MED-2643","text":"The incidence and/or prevalence of health problems associated with endocrine-disruption have increased. Many chemicals have endocrine-disrupting properties, including bisphenol A, some organochlorines, polybrominated flame retardants, perfluorinated substances, alkylphenols, phthalates, pesticides, polycyclic aromatic hydrocarbons, alkylphenols, solvents, and some household products including some cleaning products, air fresheners, hair dyes, cosmetics, and sunscreens. Even some metals were shown to have endocrine-disrupting properties. Many observations suggesting that endocrine disruptors do contribute to cancer, diabetes, obesity, the metabolic syndrome, and infertility are listed in this paper. An overview is presented of mechanisms contributing to endocrine disruption. Endocrine disruptors can act through classical nuclear receptors, but also through estrogen-related receptors, membrane-bound estrogen-receptors, and interaction with targets in the cytosol resulting in activation of the Src/Ras/Erk pathway or modulation of nitric oxide. In addition, changes in metabolism of endogenous hormones, cross-talk between genomic and nongenomic pathways, cross talk with estrogen receptors after binding on other receptors, interference with feedback regulation and neuroendocrine cells, changes in DNA methylation or histone modifications, and genomic instability by interference with the spindle figure can play a role. Also it was found that effects of receptor activation can differ in function of the ligand.","title":"Endocrine-Disrupting Chemicals: Associated Disorders and Mechanisms of Action"},{"docid":"MED-1655","text":"In 1940, a young German refugee physician scientist at Duke University in Durham, North Carolina began to treat patients with accelerated or \"malignant\" hypertension with a radical diet consisting of only white rice and fruit, with strikingly favorable results. He reported rapid reduction in blood pressure, rapid improvement in renal failure, papilledema, congestive heart failure and other manifestations of this previously fatal illness. This treatment was based on his theory that the kidney had both an excretory and a metabolic function, and that removing most of the sodium and protein burden from this organ enabled it to regain its normal ability to perform its more important metabolic functions. It was also effective in \"ordinary\" hypertension, in the absence of the dramatic vasculopathy of the accelerated form. The results were so dramatic that many experienced physicians suspected him of falsifying data. Among these results was the normalization of the ECG changes seen with hypertension. This paper reviews his published experience with this radical therapy, its controversial rise to fame, and its decline in popularity with the advent of effective antihypertensive drugs. It features the ECG changes seen in this then fatal disease, and the reversal of these changes by the rice diet. This treatment, though very difficult for the patient, produced effects which make it equal or superior to current multi-drug treatment of hypertension. A poorly known but important observation was that patients who were able to follow the regime, and who were slowly guided through a gradual modification of the diet over many months, were able to transition into a very tolerable low fat, largely vegetarian diet, while leading a normal, active life, without medications, indicating that the disease state had been permanently modified. Copyright © 2014 Elsevier Inc. All rights reserved.","title":"An archaeologic dig: a rice-fruit diet reverses ECG changes in hypertension."},{"docid":"MED-3275","text":"In tissue cultures of normal adult and malignant mammalian cells, homocystine has been substituted for methionine in a medium rich in folic acid and cyanocobalamin. Normal adult cells thrive. Three highly malignant cell types from three different species, including man, die.","title":"The Effect of Replacement of Methionine by Homocystine on Survival of Malignant and Normal Adult Mammalian Cells in Culture"},{"docid":"MED-2661","text":"This paper presents the results of an investigation on the occurrence of alkylphenols (APs) and their ethoxylates (APEs) in 8 edible marine species from the Adriatic Sea and tries to estimate the corresponding intake for the Italian population. Two crustaceans, Nephrops norvegicus (Norway lobster) and Squilla mantis (spottail mantis shrimp), plus six fish species, Engraulis enchrascicolus (anchovy), Scomber scombrus (Atlantic mackerel), Merluccius merluccius (European hake), Mullus barbatus (red mullet), Solea vulgaris (common sole) and Lophius piscatorius (angler) were analyzed for their content of nonylphenol (NP), octylphenol (OP) and octylphenol polyethoxylates (OPEs). These compounds were found in all analysed samples. NP was detected at the highest concentrations: 118-399 and 9.5-1431 ng g(-1) fresh weight (fw) respectively in crustaceans and fish. OP was found at respective levels of 2.7-4.7 and 0.3-3.8 ng g(-1) fw in crustaceans and fish, whereas OPE was determined at respective concentrations of 1.2-16.8 and 0.2-21.1 ng g(-1) fw in the same species. These results, together with those from a previous study on 4 edible mollusc, allow to estimate respective daily intakes for NP, OP, and OPE of about 12, 0.1, and 0.1 microg day(-1) for an Italian adult living along the Adriatic Coast. In relation to NP and OP, these intakes are much lower than the doses associated with toxic effects in laboratory animals (9 mg kg(-1) bw for rats). Nevertheless, data of exposure from other sources to these chemicals and others with similar biological characteristics are needed.","title":"Alkylphenols and alkylphenol ethoxylates contamination of crustaceans and fishes from the Adriatic Sea (Italy)."},{"docid":"MED-4313","text":"BACKGROUND: Population-based studies have shown that vegetarians have lower body mass index than nonvegetarians, suggesting that vegetarian diet plans may be an approach for weight management. However, a perception exists that vegetarian diets are deficient in certain nutrients. OBJECTIVE: To compare dietary quality of vegetarians, nonvegetarians, and dieters, and to test the hypothesis that a vegetarian diet would not compromise nutrient intake when used to manage body weight. DESIGN: Cross-sectional analysis of National Health and Nutrition Examination Survey (1999-2004) dietary and anthropometric data. Diet quality was determined using United States Department of Agriculture's Healthy Eating Index 2005. Participants included adults aged 19 years and older, excluding pregnant and lactating women (N = 13,292). Lacto-ovo vegetarian diets were portrayed by intakes of participants who did not eat meat, poultry, or fish on the day of the survey (n = 851). Weight-loss diets were portrayed by intakes of participants who consumed 500 kcal less than their estimated energy requirements (n = 4,635). Mean nutrient intakes and body mass indexes were adjusted for energy, sex, and ethnicity. Using analysis of variance, all vegetarians were compared to all nonvegetarians, dieting vegetarians to dieting nonvegetarians, and nondieting vegetarians to nondieting nonvegetarians. RESULTS: Mean intakes of fiber, vitamins A, C, and E, thiamin, riboflavin, folate, calcium, magnesium, and iron were higher for all vegetarians than for all nonvegetarians. Although vegetarian intakes of vitamin E, vitamin A, and magnesium exceeded that of nonvegetarians (8.3 ± 0.3 vs 7.0 ± 0.1 mg; 718 ± 28 vs 603 ± 10 μg; 322 ± 5 vs 281 ± 2 mg), both groups had intakes that were less than desired. The Healthy Eating Index score did not differ for all vegetarians compared to all nonvegetarians (50.5 ± 0.88 vs 50.1 ± 0.33, P = 0.6). CONCLUSIONS: These findings suggest that vegetarian diets are nutrient dense, consistent with dietary guidelines, and could be recommended for weight management without compromising diet quality. Copyright © 2011 American Dietetic Association. Published by Elsevier Inc. All rights reserved.","title":"A vegetarian dietary pattern as a nutrient-dense approach to weight management: an analysis of the national health and nutrition examination survey..."},{"docid":"MED-3136","text":"The objective of this study was to determine the influence of frequent and long-term consumption of legume seeds on colonic function. Two groups of subjects were studied--one group habitually consumed legume seeds as part of their normal diet, a second group only infrequently consumed legumes. No differences between these groups could be detected for fecal output and frequency, intestinal transit time, VFA excretion or fecal pH during 23-day study periods in which subjects consumed either their usual diet or 100 g red kidney beans, daily. However, the addition of beans to the diets of both groups provided significantly more dietary fiber, and produced greater fecal output and a higher concentration of VFA in feces. Fecal output appeared to be determined by two independent parameters--dietary fiber intake and VFA excretion. Beans provided a physiologically useful source of dietary fiber and favorably influenced colonic function.","title":"Influence of frequent and long-term bean consumption on colonic function and fermentation."},{"docid":"MED-3217","text":"To investigate whether systemic acid-base equilibrium changes with aging in normal adult humans, we reviewed published articles reporting the acid-base composition of arterial, arterialized venous, or capillary blood in age-identified healthy subjects. We extracted or calculated blood hydrogen ion concentration ([H+]), plasma bicarbonate concentration ([HCO3(-)]), blood PCO2, and age, and computed a total of 61 age-group means, distributed among eight 10-year intervals from age 20 to 100 years. Using linear regression analysis, we found that with increasing age, there is a significant increase in the steady-state blood [H+] (p < .001), and reduction in steady-state plasma [HCO3(-)] (p < .001), indicative of a progressively worsening low-level metabolic acidosis. Blood PCO2 decreased with age (p < .05), in keeping with the expected respiratory adaptation to metabolic acidosis. Such age-related increasing metabolic acidosis may reflect in part the normal decline of renal function with increasing age. The role of age-related metabolic acidosis in the pathogenesis of the degenerative diseases of aging warrants consideration.","title":"Age and systemic acid-base equilibrium: analysis of published data."},{"docid":"MED-4918","text":"Background & Aims The historical prevalence and long-term outcome of undiagnosed celiac disease (CD) are unknown. We investigated the long-term outcome of undiagnosed CD and whether the prevalence of undiagnosed CD has changed during the past 50 years. Methods This study included 9,133 healthy young adults at Warren Air Force Base (sera were collected between 1948 and 1954) and 12,768 sex-matched subjects from 2 recent cohorts from Olmsted County, Minnesota, with either similar years of birth (n=5,558) or age at sampling (n=7,210) to that of the Air Force cohort. Sera were tested for tissue transglutaminase and, if abnormal, for endomysial antibodies. Survival was measured during a follow-up period of 45 years in the Air Force cohort. The prevalence of undiagnosed CD between the Air Force cohort and recent cohorts was compared. Results Of 9,133 persons from the Air Force cohort, 14 (0.2%) had undiagnosed CD. In this cohort, during 45 years of follow-up, all-cause mortality was greater in persons with undiagnosed CD than among those who were seronegative (hazard ratio=3.9; 95% CI, 2.0–7.5; P<.001). Undiagnosed CD was found in 68 (0.9%) persons with similar age at sampling and 46 (0.8%) persons with similar years of birth. The rate of undiagnosed CD was 4.5-fold and 4-fold greater in the recent cohorts (respectively) than in the Air Force cohort (both P ≤ .0001). Conclusions During 45 years of follow-up, undiagnosed CD was associated with a nearly 4-fold increased risk of death. The prevalence of undiagnosed CD appears to have increased dramatically in the United States during the past 50 years.","title":"Increased Prevalence and Mortality in Undiagnosed Celiac Disease"},{"docid":"MED-3215","text":"The average American diet, which is high in protein and low in fruits and vegetables, generates a large amount of acid, mainly as sulfates and phosphates. The kidneys respond to this dietary acid challenge with net acid excretion, as well as ammonium and titratable acid excretion. Concurrently, the skeleton supplies buffer by active resorption of bone. Indeed, calciuria is directly related to net acid excretion. Different food proteins differ greatly in their potential acid load, and therefore in their acidogenic effect. A diet high in acid-ash proteins causes excessive calcium loss because of its acidogenic content. The addition of exogenous buffers, as chemical salts or as fruits and vegetables, to a high protein diet results in a less acid urine, a reduction in net acid excretion, reduced ammonium and titratable acid excretion, and decreased calciuria. Bone resorption may be halted, and bone accretion may actually occur. Alkali buffers, whether chemical salts or dietary fruits and vegetables high in potassium, reverse acid-induced obligatory urinary calcium loss. We conclude that excessive dietary protein from foods with high potential renal acid load adversely affects bone, unless buffered by the consumption of alkali-rich foods or supplements.","title":"Excess dietary protein can adversely affect bone."},{"docid":"MED-3229","text":"High-protein (HP) diets exert a hypercalciuric effect at constant levels of calcium intake, even though the effect may depend on the nature of the dietary protein. Lower urinary pH is also consistently observed for subjects consuming HP diets. The combination of these two effects was suspected to be associated with a dietary environment favorable for demineralization of the skeleton. However, increased calcium excretion due to HP diet does not seem to be linked to impaired calcium balance. In contrast, some data indicate that HP intakes induce an increase of intestinal calcium absorption. Moreover, no clinical data support the hypothesis of a detrimental effect of HP diet on bone health, except in a context of inadequate calcium supply. In addition, HP intake promotes bone growth and retards bone loss and low-protein diet is associated with higher risk of hip fractures. The increase of acid and calcium excretion due to HP diet is also accused of constituting a favorable environment for kidney stones and renal diseases. However, in healthy subjects, no damaging effect of HP diets on kidney has been found in either observational or interventional studies and it seems that HP diets might be deleterious only in patients with preexisting metabolic renal dysfunction. Thus, HP diet does not seem to lead to calcium bone loss, and the role of protein seems to be complex and probably dependent on other dietary factors and the presence of other nutrients in the diet.","title":"Protein intake, calcium balance and health consequences."},{"docid":"MED-3313","text":"INTRODUCTION: Asbestos is banned in most Western countries but related malignancies are still of clinical concern because of their long latencies. This review identifies and addresses some controversial occupational and clinical aspects of asbestos-related malignancies. METHODS: Papers published in English from 1980 to 2009 were retrieved from PubMed. A total of 307 original articles were identified and 159 were included. ASSESSMENT OF EXPOSURE: The retrospective assessment of exposure is usually performed by using questionnaires and job exposure matrices and by careful collection of medical history. In this way crucial information about manufacturing processes and specific jobs can be obtained. In addition, fibers and asbestos bodies are counted in lung tissue, broncho-alveolar lavage, and sputum, but different techniques and interlaboratory variability hamper the interpretation of reported measurements. SCREENING FOR MALIGNANCIES: The effectiveness of low-dose chest CT screening in exposed workers is debatable. Several biomarkers have also been considered to screen individuals at risk for lung cancer and mesothelioma but reliable signatures are still missing. ATTRIBUTION OF LUNG CANCER: Exposures correlating with lung cancer are high and in the same range where asbestosis occurs. However, the unresolved question is whether the presence of fibrosis is a requirement for the attribution of lung cancer to asbestos. The etiology of lung cancer is difficult to define in cases of low-level asbestos exposure and concurrent smoking habits. MESOTHELIOMA: The diagnosis of malignant mesothelioma may also be difficult, because of procedures in sampling, fixation, and processing, and uses of immunohistochemical probes. CONCLUSIONS: Assessment of exposure is crucial and requires accurate medical and occupational histories. Quantitative analysis of asbestos body burden is better performed in digested lung tissues by counting asbestos bodies by light microscopy and/or uncoated fibers by transmission electron microscopy. The benefits of screenings for asbestos-related malignancies are equivocal. The attribution of lung cancer to asbestos exposure is difficult in a clinical setting because of the need to assess asbestos body burden and the fact that virtually all these patients are also tobacco smokers or former smokers. Given the premise that asbestosis is necessary to causally link lung cancer to asbestos, it follows that the assessment of both lung fibrosis and asbestos body burden is necessary.","title":"Occupational toxicology of asbestos-related malignancies."},{"docid":"MED-2366","text":"Glycoconjugates and their antibodies are vital components of host-tumor interaction. This review concentrates on the oncological implications of research concerning the alpha gal triad; the alpha 1-->3 galactosyl epitope (alpha Gal), the enzyme responsible for its construction, alpha 1,3 galactosyl transferase (alpha 1-3GT), and its associated antibody: anti-gal. Alpha gal epitopes, previously assumed to be absent from human tissue, have been demonstrated on several human cancer cell lines, senescent red blood cells, and Graves' disease thyrocytes. Alpha-gal presence on neoplastic lines is correlated with increased metastatic formation in animal models. The mechanisms of human response to these neoantigens are complex, as natural anti-gal antibodies exist in high titers in normal sera, thus predicting immunological recognition of cells expressing alpha gal epitopes. Hypotheses vary regarding the pathogenic contributions of metastasis-associated phenomena such as de novo expression of alpha gal and its unmasking by desialylation. The means by which alpha gal is sporadically expressed in human tissue remain unknown, as the galactosyl transferase which produces this epitope in constitutively expressive animals has undergone significant mutation at the genomic level in humans. Pathological re-expression is presumed to require permissive changes at a cellular level. Detailing these alterations is a prerequisite to the comprehension of the metastatic phenotype. In this context, the possibility of therapeutic strategies affecting alpha gal expression are also discussed.","title":"A possible role for the alpha 1-->3 galactosyl epitope and the natural anti-gal antibody in oncogenesis."},{"docid":"MED-3276","text":"Methionine is an essential amino acid with many key roles in mammalian metabolism such as protein synthesis, methylation of DNA and polyamine synthesis. Restriction of methionine may be an important strategy in cancer growth control particularly in cancers that exhibit dependence on methionine for survival and proliferation. Methionine dependence in cancer may be due to one or a combination of deletions, polymorphisms or alterations in expression of genes in the methionine de novo and salvage pathways. Cancer cells with these defects are unable to regenerate methionine via these pathways. Defects in the metabolism of folate may also contribute to the methionine dependence phenotype in cancer. Selective killing of methionine dependent cancer cells in co-culture with normal cells has been demonstrated using culture media deficient in methionine. Several animal studies utilizing a methionine restricted diet have reported inhibition of cancer growth and extension of a healthy life-span. In humans, vegan diets, which can be low in methionine, may prove to be a useful nutritional strategy in cancer growth control. The development of methioninase which depletes circulating levels of methionine may be another useful strategy in limiting cancer growth. The application of nutritional methionine restriction and methioninase in combination with chemotherapeutic regimens is the current focus of clinical studies. Copyright © 2012 Elsevier Ltd. All rights reserved.","title":"A review of methionine dependency and the role of methionine restriction in cancer growth control and life-span extension."},{"docid":"MED-3292","text":"The human APOBEC3G protein is an innate anti-viral factor that can dominantly inhibit the replication of some endogenous and exogenous retroviruses. The prospects of purposefully harnessing such an anti-viral defense are under investigation. Here, long-term co-culture experiments were used to show that porcine endogenous retrovirus (PERV) transmission from pig to human cells is reduced to nearly undetectable levels by expressing human APOBEC3G in virus-producing pig kidney cells. Inhibition occurred by a deamination-independent mechanism, likely after particle production but before the virus could immortalize by integration into human genomic DNA. PERV inhibition did not require the DNA cytosine deaminase activity of APOBEC3G and, correspondingly, APOBEC3G-attributable hypermutations were not detected. In contrast, over-expression of the sole endogenous APOBEC3 protein of pigs failed to interfere significantly with PERV transmission. Together, these data constitute the first proof-of-principle demonstration that APOBEC3 proteins can be used to fortify the innate anti-viral defenses of cells to prevent the zoonotic transmission of an endogenous retrovirus. These studies suggest that human APOBEC3G-transgenic pigs will provide safer, PERV-less xenotransplantation resources and that analogous cross-species APOBEC3-dependent restriction strategies may be useful for thwarting other endogenous as well as exogenous retrovirus infections.","title":"The Restriction of Zoonotic PERV Transmission by Human APOBEC3G"},{"docid":"MED-3310","text":"We observed five consecutive cases of Hypersensitivity Pneumonitis in subjects working in a salami factory. The workers had to clean the white mould growing on salami surface using a manual wire brush. The five patients (four female) had a mean age of 39 +/- 15 years; two were smokers. Three patients had an acute clinical presentation with fever, dyspnoea, dry cough, oxygen desaturation, and presented at the emergency department with suspected diagnosis of community acquired pneumonia. The mean latency for developing respiratory symptoms was 11.6 days. Pulmonary function test demonstrated a reduction in diffusing capacity (DLCO) in all 5 patients (60 +/- 15% of predicted value). Skin prick test was positive for Penicillium spp in 3 cases and for Cladosporium and Aspergillus spp in 2 others. Specific IgG antibodies against Penicillium spp were positive in 3 subjects; 2 were positive for Aspergillus Fumigatus. The prevailing radiological pattern was a ground glass appearance in the three patients with acute clinical onset and a centrilobular one in patients with subacute onset. All patients were advised to avoid exposure to the antigens. Follow-up visits including pulmonary function testing, and DLCO measurement were conducted at one, three and six months. HRCT was performed at six month. Four subjects had a complete radiological and clinical resolution after changing work. Only one patient was treated with oral steroids for severe dyspnoea and progressive reduction of DLCO, gaining a complete radiological and clinical stability at six months.","title":"A new type of Hypersensitivity Pneumonitis: salami brusher's disease."},{"docid":"MED-1617","text":"Background Dietary modification via caloric restriction is associated with multiple effects related to improved metabolic and cardiovascular health. However, a mandated reduction in kilocalories is not well-tolerated by many individuals, limiting the long-term application of such a plan. The Daniel Fast is a widely utilized fast based on the Biblical book of Daniel. It involves a 21 day ad libitum food intake period, devoid of animal products and preservatives, and inclusive of fruits, vegetables, whole grains, legumes, nuts, and seeds. The purpose of the present study was to determine the efficacy of the Daniel Fast to improve markers of metabolic and cardiovascular disease risk. Methods 43 subjects (13 men; 30 women; 35 ± 1 yrs; range: 20-62 yrs) completed a 21 day period of modified food intake in accordance with detailed guidelines provided by investigators. All subjects purchased and prepared their own food. Following initial screening, subjects were given one week to prepare for the fast, after which time they reported to the lab for their pre-intervention assessment (day 1). After the 21 day fast, subjects reported to the lab for their post-intervention assessment (day 22). For both visits, subjects reported in a 12 hr fasted state, performing no strenuous physical activity during the preceding 24-48 hrs. At each visit, mental and physical health (SF-12 form), resting heart rate and blood pressure, and anthropometric variables were measured. Blood was collected for determination of complete blood count, metabolic panel, lipid panel, insulin, HOMA-IR, and C-reactive protein (CRP). Subjects' self-reported compliance, mood, and satiety in relation to the fast were also recorded. Diet records were maintained by all subjects during the 7 day period immediately prior to the fast (usual intake) and during the final 7 days of the fast. Results Subjects' compliance to the fast was 98.7 ± 0.2% (mean ± SEM). Using a 10 point scale, subjects' mood and satiety were both 7.9 ± 0.2. The following variables were significantly (p < 0.05) lower following the fast as compared to before the fast: white blood cell count (5.68 ± 0.24 vs. 4.99 ± 0.19 103·μL-1), blood urea nitrogen (13.07 ± 0.58 vs. 10.14 ± 0.59 mg·dL-1), blood urea nitrogen/creatinine (14.74 ± 0.59 vs. 11.67 ± 0.68), protein (6.95 ± 0.07 vs. 6.77 ± 0.06 g·dL-1), total cholesterol (171.07 ± 4.57 vs. 138.69 ± 4.39 mg·dL-1), LDL-C (98.38 ± 3.89 vs. 76.07 ± 3.53 mg·dL-1), HDL-C (55.65 ± 2.50 vs. 47.58 ± 2.19 mg·dL-1), SBP (114.65 ± 2.34 vs. 105.93 ± 2.12 mmHg), and DBP (72.23 ± 1.59 vs. 67.00 ± 1.43 mmHg). Insulin (4.42 ± 0.52 vs. 3.37 ± 0.35 μU·mL-1; p = 0.10), HOMA-IR (0.97 ± 0.13 vs.0.72 ± 0.08; p = 0.10), and CRP (3.15 ± 0.91 vs. 1.60 ± 0.42 mg·L-1; p = 0.13), were lowered to a clinically meaningful, albeit statistically insignificant extent. No significant difference was noted for any anthropometric variable (p > 0.05). As expected, multiple differences in dietary intake were noted (p < 0.05), including a reduction in total kilocalorie intake (2185 ± 94 vs. 1722 ± 85). Conclusion A 21 day period of modified dietary intake in accordance with the Daniel Fast is 1) well-tolerated by men and women and 2) improves several risk factors for metabolic and cardiovascular disease. Larger scale, randomized studies, inclusive of a longer time period and possibly a slight modification in food choice in an attempt to maintain HDL cholesterol, are needed to extend these findings.","title":"Effect of a 21 day Daniel Fast on metabolic and cardiovascular disease risk factors in men and women"},{"docid":"MED-3932","text":"Background Caffeine consumption has been associated with a reduced risk of Parkinson disease. The association is strong and consistent in men, but uncertain in women, possibly because of an interaction with hormone replacement therapy. We sought to confirm these findings using data on Parkinson disease incidence in the CPS II Nutrition Cohort, a large prospective study of men and women. Methods We conducted a prospective study of caffeine intake and risk of PD within the Cancer Prevention Study II Nutrition Cohort. Intakes of coffee and other sources of caffeine were assessed at baseline. Incident cases of PD (n = 317; 197 men and 120 women) were confirmed by treating physicians and medical record review. Relative risks (RR) were estimated using proportional hazards models, adjusting for age, smoking and alcohol consumption. Results After adjustment for age, smoking and alcohol intake, high caffeine consumption was associated with a reduced risk of PD. The relative risk comparing the 5th to the 1st quintile of caffeine intake was 0.43 (CI: 0.26, 0.71, p-trend = <0.002) in men, and 0.61 (95% CI: 0.34, 1.09; p for trend =0.05) in women. Among women, this association was stronger among never users of hormone replacement therapy (RR=0.32) than among ever users (RR=0.81, p-interaction = 0.15). Consumption of decaffeinated coffee was not associated with PD risk. Conclusion Findings from this large prospective study of men and women are consistent with a protective effect of caffeine intake on PD incidence, with an attenuating influence of hormone replacement therapy in women.","title":"Caffeine and risk of Parkinson disease in a large cohort of men and women"},{"docid":"MED-2359","text":"INTRODUCTION: ALPHA-GAL is a glycoconjugate present on cell membranes of mammals and bacteria but not humans who display anti-Gal antibodies (AB) in high titers provoked by the commensal gut flora. In the present study, we sought to determine the longitudinal course of alpha-Gal specific AB titers of all isotypes over 8 weeks among healthy adult subjects. Furthermore, we hypothesized that inflammatory bowel disease (IBD) patients display increased anti-Gal titers. MATERIALS AND METHODS: We drew serum from healthy probands (n=20) weekly for 8 weeks and obtained plasma samples of from patients suffering from Crohn's disease (n=20) and ulcerative colitis (n=20). We measured anti-Gal ABs of all isotypes and total immunoglobulin (Ig) content using an enzyme-linked immunosorbent assay technique. For statistical evaluation of the longitudinal titers, we calculated confidence intervals for the slopes of a random intercept model, comparing variances between and within the probands. For group comparisons, we performed paired student t-tests and Pearson correlations. RESULTS: Alpha-Gal specific IgG, IgM, IgD, and IgA titers remained unvaried within a narrow range upon longitudinal observation. Most probands did not display alpha-Gal specific IgE ABs. Crohn's disease patients showed highly increased alpha-Gal-specific IgA titers compared with control subjects (P<.01). CONCLUSION: Apart from IgE, alpha-Gal-specific ABs of all isotypes remained constant over longer time periods in healthy subjects. Thus, significant titer changes actually represent increased antigen exposure and a specific anti-alpha-Gal response. Crohn's disease patients display increased anti-Gal IgA titers compared with healthy controls, which reflects a chronically impaired mucosal gut barrier in this patient cohort. Copyright © 2011 Elsevier Inc. All rights reserved.","title":"Anti-Gal titers in healthy adults and inflammatory bowel disease patients."},{"docid":"MED-2587","text":"Recent research has demonstrated that successful simultaneous treatment of multiple risk factors including cholesterol, triglycerides, homocysteine, lipoprotein (a) [Lp(a)], fibrinogen, antioxidants, endothelial dysfunction, inflammation, infection, and dietary factors can lead to the regression of coronary artery disease and the recovery of viable myocardium. However, preliminary work revealed that a number of individuals enrolled in the original study went on popular high-protein diets in an effort to lose weight. Despite increasing numbers of individuals following high-protein diets, little or no information is currently available regarding the effect of these diets on coronary artery disease and coronary blood flow. Twenty-six people were studied for 1 year by using myocardial perfusion imaging (MPI), echocardiography (ECHO), and serial blood work to evaluate the extent of changes in regional coronary blood flow, regional wall motion abnormalities, and several independent variables known to be important in the development and progression of coronary artery disease. Treatment was based on homocysteine, Lp (a), C-reactive protein (C-RP), triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and fibrinogen levels. Each variable was independently treated as previously reported. MPI and ECHO were performed at the beginning and end of the study for each individual. The 16 people (treatment group/TG) studied modified their dietary intake as instructed. Ten additional individuals elected a different dietary regimen consisting of a \"high-protein\" (high protein group/HPG) diet, which they believed would \"improve\" their overall health. Patients in the TG demonstrated a reduction in each of the independent variables studied with regression in both the extent and severity of coronary artery disease (CAD) as quantitatively measured by MPI. Recovery of viable myocardium was seen in 43.75% of myocardial segments in these patients, documented with both MPI and ECHO evaluations. Individuals in the HPG showed worsening of their independent variables. Most notably, fibrinogen, Lp (a), and C-RP increased by an average of 14%, 106%, and 61% respectively. Progression of the extent and severity of CAD was documented in each of the vascular territories with an overall cumulative progression of 39.7%. The differences between progression and extension of disease in the HPG and the regression of disease in the TG were statistically (p<0.001) significant. Patients following recommended treatment for each of the independent variables were able to regress both the extent and severity of their coronary artery disease (CAD), as well as improve their myocardial wall motion (function) while following the prescribed medical and dietary guidelines. However, individuals receiving the same medical treatment but following a high-protein diet showed a worsening of independent risk factors, in addition to progression of CAD. These results would suggest that high-protein diets may precipitate progression of CAI) through increases in lipid deposition and inflammatory and coagulation pathways.","title":"The effect of high-protein diets on coronary blood flow."},{"docid":"MED-1249","text":"The effect of dietary protein on the level of plasma cholesterol in young, healthy, normolipidemic women was investigated in two separate studies by feeding either a conventional diet containing mixed protein, or a plant protein diet in which the animal protein of the first diet was replaced by soy protein meat analogues and soy milk. The diets were similar with respect to carbohydrate, fat and sterol composition. The first study, lasting 73 days and involving six subjects, gave an indication that plasma cholesterol levels were lower on the plant protein diet. The second study, which incorporated a number of improvements based on experience, lasted 78 days and used a cross-over design involving two groups of five subjects each. In this study, the mean plasma cholesterol level was found to be significantly lower on the plant protein diet.","title":"Hypocholesterolemic effect of substituting soybean protein for animal protein in the diet of healthy young women."},{"docid":"MED-4164","text":"PURPOSE OF REVIEW: This review discusses recent evidence that suggests a significant underestimation of protein requirements in adult humans. RECENT FINDINGS: Traditionally, total protein requirements for humans have been determined using nitrogen balance. The recent Dietary Reference Intake recommendations for mean and population-safe intakes of 0.66 and 0.8 g/kg/day, respectively, of high-quality protein in adult humans are based on a meta-analysis of nitrogen balance studies using single linear regression analysis. We reanalyzed existing nitrogen balance studies using two-phase linear regression analysis and obtained mean and safe protein requirements of 0.91 and 0.99 g/kg/day, respectively. The two-phase linear regression analysis is considered more appropriate for biological analysis of dose-response curves. Considering the inherent problems associated with the nitrogen balance method, we developed an alternative method, the indicator amino acid oxidation technique, to determine protein requirements The mean and population-safe requirements in adult men were determined to be 0.93 and 1.2 g/kg/day and are 41 and 50%, respectively, higher than the current Dietary Reference Intakes recommendations. SUMMARY: The indicator amino acid oxidation-based requirement values of 0.93 and 1.2 g protein/kg/day and the reanalysis of existing nitrogen balance studies are significantly higher than current recommendations. Therefore, there is an urgent need to reassess recommendations for protein intake in adult humans.","title":"Evidence that protein requirements have been significantly underestimated."},{"docid":"MED-2355","text":"Anaphylaxis is a severe allergic reaction that can be rapidly progressing and fatal. In instances where the triggering allergen is not known, establishing the etiology of anaphylaxis is pivotal to long-term risk management. Our recent work has identified a novel IgE antibody (Ab) response to a mammalian oligosaccharide epitope, galactose-alpha-1,3-galactose (alpha-gal), that has been associated with two distinct forms of anaphylaxis: (1) immediate onset anaphylaxis during first exposure to intravenous cetuximab, and (2) delayed onset anaphylaxis 3–6 h after ingestion of mammalian food products (e.g., beef and pork). The results of our studies strongly suggest that tick bites are a cause, if not the only significant cause, of IgE Ab responses to alpha-gal in the southern, eastern and central United States. Patients with IgE Ab to alpha-gal continue to emerge and, increasingly, these cases involve children. This IgE Ab response cross-reacts with cat and dog but does not appear to pose a risk for asthma; however, it may impair diagnostic testing in some situations.","title":"Delayed Anaphylaxis to Red Meat in Patients with IgE Specific for Galactose alpha-1,3-Galactose (alpha-gal)"},{"docid":"MED-3875","text":"BACKGROUND: Mammalian lignans, enterolactone (EL) and enterodiol (ED), have been shown to inhibit breast and colon carcinoma. To date, there have been no reports of the effect of lignans on prostatic carcinoma. We investigated the effects of ED and EL on three human prostate cancer cell lines (PC-3, DU-145 and LNCaP). MATERIALS AND METHODS: Cells were treated with either 0.1% (v/v) DMSO (vehicle) or 10-100 microM of EL, ED or genistein (positive control) for 72 hours. Cell viability was measured by the propidium iodide nuclei staining fluorometric assay with each assay performed in triplicate. RESULTS: At 10-100 microM, EL significantly inhibited the growth of all cell lines, whereas ED only inhibited PC-3 and LNCaP cells. While EL was a more potent growth inhibitor than ED, both were less potent than genistein. The dose for 50% growth inhibition of LNCaP cells (IC50) by EL was 57 microM, whereas IC50 was 100 microM for ED, (the observed IC50 for genistein was 25 microM). CONCLUSION: ED and EL suppress the growth of prostate cancer cells, and may do so via hormonally-dependent and independent mechanisms.","title":"Effect of mammalian lignans on the growth of prostate cancer cell lines."},{"docid":"MED-3926","text":"Sixteen parkinsonian patients with daily fluctuations in the clinical response to levodopa have been placed on a redistribution protein diet. The diet was virtually protein-free until the evening meal and then unrestricted until bedtime. While on the redistribution protein diet, a group of patients (5 out of 16) had a clear and significant benefit from dietary therapy showing a definite reduction of diurnal motor performance fluctuations. In addition, all patients tended to show an improvement and a more constant response to levodopa treatment. A trial of redistribution protein diet appears a simple, reasonable, worthwhile approach to PD patients who begin to experience oscillating clinical response to levodopa treatment.","title":"Protein redistribution diet and antiparkinsonian response to levodopa."},{"docid":"MED-2590","text":"Nineteen people without prior history of documented heart disease were studied for 8 months to determine the effect of treatment based on an immunologic unified theory of vascular disease. Subjects underwent myocardial perfusion imaging to quantify the extent and severity of coronary artery disease, along with assessment of wall motion abnormalities and ejection fraction by both nuclear and echocardiographic methods. These tests were repeated at the end of the study. Treatment consisted of dietary changes, treatment of cholesterol, triglycerides, homocysteine, lipoprotein (a), fibrinogen, C-reactive protein, and infection. Patients who followed the dietary recommendations demonstrated statistically reduced disease in all three major coronary arteries, whereas those individuals who followed high-protein diets demonstrated statistically greater levels of disease.","title":"Reversing heart disease in the new millennium--the Fleming unified theory."},{"docid":"MED-3955","text":"BACKGROUND Polybrominated Diphenyl Ethers (PBDEs), widely used as flame retardants since the 1970s, have exhibited endocrine disruption in experimental studies. Tetra- to hexa-BDE congeners are estrogenic, while hepta-BDE and 6-OH-BDE-47 are antiestrogenic. Most PBDEs also have antiandrogenic activity. It is not clear, however, whether PBDEs affect human reproduction. OBJECTIVES The analysis was designed to investigate the potential endocrine disruption of PBDEs on the age at menarche in adolescent girls. METHODS We analyzed the data from a sample of 271 adolescent girls (age 12–19 years) in the National Health and Nutrition Examination Survey (NHANES), 2003–2004. We estimated the associations between individual and total serum BDEs (BDE-28, -47, -99, -100, -153, and -154, lipid adjusted) and mean age at menarche. We also calculated the risk ratios (RRs) and 95% confidence intervals (CI) for menarche prior to age 12 years in relation to PBDE exposure. RESULTS The median total serum BDE concentration was 44.7 ng/g lipid. Higher serum PBDE concentrations were associated with slightly earlier ages at menarche. Each natural log unit of total BDEs was related to a change of −0.10 (95% CI: −0.33, 0.13) years of age at menarche and a RR of 1.60 (95% CI: 1.12, 2.28) for experiencing menarche before 12 years of age, after adjustment for potential confounders. CONCLUSION These data suggest high concentrations of serum PBDEs during adolescence are associated with a younger age of menarche.","title":"Serum PBDEs and Age at Menarche in Adolescent Girls: Analysis of the National Health and Nutrition Examination Survey 2003–2004"},{"docid":"MED-3270","text":"Aging affects all organisms and its basic mechanisms are expected to be conserved across species. Oxidation of proteins has been proposed to be one of the basic mechanisms linking oxygen radicals with the basic aging process. If oxidative damage to proteins is involved in aging, long-lived animals (which age slowly) should show lower levels of markers of this kind of damage than short-lived ones. However, this possibility has not been investigated yet. In this study, steady-state levels of markers of different kinds of protein damage--oxidation (glutamic and aminoadipic semialdehydes), mixed glyco- and lipoxidation (carboxymethyl- and carboxyethyllysine), lipoxidation (malondialdehydelysine) and amino acid composition--were measured in the heart of eight mammalian species ranging in maximum life span (MLSP) from 3.5 to 46 years. Oxidation markers were directly correlated with MLSP across species. Mixed glyco- and lipoxidation markers did not correlate with MLSP. However, the lipoxidation marker malondialdehydelysine was inversely correlated with MLSP (r2=0.85; P<0.001). The amino acid compositional analysis revealed that methionine is the only amino acid strongly correlated MLSP and that such correlation is negative (r2=0.93; P<0.001). This trait may contribute to lower steady-state levels of oxidized methionine residues in cellular proteins. These results reinforce the notion that high longevity in homeothermic vertebrates is achieved in part by constitutively decreasing the sensitivity of both tissue proteins and lipids to oxidative damage. This is obtained by modifying the constituent structural components of proteins and lipids, selecting those less sensitive to oxidative modifications.","title":"Protein methionine content and MDA-lysine adducts are inversely related to maximum life span in the heart of mammals."},{"docid":"MED-2999","text":"Many of the commonest diseases in the economically more developed communities are characteristic of modern Western culture. Evidence is presented suggesting that they represent a failure of adaptation to the dramatic changes in diet that have been associated with the emergence of modern Western culture. Dietary changes aimed at the alleviation and prevention of these diseases are discussed and recommended.","title":"Western diseases and their emergence related to diet."},{"docid":"MED-4037","text":"In the present study, 21 polycyclic aromatic hydrocarbon (PAH) congeners were measured in the exhaust stack of 3 types of restaurants: 9 Chinese, 7 Western, and 4 barbeque (BBQ). The total PAH concentration of BBQ restaurants (58.81 ± 23.89 μg m(-3)) was significantly higher than that of Chinese (20.99 ± 13.67 μg m(-3)) and Western (21.47 ± 11.44 μg m(-3)) restaurants. The total benzo[a]pyrene potency equivalent (B[a]P(eq)) concentrations, however, were highest in Chinese restaurants (1.82 ± 2.24 μg m(-3)), followed by Western (0.86 ± 1.43 μg m(-3), p<0.01) and BBQ-type restaurants (0.59 ± 0.55 μg m(-3), p<0.01). We further developed a probabilistic risk model to assess the incremental lifetime cancer risk (ILCR) for people exposed to carcinogenic PAHs. Because the exhaust stack directly affected the back-door neighbors of these restaurants, we were concerned with the real exposure of groups near the exhaust stack outlets of these restaurants. The ILCRs for total exposure of the neighbors (inhalation+dermal contact+ingestion) were 2.6-31.3, 1.5-14.8, and 1.3-12.2 × 10(-6) in Chinese, Western, and BBQ restaurants, respectively. We suggest that the maximum acceptable exposure time to the exhaust stack outlet area for Chinese, Western, and BBQ restaurants ranges between 5-19, 17-42, and 18-56 h month(-1), respectively, based on an ILCR of less than 10(-6). Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.","title":"Carcinogenic potencies of polycyclic aromatic hydrocarbons for back-door neighbors of restaurants with cooking emissions."},{"docid":"MED-2369","text":"Background Carbohydrate moieties are frequently encountered in food and can elicit IgE responses, the clinical significance of which has been unclear. Recent work, however, has shown that IgE antibodies to galactose-α-1,3-galactose (α-gal), a carbohydrate commonly expressed on nonprimate mammalian proteins, are capable of eliciting serious, even fatal, reactions. Objective We sought to determine whether IgE antibodies to α-gal are present in sera from patients who report anaphylaxis or urticaria after eating beef, pork, or lamb. Methods Detailed histories were taken from patients presenting to the University of Virginia Allergy Clinic. Skin prick tests (SPTs), intradermal skin tests, and serum IgE antibody analysis were performed for common indoor, outdoor, and food allergens. Results Twenty-four patients with IgE antibodies to α-gal were identified. These patients described a similar history of anaphylaxis or urticaria 3 to 6 hours after the ingestion of meat and reported fewer or no episodes when following an avoidance diet. SPTs to mammalian meat produced wheals of usually less than 4 mm, whereas intradermal or fresh-food SPTs provided larger and more consistent wheal responses. CAP-RAST testing revealed specific IgE antibodies to beef, pork, lamb, cow’s milk, cat, and dog but not turkey, chicken, or fish. Absorption experiments indicated that this pattern of sensitivity was explained by an IgE antibody specific for α-gal. Conclusion We report a novel and severe food allergy related to IgE antibodies to the carbohydrate epitope α-gal. These patients experience delayed symptoms of anaphylaxis, angioedema, or urticaria associated with eating beef, pork, or lamb.","title":"Delayed anaphylaxis, angioedema, or urticaria after consumption of red meat in patients with IgE antibodies specific for galactose-α-1,3-galactose"},{"docid":"MED-1620","text":"Background The Daniel Fast is a vegan diet that prohibits the consumption of animal products, refined foods, white flour, preservatives, additives, sweeteners, flavorings, caffeine, and alcohol. Following this dietary plan for 21 days has been demonstrated to improve blood pressure, LDL-C, and certain markers of oxidative stress, but it has also been shown to lower HDL-C. Krill oil supplementation has been shown to increase HDL-C. Methods We investigated the effects of following a Daniel Fast dietary plan with either krill oil supplementation (2 g/day) or placebo supplementation (coconut oil; 2 g/day) for 21 days. The subjects in this study (12 men and 27 women) were heterogeneous with respect to body mass index (BMI) (normal weight, overweight, and obese), blood lipids (normolipidemic and hyperlipidemic), blood glucose (normal fasting glucose, impaired fasting glucose, and type 2 diabetic), and blood pressure (normotensive and hypertensive). Results Krill oil supplementation had no effect on any outcome measure (all p > 0.05), and so the data from the krill oil group and the placebo group were collapsed and analyzed to examine the effects of following a 21-day Daniel Fast. Significant reductions were observed in LDL-C (100.6 ± 4.3 mg/dL vs. 80.0 ± 3.7 mg/dL), the LDL:HDL ratio (2.0 ± 0.1 vs. 1.7 ± 0.1), fasting blood glucose (101.4 ± 7.5 mg/dL vs. 91.7 ± 3.4 mg/dL), fasting blood insulin (7.92 ± 0.80 μU/mL vs. 5.76 ± 0.59 μU/mL), homeostasis model assessment of insulin resistance (HOMA-IR) (2.06 ± 0.30 vs. 1.40 ± 0.21), systolic BP (110.7 ± 2.2 mm Hg vs. 105.5 ± 1.7 mm Hg), and body weight (74.1 ± 2.4 kg vs. 71.5 ± 2.3 kg) (all p < 0.05). Conclusion Following a Daniel Fast dietary plan improves a variety of cardiometabolic parameters in a wide range of individuals in as little as 21 days, and these improvements are unaffected by krill oil supplementation. Trial registration Clinicaltrial.govNCT01378767","title":"A 21-day Daniel fast with or without krill oil supplementation improves anthropometric parameters and the cardiometabolic profile in men and women"},{"docid":"MED-3142","text":"AIM: Soy foods are the major source of isoflavones, which are believed to play important roles in genesis of breast cancer and its progression. We here conducted a prospective study to evaluate the association of soy isoflavone food consumption with breast cancer prognosis. METHODS: A prospective study was performed from January 2004 and January 2006 in China. Trained interviewers conducted face-to-face interviews using a structured questionnaire to collect information on dietary habits and potential confounding factors. The relative risk [hazard ratio (HR)] and 95% CI were calculated from the Cox regression model for all significant predictors from cancer diagnosis to the endpoint of the study (event). RESULTS: After a median follow up of 52.1 months (range, 9-60 months), a total of 79 breast cancer related deaths were recorded in our study, risk being inversely associated with a high intake of soy isoflavone. With an average intake of soy isoflavone above 17.3 mg/day, the mortality of breast cancer can be reduced by about 38-36%. We also found the decreased breast cancer death with high soy protein intake, with a HR (95% CI) of 0.71 (0.52-0.98). Stratified analysis with reference to the ER status, further demonstrated a better prognosis of ER positive breast cancer with a high intake of soy isoflavone (HR 0.59, 0.40-0.93). CONCLUSION: Our study shows the soy food intake is associated with longer survival and low recurrence among breast cancer patients. A cohort study with a larger sample size and long term follow-up is now needed.","title":"Positive effects of soy isoflavone food on survival of breast cancer patients in China."},{"docid":"MED-1188","text":"One hundred and eighteen missionaries working on 75 mission stations or hospitals in 24 sub-Saharan African countries provided information about their medical practice in the preceding year of 1981. Details were collected of the total number of patients seen and admitted during the year, and the number of cases of bloody diarrhoea, typhoid and inflammatory bowel disease. Over 1 million outpatients and about 190,000 inpatients were treated. These included 12,859 cases of bloody diarrhoea, of whom 1,914 had typhoid. Twenty-two cases of inflammatory bowel disease were also reported. Histological support was least available in West Africa and only 25% of hospitals had access to this facility. Nevertheless, the frequency with which inflammatory bowel disease in sub-Saharan Africa is difficult and limited by access to diagnostic facilities. It is likely to be some time before reliable estimates of the incidence and prevalence of Crohn's disease and ulcerative colitis in the rural African population can be made.","title":"Inflammatory bowel disease in rural sub-Saharan Africa: rarity of diagnosis in patients attending mission hospitals."},{"docid":"MED-1712","text":"Diet contributes to over one-third of cancer deaths in the Western world, yet the factors in the diet that influence cancer are not elucidated. A reduction in caloric intake dramatically slows cancer progression in rodents, and this may be a major contribution to dietary effects on cancer. Insulin-like growth factor I (IGF-I) is lowered during dietary restriction (DR) in both humans and rats. Because IGF-I modulates cell proliferation, apoptosis, and tumorigenesis, the mechanisms behind the protective effects of DR may depend on the reduction of this multifaceted growth factor. To test this hypothesis, IGF-I was restored during DR to ascertain if lowering of IGF-I was central to slowing bladder cancer progression during DR. Heterozygous p53-deficient mice received a bladder carcinogen, p-cresidine, to induce preneoplasia. After confirmation of bladder urothelial preneoplasia, the mice were divided into three groups: (a) ad libitum; (b) 20% DR; and (c) 20% DR plus IGF-I (IGF-I/DR). Serum IGF-I was lowered 24% by DR but was completely restored in the IGF-I/DR-treated mice using recombinant IGF-I administered via osmotic minipumps. Although tumor progression was decreased by DR, restoration of IGF-I serum levels in DR-treated mice increased the stage of the cancers. Furthermore, IGF-I modulated tumor progression independent of changes in body weight. Rates of apoptosis in the preneoplastic lesions were 10 times higher in DR-treated mice compared to those in IGF/DR- and ad libitum-treated mice. Administration of IGF-I to DR-treated mice also stimulated cell proliferation 6-fold in hyperplastic foci. In conclusion, DR lowered IGF-I levels, thereby favoring apoptosis over cell proliferation and ultimately slowing tumor progression. This is the first mechanistic study demonstrating that IGF-I supplementation abrogates the protective effect of DR on neoplastic progression.","title":"Dietary restriction reduces insulin-like growth factor I levels, which modulates apoptosis, cell proliferation, and tumor progression in p53-defici..."},{"docid":"MED-2482","text":"Previous studies have suggested that probiotic administration may have therapeutic and/or preventive effects on atopic dermatitis in infants; however, its role in allergic airway diseases remains controversial. To determine whether daily supplementation with specific Lactobacillus gasseri A5 for 8 weeks can improve the clinical symptoms and immunoregulatory changes in school children suffering from asthma and allergic rhinitis (AR). We conducted a randomized, double-blind, placebo-controlled study on school children (age, 6-12 years) with asthma and AR. The eligible study subjects received either L. gasseri A5 (n = 49) or a placebo (n = 56) daily for 2 months. Pulmonary function tests were performed, and the clinical severity of asthma and AR was evaluated by the attending physicians in the study period. Diary cards with records of the day- and nighttime peak expiratory flow rates (PEFR), symptoms of asthma, and AR scores of the patients were used for measuring the outcome of the treatment. Immunological parameters such as the total IgE and cytokine production by the peripheral blood mononuclear cells (PBMCs) were determined before and after the probiotic treatments. Our results showed the pulmonary function and PEFR increased significantly, and the clinical symptom scores for asthma and AR decreased in the probiotic-treated patients as compared to the controls. Further, there was a significant reduction in the TNF-α, IFN-γ, IL-12, and IL-13 production by the PBMCs following the probiotic treatment. In conclusion, probiotic supplementation may have clinical benefits for school children suffering from allergic airway diseases such as asthma and AR.","title":"Randomized placebo-controlled trial of lactobacillus on asthmatic children with allergic rhinitis."},{"docid":"MED-2206","text":"Sweet potato is one of the crops selected for NASA's Advanced Life Support Program for potential long-duration lunar/Mars missions. This article presents recipes of products made from sweet potato and determines the consumer acceptability of products containing from 6% to 20% sweet potato on a dry weight basis. These products were developed for use in nutritious and palatable meals for future space explorers. Sensory evaluation (appearance/color, aroma, texture, flavor/taste, and overall acceptability) studies were conducted to determine the consumer acceptability of vegetarian products made with sweet potato using panelists at NASA/Johnson Space Center in Houston, TX. None of these products including the controls, contained any ingredient of animal origin with the exception of sweet potato pie. A 9-point hedonic scale (9 being like extremely and 1 being dislike extremely) was used to evaluate 10 products and compare them to similar commercially available products used as controls. The products tested were pancakes, waffles, tortillas, bread, pie, pound cake, pasta, vegetable patties, doughnuts, and pretzels. All of the products were either liked moderately or liked slightly with the exception of the sweet potato vegetable patties, which were neither liked nor disliked. Mean comparisons of sensory scores of sweet potato recipes and their controls were accomplished by using the Student t-test. Because of their nutritional adequacy and consumer acceptability, these products are being recommended to NASA's Advanced Life Support Program for inclusion in a vegetarian menu plan designed for lunar/Mars space missions.","title":"Consumer acceptance of vegetarian sweet potato products intended for space missions."},{"docid":"MED-2449","text":"BACKGROUND: Recently, some common foods in daily life have been found to have anti-allergic effects. We have reported that tomato extract (TE) could possibly inhibit histamine release and mouse ear-swelling responses. Moreover, it is reported that TE could relieve the symptoms for Japanese cedar pollinosis. METHODS: To evaluate the anti-allergic effect of TE, we performed a randomized, double-blind, placebo-controlled study in 33 patients with perennial allergic rhinitis (PAR) using oral administration of TE (360 mg per day) or placebo for 8 weeks. RESULTS: We found that the sneezing score significantly decreased in the TE group at the end of the trial compared to the beginning (P < 0.05). There were decreasing tendencies of rhinorrhea and nasal obstruction in the TE group. The patients' quality of life was significantly improved in the TE group after 8 weeks of treatment (P < 0.05), but not in placebo group. A significant improvement in total symptom scores, combining sneezing, rhinorrhea and nasal obstruction, was observed after oral administration of TE for 8 weeks (P < 0.01). The safety of TE treatment was confirmed by laboratory tests and inspection of general conditions. CONCLUSIONS: TE can be expected to safely improve the nasal symptoms of PAR.","title":"An evaluation of the clinical efficacy of tomato extract for perennial allergic rhinitis."},{"docid":"MED-4514","text":"Background Data on the long-term association between low-carbohydrate diets and mortality are sparse. Objective To examine the association of low-carbohydrate diets with mortality during 26 years of follow-up in women and 20 years in men. Design A prospective cohort study of women and men, followed from 1980 (women) or 1986 (men) until 2006. Low-carbohydrate diets, either animal-based (emphasizing animal sources of fat and protein), or vegetable-based (emphasizing vegetable sources of fat and protein) were computed from multiple validated food frequency questionnaire assessed during follow-up. Setting Nurses' Health Study and Health Professionals' Follow-up Study Participants 85,168 women (aged 34-59 years at baseline) and 44,548 men (aged 40-75 years at baseline) without heart disease, cancer, or diabetes. Measurement Investigator documented 12,555 deaths (2,458 cardiovascular, 5,780 cancer) in women and 8,678 deaths (2,746 cardiovascular, 2,960 cancer) in men. Results The overall low-carbohydrate score was associated with a modest increase in overall mortality in pooled analysis (Hazard Ratio, HR, comparing extreme deciles=1.12 (95% CI=1.01-1.24, p-trend=0.14). The animal low-carbohydrate score was associated with a higher all-cause mortality (pooled HR comparing extreme deciles=1.23, 95% CI=1.11-1.37, p-trend=0.05), cardiovascular mortality (corresponding HR=1.14, 95% CI=1.01-1.29, p-trend=0.029), and cancer mortality (corresponding HR=1.28, 95% CI 1.02-1.60, p for trend = 0.09). In contrast, a higher vegetable low-carbohydrate score was associated with lower all-cause (HR=0.80, 95% CI=0.75-0.85, p-trend<0.001) and cardiovascular mortality (HR=0.77, 95% CI=0.68-0.87, p-trend<0.001). Limitations Diet and lifestyle characteristics were assessed with some degree of error, however, sensitivity analyses indicated that results were not unlikely to be substantially affected by residual or confounding or an unmeasured confounder. In addition, participants were not a representative sample of the U.S. population. Conclusion A low-carbohydrate diet based on animal sources was associated with higher all-cause mortality in both men and women, whereas a vegetable-based low-carbohydrate diet was associated with lower all-cause and cardiovascular disease mortality rates. Primary funding source NIH grants CA87969, HL60712, and CA95589","title":"Low-carbohydrate diets and all-cause and cause-specific mortality: Two cohort Studies"},{"docid":"MED-5204","text":"It is generally accepted that carbohydrate fermentation results in beneficial effects for the host because of the generation of short chain fatty acids, whereas protein fermentation is considered detrimental for the host's health. Protein fermentation mainly occurs in the distal colon, when carbohydrates get depleted and results in the production of potentially toxic metabolites such as ammonia, amines, phenols and sulfides. However, the effectivity of these metabolites has been established mainly in in vitro studies. In addition, some important bowel diseases such as colorectal cancer (CRC) and ulcerative colitis appear most often in the distal colon, which is the primary site of protein fermentation. Finally, epidemiological studies revealed that diets rich in meat are associated with the prevalence of CRC, as is the case in Western society. Importantly, meat intake not only increases fermentation of proteins but also induces increased intake of fat, heme and heterocyclic amines, which may also play a role in the development of CRC. Despite these indications, the relationship between gut health and protein fermentation has not been thoroughly investigated. In this review, the existing evidence about the potential toxicity of protein fermentation from in vitro animal and human studies will be summarized. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.","title":"Relevance of protein fermentation to gut health."},{"docid":"MED-2294","text":"The number of studies comparing nutritional quality of restrictive diets is limited. Data on vegan subjects are especially lacking. It was the aim of the present study to compare the quality and the contributing components of vegan, vegetarian, semi-vegetarian, pesco-vegetarian and omnivorous diets. Dietary intake was estimated using a cross-sectional online survey with a 52-items food frequency questionnaire (FFQ). Healthy Eating Index 2010 (HEI-2010) and the Mediterranean Diet Score (MDS) were calculated as indicators for diet quality. After analysis of the diet questionnaire and the FFQ, 1475 participants were classified as vegans (n = 104), vegetarians (n = 573), semi-vegetarians (n = 498), pesco-vegetarians (n = 145), and omnivores (n = 155). The most restricted diet, i.e., the vegan diet, had the lowest total energy intake, better fat intake profile, lowest protein and highest dietary fiber intake in contrast to the omnivorous diet. Calcium intake was lowest for the vegans and below national dietary recommendations. The vegan diet received the highest index values and the omnivorous the lowest for HEI-2010 and MDS. Typical aspects of a vegan diet (high fruit and vegetable intake, low sodium intake, and low intake of saturated fat) contributed substantially to the total score, independent of the indexing system used. The score for the more prudent diets (vegetarians, semi-vegetarians and pesco-vegetarians) differed as a function of the used indexing system but they were mostly better in terms of nutrient quality than the omnivores.","title":"Comparison of Nutritional Quality of the Vegan, Vegetarian, Semi-Vegetarian, Pesco-Vegetarian and Omnivorous Diet"},{"docid":"MED-2335","text":"Xenohormesis is a biological principle that explains how environmentally stressed plants produce bioactive compounds that can confer stress resistance and survival benefits to animals that consume them. Animals can piggyback off products of plants' sophisticated stress response which has evolved as a result of their stationary lifestyle. Factors eliciting the plant stress response can judiciously be employed to maximize yield of health-promoting plant compounds. The xenohormetic plant compounds can, when ingested, improve longevity and fitness by activating the animal's cellular stress response and can be applied in drug discovery, drug production, and nutritional enhancement of diet.","title":"Xenohormesis: health benefits from an eon of plant stress response evolution"},{"docid":"MED-2351","text":"Anti-Gal is a natural Ab abundantly produced in humans. It interacts specifically with the carbohydrate epitope Gal alpha 1-3Gal beta 1-4GlcNAc-R (termed the alpha-galactosyl epitope). This epitope is expressed in large amounts on thyrocytes of nonprimate mammals, but not of humans. We have previously found that binding of anti-Gal to alpha-galactosyl epitopes on porcine thyrocytes results in stimulatory effects similar to those exerted by thyroid-stimulating hormone (thyrotropin). In the present study, we tested the hypothesis that anti-Gal may contribute to Graves' disease (GD) pathogenesis by stimulation of the thyrocytes of patients with this autoimmune disorder. Anti-Gal binding and stimulatory effects were assessed in primary thyrocyte cultures. Anti-Gal specifically bound to GD thyrocytes and induced an increase in cAMP synthesis, 125I uptake, and DNA synthesis in these cells. Furthermore, the stimulatory effects of autologous sera on GD thyrocytes were greatly reduced after specific depletion of anti-Gal from these sera. No binding and no stimulatory effects of anti-Gal were observed, however, with normal human thyrocytes and with thyrocytes from thyrotoxic patients who lack thyroid-stimulating Igs or thyrotropin binding inhibiting Igs. These in vitro stimulatory effects of anti-Gal on GD thyrocytes suggest that this natural Ab may contribute to the in vivo continuous stimulation of thyrocytes in GD patients. The possibility that anti-Gal may stimulate GD thyrocytes via interaction with aberrantly expressed alpha-galactosyl epitopes on the thyroid-stimulating hormone receptor is discussed.","title":"Specific stimulation of Graves' disease thyrocytes by the natural anti-Gal antibody from normal and autologous serum."},{"docid":"MED-3355","text":"OBJECTIVE: To evaluate the effects of a high-fat and low-fat diet on taste sensitivity to oleic acid (C18:1) in lean and overweight/obese (OW/OB) subjects. DESIGN: Randomized cross-over dietary intervention involving the consumption of a high-fat (>45% fat) and low-fat (<20% fat) diet, both consumed over a 4-week period. SUBJECTS: A total of 19 lean, mean age 33±13 years, mean body mass index (BMI) 23.2±2.2 kg m(-2) and 12 OW/OB, mean age 39.5±3 years, mean BMI 28±2.6 kg m(-2), subjects participated in the study, which measured taste thresholds for C18:1, fat perception and hedonic ratings for regular (RF) and lowered-fat (LF) foods before, and following consumption of a high- and low-fat diet. RESULTS: Consumption of the low-fat diet increased taste sensitivity to C18:1 among lean and OW/OB subjects (P<0.05) and increased the subjects ability to perceive small differences in the fat content of custard (P=0.05). Consumption of the high-fat diet significantly decreased taste sensitivity to C18:1 among lean subjects (P<0.05), with no change in sensitivity among OW/OB persons (P=0.609). The hedonic ratings for several RF and LF foods differed following the diets. CONCLUSION: Alterations in the fat content of the diet modulated taste sensitivity to C18:1 among lean subjects, which was increased following a 4-week period of fat restriction and attenuated following the high-fat diet. The failure of the high-fat diet to alter fatty acid taste thresholds among OW/OB subjects suggests that these individuals were 'adapted' to high-fat exposure, perhaps because of differences in habitual fat consumption. Taken together, these data suggest that excessive dietary fat attenuates nutrient sensing epithelia response in the oral cavity, which could be associated with changes in diet and weight status.","title":"Recent fat intake modulates fat taste sensitivity in lean and overweight subjects."},{"docid":"MED-4206","text":"Vegetarian diets are rich in antioxidant phytochemicals. However, they may not act as antioxidants in vivo, and yet still have important signaling and regulatory functions. Some may act as pro-oxidants, modulating cellular redox tone and oxidizing redox sensitive sites. In this review, evidence for health benefits of vegetarian diets is presented from different perspectives: epidemiological, biomarker, evolutionary, and public health, as well as antioxidant. From the perspective of molecular connections between diet and health, evidence of a role for plasma ascorbic acid as a biomarker for future disease risk is presented. Basic concepts of redox-based cell signaling are presented, and effects of antioxidant phytochemicals on signaling, especially via redox tone, sulfur switches and the Antioxidant Response Element (ARE), are explored. Sufficient scientific evidence exists for public health policy to promote a plant-rich diet for health promotion. This does not need to wait for science to provide all the answers as to why and how. However, action and interplay of dietary antioxidants in the nonequilibrium systems that control redox balance, cell signaling, and cell function provide rich ground for research to advance understanding of orthomolecular nutrition and provide science-based evidence to advance public health in our aging population.","title":"Vegetarian diets and public health: biomarker and redox connections."},{"docid":"MED-3772","text":"A clinical link exists between severe dehydration and cognitive performance. Using rapid and severe water loss induced either by intense exercise and/or heat stress, initial studies suggested there were alterations in short-term memory and cognitive function related to vision, but more recent studies have not all confirmed these data. Some studies argue that water loss is not responsible for the observations made, and studies compensating water losses have failed to prevent the symptoms. Studies in children have suggested that drinking extra water helps cognitive performance, but these data rely on a small number of children. In older adults (mean age around 60) the data are not strong enough to support a relationship between mild dehydration and cognitive function. Data on frail elderly and demented people are lacking. Methodological heterogeneity in these studies are such that the relationship between mild dehydration and cognitive performance cannot be supported.","title":"Hydration and cognitive performance."},{"docid":"MED-5293","text":"Summary Background Quantification of the disease burden caused by different risks informs prevention by providing an account of health loss different to that provided by a disease-by-disease analysis. No complete revision of global disease burden caused by risk factors has been done since a comparative risk assessment in 2000, and no previous analysis has assessed changes in burden attributable to risk factors over time. Methods We estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010. We estimated exposure distributions for each year, region, sex, and age group, and relative risks per unit of exposure by systematically reviewing and synthesising published and unpublished data. We used these estimates, together with estimates of cause-specific deaths and DALYs from the Global Burden of Disease Study 2010, to calculate the burden attributable to each risk factor exposure compared with the theoretical-minimum-risk exposure. We incorporated uncertainty in disease burden, relative risks, and exposures into our estimates of attributable burden. Findings In 2010, the three leading risk factors for global disease burden were high blood pressure (7·0% [95% uncertainty interval 6·2–7·7] of global DALYs), tobacco smoking including second-hand smoke (6·3% [5·5–7·0]), and alcohol use (5·5% [5·0–5·9]). In 1990, the leading risks were childhood underweight (7·9% [6·8–9·4]), household air pollution from solid fuels (HAP; 7·0% [5·6–8·3]), and tobacco smoking including second-hand smoke (6·1% [5·4–6·8]). Dietary risk factors and physical inactivity collectively accounted for 10·0% (95% UI 9·2–10·8) of global DALYs in 2010, with the most prominent dietary risks being diets low in fruits and those high in sodium. Several risks that primarily affect childhood communicable diseases, including unimproved water and sanitation and childhood micronutrient deficiencies, fell in rank between 1990 and 2010, with unimproved water we and sanitation accounting for 0·9% (0·4–1·6) of global DALYs in 2010. However, in most of sub-Saharan Africa childhood underweight, HAP, and non-exclusive and discontinued breastfeeding were the leading risks in 2010, while HAP was the leading risk in south Asia. The leading risk factor in Eastern Europe, most of Latin America, and southern sub-Saharan Africa in 2010 was alcohol use; in most of Asia, North Africa and Middle East, and central Europe it was high blood pressure. Despite declines, tobacco smoking including second-hand smoke remained the leading risk in high-income north America and western Europe. High body-mass index has increased globally and it is the leading risk in Australasia and southern Latin America, and also ranks high in other high-income regions, North Africa and Middle East, and Oceania. Interpretation Worldwide, the contribution of different risk factors to disease burden has changed substantially, with a shift away from risks for communicable diseases in children towards those for non-communicable diseases in adults. These changes are related to the ageing population, decreased mortality among children younger than 5 years, changes in cause-of-death composition, and changes in risk factor exposures. New evidence has led to changes in the magnitude of key risks including unimproved water and sanitation, vitamin A and zinc deficiencies, and ambient particulate matter pollution. The extent to which the epidemiological shift has occurred and what the leading risks currently are varies greatly across regions. In much of sub-Saharan Africa, the leading risks are still those associated with poverty and those that affect children. Funding Bill & Melinda Gates Foundation.","title":"A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010"},{"docid":"MED-2274","text":"Objective To study the relation between cherry intake and the risk of recurrent gout attacks among individuals with gout. Methods We conducted a case-crossover study to examine associations of a set of putative risk factors with recurrent gout attacks. Individuals with gout were prospectively recruited and followed online for one year. Participants were asked about the following information when experiencing a gout attack: the onset date of the gout attack, symptoms and signs, medications (including anti-gout medications), and potential risk factors (including daily intake of cherries and cherry extract) during the 2-day period prior to the gout attack. We assessed the same exposure information over 2-day control periods. We estimated the risk of recurrent gout attacks related to cherry intake using conditional logistic regression. Results Our study included 633 individuals with gout. Cherry intake over a 2-day period was associated with a 35% lower risk of gout attacks compared with no intake (multivariate odds ratio [OR] = 0.65, 95% CI: 0.50-0.85). Cherry extract intake showed a similar inverse association (multivariate OR=0.55, 95% CI: 0.30-0.98). The effect of cherry intake persisted across subgroups by sex, obesity status, purine intake, alcohol use, diuretic use, and use of anti-gout medications. When cherry intake was combined with allopurinol use, the risk of gout attacks was 75% lower than periods without either exposure (OR=0.25, 95% CI: 0.15-0.42). Conclusions These findings suggest that cherry intake is associated with a lower risk of gout attacks.","title":"Cherry Consumption and the Risk of Recurrent Gout Attacks"},{"docid":"MED-3312","text":"BACKGROUND: Heavy alcohol consumption, viral hepatitis, and diabetes are risk factors for hepatocellular carcinoma (HCC). However, to the authors' knowledge, the information concerning their interaction effect in patients with risk of HCC is sparse. METHODS: A population-based, case-control study of HCC was conducted during 1984-2002. The study involved 295 HCC cases and 435 age-, gender-, and race-matched control subjects among Hispanic and non-Hispanic whites and blacks in Los Angeles County, California. Lifestyle risk factors were ascertained through in-person interviews. Infections with the hepatitis B and C (HCV) viruses were determined using their serologic markers. RESULTS: Fourteen HCC cases but no control subjects tested positive for the hepatitis B surface antigen. Seropositivity for antibodies to HCV was associated with an odds ratio (OR) of 125 (95% confidence interval [95% CI], 17-909) for HCC, whereas seropositivity for antibodies to the hepatitis B core antigen was related to an OR of 2.9 (95% CI, 1.7-5.0). Heavy alcohol consumption and cigarette smoking were found to be independently associated with a statistically significant two to threefold increase in risk of HCC after adjustment for hepatitis B and C serology. Subjects with a history of diabetes had an OR of 2.7 (95% CI, 1.6-4.3) for HCC compared with nondiabetic subjects. A synergistic interaction on HCC risk was observed between heavy alcohol consumption and diabetes (OR = 4.2; 95% CI, 2.6-5.8), heavy alcohol consumption and viral hepatitis (OR = 5.5; 95% CI, 3.9-7.0), or between diabetes and viral hepatitis (OR = 4.8; 95% CI, 2.7-6.9). CONCLUSIONS: Heavy alcohol consumption, diabetes, and viral hepatitis were found to exert independent and synergistic effects on risk of HCC in U.S. blacks and whites. Copyright 2004 American Cancer Society.","title":"Synergism of alcohol, diabetes, and viral hepatitis on the risk of hepatocellular carcinoma in blacks and whites in the U.S."},{"docid":"MED-3123","text":"DietCompLyf is a multi-centre prospective study designed to investigate associations between phytoestrogens - naturally occurring plant compounds with oestrogenic properties - and other diet and lifestyle factors with breast cancer recurrence and survival. 3159 women with grades I-III breast cancer were recruited 9-15 months post-diagnosis from 56 UK hospitals. Detailed information on clinico-pathological, diet, lifestyle and quality of life is collected annually up to 5 years. Biological samples have also been collected as a resource for subsequent evaluation. The characteristics of the patients and associations between pre-diagnosis intake of phytoestrogens (isoflavones and lignans; assessed using the EPIC-Norfolk UK 130 question food frequency questionnaire) and breast cancer (i) risk factors and (ii) prognostic factors are described for 1797 women who had complete data for all covariates and phytoestrogens of interest. Isoflavone intakes were higher in the patients who were younger at diagnosis, in the non-smokers, those who had breast-fed and those who took supplements. Lignan intakes were higher in patients with a higher age at diagnosis, in ex-smokers, those who had breast-fed, who took supplements, had a lower BMI at diagnosis, lower age at menarche and were nulliparous. No significant associations between pre-diagnosis phytoestrogen intake and factors associated with improved breast cancer prognosis were observed. The potential for further exploration of the relationship between phytoestrogens and breast cancer recurrence and survival, and for the establishment of evidence to improve dietary and lifestyle advice offered to patients following breast cancer diagnosis using DietCompLyf data is discussed. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.","title":"The DietCompLyf study: a prospective cohort study of breast cancer survival and phytoestrogen consumption."},{"docid":"MED-2827","text":"Alternative and complementary therapeutic approaches, such as the use of a wide array of herbal, nutritional, and physical manipulations, are becoming popular for relieving symptoms of osteoarthritis (OA). The present study evaluated the efficacy of soy protein (SP) supplementation in relieving the pain and discomfort associated with OA. One hundred and thirty-five free-living individuals (64 men and 71 women) with diagnosed OA or with self-reported chronic knee joint pain not attributed to injury or rheumatoid arthritis were recruited for this double-blind, placebo-controlled, parallel design study. Study participants were assigned randomly to consume 40 g of either supplemental SP or milk-based protein (MP) daily for 3 months. Pain, knee range of motion, and overall physical activity were evaluated prior to the start of treatment and monthly thereafter. Serum levels of glycoprotein 39 (YKL-40), a marker of cartilage degradation, and insulin-like growth factor-I (IGF-I), a growth factor associated with cartilage synthesis, were assessed at baseline and at the end of the study. Overall, SP improved OA-associated symptoms such as range of motion and several factors associated with pain and quality of life in comparison to MP. However, these beneficial effects were mainly due to the effect of SP in men rather than women. Biochemical markers of cartilage metabolism further support the efficacy of SP in men as indicated by a significant increase in serum level of IGF-I and a significant decrease in serum level of YKL-40 compared to MP. This study is the first to provide evidence of possible beneficial effects of SP in the management of OA. Examining and verifying the long-term effects of SP on improving symptoms of OA, particularly in men, is warranted.","title":"Soy protein may alleviate osteoarthritis symptoms."},{"docid":"MED-2458","text":"BACKGROUND: Antioxidant-rich diets are associated with reduced asthma prevalence in epidemiologic studies. We previously showed that short-term manipulation of antioxidant defenses leads to changes in asthma outcomes. OBJECTIVE: The objective was to investigate the effects of a high-antioxidant diet compared with those of a low-antioxidant diet, with or without lycopene supplementation, in asthma. DESIGN: Asthmatic adults (n = 137) were randomly assigned to a high-antioxidant diet (5 servings of vegetables and 2 servings of fruit daily; n = 46) or a low-antioxidant diet (≤2 servings of vegetables and 1 serving of fruit daily; n = 91) for 14 d and then commenced a parallel, randomized, controlled supplementation trial. Subjects who consumed the high-antioxidant diet received placebo. Subjects who consumed the low-antioxidant diet received placebo or tomato extract (45 mg lycopene/d). The intervention continued until week 14 or until an exacerbation occurred. RESULTS: After 14 d, subjects consuming the low-antioxidant diet had a lower percentage predicted forced expiratory volume in 1 s and percentage predicted forced vital capacity than did those consuming the high-antioxidant diet. Subjects in the low-antioxidant diet group had increased plasma C-reactive protein at week 14. At the end of the trial, time to exacerbation was greater in the high-antioxidant than in the low-antioxidant diet group, and the low-antioxidant diet group was 2.26 (95% CI: 1.04, 4.91; P = 0.039) times as likely to exacerbate. Of the subjects in the low-antioxidant diet group, no difference in airway or systemic inflammation or clinical outcomes was observed between the groups that consumed the tomato extract and those who consumed placebo. CONCLUSIONS: Modifying the dietary intake of carotenoids alters clinical asthma outcomes. Improvements were evident only after increased fruit and vegetable intake, which suggests that whole-food interventions are most effective. This trial was registered at http://www.actr.org.au as ACTRN012606000286549.","title":"Manipulating antioxidant intake in asthma: a randomized controlled trial."},{"docid":"MED-4551","text":"Interest has increased in the possibility that maternal dietary intake during pregnancy might influence the development of allergic disorders in children. The present prospective study examined the association of maternal intake of selected foods high in fatty acids and specific types of fatty acids during pregnancy with the risk of suspected atopic eczema among Japanese infants aged 3-4 months. Subjects were 771 mother-child pairs. Information on maternal dietary intake during pregnancy was assessed with a validated self-administered diet history questionnaire. The term 'suspected atopic eczema' was used to define an outcome based on results of our questionnaire completed by mothers 3-4 months postpartum. The risk of suspected atopic eczema was 8.4% (n = 65). Higher maternal intake of meat during pregnancy was significantly associated with an increased risk of suspected atopic eczema in the offspring: the multivariate odds ratio (OR) for the highest vs. lowest quartile was 2.59 [95% confidence interval (CI): 1.15-6.17, p for trend = 0.01]. The positive association was strengthened when the definition of the outcome was confined to a definite physician's diagnosis of atopic eczema (n = 35): the multivariate OR between extreme quartiles was 3.53 (95% CI: 1.19-12.23, p for trend = 0.02). No material exposure-response relationships were observed between maternal intake of eggs, dairy products, fish, total fat, saturated fatty acids, monounsaturated fatty acids, n-3 polyunsaturated fatty acids, alpha-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, n-6 polyunsaturated fatty acids, linoleic acid, arachidonic acid and cholesterol and the ratio of n-3 to n-6 polyunsaturated fatty acid consumption and the risk of suspected atopic eczema. Higher maternal meat intake may increase the risk of infantile atopic eczema, whereas we found no evidence that maternal intake of fish and n-3 polyunsaturated fatty acids are preventive against infantile atopic eczema. (c) 2009 John Wiley & Sons A/S","title":"Maternal meat and fat consumption during pregnancy and suspected atopic eczema in Japanese infants aged 3-4 months: the Osaka Maternal and Child He..."}],"string":"[\n {\n \"docid\": \"MED-3302\",\n \"text\": \"In November 2007 a novel neuropathy, immune-mediated polyradiculoneuropathy (IP), was identified among workers at a Minnesota swine abattoir where a unique compressed air technique was used to remove porcine brains. An epidemiologic investigation at another abattoir in Indiana that also uses this process was launched to evaluate workers self-reporting neurologic illness compatible with IP. A nested case-control study was performed to identify cases and risk factors. Six confirmed, one probable, and three possible IP cases were detected. IP cases were 28-52 years old, of Latino origin, and 62.5% female. Onset dates ranged from April 2005-December 2007; 60% were hospitalized. IP cases at this plant were similar in clinical presentation and exposure risks to those detected in Minnesota. Swine abattoirs using similar brain extraction methods should discontinue this process.\",\n \"title\": \"A clustering of immune-mediated polyradiculoneuropathy among swine abattoir workers exposed to aerosolized porcine brains, Indiana, United States.\"\n },\n {\n \"docid\": \"MED-2644\",\n \"text\": \"Alkylphenols are widely used as plastic additives and surfactants. We report the identification of an alkylphenol, nonylphenol, as an estrogenic substance released from plastic centrifuge tubes. This compound was extracted with methanol, purified by flash chromatography and reverse-phase high performance liquid chromatography, and identified by gas chromatography-mass spectrometry. Nonylphenol induced both cell proliferation and progesterone receptor in human estrogen-sensitive MCF7 breast tumor cells. Nonylphenol also triggered mitotic activity in rat endometrium; this result confirms the reliability of the MCF7 cell proliferation bioassay. The estrogenic properties of alkylphenols, specifically nonylphenols, indicate that the use of plasticware containing these chemicals in experimental and diagnostic tests may lead to spurious results, and these compounds as well as alkylphenol polyethoxylates may also be potentially harmful to exposed humans and the environment at large.\",\n \"title\": \"p-Nonyl-phenol: an estrogenic xenobiotic released from \\\"modified\\\" polystyrene.\"\n },\n {\n \"docid\": \"MED-2210\",\n \"text\": \"We investigated the effects of sporamin, the major soluble protein with a kunitz-type trypsin inhibitory activity in the root tuber of the sweet potato, on cell proliferation, apoptosis, Akt/GSK-3 signaling and its related genes to provide more insights in the mechanism behind the inhibitory effects of sporamin in a human tongue cancer line Tca8113. In this study, sporamin inhibited cell proliferation and induced apoptosis in Tca8113 cells in a concentration-dependent and time-dependent manner. Consistently, Bax was up-regulated and Bcl-2 was down-regulated in sporamin-treated cells. Furthermore, Akt/GSK-3 signaling was down-regulated in sporamin-treated cells. Consistently, the phosphorylated Bad was significantly declined in sporamin-treated Tca8113 cells. These results suggest the antiproliferative effects of sporamin in Tca8113 cells might result partly from induction of apoptosis by down-regulating Akt/GSK-3 pathway. © 2010 The Authors Fundamental and Clinical Pharmacology © 2010 Société Française de Pharmacologie et de Thérapeutique.\",\n \"title\": \"Sporamin induce apoptosis in human tongue carcinoma cells by down-regulating Akt/GSK-3 signaling.\"\n },\n {\n \"docid\": \"MED-2652\",\n \"text\": \"The exposure to some chemicals can lead to hormone disrupting effects. Presently, much attention is focused on so-called xeno-estrogens, synthetic compounds that interact with hormone receptors causing a number of reactions that eventually lead to effects related to reproduction and development. The current study was initiated to investigate the presence of a number of such compounds in precipitation as a follow-up on a previous study in which pesticide concentrations in air and precipitation were determined. Rainwater samples were collected at about 50 locations in The Netherlands in a four week period. The samples were analysed for bisphenol-A, alkylphenols and alkylphenol ethoxylates, phthalates, flame retardants and synthetic musk compounds. The results clearly indicated the presence of these compounds in precipitation. The concentrations ranged from the low ng l(-1) range for flame retardants to several thousands of ng l(-1) for the phthalates. Bisphenol-A was found in 30% of the samples in concentrations up to 130 ng l(-1), while alkylphenols and alkylphenol ethoxylates were found in virtually all locations in concentrations up to 920 ng l(-1) for the individual compounds. Phthalates were by far the most abundant xeno-estrogens in the precipitation samples and were found in every sample. Di-isodecyl phthalate was found in a surprisingly high concentration of almost 100 000 ng l(-1). Polybrominated flame retardants were found in the low ng l(-1) range and generally in less than 20% of the samples. Noticeable was the finding of hexabromocyclododecane, a replacement for the polybrominted diphenyl ethers at one location in a concentration of almost 2000 ng l(-1). Finally, as expected, synthetic musk compounds were detected in almost all samples. This is especially true for the polycyclic musks HHCB and AHTN. Nitro musks were found, but only on a few locations. Kriging techniques were used to calculate precipitation concentrations in between actual sampling locations to produce contour plots for a number of compounds. These plots clearly show located emission sources for a number of compounds such as bisphenol-A, nonylphenol ethoxylate, phthalates and AHTN. On the contrary, the results for HHCB and some phthalates indicated diffuse emission patterns, probably as the result of the use of consumer products containing these compounds.\",\n \"title\": \"Xeno-estrogenic compounds in precipitation.\"\n },\n {\n \"docid\": \"MED-4954\",\n \"text\": \"BACKGROUND To look at possible long-term risks from anabolic steroids and other xenobiotics in beef, we examined men's semen quality in relation to their mother's self-reported beef consumption during pregnancy. METHODS: The study was carried out in five US cities between 1999 and 2005. We used regression analyses to examine semen parameters in 387 partners of pregnant women in relation to the amount of beef their mothers reported eating while pregnant. Mothers' beef consumption was also analysed in relation to the son's history of previous subfertility. RESULTS Sperm concentration was inversely related to mothers' beef meals per week (P = 0.041). In sons of \\\"high beef consumers\\\" (>7 beef meals/week), sperm concentration was 24.3% lower (P = 0.014) and the proportion of men with sperm concentration below 20 x 10(6)/ml was three times higher (17.7 versus 5.7%, P = 0.002) than in men whose mothers ate less beef. A history of previous subfertility was also more frequent among sons of \\\"high beef consumers\\\" (P = 0.015). Sperm concentration was not significantly related to mother's consumption of other meat or to the man's consumption of any meat. CONCLUSIONS These data suggest that maternal beef consumption, and possibly xenobiotics in beef, may alter a man's testicular development in utero and adversely affect his reproductive capacity.\",\n \"title\": \"Semen quality of fertile US males in relation to their mothers' beef consumption during pregnancy.\"\n },\n {\n \"docid\": \"MED-1253\",\n \"text\": \"OBJECTIVES: To investigate the effect of replacing lean meat with a soy product, tofu, on serum lipoprotein concentrations. STUDY AND DESIGN: Randomized cross-over dietary intervention study. SUBJECTS: Forty-two free-living healthy males aged 35-62 y completed the dietary intervention. Three additional subjects were non-compliant and excluded prior to analysis. INTERVENTIONS: A diet containing lean meat (150 g/d) was compared with one with 290 g/d tofu in an isocaloric and isoprotein substitution. Both diet periods were 1 month, and fat intake was carefully controlled. RESULTS: Seven-day diet records showed the two diets were similar in energy, macronutrients and fibre. Total cholesterol (mean difference 0.23 mmol/l, 95% CI 0.02, 0.43; P=0.03) and triglycerides (mean difference 0.15 mmol/l, 95% CI 0.02, 0.31; P=0.017) were significantly lower on the tofu diet than the lean meat diet. However, HDL-C was also significantly lower on the tofu diet (mean difference 0.08 mmol/l, 95% CI 0.02, 0.14; P=0.01) although the LDL-C:HDL-C ratio was similar. CONCLUSION: The effect on HDL-C and the small LDL-C reduction differ from some other studies, where fat was often less controlled, and the comparison was of soy as textured protein or soymilk against casein. This suggests a differential effect of the various proteins compared to the soy may influence the findings. In practice, the replacement of meat with tofu would usually be associated with a decrease in saturated fat and an increase in polyunsaturated fat and this should enhance any small benefits due to the soy protein. SPONSOR: Deakin University with some contribution from a Commonwealth Department of Veterans Affairs research grant. European Journal of Clinical Nutrition (2000) 54, 14-19\",\n \"title\": \"Effects of soy as tofu vs meat on lipoprotein concentrations.\"\n },\n {\n \"docid\": \"MED-3784\",\n \"text\": \"Dietary choline and betaine have been hypothesized to decrease the risk of cancer because of their role as methyl donors in the one-carbon metabolism. However, it remains unknown whether dietary intake of choline and betaine is associated with colorectal cancer risk. We prospectively examined the associations between dietary choline and betaine intake and risk of colorectal cancer in men in the Health Professionals Follow-up Study. We followed 47,302 men and identified a total of 987 incident colorectal cancer cases from 1986 to 2004. We assessed dietary and supplemental choline and betaine intake every four years using a validated semi-quantitative food frequency questionnaire. The Cox proportional hazards model was used to estimate multivariate relative risks (RRs) and 95% confidence intervals (95% CIs). All statistical tests were two-sided. We did not find any statistically significant associations between choline intake or betaine intake and risk of colorectal cancer. Comparing the top quintile with bottom quintile, multivariate RRs (95% CI) were 0.97 (0.79-1.20; Ptrend = 0.87) for choline intake and 0.94 (0.77-1.16; Ptrend = 0.79) for betaine intake. Similarly, we observed no associations between colorectal cancer risk and choline from free choline, glycerophosphocholine, phosphocholine, phosphatidylcholine, or sphingomyelin. Our data do not support that choline and betaine intake is inversely associated with colorectal cancer risk.\",\n \"title\": \"Choline and betaine intake and the risk of colorectal cancer in men\"\n },\n {\n \"docid\": \"MED-1252\",\n \"text\": \"The effect of substituting soy for animal protein in mixed diets was determined in young men with mildly elevated plasma cholesterol, 218 to 307 mg/dl. The diets were low in cholesterol, 200 mg/day, with 13 to 16% of energy as protein, 30 to 35% as fat, and a polyunsaturated to saturated fat ratio of 0.5. Of protein 65% was from either mixed animal proteins or isolated soy protein products made comparable by the addition of extracted animal fats. Fresh egg yolk was added to balance the cholesterol content of the diets. Proteins from grains and vegetables were identical in both menus and contributed about 35% of dietary protein. Twenty of 24 subjects decreased plasma cholesterol at the end of the protocol. Subjects were classified as responders or nonresponders as a function of greater or lesser than mean reduction in cholesterol for the groups. Mean decreases in plasma cholesterol, 16 and 13%, for responders in the animal and soy groups were significant, p less than 0.01 and 0.05, respectively. Responders in both groups had higher initial plasma cholesterol values than nonresponders. Although plasma high-density lipoprotein cholesterol decreased slightly, the high-density lipoprotein cholesterol to cholesterol ratio (high-density lipoprotein cholesterol/total cholesterol) remained constant for most individuals. The hypocholesterolemic effects were similar for both animal and soy protein (p less than 0.05) and fat (p less than 0.05) while on the experimental diet. All groups significantly decreased dietary cholesterol (p less than 0.001).\",\n \"title\": \"Determinants of hypocholesterolemic response to soy and animal protein-based diets.\"\n },\n {\n \"docid\": \"MED-3220\",\n \"text\": \"Background Maintaining muscle mass while aging is important to prevent falls and fractures. Metabolic acidosis promotes muscle wasting, and the net acid load from diets that are rich in net acid–producing protein and cereal grains relative to their content of net alkali–producing fruit and vegetables may therefore contribute to a reduction in lean tissue mass in older adults. Objective We aimed to determine whether there was an association of 24-h urinary potassium and an index of fruit and vegetable content of the diet with the percentage lean body mass (%LBM) or change in %LBM in older subjects. Design Subjects were 384 men and women ≥65 y old who participated in a 3-y trial comparing calcium and vitamin D with placebo. Potassium was measured in 24-h urine collections at baseline. The %LBM, defined as total body nonfat, nonbone tissue weight ÷ weight × 100, was measured by using dual-energy X-ray absorptiometry at baseline and at 3 y. Physical activity, height, and weight were assessed at baseline and at 3 y. Results At baseline, the mean urinary potassium excretion was 67.0 ± 21.1 mmol/d. Urinary potassium (mmol/d) was significantly positively associated with %LBM at baseline (β = 0.033, P = 0.006; adjusted for sex, weight, and nitrogen excretion) but not with 3-y change in %LBM. Over the 3-y study, %LBM increased by 2.6 ± 3.6%. Conclusion Higher intake of foods rich in potassium, such as fruit and vegetables, may favor the preservation of muscle mass in older men and women.\",\n \"title\": \"Alkaline diets favor lean tissue mass in older adults\"\n },\n {\n \"docid\": \"MED-3878\",\n \"text\": \"Diet, nutritional status, and certain dietary supplements are postulated to influence the development and progression of prostate cancer. Angiogenesis and inflammation are central to tumor growth and progression, but the effect of diet on these processes remains uncertain. We explored changes in 50 plasma cytokines and angiogenic factors (CAFs) in 145 men with prostate cancer enrolled in a pre-operative, randomized controlled phase-II trial with four arms: control (usual diet); low-fat (LF) diet; flaxseed-supplemented (FS) diet; and flaxseed-supplemented, low-fat diet. The mean duration of dietary intervention was 30–31 days. Among the individual arms, the largest number of significant changes (baseline vs pre-operative follow-up) was observed in the LF arm, with 19 CAFs decreasing and one increasing (p<.05). Compared to the control arm, 6 CAFs—including pro-angiogenic factors (stromal-cell derived-1α and myeloid factors (granulocyte-colony-stimulating factor, macrophage colony-stimulating factor — all decreased in the LF arm compared to controls; 3 and 4 CAFs changed in the FS and FS+LF arms, respectively. Weight loss occurred in the LF arms and significantly correlated with VEGF decreases (P <0.001). The CAFs that changed in the LF arm are all known to be regulated by nuclear factor-kappa B (NF-κB), and a pathway analysis identified NF-κB as the most likely regulatory network associated with these changes in the LF arm, but not in the FS-containing arms. These results suggest that a low-fat diet without flaxseed may reduce levels of specific inflammatory cytokines and angiogenic factors and suggests that the NF-κB pathway may be a mediator of these changes.\",\n \"title\": \"Effect of Low-fat Diets on Plasma Levels of NFκB-regulated Inflammatory Cytokines and Angiogenic Factors in Men with Prostate Cancer\"\n },\n {\n \"docid\": \"MED-2452\",\n \"text\": \"A role for diet in the pathophysiology of asthma may be mediated by altered immune or antioxidant activity with consequent effects on airway inflammation. We evaluated associations between several dietary factors assessed by a semiquantitative food frequency questionnaire, and incidence of asthma over a 10-yr period in 77,866 women 34 to 68 yr of age. Women in the highest quintile of vitamin E intake from diet, but not from supplements, had a risk of 0.53 (95% confidence interval [CI] = 0.33 to 0.86) compared with women in the lowest quintile. This relationship, however, was attenuated when the contribution from nuts, a major source of vitamin E in these data and a possible allergen, was removed (relative risk = 0.74 [0.50 to 1.10], p for trend = 0.007). Positive associations were found for vitamins C and E from supplements, but appeared to be explained by women at high risk of asthma initiating use of vitamin supplements prior to diagnosis. A nonsignificant inverse association with carotene intake was noted, but no clear relations with asthma were demonstrated for intake of linoleic acid or omega-3 fatty acids. These data suggest that antioxidant supplementation and intake of various fats during adulthood are not important determinants of asthma, although vitamin E from diet may have a modest protective effect.\",\n \"title\": \"A prospective study of diet and adult-onset asthma.\"\n },\n {\n \"docid\": \"MED-2126\",\n \"text\": \"Increased protein supply by feeding cow-milk-based infant formula in comparison to lower protein content of human milk is a well-recognized major risk factor of childhood obesity. However, there is yet no conclusive biochemical concept explaining the mechanisms of formula-induced childhood obesity. It is the intention of this article to provide the biochemical link between leucine-mediated signalling of mammalian milk proteins and adipogenesis as well as early adipogenic programming. Leucine has been identified as the predominant signal transducer of mammalian milk, which stimulates the nutrient-sensitive kinase mammalian target of rapamycin complex 1 (mTORC1). Leucine thus functions as a maternal-neonatal relay for mTORC1-dependent neonatal β-cell proliferation and insulin secretion. The mTORC1 target S6K1 plays a pivotal role in stimulation of mesenchymal stem cells to differentiate into adipocytes and to induce insulin resistance. It is of most critical concern that infant formulas provide higher amounts of leucine in comparison to human milk. Exaggerated leucine-mediated mTORC1-S6K1 signalling induced by infant formulas may thus explain increased adipogenesis and generation of lifelong elevated adipocyte numbers. Attenuation of mTORC1 signalling of infant formula by leucine restriction to physiologic lower levels of human milk offers a great chance for the prevention of childhood obesity and obesity-related metabolic diseases.\",\n \"title\": \"Excessive Leucine-mTORC1-Signalling of Cow Milk-Based Infant Formula: The Missing Link to Understand Early Childhood Obesity\"\n },\n {\n \"docid\": \"MED-4060\",\n \"text\": \"Heteroyclic aromatic amines (HAAs) are a class of hazardous chemicals that are receiving heightened attention as a risk factor for human cancer. HAAs arise during the cooking of meats, fish, and poultry, and several HAAs also occur in tobacco smoke condensate and diesel exhaust. Many HAAs are carcinogenic and induce tumors at multiple sites in rodents. A number of epidemiologic studies have reported that frequent consumption of well-done cooked meats containing HAAs can result in elevated risks for colon, prostate, and mammary cancers. Moreover, DNA adducts of HAAs have been detected in human tissues, demonstrating that HAAs induce genetic damage even though the concentrations of these compounds in cooked meats are generally in the low parts-per-billion (ppb) range. With recent improvements in sensitivity of mass spectrometry instrumentation, HAAs, their metabolites, and DNA adducts can be detected at trace amounts in biological fluids and tissues of humans. The incorporation of HAA biomarkers in epidemologic studies will help to clarify the role of these dietary genotoxicants in the etiology of human cancer.\",\n \"title\": \"Formation and biochemistry of carcinogenic heterocyclic aromatic amines in cooked meats.\"\n },\n {\n \"docid\": \"MED-2332\",\n \"text\": \"Plants have evolved a variety of responses to elevated temperatures that minimize damage and ensure protection of cellular homeostasis. New information about the structure and function of heat stress proteins and molecular chaperones has become available. At the same time, transcriptome analysis of Arabidopsis has revealed the involvement of factors other than classical heat stress responsive genes in thermotolerance. Recent reports suggest that both plant hormones and reactive oxygen species also contribute to heat stress signaling. Additionally, an increasing number of mutants that have altered thermotolerance have extended our understanding of the complexity of the heat stress response in plants.\",\n \"title\": \"Complexity of the heat stress response in plants.\"\n },\n {\n \"docid\": \"MED-2333\",\n \"text\": \"Until recently, the study and understanding of plant and animal signalling and response mechanisms have developed independently. Recent biochemical and molecular work is producing a growing list of elements involved in responses to biotic and abiotic stimuli that are very similar across kingdoms. Some of the more interesting examples of these include prostaglandin/octadecanoid-mediated responses to wounding, steroid-based signalling systems, and pathogen-recognition mechanisms. Some of these similarities probably represent evolutionary convergence; others may be ancestral to plants and animals. Ecological and evolutionary implications of such overlaps include the existence of pathogens that can cause disease in plants and animals, the ability of herbivores to manipulate plant responses, usurpation of microbial mechanisms and genes by herbivorous animals and plants, evolution of plant defenses exploiting shared signals in animals, and the medicinal use of plants by humans. Comparative study of the signalling and response mechanisms used by plants, animals, and microbes provides novel and useful insights to the ecology and evolution of interactions across kingdoms.\",\n \"title\": \"Shared signals and the potential for phylogenetic espionage between plants and animals.\"\n },\n {\n \"docid\": \"MED-3450\",\n \"text\": \"Although assays for the most popular markers of exercise-induced oxidative stress may experience methodological flaws, there is sufficient credible evidence to suggest that exercise is accompanied by an increased generation of free radicals, resulting in a measurable degree of oxidative modifications to various molecules. However, the mechanisms responsible are unclear. A common assumption that increased mitochondrial oxygen consumption leads per se to increased reactive oxygen species (ROS) production is not supported by in vitro and in vivo data. The specific contributions of other systems (xanthine oxidase, inflammation, haem protein auto-oxidation) are poorly characterised. It has been demonstrated that ROS have the capacity to contribute to the development of muscle fatigue in situ, but there is still a lack of convincing direct evidence that ROS impair exercise performance in vivo in humans. It remains unclear whether exercise-induced oxidative modifications have little significance, induce harmful oxidative damage, or are an integral part of redox regulation. It is clear that ROS play important roles in numerous physiological processes at rest; however, the detailed physiological functions of ROS in exercise remain to be elucidated.\",\n \"title\": \"Exercise-induced oxidative stress:myths, realities and physiological relevance.\"\n },\n {\n \"docid\": \"MED-4040\",\n \"text\": \"The consumption of cooked meat appears to predispose individuals to colonic cancer and heterocyclic aromatic amines (HA), formed during the cooking of meat, have been suggested as aetiological agents. Consumption of cruciferous vegetables is thought to protect against cancer. To study the effect of cruciferous vegetables on heterocyclic aromatic amine metabolism in man, a three-period, dietary intervention study has been carried out with 20 non-smoking Caucasian male subjects consuming cooked meat meals containing known amounts of these carcinogens. A high cruciferous vegetable diet (250 g each of Brussels sprouts and broccoli per day) was maintained during period 2 but such vegetables were excluded from periods 1 and 3. At the end of each period, subjects consumed a cooked meat meal and urinary excretion of the HA 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) was measured. Following a 12 day period of cruciferous vegetable consumption (period 2), induction of hepatic CYP1A2 activity was apparent from changes in the kinetics of caffeine metabolism. Excretion of MeIQx and PhIP in urine at the end of this period of the study was reduced by 23 and 21%, respectively, compared with period 1. This reduction in excretion is probably due to an increase in amine metabolism that might be expected given the observed increase in CYP1A2 activity, since this enzyme has been shown to be primarily responsible for the oxidative activation of MeIQx and PhIP in man. In period 2, urinary mutagenicity was increased relative to period 1 by 52 and 64% in the absence and presence, respectively, of a human liver microsomal activation system, yet no evidence was found of PhIP adduction to lymphocyte DNA, a potential biomarker of the activation process. After another 12 days without cruciferous vegetables (period 3 of the study), the kinetics of caffeine metabolism had returned to original values but excretion of MeIQx and PhIP was still reduced by 17 and 30%, respectively, and urinary mutagenicity (with metabolic activation) was still elevated compared with period 1. This prolonged response of amine metabolism to the cruciferous vegetable diet, shown especially with PhIP, suggests that enzyme systems other than CYP1A2 are involved and affected by a cruciferous vegetable diet.\",\n \"title\": \"Effect of cruciferous vegetable consumption on heterocyclic aromatic amine metabolism in man.\"\n },\n {\n \"docid\": \"MED-2479\",\n \"text\": \"BACKGROUND: The prevalence of allergic diseases seems to have increased particularly over the past 35-40 years. Furthermore, allergic disease is less common among children in the formerly socialist countries of central and Eastern Europe as compared with Western Europe. It has been suggested that a reduced microbial stimulation during infancy and early childhood would result in a slower postnatal maturation of the immune system and development of an optimal balance between TH1- and TH2-like immunity. AIMS: To test the hypothesis that allergic disease among children may be associated with differences in their intestinal microflora in two countries with a low (Estonia) and a high (Sweden) prevalence of allergy. METHODS: From a prospective study of the development of allergy in relation to environmental factors, 29 Estonian and 33 Swedish 2-year-old children were selected. They were either nonallergic (n = 36) or had a confirmed diagnosis of allergy (n = 27) as verified by typical history and at least one positive skin prick test to egg or cow's milk. Weighed samples of faeces were serially diluted (10-2-10-9) and grown under anaerobic conditions. The counts of the various genera and species were calculated for each child. In addition, the relative amounts of the particular microbes were expressed as a proportion of the total count. RESULTS: The allergic children in Estonia and Sweden were less often colonized with lactobacilli (P < 0.01), as compared with the nonallergic children in the two countries. In contrast, the allergic children harboured higher counts of aerobic micro-organisms (P < 0. 05), particularly coliforms (P < 0.01) and Staphylococcus aureus (P < 0.05). The proportions of aerobic bacteria of the intestinal flora were also higher in the allergic children (P < 0.05), while the opposite was true for anaerobes (P < 0.05). Similarly, in the allergic children the proportions of coliforms were higher (P < 0. 05) and bacteroides lower (P < 0.05) than in the nonallergic children. CONCLUSIONS: Differences in the indigenous intestinal flora might affect the development and priming of the immune system in early childhood, similar to what has been shown in rodents. The role of intestinal microflora in relation to the development of infant immunity and the possible consequences for allergic diseases later in life requires further study, particularly as it would be readily available for intervention as a means for primary prevention of allergy by the administration of probiotic bacteria.\",\n \"title\": \"The intestinal microflora in allergic Estonian and Swedish 2-year-old children.\"\n },\n {\n \"docid\": \"MED-1718\",\n \"text\": \"The number of cancer cases caused by being obese is estimated to be 20% with the increased risk of malignancies being influenced by diet, weight change, and body fat distribution together with physical activity. Reports from the International Agency for Research into Cancer and the World Cancer Research Fund (WCRF) have shown that the strongest evidence exists for an association of obesity with the following cancer types: endometrial, esophageal adenocarcinoma, colorectal, postmenopausal breast, prostate, and renal, whereas the less common malignancies are leukemia, non-Hodgkin's lymphoma, multiple myeloma, malignant melanoma, and thyroid tumours. To be able to develop novel methods in prevention and treatment, we first must understand the underlying processes which link cancer to obesity. Four main systems have been identified as potential producers of cancer in obesity: insulin, insulin-like growth factor-I, sex steroids, and adipokines. Various novel candidate mechanisms have been proposed: chronic inflammation, oxidative stress, crosstalk between tumour cells and surrounding adipocytes, migrating adipose stromal cells, obesity-induced hypoxia, shared genetic susceptibility, and the functional defeat of immune function. Herein, we review the major pathogenic links between obesity and susceptibility to cancer.\",\n \"title\": \"Obesity as a Major Risk Factor for Cancer\"\n },\n {\n \"docid\": \"MED-1717\",\n \"text\": \"BACKGROUND: Excess bodyweight, expressed as increased body-mass index (BMI), is associated with the risk of some common adult cancers. We did a systematic review and meta-analysis to assess the strength of associations between BMI and different sites of cancer and to investigate differences in these associations between sex and ethnic groups. METHODS: We did electronic searches on Medline and Embase (1966 to November 2007), and searched reports to identify prospective studies of incident cases of 20 cancer types. We did random-effects meta-analyses and meta-regressions of study-specific incremental estimates to determine the risk of cancer associated with a 5 kg/m2 increase in BMI. FINDINGS: We analysed 221 datasets (141 articles), including 282,137 incident cases. In men, a 5 kg/m2 increase in BMI was strongly associated with oesophageal adenocarcinoma (RR 1.52, p<0.0001) and with thyroid (1.33, p=0.02), colon (1.24, p<0.0001), and renal (1.24, p <0.0001) cancers. In women, we recorded strong associations between a 5 kg/m2 increase in BMI and endometrial (1.59, p<0.0001), gallbladder (1.59, p=0.04), oesophageal adenocarcinoma (1.51, p<0.0001), and renal (1.34, p<0.0001) cancers. We noted weaker positive associations (RR <1.20) between increased BMI and rectal cancer and malignant melanoma in men; postmenopausal breast, pancreatic, thyroid, and colon cancers in women; and leukaemia, multiple myeloma, and non-Hodgkin lymphoma in both sexes. Associations were stronger in men than in women for colon (p<0.0001) cancer. Associations were generally similar in studies from North America, Europe and Australia, and the Asia-Pacific region, but we recorded stronger associations in Asia-Pacific populations between increased BMI and premenopausal (p=0.009) and postmenopausal (p=0.06) breast cancers. INTERPRETATION: Increased BMI is associated with increased risk of common and less common malignancies. For some cancer types, associations differ between sexes and populations of different ethnic origins. These epidemiological observations should inform the exploration of biological mechanisms that link obesity with cancer.\",\n \"title\": \"Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies.\"\n },\n {\n \"docid\": \"MED-3228\",\n \"text\": \"A precise understanding of the role of dietary protein in bone health has been evasive despite decades of research. It is known that a dietary acid load is harmful to bone, and sulfur-containing amino acids are metabolized to provide such an acid load. It is also known that protein elevates urine calcium loss. However, recent clinical studies and a meta-analysis have indicated either no effect or a modest benefit associated with higher protein intakes. These contradictory considerations may be explained by the existence of a two-faced relationship between protein and bone, with simultaneous positive and negative pathways. In opposition to the negative effects of dietary acid load, protein may exert positive effects related to improving calcium absorption, increasing insulin-like growth factor 1, or improving lean body mass, which, in turn, improves bone strength. Putative mechanisms behind these pathways are reviewed here, and some limitations in the historical literature as well as suggested measures to counter these in the future are identified. When positive and negative pathways are considered in tandem, protein may offer modest benefits to bone in the presence of adequate dietary calcium and acid-neutralizing fruits and vegetables. © 2011 International Life Sciences Institute.\",\n \"title\": \"Dietary protein and bone health: harmonizing conflicting theories.\"\n },\n {\n \"docid\": \"MED-3318\",\n \"text\": \"Smoking is an established risk factor for pancreatic cancer; however, detailed examination of the association of smoking intensity, smoking duration, and cumulative smoking dose with pancreatic cancer is limited. The authors analyzed pooled data from the international Pancreatic Cancer Cohort Consortium nested case-control study (1,481 cases, 1,539 controls). Odds ratios and 95% confidence intervals were calculated by using unconditional logistic regression. Smoking intensity effects were examined with an excess odds ratio model that was linear in pack-years and exponential in cigarettes smoked per day and its square. When compared with never smokers, current smokers had a significantly elevated risk (odds ratio (OR) = 1.77, 95% confidence interval (CI): 1.38, 2.26). Risk increased significantly with greater intensity (≥30 cigarettes/day: OR = 1.75, 95% CI: 1.27, 2.42), duration (≥50 years: OR = 2.13, 95% CI: 1.25, 3.62), and cumulative smoking dose (≥40 pack-years: OR = 1.78, 95% CI: 1.35, 2.34). Risk more than 15 years after smoking cessation was similar to that for never smokers. Estimates of excess odds ratio per pack-year declined with increasing intensity, suggesting greater risk for total exposure delivered at lower intensity for longer duration than for higher intensity for shorter duration. This finding and the decline in risk after smoking cessation suggest that smoking has a late-stage effect on pancreatic carcinogenesis.\",\n \"title\": \"Cigarette Smoking and Pancreatic Cancer: A Pooled Analysis From the Pancreatic Cancer Cohort Consortium\"\n },\n {\n \"docid\": \"MED-2207\",\n \"text\": \"The objective of this study was to investigate the antiproliferative effect and the mechanism of trypsin inhibitor (TI) from sweet potato [Ipomoea batatas (L.) Lam. 'Tainong 57'] storage roots on NB4 promyelocytic leukemia cells. The results showed that TI inhibited cellular growth of NB4 promyelocytic leukemia cells in a time-dependent and dose-dependent manner, and treatment for 72 h induced a marked inhibition of cellular growth, showing an IC50 of 57.1 +/- 8.26 microg/mL. TI caused cell cycle arrest at the G1 phase as determined by flow cytometric analysis and apoptosis as shown by DNA laddering. TI-induced cell apoptosis involved p53, Bcl-2, Bax, and cytochrome c protein in NB4 cells. P53 and Bax proteins were accumulated, and antiapoptotic molecule Bcl-2 was decreased in the tested cells in a time-dependent manner during TI treatment. TI also induced a substantial release of cytochrome c from the mitochondria into the cytosol. Hence, TI induced apoptosis in NB4 cells through a mitochondria-dependent pathway, which was associated with the activation of caspase-3 and -8. These results demonstrated that TI induces NB4 cell apoptosis through the inhibition of cell growth and the activation of the pathway of caspase-3 and -8 cascades.\",\n \"title\": \"Growth inhibition and induction of apoptosis in NB4 promyelocytic leukemia cells by trypsin inhibitor from sweet potato storage roots.\"\n },\n {\n \"docid\": \"MED-1186\",\n \"text\": \"We investigated the effect of resistant starch (RS) on markers of colonic protein metabolism. Eleven subjects participated in a randomized crossover study in which they consumed either high-RS (39 +/- 3 g/d, -chi +/- SEM) or low-RS (5 +/- 0.4 g/d) diets for 3 wk. All other macronutrients were kept constant. During the high-RS diet daily excretion of fecal nitrogen increased from 1.84 +/- 0.15 to 2.86 +/- 0.42 g/d (P < 0.01) and excretion of fecal phenols fell from 9.2 +/- 1.4 to 5.3 +/- 0.8 mg/d (P < 0.01). Fecal concentrations of ammonia decreased from 397 +/- 33 to 278 +/- 49 microgram/g (P < 0.01) and phenols decreased from 69 +/- 8 to 39 +/- 10 microgram/g (P < 0.001). Daily output of urinary ammonia, urea, phenols, and total nitrogen did not change significantly, but pH decreased from 6.4 +/- 0.1 to 6.2 +/- 0.1 (P < 0.05) during the high-RS period. These results suggest that RS significantly attenuates the accumulation of potentially harmful byproducts of protein fermentation in the human colon.\",\n \"title\": \"Resistant starch lowers fecal concentrations of ammonia and phenols in humans.\"\n },\n {\n \"docid\": \"MED-3279\",\n \"text\": \"Various pesticides are being used to destabilize, perturb, or inhibit crucial biochemical and physiological targets related to metabolism, growth, development, nervous communication, or behavior in pestiferous organisms. Chitin is an eukaryotic extracellular aminosugar biopolymer, massively produced by most fungal systems and by invertebrates, notably arthropods. Being an integral supportive component in fungal cell wall, insect cuticle, and nematode egg shell, chitin has been considered as a selective target for pesticide action. Throughout the elaborate processes of chitin formation and deposition, only the polymerization events associated with the cell membrane compartment are so far available for chemical interference. Currently, the actinomycetes-derived nucleoside peptide fungicides such as the polyoxins and the insecticidal benzoylaryl ureas have reached commercial pesticide status. The polyoxins and other structurally-related antibiotics like nikkomycins are strong competitive inhibitors of the polymerizing enzyme chitin synthase. The exact biochemical lesion inflicted by the benzoylaryl ureas is still elusive, but a post-polymerization event, such as translocation of chitin chains across the cell membrane, is suggested. Hydrolytic degradation of the chitin polymer is essential for hyphal growth, branching, and septum formation in fungal systems as well as for the normal molting of arthropods. Recently, insect chitinase activity was strongly and specifically suppressed by allosamidin, an actimomycetes-derived metabolite. In part, the defense mechanism in plants against invasion of pathogens is associated with induced chitinases. Chitin, chitosan, and their oligomers are able to act as elicitors which induce enhanced levels of chitinases in various plants. Lectins which bind to N-acetyl-D-glucosamine strongly interfere with fungal and insect chitin synthases. Plant lectins with similar properties may be involved in plant-pathogen interaction inter alia by suppressing fungal invasion.\",\n \"title\": \"Chitin synthesis and degradation as targets for pesticide action.\"\n },\n {\n \"docid\": \"MED-4233\",\n \"text\": \"OBJECTIVES: Dietary fat and fiber affect hormonal levels and may influence cancer progression. Flaxseed is a rich source of lignan and omega-3 fatty acids and may thwart prostate cancer. The potential effects of flaxseed may be enhanced with concomitant fat restriction. We undertook a pilot study to explore whether a flaxseed-supplemented, fat-restricted diet could affect the biomarkers of prostatic neoplasia. METHODS: Twenty-five patients with prostate cancer who were awaiting prostatectomy were instructed on a low-fat (20% of kilocalories or less), flaxseed-supplemented (30 g/day) diet. The baseline and follow-up levels of prostate-specific antigen, testosterone, free androgen index, and total serum cholesterol were determined. The tumors of diet-treated patients were compared with those of historic cases (matched by age, race, prostate-specific antigen level at diagnosis, and biopsy Gleason sum) with respect to apoptosis (terminal deoxynucleotidyl transferase [TdT]-mediated dUTP-biotin nick end-labeling [TUNEL]) and proliferation (MIB-1). RESULTS: The average duration on the diet was 34 days (range 21 to 77), during which time significant decreases were observed in total serum cholesterol (201 +/- 39 mg/dL to 174 +/- 42 mg/dL), total testosterone (422 +/- 122 ng/dL to 360 +/- 128 ng/dL), and free androgen index (36.3% +/- 18.9% to 29.3% +/- 16.8%) (all P <0.05). The baseline and follow-up levels of prostate-specific antigen were 8.1 +/- 5.2 ng/mL and 8.5 +/- 7.7 ng/mL, respectively, for the entire sample (P = 0.58); however, among men with Gleason sums of 6 or less (n = 19), the PSA values were 7.1 +/- 3.9 ng/mL and 6.4 +/- 4.1 ng/mL (P = 0.10). The mean proliferation index was 7.4 +/- 7.8 for the historic controls versus 5.0 +/- 4.9 for the diet-treated patients (P = 0.05). The distribution of the apoptotic indexes differed significantly (P = 0.01) between groups, with most historic controls exhibiting TUNEL categorical scores of 0; diet-treated patients largely exhibited scores of 1. Both the proliferation rate and apoptosis were significantly associated with the number of days on the diet (P = 0.049 and P = 0.017, respectively). CONCLUSIONS: These pilot data suggest that a flaxseed-supplemented, fat-restricted diet may affect prostate cancer biology and associated biomarkers. Further study is needed to determine the benefit of this dietary regimen as either a complementary or preventive therapy.\",\n \"title\": \"Pilot study of dietary fat restriction and flaxseed supplementation in men with prostate cancer before surgery: exploring the effects on hormonal l...\"\n },\n {\n \"docid\": \"MED-3237\",\n \"text\": \"The modern Western-type diet is deficient in fruits and vegetables and contains excessive animal products, generating the accumulation of non-metabolizable anions and a lifespan state of overlooked metabolic acidosis, whose magnitude increases progressively with aging due to the physiological decline in kidney function. In response to this state of diet-derived metabolic acidosis, the kidney implements compensating mechanisms aimed to restore the acid-base balance, such as the removal of the non-metabolizable anions, the conservation of citrate, and the enhancement of kidney ammoniagenesis and urinary excretion of ammonium ions. These adaptive processes lower the urine pH and induce an extensive change in urine composition, including hypocitraturia, hypercalciuria, and nitrogen and phosphate wasting. Low urine pH predisposes to uric acid stone formation. Hypocitraturia and hypercalciuria are risk factors for calcium stone disease. Even a very mild degree of metabolic acidosis induces skeletal muscle resistance to the insulin action and dietary acid load may be an important variable in predicting the metabolic abnormalities and the cardiovascular risk of the general population, the overweight and obese persons, and other patient populations including diabetes and chronic kidney failure. High dietary acid load is more likely to result in diabetes and systemic hypertension and may increase the cardiovascular risk. Results of recent observational studies confirm an association between insulin resistance and metabolic acidosis markers, including low serum bicarbonate, high serum anion gap, hypocitraturia, and low urine pH. Copyright © 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.\",\n \"title\": \"Diet-induced metabolic acidosis.\"\n },\n {\n \"docid\": \"MED-5116\",\n \"text\": \"BACKGROUND: Laboratory research and a growing number of epidemiologic studies have provided evidence for a reduced risk of breast cancer associated with dietary intake of certain classes of flavonoids. However, the effects of flavonoids on survival are not known. In a population-based cohort of breast cancer patients, we investigated whether dietary flavonoid intake before diagnosis is associated with subsequent survival. METHODS: Women ages 25 to 98 years who were newly diagnosed with a first primary invasive breast cancer between August 1, 1996, and July 31, 1997, and participated in a population-based, case-control study (n=1,210) were followed for vital status through December 31, 2002. At the case-control interview conducted shortly after diagnosis, respondents completed a FFQ that assessed dietary intake in the previous 12 months. All-cause mortality (n=173 deaths) and breast cancer-specific mortality (n=113 deaths) were determined through the National Death Index. RESULTS: Reduced hazard ratios [age- and energy-adjusted hazard ratio (95% confidence interval)] for all-cause mortality were observed among premenopausal and postmenopausal women for the highest quintile of intake, compared with the lowest, for flavones [0.63 (0.41-0.96)], isoflavones [0.52 (0.33-0.82)], and anthocyanidins [0.64 (0.42-0.98)]. No significant trends in risk were observed. Results were similar for breast cancer-specific mortality only. CONCLUSION: Mortality may be reduced in association with high levels of dietary flavones and isoflavones among postmenopausal U.S. breast cancer patients. Larger studies are needed to confirm our findings.\",\n \"title\": \"Dietary flavonoid intake and breast cancer survival among women on Long Island.\"\n },\n {\n \"docid\": \"MED-2502\",\n \"text\": \"Dietary restriction (DR) without malnutrition is widely regarded to be a universal mechanism for prolonging lifespan. It is generally believed that the benefits of DR arise from eating fewer calories (termed caloric restriction, CR). Here we argue that, rather than calories, the key determinant of the relationship between diet and longevity is the balance of protein to non-protein energy ingested. This ratio affects not only lifespan, but also total energy intake, metabolism, immunity and the likelihood of developing obesity and associated metabolic disorders. Among various possible mechanisms linking macronutrient balance to lifespan, the nexus between the TOR and AMPK signaling pathways is emerging as a central coordinator.\",\n \"title\": \"Macronutrient balance and lifespan\"\n },\n {\n \"docid\": \"MED-1227\",\n \"text\": \"To correct methodologic flaws (Type II error, confounding variables, and nonblinding) in previous studies relating infant feeding to later obesity, we conducted case-control studies of 639 patients 12 to 18 years of age attending our Adolescent Clinic, and 533 similarly aged healthy children attending a Montreal high school. Each subject was classified as either obese, overweight, or nonobese based on measurements of height, weight, and triceps and subscapular skinfolds. Feeding history, family history, and demographic data were later ascertained \\\"blindly\\\" by telephone interview. Analysis of the raw data revealed a significantly elevated estimated relative risk of not breast-feeding and a significant trend for rates of breast-feeding among the three weight groups. The magnitude of the protective effect appeared to rise slightly with increased duration of breast-feeding. Delayed introduction of solid foods provided little if any additional benefit. Several demographic and clinical variables proved to be confounding, but the significant protective effect of breast-feeding persisted even after controlling for confounders. We conclude that breast-feeding does protect against later obesity and attribute the conflicting results of previous studies to insufficient attention to methodologic standards.\",\n \"title\": \"Do breast-feeding and delayed introduction of solid foods protect against subsequent obesity?\"\n },\n {\n \"docid\": \"MED-4163\",\n \"text\": \"OBJECTIVE: The health benefits of vegetarian diets are well-recognized; however, long-term adherence to these diets may be associated with nutrient inadequacies, particularly vitamins B12 and D, calcium, iron, zinc, and protein. The dietary reference intakes (DRIs) expert panels recommended adjustments to the iron, zinc, and calcium DRIs for vegetarians to account for decreased bioavailability, but no adjustments were considered necessary for the protein DRI under the assumption that vegetarians consume about 50% of protein from animal (dairy/egg) sources. This study examined dietary protein sources in a convenience sample of 21 young adult vegetarian women who completed food logs on 4 consecutive days (3 weekdays and 1 weekend day). METHODS: The daily contribution percentages of protein consumed from cereals, legumes, nuts/seeds, fruits/vegetables, and dairy/egg were computed, and the protein digestibility corrected amino acid score of the daily diets was calculated. RESULTS: The calculated total dietary protein digestibility score for participants was 82 ± 1%, which differed significantly (P < 0.001) from the DRI reference score, 88%, and the 4-d average protein digestibility corrected amino acid score for the sample was 80 ± 2%, which also differed significantly (P < 0.001) from the DRI reference value, 100%. The analyses indicated that animal protein accounted for only 21% of dietary protein. CONCLUSION: This research suggests that the protein DRI for vegetarians consuming less than the expected amounts of animal protein (45% to 50% of total protein) may need to be adjusted from 0.8 to about 1.0 g/kg to account for decreased protein bioavailability. Copyright © 2011 Elsevier Inc. All rights reserved.\",\n \"title\": \"Protein dietary reference intakes may be inadequate for vegetarians if low amounts of animal protein are consumed.\"\n },\n {\n \"docid\": \"MED-2082\",\n \"text\": \"BACKGROUND: Reliable and timely information on the leading causes of death in populations, and how these are changing, is a crucial input into health policy debates. In the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010), we aimed to estimate annual deaths for the world and 21 regions between 1980 and 2010 for 235 causes, with uncertainty intervals (UIs), separately by age and sex. METHODS: We attempted to identify all available data on causes of death for 187 countries from 1980 to 2010 from vital registration, verbal autopsy, mortality surveillance, censuses, surveys, hospitals, police records, and mortuaries. We assessed data quality for completeness, diagnostic accuracy, missing data, stochastic variations, and probable causes of death. We applied six different modelling strategies to estimate cause-specific mortality trends depending on the strength of the data. For 133 causes and three special aggregates we used the Cause of Death Ensemble model (CODEm) approach, which uses four families of statistical models testing a large set of different models using different permutations of covariates. Model ensembles were developed from these component models. We assessed model performance with rigorous out-of-sample testing of prediction error and the validity of 95% UIs. For 13 causes with low observed numbers of deaths, we developed negative binomial models with plausible covariates. For 27 causes for which death is rare, we modelled the higher level cause in the cause hierarchy of the GBD 2010 and then allocated deaths across component causes proportionately, estimated from all available data in the database. For selected causes (African trypanosomiasis, congenital syphilis, whooping cough, measles, typhoid and parathyroid, leishmaniasis, acute hepatitis E, and HIV/AIDS), we used natural history models based on information on incidence, prevalence, and case-fatality. We separately estimated cause fractions by aetiology for diarrhoea, lower respiratory infections, and meningitis, as well as disaggregations by subcause for chronic kidney disease, maternal disorders, cirrhosis, and liver cancer. For deaths due to collective violence and natural disasters, we used mortality shock regressions. For every cause, we estimated 95% UIs that captured both parameter estimation uncertainty and uncertainty due to model specification where CODEm was used. We constrained cause-specific fractions within every age-sex group to sum to total mortality based on draws from the uncertainty distributions. FINDINGS: In 2010, there were 52·8 million deaths globally. At the most aggregate level, communicable, maternal, neonatal, and nutritional causes were 24·9% of deaths worldwide in 2010, down from 15·9 million (34·1%) of 46·5 million in 1990. This decrease was largely due to decreases in mortality from diarrhoeal disease (from 2·5 to 1·4 million), lower respiratory infections (from 3·4 to 2·8 million), neonatal disorders (from 3·1 to 2·2 million), measles (from 0·63 to 0·13 million), and tetanus (from 0·27 to 0·06 million). Deaths from HIV/AIDS increased from 0·30 million in 1990 to 1·5 million in 2010, reaching a peak of 1·7 million in 2006. Malaria mortality also rose by an estimated 19·9% since 1990 to 1·17 million deaths in 2010. Tuberculosis killed 1·2 million people in 2010. Deaths from non-communicable diseases rose by just under 8 million between 1990 and 2010, accounting for two of every three deaths (34·5 million) worldwide by 2010. 8 million people died from cancer in 2010, 38% more than two decades ago; of these, 1·5 million (19%) were from trachea, bronchus, and lung cancer. Ischaemic heart disease and stroke collectively killed 12·9 million people in 2010, or one in four deaths worldwide, compared with one in five in 1990; 1·3 million deaths were due to diabetes, twice as many as in 1990. The fraction of global deaths due to injuries (5·1 million deaths) was marginally higher in 2010 (9·6%) compared with two decades earlier (8·8%). This was driven by a 46% rise in deaths worldwide due to road traffic accidents (1·3 million in 2010) and a rise in deaths from falls. Ischaemic heart disease, stroke, chronic obstructive pulmonary disease (COPD), lower respiratory infections, lung cancer, and HIV/AIDS were the leading causes of death in 2010. Ischaemic heart disease, lower respiratory infections, stroke, diarrhoeal disease, malaria, and HIV/AIDS were the leading causes of years of life lost due to premature mortality (YLLs) in 2010, similar to what was estimated for 1990, except for HIV/AIDS and preterm birth complications. YLLs from lower respiratory infections and diarrhoea decreased by 45-54% since 1990; ischaemic heart disease and stroke YLLs increased by 17-28%. Regional variations in leading causes of death were substantial. Communicable, maternal, neonatal, and nutritional causes still accounted for 76% of premature mortality in sub-Saharan Africa in 2010. Age standardised death rates from some key disorders rose (HIV/AIDS, Alzheimer's disease, diabetes mellitus, and chronic kidney disease in particular), but for most diseases, death rates fell in the past two decades; including major vascular diseases, COPD, most forms of cancer, liver cirrhosis, and maternal disorders. For other conditions, notably malaria, prostate cancer, and injuries, little change was noted. INTERPRETATION: Population growth, increased average age of the world's population, and largely decreasing age-specific, sex-specific, and cause-specific death rates combine to drive a broad shift from communicable, maternal, neonatal, and nutritional causes towards non-communicable diseases. Nevertheless, communicable, maternal, neonatal, and nutritional causes remain the dominant causes of YLLs in sub-Saharan Africa. Overlaid on this general pattern of the epidemiological transition, marked regional variation exists in many causes, such as interpersonal violence, suicide, liver cancer, diabetes, cirrhosis, Chagas disease, African trypanosomiasis, melanoma, and others. Regional heterogeneity highlights the importance of sound epidemiological assessments of the causes of death on a regular basis. FUNDING: Bill & Melinda Gates Foundation. Copyright © 2012 Elsevier Ltd. All rights reserved.\",\n \"title\": \"Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease S...\"\n },\n {\n \"docid\": \"MED-5110\",\n \"text\": \"Americans consume billions of hotdogs per year resulting in more than a billion dollars in retail sales. Package labels typically list some type of meat as the primary ingredient. The purpose of this study is to assess the meat and water content of several hotdog brands to determine if the package labels are accurate. Eight brands of hotdogs were evaluated for water content by weight. A variety of routine techniques in surgical pathology including routine light microscopy with hematoxylin-eosin-stained sections, special staining, immunohistochemistry, and electron microscopy were used to assess for meat content and for other recognizable components. Package labels indicated that the top-listed ingredient in all 8 brands was meat; the second listed ingredient was water (n = 6) and another type of meat (n = 2). Water comprised 44% to 69% (median, 57%) of the total weight. Meat content determined by microscopic cross-section analysis ranged from 2.9% to 21.2% (median, 5.7%). The cost per hotdog ($0.12-$0.42) roughly correlated with meat content. A variety of tissues were observed besides skeletal muscle including bone (n = 8), collagen (n = 8), blood vessels (n = 8), plant material (n = 8), peripheral nerve (n = 7), adipose (n = 5), cartilage (n = 4), and skin (n = 1). Glial fibrillary acidic protein immunostaining was not observed in any of the hotdogs. Lipid content on oil red O staining was graded as moderate in 3 hotdogs and marked in 5 hotdogs. Electron microscopy showed recognizable skeletal muscle with evidence of degenerative changes. In conclusion, hotdog ingredient labels are misleading; most brands are more than 50% water by weight. The amount of meat (skeletal muscle) in most brands comprised less than 10% of the cross-sectional surface area. More expensive brands generally had more meat. All hotdogs contained other tissue types (bone and cartilage) not related to skeletal muscle; brain tissue was not present.\",\n \"title\": \"Applying morphologic techniques to evaluate hotdogs: what is in the hotdogs we eat?\"\n },\n {\n \"docid\": \"MED-3139\",\n \"text\": \"Background: Soy isoflavones have antiestrogenic and anticancer properties but also possess estrogen-like properties, which has raised concern about soy food consumption among breast cancer survivors. Objective: We prospectively evaluated the association between postdiagnosis soy food consumption and breast cancer outcomes among US and Chinese women by using data from the After Breast Cancer Pooling Project. Design: The analysis included 9514 breast cancer survivors with a diagnosis of invasive breast cancer between 1991 and 2006 from 2 US cohorts and 1 Chinese cohort. Soy isoflavone intake (mg/d) was measured with validated food-frequency questionnaires. HRs and 95% CIs were estimated by using delayed-entry Cox regression models, adjusted for sociodemographic, clinical, and lifestyle factors. Results: After a mean follow-up of 7.4 y, we identified 1171 total deaths (881 from breast cancer) and 1348 recurrences. Despite large differences in soy isoflavone intake by country, isoflavone consumption was inversely associated with recurrence among both US and Chinese women, regardless of whether data were analyzed separately by country or combined. No heterogeneity was observed. In the pooled analysis, consumption of ≥10 mg isoflavones/d was associated with a nonsignificant reduced risk of all-cause (HR: 0.87; 95% CI: 0.70, 1.10) and breast cancer–specific (HR: 0.83; 95% CI: 0.64, 1.07) mortality and a statistically significant reduced risk of recurrence (HR: 0.75; 95% CI: 0.61, 0.92). Conclusion: In this large study of combined data on US and Chinese women, postdiagnosis soy food consumption of ≥10 mg isoflavones/d was associated with a nonsignificant reduced risk of breast cancer–specific mortality and a statistically significant reduced risk of recurrence. One of the studies included in the After Breast Cancer Pooling Project, the Women's Healthy Eating & Living Study, was registered at clinicaltrials.gov as NCT00003787.\",\n \"title\": \"Soy food intake after diagnosis of breast cancer and survival: an in-depth analysis of combined evidence from cohort studies of US and Chinese women\"\n },\n {\n \"docid\": \"MED-4203\",\n \"text\": \"Oxygen is vital for most organisms but, paradoxically, damages key biological sites. Oxygenic threat is met by antioxidants that evolved in parallel with our oxygenic atmosphere. Plants employ antioxidants to defend their structures against reactive oxygen species (ROS; oxidants) produced during photosynthesis. The human body is exposed to these same oxidants, and we have also evolved an effective antioxidant system. However, this is not infallible. ROS breach defences, oxidative damage ensues, accumulates with age, and causes a variety of pathological changes. Plant-based, antioxidant-rich foods traditionally formed the major part of the human diet, and plant-based dietary antioxidants are hypothesized to have an important role in maintaining human health. This hypothesis is logical in evolutionary terms, especially when we consider the relatively hypoxic environment in which humans may have evolved. In this paper, the human diet is discussed briefly in terms of its evolutionary development, different strategies of antioxidant defence are outlined, and evolution of dietary antioxidants is discussed from the perspectives of plant need and our current dietary requirements. Finally, possibilities in regard to dietary antioxidants, evolution, and human health are presented, and an evolutionary cost-benefit analysis is presented in relation to why we lost the ability to make ascorbic acid (vitamin C) although we retained an absolute requirement for it.\",\n \"title\": \"Evolution of dietary antioxidants.\"\n },\n {\n \"docid\": \"MED-2352\",\n \"text\": \"BACKGROUND: Carbohydrate-specific IgE antibodies present on nonprimate mammalian proteins were incriminated recently in delayed meat anaphylaxis. The aim of this study was to explore whether anaphylaxis to mammalian kidney is also associated with galactose-α-1,3-galactose (αGal)-specific IgE. METHODS: Fourteen patients with anaphylaxis to pork or beef kidney underwent prick tests to meat and kidney. Some patients also underwent skin tests to Erbitux(®) (cetuximab). IgE antibodies to αGal, swine urine proteins, beef and pork meat, serum albumin proteins, cat, and rFel d 1 were measured by ImmunoCAP(®). The αGal levels were estimated in meats and kidney by ELISA inhibition assay. Cross-reactivity between αGal and pork kidney was studied with the ImmunoCAP(®) inhibition assay. RESULTS: Among the 14 patients, 12 presented with anaphylactic shock. Reactions occurred within 2 h from exposure in 67% of patients. Associated risk factors were observed in 10 cases, and alcohol was the main cofactor. Three patients underwent an oral challenge to pork kidney, and anaphylaxis occurred after ingestion of small quantities (1-2 g). Prick tests to kidney were positive in 54% of patients. All tested patients showed positive skin tests to Erbitux(®). All patients tested positive for IgE to αGal, with levels ranging from 0.4 to 294 kU/l. IgE binding to αGal was inhibited by raw pork kidney extract (mean, 77%; range, 55-87%), which showed a high amount of αGal determinants. CONCLUSIONS: Pork or beef kidney anaphylaxis is related to αGal IgE. Its peculiar severity could be due to an elevated content of αGal epitopes in kidney. © 2012 John Wiley & Sons A/S.\",\n \"title\": \"Anaphylaxis to pork kidney is related to IgE antibodies specific for galactose-alpha-1,3-galactose.\"\n },\n {\n \"docid\": \"MED-3129\",\n \"text\": \"BRCA1 mutations have been associated with hereditary breast cancer only. Recent studies indicate that a subgroup of sporadic breast cancer might also be associated with reduction in BRCA1 mRNA levels and protein expression. However, the mechanism of reduced mRNA and protein expression is yet not fully elucidated. This study aims to assess BRCA1 protein expression and the role of BRCA1 promoter methylation in sporadic breast cancer in North Indian population and to correlate these with known prognostic factors and molecular profiles of breast cancer. BRCA1 protein expression was normal (>50 % tumour cells) in 41 (43 %) cases, reduced (20-50 % tumour cells) in 33 (35 %) cases and absent/markedly reduced (<20 % tumour cells) in 21 (22.1 %) cases. Cases which were negative for BRCA1 protein were more frequently positive for basal markers (29 versus 5 %) and were more often ER-negative (62 versus 39 %) than BRCA1-positive tumours. Methylation of BRCA1 promoter region was seen in 11/45 cases (24 %). All 11 cases showing BRCA1 methylation had absent (eight cases) or reduced (three cases) BRCA1 protein expression. BRCA1 protein-negative tumours were more frequently basal marker-positive and ER-negative, highlighting the 'BRCAness' of sporadic breast cancer with loss of BRCA1 protein expression through promoter hypermethylation similar to hereditary breast cancer with BRCA1 mutations. Loss of BRCA1 in sporadic breast cancer suggests that therapeutics targeting BRCA1 pathway in hereditary breast cancer like PARP inhibitors might be used as therapeutic targets for sporadic breast tumours.\",\n \"title\": \"BRCA1-methylated sporadic breast cancers are BRCA-like in showing a basal phenotype and absence of ER expression.\"\n },\n {\n \"docid\": \"MED-2356\",\n \"text\": \"Background In 2009, we reported a novel form of delayed anaphylaxis to red meat, which is related to serum IgE antibodies to the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal). Most of these patients had tolerated meat for many years previously. The implication is that some exposure in adult life had stimulated the production of these IgE antibodies. Objectives To investigate possible causes of this IgE antibody response, focusing on evidence related to tick bites, which are common in the region where these reactions occur. Methods Serum assays were carried out using biotinylated proteins and extracts bound to a streptavidin ImmunoCAP. Results Prospective studies on IgE antibodies in three subjects following tick bites showed an increase in IgE to alpha-gal of twenty-fold or greater. Other evidence included i) a strong correlation between histories of tick bites and IgE to alpha-gal (χ2=26.8, p<0.001), ii) evidence that these IgE antibodies are common in areas where the tick Amblyomma americanum is common, and iii) a significant correlation between IgE antibodies to alpha-gal and IgE antibodies to proteins derived from A. americanum (rs=0.75, p<0.001). Conclusion The results presented here provide evidence that tick bites are a cause, or possibly the only cause, of IgE specific for alpha-gal in this area of the United States. Both the number of subjects becoming sensitized and the titer of IgE antibodies to alpha-gal are striking. Here we report the first example of a response to an ectoparasite giving rise to an important form of food allergy.\",\n \"title\": \"The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose\"\n },\n {\n \"docid\": \"MED-4212\",\n \"text\": \"Soya foods may protect against the development of breast cancer. Insulin-like growth factor (IGF)-1 is under investigation as a possible link between nutrition and cancer. We examined the effect of soya foods on circulating IGF-1 and IGF binding protein (BP)-3 levels among 196 healthy premenopausal women in a 2-year randomised nutritional trial. The intervention group consumed two daily servings of soya foods including tofu, soya milk, soya nuts and soya protein powder (equivalent to 50 mg isoflavones and 5-22 g soya protein per serving); the controls maintained their regular diet. Five serum samples at baseline, 3, 6, 12, and 24 months were collected in the morning during the luteal phase and analysed for IGF-1 and IGFBP-3 by double-antibody ELISA. We applied mixed models to investigate the intervention effect and predictors of serum levels while considering the repeated measurement design. Adherence with the study regimen was high and dropout rates were acceptable. Randomisation resulted in similar mean IGF-1 and IGFBP-3 levels by group. We did not observe a significant intervention effect on IGF-1, IGFBP-3, and their molar ratio during the entire study period. However, urinary isoflavone excretion during the study period was positively associated with IGF-1 (P=0.04) and the IGF-1:IGFBP-3 ratio (P=0.06). The effect was consistent over time. Adding soya foods to the diet of premenopausal women does not appear to lower serum levels of IGF-1 and IGFBP-3; if anything, the greater protein intake from soya may lead to a small increase in IGF-1 serum levels.\",\n \"title\": \"Insulin-like growth factor-1 and binding protein-3 in a 2-year soya intervention among premenopausal women.\"\n },\n {\n \"docid\": \"MED-3245\",\n \"text\": \"Cruciferous vegetables, tomato sauce, and legumes have been associated with reduced risk of incident advanced prostate cancer. In vitro and animal studies suggest these foods may inhibit progression of prostate cancer, but there are limited data in men. Therefore, we prospectively examined whether intake of total vegetables, and specifically cruciferous vegetables, tomato sauce, and legumes, after diagnosis reduce risk of prostate cancer progression among 1,560 men diagnosed with non-metastatic prostate cancer and participating in the Cancer of the Prostate Strategic Urologic Research Endeavor, a United States prostate cancer registry. As a secondary analysis, we also examined other vegetable sub-groups, total fruit, and subgroups of fruits. The participants were diagnosed primarily at community-based clinics and followed from 2004–2009. We assessed vegetable and fruit intake via a semi-quantitative food frequency questionnaire, and ascertained prostate cancer outcomes via urologist report and medical records. We observed 134 events of progression (53 biochemical recurrences, 71 secondary treatments likely due to recurrence, six bone metastases, four prostate cancer deaths) during 3,171 person-yrs. Men in the fourth quartile of post-diagnostic cruciferous vegetable intake had a statistically significant 59% decreased risk of prostate cancer progression compared to men in the lowest quartile (hazard ratio (HR): 0.41; 95% confidence interval (CI): 0.22, 0.76; p-trend: 0.003). No other vegetable or fruit group was statistically significantly associated with risk of prostate cancer progression. In conclusion, cruciferous vegetable intake after diagnosis may reduce risk of prostate cancer progression.\",\n \"title\": \"Vegetable and fruit intake after diagnosis and risk of prostate cancer progression\"\n },\n {\n \"docid\": \"MED-1723\",\n \"text\": \"The lower rates of some cancers in Asian countries than in Western countries may be partly because of diet, although the mechanisms are unknown. The aim of this cross-sectional study was to determine whether a plant-based (vegan) diet is associated with a lower circulating level of insulin-like growth factor I (IGF-I) compared with a meat-eating or lacto-ovo-vegetarian diet among 292 British women, ages 20-70 years. The mean serum IGF-I concentration was 13% lower in 92 vegan women compared with 99 meat-eaters and 101 vegetarians (P = 0.0006). The mean concentrations of both serum IGF-binding protein (IGFBP)-1 and IGFBP-2 were 20-40% higher in vegan women compared with meat-eaters and vegetarians (P = 0.005 and P = 0.0008 for IGFBP-1 and IGFBP-2, respectively). There were no significant differences in IGFBP-3, C-peptide, or sex hormone-binding globulin concentrations between the diet groups. Intake of protein rich in essential amino acids was positively associated with serum IGF-I (Pearson partial correlation coefficient; r = 0.27; P < 0.0001) and explained most of the differences in IGF-I concentration between the diet groups. These data suggest that a plant-based diet is associated with lower circulating levels of total IGF-I and higher levels of IGFBP-1 and IGFBP-2.\",\n \"title\": \"The associations of diet with serum insulin-like growth factor I and its main binding proteins in 292 women meat-eaters, vegetarians, and vegans.\"\n },\n {\n \"docid\": \"MED-4053\",\n \"text\": \"Heterocyclic amines (HCAs), potent mutagens and a risk factor for human cancers, are produced in meats cooked at high temperature. The aim of this study was to determine the HCA content in cooked meat products (beef, chicken, pork, fish) prepared by various cooking methods (pan frying, oven broiling, and oven baking at 170 to 230°C) that are preferred by U.S. meat consumers. The primary HCAs in these samples were PhIP (2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine) (1.49-10.89ng/g), MeIQx (2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline) (not detected-4.0ng/g), and DiMeIQx (2-amino-3,4,8-trimethyl-imidazo [4,5-f]quinoxaline) (not detected-3.57ng/g). Type and content of HCAs in cooked meat samples were highly dependent on cooking conditions. The total HCA content in well-done meat was 3.5 times higher than that of medium-rare meat. Fried pork (13.91ng/g) had higher levels of total HCAs than fried beef (8.92ng/g) and fried chicken (7.00ng/g). Among the samples, fried bacon contained the highest total HCA content (17.59ng/g). Copyright © 2011 Elsevier Ltd. All rights reserved.\",\n \"title\": \"Occurrence of heterocyclic amines in cooked meat products.\"\n },\n {\n \"docid\": \"MED-2450\",\n \"text\": \"Background Atopy is not uncommon among children living in rural Crete, but wheeze and rhinitis are rare. A study was undertaken to examine whether this discrepancy could be attributed to a high consumption of fresh fruit and vegetables or adherence to a traditional Mediterranean diet. Methods A cross‐sectional survey was performed in 690 children aged 7–18 years in rural Crete. Parents completed a questionnaire on their child's respiratory and allergic symptoms and a 58‐item food frequency questionnaire. Adherence to a Mediterranean diet was measured using a scale with 12 dietary items. Children underwent skin prick tests with 10 common aeroallergens. Results 80% of children ate fresh fruit (and 68% vegetables) at least twice a day. The intake of grapes, oranges, apples, and fresh tomatoes—the main local products in Crete—had no association with atopy but was protective for wheezing and rhinitis. A high consumption of nuts was found to be inversely associated with wheezing (OR 0.46; 95% CI 0.20 to 0.98), whereas margarine increased the risk of both wheeze (OR 2.19; 95% CI 1.01 to 4.82) and allergic rhinitis (OR 2.10; 95% CI 1.31 to 3.37). A high level of adherence to the Mediterranean diet was protective for allergic rhinitis (OR 0.34; 95% CI 0.18 to 0.64) while a more modest protection was observed for wheezing and atopy. Conclusion The results of this study suggest a beneficial effect of commonly consumed fruits, vegetables and nuts, and of a high adherence to a traditional Mediterranean diet during childhood on symptoms of asthma and rhinitis. Diet may explain the relative lack of allergic symptoms in this population.\",\n \"title\": \"Protective effect of fruits, vegetables and the Mediterranean diet on asthma and allergies among children in Crete\"\n },\n {\n \"docid\": \"MED-2295\",\n \"text\": \"BACKGROUND: Intake of dietary fiber has been recommended for many years as part of the guidelines from the American Heart Association, the Institute of Medicine, and other groups. The recommended Adequate Intake for dietary fiber for adults is 25 to 38 g/day (14 g/1,000 kcal/day). OBJECTIVE: To determine the average daily intake of dietary fiber among adults during the past decade and, specifically, to document progress toward national goals. DESIGN: Cross-sectional weighted data from the National Health and Nutrition Examination Survey among adults aged 18 years and older. PARTICIPANTS/SETTING: Data were collected from noninstitutionalized adults aged 18 years and older using a nationally representative, complex, multistage, probability-based survey of people living in the United States that was conducted by the National Center for Health Statistics. MAIN OUTCOME MEASURES: Daily dietary fiber intake by members of the US population based on 2-year groupings of the continuous survey from 1999 to 2008. RESULTS: Mean daily dietary fiber intake for 1999-2000 was 15.6 g/day, for 2001-2002 intake was 16.1g/day, for 2003-2004 intake was 15.5 g/day, for 2005-2006 intake was 15.8 g/day, and for 2007-2008 intake was 15.9 g/day. Participants with obesity (body mass index ≥30) consistently reported lower fiber intake than did individuals with normal weight or overweight (14.6 to 15.4 g/day and 15.6 to 16.8 g/day, respectively; P<0.0001). Mexican Americans had significantly higher intake in 1999-2000 than non-Hispanic whites (18.0 vs 16.1g/day; P<0.05), but Mexican Americans' intake did not increase over time (17.7 g/day in 2007-2008). Non-Hispanic blacks had fiber intake of 12.5 g/day at baseline that increased modestly to 13.1 g/day by 2007-2008. CONCLUSIONS: Daily fiber intake generally has not progressed toward national goals during the past decade, but there are some differences according to health and social factors. Additional clinical practice and public health strategies are needed. Copyright © 2012 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.\",\n \"title\": \"Trends in dietary fiber intake in the United States, 1999-2008.\"\n },\n {\n \"docid\": \"MED-4305\",\n \"text\": \"Influence of diet composition on mood during weight-reducing diets was studied in healthy young women of normal weight. A broad range of macronutrient intake was achieved by means of divergent dietary instructions for the composition of a 1,000 kcal per day diet adhered to for six weeks. Global mood during the last three weeks of the diet was significantly better in the \\\"vegetarian\\\" than in the \\\"mixed\\\" diet group. During this time a significant correlation was observed between relative carbohydrate intake and global mood (r = -0.74; p less than 0.01) and between the ratio of plasma tryptophan to other large neutral amino acids (a predictor of tryptophan flow into brain) and global mood (r = -0.52; p less than 0.05). Results suggest that group differences are related to differences in carbohydrate intake. It is hypothesized that impairment of central serotonergic function due to reduced tryptophan availability can prompt mood deterioration in situations of relatively low carbohydrate intake.\",\n \"title\": \"Macronutrient intake, plasma large neutral amino acids and mood during weight-reducing diets.\"\n },\n {\n \"docid\": \"MED-2658\",\n \"text\": \"The prevalence of allergic diseases has increased in recent decades. Allergic diseases, particularly asthma, are complex diseases with strong gene-environment interactions. Epidemiological studies have identified a variety of risk factors for the development of allergic diseases. Among them, endocrine-disrupting chemicals (EDCs) play an important role in triggering or exacerbating these diseases. 4-Nonylphenol (NP) and 4-octylphenol (OP)--two major alkylphenols--have been recognized as common toxic and xenobiotic endocrine disrupters. Due to their low solubility, high hydrophobicity, and low estrogenic activity, they tend to accumulate in the human body and may be associated with the adverse effects of allergic diseases. Recently, new evidence has supported the importance of alkylphenols in the in vitro allergic response. This review focuses on the effects of alkylphenols on several key cell types in the context of allergic inflammation. Copyright © 2012. Published by Elsevier B.V.\",\n \"title\": \"Alkylphenols--potential modulators of the allergic response.\"\n },\n {\n \"docid\": \"MED-2511\",\n \"text\": \"Residents of Okinawa, the southernmost prefecture of Japan, are known for their long average life expectancy, high numbers of centenarians, and accompanying low risk of age-associated diseases. Much of the longevity advantage in Okinawa is thought to be related to a healthy lifestyle, particularly the traditional diet, which is low in calories yet nutritionally dense, especially with regard to phytonutrients in the form of antioxidants and flavonoids. Research suggests that diets associated with a reduced risk of chronic diseases are similar to the traditional Okinawan diet, that is, vegetable and fruit heavy (therefore phytonutrient and antioxidant rich) but reduced in meat, refined grains, saturated fat, sugar, salt, and full-fat dairy products. Many of the characteristics of the diet in Okinawa are shared with other healthy dietary patterns, such as the traditional Mediterranean diet or the modern DASH (Dietary Approaches to Stop Hypertension) diet. Features such as the low levels of saturated fat, high antioxidant intake, and low glycemic load in these diets are likely contributing to a decreased risk for cardiovascular disease, some cancers, and other chronic diseases through multiple mechanisms, including reduced oxidative stress. A comparison of the nutrient profiles of the three dietary patterns shows that the traditional Okinawan diet is the lowest in fat intake, particularly in terms of saturated fat, and highest in carbohydrate intake, in keeping with the very high intake of antioxidant-rich yet calorie-poor orange-yellow root vegetables, such as sweet potatoes, and green leafy vegetables. Deeper analyses of the individual components of the Okinawan diet reveal that many of the traditional foods, herbs, or spices consumed on a regular basis could be labeled \\\"functional foods\\\" and, indeed, are currently being explored for their potential health-enhancing properties.\",\n \"title\": \"The Okinawan diet: health implications of a low-calorie, nutrient-dense, antioxidant-rich dietary pattern low in glycemic load.\"\n },\n {\n \"docid\": \"MED-1714\",\n \"text\": \"BACKGROUND: Western diets, obesity, and sedentary lifestyles are associated with increased cancer risk. The mechanisms responsible for this increased risk, however, are not clear. OBJECTIVE: We hypothesized that long-term low protein, low calorie intake and endurance exercise are associated with low concentrations of plasma growth factors and hormones that are linked to an increased risk of cancer. DESIGN: Plasma growth factors and hormones were evaluated in 21 sedentary subjects, who had been eating a low-protein, low-calorie diet for 4.4 +/- 2.8 y (x +/- SD age: 53.0 +/- 11 y); 21 endurance runners matched by body mass index (BMI; in kg/m2); and 21 age- and sex-matched sedentary subjects eating Western diets. RESULTS: BMI was lower in the low-protein, low-calorie diet (21.3 +/- 3.1) and runner (21.6 +/- 1.6) groups than in the Western diet (26.5 +/- 2.7; P < 0.005) group. Plasma concentrations of insulin, free sex hormones, leptin, and C-reactive protein were lower and sex hormone-binding globulin was higher in the low-protein, low-calorie diet and runner groups than in the sedentary Western diet group (all P < 0.05). Plasma insulin-like growth factor I (IGF-I) and the concentration ratio of IGF-I to IGF binding protein 3 were lower in the low-protein, low-calorie diet group (139 +/- 37 ng/mL and 0.033 +/- 0.01, respectively) than in the runner (177 +/- 37 ng/mL and 0.044 +/- 0.01, respectively) and sedentary Western (201 +/- 42 ng/mL and 0.046 +/- 0.01, respectively) diet groups (P < 0.005). CONCLUSIONS: Exercise training, decreased adiposity, and long-term consumption of a low-protein, low-calorie diet are associated with low plasma growth factors and hormones that are linked to an increased risk of cancer. Low protein intake may have additional protective effects because it is associated with a decrease in circulating IGF-I independent of body fat mass.\",\n \"title\": \"Long-term low-protein, low-calorie diet and endurance exercise modulate metabolic factors associated with cancer risk.\"\n },\n {\n \"docid\": \"MED-3929\",\n \"text\": \"Objective: To prospectively examine whether higher intakes of total flavonoids and their subclasses (flavanones, anthocyanins, flavan-3-ols, flavonols, flavones, and polymers) were associated with a lower risk of developing Parkinson disease (PD). Methods: In the current analysis, we included 49,281 men in the Health Professional Follow-up Study and 80,336 women from the Nurses' Health Study. Five major sources of flavonoid-rich foods (tea, berry fruits, apples, red wine, and orange/orange juice) were also examined. Flavonoid intake was assessed using an updated food composition database and a validated food frequency questionnaire. Results: We identified 805 participants (438 men and 367 women) who developed PD during 20–22 years of follow-up. In men, after adjusting for multiple confounders, participants in the highest quintile of total flavonoids had a 40%lower PD risk than those in the lowest quintile (hazard ratio [HR] = 0.60; 95% confidence interval 0.43, 0.83; p trend = 0.001). No significant relationship was observed in women (p trend = 0.62) or in pooled analyses (p trend = 0.23). In the pooled analyses for the subclasses, intakes of anthocyanins and a rich dietary source, berries, were significantly associated with a lower PD risk (HR comparing 2 extreme intake quintiles were 0.76 for anthocyanins and 0.77 for berries, respectively; p trend < 0.02 for both). Conclusions: Our findings suggest that intake of some flavonoids may reduce PD risk, particularly in men, but a protective effect of other constituents of plant foods cannot be excluded.\",\n \"title\": \"Habitual intake of dietary flavonoids and risk of Parkinson disease\"\n },\n {\n \"docid\": \"MED-2278\",\n \"text\": \"OBJECTIVES: To investigate the anti-inflammatory and anti-oxidative effects of anthocyanins from cherries on Freund's adjuvant-induced arthritis (AIA) in rats. METHODS: Arthritis was induced intradermally by injection with 0.1 mL of complete Freund's adjuvant (CFA) into the right hind footpad of male Sprague Dawley (SD) rats. Anthocyanins at 40, 20 and 10 mg/kg (body weight) were administered orally to the treated rats for 28 days after the injection. Tumour necrosis factor-alpha (TNFalpha) in serum and prostaglandin E2 (PGE2) in paws were assayed by radioimmunoassay (RIA), and anti-oxidative effects was assayed by measuring total anti-oxidative capacity (T-AOC), superoxide dismutase (SOD) and malondialdehyde (MDA) in serum. RESULTS: Anthocyanins at 40 mg/kg significantly decreased the levels of TNFalpha in serum and PGE2 in paws, simultaneously improving the anti-oxidative status of AIA. We found that at this dosage T-AOC was potentized, the activity of SOD increased and the level of MDA in serum decreased. However, anthocyanins at 20 and 10 mg/kg had less effect on the inflammatory factors and anti-oxidative capacity of AIA. CONCLUSIONS: Anthocyanins have potential anti-inflammatory and anti-oxidative effects on AIA.\",\n \"title\": \"Anti-inflammatory and anti-oxidative effects of cherries on Freund's adjuvant-induced arthritis in rats.\"\n },\n {\n \"docid\": \"MED-1616\",\n \"text\": \"The role of very-low-carbohydrate ketogenic diets (VLCKD) in the long-term management of obesity is not well established. The present meta-analysis aimed to investigate whether individuals assigned to a VLCKD (i.e. a diet with no more than 50 g carbohydrates/d) achieve better long-term body weight and cardiovascular risk factor management when compared with individuals assigned to a conventional low-fat diet (LFD; i.e. a restricted-energy diet with less than 30% of energy from fat). Through August 2012, MEDLINE, CENTRAL, ScienceDirect,Scopus, LILACS, SciELO, ClinicalTrials.gov and grey literature databases were searched, using no date or language restrictions, for randomised controlled trials that assigned adults to a VLCKD or a LFD, with 12 months or more of follow-up. The primary outcome was bodyweight. The secondary outcomes were TAG, HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), systolic and diastolic blood pressure,glucose, insulin, HbA1c and C-reactive protein levels. A total of thirteen studies met the inclusion/exclusion criteria. In the overall analysis,five outcomes revealed significant results. Individuals assigned to a VLCKD showed decreased body weight (weighted mean difference 20·91 (95% CI 21·65, 20·17) kg, 1415 patients), TAG (weighted mean difference 20·18 (95% CI 20·27, 20·08) mmol/l, 1258 patients)and diastolic blood pressure (weighted mean difference 21·43 (95% CI 22·49, 20·37) mmHg, 1298 patients) while increased HDL-C(weighted mean difference 0·09 (95% CI 0·06, 0·12) mmol/l, 1257 patients) and LDL-C (weighted mean difference 0·12 (95% CI 0·04,0·2) mmol/l, 1255 patients). Individuals assigned to a VLCKD achieve a greater weight loss than those assigned to a LFD in the longterm; hence, a VLCKD may be an alternative tool against obesity.\",\n \"title\": \"Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss: a meta-analysis of randomised controlled trials.\"\n },\n {\n \"docid\": \"MED-4556\",\n \"text\": \"Tolerable upper intake levels (ULs) set by the Institute of Medicine (IOM) are important, in part because they are used for estimating the percentage of the population at potential risk of adverse effects from excessive nutrient intake. The IOM did not set ULs for trans fat, saturated fat, and cholesterol because any intake level above 0% of energy increased LDL cholesterol concentration and these three food components are unavoidable in ordinary diets. The purpose of the analysis presented in this review was to evaluate clinical trial and prospective observational data that were not previously considered for setting a UL with the aim of determining whether the current UL model could be used for saturated fat, trans fat, and cholesterol. The results of this analysis confirm the limitations of the risk assessment model for setting ULs because of its inability to identify a UL for food components, such as cholesterol, that lack an intake threshold associated with increased chronic disease risk. © 2011 International Life Sciences Institute.\",\n \"title\": \"Tolerable upper intake levels for trans fat, saturated fat, and cholesterol.\"\n },\n {\n \"docid\": \"MED-2461\",\n \"text\": \"This study aimed to evaluate the association of diet with respiratory symptoms and asthma in schoolchildren in Taipei, Taiwan. An in-class interview survey elicited experiences of asthma and respiratory symptoms and consumption frequencies of the major food categories in 2290 fifth graders. Respiratory symptoms surveyed included persistent cough, chest tightness, wheezing with cold, wheezing without cold, dyspnea-associated wheezing, and exercise-induced cough or wheezing. Results showed that the consumption of sweetened beverages had the strongest association with respiratory symptoms and was positively associated with six of the seven respiratory symptoms (all p < 0.05). The adjusted odds ratios (aOR) ranged from 1.05 (95% confidence interval (CI = 1.01-1.09) for exercise-induced cough to 1.09 (95% CI = 1.03-1.16) for wheezing without cold. Egg consumption was associated with 5 of the 7 respiratory symptoms. Consumptions of seafood, soy products, and fruits were each negatively associated with one of the seven respiratory symptoms (all p < 0.05). Consumption of seafood was negatively associated with physician-diagnosed asthma and consumptions of sweetened beverages and eggs were positively associated with suspected asthma (p < 0.05). In conclusion, the study suggests that diet is associated with the respiratory symptoms in schoolchildren in Taipei. Consumptions of sweetened beverages and eggs are associated with increased risk of respiratory symptoms and asthma whereas consumptions of soy products and fruits are associated with reduced risk of respiratory symptoms.\",\n \"title\": \"The association of diet with respiratory symptoms and asthma in schoolchildren in Taipei, Taiwan.\"\n },\n {\n \"docid\": \"MED-2591\",\n \"text\": \"Low-carbohydrate diets have become increasingly popular for weight loss. Although they may improve some metabolic markers, particularly in type 2 diabetes mellitus (T2D) or the metabolic syndrome (MS), their net effect on arterial wall function remains unclear. The objective was to evaluate the relation between dietary macronutrient composition and the small artery reactive hyperaemia index (saRHI), a marker of small artery endothelial function, in a cohort of patients at increased cardiovascular (CV) risk. The present cross-sectional study included 247 patients. Diet was evaluated by a 3-d food-intake register and reduced to a novel low-carbohydrate diet score (LCDS). Physical examination, demographic, biochemical and anthropometry parameters were recorded, and the saRHI was measured in each patient. Individuals in the lowest LCDS quartile (Q1, 45 % carbohydrate; 20 % protein; 32 % fat) had higher saRHI values than those in the top quartile (Q4, 29 % carbohydrate, 24 % protein, 40 % fat; 1.66 (sd 0.41) v. 1.52 (sd 0.22), P= 0.037). These results were particularly strong in patients with the MS (Q1 = 1.82 (sd 0.32) v. Q4 = 1.61 (sd 027); P= 0.021) and T2D (Q1 = 1.78 (sd 0.31) v. Q4 = 1.62 (sd 0.35); P= 0.011). Multivariate analysis demonstrated that individuals in the highest LCDS quartile had a significantly negative coefficient of saRHI, which was independent of confounders (OR -0.85; 95 % CI 0.19, 0.92; P= 0.031). These findings suggest that a dietary pattern characterised by a low amount of carbohydrate, but high amounts of protein and fat, is associated with a poorer small artery vascular reactivity in patients with increased CV risk.\",\n \"title\": \"Negative effect of a low-carbohydrate, high-protein, high-fat diet on small peripheral artery reactivity in patients with increased cardiovascular ...\"\n },\n {\n \"docid\": \"MED-1184\",\n \"text\": \"It has been shown that feces of patients with ulcerative colitis uniformly contain sulfate reducing bacteria. Sulfide produced by these bacteria interferes with butyrate-dependent energy metabolism of cultured colonocytes and may be involved in the pathogenesis of ulcerative colitis. Mucosal biopsies from the sigmoid rectum of 10 patients (no caner, polyps, inflammatory bowel disease) were incubated with either NaCl, sodium hydrogen sulfide (1 mmol/L), a combination of both sodium hydrogen sulfide and butyrate (10 mmol/L), or butyrate. Mucosal proliferation was assessed by bromodeoxyuridine labeling of cells in S-phase. Compared to NaCl, sulfide increased the labeling of the entire crypt significantly, by 19% (p < 0.05). This effect was due to an expansion of the proliferative zone to the upper crypt (compartments 3-5), where the increase in proliferation was 54%. Sulfide-induced hyperproliferation was reversed when samples were coincubated with sulfide and butyrate. The study shows that sodium hydrogen sulfide induces mucosal hyperproliferation. Our data support a possible role of sulfide in the pathogenesis of UC and confirm the role of butyrate in the regulation of colonic proliferation and in the treatment of UC.\",\n \"title\": \"Antagonistic effects of sulfide and butyrate on proliferation of colonic mucosa: a potential role for these agents in the pathogenesis of ulcerativ...\"\n },\n {\n \"docid\": \"MED-4976\",\n \"text\": \"Airborne cooking by-products from frying beef (hamburgers), pork (bacon strips) and soybean-based food (tempeh burgers) were collected, extracted, tested for mutagenicity and chemically analysed. The fumes generated by frying pork and beef were mutagenic, with 4900 and 1300 revertants/g of food cooked, respectively. No mutagenicity was detected in fumes from frying tempeh burgers. Bacon fried to a well-done but non-charred state was eight times more mutagenic in a microsuspension Ames/Salmonella test (TA98 with S-9) than hamburgers and about 350 times more mutagenic than tempeh burgers. Among food samples cooked to a well-done, non-charred state, bacon strips had almost 15-fold more mass (109.5 ng/g) than that of the beef, whereas no heterocyclic amine (HCA) was detected in the fried tempeh burgers. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was the most abundant HCA, followed by 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx). No 2-amino-9H-pyrido[2,3-b]indole (A alpha C) was detected in the food samples fried at about 200 degrees C, although it was present in the collected airborne products. The total amounts of HCAs in the smoke condensates were 3 ng/g from fried bacon, 0.37 ng/g from fried beef and 0.177 ng/g from fried soy-based food. This study indicates that cooks are potentially exposed to relatively high levels of airborne mutagens and carcinogens and that long-term sampling inside restaurants and kitchens may be warranted in order to assess the potential risk of prolonged exposure.\",\n \"title\": \"Airborne mutagens produced by frying beef, pork and a soy-based food.\"\n },\n {\n \"docid\": \"MED-4216\",\n \"text\": \"High levels of insulin-like growth factor 1 (IGF-1) are associated with increased risk of prostate cancer, whereas increased levels of some of its binding proteins (IGFBPs) seem to be protective. High intakes of dietary protein, especially animal and soy protein, appear to increase IGF-1. However, soy isoflavones have demonstrated anti-proliferative and apoptotic effects both in vitro and in vivo. We evaluated dietary intakes of total protein and soy isoflavones in relation to the IGF axis in prostate cancer patients making comprehensive lifestyle changes including a very low-fat vegan diet supplemented with soy protein (58 g/day). After one year, intervention group patients reported significantly higher intakes of dietary protein and soy isoflavones compared to usual-care controls (P < 0.001). IGF-1 increased significantly in both groups, whereas IGFBP-1 rose in the experimental group only (P < 0.01). Increases in vegetable protein over one year were associated with increases in IGFBP-1 among intervention group patients (P < 0.05). These results suggest that dietary protein and soy isoflavones, in the context of comprehensive lifestyle changes, may not significantly alter IGF-1. However, given the recent literature indicating that high intake of protein rich in essential amino acids (animal or soy protein) may increase IGF-1, it may be prudent for men with early stage prostate cancer not to exceed dietary protein recommendations.\",\n \"title\": \"Relationship of dietary protein and soy isoflavones to serum IGF-1 and IGF binding proteins in the Prostate Cancer Lifestyle Trial.\"\n },\n {\n \"docid\": \"MED-4600\",\n \"text\": \"Enough solid evidence now exists to offer women several fundamental strategies for healthy eating. They include emphasizing healthful unsaturated fats, whole grains, good protein “packages,” and fruits and vegetables; limiting consumption of trans and saturated fats, highly refined grains, and sugary beverages; and taking a multivitamin with folic acid and extra vitamin D as a nutritional safety net. A diet based on these principles is healthy through virtually all life stages, from young adulthood through planning for pregnancy, pregnancy, and on into old age.\",\n \"title\": \"Essentials of Healthy Eating: A Guide\"\n },\n {\n \"docid\": \"MED-3001\",\n \"text\": \"Over the last three decades, the concept of Western disease has become well established. Medicine has approached this group of diseases by searching for new cures but has achieved relatively little success. We argue that medicine should now accept the failure of this strategy and place a major emphasis on prevention. The key objective is to change the climate of opinion so that prevention is taken seriously by the general population. The chief activity should be a wide ranging public education campaign so as to persuade people to live a healthier lifestyle. Medicine will require restructuring in order to carry out this work. Medical education needs to be reformed so that medical students receive the necessary training. This must be done as part of an integrated approach in which government, industry and medical research all play a major role. Governments should use taxation and subsidies in areas such as food and tobacco so as to shift consumption patterns towards healthier products. Governments must also tighten laws on tobacco sales and advertising, support health education, and improve food labelling. Industry must be made far more responsive to the health needs of the population. This should be done both by public education, so as to alter demand, and by government action. Medical research should change its emphasis from studying the detailed mechanisms of disease (\\\"complex research\\\") to studying the role of lifestyle factors (\\\"simple research\\\").\",\n \"title\": \"Towards a new system of health: the challenge of Western disease.\"\n },\n {\n \"docid\": \"MED-2202\",\n \"text\": \"The overall objective of this chapter is to review the past, present, and future role of the sweet potato (Ipomoea batatas [L.] Lam) in human nutrition. Specifically, the chapter describes the role of the sweet potato in human diets; outlines the biochemical and nutritional composition of the sweet potato with emphasis on its beta-carotene and anthocyanin contents; highlights sweet potato utilization, and its potential as value-added products in human food systems; and demonstrates the potential of the sweet potato in the African context. Early records have indicated that the sweet potato is a staple food source for many indigenous populations in Central and South Americas, Ryukyu Island, Africa, the Caribbean, the Maori people, Hawaiians, and Papua New Guineans. Protein contents of sweet potato leaves and roots range from 4.0% to 27.0% and 1.0% to 9.0%, respectively. The sweet potato could be considered as an excellent novel source of natural health-promoting compounds, such as beta-carotene and anthocyanins, for the functional food market. Also, the high concentration of anthocyanin and beta-carotene in sweet potato, combined with the high stability of the color extract make it a promising and healthier alternative to synthetic coloring agents in food systems. Starch and flour processing from sweet potato can create new economic and employment activities for farmers and rural households, and can add nutritional value to food systems. Repositioning sweet potato production and its potential for value-added products will contribute substantially to utilizing its benefits and many uses in human food systems. Multidisciplinary, integrated research and development activities aimed at improving production, storage, postharvest and processing technologies, and quality of the sweet potato and its potential value-added products are critical issues, which should be addressed globally.\",\n \"title\": \"Sweet potato: a review of its past, present, and future role in human nutrition.\"\n },\n {\n \"docid\": \"MED-1612\",\n \"text\": \"Type II diabetic subjects were given 50 g protein, 50 g glucose, or 50 g glucose with 50 g protein as a single meal in random sequence. The plasma glucose and insulin response was determined over the subsequent 5 h. The plasma glucose area above the baseline following a glucose meal was reduced 34% when protein was given with the glucose. When protein was given alone, the glucose concentration remained stable for 2 h and then declined. The insulin area following glucose was only modestly greater than with a protein meal (97 +/- 35, 83 +/- 19 microU X h/ml, respectively). When glucose was given with protein, the mean insulin area was considerably greater than when glucose or protein was given alone (247 +/- 33 microU X h/ml). When various amounts of protein were given with 50 g glucose, the insulin area response was essentially first order. Subsequently, subjects were given 50 g glucose or 50 g glucose with 50 g protein as two meals 4 h apart in random sequence. The insulin areas were not significantly different for each meal but were higher when protein + glucose was given. After the second glucose meal the plasma glucose area was 33% less than after the first meal. Following the second glucose + protein meal the plasma glucose area was markedly reduced, being only 7% as large as after the first meal. These data indicate that protein given with glucose will increase insulin secretion and reduce the plasma glucose rise in at least some type II diabetic persons.\",\n \"title\": \"Effect of protein ingestion on the glucose and insulin response to a standardized oral glucose load.\"\n },\n {\n \"docid\": \"MED-2505\",\n \"text\": \"BACKGROUND: Relative risk estimates suggest that effective implementation of behaviors commonly advocated in preventive medicine should increase life expectancy, although there is little direct evidence. OBJECTIVE: To test the hypothesis that choices regarding diet, exercise, and smoking influence life expectancy. METHODS: A total of 34 192 California Seventh-Day Adventists (75% of those eligible) were enrolled in a cohort and followed up from 1976 to 1988. A mailed questionnaire provided dietary and other exposure information at study baseline. Mortality for all subjects was ascertained by matching to state death tapes and the National Death Index. RESULTS: California Adventists have higher life expectancies at the age of 30 years than other white Californians by 7.28 years (95% confidence interval, 6.59-7.97 years) in men and by 4.42 years (95% confidence interval, 3.96-4.88 years) in women, giving them perhaps the highest life expectancy of any formally described population. Commonly observed combinations of diet, exercise, body mass index, past smoking habits, and hormone replacement therapy (in women) can account for differences of up to 10 years of life expectancy among Adventists. A comparison of life expectancy when these factors take high-risk compared with low-risk values shows independent effects that vary between 1.06 and 2.74 years for different variables. The effect of each variable is assessed with all others at either medium- or high-risk levels. CONCLUSIONS: Choices regarding diet, exercise, cigarette smoking, body weight, and hormone replacement therapy, in combination, appear to change life expectancy by many years. The longevity experience of Adventists probably demonstrates the beneficial effects of more optimal behaviors.\",\n \"title\": \"Ten years of life: Is it a matter of choice?\"\n },\n {\n \"docid\": \"MED-3305\",\n \"text\": \"BACKGROUND AND AIM: The occurrence of malignant pleural mesothelioma (MPM) has been reported among population groups with no documented professional exposure to asbestos fibres living in different geographic areas. This paper reviews existing data related to non occupational MPM including its occurrence in the province of Catania (Sicily, Italy). METHODS: An electronic search of literature related to non occupational MPM was performed including the year 2005. RESULTS: Non occupational MPM in subjects living in areas contaminated by a variety of asbestos and non asbestos fibres has been well documented through a number of epidemiologic studies including cases series, case-control studies, and a cohort study. In addition, the observation of familial clustering of MPM, suggests that genetic factors may play a role in the pathogenesis of this malignancy. The epidemiological evidence also suggests that MPM may occur as a result of the interaction between environmental carcinogens, genetic factors, and virus infection. CONCLUSION: It is likely that genetic predisposition and non-occupational exposure to low doses of asbestos and asbestos-like fibres may concur to the development of malignant mesothelioma. However, additional epidemiological and laboratory studies are needed to further understand the relationship between environmental exposure and individual susceptibility to this malignancy.\",\n \"title\": \"Non-occupational malignant pleural mesothelioma due to asbestos and non-asbestos fibres.\"\n },\n {\n \"docid\": \"MED-3454\",\n \"text\": \"To determine if 6 weeks of supplementation with antioxidants could alleviate exercise-induced DNA damage, we studied 21 runners during a 50 km ultramarathon. Subjects were randomly assigned to one of two groups: (1) placebos (PL) or (2) antioxidants (AO) (1000 mg vitamin C and 400 IU RRR-alpha-tocopheryl acetate). The comet assay was used to assess DNA damage in circulating leukocytes at selected time points: pre-, mid-, and 2 h postrace and daily for 6 days postrace. All subjects completed the race: run time 7.1 +/- 0.1 h, energy expenditure 5008 +/- 80 kcal for women (n = 10) and 6932 +/- 206 kcal for men (n = 11). Overall, the percentage DNA damage increased at midrace (p <.02), but returned to baseline by 2 h postrace, indicating that the exercise bout induced nonpersistent DNA damage. There was a gender x treatment x time interaction (p <.01). One day postrace, women taking AO had 62% less DNA damage than women taking PL (p <.0008). In contrast, there were no statistically significant differences between the two treatment groups of men at any time point. Thus, endurance exercise resulted in DNA damage as shown by the comet assay and AO seemed to enhance recovery in women but not in men.\",\n \"title\": \"Endurance exercise results in DNA damage as detected by the comet assay.\"\n },\n {\n \"docid\": \"MED-3783\",\n \"text\": \"Fish odour syndrome (trimethylaminuria) is a metabolic syndrome caused by abnormal excretion of trimethylamine in the breath, urine, sweat, saliva and vaginal secretions. Trimethylamine is derived from the intestinal bacterial degradation of foods rich in choline and carnitine and is normally oxidised by the liver to odourless trimethylamine N-oxide which is then excreted in the urine. Impaired oxidation of trimethylamine is thought to be the cause of the fish odour syndrome and is responsible for the smell of rotting fish. Certain foods rich in choline exacerbate the condition and the patients have a variety of psychological problems. Recognition of the condition is important as dietary adjustments reduce the excretion of trimethylamine and may reduce the odour. Occasionally, a short course of metronidazole, neomycin and lactulose may suppress production of trimethylamine by reducing the activity of gut microflora. Keywords: fish odour syndrome; trimethylaminuria\",\n \"title\": \"Fish odour syndrome\"\n },\n {\n \"docid\": \"MED-4055\",\n \"text\": \"Heterocyclic amines (HCAs) are formed when meat products such as beef, chicken, pork and fish are cooked at high temperatures. The most abundant HCA found in the human diet is 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP). PhIP causes mammary carcinomas in female rats and mice, and is associated with an increased risk of developing colon, breast, and prostate cancer in humans. PhIP is metabolized by cytochrome P-450s producing N-OH-PhIP. The N-OH-PhIP can be esterified by phase II enzymes forming an arylnitrenium ion that binds to DNA causing adducts. Furthermore, N-OH-PhIP may be reduced by cytochrome b5 reductase producing superoxide anions and hydroxyl radicals causing DNA strand breaks. Diallyl sulfide (DAS) has been shown to prevent cancer in several animal models, presumably by metabolic modulation. We hypothesize that PhIP produces reactive oxygen species causing DNA strand breaks and that DAS will inhibit the formation of PhIP induced DNA strand breaks. To test this hypothesis we treated normal breast epithelial (MCF-10A) cells with PhIP, DAS and a combination of PhIP and DAS. The detection of lipid peroxides was used as a surrogate for ROS. Lipid peroxides were detected using a PeroxiDetect kit (Sigma). PhIP increased the production of lipid peroxides and DAS decreased the PhIP-induced peroxidation by 47%. To determine if PhIP causes DNA strand breaks in MCF-10A cells, cells were treated for 3, 6, 9, and 24 h with PhIP (100 microM), DAS (100 microM) and a combination of PhIP (100 microM) and DAS (100 microM). DNA strand breaks were evaluated using the Comet assay. PhIP produced DNA strand breaks in a dose- and time-dependent fashion. We have shown that DAS inhibits PhIP-induced DNA strand breaks by inhibiting the production of reactive oxygen species. Therefore, we propose that DAS can prevent PhIP-induced breast cancer.\",\n \"title\": \"Diallyl sulfide inhibits PhIP-induced DNA strand breaks in normal human breast epithelial cells.\"\n },\n {\n \"docid\": \"MED-5186\",\n \"text\": \"We evaluated the role of dietary nutrients in the etiology of endometrial cancer in a population-based case-control study of 1,204 newly diagnosed endometrial cancer cases and 1,212 age frequency-matched controls. Information on usual dietary habits was collected during an in-person interview using a validated, quantitative food frequency questionnaire. Logistic regression analysis was conducted to evaluate the association of nutrients with endometrial cancer risk using an energy density method (e.g., nutrient intake/1,000 kilocalories of intake). Higher energy intake was associated with increased risk, which was attributable to animal source energy and a high proportion of energy from protein and fat. Odds ratios comparing highest versus lowest quintiles of intake were elevated for intake of animal protein (Odds ratio (OR) 5 2.0, 95% confidential interval: 1.5–2.7) and fat (OR 5 1.5, 1.2–2.0), but reduced for plant sources of these nutrients (OR 5 0.7, 0.5–0.9 for protein and OR 5 0.6, 0.5–0.8 for fat). Further analysis showed that saturated and monounsaturated fat intake was associated with elevated risk, while polyunsaturated fat intake was unrelated to risk. Dietary retinol, β-carotene, vitamin C, vitamin E, fiber, and vitamin supplements were inversely associated with risk. No significant association was observed for dietary vitamin B1 or vitamin B2. Our findings suggest that associations of dietary macronutrients with endometrial cancer risk may depend on their sources, with intake of animal origin nutrients being related to higher risk and intake of plant origin nutrients related to lower risk. Dietary fiber, retinol, β-carotene, vitamin C, vitamin E, and vitamin supplementation may decrease the risk of endometrial cancer.\",\n \"title\": \"Nutritional factors in relation to endometrial cancer: A report from a population-based case-control study in Shanghai, China\"\n },\n {\n \"docid\": \"MED-3193\",\n \"text\": \"Background Multiple Myeloma (MM) is a B cell neoplasm causing lytic or osteopenic bone abnormalities. Whole body skeletal survey (WBSS), Magnetic resonance (MR) and 18F-FDG PET/CT are imaging techniques routinely used for the evaluation of bone involvement in MM patients. Aim As MM bone lesions may present low 18F-FDG uptake; the aim of this study was to assess the possible added value and limitations of 11C-Choline to that of 18F-FDG PET/CT in patients affected with MM. Methods Ten patients affected with MM underwent a standard 11C-Choline PET/CT and an 18F-FDG PET/CT within one week. The results of the two scans were compared in terms of number, sites and SUVmax of lesions. Results Four patients (40%) had a negative concordant 11C-Choline and 18F-FDG PET/CT scans. Two patients (20%) had a positive 11C-Choline and 18F-FDG PET/CT scans that identified the same number and sites of bone lesions. The remaining four patients (40%) had a positive 11C-Choline and 18F-FDG PET/CT scan, but the two exams identified different number of lesions. Choline showed a mean SUVmax of 5 while FDG showed a mean SUVmax of 3.8 (P = 0.042). Overall, 11C-Choline PET/CT scans detected 37 bone lesions and 18F-FDG PET/CT scans detected 22 bone lesions but the difference was not significant (P = 0.8). Conclusion According to these preliminary data, 11C-Choline PET/CT appears to be more sensitive than 18F-FDG PET/CT for the detection of bony myelomatous lesions. If these data are confirmed in larger series of patients, 11C-Choline may be considered a more appropriate functional imaging in association with MRI for MM bone staging.\",\n \"title\": \"11C-choline vs. 18F-FDG PET/CT in assessing bone involvement in patients with multiple myeloma\"\n },\n {\n \"docid\": \"MED-2519\",\n \"text\": \"To date, the only intervention that has consistently been shown to slow the rate of aging, and to increase mean and maximum lifespan in short-lived species, is life-long calorie restriction. It is yet unclear whether long-term calorie restriction in longer lived species (i.e. primates and humans) will have a similar effect. In humans, several studies investigating short-term calorie restriction or \\\"weight loss\\\" programs suggest beneficial outcomes on parameters of cardiovascular disease. Studies on long-term calorie restriction are performed on a self-selected group of human subjects and show similar effects. However, few studies are currently investigating the quality of life and potential pitfalls of long-term calorie restriction in humans. It is likely that some of the physiological and psychological effects of caloric restriction that occur in animals may impact the human life very differently. For certain, calorie restriction has a plethora of health benefits in mammals, such as a reduction in age-related diseases such as cancer. However, despite the \\\"magic\\\" of CR, this intervention in humans may present itself with a number of health concerns, which may not be applicable to or impact the life of experimental animals, but may do so in humans. These potential pitfalls and \\\"side effects\\\" are not clearly addressed in the literature and will be a focus of this review.\",\n \"title\": \"Caloric restriction in humans: potential pitfalls and health concerns.\"\n },\n {\n \"docid\": \"MED-2296\",\n \"text\": \"This study aimed to investigate health belief as a major motive for diet and lifestyle behaviors of 100 vegans in the United States; and to determine congruence with selected health and nutrition outcomes. Response data from an administered questionnaire was analyzed. Statistical analyses determined the most common factors influencing diet choice; the number of vegans practicing particular lifestyle behaviors; body mass index; and prevalence of self-reported chronic disease diagnoses. Nutrient intakes were analyzed and assessed against Dietary Reference Intakes. Health was the most reported reason for diet choice (47%). In the health belief, animal welfare, and religious/other motive categories, low percentages of chronic disease diagnoses were reported: 27%, 11%, and 15%, respectively. There were no significant differences in health behaviors and indices among vegan motive categories, except for product fat content choices. Within the entire study population, health-related vegan motive coincided with regular exercise; 71% normal BMI (mean=22.6); minimal alcohol and smoking practices; frequently consumed vegetables, nuts, and grains; healthy choices in meal types, cooking methods, and low-fat product consumption; and adequate intakes for most protective nutrients when compared to reference values. But incongruence was found with 0% intake adequacy for vitamin D; and observation of excessive sodium use. Copyright © 2013 Elsevier Ltd. All rights reserved.\",\n \"title\": \"Vegan lifestyle behaviors: an exploration of congruence with health-related beliefs and assessed health indices.\"\n },\n {\n \"docid\": \"MED-2659\",\n \"text\": \"U.S. and European regulators and researchers disagree over risks of a common class of surfactants.\",\n \"title\": \"European bans on surfactant trigger transatlantic debate.\"\n },\n {\n \"docid\": \"MED-3132\",\n \"text\": \"Little is known about dietitians current practice in counselling clients about the use of legumes in a low fat, high fibre diet. An exploratory e-mail questionnaire was sent to members of Dietitians of Canada to assess: dietitian use and preferences for legumes, dietitian practice, opinions about clients attitudes and preferences, and resource needs. Counsellors (n=256) had high personal use of legumes (64% > or = 1 serving/week) and frequently recommended legumes in counselling. The legumes most preferred by respondents and their clients were: peanuts, kidney beans, split peas, chickpeas, and lentils. Respondents often recommended canned bean products (76%) and tofu (61%), but other legume grocery products were less often recommended. The most common client issues identified were: flatulence (87% agreed), lack of familiarity (85%), and knowledge of preparation (82%). Dietitians were not satisfied with current resources to support practice, especially those respondents providing primarily clinical counselling services. The most requested resources were: recipes (90%), pamphlets (82%), food demonstrations (75%) and Internet sites (63%). Client level research is now needed to confirm the importance of the issues identified and to develop and test strategies for legume promotion in counselling.\",\n \"title\": \"Legume promotion in counselling: an e-mail survey of dietitians.\"\n },\n {\n \"docid\": \"MED-2453\",\n \"text\": \"BACKGROUND: Fresh fruit consumption and vitamin C intake have been associated with improved lung function in adults. Whether this is due to enhancement of lung growth, to a reduction in lung function decline, or to protection against bronchospasm is unclear. METHODS: In a cross- sectional school based survey of 2650 children aged 8-11 from 10 towns in England and Wales the main outcome measure was forced expiratory volume in one second (FEV1) standardised for body size and sex. Exposure was assessed by a food frequency questionnaire to parents and by measurement of plasma levels of vitamin C in a subsample of 278 children. RESULTS: FEV1 was positively associated with frequency of fresh fruit consumption. After adjustment for possible confounding variables including social class and passive smoking, those who never ate any fresh fruit had an estimated FEV1 some 79 ml (4.3%) lower than those who ate these items more than once a day (95% CI 22 to 136 ml). The association between FEV1 and fruit consumption was stronger in subjects with wheeze than in non-wheezers (p = 0.020 for difference in trend), though wheeze itself was not related to fresh fruit consumption. Frequency of consumption of salads and of green vegetables were both associated with FEV1 but the relationships were weaker than for fresh fruit. Plasma vitamin C levels were unrelated to FEV1 (r = - 0.01, p = 0.92) or to wheeze and were only weakly related to fresh fruit consumption (r = 0.13, p = 0.055). CONCLUSIONS: Fresh fruit consumption appears to have a beneficial effect on lung function in children. Further work is needed to confirm whether the effect is restricted to subjects who wheeze and to identify the specific nutrient involved.\",\n \"title\": \"Effect of fresh fruit consumption on lung function and wheeze in children\"\n },\n {\n \"docid\": \"MED-2476\",\n \"text\": \"An increase in asthma and atopic disease has been recorded in many countries where society has become more prosperous. We have investigated two possible explanations: a reduction in childhood infections and a change in diet. In a cohort of people followed up since 1964, originally selected as a random sample of primary school children, we have investigated the relevance of family size and the common childhood infectious diseases to development of eczema, hay fever and asthma. Although membership of a large family reduced risks of hay fever and eczema (but not asthma), this was not explained by the infections the child had suffered. Indeed, the more infections the child had had, the greater the likelihood of asthma, although measles gave a modest measure of protection. We have investigated dietary factors in two separate studies. In the first, we have shown the risks of bronchial hyper-reactivity are increased seven-fold among those with the lowest intake of vitamin C, while the lowest intake of saturated fats gave a 10-fold protection. In the second, we have shown that the risk of adult-onset wheezy illness is increased five-fold by the lowest intake of vitamin E and doubled by the lowest intake of vitamin C. These results were supported by direct measurements of the vitamins and triglycerides in plasma. We have proposed that changes in the diet of pregnant women may have reflected those observed in the population as a whole and that these may have resulted in the birth of cohorts of children predisposed to atopy and asthma. The direct test of this is to study the diet and nutritional status of a large cohort of pregnant women and to follow their offspring forward. This is our current research.\",\n \"title\": \"Diet, infection and wheezy illness: lessons from adults.\"\n },\n {\n \"docid\": \"MED-2475\",\n \"text\": \"Current understanding of the use of exclusion diets in the management of asthma in children is limited and controversial. The aim of this study was to examine the effects of excluding eggs and milk on the occurrence of symptoms in children with asthma and involved 22 children aged between three and 14 years clinically diagnosed as having mild to moderate disease. The investigation was single blind and prospective, and parents were given the option of volunteering to join the 'experiment' group, avoiding eggs, milk and their products for eight weeks, or the 'control' group, who consumed their customary food. Thirteen children were recruited to the experimental group and nine to the control group. A trained paediatrician at the beginning and end of the study period assessed the children. A seven-day assessment of food intake was made before, during and immediately after the period of dietary intervention in both groups. A blood sample was taken from each child for determination of food specific antibodies and in those children who could do so, the peak expiratory flow rate (PEFR) was measured. Based on the recommended nutrient intake (RNI), the mean percentage energy intake of the children in the experimental group was significantly lower (p < 0.05) in the experimental group. After the eight-week study period and compared with baseline values, the mean serum anti-ovalbumin IgG and anti-beta lactoglobulin IgG concentrations were statistically significantly reduced (p < 0.05) for both in the experimental group. In contrast, the values for anti-ovalbumin IgG in the control group were significantly increased and those for anti-beta lactoglobulin IgG were practically unchanged. The total IgE values were unchanged in both groups. Over the study period, the PEFR in those children in the experimental group able to perform the test was significantly increased, but no such change was noted in the children in the control group who could do the test. These results suggest that even over the short time period of eight weeks, an egg- and milk-free diet can reduce atopic symptoms and improve lung function in asthmatic children.\",\n \"title\": \"The effects of exclusion of dietary egg and milk in the management of asthmatic children: a pilot study.\"\n },\n {\n \"docid\": \"MED-1716\",\n \"text\": \"Obesity has reached epidemic proportions in the developed world. The progression from obesity to diabetes mellitus type 2, via metabolic syndrome, is recognised, and the significant associated increase in the risk of major human cancers acknowledged. We review the molecular basis of the involvement of morbidly high concentrations of endogenous or therapeutic insulin and of insulin-like growth factors in the progression from obesity to diabetes and finally to cancer. Epidemiological and biochemical studies establish the role of insulin and hyperinsulinaemia in cancer risk and progression. Insulin-like growth factors, IGF-1 and IGF-2, secreted by visceral or mammary adipose tissue have significant paracrine and endocrine effects. These effects can be exacerbated by increased steroid hormone production. Structural studies elucidate how each of the three ligands, insulin, IGF-1, and IGF-2, interacts differently with isoforms A and B of the insulin receptor and with type I IGF receptor and explain how these protagonists contribute to diabetes-associated cancer. The above should inform appropriate treatment of cancers that arise in obese individuals and in those with diabetes mellitus type 2. Novel drugs that target the insulin and insulin-like growth factor signal transduction pathways are in clinical trial and should be effective if appropriate biomarker-informed patient stratification is implemented.\",\n \"title\": \"A Twenty-First Century Cancer Epidemic Caused by Obesity: The Involvement of Insulin, Diabetes, and Insulin-Like Growth Factors\"\n },\n {\n \"docid\": \"MED-3216\",\n \"text\": \"Increasing dietary protein results in an increase in urinary calcium. Despite over 80 y of research, the source of the additional urinary calcium remains unclear. Because most calcium balance studies found little effect of dietary protein on intestinal calcium absorption, it was assumed that the skeleton was the source of the calcium. The hypothesis was that the high endogenous acid load generated by a protein-rich diet would increase bone resorption and skeletal fracture. However, there are no definitive nutrition intervention studies that show a detrimental effect of a high protein diet on the skeleton and the hypothesis remains unproven. Recent studies from our laboratory demonstrate that dietary protein affects intestinal calcium absorption. We conducted a series of short-term nutrition intervention trials in healthy adults where dietary protein was adjusted to either low, medium or high. The highest protein diet resulted in hypercalciuria with no change in serum parathyroid hormone. Surprisingly, within 4 d, the low protein diet induced secondary hyperparathyroidism that persisted for 2 wk. The secondary hyperparathyroidism induced by the low protein diet was attributed to a reduction in intestinal calcium absorption (as assessed by dual stable calcium isotopes). The long-term consequences of these low protein-induced changes in calcium metabolism are not known, but they could be detrimental to skeletal health. Several recent epidemiological studies demonstrate reduced bone density and increased rates of bone loss in individuals habitually consuming low protein diets. Therefore, studies are needed to determine whether low protein intakes directly affect rates of bone resorption, bone formation or both.\",\n \"title\": \"Low protein intake: the impact on calcium and bone homeostasis in humans.\"\n },\n {\n \"docid\": \"MED-3236\",\n \"text\": \"A first objective of the present study was to estimate the acid-base balance of the food intake in vegetarians and non-vegetarians. A second objective was to evaluate if additional input of specific food items on the existing potential renal acid load (PRAL) list was necessary for the comparison of the two dietary patterns. Thirty vegetarians between the age of 18 and 30 years were matched for sex, age and BMI with 30 non-vegetarians. Based on the 3-days food diaries the acid-base status of the food intake was estimated using the PRAL method. Mean PRAL values as estimated with the standard table yielded an alkaline load of -5.4 +/- 14.4 mEq/d in the vegetarians compared to an acid load of 10.3 +/- 14.4 mEq/d in the nonvegetarians (p<0.001). Mean PRAL values as estimated with the extended table yielded an alkaline load of -10.9 +/-19.7 mEq/d in the vegetarians compared to an acid load of 13.8 +/- 17.1 mEq/d for the non-vegetarians (p<0.001). The findings of this study indicate that vegetarian food intake produces more alkaline outcomes compared to non-vegetarian diets. The use of the standard PRAL table was sufficient for discrimination between the two diets.\",\n \"title\": \"Nutrient based estimation of acid-base balance in vegetarians and non-vegetarians.\"\n },\n {\n \"docid\": \"MED-3315\",\n \"text\": \"PURPOSE: To test the hypothesis that exposure to poultry oncogenic viruses that widely occurs occupationally in poultry workers and in the general population, may be associated with increased risks of deaths from liver and pancreatic cancers, and to identify new risk factors. METHODS: A pilot case-cohort study of both cancers within a combined cohort of 30,411 highly exposed poultry workers and 16,408 control subjects was conducted, and risk assessed by logistic regression odds ratios (OR) and proportional hazards risk ratios. RESULTS: New occupational findings were recorded respectively for pancreatic/liver cancers, for slaughtering of poultry (OR = 8.9, 95% confidence interval [CI]: 2.7-29.3)/OR = 9.1, 95% CI: 1.9-42.9); catching of live chickens (OR = 3.6, 95% CI: 1.2-10.9)/OR = 1.0, 95% CI: 0.1-8.5); killing other types of animals for food (OR = 4.8, 95% CI: 1.5-16.6)/OR = 2.0, 95% CI: 0.2-18.2), and ever worked on a pig raising farm (OR = 3.0, 95% CI: 1.0-8.2) for pancreatic cancer only. New non-occupational findings for liver cancer were for receiving immunization with yellow fever vaccine (OR = 8.7, 95% CI: 1.0-76.3); and vaccination with typhoid vaccine (OR = 6.3, 95% CI: 1.1-37.4). The study also confirmed previously reported risk factors for both diseases. CONCLUSIONS: This study provides preliminary evidence that exposure to poultry oncogenic viruses may possibly be associated with the occurrence of liver and pancreatic cancers. Case-control studies nested within occupational cohorts of highly exposed subjects of sufficient statistical power may provide an efficient and valid method of investigating/confirming these findings. Copyright © 2011 Elsevier Inc. All rights reserved.\",\n \"title\": \"A pilot case-cohort study of liver and pancreatic cancers in poultry workers.\"\n },\n {\n \"docid\": \"MED-3358\",\n \"text\": \"BACKGROUND & AIMS: Taste sensitivity to fatty acids influences food ingestion and may regulate fat intake and body weight status. Fatty acids are detected via homologous receptors within the mouth and gastrointestinal (GI) tract, where attenuated sensitivity may be associated with greater fat intake and BMI. This study aimed to extend observations surrounding fatty acid taste, specifically the types of foods consumed and dietary behaviours that may be associated with fatty acid taste sensitivity. METHODS: 51 subjects (41 female; BMI, 21.4 ± 0.46 kg/m², age, 20 ± 0.52 yrs, 10 male; BMI, 23.6 ± 1.4 kg/m², age, 22 ± 1 yrs) were screened for oral sensitivity to oleic acid (3.8 mM) using triplicate sensory evaluations, and classified as hypersensitive; (3/3 correct identifications), or hyposensitive, (<3/3). Fat-taste perception (using sensory-matched custards made with 0, 2, 6, 10% oil), recent diet (4-day diet record) and food habits and behaviours (food habits and behaviours questionnaire) were also established. RESULTS: 75% (n = 38) of subjects were classified as hyposensitive to oleic acid and these subjects differed from those who were classified as hypersensitive. Hyposensitive subjects consumed significantly more energy, fat, saturated fat, fatty foods (butter, meat, dairy), had greater BMI and were less perceptive of small changes in the fat content of custard (all P < 0.05), compared to hypersensitive subjects. CONCLUSION: An inability to perceive low concentrations of fatty acids in foods was associated with greater consumption of fatty foods, specifically butter, meat, dairy, and increasing BMI. 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.\",\n \"title\": \"Oral sensitivity to oleic acid is associated with fat intake and body mass index.\"\n },\n {\n \"docid\": \"MED-3780\",\n \"text\": \"Metabolomics studies hold promise for discovery of pathways linked to disease processes. Cardiovascular disease (CVD) represents the leading cause of death and morbidity worldwide. A metabolomics approach was used to generate unbiased small molecule metabolic profiles in plasma that predict risk for CVD. Three metabolites of the dietary lipid phosphatidylcholine, namely choline, trimethylamine N-oxide (TMAO), and betaine, were identified and then shown to predict risk for CVD in an independent large clinical cohort. Dietary supplementation of mice with choline, TMAO or betaine promoted up-regulation of multiple macrophage scavenger receptors linked to atherosclerosis, and supplementation with choline or TMAO promoted atherosclerosis. Studies using germ-free mice confirmed a critical role for dietary choline and gut flora in TMAO production, augmented macrophage cholesterol accumulation and foam cell formation. Suppression of intestinal microflora in atherosclerosis-prone mice inhibited dietary choline-enhanced atherosclerosis. Genetic variations controlling expression of flavin monooxygenases (FMOs), an enzymatic source of TMAO, segregated with atherosclerosis in hyperlipidemic mice. Discovery of a relationship between gut flora-dependent metabolism of dietary phosphatidylcholine and CVD pathogenesis provides opportunities for development of both novel diagnostic tests and therapeutic approaches for atherosclerotic heart disease.\",\n \"title\": \"Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease\"\n },\n {\n \"docid\": \"MED-3227\",\n \"text\": \"Although high-protein diets induce hypercalciuria in humans, the source of the additional urinary calcium remains unclear. One hypothesis is that the high endogenous acid load of a high-protein diet is partially buffered by bone, leading to increased skeletal resorption and hypercalciuria. We used dual stable calcium isotopes to quantify the effect of a high-protein diet on calcium kinetics in women. The study consisted of 2 wk of a lead-in, well-balanced diet followed by 10 d of an experimental diet containing either moderate (1.0 g/kg) or high (2.1 g/kg) protein. Thirteen healthy women received both levels of protein in random order. Intestinal calcium absorption increased during the high-protein diet in comparison with the moderate (26.2 +/- 1.9% vs. 18.5 +/- 1.6%, P < 0.0001, mean +/- sem) as did urinary calcium (5.23 +/- 0.37 vs. 3.57 +/- 0.35 mmol/d, P < 0.0001, mean +/- sem). The high-protein diet caused a significant reduction in the fraction of urinary calcium of bone origin and a nonsignificant trend toward a reduction in the rate of bone turnover. There were no protein-induced effects on net bone balance. These data directly demonstrate that, at least in the short term, high-protein diets are not detrimental to bone.\",\n \"title\": \"The impact of dietary protein on calcium absorption and kinetic measures of bone turnover in women.\"\n },\n {\n \"docid\": \"MED-3352\",\n \"text\": \"The popularity of low- and reduced-fat foods has increased as consumers seek to decrease their energy consumption. Fat replacers may be used in fat-reduced products to maintain their sensory properties. However, these ingredients have been largely formulated to replicate nongustatory properties of fats to foods and have only achieved moderate success. There is increasing evidence that fats also activate the taste system and uniquely evoke responses that may influence product acceptance. Work supporting a taste component of fat has prompted questions about whether fat constitutes an additional \\\"primary\\\" or \\\"basic\\\" taste quality. This review briefly summarizes this evidence, focusing on human studies, when possible. Effective stimuli, possible receptors, and physiological changes due to oral fat exposure are discussed. Some studies suggest that there are fatty acid tasters and nontasters and if verified could have implications for targeted product development. © 2011 Institute of Food Technologists®\",\n \"title\": \"Are free fatty acids effective taste stimuli in humans? Presented at the symposium \\\"The Taste for Fat: New Discoveries on the Role of Fat in Sensor...\"\n },\n {\n \"docid\": \"MED-3138\",\n \"text\": \"Background Many consumers avoid eating beans because they believe legume consumption will cause excessive intestinal gas or flatulence. An increasing body of research and the 2010 Dietary Guidelines for Americans supports the benefits of a plant-based diet, and legumes specifically, in the reduction of chronic disease risks. The purpose of the current research was to investigate the perception of increased flatulence and gastrointestinal discomfort among participants who consumed a ½ cup of beans daily for 8 or 12 weeks. Methods Participants in three studies to test the effects of beans on heart disease biomarkers completed the same weekly questionnaire to assess gastrointestinal discomfort issues such as increased flatulence, stool changes, and bloating. Studies 1 and 2 were randomized crossover trials. Participants consumed ½ cup of pinto beans, black-eyed peas, and canned carrots as control (n = 17) in Study 1 for three randomized 8-week phases. For Study 2, participants ate ½ cup baked beans or canned carrots as control (n = 29) for two randomized 8-week phases. Study 3 was a parallel arm trial with 40 subjects receiving ½ cup pinto beans and 40 consuming a control soup for 12 weeks. Changes in the frequency of perceived flatulence, stool characteristics, and bloating were the primary outcome measures. Chi-square distributions were examined for the presence or absence of symptoms and demographic characteristics to determine differences by gender, age, body mass index (BMI), and bean type. Results Less than 50% reported increased flatulence from eating pinto or baked beans during the first week of each trial, but only 19% had a flatulence increase with black-eyed peas. A small percentage (3-11%) reported increased flatulence across the three studies even on control diets without flatulence-producing components. Conclusions People's concerns about excessive flatulence from eating beans may be exaggerated. Public health nutritionists should address the potential for gastrointestinal discomfort when increasing fiber intake from beans with clients. It is important to recognize there is individual variation in response to different bean types.\",\n \"title\": \"Perceptions of flatulence from bean consumption among adults in 3 feeding studies\"\n },\n {\n \"docid\": \"MED-3140\",\n \"text\": \"To identify protective dietary predictors amongst long-lived elderly people (N= 785), the \\\"Food Habits in Later Life \\\"(FHILL) study was undertaken among five cohorts in Japan, Sweden, Greece and Australia. Between 1988 and 1991, baseline data on food intakes were collected. There were 785 participants aged 70 and over that were followed up to seven years. Based on an alternative Cox Proportional Hazard model adjusted to age at enrollment (in 5-year intervals), gender and smoking, the legume food group showed 7-8% reduction in mortality hazard ratio for every 20g increase in daily intake with or without controlling for ethnicity (RR 0.92; 95% CI 0.85-0.99 and RR 0.93; 95% CI 0.87-0.99, respectively). Other food groups were not found to be consistently significant in predicting survival amongst the FHILL cohorts.\",\n \"title\": \"Legumes: the most important dietary predictor of survival in older people of different ethnicities.\"\n },\n {\n \"docid\": \"MED-2200\",\n \"text\": \"Cancer of the gallbladder is rare but fatal, and has an unusual geographic and demographic distribution. Gallstones and obesity have been suggested as possible risk factors. As diet is known to influence both these factors, we carried out the present study to evaluate the possible role of diet in gallbladder carcinogenesis. A case-control study involving 64 newly diagnosed cases of gallbladder cancer and 101 cases of gallstones was carried out. The dietary evaluation was carried out by the dietary recall method based on a preset questionnaire developed specifically for the present study, keeping in mind the common dietary habits prevailing in this part of the world. Odds ratios (OR) and 95% confidence interval (CI) were calculated for various dietary items. A significant reduction in odds ratio was seen with the consumption of radish (OR 0.4; 95% CI 0.17-0.94), green chilli (OR 0.45; 95% CI 0.21-0.94) and sweet potato (OR 0.33; 95% CI 0.13-0.83) among vegetables, and mango (OR 0.4; 95% CI 0.16-0.99), orange (OR; 0.45; 95% CI 0.22-0.93), melon (OR 0.3; 95% CI 0.14-0.64) and papaya (OR 0.44; 95% 0.2-0.64) among fruits. A reduction in odds was also seen with the consumption of cruciferous vegetables, beans, onion and turnip, however the difference was not statistically significant. On the other hand, an increase in the odds was observed with consumption of capsicum (OR 2.2), beef (OR 2.58), tea (OR 1.98), red chilli (OR 1.29) and mutton (OR 1.2), however the difference was statistically not significant. In conclusion, the results of the present study show a protective effect of vegetables and fruits on gallbladder carcinogenesis, but red meat (beef and mutton) was found to be associated with increased risk of gallbladder cancer.\",\n \"title\": \"Diet and gallbladder cancer: a case-control study.\"\n },\n {\n \"docid\": \"MED-2367\",\n \"text\": \"Naturally developing xenospecific Abs are well-documented barriers to xenograft transplantation in humans, but whether analogous xenoreactive T cell immunity develops is not known. We used an enzyme-linked immunospot assay to determine the frequency and cytokine profiles of xenoreactive PBLs from a panel of human volunteers. Because naive T cells produce only IL-2 in short term culture, IFN-gamma production by this approach is a measure of a memory immune response. Stimulation of human PBLs or purified T lymphocytes with stimulator cells from inbred swine revealed a high frequency of IFN-gamma producers with 5-fold fewer IL-2 producers. In contrast, lymphocytes obtained from neonatal umbilical cord blood contained swine-specific IL-2 producers but few IFN-gamma producers, which is what one would expect to find with a naive phenotype. Moreover, PBLs from adults with a history of abstention from pork consumption responded to swine cells with a significantly lower frequency of IFN-gamma producers than PBLs from adults with unrestricted diets did, suggesting that pork consumption may result in priming of swine-specific T cell immunity. Our findings provide the first evidence for naturally occurring xenospecific T cell immunity in humans. The detected strength of this memory response suggests that it will present a formidable barrier to transplantation of swine organs.\",\n \"title\": \"Naturally developing memory T cell xenoreactivity to swine antigens in human peripheral blood lymphocytes.\"\n },\n {\n \"docid\": \"MED-4299\",\n \"text\": \"The evolution of the human diet over the past 10,000 years from a Paleolithic diet to our current modern pattern of intake has resulted in profound changes in feeding behavior. Shifts have occurred from diets high in fruits, vegetables, lean meats, and seafood to processed foods high in sodium and hydrogenated fats and low in fiber. These dietary changes have adversely affected dietary parameters known to be related to health, resulting in an increase in obesity and chronic disease, including cardiovascular disease (CVD), diabetes, and cancer. Some intervention trials using Paleolithic dietary patterns have shown promising results with favorable changes in CVD and diabetes risk factors. However, such benefits may be offset by disadvantages of the Paleolithic diet, which is low in vitamin D and calcium and high in fish potentially containing environmental toxins. More advantageous would be promotion of foods and food ingredients from our ancestral era that have been shown to possess health benefits in the form of functional foods. Many studies have investigated the health benefits of various functional food ingredients, including omega-3 fatty acids, polyphenols, fiber, and plant sterols. These bioactive compounds may help to prevent and reduce incidence of chronic diseases, which in turn could lead to health cost savings ranging from $2 to $3 billion per year as estimated by case studies using omega-3 and plant sterols as examples. Thus, public health benefits should result from promotion of the positive components of Paleolithic diets as functional foods.\",\n \"title\": \"Evolution of the human diet: linking our ancestral diet to modern functional foods as a means of chronic disease prevention.\"\n },\n {\n \"docid\": \"MED-2451\",\n \"text\": \"BACKGROUND—A prospective cohort study of 2512 Welshmen aged 45-59 living in Caerphilly in 1979-1983 was used to investigate associations between diet and lung function. METHODS—At baseline (phase I) and at five year follow up (phase II), forced expiratory volume in one second (FEV1) was measured using a McDermott spirometer and dietary data were obtained using a semi-quantitative food frequency questionnaire. RESULTS—Good lung function, indicated by high maximum FEV1 given age and height, was associated with high intakes of vitamin C, vitamin E, β-carotene, citrus fruit, apples, and the frequent consumption of fruit juices/squashes. Lung function was inversely associated with magnesium intake but there was no evidence of an association with fatty fish. Following adjustment for confounders including body mass index, smoking history, social class, exercise, and total energy intake, only the associations with vitamin E and apples persisted, with lung function estimated to be 39 ml (95% confidence interval (CI) 9 to 69) higher for vitamin E intakes one standard deviation (SD) apart and 138 ml higher (95% CI 58to 218) for those eating five or more apples per week compared with non-consumers. Decline in lung function between phases was not significantly associated with the changing intakes of apples or vitamin E. An association between high average apple consumption and slow decline in lung function lost significance after adjustment for confounders. CONCLUSIONS—A strong positive association is seen between lung function and the number of apples eaten per week cross sectionally, consistent with a protective effect of hard fruit rather than soft/citrus fruit. The recent suggestion that such effects are reversible was not supported by our longitudinal analysis.\",\n \"title\": \"Diet, lung function, and lung function decline in a cohort of 2512 middle aged men\"\n },\n {\n \"docid\": \"MED-3320\",\n \"text\": \"OBJECTIVES: Reticuloendotheliosis viruses (REV) are a group of retroviruses like avian leukosis/sarcoma viruses (ALSV) that naturally infect and cause cancers in chickens. We recently found that ALSV antibody levels were associated with job tasks in the poultry industry. The objectives of this study are to examine whether a similar association can be found with REV antibody levels and to examine the correlation between REV and ALSV antibody levels. METHODS: Relative risk was estimated comparing REV antibody levels of 45 poultry workers with those of 44 controls. The expected mean antibody level was predicted for the association with employment by a generalized linear model. Correlation coefficient was measured between ALSV and REV antibody levels. RESULTS: REV antibody levels were significantly higher in poultry workers than in control subjects and were associated with gender and employment conditions, especially employment duration. The relative risk was significantly higher for some job categories. A significant correlation was observed between REV and ALSV antibody levels, which was strong among poultry workers, but weak among the control subjects. CONCLUSION: Antibody levels can be validly used to identify certain job tasks associated with high risk of exposure to REV in the workplace, and the practical implication is recommendations for protection at these job tasks. Importantly, in situations where there is exposure to multiple pathogens in the workplace, the analysis of antibody levels of one pathogen may sufficiently represent exposure to the other correlated pathogens. This suggested exposure assessment may hold true for pathogens with a similar route of transmission.\",\n \"title\": \"Industrial hygiene assessment of reticuloendotheliosis viruses exposure in the poultry industry.\"\n },\n {\n \"docid\": \"MED-4515\",\n \"text\": \"BACKGROUND: Low-carbohydrate, high-animal protein diets, which are advocated for weight loss, may not promote the desired reduction in low-density lipoprotein cholesterol (LDL-C) concentration. The effect of exchanging the animal proteins and fats for those of vegetable origin has not been tested. Our objective was to determine the effect on weight loss and LDL-C concentration of a low-carbohydrate diet high in vegetable proteins from gluten, soy, nuts, fruits, vegetables, cereals, and vegetable oils compared with a high-carbohydrate diet based on low-fat dairy and whole grain products. METHODS: A total of 47 overweight hyperlipidemic men and women consumed either (1) a low-carbohydrate (26% of total calories), high-vegetable protein (31% from gluten, soy, nuts, fruit, vegetables, and cereals), and vegetable oil (43%) plant-based diet or (2) a high-carbohydrate lacto-ovo vegetarian diet (58% carbohydrate, 16% protein, and 25% fat) for 4 weeks each in a parallel study design. The study food was provided at 60% of calorie requirements. RESULTS: Of the 47 subjects, 44 (94%) (test, n = 22 [92%]; control, n = 22 [96%]) completed the study. Weight loss was similar for both diets (approximately 4.0 kg). However, reductions in LDL-C concentration and total cholesterol-HDL-C and apolipoprotein B-apolipoprotein AI ratios were greater for the low-carbohydrate compared with the high-carbohydrate diet (-8.1% [P = .002], -8.7% [P = .004], and -9.6% [P = .001], respectively). Reductions in systolic and diastolic blood pressure were also seen (-1.9% [P = .052] and -2.4% [P = .02], respectively). CONCLUSION: A low-carbohydrate plant-based diet has lipid-lowering advantages over a high-carbohydrate, low-fat weight-loss diet in improving heart disease risk factors not seen with conventional low-fat diets with animal products.\",\n \"title\": \"The effect of a plant-based low-carbohydrate (\\\"Eco-Atkins\\\") diet on body weight and blood lipid concentrations in hyperlipidemic subjects.\"\n },\n {\n \"docid\": \"MED-3456\",\n \"text\": \"Pharmacological antioxidant vitamins have previously been investigated for a prophylactic effect against exercise-induced oxidative stress. However, large doses are often required and may lead to a state of pro-oxidation and oxidative damage. Watercress contains an array of nutritional compounds such as β-carotene and α-tocopherol which may increase protection against exercise-induced oxidative stress. The present randomised controlled investigation was designed to test the hypothesis that acute (consumption 2 h before exercise) and chronic (8 weeks consumption) watercress supplementation can attenuate exercise-induced oxidative stress. A total of ten apparently healthy male subjects (age 23 (SD 4) years, stature 179 (SD 10) cm and body mass 74 (SD 15) kg) were recruited to complete the 8-week chronic watercress intervention period (and then 8 weeks of control, with no ingestion) of the experiment before crossing over in order to compete the single-dose acute phase (with control, no ingestion). Blood samples were taken at baseline (pre-supplementation), at rest (pre-exercise) and following exercise. Each subject completed an incremental exercise test to volitional exhaustion following chronic and acute watercress supplementation or control. The main findings show an exercise-induced increase in DNA damage and lipid peroxidation over both acute and chronic control supplementation phases (P< 0.05 v. supplementation), while acute and chronic watercress attenuated DNA damage and lipid peroxidation and decreased H₂O₂ accumulation following exhaustive exercise (P< 0.05 v. control). A marked increase in the main lipid-soluble antioxidants (α-tocopherol, γ-tocopherol and xanthophyll) was observed following watercress supplementation (P< 0.05 v. control) in both experimental phases. These findings suggest that short- and long-term watercress ingestion has potential antioxidant effects against exercise-induced DNA damage and lipid peroxidation.\",\n \"title\": \"Acute and chronic watercress supplementation attenuates exercise-induced peripheral mononuclear cell DNA damage and lipid peroxidation.\"\n },\n {\n \"docid\": \"MED-2471\",\n \"text\": \"The International Study of Asthma and Allergies in Childhood (ISAAC) Phase One showed large worldwide variations in the prevalence of symptoms of asthma, rhinoconjunctivitis and eczema, up to 10 to 20 fold between countries. Ecological analyses were undertaken with ISAAC Phase One data to explore factors that may have contributed to these variations, and are summarised and reviewed here. In ISAAC Phase One the prevalence of symptoms in the past 12 months of asthma, rhinoconjunctivitis and eczema were estimated from studies in 463,801 children aged 13 - 14 years in 155 centres in 56 countries, and in 257,800 children aged 6-7 years in 91 centres in 38 countries. Ecological analyses were undertaken between symptom prevalence and the following: Gross National Product per capita (GNP), food intake, immunisation rates, tuberculosis notifications, climatic factors, tobacco consumption, pollen, antibiotic sales, paracetamol sales, and outdoor air pollution. Symptom prevalence of all three conditions was positively associated with GNP, trans fatty acids, paracetamol, and women smoking, and inversely associated with food of plant origin, pollen, immunisations, tuberculosis notifications, air pollution, and men smoking. The magnitude of these associations was small, but consistent in direction between conditions. There were mixed associations of climate and antibiotic sales with symptom prevalence. The potential causality of these associations warrant further investigation. Factors which prevent the development of these conditions, or where there is an absence of a positive correlation at a population level may be as important from the policy viewpoint as a focus on the positive risk factors. Interventions based on small associations may have the potential for a large public health benefit.\",\n \"title\": \"Which population level environmental factors are associated with asthma, rhinoconjunctivitis and eczema? Review of the ecological analyses of ISAAC Phase One\"\n },\n {\n \"docid\": \"MED-2484\",\n \"text\": \"Paediatric asthma is a major clinical concern worldwide and represents a huge burden on family and society. It accounts for a large number of lost school days and may deprive the child of both academic achievement and social interaction. Childhood asthma also places strain on healthcare resources as a result of doctor and hospital visits and the cost of treatment. The prevalence of asthma varies worldwide, possibly because of different exposure to respiratory infection, indoor and outdoor pollution, and diet. Certain risk factors appear to predispose children to developing asthma and atopic disease, including incidence and severity of wheezing, atopy, maternal smoking, and number of fever episodes. This paper discusses the burden, prevalence, and risk factors associated with paediatric asthma.\",\n \"title\": \"The burden of childhood asthma\"\n },\n {\n \"docid\": \"MED-3233\",\n \"text\": \"Our objective in this study was to determine the effects of a high-protein and high-potential renal acid load (PRAL) diet on calcium (Ca) absorption and retention and markers of bone metabolism. In a randomized crossover design, 16 postmenopausal women consumed 2 diets: 1 with low protein and low PRAL (LPLP; total protein: 61 g/d; PRAL: -48 mEq/d) and 1 with high protein and high PRAL (HPHP; total protein: 118 g/d; PRAL: 33 mEq/d) for 7 wk each separated by a 1-wk break. Ca absorption was measured by whole body scintillation counting of radio-labeled (47)Ca. Compared with the LPLP diet, the HPHP diet increased participants' serum IGF-I concentrations (P < 0.0001), decreased serum intact PTH concentrations (P < 0.001), and increased fractional (47)Ca absorption (mean ± pooled SD: 22.3 vs. 26.5 ± 5.4%; P < 0.05) and urinary Ca excretion (156 vs. 203 ± 63 mg/d; P = 0.005). The net difference between the amount of Ca absorbed and excreted in urine did not differ between 2 diet periods (55 vs. 28 ± 51 mg/d). The dietary treatments did not affect other markers of bone metabolism. In summary, a diet high in protein and PRAL increases the fractional absorption of dietary Ca, which partially compensates for increased urinary Ca, in postmenopausal women. The increased IGF-I and decreased PTH concentrations in serum, with no change in biomarkers of bone resorption or formation, indicate a high-protein diet has no adverse effects on bone health.\",\n \"title\": \"A diet high in meat protein and potential renal acid load increases fractional calcium absorption and urinary calcium excretion without affecting m...\"\n },\n {\n \"docid\": \"MED-3373\",\n \"text\": \"Objectives. We considered the relationship between an urban adult population's fruit and vegetable consumption and several selected social and psychological processes, beneficial aesthetic experiences, and garden participation. Methods. We conducted a population-based survey representing 436 residents across 58 block groups in Denver, Colorado, from 2006 to 2007. We used multilevel statistical models to evaluate the survey data. Results. Neighborhood aesthetics, social involvement, and community garden participation were significantly associated with fruit and vegetable intake. Community gardeners consumed fruits and vegetables 5.7 times per day, compared with home gardeners (4.6 times per day) and nongardeners (3.9 times per day). Moreover, 56% of community gardeners met national recommendations to consume fruits and vegetables at least 5 times per day, compared with 37% of home gardeners and 25% of nongardeners. Conclusions. Our study results shed light on neighborhood processes that affect food-related behaviors and provides insights about the potential of community gardens to affect these behaviors. The qualities intrinsic to community gardens make them a unique intervention that can narrow the divide between people and the places where food is grown and increase local opportunities to eat better.\",\n \"title\": \"The Influence of Social Involvement, Neighborhood Aesthetics, and Community Garden Participation on Fruit and Vegetable Consumption\"\n },\n {\n \"docid\": \"MED-3453\",\n \"text\": \"There has been no investigation to determine if the widely used over-the-counter, water-soluble antioxidants vitamin C and N-acetyl-cysteine (NAC) could act as pro-oxidants in humans during inflammatory conditions. We induced an acute-phase inflammatory response by an eccentric arm muscle injury. The inflammation was characterized by edema, swelling, pain, and increases in plasma inflammatory indicators, myeloperoxidase and interleukin-6. Immediately following the injury, subjects consumed a placebo or vitamin C (12.5 mg/kg body weight) and NAC (10 mg/kg body weight) for 7 d. The resulting muscle injury caused increased levels of serum bleomycin-detectable iron and the amount of iron was higher in the vitamin C and NAC group. The concentrations of lactate dehydrogenase (LDH), creatine kinase (CK), and myoglobin were significantly elevated 2, 3, and 4 d postinjury and returned to baseline levels by day 7. In addition, LDH and CK activities were elevated to a greater extent in the vitamin C and NAC group. Levels of markers for oxidative stress (lipid hydroperoxides and 8-iso prostaglandin F2alpha; 8-Iso-PGF2alpha) and antioxidant enzyme activities were also elevated post-injury. The subjects receiving vitamin C and NAC had higher levels of lipid hydroperoxides and 8-Iso-PGF2alpha 2 d after the exercise. This acute human inflammatory model strongly suggests that vitamin C and NAC supplementation immediately post-injury, transiently increases tissue damage and oxidative stress.\",\n \"title\": \"Supplementation with vitamin C and N-acetyl-cysteine increases oxidative stress in humans after an acute muscle injury induced by eccentric exercise.\"\n },\n {\n \"docid\": \"MED-3789\",\n \"text\": \"Background: Meat, milk, and eggs have been inconsistently associated with the risk of advanced prostate cancer. These foods are sources of choline—a nutrient that may affect prostate cancer progression through cell membrane function and one-carbon metabolism. No study has examined dietary choline and the risk of lethal prostate cancer. Objective: Our objective was to examine whether dietary choline, choline-containing compounds, and betaine (a choline metabolite) increase the risk of lethal prostate cancer. Design: We prospectively examined the intake of these nutrients and the risk of lethal prostate cancer among 47,896 men in the Health Professionals Follow-Up Study. In a case-only survival analysis, we examined the postdiagnostic intake of these nutrients and the risk of lethal prostate cancer among 4282 men with an initial diagnosis of nonmetastatic disease during follow-up. Diet was assessed with a validated questionnaire 6 times during 22 y of follow-up. Results: In the incidence analysis, we observed 695 lethal prostate cancers during 879,627 person-years. Men in the highest quintile of choline intake had a 70% increased risk of lethal prostate cancer (HR: 1.70; 95% CI: 1.18, 2.45; P-trend = 0.005). In the case-only survival analysis, we observed 271 lethal cases during 33,679 person-years. Postdiagnostic choline intake was not statistically significantly associated with the risk of lethal prostate cancer (HR for quintile 5 compared with quintile 1: 1.69; 95% CI: 0.93, 3.09; P-trend = 0.20). Conclusion: Of the 47,896 men in our study population, choline intake was associated with an increased risk of lethal prostate cancer.\",\n \"title\": \"Choline intake and risk of lethal prostate cancer: incidence and survival\"\n },\n {\n \"docid\": \"MED-2205\",\n \"text\": \"AIM: To investigate the effects of proteins purified from sweet potato storage roots on human colorectal cancer cell lines. METHODS: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Hoechst 33258 nuclear staining and Boyden transwell chamber methods were used to determine whether purified sweet potato protein (SPP) from fresh sweet potato roots affected proliferation, migration and invasion, respectively, of human colorectal cancer SW480 cells in vitro. The inhibitory effects of SPP on growth of human colorectal cancer HCT-8 cells intraperitoneally xenografted in nude mice and spontaneous lung metastasis of murine Lewis lung carcinoma 3LL cells subcutaneously transplanted in C57 BL/6 mice were also investigated in vivo. RESULTS: SPP inhibited the proliferation of SW480 cells in a dose-dependent manner, with an IC50 value of 38.732 μmol/L (r2 = 0.980, P = 0.003) in the MTT assay. Hoechst 33258 nuclear staining further revealed inhibition of cell viability and induction of apoptosis by SPP. The transwell assay disclosed significant reduction in migrated cells/field by 8 μmol/L SPP (8.4 ± 2.6 vs 23.3 ± 5.4, P = 0.031) and invaded cells/field through the ECMatrix by 0.8 μmol/L SPP, compared with the control (25.2 ± 5.2 vs 34.8 ± 6.1, P = 0.038). Both intraperitoneal (ip) and intragastric (ig) administration of SPP led to significant suppression of growth of intraperitoneally inoculated HCT-8 cells in nude mice to 58.0% ± 5.9% (P = 0.037) and 43.5% ± 7.1% (P = 0.004) of the controls, respectively, after 9 d treatment. Bloody ascites additionally disappeared after ip injection of trypsin inhibitor. Notably, ig and ip administration of SPP induced a significant decrease in spontaneous pulmonary metastatic nodule formation in C57 BL/6 mice (21.0 ± 12.3 and 27.3 ± 12.7 nodules/lung vs 42.5 ± 4.5 nodules/lung in controls, respectively, P < 0.05) after 25 d treatment. Moreover, the average weight of primary tumor nodules in the hind leg of mice decreased from 8.2 ± 1.3 g/mice in the control to 6.1 ± 1.4 g/mice in the ip group (P = 0.035). CONCLUSION: SPP exerts significant antiproliferative and antimetastatic effects on human colorectal cancer cell lines, both in vitro and in vivo.\",\n \"title\": \"Anticancer effects of sweet potato protein on human colorectal cancer cells\"\n },\n {\n \"docid\": \"MED-3294\",\n \"text\": \"In the past two decades or so, a number of viruses have emerged in the global swine population. Some, such as porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2), cause economically important diseases in pigs, whereas others such as porcine torque teno virus (TTV), now known as Torque teno sus virus (TTSuV), porcine bocavirus (PBoV) and related novel parvoviruses, porcine kobuvirus, porcine toroviruses (PToV) and porcine lymphotropic herpesviruses (PLHV), are mostly subclinical in swine herds. Although some emerging swine viruses such as swine hepatitis E virus (swine HEV), porcine endogenous retrovirus (PERV) and porcine sapovirus (porcine SaV) may have a limited clinical implication in swine health, they do pose a potential public health concern in humans due to zoonotic (swine HEV) or potential zoonotic (porcine SaV) and xenozoonotic (PERV, PLHV) risks. Other emerging viruses such as Nipah virus, Bungowannah virus and Menangle virus not only cause diseases in pigs but some also pose important zoonotic threat to humans. This article focuses on emerging and re-emerging swine viruses that have a limited or uncertain clinical and economic impact on pig health. The transmission, epidemiology and pathogenic potential of these viruses are discussed. In addition, the two economically important emerging viruses, PRRSV and PCV2, are also briefly discussed to identify important knowledge gaps. © 2012 Blackwell Verlag GmbH.\",\n \"title\": \"Emerging and re-emerging swine viruses.\"\n },\n {\n \"docid\": \"MED-1257\",\n \"text\": \"Meat protein is associated with an increase in risk of heart disease. Recent data have shown that meat protein appeared to be associated with weight gain over 6.5 years, with 1 kg of weight increase per 125 g of meat per day. In the Nurses' Health Study, diets low in red meat, containing nuts, low-fat dairy, poultry, or fish, were associated with a 13% to 30% lower risk of CHD compared with diets high in meat. Low-carbohydrate diets high in animal protein were associated with a 23% higher total mortality rate whereas low-carbohydrate diets high in vegetable protein were associated with a 20% lower total mortality rate. Recent soy interventions have been assessed by the American Heart Association and found to be associated with only small reductions in LDL cholesterol. Although dairy intake has been associated with a lower weight and lower insulin resistance and metabolic syndrome, the only long-term (6 months) dairy intervention performed so far has shown no effects on these parameters.\",\n \"title\": \"Protein and coronary heart disease: the role of different protein sources.\"\n },\n {\n \"docid\": \"MED-2364\",\n \"text\": \"We have recently demonstrated that both antibodies to Gal alpha(1,3)Gal, and the Gal alpha(1,3)Gal binding lectin (IB4), bind a synthetic peptide (DAHWESWL), there being a similar recognition of carbohydrate and peptide structures. We now report that the anti-Gal alpha(1,3)Gal antibodies and IB4 lectin also react with peptides encoded by mucin genes (MUC 1, 3, 4)-sequences known to be rich in serine, threonine and proline. This activity was demonstrated (1) by the ability of mucin derived peptides to block the reaction of anti-Gal alpha(1,3)Gal antibodies and IB4 lectin with a Gal alpha(1,3)Gal+ pig endothelial cell line; the reactions were specific and did not occur with a random peptide containing the same sequences or with other mucin peptides; (2) by the fact that anti-mucin1 antibodies could react with the Gal alpha(1,3)Gal expressed after transfection of COS cells (Gal alpha(1,3)Gal-,Muc1-) with cDNA encoding the pig alpha, 3galactosyltransferase; and (3) that the IB4 lectin and anti-Gal alpha(1,3)Gal antibodies could react with mucin 1 found on the surface of human breast cancer cells. Thus natural occurring anti-Gal alpha(1,3)Gal antibodies found in all human serum can react with self (Muc1) peptides expressed in large amounts on the surface of tumour cells but not on normal cells. The findings are of interest and serve to explain the previously reported findings that human cells can, at times, express Gal alpha(1,3)Gal; such expression is an artefact, the reaction is due to the phenomenon described herein, i.e. that anti-Gal alpha(1,3)Gal antibodies react with mucin peptides.\",\n \"title\": \"Natural human anti-Gal alpha(1,3)Gal antibodies react with human mucin peptides.\"\n },\n {\n \"docid\": \"MED-3353\",\n \"text\": \"Skin blood perfusion and oxygenation depends upon cardiovascular, hormonal and circulatory health in humans and provides socio-sexual signals of underlying physiology, dominance and reproductive status in some primates. We allowed participants to manipulate colour calibrated facial photographs along empirically-measured oxygenated and deoxygenated blood colour axes both separately and simultaneously, to optimise healthy appearance. Participants increased skin blood colour, particularly oxygenated, above basal levels to optimise healthy appearance. We show, therefore, that skin blood perfusion and oxygenation influence perceived health in a way that may be important to mate choice.\",\n \"title\": \"Skin Blood Perfusion and Oxygenation Colour Affect Perceived Human Health\"\n },\n {\n \"docid\": \"MED-3371\",\n \"text\": \"Background: The overconsumption of energy-dense foods leads to excessive energy intakes. The substitution of low-energy-dense vegetables for foods higher in energy density can help decrease energy intakes but may be difficult to implement if individuals dislike the taste of vegetables. Objective: We investigated whether incorporating puréed vegetables to decrease the energy density of entrées at multiple meals reduced daily energy intakes and increased daily vegetable intakes. Design: In this crossover study, 20 men and 21 women ate ad libitum breakfast, lunch, and dinner in the laboratory once a week for 3 wk. Across conditions, entrées at meals varied in energy density from standard versions (100% condition) to reduced versions (85% and 75% conditions) by the covert incorporation of 3 or 4.5 times the amount of puréed vegetables. Entrées were accompanied by unmanipulated side dishes. Participants rated their hunger and fullness before and after meals. Results: Subjects consumed a consistent weight of foods across conditions of energy density; thus, the daily energy intake significantly decreased by 202 ± 60 kcal in the 85% condition (P < 0.001) and by 357 ± 47 kcal in the 75% condition (P < 0.0001). Daily vegetable consumption significantly increased from 270 ± 17 g of vegetables in the 100% condition to 487 ± 25 g of vegetables in the 75% condition (P < 0.0001). Despite the decreased energy intake, ratings of hunger and fullness did not significantly differ across conditions. Entrées were rated as similar in palatability across conditions. Conclusions: Large amounts of puréed vegetables can be incorporated into various foods to decrease the energy density. This strategy can lead to substantial reductions in energy intakes and increases in vegetable intakes. This trial was registered at clinicaltrials.gov as NCT01165086.\",\n \"title\": \"Hidden vegetables: an effective strategy to reduce energy intake and increase vegetable intake in adults\"\n },\n {\n \"docid\": \"MED-3243\",\n \"text\": \"OBJECTIVES: Considerable evidence has shown that diet can affect both the incidence and the progression of prostate cancer. The objective of this study was to determine whether men in this situation could make a change to a diet emphasizing plant-based foods and fish and to examine the effect on quality of life (QOL) and prostate-specific antigen (PSA) velocity. METHODS: A total of 36 men and their partners were randomly assigned to attend a series of 11 dietary and cooking classes that also integrated mindfulness practice as a support in making the change or a wait-list control group. Assessments were made of dietary intake, QOL, and PSA at baseline, after intervention (11 weeks), and 3 months after intervention. RESULTS: The intervention group showed significant reductions in the consumption of saturated fat and increased consumption of vegetable proteins with accompanying reductions in animal proteins, including dairy products. They also showed increased QOL. Although no significant change was found in the rate of PSA increase between the two groups, the mean PSA doubling time for the intervention group was substantially longer at the 3-month follow-up visit than that of the controls. CONCLUSIONS: Men with a increasing PSA level after primary treatment were able to make a change to a prostate-healthy diet, accompanied by increases in QOL. No significant difference was found in the log PSA slope between the two groups; however, the PSA doubling time increased substantially in the intervention group compared with that in the controls. Future trials should examine the effect of the prostate-healthy diet with a larger sample of men for a longer period.\",\n \"title\": \"A dietary intervention for recurrent prostate cancer after definitive primary treatment: results of a randomized pilot trial.\"\n },\n {\n \"docid\": \"MED-3317\",\n \"text\": \"Twenty-four patients, all of whom were exposed to aerosolized porcine brain tissue through work-place environment (abattoir), developed a syndrome of immune-mediated polyradiculoneuropathy; three also had central nervous system manifestations (transverse myelitis, meningoencephalitis, and aseptic meningitis). Patients had characteristic electrophysiological findings of very distal and proximal conduction slowing (prolonged distal and F-wave latencies, regions where the blood-nerve barrier is the most permeable) and all patients' serum contained a novel IgG immunofluorescence pattern. Nerve pathology, when available, showed mild changes of segmental demyelination, axonal degeneration, and inflammatory changes. Patients had meaningful improvement of symptoms and electrophysiologic findings with immune therapy and with removal of exposure to aerosolized brain tissue. We postulate that this outbreak is an auto-immune polyradiculoneuropathy triggered by occupational exposure to multiple aerosolized porcine neural tissue antigens that result in neural damage where the blood-nerve barrier is the least robust. © 2011 Peripheral Nerve Society.\",\n \"title\": \"Auto-immune polyradiculoneuropathy and a novel IgG biomarker in workers exposed to aerosolized porcine brain.\"\n },\n {\n \"docid\": \"MED-2292\",\n \"text\": \"In industrialized nations, diverticular disease affects up to 70% of individuals by 60 years of age, with symptoms that can range from mild gastrointestinal disturbance to incapacitating pain. Diverticular disease appears to be related to increasing affluence and changed diet: Current theory holds that diverticular disease's origin is low-fiber diet. This explains why its incidence is highest and accelerating in the more prosperous countries where intake of fiber has decreased and intake of milled grains and refined sugars has increased over time. Not all patients develop symptoms, but if they do, the most frequent complaints associated with diverticulosis are cramping in the left-lower quadrant, bloating, constipation, and soiling. If diverticula perforate the gut's wall into the pericolic tissue, small and large abscesses, accompanied by bleeding, can form. Fistulization, when it occurs, most often penetrates to the bladder. Treatment addresses symptoms and may require hospitalization. During symptomatic periods, patients do best on low-fiber, bland diets. Once the acute episode or highly symptomatic period resolves or chronic disease is managed, patients should gradually increase dietary fiber to 20 to 30 grams daily or take dietary fiber in the form of bulk stimulants like psyllium.\",\n \"title\": \"Diverticular disease: eat your fiber!\"\n },\n {\n \"docid\": \"MED-2354\",\n \"text\": \"A new natural anti-alpha-galactosyl IgG antibody (anti-Gal) was found to be present in high titer in the serum of every normal individual studied. The antibody was isolated by affinity chromatography on a melibiose-Sepharose column. The reactivity of the antibody was assessed by its interaction with alpha-galactosyl residues on rabbit erythrocytes (RabRBC). The specificity was determined by inhibition experiments with various carbohydrates. The anti-Gal interacts with alpha-galactosyl residues, possibly on glycolipids of human RBC (HuRBC), after removal of membrane proteins by treatment with pronase. In addition, the anti-Gal bind specifically to normal and pathologically senescent HuRBC, suggesting a physiological role for this natural antibody in the aging of RBC. The ubiquitous presence of anti-Gal in high titers throughout life implies a constant antigenic stimulation. In addition to the theoretical interest in the antibody, the study of the anti-Gal reactivity seems to bear immunodiagnostic significance. Decrease in the antibody titer was found to reflect humoral immunodeficiency disorders.\",\n \"title\": \"A unique natural human IgG antibody with anti-alpha-galactosyl specificity\"\n },\n {\n \"docid\": \"MED-3687\",\n \"text\": \"This study was aimed at determining the probiotic potential of a large number of autochthonous lactic acid bacteria isolated from fruit and vegetables. Survival under simulated gastric and intestinal conditions showed that 35% of the strains, mainly belonging to the species Lactobacillus plantarum maintained high cell densities. Selected strains did not affect the immune-mediation by Caco-2 cells. All strains stimulated all 27 immune-mediators by peripheral blood mononuclear cells (PBMC). A significant (P<0.05; P<0.01) increase of the major part of cytokines and growth factors was found. A few chemokines were stimulated. Immune-mediators with pro-inflammatory activity (IL-17, EOTAXIN and IFNγ) were significantly (P<0.01) stimulated by all strains, followed by IL-1b>IP-10>IL-6>MIP1α. Stimulation of IL-12, IL-2 and IL-7 was strain dependent. Only a few strains increased the synthesis of cytokines with anti-inflammatory activity. Six L. plantarum strains were further selected. Four were defined as the strongly adhesive strains (more than 40 bacteria adhering to one Caco-2 cell), and 2 as the adhesive strains (5-40 bacteria adhering to one Caco-2 cell). Five strains grew and acidified chemically defined medium with fructo-oligosaccharides (FOS) as the only carbon source. End-products of FOS fermentation were found. All strains inhibited enterohemorragic Escherichia coli K12 and Bacillus megaterium F6 isolated from human sources. The results of this study showed that some autochthonous lactic acid bacteria from raw fruit and vegetables have functional features to be considered as novel probiotic candidates. Copyright © 2012 Elsevier Ltd. All rights reserved.\",\n \"title\": \"Novel probiotic candidates for humans isolated from raw fruits and vegetables.\"\n },\n {\n \"docid\": \"MED-2203\",\n \"text\": \"Constipation is a common health problem that adversely affects quality of life and the prognosis of hospitalized patients with acute coronary syndromes (ACS). The purpose of this study was to develop and test the sweet potato/footbath/acupressure massage (SFA) intervention as a safe treatment for prevention of constipation and to increase satisfaction with bowel emptying in hospitalized patients with ACS. The study was a prospective, randomized controlled trial with a sample of 93 patients (SFA group, n = 44; usual care group, n = 49). Patients in the SFA group received SFA intervention combined with usual care. The results showed that there were statistical differences between the two groups in terms of (1) the incidence of constipation; (2) the use of laxatives and enemas; (3) patients' subjective satisfaction with their bowel emptying during hospitalization; and (4) sensation of incomplete evacuation and anorectal obstruction/blockade. The SFA intervention was more effective, economical, and practical than usual care alone in managing constipation and satisfaction with defecation in patients hospitalized with ACS.\",\n \"title\": \"The effect of a sweet potato, footbath, and acupressure intervention in preventing constipation in hospitalized patients with acute coronary syndro...\"\n },\n {\n \"docid\": \"MED-2498\",\n \"text\": \"Dietary restriction (DR) and reduced growth factor signaling both elevate resistance to oxidative stress, reduce macromolecular damage, and increase lifespan in model organisms. In rodents, both DR and decreased growth factor signaling reduce the incidence of tumors and slow down cognitive decline and aging. DR reduces cancer and cardiovascular disease and mortality in monkeys, and reduces metabolic traits associated with diabetes, cardiovascular disease and cancer in humans. Neoplasias and diabetes are also rare in humans with loss of function mutations in the growth hormone receptor. DR and reduced growth factor signaling may thus slow aging by similar, evolutionarily conserved, mechanisms. We review these conserved anti-aging pathways in model organisms, discuss their link to disease prevention in mammals, and consider the negative side effects that might hinder interventions intended to extend healthy lifespan in humans.\",\n \"title\": \"Dietary Restriction, Growth Factors and Aging: from yeast to humans\"\n },\n {\n \"docid\": \"MED-3351\",\n \"text\": \"Based on evidence that the color red elicits avoidance motivation across contexts (Mehta & Zhu, 2009), two studies investigated the effect of the color red on snack food and soft drink consumption. In line with our hypothesis, participants drank less from a red labeled cup than from a blue labeled cup (Study 1), and ate less snack food from a red plate than from a blue or white plate (Study 2). The results suggest that red functions as a subtle stop signal that works outside of focused awareness and thereby reduces incidental food and drink intake. Copyright © 2012 Elsevier Ltd. All rights reserved.\",\n \"title\": \"The color red reduces snack food and soft drink intake.\"\n },\n {\n \"docid\": \"MED-5239\",\n \"text\": \"Epidemiological evidence points to increased dairy and meat consumption, staples of the Western diet, as major risk factors for the development of type 2 diabetes (T2D). This paper presents a new concept and comprehensive review of leucine-mediated cell signaling explaining the pathogenesis of T2D and obesity by leucine-induced over-stimulation of mammalian target of rapamycin complex 1 (mTORC1). mTORC1, a pivotal nutrient-sensitive kinase, promotes growth and cell proliferation in response to glucose, energy, growth factors and amino acids. Dairy proteins and meat stimulate insulin/insulin-like growth factor 1 signaling and provide high amounts of leucine, a primary and independent stimulator for mTORC1 activation. The downstream target of mTORC1, the kinase S6K1, induces insulin resistance by phosphorylation of insulin receptor substrate-1, thereby increasing the metabolic burden of β-cells. Moreover, leucine-mediated mTORC1-S6K1-signaling plays an important role in adipogenesis, thus increasing the risk of obesity-mediated insulin resistance. High consumption of leucine-rich proteins explains exaggerated mTORC1-dependent insulin secretion, increased β-cell growth and β-cell proliferation promoting an early onset of replicative β-cell senescence with subsequent β-cell apoptosis. Disturbances of β-cell mass regulation with increased β-cell proliferation and apoptosis as well as insulin resistance are hallmarks of T2D, which are all associated with hyperactivation of mTORC1. In contrast, the anti-diabetic drug metformin antagonizes leucine-mediated mTORC1 signaling. Plant-derived polyphenols and flavonoids are identified as natural inhibitors of mTORC1 and exert anti-diabetic and anti-obesity effects. Furthermore, bariatric surgery in obesity reduces increased plasma levels of leucine and other branched-chain amino acids. Attenuation of leucine-mediated mTORC1 signaling by defining appropriate upper limits of the daily intake of leucine-rich animal and dairy proteins may offer a great chance for the prevention of T2D and obesity, as well as other epidemic diseases of civilization with increased mTORC1 signaling, especially cancer and neurodegenerative diseases, which are frequently associated with T2D.\",\n \"title\": \"Leucine signaling in the pathogenesis of type 2 diabetes and obesity\"\n },\n {\n \"docid\": \"MED-3925\",\n \"text\": \"This study describes how foods rich in fisetin and hexacosanol added to a strict diet reversed most symptoms of Parkinson's disease (PD) in one patient. This is a case report involving outpatient care. The subject was a dietitian diagnosed with idiopathic PD in 2000 at the age of 53 years old, with a history of exposure to neurotoxins and no family history of PD. A basic diet started in 2000 consisted of predominantly fruits, vegetables, 100% whole grains, extra virgin olive oil, nuts, seeds, nonfat milk products, tea, coffee, spices, small amounts of dark chocolate, and less than 25 g of animal fat daily. The basic diet alone failed to prevent decline due to PD. In 2009, the basic diet was enhanced with a good dietary source of both fisetin and hexacosanol. Six months after the patient started the enhanced diet rich in fisetin and hexacosanol, a clinically significant improvement in symptoms was noted; the patient's attending neurologist reported that the clinical presentation of cogwheel rigidity, micrographia, bradykinesia, dystonia, constricted arm swing with gait, hypomimia, and retropulsion appeared to be resolved. The only worsening of symptoms occurred when the diet was not followed precisely. Little improvement in tremor or seborrhea was observed. The clinical improvement has persisted to date. To the best of our knowledge, this is the first case where adjunctive diet therapy resulted in a significant reduction of symptoms of PD without changing the type or increasing the amount of medications.\",\n \"title\": \"A diet low in animal fat and rich in N-hexacosanol and fisetin is effective in reducing symptoms of Parkinson's disease.\"\n },\n {\n \"docid\": \"MED-3773\",\n \"text\": \"The present study assessed the effects of mild dehydration on cognitive performance and mood of young males. A total of twenty-six men (age 20·0 (sd 0·3) years) participated in three randomised, single-blind, repeated-measures trials: exercise-induced dehydration plus a diuretic (DD; 40 mg furosemide); exercise-induced dehydration plus placebo containing no diuretic (DN); exercise while maintaining euhydration plus placebo (EU; control condition). Each trial included three 40 min treadmill walks at 5·6 km/h, 5 % grade in a 27·7°C environment. A comprehensive computerised six-task cognitive test battery, the profile of mood states questionnaire and the symptom questionnaire (headache, concentration and task difficulty) were administered during each trial. Paired t tests compared the DD and DN trials resulting in >1 % body mass loss (mean 1·59 (sd 0·42) %) with the volunteer's EU trial (0·01 (sd 0·03) %). Dehydration degraded specific aspects of cognitive performance: errors increased on visual vigilance (P = 0·048) and visual working memory response latency slowed (P = 0·021). Fatigue and tension/anxiety increased due to dehydration at rest (P = 0·040 and 0·029) and fatigue during exercise (P = 0·026). Plasma osmolality increased due to dehydration (P < 0·001) but resting gastrointestinal temperature was not altered (P = 0·238). In conclusion, mild dehydration without hyperthermia in men induced adverse changes in vigilance and working memory, and increased tension/anxiety and fatigue.\",\n \"title\": \"Mild dehydration impairs cognitive performance and mood of men.\"\n },\n {\n \"docid\": \"MED-3354\",\n \"text\": \"The luminance contrast between facial features and facial skin is greater in women than in men, and women's use of make-up enhances this contrast. In black-and-white photographs, increased luminance contrast enhances femininity and attractiveness in women's faces, but reduces masculinity and attractiveness in men's faces. In Caucasians, much of the contrast between the lips and facial skin is in redness. Red lips have been considered attractive in women in geographically and temporally diverse cultures, possibly because they mimic vasodilation associated with sexual arousal. Here, we investigate the effects of lip luminance and colour contrast on the attractiveness and sex typicality (masculinity/femininity) of human faces. In a Caucasian sample, we allowed participants to manipulate the colour of the lips in colour-calibrated face photographs along CIELab L* (light--dark), a* (red--green), and b* (yellow--blue) axes to enhance apparent attractiveness and sex typicality. Participants increased redness contrast to enhance femininity and attractiveness of female faces, but reduced redness contrast to enhance masculinity of men's faces. Lip blueness was reduced more in female than male faces. Increased lightness contrast enhanced the attractiveness of both sexes, and had little effect on perceptions of sex typicality. The association between lip colour contrast and attractiveness in women's faces may be attributable to its association with oxygenated blood perfusion indicating oestrogen levels, sexual arousal, and cardiac and respiratory health.\",\n \"title\": \"Lip colour affects perceived sex typicality and attractiveness of human faces.\"\n },\n {\n \"docid\": \"MED-5197\",\n \"text\": \"BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) and heterocyclic amines (HCAs) are carcinogens formed in or on the surface of well-done meat, cooked at high temperature. METHODS: We estimated breast cancer risk in relation to intake of cooked meat in a population-based, case-control study (1508 cases and 1556 controls) conducted in Long Island, NY from 1996 to 1997. Lifetime intakes of grilled or barbecued and smoked meats were derived from the interviewer-administered questionnaire data. Dietary intakes of PAH and HCA were derived from the self-administered modified Block food frequency questionnaire of intake 1 year before reference date. Unconditional logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Modest increased risk was observed among postmenopausal, but not premenopausal, women consuming the most grilled or barbecued and smoked meats over the life course (OR = 1.47; CI = 1.12-1.92 for highest vs. lowest tertile of intake). Postmenopausal women with low fruit and vegetable intake, but high lifetime intake of grilled or barbecued and smoked meats, had a higher OR of 1.74 (CI = 1.20-2.50). No associations were observed with the food frequency questionnaire-derived intake measures of PAHs and HCAs, with the possible exception of benzo(alpha)pyrene from meat among postmenopausal women whose tumors were positive for both estrogen receptors and progesterone receptors (OR = 1.47; CI = 0.99-2.19). CONCLUSIONS: These results support the accumulating evidence that consumption of meats cooked by methods that promote carcinogen formation may increase risk of postmenopausal breast cancer.\",\n \"title\": \"Cooked meat and risk of breast cancer--lifetime versus recent dietary intake.\"\n },\n {\n \"docid\": \"MED-3933\",\n \"text\": \"In this study, the effects of a diet rich in insoluble fiber (DRIF) on motor disability and the peripheral pharmacokinetics of orally administered L-dopa in Parkinsonian patients with marked constipation are analyzed. We found a useful effect of a DRIF on plasma L-dopa concentration and motor function. The greatest effect on the plasma L-dopa levels was found early (at 30 and 60 min) after oral administration. There was a relationship between the improvement of constipation and the higher bioavailability of L-dopa. DRIF can be a coadjuvant treatment in patients with Parkinson's disease.\",\n \"title\": \"Clinical and pharmacokinetic effects of a diet rich in insoluble fiber on Parkinson disease.\"\n },\n {\n \"docid\": \"MED-2831\",\n \"text\": \"TNFs are major mediators of inflammation and inflammation-related diseases, hence, the United States Food and Drug Administration (FDA) has approved the use of blockers of the cytokine, TNF-α, for the treatment of osteoarthritis, inflammatory bowel disease, psoriasis and ankylosis. These drugs include the chimeric TNF antibody (infliximab), humanized TNF-α antibody (Humira) and soluble TNF receptor-II (Enbrel) and are associated with a total cumulative market value of more than $20 billion a year. As well as being expensive ($15 000–20 000 per person per year), these drugs have to be injected and have enough adverse effects to be given a black label warning by the FDA. In the current report, we describe an alternative, curcumin (diferuloylmethane), a component of turmeric (Curcuma longa) that is very inexpensive, orally bioavailable and highly safe in humans, yet can block TNF-α action and production in in vitro models, in animal models and in humans. In addition, we provide evidence for curcumin's activities against all of the diseases for which TNF blockers are currently being used. Mechanisms by which curcumin inhibits the production and the cell signalling pathways activated by this cytokine are also discussed. With health-care costs and safety being major issues today, this golden spice may help provide the solution. Linked Articles This article is part of a themed section on Emerging Therapeutic Aspects in Oncology. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.169.issue-8\",\n \"title\": \"Curcumin: an orally bioavailable blocker of TNF and other pro-inflammatory biomarkers\"\n },\n {\n \"docid\": \"MED-2448\",\n \"text\": \"A double-blind comparative study was conducted on cedar pollinosis patients in order to evaluate the treatment efficacy of apple polyphenol (Ap). Ap was administered (500 mg) once daily for 12 weeks, starting about 2 weeks prior to cedar pollen dispersion. Pollinosis symptoms during the study were evaluated according to the classification in the guidelines for allergic rhinitis diagnosis and treatment. The results show that the sneezing score was significantly lower for the Ap group than with the placebo group during the early period of pollen dispersion and during the main dispersion period. In addition, no adverse reactions were induced by Ap during the study. These results suggest that Ap may alleviate the symptoms of cedar pollinosis.\",\n \"title\": \"Clinical efficacy of apple polyphenol for treating cedar pollinosis.\"\n },\n {\n \"docid\": \"MED-2365\",\n \"text\": \"Twenty-five patients living in a tick-endemic region of Sydney, New South Wales developed red meat allergy after experiencing large local reactions to tick bites. This represents a potentially novel cross-reaction between an arthropod and a food protein. (MJA 2009; 190: 510-511).\",\n \"title\": \"An association between tick bite reactions and red meat allergy in humans.\"\n },\n {\n \"docid\": \"MED-3307\",\n \"text\": \"OBJECTIVE: workers in slaughterhouses and processing plants that handle pigs, and pork butchers/meatcutters have been little studied for health risks associated with employment, in spite of the fact that they are potentially exposed to oncogenic and non-oncogenic transmissible agents and chemical carcinogens at work. We report here on an update of mortality in 510 workers employed in abattoirs and processing plants that almost exclusively handled pigs and pork products. METHODS: standardized mortality ratios (SMRs) were estimated for the cohort as a whole, and in subgroups defined by race and sex, using the corresponding US general population mortality rates for comparison. Study subjects were followed up from January 1950 to December 2006, during which time 45% of them died. RESULTS: mortality was significantly increased overall in the cohort. A statistically significant excess of deaths was observed for colon and lung cancers in the entire cohort, SMR=2.7 (95% CI, 1.2-5.1), SMR=1.8 (95% CI, 1.1-2.7), respectively. Significant SMRs in the cohort as a whole were also observed for senile and pre-senile psychotic conditions (SMR=5.1, 95% CI, 1.4-13.1), and pneumonia (SMR=2.6, 95% CI, 1.3-4.8). An observed excess of subarachnoid hemorrhage was seen mainly in whites (SMR=10.1, 95% CI, 1.2-36.3). There was a suggestion of an excess of deaths from ischemic heart disease also, but the elevated SMR was confined to men and was not statistically significant. CONCLUSION: this study confirms the excess occurrence of lung and colon cancers, and stroke previously reported in this occupational group. New findings are the excess of risk for senile and pre-senile psychotic conditions and pneumonia, which together with the excess of colon cancer appear specific for pig/pork workers, as they were not evident in much larger studies of workers in abattoirs and processing plants handling cattle and sheep. However, caution should be exercised in interpreting these findings, since some of them could have occurred by chance, resulting from our examination of a large number of causes of death in multiple study subgroups. For the moment, the significance of these findings remains unknown until they are confirmed in larger studies of adequate statistical power. Studies that will take into account possible occupational and non-occupational confounding factors are needed. Copyright © 2011. Published by Elsevier Inc.\",\n \"title\": \"Mortality in workers employed in pig abattoirs and processing plants.\"\n },\n {\n \"docid\": \"MED-3280\",\n \"text\": \"Conventional chemotherapies have showed their limits, notably for patients with advanced cancer. New therapeutic strategies must be identified, and the metabolic abnormalities of cancer cells offer such opportunities. Many human cancer cell lines and primary tumors have absolute requirements for methionine, an essential amino acid. In contrast, normal cells are relatively resistant to exogenous methionine restriction. The biochemical mechanism for methionine dependency has been studied extensively, but the fundamental mechanism remains unclear. A number of investigators have attempted to exploit the methionine dependence of tumors for therapeutic effects in vivo. To reduce in vivo methionine in plasma and tumours, dietary and pharmacological treatments have been used. Methionine-free diet or methionine-deprived total parenteral nutrition causes regression of a variety of animal tumours. Alternatively, methionine depletion was achieved by the use of methioninase. This enzyme specifically degrades methionine and inhibits tumour growth in preclinical models. Because of potential toxicity and quality of life problems, prolonged methionine restriction with diet or with methioninase is not suitable for clinical use. Methionine restriction may find greater application in association with various chemotherapeutic agents. Several preclinical studies have demonstrated synergy between methionine restriction and various cytotoxic chemotherapy drugs. The experimental results accumulated during the last three decades suggest that methionine restriction can become an additional cancer therapeutic strategy, notably in association with chemotherapy.\",\n \"title\": \"Methionine dependency and cancer treatment.\"\n },\n {\n \"docid\": \"MED-3137\",\n \"text\": \"A longstanding goal of dietary surveillance has been to estimate the proportion of the population with intakes above or below a target, such as a recommended level of intake. However, until now, statistical methods for assessing the alignment of food intakes with recommendations have been lacking. The purposes of this study were to demonstrate the National Cancer Institute’s method of estimating the distribution of usual intake of foods and determine the proportion of the U.S. population who does not meet federal dietary recommendations. Data were obtained from the 2001–2004 NHANES for 16,338 persons, aged 2 y and older. Quantities of foods reported on 24-h recalls were translated into amounts of various food groups using the MyPyramid Equivalents Database. Usual dietary intake distributions were modeled, accounting for sequence effect, weekend/weekday effect, sex, age, poverty income ratio, and race/ethnicity. The majority of the population did not meet recommendations for all of the nutrient-rich food groups, except total grains and meat and beans. Concomitantly, overconsumption of energy from solid fats, added sugars, and alcoholic beverages (“empty calories”) was ubiquitous. Over 80% of persons age ≥71 y and over 90% of all other sex-age groups had intakes of empty calories that exceeded the discretionary calorie allowances. In conclusion, nearly the entire U.S. population consumes a diet that is not on par with recommendations. These findings add another piece to the rather disturbing picture that is emerging of a nation’s diet in crisis.\",\n \"title\": \"Americans Do Not Meet Federal Dietary Recommendations\"\n },\n {\n \"docid\": \"MED-4921\",\n \"text\": \"BACKGROUND & AIMS: The diagnostic criteria for celiac disease require small-bowel mucosal villous atrophy with crypt hyperplasia (Marsh III). However, mucosal damage develops gradually and patients may evince clinical symptoms before histologic changes appear. Endomysial antibodies are specific in predicting forthcoming villous atrophy. We hypothesized that patients with mild enteropathy but positive endomysial antibodies benefit from a gluten-free diet (GFD) similarly to patients with more severe enteropathy. METHODS: Small-bowel endoscopy together with clinical evaluations was performed in all together 70 consecutive adults with positive endomysial antibodies. Of these, 23 had only mild enteropathy (Marsh I-II) and they were randomized either to continue on a gluten-containing diet or start a GFD. After 1 year, clinical, serologic, and histologic evaluations were repeated. A total of 47 participants had small-bowel mucosal lesions compatible with celiac disease (Marsh III), and these served as disease controls. RESULTS: In the gluten-containing diet group (Marsh I-II) the small-bowel mucosal villous architecture deteriorated in all participants, and the symptoms and abnormal antibody titers persisted. In contrast, in the GFD group (Marsh I-II) the symptoms were alleviated, antibody titers decreased, and mucosal inflammation diminished equally to celiac controls (Marsh III). When the trial was completed, all participants chose to continue on a life-long GFD. CONCLUSIONS: Patients with endomysial antibodies benefit from a GFD regardless of the degree of enteropathy. The diagnostic criteria for celiac disease need re-evaluation: endomysial antibody positivity without atrophy belongs to the spectrum of genetic gluten intolerance, and warrants dietary treatment.\",\n \"title\": \"Diagnosing mild enteropathy celiac disease: a randomized, controlled clinical study.\"\n },\n {\n \"docid\": \"MED-1256\",\n \"text\": \"BACKGROUND: Limited consumption of red meat, including beef, is one of many often-suggested strategies to reduce the risk of coronary heart disease (CHD). However, the role that beef consumption specifically plays in promoting adverse changes in the cardiovascular risk factor profile is unclear. OBJECTIVE: A meta-analysis of randomized, controlled, clinical trials (RCTs) was conducted to evaluate the effects of beef, independent of other red and processed meats, compared with poultry and/or fish consumption, on lipoprotein lipids. METHODS: RCTs published from 1950 to 2010 were considered for inclusion. Studies were included if they reported fasting lipoprotein lipid changes after beef and poultry/fish consumption by subjects free of chronic disease. A total of 124 RCTs were identified, and 8 studies involving 406 subjects met the prespecified entry criteria and were included in the analysis. RESULTS: Relative to the baseline diet, mean ± standard error changes (in mg/dL) after beef versus poultry/fish consumption, respectively, were -8.1 ± 2.8 vs. -6.2 ± 3.1 for total cholesterol (P = .630), -8.2 ± 4.2 vs. -8.9 ± 4.4 for low-density lipoprotein cholesterol (P = .905), -2.3 ± 1.0 vs. -1.9 ± 0.8 for high-density lipoprotein cholesterol (P = .762), and -8.1 ± 3.6 vs. -12.9 ± 4.0 mg/dL for triacylglycerols (P = .367). CONCLUSION: Changes in the fasting lipid profile were not significantly different with beef consumption compared with those with poultry and/or fish consumption. Inclusion of lean beef in the diet increases the variety of available food choices, which may improve long-term adherence with dietary recommendations for lipid management. Copyright © 2012 National Lipid Association. Published by Elsevier Inc. All rights reserved.\",\n \"title\": \"A meta-analysis of randomized controlled trials that compare the lipid effects of beef versus poultry and/or fish consumption.\"\n },\n {\n \"docid\": \"MED-4680\",\n \"text\": \"OBJECTIVE: To investigate associations between dietary intakes throughout childhood and age at menarche, a possible indicator of future risk of disease, in a contemporary cohort of British girls. DESIGN: Diet was assessed by FFQ at 3 and 7 years of age, and by a 3 d unweighed food diary at 10 years. Age at menarche was categorised as before or after 12 years 8 months, a point close to the median age in this cohort. SETTING: Bristol, South-West England. SUBJECTS: Girls (n 3298) participating in the Avon Longitudinal Study of Parents and Children. RESULTS: Higher energy intakes at 10 years were positively associated with the early occurrence of menarche, but this association was removed on adjusting for body size. Total and animal protein intakes at 3 and 7 years were positively associated with age at menarche ≤12 years 8 months (adjusted OR for a 1 sd increase in protein at 7 years: 1·14 (95 % CI 1·04, 1·26)). Higher PUFA intakes at 3 and 7 years were also positively associated with early occurrence of menarche. Meat intake at 3 and 7 years was strongly positively associated with reaching menarche by 12 years 8 months (OR for menarche in the highest v. lowest category of meat consumption at 7 years: 1·75 (95 % CI 1·25, 2·44)). CONCLUSIONS: These data suggest that higher intakes of protein and meat in early to mid-childhood may lead to earlier menarche. This may have implications for the lifetime risk of breast cancer and osteoporosis.\",\n \"title\": \"Diet throughout childhood and age at menarche in a contemporary cohort of British girls.\"\n },\n {\n \"docid\": \"MED-3244\",\n \"text\": \"Diet may represent a modifiable prostate cancer (CaP) risk factor, but a vegetable-based prostate-healthy diet is a major change for most men. We used a ratio of animal:vegetable proteins (A:V ratio) to evaluate whether a comprehensive dietary change was self-sustaining following completion of 11 weekly dietary and cooking classes that integrated mindfulness training (MT). Thirty-six men with recurring CaP were randomized to the intervention or wait-list control. Assessments were at baseline, three months and six months. Of the 17 men randomized to the intervention, 14 completed the requirements. Nineteen were randomized to control and 17 completed requirements. Compared to controls, a significant post-intervention (3 months) decrease in A:V ratio in the intervention group (p=.01) was self-maintained 3 months post-intervention (p=0.049). At each assessment, the A:V ratio was correlated with lycopene, fiber, saturated fat, and dietary cholesterol; four dietary components linked to clinically relevant outcomes in CaP. Change in A:V ratio was also significantly correlated with changes in fiber, saturated fat and dietary cholesterol intake. Participants reported regular MT practice and there was a significant correlation between MT practice and changes in both initiation and maintenance of the change in the A:V ratio. These pilot results provide encouraging evidence for the feasibility of a dietary program that includes MT in supporting dietary change for men with recurrent CaP and invite further study to explore the possible role of MT as a means of supporting both initiation of dietary changes and maintenance of those changes over time.\",\n \"title\": \"A Novel Measure of Dietary Change in a Prostate Cancer Dietary Program Incorporating Mindfulness Training\"\n },\n {\n \"docid\": \"MED-1230\",\n \"text\": \"This study examined the relationship between funding sources and the outcomes of published obesity-related research. A list of funded projects for human nutrition research linking food intake to obesity in 2001-2005 was drawn from two distinct sources: (a) the federal government's semi-public generic commodity promotion or \\\"checkoff\\\" programs for Fluid Milk and Dairy and (b) the National Institutes of Health (NIH). The Principal Investigator for each funded project was determined. Published literature by that individual was located using an Ovid MEDLINE and PubMed author search. All articles related to both dairy and obesity were included. Financial sponsorship for each article and article conclusions were classified by independent groups of co-investigators. Seventy-nine relevant articles were included in the study. Of these, 62 were sponsored by the checkoff programs and 17 by the NIH. The study did not find consistent evidence that checkoff-funded projects were more likely to support an obesity prevention benefit from dairy consumption. The study did identify a new research methodology for the investigation of bias by source of sponsorship. Copyright © 2012 Elsevier Inc. All rights reserved.\",\n \"title\": \"Relationship between funding sources and outcomes of obesity-related research.\"\n },\n {\n \"docid\": \"MED-3000\",\n \"text\": \"An increased risk for colorectal cancer has been consistently reported for long-time consumption of cooked and processed red meat. This has frequently been attributed to chemical carcinogens arising during the cooking process of meat. Long-time fish or poultry consumption apparently does not increase the risk, although similar or higher concentrations of chemical carcinogens were recorded in their preparation for consumption. The geographic epidemiology of colorectal cancer seems to correspond to regions with a high rate of beef consumption. Countries with a virtual absence of beef in the diet (India) or where preferably lamb or goat meat is consumed (several Arabic countries) reveal low rates of colorectal cancer. In China, pork consumption has a long tradition, with an intermediate colorectal cancer rate. In Japan and Korea, large scale beef and pork imports started after World War II or after the Korean War. A steep rise in colorectal cancer incidence was noted after 1970 in Japan and 1990 in Korea. The consumption of undercooked beef (e.g., shabu-shabu, Korean yukhoe and Japanese yukke) became very popular in both countries. The available data are compatible with the interpretation that a specific beef factor, suspected to be one or more thermoresistant potentially oncogenic bovine viruses (e.g., polyoma-, papilloma- or possibly single-stranded DNA viruses) may contaminate beef preparations and lead to latent infections in the colorectal tract. Preceding, concomitant or subsequent exposure to chemical carcinogens arising during cooking procedures should result in increased risk for colorectal cancer synergistic with these infections. Copyright © 2011 UICC.\",\n \"title\": \"Red meat consumption and cancer: reasons to suspect involvement of bovine infectious factors in colorectal cancer.\"\n },\n {\n \"docid\": \"MED-3274\",\n \"text\": \"Objective To determine whether dogs can be trained to identify people with bladder cancer on the basis of urine odour more successfully than would be expected by chance alone. Design Experimental, “proof of principle” study in which six dogs were trained to discriminate between urine from patients with bladder cancer and urine from diseased and healthy controls and then evaluated in tests requiring the selection of one bladder cancer urine sample from six controls. Participants 36 male and female patients (age range 48-90 years) presenting with new or recurrent transitional cell carcinoma of the bladder (27 samples used for training; 9 used for formal testing); 108 male and female controls (diseased and healthy, age range 18-85 years—54 samples used in training; 54 used for testing). Main outcome measure Mean proportion of successes per dog achieved during evaluation, compared with an expected value of 1 in 7 (14%). Results Taken as a group, the dogs correctly selected urine from patients with bladder cancer on 22 out of 54 occasions. This gave a mean success rate of 41% (95% confidence intervals 23% to 58% under assumptions of normality, 26% to 52% using bootstrap methods), compared with 14% expected by chance alone. Multivariate analysis suggested that the dogs' capacity to recognise a characteristic bladder cancer odour was independent of other chemical aspects of the urine detectable by urinalysis. Conclusions Dogs can be trained to distinguish patients with bladder cancer on the basis of urine odour more successfully than would be expected by chance alone. This suggests that tumour related volatile compounds are present in urine, imparting a characteristic odour signature distinct from those associated with secondary effects of the tumour, such as bleeding, inflammation, and infection.\",\n \"title\": \"Olfactory detection of human bladder cancer by dogs: proof of principle study\"\n },\n {\n \"docid\": \"MED-2469\",\n \"text\": \"The intestinal flora is considered to have an impact on the development of the immune system. In the anthroposophic lifestyle, a diet comprising vegetables spontaneously fermented by lactobacilli, and a restrictive use of antibiotics, anti-pyretics and vaccinations, is typical. The aim of this study was to assess the gut flora in infants in relation to certain lifestyle characteristics associated with anthroposophy. Sixty-nine children < 2 years of age with an anthroposophic lifestyle, and 59 infants of a similar age with a traditional lifestyle, were clinically examined and questionnaire replies assessed. Fecal samples were analyzed by bacterial enumeration, bacterial typing through biochemical fingerprinting and by measuring microflora-associated characteristics (MACs). The numbers of colony-forming units (CFU)/g of feces were significantly higher for enterococci and lactic acid bacteria in children who had never been exposed to antibiotics (5.5 x 107 vs. 2.1 x 107; p < 0.001 and 10 x 107 vs. 4.1 x 107; p < 0.01, respectively). Furthermore, the number of enterococci was significantly higher in breastfed and vegetarian infants (p < 0.01). The diversity (Simpson's diversity index) of lactobacilli, as determined by biochemical fingerprinting, was higher in infants born at home than in those born in hospital (p < 0.01). Several MACs were related to specific lifestyle features, and infants with an anthroposophic lifestyle had a higher proportion of acetic acid and a lower proportion of propionic acid in their stool as compared to the control children. In conclusion, lifestyle factors related to the anthroposophic way of life influenced the composition of the gut flora in the infants. These differences may contribute to the lower prevalence of atopic disease previously observed in children in anthroposophic families.\",\n \"title\": \"An anthroposophic lifestyle and intestinal microflora in infancy.\"\n },\n {\n \"docid\": \"MED-3785\",\n \"text\": \"PURPOSE: Components of one-carbon metabolism are believed to influence cancer development with suggested mechanisms, including DNA methylation and DNA repair mechanisms. However, few prospective studies have investigated one-carbon metabolism in relation to prostate cancer risk, and the results have been conflicting. The aim of this study was to do a comprehensive investigation of the components of one-carbon metabolism in relation to prostate cancer risk. A panel of seven circulating B vitamins and related metabolites was selected, most of which have not been studied before. MATERIALS AND METHODS: We analyzed plasma concentrations of betaine, choline, cysteine, methionine, methylmalonic acid (MMA), vitamin B2, and vitamin B6 in 561 cases and 1,034 controls matched for age and recruitment date, nested within the population-based Northern Sweden Health and Disease Cohort. Relative risks of prostate cancer were estimated by conditional logistic regression. RESULTS: Positive associations with prostate cancer risk were observed for choline and vitamin B2, and an inverse association was observed for MMA. The relative risks for a doubling in concentrations were 1.46 [95% confidence interval (95% CI), 1.04-2.05; P(trend) = 0.03] for choline, 1.11 (95% CI, 1.00-1.23; P(trend) = 0.04) for vitamin B2, and 0.78 (95% CI, 0.63-0.97; P(trend) = 0.03) for MMA. Concentrations of betaine, cysteine, methionine, and vitamin B6 were not associated with prostate cancer risk. CONCLUSION: The results of this large prospective study suggest that elevated plasma concentrations of choline and vitamin B2 may be associated with an increased risk of prostate cancer. These novel findings support a role of one-carbon metabolism in prostate cancer etiology and warrant further investigation.\",\n \"title\": \"One-carbon metabolism and prostate cancer risk: prospective investigation of seven circulating B vitamins and metabolites.\"\n },\n {\n \"docid\": \"MED-3350\",\n \"text\": \"Normotensive adults on low-sodium, weight-loss, and control diets recorded preferences and perceived saltiness for sodium chloride (NaCl) added to cream soup at intervals over 1 yr. Reduction in sodium intake and excretion accompanied a shift in preference toward less salt: preferred concentrations by ad libitum salting declined from 0.72% at the onset to 0.33% NaCl at week 24; hedonic scores for high concentrations of NaCl decreased significantly while scores for low concentrations increased. After 3 mo of sodium restriction, NaCl preferences readjusted to a lower level: ad libitum additions of NaCl were similar after 13, 24, and 52 wk. Less hedonic variation was observed among controls than among Na-restricted groups. The weight-loss group showed increased liking for mid-range NaCl levels. Mechanisms underlying preference changes, including physiological, behavioral, and context effects, may provide insights into maintenance of low-sodium diets for treatment and prevention of hypertension.\",\n \"title\": \"Effect of dietary sodium restriction on taste responses to sodium chloride: a longitudinal study.\"\n },\n {\n \"docid\": \"MED-1720\",\n \"text\": \"BACKGROUND: Insulin-like growth factor (IGF)-I and its main binding protein, IGFBP-3, modulate cell growth and survival, and are thought to be important in tumour development. Circulating concentrations of IGF-I might be associated with an increased risk of cancer, whereas IGFBP-3 concentrations could be associated with a decreased cancer risk. METHODS: We did a systematic review and meta-regression analysis of case-control studies, including studies nested in cohorts, of the association between concentrations of IGF-I and IGFBP-3 and prostate, colorectal, premenopausal and postmenopausal breast, and lung cancer. Study-specific dose-response slopes were obtained by relating the natural log of odds ratios for different exposure levels to blood concentrations normalised to a percentile scale. FINDINGS: We identified 21 eligible studies (26 datasets), which included 3609 cases and 7137 controls. High concentrations of IGF-I were associated with an increased risk of prostate cancer (odds ratio comparing 75th with 25th percentile 1.49, 95% CI 1.14-1.95) and premenopausal breast cancer (1.65, 1.26-2.08) and high concentrations of IGFBP-3 were associated with increased risk of premenopausal breast cancer (1.51, 1.01-2.27). Associations were larger in assessments of plasma samples than in serum samples, and in standard case-control studies compared with nested studies. INTERPRETATION: Circulating concentrations of IGF-I and IGFBP-3 are associated with an increased risk of common cancers, but associations are modest and vary between sites. Although laboratory methods need to be standardised, these epidemiological observations could have major implications for assessment of risk and prevention of cancer.\",\n \"title\": \"Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis.\"\n },\n {\n \"docid\": \"MED-2517\",\n \"text\": \"Many experts in the biology of ageing believe that pharmacological interventions to slow ageing are a matter of ‘when’ rather than ‘if’. A leading target for such interventions is the nutrient response pathway defined by the mechanistic target of rapamycin (mTOR). Inhibition of this pathway extends lifespan in model organisms and confers protection against a growing list of age-related pathologies. Characterized inhibitors of this pathway are already clinically approved, and others are under development. Although adverse side effects currently preclude use in otherwise healthy individuals, drugs that target the mTOR pathway could one day become widely used to slow ageing and reduce age-related pathologies in humans.\",\n \"title\": \"mTOR is a key modulator of ageing and age-related disease\"\n },\n {\n \"docid\": \"MED-4831\",\n \"text\": \"Dyslipidemia is a primary risk factor for cardiovascular disease, peripheral vascular disease, and stroke. Current guidelines recommend diet as first-line therapy for patients with elevated plasma cholesterol concentrations. However, what constitutes an optimal dietary regimen remains a matter of controversy. Large prospective trials have demonstrated that populations following plant-based diets, particularly vegetarian and vegan diets, are at lower risk for ischemic heart disease mortality. The investigators therefore reviewed the published scientific research to determine the effectiveness of plant-based diets in modifying plasma lipid concentrations. Twenty-seven randomized controlled and observational trials were included. Of the 4 types of plant-based diets considered, interventions testing a combination diet (a vegetarian or vegan diet combined with nuts, soy, and/or fiber) demonstrated the greatest effects (up to 35% plasma low-density lipoprotein cholesterol reduction), followed by vegan and ovolactovegetarian diets. Interventions allowing small amounts of lean meat demonstrated less dramatic reductions in total cholesterol and low-density lipoprotein levels. In conclusion, plant-based dietary interventions are effective in lowering plasma cholesterol concentrations.\",\n \"title\": \"Effects of plant-based diets on plasma lipids.\"\n },\n {\n \"docid\": \"MED-3143\",\n \"text\": \"BACKGROUND: Olestra is a nonabsorbable, energy-free fat substitute. Because it is not absorbed, it may cause digestive symptoms when consumed in large amounts. OBJECTIVE: To compare the frequency and impact of gastrointestinal symptoms in adults and children who freely consume snacks containing olestra or regular snacks in the home. DESIGN: 6-week, double-blind, randomized, parallel, placebo-controlled trial. SETTING: General community. PARTICIPANTS: 3181 volunteers 2 to 89 years of age. INTERVENTION: Households received identical packages labeled as containing olestra corn or potato chips. These packages contained either olestra or regular chips (control). MEASUREMENT: Gastrointestinal symptoms and their impact on daily activities were reported in a daily record. RESULTS: At least one gastrointestinal symptom was reported by 619 of 1620 (38.2%) persons in the olestra group and 576 of 1561 (36.9%) controls (difference, 1.3 percentage points [95% CI, -3.6 to 6.2 percentage points]; P = 0.60). In general, the groups did not differ significantly in the proportion of participants who reported individual gastrointestinal symptoms; however, more controls reported nausea (8.4% compared with 5.7%; difference, -2.7 percentage points [CI, -4.9 to -0.4 percentage points]; P = 0.02). The only difference between groups for the mean numbers of days on which symptoms were reported was that participants in the olestra group had 1 more symptom-day of more frequent bowel movements than did controls (3.7 symptom-days compared with 2.8 symptom days; difference, 0.9 symptom-days [CI, 0.1 to 1.8 symptom-days]; P = 0.04). The groups did not differ in the impact of symptoms on daily activities. CONCLUSIONS: Clinically meaningful or bothersome gastrointestinal effects are not associated with unregulated consumption of olestra corn and potato chips in the home.\",\n \"title\": \"Gastrointestinal symptoms in 3181 volunteers ingesting snack foods containing olestra or triglycerides. A 6-week randomized, placebo-controlled trial.\"\n },\n {\n \"docid\": \"MED-4261\",\n \"text\": \"BACKGROUND: Meat intake may be related to weight gain because of its high energy and fat content. Some observational studies have shown that meat consumption is positively associated with weight gain, but intervention studies have shown mixed results. OBJECTIVE: Our objective was to assess the association between consumption of total meat, red meat, poultry, and processed meat and weight gain after 5 y of follow-up, on average, in the large European population who participated in the European Prospective Investigation into Cancer and Nutrition-Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating Out of Home and Obesity (EPIC-PANACEA) project. DESIGN: A total of 103,455 men and 270,348 women aged 25-70 y were recruited between 1992 and 2000 in 10 European countries. Diet was assessed at baseline with the use of country-specific validated questionnaires. A dietary calibration study was conducted in a representative subsample of the cohort. Weight and height were measured at baseline and self-reported at follow-up in most centers. Associations between energy from meat (kcal/d) and annual weight change (g/y) were assessed with the use of linear mixed models, controlled for age, sex, total energy intake, physical activity, dietary patterns, and other potential confounders. RESULTS: Total meat consumption was positively associated with weight gain in men and women, in normal-weight and overweight subjects, and in smokers and nonsmokers. With adjustment for estimated energy intake, an increase in meat intake of 250 g/d (eg, one steak at approximately 450 kcal) would lead to a 2-kg higher weight gain after 5 y (95% CI: 1.5, 2.7 kg). Positive associations were observed for red meat, poultry, and processed meat. CONCLUSION: Our results suggest that a decrease in meat consumption may improve weight management.\",\n \"title\": \"Meat consumption and prospective weight change in participants of the EPIC-PANACEA study.\"\n },\n {\n \"docid\": \"MED-2830\",\n \"text\": \"OBJECTIVE: The aim of this work was to determine the bioavailability of herbs and spices after human consumption by measuring the ability to protect lymphocytes from an oxidative injury and by examining the impact on inflammatory biomarkers in activated THP-1 cells. METHODS: Ten to 12 subjects in each of 13 groups consumed a defined amount of herb or spice for 7 days. Blood was drawn from subjects before consumption and 1 hour after taking the final herb or spice capsules. Subject serum and various extractions of the herbs and spices were analyzed for antioxidant capacity by oxygen radical absorbance capacity (ORAC) analysis or by 1,1-diphenyl-2-picrylhydrzyl (DPPH). Subject peripheral blood mononuclear cells (PBMCs) in medium with10% autologous serum were incubated with hydrogen peroxide to induce DNA strand breaks. Subject serum was also used to treat activated THP-1 cells to determine relative quantities of 3 inflammatory cytokine (tumor necrosis factor-α [TNF-α], interleukin-1α [IL-1α], and IL-6) mRNAs. RESULTS: Herbs and spices that protected PBMCs against DNA strand breaks were paprika, rosemary, ginger, heat-treated turmeric, sage, and cumin. Paprika also appeared to protect cells from normal apoptotic processes. Of the 3 cytokine mRNAs studied (TNF-α, IL-1α, and IL-6), TNF-α was the most sensitive responder to oxidized LDL-treated macrophages. Clove, ginger, rosemary, and turmeric were able to significantly reduce oxidized LDL-induced expression of TNF-α. Serum from those consuming ginger reduced all three inflammatory biomarkers. Ginger, rosemary, and turmeric showed protective capacity by both oxidative protection and inflammation measures. CONCLUSIONS: DNA strand breaks and inflammatory biomarkers are a good functional measure of a food's bioavailability.\",\n \"title\": \"Bioavailability of herbs and spices in humans as determined by ex vivo inflammatory suppression and DNA strand breaks.\"\n },\n {\n \"docid\": \"MED-2209\",\n \"text\": \"This study investigated the effect of different traditional cooking methods on glycemic index (GI) and glycemic response of ten Sweet potato (Ipomoea batatas) cultivars commonly eaten in Jamaica. Matured tubers were cooked by roasting, baking, frying, or boiling then immediately consumed by the ten nondiabetic test subjects (5 males and 5 females; mean age of 27 ± 2 years). The GI varied between 41 ± 5–93 ± 5 for the tubers studied. Samples prepared by boiling had the lowest GI (41 ± 5–50 ± 3), while those processed by baking (82 ± 3–94 ± 3) and roasting (79 ± 4–93 ± 2) had the highest GI values. The study indicates that the glycemic index of Jamaican sweet potatoes varies significantly with the method of preparation and to a lesser extent on intravarietal differences. Consumption of boiled sweet potatoes could minimize postprandial blood glucose spikes and therefore, may prove to be more efficacious in the management of type 2 diabetes mellitus.\",\n \"title\": \"Relationship between Processing Method and the Glycemic Indices of Ten Sweet Potato (Ipomoea batatas) Cultivars Commonly Consumed in Jamaica\"\n },\n {\n \"docid\": \"MED-3242\",\n \"text\": \"Previous studies have suggested that dietary factors may be important in the development of bladder cancer. We examined macronutrient intake in relation to risk of urothelial cell carcinoma among 469,339 men and women in the European Prospective Investigation into Cancer and Nutrition. Associations were examined using Cox regression, stratified by sex, age at recruitment and centre and further adjusted for smoking status and duration, body mass index and total energy intake. After an average of 11.3 years of follow-up, 1,416 new cases of urothelial cell carcinoma were identified. After allowing for measurement error, a 3% increase in the consumption of energy intake from animal protein was associated with a 15% higher risk (95% confidence interval [CI]: 3-30%; p(trend) = 0.01) and a 2% increase in energy from plant protein intake was associated with a 23% lower risk (95% CI: 36-7%, p(trend) = 0.006). Dietary intake of fat, carbohydrate, fibre or calcium was not associated with risk. These findings suggest that animal and/or plant protein may affect the risk of urothelial cell carcinoma, and examination of these associations in other studies is needed. Copyright © 2012 UICC.\",\n \"title\": \"Macronutrient intake and risk of urothelial cell carcinoma in the European prospective investigation into cancer and nutrition.\"\n },\n {\n \"docid\": \"MED-4258\",\n \"text\": \"The objective of the present study was to assess animal and plant protein intakes in the Belgian population and to examine their relationship with overweight and obesity (OB). The subjects participated in the Belgian National Food Consumption Survey conducted in 2004. Food consumption was assessed by using two non-consecutive 24 h dietary recalls. About 3083 participants ( ≥ 15 years of age; 1546 males, 1537 females) provided completed dietary information. Animal protein intake (47 g/d) contributed more to total protein intakes of 72 g/d than plant protein intake, which accounted for 25 g/d. Meat and meat products were the main contributors to total animal protein intakes (53 %), whereas cereals and cereal products contributed most to plant protein intake (54 %). Males had higher animal and plant protein intakes than females (P < 0·001). Legume and soya protein intakes were low in the whole population (0·101 and 0·174 g/d, respectively). In males, animal protein intake was positively associated with BMI (β = 0·013; P = 0·001) and waist circumference (WC; β = 0·041; P = 0·002). Both in males and females, plant protein intake was inversely associated with BMI (males: β = - 0·036; P < 0·001; females: β = - 0·046; P = 0·001) and WC (male: β = - 0·137; P < 0·001; female: β = - 0·096; P = 0·024). In conclusion, plant protein intakes were lower than animal protein intakes among a representative sample of the Belgian population and decreased with age. Associations with anthropometric data indicated that plant proteins could offer a protective effect in the prevention of overweight and OB in the Belgian population.\",\n \"title\": \"Plant and animal protein intake and its association with overweight and obesity among the Belgian population.\"\n },\n {\n \"docid\": \"MED-3455\",\n \"text\": \"Exercise-induced deoxyribonucleic acid (DNA) damage is often associated with an increase in free radicals; however, there is a lack of evidence examining the two in parallel. This study tested the hypothesis that high-intensity exercise has the ability to produce free radicals that may be capable of causing DNA damage. Twelve apparently healthy male subjects (age: 23 ± 4 years; stature: 181 ± 8 cm; body mass: 80 ± 9 kg; and VO(2max) : 49 ± 5 ml/kg/min) performed three 5 min consecutive and incremental stages (40, 70, and 100% of VO(2max) ) of aerobic exercise with a 15-min period separating each stage. Blood was drawn after each bout of exercise for the determination of ex vivo free radicals, DNA damage, protein carbonyls, lipid hydroperoxide (LOOH) concentration, and a range of lipid-soluble antioxidants. Lipid-derived oxygen-centered free radicals (hyperfine coupling constants a(Nitrogen) = 13.7 Gauss (G) and aβ(Hydrogen) = 1.8 G) increased as a result of acute moderate and high-intensity exercise (P < 0.05), while DNA damage was also increased (P < 0.05). Systemic changes were observed in LOOH and for lipid-soluble antioxidants throughout exercise (P < 0.05); however, there was no observed change in protein carbonyl concentration (P > 0.05). These findings identify lipid-derived free radical species as possible contributors to peripheral mononuclear cell DNA damage in the human exercising model. This damage occurs in the presence of lipid oxidation but in the absence of any change to protein carbonyl concentration. The significance of these findings may have relevance in terms of immune function, the aging process, and the pathology of carcinogenesis. Copyright © 2010 Wiley-Liss, Inc.\",\n \"title\": \"Exercise-induced lipid peroxidation: Implications for deoxyribonucleic acid damage and systemic free radical generation.\"\n },\n {\n \"docid\": \"MED-4049\",\n \"text\": \"More than 85% of breast cancers are sporadic and attributable to long-term exposure to environmental carcinogens, such as those in the diet, through a multistep disease process progressing from non-cancerous to premalignant and malignant stages. The chemical carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is one of the most abundant heterocyclic amines found in high-temperature cooked meats and is recognized as a mammary carcinogen. However, the PhIP’s mechanism of action in breast cell carcinogenesis is not clear. Here, we demonstrated, for the first time, that cumulative exposures to PhIP at physiologically achievable, pico to nanomolar concentrations effectively induced progressive carcinogenesis of human breast epithelial MCF10A cells from a non-cancerous stage to premalignant and malignant stages in a dose- and exposure-dependent manner. Progressive carcinogenesis was measured by increasingly- acquired cancer-associated properties of reduced dependence on growth factors, anchorage-independent growth, acinar-conformational disruption, proliferation, migration, invasion, tumorigenicity with metastasis and increased stem-like cell populations. These biological changes were accompanied by biochemical and molecular changes, including upregulated H-Ras gene expression, extracellular signal-regulated kinase (ERK) pathway activation, Nox-1 expression, reactive oxygen species (ROS) elevation, increased HIF-1α, Sp1, tumor necrosis factor-α, matrix metalloproteinase (MMP)-2, MMP-9, aldehyde dehydrogenase activity and reduced E-cadherin. The Ras-ERK-Nox-ROS pathway played an important role in not only initiation but also maintenance of cellular carcinogenesis induced by PhIP. Using biological, biochemical and molecular changes as targeted endpoints, we identified that the green tea catechin components epicatechin-3-gallate and epigallocatechin-3-gallate, at non-cytotoxic doses, were capable of suppressing PhIP-induced cellular carcinogenesis and tumorigenicity.\",\n \"title\": \"Intervention of human breast cell carcinogenesis chronically induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine\"\n },\n {\n \"docid\": \"MED-3273\",\n \"text\": \"Recent studies confirm that dietary methionine restriction increases both mean and maximal lifespan in rats and mice, achieving \\\"aging retardant\\\" effects very similar to those of caloric restriction, including a suppression of mitochondrial superoxide generation. Although voluntary caloric restriction is never likely to gain much popularity as a pro-longevity strategy for humans, it may be more feasible to achieve moderate methionine restriction, in light of the fact that vegan diets tend to be relatively low in this amino acid. Plant proteins - especially those derived from legumes or nuts - tend to be lower in methionine than animal proteins. Furthermore, the total protein content of vegan diets, as a function of calorie content, tends to be lower than that of omnivore diets, and plant protein has somewhat lower bioavailability than animal protein. Whole-food vegan diets that moderate bean and soy intake, while including ample amounts of fruit and wine or beer, can be quite low in methionine, while supplying abundant nutrition for health (assuming concurrent B12 supplementation). Furthermore, low-fat vegan diets, coupled with exercise training, can be expected to promote longevity by decreasing systemic levels of insulin and free IGF-I; the latter effect would be amplified by methionine restriction - though it is not clear whether IGF-I down-regulation is the sole basis for the impact of low-methionine diets on longevity in rodents.\",\n \"title\": \"The low-methionine content of vegan diets may make methionine restriction feasible as a life extension strategy.\"\n },\n {\n \"docid\": \"MED-3359\",\n \"text\": \"Background Fruit and vegetable consumption and ingestion of carotenoids have been found to be associated with human skin-color (yellowness) in a recent cross-sectional study. This carotenoid-based coloration contributes beneficially to the appearance of health in humans and is held to be a sexually selected cue of condition in other species. Methodology and Principal Findings Here we investigate the effects of fruit and vegetable consumption on skin-color longitudinally to determine the magnitude and duration of diet change required to change skin-color perceptibly. Diet and skin-color were recorded at baseline and after three and six weeks, in a group of 35 individuals who were without makeup, self-tanning agents and/or recent intensive UV exposure. Six-week changes in fruit and vegetable consumption were significantly correlated with changes in skin redness and yellowness over this period, and diet-linked skin reflectance changes were significantly associated with the spectral absorption of carotenoids and not melanin. We also used psychophysical methods to investigate the minimum color change required to confer perceptibly healthier and more attractive skin-coloration. Modest dietary changes are required to enhance apparent health (2.91 portions per day) and attractiveness (3.30 portions). Conclusions Increased fruit and vegetable consumption confers measurable and perceptibly beneficial effects on Caucasian skin appearance within six weeks. This effect could potentially be used as a motivational tool in dietary intervention.\",\n \"title\": \"You Are What You Eat: Within-Subject Increases in Fruit and Vegetable Consumption Confer Beneficial Skin-Color Changes\"\n },\n {\n \"docid\": \"MED-2656\",\n \"text\": \"The aim of previous research into the causes of allergic diseases, including asthma was mostly to identify potential risk factors in the environment. No major risk factors have been identified, however. Over the past 10 years, focus has, therefore, more been directed towards protective factors that could enhance the development of tolerance to allergens which were previously encountered early in life, but are now lost in modern affluent societies. In particular, the role of childhood infections has been discussed, but so far these studies have not been conclusive. Recent epidemiological studies and experimental research suggest that the microbial environment and exposure to microbial products in infancy modifies immune responses and enhances the development of tolerance to ubiquitous allergens. The intestinal microflora may play a particular role in this respect, as it is the major external driving force in the maturation of the immune system after birth, and animal experiments have shown it to be a prerequisite for normal development of oral tolerance. Recent studies have shown differences in the composition of the microflora between healthy and allergic infants in countries with a high and low prevalence of allergies and between healthy and allergic infants within such countries. These differences are apparent within the first week of life and thus precede clinical symptoms. The use of live microorganisms that might be beneficial to health has a long tradition and the safety is well documented. Very recently, several prospective intervention studies, modifying the gut flora from birth have yielded encouraging results and may suggest a new mode of primary prevention of allergy in the future.\",\n \"title\": \"Effects of intestinal microflora and the environment on the development of asthma and allergy.\"\n },\n {\n \"docid\": \"MED-3535\",\n \"text\": \"Cherries, and in particular sweet cherries, are a nutritionally dense food rich in anthocyanins, quercetin, hydroxycinnamates, potassium, fiber, vitamin C, carotenoids, and melatonin. UV concentration, degree of ripeness, postharvest storage conditions, and processing, each can significantly alter the amounts of nutrients and bioactive components. These constituent nutrients and bioactive food components support the potential preventive health benefits of cherry intake in relation to cancer, cardiovascular disease, diabetes, inflammatory diseases, and Alzheimer's disease. Mechanistically, cherries exhibit relatively high antioxidant activity, low glycemic response, COX 1 and 2 enzyme inhibition, and other anti-carcinogenic effects in vitro and in animal experiments. Well-designed cherry feeding studies are needed to further substantiate any health benefits in humans.\",\n \"title\": \"Cherries and health: a review.\"\n },\n {\n \"docid\": \"MED-3876\",\n \"text\": \"BACKGROUND: Chinese men have lower incidences of prostate cancer compared to men from Europe and North America. Asians consume large quantities of soya, a rich source of isoflavanoids phyto-oestrogens and have high plasma and urinary levels of these compounds. The mammalian lignans, enterolactone and enterodiol, are another group of weak plant oestrogens and are derived from seeds, cereals and grains. Vegetarians have high plasma and urinary concentrations of lignans. METHODS: The concentrations lignans and isoflavonic phyto-oestrogens were determined by gas chromatography-mass spectrometry (GC-MS) in plasma and prostatic fluid from Portuguese, Chinese and British men consuming their traditional diets. RESULTS: In prostatic fluid the mean concentrations of enterolactone were 31, 162 and 20.3 ng/ml for Hong Kong, Portugal and Britain respectively. Very high levels of enterolactone (> 600 ng/ml) were observed in the prostatic fluid of some of the men from Portugal. High concentrations of equol (3270 ng/ml) and daidzein (532 ng/ml) were found in a sample of prostatic fluid from Hong Kong. Higher mean levels of daidzein were observed in prostatic fluid from Hong Kong at 70 ng/ml, compared to 4.6 and 11.3 ng/ml in samples from Portugal and Britain respectively. Mean levels of daidzein were higher in the plasma samples from Hong Kong (31.3 ng/ml) compared to those from Portugal (1.3 ng/ml) and Britain (8.2 ng/ml). In general, the mean plasma concentrations of enterolactone from the three centres were similar, at 6.2, 3.9 and 3.9 ng/ml in samples from Hong Kong Portugal and Britain respectively. CONCLUSIONS: Higher concentrations of the isoflavanoid phyto-oestrogens, daidzein and equol, were found in the plasma and prostatic fluid of men from Hong Kong compared to those from Britain and Portugal. However, the levels of the lignan, enterolactone, were very much higher in prostatic fluid of Portuguese men. Isoflavanoids and lignans have many interesting properties and may, in part, be responsible for lower incidences of prostate cancer in men from Asia and also some Mediterranean countries. The isoflavanoids from soya, which are present in high concentrations in the prostatic fluid of Asian men, may be protective against prostate disease.\",\n \"title\": \"Lignans and isoflavonoids in plasma and prostatic fluid in men: samples from Portugal, Hong Kong, and the United Kingdom.\"\n },\n {\n \"docid\": \"MED-2513\",\n \"text\": \"Over the last several years, new evidence has kept pouring in about the remarkable effect of caloric restriction (CR) on the conspicuous bedfellows- aging and cancer. Through the use of various animal models, it is now well established that by reducing calorie intake one can not only increase life span but, also, lower the risk of various age related diseases such as cancer. Cancer cells are believed to be more dependent on glycolysis for their energy requirements than normal cells and, therefore, can be easily targeted by alteration in the energy-metabolic pathways, a hallmark of CR. Apart from inhibiting the growth of transplantable tumors, CR has been also shown to inhibit the development of spontaneous, radiation, and chemically induced tumors. The question regarding the potentiality of the anti-tumor effect of CR in humans has been in part answered by the resistance of a cohort of women, who had suffered from anorexia in their early life, to breast cancer. However, human research on the beneficial effect of CR is still at an early stage and needs further validation. Though the complete mechanism of the anti-tumor effect of CR is far from clear, the plausible involvement of nutrient sensing pathways or IGF-1 pathways proposed for its anti-aging action cannot be overruled. In fact, cancer cell lines, mutant for proteins involved in IGF-1 pathways, failed to respond to CR. In addition, CR decreases the levels of many growth factors, anabolic hormones, inflammatory cytokines, and oxidative markers that are deregulated in several cancers. In this review, we discuss the anti-tumor effect of CR, describing experiments done in vitro in tumor models and in vivo in mouse models in which the tumor was induced by means of radiation or chemical exposure, expressing oncogenes or deleting tumor suppression genes. We also discuss the proposed mechanisms of CR anti-tumor action. Lastly, we argue the necessity of gene expression studies in cancerous versus normal cells upon CR.\",\n \"title\": \"Insights into the beneficial effect of caloric/ dietary restriction for a healthy and prolonged life\"\n },\n {\n \"docid\": \"MED-3141\",\n \"text\": \"OBJECTIVE: To evaluate the associations with chronic disease risk and mortality of the consequences of bean-free diets in Taiwanese adults with regard to gender. DESIGN: A sub-sample of the National Health Interview Survey (NHIS) in 2001 agreed to physical examination in the subsequent year. This group then took part in the Taiwanese Survey of Hyperglycaemia, Hyperlipidaemia and Hypertension (TwSHHH) in 2002. SETTING: Individual records were linked to the eventual death files from 2002 to 2008. SUBJECTS: Up to the end of 2008, a total of 2820 men and 2950 women were tracked by death registry over the 6·8 years of follow-up. RESULTS: Among 38,077 person-years, an average follow-up 6·5 years, 225 all-cause deaths were identified. Generalized linear models showed beans to be favourable for metabolic syndrome (other than for fasting glucose) in men; in women, beans were favourable for waist circumference and HbA1c. Cumulative logistic regression models for the effect of a bean-free diet on metabolic syndrome scores according to the Taiwanese-modified National Cholesterol Education Program-Adult Treatment Panel III (NCEP-tw) gave adjusted odds ratios of 1·83 in men and 1·45 in women. Cox regression models for the bean-free diet showed an increased hazard ratio for all-cause mortality among women (1·98, 95% CI 1·03, 3·81) but not men (1·28, 95% CI 0·76, 2·16). CONCLUSIONS: A bean-free diet may play a role in developing the metabolic syndrome in both genders, and is a significant predictor of all-cause mortality in Taiwanese women but not men.\",\n \"title\": \"A bean-free diet increases the risk of all-cause mortality among Taiwanese women: the role of the metabolic syndrome.\"\n },\n {\n \"docid\": \"MED-3281\",\n \"text\": \"INTRODUCTION: Amino acid auxotrophy or the metabolic defect which renders cancer incapable of surviving under amino acid depleted conditions is being exploited and explored as a therapeutic against cancer. Early clinical data on asparagine- and arginine-depleting drugs have demonstrated low toxicity and efficacy in melanoma, hepatocellular carcinoma and acute lymphoblastic leukemia. Methionine auxotrophy is a novel niche currently under exploration for targeting certain cancers. AREAS COVERED: In this review we explore the discovery of methionine auxotrophy followed by in vitro, in vivo and patient data on targeting cancer with methionine depletion. We end with a small discussion on bioengineering, pegylation and red blood cell encapsulation as mechanisms for decreasing immunogenicity of methionine-depleting drugs. We hope to provide a platform for future pharmacology, toxicology and cytotoxicity studies with methionine depletion therapy and drugs. EXPERT OPINION: Although methionine auxotrophy seems as a viable target, extensive research addressing normal versus cancer cell toxicity needs to be conducted. Further research also needs to be conducted into the molecular mechanism associated with methionine depletion therapy. Finally, novel methods need to be developed to decrease the immunogenicity of methionine-depleting drugs, a current issue with protein therapeutics.\",\n \"title\": \"Targeting methionine auxotrophy in cancer: discovery & exploration.\"\n },\n {\n \"docid\": \"MED-3874\",\n \"text\": \"Background Prostate cancer affects one-out-of-six men during their lifetime. Dietary factors are postulated to influence the development and progression of prostate cancer. Low-fat diets and flaxseed supplementation may offer potentially protective strategies. Methods We undertook a multi-site, randomized controlled trial to test the effects of low-fat and/or flaxseed-supplemented diets on the biology of the prostate and other biomarkers. Prostate cancer patients (n=161) scheduled at least 21 days before prostatectomy were randomly assigned to one of the following arms: 1) control (usual diet); 2) flaxseed-supplemented diet (30 g/day); 2) low-fat diet (<20% total energy); or 4) flaxseed-supplemented, low-fat diet. Blood was drawn at baseline and prior to surgery and analyzed for prostate specific antigen (PSA), sex hormone binding globulin, testosterone, insulin-like growth factor-1 and binding protein-3, c-reactive protein, and total and low density lipoprotein cholesterol. Tumors were assessed for proliferation (Ki-67, the primary endpoint) and apoptosis. Results Men were on protocol an average of 30 days. Proliferation rates were significantly lower (P < 0.002) among men assigned to the flaxseed arms. Median Ki-67 positive cells/total nuclei ratios (x100) were 1.66 (flaxseed-supplemented diet) and 1.50 (flaxseed-supplemented, low-fat diet) vs. 3.23 (control) and 2.56 (low-fat diet). No differences were observed between arms with regard to side effects, apoptosis, and most serological endpoints; however, men on low-fat diets experienced significant decreases in serum cholesterol (P=0.048). Conclusions Findings suggest that flaxseed is safe, and associated with biologic alterations that may be protective for prostate cancer. Data also further support low-fat diets to manage serum cholesterol.\",\n \"title\": \"Flaxseed Supplementation (not Dietary Fat Restriction) Reduces Prostate Cancer Proliferation Rates in Men Presurgery\"\n },\n {\n \"docid\": \"MED-4050\",\n \"text\": \"Green tea is a commonly consumed beverage in Asia and has been suggested to have anti-inflammatory and possible anti-carcinogenic properties in laboratory studies. We sought to examine the association between green tea consumption and risk of breast cancer incidence or recurrence, using all available epidemiologic evidence to date. We conducted a systematic search of five databases and performed a meta-analysis of studies of breast cancer risk and recurrence published between 1998 and 2009, encompassing 5,617 cases of breast cancer. Summary relative risks (RR) were calculated using a fixed effects model, and tests of heterogeneity across combined studies were conducted. We identified two studies of breast cancer recurrence and seven studies of breast cancer incidence. Increased green tea consumption (more than three cups a day) was inversely associated with breast cancer recurrence (Pooled RR = 0.73, 95% CI: 0.56-0.96). An analysis of case-control studies of breast cancer incidence suggested an inverse association with a pooled RR of 0.81 (95% CI: 0.75, 0.88) while no association was found among cohort studies of breast cancer incidence. Combining all studies of breast cancer incidence resulted in significant heterogeneity. Available epidemiologic evidence supports the hypothesis that increased green tea consumption may be inversely associated with risk of breast cancer recurrence. The association between green tea consumption and breast cancer incidence remains unclear based on the current evidence.\",\n \"title\": \"Green tea consumption and breast cancer risk or recurrence: a meta-analysis.\"\n },\n {\n \"docid\": \"MED-3197\",\n \"text\": \"Background: A Step I diet with lean beef compared with lean white meat both decrease LDL cholesterol. To our knowledge, no studies have evaluated a low–saturated fatty acid (SFA) (<7% calories) diet that contains lean beef. Objective: We studied the effect on LDL cholesterol of cholesterol-lowering diets with varying amounts of lean beef [ie, Dietary Approaches to Stop Hypertension (DASH): 28 g beef/d; Beef in an Optimal Lean Diet (BOLD): 113 g beef/d; and Beef in an Optimal Lean Diet plus additional protein (BOLD+): 153 g beef/d] compared with that of a healthy American diet (HAD). Design: Thirty-six hypercholesterolemic participants (with LDL-cholesterol concentrations >2.8 mmol/L) were randomly assigned to consume each of the 4 diets (HAD: 33% total fat, 12% SFA, 17% protein, and 20 g beef/d), DASH (27% total fat, 6% SFA, 18% protein, and 28 g beef/d), BOLD (28% total fat, 6% SFA, 19% protein, and 113 g beef/d), and BOLD+ (28% total fat, 6% SFA, 27% protein, and 153 g beef/d) for 5 wk. Results: There was a decrease in total cholesterol (TC) and LDL-cholesterol concentrations (P < 0.05) after consumption of the DASH (−0.49 ± 0.11 and −0.37 ± 0.09 mmol/L, respectively), BOLD (−0.48 ± 0.10 and −0.35 ± 0.9 mmol/L, respectively), and BOLD+ (−0.50 ± 0.10 and −0.345 ± 0.09 mmol/L, respectively) diets compared with after consumption of the HAD (−0.22 ± 0.10 and −0.14 ± 0.10 mmol/L, respectively). Apolipoprotein A-I, C-III, and C-III bound to apolipoprotein A1 particles decreased after BOLD and BOLD+ diets compared with after the HAD, and there was a greater decrease in apolipoprotein B after consumption of the BOLD+ diet than after consumption of the HAD (P < 0.05 for both). LDL cholesterol and TC decreased after consumption of the DASH, BOLD, and BOLD+ diets when the baseline C-reactive protein (CRP) concentration was <1 mg/L; LDL cholesterol and TC decreased when baseline CRP concentration was >1 mg/L with the BOLD and BOLD+ diets. Conclusions: Low-SFA, heart-healthy dietary patterns that contain lean beef elicit favorable effects on cardiovascular disease (CVD) lipid and lipoprotein risk factors that are comparable to those elicited by a DASH dietary pattern. These results, in conjunction with the beneficial effects on apolipoprotein CVD risk factors after consumption of the BOLD and BOLD+ diets, which were greater with the BOLD+ diet, provide support for including lean beef in a heart-healthy dietary pattern. This trial was registered at clinicaltrials.gov as NCT00937898.\",\n \"title\": \"Beef in an Optimal Lean Diet study: effects on lipids, lipoproteins, and apolipoproteins\"\n },\n {\n \"docid\": \"MED-1721\",\n \"text\": \"Objective To examine the relation between body mass index (kg/m2) and cancer incidence and mortality. Design Prospective cohort study. Participants 1.2 million UK women recruited into the Million Women Study, aged 50-64 during 1996-2001, and followed up, on average, for 5.4 years for cancer incidence and 7.0 years for cancer mortality. Main outcome measures Relative risks of incidence and mortality for all cancers, and for 17 specific types of cancer, according to body mass index, adjusted for age, geographical region, socioeconomic status, age at first birth, parity, smoking status, alcohol intake, physical activity, years since menopause, and use of hormone replacement therapy. Results 45 037 incident cancers and 17 203 deaths from cancer occurred over the follow-up period. Increasing body mass index was associated with an increased incidence of endometrial cancer (trend in relative risk per 10 units=2.89, 95% confidence interval 2.62 to 3.18), adenocarcinoma of the oesophagus (2.38, 1.59 to 3.56), kidney cancer (1.53, 1.27 to 1.84), leukaemia (1.50, 1.23 to 1.83), multiple myeloma (1.31, 1.04 to 1.65), pancreatic cancer (1.24, 1.03 to 1.48), non-Hodgkin's lymphoma (1.17, 1.03 to 1.34), ovarian cancer (1.14, 1.03 to 1.27), all cancers combined (1.12, 1.09 to 1.14), breast cancer in postmenopausal women (1.40, 1.31 to 1.49) and colorectal cancer in premenopausal women (1.61, 1.05 to 2.48). In general, the relation between body mass index and mortality was similar to that for incidence. For colorectal cancer, malignant melanoma, breast cancer, and endometrial cancer, the effect of body mass index on risk differed significantly according to menopausal status. Conclusions Increasing body mass index is associated with a significant increase in the risk of cancer for 10 out of 17 specific types examined. Among postmenopausal women in the UK, 5% of all cancers (about 6000 annually) are attributable to being overweight or obese. For endometrial cancer and adenocarcinoma of the oesophagus, body mass index represents a major modifiable risk factor; about half of all cases in postmenopausal women are attributable to overweight or obesity.\",\n \"title\": \"Cancer incidence and mortality in relation to body mass index in the Million Women Study: cohort study\"\n },\n {\n \"docid\": \"MED-1724\",\n \"text\": \"A considerable amount of evidence is consistent with the proposition that systemic IGF-I activity acts as pacesetter in the aging process. A reduction in IGF-I activity is the common characteristic of rodents whose maximal lifespan has been increased by a wide range of genetic or dietary measures, including caloric restriction. The lifespans of breeds of dogs and strains of rats tend to be inversely proportional to their mature weight and IGF-I levels. The link between IGF-I and aging appears to be evolutionarily conserved; in worms and flies, lifespan is increased by reduction-of-function mutations in signaling intermediates homologous to those which mediate insulin/IGF-I activity in mammals. The fact that an increase in IGF-I activity plays a key role in the induction of sexual maturity, is consistent with a broader role for-IGF-I in aging regulation. If down-regulation of IGF-I activity could indeed slow aging in humans, a range of practical measures for achieving this may be at hand. These include a low-fat, whole-food, vegan diet, exercise training, soluble fiber, insulin sensitizers, appetite suppressants, and agents such as flax lignans, oral estrogen, or tamoxifen that decrease hepatic synthesis of IGF-I. Many of these measures would also be expected to decrease risk for common age-related diseases. Regimens combining several of these approaches might have a sufficient impact on IGF-I activity to achieve a useful retardation of the aging process. However, in light of the fact that IGF-I promotes endothelial production of nitric oxide and may be of especial importance to cerebrovascular health, additional measures for stroke prevention-most notably salt restriction-may be advisable when attempting to down-regulate IGF-I activity as a pro-longevity strategy.\",\n \"title\": \"A low-fat, whole-food vegan diet, as well as other strategies that down-regulate IGF-I activity, may slow the human aging process.\"\n },\n {\n \"docid\": \"MED-1711\",\n \"text\": \"Summary Objectives The insulin-like growth factor (IGF) signaling pathway has been implicated in the pathogenesis of numerous tumor types, including non-small cell lung cancer (NSCLC). Figitumumab is a fully human IgG2 monoclonal antibody against IGF-1 receptor (IGF-1R). Methods This phase I, open-label, dose-escalation study (ClinicalTrials.gov: NCT00603538) assessed the safety and tolerability of figitumumab (6, 10 and 20 mg/kg) in combination with carboplatin (area under the curve: 6 mg·min/mL) and paclitaxel (200 mg/m2) in Japanese patients (N = 19) with chemotherapy-naïve, advanced NSCLC. Treatments were administered intravenously on day 1 of a 21-day cycle for four to six cycles. Pharmacokinetics, biomarkers, and antitumor activity were also evaluated. Results Figitumumab in combination with carboplatin and paclitaxel was well tolerated at doses up to 20 mg/kg; no dose-limiting toxicities were observed at this dose level. When given in combination, figitumumab plasma exposure increased in an approximately dose-proportional manner. The approximate 2-fold accumulation following repeated administration supported the 21-day regimen as appropriate for figitumumab administration. Serum total IGF-1 and IGF binding protein-3 concentrations increased following figitumumab dosing, but a clear dose-dependent relationship was not demonstrated. Seven of 18 evaluable patients experienced a partial response. Conclusions Figitumumab 20 mg/kg in combination with carboplatin and paclitaxel was well tolerated in chemotherapy-naïve Japanese patients with NSCLC. Further analysis of biomarker data is necessary for the development of figitumumab therapy.\",\n \"title\": \"Figitumumab combined with carboplatin and paclitaxel in treatment-naïve Japanese patients with advanced non-small cell lung cancer\"\n },\n {\n \"docid\": \"MED-1258\",\n \"text\": \"Reductions in low-density lipoprotein-cholesterol (LDL-C) result from diets containing almonds, or diets that are either low in saturated fat or high in viscous fibers, soy proteins, or plant sterols. We have therefore combined all of these interventions in a single diet (portfolio diet) to determine whether cholesterol reductions could be achieved of similar magnitude to those reported in recent statin trials which reduced cardiovascular events. Twenty-five hyperlipidemic subjects consumed either a portfolio diet (n=13), very low in saturated fat and high in plant sterols (1.2 g/1,000 kcal), soy protein (16.2 g/1,000 kcal), viscous fibers (8.3 g/1,000 kcal), and almonds (16.6 g/1,000 kcal), or a low-saturated fat diet (n=12) based on whole-wheat cereals and low-fat dairy foods. Fasting blood, blood pressure, and body weight were obtained at weeks 0, 2, and 4 of each phase. LDL-C was reduced by 12.1% +/- 2.4% (P<.001) on the low-fat diet and by 35.0% +/- 3.1% (P<.001) on the portfolio diet, which also reduced the ratio of LDL-C to high-density lipoprotein-cholesterol (HDL-C) significantly (30.0% +/- 3.5%; P<.001). The reductions in LDL-C and the LDL:HDL-C ratio were both significantly lower on the portfolio diet than on the control diet (P<.001 and P<.001, respectively). Mean weight loss was similar on test and control diets (1.0 kg and 0.9 kg, respectively). No difference was seen in blood pressure, HDL-C, serum triglycerides, lipoprotein(a) [Lp(a)], or homocysteine concentrations between diets. Combining a number of foods and food components in a single dietary portfolio may lower LDL-C similarly to statins and so increase the potential effectiveness of dietary therapy.\",\n \"title\": \"The effect of combining plant sterols, soy protein, viscous fibers, and almonds in treating hypercholesterolemia.\"\n },\n {\n \"docid\": \"MED-3775\",\n \"text\": \"We investigated the beneficial effects of drinking supplementary water during the school day on the cognitive performance and transitory subjective states, such as fatigue or vigor, in 168 children aged between 9 and 11years who were living in a hot climate (South Italy, Sardinia). The classes were randomly divided into an intervention group, which received water supplementation, and a control group. Dehydration was determined by urine sampling and was defined as urine osmolality greater than 800mOsm/kg H(2)O (Katz, Massry, Agomn, & Toor, 1965). The change in the scores from the morning to the afternoon of hydration levels, cognitive performance and transitory subjective states were correlated. In line with a previous observational study that evaluated the hydration status of school children living in a country with a hot climate (Bar-David, Urkin, & Kozminsky, 2005), our results showed that a remarkable proportion of children were in a state of mild, voluntary dehydration at the beginning of the school day (84%). We found a significant negative correlation between dehydration and the auditory number span, which indicates a beneficial effect of drinking supplementary water at school on short-term memory. Moreover, there was a positive correlation between dehydration and performance in the verbal analogy task. The results are discussed in the light of the complexity of the neurobiological mechanisms involved in the relationship between hydration status and cognition. Copyright © 2012 Elsevier Ltd. All rights reserved.\",\n \"title\": \"Effects of drinking supplementary water at school on cognitive performance in children.\"\n },\n {\n \"docid\": \"MED-2445\",\n \"text\": \"Allergic disorders encompass skin, food and respiratory allergies. Sensitization to a normally harmless allergen results in the immune system being biased to a predominant T-helper type 2 response. Re-exposure to the same allergen leads to a robust secretion of allergy-related mediators that eventually triggers symptoms. Our understanding of these disorders has enabled the search of therapeutic approaches that can either modulate the sensitization process or impact on allergic mediators, thus helping manage allergic symptoms. Polyphenols are one such class of compounds that are found in foods and plant sources and have been investigated for their anti-allergic effect in different disease models and in human clinical trials. Their anti-inflammatory profile is known to impact on the recruitment of immune cells to the skin and in preventing the development of secondary infections following disruption of the skin barrier. The interaction of polyphenols with proteins can modulate the process of allergic sensitization and their direct effect on allergic effector cells such as mast cells inhibit mediator release, resulting in the alleviation of symptoms. In addition, their endogenous anti-oxidant ability limits the extent of cellular injury from free radicals during the allergic insult. Overall, polyphenols hold promise as anti-allergy agents capable of influencing multiple biological pathways and immune cell functions in the allergic immune response and deserve further investigation. The objective of the current review is to summarize the key findings and progress made in studying polyphenols as anti-allergic ingredients. Special emphasis is placed in this review to highlight key physiological, cellular and signalling pathways implicated in the mechanism of action of different polyphenols in the context of allergic disorders and their manifestations. © 2011 Blackwell Publishing Ltd.\",\n \"title\": \"Dietary polyphenols in the prevention and treatment of allergic diseases.\"\n },\n {\n \"docid\": \"MED-3278\",\n \"text\": \"Lung cancer (LC) continues to represent a heavy burden for health care systems worldwide. Epidemiological studies predict that its role will increase in the near future. While patient prognosis is strongly associated with tumour stage and early detection of disease, no screening test exists so far. It has been suggested that electronic sensor devices, commonly referred to as ‘electronic noses’, may be applicable to identify cancer-specific volatile organic compounds in the breath of patients and therefore may represent promising screening technologies. However, three decades of research did not bring forward a clinically applicable device. Here, we propose a new research approach by involving specially trained sniffer dogs into research strategies by making use of their ability to identify LC in the breath sample of patients.\",\n \"title\": \"Sniffer dogs as part of a bimodal bionic research approach to develop a lung cancer screening\"\n },\n {\n \"docid\": \"MED-3958\",\n \"text\": \"Flanders is densely populated with much industry and intensive farming. Sexual maturation of adolescents (aged 14-15 years) was studied in relation to internal exposure to pollutants. Serum levels of pollutants and sex hormones were measured in 1679 participants selected as a random sample of the adolescents residing in the study areas. Data on sexual development were obtained from the medical school examination files. Self-assessment questionnaires provided information on health, use of medication and lifestyle factors. In boys, serum levels of hexachlorobenzene (HCB), p,p'-DDE and polychlorinated biphenyls (sum of marker PCB138, 153 and 180) were significantly and positively associated with pubertal staging (pubic hair and genital development). Higher levels of serum HCB and blood lead were associated with, respectively, a lower and a higher risk of gynecomastia. In girls, significant and negative associations were detected between blood lead and pubic hair development; higher exposure to PCBs was significantly associated with a delay in timing of menarche. Environmental exposures to pollutants at levels actually present in the Flemish population are associated with measurable effects on pubertal development. However, further understanding of toxic mode of action and sensitive windows of exposure is needed to explain the current findings.\",\n \"title\": \"Internal exposure to pollutants and sexual maturation in Flemish adolescents.\"\n },\n {\n \"docid\": \"MED-3451\",\n \"text\": \"Oxidative stress is a natural physiological process that describes an imbalance between free radical production and the ability of the antioxidant defence system of the body to neutralize free radicals. Free radicals can be beneficial as they may promote wound healing and contribute to a healthy immune response. However, free radicals can have a detrimental impact when they interfere with the regulation of apoptosis and thus play a role in the promotion of some cancers and conditions such as cardiovascular disease. Antioxidants are molecules that reduce the damage associated with oxidative stress by counteracting free radicals. Regular exercise is a vital component of a healthy lifestyle, although it can increase oxidative stress. As a typical vegetarian diet comprises a wide range of antioxidant-rich foods, it is plausible that the consumption of these foods will result in an enhanced antioxidant system capable of reducing exercise-induced oxidative stress. In addition, a relationship between a vegetarian diet and lower risks of cardiovascular disease and some cancers has been established. This review explores the current available evidence linking exercise, vegetarians, antioxidants, and oxidative stress.\",\n \"title\": \"Could a vegetarian diet reduce exercise-induced oxidative stress? A review of the literature.\"\n },\n {\n \"docid\": \"MED-3954\",\n \"text\": \"BACKGROUND: A male epidemic of ischaemic heart disease (IHD) emerges with economic development. It has previously been hypothesised that this epidemic is due to nutritionally driven levels of pubertal sex steroids, which lead to a more atherogenic body shape and lipid profile in boys but not girls, without any sex-specific effects on glucose metabolism. This study tests this hypothesis by examining the association of childhood meat eating with IHD risk in a developing Chinese population. METHODS: Multivariable linear and censored regression was used in a cross-sectional study of 19,418 Chinese older (≥ 50 years) men and women from the Guangzhou Biobank Cohort Study (phases 2 and 3) to assess the adjusted associations of childhood meat eating with waist to hip ratio (WHR), high-density lipoprotein cholesterol and fasting plasma glucose. RESULTS: Adjusted for age, childhood hunger, life-course socioeconomic position and current lifestyle childhood almost daily meat eating compared with less than weekly meat eating was associated with higher WHR (0.007, 95% CI 0.0003 to 0.01) in men but not women. No association with fasting glucose was observed. CONCLUSIONS: Given the potential limitations of this study, especially the crude nature of the exposure and modest findings, the results should be considered as preliminary. However, they do lend support to the hypothesis that the male epidemic of premature IHD and sexual divergence in IHD rates that occur with economic development may be nutritionally driven in childhood. In elucidating the developmental origins of non-communicable chronic diseases, more attention should be focused on the sociohistorical context and the role of puberty.\",\n \"title\": \"Does childhood meat eating contribute to sex differences in risk factors for ischaemic heart disease in a developing population?\"\n },\n {\n \"docid\": \"MED-2361\",\n \"text\": \"The most common clinical manifestation of Lyme disease is the characteristic rash, erythema migrans (EM). In the 1980s EM-like eruptions were reported in Missouri and other southeastern states. The EM-like eruptions, which were of unknown etiology, often followed the bite of the Lone Star tick (Amblyomma americanum) and the rash is called STARI (southern tick-associated rash illness). Although the Lone Star tick is found in the Lyme disease-endemic areas of New England and Mid-Atlantic regions of the United States, STARI has been reported only once from the Northeast and Mid-Atlantic regions. We report a child from Connecticut who visited Long Island, New York, and developed a rash that was thought to be EM. Because the patient failed to respond to antibiotics used to treat Lyme disease, an investigation ensued, and the diagnosis of STARI was established.\",\n \"title\": \"Southern Tick-Associated Rash Illness (STARI) in the North: STARI following a tick bite in Long Island, New York.\"\n },\n {\n \"docid\": \"MED-3776\",\n \"text\": \"Little research has examined the effect of water consumption on cognition in children. We examined whether drinking water improves performance from baseline to test in twenty-three 6-7-year-old children. There were significant interactions between time of test and water group (water/no water), with improvements in the water group on thirst and happiness ratings, visual attention and visual search, but not visual memory or visuomotor performance. These results indicate that even under conditions of mild dehydration, not as a result of exercise, intentional water deprivation or heat exposure, children's cognitive performance can be improved by having a drink of water.\",\n \"title\": \"Does having a drink help you think? 6-7-Year-old children show improvements in cognitive performance from baseline to test after having a drink of ...\"\n },\n {\n \"docid\": \"MED-4897\",\n \"text\": \"Consumption of cow's milk and cow's milk protein result in changes of the hormonal axis of insulin, growth hormone and insulin-like growth factor-1(IGF-1) in humans. Milk consumption raises IGF-1 serum levels in the perinatal period, adolescence and adulthood. During puberty with the physiological onset of increased secretion of growth hormone, IGF-1 serum levels increase and are further enhanced by milk consumption. IGF-1 is a potent mitogen; after binding to its receptor in various tissues, it induces cell proliferation and inhibits apoptosis. Keratinocytes and sebocytes, as well as the androgen-synthesizing adrenals and gonads, are stimulated by IGF-1. The epidemic incidence of adolescent acne in Western milk-consuming societies can be explained by the increased insulin- and IGF-1-stimulation of sebaceous glands mediated by milk consumption. Acne can be regarded as a model for chronic Western diseases with pathologically increased IGF-1-stimulation. Many other organs, such as the thymus, bones, all glands, and vascular smooth muscle cells as well as neurons are subject to this abnormally increased hormonal stimulation. The milk-induced change of the IGF-1-axis most likely contributes to the development of fetal macrosomia, induction of atopy, accelerated linear growth, atherosclerosis, carcinogenesis and neurodegenerative diseases. Observations of molecular biology are supported by epidemiologic data and unmask milk consumption as a promoter of chronic diseases of Western societies.\",\n \"title\": \"Milk consumption: aggravating factor of acne and promoter of chronic diseases of Western societies.\"\n },\n {\n \"docid\": \"MED-2826\",\n \"text\": \"Background Curcumin extracts of turmeric are proposed to produce health benefits. To date, human intervention studies have focused mainly on people with existing health problems given high doses of poorly absorbed curcumin. The purpose of the current study was to check whether in healthy people, a low dose of a lipidated curcumin extract could alter wellness-related measures. Methods The present study was conducted in healthy middle aged people (40–60 years old) with a low dose of curcumin (80 mg/day) in a lipidated form expected to have good absorption. Subjects were given either curcumin (N = 19) or placebo (N = 19) for 4 wk. Blood and saliva samples were taken before and after the 4 weeks and analyzed for a variety of blood and saliva measures relevant to health promotion. Results Curcumin, but not placebo, produced the following statistically significant changes: lowering of plasma triglyceride values, lowering of salivary amylase levels, raising of salivary radical scavenging capacities, raising of plasma catalase activities, lowering of plasma beta amyloid protein concentrations, lowering of plasma sICAM readings, increased plasma myeloperoxidase without increased c-reactive protein levels, increased plasma nitric oxide, and decreased plasma alanine amino transferase activities. Conclusion Collectively, these results demonstrate that a low dose of a curcumin-lipid preparation can produce a variety of potentially health promoting effects in healthy middle aged people.\",\n \"title\": \"Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people\"\n },\n {\n \"docid\": \"MED-2655\",\n \"text\": \"Background Broad dietary patterns have been linked to asthma but the relative contribution of specific nutrients is unclear. Soy genistein has important anti-inflammatory and other biological effects that might be beneficial in asthma. A positive association was previously reported between soy genistein intake and lung function but not with asthma exacerbations. Aims To conduct a post-hoc analysis of patients with inadequately controlled asthma enrolled in a prospective multicentre clinical trial to replicate this association. Methods A total of 300 study participants were included in the analysis. Dietary soy genistein intake was measured using the Block Soy Foods Screener. The level of soy genistein intake (little or no intake, moderate intake, or high intake) was compared with baseline lung function (pre-bronchodilator forced expiratory volume in 1 second (FEV1)) and asthma control (proportion of participants with an episode of poor asthma control (EPAC) and annualised rates of EPACs over a 6-month follow-up period. Results Participants with little or no genistein intake had a lower baseline FEV1 than those with a moderate or high intake (2.26L vs. 2.53L and 2.47L, respectively; p=0.01). EPACs were more common among those with no genistein intake than in those with a moderate or high intake (54% vs. 35% vs. 40%, respectively; p<0.001). These findings remained significant after adjustment for patient demographics and body mass index. Conclusions In patients with asthma, consumption of a diet with moderate to high amounts of soy genistein is associated with better lung function and better asthma control.\",\n \"title\": \"Association of dietary soy genistein intake with lung function and asthma control: a post-hoc analysis of patients enrolled in a prospective multicentre clinical trial\"\n },\n {\n \"docid\": \"MED-3458\",\n \"text\": \"The single cell gel electrophoresis (SCG) assay (comet assay) is a sensitive technique for detecting the presence of DNA strand-breaks and alkali-labile damage in individual cells. This technique was used to study peripheral blood cells from three volunteers after physical activity. The test subjects had to run on a treadmill and were checked for blood pressure and ECG, lactate concentration and creatine kinase activity. Blood was taken before and several times during and after the run. In a first multiple step test, the volunteers ran as long as possible with increasing speed. In a second test they had to run for 45 min with a fixed individual speed which was defined to ensure an aerobic metabolism. In the first test, the white blood cells of all subjects showed increased DNA migration in the SCG assay. The effect was seen 6 h after the end of the exercise and reached its maximum 24 h later. After 72 h, DNA migration decreased to about control level. The distribution of DNA migration among cells clearly demonstrated that the majority of white blood cells exhibited increased DNA migration and that the effect was not only due to a small fraction of damaged cells. From the same blood samples, blood cultures were set up to study a possible effect on the frequency of sister chromatid exchanges (SCE), another indicator for genotoxic effects. However, there was no significant increase in SCE in any of the cultures. In the second exercise, during aerobic metabolism, the effect on DNA migration was not seen.(ABSTRACT TRUNCATED AT 250 WORDS)\",\n \"title\": \"Does physical activity induce DNA damage?\"\n },\n {\n \"docid\": \"MED-2586\",\n \"text\": \"A systematic review and meta-analysis were carried out to study the effects of low-carbohydrate diet (LCD) on weight loss and cardiovascular risk factors (search performed on PubMed, Cochrane Central Register of Controlled Trials and Scopus databases). A total of 23 reports, corresponding to 17 clinical investigations, were identified as meeting the pre-specified criteria. Meta-analysis carried out on data obtained in 1,141 obese patients, showed the LCD to be associated with significant decreases in body weight (-7.04 kg [95% CI -7.20/-6.88]), body mass index (-2.09 kg m(-2) [95% CI -2.15/-2.04]), abdominal circumference (-5.74 cm [95% CI -6.07/-5.41]), systolic blood pressure (-4.81 mm Hg [95% CI -5.33/-4.29]), diastolic blood pressure (-3.10 mm Hg [95% CI -3.45/-2.74]), plasma triglycerides (-29.71 mg dL(-1) [95% CI -31.99/-27.44]), fasting plasma glucose (-1.05 mg dL(-1) [95% CI -1.67/-0.44]), glycated haemoglobin (-0.21% [95% CI -0.24/-0.18]), plasma insulin (-2.24 micro IU mL(-1) [95% CI -2.65/-1.82]) and plasma C-reactive protein, as well as an increase in high-density lipoprotein cholesterol (1.73 mg dL(-1) [95%CI 1.44/2.01]). Low-density lipoprotein cholesterol and creatinine did not change significantly, whereas limited data exist concerning plasma uric acid. LCD was shown to have favourable effects on body weight and major cardiovascular risk factors; however the effects on long-term health are unknown. © 2012 The Authors. obesity reviews © 2012 International Association for the Study of Obesity.\",\n \"title\": \"Systematic review and meta-analysis of clinical trials of the effects of low carbohydrate diets on cardiovascular risk factors.\"\n },\n {\n \"docid\": \"MED-4058\",\n \"text\": \"A facile method was established to measure heterocyclic aromatic amines (HAAs) accumulated in human hair and rodent fur. The samples were digested by base hydrolysis, and the liberated HAAs were isolated by tandem solvent/solid-phase extraction. Quantification was done by liquid chromatography/tandem mass spectrometry, using a triple stage quadrupole mass spectrometer in the selected reaction monitoring mode. In a pilot study of 12 human volunteers, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was detected in hair of six meat-eaters at levels ranging from 290 to 890 pg/g hair. 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-9H-pyrido[2,3-b]indole (AαC) were below the limit of quantification (LOQ) (50 pg/g hair) in hair from meat-eaters and six vegetarians. PhIP was detected in the hair from one vegetarian, and at level just above the LOQ (65 pg/g hair), indicating PhIP exposure occurs primarily through meat consumption. The levels of PhIP in hair samples from two meat-eaters varied by less than 24% over a 6-month interval, signifying that the exposure to PhIP and its accumulation in hair are relatively constant over time. In a controlled feeding study, female C57BL/6 mice were given these HAAs in their drinking water for 1 month, at six daily dose concentrations ranging from 0, 0.080 to 800 µg/kg body weight. PhIP was detected in fur of mice at all doses, whereas AαC and MeIQx were detected in fur at dosages ≥0.8 µg AαC/kg body weight and ≥8 µg MeIQx/kg body weight. There was a strong positive relationship between dosage and each of the HAAs accumulated in fur and their DNA adducts formed in liver and colon (p-values <0.0001); however, the levels of HAA in fur did not correlate to the levels of DNA adducts after adjustment of dose. Thus, hair appears to be a promising long-lived biomarker with by which we can assess the exposure to PhIP, a potential human carcinogen.\",\n \"title\": \"Biomonitoring of Carcinogenic Heterocyclic Aromatic Amines in Hair: A Validation Study\"\n },\n {\n \"docid\": \"MED-2293\",\n \"text\": \"The CODEX Alimentarius definition of dietary fiber includes all nondigestible carbohydrate polymers with a degree of polymerization of 3 or more as dietary fiber with the proviso that they show health benefits. The global definition, if accepted by all authoritative bodies, offers a chance for international harmonization in research, food composition tables, and food labeling. Its nonacceptance highlights problems that may develop when definitions vary by region. The definition requires that the research community agrees upon physiological effects for which there is substantial scientific agreement, e.g., fibers’ effects on laxation and gut health, on attenuating blood lipids and blood glucose and insulin, and in promoting fermentation in the large bowel. The definition also necessitates the delineation of research protocols to prove the benefits of various isolated and synthesized fibers. These should emanate from evidence-based reviews that fairly weigh epidemiological data while considering that added fibers are not reflected in many food composition databases. They then should include well-controlled, randomized, control trials and utilize animal studies to determine mechanisms. Agreement on many study variables such as the type of subject and the type of baseline diet that best fits the question under investigation will also be needed. Finally, the definition establishes that all types of fiber can address the severe fiber consumption gap that exists throughout the world by recognizing that the combination of fiber-rich and -fortified foods increases fiber intake while allowing consumers to stay within allowed energy levels.\",\n \"title\": \"Dietary Fiber Future Directions: Integrating New Definitions and Findings to Inform Nutrition Research and Communication\"\n },\n {\n \"docid\": \"MED-3959\",\n \"text\": \"Context: Earlier age at menarche is associated with rapid infancy weight gain and childhood obesity. The role of hormone levels in mediating these associations is unclear. Objective: The aim of this study was to identify childhood hormone levels at age 8 yr that are associated with early menarche, independent of body size. Design, Settings, and Subjects: A total of 329 girls from a prospective United Kingdom birth cohort study provided blood samples at mean age 8.1 yr (range, 8.0–8.5) for hormone measurements and were followed longitudinally to establish age at menarche. Main Outcome Measures: Fasting plasma levels of IGF-I, androstenedione, dehydroepiandrosterone sulfate (DHEAS), leptin, insulin, IGF binding protein-1, and SHBG were measured. Age at menarche was reported by questionnaire and categorized as before 12.0, 12.0–13.0, or later than 13 yr. Results: Earlier menarche was associated with greater body weight, height, and body mass index at age 8 yr (all P-trend <0.001). Before adjustment for body size, earlier menarche was associated with higher levels of IGF-I, androstenedione, DHEAS, leptin, and fasting insulin, and with lower levels of IGF binding protein-1 and SHBG at age 8 yr (all P < 0.01). After adjustment for body mass index and height at age 8 yr, only IGF-I (P = 0.004), androstenedione (P = 0.01), and DHEAS (P = 0.01) remained associated with earlier menarche. Conclusions: Associations between higher levels of IGF-I and adrenal androgens at age 8 yr with earlier menarche, independent of body size, support functional roles of these hormones in regulating puberty timing in girls. Higher levels of these hormones reported in children who exhibited rapid weight gain during infancy may indicate their role in developmental pathways leading to earlier sexual maturation.\",\n \"title\": \"Higher Levels of IGF-I and Adrenal Androgens at Age 8 Years Are Associated with Earlier Age at Menarche in Girls\"\n },\n {\n \"docid\": \"MED-2273\",\n \"text\": \"Objective To examine and quantify the relation between purine intake and the risk of recurrent gout attacks among gout patients. Methods The authors conducted a case-crossover study to examine associations of a set of putative risk factors with recurrent gout attacks. Individuals with gout were prospectively recruited and followed online for 1 year. Participants were asked about the following information when experiencing a gout attack: the onset date of the gout attack, clinical symptoms and signs, medications (including antigout medications), and presence of potential risk factors (including daily intake of various purine-containing food items) during the 2-day period prior to the gout attack. The same exposure information was also assessed over 2-day control periods. Results This study included 633 participants with gout. Compared with the lowest quintile of total purine intake over a 2-day period, OR of recurrent gout attacks were 1.17, 1.38, 2.21 and 4.76, respectively, with each increasing quintile (p for trend <0.001). The corresponding OR were 1.42, 1.34, 1.77 and 2.41 for increasing quintiles of purine intake from animal sources (p for trend <0.001), and 1.12, 0.99, 1.32 and 1.39 from plant sources (p=0.04), respectively. The effect of purine intake persisted across subgroups by sex, use of alcohol, diuretics, allopurinol, NSAIDs and colchicine. Conclusions The study findings suggest that acute purine intake increases the risk of recurrent gout attacks by almost fivefold among gout patients. Avoiding or reducing amount of purine-rich foods intake, especially of animal origin, may help reduce the risk of gout attacks.\",\n \"title\": \"Purine-rich foods intake and recurrent gout attacks\"\n },\n {\n \"docid\": \"MED-3781\",\n \"text\": \"In this study, a panel of normal human prostate cells (HPCs) and tumor cells derived from metastases were studied by (1)H NMR spectroscopy to determine whether the malignant transformation of HPCs results in the elevation of choline compounds. Although an elevated choline signal has been observed previously in clinical studies, the contribution of the different Cho compounds to this elevation, as well as their quantification, has not been established until now. Here we have shown that HPCs derived from metastases exhibit significantly higher phosphocholine as well as glycerophosphocholine levels compared with normal prostate epithelial and stromal cells. Thus the elevation of the choline peak observed clinically in prostate cancer is attributable to an alteration of phospholipid metabolism and not simply to increased cell density, doubling time, or other nonspecific effects. Androgen deprivation of the androgen receptor-positive cell lines resulted in a significant increase of choline compounds after chronic androgen deprivation of the LNCaP cell line and in a decrease of choline compounds after a more acute androgen deprivation of the LAPC-4 cell line. These data strongly support the use of proton magnetic resonance spectroscopic imaging to detect the presence of prostate cancer for diagnosis, to detect response subsequent to androgen ablation therapy, and to detect recurrence.\",\n \"title\": \"Detection of increased choline compounds with proton nuclear magnetic resonance spectroscopy subsequent to malignant transformation of human prosta...\"\n },\n {\n \"docid\": \"MED-2363\",\n \"text\": \"We have previously shown that an antibody pool present in normal human serum binds cytokine receptors in vitro and may therefore interfere with assays that capture cytokines using their receptors. Here we show that this antibody pool is the same as the natural antibody termed anti-gal, that binds to the alpha-galactosyl carbohydrate epitope (alpha-gal) and which is the predominant obstacle to xenotransplantation. We report that there are high levels of IgD anti alpha-gal in most volunteers, in addition to the IgG2, IgA and IgM immunoglobulin isotypes against alpha-gal previously described. To determine if anti-gal may interfere with assays that depend on capture of cytokine with its receptor, we measured levels of several anti-carbohydrate antibodies in a cohort of patients with advanced atherosclerosis that had previously been used to measure levels of active TGF-beta using such an assay. For many isotype / carbohydrate combinations, there is a large and significant difference between the levels of anti-carbohydrate antibodies in patients with atherosclerosis and controls, after adjustment for age, sex and blood group. These results are similar to the previous data obtained for active TGF-beta, and therefore we cannot discount the possibility that anti-gal contributed to the previous data. Following further adjustment for several risk factors associated with cardiovascular disease, several anti-carbohydrate antibodies were still significantly different between patients and controls. Therefore, anti-carbohydrate antibodies may represent a new class of risk factors that may be associated with presence of advanced atherosclerosis, although larger studies will be required to confirm this hypothesis.\",\n \"title\": \"A pattern of anti-carbohydrate antibody responses present in patients with advanced atherosclerosis.\"\n },\n {\n \"docid\": \"MED-1609\",\n \"text\": \"To examine extra-alimentary effects of high-carbohydrate, high-fiber (HCF) diets, insulin-mediated glucose disposal employing the euglycemic clamp and hepatic glucose output (HGO) employing [6,6-2H2]glucose were measured in 12 healthy young and old individuals before and after 21-28 d of an HCF diet. Diet lowered fasting concentrations of glucose from 5.3 +/- 0.2 to 5.1 +/- 0.1 mmol/L (p less than 0.01) and insulin from 66.0 +/- 7.9 to 49.5 +/- 5.7 pmol/L (p less than 0.01). Fasting serum cholesterol decreased from 5.17 +/- 0.18 to 3.80 +/- 0.20 mmol/L (p less than 0.01) in young individuals and from 6.15 +/- 0.52 to 4.99 +/- 0.49 mmol/L (p less than 0.01) in elderly individuals. Fasting serum triglyceride concentrations, basal HGO, and insulin suppression of HGO were unchanged by the diet. Glucose disposal rates increased from 18.87 +/- 1.66 before 23.87 +/- 2.78 mumol.kg-1.min-1 after the diet (p less than 0.02). Therefore, HCF diets may improve carbohydrate economy by enhanced peripheral sensitivity to insulin.\",\n \"title\": \"High-carbohydrate, high-fiber diets increase peripheral insulin sensitivity in healthy young and old adults.\"\n },\n {\n \"docid\": \"MED-3927\",\n \"text\": \"Objective: Epidemiologic studies consistently link caffeine, a nonselective adenosine antagonist, to lower risk of Parkinson disease (PD). However, the symptomatic effects of caffeine in PD have not been adequately evaluated. Methods: We conducted a 6-week randomized controlled trial of caffeine in PD to assess effects upon daytime somnolence, motor severity, and other nonmotor features. Patients with PD with daytime somnolence (Epworth >10) were given caffeine 100 mg twice daily ×3 weeks, then 200 mg twice daily ×3 weeks, or matching placebo. The primary outcome was the Epworth Sleepiness Scale score. Secondary outcomes included motor severity, sleep markers, fatigue, depression, and quality of life. Effects of caffeine were analyzed with Bayesian hierarchical models, adjusting for study site, baseline scores, age, and sex. Results: Of 61 patients, 31 were randomized to placebo and 30 to caffeine. On the primary intention-to-treat analysis, caffeine resulted in a nonsignificant reduction in Epworth Sleepiness Scale score (−1.71 points; 95% confidence interval [CI] −3.57, 0.13). However, somnolence improved on the Clinical Global Impression of Change (+0.64; 0.16, 1.13, intention-to-treat), with significant reduction in Epworth Sleepiness Scale score on per-protocol analysis (−1.97; −3.87, −0.05). Caffeine reduced the total Unified Parkinson's Disease Rating Scale score (−4.69 points; −7.7, −1.6) and the objective motor component (−3.15 points; −5.50, −0.83). Other than modest improvement in global health measures, there were no changes in quality of life, depression, or sleep quality. Adverse events were comparable in caffeine and placebo groups. Conclusions: Caffeine provided only equivocal borderline improvement in excessive somnolence in PD, but improved objective motor measures. These potential motor benefits suggest that a larger long-term trial of caffeine is warranted. Classification of evidence: This study provides Class I evidence that caffeine, up to 200 mg BID for 6 weeks, had no significant benefit on excessive daytime sleepiness in patients with PD.\",\n \"title\": \"Caffeine for treatment of Parkinson disease\"\n },\n {\n \"docid\": \"MED-4308\",\n \"text\": \"We examined the occurrence and coincidence of depressed mood and excessive carbohydrate intake in 19 patients who claimed to suffer from severe premenstrual syndrome and in nine control subjects, all as inpatients, during the early follicular and late luteal phases of their menstrual cycles. Mood was assessed with the Hamilton Depression Scale and an addendum that evaluated fatigue, sociability, appetite, and carbohydrate craving. Calorie and nutrient intakes were measured directly. The subjects with premenstrual syndrome significantly increased calorie intake during the late luteal phase (from 1892 +/- 104 to 2395 +/- 93 kcal, mean +/- SEM); carbohydrate intake increased by 24% from meals and by 43% from snacks. Protein intake failed to change, whereas intake of fat, a fixed constituent of all of the test foods, rose in proportion to calorie intake. The Hamilton Depression Scale and addendum scores rose from 2.0 +/- 0.5 to 21.2 +/- 0.8 (Hamilton Scale) and from 0.5 +/- 0.5 to 10.2 +/- 0.6 (addendum) among subjects with premenstrual syndrome during the luteal phase but failed to change among the controls (2.1 +/- 0.8 to 2.4 +/- 0.8, and 0.4 +/- 0.3 to 0.6 +/- 0.3). Consumption of a carbohydrate-rich, protein-poor evening test meal during the late luteal phase of the menstrual cycle improved depression, tension, anger, confusion, sadness, fatigue, alertness, and calmness scores (p less than 0.01) among patients with premenstrual syndrome. No effect of the meal was observed during the follicular phase or among the control subjects during either phase. Because synthesis of brain serotonin, which is known to be involved in mood and appetite, increases after carbohydrate intake, premenstrual syndrome subjects may overconsume carbohydrates in an attempt to improve their dysphoric mood state.\",\n \"title\": \"Effect of nutrient intake on premenstrual depression.\"\n },\n {\n \"docid\": \"MED-2510\",\n \"text\": \"Dietary restriction (DR) extends the lifespan of a wide range of species, although the universality of this effect has never been quantitatively examined. Here, we report the first comprehensive comparative meta-analysis of DR across studies and species. Overall, DR significantly increased lifespan, but this effect is modulated by several factors. In general, DR has less effect in extending lifespan in males and also in non-model organisms. Surprisingly, the proportion of protein intake was more important for life extension via DR than the degree of caloric restriction. Furthermore, we show that reduction in both age-dependent and age-independent mortality rates drives life extension by DR among the well-studied laboratory model species (yeast, nematode worms, fruit flies and rodents). Our results suggest that convergent adaptation to laboratory conditions better explains the observed DR-longevity relationship than evolutionary conservation although alternative explanations are possible. © 2012 The Authors. Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.\",\n \"title\": \"Comparative and meta-analytic insights into life extension via dietary restriction.\"\n },\n {\n \"docid\": \"MED-3771\",\n \"text\": \"OBJECTIVE: Hyperosmotic stress on cells limits many aspects of cell function, metabolism and health. International data suggest that schoolchildren may be at risk of hyperosmotic stress on cells because of suboptimal water intake. The present study explored the cell hydration status of two samples of children in the USA. DESIGN: Cross-sectional study describing the urine osmolality (an index of hyperosmotic cell shrinkage) and water intake of convenience samples from Los Angeles (LA) and New York City (NYC). SETTING: Each participant collected a urine sample at an outpatient clinic on the way to school on a weekday morning in spring 2009. Each was instructed to wake, eat, drink and do as usual before school, and complete a dietary record form describing the type and amounts of all foods and beverages consumed after waking, before giving the sample. SUBJECTS: The children (9-11 years) in LA (n 337) and NYC (n 211) considered themselves healthy enough to go to school on the day they gave the urine sample. RESULTS: Elevated urine osmolality (>800 mmol/kg) was observed in 63 % and 66 % of participants in LA and NYC, respectively. In multivariable-adjusted logistic regression models, elevated urine osmolality was associated with not reporting intake of drinking water in the morning (LA: OR = 2·1, 95 % CI 1·2, 3·5; NYC: OR = 1·8, 95 % CI 1·0, 3·5). Although over 90 % of both samples had breakfast before giving the urine sample, 75 % did not drink water. CONCLUSIONS: Research is warranted to confirm these results and pursue their potential health implications.\",\n \"title\": \"What is the cell hydration status of healthy children in the USA? Preliminary data on urine osmolality and water intake.\"\n },\n {\n \"docid\": \"MED-4306\",\n \"text\": \"When plasma tryptophan is elevated by the injection of tryptophan or insulin, or by the consumption of carbohydrates, brain tryptophan and serotonin also rise; however, when even larger elevations of plasma tryptophan are produced by the ingestion of protein-containing diets, brain tryptophan and serotonin do not change. The main determinant of brain tryptophan and serotonin concentrations does not appear to be plasma tryptophan alone, but the ratio of this amino acid to other plasma neutral amino acids (that is, tyrosine, phenylalanine, leucine, isoleucine, and valine) that compete with it for uptake into the brain.\",\n \"title\": \"Brain serotonin content: physiological regulation by plasma neutral amino acids.\"\n },\n {\n \"docid\": \"MED-3930\",\n \"text\": \"Studies that have addressed the association between the intake of coffee or caffeine and Parkinson's disease (PD) were conducted mainly in Western countries. Little is known about this relationship in an Asian population. Therefore, we performed an assessment of the association of the intake of coffee, other caffeine-containing beverages, and caffeine with the risk of PD in Japan. The study involved 249 PD cases and 368 control subjects. Information on dietary factors was obtained through a self-administered diet history questionnaire. Adjustment was made for sex, age, region of residence, educational level, pack-years of smoking, body mass index, the dietary glycemic index, and intake of cholesterol, vitamin E, β-carotene, vitamin B(6,) alcohol, and iron. Intake of coffee, black tea, and Japanese and Chinese teas was significantly inversely associated with the risk of PD: the adjusted odds ratios in comparison of the highest with the lowest quartile were 0.52, 0.58, and 0.59, respectively (95% confidence intervals = 0.30-0.90, 0.35-0.97, and 0.35-0.995, respectively). A clear inverse dose-response relationship between total caffeine intake and PD risk was observed. We confirmed that the intake of coffee and caffeine reduced the risk of PD. Furthermore, this is the first study to show a significant inverse relationship between the intake of Japanese and Chinese teas and the risk of PD. Copyright © 2011 Elsevier Ltd. All rights reserved.\",\n \"title\": \"Intake of Japanese and Chinese teas reduces risk of Parkinson's disease.\"\n },\n {\n \"docid\": \"MED-4953\",\n \"text\": \"Objective To evaluate whether intake of protein from animal and vegetable origin is associated with ovulatory infertility. Study Design 18,555 married women without a history of infertility were followed as they attempted a pregnancy or became pregnant during an eight year period. Dietary assessments were related to the incidence of ovulatory infertility. Results During follow-up, 438 women reported ovulatory infertility. The multivariate-adjusted relative risk [RR] (95% CI; P, trend) of ovulatory infertility comparing the highest to the lowest quintile of animal protein intake was 1.39 (1.01 – 1.90; 0.03). The corresponding RR (95% CI; P, trend) for vegetable protein intake was 0.78 (0.54 – 1.12; 0.07). Further, consuming 5% of total energy intake as vegetable protein rather than as animal protein was associated with a more than 50% lower risk of ovulatory infertility (P = 0.007). Conclusions Replacing animal sources of protein with vegetable sources of protein may reduce ovulatory infertility risk.\",\n \"title\": \"Protein intake and ovulatory infertility\"\n },\n {\n \"docid\": \"MED-1611\",\n \"text\": \"A growing body of evidence from observational studies and meta-analyses of the data suggest that diabetes mellitus is associated with an increased risk of cancer. Meta-analyses have shown that diabetes increases the risks of total cancer, and of site-specific cancers of the breast, endometrium, bladder, liver, colorectum and pancreas, and that it decreases the risk of prostate cancer. Insulin resistance and secondary hyperinsulinemia is the most frequently proposed hypothesis, and hyperglycemia itself might promote carcinogenesis. In addition to several facets of lifestyle including obesity, smoking and lack of exercise, treatment for diabetes might affect the risk of cancer. For instance, metformin, an insulin sensitizer, reportedly has a potential anticancer effect. In light of the exploding global epidemic of diabetes, even a modest increase in the cancer risk will translate into a substantial socioeconomic burden. The current insights underscore the need for clinical attention and better-designed studies of the complex interactions between diabetes and cancer.\",\n \"title\": \"Latest insights into the risk of cancer in diabetes\"\n },\n {\n \"docid\": \"MED-3449\",\n \"text\": \"Watercress (Cruciferae), an integral part of Mediterranean diets, is a nutritive food which is used in the treatment of several diseases. Oxidative DNA damage seems to play a crucial role in chronic, aging-related diseases and it is considered an important and probably carcinogenic factor. The aim of this work was to determine the impact of watercress extract on cell viability and its potential antigenotoxic properties against induced oxidative damage, using a comet assay and peripheral blood cells as an in vitro model. An aqueous extract of the leaves was prepared using a juice processor, centrifuged, filtered and preserved at -20 °C. Two concentrations of the aqueous extract (13.2 and 26.4 mg/mL) were assayed. No differences were found in cell viability between the control and treated groups at any time. Significant antigenotoxic effects were observed for both concentrations, expressed as the damage index (p = 0.005 at 30 min; p < 0.001 at 60 and 90 min), the percentage reductions in damage being similar between them (67.1-75.2% respectively). These results suggest that the consumption watercress in the diet is a powerful tool for improving health and the quality of life. Copyright © 2011 John Wiley & Sons, Ltd.\",\n \"title\": \"Antigenotoxic activity of watercress extract in an in vitro mammalian system using comet assay.\"\n },\n {\n \"docid\": \"MED-1582\",\n \"text\": \"Background & Aims Increased intake of dietary fiber has been proposed to reduce risk of inflammatory bowel diseases (Crohn’s disease [CD], ulcerative colitis [UC]). However, few prospective studies have examined associations between long-term intake of dietary fiber and risk of incident CD or UC. Methods We collected and analyzed data from 170,776 women, followed over 26 y, who participated in the Nurses’ Health Study, followed for 3,317,425 person-y. Dietary information was prospectively ascertained via administration of a validated semi-quantitative food frequency questionnaire every 4 y. Self-reported CD and UC were confirmed through review of medical records. Cox proportional hazards models, adjusting for potential confounders, were used to calculate hazard ratios (HRs). Results We confirmed 269 incident cases of CD (incidence 8/100,000 person-y) and 338 cases of UC (incidence 10/100,000 person-y). Compared to the lowest quintile of energy-adjusted cumulative average intake of dietary fiber, intake of the highest quintile (median of 24.3 g/day) was associated with a 40% reduction in risk of CD (multivariate HR for CD, 0.59; 95% confidence interval [CI], 0.39–0.90). This apparent reduction appeared to be greatest for fiber derived from fruits; fiber from cereals, whole grains, or legumes did not modify risk. In contrast, neither total intake of dietary fiber (multivariate HR, 0.82; 95% CI 0.58–1.17) nor intake of fiber from specific sources appeared to be significantly associated with risk of UC. Conclusion Based on data from the Nurses’ Health Study, long-term intake of dietary fiber, particularly from fruit, is associated with lower risk of CD but not UC. Further studies are needed to determine the mechanisms that mediate this association.\",\n \"title\": \"A Prospective Study of Long-term Intake of Dietary Fiber and Risk of Crohn’s Disease and Ulcerative Colitis\"\n },\n {\n \"docid\": \"MED-2662\",\n \"text\": \"A human breast cancer cell line (MCF-7) was used to develop an in vitro screening assay for the detection of xenoestrogenic environmental pollutants. MCF-7 cells were cultured in DMEM containing 5% fetal bovine serum (FBS). An estrogenic response was defined as an increase in the frequency of proliferating MCF-7 cells, and was measured using a thymidine analog, bromodeoxyuridine, and flow cytometry. Di-2-ethylhexyl phthalate (DEHP) and 4-n-nonylphenol (4-n-NP) were used as model chemicals. The proliferation rate of S-phase cells after 24 h of exposure to various concentrations of 17beta-estradiol and to model compounds was compared with a positive and a negative control, containing 1 nM 17beta-estradiol and 0.1% ethanol, respectively. DEHP and 4-n-NP increased the frequency of proliferating MCF-7 cells in a dose-dependent manner. The lowest concentration that significantly increased the proliferation of MCF-7 cells was 10 microM for DEHP and 1 microM for 4-n-NP. The results showed that the assay is accurate and quick to perform. It may prove a valuable tool for screening potential estrogen-mimicking environmental pollutants.\",\n \"title\": \"Effects of xenoestrogenic environmental pollutants on the proliferation of a human breast cancer cell line (MCF-7).\"\n },\n {\n \"docid\": \"MED-5182\",\n \"text\": \"BACKGROUND: Reports of relationships between dietary fibre intake and breast cancer have been inconsistent. Previous cohort studies have been limited by a narrow range of intakes. METHODS: Women who developed invasive breast cancer, 350 post-menopausally and 257 pre-menopausally, during 240,959 person-years of follow-up in the UK Women's Cohort Study (UKWCS) were studied. This cohort has 35,792 subjects with a wide range of exposure to dietary fibre with intakes of total fibre in the lowest quintile of <20 g/day up to >30 g/day in the top quintile. Fibre and breast cancer relationships were explored using Cox regression modelling adjusted for measurement error. Effects of fibre, adjusting for confounders were examined for pre- and post-menopausal women separately. RESULTS: In pre-menopausal, but not post-menopausal women a statistically significant inverse relationship was found between total fibre intake and risk of breast cancer (P for trend = 0.01). The top quintile of fibre intake was associated with a hazard ratio of 0.48 [95% confidence interval (CI) 0.24-0.96] compared with the lowest quintile. Pre-menopausally, fibre from cereals was inversely associated with risk of breast cancer (P for trend = 0.05) and fibre from fruit had a borderline inverse relationship (P for trend = 0.09). A further model including dietary folate strengthened the significance of the inverse relationship between total fibre and pre-menopausal breast cancer. CONCLUSIONS: These findings suggest that in pre-menopausal women, total fibre is protective against breast cancer; in particular, fibre from cereals and possibly fruit.\",\n \"title\": \"Dietary fibre and risk of breast cancer in the UK Women's Cohort Study.\"\n },\n {\n \"docid\": \"MED-1187\",\n \"text\": \"Background and aims: The causes of relapses of ulcerative colitis (UC) are unknown. Dietary factors have been implicated in the pathogenesis of UC. The aim of this study was to determine which dietary factors are associated with an increased risk of relapse of UC. Methods: A prospective cohort study was performed with UC patients in remission, recruited from two district general hospitals, who were followed for one year to determine the effect of habitual diet on relapse. Relapse was defined using a validated disease activity index. Nutrient intake was assessed using a food frequency questionnaire and categorised into tertiles. Adjusted odds ratios for relapse were determined using multivariate logistic regression, controlling for non-dietary factors. Results: A total of 191 patients were recruited and 96% completed the study. Fifty two per cent of patients relapsed. Consumption of meat (odds ratio (OR) 3.2 (95% confidence intervals (CI) 1.3–7.8)), particularly red and processed meat (OR 5.19 (95% CI 2.1–12.9)), protein (OR 3.00 (95% CI 1.25–7.19)), and alcohol (OR 2.71 (95% CI 1.1–6.67)) in the top tertile of intake increased the likelihood of relapse compared with the bottom tertile of intake. High sulphur (OR 2.76 (95% CI 1.19–6.4)) or sulphate (OR 2.6 (95% CI 1.08–6.3)) intakes were also associated with relapse and may offer an explanation for the observed increased likelihood of relapse. Conclusions: Potentially modifiable dietary factors, such as a high meat or alcoholic beverage intake, have been identified that are associated with an increased likelihood of relapse for UC patients. Further studies are needed to determine if it is the sulphur compounds within these foods that mediates the likelihood of relapse and if reducing their intake would reduce relapse frequency.\",\n \"title\": \"Influence of dietary factors on the clinical course of ulcerative colitis: a prospective cohort study\"\n },\n {\n \"docid\": \"MED-3226\",\n \"text\": \"Context and Objective: Dietary intake of animal proteins is associated with an increase in urinary calcium and nephrolithiasis risk. We tested the hypothesis that the acid load imposed by dietary proteins causes this hypercalciuria. Design and Setting: In a short-term crossover metabolic study, an alkali salt was provided with a high-protein diet (HPD) to neutralize the acid load imparted by dietary proteins. Participants and Interventions: Eleven healthy volunteers were evaluated at the end of each of four phases while consuming metabolic diets with fixed calcium and sodium content. Phases 1 and 3 consisted of a control diet (CD). Phases 2 and 4 consisted of a eucaloric HPD (60 g/d animal proteins added to CD). Along with HPD in phases 2 and 4, subjects ingested 30 mEq twice daily of either potassium citrate (KCitrate, alkaline salt) or potassium chloride (KCl, control neutral salt). Results: KCitrate completely neutralized the acid load imparted by HPD (based on changes in urine pH and net acid excretion) and increased urinary citrate. Urinary calcium increased during both HPD phases compared with CD but was not significantly different between the HPD + KCl and HPD + KCitrate phases (182 ± 85 vs. 170 ± 85 mg/d; P = 0.28). Increased urinary saturation with respect to calcium oxalate and uric acid with HPD was abrogated by KCitrate. Conclusions: This study suggests that, at least in the short-term, mechanism(s) other than acid load account for hypercalciuria induced by HPD. The beneficial effect of KCitrate on nephrolithiasis risk with HPD is through correction of declines in urine pH and citrate.\",\n \"title\": \"Hypercalciuria Associated with High Dietary Protein Intake Is Not Due to Acid Load\"\n },\n {\n \"docid\": \"MED-2506\",\n \"text\": \"Long-term caloric restriction (CR) is a robust means of reducing age-related diseases and extending life span in multiple species, but the effects in humans are unknown. The low caloric intake, long life expectancy, and the high prevalence of centenarians in Okinawa have been used as an argument to support the CR hypothesis in humans. However, no long-term, epidemiologic analysis has been conducted on traditional dietary patterns, energy balance, and potential CR phenotypes for the specific cohort of Okinawans who are purported to have had a calorically restricted diet. Nor has this cohort's subsequent mortality experience been rigorously studied. Therefore, we investigated six decades of archived population data on the elderly cohort of Okinawans (aged 65-plus) for evidence of CR. Analyses included traditional diet composition, energy intake, energy expenditure, anthropometry, plasma DHEA, mortality from age-related diseases, and current survival patterns. Findings include low caloric intake and negative energy balance at younger ages, little weight gain with age, life-long low BMI, relatively high plasma DHEA levels at older ages, low risk for mortality from age-related diseases, and survival patterns consistent with extended mean and maximum life span. This study lends epidemiologic support for phenotypic benefits of CR in humans and is consistent with the well-known literature on animals with regard to CR phenotypes and healthy aging.\",\n \"title\": \"Caloric restriction, the traditional Okinawan diet, and healthy aging: the diet of the world's longest-lived people and its potential impact on mor...\"\n },\n {\n \"docid\": \"MED-1254\",\n \"text\": \"OBJECTIVE: To investigate the effect of replacing lean meat with a soy product, tofu, on coronary heart disease risk factors including serum lipoproteins, lipoprotein (a), factor VII, fibrinogen and in vitro susceptibility of LDL to oxidation. DESIGN: A randomized cross over dietary intervention study. SETTING: Free-living individuals studied at Deakin University. SUBJECTS: Forty-five free-living healthy males aged 35 to 62 years completed the dietary intervention. Three subjects were non-compliant and excluded prior to analysis. INTERVENTIONS: A diet containing 150 grams of lean meat per day was compared to a diet containing 290 grams of tofu per day in an isocaloric and isoprotein substitution. Each dietary period was one month duration. RESULTS: Analysis of the seven-day diet record showed that diets were similar in energy, protein, carbohydrate, total fat, saturated and unsaturated fat, polyunsaturated to saturated fat ratio, alcohol and fiber. Total cholesterol and triglycerides were significantly lower, and in vitro LDL oxidation lag phase was significantly longer on the tofu diet compared to the meat diet. The hemostatic factors, factor VII and fibrinogen, and lipoprotein(a) were not significantly affected by the tofu diet. CONCLUSIONS: The increase in LDL oxidation lag phase would be expected to be associated with a decrease in coronary heart disease risk.\",\n \"title\": \"Effect of meat replacement by tofu on CHD risk factors including copper induced LDL oxidation.\"\n },\n {\n \"docid\": \"MED-2272\",\n \"text\": \"To assess the physiologic effects of cherry consumption, we measured plasma urate, antioxidant and inflammatory markers in 10 healthy women who consumed Bing sweet cherries. The women, age 22-40 y, consumed two servings (280 g) of cherries after an overnight fast. Blood and urine samples were taken before the cherry dose, and at 1.5, 3 and 5 h postdose. Plasma urate decreased 5 h postdose, mean +/- SEM = 183 +/- 15 micro mol/L compared with predose baseline of 214 +/- 13 micro mol/L (P < 0.05). Urinary urate increased postdose, with peak excretion of 350 +/- 33 micro mol/mmol creatinine 3 h postdose compared with 202 +/- 13 at baseline (P < 0.01). Plasma C-reactive protein (CRP) and nitric oxide (NO) concentrations had decreased marginally 3 h postdose (P < 0.1), whereas plasma albumin and tumor necrosis factor-alpha were unchanged. The vitamin C content of the cherries was solely as dehydroascorbic acid, but postdose increases in plasma ascorbic acid indicated that dehydroascorbic acid in fruits is bioavailable as vitamin C. The decrease in plasma urate after cherry consumption supports the reputed anti-gout efficacy of cherries. The trend toward decreased inflammatory indices (CRP and NO) adds to the in vitro evidence that compounds in cherries may inhibit inflammatory pathways.\",\n \"title\": \"Consumption of cherries lowers plasma urate in healthy women.\"\n },\n {\n \"docid\": \"MED-2504\",\n \"text\": \"It is well established that the target of rapamycin (TOR) protein kinase has pivotal roles in controlling cell functions (including protein synthesis, cell growth and cell proliferation) and is implicated in numerous human diseases. Mammalian TOR complex 1 (mTORC1) signalling is activated by hormones and growth factors, and is also stimulated by intracellular amino acids. Recent research has provided important new insight into the poorly understood mechanism by which amino acids activate mTORC1 signalling, showing that the protein kinase MAP4K3 and Rag GTPases have important roles in this. mTORC1 is known to control the G1/S transition of the cell cycle: new data show that (m)TORC1 also controls G2/M progression in yeast and mammals, albeit in contrasting ways.\",\n \"title\": \"Nutrient control of TORC1, a cell-cycle regulator.\"\n },\n {\n \"docid\": \"MED-4886\",\n \"text\": \"OBJECTIVES: Previous research has demonstrated that patients with prostate cancer participating in the Prostate Cancer Lifestyle Trial had a reduction in prostate-specific antigen (PSA) levels, inhibition of LNCaP cell growth, and fewer prostate cancer-related clinical events at the end of 1 year compared with controls. The aim of this study was to examine the clinical events in this trial during a 2-year period. METHODS: The Prostate Cancer Lifestyle Trial was a 1-year randomized controlled clinical trial of 93 patients with early-stage prostate cancer (Gleason score <7, PSA 4-10 ng/mL) undergoing active surveillance. The patients in the experimental arm were encouraged to adopt a low-fat, plant-based diet, to exercise and practice stress management, and to attend group support sessions. The control patients received the usual care. RESULTS: By 2 years of follow-up, 13 of 49 (27%) control patients and 2 of 43 (5%) experimental patients had undergone conventional prostate cancer treatment (radical prostatectomy, radiotherapy, or androgen deprivation, P < .05). No differences were found between the groups in other clinical events (eg, cardiac), and no deaths occurred. Three of the treated control patients but none of the treated experimental patients had a PSA level of >or=10 ng/mL, and 1 treated control patient but no treated experimental patients had a PSA velocity of >2 ng/mL/y before treatment. No significant differences were found between the untreated experimental and untreated control patients in PSA change or velocity at the end of 2 years. CONCLUSIONS: Patients with early-stage prostate cancer choosing active surveillance might be able to avoid or delay conventional treatment for at least 2 years by making changes in their diet and lifestyle.\",\n \"title\": \"Clinical events in prostate cancer lifestyle trial: results from two years of follow-up.\"\n },\n {\n \"docid\": \"MED-3271\",\n \"text\": \"Most metastatic tumors, such as those originating in the prostate, lung, and gastrointestinal tract, respond poorly to conventional chemotherapy. Novel treatment strategies for advanced cancer are therefore desperately needed. Dietary restriction of the essential amino acid methionine offers promise as such a strategy, either alone or in combination with chemotherapy or other treatments. Numerous in vitro and animal studies demonstrate the effectiveness of dietary methionine restriction in inhibiting growth and eventually causing death of cancer cells. In contrast, normal host tissues are relatively resistant to methionine restriction. These preclinical observations led to a phase I clinical trial of dietary methionine restriction for adults with advanced cancer. Preliminary findings from this trial indicate that dietary methionine restriction is safe and feasible for the treatment of patients with advanced cancer. In addition, the trial has yielded some preliminary evidence of antitumor activity. One patient with hormone-independent prostate cancer experienced a 25% reduction in serum prostate-specific antigen (PSA) after 12 weeks on the diet, and a second patient with renal cell cancer experienced an objective radiographic response. The possibility that methionine restriction may act synergistically with other cancer treatments such as chemotherapy is being explored. Findings to date support further investigation of dietary methionine restriction as a novel treatment strategy for advanced cancer.\",\n \"title\": \"Can dietary methionine restriction increase the effectiveness of chemotherapy in treatment of advanced cancer?\"\n },\n {\n \"docid\": \"MED-3127\",\n \"text\": \"AIM: Isoflavones in soy foods are part of a larger class of flayonoid compounds that have have been demonstrated to be potent dietary anti-cancer agents, and the effect of soy intake on the survival of ovarian cancer is conflicting. Therefore, we aimed to explore the whether soy intake is related to the risk of death of breast cancer. METHODS: A prospective study was conducted. A total of 256 patients included in this study had breast cancer and were recruited between January 2004 and January 2006. All of them were followed up from since January 2011. A univariate Cox's regression analysis was used to assess the association between soy intake and survival. RESULTS: The education level, menopausal status, ER/PR status and TNM stage were significant difference in the survival of breast cancer. The highest soy isoflavone was associated with a decreased death risk of breast cancer (OR=0.25, 95% CI=0.09-0.54). Moreover, the higher consumption of soy protein also presented a trend decreased breast cancer risk, and the highest consumption significantly reduced the cancer risk compared with the lowest consumption (OR=0.38, 95% CI=0.17-0.86). CONCLUSION: The present study suggests soy intake is associated with a significant reduced death risk of breast cancer in Chinese population. Further large sample studies are warranted to confirm the inverse association of soy consumption and breast cancer survival by menopausal status.\",\n \"title\": \"Study on soy isoflavone consumption and risk of breast cancer and survival.\"\n },\n {\n \"docid\": \"MED-3230\",\n \"text\": \"OBJECTIVE: Diet affects urine pH and acid-base balance. Both excess acid/alkaline ash (EAA) and estimated net acid excretion (NAE) calculations have been used to estimate the effects of diet on urine pH. This study's goal was to determine if free-living vegans, lacto-ovo vegetarians, and omnivores have increasingly acidic urine, and to assess the ability of EAA and estimated NAE calculations to predict urine pH. DESIGN: This study used a cross-sectional design. SETTING AND PARTICIPANTS: This study assessed urine samples of 10 vegan, 16 lacto-ovo vegetarian, and 16 healthy omnivorous women in the Boston metropolitan area. Six 3-day food records from each dietary group were analyzed for EAA content and estimated NAE, and correlations with measured urine pH were calculated. RESULTS: The mean (+/- SD) urine pH was 6.15 +/- 0.40 for vegans, 5.90 +/- 0.36 for lacto-ovo vegetarians, and 5.74 +/- 0.21 for omnivores (analysis of variance, P = .013). Calculated EAA values were not significantly different among the three groups, whereas mean estimated NAE values were significantly different: 17.3 +/- 14.5 mEq/day for vegans, 31.3 +/- 8.5 mEq/day for lacto-ovo vegetarians, and 42.6 +/- 13.2 mEq/day for omnivores (analysis of variance, P = .01). The average deattenuated correlation between urine pH and EAA was 0.333; this value was -0.768 for estimated NAE and urine pH, with a regression equation of pH = 6.33 - 0.014 NAE (P = .02, r = -0.54). CONCLUSIONS: Habitual diet and estimated NAE calculations indicate the probable ranking of urine pH by dietary groups, and may be used to determine the likely acid-base status of an individual; EAA calculations were not predictive of urine pH.\",\n \"title\": \"Estimated net acid excretion inversely correlates with urine pH in vegans, lacto-ovo vegetarians, and omnivores.\"\n },\n {\n \"docid\": \"MED-3235\",\n \"text\": \"Background Maintaining muscle mass while aging is important to prevent falls and fractures. Metabolic acidosis promotes muscle wasting, and the net acid load from diets that are rich in net acid–producing protein and cereal grains relative to their content of net alkali–producing fruit and vegetables may therefore contribute to a reduction in lean tissue mass in older adults. Objective We aimed to determine whether there was an association of 24-h urinary potassium and an index of fruit and vegetable content of the diet with the percentage lean body mass (%LBM) or change in %LBM in older subjects. Design Subjects were 384 men and women ≥65 y old who participated in a 3-y trial comparing calcium and vitamin D with placebo. Potassium was measured in 24-h urine collections at baseline. The %LBM, defined as total body nonfat, nonbone tissue weight ÷ weight × 100, was measured by using dual-energy X-ray absorptiometry at baseline and at 3 y. Physical activity, height, and weight were assessed at baseline and at 3 y. Results At baseline, the mean urinary potassium excretion was 67.0 ± 21.1 mmol/d. Urinary potassium (mmol/d) was significantly positively associated with %LBM at baseline (β = 0.033, P = 0.006; adjusted for sex, weight, and nitrogen excretion) but not with 3-y change in %LBM. Over the 3-y study, %LBM increased by 2.6 ± 3.6%. Conclusion Higher intake of foods rich in potassium, such as fruit and vegetables, may favor the preservation of muscle mass in older men and women.\",\n \"title\": \"Alkaline diets favor lean tissue mass in older adults\"\n },\n {\n \"docid\": \"MED-1618\",\n \"text\": \"To study the effect of a moderate increase in insulin secretion produced by an increased daily protein intake on dehydroepiandrosterone sulfate (DHEAS), a balanced randomized crossover trial consisting of three strictly controlled dietary regimens was performed in six healthy male volunteers. The basic diet (B) contained 50 g protein/d; diets P and M (also basic diets) were enriched with either 32 g protein/d (P) or 10 mmol L-methionine/d (M). Methionine was given (as a specific nonprotein source of endogenously derived sulfate) to control for possible confounding effects on DHEAS due to an increased sulfate supply. At the end of each 4-day diet period, blood and 24-hour urine samples were collected. Fasting plasma levels of testosterone, cortisol, insulin-like growth factor-I (IGF-I), and insulin, as well as urinary output of total (hot acid-cleaved) testosterone conjugates and 3alpha-androstanediol glucuronide, did not show significant changes in response to dietary manipulations. Endogenous sulfate availability (as reflected by renal sulfate output per 24 hours) approximately doubled with diets P and M. However, plasma levels (6.3 +/- 1.5, 6.8 +/- 1.8, and 6.9 +/- 2.1 micromol/L for B, P, and M, respectively) and urinary excretion (8.8 +/- 9.8, 9.4 +/- 11.2, 8.0 +/- 8.3 micromol/d) of DHEAS remained unaffected. Considering the clear increments (P < .01) in urinary C-peptide excretion with diet P (20.4 +/- 10.3 nmol/d) versus diets B and M (12.6 +/- 5.1 and 13.2 +/- 3.6 nmol/d), respectively, our results suggest that a moderately strong diet-induced increase in daily insulin secretion does not alter urinary and plasma levels of DHEAS.\",\n \"title\": \"A moderate increase in daily protein intake causing an enhanced endogenous insulin secretion does not alter circulating levels or urinary excretion...\"\n },\n {\n \"docid\": \"MED-2208\",\n \"text\": \"BACKGROUND: Bikunin, a Kunitz-type protease inhibitor, specifically inhibits tumor invasion and metastasis. METHODS: The authors initially evaluated the therapeutic efficacy of once-daily oral administration of different doses of bikunin against human ovarian carcinoma HRA cells growing in the peritonea of nude mice. For the in vivo studies, female 7-week-old nude mice were randomized to 1 of 4 groups: bikunin-treated groups (n = 9 in each group) received 3, 10, or 30 microg/g body weight per day bikunin for 7 days via gastrointestinal gavage, and a control group (n = 9) received the vehicle solution (phosphate-buffered saline) via gastrointestinal gavage. On Day 9, the abdominal cavity was examined by two observers who were blinded to treatment. RESULTS: After oral administration, intact bikunin was detectable in mouse serum specimens at 3 and 6 hours. This was followed by a decline at 12 hours. The mice given bikunin at the highest dose level had a 40% decrease in tumor load. The highest uptake in the tumor was obtained with [125I]bikunin 12 hours postadministration. No effect on either food intake or body weight was observed in the treated versus sham groups. The current study was the first to report the potent activity of once-daily oral administration of bikunin against ovarian carcinoma. Next, the authors performed a Phase I trial to determine the maximum-tolerated dose (MTD) and safety of a once-daily oral administration schedule. The indication was locally advanced uterine cervical carcinoma after definitive treatment. An escalating dose (3, 10, and 30 mg/kg per day) of bikunin was administered orally to nine patients for 7 days. There were no dose-limiting toxicities and the MTD of the bikunin schedule was not defined. The authors also obtained preliminary data on its effect on urokinase-type plasminogen activator expression at the highest dose level. CONCLUSIONS: Once-daily oral administration of bikunin was found to be safe in humans and exhibited signs of biologic activity. Copyright 2004 American Cancer Society.\",\n \"title\": \"Therapeutic efficacy of once-daily oral administration of a Kunitz-type protease inhibitor, bikunin, in a mouse model and in human cancer.\"\n },\n {\n \"docid\": \"MED-1226\",\n \"text\": \"Background Several components of dairy products have been linked to earlier menarche. Methods/Findings This study assessed whether positive associations exist between childhood milk consumption and age at menarche or the likelihood of early menarche (<12 yrs) in a U.S sample. Data derive from the National Health and Nutrition Examination Survey (NHANES) 1999–2004. Two samples were utilized: 2657 women age 20–49 yrs and 1008 girls age 9–12 yrs. In regression analysis, a weak negative relationship was found between frequency of milk consumption at 5–12 yrs and age at menarche (daily milk intake β = −0.32, P<0.10; “sometimes/variable milk intake” β = −0.38, P<0.06, each compared to intake rarely/never). Cox regression yielded no greater risk of early menarche among those who drank milk “sometimes/varied” or daily vs. never/rarely (HR: 1.20, P<0.42, HR: 1.25, P<0.23, respectively). Among the 9–12 yr olds, Cox regression indicated that neither total dairy kcal, calcium and protein, nor daily milk intake in the past 30 days contributed to early menarche. Girls in the middle tertile of milk intake had a marginally lower risk of early menarche than those in the highest tertile (HR: 0.6, P<0.06). Those in the lowest tertiles of dairy fat intake had a greater risk of early menarche than those in the highest (HR: 1.5, P<0.05, HR: 1.6, P<0.07, lowest and middle tertile, respectively), while those with the lowest calcium intake had a lower risk of early menarche (HR: 0.6, P<0.05) than those in the highest tertile. These relationships remained after adjusting for overweight or overweight and height percentile; both increased the risk of earlier menarche. Blacks were more likely than Whites to reach menarche early (HR: 1.7, P<0.03), but not after controlling for overweight. Conclusions There is some evidence that greater milk intake is associated with an increased risk of early menarche, or a lower age at menarche.\",\n \"title\": \"Milk Intake and Total Dairy Consumption: Associations with Early Menarche in NHANES 1999-2004\"\n },\n {\n \"docid\": \"MED-2290\",\n \"text\": \"Background Differences in nutrient profiles between vegetarian and non vegetarian dietary patterns reflect nutritional differences that may contribute to the development of disease. Objective To compare nutrient intakes between dietary patterns characterized by consumption or exclusion of meat and dairy products. Design Cross-sectional study of 71751 subjects (mean age 59 years) from the Adventist-Health-Study-2. Data was collected between 2002 and 2007. Participants completed a 204-item validated semi-quantitative food frequency questionnaire. Dietary patterns compared were: non vegetarian, semi vegetarian, pesco vegetarian, lacto-ovo vegetarian and strict vegetarian. ANCOVA was used to analyze differences in nutrient intakes by dietary patterns and were adjusted for age, and sex and race. BMI and other relevant demographic data were reported and compared by dietary pattern using chi-square tests and ANOVA. Results Many nutrient intakes varied significantly between dietary patterns. Non vegetarians had the lowest intakes of plant proteins, fiber, β-Carotene, and Mg than those following vegetarian dietary patterns and the highest intakes of saturated, trans, arachidonic, and docosahexaenoic fatty acids. The lower tails of some nutrient distributions in strict vegetarians suggested inadequate intakes by a portion of the subjects. Energy intake was similar among dietary patterns at close to 2000 kcal/d with the exception of semi vegetarians that had an intake of 1713 kcal/d. Mean BMI was highest in non-vegetarians (mean; standard deviation [SD]) (28.7; [6.4]) and lowest in strict vegetarians (24.0; [4.8]). Conclusions Nutrient profiles varied markedly between dietary patterns that were defined by meat and dairy intakes. These differences can be of interest in the etiology of obesity and chronic diseases.\",\n \"title\": \"Nutrient Profiles of Vegetarian and Non Vegetarian Dietary Patterns\"\n },\n {\n \"docid\": \"MED-1722\",\n \"text\": \"Overexpression of growth factors and/or their receptors is a common event in malignancy and provides the underlying mechanisms for one of the hallmarks of cancer, uncontrolled proliferation. Mounting evidence suggests that IGF-1 is involved in the pathogenesis and progression of different types of human cancer such as colon, breast, prostate and lung. However, only a few studies have investigated the association between IGF-1 levels and childhood cancer risk. We aimed to compare the IGF-1 serum level in children with de novo malignancies to healthy children, and to assess its relationship with cancer type, stage, metastasis and different disease characteristics. The study was carried out on 100 children; 50 children with de novo malignancies and 50 healthy children of matched age and gender as a control group. The patients were subjected to a routine work-up for their cancers according to our local standards. Estimation of the serum level of IGF-1 was carried out in the two groups using ELISA. Our results showed that children with cancer had significantly higher levels of IGF-1 than healthy controls of the same age and gender. No association was found between IGF-1 and tumor type, stage, metastasis and other disease characteristics. In conclusion, the IGF-1 serum level is an important indicator of risk for the most prevalent forms of childhood cancer. It may be used to identify children at the highest risk for these cancers and aid in determing who may benefit most from preventive strategies. Given the small number of children in our study, studies with larger populations are required to confirm these results.\",\n \"title\": \"Insulin-like growth factor-1 and childhood cancer risk\"\n },\n {\n \"docid\": \"MED-2649\",\n \"text\": \"Background Dietary fat exerts numerous complex effects on proinflammatory and immunologic pathways. Several epidemiological studies have examined the relationships between intake of fatty acids and/or foods high in fat and allergic rhinitis, but have provided conflicting findings. The current cross-sectional study investigated such relationships in Japan. Methods Study subjects were 1745 pregnant women. The definition of rhinoconjunctivitis was based on criteria from the International Study of Asthma and Allergies in Childhood. Information on dietary factors was collected using a validated self-administered diet history questionnaire. Adjustment was made for age; gestation; region of residence; number of older siblings; number of children; smoking; secondhand smoke exposure at home and at work; family history of asthma, atopic eczema, and allergic rhinitis; household income; education; and body mass index. Results The prevalence of rhinoconjunctivitis in the past 12 months was 25.9%. Higher meat intake was significantly associated with an increased prevalence of rhinoconjunctivitis: the adjusted odds ratio between extreme quartiles was 1.71 (95% confidence interval: 1.25-2.35, P for trend = 0.002). No measurable association was found between fish intake and rhinoconjunctivitis. Intake of total fat, saturated fatty acids, monounsaturated fatty acids, n-3 polyunsaturated fatty acids, α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, n-6 polyunsaturated fatty acids, linoleic acid, arachidonic acid, and cholesterol and the ratio of n-3 to n-6 polyunsaturated fatty acid intake were not evidently related to the prevalence of rhinoconjunctivitis. Conclusions The current results suggest that meat intake may be positively associated with the prevalence of rhinoconjunctivitis in young adult Japanese women.\",\n \"title\": \"Dietary meat and fat intake and prevalence of rhinoconjunctivitis in pregnant Japanese women: baseline data from the Kyushu Okinawa Maternal and Child Health Study\"\n },\n {\n \"docid\": \"MED-2646\",\n \"text\": \"BACKGROUND: Certain foods may increase or decrease the risk of developing asthma, rhinoconjunctivitis and eczema. We explored the impact of the intake of types of food on these diseases in Phase Three of the International Study of Asthma and Allergies in Childhood. METHODS: Written questionnaires on the symptom prevalence of asthma, rhinoconjunctivitis and eczema and types and frequency of food intake over the past 12 months were completed by 13-14-year-old adolescents and by the parents/guardians of 6-7-year-old children. Prevalence ORs were estimated using logistic regression, adjusting for confounders, and using a random (mixed) effects model. RESULTS: For adolescents and children, a potential protective effect on severe asthma was associated with consumption of fruit ≥3 times per week (OR 0.89, 95% CI 0.82 to 0.97; OR 0.86, 95% CI 0.76 to 0.97, respectively). An increased risk of severe asthma in adolescents and children was associated with the consumption of fast food ≥3 times per week (OR 1.39, 95% CI 1.30 to 1.49; OR 1.27, 95% CI 1.13 to 1.42, respectively), as well as an increased risk of severe rhinoconjunctivitis and severe eczema. Similar patterns for both ages were observed for regional analyses, and were consistent with gender and affluence categories and with current symptoms of all three conditions. CONCLUSIONS: If the association between fast foods and the symptom prevalence of asthma, rhinoconjunctivitis and eczema is causal, then the findings have major public health significance owing to the rising consumption of fast foods globally.\",\n \"title\": \"Do fast foods cause asthma, rhinoconjunctivitis and eczema? Global findings from the International Study of Asthma and Allergies in Childhood (ISAA...\"\n },\n {\n \"docid\": \"MED-1610\",\n \"text\": \"The effects of three different meat-containing breakfast meals (pork, beef or chicken) on acute satiety and appetite regulatory hormones were compared using a within-subjects study design. Thirty fasting non-smoking pre-menopausal women attended a research centre on three test days to consume, a meat-containing meal matched in energy (kJ) and protein content, palatability, and appearance. No difference was found between meat groups for either energy intake or macronutrient profile of food consumed at a subsequent ad libitum buffet lunch, or over the rest of the day. Visual Analogue Scale (VAS) ratings for hunger and satiety over an 180 min period did not differ between test meals. After consumption of the test meals, a significant difference was found in PYY response between pork and chicken meals (P=0.027) but not for levels of CCK, ghrelin, insulin or glucose. This study positions pork, beef, and chicken as equal in their effect on satiety and release of appetite-related intestinal hormones and of insulin. Copyright © 2010 Elsevier Ltd. All rights reserved.\",\n \"title\": \"Pork, beef and chicken have similar effects on acute satiety and hormonal markers of appetite.\"\n },\n {\n \"docid\": \"MED-3464\",\n \"text\": \"The purpose of this study was to determine the effects of consuming sweet cherries on plasma lipids and markers of inflammation in healthy humans. Healthy men and women (n = 18) supplemented their diets with Bing sweet cherries (280 g/d) for 28 d. After a 12-h fast, blood samples were taken before the start of cherry consumption (study d 0 and 7), 14 and 28 d after the start of cherry supplementation (study d 21 and 35), and 28 d after the discontinuation (study d 64) of cherry consumption. After cherries were consumed for 28 d, circulating concentrations of C-reactive protein (CRP), regulated upon activation, normal T-cell expressed, and secreted (RANTES), and NO decreased by 25 (P < 0.05), 21 (P < 0.05), and 18% (P = 0.07) respectively. After the discontinuation of cherry consumption for 28 d (d 64), concentrations of RANTES continued to decrease (P = 0.001), whereas those of CRP and NO did not differ from either d 7 (pre-cherries) or d 35 (post-cherries). Plasma concentrations of IL-6 and its soluble receptor, intercellular adhesion molecule-1, and tissue inhibitor of metalloproteinases-2 did not change during the study. Cherry consumption did not affect the plasma concentrations of total-, HDL-, LDL-, and VLDL- cholesterol, triglycerides, subfractions of HDL, LDL, VLDL, and their particle sizes and numbers. It also did not affect fasting blood glucose or insulin concentrations or a number of other chemical and hematological variables. Results of the present study suggest a selective modulatory effect of sweet cherries on CRP, NO, and RANTES. Such anti-inflammatory effects may be beneficial for the management and prevention of inflammatory diseases.\",\n \"title\": \"Consumption of Bing sweet cherries lowers circulating concentrations of inflammation markers in healthy men and women.\"\n },\n {\n \"docid\": \"MED-2362\",\n \"text\": \"The study of the expression of Gal alpha 1----3Gal beta 1----4GlcNAc residues on mammalian glycoconjugates is of particular interest since as many as 1% of circulating IgG antibodies in man (the natural anti-Gal antibody) interact specifically with this carbohydrate residue. In recent studies, we have found that Gal alpha 1----3Gal beta 1----4GlcNAc residues are abundant on red cells and nucleated cells of nonprimate mammals, prosimians, and New World monkeys, but their expression is diminished in Old World monkeys, apes, and humans. In the present work, we have analyzed the expression of these residues on secreted mammalian glycoproteins. For this purpose, we have developed a radioimmunoassay (RIA) which enables the quantification of Gal alpha 1----3Gal beta 1----4GlcNAc residues on the secreted glycoproteins. Purified biotinylated anti-Gal was used as the antibody in the RIA, and bovine thyroglobulin enriched for Gal alpha 1----3Gal beta 1----4GlcNAc residues served as a solid-phase antigen. In this study, it is reported for the first time that the evolutionary pattern of Gal alpha 1----3Gal beta 1----4GlcNAc residue distribution in in vivo secreted glycoproteins is similar to that observed in membranes of cell lines and of red cells. Thyroglobulin, fibrinogen, or IgG molecules from nonprimate mammals and from New World monkeys express varying amounts of Gal alpha 1----3Gal beta 1----4GlcNAc residues ranging between 0.01 and 11 residues per molecule, whereas no such residues are present on any of these glycoproteins of human or Old World monkey origin.(ABSTRACT TRUNCATED AT 250 WORDS)\",\n \"title\": \"Distribution of Gal alpha 1----3Gal beta 1----4GlcNAc residues on secreted mammalian glycoproteins (thyroglobulin, fibrinogen, and immunoglobulin G...\"\n },\n {\n \"docid\": \"MED-3149\",\n \"text\": \"Many health conditions are treated, at least in part, by therapeutic diets. Although the success of any intervention depends on its acceptability to the patient, the acceptability of therapeutic diets and factors that influence it have been largely neglected in nutrition research. A working definition of acceptability is proposed and an examination and summary are provided of available data on the acceptability of common diet regimens used for medical conditions. The goal is to suggest ways to improve the success of therapeutic diets. The proposed working definition of \\\"acceptability\\\" refers to the user's judgment of the advantages and disadvantages of a therapeutic diet-in relation to palatability, costs, and effects on eating behaviour and health-that influence the likelihood of adherence. Very low-calorie, reduced-fat omnivorous, vegetarian and vegan, and low-carbohydrate diets all achieve acceptability among the majority of users in studies of up to one year, in terms of attrition and adherence rates and results of questionnaires assessing eating behaviours. Longer studies are fewer, but they suggest that vegetarian, vegan, and reduced-fat diets are acceptable, as indicated by sustained changes in nutrient intake. Few studies of this length have been published for very low-calorie or low-carbohydrate diets. Long-term studies of adherence and acceptability of these and other therapeutic diets are warranted.\",\n \"title\": \"Four therapeutic diets: adherence and acceptability.\"\n },\n {\n \"docid\": \"MED-3774\",\n \"text\": \"While dehydration has well-documented negative effects on adult cognition, there is little research on hydration and cognitive performance in children. We investigated whether having a drink of water improved children's performance on cognitive tasks. Fifty-eight children aged 7-9 years old were randomly allocated to a group that received additional water or a group that did not. Results showed that children who drank additional water rated themselves as significantly less thirsty than the comparison group (p=0.002), and they performed better on visual attention tasks (letter cancellation, p=0.02; spot the difference memory tasks, ps=0.019 and 0.014).\",\n \"title\": \"Should children drink more water?: the effects of drinking water on cognition in children.\"\n },\n {\n \"docid\": \"MED-2763\",\n \"text\": \"Despite compelling statistics that show we could eliminate 80%of all heart disease and strokes, 90% of all diabetes, and 60% of all cancers with basic lifestyle changes, we have failed to motivate the public to make these changes and failed to motivate policy makers to make healthy choices the easiest choice. Dr. Katz suggests we have failed because we have focused too much on statistics and too little on passion. He implores all of us to tap into people's passion by connecting each of these statistics with a human story.\",\n \"title\": \"Facing the facelessness of public health: what's the public got to do with it?\"\n },\n {\n \"docid\": \"MED-2291\",\n \"text\": \"PURPOSE: This review focuses on the health benefits of viscous versus nonviscous soluble fibers, why symptoms can occur with increased fiber consumption, and how to avoid symptoms to improve adherence with a high-fiber diet. DATA SOURCES: Review of scientific literature as well as evidence-based guidelines and resources. CONCLUSIONS: While it is generally known that \\\"fiber is good for you,\\\" it is less well known that specific health benefits are associated with specific fiber characteristics. Many of the health benefits of fiber can be directly correlated with the viscosity of soluble fibers when hydrated (i.e., gel-forming). A reduction in viscosity of a given fiber will attenuate these health benefits, and a nonviscous fiber does not exhibit these health benefits. IMPLICATIONS FOR PRACTICE: Increasing the viscosity of chyme with a viscous soluble fiber has been shown clinically to lower cholesterol for cardiovascular health, improve glycemic control in type 2 diabetes, normalize stool form in both constipation (softens hard stool) and diarrhea (firms loose/liquid stool), and improve the objective clinical measures of metabolic syndrome (glycemic control, lipoprotein profile, body mass index/weight loss, and blood pressure). ©2012 The Author(s) Journal compilation ©2012 American Academy of Nurse Practitioners.\",\n \"title\": \"Viscous versus nonviscous soluble fiber supplements: mechanisms and evidence for fiber-specific health benefits.\"\n },\n {\n \"docid\": \"MED-3457\",\n \"text\": \"Reactive oxygen species produced during vigorous exercise may permeate into cell nuclei and induce oxidative DNA damage, but the supporting evidence is still lacking. By using a 42 km marathon race as a model of massive aerobic exercise, we demonstrated a significant degree of unrepaired DNA base oxidation in peripheral immunocompetent cells, despite a concurrent increase in the urinary excretion of 8-hydroxy-2'-deoxyguanosine. Single cell gel electrophoresis with the incorporation of lesion-specific endonucleases further revealed that oxidized pyrimidines (endonuclease III-sensitive sites) contributed to most of the postexercise nucleotide oxidation. The oxidative DNA damage correlated significantly with plasma levels of creatinine kinase and lipid peroxidation metabolites, and lasted for more than 1 week following the race. This phenomenon may be one of the mechanisms behind the immune dysfunctions after exhaustive exercise.\",\n \"title\": \"Oxidative DNA damage in human peripheral leukocytes induced by massive aerobic exercise.\"\n },\n {\n \"docid\": \"MED-4290\",\n \"text\": \"BACKGROUND AND AIMS: Nut intake has been inversely related to body mass index (BMI) in prospective studies. We examined dietary determinants of adiposity in an elderly Mediterranean population with customarily high nut consumption. METHODS AND RESULTS: A cross-sectional study was conducted in 847 subjects (56% women, mean age 67 years, BMI 29.7kg/m(2)) at high cardiovascular risk recruited into the PREDIMED study. Food consumption was evaluated by a validated semi-quantitative questionnaire, energy expenditure in physical activity by the Minnesota Leisure Time Activity questionnaire, and anthropometric variables by standard measurements. Nut intake decreased across quintiles of both BMI and waist circumference (P-trend <0.005; both). Alcohol ingestion was inversely related to BMI (P-trend=0.020) and directly to waist (P-trend=0.011), while meat intake was directly associated with waist circumference (P-trend=0.018). In fully adjusted multivariable models, independent dietary associations of BMI were the intake of nuts inversely (P=0.002) and that of meat and meat products directly (P=0.042). For waist circumference, independent dietary associations were intake of nuts (P=0.002) and vegetables (P=0.040), both inversely, and intake of meat and meat products directly (P=0.009). From the regression coefficients, it was predicted that BMI and waist circumference decreased by 0.78kg/m(2) and 2.1cm, respectively, for each serving of 30g of nuts. Results were similar in men and women. CONCLUSION: Nut consumption was inversely associated with adiposity independently of other lifestyle variables. It remains to be explored whether residual confounding related to a healthier lifestyle of nut eaters might in part explain these results. Copyright © 2009 Elsevier B.V. All rights reserved.\",\n \"title\": \"Cross-sectional association of nut intake with adiposity in a Mediterranean population.\"\n },\n {\n \"docid\": \"MED-3314\",\n \"text\": \"OBJECTIVES: Evidence suggests that certain occupations and related exposures may increase the risk of malignant lymphoma. Farming, printing and paper industry, wood processing, meat handling and processing, welding, shoe and leather manufacturing and teaching profession are among the categories that have been implicated in previous studies. The relationship between occupation and malignant lymphoma has been investigated in a large European prospective study. METHODS: We investigated occupational risks for lymphomas in the European Prospective Investigation into Cancer and Nutrition (EPIC). The mean follow-up time for 348,555 subjects was 9 years (SD: 2 years). The analysis was based on 866 and 48 newly diagnosed cases of non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL). These were identified in the EPIC subcohorts with occupational data. Data on 52 occupations were collected through standardised questionnaires. Cox proportional hazard models were used to explore the association between occupation and risk of malignant lymphoma. RESULTS: The following occupations were positively associated with malignant NHL after adjustment for study centre, age, sex, socioeconomic status (SES), smoking and alcohol: butchers (HR=1.53, 95% CI 1.05 to 2.48, including multiple myeloma/plasmacytoma; HR=1.30, 95% CI 1.00 to 2.66, excluding multiple myeloma/plasmacytoma) and car repair workers (HR=1.50, 95% CI 1.01 to 2.00, including multiple myeloma/plasmacytoma; HR=1.51, 95% CI 1.01 to 2.31, excluding multiple myeloma/plasmacytoma). HL was associated with gasoline station occupation (HR=4.59, 95% CI 1.08 to 19.6). CONCLUSION: The findings in this current study of a higher risk of NHL among car repair workers and butchers and a higher risk of HL among gasoline station workers suggest a possible role from occupationally related exposures, such as solvents and zoonotic viruses, as risk factors for malignant lymphoma.\",\n \"title\": \"Occupation and risk of lymphoma: a multicentre prospective cohort study (EPIC).\"\n },\n {\n \"docid\": \"MED-3135\",\n \"text\": \"Background: Only 5% of all breast cancers are the result of BRCA1/2 mutations. Methylation silencing of tumor suppressor genes is well described in sporadic breast cancer; however, its role in familial breast cancer is not known. Methods: CpG island promoter methylation was tested in the initial random periareolar fine-needle aspiration sample from 109 asymptomatic women at high risk for breast cancer. Promoter methylation targets included RARB (M3 and M4), ESR1, INK4a/ARF, BRCA1, PRA, PRB, RASSF1A, HIN-1, and CRBP1. Results: Although the overall frequency of CpG island promoter methylation events increased with age (P < 0.0001), no specific methylation event was associated with age. In contrast, CpG island methylation of RARB M4 (P = 0.051), INK4a/ARF (P = 0.042), HIN-1 (P = 0.044), and PRA (P = 0.032), as well as the overall frequency of methylation events (P = 0.004), was associated with abnormal Masood cytology. The association between promoter methylation and familial breast cancer was tested in 40 unaffected premenopausal women in our cohort who underwent BRCA1/2 mutation testing. Women with BRCA1/2 mutations had a low frequency of CpG island promoter methylation (15 of 15 women had ≤4 methylation events), whereas women without a mutation showed a high frequency of promoter methylation events (24 of 25 women had 5-8 methylation events; P < 0.0001). Of women with a BRCA1/2 mutation, none showed methylation of HIN-1 and only 1 of 15 women showed CpG island methylation of RARB M4, INK4a/ARF, or PRB promoters. Conclusions: This is the first evidence of CpG island methylation of tumor suppressor gene promoters in non-BRCA1/2 familial breast cancer.\",\n \"title\": \"CpG Island Tumor Suppressor Promoter Methylation in Non-BRCA-Associated Early Mammary Carcinogenesis\"\n },\n {\n \"docid\": \"MED-4559\",\n \"text\": \"The cardiovascular risk reduction associated with different statins for the prevention of cardiovascular disease and the cardiovascular risk increase associated with excess dietary intake of fat have been quantified. However, these relative risks have never been directly juxtaposed to determine whether an increase in relative risk by 1 activity could be neutralized by an opposing change in relative risk from a second activity. The investigators compared the increase in relative risk for cardiovascular disease associated with the total fat and trans fat content of fast foods against the relative risk decrease provided by daily statin consumption from a meta-analysis of statins in primary prevention of coronary artery disease (7 randomized controlled trials including 42,848 patients). The risk reduction associated with the daily consumption of most statins, with the exception of pravastatin, is more powerful than the risk increase caused by the daily extra fat intake associated with a 7-oz hamburger (Quarter Pounder) with cheese and a small milkshake. In conclusion, statin therapy can neutralize the cardiovascular risk caused by harmful diet choices. In other spheres of human activity, individuals choosing risky pursuits (motorcycling, smoking, driving) are advised or compelled to use measures to minimize the risk (safety equipment, filters, seatbelts). Likewise, some individuals eat unhealthily. Routine accessibility of statins in establishments providing unhealthy food might be a rational modern means to offset the cardiovascular risk. Fast food outlets already offer free condiments to supplement meals. A free statin-containing accompaniment would offer cardiovascular benefits, opposite to the effects of equally available salt, sugar, and high-fat condiments. Although no substitute for systematic lifestyle improvements, including healthy diet, regular exercise, weight loss, and smoking cessation, complimentary statin packets would add, at little cost, 1 positive choice to a panoply of negative ones.\",\n \"title\": \"Can a statin neutralize the cardiovascular risk of unhealthy dietary choices?\"\n },\n {\n \"docid\": \"MED-3348\",\n \"text\": \"Fruit and vegetable consumption is inadequate among adults in the United States; this contributes to preventable morbidity and mortality. More effective dietary intervention strategies are needed. Recently, interventions that advertise the consequences of behavior for appearance have been successful in modifying sun-exposure habits and tobacco use. Such an approach might also facilitate dietary improvement. Consumption of carotenoid-rich fruit and vegetables positively affects skin color, which influences perceptions of health and attractiveness, and promoting such an effect may motivate target audiences to increase consumption of this important food group. This approach represents a novel direction for the field and is potentially suitable for cost-effective, population-level dissemination through the visual media.\",\n \"title\": \"Appealing to Vanity: Could Potential Appearance Improvement Motivate Fruit and Vegetable Consumption?\"\n },\n {\n \"docid\": \"MED-2336\",\n \"text\": \"Accumulated evidence shows that some phytochemicals provide beneficial effects for human health. Recently, a number of mechanistic studies have revealed that direct interactions between phytochemicals and functional proteins play significant roles in exhibiting their bioactivities. However, their binding selectivities to biological molecules are considered to be lower due to their small and simple structures. In this study, we found that zerumbone, a bioactive sesquiterpene, binds to numerous proteins with little selectivity. Similar to heat-denatured proteins, zerumbone-modified proteins were recognized by heat shock protein 90, a constitutive molecular chaperone, leading to heat shock factor 1-dependent heat shock protein induction in hepa1c1c7 mouse hepatoma cells. Furthermore, oral administration of this phytochemical up-regulated heat shock protein expressions in the livers of Sprague-Dawley rats. Interestingly, pretreatment with zerumbone conferred a thermoresistant phenotype to hepa1c1c7 cells as well as to the nematode Caenorhabditis elegans. It is also important to note that several phytochemicals with higher hydrophobicity or electrophilicity, including phenethyl isothiocyanate and curcumin, markedly induced heat shock proteins, whereas most of the tested nutrients did not. These results suggest that non-specific protein modifications by xenobiotic phytochemicals cause mild proteostress, thereby inducing heat shock response and leading to potentiation of protein quality control systems. We considered these bioactivities to be xenohormesis, an adaptation mechanism against xenobiotic chemical stresses. Heat shock response by phytochemicals may be a fundamental mechanism underlying their various bioactivities.\",\n \"title\": \"Non-Specific Protein Modifications by a Phytochemical Induce Heat Shock Response for Self-Defense\"\n },\n {\n \"docid\": \"MED-4920\",\n \"text\": \"BACKGROUND: Celiac disease (CD) is an immune-mediated enteropathic condition triggered in genetically susceptible individuals by the ingestion of gluten. Although common in Europe, CD is thought to be rare in the United States, where there are no large epidemiologic studies of its prevalence. The aim of this study was to determine the prevalence of CD in at-risk and not-at-risk groups in the United States. METHODS: Serum antigliadin antibodies and anti-endomysial antibodies (EMA) were measured. In EMA-positive subjects, human tissue transglutaminase IgA antibodies and CD-associated human leukocyte antigen DQ2/DQ8 haplotypes were determined. Intestinal biopsy was recommended and performed whenever possible for all EMA-positive subjects. A total of 13 145 subjects were screened: 4508 first-degree and 1275 second-degree relatives of patients with biopsy-proven CD, 3236 symptomatic patients (with either gastrointestinal symptoms or a disorder associated with CD), and 4126 not-at-risk individuals. RESULTS: In at-risk groups, the prevalence of CD was 1:22 in first-degree relatives, 1:39 in second-degree relatives, and 1:56 in symptomatic patients. The overall prevalence of CD in not-at-risk groups was 1:133. All the EMA-positive subjects who underwent intestinal biopsy had lesions consistent with CD. CONCLUSIONS: Our results suggest that CD occurs frequently not only in patients with gastrointestinal symptoms, but also in first- and second-degree relatives and patients with numerous common disorders even in the absence of gastrointestinal symptoms. The prevalence of CD in symptomatic patients and not-at-risk subjects was similar to that reported in Europe. Celiac disease appears to be a more common but neglected disorder than has generally been recognized in the United States.\",\n \"title\": \"Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: a large multicenter study.\"\n },\n {\n \"docid\": \"MED-1719\",\n \"text\": \"OBJECTIVE: Overexpression of IGF-I occurs in tumors diagnosed in childhood (osteosarcoma, Wilms tumor, neuroblastoma, etc.) and in adults (breast, ovaries, colon and prostate cancer). The aim of our study was to establish the prevalence of malignancies in states of congenital IGF-I deficiency. SUBJECTS: We surveyed 222 patients with congenital IGF-I deficiency (Laron syndrome, GH gene deletion, GHRH receptor defects and IGF-I resistance) and 338 first and second-degree relatives. RESULTS: None of the IGF-I deficient patients had cancer, whereas 9-24% of the family members had a history of malignancy. CONCLUSIONS: Congenital IGF-I deficiency acts as a protecting factor for the development of cancer.\",\n \"title\": \"Patients with congenital deficiency of IGF-I seem protected from the development of malignancies: a preliminary report.\"\n },\n {\n \"docid\": \"MED-1613\",\n \"text\": \"The present study was designed to examine the effects of habitual consumption of Taiwanese vegetarian diets on hormonal secretion, and on lipid and glycaemic control. Of the ninety-eight healthy female adults recruited from Hualien, Taiwan (aged 31-45 years), forty-nine were Buddhist lactovegetarians and forty-nine were omnivores. Dietary intakes were measured, and blood levels of nutrients and hormones were analysed. Vegetarians consumed less energy, fat and protein, but more fibre than the omnivores. Compared with the omnivores, the vegetarians had, on average, lower BMI and smaller waist circumference. Except for slightly lower levels of thyroxine (T4) in vegetarians, vegetarians and omnivores both showed similar levels of triiodothyronine (T3), free T4, thyroid-stimulating hormone, T3:T4 ratio and cortisol. Compared with the omnivores, the vegetarians had significantly lower levels of fasting insulin (median: 35.3 v. 50.6 pmol/l) and plasma glucose (mean: 4.7 (se 0.05) v. 4.9 (se 0.05) mmol/l). Insulin resistance, as calculated by the homeostasis model assessment method, was significantly lower in the vegetarians than in the omnivores (median: 1.10 v. 1.56), while beta-cell function was not different between the two groups. BMI and diet were both independent predictors for insulin resistance, and contributed 18 and 15 % of the variation in insulin resistance, respectively. In conclusion, Taiwanese vegetarians had lower glucose and insulin levels and higher insulin sensitivity than did the omnivores. Diet and lower BMI were partially responsible for the high insulin sensitivity observed in young Taiwanese vegetarians.\",\n \"title\": \"Taiwanese vegetarians have higher insulin sensitivity than omnivores.\"\n },\n {\n \"docid\": \"MED-1185\",\n \"text\": \"Endogenous sulfite is generated as a consequence of the body's normal processing of sulfur-containing amino acids. Sulfites occur as a consequence of fermentation and also occur naturally in a number of foods and beverages. As food additives, sulfiting agents were first used in 1664 and approved in the United States as long ago as the 1800s. With such long experience with their use, it is easy to understand why these substances have been regarded as safe. They are currently used for a variety of preservative properties, including controlling microbial growth, preventing browning and spoilage, and bleaching some foods. It is estimated that up to 500,000 (< .05% of the population) sulfite-sensitive individuals live in the United States. Sulfite sensitivity occurs most often in asthmatic adults--predominantly women; it is uncommonly reported in preschool children. Adverse reactions to sulfites in nonasthmatics are extremely rare. Asthmatics who are steroid-dependent or who have a higher degree of airway hyperreactivity may be at greater risk of experiencing a reaction to sulfite-containing foods. Even within this limited population, sulfite sensitivity reactions vary widely, ranging from no reaction to severe. The majority of reactions are mild. These manifestations may include dermatologic, respiratory, or gastrointestinal signs and symptoms. Severe nonspecific signs and symptoms occur less commonly. Broncho-constriction is the most common sensitivity response in asthmatics. The precise mechanisms of the sensitivity responses have not been completely elucidated. Inhalation of sulfur dioxide (SO2) generated in the stomach following ingestion of sulfite-containing foods or beverages, a deficiency in a mitochondrial enzyme, and an IgE-mediated immune response have all been implicated.(ABSTRACT TRUNCATED AT 250 WORDS)\",\n \"title\": \"Sulfite sensitivity: significance in human health.\"\n },\n {\n \"docid\": \"MED-1614\",\n \"text\": \"AIM: To compare the insulin sensitivity indices between Chinese vegetarians and omnivores. METHODS: The study included 36 healthy volunteers (vegetarian, n=19; omnivore, n=17) who had normal fasting plasma glucose levels. Each participant completed an insulin suppression test. We compared steady-state plasma glucose (SSPG), fasting insulin, the homeostasis model assessment for insulin sensitivity (HOMA-IR and HOMA %S) and beta-cell function (HOMA %beta) between the groups. We also tested the correlation of SSPG with years on a vegetarian diet. RESULTS: The omnivore subjects were younger than the vegetarians (55.7+/-3.7 vs 58.6+/-3.6 year of age, P=0.022). There was no difference between the two groups in sex, blood pressure, renal function tests and lipid profiles. The omnivores had higher serum uric acid levels than vegetarians (5.25+/-0.84 vs 4.54+/-0.75 mg/dl, P=0.011). The results of the indices were different between omnivores and vegetarians (SSPG (mean+/-s.d.) 105.4+/-10.2 vs 80.3+/-11.3 mg/dl, P<0.001; fasting insulin, 4.06+/-0.77 vs 3.02+/-1.19 microU/ml, P=0.004; HOMA-IR, 6.75+/-1.31 vs 4.78+/-2.07, P=0.002; HOMA %S, 159.2+/-31.7 vs 264.3+/-171.7%, P=0.018) except insulin secretion index, HOMA %beta (65.6+/-18.0 vs 58.6+/-14.8%, P=0.208). We found a clear linear relation between years on a vegetarian diet and SSPG (r=-0.541, P=0.017). CONCLUSIONS: The vegetarians were more insulin sensitive than the omnivore counterparts. The degree of insulin sensitivity appeared to be correlated with years on a vegetarian diet.\",\n \"title\": \"Insulin sensitivity in Chinese ovo-lactovegetarians compared with omnivores.\"\n },\n {\n \"docid\": \"MED-3277\",\n \"text\": \"Methionine dependence is a metabolic defect that occurs in many human tumor cell lines but not normal in unestablished cell strains. Methionine-dependent tumor cell lines are unable to proliferate and arrest in the late S/G2 phase of the cell cycle when methionine is replaced by its immediate precursor homocysteine in the culture medium (MET-HCY+ medium). However, it is not known whether methionine dependence occurs in fresh patient tumors as it does in cell lines. In order to determine whether methionine dependence occurs in fresh patient tumors as well as whether methionine dependence occurs in fresh patient tumors as well as in cell lines we took advantage of the technique of sponge-gel-supported histoculture to grow tumors directly from surgery. We then measured nuclear DNA content by image analysis to determine the cell cycle position in MET-HCY+ compared to MET+HCY- medium in 21 human patient tumors. Human tumor cell lines found to be methionine dependent by cell count were used as positive controls and were found to have marked reduction of cells in G1 compared to total cells in the cell cycle in MET-HCY+ medium with respect to the G1: total cell ratio in MET+HCY- medium. Therefore late cell cycle arrest was used as a marker of methionine dependence for histocultured patient tumors. We found that 5 human tumors of 21, including tumors of the colon, breast, ovary, prostate, and a melanoma, were methionine dependent based on cell cycle analysis. These data on fresh human tumors indicate that methionine dependence may frequently occur in the cancer patient population. Implications for potential therapy based on methionine dependence are discussed.\",\n \"title\": \"Expression of the biochemical defect of methionine dependence in fresh patient tumors in primary histoculture.\"\n },\n {\n \"docid\": \"MED-2276\",\n \"text\": \"A limited number of studies have demonstrated that some modulators of inflammation can be altered by the consumption of sweet cherries. We have taken a proteomics approach to determine the effects of dietary cherries on targeted gene expression. The purpose was then to determine changes caused by cherry consumption in the plasma concentrations of multiple biomarkers for several chronic inflammatory diseases in healthy humans with modestly elevated C-reactive protein (CRP; range, 1-14 mg/L; mean, 3.5 mg/L; normal, <1.0 mg/L). Eighteen men and women (45-61 y) supplemented their diets with Bing sweet cherries (280 g/d) for 28 d. Fasting blood samples were taken before the start of consuming the cherries (study d 7), 28 d after the initiation of cherry supplementation (d 35), and 28 d after the discontinuation (d 63). Of the 89 biomarkers assessed, cherry consumption for 28 d altered concentrations of 9, did not change those of 67, and the other 13 were below the detection limits. Cherry consumption decreased (P < 0.05) plasma concentrations of extracellular newly identified ligand for the receptor for advanced glycation end products (29.0%), CRP (20.1%), ferritin (20.3%), plasminogen activator inhibitor-1 (19.9%), endothelin-1 (13.7%), epidermal growth factor (13.2%), and IL-18 (8.1%) and increased that of IL-1 receptor antagonist (27.9%) compared with corresponding values on study d 7. The ferritin concentration continued to decrease between d 35 and 63 and it was significantly lower on d 63 than on d 7. Because the participants in this study were healthy, no clinical pathology end points were measured. However, results from the present study demonstrate that cherry consumption selectively reduced several biomarkers associated with inflammatory diseases.\",\n \"title\": \"Sweet bing cherries lower circulating concentrations of markers for chronic inflammatory diseases in healthy humans.\"\n },\n {\n \"docid\": \"MED-1223\",\n \"text\": \"OBJECTIVE: To assess the life history consequences of cow milk consumption at different stages in early life (prenatal to adolescence), especially with regard to linear growth and age at menarche and the role of insulin-like growth factor I (IGF-I) in mediating a relationship among milk, growth and development, and long-term biological outcomes. METHODS: United States National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2004 and review of existing literature. RESULTS: The literature tends to support milk's role in enhancing growth early in life (prior to age 5 years), but there is less support for this relationship during middle childhood. Milk has been associated with early menarche and with acceleration of linear growth in adolescence. NHANES data show a positive relationship between milk intake and linear growth in early childhood and adolescence, but not middle childhood, a period of relatively slow growth. IGF-I is a candidate bioactive molecule linking milk consumption to more rapid growth and development, although the mechanism by which it may exert such effects is unknown. CONCLUSIONS: Routine milk consumption is an evolutionarily novel dietary behavior that has the potential to alter human life history parameters, especially vis-à-vis linear growth, which in turn may have negative long-term biological consequences. Copyright © 2011 Wiley Periodicals, Inc.\",\n \"title\": \"Cow milk consumption, insulin-like growth factor-I, and human biology: a life history approach.\"\n },\n {\n \"docid\": \"MED-2368\",\n \"text\": \"BACKGROUND: Microparticles (MPs) with procoagulant activity are present in human atherosclerosis, but no detailed information is available on their composition. METHODS AND RESULTS: To obtain insights into the role of MPs in atherogenesis, MP proteins were identified by tandem mass spectrometry, metabolite profiles were determined by high-resolution nuclear magnetic resonance spectroscopy, and antibody reactivity was assessed against combinatorial antigen libraries. Plaque MPs expressed surface antigens consistent with their leukocyte origin, including major histocompatibility complex classes I and II, and induced a dose-dependent stimulatory effect on T-cell proliferation. Notably, taurine, the most abundant free organic acid in human neutrophils, which scavenges myeloperoxidase-catalyzed free radicals, was highly enriched in plaque MPs. Moreover, fluorescent labeling of proteins on the MP surface suggested immunoglobulins to be trapped inside, which was confirmed by flow cytometry analysis on permeabilized and nonpermeabilized plaque MPs. Colabeling for CD14 and IgG established that more than 90% of the IgG containing MPs were CD14(+), indicating a macrophage origin. Screening against an antigen library revealed that the immunologic profiles of antibodies in MPs were similar to those found in plaques but differed profoundly from antibodies in plasma and unexpectedly, showed strong reactions with oligosaccharide antigens, in particular blood group antigen A. CONCLUSIONS: This study provides the first evidence that immunoglobulins are present within MPs derived from plaque macrophages, that the portfolio of plaque antibodies is different from circulating antibodies in plasma, and that anticarbohydrate antibodies are retained in human atherosclerotic lesions.\",\n \"title\": \"Proteomics, metabolomics, and immunomics on microparticles derived from human atherosclerotic plaques.\"\n },\n {\n \"docid\": \"MED-2468\",\n \"text\": \"BACKGROUND AND METHODS: We estimated the prevalence of self-reported asthma in adult Indians and examined several risk factors influencing disease prevalence. Analysis is based on 99 574 women and 56 742 men aged 20–49 years included in India’s third National Family Health Survey, 2005–2006. Multiple logistic regression analysis was used to estimate the prevalence odds ratios for asthma, adjusting for various risk factors. RESULTS: The prevalence of self-reported asthma was 1.8% (95%CI 1.6–2.0) among men and 1.9% (95%CI 1.8–2.0) among women, with higher rates in rural than in urban areas and marked geographic differences. After adjustment for known asthma risk factors, women were 1.2 times more likely to have asthma than men. Daily/weekly consumption of milk/milk products, green leafy vegetables and fruits were associated with a lower asthma risk, whereas consumption of chicken/meat, a lower body mass index (BMI; <16 kg/m2, OR 2.08, 95%CI 1.73–2.50) as well as a higher BMI (>30 kg/m2, OR 1.67, 95%CI 1.36–2.06), current tobacco smoking (OR 1.30, 95%CI 1.12–1.50) and ever use of alcohol (OR 1.21, 95%CI 1.05–1.39) were associated with an increased asthma risk. CONCLUSIONS: There are wide regional variations in the prevalence of asthma in India. With the exception of the findings for BMI, however, most of the associations of asthma with the risk factors are relatively weak and account for only a small proportion of cases. RÉSUMÉ CONTEXTE ET MÉTHODES: Nous avons estimé la prévalence auto-rapportée de l’asthme chez les Indiens adultes et examiné plusieurs facteurs de risque influençant la prévalence de la maladie. L’analyse repose sur 99 574 femmes et 56 742 hommes âgés de 20 à 49 ans et inclus dans la troisième Enquête Nationale des Familles en Inde, 2005–2006. On a utilisé l’analyse de régression logistique multiple pour estimer les odds ratio de prévalence pour l’asthme, après ajustement pour divers facteurs de risque. RÉSULTATS: La prévalence auto-rapportée de l’asthme est de 1,8% (IC95% 1,6–2,0) parmi les hommes et de 1,9% (IC95% 1,8–2,0) parmi les femmes, les taux étant plus élevés dans les zones rurales que dans les zones urbaines, et les différences géographiques étant marquées. Après ajustement pour les facteurs de risque d’asthme connus, les femmes sont 1,2 fois plus susceptibles de souffrir de l’asthme que les hommes. La consommation quotidienne ou hebdomadaire de lait/produits laitiers, de légumes à feuilles vertes et de fruits est en association avec un risque plus faible d’asthme alors que la consommation de poulet ou de viande, un index de masse corporelle (BMI) plus bas (<16 kg/m2, OR 2,08 ; IC95% 1,73–2,50) ainsi qu’un BMI plus élevé (>30 kg/m2, OR 1,67 ; IC95% 1,36–2,06), le fait de fumer du tabac actuellement (OR 1,30 ; IC95% 1,12–1,50) et l’utilisation de l’alcool à un moment quelconque (OR 1,21 ; IC95% 1,05–1,39) sont en association avec un risque accru d’asthme. La prévalence de l’asthme en Inde varie largement selon les régions. Toutefois, à l’exception des observations sur le BMI, l’association de l’asthme avec les facteurs de risque est relativement faible et ne rend compte que d’une petite proportion des cas seulement. RESUMEN MARCO DE REFERENCIA Y MÉTODOS: Se calculó la prevalencia de asma autorreferida en los adultos en la India y se evaluaron varios factores de riesgo que influyen sobre la prevalencia de la enfermedad. El estudio se basó en las 99 574 mujeres y los 56 742 hombres de 20 a 49 años de edad que participaron en la tercera Encuesta Nacional sobre la Salud de la Familia en la India entre el 2005 y el 2006. Mediante un análisis de regresión logística multifactorial se calculó la prevalencia de asma y el cociente de posibilidades de padecerla, al corregir diversos factores de riesgo. RESULTADOS: La prevalencia de asma autorreferida fue 1,8% en los hombres (intervalo de confianza [IC] del 95% 1,6 a 2,0) y 1,9% en las mujeres (IC95% 1,8 a 2,0); se observaron tasas más altas en las zonas rurales que en las zonas urbanas y se presentaron diferencias geográficas considerables. Tras corregir en función de algunos factores de riesgo de padecer asma conocidos, las mujeres presentaron una probabilidad 1,2 veces superior a los hombres de sufrir la enfermedad. El consumo diario o semanal de leche o productos lácteos, hortalizas de hojas verdes y frutas se asoció con un menor riesgo de asma y el consumo de carne de pollo o de res, un bajo índice de masa corporal (<16 kg/m2; OR 2,08; IC95% 1,73 a 2,50) igual que un alto índice de masa corporal (>30 kg/m2; OR 1,67; IC95% 1,36 a 2,06), el tabaquismo actual (OR 1,30; IC95% 1,12 a 1,50) y el consumo de alcohol en algún momento de la vida (OR 1,21; IC95% 1,05 a 1,39) se asociaron con un mayor riesgo de padecer la enfermedad. CONCLUSIÓN: Existen amplias variaciones geográficas en la prevalencia de asma en la India. Sin embargo, con la excepción del índice de masa corporal, la mayor parte de las asociaciones del asma con los factores de riesgo fueron débiles y explican solo una pequeña proporción de los casos.\",\n \"title\": \"Prevalence and risk factors for self-reported asthma in an adult Indian population: a cross-sectional survey\"\n },\n {\n \"docid\": \"MED-3283\",\n \"text\": \"Available information indicates that long-lived mammals have low rates of reactive oxygen species (ROS) generation and oxidative damage at their mitochondria. On the other hand, many studies have consistently shown that dietary restriction (DR) in rodents also decreases mitochondrial ROS (mtROS) production and oxidative damage to mitochondrial DNA and proteins. It has been observed that protein restriction also decreases mtROS generation and oxidative stress in rat liver, whereas neither carbohydrate nor lipid restriction change these parameters. This is interesting because protein restriction also increases maximum longevity in rodents (although to a lower extent than DR) and is a much more practicable intervention for humans than DR, whereas neither carbohydrate nor lipid restriction seem to change rodent longevity. Moreover, it has been found that isocaloric methionine restriction also decreases mtROS generation and oxidative stress in rodent tissues, and this manipulation also increases maximum longevity in rats and mice. In addition, excessive dietary methionine also increases mtROS generation in rat liver. These studies suggest that the reduced intake of dietary methionine can be responsible for the decrease in mitochondrial ROS generation and the ensuing oxidative damage that occurs during DR, as well as for part of the increase in maximum longevity induced by this dietary manipulation. In addition, the mean intake of proteins (and thus methionine) of Western human populations is much higher than needed. Therefore, decreasing such levels to the recommended ones has a great potential to lower tissue oxidative stress and to increase healthy life span in humans while avoiding the possible undesirable effects of DR diets.\",\n \"title\": \"Lowered methionine ingestion as responsible for the decrease in rodent mitochondrial oxidative stress in protein and dietary restriction possible i...\"\n },\n {\n \"docid\": \"MED-1250\",\n \"text\": \"The effect of plant and animal protein on blood lipid levels was investigated in eight healthy normolipidemic men aged 18 to 27 yr. All subjects were fed both plant and animal protein diets in a cross-over design. Each diet was consumed for a 21-day period. Proteins from commonly used plant sources made up the plant protein diet. Beef protein was substituted for 55% of the plant proteins in the animal protein diet. Fasting venous blood samples were collected at the beginning of the study and at 7-day intervals throughout the 42-day study. Serum was analyzed for total cholesterol and triglycerides. Plasma low-density and high-density lipoprotein cholesterol were determined. There were not any statistically significant differences in mean serum total cholesterol or mean plasma low-density lipoprotein cholesterol when subjects consumed the diets. Mean plasma high-density lipoprotein cholesterol levels were significantly (p less than 0.05) elevated at the end of the 21-day period when the animal protein diet was consumed (48 +/- 3 mg/dl) compared to the period when the plant protein diet was fed (42 +/- 2 mg/dl). Mean serum triglyceride values were significantly (p less than 0.05) increased at day 7 of the plant protein diet period (136 +/- 19 mg/dl) compared to the same time period when the animal protein diet was consumed (84 +/- 12 mg/dl). The results of the study indicated that the ingestion of a diet in which 55% of the protein was supplied by beef protein was not associated with a hypercholesterolemic effect in healthy normolipidemic young men.\",\n \"title\": \"A comparison of the effect of diets containing beef protein and plant proteins on blood lipids of healthy young men.\"\n },\n {\n \"docid\": \"MED-1229\",\n \"text\": \"Milk has been recognized to represent a functionally active nutrient system promoting neonatal growth of mammals. Cell growth is regulated by the nutrient-sensitive kinase mechanistic target of rapamycin complex 1 (mTORC1). There is still a lack of information on the mechanisms of mTORC1 up-regulation by milk consumption. This review presents milk as a materno-neonatal relay system functioning by transfer of preferential amino acids, which increase plasma levels of glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), insulin, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) for mTORC1 activation. Importantly, milk exosomes, which regularly contain microRNA-21, most likely represent a genetic transfection system enhancing mTORC1-driven metabolic processes. Whereas human breast milk is the ideal food for infants allowing appropriate postnatal growth and species-specific metabolic programming, persistent high milk signaling during adolescence and adulthood by continued cow´s milk consumption may promote mTORC1-driven diseases of civilization.\",\n \"title\": \"Milk is not just food but most likely a genetic transfection system activating mTORC1 signaling for postnatal growth\"\n },\n {\n \"docid\": \"MED-2472\",\n \"text\": \"Thirty-five patients who had suffered from bronchial asthma for an average of 12 yr, all receiving long-term medication, 20 including cortisone, were subject to therapy with vegan food for 1 yr. In almost all cases, medication was withdrawn or drastically reduced. There was a significant decrease in asthma symptoms. Twenty-four patients (69%) fulfilled the treatment. Of these, 71% reported improvement at 4 months and 92% at 1 yr. There was a significant improvement in a number of clinical variables; for example, vital capacity, forced expiratory volume at one sec and physical working capacity, as well as a significant change in various biochemical indices as haptoglobin, IgM, IgE, cholesterol, and triglycerides in blood. Selected patients, with a fear of side-effects of medication, who are interested in alternative health care, might get well and replace conventional medication with this regimen.\",\n \"title\": \"Vegan regimen with reduced medication in the treatment of bronchial asthma.\"\n },\n {\n \"docid\": \"MED-3311\",\n \"text\": \"OBJECTIVES: We studied mortality in two separate cohorts of workers in abattoirs (N=4996) and meat processing plants (N=3642) belonging to a meatcutters' union, because they were exposed to viruses that cause cancer in food animals, and also to chemical carcinogens at work. METHODS: Standardized mortality ratios (SMRs) and proportional mortality ratios (PMRs) were estimated for each cohort as a whole and in subgroups defined by race and sex, using the US general population mortality rates for comparison. Study subjects were followed up from January 1950 to December 2006, during which time over 60% of them died. RESULTS: An excess of deaths from cancers of the base of the tongue, esophagus, lung, skin, bone and bladder, lymphoid leukemia, and benign tumors of the thyroid and other endocrine glands, and possibly Hodgkin's disease, was observed in abattoir and meat processing workers. Significantly lower SMRs were recorded for cancer of the thymus, mediastinum, pleura, etc., breast cancer, and non-Hodgkin's lymphoma. CONCLUSION: This study confirms the excess occurrence of cancer in workers in abattoirs and meat processing plants, butchers, and meatcutters, previously reported in this cohort and other similar cohorts worldwide. Large nested case-control studies are now needed to examine which specific occupational and non-occupational exposures are responsible for the excess. There is now sufficient evidence for steps to be taken to protect workers from carcinogenic exposures at the workplace. There are also serious implications for the general population which may also be exposed to some of these viruses. Copyright © 2011 Elsevier Ltd. All rights reserved.\",\n \"title\": \"Cancer mortality in workers employed in cattle, pigs, and sheep slaughtering and processing plants.\"\n },\n {\n \"docid\": \"MED-2357\",\n \"text\": \"Patients with cancer have circulating heterophile antibodies that agglutinate animal red cells via recognition of the mammalian cell surface sialic acid N-glycolylneuraminic acid (Neu5Gc), which was long considered an oncofetal antigen in humans. However, humans are genetically deficient in Neu5Gc production and instead metabolically accumulate Neu5Gc from dietary sources, particularly red meats and milk products. Moreover, mice with a human-like defect showed no alternate pathway for Neu5Gc synthesis and even normal humans express anti-Neu5Gc antibodies. We show here that human tumors accumulate Neu5Gc that is covalently attached to multiple classes of glycans. The paradox of human tumor Neu5Gc accumulation in the face of circulating anti-Neu5Gc antibodies was hypothesized to be due to facilitation of tumor progression by the resulting low-grade chronic inflammation. Indeed, murine tumors expressing human-like levels of Neu5Gc show accelerated growth in syngeneic mice with a human-like Neu5Gc deficiency, coincident with the induction of anti-Neu5Gc antibodies and increased infiltration of inflammatory cells. Transfer of polyclonal monospecific syngeneic mouse anti-Neu5Gc serum also enhanced growth of transplanted syngeneic tumors bearing human-like levels of Neu5Gc, with tumors showing evidence for antibody deposition, enhanced angiogenesis and chronic inflammation. These effects were suppressed by a cyclooxygenase-2 inhibitor, a drug type known to reduce human carcinoma risk. Finally, affinity-purified human anti-Neu5Gc antibodies also accelerate growth of Neu5Gc-containing tumors in Neu5Gc-deficient mice. Taken together, the data suggest that the human propensity to develop diet-related carcinomas is contributed to by local chronic inflammation, resulting from interaction of metabolically-accumulated dietary Neu5Gc with circulating anti-Neu5Gc antibodies.\",\n \"title\": \"Evidence for a human-specific mechanism for diet and antibody-mediated inflammation in carcinoma progression\"\n },\n {\n \"docid\": \"MED-3282\",\n \"text\": \"BACKGROUND AND AIMS: The mechanisms of cancer cell growth and metastasis are still not entirely understood, especially from the viewpoint of chemical reactions in tumours. Glycolytic metabolism is markedly accelerated in cancer cells, causing the accumulation of glucose (a reducing sugar) and methionine (an amino acid), which can non-enzymatically react and form carcinogenic substances. There is speculation that this reaction produces gaseous sulfur-containing compounds in tumour tissue. The aims of this study were to clarify the products in tumour and to investigate their effect on tumour proliferation. METHODS: Products formed in the reaction between glucose and methionine or its metabolites were analysed in vitro using gas chromatography. Flatus samples from patients with colon cancer and exhaled air samples from patients with lung cancer were analysed using near-edge x-ray fine adsorption structure spectroscopy and compared with those from healthy individuals. The tumour proliferation rates of mice into which HT29 human colon cancer cells had been implanted were compared with those of mice in which the cancer cells were surrounded by sodium hyaluronate gel to prevent diffusion of gaseous material into the healthy cells. RESULTS: Gaseous sulfur-containing compounds such as methanethiol and hydrogen sulfide were produced when glucose was allowed to react with methionine or its metabolites homocysteine or cysteine. Near-edge x-ray fine adsorption structure spectroscopy showed that the concentrations of sulfur-containing compounds in the samples of flatus from patients with colon cancer and in the samples of exhaled air from patients with lung cancer were significantly higher than in those from healthy individuals. Animal experiments showed that preventing the diffusion of sulfur-containing compounds had a pronounced antitumour effect. CONCLUSIONS: Gaseous sulfur-containing compounds are the main products in tumours and preventing the diffusion of these compounds reduces the tumour proliferation rate, which suggests the possibility of a new approach to cancer treatment.\",\n \"title\": \"Generation of gaseous sulfur-containing compounds in tumour tissue and suppression of gas diffusion as an antitumour treatment.\"\n },\n {\n \"docid\": \"MED-3356\",\n \"text\": \"OBJECTIVE: This study examined changes in desires to eat high-fat and low-fat foods across an obesity treatment program. The hypotheses under examination were (1) preferences for low-fat foods would increase across time and (2) preferences for high-fat foods would decrease across time. DESIGN: Single-group, prospective examination of desires to eat 48 foods, categorized according to fat content, before and after the 16-week treatment program. SETTING: University clinic, Memphis, Tennessee. PARTICIPANTS: 118 obese (mean weight = 194.4 lbs) women (mean age = 45.24 years) participating in an obesity treatment program. INTERVENTION: A 16-week cognitive-behavioral program for obesity. VARIABLES MEASURED: Desires to eat 48 foods varying in fat content and whether or not participants actually ate these foods. ANALYSIS: Analysis of variance, multiple regression, and paired t tests. RESULTS: The results indicate that during the program, preferences for low-fat foods increased, whereas preferences for high-fat foods decreased. These changes mirrored the changes in consumption of both low-fat and high-fat foods. CONCLUSIONS AND IMPLICATIONS: Within a behavioral economic perspective, the reinforcement value of low-fat foods may increase following a low-fat dietary intervention, whereas the reinforcing properties of high-fat foods may decline. This is desirable as low-fat foods hold many advantages over high-fat foods in terms of weight maintenance.\",\n \"title\": \"Desire to eat high- and low-fat foods following a low-fat dietary intervention.\"\n },\n {\n \"docid\": \"MED-2512\",\n \"text\": \"Ageing is a challenge for any living organism and human longevity is a complex phenotype. With increasing life expectancy, maintaining long-term health, functionality and well-being during ageing has become an essential goal. To increase our understanding of how ageing works, it may be advantageous to analyze the phenotype of centenarians, perhaps one of the best examples of successful ageing. Healthy ageing involves the interaction between genes, the environment, and lifestyle factors, particularly diet. Besides evaluating specific gene-environment interactions in relation to exceptional longevity, it is important to focus attention on modifiable lifestyle factors such as diet and nutrition to achieve extension of health span. Furthermore, a better understanding of human longevity may assist in the design of strategies to extend the duration of optimal human health. In this article we briefly discuss relevant topics on ageing and longevity with particular focus on dietary patterns of centenarians and nutrient-sensing pathways that have a pivotal role in the regulation of life span. Finally, we also discuss the potential role of Nrf2 system in the pro-ageing signaling emphasizing its phytohormetic activation.\",\n \"title\": \"Extending healthy ageing: nutrient sensitive pathway and centenarian population\"\n },\n {\n \"docid\": \"MED-3931\",\n \"text\": \"Although a plant-based diet can provide some benefits in Parkinson's disease (PD), no study to date has evaluated the effectiveness of a plant-food diet in the management of the disease. In this pilot study, we compared the effect of a plant-food menu (PFD) and of a omnivorous menu on motor performance of 25 PD patients, 12 in the intervention group (PDi) and 13 in the control group (PDc). After 4 weeks, the PDi group showed a significant reduction (Mann-Whitney test) in the Unified Parkinson's Disease Rating Scale, total score (47.67 vs. 74.46, P = 0.008) and sub-score III motor performances (25.42 vs. 46.46, P = 0.001), and the modified Hoehn and Yahr Staging Scale (1.96 vs. 3.15, P = 0.005). These data suggest that PFD may be useful in the management of PD patients by improving their motor performances. Additional studies are needed in order to confirm these preliminary results.\",\n \"title\": \"Pilot dietary study with normoproteic protein-redistributed plant-food diet and motor performance in patients with Parkinson's disease.\"\n },\n {\n \"docid\": \"MED-4433\",\n \"text\": \"BACKGROUND: The role of zoonotic biological agents in human cancer occurrence has been little studied. Humans are commonly exposed to viruses that naturally infect and cause cancer in food animals such as poultry that constitute part of the biological environment. It is not known if these viruses cause cancer in humans. OBJECTIVE: To study cancer mortality in the largest cohort to date, of 20,132 workers in poultry slaughtering and processing plants, a group with the highest human exposures to these viruses. METHODS: Mortality in poultry workers was compared with that in the US general population through the estimation of standardized mortality ratios. RESULTS: Significantly increased risks were observed in the cohort as a whole or in subgroups, for several cancer sites, viz: cancers of the buccal cavity and pharynx; pancreas; trachea/bronchus/lung; brain; cervix; lymphoid leukemia; monocytic leukemia; and tumors of the hemopoietic and lymphatic systems. Elevated SMRs that were not statistically significant were observed for cancers of the liver, nasopharynx, myelofibrosis, and myeloma. New sites observed to be significantly in excess in this study were cancers of the cervix and penis. CONCLUSION: This large study provides evidence that a human group with high exposure to poultry oncogenic viruses has increased risk of dying from several cancers. Other occupational carcinogenic exposures could be of importance in explaining some of the findings, such as fumes from wrapping machines. These findings may have implications for public health amongst persons in the general population who may also be exposed to these viruses. What is needed now are epidemiologic studies that can demonstrate whether the excess of specific cancers can be attributed to specific occupational exposures while adequately controlling for other potential occupational and non-occupational carcinogenic exposures. Copyright 2010 Elsevier Inc. All rights reserved.\",\n \"title\": \"Cancer mortality in poultry slaughtering/processing plant workers belonging to a union pension fund.\"\n },\n {\n \"docid\": \"MED-2474\",\n \"text\": \"This ISAAC Phase Three synthesis provides summarised information on the main findings of the study, regional tables and figures related to the prevalence and severity of current symptoms of asthma, rhinoconjunctivitis and eczema in the main regions of the world. The large number of surveyed children (≈1,200,000), the large number of centres (233) and countries (98) that participated in ISAAC Phase Three makes this study the most comprehensive survey of these diseases ever undertaken. Globally, the prevalence for current asthma, rhinoconjunctivitis and eczema in the 13-14-year age group was 14.1%, 14.6% and 7.3%, respectively. In the 6-7-year age group the prevalence for current asthma, rhinoconjunctivitis and eczema was 11.7%, 8.5% and 7.9%, respectively. The study shows a wide variability in the prevalence and severity of asthma, rhinoconjunctivitis and eczema which occurs not just between regions and countries but between centres in the same country and centres in the same city. This study definitively establishes that the prevalence of those diseases can be very high in non-affluent centres with low socioeconomic conditions. The large variability also suggests a crucial role of local environment characteristics to determine the differences in prevalence between one place and another. Thus, ISAAC Phase Three has provided a large body of epidemiological information on asthma, rhinoconjunctivitis and eczema in childhood from contrasting environments which is expected to yield new clues about the aetiology of those conditions and reasons for their marked global variability. Copyright © 2012 SEICAP. Published by Elsevier Espana. All rights reserved.\",\n \"title\": \"The International Study of Asthma and Allergies in Childhood (ISAAC) Phase Three: a global synthesis.\"\n },\n {\n \"docid\": \"MED-2823\",\n \"text\": \"Curcumin, the yellow pigment from the rhizoma of Curcuma longa, is a widely studied phytochemical which has a variety of biological activities: anti-inflammatory and anti-oxidative. In this review we discuss the biological mechanisms and possible clinical effects of curcumin treatment on cancer therapy, and neurodegenerative diseases such as Alzheimer's Disease, with particular attention to the cell death processes induced by curcumin. Since oxidative stress and inflammation are major determinants of the aging process, we also argue that curcumin can have a more general effect that slows down the rate of aging. Finally, the effects of curcumin can be described as xenohormetic, since it activates a sort of stress response in mammalian cells.\",\n \"title\": \"Curcumin in Cell Death Processes: A Challenge for CAM of Age-Related Pathologies\"\n },\n {\n \"docid\": \"MED-3295\",\n \"text\": \"Background Few studies have investigated mortality in seafood workers worldwide, and no such study has been conducted in the United States. The objective of this study was to investigate mortality in American seafood workers. Methods The study population was derived from 4 states and consisted of 4116 subjects who worked mainly in seafood processing plants. They were followed up from 1966 to 2003. Standardized mortality ratios (SMRs) and proportional mortality ratios (PMRs) were estimated, using the US general population for comparison. Results About 45% of the cohort was born after 1949. A total of 788 deaths were recorded; 53% of the decedents were female, and 88% were white. The SMRs for stomach cancer and disorders of the thyroid gland in the cohort as a whole were 2.1 (95% confidence interval [CI], 1.1–3.8) and 6.1 (95% CI 1.3–18.0), respectively. The SMRs for breast cancer, and occlusion/stenosis of the pre-cerebral/cerebral arteries in the cohort as a whole were 0.5 (95% CI, 0.3–0.9) and 0.5 (95% CI, 0.2–0.8), respectively. The SMR for ischemic heart disease in white females was 0.8 (95% CI, 0.6–0.9). Conclusions This cohort had excess deaths from stomach cancer and disorders of the thyroid gland, and deficit of deaths from breast cancer, stroke and ischemic heart disease. The significance of these findings is unknown, especially as less than 20% of the cohort were deceased. Nevertheless, the cohort is unique and important, and further follow-up may shed more light on mortality patterns in this occupational group.\",\n \"title\": \"Cancer and Noncancer Mortality Among American Seafood Workers\"\n },\n {\n \"docid\": \"MED-3321\",\n \"text\": \"Avian leukosis/sarcoma viruses (ALSV) infect and cause cancers in chickens. Poultry workers are exposed to ALSV and other infectious agents in the workplace. This study examines if industrial hygiene assessment of antibody levels in poultry workers can identify risky job tasks at the higher exposure risk to an infectious agent, i.e., ALSV. We compared ALSV antibody levels in poultry workers and control subjects. Occupational and demographical factors were examined for an association with the exposure risk in poultry workers. We found that the antibody levels were significantly higher in poultry workers than in control subjects. Job category and age together were significantly associated with the antibody levels in workers. Certain job tasks were identified with significantly higher antibody levels as compared to others, implying that recommendations should be made to protect workers at these jobs. The findings of this study indicate that the measurement of antibody levels in workers can be useful for industrial hygiene assessment of exposure to infectious agents.\",\n \"title\": \"Occupational exposure assessment using antibody levels: exposure to avian leukosis/sarcoma viruses in the poultry industry.\"\n },\n {\n \"docid\": \"MED-3232\",\n \"text\": \"High dietary acid load (DAL) may be detrimental to bone mineral density (BMD). The objectives of the study were to: 1) evaluate the cross-sectional relation between DAL and BMD; 2) determine whether calcium intake modifies this association. Men (n=1218) and women (n=907) ≥60y were included from the National Health and Nutrition Examination Survey 2005–2008. Nutrient intake from 2–24h recalls was used to calculate net endogenous acid production (NEAP) and potential renal acid load (PRAL) (mEq/d). PRAL was calculated from dietary calcium (PRALdiet) and diet + supplemental calcium (PRALtotal). Tests for linear trend in adjusted mean BMD of the hip and lumbar spine were performed across energy adjusted NEAP and PRAL quartiles. Modification by calcium intake (dietary or total) above or below 800 mg/d was assessed by interaction terms. Overall, mean age was 69 ± 0.3y. Among women, there was no association between NEAP and BMD. PRALdiet was positively associated with proximal femur BMD (p trend=0.04). No associations were observed with PRALtotal at any BMD site (P-range: 0.38–0.82). Among men, no significant associations were observed of BMD with NEAP or PRAL. However, an interaction between PRALdiet and calcium intake was observed with proximal femur BMD (p=0.08). An inverse association between PRALdiet and proximal femur BMD was detected among men <800 mg/d dietary calcium (p=0.02); and no associations ≥800 mg/d (p=0.98). A significant interaction with PRALtotal was not observed. In conclusion, when supplemental calcium is considered, there is no association between DAL and BMD among adults. Men with low dietary calcium showed an inverse relation with PRAL at the proximal femur; in women no interaction was observed. This study highlights the importance of calcium intakes in counteracting the adverse effect of DAL on bone health. Further research should determine the relation between DAL and change in BMD with very low calcium intake.\",\n \"title\": \"Dietary acid load is associated with lower bone mineral density in men with low intake of dietary calcium\"\n },\n {\n \"docid\": \"MED-4198\",\n \"text\": \"In this study, silkworm moth (Bombyx mori L.) larvae were regarded as an animal protein source for astronauts in the bioregenerative life support system during long-term deep space exploration in the future. They were fed with mulberry and stem lettuce leaves during the first three instars and the last two instars, respectively. In addition, this kind of environmental approach, which utilised inedible biomass of plants to produce animal protein of high quality, can likewise be applied terrestrially to provide food for people living in extreme environments and/or impoverished agro-ecosystems, such as in polar regions, isolated military bases, ships, submarines, etc. Respiration characteristics of the larvae during development under two main physiological conditions, namely eating and not-eating of leaves, were studied. Nutrient compositions of silkworm powder (SP), ground and freeze-dried silkworms on the 3rd day of the 5th instar larvae, including protein, fat, vitamins, minerals and fatty acids, were measured using international standard methods. Silkworms' respiration rates, measured when larvae were eating mulberry leaves, were higher than those of similar larvae that hadn't eaten such leaves. There was a significant difference between silkworms fed on mulberry leaves and those fed on stem lettuce in the 4th and 5th instars (P<0.01). Amounts of CO2 exhaled by the silkworms under the two physiological regimes differed from each other (P<0.01). There was also a significant difference between the amount of O2 inhaled when the insects were under the two physiological statuses (P<0.01). Moreover, silkworms' respiration quotient under the eating regime was larger than when under the not-eating regime. The SP was found to be rich in protein and amino acids in total; 12 essential vitamins, nine minerals and twelve fatty acids were detected. Moreover, 359 kcal could be generated per 100 gram of SP (dry weight).\",\n \"title\": \"Insect food for astronauts: gas exchange in silkworms fed on mulberry and lettuce and the nutritional value of these insects for human consumption ...\"\n },\n {\n \"docid\": \"MED-2446\",\n \"text\": \"BACKGROUND: Allergic diseases have risen in prevalence over recent decades. The aetiology remains unclear but is likely to be a result of changing lifestyle and/or environment. A reduction in antioxidant intake, consequent to reduced intake of fresh fruits and vegetables, has been suggested as a possible cause. OBJECTIVE: To investigate whether dietary antioxidant intake at age 5 was related to atopy at 5 and 8 years of age amongst children in an unselected birth cohort. METHODS: Children were followed from birth. Parents completed a validated respiratory questionnaire and children were skin prick tested at 5 and 8 years of age. Serum IgE levels were measured at age 5. At age 5, antioxidant intake was assessed using a semi-quantitative food frequency questionnaire (FFQ). A nutrient analysis program computed nutrient intake, and frequency counts of foods high in the antioxidant vitamins A, C and E were assessed. RESULTS: Eight hundred and sixty-one children completed both the respiratory and FFQ. Beta-carotene intake was associated with reduced risk of allergic sensitization at age 5 [0.80 (0.68-0.93)] and 8 [0.81 (0.70-0.94)]. In addition, beta-carotene intake was negatively associated with total IgE levels (P = 0.002). Vitamin E intake was associated with an increased risk of allergic sensitization [1.19 (1.02-1.39)], only at age 5. There was no association between antioxidant intakes and wheeze or eczema. CONCLUSION: Increased beta-carotene intake was associated with a reduced risk of allergic sensitization and lower IgE levels, in 5- and 8-year-old children. Dietary antioxidants may play a role in the development of allergic sensitization.\",\n \"title\": \"Dietary antioxidant intake, allergic sensitization and allergic diseases in young children.\"\n },\n {\n \"docid\": \"MED-2201\",\n \"text\": \"Measuring food prices per gram, rather than per calorie, is one way to make healthful vegetables appear less expensive. However, a better measure of affordability would take the nutrient content of vegetables into account. This study, based on analyses of US Department of Agriculture datasets, aimed to identify which vegetables, including juices and soups, provided the most nutrients per unit cost. Nutrient density was measured using the Nutrient Rich Foods (NRF) index, based on nine nutrients to encourage: protein; fiber; vitamins A, C, and E; calcium; iron; magnesium; and potassium; and on three nutrients to limit: saturated fat, added sugar, and sodium. Food cost in dollars was calculated per 100 g, per 100 kcal, per serving, and per nutrient content. One-way analyses of variance with post hoc tests were used to determine statistical significance. Results showed that tomato juices and tomato soups, dark green leafy and nonleafy vegetables, and deep yellow vegetables, including sweet potatoes, had the highest NRF scores overall. Highest NRF scores per dollar were obtained for sweet potatoes, white potatoes, tomato juices and tomato soups, carrots, and broccoli. Tomato sauces, raw tomatoes, and potato chips were eaten more frequently than were many other vegetables that were both more affordable and more nutrient-rich. These new measures of affordable nutrition can help foodservice and health professionals identify those vegetables that provide the highest nutrient density per unit cost. Processed vegetables, including soups and juices, can contribute to the quality and the affordability of the diet. Copyright © 2013 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.\",\n \"title\": \"New metrics of affordable nutrition: which vegetables provide most nutrients for least cost?\"\n },\n {\n \"docid\": \"MED-3306\",\n \"text\": \"OBJECTIVES: Occupation as a farmer has been associated with increased risks of haematological cancers in adults. This study aimed to examine whether farm exposures in childhood contribute to these risks, by using parental occupation in farming as a proxy for growing up on a farm. METHODS: New Zealand death records (1998-2003) of persons aged 35-85 were extracted (n=114 289). For 82.3% usual occupation and the occupation of at least one of the parents could be coded (n=94 054). Unconditional logistic regression analyses included 3119 haematological cancer deaths (cases) and 90 935 deaths from other causes (controls). ORs for farming and growing up on a farm were adjusted for each other, year of birth, age at death, socio-economic status, Māori ethnicity, immigration status and sex. RESULTS: Growing up on a livestock farm was positively associated with haematological cancer (OR 1.22, 95% CI 1.05 to 1.41), particularly for poultry farms (OR 2.99, 95% CI 1.44 to 6.21), while growing up on a crop farm was not (OR 0.81, 95% CI 0.64 to 1.03). Crop farming in adulthood was associated with an increased haematological cancer risk (OR 1.49, 95% CI 1.13 to 1.96), while livestock farming was not (OR 0.80, 95% CI 0.63 to 1.00), except for beef cattle farming (OR 2.99, 95% CI 1.28 to 7.00). These results did not change appreciably when different control groups with different causes of death were used. CONCLUSIONS: These results could suggest a role for early life biological exposures in the development of haematological cancers.\",\n \"title\": \"Farming, growing up on a farm, and haematological cancer mortality.\"\n },\n {\n \"docid\": \"MED-3231\",\n \"text\": \"This review looks at the role of an alkaline diet in health. Pubmed was searched looking for articles on pH, potential renal acid loads, bone health, muscle, growth hormone, back pain, vitamin D and chemotherapy. Many books written in the lay literature on the alkaline diet were also reviewed and evaluated in light of the published medical literature. There may be some value in considering an alkaline diet in reducing morbidity and mortality from chronic diseases and further studies are warranted in this area of medicine.\",\n \"title\": \"The Alkaline Diet: Is There Evidence That an Alkaline pH Diet Benefits Health?\"\n },\n {\n \"docid\": \"MED-3452\",\n \"text\": \"Vitamins have traditionally been considered as food components that are required in the normal diet to prevent deficiencies. However, a newer concept of the function of vitamins in nutrition has taken them beyond simply prevention of deficiency symptoms. This concept considers that many vitamins, when taken in relatively large doses, have important functions beyond preventing deficiencies. Linus Pauling was instrumental in putting forward this concept, particularly for vitamin C. Thus, relatively high intakes of vitamins, and in particular vitamins C and E which are antioxidants, are considered to be healthy for the human population. This may be true in some special situations such as, for instance, the prevention of Alzheimer's disease progression. However, recent epidemiological evidence has not supported the claim that antioxidant vitamins increase well-being and prolong life span. In fact, vitamin supplementation may be even detrimental and reduce life span. A new concept that we would like to put forward is that nutrients up-regulate the endogenous antioxidant defences. This is particularly true in the case of phytoestrogens for example, which bind to oestrogen receptors and eventually up-regulate the expression of antioxidant genes. In this review we discuss the pros and cons of antioxidant vitamin supplementation and also the possibility that the ingestion of some nutrients may be very effective in increasing antioxidant defences by up-regulating the activity of antioxidant enzymes which are normally present in the cell.\",\n \"title\": \"Fostering antioxidant defences: up-regulation of antioxidant genes or antioxidant supplementation?\"\n },\n {\n \"docid\": \"MED-4950\",\n \"text\": \"Previously used standards for the diagnosis of precocious puberty in girls no longer appear to be appropriate in the USA, in that a significant number of girls are being seen in paediatricians' offices with breast budding before 8 years of age. The timing of menarche, however, has changed little over the past few decades. Early maturing girls are more likely to become obese in adolescence and adulthood than normal or late maturing girls. Early maturing white girls are heavier at the onset of puberty, but this is not the case for African-American girls or boys of either race. Boys and girls with premature pubarche may be more hyperinsulinaemic than normal children, and girls with premature pubarche more likely to develop functional ovarian and adrenal hyperandrogenism. Early menarche is preceded by prepubertal hyperinsulinaemia. It is proposed that pubertal onset, although not necessarily the tempo of puberty, is influenced by hyperinsulinaemia and insulin resistance. If this hypothesis is correct, insulin resistance may be more prevalent in US children than previously recognized. An advance in timing of onset of puberty has not been noted in other countries, although it is likely that this phenomenon may become more prevalent as other countries adopt a more American lifestyle and diet.\",\n \"title\": \"The pubertal timing controversy in the USA, and a review of possible causative factors for the advance in timing of onset of puberty.\"\n },\n {\n \"docid\": \"MED-2501\",\n \"text\": \"Amino acids play fundamental roles in the cell both as the building blocks of new proteins and as metabolic precursors. To adapt to their limitation during periods of protein starvation, multiple adaptive mechanisms have evolved, including a rapid cessation of new protein synthesis, an increase in amino acid biosynthesis and transport, and autophagy. Here, we discuss what we currently know about how amino acid limitation is sensed, and how this sensing might be transmitted to mTORC1 to regulate protein synthesis and autophagy. Copyright © 2012 Elsevier Ltd. All rights reserved.\",\n \"title\": \"Amino acid sensing and regulation of mTORC1.\"\n },\n {\n \"docid\": \"MED-1097\",\n \"text\": \"Moses Maimonides (1135-1204), physician and philosopher, was the greatest Jewish thinker of the Middle Ages. Faced with a life of persecution, exile, and tragedy, Maimonides overcame obstacles to become the leading physician in his era, a clinician whose skills were sought across continents. Despite long days caring for patients, Maimonides wrote extensively about both medicine and philosophy. His medical works span all topics of clinical medicine and reflect rational thinking and an understanding of the relationship between mind and body. Well known for his philosophical writings, such as The Guide for the Perplexed, Maimonides codified Jewish law and revolutionized Jewish thinking. This review of his life and achievements provides insight into the world of a remarkable 12th-century physician and may offer valuable lessons for physicians today.\",\n \"title\": \"Moses Maimonides: medieval physician and scholar.\"\n },\n {\n \"docid\": \"MED-4722\",\n \"text\": \"BACKGROUND: There has been a resurgence of interest in the controversial relation between dietary protein and bone health. OBJECTIVE: This article reports on the first systematic review and meta-analysis of the relation between protein and bone health in healthy human adults. DESIGN: The MEDLINE (January 1966 to September 2007) and EMBASE (1974 to July 2008) databases were electronically searched for all relevant studies of healthy adults; studies of calcium excretion or calcium balance were excluded. RESULTS: In cross-sectional surveys, all pooled r values for the relation between protein intake and bone mineral density (BMD) or bone mineral content at the main clinically relevant sites were significant and positive; protein intake explained 1-2% of BMD. A meta-analysis of randomized placebo-controlled trials indicated a significant positive influence of all protein supplementation on lumbar spine BMD but showed no association with relative risk of hip fractures. No significant effects were identified for soy protein or milk basic protein on lumbar spine BMD. CONCLUSIONS: A small positive effect of protein supplementation on lumbar spine BMD in randomized placebo-controlled trials supports the positive association between protein intake and bone health found in cross-sectional surveys. However, these results were not supported by cohort study findings for hip fracture risk. Any effects found were small and had 95% CIs that were close to zero. Therefore, there is a small benefit of protein on bone health, but the benefit may not necessarily translate into reduced fracture risk in the long term.\",\n \"title\": \"Dietary protein and bone health: a systematic review and meta-analysis.\"\n },\n {\n \"docid\": \"MED-3272\",\n \"text\": \"Objective Early detection and early treatment are of vital importance to the successful treatment of various cancers. The development of a novel screening method that is as economical and non-invasive as the faecal occult blood test (FOBT) for early detection of colorectal cancer (CRC) is needed. A study was undertaken using canine scent detection to determine whether odour material can become an effective tool in CRC screening. Design Exhaled breath and watery stool samples were obtained from patients with CRC and from healthy controls prior to colonoscopy. Each test group consisted of one sample from a patient with CRC and four control samples from volunteers without cancer. These five samples were randomly and separately placed into five boxes. A Labrador retriever specially trained in scent detection of cancer and a handler cooperated in the tests. The dog first smelled a standard breath sample from a patient with CRC, then smelled each sample station and sat down in front of the station in which a cancer scent was detected. Results 33 and 37 groups of breath and watery stool samples, respectively, were tested. Among patients with CRC and controls, the sensitivity of canine scent detection of breath samples compared with conventional diagnosis by colonoscopy was 0.91 and the specificity was 0.99. The sensitivity of canine scent detection of stool samples was 0.97 and the specificity was 0.99. The accuracy of canine scent detection was high even for early cancer. Canine scent detection was not confounded by current smoking, benign colorectal disease or inflammatory disease. Conclusions This study shows that a specific cancer scent does indeed exist and that cancer-specific chemical compounds may be circulating throughout the body. These odour materials may become effective tools in CRC screening. In the future, studies designed to identify cancer-specific volatile organic compounds will be important for the development of new methods for early detection of CRC.\",\n \"title\": \"Colorectal cancer screening with odour material by canine scent detection\"\n },\n {\n \"docid\": \"MED-4038\",\n \"text\": \"We previously reported an association between prenatal exposure to airborne PAH and lower birth weight, birth length and head circumference. The main goal of the present analysis was to assess the possible impact of co-exposure to PAH-containing of barbecued meat consumed during pregnancy on birth outcomes. The birth cohort consisted of 432 pregnant women who gave birth at term (>36 weeks of gestation). Only non-smoking women with singleton pregnancies, 18-35 years of age, and who were free from chronic diseases such as diabetes and hypertension were included in the study. Detailed information on diet over pregnancy was collected through interviews and the measurement of exposure to airborne PAHs was carried out by personal air monitoring during the second trimester of pregnancy. The effect of barbecued meat consumption on birth outcomes (birthweight, length and head circumference at birth) was adjusted in multiple linear regression models for potential confounding factors such as prenatal exposure to airborne PAHs, child’s sex, gestational age, parity, size of mother (maternal prepregnancy weight, weight gain in pregnancy) and prenatal environmental tobacco smoke (ETS). The multivariable regression model showed a significant deficit in birthweight associated with barbecued meat consumption in pregnancy (coeff = −106.0 g; 95%CI: −293.3, −35.8); The effect of exposure to airborne PAHs was about the same magnitude order (coeff. = −164.6 g; 95%CI: −172.3, − 34.7). Combined effect of both sources of exposure amounted to birth weight deficit of 214.3 g (95%CI: −419.0, − 9.6). Regression models performed for birth length and head circumference showed similar trends but the estimated effects were of borderline significance level. As the intake of barbecued meat did not affect the duration of pregnancy, the reduced birthweight could not have been mediated by shortened gestation period. In conclusion, the study results provided epidemiologic evidence that prenatal PAH exposure from diet including grilled meat might be hazardous for fetal development.\",\n \"title\": \"IMPACT OF BARBECUED MEAT CONSUMED IN PREGNANCY ON BIRTH OUTCOMES ACCOUNTING FOR PERSONAL PRENATAL EXPOSURE TO AIRBORNE POLYCYCLIC AROMATIC HYDROCARBONS. BIRTH COHORT STUDY IN POLAND\"\n },\n {\n \"docid\": \"MED-2589\",\n \"text\": \"BACKGROUND: Determination of the effects of dietary modification and hyperlipidemic medications in the elderly (> sixty-five years of age) patient has not been significantly investigated to date despite knowledge that elevated cholesterol (TC) and triglyceride (TG) levels increase the risk of coronary artery disease (CAD). METHODS: Twenty-seven individuals were placed into one of three treatment groups and longitudinally followed up to examine the effects of diet and hyperlipidemic medications on TC and TG levels. Group 1 (n = 14) received neither dietary nor drug therapy. Group 2 (n = 9) received dietary counseling without concomitant hyperlipidemic medications. Subjects in group 3 (n = 4) underwent dietary instruction for six months and hyperlipidemic medication(s) for eighteen months. RESULTS: Subjects in group 1 demonstrated a statistical increase in TC (P < or = 0.001) during the study. Patients in groups 2 (P < or = 0.001) and 3 (P < or = 0.05) demonstrated statistical improvement in TC reduction during dietary counseling. The effect on TC was blunted in group 3 after dietary counseling was discontinued. Reductions in TG levels were significant (P < or = 0.001) only for patients in group 2. CONCLUSION: Elderly individuals were able to significantly reduce both TC and TG levels by dietary modification alone. Minimal improvement was seen with the addition of hyperlipidemic medications.\",\n \"title\": \"Treating hyperlipidemia in the elderly.\"\n },\n {\n \"docid\": \"MED-4211\",\n \"text\": \"Circulating levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) have each been associated with premenopausal breast cancer risks. We analyzed data from a cross-sectional study of 261 premenopausal Japanese women aged 20-54 yr with adequate nutritional status to evaluate the relationships between concentrations of IGF-1 and IGFBP-3 in serum and dietary intakes of soy, fats and other nutrients. Diet was assessed by a semiquantitative food frequency questionnaire. There was no significant correlation between soy product as well as soy isoflavone intake and serum IGF-1 or IGFBP-3 levels after controlling for age, total energy, percent body fat, and education level. Total fat intake was significantly inversely correlated with serum IGFBP-3 level (r = -0.13, P = 0.04). The correlations of saturated and monounsaturated fats with serum IGFBP-3 were of borderline significance (r = -0.12, P = 0.06 and r = -0.11, P = 0.07, respectively).\",\n \"title\": \"Dietary soy and fats in relation to serum insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 levels in premenopausal Jap...\"\n },\n {\n \"docid\": \"MED-3316\",\n \"text\": \"BACKGROUND: Between November, 2006, and May, 2008, a subacute neurological syndrome affected workers from two swine abattoirs in Minnesota and Indiana who had occupational exposure to aerosolised porcine brain. We aimed to describe the pathogenic and immunological characteristics of this illness. METHODS: All patients from two abattoirs who presented or were referred to the Mayo Clinic (Rochester, MN, USA) with neurological symptoms were included. We recorded details of exposure to aerosolised brain tissue and did comprehensive neurological, laboratory, neuroimaging, electrophysiological, pathological, and autoimmune serological assessments. Healthy controls were recruited from the community and from workers at the plant in Minnesota. FINDINGS: 24 patients were identified (21 from Minnesota, three from Indiana). The shortest duration from first exposure to symptom onset was 4 weeks. No infectious agent that could trigger disease was identified. All patients developed polyradiculoneuropathy, which was usually sensory predominant and painful. Two patients had initial CNS manifestations: transverse myelitis and meningoencephalitis. Nerve conduction studies localised abnormalities to the most proximal and distal nerve segments. Quantitative sensory and autonomic testing revealed involvement of large and small sensory fibres and sweat fibres. MRI showed prominent abnormalities of roots and ganglia. Nerve biopsies identified mild demyelination, axonal degeneration, and perivascular inflammation. Protein concentrations were high in the CSF of 18 (86%) of 21 patients. Sera from all patients and 29 (34%) of 85 unaffected workplace controls (but none of 178 community controls) had a distinctive neural-reactive IgG; 75% of patients' sera contained an IgG specific to myelin basic protein. Seropositivity correlated directly with exposure risk in patients and controls. 17 patients required immunomodulatory therapies, six improved spontaneously, and one was lost to follow-up after exposure stopped. INTERPRETATION: The neurological disorder described is autoimmune in origin and is related to occupational exposure to multiple aerosolised porcine brain tissue antigens. The pattern of nerve involvement suggests vulnerability of nerve roots and terminals where the blood-nerve barrier is most permeable. FUNDING: Mayo Clinic Foundation; Minnesota Department of Health; Centers for Disease Control and Prevention. Copyright 2010 Elsevier Ltd. All rights reserved.\",\n \"title\": \"An outbreak of neurological autoimmunity with polyradiculoneuropathy in workers exposed to aerosolised porcine neural tissue: a descriptive study.\"\n },\n {\n \"docid\": \"MED-2507\",\n \"text\": \"Increased plasma levels of adiponectin, metformin therapy of diabetes, rapamycin administration in transplant patients, and lifelong consumption of low-protein plant-based diets have all been linked to decreased risk for various cancers. These benefits may be mediated, at least in part, by down-regulated activity of the mTORC1 complex, a key regulator of protein translation. By boosting the effective availability of the translation initiator eIF4E, mTORC1 activity promotes the translation of a number of \\\"weak\\\" mRNAs that code for proteins, often up-regulated in cancer, that promote cellular proliferation, invasiveness, and angiogenesis, and that abet cancer promotion and chemoresistance by opposing apoptosis. Measures which inhibit eIF4E activity, either directly or indirectly, may have utility not only for cancer prevention, but also for the treatment of many cancers in which eIF4E drives malignancy. Since eIF4E is overexpressed in many cancers, strategies which target eIF4E directly--some of which are now being assessed clinically--may have the broadest efficacy in this regard. Many of the \\\"weak\\\" mRNAs coding for proteins that promote malignant behavior or chemoresistance are regulated transcriptionally by NF-kappaB and/or Stat3, which are active in a high proportion of cancers; thus, regimens concurrently targeting eIF4E, NF-kappaB, and Stat3 may suppress these proteins at both the transcriptional and translational levels, potentially achieving a very marked reduction in their expression. Copyright © 2011 Elsevier Ltd. All rights reserved.\",\n \"title\": \"mTORC1 activity as a determinant of cancer risk--rationalizing the cancer-preventive effects of adiponectin, metformin, rapamycin, and low-protein ...\"\n },\n {\n \"docid\": \"MED-2509\",\n \"text\": \"DR (dietary restriction), or reduced food intake without malnutrition, is associated with extended longevity, improved metabolic fitness and increased stress resistance in a wide range of organisms. DR is often referred to as calorie restriction, implying that reduced energy intake is responsible for its widespread and evolutionarily conserved benefits. However, recent data indicate dietary amino acid restriction as a key mediator of DR benefits. In fruitflies, an imbalance in essential amino acid intake is thought to underlie longevity benefits of DR. In mammals, reduced dietary protein or essential amino acid intake can extend longevity, improve metabolic fitness and increase stress resistance. In the present paper we review two evolutionarily conserved signal transduction pathways responsible for sensing amino acid levels. The eIF2α (eukaryotic initiation factor 2α) kinase GCN2 (general amino acid control non-derepressible 2) senses the absence of one or more amino acids by virtue of direct binding to uncharged cognate tRNAs. The presence of certain amino acids, such as leucine, permits activation of the master growth regulating kinase TOR (target of rapamycin). These two signal transduction pathways react to amino acid deprivation by inhibiting general protein translation while at the same time increasing translation of specific mRNAs involved in restoring homoeostasis. Together, these pathways may contribute to the regulation of longevity, metabolic fitness and stress resistance.\",\n \"title\": \"Amino acid sensing in dietary-restriction-mediated longevity: roles of signal-transducing kinases GCN2 and TOR\"\n },\n {\n \"docid\": \"MED-2288\",\n \"text\": \"In recent years there has been considerable interest in the benefits of high-protein diets. This study determined current usual intake of protein in America. Using the most recent data from the National Health and Nutrition Examination Survey, 2003-2004, usual protein intake for Americans aged 2+ years was estimated. Usual protein intake was calculated on a grams per day, grams per kilogram ideal body weight, and a percentage of calories basis. Protein intake averaged 56 +/- 14 g/d in young children, increased to a high of approximately 91 +/- 22 g/d in adults aged 19-30 y, and decreased to approximately 66 +/- 17 g/d in the elderly. The percentage of the male population who consumed less than the estimated average requirement was very low. Our estimates indicated that 7.7% of adolescent females and 7.2-8.6% of older adult women reported consuming protein levels below their estimated average requirement. The median intake of protein on a percentage of calories basis ranged from 13.4% in children aged 4-8 y to 16.0% in men aged 51-70 y. Even the 95th percentile of protein intake did not approach the highest acceptable macronutrient distribution range of 35% for an age/sex group. The highest 95th percentile of protein intake was 20.8% of calories in men aged 51-70 y. Given the demonstrated benefits of higher protein intake on weight management, sarcopenia, and other physiologic functions, efforts should be undertaken to ensure that Americans consume the recommended amount of protein (17-21% of calories as expected from MyPyramid food patterns).\",\n \"title\": \"Current protein intake in America: analysis of the National Health and Nutrition Examination Survey, 2003-2004.\"\n },\n {\n \"docid\": \"MED-2645\",\n \"text\": \"The development of the male reproductive ducts and external genitalia in vertebrates is dependent on elevated androgen concentrations during embryonic development and the period of postnatal growth. We have observed that a population of juvenile alligators living on Lake Apopka exhibit significantly smaller penis size (24% average decrease) and lower plasma concentrations of testosterone (70% lower concentrations) when compared to animals of similar size on Lake Woodruff. In addition to smaller phalli, no relationship exists between plasma testosterone concentrations and penile size in males from Lake Apopka, whereas a positive relationship exists for males from Lake Woodruff. The alligators on Lake Apopka are known to have elevated concentrations of the antiandrogenic DDT breakdown product p.p'-DDE stored in their fat. We suggest a number of hypotheses that could explain the modification in the phenotype of the juvenile male living in Lake Apopka. These modifications in phenotype include a smaller penis size, lower plasma androgen concentrations, and lack of responsiveness of the penis to the plasma androgens present.\",\n \"title\": \"Reduction in penis size and plasma testosterone concentrations in juvenile alligators living in a contaminated environment.\"\n },\n {\n \"docid\": \"MED-3956\",\n \"text\": \"Early onset of puberty may confer adverse health consequences. Thus, modifiable factors influencing the timing of puberty are of public health interest. Childhood overweight as a factor in the earlier onset of menarche has been supported by prospective evidence; nonetheless, its overall contribution may have been overemphasized, since secular trends toward a younger age at menarche have not been a universal finding during the recent obesity epidemic. Current observational studies suggest notable associations between dietary intakes and pubertal timing beyond contributions to an energy imbalance: children with the highest intakes of vegetable protein or animal protein experience pubertal onset up to 7 months later or 7 months earlier, respectively. Furthermore, girls with high isoflavone intakes may experience the onset of breast development and peak height velocity approximately 7-8 months later. These effect sizes are on the order of those observed for potentially neuroactive steroid hormones. Thus, dietary patterns characterized by higher intakes of vegetable protein and isoflavones and lower intakes of animal protein may contribute to a lower risk of breast cancer or a lower total mortality. © 2012 International Life Sciences Institute.\",\n \"title\": \"Beyond overweight: nutrition as an important lifestyle factor influencing timing of puberty.\"\n },\n {\n \"docid\": \"MED-3148\",\n \"text\": \"We examined the resting metabolic rate (RMR) and sympathetic nervous system activity of young male vegetarians (n = 17) and nonvegetarians (n = 40). Subjects were characterized for RMR by indirect calorimetry, norepinephrine kinetics from infusions of tritiated norepinephrine, energy and macronutrient intake from a 3-day food diary, and body composition by underwater weighing. Vegetarians reported a greater relative intake of carbohydrates (62% +/- 5% v 51% +/- 6%, P < .01) and a lower relative intake of fat (25% +/- 5% v 33% +/- 6%, P < .01) than nonvegetarians, whereas no differences were observed in daily energy intake, body composition, or maximal aerobic capacity (VO2max) between groups. Vegetarians exhibited an 11% higher absolute RMR (1.29 +/- 0.15 v 1.16 +/- 0.13 kcal/min, P < .01), a higher plasma concentration of norepinephrine (216 +/- 33 v 165 +/- 18 pg/mL, P < .01), and a greater norepinephrine appearance rate (0.50 +/- 0.08 v 0.36 +/- 0.09 micrograms/min, P < .01) than nonvegetarians. After statistically controlling for differences in relative amounts of carbohydrate and fat in the diet and for norepinephrine concentrations, no significant differences in adjusted RMR between vegetarians and nonvegetarians were noted. These results suggest that the higher RMR observed in young male vegetarians is partially mediated by differences in dietary macronutrient composition and increased sympathetic nervous system activity.\",\n \"title\": \"Sympathetic nervous system activity and resting metabolic rate in vegetarians.\"\n },\n {\n \"docid\": \"MED-1615\",\n \"text\": \"Hyperinsulinemia, hypertension, hypertriglyceridemia and obesity are independent risk factors for coronary artery disease and are often found in the same person. This study investigated the effects of an intensive, 3-week, dietary and exercise program on these risk factors. The group was divided into diabetic patients (non-insulin-dependent diabetes mellitus [NIDDM], n = 13), insulin-resistant persons (n = 29) and those with normal insulin, less than or equal to 10 microU/ml (n = 30). The normal groups had very small but statistically significant decreases in all of the risk factors. The patients with NIDDM had the greatest decreases. Insulin was reduced from 40 +/- 15 to 27 +/- 11 microU/ml, blood pressure from 142 +/- 9/83 +/- 3 to 132 +/- 6/71 +/- 3 mm Hg, triglycerides from 353 +/- 76 to 196 +/- 31 mg/dl and body mass index from 31.1 +/- 4.0 to 29.7 +/- 3.7 kg/m2. Although there was a significant weight loss for the group with NIDDM, resulting in the decrease in body mass index, 8 of 9 patients who were initially overweight were still overweight at the end of the program, and 5 of the 8 were still obese (body mass index greater than 30 kg/m2), indicating that normalization of body weight is not a requisite for a reduction or normalization of other risk factors. Insulin was reduced from 18.2 +/- 1.8 to 11.6 +/- 1.2 microU/ml in the insulin-resistant group, with 17 of the 29 subjects achieving normal fasting insulin (less than 10 microU/ml).(ABSTRACT TRUNCATED AT 250 WORDS)\",\n \"title\": \"Role of diet and exercise in the management of hyperinsulinemia and associated atherosclerotic risk factors.\"\n },\n {\n \"docid\": \"MED-3308\",\n \"text\": \"An occupational health survey conducted in a workshop in which asbestos cement was used showed initial atmospheric asbestos levels ranging from 1.9 to 27.5 fibres per millilitre of air. Radiological changes suggestive of asbestos-related pleural disease were found in 2 workers (2.5%), while 3 (3.8%) had borderline features of asbestosis. The survey confirmed that uncontrolled and hazardous use of asbestos continues in industry despite public awareness of its dangers and the Asbestos Regulations of 1987.\",\n \"title\": \"Third wave of asbestos-related disease from secondary use of asbestos. A case report from industry.\"\n },\n {\n \"docid\": \"MED-1224\",\n \"text\": \"In adults, dietary protein seems to induce weight loss and dairy proteins may be insulinotropic. However, the effect of milk proteins in adolescents is unclear. The objective was to test whether milk and milk proteins reduce body weight, waist circumference, homeostatic model assessment, plasma insulin, and insulin secretion estimated as the plasma C-peptide concentration in overweight adolescents. Overweight adolescents (n = 203) aged 12-15 y with a BMI of 25.4 ± 2.3 kg/m(2) (mean ± SD) were randomized to 1 L/d of skim milk, whey, casein, or water for 12 wk. All milk drinks contained 35 g protein/L. Before randomization, a subgroup of adolescents (n = 32) was studied for 12 wk before the intervention began as a pretest control group. The effects of the milk-based test drinks were compared with baseline (wk 0), the water group, and the pretest control group. Diet and physical activity were registered. Outcomes were BMI-for-age Z-scores (BAZs), waist circumference, plasma insulin, homeostatic model assessment, and plasma C-peptide. We found no change in BAZ in the pretest control and water groups, whereas it was greater at 12 wk in the skim milk, whey, and casein groups compared with baseline and with the water and pretest control groups. The plasma C-peptide concentration increased from baseline to wk 12 in the whey and casein groups and increments were greater than in the pretest control (P < 0.02). There were no significant changes in plasma C-peptide in the skim milk or water group. These data suggest that high intakes of skim milk, whey, and casein increase BAZs in overweight adolescents and that whey and casein increase insulin secretion. Whether the effect on body weight is primary or secondary to the increased insulin secretion remains to be elucidated.\",\n \"title\": \"Skim milk, whey, and casein increase body weight and whey and casein increase the plasma C-peptide concentration in overweight adolescents.\"\n },\n {\n \"docid\": \"MED-3288\",\n \"text\": \"In the fall of 2007, the Minnesota Department of Health was notified of 11 cases of an unexplained neurological illness, all linked to a pork processing plant, Quality Pork Processors, Inc., in Austin, MN. The cluster of workers had been experiencing similar symptoms, including fatigue, pain, numbness, and tingling in their extremities as well as weakness. The symptoms were described as more sensory than motor, and all patients had evidence of polyradiculoneuropathy with signs of nerve root irritation. An epidemiological investigation revealed that the only commonality between cases was their exposure to a pork brain extraction procedure involving compressed air. As relatives of the cases remained asymptomatic and all cultures for known pathogens were negative, the etiology of the syndrome seemed not to be infectious. Clinically, the syndrome was most akin to chronic inflammatory demyelinating polyneuropathy. Laboratory tests corroborated the clinical findings, revealing inflammation of peripheral nerves and nerve roots; however, these cases also had features clinically distinct from chronic inflammatory demyelinating polyneuropathy as well as laboratory testing revealing a novel immunoglobulin G immunostaining pattern. This suggested that the observed inflammation was the result of 1 or more unidentified antigens. This syndrome was ultimately dubbed progressive inflammatory neuropathy and was theorized to be an autoimmune reaction to aerosolized porcine neural tissue. Since the investigation's outset, 18 cases of progressive inflammatory neuropathy have been identified at the Minnesota pork processing plant, with 5 similar cases at an Indiana plant and 1 case at a Nebraskan plant. The plants in which cases have been identified have since stopped the use of compressed air in removing pork brains. All cases have stabilized or improved, with some requiring immunosuppressive and analgesic treatment. The study of progressive inflammatory neuropathy is ongoing, and the details of this investigation highlight the value of epidemiological principles in the identification and containment of outbreaks while researchers attempt to uncover the unique pathophysiology and potential etiology of the illness. Mt Sinai J Med 76:442-447, 2009. (c) 2009 Mount Sinai School of Medicine.\",\n \"title\": \"Outbreak of progressive inflammatory neuropathy following exposure to aerosolized porcine neural tissue.\"\n },\n {\n \"docid\": \"MED-5185\",\n \"text\": \"There is some evidence that dietary factors may modify the risk of squamous cell carcinoma (SCC) of the skin, but the association between food intake and SCC has not been evaluated prospectively. We examined the association between food intake and SCC incidence among 1,056 randomly selected adults living in an Australian sub-tropical community. Measurement-error corrected estimates of intake in 15 food groups were defined from a validated food frequency questionnaire in 1992. Associations with SCC risk were assessed using Poisson and negative binomial regression to the persons affected and tumour counts, respectively, based on incident, histologically confirmed tumours occurring between 1992 and 2002. After multivariable adjustment, none of the food groups was significantly associated with SCC risk. Stratified analysis in participants with a past history of skin cancer showed a decreased risk of SCC tumours for high intakes of green leafy vegetables (RR = 0.45, 95% CI = 0.22-0.91; p for trend = 0.02) and an increased risk for high intake of unmodified dairy products (RR = 2.53, 95% CI: 1.15-5.54; p for trend = 0.03). Food intake was not associated with SCC risk in persons who had no past history of skin cancer. These findings suggest that consumption of green leafy vegetables may help prevent development of subsequent SCCs of the skin among people with previous skin cancer and that consumption of unmodified dairy products, such as whole milk, cheese and yoghurt, may increase SCC risk in susceptible persons. Copyright 2006 Wiley-Liss, Inc.\",\n \"title\": \"Food intake and risk of squamous cell carcinoma of the skin in a community: the Nambour skin cancer cohort study.\"\n },\n {\n \"docid\": \"MED-4047\",\n \"text\": \"The total phenolic contents and antioxidant activities of garlics from California, Oregon, Washington, and New York were determined by Fourier transform infrared (FT-IR) spectroscopy (400-4000 cm(-1)). The total phenolic content was quantified [Folin-Ciocalteu assay (FC)] and three antioxidant activity assays, 2,2-diphenyl-picrylhydrazyl (DPPH) assay, Trolox equivalent antioxidant capacity (TEAC) assay, and ferric reducing antioxidant power (FRAP), were employed for reference measurements. Four independent partial least-squares regression (PLSR) models were constructed with spectra from 25 extracts and their corresponding FC, DPPH, TEAC, and FRAP with values for 20 additional extracts predicted (R > 0.95). The standard errors of calibration and standard error of cross-validation were <1.45 (TEAC), 0.36 (FRAP), and 0.33 μmol Trolox/g FW (DPPH) and 0.55 mg gallic acid/g FW (FC). Cluster and dendrogram analyses could segregate garlic grown at different locations. Hydroxyl and phenolic functional groups most closely correlated with garlic antioxidant activity.\",\n \"title\": \"Determination of total phenolic content and antioxidant activity of garlic (Allium sativum) and elephant garlic (Allium ampeloprasum) by attenuated...\"\n },\n {\n \"docid\": \"MED-3130\",\n \"text\": \"Although soy phytoestrogens have been postulated to exert a protective effect against breast cancer, the attendant mechanisms, in particular epigenetics underpinnings, have remained elusive. We investigated the putative effects on DNA methylation by two naturally occurring isoflavones, genistein and daidzein, in a study of the BRCA1 and BRCA2 oncosuppressor genes in breast cancer cell lines (MCF-7, MDA-MB 231, and MCF10a). A demethylant agent, the 5-azacytidine, and a methylant, the budesonide, were used as treatment controls. DNA methylation of BRCA1 and BRCA2 was investigated with methylated DNA immunoprecipitation coupled with PCR. In parallel, protein expression was determined by Western blot, immunohistochemistry, and confocal microscopy. Our results suggest that treatment with 18.5 μM Genistein or 78.5 μM Daidzein might reverse DNA hypermethylation and restore the expression of the oncosuppressor genes BRCA1 and BRCA2. 5-Azacitydine also enhanced the reexpression of these genes while budesonide had an opposite effect. To the best of our knowledge, these observations, while requiring replication, provide new evidence on potential epigenetic mechanisms by which genistein and daidzein might contribute to regulation of the BRCA1 and BRCA2. Future studies are warranted on whether the demethylating effect of genistein and daidzein is global or focused on select candidate genes.\",\n \"title\": \"Can soy phytoestrogens decrease DNA methylation in BRCA1 and BRCA2 oncosuppressor genes in breast cancer?\"\n },\n {\n \"docid\": \"MED-2204\",\n \"text\": \"The initial investigation of the nature of the proteins in the tuber of sweet potato (Ipomoea batatas Lam.) revealed a globulin-designated \\\"ipomoein,\\\" which was reported by Jones and Gersdorff, (1931). Later, \\\"ipomoein\\\" was renamed \\\"sporamin\\\" and was found to be a major storage protein that accounted for over 80% of the total protein in the tuberous root. To date, sporamin has been studied by a series of biochemical and molecular approaches. The first purification of sporamin into two major fractions, A and B, was successfully completed in 1985. Several characteristics of the protein, such as the diversification of the nucleotide sequences in the gene family, the protein structure, the biological functions of storage, defense, inhibitory activity and ROS scavenging, were identified. In the past decade, sporamin was classified as a Kunitz-type trypsin inhibitor, and its insect-resistance capability has been examined in transgenic tobacco and cauliflower plants, indicating the multiple functions of this protein has evolved to facilitate the growth and development of sweet potato. Sporamin is constitutively expressed in the tuberous root and is not normally expressed in the stem or leaves. However, this protein is expressed systemically in response to wounding and other abiotic stresses. These dual expression patterns at the transcriptional level revealed that the complex regulatory mechanism of sporamin was modulated by environmental stresses. The versatile functions of sporamin make this storage protein a good research model to study molecular evolution, regulatory mechanisms and physiological functions in plants. This review summarizes and discusses recent approaches and future perspectives in agricultural biotechnology. Copyright © 2012 Elsevier Inc. All rights reserved.\",\n \"title\": \"Multiple biological functions of sporamin related to stress tolerance in sweet potato (Ipomoea batatas Lam).\"\n },\n {\n \"docid\": \"MED-2657\",\n \"text\": \"BACKGROUND: Japanese cedar pollinosis, caused by the pollen of the Japanese cedar tree (Cryptomeria japonica), is the commonest seasonal allergic disease in Japan. A number of epidemiological surveys have been reported on Japanese cedar pollinosis, but it has never been assessed systematically or quantitatively. To confirm the increasing prevalence of Japanese cedar pollinosis and related factors, we conducted a meta-regression analysis on population-based surveys in Japan. METHODS: We searched for data from population-based surveys in which serological methods were used to test all participants. Weighted regression of logit-transformed prevalence and sensitization rates were used to evaluate the effects of the year of survey, age, and degree of urbanization. We also analyzed the relationship between prevalence and sensitization rate. RESULTS: Thirty-eight reports with 27 subgroups for prevalence and 134 subgroups for sensitization rate were selected from the literature published in the years between 1986 and 2000. The Japanese cedar pollen sensitization rate was found to be significantly correlated with the year of survey, age, and degree of urbanization (adjusted R(2) = 0.55). The coefficient for the correlation between the prevalence and the sensitization rate revealed a statistically significant correlation (Pearson's r = 0.70, p < 0.001). CONCLUSIONS: The prevalence of Japanese cedar pollinosis among adolescents was predicted to be 28.7% in metropolitan areas and 24.5% in the general population in urban areas in the year 2004, derived from the estimated sensitization rate and the relationship between sensitization rate and prevalence. The prevalence of Japanese cedar pollinosis increased 2.6-fold between 1980 and 2000, and the prevalence differed considerably according to age and degree of urbanization. Copyright (c) 2005 S. Karger AG, Basel\",\n \"title\": \"Increasing prevalence of Japanese cedar pollinosis: a meta-regression analysis.\"\n },\n {\n \"docid\": \"MED-3877\",\n \"text\": \"OBJECTIVES: Dietary factors may influence the prostate and have an impact on prostatic growth and disease. A small number of studies have suggested that flaxseed-supplemented, fat-restricted diets may thwart prostate cancer growth in both animals and humans. Unknown, however, is the potential effect of such a diet on benign prostatic epithelium. METHODS: We undertook a pilot study to explore whether a flaxseed-supplemented, fat-restricted diet affects the proliferation rates in benign epithelium. We also explored the effects on circulating levels of prostate-specific antigen (PSA), total testosterone, and cholesterol. Fifteen men who were scheduled to undergo repeat prostate biopsy were instructed to follow a low-fat (less than 20% kcal), flaxseed-supplemented (30 g/day) diet and were provided with a supply of flaxseed to last throughout the 6-month intervention period. The PSA, total testosterone, and cholesterol levels were determined at baseline and at 6 months of follow-up. Reports from the original and repeat biopsies were compared, and proliferation (MIB-1) rates were quantified in the benign prostatic epithelium. RESULTS: Statistically significant decreases in PSA (8.47 +/- 3.82 to 5.72 +/- 3.16 ng/mL; P = 0.0002) and cholesterol (241.1 +/- 30.8 to 213.3 +/- 51.2 mg/dL; P = 0.012) were observed. No statistically significant change was seen in total testosterone (434.5 +/- 143.6 to 428.3 +/- 92.5 ng/dL). Although 6-month repeat biopsies were not performed in 2 cases because of PSA normalization, of the 13 men who underwent repeat biopsy, the proliferation rates in the benign epithelium decreased significantly from 0.022 +/- 0.027 at baseline to 0.007 +/- 0.014 at 6 months of follow-up (P = 0.0168). CONCLUSIONS: These pilot data suggest that a flaxseed-supplemented, fat-restricted diet may affect the biology of the prostate and associated biomarkers. A randomized controlled trial is needed to determine whether flaxseed supplementation, a low-fat diet, or a combination of the two regimens may be of use in controlling overall prostatic growth.\",\n \"title\": \"Pilot study to explore effects of low-fat, flaxseed-supplemented diet on proliferation of benign prostatic epithelium and prostate-specific antigen.\"\n },\n {\n \"docid\": \"MED-5181\",\n \"text\": \"Recent evidence suggests overall dietary patterns, rather than specific dietary components, may be a better predictor of colorectal adenomas or cancers. Using cluster analysis, we aimed to assess the association between dietary patterns and colorectal adenomas and whether adjusting for total energy consumption prior to creating clusters affects this relation. Data from a case-control study of 725 individuals undergoing a colonoscopy were utilized. Cases (n = 203) had > or =1 adenoma on colonoscopy, and controls (n = 522) were those who had no adenomas. Dietary data were obtained from an FFQ. Daily intake for 18 different food groups was calculated. The values were transformed into Z-scores. Participants were first clustered without energy adjustment, then again based on their consumption per 1000 kcal (4187 kJ). There was no association between dietary patterns and colorectal adenomas without energy adjustment prior to creating dietary clusters, as clusters formed as a by-product of energy consumption. After adjusting for energy consumption, 3 distinct clusters emerged: 1) high fruit-low meat cluster; 2) high vegetable-moderate meat cluster; and 3) high meat cluster. After adjusting for potential confounders, the high vegetable-moderate meat cluster (odds ratio [OR] 2.17: [95% CI] 1.20-3.90) and high meat cluster (OR 1.70: [95% CI] 1.04-2.80) were at significantly increased odds of having had an adenoma compared with the high fruit-low meat cluster. A high-fruit, low-meat diet appears to be protective against colorectal adenomas compared with a dietary pattern of increased vegetable and meat consumption.\",\n \"title\": \"A diet high in fruits and low in meats reduces the risk of colorectal adenomas.\"\n },\n {\n \"docid\": \"MED-5183\",\n \"text\": \"Dietary phytochemical compounds, including isoflavones and isothiocyanates, may inhibit cancer development but have not yet been examined in prospective epidemiologic studies of ovarian cancer. The authors have investigated the association between consumption of these and other nutrients and ovarian cancer risk in a prospective cohort study. Among 97,275 eligible women in the California Teachers Study cohort who completed the baseline dietary assessment in 1995–1996, 280 women developed invasive or borderline ovarian cancer by December 31, 2003. Multivariable Cox proportional hazards regression, with age as the timescale, was used to estimate relative risks and 95% confidence intervals; all statistical tests were two sided. Intake of isoflavones was associated with lower risk of ovarian cancer. Compared with the risk for women who consumed less than 1 mg of total isoflavones per day, the relative risk of ovarian cancer associated with consumption of more than 3 mg/day was 0.56 (95% confidence interval: 0.33, 0.96). Intake of isothiocyanates or foods high in isothiocyanates was not associated with ovarian cancer risk, nor was intake of macronutrients, antioxidant vitamins, or other micronutrients. Although dietary consumption of isoflavones may be associated with decreased ovarian cancer risk, most dietary factors are unlikely to play a major role in ovarian cancer development.\",\n \"title\": \"Diet and Risk of Ovarian Cancer in the California Teachers Study Cohort\"\n },\n {\n \"docid\": \"MED-2464\",\n \"text\": \"BACKGROUND: In recent decades, children's diet quality has changed and asthma prevalence has increased, although it remains unclear if these events are associated. OBJECTIVE: To examine children's total and component diet quality and asthma and airway hyperresponsiveness (AHR), a proxy for asthma severity. METHODS: Food frequency questionnaires adapted from the Nurses' Health Study and supplemented with foods whose nutrients which have garnered interest of late in relation to asthma were administered. From these data, diet quality scores (total and component), based on the Youth Healthy Eating Index (YHEI adapted) were developed. Asthma assessments were performed by pediatric allergists and classified by atopic status: Allergic asthma (≥1 positive skin prick test to common allergens >3 mm compared to negative control) versus non-allergic asthma (negative skin prick test). AHR was assessed via the Cockcroft technique. Participants included 270 boys (30% with asthma) and 206 girls (33% with asthma) involved in the 1995 Manitoba Prospective Cohort Study nested case-control study. Logistic regression was used to examine associations between diet quality and asthma, and multinomial logistic regression was used to examine associations between diet quality and AHR. RESULTS: Four hundred seventy six children (56.7% boys) were seen at 12.6 ± 0.5 years. Asthma and AHR prevalence were 26.2 and 53.8%, respectively. In fully adjusted models, high vegetable intake was protective against allergic asthma (OR 0.49; 95% CI 0.29-0.84; P < 0.009) and moderate/severe AHR (OR 0.58; 0.37-0.91; P < 0.019). CONCLUSIONS: Vegetable intake is inversely associated with allergic asthma and moderate/severe AHR. Copyright © 2012 Wiley Periodicals, Inc.\",\n \"title\": \"Low vegetable intake is associated with allergic asthma and moderate-to-severe airway hyperresponsiveness.\"\n },\n {\n \"docid\": \"MED-4894\",\n \"text\": \"SUMMARY: This cross-sectional study showed that, although vegans had lower dietary calcium and protein intakes than omnivores, veganism did not have adverse effect on bone mineral density and did not alter body composition. INTRODUCTION: Whether a lifelong vegetarian diet has any negative effect on bone health is a contentious issue. We undertook this study to examine the association between lifelong vegetarian diet and bone mineral density and body composition in a group of postmenopausal women. METHODS: One hundred and five Mahayana Buddhist nuns and 105 omnivorous women (average age = 62, range = 50-85) were randomly sampled from monasteries in Ho Chi Minh City and invited to participate in the study. By religious rule, the nuns do not eat meat or seafood (i.e., vegans). Bone mineral density (BMD) at the lumbar spine (LS), femoral neck (FN), and whole body (WB) was measured by DXA (Hologic QDR 4500). Lean mass, fat mass, and percent fat mass were also obtained from the DXA whole body scan. Dietary calcium and protein intakes were estimated from a validated food frequency questionnaire. RESULTS: There was no significant difference between vegans and omnivores in LSBMD (0.74 +/- 0.14 vs. 0.77 +/- 0.14 g/cm(2); mean +/- SD; P = 0.18), FNBMD (0.62 +/- 0.11 vs. 0.63 +/- 0.11 g/cm(2); P = 0.35), WBBMD (0.88 +/- 0.11 vs. 0.90 +/- 0.12 g/cm(2); P = 0.31), lean mass (32 +/- 5 vs. 33 +/- 4 kg; P = 0.47), and fat mass (19 +/- 5 vs. 19 +/- 5 kg; P = 0.77) either before or after adjusting for age. The prevalence of osteoporosis (T scores < or = -2.5) at the femoral neck in vegans and omnivores was 17.1% and 14.3% (P = 0.57), respectively. The median intake of dietary calcium was lower in vegans compared to omnivores (330 +/- 205 vs. 682 +/- 417 mg/day, P < 0.001); however, there was no significant correlation between dietary calcium and BMD. Further analysis suggested that whole body BMD, but not lumbar spine or femoral neck BMD, was positively correlated with the ratio of animal protein to vegetable protein. CONCLUSION: These results suggest that, although vegans have much lower intakes of dietary calcium and protein than omnivores, veganism does not have adverse effect on bone mineral density and does not alter body composition.\",\n \"title\": \"Veganism, bone mineral density, and body composition: a study in Buddhist nuns.\"\n },\n {\n \"docid\": \"MED-3221\",\n \"text\": \"Background The finding reported in a previous paper - alkalization of urine facilitates uric acid excretion - is contradictory to what one might expect to occur: because food materials for the alkalization of urine contain fewer purine bodies than those for acidification, less uric acid in alkaline urine should have been excreted than in acid urine. To make clear what component of uric acid excretion mechanisms is responsible for this unexpected finding, we simultaneously collected data for the concentration of both creatinine and uric acid in serum as well as in urine, in order to calculate both uric acid and creatinine clearances. Methods Within the framework of the Japanese government’s health promotion program, we made recipes which consisted of protein-rich and less vegetable-fruit food materials for H + -load (acidic diet) and others composed of less protein and more vegetable-fruit rich food materials (alkaline diet). This is a crossover study within some limitations. Healthy female students, who had no medical problems at the regular physical examination provided by the university, were enrolled in this consecutive 5-day study for each test. From whole-day collected urine, total volume, pH, organic acid, creatinine, uric acid, titratable acid and all cations (Na+,K+,Ca2+,Mg2+,NH4+) and anions (Cl−,SO42−,PO4−) necessary for the estimation of acid–base balance were measured. In the early morning before breakfast of the 1st, 3rd and 5th experimental day, we sampled 5 mL of blood to estimate the creatinine and uric acid concentration in serum. Results and discussion Urine pH reached a steady state 3 days after switching from ordinary daily diets to specified regimens. The amount of acid generated ([SO42−] + organic acid − gut alkali)was linearly related with the excretion of acid (titratable acid + [NH4+] − [HCO3−]), indicating that H + in urine is generated by the metabolic degradation of food materials. Uric acid and excreted urine pH retained a linear relationship, as reported previously. Among the five factors which are associated with calculating clearances for both uric acid and creatinine, we identified a conspicuous difference between acidic and alkaline diets in the uric acid concentration in serum as well as in urine; uric acid in the serum was higher in the acidic group than in the alkaline group, while uric acid in the urine in the acidic group was lower than that in the alkaline group. These changes of uric acid in acidic urine and in serum were reflected in the reduction of its clearance. From these observations, it is considered that uric acid may be reabsorbed more actively in acidic urine than in alkaline urine. Conclusion We conclude that alkalization of urine by eating nutritionally well-designed alkaline -prone food is effective for removing uric acid from the body.\",\n \"title\": \"Effect of urine pH changed by dietary intervention on uric acid clearance mechanism of pH-dependent excretion of urinary uric acid\"\n },\n {\n \"docid\": \"MED-3786\",\n \"text\": \"This article describes the development of a series of choline- and betaine-controlled diets that were served to research subjects as part of an ongoing study of diet requirements in humans. These diets were developed based on the analysis of choline and betaine in individual foods. The calculated diets were compared with analyses of all foods combined into a single sample for each day. The laboratory analyses of choline and betaine in the whole-diet aliquots matched the estimated amounts in the diets that were calculated from the analyses of individual foods. These diets were adjusted for several levels of choline and betaine and were well accepted by research subjects who consumed them for a time period of up to 2 months. This article describes applications of this diet for use in clinical research on methyl-group requirements in humans and for use in clinical practice for counseling the client who requires a choline-controlled diet.\",\n \"title\": \"Choline- and betaine-defined diets for use in clinical research and for the management of trimethylaminuria.\"\n },\n {\n \"docid\": \"MED-5184\",\n \"text\": \"We examined the association of dietary lignan intake with estrogen receptor negative (ER-) and ER positive (ER+) breast cancer risk in a breast cancer case-control study. Among premenopausal women only, there was a reduced risk of ER- breast cancer for those in the highest compared to the lowest quartile of lignan intake suggesting that the observed negative association of lignans with breast cancer may be limited to ER- tumors.\",\n \"title\": \"Dietary lignan intakes and risk of breast cancer by tumor estrogen receptor status.\"\n },\n {\n \"docid\": \"MED-3198\",\n \"text\": \"BACKGROUND: Despite its high content of saturated fatty acids, cheese does not seem to increase plasma total and LDL-cholesterol concentrations when compared with an equivalent intake of fat from butter. This effect may be due to the high calcium content of cheese, which results in a higher excretion of fecal fat. OBJECTIVES: The objective was to compare the effects of diets of equal fat content rich in either hard cheese or butter or a habitual diet on blood pressure and fasting serum blood lipids, C-reactive protein, glucose, and insulin. We also examined whether fecal fat excretion differs with the consumption of cheese or butter. DESIGN: The study was a randomized dietary intervention consisting of two 6-wk crossover periods and a 14-d run-in period during which the subjects consumed their habitual diet. The study included 49 men and women who replaced part of their habitual dietary fat intake with 13% of energy from cheese or butter. RESULTS: After 6 wk, the cheese intervention resulted in lower serum total, LDL-, and HDL-cholesterol concentrations and higher glucose concentrations than did the butter intervention. Cheese intake did not increase serum total or LDL-cholesterol concentrations compared with the run-in period, during which total fat and saturated fat intakes were lower. Fecal fat excretion did not differ between the cheese and butter periods. CONCLUSION: Cheese lowers LDL cholesterol when compared with butter intake of equal fat content and does not increase LDL cholesterol compared with a habitual diet. This trial is registered at clinicaltrials.gov as NCT01140165.\",\n \"title\": \"Cheese intake in large amounts lowers LDL-cholesterol concentrations compared with butter intake of equal fat content.\"\n },\n {\n \"docid\": \"MED-3369\",\n \"text\": \"Background: Strategies are needed to increase children's intake of a variety of vegetables, including vegetables that are not well liked. Objective: We investigated whether incorporating puréed vegetables into entrées to reduce the energy density (ED; in kcal/g) affected vegetable and energy intake over 1 d in preschool children. Design: In this crossover study, 3- to 5-y-old children (n = 40) were served all meals and snacks 1 d/wk for 3 wk. Across conditions, entrées at breakfast, lunch, dinner, and evening snack were reduced in ED by increasing the proportion of puréed vegetables. The conditions were 100% ED (standard), 85% ED (tripled vegetable content), and 75% ED (quadrupled vegetable content). Entrées were served with unmanipulated side dishes and snacks, and children were instructed to eat as much as they liked. Results: The daily vegetable intake increased significantly by 52 g (50%) in the 85% ED condition and by 73 g (73%) in the 75% ED condition compared with that in the standard condition (both P < 0.0001). The consumption of more vegetables in entrées did not affect the consumption of the vegetable side dishes. Children ate similar weights of food across conditions; thus, the daily energy intake decreased by 142 kcal (12%) from the 100% to 75% ED conditions (P < 0.05). Children rated their liking of manipulated foods similarly across ED amounts. Conclusion: The incorporation of substantial amounts of puréed vegetables to reduce the ED of foods is an effective strategy to increase the daily vegetable intake and decrease the energy intake in young children. This trial was registered at clinicaltrials.gov as NCT01252433.\",\n \"title\": \"Hiding vegetables to reduce energy density: an effective strategy to increase children's vegetable intake and reduce energy intake\"\n },\n {\n \"docid\": \"MED-4919\",\n \"text\": \"OBJECTIVE: Mass screening for celiac disease is controversial. The objective of this study was to determine whether detection of childhood celiac disease by mass screening improves long-term health status and health-related quality of life. METHODS: We conducted a prospective 10-year follow-up study of 32 children who were aged 2 to 4 years, had celiac disease identified by mass screening, and had a gluten-free diet (19) or a normal gluten-containing diet (13). The follow-up included assessments of general health status, celiac disease-associated symptoms, celiac disease-associated serum antibodies, and health-related quality of life. RESULTS: Ten years after mass screening, 81% of the children were adhering to a gluten-free diet. The health status improved in 66% of the treated children: in 41% by early treatment and in 25% by prevention of the gluten-dependent symptoms that they developed after diagnosis. For 19% of the children, treatment after screening would not have improved their health status, because they had no symptoms at screening and have remained symptom-free while consuming gluten. The health-related quality of life of the children with symptoms improved significantly after 1 year of gluten-free diet. Ten years after screening, the health-related quality of life of the children with celiac disease was similar to that of the reference population. CONCLUSION: Identification by mass screening led 10 years later to health improvement in 66% of children without deterioration of generic health-related quality of life. There is a good compliance after mass screening. In a research setting, delaying treatment for children without symptoms seems to be an option after a positive screening test. Long-term follow-up studies are needed to assess possible long-term complications in untreated, nonsymptomatic celiac disease.\",\n \"title\": \"Long-term health and quality-of-life consequences of mass screening for childhood celiac disease: a 10-year follow-up study.\"\n },\n {\n \"docid\": \"MED-2588\",\n \"text\": \"Objective Low-carbohydrate diets and their combination with high-protein diets have been gaining widespread popularity to control weight. In addition to weight loss, they may have favorable short-term effects on the risk factors of cardiovascular disease (CVD). Our objective was to elucidate their long-term effects on mortality and CVD incidence. Data sources MEDLINE, EMBASE, ISI Web of Science, Cochrane Library, and ClinicalTrials.gov for relevant articles published as of September 2012. Cohort studies of at least one year’s follow-up period were included. Review methods Identified articles were systematically reviewed and those with pertinent data were selected for meta-analysis. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) for all-cause mortality, CVD mortality and CVD incidence were calculated using the random-effects model with inverse-variance weighting. Results We included 17 studies for a systematic review, followed by a meta-analysis using pertinent data. Of the 272,216 people in 4 cohort studies using the low-carbohydrate score, 15,981 (5.9%) cases of death from all-cause were reported. The risk of all-cause mortality among those with high low-carbohydrate score was significantly elevated: the pooled RR (95% CI) was 1.31 (1.07–1.59). A total of 3,214 (1.3%) cases of CVD death among 249,272 subjects in 3 cohort studies and 5,081 (2.3%) incident CVD cases among 220,691 people in different 4 cohort studies were reported. The risks of CVD mortality and incidence were not statistically increased: the pooled RRs (95% CIs) were 1.10 (0.98–1.24) and 0.98 (0.78–1.24), respectively. Analyses using low-carbohydrate/high-protein score yielded similar results. Conclusion Low-carbohydrate diets were associated with a significantly higher risk of all-cause mortality and they were not significantly associated with a risk of CVD mortality and incidence. However, this analysis is based on limited observational studies and large-scale trials on the complex interactions between low-carbohydrate diets and long-term outcomes are needed.\",\n \"title\": \"Low-Carbohydrate Diets and All-Cause Mortality: A Systematic Review and Meta-Analysis of Observational Studies\"\n },\n {\n \"docid\": \"MED-4205\",\n \"text\": \"Since the Second World War the consumer behaviour in developed countries changed drastically. Primarily there existed the demand for sufficient food after a period of starvation, afterwards the desire for higher quality was arising, whereas today most people ask for safe and healthy food with high quality. Therefore a united approach comprising consistent standards, sound science and robust controls is required to ensure consumers' health and to maintain consumers' confidence and satisfaction. Chemical analysis along the whole food chain downstream (tracking) from primary production to the consumer and upstream (tracing) from the consumer to primary production is an important prerequisite to ensure food safety and quality. In this frame the focus of the following paper is the \\\"chemical safety of meat and meat products\\\" taking into account inorganic as well as organic residues and contaminants, the use of nitrite in meat products, the incidence of veterinary drugs, as well as a Failure Mode and Effect Analysis (FMEA) system assessing (prioritizing) vulnerable food chain steps to decrease or eliminate vulnerability.\",\n \"title\": \"Chemical safety of meat and meat products.\"\n },\n {\n \"docid\": \"MED-2353\",\n \"text\": \"Summary Anti-Gal is the most abundant natural antibody in humans, constituting ∼ 1% of immunoglobulins. Anti-Gal is naturally produced also in apes and Old World monkeys. The ligand of anti-Gal is a carbohydrate antigen called the ‘α-gal epitope’ with the structure Galα1-3Galβ1-4GlcNAc-R. The α-gal epitope is present as a major carbohydrate antigen in non-primate mammals, prosimians and New World monkeys. Anti-Gal can contributes to several immunological pathogeneses. Anti-Gal IgE produced in some individuals causes allergies to meat and to the therapeutic monoclonal antibody cetuximab, all presenting α-gal epitopes. Aberrant expression of the α-gal epitope or of antigens mimicking it in humans may result in autoimmune processes, as in Graves' disease. α-Gal epitopes produced by Trypanosoma cruzi interact with anti-Gal and induce ‘autoimmune like’ inflammatory reactions in Chagas' disease. Anti-Gal IgM and IgG further mediate rejection of xenografts expressing α-gal epitopes. Because of its abundance, anti-Gal may be exploited for various clinical uses. It increases immunogenicity of microbial vaccines (e.g. influenza vaccine) presenting α-gal epitopes by targeting them for effective uptake by antigen-presenting cells. Tumour lesions are converted into vaccines against autologous tumour-associated antigens by intra-tumoral injection of α-gal glycolipids, which insert into tumour cell membranes. Anti-Gal binding to α-gal epitopes on tumour cells targets them for uptake by antigen-presenting cells. Accelerated wound healing is achieved by application of α-gal nanoparticles, which bind anti-Gal, activate complement, and recruit and activate macrophages that induce tissue regeneration. This therapy may be of further significance in regeneration of internally injured tissues such as ischaemic myocardium and injured nerves.\",\n \"title\": \"Anti-Gal: an abundant human natural antibody of multiple pathogeneses and clinical benefits\"\n },\n {\n \"docid\": \"MED-1801\",\n \"text\": \"OBJECTIVE: In 1976, the Royal College of Physicians and the British Cardiac Society recommended eating less fatty red meat and more poultry instead because it was lean. However, the situation has changed since that time, with a striking increase in fat content of the standard broiler chicken. The aim of the present study was to report a snapshot of data on fat in chickens now sold to the public. DESIGN: Samples were obtained randomly between 2004 and 2008 from UK supermarkets, farm shops and a football club. The amount of chicken fat was estimated by emulsification and chloroform/methanol extraction. SETTING: Food sold in supermarkets and farms in England. SUBJECTS: Chicken samples. RESULTS: The fat energy exceeded that of protein. There has been a loss of n-3 fatty acids. The n-6:n-3 ratio was found to be as high as 9:1, as opposed to the recommendation of about 2:1. Moreover, the TAG level in the meat and whole bird mostly exceeded the proportion of phospholipids, which should be the higher for muscle function. The n-3 fatty acid docosapentaenoic acid (DPA, 22 : 5n-3) was in excess of DHA (22 : 6n-3). Previous analyses had, as usual for birds, more DHA than DPA. CONCLUSIONS: Traditional poultry and eggs were one of the few land-based sources of long-chain n-3 fatty acids, especially DHA, which is synthesized from its parent precursor in the green food chain. In view of the obesity epidemic, chickens that provide several times the fat energy compared with protein seem illogical. This type of chicken husbandry needs to be reviewed with regard to its implications for animal welfare and human nutrition.\",\n \"title\": \"Modern organic and broiler chickens sold for human consumption provide more energy from fat than protein.\"\n },\n {\n \"docid\": \"MED-3928\",\n \"text\": \"Seven patients with Parkinson's disease who experienced severe motor fluctuations in response to levodopa were studied in detail with relation to the effect of dietary protein on their motor function. The levodopa dose for each patient was not changed during the period of study, and no other antiparkinsonian drugs were used. Regular and high-protein diets resulted in a marked elevation in the plasma concentrations of large neutral amino acids (LNAAs) that are known to compete with levodopa for transport across the blood-brain barrier. Despite elevated plasma levodopa levels, all patients with elevated LNAA levels experienced parkinsonian symptoms. When the amino acid level dropped while plasma levodopa levels were elevated, patients experienced relief of these symptoms. On a low-protein diet, LNAA levels remained low and all patients were consistently dyskinetic throughout the day, even though the mean plasma levodopa levels were somewhat lower than when the patients consumed a high-protein diet. A redistribution diet that is virtually protein free until supper and then unrestricted until bedtime is tolerated by patients because this simple manipulation permits near-normal daytime motor function.\",\n \"title\": \"Plasma levels of amino acids correlate with motor fluctuations in parkinsonism.\"\n },\n {\n \"docid\": \"MED-1715\",\n \"text\": \"Summary Reduced function mutations in the insulin/IGF-I signaling pathway increase maximal lifespan and health span in many species. Calorie restriction (CR) decreases serum IGF-1 concentration by ~40%, protects against cancer and slows aging in rodents. However, the long-term effects of CR with adequate nutrition on circulating IGF-1 levels in humans are unknown. Here we report data from two long-term CR studies (1 and 6 years) showing that severe CR without malnutrition did not change IGF-1 and IGF-1 : IGFBP-3 ratio levels in humans. In contrast, total and free IGF-1 concentrations were significantly lower in moderately protein-restricted individuals. Reducing protein intake from an average of 1.67 g kg −1 of body weight per day to 0.95 g kg −1 of body weight per day for 3 weeks in six volunteers practicing CR resulted in a reduction in serum IGF-1 from 194 ng mL −1 to 152 ng mL −1 . These findings demonstrate that, unlike in rodents, long-term severe CR does not reduce serum IGF-1 concentration and IGF-1 : IGFBP-3 ratio in humans. In addition, our data provide evidence that protein intake is a key determinant of circulating IGF-1 levels in humans, and suggest that reduced protein intake may become an important component of anticancer and anti-aging dietary interventions.\",\n \"title\": \"Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans\"\n },\n {\n \"docid\": \"MED-1619\",\n \"text\": \"BACKGROUND: Diets rich in carbohydrates with a low glycemic index and with high fiber content are associated with flat post-prandial rises of blood glucose, minimal post-prandial insulin secretion and maintenance of insulin sensitivity. Protective food commodities in the prevention of cardiovascular disease, insulin resistance syndrome or diabetes are crucial components of the vegetarian diet. AIM OF THE STUDY: Insulin resistance values were assessed in relation to different nutrition. Metabolic abnormality is a predictor of age-related diseases and can be more pronounced in obese subjects. Insulin resistance values in normal weight subjects of two different nutritional habits were correlated with age. METHODS: Fasting concentrations of glucose and insulin as well as calculated values of insulin resistance IR (HOMA) were assessed in two nutritional groups of apparently healthy adult subjects (age range 19 - 64 years) with normal weight (body mass index 18.6 - 25.0 kg/m(2)): a vegetarian group (95 long-term lacto-ovo-vegetarians; duration of vegetarianism 10.2 +/- 0.5 years) and a non-vegetarian control group (107 subjects of general population on traditional western diet). Intake of energy and main nutrients (fats, saccharides, proteins) was similar in both groups. RESULTS: Glucose and insulin concentrations and IR (HOMA) values were significantly lower in vegetarians (glucose 4.47 +/- 0.05 vs. 4.71 +/- 0.07 mmol/l; insulin 4.96 +/- 0.23 vs. 7.32 +/- 0.41 mU/l; IR (HOMA) 0.99 +/- 0.05 vs. 1.59 +/- 0.10). IR (HOMA) dependence on age was only significant in subjects on a western diet. A significant increase of IR was found already in the age range 31-40 years, compared to vegetarians and it continued in later age decades. Age independent and low insulin resistance values in vegetarians are a consequence of an effective diet prevention by long-term frequent consumption of protective food. Vegetarians had a significantly higher consumption of whole grain products, pulses, products from oat and barley. CONCLUSION: The results of age independent and low values of insulin resistance document a beneficial effect of long-term vegetarian nutrition in prevention of metabolic syndrome, diabetes and cardiovascular disease.\",\n \"title\": \"No evidence of insulin resistance in normal weight vegetarians. A case control study.\"\n },\n {\n \"docid\": \"MED-2360\",\n \"text\": \"Lyme-like illness (also known as southern tick-associated rash illness [STARI] or Masters disease) is vectored by the Lone Star tick (Amblyomma americanum). Lyme-like illness lesions, which are similar to the erythema migrans rash of Lyme disease, tend to have lymphocytic dermal infiltrates. With the exception of Borrelia lonestari, the possible causative agent or agents of Lyme-like illness have not been cultured. More research is needed to fully understand this newly recognized zoonosis. Clinicians are encouraged to increase their knowledge and awareness of this Lyme disease mimic.\",\n \"title\": \"STARI, or Masters disease: Lone Star tick-vectored Lyme-like illness.\"\n },\n {\n \"docid\": \"MED-4051\",\n \"text\": \"The food mutagens IQ (2-amino-3-methylimidazo[4,5-f]quinoline) and PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) are heterocyclic amines (HCA), generated when heating proteinaceous food. This study investigates the protective potential of the flavonoids quercetin (Q) and rutin (R) against oxidative stress induced in vitro by IQ and PhIP in lymphocytes from healthy individuals and untreated, newly diagnosed colon cancer patients using the Comet assay. In the presence of up to 500μM Q and R, the DNA damage resulting from a high dose of PhIP (75μM) or IQ (150μM) was significantly reduced (P<0.001) to levels comparable to six times lower IQ or 7.5 times lower PhIP doses. Lymphocytes from colon cancer patients had greater baseline DNA damage than those from healthy individuals (P<0.01) and this higher level of damage was also observed throughout in vitro treatment. Except for the >50years of age group and male gender, confounding factors such as smoking, drinking and/or dietary habits were not found to be significant. In conclusion, flavonoids reduced oxidative stress caused by food mutagens in vitro in lymphocytes of healthy individuals and colon cancer patients. Thus, dietary supplementation with flavonoid-rich vegetables and fruits may prove very effective in protecting against oxidative stress. Copyright © 2011 Elsevier Ltd. All rights reserved.\",\n \"title\": \"The protective effect of the flavonoids on food-mutagen-induced DNA damage in peripheral blood lymphocytes from colon cancer patients.\"\n },\n {\n \"docid\": \"MED-2643\",\n \"text\": \"The incidence and/or prevalence of health problems associated with endocrine-disruption have increased. Many chemicals have endocrine-disrupting properties, including bisphenol A, some organochlorines, polybrominated flame retardants, perfluorinated substances, alkylphenols, phthalates, pesticides, polycyclic aromatic hydrocarbons, alkylphenols, solvents, and some household products including some cleaning products, air fresheners, hair dyes, cosmetics, and sunscreens. Even some metals were shown to have endocrine-disrupting properties. Many observations suggesting that endocrine disruptors do contribute to cancer, diabetes, obesity, the metabolic syndrome, and infertility are listed in this paper. An overview is presented of mechanisms contributing to endocrine disruption. Endocrine disruptors can act through classical nuclear receptors, but also through estrogen-related receptors, membrane-bound estrogen-receptors, and interaction with targets in the cytosol resulting in activation of the Src/Ras/Erk pathway or modulation of nitric oxide. In addition, changes in metabolism of endogenous hormones, cross-talk between genomic and nongenomic pathways, cross talk with estrogen receptors after binding on other receptors, interference with feedback regulation and neuroendocrine cells, changes in DNA methylation or histone modifications, and genomic instability by interference with the spindle figure can play a role. Also it was found that effects of receptor activation can differ in function of the ligand.\",\n \"title\": \"Endocrine-Disrupting Chemicals: Associated Disorders and Mechanisms of Action\"\n },\n {\n \"docid\": \"MED-1655\",\n \"text\": \"In 1940, a young German refugee physician scientist at Duke University in Durham, North Carolina began to treat patients with accelerated or \\\"malignant\\\" hypertension with a radical diet consisting of only white rice and fruit, with strikingly favorable results. He reported rapid reduction in blood pressure, rapid improvement in renal failure, papilledema, congestive heart failure and other manifestations of this previously fatal illness. This treatment was based on his theory that the kidney had both an excretory and a metabolic function, and that removing most of the sodium and protein burden from this organ enabled it to regain its normal ability to perform its more important metabolic functions. It was also effective in \\\"ordinary\\\" hypertension, in the absence of the dramatic vasculopathy of the accelerated form. The results were so dramatic that many experienced physicians suspected him of falsifying data. Among these results was the normalization of the ECG changes seen with hypertension. This paper reviews his published experience with this radical therapy, its controversial rise to fame, and its decline in popularity with the advent of effective antihypertensive drugs. It features the ECG changes seen in this then fatal disease, and the reversal of these changes by the rice diet. This treatment, though very difficult for the patient, produced effects which make it equal or superior to current multi-drug treatment of hypertension. A poorly known but important observation was that patients who were able to follow the regime, and who were slowly guided through a gradual modification of the diet over many months, were able to transition into a very tolerable low fat, largely vegetarian diet, while leading a normal, active life, without medications, indicating that the disease state had been permanently modified. Copyright © 2014 Elsevier Inc. All rights reserved.\",\n \"title\": \"An archaeologic dig: a rice-fruit diet reverses ECG changes in hypertension.\"\n },\n {\n \"docid\": \"MED-3275\",\n \"text\": \"In tissue cultures of normal adult and malignant mammalian cells, homocystine has been substituted for methionine in a medium rich in folic acid and cyanocobalamin. Normal adult cells thrive. Three highly malignant cell types from three different species, including man, die.\",\n \"title\": \"The Effect of Replacement of Methionine by Homocystine on Survival of Malignant and Normal Adult Mammalian Cells in Culture\"\n },\n {\n \"docid\": \"MED-2661\",\n \"text\": \"This paper presents the results of an investigation on the occurrence of alkylphenols (APs) and their ethoxylates (APEs) in 8 edible marine species from the Adriatic Sea and tries to estimate the corresponding intake for the Italian population. Two crustaceans, Nephrops norvegicus (Norway lobster) and Squilla mantis (spottail mantis shrimp), plus six fish species, Engraulis enchrascicolus (anchovy), Scomber scombrus (Atlantic mackerel), Merluccius merluccius (European hake), Mullus barbatus (red mullet), Solea vulgaris (common sole) and Lophius piscatorius (angler) were analyzed for their content of nonylphenol (NP), octylphenol (OP) and octylphenol polyethoxylates (OPEs). These compounds were found in all analysed samples. NP was detected at the highest concentrations: 118-399 and 9.5-1431 ng g(-1) fresh weight (fw) respectively in crustaceans and fish. OP was found at respective levels of 2.7-4.7 and 0.3-3.8 ng g(-1) fw in crustaceans and fish, whereas OPE was determined at respective concentrations of 1.2-16.8 and 0.2-21.1 ng g(-1) fw in the same species. These results, together with those from a previous study on 4 edible mollusc, allow to estimate respective daily intakes for NP, OP, and OPE of about 12, 0.1, and 0.1 microg day(-1) for an Italian adult living along the Adriatic Coast. In relation to NP and OP, these intakes are much lower than the doses associated with toxic effects in laboratory animals (9 mg kg(-1) bw for rats). Nevertheless, data of exposure from other sources to these chemicals and others with similar biological characteristics are needed.\",\n \"title\": \"Alkylphenols and alkylphenol ethoxylates contamination of crustaceans and fishes from the Adriatic Sea (Italy).\"\n },\n {\n \"docid\": \"MED-4313\",\n \"text\": \"BACKGROUND: Population-based studies have shown that vegetarians have lower body mass index than nonvegetarians, suggesting that vegetarian diet plans may be an approach for weight management. However, a perception exists that vegetarian diets are deficient in certain nutrients. OBJECTIVE: To compare dietary quality of vegetarians, nonvegetarians, and dieters, and to test the hypothesis that a vegetarian diet would not compromise nutrient intake when used to manage body weight. DESIGN: Cross-sectional analysis of National Health and Nutrition Examination Survey (1999-2004) dietary and anthropometric data. Diet quality was determined using United States Department of Agriculture's Healthy Eating Index 2005. Participants included adults aged 19 years and older, excluding pregnant and lactating women (N = 13,292). Lacto-ovo vegetarian diets were portrayed by intakes of participants who did not eat meat, poultry, or fish on the day of the survey (n = 851). Weight-loss diets were portrayed by intakes of participants who consumed 500 kcal less than their estimated energy requirements (n = 4,635). Mean nutrient intakes and body mass indexes were adjusted for energy, sex, and ethnicity. Using analysis of variance, all vegetarians were compared to all nonvegetarians, dieting vegetarians to dieting nonvegetarians, and nondieting vegetarians to nondieting nonvegetarians. RESULTS: Mean intakes of fiber, vitamins A, C, and E, thiamin, riboflavin, folate, calcium, magnesium, and iron were higher for all vegetarians than for all nonvegetarians. Although vegetarian intakes of vitamin E, vitamin A, and magnesium exceeded that of nonvegetarians (8.3 ± 0.3 vs 7.0 ± 0.1 mg; 718 ± 28 vs 603 ± 10 μg; 322 ± 5 vs 281 ± 2 mg), both groups had intakes that were less than desired. The Healthy Eating Index score did not differ for all vegetarians compared to all nonvegetarians (50.5 ± 0.88 vs 50.1 ± 0.33, P = 0.6). CONCLUSIONS: These findings suggest that vegetarian diets are nutrient dense, consistent with dietary guidelines, and could be recommended for weight management without compromising diet quality. Copyright © 2011 American Dietetic Association. Published by Elsevier Inc. All rights reserved.\",\n \"title\": \"A vegetarian dietary pattern as a nutrient-dense approach to weight management: an analysis of the national health and nutrition examination survey...\"\n },\n {\n \"docid\": \"MED-3136\",\n \"text\": \"The objective of this study was to determine the influence of frequent and long-term consumption of legume seeds on colonic function. Two groups of subjects were studied--one group habitually consumed legume seeds as part of their normal diet, a second group only infrequently consumed legumes. No differences between these groups could be detected for fecal output and frequency, intestinal transit time, VFA excretion or fecal pH during 23-day study periods in which subjects consumed either their usual diet or 100 g red kidney beans, daily. However, the addition of beans to the diets of both groups provided significantly more dietary fiber, and produced greater fecal output and a higher concentration of VFA in feces. Fecal output appeared to be determined by two independent parameters--dietary fiber intake and VFA excretion. Beans provided a physiologically useful source of dietary fiber and favorably influenced colonic function.\",\n \"title\": \"Influence of frequent and long-term bean consumption on colonic function and fermentation.\"\n },\n {\n \"docid\": \"MED-3217\",\n \"text\": \"To investigate whether systemic acid-base equilibrium changes with aging in normal adult humans, we reviewed published articles reporting the acid-base composition of arterial, arterialized venous, or capillary blood in age-identified healthy subjects. We extracted or calculated blood hydrogen ion concentration ([H+]), plasma bicarbonate concentration ([HCO3(-)]), blood PCO2, and age, and computed a total of 61 age-group means, distributed among eight 10-year intervals from age 20 to 100 years. Using linear regression analysis, we found that with increasing age, there is a significant increase in the steady-state blood [H+] (p < .001), and reduction in steady-state plasma [HCO3(-)] (p < .001), indicative of a progressively worsening low-level metabolic acidosis. Blood PCO2 decreased with age (p < .05), in keeping with the expected respiratory adaptation to metabolic acidosis. Such age-related increasing metabolic acidosis may reflect in part the normal decline of renal function with increasing age. The role of age-related metabolic acidosis in the pathogenesis of the degenerative diseases of aging warrants consideration.\",\n \"title\": \"Age and systemic acid-base equilibrium: analysis of published data.\"\n },\n {\n \"docid\": \"MED-4918\",\n \"text\": \"Background & Aims The historical prevalence and long-term outcome of undiagnosed celiac disease (CD) are unknown. We investigated the long-term outcome of undiagnosed CD and whether the prevalence of undiagnosed CD has changed during the past 50 years. Methods This study included 9,133 healthy young adults at Warren Air Force Base (sera were collected between 1948 and 1954) and 12,768 sex-matched subjects from 2 recent cohorts from Olmsted County, Minnesota, with either similar years of birth (n=5,558) or age at sampling (n=7,210) to that of the Air Force cohort. Sera were tested for tissue transglutaminase and, if abnormal, for endomysial antibodies. Survival was measured during a follow-up period of 45 years in the Air Force cohort. The prevalence of undiagnosed CD between the Air Force cohort and recent cohorts was compared. Results Of 9,133 persons from the Air Force cohort, 14 (0.2%) had undiagnosed CD. In this cohort, during 45 years of follow-up, all-cause mortality was greater in persons with undiagnosed CD than among those who were seronegative (hazard ratio=3.9; 95% CI, 2.0–7.5; P<.001). Undiagnosed CD was found in 68 (0.9%) persons with similar age at sampling and 46 (0.8%) persons with similar years of birth. The rate of undiagnosed CD was 4.5-fold and 4-fold greater in the recent cohorts (respectively) than in the Air Force cohort (both P ≤ .0001). Conclusions During 45 years of follow-up, undiagnosed CD was associated with a nearly 4-fold increased risk of death. The prevalence of undiagnosed CD appears to have increased dramatically in the United States during the past 50 years.\",\n \"title\": \"Increased Prevalence and Mortality in Undiagnosed Celiac Disease\"\n },\n {\n \"docid\": \"MED-3215\",\n \"text\": \"The average American diet, which is high in protein and low in fruits and vegetables, generates a large amount of acid, mainly as sulfates and phosphates. The kidneys respond to this dietary acid challenge with net acid excretion, as well as ammonium and titratable acid excretion. Concurrently, the skeleton supplies buffer by active resorption of bone. Indeed, calciuria is directly related to net acid excretion. Different food proteins differ greatly in their potential acid load, and therefore in their acidogenic effect. A diet high in acid-ash proteins causes excessive calcium loss because of its acidogenic content. The addition of exogenous buffers, as chemical salts or as fruits and vegetables, to a high protein diet results in a less acid urine, a reduction in net acid excretion, reduced ammonium and titratable acid excretion, and decreased calciuria. Bone resorption may be halted, and bone accretion may actually occur. Alkali buffers, whether chemical salts or dietary fruits and vegetables high in potassium, reverse acid-induced obligatory urinary calcium loss. We conclude that excessive dietary protein from foods with high potential renal acid load adversely affects bone, unless buffered by the consumption of alkali-rich foods or supplements.\",\n \"title\": \"Excess dietary protein can adversely affect bone.\"\n },\n {\n \"docid\": \"MED-3229\",\n \"text\": \"High-protein (HP) diets exert a hypercalciuric effect at constant levels of calcium intake, even though the effect may depend on the nature of the dietary protein. Lower urinary pH is also consistently observed for subjects consuming HP diets. The combination of these two effects was suspected to be associated with a dietary environment favorable for demineralization of the skeleton. However, increased calcium excretion due to HP diet does not seem to be linked to impaired calcium balance. In contrast, some data indicate that HP intakes induce an increase of intestinal calcium absorption. Moreover, no clinical data support the hypothesis of a detrimental effect of HP diet on bone health, except in a context of inadequate calcium supply. In addition, HP intake promotes bone growth and retards bone loss and low-protein diet is associated with higher risk of hip fractures. The increase of acid and calcium excretion due to HP diet is also accused of constituting a favorable environment for kidney stones and renal diseases. However, in healthy subjects, no damaging effect of HP diets on kidney has been found in either observational or interventional studies and it seems that HP diets might be deleterious only in patients with preexisting metabolic renal dysfunction. Thus, HP diet does not seem to lead to calcium bone loss, and the role of protein seems to be complex and probably dependent on other dietary factors and the presence of other nutrients in the diet.\",\n \"title\": \"Protein intake, calcium balance and health consequences.\"\n },\n {\n \"docid\": \"MED-3313\",\n \"text\": \"INTRODUCTION: Asbestos is banned in most Western countries but related malignancies are still of clinical concern because of their long latencies. This review identifies and addresses some controversial occupational and clinical aspects of asbestos-related malignancies. METHODS: Papers published in English from 1980 to 2009 were retrieved from PubMed. A total of 307 original articles were identified and 159 were included. ASSESSMENT OF EXPOSURE: The retrospective assessment of exposure is usually performed by using questionnaires and job exposure matrices and by careful collection of medical history. In this way crucial information about manufacturing processes and specific jobs can be obtained. In addition, fibers and asbestos bodies are counted in lung tissue, broncho-alveolar lavage, and sputum, but different techniques and interlaboratory variability hamper the interpretation of reported measurements. SCREENING FOR MALIGNANCIES: The effectiveness of low-dose chest CT screening in exposed workers is debatable. Several biomarkers have also been considered to screen individuals at risk for lung cancer and mesothelioma but reliable signatures are still missing. ATTRIBUTION OF LUNG CANCER: Exposures correlating with lung cancer are high and in the same range where asbestosis occurs. However, the unresolved question is whether the presence of fibrosis is a requirement for the attribution of lung cancer to asbestos. The etiology of lung cancer is difficult to define in cases of low-level asbestos exposure and concurrent smoking habits. MESOTHELIOMA: The diagnosis of malignant mesothelioma may also be difficult, because of procedures in sampling, fixation, and processing, and uses of immunohistochemical probes. CONCLUSIONS: Assessment of exposure is crucial and requires accurate medical and occupational histories. Quantitative analysis of asbestos body burden is better performed in digested lung tissues by counting asbestos bodies by light microscopy and/or uncoated fibers by transmission electron microscopy. The benefits of screenings for asbestos-related malignancies are equivocal. The attribution of lung cancer to asbestos exposure is difficult in a clinical setting because of the need to assess asbestos body burden and the fact that virtually all these patients are also tobacco smokers or former smokers. Given the premise that asbestosis is necessary to causally link lung cancer to asbestos, it follows that the assessment of both lung fibrosis and asbestos body burden is necessary.\",\n \"title\": \"Occupational toxicology of asbestos-related malignancies.\"\n },\n {\n \"docid\": \"MED-2366\",\n \"text\": \"Glycoconjugates and their antibodies are vital components of host-tumor interaction. This review concentrates on the oncological implications of research concerning the alpha gal triad; the alpha 1-->3 galactosyl epitope (alpha Gal), the enzyme responsible for its construction, alpha 1,3 galactosyl transferase (alpha 1-3GT), and its associated antibody: anti-gal. Alpha gal epitopes, previously assumed to be absent from human tissue, have been demonstrated on several human cancer cell lines, senescent red blood cells, and Graves' disease thyrocytes. Alpha-gal presence on neoplastic lines is correlated with increased metastatic formation in animal models. The mechanisms of human response to these neoantigens are complex, as natural anti-gal antibodies exist in high titers in normal sera, thus predicting immunological recognition of cells expressing alpha gal epitopes. Hypotheses vary regarding the pathogenic contributions of metastasis-associated phenomena such as de novo expression of alpha gal and its unmasking by desialylation. The means by which alpha gal is sporadically expressed in human tissue remain unknown, as the galactosyl transferase which produces this epitope in constitutively expressive animals has undergone significant mutation at the genomic level in humans. Pathological re-expression is presumed to require permissive changes at a cellular level. Detailing these alterations is a prerequisite to the comprehension of the metastatic phenotype. In this context, the possibility of therapeutic strategies affecting alpha gal expression are also discussed.\",\n \"title\": \"A possible role for the alpha 1-->3 galactosyl epitope and the natural anti-gal antibody in oncogenesis.\"\n },\n {\n \"docid\": \"MED-3276\",\n \"text\": \"Methionine is an essential amino acid with many key roles in mammalian metabolism such as protein synthesis, methylation of DNA and polyamine synthesis. Restriction of methionine may be an important strategy in cancer growth control particularly in cancers that exhibit dependence on methionine for survival and proliferation. Methionine dependence in cancer may be due to one or a combination of deletions, polymorphisms or alterations in expression of genes in the methionine de novo and salvage pathways. Cancer cells with these defects are unable to regenerate methionine via these pathways. Defects in the metabolism of folate may also contribute to the methionine dependence phenotype in cancer. Selective killing of methionine dependent cancer cells in co-culture with normal cells has been demonstrated using culture media deficient in methionine. Several animal studies utilizing a methionine restricted diet have reported inhibition of cancer growth and extension of a healthy life-span. In humans, vegan diets, which can be low in methionine, may prove to be a useful nutritional strategy in cancer growth control. The development of methioninase which depletes circulating levels of methionine may be another useful strategy in limiting cancer growth. The application of nutritional methionine restriction and methioninase in combination with chemotherapeutic regimens is the current focus of clinical studies. Copyright © 2012 Elsevier Ltd. All rights reserved.\",\n \"title\": \"A review of methionine dependency and the role of methionine restriction in cancer growth control and life-span extension.\"\n },\n {\n \"docid\": \"MED-3292\",\n \"text\": \"The human APOBEC3G protein is an innate anti-viral factor that can dominantly inhibit the replication of some endogenous and exogenous retroviruses. The prospects of purposefully harnessing such an anti-viral defense are under investigation. Here, long-term co-culture experiments were used to show that porcine endogenous retrovirus (PERV) transmission from pig to human cells is reduced to nearly undetectable levels by expressing human APOBEC3G in virus-producing pig kidney cells. Inhibition occurred by a deamination-independent mechanism, likely after particle production but before the virus could immortalize by integration into human genomic DNA. PERV inhibition did not require the DNA cytosine deaminase activity of APOBEC3G and, correspondingly, APOBEC3G-attributable hypermutations were not detected. In contrast, over-expression of the sole endogenous APOBEC3 protein of pigs failed to interfere significantly with PERV transmission. Together, these data constitute the first proof-of-principle demonstration that APOBEC3 proteins can be used to fortify the innate anti-viral defenses of cells to prevent the zoonotic transmission of an endogenous retrovirus. These studies suggest that human APOBEC3G-transgenic pigs will provide safer, PERV-less xenotransplantation resources and that analogous cross-species APOBEC3-dependent restriction strategies may be useful for thwarting other endogenous as well as exogenous retrovirus infections.\",\n \"title\": \"The Restriction of Zoonotic PERV Transmission by Human APOBEC3G\"\n },\n {\n \"docid\": \"MED-3310\",\n \"text\": \"We observed five consecutive cases of Hypersensitivity Pneumonitis in subjects working in a salami factory. The workers had to clean the white mould growing on salami surface using a manual wire brush. The five patients (four female) had a mean age of 39 +/- 15 years; two were smokers. Three patients had an acute clinical presentation with fever, dyspnoea, dry cough, oxygen desaturation, and presented at the emergency department with suspected diagnosis of community acquired pneumonia. The mean latency for developing respiratory symptoms was 11.6 days. Pulmonary function test demonstrated a reduction in diffusing capacity (DLCO) in all 5 patients (60 +/- 15% of predicted value). Skin prick test was positive for Penicillium spp in 3 cases and for Cladosporium and Aspergillus spp in 2 others. Specific IgG antibodies against Penicillium spp were positive in 3 subjects; 2 were positive for Aspergillus Fumigatus. The prevailing radiological pattern was a ground glass appearance in the three patients with acute clinical onset and a centrilobular one in patients with subacute onset. All patients were advised to avoid exposure to the antigens. Follow-up visits including pulmonary function testing, and DLCO measurement were conducted at one, three and six months. HRCT was performed at six month. Four subjects had a complete radiological and clinical resolution after changing work. Only one patient was treated with oral steroids for severe dyspnoea and progressive reduction of DLCO, gaining a complete radiological and clinical stability at six months.\",\n \"title\": \"A new type of Hypersensitivity Pneumonitis: salami brusher's disease.\"\n },\n {\n \"docid\": \"MED-1617\",\n \"text\": \"Background Dietary modification via caloric restriction is associated with multiple effects related to improved metabolic and cardiovascular health. However, a mandated reduction in kilocalories is not well-tolerated by many individuals, limiting the long-term application of such a plan. The Daniel Fast is a widely utilized fast based on the Biblical book of Daniel. It involves a 21 day ad libitum food intake period, devoid of animal products and preservatives, and inclusive of fruits, vegetables, whole grains, legumes, nuts, and seeds. The purpose of the present study was to determine the efficacy of the Daniel Fast to improve markers of metabolic and cardiovascular disease risk. Methods 43 subjects (13 men; 30 women; 35 ± 1 yrs; range: 20-62 yrs) completed a 21 day period of modified food intake in accordance with detailed guidelines provided by investigators. All subjects purchased and prepared their own food. Following initial screening, subjects were given one week to prepare for the fast, after which time they reported to the lab for their pre-intervention assessment (day 1). After the 21 day fast, subjects reported to the lab for their post-intervention assessment (day 22). For both visits, subjects reported in a 12 hr fasted state, performing no strenuous physical activity during the preceding 24-48 hrs. At each visit, mental and physical health (SF-12 form), resting heart rate and blood pressure, and anthropometric variables were measured. Blood was collected for determination of complete blood count, metabolic panel, lipid panel, insulin, HOMA-IR, and C-reactive protein (CRP). Subjects' self-reported compliance, mood, and satiety in relation to the fast were also recorded. Diet records were maintained by all subjects during the 7 day period immediately prior to the fast (usual intake) and during the final 7 days of the fast. Results Subjects' compliance to the fast was 98.7 ± 0.2% (mean ± SEM). Using a 10 point scale, subjects' mood and satiety were both 7.9 ± 0.2. The following variables were significantly (p < 0.05) lower following the fast as compared to before the fast: white blood cell count (5.68 ± 0.24 vs. 4.99 ± 0.19 103·μL-1), blood urea nitrogen (13.07 ± 0.58 vs. 10.14 ± 0.59 mg·dL-1), blood urea nitrogen/creatinine (14.74 ± 0.59 vs. 11.67 ± 0.68), protein (6.95 ± 0.07 vs. 6.77 ± 0.06 g·dL-1), total cholesterol (171.07 ± 4.57 vs. 138.69 ± 4.39 mg·dL-1), LDL-C (98.38 ± 3.89 vs. 76.07 ± 3.53 mg·dL-1), HDL-C (55.65 ± 2.50 vs. 47.58 ± 2.19 mg·dL-1), SBP (114.65 ± 2.34 vs. 105.93 ± 2.12 mmHg), and DBP (72.23 ± 1.59 vs. 67.00 ± 1.43 mmHg). Insulin (4.42 ± 0.52 vs. 3.37 ± 0.35 μU·mL-1; p = 0.10), HOMA-IR (0.97 ± 0.13 vs.0.72 ± 0.08; p = 0.10), and CRP (3.15 ± 0.91 vs. 1.60 ± 0.42 mg·L-1; p = 0.13), were lowered to a clinically meaningful, albeit statistically insignificant extent. No significant difference was noted for any anthropometric variable (p > 0.05). As expected, multiple differences in dietary intake were noted (p < 0.05), including a reduction in total kilocalorie intake (2185 ± 94 vs. 1722 ± 85). Conclusion A 21 day period of modified dietary intake in accordance with the Daniel Fast is 1) well-tolerated by men and women and 2) improves several risk factors for metabolic and cardiovascular disease. Larger scale, randomized studies, inclusive of a longer time period and possibly a slight modification in food choice in an attempt to maintain HDL cholesterol, are needed to extend these findings.\",\n \"title\": \"Effect of a 21 day Daniel Fast on metabolic and cardiovascular disease risk factors in men and women\"\n },\n {\n \"docid\": \"MED-3932\",\n \"text\": \"Background Caffeine consumption has been associated with a reduced risk of Parkinson disease. The association is strong and consistent in men, but uncertain in women, possibly because of an interaction with hormone replacement therapy. We sought to confirm these findings using data on Parkinson disease incidence in the CPS II Nutrition Cohort, a large prospective study of men and women. Methods We conducted a prospective study of caffeine intake and risk of PD within the Cancer Prevention Study II Nutrition Cohort. Intakes of coffee and other sources of caffeine were assessed at baseline. Incident cases of PD (n = 317; 197 men and 120 women) were confirmed by treating physicians and medical record review. Relative risks (RR) were estimated using proportional hazards models, adjusting for age, smoking and alcohol consumption. Results After adjustment for age, smoking and alcohol intake, high caffeine consumption was associated with a reduced risk of PD. The relative risk comparing the 5th to the 1st quintile of caffeine intake was 0.43 (CI: 0.26, 0.71, p-trend = <0.002) in men, and 0.61 (95% CI: 0.34, 1.09; p for trend =0.05) in women. Among women, this association was stronger among never users of hormone replacement therapy (RR=0.32) than among ever users (RR=0.81, p-interaction = 0.15). Consumption of decaffeinated coffee was not associated with PD risk. Conclusion Findings from this large prospective study of men and women are consistent with a protective effect of caffeine intake on PD incidence, with an attenuating influence of hormone replacement therapy in women.\",\n \"title\": \"Caffeine and risk of Parkinson disease in a large cohort of men and women\"\n },\n {\n \"docid\": \"MED-2359\",\n \"text\": \"INTRODUCTION: ALPHA-GAL is a glycoconjugate present on cell membranes of mammals and bacteria but not humans who display anti-Gal antibodies (AB) in high titers provoked by the commensal gut flora. In the present study, we sought to determine the longitudinal course of alpha-Gal specific AB titers of all isotypes over 8 weeks among healthy adult subjects. Furthermore, we hypothesized that inflammatory bowel disease (IBD) patients display increased anti-Gal titers. MATERIALS AND METHODS: We drew serum from healthy probands (n=20) weekly for 8 weeks and obtained plasma samples of from patients suffering from Crohn's disease (n=20) and ulcerative colitis (n=20). We measured anti-Gal ABs of all isotypes and total immunoglobulin (Ig) content using an enzyme-linked immunosorbent assay technique. For statistical evaluation of the longitudinal titers, we calculated confidence intervals for the slopes of a random intercept model, comparing variances between and within the probands. For group comparisons, we performed paired student t-tests and Pearson correlations. RESULTS: Alpha-Gal specific IgG, IgM, IgD, and IgA titers remained unvaried within a narrow range upon longitudinal observation. Most probands did not display alpha-Gal specific IgE ABs. Crohn's disease patients showed highly increased alpha-Gal-specific IgA titers compared with control subjects (P<.01). CONCLUSION: Apart from IgE, alpha-Gal-specific ABs of all isotypes remained constant over longer time periods in healthy subjects. Thus, significant titer changes actually represent increased antigen exposure and a specific anti-alpha-Gal response. Crohn's disease patients display increased anti-Gal IgA titers compared with healthy controls, which reflects a chronically impaired mucosal gut barrier in this patient cohort. Copyright © 2011 Elsevier Inc. All rights reserved.\",\n \"title\": \"Anti-Gal titers in healthy adults and inflammatory bowel disease patients.\"\n },\n {\n \"docid\": \"MED-2587\",\n \"text\": \"Recent research has demonstrated that successful simultaneous treatment of multiple risk factors including cholesterol, triglycerides, homocysteine, lipoprotein (a) [Lp(a)], fibrinogen, antioxidants, endothelial dysfunction, inflammation, infection, and dietary factors can lead to the regression of coronary artery disease and the recovery of viable myocardium. However, preliminary work revealed that a number of individuals enrolled in the original study went on popular high-protein diets in an effort to lose weight. Despite increasing numbers of individuals following high-protein diets, little or no information is currently available regarding the effect of these diets on coronary artery disease and coronary blood flow. Twenty-six people were studied for 1 year by using myocardial perfusion imaging (MPI), echocardiography (ECHO), and serial blood work to evaluate the extent of changes in regional coronary blood flow, regional wall motion abnormalities, and several independent variables known to be important in the development and progression of coronary artery disease. Treatment was based on homocysteine, Lp (a), C-reactive protein (C-RP), triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and fibrinogen levels. Each variable was independently treated as previously reported. MPI and ECHO were performed at the beginning and end of the study for each individual. The 16 people (treatment group/TG) studied modified their dietary intake as instructed. Ten additional individuals elected a different dietary regimen consisting of a \\\"high-protein\\\" (high protein group/HPG) diet, which they believed would \\\"improve\\\" their overall health. Patients in the TG demonstrated a reduction in each of the independent variables studied with regression in both the extent and severity of coronary artery disease (CAD) as quantitatively measured by MPI. Recovery of viable myocardium was seen in 43.75% of myocardial segments in these patients, documented with both MPI and ECHO evaluations. Individuals in the HPG showed worsening of their independent variables. Most notably, fibrinogen, Lp (a), and C-RP increased by an average of 14%, 106%, and 61% respectively. Progression of the extent and severity of CAD was documented in each of the vascular territories with an overall cumulative progression of 39.7%. The differences between progression and extension of disease in the HPG and the regression of disease in the TG were statistically (p<0.001) significant. Patients following recommended treatment for each of the independent variables were able to regress both the extent and severity of their coronary artery disease (CAD), as well as improve their myocardial wall motion (function) while following the prescribed medical and dietary guidelines. However, individuals receiving the same medical treatment but following a high-protein diet showed a worsening of independent risk factors, in addition to progression of CAD. These results would suggest that high-protein diets may precipitate progression of CAI) through increases in lipid deposition and inflammatory and coagulation pathways.\",\n \"title\": \"The effect of high-protein diets on coronary blood flow.\"\n },\n {\n \"docid\": \"MED-1249\",\n \"text\": \"The effect of dietary protein on the level of plasma cholesterol in young, healthy, normolipidemic women was investigated in two separate studies by feeding either a conventional diet containing mixed protein, or a plant protein diet in which the animal protein of the first diet was replaced by soy protein meat analogues and soy milk. The diets were similar with respect to carbohydrate, fat and sterol composition. The first study, lasting 73 days and involving six subjects, gave an indication that plasma cholesterol levels were lower on the plant protein diet. The second study, which incorporated a number of improvements based on experience, lasted 78 days and used a cross-over design involving two groups of five subjects each. In this study, the mean plasma cholesterol level was found to be significantly lower on the plant protein diet.\",\n \"title\": \"Hypocholesterolemic effect of substituting soybean protein for animal protein in the diet of healthy young women.\"\n },\n {\n \"docid\": \"MED-4164\",\n \"text\": \"PURPOSE OF REVIEW: This review discusses recent evidence that suggests a significant underestimation of protein requirements in adult humans. RECENT FINDINGS: Traditionally, total protein requirements for humans have been determined using nitrogen balance. The recent Dietary Reference Intake recommendations for mean and population-safe intakes of 0.66 and 0.8 g/kg/day, respectively, of high-quality protein in adult humans are based on a meta-analysis of nitrogen balance studies using single linear regression analysis. We reanalyzed existing nitrogen balance studies using two-phase linear regression analysis and obtained mean and safe protein requirements of 0.91 and 0.99 g/kg/day, respectively. The two-phase linear regression analysis is considered more appropriate for biological analysis of dose-response curves. Considering the inherent problems associated with the nitrogen balance method, we developed an alternative method, the indicator amino acid oxidation technique, to determine protein requirements The mean and population-safe requirements in adult men were determined to be 0.93 and 1.2 g/kg/day and are 41 and 50%, respectively, higher than the current Dietary Reference Intakes recommendations. SUMMARY: The indicator amino acid oxidation-based requirement values of 0.93 and 1.2 g protein/kg/day and the reanalysis of existing nitrogen balance studies are significantly higher than current recommendations. Therefore, there is an urgent need to reassess recommendations for protein intake in adult humans.\",\n \"title\": \"Evidence that protein requirements have been significantly underestimated.\"\n },\n {\n \"docid\": \"MED-2355\",\n \"text\": \"Anaphylaxis is a severe allergic reaction that can be rapidly progressing and fatal. In instances where the triggering allergen is not known, establishing the etiology of anaphylaxis is pivotal to long-term risk management. Our recent work has identified a novel IgE antibody (Ab) response to a mammalian oligosaccharide epitope, galactose-alpha-1,3-galactose (alpha-gal), that has been associated with two distinct forms of anaphylaxis: (1) immediate onset anaphylaxis during first exposure to intravenous cetuximab, and (2) delayed onset anaphylaxis 3–6 h after ingestion of mammalian food products (e.g., beef and pork). The results of our studies strongly suggest that tick bites are a cause, if not the only significant cause, of IgE Ab responses to alpha-gal in the southern, eastern and central United States. Patients with IgE Ab to alpha-gal continue to emerge and, increasingly, these cases involve children. This IgE Ab response cross-reacts with cat and dog but does not appear to pose a risk for asthma; however, it may impair diagnostic testing in some situations.\",\n \"title\": \"Delayed Anaphylaxis to Red Meat in Patients with IgE Specific for Galactose alpha-1,3-Galactose (alpha-gal)\"\n },\n {\n \"docid\": \"MED-3875\",\n \"text\": \"BACKGROUND: Mammalian lignans, enterolactone (EL) and enterodiol (ED), have been shown to inhibit breast and colon carcinoma. To date, there have been no reports of the effect of lignans on prostatic carcinoma. We investigated the effects of ED and EL on three human prostate cancer cell lines (PC-3, DU-145 and LNCaP). MATERIALS AND METHODS: Cells were treated with either 0.1% (v/v) DMSO (vehicle) or 10-100 microM of EL, ED or genistein (positive control) for 72 hours. Cell viability was measured by the propidium iodide nuclei staining fluorometric assay with each assay performed in triplicate. RESULTS: At 10-100 microM, EL significantly inhibited the growth of all cell lines, whereas ED only inhibited PC-3 and LNCaP cells. While EL was a more potent growth inhibitor than ED, both were less potent than genistein. The dose for 50% growth inhibition of LNCaP cells (IC50) by EL was 57 microM, whereas IC50 was 100 microM for ED, (the observed IC50 for genistein was 25 microM). CONCLUSION: ED and EL suppress the growth of prostate cancer cells, and may do so via hormonally-dependent and independent mechanisms.\",\n \"title\": \"Effect of mammalian lignans on the growth of prostate cancer cell lines.\"\n },\n {\n \"docid\": \"MED-3926\",\n \"text\": \"Sixteen parkinsonian patients with daily fluctuations in the clinical response to levodopa have been placed on a redistribution protein diet. The diet was virtually protein-free until the evening meal and then unrestricted until bedtime. While on the redistribution protein diet, a group of patients (5 out of 16) had a clear and significant benefit from dietary therapy showing a definite reduction of diurnal motor performance fluctuations. In addition, all patients tended to show an improvement and a more constant response to levodopa treatment. A trial of redistribution protein diet appears a simple, reasonable, worthwhile approach to PD patients who begin to experience oscillating clinical response to levodopa treatment.\",\n \"title\": \"Protein redistribution diet and antiparkinsonian response to levodopa.\"\n },\n {\n \"docid\": \"MED-2590\",\n \"text\": \"Nineteen people without prior history of documented heart disease were studied for 8 months to determine the effect of treatment based on an immunologic unified theory of vascular disease. Subjects underwent myocardial perfusion imaging to quantify the extent and severity of coronary artery disease, along with assessment of wall motion abnormalities and ejection fraction by both nuclear and echocardiographic methods. These tests were repeated at the end of the study. Treatment consisted of dietary changes, treatment of cholesterol, triglycerides, homocysteine, lipoprotein (a), fibrinogen, C-reactive protein, and infection. Patients who followed the dietary recommendations demonstrated statistically reduced disease in all three major coronary arteries, whereas those individuals who followed high-protein diets demonstrated statistically greater levels of disease.\",\n \"title\": \"Reversing heart disease in the new millennium--the Fleming unified theory.\"\n },\n {\n \"docid\": \"MED-3955\",\n \"text\": \"BACKGROUND Polybrominated Diphenyl Ethers (PBDEs), widely used as flame retardants since the 1970s, have exhibited endocrine disruption in experimental studies. Tetra- to hexa-BDE congeners are estrogenic, while hepta-BDE and 6-OH-BDE-47 are antiestrogenic. Most PBDEs also have antiandrogenic activity. It is not clear, however, whether PBDEs affect human reproduction. OBJECTIVES The analysis was designed to investigate the potential endocrine disruption of PBDEs on the age at menarche in adolescent girls. METHODS We analyzed the data from a sample of 271 adolescent girls (age 12–19 years) in the National Health and Nutrition Examination Survey (NHANES), 2003–2004. We estimated the associations between individual and total serum BDEs (BDE-28, -47, -99, -100, -153, and -154, lipid adjusted) and mean age at menarche. We also calculated the risk ratios (RRs) and 95% confidence intervals (CI) for menarche prior to age 12 years in relation to PBDE exposure. RESULTS The median total serum BDE concentration was 44.7 ng/g lipid. Higher serum PBDE concentrations were associated with slightly earlier ages at menarche. Each natural log unit of total BDEs was related to a change of −0.10 (95% CI: −0.33, 0.13) years of age at menarche and a RR of 1.60 (95% CI: 1.12, 2.28) for experiencing menarche before 12 years of age, after adjustment for potential confounders. CONCLUSION These data suggest high concentrations of serum PBDEs during adolescence are associated with a younger age of menarche.\",\n \"title\": \"Serum PBDEs and Age at Menarche in Adolescent Girls: Analysis of the National Health and Nutrition Examination Survey 2003–2004\"\n },\n {\n \"docid\": \"MED-3270\",\n \"text\": \"Aging affects all organisms and its basic mechanisms are expected to be conserved across species. Oxidation of proteins has been proposed to be one of the basic mechanisms linking oxygen radicals with the basic aging process. If oxidative damage to proteins is involved in aging, long-lived animals (which age slowly) should show lower levels of markers of this kind of damage than short-lived ones. However, this possibility has not been investigated yet. In this study, steady-state levels of markers of different kinds of protein damage--oxidation (glutamic and aminoadipic semialdehydes), mixed glyco- and lipoxidation (carboxymethyl- and carboxyethyllysine), lipoxidation (malondialdehydelysine) and amino acid composition--were measured in the heart of eight mammalian species ranging in maximum life span (MLSP) from 3.5 to 46 years. Oxidation markers were directly correlated with MLSP across species. Mixed glyco- and lipoxidation markers did not correlate with MLSP. However, the lipoxidation marker malondialdehydelysine was inversely correlated with MLSP (r2=0.85; P<0.001). The amino acid compositional analysis revealed that methionine is the only amino acid strongly correlated MLSP and that such correlation is negative (r2=0.93; P<0.001). This trait may contribute to lower steady-state levels of oxidized methionine residues in cellular proteins. These results reinforce the notion that high longevity in homeothermic vertebrates is achieved in part by constitutively decreasing the sensitivity of both tissue proteins and lipids to oxidative damage. This is obtained by modifying the constituent structural components of proteins and lipids, selecting those less sensitive to oxidative modifications.\",\n \"title\": \"Protein methionine content and MDA-lysine adducts are inversely related to maximum life span in the heart of mammals.\"\n },\n {\n \"docid\": \"MED-2999\",\n \"text\": \"Many of the commonest diseases in the economically more developed communities are characteristic of modern Western culture. Evidence is presented suggesting that they represent a failure of adaptation to the dramatic changes in diet that have been associated with the emergence of modern Western culture. Dietary changes aimed at the alleviation and prevention of these diseases are discussed and recommended.\",\n \"title\": \"Western diseases and their emergence related to diet.\"\n },\n {\n \"docid\": \"MED-4037\",\n \"text\": \"In the present study, 21 polycyclic aromatic hydrocarbon (PAH) congeners were measured in the exhaust stack of 3 types of restaurants: 9 Chinese, 7 Western, and 4 barbeque (BBQ). The total PAH concentration of BBQ restaurants (58.81 ± 23.89 μg m(-3)) was significantly higher than that of Chinese (20.99 ± 13.67 μg m(-3)) and Western (21.47 ± 11.44 μg m(-3)) restaurants. The total benzo[a]pyrene potency equivalent (B[a]P(eq)) concentrations, however, were highest in Chinese restaurants (1.82 ± 2.24 μg m(-3)), followed by Western (0.86 ± 1.43 μg m(-3), p<0.01) and BBQ-type restaurants (0.59 ± 0.55 μg m(-3), p<0.01). We further developed a probabilistic risk model to assess the incremental lifetime cancer risk (ILCR) for people exposed to carcinogenic PAHs. Because the exhaust stack directly affected the back-door neighbors of these restaurants, we were concerned with the real exposure of groups near the exhaust stack outlets of these restaurants. The ILCRs for total exposure of the neighbors (inhalation+dermal contact+ingestion) were 2.6-31.3, 1.5-14.8, and 1.3-12.2 × 10(-6) in Chinese, Western, and BBQ restaurants, respectively. We suggest that the maximum acceptable exposure time to the exhaust stack outlet area for Chinese, Western, and BBQ restaurants ranges between 5-19, 17-42, and 18-56 h month(-1), respectively, based on an ILCR of less than 10(-6). Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.\",\n \"title\": \"Carcinogenic potencies of polycyclic aromatic hydrocarbons for back-door neighbors of restaurants with cooking emissions.\"\n },\n {\n \"docid\": \"MED-2369\",\n \"text\": \"Background Carbohydrate moieties are frequently encountered in food and can elicit IgE responses, the clinical significance of which has been unclear. Recent work, however, has shown that IgE antibodies to galactose-α-1,3-galactose (α-gal), a carbohydrate commonly expressed on nonprimate mammalian proteins, are capable of eliciting serious, even fatal, reactions. Objective We sought to determine whether IgE antibodies to α-gal are present in sera from patients who report anaphylaxis or urticaria after eating beef, pork, or lamb. Methods Detailed histories were taken from patients presenting to the University of Virginia Allergy Clinic. Skin prick tests (SPTs), intradermal skin tests, and serum IgE antibody analysis were performed for common indoor, outdoor, and food allergens. Results Twenty-four patients with IgE antibodies to α-gal were identified. These patients described a similar history of anaphylaxis or urticaria 3 to 6 hours after the ingestion of meat and reported fewer or no episodes when following an avoidance diet. SPTs to mammalian meat produced wheals of usually less than 4 mm, whereas intradermal or fresh-food SPTs provided larger and more consistent wheal responses. CAP-RAST testing revealed specific IgE antibodies to beef, pork, lamb, cow’s milk, cat, and dog but not turkey, chicken, or fish. Absorption experiments indicated that this pattern of sensitivity was explained by an IgE antibody specific for α-gal. Conclusion We report a novel and severe food allergy related to IgE antibodies to the carbohydrate epitope α-gal. These patients experience delayed symptoms of anaphylaxis, angioedema, or urticaria associated with eating beef, pork, or lamb.\",\n \"title\": \"Delayed anaphylaxis, angioedema, or urticaria after consumption of red meat in patients with IgE antibodies specific for galactose-α-1,3-galactose\"\n },\n {\n \"docid\": \"MED-1620\",\n \"text\": \"Background The Daniel Fast is a vegan diet that prohibits the consumption of animal products, refined foods, white flour, preservatives, additives, sweeteners, flavorings, caffeine, and alcohol. Following this dietary plan for 21 days has been demonstrated to improve blood pressure, LDL-C, and certain markers of oxidative stress, but it has also been shown to lower HDL-C. Krill oil supplementation has been shown to increase HDL-C. Methods We investigated the effects of following a Daniel Fast dietary plan with either krill oil supplementation (2 g/day) or placebo supplementation (coconut oil; 2 g/day) for 21 days. The subjects in this study (12 men and 27 women) were heterogeneous with respect to body mass index (BMI) (normal weight, overweight, and obese), blood lipids (normolipidemic and hyperlipidemic), blood glucose (normal fasting glucose, impaired fasting glucose, and type 2 diabetic), and blood pressure (normotensive and hypertensive). Results Krill oil supplementation had no effect on any outcome measure (all p > 0.05), and so the data from the krill oil group and the placebo group were collapsed and analyzed to examine the effects of following a 21-day Daniel Fast. Significant reductions were observed in LDL-C (100.6 ± 4.3 mg/dL vs. 80.0 ± 3.7 mg/dL), the LDL:HDL ratio (2.0 ± 0.1 vs. 1.7 ± 0.1), fasting blood glucose (101.4 ± 7.5 mg/dL vs. 91.7 ± 3.4 mg/dL), fasting blood insulin (7.92 ± 0.80 μU/mL vs. 5.76 ± 0.59 μU/mL), homeostasis model assessment of insulin resistance (HOMA-IR) (2.06 ± 0.30 vs. 1.40 ± 0.21), systolic BP (110.7 ± 2.2 mm Hg vs. 105.5 ± 1.7 mm Hg), and body weight (74.1 ± 2.4 kg vs. 71.5 ± 2.3 kg) (all p < 0.05). Conclusion Following a Daniel Fast dietary plan improves a variety of cardiometabolic parameters in a wide range of individuals in as little as 21 days, and these improvements are unaffected by krill oil supplementation. Trial registration Clinicaltrial.govNCT01378767\",\n \"title\": \"A 21-day Daniel fast with or without krill oil supplementation improves anthropometric parameters and the cardiometabolic profile in men and women\"\n },\n {\n \"docid\": \"MED-3142\",\n \"text\": \"AIM: Soy foods are the major source of isoflavones, which are believed to play important roles in genesis of breast cancer and its progression. We here conducted a prospective study to evaluate the association of soy isoflavone food consumption with breast cancer prognosis. METHODS: A prospective study was performed from January 2004 and January 2006 in China. Trained interviewers conducted face-to-face interviews using a structured questionnaire to collect information on dietary habits and potential confounding factors. The relative risk [hazard ratio (HR)] and 95% CI were calculated from the Cox regression model for all significant predictors from cancer diagnosis to the endpoint of the study (event). RESULTS: After a median follow up of 52.1 months (range, 9-60 months), a total of 79 breast cancer related deaths were recorded in our study, risk being inversely associated with a high intake of soy isoflavone. With an average intake of soy isoflavone above 17.3 mg/day, the mortality of breast cancer can be reduced by about 38-36%. We also found the decreased breast cancer death with high soy protein intake, with a HR (95% CI) of 0.71 (0.52-0.98). Stratified analysis with reference to the ER status, further demonstrated a better prognosis of ER positive breast cancer with a high intake of soy isoflavone (HR 0.59, 0.40-0.93). CONCLUSION: Our study shows the soy food intake is associated with longer survival and low recurrence among breast cancer patients. A cohort study with a larger sample size and long term follow-up is now needed.\",\n \"title\": \"Positive effects of soy isoflavone food on survival of breast cancer patients in China.\"\n },\n {\n \"docid\": \"MED-1188\",\n \"text\": \"One hundred and eighteen missionaries working on 75 mission stations or hospitals in 24 sub-Saharan African countries provided information about their medical practice in the preceding year of 1981. Details were collected of the total number of patients seen and admitted during the year, and the number of cases of bloody diarrhoea, typhoid and inflammatory bowel disease. Over 1 million outpatients and about 190,000 inpatients were treated. These included 12,859 cases of bloody diarrhoea, of whom 1,914 had typhoid. Twenty-two cases of inflammatory bowel disease were also reported. Histological support was least available in West Africa and only 25% of hospitals had access to this facility. Nevertheless, the frequency with which inflammatory bowel disease in sub-Saharan Africa is difficult and limited by access to diagnostic facilities. It is likely to be some time before reliable estimates of the incidence and prevalence of Crohn's disease and ulcerative colitis in the rural African population can be made.\",\n \"title\": \"Inflammatory bowel disease in rural sub-Saharan Africa: rarity of diagnosis in patients attending mission hospitals.\"\n },\n {\n \"docid\": \"MED-1712\",\n \"text\": \"Diet contributes to over one-third of cancer deaths in the Western world, yet the factors in the diet that influence cancer are not elucidated. A reduction in caloric intake dramatically slows cancer progression in rodents, and this may be a major contribution to dietary effects on cancer. Insulin-like growth factor I (IGF-I) is lowered during dietary restriction (DR) in both humans and rats. Because IGF-I modulates cell proliferation, apoptosis, and tumorigenesis, the mechanisms behind the protective effects of DR may depend on the reduction of this multifaceted growth factor. To test this hypothesis, IGF-I was restored during DR to ascertain if lowering of IGF-I was central to slowing bladder cancer progression during DR. Heterozygous p53-deficient mice received a bladder carcinogen, p-cresidine, to induce preneoplasia. After confirmation of bladder urothelial preneoplasia, the mice were divided into three groups: (a) ad libitum; (b) 20% DR; and (c) 20% DR plus IGF-I (IGF-I/DR). Serum IGF-I was lowered 24% by DR but was completely restored in the IGF-I/DR-treated mice using recombinant IGF-I administered via osmotic minipumps. Although tumor progression was decreased by DR, restoration of IGF-I serum levels in DR-treated mice increased the stage of the cancers. Furthermore, IGF-I modulated tumor progression independent of changes in body weight. Rates of apoptosis in the preneoplastic lesions were 10 times higher in DR-treated mice compared to those in IGF/DR- and ad libitum-treated mice. Administration of IGF-I to DR-treated mice also stimulated cell proliferation 6-fold in hyperplastic foci. In conclusion, DR lowered IGF-I levels, thereby favoring apoptosis over cell proliferation and ultimately slowing tumor progression. This is the first mechanistic study demonstrating that IGF-I supplementation abrogates the protective effect of DR on neoplastic progression.\",\n \"title\": \"Dietary restriction reduces insulin-like growth factor I levels, which modulates apoptosis, cell proliferation, and tumor progression in p53-defici...\"\n },\n {\n \"docid\": \"MED-2482\",\n \"text\": \"Previous studies have suggested that probiotic administration may have therapeutic and/or preventive effects on atopic dermatitis in infants; however, its role in allergic airway diseases remains controversial. To determine whether daily supplementation with specific Lactobacillus gasseri A5 for 8 weeks can improve the clinical symptoms and immunoregulatory changes in school children suffering from asthma and allergic rhinitis (AR). We conducted a randomized, double-blind, placebo-controlled study on school children (age, 6-12 years) with asthma and AR. The eligible study subjects received either L. gasseri A5 (n = 49) or a placebo (n = 56) daily for 2 months. Pulmonary function tests were performed, and the clinical severity of asthma and AR was evaluated by the attending physicians in the study period. Diary cards with records of the day- and nighttime peak expiratory flow rates (PEFR), symptoms of asthma, and AR scores of the patients were used for measuring the outcome of the treatment. Immunological parameters such as the total IgE and cytokine production by the peripheral blood mononuclear cells (PBMCs) were determined before and after the probiotic treatments. Our results showed the pulmonary function and PEFR increased significantly, and the clinical symptom scores for asthma and AR decreased in the probiotic-treated patients as compared to the controls. Further, there was a significant reduction in the TNF-α, IFN-γ, IL-12, and IL-13 production by the PBMCs following the probiotic treatment. In conclusion, probiotic supplementation may have clinical benefits for school children suffering from allergic airway diseases such as asthma and AR.\",\n \"title\": \"Randomized placebo-controlled trial of lactobacillus on asthmatic children with allergic rhinitis.\"\n },\n {\n \"docid\": \"MED-2206\",\n \"text\": \"Sweet potato is one of the crops selected for NASA's Advanced Life Support Program for potential long-duration lunar/Mars missions. This article presents recipes of products made from sweet potato and determines the consumer acceptability of products containing from 6% to 20% sweet potato on a dry weight basis. These products were developed for use in nutritious and palatable meals for future space explorers. Sensory evaluation (appearance/color, aroma, texture, flavor/taste, and overall acceptability) studies were conducted to determine the consumer acceptability of vegetarian products made with sweet potato using panelists at NASA/Johnson Space Center in Houston, TX. None of these products including the controls, contained any ingredient of animal origin with the exception of sweet potato pie. A 9-point hedonic scale (9 being like extremely and 1 being dislike extremely) was used to evaluate 10 products and compare them to similar commercially available products used as controls. The products tested were pancakes, waffles, tortillas, bread, pie, pound cake, pasta, vegetable patties, doughnuts, and pretzels. All of the products were either liked moderately or liked slightly with the exception of the sweet potato vegetable patties, which were neither liked nor disliked. Mean comparisons of sensory scores of sweet potato recipes and their controls were accomplished by using the Student t-test. Because of their nutritional adequacy and consumer acceptability, these products are being recommended to NASA's Advanced Life Support Program for inclusion in a vegetarian menu plan designed for lunar/Mars space missions.\",\n \"title\": \"Consumer acceptance of vegetarian sweet potato products intended for space missions.\"\n },\n {\n \"docid\": \"MED-2449\",\n \"text\": \"BACKGROUND: Recently, some common foods in daily life have been found to have anti-allergic effects. We have reported that tomato extract (TE) could possibly inhibit histamine release and mouse ear-swelling responses. Moreover, it is reported that TE could relieve the symptoms for Japanese cedar pollinosis. METHODS: To evaluate the anti-allergic effect of TE, we performed a randomized, double-blind, placebo-controlled study in 33 patients with perennial allergic rhinitis (PAR) using oral administration of TE (360 mg per day) or placebo for 8 weeks. RESULTS: We found that the sneezing score significantly decreased in the TE group at the end of the trial compared to the beginning (P < 0.05). There were decreasing tendencies of rhinorrhea and nasal obstruction in the TE group. The patients' quality of life was significantly improved in the TE group after 8 weeks of treatment (P < 0.05), but not in placebo group. A significant improvement in total symptom scores, combining sneezing, rhinorrhea and nasal obstruction, was observed after oral administration of TE for 8 weeks (P < 0.01). The safety of TE treatment was confirmed by laboratory tests and inspection of general conditions. CONCLUSIONS: TE can be expected to safely improve the nasal symptoms of PAR.\",\n \"title\": \"An evaluation of the clinical efficacy of tomato extract for perennial allergic rhinitis.\"\n },\n {\n \"docid\": \"MED-4514\",\n \"text\": \"Background Data on the long-term association between low-carbohydrate diets and mortality are sparse. Objective To examine the association of low-carbohydrate diets with mortality during 26 years of follow-up in women and 20 years in men. Design A prospective cohort study of women and men, followed from 1980 (women) or 1986 (men) until 2006. Low-carbohydrate diets, either animal-based (emphasizing animal sources of fat and protein), or vegetable-based (emphasizing vegetable sources of fat and protein) were computed from multiple validated food frequency questionnaire assessed during follow-up. Setting Nurses' Health Study and Health Professionals' Follow-up Study Participants 85,168 women (aged 34-59 years at baseline) and 44,548 men (aged 40-75 years at baseline) without heart disease, cancer, or diabetes. Measurement Investigator documented 12,555 deaths (2,458 cardiovascular, 5,780 cancer) in women and 8,678 deaths (2,746 cardiovascular, 2,960 cancer) in men. Results The overall low-carbohydrate score was associated with a modest increase in overall mortality in pooled analysis (Hazard Ratio, HR, comparing extreme deciles=1.12 (95% CI=1.01-1.24, p-trend=0.14). The animal low-carbohydrate score was associated with a higher all-cause mortality (pooled HR comparing extreme deciles=1.23, 95% CI=1.11-1.37, p-trend=0.05), cardiovascular mortality (corresponding HR=1.14, 95% CI=1.01-1.29, p-trend=0.029), and cancer mortality (corresponding HR=1.28, 95% CI 1.02-1.60, p for trend = 0.09). In contrast, a higher vegetable low-carbohydrate score was associated with lower all-cause (HR=0.80, 95% CI=0.75-0.85, p-trend<0.001) and cardiovascular mortality (HR=0.77, 95% CI=0.68-0.87, p-trend<0.001). Limitations Diet and lifestyle characteristics were assessed with some degree of error, however, sensitivity analyses indicated that results were not unlikely to be substantially affected by residual or confounding or an unmeasured confounder. In addition, participants were not a representative sample of the U.S. population. Conclusion A low-carbohydrate diet based on animal sources was associated with higher all-cause mortality in both men and women, whereas a vegetable-based low-carbohydrate diet was associated with lower all-cause and cardiovascular disease mortality rates. Primary funding source NIH grants CA87969, HL60712, and CA95589\",\n \"title\": \"Low-carbohydrate diets and all-cause and cause-specific mortality: Two cohort Studies\"\n },\n {\n \"docid\": \"MED-5204\",\n \"text\": \"It is generally accepted that carbohydrate fermentation results in beneficial effects for the host because of the generation of short chain fatty acids, whereas protein fermentation is considered detrimental for the host's health. Protein fermentation mainly occurs in the distal colon, when carbohydrates get depleted and results in the production of potentially toxic metabolites such as ammonia, amines, phenols and sulfides. However, the effectivity of these metabolites has been established mainly in in vitro studies. In addition, some important bowel diseases such as colorectal cancer (CRC) and ulcerative colitis appear most often in the distal colon, which is the primary site of protein fermentation. Finally, epidemiological studies revealed that diets rich in meat are associated with the prevalence of CRC, as is the case in Western society. Importantly, meat intake not only increases fermentation of proteins but also induces increased intake of fat, heme and heterocyclic amines, which may also play a role in the development of CRC. Despite these indications, the relationship between gut health and protein fermentation has not been thoroughly investigated. In this review, the existing evidence about the potential toxicity of protein fermentation from in vitro animal and human studies will be summarized. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.\",\n \"title\": \"Relevance of protein fermentation to gut health.\"\n },\n {\n \"docid\": \"MED-2294\",\n \"text\": \"The number of studies comparing nutritional quality of restrictive diets is limited. Data on vegan subjects are especially lacking. It was the aim of the present study to compare the quality and the contributing components of vegan, vegetarian, semi-vegetarian, pesco-vegetarian and omnivorous diets. Dietary intake was estimated using a cross-sectional online survey with a 52-items food frequency questionnaire (FFQ). Healthy Eating Index 2010 (HEI-2010) and the Mediterranean Diet Score (MDS) were calculated as indicators for diet quality. After analysis of the diet questionnaire and the FFQ, 1475 participants were classified as vegans (n = 104), vegetarians (n = 573), semi-vegetarians (n = 498), pesco-vegetarians (n = 145), and omnivores (n = 155). The most restricted diet, i.e., the vegan diet, had the lowest total energy intake, better fat intake profile, lowest protein and highest dietary fiber intake in contrast to the omnivorous diet. Calcium intake was lowest for the vegans and below national dietary recommendations. The vegan diet received the highest index values and the omnivorous the lowest for HEI-2010 and MDS. Typical aspects of a vegan diet (high fruit and vegetable intake, low sodium intake, and low intake of saturated fat) contributed substantially to the total score, independent of the indexing system used. The score for the more prudent diets (vegetarians, semi-vegetarians and pesco-vegetarians) differed as a function of the used indexing system but they were mostly better in terms of nutrient quality than the omnivores.\",\n \"title\": \"Comparison of Nutritional Quality of the Vegan, Vegetarian, Semi-Vegetarian, Pesco-Vegetarian and Omnivorous Diet\"\n },\n {\n \"docid\": \"MED-2335\",\n \"text\": \"Xenohormesis is a biological principle that explains how environmentally stressed plants produce bioactive compounds that can confer stress resistance and survival benefits to animals that consume them. Animals can piggyback off products of plants' sophisticated stress response which has evolved as a result of their stationary lifestyle. Factors eliciting the plant stress response can judiciously be employed to maximize yield of health-promoting plant compounds. The xenohormetic plant compounds can, when ingested, improve longevity and fitness by activating the animal's cellular stress response and can be applied in drug discovery, drug production, and nutritional enhancement of diet.\",\n \"title\": \"Xenohormesis: health benefits from an eon of plant stress response evolution\"\n },\n {\n \"docid\": \"MED-2351\",\n \"text\": \"Anti-Gal is a natural Ab abundantly produced in humans. It interacts specifically with the carbohydrate epitope Gal alpha 1-3Gal beta 1-4GlcNAc-R (termed the alpha-galactosyl epitope). This epitope is expressed in large amounts on thyrocytes of nonprimate mammals, but not of humans. We have previously found that binding of anti-Gal to alpha-galactosyl epitopes on porcine thyrocytes results in stimulatory effects similar to those exerted by thyroid-stimulating hormone (thyrotropin). In the present study, we tested the hypothesis that anti-Gal may contribute to Graves' disease (GD) pathogenesis by stimulation of the thyrocytes of patients with this autoimmune disorder. Anti-Gal binding and stimulatory effects were assessed in primary thyrocyte cultures. Anti-Gal specifically bound to GD thyrocytes and induced an increase in cAMP synthesis, 125I uptake, and DNA synthesis in these cells. Furthermore, the stimulatory effects of autologous sera on GD thyrocytes were greatly reduced after specific depletion of anti-Gal from these sera. No binding and no stimulatory effects of anti-Gal were observed, however, with normal human thyrocytes and with thyrocytes from thyrotoxic patients who lack thyroid-stimulating Igs or thyrotropin binding inhibiting Igs. These in vitro stimulatory effects of anti-Gal on GD thyrocytes suggest that this natural Ab may contribute to the in vivo continuous stimulation of thyrocytes in GD patients. The possibility that anti-Gal may stimulate GD thyrocytes via interaction with aberrantly expressed alpha-galactosyl epitopes on the thyroid-stimulating hormone receptor is discussed.\",\n \"title\": \"Specific stimulation of Graves' disease thyrocytes by the natural anti-Gal antibody from normal and autologous serum.\"\n },\n {\n \"docid\": \"MED-3355\",\n \"text\": \"OBJECTIVE: To evaluate the effects of a high-fat and low-fat diet on taste sensitivity to oleic acid (C18:1) in lean and overweight/obese (OW/OB) subjects. DESIGN: Randomized cross-over dietary intervention involving the consumption of a high-fat (>45% fat) and low-fat (<20% fat) diet, both consumed over a 4-week period. SUBJECTS: A total of 19 lean, mean age 33±13 years, mean body mass index (BMI) 23.2±2.2 kg m(-2) and 12 OW/OB, mean age 39.5±3 years, mean BMI 28±2.6 kg m(-2), subjects participated in the study, which measured taste thresholds for C18:1, fat perception and hedonic ratings for regular (RF) and lowered-fat (LF) foods before, and following consumption of a high- and low-fat diet. RESULTS: Consumption of the low-fat diet increased taste sensitivity to C18:1 among lean and OW/OB subjects (P<0.05) and increased the subjects ability to perceive small differences in the fat content of custard (P=0.05). Consumption of the high-fat diet significantly decreased taste sensitivity to C18:1 among lean subjects (P<0.05), with no change in sensitivity among OW/OB persons (P=0.609). The hedonic ratings for several RF and LF foods differed following the diets. CONCLUSION: Alterations in the fat content of the diet modulated taste sensitivity to C18:1 among lean subjects, which was increased following a 4-week period of fat restriction and attenuated following the high-fat diet. The failure of the high-fat diet to alter fatty acid taste thresholds among OW/OB subjects suggests that these individuals were 'adapted' to high-fat exposure, perhaps because of differences in habitual fat consumption. Taken together, these data suggest that excessive dietary fat attenuates nutrient sensing epithelia response in the oral cavity, which could be associated with changes in diet and weight status.\",\n \"title\": \"Recent fat intake modulates fat taste sensitivity in lean and overweight subjects.\"\n },\n {\n \"docid\": \"MED-4206\",\n \"text\": \"Vegetarian diets are rich in antioxidant phytochemicals. However, they may not act as antioxidants in vivo, and yet still have important signaling and regulatory functions. Some may act as pro-oxidants, modulating cellular redox tone and oxidizing redox sensitive sites. In this review, evidence for health benefits of vegetarian diets is presented from different perspectives: epidemiological, biomarker, evolutionary, and public health, as well as antioxidant. From the perspective of molecular connections between diet and health, evidence of a role for plasma ascorbic acid as a biomarker for future disease risk is presented. Basic concepts of redox-based cell signaling are presented, and effects of antioxidant phytochemicals on signaling, especially via redox tone, sulfur switches and the Antioxidant Response Element (ARE), are explored. Sufficient scientific evidence exists for public health policy to promote a plant-rich diet for health promotion. This does not need to wait for science to provide all the answers as to why and how. However, action and interplay of dietary antioxidants in the nonequilibrium systems that control redox balance, cell signaling, and cell function provide rich ground for research to advance understanding of orthomolecular nutrition and provide science-based evidence to advance public health in our aging population.\",\n \"title\": \"Vegetarian diets and public health: biomarker and redox connections.\"\n },\n {\n \"docid\": \"MED-3772\",\n \"text\": \"A clinical link exists between severe dehydration and cognitive performance. Using rapid and severe water loss induced either by intense exercise and/or heat stress, initial studies suggested there were alterations in short-term memory and cognitive function related to vision, but more recent studies have not all confirmed these data. Some studies argue that water loss is not responsible for the observations made, and studies compensating water losses have failed to prevent the symptoms. Studies in children have suggested that drinking extra water helps cognitive performance, but these data rely on a small number of children. In older adults (mean age around 60) the data are not strong enough to support a relationship between mild dehydration and cognitive function. Data on frail elderly and demented people are lacking. Methodological heterogeneity in these studies are such that the relationship between mild dehydration and cognitive performance cannot be supported.\",\n \"title\": \"Hydration and cognitive performance.\"\n },\n {\n \"docid\": \"MED-5293\",\n \"text\": \"Summary Background Quantification of the disease burden caused by different risks informs prevention by providing an account of health loss different to that provided by a disease-by-disease analysis. No complete revision of global disease burden caused by risk factors has been done since a comparative risk assessment in 2000, and no previous analysis has assessed changes in burden attributable to risk factors over time. Methods We estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010. We estimated exposure distributions for each year, region, sex, and age group, and relative risks per unit of exposure by systematically reviewing and synthesising published and unpublished data. We used these estimates, together with estimates of cause-specific deaths and DALYs from the Global Burden of Disease Study 2010, to calculate the burden attributable to each risk factor exposure compared with the theoretical-minimum-risk exposure. We incorporated uncertainty in disease burden, relative risks, and exposures into our estimates of attributable burden. Findings In 2010, the three leading risk factors for global disease burden were high blood pressure (7·0% [95% uncertainty interval 6·2–7·7] of global DALYs), tobacco smoking including second-hand smoke (6·3% [5·5–7·0]), and alcohol use (5·5% [5·0–5·9]). In 1990, the leading risks were childhood underweight (7·9% [6·8–9·4]), household air pollution from solid fuels (HAP; 7·0% [5·6–8·3]), and tobacco smoking including second-hand smoke (6·1% [5·4–6·8]). Dietary risk factors and physical inactivity collectively accounted for 10·0% (95% UI 9·2–10·8) of global DALYs in 2010, with the most prominent dietary risks being diets low in fruits and those high in sodium. Several risks that primarily affect childhood communicable diseases, including unimproved water and sanitation and childhood micronutrient deficiencies, fell in rank between 1990 and 2010, with unimproved water we and sanitation accounting for 0·9% (0·4–1·6) of global DALYs in 2010. However, in most of sub-Saharan Africa childhood underweight, HAP, and non-exclusive and discontinued breastfeeding were the leading risks in 2010, while HAP was the leading risk in south Asia. The leading risk factor in Eastern Europe, most of Latin America, and southern sub-Saharan Africa in 2010 was alcohol use; in most of Asia, North Africa and Middle East, and central Europe it was high blood pressure. Despite declines, tobacco smoking including second-hand smoke remained the leading risk in high-income north America and western Europe. High body-mass index has increased globally and it is the leading risk in Australasia and southern Latin America, and also ranks high in other high-income regions, North Africa and Middle East, and Oceania. Interpretation Worldwide, the contribution of different risk factors to disease burden has changed substantially, with a shift away from risks for communicable diseases in children towards those for non-communicable diseases in adults. These changes are related to the ageing population, decreased mortality among children younger than 5 years, changes in cause-of-death composition, and changes in risk factor exposures. New evidence has led to changes in the magnitude of key risks including unimproved water and sanitation, vitamin A and zinc deficiencies, and ambient particulate matter pollution. The extent to which the epidemiological shift has occurred and what the leading risks currently are varies greatly across regions. In much of sub-Saharan Africa, the leading risks are still those associated with poverty and those that affect children. Funding Bill & Melinda Gates Foundation.\",\n \"title\": \"A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010\"\n },\n {\n \"docid\": \"MED-2274\",\n \"text\": \"Objective To study the relation between cherry intake and the risk of recurrent gout attacks among individuals with gout. Methods We conducted a case-crossover study to examine associations of a set of putative risk factors with recurrent gout attacks. Individuals with gout were prospectively recruited and followed online for one year. Participants were asked about the following information when experiencing a gout attack: the onset date of the gout attack, symptoms and signs, medications (including anti-gout medications), and potential risk factors (including daily intake of cherries and cherry extract) during the 2-day period prior to the gout attack. We assessed the same exposure information over 2-day control periods. We estimated the risk of recurrent gout attacks related to cherry intake using conditional logistic regression. Results Our study included 633 individuals with gout. Cherry intake over a 2-day period was associated with a 35% lower risk of gout attacks compared with no intake (multivariate odds ratio [OR] = 0.65, 95% CI: 0.50-0.85). Cherry extract intake showed a similar inverse association (multivariate OR=0.55, 95% CI: 0.30-0.98). The effect of cherry intake persisted across subgroups by sex, obesity status, purine intake, alcohol use, diuretic use, and use of anti-gout medications. When cherry intake was combined with allopurinol use, the risk of gout attacks was 75% lower than periods without either exposure (OR=0.25, 95% CI: 0.15-0.42). Conclusions These findings suggest that cherry intake is associated with a lower risk of gout attacks.\",\n \"title\": \"Cherry Consumption and the Risk of Recurrent Gout Attacks\"\n },\n {\n \"docid\": \"MED-3312\",\n \"text\": \"BACKGROUND: Heavy alcohol consumption, viral hepatitis, and diabetes are risk factors for hepatocellular carcinoma (HCC). However, to the authors' knowledge, the information concerning their interaction effect in patients with risk of HCC is sparse. METHODS: A population-based, case-control study of HCC was conducted during 1984-2002. The study involved 295 HCC cases and 435 age-, gender-, and race-matched control subjects among Hispanic and non-Hispanic whites and blacks in Los Angeles County, California. Lifestyle risk factors were ascertained through in-person interviews. Infections with the hepatitis B and C (HCV) viruses were determined using their serologic markers. RESULTS: Fourteen HCC cases but no control subjects tested positive for the hepatitis B surface antigen. Seropositivity for antibodies to HCV was associated with an odds ratio (OR) of 125 (95% confidence interval [95% CI], 17-909) for HCC, whereas seropositivity for antibodies to the hepatitis B core antigen was related to an OR of 2.9 (95% CI, 1.7-5.0). Heavy alcohol consumption and cigarette smoking were found to be independently associated with a statistically significant two to threefold increase in risk of HCC after adjustment for hepatitis B and C serology. Subjects with a history of diabetes had an OR of 2.7 (95% CI, 1.6-4.3) for HCC compared with nondiabetic subjects. A synergistic interaction on HCC risk was observed between heavy alcohol consumption and diabetes (OR = 4.2; 95% CI, 2.6-5.8), heavy alcohol consumption and viral hepatitis (OR = 5.5; 95% CI, 3.9-7.0), or between diabetes and viral hepatitis (OR = 4.8; 95% CI, 2.7-6.9). CONCLUSIONS: Heavy alcohol consumption, diabetes, and viral hepatitis were found to exert independent and synergistic effects on risk of HCC in U.S. blacks and whites. Copyright 2004 American Cancer Society.\",\n \"title\": \"Synergism of alcohol, diabetes, and viral hepatitis on the risk of hepatocellular carcinoma in blacks and whites in the U.S.\"\n },\n {\n \"docid\": \"MED-3123\",\n \"text\": \"DietCompLyf is a multi-centre prospective study designed to investigate associations between phytoestrogens - naturally occurring plant compounds with oestrogenic properties - and other diet and lifestyle factors with breast cancer recurrence and survival. 3159 women with grades I-III breast cancer were recruited 9-15 months post-diagnosis from 56 UK hospitals. Detailed information on clinico-pathological, diet, lifestyle and quality of life is collected annually up to 5 years. Biological samples have also been collected as a resource for subsequent evaluation. The characteristics of the patients and associations between pre-diagnosis intake of phytoestrogens (isoflavones and lignans; assessed using the EPIC-Norfolk UK 130 question food frequency questionnaire) and breast cancer (i) risk factors and (ii) prognostic factors are described for 1797 women who had complete data for all covariates and phytoestrogens of interest. Isoflavone intakes were higher in the patients who were younger at diagnosis, in the non-smokers, those who had breast-fed and those who took supplements. Lignan intakes were higher in patients with a higher age at diagnosis, in ex-smokers, those who had breast-fed, who took supplements, had a lower BMI at diagnosis, lower age at menarche and were nulliparous. No significant associations between pre-diagnosis phytoestrogen intake and factors associated with improved breast cancer prognosis were observed. The potential for further exploration of the relationship between phytoestrogens and breast cancer recurrence and survival, and for the establishment of evidence to improve dietary and lifestyle advice offered to patients following breast cancer diagnosis using DietCompLyf data is discussed. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.\",\n \"title\": \"The DietCompLyf study: a prospective cohort study of breast cancer survival and phytoestrogen consumption.\"\n },\n {\n \"docid\": \"MED-2827\",\n \"text\": \"Alternative and complementary therapeutic approaches, such as the use of a wide array of herbal, nutritional, and physical manipulations, are becoming popular for relieving symptoms of osteoarthritis (OA). The present study evaluated the efficacy of soy protein (SP) supplementation in relieving the pain and discomfort associated with OA. One hundred and thirty-five free-living individuals (64 men and 71 women) with diagnosed OA or with self-reported chronic knee joint pain not attributed to injury or rheumatoid arthritis were recruited for this double-blind, placebo-controlled, parallel design study. Study participants were assigned randomly to consume 40 g of either supplemental SP or milk-based protein (MP) daily for 3 months. Pain, knee range of motion, and overall physical activity were evaluated prior to the start of treatment and monthly thereafter. Serum levels of glycoprotein 39 (YKL-40), a marker of cartilage degradation, and insulin-like growth factor-I (IGF-I), a growth factor associated with cartilage synthesis, were assessed at baseline and at the end of the study. Overall, SP improved OA-associated symptoms such as range of motion and several factors associated with pain and quality of life in comparison to MP. However, these beneficial effects were mainly due to the effect of SP in men rather than women. Biochemical markers of cartilage metabolism further support the efficacy of SP in men as indicated by a significant increase in serum level of IGF-I and a significant decrease in serum level of YKL-40 compared to MP. This study is the first to provide evidence of possible beneficial effects of SP in the management of OA. Examining and verifying the long-term effects of SP on improving symptoms of OA, particularly in men, is warranted.\",\n \"title\": \"Soy protein may alleviate osteoarthritis symptoms.\"\n },\n {\n \"docid\": \"MED-2458\",\n \"text\": \"BACKGROUND: Antioxidant-rich diets are associated with reduced asthma prevalence in epidemiologic studies. We previously showed that short-term manipulation of antioxidant defenses leads to changes in asthma outcomes. OBJECTIVE: The objective was to investigate the effects of a high-antioxidant diet compared with those of a low-antioxidant diet, with or without lycopene supplementation, in asthma. DESIGN: Asthmatic adults (n = 137) were randomly assigned to a high-antioxidant diet (5 servings of vegetables and 2 servings of fruit daily; n = 46) or a low-antioxidant diet (≤2 servings of vegetables and 1 serving of fruit daily; n = 91) for 14 d and then commenced a parallel, randomized, controlled supplementation trial. Subjects who consumed the high-antioxidant diet received placebo. Subjects who consumed the low-antioxidant diet received placebo or tomato extract (45 mg lycopene/d). The intervention continued until week 14 or until an exacerbation occurred. RESULTS: After 14 d, subjects consuming the low-antioxidant diet had a lower percentage predicted forced expiratory volume in 1 s and percentage predicted forced vital capacity than did those consuming the high-antioxidant diet. Subjects in the low-antioxidant diet group had increased plasma C-reactive protein at week 14. At the end of the trial, time to exacerbation was greater in the high-antioxidant than in the low-antioxidant diet group, and the low-antioxidant diet group was 2.26 (95% CI: 1.04, 4.91; P = 0.039) times as likely to exacerbate. Of the subjects in the low-antioxidant diet group, no difference in airway or systemic inflammation or clinical outcomes was observed between the groups that consumed the tomato extract and those who consumed placebo. CONCLUSIONS: Modifying the dietary intake of carotenoids alters clinical asthma outcomes. Improvements were evident only after increased fruit and vegetable intake, which suggests that whole-food interventions are most effective. This trial was registered at http://www.actr.org.au as ACTRN012606000286549.\",\n \"title\": \"Manipulating antioxidant intake in asthma: a randomized controlled trial.\"\n },\n {\n \"docid\": \"MED-4551\",\n \"text\": \"Interest has increased in the possibility that maternal dietary intake during pregnancy might influence the development of allergic disorders in children. The present prospective study examined the association of maternal intake of selected foods high in fatty acids and specific types of fatty acids during pregnancy with the risk of suspected atopic eczema among Japanese infants aged 3-4 months. Subjects were 771 mother-child pairs. Information on maternal dietary intake during pregnancy was assessed with a validated self-administered diet history questionnaire. The term 'suspected atopic eczema' was used to define an outcome based on results of our questionnaire completed by mothers 3-4 months postpartum. The risk of suspected atopic eczema was 8.4% (n = 65). Higher maternal intake of meat during pregnancy was significantly associated with an increased risk of suspected atopic eczema in the offspring: the multivariate odds ratio (OR) for the highest vs. lowest quartile was 2.59 [95% confidence interval (CI): 1.15-6.17, p for trend = 0.01]. The positive association was strengthened when the definition of the outcome was confined to a definite physician's diagnosis of atopic eczema (n = 35): the multivariate OR between extreme quartiles was 3.53 (95% CI: 1.19-12.23, p for trend = 0.02). No material exposure-response relationships were observed between maternal intake of eggs, dairy products, fish, total fat, saturated fatty acids, monounsaturated fatty acids, n-3 polyunsaturated fatty acids, alpha-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, n-6 polyunsaturated fatty acids, linoleic acid, arachidonic acid and cholesterol and the ratio of n-3 to n-6 polyunsaturated fatty acid consumption and the risk of suspected atopic eczema. Higher maternal meat intake may increase the risk of infantile atopic eczema, whereas we found no evidence that maternal intake of fish and n-3 polyunsaturated fatty acids are preventive against infantile atopic eczema. (c) 2009 John Wiley & Sons A/S\",\n \"title\": \"Maternal meat and fat consumption during pregnancy and suspected atopic eczema in Japanese infants aged 3-4 months: the Osaka Maternal and Child He...\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"MED-1807","text":"BACKGROUND: As protein is considered to increase thermogenesis and satiety more than other macronutrients, it may have beneficial effects on prevention of weight gain and weight maintenance. OBJECTIVE: The objective of this study is to assess the association between the amount and type of dietary protein, and subsequent changes in weight and waist circumference (WC). METHODS: 89,432 men and women from five countries participating in European Prospective Investigation into Cancer and Nutrition (EPIC) were followed for a mean of 6.5 years. Associations between the intake of protein or subgroups of protein (from animal and plant sources) and changes in weight (g per year) or WC (cm per year) were investigated using gender and centre-specific multiple regression analyses. Adjustments were made for other baseline dietary factors, baseline anthropometrics, demographic and lifestyle factors and follow-up time. We used random effect meta-analyses to obtain pooled estimates across centres. RESULTS: Higher intake of total protein, and protein from animal sources was associated with subsequent weight gain for both genders, strongest among women, and the association was mainly attributable to protein from red and processed meat and poultry rather than from fish and dairy sources. There was no overall association between intake of plant protein and subsequent changes in weight. No clear overall associations between intakes of total protein or any of the subgroups and changes in WC were present. The associations showed some heterogeneity between centres, but pooling of estimates was still considered justified. CONCLUSION: A high intake of protein was not found associated with lower weight or waist gain in this observational study. In contrast, protein from food items of animal origin, especially meat and poultry, seemed to be positively associated with long-term weight gain. There were no clear associations for waist changes.","title":"Intake of total, animal and plant protein and subsequent changes in weight or waist circumference in European men and women: the Diogenes project."},{"docid":"MED-1446","text":"Literature on the association of protein intake with body weight is inconsistent. Little is known about the relation of long-term protein intake to obesity. This study aimed to determine the association between protein intake and obesity. A cohort of 1,730 employed white men ages 40–55 years from the Chicago Western Electric Study was followed from 1958 to 1966. Diet was assessed twice with Burke’s comprehensive diet history method, at two baseline examinations; height, weight, and other covariates were measured annually by trained interviewers. Generalized estimating equation (GEE) was used to examine the relation of baseline total, animal, and vegetable protein intake to likelihood of being overweight or obese at sequential annual examinations. Dietary animal protein was positively related to overweight and obesity over seven years of follow up. With adjustment for potential confounders (age, education, cigarette smoking, alcohol intake, energy, carbohydrate and saturated fat intake, and history of diabetes or other chronic disease), the odds ratios (95% confidence intervals) for obesity were 4.62 (2.68–7.98, p for trend<0.01) for participants in the highest compared to the lowest quartile of animal protein and 0.58 (0.36, 0.95, p for trend=0.053) for those in the highest quartile of vegetable protein intake. A statistically significant, positive association was seen between animal protein intake and obesity; those in higher quartiles of vegetable protein intake had lower odds of being obese. These results indicate that animal and vegetable protein may relate differently to occurrence of obesity in the long run.","title":"Longitudinal association between animal and vegetable protein intake and obesity among adult males in the United States: the Chicago Western Electric Study"},{"docid":"MED-1869","text":"Observational and clinical studies suggest that high protein intake, particularly protein from plant sources, might reduce blood pressure (BP). To examine the association of dietary protein with BP, we analysed data from PREMIER, an 18-month clinical trial (n=810) that examined the effects of two multi-component lifestyle modifications on BP. We examined the association of protein intake with BP, and in particular the independent relationship of plant and animal protein with BP. Multivariable linear regression analyses were performed with both cross-sectional and longitudinal data. Dietary plant protein was inversely associated with both systolic and diastolic BP in cross-sectional analyses at the 6-month follow-up (P=0.0045 and 0.0096, respectively). Fruit and vegetable intake was also inversely associated with both systolic and diastolic BP cross-sectionally at 6 months (P=0.0003 and 0.0157, respectively). In longitudinal analyses, a high intake of plant protein at 6 months was marginally associated with a reduction of both systolic and diastolic BP from baseline to 6 months only (P=0.0797 and 0.0866, respectively), independent of change in body weight and waist circumference. Furthermore, increased intake of plant protein, and fruits and vegetables was significantly associated with a lower risk of hypertension at 6 but not at 18 months. Results of this study indicate that plant protein had a beneficial effect on BP and was associated with a lower risk of hypertension at 6 months. Our data, in conjunction with other research, suggest that an increased intake of plant protein may be useful as a means to prevent and treat hypertension.","title":"The relationship between dietary protein intake and blood pressure: results from the PREMIER study."},{"docid":"MED-1281","text":"The calcium ion (Ca2+) is a ubiquitous second messenger that is crucial for the regulation of a wide variety of cellular processes. The diverse transient signals transduced by Ca2+ are mediated by intracellular Ca2+-binding proteins, also known as Ca2+ sensors. A key obstacle to studying many Ca2+-sensing proteins is the difficulty in identifying the numerous downstream target interactions that respond to Ca2+-induced conformational changes. Among a number of Ca2+ sensors in the eukaryotic cell, calmodulin (CaM) is the most widespread and the best studied. Employing the mRNA display technique, we have scanned the human proteome for CaM-binding proteins and have identified and characterized a large number of both known and previously uncharacterized proteins that interact with CaM in a Ca2+-dependent manner. The interactions of several identified proteins with Ca2+/CaM were confirmed by using pull-down assays and coimmunoprecipitation. Many of the CaM-binding proteins identified belong to protein families such as the DEAD/H box proteins, ribosomal proteins, proteasome 26S subunits, and deubiquitinating enzymes, suggesting the possible involvement of Ca2+/CaM in different signaling pathways. The selection method described herein could be used to identify the binding partners of other calcium sensors on the proteome-wide scale.","title":"Scanning the human proteome for calmodulin-binding proteins"},{"docid":"MED-5199","text":"Studies attempting to evaluate protein assimilation in humans have hitherto relied on either ileostomy subjects or intubation techniques. The availability of stable isotope-labeled protein allowed us to determine the amount and fate of dietary protein escaping digestion and absorption in the small intestine of healthy volunteers using noninvasive tracer techniques. Ten healthy volunteers were studied once after ingestion of a cooked test meal, consisting of 25 g of (13)C-, (15)N-, and (2)H-labeled egg protein, and once after ingestion of the same but raw meal. Amounts of 5.73% and 35.10% (P < 0.005) of cooked and raw test meal, respectively, escaped digestion and absorption in the small intestine. A significantly higher percentage of the malabsorbed raw egg protein was recovered in urine as fermentation metabolites. These results 1) confirm that substantial amounts of even easily digestible proteins may escape assimilation in healthy volunteers and 2) further support the hypothesis that the metabolic fate of protein in the colon is affected by the amount of protein made available.","title":"Amount and fate of egg protein escaping assimilation in the small intestine of humans."},{"docid":"MED-1425","text":"We examined the correlation between the incidence of Crohn disease and dietary change in a relatively homogeneous Japanese population. The incidence and daily intake of each dietary component were compared annually from 1966 to 1985. The univariate analysis showed that the increased incidence of Crohn disease was strongly (P < 0.001) correlated with increased dietary intake of total fat (r = 0.919). animal fat (r = 0.880), n-6 polyunsaturated fatty acids (r = 0.883), animal protein (r = 0.908), milk protein (r = 0.924), and the ratio of n-6 to n-3 fatty acid intake (r = 0.792). It was less correlated with intake of total protein (r = 0.482, P < 0.05), was not correlated with intake of fish protein (r = 0.055, P > 0.1), and was inversely correlated with intake of vegetable protein (r = -0.941, P < 0.001). The multivariate analysis showed that increased intake of animal protein was the strongest independent factor with a weaker second factor, an increased ration of n-6 to n-3 polyunsaturated fatty acids. The present study in association with reported clinical studies suggests that increased dietary intake of animal protein and n-6 polyunsaturated fatty acids with less n-3 polyunsaturated fatty acids may contribute to the development of Crohn disease.","title":"Epidemiologic analysis of Crohn disease in Japan: increased dietary intake of n-6 polyunsaturated fatty acids and animal protein relates to the inc..."},{"docid":"MED-2943","text":"BACKGROUND: Western diets, which typically contain large amounts of energy-dense processed foods, together with a sedentary lifestyle are associated with increased cardiometabolic risk. We evaluated the long-term effects of consuming a low-calorie low-protein vegan diet or performing regular endurance exercise on cardiometabolic risk factors. METHODS: In this cross-sectional study, cardiometabolic risk factors were evaluated in 21 sedentary subjects, who had been on a low-calorie low-protein raw vegan diet for 4.4 +/- 2.8 years, (mean age, 53.1 +/- 11 yrs), 21 body mass index (BMI)-matched endurance runners consuming Western diets, and 21 age- and gender-matched sedentary subjects, consuming Western diets. RESULTS: BMI was lower in the low-calorie low-protein vegan diet (21.3 +/- 3.1 kg/m(2)) and endurance runner (21.1 +/- 1.6 kg/m(2)) groups than in the sedentary Western diet group (26.5 +/- 2.7 kg/m(2)) (p < 0.005). Plasma concentrations of lipids, lipoproteins, glucose, insulin, C-reactive protein, blood pressure (BP), and carotid artery intima-media thickness were lower in the low-calorie low-protein vegan diet and runner groups than in the Western diet group (all p < 0.05). Both systolic and diastolic BP were lower in the low-calorie low-protein vegan diet group (104 +/- 15 and 62 +/- 11 mm Hg) than in BMI-matched endurance runners (122 +/- 13 and 72 +/- 9 mmHg) and Western diet group (132 +/- 14 and 79 +/- 8 mm Hg) (p < 0.001); BP values were directly associated with sodium intake and inversely associated with potassium and fiber intake. CONCLUSIONS: Long-term consumption of a low-calorie low-protein vegan diet or regular endurance exercise training is associated with low cardiometabolic risk. Moreover, our data suggest that specific components of a low-calorie low-protein vegan diet provide additional beneficial effects on blood pressure.","title":"Long-term low-calorie low-protein vegan diet and endurance exercise are associated with low cardiometabolic risk."},{"docid":"MED-4509","text":"Hypercholesterolemia is a major modifiable risk factor for cardiovascular disease. Some, but not all, studies have shown that soy protein intake decreases total and low-density lipoprotein cholesterol and triglycerides and increases high-density lipoprotein cholesterol. The objective of this meta-analysis was to examine the effect of soy protein supplementation on serum lipid levels in adults. English language articles were retrieved by searching MEDLINE (1966 to February 2005) and the bibliographies of the retrieved articles. A total of 41 randomized controlled trials in which isolated soy protein supplementation was the only intervention and the net changes in serum lipids during intervention were reported. Information on study design, sample size, participant characteristics, intervention, follow-up duration, and treatment outcomes was independently abstracted using a standardized protocol. Using a random-effects model, data from each study were pooled and weighted by the inverse of their variance. Soy protein supplementation was associated with a significant reduction in mean serum total cholesterol (-5.26 mg/dl, 95% confidence interval [CI] -7.14 to -3.38), low-density lipoprotein cholesterol (-4.25 mg/dl, 95% CI -6.00 to -2.50), and triglycerides (-6.26 mg/dl, 95% CI -9.14 to -3.38) and a significant increase in high-density lipoprotein cholesterol (0.77 mg/dl, 95% CI 0.20 to 1.34). Meta-regression analyses showed a dose-response relation between soy protein and isoflavone supplementation and net changes in serum lipids. These results indicate that soy protein supplementation reduces serum lipids among adults with or without hypercholesterolemia. In conclusion, replacing foods high in saturated fat, trans-saturated fat, and cholesterol with soy protein may have a beneficial effect on coronary risk factors.","title":"A meta-analysis of the effect of soy protein supplementation on serum lipids."},{"docid":"MED-1323","text":"Background: Fat and protein sources may influence whether low-carbohydrate diets are associated with type 2 diabetes (T2D). Objective: The objective was to compare the associations of 3 low-carbohydrate diet scores with incident T2D. Design: A prospective cohort study was conducted in participants from the Health Professionals Follow-Up Study who were free of T2D, cardiovascular disease, or cancer at baseline (n = 40,475) for up to 20 y. Cumulative averages of 3 low-carbohydrate diet scores (high total protein and fat, high animal protein and fat, and high vegetable protein and fat) were calculated every 4 y from food-frequency questionnaires and were associated with incident T2D by using Cox models. Results: We documented 2689 cases of T2D during follow-up. After adjustments for age, smoking, physical activity, coffee intake, alcohol intake, family history of T2D, total energy intake, and body mass index, the score for high animal protein and fat was associated with an increased risk of T2D [top compared with bottom quintile; hazard ratio (HR): 1.37; 95% CI: 1.20, 1.58; P for trend < 0.01]. Adjustment for red and processed meat attenuated this association (HR: 1.11; 95% CI: 0.95, 1.30; P for trend = 0.20). A high score for vegetable protein and fat was not significantly associated with the risk of T2D overall but was inversely associated with T2D in men aged <65 y (HR: 0.78; 95% CI: 0.66, 0.92; P for trend = 0.01, P for interaction = 0.01). Conclusions: A score representing a low-carbohydrate diet high in animal protein and fat was positively associated with the risk of T2D in men. Low-carbohydrate diets should obtain protein and fat from foods other than red and processed meat.","title":"Low-carbohydrate diet scores and risk of type 2 diabetes in men"},{"docid":"MED-4745","text":"Early puberty onset is associated with hormone-related cancers, but whether diet in childhood influences pubertal timing is controversial. We examined the association of protein intake in early and mid-childhood with the ages at take-off of the pubertal growth spurt (ATO), peak height velocity (APHV), and menarche in girls and voice break in boys using data from the longitudinal Dortmund Nutritional and Anthropometric Longitudinally Designed Study. Among participants who provided 3-d weighed dietary records at 12 mo, 18-24 mo, 3-4 y, and 5-6 y, 112 had sufficient anthropometric measurements between 6 and 13 y to allow estimation of ATO. Life-course plots were used to identify critical periods of total, animal, and vegetable protein intake (percentage of total energy intake) for pubertal timing. At these ages, the association between tertiles of protein intake (T1-T3) and the outcomes was investigated using multiple linear regression analysis. A higher total and animal protein intake at 5-6 y was related to an earlier ATO. In the highest tertile of animal protein intake at 5-6 y, ATO occurred 0.6 y earlier than in the lowest [(mean, 95% CI) T1: 9.6, 9.4-9.9 vs. T2: 9.4, 9.1-9.7 vs. T3: 9.0, 8.7-9.3 y; P-trend = 0.003, adjusted for sex, total energy, breast-feeding, birth year, and paternal university degree]. Similar findings were seen for APHV (P-trend = 0.001) and the timing of menarche/voice break (P-trend = 0.02). Conversely, a higher vegetable protein intake at 3-4 and 5-6 y was related to later ATO, APHV, and menarche/voice break (P-trend = 0.02-0.04). These results suggest that animal and vegetable protein intake in mid-childhood might be differentially related to pubertal timing.","title":"Dietary protein intake throughout childhood is associated with the timing of puberty."},{"docid":"MED-1135","text":"The hypothesis that the incidence of calcium stone disease is related to the consumption of animal protein has been examined. Within the male population, recurrent idiopathic stone formers consumed more animal protein than did normal subjects. Single stone formers had animal protein intakes intermediate between those of normal men and those of recurrent stone formers. A high animal protein intake caused a significant increase in the urinary excretion of calcium, oxalate and uric acid, 3 of the 6 main urinary risk factors for calcium stone formation. The overall relative probability of forming stones, calculated from the combination of the 6 main urinary risk factors, was markedly increased by a high animal protein diet. Conversely, a low animal protein intake, such as taken by vegetarians, was associated with a low excretion of calcium, oxalate and uric acid and a low relative probability of forming stones.","title":"Should recurrent calcium oxalate stone formers become vegetarians?"},{"docid":"MED-1426","text":"BACKGROUND: To evaluate the influence of increased dietary protein intake on bacterial colonic metabolism in healthy volunteers. METHODS: Short chain fatty acids, ammonia, and volatile organic compounds in faecal samples, and phenols in the urine of five volunteers were measured after one week of basal nutrient intake and and after one week of a diet supplemented with a protein rich food (Fortimel; Nutricia, Zoetermeer, The Netherlands). Paired t tests and factor analysis were used for statistical analysis. RESULTS: Total energy and resistant carbohydrate intake remained unchanged in each study period. The percentage energy intake delivered as dietary protein, increased significantly (from 15.4% to 23.8%; p = 0.007) during supplement intake. A significant increase in faecal ammonia (p = 0.002), faecal valeric acid (p = 0.02), and urinary p-cresol (p = 0.04) was noted during supplementary protein intake. A total of 120 different volatile compounds were isolated from the faecal samples of which 10 increased significantly during dietary protein supplementation. The change in volatile pattern, especially for S containing metabolites, was clearly shown by a factor analysis model which made a distinction between the two dietary regimens for all volunteers. CONCLUSION: An increase in dietary protein leads to altered products formation by colonic metabolism, mainly reflected by an increase in faecal ammonia, faecal volatile S substances, and urinary p-cresol.","title":"Influence of dietary protein supplements on the formation of bacterial metabolites in the colon."},{"docid":"MED-5334","text":"Until recently, intact protein that is rich in tryptophan was not seen as an alternative to pharmaceutical-grade tryptophan because protein also contains large neutral amino acids (LNAAs) that compete for transport sites across the blood-brain barrier. Recent evidence indicates that when deoiled gourd seed (a rich source of tryptophan with approximately 22 mg/g protein) is combined with glucose (a carbohydrate that reduces serum levels of competing LNAAs) a clinical effect similar to that of pharmaceutical-grade tryptophan is achieved. Objective and subjective measures of anxiety in those suffering from social phobia (also known as social anxiety disorder) were employed to measure changes in anxiety in response to a stimulus as part of a double-blind, placebo-controlled, crossover study with a wash-out period of 1 week between study sessions. Subjects were randomly assigned to start with either (i) protein-source tryptophan (deoiled gourd seed) in combination with carbohydrate or (ii) carbohydrate alone. One week after the initial session, subjects returned for a follow-up session and received the opposite treatment of that received at the first session. All 7 subjects who began the study completed the 2-week protocol. Protein-source tryptophan with carbohydrate, but not carbohydrate alone, resulted in significant improvement on an objective measure of anxiety. Protein-source tryptophan combined with a high glycemic carbohydrate is a potential anxiolytic to those suffering from social phobia.","title":"Protein-source tryptophan as an efficacious treatment for social anxiety disorder: a pilot study."},{"docid":"MED-3093","text":"BACKGROUND: Dietary intake of phosphorus is derived largely from protein sources and is a critical determinant of phosphorus balance in patients with chronic kidney disease. Information about the phosphorus content of prepared foods generally is unavailable, but it is believed to contribute significantly to the phosphorus burden of patients with chronic kidney disease. DESIGN: Analysis of dietary components. SETTING: We measured the phosphorus content of 44 food products, including 30 refrigerated or frozen precooked meat, poultry, and fish items, generally national brands. OUTCOMES: Measured and reported phosphorus content of foods. MEASUREMENTS: Phosphorus by using Association of Analytical Communities official method 984.27; protein by using Association of Analytical Communities official method 990.03. RESULTS: We found that the ratio of phosphorus to protein content in these items ranged from 6.1 to 21.5 mg of phosphorus per 1 g of protein. The mean ratio in the 19 food products with a label listing phosphorus as an additive was 14.6 mg/g compared with 9.0 mg/g in the 11 items without listed phosphorus. The phosphorus content of only 1 precooked food product was available in a widely used dietary database. LIMITATIONS: Results cannot be extrapolated to other products. Manufacturers also may alter the phosphorus content of foods at any time. Protein content was not directly measured for all foods. CONCLUSION: Better reporting of phosphorus content of foods by manufacturers could result in improved dietary phosphorus control without risk of protein malnutrition.","title":"Dietary phosphorus restriction in dialysis patients: potential impact of processed meat, poultry, and fish products as protein sources."},{"docid":"MED-4353","text":"We have compared the effects of dietary soy protein and casein in diets low in cholesterol (less than 100 mg/d) and in diets enriched in cholesterol (500 mg/d) to examine whether the level of cholesterol intake affects the response of plasma lipoproteins to dietary proteins of plant and animal origin. Normal men and women consumed formula diets containing 20% of calories as soy protein or casein, 27% as fat and 53% as carbohydrate in 2 crossover studies. The dietary periods lasted for 31 days and were separated by a month-long interim period on self-chosen food. Following an initial reduction of plasma total cholesterol and low-density lipoprotein-cholesterol (LDL-C) levels on all diets, the plasma lipid and lipoprotein concentrations stabilized. On low-cholesterol diets the concentration of each of the major lipoprotein classes were similar during the soy and the casein dietary periods. On cholesterol-enriched diets, the concentration of LDL-C stabilized at a 16% lower level on soy protein than on the casein diet (p less than 0.02), while the concentration of high-density lipoprotein-cholesterol (HDL-C) was 16% higher (p less than 0.01). Since the difference in LDL-C (p less than 0.05) and in HDL-C (p less than 0.025) levels on casein and on soy protein diets were significantly greater on the high than on the low cholesterol intake, the findings indicate that the level of dietary cholesterol may determine whether plant and animal dietary proteins have similar or different effects on plasma LDL-C and HDL-C concentrations.","title":"Effects of dietary proteins on plasma lipoprotein levels in normal subjects: interaction with dietary cholesterol."},{"docid":"MED-4408","text":"The influence of protein oxidation, as measured by the dinitrophenylhydrazine (DNPH) method, on colour and texture changes during chill storage (2 degrees C, 12days) of cooked burger patties was studied. Extracts from arbutus-berries (Arbutus unedoL., AU), common hawthorns (Crataegus monogynaL., CM), dog roses (Rosa caninaL., RC) and elm-leaf blackberries (Rubus ulmifoliusSchott., RU) were prepared, added to burger patties (3% of total weight) and evaluated as inhibitors of protein oxidation and colour and texture changes. Negative (no added extract, C) and positive control (added quercetin; 230mg/kg, Q) groups were also considered. The significant increase of protein carbonyls during chill storage of control burger patties reflect the intense oxidative degradation of the muscle proteins. Concomitantly, an intense loss of redness and increase of hardness was found to take place in burger patties throughout refrigerated storage. Most fruit extracts as well as Q significantly reduced the formation of protein carbonyls and inhibited colour and texture deterioration during chill storage. Likely mechanisms through which protein oxidation could play a major role on colour and texture changes during chill storage of burger patties are discussed. Amongst the extracts, RC was most suitable for use as a functional ingredient in processed meats since it enhanced oxidative stability, colour and texture properties of burger patties with no apparent drawbacks. Copyright 2010 Elsevier Ltd. All rights reserved.","title":"Protein oxidation in emulsified cooked burger patties with added fruit extracts: Influence on colour and texture deterioration during chill storage."},{"docid":"MED-2978","text":"Diets high in protein have shown positive effects on short-term weight reduction and glycaemic control. However, the understanding of how dietary macronutrient composition relates to long-term risk of type 2 diabetes is limited. The aim of the present study was to examine intakes of macronutrients, fibre and protein sources in relation to incident type 2 diabetes. In total, 27 140 individuals, aged 45-74 years, from the population-based Malmö Diet and Cancer cohort, were included. Dietary data were collected with a modified diet history method, including registration of cooked meals. During 12 years of follow-up, 1709 incident type 2 diabetes cases were identified. High protein intake was associated with increased risk of type 2 diabetes (hazard ratio (HR) 1.27 for highest compared with lowest quintile; 95 % CI 1.08, 1.49; P for trend = 0.01). When protein consumption increased by 5 % of energy at the expense of carbohydrates (HR 1.20; 95 % CI 1.09, 1.33) or fat (HR 1.21; 95 % CI 1.09, 1.33), increased diabetes risk was observed. Intakes in the highest quintiles of processed meat (HR 1.16; 95 % CI 1.00, 1.36; P for trend = 0.01) and eggs (HR 1.21; 95 % CI 1.04, 1.41; P for trend = 0.02) were associated with increased risk. Intake of fibre-rich bread and cereals was inversely associated with type 2 diabetes (HR 0.84; 95 % CI 0.73, 0.98; P for trend = 0.004). In conclusion, results from the present large population-based prospective study indicate that high protein intake is associated with increased risk of type 2 diabetes. Replacing protein with carbohydrates may be favourable, especially if fibre-rich breads and cereals are chosen as carbohydrate sources.","title":"High intakes of protein and processed meat associate with increased incidence of type 2 diabetes."},{"docid":"MED-825","text":"BACKGROUND: Some evidence has suggested that a diet with a higher ratio of protein to carbohydrates has metabolic advantages in the treatment of polycystic ovary syndrome (PCOS). OBJECTIVE: The objective of this study was to compare the effect of a high-protein (HP) diet to a standard-protein (SP) diet in women with PCOS. DESIGN: A controlled, 6-mo trial was conducted in 57 PCOS women. The women were assigned through rank minimization to one of the following 2 diets without caloric restriction: an HP diet (>40% of energy from protein and 30% of energy from fat) or an SP diet (<15% of energy from protein and 30% of energy from fat). The women received monthly dietary counseling. At baseline and 3 and 6 mo, anthropometric measurements were performed, and blood samples were collected. RESULTS: Seven women dropped out because of pregnancy, 23 women dropped out because of other reasons, and 27 women completed the study. The HP diet produced a greater weight loss (mean: 4.4 kg; 95% CI: 0.3, 8.6 kg) and body fat loss (mean: 4.3 kg; 95% CI: 0.9, 7.6 kg) than the SP diet after 6 mo. Waist circumference was reduced more by the HP diet than by the SP diet. The HP diet produced greater decreases in glucose than did the SP diet, which persisted after adjustment for weight changes. There were no differences in testosterone, sex hormone-binding globulin, and blood lipids between the groups after 6 mo. However, adjustment for weight changes led to significantly lower testosterone concentrations in the SP-diet group than in the HP-diet group. CONCLUSION: Replacement of carbohydrates with protein in ad libitum diets improves weight loss and improves glucose metabolism by an effect that seems to be independent of the weight loss and, thus, seems to offer an improved dietary treatment of PCOS women.","title":"Effects of increased dietary protein-to-carbohydrate ratios in women with polycystic ovary syndrome."},{"docid":"MED-4612","text":"Amino acids modulate the secretion of both insulin and glucagon; the composition of dietary protein therefore has the potential to influence the balance of glucagon and insulin activity. Soy protein, as well as many other vegan proteins, are higher in non-essential amino acids than most animal-derived food proteins, and as a result should preferentially favor glucagon production. Acting on hepatocytes, glucagon promotes (and insulin inhibits) cAMP-dependent mechanisms that down-regulate lipogenic enzymes and cholesterol synthesis, while up-regulating hepatic LDL receptors and production of the IGF-I antagonist IGFBP-1. The insulin-sensitizing properties of many vegan diets--high in fiber, low in saturated fat--should amplify these effects by down-regulating insulin secretion. Additionally, the relatively low essential amino acid content of some vegan diets may decrease hepatic IGF-I synthesis. Thus, diets featuring vegan proteins can be expected to lower elevated serum lipid levels, promote weight loss, and decrease circulating IGF-I activity. The latter effect should impede cancer induction (as is seen in animal studies with soy protein), lessen neutrophil-mediated inflammatory damage, and slow growth and maturation in children. In fact, vegans tend to have low serum lipids, lean physiques, shorter stature, later puberty, and decreased risk for certain prominent 'Western' cancers; a vegan diet has documented clinical efficacy in rheumatoid arthritis. Low-fat vegan diets may be especially protective in regard to cancers linked to insulin resistance--namely, breast and colon cancer--as well as prostate cancer; conversely, the high IGF-I activity associated with heavy ingestion of animal products may be largely responsible for the epidemic of 'Western' cancers in wealthy societies. Increased phytochemical intake is also likely to contribute to the reduction of cancer risk in vegans. Regression of coronary stenoses has been documented during low-fat vegan diets coupled with exercise training; such regimens also tend to markedly improve diabetic control and lower elevated blood pressure. Risk of many other degenerative disorders may be decreased in vegans, although reduced growth factor activity may be responsible for an increased risk of hemorrhagic stroke. By altering the glucagon/insulin balance, it is conceivable that supplemental intakes of key non-essential amino acids could enable omnivores to enjoy some of the health advantages of a vegan diet. An unnecessarily high intake of essential amino acids--either in the absolute sense or relative to total dietary protein--may prove to be as grave a risk factor for 'Western' degenerative diseases as is excessive fat intake.","title":"Vegan proteins may reduce risk of cancer, obesity, and cardiovascular disease by promoting increased glucagon activity."},{"docid":"MED-2150","text":"Previous investigations, of adolescent diet recalled in adulthood, found lower risk for benign breast disease (BBD) with higher intakes of vegetable fat and nuts during high school. We investigate whether vegetable protein and fat, derived from diets reported during pre-adolescence and adolescence, are associated with subsequent risk for BBD in young women. The Growing Up Today Study includes 9,039 females, 9–15 years in 1996, who completed questionnaires annually through 2001, and then in 2003, 2005, 2007, and 2010. Food frequency questionnaires (1996–2001) obtained intake data on a variety of foods. Beginning in 2005, women (18–30 years) reported whether they had ever been diagnosed with BBD that was confirmed by breast biopsy (n = 112 cases). Logistic regression estimated associations between intakes of vegetable protein and fat and biopsy-confirmed BBD. Those individual foods that were the largest contributors of protein and fat in this cohort were also investigated. In analyses of intakes from 1996 through 1998, when our cohort was youngest, vegetable fat (OR = 0.72/(10 gm/day), 95 % CI 0.53–0.98; p = 0.04) was inversely associated with BBD risk. The greatest sources of vegetable fat and protein in these girls were peanut butter, peanuts, nuts, beans (beans, lentils, and soybeans), and corn. A daily serving of any one of these was associated with lower risk (OR = 0.32/(serv/day), 95 % CI 0.13–0.79; p = 0.01). Peanut butter (and nuts) at age 11 years was inversely associated with risk (p = 0.01). In analyses of intakes at age 14 years, vegetable protein was associated with lower BBD risk (OR = 0.64/(10 gm/day), 95 % CI 0.43–0.95; p = 0.03). A daily serving at 14 years of any one of the foods was associated with lower risk (OR = 0.34, 95 % CI 0.16–0.75; p = 0.01), as was peanut butter (and nuts) (p = 0.02). Girls with a family history of breast cancer had significantly lower risk if they consumed these foods or vegetable fat. In conclusion, consumption of vegetable protein, fat, peanut butter, or nuts by older girls may help reduce their risk of BBD as young women.","title":"Vegetable protein and vegetable fat intakes in pre-adolescent and adolescent girls, and risk for benign breast disease in young women"},{"docid":"MED-1324","text":"Six noninsulin-dependent diabetic subjects received meals containing 25 g carbohydrate either as potato or as spaghetti. The meals were repeated with the addition of 25 g protein and with 25 g protein and 25 g fat. Blood glucose and insulin responses were measured for 4 h after the test meal. When carbohydrate was given alone, the blood glucose and serum insulin increments were higher for the potato meal. The addition of protein increased the insulin responses to both carbohydrates and slightly reduced the glycemic response to mashed potato (F = 2.04, p less than 0.05). The further addition of fat reduced the glycemic response to mashed potato (F = 14.63, p less than 0.001) without any change in the blood glucose response to spaghetti (F = 0.94, NS). The different responses to coingestion of protein and fat reduced the difference between the glycemic responses to the two carbohydrates.","title":"Differential effect of protein and fat ingestion on blood glucose responses to high- and low-glycemic-index carbohydrates in noninsulin-dependent d..."},{"docid":"MED-1134","text":"BACKGROUND: The purpose of this article is to evaluate the impact of low protein and high fiber intakes on risk factors of stone recurrence in idiopathic calcium stone formers (ICSFs). METHODS: Ninety-six ICSFs were randomly assigned a low animal protein diet (< 10% of total energy), a high-fiber diet (> 25 g/day), or a usual diet (control group); all patients were recommended to increase their fluid intake. Their daily urine compositions were analyzed at baseline and at four months. Compliance with dietary recommendations was checked by validated food frequency questionnaires. Compliance with total and animal protein intakes was assessed by 24-hour urea and sulfate outputs, respectively. The nutritional intervention (oral instructions, written leaflet, phoning) and food assessment were carried out by a research dietitian. RESULTS: At baseline, diets and the daily urine composition did not differ between the three groups. At four months, while diets differed significantly, the 24-hour output of calcium and oxalate did not differ significantly within and between groups after adjustment for potential confounders (age, sex, and personal and family history of calcium stones) and baseline values. However, as many as 12 out of 31 ICSFs (95% CI, 22 to 58%) assigned to a low animal protein diet achieved a reduction in the urine urea excretion rate of more than 50 mmol/day and also exhibited a significant decrease in urinary calcium excretion that averaged 1.8 mmol/day. A significant correlation between urea and calcium outputs was observed only among patients with hypercalciuria. CONCLUSIONS: These results show that only ICSFs who markedly decrease their animal protein intake, especially those with hypercalciuria, can expect to benefit from dietary recommendations.","title":"Effects of low animal protein or high-fiber diets on urine composition in calcium nephrolithiasis."},{"docid":"MED-4342","text":"OBJECTIVES: Diet composition has long been suspected to contribute to inflammatory bowel disease (IBD), but has not been thoroughly assessed, and has been assessed only in retrospective studies that are prone to recall bias. The aim of the present study was to evaluate the role of dietary macronutrients in the etiology of IBD in a large prospective cohort. METHODS: The Etude Épidémiologique des femmes de la Mutuelle Générale de l'Education Nationale cohort consists of women living in France, aged 40-65 years, and free of major diseases at inclusion. A self-administered questionnaire was used to record dietary habits at baseline. Questionnaires on disease occurrence and lifestyle factors were completed every 24 months. IBDs were assessed in each questionnaire until June 2005, and subsequently validated using clinical and pathological criteria. We estimated the association between nutrients or foods and IBD using Cox proportional hazards models adjusted for energy intake. RESULTS: Among 67,581 participants (705,445 person-years, mean follow-up since completion of the baseline dietary questionnaire 10.4 years), we validated 77 incident IBD cases. High total protein intake, specifically animal protein, was associated with a significantly increased risk of IBD, (hazards ratio for the third vs. first tertile and 95% confidence interval being 3.31 and 1.41-7.77 (P trend=0.007), and 3.03 and 1.45-6.34 (P trend=0.005) for total and animal protein, respectively). Among sources of animal protein, high consumption of meat or fish but not of eggs or dairy products was associated with IBD risk. CONCLUSIONS: High protein intake is associated with an increased risk of incident IBD in French middle-aged women.","title":"Animal protein intake and risk of inflammatory bowel disease: The E3N prospective study."},{"docid":"MED-4352","text":"Changes in the concentration and composition of serum VLDL, LDL, and HDL were studied in rabbits transferred from Chow diets to cholesterol-free, semipurified diets containing casein or isolated soy protein. During the first week on the casein diet, there was a marked increase in LDL-cholesterol and these higher levels were maintained during the subsequent 3 weeks of the study. Similar but less marked changes were obtained with the soy protein diet. When the percent composition of the particles was determined, both VLDL and LDL had a higher proportion of cholesterol. Turnover studies indicated that the FCRs for radiolabelled VLDL and LDL were reduced in casein-fed animals compared to those fed soy protein. The elevated LDL levels in casein-fed rabbits were primarily due to a reduction in receptor-mediated catabolism of LDL-apo B. Receptor-independent removal in the two groups was similar. These studies show that the hypercholesterolemia in casein-fed rabbits, compared to those fed soy protein, is associated with cholesterol enrichment of LDL and impaired receptor-dependent removal of LDL-apo B.","title":"Effects of dietary protein on composition and metabolism of plasma lipoproteins in rabbits."},{"docid":"MED-4898","text":"We examined consumption of animal foods, protein and calcium in relation to risk of prostate cancer among 142 251 men in the European Prospective Investigation into Cancer and Nutrition. Associations were examined using Cox regression, stratified by recruitment centre and adjusted for height, weight, education, marital status and energy intake. After an average of 8.7 years of follow-up, there were 2727 incident cases of prostate cancer, of which 1131 were known to be localised and 541 advanced-stage disease. A high intake of dairy protein was associated with an increased risk, with a hazard ratio for the top versus the bottom fifth of intake of 1.22 (95% confidence interval (CI): 1.07–1.41, Ptrend=0.02). After calibration to allow for measurement error, we estimated that a 35-g day−1 increase in consumption of dairy protein was associated with an increase in the risk of prostate cancer of 32% (95% CI: 1–72%, Ptrend=0.04). Calcium from dairy products was also positively associated with risk, but not calcium from other foods. The results support the hypothesis that a high intake of protein or calcium from dairy products may increase the risk for prostate cancer.","title":"Animal foods, protein, calcium and prostate cancer risk: the European Prospective Investigation into Cancer and Nutrition"},{"docid":"MED-1440","text":"Aging and metabolism-related disorders are risk factors for Alzheimer disease (AD). Since sirtuins may increase the lifespan through regulation of cellular metabolism, we compared the concentration of sirtuin 1 (SIRT1) in the brains of AD patients (n = 19) and controls (n = 22) using Western immunoblots and in situ hybridization. We report a significant reduction of SIRT1 (mRNA: −29%; protein: −45%) in the parietal cortex of AD patients, but not in the cerebellum. Further analyses in a second cohort of 36 subjects confirmed that cortical SIRT1 was decreased in the cortex of AD patients but not in individuals with mild cognitive impairment. SIRT1 mRNA and its translated protein correlated negatively with the duration of symptoms (mRNA: r2 = −0.367; protein: r2 = −0.326) and the accumulation of paired helical filament tau (mRNA: r2 = −0.230; protein: r2 = −0.119), but weakly with insoluble amyloid-β(Aβ42 (mRNA: r2 = −0.090; protein: r2 = −0.072). A significant relationship between SIRT1 levels and global cognition scores proximate to death was also found (r2 = +0.09; p = 0.049). In contrast, cortical SIRT1 levels remained unchanged in a triple-transgenic animal model of AD. Collectively, our results indicate that loss of SIRT1 is closely associated with the accumulation of Aβ and tau in the cerebral cortex of patients with AD.","title":"SIRT1 Decrease Parallels the Accumulation of tau in Alzheimer Disease"},{"docid":"MED-2315","text":"Background The word selectivity describes a drug's ability to affect a particular cell population in preference to others. As part of the current state of art in the search for new therapeutic agents, the property of selectivity is a mode of action thought to have a high degree of desirability. Consequently there is a growing activity in this area of research. Selectivity is generally a worthy property in a drug because a drug having high selectivity may have a dramatic effect when there is a single agent that can be targeted against the appropriate molecular-driver involved in the pathogenesis of a disease. An example is chronic myeloid leukemia (CML). CML has a specific chromosomal abnormality, the Philadelphia chromosome, that results in a single gene that produces an abnormal protein Discussion There is a burgeoning understanding of the cellular mechanisms that control the etiology and pathogeneses of diseases. This understanding both enables and motivates the development of drugs that induce a specific action in a selected cell population; i.e., a targeted treatment. Consequently, drugs that can target distinct molecular targets involved in pathologic/pathogenetic processes, or signal-transduction pathways, are being developed. However, in most cases, diseases involve multiple abnormalities. A disease may be associated with more than one dysfunctional protein and these may be out-of-balance with each other. Likewise a drug might strongly target a protein that shares a similar active domain with other proteins. A drug may also target pleiotropic cytokines, or other proteins that have multi-physiological functions. In this way multiple normal cellular pathways can be simultaneously influenced. Long term experience with drugs supposedly designed for only a single target, but which unavoidably involve other functional effects, is uncovering the fact that molecular targeting is not medically flawless. Summary We contend that an ideal drug may be one whose efficacy is based not on the inhibition of a single target, but rather on the rebalancing of the several proteins or events, that contribute to the etiology, pathogeneses, and progression of diseases, i.e., in effect a promiscuous drug. Ideally, if this could be done at minimum drug concentration, side effects could be minimized. Corollaries to this argument are that the growing fervor for researching truly selective drugs may be imprudent when considering the totality of responses; and that the expensive screening techniques used to discover these, may be both medically and financially inefficient.","title":"Promiscuous drugs compared to selective drugs (promiscuity can be a virtue)"},{"docid":"MED-2603","text":"FAS-associated protein with death domain (FADD) is the key adaptor protein transmitting apoptotic signals mediated by the main death receptors (DRs). Besides being an essential instrument in cell death, FADD is also implicated in proliferation, cell cycle progression, tumor development, inflammation, innate immunity, and autophagy. Recently, many of these new functions of FADD were shown to be independent of DRs. Moreover, FADD function is dictated by protein localization and phosphorylation state. Thus, FADD is a crucial and unique controller of many essential cellular processes. The full understanding of the networks dictating the ultimate function of FADD may provide a new paradigm for other multifaceted proteins. Copyright 2010 Elsevier Ltd. All rights reserved.","title":"FADD: a regulator of life and death."},{"docid":"MED-2136","text":"Prostate cancer (PCa) is dependent on androgen receptor signaling and aberrations of the PI3K-Akt-mTORC1 pathway mediating excessive and sustained growth signaling. The nutrient-sensitive kinase mTORC1 is upregulated in nearly 100% of advanced human PCas. Oncogenic mTORC1 signaling activates key subsets of mRNAs that cooperate in distinct steps of PCa initiation and progression. Epidemiological evidence points to increased dairy protein consumption as a major dietary risk factor for the development of PCa. mTORC1 is a master regulator of protein synthesis, lipid synthesis and autophagy pathways that couple nutrient sensing to cell growth and cancer. This review provides evidence that PCa initiation and progression are promoted by cow´s milk, but not human milk, stimulation of mTORC1 signaling. Mammalian milk is presented as an endocrine signaling system, which activates mTORC1, promotes cell growth and proliferation and suppresses autophagy. Naturally, milk-mediated mTORC1 signaling is restricted only to the postnatal growth phase of mammals. However, persistent consumption of cow´s milk proteins in humans provide highly insulinotropic branched-chain amino acids (BCAAs) provided by milk´s fast hydrolysable whey proteins, which elevate postprandial plasma insulin levels, and increase hepatic IGF-1 plasma concentrations by casein-derived amino acids. BCAAs, insulin and IGF-1 are pivotal activating signals of mTORC1. Increased cow´s milk protein-mediated mTORC1 signaling along with constant exposure to commercial cow´s milk estrogens derived from pregnant cows may explain the observed association between high dairy consumption and increased risk of PCa in Westernized societies. As well-balanced mTORC1-signaling plays an important role in appropriate prostate morphogenesis and differentiation, exaggerated mTORC1-signaling by high cow´s milk consumption predominantly during critical growth phases of prostate development and differentiation may exert long-term adverse effects on prostate health. Attenuation of mTORC1 signaling by contemporary Paleolithic diets and restriction of dairy protein intake, especially during mTORC1-dependent phases of prostate development and differentiation, may offer protection from the most common dairy-promoted cancer in men of Western societies.","title":"The impact of cow's milk-mediated mTORC1-signaling in the initiation and progression of prostate cancer"},{"docid":"MED-4852","text":"OBJECTIVES: A dietary link to rheumatoid arthritis (RA) has been suspected and an influence on arthritic symptoms by different diets has been reported. Our primary aim was to record the self-experienced adverse food reactions in patients with RA. A secondary aim was to relate self-experienced adverse reactions to dairy produce and wheat to the local mucosal reactivity observed after rectal challenge with cow's milk protein (CM) and wheat gluten. METHODS: A questionnaire about self-experienced adverse reaction to food was sent to 347 RA patients. Rectal challenge with CM and gluten was performed in 27 of these patients and in healthy controls (n = 18). After a 15-h challenge the mucosal production of nitric oxide (NO) and the mucosal release of myeloperoxidase (MPO) and eosinophil cationic protein (ECP) were measured by using the mucosal patch technique. RESULTS: Twenty-seven per cent of the RA patients reported food intolerance (FI) to various foods, and in particular to CM, meat, and wheat gluten. Strong mucosal reactivity to CM was observed in 11% of the patients. Moderately increased mucosal reactivity to CM and gluten was found in 22% and 33%, respectively, of the patients. No relationship was found between self-experienced adverse reactions to CM or gluten and mucosal reactivity to these proteins. CONCLUSIONS: Perceived FI is reported frequently by RA patients, with a prevalence similar to that reported previously in the general population. Mucosal reactivity to CM and gluten is seen in a minor fraction of RA patients and is not related to the frequently perceived intolerance to these proteins.","title":"Self-reported food intolerance and mucosal reactivity after rectal food protein challenge in patients with rheumatoid arthritis."}],"string":"[\n {\n \"docid\": \"MED-1807\",\n \"text\": \"BACKGROUND: As protein is considered to increase thermogenesis and satiety more than other macronutrients, it may have beneficial effects on prevention of weight gain and weight maintenance. OBJECTIVE: The objective of this study is to assess the association between the amount and type of dietary protein, and subsequent changes in weight and waist circumference (WC). METHODS: 89,432 men and women from five countries participating in European Prospective Investigation into Cancer and Nutrition (EPIC) were followed for a mean of 6.5 years. Associations between the intake of protein or subgroups of protein (from animal and plant sources) and changes in weight (g per year) or WC (cm per year) were investigated using gender and centre-specific multiple regression analyses. Adjustments were made for other baseline dietary factors, baseline anthropometrics, demographic and lifestyle factors and follow-up time. We used random effect meta-analyses to obtain pooled estimates across centres. RESULTS: Higher intake of total protein, and protein from animal sources was associated with subsequent weight gain for both genders, strongest among women, and the association was mainly attributable to protein from red and processed meat and poultry rather than from fish and dairy sources. There was no overall association between intake of plant protein and subsequent changes in weight. No clear overall associations between intakes of total protein or any of the subgroups and changes in WC were present. The associations showed some heterogeneity between centres, but pooling of estimates was still considered justified. CONCLUSION: A high intake of protein was not found associated with lower weight or waist gain in this observational study. In contrast, protein from food items of animal origin, especially meat and poultry, seemed to be positively associated with long-term weight gain. There were no clear associations for waist changes.\",\n \"title\": \"Intake of total, animal and plant protein and subsequent changes in weight or waist circumference in European men and women: the Diogenes project.\"\n },\n {\n \"docid\": \"MED-1446\",\n \"text\": \"Literature on the association of protein intake with body weight is inconsistent. Little is known about the relation of long-term protein intake to obesity. This study aimed to determine the association between protein intake and obesity. A cohort of 1,730 employed white men ages 40–55 years from the Chicago Western Electric Study was followed from 1958 to 1966. Diet was assessed twice with Burke’s comprehensive diet history method, at two baseline examinations; height, weight, and other covariates were measured annually by trained interviewers. Generalized estimating equation (GEE) was used to examine the relation of baseline total, animal, and vegetable protein intake to likelihood of being overweight or obese at sequential annual examinations. Dietary animal protein was positively related to overweight and obesity over seven years of follow up. With adjustment for potential confounders (age, education, cigarette smoking, alcohol intake, energy, carbohydrate and saturated fat intake, and history of diabetes or other chronic disease), the odds ratios (95% confidence intervals) for obesity were 4.62 (2.68–7.98, p for trend<0.01) for participants in the highest compared to the lowest quartile of animal protein and 0.58 (0.36, 0.95, p for trend=0.053) for those in the highest quartile of vegetable protein intake. A statistically significant, positive association was seen between animal protein intake and obesity; those in higher quartiles of vegetable protein intake had lower odds of being obese. These results indicate that animal and vegetable protein may relate differently to occurrence of obesity in the long run.\",\n \"title\": \"Longitudinal association between animal and vegetable protein intake and obesity among adult males in the United States: the Chicago Western Electric Study\"\n },\n {\n \"docid\": \"MED-1869\",\n \"text\": \"Observational and clinical studies suggest that high protein intake, particularly protein from plant sources, might reduce blood pressure (BP). To examine the association of dietary protein with BP, we analysed data from PREMIER, an 18-month clinical trial (n=810) that examined the effects of two multi-component lifestyle modifications on BP. We examined the association of protein intake with BP, and in particular the independent relationship of plant and animal protein with BP. Multivariable linear regression analyses were performed with both cross-sectional and longitudinal data. Dietary plant protein was inversely associated with both systolic and diastolic BP in cross-sectional analyses at the 6-month follow-up (P=0.0045 and 0.0096, respectively). Fruit and vegetable intake was also inversely associated with both systolic and diastolic BP cross-sectionally at 6 months (P=0.0003 and 0.0157, respectively). In longitudinal analyses, a high intake of plant protein at 6 months was marginally associated with a reduction of both systolic and diastolic BP from baseline to 6 months only (P=0.0797 and 0.0866, respectively), independent of change in body weight and waist circumference. Furthermore, increased intake of plant protein, and fruits and vegetables was significantly associated with a lower risk of hypertension at 6 but not at 18 months. Results of this study indicate that plant protein had a beneficial effect on BP and was associated with a lower risk of hypertension at 6 months. Our data, in conjunction with other research, suggest that an increased intake of plant protein may be useful as a means to prevent and treat hypertension.\",\n \"title\": \"The relationship between dietary protein intake and blood pressure: results from the PREMIER study.\"\n },\n {\n \"docid\": \"MED-1281\",\n \"text\": \"The calcium ion (Ca2+) is a ubiquitous second messenger that is crucial for the regulation of a wide variety of cellular processes. The diverse transient signals transduced by Ca2+ are mediated by intracellular Ca2+-binding proteins, also known as Ca2+ sensors. A key obstacle to studying many Ca2+-sensing proteins is the difficulty in identifying the numerous downstream target interactions that respond to Ca2+-induced conformational changes. Among a number of Ca2+ sensors in the eukaryotic cell, calmodulin (CaM) is the most widespread and the best studied. Employing the mRNA display technique, we have scanned the human proteome for CaM-binding proteins and have identified and characterized a large number of both known and previously uncharacterized proteins that interact with CaM in a Ca2+-dependent manner. The interactions of several identified proteins with Ca2+/CaM were confirmed by using pull-down assays and coimmunoprecipitation. Many of the CaM-binding proteins identified belong to protein families such as the DEAD/H box proteins, ribosomal proteins, proteasome 26S subunits, and deubiquitinating enzymes, suggesting the possible involvement of Ca2+/CaM in different signaling pathways. The selection method described herein could be used to identify the binding partners of other calcium sensors on the proteome-wide scale.\",\n \"title\": \"Scanning the human proteome for calmodulin-binding proteins\"\n },\n {\n \"docid\": \"MED-5199\",\n \"text\": \"Studies attempting to evaluate protein assimilation in humans have hitherto relied on either ileostomy subjects or intubation techniques. The availability of stable isotope-labeled protein allowed us to determine the amount and fate of dietary protein escaping digestion and absorption in the small intestine of healthy volunteers using noninvasive tracer techniques. Ten healthy volunteers were studied once after ingestion of a cooked test meal, consisting of 25 g of (13)C-, (15)N-, and (2)H-labeled egg protein, and once after ingestion of the same but raw meal. Amounts of 5.73% and 35.10% (P < 0.005) of cooked and raw test meal, respectively, escaped digestion and absorption in the small intestine. A significantly higher percentage of the malabsorbed raw egg protein was recovered in urine as fermentation metabolites. These results 1) confirm that substantial amounts of even easily digestible proteins may escape assimilation in healthy volunteers and 2) further support the hypothesis that the metabolic fate of protein in the colon is affected by the amount of protein made available.\",\n \"title\": \"Amount and fate of egg protein escaping assimilation in the small intestine of humans.\"\n },\n {\n \"docid\": \"MED-1425\",\n \"text\": \"We examined the correlation between the incidence of Crohn disease and dietary change in a relatively homogeneous Japanese population. The incidence and daily intake of each dietary component were compared annually from 1966 to 1985. The univariate analysis showed that the increased incidence of Crohn disease was strongly (P < 0.001) correlated with increased dietary intake of total fat (r = 0.919). animal fat (r = 0.880), n-6 polyunsaturated fatty acids (r = 0.883), animal protein (r = 0.908), milk protein (r = 0.924), and the ratio of n-6 to n-3 fatty acid intake (r = 0.792). It was less correlated with intake of total protein (r = 0.482, P < 0.05), was not correlated with intake of fish protein (r = 0.055, P > 0.1), and was inversely correlated with intake of vegetable protein (r = -0.941, P < 0.001). The multivariate analysis showed that increased intake of animal protein was the strongest independent factor with a weaker second factor, an increased ration of n-6 to n-3 polyunsaturated fatty acids. The present study in association with reported clinical studies suggests that increased dietary intake of animal protein and n-6 polyunsaturated fatty acids with less n-3 polyunsaturated fatty acids may contribute to the development of Crohn disease.\",\n \"title\": \"Epidemiologic analysis of Crohn disease in Japan: increased dietary intake of n-6 polyunsaturated fatty acids and animal protein relates to the inc...\"\n },\n {\n \"docid\": \"MED-2943\",\n \"text\": \"BACKGROUND: Western diets, which typically contain large amounts of energy-dense processed foods, together with a sedentary lifestyle are associated with increased cardiometabolic risk. We evaluated the long-term effects of consuming a low-calorie low-protein vegan diet or performing regular endurance exercise on cardiometabolic risk factors. METHODS: In this cross-sectional study, cardiometabolic risk factors were evaluated in 21 sedentary subjects, who had been on a low-calorie low-protein raw vegan diet for 4.4 +/- 2.8 years, (mean age, 53.1 +/- 11 yrs), 21 body mass index (BMI)-matched endurance runners consuming Western diets, and 21 age- and gender-matched sedentary subjects, consuming Western diets. RESULTS: BMI was lower in the low-calorie low-protein vegan diet (21.3 +/- 3.1 kg/m(2)) and endurance runner (21.1 +/- 1.6 kg/m(2)) groups than in the sedentary Western diet group (26.5 +/- 2.7 kg/m(2)) (p < 0.005). Plasma concentrations of lipids, lipoproteins, glucose, insulin, C-reactive protein, blood pressure (BP), and carotid artery intima-media thickness were lower in the low-calorie low-protein vegan diet and runner groups than in the Western diet group (all p < 0.05). Both systolic and diastolic BP were lower in the low-calorie low-protein vegan diet group (104 +/- 15 and 62 +/- 11 mm Hg) than in BMI-matched endurance runners (122 +/- 13 and 72 +/- 9 mmHg) and Western diet group (132 +/- 14 and 79 +/- 8 mm Hg) (p < 0.001); BP values were directly associated with sodium intake and inversely associated with potassium and fiber intake. CONCLUSIONS: Long-term consumption of a low-calorie low-protein vegan diet or regular endurance exercise training is associated with low cardiometabolic risk. Moreover, our data suggest that specific components of a low-calorie low-protein vegan diet provide additional beneficial effects on blood pressure.\",\n \"title\": \"Long-term low-calorie low-protein vegan diet and endurance exercise are associated with low cardiometabolic risk.\"\n },\n {\n \"docid\": \"MED-4509\",\n \"text\": \"Hypercholesterolemia is a major modifiable risk factor for cardiovascular disease. Some, but not all, studies have shown that soy protein intake decreases total and low-density lipoprotein cholesterol and triglycerides and increases high-density lipoprotein cholesterol. The objective of this meta-analysis was to examine the effect of soy protein supplementation on serum lipid levels in adults. English language articles were retrieved by searching MEDLINE (1966 to February 2005) and the bibliographies of the retrieved articles. A total of 41 randomized controlled trials in which isolated soy protein supplementation was the only intervention and the net changes in serum lipids during intervention were reported. Information on study design, sample size, participant characteristics, intervention, follow-up duration, and treatment outcomes was independently abstracted using a standardized protocol. Using a random-effects model, data from each study were pooled and weighted by the inverse of their variance. Soy protein supplementation was associated with a significant reduction in mean serum total cholesterol (-5.26 mg/dl, 95% confidence interval [CI] -7.14 to -3.38), low-density lipoprotein cholesterol (-4.25 mg/dl, 95% CI -6.00 to -2.50), and triglycerides (-6.26 mg/dl, 95% CI -9.14 to -3.38) and a significant increase in high-density lipoprotein cholesterol (0.77 mg/dl, 95% CI 0.20 to 1.34). Meta-regression analyses showed a dose-response relation between soy protein and isoflavone supplementation and net changes in serum lipids. These results indicate that soy protein supplementation reduces serum lipids among adults with or without hypercholesterolemia. In conclusion, replacing foods high in saturated fat, trans-saturated fat, and cholesterol with soy protein may have a beneficial effect on coronary risk factors.\",\n \"title\": \"A meta-analysis of the effect of soy protein supplementation on serum lipids.\"\n },\n {\n \"docid\": \"MED-1323\",\n \"text\": \"Background: Fat and protein sources may influence whether low-carbohydrate diets are associated with type 2 diabetes (T2D). Objective: The objective was to compare the associations of 3 low-carbohydrate diet scores with incident T2D. Design: A prospective cohort study was conducted in participants from the Health Professionals Follow-Up Study who were free of T2D, cardiovascular disease, or cancer at baseline (n = 40,475) for up to 20 y. Cumulative averages of 3 low-carbohydrate diet scores (high total protein and fat, high animal protein and fat, and high vegetable protein and fat) were calculated every 4 y from food-frequency questionnaires and were associated with incident T2D by using Cox models. Results: We documented 2689 cases of T2D during follow-up. After adjustments for age, smoking, physical activity, coffee intake, alcohol intake, family history of T2D, total energy intake, and body mass index, the score for high animal protein and fat was associated with an increased risk of T2D [top compared with bottom quintile; hazard ratio (HR): 1.37; 95% CI: 1.20, 1.58; P for trend < 0.01]. Adjustment for red and processed meat attenuated this association (HR: 1.11; 95% CI: 0.95, 1.30; P for trend = 0.20). A high score for vegetable protein and fat was not significantly associated with the risk of T2D overall but was inversely associated with T2D in men aged <65 y (HR: 0.78; 95% CI: 0.66, 0.92; P for trend = 0.01, P for interaction = 0.01). Conclusions: A score representing a low-carbohydrate diet high in animal protein and fat was positively associated with the risk of T2D in men. Low-carbohydrate diets should obtain protein and fat from foods other than red and processed meat.\",\n \"title\": \"Low-carbohydrate diet scores and risk of type 2 diabetes in men\"\n },\n {\n \"docid\": \"MED-4745\",\n \"text\": \"Early puberty onset is associated with hormone-related cancers, but whether diet in childhood influences pubertal timing is controversial. We examined the association of protein intake in early and mid-childhood with the ages at take-off of the pubertal growth spurt (ATO), peak height velocity (APHV), and menarche in girls and voice break in boys using data from the longitudinal Dortmund Nutritional and Anthropometric Longitudinally Designed Study. Among participants who provided 3-d weighed dietary records at 12 mo, 18-24 mo, 3-4 y, and 5-6 y, 112 had sufficient anthropometric measurements between 6 and 13 y to allow estimation of ATO. Life-course plots were used to identify critical periods of total, animal, and vegetable protein intake (percentage of total energy intake) for pubertal timing. At these ages, the association between tertiles of protein intake (T1-T3) and the outcomes was investigated using multiple linear regression analysis. A higher total and animal protein intake at 5-6 y was related to an earlier ATO. In the highest tertile of animal protein intake at 5-6 y, ATO occurred 0.6 y earlier than in the lowest [(mean, 95% CI) T1: 9.6, 9.4-9.9 vs. T2: 9.4, 9.1-9.7 vs. T3: 9.0, 8.7-9.3 y; P-trend = 0.003, adjusted for sex, total energy, breast-feeding, birth year, and paternal university degree]. Similar findings were seen for APHV (P-trend = 0.001) and the timing of menarche/voice break (P-trend = 0.02). Conversely, a higher vegetable protein intake at 3-4 and 5-6 y was related to later ATO, APHV, and menarche/voice break (P-trend = 0.02-0.04). These results suggest that animal and vegetable protein intake in mid-childhood might be differentially related to pubertal timing.\",\n \"title\": \"Dietary protein intake throughout childhood is associated with the timing of puberty.\"\n },\n {\n \"docid\": \"MED-1135\",\n \"text\": \"The hypothesis that the incidence of calcium stone disease is related to the consumption of animal protein has been examined. Within the male population, recurrent idiopathic stone formers consumed more animal protein than did normal subjects. Single stone formers had animal protein intakes intermediate between those of normal men and those of recurrent stone formers. A high animal protein intake caused a significant increase in the urinary excretion of calcium, oxalate and uric acid, 3 of the 6 main urinary risk factors for calcium stone formation. The overall relative probability of forming stones, calculated from the combination of the 6 main urinary risk factors, was markedly increased by a high animal protein diet. Conversely, a low animal protein intake, such as taken by vegetarians, was associated with a low excretion of calcium, oxalate and uric acid and a low relative probability of forming stones.\",\n \"title\": \"Should recurrent calcium oxalate stone formers become vegetarians?\"\n },\n {\n \"docid\": \"MED-1426\",\n \"text\": \"BACKGROUND: To evaluate the influence of increased dietary protein intake on bacterial colonic metabolism in healthy volunteers. METHODS: Short chain fatty acids, ammonia, and volatile organic compounds in faecal samples, and phenols in the urine of five volunteers were measured after one week of basal nutrient intake and and after one week of a diet supplemented with a protein rich food (Fortimel; Nutricia, Zoetermeer, The Netherlands). Paired t tests and factor analysis were used for statistical analysis. RESULTS: Total energy and resistant carbohydrate intake remained unchanged in each study period. The percentage energy intake delivered as dietary protein, increased significantly (from 15.4% to 23.8%; p = 0.007) during supplement intake. A significant increase in faecal ammonia (p = 0.002), faecal valeric acid (p = 0.02), and urinary p-cresol (p = 0.04) was noted during supplementary protein intake. A total of 120 different volatile compounds were isolated from the faecal samples of which 10 increased significantly during dietary protein supplementation. The change in volatile pattern, especially for S containing metabolites, was clearly shown by a factor analysis model which made a distinction between the two dietary regimens for all volunteers. CONCLUSION: An increase in dietary protein leads to altered products formation by colonic metabolism, mainly reflected by an increase in faecal ammonia, faecal volatile S substances, and urinary p-cresol.\",\n \"title\": \"Influence of dietary protein supplements on the formation of bacterial metabolites in the colon.\"\n },\n {\n \"docid\": \"MED-5334\",\n \"text\": \"Until recently, intact protein that is rich in tryptophan was not seen as an alternative to pharmaceutical-grade tryptophan because protein also contains large neutral amino acids (LNAAs) that compete for transport sites across the blood-brain barrier. Recent evidence indicates that when deoiled gourd seed (a rich source of tryptophan with approximately 22 mg/g protein) is combined with glucose (a carbohydrate that reduces serum levels of competing LNAAs) a clinical effect similar to that of pharmaceutical-grade tryptophan is achieved. Objective and subjective measures of anxiety in those suffering from social phobia (also known as social anxiety disorder) were employed to measure changes in anxiety in response to a stimulus as part of a double-blind, placebo-controlled, crossover study with a wash-out period of 1 week between study sessions. Subjects were randomly assigned to start with either (i) protein-source tryptophan (deoiled gourd seed) in combination with carbohydrate or (ii) carbohydrate alone. One week after the initial session, subjects returned for a follow-up session and received the opposite treatment of that received at the first session. All 7 subjects who began the study completed the 2-week protocol. Protein-source tryptophan with carbohydrate, but not carbohydrate alone, resulted in significant improvement on an objective measure of anxiety. Protein-source tryptophan combined with a high glycemic carbohydrate is a potential anxiolytic to those suffering from social phobia.\",\n \"title\": \"Protein-source tryptophan as an efficacious treatment for social anxiety disorder: a pilot study.\"\n },\n {\n \"docid\": \"MED-3093\",\n \"text\": \"BACKGROUND: Dietary intake of phosphorus is derived largely from protein sources and is a critical determinant of phosphorus balance in patients with chronic kidney disease. Information about the phosphorus content of prepared foods generally is unavailable, but it is believed to contribute significantly to the phosphorus burden of patients with chronic kidney disease. DESIGN: Analysis of dietary components. SETTING: We measured the phosphorus content of 44 food products, including 30 refrigerated or frozen precooked meat, poultry, and fish items, generally national brands. OUTCOMES: Measured and reported phosphorus content of foods. MEASUREMENTS: Phosphorus by using Association of Analytical Communities official method 984.27; protein by using Association of Analytical Communities official method 990.03. RESULTS: We found that the ratio of phosphorus to protein content in these items ranged from 6.1 to 21.5 mg of phosphorus per 1 g of protein. The mean ratio in the 19 food products with a label listing phosphorus as an additive was 14.6 mg/g compared with 9.0 mg/g in the 11 items without listed phosphorus. The phosphorus content of only 1 precooked food product was available in a widely used dietary database. LIMITATIONS: Results cannot be extrapolated to other products. Manufacturers also may alter the phosphorus content of foods at any time. Protein content was not directly measured for all foods. CONCLUSION: Better reporting of phosphorus content of foods by manufacturers could result in improved dietary phosphorus control without risk of protein malnutrition.\",\n \"title\": \"Dietary phosphorus restriction in dialysis patients: potential impact of processed meat, poultry, and fish products as protein sources.\"\n },\n {\n \"docid\": \"MED-4353\",\n \"text\": \"We have compared the effects of dietary soy protein and casein in diets low in cholesterol (less than 100 mg/d) and in diets enriched in cholesterol (500 mg/d) to examine whether the level of cholesterol intake affects the response of plasma lipoproteins to dietary proteins of plant and animal origin. Normal men and women consumed formula diets containing 20% of calories as soy protein or casein, 27% as fat and 53% as carbohydrate in 2 crossover studies. The dietary periods lasted for 31 days and were separated by a month-long interim period on self-chosen food. Following an initial reduction of plasma total cholesterol and low-density lipoprotein-cholesterol (LDL-C) levels on all diets, the plasma lipid and lipoprotein concentrations stabilized. On low-cholesterol diets the concentration of each of the major lipoprotein classes were similar during the soy and the casein dietary periods. On cholesterol-enriched diets, the concentration of LDL-C stabilized at a 16% lower level on soy protein than on the casein diet (p less than 0.02), while the concentration of high-density lipoprotein-cholesterol (HDL-C) was 16% higher (p less than 0.01). Since the difference in LDL-C (p less than 0.05) and in HDL-C (p less than 0.025) levels on casein and on soy protein diets were significantly greater on the high than on the low cholesterol intake, the findings indicate that the level of dietary cholesterol may determine whether plant and animal dietary proteins have similar or different effects on plasma LDL-C and HDL-C concentrations.\",\n \"title\": \"Effects of dietary proteins on plasma lipoprotein levels in normal subjects: interaction with dietary cholesterol.\"\n },\n {\n \"docid\": \"MED-4408\",\n \"text\": \"The influence of protein oxidation, as measured by the dinitrophenylhydrazine (DNPH) method, on colour and texture changes during chill storage (2 degrees C, 12days) of cooked burger patties was studied. Extracts from arbutus-berries (Arbutus unedoL., AU), common hawthorns (Crataegus monogynaL., CM), dog roses (Rosa caninaL., RC) and elm-leaf blackberries (Rubus ulmifoliusSchott., RU) were prepared, added to burger patties (3% of total weight) and evaluated as inhibitors of protein oxidation and colour and texture changes. Negative (no added extract, C) and positive control (added quercetin; 230mg/kg, Q) groups were also considered. The significant increase of protein carbonyls during chill storage of control burger patties reflect the intense oxidative degradation of the muscle proteins. Concomitantly, an intense loss of redness and increase of hardness was found to take place in burger patties throughout refrigerated storage. Most fruit extracts as well as Q significantly reduced the formation of protein carbonyls and inhibited colour and texture deterioration during chill storage. Likely mechanisms through which protein oxidation could play a major role on colour and texture changes during chill storage of burger patties are discussed. Amongst the extracts, RC was most suitable for use as a functional ingredient in processed meats since it enhanced oxidative stability, colour and texture properties of burger patties with no apparent drawbacks. Copyright 2010 Elsevier Ltd. All rights reserved.\",\n \"title\": \"Protein oxidation in emulsified cooked burger patties with added fruit extracts: Influence on colour and texture deterioration during chill storage.\"\n },\n {\n \"docid\": \"MED-2978\",\n \"text\": \"Diets high in protein have shown positive effects on short-term weight reduction and glycaemic control. However, the understanding of how dietary macronutrient composition relates to long-term risk of type 2 diabetes is limited. The aim of the present study was to examine intakes of macronutrients, fibre and protein sources in relation to incident type 2 diabetes. In total, 27 140 individuals, aged 45-74 years, from the population-based Malmö Diet and Cancer cohort, were included. Dietary data were collected with a modified diet history method, including registration of cooked meals. During 12 years of follow-up, 1709 incident type 2 diabetes cases were identified. High protein intake was associated with increased risk of type 2 diabetes (hazard ratio (HR) 1.27 for highest compared with lowest quintile; 95 % CI 1.08, 1.49; P for trend = 0.01). When protein consumption increased by 5 % of energy at the expense of carbohydrates (HR 1.20; 95 % CI 1.09, 1.33) or fat (HR 1.21; 95 % CI 1.09, 1.33), increased diabetes risk was observed. Intakes in the highest quintiles of processed meat (HR 1.16; 95 % CI 1.00, 1.36; P for trend = 0.01) and eggs (HR 1.21; 95 % CI 1.04, 1.41; P for trend = 0.02) were associated with increased risk. Intake of fibre-rich bread and cereals was inversely associated with type 2 diabetes (HR 0.84; 95 % CI 0.73, 0.98; P for trend = 0.004). In conclusion, results from the present large population-based prospective study indicate that high protein intake is associated with increased risk of type 2 diabetes. Replacing protein with carbohydrates may be favourable, especially if fibre-rich breads and cereals are chosen as carbohydrate sources.\",\n \"title\": \"High intakes of protein and processed meat associate with increased incidence of type 2 diabetes.\"\n },\n {\n \"docid\": \"MED-825\",\n \"text\": \"BACKGROUND: Some evidence has suggested that a diet with a higher ratio of protein to carbohydrates has metabolic advantages in the treatment of polycystic ovary syndrome (PCOS). OBJECTIVE: The objective of this study was to compare the effect of a high-protein (HP) diet to a standard-protein (SP) diet in women with PCOS. DESIGN: A controlled, 6-mo trial was conducted in 57 PCOS women. The women were assigned through rank minimization to one of the following 2 diets without caloric restriction: an HP diet (>40% of energy from protein and 30% of energy from fat) or an SP diet (<15% of energy from protein and 30% of energy from fat). The women received monthly dietary counseling. At baseline and 3 and 6 mo, anthropometric measurements were performed, and blood samples were collected. RESULTS: Seven women dropped out because of pregnancy, 23 women dropped out because of other reasons, and 27 women completed the study. The HP diet produced a greater weight loss (mean: 4.4 kg; 95% CI: 0.3, 8.6 kg) and body fat loss (mean: 4.3 kg; 95% CI: 0.9, 7.6 kg) than the SP diet after 6 mo. Waist circumference was reduced more by the HP diet than by the SP diet. The HP diet produced greater decreases in glucose than did the SP diet, which persisted after adjustment for weight changes. There were no differences in testosterone, sex hormone-binding globulin, and blood lipids between the groups after 6 mo. However, adjustment for weight changes led to significantly lower testosterone concentrations in the SP-diet group than in the HP-diet group. CONCLUSION: Replacement of carbohydrates with protein in ad libitum diets improves weight loss and improves glucose metabolism by an effect that seems to be independent of the weight loss and, thus, seems to offer an improved dietary treatment of PCOS women.\",\n \"title\": \"Effects of increased dietary protein-to-carbohydrate ratios in women with polycystic ovary syndrome.\"\n },\n {\n \"docid\": \"MED-4612\",\n \"text\": \"Amino acids modulate the secretion of both insulin and glucagon; the composition of dietary protein therefore has the potential to influence the balance of glucagon and insulin activity. Soy protein, as well as many other vegan proteins, are higher in non-essential amino acids than most animal-derived food proteins, and as a result should preferentially favor glucagon production. Acting on hepatocytes, glucagon promotes (and insulin inhibits) cAMP-dependent mechanisms that down-regulate lipogenic enzymes and cholesterol synthesis, while up-regulating hepatic LDL receptors and production of the IGF-I antagonist IGFBP-1. The insulin-sensitizing properties of many vegan diets--high in fiber, low in saturated fat--should amplify these effects by down-regulating insulin secretion. Additionally, the relatively low essential amino acid content of some vegan diets may decrease hepatic IGF-I synthesis. Thus, diets featuring vegan proteins can be expected to lower elevated serum lipid levels, promote weight loss, and decrease circulating IGF-I activity. The latter effect should impede cancer induction (as is seen in animal studies with soy protein), lessen neutrophil-mediated inflammatory damage, and slow growth and maturation in children. In fact, vegans tend to have low serum lipids, lean physiques, shorter stature, later puberty, and decreased risk for certain prominent 'Western' cancers; a vegan diet has documented clinical efficacy in rheumatoid arthritis. Low-fat vegan diets may be especially protective in regard to cancers linked to insulin resistance--namely, breast and colon cancer--as well as prostate cancer; conversely, the high IGF-I activity associated with heavy ingestion of animal products may be largely responsible for the epidemic of 'Western' cancers in wealthy societies. Increased phytochemical intake is also likely to contribute to the reduction of cancer risk in vegans. Regression of coronary stenoses has been documented during low-fat vegan diets coupled with exercise training; such regimens also tend to markedly improve diabetic control and lower elevated blood pressure. Risk of many other degenerative disorders may be decreased in vegans, although reduced growth factor activity may be responsible for an increased risk of hemorrhagic stroke. By altering the glucagon/insulin balance, it is conceivable that supplemental intakes of key non-essential amino acids could enable omnivores to enjoy some of the health advantages of a vegan diet. An unnecessarily high intake of essential amino acids--either in the absolute sense or relative to total dietary protein--may prove to be as grave a risk factor for 'Western' degenerative diseases as is excessive fat intake.\",\n \"title\": \"Vegan proteins may reduce risk of cancer, obesity, and cardiovascular disease by promoting increased glucagon activity.\"\n },\n {\n \"docid\": \"MED-2150\",\n \"text\": \"Previous investigations, of adolescent diet recalled in adulthood, found lower risk for benign breast disease (BBD) with higher intakes of vegetable fat and nuts during high school. We investigate whether vegetable protein and fat, derived from diets reported during pre-adolescence and adolescence, are associated with subsequent risk for BBD in young women. The Growing Up Today Study includes 9,039 females, 9–15 years in 1996, who completed questionnaires annually through 2001, and then in 2003, 2005, 2007, and 2010. Food frequency questionnaires (1996–2001) obtained intake data on a variety of foods. Beginning in 2005, women (18–30 years) reported whether they had ever been diagnosed with BBD that was confirmed by breast biopsy (n = 112 cases). Logistic regression estimated associations between intakes of vegetable protein and fat and biopsy-confirmed BBD. Those individual foods that were the largest contributors of protein and fat in this cohort were also investigated. In analyses of intakes from 1996 through 1998, when our cohort was youngest, vegetable fat (OR = 0.72/(10 gm/day), 95 % CI 0.53–0.98; p = 0.04) was inversely associated with BBD risk. The greatest sources of vegetable fat and protein in these girls were peanut butter, peanuts, nuts, beans (beans, lentils, and soybeans), and corn. A daily serving of any one of these was associated with lower risk (OR = 0.32/(serv/day), 95 % CI 0.13–0.79; p = 0.01). Peanut butter (and nuts) at age 11 years was inversely associated with risk (p = 0.01). In analyses of intakes at age 14 years, vegetable protein was associated with lower BBD risk (OR = 0.64/(10 gm/day), 95 % CI 0.43–0.95; p = 0.03). A daily serving at 14 years of any one of the foods was associated with lower risk (OR = 0.34, 95 % CI 0.16–0.75; p = 0.01), as was peanut butter (and nuts) (p = 0.02). Girls with a family history of breast cancer had significantly lower risk if they consumed these foods or vegetable fat. In conclusion, consumption of vegetable protein, fat, peanut butter, or nuts by older girls may help reduce their risk of BBD as young women.\",\n \"title\": \"Vegetable protein and vegetable fat intakes in pre-adolescent and adolescent girls, and risk for benign breast disease in young women\"\n },\n {\n \"docid\": \"MED-1324\",\n \"text\": \"Six noninsulin-dependent diabetic subjects received meals containing 25 g carbohydrate either as potato or as spaghetti. The meals were repeated with the addition of 25 g protein and with 25 g protein and 25 g fat. Blood glucose and insulin responses were measured for 4 h after the test meal. When carbohydrate was given alone, the blood glucose and serum insulin increments were higher for the potato meal. The addition of protein increased the insulin responses to both carbohydrates and slightly reduced the glycemic response to mashed potato (F = 2.04, p less than 0.05). The further addition of fat reduced the glycemic response to mashed potato (F = 14.63, p less than 0.001) without any change in the blood glucose response to spaghetti (F = 0.94, NS). The different responses to coingestion of protein and fat reduced the difference between the glycemic responses to the two carbohydrates.\",\n \"title\": \"Differential effect of protein and fat ingestion on blood glucose responses to high- and low-glycemic-index carbohydrates in noninsulin-dependent d...\"\n },\n {\n \"docid\": \"MED-1134\",\n \"text\": \"BACKGROUND: The purpose of this article is to evaluate the impact of low protein and high fiber intakes on risk factors of stone recurrence in idiopathic calcium stone formers (ICSFs). METHODS: Ninety-six ICSFs were randomly assigned a low animal protein diet (< 10% of total energy), a high-fiber diet (> 25 g/day), or a usual diet (control group); all patients were recommended to increase their fluid intake. Their daily urine compositions were analyzed at baseline and at four months. Compliance with dietary recommendations was checked by validated food frequency questionnaires. Compliance with total and animal protein intakes was assessed by 24-hour urea and sulfate outputs, respectively. The nutritional intervention (oral instructions, written leaflet, phoning) and food assessment were carried out by a research dietitian. RESULTS: At baseline, diets and the daily urine composition did not differ between the three groups. At four months, while diets differed significantly, the 24-hour output of calcium and oxalate did not differ significantly within and between groups after adjustment for potential confounders (age, sex, and personal and family history of calcium stones) and baseline values. However, as many as 12 out of 31 ICSFs (95% CI, 22 to 58%) assigned to a low animal protein diet achieved a reduction in the urine urea excretion rate of more than 50 mmol/day and also exhibited a significant decrease in urinary calcium excretion that averaged 1.8 mmol/day. A significant correlation between urea and calcium outputs was observed only among patients with hypercalciuria. CONCLUSIONS: These results show that only ICSFs who markedly decrease their animal protein intake, especially those with hypercalciuria, can expect to benefit from dietary recommendations.\",\n \"title\": \"Effects of low animal protein or high-fiber diets on urine composition in calcium nephrolithiasis.\"\n },\n {\n \"docid\": \"MED-4342\",\n \"text\": \"OBJECTIVES: Diet composition has long been suspected to contribute to inflammatory bowel disease (IBD), but has not been thoroughly assessed, and has been assessed only in retrospective studies that are prone to recall bias. The aim of the present study was to evaluate the role of dietary macronutrients in the etiology of IBD in a large prospective cohort. METHODS: The Etude Épidémiologique des femmes de la Mutuelle Générale de l'Education Nationale cohort consists of women living in France, aged 40-65 years, and free of major diseases at inclusion. A self-administered questionnaire was used to record dietary habits at baseline. Questionnaires on disease occurrence and lifestyle factors were completed every 24 months. IBDs were assessed in each questionnaire until June 2005, and subsequently validated using clinical and pathological criteria. We estimated the association between nutrients or foods and IBD using Cox proportional hazards models adjusted for energy intake. RESULTS: Among 67,581 participants (705,445 person-years, mean follow-up since completion of the baseline dietary questionnaire 10.4 years), we validated 77 incident IBD cases. High total protein intake, specifically animal protein, was associated with a significantly increased risk of IBD, (hazards ratio for the third vs. first tertile and 95% confidence interval being 3.31 and 1.41-7.77 (P trend=0.007), and 3.03 and 1.45-6.34 (P trend=0.005) for total and animal protein, respectively). Among sources of animal protein, high consumption of meat or fish but not of eggs or dairy products was associated with IBD risk. CONCLUSIONS: High protein intake is associated with an increased risk of incident IBD in French middle-aged women.\",\n \"title\": \"Animal protein intake and risk of inflammatory bowel disease: The E3N prospective study.\"\n },\n {\n \"docid\": \"MED-4352\",\n \"text\": \"Changes in the concentration and composition of serum VLDL, LDL, and HDL were studied in rabbits transferred from Chow diets to cholesterol-free, semipurified diets containing casein or isolated soy protein. During the first week on the casein diet, there was a marked increase in LDL-cholesterol and these higher levels were maintained during the subsequent 3 weeks of the study. Similar but less marked changes were obtained with the soy protein diet. When the percent composition of the particles was determined, both VLDL and LDL had a higher proportion of cholesterol. Turnover studies indicated that the FCRs for radiolabelled VLDL and LDL were reduced in casein-fed animals compared to those fed soy protein. The elevated LDL levels in casein-fed rabbits were primarily due to a reduction in receptor-mediated catabolism of LDL-apo B. Receptor-independent removal in the two groups was similar. These studies show that the hypercholesterolemia in casein-fed rabbits, compared to those fed soy protein, is associated with cholesterol enrichment of LDL and impaired receptor-dependent removal of LDL-apo B.\",\n \"title\": \"Effects of dietary protein on composition and metabolism of plasma lipoproteins in rabbits.\"\n },\n {\n \"docid\": \"MED-4898\",\n \"text\": \"We examined consumption of animal foods, protein and calcium in relation to risk of prostate cancer among 142 251 men in the European Prospective Investigation into Cancer and Nutrition. Associations were examined using Cox regression, stratified by recruitment centre and adjusted for height, weight, education, marital status and energy intake. After an average of 8.7 years of follow-up, there were 2727 incident cases of prostate cancer, of which 1131 were known to be localised and 541 advanced-stage disease. A high intake of dairy protein was associated with an increased risk, with a hazard ratio for the top versus the bottom fifth of intake of 1.22 (95% confidence interval (CI): 1.07–1.41, Ptrend=0.02). After calibration to allow for measurement error, we estimated that a 35-g day−1 increase in consumption of dairy protein was associated with an increase in the risk of prostate cancer of 32% (95% CI: 1–72%, Ptrend=0.04). Calcium from dairy products was also positively associated with risk, but not calcium from other foods. The results support the hypothesis that a high intake of protein or calcium from dairy products may increase the risk for prostate cancer.\",\n \"title\": \"Animal foods, protein, calcium and prostate cancer risk: the European Prospective Investigation into Cancer and Nutrition\"\n },\n {\n \"docid\": \"MED-1440\",\n \"text\": \"Aging and metabolism-related disorders are risk factors for Alzheimer disease (AD). Since sirtuins may increase the lifespan through regulation of cellular metabolism, we compared the concentration of sirtuin 1 (SIRT1) in the brains of AD patients (n = 19) and controls (n = 22) using Western immunoblots and in situ hybridization. We report a significant reduction of SIRT1 (mRNA: −29%; protein: −45%) in the parietal cortex of AD patients, but not in the cerebellum. Further analyses in a second cohort of 36 subjects confirmed that cortical SIRT1 was decreased in the cortex of AD patients but not in individuals with mild cognitive impairment. SIRT1 mRNA and its translated protein correlated negatively with the duration of symptoms (mRNA: r2 = −0.367; protein: r2 = −0.326) and the accumulation of paired helical filament tau (mRNA: r2 = −0.230; protein: r2 = −0.119), but weakly with insoluble amyloid-β(Aβ42 (mRNA: r2 = −0.090; protein: r2 = −0.072). A significant relationship between SIRT1 levels and global cognition scores proximate to death was also found (r2 = +0.09; p = 0.049). In contrast, cortical SIRT1 levels remained unchanged in a triple-transgenic animal model of AD. Collectively, our results indicate that loss of SIRT1 is closely associated with the accumulation of Aβ and tau in the cerebral cortex of patients with AD.\",\n \"title\": \"SIRT1 Decrease Parallels the Accumulation of tau in Alzheimer Disease\"\n },\n {\n \"docid\": \"MED-2315\",\n \"text\": \"Background The word selectivity describes a drug's ability to affect a particular cell population in preference to others. As part of the current state of art in the search for new therapeutic agents, the property of selectivity is a mode of action thought to have a high degree of desirability. Consequently there is a growing activity in this area of research. Selectivity is generally a worthy property in a drug because a drug having high selectivity may have a dramatic effect when there is a single agent that can be targeted against the appropriate molecular-driver involved in the pathogenesis of a disease. An example is chronic myeloid leukemia (CML). CML has a specific chromosomal abnormality, the Philadelphia chromosome, that results in a single gene that produces an abnormal protein Discussion There is a burgeoning understanding of the cellular mechanisms that control the etiology and pathogeneses of diseases. This understanding both enables and motivates the development of drugs that induce a specific action in a selected cell population; i.e., a targeted treatment. Consequently, drugs that can target distinct molecular targets involved in pathologic/pathogenetic processes, or signal-transduction pathways, are being developed. However, in most cases, diseases involve multiple abnormalities. A disease may be associated with more than one dysfunctional protein and these may be out-of-balance with each other. Likewise a drug might strongly target a protein that shares a similar active domain with other proteins. A drug may also target pleiotropic cytokines, or other proteins that have multi-physiological functions. In this way multiple normal cellular pathways can be simultaneously influenced. Long term experience with drugs supposedly designed for only a single target, but which unavoidably involve other functional effects, is uncovering the fact that molecular targeting is not medically flawless. Summary We contend that an ideal drug may be one whose efficacy is based not on the inhibition of a single target, but rather on the rebalancing of the several proteins or events, that contribute to the etiology, pathogeneses, and progression of diseases, i.e., in effect a promiscuous drug. Ideally, if this could be done at minimum drug concentration, side effects could be minimized. Corollaries to this argument are that the growing fervor for researching truly selective drugs may be imprudent when considering the totality of responses; and that the expensive screening techniques used to discover these, may be both medically and financially inefficient.\",\n \"title\": \"Promiscuous drugs compared to selective drugs (promiscuity can be a virtue)\"\n },\n {\n \"docid\": \"MED-2603\",\n \"text\": \"FAS-associated protein with death domain (FADD) is the key adaptor protein transmitting apoptotic signals mediated by the main death receptors (DRs). Besides being an essential instrument in cell death, FADD is also implicated in proliferation, cell cycle progression, tumor development, inflammation, innate immunity, and autophagy. Recently, many of these new functions of FADD were shown to be independent of DRs. Moreover, FADD function is dictated by protein localization and phosphorylation state. Thus, FADD is a crucial and unique controller of many essential cellular processes. The full understanding of the networks dictating the ultimate function of FADD may provide a new paradigm for other multifaceted proteins. Copyright 2010 Elsevier Ltd. All rights reserved.\",\n \"title\": \"FADD: a regulator of life and death.\"\n },\n {\n \"docid\": \"MED-2136\",\n \"text\": \"Prostate cancer (PCa) is dependent on androgen receptor signaling and aberrations of the PI3K-Akt-mTORC1 pathway mediating excessive and sustained growth signaling. The nutrient-sensitive kinase mTORC1 is upregulated in nearly 100% of advanced human PCas. Oncogenic mTORC1 signaling activates key subsets of mRNAs that cooperate in distinct steps of PCa initiation and progression. Epidemiological evidence points to increased dairy protein consumption as a major dietary risk factor for the development of PCa. mTORC1 is a master regulator of protein synthesis, lipid synthesis and autophagy pathways that couple nutrient sensing to cell growth and cancer. This review provides evidence that PCa initiation and progression are promoted by cow´s milk, but not human milk, stimulation of mTORC1 signaling. Mammalian milk is presented as an endocrine signaling system, which activates mTORC1, promotes cell growth and proliferation and suppresses autophagy. Naturally, milk-mediated mTORC1 signaling is restricted only to the postnatal growth phase of mammals. However, persistent consumption of cow´s milk proteins in humans provide highly insulinotropic branched-chain amino acids (BCAAs) provided by milk´s fast hydrolysable whey proteins, which elevate postprandial plasma insulin levels, and increase hepatic IGF-1 plasma concentrations by casein-derived amino acids. BCAAs, insulin and IGF-1 are pivotal activating signals of mTORC1. Increased cow´s milk protein-mediated mTORC1 signaling along with constant exposure to commercial cow´s milk estrogens derived from pregnant cows may explain the observed association between high dairy consumption and increased risk of PCa in Westernized societies. As well-balanced mTORC1-signaling plays an important role in appropriate prostate morphogenesis and differentiation, exaggerated mTORC1-signaling by high cow´s milk consumption predominantly during critical growth phases of prostate development and differentiation may exert long-term adverse effects on prostate health. Attenuation of mTORC1 signaling by contemporary Paleolithic diets and restriction of dairy protein intake, especially during mTORC1-dependent phases of prostate development and differentiation, may offer protection from the most common dairy-promoted cancer in men of Western societies.\",\n \"title\": \"The impact of cow's milk-mediated mTORC1-signaling in the initiation and progression of prostate cancer\"\n },\n {\n \"docid\": \"MED-4852\",\n \"text\": \"OBJECTIVES: A dietary link to rheumatoid arthritis (RA) has been suspected and an influence on arthritic symptoms by different diets has been reported. Our primary aim was to record the self-experienced adverse food reactions in patients with RA. A secondary aim was to relate self-experienced adverse reactions to dairy produce and wheat to the local mucosal reactivity observed after rectal challenge with cow's milk protein (CM) and wheat gluten. METHODS: A questionnaire about self-experienced adverse reaction to food was sent to 347 RA patients. Rectal challenge with CM and gluten was performed in 27 of these patients and in healthy controls (n = 18). After a 15-h challenge the mucosal production of nitric oxide (NO) and the mucosal release of myeloperoxidase (MPO) and eosinophil cationic protein (ECP) were measured by using the mucosal patch technique. RESULTS: Twenty-seven per cent of the RA patients reported food intolerance (FI) to various foods, and in particular to CM, meat, and wheat gluten. Strong mucosal reactivity to CM was observed in 11% of the patients. Moderately increased mucosal reactivity to CM and gluten was found in 22% and 33%, respectively, of the patients. No relationship was found between self-experienced adverse reactions to CM or gluten and mucosal reactivity to these proteins. CONCLUSIONS: Perceived FI is reported frequently by RA patients, with a prevalence similar to that reported previously in the general population. Mucosal reactivity to CM and gluten is seen in a minor fraction of RA patients and is not related to the frequently perceived intolerance to these proteins.\",\n \"title\": \"Self-reported food intolerance and mucosal reactivity after rectal food protein challenge in patients with rheumatoid arthritis.\"\n }\n]"}}},{"rowIdx":184,"cells":{"query_id":{"kind":"string","value":"7085"},"query":{"kind":"string","value":"Canadian Citizen and Non Resident for tax purposes"},"positive_passages":{"kind":"list like","value":[{"docid":"456968","text":"However, you might have to pay taxes on capital gains if these stocks were acquired during your prior residency.","title":""}],"string":"[\n {\n \"docid\": \"456968\",\n \"text\": \"However, you might have to pay taxes on capital gains if these stocks were acquired during your prior residency.\",\n \"title\": \"\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"518624","text":"\"The other answer has mentioned \"\"factual resident\"\", and you have raised the existence of a U.S./Canada tax treaty in your comment, and provided a link to a page about determining residency. I'd like to highlight part of the first link: You are a factual resident of Canada for tax purposes if you keep significant residential ties in Canada while living or travelling outside the country. The term factual resident means that, although you left Canada, you are still considered to be a resident of Canada for income tax purposes. Notes If you have established ties in a country that Canada has a tax treaty with and you are considered to be a resident of that country, but you are otherwise a factual resident of Canada, meaning you maintain significant residential ties with Canada, you may be considered a deemed non-resident of Canada for tax purposes. [...] I'll emphasize that \"\"considered to be a resident of Canada for income tax purposes\"\" means you do need to file Canadian income tax returns. The Notes section does indicate the potential treaty exemption that you mentioned, but it is only a potential exemption. Note the emphasis (theirs, not mine) on the word \"\"may\"\" in the last paragraph above. Please don't assume \"\"may\"\" is necessarily favorable with respect to your situation. The other side of the \"\"may\"\" coin is \"\"may not\"\". The Determining your residency status page you mentioned in your comment says this: If you want the Canada Revenue Agency's opinion on your residency status, complete either Form NR74, Determination of Residency Status (Entering Canada) or Form NR73, Determination of Residency Status (Leaving Canada), whichever applies, and send it to the International and Ottawa Tax Services Office. To get the most accurate opinion, provide as many details as possible on your form. So, given your ties to Canada, I would suggest that until and unless you have obtained an opinion from the Canada Revenue Agency on your tax status, you would be making a potentially unsafe assumption if you yourself elect not to file your Canadian income tax returns based on your own determination. You could end up liable for penalties and interest if you don't file while you are outside of Canada. Tax residency in Canada is not a simple topic. For instances, let's have a look at S5-F1-C1, Determining an Individual’s Residence Status. It's a long page, but here's one interesting piece: 1.44 The Courts have stated that holders of a United States Permanent Residence Card (otherwise referred to as a Green Card) are considered to be resident in the United States for purposes of paragraph 1 of the Residence article of the Canada-U.S. Tax Convention. For further information, see the Federal Court of Appeal's comments in Allchin v R, 2004 FCA 206, 2004 DTC 6468. [...] ... whereas you are in the U.S. on a TN visa, intended to be temporary. So you wouldn't be exempt just on the basis of your visa and the existence of the treaty. The CRA would look at other circumstances. Consider the \"\"Centre of vital interests test\"\": Centre of vital interests test [...] “If the individual has a permanent home in both Contracting States, it is necessary to look at the facts in order to ascertain with which of the two States his personal and economic relations are closer. Thus, regard will be had to his family and social relations, his occupations, his political, cultural or other activities, his place of business, the place from which he administers his property, etc. The circumstances must be examined as a whole, but it is nevertheless obvious that considerations based on the personal acts of the individual must receive special attention. If a person who has a home in one State sets up a second in the other State while retaining the first, the fact that he retains the first in the environment where he has always lived, where he has worked, and where he has his family and possessions, can, together with other elements, go to demonstrate that he has retained his centre of vital interests in the first State.” [emphasis on last sentence is mine] Anyway, I'm acquainted with somebody who left Canada for a few years to work abroad. They assumed that living in the other country for that length of time (>2 years) meant they were non-resident here and so did not have to file. Unfortunately, upon returning to Canada, the CRA deemed them to have been resident all that time based on significant ties maintained, and they subsequently owed many thousands of dollars in back taxes, penalties, and interest. If it were me in a similar situation, I would err on the side of caution and continue to file Canadian income taxes until I got a determination I could count on from the people that make the rules.\"","title":""},{"docid":"594784","text":"If you're a US citizen/resident - you pay taxes on your worldwide income regardless of where you live. The logic is that Americans generally don't agree to the view that there's more than one country in the world. If you're non-US person, not physically present in the US, and provide contract work for a US employer - you generally don't pay taxes in the US. The logic is that the US doesn't actually have any jurisdiction over that money, you didn't earn it in the US. That said, your employer might withheld tax and remit it to the IRS, and you'll have to chase them for refund. If you receive income from the US rental property or dividends from a US company - you pay income tax to the US on that income, and then bargain with your home tax authority on refunds of the difference between what you paid in the US and what you should have paid at home. You can also file non-resident tax return in the US to claim what you have paid in excess. The logic is that the money sourced in the US should be taxed in the US. You earned that money in the US. There are additional rules to more specific situation, and there are also bilateral treaties between countries (including a US-Canadian treaty) that supersede national laws. Bottom line, not only that each country has its own laws, there are also different laws for different situations, and if some of the international treaties apply to you - it further complicates the situation. If something is not clear - get a professional advice form a tax accountant licensed in the relevant jurisdictions (in your case - any of the US states, and the Canadian province where you live).","title":""},{"docid":"347186","text":"Tax liability in US: You would need to determine if you are a resident alien or non resident alien. Resident alien are taxed normally as per US citizens. For the annual remuneration you have quoted it would be in the range of 25%. Refer http://www.moneychimp.com/features/tax_brackets.htm To determine if you are resident alien or non resident alien, you need to be present for certain period in US. There is also an exemption even if you meet this you can still be treated as non resident alien if your tax home is outside US [India in this case] Refer to the link for details to determine your category, the durations are for number of days in financial year, hence it matters when you are in US and the exact durations. http://www.irs.gov/taxtopics/tc851.html Also note that if you are assessed as resident alien, even the income from India will be taxed in US unless you declare there is no income in India. Tax liability in India: The tax liability in India would be depending on your NRI status. This again is tied to the financial year and the number of days you are in country. While the year you are going out of India you need to be away for atleast 183 days for you be considred are NRI. So if you are treated as Indian resident, you would have to pay tax in India on entire income. In the worst case, depending on the period you travel and the dates you travel, you could get classified as citizen in US as well as India and have to pay tax at both places. India and US do not have a dual tax avoidance treaty for individuals. Its there for certain category like small business and certain professions like teacher, research etc.","title":""},{"docid":"272173","text":"Assuming you are Indian Citizen / Resident for Tax purposes. Your friend in US Citizen / Resident for tax purposes. As you are borrowing these funds and returning, this would NOT be treated as Gift but as Loan. Ensure that you have the right documentation in place. There is no tax when you receive the funds/loan or rebate when you pay back the loan. From India FEMA (Foreign Exchange Management Act) point of view, if you take loan from friends, you cannot by default repatriate funds. You have to take special permission to repatriate the funds out of India.","title":""},{"docid":"570639","text":"\"Transferring the money or keeping it in US does has no effect on taxes. Your residency status has. Assuming you are Resident Alien in US for tax purpose and have paid the taxes to IRS and you are \"\"Non-Resident\"\" Indian for tax purposes in India as you are more than 182 outside India. How would it effect my Tax in US and India If you are \"\"Non-Resident\"\" in India for tax purposes, there is no tax liability of this in India. I have transferred an amount of approx 15-20k$ to Indian Account (not NRE) By RBI regulation, if you are \"\"Non-Resident\"\" then you should get your savings account converted to \"\"NRO\"\". You may not may not choose to open an NRE account. To keep the paper work clear it helps that you open an NRE account in India. Any investment needed ? Where do i need to declare if any ? These are not relevant. Note any income generated in India, i.e. interest in Savings account / FDs / Rent etc; taxes need to be paid in India and declared in US and taxes paid in US as well. There is some relief under DTAA. There are quite a few question on this site that will help you clarify what needs to be done.\"","title":""},{"docid":"575899","text":"Found a great article (with bibliography) that covers taxation on investment activity by non resident aliens - even covers the special 15% tax on dividends for Canadian residents. It's (dividend tax rate) generally 30% for other NRAs (your 2nd question). And it confirmed my suspicion that there are no capital gains taxes for NRAs. (1st Q) Source: http://invest-faq.com/articles/tax-non-us-nat.html","title":""},{"docid":"352266","text":"Canada doesn't tax non-residents on income earned/incurred outside of Canada. So, your sister should start with this page to determine the residency status. If she is indeed determined to be non-resident - she should look here to see her obligations. If all she earns she earns outside of Canada - her obligations will be very little, if at all. This is similar to almost any other country in the world, with the notable exception of the United States of America. US citizens are taxed regardless of their residency status, everywhere in the world on worldwide income (unless tax treaty says otherwise).","title":""},{"docid":"214690","text":"Gifts from your parents are not treated as income for tax purposes. You should not include that in your subsidy calculation. If you are here on a student-visa and have been in the US for less than 5 years, then you are considered a non-resident alien, and you are not required to buy a qualified plan through the insurance marketplace. You might be able to get a cheaper student plan through your school, but the subsidy might be enough that it's still worth it when calculated correctly. If you are a resident-alien or you are a citizen of the US, then you are required to get coverage, though you can choose not to purchase coverage and pay the tax for not having creditable coverage. That tax cannot be collected by the IRS unless you have already had federal tax withheld. They can only confiscate your tax return money to recoup that money. I don't have enough information to recommend one way or the other what you should do, but I would bet that if you recalculated your subsidy without including your parents income it would cover the majority of the cost. You should also consider applying for Medicaid if you meet the eligibility requirements in your state.","title":""},{"docid":"298796","text":"The finance team from your company should be able to advise you. From what I understand you are Indian Citizen for Tax purposes. Any income you receive globally is taxable in India. In this specific case you are still having a Employee relationship with your employer and as such the place of work does not matter. You are still liable to pay tax in India on the salary. If you are out of India for more than 182 days, you can be considered as Non-Resident from tax point of view. However this clause would not be of any benefit to you as are having a Employee / Employer relationship and being paid in India. Edit: This is only about the India portion of taxes. There maybe a UK protion of it as well, plus legally can you work and your type of Visa in UK may have a bearing on the answer","title":""},{"docid":"228445","text":"Yes, you have to file a tax return in Canada. Non residents that have earned employment income in Canada are required to file a Canadian personal income tax return. Usually, your employer will have deducted sufficient taxes from your pay-cheques, resulting in a tax refund upon filing your Canadian tax return. You will also receive a tax credit on your US tax return for taxes paid in Canada.","title":""},{"docid":"457455","text":"It essentially works the same. Some states don't have any income taxes at all (like Florida or Wyoming), some only tax income derived in the state, and some tax worldwide income (like New York or California), similarly to the Federal income taxes. However, if you're living abroad (i.e.: you're a citizen or resident of a foreign country and you live there), you're not considered resident by most of the states (check with your state for specific definitions) for most, if not all, the time of your residency abroad. In such case - you don't pay state taxes, only Federal. You have to remember that foreign income exclusion doesn't apply to the income from your 401k, so you pay the taxes as if you're in the US. You can not use foreign taxes credit as well (but depending on the tax treaty with the country you're moving to, your 401k income might not be taxable there). In some cases you may end up with double taxation: US will tax your 401k income as you're a US citizen and the income is derived from the US sources, and the foreign country will tax the income based on its own laws. This is not a tax advice, and this answer was not intended or written to be used, and it cannot be used by any taxpayer, for the purpose of avoiding penalties that may be imposed on the taxpayer.","title":""},{"docid":"241048","text":"Taxability depends on your tax residency status. Assuming you are non-resident Indian for tax purposes, then your income is non taxable in India. If you keep the money in Saudi or transfer to India it would be same and non taxable","title":""},{"docid":"360773","text":"Though non-resident Indians (NRIs) earn their living abroad, their obligation to file tax returns in India doesn't end. With the July 31 deadline for filing returns barely a month away, NRIs need to gear up to file their return if they have income in India that exceeds the basic exemption limit. How to Determine tax residency status: An NRI first needs to determine his tax residency status, that is, whether he falls in the category of resident or non-resident Indian (NRI) for tax purposes. While there may be no ambiguity regarding the status of an NRI who has lived abroad for a long time, those who have moved abroad recently or have returned to India after a long stay abroad need to ascertain their residency status properly.","title":""},{"docid":"475115","text":"Per the IRS instructions on filing as Head of Household as a Citizen Living Abroad, if you choose to file only your own taxes, and you qualify for Head of Household without them, the IRS does not consider you married: If you are a U.S. citizen married to a nonresident alien you may qualify to use the head of household tax rates. You are considered unmarried for head of household purposes if your spouse was a nonresident alien at any time during the year and you do not choose to treat your nonresident spouse as a resident alien. However, your spouse is not a qualifying person for head of household purposes. You must have another qualifying person and meet the other tests to be eligible to file as a head of household. As such, you could file as Married Filing Separately (if you have no children) or Head of Household (if you have one or more children, a parent, etc. for whom you paid more than half of their upkeep - see the document for more information). You also may choose to file as Married Filing Jointly, if it benefits you to do so (it may, if she earns much less than you). See the IRS document Nonresident Spouse Treated As Resident for more information. If you choose to treat her as a resident, then you must declare her worldwide income. In some circumstances this will be beneficial for you, if you earn substantially more than her and it lowers your tax rate overall to do so. Married Filing Separately severely limits your ability to take some deductions and credits, so it's well worth seeing which is better.","title":""},{"docid":"367562","text":"I can only answer about the U.S. For question 2, I believe the answer is no. If you are a non-resident alien for tax purposes, then only income connected to the U.S. is reported as income on the tax return. Unless there were any non-deductible contributions to your pre-tax IRAs, when you convert to Roth IRA, the entire amount of the conversion is added to your income. So the tax consequence is the same as if you had that much additional U.S. income. If you are a non-resident alien with no other income in the U.S., then the income you have to report on your U.S. tax return will basically consist of the conversion. Non-resident aliens do not have a standard deduction. However, all people have a personal exemption. If we take 2013 as an example, the exemption is $3900 per person. We will assume that you will file as single or married filing separately (non-resident aliens cannot file as married filing jointly). The first $3900 of income is covered by the exemption, and is not counted in taxable income. For single and MFS, the next $8925 of income is taxed at 10%, then next $27325 of income is taxed at 15%, and so on. So if you convert less than the personal exemption amount every year ($3900 in 2013), then in theory you do not pay any taxes. If you convert a little bit more, then some of the conversion will be taxed at 10%, etc.","title":""},{"docid":"30343","text":"\"You've asked a number of questions. I can answer a few. I've quoted your question before each answer. What are the ins and outs of a foreigner like myself buying rental property in Canada? This is a pretty broad question which can address location, finances, basic suggestions etc. Here's some things to consider: Provincial considerations: Some ins and outs will depend on what province you are considering and what area in that Province. If you plan on owning in Montreal, for example, that's in the province of Quebec and that means you (or someone) will need to be able to operate in the French language. There are other things that might be different from province to province. See stat info below. Canadian vs. US Dollar: Now might be a great time to buy property in Canada since the Canada dollar is weak right now. To give you an idea, at a non-cash rate of 1.2846, a little over $76,000 US will get you over $100k Canadian. That's using the currency converter at rbcroyalbank.com. Taxes for non-resident rental property owners: According to the T4144 Income Tax Guide for Electing Under Section 216 – 2015: \"\"When you receive rental income from real or immovable property in Canada, the payer, such as the tenant or a property manager, has to withhold non-resident tax at the rate of 25% on the gross rental income paid or credited to you. The payer has to pay us the tax on or before the 15th day of the month following the month the rental income is paid or credited to you.\"\" If you prefer to send a separate Canadian tax return, you can choose to elect under section 216 of the Income Tax Act. A benefit of this way is that \"\"electing under section 216 allows you to pay tax on your net Canadian-source rental income instead of on the gross amount. If the non-resident tax withheld by the payer is more than the amount of tax payable calculated on your section 216 return, [they] will refund the excess to you.\"\" You can find this guide at Canada Revenue's site: http://www.cra-arc.gc.ca/E/pub/tg/t4144/README.html Stats: A good place for stats is the Canada Mortgage and Housing Corporation (CMHC). So, if you are interesting in vacancy rates for example, you can see a table that will show you that the vacancy rate in Ontario is 2.3% and in British Columbia it's 1.5%. However, in New Brunswick it's 8%. The rate for metropolitan areas across Canada is 2.8%. If you want to see or download this table showing the vacancy rates by province and also by metropolitan areas, go to the Canada Mortgage and Housing Corporation site http://www.cmhc.ca/housingmarketinformation/. You can get all sorts of housing information, reports and market information there. I've done well with Condos/Town-homes and would be interested in the same thing over there. Is it pretty much all the same? See the stat site mentioned above to get market info about condos, etc. What are the down payment requirements? For non-owner occupied properties, the down payment is at least 20%. Update in response to comments about being double taxed: Regarding being taxed on income received from the property, if you claim the foreign tax credit you will not be double taxed. According to the IRS, \"\"The foreign tax credit intends to reduce the double tax burden that would otherwise arise when foreign source income is taxed by both the United States and the foreign country from which the income is derived.\"\" (from IRS Topic 856 - Foreign Tax Credit) About property taxes: From my understanding, these would not be claimed for the foreign tax credit but can be deducted as business expenses. There are various exceptions and stipulations based on your circumstance, so you need to read Publication 856 - Foreign Tax Credit for Individuals. Here's an excerpt: \"\"In most cases, only foreign income taxes qualify for the foreign tax credit. Other taxes, such as foreign real and personal property taxes, do not qualify. But you may be able to deduct these other taxes even if you claim the foreign tax credit for foreign income taxes. In most cases, you can deduct these other taxes only if they are expenses incurred in a trade or business or in the production of income. However, you can deduct foreign real property taxes that are not trade or business expenses as an itemized deduction on Schedule A (Form 1040).\"\" Disclaimers: Sources: IRS Topic 514 Foreign Tax Credit and Publication 856 Foreign Tax Credit for Individuals\"","title":""},{"docid":"259602","text":"I can't give you a specific answer because I'm not a tax accountant, so you should seek advice from a tax professional with experience relevant to your situation. This could be a complicated situation. That being said, one place you could start is the Canada Revenue Agency's statement on investment income, which contains this paragraph: Interest, foreign interest and dividend income, foreign income, foreign non-business income, and certain other income are all amounts you report on your return. They are usually shown on the following slips: T5, T3, T5013, T5013A To avoid double taxation, Canada and the US almost certainly have a foreign tax treaty that ensures you are only taxed in your country of residence. I'm assuming you're a resident of Canada. Also, this page states that: If you received foreign interest or dividend income, you have to report it in Canadian dollars. Use the Bank of Canada exchange rate that was in effect on the day you received the income. If you received the income at different times during the year, use the average annual exchange rate. You should consult a tax professional. I'm not a tax professional, let alone one who specializes in the Canadian tax system. A professional is the only one you should trust to answer your question with 100% accuracy.","title":""},{"docid":"481601","text":"In theory, when you obtained ownership of your USD cash as a Canadian resident [*resident for tax purposes, which is generally a quicker timeline than being resident for immigration purposes], it is considered to have been obtained by you for the CAD equivalent on that date. For example if you immigrated on Dec 31, 2016 and carried $10k USD with you, when the rate was ~1.35, then Canada deems you to have arrived with $13.5k CAD. If you converted that CAD to USD when the rate was 1.39, you would have received 13.9k CAD, [a gain of $400 to show as income on your tax return]. Receiving the foreign inheritances is a little more complex; those items when received may or may not have been taxable on that day. However whether or not they were taxable, you would calculate a further gain as above, if the fx rate gave you more CAD when you ultimately converted it. If the rate went the other way and you lost CAD-value, you may or may not be able to claim a loss. If it was a small loss, I wouldn't bother trying to claim it due to hassle. If it's a large loss, I would be very sure to research thoroughly before claiming, because something like that probably has a high chance of being audited.","title":""},{"docid":"84528","text":"\"Tax US corporate \"\"persons (citizens)\"\" under the same regime as US human persons/citizens, i.e., file/pay taxes on all income earned annually with deductions for foreign taxes paid. Problem solved for both shareholders and governments. [US Citizens and Resident Aliens Abroad - Filing Requirements](https://www.irs.gov/individuals/international-taxpayers/us-citizens-and-resident-aliens-abroad-filing-requirements) >If you are a U.S. citizen or resident alien living or traveling outside the United States, **you generally are required to file income tax returns, estate tax returns, and gift tax returns and pay estimated tax in the same way as those residing in the United States.** Thing is, we know solving this isn't the point. It is to misdirect and talk about everything, but the actual issues, i.e., the discrepancy between tax regimes applied to persons and the massive inequality it creates in tax responsibility. Because that would lead to the simple solutions that the populace need/crave. My guess is most US human persons would LOVE to pay taxes only on what was left AFTER they covered their expenses.\"","title":""},{"docid":"235266","text":"In the general case if you have income coming in from a foreign source you need to declare it on your Canadian tax form, and nominally pay tax on it. However Canada has a tax agreement with the UK to ensure that you are not taxed twice. You also declare how much tax you have paid to the UK, and that is deducted from your Canadian tax bill. You may need to consult a tax professional, or maybe just read the Revenue Canada website to get the details. If you are holding this money for a friend, then you may find that this does not count as income to you. If you are getting it transferred to you in Canada, and then immediately passed on to your friend, it probably doesn't count as income (though again a tax professional will probably be helpful). This would mean you don't have to pay Canadian tax. But it's also a bummer because you've paid UK tax, which you might also have avoided, and you can't get that back without a lot of form filling. If this is going to be an ongoing situation, and the amount is significant, then you might look at getting your friend's money (and any you have in a UK account yourself) transferred to an offshore account, where UK tax is not automatically deducted. Most UK banks will do this for non-UK residents.","title":""},{"docid":"288993","text":"To build a US credit record, you need a Social Security Number (SSN), which is now not available for most non-residents. An alternative is an ITIN number, which is now available to non-residents only if they have US income giving a reason to file a US tax return (do you really want to get into all that...). Assuming you did have a reason to get a ITIN (one reason would be if you sold some ebooks via Amazon US, and need a withholding refund under the tax treaty), then recent reports on Flyertalk give mixed results on whether it's possible to get a credit card with an ITIN, and whether that would build a credit record. It does sound possible in some cases. A credit record in any other country would not help. You would certainly need a US address, and banks are increasingly asking for a physical address, rather than just a mailbox. Regardless, building this history would be of limited benefit to you if you later became a US resident, at that point you would be eligible for a new SSN (different from the ITIN) and have to largely start again. If getting a card is the aim, rather than the credit record, you may find some banks that will offer a secured card (or a debit card), to non-residents, especially in areas with lots of Canadian visitors (border, Florida, Arizona). You'd find it a lot easier with a US address though, and you'd need to shop around a lot of banks in person until you find one with the right rules. Most will simply avoid anyone without an SSN.","title":""},{"docid":"265861","text":"This answer applies only to corporation tax, not income tax. Different things, income tax is much higher. 12.5% is the low rate for corporation tax. The standard rate is 25%. Or if you're Apple 0%. Like many countries Ireland will only consider you eligible for the low rate of corporation tax if you (your Irish company) can demonstrably prove yourself resident in Ireland. This is more than just address, and you must be able to evidence that your staff work there, your directors are both European Economic Area citizens and have their board meetings in Ireland, and most importantly that they run the company from Ireland, etc. If you're a one man corporation, unless you want to live in Ireland, it's not going to work. Referring to the Irish government's website: The term 'residence' was not, until recently, defined in law. The general rule was that companies, whose 'central management and control' was exercised in the State, were treated as resident here. This rule or test emerged as a result of judicial decisions set down in case law. Factors to be taken into account in establishing where the company's central management and control lie include, for example, where the important questions of company policy are determined, where the majority of directors reside, where the negotiation of major contracts is undertaken and where the company's head office is located. Long story short: An Irish incorporated company is not treated as Irish resident for tax purposes if it is a 'relevant company' ... A Relevant Company is a company that ... is ultimately controlled by persons resident in the EU or in a country with which Ireland has concluded a double taxation treaty","title":""},{"docid":"141458","text":"\"Not really, no. The assumption you're making—withdrawals from a corporation are subject to \"\"[ordinary] income tax\"\"—is simplistic. \"\"Income tax\"\" encompasses many taxes, some more benign than others, owing to credits and exemptions based on the kind of income. Moreover, the choices you listed as benefits in the sole-proprietor case—the RRSP, the TFSA, and capital gains treatment for non-registered investments—all remain open to the owner of a small corporation ... the RRSP to the extent that the owner has received salary to create contribution room. A corporation can even, at some expense, establish a defined benefit (DB) pension plan and exceed individual RRSP contribution limits. Yes, there is a more tax-efficient way for small business owners to benefit when it comes time to retirement. Here is an outline of two things I'm aware of: If your retirement withdrawals from your Canadian small business corporation would constitute withdrawal from the corporation's retained earnings (profits), i.e. income to the corporation that had already been subject to corporate income tax in prior years, then the corporation is able to declare such distributions as dividends and issue you a T5 slip (Statement of Investment Income) instead of a T4 slip (Statement of Remuneration Paid). Dividends received by Canadian residents from Canadian corporations benefit from the Dividend Tax Credit (DTC), which substantially increases the amount of income you can receive without incurring income tax. See TaxTips.ca - Non-eligible (small business) dividend tax credit (DTC). Quote: For a single individual with no income other than taxable Canadian dividends which are eligible for the small business dividend tax credit, in 2014 approximately $35,551 [...] could be earned before any federal* taxes were payable. * Provincial DTCs vary, and so combined federal/provincial maximums vary. See here. If you're wondering about \"\"non-eligible\"\" vs. \"\"eligible\"\": private small business corporation dividends are generally considered non-eligible for the best DTC benefit—but they get some benefit—while a large public corporation's dividends would generally be considered eligible. Eligible/non-eligible has to do with the corporation's own income tax rates; since Canadian small businesses already get a big tax break that large companies don't enjoy, the DTC for small businesses isn't as good as the DTC for public company dividends. Finally, even if there is hardly any same-year income tax advantage in taking dividends over salary from an active small business corporation (when you factor in both the income tax paid by the corporation and the individual), dividends still allow a business owner to smooth his income over time, which can result in a lower lifetime average tax rate. So you can use your business as a retained earnings piggy bank to spin off dividends that attract less tax than ordinary income. But! ... if you can convince somebody to buy your business from you, then you can benefit from the lifetime capital gains exemption of up to $800,000 on qualifying small business shares. i.e. you can receive up to $800K tax-free on the sale of your small business shares. This lifetime capital gains exemption is a big carrot—designed, I believe, to incentivize Canadian entrepreneurs to develop going-concern businesses that have value beyond their own time in the business. This means building things that would make your business worth buying, e.g. a valued brand or product, a customer base, intellectual property, etc. Of course, there are details and conditions with all of what I described, and I am not an accountant, so please consult a qualified, conflict-free professional if you need advice specific to your situation.\"","title":""},{"docid":"102287","text":"\"I'm assuming that by saying \"\"I'm a US resident now\"\" you're referring to the residency determination for tax purposes. Should I file a return in the US even though there is no income here ? Yes. US taxes its residents for tax purposes (which is not the same as residents for immigration or other purposes) on worldwide income. If yes, do I get credits for the taxes I paid in India. What form would I need to submit for the same ? I am assuming this form has to be issued by IT Dept in India or the employer in India ? The IRS doesn't require you to submit your Indian tax return with your US tax return, however they may ask for it later if your US tax return comes under examination. Generally, you claim foreign tax credits using form 1116 attached to your tax return. Specifically for India there may also be some clause in the Indo-US tax treaty that might be relevant to you. Treaty claims are made using form 8833 attached to your tax return, and I suggest having a professional (EA/CPA licensed in your State) prepare such a return. Although no stock transactions were done last year, should I still declare the value of total stocks I own ? If so what is an approx. tax rate or the maximum tax rate. Yes, this is done using form 8938 attached to your tax return and also form 114 (FBAR) filed separately with FinCEN. Pay attention: the forms are very similar with regard to the information you provide on them, but they go to different agencies and have different filing requirements and penalties for non-compliance. As to tax rates - that depends on the types of stocks and how you decide to treat them. Generally, the tax rate for PFIC is very high, so that if any of your stocks are classified as PFIC - you'd better talk to a professional tax adviser (EA/CPA licensed in your State) about how to deal with them. Non-PFIC stocks are dealt with the same as if they were in the US, unless you match certain criteria described in the instructions to form 5471 (then a different set of rules apply, talk to a licensed tax adviser). I will be transferring most of my stock to my father this year, will this need to be declared ? Yes, using form 709. Gift tax may be due. Talk to a licensed tax adviser (EA/CPA licensed in your State). I have an apartment in India this year, will this need to be declared or only when I sell the same later on ? If there's no income from it - then no (assuming you own it directly in your own name, for indirect ownership - yes, you do), but when you sell you will have to declare the sale and pay tax on the gains. Again, treaty may come into play, talk to a tax adviser. Also, be aware of Section 121 exclusion which may make it more beneficial for you to sell earlier.\"","title":""},{"docid":"157712","text":"I am a US citizen and I want to transfer some amount 10 lakhs+ to my brother from my NRE account in India to his account. My brother is going to purchase something for his business. He is going to return my amount after 3-4 Months From the description it looks like you would like to loan to your brother on repatriation basis. Yes this is allowed. See the RBI Guide here and here for more details. There are some conditions; (iv) Scheme for raising loans from NRIs on repatriation basis Borrowings not exceeding US$ 2,50,000 or its equivalent in foreign exchange by an individual resident in India from his close relatives resident outside India, subject to the conditions that - a) the loan is free of interest; b) the minimum maturity period of the loan is seven years; c) The amount of loan is received by inward remittance in free foreign exchange through normal banking channels or by debit to the NRE/FCNR account of the non-resident lender; d) The loan is utilised for the borrower's personal purposes or for carrying on his normal business activity but not for carrying on agricultural/plantation activities, purchase of immovable property or shares/debentures/bonds issued by companies in India or for re-lending. Although it is mentioned as Seven years, this is revised to one year. Since he cannot deposit into my NRE account I guess he has to deposit it into my NRO account. A repatriate-able loan as above can be deposited into NRE Account. Is there any illegality here doing such transaction? No. Please ensure proper paper work to show this as loan and document the money trail. Also once I get my money in NRO account do I need to pay taxes in India on the money he deposited? This question does not arise.","title":""},{"docid":"14817","text":"\"All the other answers posted thus far discuss matters from the perspective of US tax laws and are unanimous in declaring that what the OP wants to do is indeed a very bad idea. I fully agree: it is a bad idea from the perspective of US tax laws, and is likely a bad idea from the perspective of Indian tax laws too, but what the OP wants to do is (or used to be) common practice in India. In more recent times, India has created a Permanent Account Number (\"\"PAN number\"\") for each taxpayer for income tax purposes, and each bank account or investment must have the owner's (or first-named owner's, in case of a joint account) PAN number associated with it. This most likely has decreased the popularity of such arrangements, or has led to new twists being used. The OP has not indicated the residence and citizenship of his family (or his own status for that matter), but if they are all Indian citizens resident in India and are Hindus, then there might be one mechanism for doing what the OP wants to do: apply for a PAN number in the name of the Hindu Undivided Family and use this number to carry out the investments in the name of the Hindu Undivided Family. (There presumably are similar statuses for undivided families for other religions, but I am not familiar with them). There are lots of matters here which are more legal questions than personal finance questions: e.g. if the OP is a US tax resident, then the family presumably will not be able to claim Hindu Undivided Family status since the OP has been divided from the family for tax purposes (or so I think). Even if HUF status is available, the OP might not be able to act as the pater familias while his father is alive, and so on. Consultation with tax lawyers, not just chartered accountants, in India is certainly advisable.\"","title":""},{"docid":"256395","text":"With a question like this you should talk to a tax professional who knows about international tax and knows about both the UK and the country you will be working in. They will give you up to date advice on what can be an extremely complex question. However to get you started I'll tell you what I was told when I did this nearly twenty years ago. It's all about whether you are resident in the UK for tax purposes or not. If you are, you will pay UK tax. If not, you wont (assuming you are being paid outside the UK - check with your professional exactly what is involved). In those days you could be counted as 'non resident' if you spent a complete period of twelve months outside the UK. You can make occasional visits to the UK without invalidating that. Again, check exactly how much you are allowed to return while still being not resident. Usually you will have to pay tax in the country where you are resident, but check the rules there. With some skilful timing you may be able to be considered non-resident in bouth countries, at least for some of the time. Again, your tax professional will know. The bank account question - again get a professional. I don't think it's a problem, but you may have to establish that you are being paid in the foreign country. In general you are going to need an account in the country where you work, so if its a problem get paid there and transfer any money you need in the UK.","title":""},{"docid":"282844","text":"If you have non Residency status in Canada you don't need to file Canadian tax return. To confirm your status you need to contact Canada Revenue (send them letter, probably to complete some form).","title":""},{"docid":"75568","text":"Here's the real reason OKPay (actually the banks they interface with) won't accept US Citizens. The Foreign Account Tax Compliance Act Congress passed the Foreign Account Tax Compliance Act (FATCA) in 2010 without much fanfare. One reason the act was so quiet was its four-year long ramp up; FATCA did not really take effect until 2014. Never before had a single national government attempted, and so far succeeded in, forcing compliance standards on banks across the world. FATCA requires any non-U.S. bank to report accounts held by American citizens worth over $50,000 or else be subject to 30% withholding penalties and possible exclusion from U.S. markets. By mid-2015, more than 100,000 foreign entities had agreed to share financial information with the IRS. Even Russia and China agreed to FATCA. The only major global economy to fight the Feds is Canada; however it was private citizens, not the Canadian government, who filed suit to block FATCA under the International Governmental Agreement clause making it illegal to turn over private bank account information. Read more: The Tax Implications of Opening a Foreign Bank Account | Investopedia http://www.investopedia.com/articles/personal-finance/102915/tax-implications-opening-foreign-bank-account.asp#ixzz4TzEck9Yo Follow us: Investopedia on Facebook","title":""},{"docid":"239030","text":"\"Congrats on the upcoming wedding! Here is the official answer to this question, from the IRS. They note that you can choose to treat your spouse as a US resident for tax purposes and file jointly if you want to, by attaching a certain declaration to your tax return. Though I'm not a tax expert, if your partner has significant income it seems like this might increase your taxes due. You can also apply for an SSN (used for tax filings, joint or separate return) at a social security office or US consulate, by form SS-5, or file form W-7 with the IRS to get a Taxpayer Identification Number which is just as useful for this purpose. Without that, you can write \"\"Non Resident Alien\"\" (or \"\"NRA\"\") in the box for your partner's SSN, and mail in a paper return like that. See IRS Publication 17 page 22 (discussions on TurboTax here, here, etc.).\"","title":""}],"string":"[\n {\n \"docid\": \"518624\",\n \"text\": \"\\\"The other answer has mentioned \\\"\\\"factual resident\\\"\\\", and you have raised the existence of a U.S./Canada tax treaty in your comment, and provided a link to a page about determining residency. I'd like to highlight part of the first link: You are a factual resident of Canada for tax purposes if you keep significant residential ties in Canada while living or travelling outside the country. The term factual resident means that, although you left Canada, you are still considered to be a resident of Canada for income tax purposes. Notes If you have established ties in a country that Canada has a tax treaty with and you are considered to be a resident of that country, but you are otherwise a factual resident of Canada, meaning you maintain significant residential ties with Canada, you may be considered a deemed non-resident of Canada for tax purposes. [...] I'll emphasize that \\\"\\\"considered to be a resident of Canada for income tax purposes\\\"\\\" means you do need to file Canadian income tax returns. The Notes section does indicate the potential treaty exemption that you mentioned, but it is only a potential exemption. Note the emphasis (theirs, not mine) on the word \\\"\\\"may\\\"\\\" in the last paragraph above. Please don't assume \\\"\\\"may\\\"\\\" is necessarily favorable with respect to your situation. The other side of the \\\"\\\"may\\\"\\\" coin is \\\"\\\"may not\\\"\\\". The Determining your residency status page you mentioned in your comment says this: If you want the Canada Revenue Agency's opinion on your residency status, complete either Form NR74, Determination of Residency Status (Entering Canada) or Form NR73, Determination of Residency Status (Leaving Canada), whichever applies, and send it to the International and Ottawa Tax Services Office. To get the most accurate opinion, provide as many details as possible on your form. So, given your ties to Canada, I would suggest that until and unless you have obtained an opinion from the Canada Revenue Agency on your tax status, you would be making a potentially unsafe assumption if you yourself elect not to file your Canadian income tax returns based on your own determination. You could end up liable for penalties and interest if you don't file while you are outside of Canada. Tax residency in Canada is not a simple topic. For instances, let's have a look at S5-F1-C1, Determining an Individual’s Residence Status. It's a long page, but here's one interesting piece: 1.44 The Courts have stated that holders of a United States Permanent Residence Card (otherwise referred to as a Green Card) are considered to be resident in the United States for purposes of paragraph 1 of the Residence article of the Canada-U.S. Tax Convention. For further information, see the Federal Court of Appeal's comments in Allchin v R, 2004 FCA 206, 2004 DTC 6468. [...] ... whereas you are in the U.S. on a TN visa, intended to be temporary. So you wouldn't be exempt just on the basis of your visa and the existence of the treaty. The CRA would look at other circumstances. Consider the \\\"\\\"Centre of vital interests test\\\"\\\": Centre of vital interests test [...] “If the individual has a permanent home in both Contracting States, it is necessary to look at the facts in order to ascertain with which of the two States his personal and economic relations are closer. Thus, regard will be had to his family and social relations, his occupations, his political, cultural or other activities, his place of business, the place from which he administers his property, etc. The circumstances must be examined as a whole, but it is nevertheless obvious that considerations based on the personal acts of the individual must receive special attention. If a person who has a home in one State sets up a second in the other State while retaining the first, the fact that he retains the first in the environment where he has always lived, where he has worked, and where he has his family and possessions, can, together with other elements, go to demonstrate that he has retained his centre of vital interests in the first State.” [emphasis on last sentence is mine] Anyway, I'm acquainted with somebody who left Canada for a few years to work abroad. They assumed that living in the other country for that length of time (>2 years) meant they were non-resident here and so did not have to file. Unfortunately, upon returning to Canada, the CRA deemed them to have been resident all that time based on significant ties maintained, and they subsequently owed many thousands of dollars in back taxes, penalties, and interest. If it were me in a similar situation, I would err on the side of caution and continue to file Canadian income taxes until I got a determination I could count on from the people that make the rules.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"594784\",\n \"text\": \"If you're a US citizen/resident - you pay taxes on your worldwide income regardless of where you live. The logic is that Americans generally don't agree to the view that there's more than one country in the world. If you're non-US person, not physically present in the US, and provide contract work for a US employer - you generally don't pay taxes in the US. The logic is that the US doesn't actually have any jurisdiction over that money, you didn't earn it in the US. That said, your employer might withheld tax and remit it to the IRS, and you'll have to chase them for refund. If you receive income from the US rental property or dividends from a US company - you pay income tax to the US on that income, and then bargain with your home tax authority on refunds of the difference between what you paid in the US and what you should have paid at home. You can also file non-resident tax return in the US to claim what you have paid in excess. The logic is that the money sourced in the US should be taxed in the US. You earned that money in the US. There are additional rules to more specific situation, and there are also bilateral treaties between countries (including a US-Canadian treaty) that supersede national laws. Bottom line, not only that each country has its own laws, there are also different laws for different situations, and if some of the international treaties apply to you - it further complicates the situation. If something is not clear - get a professional advice form a tax accountant licensed in the relevant jurisdictions (in your case - any of the US states, and the Canadian province where you live).\",\n \"title\": \"\"\n },\n {\n \"docid\": \"347186\",\n \"text\": \"Tax liability in US: You would need to determine if you are a resident alien or non resident alien. Resident alien are taxed normally as per US citizens. For the annual remuneration you have quoted it would be in the range of 25%. Refer http://www.moneychimp.com/features/tax_brackets.htm To determine if you are resident alien or non resident alien, you need to be present for certain period in US. There is also an exemption even if you meet this you can still be treated as non resident alien if your tax home is outside US [India in this case] Refer to the link for details to determine your category, the durations are for number of days in financial year, hence it matters when you are in US and the exact durations. http://www.irs.gov/taxtopics/tc851.html Also note that if you are assessed as resident alien, even the income from India will be taxed in US unless you declare there is no income in India. Tax liability in India: The tax liability in India would be depending on your NRI status. This again is tied to the financial year and the number of days you are in country. While the year you are going out of India you need to be away for atleast 183 days for you be considred are NRI. So if you are treated as Indian resident, you would have to pay tax in India on entire income. In the worst case, depending on the period you travel and the dates you travel, you could get classified as citizen in US as well as India and have to pay tax at both places. India and US do not have a dual tax avoidance treaty for individuals. Its there for certain category like small business and certain professions like teacher, research etc.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"272173\",\n \"text\": \"Assuming you are Indian Citizen / Resident for Tax purposes. Your friend in US Citizen / Resident for tax purposes. As you are borrowing these funds and returning, this would NOT be treated as Gift but as Loan. Ensure that you have the right documentation in place. There is no tax when you receive the funds/loan or rebate when you pay back the loan. From India FEMA (Foreign Exchange Management Act) point of view, if you take loan from friends, you cannot by default repatriate funds. You have to take special permission to repatriate the funds out of India.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"570639\",\n \"text\": \"\\\"Transferring the money or keeping it in US does has no effect on taxes. Your residency status has. Assuming you are Resident Alien in US for tax purpose and have paid the taxes to IRS and you are \\\"\\\"Non-Resident\\\"\\\" Indian for tax purposes in India as you are more than 182 outside India. How would it effect my Tax in US and India If you are \\\"\\\"Non-Resident\\\"\\\" in India for tax purposes, there is no tax liability of this in India. I have transferred an amount of approx 15-20k$ to Indian Account (not NRE) By RBI regulation, if you are \\\"\\\"Non-Resident\\\"\\\" then you should get your savings account converted to \\\"\\\"NRO\\\"\\\". You may not may not choose to open an NRE account. To keep the paper work clear it helps that you open an NRE account in India. Any investment needed ? Where do i need to declare if any ? These are not relevant. Note any income generated in India, i.e. interest in Savings account / FDs / Rent etc; taxes need to be paid in India and declared in US and taxes paid in US as well. There is some relief under DTAA. There are quite a few question on this site that will help you clarify what needs to be done.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"575899\",\n \"text\": \"Found a great article (with bibliography) that covers taxation on investment activity by non resident aliens - even covers the special 15% tax on dividends for Canadian residents. It's (dividend tax rate) generally 30% for other NRAs (your 2nd question). And it confirmed my suspicion that there are no capital gains taxes for NRAs. (1st Q) Source: http://invest-faq.com/articles/tax-non-us-nat.html\",\n \"title\": \"\"\n },\n {\n \"docid\": \"352266\",\n \"text\": \"Canada doesn't tax non-residents on income earned/incurred outside of Canada. So, your sister should start with this page to determine the residency status. If she is indeed determined to be non-resident - she should look here to see her obligations. If all she earns she earns outside of Canada - her obligations will be very little, if at all. This is similar to almost any other country in the world, with the notable exception of the United States of America. US citizens are taxed regardless of their residency status, everywhere in the world on worldwide income (unless tax treaty says otherwise).\",\n \"title\": \"\"\n },\n {\n \"docid\": \"214690\",\n \"text\": \"Gifts from your parents are not treated as income for tax purposes. You should not include that in your subsidy calculation. If you are here on a student-visa and have been in the US for less than 5 years, then you are considered a non-resident alien, and you are not required to buy a qualified plan through the insurance marketplace. You might be able to get a cheaper student plan through your school, but the subsidy might be enough that it's still worth it when calculated correctly. If you are a resident-alien or you are a citizen of the US, then you are required to get coverage, though you can choose not to purchase coverage and pay the tax for not having creditable coverage. That tax cannot be collected by the IRS unless you have already had federal tax withheld. They can only confiscate your tax return money to recoup that money. I don't have enough information to recommend one way or the other what you should do, but I would bet that if you recalculated your subsidy without including your parents income it would cover the majority of the cost. You should also consider applying for Medicaid if you meet the eligibility requirements in your state.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"298796\",\n \"text\": \"The finance team from your company should be able to advise you. From what I understand you are Indian Citizen for Tax purposes. Any income you receive globally is taxable in India. In this specific case you are still having a Employee relationship with your employer and as such the place of work does not matter. You are still liable to pay tax in India on the salary. If you are out of India for more than 182 days, you can be considered as Non-Resident from tax point of view. However this clause would not be of any benefit to you as are having a Employee / Employer relationship and being paid in India. Edit: This is only about the India portion of taxes. There maybe a UK protion of it as well, plus legally can you work and your type of Visa in UK may have a bearing on the answer\",\n \"title\": \"\"\n },\n {\n \"docid\": \"228445\",\n \"text\": \"Yes, you have to file a tax return in Canada. Non residents that have earned employment income in Canada are required to file a Canadian personal income tax return. Usually, your employer will have deducted sufficient taxes from your pay-cheques, resulting in a tax refund upon filing your Canadian tax return. You will also receive a tax credit on your US tax return for taxes paid in Canada.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"457455\",\n \"text\": \"It essentially works the same. Some states don't have any income taxes at all (like Florida or Wyoming), some only tax income derived in the state, and some tax worldwide income (like New York or California), similarly to the Federal income taxes. However, if you're living abroad (i.e.: you're a citizen or resident of a foreign country and you live there), you're not considered resident by most of the states (check with your state for specific definitions) for most, if not all, the time of your residency abroad. In such case - you don't pay state taxes, only Federal. You have to remember that foreign income exclusion doesn't apply to the income from your 401k, so you pay the taxes as if you're in the US. You can not use foreign taxes credit as well (but depending on the tax treaty with the country you're moving to, your 401k income might not be taxable there). In some cases you may end up with double taxation: US will tax your 401k income as you're a US citizen and the income is derived from the US sources, and the foreign country will tax the income based on its own laws. This is not a tax advice, and this answer was not intended or written to be used, and it cannot be used by any taxpayer, for the purpose of avoiding penalties that may be imposed on the taxpayer.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"241048\",\n \"text\": \"Taxability depends on your tax residency status. Assuming you are non-resident Indian for tax purposes, then your income is non taxable in India. If you keep the money in Saudi or transfer to India it would be same and non taxable\",\n \"title\": \"\"\n },\n {\n \"docid\": \"360773\",\n \"text\": \"Though non-resident Indians (NRIs) earn their living abroad, their obligation to file tax returns in India doesn't end. With the July 31 deadline for filing returns barely a month away, NRIs need to gear up to file their return if they have income in India that exceeds the basic exemption limit. How to Determine tax residency status: An NRI first needs to determine his tax residency status, that is, whether he falls in the category of resident or non-resident Indian (NRI) for tax purposes. While there may be no ambiguity regarding the status of an NRI who has lived abroad for a long time, those who have moved abroad recently or have returned to India after a long stay abroad need to ascertain their residency status properly.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"475115\",\n \"text\": \"Per the IRS instructions on filing as Head of Household as a Citizen Living Abroad, if you choose to file only your own taxes, and you qualify for Head of Household without them, the IRS does not consider you married: If you are a U.S. citizen married to a nonresident alien you may qualify to use the head of household tax rates. You are considered unmarried for head of household purposes if your spouse was a nonresident alien at any time during the year and you do not choose to treat your nonresident spouse as a resident alien. However, your spouse is not a qualifying person for head of household purposes. You must have another qualifying person and meet the other tests to be eligible to file as a head of household. As such, you could file as Married Filing Separately (if you have no children) or Head of Household (if you have one or more children, a parent, etc. for whom you paid more than half of their upkeep - see the document for more information). You also may choose to file as Married Filing Jointly, if it benefits you to do so (it may, if she earns much less than you). See the IRS document Nonresident Spouse Treated As Resident for more information. If you choose to treat her as a resident, then you must declare her worldwide income. In some circumstances this will be beneficial for you, if you earn substantially more than her and it lowers your tax rate overall to do so. Married Filing Separately severely limits your ability to take some deductions and credits, so it's well worth seeing which is better.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"367562\",\n \"text\": \"I can only answer about the U.S. For question 2, I believe the answer is no. If you are a non-resident alien for tax purposes, then only income connected to the U.S. is reported as income on the tax return. Unless there were any non-deductible contributions to your pre-tax IRAs, when you convert to Roth IRA, the entire amount of the conversion is added to your income. So the tax consequence is the same as if you had that much additional U.S. income. If you are a non-resident alien with no other income in the U.S., then the income you have to report on your U.S. tax return will basically consist of the conversion. Non-resident aliens do not have a standard deduction. However, all people have a personal exemption. If we take 2013 as an example, the exemption is $3900 per person. We will assume that you will file as single or married filing separately (non-resident aliens cannot file as married filing jointly). The first $3900 of income is covered by the exemption, and is not counted in taxable income. For single and MFS, the next $8925 of income is taxed at 10%, then next $27325 of income is taxed at 15%, and so on. So if you convert less than the personal exemption amount every year ($3900 in 2013), then in theory you do not pay any taxes. If you convert a little bit more, then some of the conversion will be taxed at 10%, etc.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"30343\",\n \"text\": \"\\\"You've asked a number of questions. I can answer a few. I've quoted your question before each answer. What are the ins and outs of a foreigner like myself buying rental property in Canada? This is a pretty broad question which can address location, finances, basic suggestions etc. Here's some things to consider: Provincial considerations: Some ins and outs will depend on what province you are considering and what area in that Province. If you plan on owning in Montreal, for example, that's in the province of Quebec and that means you (or someone) will need to be able to operate in the French language. There are other things that might be different from province to province. See stat info below. Canadian vs. US Dollar: Now might be a great time to buy property in Canada since the Canada dollar is weak right now. To give you an idea, at a non-cash rate of 1.2846, a little over $76,000 US will get you over $100k Canadian. That's using the currency converter at rbcroyalbank.com. Taxes for non-resident rental property owners: According to the T4144 Income Tax Guide for Electing Under Section 216 – 2015: \\\"\\\"When you receive rental income from real or immovable property in Canada, the payer, such as the tenant or a property manager, has to withhold non-resident tax at the rate of 25% on the gross rental income paid or credited to you. The payer has to pay us the tax on or before the 15th day of the month following the month the rental income is paid or credited to you.\\\"\\\" If you prefer to send a separate Canadian tax return, you can choose to elect under section 216 of the Income Tax Act. A benefit of this way is that \\\"\\\"electing under section 216 allows you to pay tax on your net Canadian-source rental income instead of on the gross amount. If the non-resident tax withheld by the payer is more than the amount of tax payable calculated on your section 216 return, [they] will refund the excess to you.\\\"\\\" You can find this guide at Canada Revenue's site: http://www.cra-arc.gc.ca/E/pub/tg/t4144/README.html Stats: A good place for stats is the Canada Mortgage and Housing Corporation (CMHC). So, if you are interesting in vacancy rates for example, you can see a table that will show you that the vacancy rate in Ontario is 2.3% and in British Columbia it's 1.5%. However, in New Brunswick it's 8%. The rate for metropolitan areas across Canada is 2.8%. If you want to see or download this table showing the vacancy rates by province and also by metropolitan areas, go to the Canada Mortgage and Housing Corporation site http://www.cmhc.ca/housingmarketinformation/. You can get all sorts of housing information, reports and market information there. I've done well with Condos/Town-homes and would be interested in the same thing over there. Is it pretty much all the same? See the stat site mentioned above to get market info about condos, etc. What are the down payment requirements? For non-owner occupied properties, the down payment is at least 20%. Update in response to comments about being double taxed: Regarding being taxed on income received from the property, if you claim the foreign tax credit you will not be double taxed. According to the IRS, \\\"\\\"The foreign tax credit intends to reduce the double tax burden that would otherwise arise when foreign source income is taxed by both the United States and the foreign country from which the income is derived.\\\"\\\" (from IRS Topic 856 - Foreign Tax Credit) About property taxes: From my understanding, these would not be claimed for the foreign tax credit but can be deducted as business expenses. There are various exceptions and stipulations based on your circumstance, so you need to read Publication 856 - Foreign Tax Credit for Individuals. Here's an excerpt: \\\"\\\"In most cases, only foreign income taxes qualify for the foreign tax credit. Other taxes, such as foreign real and personal property taxes, do not qualify. But you may be able to deduct these other taxes even if you claim the foreign tax credit for foreign income taxes. In most cases, you can deduct these other taxes only if they are expenses incurred in a trade or business or in the production of income. However, you can deduct foreign real property taxes that are not trade or business expenses as an itemized deduction on Schedule A (Form 1040).\\\"\\\" Disclaimers: Sources: IRS Topic 514 Foreign Tax Credit and Publication 856 Foreign Tax Credit for Individuals\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"259602\",\n \"text\": \"I can't give you a specific answer because I'm not a tax accountant, so you should seek advice from a tax professional with experience relevant to your situation. This could be a complicated situation. That being said, one place you could start is the Canada Revenue Agency's statement on investment income, which contains this paragraph: Interest, foreign interest and dividend income, foreign income, foreign non-business income, and certain other income are all amounts you report on your return. They are usually shown on the following slips: T5, T3, T5013, T5013A To avoid double taxation, Canada and the US almost certainly have a foreign tax treaty that ensures you are only taxed in your country of residence. I'm assuming you're a resident of Canada. Also, this page states that: If you received foreign interest or dividend income, you have to report it in Canadian dollars. Use the Bank of Canada exchange rate that was in effect on the day you received the income. If you received the income at different times during the year, use the average annual exchange rate. You should consult a tax professional. I'm not a tax professional, let alone one who specializes in the Canadian tax system. A professional is the only one you should trust to answer your question with 100% accuracy.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"481601\",\n \"text\": \"In theory, when you obtained ownership of your USD cash as a Canadian resident [*resident for tax purposes, which is generally a quicker timeline than being resident for immigration purposes], it is considered to have been obtained by you for the CAD equivalent on that date. For example if you immigrated on Dec 31, 2016 and carried $10k USD with you, when the rate was ~1.35, then Canada deems you to have arrived with $13.5k CAD. If you converted that CAD to USD when the rate was 1.39, you would have received 13.9k CAD, [a gain of $400 to show as income on your tax return]. Receiving the foreign inheritances is a little more complex; those items when received may or may not have been taxable on that day. However whether or not they were taxable, you would calculate a further gain as above, if the fx rate gave you more CAD when you ultimately converted it. If the rate went the other way and you lost CAD-value, you may or may not be able to claim a loss. If it was a small loss, I wouldn't bother trying to claim it due to hassle. If it's a large loss, I would be very sure to research thoroughly before claiming, because something like that probably has a high chance of being audited.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"84528\",\n \"text\": \"\\\"Tax US corporate \\\"\\\"persons (citizens)\\\"\\\" under the same regime as US human persons/citizens, i.e., file/pay taxes on all income earned annually with deductions for foreign taxes paid. Problem solved for both shareholders and governments. [US Citizens and Resident Aliens Abroad - Filing Requirements](https://www.irs.gov/individuals/international-taxpayers/us-citizens-and-resident-aliens-abroad-filing-requirements) >If you are a U.S. citizen or resident alien living or traveling outside the United States, **you generally are required to file income tax returns, estate tax returns, and gift tax returns and pay estimated tax in the same way as those residing in the United States.** Thing is, we know solving this isn't the point. It is to misdirect and talk about everything, but the actual issues, i.e., the discrepancy between tax regimes applied to persons and the massive inequality it creates in tax responsibility. Because that would lead to the simple solutions that the populace need/crave. My guess is most US human persons would LOVE to pay taxes only on what was left AFTER they covered their expenses.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"235266\",\n \"text\": \"In the general case if you have income coming in from a foreign source you need to declare it on your Canadian tax form, and nominally pay tax on it. However Canada has a tax agreement with the UK to ensure that you are not taxed twice. You also declare how much tax you have paid to the UK, and that is deducted from your Canadian tax bill. You may need to consult a tax professional, or maybe just read the Revenue Canada website to get the details. If you are holding this money for a friend, then you may find that this does not count as income to you. If you are getting it transferred to you in Canada, and then immediately passed on to your friend, it probably doesn't count as income (though again a tax professional will probably be helpful). This would mean you don't have to pay Canadian tax. But it's also a bummer because you've paid UK tax, which you might also have avoided, and you can't get that back without a lot of form filling. If this is going to be an ongoing situation, and the amount is significant, then you might look at getting your friend's money (and any you have in a UK account yourself) transferred to an offshore account, where UK tax is not automatically deducted. Most UK banks will do this for non-UK residents.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"288993\",\n \"text\": \"To build a US credit record, you need a Social Security Number (SSN), which is now not available for most non-residents. An alternative is an ITIN number, which is now available to non-residents only if they have US income giving a reason to file a US tax return (do you really want to get into all that...). Assuming you did have a reason to get a ITIN (one reason would be if you sold some ebooks via Amazon US, and need a withholding refund under the tax treaty), then recent reports on Flyertalk give mixed results on whether it's possible to get a credit card with an ITIN, and whether that would build a credit record. It does sound possible in some cases. A credit record in any other country would not help. You would certainly need a US address, and banks are increasingly asking for a physical address, rather than just a mailbox. Regardless, building this history would be of limited benefit to you if you later became a US resident, at that point you would be eligible for a new SSN (different from the ITIN) and have to largely start again. If getting a card is the aim, rather than the credit record, you may find some banks that will offer a secured card (or a debit card), to non-residents, especially in areas with lots of Canadian visitors (border, Florida, Arizona). You'd find it a lot easier with a US address though, and you'd need to shop around a lot of banks in person until you find one with the right rules. Most will simply avoid anyone without an SSN.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"265861\",\n \"text\": \"This answer applies only to corporation tax, not income tax. Different things, income tax is much higher. 12.5% is the low rate for corporation tax. The standard rate is 25%. Or if you're Apple 0%. Like many countries Ireland will only consider you eligible for the low rate of corporation tax if you (your Irish company) can demonstrably prove yourself resident in Ireland. This is more than just address, and you must be able to evidence that your staff work there, your directors are both European Economic Area citizens and have their board meetings in Ireland, and most importantly that they run the company from Ireland, etc. If you're a one man corporation, unless you want to live in Ireland, it's not going to work. Referring to the Irish government's website: The term 'residence' was not, until recently, defined in law. The general rule was that companies, whose 'central management and control' was exercised in the State, were treated as resident here. This rule or test emerged as a result of judicial decisions set down in case law. Factors to be taken into account in establishing where the company's central management and control lie include, for example, where the important questions of company policy are determined, where the majority of directors reside, where the negotiation of major contracts is undertaken and where the company's head office is located. Long story short: An Irish incorporated company is not treated as Irish resident for tax purposes if it is a 'relevant company' ... A Relevant Company is a company that ... is ultimately controlled by persons resident in the EU or in a country with which Ireland has concluded a double taxation treaty\",\n \"title\": \"\"\n },\n {\n \"docid\": \"141458\",\n \"text\": \"\\\"Not really, no. The assumption you're making—withdrawals from a corporation are subject to \\\"\\\"[ordinary] income tax\\\"\\\"—is simplistic. \\\"\\\"Income tax\\\"\\\" encompasses many taxes, some more benign than others, owing to credits and exemptions based on the kind of income. Moreover, the choices you listed as benefits in the sole-proprietor case—the RRSP, the TFSA, and capital gains treatment for non-registered investments—all remain open to the owner of a small corporation ... the RRSP to the extent that the owner has received salary to create contribution room. A corporation can even, at some expense, establish a defined benefit (DB) pension plan and exceed individual RRSP contribution limits. Yes, there is a more tax-efficient way for small business owners to benefit when it comes time to retirement. Here is an outline of two things I'm aware of: If your retirement withdrawals from your Canadian small business corporation would constitute withdrawal from the corporation's retained earnings (profits), i.e. income to the corporation that had already been subject to corporate income tax in prior years, then the corporation is able to declare such distributions as dividends and issue you a T5 slip (Statement of Investment Income) instead of a T4 slip (Statement of Remuneration Paid). Dividends received by Canadian residents from Canadian corporations benefit from the Dividend Tax Credit (DTC), which substantially increases the amount of income you can receive without incurring income tax. See TaxTips.ca - Non-eligible (small business) dividend tax credit (DTC). Quote: For a single individual with no income other than taxable Canadian dividends which are eligible for the small business dividend tax credit, in 2014 approximately $35,551 [...] could be earned before any federal* taxes were payable. * Provincial DTCs vary, and so combined federal/provincial maximums vary. See here. If you're wondering about \\\"\\\"non-eligible\\\"\\\" vs. \\\"\\\"eligible\\\"\\\": private small business corporation dividends are generally considered non-eligible for the best DTC benefit—but they get some benefit—while a large public corporation's dividends would generally be considered eligible. Eligible/non-eligible has to do with the corporation's own income tax rates; since Canadian small businesses already get a big tax break that large companies don't enjoy, the DTC for small businesses isn't as good as the DTC for public company dividends. Finally, even if there is hardly any same-year income tax advantage in taking dividends over salary from an active small business corporation (when you factor in both the income tax paid by the corporation and the individual), dividends still allow a business owner to smooth his income over time, which can result in a lower lifetime average tax rate. So you can use your business as a retained earnings piggy bank to spin off dividends that attract less tax than ordinary income. But! ... if you can convince somebody to buy your business from you, then you can benefit from the lifetime capital gains exemption of up to $800,000 on qualifying small business shares. i.e. you can receive up to $800K tax-free on the sale of your small business shares. This lifetime capital gains exemption is a big carrot—designed, I believe, to incentivize Canadian entrepreneurs to develop going-concern businesses that have value beyond their own time in the business. This means building things that would make your business worth buying, e.g. a valued brand or product, a customer base, intellectual property, etc. Of course, there are details and conditions with all of what I described, and I am not an accountant, so please consult a qualified, conflict-free professional if you need advice specific to your situation.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"102287\",\n \"text\": \"\\\"I'm assuming that by saying \\\"\\\"I'm a US resident now\\\"\\\" you're referring to the residency determination for tax purposes. Should I file a return in the US even though there is no income here ? Yes. US taxes its residents for tax purposes (which is not the same as residents for immigration or other purposes) on worldwide income. If yes, do I get credits for the taxes I paid in India. What form would I need to submit for the same ? I am assuming this form has to be issued by IT Dept in India or the employer in India ? The IRS doesn't require you to submit your Indian tax return with your US tax return, however they may ask for it later if your US tax return comes under examination. Generally, you claim foreign tax credits using form 1116 attached to your tax return. Specifically for India there may also be some clause in the Indo-US tax treaty that might be relevant to you. Treaty claims are made using form 8833 attached to your tax return, and I suggest having a professional (EA/CPA licensed in your State) prepare such a return. Although no stock transactions were done last year, should I still declare the value of total stocks I own ? If so what is an approx. tax rate or the maximum tax rate. Yes, this is done using form 8938 attached to your tax return and also form 114 (FBAR) filed separately with FinCEN. Pay attention: the forms are very similar with regard to the information you provide on them, but they go to different agencies and have different filing requirements and penalties for non-compliance. As to tax rates - that depends on the types of stocks and how you decide to treat them. Generally, the tax rate for PFIC is very high, so that if any of your stocks are classified as PFIC - you'd better talk to a professional tax adviser (EA/CPA licensed in your State) about how to deal with them. Non-PFIC stocks are dealt with the same as if they were in the US, unless you match certain criteria described in the instructions to form 5471 (then a different set of rules apply, talk to a licensed tax adviser). I will be transferring most of my stock to my father this year, will this need to be declared ? Yes, using form 709. Gift tax may be due. Talk to a licensed tax adviser (EA/CPA licensed in your State). I have an apartment in India this year, will this need to be declared or only when I sell the same later on ? If there's no income from it - then no (assuming you own it directly in your own name, for indirect ownership - yes, you do), but when you sell you will have to declare the sale and pay tax on the gains. Again, treaty may come into play, talk to a tax adviser. Also, be aware of Section 121 exclusion which may make it more beneficial for you to sell earlier.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"157712\",\n \"text\": \"I am a US citizen and I want to transfer some amount 10 lakhs+ to my brother from my NRE account in India to his account. My brother is going to purchase something for his business. He is going to return my amount after 3-4 Months From the description it looks like you would like to loan to your brother on repatriation basis. Yes this is allowed. See the RBI Guide here and here for more details. There are some conditions; (iv) Scheme for raising loans from NRIs on repatriation basis Borrowings not exceeding US$ 2,50,000 or its equivalent in foreign exchange by an individual resident in India from his close relatives resident outside India, subject to the conditions that - a) the loan is free of interest; b) the minimum maturity period of the loan is seven years; c) The amount of loan is received by inward remittance in free foreign exchange through normal banking channels or by debit to the NRE/FCNR account of the non-resident lender; d) The loan is utilised for the borrower's personal purposes or for carrying on his normal business activity but not for carrying on agricultural/plantation activities, purchase of immovable property or shares/debentures/bonds issued by companies in India or for re-lending. Although it is mentioned as Seven years, this is revised to one year. Since he cannot deposit into my NRE account I guess he has to deposit it into my NRO account. A repatriate-able loan as above can be deposited into NRE Account. Is there any illegality here doing such transaction? No. Please ensure proper paper work to show this as loan and document the money trail. Also once I get my money in NRO account do I need to pay taxes in India on the money he deposited? This question does not arise.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"14817\",\n \"text\": \"\\\"All the other answers posted thus far discuss matters from the perspective of US tax laws and are unanimous in declaring that what the OP wants to do is indeed a very bad idea. I fully agree: it is a bad idea from the perspective of US tax laws, and is likely a bad idea from the perspective of Indian tax laws too, but what the OP wants to do is (or used to be) common practice in India. In more recent times, India has created a Permanent Account Number (\\\"\\\"PAN number\\\"\\\") for each taxpayer for income tax purposes, and each bank account or investment must have the owner's (or first-named owner's, in case of a joint account) PAN number associated with it. This most likely has decreased the popularity of such arrangements, or has led to new twists being used. The OP has not indicated the residence and citizenship of his family (or his own status for that matter), but if they are all Indian citizens resident in India and are Hindus, then there might be one mechanism for doing what the OP wants to do: apply for a PAN number in the name of the Hindu Undivided Family and use this number to carry out the investments in the name of the Hindu Undivided Family. (There presumably are similar statuses for undivided families for other religions, but I am not familiar with them). There are lots of matters here which are more legal questions than personal finance questions: e.g. if the OP is a US tax resident, then the family presumably will not be able to claim Hindu Undivided Family status since the OP has been divided from the family for tax purposes (or so I think). Even if HUF status is available, the OP might not be able to act as the pater familias while his father is alive, and so on. Consultation with tax lawyers, not just chartered accountants, in India is certainly advisable.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"256395\",\n \"text\": \"With a question like this you should talk to a tax professional who knows about international tax and knows about both the UK and the country you will be working in. They will give you up to date advice on what can be an extremely complex question. However to get you started I'll tell you what I was told when I did this nearly twenty years ago. It's all about whether you are resident in the UK for tax purposes or not. If you are, you will pay UK tax. If not, you wont (assuming you are being paid outside the UK - check with your professional exactly what is involved). In those days you could be counted as 'non resident' if you spent a complete period of twelve months outside the UK. You can make occasional visits to the UK without invalidating that. Again, check exactly how much you are allowed to return while still being not resident. Usually you will have to pay tax in the country where you are resident, but check the rules there. With some skilful timing you may be able to be considered non-resident in bouth countries, at least for some of the time. Again, your tax professional will know. The bank account question - again get a professional. I don't think it's a problem, but you may have to establish that you are being paid in the foreign country. In general you are going to need an account in the country where you work, so if its a problem get paid there and transfer any money you need in the UK.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"282844\",\n \"text\": \"If you have non Residency status in Canada you don't need to file Canadian tax return. To confirm your status you need to contact Canada Revenue (send them letter, probably to complete some form).\",\n \"title\": \"\"\n },\n {\n \"docid\": \"75568\",\n \"text\": \"Here's the real reason OKPay (actually the banks they interface with) won't accept US Citizens. The Foreign Account Tax Compliance Act Congress passed the Foreign Account Tax Compliance Act (FATCA) in 2010 without much fanfare. One reason the act was so quiet was its four-year long ramp up; FATCA did not really take effect until 2014. Never before had a single national government attempted, and so far succeeded in, forcing compliance standards on banks across the world. FATCA requires any non-U.S. bank to report accounts held by American citizens worth over $50,000 or else be subject to 30% withholding penalties and possible exclusion from U.S. markets. By mid-2015, more than 100,000 foreign entities had agreed to share financial information with the IRS. Even Russia and China agreed to FATCA. The only major global economy to fight the Feds is Canada; however it was private citizens, not the Canadian government, who filed suit to block FATCA under the International Governmental Agreement clause making it illegal to turn over private bank account information. Read more: The Tax Implications of Opening a Foreign Bank Account | Investopedia http://www.investopedia.com/articles/personal-finance/102915/tax-implications-opening-foreign-bank-account.asp#ixzz4TzEck9Yo Follow us: Investopedia on Facebook\",\n \"title\": \"\"\n },\n {\n \"docid\": \"239030\",\n \"text\": \"\\\"Congrats on the upcoming wedding! Here is the official answer to this question, from the IRS. They note that you can choose to treat your spouse as a US resident for tax purposes and file jointly if you want to, by attaching a certain declaration to your tax return. Though I'm not a tax expert, if your partner has significant income it seems like this might increase your taxes due. You can also apply for an SSN (used for tax filings, joint or separate return) at a social security office or US consulate, by form SS-5, or file form W-7 with the IRS to get a Taxpayer Identification Number which is just as useful for this purpose. Without that, you can write \\\"\\\"Non Resident Alien\\\"\\\" (or \\\"\\\"NRA\\\"\\\") in the box for your partner's SSN, and mail in a paper return like that. See IRS Publication 17 page 22 (discussions on TurboTax here, here, etc.).\\\"\",\n \"title\": \"\"\n }\n]"}}},{"rowIdx":185,"cells":{"query_id":{"kind":"string","value":"PLAIN-564"},"query":{"kind":"string","value":"angiogenesis"},"positive_passages":{"kind":"list like","value":[{"docid":"MED-4089","text":"Studies have shown an inverse relationship between the consumption of apples and the risk of several cancers. The peels of apple, which have been shown to possess exceptionally high concentrations of antioxidants, are often discarded. In this study, we evaluated the antiproliferative effects of apple peel extract (APE) in variety of cancer cell types. Our data demonstrated that APE, obtained from organic Gala apples, imparted significant reduction in the viability of a variety of cancer cell lines. Further, our data showed a significant decrease in growth and clonogenic survival of human prostate carcinoma CWR22Rnu1 and DU145 cells and breast carcinoma Mcf-7 and Mcf-7:Her18 cells. Also, the antiproliferative effects of APE were found to be accompanied by a G0-G1 phase arrest of prostate and breast cancer cells. Furthermore, APE treatment resulted in a marked concentration-dependent decrease in the protein levels of proliferative cell nuclear antigen, a marker for proliferation. In addition, APE treatment resulted in a marked increase in maspin, a tumor suppressor protein that negatively regulates cell invasion, metastasis, and angiogenesis. Our data suggested that APE possesses strong antiproliferative effects against cancer cells, and apple peels should not be discarded from the diet. Detailed mechanistic studies, especially in appropriate in vivo animal models, are needed to further examine the antiproliferative and preventive effects of APE against cancer.","title":"Antiproliferative effects of apple peel extract against cancer cells."},{"docid":"MED-2572","text":"In traditional cultures, balancing health with a balanced lifestyle was a core belief. The diseases of modern civilization were rare. Indigenous people have patterns of illness very different from Western civilization; yet, they rapidly develop diseases once exposed to Western foods and lifestyles. Food and medicine were interwoven. All cultures used special or functional foods to prevent disease. Food could be used at different times either as food or medicine. Foods, cultivation, and cooking methods maximized community health and well-being. With methods passed down through generations, cooking processes were utilized that enhanced mineral and nutrient bioavailability. This article focuses on what researchers observed about the food traditions of indigenous people, their disease patterns, the use of specific foods, and the environmental factors that affect people who still eat traditional foods.","title":"Traditional non-Western diets."},{"docid":"MED-3549","text":"Studies have shown that fisetin, a small phytochemical molecule, has antitumor activity; however, its antiangiogenic activity has not yet been examined. Accordingly, herein, we investigated the antiangiogenic efficacy and associated mechanisms of fisetin in human umbilical vein endothelial cells (HUVECs). Fisetin (10-50 μM) strongly inhibited the regular serum plus growth supplement- and vascular endothelial growth factor (VEGF)-induced growth (up to 92%, P < 0.001) and survival (up to 16%, P < 0.001) of HUVEC in a dose- and time-dependent manner. Fisetin also caused cell cycle arrest at G(1) (strong) and G(2)/M (moderate) phases together with a decrease in cyclin D1 and an increase in p53 levels. Fisetin-caused cell death was accompanied by decreased expression of survivin and an increase in cleaved levels of caspases-3 and -7 and poly-(ADP-ribose) polymerase along with an increased ratio of Bax to Bcl-2. Furthermore, fisetin inhibited capillary-like tube formation on Matrigel (up to 85%, P < 0.001) as well as migration (up to 66%, P < 0.001), which were associated with decreased expression of endothelial nitric oxide synthase (eNOS) and VEGF in HUVEC. It also decreased the expression of eNOS, VEGF, inducible nitric oxide synthase, matrix metalloproteinase-2 and -9 in A549 and DU145 human cancer cells. In vivo matrigel plug assay in mice showed significant decrease in size (up to 43%, P < 0.001), vascularization and hemoglobin content (up to 94%, P < 0.001) in the plugs from fisetin-treated, compared with control mice. Overall, these results suggest that fisetin inhibits various attributes of angiogenesis, which might contribute to its reported antitumor effects, and therefore, fisetin warrants further investigation for its angiopreventive potential toward cancer control.","title":"Fisetin inhibits various attributes of angiogenesis in vitro and in vivo--implications for angioprevention."},{"docid":"MED-2580","text":"Adequate fruit and vegetable intake was suggested to protect against colorectal cancer and colorectal adenomas; however, several recent prospective studies reported no association. We examined the association between fruits and vegetables and adenomatous polyp recurrence in the Polyp Prevention Trial (PPT). The PPT was a low-fat, high-fiber, high-fruit, and vegetable dietary intervention trial of adenoma recurrence, in which there were no differences in the rate of adenoma recurrence in participants in the intervention and control arms of the trial. In this analysis of the entire PPT trial–based cohort, multiple logistic regression analysis was used to estimate the odds ratio (OR) of advanced and nonadvanced adenoma recurrence within quartiles of baseline and change (baseline minus the mean over 3 y) in fruit and vegetable intake, after adjustment for age, total energyy intake, use of nonsteroidal anti-inflammatory drugs, BMI, and gender. There were no significant associations between nonadvanced adenoma recurrence and overall change in fruit and vegetable consumption; however, those in the highest quartile of change in dry bean intake (greatest increase) compared with those in the lowest had a significantly reduced OR for advanced adenoma recurrence (OR = 0.35; 95% CI, 0.18–0.69; P for trend = 0.001). The median in the highest quartile of change in dry bean intake was 370% higher than the baseline intake. The PPT trial–based cohort provides evidence that dry beans may be inversely associated with advanced adenoma recurrence.","title":"High Dry Bean Intake and Reduced Risk of Advanced Colorectal Adenoma Recurrence among Participants in the Polyp Prevention Trial"},{"docid":"MED-3555","text":"A number of epidemiological studies have investigated associations between various phytochemicals and cancer risk. Phytoestrogens and carotenoids are the two most commonly studied classes of phytochemicals; phytosterols, isothiocyanates, and chlorophyll also have been investigated, although to a much lesser extent. Because there have been no systematic reviews of the literature on all phytochemicals and cancer risk to date, this article systematically reviews 96 published epidemiological studies that examined associations between phytochemicals and cancer risk. Most studies found null associations between individual phytochemicals and cancer risk at various sites. In addition, results from past studies have been largely inconsistent, and observed associations have been of relatively modest magnitude. The most consistent protective effects were observed for higher levels--dietary intake, serum, plasma, or urinary metabolites--of β-carotene and renal cell cancer, β-cryptoxanthin and lung cancer, isothiocyanates and lung cancer, isothiocyanates and gastrointestinal cancer, lignans and postmenopausal breast cancer, and flavonoids and lung cancer. Although elevated risk of certain cancers with higher levels of certain phytochemicals was observed, an insufficient pool of studies examining the same associations or inconsistent findings across studies limit the ability to conclude that any one phytochemical increases cancer risk. Additional research is needed to support previously identified associations in cases where only one study has examined a particular relationship. Importantly, continued research efforts are needed to evaluate the cumulative and interactive effects of numerous phytochemicals and phytochemical-rich foods on cancer risk.","title":"Phytochemicals and cancer risk: a review of the epidemiological evidence."},{"docid":"MED-2577","text":"A case-control study probing the role of diet on the incidence of colorectal cancer was undertaken in Athens, Greece, in a population characterized by ethnic homogeneity but substantial heterogeneity with respect to dietary habits. The case series consisted of 100 consecutive patients with histologically confirmed colorectal cancer admitted to two large hospitals of Athens during a 16-month period; the control series consisted of orthopaedic patients, admitted to the same hospitals during the same time period, individually matched to the index cases by age and sex. Dietary histories concerning the frequency of consumption (per month or per week) of about 80 food items were obtained by the same interviewer. Cases reported significantly less frequent consumption of vegetables (particularly beets, spinach, lettuce and cabbage) and, independently, significantly more frequent consumption of meat (notably lamb and beef). Between the two extremes (high-vegetable, low-meat diet versus high-meat, low-vegetable diet) a risk ratio of about 8 appears to exist, sufficient (in size and direction) to explain a substantial part of the international variation in the incidence of colorectal cancer. Significant associations were not found with beer or other alcoholic beverages, and significant interactions were not noted with respect to age, sex and anatomic localization (colon vs. rectum).","title":"Diet and colorectal cancer: a case-control study in Greece."},{"docid":"MED-2579","text":"There are now extensive scientific data suggesting the potential role of dietary and non-dietary phytochemicals in the prevention and control of prostate cancer (PCA) growth and progression. PCA is a disease of elderly male populations with a relatively slower rate of growth and progression as compared to most other cancers and, therefore, is a candidate disease for preventive intervention. Overall, PCA growth and progression involve aberrant mitogenic and survival signaling and deregulated cell cycle progression, accompanied by gradual accumulation of genetic and epigenetic changes over a period of years. Several mechanisms, including overexpression of growth, survival and angiogenic factors and their receptors, together with a loss/decrease of tumor suppressor p53, retinoblastoma and cyclin-dependent kinase inhibitor, have been implicated in PCA growth and progression. Therefore, phytochemicals targeting these molecular events could have a promising role in PCA prevention and/or therapy. Inositol hexaphosphate (IP6) is a major constituent of most cereals, legumes, nuts, oil seeds and soybean. Taken orally as an over-the-counter dietary/nutrient supplement, and is recognised as offering several health benefits without any known toxicity. In vitro anticancer efficacy of IP6 has been observed in many human, mouse and rat prostate cancer cells. Completed studies also show that oral feeding of IP6 inhibits human PCA xenograft growth in nude mice without toxicity. In a recently completed pilot study, we observed similar preventive effects of IP6 on prostate tumorigenesis in the TRAMP model. Mechanistic studies indicate that IP6 targets mitogenic and survival signaling, as well as cell cycle progression, in PCA cells. IP6 is also shown to target molecular events associated with angiogenesis. Moreover, IP6 has pleiotropic molecular targets for its overall efficacy against PCA and, therefore, could be a suitable candidate agent for preventive intervention of this malignancy in humans.","title":"Prostate cancer and inositol hexaphosphate: efficacy and mechanisms."},{"docid":"MED-2571","text":"Background Prospective, randomized, pilot clinical study was conducted to evaluate the beneficial effects of inositol hexaphosphate (IP6) + Inositol in breast cancer patients treated with adjuvant therapy. Patients and methods Patients with invasive ductal breast cancer where polychemotherapy was indicated were monitored in the period from 2005-2007. Fourteen patients in the same stage of ductal invasive breast cancer were involved in the study, divided in two randomized groups. One group was subjected to take IP6 + Inositol while the other group was taking placebo. In both groups of patients the same laboratory parameters were monitored. When the treatment was finished, all patients have filled questionnaires QLQ C30 and QLQ-BR23 to determine the quality of life. Results Patients receiving chemotherapy, along with IP6 + Inositol did not have cytopenia, drop in leukocyte and platelet counts. Red blood cell counts and tumor markers were unaltered in both groups. However, patients who took IP6 + Inositol had significantly better quality of life (p = 0.05) and functional status (p = 0.0003) and were able to perform their daily activities. Conclusion IP6 + Inositol as an adjunctive therapy is valuable help in ameliorating the side effects and preserving quality of life among the patients treated with chemotherapy.","title":"Efficacy of IP6 + inositol in the treatment of breast cancer patients receiving chemotherapy: prospective, randomized, pilot clinical study"},{"docid":"MED-3552","text":"The study evaluated the protective effects of purple rice (Oryza sativa L.) bran extract (PRE) and its constituents, cyanidin and peonidin, against angiogenesis induced by vascular endothelial growth factor (VEGF). The effects of VEGF and PRE were examined by in vitro tube formation assays and following 14-day co-culture of human umbilical vein endothelial cells (HUVECs) and fibroblasts. The antiangiogenic mechanism of PRE was evaluated by VEGF-induced proliferation and migration of HUVECs and/or human retinal microvascular endothelial cells (HRMECs) and phosphorylation of extracellular signal-regulated kinase (ERK) and p38. The PRE significantly suppressed VEGF-induced tube formation, proliferation and migration in HUVECs and HRMECs as well as phosphorylation of ERK and p38. Cyanidin and peonidin also suppressed the proliferation and migration induced by VEGF. These findings indicate that PRE and anthocyanidins suppress VEGF-induced angiogenesis by inhibiting proliferation and migration and suggest that the inhibition of phosphorylated-ERK and -p38 may be involved in the underlying mechanism. Copyright © 2011 John Wiley & Sons, Ltd.","title":"Purple rice (Oryza sativa L.) extract and its constituents inhibit VEGF-induced angiogenesis."},{"docid":"MED-2570","text":"The functional properties, including antioxidant and chemopreventative capacities as well as the inhibitory effects on angiotensin-converting enzyme (ACE), α-glucosidase and pancreatic lipase, of three Australian-grown faba bean genotypes (Nura, Rossa and TF(Ic*As)*483/13) were investigated using an array of in vitro assays. Chromatograms of on-line post column derivatisation assay coupled with HPLC revealed the existence of active phenolics (hump) in the coloured genotypes, which was lacking in the white-coloured breeding line, TF(Ic*As)*483/13. Roasting reduced the phenolic content, and diminished antioxidant activity by 10-40 % as measured by the reagent-based assays (diphenylpicrylhydrazyl, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) and oxygen radical absorbance capacity) in all genotypes. Cell culture-based antioxidant activity assay (cellular antioxidant activity) showed an increase of activity in the coloured genotypes after roasting. Faba bean extracts demonstrated cellular protection ability against H₂O₂-induced DNA damage (assessed using RAW264.7 cells), and inhibited the proliferation of all human cancer cell lines (BL13, AGS, Hep G2 and HT-29) evaluated. However, the effect of faba bean extracts on the non-transformed human cells (CCD-18Co) was negligible. Flow cytometric analyses showed that faba bean extracts successfully induced apoptosis of HL-60 (acute promyelocytic leukaemia) cells. The faba bean extracts also exhibited ACE, α-glucosidase and pancreatic lipase inhibitory activities. Overall, extracts from Nura (buff-coloured) and Rossa (red-coloured) were comparable, while TF(Ic*As)*483/13 (white-coloured) contained the lowest phenolic content and exhibited the least antioxidant and enzyme inhibition activities. These results are important to promote the utilisation of faba beans in human diets for various health benefits.","title":"In vitro investigations of the potential health benefits of Australian-grown faba beans (Vicia faba L.): chemopreventative capacity and inhibitory ..."},{"docid":"MED-4090","text":"Apple peel is a waste product from dried apple manufacture. The content of phenolic compounds, dietary fiber, and mineral are higher in apple peel, compared to other edible parts of this fruits. The objective of this study was to develop an ingredient from Granny Smith apple peel, using a pilot scale double drum-dryer, as drying technology. The control of all steps to maximize the retention of phenolic compounds and dietary fiber was considered. Operational conditions, such as drying temperature and time were determined, as well as important preprocessing steps like grinding and PPO inhibition. In addition, the physical-chemical characteristics, mineral and sugar content, and technological functional properties such as water retention capacity, solubility index, and dispersability among others, were analyzed. A simple, economical, and suitable pilot scale process, to produce a powder ingredient from apple peel by-product, was obtained. The drying process includes the application of ascorbic acid at 0.5% in the fresh apple peel slurry, drum-dryer operational conditions were 110 degrees C, 0.15 rpm and 0.2 mm drum clearance. The ingredient developed could be considered as a source of phenolic compounds (38.6 mg gallic acid equivalent/g dry base) and dietary fiber (39.7% dry base) in the formulation of foods. Practical Application: A method to develop an ingredient from Granny Smith apple peel using a pilot scale double drum-dryer as drying technology was developed. The method is simple, economical, feasible, and suitable and maximizes the retention of phenolic compounds and dietary fiber present in the raw matter. The ingredient could be used in the formulation of foods.","title":"Development of an ingredient containing apple peel, as a source of polyphenols and dietary fiber."},{"docid":"MED-3548","text":"Cancer metastasis refers to the spread of cancer cells from the primary neoplasm to distant sites, where secondary tumors are formed, and is the major cause of death from cancer. Natural phytochemicals containing phenolic compounds have been widely demonstrated to have the capability to prevent cancer metastasis. Among phenolic compounds, flavonoids are a very large subclass, and they are abundant in food and nutraceuticals. The number of reports demonstrating that flavonoids are an effective natural inhibitor of cancer invasion and metastasis is increasing in the scientific literature. Catechin derivatives, (−)-epigallocatechin-3-gallate, (−)-epigallocatechin, (−)-epicatechin-3-gallate,and (−)-epicatechin, are the most studied compounds in this topic so far; genistein/genistin, silibinin, quercetin, and anthocyanin have also been widely investigated for their inhibitory activities on invasion/metastasis. Other flavonoids in dietary vegetable foods that are responsible for anti-invasive and anti-metastatic activities of tumors include luteolin,apigenin, myricetin, tangeretin, kaempferol, glycitein, licoricidin,daidzein, and naringenin. To effectively overcome the metastatic cascade, including cell-cell attachment, tissue barrier degradation, migration, invasion, cell-matrix adhesion,and angiogenesis, it is essential that a bioactive compound prevent tumor cells from metastasizing. This review summarizes the effects of flavonoids on the metastatic cascade and the related proteins, the in vitro anti-invasive activity of flavonoids against cancer cells, and the effects of flavonoids on antiangiogenic and in vivo anti-metastatic models. The available scientific evidence indicates that flavonoids are a ubiquitous dietary phenolics subclass and exert extensive in vitro anti-invasive and in vivo anti-metastatic activities.","title":"Flavonoids, a ubiquitous dietary phenolic subclass, exert extensive in vitro anti-invasive and in vivo anti-metastatic activities."},{"docid":"MED-2574","text":"Inositol hexaphosphate (IP(6)) is a naturally occurring polyphosphorylated carbohydrate, abundantly present in many plant sources and in certain high-fiber diets, such as cereals and legumes. In addition to being found in plants, IP(6) is contained in almost all mammalian cells, although in much smaller amounts, where it is important in regulating vital cellular functions such as signal transduction, cell proliferation, and differentiation. For a long time IP(6) has been recognized as a natural antioxidant. Recently IP(6) has received much attention for its role in cancer prevention and control of experimental tumor growth, progression, and metastasis. In addition, IP(6) possesses other significant benefits for human health, such as the ability to enhance immune system, prevent pathological calcification and kidney stone formation, lower elevated serum cholesterol, and reduce pathological platelet activity. In this review we show the efficacy and discuss some of the molecular mechanisms that govern the action of this dietary agent. Exogenously administered IP(6) is rapidly taken up into cells and dephosphorylated to lower inositol phosphates, which further affect signal transduction pathways resulting in cell cycle arrest. A striking anticancer action of IP(6) was demonstrated in different experimental models. In addition to reducing cell proliferation, IP(6) also induces differentiation of malignant cells. Enhanced immunity and antioxidant properties also contribute to tumor cell destruction. Preliminary studies in humans show that IP(6) and inositol, the precursor molecule of IP(6), appear to enhance the anticancer effect of conventional chemotherapy, control cancer metastases, and improve quality of life. Because it is abundantly present in regular diet, efficiently absorbed from the gastrointestinal tract, and safe, IP(6) + inositol holds great promise in our strategies for cancer prevention and therapy. There is clearly enough evidence to justify the initiation of full-scale clinical trials in humans.","title":"Protection against cancer by dietary IP6 and inositol."},{"docid":"MED-3553","text":"Several epidemiological studies have indicated that abundant consumption of foods from plant origin is associated with a reduced risk of developing several types of cancers. This chemopreventive effect is related to the high content of these foods in phytochemicals, such as polyphenols, that interfere with several processes involved in cancer progression including tumor cell growth, survival and angiogenesis. In addition to the low intake of plant-based foods, increased body mass and physical inactivity have recently emerged as other important lifestyle factors influencing cancer risk, leading to the generation of low-grade chronic inflammatory conditions which are a key process involved in tumor progression. The objectives of the current study are to investigate the inhibitory effects of these polyphenols on angiogenesis triggered by an inflammatory cytokine (IL-6) and to determine the mechanisms underlying this action. We found that, among the tested polyphenols, apigenin and luteolin were the most potent angiogenesis inhibitors through their inhibitory effect on the inflammatory cytokine IL-6/STAT3 pathway. These effects resulted in modulation of the activation of extracellular signal-regulated kinase-1/2 signaling triggered by IL-6, as well as in a marked reduction in the proliferation, migration and morphogenic differentiation of endothelial cells. Interestingly, these polyphenols also modulated the expression of IL-6 signal transducing receptor (IL-6Rα) and the secretion of the extracellular matrix degrading enzyme MMP-2 as well as the expression of suppressor of cytokine signaling (SOCS3) protein. Overall, these results may provide important new information on the role of diet in cancer prevention. Copyright © 2012 Elsevier Inc. All rights reserved.","title":"Diet-derived polyphenols inhibit angiogenesis by modulating the interleukin-6/STAT3 pathway."},{"docid":"MED-2583","text":"Inositol hexaphosphate (IP(6)), a naturally polyphosphorylated carbohydrate, has been reported to have significant in vivo and in vitro anticancer activity against numerous tumours, such as colon, prostate, breast, liver and rhabdomyosarcomas. To confirm this activity in haematological malignancies and to characterize some of the mechanisms of IP(6) action, we analysed its effects on human leukaemic cell lines and fresh chronic myelogenous leukaemia (CML) progenitor cells using a combined cellular and molecular approach. IP(6) had a dose-dependent cytotoxic effect on all of the evaluated cell lines, with accumulation in the G2M phase in two out of five cell lines tested. At the molecular level, cDNA microarray analysis after IP(6) exposure showed an extensive downmodulation of genes involved in transcription and cell cycle regulation and a coherent upregulation of cell cycle inhibitors. Furthermore, IP(6) treatment of fresh leukaemic samples of bone marrow CD34+ CML progenitor cells significantly inhibited granulocyte-macrophage colony-forming unit (CFU-GM) formation (P = 0.0062) in comparison to normal bone marrow specimens, which were not affected. No differentiating effect on HL60 cells was observed. Taken together, our results confirm the antiproliferative activity of IP(6) and suggest that it may have a specific antitumour effect also in chronic myeloid leukaemias, via active gene modulation.","title":"Effect of inositol hexaphosphate (IP(6)) on human normal and leukaemic haematopoietic cells."},{"docid":"MED-2584","text":"In a 6-year prospective study, the authors examined the relation between diet and incident colon cancer among 32,051 non-Hispanic white cohort members of the Adventist Health Study (California, 1976-1982) who, at baseline, had no documented or reported history of cancer. The risk of colon cancer was determined from proportional hazards regression with adjustment for age and other covariates. The authors found a positive association with total meat intake (risk ratio (RR) for > or =1 time/week vs. no meat intake = 1.85, 95% confidence interval (CI) 1.19-2.87; p for trend = 0.01) and, among subjects who favored specific types of meat, positive associations with red meat intake (RR for > or =1 time/week vs. no red meat intake = 1.90, 95% CI 1.16-3.11; p for trend = 0.02) and white meat intake (RR for > or =1 time/week vs. no white meat intake = 3.29, 95% CI 1.60-6.75; p for trend = 0.006). An inverse association with legume intake (RR for >2 times/week vs. <1 time/week = 0.53, 95% CI 0.33-0.86; p for trend = 0.03) was observed. Among men, a positive association with body mass index was observed (relative to the RR for tertile III (>25.6 kg/m2) vs. tertile I (<22.5 kg/m2) = 2.63, 95% CI 1.12-6.13; p for trend = 0.05). A complex relation was identified whereby subjects exhibiting a high red meat intake, a low legume intake, and a high body mass experienced a more than threefold elevation in risk relative to all other patterns based on these variables. This pattern of putative risk factors would likely contribute to increases in both insulin resistance (high body mass, high red meat intake) and glycemic load (low legume intake), a synergism that, if causal, implicates hyperinsulinemic exposure in colon carcinogenesis. The overall findings from this cohort identify both red meat intake and white meat intake as important dietary risk factors for colon cancer and raise the possibility that the risk due to red meat intake reflects a more complex etiology.","title":"Dietary risk factors for colon cancer in a low-risk population."},{"docid":"MED-4465","text":"Adult stem cells of the mammary gland (MaSCs) are a highly dynamic population of cells that are responsible for the generation of the gland during puberty and its expansion during pregnancy. In recent years significant advances have been made in understanding how these cells are regulated during these developmentally important processes both in humans and in mice. Understanding how MaSCs are regulated is becoming a particularly important area of research, given that they may be particularly susceptible targets for transformation in breast cancer. Here, we summarize the identification of MaSCs, how they are regulated and the evidence for their serving as the origins of breast cancer. In particular, we focus on how changes in MaSC populations may explain both the increased risk of developing aggressive ER/PR(−) breast cancer shortly after pregnancy and the long-term decreased risk of developing ER/PR(+) tumors.","title":"From milk to malignancy: the role of mammary stem cells in development, pregnancy and breast cancer"},{"docid":"MED-4464","text":"Over the last decade, the notion that tumors are maintained by their own stem cells, the so-called cancer stem cells, has created great excitement in the research community. This review attempts to summarize the underlying concepts of this notion, to distinguish hard facts from beliefs and to define the future challenges of the field.","title":"The cancer stem cell: premises, promises and challenges."},{"docid":"MED-2559","text":"Inositol hexaphosphate (IP6) has anti-cancer properties, but recently other extracellular functions have been observed for IP6, including enhancing superoxide production and phagocytosis by neutrophils in the presence of microbial stimuli. This study investigated other inflammatory functions of IP6 on adherent neutrophils. The effect of IP6 on the release of IL-8, tumour necrosis factor (TNF-alpha) and IL-6 by neutrophils attached to either plastic or laminin for up to 6 hours in response to stimulation with lipopolysaccharide or N-formyl-Met-Leu-Phe (fMLP) was investigated. An increase in IL-8 secretion by stimulated cells occurred in the presence of IP6. The incubation of cells attached to laminin with IP6 alone (100-250 BM) did not effect cell morphology, but in the presence of 10(-7) M fMLP altered cell shape. A direct effect of IP6 on cell function was to trigger a sustained assembly of F-actin. Thus, exposure of neutrophils to low levels of IP6 appears to modulate selective neutrophil functions.","title":"Effect of IP6 on human neutrophil cytokine production and cell morphology."},{"docid":"MED-3554","text":"A great deal of effort is now being devoted to the development of new drugs that hopefully will control the spread of inoperable cancer by safely inhibiting tumor-evoked angiogenesis. However, there is growing evidence that certain practical nutritional measures have the potential to slow tumor angiogenesis, and it is reasonable to anticipate that, by combining several measures that work in distinct but complementary ways to impede the angiogenic process, a clinically useful 'multifocal angiostatic therapy' (MAT) might be devised. Several measures which might reasonably be included in such a protocol are discussed below, and include: a low-fat, low-glycemic index vegan diet, which may down-regulate the systemic IGF-I activity that supports angiogenesis; supplemental omega-3-rich fish oil, which has been shown to inhibit endothelial expression of Flk-1, a functionally crucial receptor for VEGF, and also can suppress tumor production of pro-angiogenic eicosanoids; high-dose selenium, which has recently been shown to inhibit tumor production of VEGF; green tea polyphenols, which can suppress endothelial responsiveness to both VEGF and fibroblast growth factor; and high-dose glycine, whose recently reported angiostatic activity may reflect inhibition of endothelial cell mitosis, possibly mediated by activation of glycine-gated chloride channels. In light of evidence that tumor-evoked angiogenesis has a high requirement for copper, copper depletion may have exceptional potential as an angiostatic measure, and is most efficiently achieved with the copper-chelating drug tetrathiomolybdate. If logistical difficulties make it difficult to acquire this experimental drug, high-dose zinc supplementation can achieve a slower depletion of the body's copper pool, and in any case can be used as maintenance therapy to maintain an adequate level of copper depletion. A provisional protocol is offered for a nutritionally based MAT entailing a vegan diet and supplemental intakes of fish oil, selenium, green tea polyphenols, glycine, and zinc. Inasmuch as cox-2 is overexpressed in many cancers, and cAMP can boost tumor production of various angiogenic factors as well as autogenous growth factors, adjunctive use of cox-2-specific NSAIDS may be warranted in some cases.","title":"A wholly nutritional 'multifocal angiostatic therapy' for control of disseminated cancer."},{"docid":"MED-4319","text":"The article gives an overview of phytic acid in food and of its significance for human nutrition. It summarises phytate sources in foods and discusses problems of phytic acid/phytate contents of food tables. Data on phytic acid intake are evaluated and daily phytic acid intake depending on food habits is assessed. Degradation of phytate during gastro-intestinal passage is summarised, the mechanism of phytate interacting with minerals and trace elements in the gastro-intestinal chyme described and the pathway of inositol phosphate hydrolysis in the gut presented. The present knowledge of phytate absorption is summarised and discussed. Effects of phytate on mineral and trace element bioavailability are reported and phytate degradation during processing and storage is described. Beneficial activities of dietary phytate such as its effects on calcification and kidney stone formation and on lowering blood glucose and lipids are reported. The antioxidative property of phytic acid and its potentional anticancerogenic activities are briefly surveyed. Development of the analysis of phytic acid and other inositol phosphates is described, problems of inositol phosphate determination and detection discussed and the need for standardisation of phytic acid analysis in foods argued.","title":"Phytate in foods and significance for humans: food sources, intake, processing, bioavailability, protective role and analysis."},{"docid":"MED-2568","text":"Inositol hexaphosphate (InsP6 or IP6) is ubiquitous. At 10 microM to 1 mM concentrations, IP6 and its lower phosphorylated forms (IP(1-5)) as well as inositol (Ins) are contained in most mammalian cells, wherein they are important in regulating vital cellular functions such as signal transduction, cell proliferation and differentiation. A striking anti-cancer action of IP6 has been demonstrated both in vivo and in vitro, which is based on the hypotheses that exogenously administered IP6 may be internalized, dephosphorylated to IP(1-5), and inhibit cell growth. There is additional evidence that Ins alone may further enhance the anti-cancer effect of IP6. Besides decreasing cellular proliferation, IP6 also causes differentiation of malignant cells often resulting in a reversion to normal phenotype. These data strongly point towards the involvement of signal transduction pathways, cell cycle regulatory genes, differentiation genes, oncogenes and perhaps, tumor suppressor genes in bringing about the observed anti-neoplastic action of IP6.","title":"IP6: a novel anti-cancer agent."},{"docid":"MED-2573","text":"A significant anticancer activity of the naturally occurring carbohydrate inositol hexaphosphate (IP(6)) has been reported against numerous cancer models. Since tumors require angiogenesis for growth and metastasis, we hypothesize that IP(6) reduces tumor growth by inhibiting angiogenesis. Because angiogenesis depends on the interaction between endothelial and tumor cells, we investigated the effect of IP(6) on both. IP(6) inhibited the proliferation and induced the differentiation of endothelial cells in vitro; the growth of bovine aortic endothelial cells (BAECs) evaluated by MTT proliferation assay was inhibited in a dose-dependent manner (IC(50) = 0.74 mM). The combination of IP(6) and vasostatin, a calreticulin fragment with anti-angiogenic activity, was synergistically superior in growth inhibition than either compound. IP(6) inhibited human umbilical vein endothelial cell (HUVEC) tube formation (in vitro capillary differentiation) on a reconstituted extracellular matrix, Matrigel, and disrupted pre-formed tubes. IP(6) significantly reduced basic fibroblast growth factor (bFGF)-induced vessel formation (P < 0.01) in vivo in Matrigel plug assay. Exposure of HepG2, a human hepatoma cell line, to IP(6) for 8 h, resulted in a dose-dependent decrease in the mRNA levels of vascular endothelial growth factor (VEGF), as assessed by RT-PCR. IP(6) treatment of HepG2 cells for 24 h also significantly reduced the VEGF protein levels in conditioned medium, in a concentration-dependent manner (P = 0.012). Thus, IP(6) has an inhibitory effect on induced angiogenesis.","title":"Anti-angiogenic activity of inositol hexaphosphate (IP6)."},{"docid":"MED-3550","text":"Between 2000 and 2050, the number of new cancer patients diagnosed annually is expected to double, with an accompanying increase in treatment costs of more than $80 billion over just the next decade. Efficacious strategies for cancer prevention will therefore be vital for improving patients' quality of life and reducing healthcare costs. Judah Folkman first proposed antiangiogenesis as a strategy for preventing dormant microtumors from progressing to invasive cancer. Although antiangiogenic drugs are now available for many advanced malignancies (colorectal, lung, breast, kidney, liver, brain, thyroid, neuroendocrine, multiple myeloma, myelodysplastic syndrome), cost and toxicity considerations preclude their broad use for cancer prevention. Potent antiangiogenic molecules have now been identified in dietary sources, suggesting that a rationally designed antiangiogenic diet could provide a safe, widely available, and novel strategy for preventing cancer. This paper presents the scientific, epidemiologic, and clinical evidence supporting the role of an antiangiogenic diet for cancer prevention.","title":"Tumor Angiogenesis as a Target for Dietary Cancer Prevention"},{"docid":"MED-2575","text":"Introduction Matrix metalloproteinases (MMPs) have repeatedly been shown to play a very active role in extracellular matrix degradation associated with tumor invasion and metastasis. Tissue inhibitors of MMPs (TIMPs) are well-known for their ability to inhibit MMP activity thereby inhibiting malignant progression. Inositol hexaphosphate (IP6 phytic acid) has been recognized to have both preventive and therapeutic effects against various cancers including that of colon. In in vitro studies, IP6 has been demonstrated to inhibit cancer cell adhesion and migration. In the present study, the effect of IP6 on the expression of MMP and TIMP genes was evaluated in unstimulated and IL-1β-stimulated colon cancer cell line Caco-2. Materials and methods Real-time QRT-PCR was used to validate the transcription level of selected MMP and TIMP genes in Caco-2 cells after treatment with 1 ng/ml of IL-1β, 2.5 mM of IP6, and both for 6, 12, and 24 h. Results Stimulation of cells with IL-1β only resulted in an overexpression of MMP and their TIMP mRNAs. A significant decrease in MMP-13, MMP-3, MMP-2, and TIMP-1 basal expression was achieved by IP6. IP6 was also an efficient downregulator of MMP-1, MMP-9, and TIMP-2 genes transcription stimulated by IL-1β in 6 h lasting culture. After 12 h, IL-1β-induced MMP-2 mRNA expression was significantly reduced by IP6. Conclusion Proinflammatory cytokine IL-1β upregulates MMP and TIMP mRNAs expression in colon cancer epithelial cells Caco-2. IP6 (2.5 mM) influences constitutive expression of both MMP and TIMP genes and downregulates IL-1β stimulated transcription of some of these genes. IP6 exerts its anti-metastatic activity through modulation of MMP and TIMP genes expression to prevent cancer cell migration and invasion.","title":"The effect of inositol hexaphosphate on the expression of selected metalloproteinases and their tissue inhibitors in IL-1β-stimulated colon cancer cells"},{"docid":"MED-2581","text":"A hospital-based case-control study of diet and colorectal cancer was conducted among Chinese in Singapore (who constitute 77% of the population). A total of 203 cases and 425 controls were included. A history of the usual dietary intake one year prior to interview was taken using a quantitative food frequency questionnaire. Daily intakes of nutrients and selected food items were computed and stratified by tertiles of the control range, to assess risk in low-, medium- and high-intake categories. Effects were adjusted in analysis for age, sex, Chinese dialect group and occupation. For cancers of colon and rectum combined, significant observations were a protective effect of high cruciferous vegetable intake (OR = 0.50, p less than 0.01) and a predisposing effect of a high meat/vegetable consumption ratio (OR = 1.77, p less than 0.05). Similar results were observed for colon cancer alone. For rectal cancer alone (only 71 cases), significant (p less than 0.05) protective effects were observed for high intakes of protein (OR = 0.61), fibre (OR = 0.46), beta-carotene (OR = 0.54), cruciferous vegetables (OR = 0.51) and total vegetables (OR = 0.51). When further assessed by multiple logistic regression, tests for trend and assessment of risk in the extreme highest and lowest quintiles of the control range, the factors consistently significant were cruciferous vegetable intake and the meat/vegetable ratio. A particularly high relative risk was also noted in association with low coffee consumption (OR = 1.59, with p less than 0.05 for trend). No consistent trends were noted for fat or fibre intakes. For non-dietary variables investigated, a history of cholecystectomy increased the risk of both cancers combined (OR = 3.43, p less than 0.05) and colon cancer alone (OR = 4.39, p less than 0.01). This study in an Asian population of countries of Southern and Eastern Asia newly undergoing industrialization and in which rapid economic change is reflected in changing cancer patterns, suggests that the protective effects of certain dietary constituents, notably the cruciferous vegetables, may be more important than the hitherto stressed carcinogenic potential of fat and protein.","title":"Colorectal cancer and diet in an Asian population--a case-control study among Singapore Chinese."},{"docid":"MED-3551","text":"Breast cancer is the leading cause of cancer-related deaths for women in the United States and the rest of the world. About 8% of women develop breast cancer during the course of their lives. Dietary habits are closely associated with both the risk and progression of breast cancer. Dietary agents have accumulated increasing importance with regards to the prevention and treatment of breast cancer. One such manner by which these compounds can target breast cancer development and progression is through interference with the angiogenic pathways. Angiogenesis is an intricate process that involves the development of new capillaries from previously existing blood vessels. Disruption of this pathway, therefore, provides a novel and effective avenue for therapeutic intervention of breast cancer. Various phytochemicals found in the diet kill breast cancer cells in vitro and prevent as well as suppress breast cancer progression in various preclinical animal models. This review examines the value of dietary phytoconstituents in the prevention and treatment of breast cancer through modulation of the intricate and complex process of angiogenesis. In addition, the potential benefits, challenges, and future directions of research on anti-angiogenic dietary phytochemicals in the prevention and intervention of breast cancer are also addressed. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.","title":"Modulation of angiogenesis by dietary phytoconstituents in the prevention and intervention of breast cancer."},{"docid":"MED-2578","text":"The incidence of colonic cancer differs widely between various human populations. It has been suggested that dietary fiber content is of utmost importance and is inversely related to the occurrence of colonic cancer. However, high-fiber diets are not always correlated with low frequency of colonic cancer, suggesting the involvement of additional dietary constituents. Inositol hexaphosphate (phytic acid) is an abundant plant seed component present in many, but not all, fiber-rich diets. The authors have found that phytic acid is a potent inhibitor of iron-mediated generation of the hazardous oxidant, hydroxyl radical. Herein, the authors propose that inhibition of intracolonic hydroxyl radical generation, via the chelation of reactive iron by phytic acid, may help explain the suppression of colonic carcinogenesis and other inflammatory bowel diseases by diets rich in phytic acid.","title":"Dietary suppression of colonic cancer. Fiber or phytate?"},{"docid":"MED-2988","text":"This review describes the present state of knowledge about phytic acid (phytate), which is often present in legume seeds. The antinutritional effects of phytic acid primarily relate to the strong chelating associated with its six reactive phosphate groups. Its ability to complex with proteins and particularly with minerals has been a subject of investigation from chemical and nutritional viewpoints. The hydrolysis of phytate into inositol and phosphates or phosphoric acid occurs as a result of phytase or nonenzymatic cleavage. Enzymes capable of hydrolysing phytates are widely distributed in micro-organisms, plants and animals. Phytases act in a stepwise manner to catalyse the hydrolysis of phytic acid. To reduce or eliminate the chelating ability of phytate, dephosphorylation of hexa- and penta-phosphate forms is essential since a high degree of phosphorylation is necessary to bind minerals. There are several methods of decreasing the inhibitory effect of phytic acid on mineral absorption (cooking, germination, fermentation, soaking, autolysis). Nevertheless, inositol hexaphosphate is receiving increased attention owing to its role in cancer prevention and/or therapy and its hypocholesterolaemic effect.","title":"The role of phytic acid in legumes: antinutrient or beneficial function?"},{"docid":"MED-2585","text":"Inositol hexaphosphate (IP6) is a naturally occurring polyphosphorylated carbohydrate that is present in substantial amounts in almost all plant and mammalian cells. It was recently recognized to possess multiple biological functions. A striking anticancer effect of IP6 was demonstrated in different experimental models. Inositol is also a natural constituent possessing moderate anticancer activity. The most consistent and best anticancer results were obtained from the combination of IP6 plus inositol. In addition to reducing cell proliferation, IP6 increases differentiation of malignant cells, often resulting in a reversion to normal phenotype. Exogenously administered IP6 is rapidly taken into the cells and dephosphorylated to lower-phosphate inositol phosphates, which further interfere with signal transduction pathways and cell cycle arrest. Enhanced immunity and antioxidant properties can also contribute to tumor cell destruction. However, the molecular mechanisms underlying this anticancer action are not fully understood. Because it is abundantly present in regular diet, efficiently absorbed from the gastrointestinal tract, and safe, IP6 holds great promise in our strategies for the prevention and treatment of cancer. IP6 plus inositol enhances the anticancer effect of conventional chemotherapy, controls cancer metastases, and improves the quality of life, as shown in a pilot clinical trial. The data strongly argue for the use of IP6 plus inositol in our strategies for cancer prevention and treatment. However, the effectiveness and safety of IP6 plus inositol at therapeutic doses needs to be determined in phase I and phase II clinical trials in humans.","title":"Cancer inhibition by inositol hexaphosphate (IP6) and inositol: from laboratory to clinic."}],"string":"[\n {\n \"docid\": \"MED-4089\",\n \"text\": \"Studies have shown an inverse relationship between the consumption of apples and the risk of several cancers. The peels of apple, which have been shown to possess exceptionally high concentrations of antioxidants, are often discarded. In this study, we evaluated the antiproliferative effects of apple peel extract (APE) in variety of cancer cell types. Our data demonstrated that APE, obtained from organic Gala apples, imparted significant reduction in the viability of a variety of cancer cell lines. Further, our data showed a significant decrease in growth and clonogenic survival of human prostate carcinoma CWR22Rnu1 and DU145 cells and breast carcinoma Mcf-7 and Mcf-7:Her18 cells. Also, the antiproliferative effects of APE were found to be accompanied by a G0-G1 phase arrest of prostate and breast cancer cells. Furthermore, APE treatment resulted in a marked concentration-dependent decrease in the protein levels of proliferative cell nuclear antigen, a marker for proliferation. In addition, APE treatment resulted in a marked increase in maspin, a tumor suppressor protein that negatively regulates cell invasion, metastasis, and angiogenesis. Our data suggested that APE possesses strong antiproliferative effects against cancer cells, and apple peels should not be discarded from the diet. Detailed mechanistic studies, especially in appropriate in vivo animal models, are needed to further examine the antiproliferative and preventive effects of APE against cancer.\",\n \"title\": \"Antiproliferative effects of apple peel extract against cancer cells.\"\n },\n {\n \"docid\": \"MED-2572\",\n \"text\": \"In traditional cultures, balancing health with a balanced lifestyle was a core belief. The diseases of modern civilization were rare. Indigenous people have patterns of illness very different from Western civilization; yet, they rapidly develop diseases once exposed to Western foods and lifestyles. Food and medicine were interwoven. All cultures used special or functional foods to prevent disease. Food could be used at different times either as food or medicine. Foods, cultivation, and cooking methods maximized community health and well-being. With methods passed down through generations, cooking processes were utilized that enhanced mineral and nutrient bioavailability. This article focuses on what researchers observed about the food traditions of indigenous people, their disease patterns, the use of specific foods, and the environmental factors that affect people who still eat traditional foods.\",\n \"title\": \"Traditional non-Western diets.\"\n },\n {\n \"docid\": \"MED-3549\",\n \"text\": \"Studies have shown that fisetin, a small phytochemical molecule, has antitumor activity; however, its antiangiogenic activity has not yet been examined. Accordingly, herein, we investigated the antiangiogenic efficacy and associated mechanisms of fisetin in human umbilical vein endothelial cells (HUVECs). Fisetin (10-50 μM) strongly inhibited the regular serum plus growth supplement- and vascular endothelial growth factor (VEGF)-induced growth (up to 92%, P < 0.001) and survival (up to 16%, P < 0.001) of HUVEC in a dose- and time-dependent manner. Fisetin also caused cell cycle arrest at G(1) (strong) and G(2)/M (moderate) phases together with a decrease in cyclin D1 and an increase in p53 levels. Fisetin-caused cell death was accompanied by decreased expression of survivin and an increase in cleaved levels of caspases-3 and -7 and poly-(ADP-ribose) polymerase along with an increased ratio of Bax to Bcl-2. Furthermore, fisetin inhibited capillary-like tube formation on Matrigel (up to 85%, P < 0.001) as well as migration (up to 66%, P < 0.001), which were associated with decreased expression of endothelial nitric oxide synthase (eNOS) and VEGF in HUVEC. It also decreased the expression of eNOS, VEGF, inducible nitric oxide synthase, matrix metalloproteinase-2 and -9 in A549 and DU145 human cancer cells. In vivo matrigel plug assay in mice showed significant decrease in size (up to 43%, P < 0.001), vascularization and hemoglobin content (up to 94%, P < 0.001) in the plugs from fisetin-treated, compared with control mice. Overall, these results suggest that fisetin inhibits various attributes of angiogenesis, which might contribute to its reported antitumor effects, and therefore, fisetin warrants further investigation for its angiopreventive potential toward cancer control.\",\n \"title\": \"Fisetin inhibits various attributes of angiogenesis in vitro and in vivo--implications for angioprevention.\"\n },\n {\n \"docid\": \"MED-2580\",\n \"text\": \"Adequate fruit and vegetable intake was suggested to protect against colorectal cancer and colorectal adenomas; however, several recent prospective studies reported no association. We examined the association between fruits and vegetables and adenomatous polyp recurrence in the Polyp Prevention Trial (PPT). The PPT was a low-fat, high-fiber, high-fruit, and vegetable dietary intervention trial of adenoma recurrence, in which there were no differences in the rate of adenoma recurrence in participants in the intervention and control arms of the trial. In this analysis of the entire PPT trial–based cohort, multiple logistic regression analysis was used to estimate the odds ratio (OR) of advanced and nonadvanced adenoma recurrence within quartiles of baseline and change (baseline minus the mean over 3 y) in fruit and vegetable intake, after adjustment for age, total energyy intake, use of nonsteroidal anti-inflammatory drugs, BMI, and gender. There were no significant associations between nonadvanced adenoma recurrence and overall change in fruit and vegetable consumption; however, those in the highest quartile of change in dry bean intake (greatest increase) compared with those in the lowest had a significantly reduced OR for advanced adenoma recurrence (OR = 0.35; 95% CI, 0.18–0.69; P for trend = 0.001). The median in the highest quartile of change in dry bean intake was 370% higher than the baseline intake. The PPT trial–based cohort provides evidence that dry beans may be inversely associated with advanced adenoma recurrence.\",\n \"title\": \"High Dry Bean Intake and Reduced Risk of Advanced Colorectal Adenoma Recurrence among Participants in the Polyp Prevention Trial\"\n },\n {\n \"docid\": \"MED-3555\",\n \"text\": \"A number of epidemiological studies have investigated associations between various phytochemicals and cancer risk. Phytoestrogens and carotenoids are the two most commonly studied classes of phytochemicals; phytosterols, isothiocyanates, and chlorophyll also have been investigated, although to a much lesser extent. Because there have been no systematic reviews of the literature on all phytochemicals and cancer risk to date, this article systematically reviews 96 published epidemiological studies that examined associations between phytochemicals and cancer risk. Most studies found null associations between individual phytochemicals and cancer risk at various sites. In addition, results from past studies have been largely inconsistent, and observed associations have been of relatively modest magnitude. The most consistent protective effects were observed for higher levels--dietary intake, serum, plasma, or urinary metabolites--of β-carotene and renal cell cancer, β-cryptoxanthin and lung cancer, isothiocyanates and lung cancer, isothiocyanates and gastrointestinal cancer, lignans and postmenopausal breast cancer, and flavonoids and lung cancer. Although elevated risk of certain cancers with higher levels of certain phytochemicals was observed, an insufficient pool of studies examining the same associations or inconsistent findings across studies limit the ability to conclude that any one phytochemical increases cancer risk. Additional research is needed to support previously identified associations in cases where only one study has examined a particular relationship. Importantly, continued research efforts are needed to evaluate the cumulative and interactive effects of numerous phytochemicals and phytochemical-rich foods on cancer risk.\",\n \"title\": \"Phytochemicals and cancer risk: a review of the epidemiological evidence.\"\n },\n {\n \"docid\": \"MED-2577\",\n \"text\": \"A case-control study probing the role of diet on the incidence of colorectal cancer was undertaken in Athens, Greece, in a population characterized by ethnic homogeneity but substantial heterogeneity with respect to dietary habits. The case series consisted of 100 consecutive patients with histologically confirmed colorectal cancer admitted to two large hospitals of Athens during a 16-month period; the control series consisted of orthopaedic patients, admitted to the same hospitals during the same time period, individually matched to the index cases by age and sex. Dietary histories concerning the frequency of consumption (per month or per week) of about 80 food items were obtained by the same interviewer. Cases reported significantly less frequent consumption of vegetables (particularly beets, spinach, lettuce and cabbage) and, independently, significantly more frequent consumption of meat (notably lamb and beef). Between the two extremes (high-vegetable, low-meat diet versus high-meat, low-vegetable diet) a risk ratio of about 8 appears to exist, sufficient (in size and direction) to explain a substantial part of the international variation in the incidence of colorectal cancer. Significant associations were not found with beer or other alcoholic beverages, and significant interactions were not noted with respect to age, sex and anatomic localization (colon vs. rectum).\",\n \"title\": \"Diet and colorectal cancer: a case-control study in Greece.\"\n },\n {\n \"docid\": \"MED-2579\",\n \"text\": \"There are now extensive scientific data suggesting the potential role of dietary and non-dietary phytochemicals in the prevention and control of prostate cancer (PCA) growth and progression. PCA is a disease of elderly male populations with a relatively slower rate of growth and progression as compared to most other cancers and, therefore, is a candidate disease for preventive intervention. Overall, PCA growth and progression involve aberrant mitogenic and survival signaling and deregulated cell cycle progression, accompanied by gradual accumulation of genetic and epigenetic changes over a period of years. Several mechanisms, including overexpression of growth, survival and angiogenic factors and their receptors, together with a loss/decrease of tumor suppressor p53, retinoblastoma and cyclin-dependent kinase inhibitor, have been implicated in PCA growth and progression. Therefore, phytochemicals targeting these molecular events could have a promising role in PCA prevention and/or therapy. Inositol hexaphosphate (IP6) is a major constituent of most cereals, legumes, nuts, oil seeds and soybean. Taken orally as an over-the-counter dietary/nutrient supplement, and is recognised as offering several health benefits without any known toxicity. In vitro anticancer efficacy of IP6 has been observed in many human, mouse and rat prostate cancer cells. Completed studies also show that oral feeding of IP6 inhibits human PCA xenograft growth in nude mice without toxicity. In a recently completed pilot study, we observed similar preventive effects of IP6 on prostate tumorigenesis in the TRAMP model. Mechanistic studies indicate that IP6 targets mitogenic and survival signaling, as well as cell cycle progression, in PCA cells. IP6 is also shown to target molecular events associated with angiogenesis. Moreover, IP6 has pleiotropic molecular targets for its overall efficacy against PCA and, therefore, could be a suitable candidate agent for preventive intervention of this malignancy in humans.\",\n \"title\": \"Prostate cancer and inositol hexaphosphate: efficacy and mechanisms.\"\n },\n {\n \"docid\": \"MED-2571\",\n \"text\": \"Background Prospective, randomized, pilot clinical study was conducted to evaluate the beneficial effects of inositol hexaphosphate (IP6) + Inositol in breast cancer patients treated with adjuvant therapy. Patients and methods Patients with invasive ductal breast cancer where polychemotherapy was indicated were monitored in the period from 2005-2007. Fourteen patients in the same stage of ductal invasive breast cancer were involved in the study, divided in two randomized groups. One group was subjected to take IP6 + Inositol while the other group was taking placebo. In both groups of patients the same laboratory parameters were monitored. When the treatment was finished, all patients have filled questionnaires QLQ C30 and QLQ-BR23 to determine the quality of life. Results Patients receiving chemotherapy, along with IP6 + Inositol did not have cytopenia, drop in leukocyte and platelet counts. Red blood cell counts and tumor markers were unaltered in both groups. However, patients who took IP6 + Inositol had significantly better quality of life (p = 0.05) and functional status (p = 0.0003) and were able to perform their daily activities. Conclusion IP6 + Inositol as an adjunctive therapy is valuable help in ameliorating the side effects and preserving quality of life among the patients treated with chemotherapy.\",\n \"title\": \"Efficacy of IP6 + inositol in the treatment of breast cancer patients receiving chemotherapy: prospective, randomized, pilot clinical study\"\n },\n {\n \"docid\": \"MED-3552\",\n \"text\": \"The study evaluated the protective effects of purple rice (Oryza sativa L.) bran extract (PRE) and its constituents, cyanidin and peonidin, against angiogenesis induced by vascular endothelial growth factor (VEGF). The effects of VEGF and PRE were examined by in vitro tube formation assays and following 14-day co-culture of human umbilical vein endothelial cells (HUVECs) and fibroblasts. The antiangiogenic mechanism of PRE was evaluated by VEGF-induced proliferation and migration of HUVECs and/or human retinal microvascular endothelial cells (HRMECs) and phosphorylation of extracellular signal-regulated kinase (ERK) and p38. The PRE significantly suppressed VEGF-induced tube formation, proliferation and migration in HUVECs and HRMECs as well as phosphorylation of ERK and p38. Cyanidin and peonidin also suppressed the proliferation and migration induced by VEGF. These findings indicate that PRE and anthocyanidins suppress VEGF-induced angiogenesis by inhibiting proliferation and migration and suggest that the inhibition of phosphorylated-ERK and -p38 may be involved in the underlying mechanism. Copyright © 2011 John Wiley & Sons, Ltd.\",\n \"title\": \"Purple rice (Oryza sativa L.) extract and its constituents inhibit VEGF-induced angiogenesis.\"\n },\n {\n \"docid\": \"MED-2570\",\n \"text\": \"The functional properties, including antioxidant and chemopreventative capacities as well as the inhibitory effects on angiotensin-converting enzyme (ACE), α-glucosidase and pancreatic lipase, of three Australian-grown faba bean genotypes (Nura, Rossa and TF(Ic*As)*483/13) were investigated using an array of in vitro assays. Chromatograms of on-line post column derivatisation assay coupled with HPLC revealed the existence of active phenolics (hump) in the coloured genotypes, which was lacking in the white-coloured breeding line, TF(Ic*As)*483/13. Roasting reduced the phenolic content, and diminished antioxidant activity by 10-40 % as measured by the reagent-based assays (diphenylpicrylhydrazyl, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) and oxygen radical absorbance capacity) in all genotypes. Cell culture-based antioxidant activity assay (cellular antioxidant activity) showed an increase of activity in the coloured genotypes after roasting. Faba bean extracts demonstrated cellular protection ability against H₂O₂-induced DNA damage (assessed using RAW264.7 cells), and inhibited the proliferation of all human cancer cell lines (BL13, AGS, Hep G2 and HT-29) evaluated. However, the effect of faba bean extracts on the non-transformed human cells (CCD-18Co) was negligible. Flow cytometric analyses showed that faba bean extracts successfully induced apoptosis of HL-60 (acute promyelocytic leukaemia) cells. The faba bean extracts also exhibited ACE, α-glucosidase and pancreatic lipase inhibitory activities. Overall, extracts from Nura (buff-coloured) and Rossa (red-coloured) were comparable, while TF(Ic*As)*483/13 (white-coloured) contained the lowest phenolic content and exhibited the least antioxidant and enzyme inhibition activities. These results are important to promote the utilisation of faba beans in human diets for various health benefits.\",\n \"title\": \"In vitro investigations of the potential health benefits of Australian-grown faba beans (Vicia faba L.): chemopreventative capacity and inhibitory ...\"\n },\n {\n \"docid\": \"MED-4090\",\n \"text\": \"Apple peel is a waste product from dried apple manufacture. The content of phenolic compounds, dietary fiber, and mineral are higher in apple peel, compared to other edible parts of this fruits. The objective of this study was to develop an ingredient from Granny Smith apple peel, using a pilot scale double drum-dryer, as drying technology. The control of all steps to maximize the retention of phenolic compounds and dietary fiber was considered. Operational conditions, such as drying temperature and time were determined, as well as important preprocessing steps like grinding and PPO inhibition. In addition, the physical-chemical characteristics, mineral and sugar content, and technological functional properties such as water retention capacity, solubility index, and dispersability among others, were analyzed. A simple, economical, and suitable pilot scale process, to produce a powder ingredient from apple peel by-product, was obtained. The drying process includes the application of ascorbic acid at 0.5% in the fresh apple peel slurry, drum-dryer operational conditions were 110 degrees C, 0.15 rpm and 0.2 mm drum clearance. The ingredient developed could be considered as a source of phenolic compounds (38.6 mg gallic acid equivalent/g dry base) and dietary fiber (39.7% dry base) in the formulation of foods. Practical Application: A method to develop an ingredient from Granny Smith apple peel using a pilot scale double drum-dryer as drying technology was developed. The method is simple, economical, feasible, and suitable and maximizes the retention of phenolic compounds and dietary fiber present in the raw matter. The ingredient could be used in the formulation of foods.\",\n \"title\": \"Development of an ingredient containing apple peel, as a source of polyphenols and dietary fiber.\"\n },\n {\n \"docid\": \"MED-3548\",\n \"text\": \"Cancer metastasis refers to the spread of cancer cells from the primary neoplasm to distant sites, where secondary tumors are formed, and is the major cause of death from cancer. Natural phytochemicals containing phenolic compounds have been widely demonstrated to have the capability to prevent cancer metastasis. Among phenolic compounds, flavonoids are a very large subclass, and they are abundant in food and nutraceuticals. The number of reports demonstrating that flavonoids are an effective natural inhibitor of cancer invasion and metastasis is increasing in the scientific literature. Catechin derivatives, (−)-epigallocatechin-3-gallate, (−)-epigallocatechin, (−)-epicatechin-3-gallate,and (−)-epicatechin, are the most studied compounds in this topic so far; genistein/genistin, silibinin, quercetin, and anthocyanin have also been widely investigated for their inhibitory activities on invasion/metastasis. Other flavonoids in dietary vegetable foods that are responsible for anti-invasive and anti-metastatic activities of tumors include luteolin,apigenin, myricetin, tangeretin, kaempferol, glycitein, licoricidin,daidzein, and naringenin. To effectively overcome the metastatic cascade, including cell-cell attachment, tissue barrier degradation, migration, invasion, cell-matrix adhesion,and angiogenesis, it is essential that a bioactive compound prevent tumor cells from metastasizing. This review summarizes the effects of flavonoids on the metastatic cascade and the related proteins, the in vitro anti-invasive activity of flavonoids against cancer cells, and the effects of flavonoids on antiangiogenic and in vivo anti-metastatic models. The available scientific evidence indicates that flavonoids are a ubiquitous dietary phenolics subclass and exert extensive in vitro anti-invasive and in vivo anti-metastatic activities.\",\n \"title\": \"Flavonoids, a ubiquitous dietary phenolic subclass, exert extensive in vitro anti-invasive and in vivo anti-metastatic activities.\"\n },\n {\n \"docid\": \"MED-2574\",\n \"text\": \"Inositol hexaphosphate (IP(6)) is a naturally occurring polyphosphorylated carbohydrate, abundantly present in many plant sources and in certain high-fiber diets, such as cereals and legumes. In addition to being found in plants, IP(6) is contained in almost all mammalian cells, although in much smaller amounts, where it is important in regulating vital cellular functions such as signal transduction, cell proliferation, and differentiation. For a long time IP(6) has been recognized as a natural antioxidant. Recently IP(6) has received much attention for its role in cancer prevention and control of experimental tumor growth, progression, and metastasis. In addition, IP(6) possesses other significant benefits for human health, such as the ability to enhance immune system, prevent pathological calcification and kidney stone formation, lower elevated serum cholesterol, and reduce pathological platelet activity. In this review we show the efficacy and discuss some of the molecular mechanisms that govern the action of this dietary agent. Exogenously administered IP(6) is rapidly taken up into cells and dephosphorylated to lower inositol phosphates, which further affect signal transduction pathways resulting in cell cycle arrest. A striking anticancer action of IP(6) was demonstrated in different experimental models. In addition to reducing cell proliferation, IP(6) also induces differentiation of malignant cells. Enhanced immunity and antioxidant properties also contribute to tumor cell destruction. Preliminary studies in humans show that IP(6) and inositol, the precursor molecule of IP(6), appear to enhance the anticancer effect of conventional chemotherapy, control cancer metastases, and improve quality of life. Because it is abundantly present in regular diet, efficiently absorbed from the gastrointestinal tract, and safe, IP(6) + inositol holds great promise in our strategies for cancer prevention and therapy. There is clearly enough evidence to justify the initiation of full-scale clinical trials in humans.\",\n \"title\": \"Protection against cancer by dietary IP6 and inositol.\"\n },\n {\n \"docid\": \"MED-3553\",\n \"text\": \"Several epidemiological studies have indicated that abundant consumption of foods from plant origin is associated with a reduced risk of developing several types of cancers. This chemopreventive effect is related to the high content of these foods in phytochemicals, such as polyphenols, that interfere with several processes involved in cancer progression including tumor cell growth, survival and angiogenesis. In addition to the low intake of plant-based foods, increased body mass and physical inactivity have recently emerged as other important lifestyle factors influencing cancer risk, leading to the generation of low-grade chronic inflammatory conditions which are a key process involved in tumor progression. The objectives of the current study are to investigate the inhibitory effects of these polyphenols on angiogenesis triggered by an inflammatory cytokine (IL-6) and to determine the mechanisms underlying this action. We found that, among the tested polyphenols, apigenin and luteolin were the most potent angiogenesis inhibitors through their inhibitory effect on the inflammatory cytokine IL-6/STAT3 pathway. These effects resulted in modulation of the activation of extracellular signal-regulated kinase-1/2 signaling triggered by IL-6, as well as in a marked reduction in the proliferation, migration and morphogenic differentiation of endothelial cells. Interestingly, these polyphenols also modulated the expression of IL-6 signal transducing receptor (IL-6Rα) and the secretion of the extracellular matrix degrading enzyme MMP-2 as well as the expression of suppressor of cytokine signaling (SOCS3) protein. Overall, these results may provide important new information on the role of diet in cancer prevention. Copyright © 2012 Elsevier Inc. All rights reserved.\",\n \"title\": \"Diet-derived polyphenols inhibit angiogenesis by modulating the interleukin-6/STAT3 pathway.\"\n },\n {\n \"docid\": \"MED-2583\",\n \"text\": \"Inositol hexaphosphate (IP(6)), a naturally polyphosphorylated carbohydrate, has been reported to have significant in vivo and in vitro anticancer activity against numerous tumours, such as colon, prostate, breast, liver and rhabdomyosarcomas. To confirm this activity in haematological malignancies and to characterize some of the mechanisms of IP(6) action, we analysed its effects on human leukaemic cell lines and fresh chronic myelogenous leukaemia (CML) progenitor cells using a combined cellular and molecular approach. IP(6) had a dose-dependent cytotoxic effect on all of the evaluated cell lines, with accumulation in the G2M phase in two out of five cell lines tested. At the molecular level, cDNA microarray analysis after IP(6) exposure showed an extensive downmodulation of genes involved in transcription and cell cycle regulation and a coherent upregulation of cell cycle inhibitors. Furthermore, IP(6) treatment of fresh leukaemic samples of bone marrow CD34+ CML progenitor cells significantly inhibited granulocyte-macrophage colony-forming unit (CFU-GM) formation (P = 0.0062) in comparison to normal bone marrow specimens, which were not affected. No differentiating effect on HL60 cells was observed. Taken together, our results confirm the antiproliferative activity of IP(6) and suggest that it may have a specific antitumour effect also in chronic myeloid leukaemias, via active gene modulation.\",\n \"title\": \"Effect of inositol hexaphosphate (IP(6)) on human normal and leukaemic haematopoietic cells.\"\n },\n {\n \"docid\": \"MED-2584\",\n \"text\": \"In a 6-year prospective study, the authors examined the relation between diet and incident colon cancer among 32,051 non-Hispanic white cohort members of the Adventist Health Study (California, 1976-1982) who, at baseline, had no documented or reported history of cancer. The risk of colon cancer was determined from proportional hazards regression with adjustment for age and other covariates. The authors found a positive association with total meat intake (risk ratio (RR) for > or =1 time/week vs. no meat intake = 1.85, 95% confidence interval (CI) 1.19-2.87; p for trend = 0.01) and, among subjects who favored specific types of meat, positive associations with red meat intake (RR for > or =1 time/week vs. no red meat intake = 1.90, 95% CI 1.16-3.11; p for trend = 0.02) and white meat intake (RR for > or =1 time/week vs. no white meat intake = 3.29, 95% CI 1.60-6.75; p for trend = 0.006). An inverse association with legume intake (RR for >2 times/week vs. <1 time/week = 0.53, 95% CI 0.33-0.86; p for trend = 0.03) was observed. Among men, a positive association with body mass index was observed (relative to the RR for tertile III (>25.6 kg/m2) vs. tertile I (<22.5 kg/m2) = 2.63, 95% CI 1.12-6.13; p for trend = 0.05). A complex relation was identified whereby subjects exhibiting a high red meat intake, a low legume intake, and a high body mass experienced a more than threefold elevation in risk relative to all other patterns based on these variables. This pattern of putative risk factors would likely contribute to increases in both insulin resistance (high body mass, high red meat intake) and glycemic load (low legume intake), a synergism that, if causal, implicates hyperinsulinemic exposure in colon carcinogenesis. The overall findings from this cohort identify both red meat intake and white meat intake as important dietary risk factors for colon cancer and raise the possibility that the risk due to red meat intake reflects a more complex etiology.\",\n \"title\": \"Dietary risk factors for colon cancer in a low-risk population.\"\n },\n {\n \"docid\": \"MED-4465\",\n \"text\": \"Adult stem cells of the mammary gland (MaSCs) are a highly dynamic population of cells that are responsible for the generation of the gland during puberty and its expansion during pregnancy. In recent years significant advances have been made in understanding how these cells are regulated during these developmentally important processes both in humans and in mice. Understanding how MaSCs are regulated is becoming a particularly important area of research, given that they may be particularly susceptible targets for transformation in breast cancer. Here, we summarize the identification of MaSCs, how they are regulated and the evidence for their serving as the origins of breast cancer. In particular, we focus on how changes in MaSC populations may explain both the increased risk of developing aggressive ER/PR(−) breast cancer shortly after pregnancy and the long-term decreased risk of developing ER/PR(+) tumors.\",\n \"title\": \"From milk to malignancy: the role of mammary stem cells in development, pregnancy and breast cancer\"\n },\n {\n \"docid\": \"MED-4464\",\n \"text\": \"Over the last decade, the notion that tumors are maintained by their own stem cells, the so-called cancer stem cells, has created great excitement in the research community. This review attempts to summarize the underlying concepts of this notion, to distinguish hard facts from beliefs and to define the future challenges of the field.\",\n \"title\": \"The cancer stem cell: premises, promises and challenges.\"\n },\n {\n \"docid\": \"MED-2559\",\n \"text\": \"Inositol hexaphosphate (IP6) has anti-cancer properties, but recently other extracellular functions have been observed for IP6, including enhancing superoxide production and phagocytosis by neutrophils in the presence of microbial stimuli. This study investigated other inflammatory functions of IP6 on adherent neutrophils. The effect of IP6 on the release of IL-8, tumour necrosis factor (TNF-alpha) and IL-6 by neutrophils attached to either plastic or laminin for up to 6 hours in response to stimulation with lipopolysaccharide or N-formyl-Met-Leu-Phe (fMLP) was investigated. An increase in IL-8 secretion by stimulated cells occurred in the presence of IP6. The incubation of cells attached to laminin with IP6 alone (100-250 BM) did not effect cell morphology, but in the presence of 10(-7) M fMLP altered cell shape. A direct effect of IP6 on cell function was to trigger a sustained assembly of F-actin. Thus, exposure of neutrophils to low levels of IP6 appears to modulate selective neutrophil functions.\",\n \"title\": \"Effect of IP6 on human neutrophil cytokine production and cell morphology.\"\n },\n {\n \"docid\": \"MED-3554\",\n \"text\": \"A great deal of effort is now being devoted to the development of new drugs that hopefully will control the spread of inoperable cancer by safely inhibiting tumor-evoked angiogenesis. However, there is growing evidence that certain practical nutritional measures have the potential to slow tumor angiogenesis, and it is reasonable to anticipate that, by combining several measures that work in distinct but complementary ways to impede the angiogenic process, a clinically useful 'multifocal angiostatic therapy' (MAT) might be devised. Several measures which might reasonably be included in such a protocol are discussed below, and include: a low-fat, low-glycemic index vegan diet, which may down-regulate the systemic IGF-I activity that supports angiogenesis; supplemental omega-3-rich fish oil, which has been shown to inhibit endothelial expression of Flk-1, a functionally crucial receptor for VEGF, and also can suppress tumor production of pro-angiogenic eicosanoids; high-dose selenium, which has recently been shown to inhibit tumor production of VEGF; green tea polyphenols, which can suppress endothelial responsiveness to both VEGF and fibroblast growth factor; and high-dose glycine, whose recently reported angiostatic activity may reflect inhibition of endothelial cell mitosis, possibly mediated by activation of glycine-gated chloride channels. In light of evidence that tumor-evoked angiogenesis has a high requirement for copper, copper depletion may have exceptional potential as an angiostatic measure, and is most efficiently achieved with the copper-chelating drug tetrathiomolybdate. If logistical difficulties make it difficult to acquire this experimental drug, high-dose zinc supplementation can achieve a slower depletion of the body's copper pool, and in any case can be used as maintenance therapy to maintain an adequate level of copper depletion. A provisional protocol is offered for a nutritionally based MAT entailing a vegan diet and supplemental intakes of fish oil, selenium, green tea polyphenols, glycine, and zinc. Inasmuch as cox-2 is overexpressed in many cancers, and cAMP can boost tumor production of various angiogenic factors as well as autogenous growth factors, adjunctive use of cox-2-specific NSAIDS may be warranted in some cases.\",\n \"title\": \"A wholly nutritional 'multifocal angiostatic therapy' for control of disseminated cancer.\"\n },\n {\n \"docid\": \"MED-4319\",\n \"text\": \"The article gives an overview of phytic acid in food and of its significance for human nutrition. It summarises phytate sources in foods and discusses problems of phytic acid/phytate contents of food tables. Data on phytic acid intake are evaluated and daily phytic acid intake depending on food habits is assessed. Degradation of phytate during gastro-intestinal passage is summarised, the mechanism of phytate interacting with minerals and trace elements in the gastro-intestinal chyme described and the pathway of inositol phosphate hydrolysis in the gut presented. The present knowledge of phytate absorption is summarised and discussed. Effects of phytate on mineral and trace element bioavailability are reported and phytate degradation during processing and storage is described. Beneficial activities of dietary phytate such as its effects on calcification and kidney stone formation and on lowering blood glucose and lipids are reported. The antioxidative property of phytic acid and its potentional anticancerogenic activities are briefly surveyed. Development of the analysis of phytic acid and other inositol phosphates is described, problems of inositol phosphate determination and detection discussed and the need for standardisation of phytic acid analysis in foods argued.\",\n \"title\": \"Phytate in foods and significance for humans: food sources, intake, processing, bioavailability, protective role and analysis.\"\n },\n {\n \"docid\": \"MED-2568\",\n \"text\": \"Inositol hexaphosphate (InsP6 or IP6) is ubiquitous. At 10 microM to 1 mM concentrations, IP6 and its lower phosphorylated forms (IP(1-5)) as well as inositol (Ins) are contained in most mammalian cells, wherein they are important in regulating vital cellular functions such as signal transduction, cell proliferation and differentiation. A striking anti-cancer action of IP6 has been demonstrated both in vivo and in vitro, which is based on the hypotheses that exogenously administered IP6 may be internalized, dephosphorylated to IP(1-5), and inhibit cell growth. There is additional evidence that Ins alone may further enhance the anti-cancer effect of IP6. Besides decreasing cellular proliferation, IP6 also causes differentiation of malignant cells often resulting in a reversion to normal phenotype. These data strongly point towards the involvement of signal transduction pathways, cell cycle regulatory genes, differentiation genes, oncogenes and perhaps, tumor suppressor genes in bringing about the observed anti-neoplastic action of IP6.\",\n \"title\": \"IP6: a novel anti-cancer agent.\"\n },\n {\n \"docid\": \"MED-2573\",\n \"text\": \"A significant anticancer activity of the naturally occurring carbohydrate inositol hexaphosphate (IP(6)) has been reported against numerous cancer models. Since tumors require angiogenesis for growth and metastasis, we hypothesize that IP(6) reduces tumor growth by inhibiting angiogenesis. Because angiogenesis depends on the interaction between endothelial and tumor cells, we investigated the effect of IP(6) on both. IP(6) inhibited the proliferation and induced the differentiation of endothelial cells in vitro; the growth of bovine aortic endothelial cells (BAECs) evaluated by MTT proliferation assay was inhibited in a dose-dependent manner (IC(50) = 0.74 mM). The combination of IP(6) and vasostatin, a calreticulin fragment with anti-angiogenic activity, was synergistically superior in growth inhibition than either compound. IP(6) inhibited human umbilical vein endothelial cell (HUVEC) tube formation (in vitro capillary differentiation) on a reconstituted extracellular matrix, Matrigel, and disrupted pre-formed tubes. IP(6) significantly reduced basic fibroblast growth factor (bFGF)-induced vessel formation (P < 0.01) in vivo in Matrigel plug assay. Exposure of HepG2, a human hepatoma cell line, to IP(6) for 8 h, resulted in a dose-dependent decrease in the mRNA levels of vascular endothelial growth factor (VEGF), as assessed by RT-PCR. IP(6) treatment of HepG2 cells for 24 h also significantly reduced the VEGF protein levels in conditioned medium, in a concentration-dependent manner (P = 0.012). Thus, IP(6) has an inhibitory effect on induced angiogenesis.\",\n \"title\": \"Anti-angiogenic activity of inositol hexaphosphate (IP6).\"\n },\n {\n \"docid\": \"MED-3550\",\n \"text\": \"Between 2000 and 2050, the number of new cancer patients diagnosed annually is expected to double, with an accompanying increase in treatment costs of more than $80 billion over just the next decade. Efficacious strategies for cancer prevention will therefore be vital for improving patients' quality of life and reducing healthcare costs. Judah Folkman first proposed antiangiogenesis as a strategy for preventing dormant microtumors from progressing to invasive cancer. Although antiangiogenic drugs are now available for many advanced malignancies (colorectal, lung, breast, kidney, liver, brain, thyroid, neuroendocrine, multiple myeloma, myelodysplastic syndrome), cost and toxicity considerations preclude their broad use for cancer prevention. Potent antiangiogenic molecules have now been identified in dietary sources, suggesting that a rationally designed antiangiogenic diet could provide a safe, widely available, and novel strategy for preventing cancer. This paper presents the scientific, epidemiologic, and clinical evidence supporting the role of an antiangiogenic diet for cancer prevention.\",\n \"title\": \"Tumor Angiogenesis as a Target for Dietary Cancer Prevention\"\n },\n {\n \"docid\": \"MED-2575\",\n \"text\": \"Introduction Matrix metalloproteinases (MMPs) have repeatedly been shown to play a very active role in extracellular matrix degradation associated with tumor invasion and metastasis. Tissue inhibitors of MMPs (TIMPs) are well-known for their ability to inhibit MMP activity thereby inhibiting malignant progression. Inositol hexaphosphate (IP6 phytic acid) has been recognized to have both preventive and therapeutic effects against various cancers including that of colon. In in vitro studies, IP6 has been demonstrated to inhibit cancer cell adhesion and migration. In the present study, the effect of IP6 on the expression of MMP and TIMP genes was evaluated in unstimulated and IL-1β-stimulated colon cancer cell line Caco-2. Materials and methods Real-time QRT-PCR was used to validate the transcription level of selected MMP and TIMP genes in Caco-2 cells after treatment with 1 ng/ml of IL-1β, 2.5 mM of IP6, and both for 6, 12, and 24 h. Results Stimulation of cells with IL-1β only resulted in an overexpression of MMP and their TIMP mRNAs. A significant decrease in MMP-13, MMP-3, MMP-2, and TIMP-1 basal expression was achieved by IP6. IP6 was also an efficient downregulator of MMP-1, MMP-9, and TIMP-2 genes transcription stimulated by IL-1β in 6 h lasting culture. After 12 h, IL-1β-induced MMP-2 mRNA expression was significantly reduced by IP6. Conclusion Proinflammatory cytokine IL-1β upregulates MMP and TIMP mRNAs expression in colon cancer epithelial cells Caco-2. IP6 (2.5 mM) influences constitutive expression of both MMP and TIMP genes and downregulates IL-1β stimulated transcription of some of these genes. IP6 exerts its anti-metastatic activity through modulation of MMP and TIMP genes expression to prevent cancer cell migration and invasion.\",\n \"title\": \"The effect of inositol hexaphosphate on the expression of selected metalloproteinases and their tissue inhibitors in IL-1β-stimulated colon cancer cells\"\n },\n {\n \"docid\": \"MED-2581\",\n \"text\": \"A hospital-based case-control study of diet and colorectal cancer was conducted among Chinese in Singapore (who constitute 77% of the population). A total of 203 cases and 425 controls were included. A history of the usual dietary intake one year prior to interview was taken using a quantitative food frequency questionnaire. Daily intakes of nutrients and selected food items were computed and stratified by tertiles of the control range, to assess risk in low-, medium- and high-intake categories. Effects were adjusted in analysis for age, sex, Chinese dialect group and occupation. For cancers of colon and rectum combined, significant observations were a protective effect of high cruciferous vegetable intake (OR = 0.50, p less than 0.01) and a predisposing effect of a high meat/vegetable consumption ratio (OR = 1.77, p less than 0.05). Similar results were observed for colon cancer alone. For rectal cancer alone (only 71 cases), significant (p less than 0.05) protective effects were observed for high intakes of protein (OR = 0.61), fibre (OR = 0.46), beta-carotene (OR = 0.54), cruciferous vegetables (OR = 0.51) and total vegetables (OR = 0.51). When further assessed by multiple logistic regression, tests for trend and assessment of risk in the extreme highest and lowest quintiles of the control range, the factors consistently significant were cruciferous vegetable intake and the meat/vegetable ratio. A particularly high relative risk was also noted in association with low coffee consumption (OR = 1.59, with p less than 0.05 for trend). No consistent trends were noted for fat or fibre intakes. For non-dietary variables investigated, a history of cholecystectomy increased the risk of both cancers combined (OR = 3.43, p less than 0.05) and colon cancer alone (OR = 4.39, p less than 0.01). This study in an Asian population of countries of Southern and Eastern Asia newly undergoing industrialization and in which rapid economic change is reflected in changing cancer patterns, suggests that the protective effects of certain dietary constituents, notably the cruciferous vegetables, may be more important than the hitherto stressed carcinogenic potential of fat and protein.\",\n \"title\": \"Colorectal cancer and diet in an Asian population--a case-control study among Singapore Chinese.\"\n },\n {\n \"docid\": \"MED-3551\",\n \"text\": \"Breast cancer is the leading cause of cancer-related deaths for women in the United States and the rest of the world. About 8% of women develop breast cancer during the course of their lives. Dietary habits are closely associated with both the risk and progression of breast cancer. Dietary agents have accumulated increasing importance with regards to the prevention and treatment of breast cancer. One such manner by which these compounds can target breast cancer development and progression is through interference with the angiogenic pathways. Angiogenesis is an intricate process that involves the development of new capillaries from previously existing blood vessels. Disruption of this pathway, therefore, provides a novel and effective avenue for therapeutic intervention of breast cancer. Various phytochemicals found in the diet kill breast cancer cells in vitro and prevent as well as suppress breast cancer progression in various preclinical animal models. This review examines the value of dietary phytoconstituents in the prevention and treatment of breast cancer through modulation of the intricate and complex process of angiogenesis. In addition, the potential benefits, challenges, and future directions of research on anti-angiogenic dietary phytochemicals in the prevention and intervention of breast cancer are also addressed. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.\",\n \"title\": \"Modulation of angiogenesis by dietary phytoconstituents in the prevention and intervention of breast cancer.\"\n },\n {\n \"docid\": \"MED-2578\",\n \"text\": \"The incidence of colonic cancer differs widely between various human populations. It has been suggested that dietary fiber content is of utmost importance and is inversely related to the occurrence of colonic cancer. However, high-fiber diets are not always correlated with low frequency of colonic cancer, suggesting the involvement of additional dietary constituents. Inositol hexaphosphate (phytic acid) is an abundant plant seed component present in many, but not all, fiber-rich diets. The authors have found that phytic acid is a potent inhibitor of iron-mediated generation of the hazardous oxidant, hydroxyl radical. Herein, the authors propose that inhibition of intracolonic hydroxyl radical generation, via the chelation of reactive iron by phytic acid, may help explain the suppression of colonic carcinogenesis and other inflammatory bowel diseases by diets rich in phytic acid.\",\n \"title\": \"Dietary suppression of colonic cancer. Fiber or phytate?\"\n },\n {\n \"docid\": \"MED-2988\",\n \"text\": \"This review describes the present state of knowledge about phytic acid (phytate), which is often present in legume seeds. The antinutritional effects of phytic acid primarily relate to the strong chelating associated with its six reactive phosphate groups. Its ability to complex with proteins and particularly with minerals has been a subject of investigation from chemical and nutritional viewpoints. The hydrolysis of phytate into inositol and phosphates or phosphoric acid occurs as a result of phytase or nonenzymatic cleavage. Enzymes capable of hydrolysing phytates are widely distributed in micro-organisms, plants and animals. Phytases act in a stepwise manner to catalyse the hydrolysis of phytic acid. To reduce or eliminate the chelating ability of phytate, dephosphorylation of hexa- and penta-phosphate forms is essential since a high degree of phosphorylation is necessary to bind minerals. There are several methods of decreasing the inhibitory effect of phytic acid on mineral absorption (cooking, germination, fermentation, soaking, autolysis). Nevertheless, inositol hexaphosphate is receiving increased attention owing to its role in cancer prevention and/or therapy and its hypocholesterolaemic effect.\",\n \"title\": \"The role of phytic acid in legumes: antinutrient or beneficial function?\"\n },\n {\n \"docid\": \"MED-2585\",\n \"text\": \"Inositol hexaphosphate (IP6) is a naturally occurring polyphosphorylated carbohydrate that is present in substantial amounts in almost all plant and mammalian cells. It was recently recognized to possess multiple biological functions. A striking anticancer effect of IP6 was demonstrated in different experimental models. Inositol is also a natural constituent possessing moderate anticancer activity. The most consistent and best anticancer results were obtained from the combination of IP6 plus inositol. In addition to reducing cell proliferation, IP6 increases differentiation of malignant cells, often resulting in a reversion to normal phenotype. Exogenously administered IP6 is rapidly taken into the cells and dephosphorylated to lower-phosphate inositol phosphates, which further interfere with signal transduction pathways and cell cycle arrest. Enhanced immunity and antioxidant properties can also contribute to tumor cell destruction. However, the molecular mechanisms underlying this anticancer action are not fully understood. Because it is abundantly present in regular diet, efficiently absorbed from the gastrointestinal tract, and safe, IP6 holds great promise in our strategies for the prevention and treatment of cancer. IP6 plus inositol enhances the anticancer effect of conventional chemotherapy, controls cancer metastases, and improves the quality of life, as shown in a pilot clinical trial. The data strongly argue for the use of IP6 plus inositol in our strategies for cancer prevention and treatment. However, the effectiveness and safety of IP6 plus inositol at therapeutic doses needs to be determined in phase I and phase II clinical trials in humans.\",\n \"title\": \"Cancer inhibition by inositol hexaphosphate (IP6) and inositol: from laboratory to clinic.\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"MED-3840","text":"The incidence of breast cancer is increasing in the Western world and there is an urgent need for studies of the mechanisms of sex steroids in order to develop novel preventive strategies. Diet modifications may be among the means for breast cancer prevention. Angiogenesis, key in tumor progression, is regulated by the balance between pro- and anti-angiogenic factors, which are controlled in the extracellular space. Sampling of these molecules at their bioactive compartment is therefore needed. The aims of this study were to explore if tamoxifen, one of the most used anti-estrogen treatments for breast cancer affected some of the most important endogenous angiogenesis regulators, vascular endothelial growth factor (VEGF), angiogenin, and endostatin in normal breast tissue in vivo and if a diet supplementation with flaxseed had similar effects as tamoxifen in the breast. Microdialysis was used for in situ sampling of extracellular proteins in normal breast tissue of women before and after six weeks of tamoxifen treatment or before and after addition of 25 g/day of ground flaxseed to the diet or in control women. We show significant correlations between estradiol and levels of VEGF, angiogenin, and endostatin in vivo, which was verified in ex vivo breast tissue culture. Moreover, tamoxifen decreased the levels of VEGF and angiogenin in the breast whereas endostatin increased significantly. Flaxseed did not alter VEGF or angiogenin levels but similar to tamoxifen the levels of endostatin increased significantly. We conclude that one of the mechanisms of tamoxifen in normal breast tissue include tipping of the angiogenic balance into an anti-angiogenic state and that flaxseed has limited effects on the pro-angiogenic factors whereas the anti-angiogenic endostatin may be modified by diet. Further studies of diet modifications for breast cancer prevention are warranted.","title":"Tamoxifen and Flaxseed Alter Angiogenesis Regulators in Normal Human Breast Tissue In Vivo"},{"docid":"MED-4224","text":"Metastatic, rather than primary tumours are responsible for ninety percent cancer deaths. Despite significant advances in the understanding of molecular and cellular mechanisms in tumour metastases, there are limitations in preventive treatment of metastatic tumours. Much evidence arising from laboratory and clinical studies suggests that growth factors and their receptors are implicated in cancer metastases development. We review the origin and production of growth factors and their receptors in all stages of cancer metastases including epithelial-mesenchymal transition, cancer cell invasion and migration, survival within the circulation, seeding at distant organs and metastatic tumour angiogenesis. The functions of growth factors and their receptors are also discussed. This review presents the efforts made in understanding this challenge to aid in the development of new treatment strategies for cancer metastases.","title":"Growth Factors and their receptors in cancer metastases."},{"docid":"MED-2818","text":"Curcumin is a polyphenol derived from the herbal remedy and dietary spice turmeric. It possesses diverse anti-inflammatory and anti-cancer properties following oral or topical administration. Apart from curcumin's potent antioxidant capacity at neutral and acidic pH, its mechanisms of action include inhibition of several cell signalling pathways at multiple levels, effects on cellular enzymes such as cyclooxygenase and glutathione S-transferases, immuno-modulation and effects on angiogenesis and cell-cell adhesion. Curcumin's ability to affect gene transcription and to induce apoptosis in preclinical models is likely to be of particular relevance to cancer chemoprevention and chemotherapy in patients. Although curcumin's low systemic bioavailability following oral dosing may limit access of sufficient concentrations for pharmacological effect in certain tissues, the attainment of biologically active levels in the gastrointestinal tract has been demonstrated in animals and humans. Sufficient data currently exist to advocate phase II clinical evaluation of oral curcumin in patients with invasive malignancy or pre-invasive lesions of the gastrointestinal tract, particularly the colon and rectum.","title":"Curcumin: the story so far."},{"docid":"MED-2817","text":"Curcumin (diferuloylmethane), a yellow coloring agent extracted from turmeric is also used as a remedy for the treatment and prevention of inflammatory diseases. Acute and chronic inflammation is a major factor in the progression of obesity, type II diabetes, arthritis, pancreatitis, cardiovascular, neurodegenerative and metabolic diseases, as well as certain types of cancer. Turmeric has a long history of use in Ayurvedic medicine for the treatment of inflammatory disorders. Recent studies on the efficacy and therapeutic applicability of turmeric have suggested that the active ingredient of tumeric is curcumin. Further, compelling evidence has shown that curcumin has the ability to inhibit inflammatory cell proliferation, invasion, and angiogenesis through multiple molecular targets and mechanisms of action. Curcumin is safe, non-toxic, and mediates its anti-inflammatory effects through the down-regulation of inflammatory transcription factors, cytokines, redox status, protein kinases, and enzymes that all promote inflammation. In addition, curcumin induces apoptosis through mitochondrial and receptor-mediated pathways, as well as activation of caspase cascades. In the current study, the anti-inflammatory effects of curcumin were evaluated relative to various chronic inflammatory diseases. Based on the available pharmacological data obtained from in vitro and in vivo research, as well as clinical trials, an opportunity exists to translate curcumin into clinics for the prevention of inflammatory diseases in the near future. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.","title":"Curcumin in inflammatory diseases."},{"docid":"MED-2507","text":"Increased plasma levels of adiponectin, metformin therapy of diabetes, rapamycin administration in transplant patients, and lifelong consumption of low-protein plant-based diets have all been linked to decreased risk for various cancers. These benefits may be mediated, at least in part, by down-regulated activity of the mTORC1 complex, a key regulator of protein translation. By boosting the effective availability of the translation initiator eIF4E, mTORC1 activity promotes the translation of a number of \"weak\" mRNAs that code for proteins, often up-regulated in cancer, that promote cellular proliferation, invasiveness, and angiogenesis, and that abet cancer promotion and chemoresistance by opposing apoptosis. Measures which inhibit eIF4E activity, either directly or indirectly, may have utility not only for cancer prevention, but also for the treatment of many cancers in which eIF4E drives malignancy. Since eIF4E is overexpressed in many cancers, strategies which target eIF4E directly--some of which are now being assessed clinically--may have the broadest efficacy in this regard. Many of the \"weak\" mRNAs coding for proteins that promote malignant behavior or chemoresistance are regulated transcriptionally by NF-kappaB and/or Stat3, which are active in a high proportion of cancers; thus, regimens concurrently targeting eIF4E, NF-kappaB, and Stat3 may suppress these proteins at both the transcriptional and translational levels, potentially achieving a very marked reduction in their expression. Copyright © 2011 Elsevier Ltd. All rights reserved.","title":"mTORC1 activity as a determinant of cancer risk--rationalizing the cancer-preventive effects of adiponectin, metformin, rapamycin, and low-protein ..."},{"docid":"MED-2824","text":"Cancer is primarily a disease of old age, and that life style plays a major role in the development of most cancers is now well recognized. While plant-based formulations have been used to treat cancer for centuries, current treatments usually involve poisonous mustard gas, chemotherapy, radiation, and targeted therapies. While traditional plant-derived medicines are safe, what are the active principles in them and how do they mediate their effects against cancer is perhaps best illustrated by curcumin, a derivative of turmeric used for centuries to treat a wide variety of inflammatory conditions. Curcumin is a diferuloylmethane derived from the Indian spice, turmeric (popularly called \"curry powder\") that has been shown to interfere with multiple cell signaling pathways, including cell cycle (cyclin D1 and cyclin E), apoptosis (activation of caspases and down-regulation of antiapoptotic gene products), proliferation (HER-2, EGFR, and AP-1), survival (PI3K/AKT pathway), invasion (MMP-9 and adhesion molecules), angiogenesis (VEGF), metastasis (CXCR-4) and inflammation (NF-kappaB, TNF, IL-6, IL-1, COX-2, and 5-LOX). The activity of curcumin reported against leukemia and lymphoma, gastrointestinal cancers, genitourinary cancers, breast cancer, ovarian cancer, head and neck squamous cell carcinoma, lung cancer, melanoma, neurological cancers, and sarcoma reflects its ability to affect multiple targets. Thus an \"old-age\" disease such as cancer requires an \"age-old\" treatment.","title":"Curcumin and cancer: an \"old-age\" disease with an \"age-old\" solution."},{"docid":"MED-2922","text":"Overwhelming evidence suggests that edible small and soft-fleshed berry fruits may have beneficial effects against several types of human cancers. The anticancer potential of berries has been related, at least in part, to a multitude of bioactive phytochemicals that these colorful fruits contain, including polyphenols (flavonoids, proanthocyanidins, ellagitannins, gallotannins, phenolic acids), stilbenoids, lignans, and triterpenoids. Studies show that the anticancer effects of berry bioactives are partially mediated through their abilities to counteract, reduce, and also repair damage resulting from oxidative stress and inflammation. In addition, berry bioactives also regulate carcinogen and xenobiotic metabolizing enzymes, various transcription and growth factors, inflammatory cytokines, and subcellular signaling pathways of cancer cell proliferation, apoptosis, and tumor angiogenesis. Berry phytochemicals may also potentially sensitize tumor cells to chemotherapeutic agents by inhibiting pathways that lead to treatment resistance, and berry fruit consumption may provide protection from therapy-associated toxicities. Although a wide variety of berry fruits are consumed worldwide, this paper focuses on those commonly consumed in North America, namely, blackberries, black raspberries, blueberries, cranberries, red raspberries, and strawberries. In addition, a large body of studies on singly purified berry bioactives is available, but this paper focuses on studies of \"whole berries\" per se, that is, as berry extracts and purified fractions, juices, and freeze-dried powders. Potential mechanisms of anticancer action and bioavailability of berry phenolics, as well as gaps in knowledge and recommendations for future berry research, are also briefly discussed.","title":"Berry fruits for cancer prevention: current status and future prospects."},{"docid":"MED-2357","text":"Patients with cancer have circulating heterophile antibodies that agglutinate animal red cells via recognition of the mammalian cell surface sialic acid N-glycolylneuraminic acid (Neu5Gc), which was long considered an oncofetal antigen in humans. However, humans are genetically deficient in Neu5Gc production and instead metabolically accumulate Neu5Gc from dietary sources, particularly red meats and milk products. Moreover, mice with a human-like defect showed no alternate pathway for Neu5Gc synthesis and even normal humans express anti-Neu5Gc antibodies. We show here that human tumors accumulate Neu5Gc that is covalently attached to multiple classes of glycans. The paradox of human tumor Neu5Gc accumulation in the face of circulating anti-Neu5Gc antibodies was hypothesized to be due to facilitation of tumor progression by the resulting low-grade chronic inflammation. Indeed, murine tumors expressing human-like levels of Neu5Gc show accelerated growth in syngeneic mice with a human-like Neu5Gc deficiency, coincident with the induction of anti-Neu5Gc antibodies and increased infiltration of inflammatory cells. Transfer of polyclonal monospecific syngeneic mouse anti-Neu5Gc serum also enhanced growth of transplanted syngeneic tumors bearing human-like levels of Neu5Gc, with tumors showing evidence for antibody deposition, enhanced angiogenesis and chronic inflammation. These effects were suppressed by a cyclooxygenase-2 inhibitor, a drug type known to reduce human carcinoma risk. Finally, affinity-purified human anti-Neu5Gc antibodies also accelerate growth of Neu5Gc-containing tumors in Neu5Gc-deficient mice. Taken together, the data suggest that the human propensity to develop diet-related carcinomas is contributed to by local chronic inflammation, resulting from interaction of metabolically-accumulated dietary Neu5Gc with circulating anti-Neu5Gc antibodies.","title":"Evidence for a human-specific mechanism for diet and antibody-mediated inflammation in carcinoma progression"},{"docid":"MED-3878","text":"Diet, nutritional status, and certain dietary supplements are postulated to influence the development and progression of prostate cancer. Angiogenesis and inflammation are central to tumor growth and progression, but the effect of diet on these processes remains uncertain. We explored changes in 50 plasma cytokines and angiogenic factors (CAFs) in 145 men with prostate cancer enrolled in a pre-operative, randomized controlled phase-II trial with four arms: control (usual diet); low-fat (LF) diet; flaxseed-supplemented (FS) diet; and flaxseed-supplemented, low-fat diet. The mean duration of dietary intervention was 30–31 days. Among the individual arms, the largest number of significant changes (baseline vs pre-operative follow-up) was observed in the LF arm, with 19 CAFs decreasing and one increasing (p<.05). Compared to the control arm, 6 CAFs—including pro-angiogenic factors (stromal-cell derived-1α and myeloid factors (granulocyte-colony-stimulating factor, macrophage colony-stimulating factor — all decreased in the LF arm compared to controls; 3 and 4 CAFs changed in the FS and FS+LF arms, respectively. Weight loss occurred in the LF arms and significantly correlated with VEGF decreases (P <0.001). The CAFs that changed in the LF arm are all known to be regulated by nuclear factor-kappa B (NF-κB), and a pathway analysis identified NF-κB as the most likely regulatory network associated with these changes in the LF arm, but not in the FS-containing arms. These results suggest that a low-fat diet without flaxseed may reduce levels of specific inflammatory cytokines and angiogenic factors and suggests that the NF-κB pathway may be a mediator of these changes.","title":"Effect of Low-fat Diets on Plasma Levels of NFκB-regulated Inflammatory Cytokines and Angiogenic Factors in Men with Prostate Cancer"},{"docid":"MED-3721","text":"Reduced expression of proapoptotic and terminal differentiation genes in conjunction with increased levels of the proinflammatory and angiogenesis-inducing enzymes, cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS), correlate with malignant transformation of oral intraepithelial neoplasia (IEN). Accordingly, this study investigated the effects of a 10% (w/w) freeze-dried black raspberry gel on oral IEN histopathology, gene expression profiles, intraepithelial COX-2 and iNOS proteins, and microvascular densities. Our laboratories have shown that freeze-dried black raspberries possess antioxidant properties and also induce keratinocyte apoptosis and terminal differentiation. Oral IEN tissues were hemisected to provide samples for pretreatment diagnoses and establish baseline biochemical and molecular variables. Treatment of the remaining lesional tissue (0.5 g gel applied four times daily for 6 weeks) began 1 week after the initial biopsy. RNA was isolated from snap-frozen IEN lesions for microarray analyses, followed by quantitative reverse transcription-PCR validation. Additional epithelial gene-specific quantitative reverse transcription-PCR analyses facilitated the assessment of target tissue treatment effects. Surface epithelial COX-2 and iNOS protein levels and microvascular densities were determined by image analysis quantified immunohistochemistry. Topical berry gel application uniformly suppressed genes associated with RNA processing, growth factor recycling, and inhibition of apoptosis. Although the majority of participants showed posttreatment decreases in epithelial iNOS and COX-2 proteins, only COX-2 reductions were statistically significant. These data show that berry gel application modulated oral IEN gene expression profiles, ultimately reducing epithelial COX-2 protein. In a patient subset, berry gel application also reduced vascular densities in the superficial connective tissues and induced genes associated with keratinocyte terminal differentiation.","title":"Topical Application of a Bioadhesive Black Raspberry Gel Modulates Gene Expression and Reduces Cyclooxygenase 2 Protein in Human Premalignant Oral Lesions"},{"docid":"MED-3702","text":"BACKGROUND: Increased prevalence of allergic diseases in western societies has been described as an epidemic. The precise turning point for the epidemic and the antigens responsible for it remain obscure. OBJECTIVE: To evaluate how the prevalence of atopic disease has changed in terms of detectable sensitization to aeroallergens and dietary allergens in a cross-sectional comparison of subjects from birth cohorts more than 60 years apart. METHODS: We studied four groups of 100 subjects each (at ages 7, 27, 47 and 67 years), representing those born in 1990, 1963-66, 1943-46 and in 1923-26, respectively. Serum total and specific IgE concentrations against aeroallergens and dietary allergens were determined. A questionnaire elicited information on symptoms, allergic diseases and medication. RESULTS: The proportion of subjects with detectable IgE antibodies against aeroallergens increased consistently from the oldest to the youngest birth cohorts; chi2 trend=56.809, P<0.0001. Similar progression was not seen in sensitization to dietary allergens. The proportion of those with diagnosed asthma differed significantly (chi2=13.45, P=0.004) across the birth cohorts. The lowest prevalence of asthma and sensitization to dietary allergens was detected in those born in 1943-46, i.e. during or immediately after World War II. CONCLUSION: Prevalence of sensitization to airborne allergens, unlike that to dietary allergens, has increased over a long period of time. Our results support the concept of the immune function being programmed by external factors early in life. They also call for caution when interpretations of the pace and possible causes of the allergy epidemic are made on the basis of short-term studies.","title":"The allergy epidemic extends beyond the past few decades."},{"docid":"MED-3541","text":"OBJECTIVE: The study evaluated the association between consumption frequencies of the major food categories and the risk of new depression four years later in older Taiwanese. DESIGN: A prospective cohort study with multistage random sampling. Logistic regression analysis evaluated the significance of the longitudinal associations of intake frequencies of the major food categories with future (4 years later) risk of new depression, controlled for possible confounding factors with or without adjustment for cognitive status. SETTING: Population-based free-living elderly. SUBJECTS: Men and women (n 1609) ≥65 years of age. RESULTS: In a regression model that controlled for demographic, socio-economic, lifestyle and disease/health-related variables but not cognitive status, both fruits (OR = 0·66, 95 % CI 0·45, 0·98, P = 0·038) and vegetables (OR = 0·38, 95 % CI 0·17, 0·86, P = 0·021) were protective against depressive symptoms 4 years later. However, when the same regression model was also adjusted for cognitive status, only vegetables (OR = 0·40, 95 % CI 0·17, 0·95, P = 0·039) were protective against depressive symptoms. Higher consumption of eggs was close to being significant in both regression models (P = 0·087 and 0·069, respectively). Other food categories including meat/poultry, fish, seafood, dairy, legumes, grains and tea showed no significant associations. CONCLUSIONS: Results suggest that although confounding factors cannot be totally ruled out, more frequent consumption of vegetables seems to be protective against depressive symptoms in the elderly. Further studies are needed to elucidate the causal role and the mechanism of the association.","title":"Frequent consumption of vegetables predicts lower risk of depression in older Taiwanese - results of a prospective population-based study."},{"docid":"MED-5122","text":"BACKGROUND: Drinking mate has been associated with cancers of the esophagus, oropharynx, larynx, lung, kidney, and bladder. We conducted this study to determine whether drinking mate could lead to substantial exposure to polycyclic aromatic hydrocarbons (PAH), including known carcinogens, such as benzo[a]pyrene. METHODS: The concentrations of 21 individual PAHs were measured in dry leaves of eight commercial brands of yerba mate and in infusions made with hot (80 degrees C) or cold (5 degrees C) water. Measurements were done using gas chromatography/mass spectrometry, with deuterated PAHs as the surrogates. Infusions were made by adding water to the leaves, removing the resulting infusion after 5 min, and then adding more water to the remaining leaves. This process was repeated 12 times for each infusion temperature. RESULTS: The total concentrations of the 21 PAHs in different brands of yerba mate ranged from 536 to 2,906 ng/g dry leaves. Benzo[a]pyrene concentrations ranged from 8.03 to 53.3 ng/g dry leaves. For the mate infusions prepared using hot water and brand 1, 37% (1,092 of 2,906 ng) of the total measured PAHs and 50% (25.1 of 50 ng) of the benzo[a]pyrene content were released into the 12 infusions. Similar results were obtained for other hot and cold infusions. CONCLUSION: Very high concentrations of carcinogenic PAHs were found in yerba mate leaves and in hot and cold mate infusions. Our results support the hypothesis that the carcinogenicity of mate may be related to its PAH content.","title":"High levels of carcinogenic polycyclic aromatic hydrocarbons in mate drinks."},{"docid":"MED-4722","text":"BACKGROUND: There has been a resurgence of interest in the controversial relation between dietary protein and bone health. OBJECTIVE: This article reports on the first systematic review and meta-analysis of the relation between protein and bone health in healthy human adults. DESIGN: The MEDLINE (January 1966 to September 2007) and EMBASE (1974 to July 2008) databases were electronically searched for all relevant studies of healthy adults; studies of calcium excretion or calcium balance were excluded. RESULTS: In cross-sectional surveys, all pooled r values for the relation between protein intake and bone mineral density (BMD) or bone mineral content at the main clinically relevant sites were significant and positive; protein intake explained 1-2% of BMD. A meta-analysis of randomized placebo-controlled trials indicated a significant positive influence of all protein supplementation on lumbar spine BMD but showed no association with relative risk of hip fractures. No significant effects were identified for soy protein or milk basic protein on lumbar spine BMD. CONCLUSIONS: A small positive effect of protein supplementation on lumbar spine BMD in randomized placebo-controlled trials supports the positive association between protein intake and bone health found in cross-sectional surveys. However, these results were not supported by cohort study findings for hip fracture risk. Any effects found were small and had 95% CIs that were close to zero. Therefore, there is a small benefit of protein on bone health, but the benefit may not necessarily translate into reduced fracture risk in the long term.","title":"Dietary protein and bone health: a systematic review and meta-analysis."},{"docid":"MED-1118","text":"OBJECTIVE: To measure Proteus mirabilis and Escherichia coli antibody levels in patients with rheumatoid arthritis (RA) during treatment by vegetarian diet. METHODS: Sera were collected from 53 RA patients who took part in a controlled clinical trial of fasting and a one year vegetarian diet. P mirabilis and E coli antibody levels were measured by an indirect immunofluorescence technique and an enzyme immunoassay, respectively. RESULTS: The patients on the vegetarian diet had a significant reduction in the mean anti-proteus titres at all time points during the study, compared with baseline values (all p < 0.05). No significant change in titre was observed in patients who followed an omnivorous diet. The decrease in anti-proteus titre was greater in the patients who responded well to the vegetarian diet compared with diet non-responders and omnivores. The total IgG concentration and levels of antibody against E coli, however, were almost unchanged in all patient groups during the trial. The decrease from baseline in proteus antibody levels correlated significantly (p < 0.001) with the decrease in a modified Stoke disease activity index. CONCLUSION: The decrease in P mirabilis antibody levels in the diet responders and the correlation between the decrease in proteus antibody level and decrease in disease activity supports the suggestion of an aetiopathogenetic role for P mirabilis in RA.","title":"Decrease in anti-Proteus mirabilis but not anti-Escherichia coli antibody levels in rheumatoid arthritis patients treated with fasting and a one year vegetarian diet."},{"docid":"MED-3177","text":"Neurocysticercosis (NCC) is an infection of the central nervous system (CNS) caused by the metacestode larval form of the parasite Taenia sp. Many factors can contribute to the endemic nature of cysticercosis. The inflammatory process that occurs in the tissue surrounding the parasite and/or distal from it can result from several associated mechanisms and may be disproportionate with the number of cysts. This discrepancy may lead to difficulty with the proper diagnosis in people from low endemic regions or regions that lack laboratory resources. In the CNS, the cysticerci have two basic forms, isolated cysts (Cysticercus cellulosae=CC) and racemose cysts (Cysticercus racemosus=CR), and may be meningeal, parenchymal, or ventricular or have a mixed location. The clinical manifestations are based on two fundamental syndromes that may occur in isolation or be associated: epilepsy and intracranial hypertension. They may be asymptomatic, symptomatic or fatal; have an acute, sub-acute or chronic picture; or may be in remission or exacerbated. The cerebrospinal fluid (CSF) may be normal, even in patients with viable cysticerci, until the patients begin to exhibit the classical syndrome of NCC in the CSF, or show changes in one or more routine analysed parameters. Computed tomography (CT) and magnetic resonance imaging (MRI) have allowed non-invasive diagnoses, but can lead to false negatives. Treatment is a highly controversial issue and is characterised by individualised therapy sessions. Two drugs are commonly used, praziquantel (PZQ) and albendazole (ABZ). The choice of anti-inflammatory drugs includes steroids and dextrochlorpheniramine (DCP). Hydrocephalus is a common secondary effect of NCC. Surgical cases of hydrocephalus must be submitted to ventricle-peritoneal shunt (VPS) immediately before cysticidal treatment, and surgical extirpation of the cyst may lead to an absence of the surrounding inflammatory process. The progression of NCC may be simple or complicated, have remission with or without treatment and may exhibit symptoms that can disappear for long periods of time or persist until death. Unknown, neglected and controversial aspects of NCC, such as the impaired fourth ventricle syndrome, the presence of chronic brain oedema and psychic complaints, in addition to the lack of detectable glucose in the CSF and re-infection are discussed.","title":"Neurocysticercosis: the enigmatic disease."},{"docid":"MED-4351","text":"The past decade has seen an explosion in research focusing on innate immunity. Through a wide range of mechanisms including phagocytosis, intracellular killing, and activation of pro-inflammatory or antiviral cytokine production via pattern recognition receptors, the cells of the innate immune system initiate and support adaptive immunity. The effects of aging on innate immune responses remain incompletely understood, particularly in humans. Here, we review advances in the study of human immunosenescence in the diverse cells of the innate immune system, including neutrophils, monocytes, macrophages, NK and NKT cells, and dendritic cells—with a focus on consequences for the response to infection or vaccination in old age.","title":"Human innate Immunosenescence: causes and consequences for immunity in old age"},{"docid":"MED-1038","text":"We examined effects of fiber on stool output, since this is one of the primary mediating variables for the hypothesized relationship between fiber and disease. Total neutral detergent fiber in the dietary fiber source was predictive of stool weight but not frequency. Substantial individual differences in stool output remained when dietary factors were controlled. Personality measures were used to predict stool weight and frequency independently of diet, and accounted for about as much variance in stool output as did dietary fiber. These results suggest that personality factors predispose some persons to low stool output. These individuals may benefit particularly from dietary fiber.","title":"Dietary fiber and personality factors as determinants of stool output."},{"docid":"MED-983","text":"BACKGROUND: Our goal was to forecast the global burden of Alzheimer's disease and evaluate the potential impact of interventions that delay disease onset or progression. METHODS: A stochastic, multistate model was used in conjunction with United Nations worldwide population forecasts and data from epidemiological studies of the risks of Alzheimer's disease. RESULTS: In 2006, the worldwide prevalence of Alzheimer's disease was 26.6 million. By 2050, the prevalence will quadruple, by which time 1 in 85 persons worldwide will be living with the disease. We estimate about 43% of prevalent cases need a high level of care, equivalent to that of a nursing home. If interventions could delay both disease onset and progression by a modest 1 year, there would be nearly 9.2 million fewer cases of the disease in 2050, with nearly the entire decline attributable to decreases in persons needing a high level of care. CONCLUSIONS: We face a looming global epidemic of Alzheimer's disease as the world's population ages. Modest advances in therapeutic and preventive strategies that lead to even small delays in the onset and progression of Alzheimer's disease can significantly reduce the global burden of this disease.","title":"Forecasting the global burden of Alzheimer's disease."},{"docid":"MED-2757","text":"BACKGROUND: Multivitamins are the most commonly used supplement in the developed world. Recent epidemiologic findings suggest that multivitamin use increases the risk of mortality. OBJECTIVE: We aimed to determine whether multivitamin-multimineral treatment, used for primary or secondary prevention, increases the risk of mortality in independently living adults. DESIGN: We performed a meta-analysis of randomized controlled trials. Multiple electronic databases were systematically searched from March to October 2012. Randomized controlled primary or secondary prevention trials were considered for inclusion. Eligible trials investigated daily multivitamin-multimineral supplementation for ≥1 y. Cohorts described as institutionalized or as having terminal illness (tertiary prevention) were excluded. The number of deaths and the sample size of each study arm were extracted independently by 2 researchers. Twenty-one articles were included in the analysis, which generated a total pooled sample of 91,074 people and 8794 deaths. These trials were pooled in a meta-analysis, and the outcomes were expressed as RRs and 95% CIs. RESULTS: The average age of the pooled sample was 62 y, and the average duration of supplementation was 43 mo. Across all studies, no effect of multivitamin-multimineral treatment on all-cause mortality (RR: 0.98; 95% CI: 0.94, 1.02) was observed. There was a trend for a reduced risk of all-cause mortality across primary prevention trials (RR: 0.94; 95% CI: 0.89, 1.00). Multivitamin-multimineral treatment had no effect on mortality due to vascular causes (RR: 1.01; 95% CI: 0.93, 1.09) or cancer (RR: 0.96; 95% CI: 0.88, 1.04). No statistical evidence of heterogeneity or publication bias was observed. CONCLUSION: Multivitamin-multimineral treatment has no effect on mortality risk.","title":"Multivitamin-multimineral supplementation and mortality: a meta-analysis of randomized controlled trials."},{"docid":"MED-1200","text":"Oxidative stress has been implicated in the pathophysiology of many neuropsychiatric disorders such as schizophrenia, bipolar disorder, major depression etc. Both genetic and nongenetic factors have been found to cause increased cellular levels of reactive oxygen species beyond the capacity of antioxidant defense mechanism in patients of psychiatric disorders. These factors trigger oxidative cellular damage to lipids, proteins and DNA, leading to abnormal neural growth and differentiation. Therefore, novel therapeutic strategies such as supplementation with antioxidants can be effective for long-term treatment management of neuropsychiatric disorders. The use of antioxidants and PUFAs as supplements in the treatment of neuropsychiatric disorders has provided some promising results. At the same time, one should be cautious with the use of antioxidants since excessive antioxidants could dangerously interfere with some of the protective functions of reactive oxygen species. The present article will give an overview of the potential strategies and outcomes of using antioxidants as therapeutics in psychiatric disorders.","title":"Antioxidants as potential therapeutics for neuropsychiatric disorders"},{"docid":"MED-1131","text":"To clarify the role of the faecal flora in the diet-induced decrease of rheumatoid arthritis (RA) activity, 43 RA patients were randomized into two groups: the test group to receive living food, a form of uncooked vegan diet rich in lactobacilli, and the control group to continue their ordinary omnivorous diets. Based on clinical assessments before, during and after the intervention period, a disease improvement index was constructed for each patient. According to the index, patients were assigned either to a group with a high improvement index (HI) or to a group with a low improvement index (LO). Stool samples collected from each patient before the intervention and at 1 month were analysed by direct stool sample gas-liquid chromatography of bacterial cellular fatty acids. This method has proved to be a simple and sensitive way to detect changes and differences in the faecal microbial flora between individual stool samples or groups of them. A significant, diet-induced change in the faecal flora (P = 0.001) was observed in the test group, but not in the control group. Further, in the test group, a significant (P = 0.001) difference was detected between the HI and LO categories at 1 month, but not in the pre-test samples. We conclude that a vegan diet changes the faecal microbial flora in RA patients, and changes in the faecal flora are associated with improvement in RA activity.","title":"Faecal microbial flora and disease activity in rheumatoid arthritis during a vegan diet."},{"docid":"MED-1786","text":"Fertility status may predict later mortality, but no studies have examined the effect of semen quality on subsequent mortality. Men referred to the Copenhagen Sperm Analysis Laboratory by general practitioners and urologists from 1963 to 2001 were, through a unique personal identification number, linked to the Danish central registers that hold information on all cases of cancer, causes of death, and number of children in the Danish population. The men were followed until December 31, 2001, death, or censoring, whichever occurred first, and the total mortality and cause-specific mortality of the cohort were compared with those of all age-standardized Danish men or according to semen characteristics. Among 43,277 men without azospermia referred for infertility problems, mortality decreased as the sperm concentration increased up to a threshold of 40 million/mL. As the percentages of motile and morphologically normal spermatozoa and semen volume increased, mortality decreased in a dose-response manner (P(trend) < 0.05). The decrease in mortality among men with good semen quality was due to a decrease in a wide range of diseases and was found among men both with and without children; therefore, the decrease in mortality could not be attributed solely to lifestyle and/or social factors. Semen quality may therefore be a fundamental biomarker of overall male health.","title":"Good semen quality and life expectancy: a cohort study of 43,277 men."},{"docid":"MED-5361","text":"OBJECTIVE: To compare 2 omega-3 (n-3) preparations enriched with eicosapentaenoic acid (EPA) versus docosahexaenoic acid (DHA) as monotherapy for major depressive disorder (MDD) in a 2-site, placebo-controlled, randomized, double-blind clinical trial. METHOD: 196 adults (53% female; mean [SD] age = 44.7 [13.4] years) with DSM-IV MDD and a baseline 17-item Hamilton Depression Rating Scale (HDRS-17) score ≥ 15 were randomized equally from May 18, 2006, to June 30, 2011, to 8 weeks of double-blind treatment with oral EPA-enriched n-3 1000 mg/d, DHA-enriched n-3 1,000 mg/d, or placebo. RESULTS: 154 subjects completed the study. Modified intent-to-treat (mITT) analysis (n = 177 subjects with ≥ 1 postbaseline visit; 59.3% female, mean [SD] age 45.8 [12.5] years) employed mixed-model repeated measures (MMRM). All 3 groups demonstrated statistically significant improvement in the HDRS-17 (primary outcome measure), 16-item Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR-16), and Clinical Global Improvement-Severity Scale (CGI-S) (P < .05), but neither n-3 preparation separated from placebo (P > .05). Response and remission rates were in the range of 40%-50% and 30%, respectively, for all treatments, with no significant differences between groups. One subject receiving EPA-enriched n-3 discontinued due to worsening depression, and 1 subject receiving placebo discontinued due to an unspecified \"negative reaction\" to pills. CONCLUSIONS: Neither EPA-enriched nor DHA-enriched n-3 was superior to placebo for the treatment of MDD. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00517036. © Copyright 2015 Physicians Postgraduate Press, Inc.","title":"A double-blind, randomized controlled clinical trial comparing eicosapentaenoic acid versus docosahexaenoic acid for depression."},{"docid":"MED-2658","text":"The prevalence of allergic diseases has increased in recent decades. Allergic diseases, particularly asthma, are complex diseases with strong gene-environment interactions. Epidemiological studies have identified a variety of risk factors for the development of allergic diseases. Among them, endocrine-disrupting chemicals (EDCs) play an important role in triggering or exacerbating these diseases. 4-Nonylphenol (NP) and 4-octylphenol (OP)--two major alkylphenols--have been recognized as common toxic and xenobiotic endocrine disrupters. Due to their low solubility, high hydrophobicity, and low estrogenic activity, they tend to accumulate in the human body and may be associated with the adverse effects of allergic diseases. Recently, new evidence has supported the importance of alkylphenols in the in vitro allergic response. This review focuses on the effects of alkylphenols on several key cell types in the context of allergic inflammation. Copyright © 2012. Published by Elsevier B.V.","title":"Alkylphenols--potential modulators of the allergic response."},{"docid":"MED-3637","text":"There are over 750 species of bacteria that inhabit the human oral cavity, but only a small fraction of those are attributed to causing plaque-related diseases such as caries. Streptococcus mutans is accepted as the main cariogenic agent and there is substantial knowledge regarding the specific virulence factors that render the organism a pathogen. There has been rising interest in alternative, target-specific treatment options as opposed to nonspecific mechanical plaque removal or application of broad-spectrum antibacterials that are currently in use. The impact of diet on oral health is undeniable, and this is directly observable in populations that consume high quantities of polyphenol-rich foods or beverages. Such populations have low caries incidence and better overall oral health. Camellia sinensis, the plant from which various forms of tea are derived, and Vaccinium macrocarpon (American cranberry fruit) have received notable attention both for their prevalence in the human diet as well as for their unique composition of polyphenols. The biologically active constituents of these plants have demonstrated potent enzyme-inhibitory properties without being bactericidal, a key quality that is important in developing therapies that will not cause microorganisms to develop resistance. The aim of this review is to consider studies that have investigated the feasibility of tea, cranberry, and other select plant derivatives as a potential basis for alternative therapeutic agents against Streptococcus mutans and to evaluate their current and future clinical relevance.","title":"Antimicrobial Traits of Tea- and Cranberry-Derived Polyphenols against Streptococcus mutans"},{"docid":"MED-3981","text":"The aim of this study was to investigate the relationship between child characteristics, parental and environmental factors and the occurrence of acute respiratory illness (ARI) and acute otitis media (AOM) among Finnish children attending day care centres (DCCs). The study was a cross-sectional questionnaire of 594 children aged 1-6 y from 18 DCCs in Helsinki, Finland. Recurrent (> or =4 diseases/y) ARI was present in 44% of the 1-3-y-olds and 23% of the 4-6-y-olds, and recurrent AOM in 15% and 2.5%, respectively. Parent atopic disease (odds ratio (OR) 1.53, p = 0.033), mother's academic education (OR 1.77, p = 0.008) and a medium length of DCC attendance compared to a short period (OR 1.67, p = 0.049) increased, while furry pets (OR 0.44, p = 0.003) and older child age (OR 0.38, p < 0.001) reduced the risk of recurrent ARI. Recurrent ARI (OR 3.96, p = 0.008), mother's academic education (OR 5.02, p = 0.003), and a medium length of DCC attendance compared to a short period (OR 3.34, p = 0.044) increased, while partial breastfeeding > or =6 months (OR 0.20, p = 0.002) and older child age (OR 0.05, p < 0.001) reduced the risk of recurrent AOM. Parental and environmental factors had a significant impact on recurrent ARI and AOM episodes in children attending DCCs. These risk factors should be considered in future studies intending to reduce DCC infections.","title":"Factors associated with acute respiratory illness in day care children."},{"docid":"MED-719","text":"In addition to causing embarrassment and unease, flatulence is linked to a variety of symptoms, some of which may be distressing. This review describes the origins of intestinal gas, its composition and methods which have been developed for its analysis. Emphasis is placed upon the effects of legumes in the diet in producing excessive intestinal gas and, particularly, on the role of raffinose-type oligosaccharides, containing alpha-galactosidic groupings. Suggestions for overcoming the problem are presented, including drug treatment, enzyme treatment, food processing and plant breeding. It is emphasised that removal of all raffinose-oligosaccharides from beans does not remove the problem of flatulence in animals and man; the compounds responsible--though assumed to be polysaccharides (or polysaccharide-derived oligomers formed by processing or cooking)--have yet to be characterised.","title":"Flatulence--causes, relation to diet and remedies."},{"docid":"MED-2272","text":"To assess the physiologic effects of cherry consumption, we measured plasma urate, antioxidant and inflammatory markers in 10 healthy women who consumed Bing sweet cherries. The women, age 22-40 y, consumed two servings (280 g) of cherries after an overnight fast. Blood and urine samples were taken before the cherry dose, and at 1.5, 3 and 5 h postdose. Plasma urate decreased 5 h postdose, mean +/- SEM = 183 +/- 15 micro mol/L compared with predose baseline of 214 +/- 13 micro mol/L (P < 0.05). Urinary urate increased postdose, with peak excretion of 350 +/- 33 micro mol/mmol creatinine 3 h postdose compared with 202 +/- 13 at baseline (P < 0.01). Plasma C-reactive protein (CRP) and nitric oxide (NO) concentrations had decreased marginally 3 h postdose (P < 0.1), whereas plasma albumin and tumor necrosis factor-alpha were unchanged. The vitamin C content of the cherries was solely as dehydroascorbic acid, but postdose increases in plasma ascorbic acid indicated that dehydroascorbic acid in fruits is bioavailable as vitamin C. The decrease in plasma urate after cherry consumption supports the reputed anti-gout efficacy of cherries. The trend toward decreased inflammatory indices (CRP and NO) adds to the in vitro evidence that compounds in cherries may inhibit inflammatory pathways.","title":"Consumption of cherries lowers plasma urate in healthy women."},{"docid":"MED-2117","text":"Recent evidence underlines the role of Western diet in the pathogenesis of acne. Acne is absent in populations consuming Palaeolithic diets with low glycaemic load and no consumption of milk or dairy products. Two randomized controlled studies, one of which is presented in this issue of Acta Dermato-Venereologica, have provided evidence for the beneficial therapeutic effects of low glycaemic load diets in acne. Epidemiological evidence confirms that milk consumption has an acne-promoting or acne-aggravating effect. Recent progress in understanding the nutrient-sensitive kinase mammalian target of rapamycin complex 1 (mTORC1) allows a new view of nutrient signalling in acne by both high glycaemic load and increased insulin-, IGF-1-, and leucine signalling due to milk protein consumption. Acne should be regarded as an mTORC1-driven disease of civilization, like obesity, type 2 diabetes and cancer induced by Western diet. Early dietary counselling of teenage acne patients is thus a great opportunity for dermatology, which will not only help to improve acne but may reduce the long-term adverse effects of Western diet on more serious mTORC1-driven diseases of civilization.","title":"Diet in acne: further evidence for the role of nutrient signalling in acne pathogenesis."}],"string":"[\n {\n \"docid\": \"MED-3840\",\n \"text\": \"The incidence of breast cancer is increasing in the Western world and there is an urgent need for studies of the mechanisms of sex steroids in order to develop novel preventive strategies. Diet modifications may be among the means for breast cancer prevention. Angiogenesis, key in tumor progression, is regulated by the balance between pro- and anti-angiogenic factors, which are controlled in the extracellular space. Sampling of these molecules at their bioactive compartment is therefore needed. The aims of this study were to explore if tamoxifen, one of the most used anti-estrogen treatments for breast cancer affected some of the most important endogenous angiogenesis regulators, vascular endothelial growth factor (VEGF), angiogenin, and endostatin in normal breast tissue in vivo and if a diet supplementation with flaxseed had similar effects as tamoxifen in the breast. Microdialysis was used for in situ sampling of extracellular proteins in normal breast tissue of women before and after six weeks of tamoxifen treatment or before and after addition of 25 g/day of ground flaxseed to the diet or in control women. We show significant correlations between estradiol and levels of VEGF, angiogenin, and endostatin in vivo, which was verified in ex vivo breast tissue culture. Moreover, tamoxifen decreased the levels of VEGF and angiogenin in the breast whereas endostatin increased significantly. Flaxseed did not alter VEGF or angiogenin levels but similar to tamoxifen the levels of endostatin increased significantly. We conclude that one of the mechanisms of tamoxifen in normal breast tissue include tipping of the angiogenic balance into an anti-angiogenic state and that flaxseed has limited effects on the pro-angiogenic factors whereas the anti-angiogenic endostatin may be modified by diet. Further studies of diet modifications for breast cancer prevention are warranted.\",\n \"title\": \"Tamoxifen and Flaxseed Alter Angiogenesis Regulators in Normal Human Breast Tissue In Vivo\"\n },\n {\n \"docid\": \"MED-4224\",\n \"text\": \"Metastatic, rather than primary tumours are responsible for ninety percent cancer deaths. Despite significant advances in the understanding of molecular and cellular mechanisms in tumour metastases, there are limitations in preventive treatment of metastatic tumours. Much evidence arising from laboratory and clinical studies suggests that growth factors and their receptors are implicated in cancer metastases development. We review the origin and production of growth factors and their receptors in all stages of cancer metastases including epithelial-mesenchymal transition, cancer cell invasion and migration, survival within the circulation, seeding at distant organs and metastatic tumour angiogenesis. The functions of growth factors and their receptors are also discussed. This review presents the efforts made in understanding this challenge to aid in the development of new treatment strategies for cancer metastases.\",\n \"title\": \"Growth Factors and their receptors in cancer metastases.\"\n },\n {\n \"docid\": \"MED-2818\",\n \"text\": \"Curcumin is a polyphenol derived from the herbal remedy and dietary spice turmeric. It possesses diverse anti-inflammatory and anti-cancer properties following oral or topical administration. Apart from curcumin's potent antioxidant capacity at neutral and acidic pH, its mechanisms of action include inhibition of several cell signalling pathways at multiple levels, effects on cellular enzymes such as cyclooxygenase and glutathione S-transferases, immuno-modulation and effects on angiogenesis and cell-cell adhesion. Curcumin's ability to affect gene transcription and to induce apoptosis in preclinical models is likely to be of particular relevance to cancer chemoprevention and chemotherapy in patients. Although curcumin's low systemic bioavailability following oral dosing may limit access of sufficient concentrations for pharmacological effect in certain tissues, the attainment of biologically active levels in the gastrointestinal tract has been demonstrated in animals and humans. Sufficient data currently exist to advocate phase II clinical evaluation of oral curcumin in patients with invasive malignancy or pre-invasive lesions of the gastrointestinal tract, particularly the colon and rectum.\",\n \"title\": \"Curcumin: the story so far.\"\n },\n {\n \"docid\": \"MED-2817\",\n \"text\": \"Curcumin (diferuloylmethane), a yellow coloring agent extracted from turmeric is also used as a remedy for the treatment and prevention of inflammatory diseases. Acute and chronic inflammation is a major factor in the progression of obesity, type II diabetes, arthritis, pancreatitis, cardiovascular, neurodegenerative and metabolic diseases, as well as certain types of cancer. Turmeric has a long history of use in Ayurvedic medicine for the treatment of inflammatory disorders. Recent studies on the efficacy and therapeutic applicability of turmeric have suggested that the active ingredient of tumeric is curcumin. Further, compelling evidence has shown that curcumin has the ability to inhibit inflammatory cell proliferation, invasion, and angiogenesis through multiple molecular targets and mechanisms of action. Curcumin is safe, non-toxic, and mediates its anti-inflammatory effects through the down-regulation of inflammatory transcription factors, cytokines, redox status, protein kinases, and enzymes that all promote inflammation. In addition, curcumin induces apoptosis through mitochondrial and receptor-mediated pathways, as well as activation of caspase cascades. In the current study, the anti-inflammatory effects of curcumin were evaluated relative to various chronic inflammatory diseases. Based on the available pharmacological data obtained from in vitro and in vivo research, as well as clinical trials, an opportunity exists to translate curcumin into clinics for the prevention of inflammatory diseases in the near future. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.\",\n \"title\": \"Curcumin in inflammatory diseases.\"\n },\n {\n \"docid\": \"MED-2507\",\n \"text\": \"Increased plasma levels of adiponectin, metformin therapy of diabetes, rapamycin administration in transplant patients, and lifelong consumption of low-protein plant-based diets have all been linked to decreased risk for various cancers. These benefits may be mediated, at least in part, by down-regulated activity of the mTORC1 complex, a key regulator of protein translation. By boosting the effective availability of the translation initiator eIF4E, mTORC1 activity promotes the translation of a number of \\\"weak\\\" mRNAs that code for proteins, often up-regulated in cancer, that promote cellular proliferation, invasiveness, and angiogenesis, and that abet cancer promotion and chemoresistance by opposing apoptosis. Measures which inhibit eIF4E activity, either directly or indirectly, may have utility not only for cancer prevention, but also for the treatment of many cancers in which eIF4E drives malignancy. Since eIF4E is overexpressed in many cancers, strategies which target eIF4E directly--some of which are now being assessed clinically--may have the broadest efficacy in this regard. Many of the \\\"weak\\\" mRNAs coding for proteins that promote malignant behavior or chemoresistance are regulated transcriptionally by NF-kappaB and/or Stat3, which are active in a high proportion of cancers; thus, regimens concurrently targeting eIF4E, NF-kappaB, and Stat3 may suppress these proteins at both the transcriptional and translational levels, potentially achieving a very marked reduction in their expression. Copyright © 2011 Elsevier Ltd. All rights reserved.\",\n \"title\": \"mTORC1 activity as a determinant of cancer risk--rationalizing the cancer-preventive effects of adiponectin, metformin, rapamycin, and low-protein ...\"\n },\n {\n \"docid\": \"MED-2824\",\n \"text\": \"Cancer is primarily a disease of old age, and that life style plays a major role in the development of most cancers is now well recognized. While plant-based formulations have been used to treat cancer for centuries, current treatments usually involve poisonous mustard gas, chemotherapy, radiation, and targeted therapies. While traditional plant-derived medicines are safe, what are the active principles in them and how do they mediate their effects against cancer is perhaps best illustrated by curcumin, a derivative of turmeric used for centuries to treat a wide variety of inflammatory conditions. Curcumin is a diferuloylmethane derived from the Indian spice, turmeric (popularly called \\\"curry powder\\\") that has been shown to interfere with multiple cell signaling pathways, including cell cycle (cyclin D1 and cyclin E), apoptosis (activation of caspases and down-regulation of antiapoptotic gene products), proliferation (HER-2, EGFR, and AP-1), survival (PI3K/AKT pathway), invasion (MMP-9 and adhesion molecules), angiogenesis (VEGF), metastasis (CXCR-4) and inflammation (NF-kappaB, TNF, IL-6, IL-1, COX-2, and 5-LOX). The activity of curcumin reported against leukemia and lymphoma, gastrointestinal cancers, genitourinary cancers, breast cancer, ovarian cancer, head and neck squamous cell carcinoma, lung cancer, melanoma, neurological cancers, and sarcoma reflects its ability to affect multiple targets. Thus an \\\"old-age\\\" disease such as cancer requires an \\\"age-old\\\" treatment.\",\n \"title\": \"Curcumin and cancer: an \\\"old-age\\\" disease with an \\\"age-old\\\" solution.\"\n },\n {\n \"docid\": \"MED-2922\",\n \"text\": \"Overwhelming evidence suggests that edible small and soft-fleshed berry fruits may have beneficial effects against several types of human cancers. The anticancer potential of berries has been related, at least in part, to a multitude of bioactive phytochemicals that these colorful fruits contain, including polyphenols (flavonoids, proanthocyanidins, ellagitannins, gallotannins, phenolic acids), stilbenoids, lignans, and triterpenoids. Studies show that the anticancer effects of berry bioactives are partially mediated through their abilities to counteract, reduce, and also repair damage resulting from oxidative stress and inflammation. In addition, berry bioactives also regulate carcinogen and xenobiotic metabolizing enzymes, various transcription and growth factors, inflammatory cytokines, and subcellular signaling pathways of cancer cell proliferation, apoptosis, and tumor angiogenesis. Berry phytochemicals may also potentially sensitize tumor cells to chemotherapeutic agents by inhibiting pathways that lead to treatment resistance, and berry fruit consumption may provide protection from therapy-associated toxicities. Although a wide variety of berry fruits are consumed worldwide, this paper focuses on those commonly consumed in North America, namely, blackberries, black raspberries, blueberries, cranberries, red raspberries, and strawberries. In addition, a large body of studies on singly purified berry bioactives is available, but this paper focuses on studies of \\\"whole berries\\\" per se, that is, as berry extracts and purified fractions, juices, and freeze-dried powders. Potential mechanisms of anticancer action and bioavailability of berry phenolics, as well as gaps in knowledge and recommendations for future berry research, are also briefly discussed.\",\n \"title\": \"Berry fruits for cancer prevention: current status and future prospects.\"\n },\n {\n \"docid\": \"MED-2357\",\n \"text\": \"Patients with cancer have circulating heterophile antibodies that agglutinate animal red cells via recognition of the mammalian cell surface sialic acid N-glycolylneuraminic acid (Neu5Gc), which was long considered an oncofetal antigen in humans. However, humans are genetically deficient in Neu5Gc production and instead metabolically accumulate Neu5Gc from dietary sources, particularly red meats and milk products. Moreover, mice with a human-like defect showed no alternate pathway for Neu5Gc synthesis and even normal humans express anti-Neu5Gc antibodies. We show here that human tumors accumulate Neu5Gc that is covalently attached to multiple classes of glycans. The paradox of human tumor Neu5Gc accumulation in the face of circulating anti-Neu5Gc antibodies was hypothesized to be due to facilitation of tumor progression by the resulting low-grade chronic inflammation. Indeed, murine tumors expressing human-like levels of Neu5Gc show accelerated growth in syngeneic mice with a human-like Neu5Gc deficiency, coincident with the induction of anti-Neu5Gc antibodies and increased infiltration of inflammatory cells. Transfer of polyclonal monospecific syngeneic mouse anti-Neu5Gc serum also enhanced growth of transplanted syngeneic tumors bearing human-like levels of Neu5Gc, with tumors showing evidence for antibody deposition, enhanced angiogenesis and chronic inflammation. These effects were suppressed by a cyclooxygenase-2 inhibitor, a drug type known to reduce human carcinoma risk. Finally, affinity-purified human anti-Neu5Gc antibodies also accelerate growth of Neu5Gc-containing tumors in Neu5Gc-deficient mice. Taken together, the data suggest that the human propensity to develop diet-related carcinomas is contributed to by local chronic inflammation, resulting from interaction of metabolically-accumulated dietary Neu5Gc with circulating anti-Neu5Gc antibodies.\",\n \"title\": \"Evidence for a human-specific mechanism for diet and antibody-mediated inflammation in carcinoma progression\"\n },\n {\n \"docid\": \"MED-3878\",\n \"text\": \"Diet, nutritional status, and certain dietary supplements are postulated to influence the development and progression of prostate cancer. Angiogenesis and inflammation are central to tumor growth and progression, but the effect of diet on these processes remains uncertain. We explored changes in 50 plasma cytokines and angiogenic factors (CAFs) in 145 men with prostate cancer enrolled in a pre-operative, randomized controlled phase-II trial with four arms: control (usual diet); low-fat (LF) diet; flaxseed-supplemented (FS) diet; and flaxseed-supplemented, low-fat diet. The mean duration of dietary intervention was 30–31 days. Among the individual arms, the largest number of significant changes (baseline vs pre-operative follow-up) was observed in the LF arm, with 19 CAFs decreasing and one increasing (p<.05). Compared to the control arm, 6 CAFs—including pro-angiogenic factors (stromal-cell derived-1α and myeloid factors (granulocyte-colony-stimulating factor, macrophage colony-stimulating factor — all decreased in the LF arm compared to controls; 3 and 4 CAFs changed in the FS and FS+LF arms, respectively. Weight loss occurred in the LF arms and significantly correlated with VEGF decreases (P <0.001). The CAFs that changed in the LF arm are all known to be regulated by nuclear factor-kappa B (NF-κB), and a pathway analysis identified NF-κB as the most likely regulatory network associated with these changes in the LF arm, but not in the FS-containing arms. These results suggest that a low-fat diet without flaxseed may reduce levels of specific inflammatory cytokines and angiogenic factors and suggests that the NF-κB pathway may be a mediator of these changes.\",\n \"title\": \"Effect of Low-fat Diets on Plasma Levels of NFκB-regulated Inflammatory Cytokines and Angiogenic Factors in Men with Prostate Cancer\"\n },\n {\n \"docid\": \"MED-3721\",\n \"text\": \"Reduced expression of proapoptotic and terminal differentiation genes in conjunction with increased levels of the proinflammatory and angiogenesis-inducing enzymes, cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS), correlate with malignant transformation of oral intraepithelial neoplasia (IEN). Accordingly, this study investigated the effects of a 10% (w/w) freeze-dried black raspberry gel on oral IEN histopathology, gene expression profiles, intraepithelial COX-2 and iNOS proteins, and microvascular densities. Our laboratories have shown that freeze-dried black raspberries possess antioxidant properties and also induce keratinocyte apoptosis and terminal differentiation. Oral IEN tissues were hemisected to provide samples for pretreatment diagnoses and establish baseline biochemical and molecular variables. Treatment of the remaining lesional tissue (0.5 g gel applied four times daily for 6 weeks) began 1 week after the initial biopsy. RNA was isolated from snap-frozen IEN lesions for microarray analyses, followed by quantitative reverse transcription-PCR validation. Additional epithelial gene-specific quantitative reverse transcription-PCR analyses facilitated the assessment of target tissue treatment effects. Surface epithelial COX-2 and iNOS protein levels and microvascular densities were determined by image analysis quantified immunohistochemistry. Topical berry gel application uniformly suppressed genes associated with RNA processing, growth factor recycling, and inhibition of apoptosis. Although the majority of participants showed posttreatment decreases in epithelial iNOS and COX-2 proteins, only COX-2 reductions were statistically significant. These data show that berry gel application modulated oral IEN gene expression profiles, ultimately reducing epithelial COX-2 protein. In a patient subset, berry gel application also reduced vascular densities in the superficial connective tissues and induced genes associated with keratinocyte terminal differentiation.\",\n \"title\": \"Topical Application of a Bioadhesive Black Raspberry Gel Modulates Gene Expression and Reduces Cyclooxygenase 2 Protein in Human Premalignant Oral Lesions\"\n },\n {\n \"docid\": \"MED-3702\",\n \"text\": \"BACKGROUND: Increased prevalence of allergic diseases in western societies has been described as an epidemic. The precise turning point for the epidemic and the antigens responsible for it remain obscure. OBJECTIVE: To evaluate how the prevalence of atopic disease has changed in terms of detectable sensitization to aeroallergens and dietary allergens in a cross-sectional comparison of subjects from birth cohorts more than 60 years apart. METHODS: We studied four groups of 100 subjects each (at ages 7, 27, 47 and 67 years), representing those born in 1990, 1963-66, 1943-46 and in 1923-26, respectively. Serum total and specific IgE concentrations against aeroallergens and dietary allergens were determined. A questionnaire elicited information on symptoms, allergic diseases and medication. RESULTS: The proportion of subjects with detectable IgE antibodies against aeroallergens increased consistently from the oldest to the youngest birth cohorts; chi2 trend=56.809, P<0.0001. Similar progression was not seen in sensitization to dietary allergens. The proportion of those with diagnosed asthma differed significantly (chi2=13.45, P=0.004) across the birth cohorts. The lowest prevalence of asthma and sensitization to dietary allergens was detected in those born in 1943-46, i.e. during or immediately after World War II. CONCLUSION: Prevalence of sensitization to airborne allergens, unlike that to dietary allergens, has increased over a long period of time. Our results support the concept of the immune function being programmed by external factors early in life. They also call for caution when interpretations of the pace and possible causes of the allergy epidemic are made on the basis of short-term studies.\",\n \"title\": \"The allergy epidemic extends beyond the past few decades.\"\n },\n {\n \"docid\": \"MED-3541\",\n \"text\": \"OBJECTIVE: The study evaluated the association between consumption frequencies of the major food categories and the risk of new depression four years later in older Taiwanese. DESIGN: A prospective cohort study with multistage random sampling. Logistic regression analysis evaluated the significance of the longitudinal associations of intake frequencies of the major food categories with future (4 years later) risk of new depression, controlled for possible confounding factors with or without adjustment for cognitive status. SETTING: Population-based free-living elderly. SUBJECTS: Men and women (n 1609) ≥65 years of age. RESULTS: In a regression model that controlled for demographic, socio-economic, lifestyle and disease/health-related variables but not cognitive status, both fruits (OR = 0·66, 95 % CI 0·45, 0·98, P = 0·038) and vegetables (OR = 0·38, 95 % CI 0·17, 0·86, P = 0·021) were protective against depressive symptoms 4 years later. However, when the same regression model was also adjusted for cognitive status, only vegetables (OR = 0·40, 95 % CI 0·17, 0·95, P = 0·039) were protective against depressive symptoms. Higher consumption of eggs was close to being significant in both regression models (P = 0·087 and 0·069, respectively). Other food categories including meat/poultry, fish, seafood, dairy, legumes, grains and tea showed no significant associations. CONCLUSIONS: Results suggest that although confounding factors cannot be totally ruled out, more frequent consumption of vegetables seems to be protective against depressive symptoms in the elderly. Further studies are needed to elucidate the causal role and the mechanism of the association.\",\n \"title\": \"Frequent consumption of vegetables predicts lower risk of depression in older Taiwanese - results of a prospective population-based study.\"\n },\n {\n \"docid\": \"MED-5122\",\n \"text\": \"BACKGROUND: Drinking mate has been associated with cancers of the esophagus, oropharynx, larynx, lung, kidney, and bladder. We conducted this study to determine whether drinking mate could lead to substantial exposure to polycyclic aromatic hydrocarbons (PAH), including known carcinogens, such as benzo[a]pyrene. METHODS: The concentrations of 21 individual PAHs were measured in dry leaves of eight commercial brands of yerba mate and in infusions made with hot (80 degrees C) or cold (5 degrees C) water. Measurements were done using gas chromatography/mass spectrometry, with deuterated PAHs as the surrogates. Infusions were made by adding water to the leaves, removing the resulting infusion after 5 min, and then adding more water to the remaining leaves. This process was repeated 12 times for each infusion temperature. RESULTS: The total concentrations of the 21 PAHs in different brands of yerba mate ranged from 536 to 2,906 ng/g dry leaves. Benzo[a]pyrene concentrations ranged from 8.03 to 53.3 ng/g dry leaves. For the mate infusions prepared using hot water and brand 1, 37% (1,092 of 2,906 ng) of the total measured PAHs and 50% (25.1 of 50 ng) of the benzo[a]pyrene content were released into the 12 infusions. Similar results were obtained for other hot and cold infusions. CONCLUSION: Very high concentrations of carcinogenic PAHs were found in yerba mate leaves and in hot and cold mate infusions. Our results support the hypothesis that the carcinogenicity of mate may be related to its PAH content.\",\n \"title\": \"High levels of carcinogenic polycyclic aromatic hydrocarbons in mate drinks.\"\n },\n {\n \"docid\": \"MED-4722\",\n \"text\": \"BACKGROUND: There has been a resurgence of interest in the controversial relation between dietary protein and bone health. OBJECTIVE: This article reports on the first systematic review and meta-analysis of the relation between protein and bone health in healthy human adults. DESIGN: The MEDLINE (January 1966 to September 2007) and EMBASE (1974 to July 2008) databases were electronically searched for all relevant studies of healthy adults; studies of calcium excretion or calcium balance were excluded. RESULTS: In cross-sectional surveys, all pooled r values for the relation between protein intake and bone mineral density (BMD) or bone mineral content at the main clinically relevant sites were significant and positive; protein intake explained 1-2% of BMD. A meta-analysis of randomized placebo-controlled trials indicated a significant positive influence of all protein supplementation on lumbar spine BMD but showed no association with relative risk of hip fractures. No significant effects were identified for soy protein or milk basic protein on lumbar spine BMD. CONCLUSIONS: A small positive effect of protein supplementation on lumbar spine BMD in randomized placebo-controlled trials supports the positive association between protein intake and bone health found in cross-sectional surveys. However, these results were not supported by cohort study findings for hip fracture risk. Any effects found were small and had 95% CIs that were close to zero. Therefore, there is a small benefit of protein on bone health, but the benefit may not necessarily translate into reduced fracture risk in the long term.\",\n \"title\": \"Dietary protein and bone health: a systematic review and meta-analysis.\"\n },\n {\n \"docid\": \"MED-1118\",\n \"text\": \"OBJECTIVE: To measure Proteus mirabilis and Escherichia coli antibody levels in patients with rheumatoid arthritis (RA) during treatment by vegetarian diet. METHODS: Sera were collected from 53 RA patients who took part in a controlled clinical trial of fasting and a one year vegetarian diet. P mirabilis and E coli antibody levels were measured by an indirect immunofluorescence technique and an enzyme immunoassay, respectively. RESULTS: The patients on the vegetarian diet had a significant reduction in the mean anti-proteus titres at all time points during the study, compared with baseline values (all p < 0.05). No significant change in titre was observed in patients who followed an omnivorous diet. The decrease in anti-proteus titre was greater in the patients who responded well to the vegetarian diet compared with diet non-responders and omnivores. The total IgG concentration and levels of antibody against E coli, however, were almost unchanged in all patient groups during the trial. The decrease from baseline in proteus antibody levels correlated significantly (p < 0.001) with the decrease in a modified Stoke disease activity index. CONCLUSION: The decrease in P mirabilis antibody levels in the diet responders and the correlation between the decrease in proteus antibody level and decrease in disease activity supports the suggestion of an aetiopathogenetic role for P mirabilis in RA.\",\n \"title\": \"Decrease in anti-Proteus mirabilis but not anti-Escherichia coli antibody levels in rheumatoid arthritis patients treated with fasting and a one year vegetarian diet.\"\n },\n {\n \"docid\": \"MED-3177\",\n \"text\": \"Neurocysticercosis (NCC) is an infection of the central nervous system (CNS) caused by the metacestode larval form of the parasite Taenia sp. Many factors can contribute to the endemic nature of cysticercosis. The inflammatory process that occurs in the tissue surrounding the parasite and/or distal from it can result from several associated mechanisms and may be disproportionate with the number of cysts. This discrepancy may lead to difficulty with the proper diagnosis in people from low endemic regions or regions that lack laboratory resources. In the CNS, the cysticerci have two basic forms, isolated cysts (Cysticercus cellulosae=CC) and racemose cysts (Cysticercus racemosus=CR), and may be meningeal, parenchymal, or ventricular or have a mixed location. The clinical manifestations are based on two fundamental syndromes that may occur in isolation or be associated: epilepsy and intracranial hypertension. They may be asymptomatic, symptomatic or fatal; have an acute, sub-acute or chronic picture; or may be in remission or exacerbated. The cerebrospinal fluid (CSF) may be normal, even in patients with viable cysticerci, until the patients begin to exhibit the classical syndrome of NCC in the CSF, or show changes in one or more routine analysed parameters. Computed tomography (CT) and magnetic resonance imaging (MRI) have allowed non-invasive diagnoses, but can lead to false negatives. Treatment is a highly controversial issue and is characterised by individualised therapy sessions. Two drugs are commonly used, praziquantel (PZQ) and albendazole (ABZ). The choice of anti-inflammatory drugs includes steroids and dextrochlorpheniramine (DCP). Hydrocephalus is a common secondary effect of NCC. Surgical cases of hydrocephalus must be submitted to ventricle-peritoneal shunt (VPS) immediately before cysticidal treatment, and surgical extirpation of the cyst may lead to an absence of the surrounding inflammatory process. The progression of NCC may be simple or complicated, have remission with or without treatment and may exhibit symptoms that can disappear for long periods of time or persist until death. Unknown, neglected and controversial aspects of NCC, such as the impaired fourth ventricle syndrome, the presence of chronic brain oedema and psychic complaints, in addition to the lack of detectable glucose in the CSF and re-infection are discussed.\",\n \"title\": \"Neurocysticercosis: the enigmatic disease.\"\n },\n {\n \"docid\": \"MED-4351\",\n \"text\": \"The past decade has seen an explosion in research focusing on innate immunity. Through a wide range of mechanisms including phagocytosis, intracellular killing, and activation of pro-inflammatory or antiviral cytokine production via pattern recognition receptors, the cells of the innate immune system initiate and support adaptive immunity. The effects of aging on innate immune responses remain incompletely understood, particularly in humans. Here, we review advances in the study of human immunosenescence in the diverse cells of the innate immune system, including neutrophils, monocytes, macrophages, NK and NKT cells, and dendritic cells—with a focus on consequences for the response to infection or vaccination in old age.\",\n \"title\": \"Human innate Immunosenescence: causes and consequences for immunity in old age\"\n },\n {\n \"docid\": \"MED-1038\",\n \"text\": \"We examined effects of fiber on stool output, since this is one of the primary mediating variables for the hypothesized relationship between fiber and disease. Total neutral detergent fiber in the dietary fiber source was predictive of stool weight but not frequency. Substantial individual differences in stool output remained when dietary factors were controlled. Personality measures were used to predict stool weight and frequency independently of diet, and accounted for about as much variance in stool output as did dietary fiber. These results suggest that personality factors predispose some persons to low stool output. These individuals may benefit particularly from dietary fiber.\",\n \"title\": \"Dietary fiber and personality factors as determinants of stool output.\"\n },\n {\n \"docid\": \"MED-983\",\n \"text\": \"BACKGROUND: Our goal was to forecast the global burden of Alzheimer's disease and evaluate the potential impact of interventions that delay disease onset or progression. METHODS: A stochastic, multistate model was used in conjunction with United Nations worldwide population forecasts and data from epidemiological studies of the risks of Alzheimer's disease. RESULTS: In 2006, the worldwide prevalence of Alzheimer's disease was 26.6 million. By 2050, the prevalence will quadruple, by which time 1 in 85 persons worldwide will be living with the disease. We estimate about 43% of prevalent cases need a high level of care, equivalent to that of a nursing home. If interventions could delay both disease onset and progression by a modest 1 year, there would be nearly 9.2 million fewer cases of the disease in 2050, with nearly the entire decline attributable to decreases in persons needing a high level of care. CONCLUSIONS: We face a looming global epidemic of Alzheimer's disease as the world's population ages. Modest advances in therapeutic and preventive strategies that lead to even small delays in the onset and progression of Alzheimer's disease can significantly reduce the global burden of this disease.\",\n \"title\": \"Forecasting the global burden of Alzheimer's disease.\"\n },\n {\n \"docid\": \"MED-2757\",\n \"text\": \"BACKGROUND: Multivitamins are the most commonly used supplement in the developed world. Recent epidemiologic findings suggest that multivitamin use increases the risk of mortality. OBJECTIVE: We aimed to determine whether multivitamin-multimineral treatment, used for primary or secondary prevention, increases the risk of mortality in independently living adults. DESIGN: We performed a meta-analysis of randomized controlled trials. Multiple electronic databases were systematically searched from March to October 2012. Randomized controlled primary or secondary prevention trials were considered for inclusion. Eligible trials investigated daily multivitamin-multimineral supplementation for ≥1 y. Cohorts described as institutionalized or as having terminal illness (tertiary prevention) were excluded. The number of deaths and the sample size of each study arm were extracted independently by 2 researchers. Twenty-one articles were included in the analysis, which generated a total pooled sample of 91,074 people and 8794 deaths. These trials were pooled in a meta-analysis, and the outcomes were expressed as RRs and 95% CIs. RESULTS: The average age of the pooled sample was 62 y, and the average duration of supplementation was 43 mo. Across all studies, no effect of multivitamin-multimineral treatment on all-cause mortality (RR: 0.98; 95% CI: 0.94, 1.02) was observed. There was a trend for a reduced risk of all-cause mortality across primary prevention trials (RR: 0.94; 95% CI: 0.89, 1.00). Multivitamin-multimineral treatment had no effect on mortality due to vascular causes (RR: 1.01; 95% CI: 0.93, 1.09) or cancer (RR: 0.96; 95% CI: 0.88, 1.04). No statistical evidence of heterogeneity or publication bias was observed. CONCLUSION: Multivitamin-multimineral treatment has no effect on mortality risk.\",\n \"title\": \"Multivitamin-multimineral supplementation and mortality: a meta-analysis of randomized controlled trials.\"\n },\n {\n \"docid\": \"MED-1200\",\n \"text\": \"Oxidative stress has been implicated in the pathophysiology of many neuropsychiatric disorders such as schizophrenia, bipolar disorder, major depression etc. Both genetic and nongenetic factors have been found to cause increased cellular levels of reactive oxygen species beyond the capacity of antioxidant defense mechanism in patients of psychiatric disorders. These factors trigger oxidative cellular damage to lipids, proteins and DNA, leading to abnormal neural growth and differentiation. Therefore, novel therapeutic strategies such as supplementation with antioxidants can be effective for long-term treatment management of neuropsychiatric disorders. The use of antioxidants and PUFAs as supplements in the treatment of neuropsychiatric disorders has provided some promising results. At the same time, one should be cautious with the use of antioxidants since excessive antioxidants could dangerously interfere with some of the protective functions of reactive oxygen species. The present article will give an overview of the potential strategies and outcomes of using antioxidants as therapeutics in psychiatric disorders.\",\n \"title\": \"Antioxidants as potential therapeutics for neuropsychiatric disorders\"\n },\n {\n \"docid\": \"MED-1131\",\n \"text\": \"To clarify the role of the faecal flora in the diet-induced decrease of rheumatoid arthritis (RA) activity, 43 RA patients were randomized into two groups: the test group to receive living food, a form of uncooked vegan diet rich in lactobacilli, and the control group to continue their ordinary omnivorous diets. Based on clinical assessments before, during and after the intervention period, a disease improvement index was constructed for each patient. According to the index, patients were assigned either to a group with a high improvement index (HI) or to a group with a low improvement index (LO). Stool samples collected from each patient before the intervention and at 1 month were analysed by direct stool sample gas-liquid chromatography of bacterial cellular fatty acids. This method has proved to be a simple and sensitive way to detect changes and differences in the faecal microbial flora between individual stool samples or groups of them. A significant, diet-induced change in the faecal flora (P = 0.001) was observed in the test group, but not in the control group. Further, in the test group, a significant (P = 0.001) difference was detected between the HI and LO categories at 1 month, but not in the pre-test samples. We conclude that a vegan diet changes the faecal microbial flora in RA patients, and changes in the faecal flora are associated with improvement in RA activity.\",\n \"title\": \"Faecal microbial flora and disease activity in rheumatoid arthritis during a vegan diet.\"\n },\n {\n \"docid\": \"MED-1786\",\n \"text\": \"Fertility status may predict later mortality, but no studies have examined the effect of semen quality on subsequent mortality. Men referred to the Copenhagen Sperm Analysis Laboratory by general practitioners and urologists from 1963 to 2001 were, through a unique personal identification number, linked to the Danish central registers that hold information on all cases of cancer, causes of death, and number of children in the Danish population. The men were followed until December 31, 2001, death, or censoring, whichever occurred first, and the total mortality and cause-specific mortality of the cohort were compared with those of all age-standardized Danish men or according to semen characteristics. Among 43,277 men without azospermia referred for infertility problems, mortality decreased as the sperm concentration increased up to a threshold of 40 million/mL. As the percentages of motile and morphologically normal spermatozoa and semen volume increased, mortality decreased in a dose-response manner (P(trend) < 0.05). The decrease in mortality among men with good semen quality was due to a decrease in a wide range of diseases and was found among men both with and without children; therefore, the decrease in mortality could not be attributed solely to lifestyle and/or social factors. Semen quality may therefore be a fundamental biomarker of overall male health.\",\n \"title\": \"Good semen quality and life expectancy: a cohort study of 43,277 men.\"\n },\n {\n \"docid\": \"MED-5361\",\n \"text\": \"OBJECTIVE: To compare 2 omega-3 (n-3) preparations enriched with eicosapentaenoic acid (EPA) versus docosahexaenoic acid (DHA) as monotherapy for major depressive disorder (MDD) in a 2-site, placebo-controlled, randomized, double-blind clinical trial. METHOD: 196 adults (53% female; mean [SD] age = 44.7 [13.4] years) with DSM-IV MDD and a baseline 17-item Hamilton Depression Rating Scale (HDRS-17) score ≥ 15 were randomized equally from May 18, 2006, to June 30, 2011, to 8 weeks of double-blind treatment with oral EPA-enriched n-3 1000 mg/d, DHA-enriched n-3 1,000 mg/d, or placebo. RESULTS: 154 subjects completed the study. Modified intent-to-treat (mITT) analysis (n = 177 subjects with ≥ 1 postbaseline visit; 59.3% female, mean [SD] age 45.8 [12.5] years) employed mixed-model repeated measures (MMRM). All 3 groups demonstrated statistically significant improvement in the HDRS-17 (primary outcome measure), 16-item Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR-16), and Clinical Global Improvement-Severity Scale (CGI-S) (P < .05), but neither n-3 preparation separated from placebo (P > .05). Response and remission rates were in the range of 40%-50% and 30%, respectively, for all treatments, with no significant differences between groups. One subject receiving EPA-enriched n-3 discontinued due to worsening depression, and 1 subject receiving placebo discontinued due to an unspecified \\\"negative reaction\\\" to pills. CONCLUSIONS: Neither EPA-enriched nor DHA-enriched n-3 was superior to placebo for the treatment of MDD. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00517036. © Copyright 2015 Physicians Postgraduate Press, Inc.\",\n \"title\": \"A double-blind, randomized controlled clinical trial comparing eicosapentaenoic acid versus docosahexaenoic acid for depression.\"\n },\n {\n \"docid\": \"MED-2658\",\n \"text\": \"The prevalence of allergic diseases has increased in recent decades. Allergic diseases, particularly asthma, are complex diseases with strong gene-environment interactions. Epidemiological studies have identified a variety of risk factors for the development of allergic diseases. Among them, endocrine-disrupting chemicals (EDCs) play an important role in triggering or exacerbating these diseases. 4-Nonylphenol (NP) and 4-octylphenol (OP)--two major alkylphenols--have been recognized as common toxic and xenobiotic endocrine disrupters. Due to their low solubility, high hydrophobicity, and low estrogenic activity, they tend to accumulate in the human body and may be associated with the adverse effects of allergic diseases. Recently, new evidence has supported the importance of alkylphenols in the in vitro allergic response. This review focuses on the effects of alkylphenols on several key cell types in the context of allergic inflammation. Copyright © 2012. Published by Elsevier B.V.\",\n \"title\": \"Alkylphenols--potential modulators of the allergic response.\"\n },\n {\n \"docid\": \"MED-3637\",\n \"text\": \"There are over 750 species of bacteria that inhabit the human oral cavity, but only a small fraction of those are attributed to causing plaque-related diseases such as caries. Streptococcus mutans is accepted as the main cariogenic agent and there is substantial knowledge regarding the specific virulence factors that render the organism a pathogen. There has been rising interest in alternative, target-specific treatment options as opposed to nonspecific mechanical plaque removal or application of broad-spectrum antibacterials that are currently in use. The impact of diet on oral health is undeniable, and this is directly observable in populations that consume high quantities of polyphenol-rich foods or beverages. Such populations have low caries incidence and better overall oral health. Camellia sinensis, the plant from which various forms of tea are derived, and Vaccinium macrocarpon (American cranberry fruit) have received notable attention both for their prevalence in the human diet as well as for their unique composition of polyphenols. The biologically active constituents of these plants have demonstrated potent enzyme-inhibitory properties without being bactericidal, a key quality that is important in developing therapies that will not cause microorganisms to develop resistance. The aim of this review is to consider studies that have investigated the feasibility of tea, cranberry, and other select plant derivatives as a potential basis for alternative therapeutic agents against Streptococcus mutans and to evaluate their current and future clinical relevance.\",\n \"title\": \"Antimicrobial Traits of Tea- and Cranberry-Derived Polyphenols against Streptococcus mutans\"\n },\n {\n \"docid\": \"MED-3981\",\n \"text\": \"The aim of this study was to investigate the relationship between child characteristics, parental and environmental factors and the occurrence of acute respiratory illness (ARI) and acute otitis media (AOM) among Finnish children attending day care centres (DCCs). The study was a cross-sectional questionnaire of 594 children aged 1-6 y from 18 DCCs in Helsinki, Finland. Recurrent (> or =4 diseases/y) ARI was present in 44% of the 1-3-y-olds and 23% of the 4-6-y-olds, and recurrent AOM in 15% and 2.5%, respectively. Parent atopic disease (odds ratio (OR) 1.53, p = 0.033), mother's academic education (OR 1.77, p = 0.008) and a medium length of DCC attendance compared to a short period (OR 1.67, p = 0.049) increased, while furry pets (OR 0.44, p = 0.003) and older child age (OR 0.38, p < 0.001) reduced the risk of recurrent ARI. Recurrent ARI (OR 3.96, p = 0.008), mother's academic education (OR 5.02, p = 0.003), and a medium length of DCC attendance compared to a short period (OR 3.34, p = 0.044) increased, while partial breastfeeding > or =6 months (OR 0.20, p = 0.002) and older child age (OR 0.05, p < 0.001) reduced the risk of recurrent AOM. Parental and environmental factors had a significant impact on recurrent ARI and AOM episodes in children attending DCCs. These risk factors should be considered in future studies intending to reduce DCC infections.\",\n \"title\": \"Factors associated with acute respiratory illness in day care children.\"\n },\n {\n \"docid\": \"MED-719\",\n \"text\": \"In addition to causing embarrassment and unease, flatulence is linked to a variety of symptoms, some of which may be distressing. This review describes the origins of intestinal gas, its composition and methods which have been developed for its analysis. Emphasis is placed upon the effects of legumes in the diet in producing excessive intestinal gas and, particularly, on the role of raffinose-type oligosaccharides, containing alpha-galactosidic groupings. Suggestions for overcoming the problem are presented, including drug treatment, enzyme treatment, food processing and plant breeding. It is emphasised that removal of all raffinose-oligosaccharides from beans does not remove the problem of flatulence in animals and man; the compounds responsible--though assumed to be polysaccharides (or polysaccharide-derived oligomers formed by processing or cooking)--have yet to be characterised.\",\n \"title\": \"Flatulence--causes, relation to diet and remedies.\"\n },\n {\n \"docid\": \"MED-2272\",\n \"text\": \"To assess the physiologic effects of cherry consumption, we measured plasma urate, antioxidant and inflammatory markers in 10 healthy women who consumed Bing sweet cherries. The women, age 22-40 y, consumed two servings (280 g) of cherries after an overnight fast. Blood and urine samples were taken before the cherry dose, and at 1.5, 3 and 5 h postdose. Plasma urate decreased 5 h postdose, mean +/- SEM = 183 +/- 15 micro mol/L compared with predose baseline of 214 +/- 13 micro mol/L (P < 0.05). Urinary urate increased postdose, with peak excretion of 350 +/- 33 micro mol/mmol creatinine 3 h postdose compared with 202 +/- 13 at baseline (P < 0.01). Plasma C-reactive protein (CRP) and nitric oxide (NO) concentrations had decreased marginally 3 h postdose (P < 0.1), whereas plasma albumin and tumor necrosis factor-alpha were unchanged. The vitamin C content of the cherries was solely as dehydroascorbic acid, but postdose increases in plasma ascorbic acid indicated that dehydroascorbic acid in fruits is bioavailable as vitamin C. The decrease in plasma urate after cherry consumption supports the reputed anti-gout efficacy of cherries. The trend toward decreased inflammatory indices (CRP and NO) adds to the in vitro evidence that compounds in cherries may inhibit inflammatory pathways.\",\n \"title\": \"Consumption of cherries lowers plasma urate in healthy women.\"\n },\n {\n \"docid\": \"MED-2117\",\n \"text\": \"Recent evidence underlines the role of Western diet in the pathogenesis of acne. Acne is absent in populations consuming Palaeolithic diets with low glycaemic load and no consumption of milk or dairy products. Two randomized controlled studies, one of which is presented in this issue of Acta Dermato-Venereologica, have provided evidence for the beneficial therapeutic effects of low glycaemic load diets in acne. Epidemiological evidence confirms that milk consumption has an acne-promoting or acne-aggravating effect. Recent progress in understanding the nutrient-sensitive kinase mammalian target of rapamycin complex 1 (mTORC1) allows a new view of nutrient signalling in acne by both high glycaemic load and increased insulin-, IGF-1-, and leucine signalling due to milk protein consumption. Acne should be regarded as an mTORC1-driven disease of civilization, like obesity, type 2 diabetes and cancer induced by Western diet. Early dietary counselling of teenage acne patients is thus a great opportunity for dermatology, which will not only help to improve acne but may reduce the long-term adverse effects of Western diet on more serious mTORC1-driven diseases of civilization.\",\n \"title\": \"Diet in acne: further evidence for the role of nutrient signalling in acne pathogenesis.\"\n }\n]"}}},{"rowIdx":186,"cells":{"query_id":{"kind":"string","value":"PLAIN-3369"},"query":{"kind":"string","value":"The Healthiest Beverage"},"positive_passages":{"kind":"list like","value":[{"docid":"MED-2827","text":"Alternative and complementary therapeutic approaches, such as the use of a wide array of herbal, nutritional, and physical manipulations, are becoming popular for relieving symptoms of osteoarthritis (OA). The present study evaluated the efficacy of soy protein (SP) supplementation in relieving the pain and discomfort associated with OA. One hundred and thirty-five free-living individuals (64 men and 71 women) with diagnosed OA or with self-reported chronic knee joint pain not attributed to injury or rheumatoid arthritis were recruited for this double-blind, placebo-controlled, parallel design study. Study participants were assigned randomly to consume 40 g of either supplemental SP or milk-based protein (MP) daily for 3 months. Pain, knee range of motion, and overall physical activity were evaluated prior to the start of treatment and monthly thereafter. Serum levels of glycoprotein 39 (YKL-40), a marker of cartilage degradation, and insulin-like growth factor-I (IGF-I), a growth factor associated with cartilage synthesis, were assessed at baseline and at the end of the study. Overall, SP improved OA-associated symptoms such as range of motion and several factors associated with pain and quality of life in comparison to MP. However, these beneficial effects were mainly due to the effect of SP in men rather than women. Biochemical markers of cartilage metabolism further support the efficacy of SP in men as indicated by a significant increase in serum level of IGF-I and a significant decrease in serum level of YKL-40 compared to MP. This study is the first to provide evidence of possible beneficial effects of SP in the management of OA. Examining and verifying the long-term effects of SP on improving symptoms of OA, particularly in men, is warranted.","title":"Soy protein may alleviate osteoarthritis symptoms."},{"docid":"MED-5052","text":"OBJECTIVE: Habitual green tea consumption has long been associated with health benefits including chemoprevention and cardiovascular protection. This non-systematic literature review presents the clinical evidence to date. METHOD: A literature review of peer-reviewed articles on observational and interventional studies was conducted to include green tea, its extract or its purified polyphenol (-)-epigallocatechin-3-gallate (EGCG). Electronic databases searched included PubMed (1966-2009) and the Cochrane Library (Issue 4, 2008). RESULTS: Observational studies are inconclusive on the benefits of habitual consumption of green tea in the prevention of most cancers. However, there are trends towards prevention in breast and prostate cancers. Interventional studies have demonstrated reduction in relapses following surgical resection in colorectal adenomas and increased survival rates in epithelial ovarian cancer. Observational studies indicate that green tea may provide protection against hypertension and reduce the risk for stroke, and interventional studies are providing biochemical and physiological evidence. CONCLUSION: Although the overall clinical evidence is inconclusive, habitual green tea consumption may be providing some level of chemoprevention in prostate and breast cancer. Green tea may also attenuate the risk factors association with the development of atherosclerosis thus reducing the incidence of cardiovascular events and stoke.","title":"Can green tea do that? A literature review of the clinical evidence."},{"docid":"MED-2826","text":"Background Curcumin extracts of turmeric are proposed to produce health benefits. To date, human intervention studies have focused mainly on people with existing health problems given high doses of poorly absorbed curcumin. The purpose of the current study was to check whether in healthy people, a low dose of a lipidated curcumin extract could alter wellness-related measures. Methods The present study was conducted in healthy middle aged people (40–60 years old) with a low dose of curcumin (80 mg/day) in a lipidated form expected to have good absorption. Subjects were given either curcumin (N = 19) or placebo (N = 19) for 4 wk. Blood and saliva samples were taken before and after the 4 weeks and analyzed for a variety of blood and saliva measures relevant to health promotion. Results Curcumin, but not placebo, produced the following statistically significant changes: lowering of plasma triglyceride values, lowering of salivary amylase levels, raising of salivary radical scavenging capacities, raising of plasma catalase activities, lowering of plasma beta amyloid protein concentrations, lowering of plasma sICAM readings, increased plasma myeloperoxidase without increased c-reactive protein levels, increased plasma nitric oxide, and decreased plasma alanine amino transferase activities. Conclusion Collectively, these results demonstrate that a low dose of a curcumin-lipid preparation can produce a variety of potentially health promoting effects in healthy middle aged people.","title":"Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people"},{"docid":"MED-2830","text":"OBJECTIVE: The aim of this work was to determine the bioavailability of herbs and spices after human consumption by measuring the ability to protect lymphocytes from an oxidative injury and by examining the impact on inflammatory biomarkers in activated THP-1 cells. METHODS: Ten to 12 subjects in each of 13 groups consumed a defined amount of herb or spice for 7 days. Blood was drawn from subjects before consumption and 1 hour after taking the final herb or spice capsules. Subject serum and various extractions of the herbs and spices were analyzed for antioxidant capacity by oxygen radical absorbance capacity (ORAC) analysis or by 1,1-diphenyl-2-picrylhydrzyl (DPPH). Subject peripheral blood mononuclear cells (PBMCs) in medium with10% autologous serum were incubated with hydrogen peroxide to induce DNA strand breaks. Subject serum was also used to treat activated THP-1 cells to determine relative quantities of 3 inflammatory cytokine (tumor necrosis factor-α [TNF-α], interleukin-1α [IL-1α], and IL-6) mRNAs. RESULTS: Herbs and spices that protected PBMCs against DNA strand breaks were paprika, rosemary, ginger, heat-treated turmeric, sage, and cumin. Paprika also appeared to protect cells from normal apoptotic processes. Of the 3 cytokine mRNAs studied (TNF-α, IL-1α, and IL-6), TNF-α was the most sensitive responder to oxidized LDL-treated macrophages. Clove, ginger, rosemary, and turmeric were able to significantly reduce oxidized LDL-induced expression of TNF-α. Serum from those consuming ginger reduced all three inflammatory biomarkers. Ginger, rosemary, and turmeric showed protective capacity by both oxidative protection and inflammation measures. CONCLUSIONS: DNA strand breaks and inflammatory biomarkers are a good functional measure of a food's bioavailability.","title":"Bioavailability of herbs and spices in humans as determined by ex vivo inflammatory suppression and DNA strand breaks."},{"docid":"MED-2831","text":"TNFs are major mediators of inflammation and inflammation-related diseases, hence, the United States Food and Drug Administration (FDA) has approved the use of blockers of the cytokine, TNF-α, for the treatment of osteoarthritis, inflammatory bowel disease, psoriasis and ankylosis. These drugs include the chimeric TNF antibody (infliximab), humanized TNF-α antibody (Humira) and soluble TNF receptor-II (Enbrel) and are associated with a total cumulative market value of more than $20 billion a year. As well as being expensive ($15 000–20 000 per person per year), these drugs have to be injected and have enough adverse effects to be given a black label warning by the FDA. In the current report, we describe an alternative, curcumin (diferuloylmethane), a component of turmeric (Curcuma longa) that is very inexpensive, orally bioavailable and highly safe in humans, yet can block TNF-α action and production in in vitro models, in animal models and in humans. In addition, we provide evidence for curcumin's activities against all of the diseases for which TNF blockers are currently being used. Mechanisms by which curcumin inhibits the production and the cell signalling pathways activated by this cytokine are also discussed. With health-care costs and safety being major issues today, this golden spice may help provide the solution. Linked Articles This article is part of a themed section on Emerging Therapeutic Aspects in Oncology. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.169.issue-8","title":"Curcumin: an orally bioavailable blocker of TNF and other pro-inflammatory biomarkers"}],"string":"[\n {\n \"docid\": \"MED-2827\",\n \"text\": \"Alternative and complementary therapeutic approaches, such as the use of a wide array of herbal, nutritional, and physical manipulations, are becoming popular for relieving symptoms of osteoarthritis (OA). The present study evaluated the efficacy of soy protein (SP) supplementation in relieving the pain and discomfort associated with OA. One hundred and thirty-five free-living individuals (64 men and 71 women) with diagnosed OA or with self-reported chronic knee joint pain not attributed to injury or rheumatoid arthritis were recruited for this double-blind, placebo-controlled, parallel design study. Study participants were assigned randomly to consume 40 g of either supplemental SP or milk-based protein (MP) daily for 3 months. Pain, knee range of motion, and overall physical activity were evaluated prior to the start of treatment and monthly thereafter. Serum levels of glycoprotein 39 (YKL-40), a marker of cartilage degradation, and insulin-like growth factor-I (IGF-I), a growth factor associated with cartilage synthesis, were assessed at baseline and at the end of the study. Overall, SP improved OA-associated symptoms such as range of motion and several factors associated with pain and quality of life in comparison to MP. However, these beneficial effects were mainly due to the effect of SP in men rather than women. Biochemical markers of cartilage metabolism further support the efficacy of SP in men as indicated by a significant increase in serum level of IGF-I and a significant decrease in serum level of YKL-40 compared to MP. This study is the first to provide evidence of possible beneficial effects of SP in the management of OA. Examining and verifying the long-term effects of SP on improving symptoms of OA, particularly in men, is warranted.\",\n \"title\": \"Soy protein may alleviate osteoarthritis symptoms.\"\n },\n {\n \"docid\": \"MED-5052\",\n \"text\": \"OBJECTIVE: Habitual green tea consumption has long been associated with health benefits including chemoprevention and cardiovascular protection. This non-systematic literature review presents the clinical evidence to date. METHOD: A literature review of peer-reviewed articles on observational and interventional studies was conducted to include green tea, its extract or its purified polyphenol (-)-epigallocatechin-3-gallate (EGCG). Electronic databases searched included PubMed (1966-2009) and the Cochrane Library (Issue 4, 2008). RESULTS: Observational studies are inconclusive on the benefits of habitual consumption of green tea in the prevention of most cancers. However, there are trends towards prevention in breast and prostate cancers. Interventional studies have demonstrated reduction in relapses following surgical resection in colorectal adenomas and increased survival rates in epithelial ovarian cancer. Observational studies indicate that green tea may provide protection against hypertension and reduce the risk for stroke, and interventional studies are providing biochemical and physiological evidence. CONCLUSION: Although the overall clinical evidence is inconclusive, habitual green tea consumption may be providing some level of chemoprevention in prostate and breast cancer. Green tea may also attenuate the risk factors association with the development of atherosclerosis thus reducing the incidence of cardiovascular events and stoke.\",\n \"title\": \"Can green tea do that? A literature review of the clinical evidence.\"\n },\n {\n \"docid\": \"MED-2826\",\n \"text\": \"Background Curcumin extracts of turmeric are proposed to produce health benefits. To date, human intervention studies have focused mainly on people with existing health problems given high doses of poorly absorbed curcumin. The purpose of the current study was to check whether in healthy people, a low dose of a lipidated curcumin extract could alter wellness-related measures. Methods The present study was conducted in healthy middle aged people (40–60 years old) with a low dose of curcumin (80 mg/day) in a lipidated form expected to have good absorption. Subjects were given either curcumin (N = 19) or placebo (N = 19) for 4 wk. Blood and saliva samples were taken before and after the 4 weeks and analyzed for a variety of blood and saliva measures relevant to health promotion. Results Curcumin, but not placebo, produced the following statistically significant changes: lowering of plasma triglyceride values, lowering of salivary amylase levels, raising of salivary radical scavenging capacities, raising of plasma catalase activities, lowering of plasma beta amyloid protein concentrations, lowering of plasma sICAM readings, increased plasma myeloperoxidase without increased c-reactive protein levels, increased plasma nitric oxide, and decreased plasma alanine amino transferase activities. Conclusion Collectively, these results demonstrate that a low dose of a curcumin-lipid preparation can produce a variety of potentially health promoting effects in healthy middle aged people.\",\n \"title\": \"Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people\"\n },\n {\n \"docid\": \"MED-2830\",\n \"text\": \"OBJECTIVE: The aim of this work was to determine the bioavailability of herbs and spices after human consumption by measuring the ability to protect lymphocytes from an oxidative injury and by examining the impact on inflammatory biomarkers in activated THP-1 cells. METHODS: Ten to 12 subjects in each of 13 groups consumed a defined amount of herb or spice for 7 days. Blood was drawn from subjects before consumption and 1 hour after taking the final herb or spice capsules. Subject serum and various extractions of the herbs and spices were analyzed for antioxidant capacity by oxygen radical absorbance capacity (ORAC) analysis or by 1,1-diphenyl-2-picrylhydrzyl (DPPH). Subject peripheral blood mononuclear cells (PBMCs) in medium with10% autologous serum were incubated with hydrogen peroxide to induce DNA strand breaks. Subject serum was also used to treat activated THP-1 cells to determine relative quantities of 3 inflammatory cytokine (tumor necrosis factor-α [TNF-α], interleukin-1α [IL-1α], and IL-6) mRNAs. RESULTS: Herbs and spices that protected PBMCs against DNA strand breaks were paprika, rosemary, ginger, heat-treated turmeric, sage, and cumin. Paprika also appeared to protect cells from normal apoptotic processes. Of the 3 cytokine mRNAs studied (TNF-α, IL-1α, and IL-6), TNF-α was the most sensitive responder to oxidized LDL-treated macrophages. Clove, ginger, rosemary, and turmeric were able to significantly reduce oxidized LDL-induced expression of TNF-α. Serum from those consuming ginger reduced all three inflammatory biomarkers. Ginger, rosemary, and turmeric showed protective capacity by both oxidative protection and inflammation measures. CONCLUSIONS: DNA strand breaks and inflammatory biomarkers are a good functional measure of a food's bioavailability.\",\n \"title\": \"Bioavailability of herbs and spices in humans as determined by ex vivo inflammatory suppression and DNA strand breaks.\"\n },\n {\n \"docid\": \"MED-2831\",\n \"text\": \"TNFs are major mediators of inflammation and inflammation-related diseases, hence, the United States Food and Drug Administration (FDA) has approved the use of blockers of the cytokine, TNF-α, for the treatment of osteoarthritis, inflammatory bowel disease, psoriasis and ankylosis. These drugs include the chimeric TNF antibody (infliximab), humanized TNF-α antibody (Humira) and soluble TNF receptor-II (Enbrel) and are associated with a total cumulative market value of more than $20 billion a year. As well as being expensive ($15 000–20 000 per person per year), these drugs have to be injected and have enough adverse effects to be given a black label warning by the FDA. In the current report, we describe an alternative, curcumin (diferuloylmethane), a component of turmeric (Curcuma longa) that is very inexpensive, orally bioavailable and highly safe in humans, yet can block TNF-α action and production in in vitro models, in animal models and in humans. In addition, we provide evidence for curcumin's activities against all of the diseases for which TNF blockers are currently being used. Mechanisms by which curcumin inhibits the production and the cell signalling pathways activated by this cytokine are also discussed. With health-care costs and safety being major issues today, this golden spice may help provide the solution. Linked Articles This article is part of a themed section on Emerging Therapeutic Aspects in Oncology. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.169.issue-8\",\n \"title\": \"Curcumin: an orally bioavailable blocker of TNF and other pro-inflammatory biomarkers\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"MED-4994","text":"BACKGROUND: The cardioprotective properties of moderate alcohol consumption, compared with abstinence or heavy drinking, are widely reported, but whether the benefits are experienced equally by all moderate drinkers is less well known. AIMS: To examine the association between average alcohol intake per week and the incidence of fatal and non-fatal myocardial infarction during 17 years of follow-up for 9655 men and women without prevalent disease in the general population; and to test whether the level of cardioprotection differs according to subjects' other health behaviours (healthy, moderately healthy, unhealthy) at entry to the study. METHOD: A longitudinal, British civil service-based cohort study, baseline in 1985-8. RESULTS: A significant benefit of moderate drinking compared with abstinence or heavy drinking was found among those with poor health behaviours (little exercise, poor diet and smokers). No additional benefit from alcohol was found among those with the healthiest behaviour profile (> or =3 hours of vigorous exercise per week, daily fruit or vegetable consumption and non-smokers). CONCLUSION: The cardioprotective benefit from moderate drinking does not apply equally to all drinkers, and this variability should be emphasised in public health messages.","title":"Who benefits most from the cardioprotective properties of alcohol consumption--health freaks or couch potatoes?"},{"docid":"MED-1743","text":"This article describes the nutrient and elemental composition, including residues of herbicides and pesticides, of 31 soybean batches from Iowa, USA. The soy samples were grouped into three different categories: (i) genetically modified, glyphosate-tolerant soy (GM-soy); (ii) unmodified soy cultivated using a conventional \"chemical\" cultivation regime; and (iii) unmodified soy cultivated using an organic cultivation regime. Organic soybeans showed the healthiest nutritional profile with more sugars, such as glucose, fructose, sucrose and maltose, significantly more total protein, zinc and less fibre than both conventional and GM-soy. Organic soybeans also contained less total saturated fat and total omega-6 fatty acids than both conventional and GM-soy. GM-soy contained high residues of glyphosate and AMPA (mean 3.3 and 5.7 mg/kg, respectively). Conventional and organic soybean batches contained none of these agrochemicals. Using 35 different nutritional and elemental variables to characterise each soy sample, we were able to discriminate GM, conventional and organic soybeans without exception, demonstrating \"substantial non-equivalence\" in compositional characteristics for 'ready-to-market' soybeans. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.","title":"Compositional differences in soybeans on the market: glyphosate accumulates in Roundup Ready GM soybeans."},{"docid":"MED-1646","text":"The Beverage Guidance Panel was assembled to provide guidance on the relative health and nutritional benefits and risks of various beverage categories. The beverage panel was initiated by the first author. The Panel's purpose is to attempt to systematically review the literature on beverages and health and provide guidance to the consumer. An additional purpose of the Panel is to develop a deeper dialog among the scientific community on overall beverage consumption patterns in the United States and on the great potential to change this pattern as a way to improve health. Over the past several decades, levels of overweight and obesity have increased across all population groups in the United States. Concurrently, an increased daily intake of 150-300 kcal (for different age-sex groups) has occurred, with approximately 50% of the increased calories coming from the consumption of calorically sweetened beverages. The panel ranked beverages from the lowest to the highest value based on caloric and nutrient contents and related health benefits and risks. Drinking water was ranked as the preferred beverage to fulfill daily water needs and was followed in decreasing value by tea and coffee, low-fat (1.5% or 1%) and skim (nonfat) milk and soy beverages, noncalorically sweetened beverages, beverages with some nutritional benefits (fruit and vegetable juices, whole milk, alcohol, and sports drinks), and calorically sweetened, nutrient-poor beverages. The Panel recommends that the consumption of beverages with no or few calories should take precedence over the consumption of beverages with more calories.","title":"A new proposed guidance system for beverage consumption in the United States."},{"docid":"MED-1710","text":"Sugar intake in the United States has increased by >40 fold since the American Revolution. The health concerns that have been raised about the amounts of sugar that are in the current diet, primarily as beverages, are the subject of this review. Just less than 50% of the added sugars (sugar and high-fructose corn syrup) are found in soft drinks and fruit drinks. The intake of soft drinks has increased 5-fold between 1950 and 2000. Most meta-analyses have shown that the risk of obesity, diabetes, cardiovascular disease, and metabolic syndrome are related to consumption of beverages sweetened with sugar or high-fructose corn syrup. Calorically sweetened beverage intake has also been related to the risk of nonalcoholic fatty liver disease, and, in men, gout. Calorically sweetened beverages contribute to obesity through their caloric load, and the intake of beverages does not produce a corresponding reduction in the intake of other food, suggesting that beverage calories are “add-on” calories. The increase in plasma triglyceride concentrations by sugar-sweetened beverages can be attributed to fructose rather than glucose in sugar. Several randomized trials of sugar-containing soft drinks versus low-calorie or calorie-free beverages show that either sugar, 50% of which is fructose, or fructose alone increases triglycerides, body weight, visceral adipose tissue, muscle fat, and liver fat. Fructose is metabolized primarily in the liver. When it is taken up by the liver, ATP decreases rapidly as the phosphate is transferred to fructose in a form that makes it easy to convert to lipid precursors. Fructose intake enhances lipogenesis and the production of uric acid. By worsening blood lipids, contributing to obesity, diabetes, fatty liver, and gout, fructose in the amounts currently consumed is hazardous to the health of some people.","title":"Energy and Fructose From Beverages Sweetened With Sugar or High-Fructose Corn Syrup Pose a Health Risk for Some People"},{"docid":"MED-1858","text":"As a hard tissue dental disease, dental erosion has a multifactorial etiology. The majority of dental erosion that originates from extrinsic sources is the result of dietary intake, particularly acidic beverages. Several preventive means have been proposed to minimize the damage to the dentition, including a reduction in the consumption of causative beverages and the adoption of a specific method of drinking, utilizing a straw instead of a cup. This article presents two cases involving the clinical and radiographic features of erosion lesions associated with chronic and excessive intake of acidic carbonated beverages. These examples embody how drinking patterns influence the formation of erosion lesions in various anatomic locations within the dentition. The clinical and radiographic evidence presented in this report cautions against the use of nonspecific terms, such as \"cup versus straw,\" and instead suggests implementing a more precise description of the suggested method. In view of the extensive damage inflicted by the chronic, excessive intake of carbonated beverages, preventive measures are considered to be the only effective course of management. This article offers illustrative examples of erosion lesions associated with long-term excessive intake of carbonated beverages. The influence of the drinking method--that is, a straw positioned into the labial vestibule versus a cup--on the anatomic location of the erosion lesions will be demonstrated through clinical and radiographic evidence.","title":"Influence of drinking patterns of carbonated beverages on dental erosion."},{"docid":"MED-713","text":"The effect of beverages prepared from the dried calyx of the flowers of Hibiscus sabdariffa on the excretion of diclofenac was investigated using a controlled study in healthy human volunteers. A high pressure liquid chromatographic method was used to analyse the 8 h urine samples collected after the administration of diclofenac with 300 mL (equivalent to 8.18 mg anthocyanins) of the beverage administered daily for 3 days. An unpaired two-tailed t-test was used to analyse for significant difference observed in the amount of diclofenac excreted before and after administration of the beverage. There was a reduction in the amount of diclofenac excreted and the wide variability observed in the control with the water beverage of Hibiscus sabdariffa (p < 0.05). There is an increasing need to counsel patients against the use of plant beverages with drugs.","title":"Effects of water extract of Hibiscus sabdariffa, Linn (Malvaceae) 'Roselle' on excretion of a diclofenac formulation."},{"docid":"MED-1627","text":"Sweetened beverages, coffee, and tea are the most consumed non-alcoholic beverages and may have important health consequences. We prospectively evaluated the consumption of various types of beverages assessed in 1995–1996 in relation to self-reported depression diagnosis after 2000 among 263,923 participants of the NIH-AARP Diet and Health Study. Odds ratios (OR) and 95% confidence intervals (CI) were derived from multivariate logistic regressions. The OR (95% CI) comparing ≥4 cans/cups per day with none were 1.30 (95%CI: 1.17–1.44) for soft drinks, 1.38 (1.15–1.65) for fruit drinks, and 0.91 (0.84–0.98) for coffee (all P for trend<0.0001). Null associations were observed for iced-tea and hot tea. In stratified analyses by drinkers of primarily diet versus regular beverages, the ORs were 1.31 (1.16–1.47) for diet versus 1.22 (1.03–1.45) for regular soft drinks, 1.51 (1.18–1.92) for diet versus 1.08 (0.79–1.46) for regular fruit drinks, and 1.25 (1.10–1.41) for diet versus 0.94 (0.83–1.08) for regular sweetened iced-tea. Finally, compared to nondrinkers, drinking coffee or tea without any sweetener was associated with a lower risk for depression, adding artificial sweeteners, but not sugar or honey, was associated with higher risks. Frequent consumption of sweetened beverages, especially diet drinks, may increase depression risk among older adults, whereas coffee consumption may lower the risk.","title":"Sweetened Beverages, Coffee, and Tea and Depression Risk among Older US Adults"},{"docid":"MED-897","text":"The effects of different polyphenol-containing beverages on Fe absorption from a bread meal were estimated in adult human subjects from the erythrocyte incorporation of radio-Fe. The test beverages contained different polyphenol structures and were rich in either phenolic acids (chlorogenic acid in coffee), monomeric flavonoids (herb teas, camomile (Matricaria recutita L.), vervain (Verbena officinalis L.), lime flower (Tilia cordata Mill.), pennyroyal (Mentha pulegium L.) and peppermint (Mentha piperita L.), or complex polyphenol polymerization products (black tea and cocoa). All beverages were potent inhibitors of Fe absorption and reduced absorption in a dose-dependent fashion depending on the content of total polyphenols. Compared with a water control meal, beverages containing 20-50 mg total polyphenols/serving reduced Fe absorption from the bread meal by 50-70%, whereas beverages containing 100-400 mg total polyphenols/serving reduced Fe absorption by 60-90%. Inhibition by black tea was 79-94%, peppermint tea 84%, pennyroyal 73%, cocoa 71%, vervain 59%, lime flower 52% and camomile 47%. At an identical concentration of total polyphenols, black tea was more inhibitory than cocoa, and more inhibitory than herb teas camomile, vervain, lime flower and pennyroyal, but was of equal inhibition to peppermint tea. Adding milk to coffee and tea had little or no influence on their inhibitory nature. Our findings demonstrate that herb teas, as well as black tea, coffee and coca can be potent inhibitors of Fe absorption. This property should be considered when giving dietary advice in relation to Fe nutrition.","title":"Inhibition of non-haem iron absorption in man by polyphenolic-containing beverages."},{"docid":"MED-3763","text":"The aim of this study was to explore oral exposure to carcinogenic (group 1) acetaldehyde after single sips of strong alcoholic beverages containing no or high concentrations of acetaldehyde. Eight volunteers tasted 5 ml of ethanol diluted to 40 vol.% with no acetaldehyde and 40 vol.% calvados containing 2400 μM acetaldehyde. Salivary acetaldehyde and ethanol concentrations were measured by gas chromatography. The protocol was repeated after ingestion of ethanol (0.5 g/kg body weight). Salivary acetaldehyde concentration was significantly higher after sipping calvados than after sipping ethanol at 30s both with (215 vs. 128 μmol/l, p<0.05) and without (258 vs. 89 μmol/l, p<0.05) alcohol ingestion. From 2 min onwards there were no significant differences in the decreasing salivary acetaldehyde concentration, which remained above the level of carcinogenicity still at 10 min. The systemic alcohol distribution from blood to saliva had no additional effect on salivary acetaldehyde after sipping of the alcoholic beverages. Carcinogenic concentrations of acetaldehyde are produced from ethanol in the oral cavity instantly after a small sip of strong alcoholic beverage, and the exposure continues for at least 10 min. Acetaldehyde present in the beverage has a short-term effect on total acetaldehyde exposure. Copyright © 2011 Elsevier Ltd. All rights reserved.","title":"A single sip of a strong alcoholic beverage causes exposure to carcinogenic concentrations of acetaldehyde in the oral cavity."},{"docid":"MED-918","text":"Consumption of a large amount of dietary fructose induces gastrointestinal intolerance, and glucose has been known as an enhancer of fructose absorption. Erythritol is a nonglycemic sugar alcohol, and it has been suggested that erythritol is absorbed paracellularly. It was hypothesized that paracellular absorption of erythritol could also enhance paracellular absorption of fructose in healthy adults. This is one of the proposed pathways for how additional glucose enhances the absorption of fructose. Thirty-seven nondiabetic, healthy adults participated in a randomized, double-masked, controlled crossover study. After an overnight fast, participants consumed beverages containing either 50 g fructose and 50 g glucose, 50 g fructose and 33.3 g erythritol (an equimolar concentration of fructose), or 50 g fructose alone. Breath hydrogen response was determined for 8 hours postprandially. Gastrointestinal intolerance symptoms and the number and consistency of bowel movements were recorded for 24 hours postprandially. The breath hydrogen area under the curve (AUC) of the fructose and erythritol beverage was 2 times the AUC of the fructose beverage and 8.75 times the AUC of the fructose and glucose beverage (P < .001, respectively). Compared with fructose and glucose beverage and fructose alone, frequency of watery stools increased (P < .05) and gastrointestinal tolerance worsened (P < .05) when participants consumed fructose and erythritol. These data suggest that coingestion of equimolar concentrations of fructose and erythritol increased carbohydrate malabsorption. Copyright © 2011 Elsevier Inc. All rights reserved.","title":"Combination of erythritol and fructose increases gastrointestinal symptoms in healthy adults."},{"docid":"MED-1637","text":"Epidemiologic studies suggest that tea consumption decreases the risk for cardiovascular events. However, there has been no clinical report examining the effects of tea consumption on coronary circulation. The purpose of this study was to evaluate the effects of black tea on coronary flow velocity reserve (CFVR) using transthoracic Doppler echocardiography (TTDE). This was a double-blind crossover study of 10 healthy male volunteers conducted to compare the effects of black tea and caffeine on coronary circulation. The coronary flow velocity of the left anterior descending coronary artery was measured at baseline and at hyperemia during adenosine triphosphate infusion by TTDE to determine CFVR. The CFVR ratio was defined as the ratio of CFVR after beverage consumption to CFVR before beverage consumption. All data were divided into 2 groups according to beverage type: group T (black tea) and group C (caffeine). Two-way analysis of variance showed a significant group effect and interaction in CFVR before and after beverage consumption (p = 0.001). CFVR significantly increased after tea consumption in group T (4.5 +/- 0.9 vs 5.2 +/- 0.9, p <0.0001). The CFVR ratio of group T was larger than that of group C (1.18 +/- 0.07 vs 1.04 +/- 0.08, p = 0.002). Acute black tea consumption improves coronary vessel function, as determined by CFVR.","title":"Black tea increases coronary flow velocity reserve in healthy male subjects."},{"docid":"MED-1707","text":"Sugar-sweetened drinks have been associated with several health problems. In the point narrative as presented below, we provide our opinion and review of the data to date that we need to reconsider consumption of dietary sugar based on the growing concern of obesity and type 2 diabetes. In the counterpoint narrative following our contribution, Drs. Kahn and Sievenpiper provide a defense and suggest that dietary sugar is not the culprit. Data from the National Health and Nutrition Examination Survey and U.S. Department of Agriculture dietary surveys along with commercial Homescan data on household purchases were used to understand changes in sugar and fructose consumption. Meta-analyses and randomized clinical trials were used to evaluate outcomes of beverage and fructose intake. About 75% of all foods and beverages contain added sugar in a large array of forms. Consumption of soft drinks has increased fivefold since 1950. Meta-analyses suggest that consumption of sugar-sweetened beverages (SSBs) is related to the risk of diabetes, the metabolic syndrome, and cardiovascular disease. Drinking two 16-ounce SSBs per day for 6 months induced features of the metabolic syndrome and fatty liver. Randomized controlled trials in children and adults lasting 6 months to 2 years have shown that lowering the intake of soft drinks reduced weight gain. Recent studies suggest a gene-SSB potential relationship. Consumption of calorie-sweetened beverages has continued to increase and plays a role in the epidemic of obesity, the metabolic syndrome, and fatty liver disease. Reducing intake of soft drinks is associated with less weight gain.","title":"Dietary sugar and body weight: have we reached a crisis in the epidemic of obesity and diabetes?: health be damned! Pour on the sugar."},{"docid":"MED-3533","text":"This study ascertained whether a proprietary tart cherry juice blend (CherryPharm, Inc., Geneva, NY, USA) associated with anecdotal reports of sleep enhancement improves subjective reports of insomnia compared to a placebo beverage. The pilot study used a randomized, double-blind, crossover design where each participant received both treatment and placebo for 2 weeks with an intervening 2-week washout period. Sleep continuity (sleep onset, wake after sleep onset, total sleep time, and sleep efficiency) was assessed by 2-week mean values from daily sleep diaries and disease severity by the Insomnia Severity Index in a cohort of 15 older adults with chronic insomnia who were otherwise healthy. The tart cherry juice beverage was associated with statistically significant pre- to post-treatment improvements on all sleep variables. When compared to placebo, the study beverage produced significant reductions in insomnia severity (minutes awake after sleep onset); no such improvements were observed for sleep latency, total sleep time, or sleep efficiency compared to placebo. Effect sizes were moderate and in some cases negligible. The results of this pilot study suggest that CherryPharm, a tart cherry juice blend, has modest beneficial effects on sleep in older adults with insomnia with effect sizes equal to or exceeding those observed in studies of valerian and in some, but not all, studies of melatonin, the two most studied natural products for insomnia. These effects, however, were considerably less than those for evidence-based treatments of insomnia: hypnotic agents and cognitive-behavioral therapies for insomnia.","title":"Effects of a Tart Cherry Juice Beverage on the Sleep of Older Adults with Insomnia: A Pilot Study"},{"docid":"MED-4822","text":"Objective We examined the associations between sweets, sweetened and unsweetened beverages, and sugars and pancreatic cancer risk. Methods We conducted a population-based case–control study (532 cases, 1,701 controls) and used multivariate logistic regression models to calculate odds ratios (OR) and 95% confidence intervals (CI). Because associations were often different by sex, we present results for men and women combined and separately. Results Among men, greater intakes of total and specific sweets were associated with pancreatic cancer risk (total sweets: OR = 1.9, 95% CI: 1.0, 3.6; sweet condiments: OR = 1.9, 95% CI: 1.2, 3.1; chocolate candy: OR = 2.4, 95% CI: 1.1, 5.0; other mixed candy bars: OR = 3.3, 95% CI: 1.5, 7.3 for 1 + servings/day versus none/rarely). Sweets were not consistently associated with risk among women. Sweetened beverages were not associated with increased pancreatic cancer risk. In contrast, low-calorie soft drinks were associated with increased risk among men only; while other low-/non-caloric beverages (e.g., coffee, tea, and water) were unassociated with risk. Of the three sugars assessed (lactose, fructose, and sucrose), only the milk sugar lactose was associated with pancreatic cancer risk (OR = 2.0, 95% CI: 1.5, 2.7 comparing extreme quartiles). Conclusion These results provide limited support for the hypothesis that sweets or sugars increase pancreatic cancer risk.","title":"Sweets, sweetened beverages, and risk of pancreatic cancer in a large population-based case–control study"},{"docid":"MED-5046","text":"Epidemiological evidence suggests a role for tea catechins in reduction of chronic disease risk. However, stability of catechins under digestive conditions is poorly understood. The objective of this study was to characterize the effect of common food additives on digestive recovery of tea catechins. Green tea water extracts were formulated in beverages providing 4.5, 18, 23, and 3.5 mg per 100 mL epicatechin (EC), epigallocatechin (EGC), epigallocatechin-gallate (EGCG), and epicatechin-gallate (ECG), respectively. Common commercial beverage additives; citric acid (CA), BHT, EDTA, ascorbic acid (AA), milk (bovine, soy, and rice), and citrus juice (orange, grapefruit, lemon, and lime) were formulated into finished tea beverages at incremental dosages. Samples were then subjected to in vitro digestion simulating gastric and small intestinal conditions with pre- and post-digestion catechin profiles assessed by HPLC. Catechin stability in green tea was poor with <20% total catechins remaining post-digestion. EGC and EGCG were most sensitive with less, not double equals 10% recovery. Teas formulated with 50% bovine, soy, and rice milk increased total catechin recovery significantly to 52, 55, and 69% respectively. Including 30 mg AA in 250 mL of tea beverage significantly (p<0.05) increased catechin recovery of EGC, EGCG, EC, and ECG to 74, 54, 82, and 45% respectively. Juice preparation resulted in the highest recovery of any formulation for EGC (81-98%), EGCG (56-76%), EC (86-95%), and ECG (30-55%). These data provide evidence that tea consumption practices and formulation factors likely impact catechin digestive recovery and may result in diverse physiological profiles.","title":"Common tea formulations modulate in vitro digestive recovery of green tea catechins."},{"docid":"MED-2219","text":"Our laboratory recently reported that a 3-month exposure of rats to cola-like beverages induced sex hormone changes. The aim of the study was to investigate the effects of various types of Coca-cola intake with different composition for 6 months on oxidative status in testes and testosterone in adult male rats. Fifty adult male Wistar rats were divided into control group drinking water, and groups drinking different Coca-cola beverages (regular Coca-cola, Coca-cola caffeine-free, Coca-cola Light and Coca-cola Zero). Oxidative and carbonyl stress markers were measured in the testicular tissue to assess oxidative status together with testicular and plasma testosterone. StAR expression in testes as a marker of steroidogenesis was quantified. No significant differences were found between the groups in any of the measured parameters. In conclusion, oxidative and carbonyl stress in testicular tissue were not influenced by drinking any type of Coca-cola. Additionally, testosterone in testes and in plasma, as well as testicular StAR expression were comparable among the groups. Copyright © 2013 Elsevier Ltd. All rights reserved.","title":"No harmful effect of different Coca-cola beverages after 6 months of intake on rat testes."},{"docid":"MED-3375","text":"OBJECTIVE: To describe food and beverage types offered and consumed during classroom celebrations at an elementary school in a low-income, urban community. In addition, to report student intake of fresh fruit provided alongside other party foods. METHODS: Observations held during 4 classroom celebrations. Food and beverage items were measured and counted before and after each celebration. Consumption data were recorded in aggregate for the entire classroom and later adjusted to mean intake per student. RESULTS: Majority of items offered were low-nutrient, energy-dense foods. Mean caloric intake during celebrations ranged from 259 to 455 cal. Fruit provided during 2 of the 4 classroom celebrations resulted in a mean intake of 1 full serving per student. CONCLUSIONS AND IMPLICATIONS: Caloric intake from low-nutrient, energy-dense foods and beverages offered during classroom celebrations contributed 20% or more of daily caloric needs. However, fresh fruit may be a reasonable addition to the party food table. Copyright © 2012 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.","title":"Classroom \"cupcake\" celebrations: observations of foods offered and consumed."},{"docid":"MED-2461","text":"This study aimed to evaluate the association of diet with respiratory symptoms and asthma in schoolchildren in Taipei, Taiwan. An in-class interview survey elicited experiences of asthma and respiratory symptoms and consumption frequencies of the major food categories in 2290 fifth graders. Respiratory symptoms surveyed included persistent cough, chest tightness, wheezing with cold, wheezing without cold, dyspnea-associated wheezing, and exercise-induced cough or wheezing. Results showed that the consumption of sweetened beverages had the strongest association with respiratory symptoms and was positively associated with six of the seven respiratory symptoms (all p < 0.05). The adjusted odds ratios (aOR) ranged from 1.05 (95% confidence interval (CI = 1.01-1.09) for exercise-induced cough to 1.09 (95% CI = 1.03-1.16) for wheezing without cold. Egg consumption was associated with 5 of the 7 respiratory symptoms. Consumptions of seafood, soy products, and fruits were each negatively associated with one of the seven respiratory symptoms (all p < 0.05). Consumption of seafood was negatively associated with physician-diagnosed asthma and consumptions of sweetened beverages and eggs were positively associated with suspected asthma (p < 0.05). In conclusion, the study suggests that diet is associated with the respiratory symptoms in schoolchildren in Taipei. Consumptions of sweetened beverages and eggs are associated with increased risk of respiratory symptoms and asthma whereas consumptions of soy products and fruits are associated with reduced risk of respiratory symptoms.","title":"The association of diet with respiratory symptoms and asthma in schoolchildren in Taipei, Taiwan."},{"docid":"MED-4318","text":"Preliminary data in the literature indicate that iron absorption from a meal may be increased when consumed with low-pH beverages such as cola, and it is also possible that sugar iron complexes may alter iron availability. A randomized, crossover trial was conducted to compare the bioavailability of nonheme iron from a vegetarian pizza meal when consumed with 3 different beverages (cola, diet cola, and mineral water). Sixteen women with serum ferritin concentrations of 11-54 µg/L were recruited and completed the study. The pizza meal contained native iron and added ferric chloride solution as a stable isotope extrinsic label; the total iron content of the meal was ~5.3 mg. Incorporation of iron from the meal into RBC was not affected by the type of drink (9.9% with cola, 9.4% with diet cola, and 9.6% with water). Serum ferritin and plasma hepcidin were correlated (r = 0.66; P<0.001) and both were significant predictors of iron bioavailability, but their combined effect explained only 30% of the inter-individual variation (P<0.001) and illustrates the current lack of understanding of mechanisms responsible for the fine-tuning of iron absorption. Although there was no effect of low-pH drinks on iron bioavailability in healthy women, their effect on absorption of fortification iron that requires solubilization in dilute acid, such as reduced iron, and in individuals with low gastric acid production, such as older people and individuals with Helicobacter pylori infection, warrants further investigation.","title":"Low-pH cola beverages do not affect women's iron absorption from a vegetarian meal."},{"docid":"MED-2226","text":"BACKGROUND: Studies of cocoa suggest an array of cardiovascular benefits; however, the effects of daily intake of sugar-free and sugar-sweetened cocoa beverages on endothelial function (EF) have yet to be established. METHODS: 44 adults (BMI 25-35 kg/m2) participated in a randomized, controlled, crossover trial. Participants were randomly assigned to a treatment sequence: sugar-free cocoa beverage, sugar-sweetened cocoa beverage, and sugar-sweetened cocoa-free placebo. Treatments were administered daily for 6 weeks, with a 4-week washout period. RESULTS: Cocoa ingestion improved EF measured as flow-mediated dilation (FMD) compared to placebo (sugar-free cocoa: change, 2.4% [95% CI, 1.5 to 3.2] vs. -0.8% [95% CI, -1.9 to 0.3]; difference, 3.2% [95% CI, 1.8 to 4.6]; p<0.001 and sugar-sweetened cocoa: change, 1.5% [95% CI, 0.6 to 2.4] vs. -0.8% [95% CI, -1.9 to 0.3]; difference, 2.3% [95% CI, 0.9 to 3.7]; p=0.002). The magnitude of improvement in FMD after consumption of sugar-free versus sugar-sweetened cocoa was greater, but not significantly. Other biomarkers of cardiac risk did not change appreciably from baseline. BMI remained stable throughout the study. CONCLUSIONS: Daily cocoa ingestion improves EF independently of other biomarkers of cardiac risk, and does not cause weight gain. Sugar-free preparations may further augment endothelial function. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.","title":"Effects of sugar-sweetened and sugar-free cocoa on endothelial function in overweight adults."},{"docid":"MED-2155","text":"Coffee, after water, is the most widely consumed beverage in the United States, and is the principal source of caffeine intake among adults. The biological effects of coffee may be substantial and are not limited to the actions of caffeine. Coffee is a complex beverage containing hundreds of biologically active compounds, and the health effects of chronic coffee intake are wide ranging. From a cardiovascular (CV) standpoint, coffee consumption may reduce the risk of type 2 diabetes mellitus and hypertension, as well as other conditions associated with CV risk such as obesity and depression; but it may adversely affect lipid profiles depending on how the beverage is prepared. Regardless, a growing body of data suggests that habitual coffee consumption is neutral to beneficial regarding the risks of a variety of adverse CV outcomes including coronary heart disease, congestive heart failure, arrhythmias, and stroke. Moreover, large epidemiological studies suggest that regular coffee drinkers have reduced risks of mortality, both CV and all-cause. The potential benefits also include protection against neurodegenerative diseases, improved asthma control, and lower risk of select gastrointestinal diseases. A daily intake of ∼2 to 3 cups of coffee appears to be safe and is associated with neutral to beneficial effects for most of the studied health outcomes. However, most of the data on coffee's health effects are based on observational data, with very few randomized, controlled studies, and association does not prove causation. Additionally, the possible advantages of regular coffee consumption have to be weighed against potential risks (which are mostly related to its high caffeine content) including anxiety, insomnia, tremulousness, and palpitations, as well as bone loss and possibly increased risk of fractures. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.","title":"Effects of habitual coffee consumption on cardiometabolic disease, cardiovascular health, and all-cause mortality."},{"docid":"MED-4878","text":"Background Telomere length reflects biological aging and may be influenced by environmental factors, including those that affect inflammatory processes. Objective With data from 840 white, black, and Hispanic adults from the Multi-Ethnic Study of Atherosclerosis, we studied cross-sectional associations between telomere length and dietary patterns and foods and beverages that were associated with markers of inflammation. Design Leukocyte telomere length was measured by quantitative polymerase chain reaction. Length was calculated as the amount of telomeric DNA (T) divided by the amount of a single-copy control DNA (S) (T/S ratio). Intake of whole grains, fruit and vegetables, low-fat dairy, nuts or seeds, nonfried fish, coffee, refined grains, fried foods, red meat, processed meat, and sugar-sweetened soda were computed with responses to a 120-item food-frequency questionnaire completed at baseline. Scores on 2 previously defined empirical dietary patterns were also computed for each participant. Results After adjustment for age, other demographics, lifestyle factors, and intakes of other foods or beverages, only processed meat intake was associated with telomere length. For every 1 serving/d greater intake of processed meat, the T/S ratio was 0.07 smaller (β ± SE: −0.07 ± 0.03, P = 0.006). Categorical analysis showed that participants consuming ≥1 serving of processed meat each week had 0.017 smaller T/S ratios than did nonconsumers. Other foods or beverages and the 2 dietary patterns were not associated with telomere length. Conclusions Processed meat intake showed an expected inverse association with telomere length, but other diet features did not show their expected associations.","title":"Dietary patterns, food groups, and telomere length in the Multi-Ethnic Study of Atherosclerosis (MESA)"},{"docid":"MED-5244","text":"Coffee, after water, is the most widely consumed beverage in the United States, and is the principal source of caffeine intake among adults. The biological effects of coffee may be substantial and are not limited to the actions of caffeine. Coffee is a complex beverage containing hundreds of biologically active compounds, and the health effects of chronic coffee intake are wide ranging. From a cardiovascular (CV) standpoint, coffee consumption may reduce the risk of type 2 diabetes mellitus and hypertension, as well as other conditions associated with CV risk such as obesity and depression; but it may adversely affect lipid profiles depending on how the beverage is prepared. Regardless, a growing body of data suggests that habitual coffee consumption is neutral to beneficial regarding the risks of a variety of adverse CV outcomes including coronary heart disease, congestive heart failure, arrhythmias, and stroke. Moreover, large epidemiological studies suggest that regular coffee drinkers have reduced risks of mortality, both CV and all-cause. The potential benefits also include protection against neurodegenerative diseases, improved asthma control, and lower risk of select gastrointestinal diseases. A daily intake of ∼2 to 3 cups of coffee appears to be safe and is associated with neutral to beneficial effects for most of the studied health outcomes. However, most of the data on coffee's health effects are based on observational data, with very few randomized, controlled studies, and association does not prove causation. Additionally, the possible advantages of regular coffee consumption have to be weighed against potential risks (which are mostly related to its high caffeine content) including anxiety, insomnia, tremulousness, and palpitations, as well as bone loss and possibly increased risk of fractures. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.","title":"Effects of habitual coffee consumption on cardiometabolic disease, cardiovascular health, and all-cause mortality."},{"docid":"MED-2491","text":"Exposure limits for arsenic and lead in drinking water have long been established by the U.S. Environmental Protection Agency and new regulations regarding the presence of these contaminants in bottled water went into effect in California in 2009. No comparable exposure limits or regulations are available, however, for juices and other beverages that may contain arsenic and lead. In the study described in this article, 20 apple juices (or ciders), 15 apple-containing juices, one grape, and one citrus juice were analyzed for arsenic and lead. Arsenic was detected in all juices while lead was detected in more than 94% of juices analyzed. Twelve samples (32%) demonstrated arsenic levels nearly at or above the drinking water exposure limit of 10 parts per billion. No juices contained lead above drinking water exposure limits. Expanding drinking water limits to include juices (and other frequently consumed beverages) would better protect consumers while regular testing of these juices would better inform consumers of the risks posed by specific juices and brands.","title":"Arsenic and lead in juice: apple, citrus, and apple-base."},{"docid":"MED-5123","text":"The present paper explores the level of evidence required to justify giving dietary advice to the public. There are important practical differences between the development of public health nutrition guidelines and guidelines for clinical practice. While the gold standard for evidence for clinical practice guidelines is a meta-analysis of a number of randomised controlled trials, this is often unrealistic and sometimes unethical for the evaluation of public health nutrition interventions. Hence, epidemiological studies make up the bulk of evidence for nutrition guidelines. Tea and coffee are an interesting case study in relation to this issue. They are two of the most commonly consumed beverages worldwide, yet there is little dietary advice on their use. The evidence for a relationship between coffee or tea consumption and several diseases is discussed. The available studies, predominantly epidemiological, together with animal and in vitro studies, indicate that coffee and tea are both safe beverages. However, tea is the healthier option because it has a possible role in the prevention of several cancers and CVD. While the evidence for such relationships is not strong, the public will continue to drink both tea and coffee, and will continue to ask nutritionists to make recommendations. It is therefore argued that advice should be given on the best available data, as waiting for complete data to become available could have severe consequences for public health.","title":"Tea or coffee? A case study on evidence for dietary advice."},{"docid":"MED-1621","text":"Except for conflicting evidence about coffee and risk of coronary disease, coffee and tea are not linked to major causes of death. Because of widespread use of both beverages and limitations of prior studies, concern persists. Using Cox models (ten covariates) we studied relations in 128,934 persons to 4501 subsequent deaths. Except for slightly increased risk from acute myocardial infarction among heavier (> or = 4 cups/d) coffee users (relative risk versus nondrinkers = 1.4, 95% confidence interval = 1.0 to 1.9, P = 0.07), there was no increased risk of mortality for all deaths (relative risk per cup of coffee per day = 0.99, 95% confidence interval = 0.97 to 1.01; relative risk per cup of tea per day = 0.98, 95% confidence interval = 0.96 to 1.00) or major causes in adjusted analyses. Coffee was related to lower risk of liver cirrhosis death (relative risk per cup of coffee per day = 0.77, 95% confidence interval = 0.67 to 0.89). Use of both beverages was related to a lower risk of suicide, progressively lower at higher coffee intake (relative risk per cup of coffee per day = 0.87, 95% confidence interval = 0.77 to 0.98). We conclude that coffee and tea have no overall relation to mortality risk. If coffee increases coronary risk, this is balanced by an unexplained lower risk of other conditions, notably cirrhosis and suicide.","title":"Coffee, tea, and mortality."},{"docid":"MED-2677","text":"Population differences in age-related diseases and cancer could stem from differences in diet. To characterize DNA strand-breaking activities in selected foods/beverages, flavorings, and some of their constituent chemicals, we used p53R cells, a cellular assay sensitive to such breaks. Substances testing positive included reference chemicals: quinacrine (peak response, 51X) and etoposide (33X); flavonoids: EGCG (19X), curcumin (12X), apigenin (9X), and quercetin (7X); beverages: chamomile (11X), green (21X), and black tea (26X) and coffee (3 to 29X); and liquid smoke (4 to 28X). Damage occurred at dietary concentrations: etoposide near 5 μg/ml produced responses similar to a 1:1000 dilution of liquid smoke, a 1:20 dilution of coffee, and a 1:5 dilution of tea. Pyrogallol-related chemicals and tannins are present in dietary sources and individually produced strong activity: pyrogallol (30X), 3-methoxycatechol (25X), gallic acid (21X), and 1,2,4-benzenetriol (21X). From structure-activity relationships, high activities depended on specific orientations of hydroxyls on the benzene ring. Responses accompanied cellular signals characteristic of DNA breaks such as H2AX phosphorylation. Breaks were also directly detected by comet assay. Cellular toxicological effects of foods and flavorings could guide epidemiologic and experimental studies of potential disease risks from DNA strand-breaking chemicals in diets.","title":"Biological Clues to Potent DNA-Damaging Activities in Food and Flavoring"},{"docid":"MED-3588","text":"Background Many studies have examined whether caffeine, alcohol, or specific beverages containing these affect fertility in women. However most of these studies have retrospectively collected information on alcohol and caffeine intake, making the results susceptible to biases. Methods We followed 18,555 married women without a history of infertility for 8 years as they attempted to become (or became) pregnant. Diet was measured twice during this period and prospectively related to the incidence of ovulatory disorder infertility. Results There were 438 incident report of ovulatory disorder infertility during follow-up. Intakes of alcohol and caffeine were unrelated to the risk of ovulatory disorder infertility. The multivariate-adjusted relative risk (RR), 95% confidence interval (CI), P for trend comparing the highest to lowest categories of intake were 1.11 (0.76–1.64; 0.78) for alcohol and 0.86 (0.61–1.20; 0.44) for total caffeine. However, intake of caffeinated soft drinks was positively related to ovulatory disorder infertility. The multivariate-adjusted RR 95% CI, and P for trend comparing the highest to lowest categories of caffeinated soft drink consumption were 1.47 (1.09–1.98; 0.01). Similar associations were observed for noncaffeinated, sugared, diet and total soft drinks. Conclusions Our findings do not support the hypothesis that alcohol and caffeine impair ovulation to the point of decreasing fertility. The association between soft drinks and ovulatory disorder infertility appears not to be attributable to their caffeine or sugar content, and deserves further investigation.","title":"Caffeinated and alcoholic beverage intake in relation to ovulatory disorder infertility"},{"docid":"MED-1185","text":"Endogenous sulfite is generated as a consequence of the body's normal processing of sulfur-containing amino acids. Sulfites occur as a consequence of fermentation and also occur naturally in a number of foods and beverages. As food additives, sulfiting agents were first used in 1664 and approved in the United States as long ago as the 1800s. With such long experience with their use, it is easy to understand why these substances have been regarded as safe. They are currently used for a variety of preservative properties, including controlling microbial growth, preventing browning and spoilage, and bleaching some foods. It is estimated that up to 500,000 (< .05% of the population) sulfite-sensitive individuals live in the United States. Sulfite sensitivity occurs most often in asthmatic adults--predominantly women; it is uncommonly reported in preschool children. Adverse reactions to sulfites in nonasthmatics are extremely rare. Asthmatics who are steroid-dependent or who have a higher degree of airway hyperreactivity may be at greater risk of experiencing a reaction to sulfite-containing foods. Even within this limited population, sulfite sensitivity reactions vary widely, ranging from no reaction to severe. The majority of reactions are mild. These manifestations may include dermatologic, respiratory, or gastrointestinal signs and symptoms. Severe nonspecific signs and symptoms occur less commonly. Broncho-constriction is the most common sensitivity response in asthmatics. The precise mechanisms of the sensitivity responses have not been completely elucidated. Inhalation of sulfur dioxide (SO2) generated in the stomach following ingestion of sulfite-containing foods or beverages, a deficiency in a mitochondrial enzyme, and an IgE-mediated immune response have all been implicated.(ABSTRACT TRUNCATED AT 250 WORDS)","title":"Sulfite sensitivity: significance in human health."},{"docid":"MED-1640","text":"Coffee is one of the most widely used pharmacologically active beverages. The present study was designed to evaluate the acute effect of coffee ingestion on endothelial function in healthy individuals, and the potential role of caffeine. We studied 17 healthy young adults (28.9+/-3.0 years old; nine men), who were regular non-heavy coffee drinkers. The endothelial performance was estimated by endothelium-dependent FMD (flow-mediated dilatation) of the brachial artery before and 30, 60, 90 and 120 min after ingestion of a cup of caffeinated coffee (80 mg of caffeine) or the corresponding decaffeinated beverage (< 2 mg of caffeine) in two separate sessions, following a randomized single-blind cross-over design. There was no difference in baseline FMD values between the two sessions [7.78 compared with 7.07% after caffeinated and decaffeinated coffee respectively; P = NS (not significant)]. Caffeinated coffee led to a decline of FMD (7.78, 2.86, 2.12, 4.44 and 4.57% at baseline, 30, 60, 90 and 120 min respectively; P < 0.001). This adverse effect was focused at 30 (P = 0.004) and 60 min (P < 0.001). No significant effect on FMD was found with the decaffeinated coffee session (7.07, 6.24, 5.21, 7.41 and 5.20%; P = NS). The composite effect of the type of coffee consumed over time on FMD was significantly different (P = 0.021). In conclusion, coffee exerts an acute unfavourable effect on the endothelial function in healthy adults, lasting for at least 1 h after intake. This effect might be attributed to caffeine, given that decaffeinated coffee was not associated with any change in the endothelial performance.","title":"Effect of coffee on endothelial function in healthy subjects: the role of caffeine."}],"string":"[\n {\n \"docid\": \"MED-4994\",\n \"text\": \"BACKGROUND: The cardioprotective properties of moderate alcohol consumption, compared with abstinence or heavy drinking, are widely reported, but whether the benefits are experienced equally by all moderate drinkers is less well known. AIMS: To examine the association between average alcohol intake per week and the incidence of fatal and non-fatal myocardial infarction during 17 years of follow-up for 9655 men and women without prevalent disease in the general population; and to test whether the level of cardioprotection differs according to subjects' other health behaviours (healthy, moderately healthy, unhealthy) at entry to the study. METHOD: A longitudinal, British civil service-based cohort study, baseline in 1985-8. RESULTS: A significant benefit of moderate drinking compared with abstinence or heavy drinking was found among those with poor health behaviours (little exercise, poor diet and smokers). No additional benefit from alcohol was found among those with the healthiest behaviour profile (> or =3 hours of vigorous exercise per week, daily fruit or vegetable consumption and non-smokers). CONCLUSION: The cardioprotective benefit from moderate drinking does not apply equally to all drinkers, and this variability should be emphasised in public health messages.\",\n \"title\": \"Who benefits most from the cardioprotective properties of alcohol consumption--health freaks or couch potatoes?\"\n },\n {\n \"docid\": \"MED-1743\",\n \"text\": \"This article describes the nutrient and elemental composition, including residues of herbicides and pesticides, of 31 soybean batches from Iowa, USA. The soy samples were grouped into three different categories: (i) genetically modified, glyphosate-tolerant soy (GM-soy); (ii) unmodified soy cultivated using a conventional \\\"chemical\\\" cultivation regime; and (iii) unmodified soy cultivated using an organic cultivation regime. Organic soybeans showed the healthiest nutritional profile with more sugars, such as glucose, fructose, sucrose and maltose, significantly more total protein, zinc and less fibre than both conventional and GM-soy. Organic soybeans also contained less total saturated fat and total omega-6 fatty acids than both conventional and GM-soy. GM-soy contained high residues of glyphosate and AMPA (mean 3.3 and 5.7 mg/kg, respectively). Conventional and organic soybean batches contained none of these agrochemicals. Using 35 different nutritional and elemental variables to characterise each soy sample, we were able to discriminate GM, conventional and organic soybeans without exception, demonstrating \\\"substantial non-equivalence\\\" in compositional characteristics for 'ready-to-market' soybeans. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.\",\n \"title\": \"Compositional differences in soybeans on the market: glyphosate accumulates in Roundup Ready GM soybeans.\"\n },\n {\n \"docid\": \"MED-1646\",\n \"text\": \"The Beverage Guidance Panel was assembled to provide guidance on the relative health and nutritional benefits and risks of various beverage categories. The beverage panel was initiated by the first author. The Panel's purpose is to attempt to systematically review the literature on beverages and health and provide guidance to the consumer. An additional purpose of the Panel is to develop a deeper dialog among the scientific community on overall beverage consumption patterns in the United States and on the great potential to change this pattern as a way to improve health. Over the past several decades, levels of overweight and obesity have increased across all population groups in the United States. Concurrently, an increased daily intake of 150-300 kcal (for different age-sex groups) has occurred, with approximately 50% of the increased calories coming from the consumption of calorically sweetened beverages. The panel ranked beverages from the lowest to the highest value based on caloric and nutrient contents and related health benefits and risks. Drinking water was ranked as the preferred beverage to fulfill daily water needs and was followed in decreasing value by tea and coffee, low-fat (1.5% or 1%) and skim (nonfat) milk and soy beverages, noncalorically sweetened beverages, beverages with some nutritional benefits (fruit and vegetable juices, whole milk, alcohol, and sports drinks), and calorically sweetened, nutrient-poor beverages. The Panel recommends that the consumption of beverages with no or few calories should take precedence over the consumption of beverages with more calories.\",\n \"title\": \"A new proposed guidance system for beverage consumption in the United States.\"\n },\n {\n \"docid\": \"MED-1710\",\n \"text\": \"Sugar intake in the United States has increased by >40 fold since the American Revolution. The health concerns that have been raised about the amounts of sugar that are in the current diet, primarily as beverages, are the subject of this review. Just less than 50% of the added sugars (sugar and high-fructose corn syrup) are found in soft drinks and fruit drinks. The intake of soft drinks has increased 5-fold between 1950 and 2000. Most meta-analyses have shown that the risk of obesity, diabetes, cardiovascular disease, and metabolic syndrome are related to consumption of beverages sweetened with sugar or high-fructose corn syrup. Calorically sweetened beverage intake has also been related to the risk of nonalcoholic fatty liver disease, and, in men, gout. Calorically sweetened beverages contribute to obesity through their caloric load, and the intake of beverages does not produce a corresponding reduction in the intake of other food, suggesting that beverage calories are “add-on” calories. The increase in plasma triglyceride concentrations by sugar-sweetened beverages can be attributed to fructose rather than glucose in sugar. Several randomized trials of sugar-containing soft drinks versus low-calorie or calorie-free beverages show that either sugar, 50% of which is fructose, or fructose alone increases triglycerides, body weight, visceral adipose tissue, muscle fat, and liver fat. Fructose is metabolized primarily in the liver. When it is taken up by the liver, ATP decreases rapidly as the phosphate is transferred to fructose in a form that makes it easy to convert to lipid precursors. Fructose intake enhances lipogenesis and the production of uric acid. By worsening blood lipids, contributing to obesity, diabetes, fatty liver, and gout, fructose in the amounts currently consumed is hazardous to the health of some people.\",\n \"title\": \"Energy and Fructose From Beverages Sweetened With Sugar or High-Fructose Corn Syrup Pose a Health Risk for Some People\"\n },\n {\n \"docid\": \"MED-1858\",\n \"text\": \"As a hard tissue dental disease, dental erosion has a multifactorial etiology. The majority of dental erosion that originates from extrinsic sources is the result of dietary intake, particularly acidic beverages. Several preventive means have been proposed to minimize the damage to the dentition, including a reduction in the consumption of causative beverages and the adoption of a specific method of drinking, utilizing a straw instead of a cup. This article presents two cases involving the clinical and radiographic features of erosion lesions associated with chronic and excessive intake of acidic carbonated beverages. These examples embody how drinking patterns influence the formation of erosion lesions in various anatomic locations within the dentition. The clinical and radiographic evidence presented in this report cautions against the use of nonspecific terms, such as \\\"cup versus straw,\\\" and instead suggests implementing a more precise description of the suggested method. In view of the extensive damage inflicted by the chronic, excessive intake of carbonated beverages, preventive measures are considered to be the only effective course of management. This article offers illustrative examples of erosion lesions associated with long-term excessive intake of carbonated beverages. The influence of the drinking method--that is, a straw positioned into the labial vestibule versus a cup--on the anatomic location of the erosion lesions will be demonstrated through clinical and radiographic evidence.\",\n \"title\": \"Influence of drinking patterns of carbonated beverages on dental erosion.\"\n },\n {\n \"docid\": \"MED-713\",\n \"text\": \"The effect of beverages prepared from the dried calyx of the flowers of Hibiscus sabdariffa on the excretion of diclofenac was investigated using a controlled study in healthy human volunteers. A high pressure liquid chromatographic method was used to analyse the 8 h urine samples collected after the administration of diclofenac with 300 mL (equivalent to 8.18 mg anthocyanins) of the beverage administered daily for 3 days. An unpaired two-tailed t-test was used to analyse for significant difference observed in the amount of diclofenac excreted before and after administration of the beverage. There was a reduction in the amount of diclofenac excreted and the wide variability observed in the control with the water beverage of Hibiscus sabdariffa (p < 0.05). There is an increasing need to counsel patients against the use of plant beverages with drugs.\",\n \"title\": \"Effects of water extract of Hibiscus sabdariffa, Linn (Malvaceae) 'Roselle' on excretion of a diclofenac formulation.\"\n },\n {\n \"docid\": \"MED-1627\",\n \"text\": \"Sweetened beverages, coffee, and tea are the most consumed non-alcoholic beverages and may have important health consequences. We prospectively evaluated the consumption of various types of beverages assessed in 1995–1996 in relation to self-reported depression diagnosis after 2000 among 263,923 participants of the NIH-AARP Diet and Health Study. Odds ratios (OR) and 95% confidence intervals (CI) were derived from multivariate logistic regressions. The OR (95% CI) comparing ≥4 cans/cups per day with none were 1.30 (95%CI: 1.17–1.44) for soft drinks, 1.38 (1.15–1.65) for fruit drinks, and 0.91 (0.84–0.98) for coffee (all P for trend<0.0001). Null associations were observed for iced-tea and hot tea. In stratified analyses by drinkers of primarily diet versus regular beverages, the ORs were 1.31 (1.16–1.47) for diet versus 1.22 (1.03–1.45) for regular soft drinks, 1.51 (1.18–1.92) for diet versus 1.08 (0.79–1.46) for regular fruit drinks, and 1.25 (1.10–1.41) for diet versus 0.94 (0.83–1.08) for regular sweetened iced-tea. Finally, compared to nondrinkers, drinking coffee or tea without any sweetener was associated with a lower risk for depression, adding artificial sweeteners, but not sugar or honey, was associated with higher risks. Frequent consumption of sweetened beverages, especially diet drinks, may increase depression risk among older adults, whereas coffee consumption may lower the risk.\",\n \"title\": \"Sweetened Beverages, Coffee, and Tea and Depression Risk among Older US Adults\"\n },\n {\n \"docid\": \"MED-897\",\n \"text\": \"The effects of different polyphenol-containing beverages on Fe absorption from a bread meal were estimated in adult human subjects from the erythrocyte incorporation of radio-Fe. The test beverages contained different polyphenol structures and were rich in either phenolic acids (chlorogenic acid in coffee), monomeric flavonoids (herb teas, camomile (Matricaria recutita L.), vervain (Verbena officinalis L.), lime flower (Tilia cordata Mill.), pennyroyal (Mentha pulegium L.) and peppermint (Mentha piperita L.), or complex polyphenol polymerization products (black tea and cocoa). All beverages were potent inhibitors of Fe absorption and reduced absorption in a dose-dependent fashion depending on the content of total polyphenols. Compared with a water control meal, beverages containing 20-50 mg total polyphenols/serving reduced Fe absorption from the bread meal by 50-70%, whereas beverages containing 100-400 mg total polyphenols/serving reduced Fe absorption by 60-90%. Inhibition by black tea was 79-94%, peppermint tea 84%, pennyroyal 73%, cocoa 71%, vervain 59%, lime flower 52% and camomile 47%. At an identical concentration of total polyphenols, black tea was more inhibitory than cocoa, and more inhibitory than herb teas camomile, vervain, lime flower and pennyroyal, but was of equal inhibition to peppermint tea. Adding milk to coffee and tea had little or no influence on their inhibitory nature. Our findings demonstrate that herb teas, as well as black tea, coffee and coca can be potent inhibitors of Fe absorption. This property should be considered when giving dietary advice in relation to Fe nutrition.\",\n \"title\": \"Inhibition of non-haem iron absorption in man by polyphenolic-containing beverages.\"\n },\n {\n \"docid\": \"MED-3763\",\n \"text\": \"The aim of this study was to explore oral exposure to carcinogenic (group 1) acetaldehyde after single sips of strong alcoholic beverages containing no or high concentrations of acetaldehyde. Eight volunteers tasted 5 ml of ethanol diluted to 40 vol.% with no acetaldehyde and 40 vol.% calvados containing 2400 μM acetaldehyde. Salivary acetaldehyde and ethanol concentrations were measured by gas chromatography. The protocol was repeated after ingestion of ethanol (0.5 g/kg body weight). Salivary acetaldehyde concentration was significantly higher after sipping calvados than after sipping ethanol at 30s both with (215 vs. 128 μmol/l, p<0.05) and without (258 vs. 89 μmol/l, p<0.05) alcohol ingestion. From 2 min onwards there were no significant differences in the decreasing salivary acetaldehyde concentration, which remained above the level of carcinogenicity still at 10 min. The systemic alcohol distribution from blood to saliva had no additional effect on salivary acetaldehyde after sipping of the alcoholic beverages. Carcinogenic concentrations of acetaldehyde are produced from ethanol in the oral cavity instantly after a small sip of strong alcoholic beverage, and the exposure continues for at least 10 min. Acetaldehyde present in the beverage has a short-term effect on total acetaldehyde exposure. Copyright © 2011 Elsevier Ltd. All rights reserved.\",\n \"title\": \"A single sip of a strong alcoholic beverage causes exposure to carcinogenic concentrations of acetaldehyde in the oral cavity.\"\n },\n {\n \"docid\": \"MED-918\",\n \"text\": \"Consumption of a large amount of dietary fructose induces gastrointestinal intolerance, and glucose has been known as an enhancer of fructose absorption. Erythritol is a nonglycemic sugar alcohol, and it has been suggested that erythritol is absorbed paracellularly. It was hypothesized that paracellular absorption of erythritol could also enhance paracellular absorption of fructose in healthy adults. This is one of the proposed pathways for how additional glucose enhances the absorption of fructose. Thirty-seven nondiabetic, healthy adults participated in a randomized, double-masked, controlled crossover study. After an overnight fast, participants consumed beverages containing either 50 g fructose and 50 g glucose, 50 g fructose and 33.3 g erythritol (an equimolar concentration of fructose), or 50 g fructose alone. Breath hydrogen response was determined for 8 hours postprandially. Gastrointestinal intolerance symptoms and the number and consistency of bowel movements were recorded for 24 hours postprandially. The breath hydrogen area under the curve (AUC) of the fructose and erythritol beverage was 2 times the AUC of the fructose beverage and 8.75 times the AUC of the fructose and glucose beverage (P < .001, respectively). Compared with fructose and glucose beverage and fructose alone, frequency of watery stools increased (P < .05) and gastrointestinal tolerance worsened (P < .05) when participants consumed fructose and erythritol. These data suggest that coingestion of equimolar concentrations of fructose and erythritol increased carbohydrate malabsorption. Copyright © 2011 Elsevier Inc. All rights reserved.\",\n \"title\": \"Combination of erythritol and fructose increases gastrointestinal symptoms in healthy adults.\"\n },\n {\n \"docid\": \"MED-1637\",\n \"text\": \"Epidemiologic studies suggest that tea consumption decreases the risk for cardiovascular events. However, there has been no clinical report examining the effects of tea consumption on coronary circulation. The purpose of this study was to evaluate the effects of black tea on coronary flow velocity reserve (CFVR) using transthoracic Doppler echocardiography (TTDE). This was a double-blind crossover study of 10 healthy male volunteers conducted to compare the effects of black tea and caffeine on coronary circulation. The coronary flow velocity of the left anterior descending coronary artery was measured at baseline and at hyperemia during adenosine triphosphate infusion by TTDE to determine CFVR. The CFVR ratio was defined as the ratio of CFVR after beverage consumption to CFVR before beverage consumption. All data were divided into 2 groups according to beverage type: group T (black tea) and group C (caffeine). Two-way analysis of variance showed a significant group effect and interaction in CFVR before and after beverage consumption (p = 0.001). CFVR significantly increased after tea consumption in group T (4.5 +/- 0.9 vs 5.2 +/- 0.9, p <0.0001). The CFVR ratio of group T was larger than that of group C (1.18 +/- 0.07 vs 1.04 +/- 0.08, p = 0.002). Acute black tea consumption improves coronary vessel function, as determined by CFVR.\",\n \"title\": \"Black tea increases coronary flow velocity reserve in healthy male subjects.\"\n },\n {\n \"docid\": \"MED-1707\",\n \"text\": \"Sugar-sweetened drinks have been associated with several health problems. In the point narrative as presented below, we provide our opinion and review of the data to date that we need to reconsider consumption of dietary sugar based on the growing concern of obesity and type 2 diabetes. In the counterpoint narrative following our contribution, Drs. Kahn and Sievenpiper provide a defense and suggest that dietary sugar is not the culprit. Data from the National Health and Nutrition Examination Survey and U.S. Department of Agriculture dietary surveys along with commercial Homescan data on household purchases were used to understand changes in sugar and fructose consumption. Meta-analyses and randomized clinical trials were used to evaluate outcomes of beverage and fructose intake. About 75% of all foods and beverages contain added sugar in a large array of forms. Consumption of soft drinks has increased fivefold since 1950. Meta-analyses suggest that consumption of sugar-sweetened beverages (SSBs) is related to the risk of diabetes, the metabolic syndrome, and cardiovascular disease. Drinking two 16-ounce SSBs per day for 6 months induced features of the metabolic syndrome and fatty liver. Randomized controlled trials in children and adults lasting 6 months to 2 years have shown that lowering the intake of soft drinks reduced weight gain. Recent studies suggest a gene-SSB potential relationship. Consumption of calorie-sweetened beverages has continued to increase and plays a role in the epidemic of obesity, the metabolic syndrome, and fatty liver disease. Reducing intake of soft drinks is associated with less weight gain.\",\n \"title\": \"Dietary sugar and body weight: have we reached a crisis in the epidemic of obesity and diabetes?: health be damned! Pour on the sugar.\"\n },\n {\n \"docid\": \"MED-3533\",\n \"text\": \"This study ascertained whether a proprietary tart cherry juice blend (CherryPharm, Inc., Geneva, NY, USA) associated with anecdotal reports of sleep enhancement improves subjective reports of insomnia compared to a placebo beverage. The pilot study used a randomized, double-blind, crossover design where each participant received both treatment and placebo for 2 weeks with an intervening 2-week washout period. Sleep continuity (sleep onset, wake after sleep onset, total sleep time, and sleep efficiency) was assessed by 2-week mean values from daily sleep diaries and disease severity by the Insomnia Severity Index in a cohort of 15 older adults with chronic insomnia who were otherwise healthy. The tart cherry juice beverage was associated with statistically significant pre- to post-treatment improvements on all sleep variables. When compared to placebo, the study beverage produced significant reductions in insomnia severity (minutes awake after sleep onset); no such improvements were observed for sleep latency, total sleep time, or sleep efficiency compared to placebo. Effect sizes were moderate and in some cases negligible. The results of this pilot study suggest that CherryPharm, a tart cherry juice blend, has modest beneficial effects on sleep in older adults with insomnia with effect sizes equal to or exceeding those observed in studies of valerian and in some, but not all, studies of melatonin, the two most studied natural products for insomnia. These effects, however, were considerably less than those for evidence-based treatments of insomnia: hypnotic agents and cognitive-behavioral therapies for insomnia.\",\n \"title\": \"Effects of a Tart Cherry Juice Beverage on the Sleep of Older Adults with Insomnia: A Pilot Study\"\n },\n {\n \"docid\": \"MED-4822\",\n \"text\": \"Objective We examined the associations between sweets, sweetened and unsweetened beverages, and sugars and pancreatic cancer risk. Methods We conducted a population-based case–control study (532 cases, 1,701 controls) and used multivariate logistic regression models to calculate odds ratios (OR) and 95% confidence intervals (CI). Because associations were often different by sex, we present results for men and women combined and separately. Results Among men, greater intakes of total and specific sweets were associated with pancreatic cancer risk (total sweets: OR = 1.9, 95% CI: 1.0, 3.6; sweet condiments: OR = 1.9, 95% CI: 1.2, 3.1; chocolate candy: OR = 2.4, 95% CI: 1.1, 5.0; other mixed candy bars: OR = 3.3, 95% CI: 1.5, 7.3 for 1 + servings/day versus none/rarely). Sweets were not consistently associated with risk among women. Sweetened beverages were not associated with increased pancreatic cancer risk. In contrast, low-calorie soft drinks were associated with increased risk among men only; while other low-/non-caloric beverages (e.g., coffee, tea, and water) were unassociated with risk. Of the three sugars assessed (lactose, fructose, and sucrose), only the milk sugar lactose was associated with pancreatic cancer risk (OR = 2.0, 95% CI: 1.5, 2.7 comparing extreme quartiles). Conclusion These results provide limited support for the hypothesis that sweets or sugars increase pancreatic cancer risk.\",\n \"title\": \"Sweets, sweetened beverages, and risk of pancreatic cancer in a large population-based case–control study\"\n },\n {\n \"docid\": \"MED-5046\",\n \"text\": \"Epidemiological evidence suggests a role for tea catechins in reduction of chronic disease risk. However, stability of catechins under digestive conditions is poorly understood. The objective of this study was to characterize the effect of common food additives on digestive recovery of tea catechins. Green tea water extracts were formulated in beverages providing 4.5, 18, 23, and 3.5 mg per 100 mL epicatechin (EC), epigallocatechin (EGC), epigallocatechin-gallate (EGCG), and epicatechin-gallate (ECG), respectively. Common commercial beverage additives; citric acid (CA), BHT, EDTA, ascorbic acid (AA), milk (bovine, soy, and rice), and citrus juice (orange, grapefruit, lemon, and lime) were formulated into finished tea beverages at incremental dosages. Samples were then subjected to in vitro digestion simulating gastric and small intestinal conditions with pre- and post-digestion catechin profiles assessed by HPLC. Catechin stability in green tea was poor with <20% total catechins remaining post-digestion. EGC and EGCG were most sensitive with less, not double equals 10% recovery. Teas formulated with 50% bovine, soy, and rice milk increased total catechin recovery significantly to 52, 55, and 69% respectively. Including 30 mg AA in 250 mL of tea beverage significantly (p<0.05) increased catechin recovery of EGC, EGCG, EC, and ECG to 74, 54, 82, and 45% respectively. Juice preparation resulted in the highest recovery of any formulation for EGC (81-98%), EGCG (56-76%), EC (86-95%), and ECG (30-55%). These data provide evidence that tea consumption practices and formulation factors likely impact catechin digestive recovery and may result in diverse physiological profiles.\",\n \"title\": \"Common tea formulations modulate in vitro digestive recovery of green tea catechins.\"\n },\n {\n \"docid\": \"MED-2219\",\n \"text\": \"Our laboratory recently reported that a 3-month exposure of rats to cola-like beverages induced sex hormone changes. The aim of the study was to investigate the effects of various types of Coca-cola intake with different composition for 6 months on oxidative status in testes and testosterone in adult male rats. Fifty adult male Wistar rats were divided into control group drinking water, and groups drinking different Coca-cola beverages (regular Coca-cola, Coca-cola caffeine-free, Coca-cola Light and Coca-cola Zero). Oxidative and carbonyl stress markers were measured in the testicular tissue to assess oxidative status together with testicular and plasma testosterone. StAR expression in testes as a marker of steroidogenesis was quantified. No significant differences were found between the groups in any of the measured parameters. In conclusion, oxidative and carbonyl stress in testicular tissue were not influenced by drinking any type of Coca-cola. Additionally, testosterone in testes and in plasma, as well as testicular StAR expression were comparable among the groups. Copyright © 2013 Elsevier Ltd. All rights reserved.\",\n \"title\": \"No harmful effect of different Coca-cola beverages after 6 months of intake on rat testes.\"\n },\n {\n \"docid\": \"MED-3375\",\n \"text\": \"OBJECTIVE: To describe food and beverage types offered and consumed during classroom celebrations at an elementary school in a low-income, urban community. In addition, to report student intake of fresh fruit provided alongside other party foods. METHODS: Observations held during 4 classroom celebrations. Food and beverage items were measured and counted before and after each celebration. Consumption data were recorded in aggregate for the entire classroom and later adjusted to mean intake per student. RESULTS: Majority of items offered were low-nutrient, energy-dense foods. Mean caloric intake during celebrations ranged from 259 to 455 cal. Fruit provided during 2 of the 4 classroom celebrations resulted in a mean intake of 1 full serving per student. CONCLUSIONS AND IMPLICATIONS: Caloric intake from low-nutrient, energy-dense foods and beverages offered during classroom celebrations contributed 20% or more of daily caloric needs. However, fresh fruit may be a reasonable addition to the party food table. Copyright © 2012 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.\",\n \"title\": \"Classroom \\\"cupcake\\\" celebrations: observations of foods offered and consumed.\"\n },\n {\n \"docid\": \"MED-2461\",\n \"text\": \"This study aimed to evaluate the association of diet with respiratory symptoms and asthma in schoolchildren in Taipei, Taiwan. An in-class interview survey elicited experiences of asthma and respiratory symptoms and consumption frequencies of the major food categories in 2290 fifth graders. Respiratory symptoms surveyed included persistent cough, chest tightness, wheezing with cold, wheezing without cold, dyspnea-associated wheezing, and exercise-induced cough or wheezing. Results showed that the consumption of sweetened beverages had the strongest association with respiratory symptoms and was positively associated with six of the seven respiratory symptoms (all p < 0.05). The adjusted odds ratios (aOR) ranged from 1.05 (95% confidence interval (CI = 1.01-1.09) for exercise-induced cough to 1.09 (95% CI = 1.03-1.16) for wheezing without cold. Egg consumption was associated with 5 of the 7 respiratory symptoms. Consumptions of seafood, soy products, and fruits were each negatively associated with one of the seven respiratory symptoms (all p < 0.05). Consumption of seafood was negatively associated with physician-diagnosed asthma and consumptions of sweetened beverages and eggs were positively associated with suspected asthma (p < 0.05). In conclusion, the study suggests that diet is associated with the respiratory symptoms in schoolchildren in Taipei. Consumptions of sweetened beverages and eggs are associated with increased risk of respiratory symptoms and asthma whereas consumptions of soy products and fruits are associated with reduced risk of respiratory symptoms.\",\n \"title\": \"The association of diet with respiratory symptoms and asthma in schoolchildren in Taipei, Taiwan.\"\n },\n {\n \"docid\": \"MED-4318\",\n \"text\": \"Preliminary data in the literature indicate that iron absorption from a meal may be increased when consumed with low-pH beverages such as cola, and it is also possible that sugar iron complexes may alter iron availability. A randomized, crossover trial was conducted to compare the bioavailability of nonheme iron from a vegetarian pizza meal when consumed with 3 different beverages (cola, diet cola, and mineral water). Sixteen women with serum ferritin concentrations of 11-54 µg/L were recruited and completed the study. The pizza meal contained native iron and added ferric chloride solution as a stable isotope extrinsic label; the total iron content of the meal was ~5.3 mg. Incorporation of iron from the meal into RBC was not affected by the type of drink (9.9% with cola, 9.4% with diet cola, and 9.6% with water). Serum ferritin and plasma hepcidin were correlated (r = 0.66; P<0.001) and both were significant predictors of iron bioavailability, but their combined effect explained only 30% of the inter-individual variation (P<0.001) and illustrates the current lack of understanding of mechanisms responsible for the fine-tuning of iron absorption. Although there was no effect of low-pH drinks on iron bioavailability in healthy women, their effect on absorption of fortification iron that requires solubilization in dilute acid, such as reduced iron, and in individuals with low gastric acid production, such as older people and individuals with Helicobacter pylori infection, warrants further investigation.\",\n \"title\": \"Low-pH cola beverages do not affect women's iron absorption from a vegetarian meal.\"\n },\n {\n \"docid\": \"MED-2226\",\n \"text\": \"BACKGROUND: Studies of cocoa suggest an array of cardiovascular benefits; however, the effects of daily intake of sugar-free and sugar-sweetened cocoa beverages on endothelial function (EF) have yet to be established. METHODS: 44 adults (BMI 25-35 kg/m2) participated in a randomized, controlled, crossover trial. Participants were randomly assigned to a treatment sequence: sugar-free cocoa beverage, sugar-sweetened cocoa beverage, and sugar-sweetened cocoa-free placebo. Treatments were administered daily for 6 weeks, with a 4-week washout period. RESULTS: Cocoa ingestion improved EF measured as flow-mediated dilation (FMD) compared to placebo (sugar-free cocoa: change, 2.4% [95% CI, 1.5 to 3.2] vs. -0.8% [95% CI, -1.9 to 0.3]; difference, 3.2% [95% CI, 1.8 to 4.6]; p<0.001 and sugar-sweetened cocoa: change, 1.5% [95% CI, 0.6 to 2.4] vs. -0.8% [95% CI, -1.9 to 0.3]; difference, 2.3% [95% CI, 0.9 to 3.7]; p=0.002). The magnitude of improvement in FMD after consumption of sugar-free versus sugar-sweetened cocoa was greater, but not significantly. Other biomarkers of cardiac risk did not change appreciably from baseline. BMI remained stable throughout the study. CONCLUSIONS: Daily cocoa ingestion improves EF independently of other biomarkers of cardiac risk, and does not cause weight gain. Sugar-free preparations may further augment endothelial function. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.\",\n \"title\": \"Effects of sugar-sweetened and sugar-free cocoa on endothelial function in overweight adults.\"\n },\n {\n \"docid\": \"MED-2155\",\n \"text\": \"Coffee, after water, is the most widely consumed beverage in the United States, and is the principal source of caffeine intake among adults. The biological effects of coffee may be substantial and are not limited to the actions of caffeine. Coffee is a complex beverage containing hundreds of biologically active compounds, and the health effects of chronic coffee intake are wide ranging. From a cardiovascular (CV) standpoint, coffee consumption may reduce the risk of type 2 diabetes mellitus and hypertension, as well as other conditions associated with CV risk such as obesity and depression; but it may adversely affect lipid profiles depending on how the beverage is prepared. Regardless, a growing body of data suggests that habitual coffee consumption is neutral to beneficial regarding the risks of a variety of adverse CV outcomes including coronary heart disease, congestive heart failure, arrhythmias, and stroke. Moreover, large epidemiological studies suggest that regular coffee drinkers have reduced risks of mortality, both CV and all-cause. The potential benefits also include protection against neurodegenerative diseases, improved asthma control, and lower risk of select gastrointestinal diseases. A daily intake of ∼2 to 3 cups of coffee appears to be safe and is associated with neutral to beneficial effects for most of the studied health outcomes. However, most of the data on coffee's health effects are based on observational data, with very few randomized, controlled studies, and association does not prove causation. Additionally, the possible advantages of regular coffee consumption have to be weighed against potential risks (which are mostly related to its high caffeine content) including anxiety, insomnia, tremulousness, and palpitations, as well as bone loss and possibly increased risk of fractures. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.\",\n \"title\": \"Effects of habitual coffee consumption on cardiometabolic disease, cardiovascular health, and all-cause mortality.\"\n },\n {\n \"docid\": \"MED-4878\",\n \"text\": \"Background Telomere length reflects biological aging and may be influenced by environmental factors, including those that affect inflammatory processes. Objective With data from 840 white, black, and Hispanic adults from the Multi-Ethnic Study of Atherosclerosis, we studied cross-sectional associations between telomere length and dietary patterns and foods and beverages that were associated with markers of inflammation. Design Leukocyte telomere length was measured by quantitative polymerase chain reaction. Length was calculated as the amount of telomeric DNA (T) divided by the amount of a single-copy control DNA (S) (T/S ratio). Intake of whole grains, fruit and vegetables, low-fat dairy, nuts or seeds, nonfried fish, coffee, refined grains, fried foods, red meat, processed meat, and sugar-sweetened soda were computed with responses to a 120-item food-frequency questionnaire completed at baseline. Scores on 2 previously defined empirical dietary patterns were also computed for each participant. Results After adjustment for age, other demographics, lifestyle factors, and intakes of other foods or beverages, only processed meat intake was associated with telomere length. For every 1 serving/d greater intake of processed meat, the T/S ratio was 0.07 smaller (β ± SE: −0.07 ± 0.03, P = 0.006). Categorical analysis showed that participants consuming ≥1 serving of processed meat each week had 0.017 smaller T/S ratios than did nonconsumers. Other foods or beverages and the 2 dietary patterns were not associated with telomere length. Conclusions Processed meat intake showed an expected inverse association with telomere length, but other diet features did not show their expected associations.\",\n \"title\": \"Dietary patterns, food groups, and telomere length in the Multi-Ethnic Study of Atherosclerosis (MESA)\"\n },\n {\n \"docid\": \"MED-5244\",\n \"text\": \"Coffee, after water, is the most widely consumed beverage in the United States, and is the principal source of caffeine intake among adults. The biological effects of coffee may be substantial and are not limited to the actions of caffeine. Coffee is a complex beverage containing hundreds of biologically active compounds, and the health effects of chronic coffee intake are wide ranging. From a cardiovascular (CV) standpoint, coffee consumption may reduce the risk of type 2 diabetes mellitus and hypertension, as well as other conditions associated with CV risk such as obesity and depression; but it may adversely affect lipid profiles depending on how the beverage is prepared. Regardless, a growing body of data suggests that habitual coffee consumption is neutral to beneficial regarding the risks of a variety of adverse CV outcomes including coronary heart disease, congestive heart failure, arrhythmias, and stroke. Moreover, large epidemiological studies suggest that regular coffee drinkers have reduced risks of mortality, both CV and all-cause. The potential benefits also include protection against neurodegenerative diseases, improved asthma control, and lower risk of select gastrointestinal diseases. A daily intake of ∼2 to 3 cups of coffee appears to be safe and is associated with neutral to beneficial effects for most of the studied health outcomes. However, most of the data on coffee's health effects are based on observational data, with very few randomized, controlled studies, and association does not prove causation. Additionally, the possible advantages of regular coffee consumption have to be weighed against potential risks (which are mostly related to its high caffeine content) including anxiety, insomnia, tremulousness, and palpitations, as well as bone loss and possibly increased risk of fractures. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.\",\n \"title\": \"Effects of habitual coffee consumption on cardiometabolic disease, cardiovascular health, and all-cause mortality.\"\n },\n {\n \"docid\": \"MED-2491\",\n \"text\": \"Exposure limits for arsenic and lead in drinking water have long been established by the U.S. Environmental Protection Agency and new regulations regarding the presence of these contaminants in bottled water went into effect in California in 2009. No comparable exposure limits or regulations are available, however, for juices and other beverages that may contain arsenic and lead. In the study described in this article, 20 apple juices (or ciders), 15 apple-containing juices, one grape, and one citrus juice were analyzed for arsenic and lead. Arsenic was detected in all juices while lead was detected in more than 94% of juices analyzed. Twelve samples (32%) demonstrated arsenic levels nearly at or above the drinking water exposure limit of 10 parts per billion. No juices contained lead above drinking water exposure limits. Expanding drinking water limits to include juices (and other frequently consumed beverages) would better protect consumers while regular testing of these juices would better inform consumers of the risks posed by specific juices and brands.\",\n \"title\": \"Arsenic and lead in juice: apple, citrus, and apple-base.\"\n },\n {\n \"docid\": \"MED-5123\",\n \"text\": \"The present paper explores the level of evidence required to justify giving dietary advice to the public. There are important practical differences between the development of public health nutrition guidelines and guidelines for clinical practice. While the gold standard for evidence for clinical practice guidelines is a meta-analysis of a number of randomised controlled trials, this is often unrealistic and sometimes unethical for the evaluation of public health nutrition interventions. Hence, epidemiological studies make up the bulk of evidence for nutrition guidelines. Tea and coffee are an interesting case study in relation to this issue. They are two of the most commonly consumed beverages worldwide, yet there is little dietary advice on their use. The evidence for a relationship between coffee or tea consumption and several diseases is discussed. The available studies, predominantly epidemiological, together with animal and in vitro studies, indicate that coffee and tea are both safe beverages. However, tea is the healthier option because it has a possible role in the prevention of several cancers and CVD. While the evidence for such relationships is not strong, the public will continue to drink both tea and coffee, and will continue to ask nutritionists to make recommendations. It is therefore argued that advice should be given on the best available data, as waiting for complete data to become available could have severe consequences for public health.\",\n \"title\": \"Tea or coffee? A case study on evidence for dietary advice.\"\n },\n {\n \"docid\": \"MED-1621\",\n \"text\": \"Except for conflicting evidence about coffee and risk of coronary disease, coffee and tea are not linked to major causes of death. Because of widespread use of both beverages and limitations of prior studies, concern persists. Using Cox models (ten covariates) we studied relations in 128,934 persons to 4501 subsequent deaths. Except for slightly increased risk from acute myocardial infarction among heavier (> or = 4 cups/d) coffee users (relative risk versus nondrinkers = 1.4, 95% confidence interval = 1.0 to 1.9, P = 0.07), there was no increased risk of mortality for all deaths (relative risk per cup of coffee per day = 0.99, 95% confidence interval = 0.97 to 1.01; relative risk per cup of tea per day = 0.98, 95% confidence interval = 0.96 to 1.00) or major causes in adjusted analyses. Coffee was related to lower risk of liver cirrhosis death (relative risk per cup of coffee per day = 0.77, 95% confidence interval = 0.67 to 0.89). Use of both beverages was related to a lower risk of suicide, progressively lower at higher coffee intake (relative risk per cup of coffee per day = 0.87, 95% confidence interval = 0.77 to 0.98). We conclude that coffee and tea have no overall relation to mortality risk. If coffee increases coronary risk, this is balanced by an unexplained lower risk of other conditions, notably cirrhosis and suicide.\",\n \"title\": \"Coffee, tea, and mortality.\"\n },\n {\n \"docid\": \"MED-2677\",\n \"text\": \"Population differences in age-related diseases and cancer could stem from differences in diet. To characterize DNA strand-breaking activities in selected foods/beverages, flavorings, and some of their constituent chemicals, we used p53R cells, a cellular assay sensitive to such breaks. Substances testing positive included reference chemicals: quinacrine (peak response, 51X) and etoposide (33X); flavonoids: EGCG (19X), curcumin (12X), apigenin (9X), and quercetin (7X); beverages: chamomile (11X), green (21X), and black tea (26X) and coffee (3 to 29X); and liquid smoke (4 to 28X). Damage occurred at dietary concentrations: etoposide near 5 μg/ml produced responses similar to a 1:1000 dilution of liquid smoke, a 1:20 dilution of coffee, and a 1:5 dilution of tea. Pyrogallol-related chemicals and tannins are present in dietary sources and individually produced strong activity: pyrogallol (30X), 3-methoxycatechol (25X), gallic acid (21X), and 1,2,4-benzenetriol (21X). From structure-activity relationships, high activities depended on specific orientations of hydroxyls on the benzene ring. Responses accompanied cellular signals characteristic of DNA breaks such as H2AX phosphorylation. Breaks were also directly detected by comet assay. Cellular toxicological effects of foods and flavorings could guide epidemiologic and experimental studies of potential disease risks from DNA strand-breaking chemicals in diets.\",\n \"title\": \"Biological Clues to Potent DNA-Damaging Activities in Food and Flavoring\"\n },\n {\n \"docid\": \"MED-3588\",\n \"text\": \"Background Many studies have examined whether caffeine, alcohol, or specific beverages containing these affect fertility in women. However most of these studies have retrospectively collected information on alcohol and caffeine intake, making the results susceptible to biases. Methods We followed 18,555 married women without a history of infertility for 8 years as they attempted to become (or became) pregnant. Diet was measured twice during this period and prospectively related to the incidence of ovulatory disorder infertility. Results There were 438 incident report of ovulatory disorder infertility during follow-up. Intakes of alcohol and caffeine were unrelated to the risk of ovulatory disorder infertility. The multivariate-adjusted relative risk (RR), 95% confidence interval (CI), P for trend comparing the highest to lowest categories of intake were 1.11 (0.76–1.64; 0.78) for alcohol and 0.86 (0.61–1.20; 0.44) for total caffeine. However, intake of caffeinated soft drinks was positively related to ovulatory disorder infertility. The multivariate-adjusted RR 95% CI, and P for trend comparing the highest to lowest categories of caffeinated soft drink consumption were 1.47 (1.09–1.98; 0.01). Similar associations were observed for noncaffeinated, sugared, diet and total soft drinks. Conclusions Our findings do not support the hypothesis that alcohol and caffeine impair ovulation to the point of decreasing fertility. The association between soft drinks and ovulatory disorder infertility appears not to be attributable to their caffeine or sugar content, and deserves further investigation.\",\n \"title\": \"Caffeinated and alcoholic beverage intake in relation to ovulatory disorder infertility\"\n },\n {\n \"docid\": \"MED-1185\",\n \"text\": \"Endogenous sulfite is generated as a consequence of the body's normal processing of sulfur-containing amino acids. Sulfites occur as a consequence of fermentation and also occur naturally in a number of foods and beverages. As food additives, sulfiting agents were first used in 1664 and approved in the United States as long ago as the 1800s. With such long experience with their use, it is easy to understand why these substances have been regarded as safe. They are currently used for a variety of preservative properties, including controlling microbial growth, preventing browning and spoilage, and bleaching some foods. It is estimated that up to 500,000 (< .05% of the population) sulfite-sensitive individuals live in the United States. Sulfite sensitivity occurs most often in asthmatic adults--predominantly women; it is uncommonly reported in preschool children. Adverse reactions to sulfites in nonasthmatics are extremely rare. Asthmatics who are steroid-dependent or who have a higher degree of airway hyperreactivity may be at greater risk of experiencing a reaction to sulfite-containing foods. Even within this limited population, sulfite sensitivity reactions vary widely, ranging from no reaction to severe. The majority of reactions are mild. These manifestations may include dermatologic, respiratory, or gastrointestinal signs and symptoms. Severe nonspecific signs and symptoms occur less commonly. Broncho-constriction is the most common sensitivity response in asthmatics. The precise mechanisms of the sensitivity responses have not been completely elucidated. Inhalation of sulfur dioxide (SO2) generated in the stomach following ingestion of sulfite-containing foods or beverages, a deficiency in a mitochondrial enzyme, and an IgE-mediated immune response have all been implicated.(ABSTRACT TRUNCATED AT 250 WORDS)\",\n \"title\": \"Sulfite sensitivity: significance in human health.\"\n },\n {\n \"docid\": \"MED-1640\",\n \"text\": \"Coffee is one of the most widely used pharmacologically active beverages. The present study was designed to evaluate the acute effect of coffee ingestion on endothelial function in healthy individuals, and the potential role of caffeine. We studied 17 healthy young adults (28.9+/-3.0 years old; nine men), who were regular non-heavy coffee drinkers. The endothelial performance was estimated by endothelium-dependent FMD (flow-mediated dilatation) of the brachial artery before and 30, 60, 90 and 120 min after ingestion of a cup of caffeinated coffee (80 mg of caffeine) or the corresponding decaffeinated beverage (< 2 mg of caffeine) in two separate sessions, following a randomized single-blind cross-over design. There was no difference in baseline FMD values between the two sessions [7.78 compared with 7.07% after caffeinated and decaffeinated coffee respectively; P = NS (not significant)]. Caffeinated coffee led to a decline of FMD (7.78, 2.86, 2.12, 4.44 and 4.57% at baseline, 30, 60, 90 and 120 min respectively; P < 0.001). This adverse effect was focused at 30 (P = 0.004) and 60 min (P < 0.001). No significant effect on FMD was found with the decaffeinated coffee session (7.07, 6.24, 5.21, 7.41 and 5.20%; P = NS). The composite effect of the type of coffee consumed over time on FMD was significantly different (P = 0.021). In conclusion, coffee exerts an acute unfavourable effect on the endothelial function in healthy adults, lasting for at least 1 h after intake. This effect might be attributed to caffeine, given that decaffeinated coffee was not associated with any change in the endothelial performance.\",\n \"title\": \"Effect of coffee on endothelial function in healthy subjects: the role of caffeine.\"\n }\n]"}}},{"rowIdx":187,"cells":{"query_id":{"kind":"string","value":"5a88b2a55542994846c1cebe"},"query":{"kind":"string","value":"Carol Thurston starred in eight episodes of \"The Life and Legend of Wyatt Earp\" and also in which 1953 film directed by Spencer G. Bennet?"},"positive_passages":{"kind":"list like","value":[{"docid":"40512719","text":"Killer Ape (1953) is the twelfth Jungle Jim film produced by Columbia Pictures. It features Johnny Weissmuller in his twelfth performance as the protagonist adventurer Jungle Jim. Carol Thurston also stars. The film was directed by Spencer G. Bennet and written by Arthur Hoerl and Carroll Young.","title":""},{"docid":"30110136","text":"Carol Thurston (September 27, 1920 – December 31, 1969) was an American film and television actress who played the fictitious Emma Clanton in eight episodes (1959-1961) of the ABC/Desilu western television series, \"The Life and Legend of Wyatt Earp\", starring Hugh O'Brian as frontier peace officer Wyatt Earp.","title":""}],"string":"[\n {\n \"docid\": \"40512719\",\n \"text\": \"Killer Ape (1953) is the twelfth Jungle Jim film produced by Columbia Pictures. It features Johnny Weissmuller in his twelfth performance as the protagonist adventurer Jungle Jim. Carol Thurston also stars. The film was directed by Spencer G. Bennet and written by Arthur Hoerl and Carroll Young.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"30110136\",\n \"text\": \"Carol Thurston (September 27, 1920 – December 31, 1969) was an American film and television actress who played the fictitious Emma Clanton in eight episodes (1959-1961) of the ABC/Desilu western television series, \\\"The Life and Legend of Wyatt Earp\\\", starring Hugh O'Brian as frontier peace officer Wyatt Earp.\",\n \"title\": \"\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"42773781","text":"Jimmy Noel (May 15, 1903–January 31, 1985) was a Massachusetts-born actor and stuntman who appeared in hundreds of largely uncredited roles in film and television between 1949 and 1975. He appeared 202 times on CBS's western series, \"Gunsmoke\", starring James Arness, and in 144 episodes of the ABC/Desilu production, \"The Life and Legend of Wyatt Earp\", with Hugh O'Brian in the title role of deputy Marshal Wyatt Earp. Buddy Roosevelt made similar appearances in sixty-five \"Wyatt Earp\" episodes.","title":""},{"docid":"16537645","text":"Frederick Hazlitt Brennan (September 23, 1901 – June 30, 1962) was an American screenwriter of more than thirty films between 1929 and 1953 and the director of the ABC/Desilu western television series, \"The Life and Legend of Wyatt Earp\" (1955-1961), starring Hugh O'Brian as deputy Marshal Wyatt Earp.","title":""},{"docid":"1998796","text":"The Life and Legend of Wyatt Earp is the first western television series written for adults, premiering four days before \"Gunsmoke\" on September 6, 1955. It is loosely based on the life of frontier marshal Wyatt Earp. The half-hour black-and-white program aired for 6 seasons (229 episodes) on ABC from 1955 to 1961 and featured Hugh O'Brian in the title role.","title":""},{"docid":"36406131","text":"Wyatt Earp: Return to Tombstone is a 1994 independent film starring Hugh O'Brian as Wyatt Earp, featuring new footage mixed with colorized sequences from O'Brian's 1955-1961 television series \"The Life and Legend of Wyatt Earp\". The supporting cast for the new footage includes Bruce Boxleitner, Paul Brinegar, Harry Carey, Jr., Bo Hopkins, and Don Meredith. The colorized flashback archival footage from the original television series features Douglas Fowley as Doc Holliday and Lloyd Corrigan as Ned Buntline. The movie was directed by Paul Landres and Frank McDonald.","title":""},{"docid":"42543113","text":"Raymond C. Boyle, known as Ray Boyle or as the screen name Dirk London (born June 28, 1925), is an American actor known principally for his sporadic role as Morgan Earp, the brother of Wyatt Earp in fifteen episodes of the ABC/Desilu Productions western television series, \"The Life and Legend of Wyatt Earp,\" starring Hugh O'Brian in the title role. Boyle's episodes began with \"The Assassins\" in 1956 and ended with \"The Outlaws Cry Murder\" in 1961.","title":""},{"docid":"23440679","text":"Carol Montgomery Stone (February 1, 1915 – June 10, 2011) was an actress who played \"Big Nose Kate\", or Kate Holliday, the common law wife of Doc Holliday, in ten episodes in the 1957-1958 season of the ABC/Desilu western television series, \"The Life and Legend of Wyatt Earp\".","title":""},{"docid":"39941754","text":"Mason Alan Dinehart (born April 30, 1936), also known as Mason Alan Dinehart III, Alan Dinehart III, or Mase Dinehart, is an American businessman and former actor best known for his role as a youthful Bat Masterson in thirty-four episodes between 1955 and 1959 of the ABC/Desilu television series \"The Life and Legend of Wyatt Earp\", starring Hugh O'Brian in the title role of the frontier marshal Wyatt Earp.","title":""},{"docid":"42767819","text":"Americo Zorilla \"Rico\" Alaniz (October 25, 1919 – March 9, 2015) was a Mexican-born American actor in film and television best known for his role of the peaceful Cheyenne informer \"Mr. Cousin\" in sixteen episodes from 1955 to 1959 of the ABC/Desilu western television series, \"The Life and Legend of Wyatt Earp\", with Hugh O'Brian in the title role as deputy Marshal Wyatt Earp.","title":""},{"docid":"2233445","text":"Trevor Bardette (November 19, 1902 – November 28, 1977) was an American film and television actor. He appeared in several memorable episodes of \"Adventures of Superman\" and as Newman Haynes Clanton, or Old Man Clanton, in 21 episodes of the ABC/Desilu western series, \"The Life and Legend of Wyatt Earp.\"","title":""},{"docid":"42694161","text":"William Tannen (November 17, 1911 – December 2, 1976) was an American actor originally from New York City, who was best known for his role of Deputy Hal Norton in fifty-six episodes from 1956 to 1958 of the ABC/Desilu western television series, \"The Life and Legend of Wyatt Earp\", with Hugh O'Brian as Deputy Marshal Wyatt Earp.","title":""},{"docid":"3039544","text":"Wyatt Earp is a 1994 American semi-biographical Western film directed by Lawrence Kasdan and co-written by Kasdan and Dan Gordon. It stars Kevin Costner in the title role as lawman Wyatt Earp, and features an ensemble cast that includes Gene Hackman, Mark Harmon, Michael Madsen, Bill Pullman, Dennis Quaid, Isabella Rossellini, Tom Sizemore, JoBeth Williams, and Mare Winningham.","title":""},{"docid":"40501707","text":"Voodoo Tiger (1952) is the ninth Jungle Jim film produced by Columbia Pictures. It features Johnny Weissmuller in his ninth performance as the protagonist adventurer Jungle Jim, and James Seay as the film's antagonist. Jean Byron also stars. The film was directed by Spencer G. Bennet and written by Samuel Newman.","title":""},{"docid":"32035024","text":"Wyatt Earp's Revenge is a 2012 American Western film about the legendary lawman Wyatt Earp. It is a fictionalized account of an actual Old West event, the slaying of beautiful singer Dora Hand in Dodge City, Kansas, when Earp was a deputy there. In one of its many instances of dramatic license, the movie depicts Hand as Earp's sweetheart. The film's framing device is a reporter's interview with an aging Earp, who reminisces about the tragedy. (Val Kilmer plays the older Earp, while Shawn Roberts plays the younger one.) The film was released on March 6, 2012, in the United States. The film was produced by Jeff Schenck and Barry Barnholtz and directed by Michael Feifer. The screenplay was written by Darren Benjamin Shepherd.","title":""},{"docid":"643710","text":"Michael Søren Madsen (born September 25, 1958) is an American actor, producer, director, writer, poet and photographer. He has starred in over 200 films, including \"Thelma & Louise\", \"Reservoir Dogs\", \"Wyatt Earp\", \"Free Willy\", \"Species\", \"Donnie Brasco\", \"Sin City\", \"Kill Bill\", \"The Hateful Eight\" and many direct-to-video films. He has also guest starred in numerous television series and has done voice work in several video games. Madsen is known for making many films with Quentin Tarantino.","title":""},{"docid":"9426146","text":"Frontier Marshal is a 1939 western film directed by Allan Dwan and starring Randolph Scott as Wyatt Earp. The movie is the second film produced by Sol M. Wurtzel based on Stuart N. Lake's biography of Earp, \"\" (later found to be largely fictionalized). An earlier version was Wurtzel's \"Frontier Marshal\", filmed in 1934. A later version of the story was filmed by John Ford in 1946, \"My Darling Clementine\", which included whole scenes reshot from the 1939 film.","title":""},{"docid":"6592954","text":"Celia Ann \"Mattie\" Blaylock (January 1850 – July 3, 1888) was a prostitute who became the romantic companion and common-law wife of Old West lawman and gambler Wyatt Earp for about eight years. Knowledge of her place in Wyatt's life was concealed by Josephine Earp, his later common-law wife, who worked hard to protect her and Wyatt's reputation in their later years.","title":""},{"docid":"40389243","text":"Devil Goddess (1955) is the sixteenth and final Jungle Jim film produced by Columbia Pictures. It features Johnny Weissmuller in his third and last performance as the protagonist adventurer Johnny Weissmuller (a character previously called \"Jungle Jim\") and Ed Hinton and William Tannen as the film's antagonists, Leopold and Nels Comstock, respectively. Angela Stevens also stars. The film was directed by Spencer G. Bennet and written by Dwight Babcock and George H. Plympton.","title":""},{"docid":"2160135","text":"Tombstone: The Town Too Tough to Die is a 1942 Western film directed by William McGann and starring Richard Dix as Wyatt Earp, Kent Taylor as Doc Holliday and Edgar Buchanan as Curly Bill Brocious. The supporting cast of this movie about the gunfight at the OK Corral also features Rex Bell as Virgil Earp and Victor Jory as Ike Clanton.","title":""},{"docid":"47983208","text":"Jewels of Brandenburg is a 1947 American crime film directed by Eugene Forde and written by Irving Cummings Jr. and Robert G. North. The film stars Richard Travis, Micheline Cheirel, Leonard Strong, Carol Thurston, Lewis Russell and Louis Mercier. The film was released on May 27, 1947, by 20th Century Fox.","title":""},{"docid":"6592405","text":"Warren Baxter Earp (March 9, 1855 – July 6, 1900) was the youngest brother of Wyatt, Morgan, Virgil, James, and Newton Earp. Although he was not present during the Gunfight at the O.K. Corral, after Virgil was maimed in an ambush, Warren joined Wyatt and was in town when Morgan was assassinated. He also helped Wyatt in the hunt for the outlaws they believed responsible. Later in life, Warren developed a reputation as a bully and was killed in an argument in 1900.","title":""},{"docid":"4052442","text":"Sunset is a 1988 American mystery action film written and directed by Blake Edwards and starring Bruce Willis as legendary Western actor Tom Mix, who teams up with legendary lawman Wyatt Earp, portrayed for the second time in a theatrical film by James Garner. Based on an unpublished novel by Rod Amateau, the plot has Mix and Earp team up to solve a murder in Hollywood in 1929.","title":""},{"docid":"1483025","text":"Gunfight at the O.K. Corral is a 1957 American western film starring Burt Lancaster as Wyatt Earp and Kirk Douglas as Doc Holliday, based on a real event which took place on October 26, 1881. The picture was directed by John Sturges from a screenplay written by novelist Leon Uris.","title":""},{"docid":"47278547","text":"Riders of the Frontier, also known as Ridin' the Frontier, is a 1939 American western film directed by Spencer Gordon Bennet and starring Tex Ritter and Jack Rutherford. It is a remake of the 1936 film \"The Cattle Thief\".","title":""},{"docid":"44172999","text":"Shark River is a 1953 American Florida Western adventure film directed by John Rawlins and written by Louis Lantz and Lewis Meltzer. It stars Steve Cochran, Carole Mathews, Warren Stevens, Robert Cunningham, Ruth Foreman, Spencer Fox and Bill Piper, and was released on November 13, 1953, by United Artists.","title":""},{"docid":"1558601","text":"Hugh O'Brian (born Hugh Charles Krampe; April 19, 1925 – September 5, 2016) was an American actor and humanitarian, best known for his starring roles in the ABC western television series \"The Life and Legend of Wyatt Earp\" (1955–1961) and the NBC action television series \"Search\" (1972–1973), as well as films including the Agatha Christie adaptation \"Ten Little Indians\" (1965); he also had a notable supporting role in John Wayne's last film, \"The Shootist\" (1976). He was highly regarded for creating the Hugh O'Brian Youth Leadership Foundation, a non-profit youth leadership development program for high school scholars which has sponsored over 400,000 students since he founded the program in 1958 following an extended visit with Nobel Peace Prize-winning theologian and physician Albert Schweitzer.","title":""},{"docid":"5455247","text":"Hour of the Gun is a 1967 Western film depicting Wyatt Earp and Doc Holliday during their 1881 battles against Ike Clanton and his brothers in the Gunfight at the O.K. Corral, and the gunfight's aftermath in and around Tombstone, Arizona, starring James Garner as Earp, Jason Robards as Holliday, and Robert Ryan as Clanton. The movie was directed by John Sturges.","title":""},{"docid":"31925499","text":"The 1976 book I Married Wyatt Earp was believed to be a memoir of his widow Josephine Earp, but was many years later described as a fraud, creative exercise, and a hoax. Originally published by the respected University of Arizona Press, it is the second best-selling book about western Deputy U.S. Marshal Wyatt Earp ever sold. It was regarded for many years as a factual account that shed considerable light on the life of Wyatt Earp and his brothers in Tombstone, Arizona Territory. It was cited in scholarly works, assigned as classroom work, and used as a source by filmmakers. Amateur Earp historian Glenn Boyer said that the retouched image on the cover of a scantily-clad woman was of Josephine in her 20s, and based on his statements, copies of the image were later sold at auction for up to $2,875.","title":""},{"docid":"11192988","text":"Paul Brinegar (December 19, 1917 – March 27, 1995) was an American character actor best known for his roles in three western series: \"The Life and Legend of Wyatt Earp\", \"Rawhide\", and \"Lancer\".","title":""},{"docid":"38578122","text":"Glenn G. Boyer (January 5, 1924 - February 14, 2013) was a controversial author who published three books and a number of articles about Wyatt Earp and related figures in the American Old West. He was the first person to reveal the existence of Wyatt Earp's second wife, Mattie Blaylock. His publications were for many years regarded as the authoritative source on Wyatt Earp's life. However, when other experts began to seek evidence supporting Boyer's work, he would or could not prove the existence of documents that he said he owned and had cited as essential sources. In one case, an individual he cited as a key source was exposed as a complete fabrication. His reputation and the authenticity of his work was seriously damaged. Although he retained many supporters, his work became surrounded by controversy.","title":""},{"docid":"3214830","text":"John Maxwell (March 11, 1918 Spokane, Washington – July 18, 1982) was an American film and television actor who appeared in over 100 films of the 1940s and 1950s. Many times the actor appeared in films uncredited. Occasionally he played larger roles in movies, such as in \"The Prowler\". He was born in Spokane, Washington. His television guest appearances included \"The Lone Ranger\", \"Lassie\", \"The Life and Legend of Wyatt Earp\", \"The Rifleman\" and \"Bonanza\".","title":""}],"string":"[\n {\n \"docid\": \"42773781\",\n \"text\": \"Jimmy Noel (May 15, 1903–January 31, 1985) was a Massachusetts-born actor and stuntman who appeared in hundreds of largely uncredited roles in film and television between 1949 and 1975. He appeared 202 times on CBS's western series, \\\"Gunsmoke\\\", starring James Arness, and in 144 episodes of the ABC/Desilu production, \\\"The Life and Legend of Wyatt Earp\\\", with Hugh O'Brian in the title role of deputy Marshal Wyatt Earp. Buddy Roosevelt made similar appearances in sixty-five \\\"Wyatt Earp\\\" episodes.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"16537645\",\n \"text\": \"Frederick Hazlitt Brennan (September 23, 1901 – June 30, 1962) was an American screenwriter of more than thirty films between 1929 and 1953 and the director of the ABC/Desilu western television series, \\\"The Life and Legend of Wyatt Earp\\\" (1955-1961), starring Hugh O'Brian as deputy Marshal Wyatt Earp.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"1998796\",\n \"text\": \"The Life and Legend of Wyatt Earp is the first western television series written for adults, premiering four days before \\\"Gunsmoke\\\" on September 6, 1955. It is loosely based on the life of frontier marshal Wyatt Earp. The half-hour black-and-white program aired for 6 seasons (229 episodes) on ABC from 1955 to 1961 and featured Hugh O'Brian in the title role.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"36406131\",\n \"text\": \"Wyatt Earp: Return to Tombstone is a 1994 independent film starring Hugh O'Brian as Wyatt Earp, featuring new footage mixed with colorized sequences from O'Brian's 1955-1961 television series \\\"The Life and Legend of Wyatt Earp\\\". The supporting cast for the new footage includes Bruce Boxleitner, Paul Brinegar, Harry Carey, Jr., Bo Hopkins, and Don Meredith. The colorized flashback archival footage from the original television series features Douglas Fowley as Doc Holliday and Lloyd Corrigan as Ned Buntline. The movie was directed by Paul Landres and Frank McDonald.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"42543113\",\n \"text\": \"Raymond C. Boyle, known as Ray Boyle or as the screen name Dirk London (born June 28, 1925), is an American actor known principally for his sporadic role as Morgan Earp, the brother of Wyatt Earp in fifteen episodes of the ABC/Desilu Productions western television series, \\\"The Life and Legend of Wyatt Earp,\\\" starring Hugh O'Brian in the title role. Boyle's episodes began with \\\"The Assassins\\\" in 1956 and ended with \\\"The Outlaws Cry Murder\\\" in 1961.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"23440679\",\n \"text\": \"Carol Montgomery Stone (February 1, 1915 – June 10, 2011) was an actress who played \\\"Big Nose Kate\\\", or Kate Holliday, the common law wife of Doc Holliday, in ten episodes in the 1957-1958 season of the ABC/Desilu western television series, \\\"The Life and Legend of Wyatt Earp\\\".\",\n \"title\": \"\"\n },\n {\n \"docid\": \"39941754\",\n \"text\": \"Mason Alan Dinehart (born April 30, 1936), also known as Mason Alan Dinehart III, Alan Dinehart III, or Mase Dinehart, is an American businessman and former actor best known for his role as a youthful Bat Masterson in thirty-four episodes between 1955 and 1959 of the ABC/Desilu television series \\\"The Life and Legend of Wyatt Earp\\\", starring Hugh O'Brian in the title role of the frontier marshal Wyatt Earp.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"42767819\",\n \"text\": \"Americo Zorilla \\\"Rico\\\" Alaniz (October 25, 1919 – March 9, 2015) was a Mexican-born American actor in film and television best known for his role of the peaceful Cheyenne informer \\\"Mr. Cousin\\\" in sixteen episodes from 1955 to 1959 of the ABC/Desilu western television series, \\\"The Life and Legend of Wyatt Earp\\\", with Hugh O'Brian in the title role as deputy Marshal Wyatt Earp.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"2233445\",\n \"text\": \"Trevor Bardette (November 19, 1902 – November 28, 1977) was an American film and television actor. He appeared in several memorable episodes of \\\"Adventures of Superman\\\" and as Newman Haynes Clanton, or Old Man Clanton, in 21 episodes of the ABC/Desilu western series, \\\"The Life and Legend of Wyatt Earp.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"42694161\",\n \"text\": \"William Tannen (November 17, 1911 – December 2, 1976) was an American actor originally from New York City, who was best known for his role of Deputy Hal Norton in fifty-six episodes from 1956 to 1958 of the ABC/Desilu western television series, \\\"The Life and Legend of Wyatt Earp\\\", with Hugh O'Brian as Deputy Marshal Wyatt Earp.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"3039544\",\n \"text\": \"Wyatt Earp is a 1994 American semi-biographical Western film directed by Lawrence Kasdan and co-written by Kasdan and Dan Gordon. It stars Kevin Costner in the title role as lawman Wyatt Earp, and features an ensemble cast that includes Gene Hackman, Mark Harmon, Michael Madsen, Bill Pullman, Dennis Quaid, Isabella Rossellini, Tom Sizemore, JoBeth Williams, and Mare Winningham.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"40501707\",\n \"text\": \"Voodoo Tiger (1952) is the ninth Jungle Jim film produced by Columbia Pictures. It features Johnny Weissmuller in his ninth performance as the protagonist adventurer Jungle Jim, and James Seay as the film's antagonist. Jean Byron also stars. The film was directed by Spencer G. Bennet and written by Samuel Newman.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"32035024\",\n \"text\": \"Wyatt Earp's Revenge is a 2012 American Western film about the legendary lawman Wyatt Earp. It is a fictionalized account of an actual Old West event, the slaying of beautiful singer Dora Hand in Dodge City, Kansas, when Earp was a deputy there. In one of its many instances of dramatic license, the movie depicts Hand as Earp's sweetheart. The film's framing device is a reporter's interview with an aging Earp, who reminisces about the tragedy. (Val Kilmer plays the older Earp, while Shawn Roberts plays the younger one.) The film was released on March 6, 2012, in the United States. The film was produced by Jeff Schenck and Barry Barnholtz and directed by Michael Feifer. The screenplay was written by Darren Benjamin Shepherd.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"643710\",\n \"text\": \"Michael Søren Madsen (born September 25, 1958) is an American actor, producer, director, writer, poet and photographer. He has starred in over 200 films, including \\\"Thelma & Louise\\\", \\\"Reservoir Dogs\\\", \\\"Wyatt Earp\\\", \\\"Free Willy\\\", \\\"Species\\\", \\\"Donnie Brasco\\\", \\\"Sin City\\\", \\\"Kill Bill\\\", \\\"The Hateful Eight\\\" and many direct-to-video films. He has also guest starred in numerous television series and has done voice work in several video games. Madsen is known for making many films with Quentin Tarantino.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"9426146\",\n \"text\": \"Frontier Marshal is a 1939 western film directed by Allan Dwan and starring Randolph Scott as Wyatt Earp. The movie is the second film produced by Sol M. Wurtzel based on Stuart N. Lake's biography of Earp, \\\"\\\" (later found to be largely fictionalized). An earlier version was Wurtzel's \\\"Frontier Marshal\\\", filmed in 1934. A later version of the story was filmed by John Ford in 1946, \\\"My Darling Clementine\\\", which included whole scenes reshot from the 1939 film.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"6592954\",\n \"text\": \"Celia Ann \\\"Mattie\\\" Blaylock (January 1850 – July 3, 1888) was a prostitute who became the romantic companion and common-law wife of Old West lawman and gambler Wyatt Earp for about eight years. Knowledge of her place in Wyatt's life was concealed by Josephine Earp, his later common-law wife, who worked hard to protect her and Wyatt's reputation in their later years.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"40389243\",\n \"text\": \"Devil Goddess (1955) is the sixteenth and final Jungle Jim film produced by Columbia Pictures. It features Johnny Weissmuller in his third and last performance as the protagonist adventurer Johnny Weissmuller (a character previously called \\\"Jungle Jim\\\") and Ed Hinton and William Tannen as the film's antagonists, Leopold and Nels Comstock, respectively. Angela Stevens also stars. The film was directed by Spencer G. Bennet and written by Dwight Babcock and George H. Plympton.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"2160135\",\n \"text\": \"Tombstone: The Town Too Tough to Die is a 1942 Western film directed by William McGann and starring Richard Dix as Wyatt Earp, Kent Taylor as Doc Holliday and Edgar Buchanan as Curly Bill Brocious. The supporting cast of this movie about the gunfight at the OK Corral also features Rex Bell as Virgil Earp and Victor Jory as Ike Clanton.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"47983208\",\n \"text\": \"Jewels of Brandenburg is a 1947 American crime film directed by Eugene Forde and written by Irving Cummings Jr. and Robert G. North. The film stars Richard Travis, Micheline Cheirel, Leonard Strong, Carol Thurston, Lewis Russell and Louis Mercier. The film was released on May 27, 1947, by 20th Century Fox.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"6592405\",\n \"text\": \"Warren Baxter Earp (March 9, 1855 – July 6, 1900) was the youngest brother of Wyatt, Morgan, Virgil, James, and Newton Earp. Although he was not present during the Gunfight at the O.K. Corral, after Virgil was maimed in an ambush, Warren joined Wyatt and was in town when Morgan was assassinated. He also helped Wyatt in the hunt for the outlaws they believed responsible. Later in life, Warren developed a reputation as a bully and was killed in an argument in 1900.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"4052442\",\n \"text\": \"Sunset is a 1988 American mystery action film written and directed by Blake Edwards and starring Bruce Willis as legendary Western actor Tom Mix, who teams up with legendary lawman Wyatt Earp, portrayed for the second time in a theatrical film by James Garner. Based on an unpublished novel by Rod Amateau, the plot has Mix and Earp team up to solve a murder in Hollywood in 1929.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"1483025\",\n \"text\": \"Gunfight at the O.K. Corral is a 1957 American western film starring Burt Lancaster as Wyatt Earp and Kirk Douglas as Doc Holliday, based on a real event which took place on October 26, 1881. The picture was directed by John Sturges from a screenplay written by novelist Leon Uris.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"47278547\",\n \"text\": \"Riders of the Frontier, also known as Ridin' the Frontier, is a 1939 American western film directed by Spencer Gordon Bennet and starring Tex Ritter and Jack Rutherford. It is a remake of the 1936 film \\\"The Cattle Thief\\\".\",\n \"title\": \"\"\n },\n {\n \"docid\": \"44172999\",\n \"text\": \"Shark River is a 1953 American Florida Western adventure film directed by John Rawlins and written by Louis Lantz and Lewis Meltzer. It stars Steve Cochran, Carole Mathews, Warren Stevens, Robert Cunningham, Ruth Foreman, Spencer Fox and Bill Piper, and was released on November 13, 1953, by United Artists.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"1558601\",\n \"text\": \"Hugh O'Brian (born Hugh Charles Krampe; April 19, 1925 – September 5, 2016) was an American actor and humanitarian, best known for his starring roles in the ABC western television series \\\"The Life and Legend of Wyatt Earp\\\" (1955–1961) and the NBC action television series \\\"Search\\\" (1972–1973), as well as films including the Agatha Christie adaptation \\\"Ten Little Indians\\\" (1965); he also had a notable supporting role in John Wayne's last film, \\\"The Shootist\\\" (1976). He was highly regarded for creating the Hugh O'Brian Youth Leadership Foundation, a non-profit youth leadership development program for high school scholars which has sponsored over 400,000 students since he founded the program in 1958 following an extended visit with Nobel Peace Prize-winning theologian and physician Albert Schweitzer.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"5455247\",\n \"text\": \"Hour of the Gun is a 1967 Western film depicting Wyatt Earp and Doc Holliday during their 1881 battles against Ike Clanton and his brothers in the Gunfight at the O.K. Corral, and the gunfight's aftermath in and around Tombstone, Arizona, starring James Garner as Earp, Jason Robards as Holliday, and Robert Ryan as Clanton. The movie was directed by John Sturges.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"31925499\",\n \"text\": \"The 1976 book I Married Wyatt Earp was believed to be a memoir of his widow Josephine Earp, but was many years later described as a fraud, creative exercise, and a hoax. Originally published by the respected University of Arizona Press, it is the second best-selling book about western Deputy U.S. Marshal Wyatt Earp ever sold. It was regarded for many years as a factual account that shed considerable light on the life of Wyatt Earp and his brothers in Tombstone, Arizona Territory. It was cited in scholarly works, assigned as classroom work, and used as a source by filmmakers. Amateur Earp historian Glenn Boyer said that the retouched image on the cover of a scantily-clad woman was of Josephine in her 20s, and based on his statements, copies of the image were later sold at auction for up to $2,875.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"11192988\",\n \"text\": \"Paul Brinegar (December 19, 1917 – March 27, 1995) was an American character actor best known for his roles in three western series: \\\"The Life and Legend of Wyatt Earp\\\", \\\"Rawhide\\\", and \\\"Lancer\\\".\",\n \"title\": \"\"\n },\n {\n \"docid\": \"38578122\",\n \"text\": \"Glenn G. Boyer (January 5, 1924 - February 14, 2013) was a controversial author who published three books and a number of articles about Wyatt Earp and related figures in the American Old West. He was the first person to reveal the existence of Wyatt Earp's second wife, Mattie Blaylock. His publications were for many years regarded as the authoritative source on Wyatt Earp's life. However, when other experts began to seek evidence supporting Boyer's work, he would or could not prove the existence of documents that he said he owned and had cited as essential sources. In one case, an individual he cited as a key source was exposed as a complete fabrication. His reputation and the authenticity of his work was seriously damaged. Although he retained many supporters, his work became surrounded by controversy.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"3214830\",\n \"text\": \"John Maxwell (March 11, 1918 Spokane, Washington – July 18, 1982) was an American film and television actor who appeared in over 100 films of the 1940s and 1950s. Many times the actor appeared in films uncredited. Occasionally he played larger roles in movies, such as in \\\"The Prowler\\\". He was born in Spokane, Washington. His television guest appearances included \\\"The Lone Ranger\\\", \\\"Lassie\\\", \\\"The Life and Legend of Wyatt Earp\\\", \\\"The Rifleman\\\" and \\\"Bonanza\\\".\",\n \"title\": \"\"\n }\n]"}}},{"rowIdx":188,"cells":{"query_id":{"kind":"string","value":"PLAIN-2203"},"query":{"kind":"string","value":"Taiwan"},"positive_passages":{"kind":"list like","value":[{"docid":"MED-1959","text":"Since 1991 the US Department of Agriculture (USDA) has conducted annual surveys of pesticide residues in foods under the Agricultural Marketing Service's Pesticide Data Program (PDP). To assess chemical residues in domestically marketed catfish products, 1479 catfish samples were collected during the 2008-2010 PDPs. A subset of 202 samples was analysed for 17 toxic polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs). The average pattern of the individual PCDD/F congener concentrations in the catfish was rather unique in that it had almost no measurable amounts of polychlorinated dibenzofurans (PCDFs), but all PCDDs were present. This pattern was more dominant in the domestically produced catfish products than in the imported products (China/Taiwan). Comparison of the pattern to known sources of PCDD/Fs showed strong similarities to the pattern of PCDD/Fs found in kaolin clays which have often been used as anti-caking agents in animal feeds. To investigate whether catfish feeds may be the source of the PCDD/Fs found in the catfish, archived catfish feed data from a US Food and Drug Administration (USFDA) database were examined. In 61 out of 112 feed samples, the PCDD concentrations were 50 times higher than the PCDF concentrations and resembled the pattern found in the catfish products and in clays mined in the south-eastern United States. Although the source of PCDD/Fs in domestically marketed catfish products cannot be definitively established, mined clay products used in feeds should be considered a likely source and, given the wide concentration range of PCDD/Fs that has been found in clays, a critical control point for PCDD/Fs entrance to the food supply.","title":"Dioxin congener patterns in commercial catfish from the United States and the indication of mineral clays as the potential source."},{"docid":"MED-2179","text":"OBJECTIVE: To investigate the association between cooking behaviour and long-term survival among elderly Taiwanese. DESIGN: Cohort study. The duration of follow-up was the interval between the date of interview and the date of death or 31 December 2008, when censored for survivors. Information used included demographics, socio-economic status, health behaviours, cooking frequencies, physical function, cognitive function, nutrition knowledge awareness, eating out habits and food and nutrient intakes. These data were linked to death records. Cox proportional-hazards models were used to evaluate cooking frequency on death from 1999 to 2008 with related covariate adjustments. SETTING: Elderly Nutrition and Health Survey in Taiwan, 1999-2000. SUBJECTS: Nationally representative free-living elderly people aged ≥65 years (n 1888). RESULTS: During a 10-year follow-up, 695 participants died. Those who cooked most frequently were younger, women, unmarried, less educated, non-drinkers of alcohol, non-smokers, without chewing difficulty, had spouse as dinner companion, normal cognition, who walked or shopped more than twice weekly, who ate less meat and more vegetables. Highly frequent cooking (>5 times/week, compared with never) predicted survival (hazard ratio (HR) = 0·47; 95 % CI, 0·36, 0·61); with adjustment for physical function, cognitive function, nutrition knowledge awareness and other covariates, HR was 0·59 (95 % CI, 0·41, 0·86). Women benefited more from cooking more frequently than did men, with decreased HR, 51 % v. 24 %, when most was compared with least. A 2-year delay in the assessment of survivorship led to similar findings. CONCLUSIONS: Cooking behaviour favourably predicts survivorship. Highly frequent cooking may favour women more than men.","title":"Cooking frequency may enhance survival in Taiwanese elderly."},{"docid":"MED-2311","text":"BACKGROUND: The association between fruit and vegetable (FV) consumption and overall mortality has seldom been investigated in large cohort studies. Findings from the few available studies are inconsistent. OBJECTIVE: The objective was to examine the dose-response relation between FV consumption and mortality, in terms of both time and rate, in a large prospective cohort of Swedish men and women. DESIGN: FV consumption was assessed through a self-administrated questionnaire in a population-based cohort of 71,706 participants (38,221 men and 33,485 women) aged 45-83 y. We performed a dose-response analysis to evaluate 10th survival percentile differences (PDs) by using Laplace regression and estimated HRs by using Cox regression. RESULTS: During 13 y of follow-up, 11,439 deaths (6803 men and 4636 women) occurred in the cohort. In comparison with 5 servings FV/d, a lower consumption was progressively associated with shorter survival and higher mortality rates. Those who never consumed FV lived 3 y shorter (PD: -37 mo; 95% CI: -58, -16 mo) and had a 53% higher mortality rate (HR: 1.53; 95% CI: 1.19, 1.99) than did those who consumed 5 servings FV/d. Consideration of fruit and vegetables separately showed that those who never consumed fruit lived 19 mo shorter (PD: -19 mo; 95% CI: -29, -10 mo) than did those who ate 1 fruit/d. Participants who consumed 3 vegetables/d lived 32 mo longer than did those who never consumed vegetables (PD: 32 mo; 96% CI: 13, 51 mo). CONCLUSION: FV consumption <5 servings/d is associated with progressively shorter survival and higher mortality rates. The Swedish Mammography Cohort and the Cohort of Swedish Men were registered at clinicaltrials.gov as NCT01127698 and NCT01127711, respectively.","title":"Fruit and vegetable consumption and all-cause mortality: a dose-response analysis."},{"docid":"MED-1958","text":"Food, especially meat, milk, and fish, is the immediate source of almost all polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and dioxinlike compounds in the general population. To estimate intake of these highly toxic compounds, we performed congener-specific dioxin analyses for the first time on U.S. food for 18 dairy meat, and fish samples from a supermarket in upstate New York. 2,3,7,8 Tetrachlorodibenzo-p-dioxin (TCDD, \"dioxin\") toxic equivalents (TEqs) on a wet weight basis for the dairy products ranged for 0.04 to 0.7 ppt, meat TEqs ranged from 0.03 to 1.5 ppt, and fish TEqs ranged from 0.02 to 0.13 ppt. Previous human breast milk and infant formula analyses were used with the current preliminary food data to estimate a range of dioxin intake for Americans. Average daily food intake of TEqs for an adult weighing 65 kg was estimated to be between 0.3 and 3.0 pg/kg body weight, for a total of 18-192 pg TEq, using 1986 American consumption rates. Due to the relatively high level of PCDDs and PCDFs commonly found in human breast milk from American women and from women in other industrial countries, a nursing infant may consume an average of 35-53 pg TEq/kg body weight/day in its first year of life. This may be compared with the current U.S. EPA virtually safe dose of 0.006 pg TCDD/kg body weight per day over a 70-year lifetime based on an upper limit cancer risk of 10(-6), or the 10 pg/kg/day used by some European government agencies.","title":"Congener-specific levels of dioxins and dibenzofurans in U.S. food and estimated daily dioxin toxic equivalent intake."},{"docid":"MED-1963","text":"In 1994, we analyzed 43 foodstuff samples from local supermarkets in southern Mississippi, USA, for PCDD/PCDF. 2,3,7,8-Cl4DD could be quantified in 31 of these samples. On a lipid basis, levels in meat (0.53-1.10 pg I-TEQ/g) and dairy products (0.42-1.10 pg I-TEQ/g) were slightly lower than those reported from other industrialized countries. While levels in dairy samples from the United States and Europe are comparable, there is a difference in the contribution of individual congeners to the I-TEQ: for example, in milk samples from Germany approximately 40% of the I-TEQ is due to the presence of 2,3, 4,7,8-Cl5DF while in the Mississippi samples this congener only contributes 16%. The highest concentrations of PCDD/PCDF in our study were detected in the farm-raised catfish (10.2-27.8 pg I-TEQ/g). A unique finding was that in addition to the 2,3,7,8-substituted PCDD/PCDF the catfish samples contained many non-2,3,7,8-substituted congeners. This is unusual because vertebrate animals selectively eliminate or metabolize the non-2,3,7,8-substituted congeners.","title":"Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/PCDF) in food samples collected in southern Mississippi, USA."},{"docid":"MED-1962","text":"The concentrations of the 2,3,7,8-Cl substituted dibenzo-p-dioxins/-furans (PCDDs/PCDFs) were determined in the edible tissues of whole chicken fryers and compared with the values found in their abdominal fat. The values are presented both on a whole weight basis and on a lipid adjusted basis for each tissue. While there is a marked difference in the concentration of the 2,3,7,8-dibenzo-p-dioxins in the edible tissues expressed on a whole weight basis, the lipid-adjusted concentrations of the individual dioxins were not statistically different in the various tissues. This validates the use of lipid adjusted concentrations of 2,3,7,8-PCDDs/PCDFs in abdominal fat for the determination of the presence of these compounds in different tissues.","title":"The concentration and distribution of 2,3,7,8-dibenzo-p-dioxins/-furans in chickens."},{"docid":"MED-2182","text":"Over the past century, a major shift in North American food practices has been taking place. However, the literature on this topic is lacking in several areas. Some available research on food and cooking practices in the current context is presented, with a focus on how these are affecting health and how they might be contributing to health inequalities within the population. First, cooking and cooking skills are examined, along with the ambiguities related to terms associated with cooking in the research literature. Food choice, cooking, and health are described, particularly in relation to economic factors that may lead to health inequalities within the population. The importance of developing an understanding of factors within the wider food system as part of food choice and cooking skills is presented, and gaps in the research literature are examined and areas for future research are presented. Cooking practices are not well studied but are important to an understanding of human nutritional health as it relates to cultural, environmental, and economic factors.","title":"Food, cooking skills, and health: a literature review."},{"docid":"MED-1957","text":"One combined catfish feed sample from Arkansas, USA, and its eight ingredients were analyzed for PCDDs and PCDFs. One of the ingredients, soybean meal, was highly contaminated by PCDDs, especially the toxic 2,3,7,8-substituted congeners, e.g., 7.3 pg/g dry weight or 370 pg/g lipid for the 2,3,7,8-tetra CDD. The I-TEQ value for the soybean meal was 11.4 pg/g dry weight or 576 pg/g fat. The corresponding values for the combined catfish feed concentrations were approximately 3 times lower. The congener pattern, the congener profile and the ratio sigma PCDDs/sigma PCDFs for the soybean meal were quite unique. We are not aware of any environmental sample or technical product with similar characteristics. As a result, natural formation of the PCDDs found in the soybean meal cannot be ruled out.","title":"PCDD and PCDF contamination in catfish feed from Arkansas, USA."},{"docid":"MED-2310","text":"OBJECTIVES To examine the relationship between fruit and vegetable intake, physical activity, and all-cause mortality in older women. DESIGN Six Cox proportional hazards models examined independent and additive relationships between physical activity, carotenoids, and all-cause mortality. Additional models tested whether physical activity and carotenoids were conjointly related to mortality. Models were adjusted for age, education, and race and ethnicity. SETTING Baltimore, Maryland. PARTICIPANTS Seven hundred thirteen women aged 70 to 79 participating in the Women’s Health and Aging Studies. MEASUREMENTS Total serum carotenoids, a marker of fruit and vegetable intake, and physical activity were measured at baseline. Physical activity was measured according to kilocalorie expenditure. RESULTS During 5 years of follow-up, 82 (11.5%) participants died. Measured continuously, physical activity improved survival (HR = 0.52, 95% CI = 0.41–0.66, P < .001). The most active women were more likely to survive than the least physically active women (HR = 0.28, 95% CI = 0.13–0.59, P < .001). Continuous measures of carotenoids improved survival (HR = 0.67, 95% CI = 0.51–0.89, P = .01). Women in the highest tertile of total carotenoids were more likely to survive those in the lowest (HR = 0.50, 95% CI = 0.27–0.91, P = .03). When examined in the same model, continuous measures of physical activity (HR = 0.54, 95% CI = 0.42–0.68, P < .001) and carotenoids (HR = 0.76, 95% CI = 0.59–0.98, P = .04) predicted survival during follow-up. CONCLUSION The combination of low total serum carotenoids and low physical activity, both modifiable risk factors, strongly predicted earlier mortality. These findings provide preliminary support that higher fruit and vegetable intake and exercise improve survival.","title":"Fruit and Vegetable Intake, Physical Activity, and Mortality in Older Community-Dwelling Women"},{"docid":"MED-1961","text":"Dioxins and related compounds are undesirable and unintended contaminants in the food supply, and dietary intake is the major route of exposure. Reducing dietary exposure to dioxins among the most vulnerable segments of the population (i.e., pregnant women, infants, and young girls) is an effective strategy for reducing body burdens in future generations. Exposure to dioxins through foods can be minimized by selecting lower-fat versions of meats, poultry, and dairy products. Consuming all foods, including fatty fish, in recommended amounts is congruent with the goal of reducing dioxin intake exposure and maintaining good health.","title":"Reducing exposure to dioxins and related compounds through foods in the next generation."},{"docid":"MED-1541","text":"We propose the hypothesis that a vegetarian diet reduces the risk of developing diabetes. Findings that have generated this hypothesis are from a population of 25,698 adult White Seventh-day Adventists identified in 1960. During 21 years of follow-up, the risk of diabetes as an underlying cause of death in Adventists was approximately one-half the risk for all US Whites. Within the male Adventist population, vegetarians had a substantially lower risk than non-vegetarians of diabetes as an underlying or contributing cause of death. Within both the male and female Adventist populations, the prevalence of self-reported diabetes also was lower in vegetarians than in non-vegetarians. The associations observed between diabetes and meat consumption were apparently not due to confounding by over- or under-weight, other selected dietary factors, or physical activity. All of the associations between meat consumption and diabetes were stronger in males than in females.","title":"Does a vegetarian diet reduce the occurrence of diabetes?"},{"docid":"MED-2181","text":"Background Little is known about the impact of location of food consumption and preparation upon daily energy intake for children. Objective To examine trends in daily energy intake by children for foods eaten at home or away-from-home, by source of preparation, and for combined categories of eating location and food source. Subjects The analysis uses data from 29,217 children aged 2–18 years from the 1977–1978 Nationwide Food Consumption Survey, 1989–1991 and 1994–1998 Continuing Survey of Food Intake by Individuals, and 2003–2006 National Health and Nutrition Examination Surveys. Methods Nationally representative weighted percentages and means of daily energy intake by eating location were analyzed for trends from 1977 to 2006. Comparisons by food source were examined from 1994 to 2006. Analyses were repeated for 3 age groups: 2–6, 7–12, and 13–18 year olds. Difference testing was conducted using a t test. Results Increased energy intake (+179 kcal/d) by children from 1977–2006 was associated with a major increase in calories eaten away-from-home (+255 kcal/d). The percentage of kcal/d eaten away-from-home increased from 23.4% to 33.9% from 1977–2006. No further increase was observed from 1994–2006, but the sources of calories shifted. The percentage of calories from fast food increased to surpass intake from schools and become the largest contributor to foods prepared away-from-home for all age groups. For foods eaten away-from-home, the percentage of kcal/d from stores increased to become the largest source of calories eaten away-from-home. Fast food eaten at home and store-bought food eaten away-from-home increased significantly. Conclusion Eating location and food source significantly impact daily energy intake for children. Foods prepared away-from-home, including fast food eaten at home and store-prepared food eaten away-from-home, are fueling the increase in total calorie intake. However, further research using alternative data sources is necessary to verify that store-bought foods eaten away-from-home are increasingly store-prepared.","title":"Trends in energy intake among US children by eating location and food source, 1977–2006"},{"docid":"MED-2180","text":"Objectives To compare the energy and macronutrient content of main meals created by television chefs with ready meals sold by supermarkets, and to compare both with nutritional guidelines published by the World Health Organization and UK Food Standards Agency. Design Cross sectional study. Setting Three supermarkets with the largest share of the grocery market in the United Kingdom, 2010. Samples 100 main meal recipes from five bestselling cookery books by UK television chefs and 100 own brand ready meals from the three leading UK supermarkets. Main outcome measures Number of meals for which the nutritional content complied with WHO recommendations, and the proportion of nutrients classified as red, amber, or green using the UK FSA’s “traffic light” system for labelling food. Results No recipe or ready meal fully complied with the WHO recommendations. The ready meals were more likely to comply with the recommended proportions of energy derived from carbohydrate (18% v 6%, P=0.01) and sugars (83% v 81%, P=0.05) and fibre density (56% v 14% P<0.01). The recipes were more likely to comply with the recommended sodium density (36% v 4%, P<0.01), although salt used for seasoning was not assessed. The distributions of traffic light colours under the FSA’s food labelling recommendations differed: the modal traffic light was red for the recipes (47%) and green for ready meals (42%). Overall, the recipes contained significantly more energy (2530 kJ v 2067 kJ), protein (37.5 g v 27.9 g), fat (27.1 g v 17.2 g), and saturated fat (9.2 g v 6.8 g; P<0.01 for all) and significantly less fibre (3.3 g v 6.5 g, P<0.01) per portion than the ready meals. Conclusions Neither recipes created by television chefs nor ready meals sold by three of the leading UK supermarkets complied with WHO recommendations. Recipes were less healthy than ready meals, containing significantly more energy, protein, fat, and saturated fat, and less fibre per portion than the ready meals.","title":"Christmas 2012: Research: Nutritional content of supermarket ready meals and recipes by television chefs in the United Kingdom: cross sectional study"},{"docid":"MED-2308","text":"Background Few studies have evaluated the linkage between food cost and mortality among older adults. This study considers the hypothesis that greater food expenditure in general, and particularly on more nutritious plant and animal-derived foods, decreases mortality in older adults. Methods This study uses the 1999–2000 Elderly Nutrition and Health Survey in Taiwan and follows the cohort until 2008, collecting 24-hr dietary recall data for 1781 participants (874 men and 907 women) aged 65 y or older. Using monthly mean national food prices and 24-hr recall, this study presents an estimate of daily expenditures for vegetable, fruit, animal-derived, and grain food categories. Participants were linked to the national death registry. Results Of the 1781 original participants, 625 died during the 10-y follow-up period. Among the 4 food categories, the fourth and fifth expenditure quintiles for vegetables and for fruits had the highest survival rates. After adjusting for co-variates, higher (Q4) vegetable and higher fruit (Q4) food expenditures referent to Q1 were significantly predictive of reduced mortality (HR = 0.55, 95% CI: 0.39-0.78 and HR = 0.64, 95% CI: 0.42–0.99, respectively) and the risk decreased by 12% and 10% for every NT$15 (US$0.50) increase in their daily expenditures. Animal-derived and grain food spending was not predictive of mortality. Conclusion Greater and more achievable vegetable and fruit affordability may improve food security and longevity for older adults.","title":"Spending on vegetable and fruit consumption could reduce all-cause mortality among older adults"},{"docid":"MED-1960","text":"Nine catfish fillets, three catfish nuggets, two feed samples, and one pond sediment were analyzed for PCDD, PCDF, and PCB. Farm-raised catfish from Mississippi, Alabama, and Arkansas contained significant levels of 2,3,7,8-substituted PCDD and PCDF. In addition, a large number of non-2,3,7,8-substituted congeners were present in all samples. The catfish fillets and catfish nuggets also contained high concentrations of dioxin-like PCB, as well as a number of non-dioxin-like PCB. The TEQ based on PCDD and PCDF ranged from 9.5 to 43.0 pg/g lipid and the TEQ based on PCB ranged from 0.45 to 4.9 pg/g lipid for all catfish samples. The dioxin-like PCB contributed 4-16% to the total TEQ (PCDD/PCDF/PCB) for the catfish samples. The major source for the PCDD, PCDF, and PCB appears to be from feed and not from pond sediment. Immunoreactive CYP1A protein was elevated 2.5 fold in the pond-raised catfish compared to the aquarium-raised one. The results of this study suggest that the PCDD/PCDF are more important than the PCB in the CYP1A induction.","title":"PCDD, PCDF, and PCB in farm-raised catfish from southeast United States--concentrations, sources, and CYP1A induction."},{"docid":"MED-1540","text":"A number of studies have evaluated the health of vegetarians. Others have studied the health effects of foods that are preferred or avoided by vegetarians. The purpose of this review is to look critically at the evidence on the health effects of vegetarian diets and to seek possible explanations where results appear to conflict. There is convincing evidence that vegetarians have lower rates of coronary heart disease, largely explained by low LDL cholesterol, probable lower rates of hypertension and diabetes mellitus, and lower prevalence of obesity. Overall, their cancer rates appear to be moderately lower than others living in the same communities, and life expectancy appears to be greater. However, results for specific cancers are much less convincing and require more study. There is evidence that risk of colorectal cancer is lower in vegetarians and in those who eat less meat; however, results from British vegetarians presently disagree, and this needs explanation. It is probable that using the label “vegetarian” as a dietary category is too broad and that our understanding will be served well by dividing vegetarians into more descriptive subtypes. Although vegetarian diets are healthful and are associated with lower risk of several chronic diseases, different types of vegetarians may not experience the same effects on health.","title":"Vegetarian diets: what do we know of their effects on common chronic diseases?"},{"docid":"MED-1956","text":"The U.S. Food and Drug Administration (FDA) terminated the use of ball clay from a mine in Mississippi as an additive in animal feed after discovering nanogram per gram concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD). The FDA collected chicken eggs and farm-raised catfish in affected areas and throughout the remaining continental United States to assess levels of 2,3,7,8-TCDD. A new method using quadrupole ion storage tandem-in-time mass spectrometry (QISTMS) measured the 2,3,7,8-TCDD levels in 42 catfish fillet composites, 3 Tilapia fillet composites, 46 chicken egg samples, and 6 chicken feeds. Six catfish composites and 20 egg samples had 2,3,7,8-TCDD concentrations significantly above 1.0 pg/g wet weight of fillet or whole egg. Farm-raised catfish not exposed to feed containing ball clay had a mean 2,3,7,8-TCDD concentration of 0.12 pg/g. The TCDD isomer pattern in ball clay differed from the TCDD isomer pattern in a fly ash sample and from the \"chick edema factor\" TCDD pattern in a sample of reference toxic fat used as a feed ingredient in the 1950s.","title":"Elevated TCDD in chicken eggs and farm-raised catfish fed a diet with ball clay from a Southern United States mine."},{"docid":"MED-2183","text":"Objective Cooking programs are growing in popularity; however an extensive review has not examined overall impact. Therefore, this study reviewed previous research on cooking/home food preparation interventions and diet and health-related outcomes among adults and identified implications for practice and research. Design Literature review and descriptive summative method. Main outcome measures Dietary intake, knowledge/skills, cooking attitudes and self-efficacy/confidence, health outcomes. Analysis Articles evaluating effectiveness of interventions that included cooking/home food preparation as the primary aim (January 1980 through December 2011) were identified via OVID MEDLINE, Agricola and Web of Science databases. Studies grouped according to design and outcomes were reviewed for validity using an established coding system. Results were summarized for several outcome categories. Results Of 28 studies identified, 12 included a control group with six as non-randomized and six as randomized controlled trials. Evaluation was done post-intervention for five studies, pre- and post-intervention for 23 and beyond post-intervention for 15. Qualitative and quantitative measures suggested a positive influence on main outcomes. However, non-rigorous study designs, varying study populations, and use of non-validated assessment tools limited stronger conclusions. Conclusions and Implications Well-designed studies are needed that rigorously evaluate long-term impact on cooking behavior, dietary intake, obesity and other health outcomes.","title":"Impact of cooking and home food preparation interventions among adults: outcomes and implications for future programs"},{"docid":"MED-2184","text":"Objectives. We examined the effects of state-level unemployment rates during the recession of 2008 on patterns of home food preparation and away-from-home (AFH) eating among low-income and minority populations. Methods. We analyzed pooled cross-sectional data on 118 635 adults aged 18 years or older who took part in the American Time Use Study. Multinomial logistic regression models stratified by gender were used to evaluate the associations between state-level unemployment, poverty, race/ethnicity, and time spent cooking, and log binomial regression was used to assess respondents’ AFH consumption patterns. Results. High state-level unemployment was associated with only trivial increases in respondents’ cooking patterns and virtually no change in their AFH eating patterns. Low-income and racial/ethnic minority groups were not disproportionately affected by the recession. Conclusions. Even during a major economic downturn, US adults are resistant to food-related behavior change. More work is needed to understand whether this reluctance to change is attributable to time limits, lack of knowledge or skill related to food preparation, or lack of access to fresh produce and raw ingredients.","title":"Resistant to the Recession: Low-Income Adults’ Maintenance of Cooking and Away-From-Home Eating Behaviors During Times of Economic Turbulence"},{"docid":"MED-2309","text":"BACKGROUND: Similar to the general population in Taiwan, the health of aborigines has steadily improved over the last 30 years, but the gap remains wide, especially in males, despite an infusion of substantial medical resources. The objectives of this study are to quantify the contribution of major causes of death to the gap in life expectancy and to propose initiatives to bridge the health gap between aborigines and the general population. METHODS: This study included residents (slightly over 200000) from 30 'aboriginal townships' in Taiwan. The gap in life expectancy between aborigines and the general population was analysed by decomposing these gaps according to major causes of deaths. This analysis quantifies the contribution of different causes of deaths to the gap in life expectancy between the two populations. RESULTS: The overall mortality of aborigines in these townships was approximately 70% higher than the respective male and female general populations over the past 30 years. Mortality from infectious disease, cirrhosis of the liver, accidents, and suicide are substantially higher than the general population. The gap in life expectancy at birth in males was 8.5 years during 1971-1973, increasing to 13.5 years by 1998-2000, however, the gap in females remained relatively stable (8.0 years and 8.4 years, respectively). Of the 13.5-year difference in life expectancy in males, the differential mortality from diseases of the digestive system (mainly due to cirrhosis of the liver), accidents (from both motor vehicle and non-motor vehicle accidents), and infectious and parasitic disease contributed half (50%) of the gap in life expectancy. In females, the above primarily preventable causes of deaths accounted for 41% of the life expectancy gap. CONCLUSIONS: Based on the findings of this study, we suggest that future focus should be in the area of primary prevention in order to reduce the incidence of infectious and parasitic diseases, liver cirrhosis, and accidents.","title":"Bridging the gap in life expectancy of the aborigines in Taiwan."}],"string":"[\n {\n \"docid\": \"MED-1959\",\n \"text\": \"Since 1991 the US Department of Agriculture (USDA) has conducted annual surveys of pesticide residues in foods under the Agricultural Marketing Service's Pesticide Data Program (PDP). To assess chemical residues in domestically marketed catfish products, 1479 catfish samples were collected during the 2008-2010 PDPs. A subset of 202 samples was analysed for 17 toxic polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs). The average pattern of the individual PCDD/F congener concentrations in the catfish was rather unique in that it had almost no measurable amounts of polychlorinated dibenzofurans (PCDFs), but all PCDDs were present. This pattern was more dominant in the domestically produced catfish products than in the imported products (China/Taiwan). Comparison of the pattern to known sources of PCDD/Fs showed strong similarities to the pattern of PCDD/Fs found in kaolin clays which have often been used as anti-caking agents in animal feeds. To investigate whether catfish feeds may be the source of the PCDD/Fs found in the catfish, archived catfish feed data from a US Food and Drug Administration (USFDA) database were examined. In 61 out of 112 feed samples, the PCDD concentrations were 50 times higher than the PCDF concentrations and resembled the pattern found in the catfish products and in clays mined in the south-eastern United States. Although the source of PCDD/Fs in domestically marketed catfish products cannot be definitively established, mined clay products used in feeds should be considered a likely source and, given the wide concentration range of PCDD/Fs that has been found in clays, a critical control point for PCDD/Fs entrance to the food supply.\",\n \"title\": \"Dioxin congener patterns in commercial catfish from the United States and the indication of mineral clays as the potential source.\"\n },\n {\n \"docid\": \"MED-2179\",\n \"text\": \"OBJECTIVE: To investigate the association between cooking behaviour and long-term survival among elderly Taiwanese. DESIGN: Cohort study. The duration of follow-up was the interval between the date of interview and the date of death or 31 December 2008, when censored for survivors. Information used included demographics, socio-economic status, health behaviours, cooking frequencies, physical function, cognitive function, nutrition knowledge awareness, eating out habits and food and nutrient intakes. These data were linked to death records. Cox proportional-hazards models were used to evaluate cooking frequency on death from 1999 to 2008 with related covariate adjustments. SETTING: Elderly Nutrition and Health Survey in Taiwan, 1999-2000. SUBJECTS: Nationally representative free-living elderly people aged ≥65 years (n 1888). RESULTS: During a 10-year follow-up, 695 participants died. Those who cooked most frequently were younger, women, unmarried, less educated, non-drinkers of alcohol, non-smokers, without chewing difficulty, had spouse as dinner companion, normal cognition, who walked or shopped more than twice weekly, who ate less meat and more vegetables. Highly frequent cooking (>5 times/week, compared with never) predicted survival (hazard ratio (HR) = 0·47; 95 % CI, 0·36, 0·61); with adjustment for physical function, cognitive function, nutrition knowledge awareness and other covariates, HR was 0·59 (95 % CI, 0·41, 0·86). Women benefited more from cooking more frequently than did men, with decreased HR, 51 % v. 24 %, when most was compared with least. A 2-year delay in the assessment of survivorship led to similar findings. CONCLUSIONS: Cooking behaviour favourably predicts survivorship. Highly frequent cooking may favour women more than men.\",\n \"title\": \"Cooking frequency may enhance survival in Taiwanese elderly.\"\n },\n {\n \"docid\": \"MED-2311\",\n \"text\": \"BACKGROUND: The association between fruit and vegetable (FV) consumption and overall mortality has seldom been investigated in large cohort studies. Findings from the few available studies are inconsistent. OBJECTIVE: The objective was to examine the dose-response relation between FV consumption and mortality, in terms of both time and rate, in a large prospective cohort of Swedish men and women. DESIGN: FV consumption was assessed through a self-administrated questionnaire in a population-based cohort of 71,706 participants (38,221 men and 33,485 women) aged 45-83 y. We performed a dose-response analysis to evaluate 10th survival percentile differences (PDs) by using Laplace regression and estimated HRs by using Cox regression. RESULTS: During 13 y of follow-up, 11,439 deaths (6803 men and 4636 women) occurred in the cohort. In comparison with 5 servings FV/d, a lower consumption was progressively associated with shorter survival and higher mortality rates. Those who never consumed FV lived 3 y shorter (PD: -37 mo; 95% CI: -58, -16 mo) and had a 53% higher mortality rate (HR: 1.53; 95% CI: 1.19, 1.99) than did those who consumed 5 servings FV/d. Consideration of fruit and vegetables separately showed that those who never consumed fruit lived 19 mo shorter (PD: -19 mo; 95% CI: -29, -10 mo) than did those who ate 1 fruit/d. Participants who consumed 3 vegetables/d lived 32 mo longer than did those who never consumed vegetables (PD: 32 mo; 96% CI: 13, 51 mo). CONCLUSION: FV consumption <5 servings/d is associated with progressively shorter survival and higher mortality rates. The Swedish Mammography Cohort and the Cohort of Swedish Men were registered at clinicaltrials.gov as NCT01127698 and NCT01127711, respectively.\",\n \"title\": \"Fruit and vegetable consumption and all-cause mortality: a dose-response analysis.\"\n },\n {\n \"docid\": \"MED-1958\",\n \"text\": \"Food, especially meat, milk, and fish, is the immediate source of almost all polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and dioxinlike compounds in the general population. To estimate intake of these highly toxic compounds, we performed congener-specific dioxin analyses for the first time on U.S. food for 18 dairy meat, and fish samples from a supermarket in upstate New York. 2,3,7,8 Tetrachlorodibenzo-p-dioxin (TCDD, \\\"dioxin\\\") toxic equivalents (TEqs) on a wet weight basis for the dairy products ranged for 0.04 to 0.7 ppt, meat TEqs ranged from 0.03 to 1.5 ppt, and fish TEqs ranged from 0.02 to 0.13 ppt. Previous human breast milk and infant formula analyses were used with the current preliminary food data to estimate a range of dioxin intake for Americans. Average daily food intake of TEqs for an adult weighing 65 kg was estimated to be between 0.3 and 3.0 pg/kg body weight, for a total of 18-192 pg TEq, using 1986 American consumption rates. Due to the relatively high level of PCDDs and PCDFs commonly found in human breast milk from American women and from women in other industrial countries, a nursing infant may consume an average of 35-53 pg TEq/kg body weight/day in its first year of life. This may be compared with the current U.S. EPA virtually safe dose of 0.006 pg TCDD/kg body weight per day over a 70-year lifetime based on an upper limit cancer risk of 10(-6), or the 10 pg/kg/day used by some European government agencies.\",\n \"title\": \"Congener-specific levels of dioxins and dibenzofurans in U.S. food and estimated daily dioxin toxic equivalent intake.\"\n },\n {\n \"docid\": \"MED-1963\",\n \"text\": \"In 1994, we analyzed 43 foodstuff samples from local supermarkets in southern Mississippi, USA, for PCDD/PCDF. 2,3,7,8-Cl4DD could be quantified in 31 of these samples. On a lipid basis, levels in meat (0.53-1.10 pg I-TEQ/g) and dairy products (0.42-1.10 pg I-TEQ/g) were slightly lower than those reported from other industrialized countries. While levels in dairy samples from the United States and Europe are comparable, there is a difference in the contribution of individual congeners to the I-TEQ: for example, in milk samples from Germany approximately 40% of the I-TEQ is due to the presence of 2,3, 4,7,8-Cl5DF while in the Mississippi samples this congener only contributes 16%. The highest concentrations of PCDD/PCDF in our study were detected in the farm-raised catfish (10.2-27.8 pg I-TEQ/g). A unique finding was that in addition to the 2,3,7,8-substituted PCDD/PCDF the catfish samples contained many non-2,3,7,8-substituted congeners. This is unusual because vertebrate animals selectively eliminate or metabolize the non-2,3,7,8-substituted congeners.\",\n \"title\": \"Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/PCDF) in food samples collected in southern Mississippi, USA.\"\n },\n {\n \"docid\": \"MED-1962\",\n \"text\": \"The concentrations of the 2,3,7,8-Cl substituted dibenzo-p-dioxins/-furans (PCDDs/PCDFs) were determined in the edible tissues of whole chicken fryers and compared with the values found in their abdominal fat. The values are presented both on a whole weight basis and on a lipid adjusted basis for each tissue. While there is a marked difference in the concentration of the 2,3,7,8-dibenzo-p-dioxins in the edible tissues expressed on a whole weight basis, the lipid-adjusted concentrations of the individual dioxins were not statistically different in the various tissues. This validates the use of lipid adjusted concentrations of 2,3,7,8-PCDDs/PCDFs in abdominal fat for the determination of the presence of these compounds in different tissues.\",\n \"title\": \"The concentration and distribution of 2,3,7,8-dibenzo-p-dioxins/-furans in chickens.\"\n },\n {\n \"docid\": \"MED-2182\",\n \"text\": \"Over the past century, a major shift in North American food practices has been taking place. However, the literature on this topic is lacking in several areas. Some available research on food and cooking practices in the current context is presented, with a focus on how these are affecting health and how they might be contributing to health inequalities within the population. First, cooking and cooking skills are examined, along with the ambiguities related to terms associated with cooking in the research literature. Food choice, cooking, and health are described, particularly in relation to economic factors that may lead to health inequalities within the population. The importance of developing an understanding of factors within the wider food system as part of food choice and cooking skills is presented, and gaps in the research literature are examined and areas for future research are presented. Cooking practices are not well studied but are important to an understanding of human nutritional health as it relates to cultural, environmental, and economic factors.\",\n \"title\": \"Food, cooking skills, and health: a literature review.\"\n },\n {\n \"docid\": \"MED-1957\",\n \"text\": \"One combined catfish feed sample from Arkansas, USA, and its eight ingredients were analyzed for PCDDs and PCDFs. One of the ingredients, soybean meal, was highly contaminated by PCDDs, especially the toxic 2,3,7,8-substituted congeners, e.g., 7.3 pg/g dry weight or 370 pg/g lipid for the 2,3,7,8-tetra CDD. The I-TEQ value for the soybean meal was 11.4 pg/g dry weight or 576 pg/g fat. The corresponding values for the combined catfish feed concentrations were approximately 3 times lower. The congener pattern, the congener profile and the ratio sigma PCDDs/sigma PCDFs for the soybean meal were quite unique. We are not aware of any environmental sample or technical product with similar characteristics. As a result, natural formation of the PCDDs found in the soybean meal cannot be ruled out.\",\n \"title\": \"PCDD and PCDF contamination in catfish feed from Arkansas, USA.\"\n },\n {\n \"docid\": \"MED-2310\",\n \"text\": \"OBJECTIVES To examine the relationship between fruit and vegetable intake, physical activity, and all-cause mortality in older women. DESIGN Six Cox proportional hazards models examined independent and additive relationships between physical activity, carotenoids, and all-cause mortality. Additional models tested whether physical activity and carotenoids were conjointly related to mortality. Models were adjusted for age, education, and race and ethnicity. SETTING Baltimore, Maryland. PARTICIPANTS Seven hundred thirteen women aged 70 to 79 participating in the Women’s Health and Aging Studies. MEASUREMENTS Total serum carotenoids, a marker of fruit and vegetable intake, and physical activity were measured at baseline. Physical activity was measured according to kilocalorie expenditure. RESULTS During 5 years of follow-up, 82 (11.5%) participants died. Measured continuously, physical activity improved survival (HR = 0.52, 95% CI = 0.41–0.66, P < .001). The most active women were more likely to survive than the least physically active women (HR = 0.28, 95% CI = 0.13–0.59, P < .001). Continuous measures of carotenoids improved survival (HR = 0.67, 95% CI = 0.51–0.89, P = .01). Women in the highest tertile of total carotenoids were more likely to survive those in the lowest (HR = 0.50, 95% CI = 0.27–0.91, P = .03). When examined in the same model, continuous measures of physical activity (HR = 0.54, 95% CI = 0.42–0.68, P < .001) and carotenoids (HR = 0.76, 95% CI = 0.59–0.98, P = .04) predicted survival during follow-up. CONCLUSION The combination of low total serum carotenoids and low physical activity, both modifiable risk factors, strongly predicted earlier mortality. These findings provide preliminary support that higher fruit and vegetable intake and exercise improve survival.\",\n \"title\": \"Fruit and Vegetable Intake, Physical Activity, and Mortality in Older Community-Dwelling Women\"\n },\n {\n \"docid\": \"MED-1961\",\n \"text\": \"Dioxins and related compounds are undesirable and unintended contaminants in the food supply, and dietary intake is the major route of exposure. Reducing dietary exposure to dioxins among the most vulnerable segments of the population (i.e., pregnant women, infants, and young girls) is an effective strategy for reducing body burdens in future generations. Exposure to dioxins through foods can be minimized by selecting lower-fat versions of meats, poultry, and dairy products. Consuming all foods, including fatty fish, in recommended amounts is congruent with the goal of reducing dioxin intake exposure and maintaining good health.\",\n \"title\": \"Reducing exposure to dioxins and related compounds through foods in the next generation.\"\n },\n {\n \"docid\": \"MED-1541\",\n \"text\": \"We propose the hypothesis that a vegetarian diet reduces the risk of developing diabetes. Findings that have generated this hypothesis are from a population of 25,698 adult White Seventh-day Adventists identified in 1960. During 21 years of follow-up, the risk of diabetes as an underlying cause of death in Adventists was approximately one-half the risk for all US Whites. Within the male Adventist population, vegetarians had a substantially lower risk than non-vegetarians of diabetes as an underlying or contributing cause of death. Within both the male and female Adventist populations, the prevalence of self-reported diabetes also was lower in vegetarians than in non-vegetarians. The associations observed between diabetes and meat consumption were apparently not due to confounding by over- or under-weight, other selected dietary factors, or physical activity. All of the associations between meat consumption and diabetes were stronger in males than in females.\",\n \"title\": \"Does a vegetarian diet reduce the occurrence of diabetes?\"\n },\n {\n \"docid\": \"MED-2181\",\n \"text\": \"Background Little is known about the impact of location of food consumption and preparation upon daily energy intake for children. Objective To examine trends in daily energy intake by children for foods eaten at home or away-from-home, by source of preparation, and for combined categories of eating location and food source. Subjects The analysis uses data from 29,217 children aged 2–18 years from the 1977–1978 Nationwide Food Consumption Survey, 1989–1991 and 1994–1998 Continuing Survey of Food Intake by Individuals, and 2003–2006 National Health and Nutrition Examination Surveys. Methods Nationally representative weighted percentages and means of daily energy intake by eating location were analyzed for trends from 1977 to 2006. Comparisons by food source were examined from 1994 to 2006. Analyses were repeated for 3 age groups: 2–6, 7–12, and 13–18 year olds. Difference testing was conducted using a t test. Results Increased energy intake (+179 kcal/d) by children from 1977–2006 was associated with a major increase in calories eaten away-from-home (+255 kcal/d). The percentage of kcal/d eaten away-from-home increased from 23.4% to 33.9% from 1977–2006. No further increase was observed from 1994–2006, but the sources of calories shifted. The percentage of calories from fast food increased to surpass intake from schools and become the largest contributor to foods prepared away-from-home for all age groups. For foods eaten away-from-home, the percentage of kcal/d from stores increased to become the largest source of calories eaten away-from-home. Fast food eaten at home and store-bought food eaten away-from-home increased significantly. Conclusion Eating location and food source significantly impact daily energy intake for children. Foods prepared away-from-home, including fast food eaten at home and store-prepared food eaten away-from-home, are fueling the increase in total calorie intake. However, further research using alternative data sources is necessary to verify that store-bought foods eaten away-from-home are increasingly store-prepared.\",\n \"title\": \"Trends in energy intake among US children by eating location and food source, 1977–2006\"\n },\n {\n \"docid\": \"MED-2180\",\n \"text\": \"Objectives To compare the energy and macronutrient content of main meals created by television chefs with ready meals sold by supermarkets, and to compare both with nutritional guidelines published by the World Health Organization and UK Food Standards Agency. Design Cross sectional study. Setting Three supermarkets with the largest share of the grocery market in the United Kingdom, 2010. Samples 100 main meal recipes from five bestselling cookery books by UK television chefs and 100 own brand ready meals from the three leading UK supermarkets. Main outcome measures Number of meals for which the nutritional content complied with WHO recommendations, and the proportion of nutrients classified as red, amber, or green using the UK FSA’s “traffic light” system for labelling food. Results No recipe or ready meal fully complied with the WHO recommendations. The ready meals were more likely to comply with the recommended proportions of energy derived from carbohydrate (18% v 6%, P=0.01) and sugars (83% v 81%, P=0.05) and fibre density (56% v 14% P<0.01). The recipes were more likely to comply with the recommended sodium density (36% v 4%, P<0.01), although salt used for seasoning was not assessed. The distributions of traffic light colours under the FSA’s food labelling recommendations differed: the modal traffic light was red for the recipes (47%) and green for ready meals (42%). Overall, the recipes contained significantly more energy (2530 kJ v 2067 kJ), protein (37.5 g v 27.9 g), fat (27.1 g v 17.2 g), and saturated fat (9.2 g v 6.8 g; P<0.01 for all) and significantly less fibre (3.3 g v 6.5 g, P<0.01) per portion than the ready meals. Conclusions Neither recipes created by television chefs nor ready meals sold by three of the leading UK supermarkets complied with WHO recommendations. Recipes were less healthy than ready meals, containing significantly more energy, protein, fat, and saturated fat, and less fibre per portion than the ready meals.\",\n \"title\": \"Christmas 2012: Research: Nutritional content of supermarket ready meals and recipes by television chefs in the United Kingdom: cross sectional study\"\n },\n {\n \"docid\": \"MED-2308\",\n \"text\": \"Background Few studies have evaluated the linkage between food cost and mortality among older adults. This study considers the hypothesis that greater food expenditure in general, and particularly on more nutritious plant and animal-derived foods, decreases mortality in older adults. Methods This study uses the 1999–2000 Elderly Nutrition and Health Survey in Taiwan and follows the cohort until 2008, collecting 24-hr dietary recall data for 1781 participants (874 men and 907 women) aged 65 y or older. Using monthly mean national food prices and 24-hr recall, this study presents an estimate of daily expenditures for vegetable, fruit, animal-derived, and grain food categories. Participants were linked to the national death registry. Results Of the 1781 original participants, 625 died during the 10-y follow-up period. Among the 4 food categories, the fourth and fifth expenditure quintiles for vegetables and for fruits had the highest survival rates. After adjusting for co-variates, higher (Q4) vegetable and higher fruit (Q4) food expenditures referent to Q1 were significantly predictive of reduced mortality (HR = 0.55, 95% CI: 0.39-0.78 and HR = 0.64, 95% CI: 0.42–0.99, respectively) and the risk decreased by 12% and 10% for every NT$15 (US$0.50) increase in their daily expenditures. Animal-derived and grain food spending was not predictive of mortality. Conclusion Greater and more achievable vegetable and fruit affordability may improve food security and longevity for older adults.\",\n \"title\": \"Spending on vegetable and fruit consumption could reduce all-cause mortality among older adults\"\n },\n {\n \"docid\": \"MED-1960\",\n \"text\": \"Nine catfish fillets, three catfish nuggets, two feed samples, and one pond sediment were analyzed for PCDD, PCDF, and PCB. Farm-raised catfish from Mississippi, Alabama, and Arkansas contained significant levels of 2,3,7,8-substituted PCDD and PCDF. In addition, a large number of non-2,3,7,8-substituted congeners were present in all samples. The catfish fillets and catfish nuggets also contained high concentrations of dioxin-like PCB, as well as a number of non-dioxin-like PCB. The TEQ based on PCDD and PCDF ranged from 9.5 to 43.0 pg/g lipid and the TEQ based on PCB ranged from 0.45 to 4.9 pg/g lipid for all catfish samples. The dioxin-like PCB contributed 4-16% to the total TEQ (PCDD/PCDF/PCB) for the catfish samples. The major source for the PCDD, PCDF, and PCB appears to be from feed and not from pond sediment. Immunoreactive CYP1A protein was elevated 2.5 fold in the pond-raised catfish compared to the aquarium-raised one. The results of this study suggest that the PCDD/PCDF are more important than the PCB in the CYP1A induction.\",\n \"title\": \"PCDD, PCDF, and PCB in farm-raised catfish from southeast United States--concentrations, sources, and CYP1A induction.\"\n },\n {\n \"docid\": \"MED-1540\",\n \"text\": \"A number of studies have evaluated the health of vegetarians. Others have studied the health effects of foods that are preferred or avoided by vegetarians. The purpose of this review is to look critically at the evidence on the health effects of vegetarian diets and to seek possible explanations where results appear to conflict. There is convincing evidence that vegetarians have lower rates of coronary heart disease, largely explained by low LDL cholesterol, probable lower rates of hypertension and diabetes mellitus, and lower prevalence of obesity. Overall, their cancer rates appear to be moderately lower than others living in the same communities, and life expectancy appears to be greater. However, results for specific cancers are much less convincing and require more study. There is evidence that risk of colorectal cancer is lower in vegetarians and in those who eat less meat; however, results from British vegetarians presently disagree, and this needs explanation. It is probable that using the label “vegetarian” as a dietary category is too broad and that our understanding will be served well by dividing vegetarians into more descriptive subtypes. Although vegetarian diets are healthful and are associated with lower risk of several chronic diseases, different types of vegetarians may not experience the same effects on health.\",\n \"title\": \"Vegetarian diets: what do we know of their effects on common chronic diseases?\"\n },\n {\n \"docid\": \"MED-1956\",\n \"text\": \"The U.S. Food and Drug Administration (FDA) terminated the use of ball clay from a mine in Mississippi as an additive in animal feed after discovering nanogram per gram concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD). The FDA collected chicken eggs and farm-raised catfish in affected areas and throughout the remaining continental United States to assess levels of 2,3,7,8-TCDD. A new method using quadrupole ion storage tandem-in-time mass spectrometry (QISTMS) measured the 2,3,7,8-TCDD levels in 42 catfish fillet composites, 3 Tilapia fillet composites, 46 chicken egg samples, and 6 chicken feeds. Six catfish composites and 20 egg samples had 2,3,7,8-TCDD concentrations significantly above 1.0 pg/g wet weight of fillet or whole egg. Farm-raised catfish not exposed to feed containing ball clay had a mean 2,3,7,8-TCDD concentration of 0.12 pg/g. The TCDD isomer pattern in ball clay differed from the TCDD isomer pattern in a fly ash sample and from the \\\"chick edema factor\\\" TCDD pattern in a sample of reference toxic fat used as a feed ingredient in the 1950s.\",\n \"title\": \"Elevated TCDD in chicken eggs and farm-raised catfish fed a diet with ball clay from a Southern United States mine.\"\n },\n {\n \"docid\": \"MED-2183\",\n \"text\": \"Objective Cooking programs are growing in popularity; however an extensive review has not examined overall impact. Therefore, this study reviewed previous research on cooking/home food preparation interventions and diet and health-related outcomes among adults and identified implications for practice and research. Design Literature review and descriptive summative method. Main outcome measures Dietary intake, knowledge/skills, cooking attitudes and self-efficacy/confidence, health outcomes. Analysis Articles evaluating effectiveness of interventions that included cooking/home food preparation as the primary aim (January 1980 through December 2011) were identified via OVID MEDLINE, Agricola and Web of Science databases. Studies grouped according to design and outcomes were reviewed for validity using an established coding system. Results were summarized for several outcome categories. Results Of 28 studies identified, 12 included a control group with six as non-randomized and six as randomized controlled trials. Evaluation was done post-intervention for five studies, pre- and post-intervention for 23 and beyond post-intervention for 15. Qualitative and quantitative measures suggested a positive influence on main outcomes. However, non-rigorous study designs, varying study populations, and use of non-validated assessment tools limited stronger conclusions. Conclusions and Implications Well-designed studies are needed that rigorously evaluate long-term impact on cooking behavior, dietary intake, obesity and other health outcomes.\",\n \"title\": \"Impact of cooking and home food preparation interventions among adults: outcomes and implications for future programs\"\n },\n {\n \"docid\": \"MED-2184\",\n \"text\": \"Objectives. We examined the effects of state-level unemployment rates during the recession of 2008 on patterns of home food preparation and away-from-home (AFH) eating among low-income and minority populations. Methods. We analyzed pooled cross-sectional data on 118 635 adults aged 18 years or older who took part in the American Time Use Study. Multinomial logistic regression models stratified by gender were used to evaluate the associations between state-level unemployment, poverty, race/ethnicity, and time spent cooking, and log binomial regression was used to assess respondents’ AFH consumption patterns. Results. High state-level unemployment was associated with only trivial increases in respondents’ cooking patterns and virtually no change in their AFH eating patterns. Low-income and racial/ethnic minority groups were not disproportionately affected by the recession. Conclusions. Even during a major economic downturn, US adults are resistant to food-related behavior change. More work is needed to understand whether this reluctance to change is attributable to time limits, lack of knowledge or skill related to food preparation, or lack of access to fresh produce and raw ingredients.\",\n \"title\": \"Resistant to the Recession: Low-Income Adults’ Maintenance of Cooking and Away-From-Home Eating Behaviors During Times of Economic Turbulence\"\n },\n {\n \"docid\": \"MED-2309\",\n \"text\": \"BACKGROUND: Similar to the general population in Taiwan, the health of aborigines has steadily improved over the last 30 years, but the gap remains wide, especially in males, despite an infusion of substantial medical resources. The objectives of this study are to quantify the contribution of major causes of death to the gap in life expectancy and to propose initiatives to bridge the health gap between aborigines and the general population. METHODS: This study included residents (slightly over 200000) from 30 'aboriginal townships' in Taiwan. The gap in life expectancy between aborigines and the general population was analysed by decomposing these gaps according to major causes of deaths. This analysis quantifies the contribution of different causes of deaths to the gap in life expectancy between the two populations. RESULTS: The overall mortality of aborigines in these townships was approximately 70% higher than the respective male and female general populations over the past 30 years. Mortality from infectious disease, cirrhosis of the liver, accidents, and suicide are substantially higher than the general population. The gap in life expectancy at birth in males was 8.5 years during 1971-1973, increasing to 13.5 years by 1998-2000, however, the gap in females remained relatively stable (8.0 years and 8.4 years, respectively). Of the 13.5-year difference in life expectancy in males, the differential mortality from diseases of the digestive system (mainly due to cirrhosis of the liver), accidents (from both motor vehicle and non-motor vehicle accidents), and infectious and parasitic disease contributed half (50%) of the gap in life expectancy. In females, the above primarily preventable causes of deaths accounted for 41% of the life expectancy gap. CONCLUSIONS: Based on the findings of this study, we suggest that future focus should be in the area of primary prevention in order to reduce the incidence of infectious and parasitic diseases, liver cirrhosis, and accidents.\",\n \"title\": \"Bridging the gap in life expectancy of the aborigines in Taiwan.\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"MED-3378","text":"BACKGROUND AND OBJECTIVE: In 1981, a Petrol-Lead Phase-Out Program (PLPOP) was launched in Taiwan for the abatement of environmental lead emissions. The present study was intended to examine whether the high Petrol-Lead Emission Areas (PLEA) would result in an increase in the incidence rate of brain cancer based on a national data bank. METHODS: The national brain cancer incidence data was obtained from the Taiwan National Cancer Registry. Age standardized incidence rates were calculated based on the 2000 WHO world standard population, and gasoline consumption data was obtained from the Bureau of Energy. The differences in the trend tests for age-standardized incidence rates of brain cancer between high, median, low, and small PLEA were analyzed. RESULTS: A significant increase was found from small to high PLEA in age-standardized incidence rates of brain cancer. By taking six possible confounders into account, the age-standardized incidence rates for brain cancer were highly correlated with the median and high PLEA by reference to the small PLEA. CONCLUSION: After being adjusted for a number of relevant confounders, it could be concluded that high PLEA might result in an increase in the incidence rate of brain cancer resulting from high lead exposures. Copyright © 2011 Elsevier Ltd. All rights reserved.","title":"Brain cancer associated with environmental lead exposure: evidence from implementation of a National Petrol-Lead Phase-Out Program (PLPOP) in Taiwa..."},{"docid":"MED-2461","text":"This study aimed to evaluate the association of diet with respiratory symptoms and asthma in schoolchildren in Taipei, Taiwan. An in-class interview survey elicited experiences of asthma and respiratory symptoms and consumption frequencies of the major food categories in 2290 fifth graders. Respiratory symptoms surveyed included persistent cough, chest tightness, wheezing with cold, wheezing without cold, dyspnea-associated wheezing, and exercise-induced cough or wheezing. Results showed that the consumption of sweetened beverages had the strongest association with respiratory symptoms and was positively associated with six of the seven respiratory symptoms (all p < 0.05). The adjusted odds ratios (aOR) ranged from 1.05 (95% confidence interval (CI = 1.01-1.09) for exercise-induced cough to 1.09 (95% CI = 1.03-1.16) for wheezing without cold. Egg consumption was associated with 5 of the 7 respiratory symptoms. Consumptions of seafood, soy products, and fruits were each negatively associated with one of the seven respiratory symptoms (all p < 0.05). Consumption of seafood was negatively associated with physician-diagnosed asthma and consumptions of sweetened beverages and eggs were positively associated with suspected asthma (p < 0.05). In conclusion, the study suggests that diet is associated with the respiratory symptoms in schoolchildren in Taipei. Consumptions of sweetened beverages and eggs are associated with increased risk of respiratory symptoms and asthma whereas consumptions of soy products and fruits are associated with reduced risk of respiratory symptoms.","title":"The association of diet with respiratory symptoms and asthma in schoolchildren in Taipei, Taiwan."},{"docid":"MED-118","text":"The aims of this study were to determine the concentrations of 4-nonylphenol (NP) and 4-octylphenol (OP) in 59 human milk samples and to examine related factors including mothers' demographics and dietary habits. Women who consumed over the median amount of cooking oil had significantly higher OP concentrations (0.98 ng/g) than those who consumed less (0.39 ng/g) (P < 0.05). OP concentration was significantly associated with the consumption of cooking oil (beta = 0.62, P < 0.01) and fish oil capsules (beta = 0.39, P < 0.01) after adjustment for age and body mass index (BMI). NP concentration was also significantly associated with the consumption of fish oil capsules (beta = 0.38, P < 0.01) and processed fish products (beta = 0.59, P < 0.01). The food pattern of cooking oil and processed meat products from factor analysis was strongly associated with OP concentration in human milk (P < 0.05). These determinations should aid in suggesting foods for consumption by nursing mothers in order to protect their infants from NP/OP exposure. 2010 Elsevier Ltd. All rights reserved.","title":"Alkylphenols in human milk and their relations to dietary habits in central Taiwan."},{"docid":"MED-2651","text":"The aims of this study were to determine the concentrations of 4-nonylphenol (NP) and 4-octylphenol (OP) in 59 human milk samples and to examine related factors including mothers' demographics and dietary habits. Women who consumed over the median amount of cooking oil had significantly higher OP concentrations (0.98 ng/g) than those who consumed less (0.39 ng/g) (P < 0.05). OP concentration was significantly associated with the consumption of cooking oil (beta = 0.62, P < 0.01) and fish oil capsules (beta = 0.39, P < 0.01) after adjustment for age and body mass index (BMI). NP concentration was also significantly associated with the consumption of fish oil capsules (beta = 0.38, P < 0.01) and processed fish products (beta = 0.59, P < 0.01). The food pattern of cooking oil and processed meat products from factor analysis was strongly associated with OP concentration in human milk (P < 0.05). These determinations should aid in suggesting foods for consumption by nursing mothers in order to protect their infants from NP/OP exposure. 2010 Elsevier Ltd. All rights reserved.","title":"Alkylphenols in human milk and their relations to dietary habits in central Taiwan."},{"docid":"MED-1613","text":"The present study was designed to examine the effects of habitual consumption of Taiwanese vegetarian diets on hormonal secretion, and on lipid and glycaemic control. Of the ninety-eight healthy female adults recruited from Hualien, Taiwan (aged 31-45 years), forty-nine were Buddhist lactovegetarians and forty-nine were omnivores. Dietary intakes were measured, and blood levels of nutrients and hormones were analysed. Vegetarians consumed less energy, fat and protein, but more fibre than the omnivores. Compared with the omnivores, the vegetarians had, on average, lower BMI and smaller waist circumference. Except for slightly lower levels of thyroxine (T4) in vegetarians, vegetarians and omnivores both showed similar levels of triiodothyronine (T3), free T4, thyroid-stimulating hormone, T3:T4 ratio and cortisol. Compared with the omnivores, the vegetarians had significantly lower levels of fasting insulin (median: 35.3 v. 50.6 pmol/l) and plasma glucose (mean: 4.7 (se 0.05) v. 4.9 (se 0.05) mmol/l). Insulin resistance, as calculated by the homeostasis model assessment method, was significantly lower in the vegetarians than in the omnivores (median: 1.10 v. 1.56), while beta-cell function was not different between the two groups. BMI and diet were both independent predictors for insulin resistance, and contributed 18 and 15 % of the variation in insulin resistance, respectively. In conclusion, Taiwanese vegetarians had lower glucose and insulin levels and higher insulin sensitivity than did the omnivores. Diet and lower BMI were partially responsible for the high insulin sensitivity observed in young Taiwanese vegetarians.","title":"Taiwanese vegetarians have higher insulin sensitivity than omnivores."},{"docid":"MED-3947","text":"Hibiscus sabdariffa Linne (Malvaceae), an attractive plant believed to be native to Africa, is cultivated in the Sudan and Eastern Taiwan. Anthocyanins exist widely in many vegetables and fruits. Some reports demonstrated that anthocyanins extracted from H. sabdariffa L., Hibiscus anthocyanins (HAs) (which are a group of natural pigments existing in the dried calyx of H. sabdariffa L.) exhibited antioxidant activity and liver protection. Therefore, in this study, we explored the effect of HAs on human cancer cells. The result showed that HAs could cause cancer cell apoptosis, especially in HL-60 cells. Using flow cytometry, we found that HAs treatment (0-4 mg/ml) markedly induced apoptosis in HL-60 cells in a dose- and time-dependent manner. The result also revealed increased phosphorylation in p38 and c-Jun, cytochrome c release, and expression of tBid, Fas, and FasL in the HAs-treated HL-60 cells. We further used SB203580 (p38 inhibitor), PD98059 (MEK inhibitor), SP600125 (JNK inhibitor), and wortmannin (phosphatidylinositol 3-kinase; PI-3K inhibitor) to evaluate their effect on the HAs-induced HL-60 death. The data showed that only SB203580 had strong potential in inhibiting HL-60 cell apoptosis and related protein expression and phosphorylation. Therefore, we suggested that HAs mediated HL-60 apoptosis via the p38-FasL and Bid pathway. According to these results, HAs could be developed as chemopreventive agents. However, further investigations into the specificity and mechanism(s) of HAs are needed.","title":"Hibiscus anthocyanins rich extract-induced apoptotic cell death in human promyelocytic leukemia cells."},{"docid":"MED-3681","text":"OBJECTIVE: To determine the effects of the probiotic lactic acid bacterium, Lactobacillus rhamnosus HN001, on natural cellular immunity when delivered orally in normal low-fat milk (LFM) or lactose-hydrolyzed low-fat milk (LFM-LH). DESIGN: A three stage, pre-post intervention trial, spanning nine weeks. SETTING: Taipei Medical College Hospital, Taipei, Taiwan. SUBJECTS: Fifty-two healthy middle-aged and elderly volunteers (17 males, 35 females; median age 63.5, range 44-80). INTERVENTIONS: Stage 1 (run-in diet): 25 g/200 mL reconstituted LFM powder, twice daily for 3 weeks. Stage 2 (probiotic intervention): LFM or LFM-LH, supplemented with 10(9) CFUs/g L. rhamnosus HN001 in each case, for 3 weeks. Stage 3 (wash-out): LFM for 3 weeks. MEASURES OF OUTCOME: In vitro phagocytic capacity of peripheral blood polymorphonuclear (PMN) leukocytes; in vitro tumoricidal activity of natural killer (NK) leukocytes. RESULTS: Immunological responses were unaffected by the run-in diet of LFM alone. In contrast, the relative proportion of PMN cells showing phagocytic activity increased by 19% and 15%, respectively, following consumption of HN001 in either LFM or LFM-LH; the relative level of NK cell tumor killing activity increased by 71% and 147%. In most cases these levels declined following cessation, but remained above baseline. CONCLUSIONS: Dietary consumption of L. rhamnosus HN001, in a base of low-fat milk or lactose-hydrolyzed low-fat milk, appears to enhance systemic cellular immune responses and may be useful as a dietary supplement to boost natural immunity.","title":"Systemic immunity-enhancing effects in healthy subjects following dietary consumption of the lactic acid bacterium Lactobacillus rhamnosus HN001."},{"docid":"MED-4832","text":"Cardiovascular disease (CVD) is the most important adult health problem in the world. Epidemiological studies and laboratory experiments have shown that fruit and vegetable consumption has protective effects against CVD. The purpose of the study was to investigate the effects of consumption of two kiwifruit per day on the lipid profile, antioxidants and markers of lipid peroxidation in hyperlipidemic adult men and women in Taiwan. Forty-three subjects who had hyperlipidemia, including 13 males and 30 females, participated in this study. They were asked to consume two kiwifruit per day for 8 weeks. Anthropometric measurements were made. Before the intervention and at 4 and 8 weeks of the intervention, fasting blood samples were analyzed for total cholesterol, triacylglycerol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein cholesterol (HDL-C). Additionally vitamin E and vitamin C, the malondialdehyde + 4-hydroxy-2(E)-nonenal concentration, and the lag time of LDL oxidation were determined. No significant differences from baseline to 8 weeks of the intervention were detected for triacylglycerol, total cholesterol, or LDL cholesterol. However, after 8 weeks of consumption of kiwifruit, the HDL-C concentration was significantly increased and the LDL cholesterol/HDL-C ratio and total cholesterol/HDL-C ratio were significantly decreased. Vitamin C and vitamin E also increased significantly. In addition, the lag time of LDL oxidation and malondialdehyde + 4-hydroxy-2(E)-nonenal had significantly changed at 4 and 8 weeks during the kiwifruit intervention. Regular consumption of kiwifruit might exert beneficial effects on the antioxidative status and the risk factors for CVD in hyperlipidemic subjects.","title":"Effects of kiwifruit consumption on serum lipid profiles and antioxidative status in hyperlipidemic subjects."},{"docid":"MED-4093","text":"OBJECTIVE: The association between hyperuricemia and cardiovascular events has been documented in high-risk groups, but is still undetermined in general populations, especially Chinese. This study assessed the temporal association between serum uric acid level, hyperuricemia, and cardiovascular mortality. METHODS: A prospective cohort study of 41,879 men and 48,514 women ages > or = 35 years was conducted using data from the MJ Health Screening Centers in Taiwan. Mortality from all causes, total cardiovascular disease (CVD), ischemic stroke, congestive heart failure, hypertensive disease, and coronary heart disease were compared according to increasing serum uric acid levels. RESULTS: A total of 1,151 (21.2%) events of 5,427 total deaths were ascribed to CVD (mean followup 8.2 years). Hazard ratios (HRs) for hyperuricemia (serum uric acid level >7 mg/dl) were estimated with Cox regression model after adjusting for age, sex, body mass index, cholesterol, triglycerides, diabetes, hypertension, heavy cigarette smoking, and frequent alcohol consumption. In all patients, HRs were 1.16 (P < 0.001) for all-cause mortality, 1.39 (P < 0.001) for total CVD, and 1.35 (P = 0.02) for ischemic stroke. In subgroup analysis, the HRs for cardiovascular risk remained significant in patients with hypertension (1.44, P < 0.001) and in patients with diabetes (1.64, P < 0.001). In addition, in a low metabolic risk subgroup, the HRs for all-cause mortality and total cardiovascular morbidity were 1.24 (P = 0.02) and 1.48 (P = 0.16), respectively. CONCLUSION: Hyperuricemia was an independent risk factor of mortality from all causes, total CVD, and ischemic stroke in the Taiwanese general population, in high-risk groups, and potentially in low-risk groups.","title":"Serum uric acid level as an independent risk factor for all-cause, cardiovascular, and ischemic stroke mortality: a Chinese cohort study."},{"docid":"MED-3435","text":"INTRODUCTION: Previous cross-sectional studies have suggested that erectile dysfunction (ED) represents an independent risk factor for future cardiovascular events. However, very few studies have attempted to examine the association between ED and subsequent stroke. AIM: The aim of this study is to estimate the risk of stroke during a 5-year follow-up period after the first ambulatory care visit for the treatment of ED using nationwide, population-based data and a retrospective case-control cohort design in Taiwan. METHODS: This study used data sourced from the \"Longitudinal Health Insurance Database.\" The study cohort comprised 1,501 patients who received a principal diagnosis of ED between 1997 and 2001 and 7,505 randomly selected subjects as the comparison cohort. Each patient (N = 9,006) was then individually tracked for 5 years from their index ambulatory care visit to identify those who had diagnosed episodes of stroke. MAIN OUTCOME MEASURE: Stratified Cox proportional hazard regressions were performed as a means of comparing the 5-year stroke-free survival rate for the two cohorts. RESULTS: Of the sampled patients, 918 (10.2%) developed stroke within the 5-year follow-up period, that is, 188 individuals (12.5% of the patients with ED) from the study cohort and 730 individuals (9.7% of patients in the comparison cohort) from the comparison cohort. The log-rank test indicated that patients with ED had significantly lower 5-year stroke-free survival rates than those in the comparison cohort (P < 0.001). After adjusting for the patient's monthly income, geographical location, hypertension, diabetes, coronary heart disease, peripheral vascular disease, atrial fibrillation, and hyperlipidemia, patients with ED were more likely to have a stroke during the 5-year follow-up period than patients in the comparison cohort (hazard ratio = 1.29, 95% confidence interval = 1.08 - 1.54, P < 0.01). CONCLUSIONS: These results suggest that ED is a surrogate marker for future stroke in men. © 2010 International Society for Sexual Medicine.","title":"Increased risk of stroke among men with erectile dysfunction: a nationwide population-based study."},{"docid":"MED-931","text":"This study evaluated the toxicological sensitivity of non-feeding larval stages of a key Antarctic species (Antarctic krill, Euphausia superba) to p,p'-dichlorodiphenyl dichloroethylene (p,p'-DDE) exposure. The aqueous uptake clearance rate of 84 mL g(-1) preserved weight (p.w.) h(-1) determined for p,p'-DDE in Antarctic krill larvae is comparable to previous findings for small cold water crustaceans and five times slower than the rates reported for an amphipod inhabiting warmer waters. Natural variations in larval physiology appear to influence contaminant uptake and larval krill behavioural responses, strongly highlighting the importance of time of measurement for ecotoxicological testing. Sublethal narcosis (immobility) was observed in larval Antarctic krill from p,p'-DDE body residues of 0.2 mmol/kg p.w., which is in agreement with findings for adult krill and temperate aquatic species. The finding of comparable body residue-based toxicity of p,p'-DDE between polar and temperate species supports the tissue residue approach for environmental risk assessment of polar ecosystems. Copyright © 2011 Elsevier Ltd. All rights reserved.","title":"Aqueous uptake and sublethal toxicity of p,p'-DDE in non-feeding larval stages of Antarctic krill (Euphausia superba)."},{"docid":"MED-3371","text":"Background: The overconsumption of energy-dense foods leads to excessive energy intakes. The substitution of low-energy-dense vegetables for foods higher in energy density can help decrease energy intakes but may be difficult to implement if individuals dislike the taste of vegetables. Objective: We investigated whether incorporating puréed vegetables to decrease the energy density of entrées at multiple meals reduced daily energy intakes and increased daily vegetable intakes. Design: In this crossover study, 20 men and 21 women ate ad libitum breakfast, lunch, and dinner in the laboratory once a week for 3 wk. Across conditions, entrées at meals varied in energy density from standard versions (100% condition) to reduced versions (85% and 75% conditions) by the covert incorporation of 3 or 4.5 times the amount of puréed vegetables. Entrées were accompanied by unmanipulated side dishes. Participants rated their hunger and fullness before and after meals. Results: Subjects consumed a consistent weight of foods across conditions of energy density; thus, the daily energy intake significantly decreased by 202 ± 60 kcal in the 85% condition (P < 0.001) and by 357 ± 47 kcal in the 75% condition (P < 0.0001). Daily vegetable consumption significantly increased from 270 ± 17 g of vegetables in the 100% condition to 487 ± 25 g of vegetables in the 75% condition (P < 0.0001). Despite the decreased energy intake, ratings of hunger and fullness did not significantly differ across conditions. Entrées were rated as similar in palatability across conditions. Conclusions: Large amounts of puréed vegetables can be incorporated into various foods to decrease the energy density. This strategy can lead to substantial reductions in energy intakes and increases in vegetable intakes. This trial was registered at clinicaltrials.gov as NCT01165086.","title":"Hidden vegetables: an effective strategy to reduce energy intake and increase vegetable intake in adults"},{"docid":"MED-1218","text":"There has been a recent increase in community-associated infections linked to methicillin-resistant Staphylococcus aureus (MRSA) and Clostridium difficile. It is established that both pathogens can be recovered from retail pork, although it is unclear to what degree contamination is acquired at the farm in comparison to that acquired during processing. To address this gap, the following study reports on the carriage of MRSA and C. difficile on pigs from birth through to the end of processing. C. difficile was isolated from 28 (93%) of 30 pigs at 1 day of age, but prevalence declined sharply to 1 of 26 by market age (188 days). MRSA prevalence peaked at 74 days of age, with 19 (68%) of 28 pigs testing positive, but declined to 3 of 26 at 150 days of age, with no pig being detected as positive at market age. At the processing facility, C. difficile was isolated from the holding area, with a single carcass testing positive for the pathogen at preevisceration. MRSA was primarily isolated from nasal swabs with 8 (31%) carcasses testing positive at postbleed, which increased to 14 (54%) positive at postscald tanks. Only one carcass (sampled at postbleed) tested positive for MRSA, with no recovery of the pathogen from environmental samples taken. C. difficile ribotype 078 predominated in the longitudinal portion of the study, accounting for all of the 68 isolates recovered from pigs. Only three C. difficile isolates, which were identified as ribotype 078, were recovered at the slaughterhouse. MRSA spa type 539 (t034) predominated in pigs on the farm and samples taken at the slaughterhouse, accounting for 80% of all isolates recovered. The study demonstrated that both C. difficile and MRSA acquired on the farm can be transferred through to processing, although no evidence for significant cross-contamination between carcasses or the slaughterhouse environment was evident.","title":"Longitudinal study of Clostridium difficile and Methicillin-resistant Staphylococcus aureus associated with pigs from weaning through to the end of..."},{"docid":"MED-2972","text":"BACKGROUND: Elevated levels of lipids, such as total cholesterol (TC), low-density lipoprotein cholesterol (LDL), and triglycerides (TG), are widely recognized as risk factors for cardiovascular disease (CVD). Oxidized LDL (OxLDL) is an emerging risk factor considered relevant in oxidative stress and endothelial dysfunction, which is implicated in the progression of CVD. Consumption of a diet rich in polyphenols may be cardioprotective through its impact on oxidative stress and protecting LDL from oxidation. OBJECTIVES: This study was designed to test the ability of strawberry phenolic compounds to mitigate the postprandial effects of a high-fat meal on OxLDL as well as investigate the effects of phenolic compounds on lipid metabolism. METHODS: Twenty-four hyperlipidemic men and women (14 women, 10 men; mean age 50.9 +/- SD 15 years) were recruited to participate in this randomized, single-blind, placebo-controlled, 12-wk crossover trial. After a 10-day run-in period, subjects consumed either an active strawberry beverage (Str; containing 10 g freeze-dried fruit) or a placebo (Pbo) beverage matched in energy and macronutrient composition for 6 weeks. Twice before randomization and once at the 6-week crossover point, subjects received either Str or Pbo with a high-fat challenge meal (HFM). TC, LDL, high-density lipoprotein cholesterol, TG, and OxLDL were measured at defined intervals for 6 h before and after HFM challenge. Fasting concentrations of blood variables at 0, 6, and 12 weeks were compared to assess chronic intake of Str or Pbo. RESULTS: After the HFM during the run-in period, TG and OxLDL were lower after Str than Pbo (p = 0.005, p = 0.01, and p = 0.0008, respectively). HFM responses after 6 weeks of Str versus Pbo resulted in decreased lipid levels and a sex by treatment interaction for OxLDL (p = < 0.0001, and p = 0.0002). CONCLUSION: The present results support a role for strawberry in mitigating fed-state oxidative stressors that may contribute to atherogenesis.","title":"Strawberry modulates LDL oxidation and postprandial lipemia in response to high-fat meal in overweight hyperlipidemic men and women."},{"docid":"MED-3161","text":"Intense exercise is directly related to muscular damage and oxidative stress due to excessive reactive oxygen species (ROS) in both, plasma and white blood cells. Nevertheless, exercise-derived ROS are essential to regulate cellular adaptation to exercise. Studies on antioxidant supplements have provided controversial results. The purpose of this study was to determine the effect of moderate antioxidant supplementation (lemon verbena extract) in healthy male volunteers that followed a 90-min running eccentric exercise protocol for 21 days. Antioxidant enzymes activities and oxidative stress markers were measured in neutrophils. Besides, inflammatory cytokines and muscular damage were determined in whole blood and serum samples, respectively. Intense running exercise for 21 days induced antioxidant response in neutrophils of trained male through the increase of the antioxidant enzymes catalase, glutathione peroxidase and glutathione reductase. Supplementation with moderate levels of an antioxidant lemon verbena extract did not block this cellular adaptive response and also reduced exercise-induced oxidative damage of proteins and lipids in neutrophils and decreased myeloperoxidase activity. Moreover, lemon verbena supplementation maintained or decreased the level of serum transaminases activity indicating a protection of muscular tissue. Exercise induced a decrease of interleukin-6 and interleukin-1β levels after 21 days measured in basal conditions, which was not inhibited by antioxidant supplementation. Therefore, moderate antioxidant supplementation with lemon verbena extract protects neutrophils against oxidative damage, decreases the signs of muscular damage in chronic running exercise without blocking the cellular adaptation to exercise.","title":"Effect of lemon verbena supplementation on muscular damage markers, proinflammatory cytokines release and neutrophils' oxidative stress in chronic ..."},{"docid":"MED-3981","text":"The aim of this study was to investigate the relationship between child characteristics, parental and environmental factors and the occurrence of acute respiratory illness (ARI) and acute otitis media (AOM) among Finnish children attending day care centres (DCCs). The study was a cross-sectional questionnaire of 594 children aged 1-6 y from 18 DCCs in Helsinki, Finland. Recurrent (> or =4 diseases/y) ARI was present in 44% of the 1-3-y-olds and 23% of the 4-6-y-olds, and recurrent AOM in 15% and 2.5%, respectively. Parent atopic disease (odds ratio (OR) 1.53, p = 0.033), mother's academic education (OR 1.77, p = 0.008) and a medium length of DCC attendance compared to a short period (OR 1.67, p = 0.049) increased, while furry pets (OR 0.44, p = 0.003) and older child age (OR 0.38, p < 0.001) reduced the risk of recurrent ARI. Recurrent ARI (OR 3.96, p = 0.008), mother's academic education (OR 5.02, p = 0.003), and a medium length of DCC attendance compared to a short period (OR 3.34, p = 0.044) increased, while partial breastfeeding > or =6 months (OR 0.20, p = 0.002) and older child age (OR 0.05, p < 0.001) reduced the risk of recurrent AOM. Parental and environmental factors had a significant impact on recurrent ARI and AOM episodes in children attending DCCs. These risk factors should be considered in future studies intending to reduce DCC infections.","title":"Factors associated with acute respiratory illness in day care children."},{"docid":"MED-2469","text":"The intestinal flora is considered to have an impact on the development of the immune system. In the anthroposophic lifestyle, a diet comprising vegetables spontaneously fermented by lactobacilli, and a restrictive use of antibiotics, anti-pyretics and vaccinations, is typical. The aim of this study was to assess the gut flora in infants in relation to certain lifestyle characteristics associated with anthroposophy. Sixty-nine children < 2 years of age with an anthroposophic lifestyle, and 59 infants of a similar age with a traditional lifestyle, were clinically examined and questionnaire replies assessed. Fecal samples were analyzed by bacterial enumeration, bacterial typing through biochemical fingerprinting and by measuring microflora-associated characteristics (MACs). The numbers of colony-forming units (CFU)/g of feces were significantly higher for enterococci and lactic acid bacteria in children who had never been exposed to antibiotics (5.5 x 107 vs. 2.1 x 107; p < 0.001 and 10 x 107 vs. 4.1 x 107; p < 0.01, respectively). Furthermore, the number of enterococci was significantly higher in breastfed and vegetarian infants (p < 0.01). The diversity (Simpson's diversity index) of lactobacilli, as determined by biochemical fingerprinting, was higher in infants born at home than in those born in hospital (p < 0.01). Several MACs were related to specific lifestyle features, and infants with an anthroposophic lifestyle had a higher proportion of acetic acid and a lower proportion of propionic acid in their stool as compared to the control children. In conclusion, lifestyle factors related to the anthroposophic way of life influenced the composition of the gut flora in the infants. These differences may contribute to the lower prevalence of atopic disease previously observed in children in anthroposophic families.","title":"An anthroposophic lifestyle and intestinal microflora in infancy."},{"docid":"MED-870","text":"Ilex paraguariensis dried and minced leaves are made into a brewed tea, prepared in a sui generis manner by large populations in South America, having evolved from a tea drunk by the Guarani ethnic group to a beverage that has a social and almost ritualistic role in some South American modern societies. It is used both as a source of caffeine, in lieu or in parallel with tea and coffee, but also as a therapeutic agent for its alleged pharmacological properties. Although with some exceptions, research on biomedical properties of this herb has had a late start and strongly lags behind the impressive amount of literature on green tea and coffee. However, in the past 15 years, there was a several-fold increase in the literature studying Ilex paraguariensis properties showing effects such as antioxidant properties in chemical models and ex vivo lipoprotein studies, vaso-dilating and lipid reduction properties, antimutagenic effects, controversial association with oropharyngeal cancer, anti-glycation effects and weight reduction properties. Lately, promising results from human intervention studies have surfaced and the literature offers several developments on this area. The aim of this review is to provide a concise summary of the research published in the past three years, with an emphasis on translational studies, inflammation and lipid metabolism. Ilex paraguariensis reduces LDL-cholesterol levels in humans with Ilex paraguariensis dyslipoproteinemia and the effect is synergic with that of statins. Plasma antioxidant capacity as well as expression of antioxidant enzymes is positively modulated by intervention with Ilex paraguariensis in human cohorts. A review on the evidence implicating Ilex paraguariensis heavy consumption with some neoplasias show data that are inconclusive but indicate that contamination with alkylating agents during the drying process of the leaves should be avoided. On the other hand, several new studies confirm the antimutagenic effects of Ilex paraguariensis in different models, from DNA double breaks in cell culture models to mice studies. Novel interesting work has emerged showing significant effect on weight reduction both in mice and in rat models. Some mechanisms involved are inhibition of pancreatic lipase, activation of AMPK and uncoupling of electron transport. Intervention studies in animals have provided strong evidence of anti-inflammatory effects of Ilex paraguariensis, notably protecting cigarette-induced lung inflammation acting on macrophage migration and inactivating matrix-metalloproteinase. Research on the effects of Ilex paraguariensis in health and disease has confirmed its antioxidant, anti-inflammatory, antimutagenic and lipid-lowering activities. Although we are still waiting for the double-blind, randomized prospective clinical trial, the evidence seems to provide support for beneficial effects of mate drinking on chronic diseases with inflammatory component and lipid metabolism disorders. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.","title":"Recent advances on Ilex paraguariensis research: minireview."},{"docid":"MED-1151","text":"Background: Organically produced foods are less likely than conventionally produced foods to contain pesticide residues. Methods: We examined the hypothesis that eating organic food may reduce the risk of soft tissue sarcoma, breast cancer, non-Hodgkin lymphoma and other common cancers in a large prospective study of 623 080 middle-aged UK women. Women reported their consumption of organic food and were followed for cancer incidence over the next 9.3 years. Cox regression models were used to estimate adjusted relative risks for cancer incidence by the reported frequency of consumption of organic foods. Results: At baseline, 30%, 63% and 7% of women reported never, sometimes, or usually/always eating organic food, respectively. Consumption of organic food was not associated with a reduction in the incidence of all cancer (n=53 769 cases in total) (RR for usually/always vs never=1.03, 95% confidence interval (CI): 0.99–1.07), soft tissue sarcoma (RR=1.37, 95% CI: 0.82–2.27), or breast cancer (RR=1.09, 95% CI: 1.02–1.15), but was associated for non-Hodgkin lymphoma (RR=0.79, 95% CI: 0.65–0.96). Conclusions: In this large prospective study there was little or no decrease in the incidence of cancer associated with consumption of organic food, except possibly for non-Hodgkin lymphoma.","title":"Organic food consumption and the incidence of cancer in a large prospective study of women in the United Kingdom"},{"docid":"MED-4846","text":"The effects of a strict uncooked vegan diet on serum lipid and sterol concentrations were studied in patients with rheumatoid arthritis. The subjects were randomized into a vegan diet group (n 16), who consumed a vegan diet for 2-3 months, or into a control group (n 13), who continued their usual omnivorous diets. Serum total and LDL-cholesterol and -phospholipid concentrations were significantly decreased by the vegan diet. The levels of serum cholestanol and lathosterol also decreased, but serum cholestanol:total cholesterol and lathosterol:total cholesterol did not change. The effect of a vegan diet on serum plant sterols was divergent as the concentration of campesterol decreased while that of sitosterol increased. This effect resulted in a significantly greater sitosterol:campesterol value in the vegan diet group than in the control group (1.48 (SD 0.39) v. 0.72 (SD 0.14); P < 0.001). A higher concentration of campesterol compared with sitosterol is normal in omnivorous subjects and can be explained by lower absorption and esterification rates of sitosterol. Our results suggest that a strict uncooked vegan diet changes the relative absorption rates of these sterols and/or their biliary clearance.","title":"Divergent changes in serum sterols during a strict uncooked vegan diet in patients with rheumatoid arthritis."},{"docid":"MED-2122","text":"OBJECTIVE: To clarify the hormonal context of breast cancer etiology we used data from a large, population-based case-control study to investigate the relationship between breast cancer risk and a history of diabetes mellitus, disorders associated with estrogen stimulation (uterine fibroids, endometriosis, gallstones), and disorders associated with androgen stimulation (acne, hirsutism, and polycystic ovaries). METHODS: Breast cancer patients between 50 and 75 years old were identified from state-wide tumor registries in Wisconsin, Massachusetts, and New Hampshire; controls were randomly selected from drivers' license lists (age less than 65) or Medicare enrollment files (age 65-74). Information on reproductive history, medical history, and personal habits was obtained by telephone interview. A total of 5659 cases and 5928 controls were interviewed and provided suitable data. RESULTS: There was no overall association between breast cancer risk and reported history of diabetes mellitus, endometriosis, uterine fibroids, gallstones, or cholecystectomy. However, the disorders with androgenic associations all conferred an increased risk: the overall odds ratio (OR) for a history of acne was 1.4 (95% CI 1.0-1.9), that for hirsutism was 1.2 (95% CI 0.81-1.8), and that for polycystic ovaries 1.6 (95% CI 0.8-3.2). Diabetes mellitus diagnosed before age 35 conferred an odds ratio of 0.52 (95% 0.25-1.1), while diabetes diagnosed at a later age was associated with an increased risk (OR = 1.2, 95% CI 1.0-1.4). CONCLUSIONS: Androgen-related phenomena are likely to be important in the etiology of breast cancer.","title":"Metabolic disorders and breast cancer risk (United States)."},{"docid":"MED-1338","text":"Objective To examine whether high milk consumption is associated with mortality and fractures in women and men. Design Cohort studies. Setting Three counties in central Sweden. Participants Two large Swedish cohorts, one with 61 433 women (39-74 years at baseline 1987-90) and one with 45 339 men (45-79 years at baseline 1997), were administered food frequency questionnaires. The women responded to a second food frequency questionnaire in 1997. Main outcome measure Multivariable survival models were applied to determine the association between milk consumption and time to mortality or fracture. Results During a mean follow-up of 20.1 years, 15 541 women died and 17 252 had a fracture, of whom 4259 had a hip fracture. In the male cohort with a mean follow-up of 11.2 years, 10 112 men died and 5066 had a fracture, with 1166 hip fracture cases. In women the adjusted mortality hazard ratio for three or more glasses of milk a day compared with less than one glass a day was 1.93 (95% confidence interval 1.80 to 2.06). For every glass of milk, the adjusted hazard ratio of all cause mortality was 1.15 (1.13 to 1.17) in women and 1.03 (1.01 to 1.04) in men. For every glass of milk in women no reduction was observed in fracture risk with higher milk consumption for any fracture (1.02, 1.00 to 1.04) or for hip fracture (1.09, 1.05 to 1.13). The corresponding adjusted hazard ratios in men were 1.01 (0.99 to 1.03) and 1.03 (0.99 to 1.07). In subsamples of two additional cohorts, one in males and one in females, a positive association was seen between milk intake and both urine 8-iso-PGF2α (a biomarker of oxidative stress) and serum interleukin 6 (a main inflammatory biomarker). Conclusions High milk intake was associated with higher mortality in one cohort of women and in another cohort of men, and with higher fracture incidence in women. Given the observational study designs with the inherent possibility of residual confounding and reverse causation phenomena, a cautious interpretation of the results is recommended.","title":"Milk intake and risk of mortality and fractures in women and men: cohort studies"},{"docid":"MED-762","text":"The Ethiopian Field Epidemiology and Laboratory Training Program (EFELTP) is a comprehensive two-year competency-based training and service program designed to build sustainable public health expertise and capacity. Established in 2009, the program is a partnership between the Ethiopian Federal Ministry of Health, the Ethiopian Health and Nutrition Research Institute, Addis Ababa University School of Public Health, the Ethiopian Public Health Association and the US Centers of Disease Control and Prevention. Residents of the program spend about 25% of their time undergoing didactic training and the 75% in the field working at program field bases established with the MOH and Regional Health Bureaus investigating disease outbreaks, improving disease surveillance, responding to public health emergencies, using health data to make recommendations and undertaking other field Epidemiology related activities on setting health policy. Residents from the first 2 cohorts of the program have conducted more than 42 outbreaks investigations, 27analyses of surveillance data, evaluations of 11 surveillance systems, had28oral and poster presentation abstracts accepted at 10 scientific conferences and submitted 8 manuscripts of which 2are already published. The EFELTP has provided valuable opportunities to improve epidemiology and laboratory capacity building in Ethiopia. While the program is relatively young, positive and significant impacts are assisting the country better detect and respond to epidemics and address diseases of major public health significance.","title":"The Ethiopian Field Epidemiology and Laboratory Training Program: strengthening public health systems and building human resource capacity."},{"docid":"MED-2115","text":"Dietary PUFA, mainly those of the n-3 family, are known to play essential roles in the maintenance of energy balance and in the reduction of body fat deposition through the upregulation of mitochondrial uncoupling that is the main source of reactive oxygen species. We hypothesized that rat supplementation with raw donkey's milk (DM), characterized by low-fat content and higher n3:n6 ratio, may affect energy balance, lipid metabolism, and prooxidant status as compared to animals treated with cow's milk. In the present study, the effects of drinking raw DM (for 4 weeks) on energy balance, lipid metabolism, antiinflammatory, and antioxidant/detoxifying defences was compared to that produced by rat intake of an iso-energetic amount of raw cow's milk. The hypolipidemic effect produced by DM paralleled with the enhanced mitochondrial activity/proton leakage and with the increased activity or expression of mitochondrial markers namely, carnitine palmitoyl transferase and uncoupling protein 2. The association of decreased energy efficiency with reduced proinflammatory signs (TNF-α and LPS levels) with the significant increase antioxidant (total thiols) and detoxifying enzyme activities (glutathione-S-transferase NADH quinone oxidoreductase) in DM-treated animals, indicated that beneficial effects were attributable, at least in part, to the activation of nuclear factor 2 erythroid-related factor 2 pathway. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.","title":"Diet supplementation with donkey milk upregulates liver mitochondrial uncoupling, reduces energy efficiency and improves antioxidant and antiinflam..."},{"docid":"MED-2052","text":"The addition of direct-acting antivirals (DAAs) to hepatitis C virus (HCV) treatment regimens has made treatment more effective and patient management more complex. Shepherding patients through a full course of HCV therapy requires motivation and involvement on the part of the patient and the physician. Indeed, physician inexperience and lack of confidence in guiding patients through the challenges of treatment appears to be a primary reason for early discontinuation of therapy. Among the many complications of HCV treatment that must be managed efficiently and effectively are depression and other psychiatric disorders; hematologic abnormalities including DAA- and ribavirin-associated anemia and peginterferon alfa-associated neutropenia and thrombocytopenia; rash and drug eruptions, including telaprevir-associated rash; and weight loss. Practical considerations in management of these common complications are offered. This article summarizes a presentation by Kenneth E. Sherman, MD, PhD, at the IAS-USA live continuing medical education course held in New York in June 2012.","title":"Managing adverse effects and complications in completing treatment for hepatitis C virus infection."},{"docid":"MED-4969","text":"Transmission of viruses, bacteria, and parasites to food by way of improperly washed hands is a major contributing factor in the spread of foodborne illnesses. Field observers have assessed compliance with hand washing regulations, yet few studies have included consideration of frequency and methods used by sectors of the food service industry or have included benchmarks for hand washing. Five 3-h observation periods of employee (n = 80) hand washing behaviors during menu production, service, and cleaning were conducted in 16 food service operations for a total of 240 h of direct observation. Four operations from each of four sectors of the retail food service industry participated in the study: assisted living for the elderly, childcare, restaurants, and schools. A validated observation form, based on 2005 Food Code guidelines, was used by two trained researchers. Researchers noted when hands should have been washed, when hands were washed, and how hands were washed. Overall compliance with Food Code recommendations for frequency during production, service, and cleaning phases ranged from 5% in restaurants to 33% in assisted living facilities. Procedural compliance rates also were low. Proposed benchmarks for the number of times hand washing should occur by each employee for each sector of food service during each phase of operation are seven times per hour for assisted living, nine times per hour for childcare, 29 times per hour for restaurants, and 11 times per hour for schools. These benchmarks are high, especially for restaurant employees. Implementation would mean lost productivity and potential for dermatitis; thus, active managerial control over work assignments is needed. These benchmarks can be used for training and to guide employee hand washing behaviors.","title":"Hand washing frequencies and procedures used in retail food services."},{"docid":"MED-1638","text":"OBJECTIVE: Migratory capacity of endothelial progenitor cells (EPCs) and mature endothelial cells (ECs) is a key prerequisite for endothelial repair after denuding injury or endothelial damage. METHODS AND RESULTS: We demonstrate that caffeine in physiologically relevant concentrations (50 to 100 micromol/L) induces migration of human EPCs as well as mature ECs. In patients with coronary artery disease (CAD), caffeinated coffee increased caffeine serum concentration from 2 micromol/L to 23 micromol/L, coinciding with a significant increase in migratory activity of patient-derived EPCs. Decaffeinated coffee neither affected caffeine serum levels nor migratory capacity of EPCs. Treatment with caffeine for 7 to 10 days in a mouse-model improved endothelial repair after denudation of the carotid artery. The enhancement of reendothelialization by caffeine was significantly reduced in AMPK knockout mice compared to wild-type animals. Transplantation of wild-type and AMPK(-/-) bone marrow into wild-type mice revealed no difference in caffeine challenged reendothelialization. ECs which were depleted of mitochondrial DNA did not migrate when challenged with caffeine, suggesting a potential role for mitochondria in caffeine-dependent migration. CONCLUSIONS: These results provide evidence that caffeine enhances endothelial cell migration and reendothelialization in part through an AMPK-dependent mechanism, suggesting a beneficial role for caffeine in endothelial repair.","title":"Caffeine enhances endothelial repair by an AMPK-dependent mechanism."},{"docid":"MED-2585","text":"Inositol hexaphosphate (IP6) is a naturally occurring polyphosphorylated carbohydrate that is present in substantial amounts in almost all plant and mammalian cells. It was recently recognized to possess multiple biological functions. A striking anticancer effect of IP6 was demonstrated in different experimental models. Inositol is also a natural constituent possessing moderate anticancer activity. The most consistent and best anticancer results were obtained from the combination of IP6 plus inositol. In addition to reducing cell proliferation, IP6 increases differentiation of malignant cells, often resulting in a reversion to normal phenotype. Exogenously administered IP6 is rapidly taken into the cells and dephosphorylated to lower-phosphate inositol phosphates, which further interfere with signal transduction pathways and cell cycle arrest. Enhanced immunity and antioxidant properties can also contribute to tumor cell destruction. However, the molecular mechanisms underlying this anticancer action are not fully understood. Because it is abundantly present in regular diet, efficiently absorbed from the gastrointestinal tract, and safe, IP6 holds great promise in our strategies for the prevention and treatment of cancer. IP6 plus inositol enhances the anticancer effect of conventional chemotherapy, controls cancer metastases, and improves the quality of life, as shown in a pilot clinical trial. The data strongly argue for the use of IP6 plus inositol in our strategies for cancer prevention and treatment. However, the effectiveness and safety of IP6 plus inositol at therapeutic doses needs to be determined in phase I and phase II clinical trials in humans.","title":"Cancer inhibition by inositol hexaphosphate (IP6) and inositol: from laboratory to clinic."},{"docid":"MED-4226","text":"Bone, as well as liver and lung, is one of the most preferential metastatic target sites for cancers including breast, prostate, and lung cancers and the consequences are always devastating. Like other metastasis, breast cancer bone metastasis consists of several steps from the escape of primary site to the colonization in target site. This review focuses on several key steps including: 1. Invasion and escape from primary tumor site. 2. Target migration toward bone. 3. Specific adhesion and arrest in bone. 4. Establishment of metastasis in bone. The factors involved in this process will provide good targets for therapy. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.","title":"Mechanisms of breast cancer bone metastasis."},{"docid":"MED-5120","text":"Human gammadeltaT lymphocytes are a subset of T cells and are a first line of defense against microbes and tumors. These gammadeltaT cells can be primed by nitrogen-containing bisphosphonates, and certain short-chain alkylamines. These primed gammadeltaT cells have an enhanced capacity to proliferate and to secrete cytokines upon ex vivo exposure to a wide variety of microbes and tumor cells. The largest dietary source of alkylamines is L-theanine, an amino acid unique to tea beverages that is catabolized to ethylamine. Supplementation of subjects with capsules containing L-theanine and catechins has recently been shown to decrease the incidence of cold and flu symptoms, while enhancing gammadeltaT cell function.","title":"L-theanine intervention enhances human gammadeltaT lymphocyte function."}],"string":"[\n {\n \"docid\": \"MED-3378\",\n \"text\": \"BACKGROUND AND OBJECTIVE: In 1981, a Petrol-Lead Phase-Out Program (PLPOP) was launched in Taiwan for the abatement of environmental lead emissions. The present study was intended to examine whether the high Petrol-Lead Emission Areas (PLEA) would result in an increase in the incidence rate of brain cancer based on a national data bank. METHODS: The national brain cancer incidence data was obtained from the Taiwan National Cancer Registry. Age standardized incidence rates were calculated based on the 2000 WHO world standard population, and gasoline consumption data was obtained from the Bureau of Energy. The differences in the trend tests for age-standardized incidence rates of brain cancer between high, median, low, and small PLEA were analyzed. RESULTS: A significant increase was found from small to high PLEA in age-standardized incidence rates of brain cancer. By taking six possible confounders into account, the age-standardized incidence rates for brain cancer were highly correlated with the median and high PLEA by reference to the small PLEA. CONCLUSION: After being adjusted for a number of relevant confounders, it could be concluded that high PLEA might result in an increase in the incidence rate of brain cancer resulting from high lead exposures. Copyright © 2011 Elsevier Ltd. All rights reserved.\",\n \"title\": \"Brain cancer associated with environmental lead exposure: evidence from implementation of a National Petrol-Lead Phase-Out Program (PLPOP) in Taiwa...\"\n },\n {\n \"docid\": \"MED-2461\",\n \"text\": \"This study aimed to evaluate the association of diet with respiratory symptoms and asthma in schoolchildren in Taipei, Taiwan. An in-class interview survey elicited experiences of asthma and respiratory symptoms and consumption frequencies of the major food categories in 2290 fifth graders. Respiratory symptoms surveyed included persistent cough, chest tightness, wheezing with cold, wheezing without cold, dyspnea-associated wheezing, and exercise-induced cough or wheezing. Results showed that the consumption of sweetened beverages had the strongest association with respiratory symptoms and was positively associated with six of the seven respiratory symptoms (all p < 0.05). The adjusted odds ratios (aOR) ranged from 1.05 (95% confidence interval (CI = 1.01-1.09) for exercise-induced cough to 1.09 (95% CI = 1.03-1.16) for wheezing without cold. Egg consumption was associated with 5 of the 7 respiratory symptoms. Consumptions of seafood, soy products, and fruits were each negatively associated with one of the seven respiratory symptoms (all p < 0.05). Consumption of seafood was negatively associated with physician-diagnosed asthma and consumptions of sweetened beverages and eggs were positively associated with suspected asthma (p < 0.05). In conclusion, the study suggests that diet is associated with the respiratory symptoms in schoolchildren in Taipei. Consumptions of sweetened beverages and eggs are associated with increased risk of respiratory symptoms and asthma whereas consumptions of soy products and fruits are associated with reduced risk of respiratory symptoms.\",\n \"title\": \"The association of diet with respiratory symptoms and asthma in schoolchildren in Taipei, Taiwan.\"\n },\n {\n \"docid\": \"MED-118\",\n \"text\": \"The aims of this study were to determine the concentrations of 4-nonylphenol (NP) and 4-octylphenol (OP) in 59 human milk samples and to examine related factors including mothers' demographics and dietary habits. Women who consumed over the median amount of cooking oil had significantly higher OP concentrations (0.98 ng/g) than those who consumed less (0.39 ng/g) (P < 0.05). OP concentration was significantly associated with the consumption of cooking oil (beta = 0.62, P < 0.01) and fish oil capsules (beta = 0.39, P < 0.01) after adjustment for age and body mass index (BMI). NP concentration was also significantly associated with the consumption of fish oil capsules (beta = 0.38, P < 0.01) and processed fish products (beta = 0.59, P < 0.01). The food pattern of cooking oil and processed meat products from factor analysis was strongly associated with OP concentration in human milk (P < 0.05). These determinations should aid in suggesting foods for consumption by nursing mothers in order to protect their infants from NP/OP exposure. 2010 Elsevier Ltd. All rights reserved.\",\n \"title\": \"Alkylphenols in human milk and their relations to dietary habits in central Taiwan.\"\n },\n {\n \"docid\": \"MED-2651\",\n \"text\": \"The aims of this study were to determine the concentrations of 4-nonylphenol (NP) and 4-octylphenol (OP) in 59 human milk samples and to examine related factors including mothers' demographics and dietary habits. Women who consumed over the median amount of cooking oil had significantly higher OP concentrations (0.98 ng/g) than those who consumed less (0.39 ng/g) (P < 0.05). OP concentration was significantly associated with the consumption of cooking oil (beta = 0.62, P < 0.01) and fish oil capsules (beta = 0.39, P < 0.01) after adjustment for age and body mass index (BMI). NP concentration was also significantly associated with the consumption of fish oil capsules (beta = 0.38, P < 0.01) and processed fish products (beta = 0.59, P < 0.01). The food pattern of cooking oil and processed meat products from factor analysis was strongly associated with OP concentration in human milk (P < 0.05). These determinations should aid in suggesting foods for consumption by nursing mothers in order to protect their infants from NP/OP exposure. 2010 Elsevier Ltd. All rights reserved.\",\n \"title\": \"Alkylphenols in human milk and their relations to dietary habits in central Taiwan.\"\n },\n {\n \"docid\": \"MED-1613\",\n \"text\": \"The present study was designed to examine the effects of habitual consumption of Taiwanese vegetarian diets on hormonal secretion, and on lipid and glycaemic control. Of the ninety-eight healthy female adults recruited from Hualien, Taiwan (aged 31-45 years), forty-nine were Buddhist lactovegetarians and forty-nine were omnivores. Dietary intakes were measured, and blood levels of nutrients and hormones were analysed. Vegetarians consumed less energy, fat and protein, but more fibre than the omnivores. Compared with the omnivores, the vegetarians had, on average, lower BMI and smaller waist circumference. Except for slightly lower levels of thyroxine (T4) in vegetarians, vegetarians and omnivores both showed similar levels of triiodothyronine (T3), free T4, thyroid-stimulating hormone, T3:T4 ratio and cortisol. Compared with the omnivores, the vegetarians had significantly lower levels of fasting insulin (median: 35.3 v. 50.6 pmol/l) and plasma glucose (mean: 4.7 (se 0.05) v. 4.9 (se 0.05) mmol/l). Insulin resistance, as calculated by the homeostasis model assessment method, was significantly lower in the vegetarians than in the omnivores (median: 1.10 v. 1.56), while beta-cell function was not different between the two groups. BMI and diet were both independent predictors for insulin resistance, and contributed 18 and 15 % of the variation in insulin resistance, respectively. In conclusion, Taiwanese vegetarians had lower glucose and insulin levels and higher insulin sensitivity than did the omnivores. Diet and lower BMI were partially responsible for the high insulin sensitivity observed in young Taiwanese vegetarians.\",\n \"title\": \"Taiwanese vegetarians have higher insulin sensitivity than omnivores.\"\n },\n {\n \"docid\": \"MED-3947\",\n \"text\": \"Hibiscus sabdariffa Linne (Malvaceae), an attractive plant believed to be native to Africa, is cultivated in the Sudan and Eastern Taiwan. Anthocyanins exist widely in many vegetables and fruits. Some reports demonstrated that anthocyanins extracted from H. sabdariffa L., Hibiscus anthocyanins (HAs) (which are a group of natural pigments existing in the dried calyx of H. sabdariffa L.) exhibited antioxidant activity and liver protection. Therefore, in this study, we explored the effect of HAs on human cancer cells. The result showed that HAs could cause cancer cell apoptosis, especially in HL-60 cells. Using flow cytometry, we found that HAs treatment (0-4 mg/ml) markedly induced apoptosis in HL-60 cells in a dose- and time-dependent manner. The result also revealed increased phosphorylation in p38 and c-Jun, cytochrome c release, and expression of tBid, Fas, and FasL in the HAs-treated HL-60 cells. We further used SB203580 (p38 inhibitor), PD98059 (MEK inhibitor), SP600125 (JNK inhibitor), and wortmannin (phosphatidylinositol 3-kinase; PI-3K inhibitor) to evaluate their effect on the HAs-induced HL-60 death. The data showed that only SB203580 had strong potential in inhibiting HL-60 cell apoptosis and related protein expression and phosphorylation. Therefore, we suggested that HAs mediated HL-60 apoptosis via the p38-FasL and Bid pathway. According to these results, HAs could be developed as chemopreventive agents. However, further investigations into the specificity and mechanism(s) of HAs are needed.\",\n \"title\": \"Hibiscus anthocyanins rich extract-induced apoptotic cell death in human promyelocytic leukemia cells.\"\n },\n {\n \"docid\": \"MED-3681\",\n \"text\": \"OBJECTIVE: To determine the effects of the probiotic lactic acid bacterium, Lactobacillus rhamnosus HN001, on natural cellular immunity when delivered orally in normal low-fat milk (LFM) or lactose-hydrolyzed low-fat milk (LFM-LH). DESIGN: A three stage, pre-post intervention trial, spanning nine weeks. SETTING: Taipei Medical College Hospital, Taipei, Taiwan. SUBJECTS: Fifty-two healthy middle-aged and elderly volunteers (17 males, 35 females; median age 63.5, range 44-80). INTERVENTIONS: Stage 1 (run-in diet): 25 g/200 mL reconstituted LFM powder, twice daily for 3 weeks. Stage 2 (probiotic intervention): LFM or LFM-LH, supplemented with 10(9) CFUs/g L. rhamnosus HN001 in each case, for 3 weeks. Stage 3 (wash-out): LFM for 3 weeks. MEASURES OF OUTCOME: In vitro phagocytic capacity of peripheral blood polymorphonuclear (PMN) leukocytes; in vitro tumoricidal activity of natural killer (NK) leukocytes. RESULTS: Immunological responses were unaffected by the run-in diet of LFM alone. In contrast, the relative proportion of PMN cells showing phagocytic activity increased by 19% and 15%, respectively, following consumption of HN001 in either LFM or LFM-LH; the relative level of NK cell tumor killing activity increased by 71% and 147%. In most cases these levels declined following cessation, but remained above baseline. CONCLUSIONS: Dietary consumption of L. rhamnosus HN001, in a base of low-fat milk or lactose-hydrolyzed low-fat milk, appears to enhance systemic cellular immune responses and may be useful as a dietary supplement to boost natural immunity.\",\n \"title\": \"Systemic immunity-enhancing effects in healthy subjects following dietary consumption of the lactic acid bacterium Lactobacillus rhamnosus HN001.\"\n },\n {\n \"docid\": \"MED-4832\",\n \"text\": \"Cardiovascular disease (CVD) is the most important adult health problem in the world. Epidemiological studies and laboratory experiments have shown that fruit and vegetable consumption has protective effects against CVD. The purpose of the study was to investigate the effects of consumption of two kiwifruit per day on the lipid profile, antioxidants and markers of lipid peroxidation in hyperlipidemic adult men and women in Taiwan. Forty-three subjects who had hyperlipidemia, including 13 males and 30 females, participated in this study. They were asked to consume two kiwifruit per day for 8 weeks. Anthropometric measurements were made. Before the intervention and at 4 and 8 weeks of the intervention, fasting blood samples were analyzed for total cholesterol, triacylglycerol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein cholesterol (HDL-C). Additionally vitamin E and vitamin C, the malondialdehyde + 4-hydroxy-2(E)-nonenal concentration, and the lag time of LDL oxidation were determined. No significant differences from baseline to 8 weeks of the intervention were detected for triacylglycerol, total cholesterol, or LDL cholesterol. However, after 8 weeks of consumption of kiwifruit, the HDL-C concentration was significantly increased and the LDL cholesterol/HDL-C ratio and total cholesterol/HDL-C ratio were significantly decreased. Vitamin C and vitamin E also increased significantly. In addition, the lag time of LDL oxidation and malondialdehyde + 4-hydroxy-2(E)-nonenal had significantly changed at 4 and 8 weeks during the kiwifruit intervention. Regular consumption of kiwifruit might exert beneficial effects on the antioxidative status and the risk factors for CVD in hyperlipidemic subjects.\",\n \"title\": \"Effects of kiwifruit consumption on serum lipid profiles and antioxidative status in hyperlipidemic subjects.\"\n },\n {\n \"docid\": \"MED-4093\",\n \"text\": \"OBJECTIVE: The association between hyperuricemia and cardiovascular events has been documented in high-risk groups, but is still undetermined in general populations, especially Chinese. This study assessed the temporal association between serum uric acid level, hyperuricemia, and cardiovascular mortality. METHODS: A prospective cohort study of 41,879 men and 48,514 women ages > or = 35 years was conducted using data from the MJ Health Screening Centers in Taiwan. Mortality from all causes, total cardiovascular disease (CVD), ischemic stroke, congestive heart failure, hypertensive disease, and coronary heart disease were compared according to increasing serum uric acid levels. RESULTS: A total of 1,151 (21.2%) events of 5,427 total deaths were ascribed to CVD (mean followup 8.2 years). Hazard ratios (HRs) for hyperuricemia (serum uric acid level >7 mg/dl) were estimated with Cox regression model after adjusting for age, sex, body mass index, cholesterol, triglycerides, diabetes, hypertension, heavy cigarette smoking, and frequent alcohol consumption. In all patients, HRs were 1.16 (P < 0.001) for all-cause mortality, 1.39 (P < 0.001) for total CVD, and 1.35 (P = 0.02) for ischemic stroke. In subgroup analysis, the HRs for cardiovascular risk remained significant in patients with hypertension (1.44, P < 0.001) and in patients with diabetes (1.64, P < 0.001). In addition, in a low metabolic risk subgroup, the HRs for all-cause mortality and total cardiovascular morbidity were 1.24 (P = 0.02) and 1.48 (P = 0.16), respectively. CONCLUSION: Hyperuricemia was an independent risk factor of mortality from all causes, total CVD, and ischemic stroke in the Taiwanese general population, in high-risk groups, and potentially in low-risk groups.\",\n \"title\": \"Serum uric acid level as an independent risk factor for all-cause, cardiovascular, and ischemic stroke mortality: a Chinese cohort study.\"\n },\n {\n \"docid\": \"MED-3435\",\n \"text\": \"INTRODUCTION: Previous cross-sectional studies have suggested that erectile dysfunction (ED) represents an independent risk factor for future cardiovascular events. However, very few studies have attempted to examine the association between ED and subsequent stroke. AIM: The aim of this study is to estimate the risk of stroke during a 5-year follow-up period after the first ambulatory care visit for the treatment of ED using nationwide, population-based data and a retrospective case-control cohort design in Taiwan. METHODS: This study used data sourced from the \\\"Longitudinal Health Insurance Database.\\\" The study cohort comprised 1,501 patients who received a principal diagnosis of ED between 1997 and 2001 and 7,505 randomly selected subjects as the comparison cohort. Each patient (N = 9,006) was then individually tracked for 5 years from their index ambulatory care visit to identify those who had diagnosed episodes of stroke. MAIN OUTCOME MEASURE: Stratified Cox proportional hazard regressions were performed as a means of comparing the 5-year stroke-free survival rate for the two cohorts. RESULTS: Of the sampled patients, 918 (10.2%) developed stroke within the 5-year follow-up period, that is, 188 individuals (12.5% of the patients with ED) from the study cohort and 730 individuals (9.7% of patients in the comparison cohort) from the comparison cohort. The log-rank test indicated that patients with ED had significantly lower 5-year stroke-free survival rates than those in the comparison cohort (P < 0.001). After adjusting for the patient's monthly income, geographical location, hypertension, diabetes, coronary heart disease, peripheral vascular disease, atrial fibrillation, and hyperlipidemia, patients with ED were more likely to have a stroke during the 5-year follow-up period than patients in the comparison cohort (hazard ratio = 1.29, 95% confidence interval = 1.08 - 1.54, P < 0.01). CONCLUSIONS: These results suggest that ED is a surrogate marker for future stroke in men. © 2010 International Society for Sexual Medicine.\",\n \"title\": \"Increased risk of stroke among men with erectile dysfunction: a nationwide population-based study.\"\n },\n {\n \"docid\": \"MED-931\",\n \"text\": \"This study evaluated the toxicological sensitivity of non-feeding larval stages of a key Antarctic species (Antarctic krill, Euphausia superba) to p,p'-dichlorodiphenyl dichloroethylene (p,p'-DDE) exposure. The aqueous uptake clearance rate of 84 mL g(-1) preserved weight (p.w.) h(-1) determined for p,p'-DDE in Antarctic krill larvae is comparable to previous findings for small cold water crustaceans and five times slower than the rates reported for an amphipod inhabiting warmer waters. Natural variations in larval physiology appear to influence contaminant uptake and larval krill behavioural responses, strongly highlighting the importance of time of measurement for ecotoxicological testing. Sublethal narcosis (immobility) was observed in larval Antarctic krill from p,p'-DDE body residues of 0.2 mmol/kg p.w., which is in agreement with findings for adult krill and temperate aquatic species. The finding of comparable body residue-based toxicity of p,p'-DDE between polar and temperate species supports the tissue residue approach for environmental risk assessment of polar ecosystems. Copyright © 2011 Elsevier Ltd. All rights reserved.\",\n \"title\": \"Aqueous uptake and sublethal toxicity of p,p'-DDE in non-feeding larval stages of Antarctic krill (Euphausia superba).\"\n },\n {\n \"docid\": \"MED-3371\",\n \"text\": \"Background: The overconsumption of energy-dense foods leads to excessive energy intakes. The substitution of low-energy-dense vegetables for foods higher in energy density can help decrease energy intakes but may be difficult to implement if individuals dislike the taste of vegetables. Objective: We investigated whether incorporating puréed vegetables to decrease the energy density of entrées at multiple meals reduced daily energy intakes and increased daily vegetable intakes. Design: In this crossover study, 20 men and 21 women ate ad libitum breakfast, lunch, and dinner in the laboratory once a week for 3 wk. Across conditions, entrées at meals varied in energy density from standard versions (100% condition) to reduced versions (85% and 75% conditions) by the covert incorporation of 3 or 4.5 times the amount of puréed vegetables. Entrées were accompanied by unmanipulated side dishes. Participants rated their hunger and fullness before and after meals. Results: Subjects consumed a consistent weight of foods across conditions of energy density; thus, the daily energy intake significantly decreased by 202 ± 60 kcal in the 85% condition (P < 0.001) and by 357 ± 47 kcal in the 75% condition (P < 0.0001). Daily vegetable consumption significantly increased from 270 ± 17 g of vegetables in the 100% condition to 487 ± 25 g of vegetables in the 75% condition (P < 0.0001). Despite the decreased energy intake, ratings of hunger and fullness did not significantly differ across conditions. Entrées were rated as similar in palatability across conditions. Conclusions: Large amounts of puréed vegetables can be incorporated into various foods to decrease the energy density. This strategy can lead to substantial reductions in energy intakes and increases in vegetable intakes. This trial was registered at clinicaltrials.gov as NCT01165086.\",\n \"title\": \"Hidden vegetables: an effective strategy to reduce energy intake and increase vegetable intake in adults\"\n },\n {\n \"docid\": \"MED-1218\",\n \"text\": \"There has been a recent increase in community-associated infections linked to methicillin-resistant Staphylococcus aureus (MRSA) and Clostridium difficile. It is established that both pathogens can be recovered from retail pork, although it is unclear to what degree contamination is acquired at the farm in comparison to that acquired during processing. To address this gap, the following study reports on the carriage of MRSA and C. difficile on pigs from birth through to the end of processing. C. difficile was isolated from 28 (93%) of 30 pigs at 1 day of age, but prevalence declined sharply to 1 of 26 by market age (188 days). MRSA prevalence peaked at 74 days of age, with 19 (68%) of 28 pigs testing positive, but declined to 3 of 26 at 150 days of age, with no pig being detected as positive at market age. At the processing facility, C. difficile was isolated from the holding area, with a single carcass testing positive for the pathogen at preevisceration. MRSA was primarily isolated from nasal swabs with 8 (31%) carcasses testing positive at postbleed, which increased to 14 (54%) positive at postscald tanks. Only one carcass (sampled at postbleed) tested positive for MRSA, with no recovery of the pathogen from environmental samples taken. C. difficile ribotype 078 predominated in the longitudinal portion of the study, accounting for all of the 68 isolates recovered from pigs. Only three C. difficile isolates, which were identified as ribotype 078, were recovered at the slaughterhouse. MRSA spa type 539 (t034) predominated in pigs on the farm and samples taken at the slaughterhouse, accounting for 80% of all isolates recovered. The study demonstrated that both C. difficile and MRSA acquired on the farm can be transferred through to processing, although no evidence for significant cross-contamination between carcasses or the slaughterhouse environment was evident.\",\n \"title\": \"Longitudinal study of Clostridium difficile and Methicillin-resistant Staphylococcus aureus associated with pigs from weaning through to the end of...\"\n },\n {\n \"docid\": \"MED-2972\",\n \"text\": \"BACKGROUND: Elevated levels of lipids, such as total cholesterol (TC), low-density lipoprotein cholesterol (LDL), and triglycerides (TG), are widely recognized as risk factors for cardiovascular disease (CVD). Oxidized LDL (OxLDL) is an emerging risk factor considered relevant in oxidative stress and endothelial dysfunction, which is implicated in the progression of CVD. Consumption of a diet rich in polyphenols may be cardioprotective through its impact on oxidative stress and protecting LDL from oxidation. OBJECTIVES: This study was designed to test the ability of strawberry phenolic compounds to mitigate the postprandial effects of a high-fat meal on OxLDL as well as investigate the effects of phenolic compounds on lipid metabolism. METHODS: Twenty-four hyperlipidemic men and women (14 women, 10 men; mean age 50.9 +/- SD 15 years) were recruited to participate in this randomized, single-blind, placebo-controlled, 12-wk crossover trial. After a 10-day run-in period, subjects consumed either an active strawberry beverage (Str; containing 10 g freeze-dried fruit) or a placebo (Pbo) beverage matched in energy and macronutrient composition for 6 weeks. Twice before randomization and once at the 6-week crossover point, subjects received either Str or Pbo with a high-fat challenge meal (HFM). TC, LDL, high-density lipoprotein cholesterol, TG, and OxLDL were measured at defined intervals for 6 h before and after HFM challenge. Fasting concentrations of blood variables at 0, 6, and 12 weeks were compared to assess chronic intake of Str or Pbo. RESULTS: After the HFM during the run-in period, TG and OxLDL were lower after Str than Pbo (p = 0.005, p = 0.01, and p = 0.0008, respectively). HFM responses after 6 weeks of Str versus Pbo resulted in decreased lipid levels and a sex by treatment interaction for OxLDL (p = < 0.0001, and p = 0.0002). CONCLUSION: The present results support a role for strawberry in mitigating fed-state oxidative stressors that may contribute to atherogenesis.\",\n \"title\": \"Strawberry modulates LDL oxidation and postprandial lipemia in response to high-fat meal in overweight hyperlipidemic men and women.\"\n },\n {\n \"docid\": \"MED-3161\",\n \"text\": \"Intense exercise is directly related to muscular damage and oxidative stress due to excessive reactive oxygen species (ROS) in both, plasma and white blood cells. Nevertheless, exercise-derived ROS are essential to regulate cellular adaptation to exercise. Studies on antioxidant supplements have provided controversial results. The purpose of this study was to determine the effect of moderate antioxidant supplementation (lemon verbena extract) in healthy male volunteers that followed a 90-min running eccentric exercise protocol for 21 days. Antioxidant enzymes activities and oxidative stress markers were measured in neutrophils. Besides, inflammatory cytokines and muscular damage were determined in whole blood and serum samples, respectively. Intense running exercise for 21 days induced antioxidant response in neutrophils of trained male through the increase of the antioxidant enzymes catalase, glutathione peroxidase and glutathione reductase. Supplementation with moderate levels of an antioxidant lemon verbena extract did not block this cellular adaptive response and also reduced exercise-induced oxidative damage of proteins and lipids in neutrophils and decreased myeloperoxidase activity. Moreover, lemon verbena supplementation maintained or decreased the level of serum transaminases activity indicating a protection of muscular tissue. Exercise induced a decrease of interleukin-6 and interleukin-1β levels after 21 days measured in basal conditions, which was not inhibited by antioxidant supplementation. Therefore, moderate antioxidant supplementation with lemon verbena extract protects neutrophils against oxidative damage, decreases the signs of muscular damage in chronic running exercise without blocking the cellular adaptation to exercise.\",\n \"title\": \"Effect of lemon verbena supplementation on muscular damage markers, proinflammatory cytokines release and neutrophils' oxidative stress in chronic ...\"\n },\n {\n \"docid\": \"MED-3981\",\n \"text\": \"The aim of this study was to investigate the relationship between child characteristics, parental and environmental factors and the occurrence of acute respiratory illness (ARI) and acute otitis media (AOM) among Finnish children attending day care centres (DCCs). The study was a cross-sectional questionnaire of 594 children aged 1-6 y from 18 DCCs in Helsinki, Finland. Recurrent (> or =4 diseases/y) ARI was present in 44% of the 1-3-y-olds and 23% of the 4-6-y-olds, and recurrent AOM in 15% and 2.5%, respectively. Parent atopic disease (odds ratio (OR) 1.53, p = 0.033), mother's academic education (OR 1.77, p = 0.008) and a medium length of DCC attendance compared to a short period (OR 1.67, p = 0.049) increased, while furry pets (OR 0.44, p = 0.003) and older child age (OR 0.38, p < 0.001) reduced the risk of recurrent ARI. Recurrent ARI (OR 3.96, p = 0.008), mother's academic education (OR 5.02, p = 0.003), and a medium length of DCC attendance compared to a short period (OR 3.34, p = 0.044) increased, while partial breastfeeding > or =6 months (OR 0.20, p = 0.002) and older child age (OR 0.05, p < 0.001) reduced the risk of recurrent AOM. Parental and environmental factors had a significant impact on recurrent ARI and AOM episodes in children attending DCCs. These risk factors should be considered in future studies intending to reduce DCC infections.\",\n \"title\": \"Factors associated with acute respiratory illness in day care children.\"\n },\n {\n \"docid\": \"MED-2469\",\n \"text\": \"The intestinal flora is considered to have an impact on the development of the immune system. In the anthroposophic lifestyle, a diet comprising vegetables spontaneously fermented by lactobacilli, and a restrictive use of antibiotics, anti-pyretics and vaccinations, is typical. The aim of this study was to assess the gut flora in infants in relation to certain lifestyle characteristics associated with anthroposophy. Sixty-nine children < 2 years of age with an anthroposophic lifestyle, and 59 infants of a similar age with a traditional lifestyle, were clinically examined and questionnaire replies assessed. Fecal samples were analyzed by bacterial enumeration, bacterial typing through biochemical fingerprinting and by measuring microflora-associated characteristics (MACs). The numbers of colony-forming units (CFU)/g of feces were significantly higher for enterococci and lactic acid bacteria in children who had never been exposed to antibiotics (5.5 x 107 vs. 2.1 x 107; p < 0.001 and 10 x 107 vs. 4.1 x 107; p < 0.01, respectively). Furthermore, the number of enterococci was significantly higher in breastfed and vegetarian infants (p < 0.01). The diversity (Simpson's diversity index) of lactobacilli, as determined by biochemical fingerprinting, was higher in infants born at home than in those born in hospital (p < 0.01). Several MACs were related to specific lifestyle features, and infants with an anthroposophic lifestyle had a higher proportion of acetic acid and a lower proportion of propionic acid in their stool as compared to the control children. In conclusion, lifestyle factors related to the anthroposophic way of life influenced the composition of the gut flora in the infants. These differences may contribute to the lower prevalence of atopic disease previously observed in children in anthroposophic families.\",\n \"title\": \"An anthroposophic lifestyle and intestinal microflora in infancy.\"\n },\n {\n \"docid\": \"MED-870\",\n \"text\": \"Ilex paraguariensis dried and minced leaves are made into a brewed tea, prepared in a sui generis manner by large populations in South America, having evolved from a tea drunk by the Guarani ethnic group to a beverage that has a social and almost ritualistic role in some South American modern societies. It is used both as a source of caffeine, in lieu or in parallel with tea and coffee, but also as a therapeutic agent for its alleged pharmacological properties. Although with some exceptions, research on biomedical properties of this herb has had a late start and strongly lags behind the impressive amount of literature on green tea and coffee. However, in the past 15 years, there was a several-fold increase in the literature studying Ilex paraguariensis properties showing effects such as antioxidant properties in chemical models and ex vivo lipoprotein studies, vaso-dilating and lipid reduction properties, antimutagenic effects, controversial association with oropharyngeal cancer, anti-glycation effects and weight reduction properties. Lately, promising results from human intervention studies have surfaced and the literature offers several developments on this area. The aim of this review is to provide a concise summary of the research published in the past three years, with an emphasis on translational studies, inflammation and lipid metabolism. Ilex paraguariensis reduces LDL-cholesterol levels in humans with Ilex paraguariensis dyslipoproteinemia and the effect is synergic with that of statins. Plasma antioxidant capacity as well as expression of antioxidant enzymes is positively modulated by intervention with Ilex paraguariensis in human cohorts. A review on the evidence implicating Ilex paraguariensis heavy consumption with some neoplasias show data that are inconclusive but indicate that contamination with alkylating agents during the drying process of the leaves should be avoided. On the other hand, several new studies confirm the antimutagenic effects of Ilex paraguariensis in different models, from DNA double breaks in cell culture models to mice studies. Novel interesting work has emerged showing significant effect on weight reduction both in mice and in rat models. Some mechanisms involved are inhibition of pancreatic lipase, activation of AMPK and uncoupling of electron transport. Intervention studies in animals have provided strong evidence of anti-inflammatory effects of Ilex paraguariensis, notably protecting cigarette-induced lung inflammation acting on macrophage migration and inactivating matrix-metalloproteinase. Research on the effects of Ilex paraguariensis in health and disease has confirmed its antioxidant, anti-inflammatory, antimutagenic and lipid-lowering activities. Although we are still waiting for the double-blind, randomized prospective clinical trial, the evidence seems to provide support for beneficial effects of mate drinking on chronic diseases with inflammatory component and lipid metabolism disorders. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.\",\n \"title\": \"Recent advances on Ilex paraguariensis research: minireview.\"\n },\n {\n \"docid\": \"MED-1151\",\n \"text\": \"Background: Organically produced foods are less likely than conventionally produced foods to contain pesticide residues. Methods: We examined the hypothesis that eating organic food may reduce the risk of soft tissue sarcoma, breast cancer, non-Hodgkin lymphoma and other common cancers in a large prospective study of 623 080 middle-aged UK women. Women reported their consumption of organic food and were followed for cancer incidence over the next 9.3 years. Cox regression models were used to estimate adjusted relative risks for cancer incidence by the reported frequency of consumption of organic foods. Results: At baseline, 30%, 63% and 7% of women reported never, sometimes, or usually/always eating organic food, respectively. Consumption of organic food was not associated with a reduction in the incidence of all cancer (n=53 769 cases in total) (RR for usually/always vs never=1.03, 95% confidence interval (CI): 0.99–1.07), soft tissue sarcoma (RR=1.37, 95% CI: 0.82–2.27), or breast cancer (RR=1.09, 95% CI: 1.02–1.15), but was associated for non-Hodgkin lymphoma (RR=0.79, 95% CI: 0.65–0.96). Conclusions: In this large prospective study there was little or no decrease in the incidence of cancer associated with consumption of organic food, except possibly for non-Hodgkin lymphoma.\",\n \"title\": \"Organic food consumption and the incidence of cancer in a large prospective study of women in the United Kingdom\"\n },\n {\n \"docid\": \"MED-4846\",\n \"text\": \"The effects of a strict uncooked vegan diet on serum lipid and sterol concentrations were studied in patients with rheumatoid arthritis. The subjects were randomized into a vegan diet group (n 16), who consumed a vegan diet for 2-3 months, or into a control group (n 13), who continued their usual omnivorous diets. Serum total and LDL-cholesterol and -phospholipid concentrations were significantly decreased by the vegan diet. The levels of serum cholestanol and lathosterol also decreased, but serum cholestanol:total cholesterol and lathosterol:total cholesterol did not change. The effect of a vegan diet on serum plant sterols was divergent as the concentration of campesterol decreased while that of sitosterol increased. This effect resulted in a significantly greater sitosterol:campesterol value in the vegan diet group than in the control group (1.48 (SD 0.39) v. 0.72 (SD 0.14); P < 0.001). A higher concentration of campesterol compared with sitosterol is normal in omnivorous subjects and can be explained by lower absorption and esterification rates of sitosterol. Our results suggest that a strict uncooked vegan diet changes the relative absorption rates of these sterols and/or their biliary clearance.\",\n \"title\": \"Divergent changes in serum sterols during a strict uncooked vegan diet in patients with rheumatoid arthritis.\"\n },\n {\n \"docid\": \"MED-2122\",\n \"text\": \"OBJECTIVE: To clarify the hormonal context of breast cancer etiology we used data from a large, population-based case-control study to investigate the relationship between breast cancer risk and a history of diabetes mellitus, disorders associated with estrogen stimulation (uterine fibroids, endometriosis, gallstones), and disorders associated with androgen stimulation (acne, hirsutism, and polycystic ovaries). METHODS: Breast cancer patients between 50 and 75 years old were identified from state-wide tumor registries in Wisconsin, Massachusetts, and New Hampshire; controls were randomly selected from drivers' license lists (age less than 65) or Medicare enrollment files (age 65-74). Information on reproductive history, medical history, and personal habits was obtained by telephone interview. A total of 5659 cases and 5928 controls were interviewed and provided suitable data. RESULTS: There was no overall association between breast cancer risk and reported history of diabetes mellitus, endometriosis, uterine fibroids, gallstones, or cholecystectomy. However, the disorders with androgenic associations all conferred an increased risk: the overall odds ratio (OR) for a history of acne was 1.4 (95% CI 1.0-1.9), that for hirsutism was 1.2 (95% CI 0.81-1.8), and that for polycystic ovaries 1.6 (95% CI 0.8-3.2). Diabetes mellitus diagnosed before age 35 conferred an odds ratio of 0.52 (95% 0.25-1.1), while diabetes diagnosed at a later age was associated with an increased risk (OR = 1.2, 95% CI 1.0-1.4). CONCLUSIONS: Androgen-related phenomena are likely to be important in the etiology of breast cancer.\",\n \"title\": \"Metabolic disorders and breast cancer risk (United States).\"\n },\n {\n \"docid\": \"MED-1338\",\n \"text\": \"Objective To examine whether high milk consumption is associated with mortality and fractures in women and men. Design Cohort studies. Setting Three counties in central Sweden. Participants Two large Swedish cohorts, one with 61 433 women (39-74 years at baseline 1987-90) and one with 45 339 men (45-79 years at baseline 1997), were administered food frequency questionnaires. The women responded to a second food frequency questionnaire in 1997. Main outcome measure Multivariable survival models were applied to determine the association between milk consumption and time to mortality or fracture. Results During a mean follow-up of 20.1 years, 15 541 women died and 17 252 had a fracture, of whom 4259 had a hip fracture. In the male cohort with a mean follow-up of 11.2 years, 10 112 men died and 5066 had a fracture, with 1166 hip fracture cases. In women the adjusted mortality hazard ratio for three or more glasses of milk a day compared with less than one glass a day was 1.93 (95% confidence interval 1.80 to 2.06). For every glass of milk, the adjusted hazard ratio of all cause mortality was 1.15 (1.13 to 1.17) in women and 1.03 (1.01 to 1.04) in men. For every glass of milk in women no reduction was observed in fracture risk with higher milk consumption for any fracture (1.02, 1.00 to 1.04) or for hip fracture (1.09, 1.05 to 1.13). The corresponding adjusted hazard ratios in men were 1.01 (0.99 to 1.03) and 1.03 (0.99 to 1.07). In subsamples of two additional cohorts, one in males and one in females, a positive association was seen between milk intake and both urine 8-iso-PGF2α (a biomarker of oxidative stress) and serum interleukin 6 (a main inflammatory biomarker). Conclusions High milk intake was associated with higher mortality in one cohort of women and in another cohort of men, and with higher fracture incidence in women. Given the observational study designs with the inherent possibility of residual confounding and reverse causation phenomena, a cautious interpretation of the results is recommended.\",\n \"title\": \"Milk intake and risk of mortality and fractures in women and men: cohort studies\"\n },\n {\n \"docid\": \"MED-762\",\n \"text\": \"The Ethiopian Field Epidemiology and Laboratory Training Program (EFELTP) is a comprehensive two-year competency-based training and service program designed to build sustainable public health expertise and capacity. Established in 2009, the program is a partnership between the Ethiopian Federal Ministry of Health, the Ethiopian Health and Nutrition Research Institute, Addis Ababa University School of Public Health, the Ethiopian Public Health Association and the US Centers of Disease Control and Prevention. Residents of the program spend about 25% of their time undergoing didactic training and the 75% in the field working at program field bases established with the MOH and Regional Health Bureaus investigating disease outbreaks, improving disease surveillance, responding to public health emergencies, using health data to make recommendations and undertaking other field Epidemiology related activities on setting health policy. Residents from the first 2 cohorts of the program have conducted more than 42 outbreaks investigations, 27analyses of surveillance data, evaluations of 11 surveillance systems, had28oral and poster presentation abstracts accepted at 10 scientific conferences and submitted 8 manuscripts of which 2are already published. The EFELTP has provided valuable opportunities to improve epidemiology and laboratory capacity building in Ethiopia. While the program is relatively young, positive and significant impacts are assisting the country better detect and respond to epidemics and address diseases of major public health significance.\",\n \"title\": \"The Ethiopian Field Epidemiology and Laboratory Training Program: strengthening public health systems and building human resource capacity.\"\n },\n {\n \"docid\": \"MED-2115\",\n \"text\": \"Dietary PUFA, mainly those of the n-3 family, are known to play essential roles in the maintenance of energy balance and in the reduction of body fat deposition through the upregulation of mitochondrial uncoupling that is the main source of reactive oxygen species. We hypothesized that rat supplementation with raw donkey's milk (DM), characterized by low-fat content and higher n3:n6 ratio, may affect energy balance, lipid metabolism, and prooxidant status as compared to animals treated with cow's milk. In the present study, the effects of drinking raw DM (for 4 weeks) on energy balance, lipid metabolism, antiinflammatory, and antioxidant/detoxifying defences was compared to that produced by rat intake of an iso-energetic amount of raw cow's milk. The hypolipidemic effect produced by DM paralleled with the enhanced mitochondrial activity/proton leakage and with the increased activity or expression of mitochondrial markers namely, carnitine palmitoyl transferase and uncoupling protein 2. The association of decreased energy efficiency with reduced proinflammatory signs (TNF-α and LPS levels) with the significant increase antioxidant (total thiols) and detoxifying enzyme activities (glutathione-S-transferase NADH quinone oxidoreductase) in DM-treated animals, indicated that beneficial effects were attributable, at least in part, to the activation of nuclear factor 2 erythroid-related factor 2 pathway. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.\",\n \"title\": \"Diet supplementation with donkey milk upregulates liver mitochondrial uncoupling, reduces energy efficiency and improves antioxidant and antiinflam...\"\n },\n {\n \"docid\": \"MED-2052\",\n \"text\": \"The addition of direct-acting antivirals (DAAs) to hepatitis C virus (HCV) treatment regimens has made treatment more effective and patient management more complex. Shepherding patients through a full course of HCV therapy requires motivation and involvement on the part of the patient and the physician. Indeed, physician inexperience and lack of confidence in guiding patients through the challenges of treatment appears to be a primary reason for early discontinuation of therapy. Among the many complications of HCV treatment that must be managed efficiently and effectively are depression and other psychiatric disorders; hematologic abnormalities including DAA- and ribavirin-associated anemia and peginterferon alfa-associated neutropenia and thrombocytopenia; rash and drug eruptions, including telaprevir-associated rash; and weight loss. Practical considerations in management of these common complications are offered. This article summarizes a presentation by Kenneth E. Sherman, MD, PhD, at the IAS-USA live continuing medical education course held in New York in June 2012.\",\n \"title\": \"Managing adverse effects and complications in completing treatment for hepatitis C virus infection.\"\n },\n {\n \"docid\": \"MED-4969\",\n \"text\": \"Transmission of viruses, bacteria, and parasites to food by way of improperly washed hands is a major contributing factor in the spread of foodborne illnesses. Field observers have assessed compliance with hand washing regulations, yet few studies have included consideration of frequency and methods used by sectors of the food service industry or have included benchmarks for hand washing. Five 3-h observation periods of employee (n = 80) hand washing behaviors during menu production, service, and cleaning were conducted in 16 food service operations for a total of 240 h of direct observation. Four operations from each of four sectors of the retail food service industry participated in the study: assisted living for the elderly, childcare, restaurants, and schools. A validated observation form, based on 2005 Food Code guidelines, was used by two trained researchers. Researchers noted when hands should have been washed, when hands were washed, and how hands were washed. Overall compliance with Food Code recommendations for frequency during production, service, and cleaning phases ranged from 5% in restaurants to 33% in assisted living facilities. Procedural compliance rates also were low. Proposed benchmarks for the number of times hand washing should occur by each employee for each sector of food service during each phase of operation are seven times per hour for assisted living, nine times per hour for childcare, 29 times per hour for restaurants, and 11 times per hour for schools. These benchmarks are high, especially for restaurant employees. Implementation would mean lost productivity and potential for dermatitis; thus, active managerial control over work assignments is needed. These benchmarks can be used for training and to guide employee hand washing behaviors.\",\n \"title\": \"Hand washing frequencies and procedures used in retail food services.\"\n },\n {\n \"docid\": \"MED-1638\",\n \"text\": \"OBJECTIVE: Migratory capacity of endothelial progenitor cells (EPCs) and mature endothelial cells (ECs) is a key prerequisite for endothelial repair after denuding injury or endothelial damage. METHODS AND RESULTS: We demonstrate that caffeine in physiologically relevant concentrations (50 to 100 micromol/L) induces migration of human EPCs as well as mature ECs. In patients with coronary artery disease (CAD), caffeinated coffee increased caffeine serum concentration from 2 micromol/L to 23 micromol/L, coinciding with a significant increase in migratory activity of patient-derived EPCs. Decaffeinated coffee neither affected caffeine serum levels nor migratory capacity of EPCs. Treatment with caffeine for 7 to 10 days in a mouse-model improved endothelial repair after denudation of the carotid artery. The enhancement of reendothelialization by caffeine was significantly reduced in AMPK knockout mice compared to wild-type animals. Transplantation of wild-type and AMPK(-/-) bone marrow into wild-type mice revealed no difference in caffeine challenged reendothelialization. ECs which were depleted of mitochondrial DNA did not migrate when challenged with caffeine, suggesting a potential role for mitochondria in caffeine-dependent migration. CONCLUSIONS: These results provide evidence that caffeine enhances endothelial cell migration and reendothelialization in part through an AMPK-dependent mechanism, suggesting a beneficial role for caffeine in endothelial repair.\",\n \"title\": \"Caffeine enhances endothelial repair by an AMPK-dependent mechanism.\"\n },\n {\n \"docid\": \"MED-2585\",\n \"text\": \"Inositol hexaphosphate (IP6) is a naturally occurring polyphosphorylated carbohydrate that is present in substantial amounts in almost all plant and mammalian cells. It was recently recognized to possess multiple biological functions. A striking anticancer effect of IP6 was demonstrated in different experimental models. Inositol is also a natural constituent possessing moderate anticancer activity. The most consistent and best anticancer results were obtained from the combination of IP6 plus inositol. In addition to reducing cell proliferation, IP6 increases differentiation of malignant cells, often resulting in a reversion to normal phenotype. Exogenously administered IP6 is rapidly taken into the cells and dephosphorylated to lower-phosphate inositol phosphates, which further interfere with signal transduction pathways and cell cycle arrest. Enhanced immunity and antioxidant properties can also contribute to tumor cell destruction. However, the molecular mechanisms underlying this anticancer action are not fully understood. Because it is abundantly present in regular diet, efficiently absorbed from the gastrointestinal tract, and safe, IP6 holds great promise in our strategies for the prevention and treatment of cancer. IP6 plus inositol enhances the anticancer effect of conventional chemotherapy, controls cancer metastases, and improves the quality of life, as shown in a pilot clinical trial. The data strongly argue for the use of IP6 plus inositol in our strategies for cancer prevention and treatment. However, the effectiveness and safety of IP6 plus inositol at therapeutic doses needs to be determined in phase I and phase II clinical trials in humans.\",\n \"title\": \"Cancer inhibition by inositol hexaphosphate (IP6) and inositol: from laboratory to clinic.\"\n },\n {\n \"docid\": \"MED-4226\",\n \"text\": \"Bone, as well as liver and lung, is one of the most preferential metastatic target sites for cancers including breast, prostate, and lung cancers and the consequences are always devastating. Like other metastasis, breast cancer bone metastasis consists of several steps from the escape of primary site to the colonization in target site. This review focuses on several key steps including: 1. Invasion and escape from primary tumor site. 2. Target migration toward bone. 3. Specific adhesion and arrest in bone. 4. Establishment of metastasis in bone. The factors involved in this process will provide good targets for therapy. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.\",\n \"title\": \"Mechanisms of breast cancer bone metastasis.\"\n },\n {\n \"docid\": \"MED-5120\",\n \"text\": \"Human gammadeltaT lymphocytes are a subset of T cells and are a first line of defense against microbes and tumors. These gammadeltaT cells can be primed by nitrogen-containing bisphosphonates, and certain short-chain alkylamines. These primed gammadeltaT cells have an enhanced capacity to proliferate and to secrete cytokines upon ex vivo exposure to a wide variety of microbes and tumor cells. The largest dietary source of alkylamines is L-theanine, an amino acid unique to tea beverages that is catabolized to ethylamine. Supplementation of subjects with capsules containing L-theanine and catechins has recently been shown to decrease the incidence of cold and flu symptoms, while enhancing gammadeltaT cell function.\",\n \"title\": \"L-theanine intervention enhances human gammadeltaT lymphocyte function.\"\n }\n]"}}},{"rowIdx":189,"cells":{"query_id":{"kind":"string","value":"10500"},"query":{"kind":"string","value":"How do government bond yields work?"},"positive_passages":{"kind":"list like","value":[{"docid":"189761","text":"Imagine a $1,000 face value bond paying 10% interest semi-annually. That means every 6 months there is $50 being paid. Now, if the price of that bond doubled to $2,000, what is the yield? It is still paying $50 every 6 months but now sports a 5% yield as the price went up a great deal. Similarly, if the price of the bond was cut in half to $500, now it is yielding 20% because it is still paying out the $50 every 6 months. The dollar figure is fixed. What percentage of the price it is can vary and that is why there is the inverse relationship between prices and yields. Note that the length of the bond isn't mentioned here where while usually longer bonds will have higher yields, there can be inverted yield curves as well as calls on some bonds. Also, inflation-indexed and convertible bonds could have different calculations used as principal adjustments or possible conversion to stock can change a perception on the overall return.","title":""},{"docid":"466315","text":"Why does the rising price of a bond pushes it's yield down? The bond price and its yield are linked; if one goes up, the other must go down. This is because the cash flows from the bond are fixed, predetermined. The market price of the bond fluctuates. Now what if people are suddenly willing to pay more for the same fixed payments? It must mean that the return, i.e. the yield, will be lower. Here we see that risk associated with the bonds in question has skyrocketed, and thus bonds' returns has skyrocketed, too. Am I right? The default risk has increased, yes. Now, I assume that bonds' price is determined by the market (issued by a state, traded at the market). Is that correct? Correct, as long as you are talking about the market price. Then who determines bonds' yields? I mean, isn't it fixed? Or - in the FT quote above - they are talking about the yields for the new bonds issued that particular month? The yield is not fixed - the cash flows are. Yield is the internal rate of return. See my answer above to your first question.","title":""}],"string":"[\n {\n \"docid\": \"189761\",\n \"text\": \"Imagine a $1,000 face value bond paying 10% interest semi-annually. That means every 6 months there is $50 being paid. Now, if the price of that bond doubled to $2,000, what is the yield? It is still paying $50 every 6 months but now sports a 5% yield as the price went up a great deal. Similarly, if the price of the bond was cut in half to $500, now it is yielding 20% because it is still paying out the $50 every 6 months. The dollar figure is fixed. What percentage of the price it is can vary and that is why there is the inverse relationship between prices and yields. Note that the length of the bond isn't mentioned here where while usually longer bonds will have higher yields, there can be inverted yield curves as well as calls on some bonds. Also, inflation-indexed and convertible bonds could have different calculations used as principal adjustments or possible conversion to stock can change a perception on the overall return.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"466315\",\n \"text\": \"Why does the rising price of a bond pushes it's yield down? The bond price and its yield are linked; if one goes up, the other must go down. This is because the cash flows from the bond are fixed, predetermined. The market price of the bond fluctuates. Now what if people are suddenly willing to pay more for the same fixed payments? It must mean that the return, i.e. the yield, will be lower. Here we see that risk associated with the bonds in question has skyrocketed, and thus bonds' returns has skyrocketed, too. Am I right? The default risk has increased, yes. Now, I assume that bonds' price is determined by the market (issued by a state, traded at the market). Is that correct? Correct, as long as you are talking about the market price. Then who determines bonds' yields? I mean, isn't it fixed? Or - in the FT quote above - they are talking about the yields for the new bonds issued that particular month? The yield is not fixed - the cash flows are. Yield is the internal rate of return. See my answer above to your first question.\",\n \"title\": \"\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"416513","text":"Yield is the term used to describe how much income the bond will generate if the bond was purchased at a particular moment in time. If I pay $100 for a one year, $100 par value bond that pays 5% interest then the bond yields 5% since I will receive $5 from a $100 investment if I held the bond to maturity. If I pay $90 for the same one year bond then the bond yields 17% since I will receive $15 from a $90 investment if I held the bond to maturity. There are many factors that affect what yield creditors will accept: It is the last bullet that ultimately determines yield. The other factors feed into the creditor’s desire to hold money today versus receiving money in the future. I desire money in my hand more than a promise to receive money in the future. In order to entice me to lend my money someone must offer me an incentive. Thus, they must offer me more money in the future in order for me to part with money I have. A yield curve is a snapshot of the yields for different loan durations. The x-axis is the amount of time left on the bond while the y-axis is the yield. The most cited yield curve is the US treasury curve which displays the yields for loans to the US government. The yield curve changes while bonds are being traded thus it is always a snapshot of a particular moment in time. Short term loans typically have less yield than longer term loans since there is less uncertainty about the near future. Yield curves will flatten or slightly invert when creditors desire to keep their money instead of loaning it out. This can occur because of a sudden disruption in the market that causes uncertainty about the future which leads to an increase in the demand for cash on hand. The US government yield curve should be looked at with some reservation however since there is a very large creditor to the US government that has the ability to loan the government an unlimited amount of funds.","title":""},{"docid":"127434","text":"You’ve really got three or four questions going here… and it’s clear that a gap in understanding one component of how bonds work (pricing) is having a ripple effect across the other facets of your question. The reality is that everybody’s answers so far touch on various pieces of your general question, but maybe I can help by integrating. So, let’s start by nailing down what your actual questions are: 1. Why do mortgage rates (tend to) increase when the published treasury bond rate increases? I’m going to come back to this, because it requires a lot of building blocks. 2. What’s the math behind a bond yield increasing (price falling?) This gets complicated, fast. Especially when you start talking about selling the bond in the middle of its time period. Many people that trade in bonds use financial calculators, Excel, or pre-calculated tables to simplify or even just approximate the value of a bond. But here’s a simple example that shows the math. Let’s say we’ve got a bond that is issued by… Dell for $10,000. The company will pay it back in 5 years, and it is offering an 8% rate. Interest payments will only be paid annually. Remember that the amount Dell has promised to pay in interest is fixed for the life of the bond, and is called the ‘coupon’ rate. We can think about the way the payouts will be paid in the following table: As I’m sure you know, the value of a bond (its yield) comes from two sources: the interest payments, and the return of the principal. But, if you as an investor paid $14,000 for this bond, you would usually be wrong. You need to ‘discount’ those amounts to take into account the ‘time value of money’. This is why when you are dealing in bonds it is important to know the ‘coupon rate’ (what is Dell paying each period?). But it is also important to know your sellers’/buyers’ own personal discount rates. This will vary from person to person and institution to institution, but it is what actually sets the PRICE you would buy this bond for. There are three general cases for the discount rate (or the MARKET rate). First, where the market rate == the coupon rate. This is known as “par” in bond parlance. Second, where the market rate < the coupon rate. This is known as “premium” in bond parlance. Third, where the market rate > coupon rate. This is known as a ‘discount’ bond. But before we get into those in too much depth, how does discounting work? The idea behind discounting is that you need to account for the idea that a dollar today is not worth the same as a dollar tomorrow. (It’s usually worth ‘more’ tomorrow.) You discount a lump sum, like the return of the principal, differently than you do a series of equal cash flows, like the stream of $800 interest payments. The formula for discounting a lump sum is: Present Value=Future Value* (1/(1+interest rate))^((# of periods)) The formula for discounting a stream of equal payments is: Present Value=(Single Payment)* (〖1-(1+i)〗^((-n))/i) (i = interest rate and n = number of periods) **cite investopedia So let’s look at how this would look in pricing the pretend Dell bond as a par bond. First, we discount the return of the $10,000 principal as (10,000 * (1 / 1.08)^5). That equals $6,807.82. Next we discount the 5 equal payments of $800 as (800* (3.9902)). I just plugged and chugged but you can do that yourself. That equals $3,192.18. You may get slightly different numbers with rounding. So you add the two together, and it says that you would be willing to pay ($6,807.82 + $3,192.18) = $10,000. Surprise! When the bond is a par bond you’re basically being compensated for the time value of money with the interest payments. You purchase the bond at the ‘face value’, which is the principal that will be returned at the end. If you worked through the math for a 6% discount rate on an 8% coupon bond, you would see that it’s “premium”, because you would pay more than the principal that is returned to obtain the bond [10,842.87 vs 10,000]. Similarly, if you work through the math for a 10% discount rate on an 8% coupon bond, it’s a ‘discount’ bond because you will pay less than the principal that is returned for the bond [9,241.84 vs 10,000]. It’s easy to see how an investor could hold our imaginary Dell bond for one year, collect the first interest payment, and then sell the bond on to another investor. The mechanics of the calculations are the same, except that one less interest payment is available, and the principal will be returned one year sooner… so N=4 in both formulae. Still with me? Now that we’re on the same page about how a bond is priced, we can talk about “Yield To Maturity”, which is at the heart of your main question. Bond “yields” like the ones you can access on CNBC or Yahoo!Finance or wherever you may be looking are actually taking the reverse approach to this. In these cases the prices are ‘fixed’ in that the sellers have listed the bonds for sale, and specified the price. Since the coupon values are fixed already by whatever organization issued the bond, the rate of return can be imputed from those values. To do that, you just do a bit of algebra and swap “present value” and “future value” in our two equations. Let’s say that Dell has gone private, had an awesome year, and figured out how to make robot unicorns that do wonderful things for all mankind. You decide that now would be a great time to sell your bond after holding it for one year… and collecting that $800 interest payment. You think you’d like to sell it for $10,500. (Since the principal return is fixed (+10,000); the number of periods is fixed (4); and the interest payments are fixed ($800); but you’ve changed the price... something else has to adjust and that is the discount rate.) It’s kind of tricky to actually use those equations to solve for this by hand… you end up with two equations… one unknown, and set them equal. So, the easiest way to solve for this rate is actually in Excel, using the function =RATE(NPER, PMT, PV, FV). NPER = 4, PMT = 800, PV=-10500, and FV=10000. Hint to make sure that you catch the minus sign in front of the present value… buyer pays now for the positive return of 10,000 in the future. That shows 6.54% as the effective discount rate (or rate of return) for the investor. That is the same thing as the yield to maturity. It specifies the return that a bond investor would see if he or she purchased the bond today and held it to maturity. 3. What factors (in terms of supply and demand) drive changes in the bond market? I hope it’s clear now how the tradeoff works between yields going UP when prices go DOWN, and vice versa. It happens because the COUPON rate, the number of periods, and the return of principal for a bond are fixed. So when someone sells a bond in the middle of its term, the only things that can change are the price and corresponding yield/discount rate. Other commenters… including you… have touched on some of the reasons why the prices go up and down. Generally speaking, it’s because of the basics of supply and demand… higher level of bonds for sale to be purchased by same level of demand will mean prices go down. But it’s not ‘just because interest rates are going up and down’. It has a lot more to do with the expectations for 1) risk, 2) return and 3) future inflation. Sometimes it is action by the Fed, as Joe Taxpayer has pointed out. If they sell a lot of bonds, then the basics of higher supply for a set level of demand imply that the prices should go down. Prices going down on a bond imply that yields will go up. (I really hope that’s clear by now). This is a common monetary lever that the government uses to ‘remove money’ from the system, in that they receive payments from an investor up front when the investor buys the bond from the Fed, and then the Fed gradually return that cash back into the system over time. Sometimes it is due to uncertainty about the future. If investors at large believe that inflation is coming, then bonds become a less attractive investment, as the dollars received for future payments will be less valuable. This could lead to a sell-off in the bond markets, because investors want to cash out their bonds and transfer that capital to something that will preserve their value under inflation. Here again an increase in supply of bonds for sale will lead to decreased prices and higher yields. At the end of the day it is really hard to predict exactly which direction bond markets will be moving, and more importantly WHY. If you figure it out, move to New York or Chicago or London and work as a trader in the bond markets. You’ll make a killing, and if you’d like I will be glad to drive your cars for you. 4. How does the availability of money supply for banks drive changes in other lending rates? When any investment organization forms, it builds its portfolio to try to deliver a set return at the lowest risk possible. As a corollary to that, it tries to deliver the maximum return possible for a given level of risk. When we’re talking about a bank, DumbCoder’s answer is dead on. Banks have various options to choose from, and a 10-year T-bond is broadly seen as one of the least risky investments. Thus, it is a benchmark for other investments. 5. So… now, why do mortgage rates tend to increase when the published treasury bond yield rate increases? The traditional, residential 30-year mortgage is VERY similar to a bond investment. There is a long-term investment horizon, with fixed cash payments over the term of the note. But the principal is returned incrementally during the life of the loan. So, since mortgages are ‘more risky’ than the 10-year treasury bond, they will carry a certain premium that is tied to how much more risky an individual is as a borrower than the US government. And here it is… no one actually directly changes the interest rate on 10-year treasuries. Not even the Fed. The Fed sets a price constraint that it will sell bonds at during its periodic auctions. Buyers bid for those, and the resulting prices imply the yield rate. If the yield rate for current 10-year bonds increases, then banks take it as a sign that everyone in the investment community sees some sign of increased risk in the future. This might be from inflation. This might be from uncertain economic performance. But whatever it is, they operate with some rule of thumb that their 30-year mortgage rate for excellent credit borrowers will be the 10-year plus 1.5% or something. And they publish their rates.","title":""},{"docid":"231268","text":"Companies do not support their stock. Once the security is out on the wild (market), its price fluctuates according to what investors think they are worth. Support is a whole different concept, financially speaking: Support or support level refers to the price level below which, historically, a stock has had difficulty falling. It is the level at which buyers tend to enter the stock. So it is the lowest assumed price for that stock. Once it reaches its price, buyers will rush to the stock, raising its price. The company wants to keep the stock price at acceptable levels, as it can be seen as the general view of the company's health. Also several employees/executives in the company have stock or stock options, so it is in their interest to keep their stock price up. A bond that goes down in value may indicate a believe the bond issuer (government in this case) won't honor the bond when it matures. As for bonds, there is a wealth of reading in this site: Can someone explain how government bonds work? Who sets the prices on government bonds? Basic understanding of bonds, values, rates and yields","title":""},{"docid":"285176","text":"The assumption that bonds have been issued with a negative coupon is not correct, or at least is has not occurred thus far. We'll look at this future possibility in the final paragraph. For now, lets look at the current bond market. The issuance of government bonds which carry a negative gross redemption yield is the result of governments issuing bonds at an issue price which exceed the nominal/redemption price and any coupon yield receivable over the life of the bond. I can find no instances of bonds with a negative coupon, though many have tiny positive coupon yields. The short seller of a bond with a negative gross redemption yield will be liable to pay the buyer the interest amount determined by the coupon. If the short seller has borrowed the bonds in order to sell them, then the short seller will receive the interest due from the lender to offset the interest paid to the buyer. If the short seller has not borrowed the bonds, but has sold them using some sort of synthetic contract such as a Contract for Difference, then the short seller will pay the coupon without receiving any offsetting payment. I thought this was an interesting question and it will be interesting to see if, at some time in the future, governments do ever issue bonds with a negative coupon. To date, this does not appear to have happened. So what would happen if we assume that a government issues a bond with a negative coupon. The buyer of the bond would be required to pay the equivalent yield to the government according to the bond contract specification. If an investor sells short such a bond, they would then become entitled to receive the interest from the buyer. If they have borrowed the bonds in order to sell them short, then they would pay any interest received back to the lender - this chain should eventually end with the ultimate owner/lender paying the government their dues. If they have sold short using a synthetic contract, then presumably they would keep the interest from themselves.","title":""},{"docid":"388391","text":"\"So \"\"Operation Twist\"\" is actually a pretty simple concept. Here's the break down: The Fed sells short-term treasury bonds that it already holds on its books. Short-term treasury bonds refer to - bonds that mature in less than three years. Then: Uses that money to buy long term treasury bonds. Long-term treasury bonds refer to - bonds that mature in six to 30 years The reason: The fed buys these longer-term treasuries to lower longer-term interest rates and encourage more borrowing and spending. Diving deeper into how it works: So the Fed can easily determine short-term rates by using the Federal funds rate this rate has a direct effect on the following: However this does not play a direct role in influencing the rate of long-term loans (what you might pay on a 30-year fixed mortgage). Instead, long-term rates are determined by investors who buy and sell bonds in the bond market, which changes daily. These bond yields fluctuate depending on the health of the economy and inflation. However, the Fed funds rate does play an indirect role in these rates. So now that we know a little more about what effects what rate, why does lower long-term rates in treasuries influence my 30yr fixed mortgage? Well when you are looking for a loan you are entering a market and competing against other people, by people I mean anyone looking for money (e.g: my grandmother, companies, or the US government). The bank that lends you money has to decide weather the deal you are offering them is better then another deal on the market. If the risk of lending to one person is the same as the risk of lending to another, the bank will make whichever loan yields the higher interest rate. The U.S. government is considered a very safe borrower, so much so that government bonds are considered almost “risk free”, but because of the lower risk the rate of return is lower. So now the bank has to factor in this risk and make its decision weather to lend you money, or the government. So, if the government were to go to the market and buy its own long-term bonds it is adding demand in the market causing the price of the bond to rise in effect lowering the interest rate (when price goes up, yield goes down). So when you go back and ask for a loan it has to re-evaluate and decide \"\"Is it worth giving this money to Joe McFreeBeer instead and collecting a higher yield?\"\" (After all, Joe McFreeBeer is a nice guy). Here's an example: Lets say the US has a rating of 10 out of 10 and its bonds pay a 2% yield. Now lets say for each lower mark in rating the bank will lend at a minimum of 1% higher and your rating is 8 of 10. So if you go to market, the lowest rate you can get will be 4%. Now lets say price rises on the US treasury and causes the rate to go down by 1%. In this scenario you will now be able to get a loan for 3% and someone with a rating of 7 of 10 would be able to get that 4% loan. Here's some more info and explinations: Why is the Government Buying Long-Term Bonds? What Is 'Operation Twist'? A Q&A on US Fed Program Federal Reserve for Beginners Federal Open Market Committee\"","title":""},{"docid":"144177","text":"\"If you owned a bank how would you invest the bank's money? Typically banks are involved in loaning out money to businesses, people, and government at a higher interest rate then what they are paying to depositors. This is the spread and how they make money. If the bank determines that the yields on government bonds is more attractive then loaning the money out to businesses and people then the bank will purchase government bonds. It can also decide the other way. In this manner the mortgage and bond markets are always competing for capital and tend to offer very similar yields. Certain banks have the unique privilege of being able to borrow money from the FED at the Federal Funds rate and use this money to purchase government debt or loan it out to other banks or purchase other debt products. In this manner you see a high correlation between the FED funds rate, mortgage rates, and treasury yields. Other political factors include legislation that encourages mortgage lending (see Community Reinvestment Act) where banks may not have made the loans without said legislation. In short, keep your eye on the FED and ask yourself: \"\"Does the FED want rates to rise?\"\" and \"\"Can the US government afford rising rates?\"\" The answer to these two questions is no. However, the FED may be pressured to \"\"stop the presses\"\" if inflation becomes unwieldy and the FED actually starts to care about food and energy prices. So far this hasn't been the case.\"","title":""},{"docid":"446214","text":"\"What is a bond price? A bond is an asset, and like any tradeable asset it has a price. If I hold $10K face value of a certain GM bond, then I would be willing to sell it at some price, which may be more or less than $10K. Whoever is willing to sell it for the lowest amount determines the price. The price is determined by the market, just as all prices are. It's what you can sell a bond for. Bond prices may be quoted in various funny ways, like as a discount or premium relative to the face value or as a premium over a treasury, but at the end it all should be converted to how much you have to pay today. In this case, it's how much you would pay today to get a set of future coupon and principal payments. What is Yield to Maturity? A bond is a contract entitling you to a certain set of predefined cash flows. If you take that set of cash flows and discount them using a single rate at all maturities such that the discounted value is equal to the price, the single rate you have identified is the YTM. Mathematically, this is the same as finding the IRR (internal rate of return) of some set of cash flows. In this case the cash flows are the coupons and principal repayment. Other bond concepts. Note that the other aspects of a bond, like maturity, coupon rate, and face value, are immutably written into the bond contract. All they do is define what payments the bond entitles the owner to. They don't say how much someone would pay today in order to be entitled to those payments. One can't know how much a future payment is worth without discounting. If you know the appropriate discount rate at every relevant maturity, you could calculate the fair price of a bond. That's the other direction. YTM looks at the market price and associated cash flows and imputes what single discount rate would make that price fair. What is YTM good for? Recall what I said about IRR above. Why would anyone want to know what discount rate equates the cash flows of a project to its cost? Because it's an easy way to summarize how profitable the project is expected to be. YTM is a quick way to summarize the yield one would get on a bond if they were to buy it today and hold to maturity. If one bond has a higher YTM than another, than heuristically we believe it pays out more and should be associated with greater risk if the market is working properly. It can be used to compare bonds or to look at how changes in bond prices are affecting expected yields. Ask yourself, how would you compare two different bonds with different maturities and coupon rates? Which one is riskier or more profitable? The simplest way to summarize this information is with the yield to maturity. YTM is used frequently enough that when you just say a bond's \"\"yield,\"\" people will assume you are talking about its yield to maturity. What is YTM not good for? One thing to be wary of is using YTM as a discount rate. It looks like a discount rate but it works for that bond and that bond only. In reality each individual coupon payment has a true discount rate, and the discount rate at each horizon is different from each other horizon. Those are true discount rates that can be applied to any cash flow of similar risk to get the right price. We can think of YTM as some kind of average of those discount rates that produces the correct price for that bond only. You should never use it for discounting something else.\"","title":""},{"docid":"342485","text":"just pick a good bond and invest all your money there (since they're fairly low risk) No. That is basically throwing away your money and why would you do that. And who told you they are low risk. That is a very wrong premise. What factors should I consider in picking a bond and how would they weigh against each other? Quite a number of them to say, assuming these aren't government bonds(US, UK etc) How safe is the institution issuing the bond. Their income, business they are in, their past performance business wise and the bonds issued by them, if any. Check for the bond ratings issued by the rating agencies. Read the prospectus and check for any specific conditions i.e. bonds are callable, bonds can be retired under certain conditions, what happens if they default and what order will you be reimbursed(senior debt take priority). Where are interest rates heading, which will decide the price you are paying for the bond. And also the yield you will derive from the bond. How do you intend to invest the income, coupon, you will derive from the bonds. What is your time horizon to invest in bonds and similarly the bond's life. I have invested in stocks previously but realized that it isn't for me Bonds are much more difficult than equities. Stick to government bonds if you can, but they don't generate much income, considering the low interest rates environment. Now that QE is over you might expect interest rates to rise, but you can only wait. Or go for bonds from stable companies i.e. GE, Walmart. And no I am not saying you buy their bonds in any imaginable way.","title":""},{"docid":"395111","text":"The 10yr bond pays coupons semi annually. The yield % is what you would get annually if you hold the bond to full term. The coupon payment won't be exactly 1.65%/2 because of how bond pricing and yields work. The yield commonly quoted does not tell you how much each interest payment is. You have to look at the price and coupon of a specific individual bond. The rate you see is the market equilibrium yield at the present. Example, I offer two different people two different bonds. Joe buys a 10yr bond paying 5% coupons semi annually at a par value of $1000. I charge him $1000. Bob wants to buy a 10yr bond paying 10% coupons semi annually at a par value of $1000. I charge him $1500 for this. The yield is similar between the two (not equal due to math details but lets assume). So at the end of 10 yrs, the two have roughly the same total amount of $. Bob's paid more each year but he paid more up front. This is why the federal govt can issue bonds with diff coupons and the market prices them so the yield rises/falls to the market clearing yield.","title":""},{"docid":"498645","text":"\"Bonds might not be simple, but in general there are only a few variables that need to be understood: bid, coupon (interest) rate, maturity, and yield. Bond tables clearly lay those out, and if you're talking about government bonds a lot of things (like convertibles) don't apply (although default is still a concern). This might be overly simplistic, but I view ETF's primarily as an easy way to bring somewhat esoteric instruments (like grain futures) into the easily available markets of Nasdaq and the NYSE. That they got \"\"enhanced\"\" with leveraged funds and the such is interesting, but perhaps not the original intent of the instrument. Complicating your situation a bit more is the fee that gets tacked onto the ETF. Even Vanguard government bond funds hang out north of 0.1%. That's not huge, but it's not particularly appealing either considering that (unlike rounding up live cattle futures), it's not that much work to buy US government bonds, so the expense might not seem worth it to someone who's comfortable purchasing the securities directly. I'd be interested to see someone else's view on this, but in general I'd say that if you know what you want and know how to buy it, the government bond ETF becomes a lot less relevant as the liquidity offered (including the actual \"\"ease of transacting\"\") seem to to be the biggest factors in favor. From Investopedia's description: The bond ETF is an exciting new addition to the bond market, offering an excellent alternative to self-directed investors who, looking for ease of trading and increased price transparency, want to practice indexing or active bond trading. However, bond ETFs are suitable for particular strategies. If, for instance, you are looking to create a specific income stream, bond ETFs may not be for you. Be sure to compare your alternatives before investing.\"","title":""},{"docid":"260984","text":"There are a few other factors possible here: Taxes - Something you don't mention is what are the tax rates on each of those choices. If the 4% gain is taxed at 33% while the 3% government bond is taxed at 0% then it may well make more sense to have the government bond that makes more money after taxes. Potential changes in rates - Could that 4% rate change at any time? Yield curves are an idea here to consider where at times they can become inverted where short-term bonds yield more than long-term bonds due to expectations about rates. Some banks may advertise a special rate for a limited time to try to get more deposits and then change the rate later. Beware the fine print. Could the bond have some kind of extra feature on it? For example, in the US there are bonds known as TIPS that while the interest rate may be low, there is a principal adjustment that comes as part of the inflation adjustment that is part how the security is structured.","title":""},{"docid":"411966","text":"\"The most fundamental observation of bond pricing is this: Bond price is inversely proportional to bond yields When bond yields rise, the price of the bond falls. When bond yields fall, the price of the bond rises. Higher rates are \"\"bad\"\" for bonds. If a selloff occurs in the Russian government bond space (i.e. prices are going down), the yield on that bond is going to increase as a consequence.\"","title":""},{"docid":"538898","text":"The Fed sets the overnight borrowing costs by setting its overnight target rate. The markets determine the rates at which the treasury can borrow through the issuance of bonds. The Fed's actions will certainly influence the price of very short term bonds, but the Fed's influence on anything other than very short term bonds in the current environment is very muted. Currently, the most influential factor keeping bond prices high and yields low is the high demand for US treasuries coming from overseas governments and institutions. This is being caused by two factors : sluggish growth in overseas economies and the ongoing strength of the US dollar. With many European government bonds offering negative redemption yields, income investors see US yields as relatively attractive. Those non-US economies which do not have negative bond yields either have near zero yields or large currency risks or both. Political issues such as the survival of the Euro also weigh heavily on market perceptions of the current attractiveness of the US dollar. Italian banks may be about to deliver a shock to the Eurozone, and the Spanish and French banks may not be far behind. Another factor is the continued threat of deflation. Growth is slowing around the world which negatively effects demand. Commodity prices remain depressed. Low growth and recession outside of the US translate into a prolonged period of near zero interest rates elsewhere together with renewed QE programmes in Europe, Japan, and possibly elsewhere. This makes the US look relatively attractive and so there is huge demand for US dollars and bonds. Any significant move in US interest rates risks driving to dollar ever higher which would be very negative for the future earning of US companies which rely on exports and foreign income. All of this makes the market believe that the Fed's hands are tied and low bond yields are here for the foreseeable future. Of course, even in the US growth is relatively slow and vulnerable to a loss of steam following a move in interest rates.","title":""},{"docid":"587032","text":"\"The simple answer is that, even though mortgages can go for 10, 15, 20 and 30 year terms in the U.S., they're typically backed by bonds sold to investors that mature in 10 years, which is the standard term for most bonds. These bonds, in the open market, are compared by investors with the 10-year Treasury note, which is the gold standard for low-risk investment; the U.S. Government has a solid history of always paying its bills (though this reputation is being tested in recent years with fights over the debt ceiling and government budgets). The savvy investor, therefore, knows that he or she can make at least the yield from the 10-year T-note in that time frame, with virtually zero risk. Anything else on the market is seen as being a higher risk, and so investors demand higher yields (by making lower bids, forcing the issuer to issue more bonds to get the money it needs up front). Mortgage-backed securities are usually in the next tier above T-debt in terms of risk; when backed by prime-rate mortgages they're typically AAA-rated, making them available to \"\"institutional investors\"\" like banks, mutual funds, etc. This forms a balancing act; mortgage-backed securities issuers typically can't get the yield of a T-note, because no matter how low their risk, T-debt is lower (because one bank doesn't have the power to tax the entire U.S. population). But, they're almost as good because they're still very stable, low-risk debt. This bond price, and the resulting yield, is in turn the baseline for a long-term loan by the bank to an individual. The bank, watching the market and its other bond packages, knows what it can get for a package of bonds backed by your mortgage (and others with similar credit scores). It will therefore take this number, add a couple of percentage points to make some money for itself and its stockholders (how much the bank can add is tacitly controlled by other market forces; you're allowed to shop around for the lowest rate you can get, which limits any one bank's ability to jack up rates), and this is the rate you see advertised and - hopefully - what shows up on your paperwork after you apply.\"","title":""},{"docid":"495600","text":"\"Question 1: How do I start? or \"\"the broker\"\" problem Get an online broker. You can do a wire transfer to fund the account from your bank. Question 2: What criticism do you have for my plan? Dividend investing is smart. The only problem is that everyone's currently doing it. There is an insatiable demand for yield, not just individual investors but investment firms and pension funds that need to generate income to fund retirements for their clients. As more investors purchase the shares of dividend paying securities, the share price goes up. As the share price goes up, the dividend yield goes down. Same for bonds. For example, if a stock pays $1 per year in dividends, and you purchase the shares at $20/each, then your yearly return (not including share price fluctuations) would be 1/20 = 5%. But if you end up having to pay $30 per share, then your yearly return would be 1/30 or 3.3% yield. The more money you invest, the bigger this difference becomes; with $100K invested you'd make about $1.6K more at 5%. (BTW, don't put all your money in any small group of stocks, you want to diversify). ETFs work the same way, where new investors buying the shares cause the custodian to purchase more shares of the underlying securities, thus driving up the price up and yield down. Instead of ETFs, I'd have a look at something called closed end funds, or CEFs which also hold an underlying basket of securities but often trade at a discount to their net asset value, unlike ETFs. CEFs usually have higher yields than their ETF counterparts. I can't fully describe the ins and outs here in this space, but you'll definately want to do some research on them to better understand what you're buying, and HOW to successfully buy (ie make sure you're buying at a historically steep discount to NAV [https://seekingalpha.com/article/1116411-the-closed-end-fund-trifecta-how-to-analyze-a-cef] and where to screen [https://www.cefconnect.com/closed-end-funds-screener] Regardless of whether you decide to buy stocks, bonds, ETFs, CEFs, sell puts, or some mix, the best advice I can give is to a) diversify (personally, with a single RARE exception, I never let any one holding account for more than 2% of my total portfolio value), and b) space out your purchases over time. b) is important because we've been in a low interest rate environment since about 2009, and when the risk free rate of return is very low, investors purchase stocks and bonds which results in lower yields. As the risk free rate of return is expected to finally start slowly rising in 2017 and gradually over time, there should be gradual downward pressure (ie selling) on the prices of dividend stocks and especially bonds meaning you'll get better yields if you wait. Then again, we could hit a recession and the central banks actually lower rates which is why I say you want to space your purchases out.\"","title":""},{"docid":"239271","text":"Big money, by vitue of its own existence, produces value. What's a person to do with it? Stuff it under a mattress and earn 0 yield? No. If you want safety, you'll put it in AAA rated US gov't bonds and help fund the government. If you want yield, you'll put it in broadly diversified equities investments, small companies, big companies, energy companies, tech companies, media companies, and so on, and soak up the net gain while injecting much needed capital investment directly into those industries, financing start up costs like construction and equipment procurement costs, as well as staffing costs. Yes, big money absolutely creates value. The trains, cars, roads, and sidewalks you travel through to get to work? All financed by filthy rich people money. The building you work in and the equipment you use? Likely financed by filthy rich people money as well. Its called financial intermediation and capital arbitrage, and you can thank your Gods you live in a country where the government allows it to operate efficiently.","title":""},{"docid":"215189","text":"\"All of the other answers here are accurate, but (I think) are missing the point as to the question, which rests on how Bonds work in the first place. The bond specifies a payback AMOUNT and DATE. Let's say it is $10,000 and one year from today. If you buy that today for $9900, your yield will be 1%. If you buy it today for $11,000, your yield will be less than 0% (please don't make me do the math - it's just under negative 1%). You might be willing to pay that 1% (rather than receive 1%) for the certainty that you will definitely get your money back. The combined actions of all the people who may be willing to pay a little more or a little less for the safety of a US Treasury Bond is what people call \"\"the Market.\"\" Market forces (generally, investor confidence) will drive the price up and down, which affects the yield. All the other stuff - coupons and inflation and whatnot - all of that only makes sense if you understand that you aren't buying a rate of return, you are buying a payback amount and date.\"","title":""},{"docid":"97729","text":"You can look at TIPS (which have some inflation protection built in). Generally short term bonds are better than long if you expect rates to rise soon. Other ways that you can protect yourself are to choose higher yield corporate bonds instead of government bonds, or to use foreign bonds. There are plenty of bond funds like Templeton Global or ETFs that offer such features. Find one that will work for you.","title":""},{"docid":"227433","text":"\"Why does the yield go up if the country is economically unstable? The yield will rise when instability increases because the risk of default increases. If the case of Greece, the instability of government finances resulted in a 50% \"\"haircut\"\" for bond holders in 2011. In other words, bond holders suffered a 50% write down in the nominal value of their bonds. This means that holding these bonds until maturity will mean they will only receive half of the original nominal value of the bond, and that is assuming no further write downs occur. Why does selling a bond drive up the yield? Significant selling of bonds means that sellers are worried about future prospects. Sellers will outnumber buyers, so sellers will have to reduce their offer price in order to attract new buyers. So if you think Greece is not going to default as it's highly likely a country would completely default, wouldn't it make sense to hold onto the bonds? If you think that it is highly unlikely that Greece will default and the prices and yields are attractive, then Greek bonds may look like an attractive investment. However, keep in mind the fate of bond holders in 2011. They were attracted to Greek bonds by the price and yield, but they suffered a 50% haircut.\"","title":""},{"docid":"269550","text":"Buy a fund of bonds, there are plenty and are registered on your stockbroker account as 'funds' rather than shares. Otherwise, to the individual investor, they can be considered as the same thing. Funds (of bonds, rather than funds that contain property or shares or other investments) are often high yield, low volatility. You buy the fund, and let the manager work it for you. He buys bonds in accordance to the specification of the fund (ie some funds will say 'European only', or 'global high yield' etc) and he will buy and sell the bonds regularly. You never hold to maturity as this is handled for you - in many cases, the manager will be buying and selling bonds all the time in order to give you a stable fund that returns you a dividend. Private investors can buy bonds directly, but its not common. Should you do it? Up to you. Bonds return, the company issuing a corporate bond will do so at a fixed price with a fixed yield. At the end of the term, they return the principal. So a 20-year bond with a 5% yield will return someone who invests £10k, £500 a year and at the end of the 20 years will return the £10k. The corporate doesn't care who holds the bond, so you can happily sell it to someone else, probably for £10km give or take. People say to invest in bonds because they do not move much in value. In financially difficult times, this means bonds are more attractive to investors as they are a safe place to hold money while stocks drop, but in good times the opposite applies, no-one wants a fund returning 5% when they think they can get 20% growth from a stock.","title":""},{"docid":"457122","text":"\"For a two year time frame, a good insured savings account or a low-cost short-term government bond fund is most likely the way I would go. Depending on the specific amount, it may also be reasonable to look into directly buying government bonds. The reason for this is simply that in such a short time period, the stock market can be extremely volatile. Imagine if you had gone all in with the money on the stock market in, say, 2007, intending to withdraw the money after two years. Take a broad stock market index of your choice and see how much you'd have got back, and consider if you'd have felt comfortable sticking to your plan for the duration. Since you would likely be focused more on preservation of capital than returns during such a relatively short period, the risk of the stock market making a major (or even relatively minor) downturn in the interim would (should) be a bigger consideration than the possibility of a higher return. The \"\"return of capital, not return on capital\"\" rule. If the stock market falls by 10%, it must go up by 11% to break even. If it falls by 25%, it must go up by 33% to break even. If you are looking at a slightly longer time period, such as the example five years, then you might want to add some stocks to the mix for the possibility of a higher return. Still, however, since you have a specific goal in mind that is still reasonably close in time, I would likely keep a large fraction of the money in interest-bearing holdings (bank account, bonds, bond funds) rather than in the stock market. A good compromise may be medium-to-high-yield corporate bonds. It shouldn't be too difficult to find such bond funds that can return a few percentage points above risk-free interest, if you can live with the price volatility. Over time and as you get closer to actually needing the money, shift the holdings to lower-risk holdings to secure the capital amount. Yes, short-term government bonds tend to have dismal returns, particularly currently. (It's pretty much either that, or the country is just about bankrupt already, which means that the risk of default is quite high which is reflected in the interest premiums demanded by investors.) But the risk in most countries' short-term government bonds is also very much limited. And generally, when you are looking at using the money for a specific purpose within a defined (and relatively short) time frame, you want to reduce risk, even if that comes with the price tag of a slightly lower return. And, as always, never put all your eggs in one basket. A combination of government bonds from various countries may be appropriate, just as you should diversify between different stocks in a well-balanced portfolio. Make sure to check the limits on how much money is insured in a single account, for a single individual, in a single institution and for a household - you don't want to chase high interest bank accounts only to be burned by something like that if the institution goes bankrupt. Generally, the sooner you expect to need the money, the less risk you should take, even if that means a lower return on capital. And the risk progression (ignoring currency effects, which affects all of these equally) is roughly short-term government bonds, long-term government bonds or regular corporate bonds, high-yield corporate bonds, stock market large cap, stock market mid and low cap. Yes, there are exceptions, but that's a resonable rule of thumb.\"","title":""},{"docid":"462668","text":"\"This is a hard question to answer. Government debt and mortgages are loosely related. Banks typically use yields on government bonds to determine mortgage interest rates. The banks must be able to get higher rates from the mortgage otherwise they would buy government bonds. Your question mentions default so I'm assuming a country has reneged on its promise to pay either the principal or interest on government bonds. The main thing to consider is \"\"Who does not get their money?\"\". In other words, who does the government decide not to pay. This is the important part. The government will have some money so they could pay some bond holders. They must decide who to shaft. For example, let's look at who holds Greek government debt. Around 70% of Greek government debt is held outside Greece. See table below. The Greek government could decide to default only on the debt to foreign holders. In that case the banks in France and Switzerland would take the loss on their bonds. This could cause severe problems in France and Switzerland depending on the percentage of Greek bonds that make up the banks' assets. Greek banks would still face losses, however, since the price of their Greek bond holdings would drop sharply when the government defaults. Interestingly, the losses for the Greek banks may be smaller than the losses faced by the French and Swiss banks. This is usually the favored option chosen by government since the French and Swiss don't vote in Greece. Yields on Greek government bonds would rise dramatically. If your Greek mortgage is an adjustable rate mortgage then you could see some big adjustments upward. If you live in France or Switzerland then the bank that owns your mortgage may go under if Greece defaults. During liquidation the bank will sell their assets which includes mortgages and you will probably not notice any difference in your mortgage. As I stated earlier: this is a hard question to answer since the two financial instruments involved (bonds and mortgages) are similar but may or may not be related.\"","title":""},{"docid":"237317","text":"A large number of bond holders decide to sell their bonds. If they all decide to do this at the same time then there will be a large supply of bonds being sold in the market. This will drive down the price of the bonds which will increase yields. Why do bond yields move inversely to bond prices? You purchase a $100 bond today that yields 5%. You spent $100. The very next day the same bonds are being sold with a yield of 10%. If you wanted to sell your bond to someone you would have to sell it so it competed with the new bonds being sold. You could not sell it for $100 which is what you paid for it. You would have to sell it for less than the $100 you paid for it in order for it to have the equivalent yield of the new bonds being sold with a 10% yield. This is why bond yields move inversely to bond prices. Why does rising yields increase the cost of borrowing? If someone is trying to sell new bonds they will have to sell bonds that compete with the yields of the current bonds already in the market. If yields are rising on the existing bonds then the issuer of the new bonds will have to pay higher interest rates to offer equivalent yields on the new bonds. The issuer is now paying more in interest making it more expensive to borrow money. What are the incentives for the bond vigilante to sell his/her bonds? One reason a bond holder will sell his/her bonds is they believe inflation will outpace the yield on the bond they are holding. If a bond yields 3% and inflation is at 5% then the bond holder is essentially losing purchasing power if they continue to hold onto the bond. Another reason to sell would be if the bond holder has doubts in the ability of the issuer to repay the interest and/or principal of the bond.","title":""},{"docid":"131380","text":"Theoretically the yield curve is an expectation of inflation, however in practice (currently) the government yield curve is an expectation of banking fear. As you put your money with the government if you think the bank is going to default. With the FED lowering the longer end and making government less attractive, operation twist should theoretically lower both long term corp bond rates and stop people from buying long gov bonds (crowding out of capital).","title":""},{"docid":"523140","text":"G spread - you have a 5.5 year bond, you take your yield minus the yield on the 5.5y point (interpolated) of the benchmark sovereign curve. Think of G = Government. I Spread - same as G Spread but you use the relevant Swap Curve. E.g. USD bond, compare against the USD Swaps curve. I = interpolated. Z Spread - stands for zero volatility curve spread. You strip the swaps curve to get zero rates (i.e. Zero coupon rates for each tenor), then find the constant spread on top of each part of the curve's zero rates to arrive at your bond's yield. In G and I Spread, you're basically discounting the bond's cash flows using one rate (i.e. The interpolated yield on the curve). With Z Spread, you're discounting using the entire portion of the curve that's relevant to your bond's maturity.","title":""},{"docid":"370121","text":"I'm going to make an educated guess on #1. Money markets invest in bonds with a very short time to maturity. An MMA at a bank will be invested in government bonds. Yields on these bonds are really low right now. Thus the yield on that MMA is going to be pretty low. When you make a deposit in a savings account, the bank uses some of that money to lend back out to its customers in the form of car loans, mortgages, etc. These rates are higher, so the bank is willing to pay you a bit more than the yield MMA so they can use your money for these loans. For #2, your time window is short, so there aren't really a lot of options for you. Keeping your money where it is will actually cost you money in fees. You can do as I suggested in my comment above: close the current savings account that's hitting you with fees and open a (free) high yield savings account. You might get 1.1%. If you average $60k in the account over the next 6 months you'll earn $200-250 after taxes. You didn't ask about CDs, but lately shorter term CDs are paying less than savings accounts. Going out to a year will get you just above the rate on a high yield savings account; two years just a little more. These are outside your goal window, so they aren't an option for you.","title":""},{"docid":"4180","text":"\"I don't understand the worker mentality of accepting to be part of pension plans. The downside risk to you is ridiculously high -- you're basically making an investment that the next 30 years of corporate management and the company as a whole are going to be good. Pension plans are among the first to go.. employees that retired 20-30 years ago add no current value to the company, unless you consider that current employees are motivated by the idea of a pension or working for a company that \"\"takes care\"\" of its employees. Also, part of the reason pension funds are blowing up is that the risk-free return rate is less than 1%. I don't know who to blame or thank for that, but with government bonds now trading at negative yields in real and sometimes even absolute terms (see: Swiss yields), what else are you supposed to do?\"","title":""},{"docid":"462697","text":"\"that would imply that a 30Y US Treasury bond only yields 2.78%, which is nonsensically low. Those are annualized yields. It would be more precise to say that \"\"a 30Y US Treasury bond yields 2.78% per year (annualized) over 30 years\"\", but that terminology is implied in bond markets. So if you invest $1,000 in a 30-year T-bond, you will earn roughly 2.78% in interest per year. Also note that yield is calculated as if it compounded, meaning that investing in a 30-year T-bind will give you a return that is equivalent to putting it in a savings account that earns 1.39% interest (half of 2.78%) every 6 months and compounds, meaning you earn interest on top of interest. The trade-off for these low yields is you have virtually no default risk. Unlike a company that could go bankrupt and not pay back the bond, the US Government is virtually certain to pay off these bonds because it can print or borrow more money to pay off the debts. In addition, bonds in general (and especially treasuries) have very low market risk, meaning that their value fluctuates much less that equities, even indicies. S&P 500 indices may move anywhere between -40% and 50% in any given year, while T-bonds' range of movement is much lower, between -10% and 30% historically).\"","title":""},{"docid":"175819","text":"Your question asked about a specific time the yield curve flattened or inverted. There are other times when the yield curve inverted or flattened. You also imply in your question that investors were flocking to long term bonds which lowered their yields. I don't believe this is the case. I believe investors were fleeing from short term bonds causing the yields on short term bonds to rise to meet those of long term bonds. The chart below shows the history of yields on US bonds over time. The shaded areas are where the yield curve flattened or inverted. Notice that after 1982 it is the short term yields that rise sharply to meet or cross the yields on longer term bonds. The yields on longer term bonds move little compared to the movement in yields on the short term bonds. Thus it is investors moving out of short term bonds that cause the yield curve to flatten or invert. These investors are not moving into longer term bonds since the yields on the longer term bonds do not move much at all at these times. In fact, in 2006 the longer term bond market was only 25% of the total US public debt while short term bonds made up 75%. It would take less money to move the yields on longer term bonds than it would on short term bonds yet the longer term yields did not move near as much as short term yields. So why are investors or banks moving out of short term bonds causing their yields to rise? I believe this happens for one of two reasons: they are moving into higher yielding investments or they need to raise cash to cover bad investments. Charts and more information here.","title":""},{"docid":"136515","text":"\"Bonds still definitely have a place in many passive portfolios. While it is true that interest rates have been unusually low, yields on reasonable passive bond exposures are still around 2-4%. This is significantly better than both recent past inflation and expected inflation both of which are near zero. This is reasonable if not great return, but Bonds continue to have other nice properties like relatively low risk and diversification of stock portfolios (the \"\"offset[ing] losses\"\" you mention in the OP). So to say that bonds are \"\"no longer a good idea\"\" is certainly not correct. One could say bonds may no longer be a good idea for some people that have a particularly high risk tolerance and very high return requirements. However, to some extent, that has always been true. It is worth remembering also that there is some compelling evidence that global growth is starting to broadly slow down and many people believe that future stock returns and, in general, returns on all investments will be lower. This is much much harder to estimate than bond returns though. Depending on who you believe, bond returns may actually look relatively better than the have in the past. Edit in response to comment: Corporate bond correlation with stocks is positive but generally not very strong (except for high-yield junk bonds) so while they don't offset stock volatility (negative correlation) they do help diversify a stock portfolio. Government bonds have essentially zero correlation so they don't really offset volatility as much as just not add any. Negative correlation assets are generally called insurance and you tend to have to pay for them. So there is no free lunch here. Assets that reduce risk cost money, assets that add little risk give less return and assets that are more risky tend to give more return in the long run but you can feel the pain. The mix that is right for you depends on a lot of things, but for many people that mix involves some corporate and government bonds.\"","title":""}],"string":"[\n {\n \"docid\": \"416513\",\n \"text\": \"Yield is the term used to describe how much income the bond will generate if the bond was purchased at a particular moment in time. If I pay $100 for a one year, $100 par value bond that pays 5% interest then the bond yields 5% since I will receive $5 from a $100 investment if I held the bond to maturity. If I pay $90 for the same one year bond then the bond yields 17% since I will receive $15 from a $90 investment if I held the bond to maturity. There are many factors that affect what yield creditors will accept: It is the last bullet that ultimately determines yield. The other factors feed into the creditor’s desire to hold money today versus receiving money in the future. I desire money in my hand more than a promise to receive money in the future. In order to entice me to lend my money someone must offer me an incentive. Thus, they must offer me more money in the future in order for me to part with money I have. A yield curve is a snapshot of the yields for different loan durations. The x-axis is the amount of time left on the bond while the y-axis is the yield. The most cited yield curve is the US treasury curve which displays the yields for loans to the US government. The yield curve changes while bonds are being traded thus it is always a snapshot of a particular moment in time. Short term loans typically have less yield than longer term loans since there is less uncertainty about the near future. Yield curves will flatten or slightly invert when creditors desire to keep their money instead of loaning it out. This can occur because of a sudden disruption in the market that causes uncertainty about the future which leads to an increase in the demand for cash on hand. The US government yield curve should be looked at with some reservation however since there is a very large creditor to the US government that has the ability to loan the government an unlimited amount of funds.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"127434\",\n \"text\": \"You’ve really got three or four questions going here… and it’s clear that a gap in understanding one component of how bonds work (pricing) is having a ripple effect across the other facets of your question. The reality is that everybody’s answers so far touch on various pieces of your general question, but maybe I can help by integrating. So, let’s start by nailing down what your actual questions are: 1. Why do mortgage rates (tend to) increase when the published treasury bond rate increases? I’m going to come back to this, because it requires a lot of building blocks. 2. What’s the math behind a bond yield increasing (price falling?) This gets complicated, fast. Especially when you start talking about selling the bond in the middle of its time period. Many people that trade in bonds use financial calculators, Excel, or pre-calculated tables to simplify or even just approximate the value of a bond. But here’s a simple example that shows the math. Let’s say we’ve got a bond that is issued by… Dell for $10,000. The company will pay it back in 5 years, and it is offering an 8% rate. Interest payments will only be paid annually. Remember that the amount Dell has promised to pay in interest is fixed for the life of the bond, and is called the ‘coupon’ rate. We can think about the way the payouts will be paid in the following table: As I’m sure you know, the value of a bond (its yield) comes from two sources: the interest payments, and the return of the principal. But, if you as an investor paid $14,000 for this bond, you would usually be wrong. You need to ‘discount’ those amounts to take into account the ‘time value of money’. This is why when you are dealing in bonds it is important to know the ‘coupon rate’ (what is Dell paying each period?). But it is also important to know your sellers’/buyers’ own personal discount rates. This will vary from person to person and institution to institution, but it is what actually sets the PRICE you would buy this bond for. There are three general cases for the discount rate (or the MARKET rate). First, where the market rate == the coupon rate. This is known as “par” in bond parlance. Second, where the market rate < the coupon rate. This is known as “premium” in bond parlance. Third, where the market rate > coupon rate. This is known as a ‘discount’ bond. But before we get into those in too much depth, how does discounting work? The idea behind discounting is that you need to account for the idea that a dollar today is not worth the same as a dollar tomorrow. (It’s usually worth ‘more’ tomorrow.) You discount a lump sum, like the return of the principal, differently than you do a series of equal cash flows, like the stream of $800 interest payments. The formula for discounting a lump sum is: Present Value=Future Value* (1/(1+interest rate))^((# of periods)) The formula for discounting a stream of equal payments is: Present Value=(Single Payment)* (〖1-(1+i)〗^((-n))/i) (i = interest rate and n = number of periods) **cite investopedia So let’s look at how this would look in pricing the pretend Dell bond as a par bond. First, we discount the return of the $10,000 principal as (10,000 * (1 / 1.08)^5). That equals $6,807.82. Next we discount the 5 equal payments of $800 as (800* (3.9902)). I just plugged and chugged but you can do that yourself. That equals $3,192.18. You may get slightly different numbers with rounding. So you add the two together, and it says that you would be willing to pay ($6,807.82 + $3,192.18) = $10,000. Surprise! When the bond is a par bond you’re basically being compensated for the time value of money with the interest payments. You purchase the bond at the ‘face value’, which is the principal that will be returned at the end. If you worked through the math for a 6% discount rate on an 8% coupon bond, you would see that it’s “premium”, because you would pay more than the principal that is returned to obtain the bond [10,842.87 vs 10,000]. Similarly, if you work through the math for a 10% discount rate on an 8% coupon bond, it’s a ‘discount’ bond because you will pay less than the principal that is returned for the bond [9,241.84 vs 10,000]. It’s easy to see how an investor could hold our imaginary Dell bond for one year, collect the first interest payment, and then sell the bond on to another investor. The mechanics of the calculations are the same, except that one less interest payment is available, and the principal will be returned one year sooner… so N=4 in both formulae. Still with me? Now that we’re on the same page about how a bond is priced, we can talk about “Yield To Maturity”, which is at the heart of your main question. Bond “yields” like the ones you can access on CNBC or Yahoo!Finance or wherever you may be looking are actually taking the reverse approach to this. In these cases the prices are ‘fixed’ in that the sellers have listed the bonds for sale, and specified the price. Since the coupon values are fixed already by whatever organization issued the bond, the rate of return can be imputed from those values. To do that, you just do a bit of algebra and swap “present value” and “future value” in our two equations. Let’s say that Dell has gone private, had an awesome year, and figured out how to make robot unicorns that do wonderful things for all mankind. You decide that now would be a great time to sell your bond after holding it for one year… and collecting that $800 interest payment. You think you’d like to sell it for $10,500. (Since the principal return is fixed (+10,000); the number of periods is fixed (4); and the interest payments are fixed ($800); but you’ve changed the price... something else has to adjust and that is the discount rate.) It’s kind of tricky to actually use those equations to solve for this by hand… you end up with two equations… one unknown, and set them equal. So, the easiest way to solve for this rate is actually in Excel, using the function =RATE(NPER, PMT, PV, FV). NPER = 4, PMT = 800, PV=-10500, and FV=10000. Hint to make sure that you catch the minus sign in front of the present value… buyer pays now for the positive return of 10,000 in the future. That shows 6.54% as the effective discount rate (or rate of return) for the investor. That is the same thing as the yield to maturity. It specifies the return that a bond investor would see if he or she purchased the bond today and held it to maturity. 3. What factors (in terms of supply and demand) drive changes in the bond market? I hope it’s clear now how the tradeoff works between yields going UP when prices go DOWN, and vice versa. It happens because the COUPON rate, the number of periods, and the return of principal for a bond are fixed. So when someone sells a bond in the middle of its term, the only things that can change are the price and corresponding yield/discount rate. Other commenters… including you… have touched on some of the reasons why the prices go up and down. Generally speaking, it’s because of the basics of supply and demand… higher level of bonds for sale to be purchased by same level of demand will mean prices go down. But it’s not ‘just because interest rates are going up and down’. It has a lot more to do with the expectations for 1) risk, 2) return and 3) future inflation. Sometimes it is action by the Fed, as Joe Taxpayer has pointed out. If they sell a lot of bonds, then the basics of higher supply for a set level of demand imply that the prices should go down. Prices going down on a bond imply that yields will go up. (I really hope that’s clear by now). This is a common monetary lever that the government uses to ‘remove money’ from the system, in that they receive payments from an investor up front when the investor buys the bond from the Fed, and then the Fed gradually return that cash back into the system over time. Sometimes it is due to uncertainty about the future. If investors at large believe that inflation is coming, then bonds become a less attractive investment, as the dollars received for future payments will be less valuable. This could lead to a sell-off in the bond markets, because investors want to cash out their bonds and transfer that capital to something that will preserve their value under inflation. Here again an increase in supply of bonds for sale will lead to decreased prices and higher yields. At the end of the day it is really hard to predict exactly which direction bond markets will be moving, and more importantly WHY. If you figure it out, move to New York or Chicago or London and work as a trader in the bond markets. You’ll make a killing, and if you’d like I will be glad to drive your cars for you. 4. How does the availability of money supply for banks drive changes in other lending rates? When any investment organization forms, it builds its portfolio to try to deliver a set return at the lowest risk possible. As a corollary to that, it tries to deliver the maximum return possible for a given level of risk. When we’re talking about a bank, DumbCoder’s answer is dead on. Banks have various options to choose from, and a 10-year T-bond is broadly seen as one of the least risky investments. Thus, it is a benchmark for other investments. 5. So… now, why do mortgage rates tend to increase when the published treasury bond yield rate increases? The traditional, residential 30-year mortgage is VERY similar to a bond investment. There is a long-term investment horizon, with fixed cash payments over the term of the note. But the principal is returned incrementally during the life of the loan. So, since mortgages are ‘more risky’ than the 10-year treasury bond, they will carry a certain premium that is tied to how much more risky an individual is as a borrower than the US government. And here it is… no one actually directly changes the interest rate on 10-year treasuries. Not even the Fed. The Fed sets a price constraint that it will sell bonds at during its periodic auctions. Buyers bid for those, and the resulting prices imply the yield rate. If the yield rate for current 10-year bonds increases, then banks take it as a sign that everyone in the investment community sees some sign of increased risk in the future. This might be from inflation. This might be from uncertain economic performance. But whatever it is, they operate with some rule of thumb that their 30-year mortgage rate for excellent credit borrowers will be the 10-year plus 1.5% or something. And they publish their rates.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"231268\",\n \"text\": \"Companies do not support their stock. Once the security is out on the wild (market), its price fluctuates according to what investors think they are worth. Support is a whole different concept, financially speaking: Support or support level refers to the price level below which, historically, a stock has had difficulty falling. It is the level at which buyers tend to enter the stock. So it is the lowest assumed price for that stock. Once it reaches its price, buyers will rush to the stock, raising its price. The company wants to keep the stock price at acceptable levels, as it can be seen as the general view of the company's health. Also several employees/executives in the company have stock or stock options, so it is in their interest to keep their stock price up. A bond that goes down in value may indicate a believe the bond issuer (government in this case) won't honor the bond when it matures. As for bonds, there is a wealth of reading in this site: Can someone explain how government bonds work? Who sets the prices on government bonds? Basic understanding of bonds, values, rates and yields\",\n \"title\": \"\"\n },\n {\n \"docid\": \"285176\",\n \"text\": \"The assumption that bonds have been issued with a negative coupon is not correct, or at least is has not occurred thus far. We'll look at this future possibility in the final paragraph. For now, lets look at the current bond market. The issuance of government bonds which carry a negative gross redemption yield is the result of governments issuing bonds at an issue price which exceed the nominal/redemption price and any coupon yield receivable over the life of the bond. I can find no instances of bonds with a negative coupon, though many have tiny positive coupon yields. The short seller of a bond with a negative gross redemption yield will be liable to pay the buyer the interest amount determined by the coupon. If the short seller has borrowed the bonds in order to sell them, then the short seller will receive the interest due from the lender to offset the interest paid to the buyer. If the short seller has not borrowed the bonds, but has sold them using some sort of synthetic contract such as a Contract for Difference, then the short seller will pay the coupon without receiving any offsetting payment. I thought this was an interesting question and it will be interesting to see if, at some time in the future, governments do ever issue bonds with a negative coupon. To date, this does not appear to have happened. So what would happen if we assume that a government issues a bond with a negative coupon. The buyer of the bond would be required to pay the equivalent yield to the government according to the bond contract specification. If an investor sells short such a bond, they would then become entitled to receive the interest from the buyer. If they have borrowed the bonds in order to sell them short, then they would pay any interest received back to the lender - this chain should eventually end with the ultimate owner/lender paying the government their dues. If they have sold short using a synthetic contract, then presumably they would keep the interest from themselves.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"388391\",\n \"text\": \"\\\"So \\\"\\\"Operation Twist\\\"\\\" is actually a pretty simple concept. Here's the break down: The Fed sells short-term treasury bonds that it already holds on its books. Short-term treasury bonds refer to - bonds that mature in less than three years. Then: Uses that money to buy long term treasury bonds. Long-term treasury bonds refer to - bonds that mature in six to 30 years The reason: The fed buys these longer-term treasuries to lower longer-term interest rates and encourage more borrowing and spending. Diving deeper into how it works: So the Fed can easily determine short-term rates by using the Federal funds rate this rate has a direct effect on the following: However this does not play a direct role in influencing the rate of long-term loans (what you might pay on a 30-year fixed mortgage). Instead, long-term rates are determined by investors who buy and sell bonds in the bond market, which changes daily. These bond yields fluctuate depending on the health of the economy and inflation. However, the Fed funds rate does play an indirect role in these rates. So now that we know a little more about what effects what rate, why does lower long-term rates in treasuries influence my 30yr fixed mortgage? Well when you are looking for a loan you are entering a market and competing against other people, by people I mean anyone looking for money (e.g: my grandmother, companies, or the US government). The bank that lends you money has to decide weather the deal you are offering them is better then another deal on the market. If the risk of lending to one person is the same as the risk of lending to another, the bank will make whichever loan yields the higher interest rate. The U.S. government is considered a very safe borrower, so much so that government bonds are considered almost “risk free”, but because of the lower risk the rate of return is lower. So now the bank has to factor in this risk and make its decision weather to lend you money, or the government. So, if the government were to go to the market and buy its own long-term bonds it is adding demand in the market causing the price of the bond to rise in effect lowering the interest rate (when price goes up, yield goes down). So when you go back and ask for a loan it has to re-evaluate and decide \\\"\\\"Is it worth giving this money to Joe McFreeBeer instead and collecting a higher yield?\\\"\\\" (After all, Joe McFreeBeer is a nice guy). Here's an example: Lets say the US has a rating of 10 out of 10 and its bonds pay a 2% yield. Now lets say for each lower mark in rating the bank will lend at a minimum of 1% higher and your rating is 8 of 10. So if you go to market, the lowest rate you can get will be 4%. Now lets say price rises on the US treasury and causes the rate to go down by 1%. In this scenario you will now be able to get a loan for 3% and someone with a rating of 7 of 10 would be able to get that 4% loan. Here's some more info and explinations: Why is the Government Buying Long-Term Bonds? What Is 'Operation Twist'? A Q&A on US Fed Program Federal Reserve for Beginners Federal Open Market Committee\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"144177\",\n \"text\": \"\\\"If you owned a bank how would you invest the bank's money? Typically banks are involved in loaning out money to businesses, people, and government at a higher interest rate then what they are paying to depositors. This is the spread and how they make money. If the bank determines that the yields on government bonds is more attractive then loaning the money out to businesses and people then the bank will purchase government bonds. It can also decide the other way. In this manner the mortgage and bond markets are always competing for capital and tend to offer very similar yields. Certain banks have the unique privilege of being able to borrow money from the FED at the Federal Funds rate and use this money to purchase government debt or loan it out to other banks or purchase other debt products. In this manner you see a high correlation between the FED funds rate, mortgage rates, and treasury yields. Other political factors include legislation that encourages mortgage lending (see Community Reinvestment Act) where banks may not have made the loans without said legislation. In short, keep your eye on the FED and ask yourself: \\\"\\\"Does the FED want rates to rise?\\\"\\\" and \\\"\\\"Can the US government afford rising rates?\\\"\\\" The answer to these two questions is no. However, the FED may be pressured to \\\"\\\"stop the presses\\\"\\\" if inflation becomes unwieldy and the FED actually starts to care about food and energy prices. So far this hasn't been the case.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"446214\",\n \"text\": \"\\\"What is a bond price? A bond is an asset, and like any tradeable asset it has a price. If I hold $10K face value of a certain GM bond, then I would be willing to sell it at some price, which may be more or less than $10K. Whoever is willing to sell it for the lowest amount determines the price. The price is determined by the market, just as all prices are. It's what you can sell a bond for. Bond prices may be quoted in various funny ways, like as a discount or premium relative to the face value or as a premium over a treasury, but at the end it all should be converted to how much you have to pay today. In this case, it's how much you would pay today to get a set of future coupon and principal payments. What is Yield to Maturity? A bond is a contract entitling you to a certain set of predefined cash flows. If you take that set of cash flows and discount them using a single rate at all maturities such that the discounted value is equal to the price, the single rate you have identified is the YTM. Mathematically, this is the same as finding the IRR (internal rate of return) of some set of cash flows. In this case the cash flows are the coupons and principal repayment. Other bond concepts. Note that the other aspects of a bond, like maturity, coupon rate, and face value, are immutably written into the bond contract. All they do is define what payments the bond entitles the owner to. They don't say how much someone would pay today in order to be entitled to those payments. One can't know how much a future payment is worth without discounting. If you know the appropriate discount rate at every relevant maturity, you could calculate the fair price of a bond. That's the other direction. YTM looks at the market price and associated cash flows and imputes what single discount rate would make that price fair. What is YTM good for? Recall what I said about IRR above. Why would anyone want to know what discount rate equates the cash flows of a project to its cost? Because it's an easy way to summarize how profitable the project is expected to be. YTM is a quick way to summarize the yield one would get on a bond if they were to buy it today and hold to maturity. If one bond has a higher YTM than another, than heuristically we believe it pays out more and should be associated with greater risk if the market is working properly. It can be used to compare bonds or to look at how changes in bond prices are affecting expected yields. Ask yourself, how would you compare two different bonds with different maturities and coupon rates? Which one is riskier or more profitable? The simplest way to summarize this information is with the yield to maturity. YTM is used frequently enough that when you just say a bond's \\\"\\\"yield,\\\"\\\" people will assume you are talking about its yield to maturity. What is YTM not good for? One thing to be wary of is using YTM as a discount rate. It looks like a discount rate but it works for that bond and that bond only. In reality each individual coupon payment has a true discount rate, and the discount rate at each horizon is different from each other horizon. Those are true discount rates that can be applied to any cash flow of similar risk to get the right price. We can think of YTM as some kind of average of those discount rates that produces the correct price for that bond only. You should never use it for discounting something else.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"342485\",\n \"text\": \"just pick a good bond and invest all your money there (since they're fairly low risk) No. That is basically throwing away your money and why would you do that. And who told you they are low risk. That is a very wrong premise. What factors should I consider in picking a bond and how would they weigh against each other? Quite a number of them to say, assuming these aren't government bonds(US, UK etc) How safe is the institution issuing the bond. Their income, business they are in, their past performance business wise and the bonds issued by them, if any. Check for the bond ratings issued by the rating agencies. Read the prospectus and check for any specific conditions i.e. bonds are callable, bonds can be retired under certain conditions, what happens if they default and what order will you be reimbursed(senior debt take priority). Where are interest rates heading, which will decide the price you are paying for the bond. And also the yield you will derive from the bond. How do you intend to invest the income, coupon, you will derive from the bonds. What is your time horizon to invest in bonds and similarly the bond's life. I have invested in stocks previously but realized that it isn't for me Bonds are much more difficult than equities. Stick to government bonds if you can, but they don't generate much income, considering the low interest rates environment. Now that QE is over you might expect interest rates to rise, but you can only wait. Or go for bonds from stable companies i.e. GE, Walmart. And no I am not saying you buy their bonds in any imaginable way.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"395111\",\n \"text\": \"The 10yr bond pays coupons semi annually. The yield % is what you would get annually if you hold the bond to full term. The coupon payment won't be exactly 1.65%/2 because of how bond pricing and yields work. The yield commonly quoted does not tell you how much each interest payment is. You have to look at the price and coupon of a specific individual bond. The rate you see is the market equilibrium yield at the present. Example, I offer two different people two different bonds. Joe buys a 10yr bond paying 5% coupons semi annually at a par value of $1000. I charge him $1000. Bob wants to buy a 10yr bond paying 10% coupons semi annually at a par value of $1000. I charge him $1500 for this. The yield is similar between the two (not equal due to math details but lets assume). So at the end of 10 yrs, the two have roughly the same total amount of $. Bob's paid more each year but he paid more up front. This is why the federal govt can issue bonds with diff coupons and the market prices them so the yield rises/falls to the market clearing yield.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"498645\",\n \"text\": \"\\\"Bonds might not be simple, but in general there are only a few variables that need to be understood: bid, coupon (interest) rate, maturity, and yield. Bond tables clearly lay those out, and if you're talking about government bonds a lot of things (like convertibles) don't apply (although default is still a concern). This might be overly simplistic, but I view ETF's primarily as an easy way to bring somewhat esoteric instruments (like grain futures) into the easily available markets of Nasdaq and the NYSE. That they got \\\"\\\"enhanced\\\"\\\" with leveraged funds and the such is interesting, but perhaps not the original intent of the instrument. Complicating your situation a bit more is the fee that gets tacked onto the ETF. Even Vanguard government bond funds hang out north of 0.1%. That's not huge, but it's not particularly appealing either considering that (unlike rounding up live cattle futures), it's not that much work to buy US government bonds, so the expense might not seem worth it to someone who's comfortable purchasing the securities directly. I'd be interested to see someone else's view on this, but in general I'd say that if you know what you want and know how to buy it, the government bond ETF becomes a lot less relevant as the liquidity offered (including the actual \\\"\\\"ease of transacting\\\"\\\") seem to to be the biggest factors in favor. From Investopedia's description: The bond ETF is an exciting new addition to the bond market, offering an excellent alternative to self-directed investors who, looking for ease of trading and increased price transparency, want to practice indexing or active bond trading. However, bond ETFs are suitable for particular strategies. If, for instance, you are looking to create a specific income stream, bond ETFs may not be for you. Be sure to compare your alternatives before investing.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"260984\",\n \"text\": \"There are a few other factors possible here: Taxes - Something you don't mention is what are the tax rates on each of those choices. If the 4% gain is taxed at 33% while the 3% government bond is taxed at 0% then it may well make more sense to have the government bond that makes more money after taxes. Potential changes in rates - Could that 4% rate change at any time? Yield curves are an idea here to consider where at times they can become inverted where short-term bonds yield more than long-term bonds due to expectations about rates. Some banks may advertise a special rate for a limited time to try to get more deposits and then change the rate later. Beware the fine print. Could the bond have some kind of extra feature on it? For example, in the US there are bonds known as TIPS that while the interest rate may be low, there is a principal adjustment that comes as part of the inflation adjustment that is part how the security is structured.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"411966\",\n \"text\": \"\\\"The most fundamental observation of bond pricing is this: Bond price is inversely proportional to bond yields When bond yields rise, the price of the bond falls. When bond yields fall, the price of the bond rises. Higher rates are \\\"\\\"bad\\\"\\\" for bonds. If a selloff occurs in the Russian government bond space (i.e. prices are going down), the yield on that bond is going to increase as a consequence.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"538898\",\n \"text\": \"The Fed sets the overnight borrowing costs by setting its overnight target rate. The markets determine the rates at which the treasury can borrow through the issuance of bonds. The Fed's actions will certainly influence the price of very short term bonds, but the Fed's influence on anything other than very short term bonds in the current environment is very muted. Currently, the most influential factor keeping bond prices high and yields low is the high demand for US treasuries coming from overseas governments and institutions. This is being caused by two factors : sluggish growth in overseas economies and the ongoing strength of the US dollar. With many European government bonds offering negative redemption yields, income investors see US yields as relatively attractive. Those non-US economies which do not have negative bond yields either have near zero yields or large currency risks or both. Political issues such as the survival of the Euro also weigh heavily on market perceptions of the current attractiveness of the US dollar. Italian banks may be about to deliver a shock to the Eurozone, and the Spanish and French banks may not be far behind. Another factor is the continued threat of deflation. Growth is slowing around the world which negatively effects demand. Commodity prices remain depressed. Low growth and recession outside of the US translate into a prolonged period of near zero interest rates elsewhere together with renewed QE programmes in Europe, Japan, and possibly elsewhere. This makes the US look relatively attractive and so there is huge demand for US dollars and bonds. Any significant move in US interest rates risks driving to dollar ever higher which would be very negative for the future earning of US companies which rely on exports and foreign income. All of this makes the market believe that the Fed's hands are tied and low bond yields are here for the foreseeable future. Of course, even in the US growth is relatively slow and vulnerable to a loss of steam following a move in interest rates.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"587032\",\n \"text\": \"\\\"The simple answer is that, even though mortgages can go for 10, 15, 20 and 30 year terms in the U.S., they're typically backed by bonds sold to investors that mature in 10 years, which is the standard term for most bonds. These bonds, in the open market, are compared by investors with the 10-year Treasury note, which is the gold standard for low-risk investment; the U.S. Government has a solid history of always paying its bills (though this reputation is being tested in recent years with fights over the debt ceiling and government budgets). The savvy investor, therefore, knows that he or she can make at least the yield from the 10-year T-note in that time frame, with virtually zero risk. Anything else on the market is seen as being a higher risk, and so investors demand higher yields (by making lower bids, forcing the issuer to issue more bonds to get the money it needs up front). Mortgage-backed securities are usually in the next tier above T-debt in terms of risk; when backed by prime-rate mortgages they're typically AAA-rated, making them available to \\\"\\\"institutional investors\\\"\\\" like banks, mutual funds, etc. This forms a balancing act; mortgage-backed securities issuers typically can't get the yield of a T-note, because no matter how low their risk, T-debt is lower (because one bank doesn't have the power to tax the entire U.S. population). But, they're almost as good because they're still very stable, low-risk debt. This bond price, and the resulting yield, is in turn the baseline for a long-term loan by the bank to an individual. The bank, watching the market and its other bond packages, knows what it can get for a package of bonds backed by your mortgage (and others with similar credit scores). It will therefore take this number, add a couple of percentage points to make some money for itself and its stockholders (how much the bank can add is tacitly controlled by other market forces; you're allowed to shop around for the lowest rate you can get, which limits any one bank's ability to jack up rates), and this is the rate you see advertised and - hopefully - what shows up on your paperwork after you apply.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"495600\",\n \"text\": \"\\\"Question 1: How do I start? or \\\"\\\"the broker\\\"\\\" problem Get an online broker. You can do a wire transfer to fund the account from your bank. Question 2: What criticism do you have for my plan? Dividend investing is smart. The only problem is that everyone's currently doing it. There is an insatiable demand for yield, not just individual investors but investment firms and pension funds that need to generate income to fund retirements for their clients. As more investors purchase the shares of dividend paying securities, the share price goes up. As the share price goes up, the dividend yield goes down. Same for bonds. For example, if a stock pays $1 per year in dividends, and you purchase the shares at $20/each, then your yearly return (not including share price fluctuations) would be 1/20 = 5%. But if you end up having to pay $30 per share, then your yearly return would be 1/30 or 3.3% yield. The more money you invest, the bigger this difference becomes; with $100K invested you'd make about $1.6K more at 5%. (BTW, don't put all your money in any small group of stocks, you want to diversify). ETFs work the same way, where new investors buying the shares cause the custodian to purchase more shares of the underlying securities, thus driving up the price up and yield down. Instead of ETFs, I'd have a look at something called closed end funds, or CEFs which also hold an underlying basket of securities but often trade at a discount to their net asset value, unlike ETFs. CEFs usually have higher yields than their ETF counterparts. I can't fully describe the ins and outs here in this space, but you'll definately want to do some research on them to better understand what you're buying, and HOW to successfully buy (ie make sure you're buying at a historically steep discount to NAV [https://seekingalpha.com/article/1116411-the-closed-end-fund-trifecta-how-to-analyze-a-cef] and where to screen [https://www.cefconnect.com/closed-end-funds-screener] Regardless of whether you decide to buy stocks, bonds, ETFs, CEFs, sell puts, or some mix, the best advice I can give is to a) diversify (personally, with a single RARE exception, I never let any one holding account for more than 2% of my total portfolio value), and b) space out your purchases over time. b) is important because we've been in a low interest rate environment since about 2009, and when the risk free rate of return is very low, investors purchase stocks and bonds which results in lower yields. As the risk free rate of return is expected to finally start slowly rising in 2017 and gradually over time, there should be gradual downward pressure (ie selling) on the prices of dividend stocks and especially bonds meaning you'll get better yields if you wait. Then again, we could hit a recession and the central banks actually lower rates which is why I say you want to space your purchases out.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"239271\",\n \"text\": \"Big money, by vitue of its own existence, produces value. What's a person to do with it? Stuff it under a mattress and earn 0 yield? No. If you want safety, you'll put it in AAA rated US gov't bonds and help fund the government. If you want yield, you'll put it in broadly diversified equities investments, small companies, big companies, energy companies, tech companies, media companies, and so on, and soak up the net gain while injecting much needed capital investment directly into those industries, financing start up costs like construction and equipment procurement costs, as well as staffing costs. Yes, big money absolutely creates value. The trains, cars, roads, and sidewalks you travel through to get to work? All financed by filthy rich people money. The building you work in and the equipment you use? Likely financed by filthy rich people money as well. Its called financial intermediation and capital arbitrage, and you can thank your Gods you live in a country where the government allows it to operate efficiently.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"215189\",\n \"text\": \"\\\"All of the other answers here are accurate, but (I think) are missing the point as to the question, which rests on how Bonds work in the first place. The bond specifies a payback AMOUNT and DATE. Let's say it is $10,000 and one year from today. If you buy that today for $9900, your yield will be 1%. If you buy it today for $11,000, your yield will be less than 0% (please don't make me do the math - it's just under negative 1%). You might be willing to pay that 1% (rather than receive 1%) for the certainty that you will definitely get your money back. The combined actions of all the people who may be willing to pay a little more or a little less for the safety of a US Treasury Bond is what people call \\\"\\\"the Market.\\\"\\\" Market forces (generally, investor confidence) will drive the price up and down, which affects the yield. All the other stuff - coupons and inflation and whatnot - all of that only makes sense if you understand that you aren't buying a rate of return, you are buying a payback amount and date.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"97729\",\n \"text\": \"You can look at TIPS (which have some inflation protection built in). Generally short term bonds are better than long if you expect rates to rise soon. Other ways that you can protect yourself are to choose higher yield corporate bonds instead of government bonds, or to use foreign bonds. There are plenty of bond funds like Templeton Global or ETFs that offer such features. Find one that will work for you.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"227433\",\n \"text\": \"\\\"Why does the yield go up if the country is economically unstable? The yield will rise when instability increases because the risk of default increases. If the case of Greece, the instability of government finances resulted in a 50% \\\"\\\"haircut\\\"\\\" for bond holders in 2011. In other words, bond holders suffered a 50% write down in the nominal value of their bonds. This means that holding these bonds until maturity will mean they will only receive half of the original nominal value of the bond, and that is assuming no further write downs occur. Why does selling a bond drive up the yield? Significant selling of bonds means that sellers are worried about future prospects. Sellers will outnumber buyers, so sellers will have to reduce their offer price in order to attract new buyers. So if you think Greece is not going to default as it's highly likely a country would completely default, wouldn't it make sense to hold onto the bonds? If you think that it is highly unlikely that Greece will default and the prices and yields are attractive, then Greek bonds may look like an attractive investment. However, keep in mind the fate of bond holders in 2011. They were attracted to Greek bonds by the price and yield, but they suffered a 50% haircut.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"269550\",\n \"text\": \"Buy a fund of bonds, there are plenty and are registered on your stockbroker account as 'funds' rather than shares. Otherwise, to the individual investor, they can be considered as the same thing. Funds (of bonds, rather than funds that contain property or shares or other investments) are often high yield, low volatility. You buy the fund, and let the manager work it for you. He buys bonds in accordance to the specification of the fund (ie some funds will say 'European only', or 'global high yield' etc) and he will buy and sell the bonds regularly. You never hold to maturity as this is handled for you - in many cases, the manager will be buying and selling bonds all the time in order to give you a stable fund that returns you a dividend. Private investors can buy bonds directly, but its not common. Should you do it? Up to you. Bonds return, the company issuing a corporate bond will do so at a fixed price with a fixed yield. At the end of the term, they return the principal. So a 20-year bond with a 5% yield will return someone who invests £10k, £500 a year and at the end of the 20 years will return the £10k. The corporate doesn't care who holds the bond, so you can happily sell it to someone else, probably for £10km give or take. People say to invest in bonds because they do not move much in value. In financially difficult times, this means bonds are more attractive to investors as they are a safe place to hold money while stocks drop, but in good times the opposite applies, no-one wants a fund returning 5% when they think they can get 20% growth from a stock.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"457122\",\n \"text\": \"\\\"For a two year time frame, a good insured savings account or a low-cost short-term government bond fund is most likely the way I would go. Depending on the specific amount, it may also be reasonable to look into directly buying government bonds. The reason for this is simply that in such a short time period, the stock market can be extremely volatile. Imagine if you had gone all in with the money on the stock market in, say, 2007, intending to withdraw the money after two years. Take a broad stock market index of your choice and see how much you'd have got back, and consider if you'd have felt comfortable sticking to your plan for the duration. Since you would likely be focused more on preservation of capital than returns during such a relatively short period, the risk of the stock market making a major (or even relatively minor) downturn in the interim would (should) be a bigger consideration than the possibility of a higher return. The \\\"\\\"return of capital, not return on capital\\\"\\\" rule. If the stock market falls by 10%, it must go up by 11% to break even. If it falls by 25%, it must go up by 33% to break even. If you are looking at a slightly longer time period, such as the example five years, then you might want to add some stocks to the mix for the possibility of a higher return. Still, however, since you have a specific goal in mind that is still reasonably close in time, I would likely keep a large fraction of the money in interest-bearing holdings (bank account, bonds, bond funds) rather than in the stock market. A good compromise may be medium-to-high-yield corporate bonds. It shouldn't be too difficult to find such bond funds that can return a few percentage points above risk-free interest, if you can live with the price volatility. Over time and as you get closer to actually needing the money, shift the holdings to lower-risk holdings to secure the capital amount. Yes, short-term government bonds tend to have dismal returns, particularly currently. (It's pretty much either that, or the country is just about bankrupt already, which means that the risk of default is quite high which is reflected in the interest premiums demanded by investors.) But the risk in most countries' short-term government bonds is also very much limited. And generally, when you are looking at using the money for a specific purpose within a defined (and relatively short) time frame, you want to reduce risk, even if that comes with the price tag of a slightly lower return. And, as always, never put all your eggs in one basket. A combination of government bonds from various countries may be appropriate, just as you should diversify between different stocks in a well-balanced portfolio. Make sure to check the limits on how much money is insured in a single account, for a single individual, in a single institution and for a household - you don't want to chase high interest bank accounts only to be burned by something like that if the institution goes bankrupt. Generally, the sooner you expect to need the money, the less risk you should take, even if that means a lower return on capital. And the risk progression (ignoring currency effects, which affects all of these equally) is roughly short-term government bonds, long-term government bonds or regular corporate bonds, high-yield corporate bonds, stock market large cap, stock market mid and low cap. Yes, there are exceptions, but that's a resonable rule of thumb.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"462668\",\n \"text\": \"\\\"This is a hard question to answer. Government debt and mortgages are loosely related. Banks typically use yields on government bonds to determine mortgage interest rates. The banks must be able to get higher rates from the mortgage otherwise they would buy government bonds. Your question mentions default so I'm assuming a country has reneged on its promise to pay either the principal or interest on government bonds. The main thing to consider is \\\"\\\"Who does not get their money?\\\"\\\". In other words, who does the government decide not to pay. This is the important part. The government will have some money so they could pay some bond holders. They must decide who to shaft. For example, let's look at who holds Greek government debt. Around 70% of Greek government debt is held outside Greece. See table below. The Greek government could decide to default only on the debt to foreign holders. In that case the banks in France and Switzerland would take the loss on their bonds. This could cause severe problems in France and Switzerland depending on the percentage of Greek bonds that make up the banks' assets. Greek banks would still face losses, however, since the price of their Greek bond holdings would drop sharply when the government defaults. Interestingly, the losses for the Greek banks may be smaller than the losses faced by the French and Swiss banks. This is usually the favored option chosen by government since the French and Swiss don't vote in Greece. Yields on Greek government bonds would rise dramatically. If your Greek mortgage is an adjustable rate mortgage then you could see some big adjustments upward. If you live in France or Switzerland then the bank that owns your mortgage may go under if Greece defaults. During liquidation the bank will sell their assets which includes mortgages and you will probably not notice any difference in your mortgage. As I stated earlier: this is a hard question to answer since the two financial instruments involved (bonds and mortgages) are similar but may or may not be related.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"237317\",\n \"text\": \"A large number of bond holders decide to sell their bonds. If they all decide to do this at the same time then there will be a large supply of bonds being sold in the market. This will drive down the price of the bonds which will increase yields. Why do bond yields move inversely to bond prices? You purchase a $100 bond today that yields 5%. You spent $100. The very next day the same bonds are being sold with a yield of 10%. If you wanted to sell your bond to someone you would have to sell it so it competed with the new bonds being sold. You could not sell it for $100 which is what you paid for it. You would have to sell it for less than the $100 you paid for it in order for it to have the equivalent yield of the new bonds being sold with a 10% yield. This is why bond yields move inversely to bond prices. Why does rising yields increase the cost of borrowing? If someone is trying to sell new bonds they will have to sell bonds that compete with the yields of the current bonds already in the market. If yields are rising on the existing bonds then the issuer of the new bonds will have to pay higher interest rates to offer equivalent yields on the new bonds. The issuer is now paying more in interest making it more expensive to borrow money. What are the incentives for the bond vigilante to sell his/her bonds? One reason a bond holder will sell his/her bonds is they believe inflation will outpace the yield on the bond they are holding. If a bond yields 3% and inflation is at 5% then the bond holder is essentially losing purchasing power if they continue to hold onto the bond. Another reason to sell would be if the bond holder has doubts in the ability of the issuer to repay the interest and/or principal of the bond.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"131380\",\n \"text\": \"Theoretically the yield curve is an expectation of inflation, however in practice (currently) the government yield curve is an expectation of banking fear. As you put your money with the government if you think the bank is going to default. With the FED lowering the longer end and making government less attractive, operation twist should theoretically lower both long term corp bond rates and stop people from buying long gov bonds (crowding out of capital).\",\n \"title\": \"\"\n },\n {\n \"docid\": \"523140\",\n \"text\": \"G spread - you have a 5.5 year bond, you take your yield minus the yield on the 5.5y point (interpolated) of the benchmark sovereign curve. Think of G = Government. I Spread - same as G Spread but you use the relevant Swap Curve. E.g. USD bond, compare against the USD Swaps curve. I = interpolated. Z Spread - stands for zero volatility curve spread. You strip the swaps curve to get zero rates (i.e. Zero coupon rates for each tenor), then find the constant spread on top of each part of the curve's zero rates to arrive at your bond's yield. In G and I Spread, you're basically discounting the bond's cash flows using one rate (i.e. The interpolated yield on the curve). With Z Spread, you're discounting using the entire portion of the curve that's relevant to your bond's maturity.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"370121\",\n \"text\": \"I'm going to make an educated guess on #1. Money markets invest in bonds with a very short time to maturity. An MMA at a bank will be invested in government bonds. Yields on these bonds are really low right now. Thus the yield on that MMA is going to be pretty low. When you make a deposit in a savings account, the bank uses some of that money to lend back out to its customers in the form of car loans, mortgages, etc. These rates are higher, so the bank is willing to pay you a bit more than the yield MMA so they can use your money for these loans. For #2, your time window is short, so there aren't really a lot of options for you. Keeping your money where it is will actually cost you money in fees. You can do as I suggested in my comment above: close the current savings account that's hitting you with fees and open a (free) high yield savings account. You might get 1.1%. If you average $60k in the account over the next 6 months you'll earn $200-250 after taxes. You didn't ask about CDs, but lately shorter term CDs are paying less than savings accounts. Going out to a year will get you just above the rate on a high yield savings account; two years just a little more. These are outside your goal window, so they aren't an option for you.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"4180\",\n \"text\": \"\\\"I don't understand the worker mentality of accepting to be part of pension plans. The downside risk to you is ridiculously high -- you're basically making an investment that the next 30 years of corporate management and the company as a whole are going to be good. Pension plans are among the first to go.. employees that retired 20-30 years ago add no current value to the company, unless you consider that current employees are motivated by the idea of a pension or working for a company that \\\"\\\"takes care\\\"\\\" of its employees. Also, part of the reason pension funds are blowing up is that the risk-free return rate is less than 1%. I don't know who to blame or thank for that, but with government bonds now trading at negative yields in real and sometimes even absolute terms (see: Swiss yields), what else are you supposed to do?\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"462697\",\n \"text\": \"\\\"that would imply that a 30Y US Treasury bond only yields 2.78%, which is nonsensically low. Those are annualized yields. It would be more precise to say that \\\"\\\"a 30Y US Treasury bond yields 2.78% per year (annualized) over 30 years\\\"\\\", but that terminology is implied in bond markets. So if you invest $1,000 in a 30-year T-bond, you will earn roughly 2.78% in interest per year. Also note that yield is calculated as if it compounded, meaning that investing in a 30-year T-bind will give you a return that is equivalent to putting it in a savings account that earns 1.39% interest (half of 2.78%) every 6 months and compounds, meaning you earn interest on top of interest. The trade-off for these low yields is you have virtually no default risk. Unlike a company that could go bankrupt and not pay back the bond, the US Government is virtually certain to pay off these bonds because it can print or borrow more money to pay off the debts. In addition, bonds in general (and especially treasuries) have very low market risk, meaning that their value fluctuates much less that equities, even indicies. S&P 500 indices may move anywhere between -40% and 50% in any given year, while T-bonds' range of movement is much lower, between -10% and 30% historically).\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"175819\",\n \"text\": \"Your question asked about a specific time the yield curve flattened or inverted. There are other times when the yield curve inverted or flattened. You also imply in your question that investors were flocking to long term bonds which lowered their yields. I don't believe this is the case. I believe investors were fleeing from short term bonds causing the yields on short term bonds to rise to meet those of long term bonds. The chart below shows the history of yields on US bonds over time. The shaded areas are where the yield curve flattened or inverted. Notice that after 1982 it is the short term yields that rise sharply to meet or cross the yields on longer term bonds. The yields on longer term bonds move little compared to the movement in yields on the short term bonds. Thus it is investors moving out of short term bonds that cause the yield curve to flatten or invert. These investors are not moving into longer term bonds since the yields on the longer term bonds do not move much at all at these times. In fact, in 2006 the longer term bond market was only 25% of the total US public debt while short term bonds made up 75%. It would take less money to move the yields on longer term bonds than it would on short term bonds yet the longer term yields did not move near as much as short term yields. So why are investors or banks moving out of short term bonds causing their yields to rise? I believe this happens for one of two reasons: they are moving into higher yielding investments or they need to raise cash to cover bad investments. Charts and more information here.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"136515\",\n \"text\": \"\\\"Bonds still definitely have a place in many passive portfolios. While it is true that interest rates have been unusually low, yields on reasonable passive bond exposures are still around 2-4%. This is significantly better than both recent past inflation and expected inflation both of which are near zero. This is reasonable if not great return, but Bonds continue to have other nice properties like relatively low risk and diversification of stock portfolios (the \\\"\\\"offset[ing] losses\\\"\\\" you mention in the OP). So to say that bonds are \\\"\\\"no longer a good idea\\\"\\\" is certainly not correct. One could say bonds may no longer be a good idea for some people that have a particularly high risk tolerance and very high return requirements. However, to some extent, that has always been true. It is worth remembering also that there is some compelling evidence that global growth is starting to broadly slow down and many people believe that future stock returns and, in general, returns on all investments will be lower. This is much much harder to estimate than bond returns though. Depending on who you believe, bond returns may actually look relatively better than the have in the past. Edit in response to comment: Corporate bond correlation with stocks is positive but generally not very strong (except for high-yield junk bonds) so while they don't offset stock volatility (negative correlation) they do help diversify a stock portfolio. Government bonds have essentially zero correlation so they don't really offset volatility as much as just not add any. Negative correlation assets are generally called insurance and you tend to have to pay for them. So there is no free lunch here. Assets that reduce risk cost money, assets that add little risk give less return and assets that are more risky tend to give more return in the long run but you can feel the pain. The mix that is right for you depends on a lot of things, but for many people that mix involves some corporate and government bonds.\\\"\",\n \"title\": \"\"\n }\n]"}}},{"rowIdx":190,"cells":{"query_id":{"kind":"string","value":"178"},"query":{"kind":"string","value":"Birth-weight is negatively associated with breast cancer."},"positive_passages":{"kind":"list like","value":[{"docid":"16322674","text":"BACKGROUND Birth size, perhaps a proxy for prenatal environment, might be a correlate of subsequent breast cancer risk, but findings from epidemiological studies have been inconsistent. We re-analysed individual participant data from published and unpublished studies to obtain more precise estimates of the magnitude and shape of the birth size-breast cancer association. METHODS AND FINDINGS Studies were identified through computer-assisted and manual searches, and personal communication with investigators. Individual participant data from 32 studies, comprising 22,058 breast cancer cases, were obtained. Random effect models were used, if appropriate, to combine study-specific estimates of effect. Birth weight was positively associated with breast cancer risk in studies based on birth records (pooled relative risk [RR] per one standard deviation [SD] [= 0.5 kg] increment in birth weight: 1.06; 95% confidence interval [CI] 1.02-1.09) and parental recall when the participants were children (1.02; 95% CI 0.99-1.05), but not in those based on adult self-reports, or maternal recall during the woman's adulthood (0.98; 95% CI 0.95-1.01) (p for heterogeneity between data sources = 0.003). Relative to women who weighed 3.000-3.499 kg, the risk was 0.96 (CI 0.80-1.16) in those who weighed < 2.500 kg, and 1.12 (95% CI 1.00-1.25) in those who weighed > or = 4.000 kg (p for linear trend = 0.001) in birth record data. Birth length and head circumference from birth records were also positively associated with breast cancer risk (pooled RR per one SD increment: 1.06 [95% CI 1.03-1.10] and 1.09 [95% CI 1.03-1.15], respectively). Simultaneous adjustment for these three birth size variables showed that length was the strongest independent predictor of risk. The birth size effects did not appear to be confounded or mediated by established breast cancer risk factors and were not modified by age or menopausal status. The cumulative incidence of breast cancer per 100 women by age 80 y in the study populations was estimated to be 10.0, 10.0, 10.4, and 11.5 in those who were, respectively, in the bottom, second, third, and top fourths of the birth length distribution. CONCLUSIONS This pooled analysis of individual participant data is consistent with birth size, and in particular birth length, being an independent correlate of breast cancer risk in adulthood.","title":"Birth Size and Breast Cancer Risk: Re-analysis of Individual Participant Data from 32 Studies"},{"docid":"23557241","text":"BACKGROUND Emerging evidence suggests an association between female prenatal experience and her subsequent risk of developing breast cancer. Potential underlying mechanisms include variation in amounts of maternal endogenous sex hormones and growth hormones, germ-cell mutations, formation of cancer stem-cells, and other genetic or epigenetic events. We reviewed and summarised quantitatively the available data on intrauterine exposures and risk of breast cancer. METHODS We systematically searched for studies that assessed association between perinatal factors and risk of breast cancer. We reviewed separately each of the perinatal factors, including birthweight, birth length, parental age at delivery, gestational age, intrauterine exposure to diethylstilbestrol, twin membership, maternal pre-eclampsia or eclampsia, and other factors. FINDINGS We identified 57 studies published between Oct 1, 1980, and June 21, 2007. Increased risk of breast cancer was noted with increased birthweight (relative risk [RR] 1.15 [95% CI 1.09-1.21]), birth length (1.28 [1.11-1.48]), higher maternal age (1.13 [1.02-1.25]), and paternal age (1.12 [1.05-1.19]). Decreased risk of breast cancer was noted for maternal pre-eclampsia and eclampsia (0.48 [0.30-0.78]) and twin membership (0.93 [0.87-1.00]). No association was noted between risk of breast cancer and gestational age at birth (0.95 [0.71-1.26]) or maternal diethylstilbestrol treatment (1.40 [0.86-2.28]). INTERPRETATION The intrauterine environment contributes to the predisposition of women to breast cancer in adulthood. The in-utero mechanisms responsible for such predisposition need to be elucidated.","title":"Intrauterine factors and risk of breast cancer: a systematic review and meta-analysis of current evidence."},{"docid":"17450673","text":"INTRODUCTION Various perinatal factors, including birth weight, birth order, maternal age, gestational age, twin status, and parental smoking, have been postulated to affect breast cancer risk in daughters by altering the hormonal environment of the developing fetal mammary glands. Despite ample biologic plausibility, epidemiologic studies to date have yielded conflicting results. We investigated the associations between perinatal factors and subsequent breast cancer risk through meta-analyses. METHODS We reviewed breast cancer studies published from January 1966 to February 2007 that included data on birth weight, birth order, maternal age, gestational age, twin status, and maternal or paternal smoking. Meta-analyses using random effect models were employed to summarize the results. RESULTS We found that heavier birth weights were associated with increased breast cancer risk, with studies involving five categories of birth weight identifying odds ratios (ORs) of 1.24 (95% confidence interval [CI] 1.04 to 1.48) for 4,000 g or more and 1.15 (95% CI 1.04 to 1.26) for 3,500 g to 3,999 g, relative to a birth weight of 2,500 to 2,599 g. These studies provided no support for a J-shaped relationship of birthweight to risk. Support for an association with birthweight was also derived from studies based on three birth weight categories (OR 1.15 [95% CI 1.01 to 1.31] for > or =4,000 g relative to <3,000 g) and two birth weight categories (OR 1.09 [95% CI 1.02 to 1.18] for > or =3,000 g relative to <3,000 g). Women born to older mothers and twins were also at some increased risk, but the results were heterogeneous across studies and publication years. Birth order, prematurity, and maternal smoking were unrelated to breast cancer risk. CONCLUSION Our findings provide some support for the hypothesis that in utero exposures reflective of higher endogenous hormone levels could affect risk for development of breast cancer in adulthood.","title":"Intrauterine environments and breast cancer risk: meta-analysis and systematic review"},{"docid":"27123743","text":"Breast cancer may originate in utero. We reviewed the available evidence on the association between birthweight and the risk of breast cancer. To date, 26 research papers addressing this issue have been published. The majority of studies identified a positive link between birthweight and premenopausal, but not postmenopausal, breast cancer. The relative risk estimate for breast cancer comparing women with high birthweight to women with low birthweight combining all studies including both pre- and postmenopausal breast cancer was 1.23 (95% confidence interval 1.13-1.34). The mechanisms underlying this association likely include elevated levels of growth factors that may increase the number of susceptible stem cells in the mammary gland or initiate tumors through DNA mutations. Loss of imprinting (LOI) of growth hormone genes relevant for intrauterine growth, such as insulin-like growth factor 2 (IGF2), leads to abnormally high levels of these hormones evidenced by high birthweight. LOI of IGF2 has also been found in mammary tumor tissue. The role of environmental factors that stimulate such epigenetic regulation of gene expression remains to be elucidated.","title":"Role of birthweight in the etiology of breast cancer."}],"string":"[\n {\n \"docid\": \"16322674\",\n \"text\": \"BACKGROUND Birth size, perhaps a proxy for prenatal environment, might be a correlate of subsequent breast cancer risk, but findings from epidemiological studies have been inconsistent. We re-analysed individual participant data from published and unpublished studies to obtain more precise estimates of the magnitude and shape of the birth size-breast cancer association. METHODS AND FINDINGS Studies were identified through computer-assisted and manual searches, and personal communication with investigators. Individual participant data from 32 studies, comprising 22,058 breast cancer cases, were obtained. Random effect models were used, if appropriate, to combine study-specific estimates of effect. Birth weight was positively associated with breast cancer risk in studies based on birth records (pooled relative risk [RR] per one standard deviation [SD] [= 0.5 kg] increment in birth weight: 1.06; 95% confidence interval [CI] 1.02-1.09) and parental recall when the participants were children (1.02; 95% CI 0.99-1.05), but not in those based on adult self-reports, or maternal recall during the woman's adulthood (0.98; 95% CI 0.95-1.01) (p for heterogeneity between data sources = 0.003). Relative to women who weighed 3.000-3.499 kg, the risk was 0.96 (CI 0.80-1.16) in those who weighed < 2.500 kg, and 1.12 (95% CI 1.00-1.25) in those who weighed > or = 4.000 kg (p for linear trend = 0.001) in birth record data. Birth length and head circumference from birth records were also positively associated with breast cancer risk (pooled RR per one SD increment: 1.06 [95% CI 1.03-1.10] and 1.09 [95% CI 1.03-1.15], respectively). Simultaneous adjustment for these three birth size variables showed that length was the strongest independent predictor of risk. The birth size effects did not appear to be confounded or mediated by established breast cancer risk factors and were not modified by age or menopausal status. The cumulative incidence of breast cancer per 100 women by age 80 y in the study populations was estimated to be 10.0, 10.0, 10.4, and 11.5 in those who were, respectively, in the bottom, second, third, and top fourths of the birth length distribution. CONCLUSIONS This pooled analysis of individual participant data is consistent with birth size, and in particular birth length, being an independent correlate of breast cancer risk in adulthood.\",\n \"title\": \"Birth Size and Breast Cancer Risk: Re-analysis of Individual Participant Data from 32 Studies\"\n },\n {\n \"docid\": \"23557241\",\n \"text\": \"BACKGROUND Emerging evidence suggests an association between female prenatal experience and her subsequent risk of developing breast cancer. Potential underlying mechanisms include variation in amounts of maternal endogenous sex hormones and growth hormones, germ-cell mutations, formation of cancer stem-cells, and other genetic or epigenetic events. We reviewed and summarised quantitatively the available data on intrauterine exposures and risk of breast cancer. METHODS We systematically searched for studies that assessed association between perinatal factors and risk of breast cancer. We reviewed separately each of the perinatal factors, including birthweight, birth length, parental age at delivery, gestational age, intrauterine exposure to diethylstilbestrol, twin membership, maternal pre-eclampsia or eclampsia, and other factors. FINDINGS We identified 57 studies published between Oct 1, 1980, and June 21, 2007. Increased risk of breast cancer was noted with increased birthweight (relative risk [RR] 1.15 [95% CI 1.09-1.21]), birth length (1.28 [1.11-1.48]), higher maternal age (1.13 [1.02-1.25]), and paternal age (1.12 [1.05-1.19]). Decreased risk of breast cancer was noted for maternal pre-eclampsia and eclampsia (0.48 [0.30-0.78]) and twin membership (0.93 [0.87-1.00]). No association was noted between risk of breast cancer and gestational age at birth (0.95 [0.71-1.26]) or maternal diethylstilbestrol treatment (1.40 [0.86-2.28]). INTERPRETATION The intrauterine environment contributes to the predisposition of women to breast cancer in adulthood. The in-utero mechanisms responsible for such predisposition need to be elucidated.\",\n \"title\": \"Intrauterine factors and risk of breast cancer: a systematic review and meta-analysis of current evidence.\"\n },\n {\n \"docid\": \"17450673\",\n \"text\": \"INTRODUCTION Various perinatal factors, including birth weight, birth order, maternal age, gestational age, twin status, and parental smoking, have been postulated to affect breast cancer risk in daughters by altering the hormonal environment of the developing fetal mammary glands. Despite ample biologic plausibility, epidemiologic studies to date have yielded conflicting results. We investigated the associations between perinatal factors and subsequent breast cancer risk through meta-analyses. METHODS We reviewed breast cancer studies published from January 1966 to February 2007 that included data on birth weight, birth order, maternal age, gestational age, twin status, and maternal or paternal smoking. Meta-analyses using random effect models were employed to summarize the results. RESULTS We found that heavier birth weights were associated with increased breast cancer risk, with studies involving five categories of birth weight identifying odds ratios (ORs) of 1.24 (95% confidence interval [CI] 1.04 to 1.48) for 4,000 g or more and 1.15 (95% CI 1.04 to 1.26) for 3,500 g to 3,999 g, relative to a birth weight of 2,500 to 2,599 g. These studies provided no support for a J-shaped relationship of birthweight to risk. Support for an association with birthweight was also derived from studies based on three birth weight categories (OR 1.15 [95% CI 1.01 to 1.31] for > or =4,000 g relative to <3,000 g) and two birth weight categories (OR 1.09 [95% CI 1.02 to 1.18] for > or =3,000 g relative to <3,000 g). Women born to older mothers and twins were also at some increased risk, but the results were heterogeneous across studies and publication years. Birth order, prematurity, and maternal smoking were unrelated to breast cancer risk. CONCLUSION Our findings provide some support for the hypothesis that in utero exposures reflective of higher endogenous hormone levels could affect risk for development of breast cancer in adulthood.\",\n \"title\": \"Intrauterine environments and breast cancer risk: meta-analysis and systematic review\"\n },\n {\n \"docid\": \"27123743\",\n \"text\": \"Breast cancer may originate in utero. We reviewed the available evidence on the association between birthweight and the risk of breast cancer. To date, 26 research papers addressing this issue have been published. The majority of studies identified a positive link between birthweight and premenopausal, but not postmenopausal, breast cancer. The relative risk estimate for breast cancer comparing women with high birthweight to women with low birthweight combining all studies including both pre- and postmenopausal breast cancer was 1.23 (95% confidence interval 1.13-1.34). The mechanisms underlying this association likely include elevated levels of growth factors that may increase the number of susceptible stem cells in the mammary gland or initiate tumors through DNA mutations. Loss of imprinting (LOI) of growth hormone genes relevant for intrauterine growth, such as insulin-like growth factor 2 (IGF2), leads to abnormally high levels of these hormones evidenced by high birthweight. LOI of IGF2 has also been found in mammary tumor tissue. The role of environmental factors that stimulate such epigenetic regulation of gene expression remains to be elucidated.\",\n \"title\": \"Role of birthweight in the etiology of breast cancer.\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"37480103","text":"CONTEXT During pregnancy, serum levels of estrogen, progesterone, and other hormones are markedly higher than during other periods of life. Pregnancy hormones primarily are produced in the placenta, and signs of placental impairment may serve as indirect markers of hormone exposures during pregnancy. During pregnancy, these markers have been inconsistently associated with subsequent risk of breast cancer in the mother. OBJECTIVE To examine associations between indirect markers of hormonal exposures, such as placental weight and other pregnancy characteristics, and maternal risk of developing breast cancer. DESIGN AND SETTING Population-based cohort study using data from the Swedish Birth Register, the Swedish Cancer Register, the Swedish Cause of Death Register, and the Swedish Register of Population and Population Changes. PARTICIPANTS Women included in the Sweden Birth Register who delivered singletons between 1982 and 1989, with complete information on date of birth and gestational age. Women were followed up until the occurrence of breast cancer, death, or end of follow-up (December 31, 2001). Cox proportional hazards models were used to estimate associations between hormone exposures and risks of breast cancer. MAIN OUTCOME MEASURE Incidence of invasive breast cancer. RESULTS Of 314,019 women in the cohort, 2216 (0.7%) developed breast cancer during the follow-up through 2001, of whom 2100 (95%) were diagnosed before age 50 years. Compared with women who had placentas weighing less than 500 g in 2 consecutive pregnancies, the risk of breast cancer was increased among women whose placentas weighed between 500 and 699 g in their first pregnancy and at least 700 g in their second pregnancy (or vice versa) (adjusted hazard ratio, 1.82; 95% confidence interval [CI], 1.07-3.08), and the corresponding risk was doubled among women whose placentas weighed at least 700 g in both pregnancies (adjusted hazard ratio, 2.05; 95% CI, 1.15-3.64). A high birth weight (> or =4000 g) in 2 successive births was associated with an increased risk of breast cancer before but not after adjusting for placental weight and other covariates (adjusted hazard ratio, 1.10; 95% CI, 0.76-1.59). CONCLUSIONS Placental weight is positively associated with maternal risk of breast cancer. These results further support the hypothesis that pregnancy hormones are important modifiers of subsequent maternal breast cancer risk.","title":"Pregnancy characteristics and maternal risk of breast cancer."},{"docid":"5487448","text":"Birth weight is a significant predictor of breast cancer risk in adult life and mammary gland mass could be an intermediate stage in this long process. We have studied the association of birth size measurements with mammographic density, a marker of mammary gland mass. For a population-based sample of 893 postmenopausal women without previous cancer in Sweden, we retrieved information on birth size from birth records and their most recent mammography. Film mammograms of the medio-lateral oblique view were digitized and the Cumulus software was used for computer-assisted semi-automated thresholding of mammographic density. Results were analyzed using generalized linear models controlling for possible confounders. Mean percent mammographic density increased when comparing the extreme categories of birth weight (from 15.6% to 18.6%) and head circumference (from 15.5% to 20.4%), and the corresponding linear trends were statistically significant (p values 0.02 and 0.007, respectively). The associations were particularly strong when the cutoff for high versus low mammographic density was set at the relatively high value of 50%. Compared to women weighing 3001-3500 grams at birth, women with birth weights >4000g were at almost 3-fold risk of developing high mammographic density (odds ratio: 2.9, 95% confidence interval 1.1 to 7.9). No association with mammographic density was evident with respect to birth length which, however, is known to be less accurately measured. These results indicate that adult breast density, a powerful predictor of breast cancer risk, has intrauterine roots, as reflected in birth size.","title":"Birth weight and mammographic density among postmenopausal women in Sweden."},{"docid":"38784540","text":"Objective To determine whether risk factors in childhood and early adulthood affect later mammographic breast density. Methods: Subjects were 628 women who attended a medical examination at the University of Glasgow Student Health Service (1948–1968), responded to a questionnaire (2001) and had a screening mammogram in Scotland (1989–2002). Mammograms (median age of 59years) were classified using a six category classification (SCC) of breast density percent. Logistic regression was used to determine associations between risk factors and having a high-risk mammogram (≥25 dense). Results: In multi-variable analyses, high-risk mammograms were associated with parity (adjusted odds ratio (OR) per child: 0.77 (95 confidence interval (CI) 0.61–0.99)), age at first birth, OR per year: 1.05 (0.99–1.11), smoking at university, OR smokers versus non-smokers: 0.58 (0.36–0.92) and body mass index (BMI) while at university, OR per 1kg/m20.75 (0.69–0.82). No associations with SCC were found for age at menarche, birth weight, oral contraceptive (OC) use, height, leg length or exercise at age 20. Conclusions: We confirm previous findings that breast density is affected by reproductive events and some anthropometric measures, however most of the risk factors acting throughout the life course which we examined were not closely related to adult breast density.","title":"Life course breast cancer risk factors and adult breast density (United Kingdom)"},{"docid":"22007333","text":"Menstrual and reproductive factors may increase breast cancer risk through a pathway that includes increased mammographic density. We assessed whether known or suspected menstrual and reproductive breast cancer risk factors were cross-sectionally associated with mammographic density, by measuring area of radiographic density and total breast area on mammograms from 801 participants in the Study of Women’s Health Across the Nation (SWAN), a multi-ethnic cohort of pre- and early perimenopausal women. From multivariable linear regression, the following menstrual or reproductive factors were independently associated with percent mammographic density (area of dense breast/breast area): older age at menarche (β = 10.3, P < 0.01, for >13 vs. <12 years), premenstrual cravings and bloating (β = −3.36, P = 0.02), younger age at first full-term birth (β = −8.12, P < 0.01 for ≤23 years versus no births), greater number of births (β = −6.80, P < 0.01 for ≥3 births versus no births), and premenopausal status (β = 3.78, P < 0.01 versus early perimenopausal). Only number of births remained associated with percent density after adjustment for age, race/ethnicity, study site, body mass index (BMI), and smoking. In addition, stratified analyses revealed that the association with number of births was confined to women within the lowest BMI tertile (β = −12.2, P < 0.01 for ≥3 births versus no births). Our data support a mechanism for parity and breast cancer that involves mammographic density among pre- and early perimenopausal women that may be modified by body size.","title":"Menstrual and reproductive factors in relation to mammographic density: the Study of Women’s Health Across the Nation (SWAN)"},{"docid":"13765757","text":"Ages at menarche and first birth are established risk factors for breast cancer. The interval between these ages may also affect risk, since the breast is more susceptible to carcinogenic insults during this period than during the parous period. However, few investigators have studied this relation. Using logistic regression, the authors evaluated associations between the timing of reproductive events and breast cancer risk among 4,013 cases and 4,069 controls enrolled in a multicenter, population-based US case-control study of White and African-American women (1994-1998). For White, parous premenopausal and postmenopausal women, those who had an interval of > or =16 years between the ages of menarche and first birth had 1.5-fold (95% confidence interval (CI): 1.0, 2.2) and 1.4-fold (95% CI: 1.1, 1.8) increased risks of breast cancer, respectively, in comparison with those who had < or =5 years between these ages. Adjusting for age at first birth altered these risk estimates somewhat, to odds ratios of 1.5 (95% CI: 0.8, 2.9) and 1.0 (95% CI: 0.6, 1.5), respectively. These associations were stronger for lobular and hormone-receptor-positive tumors but were absent among premenopausal African-American women. The authors conclude that the interval between age at menarche and age at first birth is associated with the risk of hormonally sensitive types of breast cancer, particularly among White women.","title":"Timing of menarche and first full-term birth in relation to breast cancer risk."},{"docid":"16098747","text":"Evaluate known breast cancer risk factors in relation to breast density. We examined factors in relation to breast density in 144,018 New Hampshire (NH) women with at least one mammogram recorded in a statewide mammography registry. Mammographic breast density was measured by radiologists using the BI-RADS classification; risk factors of interest were obtained from patient intake forms and questionnaires. Initial analyses showed a strong inverse influence of age and body mass index (BMI) on breast density. In addition, women with late age at menarche, late age at first birth, premenopausal women, and those currently using hormone therapy (HT) tended to have higher breast density, while those with greater parity tended to have less dense breasts. Analyses stratified on age and BMI suggested interactions, which were formally assessed in a multivariable model. The impact of current HT use, relative to nonuse, differed across age groups, with an inverse association in younger women, and a positive association in older women (p < 0.0001 for the interaction). The positive effects of age at menarche and age at first birth, and the inverse influence of parity were less apparent in women with low BMI than in those with high BMI (p = 0.04, p < 0.0001 and p = 0.01, respectively, for the interactions). We also noted stronger positive effects for age at first birth in postmenopausal women (p = 0.004 for the interaction). The multivariable model indicated a slight positive influence of family history of breast cancer. The influence of age at menarche and reproductive factors on breast density is less evident in women with high BMI. Density is reduced in young women using HT, but increased in HT users of age 50 or more.","title":"Breast cancer risk factors in relation to breast density (United States)"},{"docid":"13831842","text":"The association between anthropometric indices and the risk of breast cancer was analyzed using pooled data from seven prospective cohort studies. Together, these cohorts comprise 337,819 women and 4,385 incident invasive breast cancer cases. In multivariate analyses controlling for reproductive, dietary, and other risk factors, the pooled relative risk (RR) of breast cancer per height increment of 5 cm was 1.02 (95% confidence interval (CI): 0.96, 1.10) in premenopausal women and 1.07 (95% CI: 1.03, 1.12) in postmenopausal women. Body mass index (BMI) showed significant inverse and positive associations with breast cancer among pre- and postmenopausal women, respectively; these associations were nonlinear. Compared with premenopausal women with a BMI of less than 21 kg/m2, women with a BMI exceeding 31 kg/m2 had an RR of 0.54 (95% CI: 0.34, 0.85). In postmenopausal women, the RRs did not increase further when BMI exceeded 28 kg/m2; the RR for these women was 1.26 (95% CI: 1.09, 1.46). The authors found little evidence for interaction with other breast cancer risk factors. Their data indicate that height is an independent risk factor for postmenopausal breast cancer; in premenopausal women, this relation is less clear. The association between BMI and breast cancer varies by menopausal status. Weight control may reduce the risk among postmenopausal women.","title":"Pooled analysis of prospective cohort studies on height, weight, and breast cancer risk."},{"docid":"3285322","text":"PURPOSE Mutations in the BRCA1 and BRCA2 genes confer greater risk of developing breast cancer. We determined whether tumor pathologic features and clinical features differ in patients with and without BRCA mutations. PATIENTS AND METHODS Tumor pathologic features and clinical characteristics were examined in 491 women with breast cancer who underwent genetic testing for BRCA mutations between 1997 and 2006. A retrospective review of medical records was conducted to determine clinical characteristics including ethnicity, age and clinical stage at diagnosis, age at parity, number of full-term pregnancies, use of oral contraceptives and hormone replacement therapy, and BRCA mutation status. Tumor pathology was reviewed to determine histologic type, tumor grade, and estrogen receptor, progesterone receptor, and HER-2/neu status. RESULTS Of the 491 patients with identified breast cancers, 391 patients were BRCA negative, and 86 patients were BRCA positive. Triple-negative breast cancer (ie, those with negative estrogen receptor, progesterone receptor, and HER-2/neu status) was diagnosed in 57.1% of the BRCA1-positive patients, 23.3% of the BRCA2-positive patients, and 13.8% of the BRCA-negative patients. BRCA1 mutation carriers had higher nuclear grade tumors than the other two groups (P < .001). Of the triple-negative cancer patients, BRCA2 mutation carriers were older when diagnosed than BRCA1 mutation carriers and noncarriers (P < .01). CONCLUSION These results suggest that tumors associated with BRCA1 mutations may be divided into two distinct groups, triple-negative and non-triple-negative groups. Future studies should seek to determine whether patients with BRCA1 mutations and triple-negative breast cancer respond to treatment better than BRCA-negative patients with similar tumor pathology.","title":"Clinical and pathologic characteristics of patients with BRCA-positive and BRCA-negative breast cancer."},{"docid":"13831558","text":"BACKGROUND Extensive mammographic density is associated with an increased risk of breast cancer and makes the detection of cancer by mammography difficult, but the influence of density on risk according to method of cancer detection is unknown. METHODS We carried out three nested case-control studies in screened populations with 1112 matched case-control pairs. We examined the association of the measured percentage of density in the baseline mammogram with risk of breast cancer, according to method of cancer detection, time since the initiation of screening, and age. RESULTS As compared with women with density in less than 10% of the mammogram, women with density in 75% or more had an increased risk of breast cancer (odds ratio, 4.7; 95% confidence interval [CI], 3.0 to 7.4), whether detected by screening (odds ratio, 3.5; 95% CI, 2.0 to 6.2) or less than 12 months after a negative screening examination (odds ratio, 17.8; 95% CI, 4.8 to 65.9). Increased risk of breast cancer, whether detected by screening or other means, persisted for at least 8 years after study entry and was greater in younger than in older women. For women younger than the median age of 56 years, 26% of all breast cancers and 50% of cancers detected less than 12 months after a negative screening test were attributable to density in 50% or more of the mammogram. CONCLUSIONS Extensive mammographic density is strongly associated with the risk of breast cancer detected by screening or between screening tests. A substantial fraction of breast cancers can be attributed to this risk factor.","title":"Mammographic density and the risk and detection of breast cancer."},{"docid":"313403","text":"The tumor microenvironment is composed of tumor cells, fibroblasts, endothelial cells and infiltrating immune cells, which may inhibit or promote tumor growth and progression. The objectives of this retrospective study were to characterize the density of tumor-associated macrophages (TAMs) in breast cancer, and to correlate the density of TAMs with clinicopathological parameters. Paraffin-embedded specimens and clinicopathological data, including up to 5 years follow-up information, were obtained from 172 breast cancer patients. Immunohistochemical staining for CD68 (marker for macrophages) was performed and evaluated in a blinded fashion. We found that TAMs were significantly frequent in high histopathological grade breast cancer patients. Breast cancer patients with a high density of TAMs had significantly lower rates of disease-free survival and 5-year overall survival than patients with low density of TAMs. Furthermore, high-infiltration of TAMs indicated worse survival rate for patients with node-negative breast cancer. In conclusion, the number of TAMs in the tumor stroma is an independent predictor of survival time for breast cancer patients. High-infiltration of TAMs is a significant unfavorable prognostic factor for patients with invasive breast cancer and, as such, is a potentially useful prognostic marker for breast cancer.","title":"High-Infiltration of Tumor-Associated Macrophages Predicts Unfavorable Clinical Outcome for Node-Negative Breast Cancer"},{"docid":"25973484","text":"Obesity has a complicated relationship to both breast cancer risk and the clinical behavior of the established disease. In postmenopausal women, particularly the elderly, various measures of obesity have been positively associated with risk. However, before menopause increased body weight is inversely related to breast cancer risk. In both premenopausal and postmenopausal breast cancer, the mechanisms by which body weight and obesity affect risk have been related to estrogenic activity. Obesity has also been related to advanced disease at diagnosis and with a poor prognosis in both premenopausal and postmenopausal breast cancer. Breast cancer in African-American women, considering its relationship to obesity, exhibits some important differences from those described in white women, although the high prevalence of obesity in African-American women may contribute to the relatively poor prognosis compared with white American women. Despite the emphasis on estrogens to explain the effects of obesity on breast cancer, other factors may prove to be equally or more important, particularly as they relate to expression of an aggressive tumor phenotype. Among these, this review serves to stress insulin, insulin-like growth factor-I, and leptin, and their relationship to angiogenesis, and transcriptional factors.","title":"Breast cancer and obesity: an update."},{"docid":"1171121","text":"A considerable subgroup of patients with early breast cancer does not address benefits of anthracycline based chemotherapy. The aim of this retrospective study was to investigate the effect of microvessel density (MVD) and status of p53 protein on 5-year disease free survival (DFS) in the group of breast cancer patients treated with anthracyclines in adjuvant setting. Correlations between MVD, p53 status and other clinicopathological parameters were also assessed. MVD and p53 status were analyzed immunohistochemically in the group of 172 women with breast cancer in clinical stage T1-2, N1-N2, M0. There were 123 tumors (71.5 %) with lower MVD (≤ 214.8 microvesells/mm(2)) and 49 (28.5 %) with higher MVD (>214.8 microvesells/mm(2)). The proportion of higher MVD tumors significantly increased in N2 (P = 0.000) and in estrogen (P = 0.046) or progesterone receptors (P = 0.029) negative tumors. p53 positivity was indicated in 50 cancers (29.1 %) and was significantly associated with higher grade (P = 0.000), steroid receptors negativity (P = 0.000), cytokeratin5/6 positivity (P = 0.026), topoisomerase IIα overexpression (P = 0.005) and higher proliferation rate (P = 0.001). In univariate analysis, higher MVD (P = 0.016) and p53 negativity (P = 0.023) were significantly related with longer DFS (median follow-up 36 months). In multivariate Cox regression analysis MVD was independently associated with DFS. These data suggest that higher MVD is favourable prognostic factors for early advanced breast cancer patients after adjuvant anthracycline based chemotherapy.","title":"Microvessel Density and Status of p53 Protein as Potential Prognostic Factors for Adjuvant Anthracycline Chemotherapy in Retrospective Analysis of Early Breast Cancer Patients Group"},{"docid":"20280410","text":"Inherited mutations in the gene BRCA2 predispose carriers to early onset breast cancer, but such mutations account for fewer than 2% of all cases in East Anglia. It is likely that low penetrance alleles explain the greater part of inherited susceptibility to breast cancer; polymorphic variants in strongly predisposing genes, such as BRCA2, are candidates for this role. BRCA2 is thought to be involved in DNA double strand break-repair. Few mice in which Brca2 is truncated survive to birth; of those that do, most are male, smaller than their normal littermates and have high cancer incidence. Here we show that a common human polymorphism (N372H) in exon 10 of BRCA2 confers an increased risk of breast cancer: the HH homozygotes have a 1.31-fold (95% CI, 1.07–1.61) greater risk than the NN group. Moreover, in normal female controls of all ages there is a significant deficiency of homozygotes compared with that expected from Hardy-Weinberg equilibrium, whereas in males there is an excess of homozygotes: the HH group has an estimated fitness of 0.82 in females and 1.38 in males. Therefore, this variant of BRCA2 appears also to affect fetal survival in a sex-dependent manner.","title":"A common variant in BRCA2 is associated with both breast cancer risk and prenatal viability"},{"docid":"5222182","text":"Understanding which factors influence mammographically dense and nondense areas is important because percent mammographic density adjusted for age is a strong, continuously distributed risk factor for breast cancer, especially when adjusted for weight or body mass index. Using computer-assisted methods, we measured mammographically dense areas for 571 monozygotic and 380 dizygotic Australian and North American twin pairs ages 40 to 70 years. We used a novel regression modeling approach in which each twin's measure of dense and nondense area was regressed against one or both of the twin's and co-twin's covariates. The nature of changes to regression estimates with the inclusion of the twin and/or co-twin's covariates can be evaluated for consistency with causal and/or other models. By causal, we mean that if it were possible to vary a covariate experimentally then the expected value of the outcome measure would change. After adjusting for the individual's weight, the co-twin associations with weight were attenuated, consistent with a causal effect of weight on mammographic measures, which in absolute log cm(2)/kg was thrice stronger for nondense than dense area. After adjusting for weight, later age at menarche, and greater height were associated with greater dense and lesser nondense areas in a manner inconsistent with causality. The associations of dense and nondense areas with parity are consistent with a causal effect and/or within-person confounding. The associations between mammographic density measures and height are consistent with shared early life environmental factors that predispose to both height and percent mammographic density and possibly breast cancer risk.","title":"Predictors of mammographic density: insights gained from a novel regression analysis of a twin study."},{"docid":"16701509","text":"BACKGROUND The prevalence of metabolic syndrome (obesity, glucose intolerance, low serum high-density lipoprotein cholesterol [HDL-C], high serum triglycerides, hypertension) is high and increasing in parallel with an increasing breast cancer incidence worldwide. HDL-C represents an important aspect of the syndrome, yet its role in breast cancer is still undefined. METHODS In two population-based screening surveys during 1977-1983 and 1985-1987, serum HDL-C was assayed enzymatically among 38,823 Norwegian women aged 17-54 years at entry. Height, weight, blood pressure, serum lipids, fat and energy intake, physical activity, parity, oral contraceptive use, hormone therapy use, alcohol intake, and tobacco use were also assessed. We used Cox proportional hazards modeling to estimate the relative risk (RR) of breast cancer associated with serum HDL-C levels and to adjust for potential confounding variables. We performed stratified analyses to evaluate effect modification by body mass index (BMI) and menopausal status. All statistical tests were two-sided. RESULTS During a median follow-up of 17.2 years, we identified 708 cases of invasive breast cancer. In multivariable analysis, the risk of postmenopausal breast cancer was inversely related to quartile of HDL-C (P(trend) =.02). Among women with HDL-C above 1.64 mmol/L (highest quartile) versus below 1.20 mmol/L (lowest quartile), the relative risk was 0.75 (95% confidence interval [CI] = 0.58 to 0.97). The HDL-C association was confined to women in the heavier subgroup (BMI > or =25 kg/m2), for whom the relative risk of postmenopausal breast cancer in those with HDL-C above 1.64 mmol/L versus below 1.20 mmol/L was 0.43 (95% CI = 0.28 to 0.67; P(trend)<.001; P(interaction) =.001). CONCLUSION Low HDL-C, as part of the metabolic syndrome, is associated with increased postmenopausal breast cancer risk.","title":"Serum high-density lipoprotein cholesterol, metabolic profile, and breast cancer risk."},{"docid":"18340282","text":"BACKGROUND Information is scarce about the combined effects on breast cancer incidence of low-penetrance genetic susceptibility polymorphisms and environmental factors (reproductive, behavioural, and anthropometric risk factors for breast cancer). To test for evidence of gene-environment interactions, we compared genotypic relative risks for breast cancer across the other risk factors in a large UK prospective study. METHODS We tested gene-environment interactions in 7610 women who developed breast cancer and 10 196 controls without the disease, studying the effects of 12 polymorphisms (FGFR2-rs2981582, TNRC9-rs3803662, 2q35-rs13387042, MAP3K1-rs889312, 8q24-rs13281615, 2p-rs4666451, 5p12-rs981782, CASP8-rs1045485, LSP1-rs3817198, 5q-rs30099, TGFB1-rs1982073, and ATM-rs1800054) in relation to prospectively collected information about ten established environmental risk factors (age at menarche, parity, age at first birth, breastfeeding, menopausal status, age at menopause, use of hormone replacement therapy, body-mass index, height, and alcohol consumption). FINDINGS After allowance for multiple testing none of the 120 comparisons yielded significant evidence of a gene-environment interaction. By contrast with previous suggestions, there was little evidence that the genotypic relative risks were affected by use of hormone replacement therapy, either overall or for oestrogen-receptor-positive disease. Only one of the 12 polymorphisms was correlated with any of the ten other risk factors: carriers of the high-risk C allele of MAP3K1-rs889312 were significantly shorter than non-carriers (mean height 162.4 cm [95% CI 162.1-162.7] vs 163.1 cm [162.9-163.2]; p=0.01 after allowance for multiple testing). INTERPRETATION Risks of breast cancer associated with low-penetrance susceptibility polymorphisms do not vary significantly with these ten established environmental risk factors. FUNDING Cancer Research UK and the UK Medical Research Council.","title":"Gene–environment interactions in 7610 women with breast cancer: prospective evidence from the Million Women Study"},{"docid":"27240667","text":"PURPOSE Since 1990, overall breast cancer mortality rates in the United States decreased 24%. This decline has been attributed to mammography screening and adjuvant systemic therapy. However, the efficacy of these modalities may depend on estrogen receptor (ER) expression and age. We therefore examined breast cancer mortality trends in the United States according to ER status and age. METHODS Using the Surveillance, Epidemiology, and End Results (SEER) program (1990-2003), we calculated trends in incidence-based mortality (IBM), annual hazard rates for breast cancer deaths after diagnosis, and relative hazard rates for women with ER-positive and ER-negative tumors. Relative hazard rates were assessed with Cox proportional hazards models, adjusted for stage and grade, and stratified by age at diagnosis. RESULTS During the study period, IBM and annual hazard rates for breast cancer deaths decreased among women with ER-positive and ER-negative tumors, although declines were greater for those with ER-positive tumors. Among women younger than 70 years, relative hazard rates declined 38% for those with ER-positive tumors versus 19% for those with ER-negative tumors. Among women 70 years or older, relative hazard rates declined 14% for those with ER-positive tumors versus no significant decline for those with ER-negative tumors. CONCLUSION In the United States, breast cancer mortality rates have declined among women with ER-positive and ER-negative tumors, with greater declines among younger women and those with ER-positive tumors. Although mortality in all groups remains unacceptably high, additional emphasis should be placed on improving outcomes of breast cancer patients older than 70 years and those of all ages with ER-negative tumors.","title":"Breast cancer mortality trends in the United States according to estrogen receptor status and age at diagnosis."},{"docid":"12762485","text":"AIM Several studies have investigated the expression of the cytokeratins (CKs), vimentin, the epithelial growth factor receptor (EGFR), the oestrogen receptor (ER), and the progesterone receptor (PgR), in breast cancer, but no study has directly compared p53 mutations with these phenotypic and differentiation markers in the same case. The present study was designed to provide some of this information. METHODS The expression of the p53 and bcl-2 proteins was evaluated by immunohistochemistry in relation to phenotypic characteristics and cellular kinetic parameters (mitotic index and apoptotic index) in 37 cases of ductal carcinoma in situ (DCIS) and 27 cases of infiltrating ductal carcinoma (IDC) of the breast. In addition, p53 gene mutation was examined by polymerase chain reaction single strand conformation polymorphism analysis (SSCP). RESULTS Thirteen cases (eight DCIS and five IDC) showed expression of CK8, CK14, CK18, vimentin, and EGFR, consistent with a stem cell phenotype, whereas 44 cases (27 DCIS and 17 IDC) showed expression of CK8 and CK1, weak or negative expression of CK18, but were negative for vimentin and EGFR, consistent with a luminal cell phenotype. DCIS and IDC cases with a stem cell phenotype were ER/PgR negative and intermediately or poorly differentiated. In contrast, the cases with luminal cell phenotype were ER/PgR positive and well or intermediately differentiated. In addition, intermediately or poorly differentiated cases with a stem cell phenotype showed higher proliferative activity (per cent of MIB-l positive cells) than did intermediately or well differentiated cases with a luminal cell phenotype. Both DCIS and IDC cases with a stem cell phenotype were p53 positive and bcl-2 negative by immunohistochemistry. In IDC, p53 expression was associated with a reduction of both mitotic index and apoptotic index compared with DCIS. Most of the tumours showing a more differentiated phenotype (luminal) were p53 negative and bcl-2 positive. In these cases, cell kinetic parameters increased from DCIS to IDC. These data suggest the existence of subsets of DCIS and IDC that, because of their phenotypic characteristics, could be derived from subpopulations of normal breast cells having different control mechanisms of cell proliferation and neoplastic progression. CONCLUSIONS These results are compatible with the hypothesis that the phenotype of the cell of origin constrains both tumour phenotype and the choice of genetic events; however, the occurrence of p53 mutants by chance during neoplastic transformation cannot be excluded.","title":"p53 mutation in breast cancer. Correlation with cell kinetics and cell of origin."},{"docid":"4828631","text":"BACKGROUND High body-mass index (BMI) predisposes to several site-specific cancers, but a large-scale systematic and detailed characterisation of patterns of risk across all common cancers adjusted for potential confounders has not previously been undertaken. We aimed to investigate the links between BMI and the most common site-specific cancers. METHODS With primary care data from individuals in the Clinical Practice Research Datalink with BMI data, we fitted Cox models to investigate associations between BMI and 22 of the most common cancers, adjusting for potential confounders. We fitted linear then non-linear (spline) models; investigated effect modification by sex, menopausal status, smoking, and age; and calculated population effects. FINDINGS 5·24 million individuals were included; 166,955 developed cancers of interest. BMI was associated with 17 of 22 cancers, but effects varied substantially by site. Each 5 kg/m(2) increase in BMI was roughly linearly associated with cancers of the uterus (hazard ratio [HR] 1·62, 99% CI 1·56-1·69; p<0·0001), gallbladder (1·31, 1·12-1·52; p<0·0001), kidney (1·25, 1·17-1·33; p<0·0001), cervix (1·10, 1·03-1·17; p=0·00035), thyroid (1·09, 1·00-1·19; p=0·0088), and leukaemia (1·09, 1·05-1·13; p≤0·0001). BMI was positively associated with liver (1·19, 1·12-1·27), colon (1·10, 1·07-1·13), ovarian (1·09, 1.04-1.14), and postmenopausal breast cancers (1·05, 1·03-1·07) overall (all p<0·0001), but these effects varied by underlying BMI or individual-level characteristics. We estimated inverse associations with prostate and premenopausal breast cancer risk, both overall (prostate 0·98, 0·95-1·00; premenopausal breast cancer 0·89, 0·86-0·92) and in never-smokers (prostate 0·96, 0·93-0·99; premenopausal breast cancer 0·89, 0·85-0·94). By contrast, for lung and oral cavity cancer, we observed no association in never smokers (lung 0·99, 0·93-1·05; oral cavity 1·07, 0·91-1·26): inverse associations overall were driven by current smokers and ex-smokers, probably because of residual confounding by smoking amount. Assuming causality, 41% of uterine and 10% or more of gallbladder, kidney, liver, and colon cancers could be attributable to excess weight. We estimated that a 1 kg/m(2) population-wide increase in BMI would result in 3790 additional annual UK patients developing one of the ten cancers positively associated with BMI. INTERPRETATION BMI is associated with cancer risk, with substantial population-level effects. The heterogeneity in the effects suggests that different mechanisms are associated with different cancer sites and different patient subgroups. FUNDING National Institute for Health Research, Wellcome Trust, and Medical Research Council.","title":"Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5·24 million UK adults"},{"docid":"20839751","text":"Apoptosis is a frequent phenomenon in breast cancer and it can be detected by light microscopy in conventional histopathological sections or by special staining techniques. The number of apoptotic cells as a percentage of cells present, or the number of apoptotic cells per square millimetre of neoplastic tissue, is usually described as the apoptotic index (AI). In breast cancer, the AI is not related to tumour size, axillary lymph node metastasis or distant metastasis at diagnosis. It is greater in invasive ductal carcinomas than in other histological types. High AI is also related to high histological grade, high nuclear grade, comedo-type necrosis, lack of tubule formation, and dense infiltration of the tumour by lymphocytes. Sex steroid receptor-negative tumours have greater AIs than the sex steroid receptor-positive ones. Aneuploid breast cancers with high S-phase fractions (SPFs) also have high AI values compared with diploid tumours with low SPFs. p53-Positive breast cancers have high AIs, whereas tumours that are Bcl-2 positive have low AIs. The AI shows a strong positive correlation to all direct or indirect indicators of cell proliferation, such as mitotic index and Ki67 immunolabelling. Univariate survival analyses show that a high AI is linked with unfavourable disease outcome in axillary lymph node-negative and -positive breast cancer, but multivariate analyses indicate that AI is not an independent prognostic factor. In conclusion, a high AI is related to malignant cellular features and indicators of invasiveness and cell proliferation in breast cancer.","title":"Apoptosis in breast cancer: relationship with other pathological parameters."},{"docid":"2425364","text":"OBJECTIVE To assess the effect of 25-hydroxyvitamin D (25-OHD) levels on pregnancy outcomes and birth variables. DESIGN Systematic review and meta-analysis. DATA SOURCES Medline (1966 to August 2012), PubMed (2008 to August 2012), Embase (1980 to August 2012), CINAHL (1981 to August 2012), the Cochrane database of systematic reviews, and the Cochrane database of registered clinical trials. STUDY SELECTION Studies reporting on the association between serum 25-OHD levels during pregnancy and the outcomes of interest (pre-eclampsia, gestational diabetes, bacterial vaginosis, caesarean section, small for gestational age infants, birth weight, birth length, and head circumference). DATA EXTRACTION Two authors independently extracted data from original research articles, including key indicators of study quality. We pooled the most adjusted odds ratios and weighted mean differences. Associations were tested in subgroups representing different patient characteristics and study quality. RESULTS 3357 studies were identified and reviewed for eligibility. 31 eligible studies were included in the final analysis. Insufficient serum levels of 25-OHD were associated with gestational diabetes (pooled odds ratio 1.49, 95% confidence interval 1.18 to 1.89), pre-eclampsia (1.79, 1.25 to 2.58), and small for gestational age infants (1.85, 1.52 to 2.26). Pregnant women with low serum 25-OHD levels had an increased risk of bacterial vaginosis and low birthweight infants but not delivery by caesarean section. CONCLUSION Vitamin D insufficiency is associated with an increased risk of gestational diabetes, pre-eclampsia, and small for gestational age infants. Pregnant women with low 25-OHD levels had an increased risk of bacterial vaginosis and lower birth weight infants, but not delivery by caesarean section.","title":"Association between maternal serum 25-hydroxyvitamin D level and pregnancy and neonatal outcomes: systematic review and meta-analysis of observational studies."},{"docid":"3524352","text":"High breast cancer mortality rates have been reported in the northeastern part of the United States, with recent attention focused on Long Island, New York. In this study, the authors investigate whether the high breast cancer mortality is evenly spread over the Northeast, in the sense that any observed clusters of deaths can be explained by chance alone, or whether there are clusters of statistical significance. Demographic data and age-specific breast cancer mortality rates for women were obtained for all 244 counties in 11 northeastern states and for the District of Columbia for 1988-1992. A recently developed spatial scan statistic is used, which searches for clusters of cases without specifying their size or location ahead of time, and which tests for their statistical significance while adjusting for the multiple testing inherent in such a procedure. The basic analysis is adjusted for age, with further analyses examining how the results are affected by incorporating race, urbanicity, and parity as confounding variables. There is a statistically significant and geographically broad cluster of breast cancer deaths in the New York City-Philadelphia, Pennsylvania, metropolitan area (p = 0.0001), which has a 7.4% higher mortality rate than the rest of the Northeast. The cluster remains significant when race, urbanicity, and/or parity are included as confounding variables. Four smaller subclusters within this area are also significant on their own strength: Philadelphia with suburbs (p = 0.0001), Long Island (p = 0.0001), central New Jersey (p = 0.0001), and northeastern New Jersey (p = 0.0001). The elevated breast cancer mortality on Long Island might be viewed less as a unique local phenomenon and more as part of a more general situation involving large parts of the New York City-Philadelphia metropolitan area. The several known and hypothesized risk factors for which we could not adjust and that may explain the detected cluster are most notably age at first birth, age at menarche, age at menopause, breastfeeding, genetic mutations, and environmental factors.","title":"Breast cancer clusters in the northeast United States: a geographic analysis."},{"docid":"8529693","text":"In this paper we review the associations between maternal and child undernutrition with human capital and risk of adult diseases in low-income and middle-income countries. We analysed data from five long-standing prospective cohort studies from Brazil, Guatemala, India, the Philippines, and South Africa and noted that indices of maternal and child undernutrition (maternal height, birthweight, intrauterine growth restriction, and weight, height, and body-mass index at 2 years according to the new WHO growth standards) were related to adult outcomes (height, schooling, income or assets, offspring birthweight, body-mass index, glucose concentrations, blood pressure). We undertook systematic reviews of studies from low-income and middle-income countries for these outcomes and for indicators related to blood lipids, cardiovascular disease, lung and immune function, cancers, osteoporosis, and mental illness. Undernutrition was strongly associated, both in the review of published work and in new analyses, with shorter adult height, less schooling, reduced economic productivity, and--for women--lower offspring birthweight. Associations with adult disease indicators were not so clear-cut. Increased size at birth and in childhood were positively associated with adult body-mass index and to a lesser extent with blood pressure values, but not with blood glucose concentrations. In our new analyses and in published work, lower birthweight and undernutrition in childhood were risk factors for high glucose concentrations, blood pressure, and harmful lipid profiles once adult body-mass index and height were adjusted for, suggesting that rapid postnatal weight gain--especially after infancy--is linked to these conditions. The review of published works indicates that there is insufficient information about long-term changes in immune function, blood lipids, or osteoporosis indicators. Birthweight is positively associated with lung function and with the incidence of some cancers, and undernutrition could be associated with mental illness. We noted that height-for-age at 2 years was the best predictor of human capital and that undernutrition is associated with lower human capital. We conclude that damage suffered in early life leads to permanent impairment, and might also affect future generations. Its prevention will probably bring about important health, educational, and economic benefits. Chronic diseases are especially common in undernourished children who experience rapid weight gain after infancy.","title":"Maternal and child undernutrition: consequences for adult health and human capital"},{"docid":"24249915","text":"To gain insights into the possible role of oestrogen receptor (ER) beta in breast carcinogenesis, immunohistochemical analysis of ER beta was performed on 512 breast specimens encompassing normal (n = 138), pure ductal carcinoma in situ (n = 16), invasive cancers (n = 319), lymph node metastases (n = 31), and recurrences (n = 8). Real-time polymerase chain reaction (PCR) was used to investigate the methylation status of the ER beta gene in the ER beta negative breast cancer cell lines SkBr3 and MDA-MB-435. A gradual reduction in, but not a complete loss of, ER beta expression was observed during the transition from normal and pre-invasive lesions to invasive cancers, where ER beta was lost in 21% of cases. This was more pronounced in invasive ductal than in lobular carcinomas, a significantly higher proportion of which were ER beta-positive (74% compared with 91%, respectively, p = 0.0004). Examination of paired primary cancers with their axillary lymph node metastases showed that if ER beta was present in the primary tumour, it persisted in the metastasis. Treatment of ER beta-negative cell lines with DNA methyl transferase inhibitors restored ER beta expression, providing experimental evidence that silencing of ER beta in breast carcinomas could be due to promoter hypermethylation. These results suggest that loss of ER beta expression is one of the hallmarks of breast carcinogenesis and that it may be a reversible process involving methylation.","title":"Reduced expression of oestrogen receptor beta in invasive breast cancer and its re-expression using DNA methyl transferase inhibitors in a cell line model."},{"docid":"11360768","text":"OBJECTIVE To evaluate the effects of dietary and lifestyle interventions in pregnancy on maternal and fetal weight and to quantify the effects of these interventions on obstetric outcomes. DESIGN Systematic review and meta-analysis. DATA SOURCES Major databases from inception to January 2012 without language restrictions. STUDY SELECTION Randomised controlled trials that evaluated any dietary or lifestyle interventions with potential to influence maternal weight during pregnancy and outcomes of pregnancy. DATA SYNTHESIS Results summarised as relative risks for dichotomous data and mean differences for continuous data. RESULTS We identified 44 relevant randomised controlled trials (7278 women) evaluating three categories of interventions: diet, physical activity, and a mixed approach. Overall, there was 1.42 kg reduction (95% confidence interval 0.95 to 1.89 kg) in gestational weight gain with any intervention compared with control. With all interventions combined, there were no significant differences in birth weight (mean difference -50 g, -100 to 0 g) and the incidence of large for gestational age (relative risk 0.85, 0.66 to 1.09) or small for gestational age (1.00, 0.78 to 1.28) babies between the groups, though by itself physical activity was associated with reduced birth weight (mean difference -60 g, -120 to -10 g). Interventions were associated with a reduced the risk of pre-eclampsia (0.74, 0.60 to 0.92) and shoulder dystocia (0.39, 0.22 to 0.70), with no significant effect on other critically important outcomes. Dietary intervention resulted in the largest reduction in maternal gestational weight gain (3.84 kg, 2.45 to 5.22 kg), with improved pregnancy outcomes compared with other interventions. The overall evidence rating was low to very low for important outcomes such as pre-eclampsia, gestational diabetes, gestational hypertension, and preterm delivery. CONCLUSIONS Dietary and lifestyle interventions in pregnancy can reduce maternal gestational weight gain and improve outcomes for both mother and baby. Among the interventions, those based on diet are the most effective and are associated with reductions in maternal gestational weight gain and improved obstetric outcomes.","title":"Effects of interventions in pregnancy on maternal weight and obstetric outcomes: meta-analysis of randomised evidence"},{"docid":"26611834","text":"CONTEXT Maternal depressive symptoms during pregnancy have been reported in some, but not all, studies to be associated with an increased risk of preterm birth (PTB), low birth weight (LBW), and intrauterine growth restriction (IUGR). OBJECTIVE To estimate the risk of PTB, LBW, and IUGR associated with antenatal depression. DATA SOURCES AND STUDY SELECTION We searched for English-language and non-English-language articles via the MEDLINE, PsycINFO, CINAHL, Social Work Abstracts, Social Services Abstracts, and Dissertation Abstracts International databases (January 1980 through December 2009). We aimed to include prospective studies reporting data on antenatal depression and at least 1 adverse birth outcome: PTB (<37 weeks' gestation), LBW (<2500 g), or IUGR (<10th percentile for gestational age). Of 862 reviewed studies, 29 US-published and non-US-published studies met the selection criteria. DATA EXTRACTION Information was extracted on study characteristics, antenatal depression measurement, and other biopsychosocial risk factors and was reviewed twice to minimize error. DATA SYNTHESIS Pooled relative risks (RRs) for the effect of antenatal depression on each birth outcome were calculated using random-effects methods. In studies of PTB, LBW, and IUGR that used a categorical depression measure, pooled effect sizes were significantly larger (pooled RR [95% confidence interval] = 1.39 [1.19-1.61], 1.49 [1.25-1.77], and 1.45 [1.05-2.02], respectively) compared with studies that used a continuous depression measure (1.03 [1.00-1.06], 1.04 [0.99-1.09], and 1.02 [1.00-1.04], respectively). The estimates of risk for categorically defined antenatal depression and PTB and LBW remained significant when the trim-and-fill procedure was used to correct for publication bias. The risk of LBW associated with antenatal depression was significantly larger in developing countries (RR = 2.05; 95% confidence interval, 1.43-2.93) compared with the United States (RR = 1.10; 95% confidence interval, 1.01-1.21) or European social democracies (RR = 1.16; 95% confidence interval, 0.92-1.47). Categorically defined antenatal depression tended to be associated with an increased risk of PTB among women of lower socioeconomic status in the United States. CONCLUSIONS Women with depression during pregnancy are at increased risk for PTB and LBW, although the magnitude of the effect varies as a function of depression measurement, country location, and US socioeconomic status. An important implication of these findings is that antenatal depression should be identified through universal screening and treated.","title":"A meta-analysis of depression during pregnancy and the risk of preterm birth, low birth weight, and intrauterine growth restriction."},{"docid":"12438901","text":"BACKGROUND For women with oestrogen receptor (ER)-positive early breast cancer, treatment with tamoxifen for 5 years substantially reduces the breast cancer mortality rate throughout the first 15 years after diagnosis. We aimed to assess the further effects of continuing tamoxifen to 10 years instead of stopping at 5 years. METHODS In the worldwide Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) trial, 12,894 women with early breast cancer who had completed 5 years of treatment with tamoxifen were randomly allocated to continue tamoxifen to 10 years or stop at 5 years (open control). Allocation (1:1) was by central computer, using minimisation. After entry (between 1996 and 2005), yearly follow-up forms recorded any recurrence, second cancer, hospital admission, or death. We report effects on breast cancer outcomes among the 6846 women with ER-positive disease, and side-effects among all women (with positive, negative, or unknown ER status). Long-term follow-up still continues. This study is registered, number ISRCTN19652633. FINDINGS Among women with ER-positive disease, allocation to continue tamoxifen reduced the risk of breast cancer recurrence (617 recurrences in 3428 women allocated to continue vs 711 in 3418 controls, p=0·002), reduced breast cancer mortality (331 deaths vs 397 deaths, p=0·01), and reduced overall mortality (639 deaths vs 722 deaths, p=0·01). The reductions in adverse breast cancer outcomes appeared to be less extreme before than after year 10 (recurrence rate ratio [RR] 0·90 [95% CI 0·79–1·02] during years 5–9 and 0·75 [0·62–0·90] in later years; breast cancer mortality RR 0·97 [0·79–1·18] during years 5–9 and 0·71 [0·58–0·88] in later years). The cumulative risk of recurrence during years 5–14 was 21·4% for women allocated to continue versus 25·1% for controls; breast cancer mortality during years 5–14 was 12·2% for women allocated to continue versus 15·0% for controls (absolute mortality reduction 2·8%). Treatment allocation seemed to have no effect on breast cancer outcome among 1248 women with ER-negative disease, and an intermediate effect among 4800 women with unknown ER status. Among all 12,894 women, mortality without recurrence from causes other than breast cancer was little affected (691 deaths without recurrence in 6454 women allocated to continue versus 679 deaths in 6440 controls; RR 0·99 [0·89–1·10]; p=0·84). For the incidence (hospitalisation or death) rates of specific diseases, RRs were as follows: pulmonary embolus 1·87 (95% CI 1·13–3·07, p=0·01 [including 0·2% mortality in both treatment groups]), stroke 1·06 (0·83–1·36), ischaemic heart disease 0·76 (0·60–0·95, p=0·02), and endometrial cancer 1·74 (1·30–2·34, p=0·0002). The cumulative risk of endometrial cancer during years 5–14 was 3·1% (mortality 0·4%) for women allocated to continue versus 1·6% (mortality 0·2%) for controls (absolute mortality increase 0·2%). INTERPRETATION For women with ER-positive disease, continuing tamoxifen to 10 years rather than stopping at 5 years produces a further reduction in recurrence and mortality, particularly after year 10. These results, taken together with results from previous trials of 5 years of tamoxifen treatment versus none, suggest that 10 years of tamoxifen treatment can approximately halve breast cancer mortality during the second decade after diagnosis. FUNDING Cancer Research UK, UK Medical Research Council, AstraZeneca UK, US Army, EU-Biomed.","title":"Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial"},{"docid":"16086778","text":"The biological antagonism between Notch and Numb controls the proliferative/differentiative balance in development and homeostasis. Although altered Notch signaling has been linked to human diseases, including cancer, evidence for a substantial involvement of Notch in human tumors has remained elusive. Here, we show that Numb-mediated control on Notch signaling is lost in ∼50% of human mammary carcinomas, due to specific Numb ubiquitination and proteasomal degradation. Mechanistically, Numb operates as an oncosuppressor, as its ectopic expression in Numb-negative, but not in Numb-positive, tumor cells inhibits proliferation. Increased Notch signaling is observed in Numb-negative tumors, but reverts to basal levels after enforced expression of Numb. Conversely, Numb silencing increases Notch signaling in normal breast cells and in Numb-positive breast tumors. Finally, growth suppression of Numb-negative, but not Numb-positive, breast tumors can be achieved by pharmacological inhibition of Notch. Thus, the Numb/Notch biological antagonism is relevant to the homeostasis of the normal mammary parenchyma and its subversion contributes to human mammary carcinogenesis.","title":"Loss of negative regulation by Numb over Notch is relevant to human breast carcinogenesis"},{"docid":"36432234","text":"Wedelolactone, a plant coumestan, was shown to act as anti-cancer agent for breast and prostate carcinomas in vitro and in vivo targeting multiple cellular proteins including androgen receptors, 5-lipoxygenase and topoisomerase IIα. It is cytotoxic to breast, prostate, pituitary and myeloma cancer cell lines in vitro at μM concentrations. In this study, however, a novel biological activity of nM dose of wedelolactone was demonstrated. Wedelolactone acts as agonist of estrogen receptors (ER) α and β as demonstrated by transactivation of estrogen response element (ERE) in cells transiently expressing either ERα or ERβ and by molecular docking of this coumestan into ligand binding pocket of both ERα and ERβ. In breast cancer cells, wedelolactone stimulates growth of estrogen receptor-positive cells, expression of estrogen-responsive genes and activates rapid non-genomic estrogen signalling. All these effects can be inhibited by pretreatment with pure ER antagonist ICI 182,780 and they are not observed in ER-negative breast cancer cells. We conclude that wedelolactone acts as phytoestrogen in breast cancer cells by stimulating ER genomic and non-genomic signalling pathways.","title":"Wedelolactone induces growth of breast cancer cells by stimulation of estrogen receptor signalling."},{"docid":"30786800","text":"BACKGROUND The International Lipid-Based Nutrient Supplements Project developed a small-quantity (20 g/d) lipid-based nutrient supplement (LNS) for pregnant and lactating women. OBJECTIVE We evaluated the effects of prenatal LNS supplementation on fetal growth. DESIGN In a community-based, partially double-blind, individually randomized controlled trial, 1320 women ≤20 wk pregnant received 60 mg Fe/400 μg folic acid (IFA), or 1-2 Recommended Dietary Allowances of 18 micronutrients, including 20 mg Fe (MMN), or LNS with the same micronutrients as the MMN group, plus 4 minerals and macronutrients contributing 118 kcal (LNS) daily until delivery. Fetal growth was compared across groups by using intention-to-treat analysis. The primary outcome was birth length. RESULTS This analysis included 1057 women (IFA = 349, MMN = 354, LNS = 354). Groups did not differ significantly in mean birth length, length-for-age z score (LAZ), head circumference, or percentage low birth length but differed in mean birth weight (P = 0.044), weight-for-age z score (WAZ; P = 0.046), and BMI-for-age z score (BMIZ; P = 0.040), with a trend toward differences in low birth weight (P = 0.069). In pairwise comparisons, the LNS group had greater mean birth weight (+85 g; P = 0.040), WAZ (+0.19; P = 0.045), and BMIZ (+0.21; P = 0.035) and a lower risk of low birth weight (RR: 0.61, 95% CI: 0.39, 0.96; P = 0.032) than did the IFA group. The other group differences were not significant. The effect of intervention was modified by mother's parity, age, height, baseline hemoglobin, household food insecurity, and child sex, with parity being the most consistent modifier. Among primiparous women (IFA = 131; MMN = 110; LNS = 128), the LNS group had greater mean birth length (+0.91 cm; P = 0.001), LAZ (+0.47; P = 0.001), weight (+237 g; P < 0.001), WAZ (+0.56; P < 0.001), BMIZ (+0.52; P < 0.001), head circumference (0.50 cm; P = 0.017), and head circumference-for-age z score (+0.40; P = 0.022) than did the IFA group; similar differences were found when comparing the LNS and MMN groups among primiparous women, and no group differences were found among multiparous women. CONCLUSION Prenatal LNS supplementation can improve fetal growth among vulnerable women in Ghana, particularly primiparous women. This trial was registered at clinicaltrials.gov as NCT00970866.","title":"Lipid-based nutrient supplement increases the birth size of infants of primiparous women in Ghana."}],"string":"[\n {\n \"docid\": \"37480103\",\n \"text\": \"CONTEXT During pregnancy, serum levels of estrogen, progesterone, and other hormones are markedly higher than during other periods of life. Pregnancy hormones primarily are produced in the placenta, and signs of placental impairment may serve as indirect markers of hormone exposures during pregnancy. During pregnancy, these markers have been inconsistently associated with subsequent risk of breast cancer in the mother. OBJECTIVE To examine associations between indirect markers of hormonal exposures, such as placental weight and other pregnancy characteristics, and maternal risk of developing breast cancer. DESIGN AND SETTING Population-based cohort study using data from the Swedish Birth Register, the Swedish Cancer Register, the Swedish Cause of Death Register, and the Swedish Register of Population and Population Changes. PARTICIPANTS Women included in the Sweden Birth Register who delivered singletons between 1982 and 1989, with complete information on date of birth and gestational age. Women were followed up until the occurrence of breast cancer, death, or end of follow-up (December 31, 2001). Cox proportional hazards models were used to estimate associations between hormone exposures and risks of breast cancer. MAIN OUTCOME MEASURE Incidence of invasive breast cancer. RESULTS Of 314,019 women in the cohort, 2216 (0.7%) developed breast cancer during the follow-up through 2001, of whom 2100 (95%) were diagnosed before age 50 years. Compared with women who had placentas weighing less than 500 g in 2 consecutive pregnancies, the risk of breast cancer was increased among women whose placentas weighed between 500 and 699 g in their first pregnancy and at least 700 g in their second pregnancy (or vice versa) (adjusted hazard ratio, 1.82; 95% confidence interval [CI], 1.07-3.08), and the corresponding risk was doubled among women whose placentas weighed at least 700 g in both pregnancies (adjusted hazard ratio, 2.05; 95% CI, 1.15-3.64). A high birth weight (> or =4000 g) in 2 successive births was associated with an increased risk of breast cancer before but not after adjusting for placental weight and other covariates (adjusted hazard ratio, 1.10; 95% CI, 0.76-1.59). CONCLUSIONS Placental weight is positively associated with maternal risk of breast cancer. These results further support the hypothesis that pregnancy hormones are important modifiers of subsequent maternal breast cancer risk.\",\n \"title\": \"Pregnancy characteristics and maternal risk of breast cancer.\"\n },\n {\n \"docid\": \"5487448\",\n \"text\": \"Birth weight is a significant predictor of breast cancer risk in adult life and mammary gland mass could be an intermediate stage in this long process. We have studied the association of birth size measurements with mammographic density, a marker of mammary gland mass. For a population-based sample of 893 postmenopausal women without previous cancer in Sweden, we retrieved information on birth size from birth records and their most recent mammography. Film mammograms of the medio-lateral oblique view were digitized and the Cumulus software was used for computer-assisted semi-automated thresholding of mammographic density. Results were analyzed using generalized linear models controlling for possible confounders. Mean percent mammographic density increased when comparing the extreme categories of birth weight (from 15.6% to 18.6%) and head circumference (from 15.5% to 20.4%), and the corresponding linear trends were statistically significant (p values 0.02 and 0.007, respectively). The associations were particularly strong when the cutoff for high versus low mammographic density was set at the relatively high value of 50%. Compared to women weighing 3001-3500 grams at birth, women with birth weights >4000g were at almost 3-fold risk of developing high mammographic density (odds ratio: 2.9, 95% confidence interval 1.1 to 7.9). No association with mammographic density was evident with respect to birth length which, however, is known to be less accurately measured. These results indicate that adult breast density, a powerful predictor of breast cancer risk, has intrauterine roots, as reflected in birth size.\",\n \"title\": \"Birth weight and mammographic density among postmenopausal women in Sweden.\"\n },\n {\n \"docid\": \"38784540\",\n \"text\": \"Objective To determine whether risk factors in childhood and early adulthood affect later mammographic breast density. Methods: Subjects were 628 women who attended a medical examination at the University of Glasgow Student Health Service (1948–1968), responded to a questionnaire (2001) and had a screening mammogram in Scotland (1989–2002). Mammograms (median age of 59years) were classified using a six category classification (SCC) of breast density percent. Logistic regression was used to determine associations between risk factors and having a high-risk mammogram (≥25 dense). Results: In multi-variable analyses, high-risk mammograms were associated with parity (adjusted odds ratio (OR) per child: 0.77 (95 confidence interval (CI) 0.61–0.99)), age at first birth, OR per year: 1.05 (0.99–1.11), smoking at university, OR smokers versus non-smokers: 0.58 (0.36–0.92) and body mass index (BMI) while at university, OR per 1kg/m20.75 (0.69–0.82). No associations with SCC were found for age at menarche, birth weight, oral contraceptive (OC) use, height, leg length or exercise at age 20. Conclusions: We confirm previous findings that breast density is affected by reproductive events and some anthropometric measures, however most of the risk factors acting throughout the life course which we examined were not closely related to adult breast density.\",\n \"title\": \"Life course breast cancer risk factors and adult breast density (United Kingdom)\"\n },\n {\n \"docid\": \"22007333\",\n \"text\": \"Menstrual and reproductive factors may increase breast cancer risk through a pathway that includes increased mammographic density. We assessed whether known or suspected menstrual and reproductive breast cancer risk factors were cross-sectionally associated with mammographic density, by measuring area of radiographic density and total breast area on mammograms from 801 participants in the Study of Women’s Health Across the Nation (SWAN), a multi-ethnic cohort of pre- and early perimenopausal women. From multivariable linear regression, the following menstrual or reproductive factors were independently associated with percent mammographic density (area of dense breast/breast area): older age at menarche (β = 10.3, P < 0.01, for >13 vs. <12 years), premenstrual cravings and bloating (β = −3.36, P = 0.02), younger age at first full-term birth (β = −8.12, P < 0.01 for ≤23 years versus no births), greater number of births (β = −6.80, P < 0.01 for ≥3 births versus no births), and premenopausal status (β = 3.78, P < 0.01 versus early perimenopausal). Only number of births remained associated with percent density after adjustment for age, race/ethnicity, study site, body mass index (BMI), and smoking. In addition, stratified analyses revealed that the association with number of births was confined to women within the lowest BMI tertile (β = −12.2, P < 0.01 for ≥3 births versus no births). Our data support a mechanism for parity and breast cancer that involves mammographic density among pre- and early perimenopausal women that may be modified by body size.\",\n \"title\": \"Menstrual and reproductive factors in relation to mammographic density: the Study of Women’s Health Across the Nation (SWAN)\"\n },\n {\n \"docid\": \"13765757\",\n \"text\": \"Ages at menarche and first birth are established risk factors for breast cancer. The interval between these ages may also affect risk, since the breast is more susceptible to carcinogenic insults during this period than during the parous period. However, few investigators have studied this relation. Using logistic regression, the authors evaluated associations between the timing of reproductive events and breast cancer risk among 4,013 cases and 4,069 controls enrolled in a multicenter, population-based US case-control study of White and African-American women (1994-1998). For White, parous premenopausal and postmenopausal women, those who had an interval of > or =16 years between the ages of menarche and first birth had 1.5-fold (95% confidence interval (CI): 1.0, 2.2) and 1.4-fold (95% CI: 1.1, 1.8) increased risks of breast cancer, respectively, in comparison with those who had < or =5 years between these ages. Adjusting for age at first birth altered these risk estimates somewhat, to odds ratios of 1.5 (95% CI: 0.8, 2.9) and 1.0 (95% CI: 0.6, 1.5), respectively. These associations were stronger for lobular and hormone-receptor-positive tumors but were absent among premenopausal African-American women. The authors conclude that the interval between age at menarche and age at first birth is associated with the risk of hormonally sensitive types of breast cancer, particularly among White women.\",\n \"title\": \"Timing of menarche and first full-term birth in relation to breast cancer risk.\"\n },\n {\n \"docid\": \"16098747\",\n \"text\": \"Evaluate known breast cancer risk factors in relation to breast density. We examined factors in relation to breast density in 144,018 New Hampshire (NH) women with at least one mammogram recorded in a statewide mammography registry. Mammographic breast density was measured by radiologists using the BI-RADS classification; risk factors of interest were obtained from patient intake forms and questionnaires. Initial analyses showed a strong inverse influence of age and body mass index (BMI) on breast density. In addition, women with late age at menarche, late age at first birth, premenopausal women, and those currently using hormone therapy (HT) tended to have higher breast density, while those with greater parity tended to have less dense breasts. Analyses stratified on age and BMI suggested interactions, which were formally assessed in a multivariable model. The impact of current HT use, relative to nonuse, differed across age groups, with an inverse association in younger women, and a positive association in older women (p < 0.0001 for the interaction). The positive effects of age at menarche and age at first birth, and the inverse influence of parity were less apparent in women with low BMI than in those with high BMI (p = 0.04, p < 0.0001 and p = 0.01, respectively, for the interactions). We also noted stronger positive effects for age at first birth in postmenopausal women (p = 0.004 for the interaction). The multivariable model indicated a slight positive influence of family history of breast cancer. The influence of age at menarche and reproductive factors on breast density is less evident in women with high BMI. Density is reduced in young women using HT, but increased in HT users of age 50 or more.\",\n \"title\": \"Breast cancer risk factors in relation to breast density (United States)\"\n },\n {\n \"docid\": \"13831842\",\n \"text\": \"The association between anthropometric indices and the risk of breast cancer was analyzed using pooled data from seven prospective cohort studies. Together, these cohorts comprise 337,819 women and 4,385 incident invasive breast cancer cases. In multivariate analyses controlling for reproductive, dietary, and other risk factors, the pooled relative risk (RR) of breast cancer per height increment of 5 cm was 1.02 (95% confidence interval (CI): 0.96, 1.10) in premenopausal women and 1.07 (95% CI: 1.03, 1.12) in postmenopausal women. Body mass index (BMI) showed significant inverse and positive associations with breast cancer among pre- and postmenopausal women, respectively; these associations were nonlinear. Compared with premenopausal women with a BMI of less than 21 kg/m2, women with a BMI exceeding 31 kg/m2 had an RR of 0.54 (95% CI: 0.34, 0.85). In postmenopausal women, the RRs did not increase further when BMI exceeded 28 kg/m2; the RR for these women was 1.26 (95% CI: 1.09, 1.46). The authors found little evidence for interaction with other breast cancer risk factors. Their data indicate that height is an independent risk factor for postmenopausal breast cancer; in premenopausal women, this relation is less clear. The association between BMI and breast cancer varies by menopausal status. Weight control may reduce the risk among postmenopausal women.\",\n \"title\": \"Pooled analysis of prospective cohort studies on height, weight, and breast cancer risk.\"\n },\n {\n \"docid\": \"3285322\",\n \"text\": \"PURPOSE Mutations in the BRCA1 and BRCA2 genes confer greater risk of developing breast cancer. We determined whether tumor pathologic features and clinical features differ in patients with and without BRCA mutations. PATIENTS AND METHODS Tumor pathologic features and clinical characteristics were examined in 491 women with breast cancer who underwent genetic testing for BRCA mutations between 1997 and 2006. A retrospective review of medical records was conducted to determine clinical characteristics including ethnicity, age and clinical stage at diagnosis, age at parity, number of full-term pregnancies, use of oral contraceptives and hormone replacement therapy, and BRCA mutation status. Tumor pathology was reviewed to determine histologic type, tumor grade, and estrogen receptor, progesterone receptor, and HER-2/neu status. RESULTS Of the 491 patients with identified breast cancers, 391 patients were BRCA negative, and 86 patients were BRCA positive. Triple-negative breast cancer (ie, those with negative estrogen receptor, progesterone receptor, and HER-2/neu status) was diagnosed in 57.1% of the BRCA1-positive patients, 23.3% of the BRCA2-positive patients, and 13.8% of the BRCA-negative patients. BRCA1 mutation carriers had higher nuclear grade tumors than the other two groups (P < .001). Of the triple-negative cancer patients, BRCA2 mutation carriers were older when diagnosed than BRCA1 mutation carriers and noncarriers (P < .01). CONCLUSION These results suggest that tumors associated with BRCA1 mutations may be divided into two distinct groups, triple-negative and non-triple-negative groups. Future studies should seek to determine whether patients with BRCA1 mutations and triple-negative breast cancer respond to treatment better than BRCA-negative patients with similar tumor pathology.\",\n \"title\": \"Clinical and pathologic characteristics of patients with BRCA-positive and BRCA-negative breast cancer.\"\n },\n {\n \"docid\": \"13831558\",\n \"text\": \"BACKGROUND Extensive mammographic density is associated with an increased risk of breast cancer and makes the detection of cancer by mammography difficult, but the influence of density on risk according to method of cancer detection is unknown. METHODS We carried out three nested case-control studies in screened populations with 1112 matched case-control pairs. We examined the association of the measured percentage of density in the baseline mammogram with risk of breast cancer, according to method of cancer detection, time since the initiation of screening, and age. RESULTS As compared with women with density in less than 10% of the mammogram, women with density in 75% or more had an increased risk of breast cancer (odds ratio, 4.7; 95% confidence interval [CI], 3.0 to 7.4), whether detected by screening (odds ratio, 3.5; 95% CI, 2.0 to 6.2) or less than 12 months after a negative screening examination (odds ratio, 17.8; 95% CI, 4.8 to 65.9). Increased risk of breast cancer, whether detected by screening or other means, persisted for at least 8 years after study entry and was greater in younger than in older women. For women younger than the median age of 56 years, 26% of all breast cancers and 50% of cancers detected less than 12 months after a negative screening test were attributable to density in 50% or more of the mammogram. CONCLUSIONS Extensive mammographic density is strongly associated with the risk of breast cancer detected by screening or between screening tests. A substantial fraction of breast cancers can be attributed to this risk factor.\",\n \"title\": \"Mammographic density and the risk and detection of breast cancer.\"\n },\n {\n \"docid\": \"313403\",\n \"text\": \"The tumor microenvironment is composed of tumor cells, fibroblasts, endothelial cells and infiltrating immune cells, which may inhibit or promote tumor growth and progression. The objectives of this retrospective study were to characterize the density of tumor-associated macrophages (TAMs) in breast cancer, and to correlate the density of TAMs with clinicopathological parameters. Paraffin-embedded specimens and clinicopathological data, including up to 5 years follow-up information, were obtained from 172 breast cancer patients. Immunohistochemical staining for CD68 (marker for macrophages) was performed and evaluated in a blinded fashion. We found that TAMs were significantly frequent in high histopathological grade breast cancer patients. Breast cancer patients with a high density of TAMs had significantly lower rates of disease-free survival and 5-year overall survival than patients with low density of TAMs. Furthermore, high-infiltration of TAMs indicated worse survival rate for patients with node-negative breast cancer. In conclusion, the number of TAMs in the tumor stroma is an independent predictor of survival time for breast cancer patients. High-infiltration of TAMs is a significant unfavorable prognostic factor for patients with invasive breast cancer and, as such, is a potentially useful prognostic marker for breast cancer.\",\n \"title\": \"High-Infiltration of Tumor-Associated Macrophages Predicts Unfavorable Clinical Outcome for Node-Negative Breast Cancer\"\n },\n {\n \"docid\": \"25973484\",\n \"text\": \"Obesity has a complicated relationship to both breast cancer risk and the clinical behavior of the established disease. In postmenopausal women, particularly the elderly, various measures of obesity have been positively associated with risk. However, before menopause increased body weight is inversely related to breast cancer risk. In both premenopausal and postmenopausal breast cancer, the mechanisms by which body weight and obesity affect risk have been related to estrogenic activity. Obesity has also been related to advanced disease at diagnosis and with a poor prognosis in both premenopausal and postmenopausal breast cancer. Breast cancer in African-American women, considering its relationship to obesity, exhibits some important differences from those described in white women, although the high prevalence of obesity in African-American women may contribute to the relatively poor prognosis compared with white American women. Despite the emphasis on estrogens to explain the effects of obesity on breast cancer, other factors may prove to be equally or more important, particularly as they relate to expression of an aggressive tumor phenotype. Among these, this review serves to stress insulin, insulin-like growth factor-I, and leptin, and their relationship to angiogenesis, and transcriptional factors.\",\n \"title\": \"Breast cancer and obesity: an update.\"\n },\n {\n \"docid\": \"1171121\",\n \"text\": \"A considerable subgroup of patients with early breast cancer does not address benefits of anthracycline based chemotherapy. The aim of this retrospective study was to investigate the effect of microvessel density (MVD) and status of p53 protein on 5-year disease free survival (DFS) in the group of breast cancer patients treated with anthracyclines in adjuvant setting. Correlations between MVD, p53 status and other clinicopathological parameters were also assessed. MVD and p53 status were analyzed immunohistochemically in the group of 172 women with breast cancer in clinical stage T1-2, N1-N2, M0. There were 123 tumors (71.5 %) with lower MVD (≤ 214.8 microvesells/mm(2)) and 49 (28.5 %) with higher MVD (>214.8 microvesells/mm(2)). The proportion of higher MVD tumors significantly increased in N2 (P = 0.000) and in estrogen (P = 0.046) or progesterone receptors (P = 0.029) negative tumors. p53 positivity was indicated in 50 cancers (29.1 %) and was significantly associated with higher grade (P = 0.000), steroid receptors negativity (P = 0.000), cytokeratin5/6 positivity (P = 0.026), topoisomerase IIα overexpression (P = 0.005) and higher proliferation rate (P = 0.001). In univariate analysis, higher MVD (P = 0.016) and p53 negativity (P = 0.023) were significantly related with longer DFS (median follow-up 36 months). In multivariate Cox regression analysis MVD was independently associated with DFS. These data suggest that higher MVD is favourable prognostic factors for early advanced breast cancer patients after adjuvant anthracycline based chemotherapy.\",\n \"title\": \"Microvessel Density and Status of p53 Protein as Potential Prognostic Factors for Adjuvant Anthracycline Chemotherapy in Retrospective Analysis of Early Breast Cancer Patients Group\"\n },\n {\n \"docid\": \"20280410\",\n \"text\": \"Inherited mutations in the gene BRCA2 predispose carriers to early onset breast cancer, but such mutations account for fewer than 2% of all cases in East Anglia. It is likely that low penetrance alleles explain the greater part of inherited susceptibility to breast cancer; polymorphic variants in strongly predisposing genes, such as BRCA2, are candidates for this role. BRCA2 is thought to be involved in DNA double strand break-repair. Few mice in which Brca2 is truncated survive to birth; of those that do, most are male, smaller than their normal littermates and have high cancer incidence. Here we show that a common human polymorphism (N372H) in exon 10 of BRCA2 confers an increased risk of breast cancer: the HH homozygotes have a 1.31-fold (95% CI, 1.07–1.61) greater risk than the NN group. Moreover, in normal female controls of all ages there is a significant deficiency of homozygotes compared with that expected from Hardy-Weinberg equilibrium, whereas in males there is an excess of homozygotes: the HH group has an estimated fitness of 0.82 in females and 1.38 in males. Therefore, this variant of BRCA2 appears also to affect fetal survival in a sex-dependent manner.\",\n \"title\": \"A common variant in BRCA2 is associated with both breast cancer risk and prenatal viability\"\n },\n {\n \"docid\": \"5222182\",\n \"text\": \"Understanding which factors influence mammographically dense and nondense areas is important because percent mammographic density adjusted for age is a strong, continuously distributed risk factor for breast cancer, especially when adjusted for weight or body mass index. Using computer-assisted methods, we measured mammographically dense areas for 571 monozygotic and 380 dizygotic Australian and North American twin pairs ages 40 to 70 years. We used a novel regression modeling approach in which each twin's measure of dense and nondense area was regressed against one or both of the twin's and co-twin's covariates. The nature of changes to regression estimates with the inclusion of the twin and/or co-twin's covariates can be evaluated for consistency with causal and/or other models. By causal, we mean that if it were possible to vary a covariate experimentally then the expected value of the outcome measure would change. After adjusting for the individual's weight, the co-twin associations with weight were attenuated, consistent with a causal effect of weight on mammographic measures, which in absolute log cm(2)/kg was thrice stronger for nondense than dense area. After adjusting for weight, later age at menarche, and greater height were associated with greater dense and lesser nondense areas in a manner inconsistent with causality. The associations of dense and nondense areas with parity are consistent with a causal effect and/or within-person confounding. The associations between mammographic density measures and height are consistent with shared early life environmental factors that predispose to both height and percent mammographic density and possibly breast cancer risk.\",\n \"title\": \"Predictors of mammographic density: insights gained from a novel regression analysis of a twin study.\"\n },\n {\n \"docid\": \"16701509\",\n \"text\": \"BACKGROUND The prevalence of metabolic syndrome (obesity, glucose intolerance, low serum high-density lipoprotein cholesterol [HDL-C], high serum triglycerides, hypertension) is high and increasing in parallel with an increasing breast cancer incidence worldwide. HDL-C represents an important aspect of the syndrome, yet its role in breast cancer is still undefined. METHODS In two population-based screening surveys during 1977-1983 and 1985-1987, serum HDL-C was assayed enzymatically among 38,823 Norwegian women aged 17-54 years at entry. Height, weight, blood pressure, serum lipids, fat and energy intake, physical activity, parity, oral contraceptive use, hormone therapy use, alcohol intake, and tobacco use were also assessed. We used Cox proportional hazards modeling to estimate the relative risk (RR) of breast cancer associated with serum HDL-C levels and to adjust for potential confounding variables. We performed stratified analyses to evaluate effect modification by body mass index (BMI) and menopausal status. All statistical tests were two-sided. RESULTS During a median follow-up of 17.2 years, we identified 708 cases of invasive breast cancer. In multivariable analysis, the risk of postmenopausal breast cancer was inversely related to quartile of HDL-C (P(trend) =.02). Among women with HDL-C above 1.64 mmol/L (highest quartile) versus below 1.20 mmol/L (lowest quartile), the relative risk was 0.75 (95% confidence interval [CI] = 0.58 to 0.97). The HDL-C association was confined to women in the heavier subgroup (BMI > or =25 kg/m2), for whom the relative risk of postmenopausal breast cancer in those with HDL-C above 1.64 mmol/L versus below 1.20 mmol/L was 0.43 (95% CI = 0.28 to 0.67; P(trend)<.001; P(interaction) =.001). CONCLUSION Low HDL-C, as part of the metabolic syndrome, is associated with increased postmenopausal breast cancer risk.\",\n \"title\": \"Serum high-density lipoprotein cholesterol, metabolic profile, and breast cancer risk.\"\n },\n {\n \"docid\": \"18340282\",\n \"text\": \"BACKGROUND Information is scarce about the combined effects on breast cancer incidence of low-penetrance genetic susceptibility polymorphisms and environmental factors (reproductive, behavioural, and anthropometric risk factors for breast cancer). To test for evidence of gene-environment interactions, we compared genotypic relative risks for breast cancer across the other risk factors in a large UK prospective study. METHODS We tested gene-environment interactions in 7610 women who developed breast cancer and 10 196 controls without the disease, studying the effects of 12 polymorphisms (FGFR2-rs2981582, TNRC9-rs3803662, 2q35-rs13387042, MAP3K1-rs889312, 8q24-rs13281615, 2p-rs4666451, 5p12-rs981782, CASP8-rs1045485, LSP1-rs3817198, 5q-rs30099, TGFB1-rs1982073, and ATM-rs1800054) in relation to prospectively collected information about ten established environmental risk factors (age at menarche, parity, age at first birth, breastfeeding, menopausal status, age at menopause, use of hormone replacement therapy, body-mass index, height, and alcohol consumption). FINDINGS After allowance for multiple testing none of the 120 comparisons yielded significant evidence of a gene-environment interaction. By contrast with previous suggestions, there was little evidence that the genotypic relative risks were affected by use of hormone replacement therapy, either overall or for oestrogen-receptor-positive disease. Only one of the 12 polymorphisms was correlated with any of the ten other risk factors: carriers of the high-risk C allele of MAP3K1-rs889312 were significantly shorter than non-carriers (mean height 162.4 cm [95% CI 162.1-162.7] vs 163.1 cm [162.9-163.2]; p=0.01 after allowance for multiple testing). INTERPRETATION Risks of breast cancer associated with low-penetrance susceptibility polymorphisms do not vary significantly with these ten established environmental risk factors. FUNDING Cancer Research UK and the UK Medical Research Council.\",\n \"title\": \"Gene–environment interactions in 7610 women with breast cancer: prospective evidence from the Million Women Study\"\n },\n {\n \"docid\": \"27240667\",\n \"text\": \"PURPOSE Since 1990, overall breast cancer mortality rates in the United States decreased 24%. This decline has been attributed to mammography screening and adjuvant systemic therapy. However, the efficacy of these modalities may depend on estrogen receptor (ER) expression and age. We therefore examined breast cancer mortality trends in the United States according to ER status and age. METHODS Using the Surveillance, Epidemiology, and End Results (SEER) program (1990-2003), we calculated trends in incidence-based mortality (IBM), annual hazard rates for breast cancer deaths after diagnosis, and relative hazard rates for women with ER-positive and ER-negative tumors. Relative hazard rates were assessed with Cox proportional hazards models, adjusted for stage and grade, and stratified by age at diagnosis. RESULTS During the study period, IBM and annual hazard rates for breast cancer deaths decreased among women with ER-positive and ER-negative tumors, although declines were greater for those with ER-positive tumors. Among women younger than 70 years, relative hazard rates declined 38% for those with ER-positive tumors versus 19% for those with ER-negative tumors. Among women 70 years or older, relative hazard rates declined 14% for those with ER-positive tumors versus no significant decline for those with ER-negative tumors. CONCLUSION In the United States, breast cancer mortality rates have declined among women with ER-positive and ER-negative tumors, with greater declines among younger women and those with ER-positive tumors. Although mortality in all groups remains unacceptably high, additional emphasis should be placed on improving outcomes of breast cancer patients older than 70 years and those of all ages with ER-negative tumors.\",\n \"title\": \"Breast cancer mortality trends in the United States according to estrogen receptor status and age at diagnosis.\"\n },\n {\n \"docid\": \"12762485\",\n \"text\": \"AIM Several studies have investigated the expression of the cytokeratins (CKs), vimentin, the epithelial growth factor receptor (EGFR), the oestrogen receptor (ER), and the progesterone receptor (PgR), in breast cancer, but no study has directly compared p53 mutations with these phenotypic and differentiation markers in the same case. The present study was designed to provide some of this information. METHODS The expression of the p53 and bcl-2 proteins was evaluated by immunohistochemistry in relation to phenotypic characteristics and cellular kinetic parameters (mitotic index and apoptotic index) in 37 cases of ductal carcinoma in situ (DCIS) and 27 cases of infiltrating ductal carcinoma (IDC) of the breast. In addition, p53 gene mutation was examined by polymerase chain reaction single strand conformation polymorphism analysis (SSCP). RESULTS Thirteen cases (eight DCIS and five IDC) showed expression of CK8, CK14, CK18, vimentin, and EGFR, consistent with a stem cell phenotype, whereas 44 cases (27 DCIS and 17 IDC) showed expression of CK8 and CK1, weak or negative expression of CK18, but were negative for vimentin and EGFR, consistent with a luminal cell phenotype. DCIS and IDC cases with a stem cell phenotype were ER/PgR negative and intermediately or poorly differentiated. In contrast, the cases with luminal cell phenotype were ER/PgR positive and well or intermediately differentiated. In addition, intermediately or poorly differentiated cases with a stem cell phenotype showed higher proliferative activity (per cent of MIB-l positive cells) than did intermediately or well differentiated cases with a luminal cell phenotype. Both DCIS and IDC cases with a stem cell phenotype were p53 positive and bcl-2 negative by immunohistochemistry. In IDC, p53 expression was associated with a reduction of both mitotic index and apoptotic index compared with DCIS. Most of the tumours showing a more differentiated phenotype (luminal) were p53 negative and bcl-2 positive. In these cases, cell kinetic parameters increased from DCIS to IDC. These data suggest the existence of subsets of DCIS and IDC that, because of their phenotypic characteristics, could be derived from subpopulations of normal breast cells having different control mechanisms of cell proliferation and neoplastic progression. CONCLUSIONS These results are compatible with the hypothesis that the phenotype of the cell of origin constrains both tumour phenotype and the choice of genetic events; however, the occurrence of p53 mutants by chance during neoplastic transformation cannot be excluded.\",\n \"title\": \"p53 mutation in breast cancer. Correlation with cell kinetics and cell of origin.\"\n },\n {\n \"docid\": \"4828631\",\n \"text\": \"BACKGROUND High body-mass index (BMI) predisposes to several site-specific cancers, but a large-scale systematic and detailed characterisation of patterns of risk across all common cancers adjusted for potential confounders has not previously been undertaken. We aimed to investigate the links between BMI and the most common site-specific cancers. METHODS With primary care data from individuals in the Clinical Practice Research Datalink with BMI data, we fitted Cox models to investigate associations between BMI and 22 of the most common cancers, adjusting for potential confounders. We fitted linear then non-linear (spline) models; investigated effect modification by sex, menopausal status, smoking, and age; and calculated population effects. FINDINGS 5·24 million individuals were included; 166,955 developed cancers of interest. BMI was associated with 17 of 22 cancers, but effects varied substantially by site. Each 5 kg/m(2) increase in BMI was roughly linearly associated with cancers of the uterus (hazard ratio [HR] 1·62, 99% CI 1·56-1·69; p<0·0001), gallbladder (1·31, 1·12-1·52; p<0·0001), kidney (1·25, 1·17-1·33; p<0·0001), cervix (1·10, 1·03-1·17; p=0·00035), thyroid (1·09, 1·00-1·19; p=0·0088), and leukaemia (1·09, 1·05-1·13; p≤0·0001). BMI was positively associated with liver (1·19, 1·12-1·27), colon (1·10, 1·07-1·13), ovarian (1·09, 1.04-1.14), and postmenopausal breast cancers (1·05, 1·03-1·07) overall (all p<0·0001), but these effects varied by underlying BMI or individual-level characteristics. We estimated inverse associations with prostate and premenopausal breast cancer risk, both overall (prostate 0·98, 0·95-1·00; premenopausal breast cancer 0·89, 0·86-0·92) and in never-smokers (prostate 0·96, 0·93-0·99; premenopausal breast cancer 0·89, 0·85-0·94). By contrast, for lung and oral cavity cancer, we observed no association in never smokers (lung 0·99, 0·93-1·05; oral cavity 1·07, 0·91-1·26): inverse associations overall were driven by current smokers and ex-smokers, probably because of residual confounding by smoking amount. Assuming causality, 41% of uterine and 10% or more of gallbladder, kidney, liver, and colon cancers could be attributable to excess weight. We estimated that a 1 kg/m(2) population-wide increase in BMI would result in 3790 additional annual UK patients developing one of the ten cancers positively associated with BMI. INTERPRETATION BMI is associated with cancer risk, with substantial population-level effects. The heterogeneity in the effects suggests that different mechanisms are associated with different cancer sites and different patient subgroups. FUNDING National Institute for Health Research, Wellcome Trust, and Medical Research Council.\",\n \"title\": \"Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5·24 million UK adults\"\n },\n {\n \"docid\": \"20839751\",\n \"text\": \"Apoptosis is a frequent phenomenon in breast cancer and it can be detected by light microscopy in conventional histopathological sections or by special staining techniques. The number of apoptotic cells as a percentage of cells present, or the number of apoptotic cells per square millimetre of neoplastic tissue, is usually described as the apoptotic index (AI). In breast cancer, the AI is not related to tumour size, axillary lymph node metastasis or distant metastasis at diagnosis. It is greater in invasive ductal carcinomas than in other histological types. High AI is also related to high histological grade, high nuclear grade, comedo-type necrosis, lack of tubule formation, and dense infiltration of the tumour by lymphocytes. Sex steroid receptor-negative tumours have greater AIs than the sex steroid receptor-positive ones. Aneuploid breast cancers with high S-phase fractions (SPFs) also have high AI values compared with diploid tumours with low SPFs. p53-Positive breast cancers have high AIs, whereas tumours that are Bcl-2 positive have low AIs. The AI shows a strong positive correlation to all direct or indirect indicators of cell proliferation, such as mitotic index and Ki67 immunolabelling. Univariate survival analyses show that a high AI is linked with unfavourable disease outcome in axillary lymph node-negative and -positive breast cancer, but multivariate analyses indicate that AI is not an independent prognostic factor. In conclusion, a high AI is related to malignant cellular features and indicators of invasiveness and cell proliferation in breast cancer.\",\n \"title\": \"Apoptosis in breast cancer: relationship with other pathological parameters.\"\n },\n {\n \"docid\": \"2425364\",\n \"text\": \"OBJECTIVE To assess the effect of 25-hydroxyvitamin D (25-OHD) levels on pregnancy outcomes and birth variables. DESIGN Systematic review and meta-analysis. DATA SOURCES Medline (1966 to August 2012), PubMed (2008 to August 2012), Embase (1980 to August 2012), CINAHL (1981 to August 2012), the Cochrane database of systematic reviews, and the Cochrane database of registered clinical trials. STUDY SELECTION Studies reporting on the association between serum 25-OHD levels during pregnancy and the outcomes of interest (pre-eclampsia, gestational diabetes, bacterial vaginosis, caesarean section, small for gestational age infants, birth weight, birth length, and head circumference). DATA EXTRACTION Two authors independently extracted data from original research articles, including key indicators of study quality. We pooled the most adjusted odds ratios and weighted mean differences. Associations were tested in subgroups representing different patient characteristics and study quality. RESULTS 3357 studies were identified and reviewed for eligibility. 31 eligible studies were included in the final analysis. Insufficient serum levels of 25-OHD were associated with gestational diabetes (pooled odds ratio 1.49, 95% confidence interval 1.18 to 1.89), pre-eclampsia (1.79, 1.25 to 2.58), and small for gestational age infants (1.85, 1.52 to 2.26). Pregnant women with low serum 25-OHD levels had an increased risk of bacterial vaginosis and low birthweight infants but not delivery by caesarean section. CONCLUSION Vitamin D insufficiency is associated with an increased risk of gestational diabetes, pre-eclampsia, and small for gestational age infants. Pregnant women with low 25-OHD levels had an increased risk of bacterial vaginosis and lower birth weight infants, but not delivery by caesarean section.\",\n \"title\": \"Association between maternal serum 25-hydroxyvitamin D level and pregnancy and neonatal outcomes: systematic review and meta-analysis of observational studies.\"\n },\n {\n \"docid\": \"3524352\",\n \"text\": \"High breast cancer mortality rates have been reported in the northeastern part of the United States, with recent attention focused on Long Island, New York. In this study, the authors investigate whether the high breast cancer mortality is evenly spread over the Northeast, in the sense that any observed clusters of deaths can be explained by chance alone, or whether there are clusters of statistical significance. Demographic data and age-specific breast cancer mortality rates for women were obtained for all 244 counties in 11 northeastern states and for the District of Columbia for 1988-1992. A recently developed spatial scan statistic is used, which searches for clusters of cases without specifying their size or location ahead of time, and which tests for their statistical significance while adjusting for the multiple testing inherent in such a procedure. The basic analysis is adjusted for age, with further analyses examining how the results are affected by incorporating race, urbanicity, and parity as confounding variables. There is a statistically significant and geographically broad cluster of breast cancer deaths in the New York City-Philadelphia, Pennsylvania, metropolitan area (p = 0.0001), which has a 7.4% higher mortality rate than the rest of the Northeast. The cluster remains significant when race, urbanicity, and/or parity are included as confounding variables. Four smaller subclusters within this area are also significant on their own strength: Philadelphia with suburbs (p = 0.0001), Long Island (p = 0.0001), central New Jersey (p = 0.0001), and northeastern New Jersey (p = 0.0001). The elevated breast cancer mortality on Long Island might be viewed less as a unique local phenomenon and more as part of a more general situation involving large parts of the New York City-Philadelphia metropolitan area. The several known and hypothesized risk factors for which we could not adjust and that may explain the detected cluster are most notably age at first birth, age at menarche, age at menopause, breastfeeding, genetic mutations, and environmental factors.\",\n \"title\": \"Breast cancer clusters in the northeast United States: a geographic analysis.\"\n },\n {\n \"docid\": \"8529693\",\n \"text\": \"In this paper we review the associations between maternal and child undernutrition with human capital and risk of adult diseases in low-income and middle-income countries. We analysed data from five long-standing prospective cohort studies from Brazil, Guatemala, India, the Philippines, and South Africa and noted that indices of maternal and child undernutrition (maternal height, birthweight, intrauterine growth restriction, and weight, height, and body-mass index at 2 years according to the new WHO growth standards) were related to adult outcomes (height, schooling, income or assets, offspring birthweight, body-mass index, glucose concentrations, blood pressure). We undertook systematic reviews of studies from low-income and middle-income countries for these outcomes and for indicators related to blood lipids, cardiovascular disease, lung and immune function, cancers, osteoporosis, and mental illness. Undernutrition was strongly associated, both in the review of published work and in new analyses, with shorter adult height, less schooling, reduced economic productivity, and--for women--lower offspring birthweight. Associations with adult disease indicators were not so clear-cut. Increased size at birth and in childhood were positively associated with adult body-mass index and to a lesser extent with blood pressure values, but not with blood glucose concentrations. In our new analyses and in published work, lower birthweight and undernutrition in childhood were risk factors for high glucose concentrations, blood pressure, and harmful lipid profiles once adult body-mass index and height were adjusted for, suggesting that rapid postnatal weight gain--especially after infancy--is linked to these conditions. The review of published works indicates that there is insufficient information about long-term changes in immune function, blood lipids, or osteoporosis indicators. Birthweight is positively associated with lung function and with the incidence of some cancers, and undernutrition could be associated with mental illness. We noted that height-for-age at 2 years was the best predictor of human capital and that undernutrition is associated with lower human capital. We conclude that damage suffered in early life leads to permanent impairment, and might also affect future generations. Its prevention will probably bring about important health, educational, and economic benefits. Chronic diseases are especially common in undernourished children who experience rapid weight gain after infancy.\",\n \"title\": \"Maternal and child undernutrition: consequences for adult health and human capital\"\n },\n {\n \"docid\": \"24249915\",\n \"text\": \"To gain insights into the possible role of oestrogen receptor (ER) beta in breast carcinogenesis, immunohistochemical analysis of ER beta was performed on 512 breast specimens encompassing normal (n = 138), pure ductal carcinoma in situ (n = 16), invasive cancers (n = 319), lymph node metastases (n = 31), and recurrences (n = 8). Real-time polymerase chain reaction (PCR) was used to investigate the methylation status of the ER beta gene in the ER beta negative breast cancer cell lines SkBr3 and MDA-MB-435. A gradual reduction in, but not a complete loss of, ER beta expression was observed during the transition from normal and pre-invasive lesions to invasive cancers, where ER beta was lost in 21% of cases. This was more pronounced in invasive ductal than in lobular carcinomas, a significantly higher proportion of which were ER beta-positive (74% compared with 91%, respectively, p = 0.0004). Examination of paired primary cancers with their axillary lymph node metastases showed that if ER beta was present in the primary tumour, it persisted in the metastasis. Treatment of ER beta-negative cell lines with DNA methyl transferase inhibitors restored ER beta expression, providing experimental evidence that silencing of ER beta in breast carcinomas could be due to promoter hypermethylation. These results suggest that loss of ER beta expression is one of the hallmarks of breast carcinogenesis and that it may be a reversible process involving methylation.\",\n \"title\": \"Reduced expression of oestrogen receptor beta in invasive breast cancer and its re-expression using DNA methyl transferase inhibitors in a cell line model.\"\n },\n {\n \"docid\": \"11360768\",\n \"text\": \"OBJECTIVE To evaluate the effects of dietary and lifestyle interventions in pregnancy on maternal and fetal weight and to quantify the effects of these interventions on obstetric outcomes. DESIGN Systematic review and meta-analysis. DATA SOURCES Major databases from inception to January 2012 without language restrictions. STUDY SELECTION Randomised controlled trials that evaluated any dietary or lifestyle interventions with potential to influence maternal weight during pregnancy and outcomes of pregnancy. DATA SYNTHESIS Results summarised as relative risks for dichotomous data and mean differences for continuous data. RESULTS We identified 44 relevant randomised controlled trials (7278 women) evaluating three categories of interventions: diet, physical activity, and a mixed approach. Overall, there was 1.42 kg reduction (95% confidence interval 0.95 to 1.89 kg) in gestational weight gain with any intervention compared with control. With all interventions combined, there were no significant differences in birth weight (mean difference -50 g, -100 to 0 g) and the incidence of large for gestational age (relative risk 0.85, 0.66 to 1.09) or small for gestational age (1.00, 0.78 to 1.28) babies between the groups, though by itself physical activity was associated with reduced birth weight (mean difference -60 g, -120 to -10 g). Interventions were associated with a reduced the risk of pre-eclampsia (0.74, 0.60 to 0.92) and shoulder dystocia (0.39, 0.22 to 0.70), with no significant effect on other critically important outcomes. Dietary intervention resulted in the largest reduction in maternal gestational weight gain (3.84 kg, 2.45 to 5.22 kg), with improved pregnancy outcomes compared with other interventions. The overall evidence rating was low to very low for important outcomes such as pre-eclampsia, gestational diabetes, gestational hypertension, and preterm delivery. CONCLUSIONS Dietary and lifestyle interventions in pregnancy can reduce maternal gestational weight gain and improve outcomes for both mother and baby. Among the interventions, those based on diet are the most effective and are associated with reductions in maternal gestational weight gain and improved obstetric outcomes.\",\n \"title\": \"Effects of interventions in pregnancy on maternal weight and obstetric outcomes: meta-analysis of randomised evidence\"\n },\n {\n \"docid\": \"26611834\",\n \"text\": \"CONTEXT Maternal depressive symptoms during pregnancy have been reported in some, but not all, studies to be associated with an increased risk of preterm birth (PTB), low birth weight (LBW), and intrauterine growth restriction (IUGR). OBJECTIVE To estimate the risk of PTB, LBW, and IUGR associated with antenatal depression. DATA SOURCES AND STUDY SELECTION We searched for English-language and non-English-language articles via the MEDLINE, PsycINFO, CINAHL, Social Work Abstracts, Social Services Abstracts, and Dissertation Abstracts International databases (January 1980 through December 2009). We aimed to include prospective studies reporting data on antenatal depression and at least 1 adverse birth outcome: PTB (<37 weeks' gestation), LBW (<2500 g), or IUGR (<10th percentile for gestational age). Of 862 reviewed studies, 29 US-published and non-US-published studies met the selection criteria. DATA EXTRACTION Information was extracted on study characteristics, antenatal depression measurement, and other biopsychosocial risk factors and was reviewed twice to minimize error. DATA SYNTHESIS Pooled relative risks (RRs) for the effect of antenatal depression on each birth outcome were calculated using random-effects methods. In studies of PTB, LBW, and IUGR that used a categorical depression measure, pooled effect sizes were significantly larger (pooled RR [95% confidence interval] = 1.39 [1.19-1.61], 1.49 [1.25-1.77], and 1.45 [1.05-2.02], respectively) compared with studies that used a continuous depression measure (1.03 [1.00-1.06], 1.04 [0.99-1.09], and 1.02 [1.00-1.04], respectively). The estimates of risk for categorically defined antenatal depression and PTB and LBW remained significant when the trim-and-fill procedure was used to correct for publication bias. The risk of LBW associated with antenatal depression was significantly larger in developing countries (RR = 2.05; 95% confidence interval, 1.43-2.93) compared with the United States (RR = 1.10; 95% confidence interval, 1.01-1.21) or European social democracies (RR = 1.16; 95% confidence interval, 0.92-1.47). Categorically defined antenatal depression tended to be associated with an increased risk of PTB among women of lower socioeconomic status in the United States. CONCLUSIONS Women with depression during pregnancy are at increased risk for PTB and LBW, although the magnitude of the effect varies as a function of depression measurement, country location, and US socioeconomic status. An important implication of these findings is that antenatal depression should be identified through universal screening and treated.\",\n \"title\": \"A meta-analysis of depression during pregnancy and the risk of preterm birth, low birth weight, and intrauterine growth restriction.\"\n },\n {\n \"docid\": \"12438901\",\n \"text\": \"BACKGROUND For women with oestrogen receptor (ER)-positive early breast cancer, treatment with tamoxifen for 5 years substantially reduces the breast cancer mortality rate throughout the first 15 years after diagnosis. We aimed to assess the further effects of continuing tamoxifen to 10 years instead of stopping at 5 years. METHODS In the worldwide Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) trial, 12,894 women with early breast cancer who had completed 5 years of treatment with tamoxifen were randomly allocated to continue tamoxifen to 10 years or stop at 5 years (open control). Allocation (1:1) was by central computer, using minimisation. After entry (between 1996 and 2005), yearly follow-up forms recorded any recurrence, second cancer, hospital admission, or death. We report effects on breast cancer outcomes among the 6846 women with ER-positive disease, and side-effects among all women (with positive, negative, or unknown ER status). Long-term follow-up still continues. This study is registered, number ISRCTN19652633. FINDINGS Among women with ER-positive disease, allocation to continue tamoxifen reduced the risk of breast cancer recurrence (617 recurrences in 3428 women allocated to continue vs 711 in 3418 controls, p=0·002), reduced breast cancer mortality (331 deaths vs 397 deaths, p=0·01), and reduced overall mortality (639 deaths vs 722 deaths, p=0·01). The reductions in adverse breast cancer outcomes appeared to be less extreme before than after year 10 (recurrence rate ratio [RR] 0·90 [95% CI 0·79–1·02] during years 5–9 and 0·75 [0·62–0·90] in later years; breast cancer mortality RR 0·97 [0·79–1·18] during years 5–9 and 0·71 [0·58–0·88] in later years). The cumulative risk of recurrence during years 5–14 was 21·4% for women allocated to continue versus 25·1% for controls; breast cancer mortality during years 5–14 was 12·2% for women allocated to continue versus 15·0% for controls (absolute mortality reduction 2·8%). Treatment allocation seemed to have no effect on breast cancer outcome among 1248 women with ER-negative disease, and an intermediate effect among 4800 women with unknown ER status. Among all 12,894 women, mortality without recurrence from causes other than breast cancer was little affected (691 deaths without recurrence in 6454 women allocated to continue versus 679 deaths in 6440 controls; RR 0·99 [0·89–1·10]; p=0·84). For the incidence (hospitalisation or death) rates of specific diseases, RRs were as follows: pulmonary embolus 1·87 (95% CI 1·13–3·07, p=0·01 [including 0·2% mortality in both treatment groups]), stroke 1·06 (0·83–1·36), ischaemic heart disease 0·76 (0·60–0·95, p=0·02), and endometrial cancer 1·74 (1·30–2·34, p=0·0002). The cumulative risk of endometrial cancer during years 5–14 was 3·1% (mortality 0·4%) for women allocated to continue versus 1·6% (mortality 0·2%) for controls (absolute mortality increase 0·2%). INTERPRETATION For women with ER-positive disease, continuing tamoxifen to 10 years rather than stopping at 5 years produces a further reduction in recurrence and mortality, particularly after year 10. These results, taken together with results from previous trials of 5 years of tamoxifen treatment versus none, suggest that 10 years of tamoxifen treatment can approximately halve breast cancer mortality during the second decade after diagnosis. FUNDING Cancer Research UK, UK Medical Research Council, AstraZeneca UK, US Army, EU-Biomed.\",\n \"title\": \"Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial\"\n },\n {\n \"docid\": \"16086778\",\n \"text\": \"The biological antagonism between Notch and Numb controls the proliferative/differentiative balance in development and homeostasis. Although altered Notch signaling has been linked to human diseases, including cancer, evidence for a substantial involvement of Notch in human tumors has remained elusive. Here, we show that Numb-mediated control on Notch signaling is lost in ∼50% of human mammary carcinomas, due to specific Numb ubiquitination and proteasomal degradation. Mechanistically, Numb operates as an oncosuppressor, as its ectopic expression in Numb-negative, but not in Numb-positive, tumor cells inhibits proliferation. Increased Notch signaling is observed in Numb-negative tumors, but reverts to basal levels after enforced expression of Numb. Conversely, Numb silencing increases Notch signaling in normal breast cells and in Numb-positive breast tumors. Finally, growth suppression of Numb-negative, but not Numb-positive, breast tumors can be achieved by pharmacological inhibition of Notch. Thus, the Numb/Notch biological antagonism is relevant to the homeostasis of the normal mammary parenchyma and its subversion contributes to human mammary carcinogenesis.\",\n \"title\": \"Loss of negative regulation by Numb over Notch is relevant to human breast carcinogenesis\"\n },\n {\n \"docid\": \"36432234\",\n \"text\": \"Wedelolactone, a plant coumestan, was shown to act as anti-cancer agent for breast and prostate carcinomas in vitro and in vivo targeting multiple cellular proteins including androgen receptors, 5-lipoxygenase and topoisomerase IIα. It is cytotoxic to breast, prostate, pituitary and myeloma cancer cell lines in vitro at μM concentrations. In this study, however, a novel biological activity of nM dose of wedelolactone was demonstrated. Wedelolactone acts as agonist of estrogen receptors (ER) α and β as demonstrated by transactivation of estrogen response element (ERE) in cells transiently expressing either ERα or ERβ and by molecular docking of this coumestan into ligand binding pocket of both ERα and ERβ. In breast cancer cells, wedelolactone stimulates growth of estrogen receptor-positive cells, expression of estrogen-responsive genes and activates rapid non-genomic estrogen signalling. All these effects can be inhibited by pretreatment with pure ER antagonist ICI 182,780 and they are not observed in ER-negative breast cancer cells. We conclude that wedelolactone acts as phytoestrogen in breast cancer cells by stimulating ER genomic and non-genomic signalling pathways.\",\n \"title\": \"Wedelolactone induces growth of breast cancer cells by stimulation of estrogen receptor signalling.\"\n },\n {\n \"docid\": \"30786800\",\n \"text\": \"BACKGROUND The International Lipid-Based Nutrient Supplements Project developed a small-quantity (20 g/d) lipid-based nutrient supplement (LNS) for pregnant and lactating women. OBJECTIVE We evaluated the effects of prenatal LNS supplementation on fetal growth. DESIGN In a community-based, partially double-blind, individually randomized controlled trial, 1320 women ≤20 wk pregnant received 60 mg Fe/400 μg folic acid (IFA), or 1-2 Recommended Dietary Allowances of 18 micronutrients, including 20 mg Fe (MMN), or LNS with the same micronutrients as the MMN group, plus 4 minerals and macronutrients contributing 118 kcal (LNS) daily until delivery. Fetal growth was compared across groups by using intention-to-treat analysis. The primary outcome was birth length. RESULTS This analysis included 1057 women (IFA = 349, MMN = 354, LNS = 354). Groups did not differ significantly in mean birth length, length-for-age z score (LAZ), head circumference, or percentage low birth length but differed in mean birth weight (P = 0.044), weight-for-age z score (WAZ; P = 0.046), and BMI-for-age z score (BMIZ; P = 0.040), with a trend toward differences in low birth weight (P = 0.069). In pairwise comparisons, the LNS group had greater mean birth weight (+85 g; P = 0.040), WAZ (+0.19; P = 0.045), and BMIZ (+0.21; P = 0.035) and a lower risk of low birth weight (RR: 0.61, 95% CI: 0.39, 0.96; P = 0.032) than did the IFA group. The other group differences were not significant. The effect of intervention was modified by mother's parity, age, height, baseline hemoglobin, household food insecurity, and child sex, with parity being the most consistent modifier. Among primiparous women (IFA = 131; MMN = 110; LNS = 128), the LNS group had greater mean birth length (+0.91 cm; P = 0.001), LAZ (+0.47; P = 0.001), weight (+237 g; P < 0.001), WAZ (+0.56; P < 0.001), BMIZ (+0.52; P < 0.001), head circumference (0.50 cm; P = 0.017), and head circumference-for-age z score (+0.40; P = 0.022) than did the IFA group; similar differences were found when comparing the LNS and MMN groups among primiparous women, and no group differences were found among multiparous women. CONCLUSION Prenatal LNS supplementation can improve fetal growth among vulnerable women in Ghana, particularly primiparous women. This trial was registered at clinicaltrials.gov as NCT00970866.\",\n \"title\": \"Lipid-based nutrient supplement increases the birth size of infants of primiparous women in Ghana.\"\n }\n]"}}},{"rowIdx":191,"cells":{"query_id":{"kind":"string","value":"698"},"query":{"kind":"string","value":"Lmna knock-in models are appropriate for testing therapeutic approaches against Hutchinson-Gilford progeria syndrome (HGPS)."},"positive_passages":{"kind":"list like","value":[{"docid":"22544171","text":"Hutchinson-Gilford progeria syndrome (HGPS) is a childhood premature aging disease caused by a spontaneous point mutation in lamin A (encoded by LMNA), one of the major architectural elements of the mammalian cell nucleus. The HGPS mutation activates an aberrant cryptic splice site in LMNA pre-mRNA, leading to synthesis of a truncated lamin A protein and concomitant reduction in wild-type lamin A. Fibroblasts from individuals with HGPS have severe morphological abnormalities in nuclear envelope structure. Here we show that the cellular disease phenotype is reversible in cells from individuals with HGPS. Introduction of wild-type lamin A protein does not rescue the cellular disease symptoms. The mutant LMNA mRNA and lamin A protein can be efficiently eliminated by correction of the aberrant splicing event using a modified oligonucleotide targeted to the activated cryptic splice site. Upon splicing correction, HGPS fibroblasts assume normal nuclear morphology, the aberrant nuclear distribution and cellular levels of lamina-associated proteins are rescued, defects in heterochromatin-specific histone modifications are corrected and proper expression of several misregulated genes is reestablished. Our results establish proof of principle for the correction of the premature aging phenotype in individuals with HGPS.","title":"Reversal of the cellular phenotype in the premature aging disease Hutchinson-Gilford progeria syndrome"}],"string":"[\n {\n \"docid\": \"22544171\",\n \"text\": \"Hutchinson-Gilford progeria syndrome (HGPS) is a childhood premature aging disease caused by a spontaneous point mutation in lamin A (encoded by LMNA), one of the major architectural elements of the mammalian cell nucleus. The HGPS mutation activates an aberrant cryptic splice site in LMNA pre-mRNA, leading to synthesis of a truncated lamin A protein and concomitant reduction in wild-type lamin A. Fibroblasts from individuals with HGPS have severe morphological abnormalities in nuclear envelope structure. Here we show that the cellular disease phenotype is reversible in cells from individuals with HGPS. Introduction of wild-type lamin A protein does not rescue the cellular disease symptoms. The mutant LMNA mRNA and lamin A protein can be efficiently eliminated by correction of the aberrant splicing event using a modified oligonucleotide targeted to the activated cryptic splice site. Upon splicing correction, HGPS fibroblasts assume normal nuclear morphology, the aberrant nuclear distribution and cellular levels of lamina-associated proteins are rescued, defects in heterochromatin-specific histone modifications are corrected and proper expression of several misregulated genes is reestablished. Our results establish proof of principle for the correction of the premature aging phenotype in individuals with HGPS.\",\n \"title\": \"Reversal of the cellular phenotype in the premature aging disease Hutchinson-Gilford progeria syndrome\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"15692098","text":"Hutchinson-Gilford progeria syndrome (HGPS) is a rare but well known entity characterized by extreme short stature, low body weight, early loss of hair, lipodystrophy, scleroderma, decreased joint mobility, osteolysis, and facial features that resemble aged persons. Cardiovascular compromise leads to early demise. Cognitive development is normal. Data on 10 of our own cases and 132 cases from literature are presented. The incidence in the last century in the Netherlands was 1:4,000,000. Sex ratio was 1.2:1. Main first symptoms were failure to thrive (55%), hair loss (40%), skin problems (28%), and lipodystrophy (20%). Mean age at diagnosis was 2.9 years. Growth in weight was more disturbed than growth in height, and growth delay started already prenatally. Mean height > 13 years was 109.0 cm, mean weight was 14.5 kg. Osteolysis was wide-spread but not expressed, except in the viscerocranium, and remained limited to membranous formed bone. Lipodystrophy is generalized, only intra-abdominal fat depositions remain present. Cardiovascular problems are extremely variable, both in age of onset and nature. Stroke and coronary dysfunctioning are most frequent. Pathologic findings in coronaries and aorta resemble sometimes the findings in elderly persons, but can also be much more limited. Loss of smooth muscle cells seems the most important finding. Mean age of demise was 12.6 years. Patients can be subdivided in patients with classical HGPS, which follows an autosomal dominant pattern of inheritance, (almost) all cases representing spontaneous mutations, and in non-classical progeria, in whom growth can be less retarded, scalp hair remains present for a longer time, lipodystrophy is more slowly progressive, osteolysis is more expressed except in the face, and survival well into adulthood is not uncommon. Pattern of inheritance of non-classical progeria is most probably autosomal recessive. The cause of HGPS is an abnormally formed Lamin A, either directly by a mutated LMNA gene, or through abnormal posttranslational processing (ZMPSTE24 gene mutations). Of 34 LMNA mutations found in progeria patients, there were 26 classical p. G608G mutations (76%). Pathogenesis is most likely to follow several different pathways. Potential therapeutic strategies are developed along these lines and include RNA interference techniques and inhibition of the dominant-negative influence of abnormally formed Lamin A on polymerization with normally formed Lamin A.","title":"Hutchinson-Gilford progeria syndrome: review of the phenotype"},{"docid":"834336","text":"Hutchinson–Gilford progeria syndrome (HGPS; OMIM 176670) is an extremely rare but devastating disorder that mimics premature aging.1–3 Affected children appear normal at birth but typically develop failure to thrive in the first two years. Other features include alopecia, micrognathia, loss of subcutaneous fat with prominent veins, abnormal dentition, sclerodermatous skin changes, and osteolysis of the clavicles and distal phalanges. The mean age of death is at age 13 years, most commonly due to atherosclerosis. HGPS is mainly sporadic in occurrence, but a genetic cause has now been implicated following the identification of de novo heterozygous mutations in the LMNA gene in the majority of HGPS patients.4,5 A single family showing autosomal recessive inheritance of homozygous LMNA mutations has also been reported.6 LMNA encodes lamins A and C, components of the nuclear lamina, a meshwork underlying the nuclear envelope that serves as a structural support and is also thought to contribute to chromatin organisation and the regulation of gene expression.7,8 Interestingly, mutations in LMNA have recently been associated with at least eight inherited disorders, known as laminopathies, with differential dystrophic effects on a variety of tissues including muscle, neurones, skin, bone, and adipose tissue (reviewed in Mounkes et al 9). However, the realisation that these disorders share common genetic defects has led to clinical re-evaluation, with emerging evidence of significant phenotypic overlap.10 Hence the laminopathies might reasonably be considered as a spectrum of related diseases. HGPS has phenotypic similarities to several other laminopathies, in particular the atypical Werner’s syndrome11 and mandibuloacral dysplasia (MAD; OMIM 248370 and 608612).12 These diseases are associated with lipodystrophy,3,13 which is the most prominent feature of another laminopathy, familial partial lipodystrophy of the Dunnigan variety (OMIM 151660).14 MAD has been further classified as two …","title":"Compound heterozygous ZMPSTE24 mutations reduce prelamin A processing and result in a severe progeroid phenotype."},{"docid":"34747208","text":"Mutations in the nuclear structural protein lamin A cause the premature aging syndrome Hutchinson-Gilford progeria (HGPS). Whether lamin A plays any role in normal aging is unknown. We show that the same molecular mechanism responsible for HGPS is active in healthy cells. Cell nuclei from old individuals acquire defects similar to those of HGPS patient cells, including changes in histone modifications and increased DNA damage. Age-related nuclear defects are caused by sporadic use, in healthy individuals, of the same cryptic splice site in lamin A whose constitutive activation causes HGPS. Inhibition of this splice site reverses the nuclear defects associated with aging. These observations implicate lamin A in physiological aging.","title":"Lamin A-dependent nuclear defects in human aging."},{"docid":"14178995","text":"The genetic diseases Hutchinson-Gilford progeria syndrome (HGPS) and restrictive dermopathy (RD) arise from accumulation of farnesylated prelamin A because of defects in the lamin A maturation pathway. Both of these diseases exhibit symptoms that can be viewed as accelerated aging. The mechanism by which accumulation of farnesylated prelamin A leads to these accelerated aging phenotypes is not understood. Here we present evidence that in HGPS and RD fibroblasts, DNA damage checkpoints are persistently activated because of the compromise in genomic integrity. Inactivation of checkpoint kinases Ataxia-telangiectasia-mutated (ATM) and ATR (ATM- and Rad3-related) in these patient cells can partially overcome their early replication arrest. Treatment of patient cells with a protein farnesyltransferase inhibitor (FTI) did not result in reduction of DNA double-strand breaks and damage checkpoint signaling, although the treatment significantly reversed the aberrant shape of their nuclei. This suggests that DNA damage accumulation and aberrant nuclear morphology are independent phenotypes arising from prelamin A accumulation in these progeroid syndromes. Since DNA damage accumulation is an important contributor to the symptoms of HGPS, our results call into question the possibility of treatment of HGPS with FTIs alone.","title":"Summary"},{"docid":"7468449","text":"Ever since the first demonstration of their repetitive sequence and unique replication pathway, telomeres have beguiled researchers with how they function in protecting chromosome ends. Of course much has been learned over the years, and we now appreciate that telomeres are comprised of the multimeric protein/DNA shelterin complex and that the formation of t-loops provides protection from DNA damage machinery. Deriving their name from D-loops, t-loops are generated by the insertion of the 3' overhang into telomeric repeats facilitated by the binding of TRF2. Recent studies have uncovered novel forms of chromosome end-structure that may implicate telomere organization in cellular processes beyond its essential role in telomere protection and homeostasis. In particular, we have recently described that t-loops form in a TRF2-dependent manner at interstitial telomere repeat sequences, which we termed interstitial telomere loops (ITLs). These structures are also dependent on association of lamin A/C, a canonical component of the nucleoskeleton that is mutated in myriad human diseases, including human segmental progeroid syndromes. Since ITLs are associated with telomere stability and require functional lamin A/C, our study suggests a mechanistic link between cellular aging (replicative senescence induced by telomere shortening) and organismal aging (modeled by Hutchinson Gilford Progeria Syndrome). Here we speculate on other potential ramifications of ITL formation, from gene expression to genome stability to chromosome structure.","title":"A beginning of the end: new insights into the functional organization of telomeres"},{"docid":"31324978","text":"Progerias are rare genetic diseases characterized by premature aging. Several progeroid disorders are caused by mutations that lead to the accumulation of a lipid-modified (farnesylated) form of prelamin A, a protein that contributes to the structural scaffolding for the cell nucleus. In progeria, the accumulation of farnesyl-prelamin A disrupts this scaffolding, leading to misshapen nuclei. Previous studies have shown that farnesyltransferase inhibitors (FTIs) reverse this cellular abnormality. We tested the efficacy of an FTI (ABT-100) in Zmpste24-deficient mice, a mouse model of progeria. The FTI-treated mice exhibited improved body weight, grip strength, bone integrity, and percent survival at 20 weeks of age. These results suggest that FTIs may have beneficial effects in humans with progeria.","title":"A protein farnesyltransferase inhibitor ameliorates disease in a mouse model of progeria."},{"docid":"7239105","text":"Remarkable advances have been made in recent years towards therapeutics for cognitive impairment in individuals with Down syndrome (DS) by using mouse models. In this review, we briefly describe the phenotypes of mouse models that represent outcome targets for drug testing, the behavioral tests used to assess impairments in cognition and the known mechanisms of action of several drugs that are being used in preclinical studies or are likely to be tested in clinical trials. Overlaps in the distribution of targets and in the pathways that are affected by these diverse drugs in the trisomic brain suggest new avenues for DS research and drug development.","title":"The use of mouse models to understand and improve cognitive deficits in Down syndrome"},{"docid":"38355793","text":"OBJECTIVE A20 is a TNF-inducible primary response gene, which has been found to have antiapoptotic function in several cancer cells. This study investigates A20 expression in human glioma tissues and four glioma cell lines, and its effect on tumorigenesis of glioma cells and a mouse tumor model. METHODS Human glioma tissue samples and cells were subject to reverse transcription-PCR (RT-PCR), western blotting and immunohistochemistry. Glioma cells was tested by flow cytometry. A xenograft tumor model in mice was utilized to examine the knock-down effect of specific A20 siRNAs on tumorigenesis. RESULTS A20 was overexpressed in clinical glioma tissue samples (63.9%) and correlated with clinical staging. All four human glioma cell lines expressed A20, among which U87 displayed the strongest expression signals. Inhibiting A20 expression by siRNAs in vitro reduced the growth rates of glioma cells and resulted in G1/S arrest and increased apoptosis. In a mouse tumor model, local administration of siRNA significantly suppressed solid tumor growth. CONCLUSIONS A20 was overexpressed both in human glioma tissues and cell lines, and inhibiting A20 expression greatly slowed tumor cell growth in culture and in mice. These findings indicated that A20 is involved in tumorigenesis of human glioma, and may serve as a future therapeutic target.","title":"A20 is overexpressed in glioma cells and may serve as a potential therapeutic target."},{"docid":"31844040","text":"Two-component systems (TCSs) are widely employed by bacteria to sense specific external signals and conduct an appropriate response via a phosphorylation cascade within the cell. The TCS of the agr operon in the bacterium Staphylococcus aureus forms part of a regulatory process termed quorum sensing, a cell-to-cell communication mechanism used to assess population density. Since S. aureus manipulates this \"knowledge\" in order to co-ordinate production of its armoury of exotoxin virulence factors required to promote infection, it is important to understand fully how this process works. We present three models of the agr operon, each incorporating a different phosphorylation cascade for the TCS since the precise nature of the cascade is not fully understood. Using numerical and asymptotic techniques we examine the effects of inhibitor therapy, a novel approach to controlling bacterial infection through the attenuation of virulence, on each of these three cascades. We present results which, if evaluated against appropriate experimental data, provide insights into the potential effectiveness of such therapy. Moreover, the TCS models presented here are of broad relevance given that TCSs are widely conserved throughout the bacterial kingdom.","title":"A mathematical investigation of the effects of inhibitor therapy on three putative phosphorylation cascades governing the two-component system of the agr operon."},{"docid":"18414462","text":"Although the lung is a defining feature of air-breathing animals, the pathway controlling the formation of type I pneumocytes, the cells that mediate gas exchange, is poorly understood. In contrast, the glucocorticoid receptor and its cognate ligand have long been known to promote type II pneumocyte maturation; prenatal administration of glucocorticoids is commonly used to attenuate the severity of infant respiratory distress syndrome (RDS). Here we show that knock-in mutations of the nuclear co-repressor SMRT (silencing mediator of retinoid and thyroid hormone receptors) in C57BL/6 mice (SMRTmRID) produces a previously unidentified respiratory distress syndrome caused by prematurity of the type I pneumocyte. Though unresponsive to glucocorticoids, treatment with anti-thyroid hormone drugs (propylthiouracil or methimazole) completely rescues SMRT-induced RDS, suggesting an unrecognized and essential role for the thyroid hormone receptor (TR) in lung development. We show that TR and SMRT control type I pneumocyte differentiation through Klf2, which, in turn, seems to directly activate the type I pneumocyte gene program. Conversely, mice without lung Klf2 lack mature type I pneumocytes and die shortly after birth, closely recapitulating the SMRTmRID phenotype. These results identify TR as a second nuclear receptor involved in lung development, specifically type I pneumocyte differentiation, and suggest a possible new type of therapeutic option in the treatment of RDS that is unresponsive to glucocorticoids.","title":"Thyroid Hormone Receptor Repression Linked to Type I Pneumocyte Associated Respiratory Distress Syndrome"},{"docid":"16232581","text":"We develop a reversible jump Markov chain Monte Carlo approach to estimating the posterior distribution of phylogenies based on aligned DNA/RNA sequences under several hierarchical evolutionary models. Using a proper, yet nontruncated and uninformative prior, we demonstrate the advantages of the Bayesian approach to hypothesis testing and estimation in phylogenetics by comparing different models for the infinitesimal rates of change among nucleotides, for the number of rate classes, and for the relationships among branch lengths. We compare the relative probabilities of these models and the appropriateness of a molecular clock using Bayes factors. Our most general model, first proposed by Tamura and Nei, parameterizes the infinitesimal change probabilities among nucleotides (A, G, C, T/U) into six parameters, consisting of three parameters for the nucleotide stationary distribution, two rate parameters for nucleotide transitions, and another parameter for nucleotide transversions. Nested models include the Hasegawa, Kishino, and Yano model with equal transition rates and the Kimura model with a uniform stationary distribution and equal transition rates. To illustrate our methods, we examine simulated data, 16S rRNA sequences from 15 contemporary eubacteria, halobacteria, eocytes, and eukaryotes, 9 primates, and the entire HIV genome of 11 isolates. We find that the Kimura model is too restrictive, that the Hasegawa, Kishino, and Yano model can be rejected for some data sets, that there is evidence for more than one rate class and a molecular clock among similar taxa, and that a molecular clock can be rejected for more distantly related taxa.","title":"Bayesian selection of continuous-time Markov chain evolutionary models."},{"docid":"2264455","text":"There is no licenced vaccine against any human parasitic disease and Plasmodium falciparum malaria, a major cause of infectious mortality, presents a great challenge to vaccine developers. This has led to the assessment of a wide variety of approaches to malaria vaccine design and development, assisted by the availability of a safe challenge model for small-scale efficacy testing of vaccine candidates. Malaria vaccine development has been at the forefront of assessing many new vaccine technologies including novel adjuvants, vectored prime-boost regimes and the concept of community vaccination to block malaria transmission. Most current vaccine candidates target a single stage of the parasite's life cycle and vaccines against the early pre-erythrocytic stages have shown most success. A protein in adjuvant vaccine, working through antibodies against sporozoites, and viral vector vaccines targeting the intracellular liver-stage parasite with cellular immunity show partial efficacy in humans, and the anti-sporozoite vaccine is currently in phase III trials. However, a more effective malaria vaccine suitable for widespread cost-effective deployment is likely to require a multi-component vaccine targeting more than one life cycle stage. The most attractive near-term approach to develop such a product is to combine existing partially effective pre-erythrocytic vaccine candidates.","title":"Vaccines against malaria"},{"docid":"33884866","text":"OBJECTIVE The sphingosine-1-phosphate (S1P) receptor agonist fingolimod (FTY720), that has shown efficacy in advanced multiple sclerosis clinical trials, decreases reperfusion injury in heart, liver, and kidney. We therefore tested the therapeutic effects of fingolimod in several rodent models of focal cerebral ischemia. To assess the translational significance of these findings, we asked whether fingolimod improved long-term behavioral outcomes, whether delayed treatment was still effective, and whether neuroprotection can be obtained in a second species. METHODS We used rodent models of middle cerebral artery occlusion and cell-culture models of neurotoxicity and inflammation to examine the therapeutic potential and mechanisms of neuroprotection by fingolimod. RESULTS In a transient mouse model, fingolimod reduced infarct size, neurological deficit, edema, and the number of dying cells in the core and periinfarct area. Neuroprotection was accompanied by decreased inflammation, as fingolimod-treated mice had fewer activated neutrophils, microglia/macrophages, and intercellular adhesion molecule-1 (ICAM-1)-positive blood vessels. Fingolimod-treated mice showed a smaller infarct and performed better in behavioral tests up to 15 days after ischemia. Reduced infarct was observed in a permanent model even when mice were treated 4 hours after ischemic onset. Fingolimod also decreased infarct size in a rat model of focal ischemia. Fingolimod did not protect primary neurons against glutamate excitotoxicity or hydrogen peroxide, but decreased ICAM-1 expression in brain endothelial cells stimulated by tumor necrosis factor alpha. INTERPRETATION These findings suggest that anti-inflammatory mechanisms, and possibly vasculoprotection, rather than direct effects on neurons, underlie the beneficial effects of fingolimod after stroke. S1P receptors are a highly promising target in stroke treatment.","title":"Fingolimod provides long-term protection in rodent models of cerebral ischemia."},{"docid":"34873974","text":"OBJECTIVE To obtain summary estimates of the accuracy of a single baseline measurement of the Elecsys Troponin T high-sensitive assay (Roche Diagnostics) for the diagnosis of acute myocardial infarction in patients presenting to the emergency department. DESIGN Systematic review and meta-analysis of diagnostic test accuracy studies. DATA SOURCES Medline, Embase, and other relevant electronic databases were searched for papers published between January 2006 and December 2013. STUDY SELECTION Studies were included if they evaluated the diagnostic accuracy of a single baseline measurement of Elecsys Troponin T high-sensitive assay for the diagnosis of acute myocardial infarction in patients presenting to the emergency department with suspected acute coronary syndrome. STUDY APPRAISAL AND DATA SYNTHESIS The first author screened all titles and abstracts identified through the searches and selected all potentially relevant papers. The screening of the full texts, the data extraction, and the methodological quality assessment, using the adapted QUADAS-2 tool, were conducted independently by two reviewers with disagreements being resolved through discussion or arbitration. If appropriate, meta-analysis was conducted using the hierarchical bivariate model. RESULTS Twenty three studies reported the performance of the evaluated assay at presentation. The results for 14 ng/L and 3-5 ng/L cut-off values were pooled separately. At 14 ng/L (20 papers), the summary sensitivity was 89.5% (95% confidence interval 86.3% to 92.1%) and the summary specificity was 77.1% (68.7% to 83.7%). At 3-5 ng/L (six papers), the summary sensitivity was 97.4% (94.9% to 98.7%) and the summary specificity was 42.4% (31.2% to 54.5%). This means that if 21 of 100 consecutive patients have the target condition (21%, the median prevalence across the studies), 2 (95% confidence interval 2 to 3) of 21 patients with acute myocardial infarction will be missed (false negatives) if 14 ng/L is used as a cut-off value and 18 (13 to 25) of 79 patients without acute myocardial infarction will test positive (false positives). If the 3-5 ng/L cut-off value is used, <1 (0 to 1) patient with acute myocardial infarction will be missed and 46 (36 to 54) patients without acute myocardial infarction will test positive. CONCLUSIONS The results indicate that a single baseline measurement of the Elecsys Troponin T high-sensitive assay could be used to rule out acute myocardial infarction if lower cut-off values such as 3 ng/L or 5 ng/L are used. However, this method should be part of a comprehensive triage strategy and may not be appropriate for patients who present less than three hours after symptom onset. Care must also be exercised because of the higher imprecision of the evaluated assay and the greater effect of lot-to-lot reagent variation at low troponin concentrations. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration number CRD42013003926.","title":"Diagnostic accuracy of single baseline measurement of Elecsys Troponin T high-sensitive assay for diagnosis of acute myocardial infarction in emergency department: systematic review and meta-analysis"},{"docid":"24496245","text":"Genetic evidence implicates the loss of bone morphogenetic protein type II receptor (BMPR-II) signaling in the endothelium as an initiating factor in pulmonary arterial hypertension (PAH). However, selective targeting of this signaling pathway using BMP ligands has not yet been explored as a therapeutic strategy. Here, we identify BMP9 as the preferred ligand for preventing apoptosis and enhancing monolayer integrity in both pulmonary arterial endothelial cells and blood outgrowth endothelial cells from subjects with PAH who bear mutations in the gene encoding BMPR-II, BMPR2. Mice bearing a heterozygous knock-in allele of a human BMPR2 mutation, R899X, which we generated as an animal model of PAH caused by BMPR-II deficiency, spontaneously developed PAH. Administration of BMP9 reversed established PAH in these mice, as well as in two other experimental PAH models, in which PAH develops in response to either monocrotaline or VEGF receptor inhibition combined with chronic hypoxia. These results demonstrate the promise of direct enhancement of endothelial BMP signaling as a new therapeutic strategy for PAH.","title":"Selective enhancement of endothelial BMPR-II with BMP9 reverses pulmonary arterial hypertension"},{"docid":"7317051","text":"Pancreatic ductal adenocarcinoma (PDA) represents an unmet therapeutic challenge. PDA is addicted to the activity of the mutated KRAS oncogene which is considered so far an undruggable therapeutic target. We propose an approach to target KRAS effectively in patients using RNA interference. To meet this challenge, we have developed a local prolonged siRNA delivery system (Local Drug EluteR, LODER) shedding siRNA against the mutated KRAS (siG12D LODER). The siG12D LODER was assessed for its structural, release, and delivery properties in vitro and in vivo. The effect of the siG12D LODER on tumor growth was assessed in s.c. and orthotopic mouse models. KRAS silencing effect was further assessed on the KRAS downstream signaling pathway. The LODER-encapsulated siRNA was stable and active in vivo for 155 d. Treatment of PDA cells with siG12D LODER resulted in a significant decrease in KRAS levels, leading to inhibition of proliferation and epithelial-mesenchymal transition. In vivo, siG12D LODER impeded the growth of human pancreatic tumor cells and prolonged mouse survival. We report a reproducible and safe delivery platform based on a miniature biodegradable polymeric matrix, for the controlled and prolonged delivery of siRNA. This technology provides the following advantages: (i) siRNA is protected from degradation; (ii) the siRNA is slowly released locally within the tumor for prolonged periods; and (iii) the siG12D LODER elicits a therapeutic effect, thereby demonstrating that mutated KRAS is indeed a druggable target.","title":"Mutant KRAS is a druggable target for pancreatic cancer."},{"docid":"14116046","text":"Retinoic acid-related orphan receptors RORα and RORγ play a regulatory role in lipid/glucose homeostasis and various immune functions, and have been implicated in metabolic syndrome and several inflammatory diseases. RORα-deficient mice are protected against age- and diet-induced obesity, hepatosteatosis, and insulin resistance. The resistance to hepatosteatosis in RORα-deficient mice is related to the reduced expression of several genes regulating lipid synthesis, transport, and storage. Adipose tissue-associated inflammation, which plays a critical role in the development of insulin resistance, is considerably diminished in RORα-deficient mice as indicated by the reduced infiltration of M1 macrophages and decreased expression of many proinflammatory genes. Deficiency in RORγ also protects against diet-induced insulin resistance by a mechanism that appears different from that in RORα deficiency. Recent studies indicated that RORs provide an important link between the circadian clock machinery and its regulation of metabolic genes and metabolic syndrome. As ligand-dependent transcription factors, RORs may provide novel therapeutic targets in the management of obesity and associated metabolic diseases, including hepatosteatosis, adipose tissue-associated inflammation, and insulin resistance.","title":"Retinoic acid-related orphan receptors α and γ: key regulators of lipid/glucose metabolism, inflammation, and insulin sensitivity"},{"docid":"2837758","text":"Epitope vaccine is a promising option for therapeutic vaccination against Helicobacter pylori (H. pylori) infection. In this study, we constructed a multi-epitope vaccine with five epitopes and mucosal adjuvant E. coli heat-labile enterotoxin B subunit (LTB) named HUepi-LTB and evaluated its therapeutic effect against H. pylori infection in BALB/c mice model. HUepi-LTB containing three Th epitopes from UreB and two B cell epitopes from UreB and HpaA was constructed and expressed in E. coli. Oral therapeutic immunization with HUepi-LTB significantly decreased H. pylori colonization compared with oral immunization with PBS, and the protection was correlated with antigen-specific CD4+ T cells and IgG and mucosal IgA antibody responses. This multi-epitope vaccine may be a promising vaccine candidate that may help to control H. pylori infection.","title":"Therapeutic efficacy of a multi-epitope vaccine against Helicobacter pylori infection in BALB/c mice model."},{"docid":"8690595","text":"Although genetic association studies have been with us for many years, even for the simplest analyses there is little consensus on the most appropriate statistical procedures. Here I give an overview of statistical approaches to population association studies, including preliminary analyses (Hardy–Weinberg equilibrium testing, inference of phase and missing data, and SNP tagging), and single-SNP and multipoint tests for association. My goal is to outline the key methods with a brief discussion of problems (population structure and multiple testing), avenues for solutions and some ongoing developments.","title":"A tutorial on statistical methods for population association studies"},{"docid":"878526","text":"Despite progress in the development of drugs that efficiently target cancer cells, treatments for metastatic tumours are often ineffective. The now well-established dependency of cancer cells on their microenvironment suggests that targeting the non-cancer-cell component of the tumour might form a basis for the development of novel therapeutic approaches. However, the as-yet poorly characterized contribution of host responses during tumour growth and metastatic progression represents a limitation to exploiting this approach. Here we identify neutrophils as the main component and driver of metastatic establishment within the (pre-)metastatic lung microenvironment in mouse breast cancer models. Neutrophils have a fundamental role in inflammatory responses and their contribution to tumorigenesis is still controversial. Using various strategies to block neutrophil recruitment to the pre-metastatic site, we demonstrate that neutrophils specifically support metastatic initiation. Importantly, we find that neutrophil-derived leukotrienes aid the colonization of distant tissues by selectively expanding the sub-pool of cancer cells that retain high tumorigenic potential. Genetic or pharmacological inhibition of the leukotriene-generating enzyme arachidonate 5-lipoxygenase (Alox5) abrogates neutrophil pro-metastatic activity and consequently reduces metastasis. Our results reveal the efficacy of using targeted therapy against a specific tumour microenvironment component and indicate that neutrophil Alox5 inhibition may limit metastatic progression.","title":"Neutrophils support lung colonization of metastasis-initiating breast cancer cells"},{"docid":"20372201","text":"A growing body of evidence supports the notion that malignant tumors are heterogeneous and contain diverse subpopulations of cells with unique characteristics including the ability to initiate a tumor and metastasize. This phenomenon might be explained by the so-called cancer stem cell (CSC) theory. Recent technological developments have allowed a deeper understanding and characterization of CSCs. Even though the application of this theory to hematopoietic malignancies and solid tumors holds promise for new ways to treat cancer, it also brings some skepticism. Efficacious therapeutic approaches targeting the CSC population should be explored to overcome therapeutic failure and improve patient outcomes. This review will focus on the intrinsic and extrinsic regulation of CSCs, as well as the development of therapeutic approaches against CSCs, predominantly focusing on gastrointestinal malignancies.","title":"Cancer stem cell theory in gastrointestinal malignancies: recent progress and upcoming challenges"},{"docid":"4544916","text":"To efficiently counteract pathogens, plants rely on a complex set of immune responses that are tightly regulated to allow the timely activation, appropriate duration and adequate amplitude of defense programs. The coordination of the plant immune response is known to require the activity of the ubiquitin/proteasome system, which controls the stability of proteins in eukaryotes. Here, we demonstrate that the N-end rule pathway, a subset of the ubiquitin/proteasome system, regulates the defense against a wide range of bacterial and fungal pathogens in the model plant Arabidopsis thaliana. We show that this pathway positively regulates the biosynthesis of plant-defense metabolites such as glucosinolates, as well as the biosynthesis and response to the phytohormone jasmonic acid, which plays a key role in plant immunity. Our results also suggest that the arginylation branch of the N-end rule pathway regulates the timing and amplitude of the defense program against the model pathogen Pseudomonas syringae AvrRpm1.","title":"The N-end rule pathway regulates pathogen responses in plants."},{"docid":"17682477","text":"To test the feasibility of a single T-cell manipulation to eliminate alloreactivity while sparing antiviral and antitumor T cells, we infused 12 haploidentical hematopoietic stem cell transplant patients with increasing numbers of alloreplete haploidentical T cells expressing the inducible caspase 9 suicide gene (iC9-T cells). We determined whether the iC9-T cells produced immune reconstitution and if any resultant graft-versus-host disease (GVHD) could be controlled by administration of a chemical inducer of dimerization (CID; AP1903/Rimiducid). All patients receiving >10(4) alloreplete iC9-T lymphocytes per kilogram achieved rapid reconstitution of immune responses toward 5 major pathogenic viruses and concomitant control of active infections. Four patients received a single AP1903 dose. CID infusion eliminated 85% to 95% of circulating CD3(+)CD19(+) T cells within 30 minutes, with no recurrence of GVHD within 90 days. In one patient, symptoms and signs of GVHD-associated cytokine release syndrome (CRS-hyperpyrexia, high levels of proinflammatory cytokines, and rash) resolved within 2 hours of AP1903 infusion. One patient with varicella zoster virus meningitis and acute GVHD had iC9-T cells present in the cerebrospinal fluid, which were reduced by >90% after CID. Notably, virus-specific T cells recovered even after AP1903 administration and continued to protect against infection. Hence, alloreplete iC9-T cells can reconstitute immunity posttransplant and administration of CID can eliminate them from both peripheral blood and the central nervous system (CNS), leading to rapid resolution of GVHD and CRS. The approach may therefore be useful for the rapid and effective treatment of toxicities associated with infusion of engineered T lymphocytes. This trial was registered at www.clinicaltrials.gov as #NCT01494103.","title":"Inducible caspase-9 suicide gene controls adverse effects from alloreplete T cells after haploidentical stem cell transplantation."},{"docid":"44827480","text":"BACKGROUND Few data exist about the implementation of contemporary oral antiplatelet treatment guidelines in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). METHODS GReek AntiPlatelet rEgistry (GRAPE), initiated on January 2012, is a prospective, observational, multicenter cohort study focusing on contemporary use of P2Y12 inhibitors. In 1434 patients we evaluated appropriateness of P2Y12 selection initially and at discharge by applying an eligibility-assessing algorithm based on P2Y12 inhibitors' contraindications/specific warnings and precautions. RESULTS Appropriate, less preferable and inappropriate P2Y12 inhibitor selections were made initially in 45.8%, 47.2% and 6.6% and at discharge in 64.1%, 29.2% and 6.6% of patients, respectively. The selection of clopidogrel was most commonly less preferable, both initially (69.7%) and at discharge (75.6%). Appropriate selection of newer agents was high initially (79.2%-82.8%), with further increase as selection at discharge (89.4%-89.8%). Inappropriate selection of the newer agents was 17.2%-20.8% initially, decreasing to 10.2%-10.6% at discharge. Conditions and co-medications related to increased bleeding risk, presentation with ST elevation myocardial infarction and the absence of reperfusion within the first 24h were the most powerful predictors of appropriate P2Y12 selection initially, whereas age ≥75 years, conditions and co-medications related to increased bleeding risk and regional trends mostly affected appropriate P2Y12 selection at discharge. CONCLUSIONS In GRAPE, adherence with the recently released guidelines on oral antiplatelet therapy was satisfactory. Clopidogrel was most commonly used as a less preferable selection, while prasugrel or ticagrelor selection was mostly appropriate. Certain factors may predict initial and at discharge guideline implementation. Clinical Trial Registration-clinicaltrials.gov Identifier: NCT01774955 http://clinicaltrials.gov/.","title":"Implementation of contemporary oral antiplatelet treatment guidelines in patients with acute coronary syndrome undergoing percutaneous coronary intervention: a report from the GReek AntiPlatelet rEgistry (GRAPE)."},{"docid":"8133050","text":"Many microparasites infect new hosts with specialized life stages, requiring a subset of the parasite population to forgo proliferation and develop into transmission forms. Transmission stage production influences infectivity, host exploitation, and the impact of medical interventions like drug treatment. Predicting how parasites will respond to public health efforts on both epidemiological and evolutionary timescales requires understanding transmission strategies. These strategies can rarely be observed directly and must typically be inferred from infection dynamics. Using malaria as a case study, we test previously described methods for inferring transmission stage investment against simulated data generated with a model of within-host infection dynamics, where the true transmission investment is known. We show that existing methods are inadequate and potentially very misleading. The key difficulty lies in separating transmission stages produced by different generations of parasites. We develop a new approach that performs much better on simulated data. Applying this approach to real data from mice infected with a single Plasmodium chabaudi strain, we estimate that transmission investment varies from zero to 20%, with evidence for variable investment over time in some hosts, but not others. These patterns suggest that, even in experimental infections where host genetics and other environmental factors are controlled, parasites may exhibit remarkably different patterns of transmission investment.","title":"Quantifying Transmission Investment in Malaria Parasites"},{"docid":"12030735","text":"OBJECTIVE Limited information is available about the metabolic syndrome in Asians. Furthermore, the definition of central obesity using waist circumference may not be appropriate for Asians. The objectives of this study were to determine the optimal waist circumference for diagnosing central obesity in Asians and to estimate the prevalence of the metabolic syndrome in an Asian population. RESEARCH DESIGN AND METHODS We used data from the 1998 Singapore National Health Survey, a cross-sectional survey involving 4,723 men and women of Chinese, Malay, and Asian-Indian ethnicity aged 18-69 years. Receiver operating characteristic analysis suggested that waist circumference >80 cm in women and >90 cm in men was a more appropriate definition of central obesity in this population. The prevalence of the metabolic syndrome was then determined using the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria with and without the modified waist circumference criteria. RESULTS In Asians, decreasing waist circumference increased the crude prevalence of the metabolic syndrome from 12.2 to 17.9%. Using the modified Asian criteria, the prevalence of the metabolic syndrome increased from 2.9% in those aged 18-30 years to 31.0% in those aged 60-69 years. It was more common in men (prevalence 20.9% in men versus 15.5% in women; P < 0.001) and Asian Indians (prevalence 28.8% in Asian-Indians, 24.2% in Malays, and 14.8% in Chinese; P < 0.001). CONCLUSIONS NCEP ATP III criteria, applied to an Asian population, will underestimate the population at risk. With a lower waist circumference cutoff, the prevalence of the metabolic syndrome is comparable to that in Western populations. Ethnic differences are likely to exist between populations across Asia.","title":"Can we apply the National Cholesterol Education Program Adult Treatment Panel definition of the metabolic syndrome to Asians?"},{"docid":"28017005","text":"Assessment for selection in medicine and the health professions should follow the same quality assurance processes as in-course assessment. The literature on selection is limited and is not strongly theoretical or conceptual. For written testing, there is evidence of the predictive validity of Medical College Admission Test (MCAT) for medical school and licensing examination performance. There is also evidence for the predictive validity of grade point average, particularly in combination with MCAT for graduate entry but little evidence about the predictive validity of school leaver scores. Interviews have not been shown to be robust selection measures. Studies of multiple mini-interviews have indicated good predictive validity and reliability. Of other measures used in selection, only the growing interest in personality testing appears to warrant future work. Widening access to medical and health professional programmes is an increasing priority and relates to the social accountability mandate of medical and health professional schools. While traditional selection measures do discriminate against various population groups, there is little evidence on the effect of non-traditional measures in widening access. Preparation and outreach programmes show most promise. In summary, the areas of consensus for assessment for selection are small in number. Recommendations for future action focus on the adoption of principles of good assessment and curriculum alignment, use of multi-method programmatic approaches, development of interdisciplinary frameworks and utilisation of sophisticated measurement models. The social accountability mandate of medical and health professional schools demands that social inclusion, workforce issues and widening of access are embedded in the principles of good assessment for selection.","title":"Assessment for selection for the health care professions and specialty training: consensus statement and recommendations from the Ottawa 2010 Conference."},{"docid":"13965483","text":"Epitope vaccine based on the enzyme urease of Helicobacter pylori is a promising option for prophylactic and therapeutic vaccination against H. pylori infection. In our previous study, the epitope vaccine CTB-UA, which was composed of the mucosal adjuvant cholera toxin B subunit (CTB) and an epitope (UreA183–203) from the H. pylori urease A subunit (UreA) was constructed. This particular vaccine was shown to have good immunogenicity and immunoreactivity and could induce specific neutralizing antibodies, which exhibited effectively inhibitory effects on the enzymatic activity of H. pylori urease. In this study, the prophylactic and therapeutic efficacy of the epitope vaccine CTB-UA was evaluated in a BALB/c mice model. The experimental results indicated that oral prophylactic or therapeutic immunization with CTB-UA significantly decreased H. pylori colonization compared with oral immunization with PBS. The results also revealed that the protection was correlated with antigen-specific IgG, IgA, and mucosal secretory IgA antibody responses. CTB-UA may be a promising vaccine candidate for the control of H. pylori infection.","title":"Prophylactic and therapeutic efficacy of the epitope vaccine CTB-UA against Helicobacter pylori infection in a BALB/c mice model"},{"docid":"1967410","text":"Although significant progress has occurred in the past 20 years regarding our understanding of Alzheimer disease pathogenesis, we have yet to identify disease-modifying therapeutics capable of substantially altering the clinical course of this prevalent neurodegenerative disease. In this short review, we discuss 2 approaches that are currently being tested clinically (γ-secretase inhibition and γ-secretase modulation) and emphasize the significant differences between these 2 therapeutic approaches. We also discuss certain genetic- and biomarker-based translational and clinical trial paradigms that may assist in developing a useful therapeutic agent.","title":"Potential use of γ-secretase modulators in the treatment of Alzheimer disease."},{"docid":"16605494","text":"BACKGROUND Whereas many causes and mechanisms of neurodegenerative diseases have been identified, very few therapeutic strategies have emerged in parallel. One possible explanation is that successful treatment strategy may require simultaneous targeting of more than one molecule of pathway. A new therapeutic approach to have emerged recently is the engagement of microRNAs (miRNAs), which affords the opportunity to target multiple cellular pathways simultaneously using a single sequence. METHODOLOGY/PRINCIPAL FINDINGS We identified miR-22 as a potentially neuroprotective miRNA based on its predicted regulation of several targets implicated in Huntington's disease (histone deacetylase 4 (HDAC4), REST corepresor 1 (Rcor1) and regulator of G-protein signaling 2 (Rgs2)) and its diminished expression in Huntington's and Alzheimer's disease brains. We then tested the hypothesis that increasing cellular levels of miRNA-22 would achieve neuroprotection in in vitro models of neurodegeneration. As predicted, overexpression of miR-22 inhibited neurodegeneration in primary striatal and cortical cultures exposed to a mutated human huntingtin fragment (Htt171-82Q). Overexpression of miR-22 also decreased neurodegeneration in primary neuronal cultures exposed to 3-nitropropionic acid (3-NP), a mitochondrial complex II/III inhibitor. In addition, miR-22 improved neuronal viability in an in vitro model of brain aging. The mechanisms underlying the effects of miR-22 included a reduction in caspase activation, consistent with miR-22's targeting the pro-apoptotic activities of mitogen-activated protein kinase 14/p38 (MAPK14/p38) and tumor protein p53-inducible nuclear protein 1 (Tp53inp1). Moreover, HD-specific effects comprised not only targeting HDAC4, Rcor1 and Rgs2 mRNAs, but also decreasing focal accumulation of mutant Htt-positive foci, which occurred via an unknown mechanism. CONCLUSIONS These data show that miR-22 has multipartite anti-neurodegenerative activities including the inhibition of apoptosis and the targeting of mRNAs implicated in the etiology of HD. These results motivate additional studies to evaluate the feasibility and therapeutic efficacy of manipulating miR-22 in vivo.","title":"MicroRNA-22 (miR-22) Overexpression Is Neuroprotective via General Anti-Apoptotic Effects and May also Target Specific Huntington’s Disease-Related Mechanisms"}],"string":"[\n {\n \"docid\": \"15692098\",\n \"text\": \"Hutchinson-Gilford progeria syndrome (HGPS) is a rare but well known entity characterized by extreme short stature, low body weight, early loss of hair, lipodystrophy, scleroderma, decreased joint mobility, osteolysis, and facial features that resemble aged persons. Cardiovascular compromise leads to early demise. Cognitive development is normal. Data on 10 of our own cases and 132 cases from literature are presented. The incidence in the last century in the Netherlands was 1:4,000,000. Sex ratio was 1.2:1. Main first symptoms were failure to thrive (55%), hair loss (40%), skin problems (28%), and lipodystrophy (20%). Mean age at diagnosis was 2.9 years. Growth in weight was more disturbed than growth in height, and growth delay started already prenatally. Mean height > 13 years was 109.0 cm, mean weight was 14.5 kg. Osteolysis was wide-spread but not expressed, except in the viscerocranium, and remained limited to membranous formed bone. Lipodystrophy is generalized, only intra-abdominal fat depositions remain present. Cardiovascular problems are extremely variable, both in age of onset and nature. Stroke and coronary dysfunctioning are most frequent. Pathologic findings in coronaries and aorta resemble sometimes the findings in elderly persons, but can also be much more limited. Loss of smooth muscle cells seems the most important finding. Mean age of demise was 12.6 years. Patients can be subdivided in patients with classical HGPS, which follows an autosomal dominant pattern of inheritance, (almost) all cases representing spontaneous mutations, and in non-classical progeria, in whom growth can be less retarded, scalp hair remains present for a longer time, lipodystrophy is more slowly progressive, osteolysis is more expressed except in the face, and survival well into adulthood is not uncommon. Pattern of inheritance of non-classical progeria is most probably autosomal recessive. The cause of HGPS is an abnormally formed Lamin A, either directly by a mutated LMNA gene, or through abnormal posttranslational processing (ZMPSTE24 gene mutations). Of 34 LMNA mutations found in progeria patients, there were 26 classical p. G608G mutations (76%). Pathogenesis is most likely to follow several different pathways. Potential therapeutic strategies are developed along these lines and include RNA interference techniques and inhibition of the dominant-negative influence of abnormally formed Lamin A on polymerization with normally formed Lamin A.\",\n \"title\": \"Hutchinson-Gilford progeria syndrome: review of the phenotype\"\n },\n {\n \"docid\": \"834336\",\n \"text\": \"Hutchinson–Gilford progeria syndrome (HGPS; OMIM 176670) is an extremely rare but devastating disorder that mimics premature aging.1–3 Affected children appear normal at birth but typically develop failure to thrive in the first two years. Other features include alopecia, micrognathia, loss of subcutaneous fat with prominent veins, abnormal dentition, sclerodermatous skin changes, and osteolysis of the clavicles and distal phalanges. The mean age of death is at age 13 years, most commonly due to atherosclerosis. HGPS is mainly sporadic in occurrence, but a genetic cause has now been implicated following the identification of de novo heterozygous mutations in the LMNA gene in the majority of HGPS patients.4,5 A single family showing autosomal recessive inheritance of homozygous LMNA mutations has also been reported.6 LMNA encodes lamins A and C, components of the nuclear lamina, a meshwork underlying the nuclear envelope that serves as a structural support and is also thought to contribute to chromatin organisation and the regulation of gene expression.7,8 Interestingly, mutations in LMNA have recently been associated with at least eight inherited disorders, known as laminopathies, with differential dystrophic effects on a variety of tissues including muscle, neurones, skin, bone, and adipose tissue (reviewed in Mounkes et al 9). However, the realisation that these disorders share common genetic defects has led to clinical re-evaluation, with emerging evidence of significant phenotypic overlap.10 Hence the laminopathies might reasonably be considered as a spectrum of related diseases. HGPS has phenotypic similarities to several other laminopathies, in particular the atypical Werner’s syndrome11 and mandibuloacral dysplasia (MAD; OMIM 248370 and 608612).12 These diseases are associated with lipodystrophy,3,13 which is the most prominent feature of another laminopathy, familial partial lipodystrophy of the Dunnigan variety (OMIM 151660).14 MAD has been further classified as two …\",\n \"title\": \"Compound heterozygous ZMPSTE24 mutations reduce prelamin A processing and result in a severe progeroid phenotype.\"\n },\n {\n \"docid\": \"34747208\",\n \"text\": \"Mutations in the nuclear structural protein lamin A cause the premature aging syndrome Hutchinson-Gilford progeria (HGPS). Whether lamin A plays any role in normal aging is unknown. We show that the same molecular mechanism responsible for HGPS is active in healthy cells. Cell nuclei from old individuals acquire defects similar to those of HGPS patient cells, including changes in histone modifications and increased DNA damage. Age-related nuclear defects are caused by sporadic use, in healthy individuals, of the same cryptic splice site in lamin A whose constitutive activation causes HGPS. Inhibition of this splice site reverses the nuclear defects associated with aging. These observations implicate lamin A in physiological aging.\",\n \"title\": \"Lamin A-dependent nuclear defects in human aging.\"\n },\n {\n \"docid\": \"14178995\",\n \"text\": \"The genetic diseases Hutchinson-Gilford progeria syndrome (HGPS) and restrictive dermopathy (RD) arise from accumulation of farnesylated prelamin A because of defects in the lamin A maturation pathway. Both of these diseases exhibit symptoms that can be viewed as accelerated aging. The mechanism by which accumulation of farnesylated prelamin A leads to these accelerated aging phenotypes is not understood. Here we present evidence that in HGPS and RD fibroblasts, DNA damage checkpoints are persistently activated because of the compromise in genomic integrity. Inactivation of checkpoint kinases Ataxia-telangiectasia-mutated (ATM) and ATR (ATM- and Rad3-related) in these patient cells can partially overcome their early replication arrest. Treatment of patient cells with a protein farnesyltransferase inhibitor (FTI) did not result in reduction of DNA double-strand breaks and damage checkpoint signaling, although the treatment significantly reversed the aberrant shape of their nuclei. This suggests that DNA damage accumulation and aberrant nuclear morphology are independent phenotypes arising from prelamin A accumulation in these progeroid syndromes. Since DNA damage accumulation is an important contributor to the symptoms of HGPS, our results call into question the possibility of treatment of HGPS with FTIs alone.\",\n \"title\": \"Summary\"\n },\n {\n \"docid\": \"7468449\",\n \"text\": \"Ever since the first demonstration of their repetitive sequence and unique replication pathway, telomeres have beguiled researchers with how they function in protecting chromosome ends. Of course much has been learned over the years, and we now appreciate that telomeres are comprised of the multimeric protein/DNA shelterin complex and that the formation of t-loops provides protection from DNA damage machinery. Deriving their name from D-loops, t-loops are generated by the insertion of the 3' overhang into telomeric repeats facilitated by the binding of TRF2. Recent studies have uncovered novel forms of chromosome end-structure that may implicate telomere organization in cellular processes beyond its essential role in telomere protection and homeostasis. In particular, we have recently described that t-loops form in a TRF2-dependent manner at interstitial telomere repeat sequences, which we termed interstitial telomere loops (ITLs). These structures are also dependent on association of lamin A/C, a canonical component of the nucleoskeleton that is mutated in myriad human diseases, including human segmental progeroid syndromes. Since ITLs are associated with telomere stability and require functional lamin A/C, our study suggests a mechanistic link between cellular aging (replicative senescence induced by telomere shortening) and organismal aging (modeled by Hutchinson Gilford Progeria Syndrome). Here we speculate on other potential ramifications of ITL formation, from gene expression to genome stability to chromosome structure.\",\n \"title\": \"A beginning of the end: new insights into the functional organization of telomeres\"\n },\n {\n \"docid\": \"31324978\",\n \"text\": \"Progerias are rare genetic diseases characterized by premature aging. Several progeroid disorders are caused by mutations that lead to the accumulation of a lipid-modified (farnesylated) form of prelamin A, a protein that contributes to the structural scaffolding for the cell nucleus. In progeria, the accumulation of farnesyl-prelamin A disrupts this scaffolding, leading to misshapen nuclei. Previous studies have shown that farnesyltransferase inhibitors (FTIs) reverse this cellular abnormality. We tested the efficacy of an FTI (ABT-100) in Zmpste24-deficient mice, a mouse model of progeria. The FTI-treated mice exhibited improved body weight, grip strength, bone integrity, and percent survival at 20 weeks of age. These results suggest that FTIs may have beneficial effects in humans with progeria.\",\n \"title\": \"A protein farnesyltransferase inhibitor ameliorates disease in a mouse model of progeria.\"\n },\n {\n \"docid\": \"7239105\",\n \"text\": \"Remarkable advances have been made in recent years towards therapeutics for cognitive impairment in individuals with Down syndrome (DS) by using mouse models. In this review, we briefly describe the phenotypes of mouse models that represent outcome targets for drug testing, the behavioral tests used to assess impairments in cognition and the known mechanisms of action of several drugs that are being used in preclinical studies or are likely to be tested in clinical trials. Overlaps in the distribution of targets and in the pathways that are affected by these diverse drugs in the trisomic brain suggest new avenues for DS research and drug development.\",\n \"title\": \"The use of mouse models to understand and improve cognitive deficits in Down syndrome\"\n },\n {\n \"docid\": \"38355793\",\n \"text\": \"OBJECTIVE A20 is a TNF-inducible primary response gene, which has been found to have antiapoptotic function in several cancer cells. This study investigates A20 expression in human glioma tissues and four glioma cell lines, and its effect on tumorigenesis of glioma cells and a mouse tumor model. METHODS Human glioma tissue samples and cells were subject to reverse transcription-PCR (RT-PCR), western blotting and immunohistochemistry. Glioma cells was tested by flow cytometry. A xenograft tumor model in mice was utilized to examine the knock-down effect of specific A20 siRNAs on tumorigenesis. RESULTS A20 was overexpressed in clinical glioma tissue samples (63.9%) and correlated with clinical staging. All four human glioma cell lines expressed A20, among which U87 displayed the strongest expression signals. Inhibiting A20 expression by siRNAs in vitro reduced the growth rates of glioma cells and resulted in G1/S arrest and increased apoptosis. In a mouse tumor model, local administration of siRNA significantly suppressed solid tumor growth. CONCLUSIONS A20 was overexpressed both in human glioma tissues and cell lines, and inhibiting A20 expression greatly slowed tumor cell growth in culture and in mice. These findings indicated that A20 is involved in tumorigenesis of human glioma, and may serve as a future therapeutic target.\",\n \"title\": \"A20 is overexpressed in glioma cells and may serve as a potential therapeutic target.\"\n },\n {\n \"docid\": \"31844040\",\n \"text\": \"Two-component systems (TCSs) are widely employed by bacteria to sense specific external signals and conduct an appropriate response via a phosphorylation cascade within the cell. The TCS of the agr operon in the bacterium Staphylococcus aureus forms part of a regulatory process termed quorum sensing, a cell-to-cell communication mechanism used to assess population density. Since S. aureus manipulates this \\\"knowledge\\\" in order to co-ordinate production of its armoury of exotoxin virulence factors required to promote infection, it is important to understand fully how this process works. We present three models of the agr operon, each incorporating a different phosphorylation cascade for the TCS since the precise nature of the cascade is not fully understood. Using numerical and asymptotic techniques we examine the effects of inhibitor therapy, a novel approach to controlling bacterial infection through the attenuation of virulence, on each of these three cascades. We present results which, if evaluated against appropriate experimental data, provide insights into the potential effectiveness of such therapy. Moreover, the TCS models presented here are of broad relevance given that TCSs are widely conserved throughout the bacterial kingdom.\",\n \"title\": \"A mathematical investigation of the effects of inhibitor therapy on three putative phosphorylation cascades governing the two-component system of the agr operon.\"\n },\n {\n \"docid\": \"18414462\",\n \"text\": \"Although the lung is a defining feature of air-breathing animals, the pathway controlling the formation of type I pneumocytes, the cells that mediate gas exchange, is poorly understood. In contrast, the glucocorticoid receptor and its cognate ligand have long been known to promote type II pneumocyte maturation; prenatal administration of glucocorticoids is commonly used to attenuate the severity of infant respiratory distress syndrome (RDS). Here we show that knock-in mutations of the nuclear co-repressor SMRT (silencing mediator of retinoid and thyroid hormone receptors) in C57BL/6 mice (SMRTmRID) produces a previously unidentified respiratory distress syndrome caused by prematurity of the type I pneumocyte. Though unresponsive to glucocorticoids, treatment with anti-thyroid hormone drugs (propylthiouracil or methimazole) completely rescues SMRT-induced RDS, suggesting an unrecognized and essential role for the thyroid hormone receptor (TR) in lung development. We show that TR and SMRT control type I pneumocyte differentiation through Klf2, which, in turn, seems to directly activate the type I pneumocyte gene program. Conversely, mice without lung Klf2 lack mature type I pneumocytes and die shortly after birth, closely recapitulating the SMRTmRID phenotype. These results identify TR as a second nuclear receptor involved in lung development, specifically type I pneumocyte differentiation, and suggest a possible new type of therapeutic option in the treatment of RDS that is unresponsive to glucocorticoids.\",\n \"title\": \"Thyroid Hormone Receptor Repression Linked to Type I Pneumocyte Associated Respiratory Distress Syndrome\"\n },\n {\n \"docid\": \"16232581\",\n \"text\": \"We develop a reversible jump Markov chain Monte Carlo approach to estimating the posterior distribution of phylogenies based on aligned DNA/RNA sequences under several hierarchical evolutionary models. Using a proper, yet nontruncated and uninformative prior, we demonstrate the advantages of the Bayesian approach to hypothesis testing and estimation in phylogenetics by comparing different models for the infinitesimal rates of change among nucleotides, for the number of rate classes, and for the relationships among branch lengths. We compare the relative probabilities of these models and the appropriateness of a molecular clock using Bayes factors. Our most general model, first proposed by Tamura and Nei, parameterizes the infinitesimal change probabilities among nucleotides (A, G, C, T/U) into six parameters, consisting of three parameters for the nucleotide stationary distribution, two rate parameters for nucleotide transitions, and another parameter for nucleotide transversions. Nested models include the Hasegawa, Kishino, and Yano model with equal transition rates and the Kimura model with a uniform stationary distribution and equal transition rates. To illustrate our methods, we examine simulated data, 16S rRNA sequences from 15 contemporary eubacteria, halobacteria, eocytes, and eukaryotes, 9 primates, and the entire HIV genome of 11 isolates. We find that the Kimura model is too restrictive, that the Hasegawa, Kishino, and Yano model can be rejected for some data sets, that there is evidence for more than one rate class and a molecular clock among similar taxa, and that a molecular clock can be rejected for more distantly related taxa.\",\n \"title\": \"Bayesian selection of continuous-time Markov chain evolutionary models.\"\n },\n {\n \"docid\": \"2264455\",\n \"text\": \"There is no licenced vaccine against any human parasitic disease and Plasmodium falciparum malaria, a major cause of infectious mortality, presents a great challenge to vaccine developers. This has led to the assessment of a wide variety of approaches to malaria vaccine design and development, assisted by the availability of a safe challenge model for small-scale efficacy testing of vaccine candidates. Malaria vaccine development has been at the forefront of assessing many new vaccine technologies including novel adjuvants, vectored prime-boost regimes and the concept of community vaccination to block malaria transmission. Most current vaccine candidates target a single stage of the parasite's life cycle and vaccines against the early pre-erythrocytic stages have shown most success. A protein in adjuvant vaccine, working through antibodies against sporozoites, and viral vector vaccines targeting the intracellular liver-stage parasite with cellular immunity show partial efficacy in humans, and the anti-sporozoite vaccine is currently in phase III trials. However, a more effective malaria vaccine suitable for widespread cost-effective deployment is likely to require a multi-component vaccine targeting more than one life cycle stage. The most attractive near-term approach to develop such a product is to combine existing partially effective pre-erythrocytic vaccine candidates.\",\n \"title\": \"Vaccines against malaria\"\n },\n {\n \"docid\": \"33884866\",\n \"text\": \"OBJECTIVE The sphingosine-1-phosphate (S1P) receptor agonist fingolimod (FTY720), that has shown efficacy in advanced multiple sclerosis clinical trials, decreases reperfusion injury in heart, liver, and kidney. We therefore tested the therapeutic effects of fingolimod in several rodent models of focal cerebral ischemia. To assess the translational significance of these findings, we asked whether fingolimod improved long-term behavioral outcomes, whether delayed treatment was still effective, and whether neuroprotection can be obtained in a second species. METHODS We used rodent models of middle cerebral artery occlusion and cell-culture models of neurotoxicity and inflammation to examine the therapeutic potential and mechanisms of neuroprotection by fingolimod. RESULTS In a transient mouse model, fingolimod reduced infarct size, neurological deficit, edema, and the number of dying cells in the core and periinfarct area. Neuroprotection was accompanied by decreased inflammation, as fingolimod-treated mice had fewer activated neutrophils, microglia/macrophages, and intercellular adhesion molecule-1 (ICAM-1)-positive blood vessels. Fingolimod-treated mice showed a smaller infarct and performed better in behavioral tests up to 15 days after ischemia. Reduced infarct was observed in a permanent model even when mice were treated 4 hours after ischemic onset. Fingolimod also decreased infarct size in a rat model of focal ischemia. Fingolimod did not protect primary neurons against glutamate excitotoxicity or hydrogen peroxide, but decreased ICAM-1 expression in brain endothelial cells stimulated by tumor necrosis factor alpha. INTERPRETATION These findings suggest that anti-inflammatory mechanisms, and possibly vasculoprotection, rather than direct effects on neurons, underlie the beneficial effects of fingolimod after stroke. S1P receptors are a highly promising target in stroke treatment.\",\n \"title\": \"Fingolimod provides long-term protection in rodent models of cerebral ischemia.\"\n },\n {\n \"docid\": \"34873974\",\n \"text\": \"OBJECTIVE To obtain summary estimates of the accuracy of a single baseline measurement of the Elecsys Troponin T high-sensitive assay (Roche Diagnostics) for the diagnosis of acute myocardial infarction in patients presenting to the emergency department. DESIGN Systematic review and meta-analysis of diagnostic test accuracy studies. DATA SOURCES Medline, Embase, and other relevant electronic databases were searched for papers published between January 2006 and December 2013. STUDY SELECTION Studies were included if they evaluated the diagnostic accuracy of a single baseline measurement of Elecsys Troponin T high-sensitive assay for the diagnosis of acute myocardial infarction in patients presenting to the emergency department with suspected acute coronary syndrome. STUDY APPRAISAL AND DATA SYNTHESIS The first author screened all titles and abstracts identified through the searches and selected all potentially relevant papers. The screening of the full texts, the data extraction, and the methodological quality assessment, using the adapted QUADAS-2 tool, were conducted independently by two reviewers with disagreements being resolved through discussion or arbitration. If appropriate, meta-analysis was conducted using the hierarchical bivariate model. RESULTS Twenty three studies reported the performance of the evaluated assay at presentation. The results for 14 ng/L and 3-5 ng/L cut-off values were pooled separately. At 14 ng/L (20 papers), the summary sensitivity was 89.5% (95% confidence interval 86.3% to 92.1%) and the summary specificity was 77.1% (68.7% to 83.7%). At 3-5 ng/L (six papers), the summary sensitivity was 97.4% (94.9% to 98.7%) and the summary specificity was 42.4% (31.2% to 54.5%). This means that if 21 of 100 consecutive patients have the target condition (21%, the median prevalence across the studies), 2 (95% confidence interval 2 to 3) of 21 patients with acute myocardial infarction will be missed (false negatives) if 14 ng/L is used as a cut-off value and 18 (13 to 25) of 79 patients without acute myocardial infarction will test positive (false positives). If the 3-5 ng/L cut-off value is used, <1 (0 to 1) patient with acute myocardial infarction will be missed and 46 (36 to 54) patients without acute myocardial infarction will test positive. CONCLUSIONS The results indicate that a single baseline measurement of the Elecsys Troponin T high-sensitive assay could be used to rule out acute myocardial infarction if lower cut-off values such as 3 ng/L or 5 ng/L are used. However, this method should be part of a comprehensive triage strategy and may not be appropriate for patients who present less than three hours after symptom onset. Care must also be exercised because of the higher imprecision of the evaluated assay and the greater effect of lot-to-lot reagent variation at low troponin concentrations. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration number CRD42013003926.\",\n \"title\": \"Diagnostic accuracy of single baseline measurement of Elecsys Troponin T high-sensitive assay for diagnosis of acute myocardial infarction in emergency department: systematic review and meta-analysis\"\n },\n {\n \"docid\": \"24496245\",\n \"text\": \"Genetic evidence implicates the loss of bone morphogenetic protein type II receptor (BMPR-II) signaling in the endothelium as an initiating factor in pulmonary arterial hypertension (PAH). However, selective targeting of this signaling pathway using BMP ligands has not yet been explored as a therapeutic strategy. Here, we identify BMP9 as the preferred ligand for preventing apoptosis and enhancing monolayer integrity in both pulmonary arterial endothelial cells and blood outgrowth endothelial cells from subjects with PAH who bear mutations in the gene encoding BMPR-II, BMPR2. Mice bearing a heterozygous knock-in allele of a human BMPR2 mutation, R899X, which we generated as an animal model of PAH caused by BMPR-II deficiency, spontaneously developed PAH. Administration of BMP9 reversed established PAH in these mice, as well as in two other experimental PAH models, in which PAH develops in response to either monocrotaline or VEGF receptor inhibition combined with chronic hypoxia. These results demonstrate the promise of direct enhancement of endothelial BMP signaling as a new therapeutic strategy for PAH.\",\n \"title\": \"Selective enhancement of endothelial BMPR-II with BMP9 reverses pulmonary arterial hypertension\"\n },\n {\n \"docid\": \"7317051\",\n \"text\": \"Pancreatic ductal adenocarcinoma (PDA) represents an unmet therapeutic challenge. PDA is addicted to the activity of the mutated KRAS oncogene which is considered so far an undruggable therapeutic target. We propose an approach to target KRAS effectively in patients using RNA interference. To meet this challenge, we have developed a local prolonged siRNA delivery system (Local Drug EluteR, LODER) shedding siRNA against the mutated KRAS (siG12D LODER). The siG12D LODER was assessed for its structural, release, and delivery properties in vitro and in vivo. The effect of the siG12D LODER on tumor growth was assessed in s.c. and orthotopic mouse models. KRAS silencing effect was further assessed on the KRAS downstream signaling pathway. The LODER-encapsulated siRNA was stable and active in vivo for 155 d. Treatment of PDA cells with siG12D LODER resulted in a significant decrease in KRAS levels, leading to inhibition of proliferation and epithelial-mesenchymal transition. In vivo, siG12D LODER impeded the growth of human pancreatic tumor cells and prolonged mouse survival. We report a reproducible and safe delivery platform based on a miniature biodegradable polymeric matrix, for the controlled and prolonged delivery of siRNA. This technology provides the following advantages: (i) siRNA is protected from degradation; (ii) the siRNA is slowly released locally within the tumor for prolonged periods; and (iii) the siG12D LODER elicits a therapeutic effect, thereby demonstrating that mutated KRAS is indeed a druggable target.\",\n \"title\": \"Mutant KRAS is a druggable target for pancreatic cancer.\"\n },\n {\n \"docid\": \"14116046\",\n \"text\": \"Retinoic acid-related orphan receptors RORα and RORγ play a regulatory role in lipid/glucose homeostasis and various immune functions, and have been implicated in metabolic syndrome and several inflammatory diseases. RORα-deficient mice are protected against age- and diet-induced obesity, hepatosteatosis, and insulin resistance. The resistance to hepatosteatosis in RORα-deficient mice is related to the reduced expression of several genes regulating lipid synthesis, transport, and storage. Adipose tissue-associated inflammation, which plays a critical role in the development of insulin resistance, is considerably diminished in RORα-deficient mice as indicated by the reduced infiltration of M1 macrophages and decreased expression of many proinflammatory genes. Deficiency in RORγ also protects against diet-induced insulin resistance by a mechanism that appears different from that in RORα deficiency. Recent studies indicated that RORs provide an important link between the circadian clock machinery and its regulation of metabolic genes and metabolic syndrome. As ligand-dependent transcription factors, RORs may provide novel therapeutic targets in the management of obesity and associated metabolic diseases, including hepatosteatosis, adipose tissue-associated inflammation, and insulin resistance.\",\n \"title\": \"Retinoic acid-related orphan receptors α and γ: key regulators of lipid/glucose metabolism, inflammation, and insulin sensitivity\"\n },\n {\n \"docid\": \"2837758\",\n \"text\": \"Epitope vaccine is a promising option for therapeutic vaccination against Helicobacter pylori (H. pylori) infection. In this study, we constructed a multi-epitope vaccine with five epitopes and mucosal adjuvant E. coli heat-labile enterotoxin B subunit (LTB) named HUepi-LTB and evaluated its therapeutic effect against H. pylori infection in BALB/c mice model. HUepi-LTB containing three Th epitopes from UreB and two B cell epitopes from UreB and HpaA was constructed and expressed in E. coli. Oral therapeutic immunization with HUepi-LTB significantly decreased H. pylori colonization compared with oral immunization with PBS, and the protection was correlated with antigen-specific CD4+ T cells and IgG and mucosal IgA antibody responses. This multi-epitope vaccine may be a promising vaccine candidate that may help to control H. pylori infection.\",\n \"title\": \"Therapeutic efficacy of a multi-epitope vaccine against Helicobacter pylori infection in BALB/c mice model.\"\n },\n {\n \"docid\": \"8690595\",\n \"text\": \"Although genetic association studies have been with us for many years, even for the simplest analyses there is little consensus on the most appropriate statistical procedures. Here I give an overview of statistical approaches to population association studies, including preliminary analyses (Hardy–Weinberg equilibrium testing, inference of phase and missing data, and SNP tagging), and single-SNP and multipoint tests for association. My goal is to outline the key methods with a brief discussion of problems (population structure and multiple testing), avenues for solutions and some ongoing developments.\",\n \"title\": \"A tutorial on statistical methods for population association studies\"\n },\n {\n \"docid\": \"878526\",\n \"text\": \"Despite progress in the development of drugs that efficiently target cancer cells, treatments for metastatic tumours are often ineffective. The now well-established dependency of cancer cells on their microenvironment suggests that targeting the non-cancer-cell component of the tumour might form a basis for the development of novel therapeutic approaches. However, the as-yet poorly characterized contribution of host responses during tumour growth and metastatic progression represents a limitation to exploiting this approach. Here we identify neutrophils as the main component and driver of metastatic establishment within the (pre-)metastatic lung microenvironment in mouse breast cancer models. Neutrophils have a fundamental role in inflammatory responses and their contribution to tumorigenesis is still controversial. Using various strategies to block neutrophil recruitment to the pre-metastatic site, we demonstrate that neutrophils specifically support metastatic initiation. Importantly, we find that neutrophil-derived leukotrienes aid the colonization of distant tissues by selectively expanding the sub-pool of cancer cells that retain high tumorigenic potential. Genetic or pharmacological inhibition of the leukotriene-generating enzyme arachidonate 5-lipoxygenase (Alox5) abrogates neutrophil pro-metastatic activity and consequently reduces metastasis. Our results reveal the efficacy of using targeted therapy against a specific tumour microenvironment component and indicate that neutrophil Alox5 inhibition may limit metastatic progression.\",\n \"title\": \"Neutrophils support lung colonization of metastasis-initiating breast cancer cells\"\n },\n {\n \"docid\": \"20372201\",\n \"text\": \"A growing body of evidence supports the notion that malignant tumors are heterogeneous and contain diverse subpopulations of cells with unique characteristics including the ability to initiate a tumor and metastasize. This phenomenon might be explained by the so-called cancer stem cell (CSC) theory. Recent technological developments have allowed a deeper understanding and characterization of CSCs. Even though the application of this theory to hematopoietic malignancies and solid tumors holds promise for new ways to treat cancer, it also brings some skepticism. Efficacious therapeutic approaches targeting the CSC population should be explored to overcome therapeutic failure and improve patient outcomes. This review will focus on the intrinsic and extrinsic regulation of CSCs, as well as the development of therapeutic approaches against CSCs, predominantly focusing on gastrointestinal malignancies.\",\n \"title\": \"Cancer stem cell theory in gastrointestinal malignancies: recent progress and upcoming challenges\"\n },\n {\n \"docid\": \"4544916\",\n \"text\": \"To efficiently counteract pathogens, plants rely on a complex set of immune responses that are tightly regulated to allow the timely activation, appropriate duration and adequate amplitude of defense programs. The coordination of the plant immune response is known to require the activity of the ubiquitin/proteasome system, which controls the stability of proteins in eukaryotes. Here, we demonstrate that the N-end rule pathway, a subset of the ubiquitin/proteasome system, regulates the defense against a wide range of bacterial and fungal pathogens in the model plant Arabidopsis thaliana. We show that this pathway positively regulates the biosynthesis of plant-defense metabolites such as glucosinolates, as well as the biosynthesis and response to the phytohormone jasmonic acid, which plays a key role in plant immunity. Our results also suggest that the arginylation branch of the N-end rule pathway regulates the timing and amplitude of the defense program against the model pathogen Pseudomonas syringae AvrRpm1.\",\n \"title\": \"The N-end rule pathway regulates pathogen responses in plants.\"\n },\n {\n \"docid\": \"17682477\",\n \"text\": \"To test the feasibility of a single T-cell manipulation to eliminate alloreactivity while sparing antiviral and antitumor T cells, we infused 12 haploidentical hematopoietic stem cell transplant patients with increasing numbers of alloreplete haploidentical T cells expressing the inducible caspase 9 suicide gene (iC9-T cells). We determined whether the iC9-T cells produced immune reconstitution and if any resultant graft-versus-host disease (GVHD) could be controlled by administration of a chemical inducer of dimerization (CID; AP1903/Rimiducid). All patients receiving >10(4) alloreplete iC9-T lymphocytes per kilogram achieved rapid reconstitution of immune responses toward 5 major pathogenic viruses and concomitant control of active infections. Four patients received a single AP1903 dose. CID infusion eliminated 85% to 95% of circulating CD3(+)CD19(+) T cells within 30 minutes, with no recurrence of GVHD within 90 days. In one patient, symptoms and signs of GVHD-associated cytokine release syndrome (CRS-hyperpyrexia, high levels of proinflammatory cytokines, and rash) resolved within 2 hours of AP1903 infusion. One patient with varicella zoster virus meningitis and acute GVHD had iC9-T cells present in the cerebrospinal fluid, which were reduced by >90% after CID. Notably, virus-specific T cells recovered even after AP1903 administration and continued to protect against infection. Hence, alloreplete iC9-T cells can reconstitute immunity posttransplant and administration of CID can eliminate them from both peripheral blood and the central nervous system (CNS), leading to rapid resolution of GVHD and CRS. The approach may therefore be useful for the rapid and effective treatment of toxicities associated with infusion of engineered T lymphocytes. This trial was registered at www.clinicaltrials.gov as #NCT01494103.\",\n \"title\": \"Inducible caspase-9 suicide gene controls adverse effects from alloreplete T cells after haploidentical stem cell transplantation.\"\n },\n {\n \"docid\": \"44827480\",\n \"text\": \"BACKGROUND Few data exist about the implementation of contemporary oral antiplatelet treatment guidelines in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). METHODS GReek AntiPlatelet rEgistry (GRAPE), initiated on January 2012, is a prospective, observational, multicenter cohort study focusing on contemporary use of P2Y12 inhibitors. In 1434 patients we evaluated appropriateness of P2Y12 selection initially and at discharge by applying an eligibility-assessing algorithm based on P2Y12 inhibitors' contraindications/specific warnings and precautions. RESULTS Appropriate, less preferable and inappropriate P2Y12 inhibitor selections were made initially in 45.8%, 47.2% and 6.6% and at discharge in 64.1%, 29.2% and 6.6% of patients, respectively. The selection of clopidogrel was most commonly less preferable, both initially (69.7%) and at discharge (75.6%). Appropriate selection of newer agents was high initially (79.2%-82.8%), with further increase as selection at discharge (89.4%-89.8%). Inappropriate selection of the newer agents was 17.2%-20.8% initially, decreasing to 10.2%-10.6% at discharge. Conditions and co-medications related to increased bleeding risk, presentation with ST elevation myocardial infarction and the absence of reperfusion within the first 24h were the most powerful predictors of appropriate P2Y12 selection initially, whereas age ≥75 years, conditions and co-medications related to increased bleeding risk and regional trends mostly affected appropriate P2Y12 selection at discharge. CONCLUSIONS In GRAPE, adherence with the recently released guidelines on oral antiplatelet therapy was satisfactory. Clopidogrel was most commonly used as a less preferable selection, while prasugrel or ticagrelor selection was mostly appropriate. Certain factors may predict initial and at discharge guideline implementation. Clinical Trial Registration-clinicaltrials.gov Identifier: NCT01774955 http://clinicaltrials.gov/.\",\n \"title\": \"Implementation of contemporary oral antiplatelet treatment guidelines in patients with acute coronary syndrome undergoing percutaneous coronary intervention: a report from the GReek AntiPlatelet rEgistry (GRAPE).\"\n },\n {\n \"docid\": \"8133050\",\n \"text\": \"Many microparasites infect new hosts with specialized life stages, requiring a subset of the parasite population to forgo proliferation and develop into transmission forms. Transmission stage production influences infectivity, host exploitation, and the impact of medical interventions like drug treatment. Predicting how parasites will respond to public health efforts on both epidemiological and evolutionary timescales requires understanding transmission strategies. These strategies can rarely be observed directly and must typically be inferred from infection dynamics. Using malaria as a case study, we test previously described methods for inferring transmission stage investment against simulated data generated with a model of within-host infection dynamics, where the true transmission investment is known. We show that existing methods are inadequate and potentially very misleading. The key difficulty lies in separating transmission stages produced by different generations of parasites. We develop a new approach that performs much better on simulated data. Applying this approach to real data from mice infected with a single Plasmodium chabaudi strain, we estimate that transmission investment varies from zero to 20%, with evidence for variable investment over time in some hosts, but not others. These patterns suggest that, even in experimental infections where host genetics and other environmental factors are controlled, parasites may exhibit remarkably different patterns of transmission investment.\",\n \"title\": \"Quantifying Transmission Investment in Malaria Parasites\"\n },\n {\n \"docid\": \"12030735\",\n \"text\": \"OBJECTIVE Limited information is available about the metabolic syndrome in Asians. Furthermore, the definition of central obesity using waist circumference may not be appropriate for Asians. The objectives of this study were to determine the optimal waist circumference for diagnosing central obesity in Asians and to estimate the prevalence of the metabolic syndrome in an Asian population. RESEARCH DESIGN AND METHODS We used data from the 1998 Singapore National Health Survey, a cross-sectional survey involving 4,723 men and women of Chinese, Malay, and Asian-Indian ethnicity aged 18-69 years. Receiver operating characteristic analysis suggested that waist circumference >80 cm in women and >90 cm in men was a more appropriate definition of central obesity in this population. The prevalence of the metabolic syndrome was then determined using the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria with and without the modified waist circumference criteria. RESULTS In Asians, decreasing waist circumference increased the crude prevalence of the metabolic syndrome from 12.2 to 17.9%. Using the modified Asian criteria, the prevalence of the metabolic syndrome increased from 2.9% in those aged 18-30 years to 31.0% in those aged 60-69 years. It was more common in men (prevalence 20.9% in men versus 15.5% in women; P < 0.001) and Asian Indians (prevalence 28.8% in Asian-Indians, 24.2% in Malays, and 14.8% in Chinese; P < 0.001). CONCLUSIONS NCEP ATP III criteria, applied to an Asian population, will underestimate the population at risk. With a lower waist circumference cutoff, the prevalence of the metabolic syndrome is comparable to that in Western populations. Ethnic differences are likely to exist between populations across Asia.\",\n \"title\": \"Can we apply the National Cholesterol Education Program Adult Treatment Panel definition of the metabolic syndrome to Asians?\"\n },\n {\n \"docid\": \"28017005\",\n \"text\": \"Assessment for selection in medicine and the health professions should follow the same quality assurance processes as in-course assessment. The literature on selection is limited and is not strongly theoretical or conceptual. For written testing, there is evidence of the predictive validity of Medical College Admission Test (MCAT) for medical school and licensing examination performance. There is also evidence for the predictive validity of grade point average, particularly in combination with MCAT for graduate entry but little evidence about the predictive validity of school leaver scores. Interviews have not been shown to be robust selection measures. Studies of multiple mini-interviews have indicated good predictive validity and reliability. Of other measures used in selection, only the growing interest in personality testing appears to warrant future work. Widening access to medical and health professional programmes is an increasing priority and relates to the social accountability mandate of medical and health professional schools. While traditional selection measures do discriminate against various population groups, there is little evidence on the effect of non-traditional measures in widening access. Preparation and outreach programmes show most promise. In summary, the areas of consensus for assessment for selection are small in number. Recommendations for future action focus on the adoption of principles of good assessment and curriculum alignment, use of multi-method programmatic approaches, development of interdisciplinary frameworks and utilisation of sophisticated measurement models. The social accountability mandate of medical and health professional schools demands that social inclusion, workforce issues and widening of access are embedded in the principles of good assessment for selection.\",\n \"title\": \"Assessment for selection for the health care professions and specialty training: consensus statement and recommendations from the Ottawa 2010 Conference.\"\n },\n {\n \"docid\": \"13965483\",\n \"text\": \"Epitope vaccine based on the enzyme urease of Helicobacter pylori is a promising option for prophylactic and therapeutic vaccination against H. pylori infection. In our previous study, the epitope vaccine CTB-UA, which was composed of the mucosal adjuvant cholera toxin B subunit (CTB) and an epitope (UreA183–203) from the H. pylori urease A subunit (UreA) was constructed. This particular vaccine was shown to have good immunogenicity and immunoreactivity and could induce specific neutralizing antibodies, which exhibited effectively inhibitory effects on the enzymatic activity of H. pylori urease. In this study, the prophylactic and therapeutic efficacy of the epitope vaccine CTB-UA was evaluated in a BALB/c mice model. The experimental results indicated that oral prophylactic or therapeutic immunization with CTB-UA significantly decreased H. pylori colonization compared with oral immunization with PBS. The results also revealed that the protection was correlated with antigen-specific IgG, IgA, and mucosal secretory IgA antibody responses. CTB-UA may be a promising vaccine candidate for the control of H. pylori infection.\",\n \"title\": \"Prophylactic and therapeutic efficacy of the epitope vaccine CTB-UA against Helicobacter pylori infection in a BALB/c mice model\"\n },\n {\n \"docid\": \"1967410\",\n \"text\": \"Although significant progress has occurred in the past 20 years regarding our understanding of Alzheimer disease pathogenesis, we have yet to identify disease-modifying therapeutics capable of substantially altering the clinical course of this prevalent neurodegenerative disease. In this short review, we discuss 2 approaches that are currently being tested clinically (γ-secretase inhibition and γ-secretase modulation) and emphasize the significant differences between these 2 therapeutic approaches. We also discuss certain genetic- and biomarker-based translational and clinical trial paradigms that may assist in developing a useful therapeutic agent.\",\n \"title\": \"Potential use of γ-secretase modulators in the treatment of Alzheimer disease.\"\n },\n {\n \"docid\": \"16605494\",\n \"text\": \"BACKGROUND Whereas many causes and mechanisms of neurodegenerative diseases have been identified, very few therapeutic strategies have emerged in parallel. One possible explanation is that successful treatment strategy may require simultaneous targeting of more than one molecule of pathway. A new therapeutic approach to have emerged recently is the engagement of microRNAs (miRNAs), which affords the opportunity to target multiple cellular pathways simultaneously using a single sequence. METHODOLOGY/PRINCIPAL FINDINGS We identified miR-22 as a potentially neuroprotective miRNA based on its predicted regulation of several targets implicated in Huntington's disease (histone deacetylase 4 (HDAC4), REST corepresor 1 (Rcor1) and regulator of G-protein signaling 2 (Rgs2)) and its diminished expression in Huntington's and Alzheimer's disease brains. We then tested the hypothesis that increasing cellular levels of miRNA-22 would achieve neuroprotection in in vitro models of neurodegeneration. As predicted, overexpression of miR-22 inhibited neurodegeneration in primary striatal and cortical cultures exposed to a mutated human huntingtin fragment (Htt171-82Q). Overexpression of miR-22 also decreased neurodegeneration in primary neuronal cultures exposed to 3-nitropropionic acid (3-NP), a mitochondrial complex II/III inhibitor. In addition, miR-22 improved neuronal viability in an in vitro model of brain aging. The mechanisms underlying the effects of miR-22 included a reduction in caspase activation, consistent with miR-22's targeting the pro-apoptotic activities of mitogen-activated protein kinase 14/p38 (MAPK14/p38) and tumor protein p53-inducible nuclear protein 1 (Tp53inp1). Moreover, HD-specific effects comprised not only targeting HDAC4, Rcor1 and Rgs2 mRNAs, but also decreasing focal accumulation of mutant Htt-positive foci, which occurred via an unknown mechanism. CONCLUSIONS These data show that miR-22 has multipartite anti-neurodegenerative activities including the inhibition of apoptosis and the targeting of mRNAs implicated in the etiology of HD. These results motivate additional studies to evaluate the feasibility and therapeutic efficacy of manipulating miR-22 in vivo.\",\n \"title\": \"MicroRNA-22 (miR-22) Overexpression Is Neuroprotective via General Anti-Apoptotic Effects and May also Target Specific Huntington’s Disease-Related Mechanisms\"\n }\n]"}}},{"rowIdx":192,"cells":{"query_id":{"kind":"string","value":"564"},"query":{"kind":"string","value":"In British Men, haplogroup I increases risk of cardiovascular disease by 50%."},"positive_passages":{"kind":"list like","value":[{"docid":"2867345","text":"BACKGROUND A sexual dimorphism exists in the incidence and prevalence of coronary artery disease--men are more commonly affected than are age-matched women. We explored the role of the Y chromosome in coronary artery disease in the context of this sexual inequity. METHODS We genotyped 11 markers of the male-specific region of the Y chromosome in 3233 biologically unrelated British men from three cohorts: the British Heart Foundation Family Heart Study (BHF-FHS), West of Scotland Coronary Prevention Study (WOSCOPS), and Cardiogenics Study. On the basis of this information, each Y chromosome was tracked back into one of 13 ancient lineages defined as haplogroups. We then examined associations between common Y chromosome haplogroups and the risk of coronary artery disease in cross-sectional BHF-FHS and prospective WOSCOPS. Finally, we undertook functional analysis of Y chromosome effects on monocyte and macrophage transcriptome in British men from the Cardiogenics Study. FINDINGS Of nine haplogroups identified, two (R1b1b2 and I) accounted for roughly 90% of the Y chromosome variants among British men. Carriers of haplogroup I had about a 50% higher age-adjusted risk of coronary artery disease than did men with other Y chromosome lineages in BHF-FHS (odds ratio 1·75, 95% CI 1·20-2·54, p=0·004), WOSCOPS (1·45, 1·08-1·95, p=0·012), and joint analysis of both populations (1·56, 1·24-1·97, p=0·0002). The association between haplogroup I and increased risk of coronary artery disease was independent of traditional cardiovascular and socioeconomic risk factors. Analysis of macrophage transcriptome in the Cardiogenics Study revealed that 19 molecular pathways showing strong differential expression between men with haplogroup I and other lineages of the Y chromosome were interconnected by common genes related to inflammation and immunity, and that some of them have a strong relevance to atherosclerosis. INTERPRETATION The human Y chromosome is associated with risk of coronary artery disease in men of European ancestry, possibly through interactions of immunity and inflammation. FUNDING British Heart Foundation; UK National Institute for Health Research; LEW Carty Charitable Fund; National Health and Medical Research Council of Australia; European Union 6th Framework Programme; Wellcome Trust.","title":"Inheritance of coronary artery disease in men: an analysis of the role of the Y chromosome"}],"string":"[\n {\n \"docid\": \"2867345\",\n \"text\": \"BACKGROUND A sexual dimorphism exists in the incidence and prevalence of coronary artery disease--men are more commonly affected than are age-matched women. We explored the role of the Y chromosome in coronary artery disease in the context of this sexual inequity. METHODS We genotyped 11 markers of the male-specific region of the Y chromosome in 3233 biologically unrelated British men from three cohorts: the British Heart Foundation Family Heart Study (BHF-FHS), West of Scotland Coronary Prevention Study (WOSCOPS), and Cardiogenics Study. On the basis of this information, each Y chromosome was tracked back into one of 13 ancient lineages defined as haplogroups. We then examined associations between common Y chromosome haplogroups and the risk of coronary artery disease in cross-sectional BHF-FHS and prospective WOSCOPS. Finally, we undertook functional analysis of Y chromosome effects on monocyte and macrophage transcriptome in British men from the Cardiogenics Study. FINDINGS Of nine haplogroups identified, two (R1b1b2 and I) accounted for roughly 90% of the Y chromosome variants among British men. Carriers of haplogroup I had about a 50% higher age-adjusted risk of coronary artery disease than did men with other Y chromosome lineages in BHF-FHS (odds ratio 1·75, 95% CI 1·20-2·54, p=0·004), WOSCOPS (1·45, 1·08-1·95, p=0·012), and joint analysis of both populations (1·56, 1·24-1·97, p=0·0002). The association between haplogroup I and increased risk of coronary artery disease was independent of traditional cardiovascular and socioeconomic risk factors. Analysis of macrophage transcriptome in the Cardiogenics Study revealed that 19 molecular pathways showing strong differential expression between men with haplogroup I and other lineages of the Y chromosome were interconnected by common genes related to inflammation and immunity, and that some of them have a strong relevance to atherosclerosis. INTERPRETATION The human Y chromosome is associated with risk of coronary artery disease in men of European ancestry, possibly through interactions of immunity and inflammation. FUNDING British Heart Foundation; UK National Institute for Health Research; LEW Carty Charitable Fund; National Health and Medical Research Council of Australia; European Union 6th Framework Programme; Wellcome Trust.\",\n \"title\": \"Inheritance of coronary artery disease in men: an analysis of the role of the Y chromosome\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"29253460","text":"OBJECTIVE To assess whether sex differences exist in the angiographic severity, management and outcomes of acute coronary syndromes (ACS). METHODS The study comprised 7638 women and 19 117 men with ACS who underwent coronary angiography and were included in GRACE (Global Registry of Acute Coronary Events) from 1999-2006. Normal vessels/mild disease was defined as <50% stenosis in all epicardial vessels; advanced disease was defined as >or=one vessel with >or=50% stenosis. RESULTS Women were older than men and had higher rates of cardiovascular risk factors. Men and women presented equally with chest pain; however, jaw pain and nausea were more frequent among women. Women were more likely to have normal/mild disease (12% vs 6%, p<0.001) and less likely to have left-main and three-vessel disease (27% vs 32%, p<0.001) or undergo percutaneous coronary intervention (65% vs 68%, p<0.001). Women and men with normal and mild disease were treated less aggressively than those with advanced disease. Women with advanced disease had a higher risk of death (4% vs 3%, p<0.01). After adjustment for age and extent of disease, women were more likely to have adverse outcomes (death, myocardial infarction, stroke and rehospitalisation) at six months compared to men (odds ratio 1.24, 95% confidence interval 1.14 to 1.34); however, sex differences in mortality were no longer statistically significant. CONCLUSIONS Women with ACS were more likely to have cardiovascular disease risk factors and atypical symptoms such as nausea compared with men, but were more likely to have normal/mild angiographic coronary artery disease. Further study regarding sex differences related to disease severity is warranted.","title":"Sex-related differences in the presentation, treatment and outcomes among patients with acute coronary syndromes: the Global Registry of Acute Coronary Events."},{"docid":"5698494","text":"OBJECTIVES To investigate whether statins reduce all cause mortality and major coronary and cerebrovascular events in people without established cardiovascular disease but with cardiovascular risk factors, and whether these effects are similar in men and women, in young and older (>65 years) people, and in people with diabetes mellitus. DESIGN Meta-analysis of randomised trials. DATA SOURCES Cochrane controlled trials register, Embase, and Medline. Data abstraction Two independent investigators identified studies on the clinical effects of statins compared with a placebo or control group and with follow-up of at least one year, at least 80% or more participants without established cardiovascular disease, and outcome data on mortality and major cardiovascular disease events. Heterogeneity was assessed using the Q and I(2) statistics. Publication bias was assessed by visual examination of funnel plots and the Egger regression test. RESULTS 10 trials enrolled a total of 70 388 people, of whom 23 681 (34%) were women and 16 078 (23%) had diabetes mellitus. Mean follow-up was 4.1 years. Treatment with statins significantly reduced the risk of all cause mortality (odds ratio 0.88, 95% confidence interval 0.81 to 0.96), major coronary events (0.70, 0.61 to 0.81), and major cerebrovascular events (0.81, 0.71 to 0.93). No evidence of an increased risk of cancer was observed. There was no significant heterogeneity of the treatment effect in clinical subgroups. CONCLUSION In patients without established cardiovascular disease but with cardiovascular risk factors, statin use was associated with significantly improved survival and large reductions in the risk of major cardiovascular events.","title":"The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials"},{"docid":"12770738","text":"BACKGROUND Questions remain as to whether higher levels of cardiorespiratory fitness, a measure of regular physical activity, are associated with lower risk of cardiovascular disease (CVD) mortality in overweight and obese individuals with diabetes. Our objective was to quantify the independent and joint relations of cardiorespiratory fitness (hereafter, fitness) and body mass index (BMI; calculated as weight in kilograms divided by the square of height in meters) with CVD mortality in men with diabetes. METHODS This study was conducted using prospective observational data from the Aerobics Center Longitudinal Study. Study participants comprised 2316 men with no history of stroke or myocardial infarction and who were diagnosed as having diabetes (mean [SD] age, 50 [10] years); had a medical examination, including a maximal exercise test during 1970 to 1997 with mortality surveillance to December 31, 1998; and had a BMI of 18.5 or greater and less than 35.0. The main outcome measure was CVD mortality across levels of fitness with stratification by BMI. RESULTS We identified 179 CVD deaths during a mean (SD) follow-up of 15.9 (7.9) years and 36,710 man-years of exposure. In a model containing age, examination year, fasting glucose level, systolic blood pressure, parental history of premature CVD, total cholesterol level, cigarette smoking, abnormal resting, and exercise electrocardiograms, a significantly higher adjusted risk of mortality was observed in men with a low fitness level who were normal weight (hazard ratio, 2.7 [95% confidence interval, 1.3-5.7]), overweight (hazard ratio, 2.7 [95% confidence interval, 1.4-5.1]), and class 1 obese (hazard ratio, 2.8 [95% confidence interval, 1.4-5.1]) compared with normal weight men with a high fitness level. CONCLUSION In this cohort of men with diabetes, low fitness level was associated with increased risk of CVD mortality within normal weight, overweight, and class 1 obese weight categories.","title":"Cardiorespiratory fitness and body mass index as predictors of cardiovascular disease mortality among men with diabetes."},{"docid":"8780599","text":"OBJECTIVE Although the Polypill concept (proposed in 2003) is promising in terms of benefits for cardiovascular risk management, the potential costs and adverse effects are its main pitfalls. The objective of this study was to identify a tastier and safer alternative to the Polypill: the Polymeal. METHODS Data on the ingredients of the Polymeal were taken from the literature. The evidence based recipe included wine, fish, dark chocolate, fruits, vegetables, garlic, and almonds. Data from the Framingham heart study and the Framingham offspring study were used to build life tables to model the benefits of the Polymeal in the general population from age 50, assuming multiplicative correlations. RESULTS Combining the ingredients of the Polymeal would reduce cardiovascular disease events by 76%. For men, taking the Polymeal daily represented an increase in total life expectancy of 6.6 years, an increase in life expectancy free from cardiovascular disease of 9.0 years, and a decrease in life expectancy with cardiovascular disease of 2.4 years. The corresponding differences for women were 4.8, 8.1, and 3.3 years. CONCLUSION The Polymeal promises to be an effective, non-pharmacological, safe, cheap, and tasty alternative to reduce cardiovascular morbidity and increase life expectancy in the general population.","title":"The Polymeal: a more natural, safer, and probably tastier (than the Polypill) strategy to reduce cardiovascular disease by more than 75%."},{"docid":"21003930","text":"BACKGROUND Long-term exposure to pollution can lead to an increase in the rate of decline of lung function, especially in older individuals and in those with chronic obstructive pulmonary disease (COPD), whereas shorter-term exposure at higher pollution levels has been implicated in causing excess deaths from ischaemic heart disease and exacerbations of COPD. We aimed to assess the effects on respiratory and cardiovascular responses of walking down a busy street with high levels of pollution compared with walking in a traffic-free area with lower pollution levels in older adults. METHODS In this randomised, crossover study, we recruited men and women aged 60 years and older with angiographically proven stable ischaemic heart disease or stage 2 Global initiative for Obstructive Lung Disease (GOLD) COPD who had been clinically stable for 6 months, and age-matched healthy volunteers. Individuals with ischaemic heart disease or COPD were recruited from existing databases or outpatient respiratory and cardiology clinics at the Royal Brompton & Harefield NHS Foundation Trust and age-matched healthy volunteers using advertising and existing databases. All participants had abstained from smoking for at least 12 months and medications were taken as recommended by participants' doctors during the study. Participants were randomly assigned by drawing numbered disks at random from a bag to do a 2 h walk either along a commercial street in London (Oxford Street) or in an urban park (Hyde Park). Baseline measurements of participants were taken before the walk in the hospital laboratory. During each walk session, black carbon, particulate matter (PM) concentrations, ultrafine particles, and nitrogen dioxide (NO2) concentrations were measured. FINDINGS Between October, 2012, and June, 2014, we screened 135 participants, of whom 40 healthy volunteers, 40 individuals with COPD, and 39 with ischaemic heart disease were recruited. Concentrations of black carbon, NO2, PM10, PM2.5, and ultrafine particles were higher on Oxford Street than in Hyde Park. Participants with COPD reported more cough (odds ratio [OR] 1·95, 95% CI 0·96-3·95; p<0·1), sputum (3·15, 1·39-7·13; p<0·05), shortness of breath (1·86, 0·97-3·57; p<0·1), and wheeze (4·00, 1·52-10·50; p<0·05) after walking down Oxford Street compared with Hyde Park. In all participants, irrespective of their disease status, walking in Hyde Park led to an increase in lung function (forced expiratory volume in the first second [FEV1] and forced vital capacity [FVC]) and a decrease in pulse wave velocity (PWV) and augmentation index up to 26 h after the walk. By contrast, these beneficial responses were attenuated after walking on Oxford Street. In participants with COPD, a reduction in FEV1 and FVC, and an increase in R5-20 were associated with an increase in during-walk exposure to NO2, ultrafine particles and PM2.5, and an increase in PWV and augmentation index with NO2 and ultrafine particles. In healthy volunteers, PWV and augmentation index were associated both with black carbon and ultrafine particles. INTERPRETATION Short-term exposure to traffic pollution prevents the beneficial cardiopulmonary effects of walking in people with COPD, ischaemic heart disease, and those free from chronic cardiopulmonary diseases. Medication use might reduce the adverse effects of air pollution in individuals with ischaemic heart disease. Policies should aim to control ambient levels of air pollution along busy streets in view of these negative health effects. FUNDING British Heart Foundation.","title":"Respiratory and cardiovascular responses to walking down a traffic-polluted road compared with walking in a traffic-free area in participants aged 60 years and older with chronic lung or heart disease and age-matched healthy controls: a randomised, crossover study"},{"docid":"39368721","text":"OBJECTIVE to investigate the role of glucose tolerance in the development of hypertension. DESIGN Retrospective analysis of the results of a health check up in a group of clinically healthy middle aged men in the late 1960s (median year 1968). The subjects were invited to enter into a primary prevention trial for cardiovascular disease in 1974, when they underwent clinical examination for risk factors. The trial was completed in 1979, when the men were re-examined. Follow up was in 1986. SETTING Institute of Occupational Health, Helsinki, Finland and second department of medicine, University of Helsinki. SUBJECTS In all, 3490 men born during 1919-34 participated in a health check up in the late 1960s. In 1974, 1815 of these men who were clinically healthy were entered into a primary prevention trial for cardiovascular disease. On clinical examination 1222 of the men were considered at high risk of cardiovascular disease. Of these, 612 received an intervention and were excluded from the study. A total of 593 men were without risk factors. The study comprised all of the men who did not have an intervention (n = 1203). In 1979, 1120 men were re-examined, and in 1986 945 men attended follow up. There were two groups for analysis: one comprising all subjects and the other comprising only men who were normotensive in 1968 and for whom complete information was available. INTERVENTIONS By 1979, 103 men were taking antihypertensive drugs, and by 1986, 131 were taking antihypertensive drugs and 12 were taking drugs for hyperglycaemia. MAIN OUTCOME MEASURES Blood glucose concentration one hour after a glucose load, blood pressure, and body weight were measured in 1968, 1974, and 1979. In 1986 blood pressure and body weight were recorded. RESULTS Men who were hypertensive in 1986 had significantly higher blood pressures (p less than 0.0001) and (after adjustment for body mass index and alcohol intake) significantly higher blood glucose concentrations one hour after a glucose load at all examinations than those who were normotensive in 1986. Regression analysis showed that the higher the blood glucose concentration after a glucose load in 1968 the higher the blood pressure during the following years. Those men between the second and third tertiles of blood glucose concentration in 1968 had a significantly higher risk of developing hypertension (odds ratio 1.71, 95% confidence interval 1.05 to 2.77) compared with those below the first tertile. CONCLUSION In this study men who developed hypertension tended to have shown an increased intolerance to glucose up to 18 years before the clinical manifestation of their disorder. Blood glucose concentration one hour after a glucose load was an independent predictor of future hypertension.","title":"Glucose tolerance and blood pressure: long term follow up in middle aged men."},{"docid":"12794099","text":"BACKGROUND There is overwhelming evidence that behavioural factors influence health, but their combined impact on the general population is less well documented. We aimed to quantify the potential combined impact of four health behaviours on mortality in men and women living in the general community. METHODS AND FINDINGS We examined the prospective relationship between lifestyle and mortality in a prospective population study of 20,244 men and women aged 45-79 y with no known cardiovascular disease or cancer at baseline survey in 1993-1997, living in the general community in the United Kingdom, and followed up to 2006. Participants scored one point for each health behaviour: current non-smoking, not physically inactive, moderate alcohol intake (1-14 units a week) and plasma vitamin C >50 mmol/l indicating fruit and vegetable intake of at least five servings a day, for a total score ranging from zero to four. After an average 11 y follow-up, the age-, sex-, body mass-, and social class-adjusted relative risks (95% confidence intervals) for all-cause mortality(1,987 deaths) for men and women who had three, two, one, and zero compared to four health behaviours were respectively, 1.39 (1.21-1.60), 1.95 (1.70--2.25), 2.52 (2.13-3.00), and 4.04 (2.95-5.54) p < 0.001 trend. The relationships were consistent in subgroups stratified by sex, age, body mass index, and social class, and after excluding deaths within 2 y. The trends were strongest for cardiovascular causes. The mortality risk for those with four compared to zero health behaviours was equivalent to being 14 y younger in chronological age. CONCLUSIONS Four health behaviours combined predict a 4-fold difference in total mortality in men and women, with an estimated impact equivalent to 14 y in chronological age.","title":"Combined Impact of Health Behaviours and Mortality in Men and Women: The EPIC-Norfolk Prospective Population Study"},{"docid":"27466734","text":"Objectives To develop and validate updated QRISK3 prediction algorithms to estimate the 10 year risk of cardiovascular disease in women and men accounting for potential new risk factors. Design Prospective open cohort study. Setting General practices in England providing data for the QResearch database. Participants 1309 QResearch general practices in England: 981 practices were used to develop the scores and a separate set of 328 practices were used to validate the scores. 7.89 million patients aged 25-84 years were in the derivation cohort and 2.67 million patients in the validation cohort. Patients were free of cardiovascular disease and not prescribed statins at baseline. Methods Cox proportional hazards models in the derivation cohort to derive separate risk equations in men and women for evaluation at 10 years. Risk factors considered included those already in QRISK2 (age, ethnicity, deprivation, systolic blood pressure, body mass index, total cholesterol: high density lipoprotein cholesterol ratio, smoking, family history of coronary heart disease in a first degree relative aged less than 60 years, type 1 diabetes, type 2 diabetes, treated hypertension, rheumatoid arthritis, atrial fibrillation, chronic kidney disease (stage 4 or 5)) and new risk factors (chronic kidney disease (stage 3, 4, or 5), a measure of systolic blood pressure variability (standard deviation of repeated measures), migraine, corticosteroids, systemic lupus erythematosus (SLE), atypical antipsychotics, severe mental illness, and HIV/AIDs). We also considered erectile dysfunction diagnosis or treatment in men. Measures of calibration and discrimination were determined in the validation cohort for men and women separately and for individual subgroups by age group, ethnicity, and baseline disease status. Main outcome measures Incident cardiovascular disease recorded on any of the following three linked data sources: general practice, mortality, or hospital admission records. Results 363 565 incident cases of cardiovascular disease were identified in the derivation cohort during follow-up arising from 50.8 million person years of observation. All new risk factors considered met the model inclusion criteria except for HIV/AIDS, which was not statistically significant. The models had good calibration and high levels of explained variation and discrimination. In women, the algorithm explained 59.6% of the variation in time to diagnosis of cardiovascular disease (R2, with higher values indicating more variation), and the D statistic was 2.48 and Harrell's C statistic was 0.88 (both measures of discrimination, with higher values indicating better discrimination). The corresponding values for men were 54.8%, 2.26, and 0.86. Overall performance of the updated QRISK3 algorithms was similar to the QRISK2 algorithms. Conclusion Updated QRISK3 risk prediction models were developed and validated. The inclusion of additional clinical variables in QRISK3 (chronic kidney disease, a measure of systolic blood pressure variability (standard deviation of repeated measures), migraine, corticosteroids, SLE, atypical antipsychotics, severe mental illness, and erectile dysfunction) can help enable doctors to identify those at most risk of heart disease and stroke.","title":"Development and validation of QRISK3 risk prediction algorithms to estimate future risk of cardiovascular disease: prospective cohort study"},{"docid":"12561083","text":"BACKGROUND Several studies have demonstrated that women with nonobstructive coronary disease have a high rate of subsequent investigations, rehospitalizations for recurrent chest pain, and repeat coronary angiography. The sex specificity of this finding is unclear. We therefore undertook an evaluation of sex differences in rehospitalization for acute coronary syndrome (ACS) or chest pain in patients with \"angiographically normal\" coronaries. METHODS A retrospective cohort study using prospectively collected angiographic and clinical data on all patients in British Columbia, Canada, presenting for their first cardiac catheterization with suspected ischemic heart disease but angiographically normal coronaries. RESULTS Among 32,856 patients, 7.1% of men versus 23.3% of women were angiographically normal (P < .001). Among angiographically normal patients, women were older and more likely to present with hypertension, prior stroke, chronic obstructive pulmonary disease, and peripheral vascular disease than men, but Canadian Cardiovascular Society class of angina did not vary by sex. Within 1 year, 1.0% died, (19 women, 18 men, P = .27) and 0.6% had a stroke (13 women, 9 men, P = .91). Readmission to hospital for ACS or chest pain requiring catheterization was significantly higher in women compared to men (adjusted OR 4.06; 95% CI 1.15-14.31). CONCLUSIONS In a contemporary, population-based cohort presenting for cardiac catheterization for suspected ischemia, women with angiographically normal coronaries were >4 times more likely to be readmitted to hospital for ACS/chest pain within 180 days compared to men. The observed sex difference has important social and economic implications and suggests that traditional diagnostic methods may not be optimal for women.","title":"Angina with \"normal\" coronary arteries: sex differences in outcomes."},{"docid":"11630388","text":"BACKGROUND Obesity is associated with diverse health risks, but the role of body weight as a risk factor for death remains controversial. METHODS We examined the association between body weight and the risk of death in a 12-year prospective cohort study of 1,213,829 Koreans between the ages of 30 and 95 years. We examined 82,372 deaths from any cause and 48,731 deaths from specific diseases (including 29,123 from cancer, 16,426 from atherosclerotic cardiovascular disease, and 3362 from respiratory disease) in relation to the body-mass index (BMI) (the weight in kilograms divided by the square of the height in meters). RESULTS In both sexes, the average baseline BMI was 23.2, and the rate of death from any cause had a J-shaped association with the BMI, regardless of cigarette-smoking history. The risk of death from any cause was lowest among patients with a BMI of 23.0 to 24.9. In all groups, the risk of death from respiratory causes was higher among subjects with a lower BMI, and the risk of death from atherosclerotic cardiovascular disease or cancer was higher among subjects with a higher BMI. The relative risk of death associated with BMI declined with increasing age. CONCLUSIONS Underweight, overweight, and obese men and women had higher rates of death than men and women of normal weight. The association of BMI with death varied according to the cause of death and was modified by age, sex, and smoking history.","title":"Body-mass index and mortality in Korean men and women."},{"docid":"15984735","text":"OBJECTIVE To evaluate the association between migraine and cardiovascular disease, including stroke, myocardial infarction, and death due to cardiovascular disease. DESIGN Systematic review and meta-analysis. DATA SOURCES Electronic databases (PubMed, Embase, Cochrane Library) and reference lists of included studies and reviews published until January 2009. Selection criteria Case-control and cohort studies investigating the association between any migraine or specific migraine subtypes and cardiovascular disease. Review methods Two investigators independently assessed eligibility of identified studies in a two step approach. Disagreements were resolved by consensus. Studies were grouped according to a priori categories on migraine and cardiovascular disease. DATA EXTRACTION Two investigators extracted data. Pooled relative risks and 95% confidence intervals were calculated. RESULTS Studies were heterogeneous for participant characteristics and definition of cardiovascular disease. Nine studies investigated the association between any migraine and ischaemic stroke (pooled relative risk 1.73, 95% confidence interval 1.31 to 2.29). Additional analyses indicated a significantly higher risk among people who had migraine with aura (2.16, 1.53 to 3.03) compared with people who had migraine without aura (1.23, 0.90 to 1.69; meta-regression for aura status P=0.02). Furthermore, results suggested a greater risk among women (2.08, 1.13 to 3.84) compared with men (1.37, 0.89 to 2.11). Age less than 45 years, smoking, and oral contraceptive use further increased the risk. Eight studies investigated the association between migraine and myocardial infarction (1.12, 0.95 to 1.32) and five between migraine and death due to cardiovascular disease (1.03, 0.79 to 1.34). Only one study investigated the association between women who had migraine with aura and myocardial infarction and death due to cardiovascular disease, showing a twofold increased risk. CONCLUSION Migraine is associated with a twofold increased risk of ischaemic stroke, which is only apparent among people who have migraine with aura. Our results also suggest a higher risk among women and risk was further magnified for people with migraine who were aged less than 45, smokers, and women who used oral contraceptives. We did not find an overall association between any migraine and myocardial infarction or death due to cardiovascular disease. Too few studies are available to reliably evaluate the impact of modifying factors, such as migraine aura, on these associations.","title":"Migraine and cardiovascular disease: systematic review and meta-analysis."},{"docid":"25355575","text":"Since the beginning of the 1990s the public health situation in Russia has been characterized by an extremely high mortality and a significant reduction in life expectancy. Cardiovascular diseases remained the major cause of death. Only a few large population studies were conducted in Russia during this period. A total of 1968 men and 1737 women aged 18–75 years participated in a health survey in Arkhangelsk, Russia, over the period 1999–2000. Investigation included assessment of classic cardiovascular risk factors (family history, smoking, blood pressure, and blood lipids) along with general health variables. The paper presents sex specific data on risk factors for coronary heart disease. Though the cardiovascular mortality is high in Russia, the calculated risk for coronary heart disease (the Framingham risk score and the Norwegian risk score) was lower in all age groups of men and women in Arkhangelsk compared with studies from the Western Europe and USA. Our data suggest that high cardiovascular mortality in Russia may be driven not only by the classic risk factors for coronary heart disease.","title":"High cardiovascular mortality in Russia cannot be explained by the classical risk factors. The Arkhangelsk study 2000"},{"docid":"752423","text":"BACKGROUND A reduction in compliance of the large-sized cardiothoracic (central) arteries is an independent risk factor for the development of cardiovascular disease with advancing age. METHODS AND RESULTS We determined the role of habitual exercise on the age-related decrease in central arterial compliance by using both cross-sectional and interventional approaches. First, we studied 151 healthy men aged 18 to 77 years: 54 were sedentary, 45 were recreationally active, and 53 were endurance exercise-trained. Central arterial compliance (simultaneous B-mode ultrasound and arterial applanation tonometry on the common carotid artery) was lower (P:<0.05) in middle-aged and older men than in young men in all 3 groups. There were no significant differences between sedentary and recreationally active men at any age. However, arterial compliance in the endurance-trained middle-aged and older men was 20% to 35% higher than in the 2 less active groups (P:<0.01). As such, age-related differences in central arterial compliance were smaller in the endurance-trained men than in the sedentary and recreationally active men. Second, we studied 20 middle-aged and older (53+/-2 years) sedentary healthy men before and after a 3-month aerobic exercise intervention (primarily walking). Regular exercise increased central arterial compliance (P:<0.01) to levels similar to those of the middle-aged and older endurance-trained men. These effects were independent of changes in body mass, adiposity, arterial blood pressure, or maximal oxygen consumption. CONCLUSIONS Regular aerobic-endurance exercise attenuates age-related reductions in central arterial compliance and restores levels in previously sedentary healthy middle-aged and older men. This may be one mechanism by which habitual exercise lowers the risk of cardiovascular disease in this population.","title":"Aging, habitual exercise, and dynamic arterial compliance."},{"docid":"75636923","text":"Metabolic syndrome is diagnosed when three or more of the following criteria are met: abdominal obesity (waist circumference more than 102 cm in men and 88 cm in women); hypertriglyceridemia of 150 mg/dl or above; a high-density lipoprotein (HDL) cholesterol level less than 40 mg/dl in men or 50 mg/dl in women; blood pressure of 130/85 mm Hg or higher; or fasting glucose of at least 110 mg/dl. Individuals with metabolic syndrome are likelier than others to develop diabetes and cardiovascular disease and have increased mortality from all causes (and from cardiovascular disease in particular). The investigators attempted to determine the prevalence of the syndrome in the United States by analyzing data on 8814 men and women 20 years of age or older who took part in the Third National Health and Nutrition Examination Survey in the years 1988 to 1994. This is a cross-sectional health survey of a sample of the noninstitutionalized civilian American population. The overall age-adjusted prevalence of metabolic syndrome was 23.7%. The prevalence rose from 6.7% in persons 20 to 29 years of age to 42% in those aged 70 years and more. There was virtually no gender-related difference in prevalence rates for the combined racial groups. Metabolic syndrome was most prevalent in Mexican Americans and least prevalent in whites, African Americans, and \"others. \" Among both African Americans and Mexican Americans, women had higher prevalence rates than men. Extrapolating from age-specific prevalence rates and US census counts from the year 2000, 47 million US residents have metabolic syndrome. Considering its prevalence, it seems important to estimate the direct medical costs of metabolic syndrome. In the great majority of cases the critical causes are improper nutrition and insufficient physical activity, emphasizing the importance of controlling obesity and encouraging physical activity in the United States.","title":"Prevalence of the Metabolic Syndrome Among Us Adults: Findings From the Third National Health and Nutrition Examination Survey"},{"docid":"3413083","text":"BACKGROUND Following widespread rollout of chlamydia testing to non-specialist and community settings in the UK, many individuals receive a chlamydia test without being offered comprehensive STI and HIV testing. We assess sexual behaviour among testers in different settings with a view to understanding their need for other STI diagnostic services. METHODS A probability sample survey of the British population undertaken 2010-2012 (the third National Survey of Sexual Attitudes and Lifestyles). We analysed weighted data on chlamydia testing (past year), including location of most recent test, and diagnoses (past 5 years) from individuals aged 16-44 years reporting at least one sexual partner in the past year (4992 women, 3406 men). RESULTS Of the 26.8% (95% CI 25.4% to 28.2%) of women and 16.7% (15.5% to 18.1%) of men reporting a chlamydia test in the past year, 28.4% of women and 41.2% of men had tested in genitourinary medicine (GUM), 41.1% and 20.7% of women and men respectively tested in general practice (GP) and the remainder tested in other non-GUM settings. Women tested outside GUM were more likely to be older, in a relationship and to live in rural areas. Individuals tested outside GUM reported fewer risk behaviours; nevertheless, 11.0% (8.6% to 14.1%) of women and 6.8% (3.9% to 11.6%) of men tested in GP and 13.2% (10.2% to 16.8%) and 9.6% (6.5% to 13.8%) of women and men tested in other non-GUM settings reported 'unsafe sex', defined as two or more partners and no condom use with any partner in the past year. Individuals treated for chlamydia outside GUM in the past 5 years were less likely to report an HIV test in that time frame (women: 54.5% (42.7% to 65.7%) vs 74.1% (65.9% to 80.9%) in GUM; men: 23.9% (12.7% to 40.5%) vs 65.8% (56.2% to 74.3%)). CONCLUSIONS Most chlamydia testing occurred in non-GUM settings, among populations reporting fewer risk behaviours. However, there is a need to provide pathways to comprehensive STI care to the sizeable minority at higher risk.","title":"Patterns of chlamydia testing in different settings and implications for wider STI diagnosis and care: a probability sample survey of the British population"},{"docid":"17124832","text":"CONTEXT Previous studies indicate that the population attributable risk (PAR) of bladder cancer for tobacco smoking is 50% to 65% in men and 20% to 30% in women and that current cigarette smoking triples bladder cancer risk relative to never smoking. During the last 30 years, incidence rates have remained stable in the United States in men (123.8 per 100,000 person-years to 142.2 per 100,000 person-years) and women (32.5 per 100,000 person-years to 33.2 per 100,000 person-years); however, changing smoking prevalence and cigarette composition warrant revisiting risk estimates for smoking and bladder cancer. OBJECTIVE To evaluate the association between tobacco smoking and bladder cancer. DESIGN, SETTING, AND PARTICIPANTS Men (n = 281,394) and women (n = 186,134) of the National Institutes of Health-AARP (NIH-AARP) Diet and Health Study cohort completed a lifestyle questionnaire and were followed up between October 25, 1995, and December 31, 2006. Previous prospective cohort studies of smoking and incident bladder cancer were identified by systematic review and relative risks were estimated from fixed-effects models with heterogeneity assessed by the I(2) statistic. MAIN OUTCOME MEASURES Hazard ratios (HRs), PARs, and number needed to harm (NNH). RESULTS During 4,518,941 person-years of follow-up, incident bladder cancer occurred in 3896 men (144.0 per 100,000 person-years) and 627 women (34.5 per 100,000 person-years). Former smokers (119.8 per 100,000 person-years; HR, 2.22; 95% confidence interval [CI], 2.03-2.44; NNH, 1250) and current smokers (177.3 per 100,000 person-years; HR, 4.06; 95% CI, 3.66-4.50; NNH, 727) had higher risks of bladder cancer than never smokers (39.8 per 100,000 person-years). In contrast, the summary risk estimate for current smoking in 7 previous studies (initiated between 1963 and 1987) was 2.94 (95% CI, 2.45-3.54; I(2) = 0.0%). The PAR for ever smoking in our study was 0.50 (95% CI, 0.45-0.54) in men and 0.52 (95% CI, 0.45-0.59) in women. CONCLUSION Compared with a pooled estimate of US data from cohorts initiated between 1963 and 1987, relative risks for smoking in the more recent NIH-AARP Diet and Health Study cohort were higher, with PARs for women comparable with those for men.","title":"Association between smoking and risk of bladder cancer among men and women."},{"docid":"1711571","text":"PURPOSE Patients with type 2 diabetes mellitus (T2DM) have an increased fracture risk despite having higher areal bone mineral density (aBMD). This study aimed to clarify the association between glycemic and insulin resistance status and bone microarchitecture, and whether pentosidine and bone turnover markers play any roles in the association. METHODS A total of 2012 community-dwelling men aged ≥65years completed baseline measurements of spine aBMD, fasting plasma glucose (FPG) and serum insulin, hemoglobin A1c (HbA1c), osteocalcin, type I procollagen N-terminal propeptide, type I collagen C-terminal crosslinking telopeptide, tartrate-resistant acid phosphatase isoenzyme 5b, pentosidine, height and weight and an interview regarding past disease history. Homeostasis model assessment-insulin resistance (HOMA-IR) was also calculated. T2DM was defined as physician-diagnosed middle age or elderly-onset diabetes mellitus, or according to biochemical test results. To evaluate bone microarchitecture, trabecular bone score (TBS) was calculated at the same vertebrae as those used for aBMD measurement. RESULTS After excluding participants who had a disease history and/or were taking medications affecting bone metabolism, 1683 men (age, 72.9±5.2years) were analyzed. Men with T2DM had significantly higher aBMD compared to those without T2DM. There was no significant difference in TBS. However, FPG, HbA1c and HOMA-IR levels were significantly inversely correlated with TBS after adjusting for age, BMI and aBMD. Multivariate linear regression analyses revealed that glycemic indices (FPG and HbA1c) were significantly associated with increased aBMD and decreased TBS, and that HOMA-IR was associated only with TBS. These associations did not change after further adjusting for bone turnover makers and pentosidine levels. CONCLUSIONS Hyperglycemia and elevated insulin-resistance were associated with low TBS independently of bone turnover and pentosidine levels.","title":"Hyperglycemia is associated with increased bone mineral density and decreased trabecular bone score in elderly Japanese men: The Fujiwara-kyo osteoporosis risk in men (FORMEN) study."},{"docid":"409280","text":"BACKGROUND Few data have evaluated physician adherence to cardiovascular disease (CVD) prevention guidelines according to physician specialty or patient characteristics, particularly gender. METHODS AND RESULTS An online study of 500 randomly selected physicians (300 primary care physicians, 100 obstetricians/gynecologists, and 100 cardiologists) used a standardized questionnaire to assess awareness of, adoption of, and barriers to national CVD prevention guidelines by specialty. An experimental case study design tested physician accuracy and determinants of CVD risk level assignment and application of guidelines among high-, intermediate-, or low-risk patients. Intermediate-risk women, as assessed by the Framingham risk score, were significantly more likely to be assigned to a lower-risk category by primary care physicians than men with identical risk profiles (P<0.0001), and trends were similar for obstetricians/gynecologists and cardiologists. Assignment of risk level significantly predicted recommendations for lifestyle and preventive pharmacotherapy. After adjustment for risk assignment, the impact of patient gender on preventive care was not significant except for less aspirin (P<0.01) and more weight management recommended (P<0.04) for intermediate-risk women. Physicians did not rate themselves as very effective in their ability to help patients prevent CVD. Fewer than 1 in 5 physicians knew that more women than men die each year from CVD. CONCLUSIONS Perception of risk was the primary factor associated with CVD preventive recommendations. Gender disparities in recommendations for preventive therapy were explained largely by the lower perceived risk despite similar calculated risk for women versus men. Educational interventions for physicians are needed to improve the quality of CVD preventive care and lower morbidity and mortality from CVD for men and women.","title":"National study of physician awareness and adherence to cardiovascular disease prevention guidelines."},{"docid":"5939172","text":"PURPOSE To analyze the relationship between an aspect of drinking pattern (i.e., drinking with or without meals) and risk of all-cause and specific-cause mortality. METHODS The Risk Factors and Life Expectancy Study, is a pooling of a series of epidemiological studies conducted in Italy. Eight-thousand six-hundred and forty-seven men and 6521 women, age 30-59 at baseline, and free of cardiovascular disease, were followed for mortality from all causes, cardiovascular and noncardiovascular, during an average follow-up of 7 years. RESULTS Drinkers of wine outside meals exhibited higher death rates from all causes, noncardiovascular diseases, and cancer, as compared to drinkers of wine with meals. This association was independent from the cardiovascular disease (CVD) risk factors measured at baseline and the amount of alcohol consumed and seemed to be stronger in women as compared to men. CONCLUSIONS The present results indicate that drinking patterns may have important health implications, and attention should be given to this aspect of alcohol use and its relationship to health outcomes. The relationship between alcohol consumption and disease has been the focus of intensive scientific investigation (1-9). Most studies to date, however, have limitations. A major drawback is that limited information has been collected regarding the complex issue of alcohol consumption. In many studies, ascertainment of alcohol consumption frequently focused only on quantity of alcohol consumed without considering the many different components of alcohol consumption, particularly drinking pattern (10-12). It has been hypothesized, and preliminary data support the notion, that drinking pattern could have important influences on determining the health effects of alcohol (13,14). The present study examines the relationship between one aspect of drinking pattern (drinking wine outside meals) and mortality in a large cohort of men and women.","title":"Drinking pattern and mortality: the Italian Risk Factor and Life Expectancy pooling project."},{"docid":"23785605","text":"BACKGROUND Migraine, particularly with aura, is a risk factor for early-onset ischemic stroke. The underlying mechanisms are unknown, but may in part be due to migraineurs having an increased risk profile for cardiovascular disease. In this study, the authors compare the cardiovascular risk profile of adult migraineurs to that of nonmigraineurs. METHODS Participants (n = 5,755, 48% men, age 20 to 65 years) are from the Genetic Epidemiology of Migraine (GEM) study, a population-based study in the Netherlands. A total of 620 current migraineurs were identified: 31% with aura (MA), 64% without aura (MO), and 5% unclassified. Controls were 5,135 individuals without lifetime migraine. Measured cardiovascular risk factors included blood pressure (BP), serum total and high-density lipoprotein cholesterol (TC, HDL), smoking, oral contraceptive use, and the Framingham risk score for myocardial infarction or coronary heart disease (CHD) death. RESULTS Compared to controls, migraineurs were more likely to smoke (OR = 1.43 [1.1 to 1.8]), less likely to consume alcohol (OR = 0.58 [0.5 to 0.7]), and more likely to report a parental history of early myocardial infarction. Migraineurs with aura were more likely to have an unfavorable cholesterol profile (TC > or = 240 mg/dL [OR = 1.43 (0.97 to 2.1)], TC:HDL ratio > 5.0 [OR = 1.64 (1.1 to 2.4)]), have elevated BP (systolic BP > 140 mm Hg or diastolic BP > 90 mm Hg [OR = 1.76 (1.04 to 3.0)]), and report a history of early onset CHD or stroke (OR = 3.96 [1.1 to 14.3]); female migraineurs with aura were more likely to be using oral contraceptives (OR = 2.06 [1.05 to 4.0]). The odds of having an elevated Framingham risk score for CHD were approximately doubled for the migraineurs with aura. CONCLUSIONS Migraineurs, particularly with aura, have a higher cardiovascular risk profile than individuals without migraine.","title":"Cardiovascular risk factors and migraine: the GEM population-based study."},{"docid":"43629704","text":"BACKGROUND Lowering the blood cholesterol level may reduce the risk of coronary heart disease. This double-blind study was designed to determine whether the administration of pravastatin to men with hypercholesterolemia and no history of myocardial infarction reduced the combined incidence of nonfatal myocardial infarction and death from coronary heart disease. METHODS We randomly assigned 6595 men, 45 to 64 years of age, with a mean (+/- SD) plasma cholesterol level of 272 +/- 23 mg per deciliter (7.0 +/- 0.6 mmol per liter) to receive pravastatin (40 mg each evening) or placebo. The average follow-up period was 4.9 years. Medical records, electrocardiographic recordings, and the national death registry were used to determine the clinical end points. RESULTS Pravastatin lowered plasma cholesterol levels by 20 percent and low-density-lipoprotein cholesterol levels by 26 percent, whereas there was no change with placebo. There were 248 definite coronary events (specified as nonfatal myocardial infarction or death from coronary heart disease) in the placebo group, and 174 in the pravastatin group (relative reduction in risk with pravastatin, 31 percent; 95 percent confidence interval, 17 to 43 percent; P < 0.001). There were similar reductions in the risk of definite nonfatal myocardial infarctions (31 percent reduction, P < 0.001), death from coronary heart disease (definite cases alone: 28 percent reduction, P = 0.13; definite plus suspected cases: 33 percent reduction, P = 0.042), and death from all cardiovascular causes (32 percent reduction, P = 0.033). There was no excess of deaths from noncardiovascular causes in the pravastatin group. We observed a 22 percent reduction in the risk of death from any cause in the pravastatin group (95 percent confidence interval, 0 to 40 percent; P = 0.051). CONCLUSIONS Treatment with pravastatin significantly reduced the incidence of myocardial infarction and death from cardiovascular causes without adversely affecting the risk of death from noncardiovascular causes in men with moderate hypercholesterolemia and no history of myocardial infarction.","title":"Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group."},{"docid":"18199839","text":"BACKGROUND Persistent inflammation has been proposed to contribute to various stages in the pathogenesis of cardiovascular disease. Interleukin-6 receptor (IL6R) signalling propagates downstream inflammation cascades. To assess whether this pathway is causally relevant to coronary heart disease, we studied a functional genetic variant known to affect IL6R signalling. METHODS In a collaborative meta-analysis, we studied Asp358Ala (rs2228145) in IL6R in relation to a panel of conventional risk factors and inflammation biomarkers in 125,222 participants. We also compared the frequency of Asp358Ala in 51,441 patients with coronary heart disease and in 136,226 controls. To gain insight into possible mechanisms, we assessed Asp358Ala in relation to localised gene expression and to postlipopolysaccharide stimulation of interleukin 6. FINDINGS The minor allele frequency of Asp358Ala was 39%. Asp358Ala was not associated with lipid concentrations, blood pressure, adiposity, dysglycaemia, or smoking (p value for association per minor allele ≥0·04 for each). By contrast, for every copy of 358Ala inherited, mean concentration of IL6R increased by 34·3% (95% CI 30·4-38·2) and of interleukin 6 by 14·6% (10·7-18·4), and mean concentration of C-reactive protein was reduced by 7·5% (5·9-9·1) and of fibrinogen by 1·0% (0·7-1·3). For every copy of 358Ala inherited, risk of coronary heart disease was reduced by 3·4% (1·8-5·0). Asp358Ala was not related to IL6R mRNA levels or interleukin-6 production in monocytes. INTERPRETATION Large-scale human genetic and biomarker data are consistent with a causal association between IL6R-related pathways and coronary heart disease. FUNDING British Heart Foundation; UK Medical Research Council; UK National Institute of Health Research, Cambridge Biomedical Research Centre; BUPA Foundation.","title":"Interleukin-6 receptor pathways in coronary heart disease: a collaborative meta-analysis of 82 studies"},{"docid":"2052720","text":"OBJECTIVE To investigate the association between gastric cancer and prior infection with Helicobacter pylori. DESIGN Case-control comparison of prevalence of IgG antibodies to H pylori in blood samples collected prospectively, before diagnosis of gastric cancer in the cases. Presence of H pylori antibody (greater than 10 micrograms IgG/ml) determined by enzyme linked immunosorbent assay (ELISA). SUBJECTS 29 men with a subsequent diagnosis of gastric cancer and 116 aged matched controls selected from over 22,000 middle aged men participating in two ongoing cohort studies (the British United Provident Association study and the Caerphilly collaborative heart disease study), who had provided blood samples during 1975-1982. RESULTS 20 of the 29 cases (69%) and 54 of the 116 controls (47%) were positive for H pylori specific antibody. The median specific IgG concentration was significantly higher in the cases than controls (90 micrograms/ml v 3.6 micrograms/ml, p less than 0.01). The estimated odds ratio for the risk of gastric cancer in those with a history of infection with H pylori was 2.77 (95% confidence interval 1.04 to 7.97, 2p = 0.039). CONCLUSIONS H pylori infection may be an important cause of gastric cancer; between 35% and 55% of all cases may be associated with such an infection.","title":"Association between infection with Helicobacter pylori and risk of gastric cancer: evidence from a prospective investigation."},{"docid":"15925931","text":"BACKGROUND Whole-body magnetic resonance angiography (WB-MRA) has shown its potential for the non-invasive assessment of nearly the entire arterial vasculature within one examination. Since the presence of extra-cardiac atherosclerosis is associated with an increased risk of coronary events, our goal was to establish the relationship between WB-MRA findings, including a systemic atherosclerosis score index, and the presence of significant coronary artery disease (CAD). METHODS WB-MRA was performed on a 1.5T scanner in 50 patients scheduled to undergo elective cardiac catheterization for suspected CAD. In each patient, 40 extra-cardiac vessel segments were evaluated and assigned scores according to their luminal narrowing. The atherosclerosis score index (ASI) was generated as the ratio of summed scores to analyzable segments. RESULTS ASI was higher in patients with significant (> 50% stenosis) CAD (n = 27) vs. patients without CAD (n = 22; 1.56 vs. 1.28, p = 0.004). ASI correlated with PROCAM (R = 0.57, p < 0.001) and Framingham (R = 0.36, p = 0.01) risk scores as estimates of the 10-year risk of coronary events. A ROC derived ASI of > 1.54 predicted significant CAD with a sensitivity of 59%, specificity of 86% and a positive predictive value of 84%. Logistic regression revealed ASI > 1.54 as the strongest independent predictor for CAD with a 11-fold increase in likelihood to suffer from significant coronary disease. On the contrary, while 15/27 (55%) of patients with CAD exhibited at least one extra-cardiac stenosis > 50%, only 3/22 (14%) of those patients without CAD did (p = 0.003). The likelihood for an extra-cardiac stenosis when CAD is present differed between vascular territories and ranged from 15% for a carotid stenosis to 44% for a stenosis in the lower extremities. CONCLUSION This study provides important new evidence for the close association of extra-cardiac and coronary atherosclerosis. The novel findings that a WB-MRA derived systemic atherosclerosis score index is not only associated with established cardiovascular risk scores but is also predictive of significant CAD suggest its potential prognostic implications and underline the importance to screen for coronary disease in patients with extra-cardiac manifestations of atherosclerosis.","title":"Prediction of coronary artery disease by a systemic atherosclerosis score index derived from whole-body MR angiography"},{"docid":"16252863","text":"The list of preventable and reversible risk factors for atherosclerotic cardiovascular disease continues to grow. Cigarette smoking, high blood pressure, physical inactivity, elevated cholesterol, underlying lipoprotein abnormalities, lipoprotein(a), diabetes, overweight, male gender, and age are well-established risk factors. During the 1990s, there have been many reports associating elevated plasma homocysteine levels with arteriosclerotic cardiovascular disease and consistent evidence that dietary and supplemental folic acid can reduce homocysteine levels.1 2 The article by Robinson and colleagues3 in this issue of Circulation presents further evidence of the importance of homocysteine and suggestive evidence that plasma folate and plasma pyrixodal-l-phosphate (vitamin B6) are protective factors. Their study is part of the European Concerted Action Project,4 which examined 750 patients younger than age 60 with diagnoses within the previous 12 months of coronary, cerebrovascular, or peripheral vascular disease and 800 healthy control subjects. The patient groups were young (47 years for cases and 44 years for control subjects) and heterogeneous, with nonfatal clinical events or symptoms of arteriosclerotic cardiovascular disease supported by ECG, angiographic, or Doppler evidence; the study involved 19 centers in nine European countries. Men in the highest quintile for fasting total homocysteine (tHcy), compared with the remainder of the population, had an estimated relative risk of 2.2 (95% confidence interval [CI], 1.6 to 2.9), with a striking dose-response relationship and a more-than-multiplicative interaction with cigarette smoking and high blood pressure on vascular disease risk4 ; the corresponding estimated relative risk for coronary heart disease was similar (2.0; 95% CI 1.6 to 2.8). (tHcy is the sum of homocysteine and homocysteinyl moieties of oxidized disulfides, homocystine, and cysteine- homocysteine. ) Robinson and colleagues3 examined three B vitamins in detail to determine their effects on fasting and post–methionine-loading tHcy levels and any independent effects on cardiovascular disease …","title":"Preventing coronary heart disease: B vitamins and homocysteine."},{"docid":"44624045","text":"BACKGROUND Few previous prospective studies have examined differences in incident ischemic heart disease (IHD) risk between vegetarians and nonvegetarians. OBJECTIVE The objective was to examine the association of a vegetarian diet with risk of incident (nonfatal and fatal) IHD. DESIGN A total of 44,561 men and women living in England and Scotland who were enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Oxford study, of whom 34% consumed a vegetarian diet at baseline, were part of the analysis. Incident cases of IHD were identified through linkage with hospital records and death certificates. Serum lipids and blood pressure measurements were available for 1519 non cases, who were matched to IHD cases by sex and age. IHD risk by vegetarian status was estimated by using multivariate Cox proportional hazards models. RESULTS After an average follow-up of 11.6 y, there were 1235 IHD cases (1066 hospital admissions and 169 deaths). Compared with nonvegetarians, vegetarians had a lower mean BMI [in kg/m(2); -1.2 (95% CI: -1.3, -1.1)], non-HDL-cholesterol concentration [-0.45 (95% CI: -0.60, -0.30) mmol/L], and systolic blood pressure [-3.3 (95% CI: -5.9, -0.7) mm Hg]. Vegetarians had a 32% lower risk (HR: 0.68; 95% CI: 0.58, 0.81) of IHD than did nonvegetarians, which was only slightly attenuated after adjustment for BMI and did not differ materially by sex, age, BMI, smoking, or the presence of IHD risk factors. CONCLUSION Consuming a vegetarian diet was associated with lower IHD risk, a finding that is probably mediated by differences in non-HDL cholesterol, and systolic blood pressure.","title":"Risk of hospitalization or death from ischemic heart disease among British vegetarians and nonvegetarians: results from the EPIC-Oxford cohort study."},{"docid":"45027320","text":"BACKGROUND The aim of this study was to examine the clustering of four major lifestyle risk factors (smoking, heavy drinking, lack of fruit and vegetables consumption, and lack of physical activity), and to examine the variation across different socio-demographic groups in the English adult population. METHODS The study population was derived from the 2003 Health Survey for England (n=11,492). Clustering was examined by comparing the observed and expected prevalence of the different possible combinations. A multinomial multilevel regression model was conducted to examine the socio-demographic variation in the clustering of the four risk factors. RESULTS The study found that, when using British health recommendations, a majority of the English population have multiple lifestyle risk factors at the same time. Clustering was found at both ends of the lifestyle spectrum and was more pronounced for women than for men. Overall, multiple risk factors were more prevalent among men, lower social class households, singles, and people who are economically inactive, but less prevalent among home owners and older age groups. CONCLUSIONS The clustering of multiple risk factors provides support for multiple-behavior interventions as opposed to single-behavior interventions.","title":"The prevalence and clustering of four major lifestyle risk factors in an English adult population."},{"docid":"6327940","text":"Amino acids modulate the secretion of both insulin and glucagon; the composition of dietary protein therefore has the potential to influence the balance of glucagon and insulin activity. Soy protein, as well as many other vegan proteins, are higher in non-essential amino acids than most animal-derived food proteins, and as a result should preferentially favor glucagon production. Acting on hepatocytes, glucagon promotes (and insulin inhibits) cAMP-dependent mechanisms that down-regulate lipogenic enzymes and cholesterol synthesis, while up-regulating hepatic LDL receptors and production of the IGF-I antagonist IGFBP-1. The insulin-sensitizing properties of many vegan diets--high in fiber, low in saturated fat--should amplify these effects by down-regulating insulin secretion. Additionally, the relatively low essential amino acid content of some vegan diets may decrease hepatic IGF-I synthesis. Thus, diets featuring vegan proteins can be expected to lower elevated serum lipid levels, promote weight loss, and decrease circulating IGF-I activity. The latter effect should impede cancer induction (as is seen in animal studies with soy protein), lessen neutrophil-mediated inflammatory damage, and slow growth and maturation in children. In fact, vegans tend to have low serum lipids, lean physiques, shorter stature, later puberty, and decreased risk for certain prominent 'Western' cancers; a vegan diet has documented clinical efficacy in rheumatoid arthritis. Low-fat vegan diets may be especially protective in regard to cancers linked to insulin resistance--namely, breast and colon cancer--as well as prostate cancer; conversely, the high IGF-I activity associated with heavy ingestion of animal products may be largely responsible for the epidemic of 'Western' cancers in wealthy societies. Increased phytochemical intake is also likely to contribute to the reduction of cancer risk in vegans. Regression of coronary stenoses has been documented during low-fat vegan diets coupled with exercise training; such regimens also tend to markedly improve diabetic control and lower elevated blood pressure. Risk of many other degenerative disorders may be decreased in vegans, although reduced growth factor activity may be responsible for an increased risk of hemorrhagic stroke. By altering the glucagon/insulin balance, it is conceivable that supplemental intakes of key non-essential amino acids could enable omnivores to enjoy some of the health advantages of a vegan diet. An unnecessarily high intake of essential amino acids--either in the absolute sense or relative to total dietary protein--may prove to be as grave a risk factor for 'Western' degenerative diseases as is excessive fat intake.","title":"Vegan proteins may reduce risk of cancer, obesity, and cardiovascular disease by promoting increased glucagon activity."},{"docid":"5884524","text":"BACKGROUND Although unstable coronary artery disease is the most common reason for admission to a coronary care unit, the long-term prognosis of patients with this diagnosis is unknown. This is particularly true for patients with diabetes mellitus, who are known to have a high morbidity and mortality after an acute myocardial infarction. METHODS AND RESULTS Prospectively collected data from 6 different countries in the Organization to Assess Strategies for Ischemic Syndromes (OASIS) registry were analyzed to determine the 2-year prognosis of diabetic and nondiabetic patients who were hospitalized with unstable angina or non-Q-wave myocardial infarction. Overall, 1718 of 8013 registry patients (21%) had diabetes. Diabetic patients had a higher rate of coronary bypass surgery than nondiabetic patients (23% versus 20%, P:<0.001) but had similar rates of catheterization and angioplasty. Diabetes independently predicted mortality (relative risk [RR], 1.57; 95% CI, 1.38 to 1.81; P:<0.001), as well as cardiovascular death, new myocardial infarction, stroke, and new congestive heart failure. Moreover, compared with their nondiabetic counterparts, women had a significantly higher risk than men (RR, 1.98; 95% CI, 1.60 to 2.44; and RR, 1.28; 95% CI, 1.06 to 1.56, respectively). Interestingly, diabetic patients without prior cardiovascular disease had the same event rates for all outcomes as nondiabetic patients with previous vascular disease. CONCLUSIONS Hospitalization for unstable angina or non-Q-wave myocardial infarction predicts a high 2-year morbidity and mortality; this is especially evident for patients with diabetes. Diabetic patients with no previous cardiovascular disease have the same long-term morbidity and mortality as nondiabetic patients with established cardiovascular disease after hospitalization for unstable coronary artery disease.","title":"Impact of diabetes on long-term prognosis in patients with unstable angina and non-Q-wave myocardial infarction: results of the OASIS (Organization to Assess Strategies for Ischemic Syndromes) Registry."},{"docid":"9617381","text":"OBJECTIVE To evaluate long-term prognostic effect of serum noncholesterol sterols, including plant sterols, in middle-aged men with high cardiovascular disease (CVD) risk, without statins at baseline. METHODS This was a prospective study of 232 men (mean age 60 years) at high risk of CVD in 1985-1986. Most were hypercholesterolemic, 29 (12%) had a history of CVD or cancer, 6 (3%) had diabetes, and 46 (20%) had metabolic syndrome (MS). Measured noncholesterol sterols (expressed as absolute concentrations or ratios to serum cholesterol to standardize for cholesterol concentrations) included lathosterol and desmosterol (reflect cholesterol synthesis), and plant sterols (campesterol and sitosterol) and cholestanol (reflect cholesterol absorption). Main outcome measure was total mortality. RESULTS At baseline, markers of cholesterol synthesis and absorption showed expected inverse associations. During the 22-year follow-up 101 men (43%) died. At baseline, nonsurvivors smoked more, exercised less and had more components of MS (although not filling strict criteria), whereas traditional risk factors of CVD were not significantly different. Of the noncholesterol sterols (either absolute or ratio), only sitosterol was significantly higher in survivors than in nonsurvivors (P=0.02). In multivariable analyses, highest sitosterol-to-cholesterol tertile was associated with significantly lower mortality risk (HR 0.51, 95% CI 0.30-0.87) as compared to lowest tertile. Other associations were nonsignificant, although a \"global\" index of cholesterol metabolism (desmosterol-to-sitosterol ratio) suggested higher cholesterol synthesis and lower absorption to be associated with higher total and CVD mortality. CONCLUSION Higher serum plant sterol levels in middle-aged men predicted lower long-term mortality risk, possibly reflecting an association between higher synthesis/lower absorption of cholesterol and mortality.","title":"Serum plant and other noncholesterol sterols, cholesterol metabolism and 22-year mortality among middle-aged men."}],"string":"[\n {\n \"docid\": \"29253460\",\n \"text\": \"OBJECTIVE To assess whether sex differences exist in the angiographic severity, management and outcomes of acute coronary syndromes (ACS). METHODS The study comprised 7638 women and 19 117 men with ACS who underwent coronary angiography and were included in GRACE (Global Registry of Acute Coronary Events) from 1999-2006. Normal vessels/mild disease was defined as <50% stenosis in all epicardial vessels; advanced disease was defined as >or=one vessel with >or=50% stenosis. RESULTS Women were older than men and had higher rates of cardiovascular risk factors. Men and women presented equally with chest pain; however, jaw pain and nausea were more frequent among women. Women were more likely to have normal/mild disease (12% vs 6%, p<0.001) and less likely to have left-main and three-vessel disease (27% vs 32%, p<0.001) or undergo percutaneous coronary intervention (65% vs 68%, p<0.001). Women and men with normal and mild disease were treated less aggressively than those with advanced disease. Women with advanced disease had a higher risk of death (4% vs 3%, p<0.01). After adjustment for age and extent of disease, women were more likely to have adverse outcomes (death, myocardial infarction, stroke and rehospitalisation) at six months compared to men (odds ratio 1.24, 95% confidence interval 1.14 to 1.34); however, sex differences in mortality were no longer statistically significant. CONCLUSIONS Women with ACS were more likely to have cardiovascular disease risk factors and atypical symptoms such as nausea compared with men, but were more likely to have normal/mild angiographic coronary artery disease. Further study regarding sex differences related to disease severity is warranted.\",\n \"title\": \"Sex-related differences in the presentation, treatment and outcomes among patients with acute coronary syndromes: the Global Registry of Acute Coronary Events.\"\n },\n {\n \"docid\": \"5698494\",\n \"text\": \"OBJECTIVES To investigate whether statins reduce all cause mortality and major coronary and cerebrovascular events in people without established cardiovascular disease but with cardiovascular risk factors, and whether these effects are similar in men and women, in young and older (>65 years) people, and in people with diabetes mellitus. DESIGN Meta-analysis of randomised trials. DATA SOURCES Cochrane controlled trials register, Embase, and Medline. Data abstraction Two independent investigators identified studies on the clinical effects of statins compared with a placebo or control group and with follow-up of at least one year, at least 80% or more participants without established cardiovascular disease, and outcome data on mortality and major cardiovascular disease events. Heterogeneity was assessed using the Q and I(2) statistics. Publication bias was assessed by visual examination of funnel plots and the Egger regression test. RESULTS 10 trials enrolled a total of 70 388 people, of whom 23 681 (34%) were women and 16 078 (23%) had diabetes mellitus. Mean follow-up was 4.1 years. Treatment with statins significantly reduced the risk of all cause mortality (odds ratio 0.88, 95% confidence interval 0.81 to 0.96), major coronary events (0.70, 0.61 to 0.81), and major cerebrovascular events (0.81, 0.71 to 0.93). No evidence of an increased risk of cancer was observed. There was no significant heterogeneity of the treatment effect in clinical subgroups. CONCLUSION In patients without established cardiovascular disease but with cardiovascular risk factors, statin use was associated with significantly improved survival and large reductions in the risk of major cardiovascular events.\",\n \"title\": \"The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials\"\n },\n {\n \"docid\": \"12770738\",\n \"text\": \"BACKGROUND Questions remain as to whether higher levels of cardiorespiratory fitness, a measure of regular physical activity, are associated with lower risk of cardiovascular disease (CVD) mortality in overweight and obese individuals with diabetes. Our objective was to quantify the independent and joint relations of cardiorespiratory fitness (hereafter, fitness) and body mass index (BMI; calculated as weight in kilograms divided by the square of height in meters) with CVD mortality in men with diabetes. METHODS This study was conducted using prospective observational data from the Aerobics Center Longitudinal Study. Study participants comprised 2316 men with no history of stroke or myocardial infarction and who were diagnosed as having diabetes (mean [SD] age, 50 [10] years); had a medical examination, including a maximal exercise test during 1970 to 1997 with mortality surveillance to December 31, 1998; and had a BMI of 18.5 or greater and less than 35.0. The main outcome measure was CVD mortality across levels of fitness with stratification by BMI. RESULTS We identified 179 CVD deaths during a mean (SD) follow-up of 15.9 (7.9) years and 36,710 man-years of exposure. In a model containing age, examination year, fasting glucose level, systolic blood pressure, parental history of premature CVD, total cholesterol level, cigarette smoking, abnormal resting, and exercise electrocardiograms, a significantly higher adjusted risk of mortality was observed in men with a low fitness level who were normal weight (hazard ratio, 2.7 [95% confidence interval, 1.3-5.7]), overweight (hazard ratio, 2.7 [95% confidence interval, 1.4-5.1]), and class 1 obese (hazard ratio, 2.8 [95% confidence interval, 1.4-5.1]) compared with normal weight men with a high fitness level. CONCLUSION In this cohort of men with diabetes, low fitness level was associated with increased risk of CVD mortality within normal weight, overweight, and class 1 obese weight categories.\",\n \"title\": \"Cardiorespiratory fitness and body mass index as predictors of cardiovascular disease mortality among men with diabetes.\"\n },\n {\n \"docid\": \"8780599\",\n \"text\": \"OBJECTIVE Although the Polypill concept (proposed in 2003) is promising in terms of benefits for cardiovascular risk management, the potential costs and adverse effects are its main pitfalls. The objective of this study was to identify a tastier and safer alternative to the Polypill: the Polymeal. METHODS Data on the ingredients of the Polymeal were taken from the literature. The evidence based recipe included wine, fish, dark chocolate, fruits, vegetables, garlic, and almonds. Data from the Framingham heart study and the Framingham offspring study were used to build life tables to model the benefits of the Polymeal in the general population from age 50, assuming multiplicative correlations. RESULTS Combining the ingredients of the Polymeal would reduce cardiovascular disease events by 76%. For men, taking the Polymeal daily represented an increase in total life expectancy of 6.6 years, an increase in life expectancy free from cardiovascular disease of 9.0 years, and a decrease in life expectancy with cardiovascular disease of 2.4 years. The corresponding differences for women were 4.8, 8.1, and 3.3 years. CONCLUSION The Polymeal promises to be an effective, non-pharmacological, safe, cheap, and tasty alternative to reduce cardiovascular morbidity and increase life expectancy in the general population.\",\n \"title\": \"The Polymeal: a more natural, safer, and probably tastier (than the Polypill) strategy to reduce cardiovascular disease by more than 75%.\"\n },\n {\n \"docid\": \"21003930\",\n \"text\": \"BACKGROUND Long-term exposure to pollution can lead to an increase in the rate of decline of lung function, especially in older individuals and in those with chronic obstructive pulmonary disease (COPD), whereas shorter-term exposure at higher pollution levels has been implicated in causing excess deaths from ischaemic heart disease and exacerbations of COPD. We aimed to assess the effects on respiratory and cardiovascular responses of walking down a busy street with high levels of pollution compared with walking in a traffic-free area with lower pollution levels in older adults. METHODS In this randomised, crossover study, we recruited men and women aged 60 years and older with angiographically proven stable ischaemic heart disease or stage 2 Global initiative for Obstructive Lung Disease (GOLD) COPD who had been clinically stable for 6 months, and age-matched healthy volunteers. Individuals with ischaemic heart disease or COPD were recruited from existing databases or outpatient respiratory and cardiology clinics at the Royal Brompton & Harefield NHS Foundation Trust and age-matched healthy volunteers using advertising and existing databases. All participants had abstained from smoking for at least 12 months and medications were taken as recommended by participants' doctors during the study. Participants were randomly assigned by drawing numbered disks at random from a bag to do a 2 h walk either along a commercial street in London (Oxford Street) or in an urban park (Hyde Park). Baseline measurements of participants were taken before the walk in the hospital laboratory. During each walk session, black carbon, particulate matter (PM) concentrations, ultrafine particles, and nitrogen dioxide (NO2) concentrations were measured. FINDINGS Between October, 2012, and June, 2014, we screened 135 participants, of whom 40 healthy volunteers, 40 individuals with COPD, and 39 with ischaemic heart disease were recruited. Concentrations of black carbon, NO2, PM10, PM2.5, and ultrafine particles were higher on Oxford Street than in Hyde Park. Participants with COPD reported more cough (odds ratio [OR] 1·95, 95% CI 0·96-3·95; p<0·1), sputum (3·15, 1·39-7·13; p<0·05), shortness of breath (1·86, 0·97-3·57; p<0·1), and wheeze (4·00, 1·52-10·50; p<0·05) after walking down Oxford Street compared with Hyde Park. In all participants, irrespective of their disease status, walking in Hyde Park led to an increase in lung function (forced expiratory volume in the first second [FEV1] and forced vital capacity [FVC]) and a decrease in pulse wave velocity (PWV) and augmentation index up to 26 h after the walk. By contrast, these beneficial responses were attenuated after walking on Oxford Street. In participants with COPD, a reduction in FEV1 and FVC, and an increase in R5-20 were associated with an increase in during-walk exposure to NO2, ultrafine particles and PM2.5, and an increase in PWV and augmentation index with NO2 and ultrafine particles. In healthy volunteers, PWV and augmentation index were associated both with black carbon and ultrafine particles. INTERPRETATION Short-term exposure to traffic pollution prevents the beneficial cardiopulmonary effects of walking in people with COPD, ischaemic heart disease, and those free from chronic cardiopulmonary diseases. Medication use might reduce the adverse effects of air pollution in individuals with ischaemic heart disease. Policies should aim to control ambient levels of air pollution along busy streets in view of these negative health effects. FUNDING British Heart Foundation.\",\n \"title\": \"Respiratory and cardiovascular responses to walking down a traffic-polluted road compared with walking in a traffic-free area in participants aged 60 years and older with chronic lung or heart disease and age-matched healthy controls: a randomised, crossover study\"\n },\n {\n \"docid\": \"39368721\",\n \"text\": \"OBJECTIVE to investigate the role of glucose tolerance in the development of hypertension. DESIGN Retrospective analysis of the results of a health check up in a group of clinically healthy middle aged men in the late 1960s (median year 1968). The subjects were invited to enter into a primary prevention trial for cardiovascular disease in 1974, when they underwent clinical examination for risk factors. The trial was completed in 1979, when the men were re-examined. Follow up was in 1986. SETTING Institute of Occupational Health, Helsinki, Finland and second department of medicine, University of Helsinki. SUBJECTS In all, 3490 men born during 1919-34 participated in a health check up in the late 1960s. In 1974, 1815 of these men who were clinically healthy were entered into a primary prevention trial for cardiovascular disease. On clinical examination 1222 of the men were considered at high risk of cardiovascular disease. Of these, 612 received an intervention and were excluded from the study. A total of 593 men were without risk factors. The study comprised all of the men who did not have an intervention (n = 1203). In 1979, 1120 men were re-examined, and in 1986 945 men attended follow up. There were two groups for analysis: one comprising all subjects and the other comprising only men who were normotensive in 1968 and for whom complete information was available. INTERVENTIONS By 1979, 103 men were taking antihypertensive drugs, and by 1986, 131 were taking antihypertensive drugs and 12 were taking drugs for hyperglycaemia. MAIN OUTCOME MEASURES Blood glucose concentration one hour after a glucose load, blood pressure, and body weight were measured in 1968, 1974, and 1979. In 1986 blood pressure and body weight were recorded. RESULTS Men who were hypertensive in 1986 had significantly higher blood pressures (p less than 0.0001) and (after adjustment for body mass index and alcohol intake) significantly higher blood glucose concentrations one hour after a glucose load at all examinations than those who were normotensive in 1986. Regression analysis showed that the higher the blood glucose concentration after a glucose load in 1968 the higher the blood pressure during the following years. Those men between the second and third tertiles of blood glucose concentration in 1968 had a significantly higher risk of developing hypertension (odds ratio 1.71, 95% confidence interval 1.05 to 2.77) compared with those below the first tertile. CONCLUSION In this study men who developed hypertension tended to have shown an increased intolerance to glucose up to 18 years before the clinical manifestation of their disorder. Blood glucose concentration one hour after a glucose load was an independent predictor of future hypertension.\",\n \"title\": \"Glucose tolerance and blood pressure: long term follow up in middle aged men.\"\n },\n {\n \"docid\": \"12794099\",\n \"text\": \"BACKGROUND There is overwhelming evidence that behavioural factors influence health, but their combined impact on the general population is less well documented. We aimed to quantify the potential combined impact of four health behaviours on mortality in men and women living in the general community. METHODS AND FINDINGS We examined the prospective relationship between lifestyle and mortality in a prospective population study of 20,244 men and women aged 45-79 y with no known cardiovascular disease or cancer at baseline survey in 1993-1997, living in the general community in the United Kingdom, and followed up to 2006. Participants scored one point for each health behaviour: current non-smoking, not physically inactive, moderate alcohol intake (1-14 units a week) and plasma vitamin C >50 mmol/l indicating fruit and vegetable intake of at least five servings a day, for a total score ranging from zero to four. After an average 11 y follow-up, the age-, sex-, body mass-, and social class-adjusted relative risks (95% confidence intervals) for all-cause mortality(1,987 deaths) for men and women who had three, two, one, and zero compared to four health behaviours were respectively, 1.39 (1.21-1.60), 1.95 (1.70--2.25), 2.52 (2.13-3.00), and 4.04 (2.95-5.54) p < 0.001 trend. The relationships were consistent in subgroups stratified by sex, age, body mass index, and social class, and after excluding deaths within 2 y. The trends were strongest for cardiovascular causes. The mortality risk for those with four compared to zero health behaviours was equivalent to being 14 y younger in chronological age. CONCLUSIONS Four health behaviours combined predict a 4-fold difference in total mortality in men and women, with an estimated impact equivalent to 14 y in chronological age.\",\n \"title\": \"Combined Impact of Health Behaviours and Mortality in Men and Women: The EPIC-Norfolk Prospective Population Study\"\n },\n {\n \"docid\": \"27466734\",\n \"text\": \"Objectives To develop and validate updated QRISK3 prediction algorithms to estimate the 10 year risk of cardiovascular disease in women and men accounting for potential new risk factors. Design Prospective open cohort study. Setting General practices in England providing data for the QResearch database. Participants 1309 QResearch general practices in England: 981 practices were used to develop the scores and a separate set of 328 practices were used to validate the scores. 7.89 million patients aged 25-84 years were in the derivation cohort and 2.67 million patients in the validation cohort. Patients were free of cardiovascular disease and not prescribed statins at baseline. Methods Cox proportional hazards models in the derivation cohort to derive separate risk equations in men and women for evaluation at 10 years. Risk factors considered included those already in QRISK2 (age, ethnicity, deprivation, systolic blood pressure, body mass index, total cholesterol: high density lipoprotein cholesterol ratio, smoking, family history of coronary heart disease in a first degree relative aged less than 60 years, type 1 diabetes, type 2 diabetes, treated hypertension, rheumatoid arthritis, atrial fibrillation, chronic kidney disease (stage 4 or 5)) and new risk factors (chronic kidney disease (stage 3, 4, or 5), a measure of systolic blood pressure variability (standard deviation of repeated measures), migraine, corticosteroids, systemic lupus erythematosus (SLE), atypical antipsychotics, severe mental illness, and HIV/AIDs). We also considered erectile dysfunction diagnosis or treatment in men. Measures of calibration and discrimination were determined in the validation cohort for men and women separately and for individual subgroups by age group, ethnicity, and baseline disease status. Main outcome measures Incident cardiovascular disease recorded on any of the following three linked data sources: general practice, mortality, or hospital admission records. Results 363 565 incident cases of cardiovascular disease were identified in the derivation cohort during follow-up arising from 50.8 million person years of observation. All new risk factors considered met the model inclusion criteria except for HIV/AIDS, which was not statistically significant. The models had good calibration and high levels of explained variation and discrimination. In women, the algorithm explained 59.6% of the variation in time to diagnosis of cardiovascular disease (R2, with higher values indicating more variation), and the D statistic was 2.48 and Harrell's C statistic was 0.88 (both measures of discrimination, with higher values indicating better discrimination). The corresponding values for men were 54.8%, 2.26, and 0.86. Overall performance of the updated QRISK3 algorithms was similar to the QRISK2 algorithms. Conclusion Updated QRISK3 risk prediction models were developed and validated. The inclusion of additional clinical variables in QRISK3 (chronic kidney disease, a measure of systolic blood pressure variability (standard deviation of repeated measures), migraine, corticosteroids, SLE, atypical antipsychotics, severe mental illness, and erectile dysfunction) can help enable doctors to identify those at most risk of heart disease and stroke.\",\n \"title\": \"Development and validation of QRISK3 risk prediction algorithms to estimate future risk of cardiovascular disease: prospective cohort study\"\n },\n {\n \"docid\": \"12561083\",\n \"text\": \"BACKGROUND Several studies have demonstrated that women with nonobstructive coronary disease have a high rate of subsequent investigations, rehospitalizations for recurrent chest pain, and repeat coronary angiography. The sex specificity of this finding is unclear. We therefore undertook an evaluation of sex differences in rehospitalization for acute coronary syndrome (ACS) or chest pain in patients with \\\"angiographically normal\\\" coronaries. METHODS A retrospective cohort study using prospectively collected angiographic and clinical data on all patients in British Columbia, Canada, presenting for their first cardiac catheterization with suspected ischemic heart disease but angiographically normal coronaries. RESULTS Among 32,856 patients, 7.1% of men versus 23.3% of women were angiographically normal (P < .001). Among angiographically normal patients, women were older and more likely to present with hypertension, prior stroke, chronic obstructive pulmonary disease, and peripheral vascular disease than men, but Canadian Cardiovascular Society class of angina did not vary by sex. Within 1 year, 1.0% died, (19 women, 18 men, P = .27) and 0.6% had a stroke (13 women, 9 men, P = .91). Readmission to hospital for ACS or chest pain requiring catheterization was significantly higher in women compared to men (adjusted OR 4.06; 95% CI 1.15-14.31). CONCLUSIONS In a contemporary, population-based cohort presenting for cardiac catheterization for suspected ischemia, women with angiographically normal coronaries were >4 times more likely to be readmitted to hospital for ACS/chest pain within 180 days compared to men. The observed sex difference has important social and economic implications and suggests that traditional diagnostic methods may not be optimal for women.\",\n \"title\": \"Angina with \\\"normal\\\" coronary arteries: sex differences in outcomes.\"\n },\n {\n \"docid\": \"11630388\",\n \"text\": \"BACKGROUND Obesity is associated with diverse health risks, but the role of body weight as a risk factor for death remains controversial. METHODS We examined the association between body weight and the risk of death in a 12-year prospective cohort study of 1,213,829 Koreans between the ages of 30 and 95 years. We examined 82,372 deaths from any cause and 48,731 deaths from specific diseases (including 29,123 from cancer, 16,426 from atherosclerotic cardiovascular disease, and 3362 from respiratory disease) in relation to the body-mass index (BMI) (the weight in kilograms divided by the square of the height in meters). RESULTS In both sexes, the average baseline BMI was 23.2, and the rate of death from any cause had a J-shaped association with the BMI, regardless of cigarette-smoking history. The risk of death from any cause was lowest among patients with a BMI of 23.0 to 24.9. In all groups, the risk of death from respiratory causes was higher among subjects with a lower BMI, and the risk of death from atherosclerotic cardiovascular disease or cancer was higher among subjects with a higher BMI. The relative risk of death associated with BMI declined with increasing age. CONCLUSIONS Underweight, overweight, and obese men and women had higher rates of death than men and women of normal weight. The association of BMI with death varied according to the cause of death and was modified by age, sex, and smoking history.\",\n \"title\": \"Body-mass index and mortality in Korean men and women.\"\n },\n {\n \"docid\": \"15984735\",\n \"text\": \"OBJECTIVE To evaluate the association between migraine and cardiovascular disease, including stroke, myocardial infarction, and death due to cardiovascular disease. DESIGN Systematic review and meta-analysis. DATA SOURCES Electronic databases (PubMed, Embase, Cochrane Library) and reference lists of included studies and reviews published until January 2009. Selection criteria Case-control and cohort studies investigating the association between any migraine or specific migraine subtypes and cardiovascular disease. Review methods Two investigators independently assessed eligibility of identified studies in a two step approach. Disagreements were resolved by consensus. Studies were grouped according to a priori categories on migraine and cardiovascular disease. DATA EXTRACTION Two investigators extracted data. Pooled relative risks and 95% confidence intervals were calculated. RESULTS Studies were heterogeneous for participant characteristics and definition of cardiovascular disease. Nine studies investigated the association between any migraine and ischaemic stroke (pooled relative risk 1.73, 95% confidence interval 1.31 to 2.29). Additional analyses indicated a significantly higher risk among people who had migraine with aura (2.16, 1.53 to 3.03) compared with people who had migraine without aura (1.23, 0.90 to 1.69; meta-regression for aura status P=0.02). Furthermore, results suggested a greater risk among women (2.08, 1.13 to 3.84) compared with men (1.37, 0.89 to 2.11). Age less than 45 years, smoking, and oral contraceptive use further increased the risk. Eight studies investigated the association between migraine and myocardial infarction (1.12, 0.95 to 1.32) and five between migraine and death due to cardiovascular disease (1.03, 0.79 to 1.34). Only one study investigated the association between women who had migraine with aura and myocardial infarction and death due to cardiovascular disease, showing a twofold increased risk. CONCLUSION Migraine is associated with a twofold increased risk of ischaemic stroke, which is only apparent among people who have migraine with aura. Our results also suggest a higher risk among women and risk was further magnified for people with migraine who were aged less than 45, smokers, and women who used oral contraceptives. We did not find an overall association between any migraine and myocardial infarction or death due to cardiovascular disease. Too few studies are available to reliably evaluate the impact of modifying factors, such as migraine aura, on these associations.\",\n \"title\": \"Migraine and cardiovascular disease: systematic review and meta-analysis.\"\n },\n {\n \"docid\": \"25355575\",\n \"text\": \"Since the beginning of the 1990s the public health situation in Russia has been characterized by an extremely high mortality and a significant reduction in life expectancy. Cardiovascular diseases remained the major cause of death. Only a few large population studies were conducted in Russia during this period. A total of 1968 men and 1737 women aged 18–75 years participated in a health survey in Arkhangelsk, Russia, over the period 1999–2000. Investigation included assessment of classic cardiovascular risk factors (family history, smoking, blood pressure, and blood lipids) along with general health variables. The paper presents sex specific data on risk factors for coronary heart disease. Though the cardiovascular mortality is high in Russia, the calculated risk for coronary heart disease (the Framingham risk score and the Norwegian risk score) was lower in all age groups of men and women in Arkhangelsk compared with studies from the Western Europe and USA. Our data suggest that high cardiovascular mortality in Russia may be driven not only by the classic risk factors for coronary heart disease.\",\n \"title\": \"High cardiovascular mortality in Russia cannot be explained by the classical risk factors. The Arkhangelsk study 2000\"\n },\n {\n \"docid\": \"752423\",\n \"text\": \"BACKGROUND A reduction in compliance of the large-sized cardiothoracic (central) arteries is an independent risk factor for the development of cardiovascular disease with advancing age. METHODS AND RESULTS We determined the role of habitual exercise on the age-related decrease in central arterial compliance by using both cross-sectional and interventional approaches. First, we studied 151 healthy men aged 18 to 77 years: 54 were sedentary, 45 were recreationally active, and 53 were endurance exercise-trained. Central arterial compliance (simultaneous B-mode ultrasound and arterial applanation tonometry on the common carotid artery) was lower (P:<0.05) in middle-aged and older men than in young men in all 3 groups. There were no significant differences between sedentary and recreationally active men at any age. However, arterial compliance in the endurance-trained middle-aged and older men was 20% to 35% higher than in the 2 less active groups (P:<0.01). As such, age-related differences in central arterial compliance were smaller in the endurance-trained men than in the sedentary and recreationally active men. Second, we studied 20 middle-aged and older (53+/-2 years) sedentary healthy men before and after a 3-month aerobic exercise intervention (primarily walking). Regular exercise increased central arterial compliance (P:<0.01) to levels similar to those of the middle-aged and older endurance-trained men. These effects were independent of changes in body mass, adiposity, arterial blood pressure, or maximal oxygen consumption. CONCLUSIONS Regular aerobic-endurance exercise attenuates age-related reductions in central arterial compliance and restores levels in previously sedentary healthy middle-aged and older men. This may be one mechanism by which habitual exercise lowers the risk of cardiovascular disease in this population.\",\n \"title\": \"Aging, habitual exercise, and dynamic arterial compliance.\"\n },\n {\n \"docid\": \"75636923\",\n \"text\": \"Metabolic syndrome is diagnosed when three or more of the following criteria are met: abdominal obesity (waist circumference more than 102 cm in men and 88 cm in women); hypertriglyceridemia of 150 mg/dl or above; a high-density lipoprotein (HDL) cholesterol level less than 40 mg/dl in men or 50 mg/dl in women; blood pressure of 130/85 mm Hg or higher; or fasting glucose of at least 110 mg/dl. Individuals with metabolic syndrome are likelier than others to develop diabetes and cardiovascular disease and have increased mortality from all causes (and from cardiovascular disease in particular). The investigators attempted to determine the prevalence of the syndrome in the United States by analyzing data on 8814 men and women 20 years of age or older who took part in the Third National Health and Nutrition Examination Survey in the years 1988 to 1994. This is a cross-sectional health survey of a sample of the noninstitutionalized civilian American population. The overall age-adjusted prevalence of metabolic syndrome was 23.7%. The prevalence rose from 6.7% in persons 20 to 29 years of age to 42% in those aged 70 years and more. There was virtually no gender-related difference in prevalence rates for the combined racial groups. Metabolic syndrome was most prevalent in Mexican Americans and least prevalent in whites, African Americans, and \\\"others. \\\" Among both African Americans and Mexican Americans, women had higher prevalence rates than men. Extrapolating from age-specific prevalence rates and US census counts from the year 2000, 47 million US residents have metabolic syndrome. Considering its prevalence, it seems important to estimate the direct medical costs of metabolic syndrome. In the great majority of cases the critical causes are improper nutrition and insufficient physical activity, emphasizing the importance of controlling obesity and encouraging physical activity in the United States.\",\n \"title\": \"Prevalence of the Metabolic Syndrome Among Us Adults: Findings From the Third National Health and Nutrition Examination Survey\"\n },\n {\n \"docid\": \"3413083\",\n \"text\": \"BACKGROUND Following widespread rollout of chlamydia testing to non-specialist and community settings in the UK, many individuals receive a chlamydia test without being offered comprehensive STI and HIV testing. We assess sexual behaviour among testers in different settings with a view to understanding their need for other STI diagnostic services. METHODS A probability sample survey of the British population undertaken 2010-2012 (the third National Survey of Sexual Attitudes and Lifestyles). We analysed weighted data on chlamydia testing (past year), including location of most recent test, and diagnoses (past 5 years) from individuals aged 16-44 years reporting at least one sexual partner in the past year (4992 women, 3406 men). RESULTS Of the 26.8% (95% CI 25.4% to 28.2%) of women and 16.7% (15.5% to 18.1%) of men reporting a chlamydia test in the past year, 28.4% of women and 41.2% of men had tested in genitourinary medicine (GUM), 41.1% and 20.7% of women and men respectively tested in general practice (GP) and the remainder tested in other non-GUM settings. Women tested outside GUM were more likely to be older, in a relationship and to live in rural areas. Individuals tested outside GUM reported fewer risk behaviours; nevertheless, 11.0% (8.6% to 14.1%) of women and 6.8% (3.9% to 11.6%) of men tested in GP and 13.2% (10.2% to 16.8%) and 9.6% (6.5% to 13.8%) of women and men tested in other non-GUM settings reported 'unsafe sex', defined as two or more partners and no condom use with any partner in the past year. Individuals treated for chlamydia outside GUM in the past 5 years were less likely to report an HIV test in that time frame (women: 54.5% (42.7% to 65.7%) vs 74.1% (65.9% to 80.9%) in GUM; men: 23.9% (12.7% to 40.5%) vs 65.8% (56.2% to 74.3%)). CONCLUSIONS Most chlamydia testing occurred in non-GUM settings, among populations reporting fewer risk behaviours. However, there is a need to provide pathways to comprehensive STI care to the sizeable minority at higher risk.\",\n \"title\": \"Patterns of chlamydia testing in different settings and implications for wider STI diagnosis and care: a probability sample survey of the British population\"\n },\n {\n \"docid\": \"17124832\",\n \"text\": \"CONTEXT Previous studies indicate that the population attributable risk (PAR) of bladder cancer for tobacco smoking is 50% to 65% in men and 20% to 30% in women and that current cigarette smoking triples bladder cancer risk relative to never smoking. During the last 30 years, incidence rates have remained stable in the United States in men (123.8 per 100,000 person-years to 142.2 per 100,000 person-years) and women (32.5 per 100,000 person-years to 33.2 per 100,000 person-years); however, changing smoking prevalence and cigarette composition warrant revisiting risk estimates for smoking and bladder cancer. OBJECTIVE To evaluate the association between tobacco smoking and bladder cancer. DESIGN, SETTING, AND PARTICIPANTS Men (n = 281,394) and women (n = 186,134) of the National Institutes of Health-AARP (NIH-AARP) Diet and Health Study cohort completed a lifestyle questionnaire and were followed up between October 25, 1995, and December 31, 2006. Previous prospective cohort studies of smoking and incident bladder cancer were identified by systematic review and relative risks were estimated from fixed-effects models with heterogeneity assessed by the I(2) statistic. MAIN OUTCOME MEASURES Hazard ratios (HRs), PARs, and number needed to harm (NNH). RESULTS During 4,518,941 person-years of follow-up, incident bladder cancer occurred in 3896 men (144.0 per 100,000 person-years) and 627 women (34.5 per 100,000 person-years). Former smokers (119.8 per 100,000 person-years; HR, 2.22; 95% confidence interval [CI], 2.03-2.44; NNH, 1250) and current smokers (177.3 per 100,000 person-years; HR, 4.06; 95% CI, 3.66-4.50; NNH, 727) had higher risks of bladder cancer than never smokers (39.8 per 100,000 person-years). In contrast, the summary risk estimate for current smoking in 7 previous studies (initiated between 1963 and 1987) was 2.94 (95% CI, 2.45-3.54; I(2) = 0.0%). The PAR for ever smoking in our study was 0.50 (95% CI, 0.45-0.54) in men and 0.52 (95% CI, 0.45-0.59) in women. CONCLUSION Compared with a pooled estimate of US data from cohorts initiated between 1963 and 1987, relative risks for smoking in the more recent NIH-AARP Diet and Health Study cohort were higher, with PARs for women comparable with those for men.\",\n \"title\": \"Association between smoking and risk of bladder cancer among men and women.\"\n },\n {\n \"docid\": \"1711571\",\n \"text\": \"PURPOSE Patients with type 2 diabetes mellitus (T2DM) have an increased fracture risk despite having higher areal bone mineral density (aBMD). This study aimed to clarify the association between glycemic and insulin resistance status and bone microarchitecture, and whether pentosidine and bone turnover markers play any roles in the association. METHODS A total of 2012 community-dwelling men aged ≥65years completed baseline measurements of spine aBMD, fasting plasma glucose (FPG) and serum insulin, hemoglobin A1c (HbA1c), osteocalcin, type I procollagen N-terminal propeptide, type I collagen C-terminal crosslinking telopeptide, tartrate-resistant acid phosphatase isoenzyme 5b, pentosidine, height and weight and an interview regarding past disease history. Homeostasis model assessment-insulin resistance (HOMA-IR) was also calculated. T2DM was defined as physician-diagnosed middle age or elderly-onset diabetes mellitus, or according to biochemical test results. To evaluate bone microarchitecture, trabecular bone score (TBS) was calculated at the same vertebrae as those used for aBMD measurement. RESULTS After excluding participants who had a disease history and/or were taking medications affecting bone metabolism, 1683 men (age, 72.9±5.2years) were analyzed. Men with T2DM had significantly higher aBMD compared to those without T2DM. There was no significant difference in TBS. However, FPG, HbA1c and HOMA-IR levels were significantly inversely correlated with TBS after adjusting for age, BMI and aBMD. Multivariate linear regression analyses revealed that glycemic indices (FPG and HbA1c) were significantly associated with increased aBMD and decreased TBS, and that HOMA-IR was associated only with TBS. These associations did not change after further adjusting for bone turnover makers and pentosidine levels. CONCLUSIONS Hyperglycemia and elevated insulin-resistance were associated with low TBS independently of bone turnover and pentosidine levels.\",\n \"title\": \"Hyperglycemia is associated with increased bone mineral density and decreased trabecular bone score in elderly Japanese men: The Fujiwara-kyo osteoporosis risk in men (FORMEN) study.\"\n },\n {\n \"docid\": \"409280\",\n \"text\": \"BACKGROUND Few data have evaluated physician adherence to cardiovascular disease (CVD) prevention guidelines according to physician specialty or patient characteristics, particularly gender. METHODS AND RESULTS An online study of 500 randomly selected physicians (300 primary care physicians, 100 obstetricians/gynecologists, and 100 cardiologists) used a standardized questionnaire to assess awareness of, adoption of, and barriers to national CVD prevention guidelines by specialty. An experimental case study design tested physician accuracy and determinants of CVD risk level assignment and application of guidelines among high-, intermediate-, or low-risk patients. Intermediate-risk women, as assessed by the Framingham risk score, were significantly more likely to be assigned to a lower-risk category by primary care physicians than men with identical risk profiles (P<0.0001), and trends were similar for obstetricians/gynecologists and cardiologists. Assignment of risk level significantly predicted recommendations for lifestyle and preventive pharmacotherapy. After adjustment for risk assignment, the impact of patient gender on preventive care was not significant except for less aspirin (P<0.01) and more weight management recommended (P<0.04) for intermediate-risk women. Physicians did not rate themselves as very effective in their ability to help patients prevent CVD. Fewer than 1 in 5 physicians knew that more women than men die each year from CVD. CONCLUSIONS Perception of risk was the primary factor associated with CVD preventive recommendations. Gender disparities in recommendations for preventive therapy were explained largely by the lower perceived risk despite similar calculated risk for women versus men. Educational interventions for physicians are needed to improve the quality of CVD preventive care and lower morbidity and mortality from CVD for men and women.\",\n \"title\": \"National study of physician awareness and adherence to cardiovascular disease prevention guidelines.\"\n },\n {\n \"docid\": \"5939172\",\n \"text\": \"PURPOSE To analyze the relationship between an aspect of drinking pattern (i.e., drinking with or without meals) and risk of all-cause and specific-cause mortality. METHODS The Risk Factors and Life Expectancy Study, is a pooling of a series of epidemiological studies conducted in Italy. Eight-thousand six-hundred and forty-seven men and 6521 women, age 30-59 at baseline, and free of cardiovascular disease, were followed for mortality from all causes, cardiovascular and noncardiovascular, during an average follow-up of 7 years. RESULTS Drinkers of wine outside meals exhibited higher death rates from all causes, noncardiovascular diseases, and cancer, as compared to drinkers of wine with meals. This association was independent from the cardiovascular disease (CVD) risk factors measured at baseline and the amount of alcohol consumed and seemed to be stronger in women as compared to men. CONCLUSIONS The present results indicate that drinking patterns may have important health implications, and attention should be given to this aspect of alcohol use and its relationship to health outcomes. The relationship between alcohol consumption and disease has been the focus of intensive scientific investigation (1-9). Most studies to date, however, have limitations. A major drawback is that limited information has been collected regarding the complex issue of alcohol consumption. In many studies, ascertainment of alcohol consumption frequently focused only on quantity of alcohol consumed without considering the many different components of alcohol consumption, particularly drinking pattern (10-12). It has been hypothesized, and preliminary data support the notion, that drinking pattern could have important influences on determining the health effects of alcohol (13,14). The present study examines the relationship between one aspect of drinking pattern (drinking wine outside meals) and mortality in a large cohort of men and women.\",\n \"title\": \"Drinking pattern and mortality: the Italian Risk Factor and Life Expectancy pooling project.\"\n },\n {\n \"docid\": \"23785605\",\n \"text\": \"BACKGROUND Migraine, particularly with aura, is a risk factor for early-onset ischemic stroke. The underlying mechanisms are unknown, but may in part be due to migraineurs having an increased risk profile for cardiovascular disease. In this study, the authors compare the cardiovascular risk profile of adult migraineurs to that of nonmigraineurs. METHODS Participants (n = 5,755, 48% men, age 20 to 65 years) are from the Genetic Epidemiology of Migraine (GEM) study, a population-based study in the Netherlands. A total of 620 current migraineurs were identified: 31% with aura (MA), 64% without aura (MO), and 5% unclassified. Controls were 5,135 individuals without lifetime migraine. Measured cardiovascular risk factors included blood pressure (BP), serum total and high-density lipoprotein cholesterol (TC, HDL), smoking, oral contraceptive use, and the Framingham risk score for myocardial infarction or coronary heart disease (CHD) death. RESULTS Compared to controls, migraineurs were more likely to smoke (OR = 1.43 [1.1 to 1.8]), less likely to consume alcohol (OR = 0.58 [0.5 to 0.7]), and more likely to report a parental history of early myocardial infarction. Migraineurs with aura were more likely to have an unfavorable cholesterol profile (TC > or = 240 mg/dL [OR = 1.43 (0.97 to 2.1)], TC:HDL ratio > 5.0 [OR = 1.64 (1.1 to 2.4)]), have elevated BP (systolic BP > 140 mm Hg or diastolic BP > 90 mm Hg [OR = 1.76 (1.04 to 3.0)]), and report a history of early onset CHD or stroke (OR = 3.96 [1.1 to 14.3]); female migraineurs with aura were more likely to be using oral contraceptives (OR = 2.06 [1.05 to 4.0]). The odds of having an elevated Framingham risk score for CHD were approximately doubled for the migraineurs with aura. CONCLUSIONS Migraineurs, particularly with aura, have a higher cardiovascular risk profile than individuals without migraine.\",\n \"title\": \"Cardiovascular risk factors and migraine: the GEM population-based study.\"\n },\n {\n \"docid\": \"43629704\",\n \"text\": \"BACKGROUND Lowering the blood cholesterol level may reduce the risk of coronary heart disease. This double-blind study was designed to determine whether the administration of pravastatin to men with hypercholesterolemia and no history of myocardial infarction reduced the combined incidence of nonfatal myocardial infarction and death from coronary heart disease. METHODS We randomly assigned 6595 men, 45 to 64 years of age, with a mean (+/- SD) plasma cholesterol level of 272 +/- 23 mg per deciliter (7.0 +/- 0.6 mmol per liter) to receive pravastatin (40 mg each evening) or placebo. The average follow-up period was 4.9 years. Medical records, electrocardiographic recordings, and the national death registry were used to determine the clinical end points. RESULTS Pravastatin lowered plasma cholesterol levels by 20 percent and low-density-lipoprotein cholesterol levels by 26 percent, whereas there was no change with placebo. There were 248 definite coronary events (specified as nonfatal myocardial infarction or death from coronary heart disease) in the placebo group, and 174 in the pravastatin group (relative reduction in risk with pravastatin, 31 percent; 95 percent confidence interval, 17 to 43 percent; P < 0.001). There were similar reductions in the risk of definite nonfatal myocardial infarctions (31 percent reduction, P < 0.001), death from coronary heart disease (definite cases alone: 28 percent reduction, P = 0.13; definite plus suspected cases: 33 percent reduction, P = 0.042), and death from all cardiovascular causes (32 percent reduction, P = 0.033). There was no excess of deaths from noncardiovascular causes in the pravastatin group. We observed a 22 percent reduction in the risk of death from any cause in the pravastatin group (95 percent confidence interval, 0 to 40 percent; P = 0.051). CONCLUSIONS Treatment with pravastatin significantly reduced the incidence of myocardial infarction and death from cardiovascular causes without adversely affecting the risk of death from noncardiovascular causes in men with moderate hypercholesterolemia and no history of myocardial infarction.\",\n \"title\": \"Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group.\"\n },\n {\n \"docid\": \"18199839\",\n \"text\": \"BACKGROUND Persistent inflammation has been proposed to contribute to various stages in the pathogenesis of cardiovascular disease. Interleukin-6 receptor (IL6R) signalling propagates downstream inflammation cascades. To assess whether this pathway is causally relevant to coronary heart disease, we studied a functional genetic variant known to affect IL6R signalling. METHODS In a collaborative meta-analysis, we studied Asp358Ala (rs2228145) in IL6R in relation to a panel of conventional risk factors and inflammation biomarkers in 125,222 participants. We also compared the frequency of Asp358Ala in 51,441 patients with coronary heart disease and in 136,226 controls. To gain insight into possible mechanisms, we assessed Asp358Ala in relation to localised gene expression and to postlipopolysaccharide stimulation of interleukin 6. FINDINGS The minor allele frequency of Asp358Ala was 39%. Asp358Ala was not associated with lipid concentrations, blood pressure, adiposity, dysglycaemia, or smoking (p value for association per minor allele ≥0·04 for each). By contrast, for every copy of 358Ala inherited, mean concentration of IL6R increased by 34·3% (95% CI 30·4-38·2) and of interleukin 6 by 14·6% (10·7-18·4), and mean concentration of C-reactive protein was reduced by 7·5% (5·9-9·1) and of fibrinogen by 1·0% (0·7-1·3). For every copy of 358Ala inherited, risk of coronary heart disease was reduced by 3·4% (1·8-5·0). Asp358Ala was not related to IL6R mRNA levels or interleukin-6 production in monocytes. INTERPRETATION Large-scale human genetic and biomarker data are consistent with a causal association between IL6R-related pathways and coronary heart disease. FUNDING British Heart Foundation; UK Medical Research Council; UK National Institute of Health Research, Cambridge Biomedical Research Centre; BUPA Foundation.\",\n \"title\": \"Interleukin-6 receptor pathways in coronary heart disease: a collaborative meta-analysis of 82 studies\"\n },\n {\n \"docid\": \"2052720\",\n \"text\": \"OBJECTIVE To investigate the association between gastric cancer and prior infection with Helicobacter pylori. DESIGN Case-control comparison of prevalence of IgG antibodies to H pylori in blood samples collected prospectively, before diagnosis of gastric cancer in the cases. Presence of H pylori antibody (greater than 10 micrograms IgG/ml) determined by enzyme linked immunosorbent assay (ELISA). SUBJECTS 29 men with a subsequent diagnosis of gastric cancer and 116 aged matched controls selected from over 22,000 middle aged men participating in two ongoing cohort studies (the British United Provident Association study and the Caerphilly collaborative heart disease study), who had provided blood samples during 1975-1982. RESULTS 20 of the 29 cases (69%) and 54 of the 116 controls (47%) were positive for H pylori specific antibody. The median specific IgG concentration was significantly higher in the cases than controls (90 micrograms/ml v 3.6 micrograms/ml, p less than 0.01). The estimated odds ratio for the risk of gastric cancer in those with a history of infection with H pylori was 2.77 (95% confidence interval 1.04 to 7.97, 2p = 0.039). CONCLUSIONS H pylori infection may be an important cause of gastric cancer; between 35% and 55% of all cases may be associated with such an infection.\",\n \"title\": \"Association between infection with Helicobacter pylori and risk of gastric cancer: evidence from a prospective investigation.\"\n },\n {\n \"docid\": \"15925931\",\n \"text\": \"BACKGROUND Whole-body magnetic resonance angiography (WB-MRA) has shown its potential for the non-invasive assessment of nearly the entire arterial vasculature within one examination. Since the presence of extra-cardiac atherosclerosis is associated with an increased risk of coronary events, our goal was to establish the relationship between WB-MRA findings, including a systemic atherosclerosis score index, and the presence of significant coronary artery disease (CAD). METHODS WB-MRA was performed on a 1.5T scanner in 50 patients scheduled to undergo elective cardiac catheterization for suspected CAD. In each patient, 40 extra-cardiac vessel segments were evaluated and assigned scores according to their luminal narrowing. The atherosclerosis score index (ASI) was generated as the ratio of summed scores to analyzable segments. RESULTS ASI was higher in patients with significant (> 50% stenosis) CAD (n = 27) vs. patients without CAD (n = 22; 1.56 vs. 1.28, p = 0.004). ASI correlated with PROCAM (R = 0.57, p < 0.001) and Framingham (R = 0.36, p = 0.01) risk scores as estimates of the 10-year risk of coronary events. A ROC derived ASI of > 1.54 predicted significant CAD with a sensitivity of 59%, specificity of 86% and a positive predictive value of 84%. Logistic regression revealed ASI > 1.54 as the strongest independent predictor for CAD with a 11-fold increase in likelihood to suffer from significant coronary disease. On the contrary, while 15/27 (55%) of patients with CAD exhibited at least one extra-cardiac stenosis > 50%, only 3/22 (14%) of those patients without CAD did (p = 0.003). The likelihood for an extra-cardiac stenosis when CAD is present differed between vascular territories and ranged from 15% for a carotid stenosis to 44% for a stenosis in the lower extremities. CONCLUSION This study provides important new evidence for the close association of extra-cardiac and coronary atherosclerosis. The novel findings that a WB-MRA derived systemic atherosclerosis score index is not only associated with established cardiovascular risk scores but is also predictive of significant CAD suggest its potential prognostic implications and underline the importance to screen for coronary disease in patients with extra-cardiac manifestations of atherosclerosis.\",\n \"title\": \"Prediction of coronary artery disease by a systemic atherosclerosis score index derived from whole-body MR angiography\"\n },\n {\n \"docid\": \"16252863\",\n \"text\": \"The list of preventable and reversible risk factors for atherosclerotic cardiovascular disease continues to grow. Cigarette smoking, high blood pressure, physical inactivity, elevated cholesterol, underlying lipoprotein abnormalities, lipoprotein(a), diabetes, overweight, male gender, and age are well-established risk factors. During the 1990s, there have been many reports associating elevated plasma homocysteine levels with arteriosclerotic cardiovascular disease and consistent evidence that dietary and supplemental folic acid can reduce homocysteine levels.1 2 The article by Robinson and colleagues3 in this issue of Circulation presents further evidence of the importance of homocysteine and suggestive evidence that plasma folate and plasma pyrixodal-l-phosphate (vitamin B6) are protective factors. Their study is part of the European Concerted Action Project,4 which examined 750 patients younger than age 60 with diagnoses within the previous 12 months of coronary, cerebrovascular, or peripheral vascular disease and 800 healthy control subjects. The patient groups were young (47 years for cases and 44 years for control subjects) and heterogeneous, with nonfatal clinical events or symptoms of arteriosclerotic cardiovascular disease supported by ECG, angiographic, or Doppler evidence; the study involved 19 centers in nine European countries. Men in the highest quintile for fasting total homocysteine (tHcy), compared with the remainder of the population, had an estimated relative risk of 2.2 (95% confidence interval [CI], 1.6 to 2.9), with a striking dose-response relationship and a more-than-multiplicative interaction with cigarette smoking and high blood pressure on vascular disease risk4 ; the corresponding estimated relative risk for coronary heart disease was similar (2.0; 95% CI 1.6 to 2.8). (tHcy is the sum of homocysteine and homocysteinyl moieties of oxidized disulfides, homocystine, and cysteine- homocysteine. ) Robinson and colleagues3 examined three B vitamins in detail to determine their effects on fasting and post–methionine-loading tHcy levels and any independent effects on cardiovascular disease …\",\n \"title\": \"Preventing coronary heart disease: B vitamins and homocysteine.\"\n },\n {\n \"docid\": \"44624045\",\n \"text\": \"BACKGROUND Few previous prospective studies have examined differences in incident ischemic heart disease (IHD) risk between vegetarians and nonvegetarians. OBJECTIVE The objective was to examine the association of a vegetarian diet with risk of incident (nonfatal and fatal) IHD. DESIGN A total of 44,561 men and women living in England and Scotland who were enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Oxford study, of whom 34% consumed a vegetarian diet at baseline, were part of the analysis. Incident cases of IHD were identified through linkage with hospital records and death certificates. Serum lipids and blood pressure measurements were available for 1519 non cases, who were matched to IHD cases by sex and age. IHD risk by vegetarian status was estimated by using multivariate Cox proportional hazards models. RESULTS After an average follow-up of 11.6 y, there were 1235 IHD cases (1066 hospital admissions and 169 deaths). Compared with nonvegetarians, vegetarians had a lower mean BMI [in kg/m(2); -1.2 (95% CI: -1.3, -1.1)], non-HDL-cholesterol concentration [-0.45 (95% CI: -0.60, -0.30) mmol/L], and systolic blood pressure [-3.3 (95% CI: -5.9, -0.7) mm Hg]. Vegetarians had a 32% lower risk (HR: 0.68; 95% CI: 0.58, 0.81) of IHD than did nonvegetarians, which was only slightly attenuated after adjustment for BMI and did not differ materially by sex, age, BMI, smoking, or the presence of IHD risk factors. CONCLUSION Consuming a vegetarian diet was associated with lower IHD risk, a finding that is probably mediated by differences in non-HDL cholesterol, and systolic blood pressure.\",\n \"title\": \"Risk of hospitalization or death from ischemic heart disease among British vegetarians and nonvegetarians: results from the EPIC-Oxford cohort study.\"\n },\n {\n \"docid\": \"45027320\",\n \"text\": \"BACKGROUND The aim of this study was to examine the clustering of four major lifestyle risk factors (smoking, heavy drinking, lack of fruit and vegetables consumption, and lack of physical activity), and to examine the variation across different socio-demographic groups in the English adult population. METHODS The study population was derived from the 2003 Health Survey for England (n=11,492). Clustering was examined by comparing the observed and expected prevalence of the different possible combinations. A multinomial multilevel regression model was conducted to examine the socio-demographic variation in the clustering of the four risk factors. RESULTS The study found that, when using British health recommendations, a majority of the English population have multiple lifestyle risk factors at the same time. Clustering was found at both ends of the lifestyle spectrum and was more pronounced for women than for men. Overall, multiple risk factors were more prevalent among men, lower social class households, singles, and people who are economically inactive, but less prevalent among home owners and older age groups. CONCLUSIONS The clustering of multiple risk factors provides support for multiple-behavior interventions as opposed to single-behavior interventions.\",\n \"title\": \"The prevalence and clustering of four major lifestyle risk factors in an English adult population.\"\n },\n {\n \"docid\": \"6327940\",\n \"text\": \"Amino acids modulate the secretion of both insulin and glucagon; the composition of dietary protein therefore has the potential to influence the balance of glucagon and insulin activity. Soy protein, as well as many other vegan proteins, are higher in non-essential amino acids than most animal-derived food proteins, and as a result should preferentially favor glucagon production. Acting on hepatocytes, glucagon promotes (and insulin inhibits) cAMP-dependent mechanisms that down-regulate lipogenic enzymes and cholesterol synthesis, while up-regulating hepatic LDL receptors and production of the IGF-I antagonist IGFBP-1. The insulin-sensitizing properties of many vegan diets--high in fiber, low in saturated fat--should amplify these effects by down-regulating insulin secretion. Additionally, the relatively low essential amino acid content of some vegan diets may decrease hepatic IGF-I synthesis. Thus, diets featuring vegan proteins can be expected to lower elevated serum lipid levels, promote weight loss, and decrease circulating IGF-I activity. The latter effect should impede cancer induction (as is seen in animal studies with soy protein), lessen neutrophil-mediated inflammatory damage, and slow growth and maturation in children. In fact, vegans tend to have low serum lipids, lean physiques, shorter stature, later puberty, and decreased risk for certain prominent 'Western' cancers; a vegan diet has documented clinical efficacy in rheumatoid arthritis. Low-fat vegan diets may be especially protective in regard to cancers linked to insulin resistance--namely, breast and colon cancer--as well as prostate cancer; conversely, the high IGF-I activity associated with heavy ingestion of animal products may be largely responsible for the epidemic of 'Western' cancers in wealthy societies. Increased phytochemical intake is also likely to contribute to the reduction of cancer risk in vegans. Regression of coronary stenoses has been documented during low-fat vegan diets coupled with exercise training; such regimens also tend to markedly improve diabetic control and lower elevated blood pressure. Risk of many other degenerative disorders may be decreased in vegans, although reduced growth factor activity may be responsible for an increased risk of hemorrhagic stroke. By altering the glucagon/insulin balance, it is conceivable that supplemental intakes of key non-essential amino acids could enable omnivores to enjoy some of the health advantages of a vegan diet. An unnecessarily high intake of essential amino acids--either in the absolute sense or relative to total dietary protein--may prove to be as grave a risk factor for 'Western' degenerative diseases as is excessive fat intake.\",\n \"title\": \"Vegan proteins may reduce risk of cancer, obesity, and cardiovascular disease by promoting increased glucagon activity.\"\n },\n {\n \"docid\": \"5884524\",\n \"text\": \"BACKGROUND Although unstable coronary artery disease is the most common reason for admission to a coronary care unit, the long-term prognosis of patients with this diagnosis is unknown. This is particularly true for patients with diabetes mellitus, who are known to have a high morbidity and mortality after an acute myocardial infarction. METHODS AND RESULTS Prospectively collected data from 6 different countries in the Organization to Assess Strategies for Ischemic Syndromes (OASIS) registry were analyzed to determine the 2-year prognosis of diabetic and nondiabetic patients who were hospitalized with unstable angina or non-Q-wave myocardial infarction. Overall, 1718 of 8013 registry patients (21%) had diabetes. Diabetic patients had a higher rate of coronary bypass surgery than nondiabetic patients (23% versus 20%, P:<0.001) but had similar rates of catheterization and angioplasty. Diabetes independently predicted mortality (relative risk [RR], 1.57; 95% CI, 1.38 to 1.81; P:<0.001), as well as cardiovascular death, new myocardial infarction, stroke, and new congestive heart failure. Moreover, compared with their nondiabetic counterparts, women had a significantly higher risk than men (RR, 1.98; 95% CI, 1.60 to 2.44; and RR, 1.28; 95% CI, 1.06 to 1.56, respectively). Interestingly, diabetic patients without prior cardiovascular disease had the same event rates for all outcomes as nondiabetic patients with previous vascular disease. CONCLUSIONS Hospitalization for unstable angina or non-Q-wave myocardial infarction predicts a high 2-year morbidity and mortality; this is especially evident for patients with diabetes. Diabetic patients with no previous cardiovascular disease have the same long-term morbidity and mortality as nondiabetic patients with established cardiovascular disease after hospitalization for unstable coronary artery disease.\",\n \"title\": \"Impact of diabetes on long-term prognosis in patients with unstable angina and non-Q-wave myocardial infarction: results of the OASIS (Organization to Assess Strategies for Ischemic Syndromes) Registry.\"\n },\n {\n \"docid\": \"9617381\",\n \"text\": \"OBJECTIVE To evaluate long-term prognostic effect of serum noncholesterol sterols, including plant sterols, in middle-aged men with high cardiovascular disease (CVD) risk, without statins at baseline. METHODS This was a prospective study of 232 men (mean age 60 years) at high risk of CVD in 1985-1986. Most were hypercholesterolemic, 29 (12%) had a history of CVD or cancer, 6 (3%) had diabetes, and 46 (20%) had metabolic syndrome (MS). Measured noncholesterol sterols (expressed as absolute concentrations or ratios to serum cholesterol to standardize for cholesterol concentrations) included lathosterol and desmosterol (reflect cholesterol synthesis), and plant sterols (campesterol and sitosterol) and cholestanol (reflect cholesterol absorption). Main outcome measure was total mortality. RESULTS At baseline, markers of cholesterol synthesis and absorption showed expected inverse associations. During the 22-year follow-up 101 men (43%) died. At baseline, nonsurvivors smoked more, exercised less and had more components of MS (although not filling strict criteria), whereas traditional risk factors of CVD were not significantly different. Of the noncholesterol sterols (either absolute or ratio), only sitosterol was significantly higher in survivors than in nonsurvivors (P=0.02). In multivariable analyses, highest sitosterol-to-cholesterol tertile was associated with significantly lower mortality risk (HR 0.51, 95% CI 0.30-0.87) as compared to lowest tertile. Other associations were nonsignificant, although a \\\"global\\\" index of cholesterol metabolism (desmosterol-to-sitosterol ratio) suggested higher cholesterol synthesis and lower absorption to be associated with higher total and CVD mortality. CONCLUSION Higher serum plant sterol levels in middle-aged men predicted lower long-term mortality risk, possibly reflecting an association between higher synthesis/lower absorption of cholesterol and mortality.\",\n \"title\": \"Serum plant and other noncholesterol sterols, cholesterol metabolism and 22-year mortality among middle-aged men.\"\n }\n]"}}},{"rowIdx":193,"cells":{"query_id":{"kind":"string","value":"69"},"query":{"kind":"string","value":"Activation of PPM1D enhances p53 function."},"positive_passages":{"kind":"list like","value":[{"docid":"4414547","text":"Improved sequencing technologies offer unprecedented opportunities for investigating the role of rare genetic variation in common disease. However, there are considerable challenges with respect to study design, data analysis and replication. Using pooled next-generation sequencing of 507 genes implicated in the repair of DNA in 1,150 samples, an analytical strategy focused on protein-truncating variants (PTVs) and a large-scale sequencing case–control replication experiment in 13,642 individuals, here we show that rare PTVs in the p53-inducible protein phosphatase PPM1D are associated with predisposition to breast cancer and ovarian cancer. PPM1D PTV mutations were present in 25 out of 7,781 cases versus 1 out of 5,861 controls (P = 1.12 × 10−5), including 18 mutations in 6,912 individuals with breast cancer (P = 2.42 × 10−4) and 12 mutations in 1,121 individuals with ovarian cancer (P = 3.10 × 10−9). Notably, all of the identified PPM1D PTVs were mosaic in lymphocyte DNA and clustered within a 370-base-pair region in the final exon of the gene, carboxy-terminal to the phosphatase catalytic domain. Functional studies demonstrate that the mutations result in enhanced suppression of p53 in response to ionizing radiation exposure, suggesting that the mutant alleles encode hyperactive PPM1D isoforms. Thus, although the mutations cause premature protein truncation, they do not result in the simple loss-of-function effect typically associated with this class of variant, but instead probably have a gain-of-function effect. Our results have implications for the detection and management of breast and ovarian cancer risk. More generally, these data provide new insights into the role of rare and of mosaic genetic variants in common conditions, and the use of sequencing in their identification.","title":"Mosaic PPM1D mutations are associated with predisposition to breast and ovarian cancer"},{"docid":"5956380","text":"Gliomas arising in the brainstem and thalamus are devastating tumors that are difficult to surgically resect. To determine the genetic and epigenetic landscape of these tumors, we performed exomic sequencing of 14 brainstem gliomas (BSGs) and 12 thalamic gliomas. We also performed targeted mutational analysis of an additional 24 such tumors and genome-wide methylation profiling of 45 gliomas. This study led to the discovery of tumor-specific mutations in PPM1D, encoding wild-type p53-induced protein phosphatase 1D (WIP1), in 37.5% of the BSGs that harbored hallmark H3F3A mutations encoding p. Lys27Met substitutions. PPM1D mutations were mutually exclusive with TP53 mutations in BSG and attenuated p53 activation in vitro. PPM1D mutations were truncating alterations in exon 6 that enhanced the ability of PPM1D to suppress the activation of the DNA damage response checkpoint protein CHK2. These results define PPM1D as a frequent target of somatic mutation and as a potential therapeutic target in brainstem gliomas.","title":"Exome sequencing identifies somatic gain-of-function PPM1D mutations in brainstem gliomas"}],"string":"[\n {\n \"docid\": \"4414547\",\n \"text\": \"Improved sequencing technologies offer unprecedented opportunities for investigating the role of rare genetic variation in common disease. However, there are considerable challenges with respect to study design, data analysis and replication. Using pooled next-generation sequencing of 507 genes implicated in the repair of DNA in 1,150 samples, an analytical strategy focused on protein-truncating variants (PTVs) and a large-scale sequencing case–control replication experiment in 13,642 individuals, here we show that rare PTVs in the p53-inducible protein phosphatase PPM1D are associated with predisposition to breast cancer and ovarian cancer. PPM1D PTV mutations were present in 25 out of 7,781 cases versus 1 out of 5,861 controls (P = 1.12 × 10−5), including 18 mutations in 6,912 individuals with breast cancer (P = 2.42 × 10−4) and 12 mutations in 1,121 individuals with ovarian cancer (P = 3.10 × 10−9). Notably, all of the identified PPM1D PTVs were mosaic in lymphocyte DNA and clustered within a 370-base-pair region in the final exon of the gene, carboxy-terminal to the phosphatase catalytic domain. Functional studies demonstrate that the mutations result in enhanced suppression of p53 in response to ionizing radiation exposure, suggesting that the mutant alleles encode hyperactive PPM1D isoforms. Thus, although the mutations cause premature protein truncation, they do not result in the simple loss-of-function effect typically associated with this class of variant, but instead probably have a gain-of-function effect. Our results have implications for the detection and management of breast and ovarian cancer risk. More generally, these data provide new insights into the role of rare and of mosaic genetic variants in common conditions, and the use of sequencing in their identification.\",\n \"title\": \"Mosaic PPM1D mutations are associated with predisposition to breast and ovarian cancer\"\n },\n {\n \"docid\": \"5956380\",\n \"text\": \"Gliomas arising in the brainstem and thalamus are devastating tumors that are difficult to surgically resect. To determine the genetic and epigenetic landscape of these tumors, we performed exomic sequencing of 14 brainstem gliomas (BSGs) and 12 thalamic gliomas. We also performed targeted mutational analysis of an additional 24 such tumors and genome-wide methylation profiling of 45 gliomas. This study led to the discovery of tumor-specific mutations in PPM1D, encoding wild-type p53-induced protein phosphatase 1D (WIP1), in 37.5% of the BSGs that harbored hallmark H3F3A mutations encoding p. Lys27Met substitutions. PPM1D mutations were mutually exclusive with TP53 mutations in BSG and attenuated p53 activation in vitro. PPM1D mutations were truncating alterations in exon 6 that enhanced the ability of PPM1D to suppress the activation of the DNA damage response checkpoint protein CHK2. These results define PPM1D as a frequent target of somatic mutation and as a potential therapeutic target in brainstem gliomas.\",\n \"title\": \"Exome sequencing identifies somatic gain-of-function PPM1D mutations in brainstem gliomas\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"23985464","text":"Wild-type p53 has recently been shown to repress transcription from several cellular and viral promoters. Since p53 mutations are the most frequently reported genetic defects in human cancers, it becomes important to study the effects of mutations of p53 on promoter functions. We, therefore, have studied the effects of wild-type and mutant human p53 on the human proliferating-cell nuclear antigen (PCNA) promoter and on several viral promoters, including the herpes simplex virus type 1 UL9 promoter, the human cytomegalovirus major immediate-early promoter-enhancer, and the long terminal repeat promoters of Rous sarcoma virus and human T-cell lymphotropic virus type I. HeLa cells were cotransfected with a wild-type or mutant p53 expression vector and a plasmid containing a chloramphenicol acetyltransferase reporter gene under viral (or cellular) promoter control. As expected, expression of the wild-type p53 inhibited promoter function. Expression of a p53 with a mutation at any one of the four amino acid positions 175, 248, 273, or 281, however, correlated with a significant increase of the PCNA promoter activity (2- to 11-fold). The viral promoters were also activated, although to a somewhat lesser extent. We also showed that activation by a mutant p53 requires a minimal promoter containing a lone TATA box. A more significant increase (25-fold) in activation occurs when the promoter contains a binding site for the activating transcription factor or cyclic AMP response element-binding protein. Using Saos-2 cells that do not express p53, we showed that activation by a mutant p53 was a direct enhancement. The mutant forms of p53 used in this study are found in various cancer cells. The activation of PCNA by mutant p53s may indicate a way to increase cell proliferation by the mutant p53s. Thus, our data indicate a possible functional role for the mutants of p53 found in cancer cells in activating several important loci, including PCNA.","title":"Modulation of cellular and viral promoters by mutant human p53 proteins found in tumor cells."},{"docid":"21307488","text":"HER-2/neu amplification or overexpression can make cancer cells resistant to apoptosis and promotes their growth. p53 is crucial in regulating cell growth and apoptosis, and is often mutated or deleted in many types of tumour. Moreover, many tumours with a wild-type gene for p53 do not have normal p53 function, suggesting that some oncogenic signals suppress the function of p53. In this study, we show that HER-2/neu-mediated resistance to DNA-damaging agents requires the activation of Akt, which enhances MDM2-mediated ubiquitination and degradation of p53. Akt physically associates with MDM2 and phosphorylates it at Ser166 and Ser186. Phosphorylation of MDM2 enhances its nuclear localization and its interaction with p300, and inhibits its interaction with p19ARF, thus increasing p53 degradation. Our study indicates that blocking the Akt pathway mediated by HER-2/neu would increase the cytotoxic effect of DNA-damaging drugs in tumour cells with wild-type p53.","title":"HER-2/neu induces p53 ubiquitination via Akt-mediated MDM2 phosphorylation"},{"docid":"9669099","text":"Binding within or nearby target genes involved in cell proliferation and survival enables the p53 tumor suppressor gene to regulate their transcription and cell-cycle progression. Using genome-wide chromatin-binding profiles, we describe binding of p53 also to regions located distantly from any known p53 target gene. Interestingly, many of these regions possess conserved p53-binding sites and all known hallmarks of enhancer regions. We demonstrate that these p53-bound enhancer regions (p53BERs) indeed contain enhancer activity and interact intrachromosomally with multiple neighboring genes to convey long-distance p53-dependent transcription regulation. Furthermore, p53BERs produce, in a p53-dependent manner, enhancer RNAs (eRNAs) that are required for efficient transcriptional enhancement of interacting target genes and induction of a p53-dependent cell-cycle arrest. Thus, our results ascribe transcription enhancement activity to p53 with the capacity to regulate multiple genes from a single genomic binding site. Moreover, eRNA production from p53BERs is required for efficient p53 transcription enhancement.","title":"eRNAs are required for p53-dependent enhancer activity and gene transcription."},{"docid":"37204802","text":"Jumonji domain-containing 6 (JMJD6) is a member of the Jumonji C domain-containing family of proteins. Compared to other members of the family, the cellular activity of JMJD6 is still not clearly defined and its biological function is still largely unexplored. Here we report that JMJD6 is physically associated with the tumor suppressor p53. We demonstrated that JMJD6 acts as an α-ketoglutarate- and Fe(II)-dependent lysyl hydroxylase to catalyze p53 hydroxylation. We found that p53 indeed exists as a hydroxylated protein in vivo and that the hydroxylation occurs mainly on lysine 382 of p53. We showed that JMJD6 antagonizes p53 acetylation, promotes the association of p53 with its negative regulator MDMX, and represses transcriptional activity of p53. Depletion of JMJD6 enhances p53 transcriptional activity, arrests cells in the G1 phase, promotes cell apoptosis, and sensitizes cells to DNA damaging agent-induced cell death. Importantly, knockdown of JMJD6 represses p53-dependent colon cell proliferation and tumorigenesis in vivo, and significantly, the expression of JMJD6 is markedly up-regulated in various types of human cancer especially in colon cancer, and high nuclear JMJD6 protein is strongly correlated with aggressive clinical behaviors of colon adenocarcinomas. Our results reveal a novel posttranslational modification for p53 and support the pursuit of JMJD6 as a potential biomarker for colon cancer aggressiveness and a potential target for colon cancer intervention.","title":"JMJD6 Promotes Colon Carcinogenesis through Negative Regulation of p53 by Hydroxylation"},{"docid":"14460402","text":"The molecular mechanisms that regulate adult neural precursor cell (NPC) survival, and thus maintain adult neurogenesis, are not well defined. Here, we investigate the role of p63, a p53 family member, in adult NPC function in mice. Conditional ablation of p63 in adult NPCs or p63 haploinsufficiency led to reduced numbers of NPCs and newborn neurons in the neurogenic zones of the hippocampus and lateral ventricles and in the olfactory bulb. These reductions were attributable to enhanced apoptosis of NPCs and newborn neurons and were rescued by inhibition of caspase activity, p53, or the p53 apoptotic effector PUMA (p53-upregulated modulator of apoptosis). Moreover, these cellular deficits were functionally important because they led to perturbations in hippocampus-dependent memory formation. These results indicate that p63 regulates the numbers of adult NPCs and adult-born neurons as well as neural stem cell-dependent cognitive functions, and that it does so, at least in part, by inhibiting p53-dependent cell death.","title":"p63 Regulates adult neural precursor and newly born neuron survival to control hippocampal-dependent Behavior."},{"docid":"11903247","text":"Multiple cellular stressors, including activation of the tumour suppressor p53, can stimulate autophagy. Here we show that deletion, depletion or inhibition of p53 can induce autophagy in human, mouse and nematode cells subjected to knockout, knockdown or pharmacological inhibition of p53. Enhanced autophagy improved the survival of p53-deficient cancer cells under conditions of hypoxia and nutrient depletion, allowing them to maintain high ATP levels. Inhibition of p53 led to autophagy in enucleated cells, and cytoplasmic, not nuclear, p53 was able to repress the enhanced autophagy of p53−/− cells. Many different inducers of autophagy (for example, starvation, rapamycin and toxins affecting the endoplasmic reticulum) stimulated proteasome-mediated degradation of p53 through a pathway relying on the E3 ubiquitin ligase HDM2. Inhibition of p53 degradation prevented the activation of autophagy in several cell lines, in response to several distinct stimuli. These results provide evidence of a key signalling pathway that links autophagy to the cancer-associated dysregulation of p53.","title":"Regulation of autophagy by cytoplasmic p53"},{"docid":"4460880","text":"Endothelial cells contribute to a subset of cardiac fibroblasts by undergoing endothelial-to-mesenchymal transition, but whether cardiac fibroblasts can adopt an endothelial cell fate and directly contribute to neovascularization after cardiac injury is not known. Here, using genetic fate map techniques, we demonstrate that cardiac fibroblasts rapidly adopt an endothelial-cell-like phenotype after acute ischaemic cardiac injury. Fibroblast-derived endothelial cells exhibit anatomical and functional characteristics of native endothelial cells. We show that the transcription factor p53 regulates such a switch in cardiac fibroblast fate. Loss of p53 in cardiac fibroblasts severely decreases the formation of fibroblast-derived endothelial cells, reduces post-infarct vascular density and worsens cardiac function. Conversely, stimulation of the p53 pathway in cardiac fibroblasts augments mesenchymal-to-endothelial transition, enhances vascularity and improves cardiac function. These observations demonstrate that mesenchymal-to-endothelial transition contributes to neovascularization of the injured heart and represents a potential therapeutic target for enhancing cardiac repair.","title":"Mesenchymal-endothelial-transition contributes to cardiac neovascularization"},{"docid":"21521236","text":"In a search for mediators of the p53 tumor suppressor pathway, which induces pleiotropic and often antagonistic cellular responses, we identified the long noncoding RNA (lncRNA) NEAT1. NEAT1 is an essential architectural component of paraspeckle nuclear bodies, whose pathophysiological relevance remains unclear. Activation of p53, pharmacologically or by oncogene-induced replication stress, stimulated the formation of paraspeckles in mouse and human cells. Silencing Neat1 expression in mice, which prevents paraspeckle formation, sensitized preneoplastic cells to DNA-damage-induced cell death and impaired skin tumorigenesis. We provide mechanistic evidence that NEAT1 promotes ATR signaling in response to replication stress and is thereby engaged in a negative feedback loop that attenuates oncogene-dependent activation of p53. NEAT1 targeting in established human cancer cell lines induced synthetic lethality with genotoxic chemotherapeutics, including PARP inhibitors, and nongenotoxic activation of p53. This study establishes a key genetic link between NEAT1 paraspeckles, p53 biology and tumorigenesis and identifies NEAT1 as a promising target to enhance sensitivity of cancer cells to both chemotherapy and p53 reactivation therapy.","title":"p53 induces formation of NEAT1 lncRNA-containing paraspeckles that modulate replication stress response and chemosensitivity"},{"docid":"10015292","text":"Highly regenerative tissues such as blood must possess effective DNA damage responses (DDR) that balance long-term regeneration with protection from leukemogenesis. Hematopoietic stem cells (HSCs) sustain life-long blood production, yet their response to DNA damage remains largely unexplored. We report that human HSCs exhibit delayed DNA double-strand break rejoining, persistent gammaH2AX foci, and enhanced p53- and ASPP1-dependent apoptosis after gamma-radiation compared to progenitors. p53 inactivation or Bcl-2 overexpression reduced radiation-induced apoptosis and preserved in vivo repopulating HSC function. Despite similar protection from irradiation-induced apoptosis, only Bcl-2-overexpressing HSCs showed higher self-renewal capacity, establishing that intact p53 positively regulates self-renewal independently from apoptosis. The reduced self-renewal of HSCs with inactivated p53 was associated with increased spontaneous gammaH2AX foci in secondary transplants of HSCs. Our data reveal distinct physiological roles of p53 that together ensure optimal HSC function: apoptosis regulation and prevention of gammaH2AX foci accumulation upon HSC self-renewal.","title":"A distinctive DNA damage response in human hematopoietic stem cells reveals an apoptosis-independent role for p53 in self-renewal."},{"docid":"35684881","text":"Tumor-derived p53 mutants can transcriptionally activate a number of promoters of genes involved in cellular proliferation. For this transactivation, mutant p53 does not use the wild-type p53 DNA-binding site, suggesting a mechanism of transactivation that is independent of direct DNA binding. Here we describe our analysis of the domain requirements for mutant p53 to transactivate promoters of the human epidermal growth factor receptor (EGFR), human multiple drug resistance 1 (MDR-1) and human proliferating cell nuclear antigen (PCNA) genes. We also report the identification of a structural domain required for the `gain of function' property of mutant p53-281G. `Gain of function' is measured as the tumorigenicity (in nude mice) of 10(3) murine cells expressing mutant p53 constitutively. We have generated internal deletion mutants of p53-281G deleting conserved domains I, II, III, IV and V, individually. We have also generated one deletion mutant eliminating amino acids 100 through 300 that removes four of the five conserved domains (II–V); another mutant, p53-281G del 393-327, deletes the oligomerization and nonsequence-specific nucleic acid-binding domains of p53. For the EGFR and MDR-1 promoters, all these mutants have significantly lower transactivation ability than intact p53-281G. These deletion mutants, however, significantly activated the pCNA promoter, suggesting that the mechanism of transactivation of the PCNA promoter is different from that of the EGFR and MDR-1 promoters. When expressed constitutively in 10(3) cells, p53-281G del 393-327 was found to be defective in inducing tumor formation in nude mice although intact p53-281G was very efficient. Thus, our results suggest that structural domains near the C-terminus are needed for `gain of function'.","title":"`Gain of function' phenotype of tumor-derived mutant p53 requires the oligomerization/nonsequence-specific nucleic acid-binding domain"},{"docid":"9169645","text":"The ability of p53 to induce apoptosis requires its sequence-specific DNA binding activity; however, the transactivation-deficient p53(Gln22-Ser23) can still induce apoptosis. Previously, we have shown that the region between residues 23 and 97 in p53 is necessary for such activity. In an effort to more precisely map a domain necessary for apoptosis within the N terminus, we found that deletion of the N-terminal 23 amino acids compromises, but does not abolish, p53 induction of apoptosis. Surprisingly, p53(Delta1-42), which lacks the N-terminal 42 amino acids and the previously defined activation domain, retains the ability to induce apoptosis to an even higher level than wild-type p53. A more extensive deletion, which eliminates the N-terminal 63 amino acids, renders p53 completely inert in mediating apoptosis. In addition, we found that both p53(Delta1-42) and p53(Gln22-Ser23) can activate a subset of cellular p53 targets. Furthermore, we showed that residues 53 and 54 are critical for the apoptotic and transcriptional activities of both p53(Delta1-42) and p53(Gln22-Ser23). Taken together, these data suggest that within residues 43-63 lie an apoptotic domain as well as another transcriptional activation domain. We therefore postulate that the apoptotic activity in p53(Gln22-Ser23) and p53(Delta1-42) is still transcription-dependent.","title":"Identification of a novel p53 functional domain that is necessary for mediating apoptosis."},{"docid":"4389394","text":"The p53 tumour suppressor is a short-lived protein that is maintained at low levels in normal cells by Mdm2-mediated ubiquitination and subsequent proteolysis. Stabilization of p53 is crucial for its tumour suppressor function. However, the precise mechanism by which ubiquitinated p53 levels are regulated in vivo is not completely understood. By mass spectrometry of affinity-purified p53-associated factors, we have identified herpesvirus-associated ubiquitin-specific protease (HAUSP) as a novel p53-interacting protein. HAUSP strongly stabilizes p53 even in the presence of excess Mdm2, and also induces p53-dependent cell growth repression and apoptosis. Significantly, HAUSP has an intrinsic enzymatic activity that specifically deubiquitinates p53 both in vitro and in vivo. In contrast, expression of a catalytically inactive point mutant of HAUSP in cells increases the levels of p53 ubiquitination and destabilizes p53. These findings reveal an important mechanism by which p53 can be stabilized by direct deubiquitination and also imply that HAUSP might function as a tumour suppressor in vivo through the stabilization of p53.","title":"Deubiquitination of p53 by HAUSP is an important pathway for p53 stabilization"},{"docid":"39637840","text":"BLM, WRN, and p53 are involved in the homologous DNA recombination pathway. The DNA structure-specific helicases, BLM and WRN, unwind Holliday junctions (HJ), an activity that could suppress inappropriate homologous recombination during DNA replication. Here, we show that purified, recombinant p53 binds to BLM and WRN helicases and attenuates their ability to unwind synthetic HJ in vitro. The p53 248W mutant reduces abilities of both to bind HJ and inhibit helicase activities, whereas the p53 273H mutant loses these abilities. Moreover, full-length p53 and a C-terminal polypeptide (residues 373-383) inhibit the BLM and WRN helicase activities, but phosphorylation at Ser(376) or Ser(378) completely abolishes this inhibition. Following blockage of DNA replication, Ser(15) phospho-p53, BLM, and RAD51 colocalize in nuclear foci at sites likely to contain DNA replication intermediates in cells. Our results are consistent with a novel mechanism for p53-mediated regulation of DNA recombinational repair that involves p53 post-translational modifications and functional protein-protein interactions with BLM and WRN DNA helicases.","title":"The processing of Holliday junctions by BLM and WRN helicases is regulated by p53."},{"docid":"25901598","text":"Posttranslational modifications mediate important regulatory functions in biology. The acetylation of the p53 transcription factor, for example, promotes transcriptional activation of target genes including p21. Here we show that the acetylation of two lysine residues in p53 promotes recruitment of the TFIID subunit TAF1 to the p21 promoter through its bromodomains. UV irradiation of cells diacetylates p53 at lysines 373 and 382, which in turn recruits TAF1 to a distal p53-binding site on the p21 promoter prior to looping to the core promoter. Disruption of acetyl-p53/bromodomain interaction inhibits TAF1 recruitment to both the distal p53-binding site and the core promoter. Further, the TFIID subunits TAF4, TAF5, and TBP are detected on the core promoter prior to TAF1, suggesting that, upon DNA damage, distinct subunits of TFIID may be recruited separately to the p21 promoter and that the transcriptional activation depends on posttranslational modification of the p53 transcription factor.","title":"An acetylation switch in p53 mediates holo-TFIID recruitment."},{"docid":"12240507","text":"Diamond-Blackfan anemia (DBA) is a congenital erythroid hypoplasia caused by haploinsufficiency of genes encoding ribosomal proteins (RPs). Perturbed ribosome biogenesis in DBA has been shown to induce a p53-mediated ribosomal stress response. However, the mechanisms of p53 activation and its relevance for the erythroid defect remain elusive. Previous studies have indicated that activation of p53 is caused by the inhibition of mouse double minute 2 (Mdm2), the main negative regulator of p53, by the 5S ribonucleoprotein particle (RNP). Meanwhile, it is not clear whether this mechanism solely mediates the p53-dependent component found in DBA. To approach this question, we crossed our mouse model for RPS19-deficient DBA with Mdm2C305F knock-in mice that have a disrupted 5S RNP–Mdm2 interaction. Upon induction of the Rps19 deficiency, Mdm2C305F reversed the p53 response and improved expansion of hematopoietic progenitors in vitro, and ameliorated the anemia in vivo. Unexpectedly, disruption of the 5S RNP–Mdm2 interaction also led to selective defect in erythropoiesis. Our findings highlight the sensitivity of erythroid progenitor cells to aberrations in p53 homeostasis mediated by the 5S RNP–Mdm2 interaction. Finally, we provide evidence indicating that physiological activation of the 5S RNP-Mdm2-p53 pathway may contribute to functional decline of the hematopoietic system in a cell-autonomous manner over time.","title":"Disruption of the 5S RNP–Mdm2 interaction significantly improves the erythroid defect in a mouse model for Diamond-Blackfan anemia"},{"docid":"27949347","text":"TP53 is the most frequently mutated gene in human cancer. Functionally, p53 is activated by a host of stress stimuli and, in turn, governs an exquisitely complex anti-proliferative transcriptional program that touches upon a bewildering array of biological responses. Despite the many unveiled facets of the p53 network, a clear appreciation of how and in what contexts p53 exerts its diverse effects remains unclear. How can we interpret p53's disparate activities and the consequences of its dysfunction to understand how cell type, mutation profile, and epigenetic cell state dictate outcomes, and how might we restore its tumor-suppressive activities in cancer?","title":"Putting p53 in Context"},{"docid":"6896063","text":"p53 functions as a transcription factor involved in cell-cycle control, DNA repair, apoptosis and cellular stress responses. However, besides inducing cell growth arrest and apoptosis, p53 activation also modulates cellular senescence and organismal aging. Senescence is an irreversible cell-cycle arrest that has a crucial role both in aging and as a robust physiological antitumor response, which counteracts oncogenic insults. Therefore, via the regulation of senescence, p53 contributes to tumor growth suppression, in a manner strictly dependent by its expression and cellular context. In this review, we focus on the recent advances on the contribution of p53 to cellular senescence and its implication for cancer therapy, and we will discuss p53’s impact on animal lifespan. Moreover, we describe p53-mediated regulation of several physiological pathways that could mediate its role in both senescence and aging.","title":"Senescence and aging: the critical roles of p53"},{"docid":"29367554","text":"BACKGROUND & AIMS Although the p53 tumor suppressor has been extensively studied, many critical questions remain unanswered about the biological functions of p53 homologs, p73 and p63. Accumulating evidence suggests that both p73 and p63 play important roles in regulation of apoptosis, cell differentiation, and therapeutic drug sensitivity. METHODS Gastric epithelial cells were cocultured with Helicobacter pylori, and the roles of p63 and p73 proteins were assessed by luciferase reporter, real-time polymerase chain reaction, immunoblotting, and cell survival assays. Short hairpin RNA and dominant-negative mutants were used to inhibit activity of p73 and p63 isoforms. Human and murine gastric tissues were analyzed by immunohistochemistry with p73 and p63 antibodies and modified Steiner's silver method. RESULTS Interaction of H pylori with gastric epithelial cells leads to robust up-regulation of p73 protein in vitro and in vivo in human gastritis specimens and H pylori-infected mice. The p73 increase resulted in up-regulation of pro-apoptotic genes, NOXA, PUMA, and FAS receptor in gastric epithelial cells. Down-regulation of p73 activity suppressed cell death and Fas receptor induced by H pylori. Bacterial virulence factors within the cag pathogenicity island, c-Abl tyrosine kinase, and interaction with p63 isoforms control the activity of p73. CONCLUSION Our findings implicate p73 in H pylori-induced apoptosis and more generally suggest that the p53 family may play a role in the epithelial cell response to H pylori infection.","title":"Interaction of Helicobacter pylori with gastric epithelial cells is mediated by the p53 protein family."},{"docid":"28107602","text":"The oncogene MDMX is overexpressed in many cancers, leading to suppression of the tumor suppressor p53. Inhibitors of the oncogene product MDMX therefore might help reactivate p53 and enhance the efficacy of DNA-damaging drugs. However, we currently lack a quantitative understanding of how MDMX inhibition affects the p53 signaling pathway and cell sensitivity to DNA damage. Live cell imaging showed that MDMX depletion triggered two distinct phases of p53 accumulation in single cells: an initial postmitotic pulse, followed by low-amplitude oscillations. The response to DNA damage was sharply different in these two phases; in the first phase, MDMX depletion was synergistic with DNA damage in causing cell death, whereas in the second phase, depletion of MDMX inhibited cell death. Thus a quantitative understanding of signal dynamics and cellular states is important for designing an optimal schedule of dual-drug administration.","title":"Schedule-dependent interaction between anticancer treatments"},{"docid":"43880096","text":"Activation of p53 can occur in response to a number of cellular stresses, including DNA damage, hypoxia and nucleotide deprivation. Several forms of DNA damage have been shown to activate p53, including those generated by ionising radiation (IR), radio-mimetic drugs, ultraviolet light (UV) and chemicals such as methyl methane sulfonate (MMS). Under normal conditions, p53 levels are maintained at a low state by virtue of the extremely short-half life of the polypeptide. In addition to this, p53 normally exists in an largely inactive state that is relatively inefficient at binding to DNA and activating transcription. Activation of p53 in response to DNA damage is associated with a rapid increase in its levels and with an increased ability of p53 to bind DNA and mediate transcriptional activation. This then leads to the activation of a number of genes whose products trigger cell-cycle arrest, apoptosis, or DNA repair. Recent work has suggested that this regulation is brought about largely through DNA damage triggering a series of phosphorylation, de-phosphorylation and acetylation events on the p53 polypeptide. Here, we discuss the nature of these modifications, the enzymes that bring them about, and how changes in p53 modification lead to p53 activation.","title":"Regulation of p53 in response to DNA damage"},{"docid":"42489926","text":"p53 regulates a key pathway which protects normal tissues from tumor development that may result from diverse forms of stress. In the absence of stress, growth suppressive and proapoptotic activity of p53 is inhibited by MDM2 which binds p53 and negatively regulates its activity and stability. MDM2 antagonists could activate p53 and may offer a novel therapeutic approach to cancer. Recently, we identified the first potent and selective low molecular weight inhibitors of MDM2-p53 binding, the Nutlins. These molecules activate the p53 pathway and suppress tumor growth in vitro and in vivo. They represent valuable new tools for studying the p53 pathway and its defects in cancer. Nutlins induce p53-dependent apoptosis in human cancer cells but appear cytostatic to proliferating normal cells. Their potent activity against osteosarcoma xenografts suggests that MDM2 antagonists may have clinical utility in the treatment of tumors with wild-type p53.","title":"Small-molecule antagonists of p53-MDM2 binding: research tools and potential therapeutics."},{"docid":"34103335","text":"A long-standing hypothesis on tumorigenesis is that cell division failure, generating genetically unstable tetraploid cells, facilitates the development of aneuploid malignancies. Here we test this idea by transiently blocking cytokinesis in p53-null (p53-/-) mouse mammary epithelial cells (MMECs), enabling the isolation of diploid and tetraploid cultures. The tetraploid cells had an increase in the frequency of whole-chromosome mis-segregation and chromosomal rearrangements. Only the tetraploid cells were transformed in vitro after exposure to a carcinogen. Furthermore, in the absence of carcinogen, only the tetraploid cells gave rise to malignant mammary epithelial cancers when transplanted subcutaneously into nude mice. These tumours all contained numerous non-reciprocal translocations and an 8–30-fold amplification of a chromosomal region containing a cluster of matrix metalloproteinase (MMP) genes. MMP overexpression is linked to mammary tumours in humans and animal models. Thus, tetraploidy enhances the frequency of chromosomal alterations and promotes tumour development in p53-/- MMECs.","title":"Cytokinesis failure generating tetraploids promotes tumorigenesis in p53-null cells"},{"docid":"47018050","text":"Here, we report that genome editing by CRISPR–Cas9 induces a p53-mediated DNA damage response and cell cycle arrest in immortalized human retinal pigment epithelial cells, leading to a selection against cells with a functional p53 pathway. Inhibition of p53 prevents the damage response and increases the rate of homologous recombination from a donor template. These results suggest that p53 inhibition may improve the efficiency of genome editing of untransformed cells and that p53 function should be monitored when developing cell-based therapies utilizing CRISPR–Cas9. CRISPR–Cas9-induced DNA damage triggers p53 to limit the efficiency of gene editing in immortalized human retinal pigment epithelial cells.","title":"CRISPR–Cas9 genome editing induces a p53-mediated DNA damage response"},{"docid":"25682129","text":"The sequence-specific binding to DNA is crucial for the p53 tumor suppressor function. To investigate the constraints imposed on p53-DNA recognition by nucleosomal organization, we studied binding of the p53 DNA binding domain (p53DBD) and full-length wild-type p53 protein to a single p53 response element (p53RE) placed near the nucleosomal dyad in six rotational settings. We demonstrate that the strongest p53 binding occurs when the p53RE in the nucleosome is bent in the same direction as observed for the p53-DNA complexes in solution and in co-crystals. The p53RE becomes inaccessible, however, if its orientation in the core particle is changed by approximately 180 degrees. Our observations indicate that the orientation of the binding sites on a nucleosome may play a significant role in the initial p53-DNA recognition and subsequent cofactor recruitment.","title":"p53 binding to nucleosomal DNA depends on the rotational positioning of DNA response element."},{"docid":"21295300","text":"The phosphatidylinositol-3-kinase-like kinase ATM (ataxia-telangiectasia mutated) has a central role in coordinating DNA damage responses, including cell-cycle checkpoint control, DNA repair and apoptosis. Mutations of ATM cause a spectrum of defects ranging from neurodegeneration to cancer predisposition. However, the mechanism by which DNA damage activates ATM is poorly understood. Here we show that Cdk5 (cyclin-dependent kinase 5), activated by DNA damage, directly phosphorylates ATM at Ser 794 in post-mitotic neurons. Phosphorylation at Ser 794 precedes, and is required for, ATM autophosphorylation at Ser 1981, and activates ATM kinase activity. The Cdk5-ATM signal regulates phosphorylation and function of the ATM targets p53 and H2AX. Interruption of the Cdk5-ATM pathway attenuates DNA-damage-induced neuronal cell cycle re-entry and expression of the p53 targets PUMA and Bax, protecting neurons from death. Thus, activation of Cdk5 by DNA damage serves as a critical signal to initiate the ATM response and regulate ATM-dependent cellular processes.","title":"Phosphorylation of ATM by Cdk5 mediates DNA damage signaling and regulates neuronal death"},{"docid":"5468807","text":"ARID1A, encoding a subunit of the SWI/SNF chromatin-remodelling complex, is the most frequently mutated epigenetic regulator across all human cancers. ARID1A and TP53 mutations are typically mutually exclusive. Therapeutic approaches that correlate with this genetic characteristic remain to be explored. Here, we show that HDAC6 activity is essential in ARID1A-mutated ovarian cancers. Inhibition of HDAC6 activity using a clinically applicable small-molecule inhibitor significantly improved the survival of mice bearing ARID1A-mutated tumours. This correlated with the suppression of growth and dissemination of ARID1A-mutated, but not wild-type, tumours. The dependence on HDAC6 activity in ARID1A-mutated cells correlated with a direct transcriptional repression of HDAC6 by ARID1A. HDAC6 inhibition selectively promoted apoptosis of ARID1A-mutated cells. HDAC6 directly deacetylates Lys120 of p53, a pro-apoptotic post-translational modification. Thus, ARID1A mutation inactivates the apoptosis-promoting function of p53 by upregulating HDAC6. Together, these results indicate that pharmacological inhibition of HDAC6 is a therapeutic strategy for ARID1A-mutated cancers.","title":"ARID1A-mutated ovarian cancers depend on HDAC6 activity"},{"docid":"21557055","text":"The tumor suppressor protein, p53, plays a critical role in mediating cellular response to stress signals by regulating genes involved in cell cycle arrest and apoptosis. p53 is believed to be inactive for DNA binding unless its C terminus is modified or structurally altered. We show that unmodified p53 actively binds to two sites at -1.4 and -2.3 kb within the chromatin-assembled p21 promoter and requires the C terminus and the histone acetyltransferase, p300, for transcription. Acetylation of the C terminus by p300 is not necessary for binding or promoter activation. Instead, p300 acetylates p53-bound nucleosomes in the p21 promoter with spreading to the TATA box. Thus, p53 is an active DNA and chromatin binding protein that may selectively regulate its target genes by recruitment of specific cofactors to structurally distinct binding sites.","title":"Transcriptional regulation by p53 through intrinsic DNA/chromatin binding and site-directed cofactor recruitment."},{"docid":"9483851","text":"p53 is a crucial tumour suppressor that responds to diverse stress signals by orchestrating specific cellular responses, including transient cell cycle arrest, cellular senescence and apoptosis, which are all processes associated with tumour suppression. However, recent studies have challenged the relative importance of these canonical cellular responses for p53-mediated tumour suppression and have highlighted roles for p53 in modulating other cellular processes, including metabolism, stem cell maintenance, invasion and metastasis, as well as communication within the tumour microenvironment. In this Opinion article, we discuss the roles of classical p53 functions, as well as emerging p53-regulated processes, in tumour suppression.","title":"Unravelling mechanisms of p53-mediated tumour suppression"},{"docid":"26059876","text":"Ku70, a known nonhomologous end-joining (NHEJ) factor, also functions in tumor suppression, although this molecular mechanism remains uncharacterized. Previously, we showed that mice deficient for DNA ligase IV (Lig4), another key NHEJ factor, succumbed to aggressive lymphoma in the absence of tumor suppressor p53. However, the tumor phenotype is abrogated by the introduction of a hypomorphic mutant p53R172P, which impaired p53-mediated apoptosis but not cell-cycle arrest. However, Lig4−/−p53R172P mice succumbed to severe diabetes. To further elucidate the role of NHEJ and p53-mediated apoptosis in vivo, we bred Ku70−/− p53R172P mice. Unexpectedly, these mice were free of diabetes, although 80% of the mutant mice had abnormally enlarged colons with pronounced inflammation. Remarkably, most of these mutant mice progressed to dysplasia, adenoma and adenocarcinoma; this is in contrast to the Lig4−/−p53R172P phenotype, strongly suggesting an NHEJ-independent function of Ku70. Significantly, our analyses of Ku70−/−p53R172P colonic epithelial cells show nuclear stabilization of β-catenin accompanied by higher expression of cyclin D1 and c-Myc in affected colon sections than in control samples. This is not due to the p53 mutation, as Ku70−/− mice share this phenotype. Our results not only unravel a novel function of Ku70 essential for colon homeostasis, but also establish an excellent in vivo model in which to study how chronic inflammation and abnormal cellular proliferation underlie tumorigenesis and tumor progression in the colon.","title":"A novel Ku70 function in colorectal homeostasis separate from nonhomologous end joining"},{"docid":"7465900","text":"BACKGROUND & AIMS Helicobacter pylori-induced gastric epithelial cell (GEC) apoptosis is a complex process that includes activation of the tumor suppressor p53. p53-mediated apoptosis involves p53 activation, bax transcription, and cytochrome c release from mitochondria. Apurinic/apyrimidinic endonuclease-1 (APE-1) regulates transcriptional activity of p53, and H pylori induce APE-1 expression in human GECs. H pylori infection increases intracellular calcium ion concentration [Ca2+]i of GECs, which induces APE-1 acetylation. We investigated the effects of H pylori infection and APE-1 acetylation on GEC apoptosis. METHODS AGS cells (wild-type or with suppressed APE-1), KATO III cells, and cells isolated from gastric biopsy specimens were infected with H pylori. Effects were examined by immunoblotting, real-time reverse-transcription polymerase chain reaction, immunoprecipitation, immunofluorescence microscopy, chromatin immunoprecipitation, mobility shift, DNA binding, and luciferase assays. RESULTS H pylori infection increased [Ca2+]i and acetylation of APE-1 in GECs, but the acetylation status of APE-1 did not affect the transcriptional activity of p53. In GECs, expression of a form of APE-1 that could not be acetylated increased total and mitochondrial levels of Bax and induced release of cytochrome c and fragmentation of DNA; expression of wild-type APE-1 reduced these apoptotic events. We identified a negative calcium response element in the human bax promoter and found that poly (adenosine diphosphate-ribose) polymerase 1 recruited the acetylated APE-1/histone deacetylase-1 repressor complex to bax nCaRE. CONCLUSIONS H pylori-mediated acetylation of APE-1 suppresses Bax expression; this prevents p53-mediated apoptosis when H pylori infect GECs.","title":"Acetylation of apurinic/apyrimidinic endonuclease-1 regulates Helicobacter pylori-mediated gastric epithelial cell apoptosis."}],"string":"[\n {\n \"docid\": \"23985464\",\n \"text\": \"Wild-type p53 has recently been shown to repress transcription from several cellular and viral promoters. Since p53 mutations are the most frequently reported genetic defects in human cancers, it becomes important to study the effects of mutations of p53 on promoter functions. We, therefore, have studied the effects of wild-type and mutant human p53 on the human proliferating-cell nuclear antigen (PCNA) promoter and on several viral promoters, including the herpes simplex virus type 1 UL9 promoter, the human cytomegalovirus major immediate-early promoter-enhancer, and the long terminal repeat promoters of Rous sarcoma virus and human T-cell lymphotropic virus type I. HeLa cells were cotransfected with a wild-type or mutant p53 expression vector and a plasmid containing a chloramphenicol acetyltransferase reporter gene under viral (or cellular) promoter control. As expected, expression of the wild-type p53 inhibited promoter function. Expression of a p53 with a mutation at any one of the four amino acid positions 175, 248, 273, or 281, however, correlated with a significant increase of the PCNA promoter activity (2- to 11-fold). The viral promoters were also activated, although to a somewhat lesser extent. We also showed that activation by a mutant p53 requires a minimal promoter containing a lone TATA box. A more significant increase (25-fold) in activation occurs when the promoter contains a binding site for the activating transcription factor or cyclic AMP response element-binding protein. Using Saos-2 cells that do not express p53, we showed that activation by a mutant p53 was a direct enhancement. The mutant forms of p53 used in this study are found in various cancer cells. The activation of PCNA by mutant p53s may indicate a way to increase cell proliferation by the mutant p53s. Thus, our data indicate a possible functional role for the mutants of p53 found in cancer cells in activating several important loci, including PCNA.\",\n \"title\": \"Modulation of cellular and viral promoters by mutant human p53 proteins found in tumor cells.\"\n },\n {\n \"docid\": \"21307488\",\n \"text\": \"HER-2/neu amplification or overexpression can make cancer cells resistant to apoptosis and promotes their growth. p53 is crucial in regulating cell growth and apoptosis, and is often mutated or deleted in many types of tumour. Moreover, many tumours with a wild-type gene for p53 do not have normal p53 function, suggesting that some oncogenic signals suppress the function of p53. In this study, we show that HER-2/neu-mediated resistance to DNA-damaging agents requires the activation of Akt, which enhances MDM2-mediated ubiquitination and degradation of p53. Akt physically associates with MDM2 and phosphorylates it at Ser166 and Ser186. Phosphorylation of MDM2 enhances its nuclear localization and its interaction with p300, and inhibits its interaction with p19ARF, thus increasing p53 degradation. Our study indicates that blocking the Akt pathway mediated by HER-2/neu would increase the cytotoxic effect of DNA-damaging drugs in tumour cells with wild-type p53.\",\n \"title\": \"HER-2/neu induces p53 ubiquitination via Akt-mediated MDM2 phosphorylation\"\n },\n {\n \"docid\": \"9669099\",\n \"text\": \"Binding within or nearby target genes involved in cell proliferation and survival enables the p53 tumor suppressor gene to regulate their transcription and cell-cycle progression. Using genome-wide chromatin-binding profiles, we describe binding of p53 also to regions located distantly from any known p53 target gene. Interestingly, many of these regions possess conserved p53-binding sites and all known hallmarks of enhancer regions. We demonstrate that these p53-bound enhancer regions (p53BERs) indeed contain enhancer activity and interact intrachromosomally with multiple neighboring genes to convey long-distance p53-dependent transcription regulation. Furthermore, p53BERs produce, in a p53-dependent manner, enhancer RNAs (eRNAs) that are required for efficient transcriptional enhancement of interacting target genes and induction of a p53-dependent cell-cycle arrest. Thus, our results ascribe transcription enhancement activity to p53 with the capacity to regulate multiple genes from a single genomic binding site. Moreover, eRNA production from p53BERs is required for efficient p53 transcription enhancement.\",\n \"title\": \"eRNAs are required for p53-dependent enhancer activity and gene transcription.\"\n },\n {\n \"docid\": \"37204802\",\n \"text\": \"Jumonji domain-containing 6 (JMJD6) is a member of the Jumonji C domain-containing family of proteins. Compared to other members of the family, the cellular activity of JMJD6 is still not clearly defined and its biological function is still largely unexplored. Here we report that JMJD6 is physically associated with the tumor suppressor p53. We demonstrated that JMJD6 acts as an α-ketoglutarate- and Fe(II)-dependent lysyl hydroxylase to catalyze p53 hydroxylation. We found that p53 indeed exists as a hydroxylated protein in vivo and that the hydroxylation occurs mainly on lysine 382 of p53. We showed that JMJD6 antagonizes p53 acetylation, promotes the association of p53 with its negative regulator MDMX, and represses transcriptional activity of p53. Depletion of JMJD6 enhances p53 transcriptional activity, arrests cells in the G1 phase, promotes cell apoptosis, and sensitizes cells to DNA damaging agent-induced cell death. Importantly, knockdown of JMJD6 represses p53-dependent colon cell proliferation and tumorigenesis in vivo, and significantly, the expression of JMJD6 is markedly up-regulated in various types of human cancer especially in colon cancer, and high nuclear JMJD6 protein is strongly correlated with aggressive clinical behaviors of colon adenocarcinomas. Our results reveal a novel posttranslational modification for p53 and support the pursuit of JMJD6 as a potential biomarker for colon cancer aggressiveness and a potential target for colon cancer intervention.\",\n \"title\": \"JMJD6 Promotes Colon Carcinogenesis through Negative Regulation of p53 by Hydroxylation\"\n },\n {\n \"docid\": \"14460402\",\n \"text\": \"The molecular mechanisms that regulate adult neural precursor cell (NPC) survival, and thus maintain adult neurogenesis, are not well defined. Here, we investigate the role of p63, a p53 family member, in adult NPC function in mice. Conditional ablation of p63 in adult NPCs or p63 haploinsufficiency led to reduced numbers of NPCs and newborn neurons in the neurogenic zones of the hippocampus and lateral ventricles and in the olfactory bulb. These reductions were attributable to enhanced apoptosis of NPCs and newborn neurons and were rescued by inhibition of caspase activity, p53, or the p53 apoptotic effector PUMA (p53-upregulated modulator of apoptosis). Moreover, these cellular deficits were functionally important because they led to perturbations in hippocampus-dependent memory formation. These results indicate that p63 regulates the numbers of adult NPCs and adult-born neurons as well as neural stem cell-dependent cognitive functions, and that it does so, at least in part, by inhibiting p53-dependent cell death.\",\n \"title\": \"p63 Regulates adult neural precursor and newly born neuron survival to control hippocampal-dependent Behavior.\"\n },\n {\n \"docid\": \"11903247\",\n \"text\": \"Multiple cellular stressors, including activation of the tumour suppressor p53, can stimulate autophagy. Here we show that deletion, depletion or inhibition of p53 can induce autophagy in human, mouse and nematode cells subjected to knockout, knockdown or pharmacological inhibition of p53. Enhanced autophagy improved the survival of p53-deficient cancer cells under conditions of hypoxia and nutrient depletion, allowing them to maintain high ATP levels. Inhibition of p53 led to autophagy in enucleated cells, and cytoplasmic, not nuclear, p53 was able to repress the enhanced autophagy of p53−/− cells. Many different inducers of autophagy (for example, starvation, rapamycin and toxins affecting the endoplasmic reticulum) stimulated proteasome-mediated degradation of p53 through a pathway relying on the E3 ubiquitin ligase HDM2. Inhibition of p53 degradation prevented the activation of autophagy in several cell lines, in response to several distinct stimuli. These results provide evidence of a key signalling pathway that links autophagy to the cancer-associated dysregulation of p53.\",\n \"title\": \"Regulation of autophagy by cytoplasmic p53\"\n },\n {\n \"docid\": \"4460880\",\n \"text\": \"Endothelial cells contribute to a subset of cardiac fibroblasts by undergoing endothelial-to-mesenchymal transition, but whether cardiac fibroblasts can adopt an endothelial cell fate and directly contribute to neovascularization after cardiac injury is not known. Here, using genetic fate map techniques, we demonstrate that cardiac fibroblasts rapidly adopt an endothelial-cell-like phenotype after acute ischaemic cardiac injury. Fibroblast-derived endothelial cells exhibit anatomical and functional characteristics of native endothelial cells. We show that the transcription factor p53 regulates such a switch in cardiac fibroblast fate. Loss of p53 in cardiac fibroblasts severely decreases the formation of fibroblast-derived endothelial cells, reduces post-infarct vascular density and worsens cardiac function. Conversely, stimulation of the p53 pathway in cardiac fibroblasts augments mesenchymal-to-endothelial transition, enhances vascularity and improves cardiac function. These observations demonstrate that mesenchymal-to-endothelial transition contributes to neovascularization of the injured heart and represents a potential therapeutic target for enhancing cardiac repair.\",\n \"title\": \"Mesenchymal-endothelial-transition contributes to cardiac neovascularization\"\n },\n {\n \"docid\": \"21521236\",\n \"text\": \"In a search for mediators of the p53 tumor suppressor pathway, which induces pleiotropic and often antagonistic cellular responses, we identified the long noncoding RNA (lncRNA) NEAT1. NEAT1 is an essential architectural component of paraspeckle nuclear bodies, whose pathophysiological relevance remains unclear. Activation of p53, pharmacologically or by oncogene-induced replication stress, stimulated the formation of paraspeckles in mouse and human cells. Silencing Neat1 expression in mice, which prevents paraspeckle formation, sensitized preneoplastic cells to DNA-damage-induced cell death and impaired skin tumorigenesis. We provide mechanistic evidence that NEAT1 promotes ATR signaling in response to replication stress and is thereby engaged in a negative feedback loop that attenuates oncogene-dependent activation of p53. NEAT1 targeting in established human cancer cell lines induced synthetic lethality with genotoxic chemotherapeutics, including PARP inhibitors, and nongenotoxic activation of p53. This study establishes a key genetic link between NEAT1 paraspeckles, p53 biology and tumorigenesis and identifies NEAT1 as a promising target to enhance sensitivity of cancer cells to both chemotherapy and p53 reactivation therapy.\",\n \"title\": \"p53 induces formation of NEAT1 lncRNA-containing paraspeckles that modulate replication stress response and chemosensitivity\"\n },\n {\n \"docid\": \"10015292\",\n \"text\": \"Highly regenerative tissues such as blood must possess effective DNA damage responses (DDR) that balance long-term regeneration with protection from leukemogenesis. Hematopoietic stem cells (HSCs) sustain life-long blood production, yet their response to DNA damage remains largely unexplored. We report that human HSCs exhibit delayed DNA double-strand break rejoining, persistent gammaH2AX foci, and enhanced p53- and ASPP1-dependent apoptosis after gamma-radiation compared to progenitors. p53 inactivation or Bcl-2 overexpression reduced radiation-induced apoptosis and preserved in vivo repopulating HSC function. Despite similar protection from irradiation-induced apoptosis, only Bcl-2-overexpressing HSCs showed higher self-renewal capacity, establishing that intact p53 positively regulates self-renewal independently from apoptosis. The reduced self-renewal of HSCs with inactivated p53 was associated with increased spontaneous gammaH2AX foci in secondary transplants of HSCs. Our data reveal distinct physiological roles of p53 that together ensure optimal HSC function: apoptosis regulation and prevention of gammaH2AX foci accumulation upon HSC self-renewal.\",\n \"title\": \"A distinctive DNA damage response in human hematopoietic stem cells reveals an apoptosis-independent role for p53 in self-renewal.\"\n },\n {\n \"docid\": \"35684881\",\n \"text\": \"Tumor-derived p53 mutants can transcriptionally activate a number of promoters of genes involved in cellular proliferation. For this transactivation, mutant p53 does not use the wild-type p53 DNA-binding site, suggesting a mechanism of transactivation that is independent of direct DNA binding. Here we describe our analysis of the domain requirements for mutant p53 to transactivate promoters of the human epidermal growth factor receptor (EGFR), human multiple drug resistance 1 (MDR-1) and human proliferating cell nuclear antigen (PCNA) genes. We also report the identification of a structural domain required for the `gain of function' property of mutant p53-281G. `Gain of function' is measured as the tumorigenicity (in nude mice) of 10(3) murine cells expressing mutant p53 constitutively. We have generated internal deletion mutants of p53-281G deleting conserved domains I, II, III, IV and V, individually. We have also generated one deletion mutant eliminating amino acids 100 through 300 that removes four of the five conserved domains (II–V); another mutant, p53-281G del 393-327, deletes the oligomerization and nonsequence-specific nucleic acid-binding domains of p53. For the EGFR and MDR-1 promoters, all these mutants have significantly lower transactivation ability than intact p53-281G. These deletion mutants, however, significantly activated the pCNA promoter, suggesting that the mechanism of transactivation of the PCNA promoter is different from that of the EGFR and MDR-1 promoters. When expressed constitutively in 10(3) cells, p53-281G del 393-327 was found to be defective in inducing tumor formation in nude mice although intact p53-281G was very efficient. Thus, our results suggest that structural domains near the C-terminus are needed for `gain of function'.\",\n \"title\": \"`Gain of function' phenotype of tumor-derived mutant p53 requires the oligomerization/nonsequence-specific nucleic acid-binding domain\"\n },\n {\n \"docid\": \"9169645\",\n \"text\": \"The ability of p53 to induce apoptosis requires its sequence-specific DNA binding activity; however, the transactivation-deficient p53(Gln22-Ser23) can still induce apoptosis. Previously, we have shown that the region between residues 23 and 97 in p53 is necessary for such activity. In an effort to more precisely map a domain necessary for apoptosis within the N terminus, we found that deletion of the N-terminal 23 amino acids compromises, but does not abolish, p53 induction of apoptosis. Surprisingly, p53(Delta1-42), which lacks the N-terminal 42 amino acids and the previously defined activation domain, retains the ability to induce apoptosis to an even higher level than wild-type p53. A more extensive deletion, which eliminates the N-terminal 63 amino acids, renders p53 completely inert in mediating apoptosis. In addition, we found that both p53(Delta1-42) and p53(Gln22-Ser23) can activate a subset of cellular p53 targets. Furthermore, we showed that residues 53 and 54 are critical for the apoptotic and transcriptional activities of both p53(Delta1-42) and p53(Gln22-Ser23). Taken together, these data suggest that within residues 43-63 lie an apoptotic domain as well as another transcriptional activation domain. We therefore postulate that the apoptotic activity in p53(Gln22-Ser23) and p53(Delta1-42) is still transcription-dependent.\",\n \"title\": \"Identification of a novel p53 functional domain that is necessary for mediating apoptosis.\"\n },\n {\n \"docid\": \"4389394\",\n \"text\": \"The p53 tumour suppressor is a short-lived protein that is maintained at low levels in normal cells by Mdm2-mediated ubiquitination and subsequent proteolysis. Stabilization of p53 is crucial for its tumour suppressor function. However, the precise mechanism by which ubiquitinated p53 levels are regulated in vivo is not completely understood. By mass spectrometry of affinity-purified p53-associated factors, we have identified herpesvirus-associated ubiquitin-specific protease (HAUSP) as a novel p53-interacting protein. HAUSP strongly stabilizes p53 even in the presence of excess Mdm2, and also induces p53-dependent cell growth repression and apoptosis. Significantly, HAUSP has an intrinsic enzymatic activity that specifically deubiquitinates p53 both in vitro and in vivo. In contrast, expression of a catalytically inactive point mutant of HAUSP in cells increases the levels of p53 ubiquitination and destabilizes p53. These findings reveal an important mechanism by which p53 can be stabilized by direct deubiquitination and also imply that HAUSP might function as a tumour suppressor in vivo through the stabilization of p53.\",\n \"title\": \"Deubiquitination of p53 by HAUSP is an important pathway for p53 stabilization\"\n },\n {\n \"docid\": \"39637840\",\n \"text\": \"BLM, WRN, and p53 are involved in the homologous DNA recombination pathway. The DNA structure-specific helicases, BLM and WRN, unwind Holliday junctions (HJ), an activity that could suppress inappropriate homologous recombination during DNA replication. Here, we show that purified, recombinant p53 binds to BLM and WRN helicases and attenuates their ability to unwind synthetic HJ in vitro. The p53 248W mutant reduces abilities of both to bind HJ and inhibit helicase activities, whereas the p53 273H mutant loses these abilities. Moreover, full-length p53 and a C-terminal polypeptide (residues 373-383) inhibit the BLM and WRN helicase activities, but phosphorylation at Ser(376) or Ser(378) completely abolishes this inhibition. Following blockage of DNA replication, Ser(15) phospho-p53, BLM, and RAD51 colocalize in nuclear foci at sites likely to contain DNA replication intermediates in cells. Our results are consistent with a novel mechanism for p53-mediated regulation of DNA recombinational repair that involves p53 post-translational modifications and functional protein-protein interactions with BLM and WRN DNA helicases.\",\n \"title\": \"The processing of Holliday junctions by BLM and WRN helicases is regulated by p53.\"\n },\n {\n \"docid\": \"25901598\",\n \"text\": \"Posttranslational modifications mediate important regulatory functions in biology. The acetylation of the p53 transcription factor, for example, promotes transcriptional activation of target genes including p21. Here we show that the acetylation of two lysine residues in p53 promotes recruitment of the TFIID subunit TAF1 to the p21 promoter through its bromodomains. UV irradiation of cells diacetylates p53 at lysines 373 and 382, which in turn recruits TAF1 to a distal p53-binding site on the p21 promoter prior to looping to the core promoter. Disruption of acetyl-p53/bromodomain interaction inhibits TAF1 recruitment to both the distal p53-binding site and the core promoter. Further, the TFIID subunits TAF4, TAF5, and TBP are detected on the core promoter prior to TAF1, suggesting that, upon DNA damage, distinct subunits of TFIID may be recruited separately to the p21 promoter and that the transcriptional activation depends on posttranslational modification of the p53 transcription factor.\",\n \"title\": \"An acetylation switch in p53 mediates holo-TFIID recruitment.\"\n },\n {\n \"docid\": \"12240507\",\n \"text\": \"Diamond-Blackfan anemia (DBA) is a congenital erythroid hypoplasia caused by haploinsufficiency of genes encoding ribosomal proteins (RPs). Perturbed ribosome biogenesis in DBA has been shown to induce a p53-mediated ribosomal stress response. However, the mechanisms of p53 activation and its relevance for the erythroid defect remain elusive. Previous studies have indicated that activation of p53 is caused by the inhibition of mouse double minute 2 (Mdm2), the main negative regulator of p53, by the 5S ribonucleoprotein particle (RNP). Meanwhile, it is not clear whether this mechanism solely mediates the p53-dependent component found in DBA. To approach this question, we crossed our mouse model for RPS19-deficient DBA with Mdm2C305F knock-in mice that have a disrupted 5S RNP–Mdm2 interaction. Upon induction of the Rps19 deficiency, Mdm2C305F reversed the p53 response and improved expansion of hematopoietic progenitors in vitro, and ameliorated the anemia in vivo. Unexpectedly, disruption of the 5S RNP–Mdm2 interaction also led to selective defect in erythropoiesis. Our findings highlight the sensitivity of erythroid progenitor cells to aberrations in p53 homeostasis mediated by the 5S RNP–Mdm2 interaction. Finally, we provide evidence indicating that physiological activation of the 5S RNP-Mdm2-p53 pathway may contribute to functional decline of the hematopoietic system in a cell-autonomous manner over time.\",\n \"title\": \"Disruption of the 5S RNP–Mdm2 interaction significantly improves the erythroid defect in a mouse model for Diamond-Blackfan anemia\"\n },\n {\n \"docid\": \"27949347\",\n \"text\": \"TP53 is the most frequently mutated gene in human cancer. Functionally, p53 is activated by a host of stress stimuli and, in turn, governs an exquisitely complex anti-proliferative transcriptional program that touches upon a bewildering array of biological responses. Despite the many unveiled facets of the p53 network, a clear appreciation of how and in what contexts p53 exerts its diverse effects remains unclear. How can we interpret p53's disparate activities and the consequences of its dysfunction to understand how cell type, mutation profile, and epigenetic cell state dictate outcomes, and how might we restore its tumor-suppressive activities in cancer?\",\n \"title\": \"Putting p53 in Context\"\n },\n {\n \"docid\": \"6896063\",\n \"text\": \"p53 functions as a transcription factor involved in cell-cycle control, DNA repair, apoptosis and cellular stress responses. However, besides inducing cell growth arrest and apoptosis, p53 activation also modulates cellular senescence and organismal aging. Senescence is an irreversible cell-cycle arrest that has a crucial role both in aging and as a robust physiological antitumor response, which counteracts oncogenic insults. Therefore, via the regulation of senescence, p53 contributes to tumor growth suppression, in a manner strictly dependent by its expression and cellular context. In this review, we focus on the recent advances on the contribution of p53 to cellular senescence and its implication for cancer therapy, and we will discuss p53’s impact on animal lifespan. Moreover, we describe p53-mediated regulation of several physiological pathways that could mediate its role in both senescence and aging.\",\n \"title\": \"Senescence and aging: the critical roles of p53\"\n },\n {\n \"docid\": \"29367554\",\n \"text\": \"BACKGROUND & AIMS Although the p53 tumor suppressor has been extensively studied, many critical questions remain unanswered about the biological functions of p53 homologs, p73 and p63. Accumulating evidence suggests that both p73 and p63 play important roles in regulation of apoptosis, cell differentiation, and therapeutic drug sensitivity. METHODS Gastric epithelial cells were cocultured with Helicobacter pylori, and the roles of p63 and p73 proteins were assessed by luciferase reporter, real-time polymerase chain reaction, immunoblotting, and cell survival assays. Short hairpin RNA and dominant-negative mutants were used to inhibit activity of p73 and p63 isoforms. Human and murine gastric tissues were analyzed by immunohistochemistry with p73 and p63 antibodies and modified Steiner's silver method. RESULTS Interaction of H pylori with gastric epithelial cells leads to robust up-regulation of p73 protein in vitro and in vivo in human gastritis specimens and H pylori-infected mice. The p73 increase resulted in up-regulation of pro-apoptotic genes, NOXA, PUMA, and FAS receptor in gastric epithelial cells. Down-regulation of p73 activity suppressed cell death and Fas receptor induced by H pylori. Bacterial virulence factors within the cag pathogenicity island, c-Abl tyrosine kinase, and interaction with p63 isoforms control the activity of p73. CONCLUSION Our findings implicate p73 in H pylori-induced apoptosis and more generally suggest that the p53 family may play a role in the epithelial cell response to H pylori infection.\",\n \"title\": \"Interaction of Helicobacter pylori with gastric epithelial cells is mediated by the p53 protein family.\"\n },\n {\n \"docid\": \"28107602\",\n \"text\": \"The oncogene MDMX is overexpressed in many cancers, leading to suppression of the tumor suppressor p53. Inhibitors of the oncogene product MDMX therefore might help reactivate p53 and enhance the efficacy of DNA-damaging drugs. However, we currently lack a quantitative understanding of how MDMX inhibition affects the p53 signaling pathway and cell sensitivity to DNA damage. Live cell imaging showed that MDMX depletion triggered two distinct phases of p53 accumulation in single cells: an initial postmitotic pulse, followed by low-amplitude oscillations. The response to DNA damage was sharply different in these two phases; in the first phase, MDMX depletion was synergistic with DNA damage in causing cell death, whereas in the second phase, depletion of MDMX inhibited cell death. Thus a quantitative understanding of signal dynamics and cellular states is important for designing an optimal schedule of dual-drug administration.\",\n \"title\": \"Schedule-dependent interaction between anticancer treatments\"\n },\n {\n \"docid\": \"43880096\",\n \"text\": \"Activation of p53 can occur in response to a number of cellular stresses, including DNA damage, hypoxia and nucleotide deprivation. Several forms of DNA damage have been shown to activate p53, including those generated by ionising radiation (IR), radio-mimetic drugs, ultraviolet light (UV) and chemicals such as methyl methane sulfonate (MMS). Under normal conditions, p53 levels are maintained at a low state by virtue of the extremely short-half life of the polypeptide. In addition to this, p53 normally exists in an largely inactive state that is relatively inefficient at binding to DNA and activating transcription. Activation of p53 in response to DNA damage is associated with a rapid increase in its levels and with an increased ability of p53 to bind DNA and mediate transcriptional activation. This then leads to the activation of a number of genes whose products trigger cell-cycle arrest, apoptosis, or DNA repair. Recent work has suggested that this regulation is brought about largely through DNA damage triggering a series of phosphorylation, de-phosphorylation and acetylation events on the p53 polypeptide. Here, we discuss the nature of these modifications, the enzymes that bring them about, and how changes in p53 modification lead to p53 activation.\",\n \"title\": \"Regulation of p53 in response to DNA damage\"\n },\n {\n \"docid\": \"42489926\",\n \"text\": \"p53 regulates a key pathway which protects normal tissues from tumor development that may result from diverse forms of stress. In the absence of stress, growth suppressive and proapoptotic activity of p53 is inhibited by MDM2 which binds p53 and negatively regulates its activity and stability. MDM2 antagonists could activate p53 and may offer a novel therapeutic approach to cancer. Recently, we identified the first potent and selective low molecular weight inhibitors of MDM2-p53 binding, the Nutlins. These molecules activate the p53 pathway and suppress tumor growth in vitro and in vivo. They represent valuable new tools for studying the p53 pathway and its defects in cancer. Nutlins induce p53-dependent apoptosis in human cancer cells but appear cytostatic to proliferating normal cells. Their potent activity against osteosarcoma xenografts suggests that MDM2 antagonists may have clinical utility in the treatment of tumors with wild-type p53.\",\n \"title\": \"Small-molecule antagonists of p53-MDM2 binding: research tools and potential therapeutics.\"\n },\n {\n \"docid\": \"34103335\",\n \"text\": \"A long-standing hypothesis on tumorigenesis is that cell division failure, generating genetically unstable tetraploid cells, facilitates the development of aneuploid malignancies. Here we test this idea by transiently blocking cytokinesis in p53-null (p53-/-) mouse mammary epithelial cells (MMECs), enabling the isolation of diploid and tetraploid cultures. The tetraploid cells had an increase in the frequency of whole-chromosome mis-segregation and chromosomal rearrangements. Only the tetraploid cells were transformed in vitro after exposure to a carcinogen. Furthermore, in the absence of carcinogen, only the tetraploid cells gave rise to malignant mammary epithelial cancers when transplanted subcutaneously into nude mice. These tumours all contained numerous non-reciprocal translocations and an 8–30-fold amplification of a chromosomal region containing a cluster of matrix metalloproteinase (MMP) genes. MMP overexpression is linked to mammary tumours in humans and animal models. Thus, tetraploidy enhances the frequency of chromosomal alterations and promotes tumour development in p53-/- MMECs.\",\n \"title\": \"Cytokinesis failure generating tetraploids promotes tumorigenesis in p53-null cells\"\n },\n {\n \"docid\": \"47018050\",\n \"text\": \"Here, we report that genome editing by CRISPR–Cas9 induces a p53-mediated DNA damage response and cell cycle arrest in immortalized human retinal pigment epithelial cells, leading to a selection against cells with a functional p53 pathway. Inhibition of p53 prevents the damage response and increases the rate of homologous recombination from a donor template. These results suggest that p53 inhibition may improve the efficiency of genome editing of untransformed cells and that p53 function should be monitored when developing cell-based therapies utilizing CRISPR–Cas9. CRISPR–Cas9-induced DNA damage triggers p53 to limit the efficiency of gene editing in immortalized human retinal pigment epithelial cells.\",\n \"title\": \"CRISPR–Cas9 genome editing induces a p53-mediated DNA damage response\"\n },\n {\n \"docid\": \"25682129\",\n \"text\": \"The sequence-specific binding to DNA is crucial for the p53 tumor suppressor function. To investigate the constraints imposed on p53-DNA recognition by nucleosomal organization, we studied binding of the p53 DNA binding domain (p53DBD) and full-length wild-type p53 protein to a single p53 response element (p53RE) placed near the nucleosomal dyad in six rotational settings. We demonstrate that the strongest p53 binding occurs when the p53RE in the nucleosome is bent in the same direction as observed for the p53-DNA complexes in solution and in co-crystals. The p53RE becomes inaccessible, however, if its orientation in the core particle is changed by approximately 180 degrees. Our observations indicate that the orientation of the binding sites on a nucleosome may play a significant role in the initial p53-DNA recognition and subsequent cofactor recruitment.\",\n \"title\": \"p53 binding to nucleosomal DNA depends on the rotational positioning of DNA response element.\"\n },\n {\n \"docid\": \"21295300\",\n \"text\": \"The phosphatidylinositol-3-kinase-like kinase ATM (ataxia-telangiectasia mutated) has a central role in coordinating DNA damage responses, including cell-cycle checkpoint control, DNA repair and apoptosis. Mutations of ATM cause a spectrum of defects ranging from neurodegeneration to cancer predisposition. However, the mechanism by which DNA damage activates ATM is poorly understood. Here we show that Cdk5 (cyclin-dependent kinase 5), activated by DNA damage, directly phosphorylates ATM at Ser 794 in post-mitotic neurons. Phosphorylation at Ser 794 precedes, and is required for, ATM autophosphorylation at Ser 1981, and activates ATM kinase activity. The Cdk5-ATM signal regulates phosphorylation and function of the ATM targets p53 and H2AX. Interruption of the Cdk5-ATM pathway attenuates DNA-damage-induced neuronal cell cycle re-entry and expression of the p53 targets PUMA and Bax, protecting neurons from death. Thus, activation of Cdk5 by DNA damage serves as a critical signal to initiate the ATM response and regulate ATM-dependent cellular processes.\",\n \"title\": \"Phosphorylation of ATM by Cdk5 mediates DNA damage signaling and regulates neuronal death\"\n },\n {\n \"docid\": \"5468807\",\n \"text\": \"ARID1A, encoding a subunit of the SWI/SNF chromatin-remodelling complex, is the most frequently mutated epigenetic regulator across all human cancers. ARID1A and TP53 mutations are typically mutually exclusive. Therapeutic approaches that correlate with this genetic characteristic remain to be explored. Here, we show that HDAC6 activity is essential in ARID1A-mutated ovarian cancers. Inhibition of HDAC6 activity using a clinically applicable small-molecule inhibitor significantly improved the survival of mice bearing ARID1A-mutated tumours. This correlated with the suppression of growth and dissemination of ARID1A-mutated, but not wild-type, tumours. The dependence on HDAC6 activity in ARID1A-mutated cells correlated with a direct transcriptional repression of HDAC6 by ARID1A. HDAC6 inhibition selectively promoted apoptosis of ARID1A-mutated cells. HDAC6 directly deacetylates Lys120 of p53, a pro-apoptotic post-translational modification. Thus, ARID1A mutation inactivates the apoptosis-promoting function of p53 by upregulating HDAC6. Together, these results indicate that pharmacological inhibition of HDAC6 is a therapeutic strategy for ARID1A-mutated cancers.\",\n \"title\": \"ARID1A-mutated ovarian cancers depend on HDAC6 activity\"\n },\n {\n \"docid\": \"21557055\",\n \"text\": \"The tumor suppressor protein, p53, plays a critical role in mediating cellular response to stress signals by regulating genes involved in cell cycle arrest and apoptosis. p53 is believed to be inactive for DNA binding unless its C terminus is modified or structurally altered. We show that unmodified p53 actively binds to two sites at -1.4 and -2.3 kb within the chromatin-assembled p21 promoter and requires the C terminus and the histone acetyltransferase, p300, for transcription. Acetylation of the C terminus by p300 is not necessary for binding or promoter activation. Instead, p300 acetylates p53-bound nucleosomes in the p21 promoter with spreading to the TATA box. Thus, p53 is an active DNA and chromatin binding protein that may selectively regulate its target genes by recruitment of specific cofactors to structurally distinct binding sites.\",\n \"title\": \"Transcriptional regulation by p53 through intrinsic DNA/chromatin binding and site-directed cofactor recruitment.\"\n },\n {\n \"docid\": \"9483851\",\n \"text\": \"p53 is a crucial tumour suppressor that responds to diverse stress signals by orchestrating specific cellular responses, including transient cell cycle arrest, cellular senescence and apoptosis, which are all processes associated with tumour suppression. However, recent studies have challenged the relative importance of these canonical cellular responses for p53-mediated tumour suppression and have highlighted roles for p53 in modulating other cellular processes, including metabolism, stem cell maintenance, invasion and metastasis, as well as communication within the tumour microenvironment. In this Opinion article, we discuss the roles of classical p53 functions, as well as emerging p53-regulated processes, in tumour suppression.\",\n \"title\": \"Unravelling mechanisms of p53-mediated tumour suppression\"\n },\n {\n \"docid\": \"26059876\",\n \"text\": \"Ku70, a known nonhomologous end-joining (NHEJ) factor, also functions in tumor suppression, although this molecular mechanism remains uncharacterized. Previously, we showed that mice deficient for DNA ligase IV (Lig4), another key NHEJ factor, succumbed to aggressive lymphoma in the absence of tumor suppressor p53. However, the tumor phenotype is abrogated by the introduction of a hypomorphic mutant p53R172P, which impaired p53-mediated apoptosis but not cell-cycle arrest. However, Lig4−/−p53R172P mice succumbed to severe diabetes. To further elucidate the role of NHEJ and p53-mediated apoptosis in vivo, we bred Ku70−/− p53R172P mice. Unexpectedly, these mice were free of diabetes, although 80% of the mutant mice had abnormally enlarged colons with pronounced inflammation. Remarkably, most of these mutant mice progressed to dysplasia, adenoma and adenocarcinoma; this is in contrast to the Lig4−/−p53R172P phenotype, strongly suggesting an NHEJ-independent function of Ku70. Significantly, our analyses of Ku70−/−p53R172P colonic epithelial cells show nuclear stabilization of β-catenin accompanied by higher expression of cyclin D1 and c-Myc in affected colon sections than in control samples. This is not due to the p53 mutation, as Ku70−/− mice share this phenotype. Our results not only unravel a novel function of Ku70 essential for colon homeostasis, but also establish an excellent in vivo model in which to study how chronic inflammation and abnormal cellular proliferation underlie tumorigenesis and tumor progression in the colon.\",\n \"title\": \"A novel Ku70 function in colorectal homeostasis separate from nonhomologous end joining\"\n },\n {\n \"docid\": \"7465900\",\n \"text\": \"BACKGROUND & AIMS Helicobacter pylori-induced gastric epithelial cell (GEC) apoptosis is a complex process that includes activation of the tumor suppressor p53. p53-mediated apoptosis involves p53 activation, bax transcription, and cytochrome c release from mitochondria. Apurinic/apyrimidinic endonuclease-1 (APE-1) regulates transcriptional activity of p53, and H pylori induce APE-1 expression in human GECs. H pylori infection increases intracellular calcium ion concentration [Ca2+]i of GECs, which induces APE-1 acetylation. We investigated the effects of H pylori infection and APE-1 acetylation on GEC apoptosis. METHODS AGS cells (wild-type or with suppressed APE-1), KATO III cells, and cells isolated from gastric biopsy specimens were infected with H pylori. Effects were examined by immunoblotting, real-time reverse-transcription polymerase chain reaction, immunoprecipitation, immunofluorescence microscopy, chromatin immunoprecipitation, mobility shift, DNA binding, and luciferase assays. RESULTS H pylori infection increased [Ca2+]i and acetylation of APE-1 in GECs, but the acetylation status of APE-1 did not affect the transcriptional activity of p53. In GECs, expression of a form of APE-1 that could not be acetylated increased total and mitochondrial levels of Bax and induced release of cytochrome c and fragmentation of DNA; expression of wild-type APE-1 reduced these apoptotic events. We identified a negative calcium response element in the human bax promoter and found that poly (adenosine diphosphate-ribose) polymerase 1 recruited the acetylated APE-1/histone deacetylase-1 repressor complex to bax nCaRE. CONCLUSIONS H pylori-mediated acetylation of APE-1 suppresses Bax expression; this prevents p53-mediated apoptosis when H pylori infect GECs.\",\n \"title\": \"Acetylation of apurinic/apyrimidinic endonuclease-1 regulates Helicobacter pylori-mediated gastric epithelial cell apoptosis.\"\n }\n]"}}},{"rowIdx":194,"cells":{"query_id":{"kind":"string","value":"5497"},"query":{"kind":"string","value":"What kinds of exchange-traded funds (ETFs) should specifically be avoided?"},"positive_passages":{"kind":"list like","value":[{"docid":"210257","text":"\"As with ANY investment the first answer is....do not invest in any that you do not fully understand. ETF's are very versatile and can be used for many different people for many different parts of their portfolio, so I don't think there can be a blanket statement of \"\"this\"\" one is good or bad for all.\"","title":""},{"docid":"86627","text":"\"Stay away from leveraged or synthetic ETFs. This answer talks about why leveraged ETFs are dangerous. There are numerous articles to be found by searching for \"\"leveraged etf\"\". My answer to this question links to one of the more accessible explanations I've read.\"","title":""},{"docid":"324697","text":"One of the key things to look for is trading volume. I think the price spread will be better on high volume ETFs, which means you'll be able to sell for more when the time comes. Check Google or Yahoo finance for those stats.","title":""}],"string":"[\n {\n \"docid\": \"210257\",\n \"text\": \"\\\"As with ANY investment the first answer is....do not invest in any that you do not fully understand. ETF's are very versatile and can be used for many different people for many different parts of their portfolio, so I don't think there can be a blanket statement of \\\"\\\"this\\\"\\\" one is good or bad for all.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"86627\",\n \"text\": \"\\\"Stay away from leveraged or synthetic ETFs. This answer talks about why leveraged ETFs are dangerous. There are numerous articles to be found by searching for \\\"\\\"leveraged etf\\\"\\\". My answer to this question links to one of the more accessible explanations I've read.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"324697\",\n \"text\": \"One of the key things to look for is trading volume. I think the price spread will be better on high volume ETFs, which means you'll be able to sell for more when the time comes. Check Google or Yahoo finance for those stats.\",\n \"title\": \"\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"332924","text":"\"I recommend avoiding trading directly in commodities futures and options. If you're not prepared to learn a lot about how futures markets and trading works, it will be an experience fraught with pitfalls and lost money – and I am speaking from experience. Looking at stock-exchange listed products is a reasonable approach for an individual investor desiring added diversification for their portfolio. Still, exercise caution and know what you're buying. It's easy to access many commodity-based exchange-traded funds (ETFs) on North American stock exchanges. If you already have low-cost access to U.S. markets, consider this option – but be mindful of currency conversion costs, etc. Yet, there is also a European-based company, ETF Securities, headquartered in Jersey, Channel Islands, which offers many exchange-traded funds on European exchanges such as London and Frankfurt. ETF Securities started in 2003 by first offering a gold commodity exchange-traded fund. I also found the following: London Stock Exchange: Frequently Asked Questions about ETCs. The LSE ETC FAQ specifically mentions \"\"ETF Securities\"\" by name, and addresses questions such as how/where they are regulated, what happens to investments if \"\"ETF Securities\"\" were to go bankrupt, etc. I hope this helps, but please, do your own due diligence.\"","title":""},{"docid":"161201","text":"Your assumption that funds sold in GBP trade in GBP is incorrect. In general funds purchase their constituent stocks in the fund currency which may be different to the subscription currency. Where the subscription currency is different from the fund currency subscriptions are converted into the fund currency before the extra money is used to increase holdings. An ETF, on the other hand, does not take subscriptions directly but by creation (and redemption) of shares. The principle is the same however; monies received from creation of ETF shares are converted into the fund currency and then used to buy stock. This ensures that only one currency transaction is done. In your specific example the fund currency will be USD so your purchase of the shares (assuming there are no sellers and creation occurs) will be converted from GBP to USD and held in that currency in the fund. The fund then trades entirely in USD to avoid currency risk. When you want to sell your exposure (supposing redemption occurs) enough holdings required to redeem your money are sold to get cash in USD and then converted to GBP before paying you. This means that trading activity where there is no need to convert to GBP (or any other currency) does not incur currency conversion costs. In practice funds will always have some cash (or cash equivalents) on hand to pay out redemptions and will have an idea of the number and size of redemptions each calendar period so will use futures and swaps to mitigate FX risk. Where the same firm has two funds traded in different currencies with the same objectives it is likely that one is a wrapper for the other such that one simply converts the currency and buys the other currency denominated ETF. As these are exchange traded funds with a price in GBP the amount you pay for the ETF or gain on selling it is the price given and you will not have to consider currency exchange as that should be done internally as explained above. However, there can be a (temporary) arbitrage opportunity if the price in GBP does not reflect the price in USD and the exchange rate put together.","title":""},{"docid":"311192","text":"\"Bit hesitant to put this in an answer as I don't know if specific investment advice is appropriate, but this has grown way too long for a comment. The typical answer given for people who don't have the time, experience, knowledge or inclination to pick specific stocks to hold should instead invest in ETFs (exchange-traded index funds.) What these basically do is attempt to simulate a particular market or stock exchange. An S&P 500 index fund will (generally) attempt to hold shares in the stocks that make up that index. They only have to follow an index, not try to beat it so are called \"\"passively\"\" managed. They have very low expense ratios (far below 1%) and are considered a good choice for investors who want to hold stock without significant effort or expense and who's main goal is time in the market. It's a contentious topic but on average an index (and therefore an index fund) will go even with or outperform most actively managed funds. With a sufficiently long investment horizon, which you have, these may be ideal for you. Trading in ETFs is also typically cheap because they are traded like stock. There are plenty of low-fee online brokers and virtually all will allow trading in ETFs. My broker even has a list of several hundred popular ETFs that can be traded for free. The golden rule in investing is that you should never buy into something you don't understand. Don't buy individual stock with little information: it's often little more than gambling. The same goes for trading platforms like Loyal3. Don't use them unless you know their business model and what they stand to gain from your custom. As mentioned I can trade certain funds for free with my broker, but I know why they can offer that and how they're still making money.\"","title":""},{"docid":"29184","text":"\"Does the bolded sentence apply for ETFs and ETF companies? No, the value of an ETF is determined by an exchange and thus the value of the share is whatever the trading price is. Thus, the price of an ETF may go up or down just like other securities. Money market funds can be a bit different as the mutual fund company will typically step in to avoid \"\"Breaking the Buck\"\" that could happen as a failure for that kind of fund. To wit, must ETF companies invest a dollar in the ETF for every dollar that an investor deposited in this aforesaid ETF? No, because an ETF is traded as shares on the market, unless you are using the creation/redemption mechanism for the ETF, you are buying and selling shares like most retail investors I'd suspect. If you are using the creation/redemption system then there are baskets of other securities that are being swapped either for shares in the ETF or from shares in the ETF.\"","title":""},{"docid":"9672","text":"\"You're talking about money in a savings account, and avoiding the risks posed by an ongoing crisis, and avoiding risk. If you are risk-averse, and likely to need your money in the short term, you should not put your money in the stock market, even in \"\"safe\"\" stocks like P&G/Coca-Cola/etc. Even these safe stocks are at risk of wild price swings in the short- to intermediate-term, especially in the event of international crises such as major European debt defaults and the like. These stocks are suitable for long-term growth objectives, but they are not as a replacement for a savings account. Coca-Cola lost a third of its value between 2007 and 2009. (It's recovered, and is currently doing better than ever.) P&G went from $74/share to $46/share. (It's partially recovered and back at $63). On the other hand, these stocks may indeed be suitable as long-term investments to protect you against local currency inflation. And yes, they even pay dividends. If you're after this investment, a good option is probably a sector-specific exchange-traded fund, such as a consumer-staples ETF. It will likely be more diversified and safer than anything you could come up with using a list of individual stocks. You can also investigate recommendations that show up when you search for a \"\"defensive ETF\"\". If you do not wish to buy the ETF directly, you can also look at listings of the ETF's holdings. Read the prospectus for an idea of the risks associated with these funds. You can buy these funds with any brokerage that gives you access to US stock exchanges.\"","title":""},{"docid":"119819","text":"\"You seem to be assuming that ETFs must all work like the more traditional closed-end funds, where the market price per share tends—based on supply and demand—to significantly deviate from the underlying net asset value per share. The assumption is simplistic. What are traditionally referred to as closed-end funds (CEFs), where unit creation and redemption are very tightly controlled, have been around for a long time, and yes, they do often trade at a premium or discount to NAV because the quantity is inflexible. Yet, what is generally meant when the label \"\"ETF\"\" is used (despite CEFs also being both \"\"exchange-traded\"\" and \"\"funds\"\") are those securities which are not just exchange-traded, and funds, but also typically have two specific characteristics: (a) that they are based on some published index, and (b) that a mechanism exists for shares to be created or redeemed by large market participants. These characteristics facilitate efficient pricing through arbitrage. Essentially, when large market participants notice the price of an ETF diverging from the value of the shares held by the fund, new units of the ETF can get created or redeemed in bulk. The divergence quickly narrows as these participants buy or sell ETF units to capture the difference. So, the persistent premium (sometimes dear) or discount (sometimes deep) one can easily witness in the CEF universe tend not to occur with the typical ETF. Much of the time, prices for ETFs will tend to be very close to their net asset value. However, it isn't always the case, so proceed with some caution anyway. Both CEF and ETF providers generally publish information about their funds online. You will want to find out what is the underlying Net Asset Value (NAV) per share, and then you can determine if the market price trades at a premium or a discount to NAV. Assuming little difference in an ETF's price vs. its NAV, the more interesting question to ask about an ETF then becomes whether the NAV itself is a bargain, or not. That means you'll need to be more concerned with what stocks are in the index the fund tracks, and whether those stocks are a bargain, or not, at their current prices. i.e. The ETF is a basket, so look at each thing in the basket. Of course, most people buy ETFs because they don't want to do this kind of analysis and are happy with market average returns. Even so, sector-based ETFs are often used by traders to buy (or sell) entire sectors that may be undervalued (or overvalued).\"","title":""},{"docid":"130188","text":"ETFs trade on specific exchanges. If your broker deals with those exchanges, you should have access to the ETF. If your broker does not deal with that exchange, then you will not have access through that broker. This is different than, say, mutual funds, which don't trade on the exchanges are proprietary to certain brokerages or financial institutions.","title":""},{"docid":"489103","text":"\"Ask your trading site for their definition of \"\"ETF\"\". The term itself is overloaded/ambiguous. Consider: If \"\"ETF\"\" is interpreted liberally, then any fund that trades on a [stock] exchange is an exchange-traded fund. i.e. the most literal meaning implied by the acronym itself. Whereas, if \"\"ETF\"\" is interpreted more narrowly and in the sense that most market participants might use it, then \"\"ETF\"\" refers to those exchange-traded funds that specifically have a mechanism in place to ensure the fund's current price remains close to its net asset value. This is not the case with closed-end funds (CEFs), which often trade at either a premium or a discount to their underlying net asset value.\"","title":""},{"docid":"304023","text":"\"ETF Creation and Redemption Process notes the process: While ETF trading occurs on an exchange like stocks, the process by which their shares are created is significantly different. Unless a company decides to issue more shares, the supply of shares of an individual stock trading in the marketplace is finite. When demand increases for shares of an ETF, however, Authorized Participants (APs) have the ability to create additional shares on demand. Through an \"\"in kind\"\" transfer mechanism, APs create ETF units in the primary market by delivering a basket of securities to the fund equal to the current holdings of the ETF. In return, they receive a large block of ETF shares (typically 50,000), which are then available for trading in the secondary market. This ETF creation and redemption process helps keep ETF supply and demand in continual balance and provides a \"\"hidden\"\" layer of liquidity not evident by looking at trading volumes alone. This process also works in reverse. If an investor wants to sell a large block of shares of an ETF, even if there seems to be limited liquidity in the secondary market, APs can readily redeem a block of ETF shares by gathering enough shares of the ETF to form a creation unit and then exchanging the creation unit for the underlying securities. Thus, the in-kind swap to the underlying securities is only done by APs so the outflow would be these individuals taking a large block of the ETF and swapping it for the underlying securities. The APs would be taking advantage of the difference between what the ETF's trading value and the value of the underlying securities.\"","title":""},{"docid":"129070","text":"You could use a stock-only ISA and invest in Exchange Traded Funds (ETFs). ETFs are managed mutual funds that trade on open exchanges in the same manner as stocks. This changes the specific fund options you have open to you, but there are so many ETFs at this point that any sector you want to invest in is almost certainly represented.","title":""},{"docid":"402046","text":"Ending up with nothing is an unlikely situation unless you invest 100% in a company stock and the company goes under. In order to give you a good answer we need to see what options your employer gives for 401k investments. The best advice would be to take a list of all options that your employer allows and talk with a financial advisor. Here are a few options that you may or may not have as an option from an employer: Definitions from wikipedia: A target-date fund – also known as a lifecycle, dynamic-risk or age-based fund – is a collective investment scheme, usually a mutual fund, designed to provide a simple investment solution through a portfolio whose asset allocation mix becomes more conservative as the target date (usually retirement) approaches. An index fund or index tracker is a collective investment scheme (usually a mutual fund or exchange-traded fund) that aims to replicate the movements of an index of a specific financial market... An exchange-traded fund (ETF) is an investment fund traded on stock exchanges, much like stocks.[1] An ETF holds assets such as stocks, commodities, or bonds, and trades close to its net asset value over the course of the trading day. Most ETFs track an index, such as a stock index or bond index. ETFs may be attractive as investments because of their low costs, tax efficiency, and stock-like features. The capital stock (or stock) of an incorporated business constitutes the equity stake of its owners. Which one can you lose everything in? You can lose everything in stocks by the company going under. In Index funds the entire market that it follows would have to collapse. The chances are slim here since the index made up of several companies. The S&P 500 is made up of 500 leading companies publicly traded in the U.S. A Pacific-Europe index such as MSCI EAFE Index is made up of 907 companies. The chances of losing everything in an ETF are also slim. The ETF that follows the S&P 500 is made up of 500 companies. An Pacific-Europe ETF such as MSCI EAFE ETF is made up of 871 companies. Target date funds are also slim to lose everything. Target date funds are made up of several companies like indexes and etfs and also mix in bonds and other investments depending on your age. What would I recommend? I would recommend the Index funds and/or ETFs that have the lowest fee that make up the following strategy for your age: Why Not Target Date Funds or Stocks? Target date funds have high fees. Later in life when you are closer to retirement you may want to add bonds to your portfolio. At that time if this is the only option to add bonds then you can change your elections. Stocks are too risky for you with your current knowledge. If your company matches by buying their stock you may want to consider reallocating that stock at certain points to your Index funds or ETFs.","title":""},{"docid":"120059","text":"\"Generally, ETFs work on the basis that there exists a pair of values that can be taken at any moment in time: A Net Asset Value of each share in the fund and a trading market price of each share in the fund. It may help to picture these in baskets of about 50,000 shares for the creation/redemption process. If the NAV is greater than the market price, then arbitrageurs will buy up shares at the market price and do an \"\"in-kind\"\" transaction that will be worth the NAV value that the arbitrageurs could turn around and sell for an immediate profit. If the market price is greater than the NAV, then the arbitrageurs will buy up the underlying securities that can be exchanged \"\"in-kind\"\" for shares in the fund that can then be sold on the market for an immediate profit. What is the ETF Creation/Redemption Mechanism? would be a source on this though I imagine there are others. Now, in the case of VXX, there is something to be said for how much trading is being done and what impact this can have. From a July 8, 2013 Yahoo Finance article: At big option trade in the iPath S&P 500 VIX Short-Term Futures Note is looking for another jump in volatility. More than 250,000 VXX options have already traded, twice its daily average over the last month. optionMONSTER systems show that a trader bought 13,298 August 26 calls for the ask price of $0.24 in volume that was 6 times the strike's previous open interest, clearly indicating new activity. Now the total returns of the ETF are a combination of changes in share price plus what happens with the distributions which could be held as cash or reinvested to purchase more shares.\"","title":""},{"docid":"349668","text":"This is more than likely a thing about your financial institution and the exchanges where they trade shares. Some exchanges cannot/will not handle odd lot transactions. Most established brokerages have software and accounting systems that will deal in round lots with the exchanges, but can track your shares individually. Sometimes specific stocks cannot be purchased in odd lots due to circumstances specific to that stock (trading only on a specific exchange, for example). Most brokerages offer dollar-cost averaging programs, but may limit which stocks are eligible, due to odd lot and partial share purchases. Check with your brokerage to see if they can support odd lot and/or DCA purchases. You may find another similar ETF with similar holdings that has better trading conditions, or might consider an open-end mutual fund with similar objectives. Mutual funds allow partial share purchases (you have $100 to invest today, and they issue you 35.2 shares, for example).","title":""},{"docid":"472663","text":"\"An Exchange-Traded Fund (ETF) is a special type of mutual fund that is traded on the stock exchange like a stock. To invest, you buy it through a stock broker, just as you would if you were buying an individual stock. When looking at a mutual fund based in the U.S., the easiest way to tell whether or not it is an ETF is by looking at the ticker symbol. Traditional mutual funds have ticker symbols that end in \"\"X\"\", and ETFs have ticker symbols that do not end in \"\"X\"\". The JPMorgan Emerging Markets Equity Fund, with ticker symbol JFAMX, is a traditional mutual fund, not an ETF. JPMorgan does have ETFs; the JPMorgan Diversified Return Emerging Markets Equity ETF, with ticker symbol JPEM, is an example. This ETF invests in similar stocks as JFAMX; however, because it is an index-based fund instead of an actively managed fund, it has lower fees. If you aren't sure about the ticker symbol, the advertising/prospectus of any ETF should clearly state that it is an ETF. (In the example of JPEM above, they put \"\"ETF\"\" right in the fund name.) If you don't see ETF mentioned, it is most likely a traditional mutual fund. Another way to tell is by looking at the \"\"investment minimums\"\" of the fund. JFAMX has a minimum initial investment of $1000. ETFs, however, do not have an investment minimum listed; because it is traded like a stock, you simply buy whole shares at whatever the current share price is. So if you look at the \"\"Fees and Investment Minimums\"\" section of the JPEM page, you'll see the fees listed, but not any investment minimums.\"","title":""},{"docid":"367960","text":"\"I think you are asking about actively managed funds vs. indexes and possibly also vs. diversified funds like target date funds. This is also related to the question of mutual fund vs. ETF. First, a fund can be either actively managed or it can attempt to track an index. An actively managed fund has a fund manager who tries to find the best stocks to invest in within some constraints, like \"\"this fund invests in large cap US companies\"\". An index fund tries to match as closely as possible the performance of an index like the S&P 500. A fund may also try to offer a portfolio that is suitable for someone to put their entire account into. For example, a target date fund is a fund that may invest in a mix of stocks, bonds and foreign stock in a proportion that would be appropriate to someone expecting to retire in a certain year. These are not what people tend to think of as the canonical examples of mutual funds, even though they share the same legal structure and investment mechanisms. Secondly, a fund can either be a traditional mutual fund or it can be an exchange traded fund (ETF). To invest in a traditional mutual fund, you send money to the fund, and they give you a number of shares equal to what that money would have bought of the net asset value (NAV) of the fund at the end of trading on the day they receive your deposit, possibly minus a sales charge. To invest in an ETF, you buy shares of the ETF on the stock market like any other stock. Under the covers, an ETF does have something similar to the mechanism of depositing money to get shares, but only big traders can use that, and it's not used for investing, but only for people who are making a market in the stock (if lots of people are buying VTI, Big Dealer Co will get 100,000 shares from Vanguard so that they can sell them on the market the next day). Historically and traditionally, ETFs are associated with an indexing strategy, while if not specifically mentioned, people assume that traditional mutual funds are actively managed. Many ETFs, notably all the Vanguard ETFs, are actually just a different way to hold the same underlying fund. The best way to understand this is to read the prospectus for a mutual fund and an ETF. It's all there in reasonably plain English.\"","title":""},{"docid":"531180","text":"You can look into specific market targeted mutual funds or ETF's. For Norway, for example, look at NORW. If you want to purchase specific stocks, then you'd better be ready to trade on local stock exchanges in local currency. ETrade allows trading on some of the international stock exchanges (in Asia they have Hong Kong and Japan, in Europe they have the UK, Germany and France, and in the Americas they have the US and Canada). Some of the companies you're interested in might be trading there.","title":""},{"docid":"39265","text":"In addition to the higher risk as pointed out by @JamesRoth, you also need to consider that there are regulations against 'naked shorting' so you generally need to either own the security, or have someone that is willing to 'loan' the security to you in order to sell short. If you own a stock you are shorting, the IRS could view the transaction as a Sell followed by a buy taking place in a less than 30 day period and you could be subject to wash-sale rules. This added complexity (most often the finding of someone to loan you the security you are shorting) is another reason such trades are considered more advanced. You should also be aware that there are currently a number of proposals to re-instate the 'uptick rule' or some circuit-breaker variant. Designed to prevent short-sellers from driving down the price of a stock (and conducting 'bear raids etc) the first requires that a stock trade at the same or higher price as prior trades before you can submit a short. In the latter shorting would be prohibited after a stock price had fallen a given percentage in a given amount of time. In either case, should such a rule be (re)established then you could face limitations attempting to execute a short which you would not need to worry about doing simple buys or sells. As to vehicles that would do this kind of thing (if you are convinced we are in a bear market and willing to take the risk) there are a number of ETF's classified as 'Inverse Exchange Traded Funds (ETF's) for a variety of markets that via various means seek to deliver a return similar to that of 'shorting the market' in question. One such example for a common broad market is ticker SH the ProShares Short S&P500 ETF, which seeks to deliver a return that is the inverse of the S&P500 (and as would be predicted based on the roughly +15% performance of the S&P500 over the last 12 months, SH is down roughly -15% over the same period). The Wikipedia article on inverse ETF's lists a number of other such funds covering various markets. I think it should be noted that using such a vehicle is a pretty 'aggressive bet' to take in reaction to the belief that a bear market is imminent. A more conservative approach would be to simply take money out of the market and place it in something like CD's or Treasury instruments. In that case, you preserve your capital, regardless of what happens in the market. Using an inverse ETF OTOH means that if the market went bull instead of bear, you would lose money instead of merely holding your position.","title":""},{"docid":"369266","text":"A stock, bond or ETF is basically a commodity. Where you bought it does not really matter, and it has a value in USD only inasmuch as there is a current market price quoted at an American exchange. But nothing prevents you from turning around and selling it on a European exchange where it is also listed for an equivalent amount of EUR (arbitrage activities of investment banks ensure that the price will be equivalent in regard to the current exchange rate). In fact, this can be used as a cheap form of currency conversion. For blue chips at least this is trivial; exotic securities might not be listed in Europe. All you need is a broker who allows you to trade on European exchanges and hold an account denominated in EUR. If necessary, transfer your securities to a broker who does, which should not cost more than a nominal fee. Mutual funds are a different beast though; it might be possible to sell shares on an exchange anyway, or sell them back to the issuer for EUR. It depends. In any case, however, transferring 7 figure sums internationally can trigger all kinds of tax events and money laundering investigations. You really need to hire a financial advisor who has international investment experience for this kind of thing, not ask a web forum!","title":""},{"docid":"65663","text":"\"@sdg's answer is spot-on with the advice to avoid repeated conversions, but I'd like to provide some specifics on the fees involved: Each time you round-trip Canadian dollars (CAD) through a U.S.-dollar (USD) priced security at TD Waterhouse and leave your proceeds in CAD, you're paying a total foreign exchange fee – implied in their rate spread – of about 3%, give or take. That's ~3% per buy & sell combination, or ~1.5% on each end. You can imagine if you trade back & forth frequently, you can quickly lose a lot of money. Do it back and forth ten times in a year and you're out ~30% on the fees alone! The TD U.S. Money Market Fund (TDB166) that TD Waterhouse is referring to has no direct commission to buy or sell, but it does have a Management Expense Ratio (MER) of 0.20% per year – basically a fee which is deducted from the fund's returns (which, today, are also close to zero.) Practically speaking, that's a very slim fee to hold some USD in your Canadian dollar TFSA. While 0.20% is cheap, a point to keep in mind is if you maintain a significant USD balance, you are maintaining currency risk: You can lose money in CAD terms if the CAD appreciates vs. USD. Additional references: Canadian Capitalist describes TD Waterhouse and the use of TDB166 and \"\"wash trades\"\" at How to \"\"Wash\"\" Your Trade? He's referring to RRSPs, but the same applies to TFSAs, which came out after the post was written. Canadian Couch Potato has two relevant articles: Are US-listed ETFs Really Cheaper? and Lowering Your Currency Exchange Fees.\"","title":""},{"docid":"84800","text":"\"Your broker, Ameritrade, offers a variety of Exchange Traded Funds (ETFs) that you can buy and sell with zero commission. An ETF is like a mutual fund, but you buy and sell shares the same way you buy and sell shares of stocks. From your point of view, the relevance of this is that you can buy and sell as many or as few shares as you like, even down to a single share. Note that to get the commission-free trades on the available ETFs you have to sign up for it in your account profile. Be sure to do that before you enter any buy orders. You'll want to start by looking at the Ameritrade's list of commission-free ETFs. Notice that they are divided into different categories: stocks, bonds, international, and commodities. Which categories you pick from will depend on your personal investing goals, time horizon, risk tolerance, and so on. There are lots of questions and answers on this site that talk about asset allocation. You should read them, as it is the most important decision you will make with your portfolio. The other thing you want to be aware of is the expense ratio for each fund. These expenses reduce the fund's return (they are included in the calculation of the net asset value of the shares), so lower is definitely better. Personally, I wouldn't even consider paying more than about 0.10% (commonly read \"\"10 basis points\"\" or \"\"10 bp\"\") for a broad-based domestic stock fund. For a sectoral fund you might put up with as much as 20 bp in expenses. Bond funds tend to be a little more expensive, so maybe allow as much as 25 bp, and likewise for international funds. I've never invested in commodity funds, so I'll let someone else opine on appropriate expense ratios for those. Once you've decided what funds you want (and have signed up for commission-free trades), all you have to do is enter the trade orders. The website where you manage your account has tutorials on how to do that. After that you should be all set. Good luck with your investing!\"","title":""},{"docid":"224765","text":"\"An ETF does not track any one individual stock. It \"\"is a marketable security that tracks an index, a commodity, bonds, or a basket of assets like an index fund.\"\" Check out this link to learn more about ETFs. The easiest way see what ETF tracks a stock is to determine what sector and industry that company is in and find some ETF that trade it. The ETF will likely trade that stock, assuming that its market cap and exchange it trades on fits within the parameters of the ETF.\"","title":""},{"docid":"151203","text":"A derivative in finance is simply any asset whose value is based on the value of another asset or based on the value of a group of assets. A derivative contract is a type of contract (usually a 'standardized contract') with specific payout instruction based on the price changes of a different asset. The basic idea is that it becomes easier to make a claim to an asset or property (and profit from this claim), without needing to physically transfer it (or even the title to said asset), and use much less capital to do so (reduce risk). They become problematic when multiple people may have claims to the real asset, or when the value of the derivatives changes very quickly or are hard to calculate. There are also liquidity problems the further you get from the real asset. This is not a problem for all kinds of derivatives contracts. And you must recognize that derivatives are used colloquially in a way that has nothing to do with reality to cause fear in people/investors that are not financially savvy. Many derivatives also have dubious or no economic purposes such that regulators don't allow them to be traded since they can't see how it is different from gambling. This is seen in financial markets that are less liberalized or cultures with puritanical backgrounds. Typically the trick is to convince regulators that the derivative or financial product helps with reducing risk and hedging and it will get approved. I've mentioned some terminology, but this depends specifically on what kind of derivatives contract you become interested in. Swaps, Credit Default Swaps, Futures, Options, Options on Futures, Leveraged Exchange Traded Funds, Inverse Leveraged Exchange Traded Funds, warrants, and more all have their own terminology. How to trade them in a simulation? It all depends on which financial product you really become interested in.","title":""},{"docid":"276983","text":"You haven't looked very far if you didn't find index tracking exchange-traded funds (ETFs) on the Toronto Stock Exchange. There are at least a half dozen major exchange-traded fund families that I'm aware of, including Canadian-listed offerings from some of the larger ETF providers from the U.S. The Toronto Stock Exchange (TSX) maintains a list of ETF providers that have products listed on the TSX.","title":""},{"docid":"515643","text":"So, couple of things. Firstly, every international ETF includes risk disclosure language in the prospectus covering both market disruption events as well as geopolitical risk, so the sponsor would be pretty well insulated from direct liability for anything. If the Russian market were truly shut down there are true-up mechanisms in place but in the scenario you're describing the market is still open, it's just only a few participants can trade in it. First thing to do is shut down creates- that is, allow no new money to come into the fund. This at least prevents your problem from getting bigger. Second you're going to switch all redemptions to in kind only. MV itself can't trade in the underlying so they're kind of jammed here. An ETF sponsor can't really refuse your redemption request (can delay, but only for a short time), but they can control the form in which they respond to it. What theoretically should happen here is an AP not subject to sanctions will step in and handle redemptions. Issue is, they'll probably charge for this so you should expect the fund to start trading at a discount to NAV (you, as an investor, sell to them cheaply, they submit a redemption request, then sell the stocks locally). Someone else has pointed that market makers will start stat arbing the fund using correlated/substitute instruments, which totally will help keep things in line, but my guess is that you'd still see the name trading away from NAV regardless. Driver of this will be the amount of money desperate to get out - if investors are content to wait the sanctions out who knows.","title":""},{"docid":"205280","text":"\"According to what little information is available currently, this fund is most akin to an actively managed exchange traded fund rather than an investment trust. An investment trust is an actively managed, closed-end fund that is tradeable on the stock market. \"\"Closed-end\"\" means that there are a fixed number of shares available for trading, so if you wish to buy or sell shares in a closed-end fund you need to find someone willing to sell or buy shares. \"\"Actively managed\"\" means that the assets are selected by the fund managers in the belief that they will perform well. This is in contrast to a \"\"passively managed\"\" fund which simply tracks an underlying index. The closed-end nature of investment trusts means that the share price is not well correlated to the value of the underlying assets. Indeed, almost all UK investment trusts trade at a significant discount to their net asset value. This reflects their historic poor performance and relatively weak liquidity. Of course there are some exceptions to this. Examples of open-end funds are unit trust (US = mutual funds) and ETFs (exchange traded funds). They are \"\"open-end\"\" funds in the sense that the number of shares/units available will change according to demand. Most importantly, the price of a share/unit will be strongly correlated to the net asset value of the underlying portfolio. In general, for an open-end fund, if the net asset value of the fund is X and there are Y shares/units outstanding, then the price of a share/unit will be X/Y. Historic data shows that passively managed funds (index trackers) \"\"always\"\" outperform actively managed funds in the long term. One of the big issues with actively managed funds is they have relatively high management fees. The Peoples Trust will be charging about 1% with a promise that this should come down over time. Compare this to a fee of 0.05% on a large, major market index tracking ETF. Further, the 1% headline fee being touted by Peoples Trust is a somewhat misleading, since they are paying their employees bonuses with shares in the fund. This will cause dilution of the net asset value per share and can be read as addition management fees by proxy. Since competent fund managers will demand high incomes, bonus shares could easily double the management fees, depending on the size of the fund. In summary, history has shown that the promises of active fund managers rarely (if ever) come to fruition. Personally, I would not consider this to be an attractive investment and would look more towards a passively managed major market index ETF with low management fees.\"","title":""},{"docid":"479420","text":"Mutual funds buy (and sell) shares in companies in accordance with the policies set forth in their prospectus, not according to the individual needs of an investor, that is, when you invest money in (or withdraw money from) a mutual fund, the manager buys or sells whatever shares that, in the manager's judgement, will be the most appropriate ones (consistent with the investment policies). Thus, a large-cap mutual fund manager will not buy the latest hot small-cap stock that will likely be hugely profitable; he/she must choose only between various large capitalization companies. Some exchange-traded funds are fixed baskets of stocks. Suppose you will not invest in a company X as a matter of principle. Unless a mutual fund prospectus says that it will not invest in X, you may well end up having an investment in X at some time because the fund manager bought shares in X. With such an ETF, you know what is in the basket, and if the basket does not include stock in X now, it will not own stock in X at a later date. Some exchange-traded funds are constructed based on some index and track the index as a matter of policy. Thus, you will not be investing in X unless X becomes part of the index because Standard or Poor or Russell or somebody changed their minds, and the ETF buys X in order to track the index. Finally, some ETFs are exactly like general mutual funds except that you can buy or sell ETF shares at any time at the price at the instant that your order is executed whereas with mutual funds, the price of the mutual fund shares that you have bought or sold is the NAV of the mutual fund shares for that day, which is established based on the closing prices at the end of the trading day of the stocks, bonds etc that the fund owns. So, you might end up owning stock in X at any time based on what the fund manager thinks about X.","title":""},{"docid":"322725","text":"In the past 10 years there have been mutual funds that would act as a single bucket of stocks and bonds. A good example is Fidelity's Four In One. The trade off was a management fee for the fund in exchange for having to manage the portfolio itself and pay separate commissions and fees. These days though it is very simple and pretty cheap to put together a basket of 5-6 ETFs that would represent a balanced portfolio. Whats even more interesting is that large online brokerage houses are starting to offer commission free trading of a number of ETFs, as long as they are not day traded and are held for a period similar to NTF mutual funds. I think you could easily put together a basket of 5-6 ETFs to trade on Fidelity or TD Ameritrade commission free, and one that would represent a nice diversified portfolio. The main advantage is that you are not giving money to the fund manager but rather paying the minimal cost of investing in an index ETF. Overall this can save you an extra .5-1% annually on your portfolio, just in fees. Here are links to commission free ETF trading on Fidelity and TD Ameritrade.","title":""},{"docid":"328699","text":"\"The London Stock Exchange offers a wealth of exchange traded products whose variety matches those offered in the US. Here is a link to a list of exchange traded products listed on the LSE. The link will take you to the list of Vanguard offerings. To view those offered by other managers, click on the letter choices at the top of the page. For example, to view the iShares offerings, click on \"\"I\"\". In the case of Vanguard, the LSE listed S&P500 ETF is traded under the code VUSA. Similarly, the Vanguard All World ETF trades under the code VWRL. You will need to be patient viewing iShares offerings since there are over ten pages of them, and their description is given by the abbreviation \"\"ISH name\"\". Almost all of these funds are traded in GBP. Some offer both currency hedged and currency unhedged versions. Obviously, with the unhedged version you are taking on additional currency risk, so if you wish to avoid currency risk then choose a currency hedged version. Vanguard does not appear to offer currency hedged products in London while iShares does. Here is a list of iShares currency hedged products. As you can see, the S&P500 currency hedged trades under the code IGUS while the unhedged version trades under the code IUSA. The effects of BREXIT on UK markets and currency are a matter of opinion and difficult to quantify currently. The doom and gloom warnings of some do not appear to have materialised, however the potential for near-term volatility remains so longs as the exit agreement is not formalised. In the long-term, I personally believe that BREXIT will, on balance, be a positive for the UK, but that is just my opinion.\"","title":""},{"docid":"454224","text":"A mutual fund has several classes of shares that are charged different fees. Some shares are sold through brokers and carry a sales charge (called load) that compensates the broker in lieu of a fee that the broker would charge the client for the service. Vanguard does not have sales charge on its funds and you don't need to go through a broker to buy its shares; you can buy directly from them. Admiral shares of Vanguard funds are charged lower annual expenses than regular shares (yes, all mutual funds charge expenses for fund adninistration that reduce the return that you get, and Vanguard has some of the lowest expense ratios) but Admiral shares are available only for large investments, typically $50K or so. If you have invested in a Vanguard mutual fund, your shares can be set to automatically convert to Admiral shares when the investment reaches the right level. A mutual fund manager can buy and sell stocks to achieve the objectives of the fund, so what stockes you are invested in as a share holder in a mutual fund will typically be unknown to you on a day-to-day basis. On the other hand, Exchange-traded funds (ETFs) are fixed baskets of stocks, and you can buy shares in the ETF. These shares are bought and sold through a broker (so you pay a transaction fee each time) but expenses are lower since there is no manager to buy and sell stocks: the basket is fixed. Many ETFs follow specific market indexes (e.g. S&P 500). Another difference between ETFs and mutual funds is that you can buy and sell ETFs at any time of the day just as if you could if you held stocks. With mutual funds, any buy and sell requests made during the day are processed at the end of the day and the value of the shares that you buy or sell is determined by the closing price of the stocks held by the mutual fund. With ETFs, you are getting the intra-day price at the time the buy or sell order is executed by your broker.","title":""},{"docid":"183898","text":"It is true that this is possible, however, it's very remote in the case of the large and reputable fund companies such as Vanguard. FDIC insurance protects against precisely this for bank accounts, but mutual funds and ETFs do not have an equivalent to FDIC insurance. One thing that does help you in the case of a mutual fund or ETF is that you indirectly (through the fund) own actual assets. In a cash account at a bank, you have a promise from the bank to pay, and then the bank can go off and use your money to make loans. You don't in any sense own the bank's loans. With a fund, the fund company cannot (legally) take your money out of the fund, except to pay the expense ratio. They have to use your money to buy stocks, bonds, or whatever the fund invests in. Those assets are then owned by the fund. Legally, a mutual fund is a special kind of company defined in the Investment Company Act of 1940, and is a separate company from the investment advisor (such as Vanguard): http://www.sec.gov/answers/mfinvco.htm Funds have their own boards, and in principle a fund board can even fire the company advising the fund, though this is not likely since boards aren't usually independent. (a quick google found this article for more, maybe someone can find a better one: http://www.marketwatch.com/story/mutual-fund-independent-board-rule-all-but-dead) If Vanguard goes under, the funds could continue to exist and get a new adviser, or could be liquidated with investors receiving whatever the assets are worth. Of course, all this legal stuff doesn't help you with outright fraud. If a fund's adviser says it bought the S&P 500, but really some guy bought himself a yacht, Madoff-style, then you have a problem. But a huge well-known ETF has auditors, tons of different employees, lots of brokerage and exchange traffic, etc. so to me at least it's tough to imagine a risk here. With a small fund company with just a few people - and there are lots of these! - then there's more risk, and you'd want to carefully look at what independent agent holds their assets, who their auditors are, and so forth. With regular mutual funds (not ETFs) there are more issues with diversifying across fund companies: With ETFs, there probably isn't much downside to diversifying since you could buy them all from one brokerage account. Maybe it even happens naturally if you pick the best ETFs you can find. Personally, I would just pick the best ETFs and not worry about advisor diversity. Update: maybe also deserving a mention are exchange-traded notes (ETNs). An ETN's legal structure is more like the bank account, minus the FDIC insurance of course. It's an IOU from the company that runs the ETN, where they promise to pay back the value of some index. There's no investment company as with a fund, and therefore you don't own a share of any actual assets. If the ETN's sponsor went bankrupt, you would indeed have a problem, much more so than if an ETF's sponsor went bankrupt.","title":""}],"string":"[\n {\n \"docid\": \"332924\",\n \"text\": \"\\\"I recommend avoiding trading directly in commodities futures and options. If you're not prepared to learn a lot about how futures markets and trading works, it will be an experience fraught with pitfalls and lost money – and I am speaking from experience. Looking at stock-exchange listed products is a reasonable approach for an individual investor desiring added diversification for their portfolio. Still, exercise caution and know what you're buying. It's easy to access many commodity-based exchange-traded funds (ETFs) on North American stock exchanges. If you already have low-cost access to U.S. markets, consider this option – but be mindful of currency conversion costs, etc. Yet, there is also a European-based company, ETF Securities, headquartered in Jersey, Channel Islands, which offers many exchange-traded funds on European exchanges such as London and Frankfurt. ETF Securities started in 2003 by first offering a gold commodity exchange-traded fund. I also found the following: London Stock Exchange: Frequently Asked Questions about ETCs. The LSE ETC FAQ specifically mentions \\\"\\\"ETF Securities\\\"\\\" by name, and addresses questions such as how/where they are regulated, what happens to investments if \\\"\\\"ETF Securities\\\"\\\" were to go bankrupt, etc. I hope this helps, but please, do your own due diligence.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"161201\",\n \"text\": \"Your assumption that funds sold in GBP trade in GBP is incorrect. In general funds purchase their constituent stocks in the fund currency which may be different to the subscription currency. Where the subscription currency is different from the fund currency subscriptions are converted into the fund currency before the extra money is used to increase holdings. An ETF, on the other hand, does not take subscriptions directly but by creation (and redemption) of shares. The principle is the same however; monies received from creation of ETF shares are converted into the fund currency and then used to buy stock. This ensures that only one currency transaction is done. In your specific example the fund currency will be USD so your purchase of the shares (assuming there are no sellers and creation occurs) will be converted from GBP to USD and held in that currency in the fund. The fund then trades entirely in USD to avoid currency risk. When you want to sell your exposure (supposing redemption occurs) enough holdings required to redeem your money are sold to get cash in USD and then converted to GBP before paying you. This means that trading activity where there is no need to convert to GBP (or any other currency) does not incur currency conversion costs. In practice funds will always have some cash (or cash equivalents) on hand to pay out redemptions and will have an idea of the number and size of redemptions each calendar period so will use futures and swaps to mitigate FX risk. Where the same firm has two funds traded in different currencies with the same objectives it is likely that one is a wrapper for the other such that one simply converts the currency and buys the other currency denominated ETF. As these are exchange traded funds with a price in GBP the amount you pay for the ETF or gain on selling it is the price given and you will not have to consider currency exchange as that should be done internally as explained above. However, there can be a (temporary) arbitrage opportunity if the price in GBP does not reflect the price in USD and the exchange rate put together.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"311192\",\n \"text\": \"\\\"Bit hesitant to put this in an answer as I don't know if specific investment advice is appropriate, but this has grown way too long for a comment. The typical answer given for people who don't have the time, experience, knowledge or inclination to pick specific stocks to hold should instead invest in ETFs (exchange-traded index funds.) What these basically do is attempt to simulate a particular market or stock exchange. An S&P 500 index fund will (generally) attempt to hold shares in the stocks that make up that index. They only have to follow an index, not try to beat it so are called \\\"\\\"passively\\\"\\\" managed. They have very low expense ratios (far below 1%) and are considered a good choice for investors who want to hold stock without significant effort or expense and who's main goal is time in the market. It's a contentious topic but on average an index (and therefore an index fund) will go even with or outperform most actively managed funds. With a sufficiently long investment horizon, which you have, these may be ideal for you. Trading in ETFs is also typically cheap because they are traded like stock. There are plenty of low-fee online brokers and virtually all will allow trading in ETFs. My broker even has a list of several hundred popular ETFs that can be traded for free. The golden rule in investing is that you should never buy into something you don't understand. Don't buy individual stock with little information: it's often little more than gambling. The same goes for trading platforms like Loyal3. Don't use them unless you know their business model and what they stand to gain from your custom. As mentioned I can trade certain funds for free with my broker, but I know why they can offer that and how they're still making money.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"29184\",\n \"text\": \"\\\"Does the bolded sentence apply for ETFs and ETF companies? No, the value of an ETF is determined by an exchange and thus the value of the share is whatever the trading price is. Thus, the price of an ETF may go up or down just like other securities. Money market funds can be a bit different as the mutual fund company will typically step in to avoid \\\"\\\"Breaking the Buck\\\"\\\" that could happen as a failure for that kind of fund. To wit, must ETF companies invest a dollar in the ETF for every dollar that an investor deposited in this aforesaid ETF? No, because an ETF is traded as shares on the market, unless you are using the creation/redemption mechanism for the ETF, you are buying and selling shares like most retail investors I'd suspect. If you are using the creation/redemption system then there are baskets of other securities that are being swapped either for shares in the ETF or from shares in the ETF.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"9672\",\n \"text\": \"\\\"You're talking about money in a savings account, and avoiding the risks posed by an ongoing crisis, and avoiding risk. If you are risk-averse, and likely to need your money in the short term, you should not put your money in the stock market, even in \\\"\\\"safe\\\"\\\" stocks like P&G/Coca-Cola/etc. Even these safe stocks are at risk of wild price swings in the short- to intermediate-term, especially in the event of international crises such as major European debt defaults and the like. These stocks are suitable for long-term growth objectives, but they are not as a replacement for a savings account. Coca-Cola lost a third of its value between 2007 and 2009. (It's recovered, and is currently doing better than ever.) P&G went from $74/share to $46/share. (It's partially recovered and back at $63). On the other hand, these stocks may indeed be suitable as long-term investments to protect you against local currency inflation. And yes, they even pay dividends. If you're after this investment, a good option is probably a sector-specific exchange-traded fund, such as a consumer-staples ETF. It will likely be more diversified and safer than anything you could come up with using a list of individual stocks. You can also investigate recommendations that show up when you search for a \\\"\\\"defensive ETF\\\"\\\". If you do not wish to buy the ETF directly, you can also look at listings of the ETF's holdings. Read the prospectus for an idea of the risks associated with these funds. You can buy these funds with any brokerage that gives you access to US stock exchanges.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"119819\",\n \"text\": \"\\\"You seem to be assuming that ETFs must all work like the more traditional closed-end funds, where the market price per share tends—based on supply and demand—to significantly deviate from the underlying net asset value per share. The assumption is simplistic. What are traditionally referred to as closed-end funds (CEFs), where unit creation and redemption are very tightly controlled, have been around for a long time, and yes, they do often trade at a premium or discount to NAV because the quantity is inflexible. Yet, what is generally meant when the label \\\"\\\"ETF\\\"\\\" is used (despite CEFs also being both \\\"\\\"exchange-traded\\\"\\\" and \\\"\\\"funds\\\"\\\") are those securities which are not just exchange-traded, and funds, but also typically have two specific characteristics: (a) that they are based on some published index, and (b) that a mechanism exists for shares to be created or redeemed by large market participants. These characteristics facilitate efficient pricing through arbitrage. Essentially, when large market participants notice the price of an ETF diverging from the value of the shares held by the fund, new units of the ETF can get created or redeemed in bulk. The divergence quickly narrows as these participants buy or sell ETF units to capture the difference. So, the persistent premium (sometimes dear) or discount (sometimes deep) one can easily witness in the CEF universe tend not to occur with the typical ETF. Much of the time, prices for ETFs will tend to be very close to their net asset value. However, it isn't always the case, so proceed with some caution anyway. Both CEF and ETF providers generally publish information about their funds online. You will want to find out what is the underlying Net Asset Value (NAV) per share, and then you can determine if the market price trades at a premium or a discount to NAV. Assuming little difference in an ETF's price vs. its NAV, the more interesting question to ask about an ETF then becomes whether the NAV itself is a bargain, or not. That means you'll need to be more concerned with what stocks are in the index the fund tracks, and whether those stocks are a bargain, or not, at their current prices. i.e. The ETF is a basket, so look at each thing in the basket. Of course, most people buy ETFs because they don't want to do this kind of analysis and are happy with market average returns. Even so, sector-based ETFs are often used by traders to buy (or sell) entire sectors that may be undervalued (or overvalued).\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"130188\",\n \"text\": \"ETFs trade on specific exchanges. If your broker deals with those exchanges, you should have access to the ETF. If your broker does not deal with that exchange, then you will not have access through that broker. This is different than, say, mutual funds, which don't trade on the exchanges are proprietary to certain brokerages or financial institutions.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"489103\",\n \"text\": \"\\\"Ask your trading site for their definition of \\\"\\\"ETF\\\"\\\". The term itself is overloaded/ambiguous. Consider: If \\\"\\\"ETF\\\"\\\" is interpreted liberally, then any fund that trades on a [stock] exchange is an exchange-traded fund. i.e. the most literal meaning implied by the acronym itself. Whereas, if \\\"\\\"ETF\\\"\\\" is interpreted more narrowly and in the sense that most market participants might use it, then \\\"\\\"ETF\\\"\\\" refers to those exchange-traded funds that specifically have a mechanism in place to ensure the fund's current price remains close to its net asset value. This is not the case with closed-end funds (CEFs), which often trade at either a premium or a discount to their underlying net asset value.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"304023\",\n \"text\": \"\\\"ETF Creation and Redemption Process notes the process: While ETF trading occurs on an exchange like stocks, the process by which their shares are created is significantly different. Unless a company decides to issue more shares, the supply of shares of an individual stock trading in the marketplace is finite. When demand increases for shares of an ETF, however, Authorized Participants (APs) have the ability to create additional shares on demand. Through an \\\"\\\"in kind\\\"\\\" transfer mechanism, APs create ETF units in the primary market by delivering a basket of securities to the fund equal to the current holdings of the ETF. In return, they receive a large block of ETF shares (typically 50,000), which are then available for trading in the secondary market. This ETF creation and redemption process helps keep ETF supply and demand in continual balance and provides a \\\"\\\"hidden\\\"\\\" layer of liquidity not evident by looking at trading volumes alone. This process also works in reverse. If an investor wants to sell a large block of shares of an ETF, even if there seems to be limited liquidity in the secondary market, APs can readily redeem a block of ETF shares by gathering enough shares of the ETF to form a creation unit and then exchanging the creation unit for the underlying securities. Thus, the in-kind swap to the underlying securities is only done by APs so the outflow would be these individuals taking a large block of the ETF and swapping it for the underlying securities. The APs would be taking advantage of the difference between what the ETF's trading value and the value of the underlying securities.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"129070\",\n \"text\": \"You could use a stock-only ISA and invest in Exchange Traded Funds (ETFs). ETFs are managed mutual funds that trade on open exchanges in the same manner as stocks. This changes the specific fund options you have open to you, but there are so many ETFs at this point that any sector you want to invest in is almost certainly represented.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"402046\",\n \"text\": \"Ending up with nothing is an unlikely situation unless you invest 100% in a company stock and the company goes under. In order to give you a good answer we need to see what options your employer gives for 401k investments. The best advice would be to take a list of all options that your employer allows and talk with a financial advisor. Here are a few options that you may or may not have as an option from an employer: Definitions from wikipedia: A target-date fund – also known as a lifecycle, dynamic-risk or age-based fund – is a collective investment scheme, usually a mutual fund, designed to provide a simple investment solution through a portfolio whose asset allocation mix becomes more conservative as the target date (usually retirement) approaches. An index fund or index tracker is a collective investment scheme (usually a mutual fund or exchange-traded fund) that aims to replicate the movements of an index of a specific financial market... An exchange-traded fund (ETF) is an investment fund traded on stock exchanges, much like stocks.[1] An ETF holds assets such as stocks, commodities, or bonds, and trades close to its net asset value over the course of the trading day. Most ETFs track an index, such as a stock index or bond index. ETFs may be attractive as investments because of their low costs, tax efficiency, and stock-like features. The capital stock (or stock) of an incorporated business constitutes the equity stake of its owners. Which one can you lose everything in? You can lose everything in stocks by the company going under. In Index funds the entire market that it follows would have to collapse. The chances are slim here since the index made up of several companies. The S&P 500 is made up of 500 leading companies publicly traded in the U.S. A Pacific-Europe index such as MSCI EAFE Index is made up of 907 companies. The chances of losing everything in an ETF are also slim. The ETF that follows the S&P 500 is made up of 500 companies. An Pacific-Europe ETF such as MSCI EAFE ETF is made up of 871 companies. Target date funds are also slim to lose everything. Target date funds are made up of several companies like indexes and etfs and also mix in bonds and other investments depending on your age. What would I recommend? I would recommend the Index funds and/or ETFs that have the lowest fee that make up the following strategy for your age: Why Not Target Date Funds or Stocks? Target date funds have high fees. Later in life when you are closer to retirement you may want to add bonds to your portfolio. At that time if this is the only option to add bonds then you can change your elections. Stocks are too risky for you with your current knowledge. If your company matches by buying their stock you may want to consider reallocating that stock at certain points to your Index funds or ETFs.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"120059\",\n \"text\": \"\\\"Generally, ETFs work on the basis that there exists a pair of values that can be taken at any moment in time: A Net Asset Value of each share in the fund and a trading market price of each share in the fund. It may help to picture these in baskets of about 50,000 shares for the creation/redemption process. If the NAV is greater than the market price, then arbitrageurs will buy up shares at the market price and do an \\\"\\\"in-kind\\\"\\\" transaction that will be worth the NAV value that the arbitrageurs could turn around and sell for an immediate profit. If the market price is greater than the NAV, then the arbitrageurs will buy up the underlying securities that can be exchanged \\\"\\\"in-kind\\\"\\\" for shares in the fund that can then be sold on the market for an immediate profit. What is the ETF Creation/Redemption Mechanism? would be a source on this though I imagine there are others. Now, in the case of VXX, there is something to be said for how much trading is being done and what impact this can have. From a July 8, 2013 Yahoo Finance article: At big option trade in the iPath S&P 500 VIX Short-Term Futures Note is looking for another jump in volatility. More than 250,000 VXX options have already traded, twice its daily average over the last month. optionMONSTER systems show that a trader bought 13,298 August 26 calls for the ask price of $0.24 in volume that was 6 times the strike's previous open interest, clearly indicating new activity. Now the total returns of the ETF are a combination of changes in share price plus what happens with the distributions which could be held as cash or reinvested to purchase more shares.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"349668\",\n \"text\": \"This is more than likely a thing about your financial institution and the exchanges where they trade shares. Some exchanges cannot/will not handle odd lot transactions. Most established brokerages have software and accounting systems that will deal in round lots with the exchanges, but can track your shares individually. Sometimes specific stocks cannot be purchased in odd lots due to circumstances specific to that stock (trading only on a specific exchange, for example). Most brokerages offer dollar-cost averaging programs, but may limit which stocks are eligible, due to odd lot and partial share purchases. Check with your brokerage to see if they can support odd lot and/or DCA purchases. You may find another similar ETF with similar holdings that has better trading conditions, or might consider an open-end mutual fund with similar objectives. Mutual funds allow partial share purchases (you have $100 to invest today, and they issue you 35.2 shares, for example).\",\n \"title\": \"\"\n },\n {\n \"docid\": \"472663\",\n \"text\": \"\\\"An Exchange-Traded Fund (ETF) is a special type of mutual fund that is traded on the stock exchange like a stock. To invest, you buy it through a stock broker, just as you would if you were buying an individual stock. When looking at a mutual fund based in the U.S., the easiest way to tell whether or not it is an ETF is by looking at the ticker symbol. Traditional mutual funds have ticker symbols that end in \\\"\\\"X\\\"\\\", and ETFs have ticker symbols that do not end in \\\"\\\"X\\\"\\\". The JPMorgan Emerging Markets Equity Fund, with ticker symbol JFAMX, is a traditional mutual fund, not an ETF. JPMorgan does have ETFs; the JPMorgan Diversified Return Emerging Markets Equity ETF, with ticker symbol JPEM, is an example. This ETF invests in similar stocks as JFAMX; however, because it is an index-based fund instead of an actively managed fund, it has lower fees. If you aren't sure about the ticker symbol, the advertising/prospectus of any ETF should clearly state that it is an ETF. (In the example of JPEM above, they put \\\"\\\"ETF\\\"\\\" right in the fund name.) If you don't see ETF mentioned, it is most likely a traditional mutual fund. Another way to tell is by looking at the \\\"\\\"investment minimums\\\"\\\" of the fund. JFAMX has a minimum initial investment of $1000. ETFs, however, do not have an investment minimum listed; because it is traded like a stock, you simply buy whole shares at whatever the current share price is. So if you look at the \\\"\\\"Fees and Investment Minimums\\\"\\\" section of the JPEM page, you'll see the fees listed, but not any investment minimums.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"367960\",\n \"text\": \"\\\"I think you are asking about actively managed funds vs. indexes and possibly also vs. diversified funds like target date funds. This is also related to the question of mutual fund vs. ETF. First, a fund can be either actively managed or it can attempt to track an index. An actively managed fund has a fund manager who tries to find the best stocks to invest in within some constraints, like \\\"\\\"this fund invests in large cap US companies\\\"\\\". An index fund tries to match as closely as possible the performance of an index like the S&P 500. A fund may also try to offer a portfolio that is suitable for someone to put their entire account into. For example, a target date fund is a fund that may invest in a mix of stocks, bonds and foreign stock in a proportion that would be appropriate to someone expecting to retire in a certain year. These are not what people tend to think of as the canonical examples of mutual funds, even though they share the same legal structure and investment mechanisms. Secondly, a fund can either be a traditional mutual fund or it can be an exchange traded fund (ETF). To invest in a traditional mutual fund, you send money to the fund, and they give you a number of shares equal to what that money would have bought of the net asset value (NAV) of the fund at the end of trading on the day they receive your deposit, possibly minus a sales charge. To invest in an ETF, you buy shares of the ETF on the stock market like any other stock. Under the covers, an ETF does have something similar to the mechanism of depositing money to get shares, but only big traders can use that, and it's not used for investing, but only for people who are making a market in the stock (if lots of people are buying VTI, Big Dealer Co will get 100,000 shares from Vanguard so that they can sell them on the market the next day). Historically and traditionally, ETFs are associated with an indexing strategy, while if not specifically mentioned, people assume that traditional mutual funds are actively managed. Many ETFs, notably all the Vanguard ETFs, are actually just a different way to hold the same underlying fund. The best way to understand this is to read the prospectus for a mutual fund and an ETF. It's all there in reasonably plain English.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"531180\",\n \"text\": \"You can look into specific market targeted mutual funds or ETF's. For Norway, for example, look at NORW. If you want to purchase specific stocks, then you'd better be ready to trade on local stock exchanges in local currency. ETrade allows trading on some of the international stock exchanges (in Asia they have Hong Kong and Japan, in Europe they have the UK, Germany and France, and in the Americas they have the US and Canada). Some of the companies you're interested in might be trading there.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"39265\",\n \"text\": \"In addition to the higher risk as pointed out by @JamesRoth, you also need to consider that there are regulations against 'naked shorting' so you generally need to either own the security, or have someone that is willing to 'loan' the security to you in order to sell short. If you own a stock you are shorting, the IRS could view the transaction as a Sell followed by a buy taking place in a less than 30 day period and you could be subject to wash-sale rules. This added complexity (most often the finding of someone to loan you the security you are shorting) is another reason such trades are considered more advanced. You should also be aware that there are currently a number of proposals to re-instate the 'uptick rule' or some circuit-breaker variant. Designed to prevent short-sellers from driving down the price of a stock (and conducting 'bear raids etc) the first requires that a stock trade at the same or higher price as prior trades before you can submit a short. In the latter shorting would be prohibited after a stock price had fallen a given percentage in a given amount of time. In either case, should such a rule be (re)established then you could face limitations attempting to execute a short which you would not need to worry about doing simple buys or sells. As to vehicles that would do this kind of thing (if you are convinced we are in a bear market and willing to take the risk) there are a number of ETF's classified as 'Inverse Exchange Traded Funds (ETF's) for a variety of markets that via various means seek to deliver a return similar to that of 'shorting the market' in question. One such example for a common broad market is ticker SH the ProShares Short S&P500 ETF, which seeks to deliver a return that is the inverse of the S&P500 (and as would be predicted based on the roughly +15% performance of the S&P500 over the last 12 months, SH is down roughly -15% over the same period). The Wikipedia article on inverse ETF's lists a number of other such funds covering various markets. I think it should be noted that using such a vehicle is a pretty 'aggressive bet' to take in reaction to the belief that a bear market is imminent. A more conservative approach would be to simply take money out of the market and place it in something like CD's or Treasury instruments. In that case, you preserve your capital, regardless of what happens in the market. Using an inverse ETF OTOH means that if the market went bull instead of bear, you would lose money instead of merely holding your position.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"369266\",\n \"text\": \"A stock, bond or ETF is basically a commodity. Where you bought it does not really matter, and it has a value in USD only inasmuch as there is a current market price quoted at an American exchange. But nothing prevents you from turning around and selling it on a European exchange where it is also listed for an equivalent amount of EUR (arbitrage activities of investment banks ensure that the price will be equivalent in regard to the current exchange rate). In fact, this can be used as a cheap form of currency conversion. For blue chips at least this is trivial; exotic securities might not be listed in Europe. All you need is a broker who allows you to trade on European exchanges and hold an account denominated in EUR. If necessary, transfer your securities to a broker who does, which should not cost more than a nominal fee. Mutual funds are a different beast though; it might be possible to sell shares on an exchange anyway, or sell them back to the issuer for EUR. It depends. In any case, however, transferring 7 figure sums internationally can trigger all kinds of tax events and money laundering investigations. You really need to hire a financial advisor who has international investment experience for this kind of thing, not ask a web forum!\",\n \"title\": \"\"\n },\n {\n \"docid\": \"65663\",\n \"text\": \"\\\"@sdg's answer is spot-on with the advice to avoid repeated conversions, but I'd like to provide some specifics on the fees involved: Each time you round-trip Canadian dollars (CAD) through a U.S.-dollar (USD) priced security at TD Waterhouse and leave your proceeds in CAD, you're paying a total foreign exchange fee – implied in their rate spread – of about 3%, give or take. That's ~3% per buy & sell combination, or ~1.5% on each end. You can imagine if you trade back & forth frequently, you can quickly lose a lot of money. Do it back and forth ten times in a year and you're out ~30% on the fees alone! The TD U.S. Money Market Fund (TDB166) that TD Waterhouse is referring to has no direct commission to buy or sell, but it does have a Management Expense Ratio (MER) of 0.20% per year – basically a fee which is deducted from the fund's returns (which, today, are also close to zero.) Practically speaking, that's a very slim fee to hold some USD in your Canadian dollar TFSA. While 0.20% is cheap, a point to keep in mind is if you maintain a significant USD balance, you are maintaining currency risk: You can lose money in CAD terms if the CAD appreciates vs. USD. Additional references: Canadian Capitalist describes TD Waterhouse and the use of TDB166 and \\\"\\\"wash trades\\\"\\\" at How to \\\"\\\"Wash\\\"\\\" Your Trade? He's referring to RRSPs, but the same applies to TFSAs, which came out after the post was written. Canadian Couch Potato has two relevant articles: Are US-listed ETFs Really Cheaper? and Lowering Your Currency Exchange Fees.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"84800\",\n \"text\": \"\\\"Your broker, Ameritrade, offers a variety of Exchange Traded Funds (ETFs) that you can buy and sell with zero commission. An ETF is like a mutual fund, but you buy and sell shares the same way you buy and sell shares of stocks. From your point of view, the relevance of this is that you can buy and sell as many or as few shares as you like, even down to a single share. Note that to get the commission-free trades on the available ETFs you have to sign up for it in your account profile. Be sure to do that before you enter any buy orders. You'll want to start by looking at the Ameritrade's list of commission-free ETFs. Notice that they are divided into different categories: stocks, bonds, international, and commodities. Which categories you pick from will depend on your personal investing goals, time horizon, risk tolerance, and so on. There are lots of questions and answers on this site that talk about asset allocation. You should read them, as it is the most important decision you will make with your portfolio. The other thing you want to be aware of is the expense ratio for each fund. These expenses reduce the fund's return (they are included in the calculation of the net asset value of the shares), so lower is definitely better. Personally, I wouldn't even consider paying more than about 0.10% (commonly read \\\"\\\"10 basis points\\\"\\\" or \\\"\\\"10 bp\\\"\\\") for a broad-based domestic stock fund. For a sectoral fund you might put up with as much as 20 bp in expenses. Bond funds tend to be a little more expensive, so maybe allow as much as 25 bp, and likewise for international funds. I've never invested in commodity funds, so I'll let someone else opine on appropriate expense ratios for those. Once you've decided what funds you want (and have signed up for commission-free trades), all you have to do is enter the trade orders. The website where you manage your account has tutorials on how to do that. After that you should be all set. Good luck with your investing!\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"224765\",\n \"text\": \"\\\"An ETF does not track any one individual stock. It \\\"\\\"is a marketable security that tracks an index, a commodity, bonds, or a basket of assets like an index fund.\\\"\\\" Check out this link to learn more about ETFs. The easiest way see what ETF tracks a stock is to determine what sector and industry that company is in and find some ETF that trade it. The ETF will likely trade that stock, assuming that its market cap and exchange it trades on fits within the parameters of the ETF.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"151203\",\n \"text\": \"A derivative in finance is simply any asset whose value is based on the value of another asset or based on the value of a group of assets. A derivative contract is a type of contract (usually a 'standardized contract') with specific payout instruction based on the price changes of a different asset. The basic idea is that it becomes easier to make a claim to an asset or property (and profit from this claim), without needing to physically transfer it (or even the title to said asset), and use much less capital to do so (reduce risk). They become problematic when multiple people may have claims to the real asset, or when the value of the derivatives changes very quickly or are hard to calculate. There are also liquidity problems the further you get from the real asset. This is not a problem for all kinds of derivatives contracts. And you must recognize that derivatives are used colloquially in a way that has nothing to do with reality to cause fear in people/investors that are not financially savvy. Many derivatives also have dubious or no economic purposes such that regulators don't allow them to be traded since they can't see how it is different from gambling. This is seen in financial markets that are less liberalized or cultures with puritanical backgrounds. Typically the trick is to convince regulators that the derivative or financial product helps with reducing risk and hedging and it will get approved. I've mentioned some terminology, but this depends specifically on what kind of derivatives contract you become interested in. Swaps, Credit Default Swaps, Futures, Options, Options on Futures, Leveraged Exchange Traded Funds, Inverse Leveraged Exchange Traded Funds, warrants, and more all have their own terminology. How to trade them in a simulation? It all depends on which financial product you really become interested in.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"276983\",\n \"text\": \"You haven't looked very far if you didn't find index tracking exchange-traded funds (ETFs) on the Toronto Stock Exchange. There are at least a half dozen major exchange-traded fund families that I'm aware of, including Canadian-listed offerings from some of the larger ETF providers from the U.S. The Toronto Stock Exchange (TSX) maintains a list of ETF providers that have products listed on the TSX.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"515643\",\n \"text\": \"So, couple of things. Firstly, every international ETF includes risk disclosure language in the prospectus covering both market disruption events as well as geopolitical risk, so the sponsor would be pretty well insulated from direct liability for anything. If the Russian market were truly shut down there are true-up mechanisms in place but in the scenario you're describing the market is still open, it's just only a few participants can trade in it. First thing to do is shut down creates- that is, allow no new money to come into the fund. This at least prevents your problem from getting bigger. Second you're going to switch all redemptions to in kind only. MV itself can't trade in the underlying so they're kind of jammed here. An ETF sponsor can't really refuse your redemption request (can delay, but only for a short time), but they can control the form in which they respond to it. What theoretically should happen here is an AP not subject to sanctions will step in and handle redemptions. Issue is, they'll probably charge for this so you should expect the fund to start trading at a discount to NAV (you, as an investor, sell to them cheaply, they submit a redemption request, then sell the stocks locally). Someone else has pointed that market makers will start stat arbing the fund using correlated/substitute instruments, which totally will help keep things in line, but my guess is that you'd still see the name trading away from NAV regardless. Driver of this will be the amount of money desperate to get out - if investors are content to wait the sanctions out who knows.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"205280\",\n \"text\": \"\\\"According to what little information is available currently, this fund is most akin to an actively managed exchange traded fund rather than an investment trust. An investment trust is an actively managed, closed-end fund that is tradeable on the stock market. \\\"\\\"Closed-end\\\"\\\" means that there are a fixed number of shares available for trading, so if you wish to buy or sell shares in a closed-end fund you need to find someone willing to sell or buy shares. \\\"\\\"Actively managed\\\"\\\" means that the assets are selected by the fund managers in the belief that they will perform well. This is in contrast to a \\\"\\\"passively managed\\\"\\\" fund which simply tracks an underlying index. The closed-end nature of investment trusts means that the share price is not well correlated to the value of the underlying assets. Indeed, almost all UK investment trusts trade at a significant discount to their net asset value. This reflects their historic poor performance and relatively weak liquidity. Of course there are some exceptions to this. Examples of open-end funds are unit trust (US = mutual funds) and ETFs (exchange traded funds). They are \\\"\\\"open-end\\\"\\\" funds in the sense that the number of shares/units available will change according to demand. Most importantly, the price of a share/unit will be strongly correlated to the net asset value of the underlying portfolio. In general, for an open-end fund, if the net asset value of the fund is X and there are Y shares/units outstanding, then the price of a share/unit will be X/Y. Historic data shows that passively managed funds (index trackers) \\\"\\\"always\\\"\\\" outperform actively managed funds in the long term. One of the big issues with actively managed funds is they have relatively high management fees. The Peoples Trust will be charging about 1% with a promise that this should come down over time. Compare this to a fee of 0.05% on a large, major market index tracking ETF. Further, the 1% headline fee being touted by Peoples Trust is a somewhat misleading, since they are paying their employees bonuses with shares in the fund. This will cause dilution of the net asset value per share and can be read as addition management fees by proxy. Since competent fund managers will demand high incomes, bonus shares could easily double the management fees, depending on the size of the fund. In summary, history has shown that the promises of active fund managers rarely (if ever) come to fruition. Personally, I would not consider this to be an attractive investment and would look more towards a passively managed major market index ETF with low management fees.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"479420\",\n \"text\": \"Mutual funds buy (and sell) shares in companies in accordance with the policies set forth in their prospectus, not according to the individual needs of an investor, that is, when you invest money in (or withdraw money from) a mutual fund, the manager buys or sells whatever shares that, in the manager's judgement, will be the most appropriate ones (consistent with the investment policies). Thus, a large-cap mutual fund manager will not buy the latest hot small-cap stock that will likely be hugely profitable; he/she must choose only between various large capitalization companies. Some exchange-traded funds are fixed baskets of stocks. Suppose you will not invest in a company X as a matter of principle. Unless a mutual fund prospectus says that it will not invest in X, you may well end up having an investment in X at some time because the fund manager bought shares in X. With such an ETF, you know what is in the basket, and if the basket does not include stock in X now, it will not own stock in X at a later date. Some exchange-traded funds are constructed based on some index and track the index as a matter of policy. Thus, you will not be investing in X unless X becomes part of the index because Standard or Poor or Russell or somebody changed their minds, and the ETF buys X in order to track the index. Finally, some ETFs are exactly like general mutual funds except that you can buy or sell ETF shares at any time at the price at the instant that your order is executed whereas with mutual funds, the price of the mutual fund shares that you have bought or sold is the NAV of the mutual fund shares for that day, which is established based on the closing prices at the end of the trading day of the stocks, bonds etc that the fund owns. So, you might end up owning stock in X at any time based on what the fund manager thinks about X.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"322725\",\n \"text\": \"In the past 10 years there have been mutual funds that would act as a single bucket of stocks and bonds. A good example is Fidelity's Four In One. The trade off was a management fee for the fund in exchange for having to manage the portfolio itself and pay separate commissions and fees. These days though it is very simple and pretty cheap to put together a basket of 5-6 ETFs that would represent a balanced portfolio. Whats even more interesting is that large online brokerage houses are starting to offer commission free trading of a number of ETFs, as long as they are not day traded and are held for a period similar to NTF mutual funds. I think you could easily put together a basket of 5-6 ETFs to trade on Fidelity or TD Ameritrade commission free, and one that would represent a nice diversified portfolio. The main advantage is that you are not giving money to the fund manager but rather paying the minimal cost of investing in an index ETF. Overall this can save you an extra .5-1% annually on your portfolio, just in fees. Here are links to commission free ETF trading on Fidelity and TD Ameritrade.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"328699\",\n \"text\": \"\\\"The London Stock Exchange offers a wealth of exchange traded products whose variety matches those offered in the US. Here is a link to a list of exchange traded products listed on the LSE. The link will take you to the list of Vanguard offerings. To view those offered by other managers, click on the letter choices at the top of the page. For example, to view the iShares offerings, click on \\\"\\\"I\\\"\\\". In the case of Vanguard, the LSE listed S&P500 ETF is traded under the code VUSA. Similarly, the Vanguard All World ETF trades under the code VWRL. You will need to be patient viewing iShares offerings since there are over ten pages of them, and their description is given by the abbreviation \\\"\\\"ISH name\\\"\\\". Almost all of these funds are traded in GBP. Some offer both currency hedged and currency unhedged versions. Obviously, with the unhedged version you are taking on additional currency risk, so if you wish to avoid currency risk then choose a currency hedged version. Vanguard does not appear to offer currency hedged products in London while iShares does. Here is a list of iShares currency hedged products. As you can see, the S&P500 currency hedged trades under the code IGUS while the unhedged version trades under the code IUSA. The effects of BREXIT on UK markets and currency are a matter of opinion and difficult to quantify currently. The doom and gloom warnings of some do not appear to have materialised, however the potential for near-term volatility remains so longs as the exit agreement is not formalised. In the long-term, I personally believe that BREXIT will, on balance, be a positive for the UK, but that is just my opinion.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"454224\",\n \"text\": \"A mutual fund has several classes of shares that are charged different fees. Some shares are sold through brokers and carry a sales charge (called load) that compensates the broker in lieu of a fee that the broker would charge the client for the service. Vanguard does not have sales charge on its funds and you don't need to go through a broker to buy its shares; you can buy directly from them. Admiral shares of Vanguard funds are charged lower annual expenses than regular shares (yes, all mutual funds charge expenses for fund adninistration that reduce the return that you get, and Vanguard has some of the lowest expense ratios) but Admiral shares are available only for large investments, typically $50K or so. If you have invested in a Vanguard mutual fund, your shares can be set to automatically convert to Admiral shares when the investment reaches the right level. A mutual fund manager can buy and sell stocks to achieve the objectives of the fund, so what stockes you are invested in as a share holder in a mutual fund will typically be unknown to you on a day-to-day basis. On the other hand, Exchange-traded funds (ETFs) are fixed baskets of stocks, and you can buy shares in the ETF. These shares are bought and sold through a broker (so you pay a transaction fee each time) but expenses are lower since there is no manager to buy and sell stocks: the basket is fixed. Many ETFs follow specific market indexes (e.g. S&P 500). Another difference between ETFs and mutual funds is that you can buy and sell ETFs at any time of the day just as if you could if you held stocks. With mutual funds, any buy and sell requests made during the day are processed at the end of the day and the value of the shares that you buy or sell is determined by the closing price of the stocks held by the mutual fund. With ETFs, you are getting the intra-day price at the time the buy or sell order is executed by your broker.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"183898\",\n \"text\": \"It is true that this is possible, however, it's very remote in the case of the large and reputable fund companies such as Vanguard. FDIC insurance protects against precisely this for bank accounts, but mutual funds and ETFs do not have an equivalent to FDIC insurance. One thing that does help you in the case of a mutual fund or ETF is that you indirectly (through the fund) own actual assets. In a cash account at a bank, you have a promise from the bank to pay, and then the bank can go off and use your money to make loans. You don't in any sense own the bank's loans. With a fund, the fund company cannot (legally) take your money out of the fund, except to pay the expense ratio. They have to use your money to buy stocks, bonds, or whatever the fund invests in. Those assets are then owned by the fund. Legally, a mutual fund is a special kind of company defined in the Investment Company Act of 1940, and is a separate company from the investment advisor (such as Vanguard): http://www.sec.gov/answers/mfinvco.htm Funds have their own boards, and in principle a fund board can even fire the company advising the fund, though this is not likely since boards aren't usually independent. (a quick google found this article for more, maybe someone can find a better one: http://www.marketwatch.com/story/mutual-fund-independent-board-rule-all-but-dead) If Vanguard goes under, the funds could continue to exist and get a new adviser, or could be liquidated with investors receiving whatever the assets are worth. Of course, all this legal stuff doesn't help you with outright fraud. If a fund's adviser says it bought the S&P 500, but really some guy bought himself a yacht, Madoff-style, then you have a problem. But a huge well-known ETF has auditors, tons of different employees, lots of brokerage and exchange traffic, etc. so to me at least it's tough to imagine a risk here. With a small fund company with just a few people - and there are lots of these! - then there's more risk, and you'd want to carefully look at what independent agent holds their assets, who their auditors are, and so forth. With regular mutual funds (not ETFs) there are more issues with diversifying across fund companies: With ETFs, there probably isn't much downside to diversifying since you could buy them all from one brokerage account. Maybe it even happens naturally if you pick the best ETFs you can find. Personally, I would just pick the best ETFs and not worry about advisor diversity. Update: maybe also deserving a mention are exchange-traded notes (ETNs). An ETN's legal structure is more like the bank account, minus the FDIC insurance of course. It's an IOU from the company that runs the ETN, where they promise to pay back the value of some index. There's no investment company as with a fund, and therefore you don't own a share of any actual assets. If the ETN's sponsor went bankrupt, you would indeed have a problem, much more so than if an ETF's sponsor went bankrupt.\",\n \"title\": \"\"\n }\n]"}}},{"rowIdx":195,"cells":{"query_id":{"kind":"string","value":"PLAIN-1513"},"query":{"kind":"string","value":"lima beans"},"positive_passages":{"kind":"list like","value":[{"docid":"MED-4509","text":"Hypercholesterolemia is a major modifiable risk factor for cardiovascular disease. Some, but not all, studies have shown that soy protein intake decreases total and low-density lipoprotein cholesterol and triglycerides and increases high-density lipoprotein cholesterol. The objective of this meta-analysis was to examine the effect of soy protein supplementation on serum lipid levels in adults. English language articles were retrieved by searching MEDLINE (1966 to February 2005) and the bibliographies of the retrieved articles. A total of 41 randomized controlled trials in which isolated soy protein supplementation was the only intervention and the net changes in serum lipids during intervention were reported. Information on study design, sample size, participant characteristics, intervention, follow-up duration, and treatment outcomes was independently abstracted using a standardized protocol. Using a random-effects model, data from each study were pooled and weighted by the inverse of their variance. Soy protein supplementation was associated with a significant reduction in mean serum total cholesterol (-5.26 mg/dl, 95% confidence interval [CI] -7.14 to -3.38), low-density lipoprotein cholesterol (-4.25 mg/dl, 95% CI -6.00 to -2.50), and triglycerides (-6.26 mg/dl, 95% CI -9.14 to -3.38) and a significant increase in high-density lipoprotein cholesterol (0.77 mg/dl, 95% CI 0.20 to 1.34). Meta-regression analyses showed a dose-response relation between soy protein and isoflavone supplementation and net changes in serum lipids. These results indicate that soy protein supplementation reduces serum lipids among adults with or without hypercholesterolemia. In conclusion, replacing foods high in saturated fat, trans-saturated fat, and cholesterol with soy protein may have a beneficial effect on coronary risk factors.","title":"A meta-analysis of the effect of soy protein supplementation on serum lipids."},{"docid":"MED-4510","text":"Background and Aims Studies evaluating the effect of legume consumption on cholesterol have focused on soybeans, however non-soy legumes, such as a variety of beans, peas, and some seeds, are commonly consumed in Western countries. We conducted a meta-analysis of randomized controlled trials evaluating the effects of non-soy legume consumption on blood lipids. Methods and Results Studies were retrieved by searching MEDLINE (from January 1966 through July 2009), EMBASE (from January 1980 to July 2009), and the Cochrane Collaboration's Central Register of Controlled Clinical Trials using the following terms as medical subject headings and keywords: fabaceae not soybeans not isoflavones and diet or dietary fiber and cholesterol or hypercholesterolemia or triglycerides or cardiovascular diseases. Bibliographies of all retrieved articles were also searched. From 140 relevant reports, 10 randomized clinical trials were selected which compared a non-soy legume diet to control, had a minimum duration of 3 weeks, and reported blood lipid changes during intervention and control. Data on sample size, participant characteristics, study design, intervention methods, duration, and treatment results were independently abstracted by 2 investigators using a standardized protocol. Data from 10 trials representing 268 participants were examined using a random-effects model. Pooled mean net change in total cholesterol for those treated with a legume diet compared to control was −11.8 mg/dL (95% confidence interval [CI], −16.1 to −7.5); mean net change in low density lipoprotein cholesterol was −8.0 mg/dL (95% CI, −11.4 to −4.6). Conclusion These results indicate that a diet rich in legumes other than soy decreases total and LDL cholesterol.","title":"Non-Soy Legume Consumption Lowers Cholesterol Levels: A Meta-Analysis of Randomized Controlled Trials"}],"string":"[\n {\n \"docid\": \"MED-4509\",\n \"text\": \"Hypercholesterolemia is a major modifiable risk factor for cardiovascular disease. Some, but not all, studies have shown that soy protein intake decreases total and low-density lipoprotein cholesterol and triglycerides and increases high-density lipoprotein cholesterol. The objective of this meta-analysis was to examine the effect of soy protein supplementation on serum lipid levels in adults. English language articles were retrieved by searching MEDLINE (1966 to February 2005) and the bibliographies of the retrieved articles. A total of 41 randomized controlled trials in which isolated soy protein supplementation was the only intervention and the net changes in serum lipids during intervention were reported. Information on study design, sample size, participant characteristics, intervention, follow-up duration, and treatment outcomes was independently abstracted using a standardized protocol. Using a random-effects model, data from each study were pooled and weighted by the inverse of their variance. Soy protein supplementation was associated with a significant reduction in mean serum total cholesterol (-5.26 mg/dl, 95% confidence interval [CI] -7.14 to -3.38), low-density lipoprotein cholesterol (-4.25 mg/dl, 95% CI -6.00 to -2.50), and triglycerides (-6.26 mg/dl, 95% CI -9.14 to -3.38) and a significant increase in high-density lipoprotein cholesterol (0.77 mg/dl, 95% CI 0.20 to 1.34). Meta-regression analyses showed a dose-response relation between soy protein and isoflavone supplementation and net changes in serum lipids. These results indicate that soy protein supplementation reduces serum lipids among adults with or without hypercholesterolemia. In conclusion, replacing foods high in saturated fat, trans-saturated fat, and cholesterol with soy protein may have a beneficial effect on coronary risk factors.\",\n \"title\": \"A meta-analysis of the effect of soy protein supplementation on serum lipids.\"\n },\n {\n \"docid\": \"MED-4510\",\n \"text\": \"Background and Aims Studies evaluating the effect of legume consumption on cholesterol have focused on soybeans, however non-soy legumes, such as a variety of beans, peas, and some seeds, are commonly consumed in Western countries. We conducted a meta-analysis of randomized controlled trials evaluating the effects of non-soy legume consumption on blood lipids. Methods and Results Studies were retrieved by searching MEDLINE (from January 1966 through July 2009), EMBASE (from January 1980 to July 2009), and the Cochrane Collaboration's Central Register of Controlled Clinical Trials using the following terms as medical subject headings and keywords: fabaceae not soybeans not isoflavones and diet or dietary fiber and cholesterol or hypercholesterolemia or triglycerides or cardiovascular diseases. Bibliographies of all retrieved articles were also searched. From 140 relevant reports, 10 randomized clinical trials were selected which compared a non-soy legume diet to control, had a minimum duration of 3 weeks, and reported blood lipid changes during intervention and control. Data on sample size, participant characteristics, study design, intervention methods, duration, and treatment results were independently abstracted by 2 investigators using a standardized protocol. Data from 10 trials representing 268 participants were examined using a random-effects model. Pooled mean net change in total cholesterol for those treated with a legume diet compared to control was −11.8 mg/dL (95% confidence interval [CI], −16.1 to −7.5); mean net change in low density lipoprotein cholesterol was −8.0 mg/dL (95% CI, −11.4 to −4.6). Conclusion These results indicate that a diet rich in legumes other than soy decreases total and LDL cholesterol.\",\n \"title\": \"Non-Soy Legume Consumption Lowers Cholesterol Levels: A Meta-Analysis of Randomized Controlled Trials\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"MED-3170","text":"Background Few studies have focused on the cognitive morbidity of neurocysticercosis (NCC), one of the most common parasitic infections of the central nervous system. We longitudinally assessed the cognitive status and quality of life (QoL) of patients with incident symptomatic NCC cases and matched controls. Methodology/Principal Findings The setting of the study was the Sabogal Hospital and Cysticercosis Unit, Department of Transmissible Diseases, National Institute of Neurological Sciences, Lima, Peru. The design was a longitudinal study of new onset NCC cases and controls. Participants included a total of 14 patients with recently diagnosed NCC along with 14 healthy neighborhood controls and 7 recently diagnosed epilepsy controls. A standardized neuropsychological battery was performed at baseline and at 6 months on NCC cases and controls. A brain MRI was performed in patients with NCC at baseline and 6 months. Neuropsychological results were compared between NCC cases and controls at both time points. At baseline, patients with NCC had lower scores on attention tasks (p<0.04) compared with epilepsy controls but no significant differences compared to healthy controls. Six months after receiving anti-parasitic treatment, the NCC group significantly improved on tasks involving psychomotor speed (p<0.02). QoL at baseline suggested impaired mental function and social function in both the NCC and epilepsy group compared with healthy controls. QoL gains in social function (p = 0.006) were noted at 6 months in patients with NCC. Conclusions/Significance Newly diagnosed patients with NCC in this sample had mild cognitive deficits and more marked decreases in quality of life at baseline compared with controls. Improvements were found in both cognitive status and quality of life in patients with NCC after treatment. Author Summary Neurocysticercosis (NCC) is one of the most common parasitic infections of the central nervous system. Cognitive changes have been frequently reported with this disease but have not been well studied. Our study team recruited a group of new onset NCC cases and a matched set of healthy neighborhood controls and new onset epilepsy controls in Lima, Peru for this study. A neuropsychological battery was administered at baseline and at 6 months to all groups. Brain MRI studies were also obtained on NCC cases at baseline and at 6 months. Newly diagnosed patients with NCC had mild cognitive deficits and more marked decreases in quality of life at baseline compared with controls. Improvements were found in both cognitive status and quality of life in patients with NCC after treatment. This study is the first to assess cognitive status and quality of life longitudinally in patients with NCC and provides new data on an important clinical morbidity outcome.","title":"Cognitive Changes and Quality of Life in Neurocysticercosis: A Longitudinal Study"},{"docid":"MED-3584","text":"Background: A high intake of white rice is associated with the metabolic syndrome and type 2 diabetes. Costa Ricans follow a staple dietary pattern that includes white rice and beans, yet the combined role of these foods on cardiometabolic risk factors has not been studied. Objective: We aimed to determine the association between intake of white rice and beans and the metabolic syndrome and its components in Costa Rican adults (n = 1879) without diabetes. Design: Multivariate-adjusted means were calculated for components of the metabolic syndrome by daily servings of white rice and beans (<1, 1, or >1) and by the ratio of beans to white rice. The OR for the metabolic syndrome was calculated by substituting one serving of beans for one serving of white rice. Results: An increase in daily servings of white rice was positively associated with systolic blood pressure (BP), triglycerides, and fasting glucose and inversely associated with HDL cholesterol (P-trend <0.01 for all). An increase in servings of beans was inversely associated with diastolic BP (P = 0.049). Significant trends for higher HDL cholesterol and lower BP and triglycerides were observed for 1:3, 1:2, 1:1, and 2:1 ratios of beans to white rice. Substituting one serving of beans for one serving of white rice was associated with a 35% (95% CI: 15%, 50%) lower risk of the metabolic syndrome. Conclusion: Increasing the ratio of beans to white rice, or limiting the intake of white rice by substituting beans, may lower cardiometabolic risk factors.","title":"A higher ratio of beans to white rice is associated with lower cardiometabolic risk factors in Costa Rican adults"},{"docid":"MED-2140","text":"Background Around the world, beans and rice are commonly consumed together as a meal. With type 2 diabetes increasing, the effect of this traditional diet pattern on glycemic response has not been studied fully. Methods We evaluated the glycemic response of bean and rice traditional meals compared to rice alone in adults with type 2 diabetes. Seventeen men and women with type 2 diabetes controlled by metformin (n = 14) or diet/exercise (n = 3) aged 35–70 years participated in the randomized 4 × 4 crossover trial. The white long grain rice control, pinto beans/rice, black beans/rice, red kidney beans/rice test meals, matched for 50 grams of available carbohydrate, were consumed at breakfast after a 12 hour fast. Capillary blood glucose concentrations at baseline and at 30 minute intervals up to 180 minutes postprandial were collected. MANOVA for repeated measures established glucose differences between treatments. Paired t tests identified differences between bean types and the rice control following a significant MANOVA. Results Postprandial net glucose values were significantly lower for the three bean/rice treatments in contrast to the rice control at 90, 120 and 150 minutes. Incremental area under the curve values were significantly lower for the pinto and black bean/rice meals compared to rice alone, but not for kidney beans. Conclusions Pinto, dark red kidney and black beans with rice attenuate the glycemic response compared to rice alone. Promotion of traditional foods may provide non-pharmaceutical management of type 2 diabetes and improve dietary adherence with cultural groups. Trial registration Clinical Trials number NCT01241253","title":"Bean and rice meals reduce postprandial glycemic response in adults with type 2 diabetes: a cross-over study"},{"docid":"MED-4991","text":"BACKGROUND: Epidemiological studies have shown positive findings associated with legume consumption and measures of cardiovascular disease and obesity. However, few observational trials have examined beans as a separate food variable when determining associations with health parameters. OBJECTIVE: To determine the association of consuming beans on nutrient intakes and physiological parameters using the National Health and Examination Survey (NHANES) 1999-2002. METHODS: Using data from NHANES 1999-2002, a secondary analysis was completed with a reliable 24-hour dietary recall where three groups of bean consumers were identified (N = 1,475). We determined mean nutrient intakes and physiological values between bean consumers and non-consumers. Least square means, standard errors and ANOVA were calculated using appropriate sample weights following adjustment for age, gender, ethnicity and energy. RESULTS: Relative to non-consumers, bean consumers had higher intakes of dietary fiber, potassium, magnesium, iron, and copper (p's < 0.05). Those consuming beans had a lower body weight (p = 0.008) and a smaller waist size (p = 0.043) relative to non-consumers. Additionally, consumers of beans had a 23% reduced risk of increased waist size (p = 0.018) and a 22% reduced risk of being obese (p = 0.026). Also, baked bean consumption was associated with a lower systolic blood pressure. CONCLUSIONS: Bean consumers had better overall nutrient intake levels, better body weights and waist circumferences, and lower systolic blood pressure in comparison to non-consumers. These data support the benefits of bean consumption on improving nutrient intake and health parameters.","title":"Bean consumption is associated with greater nutrient intake, reduced systolic blood pressure, lower body weight, and a smaller waist circumference ..."},{"docid":"MED-3138","text":"Background Many consumers avoid eating beans because they believe legume consumption will cause excessive intestinal gas or flatulence. An increasing body of research and the 2010 Dietary Guidelines for Americans supports the benefits of a plant-based diet, and legumes specifically, in the reduction of chronic disease risks. The purpose of the current research was to investigate the perception of increased flatulence and gastrointestinal discomfort among participants who consumed a ½ cup of beans daily for 8 or 12 weeks. Methods Participants in three studies to test the effects of beans on heart disease biomarkers completed the same weekly questionnaire to assess gastrointestinal discomfort issues such as increased flatulence, stool changes, and bloating. Studies 1 and 2 were randomized crossover trials. Participants consumed ½ cup of pinto beans, black-eyed peas, and canned carrots as control (n = 17) in Study 1 for three randomized 8-week phases. For Study 2, participants ate ½ cup baked beans or canned carrots as control (n = 29) for two randomized 8-week phases. Study 3 was a parallel arm trial with 40 subjects receiving ½ cup pinto beans and 40 consuming a control soup for 12 weeks. Changes in the frequency of perceived flatulence, stool characteristics, and bloating were the primary outcome measures. Chi-square distributions were examined for the presence or absence of symptoms and demographic characteristics to determine differences by gender, age, body mass index (BMI), and bean type. Results Less than 50% reported increased flatulence from eating pinto or baked beans during the first week of each trial, but only 19% had a flatulence increase with black-eyed peas. A small percentage (3-11%) reported increased flatulence across the three studies even on control diets without flatulence-producing components. Conclusions People's concerns about excessive flatulence from eating beans may be exaggerated. Public health nutritionists should address the potential for gastrointestinal discomfort when increasing fiber intake from beans with clients. It is important to recognize there is individual variation in response to different bean types.","title":"Perceptions of flatulence from bean consumption among adults in 3 feeding studies"},{"docid":"MED-1880","text":"Legumes are the basés diet in several countries. They hold a high nutritional value, but other properties related to human health are nowadays being studied. The aim of this work was to study the influence of processes (boiling or germination) on the phenolic composition of dark beans (Phaseolus vulgaris L. c.v. Tolosana) and their effect on their antioxidant, neuroprotective and anticancer ability. Phenolic composition of raw and processed dark beans was analysed by HPLC-PAD and HPLC-ESI/MS. The antioxidant activity was evaluated by ORAC. Astrocytes cultures (U-373) have been used to test their neuroprotective effect. Anticancer activities were evaluated on three different cell lines (renal adenocarcinoma (TK-10), breast adenocarcinoma (MCF-7) and melanoma (UACC-62)) by sulphorhodamine B method. Qualitative and quantitative differences in phenolic composition have been observed between raw and processed dark beans that influence the antioxidant activity, mainly for germinated samples which show a decrease of antioxidant capacity. Although every assayed extracts decreased reactive oxygen species release and exhibited cytotoxicity activities on cancer cell lines, raw beans proved to be the most active in neuroprotective and antitumoral effects; this sample is especially rich in phenolic compounds, mainly anthocyanins. This study further demonstrated that phenolic composition of dark beans is related with cooking process and so with their neuroprotective and anticancer activity; cooking of dark beans improves their digestion and absorption at intestinal level, while maintaining its protective ability on oxidative process at cellular level. Copyright © 2012 Elsevier Ltd. All rights reserved.","title":"Effect of cooking and germination on phenolic composition and biological properties of dark beans (Phaseolus vulgaris L.)."},{"docid":"MED-3141","text":"OBJECTIVE: To evaluate the associations with chronic disease risk and mortality of the consequences of bean-free diets in Taiwanese adults with regard to gender. DESIGN: A sub-sample of the National Health Interview Survey (NHIS) in 2001 agreed to physical examination in the subsequent year. This group then took part in the Taiwanese Survey of Hyperglycaemia, Hyperlipidaemia and Hypertension (TwSHHH) in 2002. SETTING: Individual records were linked to the eventual death files from 2002 to 2008. SUBJECTS: Up to the end of 2008, a total of 2820 men and 2950 women were tracked by death registry over the 6·8 years of follow-up. RESULTS: Among 38,077 person-years, an average follow-up 6·5 years, 225 all-cause deaths were identified. Generalized linear models showed beans to be favourable for metabolic syndrome (other than for fasting glucose) in men; in women, beans were favourable for waist circumference and HbA1c. Cumulative logistic regression models for the effect of a bean-free diet on metabolic syndrome scores according to the Taiwanese-modified National Cholesterol Education Program-Adult Treatment Panel III (NCEP-tw) gave adjusted odds ratios of 1·83 in men and 1·45 in women. Cox regression models for the bean-free diet showed an increased hazard ratio for all-cause mortality among women (1·98, 95% CI 1·03, 3·81) but not men (1·28, 95% CI 0·76, 2·16). CONCLUSIONS: A bean-free diet may play a role in developing the metabolic syndrome in both genders, and is a significant predictor of all-cause mortality in Taiwanese women but not men.","title":"A bean-free diet increases the risk of all-cause mortality among Taiwanese women: the role of the metabolic syndrome."},{"docid":"MED-5079","text":"OBJECTIVE: To determine effects of daily intake of 1/2 cup pinto beans, black-eyed peas or carrots (placebo) on risk factors for coronary heart disease (CHD) and diabetes mellitus (DM) in free-living, mildly insulin resistant adults over an 8 week period. METHODS: Randomized, crossover 3x3 block design. Sixteen participants (7 men, 9 women) received each treatment for eight-weeks with two-week washouts. Fasting blood samples collected at beginning and end of periods were analyzed for total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol, triacylglycerols, high-sensitivity C-reactive protein, insulin, glucose, and hemoglobin A1c. RESULTS: A significant treatment-by-time effect impacted serum TC (p = 0.026) and LDL (p = 0.033) after eight weeks. Paired t-tests indicated that pinto beans were responsible for this effect (p = 0.003; p = 0.008). Mean change of serum TC for pinto bean, black-eyed pea and placebo were -19 +/- 5, 2.5 +/- 6, and 1 +/- 5 mg/dL, respectively (p = 0.011). Mean change of serum LDL-C for pinto bean, black-eyed pea and placebo were -14 +/- 4, 4 +/- 5, and 1 +/- 4 mg/dL, in that order (p = 0.013). Pinto beans differed significantly from placebo (p = 0.021). No significant differences were seen with other blood concentrations across the 3 treatment periods. CONCLUSIONS: Pinto bean intake should be encouraged to lower serum TC and LDL-C, thereby reducing risk for CHD.","title":"Pinto bean consumption reduces biomarkers for heart disease risk."},{"docid":"MED-2570","text":"The functional properties, including antioxidant and chemopreventative capacities as well as the inhibitory effects on angiotensin-converting enzyme (ACE), α-glucosidase and pancreatic lipase, of three Australian-grown faba bean genotypes (Nura, Rossa and TF(Ic*As)*483/13) were investigated using an array of in vitro assays. Chromatograms of on-line post column derivatisation assay coupled with HPLC revealed the existence of active phenolics (hump) in the coloured genotypes, which was lacking in the white-coloured breeding line, TF(Ic*As)*483/13. Roasting reduced the phenolic content, and diminished antioxidant activity by 10-40 % as measured by the reagent-based assays (diphenylpicrylhydrazyl, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) and oxygen radical absorbance capacity) in all genotypes. Cell culture-based antioxidant activity assay (cellular antioxidant activity) showed an increase of activity in the coloured genotypes after roasting. Faba bean extracts demonstrated cellular protection ability against H₂O₂-induced DNA damage (assessed using RAW264.7 cells), and inhibited the proliferation of all human cancer cell lines (BL13, AGS, Hep G2 and HT-29) evaluated. However, the effect of faba bean extracts on the non-transformed human cells (CCD-18Co) was negligible. Flow cytometric analyses showed that faba bean extracts successfully induced apoptosis of HL-60 (acute promyelocytic leukaemia) cells. The faba bean extracts also exhibited ACE, α-glucosidase and pancreatic lipase inhibitory activities. Overall, extracts from Nura (buff-coloured) and Rossa (red-coloured) were comparable, while TF(Ic*As)*483/13 (white-coloured) contained the lowest phenolic content and exhibited the least antioxidant and enzyme inhibition activities. These results are important to promote the utilisation of faba beans in human diets for various health benefits.","title":"In vitro investigations of the potential health benefits of Australian-grown faba beans (Vicia faba L.): chemopreventative capacity and inhibitory ..."},{"docid":"MED-3136","text":"The objective of this study was to determine the influence of frequent and long-term consumption of legume seeds on colonic function. Two groups of subjects were studied--one group habitually consumed legume seeds as part of their normal diet, a second group only infrequently consumed legumes. No differences between these groups could be detected for fecal output and frequency, intestinal transit time, VFA excretion or fecal pH during 23-day study periods in which subjects consumed either their usual diet or 100 g red kidney beans, daily. However, the addition of beans to the diets of both groups provided significantly more dietary fiber, and produced greater fecal output and a higher concentration of VFA in feces. Fecal output appeared to be determined by two independent parameters--dietary fiber intake and VFA excretion. Beans provided a physiologically useful source of dietary fiber and favorably influenced colonic function.","title":"Influence of frequent and long-term bean consumption on colonic function and fermentation."},{"docid":"MED-2147","text":"Consumption of Phaseolus vulgaris bean species such as pinto, black, navy or kidney may be beneficial in the prevention and treatment of chronic diseases. In particular, conditions that are promoted by increased glycaemic stress (hyperglycaemia and hyperinsulinaemia) including diabetes, CVD and cancer seem to be reduced in individuals who eat more of these beans. The present paper discusses the influence of P. vulgaris species on glycaemic response and the impact that relationship may have on the risk of developing diabetes, CVD and cancer.","title":"Phaseolus beans: impact on glycaemic response and chronic disease risk in human subjects."},{"docid":"MED-2580","text":"Adequate fruit and vegetable intake was suggested to protect against colorectal cancer and colorectal adenomas; however, several recent prospective studies reported no association. We examined the association between fruits and vegetables and adenomatous polyp recurrence in the Polyp Prevention Trial (PPT). The PPT was a low-fat, high-fiber, high-fruit, and vegetable dietary intervention trial of adenoma recurrence, in which there were no differences in the rate of adenoma recurrence in participants in the intervention and control arms of the trial. In this analysis of the entire PPT trial–based cohort, multiple logistic regression analysis was used to estimate the odds ratio (OR) of advanced and nonadvanced adenoma recurrence within quartiles of baseline and change (baseline minus the mean over 3 y) in fruit and vegetable intake, after adjustment for age, total energyy intake, use of nonsteroidal anti-inflammatory drugs, BMI, and gender. There were no significant associations between nonadvanced adenoma recurrence and overall change in fruit and vegetable consumption; however, those in the highest quartile of change in dry bean intake (greatest increase) compared with those in the lowest had a significantly reduced OR for advanced adenoma recurrence (OR = 0.35; 95% CI, 0.18–0.69; P for trend = 0.001). The median in the highest quartile of change in dry bean intake was 370% higher than the baseline intake. The PPT trial–based cohort provides evidence that dry beans may be inversely associated with advanced adenoma recurrence.","title":"High Dry Bean Intake and Reduced Risk of Advanced Colorectal Adenoma Recurrence among Participants in the Polyp Prevention Trial"},{"docid":"MED-2144","text":"Bean pods (Phaseolus vulgaris) are among the most widely used traditional remedies against diabetes mellitus. Historical knowledge is summarized and compared to recent study results. Reports dating from the first half of the 20(th) century as well as recent publications show contradictory results. It seems that Phaseolus preparations should not be considered the first choice in phytopharmaceutical treatment of diabetes or lead structure research. To be effective, fairly high doses of aqueous extracts need to be given. Because of their fiber content and an alpha-amylase inhibitory effect, beans might be more useful as food components in preventing or ameliorating type 2 diabetes.","title":"Beans and diabetes: Phaseolus vulgaris preparations as antihyperglycemic agents."},{"docid":"MED-2010","text":"Legumes (including alfalfa, clover, lupins, green beans and peas, peanuts, soybeans, dry beans, broad beans, dry peas, chickpeas, and lentils) represent an important component of the human diet in several areas of the world, especially in the developing countries, where they complement the lack of proteins from cereals, roots, and tubers. In some regions of the world, legume seeds are the only protein supply in the diet. The health benefits of legume consumption have received rising interest from researchers, and their consumption and production extends worldwide. Among European countries, higher legume consumption is observed around the Mediterranean, with per capita daily consumption between 8 and 23 g, while in Northern Europe, the daily consumption is less than 5 g per capita. The physiological effects of different legumes vary significantly. These differences may result from the polysaccharides composition, in particular, the quantity and variety of dietary fibers and starch, protein make-up, and variability in phytochemical content. The majority of legumes contain phytochemicals: bioactive compounds, including enzyme inhibitors, phytohemagglutinins (lectins), phytoestrogens, oligosaccharides, saponins, and phenolic compounds, which play metabolic roles in humans who frequently consume these foods. Dietary intake of phytochemicals may provide health benefits, protecting against numerous diseases or disorders, such as coronary heart disease, diabetes, high blood pressure and inflammation. The synergistic or antagonistic effects of these phytochemical mixtures from food legumes, their interaction with other components of the diet, and the mechanism of their action have remained a challenge with regard to understanding the role of phytochemicals in health and diseases. Their mitigating effects and the mechanism of their action need to be further addressed if we are to understand the role of phytochemicals in health and diseases. This review provides an overview of the nutritional quality of legumes and their potential contribution in cardiometabolic risk prevention.","title":"Nutritional quality of legumes, and their role in cardiometabolic risk prevention: a review."},{"docid":"MED-5078","text":"In this study, solid fermentation of steamed black soybean with various GRAS (Generally recognized as safe) filamentious-fungi including Aspergillus awamori, Aspergillus oryzae BCRC 30222, Aspergillus sojae BCRC 30103, Rhizopus azygosporus BCRC 31158 and Rhizopus sp. No. 2 was performed. Mutagenicity and antimutagenicity of the methanol extracts of unfermented and fermented steamed black soybeans against 4-nitroquinoline-N-oxide (4-NQO), a direct mutagen and Benzo[a]pyrene (B[a]P), an indirect mutagen, on Salmonella Typhimurium TA100 and TA 98, were examined. The methanol extracts of unfermented and fermented steamed black soybeans show no mutagenic activity for either test strains at the doses tested. The extracts inhibited mutagenesis by either 4-NQO or B[a]P in S. Typhimurium TA100 and TA98. Fermentation with fungi also enhanced the antimutagenic effect of black soybean while the antimutagenic effect of the fermented black soybeans extract varied with the starter organism, mutagen, and test strain of S. Typhimurium examined. Generally, the extracts of A. awamori-fermented black soybean exhibited the highest antimutagenic effect. With strain TA100, the inhibitory effects of 5.0 mg of A. awamori-fermented black soybean extract per plate on the mutagenic effects of 4-NQO and B[a]P were 92% and 89%, respectively, while the corresponding rates for extract of unfermented were 41% and 63%, respectively. With strain 98, the inhibition rates were 94 and 81% for the fermented bean extract and 58% and 44% for the unfermented bean extracts. Testing of extracts prepared from black soybean by A. awamori at temperatures 25, 30 and 35 degrees C and for times of 1-5 days revealed that, generally, the extract prepared from beans fermented at 30 degrees C for 3 days exhibited the greatest inhibition against the mutagenic effects of 4-NQO and B[a]P.","title":"Mutagenic and antimutagenic effects of methanol extracts of unfermented and fermented black soybeans."},{"docid":"MED-2141","text":"We investigated the association between dietary patterns and insulin resistance in the 3871 healthy Korean adults from the 2007 to 2008 Korea National Health and Nutrition Examination Survey. The whole grains and beans pattern was associated with lower prevalence of insulin resistance (OR for highest quintile=0.80, 95% CI=0.61-1.03, P for trend=0.013). Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.","title":"High intake of whole grains and beans pattern is inversely associated with insulin resistance in healthy Korean adult population."},{"docid":"MED-5080","text":"Bioactivity-guided fractionation of black bean (Phaseolus vulgaris) seed coats was used to determine the chemical identity of bioactive constituents, which showed potent antiproliferative and antioxidative activities. Twenty-four compounds including 12 triterpenoids, 7 flavonoids, and 5 other phytochemicals were isolated using gradient solvent fractionation, silica gel and ODS columns, and semipreparative and preparative HPLC. Their chemical structures were identified using MS, NMR, and X-ray diffraction analysis. Antiproliferative activities of isolated compounds against Caco-2 human colon cancer cells, HepG2 human liver cancer cells, and MCF-7 human breast cancer cells were evaluated. Among the compounds isolated, compounds 1, 2, 6, 7, 8, 13, 14, 15, 16, 19, and 20 showed potent inhibitory activities against the proliferation of HepG2 cells, with EC50 values of 238.8 +/- 19.2, 120.6 +/- 7.3, 94.4 +/- 3.4, 98.9 +/- 3.3, 32.1 +/- 6.3, 306.4 +/- 131.3, 156.9 +/- 11.8, 410.3 +/- 17.4, 435.9 +/- 47.7, 202.3 +/- 42.9, and 779.3 +/- 37.4 microM, respectively. Compounds 1, 2, 3, 5, 6, 7, 8, 9, 10, 11, 14, 15, 19, and 20 showed potent antiproliferative activities against Caco-2 cell growth, with EC50 values of 179.9 +/- 16.9, 128.8 +/- 11.6, 197.8 +/- 4.2, 105.9 +/- 4.7, 13.9 +/- 2.8, 35.1 +/- 2.9, 31.2 +/- 0.5, 71.1 +/- 11.9, 40.8 +/- 4.1, 55.7 +/- 8.1, 299.8 +/- 17.3, 533.3 +/- 126.0, 291.2 +/- 1.0, and 717.2 +/- 104.8 microM, respectively. Compounds 5, 7, 8, 9, 11, 19, 20 showed potent antiproliferative activities against MCF-7 cell growth in a dose-dependent manner, with EC50 values of 129.4 +/- 9.0, 79.5 +/- 1.0, 140.1 +/- 31.8, 119.0 +/- 7.2, 84.6 +/- 1.7, 186.6 +/- 21.1, and 1308 +/- 69.9 microM, respectively. Six flavonoids (compounds 14-19) showed potent antioxidant activity. These results showed the phytochemical extracts of black bean seed coats have potent antioxidant and antiproliferative activities.","title":"Phytochemicals of black bean seed coats: isolation, structure elucidation, and their antiproliferative and antioxidative activities."},{"docid":"MED-3132","text":"Little is known about dietitians current practice in counselling clients about the use of legumes in a low fat, high fibre diet. An exploratory e-mail questionnaire was sent to members of Dietitians of Canada to assess: dietitian use and preferences for legumes, dietitian practice, opinions about clients attitudes and preferences, and resource needs. Counsellors (n=256) had high personal use of legumes (64% > or = 1 serving/week) and frequently recommended legumes in counselling. The legumes most preferred by respondents and their clients were: peanuts, kidney beans, split peas, chickpeas, and lentils. Respondents often recommended canned bean products (76%) and tofu (61%), but other legume grocery products were less often recommended. The most common client issues identified were: flatulence (87% agreed), lack of familiarity (85%), and knowledge of preparation (82%). Dietitians were not satisfied with current resources to support practice, especially those respondents providing primarily clinical counselling services. The most requested resources were: recipes (90%), pamphlets (82%), food demonstrations (75%) and Internet sites (63%). Client level research is now needed to confirm the importance of the issues identified and to develop and test strategies for legume promotion in counselling.","title":"Legume promotion in counselling: an e-mail survey of dietitians."},{"docid":"MED-2085","text":"A diet rich in fruits and vegetables is known to decrease the risk of cardiovascular disease. However, the information regarding the antithrombotic activity (antiplatelet, anticoagulant, and fibrinolytic) of fruits and vegetables is scarce. The aim of this study was to assess the antithrombotic activity of extracts from fruits and vegetables widely consumed in central Chile. The study included samples of 19 fruits and 26 vegetables, representative of the local diet. The extracts prepared from each sample included an aqueous (juice or pressed solubles) and/or methanol-soluble fraction. The extracts were evaluated for antiplatelet, anticoagulant, and fibrinolytic activity in vitro at a final concentration of 1 mg/ml. The antiplatelet activity was assessed by platelet aggregation inhibition; anticoagulant activity was measured by the prothrombin time (PT), diluted prothrombin time (dPT), activated partial thromboplastin time (APTT), kaolin clotting time (KCT), and thrombin time. The fibrinolytic effect was determined with the euglobin clot lysis time and fibrin plate methods. Extracts of green beans and tomatoes inhibited platelet aggregation induced by ADP and arachidonic acid, in a concentration-dependent manner. The methanolic extracts of grapes prolonged the PT and dPT. Finally, extracts of raspberry prolonged the APTT and also presented fibrinolytic activity. In conclusion, from a screening that included a variety of fruits and vegetables, we found antiplatelet activity in green beans and tomatoes, anticoagulant activities in grapes and raspberries, whereas fibrinolytic activity was observed only in raspberries. Further investigations are necessary to advance in knowledge of the active compounds of these fruits and vegetables and their mechanisms of action.","title":"Antiplatelet, anticoagulant, and fibrinolytic activity in vitro of extracts from selected fruits and vegetables."},{"docid":"MED-5118","text":"OBJECTIVE: To compare the effects of two commercially available soy milks (one made using whole soy beans, the other using soy protein isolate) with low-fat dairy milk on plasma lipid, insulin, and glucose responses. DESIGN: Randomized clinical trial, cross-over design. SUBJECTS: Participants were 30-65 years of age, n = 28, with pre-study LDL-cholesterol (LDL-C) concentrations of 160-220 mg/dL, not on lipid lowering medications, and with an overall Framingham risk score of or=4 weeks. RESULTS: Mean LDL-C concentration at the end of each phase (+/- SD) was 161 +/- 20, 161 +/- 26 and 170 +/- 24 mg/dL for the whole bean soy milk, the soy protein isolate milk, and the dairy milk, respectively (p = 0.9 between soy milks, p = 0.02 for each soy milk vs. dairy milk). No significant differences by type of milk were observed for HDL-cholesterol, triacylglycerols, insulin, or glucose. CONCLUSION: A 25 g dose of daily soy protein from soy milk led to a modest 5% lowering of LDL-C relative to dairy milk among adults with elevated LDL-C. The effect did not differ by type of soy milk and neither soy milk significantly affected other lipid variables, insulin or glucose.","title":"Effect of two types of soy milk and dairy milk on plasma lipids in hypercholesterolemic adults: a randomized trial."},{"docid":"MED-3894","text":"The purpose of this study was to examine the effects of a natural carbohydrate (CHO) source in the form of sun-dried raisins (SDRs) vs. Sports Jelly Beans™ (SJBs) on endurance performance in trained cyclists and triathletes. Ten healthy men (18-33 years) completed 1 water-only acclimatization exercise trial and 2 randomized exercise trials administered in a crossover fashion. Each trial consisted of a 120-minute constant-intensity glycogen depletion period followed by a 10-km time trial (TT). During each experimental trial, participants consumed isocaloric amounts of SDRs or SJBs in 20-minute intervals. Measurements included time to complete 10-km TT, power output during 10-km TT, blood glucose levels and respiratory exchange ratio during glycogen depletion period, rate of perceived exertion (RPE), 'flow' questionnaire responses, and a hedonic (i.e., pleasantness) sensory acceptance test. There were no significant differences in endurance performance for TT time (SDRs vs. SJBs, 17.3 ± 0.4 vs. 17.3 ± 0.4 seconds) or power (229.3 ± 13.0 vs. 232.0 ± 13.6 W), resting blood glucose levels (5.8 ± 04 mmol·L(-1) for SDRs and 5.4 ± 0.2 mmol·L(-1) for SJBs), RPE, or flow experiences between SDR and SJB trials. However, the mean sensory acceptance scores were significantly higher for the SDRs compared to the SJBs (50.7 ± 1.7 vs. 44.3 ± 2.7). Consuming SDRs or SJBs during 120 minutes of intense cycling results in similar subsequent TT performances and are equally effective in maintaining blood glucose levels during exercise. Therefore, SDRs are a natural, pleasant, cost-effective CHO alternative to commercial SJBs that can be used during moderate- to high-intensity endurance exercise.","title":"Sun-dried raisins are a cost-effective alternative to Sports Jelly Beans in prolonged cycling."},{"docid":"MED-4869","text":"This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of various food additives, including flavouring agents, with a view to recommending acceptable daily intakes (ADIs) and to preparing specifications for identity and purity. The first part of the report contains a general discussion of the principles governing the toxicological evaluation and assessment of intake of food additives (in particular, flavouring agents). A summary follows of the Committee's evaluations of technical, toxicological and intake data for certain food additives (asparaginase from Aspergillus niger expressed in A. niger, calcium lignosulfonate (40-65), ethyl lauroyl arginate, paprika extract, phospholipase C expressed in Pichia pastoris, phytosterols, phytostanols and their esters, polydimethylsiloxane, steviol glycosides and sulfites [assessment of dietary exposure]) and 10 groups of related flavouring agents (aliphatic branched-chain saturated and unsaturated alcohols, aldehydes, acids and related esters; aliphatic linear alpha,beta-unsaturated aldehydes, acids and related alcohols, acetals and esters; aliphatic secondary alcohols, ketones and related esters; alkoxy-substituted allylbenzenes present in foods and essential oils and used as flavouring agents; esters of aliphatic acyclic primary alcohols with aliphatic linear saturated carboxylic acids; furan-substituted aliphatic hydrocarbons, alcohols, aldehydes, ketones, carboxylic acids and related esters, sulfides, disulfides and ethers; miscellaneous nitrogen-containing substances; monocyclic and bicyclic secondary alcohols, ketones and related esters; hydroxy- and alkoxy-substituted benzyl derivatives; and substances structurally related to menthol). Specifications for the following food additives were revised: canthaxanthin; carob bean gum and carob bean gum (clarified); chlorophyllin copper complexes, sodium and potassium salts; Fast Green FCF; guar gum and guar gum (clarified); iron oxides; isomalt; monomagnesium phosphate; Patent Blue V; Sunset Yellow FCF; and trisodium diphosphate. Re-evaluation of flavouring agents for which estimated intake was based on anticipated poundage data was carried out for 2-isopropyl- N,2,3-trimethylbutyramide (No. 1595) and L-monomenthyl glutarate (No. 1414). Annexed to the report are tables summarizing the Committee's recommendations for intakes and toxicological evaluations of the food additives considered.","title":"Evaluation of certain food additives."},{"docid":"MED-2150","text":"Previous investigations, of adolescent diet recalled in adulthood, found lower risk for benign breast disease (BBD) with higher intakes of vegetable fat and nuts during high school. We investigate whether vegetable protein and fat, derived from diets reported during pre-adolescence and adolescence, are associated with subsequent risk for BBD in young women. The Growing Up Today Study includes 9,039 females, 9–15 years in 1996, who completed questionnaires annually through 2001, and then in 2003, 2005, 2007, and 2010. Food frequency questionnaires (1996–2001) obtained intake data on a variety of foods. Beginning in 2005, women (18–30 years) reported whether they had ever been diagnosed with BBD that was confirmed by breast biopsy (n = 112 cases). Logistic regression estimated associations between intakes of vegetable protein and fat and biopsy-confirmed BBD. Those individual foods that were the largest contributors of protein and fat in this cohort were also investigated. In analyses of intakes from 1996 through 1998, when our cohort was youngest, vegetable fat (OR = 0.72/(10 gm/day), 95 % CI 0.53–0.98; p = 0.04) was inversely associated with BBD risk. The greatest sources of vegetable fat and protein in these girls were peanut butter, peanuts, nuts, beans (beans, lentils, and soybeans), and corn. A daily serving of any one of these was associated with lower risk (OR = 0.32/(serv/day), 95 % CI 0.13–0.79; p = 0.01). Peanut butter (and nuts) at age 11 years was inversely associated with risk (p = 0.01). In analyses of intakes at age 14 years, vegetable protein was associated with lower BBD risk (OR = 0.64/(10 gm/day), 95 % CI 0.43–0.95; p = 0.03). A daily serving at 14 years of any one of the foods was associated with lower risk (OR = 0.34, 95 % CI 0.16–0.75; p = 0.01), as was peanut butter (and nuts) (p = 0.02). Girls with a family history of breast cancer had significantly lower risk if they consumed these foods or vegetable fat. In conclusion, consumption of vegetable protein, fat, peanut butter, or nuts by older girls may help reduce their risk of BBD as young women.","title":"Vegetable protein and vegetable fat intakes in pre-adolescent and adolescent girls, and risk for benign breast disease in young women"},{"docid":"MED-719","text":"In addition to causing embarrassment and unease, flatulence is linked to a variety of symptoms, some of which may be distressing. This review describes the origins of intestinal gas, its composition and methods which have been developed for its analysis. Emphasis is placed upon the effects of legumes in the diet in producing excessive intestinal gas and, particularly, on the role of raffinose-type oligosaccharides, containing alpha-galactosidic groupings. Suggestions for overcoming the problem are presented, including drug treatment, enzyme treatment, food processing and plant breeding. It is emphasised that removal of all raffinose-oligosaccharides from beans does not remove the problem of flatulence in animals and man; the compounds responsible--though assumed to be polysaccharides (or polysaccharide-derived oligomers formed by processing or cooking)--have yet to be characterised.","title":"Flatulence--causes, relation to diet and remedies."},{"docid":"MED-724","text":"In addition to causing embarrassment and unease, flatulence is linked to a variety of symptoms, some of which may be distressing. This review describes the origins of intestinal gas, its composition and methods which have been developed for its analysis. Emphasis is placed upon the effects of legumes in the diet in producing excessive intestinal gas and, particularly, on the role of raffinose-type oligosaccharides, containing alpha-galactosidic groupings. Suggestions for overcoming the problem are presented, including drug treatment, enzyme treatment, food processing and plant breeding. It is emphasised that removal of all raffinose-oligosaccharides from beans does not remove the problem of flatulence in animals and man; the compounds responsible--though assumed to be polysaccharides (or polysaccharide-derived oligomers formed by processing or cooking)--have yet to be characterised.","title":"Flatulence--causes, relation to diet and remedies."},{"docid":"MED-890","text":"A case-control study was carried out in Harbin city to assess the role of diet in the aetiology of colorectal cancer. A total of 336 incident cases of histologically confirmed colorectal cancer (111 colon cancer and 225 rectal cancer) and an equal number of controls with other non-neoplastic diseases were interviewed in hospital wards. Data concerning the average frequency of consumption and amount consumed of single food items were obtained by a dietary history questionnaire. Odds ratios and their confidence limits were computed. Multiple regression for risk status was also used. Vegetables, particularly green vegetables, chives and celery, have a strong protective effect against colorectal cancer. Reduced consumption of meat, eggs, bean products and grain was associated with increasing risk for cancer of the rectum. Alcohol intake was found to be an important risk factor for developing colon cancer and male rectal cancer.","title":"Diet and cancer of the colon and rectum: a case-control study in China."},{"docid":"MED-4165","text":"Ergothioneine is a native membrane-impermeable thiol compound that is specifically accumulated in cells via the organic cation transporter OCTN1. In humans, OCTN1 and ergothioneine have been implicated in the etiopathogenesis of autoimmune disorders. However, available evidence about dietary sources and the functional role of ergothioneine in human physiology is scarce. Here, we analyzed the ergothioneine content in common foods using liquid chromatography tandem-mass spectrometry. Additionally, we assessed the protective potency of ergothioneine against various oxidative stressors in OCTN1-expressing cells in comparison with the main intracellular thiol antioxidant glutathione by evaluating cell viability with the MTT reduction assay. Only some food contained ergothioneine with highest concentrations detected in specialty mushrooms, kidney, liver, black and red beans, and oat bran. Ergothioneine exhibited cell protection only against copper(II)-induced toxicity but was far less potent than glutathione, indicting that ergothioneine is not involved in the intracellular antioxidant thiol defense system.","title":"Dietary sources and antioxidant effects of ergothioneine."},{"docid":"MED-875","text":"AIMS: The purpose of this study was to search for a novel quorum sensing inhibitor and analyse its inhibitory activity. METHODS AND RESULTS: Quorum sensing inhibition was monitored using the Tn-5 mutant, Chromobacterium violaceum CV026. Vanilla beans (Vanilla planifolia Andrews) were extracted using 75% (v/v) aqueous methanol and added to C. violaceum CV026 cultures. Inhibitory activity was measured by quantifying violacein production using a spectrophotometer. The results have revealed that vanilla extract significantly reduced violacein production in a concentration-dependent manner, indicating inhibition of quorum sensing. CONCLUSIONS: Vanilla, a widely used spice and flavour, can inhibit bacterial quorum sensing. SIGNIFICANCE AND IMPACT OF THE STUDY: The results suggest that the intake of vanilla-containing food materials might promote human health by inhibiting quorum sensing and preventing bacterial pathogenesis. Further studies are required to isolate specific substances from vanilla extract acting as quorum sensing inhibitors.","title":"Inhibition of bacterial quorum sensing by vanilla extract."},{"docid":"MED-5354","text":"This review focuses on the possible role in human health of the consumption of lignan-rich foods. Most of the plant lignans in human foods are converted by the intestinal microflora in the upper part of the large bowel to enterolactone and enterodiol, called mammalian or enterolignans. The protective role of these compounds, particularly in chronic Western diseases, is discussed. Evidence suggests that fiber- and lignan-rich whole-grain cereals, beans, berries, nuts, and various seeds are the main protective foods. Many factors, in addition to diet, such as intestinal microflora, smoking, antibiotics, and obesity affect circulating lignan levels in the body. Lignan-rich diets may be beneficial, particularly if consumed for life. Experimental evidence in animals has shown clear anticarcinogenic effects of flaxseed or pure lignans in many types of cancer. Many epidemiological results are controversial, partly because the determinants of plasma enterolactone are very different in different countries. The source of the lignans seems to play a role because other factors in the food obviously participate in the protective effects. The results are promising, but much work is still needed in this area of medicine.","title":"Lignans and human health."},{"docid":"MED-2195","text":"The objective of this study was to evaluate the precursors of acrylamide formation in sweet potato (SP) (Ipomoea batatas L. Lam) chips and to determine the effect of different types of vegetable oils (VOs), that is, palm olein, coconut oil, canola oil, and soya bean oil, on acrylamide formation. The reducing sugars and amino acids in the SP slices were analyzed, and the acrylamide concentrations of SP chips were measured. SP chips that were fried in a lower degree of unsaturation oils contained a lower acrylamide concentration (1443 μg/kg), whereas those fried with higher degree of unsaturated oils contained a higher acrylamide concentration (2019 μg/kg). SP roots were found to contain acrylamide precursors, that is, 4.17 mg/g glucose and 5.05 mg/g fructose, and 1.63 mg/g free asparagine. The type of VO and condition used for frying, significantly influenced acrylamide formation. This study clearly indicates that the contribution of lipids in the formation of acrylamide should not be neglected. © 2013 Institute of Food Technologists®","title":"The influence of deep frying using various vegetable oils on acrylamide formation in sweet potato (Ipomoea batatas L. Lam) chips."}],"string":"[\n {\n \"docid\": \"MED-3170\",\n \"text\": \"Background Few studies have focused on the cognitive morbidity of neurocysticercosis (NCC), one of the most common parasitic infections of the central nervous system. We longitudinally assessed the cognitive status and quality of life (QoL) of patients with incident symptomatic NCC cases and matched controls. Methodology/Principal Findings The setting of the study was the Sabogal Hospital and Cysticercosis Unit, Department of Transmissible Diseases, National Institute of Neurological Sciences, Lima, Peru. The design was a longitudinal study of new onset NCC cases and controls. Participants included a total of 14 patients with recently diagnosed NCC along with 14 healthy neighborhood controls and 7 recently diagnosed epilepsy controls. A standardized neuropsychological battery was performed at baseline and at 6 months on NCC cases and controls. A brain MRI was performed in patients with NCC at baseline and 6 months. Neuropsychological results were compared between NCC cases and controls at both time points. At baseline, patients with NCC had lower scores on attention tasks (p<0.04) compared with epilepsy controls but no significant differences compared to healthy controls. Six months after receiving anti-parasitic treatment, the NCC group significantly improved on tasks involving psychomotor speed (p<0.02). QoL at baseline suggested impaired mental function and social function in both the NCC and epilepsy group compared with healthy controls. QoL gains in social function (p = 0.006) were noted at 6 months in patients with NCC. Conclusions/Significance Newly diagnosed patients with NCC in this sample had mild cognitive deficits and more marked decreases in quality of life at baseline compared with controls. Improvements were found in both cognitive status and quality of life in patients with NCC after treatment. Author Summary Neurocysticercosis (NCC) is one of the most common parasitic infections of the central nervous system. Cognitive changes have been frequently reported with this disease but have not been well studied. Our study team recruited a group of new onset NCC cases and a matched set of healthy neighborhood controls and new onset epilepsy controls in Lima, Peru for this study. A neuropsychological battery was administered at baseline and at 6 months to all groups. Brain MRI studies were also obtained on NCC cases at baseline and at 6 months. Newly diagnosed patients with NCC had mild cognitive deficits and more marked decreases in quality of life at baseline compared with controls. Improvements were found in both cognitive status and quality of life in patients with NCC after treatment. This study is the first to assess cognitive status and quality of life longitudinally in patients with NCC and provides new data on an important clinical morbidity outcome.\",\n \"title\": \"Cognitive Changes and Quality of Life in Neurocysticercosis: A Longitudinal Study\"\n },\n {\n \"docid\": \"MED-3584\",\n \"text\": \"Background: A high intake of white rice is associated with the metabolic syndrome and type 2 diabetes. Costa Ricans follow a staple dietary pattern that includes white rice and beans, yet the combined role of these foods on cardiometabolic risk factors has not been studied. Objective: We aimed to determine the association between intake of white rice and beans and the metabolic syndrome and its components in Costa Rican adults (n = 1879) without diabetes. Design: Multivariate-adjusted means were calculated for components of the metabolic syndrome by daily servings of white rice and beans (<1, 1, or >1) and by the ratio of beans to white rice. The OR for the metabolic syndrome was calculated by substituting one serving of beans for one serving of white rice. Results: An increase in daily servings of white rice was positively associated with systolic blood pressure (BP), triglycerides, and fasting glucose and inversely associated with HDL cholesterol (P-trend <0.01 for all). An increase in servings of beans was inversely associated with diastolic BP (P = 0.049). Significant trends for higher HDL cholesterol and lower BP and triglycerides were observed for 1:3, 1:2, 1:1, and 2:1 ratios of beans to white rice. Substituting one serving of beans for one serving of white rice was associated with a 35% (95% CI: 15%, 50%) lower risk of the metabolic syndrome. Conclusion: Increasing the ratio of beans to white rice, or limiting the intake of white rice by substituting beans, may lower cardiometabolic risk factors.\",\n \"title\": \"A higher ratio of beans to white rice is associated with lower cardiometabolic risk factors in Costa Rican adults\"\n },\n {\n \"docid\": \"MED-2140\",\n \"text\": \"Background Around the world, beans and rice are commonly consumed together as a meal. With type 2 diabetes increasing, the effect of this traditional diet pattern on glycemic response has not been studied fully. Methods We evaluated the glycemic response of bean and rice traditional meals compared to rice alone in adults with type 2 diabetes. Seventeen men and women with type 2 diabetes controlled by metformin (n = 14) or diet/exercise (n = 3) aged 35–70 years participated in the randomized 4 × 4 crossover trial. The white long grain rice control, pinto beans/rice, black beans/rice, red kidney beans/rice test meals, matched for 50 grams of available carbohydrate, were consumed at breakfast after a 12 hour fast. Capillary blood glucose concentrations at baseline and at 30 minute intervals up to 180 minutes postprandial were collected. MANOVA for repeated measures established glucose differences between treatments. Paired t tests identified differences between bean types and the rice control following a significant MANOVA. Results Postprandial net glucose values were significantly lower for the three bean/rice treatments in contrast to the rice control at 90, 120 and 150 minutes. Incremental area under the curve values were significantly lower for the pinto and black bean/rice meals compared to rice alone, but not for kidney beans. Conclusions Pinto, dark red kidney and black beans with rice attenuate the glycemic response compared to rice alone. Promotion of traditional foods may provide non-pharmaceutical management of type 2 diabetes and improve dietary adherence with cultural groups. Trial registration Clinical Trials number NCT01241253\",\n \"title\": \"Bean and rice meals reduce postprandial glycemic response in adults with type 2 diabetes: a cross-over study\"\n },\n {\n \"docid\": \"MED-4991\",\n \"text\": \"BACKGROUND: Epidemiological studies have shown positive findings associated with legume consumption and measures of cardiovascular disease and obesity. However, few observational trials have examined beans as a separate food variable when determining associations with health parameters. OBJECTIVE: To determine the association of consuming beans on nutrient intakes and physiological parameters using the National Health and Examination Survey (NHANES) 1999-2002. METHODS: Using data from NHANES 1999-2002, a secondary analysis was completed with a reliable 24-hour dietary recall where three groups of bean consumers were identified (N = 1,475). We determined mean nutrient intakes and physiological values between bean consumers and non-consumers. Least square means, standard errors and ANOVA were calculated using appropriate sample weights following adjustment for age, gender, ethnicity and energy. RESULTS: Relative to non-consumers, bean consumers had higher intakes of dietary fiber, potassium, magnesium, iron, and copper (p's < 0.05). Those consuming beans had a lower body weight (p = 0.008) and a smaller waist size (p = 0.043) relative to non-consumers. Additionally, consumers of beans had a 23% reduced risk of increased waist size (p = 0.018) and a 22% reduced risk of being obese (p = 0.026). Also, baked bean consumption was associated with a lower systolic blood pressure. CONCLUSIONS: Bean consumers had better overall nutrient intake levels, better body weights and waist circumferences, and lower systolic blood pressure in comparison to non-consumers. These data support the benefits of bean consumption on improving nutrient intake and health parameters.\",\n \"title\": \"Bean consumption is associated with greater nutrient intake, reduced systolic blood pressure, lower body weight, and a smaller waist circumference ...\"\n },\n {\n \"docid\": \"MED-3138\",\n \"text\": \"Background Many consumers avoid eating beans because they believe legume consumption will cause excessive intestinal gas or flatulence. An increasing body of research and the 2010 Dietary Guidelines for Americans supports the benefits of a plant-based diet, and legumes specifically, in the reduction of chronic disease risks. The purpose of the current research was to investigate the perception of increased flatulence and gastrointestinal discomfort among participants who consumed a ½ cup of beans daily for 8 or 12 weeks. Methods Participants in three studies to test the effects of beans on heart disease biomarkers completed the same weekly questionnaire to assess gastrointestinal discomfort issues such as increased flatulence, stool changes, and bloating. Studies 1 and 2 were randomized crossover trials. Participants consumed ½ cup of pinto beans, black-eyed peas, and canned carrots as control (n = 17) in Study 1 for three randomized 8-week phases. For Study 2, participants ate ½ cup baked beans or canned carrots as control (n = 29) for two randomized 8-week phases. Study 3 was a parallel arm trial with 40 subjects receiving ½ cup pinto beans and 40 consuming a control soup for 12 weeks. Changes in the frequency of perceived flatulence, stool characteristics, and bloating were the primary outcome measures. Chi-square distributions were examined for the presence or absence of symptoms and demographic characteristics to determine differences by gender, age, body mass index (BMI), and bean type. Results Less than 50% reported increased flatulence from eating pinto or baked beans during the first week of each trial, but only 19% had a flatulence increase with black-eyed peas. A small percentage (3-11%) reported increased flatulence across the three studies even on control diets without flatulence-producing components. Conclusions People's concerns about excessive flatulence from eating beans may be exaggerated. Public health nutritionists should address the potential for gastrointestinal discomfort when increasing fiber intake from beans with clients. It is important to recognize there is individual variation in response to different bean types.\",\n \"title\": \"Perceptions of flatulence from bean consumption among adults in 3 feeding studies\"\n },\n {\n \"docid\": \"MED-1880\",\n \"text\": \"Legumes are the basés diet in several countries. They hold a high nutritional value, but other properties related to human health are nowadays being studied. The aim of this work was to study the influence of processes (boiling or germination) on the phenolic composition of dark beans (Phaseolus vulgaris L. c.v. Tolosana) and their effect on their antioxidant, neuroprotective and anticancer ability. Phenolic composition of raw and processed dark beans was analysed by HPLC-PAD and HPLC-ESI/MS. The antioxidant activity was evaluated by ORAC. Astrocytes cultures (U-373) have been used to test their neuroprotective effect. Anticancer activities were evaluated on three different cell lines (renal adenocarcinoma (TK-10), breast adenocarcinoma (MCF-7) and melanoma (UACC-62)) by sulphorhodamine B method. Qualitative and quantitative differences in phenolic composition have been observed between raw and processed dark beans that influence the antioxidant activity, mainly for germinated samples which show a decrease of antioxidant capacity. Although every assayed extracts decreased reactive oxygen species release and exhibited cytotoxicity activities on cancer cell lines, raw beans proved to be the most active in neuroprotective and antitumoral effects; this sample is especially rich in phenolic compounds, mainly anthocyanins. This study further demonstrated that phenolic composition of dark beans is related with cooking process and so with their neuroprotective and anticancer activity; cooking of dark beans improves their digestion and absorption at intestinal level, while maintaining its protective ability on oxidative process at cellular level. Copyright © 2012 Elsevier Ltd. All rights reserved.\",\n \"title\": \"Effect of cooking and germination on phenolic composition and biological properties of dark beans (Phaseolus vulgaris L.).\"\n },\n {\n \"docid\": \"MED-3141\",\n \"text\": \"OBJECTIVE: To evaluate the associations with chronic disease risk and mortality of the consequences of bean-free diets in Taiwanese adults with regard to gender. DESIGN: A sub-sample of the National Health Interview Survey (NHIS) in 2001 agreed to physical examination in the subsequent year. This group then took part in the Taiwanese Survey of Hyperglycaemia, Hyperlipidaemia and Hypertension (TwSHHH) in 2002. SETTING: Individual records were linked to the eventual death files from 2002 to 2008. SUBJECTS: Up to the end of 2008, a total of 2820 men and 2950 women were tracked by death registry over the 6·8 years of follow-up. RESULTS: Among 38,077 person-years, an average follow-up 6·5 years, 225 all-cause deaths were identified. Generalized linear models showed beans to be favourable for metabolic syndrome (other than for fasting glucose) in men; in women, beans were favourable for waist circumference and HbA1c. Cumulative logistic regression models for the effect of a bean-free diet on metabolic syndrome scores according to the Taiwanese-modified National Cholesterol Education Program-Adult Treatment Panel III (NCEP-tw) gave adjusted odds ratios of 1·83 in men and 1·45 in women. Cox regression models for the bean-free diet showed an increased hazard ratio for all-cause mortality among women (1·98, 95% CI 1·03, 3·81) but not men (1·28, 95% CI 0·76, 2·16). CONCLUSIONS: A bean-free diet may play a role in developing the metabolic syndrome in both genders, and is a significant predictor of all-cause mortality in Taiwanese women but not men.\",\n \"title\": \"A bean-free diet increases the risk of all-cause mortality among Taiwanese women: the role of the metabolic syndrome.\"\n },\n {\n \"docid\": \"MED-5079\",\n \"text\": \"OBJECTIVE: To determine effects of daily intake of 1/2 cup pinto beans, black-eyed peas or carrots (placebo) on risk factors for coronary heart disease (CHD) and diabetes mellitus (DM) in free-living, mildly insulin resistant adults over an 8 week period. METHODS: Randomized, crossover 3x3 block design. Sixteen participants (7 men, 9 women) received each treatment for eight-weeks with two-week washouts. Fasting blood samples collected at beginning and end of periods were analyzed for total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol, triacylglycerols, high-sensitivity C-reactive protein, insulin, glucose, and hemoglobin A1c. RESULTS: A significant treatment-by-time effect impacted serum TC (p = 0.026) and LDL (p = 0.033) after eight weeks. Paired t-tests indicated that pinto beans were responsible for this effect (p = 0.003; p = 0.008). Mean change of serum TC for pinto bean, black-eyed pea and placebo were -19 +/- 5, 2.5 +/- 6, and 1 +/- 5 mg/dL, respectively (p = 0.011). Mean change of serum LDL-C for pinto bean, black-eyed pea and placebo were -14 +/- 4, 4 +/- 5, and 1 +/- 4 mg/dL, in that order (p = 0.013). Pinto beans differed significantly from placebo (p = 0.021). No significant differences were seen with other blood concentrations across the 3 treatment periods. CONCLUSIONS: Pinto bean intake should be encouraged to lower serum TC and LDL-C, thereby reducing risk for CHD.\",\n \"title\": \"Pinto bean consumption reduces biomarkers for heart disease risk.\"\n },\n {\n \"docid\": \"MED-2570\",\n \"text\": \"The functional properties, including antioxidant and chemopreventative capacities as well as the inhibitory effects on angiotensin-converting enzyme (ACE), α-glucosidase and pancreatic lipase, of three Australian-grown faba bean genotypes (Nura, Rossa and TF(Ic*As)*483/13) were investigated using an array of in vitro assays. Chromatograms of on-line post column derivatisation assay coupled with HPLC revealed the existence of active phenolics (hump) in the coloured genotypes, which was lacking in the white-coloured breeding line, TF(Ic*As)*483/13. Roasting reduced the phenolic content, and diminished antioxidant activity by 10-40 % as measured by the reagent-based assays (diphenylpicrylhydrazyl, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) and oxygen radical absorbance capacity) in all genotypes. Cell culture-based antioxidant activity assay (cellular antioxidant activity) showed an increase of activity in the coloured genotypes after roasting. Faba bean extracts demonstrated cellular protection ability against H₂O₂-induced DNA damage (assessed using RAW264.7 cells), and inhibited the proliferation of all human cancer cell lines (BL13, AGS, Hep G2 and HT-29) evaluated. However, the effect of faba bean extracts on the non-transformed human cells (CCD-18Co) was negligible. Flow cytometric analyses showed that faba bean extracts successfully induced apoptosis of HL-60 (acute promyelocytic leukaemia) cells. The faba bean extracts also exhibited ACE, α-glucosidase and pancreatic lipase inhibitory activities. Overall, extracts from Nura (buff-coloured) and Rossa (red-coloured) were comparable, while TF(Ic*As)*483/13 (white-coloured) contained the lowest phenolic content and exhibited the least antioxidant and enzyme inhibition activities. These results are important to promote the utilisation of faba beans in human diets for various health benefits.\",\n \"title\": \"In vitro investigations of the potential health benefits of Australian-grown faba beans (Vicia faba L.): chemopreventative capacity and inhibitory ...\"\n },\n {\n \"docid\": \"MED-3136\",\n \"text\": \"The objective of this study was to determine the influence of frequent and long-term consumption of legume seeds on colonic function. Two groups of subjects were studied--one group habitually consumed legume seeds as part of their normal diet, a second group only infrequently consumed legumes. No differences between these groups could be detected for fecal output and frequency, intestinal transit time, VFA excretion or fecal pH during 23-day study periods in which subjects consumed either their usual diet or 100 g red kidney beans, daily. However, the addition of beans to the diets of both groups provided significantly more dietary fiber, and produced greater fecal output and a higher concentration of VFA in feces. Fecal output appeared to be determined by two independent parameters--dietary fiber intake and VFA excretion. Beans provided a physiologically useful source of dietary fiber and favorably influenced colonic function.\",\n \"title\": \"Influence of frequent and long-term bean consumption on colonic function and fermentation.\"\n },\n {\n \"docid\": \"MED-2147\",\n \"text\": \"Consumption of Phaseolus vulgaris bean species such as pinto, black, navy or kidney may be beneficial in the prevention and treatment of chronic diseases. In particular, conditions that are promoted by increased glycaemic stress (hyperglycaemia and hyperinsulinaemia) including diabetes, CVD and cancer seem to be reduced in individuals who eat more of these beans. The present paper discusses the influence of P. vulgaris species on glycaemic response and the impact that relationship may have on the risk of developing diabetes, CVD and cancer.\",\n \"title\": \"Phaseolus beans: impact on glycaemic response and chronic disease risk in human subjects.\"\n },\n {\n \"docid\": \"MED-2580\",\n \"text\": \"Adequate fruit and vegetable intake was suggested to protect against colorectal cancer and colorectal adenomas; however, several recent prospective studies reported no association. We examined the association between fruits and vegetables and adenomatous polyp recurrence in the Polyp Prevention Trial (PPT). The PPT was a low-fat, high-fiber, high-fruit, and vegetable dietary intervention trial of adenoma recurrence, in which there were no differences in the rate of adenoma recurrence in participants in the intervention and control arms of the trial. In this analysis of the entire PPT trial–based cohort, multiple logistic regression analysis was used to estimate the odds ratio (OR) of advanced and nonadvanced adenoma recurrence within quartiles of baseline and change (baseline minus the mean over 3 y) in fruit and vegetable intake, after adjustment for age, total energyy intake, use of nonsteroidal anti-inflammatory drugs, BMI, and gender. There were no significant associations between nonadvanced adenoma recurrence and overall change in fruit and vegetable consumption; however, those in the highest quartile of change in dry bean intake (greatest increase) compared with those in the lowest had a significantly reduced OR for advanced adenoma recurrence (OR = 0.35; 95% CI, 0.18–0.69; P for trend = 0.001). The median in the highest quartile of change in dry bean intake was 370% higher than the baseline intake. The PPT trial–based cohort provides evidence that dry beans may be inversely associated with advanced adenoma recurrence.\",\n \"title\": \"High Dry Bean Intake and Reduced Risk of Advanced Colorectal Adenoma Recurrence among Participants in the Polyp Prevention Trial\"\n },\n {\n \"docid\": \"MED-2144\",\n \"text\": \"Bean pods (Phaseolus vulgaris) are among the most widely used traditional remedies against diabetes mellitus. Historical knowledge is summarized and compared to recent study results. Reports dating from the first half of the 20(th) century as well as recent publications show contradictory results. It seems that Phaseolus preparations should not be considered the first choice in phytopharmaceutical treatment of diabetes or lead structure research. To be effective, fairly high doses of aqueous extracts need to be given. Because of their fiber content and an alpha-amylase inhibitory effect, beans might be more useful as food components in preventing or ameliorating type 2 diabetes.\",\n \"title\": \"Beans and diabetes: Phaseolus vulgaris preparations as antihyperglycemic agents.\"\n },\n {\n \"docid\": \"MED-2010\",\n \"text\": \"Legumes (including alfalfa, clover, lupins, green beans and peas, peanuts, soybeans, dry beans, broad beans, dry peas, chickpeas, and lentils) represent an important component of the human diet in several areas of the world, especially in the developing countries, where they complement the lack of proteins from cereals, roots, and tubers. In some regions of the world, legume seeds are the only protein supply in the diet. The health benefits of legume consumption have received rising interest from researchers, and their consumption and production extends worldwide. Among European countries, higher legume consumption is observed around the Mediterranean, with per capita daily consumption between 8 and 23 g, while in Northern Europe, the daily consumption is less than 5 g per capita. The physiological effects of different legumes vary significantly. These differences may result from the polysaccharides composition, in particular, the quantity and variety of dietary fibers and starch, protein make-up, and variability in phytochemical content. The majority of legumes contain phytochemicals: bioactive compounds, including enzyme inhibitors, phytohemagglutinins (lectins), phytoestrogens, oligosaccharides, saponins, and phenolic compounds, which play metabolic roles in humans who frequently consume these foods. Dietary intake of phytochemicals may provide health benefits, protecting against numerous diseases or disorders, such as coronary heart disease, diabetes, high blood pressure and inflammation. The synergistic or antagonistic effects of these phytochemical mixtures from food legumes, their interaction with other components of the diet, and the mechanism of their action have remained a challenge with regard to understanding the role of phytochemicals in health and diseases. Their mitigating effects and the mechanism of their action need to be further addressed if we are to understand the role of phytochemicals in health and diseases. This review provides an overview of the nutritional quality of legumes and their potential contribution in cardiometabolic risk prevention.\",\n \"title\": \"Nutritional quality of legumes, and their role in cardiometabolic risk prevention: a review.\"\n },\n {\n \"docid\": \"MED-5078\",\n \"text\": \"In this study, solid fermentation of steamed black soybean with various GRAS (Generally recognized as safe) filamentious-fungi including Aspergillus awamori, Aspergillus oryzae BCRC 30222, Aspergillus sojae BCRC 30103, Rhizopus azygosporus BCRC 31158 and Rhizopus sp. No. 2 was performed. Mutagenicity and antimutagenicity of the methanol extracts of unfermented and fermented steamed black soybeans against 4-nitroquinoline-N-oxide (4-NQO), a direct mutagen and Benzo[a]pyrene (B[a]P), an indirect mutagen, on Salmonella Typhimurium TA100 and TA 98, were examined. The methanol extracts of unfermented and fermented steamed black soybeans show no mutagenic activity for either test strains at the doses tested. The extracts inhibited mutagenesis by either 4-NQO or B[a]P in S. Typhimurium TA100 and TA98. Fermentation with fungi also enhanced the antimutagenic effect of black soybean while the antimutagenic effect of the fermented black soybeans extract varied with the starter organism, mutagen, and test strain of S. Typhimurium examined. Generally, the extracts of A. awamori-fermented black soybean exhibited the highest antimutagenic effect. With strain TA100, the inhibitory effects of 5.0 mg of A. awamori-fermented black soybean extract per plate on the mutagenic effects of 4-NQO and B[a]P were 92% and 89%, respectively, while the corresponding rates for extract of unfermented were 41% and 63%, respectively. With strain 98, the inhibition rates were 94 and 81% for the fermented bean extract and 58% and 44% for the unfermented bean extracts. Testing of extracts prepared from black soybean by A. awamori at temperatures 25, 30 and 35 degrees C and for times of 1-5 days revealed that, generally, the extract prepared from beans fermented at 30 degrees C for 3 days exhibited the greatest inhibition against the mutagenic effects of 4-NQO and B[a]P.\",\n \"title\": \"Mutagenic and antimutagenic effects of methanol extracts of unfermented and fermented black soybeans.\"\n },\n {\n \"docid\": \"MED-2141\",\n \"text\": \"We investigated the association between dietary patterns and insulin resistance in the 3871 healthy Korean adults from the 2007 to 2008 Korea National Health and Nutrition Examination Survey. The whole grains and beans pattern was associated with lower prevalence of insulin resistance (OR for highest quintile=0.80, 95% CI=0.61-1.03, P for trend=0.013). Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.\",\n \"title\": \"High intake of whole grains and beans pattern is inversely associated with insulin resistance in healthy Korean adult population.\"\n },\n {\n \"docid\": \"MED-5080\",\n \"text\": \"Bioactivity-guided fractionation of black bean (Phaseolus vulgaris) seed coats was used to determine the chemical identity of bioactive constituents, which showed potent antiproliferative and antioxidative activities. Twenty-four compounds including 12 triterpenoids, 7 flavonoids, and 5 other phytochemicals were isolated using gradient solvent fractionation, silica gel and ODS columns, and semipreparative and preparative HPLC. Their chemical structures were identified using MS, NMR, and X-ray diffraction analysis. Antiproliferative activities of isolated compounds against Caco-2 human colon cancer cells, HepG2 human liver cancer cells, and MCF-7 human breast cancer cells were evaluated. Among the compounds isolated, compounds 1, 2, 6, 7, 8, 13, 14, 15, 16, 19, and 20 showed potent inhibitory activities against the proliferation of HepG2 cells, with EC50 values of 238.8 +/- 19.2, 120.6 +/- 7.3, 94.4 +/- 3.4, 98.9 +/- 3.3, 32.1 +/- 6.3, 306.4 +/- 131.3, 156.9 +/- 11.8, 410.3 +/- 17.4, 435.9 +/- 47.7, 202.3 +/- 42.9, and 779.3 +/- 37.4 microM, respectively. Compounds 1, 2, 3, 5, 6, 7, 8, 9, 10, 11, 14, 15, 19, and 20 showed potent antiproliferative activities against Caco-2 cell growth, with EC50 values of 179.9 +/- 16.9, 128.8 +/- 11.6, 197.8 +/- 4.2, 105.9 +/- 4.7, 13.9 +/- 2.8, 35.1 +/- 2.9, 31.2 +/- 0.5, 71.1 +/- 11.9, 40.8 +/- 4.1, 55.7 +/- 8.1, 299.8 +/- 17.3, 533.3 +/- 126.0, 291.2 +/- 1.0, and 717.2 +/- 104.8 microM, respectively. Compounds 5, 7, 8, 9, 11, 19, 20 showed potent antiproliferative activities against MCF-7 cell growth in a dose-dependent manner, with EC50 values of 129.4 +/- 9.0, 79.5 +/- 1.0, 140.1 +/- 31.8, 119.0 +/- 7.2, 84.6 +/- 1.7, 186.6 +/- 21.1, and 1308 +/- 69.9 microM, respectively. Six flavonoids (compounds 14-19) showed potent antioxidant activity. These results showed the phytochemical extracts of black bean seed coats have potent antioxidant and antiproliferative activities.\",\n \"title\": \"Phytochemicals of black bean seed coats: isolation, structure elucidation, and their antiproliferative and antioxidative activities.\"\n },\n {\n \"docid\": \"MED-3132\",\n \"text\": \"Little is known about dietitians current practice in counselling clients about the use of legumes in a low fat, high fibre diet. An exploratory e-mail questionnaire was sent to members of Dietitians of Canada to assess: dietitian use and preferences for legumes, dietitian practice, opinions about clients attitudes and preferences, and resource needs. Counsellors (n=256) had high personal use of legumes (64% > or = 1 serving/week) and frequently recommended legumes in counselling. The legumes most preferred by respondents and their clients were: peanuts, kidney beans, split peas, chickpeas, and lentils. Respondents often recommended canned bean products (76%) and tofu (61%), but other legume grocery products were less often recommended. The most common client issues identified were: flatulence (87% agreed), lack of familiarity (85%), and knowledge of preparation (82%). Dietitians were not satisfied with current resources to support practice, especially those respondents providing primarily clinical counselling services. The most requested resources were: recipes (90%), pamphlets (82%), food demonstrations (75%) and Internet sites (63%). Client level research is now needed to confirm the importance of the issues identified and to develop and test strategies for legume promotion in counselling.\",\n \"title\": \"Legume promotion in counselling: an e-mail survey of dietitians.\"\n },\n {\n \"docid\": \"MED-2085\",\n \"text\": \"A diet rich in fruits and vegetables is known to decrease the risk of cardiovascular disease. However, the information regarding the antithrombotic activity (antiplatelet, anticoagulant, and fibrinolytic) of fruits and vegetables is scarce. The aim of this study was to assess the antithrombotic activity of extracts from fruits and vegetables widely consumed in central Chile. The study included samples of 19 fruits and 26 vegetables, representative of the local diet. The extracts prepared from each sample included an aqueous (juice or pressed solubles) and/or methanol-soluble fraction. The extracts were evaluated for antiplatelet, anticoagulant, and fibrinolytic activity in vitro at a final concentration of 1 mg/ml. The antiplatelet activity was assessed by platelet aggregation inhibition; anticoagulant activity was measured by the prothrombin time (PT), diluted prothrombin time (dPT), activated partial thromboplastin time (APTT), kaolin clotting time (KCT), and thrombin time. The fibrinolytic effect was determined with the euglobin clot lysis time and fibrin plate methods. Extracts of green beans and tomatoes inhibited platelet aggregation induced by ADP and arachidonic acid, in a concentration-dependent manner. The methanolic extracts of grapes prolonged the PT and dPT. Finally, extracts of raspberry prolonged the APTT and also presented fibrinolytic activity. In conclusion, from a screening that included a variety of fruits and vegetables, we found antiplatelet activity in green beans and tomatoes, anticoagulant activities in grapes and raspberries, whereas fibrinolytic activity was observed only in raspberries. Further investigations are necessary to advance in knowledge of the active compounds of these fruits and vegetables and their mechanisms of action.\",\n \"title\": \"Antiplatelet, anticoagulant, and fibrinolytic activity in vitro of extracts from selected fruits and vegetables.\"\n },\n {\n \"docid\": \"MED-5118\",\n \"text\": \"OBJECTIVE: To compare the effects of two commercially available soy milks (one made using whole soy beans, the other using soy protein isolate) with low-fat dairy milk on plasma lipid, insulin, and glucose responses. DESIGN: Randomized clinical trial, cross-over design. SUBJECTS: Participants were 30-65 years of age, n = 28, with pre-study LDL-cholesterol (LDL-C) concentrations of 160-220 mg/dL, not on lipid lowering medications, and with an overall Framingham risk score of or=4 weeks. RESULTS: Mean LDL-C concentration at the end of each phase (+/- SD) was 161 +/- 20, 161 +/- 26 and 170 +/- 24 mg/dL for the whole bean soy milk, the soy protein isolate milk, and the dairy milk, respectively (p = 0.9 between soy milks, p = 0.02 for each soy milk vs. dairy milk). No significant differences by type of milk were observed for HDL-cholesterol, triacylglycerols, insulin, or glucose. CONCLUSION: A 25 g dose of daily soy protein from soy milk led to a modest 5% lowering of LDL-C relative to dairy milk among adults with elevated LDL-C. The effect did not differ by type of soy milk and neither soy milk significantly affected other lipid variables, insulin or glucose.\",\n \"title\": \"Effect of two types of soy milk and dairy milk on plasma lipids in hypercholesterolemic adults: a randomized trial.\"\n },\n {\n \"docid\": \"MED-3894\",\n \"text\": \"The purpose of this study was to examine the effects of a natural carbohydrate (CHO) source in the form of sun-dried raisins (SDRs) vs. Sports Jelly Beans™ (SJBs) on endurance performance in trained cyclists and triathletes. Ten healthy men (18-33 years) completed 1 water-only acclimatization exercise trial and 2 randomized exercise trials administered in a crossover fashion. Each trial consisted of a 120-minute constant-intensity glycogen depletion period followed by a 10-km time trial (TT). During each experimental trial, participants consumed isocaloric amounts of SDRs or SJBs in 20-minute intervals. Measurements included time to complete 10-km TT, power output during 10-km TT, blood glucose levels and respiratory exchange ratio during glycogen depletion period, rate of perceived exertion (RPE), 'flow' questionnaire responses, and a hedonic (i.e., pleasantness) sensory acceptance test. There were no significant differences in endurance performance for TT time (SDRs vs. SJBs, 17.3 ± 0.4 vs. 17.3 ± 0.4 seconds) or power (229.3 ± 13.0 vs. 232.0 ± 13.6 W), resting blood glucose levels (5.8 ± 04 mmol·L(-1) for SDRs and 5.4 ± 0.2 mmol·L(-1) for SJBs), RPE, or flow experiences between SDR and SJB trials. However, the mean sensory acceptance scores were significantly higher for the SDRs compared to the SJBs (50.7 ± 1.7 vs. 44.3 ± 2.7). Consuming SDRs or SJBs during 120 minutes of intense cycling results in similar subsequent TT performances and are equally effective in maintaining blood glucose levels during exercise. Therefore, SDRs are a natural, pleasant, cost-effective CHO alternative to commercial SJBs that can be used during moderate- to high-intensity endurance exercise.\",\n \"title\": \"Sun-dried raisins are a cost-effective alternative to Sports Jelly Beans in prolonged cycling.\"\n },\n {\n \"docid\": \"MED-4869\",\n \"text\": \"This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of various food additives, including flavouring agents, with a view to recommending acceptable daily intakes (ADIs) and to preparing specifications for identity and purity. The first part of the report contains a general discussion of the principles governing the toxicological evaluation and assessment of intake of food additives (in particular, flavouring agents). A summary follows of the Committee's evaluations of technical, toxicological and intake data for certain food additives (asparaginase from Aspergillus niger expressed in A. niger, calcium lignosulfonate (40-65), ethyl lauroyl arginate, paprika extract, phospholipase C expressed in Pichia pastoris, phytosterols, phytostanols and their esters, polydimethylsiloxane, steviol glycosides and sulfites [assessment of dietary exposure]) and 10 groups of related flavouring agents (aliphatic branched-chain saturated and unsaturated alcohols, aldehydes, acids and related esters; aliphatic linear alpha,beta-unsaturated aldehydes, acids and related alcohols, acetals and esters; aliphatic secondary alcohols, ketones and related esters; alkoxy-substituted allylbenzenes present in foods and essential oils and used as flavouring agents; esters of aliphatic acyclic primary alcohols with aliphatic linear saturated carboxylic acids; furan-substituted aliphatic hydrocarbons, alcohols, aldehydes, ketones, carboxylic acids and related esters, sulfides, disulfides and ethers; miscellaneous nitrogen-containing substances; monocyclic and bicyclic secondary alcohols, ketones and related esters; hydroxy- and alkoxy-substituted benzyl derivatives; and substances structurally related to menthol). Specifications for the following food additives were revised: canthaxanthin; carob bean gum and carob bean gum (clarified); chlorophyllin copper complexes, sodium and potassium salts; Fast Green FCF; guar gum and guar gum (clarified); iron oxides; isomalt; monomagnesium phosphate; Patent Blue V; Sunset Yellow FCF; and trisodium diphosphate. Re-evaluation of flavouring agents for which estimated intake was based on anticipated poundage data was carried out for 2-isopropyl- N,2,3-trimethylbutyramide (No. 1595) and L-monomenthyl glutarate (No. 1414). Annexed to the report are tables summarizing the Committee's recommendations for intakes and toxicological evaluations of the food additives considered.\",\n \"title\": \"Evaluation of certain food additives.\"\n },\n {\n \"docid\": \"MED-2150\",\n \"text\": \"Previous investigations, of adolescent diet recalled in adulthood, found lower risk for benign breast disease (BBD) with higher intakes of vegetable fat and nuts during high school. We investigate whether vegetable protein and fat, derived from diets reported during pre-adolescence and adolescence, are associated with subsequent risk for BBD in young women. The Growing Up Today Study includes 9,039 females, 9–15 years in 1996, who completed questionnaires annually through 2001, and then in 2003, 2005, 2007, and 2010. Food frequency questionnaires (1996–2001) obtained intake data on a variety of foods. Beginning in 2005, women (18–30 years) reported whether they had ever been diagnosed with BBD that was confirmed by breast biopsy (n = 112 cases). Logistic regression estimated associations between intakes of vegetable protein and fat and biopsy-confirmed BBD. Those individual foods that were the largest contributors of protein and fat in this cohort were also investigated. In analyses of intakes from 1996 through 1998, when our cohort was youngest, vegetable fat (OR = 0.72/(10 gm/day), 95 % CI 0.53–0.98; p = 0.04) was inversely associated with BBD risk. The greatest sources of vegetable fat and protein in these girls were peanut butter, peanuts, nuts, beans (beans, lentils, and soybeans), and corn. A daily serving of any one of these was associated with lower risk (OR = 0.32/(serv/day), 95 % CI 0.13–0.79; p = 0.01). Peanut butter (and nuts) at age 11 years was inversely associated with risk (p = 0.01). In analyses of intakes at age 14 years, vegetable protein was associated with lower BBD risk (OR = 0.64/(10 gm/day), 95 % CI 0.43–0.95; p = 0.03). A daily serving at 14 years of any one of the foods was associated with lower risk (OR = 0.34, 95 % CI 0.16–0.75; p = 0.01), as was peanut butter (and nuts) (p = 0.02). Girls with a family history of breast cancer had significantly lower risk if they consumed these foods or vegetable fat. In conclusion, consumption of vegetable protein, fat, peanut butter, or nuts by older girls may help reduce their risk of BBD as young women.\",\n \"title\": \"Vegetable protein and vegetable fat intakes in pre-adolescent and adolescent girls, and risk for benign breast disease in young women\"\n },\n {\n \"docid\": \"MED-719\",\n \"text\": \"In addition to causing embarrassment and unease, flatulence is linked to a variety of symptoms, some of which may be distressing. This review describes the origins of intestinal gas, its composition and methods which have been developed for its analysis. Emphasis is placed upon the effects of legumes in the diet in producing excessive intestinal gas and, particularly, on the role of raffinose-type oligosaccharides, containing alpha-galactosidic groupings. Suggestions for overcoming the problem are presented, including drug treatment, enzyme treatment, food processing and plant breeding. It is emphasised that removal of all raffinose-oligosaccharides from beans does not remove the problem of flatulence in animals and man; the compounds responsible--though assumed to be polysaccharides (or polysaccharide-derived oligomers formed by processing or cooking)--have yet to be characterised.\",\n \"title\": \"Flatulence--causes, relation to diet and remedies.\"\n },\n {\n \"docid\": \"MED-724\",\n \"text\": \"In addition to causing embarrassment and unease, flatulence is linked to a variety of symptoms, some of which may be distressing. This review describes the origins of intestinal gas, its composition and methods which have been developed for its analysis. Emphasis is placed upon the effects of legumes in the diet in producing excessive intestinal gas and, particularly, on the role of raffinose-type oligosaccharides, containing alpha-galactosidic groupings. Suggestions for overcoming the problem are presented, including drug treatment, enzyme treatment, food processing and plant breeding. It is emphasised that removal of all raffinose-oligosaccharides from beans does not remove the problem of flatulence in animals and man; the compounds responsible--though assumed to be polysaccharides (or polysaccharide-derived oligomers formed by processing or cooking)--have yet to be characterised.\",\n \"title\": \"Flatulence--causes, relation to diet and remedies.\"\n },\n {\n \"docid\": \"MED-890\",\n \"text\": \"A case-control study was carried out in Harbin city to assess the role of diet in the aetiology of colorectal cancer. A total of 336 incident cases of histologically confirmed colorectal cancer (111 colon cancer and 225 rectal cancer) and an equal number of controls with other non-neoplastic diseases were interviewed in hospital wards. Data concerning the average frequency of consumption and amount consumed of single food items were obtained by a dietary history questionnaire. Odds ratios and their confidence limits were computed. Multiple regression for risk status was also used. Vegetables, particularly green vegetables, chives and celery, have a strong protective effect against colorectal cancer. Reduced consumption of meat, eggs, bean products and grain was associated with increasing risk for cancer of the rectum. Alcohol intake was found to be an important risk factor for developing colon cancer and male rectal cancer.\",\n \"title\": \"Diet and cancer of the colon and rectum: a case-control study in China.\"\n },\n {\n \"docid\": \"MED-4165\",\n \"text\": \"Ergothioneine is a native membrane-impermeable thiol compound that is specifically accumulated in cells via the organic cation transporter OCTN1. In humans, OCTN1 and ergothioneine have been implicated in the etiopathogenesis of autoimmune disorders. However, available evidence about dietary sources and the functional role of ergothioneine in human physiology is scarce. Here, we analyzed the ergothioneine content in common foods using liquid chromatography tandem-mass spectrometry. Additionally, we assessed the protective potency of ergothioneine against various oxidative stressors in OCTN1-expressing cells in comparison with the main intracellular thiol antioxidant glutathione by evaluating cell viability with the MTT reduction assay. Only some food contained ergothioneine with highest concentrations detected in specialty mushrooms, kidney, liver, black and red beans, and oat bran. Ergothioneine exhibited cell protection only against copper(II)-induced toxicity but was far less potent than glutathione, indicting that ergothioneine is not involved in the intracellular antioxidant thiol defense system.\",\n \"title\": \"Dietary sources and antioxidant effects of ergothioneine.\"\n },\n {\n \"docid\": \"MED-875\",\n \"text\": \"AIMS: The purpose of this study was to search for a novel quorum sensing inhibitor and analyse its inhibitory activity. METHODS AND RESULTS: Quorum sensing inhibition was monitored using the Tn-5 mutant, Chromobacterium violaceum CV026. Vanilla beans (Vanilla planifolia Andrews) were extracted using 75% (v/v) aqueous methanol and added to C. violaceum CV026 cultures. Inhibitory activity was measured by quantifying violacein production using a spectrophotometer. The results have revealed that vanilla extract significantly reduced violacein production in a concentration-dependent manner, indicating inhibition of quorum sensing. CONCLUSIONS: Vanilla, a widely used spice and flavour, can inhibit bacterial quorum sensing. SIGNIFICANCE AND IMPACT OF THE STUDY: The results suggest that the intake of vanilla-containing food materials might promote human health by inhibiting quorum sensing and preventing bacterial pathogenesis. Further studies are required to isolate specific substances from vanilla extract acting as quorum sensing inhibitors.\",\n \"title\": \"Inhibition of bacterial quorum sensing by vanilla extract.\"\n },\n {\n \"docid\": \"MED-5354\",\n \"text\": \"This review focuses on the possible role in human health of the consumption of lignan-rich foods. Most of the plant lignans in human foods are converted by the intestinal microflora in the upper part of the large bowel to enterolactone and enterodiol, called mammalian or enterolignans. The protective role of these compounds, particularly in chronic Western diseases, is discussed. Evidence suggests that fiber- and lignan-rich whole-grain cereals, beans, berries, nuts, and various seeds are the main protective foods. Many factors, in addition to diet, such as intestinal microflora, smoking, antibiotics, and obesity affect circulating lignan levels in the body. Lignan-rich diets may be beneficial, particularly if consumed for life. Experimental evidence in animals has shown clear anticarcinogenic effects of flaxseed or pure lignans in many types of cancer. Many epidemiological results are controversial, partly because the determinants of plasma enterolactone are very different in different countries. The source of the lignans seems to play a role because other factors in the food obviously participate in the protective effects. The results are promising, but much work is still needed in this area of medicine.\",\n \"title\": \"Lignans and human health.\"\n },\n {\n \"docid\": \"MED-2195\",\n \"text\": \"The objective of this study was to evaluate the precursors of acrylamide formation in sweet potato (SP) (Ipomoea batatas L. Lam) chips and to determine the effect of different types of vegetable oils (VOs), that is, palm olein, coconut oil, canola oil, and soya bean oil, on acrylamide formation. The reducing sugars and amino acids in the SP slices were analyzed, and the acrylamide concentrations of SP chips were measured. SP chips that were fried in a lower degree of unsaturation oils contained a lower acrylamide concentration (1443 μg/kg), whereas those fried with higher degree of unsaturated oils contained a higher acrylamide concentration (2019 μg/kg). SP roots were found to contain acrylamide precursors, that is, 4.17 mg/g glucose and 5.05 mg/g fructose, and 1.63 mg/g free asparagine. The type of VO and condition used for frying, significantly influenced acrylamide formation. This study clearly indicates that the contribution of lipids in the formation of acrylamide should not be neglected. © 2013 Institute of Food Technologists®\",\n \"title\": \"The influence of deep frying using various vegetable oils on acrylamide formation in sweet potato (Ipomoea batatas L. Lam) chips.\"\n }\n]"}}},{"rowIdx":196,"cells":{"query_id":{"kind":"string","value":"8738"},"query":{"kind":"string","value":"When to convert employee shares in an RRSP into cash, even if there is a penalty?"},"positive_passages":{"kind":"list like","value":[{"docid":"432511","text":"The cost to you for selling is 3/8% of a years salary, this is what you won't get if you sell. Tough to calculate the what-if scenarios beyond this, since I can't quantify the risk of a price drop. Once the amount in he stock is say,10%, of a years salary, if you know a drop is coming, a sale is probably worth it, for a steep drop. My stronger focus would be on how much of your wealth is concentrated in that one stock, Enron, and all.","title":""}],"string":"[\n {\n \"docid\": \"432511\",\n \"text\": \"The cost to you for selling is 3/8% of a years salary, this is what you won't get if you sell. Tough to calculate the what-if scenarios beyond this, since I can't quantify the risk of a price drop. Once the amount in he stock is say,10%, of a years salary, if you know a drop is coming, a sale is probably worth it, for a steep drop. My stronger focus would be on how much of your wealth is concentrated in that one stock, Enron, and all.\",\n \"title\": \"\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"432902","text":"\"Your question is based on incorrect assumptions. Generally, there's no \"\"penalty\"\", per se, to make a withdrawal from your RRSP, even if you make a withdrawal earlier than retirement, however you define it. A precise meaning for \"\"retirement\"\" with respect to RRSPs is largely irrelevant.* Our U.S. neighbours have a 10% penalty on non-hardship early withdrawals (before age 59 ½) from retirement accounts like the 401k and IRA. It's an additional measure designed to discourage early withdrawals, and raise more tax. Yet, in Canada, there is no similar penalty. Individual investments inside your RRSP may have associated penalties, such as the dreaded \"\"deferred sales charge\"\" (DSC) of some back-end loaded mutual funds, or such as LSVCC funds that generated additional special tax credits that could get clawed back. Yet, these early withdrawal penalties are distinct from the RRSP nature of your account. Choose your investments carefully to avoid these kinds of surprises. Rather, an RRSP is a tax-deferred account, and it works like this: The government allows you to claim a nice juicy tax deduction, which can reduce your income tax at your marginal rate in the year you make a contribution, or later if you should choose to defer the deduction. The resulting pre-tax money accumulated in your RRSP benefits from further tax deferral: assets can grow without attracting annual income tax on earned interest, dividends, or capital gains. You don't need to declare on your income tax return any of the income earned inside your RRSP, unlike a regular investment account. Here's the rub: Once you decide to withdraw money from your RRSP, the entire amount withdrawn is considered regular income in the year in which you make the withdrawal. Thus, your withdrawals are subject to income tax, and yes, at your marginal rate. This is always the case, whether before or after retirement. You mentioned two special programs: The Home Buyers' Plan (HBP), and the Lifelong Learning Plan (LLP). Neither the HBP nor the LLP permit tax-free withdrawals. Rather, each of these programs are special kinds of loans that you can borrow from your own RRSP. HBP and LLP loan money isn't taxed when you get it because you are required to pay it back, and you pay it back into your own RRSP: You always pay income tax at your marginal rate on your RRSP withdrawals.** * Above, I said a precise meaning for \"\"retirement\"\" with respect to RRSPs is largely irrelevant. Yet, there are ages that matter: By the end of the year in which you turn 71, you are required to convert your RRSP to a RRIF. It's similar, but you can no longer contribute, and you must withdraw a minimum amount each year. Other circumstances related to age may qualify for minor tax relief intended for retirees, such as the Age Amount or the Pension Income Credit. Generally, such measures don't significantly change the fact that you pay income tax on RRSP withdrawals at your marginal rate – these measures raise the minimum you can take out without attracting tax, but most do nothing at the margin.** ** Exception: One might split eligible pension income with a spouse or common-law partner, which may reduce tax at the margin.\"","title":""},{"docid":"51086","text":"\"The primary tax-sheltered investing vehicles in Canada include: The RRSP. You can contribute up to 18% of your prior year's earned income, up to a limit ($24,930 in 2015, plus past unused contribution allowance) and receive an income tax deduction for your contributions. In an RRSP, investments grow on a tax-deferred basis. No tax is due until you begin withdrawals. When you withdraw funds, the withdrawn amount will be taxed at marginal income tax rates in effect at that time. The RRSP is similar to the U.S. \"\"traditional\"\" IRA, being an individual account with pre-tax contributions, tax-deferred growth, and ordinary tax rates applied to withdrawals. Yet, RRSPs have contribution limits higher than IRAs; higher, even, than U.S. 401(k) employee contribution limits. But, the RRSP is dissimilar to the IRA and 401(k) since an individual's annual contribution allowance isn't use-it-or-lose-it—unused allowance accumulates. The TFSA. Once you turn 18, you can put in up to $5,500 each year, irrespective of earned income. Like the RRSP, contribution room accumulates. If you were 18 in 2009 (when TFSAs were introduced) you'd be able to contribute $36,500 if you'd never contributed to one before. Unlike the RRSP, contributions to a TFSA are made on an after-tax basis and you pay no tax when you withdraw money. The post-tax nature of the TFSA and completely tax-free withdrawals makes them comparable to Roth-type accounts in the U.S.; i.e. while you won't get a tax deduction for contributing, you won't pay tax on earnings when withdrawn. Yet, unlike U.S. Roth-type accounts, you are not required to use the TFSA strictly for retirement savings—there is no penalty for pre-retirement withdrawal of TFSA funds. There are also employer-sponsored defined benefit (DB) and defined contribution (DC) retirement pension plans. Generally, employees who participate in these kinds of plans have their annual RRSP contribution limits reduced. I won't comment on these kinds of plans other than to say they exist and if your employer has one, check it out—many employees lose out on free money by not participating. The under-appreciated RESP. Typically used for education savings. A lifetime $50,000 contribution limit per beneficiary, and you can put that all in at once if you're not concerned about maximizing grants (see below). No tax deduction for contributions, but investments grow on a tax-deferred basis. Original contributions can be withdrawn tax-free. Qualified educational withdrawals of earnings are taxed as regular income in the hands of the beneficiary. An RESP beneficiary is typically a child, and in a child's case the Canadian federal government provides matching grant money (called CESG) of 20% on the first $2500 contributed each year, up to age 18, to a lifetime maximum of $7200 per beneficiary. Grant money is subject to additional conditions for withdrawal. While RESPs are typically used to save for a child's future education, there's nothing stopping an adult from opening an RESP for himself. If you've never had one, you can deposit $50,000 of after-tax money to grow on a tax-deferred basis for up to 36 years ... as far as I understand. An adult RESP will not qualify for CESG. Moreover, if you use the RESP strictly as a tax shelter and don't make qualified educational withdrawals when the time comes, your original contributions still come out free of tax but you'll pay ordinary income tax plus 20% additional tax on the earnings portion. That's the \"\"catch\"\"*. *However, if at that time you have accumulated sufficient RRSP contribution room, you may move up to $50,000 of your RESP earnings into your RRSP without any tax consequences (i.e. also avoiding the 20% additional tax) at time of transfer. Perhaps there's something above you haven't considered. Still, be sure to do your own due diligence and to consult a qualified, experienced, and conflict-free financial advisor for advice particular to your own situation.\"","title":""},{"docid":"451301","text":"\"From Wikipedia - Stock: The stock (also capital stock) of a corporation constitutes the equity stake of its owners. It represents the residual assets of the company that would be due to stockholders after discharge of all senior claims such as secured and unsecured debt. Stockholders' equity cannot be withdrawn from the company in a way that is intended to be detrimental to the company's creditors Wikipedia - Dividend: A dividend is a payment made by a corporation to its shareholders, usually as a distribution of profits. When a corporation earns a profit or surplus, it can re-invest it in the business (called retained earnings), and pay a fraction of this reinvestment as a dividend to shareholders. Distribution to shareholders can be in cash (usually a deposit into a bank account) or, if the corporation has a dividend reinvestment plan, the amount can be paid by the issue of further shares or share repurchase. Wikipedia - Bond: In finance, a bond is an instrument of indebtedness of the bond issuer to the holders. It is a debt security, under which the issuer owes the holders a debt and, depending on the terms of the bond, is obliged to pay them interest (the coupon) and/or to repay the principal at a later date, termed the maturity date. Interest is usually payable at fixed intervals (semiannual, annual, sometimes monthly). Very often the bond is negotiable, i.e. the ownership of the instrument can be transferred in the secondary market. This means that once the transfer agents at the bank medallion stamp the bond, it is highly liquid on the second market. Thus, stock is about ownership in the company, dividends are the payments those owners receive, which may be additional shares or cash usually, and bonds are about lending money. Stocks are usually bought through brokers on various stock exchanges generally. An exception can be made under \"\"Employee Stock Purchase Plans\"\" and other special cases where an employee may be given stock or options that allow the purchase of shares in the company through various plans. This would apply for Canada and the US where I have experience just as a parting note. This is without getting into Convertible Bond that also exists: In finance, a convertible bond or convertible note or convertible debt (or a convertible debenture if it has a maturity of greater than 10 years) is a type of bond that the holder can convert into a specified number of shares of common stock in the issuing company or cash of equal value. It is a hybrid security with debt- and equity-like features. It originated in the mid-19th century, and was used by early speculators such as Jacob Little and Daniel Drew to counter market cornering. Convertible bonds are most often issued by companies with a low credit rating and high growth potential.\"","title":""},{"docid":"27671","text":"\"For an RRSP, you do not have to pay taxes on money or investments until you withdraw the money. If you do not reinvest the dividends but instead, take them out as cash, that would be withdrawing the money. For mutual funds, you would normally reinvest the dividends if holding the investment inside an RRSP. For stocks, I believe the dividends would end up sitting in the cash part of your RRSP account (and you'd probably use the money to buy more stocks, though would not be required to do so). Either way, you do not pay tax on this investment income unless you withdraw it from your RRSP. For example, you invest $10,000 inside your RRSP. You get the tax benefit from doing so. You get dividends of $1,000 (hey, it was a good year), and use these to buy more stock. As the money never left your RRSP account, you are considered to have invested only your initial $10,000. If instead, you withdraw the $1,000 in dividends, you are taxed on $1000 income. TFSA are slightly more complicated. You don't get a tax benefit from your initial contribution, but then do not pay tax when you withdraw from the TFSA. Your investment income is still tax-free, and you are (generally) much more limited in how much you can contribute. For example, you invest $10,000 inside your TFSA. You get dividends of $1,000, and use these to buy more stock. Your total contributions to your TFSA remains at $10,000 as the money never left your account. You could instead withdraw the $1000 from your TFSA and would not pay tax on it. In the next calendar year (or later) after the withdrawal, you could \"\"repay\"\" the $1000 you took out without suffering an overcontribution penalty. This makes TFSA an excellent place to park emergency funds, as you can withdraw and subsequently replace the investment while continuing to get the tax benefits on your investment income. RRSPs are better for retirement or for the home buyers plan. In general, you should not be withdrawing money from either your TFSA or RRSP, except in emergencies, when retiring, or when purchasing a home. I prefer indexed mutual funds or money market accounts for both my RRSP and TFSA rather than individual stocks, but that's up to you.\"","title":""},{"docid":"307832","text":"I don't believe from reading the responses above that Questrade is doing anything 'original' or 'different' much less 'bad'. In RRSPs you are not allowed to go into debt. So the costs of all trades must be covered. If there is not enough USD to pay the bill then enough CAD is converted to do so. What else would anyone expect? How margin accounts work depends on whether the broker sets up different accounts for different currencies. Some do, some don't. The whole point of using 'margin' is to buy securities when you don't have the cash to cover the cost. The result is a 'short' position in the cash. Short positions accrue interest expense which is added to the balance once a month. Every broker does this. If you buy a US stock in a USD account without the cash to cover it, you will end up with USD margin debt. If you buy US stock in an account that co-mingles both USD and CAD assets and cash, then there will be options during the trade asking if you want to settle in USD or CAD. If you settle in CAD then obviously the broker will convert the necessary CAD funds to pay for it. If you settle in US funds, but there is no USD cash in the account, then again, you have created a short position in USD.","title":""},{"docid":"312811","text":"\"Share sales & purchases are accounted only on the balance sheet & cash flow statement although their effects are seen on the income statement. Remember, the balance sheet is like a snapshot in time of all accrued accounts; it's like looking at a glass of water and noting the level. The cash flow and income statements are like looking at the amount of water, \"\"actually\"\" and \"\"imaginary\"\" respectively, pumped in and out of the glass. So, when a corporation starts, it sells shares to whomever. The amount of cash received is accounted for in the investing section of the cash flow statement under the subheading \"\"issuance (retirement) of stock\"\" or the like, so when shares are sold, it is \"\"issuance\"\"; when a company buys back their shares, it's called \"\"retirement\"\", as cash inflows and outflows respectively. If you had a balance sheet before the shares were sold, you'd see under the \"\"equity\"\" heading a subheading common stock with a nominal (irrelevant) par value (this is usually something obnoxiously low like $0.01 per share used for ease of counting the shares from the Dollar amount in the account) under the subaccount almost always called \"\"common stock\"\". If you looked at the balance sheet after the sale, you'd see the number of shares in a note to the side. When shares trade publicly, the corporation usually has very little to do with it unless if they are selling or buying new shares under whatever label such as IPO, secondary offering, share repurchase, etc, but the corporation's volume from such activity would still be far below the activity of the third parties: shares are trading almost exclusively between third parties. These share sales and purchases will only be seen on the income statement under earnings per share (EPS), as EPS will rise and fall with stock repurchases and sales assuming income is held constant. While not technically part of the income statement but printed with it, the \"\"basic weighted average\"\" and \"\"diluted weighted average\"\" number of shares are also printed which are the weighted average over the reporting period of shares actually issued and expected if all promises to issue shares with employee stock options, grants, convertibles were made kept. The income statement is the accrual accounts of the operations of the company. It has little detail on investing (depreciation & appreciation) or financing (interest expenses & preferred dividends).\"","title":""},{"docid":"304085","text":"Any time there is a share adjustment from spin-off, merger, stock split, or reverse slit; there is zero chance for the stockholders to hang on to fractional shares. They are turned into cash. For the employees in the 401K program or investors via a mutual fund or ETF this isn't a problem. Because the fraction of a share left over is compared to the thousands or millions of shares owned by the fund as a collective. For the individual investor in the company this can be a problem that they aren't happy about. In some cases the fractional share is a byproduct that will result from any of these events. In the case of a corporate merger or spin-off most investors will not have an integer number of shares, so that fraction leftover that gets converted to cash isn't a big deal. When they want to boost the price to a specific range to meet a regulatory requirement, they are getting desperate and don't care that some will be forced out. In other cases it is by design to force many shareholders out. They want to go private. They to 1-for-1000 split. If you had less than 1000 shares pre-split then you will end up with zero shares plus cash. They know exactly what number to use. The result after the split is that the number of investors is small enough they they can now fall under a different set of regulations. They have gone dark, they don't have to file as many reports, and they can keep control of the company. Once the Board of Directors or the majority stockholders votes on this, the small investors have no choice.","title":""},{"docid":"433069","text":"I personally spoke with a Questrade agent about my question. To make a long story short: in a margin account, you are automatically issued a loan when buying U.S. stock with a Canadian money. Whereas, in a registered account (e.g. RRSP), the amount is converted on your behalf to cover the debit balance. Me: What happens if I open an account and I place an order for U.S. stocks with Canadian money? Is the amount converted at the time of transfer? How does that work? Agent: In a margin account, you are automatically issued a loan for a currency you do not have, however, if you have enough buying power, it will go through. The interest on the overnight balance is calculated daily and is charged on a monthly basis. We do not convert funds automatically in a margin account because you can have a debit cash balance. Agent: In a registered account, the Canada Revenue Agency does not allow a debit balance and therefore, we must convert your funds on your behalf to cover the debit balance if possible. We convert automatically overnight for a registered account. Agent: For example, if you buy U.S. equity you will need USD to buy it, and if you only have CAD, we will loan you USD to cover for that transaction. For example, if you had only $100 CAD and then wanted to buy U.S. stock worth $100 USD, then we will loan you $100 USD to purchase the stock. In a margin account we will not convert the funds automatically. Therefore, you will remain to have a $100 CAD credit and a $100 USD debit balance (or a loan) in your account. Me: I see, it means the longer I keep the stock, the higher interest will be? Agent: Well, yes, however, in a registered account there will be not be any interest since we convert your funds, but in a margin account, there will be interest until the debit balance is covered, or you can manually convert your funds by contacting us.","title":""},{"docid":"177648","text":"Your first scenario, involving shareholders in a private corp being limited by a contractual agreement, is common in practice. Frequent clauses include methods of valuing the shares if someone wants to sell, first right of refusal [you have to attempt to sell to the other shareholders, before you can sell to a 3rd party], and many others. These clauses are governed by contract law [ie: some clauses may be illegal in contract law, and therefore couldn't be applied here]. A Universal Shareholders' Agreement is just the same as the above, but applied to more people. You would never get an already public company to convert to a universal shareholders' agreement - because even 1 share voting 'no' would block it [due to corporate law limiting the power of a corporation from abusing minority shareholder value]. In practice, these agreements universally exist at the start of incorporation, or at least at the first moment shares become available. An example is the Canadian mega-construction company PCL*, which is employee-owned. When the original owner transferred the corporation to his employees, there was a USA in place which still today governs how the corporation operates. In theory you could have a 'public company' where most shares are already owned by the founders, and 100% of remaining shares are owned by a specific group of individuals, in which case you may be able to get a USA signed. But it wouldn't really happen in practice. *[Note that while PCL is broadly owned by a large group of employees, it is not a 'public company' because any random schmuck can't simply buy a share on the Toronto Stock Exchange. I assume most exchanges would prevent corporations from being listed if they had ownership restrictions like this].","title":""},{"docid":"213767","text":"\"The first 3 are the same as owning stock in a company would be measured in shares and would constitute some percentage of the overall shares outstanding. If there are 100 shares in the company in total, then owning 80 shares is owning 80% is the same as owning 80% of the common stock. This would be the typical ownership case though there can also be \"\"Restricted stock\"\" as something to note here. Convertible debt would likely carry interest charges as well as the choice at the end of becoming stock in the company. In this case, until the conversion is done, the stock isn't issued and thus isn't counted. Taking the above example, one could have a note that could be worth 10 shares but until the conversion is done, the debt is still debt. Some convertible debt could carry options or warrants for the underlying stock as there was the Berkshire convertible notes years ago that carried a negative interest rate that was studied in \"\"The Negative Coupon Bond\"\" if you want an example here. Options would have the right but not the obligation to buy the stock where there are \"\"Incentive Stock Options\"\" to research this in more depth. In this case, one could choose to not exercise the option and thus no stock changes hands. This is where some companies will experience dilution of ownership as employees and management may be given options that put more shares out to the public. Issuing debt wouldn't change the ownership and isn't direct ownership unless the company goes through a restructuring where the creditors become the new stock holders in the case of a Chapter 11 situation in the US. Note that this isn't really investing in a small business as much as it is making a loan to the company that will be paid back in cash. If the company runs into problems then the creditor could try to pursue the assets of the company to be repaid.\"","title":""},{"docid":"19433","text":"I believe your question is based on a false premise. First, no broker, that I know of, provides an RRSP account that is a margin account. RRSP accounts follow cash settlement rules. If you don't have the cash available, you can't buy a stock. You can't borrow money from your broker within your RRSP. If you want to borrow money to invest in your RRSP, you must borrow outside from another source, and make a contribution to your RRSP. And, if you do this, the loan interest is not considered tax deductible. In order for investment loan interest to be tax deductible, you'd need to invest outside of a registered type of account, e.g. using a regular non-tax-sheltered account. Even then, what you can deduct may be limited. Refer to CRA - Line 221 - Carrying charges and interest expenses: You can claim the following carrying charges and interest [...] [...] You cannot deduct on line 221 any of the following amounts:","title":""},{"docid":"161201","text":"Your assumption that funds sold in GBP trade in GBP is incorrect. In general funds purchase their constituent stocks in the fund currency which may be different to the subscription currency. Where the subscription currency is different from the fund currency subscriptions are converted into the fund currency before the extra money is used to increase holdings. An ETF, on the other hand, does not take subscriptions directly but by creation (and redemption) of shares. The principle is the same however; monies received from creation of ETF shares are converted into the fund currency and then used to buy stock. This ensures that only one currency transaction is done. In your specific example the fund currency will be USD so your purchase of the shares (assuming there are no sellers and creation occurs) will be converted from GBP to USD and held in that currency in the fund. The fund then trades entirely in USD to avoid currency risk. When you want to sell your exposure (supposing redemption occurs) enough holdings required to redeem your money are sold to get cash in USD and then converted to GBP before paying you. This means that trading activity where there is no need to convert to GBP (or any other currency) does not incur currency conversion costs. In practice funds will always have some cash (or cash equivalents) on hand to pay out redemptions and will have an idea of the number and size of redemptions each calendar period so will use futures and swaps to mitigate FX risk. Where the same firm has two funds traded in different currencies with the same objectives it is likely that one is a wrapper for the other such that one simply converts the currency and buys the other currency denominated ETF. As these are exchange traded funds with a price in GBP the amount you pay for the ETF or gain on selling it is the price given and you will not have to consider currency exchange as that should be done internally as explained above. However, there can be a (temporary) arbitrage opportunity if the price in GBP does not reflect the price in USD and the exchange rate put together.","title":""},{"docid":"589127","text":"\"There are more than a few different ways to consider why someone may have a transaction in the stock market: Employee stock options - If part of my compensation comes from having options that vest over time, I may well sell shares at various points because I don't want so much of my new worth tied up in one company stock. Thus, some transactions may happen from people cashing out stock options. Shorting stocks - This is where one would sell borrowed stock that then gets replaced later. Thus, one could reverse the traditional buy and sell order in which case the buy is done to close the position rather than open one. Convertible debt - Some companies may have debt that come with warrants or options that allow the holder to acquire shares at a specific price. This would be similar to 1 in some ways though the holder may be a mutual fund or company in some cases. There is also some people that may seek high-yield stocks and want an income stream from the stock while others may just want capital appreciation and like stocks that may not pay dividends(Berkshire Hathaway being the classic example here). Others may be traders believing the stock will move one way or another in the short-term and want to profit from that. So, thus the stock market isn't necessarily as simple as you state initially. A terrorist attack may impact stocks in a couple ways to consider: Liquidity - In the case of the attacks of 9/11, the stock market was closed for a number of days which meant people couldn't trade to convert shares to cash or cash to shares. Thus, some people may pull out of the market out of fear of their money being \"\"locked up\"\" when they need to access it. If someone is retired and expects to get $x/quarter from their stocks and it appears that that may be in jeopardy, it could cause one to shift their asset allocation. Future profits - Some companies may have costs to rebuild offices and other losses that could put a temporary dent in profits. If there is a company that makes widgets and the factory is attacked, the company may have to stop making widgets for a while which would impact earnings, no? There can also be the perception that an attack is \"\"just the beginning\"\" and one could extrapolate out more attacks that may affect broader areas. Sometimes what recently happens with the stock market is expected to continue that can be dangerous as some people may believe the market has to continue like the recent past as that is how they think the future will be.\"","title":""},{"docid":"525390","text":"\"A company has 100,000 shares and 100,000 unexercised call options (company issued). Share price and strike price both at $1. What country is this related to? I ask because, in the US, most people I know associate a \"\"call\"\" option with the instrument that is equivalent to 100 shares. So 100,000 calls would be 10,000,000 shares, which exceeds the number of shares you're saying the company has. I don't know if that means you pulled the numbers out of thin air, or whether it means you're thinking of a different type of option? Perhaps you meant incentive stock options meant to be given to employees? Each one of those is equivalent to a single share. They just aren't called \"\"call options\"\". In the rest of my answer, I'm going to assume you meant stock options. I assume the fact that these options exist will slow any price increases on the underlying shares due to potential dilution? I don't think the company can just create stock options without creating the underlying shares in the first place. Said another way, a more likely scenario is that company creates 200,000 shares and agrees to float 50% of them while reserving the other 50% as the pool for incentive employee stock. They then choose to give the employees options on the stock in the incentive pool, rather than outright grants of the stock, for various reasons. (One of which is being nice to the employees in regards to taxes since there is no US tax due at grant time if the strike price is the current price of the underlying stock.) An alternative scenario when the company shares are liquidly traded is that the company simply plans to buy back shares from the market in order to give employees their shares when options are exercised. In this case, the company needs the cash on hand, or cash flow to take money from, to buy those shares at current prices. Anyway, in either case, there is no dilution happening WHEN the options get exercised. Any dilution happened before or at the time the options were created. Meaning, the total number of shares in the company was already pre-set at an earlier time. As a result, the fact that the options exist in themselves will not slow price changes on the stock. However, price changes will be impacted by the total float of shares in the company, or the impact to cash flow if the company has to buy shares to redeem its option commitments. This is almost the same thing you're asking about, but it is technically different as to timing. If this is the case, can this be factored into any option pricing models like black-scholes? You're including the effect just by considering the total float of shares and net profits from cash flow when doing your modelling.\"","title":""},{"docid":"76530","text":"\"All transactions within an IRA are irrelevant as far as the taxation of the distributions from the IRA are concerned. You can only take cash from an IRA, and a (cash) distribution from a Traditional IRA is taxable as ordinary income (same as interest from a bank, say) without the advantage of any of the special tax rates for long-term capital gains or qualified dividends even if that cash was generated within the IRA from sales of stock etc. In short, just as with what is alleged to occur with respect to Las Vegas, what happens within the IRA stays within the IRA. Note: some IRA custodians are willing to make a distribution of stock or mutual fund shares to you, so that ownership of the 100 shares of GE, say, that you hold within your IRA is transferred to you in your personal (non-IRA) brokerage account. But, as far as the IRS is concerned, your IRA custodian sold the stock as the closing price on the day of the distribution, gave you the cash, and you promptly bought the 100 shares (at the closing price) in your personal brokerage account with the cash that you received from the IRA. It is just that your custodian saved the transaction fees involved in selling 100 shares of GE stock inside the IRA and you saved the transaction fee for buying 100 shares of GE stock in your personal brokerage account. Your basis in the 100 shares of GE stock is the \"\"cash_ that you imputedly received as a distribution from the IRA, so that when you sell the shares at some future time, your capital gains (or losses) will be with respect to this basis. The capital gains that occurred within the IRA when the shares were imputedly sold by your IRA custodian remain within the IRA, and you don't get to pay taxes on that at capital gains rates. That being said, I would like to add to what NathanL told you in his answer. Your mother passed away in 2011 and you are now 60 years old (so 54 or 55 in 2011?). It is likely that your mother was over 70.5 years old when she passed away, and so she likely had started taking Required Minimum Distributions from her IRA before her death. So, You should have been taking RMDs from the Inherited IRA starting with Year 2012. (The RMD for 2011, if not taken already by your mother before she passed away, should have been taken by her estate, and distributed to her heirs in accordance with her will, or, if she died intestate, in accordance with state law and/or probate court directives). There would not have been any 10% penalty tax due on the RMDs taken by you on the grounds that you were not 59.5 years old as yet; that rule applies to owners (your mom in this case) and not to beneficiaries (you in this case). So, have you taken the RMDs for 2012-2016? Or were you waiting to turn 59.5 before taking distributions in the mistaken belief that you would have to pay a 10% penalty for early wthdrawal? The penalty for not taking a RMD is 50% of the amount not distributed; yes, 50%. If you didn't take RMDs from the Inherited IRA for years 2012-2016, I recommend that you consult a CPA with expertise in tax law. Ask the CPA if he/she is an Enrolled Agent with the IRS: Enrolled Agents have to pass an exam administered by the IRS to show that they really understand tax law and are not just blowing smoke, and can represent you in front of the IRS in cases of audit etc,\"","title":""},{"docid":"212783","text":"\"Federal taxes are generally lower in Canada. Canada's top federal income tax rate is 29%; the US rate is 35% and will go to 39.6% when Bush tax cuts expire. The healthcare surcharge will kick in in a few years, pushing the top bracket by a few more points and over 40%. State/provincial taxes are lower in the US. You may end up in the 12% bracket in New York City or around 10% in California or other \"\"bad\"\" income-tax states. But Alberta is considered a tax haven in Canada and has a 10% flat tax. Ontario's top rate is about 11%, but there are surtaxes that can push the effective rate to about 17%. Investment income taxes: Canada wins, narrowly. Income from capital gains counts as half, so if you're very rich and live in Ontario, your rate is about 23% and less than that in Alberta. The only way to match or beat this deal in the US in the long term is to live in a no-income-tax state. Dividends are taxed at rates somewhere between capital gains and ordinary income - not as good a deal as Bush's 15% rate on preferred dividends, but that 15% rate will probably expire soon. Sales taxes: US wins, but the gap is closing. Canada has a national VAT-like tax, called GST and its rate came down from 7% to 5% when Harper became the Prime Minister. Provinces have sales taxes on top of that, in the range of 7-8% (but Alberta has no sales tax). Some provinces \"\"harmonized\"\" their sales taxes with the GST and charge a single rate, e.g. Ontario has a harmonized sales tax (HST) of 13% (5+8). 13% is of course a worse rate than the 6-8% charged by most states, but then some states and counties already charge 10% and the rates have been going up in each recession. Payroll taxes: much lower in Canada. Canadian employees' CPP and EI deductions have a low threshold and top out at about $3,000. Americans' 7.65% FICA rate applies to even $100K, resulting in a tax of $7,650. Property taxes: too dependent on the location, hard to tell. Tax benefits for retirement savings: Canada. If you work in the US and don't have a 401(k), you get a really bad deal: your retirement is underfunded and you're stuck with a higher tax bill, because you can't get the deduction. In Canada, if you don't have an RRSP at work, you take the money to the financial company of your choice, invest it there, and take the deduction on your taxes. If you don't like the investment options in your 401(k), you're stuck with them. If you don't like them in your RRSP, contribute the minimum to get the match and put the rest of the money into your individual RRSP; you still get the same deduction. Annual 401(k) contribution limits are use-it-or-lose-it, while unused RRSP limits and deductions can be carried forward and used when you need to jump tax brackets. Canada used to lack an answer to Roth IRAs, but the introduction of TFSAs took care of that. Mortgage interest deduction: US wins here as mortgage interest is not deductible in Canada. Marriage penalty: US wins. Canadian tax returns are of single or married-filing-separately type. So if you have one working spouse in the family or a big disparity between spouses' incomes, you can save money by filing a joint return. But such option is not available in Canada (there are ways to transfer some income between spouses and fund spousal retirement accounts, but if the income disparity is big, that won't be enough). Higher education: cheaper in Canada. This is not a tax item, but it's a big expense for many families and something the government can do about with your tax dollars. To sum it up, you may face higher or lower or about the same taxes after moving from US to Canada, depending on your circumstances. Another message here is that the high-tax, socialist, investment-unfriendly Canada is mostly a convenient myth.\"","title":""},{"docid":"442741","text":"You don't seem to have any particular question to be answered. Your understanding of RRSPs seems to be very good. Have you considered whether you might be better off putting your retirement savings into a TFSA instead? Both types can protect your growth from taxation (provided you reinvest the refund from the RRSP). The main way in which the RRSP is better than TFSA is that you can pay the tax on the contribution at a time when your income is lower, and thus have a lower marginal tax rate. Most people retire with a lower income than during their earning years, but it's a matter of tax brackets. If you think you'll be in the same bracket (same marginal tax rate) when you retire, then the TFSA and RRSP work out even in that regard. So in your case, the question you want to ask yourself is: when I retire, will I have an income (including CPP, OAS, pension payments, etc) that exceeds $45,282 worth of today's dollars? If so, your RRSP holds no advantage over the TFSA. In fact, the RRSP may even be worse, since the withdrawals count as income and reduce the amount of OAS and perhaps GIS payments that the government gives you - at least under current regulations. If you're unsure, I suggest you try this calculator from taxtips.ca that runs both scenarios and helps you see which one is more beneficial. It even factors in the OAS/GIS clawbacks.","title":""},{"docid":"12899","text":"Full disclosure: I’m an intern for EquityZen, so I’m familiar with this space but can speak with the most accuracy about EquityZen. Observations about other players in the space are my own. The employee liquidity landscape is evolving. EquityZen and Equidate help shareholders (employees, ex-employees, etc.) in private companies get liquidity for shares they already own. ESOFund and 137 Ventures help with option financing, and provide loans (and exotic structures on loans) to cover costs of exercising options and any associated tax hit. EquityZen is a private company marketplace that led the second wave of VC-backed secondary markets starting early 2013. The mission is to help achieve liquidity for employees and other private company shareholder, but in a company-approved way. EquityZen transacts with share transfers and also a proprietary derivative structure which transfers economics of a company's shares without changing voting and information rights. This structure typically makes the transfer process cheaper and faster as less paperwork is involved. Accredited investors find the process appealing because they get access to companies they usually cannot with small check sizes. To address the questions in Dzt's post: 1). EquityZen doesn't take a 'loan shark' approach meaning they don't front shareholders money so that they can purchase their stock. With EquityZen, you’re either selling your shares or selling all the economic risk—upside and downside—in exchange for today’s value. 2). EquityZen only allows company approved deals on the platform. As a result, companies are more friendly towards the process and they tend to allow these deals to take place. Non-company approved deals pose risks for buyers and sellers and are ultimately unsustainable. As a buyer, without company blessing, you’re taking on significant counterparty risk from the seller (will they make good on their promise to deliver shares in the future?) or the risk that the transfer is impermissible under relevant restrictions and your purchase is invalid. As a seller, you’re running the risk of violating your equity agreements, which can have severe penalties, like forfeiture of your stock. Your shares are also much less marketable when you’re looking to transact without the company’s knowledge or approval. 3). Terms don't change depending an a shareholder's situation. EquityZen is a professional company and values all of the shareholders that use the platform. It’s a marketplace so the market sets the price. In other situations, you may be at the mercy of just one large buyer. This can happen when you’re facing a big tax bill on exercise but don’t have the cash (because you have the stock). 4). EquityZen doesn't offer loans so this is a non issue. 5). Not EquityZen! EquityZen creates a clean break from the economics. It’s not uncommon for the loan structures to use an interest component as well as some other complications, like upside participation and and also a liquidation preference. EquityZen strives for a simple structure where you’re not on the hook for the downside and you’ve transferred all the upside as well.","title":""},{"docid":"331268","text":"The term self-directed generally refers to RRSP accounts where the account holder has not only the ability to determine a basic investment asset mix (such as can be accomplished even with a limited selection of mutual funds) but, more specifically, the self-directed account holder has a much wider choice of financial instruments beyond mutual funds, GICs, and/or cash savings. A self-directed RRSP generally permits the account holder to also invest or trade directly in financial instruments such as: Those kinds of instruments are not typically available in a non-self-directed mutual fund or bank RRSP. Typical mutual fund or bank RRSPs offer you only their choice of products – often with higher fees attached. Related resources:","title":""},{"docid":"17208","text":"See my comment for some discussion of why one might choose an identical fund over an ETF. As to why someone would choose the higher cost fund in this instance ... The Admiral Shares version of the fund (VFIAX) has the same expense ratio as the ETF but has a minimum investment of $10K. Some investors may want to eventually own the Admiral Shares fund but do not yet have $10K. If they begin with the Investor Shares now and then convert to Admiral later, that conversion will be a non-taxable event. If, however, they start with ETF shares now and then sell them later to buy the fund, that sale will be a taxable event. Vanguard ETFs are only commission-free to Vanguard clients using Vanguard Brokerage Services. Some investors using other brokers may face all sorts of penalties for purchasing third-party ETFs. Some retirement plan participants (either at Vanguard or another broker) may not even be allowed to purchase ETFs.","title":""},{"docid":"103842","text":"Does the 5 year rule apply on the After-tax 401k -> Roth 401k -> Roth IRA conversion of the 20000 (including 10000 earnings that was originally pre-tax)? No. The after-tax amounts are not subject to the 5 years rule. The earnings are. How does this affect Roth IRA withdrawal ordering rules with respect to the taxable portion of a single conversion being withdrawn before the non-taxable portion? Taxable portion first until exhausted. To better understand how it works, you need to understand the rationale behind the 5-year rule. Consider you have $100K in your IRA (traditional) and you want to take it out. Just withdrawing it would trigger a 10K statutory penalty, on top of the taxes due. But, you can use the backdoor Roth IRA, right? So convert the 100K, and then it becomes after-tax contribution to Roth IRA, and can be withdrawn with no penalty. One form filled ad 10K saved. To block this loophole, here comes the 5 years rule: you cannot withdraw after-tax amounts for at least 5 years without penalty, if the source was taxable conversion. Thus, in order to avoid the 10K penalty in the above situation, you have a 5-year cooling period, which makes the loophole useless for most cases. However amounts that are after tax can be withdrawn without penalty already, even from the traditional IRA, so there's no need in the 5 years cooling period. The withdrawal attribution is in this order: Roth IRA rollovers are sourced to the origin. E.g.: if you converted $100 to the Roth IRA at firm X and then a year later rolled it over to firm Y - it doesn't affect anything and the clock is ticking from the original date of the conversion at firm X. 5-year period applies to each conversion/rollover from a qualified retirement plan (see here). Distributions are applied to the conversions in FIFO order, so in one distribution, depending on the amounts, you may hit several different incoming conversions. The 5 years should be check on each of them, and the penalty applied on the amounts attributable to those that don't have enough time. 5-year period for contributions applies starting from the beginning of the first year of the first contribution that established your Roth IRA plan. The penalty applies to the amounts that were included in your gross income when conversion occurred, i.e.: doesn't apply on the amounts converted from after-tax sources. Note the difference from the traditional IRA - distributions from pre-tax sources are prorated between the non-deductible (basis) amounts and the deductible/earnings amounts (taxable). That is why the taxable amounts are first in the ordering of the distributions.","title":""},{"docid":"481169","text":"Firstly a stock split is easy, for example each unit of stock is converted into 10 units. So if you owned 1% of the company before the stock split, you will still own 1% after the stock split, but have 10 times the number of shares. The company does not pay out any money when doing this and there is no effect on tax for the company or the share holder. Now onto stock dividend… When a company make a profit, the company gives some of the profit to the share holders as a dividend; this is normally paid in cash. An investor may then wish to buy more shares in the company using the money from the dividend. However buying shares used to have a large cost in broker charges etc. Therefore some companies allowed share holders to choose to have the dividend paid as shares. The company buys enough of their own shares to cover the payout, only having one set of broker charges and then sends the correct number of shares to each share holder that has opted for a stock dividend. (Along with any cash that was not enough to buy a complete share.) This made since when you had paper shares and admin costs where high for stock brokers. It does not make sense these days. A stock dividend is taxed as if you had been paid the dividend in cash and then brought the stock yourself.","title":""},{"docid":"88539","text":"There are two significant drawbacks to this type of transfer. They were the reasons why I kept my American 401(k) as-is and started funding my Canadian RRSP from zero balance. 1. Taxes - a large chunk of your 401(k) will be lost to taxes. There is probably no way to transfer the funds without making a 401(k)/IRA withdrawal, which will incur the US federal tax and the 10% early-withdrawal penalty. When the money went into the 401(k), you got a tax deduction in the US and the tax break is supposed be repaid later when you make a withdrawal (that's basically how tax deferral works). It's unlikely that any country will let you take a deduction first and send the payback to a foreign country. The withdrawal amount may also be taxable in Canada (Canadians generally pay taxes on their global income and that includes pensions and distributions from foreign retirement plans). Foreign tax credit will apply of course, to eliminate double taxation, but it's of little help if your marginal Canadian tax rate is higher than your average US tax rate. 2. Expenses. Your RRSP will have to be invested in something and mutual fund management expenses are generally higher in Canada than in the US. For example, my employer-sponsored RRSP has a Standard & Poor's stock index fund that charges 1.5% and that is considered low-cost. It also offers a number of managed funds with expenses in excess of 2% that I simply ignore. You can probably invest your American 401(k)/IRA in mutual funds more efficiently.","title":""},{"docid":"394734","text":"Employees were already cashing out their RSUs and selling stock on private markets. >Even if Facebook could resist, an eager army of Facebook employees is pushing hard for an I.P.O., according to Eric Eldon of TechCrunch. In 2008, Facebook adopted a new restricted stock program that prevented employees from selling their shares until an I.P.O. or a sale, or if Facebook permitted it. They still could have stayed private if they really wanted to. They were compensating employees in stock, and those employees wanted to cash out. The underwriters wanted to cash out before the financials became open to public scrutiny.","title":""},{"docid":"152049","text":"\"I have some money invested on Merrill Edge. 2 days ago I purchased some mutual funds with most of the rest of my money in my account. I logged in today to see how it did, and noticed that there are 3 sections: Priced Investments, Cash & Money Accounts, and Pending Activity. In the Cash & Money section, there shows a negative balance of Cash (let's say -$1,000) and a positive \"\"Money Account Value\"\" (let's say +$1,100). The \"\"Money Account\"\" appears to be made up of $1 shares of something called \"\"ML Direct Deposit Program\"\". However, even though the mutual fund purchase was made 2 days ago, and the shares of the mutual funds are officially in my account, I'm still showing all of my \"\"Money Account\"\" shares ($1000). The balance sheet effectively makes it look like I somehow needed to have \"\"sold\"\" back my money account shares, converted them to cash, and then bought the funds. I'm hoping that isn't the case, and for some reason, there is a multiday lag between me buying stock and money getting deducted from my \"\"Money Account\"\". Hope that all makes sense. TLDR: what's the diff between a Cash account and Money Account that's filled with shares of \"\" ML Direct Deposit Program\"\"? Edit: Today the cash and money account offset by equal values equal to one of my mutual fund purchases.\"","title":""},{"docid":"312679","text":"Here's the best explanation I found relating to why your T4 box 39 might not have an amount filled in, even when box 38 has one: Department of Finance – Explanatory Notes Relating to the Income Tax Act [...]. It's a long document, but here's the part I believe relevant, with my emphasis: Employee Stock Options ITA 110(1) [...] Paragraph 110(1)(d) is amended to include a requirement that the employee [...] exercise the employee’s rights under the stock option agreement and acquire the securities underlying the agreement in order for the deduction in computing taxable income to be available [...] ensures that only one deduction is available in respect of an employment benefit. In other words, if employee stock option rights are surrendered to an employer for cash or an in-kind payment, then (subject to new subsections 110(1.1) and (1.2)) the employer may deduct the payment but the employee cannot claim the stock option deduction. Conversely, where an employer issues securities pursuant to an employee’s exercise of stock options, the employer can not deduct an amount in respect of the issuance, but the employee may be eligible to claim a deduction under paragraph 110(1)(d). Did you receive real shares based on your participation in the ESPP, or did you get a cash payment for the net value of shares you would have been issued under the plan? From what I can tell, if you opted for a cash payment (or if your plan only allows for such), then the part I emphasized comes into play. Essentially, if conditions were such that your employer could claim a deduction on their corporate income tax return for the compensation paid to you as part of the plan, then you are not also able to claim a similar deduction on your personal income tax return. The money received in that manner is effectively taxed in your hands the same as any bonus employment income would be; i.e. it isn't afforded tax treatment equivalent to capital gains income. Your employer and/or ESPP administrator are best able to confirm the conditions which led to no amount in your box 39, but at least based on above you can see there are legitimate cases where box 38 would have an amount while box 39 doesn't.","title":""},{"docid":"127958","text":"I think you are having trouble understanding what 'liquid' means. Liquidity refers to how easily an asset can be converted to cash. More liquid = more easily converted to cash, less liquid, less so. Any kind of exit load is going to make an asset less liquid due to the penalties associated with making the sale. So, the whole point of liquid funds is to give people the option of selling quickly if they need to. Since an exit load is meant to discourage this behavior, liquid funds tend not to have one. The point isn't what the financial institution 'gets', it's about offering a service to clients with a particular investment need.","title":""},{"docid":"444568","text":"There are some great answers on this site similar to what you asked, with either a non-jurisdictional or a US-centric focus. I would read those answers as well to give yourself more points of view on early investing. There are a few differences between Canada and the US from an investing perspective that you should also then consider, namely tax rules, healthcare, and education. I'll get Healthcare and Education out of the way quickly. Just note the difference in perspective in Canada of having government healthcare; putting money into health-savings plans or focusing on insurance as a workplace benefit is not a key motivating factor, but more a 'nice-to-have'. For education, it is more common in Canada for a student to either pay for school while working summer / part-time jobs, or at least taking on manageable levels of debt [because it is typically not quite as expensive as private colleges in the US]. There is still somewhat of a culture of saving for your child's education here, but it is not as much of a necessity as it may be in the US. From an investing perspective, I will quickly note some common [though not universal] general advice, before getting Canadian specific. I have blatantly stolen the meat of this section from Ben Miller's great answer here: Oversimplify it for me: the correct order of investing Once you have a solid financial footing, some peculiarities of Canadian investing are below. For all the tax-specific plans I'm about to mention, note that the banks do a very good job here of tricking you into believing they are complex, and that you need your hand to be held. I have gotten some criminally bad tax advice from banking reps, so at the risk of sounding prejudiced, I recommend that you learn everything you can beforehand, and only go into your bank when you already know the right answer. The 'account types' themselves just involve a few pages of paperwork to open, and the banks will often do that for free. They make up their fees in offering investment types that earn them management fees once the accounts are created. Be sure to separate the investments (stocks vs bonds etc.) vs the investment vehicles. Canada has 'Tax Free Savings Accounts', where you can contribute a certain amount of money every year, and invest in just about anything you want, from bonds to stocks to mutual funds. Any Income you earn in this account is completely tax free. You can withdraw these investments any time you want, but you can't re-contribute until January 1st of next year. ie: you invest $5k today in stocks held in a TFSA, and they grow to $6k. You withdraw $6k in July. No tax is involved. On January 1st next year, you can re-contribute a new $6K, and also any additional amounts added to your total limit annually. TFSA's are good for short-term liquid investments. If you don't know for sure when you'll need the money, putting it in a TFSA saves you some tax, but doesn't commit you to any specific plan of action. Registered Retirement Savings Plans allow you to contribute money based on your employment income accrued over your lifetime in Canada. The contributions are deducted from your taxable income in the year you make them. When you withdraw money from your RRSP, the amount you withdraw gets added as additional income in that year. ie: you invest $5k today in stocks held in an RRSP, and get a $5k deduction from your taxable income this year. The investments grow to $6k. You withdraw $6k next year. Your taxable income increases by $6k [note that if the investments were held 'normally' {outside of an RRSP}, you would have a taxable gain of only 50% of the total gain; but withdrawing the amount from your RRSP makes the gain 100% taxable]. On January 1st next year, you CANNOT recontribute this amount. Once withdrawn, it cannot be recontributed [except for below items]. RRSP's are good for long-term investing for retirement. There are a few factors at play here: (1) you get an immediate tax deduction, thus increasing the original size of investment by deferring tax to the withdrawal date; (2) your investments compound tax-free [you only pay tax at the end when you withdraw, not annually on earnings]; and (3) many people expect that they will have a lower tax-rate when they retire, than they do today. Some warnings about RRSP's: (1) They are less liquid than TFSA's; you can't put money in, take it out, and put it in again. In general, when you take it out, it's out, and therefore useless unless you leave it in for a long time; (2) Income gets re-characterized to be fully taxable [no dividend tax credits, no reduced capital gains tax rate]; and (3) There is no guarantee that your tax rate on retirement will be less than today. If you contribute only when your tax rate is in the top bracket, then this is a good bet, but even still, in 30 years, tax rates might rise by 20% [who knows?], meaning you could end up paying more tax on the back-end, than you saved in the short term. Home Buyer Plan RRSP withdrawals My single favourite piece of advice for young Canadians is this: if you contribute to an RRSP at least 3 months before you make a down payment on your first house, you can withdraw up to $25k from your RRSP without paying tax! to use for the down payment. Then over the next ~10 years, you need to recontribute money back to your RRSP, and you will ultimately be taxed when you finally take the money out at retirement. This means that contributing up to 25k to an RRSP can multiply your savings available for a down payment, by the amount of your tax rate. So if you make ~60k, you'll save ~35% on your 25k deposited, turning your down payment into $33,750. Getting immediate access to the tax savings while also having access to the cash for a downpayment, makes the Home Buyer Plan a solid way to make the most out of your RRSP, as long as one of your near-term goals is to own your own home. Registered Pension Plans are even less liquid than RRSPs. Tax-wise, they basically work the same: you get a deduction in the year you contribute, and are taxed when you withdraw. The big difference is that there are rules on when you are allowed to withdraw: only in retirement [barring specific circumstances]. Typically your employer's matching program (if you have one) will be inside of an RPP. Note that RPP's and RRSP's reduce your taxes on your employment paycheques immediately, if you contribute through a work program. That means you get the tax savings during the year, instead of all at once a year later on April 30th. *Note that I have attempted at all times to keep my advice current with applicable tax legislation, but I do not guarantee accuracy. Research these things yourself because I may have missed something relevant to your situation, I may be just plain wrong, and tax law may have changed since I wrote this to when you read it.","title":""},{"docid":"399932","text":"As a rule of thumb, no. Only in very rare circumstances will it prove better than a RRSP. The media has overplayed the usefulness of this account type for retirement savings. That's just a general rule. Your specific situation will make a difference but it's very easy to show that RRSPs will always outperform if the marginal rates are lower on withdrawal than when you deduct contributions from income. If you plan to use the money before retirement or you're expecting to collect GIS on retirement then you may need to look at the specifics of your situation. If you plan to put money in a RRSP and carry forward the deduction to use at a later date then it doesn't matter whether you put it in a RRSP now or use the TFSA and transfer it later. The RRSP also has advantages of some tax treaties and creditor protection. It (as a RRIF) can also be used after 65 for income splitting and the pension credit. An RESP can also provide a greater return as you get free money, which is always good. There are many other things you can do with it but I'd say it's always better in a TFSA than paying tax in a regular account. Since you pay the mortgage with after tax dollars that could be another option for the cash and it's a guaranteed return, albeit small nowadays.","title":""},{"docid":"68609","text":"\"I was told if I moved my 401k into a Roth IRA that school purposes is one reasons you can withdraw money without having to pay a tax. Incorrect. You will need to pay tax on the amount converted, since a 401(k) is pre-tax and a Roth IRA is after-tax. It will be added to your regular income, so you will pay tax at your marginal tax rate. is there any hidden tax or fee at all for withdrawing money from a Roth IRA for educational purposes? You still will need to pay the tax on the amount converted, but you'll avoid the 10% penalty for early withdrawal. I know that tuition, books and fees are covered for educational purposes. Can I take out of my Roth IRA for living expenses while I'm attending school? Rent, gas, food, etc... Room and board, yes, so long as you are half-time, but not gas/food Possibly only room and board for staying on-campus, but I'm not certain, although I doubt you could call your normal house payment \"\"education expense\"\" with my 401k being smaller, would it just be better to go ahead and cash the whole thing and just pay the tax and use it for whatever I need it for? What is the tax if I just decide to cash the whole thing in? You pay your marginal tax rate PLUS a 10% penalty for early withdrawal. So no, this is probably not a wise move financially unless you're on the verge of bankruptcy or foreclosure (where distress costs are much higher then the 10% penalty) I can't answer the other questions regarding grants; I would talk to the financial aid department at your school. Bottom line, transferring your 401(k) is very likely a bad idea unless you can afford to pay the tax in cash (meaning without borrowing). My advice would be to leave your 401(k) alone (it's meant for retirement not for school or living expenses) Ideally, you should pay for as much as you can out of cash flow, and don't take out more student loans. That may mean taking fewer classes, getting another part time job, finding a different (cheaper) school, applying for more grants and scholarships, etc. I would not in ANY circumstance cash out your 401(k) to pay for school. You'll be much worse off in the long run, and there are much cheaper ways to get money.\"","title":""}],"string":"[\n {\n \"docid\": \"432902\",\n \"text\": \"\\\"Your question is based on incorrect assumptions. Generally, there's no \\\"\\\"penalty\\\"\\\", per se, to make a withdrawal from your RRSP, even if you make a withdrawal earlier than retirement, however you define it. A precise meaning for \\\"\\\"retirement\\\"\\\" with respect to RRSPs is largely irrelevant.* Our U.S. neighbours have a 10% penalty on non-hardship early withdrawals (before age 59 ½) from retirement accounts like the 401k and IRA. It's an additional measure designed to discourage early withdrawals, and raise more tax. Yet, in Canada, there is no similar penalty. Individual investments inside your RRSP may have associated penalties, such as the dreaded \\\"\\\"deferred sales charge\\\"\\\" (DSC) of some back-end loaded mutual funds, or such as LSVCC funds that generated additional special tax credits that could get clawed back. Yet, these early withdrawal penalties are distinct from the RRSP nature of your account. Choose your investments carefully to avoid these kinds of surprises. Rather, an RRSP is a tax-deferred account, and it works like this: The government allows you to claim a nice juicy tax deduction, which can reduce your income tax at your marginal rate in the year you make a contribution, or later if you should choose to defer the deduction. The resulting pre-tax money accumulated in your RRSP benefits from further tax deferral: assets can grow without attracting annual income tax on earned interest, dividends, or capital gains. You don't need to declare on your income tax return any of the income earned inside your RRSP, unlike a regular investment account. Here's the rub: Once you decide to withdraw money from your RRSP, the entire amount withdrawn is considered regular income in the year in which you make the withdrawal. Thus, your withdrawals are subject to income tax, and yes, at your marginal rate. This is always the case, whether before or after retirement. You mentioned two special programs: The Home Buyers' Plan (HBP), and the Lifelong Learning Plan (LLP). Neither the HBP nor the LLP permit tax-free withdrawals. Rather, each of these programs are special kinds of loans that you can borrow from your own RRSP. HBP and LLP loan money isn't taxed when you get it because you are required to pay it back, and you pay it back into your own RRSP: You always pay income tax at your marginal rate on your RRSP withdrawals.** * Above, I said a precise meaning for \\\"\\\"retirement\\\"\\\" with respect to RRSPs is largely irrelevant. Yet, there are ages that matter: By the end of the year in which you turn 71, you are required to convert your RRSP to a RRIF. It's similar, but you can no longer contribute, and you must withdraw a minimum amount each year. Other circumstances related to age may qualify for minor tax relief intended for retirees, such as the Age Amount or the Pension Income Credit. Generally, such measures don't significantly change the fact that you pay income tax on RRSP withdrawals at your marginal rate – these measures raise the minimum you can take out without attracting tax, but most do nothing at the margin.** ** Exception: One might split eligible pension income with a spouse or common-law partner, which may reduce tax at the margin.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"51086\",\n \"text\": \"\\\"The primary tax-sheltered investing vehicles in Canada include: The RRSP. You can contribute up to 18% of your prior year's earned income, up to a limit ($24,930 in 2015, plus past unused contribution allowance) and receive an income tax deduction for your contributions. In an RRSP, investments grow on a tax-deferred basis. No tax is due until you begin withdrawals. When you withdraw funds, the withdrawn amount will be taxed at marginal income tax rates in effect at that time. The RRSP is similar to the U.S. \\\"\\\"traditional\\\"\\\" IRA, being an individual account with pre-tax contributions, tax-deferred growth, and ordinary tax rates applied to withdrawals. Yet, RRSPs have contribution limits higher than IRAs; higher, even, than U.S. 401(k) employee contribution limits. But, the RRSP is dissimilar to the IRA and 401(k) since an individual's annual contribution allowance isn't use-it-or-lose-it—unused allowance accumulates. The TFSA. Once you turn 18, you can put in up to $5,500 each year, irrespective of earned income. Like the RRSP, contribution room accumulates. If you were 18 in 2009 (when TFSAs were introduced) you'd be able to contribute $36,500 if you'd never contributed to one before. Unlike the RRSP, contributions to a TFSA are made on an after-tax basis and you pay no tax when you withdraw money. The post-tax nature of the TFSA and completely tax-free withdrawals makes them comparable to Roth-type accounts in the U.S.; i.e. while you won't get a tax deduction for contributing, you won't pay tax on earnings when withdrawn. Yet, unlike U.S. Roth-type accounts, you are not required to use the TFSA strictly for retirement savings—there is no penalty for pre-retirement withdrawal of TFSA funds. There are also employer-sponsored defined benefit (DB) and defined contribution (DC) retirement pension plans. Generally, employees who participate in these kinds of plans have their annual RRSP contribution limits reduced. I won't comment on these kinds of plans other than to say they exist and if your employer has one, check it out—many employees lose out on free money by not participating. The under-appreciated RESP. Typically used for education savings. A lifetime $50,000 contribution limit per beneficiary, and you can put that all in at once if you're not concerned about maximizing grants (see below). No tax deduction for contributions, but investments grow on a tax-deferred basis. Original contributions can be withdrawn tax-free. Qualified educational withdrawals of earnings are taxed as regular income in the hands of the beneficiary. An RESP beneficiary is typically a child, and in a child's case the Canadian federal government provides matching grant money (called CESG) of 20% on the first $2500 contributed each year, up to age 18, to a lifetime maximum of $7200 per beneficiary. Grant money is subject to additional conditions for withdrawal. While RESPs are typically used to save for a child's future education, there's nothing stopping an adult from opening an RESP for himself. If you've never had one, you can deposit $50,000 of after-tax money to grow on a tax-deferred basis for up to 36 years ... as far as I understand. An adult RESP will not qualify for CESG. Moreover, if you use the RESP strictly as a tax shelter and don't make qualified educational withdrawals when the time comes, your original contributions still come out free of tax but you'll pay ordinary income tax plus 20% additional tax on the earnings portion. That's the \\\"\\\"catch\\\"\\\"*. *However, if at that time you have accumulated sufficient RRSP contribution room, you may move up to $50,000 of your RESP earnings into your RRSP without any tax consequences (i.e. also avoiding the 20% additional tax) at time of transfer. Perhaps there's something above you haven't considered. Still, be sure to do your own due diligence and to consult a qualified, experienced, and conflict-free financial advisor for advice particular to your own situation.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"451301\",\n \"text\": \"\\\"From Wikipedia - Stock: The stock (also capital stock) of a corporation constitutes the equity stake of its owners. It represents the residual assets of the company that would be due to stockholders after discharge of all senior claims such as secured and unsecured debt. Stockholders' equity cannot be withdrawn from the company in a way that is intended to be detrimental to the company's creditors Wikipedia - Dividend: A dividend is a payment made by a corporation to its shareholders, usually as a distribution of profits. When a corporation earns a profit or surplus, it can re-invest it in the business (called retained earnings), and pay a fraction of this reinvestment as a dividend to shareholders. Distribution to shareholders can be in cash (usually a deposit into a bank account) or, if the corporation has a dividend reinvestment plan, the amount can be paid by the issue of further shares or share repurchase. Wikipedia - Bond: In finance, a bond is an instrument of indebtedness of the bond issuer to the holders. It is a debt security, under which the issuer owes the holders a debt and, depending on the terms of the bond, is obliged to pay them interest (the coupon) and/or to repay the principal at a later date, termed the maturity date. Interest is usually payable at fixed intervals (semiannual, annual, sometimes monthly). Very often the bond is negotiable, i.e. the ownership of the instrument can be transferred in the secondary market. This means that once the transfer agents at the bank medallion stamp the bond, it is highly liquid on the second market. Thus, stock is about ownership in the company, dividends are the payments those owners receive, which may be additional shares or cash usually, and bonds are about lending money. Stocks are usually bought through brokers on various stock exchanges generally. An exception can be made under \\\"\\\"Employee Stock Purchase Plans\\\"\\\" and other special cases where an employee may be given stock or options that allow the purchase of shares in the company through various plans. This would apply for Canada and the US where I have experience just as a parting note. This is without getting into Convertible Bond that also exists: In finance, a convertible bond or convertible note or convertible debt (or a convertible debenture if it has a maturity of greater than 10 years) is a type of bond that the holder can convert into a specified number of shares of common stock in the issuing company or cash of equal value. It is a hybrid security with debt- and equity-like features. It originated in the mid-19th century, and was used by early speculators such as Jacob Little and Daniel Drew to counter market cornering. Convertible bonds are most often issued by companies with a low credit rating and high growth potential.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"27671\",\n \"text\": \"\\\"For an RRSP, you do not have to pay taxes on money or investments until you withdraw the money. If you do not reinvest the dividends but instead, take them out as cash, that would be withdrawing the money. For mutual funds, you would normally reinvest the dividends if holding the investment inside an RRSP. For stocks, I believe the dividends would end up sitting in the cash part of your RRSP account (and you'd probably use the money to buy more stocks, though would not be required to do so). Either way, you do not pay tax on this investment income unless you withdraw it from your RRSP. For example, you invest $10,000 inside your RRSP. You get the tax benefit from doing so. You get dividends of $1,000 (hey, it was a good year), and use these to buy more stock. As the money never left your RRSP account, you are considered to have invested only your initial $10,000. If instead, you withdraw the $1,000 in dividends, you are taxed on $1000 income. TFSA are slightly more complicated. You don't get a tax benefit from your initial contribution, but then do not pay tax when you withdraw from the TFSA. Your investment income is still tax-free, and you are (generally) much more limited in how much you can contribute. For example, you invest $10,000 inside your TFSA. You get dividends of $1,000, and use these to buy more stock. Your total contributions to your TFSA remains at $10,000 as the money never left your account. You could instead withdraw the $1000 from your TFSA and would not pay tax on it. In the next calendar year (or later) after the withdrawal, you could \\\"\\\"repay\\\"\\\" the $1000 you took out without suffering an overcontribution penalty. This makes TFSA an excellent place to park emergency funds, as you can withdraw and subsequently replace the investment while continuing to get the tax benefits on your investment income. RRSPs are better for retirement or for the home buyers plan. In general, you should not be withdrawing money from either your TFSA or RRSP, except in emergencies, when retiring, or when purchasing a home. I prefer indexed mutual funds or money market accounts for both my RRSP and TFSA rather than individual stocks, but that's up to you.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"307832\",\n \"text\": \"I don't believe from reading the responses above that Questrade is doing anything 'original' or 'different' much less 'bad'. In RRSPs you are not allowed to go into debt. So the costs of all trades must be covered. If there is not enough USD to pay the bill then enough CAD is converted to do so. What else would anyone expect? How margin accounts work depends on whether the broker sets up different accounts for different currencies. Some do, some don't. The whole point of using 'margin' is to buy securities when you don't have the cash to cover the cost. The result is a 'short' position in the cash. Short positions accrue interest expense which is added to the balance once a month. Every broker does this. If you buy a US stock in a USD account without the cash to cover it, you will end up with USD margin debt. If you buy US stock in an account that co-mingles both USD and CAD assets and cash, then there will be options during the trade asking if you want to settle in USD or CAD. If you settle in CAD then obviously the broker will convert the necessary CAD funds to pay for it. If you settle in US funds, but there is no USD cash in the account, then again, you have created a short position in USD.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"312811\",\n \"text\": \"\\\"Share sales & purchases are accounted only on the balance sheet & cash flow statement although their effects are seen on the income statement. Remember, the balance sheet is like a snapshot in time of all accrued accounts; it's like looking at a glass of water and noting the level. The cash flow and income statements are like looking at the amount of water, \\\"\\\"actually\\\"\\\" and \\\"\\\"imaginary\\\"\\\" respectively, pumped in and out of the glass. So, when a corporation starts, it sells shares to whomever. The amount of cash received is accounted for in the investing section of the cash flow statement under the subheading \\\"\\\"issuance (retirement) of stock\\\"\\\" or the like, so when shares are sold, it is \\\"\\\"issuance\\\"\\\"; when a company buys back their shares, it's called \\\"\\\"retirement\\\"\\\", as cash inflows and outflows respectively. If you had a balance sheet before the shares were sold, you'd see under the \\\"\\\"equity\\\"\\\" heading a subheading common stock with a nominal (irrelevant) par value (this is usually something obnoxiously low like $0.01 per share used for ease of counting the shares from the Dollar amount in the account) under the subaccount almost always called \\\"\\\"common stock\\\"\\\". If you looked at the balance sheet after the sale, you'd see the number of shares in a note to the side. When shares trade publicly, the corporation usually has very little to do with it unless if they are selling or buying new shares under whatever label such as IPO, secondary offering, share repurchase, etc, but the corporation's volume from such activity would still be far below the activity of the third parties: shares are trading almost exclusively between third parties. These share sales and purchases will only be seen on the income statement under earnings per share (EPS), as EPS will rise and fall with stock repurchases and sales assuming income is held constant. While not technically part of the income statement but printed with it, the \\\"\\\"basic weighted average\\\"\\\" and \\\"\\\"diluted weighted average\\\"\\\" number of shares are also printed which are the weighted average over the reporting period of shares actually issued and expected if all promises to issue shares with employee stock options, grants, convertibles were made kept. The income statement is the accrual accounts of the operations of the company. It has little detail on investing (depreciation & appreciation) or financing (interest expenses & preferred dividends).\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"304085\",\n \"text\": \"Any time there is a share adjustment from spin-off, merger, stock split, or reverse slit; there is zero chance for the stockholders to hang on to fractional shares. They are turned into cash. For the employees in the 401K program or investors via a mutual fund or ETF this isn't a problem. Because the fraction of a share left over is compared to the thousands or millions of shares owned by the fund as a collective. For the individual investor in the company this can be a problem that they aren't happy about. In some cases the fractional share is a byproduct that will result from any of these events. In the case of a corporate merger or spin-off most investors will not have an integer number of shares, so that fraction leftover that gets converted to cash isn't a big deal. When they want to boost the price to a specific range to meet a regulatory requirement, they are getting desperate and don't care that some will be forced out. In other cases it is by design to force many shareholders out. They want to go private. They to 1-for-1000 split. If you had less than 1000 shares pre-split then you will end up with zero shares plus cash. They know exactly what number to use. The result after the split is that the number of investors is small enough they they can now fall under a different set of regulations. They have gone dark, they don't have to file as many reports, and they can keep control of the company. Once the Board of Directors or the majority stockholders votes on this, the small investors have no choice.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"433069\",\n \"text\": \"I personally spoke with a Questrade agent about my question. To make a long story short: in a margin account, you are automatically issued a loan when buying U.S. stock with a Canadian money. Whereas, in a registered account (e.g. RRSP), the amount is converted on your behalf to cover the debit balance. Me: What happens if I open an account and I place an order for U.S. stocks with Canadian money? Is the amount converted at the time of transfer? How does that work? Agent: In a margin account, you are automatically issued a loan for a currency you do not have, however, if you have enough buying power, it will go through. The interest on the overnight balance is calculated daily and is charged on a monthly basis. We do not convert funds automatically in a margin account because you can have a debit cash balance. Agent: In a registered account, the Canada Revenue Agency does not allow a debit balance and therefore, we must convert your funds on your behalf to cover the debit balance if possible. We convert automatically overnight for a registered account. Agent: For example, if you buy U.S. equity you will need USD to buy it, and if you only have CAD, we will loan you USD to cover for that transaction. For example, if you had only $100 CAD and then wanted to buy U.S. stock worth $100 USD, then we will loan you $100 USD to purchase the stock. In a margin account we will not convert the funds automatically. Therefore, you will remain to have a $100 CAD credit and a $100 USD debit balance (or a loan) in your account. Me: I see, it means the longer I keep the stock, the higher interest will be? Agent: Well, yes, however, in a registered account there will be not be any interest since we convert your funds, but in a margin account, there will be interest until the debit balance is covered, or you can manually convert your funds by contacting us.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"177648\",\n \"text\": \"Your first scenario, involving shareholders in a private corp being limited by a contractual agreement, is common in practice. Frequent clauses include methods of valuing the shares if someone wants to sell, first right of refusal [you have to attempt to sell to the other shareholders, before you can sell to a 3rd party], and many others. These clauses are governed by contract law [ie: some clauses may be illegal in contract law, and therefore couldn't be applied here]. A Universal Shareholders' Agreement is just the same as the above, but applied to more people. You would never get an already public company to convert to a universal shareholders' agreement - because even 1 share voting 'no' would block it [due to corporate law limiting the power of a corporation from abusing minority shareholder value]. In practice, these agreements universally exist at the start of incorporation, or at least at the first moment shares become available. An example is the Canadian mega-construction company PCL*, which is employee-owned. When the original owner transferred the corporation to his employees, there was a USA in place which still today governs how the corporation operates. In theory you could have a 'public company' where most shares are already owned by the founders, and 100% of remaining shares are owned by a specific group of individuals, in which case you may be able to get a USA signed. But it wouldn't really happen in practice. *[Note that while PCL is broadly owned by a large group of employees, it is not a 'public company' because any random schmuck can't simply buy a share on the Toronto Stock Exchange. I assume most exchanges would prevent corporations from being listed if they had ownership restrictions like this].\",\n \"title\": \"\"\n },\n {\n \"docid\": \"213767\",\n \"text\": \"\\\"The first 3 are the same as owning stock in a company would be measured in shares and would constitute some percentage of the overall shares outstanding. If there are 100 shares in the company in total, then owning 80 shares is owning 80% is the same as owning 80% of the common stock. This would be the typical ownership case though there can also be \\\"\\\"Restricted stock\\\"\\\" as something to note here. Convertible debt would likely carry interest charges as well as the choice at the end of becoming stock in the company. In this case, until the conversion is done, the stock isn't issued and thus isn't counted. Taking the above example, one could have a note that could be worth 10 shares but until the conversion is done, the debt is still debt. Some convertible debt could carry options or warrants for the underlying stock as there was the Berkshire convertible notes years ago that carried a negative interest rate that was studied in \\\"\\\"The Negative Coupon Bond\\\"\\\" if you want an example here. Options would have the right but not the obligation to buy the stock where there are \\\"\\\"Incentive Stock Options\\\"\\\" to research this in more depth. In this case, one could choose to not exercise the option and thus no stock changes hands. This is where some companies will experience dilution of ownership as employees and management may be given options that put more shares out to the public. Issuing debt wouldn't change the ownership and isn't direct ownership unless the company goes through a restructuring where the creditors become the new stock holders in the case of a Chapter 11 situation in the US. Note that this isn't really investing in a small business as much as it is making a loan to the company that will be paid back in cash. If the company runs into problems then the creditor could try to pursue the assets of the company to be repaid.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"19433\",\n \"text\": \"I believe your question is based on a false premise. First, no broker, that I know of, provides an RRSP account that is a margin account. RRSP accounts follow cash settlement rules. If you don't have the cash available, you can't buy a stock. You can't borrow money from your broker within your RRSP. If you want to borrow money to invest in your RRSP, you must borrow outside from another source, and make a contribution to your RRSP. And, if you do this, the loan interest is not considered tax deductible. In order for investment loan interest to be tax deductible, you'd need to invest outside of a registered type of account, e.g. using a regular non-tax-sheltered account. Even then, what you can deduct may be limited. Refer to CRA - Line 221 - Carrying charges and interest expenses: You can claim the following carrying charges and interest [...] [...] You cannot deduct on line 221 any of the following amounts:\",\n \"title\": \"\"\n },\n {\n \"docid\": \"161201\",\n \"text\": \"Your assumption that funds sold in GBP trade in GBP is incorrect. In general funds purchase their constituent stocks in the fund currency which may be different to the subscription currency. Where the subscription currency is different from the fund currency subscriptions are converted into the fund currency before the extra money is used to increase holdings. An ETF, on the other hand, does not take subscriptions directly but by creation (and redemption) of shares. The principle is the same however; monies received from creation of ETF shares are converted into the fund currency and then used to buy stock. This ensures that only one currency transaction is done. In your specific example the fund currency will be USD so your purchase of the shares (assuming there are no sellers and creation occurs) will be converted from GBP to USD and held in that currency in the fund. The fund then trades entirely in USD to avoid currency risk. When you want to sell your exposure (supposing redemption occurs) enough holdings required to redeem your money are sold to get cash in USD and then converted to GBP before paying you. This means that trading activity where there is no need to convert to GBP (or any other currency) does not incur currency conversion costs. In practice funds will always have some cash (or cash equivalents) on hand to pay out redemptions and will have an idea of the number and size of redemptions each calendar period so will use futures and swaps to mitigate FX risk. Where the same firm has two funds traded in different currencies with the same objectives it is likely that one is a wrapper for the other such that one simply converts the currency and buys the other currency denominated ETF. As these are exchange traded funds with a price in GBP the amount you pay for the ETF or gain on selling it is the price given and you will not have to consider currency exchange as that should be done internally as explained above. However, there can be a (temporary) arbitrage opportunity if the price in GBP does not reflect the price in USD and the exchange rate put together.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"589127\",\n \"text\": \"\\\"There are more than a few different ways to consider why someone may have a transaction in the stock market: Employee stock options - If part of my compensation comes from having options that vest over time, I may well sell shares at various points because I don't want so much of my new worth tied up in one company stock. Thus, some transactions may happen from people cashing out stock options. Shorting stocks - This is where one would sell borrowed stock that then gets replaced later. Thus, one could reverse the traditional buy and sell order in which case the buy is done to close the position rather than open one. Convertible debt - Some companies may have debt that come with warrants or options that allow the holder to acquire shares at a specific price. This would be similar to 1 in some ways though the holder may be a mutual fund or company in some cases. There is also some people that may seek high-yield stocks and want an income stream from the stock while others may just want capital appreciation and like stocks that may not pay dividends(Berkshire Hathaway being the classic example here). Others may be traders believing the stock will move one way or another in the short-term and want to profit from that. So, thus the stock market isn't necessarily as simple as you state initially. A terrorist attack may impact stocks in a couple ways to consider: Liquidity - In the case of the attacks of 9/11, the stock market was closed for a number of days which meant people couldn't trade to convert shares to cash or cash to shares. Thus, some people may pull out of the market out of fear of their money being \\\"\\\"locked up\\\"\\\" when they need to access it. If someone is retired and expects to get $x/quarter from their stocks and it appears that that may be in jeopardy, it could cause one to shift their asset allocation. Future profits - Some companies may have costs to rebuild offices and other losses that could put a temporary dent in profits. If there is a company that makes widgets and the factory is attacked, the company may have to stop making widgets for a while which would impact earnings, no? There can also be the perception that an attack is \\\"\\\"just the beginning\\\"\\\" and one could extrapolate out more attacks that may affect broader areas. Sometimes what recently happens with the stock market is expected to continue that can be dangerous as some people may believe the market has to continue like the recent past as that is how they think the future will be.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"525390\",\n \"text\": \"\\\"A company has 100,000 shares and 100,000 unexercised call options (company issued). Share price and strike price both at $1. What country is this related to? I ask because, in the US, most people I know associate a \\\"\\\"call\\\"\\\" option with the instrument that is equivalent to 100 shares. So 100,000 calls would be 10,000,000 shares, which exceeds the number of shares you're saying the company has. I don't know if that means you pulled the numbers out of thin air, or whether it means you're thinking of a different type of option? Perhaps you meant incentive stock options meant to be given to employees? Each one of those is equivalent to a single share. They just aren't called \\\"\\\"call options\\\"\\\". In the rest of my answer, I'm going to assume you meant stock options. I assume the fact that these options exist will slow any price increases on the underlying shares due to potential dilution? I don't think the company can just create stock options without creating the underlying shares in the first place. Said another way, a more likely scenario is that company creates 200,000 shares and agrees to float 50% of them while reserving the other 50% as the pool for incentive employee stock. They then choose to give the employees options on the stock in the incentive pool, rather than outright grants of the stock, for various reasons. (One of which is being nice to the employees in regards to taxes since there is no US tax due at grant time if the strike price is the current price of the underlying stock.) An alternative scenario when the company shares are liquidly traded is that the company simply plans to buy back shares from the market in order to give employees their shares when options are exercised. In this case, the company needs the cash on hand, or cash flow to take money from, to buy those shares at current prices. Anyway, in either case, there is no dilution happening WHEN the options get exercised. Any dilution happened before or at the time the options were created. Meaning, the total number of shares in the company was already pre-set at an earlier time. As a result, the fact that the options exist in themselves will not slow price changes on the stock. However, price changes will be impacted by the total float of shares in the company, or the impact to cash flow if the company has to buy shares to redeem its option commitments. This is almost the same thing you're asking about, but it is technically different as to timing. If this is the case, can this be factored into any option pricing models like black-scholes? You're including the effect just by considering the total float of shares and net profits from cash flow when doing your modelling.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"76530\",\n \"text\": \"\\\"All transactions within an IRA are irrelevant as far as the taxation of the distributions from the IRA are concerned. You can only take cash from an IRA, and a (cash) distribution from a Traditional IRA is taxable as ordinary income (same as interest from a bank, say) without the advantage of any of the special tax rates for long-term capital gains or qualified dividends even if that cash was generated within the IRA from sales of stock etc. In short, just as with what is alleged to occur with respect to Las Vegas, what happens within the IRA stays within the IRA. Note: some IRA custodians are willing to make a distribution of stock or mutual fund shares to you, so that ownership of the 100 shares of GE, say, that you hold within your IRA is transferred to you in your personal (non-IRA) brokerage account. But, as far as the IRS is concerned, your IRA custodian sold the stock as the closing price on the day of the distribution, gave you the cash, and you promptly bought the 100 shares (at the closing price) in your personal brokerage account with the cash that you received from the IRA. It is just that your custodian saved the transaction fees involved in selling 100 shares of GE stock inside the IRA and you saved the transaction fee for buying 100 shares of GE stock in your personal brokerage account. Your basis in the 100 shares of GE stock is the \\\"\\\"cash_ that you imputedly received as a distribution from the IRA, so that when you sell the shares at some future time, your capital gains (or losses) will be with respect to this basis. The capital gains that occurred within the IRA when the shares were imputedly sold by your IRA custodian remain within the IRA, and you don't get to pay taxes on that at capital gains rates. That being said, I would like to add to what NathanL told you in his answer. Your mother passed away in 2011 and you are now 60 years old (so 54 or 55 in 2011?). It is likely that your mother was over 70.5 years old when she passed away, and so she likely had started taking Required Minimum Distributions from her IRA before her death. So, You should have been taking RMDs from the Inherited IRA starting with Year 2012. (The RMD for 2011, if not taken already by your mother before she passed away, should have been taken by her estate, and distributed to her heirs in accordance with her will, or, if she died intestate, in accordance with state law and/or probate court directives). There would not have been any 10% penalty tax due on the RMDs taken by you on the grounds that you were not 59.5 years old as yet; that rule applies to owners (your mom in this case) and not to beneficiaries (you in this case). So, have you taken the RMDs for 2012-2016? Or were you waiting to turn 59.5 before taking distributions in the mistaken belief that you would have to pay a 10% penalty for early wthdrawal? The penalty for not taking a RMD is 50% of the amount not distributed; yes, 50%. If you didn't take RMDs from the Inherited IRA for years 2012-2016, I recommend that you consult a CPA with expertise in tax law. Ask the CPA if he/she is an Enrolled Agent with the IRS: Enrolled Agents have to pass an exam administered by the IRS to show that they really understand tax law and are not just blowing smoke, and can represent you in front of the IRS in cases of audit etc,\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"212783\",\n \"text\": \"\\\"Federal taxes are generally lower in Canada. Canada's top federal income tax rate is 29%; the US rate is 35% and will go to 39.6% when Bush tax cuts expire. The healthcare surcharge will kick in in a few years, pushing the top bracket by a few more points and over 40%. State/provincial taxes are lower in the US. You may end up in the 12% bracket in New York City or around 10% in California or other \\\"\\\"bad\\\"\\\" income-tax states. But Alberta is considered a tax haven in Canada and has a 10% flat tax. Ontario's top rate is about 11%, but there are surtaxes that can push the effective rate to about 17%. Investment income taxes: Canada wins, narrowly. Income from capital gains counts as half, so if you're very rich and live in Ontario, your rate is about 23% and less than that in Alberta. The only way to match or beat this deal in the US in the long term is to live in a no-income-tax state. Dividends are taxed at rates somewhere between capital gains and ordinary income - not as good a deal as Bush's 15% rate on preferred dividends, but that 15% rate will probably expire soon. Sales taxes: US wins, but the gap is closing. Canada has a national VAT-like tax, called GST and its rate came down from 7% to 5% when Harper became the Prime Minister. Provinces have sales taxes on top of that, in the range of 7-8% (but Alberta has no sales tax). Some provinces \\\"\\\"harmonized\\\"\\\" their sales taxes with the GST and charge a single rate, e.g. Ontario has a harmonized sales tax (HST) of 13% (5+8). 13% is of course a worse rate than the 6-8% charged by most states, but then some states and counties already charge 10% and the rates have been going up in each recession. Payroll taxes: much lower in Canada. Canadian employees' CPP and EI deductions have a low threshold and top out at about $3,000. Americans' 7.65% FICA rate applies to even $100K, resulting in a tax of $7,650. Property taxes: too dependent on the location, hard to tell. Tax benefits for retirement savings: Canada. If you work in the US and don't have a 401(k), you get a really bad deal: your retirement is underfunded and you're stuck with a higher tax bill, because you can't get the deduction. In Canada, if you don't have an RRSP at work, you take the money to the financial company of your choice, invest it there, and take the deduction on your taxes. If you don't like the investment options in your 401(k), you're stuck with them. If you don't like them in your RRSP, contribute the minimum to get the match and put the rest of the money into your individual RRSP; you still get the same deduction. Annual 401(k) contribution limits are use-it-or-lose-it, while unused RRSP limits and deductions can be carried forward and used when you need to jump tax brackets. Canada used to lack an answer to Roth IRAs, but the introduction of TFSAs took care of that. Mortgage interest deduction: US wins here as mortgage interest is not deductible in Canada. Marriage penalty: US wins. Canadian tax returns are of single or married-filing-separately type. So if you have one working spouse in the family or a big disparity between spouses' incomes, you can save money by filing a joint return. But such option is not available in Canada (there are ways to transfer some income between spouses and fund spousal retirement accounts, but if the income disparity is big, that won't be enough). Higher education: cheaper in Canada. This is not a tax item, but it's a big expense for many families and something the government can do about with your tax dollars. To sum it up, you may face higher or lower or about the same taxes after moving from US to Canada, depending on your circumstances. Another message here is that the high-tax, socialist, investment-unfriendly Canada is mostly a convenient myth.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"442741\",\n \"text\": \"You don't seem to have any particular question to be answered. Your understanding of RRSPs seems to be very good. Have you considered whether you might be better off putting your retirement savings into a TFSA instead? Both types can protect your growth from taxation (provided you reinvest the refund from the RRSP). The main way in which the RRSP is better than TFSA is that you can pay the tax on the contribution at a time when your income is lower, and thus have a lower marginal tax rate. Most people retire with a lower income than during their earning years, but it's a matter of tax brackets. If you think you'll be in the same bracket (same marginal tax rate) when you retire, then the TFSA and RRSP work out even in that regard. So in your case, the question you want to ask yourself is: when I retire, will I have an income (including CPP, OAS, pension payments, etc) that exceeds $45,282 worth of today's dollars? If so, your RRSP holds no advantage over the TFSA. In fact, the RRSP may even be worse, since the withdrawals count as income and reduce the amount of OAS and perhaps GIS payments that the government gives you - at least under current regulations. If you're unsure, I suggest you try this calculator from taxtips.ca that runs both scenarios and helps you see which one is more beneficial. It even factors in the OAS/GIS clawbacks.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"12899\",\n \"text\": \"Full disclosure: I’m an intern for EquityZen, so I’m familiar with this space but can speak with the most accuracy about EquityZen. Observations about other players in the space are my own. The employee liquidity landscape is evolving. EquityZen and Equidate help shareholders (employees, ex-employees, etc.) in private companies get liquidity for shares they already own. ESOFund and 137 Ventures help with option financing, and provide loans (and exotic structures on loans) to cover costs of exercising options and any associated tax hit. EquityZen is a private company marketplace that led the second wave of VC-backed secondary markets starting early 2013. The mission is to help achieve liquidity for employees and other private company shareholder, but in a company-approved way. EquityZen transacts with share transfers and also a proprietary derivative structure which transfers economics of a company's shares without changing voting and information rights. This structure typically makes the transfer process cheaper and faster as less paperwork is involved. Accredited investors find the process appealing because they get access to companies they usually cannot with small check sizes. To address the questions in Dzt's post: 1). EquityZen doesn't take a 'loan shark' approach meaning they don't front shareholders money so that they can purchase their stock. With EquityZen, you’re either selling your shares or selling all the economic risk—upside and downside—in exchange for today’s value. 2). EquityZen only allows company approved deals on the platform. As a result, companies are more friendly towards the process and they tend to allow these deals to take place. Non-company approved deals pose risks for buyers and sellers and are ultimately unsustainable. As a buyer, without company blessing, you’re taking on significant counterparty risk from the seller (will they make good on their promise to deliver shares in the future?) or the risk that the transfer is impermissible under relevant restrictions and your purchase is invalid. As a seller, you’re running the risk of violating your equity agreements, which can have severe penalties, like forfeiture of your stock. Your shares are also much less marketable when you’re looking to transact without the company’s knowledge or approval. 3). Terms don't change depending an a shareholder's situation. EquityZen is a professional company and values all of the shareholders that use the platform. It’s a marketplace so the market sets the price. In other situations, you may be at the mercy of just one large buyer. This can happen when you’re facing a big tax bill on exercise but don’t have the cash (because you have the stock). 4). EquityZen doesn't offer loans so this is a non issue. 5). Not EquityZen! EquityZen creates a clean break from the economics. It’s not uncommon for the loan structures to use an interest component as well as some other complications, like upside participation and and also a liquidation preference. EquityZen strives for a simple structure where you’re not on the hook for the downside and you’ve transferred all the upside as well.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"331268\",\n \"text\": \"The term self-directed generally refers to RRSP accounts where the account holder has not only the ability to determine a basic investment asset mix (such as can be accomplished even with a limited selection of mutual funds) but, more specifically, the self-directed account holder has a much wider choice of financial instruments beyond mutual funds, GICs, and/or cash savings. A self-directed RRSP generally permits the account holder to also invest or trade directly in financial instruments such as: Those kinds of instruments are not typically available in a non-self-directed mutual fund or bank RRSP. Typical mutual fund or bank RRSPs offer you only their choice of products – often with higher fees attached. Related resources:\",\n \"title\": \"\"\n },\n {\n \"docid\": \"17208\",\n \"text\": \"See my comment for some discussion of why one might choose an identical fund over an ETF. As to why someone would choose the higher cost fund in this instance ... The Admiral Shares version of the fund (VFIAX) has the same expense ratio as the ETF but has a minimum investment of $10K. Some investors may want to eventually own the Admiral Shares fund but do not yet have $10K. If they begin with the Investor Shares now and then convert to Admiral later, that conversion will be a non-taxable event. If, however, they start with ETF shares now and then sell them later to buy the fund, that sale will be a taxable event. Vanguard ETFs are only commission-free to Vanguard clients using Vanguard Brokerage Services. Some investors using other brokers may face all sorts of penalties for purchasing third-party ETFs. Some retirement plan participants (either at Vanguard or another broker) may not even be allowed to purchase ETFs.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"103842\",\n \"text\": \"Does the 5 year rule apply on the After-tax 401k -> Roth 401k -> Roth IRA conversion of the 20000 (including 10000 earnings that was originally pre-tax)? No. The after-tax amounts are not subject to the 5 years rule. The earnings are. How does this affect Roth IRA withdrawal ordering rules with respect to the taxable portion of a single conversion being withdrawn before the non-taxable portion? Taxable portion first until exhausted. To better understand how it works, you need to understand the rationale behind the 5-year rule. Consider you have $100K in your IRA (traditional) and you want to take it out. Just withdrawing it would trigger a 10K statutory penalty, on top of the taxes due. But, you can use the backdoor Roth IRA, right? So convert the 100K, and then it becomes after-tax contribution to Roth IRA, and can be withdrawn with no penalty. One form filled ad 10K saved. To block this loophole, here comes the 5 years rule: you cannot withdraw after-tax amounts for at least 5 years without penalty, if the source was taxable conversion. Thus, in order to avoid the 10K penalty in the above situation, you have a 5-year cooling period, which makes the loophole useless for most cases. However amounts that are after tax can be withdrawn without penalty already, even from the traditional IRA, so there's no need in the 5 years cooling period. The withdrawal attribution is in this order: Roth IRA rollovers are sourced to the origin. E.g.: if you converted $100 to the Roth IRA at firm X and then a year later rolled it over to firm Y - it doesn't affect anything and the clock is ticking from the original date of the conversion at firm X. 5-year period applies to each conversion/rollover from a qualified retirement plan (see here). Distributions are applied to the conversions in FIFO order, so in one distribution, depending on the amounts, you may hit several different incoming conversions. The 5 years should be check on each of them, and the penalty applied on the amounts attributable to those that don't have enough time. 5-year period for contributions applies starting from the beginning of the first year of the first contribution that established your Roth IRA plan. The penalty applies to the amounts that were included in your gross income when conversion occurred, i.e.: doesn't apply on the amounts converted from after-tax sources. Note the difference from the traditional IRA - distributions from pre-tax sources are prorated between the non-deductible (basis) amounts and the deductible/earnings amounts (taxable). That is why the taxable amounts are first in the ordering of the distributions.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"481169\",\n \"text\": \"Firstly a stock split is easy, for example each unit of stock is converted into 10 units. So if you owned 1% of the company before the stock split, you will still own 1% after the stock split, but have 10 times the number of shares. The company does not pay out any money when doing this and there is no effect on tax for the company or the share holder. Now onto stock dividend… When a company make a profit, the company gives some of the profit to the share holders as a dividend; this is normally paid in cash. An investor may then wish to buy more shares in the company using the money from the dividend. However buying shares used to have a large cost in broker charges etc. Therefore some companies allowed share holders to choose to have the dividend paid as shares. The company buys enough of their own shares to cover the payout, only having one set of broker charges and then sends the correct number of shares to each share holder that has opted for a stock dividend. (Along with any cash that was not enough to buy a complete share.) This made since when you had paper shares and admin costs where high for stock brokers. It does not make sense these days. A stock dividend is taxed as if you had been paid the dividend in cash and then brought the stock yourself.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"88539\",\n \"text\": \"There are two significant drawbacks to this type of transfer. They were the reasons why I kept my American 401(k) as-is and started funding my Canadian RRSP from zero balance. 1. Taxes - a large chunk of your 401(k) will be lost to taxes. There is probably no way to transfer the funds without making a 401(k)/IRA withdrawal, which will incur the US federal tax and the 10% early-withdrawal penalty. When the money went into the 401(k), you got a tax deduction in the US and the tax break is supposed be repaid later when you make a withdrawal (that's basically how tax deferral works). It's unlikely that any country will let you take a deduction first and send the payback to a foreign country. The withdrawal amount may also be taxable in Canada (Canadians generally pay taxes on their global income and that includes pensions and distributions from foreign retirement plans). Foreign tax credit will apply of course, to eliminate double taxation, but it's of little help if your marginal Canadian tax rate is higher than your average US tax rate. 2. Expenses. Your RRSP will have to be invested in something and mutual fund management expenses are generally higher in Canada than in the US. For example, my employer-sponsored RRSP has a Standard & Poor's stock index fund that charges 1.5% and that is considered low-cost. It also offers a number of managed funds with expenses in excess of 2% that I simply ignore. You can probably invest your American 401(k)/IRA in mutual funds more efficiently.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"394734\",\n \"text\": \"Employees were already cashing out their RSUs and selling stock on private markets. >Even if Facebook could resist, an eager army of Facebook employees is pushing hard for an I.P.O., according to Eric Eldon of TechCrunch. In 2008, Facebook adopted a new restricted stock program that prevented employees from selling their shares until an I.P.O. or a sale, or if Facebook permitted it. They still could have stayed private if they really wanted to. They were compensating employees in stock, and those employees wanted to cash out. The underwriters wanted to cash out before the financials became open to public scrutiny.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"152049\",\n \"text\": \"\\\"I have some money invested on Merrill Edge. 2 days ago I purchased some mutual funds with most of the rest of my money in my account. I logged in today to see how it did, and noticed that there are 3 sections: Priced Investments, Cash & Money Accounts, and Pending Activity. In the Cash & Money section, there shows a negative balance of Cash (let's say -$1,000) and a positive \\\"\\\"Money Account Value\\\"\\\" (let's say +$1,100). The \\\"\\\"Money Account\\\"\\\" appears to be made up of $1 shares of something called \\\"\\\"ML Direct Deposit Program\\\"\\\". However, even though the mutual fund purchase was made 2 days ago, and the shares of the mutual funds are officially in my account, I'm still showing all of my \\\"\\\"Money Account\\\"\\\" shares ($1000). The balance sheet effectively makes it look like I somehow needed to have \\\"\\\"sold\\\"\\\" back my money account shares, converted them to cash, and then bought the funds. I'm hoping that isn't the case, and for some reason, there is a multiday lag between me buying stock and money getting deducted from my \\\"\\\"Money Account\\\"\\\". Hope that all makes sense. TLDR: what's the diff between a Cash account and Money Account that's filled with shares of \\\"\\\" ML Direct Deposit Program\\\"\\\"? Edit: Today the cash and money account offset by equal values equal to one of my mutual fund purchases.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"312679\",\n \"text\": \"Here's the best explanation I found relating to why your T4 box 39 might not have an amount filled in, even when box 38 has one: Department of Finance – Explanatory Notes Relating to the Income Tax Act [...]. It's a long document, but here's the part I believe relevant, with my emphasis: Employee Stock Options ITA 110(1) [...] Paragraph 110(1)(d) is amended to include a requirement that the employee [...] exercise the employee’s rights under the stock option agreement and acquire the securities underlying the agreement in order for the deduction in computing taxable income to be available [...] ensures that only one deduction is available in respect of an employment benefit. In other words, if employee stock option rights are surrendered to an employer for cash or an in-kind payment, then (subject to new subsections 110(1.1) and (1.2)) the employer may deduct the payment but the employee cannot claim the stock option deduction. Conversely, where an employer issues securities pursuant to an employee’s exercise of stock options, the employer can not deduct an amount in respect of the issuance, but the employee may be eligible to claim a deduction under paragraph 110(1)(d). Did you receive real shares based on your participation in the ESPP, or did you get a cash payment for the net value of shares you would have been issued under the plan? From what I can tell, if you opted for a cash payment (or if your plan only allows for such), then the part I emphasized comes into play. Essentially, if conditions were such that your employer could claim a deduction on their corporate income tax return for the compensation paid to you as part of the plan, then you are not also able to claim a similar deduction on your personal income tax return. The money received in that manner is effectively taxed in your hands the same as any bonus employment income would be; i.e. it isn't afforded tax treatment equivalent to capital gains income. Your employer and/or ESPP administrator are best able to confirm the conditions which led to no amount in your box 39, but at least based on above you can see there are legitimate cases where box 38 would have an amount while box 39 doesn't.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"127958\",\n \"text\": \"I think you are having trouble understanding what 'liquid' means. Liquidity refers to how easily an asset can be converted to cash. More liquid = more easily converted to cash, less liquid, less so. Any kind of exit load is going to make an asset less liquid due to the penalties associated with making the sale. So, the whole point of liquid funds is to give people the option of selling quickly if they need to. Since an exit load is meant to discourage this behavior, liquid funds tend not to have one. The point isn't what the financial institution 'gets', it's about offering a service to clients with a particular investment need.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"444568\",\n \"text\": \"There are some great answers on this site similar to what you asked, with either a non-jurisdictional or a US-centric focus. I would read those answers as well to give yourself more points of view on early investing. There are a few differences between Canada and the US from an investing perspective that you should also then consider, namely tax rules, healthcare, and education. I'll get Healthcare and Education out of the way quickly. Just note the difference in perspective in Canada of having government healthcare; putting money into health-savings plans or focusing on insurance as a workplace benefit is not a key motivating factor, but more a 'nice-to-have'. For education, it is more common in Canada for a student to either pay for school while working summer / part-time jobs, or at least taking on manageable levels of debt [because it is typically not quite as expensive as private colleges in the US]. There is still somewhat of a culture of saving for your child's education here, but it is not as much of a necessity as it may be in the US. From an investing perspective, I will quickly note some common [though not universal] general advice, before getting Canadian specific. I have blatantly stolen the meat of this section from Ben Miller's great answer here: Oversimplify it for me: the correct order of investing Once you have a solid financial footing, some peculiarities of Canadian investing are below. For all the tax-specific plans I'm about to mention, note that the banks do a very good job here of tricking you into believing they are complex, and that you need your hand to be held. I have gotten some criminally bad tax advice from banking reps, so at the risk of sounding prejudiced, I recommend that you learn everything you can beforehand, and only go into your bank when you already know the right answer. The 'account types' themselves just involve a few pages of paperwork to open, and the banks will often do that for free. They make up their fees in offering investment types that earn them management fees once the accounts are created. Be sure to separate the investments (stocks vs bonds etc.) vs the investment vehicles. Canada has 'Tax Free Savings Accounts', where you can contribute a certain amount of money every year, and invest in just about anything you want, from bonds to stocks to mutual funds. Any Income you earn in this account is completely tax free. You can withdraw these investments any time you want, but you can't re-contribute until January 1st of next year. ie: you invest $5k today in stocks held in a TFSA, and they grow to $6k. You withdraw $6k in July. No tax is involved. On January 1st next year, you can re-contribute a new $6K, and also any additional amounts added to your total limit annually. TFSA's are good for short-term liquid investments. If you don't know for sure when you'll need the money, putting it in a TFSA saves you some tax, but doesn't commit you to any specific plan of action. Registered Retirement Savings Plans allow you to contribute money based on your employment income accrued over your lifetime in Canada. The contributions are deducted from your taxable income in the year you make them. When you withdraw money from your RRSP, the amount you withdraw gets added as additional income in that year. ie: you invest $5k today in stocks held in an RRSP, and get a $5k deduction from your taxable income this year. The investments grow to $6k. You withdraw $6k next year. Your taxable income increases by $6k [note that if the investments were held 'normally' {outside of an RRSP}, you would have a taxable gain of only 50% of the total gain; but withdrawing the amount from your RRSP makes the gain 100% taxable]. On January 1st next year, you CANNOT recontribute this amount. Once withdrawn, it cannot be recontributed [except for below items]. RRSP's are good for long-term investing for retirement. There are a few factors at play here: (1) you get an immediate tax deduction, thus increasing the original size of investment by deferring tax to the withdrawal date; (2) your investments compound tax-free [you only pay tax at the end when you withdraw, not annually on earnings]; and (3) many people expect that they will have a lower tax-rate when they retire, than they do today. Some warnings about RRSP's: (1) They are less liquid than TFSA's; you can't put money in, take it out, and put it in again. In general, when you take it out, it's out, and therefore useless unless you leave it in for a long time; (2) Income gets re-characterized to be fully taxable [no dividend tax credits, no reduced capital gains tax rate]; and (3) There is no guarantee that your tax rate on retirement will be less than today. If you contribute only when your tax rate is in the top bracket, then this is a good bet, but even still, in 30 years, tax rates might rise by 20% [who knows?], meaning you could end up paying more tax on the back-end, than you saved in the short term. Home Buyer Plan RRSP withdrawals My single favourite piece of advice for young Canadians is this: if you contribute to an RRSP at least 3 months before you make a down payment on your first house, you can withdraw up to $25k from your RRSP without paying tax! to use for the down payment. Then over the next ~10 years, you need to recontribute money back to your RRSP, and you will ultimately be taxed when you finally take the money out at retirement. This means that contributing up to 25k to an RRSP can multiply your savings available for a down payment, by the amount of your tax rate. So if you make ~60k, you'll save ~35% on your 25k deposited, turning your down payment into $33,750. Getting immediate access to the tax savings while also having access to the cash for a downpayment, makes the Home Buyer Plan a solid way to make the most out of your RRSP, as long as one of your near-term goals is to own your own home. Registered Pension Plans are even less liquid than RRSPs. Tax-wise, they basically work the same: you get a deduction in the year you contribute, and are taxed when you withdraw. The big difference is that there are rules on when you are allowed to withdraw: only in retirement [barring specific circumstances]. Typically your employer's matching program (if you have one) will be inside of an RPP. Note that RPP's and RRSP's reduce your taxes on your employment paycheques immediately, if you contribute through a work program. That means you get the tax savings during the year, instead of all at once a year later on April 30th. *Note that I have attempted at all times to keep my advice current with applicable tax legislation, but I do not guarantee accuracy. Research these things yourself because I may have missed something relevant to your situation, I may be just plain wrong, and tax law may have changed since I wrote this to when you read it.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"399932\",\n \"text\": \"As a rule of thumb, no. Only in very rare circumstances will it prove better than a RRSP. The media has overplayed the usefulness of this account type for retirement savings. That's just a general rule. Your specific situation will make a difference but it's very easy to show that RRSPs will always outperform if the marginal rates are lower on withdrawal than when you deduct contributions from income. If you plan to use the money before retirement or you're expecting to collect GIS on retirement then you may need to look at the specifics of your situation. If you plan to put money in a RRSP and carry forward the deduction to use at a later date then it doesn't matter whether you put it in a RRSP now or use the TFSA and transfer it later. The RRSP also has advantages of some tax treaties and creditor protection. It (as a RRIF) can also be used after 65 for income splitting and the pension credit. An RESP can also provide a greater return as you get free money, which is always good. There are many other things you can do with it but I'd say it's always better in a TFSA than paying tax in a regular account. Since you pay the mortgage with after tax dollars that could be another option for the cash and it's a guaranteed return, albeit small nowadays.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"68609\",\n \"text\": \"\\\"I was told if I moved my 401k into a Roth IRA that school purposes is one reasons you can withdraw money without having to pay a tax. Incorrect. You will need to pay tax on the amount converted, since a 401(k) is pre-tax and a Roth IRA is after-tax. It will be added to your regular income, so you will pay tax at your marginal tax rate. is there any hidden tax or fee at all for withdrawing money from a Roth IRA for educational purposes? You still will need to pay the tax on the amount converted, but you'll avoid the 10% penalty for early withdrawal. I know that tuition, books and fees are covered for educational purposes. Can I take out of my Roth IRA for living expenses while I'm attending school? Rent, gas, food, etc... Room and board, yes, so long as you are half-time, but not gas/food Possibly only room and board for staying on-campus, but I'm not certain, although I doubt you could call your normal house payment \\\"\\\"education expense\\\"\\\" with my 401k being smaller, would it just be better to go ahead and cash the whole thing and just pay the tax and use it for whatever I need it for? What is the tax if I just decide to cash the whole thing in? You pay your marginal tax rate PLUS a 10% penalty for early withdrawal. So no, this is probably not a wise move financially unless you're on the verge of bankruptcy or foreclosure (where distress costs are much higher then the 10% penalty) I can't answer the other questions regarding grants; I would talk to the financial aid department at your school. Bottom line, transferring your 401(k) is very likely a bad idea unless you can afford to pay the tax in cash (meaning without borrowing). My advice would be to leave your 401(k) alone (it's meant for retirement not for school or living expenses) Ideally, you should pay for as much as you can out of cash flow, and don't take out more student loans. That may mean taking fewer classes, getting another part time job, finding a different (cheaper) school, applying for more grants and scholarships, etc. I would not in ANY circumstance cash out your 401(k) to pay for school. You'll be much worse off in the long run, and there are much cheaper ways to get money.\\\"\",\n \"title\": \"\"\n }\n]"}}},{"rowIdx":197,"cells":{"query_id":{"kind":"string","value":"687"},"query":{"kind":"string","value":"Lamins are found within the inner layer of the nuclear membrane of all cells."},"positive_passages":{"kind":"list like","value":[{"docid":"4452659","text":"Macroautophagy (hereafter referred to as autophagy) is a catabolic membrane trafficking process that degrades a variety of cellular constituents and is associated with human diseases. Although extensive studies have focused on autophagic turnover of cytoplasmic materials, little is known about the role of autophagy in degrading nuclear components. Here we report that the autophagy machinery mediates degradation of nuclear lamina components in mammals. The autophagy protein LC3/Atg8, which is involved in autophagy membrane trafficking and substrate delivery, is present in the nucleus and directly interacts with the nuclear lamina protein lamin B1, and binds to lamin-associated domains on chromatin. This LC3-lamin B1 interaction does not downregulate lamin B1 during starvation, but mediates its degradation upon oncogenic insults, such as by activated RAS. Lamin B1 degradation is achieved by nucleus-to-cytoplasm transport that delivers lamin B1 to the lysosome. Inhibiting autophagy or the LC3-lamin B1 interaction prevents activated RAS-induced lamin B1 loss and attenuates oncogene-induced senescence in primary human cells. Our study suggests that this new function of autophagy acts as a guarding mechanism protecting cells from tumorigenesis.","title":"Autophagy mediates degradation of nuclear lamina"}],"string":"[\n {\n \"docid\": \"4452659\",\n \"text\": \"Macroautophagy (hereafter referred to as autophagy) is a catabolic membrane trafficking process that degrades a variety of cellular constituents and is associated with human diseases. Although extensive studies have focused on autophagic turnover of cytoplasmic materials, little is known about the role of autophagy in degrading nuclear components. Here we report that the autophagy machinery mediates degradation of nuclear lamina components in mammals. The autophagy protein LC3/Atg8, which is involved in autophagy membrane trafficking and substrate delivery, is present in the nucleus and directly interacts with the nuclear lamina protein lamin B1, and binds to lamin-associated domains on chromatin. This LC3-lamin B1 interaction does not downregulate lamin B1 during starvation, but mediates its degradation upon oncogenic insults, such as by activated RAS. Lamin B1 degradation is achieved by nucleus-to-cytoplasm transport that delivers lamin B1 to the lysosome. Inhibiting autophagy or the LC3-lamin B1 interaction prevents activated RAS-induced lamin B1 loss and attenuates oncogene-induced senescence in primary human cells. Our study suggests that this new function of autophagy acts as a guarding mechanism protecting cells from tumorigenesis.\",\n \"title\": \"Autophagy mediates degradation of nuclear lamina\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"34747208","text":"Mutations in the nuclear structural protein lamin A cause the premature aging syndrome Hutchinson-Gilford progeria (HGPS). Whether lamin A plays any role in normal aging is unknown. We show that the same molecular mechanism responsible for HGPS is active in healthy cells. Cell nuclei from old individuals acquire defects similar to those of HGPS patient cells, including changes in histone modifications and increased DNA damage. Age-related nuclear defects are caused by sporadic use, in healthy individuals, of the same cryptic splice site in lamin A whose constitutive activation causes HGPS. Inhibition of this splice site reverses the nuclear defects associated with aging. These observations implicate lamin A in physiological aging.","title":"Lamin A-dependent nuclear defects in human aging."},{"docid":"10518721","text":"Our eyes send different 'images' of the outside world to the brain — an image of contours (line drawing), a colour image (watercolour painting) or an image of moving objects (movie). This is commonly referred to as parallel processing, and starts as early as the first synapse of the retina, the cone pedicle. Here, the molecular composition of the transmitter receptors of the postsynaptic neurons defines which images are transferred to the inner retina. Within the second synaptic layer — the inner plexiform layer — circuits that involve complex inhibitory and excitatory interactions represent filters that select 'what the eye tells the brain'.","title":"Parallel processing in the mammalian retina"},{"docid":"22544171","text":"Hutchinson-Gilford progeria syndrome (HGPS) is a childhood premature aging disease caused by a spontaneous point mutation in lamin A (encoded by LMNA), one of the major architectural elements of the mammalian cell nucleus. The HGPS mutation activates an aberrant cryptic splice site in LMNA pre-mRNA, leading to synthesis of a truncated lamin A protein and concomitant reduction in wild-type lamin A. Fibroblasts from individuals with HGPS have severe morphological abnormalities in nuclear envelope structure. Here we show that the cellular disease phenotype is reversible in cells from individuals with HGPS. Introduction of wild-type lamin A protein does not rescue the cellular disease symptoms. The mutant LMNA mRNA and lamin A protein can be efficiently eliminated by correction of the aberrant splicing event using a modified oligonucleotide targeted to the activated cryptic splice site. Upon splicing correction, HGPS fibroblasts assume normal nuclear morphology, the aberrant nuclear distribution and cellular levels of lamina-associated proteins are rescued, defects in heterochromatin-specific histone modifications are corrected and proper expression of several misregulated genes is reestablished. Our results establish proof of principle for the correction of the premature aging phenotype in individuals with HGPS.","title":"Reversal of the cellular phenotype in the premature aging disease Hutchinson-Gilford progeria syndrome"},{"docid":"5914739","text":"The CD3ε and ζ cytoplasmic domains of the T cell receptor bind to the inner leaflet of the plasma membrane (PM), and a previous nuclear magnetic resonance structure showed that both tyrosines of the CD3ε immunoreceptor tyrosine-based activation motif partition into the bilayer. Electrostatic interactions between acidic phospholipids and clusters of basic CD3ε residues were previously shown to be essential for CD3ε and ζ membrane binding. Phosphatidylserine (PS) is the most abundant negatively charged lipid on the inner leaflet of the PM and makes a major contribution to membrane binding by the CD3ε cytoplasmic domain. Here, we show that TCR triggering by peptide--MHC complexes induces dissociation of the CD3ε cytoplasmic domain from the plasma membrane. Release of the CD3ε cytoplasmic domain from the membrane is accompanied by a substantial focal reduction in negative charge and available PS in TCR microclusters. These changes in the lipid composition of TCR microclusters even occur when TCR signaling is blocked with a Src kinase inhibitor. Local changes in the lipid composition of TCR microclusters thus render the CD3ε cytoplasmic domain accessible during early stages of T cell activation.","title":"Local changes in lipid environment of TCR microclusters regulate membrane binding by the CD3ε cytoplasmic domain"},{"docid":"15692098","text":"Hutchinson-Gilford progeria syndrome (HGPS) is a rare but well known entity characterized by extreme short stature, low body weight, early loss of hair, lipodystrophy, scleroderma, decreased joint mobility, osteolysis, and facial features that resemble aged persons. Cardiovascular compromise leads to early demise. Cognitive development is normal. Data on 10 of our own cases and 132 cases from literature are presented. The incidence in the last century in the Netherlands was 1:4,000,000. Sex ratio was 1.2:1. Main first symptoms were failure to thrive (55%), hair loss (40%), skin problems (28%), and lipodystrophy (20%). Mean age at diagnosis was 2.9 years. Growth in weight was more disturbed than growth in height, and growth delay started already prenatally. Mean height > 13 years was 109.0 cm, mean weight was 14.5 kg. Osteolysis was wide-spread but not expressed, except in the viscerocranium, and remained limited to membranous formed bone. Lipodystrophy is generalized, only intra-abdominal fat depositions remain present. Cardiovascular problems are extremely variable, both in age of onset and nature. Stroke and coronary dysfunctioning are most frequent. Pathologic findings in coronaries and aorta resemble sometimes the findings in elderly persons, but can also be much more limited. Loss of smooth muscle cells seems the most important finding. Mean age of demise was 12.6 years. Patients can be subdivided in patients with classical HGPS, which follows an autosomal dominant pattern of inheritance, (almost) all cases representing spontaneous mutations, and in non-classical progeria, in whom growth can be less retarded, scalp hair remains present for a longer time, lipodystrophy is more slowly progressive, osteolysis is more expressed except in the face, and survival well into adulthood is not uncommon. Pattern of inheritance of non-classical progeria is most probably autosomal recessive. The cause of HGPS is an abnormally formed Lamin A, either directly by a mutated LMNA gene, or through abnormal posttranslational processing (ZMPSTE24 gene mutations). Of 34 LMNA mutations found in progeria patients, there were 26 classical p. G608G mutations (76%). Pathogenesis is most likely to follow several different pathways. Potential therapeutic strategies are developed along these lines and include RNA interference techniques and inhibition of the dominant-negative influence of abnormally formed Lamin A on polymerization with normally formed Lamin A.","title":"Hutchinson-Gilford progeria syndrome: review of the phenotype"},{"docid":"7481159","text":"Gram-negative bacteria use the Type VI secretion system (T6SS) to inject toxic proteins into rival bacteria or eukaryotic cells. However, the mechanism of the T6SS is incompletely understood. In the present study, we investigated a conserved component of the T6SS, TssK, using the antibacterial T6SS of Serratia marcescens as a model system. TssK was confirmed to be essential for effector secretion by the T6SS. The native protein, although not an integral membrane protein, appeared to localize to the inner membrane, consistent with its presence within a membrane-anchored assembly. Recombinant TssK purified from S. marcescens was found to exist in several stable oligomeric forms, namely trimer, hexamer and higher-order species. Native-level purification of TssK identified TssF and TssG as interacting proteins. TssF and TssG, conserved T6SS components of unknown function, were required for T6SS activity, but not for correct localization of TssK. A complex containing TssK, TssF and TssG was subsequently purified in vitro, confirming that these three proteins form a new subcomplex within the T6SS. Our findings provide new insight into the T6SS assembly, allowing us to propose a model whereby TssK recruits TssFG into the membrane-associated T6SS complex and different oligomeric states of TssK may contribute to the dynamic mechanism of the system.","title":"Biochemical analysis of TssK, a core component of the bacterial Type VI secretion system, reveals distinct oligomeric states of TssK and identifies a TssK–TssFG subcomplex"},{"docid":"37362689","text":"The bulk of ATP consumed by various cellular processes in higher eukaryotes is normally produced by five multimeric protein complexes (I-V) embedded within the inner mitochondrial membrane, in a process known as oxidative phosphorylation (OXPHOS). Maintenance of energy homeostasis under most physiological conditions is therefore contingent upon the ability of OXPHOS to meet cellular changes in bioenergetic demand, with a chronic failure to do so being a frequent cause of human disease. With the exception of Complex II, the structural subunits of OXPHOS complexes are encoded by both the nuclear and the mitochondrial genomes. The physical separation of the two genomes necessitates that the expression of the 13 mitochondrially encoded polypeptides be co-ordinated with that of relevant nuclear-encoded partners in order to assemble functional holoenzyme complexes. Complex biogenesis is a highly ordered process, and several nuclear-encoded factors that function at distinct stages in the assembly of individual OXPHOS complexes have been identified.","title":"Oxidative phosphorylation: synthesis of mitochondrially encoded proteins and assembly of individual structural subunits into functional holoenzyme complexes."},{"docid":"4701662","text":"As phospholipids are synthesized mainly in the endoplasmic reticulum (ER) and mitochondrial inner membranes, how cells properly distribute specific phospholipids to diverse cellular membranes is a crucial problem for maintenance of organelle-specific phospholipid compositions. Although the ER-mitochondria encounter structure (ERMES) was proposed to facilitate phospholipid transfer between the ER and mitochondria, such a role of ERMES is still controversial and awaits experimental demonstration. Here we developed a novel in vitro assay system with isolated yeast membrane fractions to monitor phospholipid exchange between the ER and mitochondria. With this system, we found that phospholipid transport between the ER and mitochondria relies on membrane intactness, but not energy sources such as ATP, GTP or the membrane potential across the mitochondrial inner membrane. We further found that lack of the ERMES component impairs the phosphatidylserine transport from the ER to mitochondria, but not the phosphatidylethanolamine transport from mitochondria to the ER. This in vitro assay system thus offers a powerful tool to analyze the non-vesicular phospholipid transport between the ER and mitochondria.","title":"A phospholipid transfer function of ER-mitochondria encounter structure revealed in vitro"},{"docid":"26374799","text":"Human embryonic stem cells (hESCs) self-renew indefinitely and give rise to derivatives of all three primary germ layers, yet little is known about the signaling cascades that govern their pluripotent character. Because it plays a prominent role in the early cell fate decisions of embryonic development, we have examined the role of TGFbeta superfamily signaling in hESCs. We found that, in undifferentiated cells, the TGFbeta/activin/nodal branch is activated (through the signal transducer SMAD2/3) while the BMP/GDF branch (SMAD1/5) is only active in isolated mitotic cells. Upon early differentiation, SMAD2/3 signaling is decreased while SMAD1/5 signaling is activated. We next tested the functional role of TGFbeta/activin/nodal signaling in hESCs and found that it is required for the maintenance of markers of the undifferentiated state. We extend these findings to show that SMAD2/3 activation is required downstream of WNT signaling, which we have previously shown to be sufficient to maintain the undifferentiated state of hESCs. Strikingly, we show that in ex vivo mouse blastocyst cultures, SMAD2/3 signaling is also required to maintain the inner cell mass (from which stem cells are derived). These data reveal a crucial role for TGFbeta signaling in the earliest stages of cell fate determination and demonstrate an interconnection between TGFbeta and WNT signaling in these contexts.","title":"TGFbeta/activin/nodal signaling is necessary for the maintenance of pluripotency in human embryonic stem cells."},{"docid":"40094786","text":"Cytotoxic T lymphocytes (CTL) rapidly destroy their targets. Here we show that although target cell death occurs within 5 min of CTL-target cell contact, an immunological synapse similar to that seen in CD4 cells rapidly forms in CTL, with a ring of adhesion proteins surrounding an inner signaling molecule domain. Lytic granule secretion occurs in a separate domain within the adhesion ring, maintaining signaling protein organization during exocytosis. Live and fixed cell studies show target cell plasma membrane markers are transferred to the CTL as the cells separate. Electron microscopy reveals continuities forming membrane bridges between the CTL and target cell membranes, suggesting a possible mechanism for this transfer.","title":"The immunological synapse of CTL contains a secretory domain and membrane bridges."},{"docid":"25036988","text":"Nuclear lamin B1 (LMNB1) constitutes one of the major structural proteins in the lamina mesh. We silenced the expression of LMNB1 by RNA interference in the colon cancer cell line DLD-1 and showed a dramatic redistribution of H3K27me3 from the periphery to a more homogeneous nuclear dispersion. In addition, we observed telomere attrition and an increased frequency of micronuclei and nuclear blebs. By 3D-FISH analyses, we demonstrated that the volume and surface of chromosome territories were significantly larger in LMNB1-depleted cells, suggesting that LMNB1 is required to maintain chromatin condensation in interphase nuclei. These changes led to a prolonged S phase due to activation of Chk1. Finally, silencing of LMNB1 resulted in extensive changes in alternative splicing of multiple genes and in a higher number of enlarged nuclear speckles. Taken together, our results suggest a mechanistic role of the nuclear lamina in the organization of chromosome territories, maintenance of genome integrity and proper gene splicing.","title":"Loss of lamin B1 results in prolongation of S phase and decondensation of chromosome territories."},{"docid":"36651210","text":"Embryonic stem cells have the ability to remain undifferentiated and proliferate indefinitely in vitro while maintaining the potential to differentiate into derivatives of all three embryonic germ layers. These cells have, therefore, potential for in vitro differentiation studies, gene function, and so on. The aim of this study was to produce a human embryonic stem cell line. An inner cell mass of a human blastocyst was separated and cultured on mouse embryonic fibroblasts in embryonic stem cell medium with related additives. The established line was evaluated by morphology; passaging; freezing and thawing; alkaline phosphatase; Oct-4 expression; anti-surface markers including Tra-1-60 and Tra-1-81; and karyotype and spontaneous differentiation. Differentiated cardiomyocytes and neurons were evaluated by transmission electron microscopy and immunocytochemistry. Here, we report the derivation of a new embryonic stem cell line (Royan H1) from a human blastocyst that remains undifferentiated in morphology during continuous passaging for more than 30 passages, maintains a normal XX karyotype, is viable after freezing and thawing, and expresses alkaline phosphatase, Oct-4, Tra-1-60, and Tra-1-81. These cells remain undifferentiated when grown on mouse embryonic fibroblast feeder layers in the presence or absence of recombinant human leukemia inhibitory factor. Royan H1 cells can differentiate in vitro in the absence of feeder cells and can produce embryoid bodies that can further differentiate into beating cardiomyocytes as well as neurons. These results define Royan H1 cells as a new human embryonic stem cell line.","title":"Establishment and in vitro differentiation of a new embryonic stem cell line from human blastocyst."},{"docid":"43054703","text":"Neutrophil extracellular traps (NETs) are webs of DNA covered with antimicrobial molecules that constitute a newly described killing mechanism in innate immune defense. Previous publications reported that NETs take up to 3-4 h to form via an oxidant-dependent event that requires lytic death of neutrophils. In this study, we describe neutrophils responding uniquely to Staphylococcus aureus via a novel process of NET formation that did not require neutrophil lysis or even breach of the plasma membrane. The multilobular nucleus rapidly became rounded and condensed. During this process, we observed the separation of the inner and outer nuclear membranes and budding of vesicles, and the separated membranes and vesicles were filled with nuclear DNA. The vesicles were extruded intact into the extracellular space where they ruptured, and the chromatin was released. This entire process occurred via a unique, very rapid (5-60 min), oxidant-independent mechanism. Mitochondrial DNA constituted very little if any of these NETs. They did have a limited amount of proteolytic activity and were able to kill S. aureus. With time, the nuclear envelope ruptured, and DNA filled the cytoplasm presumably for later lytic NET production, but this was distinct from the vesicular release mechanism. Panton-Valentine leukocidin, autolysin, and a lipase were identified in supernatants with NET-inducing activity, but Panton-Valentine leukocidin was the dominant NET inducer. We describe a new mechanism of NET release that is very rapid and contributes to trapping and killing of S. aureus.","title":"A novel mechanism of rapid nuclear neutrophil extracellular trap formation in response to Staphylococcus aureus."},{"docid":"797114","text":"A recent study revealed a mechanism of delaying aging in yeast by a natural compound which specifically impacts mitochondrial redox processes. In this mechanism, exogenously added lithocholic bile acid enters yeast cells, accumulates mainly in the inner mitochondrial membrane, and elicits an age-related remodeling of phospholipid synthesis and movement within both mitochondrial membranes. Such remodeling of mitochondrial phospholipid dynamics progresses with the chronological age of a yeast cell and ultimately causes significant changes in mitochondrial membrane lipidome. These changes in the composition of membrane phospholipids alter mitochondrial abundance and morphology, thereby triggering changes in the age-related chronology of such longevity-defining redox processes as mitochondrial respiration, the maintenance of mitochondrial membrane potential, the preservation of cellular homeostasis of mitochondrially produced reactive oxygen species, and the coupling of electron transport to ATP synthesis.","title":"A mitochondrially targeted compound delays aging in yeast through a mechanism linking mitochondrial membrane lipid metabolism to mitochondrial redox biology☆"},{"docid":"29641682","text":"Pluripotent cells arise within the inner cell mass (ICM) of mammals and have the potential to generate all cell types of the adult organism through a process of commitment and ordered differentiation. Despite many decades of investigation, the mechanisms that guide and stabilise cell fate choice as well as those that can be engineered to promote its reversal, remain only partially resolved. Reprogramming of somatic cells towards a pluripotent-like state can be achieved by several different experimental routes including nuclear transfer, the supply of a defined cocktail of transcription factors, or by fusing somatic cells with a pluripotent stem cell partner. These approaches have been used to demonstrate the remarkable intrinsic epigenetic plasticity of many terminally differentiated cell types, as well as to define the factors that are required for pluripotent conversion. In this review we summarise some recent advances using cell fusion-based studies to better understand the basis of pluripotency and the epigenetic mechanisms that promote cell type inter-conversion.","title":"Reprogramming somatic cells towards pluripotency by cellular fusion."},{"docid":"3896759","text":"Blood and lymphatic vessels pervade almost all body tissues and have numerous essential roles in physiology and disease. The inner lining of these networks is formed by a single layer of endothelial cells, which is specialized according to the needs of the tissue that it supplies. Whereas the general mechanisms of blood and lymphatic vessel development are being defined with increasing molecular precision, studies of the processes of endothelial specialization remain mostly descriptive. Recent insights from genetic animal models illuminate how endothelial cells interact with each other and with their tissue environment, providing paradigms for vessel type- and organ-specific endothelial differentiation. Delineating these governing principles will be crucial for understanding how tissues develop and maintain, and how their function becomes abnormal in disease.","title":"Vascular heterogeneity and specialization in development and disease"},{"docid":"4423327","text":"Nanog is a divergent homeodomain protein found in mammalian pluripotent cells and developing germ cells. Deletion of Nanog causes early embryonic lethality, whereas constitutive expression enables autonomous self-renewal of embryonic stem cells. Nanog is accordingly considered a core element of the pluripotent transcriptional network. However, here we report that Nanog fluctuates in mouse embryonic stem cells. Transient downregulation of Nanog appears to predispose cells towards differentiation but does not mark commitment. By genetic deletion we show that, although they are prone to differentiate, embryonic stem cells can self-renew indefinitely in the permanent absence of Nanog. Expanded Nanog null cells colonize embryonic germ layers and exhibit multilineage differentiation both in fetal and adult chimaeras. Although they are also recruited to the germ line, primordial germ cells lacking Nanog fail to mature on reaching the genital ridge. This defect is rescued by repair of the mutant allele. Thus Nanog is dispensible for expression of somatic pluripotency but is specifically required for formation of germ cells. Nanog therefore acts primarily in construction of inner cell mass and germ cell states rather than in the housekeeping machinery of pluripotency. We surmise that Nanog stabilizes embryonic stem cells in culture by resisting or reversing alternative gene expression states.","title":"Nanog safeguards pluripotency and mediates germline development"},{"docid":"14446279","text":"In the yeast Saccharomyces cerevisiae that lacks lamins, the nuclear pore complex (NPC) has been proposed to serve a role in chromatin organization. Here, using fluorescence microscopy in living cells, we show that nuclear pore proteins of the Nup84 core complex, Nup84p, Nup145Cp, Nup120p, and Nup133p, serve to anchor telomere XI-L at the nuclear periphery. The integrity of this complex is shown to be required for repression of a URA3 gene inserted in the subtelomeric region of this chromosome end. Furthermore, altering the integrity of this complex decreases the efficiency of repair of a DNA double-strand break (DSB) only when it is generated in the subtelomeric region, even though the repair machinery is functional. These effects are specific to the Nup84 complex. Our observations thus confirm and extend the role played by the NPC, through the Nup84 complex, in the functional organization of chromatin. They also indicate that anchoring of telomeres is essential for efficient repair of DSBs occurring therein and is important for preserving genome integrity.","title":"Telomere tethering at the nuclear periphery is essential for efficient DNA double strand break repair in subtelomeric region"},{"docid":"1769799","text":"Transformation and conjugation permit the passage of DNA through the bacterial membranes and represent dominant modes for the transfer of genetic information between bacterial cells or between bacterial and eukaryotic cells. As such, they are responsible for the spread of fitness-enhancing traits, including antibiotic resistance. Both processes usually involve the recognition of double-stranded DNA, followed by the transfer of single strands. Elaborate molecular machines are responsible for negotiating the passage of macromolecular DNA through the layers of the cell surface. All or nearly all the machine components involved in transformation and conjugation have been identified, and here we present models for their roles in DNA transport.","title":"The ins and outs of DNA transfer in bacteria."},{"docid":"10546779","text":"Somatic cell nuclear transfer (SCNT) technology has recently been used to generate animals with a common genetic composition. In this study, we report the derivation of a pluripotent embryonic stem (ES) cell line (SCNT-hES-1) from a cloned human blastocyst. The SCNT-hES-1 cells displayed typical ES cell morphology and cell surface markers and were capable of differentiating into embryoid bodies in vitro and of forming teratomas in vivo containing cell derivatives from all three embryonic germ layers in severe combined immunodeficient mice. After continuous proliferation for more than 70 passages, SCNT-hES-1 cells maintained normal karyotypes and were genetically identical to the somatic nuclear donor cells. Although we cannot completely exclude the possibility that the cells had a parthenogenetic origin, imprinting analyses support a SCNT origin of the derived human ES cells.","title":"Evidence of a pluripotent human embryonic stem cell line derived from a cloned blastocyst."},{"docid":"7643848","text":"We have characterized the membrane topology of a 60-kDa inner membrane protein from Escherichia coli that is homologous to the recently identified Oxa1p protein in Saccharomyces cerevisiae mitochondria implicated in the assembly of mitochondrial inner membrane proteins. Hydrophobicity and alkaline phosphatase fusion analyses suggest a membrane topology with six transmembrane segments, including an N-terminal signal-anchor sequence not present in mitochondrial Oxa1p. In contrast to partial N-terminal fusion protein constructs, the full-length protein folds into a protease-resistant conformation, suggesting that important folding determinants are present in the C-terminal part of the molecule.","title":"Membrane topology of the 60-kDa Oxa1p homologue from Escherichia coli."},{"docid":"13411519","text":"Following cell surface receptor activation, the alpha subunit of the Gq subclass of GTP-binding proteins activates the phosphoinositide signalling pathway. Here we examined the expression and localization of Gq protein alpha subunits in the adult mouse brain by in situ hybridization and immunohistochemistry. Of the four members of the Gq protein alpha subunits, Galphaq and Galpha11 were transcribed predominantly in the brain. The highest transcriptional level of Galphaq was observed in cerebellar Purkinje cells (PCs) and hippocampal pyramidal cells, while that of Galpha11 was noted in hippocampal pyramidal cells. Antibody against the C-terminal peptide common to Galphaq and Galpha11 strongly labelled the cerebellar molecular layer and hippocampal neuropil layers. In these regions, immunogold preferentially labelled the cytoplasmic face of postsynaptic cell membrane of PCs and pyramidal cells. Immunoparticles were distributed along the extra-junctional cell membrane of spines, dendrites and somata, but were almost excluded from the junctional membrane. By double immunofluorescence, Galphaq/Galpha11 was extensively colocalized with metabotropic glutamate receptor mGluR1alpha in dendritic spines of PCs and with mGluR5 in those of hippocampal pyramidal cells. Together with concentrated localization of mGluR1alpha and mGluR5 in a peri-junctional annulus on PC and pyramidal cell synapses (Baude et al. 1993, Neuron, 11, 771-787; Luján et al. 1996, Eur. J. Neurosci., 8, 1488-1500), the present molecular-anatomical findings suggest that peri-junctional stimulation of the group I metabotropic glutamate receptors is mediated by Galphaq and/or Galpha11, leading to the activation of the intracellular effector, phospholipase Cbeta.","title":"Gq protein alpha subunits Galphaq and Galpha11 are localized at postsynaptic extra-junctional membrane of cerebellar Purkinje cells and hippocampal pyramidal cells."},{"docid":"37608303","text":"Cristae, the organized invaginations of the mitochondrial inner membrane, respond structurally to the energetic demands of the cell. The mechanism by which these dynamic changes are regulated and the consequences thereof are largely unknown. Optic atrophy 1 (OPA1) is the mitochondrial GTPase responsible for inner membrane fusion and maintenance of cristae structure. Here, we report that OPA1 responds dynamically to changes in energetic conditions to regulate cristae structure. This cristae regulation is independent of OPA1's role in mitochondrial fusion, since an OPA1 mutant that can still oligomerize but has no fusion activity was able to maintain cristae structure. Importantly, OPA1 was required for resistance to starvation-induced cell death, for mitochondrial respiration, for growth in galactose media and for maintenance of ATP synthase assembly, independently of its fusion activity. We identified mitochondrial solute carriers (SLC25A) as OPA1 interactors and show that their pharmacological and genetic blockade inhibited OPA1 oligomerization and function. Thus, we propose a novel way in which OPA1 senses energy substrate availability, which modulates its function in the regulation of mitochondrial architecture in a SLC25A protein-dependent manner.","title":"OPA1-dependent cristae modulation is essential for cellular adaptation to metabolic demand."},{"docid":"86129154","text":"Somatic cell nuclear transfer allows trans-acting factors present in the mammalian oocyte to reprogram somatic cell nuclei to an undifferentiated state. We show that four factors (OCT4, SOX2, NANOG, and LIN28) are sufficient to reprogram human somatic cells to pluripotent stem cells that exhibit the essential characteristics of embryonic stem (ES) cells. These induced pluripotent human stem cells have normal karyotypes, express telomerase activity, express cell surface markers and genes that characterize human ES cells, and maintain the developmental potential to differentiate into advanced derivatives of all three primary germ layers. Such induced pluripotent human cell lines should be useful in the production of new disease models and in drug development, as well as for applications in transplantation medicine, once technical limitations (for example, mutation through viral integration) are eliminated.","title":"Induced pluripotent stem cell lines derived from human somatic cells."},{"docid":"34615397","text":"The human tuberculous granuloma provides the morphological basis for local immune processes central to the outcome of tuberculosis. Because of the scarcity of information in human patients, the aim of the present study was to gain insights into the functional and structural properties of infiltrated tissue. To this end, the mycobacterial load in lesions and dissemination to different tissue locations were investigated, as well as distribution, biological functions, and interactions of host immune cells. Analysis of early granuloma formation in formerly healthy lung tissue revealed a spatio-temporal sequence of cellular infiltration to sites of mycobacterial infection. A general structure of the developing granuloma was identified, comprising an inner cell layer with few CD8(+) cells surrounding the necrotic centre and an outer area of lymphocyte infiltration harbouring mycobacteria-containing antigen-presenting cells as well as CD4(+), CD8(+), and B cells in active follicle-like centres resembling secondary lymphoid organs. It is concluded that the follicular structures in the peripheral rim of granulomas serve as a morphological substrate for the orchestration of the enduring host response in pulmonary tuberculosis.","title":"Human tuberculous granulomas induce peripheral lymphoid follicle-like structures to orchestrate local host defence in the lung."},{"docid":"22241778","text":"The human kidneys filter 180 l of blood every day via about 2.5 million glomeruli. The three layers of the glomerular filtration apparatus consist of fenestrated endothelium, specialized extracellular matrix known as the glomerular basement membrane (GBM) and the podocyte foot processes with their modified adherens junctions known as the slit diaphragm (SD). In this study we explored the contribution of podocyte beta1 integrin signaling for normal glomerular function. Mice with podocyte specific deletion of integrin beta1 (podocin-Cre beta1-fl/fl mice) are born normal but cannot complete postnatal renal development. They exhibit detectable proteinuria on day 1 and die within a week. The kidneys of podocin-Cre beta1-fl/fl mice exhibit normal glomerular endothelium but show severe GBM defects with multilaminations and splitting including podocyte foot process effacement. The integrin linked kinase (ILK) is a downstream mediator of integrin beta1 activity in epithelial cells. To further explore whether integrin beta1-mediated signaling facilitates proper glomerular filtration, we generated mice deficient of ILK in the podocytes (podocin-Cre ILK-fl/fl mice). These mice develop normally but exhibit postnatal proteinuria at birth and die within 15 weeks of age due to renal failure. Collectively, our studies demonstrate that podocyte beta1 integrin and ILK signaling is critical for postnatal development and function of the glomerular filtration apparatus.","title":"Integrin beta1-mediated matrix assembly and signaling are critical for the normal development and function of the kidney glomerulus."},{"docid":"6308416","text":"Coordinated cell movements in epithelial layers are essential for proper tissue morphogenesis and homeostasis, but our understanding of the mechanisms that coordinate the behavior of multiple cells in these processes is far from complete. Recent experiments with Madin-Darby canine kidney epithelial monolayers revealed a wave-like pattern of injury-induced MAPK activation and showed that it is essential for collective cell migration after wounding. To investigate the effects of the different aspects of wounding on cell sheet migration, we engineered a system that allowed us to dissect the classic wound healing assay. We studied Madin-Darby canine kidney sheet migration under three different conditions: 1) the classic wound healing assay, 2) empty space induction, where a confluent monolayer is grown adjacent to a slab of polydimethylsiloxane and the monolayer is not injured but allowed to migrate upon removal of the slab, and 3) injury via polydimethylsiloxane membrane peel-off, where an injured monolayer migrates onto plain tissue culture surface, as in the case of empty space induction allowing for direct comparison. By tracking the motion of individual cells within the sheet under these three conditions, we show how the dynamics of the individual cells' motion is responsible for the coordinated migration of the sheet and is coordinated with the activation of ERK1/2 MAPK. In addition, we demonstrate that the propagation of the waves of MAPK activation depends on the generation of reactive oxygen species at the wound edge.","title":"Role of boundary conditions in an experimental model of epithelial wound healing."},{"docid":"26283293","text":"Eukaryotic cells are compartmentalized into membrane-bounded organelles whose functions rely on lipid trafficking to achieve membrane-specific compositions of lipids. Here we focused on the Ups1-Mdm35 system, which mediates phosphatidic acid (PA) transfer between the outer and inner mitochondrial membranes, and determined the X-ray structures of Mdm35 and Ups1-Mdm35 with and without PA. The Ups1-Mdm35 complex constitutes a single domain that has a deep pocket and flexible Ω-loop lid. Structure-based mutational analyses revealed that a basic residue at the pocket bottom and the Ω-loop lid are important for PA extraction from the membrane following Ups1 binding. Ups1 binding to the membrane is enhanced by the dissociation of Mdm35. We also show that basic residues around the pocket entrance are important for Ups1 binding to the membrane and PA extraction. These results provide a structural basis for understanding the mechanism of PA transfer between mitochondrial membranes.","title":"Structural and mechanistic insights into phospholipid transfer by Ups1–Mdm35 in mitochondria"},{"docid":"8247597","text":"Mutations and deletions in the mitochondrial genome (mtDNA), as well as instability of the nuclear genome, are involved in multiple human diseases. Here, we report that in Saccharomyces cerevisiae, loss of mtDNA leads to nuclear genome instability, through a process of cell-cycle arrest and selection we define as a cellular crisis. This crisis is not mediated by the absence of respiration, but instead correlates with a reduction in the mitochondrial membrane potential. Analysis of cells undergoing this crisis identified a defect in iron-sulfur cluster (ISC) biogenesis, which requires normal mitochondrial function. We found that downregulation of nonmitochondrial ISC protein biogenesis was sufficient to cause increased genomic instability in cells with intact mitochondrial function. These results suggest mitochondrial dysfunction stimulates nuclear genome instability by inhibiting the production of ISC-containing protein(s), which are required for maintenance of nuclear genome integrity. For a video summary of this article, see the PaperFlick file available with the online Supplemental Data.","title":"Mitochondrial Dysfunction Leads to Nuclear Genome Instability via an Iron-Sulfur Cluster Defect"},{"docid":"4447055","text":"Contusive spinal cord injury leads to a variety of disabilities owing to limited neuronal regeneration and functional plasticity. It is well established that an upregulation of glial-derived chondroitin sulphate proteoglycans (CSPGs) within the glial scar and perineuronal net creates a barrier to axonal regrowth and sprouting. Protein tyrosine phosphatase σ (PTPσ), along with its sister phosphatase leukocyte common antigen-related (LAR) and the nogo receptors 1 and 3 (NgR), have recently been identified as receptors for the inhibitory glycosylated side chains of CSPGs. Here we find in rats that PTPσ has a critical role in converting growth cones into a dystrophic state by tightly stabilizing them within CSPG-rich substrates. We generated a membrane-permeable peptide mimetic of the PTPσ wedge domain that binds to PTPσ and relieves CSPG-mediated inhibition. Systemic delivery of this peptide over weeks restored substantial serotonergic innervation to the spinal cord below the level of injury and facilitated functional recovery of both locomotor and urinary systems. Our results add a new layer of understanding to the critical role of PTPσ in mediating the growth-inhibited state of neurons due to CSPGs within the injured adult spinal cord.","title":"Modulation of the proteoglycan receptor PTPσ promotes recovery after spinal cord injury"}],"string":"[\n {\n \"docid\": \"34747208\",\n \"text\": \"Mutations in the nuclear structural protein lamin A cause the premature aging syndrome Hutchinson-Gilford progeria (HGPS). Whether lamin A plays any role in normal aging is unknown. We show that the same molecular mechanism responsible for HGPS is active in healthy cells. Cell nuclei from old individuals acquire defects similar to those of HGPS patient cells, including changes in histone modifications and increased DNA damage. Age-related nuclear defects are caused by sporadic use, in healthy individuals, of the same cryptic splice site in lamin A whose constitutive activation causes HGPS. Inhibition of this splice site reverses the nuclear defects associated with aging. These observations implicate lamin A in physiological aging.\",\n \"title\": \"Lamin A-dependent nuclear defects in human aging.\"\n },\n {\n \"docid\": \"10518721\",\n \"text\": \"Our eyes send different 'images' of the outside world to the brain — an image of contours (line drawing), a colour image (watercolour painting) or an image of moving objects (movie). This is commonly referred to as parallel processing, and starts as early as the first synapse of the retina, the cone pedicle. Here, the molecular composition of the transmitter receptors of the postsynaptic neurons defines which images are transferred to the inner retina. Within the second synaptic layer — the inner plexiform layer — circuits that involve complex inhibitory and excitatory interactions represent filters that select 'what the eye tells the brain'.\",\n \"title\": \"Parallel processing in the mammalian retina\"\n },\n {\n \"docid\": \"22544171\",\n \"text\": \"Hutchinson-Gilford progeria syndrome (HGPS) is a childhood premature aging disease caused by a spontaneous point mutation in lamin A (encoded by LMNA), one of the major architectural elements of the mammalian cell nucleus. The HGPS mutation activates an aberrant cryptic splice site in LMNA pre-mRNA, leading to synthesis of a truncated lamin A protein and concomitant reduction in wild-type lamin A. Fibroblasts from individuals with HGPS have severe morphological abnormalities in nuclear envelope structure. Here we show that the cellular disease phenotype is reversible in cells from individuals with HGPS. Introduction of wild-type lamin A protein does not rescue the cellular disease symptoms. The mutant LMNA mRNA and lamin A protein can be efficiently eliminated by correction of the aberrant splicing event using a modified oligonucleotide targeted to the activated cryptic splice site. Upon splicing correction, HGPS fibroblasts assume normal nuclear morphology, the aberrant nuclear distribution and cellular levels of lamina-associated proteins are rescued, defects in heterochromatin-specific histone modifications are corrected and proper expression of several misregulated genes is reestablished. Our results establish proof of principle for the correction of the premature aging phenotype in individuals with HGPS.\",\n \"title\": \"Reversal of the cellular phenotype in the premature aging disease Hutchinson-Gilford progeria syndrome\"\n },\n {\n \"docid\": \"5914739\",\n \"text\": \"The CD3ε and ζ cytoplasmic domains of the T cell receptor bind to the inner leaflet of the plasma membrane (PM), and a previous nuclear magnetic resonance structure showed that both tyrosines of the CD3ε immunoreceptor tyrosine-based activation motif partition into the bilayer. Electrostatic interactions between acidic phospholipids and clusters of basic CD3ε residues were previously shown to be essential for CD3ε and ζ membrane binding. Phosphatidylserine (PS) is the most abundant negatively charged lipid on the inner leaflet of the PM and makes a major contribution to membrane binding by the CD3ε cytoplasmic domain. Here, we show that TCR triggering by peptide--MHC complexes induces dissociation of the CD3ε cytoplasmic domain from the plasma membrane. Release of the CD3ε cytoplasmic domain from the membrane is accompanied by a substantial focal reduction in negative charge and available PS in TCR microclusters. These changes in the lipid composition of TCR microclusters even occur when TCR signaling is blocked with a Src kinase inhibitor. Local changes in the lipid composition of TCR microclusters thus render the CD3ε cytoplasmic domain accessible during early stages of T cell activation.\",\n \"title\": \"Local changes in lipid environment of TCR microclusters regulate membrane binding by the CD3ε cytoplasmic domain\"\n },\n {\n \"docid\": \"15692098\",\n \"text\": \"Hutchinson-Gilford progeria syndrome (HGPS) is a rare but well known entity characterized by extreme short stature, low body weight, early loss of hair, lipodystrophy, scleroderma, decreased joint mobility, osteolysis, and facial features that resemble aged persons. Cardiovascular compromise leads to early demise. Cognitive development is normal. Data on 10 of our own cases and 132 cases from literature are presented. The incidence in the last century in the Netherlands was 1:4,000,000. Sex ratio was 1.2:1. Main first symptoms were failure to thrive (55%), hair loss (40%), skin problems (28%), and lipodystrophy (20%). Mean age at diagnosis was 2.9 years. Growth in weight was more disturbed than growth in height, and growth delay started already prenatally. Mean height > 13 years was 109.0 cm, mean weight was 14.5 kg. Osteolysis was wide-spread but not expressed, except in the viscerocranium, and remained limited to membranous formed bone. Lipodystrophy is generalized, only intra-abdominal fat depositions remain present. Cardiovascular problems are extremely variable, both in age of onset and nature. Stroke and coronary dysfunctioning are most frequent. Pathologic findings in coronaries and aorta resemble sometimes the findings in elderly persons, but can also be much more limited. Loss of smooth muscle cells seems the most important finding. Mean age of demise was 12.6 years. Patients can be subdivided in patients with classical HGPS, which follows an autosomal dominant pattern of inheritance, (almost) all cases representing spontaneous mutations, and in non-classical progeria, in whom growth can be less retarded, scalp hair remains present for a longer time, lipodystrophy is more slowly progressive, osteolysis is more expressed except in the face, and survival well into adulthood is not uncommon. Pattern of inheritance of non-classical progeria is most probably autosomal recessive. The cause of HGPS is an abnormally formed Lamin A, either directly by a mutated LMNA gene, or through abnormal posttranslational processing (ZMPSTE24 gene mutations). Of 34 LMNA mutations found in progeria patients, there were 26 classical p. G608G mutations (76%). Pathogenesis is most likely to follow several different pathways. Potential therapeutic strategies are developed along these lines and include RNA interference techniques and inhibition of the dominant-negative influence of abnormally formed Lamin A on polymerization with normally formed Lamin A.\",\n \"title\": \"Hutchinson-Gilford progeria syndrome: review of the phenotype\"\n },\n {\n \"docid\": \"7481159\",\n \"text\": \"Gram-negative bacteria use the Type VI secretion system (T6SS) to inject toxic proteins into rival bacteria or eukaryotic cells. However, the mechanism of the T6SS is incompletely understood. In the present study, we investigated a conserved component of the T6SS, TssK, using the antibacterial T6SS of Serratia marcescens as a model system. TssK was confirmed to be essential for effector secretion by the T6SS. The native protein, although not an integral membrane protein, appeared to localize to the inner membrane, consistent with its presence within a membrane-anchored assembly. Recombinant TssK purified from S. marcescens was found to exist in several stable oligomeric forms, namely trimer, hexamer and higher-order species. Native-level purification of TssK identified TssF and TssG as interacting proteins. TssF and TssG, conserved T6SS components of unknown function, were required for T6SS activity, but not for correct localization of TssK. A complex containing TssK, TssF and TssG was subsequently purified in vitro, confirming that these three proteins form a new subcomplex within the T6SS. Our findings provide new insight into the T6SS assembly, allowing us to propose a model whereby TssK recruits TssFG into the membrane-associated T6SS complex and different oligomeric states of TssK may contribute to the dynamic mechanism of the system.\",\n \"title\": \"Biochemical analysis of TssK, a core component of the bacterial Type VI secretion system, reveals distinct oligomeric states of TssK and identifies a TssK–TssFG subcomplex\"\n },\n {\n \"docid\": \"37362689\",\n \"text\": \"The bulk of ATP consumed by various cellular processes in higher eukaryotes is normally produced by five multimeric protein complexes (I-V) embedded within the inner mitochondrial membrane, in a process known as oxidative phosphorylation (OXPHOS). Maintenance of energy homeostasis under most physiological conditions is therefore contingent upon the ability of OXPHOS to meet cellular changes in bioenergetic demand, with a chronic failure to do so being a frequent cause of human disease. With the exception of Complex II, the structural subunits of OXPHOS complexes are encoded by both the nuclear and the mitochondrial genomes. The physical separation of the two genomes necessitates that the expression of the 13 mitochondrially encoded polypeptides be co-ordinated with that of relevant nuclear-encoded partners in order to assemble functional holoenzyme complexes. Complex biogenesis is a highly ordered process, and several nuclear-encoded factors that function at distinct stages in the assembly of individual OXPHOS complexes have been identified.\",\n \"title\": \"Oxidative phosphorylation: synthesis of mitochondrially encoded proteins and assembly of individual structural subunits into functional holoenzyme complexes.\"\n },\n {\n \"docid\": \"4701662\",\n \"text\": \"As phospholipids are synthesized mainly in the endoplasmic reticulum (ER) and mitochondrial inner membranes, how cells properly distribute specific phospholipids to diverse cellular membranes is a crucial problem for maintenance of organelle-specific phospholipid compositions. Although the ER-mitochondria encounter structure (ERMES) was proposed to facilitate phospholipid transfer between the ER and mitochondria, such a role of ERMES is still controversial and awaits experimental demonstration. Here we developed a novel in vitro assay system with isolated yeast membrane fractions to monitor phospholipid exchange between the ER and mitochondria. With this system, we found that phospholipid transport between the ER and mitochondria relies on membrane intactness, but not energy sources such as ATP, GTP or the membrane potential across the mitochondrial inner membrane. We further found that lack of the ERMES component impairs the phosphatidylserine transport from the ER to mitochondria, but not the phosphatidylethanolamine transport from mitochondria to the ER. This in vitro assay system thus offers a powerful tool to analyze the non-vesicular phospholipid transport between the ER and mitochondria.\",\n \"title\": \"A phospholipid transfer function of ER-mitochondria encounter structure revealed in vitro\"\n },\n {\n \"docid\": \"26374799\",\n \"text\": \"Human embryonic stem cells (hESCs) self-renew indefinitely and give rise to derivatives of all three primary germ layers, yet little is known about the signaling cascades that govern their pluripotent character. Because it plays a prominent role in the early cell fate decisions of embryonic development, we have examined the role of TGFbeta superfamily signaling in hESCs. We found that, in undifferentiated cells, the TGFbeta/activin/nodal branch is activated (through the signal transducer SMAD2/3) while the BMP/GDF branch (SMAD1/5) is only active in isolated mitotic cells. Upon early differentiation, SMAD2/3 signaling is decreased while SMAD1/5 signaling is activated. We next tested the functional role of TGFbeta/activin/nodal signaling in hESCs and found that it is required for the maintenance of markers of the undifferentiated state. We extend these findings to show that SMAD2/3 activation is required downstream of WNT signaling, which we have previously shown to be sufficient to maintain the undifferentiated state of hESCs. Strikingly, we show that in ex vivo mouse blastocyst cultures, SMAD2/3 signaling is also required to maintain the inner cell mass (from which stem cells are derived). These data reveal a crucial role for TGFbeta signaling in the earliest stages of cell fate determination and demonstrate an interconnection between TGFbeta and WNT signaling in these contexts.\",\n \"title\": \"TGFbeta/activin/nodal signaling is necessary for the maintenance of pluripotency in human embryonic stem cells.\"\n },\n {\n \"docid\": \"40094786\",\n \"text\": \"Cytotoxic T lymphocytes (CTL) rapidly destroy their targets. Here we show that although target cell death occurs within 5 min of CTL-target cell contact, an immunological synapse similar to that seen in CD4 cells rapidly forms in CTL, with a ring of adhesion proteins surrounding an inner signaling molecule domain. Lytic granule secretion occurs in a separate domain within the adhesion ring, maintaining signaling protein organization during exocytosis. Live and fixed cell studies show target cell plasma membrane markers are transferred to the CTL as the cells separate. Electron microscopy reveals continuities forming membrane bridges between the CTL and target cell membranes, suggesting a possible mechanism for this transfer.\",\n \"title\": \"The immunological synapse of CTL contains a secretory domain and membrane bridges.\"\n },\n {\n \"docid\": \"25036988\",\n \"text\": \"Nuclear lamin B1 (LMNB1) constitutes one of the major structural proteins in the lamina mesh. We silenced the expression of LMNB1 by RNA interference in the colon cancer cell line DLD-1 and showed a dramatic redistribution of H3K27me3 from the periphery to a more homogeneous nuclear dispersion. In addition, we observed telomere attrition and an increased frequency of micronuclei and nuclear blebs. By 3D-FISH analyses, we demonstrated that the volume and surface of chromosome territories were significantly larger in LMNB1-depleted cells, suggesting that LMNB1 is required to maintain chromatin condensation in interphase nuclei. These changes led to a prolonged S phase due to activation of Chk1. Finally, silencing of LMNB1 resulted in extensive changes in alternative splicing of multiple genes and in a higher number of enlarged nuclear speckles. Taken together, our results suggest a mechanistic role of the nuclear lamina in the organization of chromosome territories, maintenance of genome integrity and proper gene splicing.\",\n \"title\": \"Loss of lamin B1 results in prolongation of S phase and decondensation of chromosome territories.\"\n },\n {\n \"docid\": \"36651210\",\n \"text\": \"Embryonic stem cells have the ability to remain undifferentiated and proliferate indefinitely in vitro while maintaining the potential to differentiate into derivatives of all three embryonic germ layers. These cells have, therefore, potential for in vitro differentiation studies, gene function, and so on. The aim of this study was to produce a human embryonic stem cell line. An inner cell mass of a human blastocyst was separated and cultured on mouse embryonic fibroblasts in embryonic stem cell medium with related additives. The established line was evaluated by morphology; passaging; freezing and thawing; alkaline phosphatase; Oct-4 expression; anti-surface markers including Tra-1-60 and Tra-1-81; and karyotype and spontaneous differentiation. Differentiated cardiomyocytes and neurons were evaluated by transmission electron microscopy and immunocytochemistry. Here, we report the derivation of a new embryonic stem cell line (Royan H1) from a human blastocyst that remains undifferentiated in morphology during continuous passaging for more than 30 passages, maintains a normal XX karyotype, is viable after freezing and thawing, and expresses alkaline phosphatase, Oct-4, Tra-1-60, and Tra-1-81. These cells remain undifferentiated when grown on mouse embryonic fibroblast feeder layers in the presence or absence of recombinant human leukemia inhibitory factor. Royan H1 cells can differentiate in vitro in the absence of feeder cells and can produce embryoid bodies that can further differentiate into beating cardiomyocytes as well as neurons. These results define Royan H1 cells as a new human embryonic stem cell line.\",\n \"title\": \"Establishment and in vitro differentiation of a new embryonic stem cell line from human blastocyst.\"\n },\n {\n \"docid\": \"43054703\",\n \"text\": \"Neutrophil extracellular traps (NETs) are webs of DNA covered with antimicrobial molecules that constitute a newly described killing mechanism in innate immune defense. Previous publications reported that NETs take up to 3-4 h to form via an oxidant-dependent event that requires lytic death of neutrophils. In this study, we describe neutrophils responding uniquely to Staphylococcus aureus via a novel process of NET formation that did not require neutrophil lysis or even breach of the plasma membrane. The multilobular nucleus rapidly became rounded and condensed. During this process, we observed the separation of the inner and outer nuclear membranes and budding of vesicles, and the separated membranes and vesicles were filled with nuclear DNA. The vesicles were extruded intact into the extracellular space where they ruptured, and the chromatin was released. This entire process occurred via a unique, very rapid (5-60 min), oxidant-independent mechanism. Mitochondrial DNA constituted very little if any of these NETs. They did have a limited amount of proteolytic activity and were able to kill S. aureus. With time, the nuclear envelope ruptured, and DNA filled the cytoplasm presumably for later lytic NET production, but this was distinct from the vesicular release mechanism. Panton-Valentine leukocidin, autolysin, and a lipase were identified in supernatants with NET-inducing activity, but Panton-Valentine leukocidin was the dominant NET inducer. We describe a new mechanism of NET release that is very rapid and contributes to trapping and killing of S. aureus.\",\n \"title\": \"A novel mechanism of rapid nuclear neutrophil extracellular trap formation in response to Staphylococcus aureus.\"\n },\n {\n \"docid\": \"797114\",\n \"text\": \"A recent study revealed a mechanism of delaying aging in yeast by a natural compound which specifically impacts mitochondrial redox processes. In this mechanism, exogenously added lithocholic bile acid enters yeast cells, accumulates mainly in the inner mitochondrial membrane, and elicits an age-related remodeling of phospholipid synthesis and movement within both mitochondrial membranes. Such remodeling of mitochondrial phospholipid dynamics progresses with the chronological age of a yeast cell and ultimately causes significant changes in mitochondrial membrane lipidome. These changes in the composition of membrane phospholipids alter mitochondrial abundance and morphology, thereby triggering changes in the age-related chronology of such longevity-defining redox processes as mitochondrial respiration, the maintenance of mitochondrial membrane potential, the preservation of cellular homeostasis of mitochondrially produced reactive oxygen species, and the coupling of electron transport to ATP synthesis.\",\n \"title\": \"A mitochondrially targeted compound delays aging in yeast through a mechanism linking mitochondrial membrane lipid metabolism to mitochondrial redox biology☆\"\n },\n {\n \"docid\": \"29641682\",\n \"text\": \"Pluripotent cells arise within the inner cell mass (ICM) of mammals and have the potential to generate all cell types of the adult organism through a process of commitment and ordered differentiation. Despite many decades of investigation, the mechanisms that guide and stabilise cell fate choice as well as those that can be engineered to promote its reversal, remain only partially resolved. Reprogramming of somatic cells towards a pluripotent-like state can be achieved by several different experimental routes including nuclear transfer, the supply of a defined cocktail of transcription factors, or by fusing somatic cells with a pluripotent stem cell partner. These approaches have been used to demonstrate the remarkable intrinsic epigenetic plasticity of many terminally differentiated cell types, as well as to define the factors that are required for pluripotent conversion. In this review we summarise some recent advances using cell fusion-based studies to better understand the basis of pluripotency and the epigenetic mechanisms that promote cell type inter-conversion.\",\n \"title\": \"Reprogramming somatic cells towards pluripotency by cellular fusion.\"\n },\n {\n \"docid\": \"3896759\",\n \"text\": \"Blood and lymphatic vessels pervade almost all body tissues and have numerous essential roles in physiology and disease. The inner lining of these networks is formed by a single layer of endothelial cells, which is specialized according to the needs of the tissue that it supplies. Whereas the general mechanisms of blood and lymphatic vessel development are being defined with increasing molecular precision, studies of the processes of endothelial specialization remain mostly descriptive. Recent insights from genetic animal models illuminate how endothelial cells interact with each other and with their tissue environment, providing paradigms for vessel type- and organ-specific endothelial differentiation. Delineating these governing principles will be crucial for understanding how tissues develop and maintain, and how their function becomes abnormal in disease.\",\n \"title\": \"Vascular heterogeneity and specialization in development and disease\"\n },\n {\n \"docid\": \"4423327\",\n \"text\": \"Nanog is a divergent homeodomain protein found in mammalian pluripotent cells and developing germ cells. Deletion of Nanog causes early embryonic lethality, whereas constitutive expression enables autonomous self-renewal of embryonic stem cells. Nanog is accordingly considered a core element of the pluripotent transcriptional network. However, here we report that Nanog fluctuates in mouse embryonic stem cells. Transient downregulation of Nanog appears to predispose cells towards differentiation but does not mark commitment. By genetic deletion we show that, although they are prone to differentiate, embryonic stem cells can self-renew indefinitely in the permanent absence of Nanog. Expanded Nanog null cells colonize embryonic germ layers and exhibit multilineage differentiation both in fetal and adult chimaeras. Although they are also recruited to the germ line, primordial germ cells lacking Nanog fail to mature on reaching the genital ridge. This defect is rescued by repair of the mutant allele. Thus Nanog is dispensible for expression of somatic pluripotency but is specifically required for formation of germ cells. Nanog therefore acts primarily in construction of inner cell mass and germ cell states rather than in the housekeeping machinery of pluripotency. We surmise that Nanog stabilizes embryonic stem cells in culture by resisting or reversing alternative gene expression states.\",\n \"title\": \"Nanog safeguards pluripotency and mediates germline development\"\n },\n {\n \"docid\": \"14446279\",\n \"text\": \"In the yeast Saccharomyces cerevisiae that lacks lamins, the nuclear pore complex (NPC) has been proposed to serve a role in chromatin organization. Here, using fluorescence microscopy in living cells, we show that nuclear pore proteins of the Nup84 core complex, Nup84p, Nup145Cp, Nup120p, and Nup133p, serve to anchor telomere XI-L at the nuclear periphery. The integrity of this complex is shown to be required for repression of a URA3 gene inserted in the subtelomeric region of this chromosome end. Furthermore, altering the integrity of this complex decreases the efficiency of repair of a DNA double-strand break (DSB) only when it is generated in the subtelomeric region, even though the repair machinery is functional. These effects are specific to the Nup84 complex. Our observations thus confirm and extend the role played by the NPC, through the Nup84 complex, in the functional organization of chromatin. They also indicate that anchoring of telomeres is essential for efficient repair of DSBs occurring therein and is important for preserving genome integrity.\",\n \"title\": \"Telomere tethering at the nuclear periphery is essential for efficient DNA double strand break repair in subtelomeric region\"\n },\n {\n \"docid\": \"1769799\",\n \"text\": \"Transformation and conjugation permit the passage of DNA through the bacterial membranes and represent dominant modes for the transfer of genetic information between bacterial cells or between bacterial and eukaryotic cells. As such, they are responsible for the spread of fitness-enhancing traits, including antibiotic resistance. Both processes usually involve the recognition of double-stranded DNA, followed by the transfer of single strands. Elaborate molecular machines are responsible for negotiating the passage of macromolecular DNA through the layers of the cell surface. All or nearly all the machine components involved in transformation and conjugation have been identified, and here we present models for their roles in DNA transport.\",\n \"title\": \"The ins and outs of DNA transfer in bacteria.\"\n },\n {\n \"docid\": \"10546779\",\n \"text\": \"Somatic cell nuclear transfer (SCNT) technology has recently been used to generate animals with a common genetic composition. In this study, we report the derivation of a pluripotent embryonic stem (ES) cell line (SCNT-hES-1) from a cloned human blastocyst. The SCNT-hES-1 cells displayed typical ES cell morphology and cell surface markers and were capable of differentiating into embryoid bodies in vitro and of forming teratomas in vivo containing cell derivatives from all three embryonic germ layers in severe combined immunodeficient mice. After continuous proliferation for more than 70 passages, SCNT-hES-1 cells maintained normal karyotypes and were genetically identical to the somatic nuclear donor cells. Although we cannot completely exclude the possibility that the cells had a parthenogenetic origin, imprinting analyses support a SCNT origin of the derived human ES cells.\",\n \"title\": \"Evidence of a pluripotent human embryonic stem cell line derived from a cloned blastocyst.\"\n },\n {\n \"docid\": \"7643848\",\n \"text\": \"We have characterized the membrane topology of a 60-kDa inner membrane protein from Escherichia coli that is homologous to the recently identified Oxa1p protein in Saccharomyces cerevisiae mitochondria implicated in the assembly of mitochondrial inner membrane proteins. Hydrophobicity and alkaline phosphatase fusion analyses suggest a membrane topology with six transmembrane segments, including an N-terminal signal-anchor sequence not present in mitochondrial Oxa1p. In contrast to partial N-terminal fusion protein constructs, the full-length protein folds into a protease-resistant conformation, suggesting that important folding determinants are present in the C-terminal part of the molecule.\",\n \"title\": \"Membrane topology of the 60-kDa Oxa1p homologue from Escherichia coli.\"\n },\n {\n \"docid\": \"13411519\",\n \"text\": \"Following cell surface receptor activation, the alpha subunit of the Gq subclass of GTP-binding proteins activates the phosphoinositide signalling pathway. Here we examined the expression and localization of Gq protein alpha subunits in the adult mouse brain by in situ hybridization and immunohistochemistry. Of the four members of the Gq protein alpha subunits, Galphaq and Galpha11 were transcribed predominantly in the brain. The highest transcriptional level of Galphaq was observed in cerebellar Purkinje cells (PCs) and hippocampal pyramidal cells, while that of Galpha11 was noted in hippocampal pyramidal cells. Antibody against the C-terminal peptide common to Galphaq and Galpha11 strongly labelled the cerebellar molecular layer and hippocampal neuropil layers. In these regions, immunogold preferentially labelled the cytoplasmic face of postsynaptic cell membrane of PCs and pyramidal cells. Immunoparticles were distributed along the extra-junctional cell membrane of spines, dendrites and somata, but were almost excluded from the junctional membrane. By double immunofluorescence, Galphaq/Galpha11 was extensively colocalized with metabotropic glutamate receptor mGluR1alpha in dendritic spines of PCs and with mGluR5 in those of hippocampal pyramidal cells. Together with concentrated localization of mGluR1alpha and mGluR5 in a peri-junctional annulus on PC and pyramidal cell synapses (Baude et al. 1993, Neuron, 11, 771-787; Luján et al. 1996, Eur. J. Neurosci., 8, 1488-1500), the present molecular-anatomical findings suggest that peri-junctional stimulation of the group I metabotropic glutamate receptors is mediated by Galphaq and/or Galpha11, leading to the activation of the intracellular effector, phospholipase Cbeta.\",\n \"title\": \"Gq protein alpha subunits Galphaq and Galpha11 are localized at postsynaptic extra-junctional membrane of cerebellar Purkinje cells and hippocampal pyramidal cells.\"\n },\n {\n \"docid\": \"37608303\",\n \"text\": \"Cristae, the organized invaginations of the mitochondrial inner membrane, respond structurally to the energetic demands of the cell. The mechanism by which these dynamic changes are regulated and the consequences thereof are largely unknown. Optic atrophy 1 (OPA1) is the mitochondrial GTPase responsible for inner membrane fusion and maintenance of cristae structure. Here, we report that OPA1 responds dynamically to changes in energetic conditions to regulate cristae structure. This cristae regulation is independent of OPA1's role in mitochondrial fusion, since an OPA1 mutant that can still oligomerize but has no fusion activity was able to maintain cristae structure. Importantly, OPA1 was required for resistance to starvation-induced cell death, for mitochondrial respiration, for growth in galactose media and for maintenance of ATP synthase assembly, independently of its fusion activity. We identified mitochondrial solute carriers (SLC25A) as OPA1 interactors and show that their pharmacological and genetic blockade inhibited OPA1 oligomerization and function. Thus, we propose a novel way in which OPA1 senses energy substrate availability, which modulates its function in the regulation of mitochondrial architecture in a SLC25A protein-dependent manner.\",\n \"title\": \"OPA1-dependent cristae modulation is essential for cellular adaptation to metabolic demand.\"\n },\n {\n \"docid\": \"86129154\",\n \"text\": \"Somatic cell nuclear transfer allows trans-acting factors present in the mammalian oocyte to reprogram somatic cell nuclei to an undifferentiated state. We show that four factors (OCT4, SOX2, NANOG, and LIN28) are sufficient to reprogram human somatic cells to pluripotent stem cells that exhibit the essential characteristics of embryonic stem (ES) cells. These induced pluripotent human stem cells have normal karyotypes, express telomerase activity, express cell surface markers and genes that characterize human ES cells, and maintain the developmental potential to differentiate into advanced derivatives of all three primary germ layers. Such induced pluripotent human cell lines should be useful in the production of new disease models and in drug development, as well as for applications in transplantation medicine, once technical limitations (for example, mutation through viral integration) are eliminated.\",\n \"title\": \"Induced pluripotent stem cell lines derived from human somatic cells.\"\n },\n {\n \"docid\": \"34615397\",\n \"text\": \"The human tuberculous granuloma provides the morphological basis for local immune processes central to the outcome of tuberculosis. Because of the scarcity of information in human patients, the aim of the present study was to gain insights into the functional and structural properties of infiltrated tissue. To this end, the mycobacterial load in lesions and dissemination to different tissue locations were investigated, as well as distribution, biological functions, and interactions of host immune cells. Analysis of early granuloma formation in formerly healthy lung tissue revealed a spatio-temporal sequence of cellular infiltration to sites of mycobacterial infection. A general structure of the developing granuloma was identified, comprising an inner cell layer with few CD8(+) cells surrounding the necrotic centre and an outer area of lymphocyte infiltration harbouring mycobacteria-containing antigen-presenting cells as well as CD4(+), CD8(+), and B cells in active follicle-like centres resembling secondary lymphoid organs. It is concluded that the follicular structures in the peripheral rim of granulomas serve as a morphological substrate for the orchestration of the enduring host response in pulmonary tuberculosis.\",\n \"title\": \"Human tuberculous granulomas induce peripheral lymphoid follicle-like structures to orchestrate local host defence in the lung.\"\n },\n {\n \"docid\": \"22241778\",\n \"text\": \"The human kidneys filter 180 l of blood every day via about 2.5 million glomeruli. The three layers of the glomerular filtration apparatus consist of fenestrated endothelium, specialized extracellular matrix known as the glomerular basement membrane (GBM) and the podocyte foot processes with their modified adherens junctions known as the slit diaphragm (SD). In this study we explored the contribution of podocyte beta1 integrin signaling for normal glomerular function. Mice with podocyte specific deletion of integrin beta1 (podocin-Cre beta1-fl/fl mice) are born normal but cannot complete postnatal renal development. They exhibit detectable proteinuria on day 1 and die within a week. The kidneys of podocin-Cre beta1-fl/fl mice exhibit normal glomerular endothelium but show severe GBM defects with multilaminations and splitting including podocyte foot process effacement. The integrin linked kinase (ILK) is a downstream mediator of integrin beta1 activity in epithelial cells. To further explore whether integrin beta1-mediated signaling facilitates proper glomerular filtration, we generated mice deficient of ILK in the podocytes (podocin-Cre ILK-fl/fl mice). These mice develop normally but exhibit postnatal proteinuria at birth and die within 15 weeks of age due to renal failure. Collectively, our studies demonstrate that podocyte beta1 integrin and ILK signaling is critical for postnatal development and function of the glomerular filtration apparatus.\",\n \"title\": \"Integrin beta1-mediated matrix assembly and signaling are critical for the normal development and function of the kidney glomerulus.\"\n },\n {\n \"docid\": \"6308416\",\n \"text\": \"Coordinated cell movements in epithelial layers are essential for proper tissue morphogenesis and homeostasis, but our understanding of the mechanisms that coordinate the behavior of multiple cells in these processes is far from complete. Recent experiments with Madin-Darby canine kidney epithelial monolayers revealed a wave-like pattern of injury-induced MAPK activation and showed that it is essential for collective cell migration after wounding. To investigate the effects of the different aspects of wounding on cell sheet migration, we engineered a system that allowed us to dissect the classic wound healing assay. We studied Madin-Darby canine kidney sheet migration under three different conditions: 1) the classic wound healing assay, 2) empty space induction, where a confluent monolayer is grown adjacent to a slab of polydimethylsiloxane and the monolayer is not injured but allowed to migrate upon removal of the slab, and 3) injury via polydimethylsiloxane membrane peel-off, where an injured monolayer migrates onto plain tissue culture surface, as in the case of empty space induction allowing for direct comparison. By tracking the motion of individual cells within the sheet under these three conditions, we show how the dynamics of the individual cells' motion is responsible for the coordinated migration of the sheet and is coordinated with the activation of ERK1/2 MAPK. In addition, we demonstrate that the propagation of the waves of MAPK activation depends on the generation of reactive oxygen species at the wound edge.\",\n \"title\": \"Role of boundary conditions in an experimental model of epithelial wound healing.\"\n },\n {\n \"docid\": \"26283293\",\n \"text\": \"Eukaryotic cells are compartmentalized into membrane-bounded organelles whose functions rely on lipid trafficking to achieve membrane-specific compositions of lipids. Here we focused on the Ups1-Mdm35 system, which mediates phosphatidic acid (PA) transfer between the outer and inner mitochondrial membranes, and determined the X-ray structures of Mdm35 and Ups1-Mdm35 with and without PA. The Ups1-Mdm35 complex constitutes a single domain that has a deep pocket and flexible Ω-loop lid. Structure-based mutational analyses revealed that a basic residue at the pocket bottom and the Ω-loop lid are important for PA extraction from the membrane following Ups1 binding. Ups1 binding to the membrane is enhanced by the dissociation of Mdm35. We also show that basic residues around the pocket entrance are important for Ups1 binding to the membrane and PA extraction. These results provide a structural basis for understanding the mechanism of PA transfer between mitochondrial membranes.\",\n \"title\": \"Structural and mechanistic insights into phospholipid transfer by Ups1–Mdm35 in mitochondria\"\n },\n {\n \"docid\": \"8247597\",\n \"text\": \"Mutations and deletions in the mitochondrial genome (mtDNA), as well as instability of the nuclear genome, are involved in multiple human diseases. Here, we report that in Saccharomyces cerevisiae, loss of mtDNA leads to nuclear genome instability, through a process of cell-cycle arrest and selection we define as a cellular crisis. This crisis is not mediated by the absence of respiration, but instead correlates with a reduction in the mitochondrial membrane potential. Analysis of cells undergoing this crisis identified a defect in iron-sulfur cluster (ISC) biogenesis, which requires normal mitochondrial function. We found that downregulation of nonmitochondrial ISC protein biogenesis was sufficient to cause increased genomic instability in cells with intact mitochondrial function. These results suggest mitochondrial dysfunction stimulates nuclear genome instability by inhibiting the production of ISC-containing protein(s), which are required for maintenance of nuclear genome integrity. For a video summary of this article, see the PaperFlick file available with the online Supplemental Data.\",\n \"title\": \"Mitochondrial Dysfunction Leads to Nuclear Genome Instability via an Iron-Sulfur Cluster Defect\"\n },\n {\n \"docid\": \"4447055\",\n \"text\": \"Contusive spinal cord injury leads to a variety of disabilities owing to limited neuronal regeneration and functional plasticity. It is well established that an upregulation of glial-derived chondroitin sulphate proteoglycans (CSPGs) within the glial scar and perineuronal net creates a barrier to axonal regrowth and sprouting. Protein tyrosine phosphatase σ (PTPσ), along with its sister phosphatase leukocyte common antigen-related (LAR) and the nogo receptors 1 and 3 (NgR), have recently been identified as receptors for the inhibitory glycosylated side chains of CSPGs. Here we find in rats that PTPσ has a critical role in converting growth cones into a dystrophic state by tightly stabilizing them within CSPG-rich substrates. We generated a membrane-permeable peptide mimetic of the PTPσ wedge domain that binds to PTPσ and relieves CSPG-mediated inhibition. Systemic delivery of this peptide over weeks restored substantial serotonergic innervation to the spinal cord below the level of injury and facilitated functional recovery of both locomotor and urinary systems. Our results add a new layer of understanding to the critical role of PTPσ in mediating the growth-inhibited state of neurons due to CSPGs within the injured adult spinal cord.\",\n \"title\": \"Modulation of the proteoglycan receptor PTPσ promotes recovery after spinal cord injury\"\n }\n]"}}},{"rowIdx":198,"cells":{"query_id":{"kind":"string","value":"7927"},"query":{"kind":"string","value":"What does the -V indicate on MKC ticker"},"positive_passages":{"kind":"list like","value":[{"docid":"573958","text":"MKC is non-voting stock, MKC/V is voting stock. Ofter times you'll see two or more stock symbols for a company. These usually reflect different classes of stocks. For example, voting vs. non-voting (as in this case) or preferred vs non-preferred stock.","title":""}],"string":"[\n {\n \"docid\": \"573958\",\n \"text\": \"MKC is non-voting stock, MKC/V is voting stock. Ofter times you'll see two or more stock symbols for a company. These usually reflect different classes of stocks. For example, voting vs. non-voting (as in this case) or preferred vs non-preferred stock.\",\n \"title\": \"\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"193050","text":"TIAA-Cref has their Social Choice Equity Fund, which is a Large Blend primarily equity fund that invests given the following consideration: The Fund primarily invests in companies that are screened by MSCI Inc. (“MSCI”) to favor companies that meet or exceed certain environmental, social and governance (“ESG”) criteria. The Fund does this by investing in U.S. companies included in one or more MSCI ESG Indices that meet or exceed the screening criteria described below. Prior to being eligible for inclusion in the MSCI ESG Indices, companies are subject to an ESG performance evaluation conducted by MSCI, consisting of numerous factors. The ESG evaluation process favors companies that are: (i) strong stewards of the environment; (ii) devoted to serving local communities where they operate and to human rights and philanthropy; (iii) committed to higher labor standards for their own employees and those in the supply chain; (iv) dedicated to producing high-quality and safe products; and (v) managed in an exemplary and ethical manner. https://www.tiaa.org/public/offer/products/mutual-funds/responsible-investing","title":""},{"docid":"517161","text":"\"Considering the fact that you are so unaware of how to find such data, I find it very very hard to believe that you actually need it. \"\"All trade and finance data for as much tickers and markets as possible.\"\" Wtf does that even mean. You could be referencing thousands of different types of data for any given \"\"ticker\"\" with a statement so vague. What are you looking for?\"","title":""},{"docid":"11184","text":"\"The Dividend Discount Model is based on the concept that the present value of a stock is the sum of all future dividends, discounted back to the present. Since you said: dividends are expected to grow at a constant rate in perpetuity ... the Gordon Growth Model is a simple variant of the DDM, tailored for a firm in \"\"steady state\"\" mode, with dividends growing at a rate that can be sustained forever. Consider McCormick (MKC), who's last dividend was 31 cents, or $1.24 annualized. The dividend has been growing just a little over 7% annually. Let's use a discount, or hurdle rate of 10%. MKC closed today at $50.32, for what it's worth. The model is extremely sensitive to inputs. As g approaches r, the stock price rises to infinity. If g > r, stock goes negative. Be conservative with 'g' -- it must be sustainable forever. The next step up in complexity is the two-stage DDM, where the company is expected to grow at a higher, unsustainable rate in the early years (stage 1), and then settling down to the terminal rate for stage 2. Stage 1 is the present value of dividends during the high growth period. Stage 2 is the Gordon Model, starting at the end of stage 1, and discounting back to the present. Consider Abbott Labs (ABT). The current annual dividend is $1.92, the current dividend growth rate is 12%, and let's say that continues for ten years (n), after which point the growth rate is 5% in perpetuity. Again, the discount rate is 10%. Stage 1 is calculated as follows: Stage 2 is GGM, using not today's dividend, but the 11th year's dividend, since stage 1 covered the first ten years. 'gn' is the terminal growth, 5% in our case. then... The value of the stock today is 21.22 + 51.50 = 72.72 ABT closed today at $56.72, for what it's worth.\"","title":""},{"docid":"583941","text":"\"Answering this question is weird, because it is not really precise in what you mean. Do you want all stocks in the US? Do you want a selection of stocks according to parameters? Do you just want a cool looking graph? However, your possible misuse of the word derivative piqued my interest. Your reference to gold and silver seems to indicate that you do not know what a derivative actually is. Or what it would do in a portfolio. The straightforward way to \"\"see\"\" an efficient frontier is to do the following. For a set of stocks (in this case six \"\"randomly\"\" selected ones): library(quantmod) library(fPortfolio) library(PerformanceAnalytics) getSymbols(c(\"\"STZ\"\", \"\"RAI\"\", \"\"AMZN\"\", \"\"MSFT\"\", \"\"TWX\"\", \"\"RHT\"\"), from = \"\"2012-06-01\"\", to = \"\"2017-06-01\"\") returns <- NULL tickerlist <- c(\"\"STZ\"\", \"\"RAI\"\", \"\"AMZN\"\", \"\"MSFT\"\", \"\"TWX\"\", \"\"RHT\"\") for (ticker in tickerlist){ returns <- cbind(returns, monthlyReturn(Ad(eval(as.symbol(ticker))))) } colnames(returns) <- tickerlist returns <- as.timeSeries(returns) frontier <- portfolioFrontier(returns) png(\"\"frontier.png\"\", width = 800, height = 600) plot(frontier, which = \"\"all\"\") dev.off() minvariancePortfolio(returns, constraints = \"\"LongOnly\"\") Portfolio Weights: STZ RAI AMZN MSFT TWX RHT 0.1140 0.3912 0.0000 0.1421 0.1476 0.2051 Covariance Risk Budgets: STZ RAI AMZN MSFT TWX RHT 0.1140 0.3912 0.0000 0.1421 0.1476 0.2051 Target Returns and Risks: mean Cov CVaR VaR 0.0232 0.0354 0.0455 0.0360 https://imgur.com/QIxDdEI The minimum variance portfolio of these six assets has a mean return is 0.0232 and variance is 0.0360. AMZN does not get any weight in the portfolio. It kind of means that the other assets span it and it does not provide any additional diversification benefit. Let us add two ETFs that track gold and silver to the mix, and see how little difference it makes: getSymbols(c(\"\"GLD\"\", \"\"SLV\"\"), from = \"\"2012-06-01\"\", to = \"\"2017-06-01\"\") returns <- NULL tickerlist <- c(\"\"STZ\"\", \"\"RAI\"\", \"\"AMZN\"\", \"\"MSFT\"\", \"\"TWX\"\", \"\"RHT\"\", \"\"GLD\"\", \"\"SLV\"\") for (ticker in tickerlist){ returns <- cbind(returns, monthlyReturn(Ad(eval(as.symbol(ticker))))) } colnames(returns) <- tickerlist returns <- as.timeSeries(returns) frontier <- portfolioFrontier(returns) png(\"\"weights.png\"\", width = 800, height = 600) weightsPlot(frontier) dev.off() # Optimal weights out <- minvariancePortfolio(returns, constraints = \"\"LongOnly\"\") wghts <- getWeights(out) portret1 <- returns%*%wghts portret1 <- cbind(monthprc, portret1)[,3] colnames(portret1) <- \"\"Optimal portfolio\"\" # Equal weights wghts <- rep(1/8, 8) portret2 <- returns%*%wghts portret2 <- cbind(monthprc, portret2)[,3] colnames(portret2) <- \"\"Equal weights portfolio\"\" png(\"\"performance_both.png\"\", width = 800, height = 600) par(mfrow=c(2,2)) chart.CumReturns(portret1, ylim = c(0, 2)) chart.CumReturns(portret2, ylim = c(0, 2)) chart.Drawdown(portret1, main = \"\"Drawdown\"\", ylim = c(-0.06, 0)) chart.Drawdown(portret2, main = \"\"Drawdown\"\", ylim = c(-0.06, 0)) dev.off() https://imgur.com/sBHGz7s Adding gold changes the minimum variance mean return to 0.0116 and the variance stays about the same 0.0332. You can see how the weights change at different return and variance profiles in the picture. The takeaway is that adding gold decreases the return but does not do a lot for the risk of the portfolio. You also notice that silver does not get included in the minimum variance efficient portfolio (and neither does AMZN). https://imgur.com/rXPbXau We can also compare the optimal weights to an equally weighted portfolio and see that the latter would have performed better but had much larger drawdowns. Which is because it has a higher volatility, which might be undesirable. --- Everything below here is false, but illustrative. So what about the derivative part? Let us assume you bought an out of the money call option with a strike of 50 on MSFT at the beginning of the time series and held it to the end. We need to decide on the the annualized cost-of-carry rate, the annualized rate of interest, the time to maturity is measured in years, the annualized volatility of the underlying security is proxied by the historical volatility. library(fOptions) monthprc <- Ad(MSFT)[endpoints(MSFT, \"\"months\"\")] T <- length(monthprc) # 60 months, 5 years vol <- sd(returns$MSFT)*sqrt(12) # annualized volatility optprc <- matrix(NA, 60, 1) for (t in 1:60) { s <- as.numeric(monthprc[t]) optval <- GBSOption(TypeFlag = \"\"c\"\", S = s, X = 50, Time = (T - t) / 12, r = 0.001, b = 0.001, sigma = vol) optprc[t] <- optval@price } monthprc <- cbind(monthprc, optprc) colnames(monthprc) <- c(\"\"MSFT\"\", \"\"MSFTCall50\"\") MSFTCall50rets <- monthlyReturn(monthprc[,2]) colnames(MSFTCall50rets) <- \"\"MSFTCall50rets\"\" returns <- merge(returns, MSFTCall50rets) wghts <- rep(1/9, 9) portret3 <- returns%*%wghts portret3 <- cbind(monthprc, portret3)[,3] colnames(portret3) <- \"\"Equal weights derivative portfolio\"\" png(\"\"performance_deriv.png\"\", width = 800, height = 600) par(mfrow=c(2,2)) chart.CumReturns(portret2, ylim = c(0, 4.5)) chart.CumReturns(portret3, ylim = c(0, 4.5)) chart.Drawdown(portret2, main = \"\"Drawdown\"\", ylim = c(-0.09, 0)) chart.Drawdown(portret3, main = \"\"Drawdown\"\", ylim = c(-0.09, 0)) dev.off() https://imgur.com/SZ1xrYx Even though we have a massively profitable instrument in the derivative. The portfolio analysis does not include it because of the high volatility. However, if we just use equal weighting and essentially take a massive position in the out of the money call (which would not be possible in real life), we get huge drawdowns and volatility, but the returns are almost two fold. But nobody will sell you a five year call. Others can correct any mistakes or misunderstandings in the above. It hopefully gives a starting point. Read more at: https://en.wikipedia.org/wiki/Modern_portfolio_theory https://en.wikipedia.org/wiki/Option_(finance) The imgur album: https://imgur.com/a/LoBEY\"","title":""},{"docid":"472663","text":"\"An Exchange-Traded Fund (ETF) is a special type of mutual fund that is traded on the stock exchange like a stock. To invest, you buy it through a stock broker, just as you would if you were buying an individual stock. When looking at a mutual fund based in the U.S., the easiest way to tell whether or not it is an ETF is by looking at the ticker symbol. Traditional mutual funds have ticker symbols that end in \"\"X\"\", and ETFs have ticker symbols that do not end in \"\"X\"\". The JPMorgan Emerging Markets Equity Fund, with ticker symbol JFAMX, is a traditional mutual fund, not an ETF. JPMorgan does have ETFs; the JPMorgan Diversified Return Emerging Markets Equity ETF, with ticker symbol JPEM, is an example. This ETF invests in similar stocks as JFAMX; however, because it is an index-based fund instead of an actively managed fund, it has lower fees. If you aren't sure about the ticker symbol, the advertising/prospectus of any ETF should clearly state that it is an ETF. (In the example of JPEM above, they put \"\"ETF\"\" right in the fund name.) If you don't see ETF mentioned, it is most likely a traditional mutual fund. Another way to tell is by looking at the \"\"investment minimums\"\" of the fund. JFAMX has a minimum initial investment of $1000. ETFs, however, do not have an investment minimum listed; because it is traded like a stock, you simply buy whole shares at whatever the current share price is. So if you look at the \"\"Fees and Investment Minimums\"\" section of the JPEM page, you'll see the fees listed, but not any investment minimums.\"","title":""},{"docid":"350191","text":"\"Things are in fact more complicated. It really depends what you mean by \"\"ticker\"\" and who gave you this ticker. There is several codes to identify a security: The Bloomberg code contains a code to identify the exchange as in ALU:FP the FP part refers to Euronext Paris. The RIC code works the same way but with a different convention. Exchanges are identified by the MIC code.(they are in fact divided in market segments with each market segment having a main market segment) ISIN and SEDOL codes do not provide informations about the exchange so they are usually given with a MIC. There is no guarantee that Reuters and Bloomberg won't use the same company code to refer to different company. But they usually use the exchange ticker. This ticker is requested by each company and can be anything. They are accepted most of the time. But sometimes to avoid confusion some requests are rejected. (For instance FBI ticker was refused) For more info read: The evolution of ticker symbols Financial providers like Bloomberg provides services to be informed when a security is added/removed from a market.\"","title":""},{"docid":"195089","text":"Willis Group Holdings Set to Join the S&P 500; Fossil Group to Join S&P MidCap 400; Adeptus Health to Join S&P SmallCap 600 notes in part for the S & P case: Willis Group Holdings plc (NYSE:WSH) will replace Fossil Group Inc. (NASD:FOSL) in the S&P 500, and Fossil Group will replace Towers Watson & Co. (NASD:TW) in the S&P MidCap 400 after the close of trading on Monday, January 4. Willis Group is merging with Towers Watson in a deal expected to be completed on or about that date pending final conditions. Post merger, Willis Group Holdings will change its name to Willis Towers Watson plc and trade under the ticker symbol “WLTW”. Fossil has a market capitalization that is more representative of the midcap market space. As of Jan. 8, Fossil is about $1.44B in market cap and Willis is $21.02B for those wondering. Apple with a market cap of $540.58B is 3.26% of the index making the entire index worth approximately $16,582.21B, so Fossil is worth .00868% of the overall index for those wanting some numbers here. Thus, if a company acquires another and becomes bigger than there can be replacements made in those indices that have an artificial number of small members. Alternatively, a member may be removed for lack of representation where it is just so small compared to other companies that may be a better fit as some indices could be viewed as actively managed in a sense. In contrast, there are indices like those from Russell, known for the Russell 2000 small-cap index: Q: Why don't you reconstitute the indexes more often than once a year? A: Maintaining representative indexes must be weighed against the costs associated with making frequent changes to index constituents (namely, buying and selling stocks). The Russell Indexes are annually reconstituted because our research has shown that this strikes a reasonable balance between accuracy and cost. We originally reconstituted our indexes quarterly, then semi-annually, but found these options to be suboptimal. Our extensive research demonstrates that annual reconstitution accurately represents the capitalization segments and minimizes the turnover required to reflect the segments as they change. Thus there can be different scenarios. Then there can be the effect on index funds when price-weighted indices like the Dow Jones Industrial Average has a member that does a stock split that causes some rebalancing too. On the DJIA Divisor: The Dow Jones Industrial Average (DJIA) is a price-weighted index that is calculated by dividing the sum of the prices of the 30 component stocks (Dow Jones Industrial Average components) by a number called the DJIA Divisor or Dow Divisor . The index divisor is updated periodically and adjusted to offset the effect of stock splits, bonus issues or any change in the component stocks included in the DJIA. This is done in order to keep the index value consistent.","title":""},{"docid":"341293","text":"\"When they entered Bankruptcy they changed their stock symbol from AAMR to AAMRQ. The Q tells investors that the company i in Bankruptcy. This i what the SEC says about the Q: \"\"Q\"\" Added To Stock Ticker Symbol When a company is involved in bankruptcy proceedings, the letter \"\"Q\"\" is added to the end of the company's stock ticker symbol. In most cases, when a company emerges from bankruptcy, the reorganization plan will cancel the existing equity stock and the old shares will be worthless. Given that risk, before purchasing stock in a bankrupt company, investors should read the company's proposed plan of reorganization. For more information about the impact of bankruptcy proceedings on securities, please read our online publication, Corporate Bankruptcy. The risks are they never recover, or that the old shares have nothing to do with new company. Many investors don't understand this. Recently some uninformed investors(?) tried to get a jump on the Twitter IPO by purchasing share of what they thought was Twitter but was instead the bankrupt company Tweeter Home Entertainment. Shares of Tweeter Home Entertainment, a Boston-based consumer electronics chain that filed for bankruptcy in 2007, soared Friday in a case of mistaken identity on Wall Street. Apparently, some investors confused Tweeter, which trades under the symbol TWTRQ, with Twitter and piled into the penny stock. Tweeter, which trades over the counter, opened at 2 cents a share and jumped as much as 15 cents — or 1,800 percent — before regulators halted trading. Almost 15 million shares had changed hands at that point, while the average daily volume is closer to 150,000. Sometimes it does happen that the new company does give some value to the old investors, but more often then not the old investors are completely wiped out.\"","title":""},{"docid":"3118","text":"Dividends are normally paid in cash, so don't generally affect your portfolio aside from a slight increase to 'cash'. You get a check for them, or your broker would deposit the funds into a money-market account for you. There is sometimes an option to re-invest dividends, See Westyfresh's answer regarding Dividend Re-Investment Plans. As Tom Au described, the dividends are set by the board of directors and announced. Also as he indicated just before the 'record' date, a stock which pays dividends is worth slightly more (reflecting the value of the dividend that will be paid to anyone holding the stock on the record date) and goes down by the dividend amount immediately after that date (since you'd now have to hold the stock till the next record date to get a dividend) In general unless there's a big change in the landscape (such as in late 2008) most companies pay out about the same dividend each time, and changes to this are sometimes seen by some as 'indicators' of company health and such news can result in movement in the stock price. When you look at a basic quote on a ticker symbol there is usually a line for Div/yeild which gives the amount of dividend paid per share, and the relative yeild (as a percentage of the stock price). If a company has been paying dividends, this field will have values in it, if a company does not pay a dividend it will be blank or say NA (depending on where you get the quote). This is the easiest way to see if a company pays a dividend or not. for example if you look at this quote for Google, you can see it pays no dividend Now, in terms of telling when and how much of a dividend has been paid, most financial sites have the option when viewing a stock chart to show the dividend payments. If you expand the chart to show at least a year, you can see when and how much was paid in terms of dividends. For example you can see from this chart that MSFT pays dividends once a quarter, and used to pay out 13 cents, but recently changed to 16 cents. if you were to float your mouse over one of those icons it would also give the date the dividend was paid.","title":""},{"docid":"397445","text":"\"That share class may not have a ticker symbol though \"\"Black Rock MSCI ACWI ex-US Index\"\" does have a ticker for \"\"Investor A\"\" shares that is BDOAX. Some funds will have multiple share classes that is a way to have fees be applied in various ways. Mutual fund classes would be the SEC document about this if you want a government source within the US around this. Something else to consider is that if you are investing in a \"\"Fund of funds\"\" is that there can be two layers of expense ratios to consider. Vanguard is well-known for keeping its expenses low.\"","title":""},{"docid":"369424","text":"\"The official source is the most recent Form 13F that Berkshire Hathaway, which is filed with the Securities & Exchange Commission on a quarterly basis . You can find it through the SEC filing search engine, using BRKA as the ticker symbol. and then looking for the filings marked 13-FR or 13-FR/A (the \"\"/A\"\" indicates an amended filing). As you can see by looking at the 13-F filed for the quarter ending September 30 , the document isn't pretty or necessarily easy to read, hence the popularity of sites such as those that Chad linked to. It is, though, the truly official source from which websites tracking the Berkshire Hathaway portfolio derive their information.\"","title":""},{"docid":"323133","text":"\"I said the majority, not ALL. (And the vast majority of people -- again even within the \"\"sciences\"\" -- are in fact mediocrities). That doesn't mean it take some \"\"super-genius\"\" to see past the fraud, but it does take a sharp mind, AND it then takes an interest and time to look into the evidence (what little there actually is). Many people within the hard sciences are more than capable of seeing through the fraud and foolishness of psychology/psychiatry. Indeed, many *have* done so. (Cf [Feynman](http://www.rationalskepticism.org/psychology/richard-feynman-briefly-on-psychology-t967.html), and of course the aforementioned [John Ioannidis](psychcentral.com/blog/archives/2010/10/19/what-research-can-you-believe/) who has debunked a LOT of so called \"\"research\"\" in both psychiatry and other medical \"\"science\"\" research). But far more often those with sharp minds are busy with a lot of other endeavors, and so long as they have no driving need, they do not really examine other fields to much dept (in most cases they do not investigate other fields at all). What is more is that psychologists & [psychiatrists themselves know](http://www.youtube.com/watch?v=-P6_FwpVo_s) (and [when put on the spot will admit that there is no real science behind the malarkey](http://www.youtube.com/watch?v=atsCp2SErog) or the drugs) that they sell -- not that they really care of course.\"","title":""},{"docid":"265404","text":"What I ended up doing was finding where each ticker of Novo was registered (what exchange), then individually looking up the foreign taxation rules of the containing country. Luckily, most companies only have a few tickers so this wasn't too hard in the end.","title":""},{"docid":"27303","text":"Options - yes we can :) Options tickers on Yahoo! Finance will be displayed as per new options symbology announced by OCC. The basic parts of new option symbol are: Root symbol + Expiration Year(yy)+ Expiration Month(mm)+ Expiration Day(dd) + Call/Put Indicator (C or P) + Strike price Ex.: AAPL January 19 2013, Put 615 would be AAPL130119P00615000 http://finance.yahoo.com/q?s=AAPL130119P00615000&ql=1 Futures - yes as well (: Ex.: 6A.M12.E would be 6AM12.CME using Yahoo Finance symbology. (simple as that, try it out) Get your major futures symbols from here: http://quotes.ino.com/exchanges/exchange.html?e=CME","title":""},{"docid":"165973","text":"It depends on what site you're looking on and what exchange they're pulling the data from. Even though funds and stocks are called the same thing, they have different ticker symbols in each country's exchange or could be traded as pink sheet stocks in the US. If a company or fund is based in another country (like Canada or the UK) they probably also trade on that country's exchange (Toronto or London) under a different symbol. This can cause a lot of confusion when researching these tickers.","title":""},{"docid":"278113","text":"Reading this made me think of [this](https://www.youtube.com/watch?v=-s1s5K52zEQ). I wish you luck if you consider yourself an authority on a subject you have practically no exposure to, but hey, what does a hiring manager know? I mean, you're about to start an internship, so obviously everyone should want to know your opinion on the future of the market.","title":""},{"docid":"97075","text":"Steve Keen says otherwise, he says Banks CAN create a Quadrillion dollars, as long as there are willing borrowers. : http://www.youtube.com/watch?v=zc_fpGfyqGE. http://www.youtube.com/watch?v=4sSfPkIUHPk&feature=share why does m2 seem like exponential? how can fractional reserve do something like that? unpossible. seems like only an explosive growth in either productivity or profits through slave labor globalization or speculative derivatives can do something like that.","title":""},{"docid":"47276","text":"Presumably you mean to ask what happens if State Street files chapter 7 bankruptcy, since not all bankruptcy proceedings end in liquidation. SPY is a well known ticker, I can't imagine that there wouldn't be an eager bank willing to pay to pick up that ticker and immediately acquire all the assets related to it. The most likely scenario is that another bank would assume control of the ticker and assets, and the shares would continue trading as they always have. A less likely scenario is that no other financial institution wanted to acquire SPY, and the shares would be liquidated and the proceeds would go to the owners of shares of the ETF. Since the underlying assets are in companies that have actual value, the shares shouldn't trade at much of a discount prior to liquidation. Additionally, if there is a black swan event, there will probably be losses on the underlying assets, so it might even be helpful if the SPY fund was tied up in legal proceedings while everyone gets their heads straight in the market.","title":""},{"docid":"318774","text":"NYSE started allowing four letter tickers around 2009. NASDAQ allows 4-5 letter tickers. I guess they'll keep increasing when / if needed. Companies are allowed to change tickers, although there are costs. Tickers in the US are assigned through a single entity. Companies that are new need to take something that's open. http://www.wsj.com/articles/SB124296050986346159 I see that you're in Australia, but, since there aren't really that many options to deal with the problem that you mentioned, I'd guess that you'll ultimately do the same. Not sure about how tickers are assigned there though.","title":""},{"docid":"339268","text":"\"You cannot determine this solely by the ticker length. However, there are some conventions that may help steer you there. Nasdaq has 2-4 base letters BATS has 4 base letters NYSE equity securities have 1-4 base letters. NYSE Mkt (formerly Amex) have 1-4 base letters. NYSE Arca has 4 base letters OTC has 4 base letters. Security types other than equities may have additional letters added, and each exchange (and data vendors) have different conventions for how this is handled. So if you see \"\"T\"\" for a US-listed security it would be only be either NASDAQ, NYSE or NYSE Mkt. If you see \"\"ANET\"\" then you cannot tell which exchange it is listed on. (In this case, ANET Arista Networks is actually a NYSE stock). For some non-equity security types, such as hybrids, and debt instruments, some exchanges add \"\"P\"\" to the end for \"\"preferreds\"\" (Nasdaq and OTC) and NYSE/NYSE Mkt have a variety of methods (including not adding anything) to the ticker. Examples include NYSE:TFG, NYSEMkt:IPB, Nasdaaq: AGNCP, Nasdaq:OXLCN. It all becomes rather confusing given the changes in conventions over the years. Essentially, you require data that provides you with ticker, listing location and security type. The exchanges allocate security tickers in conjunction with the SEC so there are no overlaps. eg. The same ticker cannot represent two different securities. However, tickers can be re-used. For example, the ticker AB has been used by the following companies:\"","title":""},{"docid":"37568","text":"SECTION | CONTENT :--|:-- Title | Bitcoin explained real easy. Raise Your Frequency S1.E1 Description | Bitcoin explained real easy so anyone can understand what it is and how it works.. You decide which system you prefer: current money system: https://www.youtube.com/watch?v=G9IH-XKQpOI current money system: https://www.youtube.com/watch?v=PhSIfVyvDdM current money system: https://www.youtube.com/watch?v=JuP2hH0Kpro current money system: https://www.youtube.com/watch?v=Bx5Sc3vWefE Bitcoin: https://medium.com/zapchain-magazine/the-10-best-videos-to-watch-to-learn-about-bitcoin-c34f98f2fed... Length | 0:26:48 **** ^(I am a bot, this is an auto-generated reply | )^[Info](https://www.reddit.com/u/video_descriptionbot) ^| ^[Feedback](https://www.reddit.com/message/compose/?to=video_descriptionbot&subject=Feedback) ^| ^(Reply STOP to opt out permanently)","title":""},{"docid":"94159","text":"\"I don't have anything definitive, but in general positions in a company are not affected materially by what is called a corporate action. \"\"Corp Actions\"\" can really be anything that affects the details of a stock. Common examples are a ticker change, or exchange change, IPO (ie a new ticker), doing a split, or merging with another ticker. All of these events do not change the total value of people's positions. If a stock splits, you might have more shares, but they are worth less per share. A merger is quite similar to a split. The old company's stock is converted two the new companies stock at some ratio (ie 10 shares become 1 share) and then converted 1-to-1 to the new symbol. Shorting a stock that splits is no different. You shorted 10 shares, but after the split those are now 100 shares, when you exit the position you have to deliver back 100 \"\"new\"\" shares, though dollar-for-dollar they are the same total value. I don't see why a merger would affect your short position. The only difference is you are now shorting a different company, so when you exit the position you'll have to deliver shares of the new company back to the brokerage where you \"\"borrowed\"\" the shares you shorted.\"","title":""},{"docid":"252039","text":"Do you want to know How to Buy Bitcoins or How to Make Money in Bitcoin Investments. First of all, you should know What is Bitcoin? and What is Cryptocurrency? Through our this https://www.youtube.com/watch?v=xDIRVGkeONY video link you will get all the information whatever you want to know about Bitcoins. https://www.youtube.com/watch?v=xDIRVGkeONY","title":""},{"docid":"172703","text":"No, some of Vanguard's funds are index funds like their Total Stock Market Index and 500 Index. In contrast, there are funds like Vanguard PRIMECAP and Vanguard Wellington that are actively managed. There are index funds in both open-end and exchange-traded formats. VTI is the ticker for Vanguard's Total Stock Market ETF while VTSMX is an open-end mutual fund format. VOO would be the S & P 500 ETF ticker while VFINX is one of the open-end mutual fund tickers, where VIIIX has a really low expense ratio but a pretty stiff minimum to my mind. As a general note, open-end mutual funds will generally have a 5 letter ticker ending in X while an ETF will generally be shorter at 3 or 4 letters in length.","title":""},{"docid":"323749","text":"\"There are a number of ways to measure such things and they are generally called \"\"sentiment indicators\"\". The ones that I have seen \"\"work\"\", in the sense that they show relatively high readings near market tops and relatively low readings near market bottoms. The problem is that there are no thresholds that work consistently. For example, at one market top a sentiment indicator may read 62. At the next market top that same indicator might read 55. So what threshold do you use next time? Maybe the top will come at 53, or maybe it will not come until 65. There was a time when I could have listed examples for you with the names of the indicators and what they signaled and when. But I gave up on such things years ago after seeing such wide variation. I have been at this a long time (30+ years), and I have not found anything that works as well as we would like at identifying a top in real time. The best I have found (although it does give false signals) is a drop in price coupled with a bearish divergence in breadth. The latter is described in \"\"Stan Weinstein's Secrets For Profiting in Bull and Bear Markets\"\". Market bottoms are a little less difficult to identify in real time. One thing I would suggest if you think that there is some way to get a significant edge in investing, is to look at the results of Mark Hulbert's monitoring of newsletters. Virtually all of them rise and fall with the market and almost none are able to beat buy and hold of the Wilshire 5000 over the long term.\"","title":""},{"docid":"222075","text":"Oh, God! I remember that thing. Could this be considered *peak bullshit product*? This stupid juicer is one of the best examples of why you shouldn't throw technology at something that isn't a problem. Did people have a problem obtaining juice?! Does WiFi solve that problem? To give a counter example, I reckon this: https://shapertools.com/ is one of the BEST technological solutions to a problem that I've seen in a long time, and could be the beginning of a whole range of smart tools. EDIT: people are doubting that is exists. People are using the early models. I first saw the device while watching this video. https://www.youtube.com/watch?v=lfmrvxB154w&feature=youtu.be&t=3m10s Long video of people using and discussing it: https://www.youtube.com/watch?v=p_wk3q8jWcs If you check YouTube, there are loads of videos. https://www.youtube.com/results?search_query=shaper+origin","title":""},{"docid":"475984","text":"\"Thanks for pointing out [the study](http://papers.ssrn.com/sol3/papers.cfm?abstract_id=1748851). It's a slightly different cause than what I was describing when I posted this. Specifically, they show an effect not when the names get confused, but rather when the name similarity simply brings more attention to the stock. I was surprised nobody mentioned that in response to my post. But also interesting is that they had to control for simple confusion between stock symbols, which implies that ticker confusion has a known effect. So I dug into research on that and quickly found [this study](http://www.efmaefm.org/0EFMAMEETINGS/EFMA%20ANNUAL%20MEETINGS/2010-Aarhus/EFMA2010_0161_fullpaper.pdf) found \"\"a high positive correlation between returns on two matching stocks with similar ticker symbols\"\".\"","title":""},{"docid":"550661","text":"Google will be issuing Class C shares (under the ticker symbol GOOCV) to current GOOG holders in the beginning of April. The Class C shares and Class A shares will then change symbols, with the Class C shares trading under GOOG. This was announced on January 30th. Details are in this benzinga article: Projected Trading Timeline March 27 - April 2 Record Date - Payment Date Class C shares commence trading on March 27 as GOOCV on a when issued basis Class A shares continue to trade as GOOG, with entitlement to Class C shares Class A shares will also trade on an ex-distribution basis, without entitlement to the Class C shares, as GOOAV April 3 EX Date The ticker for the Class A shares will change from GOOG to GOOGL The ticker for the Class C shares will change from GOOCV to GOOG and commence regular way trading The ticker for the Class A shares that traded on an ex-distribution basis - GOOAV - will be suspended","title":""},{"docid":"104901","text":"There's an interesting paper, Does Investor Attention Affect Stock Prices? (Sandhya et al), where researchers look at related stock tickers. When a large cap, better-known stock jumps, smaller firms with similar symbols also rise. Pretty nuts -- I interviewed the author of the paper [here](http://www.tradestreaming.com/?p=3745). There's also a transcript.","title":""},{"docid":"448938","text":"\"The 3-letter tickers are from a different era.... Nowadays the usage of tickers is more of a \"\"legacy\"\" tradition rather than a current necessity. As such they're no longer limited to 3 characters. And the characters don't have to be related to the actual name. For example a company named Alphabet is trading on NASDAQ under the ticker \"\"GOOGL\"\". It has 5 characters, not 3, and (almost) none of them appear in the name of the company (used to, but not anymore).\"","title":""}],"string":"[\n {\n \"docid\": \"193050\",\n \"text\": \"TIAA-Cref has their Social Choice Equity Fund, which is a Large Blend primarily equity fund that invests given the following consideration: The Fund primarily invests in companies that are screened by MSCI Inc. (“MSCI”) to favor companies that meet or exceed certain environmental, social and governance (“ESG”) criteria. The Fund does this by investing in U.S. companies included in one or more MSCI ESG Indices that meet or exceed the screening criteria described below. Prior to being eligible for inclusion in the MSCI ESG Indices, companies are subject to an ESG performance evaluation conducted by MSCI, consisting of numerous factors. The ESG evaluation process favors companies that are: (i) strong stewards of the environment; (ii) devoted to serving local communities where they operate and to human rights and philanthropy; (iii) committed to higher labor standards for their own employees and those in the supply chain; (iv) dedicated to producing high-quality and safe products; and (v) managed in an exemplary and ethical manner. https://www.tiaa.org/public/offer/products/mutual-funds/responsible-investing\",\n \"title\": \"\"\n },\n {\n \"docid\": \"517161\",\n \"text\": \"\\\"Considering the fact that you are so unaware of how to find such data, I find it very very hard to believe that you actually need it. \\\"\\\"All trade and finance data for as much tickers and markets as possible.\\\"\\\" Wtf does that even mean. You could be referencing thousands of different types of data for any given \\\"\\\"ticker\\\"\\\" with a statement so vague. What are you looking for?\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"11184\",\n \"text\": \"\\\"The Dividend Discount Model is based on the concept that the present value of a stock is the sum of all future dividends, discounted back to the present. Since you said: dividends are expected to grow at a constant rate in perpetuity ... the Gordon Growth Model is a simple variant of the DDM, tailored for a firm in \\\"\\\"steady state\\\"\\\" mode, with dividends growing at a rate that can be sustained forever. Consider McCormick (MKC), who's last dividend was 31 cents, or $1.24 annualized. The dividend has been growing just a little over 7% annually. Let's use a discount, or hurdle rate of 10%. MKC closed today at $50.32, for what it's worth. The model is extremely sensitive to inputs. As g approaches r, the stock price rises to infinity. If g > r, stock goes negative. Be conservative with 'g' -- it must be sustainable forever. The next step up in complexity is the two-stage DDM, where the company is expected to grow at a higher, unsustainable rate in the early years (stage 1), and then settling down to the terminal rate for stage 2. Stage 1 is the present value of dividends during the high growth period. Stage 2 is the Gordon Model, starting at the end of stage 1, and discounting back to the present. Consider Abbott Labs (ABT). The current annual dividend is $1.92, the current dividend growth rate is 12%, and let's say that continues for ten years (n), after which point the growth rate is 5% in perpetuity. Again, the discount rate is 10%. Stage 1 is calculated as follows: Stage 2 is GGM, using not today's dividend, but the 11th year's dividend, since stage 1 covered the first ten years. 'gn' is the terminal growth, 5% in our case. then... The value of the stock today is 21.22 + 51.50 = 72.72 ABT closed today at $56.72, for what it's worth.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"583941\",\n \"text\": \"\\\"Answering this question is weird, because it is not really precise in what you mean. Do you want all stocks in the US? Do you want a selection of stocks according to parameters? Do you just want a cool looking graph? However, your possible misuse of the word derivative piqued my interest. Your reference to gold and silver seems to indicate that you do not know what a derivative actually is. Or what it would do in a portfolio. The straightforward way to \\\"\\\"see\\\"\\\" an efficient frontier is to do the following. For a set of stocks (in this case six \\\"\\\"randomly\\\"\\\" selected ones): library(quantmod) library(fPortfolio) library(PerformanceAnalytics) getSymbols(c(\\\"\\\"STZ\\\"\\\", \\\"\\\"RAI\\\"\\\", \\\"\\\"AMZN\\\"\\\", \\\"\\\"MSFT\\\"\\\", \\\"\\\"TWX\\\"\\\", \\\"\\\"RHT\\\"\\\"), from = \\\"\\\"2012-06-01\\\"\\\", to = \\\"\\\"2017-06-01\\\"\\\") returns <- NULL tickerlist <- c(\\\"\\\"STZ\\\"\\\", \\\"\\\"RAI\\\"\\\", \\\"\\\"AMZN\\\"\\\", \\\"\\\"MSFT\\\"\\\", \\\"\\\"TWX\\\"\\\", \\\"\\\"RHT\\\"\\\") for (ticker in tickerlist){ returns <- cbind(returns, monthlyReturn(Ad(eval(as.symbol(ticker))))) } colnames(returns) <- tickerlist returns <- as.timeSeries(returns) frontier <- portfolioFrontier(returns) png(\\\"\\\"frontier.png\\\"\\\", width = 800, height = 600) plot(frontier, which = \\\"\\\"all\\\"\\\") dev.off() minvariancePortfolio(returns, constraints = \\\"\\\"LongOnly\\\"\\\") Portfolio Weights: STZ RAI AMZN MSFT TWX RHT 0.1140 0.3912 0.0000 0.1421 0.1476 0.2051 Covariance Risk Budgets: STZ RAI AMZN MSFT TWX RHT 0.1140 0.3912 0.0000 0.1421 0.1476 0.2051 Target Returns and Risks: mean Cov CVaR VaR 0.0232 0.0354 0.0455 0.0360 https://imgur.com/QIxDdEI The minimum variance portfolio of these six assets has a mean return is 0.0232 and variance is 0.0360. AMZN does not get any weight in the portfolio. It kind of means that the other assets span it and it does not provide any additional diversification benefit. Let us add two ETFs that track gold and silver to the mix, and see how little difference it makes: getSymbols(c(\\\"\\\"GLD\\\"\\\", \\\"\\\"SLV\\\"\\\"), from = \\\"\\\"2012-06-01\\\"\\\", to = \\\"\\\"2017-06-01\\\"\\\") returns <- NULL tickerlist <- c(\\\"\\\"STZ\\\"\\\", \\\"\\\"RAI\\\"\\\", \\\"\\\"AMZN\\\"\\\", \\\"\\\"MSFT\\\"\\\", \\\"\\\"TWX\\\"\\\", \\\"\\\"RHT\\\"\\\", \\\"\\\"GLD\\\"\\\", \\\"\\\"SLV\\\"\\\") for (ticker in tickerlist){ returns <- cbind(returns, monthlyReturn(Ad(eval(as.symbol(ticker))))) } colnames(returns) <- tickerlist returns <- as.timeSeries(returns) frontier <- portfolioFrontier(returns) png(\\\"\\\"weights.png\\\"\\\", width = 800, height = 600) weightsPlot(frontier) dev.off() # Optimal weights out <- minvariancePortfolio(returns, constraints = \\\"\\\"LongOnly\\\"\\\") wghts <- getWeights(out) portret1 <- returns%*%wghts portret1 <- cbind(monthprc, portret1)[,3] colnames(portret1) <- \\\"\\\"Optimal portfolio\\\"\\\" # Equal weights wghts <- rep(1/8, 8) portret2 <- returns%*%wghts portret2 <- cbind(monthprc, portret2)[,3] colnames(portret2) <- \\\"\\\"Equal weights portfolio\\\"\\\" png(\\\"\\\"performance_both.png\\\"\\\", width = 800, height = 600) par(mfrow=c(2,2)) chart.CumReturns(portret1, ylim = c(0, 2)) chart.CumReturns(portret2, ylim = c(0, 2)) chart.Drawdown(portret1, main = \\\"\\\"Drawdown\\\"\\\", ylim = c(-0.06, 0)) chart.Drawdown(portret2, main = \\\"\\\"Drawdown\\\"\\\", ylim = c(-0.06, 0)) dev.off() https://imgur.com/sBHGz7s Adding gold changes the minimum variance mean return to 0.0116 and the variance stays about the same 0.0332. You can see how the weights change at different return and variance profiles in the picture. The takeaway is that adding gold decreases the return but does not do a lot for the risk of the portfolio. You also notice that silver does not get included in the minimum variance efficient portfolio (and neither does AMZN). https://imgur.com/rXPbXau We can also compare the optimal weights to an equally weighted portfolio and see that the latter would have performed better but had much larger drawdowns. Which is because it has a higher volatility, which might be undesirable. --- Everything below here is false, but illustrative. So what about the derivative part? Let us assume you bought an out of the money call option with a strike of 50 on MSFT at the beginning of the time series and held it to the end. We need to decide on the the annualized cost-of-carry rate, the annualized rate of interest, the time to maturity is measured in years, the annualized volatility of the underlying security is proxied by the historical volatility. library(fOptions) monthprc <- Ad(MSFT)[endpoints(MSFT, \\\"\\\"months\\\"\\\")] T <- length(monthprc) # 60 months, 5 years vol <- sd(returns$MSFT)*sqrt(12) # annualized volatility optprc <- matrix(NA, 60, 1) for (t in 1:60) { s <- as.numeric(monthprc[t]) optval <- GBSOption(TypeFlag = \\\"\\\"c\\\"\\\", S = s, X = 50, Time = (T - t) / 12, r = 0.001, b = 0.001, sigma = vol) optprc[t] <- optval@price } monthprc <- cbind(monthprc, optprc) colnames(monthprc) <- c(\\\"\\\"MSFT\\\"\\\", \\\"\\\"MSFTCall50\\\"\\\") MSFTCall50rets <- monthlyReturn(monthprc[,2]) colnames(MSFTCall50rets) <- \\\"\\\"MSFTCall50rets\\\"\\\" returns <- merge(returns, MSFTCall50rets) wghts <- rep(1/9, 9) portret3 <- returns%*%wghts portret3 <- cbind(monthprc, portret3)[,3] colnames(portret3) <- \\\"\\\"Equal weights derivative portfolio\\\"\\\" png(\\\"\\\"performance_deriv.png\\\"\\\", width = 800, height = 600) par(mfrow=c(2,2)) chart.CumReturns(portret2, ylim = c(0, 4.5)) chart.CumReturns(portret3, ylim = c(0, 4.5)) chart.Drawdown(portret2, main = \\\"\\\"Drawdown\\\"\\\", ylim = c(-0.09, 0)) chart.Drawdown(portret3, main = \\\"\\\"Drawdown\\\"\\\", ylim = c(-0.09, 0)) dev.off() https://imgur.com/SZ1xrYx Even though we have a massively profitable instrument in the derivative. The portfolio analysis does not include it because of the high volatility. However, if we just use equal weighting and essentially take a massive position in the out of the money call (which would not be possible in real life), we get huge drawdowns and volatility, but the returns are almost two fold. But nobody will sell you a five year call. Others can correct any mistakes or misunderstandings in the above. It hopefully gives a starting point. Read more at: https://en.wikipedia.org/wiki/Modern_portfolio_theory https://en.wikipedia.org/wiki/Option_(finance) The imgur album: https://imgur.com/a/LoBEY\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"472663\",\n \"text\": \"\\\"An Exchange-Traded Fund (ETF) is a special type of mutual fund that is traded on the stock exchange like a stock. To invest, you buy it through a stock broker, just as you would if you were buying an individual stock. When looking at a mutual fund based in the U.S., the easiest way to tell whether or not it is an ETF is by looking at the ticker symbol. Traditional mutual funds have ticker symbols that end in \\\"\\\"X\\\"\\\", and ETFs have ticker symbols that do not end in \\\"\\\"X\\\"\\\". The JPMorgan Emerging Markets Equity Fund, with ticker symbol JFAMX, is a traditional mutual fund, not an ETF. JPMorgan does have ETFs; the JPMorgan Diversified Return Emerging Markets Equity ETF, with ticker symbol JPEM, is an example. This ETF invests in similar stocks as JFAMX; however, because it is an index-based fund instead of an actively managed fund, it has lower fees. If you aren't sure about the ticker symbol, the advertising/prospectus of any ETF should clearly state that it is an ETF. (In the example of JPEM above, they put \\\"\\\"ETF\\\"\\\" right in the fund name.) If you don't see ETF mentioned, it is most likely a traditional mutual fund. Another way to tell is by looking at the \\\"\\\"investment minimums\\\"\\\" of the fund. JFAMX has a minimum initial investment of $1000. ETFs, however, do not have an investment minimum listed; because it is traded like a stock, you simply buy whole shares at whatever the current share price is. So if you look at the \\\"\\\"Fees and Investment Minimums\\\"\\\" section of the JPEM page, you'll see the fees listed, but not any investment minimums.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"350191\",\n \"text\": \"\\\"Things are in fact more complicated. It really depends what you mean by \\\"\\\"ticker\\\"\\\" and who gave you this ticker. There is several codes to identify a security: The Bloomberg code contains a code to identify the exchange as in ALU:FP the FP part refers to Euronext Paris. The RIC code works the same way but with a different convention. Exchanges are identified by the MIC code.(they are in fact divided in market segments with each market segment having a main market segment) ISIN and SEDOL codes do not provide informations about the exchange so they are usually given with a MIC. There is no guarantee that Reuters and Bloomberg won't use the same company code to refer to different company. But they usually use the exchange ticker. This ticker is requested by each company and can be anything. They are accepted most of the time. But sometimes to avoid confusion some requests are rejected. (For instance FBI ticker was refused) For more info read: The evolution of ticker symbols Financial providers like Bloomberg provides services to be informed when a security is added/removed from a market.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"195089\",\n \"text\": \"Willis Group Holdings Set to Join the S&P 500; Fossil Group to Join S&P MidCap 400; Adeptus Health to Join S&P SmallCap 600 notes in part for the S & P case: Willis Group Holdings plc (NYSE:WSH) will replace Fossil Group Inc. (NASD:FOSL) in the S&P 500, and Fossil Group will replace Towers Watson & Co. (NASD:TW) in the S&P MidCap 400 after the close of trading on Monday, January 4. Willis Group is merging with Towers Watson in a deal expected to be completed on or about that date pending final conditions. Post merger, Willis Group Holdings will change its name to Willis Towers Watson plc and trade under the ticker symbol “WLTW”. Fossil has a market capitalization that is more representative of the midcap market space. As of Jan. 8, Fossil is about $1.44B in market cap and Willis is $21.02B for those wondering. Apple with a market cap of $540.58B is 3.26% of the index making the entire index worth approximately $16,582.21B, so Fossil is worth .00868% of the overall index for those wanting some numbers here. Thus, if a company acquires another and becomes bigger than there can be replacements made in those indices that have an artificial number of small members. Alternatively, a member may be removed for lack of representation where it is just so small compared to other companies that may be a better fit as some indices could be viewed as actively managed in a sense. In contrast, there are indices like those from Russell, known for the Russell 2000 small-cap index: Q: Why don't you reconstitute the indexes more often than once a year? A: Maintaining representative indexes must be weighed against the costs associated with making frequent changes to index constituents (namely, buying and selling stocks). The Russell Indexes are annually reconstituted because our research has shown that this strikes a reasonable balance between accuracy and cost. We originally reconstituted our indexes quarterly, then semi-annually, but found these options to be suboptimal. Our extensive research demonstrates that annual reconstitution accurately represents the capitalization segments and minimizes the turnover required to reflect the segments as they change. Thus there can be different scenarios. Then there can be the effect on index funds when price-weighted indices like the Dow Jones Industrial Average has a member that does a stock split that causes some rebalancing too. On the DJIA Divisor: The Dow Jones Industrial Average (DJIA) is a price-weighted index that is calculated by dividing the sum of the prices of the 30 component stocks (Dow Jones Industrial Average components) by a number called the DJIA Divisor or Dow Divisor . The index divisor is updated periodically and adjusted to offset the effect of stock splits, bonus issues or any change in the component stocks included in the DJIA. This is done in order to keep the index value consistent.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"341293\",\n \"text\": \"\\\"When they entered Bankruptcy they changed their stock symbol from AAMR to AAMRQ. The Q tells investors that the company i in Bankruptcy. This i what the SEC says about the Q: \\\"\\\"Q\\\"\\\" Added To Stock Ticker Symbol When a company is involved in bankruptcy proceedings, the letter \\\"\\\"Q\\\"\\\" is added to the end of the company's stock ticker symbol. In most cases, when a company emerges from bankruptcy, the reorganization plan will cancel the existing equity stock and the old shares will be worthless. Given that risk, before purchasing stock in a bankrupt company, investors should read the company's proposed plan of reorganization. For more information about the impact of bankruptcy proceedings on securities, please read our online publication, Corporate Bankruptcy. The risks are they never recover, or that the old shares have nothing to do with new company. Many investors don't understand this. Recently some uninformed investors(?) tried to get a jump on the Twitter IPO by purchasing share of what they thought was Twitter but was instead the bankrupt company Tweeter Home Entertainment. Shares of Tweeter Home Entertainment, a Boston-based consumer electronics chain that filed for bankruptcy in 2007, soared Friday in a case of mistaken identity on Wall Street. Apparently, some investors confused Tweeter, which trades under the symbol TWTRQ, with Twitter and piled into the penny stock. Tweeter, which trades over the counter, opened at 2 cents a share and jumped as much as 15 cents — or 1,800 percent — before regulators halted trading. Almost 15 million shares had changed hands at that point, while the average daily volume is closer to 150,000. Sometimes it does happen that the new company does give some value to the old investors, but more often then not the old investors are completely wiped out.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"3118\",\n \"text\": \"Dividends are normally paid in cash, so don't generally affect your portfolio aside from a slight increase to 'cash'. You get a check for them, or your broker would deposit the funds into a money-market account for you. There is sometimes an option to re-invest dividends, See Westyfresh's answer regarding Dividend Re-Investment Plans. As Tom Au described, the dividends are set by the board of directors and announced. Also as he indicated just before the 'record' date, a stock which pays dividends is worth slightly more (reflecting the value of the dividend that will be paid to anyone holding the stock on the record date) and goes down by the dividend amount immediately after that date (since you'd now have to hold the stock till the next record date to get a dividend) In general unless there's a big change in the landscape (such as in late 2008) most companies pay out about the same dividend each time, and changes to this are sometimes seen by some as 'indicators' of company health and such news can result in movement in the stock price. When you look at a basic quote on a ticker symbol there is usually a line for Div/yeild which gives the amount of dividend paid per share, and the relative yeild (as a percentage of the stock price). If a company has been paying dividends, this field will have values in it, if a company does not pay a dividend it will be blank or say NA (depending on where you get the quote). This is the easiest way to see if a company pays a dividend or not. for example if you look at this quote for Google, you can see it pays no dividend Now, in terms of telling when and how much of a dividend has been paid, most financial sites have the option when viewing a stock chart to show the dividend payments. If you expand the chart to show at least a year, you can see when and how much was paid in terms of dividends. For example you can see from this chart that MSFT pays dividends once a quarter, and used to pay out 13 cents, but recently changed to 16 cents. if you were to float your mouse over one of those icons it would also give the date the dividend was paid.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"397445\",\n \"text\": \"\\\"That share class may not have a ticker symbol though \\\"\\\"Black Rock MSCI ACWI ex-US Index\\\"\\\" does have a ticker for \\\"\\\"Investor A\\\"\\\" shares that is BDOAX. Some funds will have multiple share classes that is a way to have fees be applied in various ways. Mutual fund classes would be the SEC document about this if you want a government source within the US around this. Something else to consider is that if you are investing in a \\\"\\\"Fund of funds\\\"\\\" is that there can be two layers of expense ratios to consider. Vanguard is well-known for keeping its expenses low.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"369424\",\n \"text\": \"\\\"The official source is the most recent Form 13F that Berkshire Hathaway, which is filed with the Securities & Exchange Commission on a quarterly basis . You can find it through the SEC filing search engine, using BRKA as the ticker symbol. and then looking for the filings marked 13-FR or 13-FR/A (the \\\"\\\"/A\\\"\\\" indicates an amended filing). As you can see by looking at the 13-F filed for the quarter ending September 30 , the document isn't pretty or necessarily easy to read, hence the popularity of sites such as those that Chad linked to. It is, though, the truly official source from which websites tracking the Berkshire Hathaway portfolio derive their information.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"323133\",\n \"text\": \"\\\"I said the majority, not ALL. (And the vast majority of people -- again even within the \\\"\\\"sciences\\\"\\\" -- are in fact mediocrities). That doesn't mean it take some \\\"\\\"super-genius\\\"\\\" to see past the fraud, but it does take a sharp mind, AND it then takes an interest and time to look into the evidence (what little there actually is). Many people within the hard sciences are more than capable of seeing through the fraud and foolishness of psychology/psychiatry. Indeed, many *have* done so. (Cf [Feynman](http://www.rationalskepticism.org/psychology/richard-feynman-briefly-on-psychology-t967.html), and of course the aforementioned [John Ioannidis](psychcentral.com/blog/archives/2010/10/19/what-research-can-you-believe/) who has debunked a LOT of so called \\\"\\\"research\\\"\\\" in both psychiatry and other medical \\\"\\\"science\\\"\\\" research). But far more often those with sharp minds are busy with a lot of other endeavors, and so long as they have no driving need, they do not really examine other fields to much dept (in most cases they do not investigate other fields at all). What is more is that psychologists & [psychiatrists themselves know](http://www.youtube.com/watch?v=-P6_FwpVo_s) (and [when put on the spot will admit that there is no real science behind the malarkey](http://www.youtube.com/watch?v=atsCp2SErog) or the drugs) that they sell -- not that they really care of course.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"265404\",\n \"text\": \"What I ended up doing was finding where each ticker of Novo was registered (what exchange), then individually looking up the foreign taxation rules of the containing country. Luckily, most companies only have a few tickers so this wasn't too hard in the end.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"27303\",\n \"text\": \"Options - yes we can :) Options tickers on Yahoo! Finance will be displayed as per new options symbology announced by OCC. The basic parts of new option symbol are: Root symbol + Expiration Year(yy)+ Expiration Month(mm)+ Expiration Day(dd) + Call/Put Indicator (C or P) + Strike price Ex.: AAPL January 19 2013, Put 615 would be AAPL130119P00615000 http://finance.yahoo.com/q?s=AAPL130119P00615000&ql=1 Futures - yes as well (: Ex.: 6A.M12.E would be 6AM12.CME using Yahoo Finance symbology. (simple as that, try it out) Get your major futures symbols from here: http://quotes.ino.com/exchanges/exchange.html?e=CME\",\n \"title\": \"\"\n },\n {\n \"docid\": \"165973\",\n \"text\": \"It depends on what site you're looking on and what exchange they're pulling the data from. Even though funds and stocks are called the same thing, they have different ticker symbols in each country's exchange or could be traded as pink sheet stocks in the US. If a company or fund is based in another country (like Canada or the UK) they probably also trade on that country's exchange (Toronto or London) under a different symbol. This can cause a lot of confusion when researching these tickers.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"278113\",\n \"text\": \"Reading this made me think of [this](https://www.youtube.com/watch?v=-s1s5K52zEQ). I wish you luck if you consider yourself an authority on a subject you have practically no exposure to, but hey, what does a hiring manager know? I mean, you're about to start an internship, so obviously everyone should want to know your opinion on the future of the market.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"97075\",\n \"text\": \"Steve Keen says otherwise, he says Banks CAN create a Quadrillion dollars, as long as there are willing borrowers. : http://www.youtube.com/watch?v=zc_fpGfyqGE. http://www.youtube.com/watch?v=4sSfPkIUHPk&feature=share why does m2 seem like exponential? how can fractional reserve do something like that? unpossible. seems like only an explosive growth in either productivity or profits through slave labor globalization or speculative derivatives can do something like that.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"47276\",\n \"text\": \"Presumably you mean to ask what happens if State Street files chapter 7 bankruptcy, since not all bankruptcy proceedings end in liquidation. SPY is a well known ticker, I can't imagine that there wouldn't be an eager bank willing to pay to pick up that ticker and immediately acquire all the assets related to it. The most likely scenario is that another bank would assume control of the ticker and assets, and the shares would continue trading as they always have. A less likely scenario is that no other financial institution wanted to acquire SPY, and the shares would be liquidated and the proceeds would go to the owners of shares of the ETF. Since the underlying assets are in companies that have actual value, the shares shouldn't trade at much of a discount prior to liquidation. Additionally, if there is a black swan event, there will probably be losses on the underlying assets, so it might even be helpful if the SPY fund was tied up in legal proceedings while everyone gets their heads straight in the market.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"318774\",\n \"text\": \"NYSE started allowing four letter tickers around 2009. NASDAQ allows 4-5 letter tickers. I guess they'll keep increasing when / if needed. Companies are allowed to change tickers, although there are costs. Tickers in the US are assigned through a single entity. Companies that are new need to take something that's open. http://www.wsj.com/articles/SB124296050986346159 I see that you're in Australia, but, since there aren't really that many options to deal with the problem that you mentioned, I'd guess that you'll ultimately do the same. Not sure about how tickers are assigned there though.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"339268\",\n \"text\": \"\\\"You cannot determine this solely by the ticker length. However, there are some conventions that may help steer you there. Nasdaq has 2-4 base letters BATS has 4 base letters NYSE equity securities have 1-4 base letters. NYSE Mkt (formerly Amex) have 1-4 base letters. NYSE Arca has 4 base letters OTC has 4 base letters. Security types other than equities may have additional letters added, and each exchange (and data vendors) have different conventions for how this is handled. So if you see \\\"\\\"T\\\"\\\" for a US-listed security it would be only be either NASDAQ, NYSE or NYSE Mkt. If you see \\\"\\\"ANET\\\"\\\" then you cannot tell which exchange it is listed on. (In this case, ANET Arista Networks is actually a NYSE stock). For some non-equity security types, such as hybrids, and debt instruments, some exchanges add \\\"\\\"P\\\"\\\" to the end for \\\"\\\"preferreds\\\"\\\" (Nasdaq and OTC) and NYSE/NYSE Mkt have a variety of methods (including not adding anything) to the ticker. Examples include NYSE:TFG, NYSEMkt:IPB, Nasdaaq: AGNCP, Nasdaq:OXLCN. It all becomes rather confusing given the changes in conventions over the years. Essentially, you require data that provides you with ticker, listing location and security type. The exchanges allocate security tickers in conjunction with the SEC so there are no overlaps. eg. The same ticker cannot represent two different securities. However, tickers can be re-used. For example, the ticker AB has been used by the following companies:\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"37568\",\n \"text\": \"SECTION | CONTENT :--|:-- Title | Bitcoin explained real easy. Raise Your Frequency S1.E1 Description | Bitcoin explained real easy so anyone can understand what it is and how it works.. You decide which system you prefer: current money system: https://www.youtube.com/watch?v=G9IH-XKQpOI current money system: https://www.youtube.com/watch?v=PhSIfVyvDdM current money system: https://www.youtube.com/watch?v=JuP2hH0Kpro current money system: https://www.youtube.com/watch?v=Bx5Sc3vWefE Bitcoin: https://medium.com/zapchain-magazine/the-10-best-videos-to-watch-to-learn-about-bitcoin-c34f98f2fed... Length | 0:26:48 **** ^(I am a bot, this is an auto-generated reply | )^[Info](https://www.reddit.com/u/video_descriptionbot) ^| ^[Feedback](https://www.reddit.com/message/compose/?to=video_descriptionbot&subject=Feedback) ^| ^(Reply STOP to opt out permanently)\",\n \"title\": \"\"\n },\n {\n \"docid\": \"94159\",\n \"text\": \"\\\"I don't have anything definitive, but in general positions in a company are not affected materially by what is called a corporate action. \\\"\\\"Corp Actions\\\"\\\" can really be anything that affects the details of a stock. Common examples are a ticker change, or exchange change, IPO (ie a new ticker), doing a split, or merging with another ticker. All of these events do not change the total value of people's positions. If a stock splits, you might have more shares, but they are worth less per share. A merger is quite similar to a split. The old company's stock is converted two the new companies stock at some ratio (ie 10 shares become 1 share) and then converted 1-to-1 to the new symbol. Shorting a stock that splits is no different. You shorted 10 shares, but after the split those are now 100 shares, when you exit the position you have to deliver back 100 \\\"\\\"new\\\"\\\" shares, though dollar-for-dollar they are the same total value. I don't see why a merger would affect your short position. The only difference is you are now shorting a different company, so when you exit the position you'll have to deliver shares of the new company back to the brokerage where you \\\"\\\"borrowed\\\"\\\" the shares you shorted.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"252039\",\n \"text\": \"Do you want to know How to Buy Bitcoins or How to Make Money in Bitcoin Investments. First of all, you should know What is Bitcoin? and What is Cryptocurrency? Through our this https://www.youtube.com/watch?v=xDIRVGkeONY video link you will get all the information whatever you want to know about Bitcoins. https://www.youtube.com/watch?v=xDIRVGkeONY\",\n \"title\": \"\"\n },\n {\n \"docid\": \"172703\",\n \"text\": \"No, some of Vanguard's funds are index funds like their Total Stock Market Index and 500 Index. In contrast, there are funds like Vanguard PRIMECAP and Vanguard Wellington that are actively managed. There are index funds in both open-end and exchange-traded formats. VTI is the ticker for Vanguard's Total Stock Market ETF while VTSMX is an open-end mutual fund format. VOO would be the S & P 500 ETF ticker while VFINX is one of the open-end mutual fund tickers, where VIIIX has a really low expense ratio but a pretty stiff minimum to my mind. As a general note, open-end mutual funds will generally have a 5 letter ticker ending in X while an ETF will generally be shorter at 3 or 4 letters in length.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"323749\",\n \"text\": \"\\\"There are a number of ways to measure such things and they are generally called \\\"\\\"sentiment indicators\\\"\\\". The ones that I have seen \\\"\\\"work\\\"\\\", in the sense that they show relatively high readings near market tops and relatively low readings near market bottoms. The problem is that there are no thresholds that work consistently. For example, at one market top a sentiment indicator may read 62. At the next market top that same indicator might read 55. So what threshold do you use next time? Maybe the top will come at 53, or maybe it will not come until 65. There was a time when I could have listed examples for you with the names of the indicators and what they signaled and when. But I gave up on such things years ago after seeing such wide variation. I have been at this a long time (30+ years), and I have not found anything that works as well as we would like at identifying a top in real time. The best I have found (although it does give false signals) is a drop in price coupled with a bearish divergence in breadth. The latter is described in \\\"\\\"Stan Weinstein's Secrets For Profiting in Bull and Bear Markets\\\"\\\". Market bottoms are a little less difficult to identify in real time. One thing I would suggest if you think that there is some way to get a significant edge in investing, is to look at the results of Mark Hulbert's monitoring of newsletters. Virtually all of them rise and fall with the market and almost none are able to beat buy and hold of the Wilshire 5000 over the long term.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"222075\",\n \"text\": \"Oh, God! I remember that thing. Could this be considered *peak bullshit product*? This stupid juicer is one of the best examples of why you shouldn't throw technology at something that isn't a problem. Did people have a problem obtaining juice?! Does WiFi solve that problem? To give a counter example, I reckon this: https://shapertools.com/ is one of the BEST technological solutions to a problem that I've seen in a long time, and could be the beginning of a whole range of smart tools. EDIT: people are doubting that is exists. People are using the early models. I first saw the device while watching this video. https://www.youtube.com/watch?v=lfmrvxB154w&feature=youtu.be&t=3m10s Long video of people using and discussing it: https://www.youtube.com/watch?v=p_wk3q8jWcs If you check YouTube, there are loads of videos. https://www.youtube.com/results?search_query=shaper+origin\",\n \"title\": \"\"\n },\n {\n \"docid\": \"475984\",\n \"text\": \"\\\"Thanks for pointing out [the study](http://papers.ssrn.com/sol3/papers.cfm?abstract_id=1748851). It's a slightly different cause than what I was describing when I posted this. Specifically, they show an effect not when the names get confused, but rather when the name similarity simply brings more attention to the stock. I was surprised nobody mentioned that in response to my post. But also interesting is that they had to control for simple confusion between stock symbols, which implies that ticker confusion has a known effect. So I dug into research on that and quickly found [this study](http://www.efmaefm.org/0EFMAMEETINGS/EFMA%20ANNUAL%20MEETINGS/2010-Aarhus/EFMA2010_0161_fullpaper.pdf) found \\\"\\\"a high positive correlation between returns on two matching stocks with similar ticker symbols\\\"\\\".\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"550661\",\n \"text\": \"Google will be issuing Class C shares (under the ticker symbol GOOCV) to current GOOG holders in the beginning of April. The Class C shares and Class A shares will then change symbols, with the Class C shares trading under GOOG. This was announced on January 30th. Details are in this benzinga article: Projected Trading Timeline March 27 - April 2 Record Date - Payment Date Class C shares commence trading on March 27 as GOOCV on a when issued basis Class A shares continue to trade as GOOG, with entitlement to Class C shares Class A shares will also trade on an ex-distribution basis, without entitlement to the Class C shares, as GOOAV April 3 EX Date The ticker for the Class A shares will change from GOOG to GOOGL The ticker for the Class C shares will change from GOOCV to GOOG and commence regular way trading The ticker for the Class A shares that traded on an ex-distribution basis - GOOAV - will be suspended\",\n \"title\": \"\"\n },\n {\n \"docid\": \"104901\",\n \"text\": \"There's an interesting paper, Does Investor Attention Affect Stock Prices? (Sandhya et al), where researchers look at related stock tickers. When a large cap, better-known stock jumps, smaller firms with similar symbols also rise. Pretty nuts -- I interviewed the author of the paper [here](http://www.tradestreaming.com/?p=3745). There's also a transcript.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"448938\",\n \"text\": \"\\\"The 3-letter tickers are from a different era.... Nowadays the usage of tickers is more of a \\\"\\\"legacy\\\"\\\" tradition rather than a current necessity. As such they're no longer limited to 3 characters. And the characters don't have to be related to the actual name. For example a company named Alphabet is trading on NASDAQ under the ticker \\\"\\\"GOOGL\\\"\\\". It has 5 characters, not 3, and (almost) none of them appear in the name of the company (used to, but not anymore).\\\"\",\n \"title\": \"\"\n }\n]"}}},{"rowIdx":199,"cells":{"query_id":{"kind":"string","value":"334"},"query":{"kind":"string","value":"Depletion of nitric oxide is responsible for vasospasm."},"positive_passages":{"kind":"list like","value":[{"docid":"25079962","text":"CONTEXT Delayed cerebral vasospasm causes permanent neurological deficits or death in at least 15% of patients following otherwise successful treatment for ruptured intracranial aneurysm. Decreased bioavailability of nitric oxide has been associated with the development of cerebral vasospasm. OBJECTIVE To determine whether infusions of nitrite will prevent delayed cerebral vasospasm. DESIGN, SETTING, AND SUBJECTS A total of 14 anesthetized cynomolgus monkeys had an autologous blood clot placed around the right middle cerebral artery. Cerebral arteriography was performed before clot placement and on days 7 and 14 to assess vasospasm. The study was conducted from August 2003 to February 2004. INTERVENTIONS A 90-mg sodium nitrite intravenous solution infused over 24 hours plus a 45-mg sodium nitrite bolus daily (n = 3); a 180-mg sodium nitrite intravenous solution infused over 24 hours (n = 3); or a control saline solution infusion (n = 8). Each was infused continuously for 14 days. MAIN OUTCOME MEASURES Nitrite, S-nitrosothiol, and methemoglobin levels in blood and cerebrospinal fluid and degree of arteriographic vasospasm. RESULTS In control monkeys, mean (SD) cerebrospinal fluid nitrite levels decreased from 3.1 (1.5) micromol/L to 0.4 (0.1) micromol/L at day 7 and to 0.4 (0.4) micromol/L at day 14 (P = .03). All 8 control monkeys developed significant vasospasm of the right middle cerebral artery, which was complicated by stroke and death in 1 animal. Sodium nitrite infusions increased the nitrite and methemoglobin levels (<2.1% of total hemoglobin) in the blood and cerebrospinal fluid without evoking systemic hypotension. Nitrite infusion prevented development of vasospasm (no animals developed significant vasospasm; mean [SD] reduction in right middle cerebral artery area on day 7 after subarachnoid hemorrhage of 8% [9%] in nitrite-treated monkeys vs 47% [5%] in saline-treated controls; P<.001). There was a negative correlation between the concentration of nitrite in cerebrospinal fluid and the degree of cerebral vasospasm (P<.001). Pharmacological effects of nitrite infusion were also associated with the formation of S-nitrosothiol in cerebrospinal fluid. There was no clinical or pathological evidence of nitrite toxicity. CONCLUSION Subacute sodium nitrite infusions prevented delayed cerebral vasospasm in a primate model of subarachnoid hemorrhage.","title":"Nitrite infusions to prevent delayed cerebral vasospasm in a primate model of subarachnoid hemorrhage."}],"string":"[\n {\n \"docid\": \"25079962\",\n \"text\": \"CONTEXT Delayed cerebral vasospasm causes permanent neurological deficits or death in at least 15% of patients following otherwise successful treatment for ruptured intracranial aneurysm. Decreased bioavailability of nitric oxide has been associated with the development of cerebral vasospasm. OBJECTIVE To determine whether infusions of nitrite will prevent delayed cerebral vasospasm. DESIGN, SETTING, AND SUBJECTS A total of 14 anesthetized cynomolgus monkeys had an autologous blood clot placed around the right middle cerebral artery. Cerebral arteriography was performed before clot placement and on days 7 and 14 to assess vasospasm. The study was conducted from August 2003 to February 2004. INTERVENTIONS A 90-mg sodium nitrite intravenous solution infused over 24 hours plus a 45-mg sodium nitrite bolus daily (n = 3); a 180-mg sodium nitrite intravenous solution infused over 24 hours (n = 3); or a control saline solution infusion (n = 8). Each was infused continuously for 14 days. MAIN OUTCOME MEASURES Nitrite, S-nitrosothiol, and methemoglobin levels in blood and cerebrospinal fluid and degree of arteriographic vasospasm. RESULTS In control monkeys, mean (SD) cerebrospinal fluid nitrite levels decreased from 3.1 (1.5) micromol/L to 0.4 (0.1) micromol/L at day 7 and to 0.4 (0.4) micromol/L at day 14 (P = .03). All 8 control monkeys developed significant vasospasm of the right middle cerebral artery, which was complicated by stroke and death in 1 animal. Sodium nitrite infusions increased the nitrite and methemoglobin levels (<2.1% of total hemoglobin) in the blood and cerebrospinal fluid without evoking systemic hypotension. Nitrite infusion prevented development of vasospasm (no animals developed significant vasospasm; mean [SD] reduction in right middle cerebral artery area on day 7 after subarachnoid hemorrhage of 8% [9%] in nitrite-treated monkeys vs 47% [5%] in saline-treated controls; P<.001). There was a negative correlation between the concentration of nitrite in cerebrospinal fluid and the degree of cerebral vasospasm (P<.001). Pharmacological effects of nitrite infusion were also associated with the formation of S-nitrosothiol in cerebrospinal fluid. There was no clinical or pathological evidence of nitrite toxicity. CONCLUSION Subacute sodium nitrite infusions prevented delayed cerebral vasospasm in a primate model of subarachnoid hemorrhage.\",\n \"title\": \"Nitrite infusions to prevent delayed cerebral vasospasm in a primate model of subarachnoid hemorrhage.\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"23100962","text":"Besides synthesizing nitric oxide (NO), purified neuronal NO synthase (nNOS) can produce superoxide (.O2-) at lower L-Arg concentrations. By using electron paramagnetic resonance spin-trapping techniques, we monitored NO and .O2- formation in nNOS-transfected human kidney 293 cells. In control transfected cells, the Ca2+ ionophore A23187 triggered NO generation but no .O2- was seen. With cells in L-Arg-free medium, we observed .O2- formation that increased as the cytosolic L-Arg levels decreased, while NO generation declined. .O2- formation was virtually abolished by the specific NOS blocker, N-nitro-L-arginine methyl ester (L-NAME). Nitrotyrosine, a specific nitration product of peroxynitrite, accumulated in L-Arg-depleted cells but not in control cells. Activation by A23187 was cytotoxic to L-Arg-depleted, but not to control cells, with marked lactate dehydrogenase release. The cytotoxicity was largely prevented by either superoxide dismutase or L-NAME. Thus, with reduced L-Arg availability NOS elicits cytotoxicity by generating .O2- and NO that interact to form the potent oxidant peroxynitrite. Regulating arginine levels may provide a therapeutic approach to disorders involving .O2-/NO-mediated cellular injury.","title":"Nitric oxide synthase generates superoxide and nitric oxide in arginine-depleted cells leading to peroxynitrite-mediated cellular injury."},{"docid":"24338780","text":"BACKGROUND Interferon-gamma (IFN-gamma) is an essential cytokine in the regulation of inflammatory responses in autoimmune diseases. Little is known about its role in inflammatory heart disease. METHODS AND RESULTS We showed that IFN-gamma receptor-deficient mice (IFN-gammaR(-/-)) on a BALB/c background immunized with a peptide derived from cardiac alpha-myosin heavy chain develop severe myocarditis with high mortality. Although myocarditis subsided in wild-type mice after 3 weeks, IFN-gammaR(-/-) mice showed persistent disease. The persistent inflammation was accompanied by vigorous in vitro CD4 T-cell responses and impaired inducible nitric oxide synthase expression, together with evidence of impaired nitric oxide production in IFN-gammaR(-/-) hearts. Treatment of wild-type mice with the nitric oxide synthetase inhibitor N:-nitro-l-arginine-methyl-ester enhanced in vitro CD4 T-cell proliferation and prevented healing of myocarditis. CONCLUSIONS Our data provide evidence that IFN-gamma protects mice from lethal autoimmune myocarditis by inducing the expression of inducible nitric oxide synthase followed by the downregulation of T-cell responses.","title":"Lethal autoimmune myocarditis in interferon-gamma receptor-deficient mice: enhanced disease severity by impaired inducible nitric oxide synthase induction."},{"docid":"46743299","text":"Chronic exercise upregulates endothelial nitric oxide synthase (eNOS) gene expression. Whether the expression of inducible nitric oxide synthase (iNOS) is affected by exercise is unknown. We therefore investigated the effects of chronic exercise on iNOS and eNOS expression in isolated rat aortic endothelial and smooth muscle cells separately. Five-week-old male Wistar rats were randomly divided into control and exercise groups. After 10 weeks of running training, animals were sacrificed under ether anesthesia. The standard curve quantitative competitive reverse transcriptase-polymerase chain reaction method was used to quantify NOS mRNA expression in isolated endothelial/smooth muscle cells. To evaluate the functional role of iNOS, we examined phenylephrine-induced vascular responses with or without pretreatment with aminoguanidine. We found that (1) expression of iNOS and eNOS mRNA in endothelial cells was increased by chronic exercise and (2) chronic exercise blunted phenylephrine-induced vascular responses, probably by increasing NO release via iNOS. Our results show that chronic exercise increases both iNOS and eNOS gene expression in endothelium. These alterations may be partially responsible for the change in vascular response after exercise.","title":"Chronic Exercise Increases Both Inducible and Endothelial Nitric Oxide Synthase Gene Expression in Endothelial Cells of Rat Aorta"},{"docid":"14474178","text":"The objective of the present study was to determine if chicken melanoma-differentiation-associated gene 5 (MDA5) senses infectious bursal disease virus infection to induce innate immunity that bridges to adaptive immunity. During IBDV infection in HD11 cells, IBDV titers and RNA loads increased up to 3.4 × 107 plaque-forming units (PFU)/mL and 1114 ng/µL, respectively, at 24 hours postinfection (hpi). IBDV infection in HD11 cells induced significantly upregulated (p < 0.05) expression levels of chicken MDA5 (59-fold), interferon-β (IFN-β) (693-fold), dsRNA-dependent protein kinase (PKR) (4-fold), 2’, 5’-oligoadenylate synthetase (OAS) (286-fold), myxovirus resistance gene (Mx) (22-fold), interleukin-1β (IL-1β) (5-fold), IL-6 (146-fold), IL-8 (4-fold), IL-10 (4-fold), inducible nitric oxide synthase (iNOS) (15-fold), and major histocompatibility complex class I (MHC class I) (4-fold). Nitric oxide production in the culture supernatants increased significantly (p < 0.05) up to 6.5 μM at 24 hpi. The expressed chMDA5 and IBDV-derived dsRNA were localized in the cytoplasm of HD11 cells during IBDV infection. ChMDA5-knockdown HD11 cells had significantly higher (p < 0.05) IBDV RNA loads at 24 hpi and significantly lower (p < 0.05) nitric oxide production and expression levels of chicken MDA5, IFN-β, PKR, OAS, Mx, IL-1β, IL-6, IL-8, IL-12(p40), IL-18, IL-10, iNOS, MHC class I and CD86 at 24 hpi. In addition, chMDA5 overexpression in HD11 cells resulted in significantly reduced (p < 0.05) IBDV titers and RNA loads and significantly increased (p < 0.05) nitric oxide production at 16 and 24 hpi. It also resulted in significantly higher (p < 0.05) expression levels of chicken MDA5, IFN-β, PKR, OAS, Mx, IL-1β, IL-6, IL-8, IL-12(p40), IL-10 and iNOS at 2 hpi. In conclusion, the results indicate that chMDA5 senses IBDV infection in chicken macrophages, and this is associated with IBDV-induced expression of IFN-β and initiation of an innate immune response that in turn activates the adaptive immune response and limits IBDV replication.","title":"Role of chicken melanoma differentiation-associated gene 5 in induction and activation of innate and adaptive immune responses to infectious bursal disease virus in cultured macrophages"},{"docid":"7155555","text":"Listeria monocytogenes is widely used as a model to study immune responses against intracellular bacteria. It has been shown that neutrophils and macrophages play an important role to restrict bacterial replication in the early phase of primary infection in mice, and that the cytokines interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) are essential for protection. However, the involved signaling pathways and effector mechanisms are still poorly understood. This study investigated mouse strains deficient for the IFN-dependent transcription factors interferon consensus sequence binding protein (ICSBP), interferon regulatory factor (IRF)1 or 2 for their capacity to eliminate Listeria in vivo and in vitro and for production of inducible reactive nitrogen intermediates (RNI) or reactive oxygen intermediates (ROI) in macrophages. ICSBP−/− and to a lesser degree also IRF2−/− mice were highly susceptible to Listeria infection. This correlated with impaired elimination of Listeria from infected peritoneal macrophage (PEM) cultures stimulated with IFN-γ in vitro; in addition these cultures showed reduced and delayed oxidative burst upon IFN-γ stimulation, whereas nitric oxide production was normal. In contrast, mice deficient for IRF1 were not able to produce nitric oxide, but they efficiently controlled Listeria in vivo and in vitro. These results indicate that (a) the ICSBP/IRF2 complex is essential for IFN-γ–mediated protection against Listeria and that (b) ROI together with additional still unknown effector mechanisms may be responsible for the anti-Listeria activity of macrophages, whereas IRF1-induced RNI are not limiting.","title":"Crucial Role of Interferon Consensus Sequence Binding Protein, but neither of Interferon Regulatory Factor 1 nor of Nitric Oxide Synthesis for Protection Against Murine Listeriosis"},{"docid":"23122306","text":"In an experiment to clarify the involvement of oxygen radicals in lung carcinogenesis induced by diesel exhaust particles (DEP), we found that there is a strong relation between lung tumor response and formation of 8-hydroxydeoxyguanosine (8-OHdG) in lung DNA of mice administered DEP by repeated intratracheal instillation. Repeated intratracheal instillation of DEP also induced the activity of cytochrome P-450 reductase in the lungs as a representative enzyme of superoxide generation, and two types of nitric oxide (NO) synthase, cNOS and iNOS, in the lungs. On the other hand, activities of CuZn-superoxide dismutase (SOD) and Mn-SOD antioxidant enzymes were depressed by the instillation of DEP. These results suggest that generation of superoxide, hydroxyI radical, and nitric oxide are increased in epithelial cells in airways, and that the increased superoxide and nitric oxide react very easily to produce peroxynitrite (ONOO(-)). The peroxynitrite also produce hydroxyI radical. The hydroxyl radical may play an important role in carcinogenesis by DEP.","title":"Lung Carcinogenesis by Diesel Exhaust Particles and the Carcinogenic Mechanism Via Active Oxygens."},{"docid":"10697096","text":"BACKGROUND The purpose of this study was to test the hypothesis that vasodilator responses of porcine coronary resistance arteries are increased by exercise training. METHODS AND RESULTS Yucatan miniature swine were randomly divided into groups of exercise-trained (ET) and sedentary (SED) control pigs. ET pigs were placed on a progressive treadmill training program lasting 16 to 20 weeks, and SED pigs remained inactive during the same time period. Coronary resistance arteries 64 to 157 microns in diameter were isolated for in vitro evaluation of relaxation responses to the endothelium-independent dilators sodium nitroprusside (1 x 10(-10) to 1 x 10(-4) mol/L) and adenosine (1 x 10(-10) to 1 x 10(-5) mol/L) and to bradykinin (1 x 10(-13) to 3 x 10(-7) mol/L), an endothelium-dependent agent. Relaxation responses to adenosine and sodium nitroprusside were not altered by exercise training. Endothelium-dependent relaxation to bradykinin was enhanced in coronary resistance arteries from ET pigs (IC50: ET, 0.07 +/- 0.02 nmol/L; SED, 1.59 +/- 0.09 nmol/L). To determine whether prostanoids and/or the nitric oxide synthase pathway were involved in the ET-induced changes in bradykinin-induced vasodilation, responses to bradykinin were examined in coronary resistance arteries from both ET and SED pigs in the presence of indomethacin and in the presence of nitro-monomethyl L-arginine (L-NMMA). Both indomethacin and L-NMMA produced significant inhibition of the bradykinin-induced relaxation in vessels from both groups. Despite decreased bradykinin-induced relaxation after indomethacin, bradykinin-induced vasodilation was still enhanced in vessels from the ET group. L-NMMA caused greater inhibition of the bradykinin-induced relaxation in coronary resistance arteries from ET pigs relative to arteries from SED pigs and eliminated the training-induced enhancement of the bradykinin responses. CONCLUSIONS These results suggest that exercise training enhances bradykinin-induced vasodilation through increased endothelium-derived relaxing factor/nitric oxide production by the L-arginine/nitric oxide synthase pathway.","title":"Vasodilator responses of coronary resistance arteries of exercise-trained pigs."},{"docid":"8536018","text":"Nitric oxide (NO) was identified as a key player in plant defence responses approximately 20 years ago and a large body of evidence has accumulated since then supporting its role as a signalling molecule. However, there are many discrepancies in current NO detection assays and the enzymatic pathways responsible for its synthesis have yet to be determined. This has provoked strong debates concerning the function of NO in plants, even questioning its existence in planta. Here we gather data obtained using the model pathosystem Arabidopsis/Pseudomonas, which confirms the production of NO during the hypersensitive response and supports is role as a trigger of hypersensitive cell death and a mediator of defence gene expression. Finally, we discuss potential sources of NO synthesis, focusing on the role of nitrite as major substrate for NO production during incompatible interactions.","title":"Detection and function of nitric oxide during the hypersensitive response in Arabidopsis thaliana: where there's a will there's a way."},{"docid":"21297708","text":"1. Nitric oxide (NO) has been suggested as a gastrointestinal neurotransmitter, mediating the gastric receptive relaxation and the relaxation in the peristaltic reflex. The aim of the present study was to measure nerve-induced NO formation in vivo in the gastrointestinal tract. 2. Formation of the nitric oxide oxidation products nitrite and nitrate during vagal nerve stimulation were measured in the anaesthetized rabbit. Microdialysis probes were inserted into the wall of the stomach and proximal colon, and nitrite and nitrate in dialysate measured by capillary electrophoresis. 3. During bilateral vagal nerve stimulation there was an increase in nitrite and nitrate formation at the level of the stomach and in nitrite formation at the level of the colon. This increase was inhibited by intravenous administration of the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME 30 mg kg-1). Furthermore, L-NAME significantly increased nerve-induced gastric and colonic contractions, as well as spontaneous colonic contractions. 4. In summary, we present a new methodological procedure for quantification of small changes in nitric oxide formation in vivo. This study provides evidence that nitric oxide is released in the stomach and colonic wall during vagal nerve activity, at concentrations able to cause inhibition of smooth muscle contractions in vivo.","title":"Nerve-induced release of nitric oxide in the rabbit gastrointestinal tract as measured by in vivo microdialysis."},{"docid":"20381484","text":"S-nitrosylation of proteins by nitric oxide is a major mode of signalling in cells. S-nitrosylation can mediate the regulation of a range of proteins, including prominent nuclear proteins, such as HDAC2 (ref. 2) and PARP1 (ref. 3). The high reactivity of the nitric oxide group with protein thiols, but the selective nature of nitrosylation within the cell, implies the existence of targeting mechanisms. Specificity of nitric oxide signalling is often achieved by the binding of nitric oxide synthase (NOS) to target proteins, either directly or through scaffolding proteins such as PSD-95 (ref. 5) and CAPON. As the three principal isoforms of NOS--neuronal NOS (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS)--are primarily non-nuclear, the mechanisms by which nuclear proteins are selectively nitrosylated have been elusive. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is physiologically nitrosylated at its Cys 150 residue. Nitrosylated GAPDH (SNO-GAPDH) binds to Siah1, which possesses a nuclear localization signal, and is transported to the nucleus. Here, we show that SNO-GAPDH physiologically transnitrosylates nuclear proteins, including the deacetylating enzyme sirtuin-1 (SIRT1), histone deacetylase-2 (HDAC2) and DNA-activated protein kinase (DNA-PK). Our findings reveal a novel mechanism for targeted nitrosylation of nuclear proteins and suggest that protein-protein transfer of nitric oxide groups may be a general mechanism in cellular signal transduction.","title":"GAPDH Mediates Nitrosylation of Nuclear Proteins"},{"docid":"42873134","text":"Type 1 and type 2 diabetes are characterized by progressive beta-cell failure. Apoptosis is probably the main form of beta-cell death in both forms of the disease. It has been suggested that the mechanisms leading to nutrient- and cytokine-induced beta-cell death in type 2 and type 1 diabetes, respectively, share the activation of a final common pathway involving interleukin (IL)-1beta, nuclear factor (NF)-kappaB, and Fas. We review herein the similarities and differences between the mechanisms of beta-cell death in type 1 and type 2 diabetes. In the insulitis lesion in type 1 diabetes, invading immune cells produce cytokines, such as IL-1beta, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma. IL-1beta and/or TNF-alpha plus IFN-gamma induce beta-cell apoptosis via the activation of beta-cell gene networks under the control of the transcription factors NF-kappaB and STAT-1. NF-kappaB activation leads to production of nitric oxide (NO) and chemokines and depletion of endoplasmic reticulum (ER) calcium. The execution of beta-cell death occurs through activation of mitogen-activated protein kinases, via triggering of ER stress and by the release of mitochondrial death signals. Chronic exposure to elevated levels of glucose and free fatty acids (FFAs) causes beta-cell dysfunction and may induce beta-cell apoptosis in type 2 diabetes. Exposure to high glucose has dual effects, triggering initially \"glucose hypersensitization\" and later apoptosis, via different mechanisms. High glucose, however, does not induce or activate IL-1beta, NF-kappaB, or inducible nitric oxide synthase in rat or human beta-cells in vitro or in vivo in Psammomys obesus. FFAs may cause beta-cell apoptosis via ER stress, which is NF-kappaB and NO independent. Thus, cytokines and nutrients trigger beta-cell death by fundamentally different mechanisms, namely an NF-kappaB-dependent mechanism that culminates in caspase-3 activation for cytokines and an NF-kappaB-independent mechanism for nutrients. This argues against a unifying hypothesis for the mechanisms of beta-cell death in type 1 and type 2 diabetes and suggests that different approaches will be required to prevent beta-cell death in type 1 and type 2 diabetes.","title":"Mechanisms of pancreatic beta-cell death in type 1 and type 2 diabetes: many differences, few similarities."},{"docid":"2533768","text":"Clinical manifestations of diabetic nephropathy are an expression of diabetic microangiopathy. This review revisits the previously proposed Steno hypothesis and advances our hypothesis that development of endothelial cell dysfunction represents a common pathophysiological pathway of diabetic complications. Specifically, the ability of glucose to scavenge nitric oxide is proposed as the initiation phase of endothelial dysfunction. Gradual accumulation of advanced glycated end products and induction of plasminogen activator inhibitor-1, resulting in the decreased expression of endothelial nitric oxide synthase and reduced generation of nitric oxide, are proposed to be pathophysiologically critical for the maintenance phase of endothelial dysfunction. The proposed conceptual shift toward the role of endothelial dysfunction in diabetic complications may provide new strategies for their prevention.","title":"Workshop: endothelial cell dysfunction leading to diabetic nephropathy : focus on nitric oxide."},{"docid":"38944245","text":"Lung Krüppel-like factor (LKLF/KLF2) is an endothelial transcription factor that is crucially involved in murine vasculogenesis and is specifically regulated by flow in vitro. We now show a relation to local flow variations in the adult human vasculature: decreased LKLF expression was noted at the aorta bifurcations to the iliac and carotid arteries, coinciding with neointima formation. The direct involvement of shear stress in the in vivo expression of LKLF was determined independently by in situ hybridization and laser microbeam microdissection/reverse transcriptase-polymerase chain reaction in a murine carotid artery collar model, in which a 4- to 30-fold induction of LKLF occurred at the high-shear sites. Dissection of the biomechanics of LKLF regulation in vitro demonstrated that steady flow and pulsatile flow induced basal LKLF expression 15- and 36-fold at shear stresses greater than approximately 5 dyne/cm2, whereas cyclic stretch had no effect. Prolonged LKLF induction in the absence of flow changed the expression of angiotensin-converting enzyme, endothelin-1, adrenomedullin, and endothelial nitric oxide synthase to levels similar to those observed under prolonged flow. LKLF repression by siRNA suppressed the flow response of endothelin-1, adrenomedullin, and endothelial nitric oxide synthase (P < 0.05). Thus, we demonstrate that endothelial LKLF is regulated by flow in vivo and is a transcriptional regulator of several endothelial genes that control vascular tone in response to flow.","title":"Endothelial KLF2 links local arterial shear stress levels to the expression of vascular tone-regulating genes."},{"docid":"46328296","text":"Patients with essential hypertension exhibit blunted endothelium-dependent vasodilator responses, which may be largely attributable to reduced bioactivity of nitric oxide (NO). Therefore, we measured the end product of NO, nitrate plus nitrite (nitrogen oxide), and examined the relationship between the degree of hypertension and plasma nitrate plus nitrite levels in patients with essential hypertension. The combined plasma concentration of nitrate plus nitrite, end products of NO metabolism, was reduced in individuals with essential hypertension relative to that in control subjects (15.7+/-1.1 versus 22.8+/-1.4 mmol x L(-1), P<.001); individuals with borderline hypertension showed values that were intermediate between those of the other two groups (18.2+/-1.2 mmol x L(-1), P<.001). The plasma nitrogen oxide concentration showed significant inverse correlations with both systolic and diastolic blood pressures. The basal concentration of nitrogen oxide in the plasma was reduced, at least in the peripheral circulation, in individuals with essential hypertension.","title":"Reduced plasma concentrations of nitrogen oxide in individuals with essential hypertension."},{"docid":"7230315","text":"The high-output pathway of nitric oxide production helps protect mice from infection by several pathogens, including Mycobacterium tuberculosis. However, based on studies of cells cultured from blood, it is controversial whether human mononuclear phagocytes can express the corresponding inducible nitric oxide synthase (iNOS;NOS2). The present study examined alveolar macrophages fixed directly after bronchopulmonary lavage. An average of 65% of the macrophages from 11 of 11 patients with untreated, culture-positive pulmonary tuberculosis reacted with an antibody documented herein to be monospecific for human NOS2. In contrast, a mean of 10% of bronchoalveolar lavage cells were positive from each of five clinically normal subjects. Tuberculosis patients' macrophages displayed diaphorase activity in the same proportion that they stained for NOS2, under assay conditions wherein the diaphorase reaction was strictly dependent on NOS2 expression. Bronchoalveolar lavage specimens also contained NOS2 mRNA. Thus, macrophages in the lungs of people with clinically active Mycobacterium tuberculosis infection often express catalytically competent NOS2.","title":"Inducible nitric oxide synthase in pulmonary alveolar macrophages from patients with tuberculosis"},{"docid":"6580081","text":"Ischemia-reperfusion injury is, at least in part, responsible for the morbidity associated with liver surgery under total vascular exclusion or after liver transplantation. The pathophysiology of hepatic ischemia-reperfusion includes a number of mechanisms that contribute to various degrees in the overall injury. Some of the topics discussed in this review include cellular mechanisms of injury, formation of pro- and anti-inflammatory mediators, expression of adhesion molecules, and the role of oxidant stress during the inflammatory response. Furthermore, the roles of nitric oxide in preventing microcirculatory disturbances and as a substrate for peroxynitrite formation are reviewed. In addition, emerging mechanisms of protection by ischemic preconditioning are discussed. On the basis of current knowledge, preconditioning or pharmacological interventions that mimic these effects have the greatest potential to improve clinical outcome in liver surgery involving ischemic stress and reperfusion.","title":"Molecular mechanisms of hepatic ischemia-reperfusion injury and preconditioning."},{"docid":"14711483","text":"CONTEXT Vaso-occlusion is central to the painful crises and acute and chronic organ damage in sickle cell disease. Abnormal nitric oxide-dependent regulation of vascular tone, adhesion, platelet activation, and inflammation contributes to the pathophysiology of vaso-occlusion. Nitric oxide may have promise as a mechanism-of-disease-based therapy for treatment of vaso-occlusion. OBJECTIVE To explore the efficacy and safety of inhaled nitric oxide (INO) for treatment of vaso-occlusive crisis in pediatric patients. DESIGN Prospective, double-blind, placebo-controlled, randomized clinical trial with enrollment between September 1999 and October 2001. SETTING Urban, tertiary care children's hospital in the United States. PARTICIPANTS Twenty patients aged 10 to 21 years with sickle cell disease and severe acute vaso-occlusive crisis. INTERVENTION Patients were randomly assigned to receive INO (80 ppm with 21% final concentration of inspired oxygen; n = 10), or placebo (21% inspired oxygen; n = 10) for 4 hours. MAIN OUTCOME MEASURES Change in pain at 4 hours of inhalation compared with preinhalation pain, measured on a 10-cm visual analog scale (VAS); secondary outcome measures were pain over 6 hours, parenteral narcotic use over 24 hours, duration of hospitalization, blood pressure, oxygen saturation, and methemoglobin concentration. RESULTS Preinhalation VAS pain scores were similar in the INO and placebo groups (P =.80). The decrease in VAS pain scores at 4 hours was 2.0 cm in the INO group and 1.2 cm in the placebo group (P =.37). Repeated-measures analysis of variance for hourly pain scores showed a 1-cm/h greater reduction in the INO group than the placebo group (P =.02). Morphine use over 6 hours was significantly less in the INO group (mean cumulative use, 0.29 vs 0.44 mg/kg; P =.03) but was not different over 4 hours (0.26 vs 0.32 mg/kg; P =.21) or 24 hours (0.63 vs 0.91 mg/kg; P =.15). Duration of hospitalization was 78 and 100 hours in the INO and placebo groups, respectively (P =.19). No INO toxicity was observed. CONCLUSIONS Results of this exploratory study suggest that INO may be beneficial for acute vaso-occlusive crisis. These preliminary results warrant further investigation.","title":"Preliminary assessment of inhaled nitric oxide for acute vaso-occlusive crisis in pediatric patients with sickle cell disease."},{"docid":"12582729","text":"BACKGROUND Upregulated by atheroprotective flow, the transcription factor Krüppel-like factor 2 (KLF2) is crucial for maintaining endothelial function. MicroRNAs (miRNAs) are noncoding small RNAs that regulate gene expression at the posttranscriptional level. We examined the role of miRNAs, particularly miR-92a, in the atheroprotective flow-regulated KLF2. METHODS AND RESULTS Dicer knockdown increased the level of KLF2 mRNA in human umbilical vein endothelial cells, suggesting that KLF2 is regulated by miRNA. In silico analysis predicted that miR-92a could bind to the 3' untranslated region of KLF2 mRNA. Overexpression of miR-92a decreased the expression of KLF2 and the KLF2-regulated endothelial nitric oxide synthase and thrombomodulin at mRNA and protein levels. A complementary finding is that miR-92a inhibitor increased the mRNA and protein expression of KLF2, endothelial nitric oxide synthase, and thrombomodulin. Subsequent studies revealed that atheroprotective laminar flow downregulated the level of miR-92a precursor to induce KLF2, and the level of this flow-induced KLF2 was reduced by miR-92a precursor. Furthermore, miR-92a level was lower in human umbilical vein endothelial cells exposed to the atheroprotective pulsatile shear flow than under atheroprone oscillatory shear flow. Anti-Ago1/2 immunoprecipitation coupled with real-time polymerase chain reaction revealed that pulsatile shear flow decreased the functional targeting of miR-92a precursor/KLF2 mRNA in human umbilical vein endothelial cells. Consistent with these findings, mouse carotid arteries receiving miR-92a precursor exhibited impaired vasodilatory response to flow. CONCLUSIONS Atheroprotective flow patterns decrease the level of miR-92a, which in turn increases KLF2 expression to maintain endothelial homeostasis.","title":"Flow-Dependent Regulation of Kruppel-Like Factor 2 Is Mediated by MicroRNA-92a."},{"docid":"15561961","text":"Hypercholesterolemia is associated with impairments in endothelium-dependent vascular relaxations. Paradoxically, endothelial production of nitrogen oxides is increased in early stages of hypercholesterolemia. Prior work has shown that oxidized low density lipoprotein (LDL) has both stimulatory and inhibitory effects on endothelial nitric oxide synthase expression (eNOS) and has focused on lysophosphatidyl choline (LPC) as a component of oxidized LDL which may modulate this effect. Another biologically active component of oxidized LDL is 13-hydroperoxyoctadecadienoic acid (13-HPODE), an oxidized form of linoleic acid. The purpose of this study was to determine the effect of HPODE on the expression of eNOS in bovine aortic endothelial cells (BAECs). Twenty four hour treatment of endothelial cells with HPODE caused a dose-dependent increase in eNOS mRNA levels as assessed by Northern analysis. The time response studies show that HPODE treatment significantly increased eNOS mRNA levels at 12 and 24 h. Concomitant with the increase in eNOS mRNA levels, 20 microM HPODE treatment significantly increased eNOS protein content and enzyme activity. Nuclear run-on studies indicated that the rate of transcription of eNOS gene was significantly elevated 4 h after HPODE treatment when compared to control cultures. Also, actinomycin D studies demonstrated that the half-life of eNOS mRNA was increased from 6 h to 12 h by HPODE treatment. Thus, HPODE-induced up-regulation of eNOS expression is mediated by both transcriptional and posttranscriptional mechanisms. These observations suggest that endothelial cells may attempt to compensate for oxidative injury by increasing expression of eNOS in early stages of hypercholesterolemia.","title":"expression by oxidized linoleic"},{"docid":"28207326","text":"Vascular endothelial growth factor-A (VEGF-A) is a protein secreted by podocytes that is necessary for survival of endothelial cells, podocytes, and mesangial cells. VEGF-A regulates slit-diaphragm signaling and podocyte shape via VEGF-receptor 2-nephrin-nck-actin interactions. Chronic hyperglycemia-induced excess podocyte VEGF-A and low endothelial nitric oxide drive the development and the progression of diabetic nephropathy. The abnormal cross-talk between VEGF-A and nitric oxide pathways is fueled by the diabetic milieu, resulting in increased oxidative stress. Recent findings on these pathogenic molecular mechanisms provide new potential targets for therapy for diabetic renal disease.","title":"VEGF and podocytes in diabetic nephropathy."},{"docid":"26658659","text":"Hydrogen sulfide (H(2)S) was recently discovered to be synthesized in mammalian tissues by several different enzymes. Numerous studies have shown that H(2)S has vasodilator and antihypertensive effects in the cardiovascular system. However, intracellular mechanisms of the H(2)S-induced vasodilation and its interactions with other endothelium-derived relaxing factors, such as nitric oxide (NO), remain unclear. We investigated whether H(2)S directly regulates endothelial NO synthase (eNOS) activity and NO production in endothelial cells. NaHS, a H(2)S donor, dose-dependently increased NO production in cultured endothelial cells. This effect was abolished by a calcium chelator (BAPTA-AM), but not by the absence of extracellular calcium. The NaHS-induced NO production was partially blocked by inhibitors of ryanodine receptor (dantrolene) or inositol 1,4,5-triphosphate receptor (xestospongin C). NaHS significantly increased intracellular calcium concentrations, and this effect was attenuated by dantrolene or xestospongin C. NaHS induced phosphorylation of eNOS at the activating phosphoserine residue 1179. The NaHS-induced eNOS phosphorylation and NO production were not affected by a PI3K/Akt inhibitor (wortmannin). The data of this study suggest that H(2)S directly acts on endothelial cells to induce eNOS activation and NO production by releasing calcium from the intracellular store in endoplasmic reticulum, which may explain one of mechanisms of its vasodilator function.","title":"Hydrogen sulfide increases nitric oxide production with calcium-dependent activation of endothelial nitric oxide synthase in endothelial cells."},{"docid":"5785219","text":"Nitric oxide (NO) is a product of L-arginine metabolism that suppresses cellular oxidative metabolism through the inhibition of tricarboxylic acid cycle and electron transport chain enzymes. The impact of NO synthase (NOS) activity on specific pathways of glucose metabolism in freshly harvested and overnight-cultured rat resident peritoneal macrophages, at rest and after stimulation with zymosan, was investigated using radiolabeled glucose. NOS activity was modulated through the L-arginine concentration in culture media and the use of its specific inhibitor, NG-monomethyl-L-arginine, and quantitated using radiolabeled L-arginine. Results demonstrated that NOS activity was associated with increased glucose disappearance, glycolysis, and hexose monophosphate shunt activity and, in line with the known inhibition of oxidative metabolism associated with the production of NO, with a decrease in the flux of glucose and butyrate carbon through the tricarboxylic acid cycle. In addition, the relative increase in glucose utilization that follows zymosan stimulation was enhanced by treatments that suppressed NOS activity. These results demonstrate that the characteristics of glucose metabolism by macrophages are, to a significant extent, determined by products of NOS.","title":"Modulation of glucose metabolism in macrophages by products of nitric oxide synthase."},{"docid":"6923795","text":"Cytochrome P450 (P450)-dependent metabolites of arachidonic acid, the epoxyeicosatrienoic acids (EETs), are proposed to be endothelium-derived hyperpolarizing factors (EDHF) that affect vascular tone; however, the effects of EDHF on endothelial-derived nitric oxide biosynthesis remain unknown. We examined the regulation of endothelial nitric-oxide synthase (eNOS) by EDHF and investigated the relevant signaling pathways involved. The P450 epoxygenases CYP102 F87V mutant, CYP2C11-CYPOR, and CYP2J2 were transfected into cultured bovine aortic endothelial cells, and the effects of endogenously formed or exogenously applied EETs on eNOS expression and activity were assessed. Transfection with the P450 epoxygenases led to increased eNOS protein expression, an effect that was attenuated by cotreatment with the P450 inhibitor 17-ODYA. Northern analysis demonstrated that P450 transfection led to increased eNOS mRNA levels consistent with an effect at the pretranslational level. P450 epoxygenase transfection resulted in increased eNOS activity as measured by the conversion of L-arginine to L-citrulline. Addition of synthetic EETs (50-200 nM) to the culture media also increased eNOS expression and activity. Treatment with mitogen-activated protein kinase (MAPK), MAPK kinase, and protein kinase C inhibitors apigenin, 2'-amino-3'-methoxyflavone (PD98059), and 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7), respectively, significantly inhibited the effects of P450 transfection on eNOS expression. Overexpression of P450 epoxygenases or addition of synthetic EETs increased Thr495 phosphorylation of eNOS, an effect that was inhibited by both apigenin and PD98059. Overexpression of P450 epoxygenases in rats resulted in increased aortic eNOS expression, providing direct evidence that EDHF can influence vascular eNOS levels in vivo. Based on this data, we conclude that EDHF up-regulates eNOS via activation of MAPK and protein kinase C signaling pathways.","title":"Up-regulation of endothelial nitric-oxide synthase by endothelium-derived hyperpolarizing factor involves mitogen-activated protein kinase and protein kinase C signaling pathways."},{"docid":"24705390","text":"BACKGROUND & AIMS Helicobacter pylori is an important etiologic factor in the development of gastric cancer. The aim of this study was to analyze the role of H. pylori infections in the induction of mutagenic events in gastric epithelial cells. The effect of a high-salt diet as a genotoxic risk factor was also investigated. METHODS Big Blue transgenic male mice (C57Bl/6) were inoculated with H. pylori (strain SS1) or Helicobacter felis (strain CS1) for 6 and 12 months. The frequency and spectrum of mutations at the stomach level were assessed. Inflammatory host response and inducible nitric oxide synthase (iNOS) expression by reverse-transcription polymerase chain reaction and immunohistochemistry analysis were also performed. RESULTS After 6 months, the gastric mutant frequency was 4-fold and 1.7-fold higher in mice infected with H. pylori and H. felis, respectively, than in uninfected mice. It was associated with a high frequency of transversions (AT --> CG and GC --> TA) known to result from oxidative damages. The Helicobacter-infected mice exhibited severe gastritis and a high level of iNOS messenger RNA expression. Hyperplasia developed 12 months after inoculation, and both the mutagenic effects and iNOS expression decreased in H. pylori- and H. felis-infected mice. No synergistic effects of a high-salt diet and Helicobacter infection were observed regarding the frequency of gastric mutation. CONCLUSIONS A direct gastric mutagenic effect due to H. pylori infection in the Big Blue transgenic mouse model has been shown 6 months after inoculation. This genotoxicity can be attributable to oxidative DNA damage involving the inflammatory host response.","title":"Chronic Helicobacter pylori infections induce gastric mutations in mice."},{"docid":"22995164","text":"Nitrosoglutathione [(GSNO), 500 nmol/l] relaxed the norepinephrine precontracted rat aortic rings. The relaxation effect was pronouncedly enhanced by H2S- and HS−-donor NaHS (30 μmol/l) at 7.5 pH but not at 6.3 pH. To study molecular mechanism of this effect, we investigated whether NaHS can release NO from NO donors. Using an electron paramagnetic resonance spectroscopy method of spin trap and by measuring the NO oxidation product, which is nitrite, by the Griess reaction, we report that NaHS released NO from nitrosothiols, namely from GSNO, S-nitroso-N-acetyl-dl-penicillamine (SNAP), from metal nitrosyl complex nitroprusside (SNP) and from rat brain homogenate and murine L1210 leukaemia cells. From the observation that the releasing effect was more pronounced at 8.0 pH than 6.0 pH, we suppose that HS−, rather than H2S, is responsible for the NO-releasing effect. Since in mammals, H2S and HS− are produced endogenously, we assume that their effect to release NO from nitrosothiols and from metal nitrosyl complexes are responsible for some of their biological activities and that this mechanism may be involved in S-nitrosothiol-signalling reactions.","title":"H2S and HS− donor NaHS releases nitric oxide from nitrosothiols, metal nitrosyl complex, brain homogenate and murine L1210 leukaemia cells"},{"docid":"32985041","text":"Nitric oxide (NO) has been linked to numerous physiological and pathophysiological events that are not readily explained by the well established effects of NO on soluble guanylyl cyclase. Exogenous NO S-nitrosylates cysteine residues in proteins, but whether this is an important function of endogenous NO is unclear. Here, using a new proteomic approach, we identify a population of proteins that are endogenously S-nitrosylated, and demonstrate the loss of this modification in mice harbouring a genomic deletion of neuronal NO synthase (nNOS). Targets of NO include metabolic, structural and signalling proteins that may be effectors for neuronally generated NO. These findings establish protein S-nitrosylation as a physiological signalling mechanism for nNOS.","title":"Protein S-nitrosylation: a physiological signal for neuronal nitric oxide"},{"docid":"79447","text":"OBJECTIVE The purpose of this study was to characterize the relationship between adipose tissue phenotype and depot-specific microvascular function in fat. METHODS AND RESULTS In 30 obese subjects (age 42±11 years, body mass index 46±11 kg/m(2)) undergoing bariatric surgery, we intraoperatively collected visceral and subcutaneous adipose tissue and characterized depot-specific adipose phenotypes. We assessed vasomotor function of the adipose microvasculature using videomicroscopy of small arterioles (75-250 μm) isolated from different fat compartments. Endothelium-dependent, acetylcholine-mediated vasodilation was severely impaired in visceral arterioles, compared to the subcutaneous depot (P<0.001 by ANOVA). Nonendothelium dependent responses to papaverine and nitroprusside were similar. Endothelial nitric oxide synthase inhibition with N(ω)-nitro-l-arginine methyl ester reduced subcutaneous vasodilation but had no effect on severely blunted visceral arteriolar responses. Visceral fat exhibited greater expression of proinflammatory, oxidative stress-related, hypoxia-induced, and proangiogenic genes; increased activated macrophage populations; and had a higher capacity for cytokine production ex vivo. CONCLUSIONS Our findings provide clinical evidence that the visceral microenvironment may be intrinsically toxic to arterial health providing a potential mechanism by which visceral adiposity burden is linked to atherosclerotic vascular disease. Our findings also support the evolving concept that both adipose tissue quality and quantity may play significant roles in shaping cardiovascular phenotypes in human obesity.","title":"Arteriolar function in visceral adipose tissue is impaired in human obesity."},{"docid":"11181416","text":"Because arginase hydrolyzes arginine to produce ornithine and urea, it has the potential to regulate nitric oxide (NO) and polyamine synthesis. We tested whether expression of the cytosolic isoform of arginase (arginase I) was limiting for NO or polyamine production by activated RAW 264.7 macrophage cells. RAW 264.7 cells, stably transfected to overexpress arginase I or beta-galactosidase, were treated with interferon-gamma to induce type 2 NO synthase or with lipopolysaccharide or 8-bromo-cAMP (8-BrcAMP) to induce ornithine decarboxylase. Overexpression of arginase I had no effect on NO synthesis. In contrast, cells overexpressing arginase I produced twice as much putrescine after activation than did cells expressing beta-galactosidase. Cells overexpressing arginase I also produced more spermidine after treatment with 8-BrcAMP than did cells expressing beta-galactosidase. Thus endogenous levels of arginase I are limiting for polyamine synthesis, but not for NO synthesis, by activated macrophage cells. This study also demonstrates that it is possible to alter arginase I levels sufficiently to affect polyamine synthesis without affecting induced NO synthesis.","title":"Arginase I: a limiting factor for nitric oxide and polyamine synthesis by activated macrophages?"},{"docid":"43048059","text":"AIMS The present study aims to investigate the interaction between nitric oxide (NO) and hydrogen sulfide (H(2)S), the two important gaseous mediators in rat hearts. METHODS AND RESULTS Intracellular calcium in isolated cardiomyocytes was measured with a spectrofluorometric method using Fura-2. Myocyte contractility was measured with a video edge system. NaHS (50 µM, an H(2)S donor) had no significant effect on the resting calcium level, electrically induced (EI) calcium transients, and cell contractility in ventricular myocytes. Stimulating endogenous NO production with l-arginine or exogenous application of NO donors [sodium nitroprusside (SNP) and 2-(N,N-diethylamino)-diazenolate-2-oxide] decreased myocyte twitch amplitudes accompanied by slower velocities of both cell contraction and relaxation. Surprisingly, NaHS reversed the negative inotropic and lusitropic effects of the above three NO-increasing agents. In addition, the mixture of SNP + NaHS increased, whereas SNP alone decreased, the resting calcium level and the amplitudes of EI calcium transients. Angeli's salt, a nitroxyl anion (HNO) donor, mimicked the effect of SNP + NaHS on calcium handling and myocyte contractility. Three thiols, N-acetyl-cysteine, l-cysteine, and glutathione, abolished the effects of HNO and SNP + NaHS on myocyte contraction. Neither Rp-cAMP [a protein kinase A (PKA) inhibitor] nor Rp-cGMP [a protein kinase G (PKG) inhibitor] affected the effects of SNP + NaHS, suggesting a cAMP/PKA- or cGMP/PKG-independent mechanism. CONCLUSION H(2)S may interact with NO to form a thiol sensitive molecule (probably HNO) which produces positive inotropic and lusitropic effects. Our findings may shed light on the interaction of NO and H(2)S and provide new clues to treat cardiovascular diseases.","title":"Hydrogen sulfide interacts with nitric oxide in the heart: possible involvement of nitroxyl."},{"docid":"23513718","text":"Responses of cerebral blood vessels to nitric oxide (NO) are mediated by soluble guanylate cyclase (sGC)-dependent and potentially by sGC-independent mechanisms. One sGC-independent mechanism by which NO may produce vasodilatation is inhibition of formation of a vasoconstrictor metabolite produced through the cytochrome P450 pathway. In these experiments, we examined the hypothesis that dilatation of cerebral microvessels in response to NO is dependent on activation of sGC. Diameters of cerebral arterioles (baseline diameter=94+/-5 micrometers, mean+/-S.E.) were measured using a closed cranial window in anesthetized rabbits. Under control conditions, YC-1 [3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole], an NO-independent activator of sGC, produced vasodilation that was blocked by ODQ (1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one)(10 microM), an inhibitor of sGC. These findings indicate that sGC is functionally important in cerebral arterioles. In addition, acetylcholine (which stimulates endogenous production of NO by endothelium) produced dilatation of cerebral arterioles that was inhibited by ODQ. For example, 1 microM acetylcholine dilated cerebral arterioles by 34+/-7 and 5+/-1% in the absence and presence of ODQ (10 microM), respectively. Increases in arteriolar diameter in response to sodium nitroprusside (1 microM, an NO donor) were inhibited by approximately 80% by ODQ, but were not affected by 17-ODYA (10 microM) or clotrimazole (10 microM), inhibitors of the cytochrome P450 pathway. Thus, dilatation of the cerebral microcirculation in response to exogenously applied and endogenously produced NO is dependent, in large part, on activation of sGC.","title":"Role of soluble guanylate cyclase in dilator responses of the cerebral microcirculation."}],"string":"[\n {\n \"docid\": \"23100962\",\n \"text\": \"Besides synthesizing nitric oxide (NO), purified neuronal NO synthase (nNOS) can produce superoxide (.O2-) at lower L-Arg concentrations. By using electron paramagnetic resonance spin-trapping techniques, we monitored NO and .O2- formation in nNOS-transfected human kidney 293 cells. In control transfected cells, the Ca2+ ionophore A23187 triggered NO generation but no .O2- was seen. With cells in L-Arg-free medium, we observed .O2- formation that increased as the cytosolic L-Arg levels decreased, while NO generation declined. .O2- formation was virtually abolished by the specific NOS blocker, N-nitro-L-arginine methyl ester (L-NAME). Nitrotyrosine, a specific nitration product of peroxynitrite, accumulated in L-Arg-depleted cells but not in control cells. Activation by A23187 was cytotoxic to L-Arg-depleted, but not to control cells, with marked lactate dehydrogenase release. The cytotoxicity was largely prevented by either superoxide dismutase or L-NAME. Thus, with reduced L-Arg availability NOS elicits cytotoxicity by generating .O2- and NO that interact to form the potent oxidant peroxynitrite. Regulating arginine levels may provide a therapeutic approach to disorders involving .O2-/NO-mediated cellular injury.\",\n \"title\": \"Nitric oxide synthase generates superoxide and nitric oxide in arginine-depleted cells leading to peroxynitrite-mediated cellular injury.\"\n },\n {\n \"docid\": \"24338780\",\n \"text\": \"BACKGROUND Interferon-gamma (IFN-gamma) is an essential cytokine in the regulation of inflammatory responses in autoimmune diseases. Little is known about its role in inflammatory heart disease. METHODS AND RESULTS We showed that IFN-gamma receptor-deficient mice (IFN-gammaR(-/-)) on a BALB/c background immunized with a peptide derived from cardiac alpha-myosin heavy chain develop severe myocarditis with high mortality. Although myocarditis subsided in wild-type mice after 3 weeks, IFN-gammaR(-/-) mice showed persistent disease. The persistent inflammation was accompanied by vigorous in vitro CD4 T-cell responses and impaired inducible nitric oxide synthase expression, together with evidence of impaired nitric oxide production in IFN-gammaR(-/-) hearts. Treatment of wild-type mice with the nitric oxide synthetase inhibitor N:-nitro-l-arginine-methyl-ester enhanced in vitro CD4 T-cell proliferation and prevented healing of myocarditis. CONCLUSIONS Our data provide evidence that IFN-gamma protects mice from lethal autoimmune myocarditis by inducing the expression of inducible nitric oxide synthase followed by the downregulation of T-cell responses.\",\n \"title\": \"Lethal autoimmune myocarditis in interferon-gamma receptor-deficient mice: enhanced disease severity by impaired inducible nitric oxide synthase induction.\"\n },\n {\n \"docid\": \"46743299\",\n \"text\": \"Chronic exercise upregulates endothelial nitric oxide synthase (eNOS) gene expression. Whether the expression of inducible nitric oxide synthase (iNOS) is affected by exercise is unknown. We therefore investigated the effects of chronic exercise on iNOS and eNOS expression in isolated rat aortic endothelial and smooth muscle cells separately. Five-week-old male Wistar rats were randomly divided into control and exercise groups. After 10 weeks of running training, animals were sacrificed under ether anesthesia. The standard curve quantitative competitive reverse transcriptase-polymerase chain reaction method was used to quantify NOS mRNA expression in isolated endothelial/smooth muscle cells. To evaluate the functional role of iNOS, we examined phenylephrine-induced vascular responses with or without pretreatment with aminoguanidine. We found that (1) expression of iNOS and eNOS mRNA in endothelial cells was increased by chronic exercise and (2) chronic exercise blunted phenylephrine-induced vascular responses, probably by increasing NO release via iNOS. Our results show that chronic exercise increases both iNOS and eNOS gene expression in endothelium. These alterations may be partially responsible for the change in vascular response after exercise.\",\n \"title\": \"Chronic Exercise Increases Both Inducible and Endothelial Nitric Oxide Synthase Gene Expression in Endothelial Cells of Rat Aorta\"\n },\n {\n \"docid\": \"14474178\",\n \"text\": \"The objective of the present study was to determine if chicken melanoma-differentiation-associated gene 5 (MDA5) senses infectious bursal disease virus infection to induce innate immunity that bridges to adaptive immunity. During IBDV infection in HD11 cells, IBDV titers and RNA loads increased up to 3.4 × 107 plaque-forming units (PFU)/mL and 1114 ng/µL, respectively, at 24 hours postinfection (hpi). IBDV infection in HD11 cells induced significantly upregulated (p < 0.05) expression levels of chicken MDA5 (59-fold), interferon-β (IFN-β) (693-fold), dsRNA-dependent protein kinase (PKR) (4-fold), 2’, 5’-oligoadenylate synthetase (OAS) (286-fold), myxovirus resistance gene (Mx) (22-fold), interleukin-1β (IL-1β) (5-fold), IL-6 (146-fold), IL-8 (4-fold), IL-10 (4-fold), inducible nitric oxide synthase (iNOS) (15-fold), and major histocompatibility complex class I (MHC class I) (4-fold). Nitric oxide production in the culture supernatants increased significantly (p < 0.05) up to 6.5 μM at 24 hpi. The expressed chMDA5 and IBDV-derived dsRNA were localized in the cytoplasm of HD11 cells during IBDV infection. ChMDA5-knockdown HD11 cells had significantly higher (p < 0.05) IBDV RNA loads at 24 hpi and significantly lower (p < 0.05) nitric oxide production and expression levels of chicken MDA5, IFN-β, PKR, OAS, Mx, IL-1β, IL-6, IL-8, IL-12(p40), IL-18, IL-10, iNOS, MHC class I and CD86 at 24 hpi. In addition, chMDA5 overexpression in HD11 cells resulted in significantly reduced (p < 0.05) IBDV titers and RNA loads and significantly increased (p < 0.05) nitric oxide production at 16 and 24 hpi. It also resulted in significantly higher (p < 0.05) expression levels of chicken MDA5, IFN-β, PKR, OAS, Mx, IL-1β, IL-6, IL-8, IL-12(p40), IL-10 and iNOS at 2 hpi. In conclusion, the results indicate that chMDA5 senses IBDV infection in chicken macrophages, and this is associated with IBDV-induced expression of IFN-β and initiation of an innate immune response that in turn activates the adaptive immune response and limits IBDV replication.\",\n \"title\": \"Role of chicken melanoma differentiation-associated gene 5 in induction and activation of innate and adaptive immune responses to infectious bursal disease virus in cultured macrophages\"\n },\n {\n \"docid\": \"7155555\",\n \"text\": \"Listeria monocytogenes is widely used as a model to study immune responses against intracellular bacteria. It has been shown that neutrophils and macrophages play an important role to restrict bacterial replication in the early phase of primary infection in mice, and that the cytokines interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) are essential for protection. However, the involved signaling pathways and effector mechanisms are still poorly understood. This study investigated mouse strains deficient for the IFN-dependent transcription factors interferon consensus sequence binding protein (ICSBP), interferon regulatory factor (IRF)1 or 2 for their capacity to eliminate Listeria in vivo and in vitro and for production of inducible reactive nitrogen intermediates (RNI) or reactive oxygen intermediates (ROI) in macrophages. ICSBP−/− and to a lesser degree also IRF2−/− mice were highly susceptible to Listeria infection. This correlated with impaired elimination of Listeria from infected peritoneal macrophage (PEM) cultures stimulated with IFN-γ in vitro; in addition these cultures showed reduced and delayed oxidative burst upon IFN-γ stimulation, whereas nitric oxide production was normal. In contrast, mice deficient for IRF1 were not able to produce nitric oxide, but they efficiently controlled Listeria in vivo and in vitro. These results indicate that (a) the ICSBP/IRF2 complex is essential for IFN-γ–mediated protection against Listeria and that (b) ROI together with additional still unknown effector mechanisms may be responsible for the anti-Listeria activity of macrophages, whereas IRF1-induced RNI are not limiting.\",\n \"title\": \"Crucial Role of Interferon Consensus Sequence Binding Protein, but neither of Interferon Regulatory Factor 1 nor of Nitric Oxide Synthesis for Protection Against Murine Listeriosis\"\n },\n {\n \"docid\": \"23122306\",\n \"text\": \"In an experiment to clarify the involvement of oxygen radicals in lung carcinogenesis induced by diesel exhaust particles (DEP), we found that there is a strong relation between lung tumor response and formation of 8-hydroxydeoxyguanosine (8-OHdG) in lung DNA of mice administered DEP by repeated intratracheal instillation. Repeated intratracheal instillation of DEP also induced the activity of cytochrome P-450 reductase in the lungs as a representative enzyme of superoxide generation, and two types of nitric oxide (NO) synthase, cNOS and iNOS, in the lungs. On the other hand, activities of CuZn-superoxide dismutase (SOD) and Mn-SOD antioxidant enzymes were depressed by the instillation of DEP. These results suggest that generation of superoxide, hydroxyI radical, and nitric oxide are increased in epithelial cells in airways, and that the increased superoxide and nitric oxide react very easily to produce peroxynitrite (ONOO(-)). The peroxynitrite also produce hydroxyI radical. The hydroxyl radical may play an important role in carcinogenesis by DEP.\",\n \"title\": \"Lung Carcinogenesis by Diesel Exhaust Particles and the Carcinogenic Mechanism Via Active Oxygens.\"\n },\n {\n \"docid\": \"10697096\",\n \"text\": \"BACKGROUND The purpose of this study was to test the hypothesis that vasodilator responses of porcine coronary resistance arteries are increased by exercise training. METHODS AND RESULTS Yucatan miniature swine were randomly divided into groups of exercise-trained (ET) and sedentary (SED) control pigs. ET pigs were placed on a progressive treadmill training program lasting 16 to 20 weeks, and SED pigs remained inactive during the same time period. Coronary resistance arteries 64 to 157 microns in diameter were isolated for in vitro evaluation of relaxation responses to the endothelium-independent dilators sodium nitroprusside (1 x 10(-10) to 1 x 10(-4) mol/L) and adenosine (1 x 10(-10) to 1 x 10(-5) mol/L) and to bradykinin (1 x 10(-13) to 3 x 10(-7) mol/L), an endothelium-dependent agent. Relaxation responses to adenosine and sodium nitroprusside were not altered by exercise training. Endothelium-dependent relaxation to bradykinin was enhanced in coronary resistance arteries from ET pigs (IC50: ET, 0.07 +/- 0.02 nmol/L; SED, 1.59 +/- 0.09 nmol/L). To determine whether prostanoids and/or the nitric oxide synthase pathway were involved in the ET-induced changes in bradykinin-induced vasodilation, responses to bradykinin were examined in coronary resistance arteries from both ET and SED pigs in the presence of indomethacin and in the presence of nitro-monomethyl L-arginine (L-NMMA). Both indomethacin and L-NMMA produced significant inhibition of the bradykinin-induced relaxation in vessels from both groups. Despite decreased bradykinin-induced relaxation after indomethacin, bradykinin-induced vasodilation was still enhanced in vessels from the ET group. L-NMMA caused greater inhibition of the bradykinin-induced relaxation in coronary resistance arteries from ET pigs relative to arteries from SED pigs and eliminated the training-induced enhancement of the bradykinin responses. CONCLUSIONS These results suggest that exercise training enhances bradykinin-induced vasodilation through increased endothelium-derived relaxing factor/nitric oxide production by the L-arginine/nitric oxide synthase pathway.\",\n \"title\": \"Vasodilator responses of coronary resistance arteries of exercise-trained pigs.\"\n },\n {\n \"docid\": \"8536018\",\n \"text\": \"Nitric oxide (NO) was identified as a key player in plant defence responses approximately 20 years ago and a large body of evidence has accumulated since then supporting its role as a signalling molecule. However, there are many discrepancies in current NO detection assays and the enzymatic pathways responsible for its synthesis have yet to be determined. This has provoked strong debates concerning the function of NO in plants, even questioning its existence in planta. Here we gather data obtained using the model pathosystem Arabidopsis/Pseudomonas, which confirms the production of NO during the hypersensitive response and supports is role as a trigger of hypersensitive cell death and a mediator of defence gene expression. Finally, we discuss potential sources of NO synthesis, focusing on the role of nitrite as major substrate for NO production during incompatible interactions.\",\n \"title\": \"Detection and function of nitric oxide during the hypersensitive response in Arabidopsis thaliana: where there's a will there's a way.\"\n },\n {\n \"docid\": \"21297708\",\n \"text\": \"1. Nitric oxide (NO) has been suggested as a gastrointestinal neurotransmitter, mediating the gastric receptive relaxation and the relaxation in the peristaltic reflex. The aim of the present study was to measure nerve-induced NO formation in vivo in the gastrointestinal tract. 2. Formation of the nitric oxide oxidation products nitrite and nitrate during vagal nerve stimulation were measured in the anaesthetized rabbit. Microdialysis probes were inserted into the wall of the stomach and proximal colon, and nitrite and nitrate in dialysate measured by capillary electrophoresis. 3. During bilateral vagal nerve stimulation there was an increase in nitrite and nitrate formation at the level of the stomach and in nitrite formation at the level of the colon. This increase was inhibited by intravenous administration of the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME 30 mg kg-1). Furthermore, L-NAME significantly increased nerve-induced gastric and colonic contractions, as well as spontaneous colonic contractions. 4. In summary, we present a new methodological procedure for quantification of small changes in nitric oxide formation in vivo. This study provides evidence that nitric oxide is released in the stomach and colonic wall during vagal nerve activity, at concentrations able to cause inhibition of smooth muscle contractions in vivo.\",\n \"title\": \"Nerve-induced release of nitric oxide in the rabbit gastrointestinal tract as measured by in vivo microdialysis.\"\n },\n {\n \"docid\": \"20381484\",\n \"text\": \"S-nitrosylation of proteins by nitric oxide is a major mode of signalling in cells. S-nitrosylation can mediate the regulation of a range of proteins, including prominent nuclear proteins, such as HDAC2 (ref. 2) and PARP1 (ref. 3). The high reactivity of the nitric oxide group with protein thiols, but the selective nature of nitrosylation within the cell, implies the existence of targeting mechanisms. Specificity of nitric oxide signalling is often achieved by the binding of nitric oxide synthase (NOS) to target proteins, either directly or through scaffolding proteins such as PSD-95 (ref. 5) and CAPON. As the three principal isoforms of NOS--neuronal NOS (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS)--are primarily non-nuclear, the mechanisms by which nuclear proteins are selectively nitrosylated have been elusive. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is physiologically nitrosylated at its Cys 150 residue. Nitrosylated GAPDH (SNO-GAPDH) binds to Siah1, which possesses a nuclear localization signal, and is transported to the nucleus. Here, we show that SNO-GAPDH physiologically transnitrosylates nuclear proteins, including the deacetylating enzyme sirtuin-1 (SIRT1), histone deacetylase-2 (HDAC2) and DNA-activated protein kinase (DNA-PK). Our findings reveal a novel mechanism for targeted nitrosylation of nuclear proteins and suggest that protein-protein transfer of nitric oxide groups may be a general mechanism in cellular signal transduction.\",\n \"title\": \"GAPDH Mediates Nitrosylation of Nuclear Proteins\"\n },\n {\n \"docid\": \"42873134\",\n \"text\": \"Type 1 and type 2 diabetes are characterized by progressive beta-cell failure. Apoptosis is probably the main form of beta-cell death in both forms of the disease. It has been suggested that the mechanisms leading to nutrient- and cytokine-induced beta-cell death in type 2 and type 1 diabetes, respectively, share the activation of a final common pathway involving interleukin (IL)-1beta, nuclear factor (NF)-kappaB, and Fas. We review herein the similarities and differences between the mechanisms of beta-cell death in type 1 and type 2 diabetes. In the insulitis lesion in type 1 diabetes, invading immune cells produce cytokines, such as IL-1beta, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma. IL-1beta and/or TNF-alpha plus IFN-gamma induce beta-cell apoptosis via the activation of beta-cell gene networks under the control of the transcription factors NF-kappaB and STAT-1. NF-kappaB activation leads to production of nitric oxide (NO) and chemokines and depletion of endoplasmic reticulum (ER) calcium. The execution of beta-cell death occurs through activation of mitogen-activated protein kinases, via triggering of ER stress and by the release of mitochondrial death signals. Chronic exposure to elevated levels of glucose and free fatty acids (FFAs) causes beta-cell dysfunction and may induce beta-cell apoptosis in type 2 diabetes. Exposure to high glucose has dual effects, triggering initially \\\"glucose hypersensitization\\\" and later apoptosis, via different mechanisms. High glucose, however, does not induce or activate IL-1beta, NF-kappaB, or inducible nitric oxide synthase in rat or human beta-cells in vitro or in vivo in Psammomys obesus. FFAs may cause beta-cell apoptosis via ER stress, which is NF-kappaB and NO independent. Thus, cytokines and nutrients trigger beta-cell death by fundamentally different mechanisms, namely an NF-kappaB-dependent mechanism that culminates in caspase-3 activation for cytokines and an NF-kappaB-independent mechanism for nutrients. This argues against a unifying hypothesis for the mechanisms of beta-cell death in type 1 and type 2 diabetes and suggests that different approaches will be required to prevent beta-cell death in type 1 and type 2 diabetes.\",\n \"title\": \"Mechanisms of pancreatic beta-cell death in type 1 and type 2 diabetes: many differences, few similarities.\"\n },\n {\n \"docid\": \"2533768\",\n \"text\": \"Clinical manifestations of diabetic nephropathy are an expression of diabetic microangiopathy. This review revisits the previously proposed Steno hypothesis and advances our hypothesis that development of endothelial cell dysfunction represents a common pathophysiological pathway of diabetic complications. Specifically, the ability of glucose to scavenge nitric oxide is proposed as the initiation phase of endothelial dysfunction. Gradual accumulation of advanced glycated end products and induction of plasminogen activator inhibitor-1, resulting in the decreased expression of endothelial nitric oxide synthase and reduced generation of nitric oxide, are proposed to be pathophysiologically critical for the maintenance phase of endothelial dysfunction. The proposed conceptual shift toward the role of endothelial dysfunction in diabetic complications may provide new strategies for their prevention.\",\n \"title\": \"Workshop: endothelial cell dysfunction leading to diabetic nephropathy : focus on nitric oxide.\"\n },\n {\n \"docid\": \"38944245\",\n \"text\": \"Lung Krüppel-like factor (LKLF/KLF2) is an endothelial transcription factor that is crucially involved in murine vasculogenesis and is specifically regulated by flow in vitro. We now show a relation to local flow variations in the adult human vasculature: decreased LKLF expression was noted at the aorta bifurcations to the iliac and carotid arteries, coinciding with neointima formation. The direct involvement of shear stress in the in vivo expression of LKLF was determined independently by in situ hybridization and laser microbeam microdissection/reverse transcriptase-polymerase chain reaction in a murine carotid artery collar model, in which a 4- to 30-fold induction of LKLF occurred at the high-shear sites. Dissection of the biomechanics of LKLF regulation in vitro demonstrated that steady flow and pulsatile flow induced basal LKLF expression 15- and 36-fold at shear stresses greater than approximately 5 dyne/cm2, whereas cyclic stretch had no effect. Prolonged LKLF induction in the absence of flow changed the expression of angiotensin-converting enzyme, endothelin-1, adrenomedullin, and endothelial nitric oxide synthase to levels similar to those observed under prolonged flow. LKLF repression by siRNA suppressed the flow response of endothelin-1, adrenomedullin, and endothelial nitric oxide synthase (P < 0.05). Thus, we demonstrate that endothelial LKLF is regulated by flow in vivo and is a transcriptional regulator of several endothelial genes that control vascular tone in response to flow.\",\n \"title\": \"Endothelial KLF2 links local arterial shear stress levels to the expression of vascular tone-regulating genes.\"\n },\n {\n \"docid\": \"46328296\",\n \"text\": \"Patients with essential hypertension exhibit blunted endothelium-dependent vasodilator responses, which may be largely attributable to reduced bioactivity of nitric oxide (NO). Therefore, we measured the end product of NO, nitrate plus nitrite (nitrogen oxide), and examined the relationship between the degree of hypertension and plasma nitrate plus nitrite levels in patients with essential hypertension. The combined plasma concentration of nitrate plus nitrite, end products of NO metabolism, was reduced in individuals with essential hypertension relative to that in control subjects (15.7+/-1.1 versus 22.8+/-1.4 mmol x L(-1), P<.001); individuals with borderline hypertension showed values that were intermediate between those of the other two groups (18.2+/-1.2 mmol x L(-1), P<.001). The plasma nitrogen oxide concentration showed significant inverse correlations with both systolic and diastolic blood pressures. The basal concentration of nitrogen oxide in the plasma was reduced, at least in the peripheral circulation, in individuals with essential hypertension.\",\n \"title\": \"Reduced plasma concentrations of nitrogen oxide in individuals with essential hypertension.\"\n },\n {\n \"docid\": \"7230315\",\n \"text\": \"The high-output pathway of nitric oxide production helps protect mice from infection by several pathogens, including Mycobacterium tuberculosis. However, based on studies of cells cultured from blood, it is controversial whether human mononuclear phagocytes can express the corresponding inducible nitric oxide synthase (iNOS;NOS2). The present study examined alveolar macrophages fixed directly after bronchopulmonary lavage. An average of 65% of the macrophages from 11 of 11 patients with untreated, culture-positive pulmonary tuberculosis reacted with an antibody documented herein to be monospecific for human NOS2. In contrast, a mean of 10% of bronchoalveolar lavage cells were positive from each of five clinically normal subjects. Tuberculosis patients' macrophages displayed diaphorase activity in the same proportion that they stained for NOS2, under assay conditions wherein the diaphorase reaction was strictly dependent on NOS2 expression. Bronchoalveolar lavage specimens also contained NOS2 mRNA. Thus, macrophages in the lungs of people with clinically active Mycobacterium tuberculosis infection often express catalytically competent NOS2.\",\n \"title\": \"Inducible nitric oxide synthase in pulmonary alveolar macrophages from patients with tuberculosis\"\n },\n {\n \"docid\": \"6580081\",\n \"text\": \"Ischemia-reperfusion injury is, at least in part, responsible for the morbidity associated with liver surgery under total vascular exclusion or after liver transplantation. The pathophysiology of hepatic ischemia-reperfusion includes a number of mechanisms that contribute to various degrees in the overall injury. Some of the topics discussed in this review include cellular mechanisms of injury, formation of pro- and anti-inflammatory mediators, expression of adhesion molecules, and the role of oxidant stress during the inflammatory response. Furthermore, the roles of nitric oxide in preventing microcirculatory disturbances and as a substrate for peroxynitrite formation are reviewed. In addition, emerging mechanisms of protection by ischemic preconditioning are discussed. On the basis of current knowledge, preconditioning or pharmacological interventions that mimic these effects have the greatest potential to improve clinical outcome in liver surgery involving ischemic stress and reperfusion.\",\n \"title\": \"Molecular mechanisms of hepatic ischemia-reperfusion injury and preconditioning.\"\n },\n {\n \"docid\": \"14711483\",\n \"text\": \"CONTEXT Vaso-occlusion is central to the painful crises and acute and chronic organ damage in sickle cell disease. Abnormal nitric oxide-dependent regulation of vascular tone, adhesion, platelet activation, and inflammation contributes to the pathophysiology of vaso-occlusion. Nitric oxide may have promise as a mechanism-of-disease-based therapy for treatment of vaso-occlusion. OBJECTIVE To explore the efficacy and safety of inhaled nitric oxide (INO) for treatment of vaso-occlusive crisis in pediatric patients. DESIGN Prospective, double-blind, placebo-controlled, randomized clinical trial with enrollment between September 1999 and October 2001. SETTING Urban, tertiary care children's hospital in the United States. PARTICIPANTS Twenty patients aged 10 to 21 years with sickle cell disease and severe acute vaso-occlusive crisis. INTERVENTION Patients were randomly assigned to receive INO (80 ppm with 21% final concentration of inspired oxygen; n = 10), or placebo (21% inspired oxygen; n = 10) for 4 hours. MAIN OUTCOME MEASURES Change in pain at 4 hours of inhalation compared with preinhalation pain, measured on a 10-cm visual analog scale (VAS); secondary outcome measures were pain over 6 hours, parenteral narcotic use over 24 hours, duration of hospitalization, blood pressure, oxygen saturation, and methemoglobin concentration. RESULTS Preinhalation VAS pain scores were similar in the INO and placebo groups (P =.80). The decrease in VAS pain scores at 4 hours was 2.0 cm in the INO group and 1.2 cm in the placebo group (P =.37). Repeated-measures analysis of variance for hourly pain scores showed a 1-cm/h greater reduction in the INO group than the placebo group (P =.02). Morphine use over 6 hours was significantly less in the INO group (mean cumulative use, 0.29 vs 0.44 mg/kg; P =.03) but was not different over 4 hours (0.26 vs 0.32 mg/kg; P =.21) or 24 hours (0.63 vs 0.91 mg/kg; P =.15). Duration of hospitalization was 78 and 100 hours in the INO and placebo groups, respectively (P =.19). No INO toxicity was observed. CONCLUSIONS Results of this exploratory study suggest that INO may be beneficial for acute vaso-occlusive crisis. These preliminary results warrant further investigation.\",\n \"title\": \"Preliminary assessment of inhaled nitric oxide for acute vaso-occlusive crisis in pediatric patients with sickle cell disease.\"\n },\n {\n \"docid\": \"12582729\",\n \"text\": \"BACKGROUND Upregulated by atheroprotective flow, the transcription factor Krüppel-like factor 2 (KLF2) is crucial for maintaining endothelial function. MicroRNAs (miRNAs) are noncoding small RNAs that regulate gene expression at the posttranscriptional level. We examined the role of miRNAs, particularly miR-92a, in the atheroprotective flow-regulated KLF2. METHODS AND RESULTS Dicer knockdown increased the level of KLF2 mRNA in human umbilical vein endothelial cells, suggesting that KLF2 is regulated by miRNA. In silico analysis predicted that miR-92a could bind to the 3' untranslated region of KLF2 mRNA. Overexpression of miR-92a decreased the expression of KLF2 and the KLF2-regulated endothelial nitric oxide synthase and thrombomodulin at mRNA and protein levels. A complementary finding is that miR-92a inhibitor increased the mRNA and protein expression of KLF2, endothelial nitric oxide synthase, and thrombomodulin. Subsequent studies revealed that atheroprotective laminar flow downregulated the level of miR-92a precursor to induce KLF2, and the level of this flow-induced KLF2 was reduced by miR-92a precursor. Furthermore, miR-92a level was lower in human umbilical vein endothelial cells exposed to the atheroprotective pulsatile shear flow than under atheroprone oscillatory shear flow. Anti-Ago1/2 immunoprecipitation coupled with real-time polymerase chain reaction revealed that pulsatile shear flow decreased the functional targeting of miR-92a precursor/KLF2 mRNA in human umbilical vein endothelial cells. Consistent with these findings, mouse carotid arteries receiving miR-92a precursor exhibited impaired vasodilatory response to flow. CONCLUSIONS Atheroprotective flow patterns decrease the level of miR-92a, which in turn increases KLF2 expression to maintain endothelial homeostasis.\",\n \"title\": \"Flow-Dependent Regulation of Kruppel-Like Factor 2 Is Mediated by MicroRNA-92a.\"\n },\n {\n \"docid\": \"15561961\",\n \"text\": \"Hypercholesterolemia is associated with impairments in endothelium-dependent vascular relaxations. Paradoxically, endothelial production of nitrogen oxides is increased in early stages of hypercholesterolemia. Prior work has shown that oxidized low density lipoprotein (LDL) has both stimulatory and inhibitory effects on endothelial nitric oxide synthase expression (eNOS) and has focused on lysophosphatidyl choline (LPC) as a component of oxidized LDL which may modulate this effect. Another biologically active component of oxidized LDL is 13-hydroperoxyoctadecadienoic acid (13-HPODE), an oxidized form of linoleic acid. The purpose of this study was to determine the effect of HPODE on the expression of eNOS in bovine aortic endothelial cells (BAECs). Twenty four hour treatment of endothelial cells with HPODE caused a dose-dependent increase in eNOS mRNA levels as assessed by Northern analysis. The time response studies show that HPODE treatment significantly increased eNOS mRNA levels at 12 and 24 h. Concomitant with the increase in eNOS mRNA levels, 20 microM HPODE treatment significantly increased eNOS protein content and enzyme activity. Nuclear run-on studies indicated that the rate of transcription of eNOS gene was significantly elevated 4 h after HPODE treatment when compared to control cultures. Also, actinomycin D studies demonstrated that the half-life of eNOS mRNA was increased from 6 h to 12 h by HPODE treatment. Thus, HPODE-induced up-regulation of eNOS expression is mediated by both transcriptional and posttranscriptional mechanisms. These observations suggest that endothelial cells may attempt to compensate for oxidative injury by increasing expression of eNOS in early stages of hypercholesterolemia.\",\n \"title\": \"expression by oxidized linoleic\"\n },\n {\n \"docid\": \"28207326\",\n \"text\": \"Vascular endothelial growth factor-A (VEGF-A) is a protein secreted by podocytes that is necessary for survival of endothelial cells, podocytes, and mesangial cells. VEGF-A regulates slit-diaphragm signaling and podocyte shape via VEGF-receptor 2-nephrin-nck-actin interactions. Chronic hyperglycemia-induced excess podocyte VEGF-A and low endothelial nitric oxide drive the development and the progression of diabetic nephropathy. The abnormal cross-talk between VEGF-A and nitric oxide pathways is fueled by the diabetic milieu, resulting in increased oxidative stress. Recent findings on these pathogenic molecular mechanisms provide new potential targets for therapy for diabetic renal disease.\",\n \"title\": \"VEGF and podocytes in diabetic nephropathy.\"\n },\n {\n \"docid\": \"26658659\",\n \"text\": \"Hydrogen sulfide (H(2)S) was recently discovered to be synthesized in mammalian tissues by several different enzymes. Numerous studies have shown that H(2)S has vasodilator and antihypertensive effects in the cardiovascular system. However, intracellular mechanisms of the H(2)S-induced vasodilation and its interactions with other endothelium-derived relaxing factors, such as nitric oxide (NO), remain unclear. We investigated whether H(2)S directly regulates endothelial NO synthase (eNOS) activity and NO production in endothelial cells. NaHS, a H(2)S donor, dose-dependently increased NO production in cultured endothelial cells. This effect was abolished by a calcium chelator (BAPTA-AM), but not by the absence of extracellular calcium. The NaHS-induced NO production was partially blocked by inhibitors of ryanodine receptor (dantrolene) or inositol 1,4,5-triphosphate receptor (xestospongin C). NaHS significantly increased intracellular calcium concentrations, and this effect was attenuated by dantrolene or xestospongin C. NaHS induced phosphorylation of eNOS at the activating phosphoserine residue 1179. The NaHS-induced eNOS phosphorylation and NO production were not affected by a PI3K/Akt inhibitor (wortmannin). The data of this study suggest that H(2)S directly acts on endothelial cells to induce eNOS activation and NO production by releasing calcium from the intracellular store in endoplasmic reticulum, which may explain one of mechanisms of its vasodilator function.\",\n \"title\": \"Hydrogen sulfide increases nitric oxide production with calcium-dependent activation of endothelial nitric oxide synthase in endothelial cells.\"\n },\n {\n \"docid\": \"5785219\",\n \"text\": \"Nitric oxide (NO) is a product of L-arginine metabolism that suppresses cellular oxidative metabolism through the inhibition of tricarboxylic acid cycle and electron transport chain enzymes. The impact of NO synthase (NOS) activity on specific pathways of glucose metabolism in freshly harvested and overnight-cultured rat resident peritoneal macrophages, at rest and after stimulation with zymosan, was investigated using radiolabeled glucose. NOS activity was modulated through the L-arginine concentration in culture media and the use of its specific inhibitor, NG-monomethyl-L-arginine, and quantitated using radiolabeled L-arginine. Results demonstrated that NOS activity was associated with increased glucose disappearance, glycolysis, and hexose monophosphate shunt activity and, in line with the known inhibition of oxidative metabolism associated with the production of NO, with a decrease in the flux of glucose and butyrate carbon through the tricarboxylic acid cycle. In addition, the relative increase in glucose utilization that follows zymosan stimulation was enhanced by treatments that suppressed NOS activity. These results demonstrate that the characteristics of glucose metabolism by macrophages are, to a significant extent, determined by products of NOS.\",\n \"title\": \"Modulation of glucose metabolism in macrophages by products of nitric oxide synthase.\"\n },\n {\n \"docid\": \"6923795\",\n \"text\": \"Cytochrome P450 (P450)-dependent metabolites of arachidonic acid, the epoxyeicosatrienoic acids (EETs), are proposed to be endothelium-derived hyperpolarizing factors (EDHF) that affect vascular tone; however, the effects of EDHF on endothelial-derived nitric oxide biosynthesis remain unknown. We examined the regulation of endothelial nitric-oxide synthase (eNOS) by EDHF and investigated the relevant signaling pathways involved. The P450 epoxygenases CYP102 F87V mutant, CYP2C11-CYPOR, and CYP2J2 were transfected into cultured bovine aortic endothelial cells, and the effects of endogenously formed or exogenously applied EETs on eNOS expression and activity were assessed. Transfection with the P450 epoxygenases led to increased eNOS protein expression, an effect that was attenuated by cotreatment with the P450 inhibitor 17-ODYA. Northern analysis demonstrated that P450 transfection led to increased eNOS mRNA levels consistent with an effect at the pretranslational level. P450 epoxygenase transfection resulted in increased eNOS activity as measured by the conversion of L-arginine to L-citrulline. Addition of synthetic EETs (50-200 nM) to the culture media also increased eNOS expression and activity. Treatment with mitogen-activated protein kinase (MAPK), MAPK kinase, and protein kinase C inhibitors apigenin, 2'-amino-3'-methoxyflavone (PD98059), and 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7), respectively, significantly inhibited the effects of P450 transfection on eNOS expression. Overexpression of P450 epoxygenases or addition of synthetic EETs increased Thr495 phosphorylation of eNOS, an effect that was inhibited by both apigenin and PD98059. Overexpression of P450 epoxygenases in rats resulted in increased aortic eNOS expression, providing direct evidence that EDHF can influence vascular eNOS levels in vivo. Based on this data, we conclude that EDHF up-regulates eNOS via activation of MAPK and protein kinase C signaling pathways.\",\n \"title\": \"Up-regulation of endothelial nitric-oxide synthase by endothelium-derived hyperpolarizing factor involves mitogen-activated protein kinase and protein kinase C signaling pathways.\"\n },\n {\n \"docid\": \"24705390\",\n \"text\": \"BACKGROUND & AIMS Helicobacter pylori is an important etiologic factor in the development of gastric cancer. The aim of this study was to analyze the role of H. pylori infections in the induction of mutagenic events in gastric epithelial cells. The effect of a high-salt diet as a genotoxic risk factor was also investigated. METHODS Big Blue transgenic male mice (C57Bl/6) were inoculated with H. pylori (strain SS1) or Helicobacter felis (strain CS1) for 6 and 12 months. The frequency and spectrum of mutations at the stomach level were assessed. Inflammatory host response and inducible nitric oxide synthase (iNOS) expression by reverse-transcription polymerase chain reaction and immunohistochemistry analysis were also performed. RESULTS After 6 months, the gastric mutant frequency was 4-fold and 1.7-fold higher in mice infected with H. pylori and H. felis, respectively, than in uninfected mice. It was associated with a high frequency of transversions (AT --> CG and GC --> TA) known to result from oxidative damages. The Helicobacter-infected mice exhibited severe gastritis and a high level of iNOS messenger RNA expression. Hyperplasia developed 12 months after inoculation, and both the mutagenic effects and iNOS expression decreased in H. pylori- and H. felis-infected mice. No synergistic effects of a high-salt diet and Helicobacter infection were observed regarding the frequency of gastric mutation. CONCLUSIONS A direct gastric mutagenic effect due to H. pylori infection in the Big Blue transgenic mouse model has been shown 6 months after inoculation. This genotoxicity can be attributable to oxidative DNA damage involving the inflammatory host response.\",\n \"title\": \"Chronic Helicobacter pylori infections induce gastric mutations in mice.\"\n },\n {\n \"docid\": \"22995164\",\n \"text\": \"Nitrosoglutathione [(GSNO), 500 nmol/l] relaxed the norepinephrine precontracted rat aortic rings. The relaxation effect was pronouncedly enhanced by H2S- and HS−-donor NaHS (30 μmol/l) at 7.5 pH but not at 6.3 pH. To study molecular mechanism of this effect, we investigated whether NaHS can release NO from NO donors. Using an electron paramagnetic resonance spectroscopy method of spin trap and by measuring the NO oxidation product, which is nitrite, by the Griess reaction, we report that NaHS released NO from nitrosothiols, namely from GSNO, S-nitroso-N-acetyl-dl-penicillamine (SNAP), from metal nitrosyl complex nitroprusside (SNP) and from rat brain homogenate and murine L1210 leukaemia cells. From the observation that the releasing effect was more pronounced at 8.0 pH than 6.0 pH, we suppose that HS−, rather than H2S, is responsible for the NO-releasing effect. Since in mammals, H2S and HS− are produced endogenously, we assume that their effect to release NO from nitrosothiols and from metal nitrosyl complexes are responsible for some of their biological activities and that this mechanism may be involved in S-nitrosothiol-signalling reactions.\",\n \"title\": \"H2S and HS− donor NaHS releases nitric oxide from nitrosothiols, metal nitrosyl complex, brain homogenate and murine L1210 leukaemia cells\"\n },\n {\n \"docid\": \"32985041\",\n \"text\": \"Nitric oxide (NO) has been linked to numerous physiological and pathophysiological events that are not readily explained by the well established effects of NO on soluble guanylyl cyclase. Exogenous NO S-nitrosylates cysteine residues in proteins, but whether this is an important function of endogenous NO is unclear. Here, using a new proteomic approach, we identify a population of proteins that are endogenously S-nitrosylated, and demonstrate the loss of this modification in mice harbouring a genomic deletion of neuronal NO synthase (nNOS). Targets of NO include metabolic, structural and signalling proteins that may be effectors for neuronally generated NO. These findings establish protein S-nitrosylation as a physiological signalling mechanism for nNOS.\",\n \"title\": \"Protein S-nitrosylation: a physiological signal for neuronal nitric oxide\"\n },\n {\n \"docid\": \"79447\",\n \"text\": \"OBJECTIVE The purpose of this study was to characterize the relationship between adipose tissue phenotype and depot-specific microvascular function in fat. METHODS AND RESULTS In 30 obese subjects (age 42±11 years, body mass index 46±11 kg/m(2)) undergoing bariatric surgery, we intraoperatively collected visceral and subcutaneous adipose tissue and characterized depot-specific adipose phenotypes. We assessed vasomotor function of the adipose microvasculature using videomicroscopy of small arterioles (75-250 μm) isolated from different fat compartments. Endothelium-dependent, acetylcholine-mediated vasodilation was severely impaired in visceral arterioles, compared to the subcutaneous depot (P<0.001 by ANOVA). Nonendothelium dependent responses to papaverine and nitroprusside were similar. Endothelial nitric oxide synthase inhibition with N(ω)-nitro-l-arginine methyl ester reduced subcutaneous vasodilation but had no effect on severely blunted visceral arteriolar responses. Visceral fat exhibited greater expression of proinflammatory, oxidative stress-related, hypoxia-induced, and proangiogenic genes; increased activated macrophage populations; and had a higher capacity for cytokine production ex vivo. CONCLUSIONS Our findings provide clinical evidence that the visceral microenvironment may be intrinsically toxic to arterial health providing a potential mechanism by which visceral adiposity burden is linked to atherosclerotic vascular disease. Our findings also support the evolving concept that both adipose tissue quality and quantity may play significant roles in shaping cardiovascular phenotypes in human obesity.\",\n \"title\": \"Arteriolar function in visceral adipose tissue is impaired in human obesity.\"\n },\n {\n \"docid\": \"11181416\",\n \"text\": \"Because arginase hydrolyzes arginine to produce ornithine and urea, it has the potential to regulate nitric oxide (NO) and polyamine synthesis. We tested whether expression of the cytosolic isoform of arginase (arginase I) was limiting for NO or polyamine production by activated RAW 264.7 macrophage cells. RAW 264.7 cells, stably transfected to overexpress arginase I or beta-galactosidase, were treated with interferon-gamma to induce type 2 NO synthase or with lipopolysaccharide or 8-bromo-cAMP (8-BrcAMP) to induce ornithine decarboxylase. Overexpression of arginase I had no effect on NO synthesis. In contrast, cells overexpressing arginase I produced twice as much putrescine after activation than did cells expressing beta-galactosidase. Cells overexpressing arginase I also produced more spermidine after treatment with 8-BrcAMP than did cells expressing beta-galactosidase. Thus endogenous levels of arginase I are limiting for polyamine synthesis, but not for NO synthesis, by activated macrophage cells. This study also demonstrates that it is possible to alter arginase I levels sufficiently to affect polyamine synthesis without affecting induced NO synthesis.\",\n \"title\": \"Arginase I: a limiting factor for nitric oxide and polyamine synthesis by activated macrophages?\"\n },\n {\n \"docid\": \"43048059\",\n \"text\": \"AIMS The present study aims to investigate the interaction between nitric oxide (NO) and hydrogen sulfide (H(2)S), the two important gaseous mediators in rat hearts. METHODS AND RESULTS Intracellular calcium in isolated cardiomyocytes was measured with a spectrofluorometric method using Fura-2. Myocyte contractility was measured with a video edge system. NaHS (50 µM, an H(2)S donor) had no significant effect on the resting calcium level, electrically induced (EI) calcium transients, and cell contractility in ventricular myocytes. Stimulating endogenous NO production with l-arginine or exogenous application of NO donors [sodium nitroprusside (SNP) and 2-(N,N-diethylamino)-diazenolate-2-oxide] decreased myocyte twitch amplitudes accompanied by slower velocities of both cell contraction and relaxation. Surprisingly, NaHS reversed the negative inotropic and lusitropic effects of the above three NO-increasing agents. In addition, the mixture of SNP + NaHS increased, whereas SNP alone decreased, the resting calcium level and the amplitudes of EI calcium transients. Angeli's salt, a nitroxyl anion (HNO) donor, mimicked the effect of SNP + NaHS on calcium handling and myocyte contractility. Three thiols, N-acetyl-cysteine, l-cysteine, and glutathione, abolished the effects of HNO and SNP + NaHS on myocyte contraction. Neither Rp-cAMP [a protein kinase A (PKA) inhibitor] nor Rp-cGMP [a protein kinase G (PKG) inhibitor] affected the effects of SNP + NaHS, suggesting a cAMP/PKA- or cGMP/PKG-independent mechanism. CONCLUSION H(2)S may interact with NO to form a thiol sensitive molecule (probably HNO) which produces positive inotropic and lusitropic effects. Our findings may shed light on the interaction of NO and H(2)S and provide new clues to treat cardiovascular diseases.\",\n \"title\": \"Hydrogen sulfide interacts with nitric oxide in the heart: possible involvement of nitroxyl.\"\n },\n {\n \"docid\": \"23513718\",\n \"text\": \"Responses of cerebral blood vessels to nitric oxide (NO) are mediated by soluble guanylate cyclase (sGC)-dependent and potentially by sGC-independent mechanisms. One sGC-independent mechanism by which NO may produce vasodilatation is inhibition of formation of a vasoconstrictor metabolite produced through the cytochrome P450 pathway. In these experiments, we examined the hypothesis that dilatation of cerebral microvessels in response to NO is dependent on activation of sGC. Diameters of cerebral arterioles (baseline diameter=94+/-5 micrometers, mean+/-S.E.) were measured using a closed cranial window in anesthetized rabbits. Under control conditions, YC-1 [3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole], an NO-independent activator of sGC, produced vasodilation that was blocked by ODQ (1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one)(10 microM), an inhibitor of sGC. These findings indicate that sGC is functionally important in cerebral arterioles. In addition, acetylcholine (which stimulates endogenous production of NO by endothelium) produced dilatation of cerebral arterioles that was inhibited by ODQ. For example, 1 microM acetylcholine dilated cerebral arterioles by 34+/-7 and 5+/-1% in the absence and presence of ODQ (10 microM), respectively. Increases in arteriolar diameter in response to sodium nitroprusside (1 microM, an NO donor) were inhibited by approximately 80% by ODQ, but were not affected by 17-ODYA (10 microM) or clotrimazole (10 microM), inhibitors of the cytochrome P450 pathway. Thus, dilatation of the cerebral microcirculation in response to exogenously applied and endogenously produced NO is dependent, in large part, on activation of sGC.\",\n \"title\": \"Role of soluble guanylate cyclase in dilator responses of the cerebral microcirculation.\"\n }\n]"}}}],"truncated":false,"partial":false},"paginationData":{"pageIndex":1,"numItemsPerPage":100,"numTotalItems":3240,"offset":100,"length":100}},"jwt":"eyJhbGciOiJFZERTQSJ9.eyJyZWFkIjp0cnVlLCJwZXJtaXNzaW9ucyI6eyJyZXBvLmNvbnRlbnQucmVhZCI6dHJ1ZX0sImlhdCI6MTc1NzQwOTEyOCwic3ViIjoiL2RhdGFzZXRzL3Nza3RvcmEvbmZjb3JwdXMtc2NpZmFjdC1maXFhLWZldmVyLWhvdHBvdHFhLWNvbWJpbmUtNjQ4IiwiZXhwIjoxNzU3NDEyNzI4LCJpc3MiOiJodHRwczovL2h1Z2dpbmdmYWNlLmNvIn0.7IfOQRsYnv46J05OHXzkkZoR5SupPevs4lWPaPzbotjeLdf5k6xYVbKasNzYjWQ90OS1fGm4K2csl6NSwe_ABw","displayUrls":true},"discussionsStats":{"closed":0,"open":1,"total":1},"fullWidth":true,"hasGatedAccess":true,"hasFullAccess":true,"isEmbedded":false,"savedQueries":{"community":[],"user":[]}}">
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PLAIN-1769
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organic foods
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[
{
"docid": "MED-4089",
"text": "Studies have shown an inverse relationship between the consumption of apples and the risk of several cancers. The peels of apple, which have been shown to possess exceptionally high concentrations of antioxidants, are often discarded. In this study, we evaluated the antiproliferative effects of apple peel extract (APE) in variety of cancer cell types. Our data demonstrated that APE, obtained from organic Gala apples, imparted significant reduction in the viability of a variety of cancer cell lines. Further, our data showed a significant decrease in growth and clonogenic survival of human prostate carcinoma CWR22Rnu1 and DU145 cells and breast carcinoma Mcf-7 and Mcf-7:Her18 cells. Also, the antiproliferative effects of APE were found to be accompanied by a G0-G1 phase arrest of prostate and breast cancer cells. Furthermore, APE treatment resulted in a marked concentration-dependent decrease in the protein levels of proliferative cell nuclear antigen, a marker for proliferation. In addition, APE treatment resulted in a marked increase in maspin, a tumor suppressor protein that negatively regulates cell invasion, metastasis, and angiogenesis. Our data suggested that APE possesses strong antiproliferative effects against cancer cells, and apple peels should not be discarded from the diet. Detailed mechanistic studies, especially in appropriate in vivo animal models, are needed to further examine the antiproliferative and preventive effects of APE against cancer.",
"title": "Antiproliferative effects of apple peel extract against cancer cells."
},
{
"docid": "MED-2748",
"text": "The consumption of fresh produce is frequently associated with outbreaks of human norovirus (hNoV) disease. To prevent the contamination of fresh produce with hNoV, knowledge of the possible introduction sources of the viruses, such as water, is needed to be able to implement appropriate and efficient preventive measures. Contaminated water used to reconstitute pesticides could be a relevant source of infectious hNoV, determined by the initial level of virus contamination and the persistence of these viruses in reconstituted pesticides. We studied the persistence of hNoV GI.4, hNoV GII.4 and murine norovirus (MNV-1), the only culturable norovirus, in eight different pesticides after 0 and 2h. Virus concentrations were determined by reverse transcriptase PCR, and infectivity of MNV-1 was determined by endpoint dilutions followed by maximum likelihood estimations. MNV-1 was found to remain infectious in seven of the eight tested pesticides at the highest concentration applied in practice. In the presence of the insecticide Vertimec, MNV-1 infectivity decreased rapidly with a 1.9 log(10)-unit reduction at timepoint T(0). Also, the concentration of NoV GI.4 RNA decreased considerably with a 1.7 log(10)-unit reduction; whereas the detected PCR fragment of hNoV GII.4 remained stable. Assuming a similar persistence of infectious MNV-1 and hNoV we can conclude that water containing hNoV used to dilute pesticides may be an important source of infectious hNoV in fresh produce chains. The application of pesticides may therefore not only be a chemical hazard, but also a microbiological hazard for public health. The inclusion of antiviral substances in reconstituted pesticides may be appropriate to reduce the virological health risk posed by the application of pesticides. Copyright © 2012 Elsevier B.V. All rights reserved.",
"title": "Persistence of human norovirus in reconstituted pesticides--pesticide application as a possible source of viruses in fresh produce chains."
},
{
"docid": "MED-1588",
"text": "Multiple pregnancy rates remain high after assisted conception because of a misconceived assumption that transferring three or more embryos will maximize pregnancy rates. Maternal morbidity is sevenfold greater in multiple pregnancies than in singletons, perinatal mortality rates are fourfold higher for twins and sixfold higher for triplets, while cerebral palsy rates are 1-1.5% in twin and 7-8% in triplet pregnancies. Therefore, multiple pregnancies must be considered a serious adverse outcome of assisted reproductive techniques. Primary prevention of multiple pregnancies is the solution. The overwhelming evidence presented in this chapter demonstrates that limiting the embryo transfer in in vitro fertilization to two embryos would significantly reduce adverse maternal and perinatal outcomes by reducing the incidence of high order multiple pregnancies without reducing take-home-baby rates. Secondary prevention by multifetal pregnancy reduction is effective, but not acceptable to all patients. New developments in blastocyst culture, single embryo transfer, embryo cryopreservation and pre-implantation aneuploidy exclusion, should allow improvements in pregnancy rates without increasing multiple pregnancies.",
"title": "Reducing the incidence of twins and triplets."
},
{
"docid": "MED-1733",
"text": "INTRODUCTION: Glyphosate-surfactant herbicide (GlySH) is widely used as a non-selective herbicide. Most intoxicated cases are from ingestion, inhalation, and skin exposure. Intramuscular injection of GlySH has never been reported. We present a case of GlySH intoxication via intramuscular injection. CASE REPORT: A 42-year-old woman came to the emergency department complaining of painful swelling of left upper limb for 12 h. She had performed an intramuscular injection of 6 mL of GlySH over the lateral aspect of the left elbow 15 h previously. Physical examination disclosed painful swelling over left distal arm, elbow, and forearm with three needle punctures. CT scan revealed ill-defined areas of heterogeneous high density with marked swelling at subcutaneous tissue over posterior aspect of the elbow. DISCUSSION: The mechanism of toxicity of GlySH is complicated and surfactant was thought to play an important role in GlySH intoxication. Intramuscular GlySH poisoning is different from oral GlySH intoxication. Care should be taken when monitoring acute rhabdomyolysis and compartment syndrome, which may develop rapidly and contribute to the surfactant component of glyphosate formulation.",
"title": "Rhabdomyolysis from an intramuscular injection of glyphosate-surfactant herbicide."
},
{
"docid": "MED-2644",
"text": "Alkylphenols are widely used as plastic additives and surfactants. We report the identification of an alkylphenol, nonylphenol, as an estrogenic substance released from plastic centrifuge tubes. This compound was extracted with methanol, purified by flash chromatography and reverse-phase high performance liquid chromatography, and identified by gas chromatography-mass spectrometry. Nonylphenol induced both cell proliferation and progesterone receptor in human estrogen-sensitive MCF7 breast tumor cells. Nonylphenol also triggered mitotic activity in rat endometrium; this result confirms the reliability of the MCF7 cell proliferation bioassay. The estrogenic properties of alkylphenols, specifically nonylphenols, indicate that the use of plasticware containing these chemicals in experimental and diagnostic tests may lead to spurious results, and these compounds as well as alkylphenol polyethoxylates may also be potentially harmful to exposed humans and the environment at large.",
"title": "p-Nonyl-phenol: an estrogenic xenobiotic released from \"modified\" polystyrene."
},
{
"docid": "MED-2884",
"text": "Two carotenoids found in egg yolk, lutein and zeaxanthin, accumulate in the macular retina where they may reduce photostress. Increases in serum lutein and zeaxanthin were observed in previous egg interventions, but no study measured macular carotenoids. The objective of this project was to determine whether increased consumption of eggs would increase retinal lutein and zeaxanthin, or macular pigment. Twenty-four females, between 24 and 59 y, were assigned to a pill treatment (PILL) or 1 of 2 egg treatments for 12 wk. Individuals in the PILL treatment consumed 1 sugar-filled capsule/d. Individuals in the egg treatments consumed 6 eggs/wk, containing either 331 microg (EGG 1) or 964 microg (EGG 2) of lutein and zeaxanthin/yolk. Serum cholesterol, serum carotenoids, and macular pigment OD (MPOD) were measured at baseline and after 4, 8, and 12 wk of intervention. Serum cholesterol concentrations did not change in either egg treatment group, but total cholesterol (P = 0.04) and triglycerides (P = 0.02) increased in the PILL group. Serum zeaxanthin, but not serum lutein, increased in both the EGG 1 (P = 0.04) and EGG 2 (P = 0.01) groups. Likewise, MPOD increased in both the EGG 1 (P = 0.001) and EGG 2 (P = 0.049) groups. Although the aggregate concentration of carotenoid in 1 egg yolk may be modest relative to other sources, such as spinach, their bioavailability to the retina appears to be high. Increasing egg consumption to 6 eggs/wk may be an effective method to increase MPOD.",
"title": "A 12-wk egg intervention increases serum zeaxanthin and macular pigment optical density in women."
},
{
"docid": "MED-1158",
"text": "The efficiencies of acidic solutions (radish, citric acid, ascorbic acid, acetic acid and hydrogen peroxide), neutral solutions (sodium chloride) and alkaline solution (sodium carbonate) as well as tap water in the elimination of organochlorine and organophosphorus pesticides from naturally contaminated potatoes were examined. The results indicated that acidic solutions were more effective than neutral and alkaline solutions in the elimination of the organochlorine compounds under investigation, Radish solutions eliminated pesticides completely, except o,p'-DDE (73.1% loss), followed by citric and ascorbic acid solutions. On the other hand, organophosphorus pesticides (pirimphos methyl, malathion and profenofos) were eliminated more by acidic, neutral and alkaline solutions than by organochlorines. The percentage of removal ranged from 98.5 to 100% for pirimphos methyl, 87.9 to 100% for malathion and 100% for profenofos.",
"title": "Behaviour of some organophosphorus and organochlorine pesticides in potatoes during soaking in different solutions."
},
{
"docid": "MED-2774",
"text": "Concern has been expressed about the fact that cows' milk contains estrogens and could stimulate the growth of hormone-sensitive tumors. In this study, organic cows' milk and two commercial substitutes were digested in vitro and tested for their effects on the growth of cultures of prostate and breast cancer cells. Cows' milk stimulated the growth of LNCaP prostate cancer cells in each of 14 separate experiments, producing an average increase in growth rate of over 30%. In contrast, almond milk suppressed the growth of these cells by over 30%. Neither cows' milk nor almond milk affected the growth of MCF-7 breast cancer cells or AsPC-1 pancreatic cancer cells significantly. Soy milk increased the growth rate of the breast cancer cells. These data indicate that prostate and breast cancer patients should be cautioned about the possible promotional effects of commercial dairy products and their substitutes.",
"title": "Milk stimulates growth of prostate cancer cells in culture."
},
{
"docid": "MED-1744",
"text": "Eighty percent of (commercial) genetically engineered seeds (GES) are designed only to resist herbicides. Letting farmers use more chemicals, they cut labor costs. But developing nations say GES cause food shortages, unemployment, resistant weeds, and extinction of native cultivars when \"volunteers\" drift nearby. While GES patents are reasonable, this paper argues many patent policies are not. The paper surveys GE technology, outlines John Locke's classic account of property rights, and argues that current patent policies must be revised to take account of Lockean ethical constraints. After answering a key objection, it provides concrete suggestions for implementing its ethical conclusions.",
"title": "Property rights and genetic engineering: developing nations at risk."
},
{
"docid": "MED-1167",
"text": "Along with the wide use of pesticides in the world, the concerns over their health impacts are rapidly growing. There is a huge body of evidence on the relation between exposure to pesticides and elevated rate of chronic diseases such as different types of cancers, diabetes, neurodegenerative disorders like Parkinson, Alzheimer, and amyotrophic lateral sclerosis (ALS), birth defects, and reproductive disorders. There is also circumstantial evidence on the association of exposure to pesticides with some other chronic diseases like respiratory problems, particularly asthma and chronic obstructive pulmonary disease (COPD), cardiovascular disease such as atherosclerosis and coronary artery disease, chronic nephropathies, autoimmune diseases like systemic lupus erythematous and rheumatoid arthritis, chronic fatigue syndrome, and aging. The common feature of chronic disorders is a disturbance in cellular homeostasis, which can be induced via pesticides' primary action like perturbation of ion channels, enzymes, receptors, etc., or can as well be mediated via pathways other than the main mechanism. In this review, we present the highlighted evidence on the association of pesticide's exposure with the incidence of chronic diseases and introduce genetic damages, epigenetic modifications, endocrine disruption, mitochondrial dysfunction, oxidative stress, endoplasmic reticulum stress and unfolded protein response (UPR), impairment of ubiquitin proteasome system, and defective autophagy as the effective mechanisms of action. Copyright © 2013 Elsevier Inc. All rights reserved.",
"title": "Pesticides and human chronic diseases: evidences, mechanisms, and perspectives."
},
{
"docid": "MED-1729",
"text": "We previously demonstrated that the frequency of birth defects among children of residents of the Red River Valley (RRV), Minnesota, USA, was significantly higher than in other major agricultural regions of the state during the years 1989-1991, with children born to male pesticide applicators having the highest risk. The present, smaller cross-sectional study of 695 families and 1,532 children, conducted during 1997-1998, provides a more detailed examination of reproductive health outcomes in farm families ascertained from parent-reported birth defects. In the present study, in the first year of life, the birth defect rate was 31.3 births per 1,000, with 83% of the total reported birth defects confirmed by medical records. Inclusion of children identified with birth or developmental disorders within the first 3 years of life and later led to a rate of 47.0 per 1,000 (72 children from 1,532 live births). Conceptions in spring resulted in significantly more children with birth defects than found in any other season (7.6 vs. 3.7%). Twelve families had more than one child with a birth defect (n = 28 children). Forty-two percent of the children from families with recurrent birth defects were conceived in spring, a significantly higher rate than that for any other season. Three families in the kinships defined contributed a first-degree relative other than a sibling with the same or similar birth defect, consistent with a Mendelian inheritance pattern. The remaining nine families did not follow a Mendelian inheritance pattern. The sex ratio of children with birth defects born to applicator families shows a male predominance (1.75 to 1) across specific pesticide class use and exposure categories exclusive of fungicides. In the fungicide exposure category, normal female births significantly exceed male births (1.25 to 1). Similarly, the proportion of male to female children with birth defects is significantly lower (0.57 to 1; p = 0.02). Adverse neurologic and neurobehavioral developmental effects clustered among the children born to applicators of the fumigant phosphine (odds ratio [OR] = 2.48; confidence interval [CI], 1.2-5.1). Use of the herbicide glyphosate yielded an OR of 3.6 (CI, 1.3-9.6) in the neurobehavioral category. Finally, these studies point out that (a) herbicides applied in the spring may be a factor in the birth defects observed and (b) fungicides can be a significant factor in the determination of sex of the children of the families of the RRV. Thus, two distinct classes of pesticides seem to have adverse effects on different reproductive outcomes. Biologically based confirmatory studies are needed.",
"title": "Birth defects, season of conception, and sex of children born to pesticide applicators living in the Red River Valley of Minnesota, USA."
},
{
"docid": "MED-2652",
"text": "The exposure to some chemicals can lead to hormone disrupting effects. Presently, much attention is focused on so-called xeno-estrogens, synthetic compounds that interact with hormone receptors causing a number of reactions that eventually lead to effects related to reproduction and development. The current study was initiated to investigate the presence of a number of such compounds in precipitation as a follow-up on a previous study in which pesticide concentrations in air and precipitation were determined. Rainwater samples were collected at about 50 locations in The Netherlands in a four week period. The samples were analysed for bisphenol-A, alkylphenols and alkylphenol ethoxylates, phthalates, flame retardants and synthetic musk compounds. The results clearly indicated the presence of these compounds in precipitation. The concentrations ranged from the low ng l(-1) range for flame retardants to several thousands of ng l(-1) for the phthalates. Bisphenol-A was found in 30% of the samples in concentrations up to 130 ng l(-1), while alkylphenols and alkylphenol ethoxylates were found in virtually all locations in concentrations up to 920 ng l(-1) for the individual compounds. Phthalates were by far the most abundant xeno-estrogens in the precipitation samples and were found in every sample. Di-isodecyl phthalate was found in a surprisingly high concentration of almost 100 000 ng l(-1). Polybrominated flame retardants were found in the low ng l(-1) range and generally in less than 20% of the samples. Noticeable was the finding of hexabromocyclododecane, a replacement for the polybrominted diphenyl ethers at one location in a concentration of almost 2000 ng l(-1). Finally, as expected, synthetic musk compounds were detected in almost all samples. This is especially true for the polycyclic musks HHCB and AHTN. Nitro musks were found, but only on a few locations. Kriging techniques were used to calculate precipitation concentrations in between actual sampling locations to produce contour plots for a number of compounds. These plots clearly show located emission sources for a number of compounds such as bisphenol-A, nonylphenol ethoxylate, phthalates and AHTN. On the contrary, the results for HHCB and some phthalates indicated diffuse emission patterns, probably as the result of the use of consumer products containing these compounds.",
"title": "Xeno-estrogenic compounds in precipitation."
},
{
"docid": "MED-2655",
"text": "Background Broad dietary patterns have been linked to asthma but the relative contribution of specific nutrients is unclear. Soy genistein has important anti-inflammatory and other biological effects that might be beneficial in asthma. A positive association was previously reported between soy genistein intake and lung function but not with asthma exacerbations. Aims To conduct a post-hoc analysis of patients with inadequately controlled asthma enrolled in a prospective multicentre clinical trial to replicate this association. Methods A total of 300 study participants were included in the analysis. Dietary soy genistein intake was measured using the Block Soy Foods Screener. The level of soy genistein intake (little or no intake, moderate intake, or high intake) was compared with baseline lung function (pre-bronchodilator forced expiratory volume in 1 second (FEV1)) and asthma control (proportion of participants with an episode of poor asthma control (EPAC) and annualised rates of EPACs over a 6-month follow-up period. Results Participants with little or no genistein intake had a lower baseline FEV1 than those with a moderate or high intake (2.26L vs. 2.53L and 2.47L, respectively; p=0.01). EPACs were more common among those with no genistein intake than in those with a moderate or high intake (54% vs. 35% vs. 40%, respectively; p<0.001). These findings remained significant after adjustment for patient demographics and body mass index. Conclusions In patients with asthma, consumption of a diet with moderate to high amounts of soy genistein is associated with better lung function and better asthma control.",
"title": "Association of dietary soy genistein intake with lung function and asthma control: a post-hoc analysis of patients enrolled in a prospective multicentre clinical trial"
},
{
"docid": "MED-5072",
"text": "Antioxidant-rich diets are associated with reduced asthma prevalence. However, direct evidence that altering intake of antioxidant-rich foods affects asthma is lacking. The objective was to investigate changes in asthma and airway inflammation resulting from a low antioxidant diet and subsequent use of lycopene-rich treatments. Asthmatic adults (n=32) consumed a low antioxidant diet for 10 days, then commenced a randomized, cross-over trial involving 3 x 7 day treatment arms (placebo, tomato extract (45 mg lycopene/day) and tomato juice (45 mg lycopene/day)). With consumption of a low antioxidant diet, plasma carotenoid concentrations decreased, Asthma Control Score worsened, %FEV(1) and %FVC decreased and %sputum neutrophils increased. Treatment with both tomato juice and extract reduced airway neutrophil influx. Treatment with tomato extract also reduced sputum neutrophil elastase activity. In conclusion, dietary antioxidant consumption modifies clinical asthma outcomes. Changing dietary antioxidant intake may be contributing to rising asthma prevalence. Lycopene-rich supplements should be further investigated as a therapeutic intervention.",
"title": "Lycopene-rich treatments modify noneosinophilic airway inflammation in asthma: proof of concept."
},
{
"docid": "MED-1595",
"text": "Hormones work in harmony in the body, and this status must be maintained to avoid metabolic disequilibrium and the subsequent illness. Besides, it has been reported that exogenous steroids (presence in the environment and food products) influence the development of several important illnesses in humans. Endogenous steroid hormones in food of animal origin are unavoidable as they occur naturally in these products. The presence of hormones in food has been connected with several human health problems. Bovine milk contains considerable quantities of hormones and it is of particular concern. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, based on hydroxylamine derivatisation, has been developed and validated for the quantification of six sex hormones in milk [pregnenolone (P₅), progesterone (P₄), estrone (E₁), testosterone (T), androstenedione (A) and dehydroepiandrosterone (DHEA)]. This method has been applied to real raw milk samples and the existence of differences between milk from pregnant and non-pregnant cows has been statistically confirmed. Basing on a revision of existing published data, it could be concluded that maximum daily intakes for hormones are not reached through milk ingestion. Although dairy products are an important source of hormones, other products of animal origin must be considered as well for intake calculations.",
"title": "Development of an LC-MS/MS method to quantify sex hormones in bovine milk and influence of pregnancy in their levels."
},
{
"docid": "MED-4177",
"text": "Fifty-six seasonal snowpack samples were collected at remote alpine, sub-arctic, and arctic sites in eight Western US national parks during three consecutive years (2003–2005). Four current-use pesticides (CUPs) (dacthal (DCPA), chlorpyrifos, endosulfan, and γ-hexachlorocyclohexane (HCH)) and four historic-use pesticides (HUPs) (dieldrin, α-HCH, chlordane, and hexachlorobenzene (HCB)) were commonly measured at all sites, during all years. The mean coefficient of variation for pesticide concentrations was 15% for site replicate samples, 41% for intra-park replicate samples, and 59% for inter-annual replicate samples. The relative pesticide concentration profiles were consistent from year to year but unique for individual parks, indicating a regional source effect. HUP concentrations were well-correlated with regional cropland intensity when the effect of temperature on snow-air partitioning was considered. The mass of individual CUPs used in regions located one-day upwind of the parks was calculated using air mass back trajectories and this was used to explain the distribution of CUPs among the parks. The percent of the snowpack pesticide concentration due to regional transport was high (>75%) for the majority of pesticides in all parks. These results suggest that the majority of pesticide contamination in US national parks is due to pesticide use in North America.",
"title": "Variability in Pesticide Deposition and Source Contributions to Snowpack in Western US National Parks"
},
{
"docid": "MED-1749",
"text": "Pesticides associated to genetically modified foods (PAGMF), are engineered to tolerate herbicides such as glyphosate (GLYP) and gluphosinate (GLUF) or insecticides such as the bacterial toxin bacillus thuringiensis (Bt). The aim of this study was to evaluate the correlation between maternal and fetal exposure, and to determine exposure levels of GLYP and its metabolite aminomethyl phosphoric acid (AMPA), GLUF and its metabolite 3-methylphosphinicopropionic acid (3-MPPA) and Cry1Ab protein (a Bt toxin) in Eastern Townships of Quebec, Canada. Blood of thirty pregnant women (PW) and thirty-nine nonpregnant women (NPW) were studied. Serum GLYP and GLUF were detected in NPW and not detected in PW. Serum 3-MPPA and CryAb1 toxin were detected in PW, their fetuses and NPW. This is the first study to reveal the presence of circulating PAGMF in women with and without pregnancy, paving the way for a new field in reproductive toxicology including nutrition and utero-placental toxicities. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "Maternal and fetal exposure to pesticides associated to genetically modified foods in Eastern Townships of Quebec, Canada."
},
{
"docid": "MED-3889",
"text": "Contamination of retail chicken meat by Extended Spectrum Beta-Lactamase (ESBL) producing bacteria likely contributes to the increasing incidence of infections with these bacteria in humans. This study aimed to compare the prevalence and load of ESBL positive isolates between organic and conventional retail chicken meat samples, and to compare the distribution of ESBL genes, strain genotypes and co-resistance. In 2010, 98 raw chicken breasts (n=60 conventional; n=38 organic) were collected from 12 local stores in the Netherlands. Prevalence of ESBL producing micro-organisms was 100% on conventional and 84% on organic samples (p<0.001). Median loads of ESBL producing micro-organisms were 80 (range <20-1360) in conventional, and <20 (range 0-260) CFU/25 g in organic samples (p=0.001). The distribution of ESBL genes in conventional samples and organic samples was 42% versus 56%, respectively (N.S.), for CTX-M-1, 20% versus 42% (N.S.) for TEM-52, and 23% versus 3% (p<0.001) for SHV-12. CTX-M-2 (7%), SHV-2 (5%) and TEM-20 (3%) were exclusively found in conventional samples. Co-resistance rates of ESBL positive isolates were not different between conventional and organic samples (co-trimoxazole 56%, ciprofloxacin 14%, and tobramycin 2%), except for tetracycline, 73% and 46%, respectively, p<0.001). Six of 14 conventional meat samples harbored 4 MLST types also reported in humans and 5 of 10 organic samples harbored 3 MLST types also reported in humans (2 ST10, 2 ST23, ST354). In conclusion, the majority of organic chicken meat samples were also contaminated with ESBL producing E. coli, and the ESBL genes and strain types were largely the same as in conventional meat samples. Copyright © 2011 Elsevier B.V. All rights reserved.",
"title": "Comparison of ESBL contamination in organic and conventional retail chicken meat."
},
{
"docid": "MED-1747",
"text": "Knowledge of the US Public Health Syphilis Study at Tuskegee is sometime cited as a principal reason for the relatively low participation rates seen among racial/ethnic minorities, particularly African Americans, in biomedical research. However, only a few studies have actually explored this possibility. We use data from a random digit dial telephone survey of 510 African-Americans and 253 Latinos, age 18 to 45 years, to investigate associations between knowledge of the USPHS Syphilis Study at Tuskegee and endorsement of HIV/AIDS conspiracy theories. All respondents were drawn from an area of low-income, predominantly race-segregated inner city households in Los Angeles. Results indicate that African Americans were significantly more likely than Latinos to endorse HIV/AIDS conspiracy theories. Further, African Americans were more aware of the USPHS Syphilis Study at Tuskegee (SST). Nevertheless, 72% of African Americans and 94% of Latinos reported that they have never heard of the Syphilis Study at Tuskegee. Further, while awareness of the Syphilis Study at Tuskegee was a significant predictor of endorsing HIV/AIDS conspiracy theories, results suggest that other factors may be more important in accounting for low biomedical and behavioral study participation rates.",
"title": "Is there a legacy of the U.S. Public Health Syphilis Study at Tuskegee in HIV/AIDS-related beliefs among heterosexual African-Americans and Latinos?"
},
{
"docid": "MED-1151",
"text": "Background: Organically produced foods are less likely than conventionally produced foods to contain pesticide residues. Methods: We examined the hypothesis that eating organic food may reduce the risk of soft tissue sarcoma, breast cancer, non-Hodgkin lymphoma and other common cancers in a large prospective study of 623 080 middle-aged UK women. Women reported their consumption of organic food and were followed for cancer incidence over the next 9.3 years. Cox regression models were used to estimate adjusted relative risks for cancer incidence by the reported frequency of consumption of organic foods. Results: At baseline, 30%, 63% and 7% of women reported never, sometimes, or usually/always eating organic food, respectively. Consumption of organic food was not associated with a reduction in the incidence of all cancer (n=53 769 cases in total) (RR for usually/always vs never=1.03, 95% confidence interval (CI): 0.99–1.07), soft tissue sarcoma (RR=1.37, 95% CI: 0.82–2.27), or breast cancer (RR=1.09, 95% CI: 1.02–1.15), but was associated for non-Hodgkin lymphoma (RR=0.79, 95% CI: 0.65–0.96). Conclusions: In this large prospective study there was little or no decrease in the incidence of cancer associated with consumption of organic food, except possibly for non-Hodgkin lymphoma.",
"title": "Organic food consumption and the incidence of cancer in a large prospective study of women in the United Kingdom"
},
{
"docid": "MED-2657",
"text": "BACKGROUND: Japanese cedar pollinosis, caused by the pollen of the Japanese cedar tree (Cryptomeria japonica), is the commonest seasonal allergic disease in Japan. A number of epidemiological surveys have been reported on Japanese cedar pollinosis, but it has never been assessed systematically or quantitatively. To confirm the increasing prevalence of Japanese cedar pollinosis and related factors, we conducted a meta-regression analysis on population-based surveys in Japan. METHODS: We searched for data from population-based surveys in which serological methods were used to test all participants. Weighted regression of logit-transformed prevalence and sensitization rates were used to evaluate the effects of the year of survey, age, and degree of urbanization. We also analyzed the relationship between prevalence and sensitization rate. RESULTS: Thirty-eight reports with 27 subgroups for prevalence and 134 subgroups for sensitization rate were selected from the literature published in the years between 1986 and 2000. The Japanese cedar pollen sensitization rate was found to be significantly correlated with the year of survey, age, and degree of urbanization (adjusted R(2) = 0.55). The coefficient for the correlation between the prevalence and the sensitization rate revealed a statistically significant correlation (Pearson's r = 0.70, p < 0.001). CONCLUSIONS: The prevalence of Japanese cedar pollinosis among adolescents was predicted to be 28.7% in metropolitan areas and 24.5% in the general population in urban areas in the year 2004, derived from the estimated sensitization rate and the relationship between sensitization rate and prevalence. The prevalence of Japanese cedar pollinosis increased 2.6-fold between 1980 and 2000, and the prevalence differed considerably according to age and degree of urbanization. Copyright (c) 2005 S. Karger AG, Basel",
"title": "Increasing prevalence of Japanese cedar pollinosis: a meta-regression analysis."
},
{
"docid": "MED-2771",
"text": "We have previously found a positive association between milk consumption and prostate cancer risk using meta-analysis to analyze published case-control studies. In the present study, further meta-analysis was conducted to estimate the summary relative risk (RR) between the consumption of milk and dairy products and prostate cancer from cohort studies published between 1966- 2006. We found 18 relevant articles and 13 independent studies were available for our analysis. The summary RR was 1.13 (95% confidence interval = 1.02-1.24) when comparing the highest with the lowest quantile of consumption. The summary RRs by study stratification showed a positive association. A dose-response relationship was identified when combining the studies that partitioned the consumption by quintiles. We also evaluated the effects of some limitations, such as dairy classification, prostate cancer stages and publication bias, in the present study. These findings, together with the previous study, suggest that the consumption of milk and dairy products increases the risk of prostate cancer. This is biologically plausible since milk contains considerable amounts of fat, hormones, and calcium that are associated with prostate cancer risk.",
"title": "Milk consumption is a risk factor for prostate cancer in Western countries: evidence from cohort studies."
},
{
"docid": "MED-1177",
"text": "OBJECTIVE: To conduct a systematic review of published studies on the association between residential/household/domestic exposure to pesticides and childhood leukaemia, and to provide a quantitative estimate of the risk. METHODS: Publications in English were searched in MEDLINE (1966-31 December 2009) and from the reference list of identified publications. Extraction of relative risk (RR) estimates was performed independently by 2 authors using predefined inclusion criteria. Meta-rate ratio estimates (mRR) were calculated according to fixed and random-effect models. Separate analyses were conducted after stratification for exposure time windows, residential exposure location, biocide category and type of leukaemia. RESULTS: RR estimates were extracted from 13 case-control studies published between 1987 and 2009. Statistically significant associations with childhood leukaemia were observed when combining all studies (mRR: 1.74, 95% CI: 1.37-2.21). Exposure during and after pregnancy was positively associated with childhood leukaemia, with the strongest risk for exposure during pregnancy (mRR: 2.19, 95% CI: 1.92-2.50). Other stratifications showed the greatest risk estimates for indoor exposure (mRR: 1.74, 95% CI: 1.45-2.09), for exposure to insecticides (mRR: 1.73, 95% CI: 1.33-2.26) as well as for acute non-lymphocytic leukaemia (ANLL) (mRR: 2.30, 95% CI: 1.53-3.45). Outdoor exposure and exposure of children to herbicides (after pregnancy) were not significantly associated with childhood leukaemia (mRR: 1.21, 95% CI: 0.97-1.52; mRR: 1.16, 95% CI: 0.76-1.76, respectively). CONCLUSIONS: Our findings support the assumption that residential pesticide exposure may be a contributing risk factor for childhood leukaemia but available data were too scarce for causality ascertainment. It may be opportune to consider preventive actions, including educational measures, to decrease the use of pesticides for residential purposes and particularly the use of indoor insecticides during pregnancy. Copyright © 2010 Elsevier Ltd. All rights reserved.",
"title": "Residential exposure to pesticides and childhood leukaemia: a systematic review and meta-analysis."
},
{
"docid": "MED-2894",
"text": "AIM: To examine the influence of the black currant anthocyanins (BCACs) on the disease progression of open-angle glaucoma (OAG), a randomized, placebo-controlled, double-masked trial was made in 38 patients with OAG treated by antiglaucoma drops. METHODS: BCACs (50 mg/day, n = 19) or their placebos (n = 19) were orally administered once daily for a 24-month period. Systemic blood pressure, pulse rates, intraocular pressure (IOP), ocular blood circulation by laser-speckle flowgraphy, and Humphrey visual field mean deviation (MD) were measured during the 24-month period. RESULTS: As a main outcome measurement, we evaluated the difference between the groups in MD deterioration in the eye with a better MD from the trial's baseline through 24 months. A statistically significant difference was observed between the treatment groups in mean change from baseline in MD 24 months after therapy (p = 0.039, unpaired t test). Upon administration of BCACs, the ocular blood flows during the 24-month observational period increased in comparison with placebo-treated patients. However, no significant changes were observed in systemic and ocular conditions including IOP during the 24-month period. CONCLUSIONS: Our results suggest that oral administration of BCACs may be a safe and promising supplement for patients with OAG in addition to antiglaucoma medication. Copyright © 2012 S. Karger AG, Basel.",
"title": "Two-year randomized, placebo-controlled study of black currant anthocyanins on visual field in glaucoma."
},
{
"docid": "MED-2479",
"text": "BACKGROUND: The prevalence of allergic diseases seems to have increased particularly over the past 35-40 years. Furthermore, allergic disease is less common among children in the formerly socialist countries of central and Eastern Europe as compared with Western Europe. It has been suggested that a reduced microbial stimulation during infancy and early childhood would result in a slower postnatal maturation of the immune system and development of an optimal balance between TH1- and TH2-like immunity. AIMS: To test the hypothesis that allergic disease among children may be associated with differences in their intestinal microflora in two countries with a low (Estonia) and a high (Sweden) prevalence of allergy. METHODS: From a prospective study of the development of allergy in relation to environmental factors, 29 Estonian and 33 Swedish 2-year-old children were selected. They were either nonallergic (n = 36) or had a confirmed diagnosis of allergy (n = 27) as verified by typical history and at least one positive skin prick test to egg or cow's milk. Weighed samples of faeces were serially diluted (10-2-10-9) and grown under anaerobic conditions. The counts of the various genera and species were calculated for each child. In addition, the relative amounts of the particular microbes were expressed as a proportion of the total count. RESULTS: The allergic children in Estonia and Sweden were less often colonized with lactobacilli (P < 0.01), as compared with the nonallergic children in the two countries. In contrast, the allergic children harboured higher counts of aerobic micro-organisms (P < 0. 05), particularly coliforms (P < 0.01) and Staphylococcus aureus (P < 0.05). The proportions of aerobic bacteria of the intestinal flora were also higher in the allergic children (P < 0.05), while the opposite was true for anaerobes (P < 0.05). Similarly, in the allergic children the proportions of coliforms were higher (P < 0. 05) and bacteroides lower (P < 0.05) than in the nonallergic children. CONCLUSIONS: Differences in the indigenous intestinal flora might affect the development and priming of the immune system in early childhood, similar to what has been shown in rodents. The role of intestinal microflora in relation to the development of infant immunity and the possible consequences for allergic diseases later in life requires further study, particularly as it would be readily available for intervention as a means for primary prevention of allergy by the administration of probiotic bacteria.",
"title": "The intestinal microflora in allergic Estonian and Swedish 2-year-old children."
},
{
"docid": "MED-1584",
"text": "Advances in assisted reproductive technology and increases in the proportion of maternities in older women have both contributed to the steep increase in the incidence of twin pregnancies since the 1980s. Maternal and perinatal complications are higher in twins than in singleton pregnancies. A significant proportion of perinatal mortality and morbidity among twins is due to the high incidence of preterm delivery and the added complication of twin-to-twin transfusion syndrome (TTTS) in monochorionic twins. Monochorionic twins also have a much higher rate of perinatal mortality than dichorionic twins, the greatest risk being before fetal viability (<24 weeks gestation). Early diagnosis of twins and their chorionicity, close fetal surveillance, particularly of monochorionic twins, and prompt therapeutic intervention in TTS are necessary to reduce perinatal mortality. Intrapartum management in the hospital setting with anaesthetic and neonatal facilities, as well as critical assessment of mode of delivery, have led to better outcomes. Ultrasonography is a valuable tool in the management of twin pregnancy. This chapter briefly summarises these topics, with a particular focus on recent literature.",
"title": "Obstetric complications of twin pregnancies."
},
{
"docid": "MED-1753",
"text": "Given the history of GMO conflict and debate, the GM animal future is dependent on the response of the regulatory landscape and its associated range of interest groups at national, regional and international levels. Focusing on the EU and the USA, this article examines the likely form of that multi-level response, the increased role of cultural values, the contribution of new and existing interest groups and the consequent implications for the commercialization of both green and red GM animal biotechnology. Copyright © 2012. Published by Elsevier Inc.",
"title": "The current state of GMO governance: are we ready for GM animals?"
},
{
"docid": "MED-1585",
"text": "As the incidence of twin gestation increases, it is important to consider the maternal risks associated with carrying multiples. Compared with singleton gestation, there are increased risks to the mother during the antepartum, intrapartum, and postpartum periods. Certain pregnancy complications are more likely to occur during a twin gestation, including preeclampsia and other hypertensive disorders, antepartum hospitalization for preterm labor or abnormal bleeding, nutritional deficiencies, cesarean delivery, and postpartum hemorrhage. Women carrying twins may benefit from early education regarding these issues, close maternal monitoring as well as physical therapy sessions, and nutrition counseling during their pregnancies. Copyright © 2012 Elsevier Inc. All rights reserved.",
"title": "Effects of twin gestation on maternal morbidity."
},
{
"docid": "MED-1763",
"text": "The current trends of increasing incidences of testis, breast and prostate cancers are poorly understood, although it is assumed that sex hormones play a role. Disrupted sex hormone action is also believed to be involved in the increased occurrence of genital abnormalities among newborn boys and precocious puberty in girls. In this article, recent literature on sex steroid levels and their physiological roles during childhood is reviewed. It is concluded that (i) circulating levels of estradiol in prepubertal children are lower than originally claimed; (ii) children are extremely sensitive to estradiol and may respond with increased growth and/or breast development even at serum levels below the current detection limits; (iii) no threshold has been established, below which no hormonal effects can be seen in children exposed to exogenous steroids or endocrine disruptors; (iv) changes in hormone levels during fetal and prepubertal development may have severe effects in adult life and (v) the daily production rates of sex steroids in children estimated by the Food and Drug Administration in 1999 and still used in risk assessments are highly overestimated and should be revised. Because no lower threshold for estrogenic action has been established, caution should be taken to avoid unnecessary exposure of fetuses and children to exogenous sex steroids and endocrine disruptors, even at very low levels.",
"title": "The sensitivity of the child to sex steroids: possible impact of exogenous estrogens."
},
{
"docid": "MED-1169",
"text": "BACKGROUND: Conventional food production commonly uses organophosphate (OP) pesticides, which can have negative health effects, while organic food is deemed healthier because it is produced without these pesticides. Studies suggest that organic food consumption may significantly reduce OP pesticide exposure in children who have relatively higher pesticide exposure than adults due to their different diets, body weight, behaviour and less efficient metabolism. OBJECTIVES: A prospective, randomised, crossover study was conducted to determine if an organic food diet reduces organophosphate exposure in adults. METHODS: Thirteen participants were randomly allocated to consume a diet of at least 80% organic or conventional food for 7 days and then crossed over to the alternate diet. Urinary levels of six dialkylphosphate metabolites were analysed in first-morning voids collected on day 8 of each phase using GC-MS/MS with detection limits of 0.11-0.51 μg/L. RESULTS: The mean total DAP results in the organic phase were 89% lower than in the conventional phase (M=0.032 [SD=0.038] and 0.294 [SD=0.435] respectively, p=0.013). For total dimethyl DAPs there was a 96% reduction (M=0.011 [SD=0.023] and 0.252 [SD=0.403] respectively, p=0.005). Mean total diethyl DAP levels in the organic phase were half those of the conventional phase (M=0.021 [SD=0.020] and 0.042 [SD=0.038] respectively), yet the wide variability and small sample size meant the difference was not statistically significant. CONCLUSIONS: The consumption of an organic diet for one week significantly reduced OP pesticide exposure in adults. Larger scale studies in different populations are required to confirm these findings and investigate their clinical relevance. Copyright © 2014 Elsevier Inc. All rights reserved.",
"title": "Reduction in urinary organophosphate pesticide metabolites in adults after a week-long organic diet."
},
{
"docid": "MED-2888",
"text": "Age-related macular degeneration (AMD) is a common disorder that causes irreversible loss of central vision. Increased intake of foods containing zeaxanthin may be effective in preventing AMD because the macula accumulates zeaxanthin and lutein, oxygenated carotenoids with antioxidant and blue light-absorbing properties. Lycium barbarum L. is a small red berry known as Fructus lycii and wolfberry in the West, and Kei Tze and Gou Qi Zi in Asia. Wolfberry is rich in zeaxanthin dipalmitate, and is valued in Chinese culture for being good for vision. The aim of this study, which was a single-blinded, placebo-controlled, human intervention trial of parallel design, was to provide data on how fasting plasma zeaxanthin concentration changes as a result of dietary supplementation with whole wolfberries. Fasting blood was collected from healthy, consenting subjects; fourteen subjects took 15 g/d wolfberry (estimated to contain almost 3 mg zeaxanthin) for 28 d. Repeat fasting blood was collected on day 29. Age- and sex-matched controls (n 13) took no wolfberry. Responses in the two groups were compared using the Mann-Whitney test. After supplementation, plasma zeaxanthin increased 2.5-fold: mean values on day 1 and 29 were 0.038 (sem 0.003) and 0.096 (sem 0.009) micromol/l (P<0.01), respectively, for the supplementation group; and 0.038 (sem 0.003) and 0.043 (sem 0.003) micromol/l (P>0.05), respectively, for the control group. This human supplementation trial shows that zeaxanthin in whole wolfberries is bioavailable and that intake of a modest daily amount markedly increases fasting plasma zeaxanthin levels. These new data will support further study of dietary strategies to maintain macular pigment density.",
"title": "Fasting plasma zeaxanthin response to Fructus barbarum L. (wolfberry; Kei Tze) in a food-based human supplementation trial."
},
{
"docid": "MED-2464",
"text": "BACKGROUND: In recent decades, children's diet quality has changed and asthma prevalence has increased, although it remains unclear if these events are associated. OBJECTIVE: To examine children's total and component diet quality and asthma and airway hyperresponsiveness (AHR), a proxy for asthma severity. METHODS: Food frequency questionnaires adapted from the Nurses' Health Study and supplemented with foods whose nutrients which have garnered interest of late in relation to asthma were administered. From these data, diet quality scores (total and component), based on the Youth Healthy Eating Index (YHEI adapted) were developed. Asthma assessments were performed by pediatric allergists and classified by atopic status: Allergic asthma (≥1 positive skin prick test to common allergens >3 mm compared to negative control) versus non-allergic asthma (negative skin prick test). AHR was assessed via the Cockcroft technique. Participants included 270 boys (30% with asthma) and 206 girls (33% with asthma) involved in the 1995 Manitoba Prospective Cohort Study nested case-control study. Logistic regression was used to examine associations between diet quality and asthma, and multinomial logistic regression was used to examine associations between diet quality and AHR. RESULTS: Four hundred seventy six children (56.7% boys) were seen at 12.6 ± 0.5 years. Asthma and AHR prevalence were 26.2 and 53.8%, respectively. In fully adjusted models, high vegetable intake was protective against allergic asthma (OR 0.49; 95% CI 0.29-0.84; P < 0.009) and moderate/severe AHR (OR 0.58; 0.37-0.91; P < 0.019). CONCLUSIONS: Vegetable intake is inversely associated with allergic asthma and moderate/severe AHR. Copyright © 2012 Wiley Periodicals, Inc.",
"title": "Low vegetable intake is associated with allergic asthma and moderate-to-severe airway hyperresponsiveness."
},
{
"docid": "MED-1725",
"text": "Methods: During the 1980s, the National Cancer Institute conducted three case-control studies of NHL in the midwestern United States. These pooled data were used to examine pesticide exposures in farming as risk factors for NHL in men. The large sample size (n = 3417) allowed analysis of 47 pesticides simultaneously, controlling for potential confounding by other pesticides in the model, and adjusting the estimates based on a prespecified variance to make them more stable. Results: Reported use of several individual pesticides was associated with increased NHL incidence, including organophosphate insecticides coumaphos, diazinon, and fonofos, insecticides chlordane, dieldrin, and copper acetoarsenite, and herbicides atrazine, glyphosate, and sodium chlorate. A subanalysis of these \"potentially carcinogenic\" pesticides suggested a positive trend of risk with exposure to increasing numbers. Conclusion: Consideration of multiple exposures is important in accurately estimating specific effects and in evaluating realistic exposure scenarios.",
"title": "Integrative assessment of multiple pesticides as risk factors for non-Hodgkin's lymphoma among men"
},
{
"docid": "MED-1731",
"text": "Glyphosate surfactant herbicide (GlySH) toxicity is an uncommon poisoning. We report two fatalities involving suicidal ingestion of this herbicide. Both deaths occurred despite early recognition of the serious nature of the poisoning and aggressive treatment. The deaths in this series are analysed in the context of a review of existing literature. Although traditionally regarded as minimally toxic, many deaths have been reported following suicidal ingestion. Severe GlySH toxicity may be refractory even to the most intensive supportive care. The triad of pulmonary oedema, metabolic acidosis and hyperkalaemia portends poor outcome. While containing a carbon phosphorus moiety, GlySH does not exhibit organophosphate toxicity. A clinical guide to assessing severity of GlySH toxicity is proposed and treatment modalities discussed.",
"title": "Glyphosate herbicide formulation: a potentially lethal ingestion."
},
{
"docid": "MED-3887",
"text": "Summary: Antimicrobials are valuable therapeutics whose efficacy is seriously compromised by the emergence and spread of antimicrobial resistance. The provision of antibiotics to food animals encompasses a wide variety of nontherapeutic purposes that include growth promotion. The concern over resistance emergence and spread to people by nontherapeutic use of antimicrobials has led to conflicted practices and opinions. Considerable evidence supported the removal of nontherapeutic antimicrobials (NTAs) in Europe, based on the “precautionary principle.” Still, concrete scientific evidence of the favorable versus unfavorable consequences of NTAs is not clear to all stakeholders. Substantial data show elevated antibiotic resistance in bacteria associated with animals fed NTAs and their food products. This resistance spreads to other animals and humans—directly by contact and indirectly via the food chain, water, air, and manured and sludge-fertilized soils. Modern genetic techniques are making advances in deciphering the ecological impact of NTAs, but modeling efforts are thwarted by deficits in key knowledge of microbial and antibiotic loads at each stage of the transmission chain. Still, the substantial and expanding volume of evidence reporting animal-to-human spread of resistant bacteria, including that arising from use of NTAs, supports eliminating NTA use in order to reduce the growing environmental load of resistance genes.",
"title": "Food Animals and Antimicrobials: Impacts on Human Health"
},
{
"docid": "MED-4752",
"text": "A potent link to dairy seems to exist for three hormone-responsive glands. Acne, breast cancer and prostate cancer have all been linked epidemiologically to dairy intake. Although mechanisms postulated here remain to be accurately defined, the likely link involves Insulin-like Growth Factor-1 as a general stimulant, synergized by the steroid hormones present in milk. The IGF-1 may be either absorbed from milk, or stimulated by its ingestion, or both. The 5alpha-reduced compound 5alpha-pregnanedione (5α-P) present in milk is a direct precursor of dihydrotestosterone and may act through that pathway in prostate cancer, but 5α-P has also recently been shown to be capable of inducing estrogen receptors in breast cancer cells, upregulating cancer cells' sensitivity to estrogen. The introduction of exogenous hormones and growth factors into tissues that have not evolved defensive feedback inhibition of their corresponding endogenous sources is postulated as a direct stimulatory threat to these organ systems, whether for hyperplasia or neoplasia.",
"title": "Acne, dairy and cancer"
},
{
"docid": "MED-4139",
"text": "Pigs are the major animal reservoir for Yersinia enterocolitica strains, which are potentially pathogenic for humans. The goals of this study were (i) to estimate the individual animal and on-farm prevalences of Y. enterocolitica in hogs based on tonsil samples collected during National Animal Health Monitoring System Swine 2002 study and (ii) to use these data with data previously published for fecal samples to determine on-farm risk factors for Y. enterocolitica. Tonsil swabs (1,218) and fecal samples (2,847) were collected on 124 farms located in the top 17 pork-producing states. Ten percent of tonsils (122 of 1,218 samples) were positive in irgasan-tiracillin-chlorate (ITC) enrichment broth by real-time PCR, but only 5.6% of samples (68 of 1,218) were positive after subculture on the more selective cefsulodin-irgasan-novobiocin (CIN) agar. For tonsils, the on-farm prevalence based on real-time PCR detection of the ail gene in ITC enrichment broth cultures was 32% (32 of 100 premises sampled); the prevalence based on subculture in CIN agar was 19.6% (20 of 102 premises). Results of bacteriological isolation and real-time PCR analysis of tonsils and feces were combined to estimate prevalence (individual animal and farm), which was subsequently correlated with 40 farm management practices. Four factors and their accompanying odds ratios (ORs) were identified in the final regression model: location in a central state (OR = 0.3), vaccination for Escherichia coli (OR = 3.0), percentage of deaths due to scours (OR = 3.5), and presence of meat or bone meal in grower-finisher diet (OR = 4.1).",
"title": "Prevalence of Yersinia enterocolitica in market weight hogs in the United States."
},
{
"docid": "MED-2770",
"text": "Although breast and ovarian cancers are rare in Japan compared with other developed countries, the death rates for both are increasing. In Japan, dramatic lifestyle changes occurred after World War II. Over the past 50 years (1947-1997), the age-standardized death rates of breast and ovarian cancers increased about 2- and 4-fold, respectively, and the respective intake of milk, meat, and eggs increased 20-, 10-, and 7-fold. The increase in the annual death rates from breast and ovarian cancers might be due to the lifestyle changes (increased consumption of animal-derived food) that occurred after 1945. Among the food, milk and dairy products should receive particular attention since they contain considerable amounts of estrogens.",
"title": "The experience of Japan as a clue to the etiology of breast and ovarian cancers: relationship between death from both malignancies and dietary prac..."
},
{
"docid": "MED-1160",
"text": "Washing is the most practical way to remove pesticide residues in fruits and vegetables. Two commonly used kitchen dishwashing liquids (detergents) in Chinese market were tested for enhanced removal of chlorpyrifos (CHP) and chlorothalonil (CHT) in cherry tomatoes by soaking the cherry tomatoes in the detergent solutions. The critical micelle concentrations of detergent A and detergent B were about 250 mg L(-1) and 444 mg L(-1), respectively. Detergent A had a higher solubilizing ability for pesticides and hence washing effectiveness than detergent B. The apparent solubility of CHP increased with increasing detergent concentration, while that of CHT remained comparatively invariant independent of detergent concentration within the tested range. The apparent solubility of CHP was also consistently higher in solutions of both detergents as compared to CHT. Due probably to its lower logKow value, CHT was more readily washed off cherry tomatoes than CHP. In terms of washing, a duration of 10-20 min was sufficient for removal of pesticides on cherry tomatoes in distilled water and detergent solutions. The effectiveness of removing pesticides increased with increasing detergent concentration from 50 mg L(-1) to 5 g L(-1), with up to 80% CHT and 42% CHP removed. Multiple washing further increased pesticide removal. Adding 10% acetic acid to lower pH or increasing washing temperature favored pesticide removal, but 10% NaCl produced the shielding effect and substantially reduced the effectiveness of detergent A for pesticide removal. Copyright © 2013 Elsevier Ltd. All rights reserved.",
"title": "Effectiveness of dishwashing liquids in removing chlorothalonil and chlorpyrifos residues from cherry tomatoes."
},
{
"docid": "MED-4134",
"text": "Yersinia enterocolitica is considered an important food-borne pathogen impacting the pork production and processing industry in the United States. Since this bacterium is a commensal of swine, the primary goal of this study was to determine the prevalence of pathogenic Y. enterocolitica in pigs in the United Sates using feces as the sample source. A total of 2,793 fecal samples were tested for its presence in swine. Fecal samples were collected from late finisher pigs from 77 production sites in the 15 eastern and midwestern pork-producing states over a period of 27 weeks (6 September 2000 to 20 March 2001). The prevalence of ail-positive Y. enterocolitica was determined in samples using both a fluorogenic 5′ nuclease PCR assay and a culture method. The mean prevalence was 13.10% (366 of 2,793 fecal samples tested) when both PCR- and culture-positive results were combined. Forty-one of 77 premises (53.25%) contained at least one fecal sample positive for the ail sequence. The PCR assay indicated a contamination rate of 12.35% (345/2,793) compared to 4.08% (114/2,793) by the culture method. Of the 345 PCR-positive samples, 252 were culture negative, while of the 114 culture-positive samples, 21 were PCR negative. Among 77 premises, the PCR assay revealed a significantly (P < 0.05) higher percentage (46.75%, n = 36 sites) of samples positive for the pathogen (ail sequence) than the culture method (22.08%, n = 17 sites). Thus, higher sensitivity, with respect to number of samples and sites identified as positive for the PCR method compared with the culture method for detecting pathogenic Y. enterocolitica, was demonstrated in this study. The results support the hypothesis that swine are a reservoir for Y. enterocolitica strains potentially pathogenic for humans.",
"title": "Prevalence of Pathogenic Yersinia enterocolitica Strains in Pigs in the United States"
},
{
"docid": "MED-3892",
"text": "Mathematical models that estimate the proportion of foodborne illnesses attributable to food commodities at specific points in the food chain may be useful to risk managers and policy makers to formulate public health goals, prioritize interventions, and document the effectiveness of mitigations aimed at reducing illness. Using human surveillance data on laboratory-confirmed Salmonella infections from the Centers for Disease Control and Prevention and Salmonella testing data from U.S. Department of Agriculture Food Safety and Inspection Service's regulatory programs, we developed a point-of-processing foodborne illness attribution model by adapting the Hald Salmonella Bayesian source attribution model. Key model outputs include estimates of the relative proportions of domestically acquired sporadic human Salmonella infections resulting from contamination of raw meat, poultry, and egg products processed in the United States from 1998 through 2003. The current model estimates the relative contribution of chicken (48%), ground beef (28%), turkey (17%), egg products (6%), intact beef (1%), and pork (<1%) across 109 Salmonella serotypes found in food commodities at point of processing. While interpretation of the attribution estimates is constrained by data inputs, the adapted model shows promise and may serve as a basis for a common approach to attribution of human salmonellosis and food safety decision-making in more than one country.",
"title": "Application of Bayesian Techniques to Model the Burden of Human Salmonellosis Attributable to U.S. Food Commodities at the Point of Processing: Adaptation of a Danish Model"
},
{
"docid": "MED-4178",
"text": "A method has been developed to identify pesticide residues and foodstuffs for inclusion in national monitoring programs with different priority levels. It combines two chronic dietary intake indicators: ATMDI based on maximum residue levels and agricultural uses, and EDI on food contamination data. The mean and 95th percentile of exposure were calculated for 490 substances using individual and national consumption data. The results show that mean ATMDI exceeds the acceptable daily intake (ADI) for 10% of the pesticides, and the mean upper-bound EDI is above the ADI for 1.8% of substances. A seven-level risk scale is presented for substances already analyzed in food in France and substances not currently sought. Of 336 substances analyzed, 70 pesticides of concern (levels 2-5) should be particularly monitored, 22 of which are priority pesticides (levels 4 and 5). Of 154 substances not sought, 36 pesticides of concern (levels 2-4) should be included in monitoring programs, including 8 priority pesticides (level 4). In order to refine exposure assessment, analytical improvements and developments are needed to lower the analytical limits for priority pesticide/commodity combinations. Developed nationally, this method could be applied at different geographic scales. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Chronic dietary risk characterization for pesticide residues: a ranking and scoring method integrating agricultural uses and food contamination data."
},
{
"docid": "MED-1153",
"text": "Context Exposure to organophosphate (OP) pesticides is common, and although these compounds have known neurotoxic properties, few studies examined risks for children in the general population. Objective To examine the association between the concentrations of urinary dialkyl phosphate (DAP) metabolites of OPs and attention deficit/hyperactivity disorder (ADHD) in children age 8 to 15 years. Participants and Methods Cross-sectional data from the National Health and Nutrition Examination Survey (2000–2004) were available for 1,139 children representative of the general U.S. population. A structured interview with a parent was used to ascertain ADHD diagnostic status, based on slightly modified criteria of the Diagnostic and Statistical Manual of Mental Disorders-IV. Results One hundred nineteen children met the diagnostic criteria for ADHD. Children with higher concentrations of urinary DAPs, especially dimethyl alkylphosphates (DMAP), were more likely to be diagnosed with ADHD. A 10-fold increase in DMAP concentration was associated with an odds ratio (OR) of 1.55 (95% confidence intervals [CI], 1.14–2.10), after adjusting for sex, age, race/ethnicity, poverty-income ratio, fasting duration, and urinary creatinine concentration. For the most commonly detected DMAP metabolite, dimethylthiophosphate, children with levels higher than the median of detectable concentrations had double the odds of ADHD (adjusted OR, 1.93 [95% CI, 1.23–3.02]) compared with those with non-detectable levels. Conclusions These findings support the hypothesis that OP exposure, at levels common in U.S. children, may contribute to ADHD prevalence. Prospective studies are needed to establish whether this association is causal.",
"title": "ATTENTION DEFICIT/HYPERACTIVITY DISORDER AND URINARY METABOLITES OF ORGANOPHOSPHATE PESTICIDES IN U.S. CHILDREN 8–15 YEARS"
},
{
"docid": "MED-1166",
"text": "Context: Organophosphate (OP) pesticides are neurotoxic at high doses. Few studies have examined whether chronic exposure at lower levels could adversely affect children’s cognitive development. Objective: We examined associations between prenatal and postnatal exposure to OP pesticides and cognitive abilities in school-age children. Methods: We conducted a birth cohort study (Center for the Health Assessment of Mothers and Children of Salinas study) among predominantly Latino farmworker families from an agricultural community in California. We assessed exposure to OP pesticides by measuring dialkyl phosphate (DAP) metabolites in urine collected during pregnancy and from children at 6 months and 1, 2, 3.5, and 5 years of age. We administered the Wechsler Intelligence Scale for Children, 4th edition, to 329 children 7 years of age. Analyses were adjusted for maternal education and intelligence, Home Observation for Measurement of the Environment score, and language of cognitive assessment. Results: Urinary DAP concentrations measured during the first and second half of pregnancy had similar relations to cognitive scores, so we used the average of concentrations measured during pregnancy in further analyses. Averaged maternal DAP concentrations were associated with poorer scores for Working Memory, Processing Speed, Verbal Comprehension, Perceptual Reasoning, and Full-Scale intelligence quotient (IQ). Children in the highest quintile of maternal DAP concentrations had an average deficit of 7.0 IQ points compared with those in the lowest quintile. However, children’s urinary DAP concentrations were not consistently associated with cognitive scores. Conclusions: Prenatal but not postnatal urinary DAP concentrations were associated with poorer intellectual development in 7-year-old children. Maternal urinary DAP concentrations in the present study were higher but nonetheless within the range of levels measured in the general U.S. population.",
"title": "Prenatal Exposure to Organophosphate Pesticides and IQ in 7-Year-Old Children"
},
{
"docid": "MED-1173",
"text": "We designed a questionnaire concerned with attitudes and behaviour towards organic foods, environmentally friendly behaviour (EFB), and perceived consequences of organic food choice in terms of human health, the environment and animal welfare. It was mailed in 1998 to a random nation-wide sample of 2000 Swedish citizens, ages 18-65 years, and 1154 (58%) responded. Self-reported purchase of organic foods was most strongly related to perceived benefit for human health. Performance of EFBs such as refraining from car driving was also a good predictor of purchase frequency. The results indicate that egoistic motives are better predictors of the purchase of organic foods than are altruistic motives.",
"title": "Choice of organic foods is related to perceived consequences for human health and to environmentally friendly behaviour."
},
{
"docid": "MED-1182",
"text": "Background Sale of organic foods is one of the fastest growing market segments within the global food industry. People often buy organic food because they believe organic farms produce more nutritious and better tasting food from healthier soils. Here we tested if there are significant differences in fruit and soil quality from 13 pairs of commercial organic and conventional strawberry agroecosystems in California. Methodology/Principal Findings At multiple sampling times for two years, we evaluated three varieties of strawberries for mineral elements, shelf life, phytochemical composition, and organoleptic properties. We also analyzed traditional soil properties and soil DNA using microarray technology. We found that the organic farms had strawberries with longer shelf life, greater dry matter, and higher antioxidant activity and concentrations of ascorbic acid and phenolic compounds, but lower concentrations of phosphorus and potassium. In one variety, sensory panels judged organic strawberries to be sweeter and have better flavor, overall acceptance, and appearance than their conventional counterparts. We also found the organically farmed soils to have more total carbon and nitrogen, greater microbial biomass and activity, and higher concentrations of micronutrients. Organically farmed soils also exhibited greater numbers of endemic genes and greater functional gene abundance and diversity for several biogeochemical processes, such as nitrogen fixation and pesticide degradation. Conclusions/Significance Our findings show that the organic strawberry farms produced higher quality fruit and that their higher quality soils may have greater microbial functional capability and resilience to stress. These findings justify additional investigations aimed at detecting and quantifying such effects and their interactions.",
"title": "Fruit and Soil Quality of Organic and Conventional Strawberry Agroecosystems"
},
{
"docid": "MED-1730",
"text": "The United States (US) Environmental Protection Agency (EPA) and other regulatory agencies around the world have registered glyphosate as a broad-spectrum herbicide for use on multiple food and non-food use crops. To examine potential health risks in humans, we searched and reviewed the literature to evaluate whether exposure to glyphosate is associated causally with non-cancer health risks in humans. We also reviewed biomonitoring studies of glyphosate to allow for a more comprehensive discussion of issues related to exposure assessment and misclassification. Cohort, case-control and cross-sectional studies on glyphosate and non-cancer outcomes evaluated a variety of endpoints, including non-cancer respiratory conditions, diabetes, myocardial infarction, reproductive and developmental outcomes, rheumatoid arthritis, thyroid disease, and Parkinson's disease. Our review found no evidence of a consistent pattern of positive associations indicating a causal relationship between any disease and exposure to glyphosate. Most reported associations were weak and not significantly different from 1.0. Because accurate exposure measurement is crucial for valid results, it is recommended that pesticide-specific exposure algorithms be developed and validated. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "Epidemiologic studies of glyphosate and non-cancer health outcomes: a review."
},
{
"docid": "MED-3687",
"text": "This study was aimed at determining the probiotic potential of a large number of autochthonous lactic acid bacteria isolated from fruit and vegetables. Survival under simulated gastric and intestinal conditions showed that 35% of the strains, mainly belonging to the species Lactobacillus plantarum maintained high cell densities. Selected strains did not affect the immune-mediation by Caco-2 cells. All strains stimulated all 27 immune-mediators by peripheral blood mononuclear cells (PBMC). A significant (P<0.05; P<0.01) increase of the major part of cytokines and growth factors was found. A few chemokines were stimulated. Immune-mediators with pro-inflammatory activity (IL-17, EOTAXIN and IFNγ) were significantly (P<0.01) stimulated by all strains, followed by IL-1b>IP-10>IL-6>MIP1α. Stimulation of IL-12, IL-2 and IL-7 was strain dependent. Only a few strains increased the synthesis of cytokines with anti-inflammatory activity. Six L. plantarum strains were further selected. Four were defined as the strongly adhesive strains (more than 40 bacteria adhering to one Caco-2 cell), and 2 as the adhesive strains (5-40 bacteria adhering to one Caco-2 cell). Five strains grew and acidified chemically defined medium with fructo-oligosaccharides (FOS) as the only carbon source. End-products of FOS fermentation were found. All strains inhibited enterohemorragic Escherichia coli K12 and Bacillus megaterium F6 isolated from human sources. The results of this study showed that some autochthonous lactic acid bacteria from raw fruit and vegetables have functional features to be considered as novel probiotic candidates. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Novel probiotic candidates for humans isolated from raw fruits and vegetables."
},
{
"docid": "MED-1751",
"text": "There are many ways to categorise conspiracy theories. In the present study, we examined individual and demographic predictors of beliefs in commercial conspiracy theories among a British sample of over 300 women and men. Results showed many people were cynical and sceptical with regard to advertising tricks, as well as the tactics of organisations like banks and alcohol, drug and tobacco companies. Beliefs sorted into four identifiable clusters, labelled sneakiness, manipulative, change-the-rules and suppression/prevention. The high alpha for the overall scale suggested general beliefs in commercial conspiracy. Regressions suggested that those people who were less religious, more left-wing, more pessimistic, less (self-defined as) wealthy, less Neurotic and less Open-to-Experience believed there was more commercial conspiracy. Overall the individual difference variables explained relatively little of the variance in these beliefs. The implications of these findings for the literature on conspiracy theories are discussed. Limitations of the study are also discussed.",
"title": "Commercial conspiracy theories: a pilot study"
},
{
"docid": "MED-4551",
"text": "Interest has increased in the possibility that maternal dietary intake during pregnancy might influence the development of allergic disorders in children. The present prospective study examined the association of maternal intake of selected foods high in fatty acids and specific types of fatty acids during pregnancy with the risk of suspected atopic eczema among Japanese infants aged 3-4 months. Subjects were 771 mother-child pairs. Information on maternal dietary intake during pregnancy was assessed with a validated self-administered diet history questionnaire. The term 'suspected atopic eczema' was used to define an outcome based on results of our questionnaire completed by mothers 3-4 months postpartum. The risk of suspected atopic eczema was 8.4% (n = 65). Higher maternal intake of meat during pregnancy was significantly associated with an increased risk of suspected atopic eczema in the offspring: the multivariate odds ratio (OR) for the highest vs. lowest quartile was 2.59 [95% confidence interval (CI): 1.15-6.17, p for trend = 0.01]. The positive association was strengthened when the definition of the outcome was confined to a definite physician's diagnosis of atopic eczema (n = 35): the multivariate OR between extreme quartiles was 3.53 (95% CI: 1.19-12.23, p for trend = 0.02). No material exposure-response relationships were observed between maternal intake of eggs, dairy products, fish, total fat, saturated fatty acids, monounsaturated fatty acids, n-3 polyunsaturated fatty acids, alpha-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, n-6 polyunsaturated fatty acids, linoleic acid, arachidonic acid and cholesterol and the ratio of n-3 to n-6 polyunsaturated fatty acid consumption and the risk of suspected atopic eczema. Higher maternal meat intake may increase the risk of infantile atopic eczema, whereas we found no evidence that maternal intake of fish and n-3 polyunsaturated fatty acids are preventive against infantile atopic eczema. (c) 2009 John Wiley & Sons A/S",
"title": "Maternal meat and fat consumption during pregnancy and suspected atopic eczema in Japanese infants aged 3-4 months: the Osaka Maternal and Child He..."
},
{
"docid": "MED-2882",
"text": "Retinal pigment epithelium (RPE) cells are vital for retinal health. However, they are susceptible to injury with ageing and exposure to excessive light, including UV (100-380 nm) and visible (380-760 nm) radiation. To evaluate the protective effect of blueberry anthocyanins on RPE cells, in vitro cell models of replicative senescent and light-induced damage were established in the present study. After purification and fractionation, blueberry anthocyanin extracts (BAE) were yielded with total anthocyanin contents of 31·0 (SD 0·5) % and were used in this study. Replicative senescence of RPE cells was induced by repeatedly passaging cells from the fourth passage to the tenth. From the fifth passage, cultured RPE cells began to enter a replicative senescence, exhibiting reduced cell proliferation along with an increase in the number of β-galactosidase-positive cells. RPE cells maintained high cell viability (P < 0·01) and a low (P < 0·01) percentage of β-galactosidase-positive cells when treated with 0·1 μg/ml BAE. In contrast, after exposure to 2500 (SD 500) lx light (420-800 nm) for 12 h, RPE cells in the positive control (light exposure, no BAE treatment) exhibited premature senescence, low (P < 0·01) cell viability and increased (P < 0·01) vascular endothelial growth factor (VEGF) release compared with negative control cells, which were not subjected to light irradiation and BAE exposure. Correspondingly, BAE is beneficial to RPE cells by protecting these cells against light-induced damage through the suppression of ageing and apoptosis as well as the down-regulation of the over-expressed VEGF to normal level. These results demonstrate that BAE is efficacious against senescence and light-induced damage of RPE cells.",
"title": "Blueberry anthocyanins: protection against ageing and light-induced damage in retinal pigment epithelial cells."
},
{
"docid": "MED-1175",
"text": "Objectives We conducted a systematic review and meta-analysis of childhood leukemia and parental occupational pesticide exposure. Data sources Searches of MEDLINE (1950–2009) and other electronic databases yielded 31 included studies. Data extraction Two authors independently abstracted data and assessed the quality of each study. Data synthesis Random effects models were used to obtain summary odds ratios (ORs) and 95% confidence intervals (CIs). There was no overall association between childhood leukemia and any paternal occupational pesticide exposure (OR = 1.09; 95% CI, 0.88–1.34); there were slightly elevated risks in subgroups of studies with low total-quality scores (OR = 1.39; 95% CI, 0.99–1.95), ill-defined exposure time windows (OR = 1.36; 95% CI, 1.00–1.85), and exposure information collected after offspring leukemia diagnosis (OR = 1.34; 95% CI, 1.05–1.70). Childhood leukemia was associated with prenatal maternal occupational pesticide exposure (OR = 2.09; 95% CI, 1.51–2.88); this association was slightly stronger for studies with high exposure-measurement-quality scores (OR = 2.45; 95% CI, 1.68–3.58), higher confounder control scores (OR = 2.38; 95% CI, 1.56–3.62), and farm-related exposures (OR = 2.44; 95% CI, 1.53–3.89). Childhood leukemia risk was also elevated for prenatal maternal occupational exposure to insecticides (OR = 2.72; 95% CI, 1.47–5.04) and herbicides (OR = 3.62; 95% CI, 1.28–10.3). Conclusions Childhood leukemia was associated with prenatal maternal occupational pesticide exposure in analyses of all studies combined and in several subgroups. Associations with paternal occupational pesticide exposure were weaker and less consistent. Research needs include improved pesticide exposure indices, continued follow-up of existing cohorts, genetic susceptibility assessment, and basic research on childhood leukemia initiation and progression.",
"title": "A Systematic Review and Meta-analysis of Childhood Leukemia and Parental Occupational Pesticide Exposure"
},
{
"docid": "MED-2662",
"text": "A human breast cancer cell line (MCF-7) was used to develop an in vitro screening assay for the detection of xenoestrogenic environmental pollutants. MCF-7 cells were cultured in DMEM containing 5% fetal bovine serum (FBS). An estrogenic response was defined as an increase in the frequency of proliferating MCF-7 cells, and was measured using a thymidine analog, bromodeoxyuridine, and flow cytometry. Di-2-ethylhexyl phthalate (DEHP) and 4-n-nonylphenol (4-n-NP) were used as model chemicals. The proliferation rate of S-phase cells after 24 h of exposure to various concentrations of 17beta-estradiol and to model compounds was compared with a positive and a negative control, containing 1 nM 17beta-estradiol and 0.1% ethanol, respectively. DEHP and 4-n-NP increased the frequency of proliferating MCF-7 cells in a dose-dependent manner. The lowest concentration that significantly increased the proliferation of MCF-7 cells was 10 microM for DEHP and 1 microM for 4-n-NP. The results showed that the assay is accurate and quick to perform. It may prove a valuable tool for screening potential estrogen-mimicking environmental pollutants.",
"title": "Effects of xenoestrogenic environmental pollutants on the proliferation of a human breast cancer cell line (MCF-7)."
},
{
"docid": "MED-1181",
"text": "Demand for organic foods is partially driven by consumers' perceptions that they are more nutritious. However, scientific opinion is divided on whether there are significant nutritional differences between organic and non-organic foods, and two recent reviews have concluded that there are no differences. In the present study, we carried out meta-analyses based on 343 peer-reviewed publications that indicate statistically significant and meaningful differences in composition between organic and non-organic crops/crop-based foods. Most importantly, the concentrations of a range of antioxidants such as polyphenolics were found to be substantially higher in organic crops/crop-based foods, with those of phenolic acids, flavanones, stilbenes, flavones, flavonols and anthocyanins being an estimated 19 (95 % CI 5, 33) %, 69 (95 % CI 13, 125) %, 28 (95 % CI 12, 44) %, 26 (95 % CI 3, 48) %, 50 (95 % CI 28, 72) % and 51 (95 % CI 17, 86) % higher, respectively. Many of these compounds have previously been linked to a reduced risk of chronic diseases, including CVD and neurodegenerative diseases and certain cancers, in dietary intervention and epidemiological studies. Additionally, the frequency of occurrence of pesticide residues was found to be four times higher in conventional crops, which also contained significantly higher concentrations of the toxic metal Cd. Significant differences were also detected for some other (e.g. minerals and vitamins) compounds. There is evidence that higher antioxidant concentrations and lower Cd concentrations are linked to specific agronomic practices (e.g. non-use of mineral N and P fertilisers, respectively) prescribed in organic farming systems. In conclusion, organic crops, on average, have higher concentrations of antioxidants, lower concentrations of Cd and a lower incidence of pesticide residues than the non-organic comparators across regions and production seasons.",
"title": "Higher antioxidant and lower cadmium concentrations and lower incidence of pesticide residues in organically grown crops: a systematic literature review and meta-analyses"
},
{
"docid": "MED-4131",
"text": "In this article we estimate the annual cost of illness and quality-adjusted life year (QALY) loss in the United States caused by 14 of the 31 major foodborne pathogens reported on by Scallan et al. (Emerg. Infect. Dis. 17:7-15, 2011), based on their incidence estimates of foodborne illness in the United States. These 14 pathogens account for 95 % of illnesses and hospitalizations and 98 % of deaths due to identifiable pathogens estimated by Scallan et al. We estimate that these 14 pathogens cause $14.0 billion (ranging from $4.4 billion to $33.0 billion) in cost of illness and a loss of 61,000 QALYs (ranging from 19,000 to 145,000 QALYs) per year. Roughly 90 % of this loss is caused by five pathogens: nontyphoidal Salmonella enterica ($3.3 billion; 17,000 QALYs), Campylobacter spp. ($1.7 billion; 13,300 QALYs), Listeria monocytogenes ($2.6 billion; 9,400 QALYs), Toxoplasma gondii ($3 billion; 11,000 QALYs), and norovirus ($2 billion; 5,000 QALYs). A companion article attributes losses estimated in this study to the consumption of specific categories of foods. To arrive at these estimates, for each pathogen we create disease outcome trees that characterize the symptoms, severities, durations, outcomes, and likelihoods of health states associated with that pathogen. We then estimate the cost of illness (medical costs, productivity loss, and valuation of premature mortality) for each pathogen. We also estimate QALY loss for each health state associated with a given pathogen, using the EuroQol 5D scale. Construction of disease outcome trees, outcome-specific cost of illness, and EuroQol 5D scoring are described in greater detail in a second companion article.",
"title": "Annual cost of illness and quality-adjusted life year losses in the United States due to 14 foodborne pathogens."
},
{
"docid": "MED-1156",
"text": "Background: Exposure to organochlorines has been examined as a potential risk factor for non-Hodgkin lymphoma (NHL), with inconsistent results that may be related to limited statistical power or to imprecise exposure measurements. Objective: Our purpose was to examine associations between organochlorine concentrations in prediagnostic adipose tissue samples and the risk of NHL. Methods: We conducted a case–cohort study using a prospective Danish cohort of 57,053 persons enrolled between 1993 and 1997. Within the cohort we identified 256 persons diagnosed with NHL in the population-based nationwide Danish Cancer Registry and randomly selected 256 subcohort persons. We measured concentrations of 8 pesticides and 10 polychlorinated biphenyl (PCB) congeners in adipose tissue collected upon enrollment. Associations between the 18 organochlorines and NHL were analyzed in Cox regression models, adjusting for body mass index. Results: Incidence rate ratios and confidence intervals (CIs) for interquartile range increases in concentrations of dichlorodiphenyltrichlorethane (DDT), cis-nonachlor, and oxychlordane were 1.35 (95% CI: 1.10, 1.66), 1.13 (95% CI: 0.94, 1.36), and 1.11 (95% CI: 0.89, 1.38), respectively, with monotonic dose–response trends for DDT and cis-nonachlor based on categorical models. The relative risk estimates were higher for men than for women. In contrast, no clear association was found between NHL and PCBs. Conclusion: We found a higher risk of NHL in association with higher adipose tissue levels of DDT, cis-nonachlor, and oxychlordane, but no association with PCBs. This is the first study of organochlorines and NHL using prediagnostic adipose tissue samples in the exposure assessment and provides new environmental health evidence that these organochlorines contribute to NHL risk.",
"title": "A Prospective Study of Organochlorines in Adipose Tissue and Risk of Non-Hodgkin Lymphoma"
},
{
"docid": "MED-4142",
"text": "Swine confinement buildings in eastern Canada are enclosed and equipped with modern production systems to manage waste. Bioaerosols of these swine confinement buildings could be contaminated by human pathogens and antimicrobial resistant bacteria which could colonize exposed workers. We therefore wanted to analyze bioaerosols of swine confinement buildings and nasal flora of Canadian hog producers to evaluate possible colonization with human pathogens and tetracycline-resistant bacteria. Culturable and non-culturable human pathogens and tet genes were investigated in the bioaerosols of 18 barns. The nasal passages of 35 hog producers were sampled and total DNA was extracted from the calcium-alginate swabs to detect, by PCR, Campylobacter, C. perfringens, Enterococcus, E. coli, Y. enterocolitica, tetA/tetC, tetG and ribosomal protection protein genes. Airborne culturable C. perfringens, Enterococcus, E. coli, and Y. enterocolitica were present in the bioaerosols of 16, 17, 11 and 6 of the 18 facilities. Aerosolized total (culturable/non culturable) Campylobacter, C. perfringens, Enterococcus, E. coli and Y. enterocolitica were detected in 10, 6, 15, 18 and 2 barns, respectively. Tet genes were found in isolates of culturable human pathogens. TetA/tetC, tetG and ribosomal protection protein genes were detected in the bioaerosols of all 18 studied buildings. Campylobacter, C. perfringens, Enterococcus, E. coli, and Y. enterocolitica were found respectively in 4, 9, 17, 14 and one nasal flora of workers. One and 10 workers were positive for tetA/tetC and tetG genes, respectively. In swine confinement buildings, hog producers are exposed to aerosolized human pathogens and tetracycline-resistant bacteria that can contaminate the nasal flora. Copyright © 2010 Elsevier GmbH. All rights reserved.",
"title": "Human pathogens and tetracycline-resistant bacteria in bioaerosols of swine confinement buildings and in nasal flora of hog producers."
},
{
"docid": "MED-2891",
"text": "BACKGROUND: Patients who report use of herbs to their physicians may not be able to accurately describe the ingredients or recommended dosage because the products for the same herb may differ. The purpose of this study was to describe variations in label information of products for each of the 10 most commonly purchased herbs. METHODS: Products for each of 10 herbs were surveyed in a convenience sample of 20 retail stores in a large metropolitan area. Herbs were those with the greatest sales dollars in 1998: echinacea, St John's wort, Ginkgo biloba, garlic, saw palmetto, ginseng, goldenseal, aloe, Siberian ginseng, and valerian. RESULTS: Each herb had a large range in label ingredients and recommended daily dose (RDD) across available products. Strengths were not directly comparable because of ingredient variability. Among 880 products, 43% were consistent with a benchmark in ingredients and RDD, 20% in ingredients only, and 37% were either not consistent or label information was insufficient. Price per RDD was a significant predictor of consistency with the benchmark, but store type was not. CONCLUSIONS: Persons self-medicating with an herb may be ingesting ingredients substantially different from that recommended by a benchmark, both in quantity and content. Higher price per label RDD was the best predictor of consistency with a benchmark. This study demonstrates that health providers and consumers need to closely examine label ingredients of presumably the same or similar herbal products.",
"title": "Variations in product choices of frequently purchased herbs: caveat emptor."
},
{
"docid": "MED-2890",
"text": "Myopia is a worldwide public health problem. However, its understanding is incomplete, and many of its preventative and therapeutic aspects remain controversial. Nearwork is a primary, environmentally based factor in the aetiology of permanent myopia (PM), with nearwork-induced transient myopia (NITM) being a possible contributory component. A relationship between PM and NITM has been suggested, but that connection has remained somewhat indirect and elusive. However, based on recent converging evidence from clinical, laboratory and modelling studies, a five-fold argument will be advanced for a possible link between PM and NITM.",
"title": "Nearwork-induced transient myopia (NITM) and permanent myopia--is there a link?"
},
{
"docid": "MED-1146",
"text": "The current paper provides an analysis of the potential number of cancer cases that might be prevented if half the U.S. population increased its fruit and vegetable consumption by one serving each per day. This number is contrasted with an upper-bound estimate of concomitant cancer cases that might be theoretically attributed to the intake of pesticide residues arising from the same additional fruit and vegetable consumption. The cancer prevention estimates were derived using a published meta-analysis of nutritional epidemiology studies. The cancer risks were estimated using U.S. Environmental Protection Agency (EPA) methods, cancer potency estimates from rodent bioassays, and pesticide residue sampling data from the U.S. Department of Agriculture (USDA). The resulting estimates are that approximately 20,000 cancer cases per year could be prevented by increasing fruit and vegetable consumption, while up to 10 cancer cases per year could be caused by the added pesticide consumption. These estimates have significant uncertainties (e.g., potential residual confounding in the fruit and vegetable epidemiologic studies and reliance on rodent bioassays for cancer risk). However, the overwhelming difference between benefit and risk estimates provides confidence that consumers should not be concerned about cancer risks from consuming conventionally-grown fruits and vegetables. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Estimation of cancer risks and benefits associated with a potential increased consumption of fruits and vegetables."
},
{
"docid": "MED-4175",
"text": "In this study, 10 perfluorochemicals (PFCs) were measured in meat, meat products, and eggs, and in indoor dust, collected in China. Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) were the most frequently detected PFCs in these samples. Mean concentrations of PFOS and PFOA in foodstuffs were in the range of 0.05-1.99 ng/g fresh wt and 0.06-12.5 ng/g fresh wt, respectively. The mean concentrations of PFOA, perfluoroheptanoic acid (PFHpA), and PFOS in indoor dust were 205, 14.0, and 4.86 ng/g, dry wt, respectively. The estimated daily intake of PFOS and PFOA from meat, meat products and eggs (EDI(meat&eggs)) ranged from 6.00 to 9.64 ng/d and from 254 to 576 ng/d, respectively, when the values below the limit of quantitation (LOQ) were assigned as 0, and from 8.80 to 15.0 ng/d and from 255 to 577 ng/d, respectively, when the values below the LOQ were set at 1/2LOQ. The EDI(meat&eggs) of PFOS and PFOA increased with increasing family income. The estimated daily intake of PFOS and PFOA through inhalation of dust (EDI(dust)) ranged from 0.23 to 0.31 ng/d and from 9.68 to 13.4 ng/d, respectively. The daily intakes of PFOS and PFOA from the consumption of meat, meat products, and eggs, and from dust ingestion, as calculated from our samples in this study, were compared with estimated daily intake of PFCs reported from the concentrations in drinking water, fish and seafood from China. Our calculations indicate that dietary sources (EDI(dietary)) account for the overwhelming proportion of (>99% for PFOS and 98% for PFOA) total daily intake (TDI) in adults. The analyzed foodstuffs (meat, meat products, and eggs) were not the major contributors to dietary exposure to PFOS, whereas, meat was the primary contributor to dietary exposure to PFOA.",
"title": "Perfluorochemicals in meat, eggs and indoor dust in China: assessment of sources and pathways of human exposure to perfluorochemicals."
},
{
"docid": "MED-1586",
"text": "Women with a multiple pregnancy face greater risks for themselves and their infants than women pregnant with one child. Pre-pregnancy care should focus on avoiding multiple pregnancy. Early prenatal care centres on determining chorionicity and screening for fetal anomalies, with later care focusing on the presentation, prediction and management of preterm birth, and intrauterine growth restriction. The optimal timing and mode of birth are the focus of current multicentre, randomised, controlled trials. However, the data from such trials on care for women with a multiple pregnancy are limited. Many areas of care require better-quality information, including when using assisted reproductive techniques, the optimal number of embryos to be transferred, care after the diagnosis of chorionicity, and the benefits of specialised multiple pregnancy clinics. Better-quality information is required to inform clinical practice for women with complications of multiple pregnancy, including monoamniotic twin pregnancy, treatment of twin-to-twin transfusion syndrome, and care following single intrauterine fetal death.",
"title": "Evidence-based care of women with a multiple pregnancy."
},
{
"docid": "MED-5069",
"text": "It is now well known to consumers around the world that certain fruits and vegetables can help prevent or treat chronic human diseases. But, what many people don't fully appreciate is that it is not a single component in these plant-derived foods, but rather complex mixtures of interacting natural chemicals, that produce such powerful health-protective effects. These natural components accumulate simultaneously together in a plant, and provide a multifaceted defensive strategy for both the plant, and the human consumer. In order to investigate the strength of natural chemical cooperation in highly-pigmented, flavonoid-rich functional foods, our lab has relied on analysis of both whole fruits, and continuous, reliable plant cell culture production systems which accumulate anthocyanins and proanthocyanidins in high concentrations. Successive rounds of relatively gentle, rapid, and large-volume fractionations are linked to bioassay of complex to simple mixtures and semi-purified compounds. By means of this strategy, additive interactions or synergies between related compounds in health maintenance can be sorted out. Interestingly, phytochemical interactions between the same classes of compounds intensify the efficacy of flavonoid-rich fruits against multiple, not necessarily discrete, human disease conditions including CVD, cancer, metabolic syndrome, and others.",
"title": "From beans to berries and beyond: teamwork between plant chemicals for protection of optimal human health."
},
{
"docid": "MED-2643",
"text": "The incidence and/or prevalence of health problems associated with endocrine-disruption have increased. Many chemicals have endocrine-disrupting properties, including bisphenol A, some organochlorines, polybrominated flame retardants, perfluorinated substances, alkylphenols, phthalates, pesticides, polycyclic aromatic hydrocarbons, alkylphenols, solvents, and some household products including some cleaning products, air fresheners, hair dyes, cosmetics, and sunscreens. Even some metals were shown to have endocrine-disrupting properties. Many observations suggesting that endocrine disruptors do contribute to cancer, diabetes, obesity, the metabolic syndrome, and infertility are listed in this paper. An overview is presented of mechanisms contributing to endocrine disruption. Endocrine disruptors can act through classical nuclear receptors, but also through estrogen-related receptors, membrane-bound estrogen-receptors, and interaction with targets in the cytosol resulting in activation of the Src/Ras/Erk pathway or modulation of nitric oxide. In addition, changes in metabolism of endogenous hormones, cross-talk between genomic and nongenomic pathways, cross talk with estrogen receptors after binding on other receptors, interference with feedback regulation and neuroendocrine cells, changes in DNA methylation or histone modifications, and genomic instability by interference with the spindle figure can play a role. Also it was found that effects of receptor activation can differ in function of the ligand.",
"title": "Endocrine-Disrupting Chemicals: Associated Disorders and Mechanisms of Action"
},
{
"docid": "MED-4140",
"text": "A survey of 788 pigs from 120 farms was conducted to determine the within-farm prevalence of pathogenic Yersinia enterocolitica and a questionnaire of management conditions was mailed to the farms afterwards. A univariate statistical analysis with carriage and shedding as outcomes was conducted with random-effects logistic regression with farm as a clustering factor. Variables with a P value <0·15 were included into the respective multivariate random-effects logistic regression model. The use of municipal water was discovered to be a protective factor against carriage and faecal shedding of the pathogen. Organic production and buying feed from a certain feed manufacturer were also protective against total carriage. Tonsillar carriage, a different feed manufacturer, fasting pigs before transport to the slaughterhouse, higher-level farm health classification, and snout contacts between pigs were risk factors for faecal shedding. We concluded that differences in management can explain different prevalences of Y. enterocolitica between farms.",
"title": "Factors related to the prevalence of pathogenic Yersinia enterocolitica on pig farms."
},
{
"docid": "MED-3884",
"text": "Microbes have evolved over 3.5 billion years and are arguably the most adaptable organisms on earth. Restricted genetically by their inability to reproduce sexually, bacteria have acquired several additional mechanisms by which to exchange genetic material horizontally. Such mechanisms have allowed bacteria to inhabit some of the most inhospitable environments on earth. It is thus hardly surprising that when faced with a barrage of inimical chemicals (antibiotics) they have responded with an equal and opposite force. This article compares and contrasts the evolution of antimicrobial resistance to beta-lactam antibiotics over the last 70 years in two bacterial species, namely Staphylococcus aureus, a highly evolved human pathogen, and Pseudomonas aeruginosa, an opportunistic nosocomial pathogen.",
"title": "The 2009 Garrod lecture: the evolution of antimicrobial resistance: a Darwinian perspective."
},
{
"docid": "MED-1142",
"text": "Chlorinated pesticides can contain impurities of dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), and their precursors, as a result of various manufacturing processes and conditions. As precursor formation of PCDD/Fs can also be mediated by ultraviolet light (UV), this study investigated whether PCDD/Fs are formed when currently used pesticides are exposed to natural sunlight. Formulations containing pentachloronitrobenzene (PCNB; n=2) and 2,4-dichlorophenoxyacetic acid (2,4-D; n=1) were exposed to sunlight in quartz tubes, and the concentration of 93 PCDD/F congeners were monitored over time. Considerable formation of PCDD/Fs was observed in both PCNB formulations (by up to 5600%, to a maximum concentration of 57000 μg ∑PCDD/F kg(-1)) as well as the 2,4-D formulation (by 3000%, to 140 μg ∑PCDD/F kg(-1)). TEQ also increased by up to 980%, to a maximum concentration of 28 μg kg(-1) in PCNB, but did not change in the 2,4-D formulation. Assuming similar yields as observed in the present study as a worst case scenario the use of PCNB in Australia may result in the formation of 155 g TEQ annum(-1), contributed primarily by OCDD formation. This warrants detailed evaluations on the contemporary release of PCDD/Fs to the environment after the use of pesticides. Changes in congener profiles (including the ratio of PCDDs to PCDFs (DF ratio)) suggest that pesticide sources of PCDD/Fs after sunlight exposure may not be recognized based on matching source fingerprints established from manufacturing impurities. These changes also provide preliminary insights into the possible formation routes and types of precursors involved. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Formation of dioxins during exposure of pesticide formulations to sunlight."
},
{
"docid": "MED-1748",
"text": "Our bloodstream is considered to be an environment well separated from the outside world and the digestive tract. According to the standard paradigm large macromolecules consumed with food cannot pass directly to the circulatory system. During digestion proteins and DNA are thought to be degraded into small constituents, amino acids and nucleic acids, respectively, and then absorbed by a complex active process and distributed to various parts of the body through the circulation system. Here, based on the analysis of over 1000 human samples from four independent studies, we report evidence that meal-derived DNA fragments which are large enough to carry complete genes can avoid degradation and through an unknown mechanism enter the human circulation system. In one of the blood samples the relative concentration of plant DNA is higher than the human DNA. The plant DNA concentration shows a surprisingly precise log-normal distribution in the plasma samples while non-plasma (cord blood) control sample was found to be free of plant DNA.",
"title": "Complete Genes May Pass from Food to Human Blood"
},
{
"docid": "MED-2895",
"text": "PURPOSE: The retinal carotenoids lutein (L) and zeaxanthin (Z) that form the macular pigment (MP) may help to prevent neovascular age-related macular degeneration. The purpose of this study was to determine whether MP density in the retina could be raised by increasing dietary intake of L and Z from foods. METHODS: Macular pigment was measured psychophysically for 13 subjects. Serum concentrations of L, Z, and beta-carotene were measured by high-performance liquid chromatography. Eleven subjects modified their usual daily diets by adding 60 g of spinach (10.8 mg L, 0.3 mg Z, 5 mg beta-carotene) and ten also added 150 g of corn (0.3 mg Z, 0.4 mg L); two other subjects were given only corn. Dietary modification lasted up to 15 weeks. RESULTS: For the subjects fed spinach or spinach and corn, three types of responses to dietary modification were identified: Eight \"retinal responders\" had increases in serum L (mean, 33%; SD, 22%) and in MP density (mean, 19%; SD, 11%); two \"retinal nonresponders\" showed substantial increases in serum L (mean, 31%) but not in MP density (mean, -11%); one \"serum and retinal nonresponder\" showed no changes in serum L, Z, or beta-carotene and no change in MP density. For the two subjects given only corn, serum L changed little (+11%, -6%), but in one subject serum Z increased (70%) and MP density increased (25%). CONCLUSIONS: Increases in MP density were obtained within 4 weeks of dietary modification for most, but not all, subjects. When MP density increased with dietary modification, it remained elevated for at least several months after resuming an unmodified diet. Augmentation of MP for both experimental and clinical investigation appears to be feasible for many persons.",
"title": "Dietary modification of human macular pigment density."
},
{
"docid": "MED-1170",
"text": "OBJECTIVE: To examine the potential association between parental occupational exposure to pesticides and the occurrence of brain tumors in children and young adults. METHODS: Studies identified from a MEDLINE search through 15 January 2013 and from the reference lists of identified publications were submitted to a systematic review and meta-analysis. Relative risk estimates were extracted from 20 studies published between 1974 and 2010. Most of the retrieved studies involved farm/agricultural jobs. Summary ratio estimates (SR) were calculated according to fixed and random-effect meta-analysis models. Separate analyses were conducted after stratification for study design, exposure parameters, disease definition, geographic location and age at diagnosis. RESULTS: Statistically significant associations were observed for parents potentially exposed to pesticides in occupational settings and the occurrence of brain tumor in their offspring after combining all case-control studies (summary odds ratio [SOR]: 1.30; 95%: 1.11, 1.53) or all cohort studies (summary rate ratio [SRR]: 1.53; 95% CI: 1.20, 1.95). Significantly increased risks were seen for prenatal exposure windows, for either exposed parent, for exposure defined as to pesticides as well as by occupational/industry title, for astroglial brain tumors and after combining case-control studies from North America or cohort studies from Europe. CONCLUSIONS: This meta-analysis supports an association between parental occupational exposure to pesticides and brain tumors in children and young adults, and adds to the evidence leading to the recommendation of minimizing (parental) occupational exposure to pesticides. These results must, however, be interpreted with caution because the impact of work-related factors others than pesticide exposure is not known. Copyright © 2013 Elsevier Ltd. All rights reserved.",
"title": "Parental occupational exposure to pesticides as risk factor for brain tumors in children and young adults: a systematic review and meta-analysis."
},
{
"docid": "MED-2649",
"text": "Background Dietary fat exerts numerous complex effects on proinflammatory and immunologic pathways. Several epidemiological studies have examined the relationships between intake of fatty acids and/or foods high in fat and allergic rhinitis, but have provided conflicting findings. The current cross-sectional study investigated such relationships in Japan. Methods Study subjects were 1745 pregnant women. The definition of rhinoconjunctivitis was based on criteria from the International Study of Asthma and Allergies in Childhood. Information on dietary factors was collected using a validated self-administered diet history questionnaire. Adjustment was made for age; gestation; region of residence; number of older siblings; number of children; smoking; secondhand smoke exposure at home and at work; family history of asthma, atopic eczema, and allergic rhinitis; household income; education; and body mass index. Results The prevalence of rhinoconjunctivitis in the past 12 months was 25.9%. Higher meat intake was significantly associated with an increased prevalence of rhinoconjunctivitis: the adjusted odds ratio between extreme quartiles was 1.71 (95% confidence interval: 1.25-2.35, P for trend = 0.002). No measurable association was found between fish intake and rhinoconjunctivitis. Intake of total fat, saturated fatty acids, monounsaturated fatty acids, n-3 polyunsaturated fatty acids, α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, n-6 polyunsaturated fatty acids, linoleic acid, arachidonic acid, and cholesterol and the ratio of n-3 to n-6 polyunsaturated fatty acid intake were not evidently related to the prevalence of rhinoconjunctivitis. Conclusions The current results suggest that meat intake may be positively associated with the prevalence of rhinoconjunctivitis in young adult Japanese women.",
"title": "Dietary meat and fat intake and prevalence of rhinoconjunctivitis in pregnant Japanese women: baseline data from the Kyushu Okinawa Maternal and Child Health Study"
},
{
"docid": "MED-2661",
"text": "This paper presents the results of an investigation on the occurrence of alkylphenols (APs) and their ethoxylates (APEs) in 8 edible marine species from the Adriatic Sea and tries to estimate the corresponding intake for the Italian population. Two crustaceans, Nephrops norvegicus (Norway lobster) and Squilla mantis (spottail mantis shrimp), plus six fish species, Engraulis enchrascicolus (anchovy), Scomber scombrus (Atlantic mackerel), Merluccius merluccius (European hake), Mullus barbatus (red mullet), Solea vulgaris (common sole) and Lophius piscatorius (angler) were analyzed for their content of nonylphenol (NP), octylphenol (OP) and octylphenol polyethoxylates (OPEs). These compounds were found in all analysed samples. NP was detected at the highest concentrations: 118-399 and 9.5-1431 ng g(-1) fresh weight (fw) respectively in crustaceans and fish. OP was found at respective levels of 2.7-4.7 and 0.3-3.8 ng g(-1) fw in crustaceans and fish, whereas OPE was determined at respective concentrations of 1.2-16.8 and 0.2-21.1 ng g(-1) fw in the same species. These results, together with those from a previous study on 4 edible mollusc, allow to estimate respective daily intakes for NP, OP, and OPE of about 12, 0.1, and 0.1 microg day(-1) for an Italian adult living along the Adriatic Coast. In relation to NP and OP, these intakes are much lower than the doses associated with toxic effects in laboratory animals (9 mg kg(-1) bw for rats). Nevertheless, data of exposure from other sources to these chemicals and others with similar biological characteristics are needed.",
"title": "Alkylphenols and alkylphenol ethoxylates contamination of crustaceans and fishes from the Adriatic Sea (Italy)."
},
{
"docid": "MED-2646",
"text": "BACKGROUND: Certain foods may increase or decrease the risk of developing asthma, rhinoconjunctivitis and eczema. We explored the impact of the intake of types of food on these diseases in Phase Three of the International Study of Asthma and Allergies in Childhood. METHODS: Written questionnaires on the symptom prevalence of asthma, rhinoconjunctivitis and eczema and types and frequency of food intake over the past 12 months were completed by 13-14-year-old adolescents and by the parents/guardians of 6-7-year-old children. Prevalence ORs were estimated using logistic regression, adjusting for confounders, and using a random (mixed) effects model. RESULTS: For adolescents and children, a potential protective effect on severe asthma was associated with consumption of fruit ≥3 times per week (OR 0.89, 95% CI 0.82 to 0.97; OR 0.86, 95% CI 0.76 to 0.97, respectively). An increased risk of severe asthma in adolescents and children was associated with the consumption of fast food ≥3 times per week (OR 1.39, 95% CI 1.30 to 1.49; OR 1.27, 95% CI 1.13 to 1.42, respectively), as well as an increased risk of severe rhinoconjunctivitis and severe eczema. Similar patterns for both ages were observed for regional analyses, and were consistent with gender and affluence categories and with current symptoms of all three conditions. CONCLUSIONS: If the association between fast foods and the symptom prevalence of asthma, rhinoconjunctivitis and eczema is causal, then the findings have major public health significance owing to the rising consumption of fast foods globally.",
"title": "Do fast foods cause asthma, rhinoconjunctivitis and eczema? Global findings from the International Study of Asthma and Allergies in Childhood (ISAA..."
},
{
"docid": "MED-1144",
"text": "Public risk perceptions and demand for safer food are important factors shaping agricultural production practices in the United States. Despite documented food safety concerns, little attempt has been made to elicit consumers' subjective risk judgments for a range of food safety hazards or to identify factors most predictive of perceived food safety risks. In this study, over 700 conventional and organic fresh produce buyers in the Boston area were surveyed for their perceived food safety risks. Survey results showed that consumers perceived relatively high risks associated with the consumption and production of conventionally grown produce compared with other public health hazards. For example, conventional and organic food buyers estimated the median annual fatality rate due to pesticide residues on conventionally grown food to be about 50 per million and 200 per million, respectively, which is similar in magnitude to the annual mortality risk from motor vehicle accidents in the United States. Over 90% of survey respondents also perceived a reduction in pesticide residue risk associated with substituting organically grown produce for conventionally grown produce, and nearly 50% perceived a risk reduction due to natural toxins and microbial pathogens. Multiple regression analyses indicate that only a few factors are consistently predictive of higher risk perceptions, including feelings of distrust toward regulatory agencies and the safety of the food supply. A variety of factors were found to be significant predictors of specific categories of food hazards, suggesting that consumers may view food safety risks as dissimilar from one another. Based on study findings, it is recommended that future agricultural policies and risk communication efforts utilize a comparative risk approach that targets a range of food safety hazards.",
"title": "Perceived risks of conventional and organic produce: pesticides, pathogens, and natural toxins."
},
{
"docid": "MED-4179",
"text": "Rainfall samples were collected during the 2003 and 2004 growing seasons at four agricultural locales across the USA in Maryland, Indiana, Nebraska, and California. The samples were analyzed for 21 insecticides, 18 herbicides, three fungicides, and 40 pesticide degradates. Data from all sites combined show that 7 of the 10 most frequently detected pesticides were herbicides, with atrazine (70%) and metolachlor (83%) detected at every site. Dacthal, acetochlor, simazine, alachlor, and pendimethalin were detected in more than 50% of the samples. Chlorpyrifos, carbaryl, and diazinon were the only insecticides among the 10 most frequently detected compounds. Of the remaining pesticide parent compounds, 18 were detected in fewer than 30% of the samples, and 13 were not detected. The most frequently detected degradates were deethylatrazine; the oxygen analogs (OAs) of the organophosphorus insecticides chlorpyrifos, diazinon, and malathion; and 1-napthol (degradate of carbaryl). Deethylatrazine was detected in nearly 70% of the samples collected in Maryland, Indiana, and Nebraska but was detected only once in California. The OAs of chlorpyrifos and diazinon were detected primarily in California. Degradates of the acetanilide herbicides were rarely detected in rain, indicating that they are not formed in the atmosphere or readily volatilized from soils. Herbicides accounted for 91 to 98% of the total pesticide mass deposited by rain except in California, where insecticides accounted for 61% in 2004. The mass of pesticides deposited by rainfall was estimated to be less than 2% of the total applied in these agricultural areas.",
"title": "Pesticides in rain in four agricultural watersheds in the United States."
},
{
"docid": "MED-1745",
"text": "The composition of glyphosate-tolerant (Roundup Ready) soybean 40-3-2 was compared with that of conventional soybean grown in Romania in 2005 as part of a comparative safety assessment program. Samples were collected from replicated field trials, and compositional analyses were performed to measure proximates (moisture, fat, ash, protein, and carbohydrates by calculation), fiber, amino acids, fatty acids, isoflavones, raffinose, stachyose, phytic acid, trypsin inhibitor, and lectin in grain as well as proximates and fiber in forage. The mean values for all biochemical components assessed for Roundup Ready soybean 40-30-2 were similar to those of the conventional control and were within the published range observed for commercial soybean. The compositional profile of Roundup Ready soybean 40-3-2 was also compared to that of conventional soybean varieties grown in Romania by calculating a 99% tolerance interval to describe compositional variability in the population of traditional soybean varieties already on the marketplace. These comparisons, together with the history of the safe use of soybean as a common component of animal feed and human food, lead to the conclusion that Roundup Ready soybean 40-3-2 is compositionally equivalent to and as safe and nutritious as conventional soybean varieties grown commercially.",
"title": "Chemical composition of glyphosate-tolerant soybean 40-3-2 grown in Europe remains equivalent with that of conventional soybean (Glycine max L.)."
},
{
"docid": "MED-4133",
"text": "BACKGROUND: Yersinia enterocolitica (YE) infection has long been implicated in the pathogenesis of Graves' disease (GD). The association between YE and GD could, however, also be due to common genetic or environmental factors affecting the development of both YE infection and GD. This potential confounding can be minimized by investigation of twin pairs discordant for GD. AIM: To examine whether YE infection is associated with GD. DESIGN: We first conducted a classical case-control study of individuals with (61) and without (122) GD, and then a case-control study of twin pairs (36) discordant for GD. METHODS: Immunoglobulin (Ig)A and IgG antibodies to virulence-associated Yersinia outer membrane proteins (YOPs) were measured. MAIN OUTCOME MEASURES: The prevalence of YOP IgA and IgG antibodies. RESULTS: Subjects with GD had a higher prevalence of YOP IgA (49%vs. 34%, P = 0.054) and YPO IgG (51%vs. 35%, P = 0.043) than the external controls. The frequency of chronic YE infection, reflected by the presence of both IgA and IgG YOP antibodies, was also higher among cases than controls (49%vs. 33%, P = 0.042). Similar results were found in twin pairs discordant for GD. In the case-control analysis, individuals with GD had an increased odds ratio (OR) of YE infection: IgA 1.84 (95% CI 0.99-3.45) and IgG 1.90 (95% CI 1.02-3.55). In the co-twin analysis, the twin with GD also had an increased OR of YE infection: IgA 5.5 (95% CI 1.21-24.81) and IgG 5.0 (95% CI 1.10-22.81). CONCLUSION: The finding of an association between GD and YE in the case-control study and within twin pairs discordant for GD supports the notion that YE infection plays an aetiological role in the occurrence of GD, or vice versa. Future studies should examine the temporal relationship of this association in more depth.",
"title": "Too early to dismiss Yersinia enterocolitica infection in the aetiology of Graves' disease: evidence from a twin case-control study."
},
{
"docid": "MED-1162",
"text": "Consumers are frequently urged to avoid imported foods as well as specific fruits and vegetables due to health concerns from pesticide residues and are often encouraged to choose organic fruits and vegetables rather than conventional forms. Studies have demonstrated that while organic fruits and vegetables have lower levels of pesticide residues than do conventional fruits and vegetables, pesticide residues are still frequently detected on organic fruits and vegetables; typical dietary consumer exposure to pesticide residues from conventional fruits and vegetables does not appear to be of health significance. Similarly, research does not demonstrate that imported fruits and vegetables pose greater risks from pesticide residues than do domestic fruits and vegetables or that specific fruits and vegetables singled out as being the most highly contaminated by pesticides should be avoided in their conventional forms.",
"title": "Pesticide residues in imported, organic, and \"suspect\" fruits and vegetables."
},
{
"docid": "MED-2492",
"text": "Background: Inorganic arsenic (iAs) causes cancer and possibly other adverse health outcomes. Arsenic-based drugs are permitted in poultry production; however, the contribution of chicken consumption to iAs intake is unknown. Objectives: We sought to characterize the arsenic species profile in chicken meat and estimate bladder and lung cancer risk associated with consuming chicken produced with arsenic-based drugs. Methods: Conventional, antibiotic-free, and organic chicken samples were collected from grocery stores in 10 U.S. metropolitan areas from December 2010 through June 2011. We tested 116 raw and 142 cooked chicken samples for total arsenic, and we determined arsenic species in 65 raw and 78 cooked samples that contained total arsenic at ≥ 10 µg/kg dry weight. Results: The geometric mean (GM) of total arsenic in cooked chicken meat samples was 3.0 µg/kg (95% CI: 2.5, 3.6). Among the 78 cooked samples that were speciated, iAs concentrations were higher in conventional samples (GM = 1.8 µg/kg; 95% CI: 1.4, 2.3) than in antibiotic-free (GM = 0.7 µg/kg; 95% CI: 0.5, 1.0) or organic (GM = 0.6 µg/kg; 95% CI: 0.5, 0.8) samples. Roxarsone was detected in 20 of 40 conventional samples, 1 of 13 antibiotic-free samples, and none of the 25 organic samples. iAs concentrations in roxarsone-positive samples (GM = 2.3 µg/kg; 95% CI: 1.7, 3.1) were significantly higher than those in roxarsone-negative samples (GM = 0.8 µg/kg; 95% CI: 0.7, 1.0). Cooking increased iAs and decreased roxarsone concentrations. We estimated that consumers of conventional chicken would ingest an additional 0.11 µg/day iAs (in an 82-g serving) compared with consumers of organic chicken. Assuming lifetime exposure and a proposed cancer slope factor of 25.7 per milligram per kilogram of body weight per day, this increase in arsenic exposure could result in 3.7 additional lifetime bladder and lung cancer cases per 100,000 exposed persons. Conclusions: Conventional chicken meat had higher iAs concentrations than did conventional antibiotic-free and organic chicken meat samples. Cessation of arsenical drug use could reduce exposure and the burden of arsenic-related disease in chicken consumers.",
"title": "Roxarsone, Inorganic Arsenic, and Other Arsenic Species in Chicken: A U.S.-Based Market Basket Sample"
},
{
"docid": "MED-1139",
"text": "There is growing evidence on the association between long-term exposure to pesticides in occupational settings and an elevated rate of chronic diseases, including different types of cancer. However, data on non-occupational exposures are scarce to draw any conclusion. The objective of this study was to investigate the putative associations of environmental pesticide exposures in the general population with several cancer sites and to discuss potential carcinogenic mechanisms by which pesticides develop cancer. A population-based case-control study was conducted among people residing in 10 Health districts from Andalusia (South Spain) to estimate the risk of cancer at different sites. Health districts were categorized into areas of high and low environmental pesticide exposure based on two quantitative criteria: number of hectares devoted to intensive agriculture and pesticide sales per capita. The study population consisted of 34,205 cancer cases and 1,832,969 age and health district matched controls. Data were collected by computerized hospital records (minimum dataset) between 1998 and 2005. Prevalence rates and the risk of cancer at most organ sites were significantly higher in districts with greater pesticide use related to those with lower pesticide use. Conditional logistic regression analyses showed that the population living in areas with high pesticide use had an increased risk of cancer at all sites studied (odds ratios between 1.15 and 3.45) with the exception of Hodgkin's disease and non-Hodgkin lymphoma. The results of this study support and extend previous evidence from occupational studies indicating that environmental exposure to pesticides may be a risk factor for different types of cancer at the level of the general population. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.",
"title": "Environmental exposure to pesticides and cancer risk in multiple human organ systems."
},
{
"docid": "MED-1178",
"text": "BACKGROUND: The health benefits of organic foods are unclear. PURPOSE: To review evidence comparing the health effects of organic and conventional foods. DATA SOURCES: MEDLINE (January 1966 to May 2011), EMBASE, CAB Direct, Agricola, TOXNET, Cochrane Library (January 1966 to May 2009), and bibliographies of retrieved articles. STUDY SELECTION: English-language reports of comparisons of organically and conventionally grown food or of populations consuming these foods. DATA EXTRACTION: 2 independent investigators extracted data on methods, health outcomes, and nutrient and contaminant levels. DATA SYNTHESIS: 17 studies in humans and 223 studies of nutrient and contaminant levels in foods met inclusion criteria. Only 3 of the human studies examined clinical outcomes, finding no significant differences between populations by food type for allergic outcomes (eczema, wheeze, atopic sensitization) or symptomatic Campylobacter infection. Two studies reported significantly lower urinary pesticide levels among children consuming organic versus conventional diets, but studies of biomarker and nutrient levels in serum, urine, breast milk, and semen in adults did not identify clinically meaningful differences. All estimates of differences in nutrient and contaminant levels in foods were highly heterogeneous except for the estimate for phosphorus; phosphorus levels were significantly higher than in conventional produce, although this difference is not clinically significant. The risk for contamination with detectable pesticide residues was lower among organic than conventional produce (risk difference, 30% [CI, -37% to -23%]), but differences in risk for exceeding maximum allowed limits were small. Escherichia coli contamination risk did not differ between organic and conventional produce. Bacterial contamination of retail chicken and pork was common but unrelated to farming method. However, the risk for isolating bacteria resistant to 3 or more antibiotics was higher in conventional than in organic chicken and pork (risk difference, 33% [CI, 21% to 45%]). LIMITATION: Studies were heterogeneous and limited in number, and publication bias may be present. CONCLUSION: The published literature lacks strong evidence that organic foods are significantly more nutritious than conventional foods. Consumption of organic foods may reduce exposure to pesticide residues and antibiotic-resistant bacteria. PRIMARY FUNDING SOURCE: None.",
"title": "Are organic foods safer or healthier than conventional alternatives?: a systematic review."
},
{
"docid": "MED-2763",
"text": "Despite compelling statistics that show we could eliminate 80%of all heart disease and strokes, 90% of all diabetes, and 60% of all cancers with basic lifestyle changes, we have failed to motivate the public to make these changes and failed to motivate policy makers to make healthy choices the easiest choice. Dr. Katz suggests we have failed because we have focused too much on statistics and too little on passion. He implores all of us to tap into people's passion by connecting each of these statistics with a human story.",
"title": "Facing the facelessness of public health: what's the public got to do with it?"
},
{
"docid": "MED-4141",
"text": "To study the origin and spread of Yersinia enterocolitica among pigs, fecal and blood samples were repeatedly taken on a fattening farm. A few piglets were found to be already infected on breeding farms. After the piglets were mixed, the infection spread through the whole unit. Eventually, all the pigs excreted the pathogen.",
"title": "Piglets Are a Source of Pathogenic Yersinia enterocolitica on Fattening-Pig Farms"
},
{
"docid": "MED-2658",
"text": "The prevalence of allergic diseases has increased in recent decades. Allergic diseases, particularly asthma, are complex diseases with strong gene-environment interactions. Epidemiological studies have identified a variety of risk factors for the development of allergic diseases. Among them, endocrine-disrupting chemicals (EDCs) play an important role in triggering or exacerbating these diseases. 4-Nonylphenol (NP) and 4-octylphenol (OP)--two major alkylphenols--have been recognized as common toxic and xenobiotic endocrine disrupters. Due to their low solubility, high hydrophobicity, and low estrogenic activity, they tend to accumulate in the human body and may be associated with the adverse effects of allergic diseases. Recently, new evidence has supported the importance of alkylphenols in the in vitro allergic response. This review focuses on the effects of alkylphenols on several key cell types in the context of allergic inflammation. Copyright © 2012. Published by Elsevier B.V.",
"title": "Alkylphenols--potential modulators of the allergic response."
},
{
"docid": "MED-4132",
"text": "Understanding the relative public health impact of major microbiological hazards across the food supply is critical for a risk-based national food safety system. This study was conducted to estimate the U.S. health burden of 14 major pathogens in 12 broad categories of food and to then rank the resulting 168 pathogen-food combinations. These pathogens examined were Campylobacter, Clostridium perfringens, Escherichia coli O157:H7, Listeria monocytogenes, norovirus, Salmonella enterica, Toxoplasma gondii, and all other FoodNet pathogens. The health burden associated with each pathogen was measured using new estimates of the cost of illness and loss of quality-adjusted life years (QALYs) from acute and chronic illness and mortality. A new method for attributing illness to foods was developed that relies on both outbreak data and expert elicitation. This method assumes that empirical data are generally preferable to expert judgment; thus, outbreak data were used for attribution except where evidence suggests that these data are considered not representative of food attribution. Based on evaluation of outbreak data, expert elicitation, and published scientific literature, outbreak-based attribution estimates for Campylobacter, Toxoplasma, Cryptosporidium, and Yersinia were determined not representative; therefore, expert-based attribution were included for these four pathogens. Sensitivity analyses were conducted to assess the effect of attribution data assumptions on rankings. Disease burden was concentrated among a relatively small number of pathogen-food combinations. The top 10 pairs were responsible for losses of over $8 billion and 36,000 QALYs, or more than 50 % of the total across all pairs. Across all 14 pathogens, poultry, pork, produce, and complex foods were responsible for nearly 60 % of the total cost of illness and loss of QALYs.",
"title": "Ranking the disease burden of 14 pathogens in food sources in the United States using attribution data from outbreak investigations and expert elic..."
},
{
"docid": "MED-1746",
"text": "The global area covered with transgenic (genetically modified) crops has rapidly increased since their introduction in the mid-1990s. Most of these crops have been rendered herbicide resistant, for which it can be envisaged that the modification has an impact on the profile and level of herbicide residues within these crops. In this article, the four main categories of herbicide resistance, including resistance to acetolactate-synthase inhibitors, bromoxynil, glufosinate and glyphosate, are reviewed. The topics considered are the molecular mechanism underlying the herbicide resistance, the nature and levels of the residues formed and their impact on the residue definition and maximum residue limits (MRLs) defined by the Codex Alimentarius Commission and national authorities. No general conclusions can be drawn concerning the nature and level of residues, which has to be done on a case-by-case basis. International residue definitions and MRLs are still lacking for some herbicide-crop combinations, and harmonisation is therefore recommended. Copyright © 2011 Society of Chemical Industry.",
"title": "The impact of altered herbicide residues in transgenic herbicide-resistant crops on standard setting for herbicide residues."
},
{
"docid": "MED-4138",
"text": "Yersinia enterocolitica is a zoonotic agent that causes gastrointestinal disease in humans, as well as reactive arthritis and erythema nodosum. Enteropathogenic Yersinia are the etiological agents for yersiniosis, which can be acquired through the consumption of contaminated foods. As porcine animals are the main carriers of Y. enterocolitica, food safety measures to minimize human infection are of increasing interest to the scientific and medical community. In this review, we examine why it is imperative that information on the reservoirs, prevalence, virulence, and ability of this pathogen to survive in different environments is further investigated to provide rational measures to prevent or decrease associated disease risks.",
"title": "Yersinia enterocolitica: a brief review of the issues relating to the zoonotic pathogen, public health challenges, and the pork production chain."
},
{
"docid": "MED-4130",
"text": "We investigated characteristics of Yersinia enterocolitica infection in Ontario finisher pig herds. Our specific objectives were to estimate or test: prevalence of Y. enterocolitica shedding in finisher pigs, bioserotype distribution, agreement between the herd-level tests based on sampling pig and pooled fecal samples, whether bioserotypes cluster by farms, and whether Y. enterocolitica-positive herds cluster spatially. In total, 3747 fecal samples were collected from 100 farms over the years 2001, 2002, and 2004 (250 total herd visits). Fecal samples were tested by culture and positive isolates were biotyped and serotyped. Apparent pig-level prevalence of Y. enterocolitica was 1.8%, 3.2%, and 12.5% in 2001, 2002, and 2004, respectively. Estimated true pig-level prevalence of Y. enterocolitica was 5.1%, 9.1%, and 35.1% in 2001, 2002, and 2004, respectively. Herd-level prevalence was 16.3%, 17.9%, and 37.5% in 2001, 2002, and 2004, respectively. In all years, the most common bioserotype was 4, O:3, followed by bioserotype 2, O:5,27. Kappa between herd-level status based on pig and pooled samples ranged between 0.51 and 0.68 for biotype 1A and bioserotype 4, O:3, respectively. For 4, O:3, a significant bias in discordant pairs was detected, indicating that pig samples were more sensitive than pooled samples in declaring a herd as positive. Farms tended to be repeatedly positive with the same bioserotype, but positive study farms did not cluster spatially (suggesting lack of between herd transmission and lack of a common geographic risk factor). Copyright 2009 Elsevier B.V. All rights reserved.",
"title": "Prevalence of Yersinia enterocolitica shedding and bioserotype distribution in Ontario finisher pig herds in 2001, 2002, and 2004."
},
{
"docid": "MED-1176",
"text": "Many studies have investigated the neurodevelopmental effects of prenatal and early childhood exposures to organophosphate (OP) pesticides among children, but they have not been collectively evaluated. The aim of the present article is to synthesize reported evidence over the last decade on OP exposure and neurodevelopmental effects in children. The Data Sources were PubMed, Web of Science, EBSCO, SciVerse Scopus, SpringerLink, SciELO and DOAJ. The eligibility criteria considered were studies assessing exposure to OP pesticides and neurodevelopmental effects in children from birth to 18 years of age, published between 2002 and 2012 in English or Spanish. Twenty-seven articles met the eligibility criteria. Studies were rated for evidential consideration as high, intermediate, or low based upon the study design, number of participants, exposure measurement, and neurodevelopmental measures. All but one of the 27 studies evaluated showed some negative effects of pesticides on neurobehavioral development. A positive dose–response relationship between OP exposure and neurodevelopmental outcomes was found in all but one of the 12 studies that assessed dose–response. In the ten longitudinal studies that assessed prenatal exposure to OPs, cognitive deficits (related to working memory) were found in children at age 7 years, behavioral deficits (related to attention) seen mainly in toddlers, and motor deficits (abnormal reflexes) seen mainly in neonates. No meta-analysis was possible due to different measurements of exposure assessment and outcomes. Eleven studies (all longitudinal) were rated high, 14 studies were rated intermediate, and two studies were rated low. Evidence of neurological deficits associated with exposure to OP pesticides in children is growing. The studies reviewed collectively support the hypothesis that exposure to OP pesticides induces neurotoxic effects. Further research is needed to understand effects associated with exposure in critical windows of development.",
"title": "Neurodevelopmental effects in children associated with exposure to organophosphate pesticides: A systematic review"
},
{
"docid": "MED-1147",
"text": "The main sources of cadmium (Cd) input to soils have been phosphate fertilizers and deposition from air. In organic farming, phosphate fertilizers are not used, which may in the long term result in lower Cd levels. In the present study, feed, kidney, liver, and manure from growing/finishing pigs raised conventionally and organically on the same farm were microwave-digested and analyzed for Cd by graphite furnace atomic absorption spectrometry. Cd was also analyzed in soil and water. A quality control program was included. The organic pigs (n = 40) were raised outdoors and fed an organic feed; the conventional pigs (n = 40) were raised indoors and given a conventional feed. The Cd levels in organic and conventional feed were 39.9 microg/kg and 51.8 microg/kg, respectively. Organic feed contained 2% potato protein, which contributed 17% of the Cd content. Conventional feed contained 5% beet fiber, which contributed 38% of total Cd content. Both feeds contained vitamin-mineral mixtures with high levels of Cd: 991 microg/kg in organic and 589 microg/kg in conventional feed. There was a significant negative linear relationship between Cd concentration in kidney and kidney weight. There was no significant difference in liver Cd levels between organic and conventional pigs and the mean +/- SD was 15.4 +/- 3.0. In spite of the lower level of Cd in the organic feed, the organic pigs had significantly higher levels in kidneys than the conventional pigs, 96.1 +/- 19.5 microg/kg wet weight (mean +/- SD; n = 37) and 84.0 +/- 17.6 microg/kg wet weight (n = 40), respectively. Organic pigs had higher Cd levels in manure, indicating a higher Cd exposure from the environment, such as ingestion of soil. Differences in feed compositions and bioavailability of Cd from the feed components may also explain the different kidney levels of Cd.",
"title": "Cadmium in organic and conventional pig production."
},
{
"docid": "MED-2769",
"text": "The authors investigated whether early-life residency in certain areas of Iceland marked by distinct differences in milk intake was associated with risk of prostate cancer in a population-based cohort of 8,894 men born between 1907 and 1935. Through linkage to cancer and mortality registers, the men were followed for prostate cancer diagnosis and mortality from study entry (in waves from 1967 to 1987) through 2009. In 2002–2006, a subgroup of 2,268 participants reported their milk intake in early, mid-, and current life. During a mean follow-up period of 24.3 years, 1,123 men were diagnosed with prostate cancer, including 371 with advanced disease (stage 3 or higher or prostate cancer death). Compared with early-life residency in the capital area, rural residency in the first 20 years of life was marginally associated with increased risk of advanced prostate cancer (hazard ratio = 1.29, 95% confidence interval (CI): 0.97, 1.73), particularly among men born before 1920 (hazard ratio = 1.64, 95% CI: 1.06, 2.56). Daily milk consumption in adolescence (vs. less than daily), but not in midlife or currently, was associated with a 3.2-fold risk of advanced prostate cancer (95% CI: 1.25, 8.28). These data suggest that frequent milk intake in adolescence increases risk of advanced prostate cancer.",
"title": "Milk Intake in Early Life and Risk of Advanced Prostate Cancer"
},
{
"docid": "MED-1143",
"text": "Consumer choice between organically (without pesticides) and conventionally grown produce is examined. Exploratory focus-group discussions and questionnaires (N = 43) suggest that individuals who purchase organically grown produce believe it is substantially less hazardous than the conventional alternative and are willing to pay significant premiums to obtain it (a median 50% above the cost of conventional produce). The value of risk reduction implied by this incremental willingness to pay is not high relative to estimates for other risks, since the perceived risk reduction is relatively large. Organic-produce consumers also appear more likely than conventional-produce consumers to mitigate other ingestion-related risks (e.g., contaminated drinking water) but less likely to use automobile seatbelts.",
"title": "Risk perceptions and food choice: an exploratory analysis of organic- versus conventional-produce buyers."
},
{
"docid": "MED-1174",
"text": "We used a novel study design to measure dietary organophosphorus pesticide exposure in a group of 23 elementary school-age children through urinary biomonitoring. We substituted most of children’s conventional diets with organic food items for 5 consecutive days and collected two spot daily urine samples, first-morning and before-bedtime voids, throughout the 15-day study period. We found that the median urinary concentrations of the specific metabolites for malathion and chlorpyrifos decreased to the nondetect levels immediately after the introduction of organic diets and remained nondetectable until the conventional diets were reintroduced. The median concentrations for other organophosphorus pesticide metabolites were also lower in the organic diet consumption days; however, the detection of those metabolites was not frequent enough to show any statistical significance. In conclusion, we were able to demonstrate that an organic diet provides a dramatic and immediate protective effect against exposures to organophosphorus pesticides that are commonly used in agricultural production. We also concluded that these children were most likely exposed to these organophosphorus pesticides exclusively through their diet. To our knowledge, this is the first study to employ a longitudinal design with a dietary intervention to assess children’s exposure to pesticides. It provides new and persuasive evidence of the effectiveness of this intervention.",
"title": "Organic Diets Significantly Lower Children’s Dietary Exposure to Organophosphorus Pesticides"
},
{
"docid": "MED-4156",
"text": "The Gerson regimen, developed by Max Gerson in the 1930s, is promoted as an alternative cancer treatment. It involves consuming fresh, raw fruit and vegetable juices, eliminating salt from the diet, taking supplements such as potassium, vitamin B12, thyroid hormone, pancreatic enzymes, and detoxifying liver with coffee enemas to stimulate metabolism. Gerson therapy is based on the theory that cancer is caused by alteration of cell metabolism by toxic environmental substances and processed food, which changes its sodium and potassium content. It emphasizes increasing potassium intake and minimizing sodium consumption in an effort to correct the electrolyte imbalance, repair tissue, and detoxify the liver. The coffee enemas are believed to cause dilation of bile ducts and excretion of toxic breakdown products by the liver and through the colon wall. None of these theories has been substantiated by scientific research. Despite proponents' claims of recovery rates as high as 70% to 90%, case reviews by the National Cancer Institute (NCI) and the New York County Medical Society found no evidence of usefulness for the Gerson diet. An NCI-sponsored study of Gonzalez therapy, which is similar to the Gerson diet, showed that patients with inoperable pancreatic adenocarcinoma who underwent standard chemotherapy with gemcitabine (Gemzar) survived three times longer and had better quality of life than those who chose enzyme treatment, which included pancreatic enzymes, nutritional supplements, detoxification, and an organic diet.",
"title": "Gerson regimen."
},
{
"docid": "MED-1752",
"text": "The transforming growth factor-beta (TGF-beta) superfamily encompasses a large group of growth and differentiation factors playing important roles in regulating embryonic development and in maintaining tissue homeostasis in adult animals. Using degenerate polymerase chain reaction, we have identified a new murine TGF-beta family member, growth/differentiation factor-8 (GDF-8), which is expressed specifically in developing and adult skeletal muscle. During early stages of embryogenesis, GDF-8 expression is restricted to the myotome compartment of developing somites. At later stages and in adult animals, GDF-8 is expressed in many different muscles throughout the body. To determine the biological function of GDF-8, we disrupted the GDF-8 gene by gene targeting in mice. GDF-8 null animals are significantly larger than wild-type animals and show a large and widespread increase in skeletal muscle mass. Individual muscles of mutant animals weigh 2-3 times more than those of wild-type animals, and the increase in mass appears to result from a combination of muscle cell hyperplasia and hypertrophy. These results suggest that GDF-8 functions specifically as a negative regulator of skeletal muscle growth.",
"title": "Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member."
},
{
"docid": "MED-2461",
"text": "This study aimed to evaluate the association of diet with respiratory symptoms and asthma in schoolchildren in Taipei, Taiwan. An in-class interview survey elicited experiences of asthma and respiratory symptoms and consumption frequencies of the major food categories in 2290 fifth graders. Respiratory symptoms surveyed included persistent cough, chest tightness, wheezing with cold, wheezing without cold, dyspnea-associated wheezing, and exercise-induced cough or wheezing. Results showed that the consumption of sweetened beverages had the strongest association with respiratory symptoms and was positively associated with six of the seven respiratory symptoms (all p < 0.05). The adjusted odds ratios (aOR) ranged from 1.05 (95% confidence interval (CI = 1.01-1.09) for exercise-induced cough to 1.09 (95% CI = 1.03-1.16) for wheezing without cold. Egg consumption was associated with 5 of the 7 respiratory symptoms. Consumptions of seafood, soy products, and fruits were each negatively associated with one of the seven respiratory symptoms (all p < 0.05). Consumption of seafood was negatively associated with physician-diagnosed asthma and consumptions of sweetened beverages and eggs were positively associated with suspected asthma (p < 0.05). In conclusion, the study suggests that diet is associated with the respiratory symptoms in schoolchildren in Taipei. Consumptions of sweetened beverages and eggs are associated with increased risk of respiratory symptoms and asthma whereas consumptions of soy products and fruits are associated with reduced risk of respiratory symptoms.",
"title": "The association of diet with respiratory symptoms and asthma in schoolchildren in Taipei, Taiwan."
},
{
"docid": "MED-1149",
"text": "Background Lifestyle, dietary patterns and nutritional status of organic food consumers have rarely been described, while interest for a sustainable diet is markedly increasing. Methods Consumer attitude and frequency of use of 18 organic products were assessed in 54,311 adult participants in the Nutrinet-Santé cohort. Cluster analysis was performed to identify behaviors associated with organic product consumption. Socio-demographic characteristics, food consumption and nutrient intake across clusters are provided. Cross-sectional association with overweight/obesity was estimated using polytomous logistic regression. Results Five clusters were identified: 3 clusters of non-consumers whose reasons differed, occasional (OCOP, 51%) and regular (RCOP, 14%) organic product consumers. RCOP were more highly educated and physically active than other clusters. They also exhibited dietary patterns that included more plant foods and less sweet and alcoholic beverages, processed meat or milk. Their nutrient intake profiles (fatty acids, most minerals and vitamins, fibers) were healthier and they more closely adhered to dietary guidelines. In multivariate models (after accounting for confounders, including level of adherence to nutritional guidelines), compared to those not interested in organic products, RCOP participants showed a markedly lower probability of overweight (excluding obesity) (25≤body mass index<30) and obesity (body mass index ≥30): −36% and −62% in men and −42% and −48% in women, respectively (P<0.0001). OCOP participants (%) generally showed intermediate figures. Conclusions Regular consumers of organic products, a sizeable group in our sample, exhibit specific socio-demographic characteristics, and an overall healthy profile which should be accounted for in further studies analyzing organic food intake and health markers.",
"title": "Profiles of Organic Food Consumers in a Large Sample of French Adults: Results from the Nutrinet-Santé Cohort Study"
},
{
"docid": "MED-2469",
"text": "The intestinal flora is considered to have an impact on the development of the immune system. In the anthroposophic lifestyle, a diet comprising vegetables spontaneously fermented by lactobacilli, and a restrictive use of antibiotics, anti-pyretics and vaccinations, is typical. The aim of this study was to assess the gut flora in infants in relation to certain lifestyle characteristics associated with anthroposophy. Sixty-nine children < 2 years of age with an anthroposophic lifestyle, and 59 infants of a similar age with a traditional lifestyle, were clinically examined and questionnaire replies assessed. Fecal samples were analyzed by bacterial enumeration, bacterial typing through biochemical fingerprinting and by measuring microflora-associated characteristics (MACs). The numbers of colony-forming units (CFU)/g of feces were significantly higher for enterococci and lactic acid bacteria in children who had never been exposed to antibiotics (5.5 x 107 vs. 2.1 x 107; p < 0.001 and 10 x 107 vs. 4.1 x 107; p < 0.01, respectively). Furthermore, the number of enterococci was significantly higher in breastfed and vegetarian infants (p < 0.01). The diversity (Simpson's diversity index) of lactobacilli, as determined by biochemical fingerprinting, was higher in infants born at home than in those born in hospital (p < 0.01). Several MACs were related to specific lifestyle features, and infants with an anthroposophic lifestyle had a higher proportion of acetic acid and a lower proportion of propionic acid in their stool as compared to the control children. In conclusion, lifestyle factors related to the anthroposophic way of life influenced the composition of the gut flora in the infants. These differences may contribute to the lower prevalence of atopic disease previously observed in children in anthroposophic families.",
"title": "An anthroposophic lifestyle and intestinal microflora in infancy."
},
{
"docid": "MED-4137",
"text": "Swine have been identified as the primary reservoir of pathogenic Yersinia enterocolitica (YE), but little research has focused on the epidemiology of YE at the farm level. The objective of this study was to describe the prevalence of YE in different production phases on swine farms. In this cross-sectional study, individual pigs on eight swine operations were sampled for the presence of YE. On each farm, both feces and oral-pharyngeal swabs were collected from pigs in five different production phases: gestating, farrowing, suckling, nursery, and finishing. A pig was considered positive if either sample tested positive. Samples were cultured with cold enrichment followed by isolation on selective media plates. Presumptive isolates were confirmed as YE and assayed for the presence of ail with a multiplex PCR. Of the 2,349 pigs sampled, 120 (5.1%) tested positive, and of those, 51 were ail positive (42.5% of YE isolates). On all farms, there was a trend of increasing prevalence as pigs mature. Less than 1% of suckling piglets tested positive for YE. Only 1.4% (44.4% of which were ail positive) of nursery pigs tested positive, but 10.7% (48.1% of which were ail positive) of finishing pigs harbored YE. Interestingly, gestating sows had the second highest prevalence of YE at 9.1% (26.7% of which were ail positive), yet YE was never detected from the farrowing sows. These results represent the first on-farm description of YE in U.S. herds and provide the initial step for designing future studies of YE.",
"title": "Prevalence of Yersinia enterocolitica in different phases of production on swine farms."
},
{
"docid": "MED-4176",
"text": "Perfluorooctanesulfonylfluoride (POSF)-based compounds have been manufactured and used in a variety of industrial applications. These compounds degrade to perfluorooctanesulfonate (PFOS) which is regarded as a persistent end-stage metabolite and is found to accumulate in tissues of humans and wildlife. PFOS, perfluorohexanesulfonate (PFHxS), perfluorooctanoate (PFOA), and perfluorooctanesulfonamide (PFOSA) have been found in human sera from the United States. In this study, concentrations of PFHxS, perfluorobutanesulfonate (PFBS), PFOS, perfluorohexanoic acid (PFHxA), PFOA, perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorododecanoic acid (PFDoDA), and PFOSA were measured in 85 samples of whole human blood collected from nine cities (eight provinces) in China, including Shenyang (Liaoning), Beijing (Hebei), Zhengzhou (Henan), Jintan (Jiangsu), Wuhan (Hubei), Zhoushan (Zhejiang), Guiyang (Guizhou), Xiamen (Fujian), and Fuzhou (Fujian). Among the 10 perfluorinated compounds (PFCs) measured, PFOS was the predominant compound. The mean concentration of PFOS was greatest in samples collected from Shenyang (79.2 ng/mL) and least in samples from Jintan (3.72 ng/mL). PFHxS was the next most abundant perfluorochemical in the samples. No age-related differences in the concentrations of PFOA, PFOS, PFOSA, and PFHxS were observed. Gender-related differences were found,with males higher for PFOS and PFHxS, and females higher in PFUnDA. Concentrations of PFHxS were positively correlated with those of PFOS, while concentrations of PFNA, PFDA, and PFUnDA were positively correlated with those of PFOA. There were differences in the concentration profiles (percentage composition) of various PFCs in the samples among the nine cities.",
"title": "Perfluorooctanesulfonate and related fluorochemicals in human blood samples from China."
},
{
"docid": "MED-1740",
"text": "To assess human health risk from environmental chemicals, we have studied the effect on cell cycle regulation of the widely used glyphosate-containing pesticide Roundup. As a model system we have used sea urchin embryonic first divisions following fertilization, which are appropriate for the study of universal cell cycle regulation without interference with transcription. We show that 0.8% Roundup (containing 8 mM glyphosate) induces a delay in the kinetic of the first cell cleavage of sea urchin embryos. The delay is dependent on the concentration of Roundup. The delay in the cell cycle could be induced using increasing glyphosate concentrations (1-10 mM) in the presence of a subthreshold concentration of Roundup 0.2%, while glyphosate alone was ineffective, thus indicating synergy between glyphosate and Roundup formulation products. The effect of Roundup was not lethal and involved a delay in entry into M-phase of the cell cycle, as judged cytologically. Since CDK1/cyclin B regulates universally the M-phase of the cell cycle, we analyzed CDK1/cyclin B activation during the first division of early development. Roundup delayed the activation of CDK1/cyclin B in vivo. Roundup inhibited also the global protein synthetic rate without preventing the accumulation of cyclin B. In summary, Roundup affects cell cycle regulation by delaying activation of the CDK1/cyclin B complex, by synergic effect of glyphosate and formulation products. Considering the universality among species of the CDK1/cyclin B regulator, our results question the safety of glyphosate and Roundup on human health.",
"title": "Pesticide Roundup provokes cell division dysfunction at the level of CDK1/cyclin B activation."
},
{
"docid": "MED-1736",
"text": "Glyphosate is a herbicide widely used to kill weeds both in agricultural and non-agricultural landscapes. Its reproductive toxicity is related to the inhibition of a StAR protein and an aromatase enzyme, which causes an in vitro reduction in testosterone and estradiol synthesis. Studies in vivo about this herbicide effects in prepubertal Wistar rats reproductive development were not performed at this moment. Evaluations included the progression of puberty, body development, the hormonal production of testosterone, estradiol and corticosterone, and the morphology of the testis. Results showed that the herbicide (1) significantly changed the progression of puberty in a dose-dependent manner; (2) reduced the testosterone production, in semineferous tubules' morphology, decreased significantly the epithelium height (P < 0.001; control = 85.8 +/- 2.8 microm; 5 mg/kg = 71.9 +/- 5.3 microm; 50 mg/kg = 69.1 +/- 1.7 microm; 250 mg/kg = 65.2 +/- 1.3 microm) and increased the luminal diameter (P < 0.01; control = 94.0 +/- 5.7 microm; 5 mg/kg = 116.6 +/- 6.6 microm; 50 mg/kg = 114.3 +/- 3.1 microm; 250 mg/kg = 130.3 +/- 4.8 microm); (4) no difference in tubular diameter was observed; and (5) relative to the controls, no differences in serum corticosterone or estradiol levels were detected, but the concentrations of testosterone serum were lower in all treated groups (P < 0.001; control = 154.5 +/- 12.9 ng/dL; 5 mg/kg = 108.6 +/- 19.6 ng/dL; 50 mg/dL = 84.5 +/- 12.2 ng/dL; 250 mg/kg = 76.9 +/- 14.2 ng/dL). These results suggest that commercial formulation of glyphosate is a potent endocrine disruptor in vivo, causing disturbances in the reproductive development of rats when the exposure was performed during the puberty period.",
"title": "Prepubertal exposure to commercial formulation of the herbicide glyphosate alters testosterone levels and testicular morphology."
},
{
"docid": "MED-1754",
"text": "Conspiracist ideation has been repeatedly implicated in the rejection of scientific propositions, although empirical evidence to date has been sparse. A recent study involving visitors to climate blogs found that conspiracist ideation was associated with the rejection of climate science and the rejection of other scientific propositions such as the link between lung cancer and smoking, and between HIV and AIDS (Lewandowsky et al., in press; LOG12 from here on). This article analyses the response of the climate blogosphere to the publication of LOG12. We identify and trace the hypotheses that emerged in response to LOG12 and that questioned the validity of the paper’s conclusions. Using established criteria to identify conspiracist ideation, we show that many of the hypotheses exhibited conspiratorial content and counterfactual thinking. For example, whereas hypotheses were initially narrowly focused on LOG12, some ultimately grew in scope to include actors beyond the authors of LOG12, such as university executives, a media organization, and the Australian government. The overall pattern of the blogosphere’s response to LOG12 illustrates the possible role of conspiracist ideation in the rejection of science, although alternative scholarly interpretations may be advanced in the future.",
"title": "Recursive Fury: Conspiracist Ideation in the Blogosphere in Response to Research on Conspiracist Ideation"
},
{
"docid": "MED-2490",
"text": "Background: Rice can be a major source of inorganic arsenic (Asi) for many sub-populations. Rice products are also used as ingredients in prepared foods, some of which may not be obviously rice based. Organic brown rice syrup (OBRS) is used as a sweetener in organic food products as an alternative to high-fructose corn syrup. We hypothesized that OBRS introduces As into these products. Objective: We determined the concentration and speciation of As in commercially available brown rice syrups and in products containing OBRS, including toddler formula, cereal/energy bars, and high-energy foods used by endurance athletes. Methods: We used inductively coupled plasma mass spectrometry (ICP-MS) and ion chromatography coupled to ICP-MS to determine total As (Astotal) concentrations and As speciation in products purchased via the Internet or in stores in the Hanover, New Hampshire, area. Discussion: We found that OBRS can contain high concentrations of Asi and dimethyl-arsenate (DMA). An “organic” toddler milk formula containing OBRS as the primary ingredient had Astotal concentrations up to six times the U.S. Environmental Protection Agency safe drinking water limit. Cereal bars and high-energy foods containing OBRS also had higher As concentrations than equivalent products that did not contain OBRS. Asi was the main As species in most food products tested in this study. Conclusions: There are currently no U.S. regulations applicable to As in food, but our findings suggest that the OBRS products we evaluated may introduce significant concentrations of Asi into an individual’s diet. Thus, we conclude that there is an urgent need for regulatory limits on As in food.",
"title": "Arsenic, Organic Foods, and Brown Rice Syrup"
},
{
"docid": "MED-1596",
"text": "Recent observed feminization of aquatic animals has raised concerns about estrogenic compounds in water supplies and the potential for these chemicals to reach drinking water. Public perception frequently attributes this feminization to oral contraceptives (OCs) in wastewater and raises concerns that exposure to OCs in drinking water may contribute to the recent rise in human reproductive problems. This paper reviews the literature regarding various sources of estrogens, in surface, source and drinking water, with an emphasis on the active molecule that comes from OCs. It includes discussion of the various agricultural, industrial, and municipal sources and outlines the contributions of estrogenic chemicals to the estrogenicity of waterways and estimates that the risk of exposure to synthetic estrogens in drinking water on human health is negligible. This paper also provides recommendations for strategies to better understand all the potential sources of estrogenic compounds in the environment and possibilities to reduce the levels of estrogenic chemicals in the water supply.",
"title": "Are oral contraceptives a significant contributor to the estrogenicity of drinking water?"
},
{
"docid": "MED-1743",
"text": "This article describes the nutrient and elemental composition, including residues of herbicides and pesticides, of 31 soybean batches from Iowa, USA. The soy samples were grouped into three different categories: (i) genetically modified, glyphosate-tolerant soy (GM-soy); (ii) unmodified soy cultivated using a conventional \"chemical\" cultivation regime; and (iii) unmodified soy cultivated using an organic cultivation regime. Organic soybeans showed the healthiest nutritional profile with more sugars, such as glucose, fructose, sucrose and maltose, significantly more total protein, zinc and less fibre than both conventional and GM-soy. Organic soybeans also contained less total saturated fat and total omega-6 fatty acids than both conventional and GM-soy. GM-soy contained high residues of glyphosate and AMPA (mean 3.3 and 5.7 mg/kg, respectively). Conventional and organic soybean batches contained none of these agrochemicals. Using 35 different nutritional and elemental variables to characterise each soy sample, we were able to discriminate GM, conventional and organic soybeans without exception, demonstrating \"substantial non-equivalence\" in compositional characteristics for 'ready-to-market' soybeans. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.",
"title": "Compositional differences in soybeans on the market: glyphosate accumulates in Roundup Ready GM soybeans."
},
{
"docid": "MED-4135",
"text": "Yersinia enterocolitica are ubiquitous, being isolated frequently from soil, water, animals, and a variety of foods. They comprise a biochemically heterogeneous group that can survive and grow at refrigeration temperatures. The ability to propagate at refrigeration temperatures is of considerable significance in food hygiene. Virulent strains of Yersinia invade mammalian cells such as HeLa cells in tissue culture. Two chromosomal genes, inv and ail, were identified for cell invasion of mammalian. The pathogen can cause diarrhoea, appendicitis and post-infection arthritis may occur in a small proportion of cases. The most common transmission route of pathogenic Y. enterocolitica is thought to be fecal-oral via contaminated food. Direct person-to-person contact is rare. Occasionally, pathogenic Y. enterocolitica has been detected in vegetables and environmental water; thus, vegetables and untreated water are also potential sources of human yersiniosis. However, the isolation rates of pathogenic Y. enterocolitica have been low, which may be due to the limited sensitivity of the detection methods. To identify other possible transmission vehicles, different food items should be studied more extensively. Many factors related to the epidemiology of Y. enterocolitica, such as sources, transmission routes, and predominating genotypes remain obscure because of the low sensitivity of detection methods.",
"title": "Behavior of Yersinia enterocolitica in Foods"
},
{
"docid": "MED-4090",
"text": "Apple peel is a waste product from dried apple manufacture. The content of phenolic compounds, dietary fiber, and mineral are higher in apple peel, compared to other edible parts of this fruits. The objective of this study was to develop an ingredient from Granny Smith apple peel, using a pilot scale double drum-dryer, as drying technology. The control of all steps to maximize the retention of phenolic compounds and dietary fiber was considered. Operational conditions, such as drying temperature and time were determined, as well as important preprocessing steps like grinding and PPO inhibition. In addition, the physical-chemical characteristics, mineral and sugar content, and technological functional properties such as water retention capacity, solubility index, and dispersability among others, were analyzed. A simple, economical, and suitable pilot scale process, to produce a powder ingredient from apple peel by-product, was obtained. The drying process includes the application of ascorbic acid at 0.5% in the fresh apple peel slurry, drum-dryer operational conditions were 110 degrees C, 0.15 rpm and 0.2 mm drum clearance. The ingredient developed could be considered as a source of phenolic compounds (38.6 mg gallic acid equivalent/g dry base) and dietary fiber (39.7% dry base) in the formulation of foods. Practical Application: A method to develop an ingredient from Granny Smith apple peel using a pilot scale double drum-dryer as drying technology was developed. The method is simple, economical, feasible, and suitable and maximizes the retention of phenolic compounds and dietary fiber present in the raw matter. The ingredient could be used in the formulation of foods.",
"title": "Development of an ingredient containing apple peel, as a source of polyphenols and dietary fiber."
},
{
"docid": "MED-1750",
"text": "The discovery of myostatin and our introduction to the “Mighty Mouse” over a decade ago spurred both basic and applied research and impacted popular culture as well. The myostatin-null genotype produces “double muscling” in mice and livestock and was recently described in a child. The field’s rapid growth is by no means surprising considering the potential benefits of enhancing muscle growth in clinical and agricultural settings. Indeed, several recent studies suggest that blocking myostatin’s inhibitory effects could improve the clinical treatment of several muscle growth disorders, whereas comparative studies suggest that these actions are at least partly conserved. Thus, neutralizing myostatin’s effects could also have agricultural significance. Extrapolating between studies that use different vertebrate models, particularly fish and mammals, is somewhat confusing because whole genome duplication events have resulted in the production and retention of up to four unique myostatin genes in some fish species. Such comparisons, however, suggest that myostatin’s actions may not be limited to skeletal muscle per se, but may additionally influence other tissues including cardiac muscle, adipocytes, and the brain. Thus, therapeutic intervention in the clinic or on the farm must consider the potential of alternative side effects that could impact these or other tissues. In addition, the presence of multiple and actively diversifying myostatin genes in most fish species provides a unique opportunity to study adaptive molecular evolution. It may also provide insight into myostatin’s nonmuscle actions as results from these and other comparative studies gain visibility in biomedical fields.",
"title": "Clinical, Agricultural, and Evolutionary Biology of Myostatin: A Comparative Review"
},
{
"docid": "MED-5071",
"text": "Dietary intervention with anthocyanins may confer benefits in brain function, including vision. Research to date indicates that animals have only a limited capacity to absorb anthocyanins, compared to other types of flavonoids. Pigs, which are a suitable model for human digestive absorption, were used to examine the deposition of anthocyanins in tissues including the liver, eye, and brain tissue. Pigs were fed diets supplemented with 0, 1, 2, or 4% w/w blueberries ( Vaccinium corymbosum L. 'Jersey') for 4 weeks. Prior to euthanasia, pigs were fasted for 18-21 h. Although no anthocyanins were detected in the plasma or urine of the fasted animals, intact anthocyanins were detected in all tissues where they were sought. LC-MS/MS results are presented for the relative concentration of 11 intact anthocyanins in the liver, eye, cortex, and cerebellum. The results suggest that anthocyanins can accumulate in tissues, including tissues beyond the blood-brain barrier.",
"title": "Identification of anthocyanins in the liver, eye, and brain of blueberry-fed pigs."
},
{
"docid": "MED-1741",
"text": "Roundup is a glyphosate-based herbicide used worldwide, including on most genetically modified plants that have been designed to tolerate it. Its residues may thus enter the food chain, and glyphosate is found as a contaminant in rivers. Some agricultural workers using glyphosate have pregnancy problems, but its mechanism of action in mammals is questioned. Here we show that glyphosate is toxic to human placental JEG3 cells within 18 hr with concentrations lower than those found with agricultural use, and this effect increases with concentration and time or in the presence of Roundup adjuvants. Surprisingly, Roundup is always more toxic than its active ingredient. We tested the effects of glyphosate and Roundup at lower nontoxic concentrations on aromatase, the enzyme responsible for estrogen synthesis. The glyphosate-based herbicide disrupts aromatase activity and mRNA levels and interacts with the active site of the purified enzyme, but the effects of glyphosate are facilitated by the Roundup formulation in microsomes or in cell culture. We conclude that endocrine and toxic effects of Roundup, not just glyphosate, can be observed in mammals. We suggest that the presence of Roundup adjuvants enhances glyphosate bioavailability and/or bioaccumulation.",
"title": "Differential Effects of Glyphosate and Roundup on Human Placental Cells and Aromatase"
},
{
"docid": "MED-2775",
"text": "The incidence and mortality rates of testicular and prostatic cancers in 42 countries were correlated with the dietary practices in these countries using the cancer rates (1988-92) provided by the International Agency for Research on Cancer (IARC) and the food supply data (1961-90) provided by the Food and Agriculture Organization (FAO). Among the food items we examined, cheese was most closely correlated with the incidence of testicular cancer at ages 20-39, followed by animal fats and milk. The correlation coefficient (r) was highest (r = 0.804) when calculated for cheese consumed during the period 1961-65 (maternal or prepubertal consumption). Stepwise-multiple-regression analysis revealed that milk + cheese (1961-65) made a significant contribution to the incidence of testicular cancer (standardized regression coefficient [R] = 0.654). Concerning prostatic cancer, milk (1961-90) was most closely correlated (r = 0.711) with its incidence, followed by meat and coffee. Stepwise-multiple-regression analysis identified milk + cheese as a factor contributing to the incidence of prostatic cancer (R = 0.525). The food that was most closely correlated with the mortality rate of prostatic cancer was milk (r = 0.766), followed by coffee, cheese and animal fats. Stepwise-multiple-regression analysis revealed that milk + cheese was a factor contributing to mortality from prostatic cancer (R = 0.580). The results of our study suggest a role of milk and dairy products in the development and growth of testicular and prostatic cancers. The close correlation between cheese and testicular cancer and between milk and prostatic cancer suggests that further mechanistic studies should be undertaken concerning the development of male genital organ cancers. Copyright 2001 Wiley-Liss, Inc.",
"title": "Incidence and mortality of testicular and prostatic cancers in relation to world dietary practices."
},
{
"docid": "MED-3880",
"text": "A common approach to reducing microbial contamination has been the implementation of a Hazard Analysis and Critical Control Point (HACCP) program to prevent or reduce contamination during production. One example is the Pathogen Reduction HACCP program implemented by the U.S. Department of Agriculture's Food Safety and Inspection Service (FSIS). This program consisted of a staged implementation between 1996 and 2000 to reduce microbial contamination on meat and poultry products. Of the commodities regulated by FSIS, one of the largest observed reductions was for Salmonella contamination on broiler chicken carcasses. Nevertheless, how this reduction might have influenced the total number of salmonellosis cases in the United States has not been assessed. This study incorporates information from public health surveillance and surveys of the poultry slaughter industry into a model that estimates the number of broiler-related salmonellosis cases through time. The model estimates that-following the 56% reduction in the proportion of contaminated broiler carcasses observed between 1995 and 2000-approximately 190,000 fewer annual salmonellosis cases (attributed to broilers) occurred in 2000 compared with 1995. The uncertainty bounds for this estimate range from approximately 37,000 to 500,000 illnesses. Estimated illnesses prevented, due to the more modest reduction in contamination of 13% between 2000 and 2007, were not statistically significant. An analysis relating the necessary magnitude of change in contamination required for detection via human surveillance also is provided.",
"title": "Estimating changes in public health following implementation of hazard analysis and critical control point in the United States broiler slaughter i..."
},
{
"docid": "MED-1179",
"text": "The US market for organic foods has grown from $3.5 billion in 1996 to $28.6 billion in 2010, according to the Organic Trade Association. Organic products are now sold in specialty stores and conventional supermarkets. Organic products contain numerous marketing claims and terms, only some of which are standardized and regulated. In terms of health advantages, organic diets have been convincingly demonstrated to expose consumers to fewer pesticides associated with human disease. Organic farming has been demonstrated to have less environmental impact than conventional approaches. However, current evidence does not support any meaningful nutritional benefits or deficits from eating organic compared with conventionally grown foods, and there are no well-powered human studies that directly demonstrate health benefits or disease protection as a result of consuming an organic diet. Studies also have not demonstrated any detrimental or disease-promoting effects from an organic diet. Although organic foods regularly command a significant price premium, well-designed farming studies demonstrate that costs can be competitive and yields comparable to those of conventional farming techniques. Pediatricians should incorporate this evidence when discussing the health and environmental impact of organic foods and organic farming while continuing to encourage all patients and their families to attain optimal nutrition and dietary variety consistent with the US Department of Agriculture's MyPlate recommendations. This clinical report reviews the health and environmental issues related to organic food production and consumption. It defines the term \"organic,\" reviews organic food-labeling standards, describes organic and conventional farming practices, and explores the cost and environmental implications of organic production techniques. It examines the evidence available on nutritional quality and production contaminants in conventionally produced and organic foods. Finally, this report provides guidance for pediatricians to assist them in advising their patients regarding organic and conventionally produced food choices.",
"title": "Organic foods: health and environmental advantages and disadvantages."
},
{
"docid": "MED-1140",
"text": "Consumer concern over the quality and safety of conventional food has intensified in recent years, and primarily drives the increasing demand for organically grown food, which is perceived as healthier and safer. Relevant scientific evidence, however, is scarce, while anecdotal reports abound. Although there is an urgent need for information related to health benefits and/or hazards of food products of both origins, generalized conclusions remain tentative in the absence of adequate comparative data. Organic fruits and vegetables can be expected to contain fewer agrochemical residues than conventionally grown alternatives; yet, the significance of this difference is questionable, inasmuch as actual levels of contamination in both types of food are generally well below acceptable limits. Also, some leafy, root, and tuber organic vegetables appear to have lower nitrate content compared with conventional ones, but whether or not dietary nitrate indeed constitutes a threat to human health is a matter of debate. On the other hand, no differences can be identified for environmental contaminants (e.g. cadmium and other heavy metals), which are likely to be present in food from both origins. With respect to other food hazards, such as endogenous plant toxins, biological pesticides and pathogenic microorganisms, available evidence is extremely limited preventing generalized statements. Also, results for mycotoxin contamination in cereal crops are variable and inconclusive; hence, no clear picture emerges. It is difficult, therefore, to weigh the risks, but what should be made clear is that 'organic' does not automatically equal 'safe.' Additional studies in this area of research are warranted. At our present state of knowledge, other factors rather than safety aspects seem to speak in favor of organic food.",
"title": "Organic food: buying more safety or just peace of mind? A critical review of the literature."
},
{
"docid": "MED-3886",
"text": "The treatment of bacterial infections is increasingly complicated by the ability of bacteria to develop resistance to antimicrobial agents. Antimicrobial agents are often categorized according to their principal mechanism of action. Mechanisms include interference with cell wall synthesis (e.g., beta-lactams and glycopeptide agents), inhibition of protein synthesis (macrolides and tetracyclines), interference with nucleic acid synthesis (fluoroquinolones and rifampin), inhibition of a metabolic pathway (trimethoprim-sulfamethoxazole), and disruption of bacterial membrane structure (polymyxins and daptomycin). Bacteria may be intrinsically resistant to > or =1 class of antimicrobial agents, or may acquire resistance by de novo mutation or via the acquisition of resistance genes from other organisms. Acquired resistance genes may enable a bacterium to produce enzymes that destroy the antibacterial drug, to express efflux systems that prevent the drug from reaching its intracellular target, to modify the drug's target site, or to produce an alternative metabolic pathway that bypasses the action of the drug. Acquisition of new genetic material by antimicrobial-susceptible bacteria from resistant strains of bacteria may occur through conjugation, transformation, or transduction, with transposons often facilitating the incorporation of the multiple resistance genes into the host's genome or plasmids. Use of antibacterial agents creates selective pressure for the emergence of resistant strains. Herein 3 case histories-one involving Escherichia coli resistance to third-generation cephalosporins, another focusing on the emergence of vancomycin-resistant Staphylococcus aureus, and a third detailing multidrug resistance in Pseudomonas aeruginosa--are reviewed to illustrate the varied ways in which resistant bacteria develop.",
"title": "Mechanisms of antimicrobial resistance in bacteria."
},
{
"docid": "MED-5056",
"text": "BACKGROUND: Oxidative damage is implicated in the etiology of cancer, cardiovascular disease, and other degenerative disorders. Recent nutritional research has focused on the antioxidant potential of foods, while current dietary recommendations are to increase the intake of antioxidant-rich foods rather than supplement specific nutrients. Many alternatives to refined sugar are available, including raw cane sugar, plant saps/syrups (eg, maple syrup, agave nectar), molasses, honey, and fruit sugars (eg, date sugar). Unrefined sweeteners were hypothesized to contain higher levels of antioxidants, similar to the contrast between whole and refined grain products. OBJECTIVE: To compare the total antioxidant content of natural sweeteners as alternatives to refined sugar. DESIGN: The ferric-reducing ability of plasma (FRAP) assay was used to estimate total antioxidant capacity. Major brands of 12 types of sweeteners as well as refined white sugar and corn syrup were sampled from retail outlets in the United States. RESULTS: Substantial differences in total antioxidant content of different sweeteners were found. Refined sugar, corn syrup, and agave nectar contained minimal antioxidant activity (<0.01 mmol FRAP/100 g); raw cane sugar had a higher FRAP (0.1 mmol/100 g). Dark and blackstrap molasses had the highest FRAP (4.6 to 4.9 mmol/100 g), while maple syrup, brown sugar, and honey showed intermediate antioxidant capacity (0.2 to 0.7 mmol FRAP/100 g). Based on an average intake of 130 g/day refined sugars and the antioxidant activity measured in typical diets, substituting alternative sweeteners could increase antioxidant intake an average of 2.6 mmol/day, similar to the amount found in a serving of berries or nuts. CONCLUSION: Many readily available alternatives to refined sugar offer the potential benefit of antioxidant activity.",
"title": "Total antioxidant content of alternatives to refined sugar."
},
{
"docid": "MED-1180",
"text": "The effects of extracts from five cultivars of strawberries on the proliferation of colon cancer cells HT29 and breast cancer cells MCF-7 were investigated, and possible correlations with the levels of several antioxidants were analyzed. In addition, the effects of organic cultivation compared to conventional cultivation on the content of antioxidants in the strawberries and strawberry extracts on the cancer cell proliferation were investigated. The ratio of ascorbate to dehydroascorbate was significantly higher in the organically cultivated strawberries. The strawberry extracts decreased the proliferation of both HT29 cells and MCF-7 cells in a dose-dependent way. The inhibitory effect for the highest concentration of the extracts was in the range of 41-63% (average 53%) inhibition compared to controls for the HT29 cells and 26-56% (average 43%) for MCF-7 cells. The extracts from organically grown strawberries had a higher antiproliferative activity for both cell types at the highest concentration than the conventionally grown, and this might indicate a higher content of secondary metabolites with anticarcinogenic properties in the organically grown strawberries. For HT29 cells, there was a negative correlation at the highest extract concentration between the content of ascorbate or vitamin C and cancer cell proliferation, whereas for MCF-7 cells, a high ratio of ascorbate to dehydroascorbate correlated with a higher inhibition of cell proliferation at the second highest concentration. The significance of the effect of ascorbate on cancer cell proliferation might lie in a synergistic action with other compounds.",
"title": "Antioxidant levels and inhibition of cancer cell proliferation in vitro by extracts from organically and conventionally cultivated strawberries."
},
{
"docid": "MED-3888",
"text": "BACKGROUND: Salmonella enterica causes an estimated 1 million cases of domestically acquired foodborne illness in humans annually in the United States; Enteritidis (SE) is the most common serotype. Public health authorities, regulatory agencies, food producers, and food processors need accurate information about rates and changes in SE infection to implement and evaluate evidence-based control policies and practices. METHODS: We analyzed the incidence of human SE infection during 1996-2009 in the Foodborne Diseases Active Surveillance Network (FoodNet), an active, population-based surveillance system for laboratory-confirmed infections. We compared FoodNet incidence with passively collected data from complementary surveillance systems and with rates of SE isolation from processed chickens and egg products; shell eggs are not routinely tested. We also compared molecular subtyping patterns of SE isolated from humans and chickens. RESULTS: Since the period 1996-1999, the incidence of human SE infection in FoodNet has increased by 44%. This change is mirrored in passive national surveillance data. The greatest relative increases were in young children, older adults, and FoodNet sites in the southern United States. The proportion of patients with SE infection who reported recent international travel has decreased in recent years, whereas the proportion of chickens from which SE was isolated has increased. Similar molecular subtypes of SE are commonly isolated from humans and chickens. CONCLUSIONS: Most SE infections in the United States are acquired from domestic sources, and the problem is growing. Chicken and eggs are likely major sources of SE. Continued close attention to surveillance data is needed to monitor the impact of recent regulatory control measures.",
"title": "Salmonella enterica serotype Enteritidis: increasing incidence of domestically acquired infections."
},
{
"docid": "MED-1739",
"text": "Glyphosate is the primary active constituent of the commercial pesticide Roundup. The present results show that acute Roundup exposure at low doses (36 ppm, 0.036 g/L) for 30 min induces oxidative stress and activates multiple stress-response pathways leading to Sertoli cell death in prepubertal rat testis. The pesticide increased intracellular Ca(2+) concentration by opening L-type voltage-dependent Ca(2+) channels as well as endoplasmic reticulum IP3 and ryanodine receptors, leading to Ca(2+) overload within the cells, which set off oxidative stress and necrotic cell death. Similarly, 30 min incubation of testis with glyphosate alone (36 ppm) also increased (45)Ca(2+) uptake. These events were prevented by the antioxidants Trolox and ascorbic acid. Activated protein kinase C, phosphatidylinositol 3-kinase, and the mitogen-activated protein kinases such as ERK1/2 and p38MAPK play a role in eliciting Ca(2+) influx and cell death. Roundup decreased the levels of reduced glutathione (GSH) and increased the amounts of thiobarbituric acid-reactive species (TBARS) and protein carbonyls. Also, exposure to glyphosate-Roundup stimulated the activity of glutathione peroxidase, glutathione reductase, glutathione S-transferase, γ-glutamyltransferase, catalase, superoxide dismutase, and glucose-6-phosphate dehydrogenase, supporting downregulated GSH levels. Glyphosate has been described as an endocrine disruptor affecting the male reproductive system; however, the molecular basis of its toxicity remains to be clarified. We propose that Roundup toxicity, implicated in Ca(2+) overload, cell signaling misregulation, stress response of the endoplasmic reticulum, and/or depleted antioxidant defenses, could contribute to Sertoli cell disruption in spermatogenesis that could have an impact on male fertility. Copyright © 2013 Elsevier Inc. All rights reserved.",
"title": "Roundup disrupts male reproductive functions by triggering calcium-mediated cell death in rat testis and Sertoli cells."
},
{
"docid": "MED-1161",
"text": "Pesticides are one of the major inputs used for increasing agricultural productivity of crops. The pesticide residues, left to variable extent in the food materials after harvesting, are beyond the control of consumer and have deleterious effect on human health. The presence of pesticide residues is a major bottleneck in the international trade of food commodities. The localization of pesticides in foods varies with the nature of pesticide molecule, type and portion of food material and environmental factors. The food crops treated with pesticides invariably contain unpredictable amount of these chemicals, therefore, it becomes imperative to find out some alternatives for decontamination of foods. The washing with water or soaking in solutions of salt and some chemicals e.g. chlorine, chlorine dioxide, hydrogen peroxide, ozone, acetic acid, hydroxy peracetic acid, iprodione and detergents are reported to be highly effective in reducing the level of pesticides. Preparatory steps like peeling, trimming etc. remove the residues from outer portions. Various thermal processing treatments like pasteurization, blanching, boiling, cooking, steaming, canning, scrambling etc. have been found valuable in degradation of various pesticides depending upon the type of pesticide and length of treatment. Preservation techniques like drying or dehydration and concentration increase the pesticide content many folds due to concentration effect. Many other techniques like refining, fermentation and curing have been reported to affect the pesticide level in foods to varied extent. Milling, baking, wine making, malting and brewing resulted in lowering of pesticide residue level in the end products. Post harvest treatments and cold storage have also been found effective. Many of the decontamination techniques bring down the concentration of pesticides below MRL. However, the diminution effect depends upon the initial concentration at the time of harvest, substrate/food and type of pesticide. There is diversified information available in literature on the effect of preparation, processing and subsequent handling and storage of foods on pesticide residues which has been compiled in this article.",
"title": "Effect of handling and processing on pesticide residues in food- a review"
},
{
"docid": "MED-2468",
"text": "BACKGROUND AND METHODS: We estimated the prevalence of self-reported asthma in adult Indians and examined several risk factors influencing disease prevalence. Analysis is based on 99 574 women and 56 742 men aged 20–49 years included in India’s third National Family Health Survey, 2005–2006. Multiple logistic regression analysis was used to estimate the prevalence odds ratios for asthma, adjusting for various risk factors. RESULTS: The prevalence of self-reported asthma was 1.8% (95%CI 1.6–2.0) among men and 1.9% (95%CI 1.8–2.0) among women, with higher rates in rural than in urban areas and marked geographic differences. After adjustment for known asthma risk factors, women were 1.2 times more likely to have asthma than men. Daily/weekly consumption of milk/milk products, green leafy vegetables and fruits were associated with a lower asthma risk, whereas consumption of chicken/meat, a lower body mass index (BMI; <16 kg/m2, OR 2.08, 95%CI 1.73–2.50) as well as a higher BMI (>30 kg/m2, OR 1.67, 95%CI 1.36–2.06), current tobacco smoking (OR 1.30, 95%CI 1.12–1.50) and ever use of alcohol (OR 1.21, 95%CI 1.05–1.39) were associated with an increased asthma risk. CONCLUSIONS: There are wide regional variations in the prevalence of asthma in India. With the exception of the findings for BMI, however, most of the associations of asthma with the risk factors are relatively weak and account for only a small proportion of cases. RÉSUMÉ CONTEXTE ET MÉTHODES: Nous avons estimé la prévalence auto-rapportée de l’asthme chez les Indiens adultes et examiné plusieurs facteurs de risque influençant la prévalence de la maladie. L’analyse repose sur 99 574 femmes et 56 742 hommes âgés de 20 à 49 ans et inclus dans la troisième Enquête Nationale des Familles en Inde, 2005–2006. On a utilisé l’analyse de régression logistique multiple pour estimer les odds ratio de prévalence pour l’asthme, après ajustement pour divers facteurs de risque. RÉSULTATS: La prévalence auto-rapportée de l’asthme est de 1,8% (IC95% 1,6–2,0) parmi les hommes et de 1,9% (IC95% 1,8–2,0) parmi les femmes, les taux étant plus élevés dans les zones rurales que dans les zones urbaines, et les différences géographiques étant marquées. Après ajustement pour les facteurs de risque d’asthme connus, les femmes sont 1,2 fois plus susceptibles de souffrir de l’asthme que les hommes. La consommation quotidienne ou hebdomadaire de lait/produits laitiers, de légumes à feuilles vertes et de fruits est en association avec un risque plus faible d’asthme alors que la consommation de poulet ou de viande, un index de masse corporelle (BMI) plus bas (<16 kg/m2, OR 2,08 ; IC95% 1,73–2,50) ainsi qu’un BMI plus élevé (>30 kg/m2, OR 1,67 ; IC95% 1,36–2,06), le fait de fumer du tabac actuellement (OR 1,30 ; IC95% 1,12–1,50) et l’utilisation de l’alcool à un moment quelconque (OR 1,21 ; IC95% 1,05–1,39) sont en association avec un risque accru d’asthme. La prévalence de l’asthme en Inde varie largement selon les régions. Toutefois, à l’exception des observations sur le BMI, l’association de l’asthme avec les facteurs de risque est relativement faible et ne rend compte que d’une petite proportion des cas seulement. RESUMEN MARCO DE REFERENCIA Y MÉTODOS: Se calculó la prevalencia de asma autorreferida en los adultos en la India y se evaluaron varios factores de riesgo que influyen sobre la prevalencia de la enfermedad. El estudio se basó en las 99 574 mujeres y los 56 742 hombres de 20 a 49 años de edad que participaron en la tercera Encuesta Nacional sobre la Salud de la Familia en la India entre el 2005 y el 2006. Mediante un análisis de regresión logística multifactorial se calculó la prevalencia de asma y el cociente de posibilidades de padecerla, al corregir diversos factores de riesgo. RESULTADOS: La prevalencia de asma autorreferida fue 1,8% en los hombres (intervalo de confianza [IC] del 95% 1,6 a 2,0) y 1,9% en las mujeres (IC95% 1,8 a 2,0); se observaron tasas más altas en las zonas rurales que en las zonas urbanas y se presentaron diferencias geográficas considerables. Tras corregir en función de algunos factores de riesgo de padecer asma conocidos, las mujeres presentaron una probabilidad 1,2 veces superior a los hombres de sufrir la enfermedad. El consumo diario o semanal de leche o productos lácteos, hortalizas de hojas verdes y frutas se asoció con un menor riesgo de asma y el consumo de carne de pollo o de res, un bajo índice de masa corporal (<16 kg/m2; OR 2,08; IC95% 1,73 a 2,50) igual que un alto índice de masa corporal (>30 kg/m2; OR 1,67; IC95% 1,36 a 2,06), el tabaquismo actual (OR 1,30; IC95% 1,12 a 1,50) y el consumo de alcohol en algún momento de la vida (OR 1,21; IC95% 1,05 a 1,39) se asociaron con un mayor riesgo de padecer la enfermedad. CONCLUSIÓN: Existen amplias variaciones geográficas en la prevalencia de asma en la India. Sin embargo, con la excepción del índice de masa corporal, la mayor parte de las asociaciones del asma con los factores de riesgo fueron débiles y explican solo una pequeña proporción de los casos.",
"title": "Prevalence and risk factors for self-reported asthma in an adult Indian population: a cross-sectional survey"
},
{
"docid": "MED-2899",
"text": "The present study was designed to assess the relationship between iris color and macular pigment optical density. Both melanin and carotenoids (responsible for iris color and macular pigment composition, respectively) appear to protect the retina through similar mechanisms and higher concentrations may reduce the incidence of retinal degenerations. To evaluate this relationship, 95 subjects were examined and the following variables were measured: iris color; macular pigment optical density (MP); plasma concentrations of lutein and zeaxanthin and beta-carotene; dietary intake of lutein and zeaxanthin and beta-carotene; and total fat intake. Iris color was determined by self assessment and classified as blue or gray (group I), green or hazel (group II) or brown or black (group III). MP density was measured psychophysically by measuring foveal and parafoveal sensitivities to lights of 460 and 550 nm, using the method of heterochromatic flicker photometry. Plasma carotenoid concentrations were measured using reverse-phase high-performance liquid chromatography. Dietary intake was determined by a detailed food-frequency questionnaire. Despite similarities in diet and in blood concentrations of carotenoids, significant differences in macular pigment density (P < 0.02) were found for different colored irises (group I, n = 38, MP = 0.25; group II, n = 26, MP = 0.32; group III, n = 31, MP = 0.38). The covariation of iris color and MP indicates that past epidemiologic studies have not adequately determined the independent effects of either factor. The relationship of MP and iris color may be the result of one or two factors: the evolution of a shared tendency to accumulate melanin and carotenoids due to similar environmental pressures (e.g. light and oxygen); and/or MP might be depleted due to the tendency for eyes with light irises to transmit more light than eyes with dark irises, thus causing increased oxidative stress.",
"title": "Iris color and macular pigment optical density."
},
{
"docid": "MED-1726",
"text": "Pesticides are used throughout the world as mixtures called formulations. They contain adjuvants, which are often kept confidential and are called inerts by the manufacturing companies, plus a declared active principle, which is usually tested alone. We tested the toxicity of 9 pesticides, comparing active principles and their formulations, on three human cell lines (HepG2, HEK293, and JEG3). Glyphosate, isoproturon, fluroxypyr, pirimicarb, imidacloprid, acetamiprid, tebuconazole, epoxiconazole, and prochloraz constitute, respectively, the active principles of 3 major herbicides, 3 insecticides, and 3 fungicides. We measured mitochondrial activities, membrane degradations, and caspases 3/7 activities. Fungicides were the most toxic from concentrations 300–600 times lower than agricultural dilutions, followed by herbicides and then insecticides, with very similar profiles in all cell types. Despite its relatively benign reputation, Roundup was among the most toxic herbicides and insecticides tested. Most importantly, 8 formulations out of 9 were up to one thousand times more toxic than their active principles. Our results challenge the relevance of the acceptable daily intake for pesticides because this norm is calculated from the toxicity of the active principle alone. Chronic tests on pesticides may not reflect relevant environmental exposures if only one ingredient of these mixtures is tested alone.",
"title": "Major Pesticides Are More Toxic to Human Cells Than Their Declared Active Principles"
},
{
"docid": "MED-4174",
"text": "Perfluorooctanesulfonyl fluoride based compounds have been used in a wide variety of consumer products, such as carpets, upholstery, and textiles. These compounds degrade to perfluorooctanesulfonate (PFOS), a persistent metabolite that accumulates in tissues of humans and wildlife. Previous studies have reported the occurrence of PFOS, perfluorohexanesulfonate (PFHxS), perfluorooctanoate (PFOA), and perfluorooctanesulfonamide (PFOSA) in human sera collected from the United States. In this study, concentrations of PFOS, PFHxS, PFOA, and PFOSA were measured in 473 human blood/serum/plasma samples collected from the United States, Colombia, Brazil, Belgium, Italy, Poland, India, Malaysia, and Korea. Among the four perfluorochemicals measured, PFOS was the predominant compound found in blood. Concentrations of PFOS were the highest in the samples collected from the United States and Poland (>30 ng/mL); moderate in Korea, Belgium, Malaysia, Brazil, Italy, and Colombia (3 to 29 ng/mL); and lowest in India (<3 ng/mL). PFOA was the next most abundant perfluorochemical in blood samples, although the frequency of occurrence of this compound was relatively low. No age- or gender-related differences in the concentrations of PFOS and PFOA were found in serum samples. The degree of association between the concentrations of four perfluorochemicals varied, depending on the origin of the samples. These results suggested the existence of sources with varying levels and compositions of perfluorochemicals, and differences in exposure patterns to these chemicals, in various countries. In addition to the four target fluorochemicals measured, qualitative analysis of selected blood samples showed the presence of other perfluorochemicals such as perfluorodecanesulfonate (PFDS), perfluoroheptanoic acid (PFHpA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluorododecanoic acid (PFDoA), and perfluoroundecanoic acid (PFUnDA) in serum samples, at concentrations approximately 5- to 10-fold lower than the concentration of PFOS. Further studies should focus on identifying sources and pathways of human exposure to perfluorochemicals.",
"title": "Perfluorooctanesulfonate and related fluorochemicals in human blood from several countries."
},
{
"docid": "MED-2472",
"text": "Thirty-five patients who had suffered from bronchial asthma for an average of 12 yr, all receiving long-term medication, 20 including cortisone, were subject to therapy with vegan food for 1 yr. In almost all cases, medication was withdrawn or drastically reduced. There was a significant decrease in asthma symptoms. Twenty-four patients (69%) fulfilled the treatment. Of these, 71% reported improvement at 4 months and 92% at 1 yr. There was a significant improvement in a number of clinical variables; for example, vital capacity, forced expiratory volume at one sec and physical working capacity, as well as a significant change in various biochemical indices as haptoglobin, IgM, IgE, cholesterol, and triglycerides in blood. Selected patients, with a fear of side-effects of medication, who are interested in alternative health care, might get well and replace conventional medication with this regimen.",
"title": "Vegan regimen with reduced medication in the treatment of bronchial asthma."
},
{
"docid": "MED-2491",
"text": "Exposure limits for arsenic and lead in drinking water have long been established by the U.S. Environmental Protection Agency and new regulations regarding the presence of these contaminants in bottled water went into effect in California in 2009. No comparable exposure limits or regulations are available, however, for juices and other beverages that may contain arsenic and lead. In the study described in this article, 20 apple juices (or ciders), 15 apple-containing juices, one grape, and one citrus juice were analyzed for arsenic and lead. Arsenic was detected in all juices while lead was detected in more than 94% of juices analyzed. Twelve samples (32%) demonstrated arsenic levels nearly at or above the drinking water exposure limit of 10 parts per billion. No juices contained lead above drinking water exposure limits. Expanding drinking water limits to include juices (and other frequently consumed beverages) would better protect consumers while regular testing of these juices would better inform consumers of the risks posed by specific juices and brands.",
"title": "Arsenic and lead in juice: apple, citrus, and apple-base."
},
{
"docid": "MED-1148",
"text": "PURPOSE: The etiology of hypospadias is poorly understood. Exposure to pesticides has been considered a risk factor, although findings are inconsistent. Diet constitutes a significant exposure route for pesticides, and pesticide residues are more frequently reported in conventional than organic food products. We examined the association between organic dietary choice during pregnancy and presence of hypospadias in the offspring. MATERIALS AND METHODS: Mothers of 306 boys operated on for hypospadias were frequency matched for geography and child birth year to 306 mothers of healthy boys in a case-control study. Telephone interviews were conducted regarding demographic and lifestyle factors, including intake and organic choice of selected food items (milk, dairy products, egg, fruit, vegetables and meat). Logistic regression models were constructed for dietary variables, and odds ratios were calculated controlling for maternal age, body mass index and alcohol consumption. RESULTS: Overall organic choice of food items during pregnancy was not associated with hypospadias in the offspring. However, frequent current consumption of high fat dairy products (milk, butter) while rarely or never choosing the organic alternative to these products during pregnancy was associated with increased odds of hypospadias (adjusted OR 2.18, 95% CI 1.09-4.36). CONCLUSIONS: This large case-control study of boys operated on for hypospadias suggests an association between hypospadias in the offspring and the mother not choosing the organic alternative, and having a high current intake of nonorganic butter and cheese. This finding could be due to chemical contamination of high fat dairy products. However, general lifestyle and health behavior related to choosing organic alternatives may also explain the finding. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.",
"title": "Association between organic dietary choice during pregnancy and hypospadias in offspring: a study of mothers of 306 boys operated on for hypospadias."
},
{
"docid": "MED-2656",
"text": "The aim of previous research into the causes of allergic diseases, including asthma was mostly to identify potential risk factors in the environment. No major risk factors have been identified, however. Over the past 10 years, focus has, therefore, more been directed towards protective factors that could enhance the development of tolerance to allergens which were previously encountered early in life, but are now lost in modern affluent societies. In particular, the role of childhood infections has been discussed, but so far these studies have not been conclusive. Recent epidemiological studies and experimental research suggest that the microbial environment and exposure to microbial products in infancy modifies immune responses and enhances the development of tolerance to ubiquitous allergens. The intestinal microflora may play a particular role in this respect, as it is the major external driving force in the maturation of the immune system after birth, and animal experiments have shown it to be a prerequisite for normal development of oral tolerance. Recent studies have shown differences in the composition of the microflora between healthy and allergic infants in countries with a high and low prevalence of allergies and between healthy and allergic infants within such countries. These differences are apparent within the first week of life and thus precede clinical symptoms. The use of live microorganisms that might be beneficial to health has a long tradition and the safety is well documented. Very recently, several prospective intervention studies, modifying the gut flora from birth have yielded encouraging results and may suggest a new mode of primary prevention of allergy in the future.",
"title": "Effects of intestinal microflora and the environment on the development of asthma and allergy."
},
{
"docid": "MED-1165",
"text": "The cooking-induced changes in the levels of polybrominated diphenyl ethers (PBDEs), hexachlorobenzene (HCB), and 16 polycyclic aromatic hydrocarbons (PAHs) in various foodstuffs were investigated. Foods included fish (sardine, hake and tuna), meat (veal steak, loin of pork, breast and thigh of chicken, and steak and rib of lamb), string bean, potato, rice, and olive oil. For each food item, raw and cooked (fried, grilled, roasted, boiled) samples were analyzed. There were some variations in the concentrations of PBDEs before and after cooking. However, they depended not only on the cooking process, but mainly on the specific food item. The highest HCB concentrations were found in sardine, being lower in cooked samples. All cooking processes enhanced HCB levels in hake, while very scarce differences could be noted in tuna (raw and cooked). In general terms, the highest PAH concentrations were found after frying by being the values especially notable in fish, excepting hake, where the highest total PAH levels corresponded to roasted samples. The results of this study show that, in general, cooking processes are only of a limited value as a means of reducing PBDE, HCB and PAH concentrations in food.",
"title": "Concentrations of polybrominated diphenyl ethers, hexachlorobenzene and polycyclic aromatic hydrocarbons in various foodstuffs before and after coo..."
},
{
"docid": "MED-1171",
"text": "A number of chemicals have been shown to demonstrate neurotoxic effects either in human or laboratory animal studies. This article aims at evaluating the impact of exposure to several chemicals including: organophosphate, organochlorine pesticides, polychlorinated biphenyls (PCBs), mercury and lead on the neurodevelopment of children by reviewing the most recent published literature, and answer the question whether any progress has been made in the epidemiology of the neurodevelopment of children induced by exposure to those chemicals. The result of the presented studies show that exposure to the above-mentioned chemicals may impair the neurodevelopment of children. Neonates exposed to organophosphate pesticides demonstrated a higher proportion of abnormal reflexes, and young children had more attention problems. Exposure to organochlorine pesticides in children was associated with alertness, quality of alert responsiveness, cost of attention and other potential attention associated measures. The majority of studies indicate the negative impact of lead exposure at the level <10 µg/dl or even <5 µg/dl on the neurodevelopment of children. The results of studies on exposure to PCBs, mercury, and their effect on neurodevelopment are inconsistent. Some suggest that prenatal exposure to PCBs and mercury is related to performance impairments, attention and concentration problems, while other do not present any statistically significant association. The studies were mostly well designed, using prospective cohorts with the exposure assessment based on the biomarker of exposure. Concerning the covariates and confounders affecting the endpoints in most of the presented studies, confounders were included in data analysis. In order to recognize the early cognitive, motor and language outcomes of chemical exposures, well standardized tools were used for evaluating the neurodevelopmental effects and offer an early and fairly comprehensive measure of child development. Because the neurotoxicants may cross the placenta and the fetal brain, exposure consideration regarding the reduction of exposure to those chemicals should be implemented.",
"title": "Chemical exposure early in life and the neurodevelopment of children--an overview of current epidemiological evidence."
},
{
"docid": "MED-4128",
"text": "Various methods have been described in the literature for the detection of virulent Yersinia enterocolitica in pigs. The risk factors for pig herd contamination have yet to be determined. The objective of this study was to validate a sensitive method for the detection of Y. enterocolitica and to describe the distribution of the bacteria in pigs at slaughter from conventional and alternative (\"organic\") housing systems. First, samples were collected from tonsils, caecum with caecal contents, and the caecal lymph nodes of 60 slaughter pigs. These samples were used to compare the sensitivity of six different laboratory culture methods either in common use or described in the literature with that of a polymerase chain reaction with two primer pairs (multiplex PCR). Then, only PCR was used to examine tonsils, caecum and caecal lymph nodes from two groups of slaughter pigs: 210 from six conventional fattening farms and 200 from three with alternative housing. The results of the multiplex PCR were positive in 28 cases. All culture methods proved inferior to PCR in sensitivity. In the second part of the study, PCR detected 36 (18%) positive pigs from alternative housing and 60 (29%) from conventional housing (p<0.05). The highest rate of Y. enterocolitica contamination was found in tonsils (11% alternative, 22% conventional; p<0.05), followed by caecum (5%, 11%) and lymph nodes (2%, 7%). The housing system appears to be one important factor in the prevalence of this common pathogen in pig herds, as we found important differences between the two systems studied here. In the conventional system, the main risk factors appeared to be sourcing pigs from different pig suppliers, use of commercial feed and transportation to slaughter.",
"title": "Validation of a method for the detection of virulent Yersinia enterocolitica and their distribution in slaughter pigs from conventional and alterna..."
},
{
"docid": "MED-2886",
"text": "PURPOSE: Goji berry (Lycium barbarum L.) is purported to benefit vision because of its high antioxidant (especially zeaxanthin) content, although this effect has not been demonstrated in high-quality human studies. The purpose of this study was to evaluate the effects of daily supplementation with a proprietary milk-based formulation of goji berry, Lacto-Wolfberry (LWB), on macular characteristics and plasma zeaxanthin and antioxidant capacity levels in elderly subjects. METHODS: This was a double-masked, randomized, placebo-controlled trial in healthy elderly subjects (range, 65 to 70 years) receiving 13.7 g/d of LWB (n = 75) or placebo (n = 75) for 90 days. Subjects underwent direct ophthalmic examination to assess pigmentation and soft drusen count in the macula and a blood draw to measure plasma zeaxanthin level and total antioxidant capacity. RESULTS: The placebo group demonstrated hypopigmentation and soft drusen accumulation in the macula, whereas the LWB group remained stable. Both plasma zeaxanthin level and antioxidant capacity increased significantly in the LWB group, by 26% and 57%, respectively, but did not change in the placebo group. No product-related adverse events were reported in either group. CONCLUSIONS: Overall, daily dietary supplementation with goji berry for 90 days increases plasma zeaxanthin and antioxidant levels as well as protects from hypopigmentation and soft drusen accumulation in the macula of elderly subjects. However, the mechanism of action is unclear, given the lack of relationship between change in plasma zeaxanthin and change in macular characteristics.",
"title": "Goji berry effects on macular characteristics and plasma antioxidant levels."
},
{
"docid": "MED-2482",
"text": "Previous studies have suggested that probiotic administration may have therapeutic and/or preventive effects on atopic dermatitis in infants; however, its role in allergic airway diseases remains controversial. To determine whether daily supplementation with specific Lactobacillus gasseri A5 for 8 weeks can improve the clinical symptoms and immunoregulatory changes in school children suffering from asthma and allergic rhinitis (AR). We conducted a randomized, double-blind, placebo-controlled study on school children (age, 6-12 years) with asthma and AR. The eligible study subjects received either L. gasseri A5 (n = 49) or a placebo (n = 56) daily for 2 months. Pulmonary function tests were performed, and the clinical severity of asthma and AR was evaluated by the attending physicians in the study period. Diary cards with records of the day- and nighttime peak expiratory flow rates (PEFR), symptoms of asthma, and AR scores of the patients were used for measuring the outcome of the treatment. Immunological parameters such as the total IgE and cytokine production by the peripheral blood mononuclear cells (PBMCs) were determined before and after the probiotic treatments. Our results showed the pulmonary function and PEFR increased significantly, and the clinical symptom scores for asthma and AR decreased in the probiotic-treated patients as compared to the controls. Further, there was a significant reduction in the TNF-α, IFN-γ, IL-12, and IL-13 production by the PBMCs following the probiotic treatment. In conclusion, probiotic supplementation may have clinical benefits for school children suffering from allergic airway diseases such as asthma and AR.",
"title": "Randomized placebo-controlled trial of lactobacillus on asthmatic children with allergic rhinitis."
},
{
"docid": "MED-2474",
"text": "This ISAAC Phase Three synthesis provides summarised information on the main findings of the study, regional tables and figures related to the prevalence and severity of current symptoms of asthma, rhinoconjunctivitis and eczema in the main regions of the world. The large number of surveyed children (≈1,200,000), the large number of centres (233) and countries (98) that participated in ISAAC Phase Three makes this study the most comprehensive survey of these diseases ever undertaken. Globally, the prevalence for current asthma, rhinoconjunctivitis and eczema in the 13-14-year age group was 14.1%, 14.6% and 7.3%, respectively. In the 6-7-year age group the prevalence for current asthma, rhinoconjunctivitis and eczema was 11.7%, 8.5% and 7.9%, respectively. The study shows a wide variability in the prevalence and severity of asthma, rhinoconjunctivitis and eczema which occurs not just between regions and countries but between centres in the same country and centres in the same city. This study definitively establishes that the prevalence of those diseases can be very high in non-affluent centres with low socioeconomic conditions. The large variability also suggests a crucial role of local environment characteristics to determine the differences in prevalence between one place and another. Thus, ISAAC Phase Three has provided a large body of epidemiological information on asthma, rhinoconjunctivitis and eczema in childhood from contrasting environments which is expected to yield new clues about the aetiology of those conditions and reasons for their marked global variability. Copyright © 2012 SEICAP. Published by Elsevier Espana. All rights reserved.",
"title": "The International Study of Asthma and Allergies in Childhood (ISAAC) Phase Three: a global synthesis."
},
{
"docid": "MED-2889",
"text": "Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. Cataract extraction is the most common surgical procedure in developed countries. Lutein (L) and zeaxanthin (Z), retinal carotenoids, are the most powerful retinal anti-oxidants and absorb the harmful blue light. The depletion of L+Z induces the development of the lens opacification-cataract. Cataract reduces the retinal oxidative stress (OS), which causes a reduction of the probability to develop AMD. Oxidative Stress at the retinal level is the common pathway in the development of AMD and cataract. AMD and cataract are not two independent processes. Cataract is a self-defense reaction of the retina to reduce OS and retinal damage. Restoring the anti-oxidative capabilities of the retina by increasing intake of L+Z reduces the likelihood of AMD and cataract. Extracting the opaque lens elevates the retinal OS and increases the rate of AMD. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Cataract is a self-defence reaction to protect the retina from oxidative damage."
},
{
"docid": "MED-4488",
"text": "Nitrosamines mediate their mutagenic effects by causing DNA damage, oxidative stress, lipid peroxidation, and pro-inflammatory cytokine activation, which lead to increased cellular degeneration and death. However, the very same pathophysiological processes comprise the \"unbuilding\" blocks of aging and insulin-resistance diseases including, neurodegeneration, diabetes mellitus (DM), and non-alcoholic steatohepatitis (NASH). Previous studies demonstrated that experimental exposure to streptozotocin, a nitrosamine-related compound, causes NASH, and diabetes mellitus Types 1, 2 and 3 (Alzheimer (AD)-type neurodegeneration). Herein, we review evidence that the upwardly spiraling trends in mortality rates due to DM, AD, and Parkinson's disease typify exposure rather than genetic-based disease models, and parallel the progressive increases in human exposure to nitrates, nitrites, and nitrosamines via processed/preserved foods. We propose that such chronic exposures have critical roles in the pathogenesis of our insulin resistance disease pandemic. Potential solutions include: 1) eliminating the use of nitrites in food; 2) reducing nitrate levels in fertilizer and water used to irrigate crops; and 3) employing safe and effective measures to detoxify food and water prior to human consumption. Future research efforts should focus on refining our ability to detect and monitor human exposures to nitrosamines and assess early evidence of nitrosamine-mediated tissue injury and insulin resistance.",
"title": "Epidemilogical trends strongly suggest exposures as etiologic agents in the pathogenesis of sporadic Alzheimer's disease, diabetes mellitus, and no..."
},
{
"docid": "MED-2885",
"text": "OBJECTIVE: This overview of ultraviolet (UV) phototoxicity considers the interaction of UVA and short-wavelength VIS light with the retina and retinal pigment epithelium. METHODS: The damage mechanisms underlying UV retinal phototoxicity are illustrated with a literature survey and presentation of experimental results. RESULTS: Depending on the wavelength and exposure duration, light interacts with tissue by three general mechanisms: thermal, mechanical, or photochemical. Although the anterior structures of the eye absorb much of the UV component of the optical radiation spectrum, a portion of the UVA band (315-400 nm) penetrates into the retina. Natural sources, such as the sun, emit energetic UV photons in relatively long durations, which typically do not result in energy confinement in the retina, and thus do not produce thermal or mechanical damage but are capable of inducing photochemical damage. Photochemical damage in the retina proceeds through Type 1 (direct reactions involving proton or electron transfers) and Type 2 (reactions involving reactive oxygen species) mechanisms. Commonly used drugs, such as certain antibiotics, nonsteroidal anti-inflammatory drugs, psychotherapeutic agents, and even herbal medicines, may act as photosensitizers that promote retinal UV damage, if they are excited by UVA or visible light and have sufficient retinal penetration. CONCLUSIONS: Although the anterior portion of the eye is the most susceptible to UV damage, the retina is at risk to the longer UV wavelengths that propagate through the ocular media. Some phototoxicity may be counteracted or reduced by dietary intake of antioxidants and protective phytonutrients.",
"title": "Ultraviolet phototoxicity to the retina."
},
{
"docid": "MED-2659",
"text": "U.S. and European regulators and researchers disagree over risks of a common class of surfactants.",
"title": "European bans on surfactant trigger transatlantic debate."
},
{
"docid": "MED-2749",
"text": "Noroviruses are the leading cause of foodborne illness in the United States. To better guide interventions, we analyzed 2,922 foodborne disease outbreaks for which norovirus was the suspected or confirmed cause, which had been reported to the Foodborne Disease Outbreak Surveillance System of the Centers for Disease Control and Prevention during 2001–2008. On average, 365 foodborne norovirus outbreaks were reported annually, resulting in an estimated 10,324 illnesses, 1,247 health care provider visits, 156 hospitalizations, and 1 death. In 364 outbreaks attributed to a single commodity, leafy vegetables (33%), fruits/nuts (16%), and mollusks (13%) were implicated most commonly. Infected food handlers were the source of 53% of outbreaks and may have contributed to 82% of outbreaks. Most foods were likely contaminated during preparation and service, except for mollusks, and occasionally, produce was contaminated during production and processing. Interventions to reduce the frequency of foodborne norovirus outbreaks should focus on food workers and production of produce and shellfish.",
"title": "Epidemiology of Foodborne Norovirus Outbreaks, United States, 2001–2008"
},
{
"docid": "MED-4136",
"text": "BACKGROUND: In the United States, contaminated food causes approximately 1,000 reported disease outbreaks and an estimated 48 million illnesses, 128,000 METHODS: The Foodborne Diseases Active Surveillance Network (FoodNet) conducts surveillance among 15% of the U.S. population for laboratory-confirmed infections with nine pathogens transmitted commonly through food. Overall and pathogen-specific changes in incidence were estimated from 1996-1998 to 2010 and from 2006-2008 to 2010.hospitalizations, and 3,000 deaths annually. This report summarizes 2010 surveillance data and describes trends since 1996. RESULTS: A total of 19,089 infections, 4,247 hospitalizations, and 68 deaths were reported from FoodNet sites in 2010. Salmonella infection was the most common infection reported (17.6 illnesses per 100,000 persons) and was associated with the largest number of hospitalizations (2,290) and deaths (29); no significant change in incidence of Salmonella infection has occurred since the start of surveillance during 1996-1998. Shiga toxin-producing Escherichia coli (STEC) O157 infection caused 0.9 illnesses per 100,000. Compared with 1996-1998, overall incidence of infection with six key pathogens in 2010 was 23% lower, and pathogen-specific incidence was lower for Campylobacter, Listeria, STEC O157, Shigella, and Yersinia infection but higher for Vibrio infection. Compared with a more recent period, 2006--2008, incidence in 2010 was lower for STEC O157 and Shigella infection but higher for Vibrio infection. CONCLUSIONS: The incidence of STEC O157 infection has declined to reach the 2010 national health objective target of ≥1 case per 100,000. This success, as well as marked declines since 1996-1998 in overall incidence of six key foodborne infections, demonstrates the feasibility of preventing foodborne illnesses. IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Salmonella infection should be targeted because it has not declined significantly in more than a decade, and other data indicate that it is one of the most common foodborne infections, resulting in an estimated $365 million in direct medical costs annually. The prevention measures that reduced STEC O157 infection need to be applied more broadly to reduce Salmonella and other infections. Effective measures from farm to table include preventing contamination of meat during slaughter and of all foods, including produce, during processing and preparation; cooking meat thoroughly; vigorously detecting and investigating outbreaks; and recalling contaminated food.",
"title": "Vital signs: incidence and trends of infection with pathogens transmitted commonly through food--foodborne diseases active surveillance network, 10..."
},
{
"docid": "MED-1172",
"text": "Background The widespread use of organophosphorus (OP) pesticides has led to frequent exposure in adults and children. Because such exposure may cause adverse health effects, particularly in children, the sources and patterns of exposure need to be studied further. Objectives We assessed young urban/suburban children’s longitudinal exposure to OP pesticides in the Children’s Pesticide Exposure Study (CPES) conducted in the greater Seattle, Washington, area, and used a novel study design that allowed us to determine the contribution of dietary intake to the overall OP pesticide exposure. Methods Twenty-three children 3–11 years of age who consumed only conventional diets were recruited for this 1-year study conducted in 2003–2004. Children switched to organic diets for 5 consecutive days in the summer and fall sampling seasons. We measured specific urinary metabolites for malathion, chlorpyrifos, and other OP pesticides in urine samples collected twice daily for a period of 7, 12, or 15 consecutive days during each of the four seasons. Results By substituting organic fresh fruits and vegetables for corresponding conventional food items, the median urinary metabolite concentrations were reduced to nondetected or close to non-detected levels for malathion and chlorpyrifos at the end of the 5-day organic diet intervention period in both summer and fall seasons. We also observed a seasonal effect on the OP urinary metabolite concentrations, and this seasonality corresponds to the consumption of fresh produce throughout the year. Conclusions The findings from this study demonstrate that dietary intake of OP pesticides represents the major source of exposure in young children.",
"title": "Dietary Intake and Its Contribution to Longitudinal Organophosphorus Pesticide Exposure in Urban/Suburban Children"
},
{
"docid": "MED-2476",
"text": "An increase in asthma and atopic disease has been recorded in many countries where society has become more prosperous. We have investigated two possible explanations: a reduction in childhood infections and a change in diet. In a cohort of people followed up since 1964, originally selected as a random sample of primary school children, we have investigated the relevance of family size and the common childhood infectious diseases to development of eczema, hay fever and asthma. Although membership of a large family reduced risks of hay fever and eczema (but not asthma), this was not explained by the infections the child had suffered. Indeed, the more infections the child had had, the greater the likelihood of asthma, although measles gave a modest measure of protection. We have investigated dietary factors in two separate studies. In the first, we have shown the risks of bronchial hyper-reactivity are increased seven-fold among those with the lowest intake of vitamin C, while the lowest intake of saturated fats gave a 10-fold protection. In the second, we have shown that the risk of adult-onset wheezy illness is increased five-fold by the lowest intake of vitamin E and doubled by the lowest intake of vitamin C. These results were supported by direct measurements of the vitamins and triglycerides in plasma. We have proposed that changes in the diet of pregnant women may have reflected those observed in the population as a whole and that these may have resulted in the birth of cohorts of children predisposed to atopy and asthma. The direct test of this is to study the diet and nutritional status of a large cohort of pregnant women and to follow their offspring forward. This is our current research.",
"title": "Diet, infection and wheezy illness: lessons from adults."
},
{
"docid": "MED-5168",
"text": "OBJECTIVE: To investigate the possible role of the maternal diet, particularly vegetarianism and consumption of phytoestrogens, in the origin of hypospadias, which is reported to be increasing in prevalence. SUBJECTS AND METHODS: Detailed information was obtained prospectively from mothers, including previous obstetric history, lifestyle and dietary practices, using structured self-completed questionnaires during pregnancy. Previously recognized associations with environmental and parental factors were examined, focusing particularly on the hypothesized hormonal link. Multivariate logistic regression was used to identify independent associations. RESULTS: Of 7928 boys born to mothers taking part in the Avon Longitudinal Study of Pregnancy and Childhood, 51 hypospadias cases were identified. There were no significant differences in the proportion of hypospadias cases among mothers who smoked, consumed alcohol or for any aspect of their previous reproductive history (including the number of previous pregnancies, number of miscarriages, use of the contraceptive pill, time to conception and age at menarche). Significant differences were detected for some aspects of the maternal diet, i.e. vegetarianism and iron supplementation in the first half of pregnancy. Mothers who were vegetarian in pregnancy had an adjusted odds ratio (OR) of 4.99 (95% confidence interval, CI, 2.10-11.88) of giving birth to a boy with hypospadias, compared with omnivores who did not supplement their diet with iron. Omnivores who supplemented their diet with iron had an adjusted OR of 2.07 (95% CI, 1.00-4.32). The only other statistically significant association for hypospadias was with influenza in the first 3 months of pregnancy (adjusted OR 3.19, 95% CI 1.50-6.78). CONCLUSION: As vegetarians have a greater exposure to phytoestrogens than do omnivores, these results support the possibility that phytoestrogens have a deleterious effect on the developing male reproductive system.",
"title": "A maternal vegetarian diet in pregnancy is associated with hypospadias. The ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood."
},
{
"docid": "MED-2772",
"text": "Prostate cancer has become the most common cancer among men in the United States. Although milk consumption is considered to be a risk factor in some epidemiological studies, the results are inconsistent. A meta-analysis method was conducted to estimate the combined odds ratio (OR) between milk consumption and prostate cancer from case-control studies published between 1984 and 2003 using commercial software (comprehensive meta-analysis). The combined OR was 1.68 (95% confidence interval = 1.34-2.12) in the 11 published case-control studies. The combined OR varied little by study stratification. Additionally, we evaluated the possible risk factors in milk for prostate cancer. In conclusion, we found a positive association between milk consumption and prostate cancer. The underlying mechanisms, including fat, calcium, hormones, and other factors, should be investigated further. Copyright 2004 Lawrence Erlbaum Associates, Inc.",
"title": "Milk consumption is a risk factor for prostate cancer: meta-analysis of case-control studies."
},
{
"docid": "MED-1157",
"text": "In 1997 this laboratory initiated a research program with the objective of examining the effect that rinsing of produce with tap water would have on pesticide residues. Samples were obtained from local markets and/or grown at our experimental farm. Because approximately 35% of produce from retail sources contains pesticide residues, growing and treating produce at an experimental farm had the advantage that all such samples contain pesticide residues. Pesticides were applied under normal field conditions to a variety of food crops and the vegetation was allowed to undergo natural weathering prior to harvest. The resulting samples contained field-incurred or \"field-fortified\" residues. This experimental design was employed to mimic as closely as possible real world samples. Crops were treated, harvested, and divided into equal subsamples. One subsample was processed unwashed, whereas the other was rinsed under tap water. The extraction and analysis method used was a multi-residue method developed in our laboratory. Twelve pesticides were included in this study: the fungicides captan, chlorothalonil, iprodione, and vinclozolin; and the insecticides endosulfan, permethrin, methoxychlor, malathion, diazinon, chlorpyrifos, bifenthrin, and DDE (a soil metabolite of DDT). Statistical analysis of the data using the Wilcoxon signed-rank test showed that rinsing removed residues for nine of the twelve pesticides studied. Residues of vinclozolin, bifenthrin, and chlorpyrifos were not reduced. The rinsability of a pesticide is not correlated with its water solubility.",
"title": "Reduction of pesticide residues on produce by rinsing."
},
{
"docid": "MED-2475",
"text": "Current understanding of the use of exclusion diets in the management of asthma in children is limited and controversial. The aim of this study was to examine the effects of excluding eggs and milk on the occurrence of symptoms in children with asthma and involved 22 children aged between three and 14 years clinically diagnosed as having mild to moderate disease. The investigation was single blind and prospective, and parents were given the option of volunteering to join the 'experiment' group, avoiding eggs, milk and their products for eight weeks, or the 'control' group, who consumed their customary food. Thirteen children were recruited to the experimental group and nine to the control group. A trained paediatrician at the beginning and end of the study period assessed the children. A seven-day assessment of food intake was made before, during and immediately after the period of dietary intervention in both groups. A blood sample was taken from each child for determination of food specific antibodies and in those children who could do so, the peak expiratory flow rate (PEFR) was measured. Based on the recommended nutrient intake (RNI), the mean percentage energy intake of the children in the experimental group was significantly lower (p < 0.05) in the experimental group. After the eight-week study period and compared with baseline values, the mean serum anti-ovalbumin IgG and anti-beta lactoglobulin IgG concentrations were statistically significantly reduced (p < 0.05) for both in the experimental group. In contrast, the values for anti-ovalbumin IgG in the control group were significantly increased and those for anti-beta lactoglobulin IgG were practically unchanged. The total IgE values were unchanged in both groups. Over the study period, the PEFR in those children in the experimental group able to perform the test was significantly increased, but no such change was noted in the children in the control group who could do the test. These results suggest that even over the short time period of eight weeks, an egg- and milk-free diet can reduce atopic symptoms and improve lung function in asthmatic children.",
"title": "The effects of exclusion of dietary egg and milk in the management of asthmatic children: a pilot study."
},
{
"docid": "MED-1164",
"text": "We assessed organophosphorus (OP) pesticide exposure from diet by biological monitoring among Seattle, Washington, preschool children. Parents kept food diaries for 3 days before urine collection, and they distinguished organic and conventional foods based on label information. Children were then classified as having consumed either organic or conventional diets based on analysis of the diary data. Residential pesticide use was also recorded for each home. We collected 24-hr urine samples from 18 children with organic diets and 21 children with conventional diets and analyzed them for five OP pesticide metabolites. We found significantly higher median concentrations of total dimethyl alkylphosphate metabolites than total diethyl alkylphosphate metabolites (0.06 and 0.02 micro mol/L, respectively; p = 0.0001). The median total dimethyl metabolite concentration was approximately six times higher for children with conventional diets than for children with organic diets (0.17 and 0.03 micro mol/L; p = 0.0003); mean concentrations differed by a factor of nine (0.34 and 0.04 micro mol/L). We calculated dose estimates from urinary dimethyl metabolites and from agricultural pesticide use data, assuming that all exposure came from a single pesticide. The dose estimates suggest that consumption of organic fruits, vegetables, and juice can reduce children's exposure levels from above to below the U.S. Environmental Protection Agency's current guidelines, thereby shifting exposures from a range of uncertain risk to a range of negligible risk. Consumption of organic produce appears to provide a relatively simple way for parents to reduce their children's exposure to OP pesticides.",
"title": "Organophosphorus pesticide exposure of urban and suburban preschool children with organic and conventional diets."
},
{
"docid": "MED-2494",
"text": "Background In the absence of current cumulative dietary exposure assessments, this analysis was conducted to estimate exposure to multiple dietary contaminants for children, who are more vulnerable to toxic exposure than adults. Methods We estimated exposure to multiple food contaminants based on dietary data from preschool-age children (2–4 years, n=207), school-age children (5–7 years, n=157), parents of young children (n=446), and older adults (n=149). We compared exposure estimates for eleven toxic compounds (acrylamide, arsenic, lead, mercury, chlorpyrifos, permethrin, endosulfan, dieldrin, chlordane, DDE, and dioxin) based on self-reported food frequency data by age group. To determine if cancer and non-cancer benchmark levels were exceeded, chemical levels in food were derived from publicly available databases including the Total Diet Study. Results Cancer benchmark levels were exceeded by all children (100%) for arsenic, dieldrin, DDE, and dioxins. Non-cancer benchmarks were exceeded by >95% of preschool-age children for acrylamide and by 10% of preschool-age children for mercury. Preschool-age children had significantly higher estimated intakes of 6 of 11 compounds compared to school-age children (p<0.0001 to p=0.02). Based on self-reported dietary data, the greatest exposure to pesticides from foods included in this analysis were tomatoes, peaches, apples, peppers, grapes, lettuce, broccoli, strawberries, spinach, dairy, pears, green beans, and celery. Conclusions Dietary strategies to reduce exposure to toxic compounds for which cancer and non-cancer benchmarks are exceeded by children vary by compound. These strategies include consuming organically produced dairy and selected fruits and vegetables to reduce pesticide intake, consuming less animal foods (meat, dairy, and fish) to reduce intake of persistent organic pollutants and metals, and consuming lower quantities of chips, cereal, crackers, and other processed carbohydrate foods to reduce acrylamide intake.",
"title": "Cancer and non-cancer health effects from food contaminant exposures for children and adults in California: a risk assessment"
},
{
"docid": "MED-1152",
"text": "The incidence of testicular cancer (TC) has been increasing worldwide during the last decades. The reasons of the increase remains unknown, but recent findings suggest that organochlorine pesticides (OPs) could influence the development of TC. A hospital-based case-control study of 50 cases and 48 controls was conducted to determine whether environmental exposure to OPs is associated with the risk of TC, and by measuring serum concentrations of OPs, including p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) isomer and hexachlorobenzene (HCB) in participants. A significant association was observed between TC and household insecticide use (odds ratio [OR] = 3.01, 95 % CI: 1.11-8.14; OR(adjusted) = 3.23, 95 % CI: 1.15-9.11). Crude and adjusted ORs for TC were also significantly associated with higher serum concentrations of total OPs (OR = 3.15, 95 % CI: 1.00-9.91; OR(adjusted) = 3.34, 95 % CI: 1.09-10.17) in cases compared with controls. These findings give additional support to the results of previous research that suggest that some environmental exposures to OPs may be implicated in the pathogenesis of TC.",
"title": "Pesticide exposure and serum organochlorine residuals among testicular cancer patients and healthy controls."
},
{
"docid": "MED-1732",
"text": "Glyphosate is an active ingredient of the most widely used herbicide and it is believed to be less toxic than other pesticides. However, several recent studies showed its potential adverse health effects to humans as it may be an endocrine disruptor. This study focuses on the effects of pure glyphosate on estrogen receptors (ERs) mediated transcriptional activity and their expressions. Glyphosate exerted proliferative effects only in human hormone-dependent breast cancer, T47D cells, but not in hormone-independent breast cancer, MDA-MB231 cells, at 10⁻¹² to 10⁻⁶M in estrogen withdrawal condition. The proliferative concentrations of glyphosate that induced the activation of estrogen response element (ERE) transcription activity were 5-13 fold of control in T47D-KBluc cells and this activation was inhibited by an estrogen antagonist, ICI 182780, indicating that the estrogenic activity of glyphosate was mediated via ERs. Furthermore, glyphosate also altered both ERα and β expression. These results indicated that low and environmentally relevant concentrations of glyphosate possessed estrogenic activity. Glyphosate-based herbicides are widely used for soybean cultivation, and our results also found that there was an additive estrogenic effect between glyphosate and genistein, a phytoestrogen in soybeans. However, these additive effects of glyphosate contamination in soybeans need further animal study. Copyright © 2013 Elsevier Ltd. All rights reserved.",
"title": "Glyphosate induces human breast cancer cells growth via estrogen receptors."
},
{
"docid": "MED-1728",
"text": "The United States Environmental Protection Agency and other regulatory agencies around the world have registered glyphosate as a broad-spectrum herbicide for use on multiple food and non-food use crops. Glyphosate is widely considered by regulatory authorities and scientific bodies to have no carcinogenic potential, based primarily on results of carcinogenicity studies of rats and mice. To examine potential cancer risks in humans, we reviewed the epidemiologic literature to evaluate whether exposure to glyphosate is associated causally with cancer risk in humans. We also reviewed relevant methodological and biomonitoring studies of glyphosate. Seven cohort studies and fourteen case-control studies examined the association between glyphosate and one or more cancer outcomes. Our review found no consistent pattern of positive associations indicating a causal relationship between total cancer (in adults or children) or any site-specific cancer and exposure to glyphosate. Data from biomonitoring studies underscore the importance of exposure assessment in epidemiologic studies, and indicate that studies should incorporate not only duration and frequency of pesticide use, but also type of pesticide formulation. Because generic exposure assessments likely lead to exposure misclassification, it is recommended that exposure algorithms be validated with biomonitoring data. Copyright © 2012 Elsevier Inc. All rights reserved.",
"title": "Epidemiologic studies of glyphosate and cancer: a review."
},
{
"docid": "MED-1150",
"text": "The “organic food” market is the fastest growing food sector, yet it is unclear whether organically raised food is nutritionally superior to conventionally grown food and whether consuming organic food bestows health benefits. In order to evaluate potential health benefits of organic foods, we used the well-characterized fruit fly Drosophila melanogaster as a model system. Fruit flies were raised on a diets consisting of extracts of either conventionally or organically raised produce (bananas, potatoes, raisins, soy beans). Flies were then subjected to a variety of tests designed to assess overall fly health. Flies raised on diets made from organically grown produce had greater fertility and longevity. On certain food sources, greater activity and greater stress resistance was additionally observed, suggesting that organic food bestows positive effects on fly health. Our data show that Drosophila can be used as a convenient model system to experimentally test potential health effects of dietary components. Using this system, we provide evidence that organically raised food may provide animals with tangible benefits to overall health.",
"title": "Organically Grown Food Provides Health Benefits to Drosophila melanogaster"
},
{
"docid": "MED-2747",
"text": "Each year, >9 million foodborne illnesses are estimated to be caused by major pathogens acquired in the United States. Preventing these illnesses is challenging because resources are limited and linking individual illnesses to a particular food is rarely possible except during an outbreak. We developed a method of attributing illnesses to food commodities that uses data from outbreaks associated with both simple and complex foods. Using data from outbreak-associated illnesses for 1998–2008, we estimated annual US foodborne illnesses, hospitalizations, and deaths attributable to each of 17 food commodities. We attributed 46% of illnesses to produce and found that more deaths were attributed to poultry than to any other commodity. To the extent that these estimates reflect the commodities causing all foodborne illness, they indicate that efforts are particularly needed to prevent contamination of produce and poultry. Methods to incorporate data from other sources are needed to improve attribution estimates for some commodities and agents.",
"title": "Attribution of Foodborne Illnesses, Hospitalizations, and Deaths to Food Commodities by using Outbreak Data, United States, 1998–2008"
},
{
"docid": "MED-1737",
"text": "Roundup is the major herbicide used worldwide, in particular on genetically modified plants that have been designed to tolerate it. We have tested the toxicity and endocrine disruption potential of Roundup (Bioforce on human embryonic 293 and placental-derived JEG3 cells, but also on normal human placenta and equine testis. The cell lines have proven to be suitable to estimate hormonal activity and toxicity of pollutants. The median lethal dose (LD(50)) of Roundup with embryonic cells is 0.3% within 1 h in serum-free medium, and it decreases to reach 0.06% (containing among other compounds 1.27 mM glyphosate) after 72 h in the presence of serum. In these conditions, the embryonic cells appear to be 2-4 times more sensitive than the placental ones. In all instances, Roundup (generally used in agriculture at 1-2%, i.e., with 21-42 mM glyphosate) is more efficient than its active ingredient, glyphosate, suggesting a synergistic effect provoked by the adjuvants present in Roundup. We demonstrated that serum-free cultures, even on a short-term basis (1 h), reveal the xenobiotic impacts that are visible 1-2 days later in serum. We also document at lower non-overtly toxic doses, from 0.01% (with 210 microM glyphosate) in 24 h, that Roundup is an aromatase disruptor. The direct inhibition is temperature-dependent and is confirmed in different tissues and species (cell lines from placenta or embryonic kidney, equine testicular, or human fresh placental extracts). Furthermore, glyphosate acts directly as a partial inactivator on microsomal aromatase, independently of its acidity, and in a dose-dependent manner. The cytotoxic, and potentially endocrine-disrupting effects of Roundup are thus amplified with time. Taken together, these data suggest that Roundup exposure may affect human reproduction and fetal development in case of contamination. Chemical mixtures in formulations appear to be underestimated regarding their toxic or hormonal impact.",
"title": "Time- and dose-dependent effects of roundup on human embryonic and placental cells."
},
{
"docid": "MED-2773",
"text": "In Japan dramatic lifestyle changes occurred after World War 2. To examine the experience of Japan as a clue to the etiology, trends in the mortality rates of testicular and prostatic cancers from 1947 to 1998 were related to changes in dietary practices. The male population born before 1945 had a peak in death from testicular cancer in their thirties or forties, whereas those born after 1946 had a peak in their twenties. The death rate of prostatic cancer increased 25-fold almost linearly after the war. The intake of milk, meat, and eggs increased 20-, 9-, and 7-fold, respectively, after the war. In connection with the development and growth of testicular and prostatic cancers in Japan, particular attention should be paid to milk, because the increase in its consumption in this country is a recent occurrence and because milk contains considerable amounts of estrogens plus saturated fats.",
"title": "The experience of Japan as a clue to the etiology of testicular and prostatic cancers."
},
{
"docid": "MED-2898",
"text": "PURPOSE: Age and advanced disease in the fellow eye are the two most important risk factors for age-related macular degeneration (AMD). In this study, the authors investigated the relationship between these variables and the optical density of macular pigment (MP) in a group of subjects from a northern European population. METHODS: The optical density of MP was measured psychophysically in 46 subjects ranging in age from 21 to 81 years with healthy maculae and in 9 healthy eyes known to be at high-risk of AMD because of advanced disease in the fellow eye. Each eye in the latter group was matched with a control eye on the basis of variables believed to be associated with the optical density of MP (iris color, gender, smoking habits, age, and lens density). RESULTS: There was an age-related decline in the optical density of macular pigment among volunteers with no ocular disease (right eye: r(2) = 0.29, P = 0.0006; left eye: r(2) = 0.29, P < 0.0001). Healthy eyes predisposed to AMD had significantly less MP than healthy eyes at no such risk (Wilcoxon's signed rank test: P = 0.015). CONCLUSIONS: The two most important risk factors for AMD are associated with a relative absence of MP. These findings are consistent with the hypothesis that supplemental lutein and zeaxanthin may delay, avert, or modify the course of this disease.",
"title": "Macular pigment and risk for age-related macular degeneration in subjects from a Northern European population."
},
{
"docid": "MED-4129",
"text": "Pigs are considered as a major reservoir of human pathogenic Yersinia enterocolitica and a source of human yersiniosis. However, the transmission route of Y. enterocolitica from farm to pork is still unclear. The transmission of pathogenic Y. enterocolitica from pigs to carcasses and pluck sets was investigated by collecting samples from 364 individual ear-tagged pigs on the farm and at the slaughterhouse. In addition, isolated strains were analyzed, using pulsed-field gel electrophoresis. Isolation of similar genotypes of pathogenic Y. enterocolitica 4/O:3 in animals on the farm and at the slaughterhouse and in carcasses shows that carcass contamination originates from the strains a pig carries during the fattening period. Direct contamination from the carrier pig to its subsequent pluck set is also the primary contamination route for pluck sets, but cross-contamination appears to have a larger impact on pluck set contamination than on carcasses. In this study, the within-farm prevalence of pathogenic Y. enterocolitica varied from 0% to 100%, indicating specific farm factors affect the prevalence of Y. enterocolitica in pigs. The association of farm factors with the high prevalence of pathogenic Y. enterocolitica on farms was studied for the first time, using correlation and two-level logistic regression analyses. Specific farm factors, i.e. drinking from a nipple, absence of coarse feed or bedding for slaughter pigs, and no access of pest animals to pig house, were associated with a high prevalence of pathogenic Y. enterocolitica 4/O:3.",
"title": "Contamination of carcasses with human pathogenic Yersinia enterocolitica 4/O:3 originates from pigs infected on farms."
},
{
"docid": "MED-4143",
"text": "In this study, we hoped to provide valuable clinical information on yersiniosis for clinicians. Two thousand six hundred stool samples were collected from in- and outpatients with diarrhea, which were tested with both culture method and real-time polymerase chain reaction (RT-PCR). In total, 188 positive samples were detected by RT-PCR (178) and culture method (160), while the incidence was about 7.23%. The detection rate of RT-PCR was significantly higher than culture method and a higher incidence in autumn-winter was also noticeably identified than in spring-summer. Infection sources mostly focused on unboiled foods (101) and pets (45), while clinical manifestation mainly presented as gastroenteritis (156), pseudoappendicitis (32), and extraintestinal complications (46). The morbidity of extraintestinal complications in adults was significantly higher than in children and it was the same for high-risk patients between adults over the age of 60 years (4.7%) and children under the age of 3 years (1.4%), whereas the constituent ratio of children versus adults with yersiniosis in different systems was not significant. Of 160 isolates tested for antimicrobial susceptibility, the majority were susceptible to third-generation cephalosporins, aminoglycosides, fluoroquinolones, and trimethoprim-sulfamethoxazole, whereas only a small portion was susceptible to the first-generation cephalosporins and penicillins. During autumn-winter months, clinicians should pay more attention to clinical manifestation, early diagnosis, and treatment with susceptible antibiotics of yersiniosis and its complications, targeting high-risk patients.",
"title": "Yersinia enterocolitica infection in diarrheal patients."
},
{
"docid": "MED-2893",
"text": "Lutein and zeaxanthin are thought to decrease the incidence of age-related macular degeneration (AMD); however, findings have been inconsistent. We conducted a systematic literature review and meta-analysis to evaluate the relationship between dietary intake of lutein and zeaxanthin and AMD risk. Relevant studies were identified by searching five databases up to April 2010. Reference lists of articles were retrieved, and experts were contacted. Literature search, data extraction and study quality assessment were performed independently by two reviewers and results were pooled quantitatively using meta-analysis methods. The potential sources of heterogeneity and publication bias were also estimated. The search yielded six longitudinal cohort studies. The pooled relative risk (RR) for early AMD, comparing the highest with the lowest category of lutein and zeaxanthin intake, was 0·96 (95 % CI 0·78, 1·17). Dietary intake of these carotenoids was significantly related with a reduction in risk of late AMD (RR 0·74; 95 % CI 0·57, 0·97); and a statistically significant inverse association was observed between lutein and zeaxanthin intake and neovascular AMD risk (RR 0·68; 95 % CI 0·51, 0·92). The results were essentially consistent among subgroups stratified by participant characteristics. The findings of the present meta-analysis indicate that dietary lutein and zeaxanthin is not significantly associated with a reduced risk of early AMD, whereas an increase in the intake of these carotenoids may be protective against late AMD. However, additional studies are needed to confirm these relationships.",
"title": "Lutein and zeaxanthin intake and the risk of age-related macular degeneration: a systematic review and meta-analysis."
},
{
"docid": "MED-3882",
"text": "Salmonella enterica is one of the most common causes of foodborne illness in the United States. Although salmonellosis is usually self-limiting, severe infections typically require antimicrobial treatment, and ceftriaxone, an extended-spectrum cephalosporin (ESC), is commonly used in both adults and children. Surveillance conducted by the National Antimicrobial Resistance Monitoring System (NARMS) has shown a recent increase in ESC resistance among Salmonella Heidelberg isolated from food animals at slaughter, retail meat, and humans. ESC resistance among Salmonella in the United States is usually mediated by a plasmid-encoded bla(CMY) β-lactamase. In 2009, we identified 47 ESC-resistant bla(CMY)-positive Heidelberg isolates from humans (n=18), food animals at slaughter (n=16), and retail meats (n=13) associated with a spike in the prevalence of this serovar. Almost 90% (26/29) of the animal and meat isolates were isolated from chicken carcasses or retail chicken meat. We screened NARMS isolates for the presence of bla(CMY), determined whether the gene was plasmid-encoded, examined pulsed-field gel electrophoresis patterns to assess the genetic diversities of the isolates, and categorized the bla(CMY) plasmids by plasmid incompatibility groups and plasmid multi-locus sequence typing (pMLST). All 47 bla(CMY) genes were found to be plasmid encoded. Incompatibility/replicon typing demonstrated that 41 were IncI1 plasmids, 40 of which only conferred bla(CMY)-associated resistance. Six were IncA/C plasmids that carried additional resistance genes. pMLST of the IncI1-bla(CMY) plasmids showed that 27 (65.8%) were sequence type (ST) 12, the most common ST among bla(CMY)-IncI1 plasmids from Heidelberg isolated from humans. Ten plasmids had a new ST profile, ST66, a type very similar to ST12. This work showed that the 2009 increase in ESC resistance among Salmonella Heidelberg was caused mainly by the dissemination of bla(CMY) on IncI1 and IncA/C plasmids in a variety of genetic backgrounds, and is likely not the result of clonal expansion.",
"title": "Characterization of extended-spectrum cephalosporin-resistant Salmonella enterica serovar Heidelberg isolated from food animals, retail meat, and h..."
},
{
"docid": "MED-3891",
"text": "Escherichia coli isolates were recovered from the National Antimicrobial Resistance Monitoring System retail meat program and examined for antimicrobial susceptibility. Retail meat samples (n = 11,921) from four U.S. states collected during 2002 to 2008, consisting of 2,988 chicken breast, 2,942 ground turkey, 2,991 ground beef, and 3,000 pork chop samples, were analyzed. A total of 8,286 E. coli isolates were recovered. The greatest numbers of samples contaminated with the organism were chicken (83.5%) and turkey (82.0%), followed by beef (68.9%) and pork (44.0%). Resistance was most common to tetracycline (50.3%), followed by streptomycin (34.6%), sulfamethoxazole-sulfisoxazole (31.6%), ampicillin (22.5%), gentamicin (18.6%), kanamycin (8.4%), amoxicillin-clavulanic acid (6.4%), and cefoxitin (5.2%). Less than 5% of the isolates had resistance to trimethoprim, ceftriaxone, ceftiofur, nalidixic acid, chloramphenicol, and ciprofloxacin. All isolates were susceptible to amikacin. Compared to beef and pork isolates, the poultry meat isolates had a greater percentage of resistance to all tested drugs, with the exception of chloramphenicol, to which pork isolates had the most resistance. More than half of the turkey isolates (56%) were resistant to multidrugs (≥3 classes) compared to 38.9% of chicken, 17.3% of pork, and 9.3% of beef isolates. The blaCMY gene was present in all ceftriaxone- and ceftiofur-resistant isolates. The cmlA, flo, and catI genes were present in 45%, 43%, and 40% of chloramphenicol-resistant isolates, respectively. Most nalidixic acid-resistant isolates (98.5%) had a gyrA mutation in S83 or D87 or both, whereas only 6.7% had a parC mutation in either S80 or E84. The results showed that E. coli was commonly present in the retail meats, and antimicrobial resistance profiles differed according to the animal origin of the isolates.",
"title": "Comparison of the Prevalences and Antimicrobial Resistances of Escherichia coli Isolates from Different Retail Meats in the United States, 2002 to 2008"
},
{
"docid": "MED-5167",
"text": "OBJECTIVES: The phytoestrogen (plant estrogen) genistein, present in soy products, is of interest because in utero exposure to genistein can cause hypospadias in our mouse model and maternal consumption of soy is prevalent in human populations. Another compound of interest is the fungicide vinclozolin, which also causes hypospadias in the mouse and rat and can occur concurrently with genistein in the diet as a residue on exposed foods. A study in the United Kingdom found no relationship between a maternal organic vegetarian diet and hypospadias frequency, but women who consumed nonorganic vegetarian diets had a greater percentage of sons with hypospadias. Because nonorganic diets can include residues of pesticides such as vinclozolin, we sought to assess the interaction of realistic daily exposures to genistein and vinclozolin and their effects on the incidence of hypospadias. METHODS: Pregnant mice were fed a soy-free diet and orally gavaged from gestational days 13 to 17 with 0.17 mg/kg/day of genistein, 10 mg/kg/day of vinclozolin, or genistein and vinclozolin together at the same doses, all in 100 microL of corn oil. The controls received the corn oil vehicle. The male fetuses were examined at gestational day 19 for hypospadias, both macroscopically and histologically. RESULTS: We identified no hypospadias in the corn oil group. The incidence of hypospadias was 25% with genistein alone, 42% with vinclozolin alone, and 41% with genistein and vinclozolin together. CONCLUSIONS: These findings support the idea that exposure to these compounds during gestation could contribute to the development of hypospadias.",
"title": "Endocrine disruptors and hypospadias: role of genistein and the fungicide vinclozolin."
},
{
"docid": "MED-2471",
"text": "The International Study of Asthma and Allergies in Childhood (ISAAC) Phase One showed large worldwide variations in the prevalence of symptoms of asthma, rhinoconjunctivitis and eczema, up to 10 to 20 fold between countries. Ecological analyses were undertaken with ISAAC Phase One data to explore factors that may have contributed to these variations, and are summarised and reviewed here. In ISAAC Phase One the prevalence of symptoms in the past 12 months of asthma, rhinoconjunctivitis and eczema were estimated from studies in 463,801 children aged 13 - 14 years in 155 centres in 56 countries, and in 257,800 children aged 6-7 years in 91 centres in 38 countries. Ecological analyses were undertaken between symptom prevalence and the following: Gross National Product per capita (GNP), food intake, immunisation rates, tuberculosis notifications, climatic factors, tobacco consumption, pollen, antibiotic sales, paracetamol sales, and outdoor air pollution. Symptom prevalence of all three conditions was positively associated with GNP, trans fatty acids, paracetamol, and women smoking, and inversely associated with food of plant origin, pollen, immunisations, tuberculosis notifications, air pollution, and men smoking. The magnitude of these associations was small, but consistent in direction between conditions. There were mixed associations of climate and antibiotic sales with symptom prevalence. The potential causality of these associations warrant further investigation. Factors which prevent the development of these conditions, or where there is an absence of a positive correlation at a population level may be as important from the policy viewpoint as a focus on the positive risk factors. Interventions based on small associations may have the potential for a large public health benefit.",
"title": "Which population level environmental factors are associated with asthma, rhinoconjunctivitis and eczema? Review of the ecological analyses of ISAAC Phase One"
},
{
"docid": "MED-2484",
"text": "Paediatric asthma is a major clinical concern worldwide and represents a huge burden on family and society. It accounts for a large number of lost school days and may deprive the child of both academic achievement and social interaction. Childhood asthma also places strain on healthcare resources as a result of doctor and hospital visits and the cost of treatment. The prevalence of asthma varies worldwide, possibly because of different exposure to respiratory infection, indoor and outdoor pollution, and diet. Certain risk factors appear to predispose children to developing asthma and atopic disease, including incidence and severity of wheezing, atopy, maternal smoking, and number of fever episodes. This paper discusses the burden, prevalence, and risk factors associated with paediatric asthma.",
"title": "The burden of childhood asthma"
},
{
"docid": "MED-5070",
"text": "Polyphenol-rich berry extracts were screened for their antiproliferative effectiveness using human cervical cancer (HeLa) cells grown in microtiter plates. Rowan berry, raspberry, lingonberry, cloudberry, arctic bramble, and strawberry extracts were effective but blueberry, sea buckthorn, and pomegranate extracts were considerably less effective. The most effective extracts (strawberry > arctic bramble > cloudberry > lingonberry) gave EC 50 values in the range of 25-40 microg/(mL of phenols). These extracts were also effective against human colon cancer (CaCo-2) cells, which were generally more sensitive at low concentrations but conversely less sensitive at higher concentrations. The strawberry, cloudberry, arctic bramble, and the raspberry extracts share common polyphenol constituents, especially the ellagitannins, which have been shown to be effective antiproliferative agents. However, the components underlying the effectiveness of the lingonberry extracts are not known. The lingonberry extracts were fractionated into anthocyanin-rich and tannin-rich fractions by chromatography on Sephadex LH-20. The anthocyanin-rich fraction was considerably less effective than the original extract, whereas the antiproliferative activity was retained in the tannin-rich fraction. The polyphenolic composition of the lingonberry extract was assessed by liquid chromatography-mass spectrometry and was similar to previous reports. The tannin-rich fraction was almost entirely composed of procyanidins of linkage type A and B. Therefore, the antiproliferative activity of lingonberry was caused predominantly by procyanidins.",
"title": "Berry extracts exert different antiproliferative effects against cervical and colon cancer cells grown in vitro."
},
{
"docid": "MED-2645",
"text": "The development of the male reproductive ducts and external genitalia in vertebrates is dependent on elevated androgen concentrations during embryonic development and the period of postnatal growth. We have observed that a population of juvenile alligators living on Lake Apopka exhibit significantly smaller penis size (24% average decrease) and lower plasma concentrations of testosterone (70% lower concentrations) when compared to animals of similar size on Lake Woodruff. In addition to smaller phalli, no relationship exists between plasma testosterone concentrations and penile size in males from Lake Apopka, whereas a positive relationship exists for males from Lake Woodruff. The alligators on Lake Apopka are known to have elevated concentrations of the antiandrogenic DDT breakdown product p.p'-DDE stored in their fat. We suggest a number of hypotheses that could explain the modification in the phenotype of the juvenile male living in Lake Apopka. These modifications in phenotype include a smaller penis size, lower plasma androgen concentrations, and lack of responsiveness of the penis to the plasma androgens present.",
"title": "Reduction in penis size and plasma testosterone concentrations in juvenile alligators living in a contaminated environment."
},
{
"docid": "MED-2892",
"text": "PURPOSE: The purpose of this study was to investigate the effect of bilberry on night visual acuity (VA) and night contrast sensitivity (CS). METHODS: This study utilized a double-blind, placebo-controlled, crossover design. The subjects were young males with good vision; eight received placebo and seven received active capsules for three weeks. Active capsules contained 160 mg of bilberry extract (25-percent anthocyanosides), and the placebo capsules contained only inactive ingredients. Subjects ingested one active or placebo capsule three times daily for 21 days. After the three-week treatment period, a one-month washout period was employed to allow any effect of bilberry on night vision to dissipate. In the second three-week treatment period, the eight subjects who first received placebo were given active capsules, and the seven who first received active capsules were given placebo. Night VA and night CS was tested throughout the three-month experiment. RESULTS: There was no difference in night VA during any of the measurement periods when examining the average night VA or the last night VA measurement during active and placebo treatments. In addition, there was no difference in night CS during any of the measurement periods when examining the average night CS or the last night CS measurement during active and placebo treatments. CONCLUSION: The current study failed to find an effect of bilberry on night VA or night CS for a high dose of bilberry taken for a significant duration. Hence, the current study casts doubt on the proposition that bilberry supplementation, in the forms currently available and in the doses recommended, is an effective treatment for the improvement of night vision in this population.",
"title": "The effect of bilberry nutritional supplementation on night visual acuity and contrast sensitivity."
},
{
"docid": "MED-1587",
"text": "OBJECTIVE: To evaluate the possible biochemical effect of diet and heredity on the rates of monozygotic and dizygotic twinning. STUDY DESIGN: In that insulin-like growth factor (IGF) has been found to be elevated in cows selected for their demonstrated increased twinning rate, the effect of agents that influence the level of IGF in women was examined. This was correlated with their prior history of singleton versus twin birthing. In particular, the effect of diets consisting of or excluding animal products that have elevated IGF content (e.g., milk) was considered. RESULTS: Vegan women, who exclude dairy products from their diets, have a twinning rate which is one-fifth that of vegetarians and omnivores. CONCLUSION: The results reported here support the proposed IGF model of dizygotic twinning. Genotypes favoring elevated IGF and diets including dairy products, especially in areas where growth hormone is given to cattle, appear to enhance the chances of multiple pregnancies due to ovarian stimulation.",
"title": "Mechanisms of twinning: VII. Effect of diet and heredity on the human twinning rate."
},
{
"docid": "MED-1738",
"text": "Glyphosate is the active ingredient of several widely used herbicide formulations. Glyphosate targets the shikimate metabolic pathway, which is found in plants but not in animals. Despite the relative safety of glyphosate, various adverse developmental and reproductive problems have been alleged as a result of exposure in humans and animals. To assess the developmental and reproductive safety of glyphosate, an analysis of the available literature was conducted. Epidemiological and animal reports, as well as studies on mechanisms of action related to possible developmental and reproductive effects of glyphosate, were reviewed. An evaluation of this database found no consistent effects of glyphosate exposure on reproductive health or the developing offspring. Furthermore, no plausible mechanisms of action for such effects were elucidated. Although toxicity was observed in studies that used glyphosate-based formulations, the data strongly suggest that such effects were due to surfactants present in the formulations and not the direct result of glyphosate exposure. To estimate potential human exposure concentrations to glyphosate as a result of working directly with the herbicide, available biomonitoring data were examined. These data demonstrated extremely low human exposures as a result of normal application practices. Furthermore, the estimated exposure concentrations in humans are >500-fold less than the oral reference dose for glyphosate of 2 mg/kg/d set by the U.S. Environmental Protection Agency (U.S. EPA 1993). In conclusion, the available literature shows no solid evidence linking glyphosate exposure to adverse developmental or reproductive effects at environmentally realistic exposure concentrations.",
"title": "Developmental and reproductive outcomes in humans and animals after glyphosate exposure: a critical analysis."
}
] |
[
{
"docid": "MED-3628",
"text": "The distribution and behaviour of the natural-series alpha-emitter polonium-210 in the marine environment has been under study for many years primarily due to its enhanced bioaccumulation, its strong affinity for binding with certain internal tissues, and its importance as a contributor to the natural radiation dose received by marine biota as well as humans consuming seafoods. Results from studies spanning nearly 5 decades show that (210)Po concentrations in organisms vary widely among the different phylogenic groups as well as between the different tissues of a given species. Such variation results in (210)Po concentration factors ranging from approximately 10(3) to over 10(6) depending upon the organism or tissue considered. (210)Po/(210)Pb ratios in marine species are generally greater than unity and tend to increase up the food chain indicating that (210)Po is preferentially taken up by organisms compared to its progenitor (210)Pb. The effective transfer of (210)Po up the food chain is primarily due to the high degree of assimilation of the radionuclide from ingested food and its subsequent strong retention in the organisms. In some cases this mechanism may lead to an apparent biomagnification of (210)Po at the higher trophic level. Various pelagic species release (210)Po and (210)Pb packaged in organic biodetrital particles that sink and remove these radionuclides from the upper water column, a biogeochemical process which, coupled with scavenging rates of this radionuclide pair, is being examined as a possible proxy for estimating downward organic carbon fluxes in the sea. Data related to preferential bioaccumulation in various organisms, their tissues, resultant radiation doses to these species, and the processes by which (210)Po is transferred and recycled through the food web are discussed. In addition, the main gaps in our present knowledge and proposed areas for future studies on the biogeochemical behaviour of (210)Po and its use as a tracer of oceanographic processes are highlighted in this review. Copyright © 2010 Elsevier Ltd. All rights reserved.",
"title": "210Po in the marine environment with emphasis on its behaviour within the biosphere."
},
{
"docid": "MED-4604",
"text": "We determined the genotoxicity of 39 chemicals currently in use as food additives. They fell into six categories-dyes, color fixatives and preservatives, preservatives, antioxidants, fungicides, and sweeteners. We tested groups of four male ddY mice once orally with each additive at up to 0.5xLD(50) or the limit dose (2000mg/kg) and performed the comet assay on the glandular stomach, colon, liver, kidney, urinary bladder, lung, brain, and bone marrow 3 and 24h after treatment. Of all the additives, dyes were the most genotoxic. Amaranth, Allura Red, New Coccine, Tartrazine, Erythrosine, Phloxine, and Rose Bengal induced dose-related DNA damage in the glandular stomach, colon, and/or urinary bladder. All seven dyes induced DNA damage in the gastrointestinal organs at a low dose (10 or 100mg/kg). Among them, Amaranth, Allura Red, New Coccine, and Tartrazine induced DNA damage in the colon at close to the acceptable daily intakes (ADIs). Two antioxidants (butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT)), three fungicides (biphenyl, sodium o-phenylphenol, and thiabendazole), and four sweeteners (sodium cyclamate, saccharin, sodium saccharin, and sucralose) also induced DNA damage in gastrointestinal organs. Based on these results, we believe that more extensive assessment of food additives in current use is warranted.",
"title": "The comet assay with 8 mouse organs: results with 39 currently used food additives."
},
{
"docid": "MED-2407",
"text": "Background Persistent organic pollutants (POPs) are hazardous chemicals omnipresent in our food chain, which have been internationally regulated to ensure public health. Initially described for their potency to affect reproduction and promote cancer, recent studies have highlighted an unexpected implication of POPs in the development of metabolic diseases like type 2 diabetes and obesity. Based on this novel knowledge, this article aims at stimulating discussion and evaluating the effectiveness of current POP legislation to protect humans against the risk of metabolic diseases. Furthermore, the regulation of POPs in animal food products in the European Union (EU) is addressed, with a special focus on marine food since it may represent a major source of POP exposure to humans. Discussion There is mounting scientific evidence showing that current POP risk assessment and regulation cannot effectively protect humans against metabolic disorders. Better regulatory control of POPs in dietary products should be of high public health priority. Summary The general population is exposed to sufficient POPs, both in term of concentration and diversity, to induce metabolic disorders. This situation should attract the greatest attention from the public health and governmental authorities.",
"title": "Public health concern behind the exposure to persistent organic pollutants and the risk of metabolic diseases"
},
{
"docid": "MED-3385",
"text": "Diacetyl-containing butter flavor was identified as the cause of an outbreak of bronchiolitis obliterans (BO) and other lung diseases in popcorn-plant workers. Litigation documents show that the outbreak was both predictable and preventable. The industry trade organization was aware of BO cases in workers at butter-flavoring and popcorn-manufacturing plants but often failed to implement industrial hygiene improvements and actively hid pertinent warning information. Due to weaknesses in the organization and mandates of regulatory bodies, organizations such as NIOSH, OSHA, the FDA, particularly the \"generally recognized as safe\" (GRAS) system, and the EPA failed to detect and prevent the outbreak, which highlights the need for systemic changes in food-product regulation, including the need for corporations to act responsibly, for stronger regulations with active enforcement, for a restructuring of the GRAS system, and for criminal penalties against corporations and professionals who knowingly hide information relevant to worker protection.",
"title": "Popcorn-worker lung caused by corporate and regulatory negligence: an avoidable tragedy."
},
{
"docid": "MED-1793",
"text": "Most research studies in the field of dietary polyphenols or phenolic compounds use a chemical approach focusing exclusively on polyphenols extracted from plant foods with organic solvents. However, an appreciable part of polyphenols are not extracted with organic solvents and thus are ignored in biological, nutritional, and epidemiological studies. Recent studies have shown that these nonextractable polyphenols (NEPP) are a major part of total dietary polyphenols and that they exhibit a significant biological activity. A physiological approach is proposed on the basis that the bioavailability and health-related properties of polyphenols depend on their solubility in intestinal fluids, which is different from their solubility in organic solvents. This paper tries to clarify the concept of NEPP, distinguishing between chemical and physiological approaches and pointing out the main qualitative and quantitative differences between them. It is stressed that the literature and databases refer to only extractable polyphenols. Greater attention to NEPP may fill the current gap in the field of dietary polyphenols.",
"title": "Concept and health-related properties of nonextractable polyphenols: the missing dietary polyphenols."
},
{
"docid": "MED-1441",
"text": "Most ethnic foods and cooking practices have incorporated the use of spices and other food additives. Many common spices have crossed cultural boundaries and appear in multiple ethnic cuisines. Recent studies have demonstrated that many of these ingredients possess antimicrobial properties against common food spoilage microorganisms. We developed a laboratory exercise that promotes the use of scientific methodology to evaluate the effectiveness of salsa components at inhibiting the growth of undesirable microorganisms. Tomato, onion, garlic, cilantro, and jalapeño were tested for antimicrobial properties against a representative fungus, Saccharomyces cerevisiae, and the common food spoilage bacteria Staphylococcus aureus, Bacillus cereus, and Escherichia coli. Each component was ethanol extracted and a modification of the Kirby-Bauer method of antimicrobial sensitivity was employed. Garlic demonstrated the greatest inhibitory effects against all organisms tested. Onion demonstrated a slight inhibition of all four organisms, while cilantro showed some inhibition of all three bacteria but no effect against the fungus. Jalapeño may have slightly inhibited E. coli and S. aureus, as evidenced by a consistently measured increase in the zone of inhibition that was not statistically significant when compared to that of the control. Following the initial exercise, students were given the opportunity to repeat the exercise using other spices such as cinnamon, clove, nutmeg, and coriander. Student learning outcomes were evaluated using preliminary and secondary surveys, mainly focusing on definitions of science and hypothesis as well as the process of science. Students enjoyed this exercise and met the learning goals of understanding the process and methodology of science, as well as the interdisciplinarity inherent in the sciences. Student learning was evidenced by an increase in the number of correct responses on the secondary survey in comparison to the preliminary.",
"title": "The Science of Salsa: Antimicrobial Properties of Salsa Components to Learn Scientific Methodology"
},
{
"docid": "MED-5077",
"text": "Due to the increased demand and consumption of bottled water in the United States, there has been a growing concern about the quality of this product. Retail outlets sell local as well as imported bottled water to consumers. Three bottles for each of 35 different brands of bottled water were randomly collected from local grocery stores in the greater Houston area. Out of the 35 different brands, 16 were designated as spring water, 11 were purified and/or fortified tap water, 5 were carbonated water and 3 were distilled water. Chemical, microbial and physical properties of all samples were evaluated including pH, conductivity, bacteria counts, anion concentration, trace metal concentration, heavy metal and volatile organics concentration were determined in all samples. Inductively coupled plasma/mass spectrometry (ICPMS) was used for elemental analysis, gas chromatography with electron capture detector (GCECD) as well as gas chromatography mass spectrometry (GCMS) were used for analysis of volatile organics, ion chromatography (IC) and selective ion electrodes were used for the analysis of anions. Bacterial identification was performed using the Biolog software (Biolog, Inc., Hayward, Ca, USA). The results obtained were compared with guidelines of drinking water recommended by the International Bottled Water Association (IBWA), United States Food and Drug Administration (FDA), United States Environmental Protection Agency (EPA) and the World Health Organization (WHO) drinking water standard. The majority of the analyzed chemicals were below their respective drinking water standards for maximum admissible concentrations (MAC). Volatile organic chemicals were found to be below detection limits. Four of the 35 brands of the bottled water samples analyzed were found to be contaminated with bacteria.",
"title": "Chemical, microbial and physical evaluation of commercial bottled waters in greater Houston area of Texas."
},
{
"docid": "MED-4727",
"text": "The objective of this study was to estimate the intake of organic tin compounds from foodstuffs in a Finnish market basket. The study was conducted by collecting 13 market baskets from supermarkets and market places in the city of Kuopio, eastern Finland. Altogether 115 different food items were bought. In each basket, foodstuffs were mixed in proportion to their consumption and analysed by GC/MS for seven organic tin compounds (mono-, di-, and tributyltin, mono-, di-, and triphenyltin, and dioctyltin). Organotin compounds were detected in only four baskets, with the fish basket containing the largest number of different organotins. The European Food Safety Authority has established a tolerable daily intake of 250 ng kg(-1) body weight for the sum of dibutyltin, tributyltin, triphenyltin and dioctyltin. According to this study, the daily intake of these compounds was 2.47 ng kg(-1) body weight, of which 81% originated from the fish basket. This exposure is only 1% of the tolerable daily intake and poses negligible risk to the average consumer. However, for consumers eating large quantities of fish from contaminated areas, the intake may be much higher.",
"title": "Dietary intake of organotin compounds in Finland: a market-basket study."
},
{
"docid": "MED-2088",
"text": "Organoarsenical drugs are widely used in the production of broiler chickens in the United States. Feathers from these chickens are processed into a meal product that is used as an animal feed additive and as an organic fertilizer. Research conducted to date suggests that arsenical drugs, specifically roxarsone, used in poultry production result in the accumulation of arsenic in the keratinous material of poultry feathers. The use of feather meal product in the human food system and in other settings may result in human exposures to arsenic. Consequently, the presence and nature of arsenic in twelve samples of feather meal product from six US states and China were examined. Since arsenic toxicity is highly species-dependent, speciation analysis using HPLC/ICPMS was performed to determine the biological relevance of detected arsenic. Arsenic was detected in all samples (44-4100 μg kg(-1)) and speciation analyses revealed that inorganic forms of arsenic dominated, representing 37 - 83% of total arsenic. Roxarsone was not detected in the samples (<20 μg As kg(-1)). Feather meal products represent a previously unrecognized source of arsenic in the food system, and may pose additional risks to humans as a result of its use as an organic fertilizer and when animal waste is managed. Copyright © 2011 Elsevier B.V. All rights reserved.",
"title": "Arsenic species in poultry feather meal."
},
{
"docid": "MED-1055",
"text": "OBJECTIVE: To indicate why the world's most powerful nation state and one powerful sector of the food and drink production and manufacturing industry are determined to demolish the 2004 WHO (World Health Organization) global strategy on diet, physical activity and health, and to disassociate it from the 2003 WHO/FAO (Food and Agriculture Organization) expert report on diet, nutrition and the prevention of chronic diseases, which with its background papers is the immediate scientific basis for the strategy. To encourage representatives of nation states at the 2004 WHO World Health Assembly to support the strategy together with the report, so that the strategy is explicit and quantified, and responds to the need expressed by member states at the 2002 World Health Assembly. This is for an effective global strategy to prevent and control chronic diseases whose prevalence is increased by nutrient-poor food low in vegetables and fruits and high in energy-dense fatty, sugary and/or salty foods and drinks and also by physical inactivity. Of these diseases, obesity, diabetes, cardiovascular diseases and cancers of several sites are now the chief causes of morbidity and mortality in most countries in the world. METHOD: A summary of the global strategy and its roots in scientific knowledge accumulated over the last half-century. Reasons why the global strategy and the expert report are opposed by the current US government and the world sugar industry, with some reference to modern historical context. A summary of the trajectory of the global strategy since its first draft made in early 2003, and a further summary of its weaknesses, strengths and potential. CONCLUSION: The 2004 WHO global strategy and the 2003 WHO/FAO expert report are perceived by the current US administration as an impediment to US trade and international policy, within a general context of current US government hostility to the UN (United Nations) system as a brake on the exercise of its power as the world's dominant nation. Policy-makers throughout the world should be aware of the contexts of current pressures put on them by powerful nation states and sectors of industry whose ideologies and commercial interests are challenged by international initiatives designed to improve public health and to leave a better legacy for future generations.",
"title": "Why the Bush administration and the global sugar industry are determined to demolish the 2004 WHO global strategy on diet, physical activity and he..."
},
{
"docid": "MED-1058",
"text": "The Sugar Association, representing the U.S. sugar industry, is highly critical of a WHO report on guidelines for healthy eating, which suggests that sugar should account for no more than 10 percent of a healthy diet. The association has demanded that Congress end its funding of the World Health Organization unless the WHO withdraws the guidelines, and the association and six other big food industry groups have also asked the U.S. Secretary of Health and Human Services to use his influence to get the WHO report withdrawn. The WHO strongly rejects the sugar lobby's criticisms.",
"title": "Political context of the World Health Organization: sugar industry threatens to scupper the WHO."
},
{
"docid": "MED-3221",
"text": "Background The finding reported in a previous paper - alkalization of urine facilitates uric acid excretion - is contradictory to what one might expect to occur: because food materials for the alkalization of urine contain fewer purine bodies than those for acidification, less uric acid in alkaline urine should have been excreted than in acid urine. To make clear what component of uric acid excretion mechanisms is responsible for this unexpected finding, we simultaneously collected data for the concentration of both creatinine and uric acid in serum as well as in urine, in order to calculate both uric acid and creatinine clearances. Methods Within the framework of the Japanese government’s health promotion program, we made recipes which consisted of protein-rich and less vegetable-fruit food materials for H + -load (acidic diet) and others composed of less protein and more vegetable-fruit rich food materials (alkaline diet). This is a crossover study within some limitations. Healthy female students, who had no medical problems at the regular physical examination provided by the university, were enrolled in this consecutive 5-day study for each test. From whole-day collected urine, total volume, pH, organic acid, creatinine, uric acid, titratable acid and all cations (Na+,K+,Ca2+,Mg2+,NH4+) and anions (Cl−,SO42−,PO4−) necessary for the estimation of acid–base balance were measured. In the early morning before breakfast of the 1st, 3rd and 5th experimental day, we sampled 5 mL of blood to estimate the creatinine and uric acid concentration in serum. Results and discussion Urine pH reached a steady state 3 days after switching from ordinary daily diets to specified regimens. The amount of acid generated ([SO42−] + organic acid − gut alkali)was linearly related with the excretion of acid (titratable acid + [NH4+] − [HCO3−]), indicating that H + in urine is generated by the metabolic degradation of food materials. Uric acid and excreted urine pH retained a linear relationship, as reported previously. Among the five factors which are associated with calculating clearances for both uric acid and creatinine, we identified a conspicuous difference between acidic and alkaline diets in the uric acid concentration in serum as well as in urine; uric acid in the serum was higher in the acidic group than in the alkaline group, while uric acid in the urine in the acidic group was lower than that in the alkaline group. These changes of uric acid in acidic urine and in serum were reflected in the reduction of its clearance. From these observations, it is considered that uric acid may be reabsorbed more actively in acidic urine than in alkaline urine. Conclusion We conclude that alkalization of urine by eating nutritionally well-designed alkaline -prone food is effective for removing uric acid from the body.",
"title": "Effect of urine pH changed by dietary intervention on uric acid clearance mechanism of pH-dependent excretion of urinary uric acid"
},
{
"docid": "MED-3649",
"text": "Most human extraintestinal Escherichia coli infections, including those involving antimicrobial resistant strains, are caused by the members of a limited number of distinctive E. coli lineages, termed extraintestinal pathogenic E. coli (ExPEC), that have a special ability to cause disease at extraintestinal sites when they exit their usual reservoir in the host's intestinal tract. Multiple lines of evidence suggest that many of the ExPEC strains encountered in humans with urinary tract infection, sepsis, and other extraintestinal infections, especially the most extensively antimicrobial-resistant strains, may have a food animal source, and may be transmitted to humans via the food supply. This review summarizes the evidence that food-borne organisms are a significant cause of extraintestinal E. coli infections in humans.",
"title": "Food-borne origins of Escherichia coli causing extraintestinal infections."
},
{
"docid": "MED-1601",
"text": "Natural and organic food regulations preclude the use of sodium nitrite/nitrate and other antimicrobials for processed meat products. Consequently, processors have begun to use natural nitrate/nitrite sources, such as celery juice/powder, sea salt, and turbinado sugar, to manufacture natural and organic products with cured meat characteristics but without sodium nitrite. The objective of this study was to compare physio-chemical characteristics that affect Clostridium perfringens and Listeria monocytogenes growth in naturally cured and traditionally cured commercial frankfurters, hams, and bacon. Correlations of specific product characteristics to pathogen growth varied between products and pathogens, though water activity, salt concentration, and product composition (moisture, protein and fat) were common intrinsic factors correlated to pathogen growth across products. Other frequently correlated traits were related to curing reactions such as % cured pigment. Residual nitrite and nitrate were significantly correlated to C. perfringens growth but only for the ham products. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Survey of naturally and conventionally cured commercial frankfurters, ham, and bacon for physio-chemical characteristics that affect bacterial growth."
},
{
"docid": "MED-4205",
"text": "Since the Second World War the consumer behaviour in developed countries changed drastically. Primarily there existed the demand for sufficient food after a period of starvation, afterwards the desire for higher quality was arising, whereas today most people ask for safe and healthy food with high quality. Therefore a united approach comprising consistent standards, sound science and robust controls is required to ensure consumers' health and to maintain consumers' confidence and satisfaction. Chemical analysis along the whole food chain downstream (tracking) from primary production to the consumer and upstream (tracing) from the consumer to primary production is an important prerequisite to ensure food safety and quality. In this frame the focus of the following paper is the \"chemical safety of meat and meat products\" taking into account inorganic as well as organic residues and contaminants, the use of nitrite in meat products, the incidence of veterinary drugs, as well as a Failure Mode and Effect Analysis (FMEA) system assessing (prioritizing) vulnerable food chain steps to decrease or eliminate vulnerability.",
"title": "Chemical safety of meat and meat products."
},
{
"docid": "MED-3522",
"text": "Melatonin has been detected in bacteria, eukaryotic unicells, macroalgae, plants, fungi and various taxa of invertebrates. Although precise determinations are missing in many of these organisms and the roles of melatonin are still unknown, investigations in some species allow more detailed conclusions. Non-vertebrate melatonin is not necessarily circadian, and if so, not always peaking at night, although nocturnal maxima are frequently found. In the cases under study, the major biosynthetic pathway is identical with that of vertebrates. Mimicking of photoperiodic responses and concentration changes upon temperature decreases have been studied in more detail only in dinoflagellates. In plants, an involvement in photoperiodism seems conceivable but requires further support. No stimulation of flowering has been demonstrated to date. A participation in antioxidative protection might be possible in many aerobic non-vertebrates, although evidence for a contribution at physiological levels is mostly missing. Protection from stress by oxidotoxins or/and extensions of lifespan have been shown in very different organisms, such as the dinoflagellate Lingulodinium, the ciliate Paramecium, the rotifer Philodina and Drosophila. Melatonin can be taken up from the food, findings with possible implications in ecophysiology as well as for human nutrition and, with regard to high levels in medicinal plants, also in pharmacology.",
"title": "Non-vertebrate melatonin."
},
{
"docid": "MED-1217",
"text": "Clostridium difficile has been recognized as an important human pathogen for several decades, but its importance as an agent of animal disease was established only recently. The number of reports on C. difficile in food is rising, but the findings vary among studies. In North America, the prevalence of contamination in retail meat and meat products ranges from 4.6% to 50%. In European countries, the percentage of C. difficile positive samples is much lower (0-3%). This chapter summarizes current data on association of C. difficile with different foods and the difficulties associated with isolation of the organism, and discusses the potential of C. difficile as a food-transmitted pathogen. Copyright © 2010 Elsevier Inc. All rights reserved.",
"title": "Clostridium difficile: its potential as a source of foodborne disease."
},
{
"docid": "MED-4635",
"text": "The increased flow of goods, people, and ideas associated with globalization have contributed to an increase in noncommunicable diseases in much of the world. One response has been to encourage lifestyle changes with educational programmes, thus controlling the lifestyle-related disease. Key assumptions with this approach are that people's food preferences are linked to their consumption patterns, and that consumption patterns can be transformed through educational initiatives. To investigate these assumptions, and policies that derive from it, we undertook a broad-based survey of food-related issues in the Kingdom of Tonga using a questionnaire. Data on the relationships between food preferences, perception of nutritional value, and frequency of consumption were gathered for both traditional and imported foods. The results show that the consumption of health-compromising imported foods was unrelated either to food preferences or to perceptions of nutritional value, and suggests that diet-related diseases may not be amenable to interventions based on education campaigns. Given recent initiatives towards trade liberalization and the creation of the World Trade Organization, tariffs or import bans may not serve as alternative measures to control consumption. This presents significant challenges to health policy-makers serving economically marginal populations and suggests that some population health concerns cannot be adequately addressed without awareness of the effects of global trade.",
"title": "Globalization, diet, and health: an example from Tonga."
},
{
"docid": "MED-3090",
"text": "Background Hyperphosphatemia has been identified in the past decade as a strong predictor of mortality in advanced chronic kidney disease (CKD). For example, a study of patients in stage CKD 5 (with an annual mortality of about 20%) revealed that 12% of all deaths in this group were attributable to an elevated serum phosphate concentration. Recently, a high-normal serum phosphate concentration has also been found to be an independent predictor of cardiovascular events and mortality in the general population. Therefore, phosphate additives in food are a matter of concern, and their potential impact on health may well have been underappreciated. Methods We reviewed pertinent literature retrieved by a selective search of the PubMed and EU databases (www.zusatzstoffe-online.de, www.codexalimentarius.de), with the search terms “phosphate additives” and “hyperphosphatemia.” Results There is no need to lower the content of natural phosphate, i.e. organic esters, in food, because this type of phosphate is incompletely absorbed; restricting its intake might even lead to protein malnutrition. On the other hand, inorganic phosphate in food additives is effectively absorbed and can measurably elevate the serum phosphate concentration in patients with advanced CKD. Foods with added phosphate tend to be eaten by persons at the lower end of the socioeconomic scale, who consume more processed and “fast” food. The main pathophysiological effect of phosphate is vascular damage, e.g. endothelial dysfunction and vascular calcification. Aside from the quality of phosphate in the diet (which also requires attention), the quantity of phosphate consumed by patients with advanced renal failure should not exceed 1000 mg per day, according to the guidelines. Conclusion Prospective controlled trials are currently unavailable. In view of the high prevalence of CKD and the potential harm caused by phosphate additives to food, the public should be informed that added phosphate is damaging to health. Furthermore, calls for labeling the content of added phosphate in food are appropriate.",
"title": "Phosphate Additives in Food—a Health Risk"
},
{
"docid": "MED-1237",
"text": "It has become widely accepted that Type 2 diabetes is inevitably life-long, with irreversible and progressive beta cell damage. However, the restoration of normal glucose metabolism within days after bariatric surgery in the majority of people with Type 2 diabetes disproves this concept. There is now no doubt that this reversal of diabetes depends upon the sudden and profound decrease in food intake, and does not relate to any direct surgical effect. The Counterpoint study demonstrated that normal glucose levels and normal beta cell function could be restored by a very low calorie diet alone. Novel magnetic resonance methods were applied to measure intra-organ fat. The results showed two different time courses: a) resolution of hepatic insulin sensitivity within days along with a rapid fall in liver fat and normalisation of fasting glucose levels; and b) return of normal beta cell insulin secretion over weeks in step with a fall in pancreas fat. Now that it has been possible to observe the pathophysiological events during reversal of Type 2 diabetes, the reverse time course of events which determine the onset of the condition can be identified. The twin cycle hypothesis postulates that chronic calorie excess leads to accumulation of liver fat with eventual spill over into the pancreas. These self-reinforcing cycles between liver and pancreas eventually cause metabolic inhibition of insulin secretion after meals and onset of hyperglycaemia. It is now clear that Type 2 diabetes is a reversible condition of intra-organ fat excess to which some people are more susceptible than others.",
"title": "Banting Memorial Lecture 2012 Reversing the twin cycles of Type 2 diabetes"
},
{
"docid": "MED-2650",
"text": "Over the last 40 years there have been constant reports concerning environmental chemicals with hormone-like effects in wildlife. An endocrine disruptor is an exogenous substance that causes adverse health effects in an intact organism or its progeny, secondary to changes in endocrine function. Endocrine disruptors of widely diverse chemical structures that have oestrogenic properties are known as oestrogenic xenobiotics or xenoestrogens. Some of these substances, such as phytoestrogens and mycoestrogens, can come from diet or from the environment. Although the oestrogenic activity of these substances is weaker than that of oestradiol, new chemicals with endocrine disrupting potential continue to be discovered, inadvertent forms of exposure are constantly being identified, and there is increasing concern about cumulative effects. Studies in the 1960s and 1970s characterized the oestrogenicity of a number of industrial compounds and the pesticides o,p-DDT, kepone, methoxychlor, phenolic derivatives and polychlorinated biphenyls (PCBs). In the last 5 years, several environmental chemicals have been added to the list of xenoestrogens, including the pesticides toxaphene, dieldrin and endosulphan, and several different compounds used in the food industry, antioxidants such a t-butylhydroxyanisole; plasticizers such as benzylbutylphthalate and 4-OH-alkylphenols; and substances used in dental restorations, such as bisphenol-A. The relevance of these newly discovered endocrine disruptors to human health is now starting to emerge. The few studies that have investigated their effect in humans point in the same direction: if there is indeed an association between exposure to substances with hormone-disruptive activity and certain disorders of endocrine organs, the incidence of such disorders would be greater in areas where exposure to agents with this activity is high. A closer scrutiny is required to determine whether these newly discovered endocrine disrupting chemicals contribute, together with oestrogenic pesticides, to the exposure of humans to xenoestrogens.",
"title": "Inadvertent exposure to xenoestrogens."
},
{
"docid": "MED-4442",
"text": "For many years, it was believed that the main function of the large intestine was the resorption of water and salt and the facilitated disposal of waste materials. However, this task definition was far from complete, as it did not consider the activity of the microbial content of the large intestine. Nowadays it is clear that the complex microbial ecosystem in our intestines should be considered as a separate organ within the body, with a metabolic capacity which exceeds the liver with a factor 100. The intestinal microbiome is therefore closely involved in the first-pass metabolism of dietary compounds. This is especially true for botanical supplements, which are now marketed for various health applications. Being of natural origin, their structural building blocks, such as polyphenols, are often highly recognized by the human and especially the intestinal microbial metabolism machinery. Intensive metabolism results in often low circulating levels of the original products, with the consequence that final health effects of botanicals are often related to specific active metabolites which are produced in the body rather than being related to the product's original composition. Understanding how such metabolic processes contribute to the in situ exposure is therefore crucial for the proper interpretation of biological responses. A multidisciplinary approach, characterizing the food and phytochemical intake as well as the metabolic potency of the gut microbiota, while measuring biomarkers of both exposure and response in target tissues, is therefore of critical importance. With polyphenol metabolism as example, this review describes how the incorporation of microbial metabolism as an important variable in the evaluation of the final bioactivity of botanicals strongly increases the relevance and predictive value of the outcome. Moreover, knowledge about intestinal processes may offer innovative strategies for targeted product development. Copyright © 2010 Elsevier B.V. All rights reserved.",
"title": "The intestinal microbiome: a separate organ inside the body with the metabolic potential to influence the bioactivity of botanicals."
},
{
"docid": "MED-2391",
"text": "Objectives The objective of this article is to extend our previous studies of persistent organic pollutant (POP) contamination of U.S. food by measuring perfluorinated compounds (PFCs), organochlorine pesticides, and polychlorinated biphenyls (PCBs) in composite food samples. This study is part of a larger study reported in two articles, the other of which reports levels of polybrominated diphenyl ethers and hexabromocyclododecane brominated flame retardants in these composite foods [Schecter et al. 2010. Polybrominated diphenyl ethers (PBDEs) and hexabromocyclodecane (HBCD) in composite U.S. food samples, Environ Health Perspect 118:357–362]. Methods In this study we measured concentrations of 32 organochlorine pesticides, 7 PCBs, and 11 PFCs in composite samples of 31 different types of food (310 individual food samples) purchased from supermarkets in Dallas, Texas (USA), in 2009. Dietary intake of these chemicals was calculated for an average American. Results Contamination varied greatly among chemical and food types. The highest level of pesticide contamination was from the dichlorodiphenyltrichloroethane (DDT) metabolite p,p′- dichlorodiphenyldichloroethylene, which ranged from 0.028 ng/g wet weight (ww) in whole milk yogurt to 2.3 ng/g ww in catfish fillets. We found PCB congeners (28, 52, 101, 118, 138, 153, and 180) primarily in fish, with highest levels in salmon (PCB-153, 1.2 ng/g ww; PCB-138, 0.93 ng/g ww). For PFCs, we detected perfluorooctanoic acid (PFOA) in 17 of 31 samples, ranging from 0.07 ng/g in potatoes to 1.80 ng/g in olive oil. In terms of dietary intake, DDT and DDT metabolites, endosulfans, aldrin, PCBs, and PFOA were consumed at the highest levels. Conclusion Despite product bans, we found POPs in U.S. food, and mixtures of these chemicals are consumed by the American public at varying levels. This suggests the need to expand testing of food for chemical contaminants.",
"title": "Perfluorinated Compounds, Polychlorinated Biphenyls, and Organochlorine Pesticide Contamination in Composite Food Samples from Dallas, Texas, USA"
},
{
"docid": "MED-1557",
"text": "AIM: To systematically review data from different countries on population intakes of total fat, saturated fatty acids (SFA) and polyunsaturated fatty acids (PUFA), and to compare these to recommendations from the Food and Agriculture Organization of the United Nations/the World Health Organization (FAO/WHO). METHODS: Data from national dietary surveys or population studies published from 1995 were searched via MEDLINE, Web of Science and websites of national public health institutes. RESULTS: Fatty acid intake data from 40 countries were included. Total fat intake ranged from 11.1 to 46.2 percent of energy intake (% E), SFA from 2.9 to 20.9% E and PUFA from 2.8 to 11.3% E. The mean intakes met the recommendation for total fat (20-35% E), SFA (<10% E) and PUFA (6-11% E) in 25, 11 and 20 countries, respectively. SFA intake correlated with total fat intake (r = 0.76, p < 0.01) but not with PUFA intake (r = 0.03, p = 0.84). Twenty-seven countries provided data on the distribution of fatty acids intake. In 18 of 27 countries, more than 50% of the population had SFA intakes >10% E and in 13 of 27 countries, the majority of the population had PUFA intakes <6% E. CONCLUSIONS: In many countries, the fatty acids intake of adults does not meet the levels that are recommended to prevent chronic diseases. The relation between SFA and PUFA intakes shows that lower intakes of SFA in the populations are not accompanied by higher intakes of PUFA, as is recommended for preventing coronary heart disease.",
"title": "Intake of fatty acids in general populations worldwide does not meet dietary recommendations to prevent coronary heart disease: a systematic review..."
},
{
"docid": "MED-4702",
"text": "OBJECTIVES: The aim of the study was to evaluate the possible influence of acetic acid (administered as vinegar) on the postprandial glucose and insulin responses, and the potential involvement of a modified gastric emptying rate was studied by use of paracetamol as a marker. DESIGN: The white bread reference meal as well as the corresponding meal supplemented with vinegar had the same content of starch, protein and fat. The meals were served in the morning after an over-night fast and in random order. Capillary blood samples for analysis of glucose, insulin and paracetamol were collected postprandially. SETTING: The study was performed at the Department of Applied Nutrition and Food Chemistry, Lund University, Sweden. SUBJECTS: Ten healthy volunteers, seven women and three men, aged 22-51 y, with normal body mass indices were recruited. RESULTS: The presence of acetic acid, given as vinegar, significantly reduced the postprandial glucose (GI=64) and insulin responses (II=65) to a starchy meal. As judged from lowered paracetamol levels after the test meal with vinegar, the mechanism is probably a delayed gastric emptying rate. CONCLUSIONS: Fermented foods or food products with added organic acids should preferably be included in the diet in order to reduce glycaemia and insulin demand.",
"title": "Delayed gastric emptying rate may explain improved glycaemia in healthy subjects to a starchy meal with added vinegar."
},
{
"docid": "MED-4165",
"text": "Ergothioneine is a native membrane-impermeable thiol compound that is specifically accumulated in cells via the organic cation transporter OCTN1. In humans, OCTN1 and ergothioneine have been implicated in the etiopathogenesis of autoimmune disorders. However, available evidence about dietary sources and the functional role of ergothioneine in human physiology is scarce. Here, we analyzed the ergothioneine content in common foods using liquid chromatography tandem-mass spectrometry. Additionally, we assessed the protective potency of ergothioneine against various oxidative stressors in OCTN1-expressing cells in comparison with the main intracellular thiol antioxidant glutathione by evaluating cell viability with the MTT reduction assay. Only some food contained ergothioneine with highest concentrations detected in specialty mushrooms, kidney, liver, black and red beans, and oat bran. Ergothioneine exhibited cell protection only against copper(II)-induced toxicity but was far less potent than glutathione, indicting that ergothioneine is not involved in the intracellular antioxidant thiol defense system.",
"title": "Dietary sources and antioxidant effects of ergothioneine."
},
{
"docid": "MED-2036",
"text": "The prevalence of allergic-related diseases, food intolerance, and chemical sensitivities in both the pediatric and adult population has increased dramatically over the last two decades, with escalating rates of associated morbidity. Conditions of acquired allergy, food intolerance and chemical hypersensitivity are frequently the direct sequelae of a toxicant induced loss of tolerance (TILT) in response to a significant initiating toxic exposure. Following the primary toxicant insult, the individuals become sensitive to low levels of diverse and unrelated triggers in their environment such as commonly encountered chemical, inhalant or food antigens. Among sensitized individuals, exposure to assorted inciting stimuli may precipitate diverse clinical and/or immune sequelae as may be evidenced by clinical symptoms as well as varied lymphocyte, antibody, or cytokine responses in some cases. Recently recognized as a mechanism of disease development, TILT and resultant sensitivity-related illness (SRI) may involve various organ systems and evoke wide-ranging physical or neuropsychological manifestations. With escalating rates of toxicant exposure and bioaccumulation in the population-at-large, an increasing proportion of contemporary illness is the direct result of TILT and ensuing SRI. Avoidance of triggers will preclude symptoms, and desensitization immunotherapy or immune suppression may ameliorate symptomatology in some cases. Resolution of SRI generally occurs on a gradual basis following the elimination of bioaccumulated toxicity and avoidance of further initiating adverse environmental exposures. As has usually been the case throughout medical history whenever new evidence regarding disease mechanisms emerges, resistance to the translation of knowledge abounds. Copyright © 2010 Elsevier B.V. All rights reserved.",
"title": "Sensitivity-related illness: the escalating pandemic of allergy, food intolerance and chemical sensitivity."
},
{
"docid": "MED-4870",
"text": "Anatoxin-a is a potent neurotoxin produced by several species of cyanobacteria. This alkaloid may cause fatal intoxication to exposed organisms and this has raised concerns over the increasing popularity of food supplements containing cyanobacteria. These are being marketed with alleged health properties for animal and human consumption. These supplements most commonly contain the genera Spirulina (Arthrospira) and Aphanizomenon and their consumption represent a potential route for anatoxin-a exposure in cases where adequate quality control is not undertaken. In this work, several dietary supplements containing cyanobacteria from different commercial suppliers were evaluated for the presence of anatoxin-a by high performance liquid chromatography with fluorescence detection. Additionally, the presence of the previously derivatized anatoxin-a was confirmed by using Gas chromatography-mass spectrometry. A total of 39 samples were analysed in the study. Results showed that three of the samples (7.7%) contained anatoxin-a, at concentrations ranging from 2.50 to 33 microg g(-1). Quality control of cyanobacterial food supplements is required to avoid potential health effects in humans and animals.",
"title": "First detection of anatoxin-a in human and animal dietary supplements containing cyanobacteria."
},
{
"docid": "MED-1098",
"text": "The first U.S. nationwide food sampling with measurement of dioxins, dibenzofurans, and coplanar, mono-ortho and di-ortho polychlorinated biphenyls (PCBs) is reported in this study. Twelve separate analyses were conducted on 110 food samples divided into pooled lots by category. The samples were purchased in 1995 in supermarkets in Atlanta, GA, Binghamton, NY, Chicago, IL, Louisville, KY, and San Diego, CA. Human milk also was collected to estimate nursing infants' consumption. The food category with highest World Health Organization (WHO) dioxin toxic equivalent (TEQ) concentration was farm-grown freshwater fish fillet with 1.7 pg/g, or parts per trillion (ppt), wet, or whole, weight. The category with the lowest TEQ level was a simulated vegandiet, with 0.09 ppt. TEQ concentrations in ocean fish, beef, chicken, pork, sandwich meat, eggs, cheese, and ice cream, as well as human milk, were in the range O.33 to 0.51 ppt, wet weight. In whole dairy milk TEQ was 0.16 ppt, and in butter 1.1 ppt. Mean daily intake of TEQ for U.S. breast-fed infants during the first year of life was estimated at 42 pg/kg body weight. For children aged 1-11 yr the estimated daily TEQ intake was 6.2 pg/kg body weight. For males and females aged 12-19 yr, the estimated TEQ intake was 3.5 and 2.7 pg/kg body weight, respectively. For adult men and women aged 20-79 yr, estimated mean daily TEQ intakes were 2.4 and 2.2 pg/kg body weight, respectively. Estimated mean daily intake of TEQ declined with age to a low of 1.9 pg/kg body weight at age 80 yr and older. For all ages except 80 yr and over, estimates were higher for males than females. For adults, dioxins, dibenzofurans, and PCBs contributed 42%, 30%, and 28% of dietary TEQ intake, respectively. DDE was also analyzed in the pooled food samples.",
"title": "Intake of dioxins and related compounds from food in the U.S. population."
},
{
"docid": "MED-2423",
"text": "OBJECTIVE: Breast cancer is the most common type of cancer in women worldwide. Several studies have examined the role of single nutrients and food groups in breast cancer pathogenesis but fewer investigations have addressed the role of dietary patterns. Our main objective was to identify the relationship between major dietary patterns and breast cancer risk among Iranian women. DESIGN: Hospital-based case-control study. SETTING: Shohada Teaching Hospital, Tehran, Iran. SUBJECTS: Overall, 100 female patients aged 30-65 years with breast cancer and 174 female hospital controls were included in the present study. Dietary intake was assessed using a valid and reliable semi-quantitative FFQ consisting of 168 food items. RESULTS: Two dietary patterns were identified explaining 24·31 % of dietary variation in the study population. The 'healthy' food pattern was characterized by the consumption of vegetables, fruits, low-fat dairy products, legumes, olive and vegetable oils, fish, condiments, organ meat, poultry, pickles, soya and whole grains; while the 'unhealthy' food pattern was characterized by the consumption of soft drinks, sugars, tea and coffee, French fries and potato chips, salt, sweets and desserts, hydrogenated fats, nuts, industrial juice, refined grains, and red and processed meat. Compared with the lowest tertile, women in the highest tertile of the 'healthy' dietary pattern score had 75 % decreased risk of breast cancer (OR = 0·25, 95 % CI 0·08, 0·78), whereas women in the highest tertile of the 'unhealthy' dietary pattern had a significantly increased breast cancer risk (OR = 7·78, 95 % CI 2·31, 26·22). CONCLUSIONS: A healthy dietary pattern may be negatively associated with breast cancer risk, while an unhealthy dietary pattern is likely to increase the risk among Iranian women.",
"title": "Dietary patterns and breast cancer risk among women."
}
] |
3754
|
What happens to my savings if my country defaults or restructures its debt?
|
[
{
"docid": "598030",
"text": "In theory, anything can happen, and the world could end tomorrow. However, with a reasonably sane financial plan you should be able to ride this out. If the government cannot or won't immediately pay its debt in full, the most immediate consequence is that people are going to be unwilling to lend any more money in future, except at very high rates to reflect the high risk of future default. Presumably the government has got into this state by running a deficit (spending more than they collect in tax) and that is going to have to come to an abrupt end. That means: higher taxes, public service retrenchments and restrictions of service, perhaps cuts to social benefits, etc. Countries that get into this state typically also have banks that have lent too much money to risky customers. So you should also expect to see some banks get into trouble, which may mean customers who have money on deposit will have trouble getting it back. In many cases governments will guarantee deposits, but perhaps only up to a particular ceiling like $100k. It would be very possible to lose everything if you have speculative investments geared by substantial loans. If you have zero or moderate debt, your net wealth may decrease substantially (50%?) but there should be little prospect of it going to zero. It is possible governments will simply confiscate your property, but I think in a first-world EU country this is fairly unlikely to happen to bank accounts, houses, shares, etc. Typically, a default has led to a fall in the value of the country's currency. In the eurozone that is more complex because the same currency is used by countries that are doing fairly well, and because there is also turbulence in other major currency regions (JPY, USD and GBP). In some ways this makes the adjustment harder, because debts can't be inflated down. All of this obviously causes a lot of economic turbulence so you can expect house prices to fall, share prices to gyrate, unemployment to rise. If you can afford it and come stomach the risk, it may turn out to be a good time to buy assets for the long term. If you're reasonably young the largest impact on you won't be losing your current savings, but rather the impact on your future job prospects from this adjustment period. You never know, but I don't think the Weimar Republic wheelbarrows-of-banknotes situation is likely to recur; people are at least a bit smarter now and there is an inflation-targeting independent central bank. I think gold can have some room in a portfolio, but now is not the time to make a sudden drastic move into it. Most middle class people cannot afford to have enough gold to support them for the rest of their life, though they may have enough for a rainy day or to act as a balancing component. So what I would do to cope with this is: be well diversified, be sufficiently conservatively positioned that I would sleep at night, and beyond that just ride it out and try not to worry too much.",
"title": ""
},
{
"docid": "379419",
"text": "Remove your money. If you do not need this money for some time, you can convert it to Gold, and now is a good time to buy. Gold is not expected to decrease much in price as we're already at the bottom of the employment cycle and the Depression is already begun and will take about two years to grip the world.",
"title": ""
},
{
"docid": "122513",
"text": "I am going to add in an opinion here from the Wall Street Journal that I read this morning in What's at Stake in the Greek Vote, in light of current events and elections in Greece. The article claims that if the election results make it sound like a break from the Euro is imminent then ... we will see a full-fledged bank run. Greek banks would collapse ... The market exchange-rate would likely be two or three drachmas to the euro, which would double or triple the Greek price of imported goods within a few days. Prices of assets, including real-estate assets, would crumble. Those who moved their deposits abroad would be able to buy these assets cheaply, leading to a significant, regressive redistribution of Greek wealth. In short, you'd lose two-thirds of your savings unless you were storing them somewhere safe from the conversion. The article also predicts difficulty importing goods (other nations will demand to be paid in euro, not drachma) leading to disruption of trade and various supply shortages. I will note that the predictions here seem to be in opposition to some other advice here which suggests that real estate will be an effective hedge.",
"title": ""
},
{
"docid": "540553",
"text": "\"This question is different because you are asking for actual advice vs. a more academic, \"\"what if\"\" scenario. The answer that I'll give will be different, and similar to another recent question on a similar vein. Basically, if you're living in a European country that's effectively in default and in need of a bailout, the range of things that can happen is difficult to predict... the fate of countries like Ireland and Greece, whatever the scenario, will be economic and social upheaval. But, this isn't the end of the world either... it's happened before and will happen again. As an individual, you need to start investing defensively in a manner appropriate for your level of wealth. Things to think about: I'd suggest reading \"\"A Free Nation Deep in Debt: The Financial Roots of Democracy\"\"\"",
"title": ""
},
{
"docid": "575359",
"text": "First question: Any, probably all, of the above. Second question: The risk is that the currency will become worth less, or even worthless. Most will resort to the printing press (inflation) which will tank the currency's purchasing power. A different currency will have the same problem, but possibly less so than yours. Real estate is a good deal. So are eggs, if you were to ask a Weimar Germany farmer. People will always need food and shelter.",
"title": ""
},
{
"docid": "235322",
"text": "Best thing to do is convert your money into something that will retain value. Currency is a symbol of wealth, and can be significantly devalued with inflation. Something such as Gold or Silver might not allow you to see huge benefit, but its perhaps the safest bet (gold in particular, as silver is more volatile), as mentioned above, yes you do pay a little above spot price and receive a little below spot when and if you sell, but current projections for both gold and silver suggest that you won't lose money at least. Safe bet. Suggesting it is a bad idea at this time is just silly, and goes against the majority of advisers out there.",
"title": ""
},
{
"docid": "309358",
"text": "\"The biggest risk you have when a country defaults on its currency is a major devaluation of the currency. Since the EURO is a fiat currency, like almost all developed nations, its \"\"promise\"\" comes from the expectation that its union and system will endure. The EURO is a basket of countries and as such could probably handle bailing out countries or possibly letting some default on their sovereign debt without killing the EURO itself. A similar reality happens in the United States with some level of regularity with state and municipal debt being considered riskier than Federal debt (it isn't uncommon for cities to default). The biggest reason the EURO will probably lose a LOT of value initially is if any nation defaults there isn't a track record as to how the EU member body will respond. Will some countries attempt to break out of the EU? If the member countries fracture then the EURO collapses rendering any and all EURO notes useless. It is that political stability that underlies the value of the EURO. If you are seriously concerned about the risk of a falling EURO and its long term stability then you'd do best buying a hedge currency or devising a basket of hedge currencies to diversify risk. Many will recommend you buy Gold or other precious metals, but I think the idea is silly at best. It is not only hard to buy precious metals at a \"\"fair\"\" value it is even harder to sell them at a fair value. Whatever currency you hold needs to be able to be used in transactions with ease. Doesn't do you any good having $20K in gold coins and no one willing to buy them (as the seller at the store will usually want currency and not gold coins). If you want to go the easy route you can follow the same line of reasoning Central Banks do. Buy USD and hold it. It is probably the world's safest currency to hold over a long period of time. Current US policy is inflationary so that won't help you gain value, but that depends on how the EU responds to a sovereign debt crisis; if one matures.\"",
"title": ""
},
{
"docid": "304007",
"text": "\"The danger to your savings depends on how much sovereign debt your bank is holding. If the government defaults then the bank - if it is holding a lot of sovereign debt - could be short funds and not able to meet its obligations. I believe default is the best option for the Euro long term but it will be painful in the short term. Yes, historically governments have shut down banks to prevent people from withdrawing their money in times of crisis. See Argentina circa 2001 or US during Great Depression. The government prevented people from withdrawing their money and people could do nothing while their money rapidly lost value. (See the emergency banking act where Title I, Section 4 authorizes the US president:\"\"To make it illegal for a bank to do business during a national emergency (per section 2) without the approval of the President.\"\" FDR declared a banking holiday four days before the act was approved by Congress. This documentary on the crisis in Argentina follows a woman as she tries to withdraw her savings from her bank but the government has prevented her from withdrawing her money.) If the printing press is chosen to avoid default then this will allow banks and governments to meet their obligations. This, however, comes at the cost of a seriously debased euro (i.e. higher prices). The euro could then soon become a hot potato as everyone tries to get rid of them before the ECB prints more. The US dollar could meet the same fate. What can you do to avert these risks? Yes, you could exchange into another currency. Unfortunately the printing presses of most of the major central banks today are in overdrive. This may preserve your savings temporarily. I would purchase some gold or silver coins and keep them in your possession. This isolates you from the banking system and gold and silver have value anywhere you go. The coins are also portable in case things really start to get interesting. Attempt to purchase the coins with cash so there is no record of the purchase. This may not be possible.\"",
"title": ""
},
{
"docid": "231521",
"text": "My 0,02€ - I probably live in the same country as you. Stop worrying. The Euro zone has a 100.000€ guaranty deposit. So if any bank should fail, that's the amount you'll receive back. This applies to all bank accounts and deposits. Not to any investments. You should not have more than 100.000€ in any bank. So, lucky you, if you have more than that money, divide between a number of banks. As for the Euro, there might be an inflation, but at this moment the USA and China are in a currency battle that 'benefits' the Euro. Meaning you should not invest in dollars or yuan at this time. Look for undervalued currency to invest in as they should rise against the Euro.",
"title": ""
}
] |
[
{
"docid": "218045",
"text": "\"What EU wanted to force Cyprus to do is to break the insurance contract the government has with the bank depositors. The parliament rightfully refused, and it didn't pass. In the EU, and Cyprus as part of it, all bank deposits are insured up to 100,000EUR by the government. This is similar to the US FDIC insurance. Thus, requiring the \"\"small\"\" (up to 100K) depositors to participate in the bank reorganization means that the government breaks its word to people, and effectively defaults. That is exactly what the Cyprus government wanted to avoid, the default, so I can't understand why the idea even came up. Depositors of more than 100k are not guaranteed against bank failures, and indeed - in Cyprus these depositors will get \"\"haircuts\"\". But before them, first come shareholders and bondholders who would be completely wiped out. Thus, first and foremost, those who failed (the bank owners) will be the first to pay the price. However, governments can default. This happened in many places, for example in Russia in the 90's, in Argentina in 2000's (and in fact numerous times during the last century), the US in the 1930's, and many other examples - you can see a list in Wikipedia. When government defaults on its debts, it will not pay some or all of them, and its currency may also be devaluated. For example, in Russia in 1998 the currency lost 70% of its value against the USD within months, and much of the cash at hands of the public became worthless overnight. In the US in 1933 the President issued an executive order forbidding private citizens keeping gold and silver bullions and coins, which resulted in dollar devaluation by about 30% and investors in precious metals losing large amounts of money. The executive order requiring surrender of the Treasury gold certificates is in fact the government's failure to pay on these obligations. While the US or Russia control their own currency, European countries don't and cannot devaluate the currency as they wish in order to ease their debts. Thus in Euro-zone the devaluation solutions taken by Russia and the US are not possible. Cyprus cannot devaluate its currency, and even if it could - its external debt would not likely to be denominated in it (actually, Russian debt isn't denominated in Rubles, that's why they forced restructuring of their own debt, but devaluating the currency helped raising the money from the citizens similarly to the US seizing the gold in 1930's). Thus, in case of Cyprus or other Euro-zone countries, direct taxes is the only way to raise money from the citizens. So if you're in a country that controls its own currency (such as the US, Russia, Argentina, etc) and especially if the debt is denominated in that currency (mainly the US) - you should be worried more of inflation than taxes. But if you're in the Euro-zone and your country is in troubles (which is almost any country in the zone) - you can expect taxes. How to avoid that? Deal with your elected officials and have them fix your economy, but know that you can't just \"\"erase\"\" the debt through inflation as the Americans can (and will), someone will have to pay.\"",
"title": ""
},
{
"docid": "526384",
"text": "What happens to consumer debt if a country defaults on its debt? Nothing, just as nothing happens to your debt when your neighbor defaults. If you have debts that have floating interest rates - those may (and probably will) hike. how will a debt default by a country affect government-backed loans such as mortgages and student loans? Those that are already closed will probably not be affected, as you've got the money already and signed the loan agreement. Those that are not closed - will probably be delayed or not funded at all. However, if any of the debts allows the debtor to request an early collection (which I think is rather rare on the consumer market) - someone else's default may lead to the debtor's request for the money earlier than expected.",
"title": ""
},
{
"docid": "501376",
"text": "\"Can't declare bankruptcy isn't the same as \"\"can't default\"\". Bankruptcy is a specific legal process for discharging or restructuring debts. If Illinois can't declare bankruptcy, that means it will still owe you the money for the bonds no matter what, but it doesn't guarantee that it will actually pay you what it owes. If Illinois should run out of money to pay what's due on its bonds, then it will default. Unlike the federal government, Illinois can't print money to make the payments.\"",
"title": ""
},
{
"docid": "306390",
"text": "\"> I think a the thing with depression and recession is just what he uses to define those economic statuses. He says at the begining that his thinking on the subject is what he uses and might not be conventional. I see. But if the severity of economic recessions/depressions can be categorized by, say, what % of debt defaults or is restructured in a certain period of time, that actually would be a convenient way to think about different recession events intuitively (instead of just the degree to which GDP goes up or down). And I wonder if defaults/debt restructurings are a leading or lagging indicator of a recession. > For the different methods of depression recovery I beleive he was trying to say that the path to a \"\"beautiful devleraging\"\" requires balance. Certaintly the deflationary tactics have there own merits, and are not solely for the purpose of offsetting the inflationary methods, but a balance of everything is the most crucial factor for an efficient recovery. Austerity is deflationary (and I'm not sure there are any mainstream/academic economists who support austerity during a recession...) but, again, I have serious doubts whether debt reduction and wealth distribution can be called deflationary. Especially wealth distribution, which is basically the same thing as fiscal spending (which is included in the \"\"print money\"\" inflationary category in the video) combined with regressive taxes. I would think that monetary easing and fiscal stimulus (both inflationary) help employment recover, and once employment recovers enough, inflation can rise. Once inflation is expected to rise too much, then you can crank up interest rates/lower fiscal spending. I don't think you really need to worry about adding in deflation for a \"\"balance\"\" when trying to recover an economy. Hyperinflation happens only in extreme cases and stagflation, as far as I know, is a technical case that is hard to explain in a video like this. Certainly, austerity is unlikely to help stagflation.\"",
"title": ""
},
{
"docid": "538582",
"text": "Andrew Lilico has a likely scenario for when Greece defaults on its sovereign debt: What happens when Greece defaults. Here are a few things: Every bank in Greece will instantly go insolvent. The Greek government will nationalise every bank in Greece. The Greek government will forbid withdrawals from Greek banks. To prevent Greek depositors from rioting on the streets, Argentina-2002-style (when the Argentinian president had to flee by helicopter from the roof of the presidential palace to evade a mob of such depositors), the Greek government will declare a curfew, perhaps even general martial law. Greece will redenominate all its debts into “New Drachmas” or whatever it calls the new currency (this is a classic ploy of countries defaulting) The New Drachma will devalue by some 30-70 per cent (probably around 50 per cent, though perhaps more), effectively defaulting 0n 50 per cent or more of all Greek euro-denominated debts. As Megan McArdle says, there's more at the link, all depressing. I think you're focusing too much on Greece leaving the euro and not enough on why Greece would leave the euro. Greece would leave the euro precisely so that it could pay back its debt in a new currency worth less than valuable euros. The new currency will devalue, since that's the point of leaving. Along the way the government forces its citizens to take the new currency. The money they have in Greek banks will be converted to the new currency: The citizens don't have a choice to keep their euros.",
"title": ""
},
{
"docid": "252227",
"text": "\"The only party that can pay back a government bond is the government that issued it itself. In the case of Argentina, US vulture funds have won cases against it, but it has yet to pay. The best one can do to collect is to sue in a jurisdiction that permits and hope to seize the defaulted government's assets held in such jurisdiction. One could encourage another state to go to war to collect, but this is highly unlikely since a state that doesn't repay is probably a poor state with nothing much to loot; besides, most modern governments do not loot the conquered anymore. Such a specific eventuality hasn't happened in at least a lifetime, anyways. It is highly unlikely that any nation would be foolish enough to challenge the United States considering its present military dominance. It is rare for nations with medium to large economies to spurn their government obligations for long with Argentina as the notable exception. Even Russia became current when they spontaneously disavowed their government debt during the oil collapse of 1998. Countries with very small economies such as Zimbabwe are the only remaining nations that try to use their central banks to fund debt repayments if they even repay at all, but they quickly see that the destruction caused by hyperinflation neither helps with government debt nor excessive government expenditure. Nevertheless, it could be dangerous to assume that no nation would default on its debt for any period of time, and the effects upon countries with defaulted government debt show that it has far reaching negative consequences. If the US were to use its central bank to repay its government obligations, the law governing the Federal Reserve would have to be changed since it is currently mandated to \"\"maintain long run growth of the monetary and credit aggregates commensurate with the economy's long run potential to increase production, so as to promote effectively the goals of maximum employment, stable prices and moderate long-term interest rates.\"\" The United States Treasury has no power over the Federal Reserve thus cannot force the Federal Reserve to betray its mandate by purchasing government debt. It should be noted that while Japan has a government debt twice its GDP, it also has a persistent slight deflation which has produced incredibly low interest rates, allowing it to finance government debt more easily, a situation the US does not enjoy. For now, the United States seems to be able to pay expenditures and finance at low interest rates. At what ratio of government debt to GDP that would cause interest rates to climb thus put pressure on the US's ability to repay does not seem to be well known.\"",
"title": ""
},
{
"docid": "454629",
"text": "\"Its fraudulent because it is feeds on new investment to pay the old investors, the EXACT definition of a Ponzi. And it now is contingent on the faith of the US, as with most other debts. There is no \"\"trust fund\"\" of this wealth sitting waiting for us if the USA fails. But do tell me, how is SS not a ponzi scheme? Does it not use new money to pay the old? If the new money ran out, would it not default on its debts (in the future)? And what part of the constitution says the US government should collect some of my wages and save it for me for later? You do know, some people have opted out of SS? Even the US government will not take the fight to court. They know its a sham.\"",
"title": ""
},
{
"docid": "321842",
"text": "Today the rates are arrived simply on the basis of demand and supply. Historically rates were pegged to Gold, when all currencies were printed depending on the Gold reserves. So if one country printed 100 units of currency of a 1gm of gold and other country 10 units of currency for 1 gm of gold, the rate would be 1:10. However In the seventies with shortages of Gold and other reasons, USD became the default standard, so the rate started being pegged to the USD reserves the countries started maintaining. However later in the early eighties, US backing out, the rate purely started getting pegged to market demand and supply. So for most currencies there was a default rate to begin with and today its changed ... Incase of USD/EUR, the initial rate was determined by the weighted average of the currencies that it sought to replace. After that its been market supply and demand. Since most of the trade in international market is US denominated, largest being Oil, each country has created a huge reserves of USD. So technically if China were to bank half its USD denominated treasury bills, the USD would come crashing down, but then China itself would be at disadvantage as its value of USD its holding would become less and it cannot buy the same items. Hence all countries keep hording USD and this means US if they print more money, the value will not come down, because it that happens, all countries holding USD would loose their value of reserve. In essence a country can print as much as currency it wants if all(majority) its debts and trades are denominated in local currencies. This is 100% true for US and hence it can get away by printing money. This is also true to a large extent for Japan as bulk of its Debts are denominated in JPY.",
"title": ""
},
{
"docid": "559618",
"text": "\"Somehow I just stumbled onto this thread... > You essentially robbed the person holding the debt (since you promised to pay it off). Depends on leverage, with fractional reserve lending. Banks are permitted to loan out 30x their actual assets, or more. If I have $1 but can loan out $30, and anything more than $1 gets paid back, I haven't lost any money. In addition, I can write off the amount defaulted, *and the government will pay me back* for certain types of loans. With student loans, since they are almost impossible to discharge, gov't will pursue the borrower for years and decades, and ultimately collect more interest. Here is an article on it: http://online.wsj.com/article/SB10001424052748704723104576061953842079760.html > According to Kantrowitz, the government stands to earn $2,010.44 more in interest from a $10,000 loan that defaulted than if it had been paid in full over a 20-year term, and $6,522.00 more than if it had been paid back in 10 years. Alan Collinge, founder of borrowers' rights advocacy Student Loan Justice, said the high recovery rates provide a \"\"perverted incentive\"\" for the government to allow loans to go into default. Kantrowitz estimates the recovery rate would need to fall to below 50% in order for default prevention efforts to become more lucrative than defaults themselves. Not to mention: http://studentloanjustice.org/defaults-making-money.html > So essentially, the Department is given a choice: Either do nothing and get nothing, or outlay cash with the knowledge that this outlay will realize a 22 percent return, ultimately (minus the governments cost of money and collection costs). From this perspective, it is clear that based solely on financial motivations, and without specific detailed knowledge of the loan (i.e. borrower characteristics, etc.), the chooser would clearly favor the default scenario, for not only the return, but perhaps the potential savings in subsidy payment as well, And don't forget the penalties accruing to the person defaulting; they will probably have to move out of the country in order to escape collection. And let's factor in the huge ROI the lender sees by creating an indentured servant class. Plus, the gov't will issue as much currency as it wants, to make *itself* whole. And how much of a loss IS the loss, when the whole of the loan amount went right back into the local economy, paying professors, janitors, landlords, grocery stores, etc.? And don't forget all THOSE taxes (income and sale) that the gov't collects. Government will collect ~30%-50% of the loan immediately as income and sales tax, plus a portion of it every time the money changes hands (I pay income tax, then use some of my after-tax money to pay you for a product or service, and you still have to pay tax on that money, and so on). So it's more complicated than having \"\"robbed the person holding the debt\"\". Banks at 30x leverage don't lose money as long as they get back 1/30th of the total amount lent out, including interest, fees, and penalties, before considering write-offs and government repayment. In fact, the point of over-leverage is so you CAN make loans that have risk attached. If you could only lend what you actually had, you would have to stay away from anything risky because it would be too easy to lose money. Having virtual $ to bet means you can serve market segments that have higher risk. This makes MORE money for the banks, that's why they do it. They are already playing with funny money, so they don't lose any even if you default and move to another country. And the money you \"\"spent\"\" has also made its way back to them in various amounts, such as your professor's mortgage payments, auto loan, etc. Your taking on debt already helped the bank get its OTHER loans repaid. So, roughly speaking, if you took out $90,000 and $3,000 of that made its way back to the bank through various means, they haven't lost any money, because it only cost them $3,000 actual dollars in the first place.\"",
"title": ""
},
{
"docid": "395379",
"text": "I've kind of been there myself. I stretched my finances for the deposit on a house, and lived off my credit card for a few months to build up what I was short on the deposit. Add some unexpected car repairs, and I ended up with £10k on the card. The problem I had then was that interest on the card ran at around 20%, and although I could meet the interest payments I couldn't clear the £10k. I simply went and talked to my bank. In the UK there are some clear rules about banks giving customers a chance to restructure their debts. That's the BANK doing it, not some shady loan-shark. We went through my finances and established that in principle it was repayable. So I got a 2-year unsecured loan at around 5%, cleared the card, and spent the next 2 years paying off a loan that I could afford. My credit score is still aces. Forget the loan-sharks. Talk to your bank. If they're crap, talk to another bank. If no bank is going to help you, consider bankrupcy as per advice above. Debt restructuring companies are ALWAYS a con, no exceptions.",
"title": ""
},
{
"docid": "140947",
"text": "\"The US national debt isn't the problem. If the Bush-era tax cuts had been allowed to expire then US debt would have been paid off reasonably quickly. The CBO’s “baseline” budget forecast, which assumes that the cuts do indeed expire as planned, sees the deficit falling from 9.1% of GDP in 2010 to 2.5% in 2014. These are just the debts the US has already incurred. The problem is the future entitlements the US is promising to its soon-to-be-retired generation of Baby Boomers. Medicare, health insurance, and so on are all future costs that can be calculated fairly accurately when considering the size and earnings of the work-force relative to the size, longevity and health of the newly-retired. Governments can \"\"solve\"\" the problems of entitlements simply be reneging on their promises. The concern that investors have is that either entitlements will be paid by raising taxes (and so cutting profits and investment returns) or countries will simply default on their existing debts as their tax receipts run out. As Europe has shown (from French workers rioting about having to retire at 62, to British students rioting about paying their tuition fees), breaking promises has consequences for elected politicians too. Europe is already going rather painfully through this process of economic restructuring. The US will eventually come round as well. Just don't expect it to be painless. So keep your money and invest it wisely. No doubt that tax collectors will be round in a while to take their cut so you can make your contribution.\"",
"title": ""
},
{
"docid": "282196",
"text": "\"In general I don’t think you can blame the news stories. You can blame everyone’s preconceived notion that any sort of LBO or leveraged restructuring is the devil’s work. Every American is of course well-versed in the subject. From the Sealy example, you clearly have a journalist who has no idea what they are talking about. All you have is a cherry-picked summary of what took place. As such, the “finance scholars” jump in and explain how it’s all a giant scam. Bain LBO’d Sealy in 1997. As a part of that, it was saddled with ~$700m in debt. That of course is fodder for the \"\"finance scholars\"\" because they don't understand the benefits of debt and more generally how LBOs work, none of which are noted in the article. The article then notes that Sealy has recently encountered trouble. To the \"\"geniuses\"\" this is of course because of Romney's work and the ~$700m in debt. No one notices the fact that Bain unloaded this in 2004 for double what it paid for it. For those that did, the unloading was a textbook Bain scam. Bain unloaded this to KKR, perhaps the sharpest and most successful PE firm in history. Would KKR put $1.5b into this if it were a scam? According to the \"\"geniuses\"\", of course they would. How could Mitt Romney actually improve a business? No one looks at the fact that revenues were up considerably, margins had expanded tremendously, growth prospects were higher, and FCF yields were fantastic. This is why KKR bought the company, and this is what an LBO is supposed to be. I haven't done a ton of work on this case, it was before my time, but I would be very surprised if the growth wasn't accompanied by employee expansion as well. You also get the “I wish I had a way to just walk away from my debt” comment. I don’t even know where to begin explaining how asinine that is. Equity is subordinated to debt. That’s the definition of equity. The article also notes the one-sided-mattress idea, which is construed as Romney's giant scam to screw the average American while flipping this company and making his millions. The article of course didn't note that this one-sided mattress idea was a mere fraction of revenue. This was designed as an economy mattress, with an advertised shorter shelf life. Plus how can this be a scam? Would you go into the mattress store and pay the same amount for a mattress with only one side? If you would you deserve to get half of a mattress. So the crux of it is, this is in actuality an example of what an LBO should be. At least for Bain’s part. Bain took a business that was ripe for an LBO (reasonable steady FCF, low leverage), did the LBO, improved the business, and came out on top. What KKR did with it afterwords I have no idea. I would imagine it has more to do with deteriorating business conditions than the debt on its balance sheet. I work with restructurings over 100 hours a week. I of course don’t come up with the plans (I’m a lowly analyst building models and associated bitchwork) but I see just how brilliant these ideas are. In a lot of cases restructurings prevent the tripping of covenants and associated bankruptcy and allow for strategy to play out and for companies to grow. I can of course give a more detailed rant on the article, but I figured no one will read this anyway.\"",
"title": ""
},
{
"docid": "127268",
"text": "The prices seem very low even considering the risk? The prices are low because of the risk. Nothing happens to the banks if the sovereign defaults. However, the sovereign debt holders - lose some or all the money they lent to that sovereign. Incidentally, many banks invest in the treasury bonds of various countries, especially those they're located in. They also invest in other companies that rely on the government, or the currency. If that dependency is too high - the bank may fail. If the dependency is not high, or non-existent - the bank will survive. If the bank fails - yes, your shares will be wiped out, that's what happens with bankrupt companies. If you considering investing in banks in a country that you think may default - research them and see how much investments they have that will be affected by that default.",
"title": ""
},
{
"docid": "466310",
"text": ">The US government debt is how much USD the government has paid the US non-government in excess of what it's taxed them. Correct? Incorrect. The US debt/savings is the balance of credit the US government maintains with US banks, and foreign sovereigns/banks. Why do you need to say it another way? WTF is 'non-government' savings? Other than an academically retarded way of saying 'debt' of course? Its not a bad thing... unless interest rates rise. But this time is different, so that'll never happen. I'm sticking to my initial assessment. Fairyland.",
"title": ""
},
{
"docid": "580259",
"text": "\"Is there more on where Dalio gets his definitions for the short-term debt cycle (5-8 years or so) and \"\"deleveraging\"\" and the long-term debt cycle (75-100 years)? (or his evidence that separates the two)? At one point 18:10, he says the difference is that in a deleveraging, interest rates hit 0 and can no longer go lower, but I don't know if that works as a definition per se. There are other things that central banks do when interest rates hit 0, like buy up assets (which he does mention and include in the \"\"print money\"\" category of things that can be done during a deleveraging). And one of the deleveragings he cites, England in the 1950s, according to Wikipedia was due to difficulty in transitioning out from war production, and according to [this excel file](http://www.bankofengland.co.uk/statistics/Documents/rates/baserate.xls) from the Bank of England on historical rates, it doesn't say interest rates went to 0 at that time (unless Dalio is referring to another point in history when he cites 1950s England). 20:30 His definition of a depression is when debt restructuring or defaults happen. Interesting. What I learned was that there isn't really a hard and fast definition for recessions and depressions (e.g. a recession is two quarters of negative growth in a row and a depression is just a reeeaallly bad/long recession). And I don't think I recall encountering in the past an attempt to define what a \"\"deleveraging\"\" event of an economy is. 24:30 Is debt reduction and redistribution of wealth deflationary? I think it depends on how much the debt reduction or redistribution hurts the spending of the lender or wealthy versus how much it helps the spending of the borrower or the poor. Both are actually similarly \"\"giving some from the haves to the have nots,\"\" and especially redistribution of wealth is similar to fiscal spending, which is mentioned 25:30 as a valid inflationary way to try to help the economy. 26:00 Are deflationary methods (say, austerity) needed to balance out the inflationary methods (central bank buying assets and fiscal spending)? Aren't central bank (interest rates, quantitative easing) and the government (fiscal policy) still the main things that move inflation or deflation? I would think that debt reduction and redistribution of wealth are good when needed, but I wouldn't think you would do those things *mainly* for their (supposed, see above for my doubts) deflationary effects. Still, a very interesting video and one of the best presented videos on a difficult subject.\"",
"title": ""
},
{
"docid": "44360",
"text": "Government purchases of mortgages simply transfers the debt burden from households to the sovereign. Taxes pay sovereign debt (65% of whom are homeowners anyway). No debt has been restructured -- it's now paid via taxes instead of monthly mortgage payments -- and those paying include persons who responsibly avoided housing speculation. The U.S. has a debt-to-GDP ratio just shy of the critical point of 90%. Purchasing $10 trillion in mortgage debt (about a year of GDP) would put the U.S. on an inexorable path towards insolvency and inflation. There are all sorts of other risks (loss of a risk-free asset, moral hazard, nationalization of the housing industry, etc.) but this should make the point clear that it's not a good idea. There are only three ways to reduce debt: 1) default, 2) restructure, or 3) lower the real debt burden by de-valuing currency in which the debt is denominated.",
"title": ""
},
{
"docid": "111391",
"text": "\"I will say in advance this is not a great answer, but I had a similar experience when I owned a CIT bond that defaulted. I ended up getting stock plus 5 newly issued bonds as a replacement for my defaulted bond. My broker had no clue on cost basis and didn't even try for the new securities, I called the \"\"hotline\"\" setup about CIT default and they knew nothing, and finally I read all the paperwork around the restructuring but it was less than transparent. So in the end I ended up claiming everything as a wash, no gain/no loss - which probably screwed me in the end as I believe I ended up down. It was a very small position for me and was not worth the headache :(\"",
"title": ""
},
{
"docid": "322582",
"text": "I'm not saying that they shouldn't be allowed to default. What I'm saying is that if they can't pay back their debts then they should default. The article makes it sound like Argentina deserves to be let off the hook and pay back only a portion of its debt. In the short term this seems appealing because the investors get back some of the money as opposed to none and Argentina gets to keep it's economy intact. However this sets a dangerous precedent in the long run because countries know they have this out and may issue bonds expecting not to pay the full amount. I think it is good that Argentina is being made an example of, this way countries will think twice before borrowing money they may not be able to pay back and will lead to more stability in the long run.",
"title": ""
},
{
"docid": "569207",
"text": "\">We also have the highest expenditures as a percent of GDP than any other nation. Needless to say we spend a LOT on health care also. That is in large part do to insane healthcare costs passed on to the consumers by the aca. Healthcare spending has increased on average 1.5% annually since 2009 where as the highest growth in spending from 1991 until 2006 was 1.3% (im willing to admit my research may be incomplete or inaccurate here as the available rescources are pretty limited in my short time researching) >we do have arguably the best health care services in the world... that is mostly only true if you are very wealthy. Thats a dumb statement leftists make. There is no excuse to not put yourself in debt for the best healthcare possible. Idk about you but I'd rather be in a lot of debt getting first rate healthcare than get affordable care from a 2nd rate community college doctor. Did you also know that medical debt doesnt effect your credit score so even if you \"\"default\"\" on medical debts it doesnt effect any part of your life. so why wouldnt you go in debt and then slowly pay off that debt with no fear of negative repercussions for not paying? >When you break it down on results per dollar spent, the US doesn't even break the top 20. When you break it down on infant mortality, and life expectancy, we have been on a backward slide for a while now (although those rates improved for the short while that the ACA has been in effect, as have the net increase in costs). At the end of the day, the cost of health care has grown 3X faster than inflation, and 20X faster than the average income for over 30 years now. So, no, health care in this country is not the best to the average person. I dont have health insurance and an ER visit with xrays costs me less out of pocket than 90% of the country why is that? Do you think it has to do with the fact that with the aca hospitals know they are getting paid with 0 questioning on pricing so charge whatever they want and with me they think \"\"shit this guy might not ever pay us lets just give him a decent price and get some money from him because all we can do is send his bill to collections\"\" you clearly dont know how the system works especially because you think its my responsibility to provide you with health insurance. You keep saying i need to travel and experience the world when all you need to do is go to google and look at what a wonderful job Switzerland does with their healthcare. The swiss do everything better, They have some of the best services in the world and a very affordable healthcare plan with many options that is affordable to the tax payers unlike the ACA. You have a very clear Scandinavian bias as im assuming you're a bernie supporter who loves democratic socialism despite all of its short comings. >And yes, Space X has been able to estimate a savings of $300M less... Commercial does a great job of expanding on the research and knowledge that has come from government sponsored R&D. You see that in every modern technological advancement - from the internet, cellular phones, GPS, medical procedures, etc. There are so many modern inventions that have sprung from government patents and government research programs. This is the dumbest statement youve made this entire time. The notion that inventions that were made on the governments dime (my dime) is somehow the product of the government is asinine at best. Youre operating under the assumption that these inventions wouldnt have been made without government funding which is false. They all would have been made on a smaller budget granted maybe a little bit further down the road but not by much considering technology has expanded (with no help from any government) more in the last 20 years than in the prior 200 because thats what technology does it makes life easier for everyone and almost innovates itself. Take apple for instance where is all the government funding they recieved to be one of the most innovative companies in human history or microsoft? Yiou can max 10 things government funding invented when i can walk into your house and point out 10000 things the government had no hand in at all.\"",
"title": ""
},
{
"docid": "583903",
"text": "\"On contrary of what Mike Scott suggested, I think in case of EURO DOOM it's a lot safer if your savings were changed into another currency in advance. Beware that bringing your money into an EURO CORE country (like Finland, Austria, Germany, Nethereland) it's useful if you think those banks are safer, but totally useless to avoid the conversion of your saving from Euro into your national currency. In case of EURO CRASH, only the Central Bank will decide what happens to ALL the Euro deposited wherever, single banks, even if they are Deutsche Bank or BNP or ING, can not decide what to do on their own. ECB (European Central Bank) might decide to convert EURO into local currencies based on the account's owner nationality. Therefor if you are Greek and you moved your saving in a German bank, the ECB might decide that your Euro are converted into New Dracma even if they sit in a German bank account. The funniest thing is that if you ask to a Finland bank: \"\"In case of Euro crash, would you convert my Euro into New Dracma?\"\", they sure would answer \"\"No, we can't!\"\", which is true, they can not because it's only the ECB (Europe Central Bank) the one that decides how an ordered Euro crash has to be manged, and the ECB might decide as I explained you above. Other Central Banks (Swiss, FED, etc.) would only follow the decisions of the ECB. Moreover in case of EURO DOOM, it's highly probable that the Euro currency looses a tremendous value compared to other currencies, the loss would be huge in case the Euro Crash happens in a disordered way (i.e. a strong country like Germany and their banks decides to get out and they start printing their own money w/o listening to the ECB anymore). So even if your saving are in Euro in Germany they would loose so much value (compared to other currencies) that you will regreat forever not to have converted them into another currency when you had the time to do it. Couple of advises: 1) If you want to change you savings into another currency you don't need to bring them into another bank/country (like US), you could simply buy US Shares/Bonds at your local bank. Shares/Bonds of a US company/US gov will always be worth their value in dollars no matter in what new pathetic currency your account will be converted. 2) But is there a drawback in converting my saving into another currency (i.e. buying dollars in the form of US treasury bonds)? Unfortunately yes, the drawback is that in case this Euro drama comes finally to an happy ending and Germans decide to open their wallets for the nth time to save the currency, the Euro might suddenly increase its value compared to other currencies, therefor if you changed your saving into another currency you might loose money (i.e. US dollars looses value against the Euro).\"",
"title": ""
},
{
"docid": "340436",
"text": "You bet if it was so simple. This is when financial acumen comes into its true form. The bank would never ever want to go insolvent. What it does is, take insurance against the borrower defaulting. Remember the financial crisis of 2008 which was the outcome of borrowers defaulting. The banks had created derivatives based on the loans distributed. CDO, CDS are some of the simple derivatives banks sell to cover their backs in case of defaults. There are derivatives using these derivatives as underlyings which they then sold it across to other buyers including other banks. Google for Fabrice Tourre and you would realise how much deep the banks go to save themselves from defaulters. If everything fails then go to the government for help. That was what happened when the US government doled out $600 billion to save the financial sector.",
"title": ""
},
{
"docid": "262452",
"text": "I hope there's so much wrong with what I wrote, I do. Thank you for correcting me. For argument's sake, my following responses will assume that you are talking about the US market. Almost any other kind of argument would take too long to elaborate or expand upon. In North America, the rules of Capitalism *are* somewhat ironclad, are they not? Did Americans have a debate over whether or not workers even have the right to strike, or collectively bargain, last year? Aside from that, I am aware hat other US companies do in fact offer much better benefits than others. Target, for example, offers much better healthcare insurance than Walmart does. This is among one of many boons that Target offers to its employees. It can be argued that Target treats its employees much better than Walmart, including its part-time employees. Why, therefore, is Target not much more popular than Walmart? My answer would be that the average consumer does not care about much except lower prices, and those consumers that do, do not shop at Walmart, which is still the most popular supermarket chain in the US. The consumers who do shop at a different or more expensive chain are therefore in the minority, whether because of morals or lack of choice. Corporations are amoral. They exist solely to make a profit, and nothing else. Compassion does not come into it. Higher standards are, and will expand, if there is consumer interest in them doing so. Outsourcing definitely applies here. You've seen the self-checkout facilities available at most stores? When there is a way of scanning every product a person has on them before they exit the store as well as a way of preventing them from exiting the store before they've paid for those goods, you can bet anything on almost every cashier in America being fired from the stores that can afford it. We are very, very close to that, in terms of technology alone, let alone deployment. The US cannot afford to impose tariffs, unfortunately. With every anti-competitive tariff it imposes, exports and imports go down in the billions of dollar ranges. It is not a coincidence that the Eurozone countries who have led the way in tariffs are those you names in your post. In the age of globalisation, everyone can simply go...somewhere else for their needs. The same unfortunately goes for taxes, import premiums, or anything else that you care to name. I agree with you that fighting for labour rights across the world is the only effective answer to that. But that will of course never happen. When labour rights issues erupt in the country that the majority of the world's manufacturing happens, most corporations will simply stick with it until their position becomes untenable, and then they will move to a different country, where labour laws are not as as strong. China is this generation's manufacturing bitch, who will be next? Because companies are worrying about this already.They are looking at shithole places in India, and places in Brazil, and places in Ghana, or Indonesia, or anywhere else that can be persuaded to educate a proportion of its workforce to the minimum necessary levels. It's sad but, remember that if any thought is applied to this, the people who make the things that Chinese/Indian/Ghanan/Indonesian make for pennies on the dollar is that those people's wages will eventually rise enough that there can be a middle-class, at which point the companies involved simply move on to a country that does not have a middle-class or a higher-working class. Forever. That's...the multinational plan. Capitalism, remember, is a system based on unlimited expansion. It just is. No arguing round that one. And finally, 'fiscally sensible' means, to me, that a country retreats from the goddamn cliff it's on when it sees that if it carries on this way, it's truly, amazingly fucked. The debt ceiling fiasco earlier nearly plunged the world economy into recession, in spite of the fact that it should have been a done deal, something nobody anywhere got their tits up about. But no. Politicians literally ransomed it for things that they wanted that were kinda contrary to the interests of the US economy at large, and therefore the fucking WORLD economy at large. If the US had defaulted, it would have fairly literally fucked to rest of us. And I mean the other 670,000,000,000 people alive right now. All coz your Republicans didn't like a black guy. What? Barack Obama does things by pretty classical Keynesian economics. By following those tenets, the whole goddamn world enjoyed a period of uninterrupted growth and prosperity from 1948 to about 1970, depending on where you are. Talk to me all you like about Europe's destroyed industry from WW2 but the simple fact is that the maxim of 'save during booms' and 'spend during busts' created more jobs and helped more economies that you can name. Thanks to political expediency, however, and apparently Reagan, the US at large seems to believe that anything even approaching left-wing politics (and for the purposes of this argument that includes healthcare and, y'know, not caring what or who a woman puts up their vagina) is anathema. It simply isn't accepted, and decried as 'socialism' by any opponents. These arguments and these debates literally don't make any fucking sense to the rest of us. Not even a little bit. Abortion, gay marriage, legalizing marijuana, *NOT* invading other countries. These issues are settled for the vast, vast majority of us. It's fucking insane to us that they aren't for you. In fairness it is, however, because of your politics that you can't do any of these things. You are a nation of three hundred and fifteen million. It can't be expected of you that you have a consensus on these issues. But what gets us is that you never fucking try. We have the European Parliament, imperfect though it may be. It still gives us a voice in issues as basic as gay marriage or abortion. We aren't in permanent deadlock over things as unimportant as this. I don't mean to paint Europe or anywhere else as some kind of paradise. Just that companies in Europe seem to just not care; companies in the US seem to be out to try and actively fuck you. Quick edit: holy shit that was a long reply, don't bother reading it. TL;DR: Companies don't give a shit if they fuck you or not unless market conditions",
"title": ""
},
{
"docid": "593790",
"text": "\"Beyond the yield/price relationship, a good intuitive way to understand it is just this: these people control a substantial amount of money that could be essentially loaned to governments. If they feel a particular policy is likely to lead to inflation or default, they may decide not to loan that country any more money. All else being equal, with a smaller supply of possible borrowers, the country will have to pay higher interest to fund a particular amount of debt. Furthermore they may loudly publicly announce that they will no longer lend to that country, in which case other participants may be persuaded that they too should no longer lend at the going rate. What's more, this is somewhat self-fulfilling: as rates go up, the country will spend more money servicing its debt, and will in fact become a worse risk. So I think the thing that gives them their \"\"vigilante\"\" nature is that governments worry they will round up a posse and things will run away. As far as actual incentives, I would welcome more information but I think the main bond vigilante case is that they are basically long on the country but want it to tighten up its policy so their existing holdings don't decline.\"",
"title": ""
},
{
"docid": "402967",
"text": "Many of the major indices retreated today because of this news. Why? How do the rising budget deficits and debt relate to the stock markets? The major reason for the market retreating is the uncertainty regarding the US Dollar. If the US credit rating drops that will have an inflationary effect on the currency (as it will push up the cost of US Treasuries and reduce confidence in the USD). If this continues the loss of USD confidence could bring an end to the USD as the world's reserve currency which could also create inflation (as world banks could reduce their USD reserves). This can make US assets appear overvalued. Why is there such a large emphasis on the S&P rating? S&P is a large trusted rating agency so the market will respond to their analysis much like how a bank would respond to any change in your rating by Transunion (Consumer Credit Bureau) Does this have any major implications for the US stock markets today, in the short term and in July? If you are a day-trader I'm sure it does. There will be minor fluctuations in the market as soon as news comes out (either of its extension or any expected delays in passing that extension). What happens when the debt ceiling is reached? Since the US is in a deficit spending situation it needs to borrow more to satisfy its existing obligations (in short it pays its debt with more debt). As a result, if the debt ceiling isn't raised then eventually the US will be unable to pay its existing obligations. We would be in a default situation which could have devastating affects on the value of the USD. How hard the hit will depend on how long the default situation lasts (the longer we go without an increased ceiling after the exhaustion point the more we default on). In reality, Congress will approve a raise, but they will drag it out to the last possible minute. They want to appear as if they are against it, but they understand the catastrophic effects of not doing so.",
"title": ""
},
{
"docid": "298794",
"text": "It's more complicated than that. Governments raise money in a number of ways. First, they tax economic activity within their borders and for connected companies and individuals. Then, some governments have actual revenues from state-owned enterprises (licences, patents, courts, business revenues, and so on). Whatever shortage arises between state expenditure and this income is the deficit which is usually financed through debt. Government usually issues a bond (Wikipedia for a list of government bonds) of various types, some with extremely lengthy maturation dates. These bonds can be purchased both locally and by foreign investment funds. The nature of who buys is important. From the Wikipedia link you'll see that most government debt is very highly rated based on the ability of the state to simply raise taxes in order to fund redemption. Pension funds are legally bound to only invest in highly-rated investment classes and the bulk of bonds may be purchased to support local pensioners. A state that defaults on debt will first hit its own most vulnerable citizens. In addition, the fall-out will result in a savage cut in ratings. Countries like Argentina and Zimbabwe, which have both refused to repay their debts even to the IMF, are currently unable to raise investment at all. This has a tremendous impact on local economic development. So, default is out of the question without severe penalties. The second part of your question is about paying down the debt. As debts increase, more and more of the revenue that a country does earn is spent on servicing debt repayments. Sometimes bonds are issued merely to refinance old debt. A country that spends too much on refinancing debt is no different from an individual. Less and less money is available to do other things. In conclusion: governments can neither default nor binge-borrow unless they wish to severely limit economic opportunities for their citizens.",
"title": ""
},
{
"docid": "135128",
"text": "From my limited experience, having taken a class on Bankruptcy in order to become a paralegal, Chapter 11 is the portion of the Bankruptcy Code that allows certain corporate entities to reorganize. Basically, the entity files for bankruptcy protection to halt credit collections or any number of reasons, and then work with the courts to get out. If the entity can put together a reasonable sounding restructuring plan, the court may allow them to do it. A restructuring plan essentially is a plan of who to pay back, when, and by what means (this is seriously a simple explanation, it's much more complex than this). So if the Court approves the plan, the entity will attempt to carry it out and come out of bankruptcy several years down the road in a more solvent position. If the Court rejects the plan or the plan fails, then the entity has to then engage in Chapter 7 proceedings (selling assets to pay off debts).",
"title": ""
},
{
"docid": "162592",
"text": "Using the default values for age and retirement and only making the changes you specified in the question. assumed ROR: 6%, current tax rate: 25%, retirement tax rate: 15%, married, have an employer retirement plan. The results from the two calculators are: Traditional IRA: 631,341 IRA before taxes 536,640 IRA after taxes. Roth IRA: 631,341 Roth IRA 450,207 Taxable Savings where: Total taxable savings The total amount you would have accumulated by retirement in a taxable savings account. your question: The (Traditional) IRA After Taxes value is 6.3% higher than the (Roth) Taxable Savings amount. (Both had an equal gross amount.) Does that mean I should put my money in a tIRA instead of a Roth? My percentages don't match your percentages because you didn't specify the numbers you used. In any case the 450K number shows you what you would have if the money was not invested in an IRA or 401K. To decide between a Roth and a traditional IRA ignore the taxable savings number, that only shows what happens if you decide not not use a retirement account.",
"title": ""
},
{
"docid": "3455",
"text": "As I'm sure you are reading in Hull's classic, the basic valuation of bonds depends on the chance of entity defaulting on those bonds. Let's start with just looking at the US. The United States has a big advantage over corporations in issuing debt as it also prints the same currency that the debt is denominated in. This makes it much easier not to default on your debt as you can always print more money to pay it. Printing too much currency would cause inflation lowering the value of debt, but this would also lower the value of US corporate debt as well. So you can think of even the highest rated corporate bonds as having the same rate as government debt plus a little extra due to the additional default risk of the corporation. The situation with other AA rated governments is more complicated. Most of those governments have debt denominated in their local currency as well so it may seem like they should all have similar rates. However, some governments have higher and some actually have lower rates than the United States. Now, as above, some of the difference is due to the possible need of printing too much currency to cover the debt in crisis and now that we have more than one country to invest in the extra risk of international money flowing out of the country's bonds. However, the bigger difference between AA governments rates depends more on money flow, central banks and regulation. Bonds are still mostly freely traded instruments that respond to supply and demand, but this supply and demand is heavily influenced by governments. Central banks buy up large portions of the debt raising demand and lowering rates. Regulators force banks to hold a certain amount of treasuries perhaps inflating demand. Finally, to answer your question the United States has some interesting advantages partially just due to its long history of stability, controlled inflation and large economy making treasuries valuable as one of the lowest risk investments. So its rates are generally on the low end, but government manipulation can still mean that it is not necessarily the lowest.",
"title": ""
},
{
"docid": "94686",
"text": "\"I am not an expert in this stuff, but my understanding is that the debt is in the form of US treasury securities, which mature at set rates and are paid at maturation. So technically, the US Treasury \"\"pays off\"\" a portion of its debt whenever the debt securities mature. Thus, if China (or any country) buys new Treasury securities at a slower rate than its currently held Treasury securities are maturing, the amount of US debt held by China will decrease. This is what I hear China has been doing recently.\"",
"title": ""
},
{
"docid": "122491",
"text": "\"Great question. There are several reasons; I'm going to list the few that I can think of off the top of my head right now. First, even if institutional bank holdings in such a term account are covered by deposit insurance (this, as well as the amount covered, varies geographically), the amount covered is generally trivial when seen in the context of bank holdings. An individual might have on the order of $1,000 - $10,000 in such an account; for a bank, that's basically chump change, and you are looking more at numbers in the millions of dollars range. Sometimes a lot more than that. For a large bank, even hundreds of millions of dollars might be a relatively small portion of their holdings. The 2011 Goldman Sachs annual report (I just pulled a big bank out of thin air, here; no affiliation with them that I know of) states that as of December 2011, their excess liquidity was 171,581 million US dollars (over 170 billion dollars), with a bottom line total assets of $923,225 million (a shade under a trillion dollars) book value. Good luck finding a bank that will pay you 4% interest on even a fraction of such an amount. GS' income before tax in 2011 was a shade under 6.2 billion dollars; 4% on 170 billion dollars is 6.8 billion dollars. That is, the interest payments at such a rate on their excess liquidity alone would have cost more than they themselves made in the entire year, which is completely unsustainable. Government bonds are as guaranteed as deposit-insurance-covered bank accounts (it'll be the government that steps in and pays the guaranteed amount, quite possibly issuing bonds to cover the cost), but (assuming the country does not default on its debt, which happens from time to time) you will get back the entire amount plus interest. For a deposit-insured bank account of any kind, you are only guaranteed (to the extent that one can guarantee anything) the maximum amount in the country's bank deposit insurance; I believe in most countries, this is at best on the order of $100,000. If the bank where the money is kept goes bankrupt, for holdings on the order of what banks deal with, you would be extremely lucky to recover even a few percent of the principal. Government bonds are also generally accepted as collateral for the bank's own loans, which can make a difference when you need to raise more money in short order because a large customer decided to withdraw a big pile of cash from their account, maybe to buy stocks or bonds themselves. Government bonds are generally liquid. That is, they aren't just issued by the government, held to maturity while paying interest, and then returned (electronically, these days) in return for their face value in cash. Government bonds are bought and sold on the \"\"secondary market\"\" as well, where they are traded in very much the same way as public company stocks. If banks started simply depositing money with each other, all else aside, then what would happen? Keep in mind that the interest rate is basically the price of money. Supply-and-demand would dictate that if you get a huge inflow of capital, you can lower the interest rate paid on that capital. Banks don't pay high interest (and certainly wouldn't do so to each other) because of their intristic good will; they pay high interest because they cannot secure capital funding at lower rates. This is a large reason why the large banks will generally pay much lower interest rates than smaller niche banks; the larger banks are seen as more reliable in the bond market, so are able to get funding more cheaply by issuing bonds. Individuals will often buy bonds for the perceived safety. Depending on how much money you are dealing with (sold a large house recently?) it is quite possible even for individuals to hit the ceiling on deposit insurance, and for any of a number of reasons they might not feel comfortable putting the money in the stock market. Buying government bonds then becomes a relatively attractive option -- you get a slightly lower return than you might be able to get in a high-interest savings account, but you are virtually guaranteed return of the entire principal if the bond is held to maturity. On the other hand, it might not be the case that you will get the entire principal back if the bank paying the high interest gets into financial trouble or even bankruptcy. Some people have personal or systemic objections toward banks, limiting their willingness to deposit large amounts of money with them. And of course in some cases, such as for example retirement savings, it might not even be possible to simply stash the money in a savings account, in which case bonds of some kind is your only option if you want a purely interest-bearing investment.\"",
"title": ""
}
] |
PLAIN-2837
|
Meat Mythcrushers
|
[
{
"docid": "MED-4804",
"text": "BACKGROUND: Alcohol-based hand rubs (ABHRs) are an effective means of decreasing the transmission of bacterial pathogens. Alcohol is not effective against Clostridium difficile spores. We examined the retention of C. difficile spores on the hands of volunteers after ABHR use and the subsequent transfer of these spores through physical contact. METHODS: Nontoxigenic C. difficile spores were spread on the bare palms of 10 volunteers. Use of 3 ABHRs and chlorhexidine soap-and-water washing were compared with plain water rubbing alone for removal of C. difficile spores. Palmar cultures were performed before and after hand decontamination by means of a plate stamping method. Transferability of C. difficile after application of ABHR was tested by having each volunteer shake hands with an uninoculated volunteer. RESULTS: Plain water rubbing reduced palmar culture counts by a mean (+/- standard deviation [SD]) of 1.57 +/- 0.11 log10 colony-forming units (CFU) per cm2, and this value was set as the zero point for the other products. Compared with water washing, chlorhexidine soap washing reduced spore counts by a mean (+/- SD) of 0.89 +/- 0.34 log10 CFU per cm2; among the ABHRs, Isagel accounted for a reduction of 0.11 +/- 0.20 log10 CFU per cm2 (P = .005), Endure for a reduction of 0.37 +/- 0.42 log10 CFU per cm2 (P = .010), and Purell for a reduction of 0.14 +/- 0.33 log10 CFU per cm2 (P = .005). There were no statistically significant differences between the reductions achieved by the ABHRs; only Endure had a reduction statistically different from that for water control rubbing (P = .040). After ABHR use, handshaking transferred a mean of 30% of the residual C. difficile spores to the hands of recipients. CONCLUSIONS: Hand washing with soap and water is significantly more effective at removing C. difficile spores from the hands of volunteers than are ABHRs. Residual spores are readily transferred by a handshake after use of ABHR.",
"title": "Effectiveness of alcohol-based hand rubs for removal of Clostridium difficile spores from hands."
},
{
"docid": "MED-4593",
"text": "AIMS: The objective of the study was to determine the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) contamination of retail meat and to determine the level of contamination. METHODS AND RESULTS: Pork (pork chops and ground pork), ground beef and chicken (legs, wings and thighs) were purchased at retail outlets in four Canadian provinces and tested for the presence of methicillin-resistant Staph. aureus using qualitative and quantitative methods. MRSA was isolated from 9.6% of pork, 5.6% of beef and 1.2% of chicken samples (P = 0.0002). Low levels of MRSA were typically present, with 37% below the detection threshold for quantification and <100 CFU g(-1) present in most quantifiable samples. All isolates were classified as Canadian epidemic MRSA-2 (CMRSA-2) by pulsed field gel electrophoresis (PFGE), with two different PFGE subtypes, and were spa type 24/t242. CONCLUSIONS: MRSA contamination of retail meat is not uncommon. While CMRSA-2, a human epidemic clone, has been found in pigs in Canada, the lack of isolation of livestock-associated ST398 was surprising. SIGNIFICANCE AND IMPACT OF THE STUDY: The relevance of MRSA contamination of meat is unclear but investigation is required because of the potential for exposure from food handling. Sources of contamination require investigation because these results suggest that human or animal sources could be involved.",
"title": "Detection and quantification of methicillin-resistant Staphylococcus aureus (MRSA) clones in retail meat products."
},
{
"docid": "MED-4594",
"text": "Researchers, veterinary and health care practitioners, and agricultural producers gathered in Johnston, Iowa, to attend the eighth annual Midwest Rural Agricultural Safety and Health Forum (MRASH), November 2009. Among several focus areas, four plenary talks were given on the current research being conducted examining methicillin-resistant Staphylococcus aureus (MRSA) on swine farms in the United States. These focused on prevalence of MRSA on farms, both in swine and in human workers; the presence of MRSA in air samples and in swine barn shower facilities; and the presence of methicillin-resistant and methicillin-sensitive S. aureus in retail meats. These findings begin to elucidate the overall picture of livestock-associated MRSA in the Midwestern United States.",
"title": "An overview of livestock-associated MRSA in agriculture."
}
] |
[
{
"docid": "MED-2671",
"text": "Microbiology of meats has been a subject of great concern in food science and public health in recent years. Although many articles have been devoted to the microbiology of beef, pork, and poultry meats, much less has been written about microbiology of lamb meat and even less on restructured lamb meat. This article presents data on microbiology and shelf-life of fresh lamb meat; restructured meat products, restructured lamb meat products, bacteriology of restructured meat products, and important foodborne pathogens such as Salmonella, Escherichia coli O157:H7, and Listeria monocytogenes in meats and lamb meats. Also, the potential use of sodium and potassium lactates to control foodborne pathogens in meats and restructured lamb meat is reviewed This article should be of interest to all meat scientists, food scientists, and public health microbiologists who are concerned with the safety of meats in general and lamb meat in particular.",
"title": "Microbiology of fresh and restructured lamb meat: a review."
},
{
"docid": "MED-5235",
"text": "Several prospective studies have reported that risk of type 2 diabetes (T2DM) is elevated in meat consumers, especially when processed meats are consumed. Elevated risks of coronary heart disease (CHD) and stroke in meat consumers have also been reported. In this overview, the evidence regarding meat consumption and the risk of diabetes, both type 1 diabetes (T1DM) and T2DM and their macro- and microvascular complications, is reviewed. For T2DM, we performed a new meta-analysis including publications up to October 2012. For T1DM, only a few studies have reported increased risks for meat consumers or for high intake of saturated fatty acids and nitrates and nitrites. For T2DM, CHD, and stroke, the evidence is strongest. Per 100 g of total meat, the pooled relative risk (RR) for T2DM is 1.15 (95 % CI 1.07-1.24), for (unprocessed) red meat 1.13 (95 % CI 1.03-1.23), and for poultry 1.04 (95 % CI 0.99-1.33); per 50 g of processed meat, the pooled RR is 1.32 (95 % CI 1.19-1.48). Hence, the strongest association regarding T2DM is observed for processed (red) meat. A similar observation has been made for CHD. For stroke, however, a recent meta-analysis shows moderately elevated risks for meat consumers, for processed as well as for fresh meats. For the microvascular complications of diabetes, few prospective data were available, but suggestions for elevated risks can be derived from findings on hyperglycemia and hypertension. The results are discussed in the light of the typical nutrients and other compounds present in meat--that is, saturated and trans fatty acids, dietary cholesterol, protein and amino acids, heme-iron, sodium, nitrites and nitrosamines, and advanced glycation end products. In light of these findings, a diet moderate to low in red meat, unprocessed and lean, and prepared at moderate temperatures is probably the best choice from the public health point of view.",
"title": "Meat consumption, diabetes, and its complications."
},
{
"docid": "MED-5326",
"text": "The effect of meat consumption on cancer risk is a controversial issue. However, recent meta-analyses show that high consumers of cured meats and red meat are at increased risk of colorectal cancer. This increase is significant but modest (20-30%). Current WCRF-AICR recommendations are to eat no more than 500 g per week of red meat, and to avoid processed meat. Moreover, our studies show that beef meat and cured pork meat promote colon carcinogenesis in rats. The major promoter in meat is heme iron, via N-nitrosation or fat peroxidation. Dietary additives can suppress the toxic effects of heme iron. For instance, promotion of colon carcinogenesis in rats by cooked, nitrite-treated and oxidized high-heme cured meat was suppressed by dietary calcium and by α-tocopherol, and a study in volunteers supported these protective effects in humans. These additives, and others still under study, could provide an acceptable way to prevent colorectal cancer. Copyright © 2011 Elsevier B.V. All rights reserved.",
"title": "Red meat and colon cancer: should we become vegetarians, or can we make meat safer?"
},
{
"docid": "MED-1802",
"text": "Hypotheses regarding the role of meat consumption in body weight modulation are contradictory. Prospective studies on an association between meat consumption and BMI change are limited. We assessed the association between meat consumption and change in BMI over time in 3902 men and women aged 55-69 y from the Netherlands Cohort Study. Dietary intake was estimated at baseline using a FFQ. BMI was ascertained through baseline self-reported height (1986) and weight (1986, 1992, and 2000). Analyses were based on sex-specific categories of daily total fresh meat, red meat, beef, pork, minced meat, chicken, processed meat, and fish consumption at baseline. Linear mixed effect modeling adjusted for confounders was used to assess longitudinal associations. Significant cross-sectional differences in BMI between quintiles of total meat intake were observed (P-trend < 0.01; both sexes). No association between total fresh meat consumption and prospective BMI change was observed in men (BMI change highest vs. lowest quintile after 14 y: -0.06 kg/m²; P = 0.75) and women (BMI change: 0.26 kg/m²; P = 0.20). Men with the highest intake of beef experienced a significantly lower increase in BMI after 6 and 14 y than those with the lowest intake (BMI change after 14 y 0.60 kg/m²). After 14 y, a significantly higher increase in BMI was associated with higher intakes of pork in women (BMI change highest vs. lowest quintile: 0.47 kg/m²) and chicken in both sexes (BMI change highest vs. lowest category in both men and women: 0.36 kg/m²). The results remained similar when stratifying on median baseline BMI, and age-stratified analyses yielded mixed results. Differential BMI change effects were observed for several subtypes of meat. However, total meat consumption, or factors directly related to total meat intake, was not strongly associated with weight change during the 14-y prospective follow-up in this elderly population.",
"title": "Longitudinal changes in BMI in older adults are associated with meat consumption differentially, by type of meat consumed."
},
{
"docid": "MED-4482",
"text": "Consumption of red meat, particularly well done meat, has been associated with increased prostate cancer risk. High temperature cooking methods such as grilling and barbequeing may produce heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) which are known carcinogens. We assessed the association with meat consumption and estimated HCA and PAH exposure in a population-based case-control study of prostate cancer. Newly diagnosed cases aged 40–79 years (531 advanced cases, 195 localized cases) and 527 controls were asked about dietary intake, including usual meat cooking methods and doneness levels. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariate logistic regression. For advanced prostate cancer, but not localized disease, increased risks were associated with higher consumption of hamburgers (OR=1.79. CI=1.10–2.92), processed meat (OR=1.57, CI=1.04, 2.36), grilled red meat (OR=1.63, CI=0.99–2.68), and well done red meat (OR=1.52, CI=0.93–2.46), and intermediate intake of 2-amino-1-methyl1-6-phenylimidazo[4,5-b]pyridine (PhIP) (quartile 2 vs. 1: OR=1.41, CI=0.98–2.01; quartile 3 vs. 1: OR=1.42, CI=0.98–2.04), but not for higher intake. White meat consumption was not associated with prostate cancer. These findings provide further evidence that consumption of processed meat and red meat cooked at high temperature is associated with increased risk of advanced, but not localized prostate cancer.",
"title": "Meat consumption, Cooking Practices, Meat Mutagens and Risk of Prostate Cancer"
},
{
"docid": "MED-4057",
"text": "BACKGROUND: Heterocyclic amines, mutagens formed in meats cooked at high temperatures, have been demonstrated as mammary carcinogens in animals. We conducted a nested, case-control study among 41836 cohort members of the Iowa Women's Health Study to evaluate the potential role of heterocyclic amines and intake of well-done meat in the risk for human breast cancer. METHODS: A questionnaire was mailed to individuals in the cohort who had breast cancer diagnosed during the period from 1992 through 1994 and a random sample of cancer-free cohort members to obtain information on usual intake of meats and on meat preparation practices. Color photographs showing various doneness levels of hamburger, beefsteak, and bacon were included. Multivariate analysis was performed on data from 273 case subjects and 657 control subjects who completed the survey. RESULTS: A dose-response relationship was found between doneness levels of meat consumed and breast cancer risk. The adjusted odds ratios (ORs) for very well-done meat versus rare or medium-done meat were 1.54 (95% confidence interval [CI]=0.96-2.47) for hamburger, 2.21 (95% CI=1.30-3.77) for beef steak, and 1.64 (95% CI=0.92-2.93) for bacon. Women who consumed these three meats consistently very well done had a 4.62 times higher risk (95% CI=1.36-15.70) than that of women who consumed the meats rare or medium done. Risk of breast cancer was also elevated with increasing intake of well-done to very well-done meat. CONCLUSIONS: Consumption of well-done meats and, thus, exposures to heterocyclic amines (or other compounds) formed during high-temperature cooking may play an important role in the risk of breast cancer.",
"title": "Well-done meat intake and the risk of breast cancer."
},
{
"docid": "MED-2170",
"text": "Background/Aim Harmane [1-methyl-9H-pyrido(3,4-b)indole] is a tremor-producing neurotoxin. Blood harmane concentrations are elevated in essential tremor (ET) patients for unclear reasons. Potential mechanisms include increased dietary harmane intake (especially through well-cooked meat) or genetic-metabolic factors. We tested the hypothesis that meat consumption and level of meat doneness are higher in ET cases than in controls. Methods Detailed data were collected using the Lawrence Livermore National Laboratory Meat Questionnaire. Results Total current meat consumption was greater in men with than without ET (135.3 ± 71.1 vs. 110.6 ± 80.4 g/day, p = 0.03) but not in women with versus without ET (80.6 ± 50.0 vs. 79.3 ± 51.0 g/day, p = 0.76). In an adjusted logistic regression analysis in males, higher total current meat consumption was associated with ET (OR = 1.006, p = 0.04, i.e., with 10 additional g/day of meat, odds of ET increased by 6%). Male cases had higher odds of being in the highest than lowest quartile of total current meat consumption (adjusted OR = 21.36, p = 0.001). Meat doneness level was similar in cases and controls. Conclusion This study provides evidence of a dietary difference between male ET cases and male controls. The etiological ramifications of these results warrant additional investigation. Copyright © 2008 S. Karger AG, Basel",
"title": "Dietary Epidemiology of Essential Tremor: Meat Consumption and Meat Cooking Practices"
},
{
"docid": "MED-4977",
"text": "Background/Aim Harmane [1-methyl-9H-pyrido(3,4-b)indole] is a tremor-producing neurotoxin. Blood harmane concentrations are elevated in essential tremor (ET) patients for unclear reasons. Potential mechanisms include increased dietary harmane intake (especially through well-cooked meat) or genetic-metabolic factors. We tested the hypothesis that meat consumption and level of meat doneness are higher in ET cases than in controls. Methods Detailed data were collected using the Lawrence Livermore National Laboratory Meat Questionnaire. Results Total current meat consumption was greater in men with than without ET (135.3 ± 71.1 vs. 110.6 ± 80.4 g/day, p = 0.03) but not in women with versus without ET (80.6 ± 50.0 vs. 79.3 ± 51.0 g/day, p = 0.76). In an adjusted logistic regression analysis in males, higher total current meat consumption was associated with ET (OR = 1.006, p = 0.04, i.e., with 10 additional g/day of meat, odds of ET increased by 6%). Male cases had higher odds of being in the highest than lowest quartile of total current meat consumption (adjusted OR = 21.36, p = 0.001). Meat doneness level was similar in cases and controls. Conclusion This study provides evidence of a dietary difference between male ET cases and male controls. The etiological ramifications of these results warrant additional investigation. Copyright © 2008 S. Karger AG, Basel",
"title": "Dietary Epidemiology of Essential Tremor: Meat Consumption and Meat Cooking Practices"
},
{
"docid": "MED-4175",
"text": "In this study, 10 perfluorochemicals (PFCs) were measured in meat, meat products, and eggs, and in indoor dust, collected in China. Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) were the most frequently detected PFCs in these samples. Mean concentrations of PFOS and PFOA in foodstuffs were in the range of 0.05-1.99 ng/g fresh wt and 0.06-12.5 ng/g fresh wt, respectively. The mean concentrations of PFOA, perfluoroheptanoic acid (PFHpA), and PFOS in indoor dust were 205, 14.0, and 4.86 ng/g, dry wt, respectively. The estimated daily intake of PFOS and PFOA from meat, meat products and eggs (EDI(meat&eggs)) ranged from 6.00 to 9.64 ng/d and from 254 to 576 ng/d, respectively, when the values below the limit of quantitation (LOQ) were assigned as 0, and from 8.80 to 15.0 ng/d and from 255 to 577 ng/d, respectively, when the values below the LOQ were set at 1/2LOQ. The EDI(meat&eggs) of PFOS and PFOA increased with increasing family income. The estimated daily intake of PFOS and PFOA through inhalation of dust (EDI(dust)) ranged from 0.23 to 0.31 ng/d and from 9.68 to 13.4 ng/d, respectively. The daily intakes of PFOS and PFOA from the consumption of meat, meat products, and eggs, and from dust ingestion, as calculated from our samples in this study, were compared with estimated daily intake of PFCs reported from the concentrations in drinking water, fish and seafood from China. Our calculations indicate that dietary sources (EDI(dietary)) account for the overwhelming proportion of (>99% for PFOS and 98% for PFOA) total daily intake (TDI) in adults. The analyzed foodstuffs (meat, meat products, and eggs) were not the major contributors to dietary exposure to PFOS, whereas, meat was the primary contributor to dietary exposure to PFOA.",
"title": "Perfluorochemicals in meat, eggs and indoor dust in China: assessment of sources and pathways of human exposure to perfluorochemicals."
},
{
"docid": "MED-4261",
"text": "BACKGROUND: Meat intake may be related to weight gain because of its high energy and fat content. Some observational studies have shown that meat consumption is positively associated with weight gain, but intervention studies have shown mixed results. OBJECTIVE: Our objective was to assess the association between consumption of total meat, red meat, poultry, and processed meat and weight gain after 5 y of follow-up, on average, in the large European population who participated in the European Prospective Investigation into Cancer and Nutrition-Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating Out of Home and Obesity (EPIC-PANACEA) project. DESIGN: A total of 103,455 men and 270,348 women aged 25-70 y were recruited between 1992 and 2000 in 10 European countries. Diet was assessed at baseline with the use of country-specific validated questionnaires. A dietary calibration study was conducted in a representative subsample of the cohort. Weight and height were measured at baseline and self-reported at follow-up in most centers. Associations between energy from meat (kcal/d) and annual weight change (g/y) were assessed with the use of linear mixed models, controlled for age, sex, total energy intake, physical activity, dietary patterns, and other potential confounders. RESULTS: Total meat consumption was positively associated with weight gain in men and women, in normal-weight and overweight subjects, and in smokers and nonsmokers. With adjustment for estimated energy intake, an increase in meat intake of 250 g/d (eg, one steak at approximately 450 kcal) would lead to a 2-kg higher weight gain after 5 y (95% CI: 1.5, 2.7 kg). Positive associations were observed for red meat, poultry, and processed meat. CONCLUSION: Our results suggest that a decrease in meat consumption may improve weight management.",
"title": "Meat consumption and prospective weight change in participants of the EPIC-PANACEA study."
},
{
"docid": "MED-4485",
"text": "Background Meat could be involved in bladder carcinogenesis via multiple potentially carcinogenic meat-related compounds related to cooking and processing, including nitrate, nitrite, heterocyclic amines (HCAs), and polycyclic aromatic hydrocarbons. We comprehensively investigated the association between meat and meat components and bladder cancer. Methods During 7 years of follow-up, 854 transitional cell bladder cancer cases were identified among 300,933 men and women who completed a validated food frequency questionnaire in the large prospective NIH-AARP Diet and Health Study. We estimated intake of nitrate and nitrite from processed meat and HCAs and PAHs from cooked meat using quantitative databases of measured values. We calculated total dietary nitrate and nitrite based on literature values. Results The hazard ratios (HR) and 95% confidence intervals (CI) for red meat (HR for fifth compared to first quintile=1.22, 95% CI=0.96–1.54, p-trend=0.07) and the HCA 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) (HR=1.19, 95% CI=0.95–1.48, p-trend=0.06) conferred a borderline statistically significant increased risk of bladder cancer. We observed positive associations in the top quintile for total dietary nitrite (HR=1.28, 95% CI=1.02–1.61, p-trend= 0.06) and nitrate plus nitrite intake from processed meat (HR=1.29 95% CI=1.00–1.67, p-trend= 0.11). Conclusions These findings provide modest support for a role for total dietary nitrite and nitrate plus nitrite from processed meat in bladder cancer. Our results also suggest a positive association between red meat and PhIP and bladder carcinogenesis.",
"title": "Meat and components of meat and the risk of bladder cancer in the NIH-AARP Diet and Health Study"
},
{
"docid": "MED-4493",
"text": "Processed meat intake may be involved in the etiology of colorectal cancer, a major cause of death in affluent countries. The epidemiologic studies published to date conclude that the excess risk in the highest category of processed meat-eaters is comprised between 20 and 50% compared with non-eaters. In addition, the excess risk per gram of intake is clearly higher than that of fresh red meat. Several hypotheses, which are mainly based on studies carried out on red meat, may explain why processed meat intake is linked to cancer risk. Those that have been tested experimentally are (i) that high-fat diets could promote carcinogenesis via insulin resistance or fecal bile acids; (ii) that cooking meat at a high temperature forms carcinogenic heterocyclic amines and polycyclic aromatic hydrocarbons; (iii) that carcinogenic N-nitroso compounds are formed in meat and endogenously; (iv) that heme iron in red meat can promote carcinogenesis because it increases cell proliferation in the mucosa, through lipoperoxidation and/or cytotoxicity of fecal water. Nitrosation might increase the toxicity of heme in cured products. Solving this puzzle is a challenge that would permit to reduce cancer load by changing the processes rather than by banning processed meat.",
"title": "Processed meat and colorectal cancer: a review of epidemiologic and experimental evidence"
},
{
"docid": "MED-4758",
"text": "AIM: To examine the relation between meat intake and diabetes occurrence in adults. METHODS: In a prospective cohort study we examined the relation between diet and incident diabetes recorded among 8,401 cohort members (ages 45-88 years) of the Adventist Mortality Study and Adventist Health Study (California, USA) who were non-diabetic at baseline. During the 17-year follow-up, we identified 543 incident diabetes cases. RESULTS: (1) Subjects who were weekly consumers of all meats were 29% (OR = 1.29; 95% CI 1.08, 1.55) more likely (relative to zero meat intake) to develop diabetes. (2) Subjects who consumed any processed meats (salted fish and frankfurters) were 38% (OR = 1.38; 95% CI 1.05-1.82) more likely to develop diabetes. (3) Long-term adherence (over a 17-year interval) to a diet that included at least weekly meat intake was associated with a 74% increase (OR = 1.74; 95% CI 1.36-2.22) in odds of diabetes relative to long-term adherence to a vegetarian diet (zero meat intake). Further analyses indicated that some of this risk may be attributable to obesity and/or weight gain--both of which were strong risk factors in this cohort. It is noteworthy that even after control for weight and weight change, weekly meat intake remained an important risk factor (OR = 1.38; 95% CI 1.06-1.68) for diabetes [corrected]. CONCLUSIONS: Our findings raise the possibility that meat intake, particularly processed meats, is a dietary risk factor for diabetes. 2008 S. Karger AG, Basel.",
"title": "Meats, processed meats, obesity, weight gain and occurrence of diabetes among adults: findings from Adventist Health Studies."
},
{
"docid": "MED-2584",
"text": "In a 6-year prospective study, the authors examined the relation between diet and incident colon cancer among 32,051 non-Hispanic white cohort members of the Adventist Health Study (California, 1976-1982) who, at baseline, had no documented or reported history of cancer. The risk of colon cancer was determined from proportional hazards regression with adjustment for age and other covariates. The authors found a positive association with total meat intake (risk ratio (RR) for > or =1 time/week vs. no meat intake = 1.85, 95% confidence interval (CI) 1.19-2.87; p for trend = 0.01) and, among subjects who favored specific types of meat, positive associations with red meat intake (RR for > or =1 time/week vs. no red meat intake = 1.90, 95% CI 1.16-3.11; p for trend = 0.02) and white meat intake (RR for > or =1 time/week vs. no white meat intake = 3.29, 95% CI 1.60-6.75; p for trend = 0.006). An inverse association with legume intake (RR for >2 times/week vs. <1 time/week = 0.53, 95% CI 0.33-0.86; p for trend = 0.03) was observed. Among men, a positive association with body mass index was observed (relative to the RR for tertile III (>25.6 kg/m2) vs. tertile I (<22.5 kg/m2) = 2.63, 95% CI 1.12-6.13; p for trend = 0.05). A complex relation was identified whereby subjects exhibiting a high red meat intake, a low legume intake, and a high body mass experienced a more than threefold elevation in risk relative to all other patterns based on these variables. This pattern of putative risk factors would likely contribute to increases in both insulin resistance (high body mass, high red meat intake) and glycemic load (low legume intake), a synergism that, if causal, implicates hyperinsulinemic exposure in colon carcinogenesis. The overall findings from this cohort identify both red meat intake and white meat intake as important dietary risk factors for colon cancer and raise the possibility that the risk due to red meat intake reflects a more complex etiology.",
"title": "Dietary risk factors for colon cancer in a low-risk population."
},
{
"docid": "MED-5195",
"text": "We performed a survival analysis to assess the effect of meat consumption and meat type on the risk of breast cancer in the UK Women's Cohort Study. Between 1995 and 1998 a cohort of 35 372 women was recruited, aged between 35 and 69 years with a wide range of dietary intakes, assessed by a 217-item food frequency questionnaire. Hazard ratios (HRs) were estimated using Cox regression adjusted for known confounders. High consumption of total meat compared with none was associated with premenopausal breast cancer, HR=1.20 (95% CI: 0.86–1.68), and high non-processed meat intake compared with none, HR=1.20 (95% CI: 0.86–1.68). Larger effect sizes were found in postmenopausal women for all meat types, with significant associations with total, processed and red meat consumption. Processed meat showed the strongest HR=1.64 (95% CI: 1.14–2.37) for high consumption compared with none. Women, both pre- and postmenopausal, who consumed the most meat had the highest risk of breast cancer.",
"title": "Meat consumption and risk of breast cancer in the UK Women's Cohort Study"
},
{
"docid": "MED-4494",
"text": "Background: Fifty percent of American Indians (AIs) develop diabetes by age 55 y. Whether processed meat is associated with the risk of diabetes in AIs, a rural population with a high intake of processed meat (eg, canned meats in general, referred to as “spam”) and a high rate of diabetes, is unknown. Objective: We examined the associations of usual intake of processed meat with incident diabetes in AIs. Design: This prospective cohort study included AI participants from the Strong Heart Family Study who were free of diabetes and cardiovascular disease at baseline and who participated in a 5-y follow-up examination (n = 2001). Dietary intake was ascertained by using a Block food-frequency questionnaire at baseline. Incident diabetes was defined on the basis of 2003 American Diabetes Association criteria. Generalized estimating equations were used to examine the associations of dietary intake with incident diabetes. Results: We identified 243 incident cases of diabetes. In a comparison of upper and lower quartiles, intake of processed meat was associated with a higher risk of incident diabetes (OR: 1.63; 95% CI: 1.21, 2.63), after adjustment for potential confounders. The relation was particularly strong for spam (OR for the comparison of upper and lower quartiles: 2.06; 95% CI: 1.30, 3.27). Intake of unprocessed red meat was not associated with incident diabetes (OR for the comparison of upper and lower quartiles: 0.90; 95% CI: 0.59, 1.37). Conclusion: The consumption of processed meat, such as spam, but not unprocessed red meat, was associated with higher risk of diabetes in AIs, a rural population at high risk of diabetes and with limited access to healthy foods.",
"title": "Associations of processed meat and unprocessed red meat intake with incident diabetes: the Strong Heart Family Study"
},
{
"docid": "MED-1114",
"text": "Several studies have suggested an increased risk of lymphoma among workers exposed to meat, without conclusive evidence. We conducted a multicenter case-control study during 1998-2004 in the Czech Republic, France, Germany, Ireland, Italy and Spain, including 2,007 cases of non-Hodgkin lymphoma, 339 cases of Hodgkin lymphoma and 2,462 controls. We collected detailed information on occupational history and assessed exposure to meat in general and several types of meat via expert assessment of the questionnaires. The odds ratio (OR) of non-Hodgkin lymphoma for ever occupational exposure to meat was 1.18 (95% confidence interval [CI] 0.95-1.46), that for exposure to beef meat was 1.22 (95% CI 0.90-1.67), and that for exposure to chicken meat was 1.19 (95% CI 0.91-1.55). The ORs were higher among workers with longer duration of exposure. An increased risk among workers exposed to beef meat was mainly apparent for diffuse large B-cell lymphoma (OR 1.49, 95%CI 0.96-2.33), chronic lymphocytic leukemia (OR 1.35, 95% CI 0.78-2.34) and multiple myeloma (OR 1.40, 95%CI 0.67-2.94). The latter 2 types were also associated with exposure to chicken meat (OR 1.55, 95% CI 1.01-2.37, and OR 2.05, 95%CI 1.14-3.69). Follicular lymphoma and T-cell lymphoma, as well as Hodgkin lymphoma did not show any increase in risk. Occupational exposure to meat does not appear to represent an important risk factor of lymphoma, although an increased risk of specific types of non-Hodgkin lymphoma cannot be excluded. (c) 2007 Wiley-Liss, Inc.",
"title": "Occupational exposure to meat and risk of lymphoma: a multicenter case-control study from Europe."
},
{
"docid": "MED-4072",
"text": "It was the aim of this study to examine the association of the consumption of meat in general, meat prepared by different cooking methods and the dietary intake of heterocyclic aromatic amines (HCA) with the level of DNA adducts in the breast tissue of women undergoing reduction mammoplasty. Dietary intake of meat and HCA were assessed via questionnaire in 44 women undergoing reduction mammoplasty. DNA adduct analysis in breast tissue was performed by (32)P-postlabelling analysis. Spearman rank correlation coefficients (r) were calculated to examine the association of meat consumption and dietary HCA intake with tissue DNA adduct levels. A median DNA adduct level of 18.45 (interquartile range 12.81-25.65) per 10(9) nucleotides in breast tissue was observed; median HCA intake was 40.43 ng/day (interquartile range 19.55-102.33 ng/day). Total HCA intake (r = 0.33, P = 0.03), consumption of fried meat (r = 0.39, P = 0.01), beef (r = 0.32, P = 0.03) and processed meat (r = 0.51, P = 0.0004) were statistically significantly correlated with the level of DNA adducts in breast tissue. The detected DNA adducts could not be confirmed to be specific HCA-derived DNA adducts by comparison with external standards, using the (32)P-postlabelling assay. We observed strong correlations of dietary HCA intake and consumption of fried and processed meat with DNA adduct levels in breast tissue of 44 women. Since the detected DNA adducts were not necessarily specific only for HCA, it is possible that HCA intake is a surrogate of other genotoxic substances, such as polycyclic aromatic hydrocarbons, in meat prepared at high temperatures.",
"title": "Dietary intake of meat and meat-derived heterocyclic aromatic amines and their correlation with DNA adducts in female breast tissue."
},
{
"docid": "MED-4382",
"text": "BACKGROUND: Age-related cataract is a major cause of morbidity. Previous studies of diet and cataract risk have focused on specific nutrients or healthy eating indexes but not on identifiable dietary groups such as vegetarians. OBJECTIVE: We investigated the association between diet and cataract risk in a population that has a wide range of diets and includes a high proportion of vegetarians. DESIGN: We used Cox proportional hazards regression to study cataract risk in relation to baseline dietary and lifestyle characteristics of 27,670 self-reported nondiabetic participants aged ≥40 y at recruitment in the Oxford (United Kingdom) arm of the European Prospective Investigation into Cancer and Nutrition (EPIC-Oxford) by using data from the Hospital Episode Statistics in England and Scottish Morbidity Records. RESULTS: There was a strong relation between cataract risk and diet group, with a progressive decrease in risk of cataract in high meat eaters to low meat eaters, fish eaters (participants who ate fish but not meat), vegetarians, and vegans. After multivariable adjustment, incidence rate ratios (95% CIs) for moderate meat eaters (50-99 g meat/d), low meat eaters (<50 g meat/d), fish eaters, vegetarians, and vegans compared with high-meat eaters (≥100 g meat/d) were 0.96 (0.84, 1.11), 0.85 (0.72, 0.99), 0.79 (0.65, 0.97), 0.70 (0.58, 0.84), and 0.60 (0.38, 0.96), respectively (P < 0.001 for heterogeneity). Associations between cataract risk and intakes of selected nutrients and foods generally reflected the strong association with diet group. CONCLUSION: Vegetarians were at lower risk of cataract than were meat eaters in this cohort of health-conscious British residents.",
"title": "Diet, vegetarianism, and cataract risk."
},
{
"docid": "MED-5236",
"text": "AIMS/HYPOTHESIS: A diet rich in meat has been reported to contribute to the risk of type 2 diabetes. The present study aims to investigate the association between meat consumption and incident type 2 diabetes in the EPIC-InterAct study, a large prospective case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. METHODS: During 11.7 years of follow-up, 12,403 incident cases of type 2 diabetes were identified among 340,234 adults from eight European countries. A centre-stratified random subsample of 16,835 individuals was selected in order to perform a case-cohort design. Prentice-weighted Cox regression analyses were used to estimate HR and 95% CI for incident diabetes according to meat consumption. RESULTS: Overall, multivariate analyses showed significant positive associations with incident type 2 diabetes for increasing consumption of total meat (50 g increments: HR 1.08; 95% CI 1.05, 1.12), red meat (HR 1.08; 95% CI 1.03, 1.13) and processed meat (HR 1.12; 95% CI 1.05, 1.19), and a borderline positive association with meat iron intake. Effect modifications by sex and class of BMI were observed. In men, the results of the overall analyses were confirmed. In women, the association with total and red meat persisted, although attenuated, while an association with poultry consumption also emerged (HR 1.20; 95% CI 1.07, 1.34). These associations were not evident among obese participants. CONCLUSIONS/INTERPRETATION: This prospective study confirms a positive association between high consumption of total and red meat and incident type 2 diabetes in a large cohort of European adults.",
"title": "Association between dietary meat consumption and incident type 2 diabetes: the EPIC-InterAct study."
},
{
"docid": "MED-3499",
"text": "Carrageenans are sulfated linear polysaccharides of D-galactose and 3,6-anhydro-D-galactose extracted from red seaweeds. They have been used by the food industry for their gelling, thickening, and stabilizing properties, and more recently by the meat industry for reduced fat products. Meat is a complex system of muscle tissue, connective tissue, fat, and water; during processing, numerous interactions occur among all these components. These interactions are responsible for the functional properties of the meat system. In meat products, carrageenans contribute to gel formation and water retention. Their addition is of special interest in low-fat meat products because fat reduction often leads to unacceptable, tough textures. When carrageenans are incorporated in these formulations, they improve the textural characteristics of the product by decreasing toughness and increasing juiciness. Although carrageenan interactions with milk proteins have been studied extensively, the mechanism by which carrageenans interact with meat proteins and the other meat components is not fully understood.",
"title": "Carrageenans and their use in meat products."
},
{
"docid": "MED-5188",
"text": "BACKGROUND: Nitrosamines, which are known bladder carcinogens, or their precursors are found in certain meat items, and concentrations of these compounds are especially high in bacon. Only 3 cohort studies, all with <100 case subjects, have examined the relation between meat intake and bladder cancer, and few studies have examined the relation of different meat types with bladder cancer. OBJECTIVE: The aim was to examine the association between specific meat items and bladder cancer in 2 large prospective studies. DESIGN: We analyzed data from 2 cohorts with up to 22 y of follow-up and 808 incident bladder cancer cases. Detailed data on meat were obtained from multiple food-frequency questionnaires administered over time. Multivariate relative risks (RRs) and 95% CIs were estimated by using Cox proportional hazards models with control for potential confounders, including detailed smoking history. RESULTS: Men and women with a high intake of bacon (>/=5 servings/wk) had an elevated risk of bladder cancer compared with those who never ate bacon (multivariate RR = 1.59; 95% CI = 1.06, 2.37), although the overall association was not statistically significant (P for trend = 0.06). However, the association with bacon was stronger and became statistically significant after the removal of individuals who indicated having \"greatly\" changed their red meat (men) or bacon (women) intake during the 10 y before baseline (multivariate RR = 2.10; 95% CI = 1.24, 3.55; P for trend = 0.006). A positive association was also detected for intake of chicken without skin, but not for chicken with skin or for other meats, including processed meats, hot dogs, and hamburgers. CONCLUSIONS: In these 2 cohorts combined, frequent consumption of bacon was associated with an elevated risk of bladder cancer. Other studies with data on specific meat items are necessary to confirm our findings.",
"title": "Meat intake and bladder cancer risk in 2 prospective cohort studies."
},
{
"docid": "MED-4814",
"text": "A correlation between national pig-meat consumption and mortality rates from chronic liver disease (CLD) across developed countries was reported in 1985. One possible mechanism explaining this may be hepatitis E infection spread via pig meat. We aimed to re-examine the original association in more recent international data. Regression models were used to estimate associations between national pig-meat consumption and CLD mortality, adjusting for confounders. Data on CLD mortality, alcohol consumption, hepatitis B virus (HBV) and hepatitis C virus (HCV) seroprevalence for 18 developed countries (1990-2000) were obtained from WHO databases. Data on national pig-meat and beef consumption were obtained from the UN database. Univariate regression showed that alcohol and pig-meat consumption were associated with mortality from CLD, but beef consumption, HBV and HCV seroprevalence were not. A 1 litre per capita increase in alcohol consumption was associated with an increase in mortality from CLD in excess of 1.6 deaths/100,000 population. A 10 kg higher national annual average per capita consumption of pork meat was associated with an increase in mortality from CLD of between 4 and 5 deaths/100,000 population. Multivariate regression showed that alcohol, pig-meat consumption and HBV seroprevalence were independently associated with mortality from CLD, but HCV seroprevalence was not. Pig-meat consumption remained independently associated with mortality from CLD in developed countries in the 1990-2000 period. Further work is needed to establish the mechanism.",
"title": "National mortality rates from chronic liver disease and consumption of alcohol and pig meat."
},
{
"docid": "MED-5205",
"text": "Since meat may be involved in the etiology of colorectal cancer, associations between meat-related compounds were examined to elucidate underlying mechanisms in a population-based case-control study. Participants (989 cases/1,033 healthy controls) completed a food frequency questionnaire with a meat-specific module. Multivariable logistic regression was used to examine associations between meat variables and colorectal cancer; polytomous logistic regression was used for subsite-specific analyses. The following significant positive associations were observed for meat-related compounds: 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and colorectal, distal colon, and rectal tumors; 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and colorectal and colon cancer tumors; nitrites/nitrates and proximal colon cancer; 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and rectal cancer; and benzo[a]pyrene and rectal cancer (P-trends < 0.05 ). For analyses by meat type, cooking method, and doneness preference, positive associations between red processed meat and proximal colon cancer and pan-fried red meat and colorectal cancer were found (P-trends < 0.05). Inverse associations were observed between unprocessed poultry and colorectal, colon, proximal colon, and rectal tumors; grilled/barbequed poultry and proximal colon cancer; and well-done/charred poultry and colorectal, colon, and proximal colon tumors (P-trends < 0.05). HCAs, PAHs, nitrites, and nitrates may be involved in colorectal cancer etiology. Further examination into the unexpected inverse associations between poultry and colorectal cancer is warranted.",
"title": "Meat-Related Compounds and Colorectal Cancer Risk by Anatomical Subsite"
},
{
"docid": "MED-4486",
"text": "Diet plays an important role in the etiology of certain cancers, but there is limited evidence with regard to the association between diet and risk of endometrial cancer. Few prospective studies have investigated meat intake as a potential determinant of endometrial cancer risk. The objective of this study was to examine the association between endometrial cancer risk and total meat, red meat, processed meat, fish, and poultry intake. We conducted a case-cohort analysis within the Canadian Study of Diet, Lifestyle, and Health, a prospective cohort of 73 909 adults (39 614 women). Participants were recruited from 1992 to 1999, predominantly from three Canadian universities. We conducted a linkage with the Ontario Cancer Registry for the years 1992-2007 for the female cohort members, who resided in Ontario at the time of enrollment (n=26 024), to yield data on cancer incidence. The analytic sample was comprised of 107 incident cases and 1830 subcohort members, the latter being an age-stratified sample of the full cohort. A nonsignificant increase in the risk of endometrial cancer was associated with increased consumption of red meat [hazard ratio (HR)=1.62, 95% confidence intervals (CI)=0.86-3.08, for high vs. low intake; P trend=0.13)], processed meat (HR=1.45, 95% CI=0.80-2.61, for high vs. low intake; P trend=0.058), and all meat combined (HR=1.50, 95% CI=0.78-2.89, for high vs. low intake; P trend=0.14). No clear patterns were noted for poultry or fish. The results of this study, although based on a limited number of cases, suggest that relatively high meat intake may be associated with increased risk of endometrial cancer.",
"title": "Endometrial cancer and meat consumption: a case-cohort study."
},
{
"docid": "MED-5181",
"text": "Recent evidence suggests overall dietary patterns, rather than specific dietary components, may be a better predictor of colorectal adenomas or cancers. Using cluster analysis, we aimed to assess the association between dietary patterns and colorectal adenomas and whether adjusting for total energy consumption prior to creating clusters affects this relation. Data from a case-control study of 725 individuals undergoing a colonoscopy were utilized. Cases (n = 203) had > or =1 adenoma on colonoscopy, and controls (n = 522) were those who had no adenomas. Dietary data were obtained from an FFQ. Daily intake for 18 different food groups was calculated. The values were transformed into Z-scores. Participants were first clustered without energy adjustment, then again based on their consumption per 1000 kcal (4187 kJ). There was no association between dietary patterns and colorectal adenomas without energy adjustment prior to creating dietary clusters, as clusters formed as a by-product of energy consumption. After adjusting for energy consumption, 3 distinct clusters emerged: 1) high fruit-low meat cluster; 2) high vegetable-moderate meat cluster; and 3) high meat cluster. After adjusting for potential confounders, the high vegetable-moderate meat cluster (odds ratio [OR] 2.17: [95% CI] 1.20-3.90) and high meat cluster (OR 1.70: [95% CI] 1.04-2.80) were at significantly increased odds of having had an adenoma compared with the high fruit-low meat cluster. A high-fruit, low-meat diet appears to be protective against colorectal adenomas compared with a dietary pattern of increased vegetable and meat consumption.",
"title": "A diet high in fruits and low in meats reduces the risk of colorectal adenomas."
},
{
"docid": "MED-2168",
"text": "Harmane, one of the heterocyclic amines (HCAs), is a potent neurotoxin linked to human diseases. Dietary exposure, especially in cooked meats, is the major source of exogenous exposure for humans. However, knowledge of harmane concentrations in cooked meat samples is limited. Our goals were to (1) quantify the concentration of harmane in different types of cooked meat samples, (2) compare its concentration to that of other more well-understood HCAs, and (3) examine the relationship between harmane concentration and level of doneness. Thirty barbecued/grilled meat samples (8 beef steak, 12 hamburger, 10 chicken) were analyzed for harmane and four other HCAs (2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine [PhIP], amino-3,8-dimethylimidazo[4,5-f]quinoxaline [MeIQx], 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline [DiMeIQx], and 2-amino-1,6-dimethylfuro[3,2-e]imidazo[4,5-b]pyridine [IFP]). Mean (+/- SD) harmane concentration was 5.63 (+/- 6.63) ng/g; harmane concentration was highest in chicken (8.48 +/- 9.86 ng/g) and lowest in beef steak (3.80 +/- 3.6 ng/g). Harmane concentration was higher than that of the other HCAs and significantly correlated with PhIP concentration. Harmane concentration was associated with meat doneness in samples of cooked beef steak and hamburger, although the correlation between meat doneness and concentration was greater for PhIP than for harmane. Evidence indicates that harmane was detectable in nanograms per gram quantities in cooked meat (especially chicken) and, moreover, was more abundant than other HCAs. There was some correlation between meat doneness and harmane concentration, although this correlation was less robust than that observed for PhIP. Data such as these may be used to improve estimation of human dietary exposure to this neurotoxin.",
"title": "Quantification of the neurotoxic beta-carboline harmane in barbecued/grilled meat samples and correlation with level of doneness."
},
{
"docid": "MED-2673",
"text": "Transglutaminase is an enzyme that can be used to cross-link pieces of meat, fish or meat products. The resulting product gives the optical impression of an intact chunk of meat. The usage of transglutaminase as a food additive is permitted in some countries. However, its utilisation has to be declared to ensure transparency for consumers. This paper describes two orthogonal analytical methods suited for the detection of technological relevant transglutaminase concentrations (around 25 mg pure enzyme in 1 kg of product) in meat and meat products. The mass spectrometry-based approach relies on a previous digestion with Achromobacter lyticus protease and LC-MS/MS separation and detection. Sufficient selectivity was obtained by monitoring four different peptides. The orthogonal (complementary and independent), ELISA-based approach relies on two commercially available bacterial transglutaminase-specific antibodies, combined to a sandwich ELISA. The two methods were tested by analysing some 60 samples obtained from the market.",
"title": "Determination of microbial transglutaminase in meat and meat products."
},
{
"docid": "MED-4983",
"text": "Context High intakes of red or processed meat may increase risk of mortality. Objective Determine the relations of red, white and processed meat intakes to risk for total, and cause-specific mortality. Design, Setting, and Participants The NIH-AARP Diet and Health Study cohort of half a million people aged 50-71 years at baseline. Meat intake was estimated from a food frequency questionnaire administered at baseline. Cox proportional hazards regression estimated hazard ratios (HRs) and 95% confidence intervals (CIs) within quintiles of meat intake. The covariates included in the models were: age; education; marital status; family history of cancer (yes/no) (cancer mortality only); race; body mass index; 31-level smoking history; physical activity; energy intake; alcohol intake; vitamin supplement use; fruit consumption; vegetable consumption; and menopausal hormone therapy among women. Main Outcome Measure Total mortality, deaths due to cancer, CVD, accidents, and other causes. Results There were 47,976 male deaths and 23,276 female deaths during 10 years of follow-up. Men and women in the highest versus lowest quintile of red (HR 1.31, 95% CI 1.27-1.35; HR 1.36, 95% CI 1.30-1.43, respectively) and processed meat intake (HR 1.16, 95% CI 1.12-1.20; HR 1.25, 95% 1.20-1.31, respectively) had elevated risks for overall mortality. Regarding cause-specific mortality, men and women had elevated risks for cancer mortality for red (HR 1.22, 95% CI 1.16-1.29; HR 1.20, 95% CI 1.12-1.30, respectively) and processed meats (HR 1.12, 95% CI 1.06-1.19; HR 1.11, 95% CI 1.04-1.19, respectively). Furthermore, CVD risk was elevated for men and women in the highest quintile of red (HR 1.27, 95% CI 1.20-1.35; HR 1.50, 95% CI 1.37-1.65, respectively) and processed meat (HR 1.09, 95% CI 1.03-1.15; HR 1.38, 95% CI 1.26-1.51, respectively). When comparing the highest to the lowest quintile of white meat intake, there was an inverse association for total mortality, and cancer mortality, as well as all other deaths for both men and women. Conclusion Red and processed meat intakes were associated with modest increases in total mortality, cancer mortality and CVD mortality.",
"title": "Meat intake and mortality: a prospective study of over half a million people"
},
{
"docid": "MED-4487",
"text": "Background The evidence that red and processed meat influences colorectal carcinogenesis was judged convincing in the 2007 World Cancer Research Fund/American Institute of Cancer Research report. Since then, ten prospective studies have published new results. Here we update the evidence from prospective studies and explore whether there is a non-linear association of red and processed meats with colorectal cancer risk. Methods and Findings Relevant prospective studies were identified in PubMed until March 2011. For each study, relative risks and 95% confidence intervals (CI) were extracted and pooled with a random-effects model, weighting for the inverse of the variance, in highest versus lowest intake comparison, and dose-response meta-analyses. Red and processed meats intake was associated with increased colorectal cancer risk. The summary relative risk (RR) of colorectal cancer for the highest versus the lowest intake was 1.22 (95% CI = 1.11−1.34) and the RR for every 100 g/day increase was 1.14 (95% CI = 1.04−1.24). Non-linear dose-response meta-analyses revealed that colorectal cancer risk increases approximately linearly with increasing intake of red and processed meats up to approximately 140 g/day, where the curve approaches its plateau. The associations were similar for colon and rectal cancer risk. When analyzed separately, colorectal cancer risk was related to intake of fresh red meat (RR for 100 g/day increase = 1.17, 95% CI = 1.05−1.31) and processed meat (RR for 50 g/day increase = 1.18, 95% CI = 1.10−1.28). Similar results were observed for colon cancer, but for rectal cancer, no significant associations were observed. Conclusions High intake of red and processed meat is associated with significant increased risk of colorectal, colon and rectal cancers. The overall evidence of prospective studies supports limiting red and processed meat consumption as one of the dietary recommendations for the prevention of colorectal cancer.",
"title": "Red and Processed Meat and Colorectal Cancer Incidence: Meta-Analysis of Prospective Studies"
}
] |
PLAIN-3316
|
Muscle Tremors & Diet
|
[
{
"docid": "MED-3939",
"text": "Excerpt This Statistical Brief presents data from the Healthcare Cost and Utilization Project (HCUP) on the treatment of TBI in U.S. hospitals in 2004. Hospital utilization and costs for TBI admissions are compared with hospital stays for all other injuries. Additionally, trends in hospital stays for TBI and differences in the distribution of TBI admissions by various patient characteristics are examined. Finally, common causes of TBIs resulting in hospital admission, as well as the coexisting conditions often associated with these injuries, are described. All differences between estimates noted in the text are statistically significant at the 0.05 level or better.",
"title": "Hospital Admissions for Traumatic Brain Injuries, 2004: Statistical Brief #27"
},
{
"docid": "MED-3938",
"text": "Polychlorinated biphenyls (PCBs) are synthetic chemicals primarily used as coolants and insulators in electrical equipment. Although banned for several decades, PCBs continue to exist in the environment because of their long half-life, continued presence in items produced before the ban, and poor disposal practices. Epidemiological and experimental studies have identified exposure to PCBs as a potential risk factor for Parkinson’s disease, perhaps more so in females. The objective of this work was to examine the association between PCB levels in post-mortem human brain tissue and the diagnosis of Parkinson’s disease, as well as the degree of nigral depigmentation. We also sought to determine if this association was more significant when patients were stratified by sex. Post-mortem brain samples from control patients and those diagnosed with Parkinson’s disease were obtained from the Emory University Brain Bank and from the Nun Study. Concentrations of eight prevalent PCB congeners were extracted from post-mortem brain tissue and analyzed using gas chromatography-mass spectrometry. PCB congeners 153 and 180 were significantly elevated in the brains of Parkinson’s disease patients. When stratified by sex, the female Parkinson’s disease group demonstrated significantly elevated concentrations of total PCBs and specifically congeners 138, 153, and 180 compared to controls, whereas PCB concentrations in males were not significantly different between control and Parkinson’s disease groups. In a separate population of women (Nun Study) who had no clinical signs or symptoms of PD, elevated concentrations total PCB and congeners 138, 153 and 180 were also observed in post-mortem brain tissue exhibiting moderate nigral depigmentation compared to subjects with mild or no depigmentation. These quantitative data demonstrate an association between brain PCB levels and Parkinson’s disease-related pathology. Furthermore, these data support epidemiological and laboratory studies reporting a link between PCB exposure and an increased risk for Parkinson’s disease, including greater susceptibility of females.",
"title": "Association between polychlorinated biphenyls and Parkinson’s disease neuropathology"
},
{
"docid": "MED-4726",
"text": "The aim of these studies was to evaluate the potential of some nutritional approaches to prevent or reduce the body load of organochlorines (OC) in humans. Study 1 compared plasma OC concentrations between vegans and omnivores while study 2 verified if the dietary fat substitute olestra could prevent the increase in OC concentrations that is generally observed in response to a weight-reducing programme. In study 1, nine vegans and fifteen omnivores were recruited and the concentrations of twenty-six OC (beta-hexachlorocyclohexane (beta-HCH), p, p'-dichlorodiphenyldichloroethane (p, p'-DDE), p, p'-dichlorodiphenyltrichloroethane (p, p'-DDT), hexachlorobenzene, mirex, aldrin, alpha-chlordane, gamma-chlordane, oxychlordane, cis-nonachlor, trans-nonachlor, polychlorinated biphenyl (PCB) nos. 28, 52, 99, 101, 105, 118, 128, 138, 153, 156, 170, 180, 183 and 187, and aroclor 1260) were determined. In study 2, the concentrations of these twenty-six OC were measured before and after weight loss over 3 months in thirty-seven obese men assigned to one of the following treatments: standard group (33 % fat diet; n 13), fat-reduced group (25 % fat diet; n 14) or fat-substituted group (1/3 of dietary lipids substituted by olestra; n 10). In study 1, plasma concentrations of five OC compounds (aroclor 1260 and PCB 99, PCB 138, PCB 153 and PCB 180) were significantly lower in vegans compared with omnivores. In study 2, beta-HCH was the only OC which decreased in the fat-substituted group while increasing in the other two groups (P = 0.045). In conclusion, there was a trend toward lesser contamination in vegans than in omnivores, and olestra had a favourable influence on beta-HCH but did not prevent plasma hyperconcentration of the other OC during ongoing weight loss.",
"title": "Impact of adopting a vegan diet or an olestra supplementation on plasma organochlorine concentrations: results from two pilot studies."
},
{
"docid": "MED-3940",
"text": "Objective: To determine whether evidence of neuronal dysfunction or demise preceded deposition of Lewy pathology in vulnerable neurons in Parkinson disease (PD). Methods: We examined the extent of nigral dysfunction and degeneration among 63 normal, incidental Lewy body disease (ILBD), and PD cases based on tyrosine hydroxylase (TH) immunoreactivity and neuron densities, respectively. The relationship between these markers and Lewy pathology (LP) burden in the substantia nigra (SN) and Braak PD stage was assessed. Results: Compared with normal subjects, ILBD cases displayed a significantly higher percentage of TH-negative cells and lower neuronal densities in the SN as early as Braak PD stages 1 and 2, before LP deposition in the nigrostriatal system. ILBD nigral neuron densities were intermediate between normal subjects and PD cases, and TH-negative percentages were higher in ILBD than either normal or PD cases. Furthermore, neuron density and neuronal dysfunction levels remained relatively constant across Braak PD stages in ILBD. Conclusions: These results suggest that significant neurodegeneration and cellular dysfunction precede LP in the SN, challenging the pathogenic role of LP in PD and the assumption that ILBD always represents preclinical PD.",
"title": "Lewy pathology is not the first sign of degeneration in vulnerable neurons in Parkinson disease"
},
{
"docid": "MED-3935",
"text": "Background Parkinson’s disease (PD) is the second most common neurodegenerative disorder. People with PD, their families, scientists, health care providers, and the general public are increasingly interested in identifying environmental contributors to PD risk. Methods In June 2007, a multidisciplinary group of experts gathered in Sunnyvale, California, USA, to assess what is known about the contribution of environmental factors to PD. Results We describe the conclusions around which they came to consensus with respect to environmental contributors to PD risk. We conclude with a brief summary of research needs. Conclusions PD is a complex disorder, and multiple different pathogenic pathways and mechanisms can ultimately lead to PD. Within the individual there are many determinants of PD risk, and within populations, the causes of PD are heterogeneous. Although rare recognized genetic mutations are sufficient to cause PD, these account for < 10% of PD in the U.S. population, and incomplete penetrance suggests that environmental factors may be involved. Indeed, interplay among environmental factors and genetic makeup likely influences the risk of developing PD. There is a need for further understanding of how risk factors interact, and studying PD is likely to increase understanding of other neurodegenerative disorders.",
"title": "Meeting Report: Consensus Statement—Parkinson’s Disease and the Environment: Collaborative on Health and the Environment and Parkinson’s Action Network (CHE PAN) Conference 26–28 June 2007"
},
{
"docid": "MED-4977",
"text": "Background/Aim Harmane [1-methyl-9H-pyrido(3,4-b)indole] is a tremor-producing neurotoxin. Blood harmane concentrations are elevated in essential tremor (ET) patients for unclear reasons. Potential mechanisms include increased dietary harmane intake (especially through well-cooked meat) or genetic-metabolic factors. We tested the hypothesis that meat consumption and level of meat doneness are higher in ET cases than in controls. Methods Detailed data were collected using the Lawrence Livermore National Laboratory Meat Questionnaire. Results Total current meat consumption was greater in men with than without ET (135.3 ± 71.1 vs. 110.6 ± 80.4 g/day, p = 0.03) but not in women with versus without ET (80.6 ± 50.0 vs. 79.3 ± 51.0 g/day, p = 0.76). In an adjusted logistic regression analysis in males, higher total current meat consumption was associated with ET (OR = 1.006, p = 0.04, i.e., with 10 additional g/day of meat, odds of ET increased by 6%). Male cases had higher odds of being in the highest than lowest quartile of total current meat consumption (adjusted OR = 21.36, p = 0.001). Meat doneness level was similar in cases and controls. Conclusion This study provides evidence of a dietary difference between male ET cases and male controls. The etiological ramifications of these results warrant additional investigation. Copyright © 2008 S. Karger AG, Basel",
"title": "Dietary Epidemiology of Essential Tremor: Meat Consumption and Meat Cooking Practices"
},
{
"docid": "MED-3937",
"text": "BACKGROUND: The goal of the present study was to analyze the epidemiology and specific risk factors of traumatic brain injury (TBI) in the Asterix illustrated comic books. Among the illustrated literature, TBI is a predominating injury pattern. METHODS: A retrospective analysis of TBI in all 34 Asterix comic books was performed by examining the initial neurological status and signs of TBI. Clinical data were correlated to information regarding the trauma mechanism, the sociocultural background of victims and offenders, and the circumstances of the traumata, to identify specific risk factors. RESULTS: Seven hundred and four TBIs were identified. The majority of persons involved were adult and male. The major cause of trauma was assault (98.8%). Traumata were classified to be severe in over 50% (GCS 3-8). Different neurological deficits and signs of basal skull fractures were identified. Although over half of head-injury victims had a severe initial impairment of consciousness, no case of death or permanent neurological deficit was found. The largest group of head-injured characters was constituted by Romans (63.9%), while Gauls caused nearly 90% of the TBIs. A helmet had been worn by 70.5% of victims but had been lost in the vast majority of cases (87.7%). In 83% of cases, TBIs were caused under the influence of a doping agent called \"the magic potion\". CONCLUSIONS: Although over half of patients had an initially severe impairment of consciousness after TBI, no permanent deficit could be found. Roman nationality, hypoglossal paresis, lost helmet, and ingestion of the magic potion were significantly correlated with severe initial impairment of consciousness (p ≤ 0.05).",
"title": "Traumatic brain injuries in illustrated literature: experience from a series of over 700 head injuries in the Asterix comic books."
},
{
"docid": "MED-3936",
"text": "Background Exposure to pesticides has been reported to increase the risk of Parkinson disease (PD), but identification of the specific pesticides is lacking. Three studies have found elevated levels of organochlorine pesticides in postmortem PD brains. Objective To determine whether elevated levels of organochlorine pesticides are present in the serum of patients with PD. Design Case-control study. Setting An academic medical center. Participants Fifty patients with PD, 43 controls, and 20 patients with Alzheimer disease. Main Outcome Measures Levels of 16 organochlorine pesticides in serum samples. Results β-Hexachlorocyclohexane (β-HCH) was more often detectable in patients with PD (76%) compared with controls (40%) and patients with Alzheimer disease (30%). The median level of β-HCH was higher in patients with PD compared with controls and patients with Alzheimer disease. There were no marked differences in detection between controls and patients with PD concerning any of the other 15 organochlorine pesticides. Finally, we observed a significant odds ratio for the presence of β-HCH in serum to predict a diagnosis of PD vs control (odds ratio, 4.39; 95% confidence interval, 1.67–11.6) and PD vs Alzheimer disease (odds ratio, 5.20), which provides further evidence for the apparent association between serum β-HCH and PD. Conclusions These data suggest that β-HCH is associated with a diagnosis of PD. Further research is warranted regarding the potential role of β-HCH as a etiologic agent for some cases of PD.",
"title": "Elevated Serum Pesticide Levels and Risk of Parkinson Disease"
}
] |
[
{
"docid": "MED-2178",
"text": "Background Tremor is a widespread phenomenon in human populations. Environmental factors are likely to play an etiological role. Harmane (1-methyl-9H-pyrido[3,4-β]indole) is a potent tremor-producing β-carboline alkaloid. Lead is another tremor-producing neurotoxicant. The effects of harmane and lead with respect to tremor have been studied in isolation. Objectives We tested the hypothesis that tremor would be particularly severe among individuals who had high blood concentrations of both of these toxicants. Methods Blood concentrations of harmane and lead were each quantified in 257 individuals (106 essential tremor cases and 151 controls) enrolled in an environmental epidemiological study. Total tremor score (range = 0 – 36) was a clinical measure of tremor severity. Results The total tremor score ranged from 0 – 36, indicating that a full spectrum of tremor severities was captured in our sample. Blood harmane concentration correlated with total tremor score (p = 0.007), as did blood lead concentration (p = 0.045). The total tremor score was lowest in participants with both low blood harmane and lead concentrations (8.4 ± 8.2), intermediate in participants with high concentrations of either toxicant (10.5 ± 9.8), and highest in participants with high concentrations of both toxicants (13.7 ± 10.4)(p = 0.01). Conclusions Blood harmane and lead concentrations separately correlated with total tremor scores. Participants with high blood concentrations of both toxicants had the highest tremor scores, suggesting an additive effect of these toxicants on tremor severity. Given the very high population prevalence of tremor disorders, identifying environmental determinants is important for primary disease prevention.",
"title": "Blood Harmane, Blood Lead, and Severity of Hand Tremor: Evidence of Additive Effects"
},
{
"docid": "MED-2175",
"text": "BACKGROUND: On proton magnetic resonance spectroscopic imaging ((1)H MRSI), there is a decrease in cerebellar N-acetylaspartate/total creatine (NAA/tCr) in essential tremor (ET), signifying cerebellar neuronal dysfunction or degeneration. Harmane, which is present in the human diet, is a potent tremor-producing neurotoxin. Blood harmane concentrations seem to be elevated in ET. OBJECTIVES: To assess in patients with ET whether blood harmane concentration is correlated with cerebellar NAA/tCR, a neuroimaging measure of neuronal dysfunction or degeneration. METHODS: Twelve patients with ET underwent (1)H MRSI. The major neuroanatomic structure of interest was the cerebellar cortex. Secondary regions were the central cerebellar white matter, cerebellar vermis, thalamus, and basal ganglia. Blood concentrations of harmane and another neurotoxin, lead, were also assessed. RESULTS: Mean +/- SD cerebellar NAA/tCR was 1.52 +/- 0.41. In a linear regression model that adjusted for age and gender, log blood harmane concentration was a predictor of cerebellar NAA/tCR (beta = -0.41, p = 0.009); every 1 g(-10)/mL unit increase in log blood harmane concentration was associated with a 0.41 unit decrease in cerebellar NAA/tCR. The association between blood harmane concentration and brain NAA/tCR only occurred in the cerebellar cortex; it was not observed in secondary brain regions of interest. Furthermore, the association was specific to harmane and not another neurotoxin, lead. CONCLUSION: This study provides additional support for the emerging link between harmane, a neurotoxin, and ET. Further studies are warranted to address whether cerebellar harmane concentrations are associated with cerebellar pathology in postmortem studies of the ET brain.",
"title": "Blood harmane is correlated with cerebellar metabolism in essential tremor: a pilot study."
},
{
"docid": "MED-2174",
"text": "Background Blood concentrations of harmane, a tremor-producing neurotoxin, are elevated in essential tremor (ET). Harmane is also a co-mutagen. Objective To compare the prevalence of cancer in ET cases vs. controls, and determine whether blood harmane concentrations are elevated among ET cases with cancer. Methods Case-control design. Results 66/267 (24.7%) ET cases vs. 55/331 (16.6%) controls had cancer (adjusted OR 1.52, 95% CI 1.01 – 2.30, p = 0.04). Among specific cancer types, colon cancer was more prevalent in ET cases than controls (2.6% vs. 0.6%, p = 0.04). Log blood harmane concentration was higher in ET cases vs. controls (p = 0.02) and in participants with vs. without cancer (p = 0.02). Log blood harmane concentration was highest in ET cases with cancer when compared with other groups (p = 0.009). Discussion These links between cancer and ET and between high blood harmane and cancer in ET deserve further study.",
"title": "Cancer and Blood Concentrations of the Co-mutagen Harmane in Essential Tremor"
},
{
"docid": "MED-2167",
"text": "BACKGROUND: It has been suggested that environmental factors may be associated with essential tremor (ET). This study was carried out to evaluate the association of caffeine intake with ET. METHOD: In a case control study, patients diagnosed with ET and healthy controls underwent a standardized questionnaire interview to evaluate the exposure to coffee and tea intake. A multivariate logistic regression analysis was carried out to evaluate the association of caffeine intake and other environmental factors with risk of ET. RESULTS: 179 subjects including 79 ET patients and 100 controls matched for age, gender and ethnicity were included in the analysis. Univariate analysis revealed that caffeine consumption in ET patients was higher than control group (median and 90th percentile range: 2300 (0, 9000) mg-years versus 1500 (0, 6090) mg-years, p=0.01). However, the multivariate logistic regression analysis demonstrated that caffeine was no longer a significant factor associated with ET (p=0.119). There was no significant correlation between amount of caffeine intake and disease duration (Spearman's r=0.194; p=0.202) or total tremor score (Spearman's r=0.045; p=0.771) in ET patients. CONCLUSION: Caffeine consumption was not associated with risk of ET in our study population. Further studies are needed to investigate the significance of gene-environmental interaction in ET.",
"title": "Exploring the relationship between caffeine intake and essential tremor."
},
{
"docid": "MED-2170",
"text": "Background/Aim Harmane [1-methyl-9H-pyrido(3,4-b)indole] is a tremor-producing neurotoxin. Blood harmane concentrations are elevated in essential tremor (ET) patients for unclear reasons. Potential mechanisms include increased dietary harmane intake (especially through well-cooked meat) or genetic-metabolic factors. We tested the hypothesis that meat consumption and level of meat doneness are higher in ET cases than in controls. Methods Detailed data were collected using the Lawrence Livermore National Laboratory Meat Questionnaire. Results Total current meat consumption was greater in men with than without ET (135.3 ± 71.1 vs. 110.6 ± 80.4 g/day, p = 0.03) but not in women with versus without ET (80.6 ± 50.0 vs. 79.3 ± 51.0 g/day, p = 0.76). In an adjusted logistic regression analysis in males, higher total current meat consumption was associated with ET (OR = 1.006, p = 0.04, i.e., with 10 additional g/day of meat, odds of ET increased by 6%). Male cases had higher odds of being in the highest than lowest quartile of total current meat consumption (adjusted OR = 21.36, p = 0.001). Meat doneness level was similar in cases and controls. Conclusion This study provides evidence of a dietary difference between male ET cases and male controls. The etiological ramifications of these results warrant additional investigation. Copyright © 2008 S. Karger AG, Basel",
"title": "Dietary Epidemiology of Essential Tremor: Meat Consumption and Meat Cooking Practices"
},
{
"docid": "MED-2171",
"text": "Essential tremor (ET) is among the most prevalent neurological diseases, yet its etiology is not well understood. Susceptibility genotypes undoubtedly underlie many ET cases, although no genes have been identified thus far. Environmental factors are also likely to contribute to the etiology of ET. Harmane (1-methyl-9H-pyrido[3,4-β]indole) is a potent, tremor-producing β-carboline alkaloid, and emerging literature has provided initial links between this neurotoxin and ET. In this report, we review this literature. Two studies, both in New York, have demonstrated higher blood harmane levels in ET cases than controls and, in one study, especially high levels in familial ET cases. Replication studies of populations outside of New York and studies of brain harmane levels in ET have yet to be undertaken. A small number of studies have explored several of the biological correlates of exposure to harmane in ET patients. Studies of the mechanisms of this putative elevation of harmane in ET have explored the role of increased dietary consumption, finding weak evidence of increased exogenous intake in male ET cases, and other studies have found initial evidence that the elevated harmane in ET might be due to a hereditarily reduced capacity to metabolize harmane to harmine (7-methoxy-1-methyl-9H-pyrido[3,4-β]-indole). Studies of harmane and its possible association with ET have been intriguing. Additional studies are needed to establish more definitively whether these toxic exposures are associated with ET and are of etiological importance.",
"title": "β-Carboline Alkaloids and Essential Tremor: Exploring the Environmental Determinants of One of the Most Prevalent Neurological Diseases"
},
{
"docid": "MED-2166",
"text": "Essential tremor (ET) is a widespread late-life neurological disease. Genetic and environmental factors are likely to play important etiological roles. Harmane (1-methyl-9H-pyrido[3,4-b]indole) is a potent tremor-producing neurotoxin. Previously, elevated blood harmane concentrations were demonstrated in ET cases compared to controls, but these observations were all been cross-sectional, assessing each subject at only one time point. Thus, no one has ever repeat-assayed blood harmane in the same subjects twice. Whether the observed case-control difference persists at a second time point, years later, is unknown. The current goal was to re-assess a sample of our ET cases and controls to determine whether blood harmane concentration remained elevated in ET at a second time point. Blood harmane concentrations were quantified by a well-established high performance liquid chromatography method in 63 ET cases and 70 controls. A mean of approximately 6 years elapsed between the initial and this subsequent blood harmane determination. The mean log blood harmane concentration was significantly higher in cases than controls (0.30 ± 0.61 g−10/ml vs. 0.08 ± 0.55 g−10/ml), and the median value in cases was double that of controls: 0.22 g−10/ml vs. 0.11 g−10/ml. The log blood harmane concentration was highest in cases with a family history of ET. Blood harmane concentration was elevated in ET cases compared to controls when re-assessed at a second time point several years later, indicating what seems to be a stable association between this environmental toxin and ET.",
"title": "Blood Harmane (1-methyl-9h-pyrido[3,4-b]indole) Concentrations in Essential Tremor: Repeat Observation in Cases and Controls in New York"
},
{
"docid": "MED-3925",
"text": "This study describes how foods rich in fisetin and hexacosanol added to a strict diet reversed most symptoms of Parkinson's disease (PD) in one patient. This is a case report involving outpatient care. The subject was a dietitian diagnosed with idiopathic PD in 2000 at the age of 53 years old, with a history of exposure to neurotoxins and no family history of PD. A basic diet started in 2000 consisted of predominantly fruits, vegetables, 100% whole grains, extra virgin olive oil, nuts, seeds, nonfat milk products, tea, coffee, spices, small amounts of dark chocolate, and less than 25 g of animal fat daily. The basic diet alone failed to prevent decline due to PD. In 2009, the basic diet was enhanced with a good dietary source of both fisetin and hexacosanol. Six months after the patient started the enhanced diet rich in fisetin and hexacosanol, a clinically significant improvement in symptoms was noted; the patient's attending neurologist reported that the clinical presentation of cogwheel rigidity, micrographia, bradykinesia, dystonia, constricted arm swing with gait, hypomimia, and retropulsion appeared to be resolved. The only worsening of symptoms occurred when the diet was not followed precisely. Little improvement in tremor or seborrhea was observed. The clinical improvement has persisted to date. To the best of our knowledge, this is the first case where adjunctive diet therapy resulted in a significant reduction of symptoms of PD without changing the type or increasing the amount of medications.",
"title": "A diet low in animal fat and rich in N-hexacosanol and fisetin is effective in reducing symptoms of Parkinson's disease."
},
{
"docid": "MED-1465",
"text": "An increased intramyocellular lipid (IMCL) content, as quantified by (1)H-magnetic resonance spectroscopy ((1)H-MRS), is associated with reduced insulin sensitivity. At present, it is unclear which factors determine IMCL formation and how rapidly IMCL accumulation can be induced. We therefore studied the impact of hyperinsulinemia and elevated circulating nonesterified fatty acid (NEFA) levels on IMCL formation and insulin sensitivity. We further evaluated the influence of a high-fat diet on IMCL storage. In the infusion protocol, 12 healthy male subjects underwent a 6-h hyperinsulinemic-euglycemic glucose clamp with concomitant infusion of Intralipid plus heparin. IMCL was quantified by (1)H-MRS in soleus (SOL) and tibialis anterior (TA) muscle at baseline and then every hour. IMCL levels started to increase significantly after 2 h, reaching a maximum of 120.8 +/- 3.4% (SOL) and 164.2 +/- 13.8% (TA) of baseline after 6 h (both P < 0.05). In parallel, the glucose infusion rate (GIR) decreased progressively, reaching a minimum of 60.4 +/- 5.4% of baseline after 6 h. Over time, the GIR was strongly correlated with IMCL in TA (r = -0.98, P < or = 0.003) and SOL muscle (r = -0.97, P < or = 0.005). In the diet protocol, 12 male subjects ingested both a high-fat and low-fat diet for 3 days each. Before and after completion of each diet, IMCL levels and insulin sensitivity were assessed. After the high-fat diet, IMCL levels increased significantly in TA muscle (to 148.0 +/- 16.9% of baseline; P = 0.005), but not in SOL muscle (to 114.4 +/- 8.2% of baseline; NS). Insulin sensitivity decreased to 83.3 +/- 5.6% of baseline (P = 0.033). There were no significant changes in insulin sensitivity or IMCL levels after the low-fat diet. The effects of the high-fat diet showed greater interindividual variation than those of the infusion protocol. The data from the lipid infusion protocol suggest a functional relationship between IMCL levels and insulin sensitivity. Similar effects could be induced by a high-fat diet, thereby underlining the physiological relevance of these observations.",
"title": "Effects of intravenous and dietary lipid challenge on intramyocellular lipid content and the relation with insulin sensitivity in humans."
},
{
"docid": "MED-2164",
"text": "Essential tremor (ET) is among the more prevalent neurological disorders, yet prevalence estimates have varied enormously, making it difficult to establish prevalence with precision. We: (1) reviewed the worldwide prevalence of ET in population-based epidemiological studies, (2) derived as precisely as possible an estimate of disease prevalence, and (3) examined trends and important differences across studies. We identified 28 population-based prevalence studies (19 countries). In a meta-analysis, pooled prevalence (all ages) = 0.9%, with statistically significant heterogeneity across studies (I(2) = 99%, P < 0.001). In additional descriptive analyses, crude prevalence (all ages) = 0.4%. Prevalence increased markedly with age, and especially with advanced age. In the meta-analysis, prevalence (age >or= 65 years) = 4.6%, and in additional descriptive analyses, median crude prevalence (age >or= 60-65) = 6.3%. In one study of those age >or= 95 years, crude prevalence = 21.7%. Several studies reported ethnic differences in prevalence, although more studies are needed. Greater than one-third of studies show a gender difference, with most demonstrating a higher prevalence among men. This possible gender preference is interesting given clinical, epidemiological, and pathological associations between ET and Parkinson's disease. Precise prevalence estimates such as those we provide are important because they form the numerical basis for planned public health initiatives, provide data on the background occurrence of disease for family studies, and offer clues about the existence of environmental or underlying biological factors of possible mechanistic importance. (c) 2010 Movement Disorder Society.",
"title": "How common is the most common adult movement disorder? Update on the worldwide prevalence of essential tremor."
},
{
"docid": "MED-1466",
"text": "Rat muscle studies suggest competition between free fatty acids (FFA) and glucose for oxidation, resulting in glucose-6-phosphate accumulation. However, FFA decrease glucose-6-phosphate in human skeletal muscle, indicating direct inhibition of glucose transport/phosphorylation. This mechanism could redirect glucose from muscle to brain during fasting and explain the insulin resistance associated with high-lipid diets and obesity.",
"title": "How free fatty acids inhibit glucose utilization in human skeletal muscle."
},
{
"docid": "MED-3024",
"text": "This experiment aimed to study the molecular toxicity of methylmercury (MeHg) in liver, brain and white muscle of Atlantic salmon fed a diet based on fish oil (FO, high dietary n-3/n-6 ratio) compared to an alternative diet mainly based on vegetable oil (VO, low dietary n-3/n-6 ratio). Juvenile salmon were fed decontaminated diets or the FO and VO diets enriched with 5 mg Hg/kg (added as MeHg) for three months. The dietary lipid composition affected the fatty acid composition in the tissues, especially in liver and white muscle. After 84 days of exposure, the liver accumulated three times as much MeHg as the brain and white muscle. Vitamin C content and heme oxygenase, tubulin alpha (TUBA) and Cpt1 transcriptional levels all showed significant effects of MeHg exposure in the liver. TBARS, α-tocopherol, γ-tocopherol, and the transcriptional levels of thioredoxin, heme oxygenase, TUBA, PPARB1, D5D and D6D showed an effect of dietary lipid composition in liver tissue. Effects of dietary lipids were observed in brain tissue for MT-A, HIF1, Bcl-X and TUBA. Interaction effects between MeHg exposure and dietary lipid composition were observed in all tissues. Our data suggest that dietary fats have modulating effects on MeHg toxicity in Atlantic salmon. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Dietary lipids modulate methylmercury toxicity in Atlantic salmon."
},
{
"docid": "MED-3220",
"text": "Background Maintaining muscle mass while aging is important to prevent falls and fractures. Metabolic acidosis promotes muscle wasting, and the net acid load from diets that are rich in net acid–producing protein and cereal grains relative to their content of net alkali–producing fruit and vegetables may therefore contribute to a reduction in lean tissue mass in older adults. Objective We aimed to determine whether there was an association of 24-h urinary potassium and an index of fruit and vegetable content of the diet with the percentage lean body mass (%LBM) or change in %LBM in older subjects. Design Subjects were 384 men and women ≥65 y old who participated in a 3-y trial comparing calcium and vitamin D with placebo. Potassium was measured in 24-h urine collections at baseline. The %LBM, defined as total body nonfat, nonbone tissue weight ÷ weight × 100, was measured by using dual-energy X-ray absorptiometry at baseline and at 3 y. Physical activity, height, and weight were assessed at baseline and at 3 y. Results At baseline, the mean urinary potassium excretion was 67.0 ± 21.1 mmol/d. Urinary potassium (mmol/d) was significantly positively associated with %LBM at baseline (β = 0.033, P = 0.006; adjusted for sex, weight, and nitrogen excretion) but not with 3-y change in %LBM. Over the 3-y study, %LBM increased by 2.6 ± 3.6%. Conclusion Higher intake of foods rich in potassium, such as fruit and vegetables, may favor the preservation of muscle mass in older men and women.",
"title": "Alkaline diets favor lean tissue mass in older adults"
},
{
"docid": "MED-3235",
"text": "Background Maintaining muscle mass while aging is important to prevent falls and fractures. Metabolic acidosis promotes muscle wasting, and the net acid load from diets that are rich in net acid–producing protein and cereal grains relative to their content of net alkali–producing fruit and vegetables may therefore contribute to a reduction in lean tissue mass in older adults. Objective We aimed to determine whether there was an association of 24-h urinary potassium and an index of fruit and vegetable content of the diet with the percentage lean body mass (%LBM) or change in %LBM in older subjects. Design Subjects were 384 men and women ≥65 y old who participated in a 3-y trial comparing calcium and vitamin D with placebo. Potassium was measured in 24-h urine collections at baseline. The %LBM, defined as total body nonfat, nonbone tissue weight ÷ weight × 100, was measured by using dual-energy X-ray absorptiometry at baseline and at 3 y. Physical activity, height, and weight were assessed at baseline and at 3 y. Results At baseline, the mean urinary potassium excretion was 67.0 ± 21.1 mmol/d. Urinary potassium (mmol/d) was significantly positively associated with %LBM at baseline (β = 0.033, P = 0.006; adjusted for sex, weight, and nitrogen excretion) but not with 3-y change in %LBM. Over the 3-y study, %LBM increased by 2.6 ± 3.6%. Conclusion Higher intake of foods rich in potassium, such as fruit and vegetables, may favor the preservation of muscle mass in older men and women.",
"title": "Alkaline diets favor lean tissue mass in older adults"
},
{
"docid": "MED-4144",
"text": "Ractopamine hydrochloride (RAC) has consistently led to an advantage in carcass cutting yields of finishing pigs and remains a common feed additive in US finishing pig diets. Less is known about the effect of RAC on further processing characteristics. Some researchers have reported advantages in ultimate pH of the LM in pigs fed RAC. If a greater ultimate pH was also observed in hams, the increased pH could affect further processing characteristics and lead to better protein interaction and improved textural properties. The objective of this experiment was to determine if RAC-fed pigs yielded hams with a greater ultimate pH, and if so, whether or not that advantage improves textural properties and water retention of further processed hams. Two hundred hams from barrows and gilts fed RAC or control diets were selected based on HCW. Hams were fabricated into 5 separate pieces to determine cutting yields, and 6 muscles were evaluated for ultimate pH. Hams were processed to make cured and smoked hams. Ractopamine increased cutting yields of the whole ham (P < 0.0001), inside (P < 0.01), outside (P < 0.01), and knuckle (P < 0.01) when expressed as a percentage of chilled side weight. Ultimate pH of the rectus femoris, vastus lateralis, and semitendinosus were all 0.06 pH units greater (P < 0.05), the biceps femoris was 0.04 pH units greater (P = 0.02), and the semimembranosus and adductor muscles were 0.03 pH units greater in pigs fed 7.4 mg/kg of RAC when compared with control pigs. Cured hams from RAC-fed pigs were heavier at all stages of production. No differences were detected in binding strengths (P = 0.88) or protein fat-free values (P = 0.13) between RAC (9.06 kg and 20.37) and control hams (9.01 kg and 20.13). Ractopamine increased cutting yields, total weight of cured hams, and ultimate muscle pH. Ractopamine can be fed to pigs to achieve the desired growth characteristic advantages and cutting yields without affecting further processed ham characteristics.",
"title": "Fresh meat and further processing characteristics of ham muscles from finishing pigs fed ractopamine hydrochloride."
},
{
"docid": "MED-4626",
"text": "Chicken meat with reduced concentration of arachidonic acid (AA) and reduced ratio between omega-6 and omega-3 fatty acids has potential health benefits because a reduction in AA intake dampens prostanoid signaling, and the proportion between omega-6 and omega-3 fatty acids is too high in our diet. Analyses for fatty acid determination are expensive, and finding the optimal number of analyses to give reliable results is a challenge. The objective of the present study was i) to analyse the intraclass correlation of different fatty acids in five meat samples, of one gram each, within the same chicken thigh, and ii) to study individual variations in the concentrations of a range of fatty acids and the ratio between omega-6 and omega-3 fatty acid concentrations among fifteen chickens. Fifteen newly hatched broilers were fed a wheat-based diet containing 4% rapeseed oil and 1% linseed oil for three weeks. Five muscle samples from the mid location of the thigh of each chicken were analysed for fatty acid composition. The intraclass correlation (sample correlation within the same animal) was 0.85-0.98 for the ratios of total omega-6 to total omega-3 fatty acids and of AA to eicosapentaenoic acid (EPA). This indicates that when studying these fatty acid ratios, one sample of one gram per animal is sufficient. However, due to the high individual variation between chicken for these ratios, a relatively high number of animals (minimum 15) are required to obtain a sufficiently high power to reveal significant effects of experimental factors (e.g. feeding regimes). The present experiment resulted in meat with a favorable concentration ratio between omega-6 and omega-3 fatty acids. The AA concentration varied from 1.5 to 2.8 g/100 g total fatty acids in thigh muscle in the fifteen broilers, and the ratio between AA and EPA concentrations ranged from 2.3 to 3.9. These differences among the birds may be due to genetic variance that can be exploited by breeding for lower AA concentration and/or a more favorable AA/EPA ratio to produce meat with health benefits.",
"title": "Individual variation and intraclass correlation in arachidonic acid and eicosapentaenoic acid in chicken muscle"
},
{
"docid": "MED-1457",
"text": "Obesity and type 2 diabetes have been associated with a high-fat diet (HFD) and reduced mitochondrial mass and function. We hypothesized a HFD may affect expression of genes involved in mitochondrial function and biogenesis. To test this hypothesis, we fed 10 insulin-sensitive males an isoenergetic HFD for 3 days with muscle biopsies before and after intervention. Oligonucleotide microarray analysis revealed 297 genes were differentially regulated by the HFD (Bonferonni adjusted P < 0.001). Six genes involved in oxidative phosphorylation (OXPHOS) decreased. Four were members of mitochondrial complex I: NDUFB3, NDUFB5, NDUFS1, and NDUFV1; one was SDHB in complex II and a mitochondrial carrier protein SLC25A12. Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC1) alpha and PGC1beta mRNA were decreased by -20%, P < 0.01, and -25%, P < 0.01, respectively. In a separate experiment, we fed C57Bl/6J mice a HFD for 3 weeks and found that the same OXPHOS and PGC1 mRNAs were downregulated by approximately 90%, cytochrome C and PGC1alpha protein by approximately 40%. Combined, these results suggest a mechanism whereby HFD downregulates genes necessary for OXPHOS and mitochondrial biogenesis. These changes mimic those observed in diabetes and insulin resistance and, if sustained, may result in mitochondrial dysfunction in the prediabetic/insulin-resistant state.",
"title": "A high-fat diet coordinately downregulates genes required for mitochondrial oxidative phosphorylation in skeletal muscle."
},
{
"docid": "MED-4747",
"text": "In contrast to the use of hormonal doping agents in sports to enhance the performance of athletes, in the livestock industry hormonal growth promoters (\"anabolics\") are used to increase the production of muscle meat. This leads to international disputes about the safety of meat originating from animals treated with such anabolics.As a consequence of the total ban in the EU of all hormonal active growth promoters (\"hormones\") in livestock production, in contrast to their legal use [e.g. of five such hormones (17beta-estradiol, testosterone, progesterone, trenbolone and zeranol) as small solid ear implants and two hormones as feed additives for feedlot heifers (melengestrol acetate) and for swine (ractopamine) in the USA], the regulatory controls also differ sharply between the EU and the USA.In the EU the treatment of slaughter animals is the regulatory offence that has to be controlled in inspection programs. In the USA testing for compliance of a regulatory maximum residue level in the edible product (muscle, fat, liver or kidney) is the purpose of the inspection program (if any).The EU inspection programs focus on sample materials that are more suitable for testing for banned substances, especially if the animals are still on the farm, such as urine and feces or hair. In the case of slaughtered animals, the more favored sample materials are bile, blood, eyes and sometimes liver. Only in rare occasions is muscle meat sampled. This happens only in the case of import controls or in monitoring programs of meat sampled in butcher shops or supermarkets.As a result, data on hormone concentrations in muscle meat samples from the EU market are very rare and are obtained in most cases from small programs on an ad hoc basis. EU data for natural hormones in meat are even rarer because of the absence of \"legal natural levels\" for these hormones in compliance testing. With the exception of samples from the application sites - in the EU the site of injection of liquid hormone preparations or the site of application of \"pour on\" preparations - the hormone concentrations observed in meat samples of illegally treated animals are typically in the range of a few micrograms per kilogram (ppb) down to a few tenths of a microgram per kilogram. In the EU dozens of illegal hormones are used and the number of active compounds is still expanding. Besides estrogenic, androgenic and progestagenic compounds also thyreostatic, corticosteroidal and beta-adrenergic compounds are used alone or in \"smart\" combinations.An overview is given of the compounds identified on the EU black market. An estimate is also given of the probability of consumption in the EU of \"highly\" contaminated meat from the application sites in cattle. Finally some data are presented on the concentration of estradiol in bovine meat from animals treated and not treated with hormone implants. These data are compared with the recent findings for estradiol concentrations in hen's eggs. From this comparison, the preliminary conclusion is that hen's eggs are the major source of 17alpha- and 17beta-estradiol in the consumer's daily \"normal\" diet.",
"title": "Hormonal growth promoting agents in food producing animals."
},
{
"docid": "MED-4961",
"text": "While fish consumption is considered a component of a heart-healthy diet, many illnesses have been associated with eating contaminated fish. The authors describe two cases of muscle weakness and rhabdomyolysis that occurred after eating salmon. Cases of rhabdomyolysis and muscle weakness after consumption of fresh water fish have rarely been reported in the United States but have been frequently reported from the Baltic region. This illness is known as Haff disease. While the etiology is unknown, it is felt to be a toxin. Palytoxin, found in marine fish, has been associated with rhabdomyolysis, and may serve as a model for further study of the suspected toxin responsible for rhabdomyolysis after consumption of fresh water fish. If a case of Haff disease is suspected, contact the Centers for Disease Control and Prevention and collect any uneaten fish, which may be sent for laboratory analysis.",
"title": "Haff disease after eating salmon."
},
{
"docid": "MED-4828",
"text": "Background Many patients taking statins often complain of muscle pain and weakness. The extent to which muscle pain reflects muscle injury is unknown. Methods We obtained biopsy samples from the vastus lateralis muscle of 83 patients. Of the 44 patients with clinically diagnosed statin-associated myopathy, 29 were currently taking a statin, and 15 had discontinued statin therapy before the biopsy (minimal duration of discontinuation 3 weeks). We also included 19 patients who were taking statins and had no myopathy, and 20 patients who had never taken statins and had no myopathy. We classified the muscles as injured if 2% or more of the muscle fibres in a biopsy sample showed damage. Using reverse transcriptase polymerase chain reaction, we evaluated the expression levels of candidate genes potentially related to myocyte injury. Results Muscle injury was observed in 25 (of 44) patients with myopathy and in 1 patient without myopathy. Only 1 patient with structural injury had a circulating level of creatine phosphokinase that was elevated more than 1950 U/L (10× the upper limit of normal). Expression of ryanodine receptor 3 was significantly upregulated in patients with biopsy evidence of structural damage (1.7, standard error of the mean 0.3). Interpretation Persistent myopathy in patients taking statins reflects structural muscle damage. A lack of elevated levels of circulating creatine phosphokinase does not rule out structural muscle injury. Upregulation of the expression of ryanodine receptor 3 is suggestive of an intracellular calcium leak.",
"title": "Association between statin-associated myopathy and skeletal muscle damage"
},
{
"docid": "MED-3462",
"text": "Immediate and delayed-onset muscle soreness differ mainly in chronology of presentation. Both conditions share the same quality of pain, eliciting and relieving activities and a varying degree of functional deficits. There is no single mechanism for muscle soreness; instead, it is a culmination of 6 different mechanisms. The developing pathway of DOMS begins with microtrauma to muscles and then surrounding connective tissues. Microtrauma is then followed by an inflammatory process and subsequent shifts of fluid and electrolytes. Throughout the progression of these events, muscle spasms may be present, exacerbating the overall condition. There are a multitude of modalities to manage the associated symptoms of immediate soreness and DOMS. Outcomes of each modality seem to be as diverse as the modalities themselves. The judicious use of NSAIDs and continued exercise are suggested to be the most reliable methods and recommended. This review article and each study cited, however, represent just one part of the clinician's decisionmaking process. Careful affirmation of temporary deficits from muscle soreness is not to be taken lightly, nor is the advisement and medical management of muscle soreness prescribed by the clinician.",
"title": "Muscle soreness and delayed-onset muscle soreness."
},
{
"docid": "MED-1474",
"text": "PURPOSE OF REVIEW: Acute exposure to fatty acids causes insulin resistance in muscle, and excess dietary lipid and obesity are also strongly associated with muscle insulin resistance. Relevant mechanisms, however, are still not fully elucidated. Here we examine the latest evidence as to why lipids might accumulate in muscle and the possible mechanisms for lipid-induced insulin resistance. RECENT FINDINGS: Muscle lipid metabolites such as long chain fatty acid coenzyme As, diacylglycerol and ceramides may impair insulin signalling directly. Crosstalk between inflammatory signalling pathways and insulin signalling pathways, mitochondrial dysfunction and oxidative stress have also been put forward as major contributors to the development or maintenance of lipid-induced insulin resistance in muscle. Several animal models with gene deletions in pathways of fatty acid synthesis and storage also show increased metabolic rate, reduced intramuscular lipid storage and improved insulin action when challenged with a high lipid load. SUMMARY: Studies in genetic and dietary obese animal models, genetically modified animals and humans with obesity or type 2 diabetes suggest plausible mechanisms for effects of fatty acids, lipid metabolites, inflammatory pathways and mitochondrial dysfunction on insulin action in muscle. Many of these mechanisms, however, have been demonstrated in situations in which lipid accumulation (obesity) already exists. Whether the initial events leading to muscle insulin resistance are direct effects of fatty acids in muscle or are secondary to lipid accumulation in adipose tissue or liver remains to be clarified.",
"title": "Free fatty acids and skeletal muscle insulin resistance."
},
{
"docid": "MED-3231",
"text": "This review looks at the role of an alkaline diet in health. Pubmed was searched looking for articles on pH, potential renal acid loads, bone health, muscle, growth hormone, back pain, vitamin D and chemotherapy. Many books written in the lay literature on the alkaline diet were also reviewed and evaluated in light of the published medical literature. There may be some value in considering an alkaline diet in reducing morbidity and mortality from chronic diseases and further studies are warranted in this area of medicine.",
"title": "The Alkaline Diet: Is There Evidence That an Alkaline pH Diet Benefits Health?"
},
{
"docid": "MED-4166",
"text": "Antibiotics are used by veterinarians and producers to treat disease and improve animal production. The federal government, to ensure the safety of the food supply, establishes antibiotic residue tolerances in edible animal tissues and determines the target tissues (e.g., muscle) for residue monitoring. However, when muscle is selected as the target tissue, the federal government does not specify which type of muscle tissue is used for monitoring (e.g., breast versus thigh). If specific muscle tissues incorporate residues at higher concentrations, these tissues should be selected for residue monitoring. To evaluate this possibility in poultry, chickens were divided into four groups and at 33 days of age were dosed with enrofloxacin (Baytril), as per label directions, at either 25 ppm for 3 days, 25 ppm for 7 days, 50 ppm for 3 days, or 50 ppm for 7 days. Breast and thigh muscle tissues were collected from each bird (n = 5 birds per day per group) during the dosing and withdrawal period, and fluoroquinolone concentrations were determined. The results indicate higher overall enrofloxacin concentrations in breast versus thigh muscle for each treatment group (P < 0.05). These data indicate, at least for enrofloxacin, that not all muscle tissues incorporate antibiotics at the same concentrations. These results may be helpful to regulatory agencies as they determine what tissues are to be monitored to ensure that the established residue safety tolerance levels are not exceeded.",
"title": "Concentrations of antibiotic residues vary between different edible muscle tissues in poultry."
},
{
"docid": "MED-3460",
"text": "Massage therapy is commonly used during physical rehabilitation of skeletal muscle to ameliorate pain and promote recovery from injury. Although there is evidence that massage may relieve pain in injured muscle, how massage affects cellular function remains unknown. To assess the effects of massage, we administered either massage therapy or no treatment to separate quadriceps of 11 young male participants after exercise-induced muscle damage. Muscle biopsies were acquired from the quadriceps (vastus lateralis) at baseline, immediately after 10 min of massage treatment, and after a 2.5-hour period of recovery. We found that massage activated the mechanotransduction signaling pathways focal adhesion kinase (FAK) and extracellular signal-regulated kinase 1/2 (ERK1/2), potentiated mitochondrial biogenesis signaling [nuclear peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α)], and mitigated the rise in nuclear factor κB (NFκB) (p65) nuclear accumulation caused by exercise-induced muscle trauma. Moreover, despite having no effect on muscle metabolites (glycogen, lactate), massage attenuated the production of the inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and reduced heat shock protein 27 (HSP27) phosphorylation, thereby mitigating cellular stress resulting from myofiber injury. In summary, when administered to skeletal muscle that has been acutely damaged through exercise, massage therapy appears to be clinically beneficial by reducing inflammation and promoting mitochondrial biogenesis.",
"title": "Massage therapy attenuates inflammatory signaling after exercise-induced muscle damage."
},
{
"docid": "MED-1752",
"text": "The transforming growth factor-beta (TGF-beta) superfamily encompasses a large group of growth and differentiation factors playing important roles in regulating embryonic development and in maintaining tissue homeostasis in adult animals. Using degenerate polymerase chain reaction, we have identified a new murine TGF-beta family member, growth/differentiation factor-8 (GDF-8), which is expressed specifically in developing and adult skeletal muscle. During early stages of embryogenesis, GDF-8 expression is restricted to the myotome compartment of developing somites. At later stages and in adult animals, GDF-8 is expressed in many different muscles throughout the body. To determine the biological function of GDF-8, we disrupted the GDF-8 gene by gene targeting in mice. GDF-8 null animals are significantly larger than wild-type animals and show a large and widespread increase in skeletal muscle mass. Individual muscles of mutant animals weigh 2-3 times more than those of wild-type animals, and the increase in mass appears to result from a combination of muscle cell hyperplasia and hypertrophy. These results suggest that GDF-8 functions specifically as a negative regulator of skeletal muscle growth.",
"title": "Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member."
},
{
"docid": "MED-4830",
"text": "Muscle pain and weakness are frequent complaints in patients receiving 3-hydroxymethylglutaryl coenzymeA (HMG CoA) reductase inhibitors (statins). Many patients with myalgia have creatine kinase levels that are either normal or only marginally elevated, and no obvious structural defects have been reported in patients with myalgia only. To investigate further the mechanism that mediates statin-induced skeletal muscle damage, skeletal muscle biopsies from statin-treated and non-statin-treated patients were examined using both electron microscopy and biochemical approaches. The present paper reports clear evidence of skeletal muscle damage in statin-treated patients, despite their being asymptomatic. Though the degree of overall damage is slight, it has a characteristic pattern that includes breakdown of the T-tubular system and subsarcolemmal rupture. These characteristic structural abnormalities observed in the statin-treated patients were reproduced by extraction of cholesterol from skeletal muscle fibres in vitro. These findings support the hypothesis that statin-induced cholesterol lowering per se contributes to myocyte damage and suggest further that it is the specific lipid/protein organization of the skeletal muscle cell itself that renders it particularly vulnerable. Copyright (c) 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.",
"title": "Statin therapy induces ultrastructural damage in skeletal muscle in patients without myalgia."
},
{
"docid": "MED-4829",
"text": "BACKGROUND: Statin therapy can cause myopathy, however it is unclear whether this exacerbates age-related muscle function declines. AIM: To describe differences between statin users and non-users in muscle mass, muscle function and falls risk in a group of community-dwelling older adults. DESIGN: A prospective, population-based cohort study with a mean follow-up of 2.6 years. METHODS: Total 774 older adults [48% female; mean (standard deviation) age = 62 (7) years] were examined at baseline and follow-up. Differences in percentage appendicular lean mass (%ALM), leg strength, leg muscle quality (LMQ; specific force) and falls risk were compared for statin users and non-users. RESULTS: There were 147 (19%) statin users at baseline and 179 (23%) at follow-up. Longitudinal analyses revealed statin use at baseline predicted increased falls risk scores over 2.6 years (0.14, 95% CI 0.01 to 0.27) and a trend towards increased %ALM (0.45%, 95% CI -0.01 to 0.92). Statin users at both time points demonstrated decreased leg strength (-5.02 kg, 95% CI -9.65 to -0.40) and LMQ (-0.30 kg/kg, 95% CI -0.59 to -0.01), and trended towards increased falls risk (0.13, 95% CI -0.01 to 0.26) compared to controls. Finally, statin users at both baseline and follow-up demonstrated decreased leg strength (-16.17 kg, 95% CI -30.19 to -2.15) and LMQ (-1.13 kg/kg, 95% CI -2.02 to -0.24) compared to those who had ceased statin use at follow-up. CONCLUSION: Statin use may exacerbate muscle performance declines and falls risk associated with aging without a concomitant decrease in muscle mass, and this effect may be reversible with cessation.",
"title": "Statin therapy, muscle function and falls risk in community-dwelling older adults."
},
{
"docid": "MED-1460",
"text": "Insulin resistance condition is associated to the development of several syndromes, such as obesity, type 2 diabetes mellitus and metabolic syndrome. Although the factors linking insulin resistance to these syndromes are not precisely defined yet, evidence suggests that the elevated plasma free fatty acid (FFA) level plays an important role in the development of skeletal muscle insulin resistance. Accordantly, in vivo and in vitro exposure of skeletal muscle and myocytes to physiological concentrations of saturated fatty acids is associated with insulin resistance condition. Several mechanisms have been postulated to account for fatty acids-induced muscle insulin resistance, including Randle cycle, oxidative stress, inflammation and mitochondrial dysfunction. Here we reviewed experimental evidence supporting the involvement of each of these propositions in the development of skeletal muscle insulin resistance induced by saturated fatty acids and propose an integrative model placing mitochondrial dysfunction as an important and common factor to the other mechanisms.",
"title": "Mechanisms underlying skeletal muscle insulin resistance induced by fatty acids: importance of the mitochondrial function"
},
{
"docid": "MED-923",
"text": "The effects of glucocorticoid on lipid metabolism of broiler chicken (Gallus gallus domesticus) skeletal muscle were investigated. Male Arbor Acres chickens (35 days old) were subjected to dexamethasone treatment for 3 days. We found that dexamethasone retards body growth while facilitating lipid accumulation. In M. pectoralis major (PM), dexamethasone increased the expression of glucocorticoid receptor (GR), fatty acid transport protein 1 (FATP1), heart fatty acid-binding protein (H-FABP) and long-chain acyl-CoA dehydrogenase (LCAD) mRNA and decreased the expression of liver carnitine palmitoyltransferase 1 (L-CPT1), adenosine-monophosphate-activated protein kinase (AMPK) α2 and lipoprotein lipase (LPL) mRNA. LPL activity was also decreased. In M. biceps femoris (BF), the levels of GR, FATP1 and L-CPT1 mRNA were increased. AMPKα (Thr172) phosphorylation and CTP1 activity of skeletal muscle were decreased by dexamethasone. In fed chickens, dexamethasone enhanced very low-density lipoprotein receptor (VLDLR) expression and AMPK activity in muscle, but it impaired the expression of LPL and L-CPT1 mRNA and LPL activity in PM and augmented the expression of GR, LPL, H-FABP, L-CPT1, LCAD and AMPKα2 mRNA in BF. Adipose triglyceride lipase (ATGL) protein expression was not affected by dexamethasone. In conclusion, in the fasting state, dexamethasone-induced-retarded fatty acid utilisation may be involved in the augmented intramyocellular lipid accumulation in both glycolytic (PM) and oxidative (BF) muscle tissues. In the fed state, dexamethasone promoted the transcriptional activity of genes related to lipid uptake and oxidation in muscles. Unmatched lipid uptake and utilisation are suggested to be involved in the augmented intramyocellular lipid accumulation.",
"title": "Dexamethasone facilitates lipid accumulation in chicken skeletal muscle."
}
] |
1822
|
If a employers supposed to calulate drive time pay with your weekly gross pay
|
[
{
"docid": "192843",
"text": "\"Reimbursements for business expenses are generally not taxable, but the commute from home to the job and back is not considered business travel and if they're paying for that it is taxable income. I don't think carpooling changes that, but I am not a tax lawyer or accountant. The rest of your questions seem to be company policy issues. There is no \"\"should\"\" here. You aren't required to pick up the other guys, but he isn't required to reimburse those miles (or employ you) so think carefully about your priorities before pushing back. Never invoke what thou canst not banish.\"",
"title": ""
},
{
"docid": "214143",
"text": "\"You're getting paid by the job, not by the hour, so I don't see why you think the employer is obligated to pay you for the drive time. The only way that might be true, as far as I can see, is if he were avoiding paying you minimum wage by structuring your employment this way. It looks like to me you're over the minimum wage based on what you wrote. At maximum \"\"unpaid\"\" drive time (59 min each way) and maximum length of job (4 hours as you stated it), gives your minimum hourly rate of $8.83/hr. The federal minimum wage is currently $7.25/hr, so you're over that. A quick search online suggests that NV does have a higher minimum at $8.25/hr under some conditions, but you're still over that too. The fact that you're required to pick-up the helpers and that you have a company car at home probably does mean that you're \"\"on the clock\"\" from the moment that you leave your house, but, again, you're not actually being paid by the clock. As long as no other law is being broken (and it appears from your telling that there isn't), then the employer can set any policy for how to compute the compensation that he wants. Regarding taxes, the employer probably has no discretion there. You're making what you're making, and the employer needs to tax it in total. Since you're driving a company vehicle from home, I don't think that you're entitled to any reimbursement (vs. wages) that would not be taxed unless maybe you pay for gas yourself. The gas money, if applicable, should be reimbursable as a business expense and that generally would not be taxed.\"",
"title": ""
}
] |
[
{
"docid": "494583",
"text": "\"The big difference is that you get your money earlier at the start. Suppose you start on a random day with payday on the last day of the month (monthly), or on every 2nd wednesday (biweekly), and it takes 3 days for payroll to \"\"ramp up\"\" (ie, if payday is within 3 days on your start date, your next paycheck is not on the next payday, but on the one after). If we assume every month has 30 days (to keep things simple), it is an average of 4+5+...+33 days until you get your first paycheck with monthly pay, an average of 18.5 days. For weekly it is a bit trickier Assuming you get hired at a random date here, with * being a paydate: time until you get paid: an average of 10.5 days. So you get your first pay an average of 8 days earlier. Later on, that 3 day thing no longer occurs, and now the company holds an average of 6.5 days of your pay \"\"due to you\"\" with biweekly paychecks, and about 14.5 days with weekly paychecks if you have monthly pay. So with monthly pay, on average your bank account has 8 fewer days of your pay in it at all times. This happens when you are first hired, and persists over the length of your employment. Now suppose you save that extra money (on average): Suppose you have an investment at 4% (after inflation). Over 40 years those 8 days of pay invested at 4% grow to 38 days of pay, a free month. What more, if the company has problems making payroll, you'll get a warning (to, say, look for another job) an average of 8 days sooner, and/or have the money in your account. Having someone owe you money is usually worse than having the money in your bank account.\"",
"title": ""
},
{
"docid": "457795",
"text": "The typical deal is you can put 10% of your gross pay into the ESPP. The purchase will occur on the last deposit date, usually a 6 month period, at a 15% discount to the market price. So, the math is something like this: Your return if sold the day it's purchased is not 15%, it's 100/85 or 17.6%. Minor nitpick on my part, I suppose. Also the return is not a 6 month return, as the weekly or bi-weekly deductions are the average between the oldest (6 mo) and the most recent (uh, zero time, maybe a week.) This is closer to 3 months. The annualized rate is actually pretty meaningless since you don't have 4 opportunities to achieve this return, it's important only if the cash flow hit causes you to borrow to support the ESPP purchases. The risk is whether the stock drops the 15% before you can execute the sell to take advantage of the gain. Of course the return is gross, you need to net for taxes. Edit to respond to comment below - When I said meaningless, I meant that you can't take the 17.6%, annualize it to 91.2% per year and think your $1000 will compound to $1912. It's as meaningless as when an investor gets a 10% gain on a stock in one day, and (with 250 trading days per year) decides his $1000 will be worth $2 quadrillion dollars after a year. The 17.6% is significant in that it's available twice per year, for a true 38% return over a year, but if borrowing to help the cash flow, that rate is really over 3 months.",
"title": ""
},
{
"docid": "175951",
"text": "Unfortunately, the tax system in the U.S. is probably more complicated than it looks to you right now. First, you need to understand that there will be taxes withheld from your paycheck, but the amount that they withhold is simply a guess. You might pay too much or too little tax during the year. After the year is over, you'll send in a tax return form that calculates the correct tax amount. If you have paid too little over the year, you'll have to send in the rest, but if you've paid too much, you'll get a refund. There are complicated formulas on how much tax the employer withholds from your paycheck, but in general, if you don't have extra income elsewhere that you need to pay tax on, you'll probably be close to breaking even at tax time. When you get your paycheck, the first thing that will be taken off is FICA, also called Social Security, Medicare, or the Payroll tax. This is a fixed 7.65% that is taken off the gross salary. It is not refundable and is not affected by any allowances or deductions, and does not come in to play at all on your tax return form. There are optional employee benefits that you might need to pay a portion of if you are going to take advantage of them, such as health insurance or retirement savings. Some of these deductions are paid with before-tax money, and some are paid with after tax money. The employer will calculate how much money they are supposed to withhold for federal and state taxes (yes, California has an income tax), and the rest is yours. At tax time, the employer will give you a form W-2, which shows you the amount of your gross income after all the before-tax deductions are taken out (which is what you use to calculate your tax). The form also shows you how much tax you have paid during the year. Form 1040 is the tax return that you use to calculate your correct tax for the year. You start with the gross income amount from the W-2, and the first thing you do is add in any income that you didn't get a W-2 for (such as interest or investment income) and subtract any deductions that you might have that are not taxable, but were not paid through your paycheck (such as moving expenses, student loan interest, tuition, etc.) The result is called your adjusted gross income. Next, you take off the deductions not covered in the above section (property tax, home mortgage interest, charitable giving, etc.). You can either take the standard deduction ($6,300 if you are single), or if you have more deductions in this category than that, you can itemize your deductions and declare the correct amount. After that, you subtract more for exemptions. You can claim yourself as an exemption unless you are considered a dependent of someone else and they are claiming you as a dependent. If you claim yourself, you take off another $4,000 from your income. What you are left with is your taxable income for the year. This is the amount you would use to calculate your tax based on the bracket table you found. California has an income tax, and just like the federal tax, some state taxes will be deducted from your paycheck, and you'll need to fill out a state tax return form after the year is over to calculate the correct state tax and either request a refund or pay the remainder of the tax. I don't have any experience with the California income tax, but there are details on the rates on this page from the State of California.",
"title": ""
},
{
"docid": "268294",
"text": "\"If they directly paid for your education, it is possible that it wouldn't count as taxable income to you according to the IRS, depending on the amount: If you receive educational assistance benefits from your employer under an educational assistance program, you can exclude up to $5,250 of those benefits each year. This means your employer should not include those benefits with your wages, tips, and other compensation shown in box 1 of your Form W-2. This also means that you do not have to include the benefits on your income tax return. source: http://www.irs.gov/publications/p970/ch11.html However, your situation is a bit trickier since they are sort of retroactively paying for your education. I'd think the answer is \"\"Maybe\"\" and you should consult a tax professional since it is a gray area. Update: On further research, I'm going to downgrade that \"\"Maybe\"\" to \"\"Probably not, but hopefully soon.\"\" The reason I am doing so is that there is a bill in Congress specifically to allow what you are asking, which presumes that you currently can't do this. The Bill is HR Bill 395 \"\"The Student Loan Employment Benefits Act of 2013\"\" sponsored by rep Steve Israel (D). It has co-sponsors from both parties, so that is promising for it's passage, I suppose. However, it appears to be still early in the legislative process. If this issue is near/dear to your heart maybe you should call your congressman. Summary of the Bill: (from govtrack.us) Student Loan Employment Benefits Act of 2013 - Amends the Internal Revenue Code to exclude from the gross income of an employee amounts paid by an employer under a student loan payment assistance program. Limits the amount of such exclusion to $5,000 in a taxable year. Requires an employer student loan payment assistance program to be a separate written plan of an employer to provide employees with student loan payment assistance. Defines \"\"student loan payment assistance\"\" as the payment of principal or interest on any indebtedness incurred by an employee solely to pay qualified higher education expenses which are paid or incurred within a reasonable time before or after such indebtedness was incurred and are attributable to education furnished during a period in which such employee was a student eligible for federal financial assistance.\"",
"title": ""
},
{
"docid": "529543",
"text": "\"I may be missing something here, but I don't think this is a disadvantage. The fact that the employer contribution will be taxed is the same as it would be if it were a match in a traditional account, so the amount you lose to taxes on it is a wash. The employer contribution is only smaller if you can't afford to contribute as much to the Roth because it's post-tax, and therefore your contribution is under the cap for the match. If you're contributing the maximum the employer will match or higher, then I don't think there's any disadvantage on the match portion. First, the 5% cap on employer contributions is calculated on the gross, even in a Roth account. Second, the taxing of the amount contributed to a Roth does not reduce the dollar amount that goes into the Roth account, it just reduces your net pay. So if your contribution is $100 to a Traditional account, your gross pay is reduced by $100 and your Traditional account gains $100. In the Roth, your gross pay is still taxed as though that $100 were included, but the $100 is put into the Roth. The tax portion of that \"\"after tax\"\" money does not reduce the amount of the contribution.\"",
"title": ""
},
{
"docid": "598899",
"text": "How will your employer treat your pay and benefits status while you're on leave? Disability income coverage and leave policies work in tandem to solve very different problems. Disability income coverage covers your income, leave policies guarantee your status as an employee. Typically, STD coverage requires an actual loss of income and will offset it's stated benefit for any income you're receiving. In general you can't begin a STD claim after the 7 day waiting period and also draw income from vacation or sick time. Also, typically STD will cover some percentage of your covered pay (sometimes including commission/bonus income) up to some weekly maximum. FLMA requires employers to allow certain amounts of time for certain types of leave. FMLA is not necessarily an income replacement tool like STD coverage. Contrary to your post it's my understanding that if sick and vacation time accrue in to a single PTO bucket your employer is prohibited from requiring employees to exhaust accrued time prior to beginning FMLA leave. In general, you're not missing anything because the point of FMLA is to guarantee your job and status as an employee from a benefits perspective. Benefits language from the Department of Labor Website A covered employer is required to maintain group health insurance coverage, including family coverage, for an employee on FMLA leave on the same terms as if the employee continued to work.",
"title": ""
},
{
"docid": "91466",
"text": "\"Gifts given and received between business partners or employers/employees are treated as income, if they are beyond minimal value. If your boss gives you a gift, s/he should include it as part of your taxable wages for payroll purposes - which means that some of your wages should be withheld to cover income, social security, and Medicare taxes on it. At the end of the year, the value of the gift should be included in Box 1 (wages) of your form W-2. Assuming that's the case, you don't need to do anything special. A 1099-MISC would not be appropriate because you are an employee of your boss - so the two of you need to address the full panoply of employment taxes, not just income tax, which would be the result if the payment were reported on 1099-MISC. If the employer wants to cover the cost to you of the taxes on the gift, they'll need to \"\"gross up\"\" your pay to cover it. Let's say your employer gives you a gift worth $100, and you're in a 25% tax bracket. Your employer has to give you $125 so that you end up with a gain of $100. But the extra $25 is taxable, too, so your employer will need to add on an extra $6.25 to cover the 25% tax on the $25. But, wait, now we've gotta pay 25% tax on the $6.25, so they add an extra $1.56 to cover that tax. And now they've gotta pay an extra $.39 . . . The formula to calculate the gross-up amount is: where [TAX RATE] is the tax rate expressed as a percentage. So, to get the grossed-up amount for a $100 gift in a 25% bracket, we'd calculate 1/(1-.25), or 1/.75, or 1.333, multiply that by the target gift amount of $100, and end up with $133.33. The equation is a little uglier if you have to pay state income taxes that are deductible on the federal return but it's a similar principle. The entire $133.33 would then be reported as income, but the net effect on the employee is that they're $100 richer after taxes. The \"\"gross-up\"\" idea can be quite complicated if you dig into the details - there are some circumstances where an additional few dollars of income can have an unexpected impact on a tax return, in a fashion not obvious from looking at the tax table. If the employer doesn't include the gift in Box 1 on the W-2 but you want to pay taxes on it anyway, include the amount in Line 7 on the 1040 as if it had been on a W-2, and fill out form 8919 to calculate the FICA taxes that should have been withheld.\"",
"title": ""
},
{
"docid": "463892",
"text": "Your employer's matching contribution is calculated based on the dollar amounts you end up putting in. The nature of your 401(k) contribution—whether pre-tax or Roth after-tax—doesn't matter with respect to how their match gets calculated, and their match always goes into a pre-tax account, even if you are contributing after-tax. The onus is on you to choose a contribution amount that maximizes your employer match regardless of the nature of your contribution. Maximizing your employer match using Roth after-tax contributions will eat up more of your annual gross salary, but as long as you are willing to do that then you won't leave free employer match money on the table. Roth after-tax contributions don't get the tax deduction inherent in a pre-tax contribution. The tradeoff is that you end up with less take-home pay per period if you contribute the same number of dollars on a Roth after-tax basis to your 401(k) as opposed to on a pre-tax basis. For instance, to make a maximum $18,000 Roth after-tax contribution to a 401(k), it's going to cost you a lot more than $18,000 of your annual gross salary to net the same $18,000 number. (On the flip side, the Roth money is worth more in retirement than pre-tax money, because it won't be subject to taxes then.) However, 401(k) plan contribution amounts are almost always expressed as a percentage of gross salary, i.e. in pre-tax terms, even when electing to make after-tax contributions! So when electing after-tax, one is implicitly accepting that the contribution will cost more than the percentage of gross salary, because you'll need to pay the tax on a gross amount that would yield the same number of dollars but as an after-tax amount.",
"title": ""
},
{
"docid": "42999",
"text": "After reading OP Mark's question and the various answers carefully and also looking over some old pay stubs of mine, I am beginning to wonder if he is mis-reading his pay stub or slip of paper attached to the reimbursement check for the item(s) he purchases. Pay stubs (whether paper documents attached to checks or things received in one's company mailbox or available for downloading from a company web site while the money is deposited electronically into the employee's checking account) vary from company to company, but a reasonably well-designed stub would likely have categories such as Taxable gross income for the pay period: This is the amount from which payroll taxes (Federal and State income tax, Social Security and Medicare tax) are deducted as well as other post-tax deductions such as money going to purchase of US Savings Bonds, contributions to United Way via payroll deduction, contribution to Roth 401k etc. Employer-paid group life insurance premiums are taxable income too for any portion of the policy that exceeds $50K. In some cases, these appear as a lump sum on the last pay stub for the year. Nontaxable gross income for the pay period: This would be sum total of the amounts contributed to nonRoth 401k plans, employee's share of group health-care insurance premiums for employee and/or employee's family, money deposited into FSA accounts, etc. Net pay: This is the amount of the attached check or money sent via ACH to the employee's bank account. Year-to-date amounts: These just tell the employee what has been earned/paid/withheld to date in the various categories. Now, OP Mark said My company does not tax the reimbursement but they do add it to my running gross earnings total for the year. So, the question is whether the amount of the reimbursement is included in the Year-to-date amount of Taxable Income. If YTD Taxable Income does not include the reimbursement amount, then the the OP's question and the answers and comments are moot; unless the company has really-messed-up (Pat. Pending) payroll software that does weird things, the amount on the W2 form will be whatever is shown as YTD Taxable Income on the last pay stub of the year, and, as @DJClayworth noted cogently, it is what will appear on the W2 form that really matters. In summary, it is good that OP Mark is taking the time to investigate the matter of the reimbursements appearing in Total Gross Income, but if the amounts are not appearing in the YTD Taxable Income, his Payroll Office may just reassure him that they have good software and that what the YTD Taxable Income says on the last pay stub is what will be appearing on his W2 form. I am fairly confident that this is what will be the resolution of the matter because if the amount of the reimbursement was included in Taxable Income during that pay period and no tax was withheld, then the employer has a problem with Social Security and Medicare tax underwithholding, and nonpayment of this tax plus the employer's share to the US Treasury in timely fashion. The IRS takes an extremely dim view of such shenanigans and most employers are unlikely to take the risk.",
"title": ""
},
{
"docid": "307120",
"text": "\"Unemployment insurance provides a temporary safety net to workers who lose their jobs by replacing a portion of their salary for certain periods. Each state administers its own unemployment insurance program so some rules may vary from state to state. To receive unemployment insurance payments, you must have lost your job through no fault of your own. If you quit your job or lost it because of poor performance or another justifiable reason, you are not eligible for unemployment insurance benefits. State unemployment insurance programs require claimants to have worked sufficiently before they can claim benefits. As soon as you apply for unemployment insurance, an agency with the state in which you live will verify that you were a victim of a layoff by contacting your previous employer and making sure you lost your job due to lack of work and not an action within your control. After the state verifies you were indeed the victim of a layoff, your weekly payment is calculated. Your payment will be a percentage of what you made in your previous job, generally between 20 percent and 50 percent, depending on your state. Unemployment insurance replaces only a portion of your previous pay because it is intended to pay only for the essentials of living such as food and utilities until you find new employment. Before you begin receiving benefits, you must complete a waiting period of typically one or two weeks. If you find a new job during this period, you will not be eligible for unemployment benefits, even if the job does not pay you as much as your previous job. After the waiting period, you will begin to receive your weekly payments. Employers pay for unemployment insurance through payroll taxes. So, while employees' work and earnings history are important to funding their unemployment benefits, the money does not come from their pay. Employer unemployment insurance contributions depend on several factors, including how many former employees have received benefits. Employers pay taxes on an employee's base wages, which vary by state. California, for example taxes employers on the first $7,000 of an employee's annual earnings, while neighboring Oregon taxes up to $32,000 of wages. Employers must set aside funds each payroll period and then report taxes and pay their states quarterly. States have several categories of tax rates they charge employers. New businesses and those first adding employees pay the \"\"new rate,\"\" which is typically lower and geared toward small businesses. Established businesses who haven't paid their taxes recently or properly are usually assessed the \"\"standard rate\"\" --- the highest possible tax rate, which in 2010 ranged from 5.4 percent in several states including Georgia, Hawaii and Alaska to 13.56 percent in Pennsylvania. Businesses in good standing may receive discounts under the \"\"experienced rate.\"\" Depending on the number of employees a business has and how many former employees have claimed unemployment, states can give sizable rate reductions. The fewer claims, the lower the rate a business pays in unemployment insurance taxes. As a result of the economic crisis legislation has been passed to extend Unemployment benefits. Regular unemployment benefits are paid for a maximum of 26 weeks in most states. However, additional weeks of extended unemployment benefits are available during times of high unemployment. The unemployment extension legislation passed by Congress in February 2012 changed the way the tiers of Emergency Unemployment Compensation (EUC) are structured. A tier of unemployment is an extension of a certain amount of weeks of unemployment benefits. There are currently four tiers of unemployment benefits. Each tier provides extra weeks of unemployment in addition to basic state unemployment benefits. Emergency Unemployment Compensation (EUC) Tiers June - August 2012: Source and further information can be found here - Unemployment Tiers - About.com Sources: Unemployment Insurance(UI) - US Dept. of Labor How Does Unemployment Insurance Work? - eHow Percentage of Pay That Goes to Unemployment Insurance - eHow Additional Info: You can file for UI over the internet here are some useful resources. OWS Links State Unemployment Offices - About.com How to Apply for Unemployment Over the Internet - eHow\"",
"title": ""
},
{
"docid": "304933",
"text": "Gross pay is the total your employer is paying you. Net pay is the amount of money you actually received (should match your check or direct deposit), which is gross pay minus deductions (healthcare, 401k contributions, commuter tax-free programs, etc), taxes (as explained already), 401k loan repayments, garnishments (child support, IRS messes, etc).",
"title": ""
},
{
"docid": "367026",
"text": "Should I have a W-2 re-issued? A W-2 can be corrected and a new copy will be filed with the IRS if your employer incorrectly reported your income and withholding on a W-2 that they issued. In this case, though the employer didn't withhold those taxes, they should not reissue the W-2 unless they plan to pay your portion of the payroll taxes that were not withheld. (If they paid your share of the taxes, that would increase your gross income.) Who pays for the FICA I should have paid last year? Both you and your employer owe 7.65% each for FICA taxes. By law your employer is required to pay their half and you are required to pay your half. Both you and your employer owe additional taxes because of this mistake. Your other questions assume that your employer will pay your portion of the taxes withheld. You employer could decide to do that, but this also assumes that it was your employer's fault that the mistakes were made. If you transitioned to resident alien but did not inform your employer, how is that your employer's fault?",
"title": ""
},
{
"docid": "240259",
"text": "401k contributions are exempt from employee and employer FICA withholding. The employer withholding is approximately 7% of the gross. The closer the employer match ratio is to 7%, the closer it is to paying for itself. Example: Assuming an employee is match-maximizing and in very round numbers grosses 100,000 per year. A 50% match schedule is about $350 cheaper per employee than a 100% match schedule: Default non participant: The employee will see about 7000 deducted for FICA, and the employer will pay 7000 to FICA if they don't participate. First case: the match is 100%, 1-for-1 to a 5% cap, the employee will deduct 5000, and have 6650 withheld for FICA. The employer will pay 6650 to FICA. The total employer cost of withholding and match is 11,650. Second case: If the match is 50%, 1-for-2 to a 5% cap, the employee will deduct 10000, and have 6300 withheld for FICA. The employer will pay 6300 to FICA. The total employer cost of withholding and match is 11,300.",
"title": ""
},
{
"docid": "223170",
"text": "Since your YouTube income is considered self-employment income and because you probably already made more than $400 in net income (after deducting expenses from the $4000 you've received so far), you will have to pay self-employment tax and file a return. This is according to the IRS's Publication 17 (2016), Your Federal Income Tax, so assumes the same rules for 2016 will remain in effect for 2017: You are self-employed if you: Carry on a trade or business as a sole proprietor, Are an independent contractor, Are a member of a partnership, or Are in business for yourself in any other way. Self-employment can include work in addition to your regular full-time business activities, such as certain part-time work you do at home or in addition to your regular job. You must file a return if your gross income is at least as much as the filing requirement amount for your filing status and age (shown in Table 1-1). Also, you must file Form 1040 and Schedule SE (Form 1040), Self-Employment Tax, if: Your net earnings from self-employment (excluding church employee income) were $400 or more, or You had church employee income of $108.28 or more. (See Table 1-3.) Use Schedule SE (Form 1040) to figure your self-employment tax. Self-employment tax is comparable to the social security and Medicare tax withheld from an employee's wages. For more information about this tax, see Pub. 334, Tax Guide for Small Business. I'd also note that your predicted income is getting close to the level where you would need to pay Estimated Taxes, which for self-employed people work like the withholding taxes employers remove their employees paychecks and pay to the government. If you end up owing more than $1000 when you file your return you could be assessed penalties for not paying the Estimated Taxes. There is a grace period if you had to pay no taxes in the previous year (2016 in this case), that could let you escape those penalties.",
"title": ""
},
{
"docid": "535673",
"text": "From the Massachusetts Department of Revenue: 1st - Massachusetts Source Income That is Excluded Massachusetts gross income excludes certain items of income derived from sources within Massachusetts: non-business related interest, dividends and gains from the sale or exchange of intangibles, and qualified pension income. 2nd - Massachusetts Source Income That is Included: Massachusetts gross income includes items of income derived from sources within Massachusetts. This includes income: 3rd - Trade or business, Including Employment Carried on in Massachusetts: A nonresident has a trade or business, including any employment carried on in Massachusetts if: A nonresident generally is not engaged in a trade or business, including any employment carried on in Massachusetts if the nonresident's presence for business in Massachusetts is casual, isolated and inconsequential. A nonresident's presence for business in Massachusetts will ordinarily be considered casual, isolated and inconsequential if it meets the requirements of the Ancillary Activity Test (AAT) and Examples. When nonresidents earn or derive income from sources both within Massachusetts and elsewhere, and no exact determination can be made of the amount of Massachusetts source income, an apportionment of income must be made to determine that amount considered Massachusetts gross income. 4th - Apportionment of Income: Apportionment Methods: The three most common apportionment methods used to determine Massachusetts source income are as follows: Gross income is multiplied by a: So if you go to Massachusetts to work, you have to pay the tax. If you collect a share of the profit or revenue from Massachusetts, you have to pay tax on that. If you work from Oregon and are paid for that work, then you don't pay Massachusetts tax on that. If anything, your company might have to pay Oregon taxes on revenue you generate (you are their agent or employee in Oregon). Does the answer change depending on whether the income is reported at 1099 or W-2? This shouldn't matter legally. It's possible that it would be easier to see that the work was done in Oregon in one or the other. I.e. it doesn't make any legal difference but may make a practical difference. All this assumes that you are purely an employee or contractor and not an owner. If you are an owner, you have to pay taxes on any income from your Massachusetts business. Note that this applies to things like copyrights and real estate as well as the business. This also assumes that you are doing your work in Oregon. If you live in Oregon and travel to Massachusetts to work, you pay taxes on your Massachusetts income in Massachusetts.",
"title": ""
},
{
"docid": "361954",
"text": "Everyone pays their personal income tax with funds from their employer; some of it through withholding, and the rest through the balance due at the time of filing. All that is happening here is that the company is calculating your personal tax return for you, and fiddling retroactively with the gross salary to yield a specific after-tax salary. One problem is that there is a lot of information I put in my return to earn deductions, that I would not care to tell my employer. The system would also appear to be contrary to public policy. Governments create tax deductions to give a larger income to those with socially acceptable expenses: health care, dependents, etc. The system you describe would give employees with such deductions a lower gross salary.",
"title": ""
},
{
"docid": "99434",
"text": "\"I have an indirect answer for you. It is not a numeric answer but it is a procedure. The challenge with paying taxes for an employee besides their share of Social security and Medicare is that you have no idea what their state and Federal taxes are. Are they married, single, head of household? Is this their entire families income, or is it extra money to make ends meet? What about state taxes? It looks like you will need a W-4 from them. As you know the IRS Tax topic 756 has all the info you need. Federal Income Tax Withholding You are not required to withhold federal income tax from wages you pay to a household employee. However, if your employee asks you to withhold federal income tax and you agree, you will need a completed Form W-4 (PDF), Employee's Withholding Allowance Certificate from your employee. See Publication 15, (Circular E), Employer's Tax Guide, which has tax withholding tables that are updated each year. Form W-2, Wage and Tax Statement If you must withhold and pay Social Security and Medicare taxes, or if you withhold federal income tax, you will need to complete Form W-2 (PDF), Wage and Tax Statement, for each employee. You will also need a Form W-3 (PDF), Transmittal of Wage and Tax Statement. See \"\"What Forms Must You File?\"\" in Publication 926 (PDF) for information on when and where to furnish and file these forms. To complete Form W-2 you will need an employer identification number (EIN) and your employees' Social Security numbers. If you do not already have an EIN, you can apply for one using the online EIN application available on IRS.gov. This service is available Monday through Friday, 7 a.m. to 10 p.m. Eastern time. You can also apply for an EIN by mailing or faxing a completed Form SS-4 (PDF), Application for Employer Identification Number. International applicants may apply by calling 267-941-1099 (not a toll-free number) Monday through Friday, 6 a.m. to 11 p.m. Eastern time to obtain their EIN. Refer to Topics 752 and 755 for further information. Don't forget Federal Unemployment Tax. Pub 15 will have tables so you can determine how much you should have been withholding if you had gone that route. It will be easiest to use a spreadsheet to do the calculations so that what you gave them in their checks is their net pay not their gross. The tables are constructed under the assumption you know their gross pay.\"",
"title": ""
},
{
"docid": "280081",
"text": "\"In the U.S., virtually all salaries are expressed as \"\"gross salaries\"\", which are before the taxes that the individual must pay on their income. The numbers shown in the links are almost certainly gross salary figures. However, the \"\"gross salary\"\" is not the entire \"\"total compensation\"\" number, which is the total value of all compensation and benefits that the employee receives for his work. Total compensation includes not only salary and bonuses, but the cost or value of any employer-paid healthcare, retirement, company car, expense account, stock options, and other valuable goods or services. That's still not the total amount of money the company has to pay to have you; there are employer-paid payroll taxes totaling 6.2% of your gross salary, plus practical costs like the cost of your computer, cubicle or office furniture, and the portion of utility costs that keep you well-lit, clean and comfortable. This complete number is called \"\"total employee cost\"\", and the general rule of thumb is that it's double your gross cash compensation (salary + bonuses). Lastly, $100k in California isn't worth as much, in real terms, as $100k in other parts of the U.S. The cost of living in California, especially in Silicon Valley where the majority of the people who make six figures by being C++ programmers are located, is ridiculously expensive. There are other tech hubs in the U.S., like DFW, Austin TX, Atlanta GA, St Louis MO, Raleigh NC, etc where people earn less, but also spend less to live and so can use more of their salary in a \"\"discretionary\"\" manner.\"",
"title": ""
},
{
"docid": "424961",
"text": "I suggest taking a look at your pay stub or pay statement. Your employer should provide you with one for each time you get paid. This shows your gross income (pay period and year to date or YTD for short) and all stuff that gets deducted and how your actual payment is calculated. In my case there are nine things that get taken off: Other things that might show up there are various life or accident insurances, Child Care flexible spending account, legal & pet insurances, long term disability, etc. Some of those are under your control (through benefit election or contribution choices), others you just have to live with. Still, it's worth spending the time to look at it occasionally.",
"title": ""
},
{
"docid": "136804",
"text": "Technically you owe 'self-employment' taxes not FICA taxes because they are imposed under a different law, SECA. However, since SE taxes are by design exactly the same rates as combining the two halves of FICA (employer and employee) it is quite reasonable to treat them as equivalent. SE taxes (and income tax also) are based on your net self-employment income, after deducting business expenses (but not non-business items like your home mortgage, dependent exemptions, etc which factor only into income tax). You owe SE Medicare tax 2.9% on all your SE net income (unless it is under $400) adjusted down by 7.65% to compensate for the fact that the employer half of FICA is excluded from gross income before the employee half is computed. You owe SE Social Security tax 12.4% on your adjusted SE net income unless and until the total income subject to FICA+SECA, i.e. your W-2 wages plus your adjusted SE net income, exceeds a cap that varies with inflation and is $127,200 for 2017. OTOH if FICA+SECA income exceeds $200k single or $250k joint you owe Additional Medicare tax 0.9% on the excess; if your W-2 income (alone) exceeds this limit your employer should withhold for it. However the Additional Medicare tax is part of 'Obamacare' (PPACA) which the new President and Republican majorities have said they will 'repeal and replace'; whether any such replacement will affect this for TY 2017 is at best uncertain at this point. Yes SE taxes are added to income tax on your 1040 with schedule SE attached (and schedule C/CEZ, E, F as applicable to your business) (virtually so if you file electronically) and paid together. You are supposed to pay at least 90% during the year by having withholding increased on your W-2 job, or by making 'quarterly' estimated payments (IRS quarters are not exactly quarters, but close), or any combination. But if this is your first year (which you don't say, but someone who had gone through this before probably wouldn't ask) you may get away with not paying during the year as normally required; specifically, if your W-2 withholding is not enough to cover your increased taxes for this year (because of the additional income and SE taxes) but it is enough to cover your tax for the previous year and your AGI that year wasn't over $150k, then there is a 'safe harbor' and you won't owe any form-2210 penalty -- although you must keep enough money on hand to pay the tax by April 15. But for your second year and onwards, your previous year now includes SE amounts and this doesn't help. Similar/related:",
"title": ""
},
{
"docid": "214358",
"text": "Here is a quote from the IRS website on this topic: You may be able to deduct premiums paid for medical and dental insurance and qualified long-term care insurance for yourself, your spouse, and your dependents. The insurance can also cover your child who was under age 27 at the end of 2011, even if the child was not your dependent. A child includes your son, daughter, stepchild, adopted child, or foster child. A foster child is any child placed with you by an authorized placement agency or by judgment, decree, or other order of any court of competent jurisdiction. One of the following statements must be true. You were self-employed and had a net profit for the year reported on Schedule C (Form 1040), Profit or Loss From Business; Schedule C-EZ (Form 1040), Net Profit From Business; or Schedule F (Form 1040), Profit or Loss From Farming. You were a partner with net earnings from self-employment for the year reported on Schedule K-1 (Form 1065), Partner's Share of Income, Deductions, Credits, etc., box 14, code A. You used one of the optional methods to figure your net earnings from self-employment on Schedule SE. You received wages in 2011 from an S corporation in which you were a more-than-2% shareholder. Health insurance premiums paid or reimbursed by the S corporation are shown as wages on Form W-2, Wage and Tax Statement. The insurance plan must be established, or considered to be established as discussed in the following bullets, under your business. For self-employed individuals filing a Schedule C, C-EZ, or F, a policy can be either in the name of the business or in the name of the individual. For partners, a policy can be either in the name of the partnership or in the name of the partner. You can either pay the premiums yourself or your partnership can pay them and report the premium amounts on Schedule K-1 (Form 1065) as guaranteed payments to be included in your gross income. However, if the policy is in your name and you pay the premiums yourself, the partnership must reimburse you and report the premium amounts on Schedule K-1 (Form 1065) as guaranteed payments to be included in your gross income. Otherwise, the insurance plan will not be considered to be established under your business. For more-than-2% shareholders, a policy can be either in the name of the S corporation or in the name of the shareholder. You can either pay the premiums yourself or your S corporation can pay them and report the premium amounts on Form W-2 as wages to be included in your gross income. However, if the policy is in your name and you pay the premiums yourself, the S corporation must reimburse you and report the premium amounts on Form W-2 as wages to be included in your gross income. Otherwise, the insurance plan will not be considered to be established under your business. Medicare premiums you voluntarily pay to obtain insurance in your name that is similar to qualifying private health insurance can be used to figure the deduction. If you previously filed returns without using Medicare premiums to figure the deduction, you can file timely amended returns to refigure the deduction. For more information, see Form 1040X, Amended U.S. Individual Income Tax Return. Amounts paid for health insurance coverage from retirement plan distributions that were nontaxable because you are a retired public safety officer cannot be used to figure the deduction. Take the deduction on Form 1040, line 29.",
"title": ""
},
{
"docid": "214009",
"text": "I have a very hard time believing you pay 60% of gross. Otherwise, I believe you're right in the way this works: Suppose you make $100k and pay 25% of that in taxes. 100,000 * .25 = 25,000 But if you spend $1,000 pretax, then it's as if you were paid $99,000 99,000 * .25 = $24,750 So the difference is $250. Which is the same as that $1,000 * .25.",
"title": ""
},
{
"docid": "599835",
"text": "For 2014/15 it looks something like this: To make it a bit clearer, let's also plot the difference in net income for self-employment and a single person company compared to employment: Self-employment is slightly worse between £5885 and about £10,500 because Class 2 NI kicks in before the employed person starts paying any tax. After that, self-employment is better because you pay 9% Class 4 NI rather than 12% Class 1 NI. Once higher rate tax kicks in, the saving stops growing. The single-person company is most tax-efficient at all points, ignoring any accountancy costs it incurs. Strange things happen between £100k and about £135k because the withdrawal of the personal allowance kicks in at a different point when receiving dividends. We can also plot the percentage of income paid as tax for each case: The strange kink for self-employment below £10k is caused by Class 2 NI again. Employment and self-employment both gradually tend towards paying 47%, reaching 46.5% for £2m gross income. The company tends towards 44.44%, reaching 43.6% for £2m gross income.",
"title": ""
},
{
"docid": "477476",
"text": "Welcome to the wonderful but oft confusing world of self-employment. Your regular job will withhold income for you and give you a W2, which tells you and the government how much is withheld. At the end of the year uber will give you and the government a 1099-misc, which will tell you how much they paid you, but nothing will be withheld, which means you will owe the government some taxes. When it comes to taxes, you will file a 1040 (the big one, not a 1040EZ nor 1040A). In addition you will file a schedule C (self-employed income), where you will report the gross paid to you, deduct your expenses, and come up with your profit, which will be taxable. That profit goes into a line in the 1040. You need to file schedule SE. This says how much self-employment tax you will pay on your 1099 income, and it will be more than you expect. Self employment tax is SS/Medicare. There's a line for this on the 1040 as well. You can also deduct half of your self-employment tax on the 1040, there's a line for it. Now, you can pay quarterly taxes on your 1099 income by filing 1040-ES. That avoids a penalty (which usually isn't that large) for not withholding enough. As an alternative, you can have your regular W2 job withhold extra. As long as you don't owe a bunch at tax time, you won't be a fined. When you are self-employed your taxes aren't as simple. Sorry. You can either spend some time becoming an expert by studying the instructions for the 1040, pay for the expensive version of tax programs, or hire someone to do it for you. Self-employed taxes are painful, but take advantage of the upsides as well. You can start a solo 401(k) or SEP IRA, for example. Make sure you are careful to deduct every relevant business expense and keep good records in case you get audited.",
"title": ""
},
{
"docid": "573265",
"text": "The are a couple of explanations that I can think of; though for determining exactly what is different you will want to print out both returns and compare them line by line to see how they differ. If the company grossed up your income to account for the taxes on housing (possibly by paying the additional withholding), you may be just benefiting from them estimating your tax rate. This can especially be the case if your only work was the three month internship. They would have to assume your salary was for the entire year. There is an earned income tax credit for low wage earners that you may have qualified for (it would depend your specific circumstances if you meet the criteria). But that credit for a range of income actually pays out more the more you earn (to encourage working that extra hour instead of reducing benefit because you had another hour of employment). As for the housing subsidy itself, while the value is quite high the IRS considers that to be a taxable benefit that the employer provided you and so it needs to be added to your W-2 wages. $8k a month seems quite high, but I don't know the quality of the apartment you were provided and what the going rates are in the area. Given that you said you worked for a major tech company, I can imagine that you might have been working in an area with high rents. If the employer did gross up your paycheck so as to cover your taxes, that $24k would also include that extra tax payment (e.g. if the employer paid $8k in additional taxes for you, then the housing cost that they directly paid were $16k).",
"title": ""
},
{
"docid": "530441",
"text": "There are a lot of moving parts, individual premiums and annual increases have little to do with employer premiums and annual increases and vice versa. Most people think of XYZ insurer as a single company with a single pool of insured folks. This common knowledge isn't accurate. Insurers pool their business segments separately. This means that Individual, small business, mid-size business, and large business are all different operating segments from the viewpoint of the insurer. It's possible to argue that because so many people are covered by employer plans that individual plans have a hard time accumulating the required critical mass of subscribers to keep increases reasonable. Age banded rating: Individual coverage and small group coverage is age rated, meaning every year you get older. In addition to your age increase, the premium table for your plan also receives an increase. Employers with 100+ eligible employees are composite rated (in general), meaning every employee costs the same amount. The 18 year old employee costs $500 per month, the 64 year old costs $500 per month. Generally, the contributions an employee pays to participate in the plan are also common among all ages. This means that on a micro level increases can be more incremental because the employer is abstracting the gross premium. Composite rating generally benefits older folks while age rating generally benefits younger folks. Employer Morale Incentive: Generally the cost to an employee covered by an employer plan isn't directly correlated to the gross premium, and increases to the contribution(s) aren't necessarily correlated to the increases the employer receives. Employers are incentivised by employee morale. It's pretty common for employers to shoulder a disproportionate amount of an increase to keep everyone happy. Employers may offset the increase by shopping some ancillary benefit like group life insurance, or bundling the dental program with the medical carrier. Remember, employees don't pay premiums they pay contributions and some employers are more generous than others. Employers are also better at budgeting for planned increases than individuals are. Regulators: In many of the states that are making the news because of their healthcare premium increases there simply isn't a regulator scrutinizing increases. California requires all individual and small group premiums to be filed with the state and increases must be justified with some sort of math and approved by a regulator. Without this kind of oversight insurers have only the risk of subscriber flight to adjust plan provisions and press harder during provider contract negotiations. Expiring Transitional Reinsurance Fee and Funds: One of the fees introduced by healthcare reform paid by insurers and self-insured employers established a pot of money that individual plans could tap to cope with the new costs of the previously uninsurable folks. This fee and corresponding pot of money is set to expire and can no longer be taken in to account by underwriters. Increased Treatment Availability: It's important that as new facilities go online, insurer costs will increase. If a little town gets a new cancer clinic, that pool will see more cancer treatment costs simply as a result of increased treatment availability. Consider that medical care inflation is running at about 4.9% annually as of the most recent CPI table, the rest of the increases will result from the performance of that specific risk pool. If that risk pool had a lot of cancer diagnoses, you're looking at a big increase. If that risk pool was under priced the prior year you will see an above average increase, etc.",
"title": ""
},
{
"docid": "137393",
"text": "\"As you clarified in the comments, it is not a contract work but rather an additional temporary assignment with the same employer. You were paid for it in form of a \"\"bonus\"\" - one time irregular payment, instead of regular periodic payments. Irregular wage payments fall under the flat rate withholding rule (the 25% for Federal, some States have similar rules for State withholding). This is not taxes, this is withholding. Withholding is money the employer takes from your salary and forwards to the IRS on the account of your tax liability, but it is not in itself your tax liability. When you do your annual tax return, you'll calculate the actual tax you were supposed to pay, and the difference between what was withheld and your actual tax will be refunded to you (or owed by you, if not enough was withheld). You can control the regular pay withholding using W4 form.\"",
"title": ""
},
{
"docid": "85954",
"text": "FSA is a convenience to allow you to pay day care expenses with pre-tax money. It sounds like neither you nor your wife are eligible through an employer, so you can't use one. If you do not use FSA, then at tax time you can deduct the cost of day care from your gross income. In the end the effect is the same. Just keep track of your expenses.",
"title": ""
},
{
"docid": "169312",
"text": "\"Evaluate if the Rs 5 million term insurance is sufficient. Typically the term insurance provided by employer is in the range of 1 to 3 times the gross. Generally one should be covered in the range of 5 to 10 times the Gross. The sooner you start the lesser the premium and you can get insured for a large amount for a long duration at very nominal rate. NOTE: You can also buy a health insurance for your father, note these typically come at high cost, generally if over 70 years of age, 25% is the premium amount and 25% as co-pay. So if your dad doesn't fall ill once in 3 years, its a loss making proposition. Edit: Accident insurance best take is along with rider on term plan. Additional Health insurance is a good idea and helps if you are in between jobs. Plus the new company health insurance can reject a particular treatment as \"\"Pre-Existing\"\". i.e. certain illness [in certain plans] require one to have coverage for 3 years before the claim for it can be covered.\"",
"title": ""
},
{
"docid": "279824",
"text": "Not really. You just pay the other side of payroll taxes your employer typically pays. That's 7.65% more on your net. Not that much, all things considered. Plus, on part time Uber driving, the depreciation deduction on a car should exceed true depreciation costs. Putting 10K more miles on a car each year does not result in that much extra depreciation. 2010 Honda Civic DX Sedan 4D with 100K miles is worth $4,500 in Good condition, according to KBB. With 130K miles, it's worth $3,900. That's a difference of $600, or $0.02 per mile. You'll have more oil changes, brake replacements, gas, and other operating costs. But depreciation is small potatoes compared to the $0.535 in deductions per mile. Edit: If you would own a car regardless of whether or not you drive for Uber, Uber isn't a bad deal. It's a bad deal if you have to buy a car just to drive for Uber. It's all about the marginal cost of a mile.",
"title": ""
}
] |
2290
|
For Federal Crimes, where does the money collected from penalties go?
|
[
{
"docid": "46145",
"text": "\"The SFGate had an article on this a few years ago: http://www.sfgate.com/business/networth/article/When-government-fines-companies-who-gets-cash-3189724.php \"\"Civil penalties, often referred to as fines, usually go to the U.S. Treasury or victims.\"\" Short answer in the case you references it would be the US Treasury. In cases where there is a harmed party then they would get something to account for their loss. But it can get complicated depending on the crime.\"",
"title": ""
}
] |
[
{
"docid": "10089",
"text": "Congratulations on deciding to save for retirement. Since you cite Dave Ramsey as the source of your 15% number, what does he have to say about where to invest the money? If you want to have instantaneous penalty-free access to your retirement money, all you need to do is set up one or more ordinary accounts that you think of as your retirement money. Just be careful not to put the money into CDs since Federal law requires a penalty of three months interest if you cash in the CD before its maturity date (penalty!) or put the money into those pesky mutual funds that charge a redemption fee (penalty!) if you take the money out within x months of investing it where x can be anywhere from 3 to 24 or more. In Federal tax law (and in most state tax laws as well) a retirement account has special privileges accorded to it in that the interest, dividends, capital gains, etc earned on the money in your retirement account are not taxed in the year earned (as they would be in a non-retirement account), but the tax is either deferred till you withdraw money from the account (Traditional IRAs, 401ks etc) or is waived completely (Roth IRAs, Roth 401ks etc). In return for this special treatment, penalties are imposed (in addition to tax) if you withdraw money from your retirement account before age 59.5 which presumably is on the distant horizon for you. (There are some exceptions (including first-time home buying and extraordinary medical expenses) to this rule that I won't bother going into). But You are not required to invest your retirement money into such a specially privileged retirement account. It is perfectly legal to keep your retirement money in an ordinary savings account if you wish, and pay taxes on the interest each year. You can invest your retirement money into municipal bonds whose interest is free of Federal tax (and usually free of state tax as well if the municipality is located in your state of residence) if you like. You can keep your retirement money in a sock under your mattress if you like, or buy a collectible item (e.g. a painting) with it (this is not permitted in an IRA), etc. In short, if you are concerned about the penalties imposed by retirement accounts on early withdrawals, forgo the benefits of these accounts and put your retirement money elsewhere where there is no penalty for instant access. If you use a money management program such as Mint or Quicken, all you need to do is name one or more accounts or a portfolio as MyRetirementMoney and voila, it is done. But those accounts/portfolios don't have to be retirement accounts in the sense of tax law; they can be anything at all.",
"title": ""
},
{
"docid": "344165",
"text": "\"Banks use the money for productive pursuits, earning returns in excess of what they will owe the fed in discount interest. If a bank could not yield a return greater than their interest due their lender (whether that lender is the fed or not) they probably wouldn't borrow in the first place. EDIT: I misunderstood the question. The federal reserve does not disseminate new money by making loans. They do so by issuing and trading in bonds. The US Treasury, for example, issues a bond. The Federal Reserve Bank buys this bond using money they \"\"printed\"\". So the same question applies.... where does the money come from to pay the interest on the bond? It comes from the perpetual issuance and trading in bonds at a growing rate. All the fed needs to do is to buy bonds at a rate faster than they collect interest.\"",
"title": ""
},
{
"docid": "286992",
"text": "\"Is there a solution here that would allow me to provide him with a debit card in his name that I could fund, that wouldn't have foreign transaction fees associated with it (I'd probably be okay with a small fixed ATM fee). There are separate issues here. There is no law limiting bank accounts to U.S. citizens, but most banks will not open an account for a non-citizen outside their declared service area. There are substantial legal liabilities to the bank in allowing it, whether a citizen or non-citizen. The difficulty will be compliance with the Patriot Act. This is an extension of the older \"\"Know Your Customer\"\" doctrine. It is improbable that the bank could comply with the Act without the potential customer being physically present. You would have to check with your bank in advance as to their policies. Banks are not required to accept a customer outside their policies. As to waiving the foreign transaction fee, that is very improbable. Although a handful of institutions do this in specific cases it is uncommon because the bank isn't actually charging the fee, they are passing it along. With a credit card they collect interest and waiving the fee can be thought of as a reduction in interest income, that isn't possible on a debit card. You would want to make sure you have a scrupulously honest nephew. You could be held criminally liable for any actions he takes at both the state and the federal level. U.S. law is global. A citizen who commits a crime in any country of the world can be charged for it in the United States. By being on the account you can acquire any liabilities that are created as an accomplice. This is a bigger issue at the federal level because 4,000 federal laws do not require criminal intent. Some do not require you to even know the action happened. Unlike state law which generally requires you intended to commit a crime and had to be aware of it, federal law often does not. It is also not adequate that the action is legal in Russia if it would be illegal in the United States. If I get a card in my name, and give it to him to use to withdraw money from ATMs, is that legal? What problems might that cause? It is legal, but you are now strictly liable for its use. See the above answer. It would probably get shut down anyway when they phone you and asked: \"\"are you in Russia right now?\"\" The bank is still liable for you giving away the card. The bank may close out all your accounts and submit a currency transaction report on you to the Treasury for possible money laundering. Wire the money. Plan out how much and when, but just wire it.\"",
"title": ""
},
{
"docid": "480238",
"text": "They can go to an ATM and deposit it in to their account. The ATM does not care to read the name, and the bank does not care to verify anything if the check goes through (meaning the bank it is drawn on pays). So if nobody complains, that's it, he has your money. You would need to go to the check-writer's bank and ask for help, or look at the check-writer's cancelled check copy if you get to it. That bank can find out where it was deposited to, and then you have to go after the guy and get your money back - if it is still recoverable! - if it is a poor sod and he already blew your 5 grand, you can sue his pants off, but there are no 5 grand in them anywhere. So bad luck for you. Technically, the bank is not supposed to accept the check if the name doesn't match. At the counter, that might get a question, but as said above, there are deposit ATMs, and he could also just endorse the check to himself and sign the endorsement with some illegible scrawling, and claim that this is your signature - how would Joe the teller know? Either way, he gets the check in his account, and then he can take it out and blow it. It is legally clearly theft or fraud, and probably a federal crime, but if the guy is bankrupt, that doesn't help you much. Depending on that bank's fine-print, they might or might not cover your loss, but I wouldn't hold my breath. Better don't lose a check.",
"title": ""
},
{
"docid": "216274",
"text": "\"Every year, you save your receipts, track your expenses and - when April comes around - pay your taxes. But what if you know of someone who isn't as honest as you are? Someone who skims on their income or misreports information in order to be placed in a lower bracket. The Internal Revenue Service (IRS) estimates that Americans underpay their [taxes](http://www.investopedia.com/articles/taxes/09/reporting-tax-cheats.asp) by about $345 billion every year, according to Barron's, the popular financial news website and magazine. In fiscal 2009, the IRS collected $48.9 billion in enforcement revenue. This process required the employment of thousands of revenue officers, agents and special agents. Unfortunately, this type of enforcement happens every year and often spans to multiple previous years. In the end, there is still a large amount of tax money that goes unpaid. There's definitely a gap between the tax evader and the IRS. Evaders are usually exposed due to a slip-up on their part or a tip from a bystander. If you'd like to help close that gap, you can. But why should you, and how is it done? **Why Help the IRS?** Nobody likes paying more than their fair share of taxes in order to compensate for others who intentionally evade theirs. Why shouldn't tax evaders give up a portion of their incomes to provide things that benefit the general good, like roads and sewers, when you do? Reporting a tax cheat is like reporting a shoplifter - you're just asking them to pay for something they're trying to unfairly get for free. **Gather the Evidence** The IRS is not likely to pursue someone without good reason. If the time and resources are going to be spent, the odds need to be good that the efforts will result in a payoff. Besides determining who, what, where, when and why the person evaded his or her taxes, the IRS will need specific information (type of violation, availability of books or records). Having a hunch without supporting details just isn't good enough. Also ensure that the evasion is financially significant enough. For example, stating that your neighbor failed to report a $50 babysitting earning is not going to interest the IRS. On the other hand, if you work for a large business that you suspect is underreporting its income, the IRS will likely be very interested. **Blowing the Whistle on a Tax Cheat** The IRS may pay awards in exchange for valuable information that leads to the collection of \"\"taxes, penalties, interest or other amounts from the noncompliant taxpayer,\"\" according to the agency's website. There are various types of awards granted, depending on the evader's income level and classification (business or individual). The IRS likely chooses to focus its efforts on these larger cases because they have a higher payoff. It has also been suggested that higher income individuals have been found to cheat more frequently and for higher sums of money, mostly because they tend to earn more self-reported income. **Cover Your Assets** Fabricating a complaint in order to spite an undesirable neighbor who does, in fact, pay taxes is not a good way to get revenge. When you sign off on the IRS form providing your report, you are stating, \"\"I declare under penalty of perjury that I have examined this application, my accompanying statement and supporting documentation, and aver that such application is true, correct, and complete to the best of my knowledge.\"\" You don't want to be found guilty of perjury. **Keep It Legal** Breaking into the CFO's office at work to get evidence to support your claim is not a good idea. The IRS doesn't want you to break the law to help find a tax cheat. However, if you are the bookkeeper for a company that is cheating on its taxes and part of your job involves working with documents that prove the company is cheating, that paperwork would be acceptable to submit to the IRS. While the IRS wants to maintain your privacy, if the case against the person you report ends up going to trial, you could be asked to be a witness. If you're comfortable with that possibility, go ahead and put your name on the report. **Reasons Not to Report a Cheat** If your \"\"information\"\" is really just speculation, it's probably best to keep it to yourself. As explained earlier in this article, the IRS does not have the resources to pursue your hunch. If you, yourself, are a tax cheat, it might be best to stay in the clear. There's nothing that says that people who submit claims of cheating by others will have their own tax returns examined more carefully. Still, it stands to reason that you wouldn't want to do anything to call IRS attention to yourself if you're not in compliance with its rules. If you helped plan or initiate the cheating of the person you are reporting, it might be smart to think twice. If you decide to report a crime in which you took part, be prepared for the consequences, and definitely don't expect to receive a reward. As with many government processes, there's a lot of red tape to cut through. Therefore, if you're looking for fast cash, you might want to look elsewhere. It can take several years to complete an investigation of tax evasion – and if there is no conviction, there is no award. Not only does the IRS have to determine guilt, it has to actually collect the amount owed before paying you. What's more, if the IRS determines that your tip did not \"\"substantially contributed to the Service's detection and recovery of tax,\"\" you will not receive an award. It's also important to note that, under some circumstances, like attorney-client confidentiality, you may not be able to report tax cheating. **Other Considerations** If you earn a whistle blower award, it will need to be reported when you file your taxes. If you're blowing the whistle on your employer and you're not planning to change jobs, an IRS audit could make your work situation extremely unpleasant. This isn't to say that you shouldn't report someone who is cheating, but it is something to consider. **What's Next** If you decide to report the person or business you suspect of cheating, use IRS form3949-A. This form asks for basic information on the tax evader you are reporting, the types of violations you believe to be committed, the details of the violation and how you learned about it. If you do not want to fill out this form, you can also simply write the IRS a letter. If you are providing your name and want the possibility of receiving an award, also submit IRS Form 211 which is an application for the award. **The Bottom Line** Underpayment of federal income taxes (and, subsequently, state income taxes) is a serious problem. The IRS encourages people to submit tips by allowing anonymous submissions and offering generous rewards for informants who are willing to identify themselves. If you can substantiate your claims and are willing to accept the potential consequences of squealing, reporting a tax cheat can be lucrative not only for the government, but also for you. **Take Control of Your Money** Whether you’re buying a home, consolidating debt or Planning a Yearly Budget, Investopedia has the guide to overhauling your personal spending, saving and investing. [Click here](http://www.investopedia.com/accounts/signupnewsletter/?list=pf) to start managing your money like the pros.\"",
"title": ""
},
{
"docid": "445690",
"text": "US bank deposits over $10K only need to be reported to FinCEN (Financial Crimes Enforcement Network- a bureau of the US Department of Treasury) if the deposits are made in cash or other money instruments where the source cannot be traced (money orders, traveler checks, etc). Regular checks and wires don't need to be reported because there is a clear bank trail of where the money came from. If your family member is giving you money personally (not from a business) from a bank account which is outside of the US, then you only need to report it if the amount is over $100K. Note, you would need to report that regardless of whether the money was deposited into your US bank account, or paid directly to your credit cards on your behalf, and there are stiff penalties if you play games to try to avoid reporting requirements. Neither deposit method would trigger any taxable income for the scenario you described.",
"title": ""
},
{
"docid": "427589",
"text": "http://www.bills.com/private-student-loan-settlement/ Here is a page that seems to have specific advice on the matter. This site speculates that even though the private loan industry does not have to settle (and the private student loans, like federal loans cannot be discharged with a bankruptcy) they sometimes will anyway. http://www.huffingtonpost.com/2012/08/14/private-student-loans-bankruptcy-law_n_1753462.html ... If she could file bankruptcy to erase the private student loan debt she owes to Sallie Mae, she would. But because of a 2005 reform law, private student loans cannot be discharged in bankruptcy, except in extremely rare cases. ... The advice that works for you is the same advice with negotiating any debt. Get it in writing that the amount will constitute payment in full. Be sure that the written agreement makes some mention of how they will report it on your credit. (You are going to take a credit hit if you settle, but time will heal that.) The best plan is to pay, but if you can't, and you can honestly prove you can't, the debt collection company would be foolish to not take a settlement. They can wait around forever and sue you, add penalties and fees, but if you cannot pay, you cannot pay. I am going to guess because you are dealing with a debt collector, they are less vested in collecting the full amount. So get that settlement offer in writing. And don't be too much of a hard core negotiator. The power is all on their side. You will likely have to appeal to the greed of the collection company to succeed. Hope they would rather have $.50 today than $1.25 tomorrow.",
"title": ""
},
{
"docid": "179756",
"text": "I did find this information from the US Department of the Treasury: What are the penalties for withdrawing money early from a Time Certificate of Deposit (CD)? Federal law stipulates that all time certificates of deposit (CD) that are cashed out early are subject to a minimum penalty. If you withdraw an amount within the first six days after deposit, the penalty consists of at least seven days' simple interest. Other than that, national banks can set their own penalties; there is no maximum. Additionally, you may want to review the Account Agreement that the bank provided when you opened the account, as it explains the early withdrawal penalties. Check the paperwork to see if there is a short period at the start where the penalty is minimal. Each bank can set their own rules for the maximum penalty. Some base it on x months interest, some as a percentage of the CD, others may use a more complex formula.",
"title": ""
},
{
"docid": "584132",
"text": "\"Here are some reasons why it is advantageous to hold a portion of your savings in other countries: However, it should be noted that there are some drawbacks to holding funds in foreign banks: Don't worry; I haven't forgotten about the elephant in the room. What about tax evasion and money laundering? In general, simply transferring funds to a foreign jurisdiction will do nothing to help you evade taxes or hide evidence of a crime. Pretty much any method you can think of to transfer money is easily traceable, and any method that is difficult to trace is either illegal or heavily-regulated, with stiff penalties if you get caught. There are a few jurisdictions that have very strict banking privacy laws (the Philippines, for example). If you can somehow get the money into a bank account in one of these countries, you might be OK... at least, until that country's government decides (or is pressured) to change its banking privacy laws. But, what would you actually do with that money? Unless you want to go live in that country, you're going to have to transfer the funds out to spend them, and now you're right back on the radar — except now it's even worse, because the fact that the funds come from a suspicious jurisdiction will automatically cause your transfer to get flagged for investigation! This is where money laundering comes into play. There are lots of ways to go about this (exceptionally illegal) activity, many of which do not involve banks at all (at least, not directly). How money laundering works is outside the scope of this question, but in case you are curious, here are a couple of articles about the \"\"dark side\"\" of finance: In short, if you want to break the law, opening a foreign bank account isn't going to help much. In fact, the real crime is that offshore banking has such a criminal reputation in the first place! That said, it is possible to create legal distance between yourself and your money by using a corporate structure, and there are legitimate reasons why you might want to do this. Depending on which jurisdiction(s) you are a tax resident of, you can use this method to: Exactly how to do this is outside the scope of this question, but it's worth thinking about, especially if you have an interest in geopolitically diversifying your financial assets. If you're interested in learning more, I came across a pretty comprehensive article about Offshore Basics that covers how and why to set up offshore legal structures. (and yes, that makes now 4 links from the same site in one post! I promise it's just a coincidence; see disclaimer below) I am a US citizen with bank accounts in several countries (but not Switzerland; there are far better options out there right now). I have no affiliation with the website linked in this answer; while I was doing research for this answer, I found some really good supporting content, and it all just happened to be from the same source.\"",
"title": ""
},
{
"docid": "567206",
"text": "\"Let me give you some advice from someone who has experience at both ends - had student loan issues myself and parents ran financial aid department at local university. Quick story of my student loan. I graduated in debt and could not pay at first due to having kids way too early. I deferred. Schools will have rules for deference. There are also federal guidelines - lets not get specific on this though since these change every year it seems. So basically there is an initial deferment period in which any student can request for the repayments to be deferred and it is granted. Then there is an extended deferment. Here someone has to OK it. This is really rather arbitrary and up to the school/lender. My school decided to not extend mine after I filled out a mound of paperwork and showed that even without paying I had basically $200 a month for the family to live off past housing/fixed expenses. Eventually they had to cave, because I had no money so they gave me an extended deferment. After the 5 years I started paying. Since my school had a very complex way to pay, I decided to give them 6 months at a time. You would think they would love that right? (On the check it was clearly stated what months I was paying for to show that I was not prepaying the loan off) Well I was in collections 4 months later. Their billing messed up, set me up for prepayment. They then played dumb and acted like I didn't but I had a picture of the check and their bank's stamp on the back... They couldn't get my loan out of collections - even though they messed up. This is probably some lower level employee trying to cover their mistake. So this office tells creditors to leave me alone but I also CANNOT pay my loan because the credit collection agency has slapped a 5k fee on the 7k loan. So my loan spent 5 years (kid you not) like this. It was interest free since the employee stopped the loan processing. Point being is that if you don't pay the lender will either put your loan into deferment automatically or go after you. MOST (not all) schools will opt for deferment, which I believe is 2 years at most places. Then after that you have the optional deferment. So if you keep not paying they might throw you into that bucket. However if you stop paying and you never communicate with them the chances of you getting the optional deferment are almost none - unless school doesn't know where you live. Basically if you don't respond to their mail/emails you get swept into their credit collection process. So just filling out the deferment stuff when you get it - even if they deny it - could buy you up to 10 years - kid you not. Now once you go into the collection process... anything is game. As long as you don't need a home/car loan you can play this game. What the collection agency does depends on size of loan and the rules. If you are at a \"\"major\"\" university the rules are usually more lax, but if you are at the smaller schools, especially the advertised trade/online schools boom - better watch out. Wages will be garnished very soon. Expect to go to court, might have to hire an attorney because some corrupt lenders start smacking on fees - think of the 5k mine smacked on me. So the moral of the story is you will pay it off. If you act nice, fill out paperwork, talk to school, and so on you can probably push this off quite a few years. But you are still paying and you will pay interest on everything. So factor in that to the equation. I had a 2.3% loan but they are much higher now. Defaulting isn't always a bad thing. If you don't have the money then you don't have it. And using credit cards to help is not the thing to do. But you need to try to work with the school so you don't incur penalties/fees and so that your job doesn't have creditors calling them. My story ended year 4 that my loan was in collection. A higher up was reviewing my case and called me. Told her the story and emailed her a picture of their cashed check. She was completely embarrassed when she was trying to work out a plan for me and I am like - how about I come down tomorrow with the 7k. But even though lender admitted fault this took 20+ calls to agencies to clear up my credit so I could buy a house. So your goal should be:\"",
"title": ""
},
{
"docid": "550339",
"text": "\"Yes you should worry and take care not to violate the law or provide any appearance of impropriety. Every bank in the USA is required under the Bank Secrecy Act to report cash transactions over $10,000 the same day to the IRS -- and here's the fun secret part -- without notification to the depositor. But splitting the deposits up into smaller amounts is also a crime, called \"\"structuring\"\". On occasion there is a news story where a retail business that naturally must deposit cash from customers will be (falsely?) accused of structuring, e.g.: Feds seize grocery store's entire bank account -- Institute for Justice defends grocer Under the legal doctrine of civil asset forfeiture, your money can be accused of a crime, seized, and tried separately from its owner. The actual cases indicate the money as defendant, i.e. \"\"US v $124,700\"\" In this somewhat bizarre system of \"\"justice\"\", the owner need not be charged with a crime, and is not in immediate peril of going to prison (about the only upside in this, but might be temporary because the authorities haven't charged the owner yet). When only the money is charged with a crime, there is no requirement for the government to supply a public defender for the owners who can not afford a lawyer.... can not afford a lawyer, because the government took all their money....\"",
"title": ""
},
{
"docid": "1897",
"text": "Wire transfers normally run through either the Fedwire system or the Clearing House Interbank Payments System (CHIPS). The process generally works like this: You approach a bank or other financial institution and ask to transfer money. You give the bank a certain code, either an international bank account number or one of several other standards, which informs the bank where to send the money. The bank sends a message through a system like Fedwire to the receiving bank, along with settlement instructions. This is where the process can get a bit tricky. For the wire transfer to work, the banks must have reciprocal accounts with each other, or the sending bank must send the money to a bank that does have such an account with the receiver. If the sending bank sends the money to a third-party bank, the transaction is settled between them, and the money is then sent to the receiving bank from the third-party bank. This last transaction may be a wire transfer, ACH transfer, etc. The Federal Reserve fits into this because many banks hold accounts for this purpose with the Federal Reserve. This allows them to use the Fed as the third-party bank referred to above. Interestingly enough, this is one of the significant ways in which the Fed makes a profit, because it, along with every other bank and routing agent in the process, collects a miniscule fee on this process. You'll often find sources that state that Fedwire is only for transferring large transactions; while this is technically correct, it's important to understand that financial institutions don't settle every wire transfer or payment immediately. Although the orders are put in immediately, the financial institutions settle their transactions in bulk at the end of the business day, and even then they normally only settle the difference. So, if Chase owes Bank of America $1M, and Bank of America owes Chase $750K, they don't send these as two transactions; Chase simply credits BAC $250K. You didn't specifically ask about ACH transfers, which as littleadv pointed out, are different from wire transfers, but since ACH transfers can often form a part of the whole process, I'll explain that process too. ACH is a payment processing system that works through the Federal Reserve system, among others. The Federal Reserve (through the Fedline and FedACH systems) is by far the largest payment processor. The physical cash itself isn't transferred; in simple terms, the money is transferred through the ACH system between the accounts each bank maintains at the Federal Reserve. Here is a simple example of how the process works (I'm summarizing the example from Wikipedia). Let's say that Bob has an account with Chase and wants to get his paycheck from his employer, Stack Exchange, directly deposited into this account. Assume that Stack Exchange uses Bank of America as their bank. Bob, the receiver, fills out a direct deposit authorization form and gives it to his employer, called the originator. Once the originator has the authorization, they create an entry with an Originating Depository Financial Institution, which acts as a middleman between a payment processor (like the Federal Reserve) and the originator. The ODFI ensures that the transaction complies with the relevant regulations. In this example, Bank of America is the ODFI. Bank of America (the ODFI) converts the transaction request into an ACH entry and submits it, through an ACH operator, to the Receiving Depository Financial Institution (RDFI), which in this case is Chase bank. Chase credits (deposits) the paycheck in Bob's account. The Federal Reserve fits into all of this in several ways. Through systems like Fedline and FedACH, the Fed acts as an ACH operator, and the banks themselves also maintain accounts at the Federal Reserve, so it's the institution that actually performs the settling of accounts between banks.",
"title": ""
},
{
"docid": "565450",
"text": "First off, you should contact your health plan administrator as soon as possible. Different plans may interact differently with Medicare; any advice we could provide here would be tentative at best. Some of the issues you may face: A person with both Medicare and a QHP would potentially have primary coverage from 2 sources: Medicare and the QHP. No federal law addresses this situation. Under state insurance law an individual generally cannot collect full benefits from each of 2 policies that together pay more than an insured event costs. State law usually specifies how insurance companies will coordinate health benefits when a person has primary coverage from more than one source. In that situation, insurance companies determine which coverage is primary and which is secondary. It’s important to understand that a QHP is not structured to pay secondary benefits, nor are the premiums calculated or adjusted for secondary payment. In addition, a person with Medicare would no longer receive any premium assistance or subsidies under the federal law. While previous federal law makes it illegal for insurance companies to knowingly sell coverage that duplicates Medicare’s coverage when someone is entitled to or enrolled in Medicare Part A or Part B, there has been no guidance on the issue of someone who already has individual health insurance and then also enrolls in Medicare. We and other consumer organizations have asked state and federal officials for clarification on this complicated situation. As such, it likely is up to the plan how they choose to pay - and I wouldn't expect them to pay much if they think they can avoid it. You may also want to talk to someone at your local Medicare branch office - they may know more about your state specifically; or someone in your state's department of health/human services, or whomever administers the Exchanges (if it's not federal) in your state. Secondly, as far as enrolling for Part B, you should be aware that if she opts not to enroll in Part B at this time, if your wife later chooses to enroll before she turns 65 she will be required to pay a penalty of 10% per 12 month period she was not enrolled. This will revert to 0 when she turns 65 and is then eligible under normal rules, but it will apply every year until then. If she's enrolling during the normal General Enrollment period (Jan-March) then if she fails to enroll then she'll be required to pay that penalty if she later enrolls; if this is a Special Enrollment Period and extends beyond March, she may have the choice of enrolling next year without penalty.",
"title": ""
},
{
"docid": "383238",
"text": "What are the consequences if I ignore the emails? If you ignore the emails they will try harder to collect the money from you until they give up. Unlike what some other people here say, defaulting on a loan is NOT a crime and is NOT the same as stealing. There is a large number of reasons that can make someone unable to pay off a loan. Lenders are aware of the risk associated with default; they will try to collect the debt but at the end of the day if you don't have money/assets there is not much they can do. As far as immigration goes, there is nothing on a DS-160 form that asks you about bankruptcies or unpaid obligations. I doubt the consular officer will know of this situation, but it is possible. It is not grounds for visa ineligibility however, so you will be fine if everything else is fine. The only scenario in which unpaid student loans can come up relevant in immigration to the US is if and when you apply for US Citizenship. One of the requirements for Citizenship is having good moral character. Having a large amount of unpaid debt constitutes evidence of a poor moral character. But it is very unlikely you'd be denied Citizenship on grounds of that alone. I got a social security number when I took up on campus jobs at the school and I do have a credit score. Can they get a hold of this and report to the credit bureaus even though I don't live in America? Yes, they probably already have. How would this affect me if I visit America often? Does this mean I would not ever be able to live in America? No. See above. You will have a hard time borrowing again. Will they know when I come to America and arrest me at the border or can they take away my passport? No. Unpaid debt is no grounds for inadmissibility, so even if the CBP agent knows of it he will not do anything. And again, unpaid debt is not a crime so you will not be arrested.",
"title": ""
},
{
"docid": "285064",
"text": "Fundamentally interest rates reflect the time preference people place on money and the things money can buy. If I have a high time preference then I prefer money in my hand versus money promised to me at some date in the future. Thus, I will only loan my money to someone if they offer me an incentive which would be an amount of money to be received in the future that is larger than the amount of money I’m giving the debtor in the present (i.e. the interest rate). Many factors go into my time preference determination. My demand for cash (i.e. my cash balance), the credit rating of the borrower, the length of the loan, and my expectation of the change in currency value are just a few of the factors that affect what interest rate I will loan money. The first loan I make will have a lower interest rate than the last loan, ceteris paribus. This is because my supply of cash diminishes with each loan which makes my remaining cash more valuable and a higher interest rate will be needed to entice me to make additional loans. This is the theory behind why interest rates will rise when QE3 or QEinfinity ever stops. QE is where the Federal Reserve cartel prints new money to purchase bonds from cartel banks. If QE slows or ends the supply of money will stop increasing which will make cash more valuable and higher interest rates will be needed to entice creditors to loan money. Note that increasing the stock of money does not necessarily result in lower interest rates. As stated earlier, the change in value of the currency also affects the interest rate lenders are willing to accept. If the Federal Reserve cartel deposited $1 million everyday into every US citizen’s bank account it wouldn’t take long before lenders demanded very high interest rates as compensation for the decrease in the value of the currency. Does the Federal Reserve cartel affect interest rates? Yes, in two ways. First, as mentioned before, it prints new money that is loaned to the government. It either purchases the bonds directly or purchases the bonds from cartel banks which give them cash to purchase more government bonds. This keeps demand high for government bonds which lowers the yield on government bonds (yields move inverse to the price of the bond). The Federal Reserve cartel also can provide an unlimited amount of funds at the Federal Funds rate to the cartel member banks. Banks can borrow at this rate and then proceed to make loans at a higher rate and pocket the difference. Remember, however, that the Federal Reserve cartel is not the only market participant. Other bond holders, such as foreign governments and pension funds, buy and sell US bonds. At some point they could demand higher rates. The Federal Reserve cartel, which currently holds close to 17% of US public debt, could attempt to keep rates low by printing new money to buy all existing US bonds to prevent the yield on bonds from going up. At that point, however, holding US dollars becomes very dangerous as it is apparent the Federal Reserve cartel is just a money printing machine for the US government. That’s when most people begin to dump dollars en masse.",
"title": ""
},
{
"docid": "65914",
"text": "It would seem that the best method of bank robbery involves an inside man or woman, someone in the bank who can provide information about where the largest amount of cash is and when to hit the bank. $20,000 does not seem to be worth the risk of jail time. I'd say anything south of $100,000 per bank robber probably wouldn't be worth it, and getting that amount of cash would require more than a simple walk-in, pull a gun, empty a register robbery. The trick would either be proving an iron-clad alibi for the inside person or the group of robbers collectively contributing to the cost of that person disappearing. At the very least, that individual should get the largest share of the score. Escape is undoubtedly the biggest issue. One would need immediate transportation from the scene of the crime which could leave the area, then be dumped (fully scrubbed for prints, DNA, etc.) then the group would all go their separate ways. Regardless, I don't think it's worth the risk or the effort. First off, when you rob a bank the greedy bankers doesn't lose the money, it's paid by the FDIC, which is founded by taxpayers, so what you're doing is taking money that might otherwise be spent on social services for people who need them. Moreover, it's expensive and time-consuming to launder large amounts of money. If you manage to get $120,000 out of a robbery, which is hugely optimistic, that number would take years and a significant fraction of the take just to clean for personal use. And the risk of not only prison but possibly death seems rather extreme when compared to the admittedly more dull alternative of finding and holding down career. I think there are probably more efficient criminal methods of obtaining large quantities of money/wealth, too. Illegal narcotics, for example, are a $300 billion a year industry. While it's not the easiest business to get into, one imagines, the potential for someone who isn't just some moron off the street to climb the cartel ladder could be significant and could lead to a high income. There are significant risks, of course, and there's a serious moral question as to whether selling illegal drugs is acceptable or not, but if you're morally flexible or have the opinion that illegal narcotics are not something that should be prohibited, it could work. And there's always money in the banana stand.",
"title": ""
},
{
"docid": "545735",
"text": "This is a super contentious topic but we have to have a floor wage because we don't have a free labor market. In order for the labor market to come up with a fair wage the market must be as close to de-regulated as possible. But we've already seen what happens in an unregulated (or low regulation) market - safety problems, child labor, abysmal wages. Just ready a history book to see how the US clamped down on sweat shops, child labor and the rise of the Unions. No one wants to work like that so we put regulations in place to fix those things. This is why we have safety laws and rules to prevent our employers from stealing wages due to filing a report late or other stupid excuse. So we make the work places safer, and put protections in to make sure people get paid. But now we created a wage floor. Businesses are literally designed to make profit and you make profit by trimming all your expenses as much as necessary. Skilled employees have an easier time negotiating wages and they can band together in unions. But low skilled and unskilled workers don't have this ability so they work for minimum wage. Now regardless of a company's ability to pay their workers $15/hr or not, if you create a wage floor than don't account for yearly COLA/inflation workers get left behind. Why does this matter? There is a strong relationship between crime and poverty. So we decide to create social programs to keep crime down. But as the wage floor is not increased, min wage workers require more government subsidy. Either companies pay their employees enough where full time workers don't qualify for government subsidy or the government/tax payer ends up picking up the tab on behalf of these companies. You can't actually quantify the relationship between min wage and labor because it's not just a labor issue. It impacts crime, health (who has the ability to pay a $30 co pay if you're chronically ill on min wage?), and government social welfare on local,state and federal levels. We can't just demand that unskilled labors get skills so they get more money because that will end up devaluing skilled positions. Right now people argue that skilled positions are devalued when min wage increases. And that's true only if your employer fails to provide a like increase.",
"title": ""
},
{
"docid": "457338",
"text": "Based on these dates in your question: Going back over my records, I was able to recall the following: Maryland realized recently that on the 2009 Federal 1040 Form you stated that on December 31 2009 you liven in Maryland. They are wondering where the state tax form is. DC, MD and VA due to reciprocity collect income tax based on where you live not where you work. So when you moved in August 2009 and again in August 2010 you needed to file new state versions of the W4. The fact you did or didn't submit to your employer a correct state W-4 is not directly related, because you would owe the tax regardless. The W-4 just makes sure that something close to the correct amounts are withheld and sent to the appropriate state capital. I seem to remember something about not having to pay Maryland state taxes since I not only lived in the state for less than 6 months but also did not work in the state. The reciprocity between DC, MD and VA says that Maryland gets the money because that is where you lived. The last time I had to do a part year the law was that they would forgive a half a month. In other words if you move in late December or early January you could ignore that small time period and avoid having to file in two states. In some cases people argue that some short term moves were never meant to be permanent. You might be able to claim that except the fact that your 2009 federal tax form you most likely claimed you lived in Maryland. The next issue is time and money. If Maryland says you owe them money for that time period, and if they still have the ability to force you to pay it; This is where the issue of correct state W-4 comes in. If the money during the period you lived in Maryland was sent to Virginia, you should have had that money refunded by Richmond in the spring of 2010. But if there was no W-4 filed with your employer that would mean that Maryland didn't get any money for 2009. If you didn't tell Richmond you moved in 2009 they may not have refunded everything because they thought you lived there all year. Because of the time that has passed it may be too late to fix your Virginia filing, so they may not refund you excess payment to them. Maryland is interested in calculating how much you should have paid them in 2009. They are only looking at what you told the feds you made, and they may be assuming that you lived there the whole year. But until you file correctly that have no ability to calculate what you really owe. You need professional advice. You need to know what they can and can't collect. You also need to know what you can and can't get back from Richmond. And since it also may impact your filings for 2010 you will want to get that resolved at the same time.",
"title": ""
},
{
"docid": "316051",
"text": "\"is your credit history ruined, or merely dinged? Is the blow recoverable? Any bad credit rating event is recoverable given enough time / money to solve the problem. As far as \"\"Ruined\"\" vs\"\" \"\"Dinged\"\", well, that's a matter of opinion; some people think that one bad item is the end of the world, others not so much. You will have an unpaid debt listed on your report. This will drop your score. The amount it impacts the score will depend on other factors in your report. Can the carrier try to get the money back in court? I assume you'll wind up dealing with a debt collector. Yes they could go to court, but that's unlikely at least in the short term. Far more likely is that the debt ends up sold to a debt collection agency for pennies on the dollar. The debt collection agency will harass you until you pay and they might file in court if they think the debt is more than enough to cover the court costs. Will this affect any other relationships you have? Possibly. A bad rating may make it more difficult to get credit in the future. However that depends on numerous other factors such as your entire history. It could even prevent you from being hired from certain jobs - not many of them, but some. Is it criminal? Read this: http://www.startribune.com/investigators/95692619.html The US does NOT have a debtors prison. However if the company decides to file a court case and you fail to appear or fail to abide by the court ruling then, in some states, you could be committing a crime and may be thrown in jail. At which point you are on the hook not just for the original fee but potentially a plethora of other costs. Never mind the loss of reputation when your friends, family and coworkers find out that you are sitting in jail. At the end of the day, just pay the debt. If you agreed to the plan and the plan has an early cancellation fee then the moral and ethical thing to do is pay it. Trying to see how bad it would be to ignore it isn't the right way to live.\"",
"title": ""
},
{
"docid": "283546",
"text": "\">*Higher taxes aren't generally a path to economic growth and job creation. Higher cigarette taxes, however, are increasingly boosting at least one sector of the economy, organized crime.* >*'Smuggled cigarettes have become the new currency of organized crime, and a lot of these criminal organizations are finding that it’s more profitable than illegal narcotics,' Rich Marianos, the retired Assistant Director of the Bureau of Alcohol, Tobacco and Firearms,recently noted.* >*Marianos said that black market tobacco smuggling has become \"\"a high-profit, low-risk criminal enterprise. Compared to drug offenses where there’s a mandatory minimum sentence, there’s no penalties out there for the cigarette trafficker.\"\"* >*'They’re being sold in the bodegas, in the convenience stores, they’re being sold on the street, they’re being sold in the housing projects,” Marianos said, “by street gangs like the Latin Kings, terrorist organizations, the Russian Mafia.'\"\"* >*Politicians love raising tobacco taxes. With the number of smokers continuing to fall, fewer voters feel the pain of the higher taxes directly. Last year, three states raised their cigarette taxes, even though the states were enjoying higher tax revenue.* >*The political addiction to higher cigarette taxes is creating a boon for organized crime. Last month, the Tax Foundation, in testimony before the US Senate, noted that over 56% of the cigarettes sold in New York State were smuggled in from other states. New York has the highest tax on cigarettes in the country.* Cross-post from /r/MAConservative\"",
"title": ""
},
{
"docid": "236732",
"text": "\"The 529 plan does outline your scenarios. There are stipulations for providing the funds should the child get the scholarship. If the child decides not to go into further education (vocational and community schools count), the money can be withdrawn with a 10% penalty and taxes paid on interest earnings. Taxes wouldn't have to be paid for contributions as taxes were already paid on that money by the gift giver. The 529 could also be transferred to another child in the family (including grandchildren). Here's an excerpt from www.savingforcollege.com: You'll never lose all of your savings. A 529 plan offers tax-free earnings and tax-free withdrawals as long as the money is used to pay for college. If you end up taking a non-qualified withdrawal, you'll incur income tax as well as a 10% penalty - but only on the earnings portion of the withdrawal. Since your contributions were made with after-tax money, they will never be taxed or penalized. You can avoid the penalty if you get a scholarship. There are a few special exceptions to the 10% penalty rule, including when the beneficiary becomes incapacitated, attends a U.S. Military Academy or gets a scholarship. In the case of a scholarship, non-qualified withdrawals up to the amount of the tax-free scholarship can be taken out penalty-free, but you'll have to pay income tax on the earnings. As Savingforcollege.com founder Joe Hurley likes to say, \"\"the scholarships have turned your tax-free 529 investment into a tax-deferred 529 investment\"\". Note, a 529 is ideal for the sum of money you are looking at. A proper trust, set up by a lawyer, will cost as much as $2000 to set up, and would require an annual tax return, both unnecessary burdens. To make matters worse, the trust counts as the child's asset where financial aid is concerned. The 529 counts, but to a much lesser extent.\"",
"title": ""
},
{
"docid": "239780",
"text": "\">SS is not an investment. It is a Tax. Learn the difference. Thus you pay for it with the Federal Insurance Contributions Act tax (FICA). It is not an investment, you do not have an account with your money, it has always been a pay as you go plan, just like medicare, funds for schools, and all the other programs. SS is collected like a tax, but if it is infact a tax, why can I opt out of it? Come on, you really aren't trying to win an arguement about SS by saying its a \"\"tax\"\" and not a \"\"investment\"\". That's seriously the weakest bullshit, who the fuck cares the symantics of how its \"\"collected\"\".. The arguement is still the same, with no USA no SS. It is, therefore, a ponzi by definition. >The US government wrote the laws that specify exactly who can opt out. Most people cannot just opt out because they don't meet the criteria. Again you're wrong. Joining and quitting Obtaining a Social Security number for a child is voluntary.[26] Further, there is no general legal requirement that individuals join the Social Security program (although, under normal circumstances, FICA taxes must be collected anyway). Although the Social Security Act itself does not require a person to have a Social Security Number (SSN) to live and work in the United States,[27] the Internal Revenue Code does generally require the use of the social security number by individuals for federal tax purposes: The social security account number issued to an individual for purposes of section 205(c)(2)(A) of the Social Security Act shall, except as shall otherwise be specified under regulations of the Secretary [of the Treasury or his delegate], be used as the identifying number for such individual for purposes of this title.[28] Importantly, most parents apply for Social Security numbers for their dependent children in order to[29] include them on their income tax returns as a dependent. Everyone filing a tax return, as taxpayer or spouse, must have a Social Security Number or Taxpayer Identification Number (TIN) since the IRS is unable to process returns or post payments for anyone without an SSN or TIN. The FICA taxes are imposed on all workers and self-employed persons. Employers are required[30] to report wages for covered employment to Social Security for processing Forms W-2 and W-3. There are some specific wages which are not a part of the Social Security program (discussed below). Internal Revenue Code provisions section 3101[31] imposes payroll taxes on individuals and employer matching taxes. Section 3102[32] mandates that employers deduct these payroll taxes from workers' wages before they are paid. Generally, the payroll tax is imposed on everyone in employment earning \"\"wages\"\" as defined in 3121[33] of the Internal Revenue Code.[34] and also taxes[35] net earnings from self-employment.[36] **Seriously, you need to learn how to use google asshole. Stop looking like an idiot and posting blatent lies.**\"",
"title": ""
},
{
"docid": "80769",
"text": "I can't address Indian law but US law has no problems with you having savings accounts in India. Furthermore, there are no tax consequences from paying off the student loan. However there is big problem here--while the US has no rules against foreign bank accounts it has reporting rules that you certainly have violated (if you hadn't violated them you wouldn't be asking the question.) 1) Those foreign bank accounts must be listed on your tax return. 2) Those foreign bank accounts must be listed on a PDF that's filed with the (Financial Crimes Enforcement Network. (Yes, it's very stupid they need identical information sent to two different departments.) 2) The interest you earned on that bank account is income that should have been reported on your return. As for what to do about it--this is the realm where you get professional help. As for the outcome--since you didn't set out to cheat they have a much less harsh system set up. Expect to amend your 2012 and 2013 returns (and 2014 if you've already filed it), pay interest and late-payment penalties on the additional tax caused by the interest and pay a penalty of 5% of the highest total value of the accounts. Since the discovery of large amounts of money being hidden from the taxman in Swiss bank accounts Congress has gone 1000# gorilla about it and been pressuring foreign banks to cough up the details on any US-citizen or US-resident depositors.",
"title": ""
},
{
"docid": "304179",
"text": "You signed a contract to pay the loan. You owe the money. Stories of people being arrested over defaulted student loans are usually based in contempt of court warrants when the person failed to appear in court when the collection agency filed suit against them. Explore student loan forgiveness program. Research collections and bankruptcy and how to deal with collection agencies. There are pitfalls in communicating with them which restart the clock on bad debt aging off the credit report, and which can be used to say that you agreed to pay a debt. For instance, if you make any sort of payment on any debt, a case can be made that you have assumed the debt. Once you are aware of the pitfalls, contact the collection agency (in writing) and dispute the debt. Force them to prove that it is your debt. Force them to prove that they have the right to collect it. Force them to prove the amount. Dispute the fairness of the amount. Doubling your principal in 6 years is a bit flagrant. So, work with the collectors, establish that the debt is valid and negotiate a settlement. Or let it stay in default. Your credit report in the US is shot. It will be a long time before the default ages off your report. This is important if you try to open a bank account, rent an apartment, or get a job in the US. These activities do not always require a credit report, but they often do. You will not be able to borrow money or establish a credit card in the US. Here's a decent informational site regarding what they can do to collect the loan. Pay special attention to Administrative Wage Garnishment. They can likely hit you with that one. You might be unreachable for a court summons, but AWG only requires that the collectors be able to confirm that you work for a company that is subject to US laws. Update: I am informed that federally funded student loans are not available to international students. AWG is only possible for debts to the federal government. Private companies must go through the courts to force settlement of debt. OP is safe from AWG.",
"title": ""
},
{
"docid": "594320",
"text": "\"> and very doubtful once normalized for socioeconomics that race is at all a factor. Very doubtful? Once you account for socioeconomic status in violent crime, you find that blacks commit way more violent crime. For example, there are twice as many white people under the poverty line in America than there are poor black people. And yet, [you get these results](https://infogram.com/us-crime-in-black-and-white-1gzxop49q0okmwy). So that's one instance where \"\"controlling for socioeconomic\"\" status doesn't matter. Culture has more of an impact than you think. My friend works in an insurance industry where the target market is poor people. He no longer advertises heavily in black communities, after tracking his stats for years, as inevitably over 50% of his black clients do not pay their bills unless you literally swing by their house to collect the check whenever they forget to pay. Meanwhile, white people with the same amount of wealth stay on the books over 90% of the time after signing up. How do you explain that? This study indicates that not everybody should be getting degrees. And certainly not joke degrees that leave people unemployable/in debt.\"",
"title": ""
},
{
"docid": "539929",
"text": "\"Why does it have to be a central authority? We collect taxes on local, state, and federal levels. My question is that we, in the USA are (in my opinion) to fixated on the taxes that rich people might pay and that if we \"\"anger them\"\" with higher taxes, they will run away. Where is the concern for the welfare of the working man and his family?\"",
"title": ""
},
{
"docid": "12391",
"text": "\"Accept that the money's gone. It could, as others have mentioned, been a lot more. Learn. Make sure your son (and you!) have learned the lesson (at least try to get something out of the $650). The world isn't always a nice place unfortunately. Don't wire money to strangers - use an escrow service or paypal or similar. As the saying goes: \"\"Fool me once, shame on you. Fool me twice, shame on me\"\". Report it to the authorities. Does have the advantage of the domestic rather than foreign bank account used. The scammer might have closed it by now, but there should be some paper tail. I imagine the id required for opening a bank account in the US is as strict as it is most places these days. They may have used fake Id, but that's not your problem. Assuming contact was made over the internet, bearing in mind IANAL (or American), this could be a crime of Wire Fraud, in which case I believe it's a case for the FBI rather than your local police. The phone calls your son is still receiving could also be construed as attempted extortion and if across state lines could also come under federal jurisdiction. The FBI have a better chance of catching such a scammer, generally having more chance of knowing one end of a computer from the other compared to a local beat cop. If other victims have also contacted the authorities, it will probably be taken more seriously. Give as much information as you can. Not just the bank account details, but all communication, exact time of phone calls, etc. The cops may say there's nothing they can do as it's a civil matter (breach of contract) rather than a criminal one. In which case you have the (probably expensive) option of going the civil route as described by Harper above. Inform Others. Assuming initial contact with the scammer was made through a website or forum or similar. I imagine this must be a niche area for hand made toys. Post your experience to warn other potential victims. Inform the site owner - they may ban the scammers account where applicable. Stop the calls. Block the number. If the number's being withheld, contact the provider - they should have a policy regarding harassment and be able to block it their end. If the calls keep coming, your son will need to change his number. Don’t let it get to you. You may have warm cosy fantasies of removing the guys kneecaps with a 2x4. Don't however dwell on the b*stard for too long and let it get under your skin. You will have to let it go.\"",
"title": ""
},
{
"docid": "127974",
"text": "There is a shortcut you can use when calculating federal estimated taxes. Some states may allow the same type of estimation, but I know at least one (my own--Illinois) that does not. The shortcut: you can completely base your estimated taxes for this year on last year's tax return and avoid any underpayment penalty. A quick summary can be found here (emphasis mine): If your prior year Adjusted Gross Income was $150,000 or less, then you can avoid a penalty if you pay either 90 percent of this year's income tax liability or 100 percent of your income tax liability from last year (dividing what you paid last year into four quarterly payments). This rule helps if you have a big spike in income one year, say, because you sell an investment for a huge gain or win the lottery. If wage withholding for the year equals the amount of tax you owed in the previous year, then you wouldn't need to pay estimated taxes, no matter how much extra tax you owe on your windfall. Note that this does not mean you will not owe money when you file your return next April; this shortcut ensures that you pay at least the minimum allowed to avoid penalty. You can see this for yourself by filling out the worksheet on form 1040ES. Line 14a is what your expected tax this year will be, based on your estimated income. Line 14b is your total tax from last year, possibly with some other modifications. Line 14c then asks you to take the lesser of the two numbers. So even if your expected tax this year is one million dollars, you can still base your estimated payments on last year's tax.",
"title": ""
},
{
"docid": "332626",
"text": "\"The IRS taxes worldwide income of its citizens and green card holders. Generally, for those Americans genuinely living/working overseas the IRS takes the somewhat reasonable position of being in \"\"2nd place\"\" tax-wise. That is, you are expected to pay taxes in the country you are living in, and these taxes can reduce the tax you would have owed in the USA. Unfortunately, all of this has to be documented and tax returns are still required every year. Your European friends may find this quite surprising as I've heard, for instance, that France will not tax you if you go live and work in Germany. A foreign company operating in a foreign country under foreign law is not typically required to give you a W-2, 1099, or any of the forms you are used to. Indeed, you should be paying taxes in the place where you live and work, which is probably somewhat different than the USA. Keep all these records as they may be useful for your USA taxes as well. You are required to total up what you were paid in Euros and convert them to US$. This will go on the income section of a 1040. You should be paying taxes in the EU country where you live. You can also total those up and convert to US$. This may be useful for a foreign tax credit. If you are living in the EU long term, like over 330 days/year or you have your home and family there, then you might qualify for a very large exemption from your income for US tax purposes, called the Foreign Earned Income Exclusion. This is explained in IRS Publication 54. The purpose of this is primarily to avoid double taxation. FBAR is a serious thing. In past years, the FBAR form went to a Financial Crimes unit in Detroit, not the regular IRS address. Also, getting an extension to file taxes does not extend the deadline for the FBAR. Some rich people have paid multi-million dollar fines over FBAR and not paying taxes on foreign accounts. I've heard you can get a $10,000 FBAR penalty for inadvertent, non-willful violations so be sure to send those in and it goes up from there to $250k or half the value of the account, whichever is more. You also need to know about whether you need to do FATCA reporting with your 1040. There are indeed, a lot of obnoxious things you need to know about that came into existence over the years and are still on the law books -- because of the perpetual 'arms race' between the government and would be cheaters, non-payers and their advisors. http://www.irs.gov/publications/p54/ http://americansabroad.org/\"",
"title": ""
},
{
"docid": "247390",
"text": "And where is the money going from these collections? I hope this doesn't become some money collecting scheme that doesn't do much to help the environment. If it's being collected by any government organization, most likely the money will first pay the salary of some goddamn bureuocrat. Would be best if the money went to some scientific organization or to scientists or researchers...wishful thinking probably",
"title": ""
}
] |
372
|
Eilat virus (EILV) produced in mosquitos elicits rapid and long-lasting neutralizing antibodies in nonhuman primates.
|
[
{
"docid": "24922825",
"text": "Traditionally, vaccine development involves tradeoffs between immunogenicity and safety. Live-attenuated vaccines typically offer rapid and durable immunity but have reduced safety when compared to inactivated vaccines. In contrast, the inability of inactivated vaccines to replicate enhances safety at the expense of immunogenicity, often necessitating multiple doses and boosters. To overcome these tradeoffs, we developed the insect-specific alphavirus, Eilat virus (EILV), as a vaccine platform. To address the chikungunya fever (CHIKF) pandemic, we used an EILV cDNA clone to design a chimeric virus containing the chikungunya virus (CHIKV) structural proteins. The recombinant EILV/CHIKV was structurally identical at 10 Å to wild-type CHIKV, as determined by single-particle cryo-electron microscopy, and it mimicked the early stages of CHIKV replication in vertebrate cells from attachment and entry to viral RNA delivery. Yet the recombinant virus remained completely defective for productive replication, providing a high degree of safety. A single dose of EILV/CHIKV produced in mosquito cells elicited rapid (within 4 d) and long-lasting (>290 d) neutralizing antibodies that provided complete protection in two different mouse models. In nonhuman primates, EILV/CHIKV elicited rapid and robust immunity that protected against viremia and telemetrically monitored fever. Our EILV platform represents the first structurally native application of an insect-specific virus in preclinical vaccine development and highlights the potential application of such viruses in vaccinology.",
"title": "A chikungunya fever vaccine utilizing an insect-specific virus platform"
}
] |
[
{
"docid": "8883846",
"text": "The Global HIV Vaccine Enterprise convened a two-day workshop in May of 2007 to discuss humoral immune responses to HIV and approaches to design vaccines that induce viral neutralizing and other potentially protective antibody responses. The goals of this workshop were to identify key scientific issues, gaps, and opportunities that have emerged since the Enterprise Strategic Plan was first published in 2005 [1], and to make recommendations that Enterprise stakeholders can use to plan new activities. Most effective viral vaccines work, at least in part, by generating antibodies that inactivate or neutralize the invading virus, and the existing data strongly suggest that an optimally effective HIV-1 vaccine should elicit potent antiviral neutralizing antibodies. However, unlike acute viral pathogens, HIV-1 chronically replicates in the host and evades the antibody response. This immune evasion, along with the large genetic variation among HIV-1 strains worldwide, has posed major obstacles to vaccine development. Current HIV vaccine candidates do not elicit neutralizing antibodies against most circulating virus strains, and thus the induction of a protective antibody response remains a major priority for HIV-1 vaccine development. For an antibody-based HIV-1 vaccine, progress in vaccine design is generally gauged by in vitro assays that measure the ability of vaccine-induced antibodies to neutralize a broad spectrum of viral isolates representing the major genetic subtypes (clades) of HIV-1 [2]. Although it is not known what magnitude and breadth of neutralization will predict protection in vaccine recipients, it is clear that current vaccine immunogens elicit antibodies that neutralize only a minority of circulating isolates. Thus, much progress needs to be made in this area. Also, though virus neutralization is considered a critical benchmark for a vaccine, this may not be the only benchmark for predicting success with antibody-based HIV-1 vaccine immunogens. The main targets for neutralizing antibodies to HIV-1 are the surface gp120 and trans-membrane gp41 envelope glycoproteins (Env) that mediate receptor and coreceptor binding and the subsequent membrane fusion events that allow the virus to gain entry into cells [3]. Antibodies neutralize the virus by binding these viral spikes and blocking virus entry into susceptible cells, such as CD4+ T cells [4,5]. In order to chronically replicate in the host, the virus exploits several mechanisms to shield itself against antibody recognition, including a dense outer coating of sugar molecules (N-linked glycans) and the strategic positioning of cysteine–cysteine loop structures on the gp120 molecule [6–8]. These shielding mechanisms, although highly effective, have vulnerabilities imposed by fitness constraints. Information on the precise location and molecular structure of these vulnerable regions could be valuable for the rational design of improved vaccine immunogens. Participants in the workshop identified four areas that, if given proper attention, could provide key information that would bring the field closer to an effective antibody-based HIV-1 vaccine: (1) structure-assisted immunogen design, (2) role of Fc receptors and complement, (3) assay standardization and validation, and (4) immunoregulation of B cell responses.",
"title": "Antibody-Based HIV-1 Vaccines: Recent Developments and Future Directions"
},
{
"docid": "3566945",
"text": "Broadly neutralizing antibodies (bnAbs) to HIV-1 can evolve after years of an iterative process of virus escape and antibody adaptation that HIV-1 vaccine design seeks to mimic. To enable this, properties that render HIV-1 envelopes (Env) capable of eliciting bnAb responses need to be defined. Here, we followed the evolution of the V2 apex directed bnAb lineage VRC26 in the HIV-1 subtype C superinfected donor CAP256 to investigate the phenotypic changes of the virus populations circulating before and during the early phases of bnAb induction. Longitudinal viruses that evolved from the VRC26-resistant primary infecting (PI) virus, the VRC26-sensitive superinfecting (SU) virus and ensuing PI-SU recombinants revealed substantial phenotypic changes in Env, with a switch in Env properties coinciding with early resistance to VRC26. Decreased sensitivity of SU-like viruses to VRC26 was linked with reduced infectivity, altered entry kinetics and lower sensitivity to neutralization after CD4 attachment. VRC26 maintained neutralization activity against cell-associated CAP256 virus, indicating that escape through the cell-cell transmission route is not a dominant escape pathway. Reduced fitness of the early escape variants and sustained sensitivity in cell-cell transmission are both features that limit virus replication, thereby impeding rapid escape. This supports a scenario where VRC26 allowed only partial viral escape for a prolonged period, possibly increasing the time window for bnAb maturation. Collectively, our data highlight the phenotypic plasticity of the HIV-1 Env in evading bnAb pressure and the need to consider phenotypic traits when selecting and designing Env immunogens. Combinations of Env variants with differential phenotypic patterns and bnAb sensitivity, as we describe here for CAP256, may maximize the potential for inducing bnAb responses by vaccination.",
"title": "Phenotypic deficits in the HIV-1 envelope are associated with the maturation of a V2-directed broadly neutralizing antibody lineage"
},
{
"docid": "7177329",
"text": "Neutralizing antibodies are likely to play a crucial part in a preventative HIV-1 vaccine. Although efforts to elicit broadly cross-neutralizing (BCN) antibodies by vaccination have been unsuccessful, a minority of individuals naturally develop these antibodies after many years of infection. How such antibodies arise, and the role of viral evolution in shaping these responses, is unknown. Here we show, in two HIV-1–infected individuals who developed BCN antibodies targeting the glycan at Asn332 on the gp120 envelope, that this glycan was absent on the initial infecting virus. However, this BCN epitope evolved within 6 months, through immune escape from earlier strain-specific antibodies that resulted in a shift of a glycan to position 332. Both viruses that lacked the glycan at amino acid 332 were resistant to the Asn332-dependent BCN monoclonal antibody PGT128 (ref. 8), whereas escaped variants that acquired this glycan were sensitive. Analysis of large sequence and neutralization data sets showed the 332 glycan to be significantly under-represented in transmitted subtype C viruses compared to chronic viruses, with the absence of this glycan corresponding with resistance to PGT128. These findings highlight the dynamic interplay between early antibodies and viral escape in driving the evolution of conserved BCN antibody epitopes.",
"title": "Evolution of an HIV glycan–dependent broadly neutralizing antibody epitope through immune escape"
},
{
"docid": "1071991",
"text": "Live attenuated simian immunodeficiency virus (SIV) vaccines (LAVs) remain the most efficacious of all vaccines in nonhuman primate models of HIV and AIDS, yet the basis of their robust protection remains poorly understood. Here we show that the degree of LAV-mediated protection against intravenous wild-type SIVmac239 challenge strongly correlates with the magnitude and function of SIV-specific, effector-differentiated T cells in the lymph node but not with the responses of such T cells in the blood or with other cellular, humoral and innate immune parameters. We found that maintenance of protective T cell responses is associated with persistent LAV replication in the lymph node, which occurs almost exclusively in follicular helper T cells. Thus, effective LAVs maintain lymphoid tissue-based, effector-differentiated, SIV-specific T cells that intercept and suppress early wild-type SIV amplification and, if present in sufficient frequencies, can completely control and perhaps clear infection, an observation that provides a rationale for the development of safe, persistent vectors that can elicit and maintain such responses.",
"title": "Lymph node T cell responses predict the efficacy of live attenuated SIV vaccines"
},
{
"docid": "14195528",
"text": "The role of primate frontal cortex in vocal communication and its significance in language evolution have a controversial history. While evidence indicates that vocalization processing occurs in ventrolateral prefrontal cortex neurons, vocal-motor activity has been conjectured to be primarily subcortical and suggestive of a distinctly different neural architecture from humans. Direct evidence of neural activity during natural vocal communication is limited, as previous studies were performed in chair-restrained animals. Here we recorded the activity of single neurons across multiple regions of prefrontal and premotor cortex while freely moving marmosets engaged in a natural vocal behavior known as antiphonal calling. Our aim was to test whether neurons in marmoset frontal cortex exhibited responses during vocal-signal processing and/or vocal-motor production in the context of active, natural communication. We observed motor-related changes in single neuron activity during vocal production, but relatively weak sensory responses for vocalization processing during this natural behavior. Vocal-motor responses occurred both prior to and during call production and were typically coupled to the timing of each vocalization pulse. Despite the relatively weak sensory responses a population classifier was able to distinguish between neural activity that occurred during presentations of vocalization stimuli that elicited an antiphonal response and those that did not. These findings are suggestive of the role that nonhuman primate frontal cortex neurons play in natural communication and provide an important foundation for more explicit tests of the functional contributions of these neocortical areas during vocal behaviors.",
"title": "Responses of primate frontal cortex neurons during natural vocal communication."
},
{
"docid": "2601135",
"text": "A recent study of plasma neutralization breadth in HIV-1 infected individuals at nine International AIDS Vaccine Initiative (IAVI) sites reported that viral load, HLA-A*03 genotype, and subtype C infection were strongly associated with the development of neutralization breadth. Here, we refine the findings of that study by analyzing the impact of the transmitted/founder (T/F) envelope (Env), early Env diversification, and autologous neutralization on the development of plasma neutralization breadth in 21 participants identified during recent infection at two of those sites: Kigali, Rwanda (n = 9) and Lusaka, Zambia (n = 12). Single-genome analysis of full-length T/F Env sequences revealed that all 21 individuals were infected with a highly homogeneous population of viral variants, which were categorized as subtype C (n = 12), A1 (n = 7), or recombinant AC (n = 2). An extensive amino acid sequence-based analysis of variable loop lengths and glycosylation patterns in the T/F Envs revealed that a lower ratio of NXS to NXT-encoded glycan motifs correlated with neutralization breadth. Further analysis comparing amino acid sequence changes, insertions/deletions, and glycan motif alterations between the T/F Env and autologous early Env variants revealed that extensive diversification focused in the V2, V4, and V5 regions of gp120, accompanied by contemporaneous viral escape, significantly favored the development of breadth. These results suggest that more efficient glycosylation of subtype A and C T/F Envs through fewer NXS-encoded glycan sites is more likely to elicit antibodies that can transition from autologous to heterologous neutralizing activity following exposure to gp120 diversification. This initiates an Env-antibody co-evolution cycle that increases neutralization breadth, and is further augmented over time by additional viral and host factors. These findings suggest that understanding how variation in the efficiency of site-specific glycosylation influences neutralizing antibody elicitation and targeting could advance the design of immunogens aimed at inducing antibodies that can transition from autologous to heterologous neutralizing activity.",
"title": "Diversification in the HIV-1 Envelope Hyper-variable Domains V2, V4, and V5 and Higher Probability of Transmitted/Founder Envelope Glycosylation Favor the Development of Heterologous Neutralization Breadth"
},
{
"docid": "8063697",
"text": "Pertussis is a highly contagious respiratory illness caused by the bacterial pathogen Bordetella pertussis. Pertussis rates in the United States have been rising and reached a 50-y high of 42,000 cases in 2012. Although pertussis resurgence is not completely understood, we hypothesize that current acellular pertussis (aP) vaccines fail to prevent colonization and transmission. To test our hypothesis, infant baboons were vaccinated at 2, 4, and 6 mo of age with aP or whole-cell pertussis (wP) vaccines and challenged with B. pertussis at 7 mo. Infection was followed by quantifying colonization in nasopharyngeal washes and monitoring leukocytosis and symptoms. Baboons vaccinated with aP were protected from severe pertussis-associated symptoms but not from colonization, did not clear the infection faster than naïve animals, and readily transmitted B. pertussis to unvaccinated contacts. Vaccination with wP induced a more rapid clearance compared with naïve and aP-vaccinated animals. By comparison, previously infected animals were not colonized upon secondary infection. Although all vaccinated and previously infected animals had robust serum antibody responses, we found key differences in T-cell immunity. Previously infected animals and wP-vaccinated animals possess strong B. pertussis-specific T helper 17 (Th17) memory and Th1 memory, whereas aP vaccination induced a Th1/Th2 response instead. The observation that aP, which induces an immune response mismatched to that induced by natural infection, fails to prevent colonization or transmission provides a plausible explanation for the resurgence of pertussis and suggests that optimal control of pertussis will require the development of improved vaccines.",
"title": "Acellular pertussis vaccines protect against disease but fail to prevent infection and transmission in a nonhuman primate model."
},
{
"docid": "23915841",
"text": "The study of the evolution and specificities of neutralizing antibodies during the course of human immunodeficiency virus type 1 (HIV-1) infection may be important in the discovery of possible targets for vaccine design. In this study, we assessed the autologous and heterologous neutralization responses of 14 HIV-1 subtype C-infected individuals, using envelope clones obtained within the first 2 months postinfection. Our data show that potent but relatively strain-specific neutralizing antibodies develop within 3 to 12 months of HIV-1 infection. The magnitude of this response was associated with shorter V1-to-V5 envelope lengths and fewer glycosylation sites, particularly in the V1-V2 region. Anti-MPER antibodies were detected in 4 of 14 individuals within a year of infection, while antibodies to CD4-induced (CD4i) epitopes developed to high titers in 12 participants, in most cases before the development of autologous neutralizing antibodies. However, neither anti-MPER nor anti-CD4i antibody specificity conferred neutralization breadth. These data provide insights into the kinetics, potency, breadth, and epitope specificity of neutralizing antibody responses in acute HIV-1 subtype C infection.",
"title": "Neutralizing antibody responses in acute human immunodeficiency virus type 1 subtype C infection."
},
{
"docid": "38376189",
"text": "West Nile virus (WNV) is a major cause of mosquito-borne illness in the United States. Human disease ranges from mild febrile illness to severe fatal neurologic infection. Adults aged >60 years are more susceptible to neuroinvasive disease accompanied by a high mortality rate or long-lasting neurologic sequelae. A chimeric live attenuated West Nile virus vaccine, rWN/DEN4&Dgr;30, was shown to be safe and immunogenic in healthy adults aged 18–50 years. This study evaluated rWN/DEN4&Dgr;30 in flavivirus-naive adults aged 50–65 years and found it to be safe and immunogenic. Outbreaks of WNV infection tend to be unpredictable, and a safe and effective vaccine will be an important public health tool.",
"title": "A Live Attenuated Chimeric West Nile Virus Vaccine, rWN/DEN4&Dgr;30, Is Well Tolerated and Immunogenic in Flavivirus-Naive Older Adult Volunteers"
},
{
"docid": "13469921",
"text": "Recent cross-sectional analyses of HIV-1+ plasmas have indicated that broadly cross-reactive neutralizing antibody responses are developed by 10%-30% of HIV-1+ subjects. The timing of the initial development of such anti-viral responses is unknown. It is also unknown whether the emergence of these responses coincides with the appearance of antibody specificities to a single or multiple regions of the viral envelope glycoprotein (Env). Here we analyzed the cross-neutralizing antibody responses in longitudinal plasmas collected soon after and up to seven years after HIV-1 infection. We find that anti-HIV-1 cross-neutralizing antibody responses first become evident on average at 2.5 years and, in rare cases, as early as 1 year following infection. If cross-neutralizing antibody responses do not develop during the first 2-3 years of infection, they most likely will not do so subsequently. Our results indicate a potential link between the development of cross-neutralizing antibody responses and specific activation markers on T cells, and with plasma viremia levels. The earliest cross-neutralizing antibody response targets a limited number of Env regions, primarily the CD4-binding site and epitopes that are not present on monomeric Env, but on the virion-associated trimeric Env form. In contrast, the neutralizing activities of plasmas from subjects that did not develop cross-neutralizing antibody responses target epitopes on monomeric gp120 other than the CD4-BS. Our study provides information that is not only relevant to better understanding the interaction of the human immune system with HIV but may guide the development of effective immunization protocols. Since antibodies to complex epitopes that are present on the virion-associated envelope spike appear to be key components of earliest cross-neutralizing activities of HIV-1+ plasmas, then emphasis should be made to elicit similar antibodies by vaccination.",
"title": "Characteristics of the Earliest Cross-Neutralizing Antibody Response to HIV-1"
},
{
"docid": "152245",
"text": "The genomic RNA of an alphavirus encodes four different nonstructural proteins, nsP1, nsP2, nsP3, and nsP4. The polyprotein P123 is produced when translation terminates at an opal termination codon between nsP3 and nsP4. The polyprotein P1234 is produced when translational readthrough occurs or when the opal termination codon has been replaced by a sense codon in the alphavirus genome. Evolutionary pressures appear to have maintained genomic sequences encoding both a stop codon (opal) and an open reading frame (arginine) as a general feature of the O'nyong-nyong virus (ONNV) genome, indicating that both are required at some point. Alternate replication of ONNVs in both vertebrate and invertebrate hosts may determine predominance of a particular codon at this locus in the viral quasispecies. However, no systematic study has previously tested this hypothesis in whole animals. We report here the results of the first study to investigate in a natural mosquito host the functional significance of the opal stop codon in an alphavirus genome. We used a full-length cDNA clone of ONNV to construct a series of mutants in which the arginine between nsP3 and nsP4 was replaced with an opal, ochre, or amber stop codon. The presence of an opal stop codon upstream of nsP4 nearly doubled (75.5%) the infectivity of ONNV over that of virus possessing a codon for the amino acid arginine at the corresponding position (39.8%). Although the frequency with which the opal virus disseminated from the mosquito midgut did not differ significantly from that of the arginine virus on days 8 and 10, dissemination did began earlier in mosquitoes infected with the opal virus. Although a clear fitness advantage is provided to ONNV by the presence of an opal codon between nsP3 and nsP4 in Anopheles gambiae, sequence analysis of ONNV RNA extracted from mosquito bodies and heads indicated codon usage at this position corresponded with that of the virus administered in the blood meal. These results suggest that while selection of ONNV variants is occurring, de novo mutation at the position between nsP3 and nsP4 does not readily occur in the mosquito. Taken together, these results suggest that the primary fitness advantage provided to ONNV by the presence of an opal codon between nsP3 and nsP4 is related to mosquito infectivity.",
"title": "Effects of an opal termination codon preceding the nsP4 gene sequence in the O'Nyong-Nyong virus genome on Anopheles gambiae infectivity."
},
{
"docid": "4373433",
"text": "Broadly neutralizing antibodies against highly variable viral pathogens are much sought after to treat or protect against global circulating viruses. Here we probed the neutralizing antibody repertoires of four human immunodeficiency virus (HIV)-infected donors with remarkably broad and potent neutralizing responses and rescued 17 new monoclonal antibodies that neutralize broadly across clades. Many of the new monoclonal antibodies are almost tenfold more potent than the recently described PG9, PG16 and VRC01 broadly neutralizing monoclonal antibodies and 100-fold more potent than the original prototype HIV broadly neutralizing monoclonal antibodies. The monoclonal antibodies largely recapitulate the neutralization breadth found in the corresponding donor serum and many recognize novel epitopes on envelope (Env) glycoprotein gp120, illuminating new targets for vaccine design. Analysis of neutralization by the full complement of anti-HIV broadly neutralizing monoclonal antibodies now available reveals that certain combinations of antibodies should offer markedly more favourable coverage of the enormous diversity of global circulating viruses than others and these combinations might be sought in active or passive immunization regimes. Overall, the isolation of multiple HIV broadly neutralizing monoclonal antibodies from several donors that, in aggregate, provide broad coverage at low concentrations is a highly positive indicator for the eventual design of an effective antibody-based HIV vaccine.",
"title": "Broad neutralization coverage of HIV by multiple highly potent antibodies"
},
{
"docid": "21150010",
"text": "Metastatic ovarian cancer is the leading cause of death among women with gynecologic malignancies in the United States. The lack of effective treatment for patients with advanced ovarian cancer warrants development of innovative therapies. Cancer therapy using oncolytic viruses represents a promising new approach for controlling tumors. Vaccinia virus has been shown to preferentially infect tumor cells but not normal tissue. However, oncolytic therapy using recombinant viruses faces the limitation of viral clearance due to generation of neutralizing antibodies. In the current study, we found that cyclooxygenase-2 (Cox-2) inhibitors circumvented this limitation, enabling repeated administration of vaccinia virus without losing infectivity. We quantified the antivaccinia antibody response using enzyme-linked immunosorbent assay (ELISA) and neutralization assays to show that treatment of Cox-2 inhibitors inhibited the generation of neutralizing antibodies. Furthermore, we showed that combination treatment of Cox-2 inhibitors with vaccinia virus was more effective that either treatment alone in treating MOSEC/luc tumor-bearing mice. Thus, the combination of Cox-2 inhibitors and vaccinia virus represents a potential innovative approach to controlling ovarian tumors.",
"title": "Treatment with cyclooxygenase-2 inhibitors enables repeated administration of vaccinia virus for control of ovarian cancer."
},
{
"docid": "26038789",
"text": "3BNC117 is a broad and potent neutralizing antibody to HIV-1 that targets the CD4 binding site on the viral envelope spike. When administered passively, this antibody can prevent infection in animal models and suppress viremia in HIV-1–infected individuals. Here we report that HIV-1 immunotherapy with a single injection of 3BNC117 affects host antibody responses in viremic individuals. In comparison to untreated controls that showed little change in their neutralizing activity over a 6-month period, 3BNC117 infusion significantly improved neutralizing responses to heterologous tier 2 viruses in nearly all study participants. We conclude that 3BNC117-mediated immunotherapy enhances host humoral immunity to HIV-1.",
"title": "HIV-1 therapy with monoclonal antibody 3BNC117 elicits host immune responses against HIV-1"
},
{
"docid": "12885341",
"text": "West Nile virus (WNV) is the most common arthropod-borne flavivirus in the United States; however, the vector ligand(s) that participate in infection are not known. We now show that an Aedes aegypti C-type lectin, mosGCTL-1, is induced by WNV, interacts with WNV in a calcium-dependent manner, and facilitates infection in vivo and in vitro. A mosquito homolog of human CD45 in A. aegypti, designated mosPTP-1, recruits mosGCTL-1 to enable viral attachment to cells and to enhance viral entry. In vivo experiments show that mosGCTL-1 and mosPTP-1 function as part of the same pathway and are critical for WNV infection of mosquitoes. A similar phenomenon was also observed in Culex quinquefasciatus, a natural vector of WNV, further demonstrating that these genes participate in WNV infection. During the mosquito blood-feeding process, WNV infection was blocked in vivo with mosGCTL-1 antibodies. A molecular understanding of flaviviral-arthropod interactions may lead to strategies to control viral dissemination in nature.",
"title": "A C-Type Lectin Collaborates with a CD45 Phosphatase Homolog to Facilitate West Nile Virus Infection of Mosquitoes"
},
{
"docid": "15237660",
"text": "BACKGROUND Long-lasting insecticide treated nets (LLINs) and indoor residual house spraying (IRS) are the main interventions for the control of malaria vectors in Zanzibar. The aim of the present study was to assess the susceptibility status of malaria vectors against the insecticides used for LLINs and IRS and to determine the durability and efficacy of LLINs on the island. METHODS Mosquitoes were sampled from Pemba and Unguja islands in 2010-2011 for use in WHO susceptibility tests. One hundred and fifty LLINs were collected from households on Unguja, their physical state was recorded and then tested for efficacy as well as total insecticide content. RESULTS Species identification revealed that over 90% of the Anopheles gambiae complex was An. arabiensis with a small number of An. gambiae s.s. and An. merus being present. Susceptibility tests showed that An. arabiensis on Pemba was resistant to the pyrethroids used for LLINs and IRS. Mosquitoes from Unguja Island, however, were fully susceptible to all pyrethroids tested. A physical examination of 150 LLINs showed that two thirds were damaged after only three years in use. All used nets had a significantly lower (p < 0.001) mean permethrin concentration of 791.6 mg/m2 compared with 944.2 mg/m2 for new ones. Their efficacy decreased significantly against both susceptible An. gambiae s.s. colony mosquitoes and wild-type mosquitoes from Pemba after just six washes (p < 0.001). CONCLUSION The sustainability of the gains achieved in malaria control in Zanzibar is seriously threatened by the resistance of malaria vectors to pyrethroids and the short-lived efficacy of LLINs. This study has revealed that even in relatively well-resourced and logistically manageable places like Zanzibar, malaria elimination is going to be difficult to achieve with the current control measures.",
"title": "Challenges for malaria elimination in Zanzibar: pyrethroid resistance in malaria vectors and poor performance of long-lasting insecticide nets"
},
{
"docid": "15488881",
"text": "Humoral immunity depends on both rapid and long-term antibody production against invading pathogens. This is achieved by the generation of spatially distinct extrafollicular plasmablast and follicular germinal center (GC) B cell populations, but the signals that guide responding B cells to these alternative compartments have not been fully elucidated. Here, we show that expression of the orphan G protein-coupled receptor Epstein-Barr virus-induced gene 2 (EBI2, also known as GPR183) by activated B cells was essential for their movement to extrafollicular sites and induction of early plasmablast responses. Conversely, downregulation of EBI2 enabled B cells to access the center of follicles and promoted efficient GC formation. EBI2 therefore provides a previously uncharacterized dimension to B cell migration that is crucial for coordinating rapid versus long-term antibody responses.",
"title": "Guidance of B cells by the orphan G protein-coupled receptor EBI2 shapes humoral immune responses."
},
{
"docid": "10494012",
"text": "Amodel that explains both the origin and sporadic nature of cancer argues that cancer cells are a chance result of events that cause genomic and epigenetic variability. The prevailing view is that these events are mutations that affect chromosome segregation or stability. However, genomic and epigenetic variability is also triggered by cell fusion, which is often caused by viruses. Yet, cells fused by viruses are considered harmless because they die. We provide evidence that a primate virus uses both viral and exosomal proteins involved in cell fusion to produce transformed proliferating human cells. Although normal cells indeed fail to proliferate after fusion, expression of an oncogene or a mutated tumor suppressor p53 in just one of the fusion partners is sufficient to produce heterogeneous progeny. We also show that this virus can produce viable oncogenically transformed cells by fusing cells that are otherwise destined to die. Therefore, we argue that viruses can contribute to carcinogenesis by fusing cells.",
"title": "A primate virus generates transformed human cells by fusion"
},
{
"docid": "16939583",
"text": "Variation in cerebral cortex size and complexity is thought to contribute to differences in cognitive ability between humans and other animals. Here we compare cortical progenitor cell output in humans and three nonhuman primates using directed differentiation of pluripotent stem cells (PSCs) in adherent two-dimensional (2D) and organoid three-dimensional (3D) culture systems. Clonal lineage analysis showed that primate cortical progenitors proliferate for a protracted period of time, during which they generate early-born neurons, in contrast to rodents, where this expansion phase largely ceases before neurogenesis begins. The extent of this additional cortical progenitor expansion differs among primates, leading to differences in the number of neurons generated by each progenitor cell. We found that this mechanism for controlling cortical size is regulated cell autonomously in culture, suggesting that primate cerebral cortex size is regulated at least in part at the level of individual cortical progenitor cell clonal output.",
"title": "2D and 3D Stem Cell Models of Primate Cortical Development Identify Species-Specific Differences in Progenitor Behavior Contributing to Brain Size."
},
{
"docid": "45244537",
"text": "Evaluation of testicular functions (production of sperm and androgens) is an important aspect of preclinical safety assessment and testicular toxicity is comparatively far more common than ovarian toxicity. This chapter focuses (1) on the histological sequelae of disturbed reproductive endocrinology in rat, dog and nonhuman primates and (2) provides a review of our current understanding of the roles of gonadotropins and androgens. The response of the rodent testis to endocrine disturbances is clearly different from that of dog and primates with different germ cell types and spermatogenic stages being affected initially and also that the end-stage spermatogenic involution is more pronounced in dog and primates compared to rodents. Luteinizing hormone (LH)/testosterone and follicle-stimulating hormone (FSH) are the pivotal endocrine factors controlling testicular functions. The relative importance of either hormone is somewhat different between rodents and primates. Generally, however, both LH/testosterone and FSH are necessary for quantitatively normal spermatogenesis, at least in non-seasonal species.",
"title": "Endocrine control of spermatogenesis: Role of FSH and LH/ testosterone."
},
{
"docid": "19327364",
"text": "Sera from 526 Old-World monkeys and apes, representing 50 species and 20 genera and living in US zoos and vivaria, were screened for antibodies to HTLV-I, HTLV-III/LAV, and simian-AIDS retrovirus, type I (SRV-I). Sera were screened initially by ELISA, and ELISA-positive sera, as well as ELISA-negative sera from cage contacts, were further tested by Western blotting. A large number of false-positive and a small number of false-negative ELISA sera were identified. Although most true positive reactions were directed to a single retrovirus, a number of individuals from 4 species were positive for more than one retrovirus. Specific seroreactivity to HTLV-I was found in 39/526 (7%) animals of 15 species. True positive reactions to SRV-I were found in 21/516 (4%) animals, including talapoins and 2 species of macaques. Specific serologic reactions to HTLV-III/LAV were detected in 23/526 (4%) monkeys. Many of the HTLV-III/LAV seropositive animals were from one mixed-species zoo exhibit, containing sooty mangabeys, mandrills, Kolb's guenons, and talapoins. A type D virus was isolated from the blood of 3/10 SRV-I antibody-positive Tonkeana macaques, but from none of 11 seropositive talapoins. A lentivirus was isolated from the blood of 4/7 HTLV-III/LAV seropositive sooty mangabeys, but not from seropositive talapoins in the same exhibit or from 2 seropositive colobus from another zoo. The sooty mangabey lentivirus produced generalized lymphadenopathy, leukopenia, and decreased levels of T4 lymphocytes in 2 experimentally infected rhesus macaques.",
"title": "Seroepidemiologic survey of captive Old-World primates for antibodies to human and simian retroviruses, and isolation of a lentivirus from sooty mangabeys (Cercocebus atys)."
},
{
"docid": "34287602",
"text": "Intrahost genetic diversity was analysed in naturally infected mosquitoes and birds to determine whether West Nile virus (WNV) exists in nature as a quasispecies and to quantify selective pressures within and between hosts. WNV was sampled from ten infected birds and ten infected mosquito pools collected on Long Island, NY, USA, during the peak of the 2003 WNV transmission season. A 1938 nt fragment comprising the 3' 1159 nt of the WNV envelope (E) coding region and the 5' 779 nt of the non-structural protein 1 (NS1) coding region was amplified and cloned and 20 clones per specimen were sequenced. Results from this analysis demonstrate that WNV infections are derived from a genetically diverse population of genomes in nature. The mean nucleotide diversity was 0.016 % within individual specimens and the mean percentage of clones that differed from the consensus sequence was 19.5 %. WNV sequences in mosquitoes were significantly more genetically diverse than WNV in birds. No host-dependent bias for particular types of mutations was observed and estimates of genetic diversity did not differ significantly between E and NS1 coding sequences. Non-consensus clones obtained from two avian specimens had highly similar genetic signatures, providing preliminary evidence that WNV genetic diversity may be maintained throughout the enzootic transmission cycle, rather than arising independently during each infection. Evidence of purifying selection was obtained from both intra- and interhost WNV populations. Combined, these data support the observation that WNV populations may be structured as a quasispecies and document strong purifying natural selection in WNV populations.",
"title": "Genetic variation in West Nile virus from naturally infected mosquitoes and birds suggests quasispecies structure and strong purifying selection."
},
{
"docid": "1970884",
"text": "Viruses that replicate in the cytoplasm cannot access the host nuclear capping machinery. These viruses have evolved viral methyltransferase(s) to methylate N-7 and 2'-O cap of their RNA; alternatively, they \"snatch\" host mRNA cap to form the 5' end of viral RNA. The function of 2'-O methylation of viral RNA cap is to mimic cellular mRNA and to evade host innate immune restriction. A cytoplasmic virus defective in 2'-O methylation is replicative, but its viral RNA lacks 2'-O methylation and is recognized and eliminated by the host immune response. Such a mutant virus could be rationally designed as a live attenuated vaccine. Here, we use Japanese encephalitis virus (JEV), an important mosquito-borne flavivirus, to prove this novel vaccine concept. We show that JEV methyltransferase is responsible for both N-7 and 2'-O cap methylations as well as evasion of host innate immune response. Recombinant virus completely defective in 2'-O methylation was stable in cell culture after being passaged for >30 days. The mutant virus was attenuated in mice, elicited robust humoral and cellular immune responses, and retained the engineered mutation in vivo. A single dose of immunization induced full protection against lethal challenge with JEV strains in mice. Mechanistically, the attenuation phenotype was attributed to the enhanced sensitivity of the mutant virus to the antiviral effects of interferon and IFIT proteins. Collectively, the results demonstrate the feasibility of using 2'-O methylation-defective virus as a vaccine approach; this vaccine approach should be applicable to other flaviviruses and nonflaviviruses that encode their own viral 2'-O methyltransferases.",
"title": "Rational design of a flavivirus vaccine by abolishing viral RNA 2'-O methylation."
},
{
"docid": "9539248",
"text": "Mosquito-borne viruses cause significant levels of morbidity and mortality in humans and domesticated animals. Maintenance of mosquito-borne viruses in nature requires a biological transmission cycle that involves alternating virus replication in a susceptible vertebrate and mosquito host. Although the vertebrate infection is acute and often associated with disease, continual transmission of these viruses in nature depends on the establishment of a persistent, nonpathogenic infection in the mosquito vector. An antiviral RNAi response has been shown to limit the replication of RNA viruses in flies. However, the importance of the RNAi pathway as an antiviral defense in mammals is unclear. Differences in the immune responses of mammals and mosquitoes may explain why these viruses are not generally associated with pathology in the invertebrate host. We identified virus-derived small interfering RNAs (viRNAs), 21 nt in length, in Aedes aegypti infected with the mosquito-borne virus, Sindbis (SINV). viRNAs had an asymmetric distribution that spanned the length of the SINV genome. To determine the role of viRNAs in controlling pathogenic potential, mosquitoes were infected with recombinant alphaviruses expressing suppressors of RNA silencing. Decreased survival was observed in mosquitoes in which the accumulation of viRNAs was suppressed. These results suggest that an exogenous siRNA pathway is essential to the survival of mosquitoes infected with alphaviruses and, thus, the maintenance of these viruses in nature.",
"title": "Alphavirus-derived small RNAs modulate pathogenesis in disease vector mosquitoes."
},
{
"docid": "22705234",
"text": "The African green monkey (AGM) is one of many African species endemically infected with simian immunodeficiency virus (SIV). Like the other natural hosts, AGMs do not succumb to AIDS and understanding the basis for this resistance to disease progression would be of enormous theoretical and practical importance. Early efforts by our group that concentrated on identifying immune mechanisms presumed to keep the virus under control failed to find any obvious candidates. The presumption of virus control was invalidated by the finding that SIVagm replicates in AGMs with the same vigor as HIV-1 does in humans. Focus therefore shifted to identifying possible immunopathologic features present in disease susceptible hosts but absent in the AGM natural host. The apparent immunologic tolerance of AGMs to the SIVagm core protein led to the development of a hypothesis implicating anti-Gag antibodies in the formation of immune complexes, virus trapping in the lymph nodes and immune dysfunction. The idea proved difficult to test in vivo and present work focuses on the possibility that Gag tolerance at the T-cell level plays an important role in preventing the catastrophic demise of the immune system characteristic of immunodeficiency virus infection of the heterologous primate host.",
"title": "The role of the immune response during SIVagm infection of the African green monkey natural host."
},
{
"docid": "10450300",
"text": "Human cytomegalovirus (HCMV) is a widely prevalent human herpesvirus, which, after primary infection, persists in the host for life. In healthy individuals, the virus is well controlled by the HCMV-specific T cell response. A key feature of this persistence, in the face of a normally robust host immune response, is the establishment of viral latency. In contrast to lytic infection, which is characterised by extensive viral gene expression and virus production, long-term latency in cells of the myeloid lineage is characterised by highly restricted expression of viral genes, including UL138 and LUNA. Here we report that both UL138 and LUNA-specific T cells were detectable directly ex vivo in healthy HCMV seropositive subjects and that this response is principally CD4⁺ T cell mediated. These UL138-specific CD4⁺ T cells are able to mediate MHC class II restricted cytotoxicity and, importantly, show IFNγ effector function in the context of both lytic and latent infection. Furthermore, in contrast to CDCD4⁺ T cells specific to antigens expressed solely during lytic infection, both the UL138 and LUNA-specific CD4⁺ T cell responses included CD4⁺ T cells that secreted the immunosuppressive cytokine cIL-10. We also show that cIL-10 expressing CD4⁺ T-cells are directed against latently expressed US28 and UL111A. Taken together, our data show that latency-associated gene products of HCMV generate CD4⁺ T cell responses in vivo, which are able to elicit effector function in response to both lytic and latently infected cells. Importantly and in contrast to CD4⁺ T cell populations, which recognise antigens solely expressed during lytic infection, include a subset of cells that secrete the immunosuppressive cytokine cIL-10. This suggests that HCMV skews the T cell responses to latency-associated antigens to one that is overall suppressive in order to sustain latent carriage in vivo.",
"title": "Human Cytomegalovirus Latency-Associated Proteins Elicit Immune-Suppressive IL-10 Producing CD4+ T Cells"
},
{
"docid": "32170702",
"text": "Maintenance of hematopoietic stem cells (HSCs) depends on interaction with their niche. Here we show that the long-term (LT)-HSCs expressing the thrombopoietin (THPO) receptor, MPL, are a quiescent population in adult bone marrow (BM) and are closely associated with THPO-producing osteoblastic cells. THPO/MPL signaling upregulated beta1-integrin and cyclin-dependent kinase inhibitors in HSCs. Furthermore, inhibition and stimulation of THPO/MPL pathway by treatments with anti-MPL neutralizing antibody, AMM2, and with THPO showed reciprocal regulation of quiescence of LT-HSC. AMM2 treatment reduced the number of quiescent LT-HSCs and allowed exogenous HSC engraftment without irradiation. By contrast, exogenous THPO transiently increased quiescent HSC population and subsequently induced HSC proliferation in vivo. Altogether, these observations suggest that THPO/MPL signaling plays a critical role of LT-HSC regulation in the osteoblastic niche.",
"title": "Thrombopoietin/MPL signaling regulates hematopoietic stem cell quiescence and interaction with the osteoblastic niche."
},
{
"docid": "24155601",
"text": "To systematically review clinical and preclinical data on hydroxyethyl starch (HES) tissue storage. MEDLINE (PubMed) was searched and abstracts were screened using defined criteria to identify articles containing original data on HES tissue accumulation. Forty-eight studies were included: 37 human studies with a total of 635 patients and 11 animal studies. The most frequent indication for fluid infusion was surgery accounting for 282 patients (45.9 %). HES localization in skin was shown by 17 studies, in kidney by 12, in liver by 8, and in bone marrow by 5. Additional sites of HES deposition were lymph nodes, spleen, lung, pancreas, intestine, muscle, trophoblast, and placental stroma. Among major organs the highest measured tissue concentration of HES was in the kidney. HES uptake into intracellular vacuoles was observed by 30 min after infusion. Storage was cumulative, increasing in proportion to dose, although in 15 % of patients storage and associated symptoms were demonstrated at the lowest cumulative doses (0.4 g kg−1). Some HES deposits were extremely long-lasting, persisting for 8 years or more in skin and 10 years in kidney. Pruritus associated with HES storage was described in 17 studies and renal dysfunction in ten studies. In one included randomized trial, HES infusion produced osmotic nephrosis-like lesions indicative of HES storage (p = 0.01) and also increased the need for renal replacement therapy (odds ratio, 9.50; 95 % confidence interval, 1.09–82.7; p = 0.02). The tissue distribution of HES was generally similar in animals and humans. Tissue storage of HES is widespread, rapid, cumulative, frequently long-lasting, and potentially harmful.",
"title": "Accumulation of hydroxyethyl starch in human and animal tissues: a systematic review"
},
{
"docid": "2947124",
"text": "During persistent viral infections, chronic immune activation, negative immune regulator expression, an elevated interferon signature, and lymphoid tissue destruction correlate with disease progression. We demonstrated that blockade of type I interferon (IFN-I) signaling using an IFN-I receptor neutralizing antibody reduced immune system activation, decreased expression of negative immune regulatory molecules, and restored lymphoid architecture in mice persistently infected with lymphocytic choriomeningitis virus. IFN-I blockade before and after establishment of persistent virus infection resulted in enhanced virus clearance and was CD4 T cell-dependent. Hence, we demonstrate a direct causal link between IFN-I signaling, immune activation, negative immune regulator expression, lymphoid tissue disorganization, and virus persistence. Our results suggest that therapies targeting IFN-I may help control persistent virus infections.",
"title": "Persistent LCMV infection is controlled by blockade of type I interferon signaling."
},
{
"docid": "4421578",
"text": "Characterization of human monoclonal antibodies is providing considerable insight into mechanisms of broad HIV-1 neutralization. Here we report an HIV-1 gp41 membrane-proximal external region (MPER)-specific antibody, named 10E8, which neutralizes ∼98% of tested viruses. An analysis of sera from 78 healthy HIV-1-infected donors demonstrated that 27% contained MPER-specific antibodies and 8% contained 10E8-like specificities. In contrast to other neutralizing MPER antibodies, 10E8 did not bind phospholipids, was not autoreactive, and bound cell-surface envelope. The structure of 10E8 in complex with the complete MPER revealed a site of vulnerability comprising a narrow stretch of highly conserved gp41-hydrophobic residues and a critical arginine or lysine just before the transmembrane region. Analysis of resistant HIV-1 variants confirmed the importance of these residues for neutralization. The highly conserved MPER is a target of potent, non-self-reactive neutralizing antibodies, suggesting that HIV-1 vaccines should aim to induce antibodies to this region of HIV-1 envelope glycoprotein.",
"title": "Broad and potent neutralization of HIV-1 by a gp41-specific human antibody"
}
] |
PLAIN-317
|
Inflammation, Diet, and "Vitamin S"
|
[
{
"docid": "MED-735",
"text": "BACKGROUND: Aspirin is valuable for preventing vascular events, but information about ulcer frequency is necessary to inform risk-benefit decisions in individual patients. AIM: To determine ulcer prevalence and incidence in a population representative of those given aspirin therapy and evaluate risk predictors. METHODS: Patients taking aspirin 75-325 mg daily were recruited from four countries. Exclusions included use of gastroprotectant drugs or other non-steroidal anti-inflammatory drugs. We measured point prevalence of endoscopic ulcers, after quantitating dyspeptic symptoms. Incidence was assessed 3 months later in those eligible to continue (no baseline ulcer or reason for gastroprotectants). RESULTS: In 187 patients, ulcer prevalence was 11% [95% confidence interval (CI) 6.3-15.1%]. Only 20% had dyspeptic symptoms, not significantly different from patients without ulcer. Ulcer incidence in 113 patients followed for 3 months was 7% (95% CI 2.4-11.8%). Helicobacter pylori infection increased the risk of a duodenal ulcer [odds ratio (OR) 18.5, 95% CI 2.3-149.4], as did age >70 for ulcers in stomach and duodenum combined (OR 3.3, 95% CI 1.3-8.7). CONCLUSIONS: Gastroduodenal ulcers are found in one in 10 patients taking low-dose aspirin, and most are asymptomatic; this needs considering when discussing risks/benefits with patients. Risk factors include older age and H. pylori (for duodenal ulcer).",
"title": "Prevalence and incidence of gastroduodenal ulcers during treatment with vascular protective doses of aspirin."
},
{
"docid": "MED-4719",
"text": "Among the many known health benefits of tea catechins count anti-inflammatory and neuroprotective activities, as well as effects on the regulation of food intake. Here we address cannabimimetic bioactivity of catechin derivatives occurring in tea leaves as a possible cellular effector of these functionalities. Competitive radioligand binding assays using recombinant human cannabinoid receptors expressed in Chem-1 and CHO cells identified (-)-epigallocatechin-3-O-gallate, EGCG (K(i)=33.6 microM), (-)-epigallocatechin, EGC (K(i)=35.7 microM), and (-)-epicatechin-3-O-gallate, ECG (K(i)=47.3 microM) as ligands with moderate affinity for type 1 cannabinoid receptors, CB1. Binding to CB2 was weaker with inhibition constants exceeding 50 microM for EGC and ECG. The epimers (+)-catechin and (-)-epicatechin exhibited negligible affinities for both CB1 and CB2. It can be concluded that central nervous cannabinoid receptors may be targeted by selected tea catechins but signaling via peripheral type receptors is less likely to play a major role in vivo.",
"title": "Tea catechins' affinity for human cannabinoid receptors."
},
{
"docid": "MED-4628",
"text": "BACKGROUND & AIMS: Dietary arachidonic acid, an n-6 polyunsaturated fatty acid (n-6 PUFA), might be involved in the etiology of ulcerative colitis (UC). We performed a prospective cohort study to determine whether high levels of arachidonic acid in adipose tissue samples (which reflects dietary intake) are associated with UC. METHODS: We analyzed data collected from 57,053 men and women in the EPIC-Denmark Prospective Cohort Study from 1993 to 1997. Adipose tissue biopsy samples were collected from gluteal regions at the beginning of the study, the cohort was monitored over subsequent years, and participants who developed UC were identified. A subcohort of 2510 randomly selected participants were used as controls. Concentrations of arachidonic acid were measured in adipose tissue samples. In the analysis, arachidonic acid levels were divided into quartiles; relative risks (RR) were calculated and adjusted for smoking, use of aspirin and nonsteroidal anti-inflammatory drugs, and levels of n-3 PUFAs. RESULTS: A total of 34 subjects (56% men) developed incident UC at a median age of 58.8 years (range, 50.0-69.0 years). Those in the highest quartile for arachidonic acid concentrations in adipose tissue had an RR for UC of 4.16 (95% confidence interval [CI]: 1.56-11.04); a trend per 0.1% increase in arachidonic acid of 1.77 in RR was observed (95% CI: 1.38-2.27). The fraction attributed the highest levels of arachidonic acid was 40.3%. CONCLUSIONS: Individuals with the highest relative concentrations of arachidonic acid in adipose tissue have a significantly greater risk of developing UC. Dietary modifications might therefore prevent UC or reduce disease symptoms. Copyright © 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.",
"title": "An association between dietary arachidonic acid, measured in adipose tissue, and ulcerative colitis."
},
{
"docid": "MED-4631",
"text": "BACKGROUND: Patients with rheumatoid arthritis (RA) improve on a vegetarian diet or supplementation with fish oil. We investigated the effects of both dietary measures, alone and in combination, on inflammation, fatty acid composition of erythrocyte lipids, eicosanoids, and cytokine biosynthesis in patients with RA. METHODS: Sixty-eight patients with definitive RA were matched into two groups of 34 subjects each. One group was observed for 8 months on a normal western diet (WD) and the other on an anti-inflammatory diet (AID) providing an arachidonic acid intake of less than 90 mg/day. Patients in both groups were allocated to receive placebo or fish oil capsules (30 mg/kg body weight) for 3 months in a double-blind crossover study with a 2-month washout period between treatments. Clinical examination and routine laboratory findings were evaluated every month, and erythrocyte fatty acids, eicosanoids, and cytokines were evaluated before and after each 3-month experimental period. RESULTS: Sixty patients completed the study. In AID patients, but not in WD patients, the numbers of tender and swollen joints decreased by 14% during placebo treatment. In AID patients, as compared to WD patients, fish oil led to a significant reduction in the numbers of tender (28% vs 11%) and swollen (34% vs 22%) joints (P<0.01). Compared to baseline levels, higher enrichment of eicosapentaenoic acid in erythrocyte lipids (244% vs 217%) and lower formation of leukotriene B(4) (34% vs 8%, P>0.01), 11-dehydro-thromboxane B(2) (15% vs 10%, P<0.05), and prostaglandin metabolites (21% vs 16%, P<0.003) were found in AID patients, especially when fish oil was given during months 6-8 of the experiment. CONCLUSION: A diet low in arachidonic acid ameliorates clinical signs of inflammation in patients with RA and augments the beneficial effect of fish oil supplementation.",
"title": "Anti-inflammatory effects of a low arachidonic acid diet and fish oil in patients with rheumatoid arthritis."
},
{
"docid": "MED-5342",
"text": "Background The physical health status of vegetarians has been extensively reported, but there is limited research regarding the mental health status of vegetarians, particularly with regard to mood. Vegetarian diets exclude fish, the major dietary source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), critical regulators of brain cell structure and function. Omnivorous diets low in EPA and DHA are linked to impaired mood states in observational and experimental studies. Methods We examined associations between mood state and polyunsaturated fatty acid intake as a result of adherence to a vegetarian or omnivorous diet in a cross-sectional study of 138 healthy Seventh Day Adventist men and women residing in the Southwest. Participants completed a quantitative food frequency questionnaire, Depression Anxiety Stress Scale (DASS), and Profile of Mood States (POMS) questionnaires. Results Vegetarians (VEG:n = 60) reported significantly less negative emotion than omnivores (OMN:n = 78) as measured by both mean total DASS and POMS scores (8.32 ± 0.88 vs 17.51 ± 1.88, p = .000 and 0.10 ± 1.99 vs 15.33 ± 3.10, p = .007, respectively). VEG reported significantly lower mean intakes of EPA (p < .001), DHA (p < .001), as well as the omega-6 fatty acid, arachidonic acid (AA; p < .001), and reported higher mean intakes of shorter-chain α-linolenic acid (p < .001) and linoleic acid (p < .001) than OMN. Mean total DASS and POMS scores were positively related to mean intakes of EPA (p < 0.05), DHA (p < 0.05), and AA (p < 0.05), and inversely related to intakes of ALA (p < 0.05), and LA (p < 0.05), indicating that participants with low intakes of EPA, DHA, and AA and high intakes of ALA and LA had better mood. Conclusions The vegetarian diet profile does not appear to adversely affect mood despite low intake of long-chain omega-3 fatty acids.",
"title": "Vegetarian diets are associated with healthy mood states: a cross-sectional study in Seventh Day Adventist adults"
},
{
"docid": "MED-4629",
"text": "In a controlled, single blind clinical trial we have demonstrated recently a beneficial effect of fasting and vegetarian diet in RA. In the present study we compared 53 patients who participated in this clinical trial with 71 other RA patients with regard to some psychological parameters. The patients who participated in the clinical trial differed significantly from other RA patients. Firstly, they had a higher internal score and a lower chance score on the Multi-dimensional Health Locus of Control Scale (MHLCS). Secondly, their belief in the effect of ordinary medical treatment, evaluated by a 10-cm visual analogue scale, was lower, and their belief in the effect of 'alternative', unconventional forms of treatment was higher. Of the patients who were randomized to a vegetarian diet, there was no significant difference between diet responders and diet non-responders with regard to the MHLCS scores. But, diet responders had a significantly lower belief in the effect of ordinary medical treatment compared with diet non-responders. The psychological distress imposed on the patients by changing from an omnivorous diet to a vegetarian diet was monitored during the clinical trial by means of the General Health Questionnaire. Throughout the clinical trial, this variable favoured the vegetarians compared with the omnivorous and the diet responders vs the diet non-responders. We conclude, firstly, that patients with certain psychological characteristics were selected to the clinical trial; secondly, that the MHLCS scores could not explain the clinical improvement, but it may have been influenced by the patients' beliefs in ordinary and 'alternative' forms of treatment; and thirdly, that dietary treatment decreased psychological distress.",
"title": "Vegetarian diet for patients with rheumatoid arthritis: can the clinical effects be explained by the psychological characteristics of the patients?"
},
{
"docid": "MED-4630",
"text": "Arachidonic acid (AA)-derived eicosanoids belong to a complex family of lipid mediators that regulate a wide variety of physiological responses and pathological processes. They are produced by various cell types through distinct enzymatic pathways and act on target cells via specific G-protein-coupled receptors. Although originally recognized for their capacity to elicit biological responses such as vascular homeostasis, protection of the gastric mucosa and platelet aggregation, eicosanoids are now understood to regulate immunopathological processes ranging from inflammatory responses to chronic tissue remodelling, cancer, asthma, rheumatoid arthritis and autoimmune disorders. Here, we review the major properties of eicosanoids and their expanding roles in biology and medicine.",
"title": "Arachidonic-acid-derived eicosanoids: roles in biology and immunopathology."
}
] |
[
{
"docid": "MED-2452",
"text": "A role for diet in the pathophysiology of asthma may be mediated by altered immune or antioxidant activity with consequent effects on airway inflammation. We evaluated associations between several dietary factors assessed by a semiquantitative food frequency questionnaire, and incidence of asthma over a 10-yr period in 77,866 women 34 to 68 yr of age. Women in the highest quintile of vitamin E intake from diet, but not from supplements, had a risk of 0.53 (95% confidence interval [CI] = 0.33 to 0.86) compared with women in the lowest quintile. This relationship, however, was attenuated when the contribution from nuts, a major source of vitamin E in these data and a possible allergen, was removed (relative risk = 0.74 [0.50 to 1.10], p for trend = 0.007). Positive associations were found for vitamins C and E from supplements, but appeared to be explained by women at high risk of asthma initiating use of vitamin supplements prior to diagnosis. A nonsignificant inverse association with carotene intake was noted, but no clear relations with asthma were demonstrated for intake of linoleic acid or omega-3 fatty acids. These data suggest that antioxidant supplementation and intake of various fats during adulthood are not important determinants of asthma, although vitamin E from diet may have a modest protective effect.",
"title": "A prospective study of diet and adult-onset asthma."
},
{
"docid": "MED-5324",
"text": "Obesity has important health consequences, including elevating risk for heart disease, diabetes, and cancer. A high-fat diet is known to contribute to obesity. Little is known regarding the effect of a high-fat diet on pulmonary function, despite the dramatic increase in the prevalence of respiratory ailments (e.g., asthma). The purpose of our study was to determine whether a high-fat meal (HFM) would increase airway inflammation and decrease pulmonary function in healthy subjects. Pulmonary function tests (PFT) (forced expiratory volume in 1-s, forced vital capacity, forced expiratory flow at 25-75% of vital capacity) and exhaled nitric oxide (eNO; airway inflammation) were performed in 20 healthy (10 men, 10 women), inactive subjects (age 21.9 +/- 0.4 years) pre and 2 h post HFM (1 g fat/1 kg body weight; 74.2 +/- 4.1 g fat). Total cholesterol, triglycerides, and C-reactive protein (CRP; systemic inflammation) were determined via a venous blood sample pre and post HFM. Body composition was measured via dual energy X-ray absorptiometry. The HFM significantly increased total cholesterol by 4 +/- 1%, and triglycerides by 93 +/- 3%. ENO also increased (p < 0.05) due to the HFM by 19 +/- 1% (pre 17.2 +/- 1.6; post 20.6 +/- 1.7 ppb). ENO and triglycerides were significantly related at baseline and post-HFM (r = 0.82, 0.72 respectively). Despite the increased eNO, PFT or CRP did not change (p > 0.05) with the HFM. These results demonstrate that a HFM, which leads to significant increases in total cholesterol, and especially triglycerides, increases exhaled NO. This suggests that a high-fat diet may contribute to chronic inflammatory diseases of the airway and lung.",
"title": "Effects of a high-fat meal on pulmonary function in healthy subjects."
},
{
"docid": "MED-1788",
"text": "OBJECTIVE: To investigate whether lifestyle factors such as increased dietary intake of micronutrients reduce the risks of sperm DNA damage, and whether older men benefit more than younger men. DESIGN: Cross-sectional study design with equalized assignments into age groups. SETTING: National laboratory and university. PATIENT(S): Nonclinical group of 22-80-year-old nonsmoking men (n = 80) who reported no fertility problems. MAIN OUTCOME MEASURE(S): Sperm DNA damage measured by alkaline and neutral DNA electrophoresis (i.e., sperm Comet assay). RESULT(S): Sociodemographics, occupational exposures, medical and reproductive histories, and lifestyle habits were determined by questionnaire. The average daily dietary and supplement intake of micronutrients (vitamin C, vitamin E, b-carotene, zinc, and folate) was determined using the 100-item Modified Block Food Frequency Questionnaire (FFQ). Men with the highest intake of vitamin C had approximately 16% less sperm DNA damage (alkaline sperm Comet) than men with the lowest intake, with similar findings for vitamin E, folate, and zinc (but not β-carotene). Older men (>44 years) with the highest vitamin C intake had approximately 20% less sperm DNA damage compared with older men with the lowest intake, with similar findings for vitamin E and zinc. The older men with the highest intake of these micronutrients showed levels of sperm damage that were similar to those of the younger men. However, younger men (<44 years) did not benefit from higher intakes of the micronutrients surveyed. CONCLUSION(S): Men with higher dietary and supplement intake of certain micronutrients may produce sperm with less DNA damage, especially among older men. This raises the broader question of how lifestyle factors, including higher intakes of antioxidants and micronutrients, might protect somatic as well as germ cells against age-associated genomic damage. Copyright © 2012. Published by Elsevier Inc.",
"title": "Micronutrients intake is associated with improved sperm DNA quality in older men."
},
{
"docid": "MED-4850",
"text": "Plants are rich natural sources of antioxidants in addition to other nutrients. Interventions and cross sectional studies on subjects consuming uncooked vegan diet called living food (LF) have been carried out. We have clarified the efficacy of LF in rheumatoid diseases as an example of a health problem where inflammation is one of the main concerns. LF is an uncooked vegan diet and consists of berries, fruits, vegetables and roots, nuts, germinated seeds and sprouts, i.e. rich sources of carotenoids, vitamins C and E. The subjects eating LF showed highly increased levels of beta and alfa carotenes, lycopen and lutein in their sera. Also the increases of vitamin C and vitamin E (adjusted to cholesterol) were statistically significant. As the berry intake was 3-fold compared to controls the intake of polyphenolic compounds like quercetin, myricetin and kaempherol was much higher than in the omnivorous controls. The LF diet is rich in fibre, substrate of lignan production, and the urinary excretion of polyphenols like enterodiol and enterolactone as well as secoisolaricirecinol were much increased in subjects eating LF. The shift of fibromyalgic subjects to LF resulted in a decrease of their joint stiffness and pain as well as an improvement of their self-experienced health. The rheumatoid arthritis patients eating the LF diet also reported similar positive responses and the objective measures supported this finding. The improvement of rheumatoid arthritis was significantly correlated with the day-to-day fluctuation of subjective symptoms. In conclusion the rheumatoid patients subjectively benefited from the vegan diet rich in antioxidants, lactobacilli and fibre, and this was also seen in objective measures.",
"title": "Antioxidants in vegan diet and rheumatic disorders."
},
{
"docid": "MED-4878",
"text": "Background Telomere length reflects biological aging and may be influenced by environmental factors, including those that affect inflammatory processes. Objective With data from 840 white, black, and Hispanic adults from the Multi-Ethnic Study of Atherosclerosis, we studied cross-sectional associations between telomere length and dietary patterns and foods and beverages that were associated with markers of inflammation. Design Leukocyte telomere length was measured by quantitative polymerase chain reaction. Length was calculated as the amount of telomeric DNA (T) divided by the amount of a single-copy control DNA (S) (T/S ratio). Intake of whole grains, fruit and vegetables, low-fat dairy, nuts or seeds, nonfried fish, coffee, refined grains, fried foods, red meat, processed meat, and sugar-sweetened soda were computed with responses to a 120-item food-frequency questionnaire completed at baseline. Scores on 2 previously defined empirical dietary patterns were also computed for each participant. Results After adjustment for age, other demographics, lifestyle factors, and intakes of other foods or beverages, only processed meat intake was associated with telomere length. For every 1 serving/d greater intake of processed meat, the T/S ratio was 0.07 smaller (β ± SE: −0.07 ± 0.03, P = 0.006). Categorical analysis showed that participants consuming ≥1 serving of processed meat each week had 0.017 smaller T/S ratios than did nonconsumers. Other foods or beverages and the 2 dietary patterns were not associated with telomere length. Conclusions Processed meat intake showed an expected inverse association with telomere length, but other diet features did not show their expected associations.",
"title": "Dietary patterns, food groups, and telomere length in the Multi-Ethnic Study of Atherosclerosis (MESA)"
},
{
"docid": "MED-1834",
"text": "Observations of increasing allergy prevalence with decreasing distance from the Equator and positive associations with ambient ultraviolet radiation have contributed to a growing interest in the possible role of vitamin D in the etiology of allergy. The aims of this study were to describe any latitudinal variation in the prevalence of childhood allergy in Australia and to evaluate, in parallel, the individual associations between ultraviolet radiation (UVR)- and vitamin D-related measures and hayfever asthma and both conditions. Participants were population-based controls who took part in a multicenter case-control study, aged 18-61 yr and resident in one of four study regions ranging in latitude from 27°S to 43°S. Data were derived from a self-administered questionnaire, interview and examination by a research officer and biologic sampling. Latitude and longitude coordinates were geocoded from participants' residential locations and climatic data were linked to postcodes of current residence. Stored serum was analyzed for 25-hydroxyvitamin D concentrations and silicone rubber casts of the skin were used as an objective measure of cumulative actinic damage. There was an inverse latitude gradient for asthma (a 9% decrease per increasing degree of latitude); however, this pattern did not persist after adjusting for average daily temperature. There was no association between any of the UVR- or vitamin D-related measures and childhood asthma, but greater time in the sun in winter between the ages 6-15 yr was associated with an increase in the odds of having hayfever [adjusted odds ratios (OR) 1.29; 95% CI 1.01-1.63]. Oral supplementation with cod liver oil in childhood increased the odds of a history of having both asthma and hayfever (2.87; 1.00-8.32). Further investigation of the possible role of early vitamin D supplementation in the development of allergy is warranted. Our results also suggest that solar exposure during childhood may be important in allergic sensitization. Plausible explanations, including biologic mechanisms, exist for both observations. © 2010 John Wiley & Sons A/S.",
"title": "The role of latitude, ultraviolet radiation exposure and vitamin D in childhood asthma and hayfever: an Australian multicenter study."
},
{
"docid": "MED-3991",
"text": "Few foods contain ergocalciferol or cholecalciferol. Treatment of mushrooms with UV light increases ergocalciferol content and could provide a dietary source of vitamin D. We evaluated the impact of consuming UV-treated white button mushrooms (Agaricus bisporus) on the vitamin D status of healthy adults. Thirty-eight volunteers were randomized to 4 treatments consumed with a standard meal for 6 wk: the control (C) group received untreated mushrooms providing 0.85 μg/d ergocalciferol (n = 10); groups M1 and M2 received UV-treated mushrooms providing 8.8 (n = 10) and 17.1 μg/d (n = 9), respectively; and the supplement (S) group received purified ergocalciferol plus untreated mushrooms, providing a total of 28.2 μg/d (n = 9). Serum total 25-hydroxyvitamin D [25(OH)D] and 25-hydroxyergocalciferol [25(OH)D2] were 83 ± 38 and 2.4 ± 2.0 nmol/L, respectively, at baseline (mean ± SD). At wk 6, 25(OH)D2 had increased and was higher in all treatment groups than in the C group, whereas 25-hydroxycholecalciferol [25(OH)D3] had decreased and was lower in the M2 and S groups than in the C group. Increases in 25(OH)D2 for groups C, M1, M2, and S were 1.2 ± 5.2, 13.8 ± 7.3, 12.7 ± 3.7, and 32.8 ± 3.3 nmol/L and decreases in 25(OH)D3 were -3.9 ± 16.3, -10.4 ± 6.4, -20.6 ± 14.6, and -29.5 ± 15.9 nmol/L, respectively. Concentrations did not change in group C. In summary, ergocalciferol was absorbed and metabolized to 25(OH)D2 but did not affect vitamin D status, because 25(OH)D3 decreased proportionally.",
"title": "Ergocalciferol from mushrooms or supplements consumed with a standard meal increases 25-hydroxyergocalciferol but decreases 25-hydroxycholecalcifer..."
},
{
"docid": "MED-1578",
"text": "Crohn's disease is a complex inherited disorder of unknown pathogenesis with environmental, genetic and microbial factors involved in the development of the disease. A remarkable feature of this disease in childhood is the effective response to exclusive enteral nutrition (EEN) therapy and the need for complete exclusion of normal diet required for success (principle of exclusivity). EEN or dietary interventions might act through removal of dietary components, which affect microbial composition, decrease a proinflammatory response and promote restitution of the epithelial barrier, likewise allowing termination of this vicious disease-forming cycle before a critical threshold is reached. Multiple traditional and nontraditional dietary components may affect the microbiome, mucous layer, intestinal permeability, or adherence and translocation of pathobionts. We review the epidemiological data, as well as data from animal models and cell lines, and propose a model for pathogenesis we have termed the 'bacterial penetration cycle', whereby dietary components such as animal fat, high sugar intake and gliadin, and consumption of emulsifiers, maltodextrin as well as low-fiber diets may be able to cause a localized acquired bacterial clearance defect, leading to bacterial adhesion and penetration, and subsequently inflammation in the gut. © 2014 S. Karger AG, Basel.",
"title": "Dietary clues to the pathogenesis of Crohn's disease."
},
{
"docid": "MED-5129",
"text": "BACKGROUND: Vitamin B(12) deficiency can occur in individuals with dietary patterns that exclude animal foods and patients who are unable to absorb vitamin B(12 )in food. MATERIAL AND METHOD: Our clinic serves a high-income population living in Southern Israel. We hypothesize that a tendency to decrease of level of vitamin B(12) in our population is caused by a premeditated decrease in consumption of animal products. We analyzed 512 medical histories of patients undergoing blood tests for vitamin B(12) level for various reasons. RESULT: The level of vitamin B(12) in 192 patients (37.5%) was less than 250 pg/ml. CONCLUSION: As a result of media information disseminating the relationship between meat, cholesterol and cardiovascular diseases, consumption of meat, particularly beef, has decreased. Changes in life style among segments of the population with high socioeconomic level, on one hand, and the existence of poverty, on the other, are two main factors in the decreasing consumption of animal products. This causes a decrease in the level of vitamin B(12) in the general population, and as a consequence, this will increase pathology due to vitamin B(12) deficiency. In lieu of these possible developments and in order to prevent serious health problems, vitamin B(12) fortification should be seriously considered and discussed. (c) 2007 S. Karger AG, Basel.",
"title": "Modern society and prospects of low vitamin B12 intake."
},
{
"docid": "MED-2458",
"text": "BACKGROUND: Antioxidant-rich diets are associated with reduced asthma prevalence in epidemiologic studies. We previously showed that short-term manipulation of antioxidant defenses leads to changes in asthma outcomes. OBJECTIVE: The objective was to investigate the effects of a high-antioxidant diet compared with those of a low-antioxidant diet, with or without lycopene supplementation, in asthma. DESIGN: Asthmatic adults (n = 137) were randomly assigned to a high-antioxidant diet (5 servings of vegetables and 2 servings of fruit daily; n = 46) or a low-antioxidant diet (≤2 servings of vegetables and 1 serving of fruit daily; n = 91) for 14 d and then commenced a parallel, randomized, controlled supplementation trial. Subjects who consumed the high-antioxidant diet received placebo. Subjects who consumed the low-antioxidant diet received placebo or tomato extract (45 mg lycopene/d). The intervention continued until week 14 or until an exacerbation occurred. RESULTS: After 14 d, subjects consuming the low-antioxidant diet had a lower percentage predicted forced expiratory volume in 1 s and percentage predicted forced vital capacity than did those consuming the high-antioxidant diet. Subjects in the low-antioxidant diet group had increased plasma C-reactive protein at week 14. At the end of the trial, time to exacerbation was greater in the high-antioxidant than in the low-antioxidant diet group, and the low-antioxidant diet group was 2.26 (95% CI: 1.04, 4.91; P = 0.039) times as likely to exacerbate. Of the subjects in the low-antioxidant diet group, no difference in airway or systemic inflammation or clinical outcomes was observed between the groups that consumed the tomato extract and those who consumed placebo. CONCLUSIONS: Modifying the dietary intake of carotenoids alters clinical asthma outcomes. Improvements were evident only after increased fruit and vegetable intake, which suggests that whole-food interventions are most effective. This trial was registered at http://www.actr.org.au as ACTRN012606000286549.",
"title": "Manipulating antioxidant intake in asthma: a randomized controlled trial."
},
{
"docid": "MED-3461",
"text": "It is well documented in animal and human research that unaccustomed eccentric muscle action of sufficient intensity and/or duration causes disruption of connective and/or contractile tissue. In humans, this appears to be associated with the sensation of delayed onset muscle soreness (DOMS). During the late 1970's, it was proposed that this sensation of soreness might be associated with the acute inflammatory response. However, subsequent research failed to substantiate this theory. The present article suggests that the results of much of the research concerning DOMS reflect events typically seen in acute inflammation. Similarities between the two events include: the cardinal symptoms of pain, swelling, and loss of function; evidence of cellular infiltrates, especially the macrophage; biochemical markers such as increased lysosomal activity and increased circulating levels of some of the acute phase proteins; and histological changes during the initial 72 h. In the final section of this paper, a theoretical sequence of events is proposed, based on research involving acute inflammation and DOMS.",
"title": "Acute inflammation: the underlying mechanism in delayed onset muscle soreness?"
},
{
"docid": "MED-3466",
"text": "This investigation determined the efficacy of a tart cherry juice in aiding recovery and reducing muscle damage, inflammation and oxidative stress. Twenty recreational Marathon runners assigned to either consumed cherry juice or placebo for 5 days before, the day of and for 48 h following a Marathon run. Markers of muscle damage (creatine kinase, lactate dehydrogenase, muscle soreness and isometric strength), inflammation [interleukin-6 (IL-6), C-reactive protein (CRP) and uric acid], total antioxidant status (TAS) and oxidative stress [thiobarbituric acid reactive species (TBARS) and protein carbonyls] were examined before and following the race. Isometric strength recovered significantly faster (P=0.024) in the cherry juice group. No other damage indices were significantly different. Inflammation was reduced in the cherry juice group (IL-6, P<0.001; CRP, P<0.01; uric acid, P<0.05). TAS was ~10% greater in the cherry juice than the placebo group for all post-supplementation measures (P<0.05). Protein carbonyls was not different; however, TBARS was lower in the cherry juice than the placebo at 48 h (P<0.05). The cherry juice appears to provide a viable means to aid recovery following strenuous exercise by increasing total antioxidative capacity, reducing inflammation, lipid peroxidation and so aiding in the recovery of muscle function. © 2009 John Wiley & Sons A/S.",
"title": "Influence of tart cherry juice on indices of recovery following marathon running."
},
{
"docid": "MED-3866",
"text": "Background Obesity leads to an increase in inflammation and insulin resistance. This study determined antioxidant activity of flaxseed and its role in inflammation and insulin resistance in obese glucose intolerant people. Methods Using a randomized crossover design, nine obese glucose intolerant people consumed 40 g ground flaxseed or 40 g wheat bran daily for 12 weeks with a 4-week washout period. Plasma inflammation biomarkers (CRP, TNF-α, and IL-6), glucose, insulin, and thiobaribituric acid reactive substance (TBARS) were measured before and after of each supplementation. Results Flaxseed supplementation decreased TBARS (p = 0.0215) and HOMA-IR (p = 0.0382). Flaxseed or wheat bran supplementation did not change plasma inflammatory biomarkers. A positive relationship was found between TBARS and HOMA-IR (r = 0.62, p = 0.0003). Conclusions The results of the study weakly support that decreased insulin resistance might have been secondary to antioxidant activity of flaxseed. However, the mechanism(s) of decreased insulin resistance by flaxseed should be further determined using flaxseed lignan.",
"title": "Flaxseed supplementation improved insulin resistance in obese glucose intolerant people: a randomized crossover design"
},
{
"docid": "MED-3252",
"text": "It is commonly accepted that nutrition is one of the possible environmental factors involved in the pathogenesis of multiple sclerosis (MS), but its role as complementary MS treatment is unclear and largely disregarded. At present, MS therapy is not associated to a particular diet, probably due to lack of information on the effects of nutrition on the disease. To overcome the distrust of the usefulness of dietary control in MS and to encourage nutritional interventions in the course of the disease, it is necessary to assess the nature and the role of bioactive dietary molecules and their targets, and establish how a dietary control can influence cell metabolism and improve the wellness of MS patients. The aim of this review is to provide a rationale for a nutritional intervention in MS by evaluating at the molecular level the effects of dietary molecules on the inflammatory and autoimmune processes involved in the disease. Present data reveal that healthy dietary molecules have a pleiotropic role and are able to change cell metabolism from anabolism to catabolism and down-regulate inflammation by interacting with enzymes, nuclear receptors and transcriptional factors. The control of gut dysbiosis and the combination of hypo-caloric, low-fat diets with specific vitamins, oligoelements and dietary integrators, including fish oil and polyphenols, may slow-down the progression of the disease and ameliorate the wellness of MS patients. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "The molecular basis of nutritional intervention in multiple sclerosis: a narrative review."
},
{
"docid": "MED-3453",
"text": "There has been no investigation to determine if the widely used over-the-counter, water-soluble antioxidants vitamin C and N-acetyl-cysteine (NAC) could act as pro-oxidants in humans during inflammatory conditions. We induced an acute-phase inflammatory response by an eccentric arm muscle injury. The inflammation was characterized by edema, swelling, pain, and increases in plasma inflammatory indicators, myeloperoxidase and interleukin-6. Immediately following the injury, subjects consumed a placebo or vitamin C (12.5 mg/kg body weight) and NAC (10 mg/kg body weight) for 7 d. The resulting muscle injury caused increased levels of serum bleomycin-detectable iron and the amount of iron was higher in the vitamin C and NAC group. The concentrations of lactate dehydrogenase (LDH), creatine kinase (CK), and myoglobin were significantly elevated 2, 3, and 4 d postinjury and returned to baseline levels by day 7. In addition, LDH and CK activities were elevated to a greater extent in the vitamin C and NAC group. Levels of markers for oxidative stress (lipid hydroperoxides and 8-iso prostaglandin F2alpha; 8-Iso-PGF2alpha) and antioxidant enzyme activities were also elevated post-injury. The subjects receiving vitamin C and NAC had higher levels of lipid hydroperoxides and 8-Iso-PGF2alpha 2 d after the exercise. This acute human inflammatory model strongly suggests that vitamin C and NAC supplementation immediately post-injury, transiently increases tissue damage and oxidative stress.",
"title": "Supplementation with vitamin C and N-acetyl-cysteine increases oxidative stress in humans after an acute muscle injury induced by eccentric exercise."
},
{
"docid": "MED-2762",
"text": "BACKGROUND: Vitamin and mineral supplements are commonly used to prevent chronic diseases. PURPOSE: To systematically review evidence for the benefit and harms of vitamin and mineral supplements in community-dwelling, nutrient-sufficient adults for the primary prevention of cardiovascular disease (CVD) and cancer. DATA SOURCES: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Database of s of Reviews of Effects were searched from January 2005 to 29 January 2013, with manual searches of reference lists and gray literature. STUDY SELECTION: Two investigators independently selected and reviewed fair- and good-quality trials for benefit and fair- and good-quality trials and observational studies for harms. DATA EXTRACTION: Dual quality assessments and data abstraction. DATA SYNTHESIS: Two large trials (n = 27 658) reported lower cancer incidence in men taking a multivitamin for more than 10 years (pooled unadjusted relative risk, 0.93 [95% CI, 0.87 to 0.99]). The study that included women showed no effect in that group. High-quality studies (k = 24; n = 324 653) of single and paired nutrients (such as vitamins A, C, or D; folic acid; selenium; or calcium) were scant and heterogeneous and showed no clear evidence of benefit or harm. Neither vitamin E nor β-carotene prevented CVD or cancer, and β-carotene increased lung cancer risk in smokers. LIMITATIONS: The analysis included only primary prevention studies in adults without known nutritional deficiencies. Studies were conducted in older individuals and included various supplements and doses under the set upper tolerable limits. Duration of most studies was less than 10 years. CONCLUSION: Limited evidence supports any benefit from vitamin and mineral supplementation for the prevention of cancer or CVD. Two trials found a small, borderline-significant benefit from multivitamin supplements on cancer in men only and no effect on CVD. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.",
"title": "Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer: An updated systematic evidence review for the U.S. ..."
},
{
"docid": "MED-3500",
"text": "Multiple studies in animal models have shown that the commonly used food additive carrageenan (CGN) induces inflammation and intestinal neoplasia. We performed the first studies to determine the effects of CGN exposure on human intestinal epithelial cells (IEC) in tissue culture and tested the effect of very low concentrations (1-10 mg/L) of undegraded, high-molecular weight CGN. These concentrations of CGN are less than the anticipated exposure of the human colon to CGN from the average Western diet. In the human colonic epithelial cell line NCM460 and in primary human colonic epithelial cells that were exposed to CGN for 1-8 d, we found increased cell death, reduced cell proliferation, and cell cycle arrest compared with unexposed control cells. After 6-8 d of CGN exposure, the percentage of cells reentering G0-G1 significantly decreased and the percentages of cells in S and G2-M phases significantly increased. Increases in activated p53, p21, and p15 followed CGN exposure, consistent with CGN-induced cell cycle arrest. Additional data, including DNA ladder, poly ADP ribose polymerase Western blot, nuclear DNA staining, and activities of caspases 3 and 7, indicated no evidence of increased apoptosis following CGN exposure and were consistent with CGN-induced necrotic cell death. These data document for the first time, to our knowledge, marked adverse effects of low concentrations of CGN on survival of normal human IEC and suggest that CGN exposure may have a role in development of human intestinal pathology.",
"title": "Carrageenan induces cell cycle arrest in human intestinal epithelial cells in vitro."
},
{
"docid": "MED-837",
"text": "OBJECTIVE: We performed this study as a pilot experiment to investigate the short term effects of two diets of varying composition on weight loss as the primary outcome in obese women with polycystic ovary syndrome (PCOS) seeking fertility. DESIGN: Randomized clinical trial. SETTING: Academic medical center. PATIENT(S): Thirty-five obese women with PCOS. INTERVENTION(S): We examined the effects of a 1-month dietary intervention on the PCOS phenotype. Participants were randomized to one of two energy-restricted diets; high protein (HP: 30% protein, 40% carbohydrate, and 30% fat) or high carbohydrate (HC: 15% protein, 55% carbohydrate, and 30% fat). The fat content was held constant in both diets. MAIN OUTCOME MEASURE(S): Primary - change in body weight; Secondary - biometric, hormonal, lipid and lipoprotein, and markers of glucose homeostasis and energy metabolism. RESULT(S): Twenty-six women completed the study. Both the HP (-3.7 +/- 1.9 kg) and HC (-4.4 +/- 1.5 kg) diets resulted in significant weight loss, but there was no significant difference in mean weight loss between the two groups. There were also no differences between diets on a variety of measures including circulating androgens, measures of glucose metabolism, and leptin. However, the effects of a hypocaloric diet per se on improving metabolic and reproductive abnormalities in a group of PCOS women were marked by a decline in circulating androgens (P=.03), fasting and area under the curve (AUC) insulins (P<.05) on a 3-hour oral glucose tolerance test (OGTT), and fasting and AUC leptin levels (P<.0001). There was a high prevalence of menstrual bleeding during the trial (14 out of 26 patients). CONCLUSION(S): Those who completed the short-term hypocaloric diet had a significant weight loss and a significant improvement in their reproductive and metabolic abnormalities. There was no increased benefit to a high-protein diet. Future diet studies evaluating the ideal composition of a hypocaloric diet in women with PCOS will require a large study population, and will most likely require a multicenter trial.",
"title": "A randomized trial of the effects of two types of short-term hypocaloric diets on weight loss in women with polycystic ovary syndrome."
},
{
"docid": "MED-855",
"text": "Hydrogen peroxide is an oxidising agent that is used in a number of household products, including general-purpose disinfectants, chlorine-free bleaches, fabric stain removers, contact lens disinfectants and hair dyes, and it is a component of some tooth whitening products. In industry, the principal use of hydrogen peroxide is as a bleaching agent in the manufacture of paper and pulp. Hydrogen peroxide has been employed medicinally for wound irrigation and for the sterilisation of ophthalmic and endoscopic instruments. Hydrogen peroxide causes toxicity via three main mechanisms: corrosive damage, oxygen gas formation and lipid peroxidation. Concentrated hydrogen peroxide is caustic and exposure may result in local tissue damage. Ingestion of concentrated (>35%) hydrogen peroxide can also result in the generation of substantial volumes of oxygen. Where the amount of oxygen evolved exceeds its maximum solubility in blood, venous or arterial gas embolism may occur. The mechanism of CNS damage is thought to be arterial gas embolisation with subsequent brain infarction. Rapid generation of oxygen in closed body cavities can also cause mechanical distension and there is potential for the rupture of the hollow viscus secondary to oxygen liberation. In addition, intravascular foaming following absorption can seriously impede right ventricular output and produce complete loss of cardiac output. Hydrogen peroxide can also exert a direct cytotoxic effect via lipid peroxidation. Ingestion of hydrogen peroxide may cause irritation of the gastrointestinal tract with nausea, vomiting, haematemesis and foaming at the mouth; the foam may obstruct the respiratory tract or result in pulmonary aspiration. Painful gastric distension and belching may be caused by the liberation of large volumes of oxygen in the stomach. Blistering of the mucosae and oropharyngeal burns are common following ingestion of concentrated solutions, and laryngospasm and haemorrhagic gastritis have been reported. Sinus tachycardia, lethargy, confusion, coma, convulsions, stridor, sub-epiglottic narrowing, apnoea, cyanosis and cardiorespiratory arrest may ensue within minutes of ingestion. Oxygen gas embolism may produce multiple cerebral infarctions. Although most inhalational exposures cause little more than coughing and transient dyspnoea, inhalation of highly concentrated solutions of hydrogen peroxide can cause severe irritation and inflammation of mucous membranes, with coughing and dyspnoea. Shock, coma and convulsions may ensue and pulmonary oedema may occur up to 24-72 hours post exposure. Severe toxicity has resulted from the use of hydrogen peroxide solutions to irrigate wounds within closed body cavities or under pressure as oxygen gas embolism has resulted. Inflammation, blistering and severe skin damage may follow dermal contact. Ocular exposure to 3% solutions may cause immediate stinging, irritation, lacrimation and blurred vision, but severe injury is unlikely. Exposure to more concentrated hydrogen peroxide solutions (>10%) may result in ulceration or perforation of the cornea. Gut decontamination is not indicated following ingestion, due to the rapid decomposition of hydrogen peroxide by catalase to oxygen and water. If gastric distension is painful, a gastric tube should be passed to release gas. Early aggressive airway management is critical in patients who have ingested concentrated hydrogen peroxide, as respiratory failure and arrest appear to be the proximate cause of death. Endoscopy should be considered if there is persistent vomiting, haematemesis, significant oral burns, severe abdominal pain, dysphagia or stridor. Corticosteroids in high dosage have been recommended if laryngeal and pulmonary oedema supervene, but their value is unproven. Endotracheal intubation, or rarely, tracheostomy may be required for life-threatening laryngeal oedema. Contaminated skin should be washed with copious amounts of water. Skin lesions should be treated as thermal burns; surgery may be required for deep burns. In the case of eye exposure, the affected eye(s) shod eye(s) should be irrigated immediately and thoroughly with water or 0.9% saline for at least 10-15 minutes. Instillation of a local anaesthetic may reduce discomfort and assist more thorough decontamination.",
"title": "Hydrogen peroxide poisoning."
},
{
"docid": "MED-4683",
"text": "Background/Objectives Vegans and to a lesser extent vegetarians have low average circulating concentrations of vitamin B12; however, the relation between factors such as age or time on these diets and vitamin B12 concentrations is not clear. The objectives were to investigate differences in serum vitamin B12 and folate concentrations between omnivores, vegetarians and vegans and to ascertain whether vitamin B12 concentrations differed by age and time on the diet. Subjects/Methods A cross-sectional analysis involving 689 men (226 omnivores, 231 vegetarians and 232 vegans) from the European Prospective Investigation into Cancer and Nutrition Oxford cohort. Results Mean serum vitamin B12 was highest among omnivores (281, 95% CI: 270-292 pmol/l), intermediate in vegetarians (182, 95% CI: 175-189 pmol/l), and lowest in vegans (122, 95% CI: 117-127 pmol/l). Fifty-two percent of vegans, 7% of vegetarians and one omnivore were classified as vitamin B12 deficient (defined as serum vitamin B12 < 118 pmol/l). There was no significant association between age or duration of adherence to a vegetarian or a vegan diet and serum vitamin B12. In contrast, folate concentrations were highest among vegans, intermediate in vegetarians, and lowest in omnivores, but only two men (both omnivores) were categorised as folate deficient (defined as serum folate < 6.3 nmol/l). Conclusion Vegans have lower vitamin B12 concentrations, but higher folate concentrations, than vegetarians and omnivores. Half of the vegans were categorised as vitamin B12 deficient and would be expected to have a higher risk of developing clinical symptoms related to vitamin B12 deficiency.",
"title": "Serum concentrations of vitamin B12 and folate in British male omnivores, vegetarians, and vegans: results from a cross-sectional analysis of the EPIC-Oxford cohort study"
},
{
"docid": "MED-922",
"text": "INTRODUCTION: Vegetarian diets are considered to promote health and reduce the risk of some chronic diseases. It is also known that restriction or exclusion of animal foods may result in low intake of essential nutrients. The aim of the presented study was to assess the intake and serum status of vitamin B12, folate, vitamins A, E and D, as well as concentrations of homocysteine, total antioxidant status and iron balance in Polish vegetarian children. MATERIAL AND METHODS: The study included 50 children, aged 5-11 who had been referred to the Institute of Mother and Child for dietary consultation. From those, 32 were vegetarians (aged 6.5±4.2 years) and 18 omnivores (aged 7.9±2.7 years). Dietary constituents were analyzed using the nutritional programme Dietetyk2®. Folate and vitamin B12 were determined with a chemiluminescence immunoassay, total homocysteine with a fluorescence polarization immunoassay and TAS (total antioxidant status) by colorimetric method. Vitamin A and E in serum were determined by the high-pressure liquid chromatography method (HPLC) and vitamin D by immunoenzymatic assay (ELISA). Concentrations of iron, ferritin, transferrin and total iron-binding capacity (TIBC) in serum were determined by commercially available kits. RESULTS: In vegetarian children daily intake of vitamin B12 (1.6 ěg) was in the recommended range, that of folate (195 ěg) and vitamin A (1245 ěg) higher, but vitamin E slightly lower (6.6 ěg) and three-fold lower vitamin D (1.1 ěg) than references allowance. Serum concentrations of vitamin B12 (548 pg/ml), folate (12.8 ng/ml), vitamin A (1.2 ěmol/L), vitamin E (15.6 ěmol/l) were within physiological range, but that of vitamin D (13.7 ěg/L) was only half of the lowest limit of the reference value. In vegetarian children in comparison to omnivorous similar levels of homocysteine (6.13 ěmol/L vs 5.45 ěmol/L) and vitamin A (1,17 ěmol/L vs 1.32 ěmol/L) were observed. Lower (p<0.05) values of vitamin E (15.6 ěmol/L vs 18.4 ěmol/L) and TAS (1.21 mmol/L vs 1.30 mmol/L; p<0.0001) were found. Concentrations of iron markers were in physiological range. CONCLUSION: Obtained results indicated that intakes of vitamin B12 and folic acid from vegetarian diets are sufficient to maintain serum concentrations of both homocysteine and iron in the range observed in omnivorous children. High consumption of vitamin A and low vitamin E only slightly affected their serum values. Significantly lower concentration of serum vitamin E in vegetarian children in comparison to nonvegetarians may be reflected with statistically significant lowering of total antioxidant status. Insufficient intake of vitamin D and its low serum concentration should be under close monitoring in vegetarian children. In order to prevent vitamin D deficiency appropriate age-dependent supplementation should be considered.",
"title": "The effect of vegetarian diet on selected essential nutrients in children."
},
{
"docid": "MED-3798",
"text": "The Moos Menstrual Distress Questionnaire (MMDQ) was completed by thirty healthy premenopausal women randomized into one of two sets of weight-maintaining diets, those with a ratio of polyunsaturated to saturated fatty acids (P/S ratio) of 1.0 and those with a P/S ratio of 0.3. After a baseline interval of one menstrual cycle, both groups were fed a high fat diet (40% energy from fat) for four menstrual cycles per subject, followed by a similar interval on a low fat diet (20% energy from fat). There were no significant differences in self-reported menstrual symptoms between the two P/S groups. During both menses and the premenstrual week of the low fat dietary period there were significant decreases in self-reported symptoms associated with water retention. A decrease in symptoms in the group labelled \"arousal\" during the rest of the menstrual cycle was also reported.",
"title": "Influence of dietary fat on self-reported menstrual symptoms."
},
{
"docid": "MED-2670",
"text": "As the population of people in the United States over the age of 65 years continues to increase, so too will the incidence of age-related pathologies, including decreases in cognitive and motor function. In cases of severe deficits in memory or motor function, hospitalization and/or custodial care would be a likely outcome. This means that unless some way is found to reduce these age-related decrements in neuronal function, health care costs will continue to rise exponentially. Evidence is accumulating that consumption of blueberries may be one strategy to forestall or even reverse age-related neuronal deficits, as well as their subsequent behavioral manifestations, in order to increase healthy aging. Research suggests that the polyphenolic compounds found in blueberries exert their beneficial effects either through their ability to lower oxidative stress and inflammation or directly by altering the signaling involved in neuronal communication. These interventions, in turn, may protect against age-related deficits in cognitive and motor function. Appropriately, the US Department of Agriculture has figured prominently in these discoveries, through the efforts of two USDA researchers who worked for the department 100 years apart. Copyright © 2012 S. Karger AG, Basel.",
"title": "Blueberries and neuronal aging."
},
{
"docid": "MED-4844",
"text": "Rheumatoid arthritis (RA) is characterized by inflammation of the synovial tissues in the joints. A number of papers related to dietary components that are associated with this inflammation are reviewed. In addition, the ecological approach is used to study the links between diet and RA. Multi-country data for prevalence of RA for females from eight and fifteen countries were compared statistically with components of national dietary supply. Fat from meat and offal for the period 2 years before the prevalence data was found to have the highest statistical association with the prevalence of RA (r(2) 0.877, P<0.001 for eight countries). The statistical correlations for meat and offal were almost as high as those for their fat. Similar correlations were found for temporal changes in indices of effects of RA in several European countries between 1968 and 1978 as more meat was added to the national diets, although the correlations were higher for meat than for fat. It is hypothesized that meat and offal may be a major factor contributing to the inflammation in RA. In the present short review, the author examines some of the data that associate meat consumption with RA and the possible factors, e.g. fat, Fe and nitrite, which may contribute to the inflammation.",
"title": "The role of meat in the expression of rheumatoid arthritis."
},
{
"docid": "MED-4710",
"text": "OBJECTIVE: Recent studies have suggested that nuts have favorable effects beyond lipid lowering. We aimed to investigate effect of the Antep pistachio (Pistacia vera L.) on blood glucose, lipid parameters, endothelial function, inflammation, and oxidation in healthy young men living in a controlled environment. METHODS: A Mediterranean diet was administered to normolipidemic 32 healthy young men (mean age 22 y, range 21-24) for 4 wk. After 4 wk, participants continued to receive the Mediterranean diet but pistachio was added for 4 wk by replacing the monounsaturated fat content constituting approximately 20% of daily caloric intake. Fasting blood samples and brachial endothelial function measurements were performed at baseline and after each diet. RESULTS: Compared with the Mediterranean diet, the pistachio diet decreased glucose (P<0.001, -8.8+/-8.5%), low-density lipoprotein (P<0.001, -23.2+/-11.9%), total cholesterol (P<0.001, -21.2+/-9.9%), and triacylglycerol (P=0.008, -13.8+/-33.8%) significantly and high-density lipoprotein (P=0.069, -3.1+/-11.7%) non-significantly. Total cholesterol/high-density lipoprotein and low-density lipoprotein/high-density lipoprotein ratios decreased significantly (P<0.001 for both). The pistachio diet significantly improved endothelium-dependent vasodilation (P=0.002, 30% relative increase), decreased serum interleukin-6, total oxidant status, lipid hydroperoxide, and malondialdehyde and increased superoxide dismutase (P<0.001 for all), whereas there was no significant change in C-reactive protein and tumor necrosis factor-alpha levels. CONCLUSION: In this trial, we demonstrated that a pistachio diet improved blood glucose level, endothelial function, and some indices of inflammation and oxidative status in healthy young men. These findings are in accordance with the idea that nuts, in particular pistachio nuts, have favorable effects beyond lipid lowering that deserve to be evaluated with prospective follow-up studies. Copyright 2010. Published by Elsevier Inc.",
"title": "Effect of pistachio diet on lipid parameters, endothelial function, inflammation, and oxidative status: a prospective study."
},
{
"docid": "MED-1386",
"text": "Inflammation is one mechanism through which cancer is initiated and progresses, and is implicated in the etiology of other conditions that affect cancer risk and prognosis, such as type 2 diabetes, cardiovascular disease, and visceral obesity. Emerging human evidence, primarily epidemiological, suggests that walnuts impact risk of these chronic diseases via inflammation. The published literature documents associations between walnut consumption and reduced risk of cancer, and mortality from cancer, diabetes, and cardiovascular disease, particularly within the context of the Mediterranean Diet. While encouraging, follow-up in human intervention trials is needed to better elucidate any potential cancer prevention effect of walnuts, per se. In humans, the far-reaching positive effects of a plant-based diet that includes walnuts may be the most critical message for the public. Indeed, appropriate translation of nutrition research is essential for facilitating healthful consumer dietary behavior. This paper will explore the translation and application of human evidence regarding connections with cancer and biomarkers of inflammation to the development of dietary guidance for the public and individualized dietary advice. Strategies for encouraging dietary patterns that may reduce cancer risk will be explored.",
"title": "Communicating clinical research to reduce cancer risk through diet: Walnuts as a case example"
},
{
"docid": "MED-2942",
"text": "BACKGROUND: There are no long-term prospective studies assessing the impact of the vegan diet on vitamin B-12 (B-12) status. Many vegans take B-12 supplements irregularly or refuse to adopt them at all, considering them to be \"unnatural\" products. The use of B-12 fortified food may be an alternative. Therefore, we aimed to estimate the long-term effect of a vegan diet on serum B-12 concentrations in healthy omnivore adults, comparing the influence of natural products consumption and B-12 fortified food. MATERIAL AND METHODS: A five year prospective study was carried out comprising 20 omnivore healthy adult subjects, who moved to strict vegan diet for 5 years. Ten volunteers followed vegan diet based entirely on natural products, while the remaining ten subjects consumed food fortified in B-12. In all subjects serum vitamin B-12 concentration was determined before and 6, 12, 24 and 60 months after the implementation of the diet. RESULTS: A significant decrease (p < 0.0002) of serum B-12 concentrations in the whole studied group was noted after 60 months of vegan diet. However, observed changes were in fact limited to the subgroup consuming exclusively natural products (p < 0.0001). CONCLUSIONS: Transition from omnivore to vegan diet is associated with the risk of vitamin B-12 deficiency. B-12 fortified products might constitute a valuable alternative in vegans refusing to take vitamin supplements.",
"title": "The impact of vegan diet on B-12 status in healthy omnivores: five-year prospective study."
},
{
"docid": "MED-4627",
"text": "The emerging role of chronic inflammation in the major degenerative diseases of modern society has stimulated research into the influence of nutrition and dietary patterns on inflammatory indices. Most human studies have correlated analyses of habitual dietary intake as determined by a food frequency questionnaire or 24-hour recall with systemic markers of inflammation like high-sensitivity C-reactive protein (HS-CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). An occasional study also includes nutrition analysis of blood components. There have been several controlled interventions which evaluated the effect of a change in dietary pattern or of single foods on inflammatory markers in defined populations. Most studies reveal a modest effect of dietary composition on some inflammatory markers in free-living adults, although different markers do not vary in unison. Significant dietary influences have been established for glycemic index (GI) and load (GL), fiber, fatty acid composition, magnesium, carotenoids, and flavonoids. A traditional Mediterranean dietary pattern, which typically has a high ratio of monounsaturated (MUFA) to saturated (SFA) fats and ω-3 to ω-6 polyunsaturated fatty acid (PUFAs) and supplies an abundance of fruits, vegetables, legumes, and grains, has shown anti-inflammatory effects when compared with typical North American and Northern European dietary patterns in most observational and interventional studies and may become the diet of choice for diminishing chronic inflammation in clinical practice.",
"title": "Diet and inflammation."
},
{
"docid": "MED-4278",
"text": "OBJECTIVE: To describe the lifestyle characteristics and nutrient intakes of the Oxford cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC). DESIGN: Cohort of men and women recruited through general practices or by post to include a high proportion of non meat-eaters. Dietary, anthropometric and lifestyle data were collected at baseline and four diet groups were defined. SETTING: United Kingdom. PARTICIPANTS: In total, 65 429 men and women aged 20 to 97 years, comprising 33 883 meat-eaters, 10 110 fish-eaters, 18 840 lacto-ovo vegetarians and 2596 vegans. RESULTS: Nutrient intakes and lifestyle factors differed across the diet groups, with striking differences between meat-eaters and vegans, and fish-eaters and vegetarians usually having intermediate values. Mean fat intake in each diet group was below the UK dietary reference value of 33% of total energy intake. The mean intake of saturated fatty acids in vegans was approximately 5% of energy, less than half the mean intake among meat-eaters (10-11%). Vegans had the highest intakes of fibre, vitamin B1, folate, vitamin C, vitamin E, magnesium and iron, and the lowest intakes of retinol, vitamin B12, vitamin D, calcium and zinc. CONCLUSIONS: The EPIC-Oxford cohort includes 31 546 non meat-eaters and is one of the largest studies of vegetarians in the world. The average nutrient intakes in the whole cohort are close to those currently recommended for good health. Comparisons of the diet groups show wide ranges in the intakes of major nutrients such as saturated fat and dietary fibre. Such variation should increase the ability of the study to detect associations of diet with major cancers and causes of death.",
"title": "EPIC-Oxford: lifestyle characteristics and nutrient intakes in a cohort of 33 883 meat-eaters and 31 546 non meat-eaters in the UK."
},
{
"docid": "MED-4104",
"text": "BACKGROUND: Although vegan diets improve diabetes management, little is known about the nutrient profiles or diet quality of individuals with type 2 diabetes who adopt a vegan diet. OBJECTIVE: To assess the changes in nutrient intake and dietary quality among participants following a low-fat vegan diet or the 2003 American Diabetes Association dietary recommendations. DESIGN: A 22-week randomized, controlled clinical trial examining changes in nutrient intake and diet quality. SUBJECTS/SETTING: Participants with type 2 diabetes (n=99) in a free-living setting. RESEARCH DESIGN AND METHODS: Participants were randomly assigned to a low-fat vegan diet or a 2003 American Diabetes Association recommended diet. MAIN OUTCOME MEASURES: Nutrient intake and Alternate Healthy Eating Index (AHEI) scores were collected at baseline and 22 weeks. STATISTICAL ANALYSES PERFORMED: Between-group t tests were calculated for changes between groups and paired comparison t tests were calculated for changes within-group. Pearson's correlation assessed relationship of AHEI score to hemoglobin A1c and body weight changes. RESULTS: Both groups reported significant decreases in energy, protein, fat, cholesterol, vitamin D, selenium, and sodium intakes. The vegan group also significantly reduced reported intakes of vitamin B-12 and calcium, and significantly increased carbohydrate, fiber, total vitamin A activity, beta carotene, vitamins K and C, folate, magnesium, and potassium. The American Diabetes Association recommended diet group also reported significant decreases in carbohydrate and iron, but reported no significant increases. The vegan group significantly improved its AHEI score (P<0.0001), while the American Diabetes Association recommended diet group did not (P=0.7218). The difference in AHEI score at 22 weeks between groups was significant (P<0.0001). With both groups combined, AHEI score was negatively correlated with both changes in hemoglobin A1c value (r=-0.24, P=0.016) and weight (r=-0.27, P=0.007). CONCLUSIONS: Vegan diets increase intakes of carbohydrate, fiber, and several micronutrients, in contrast with the American Diabetes Association recommended diet. The vegan group improved its AHEI score whereas the American Diabetes Association recommended diet group's AHEI score remained unchanged.",
"title": "Changes in nutrient intake and dietary quality among participants with type 2 diabetes following a low-fat vegan diet or a conventional diabetes di..."
}
] |
7049
|
Why do shareholders participate in shorting stocks?
|
[
{
"docid": "348445",
"text": "In short (pun intended), the shareholder lending the shares does not believe that the shares will fall, even though the potential investor does. The shareholder believes that the shares will rise. Because the two individuals believe that a different outcome will occur, they are able to make a trade. By using the available data in the market, they have arrived at a particular conclusion of the fair price for the trade, but each individual wants to be on the other side of it. Consider a simpler form of your question: Why would a shareholder agree to sell his/her shares? Why don't they just wait to sell, when the price is higher? After all, that is why the buyer wants to purchase the shares. On review, I realize I've only stated here why the original shareholder wouldn't simply sell and rebuy the share themselves (because they have a different view of the market). As to why they would actually allow the trade to occur - Zak (and other answers) point out that the shares being lent are compensated for by an initial fee on the transaction + the chance for interest during the period that the shares are owed for.",
"title": ""
},
{
"docid": "247313",
"text": "\"There are two primary reasons shares are sold short: (1) to speculate that a stock's price will decline and (2) to hedge some other related financial exposure. The first is acknowledged by the question. The second reason may be done for taxes (shorting \"\"against the box\"\" was once permitted for tax purposes), for arbitrage positions such as merger arbitrage and situations when an outright sale of stock is not permitted, such as owning restricted stock such as employer-granted shares. Why would a shareholder lend the investor the shares? The investor loaning his stock out to short-sellers earns interest on those shares that the borrower pays. It is not unusual for the annualized cost of borrowing stock to be double digits when there is high demand for heavily shorted shares. This benefit is however not available to all investors.\"",
"title": ""
},
{
"docid": "181673",
"text": "Why would a shareholder lend the investor the shares? Some brokers like IB will pay you to lend your shares: http://ibkb.interactivebrokers.com/node/1838 If you buy shares on margin, you don't have much of a choice. Your broker is allowed to lend your shares to short-sellers.",
"title": ""
},
{
"docid": "434224",
"text": "\"When I have stock at my brokerage account, the title is in street name - the brokerage's name and the quantity I own is on the books of the brokerage (insured by SIPC, etc). The brokerage loans \"\"my\"\" shares to a short seller and is happy to facilitate trades in both directions for commissions (it's a nice trick to get other parties to hold the inventory while you reap income from the churn); by selecting the account I have I don't get to choose to not loan out the shares.\"",
"title": ""
},
{
"docid": "461062",
"text": "\"For the same reason that people bet on different teams. Some think the Tigers will win, others thing the Yankees will win. They wager $5 on it. One of them wins, the other loses. In a short, one person bets that the stock goes down, the other bets that the stock goes up (or hold). You're basically saying \"\"I think this stock is going to hold it's value or go up. If I thought it would go down, like you do, I would sell it myself right now. Instead, I'll let you have it for a while because when I get it back I think I'll come out on top.\"\"\"",
"title": ""
},
{
"docid": "511280",
"text": "One thing no one else has touched on is the issue of time frame. If I'm looking to hold my shares over the next few years, I don't mind riding out a few short-term bumps, while the short-seller is looking to make a quick profit on some bad news. Sure, I could sell and rebuy, but that's a lot of hassle, not to mention commissions and tax issues.",
"title": ""
},
{
"docid": "13240",
"text": "Because they receive compensation (generally interest + dividends) for loaning out the shares. I own an asset X. Somebody else wants to borrow asset X for some time period. I agree to loan them asset X in return for some form of compensation (generally a rate of interest plus, in this specific case, any dividend payments). The reasons why I own asset X, and why they want to borrow asset X are irrelevant to the transaction. The only relevant points are the amount of compensation and the risk that they might default on the loan. This applies equally well to shares as to money or any other kind of loan-able asset.",
"title": ""
},
{
"docid": "255978",
"text": "Short sellers have to pay interest on the borrowings to the shareholders. Although many times brokers don't pass on these earnings to the shareholders, this is the exchange.",
"title": ""
}
] |
[
{
"docid": "202960",
"text": "No. You shorted the stock so you are not a shareholder. If you covered your short, again you are not a shareholder as you statement of account must show. You cannot participate in the net settlement fund.",
"title": ""
},
{
"docid": "86040",
"text": "\"Unrealistic assumption, but I'll play along. Ultimately, dividends would exist because some innovative shareholder of some company, at some time, would desire income from their investment and could propose the idea of sharing the profit. Like-minded investors also desiring income could vote for dividends to come into existence — or, rather, vote for a board of directors that supports enactment of the idea. (In your fictitious world, shareholders do still control the corporation, right?) In this world, though, dividends wouldn't be called \"\"dividends\"\", a terrible name that's too \"\"mathy\"\" for the inhabitants of that world. Rather, they would institute a quarterly or annual shareholder profit share. Governments would enact legislation to approve of—nay, encourage such an innovation because it becomes a new source of recurring income they can tax. Alternatively, even if the idea of a cash dividend didn't occur to anybody in that world, investors would realize the stock price is depressed and could propose and vote for the board to institute share buybacks. The company repurchasing some portion of shares periodically would provide income to shareholders participating in the buyback. If the buyback were oversubscribed, they could structure it fairly (pro-rata participation, etc.) Alternatively, shareholders would pressure the board (or fire them and vote in a new board) to put the company up for sale and find a larger buyer, who would purchase the shares for cash. This can't scale forever, though, so the pressure will increase for solutions like #1 and #2.\"",
"title": ""
},
{
"docid": "534870",
"text": "Why do companies exist? Well, the corporate charter describes why the company exists. Usually the purpose is to enrich the shareholders. The owners of a company want to make money, in other words. There are a number of ways that a shareholder can make money off a stock: As such, maintaining the stock price and dividend payouts are generally the number one concern for any company in the long term. Most of the company's business is going to be directed towards making the company more valuable for a future buyout, or more valuable in terms of what it can pay its shareholders directly. Note that the company doesn't always need to be worried about the specifics of the day-to-day moves of the stock. If it keeps the finances in line - solid profits, margins, earnings growth and the like - and can credibly tell people that it's generally a valuable business, it can usually shrug off any medium-term blips as market craziness. Some companies are more explicitly long-term about things than others (e.g. Berkshire Hathaway basically tells people that it doesn't care all that much about what happens in the short term). Of course, companies are abstractions, and they're run by people. To make the people running the company worry about the stock price, you give them stock. Or stock options, or something like that. A major executive at a big company is likely to have a significant amount of stock. If the company does well, he does well; if it does poorly, he does poorly. Despite a few limitations, this is really a powerful incentive. If a company is losing a lot of money, or if its profits are falling so it's just losing a lot of its value as a business, the owners (stockholders) tend to get upset, and may vote in new management, or launch some sort of shareholder lawsuit. And, as previously noted, to raise funds, a company can also issue new shares to the market as a secondary offering as well (and they can issue fewer shares if the price is high - meaning that whatever the company is worth afterward, the existing owners own proportionally more of it).",
"title": ""
},
{
"docid": "517323",
"text": "The stock market is just like any other market, but stocks are bought and sold here. Just like you buy and sell your electronics at the electronics market, this is a place where buyers and sellers come together to buy and sell shares or stocks or equity, no matter what you call it. What are these shares? A share is nothing but a portion of ownership of a company. Suppose a company has 100 shares issued to it, and you were sold 10 out of those, it literally means you are a 10% owner of the company. Why do companies sell shares? Companies sell shares to grow or expand. Suppose a business is manufacturing or producing and selling goods or services that are high in demand, the owners would want to take advantage of it and increase the production of his goods or services. And in order to increase production he would need money to buy land or equipment or labor, etc. Now either he could go get a loan by pledging something, or he could partner with someone who could give him money in exchange for some portion of the ownership of the company. This way, the owner gets the money to expand his business and make more profit, and the lender gets a portion of profit every time the company makes some. Now if the owner decides to sell shares rather than getting a loan, that's when the stock market comes into the picture. Why would a person want to trade stocks? First of all, please remember that stocks were never meant to be traded. You always invest in stocks. What's the difference? Trading is short term and investing is long term, in very simple language. It's the greed of humans which led to this concept of trading stocks. A person should only buy stocks if he believes in the business the company is doing and sees the potential of growth. Back to the question: a person would want to buy stocks of the company because: How does a stock market help society? Look around you for the answer to this question. Let me give you a start and I wish everyone reading this post to add at least one point to the answer. Corporations in general allow many people come together and invest in a business without fear that their investment will cause them undue liability - because shareholders are ultimately not liable for the actions of a corporation. The cornerstone North American case of how corporations add value is by allowing many investors to have put money towards the railroads that were built across America and Canada. For The stock market in particular, by making it easier to trade shares of a company once the company sells them, the number of people able to conveniently invest grows exponentially. This means that someone can buy shares in a company without needing to knock door to door in 5 years trying to find someone to sell to. Participating in the stock market creates 'liquidity', which is essentially the ease with which stocks are converted into cash. High liquidity reduces risk overall, and it means that those who want risk [because high risk often creates high reward] can buy shares, and those who want low risk [because say they are retiring and don't have a risk appetite anymore] can sell shares.",
"title": ""
},
{
"docid": "569565",
"text": "\"I thought the other answers had some good aspect but also some things that might not be completely correct, so I'll take a shot. As noted by others, there are three different types of entities in your question: The ETF SPY, the index SPX, and options contracts. First, let's deal with the options contracts. You can buy options on the ETF SPY or marked to the index SPX. Either way, options are about the price of the ETF / index at some future date, so the local min and max of the \"\"underlying\"\" symbol generally will not coincide with the min and max of the options. Of course, the closer the expiration date on the option, the more closely the option price tracks its underlying directly. Beyond the difference in how they are priced, the options market has different liquidity, and so it may not be able to track quick moves in the underlying. (Although there's a reasonably robust market for option on SPY and SPX specifically.) Second, let's ask what forces really make SPY and SPX move together as much as they do. It's one thing to say \"\"SPY is tied to SPX,\"\" but how? There are several answers to this, but I'll argue that the most important factor is that there's a notion of \"\"authorized participants\"\" who are players in the market who can \"\"create\"\" shares of SPY at will. They do this by accumulating stock in the constituent companies and turning them into the market maker. There's also the corresponding notion of \"\"redemption\"\" by which an authorized participant will turn in a share of SPY to get stock in the constituent companies. (See http://www.spdrsmobile.com/content/how-etfs-are-created-and-redeemed and http://www.etf.com/etf-education-center/7540-what-is-the-etf-creationredemption-mechanism.html) Meanwhile, SPX is just computed from the prices of the constituent companies, so it's got no market forces directly on it. It just reflects what the prices of the companies in the index are doing. (Of course those companies are subject to market forces.) Key point: Creation / redemption is the real driver for keeping the price aligned. If it gets too far out of line, then it creates an arbitrage opportunity for an authorized participant. If the price of SPY gets \"\"too high\"\" compared to SPX (and therefore the constituent stocks), an authorized participant can simultaneously sell short SPY shares and buy the constituent companies' stocks. They can then use the redemption process to close their position at no risk. And vice versa if SPY gets \"\"too low.\"\" Now that we understand why they move together, why don't they move together perfectly. To some extent information about fees, slight differences in composition between SPY and SPX over time, etc. do play. The bigger reasons are probably that (a) there are not a lot of authorized participants, (b) there are a relatively large number of companies represented in SPY, so there's some actual cost and risk involved in trying to quickly buy/sell the full set to capture the theoretical arbitrage that I described, and (c) redemption / creation units only come in pretty big blocks, which complicates the issues under point b. You asked about dividends, so let me comment briefly on that too. The dividend on SPY is (more or less) passing on the dividends from the constituent companies. (I think - not completely sure - that the market maker deducts its fees from this cash, so it's not a direct pass through.) But each company pays on its own schedule and SPY does not make a payment every time, so it's holding a corresponding amount of cash between its dividend payments. This is factored into the price through the creation / redemption process. I don't know how big of a factor it is though.\"",
"title": ""
},
{
"docid": "209754",
"text": "\"The value of a stock ultimately is related to the valuation of a corporation. As part of the valuation, you can estimate the cash flows (discounted to present time) of the expected cash flows from owning a share. This stock value is the so-called \"\"fundamental\"\" value of a stock. What you are really asking is, how is the stock's market price and the fundamental value related? And by asking this, you have implicitly assumed they are not the same. The reason that the fundamental value and market price can diverge is that simply, most shareholders will not continue holding the stock for the lifespan of a company (indeed some companies have been around for centuries). This means that without dividends or buybacks or liquidations or mergers/acquisitions, a typical shareholder cannot reasonably expect to recoup their share of the company's equity. In this case, the chief price driver is the aggregate expectation of buyers and sellers in the marketplace, not fundamental evaluation of the company's balance sheet. Now obviously some expectations are based on fundamentals and expert opinions can differ, but even when all the experts agree roughly on the numbers, it may be that the market price is quite a ways away from their estimates. An interesting example is given in this survey of behavioral finance. It concerns Palm, a wholly-owned subsidiary of 3Com. When Palm went public, its shares went for such a high price, they were significantly higher than 3Com's shares. This mispricing persisted for several weeks. Note that this facet of pricing is often given short shrift in standard explanations of the stock market. It seems despite decades of academic research (and Nobel prizes being handed out to behavioral economists), the knowledge has been slow to trickle down to laymen, although any observant person will realize something is amiss with the standard explanations. For example, before 2012, the last time Apple paid out dividends was 1995. Are we really to believe that people were pumping up Apple's stock price from 1995 to 2012 because they were waiting for dividends, or hoping for a merger or liquidation? It doesn't seem plausible to me, especially since after Apple announced dividends that year, Apple stock ended up taking a deep dive, despite Wall Street analysts stating the company was doing better than ever. That the stock price reflects expectations of the future cash flows from the stock is a thinly-disguised form of the Efficient Market Hypothesis (EMH), and there's a lot of evidence contrary to the EMH (see references in the previously-linked survey). If you believe what happened in Apple's case was just a rational re-evaluation of Apple stock, then I think you must be a hard-core EMH advocate. Basically (and this is elaborated at length in the survey above), fundamentals and market pricing can become decoupled. This is because there are frictions in the marketplace making it difficult for people to take advantage of the mispricing. In some cases, this can go on for extended periods of time, possibly even years. Part of the friction is caused by strong beliefs by market participants which can often shift pressure to supply or demand. Two popular sayings on Wall Street are, \"\"It doesn't matter if you're right. You have to be right at the right time.\"\" and \"\"It doesn't matter if you're right, if the market disagrees with you.\"\" They suggest that you can make the right decision with where to put your money, but being \"\"right\"\" isn't what drives prices. The market does what it does, and it's subject to the whims of its participants.\"",
"title": ""
},
{
"docid": "334162",
"text": "Here is an example for you. We have a fictional company. It's called MoneyCorp. Its job is to own money, and that's all. Right now it owns $10,000. It doesn't do anything special with that $10,000 - it stores it in a bank account, and whenever it earns interest gives it to the shareholders as a dividend. Also, it doesn't have any expenses at all, and doesn't pay taxes, and is otherwise magic so that it doesn't have to worry about distractions from its mathematical perfection. There are 10,000 shares of MoneyCorp, each worth exactly $1. However, they may trade for more or less than $1 on the stock market, because it's a free market and people trading stock on the stock market can trade at whatever price two people agree on. Scenario 1. MoneyCorp wants to expand. They sell 90,000 shares for $1 each. The money goes in the same bank account at the same interest rate. Do the original shareholders see a change? No. 100,000 shares, $100,000, still $1/share. No problem. This is the ideal situation. Scenario 2: MoneyCorp sells 90,000 shares for less than the current price, $0.50 each. Do the original shareholders lose out? YES. It now has something like $55,000 and 100,000 shares. Each share is now worth $0.55. The company has given away valuable equity to new shareholders. That's bad. Why didn't they get more money from those guys? Scenario 3: MoneyCorp sells 90,000 shares for more than the current price, $2 each, because there's a lot of hype about its business. MoneyCorp now owns $190,000 in 100,000 shares and each share is worth $1.90. Existing shareholders win big! This is why a company would like to make its share offering at the highest price possible (think, Facebook IPO). Of course, the new shareholders may be disappointed. MoneyCorp is actually a lot like a real business! Actually, if you want to get down to it, MoneyCorp works very much like a money-market fund. The main difference between MoneyCorp and a random company on the stock market is that we know exactly how much money MoneyCorp is worth. You don't know that with a real business: sales may grow, sales may drop, input prices may rise and fall, and there's room for disagreement - that's why stock markets are as unpredictable as they are, so there's room for doubt when a company sells their stock at a price existing shareholders think is too cheap (or buys it at a price that is too expensive). Most companies raising capital will end up doing something close to scenario 1, the fair-prices-for-everyone scenario. Legally, if you own part of a company and they do something a Scenario-2 on you... you may be out of luck. Consider also: the other owners are probably hurt as much as you are. Only the new shareholders win. And unless the management approving the deal is somehow giving themselves a sweetheart deal, it'll be hard to demonstrate any malfeasance. As an individual, you probably won't file a lawsuit either, unless you own a very large stake in the company. Lawsuits are expensive. A big institutional investor or activist investor of some sort may file a suit if millions of dollars are at stake, but it'll be ugly at best. If there's nothing evil going on with the management, this is just one way that a company loses money from bad management. It's probably not the most important one to worry about.",
"title": ""
},
{
"docid": "574319",
"text": "My answer is not specific, or even maybe applicable, to Microsoft. Companies don't want to cut dividends. So they have a fixed expense, but the cashflow that funds it might be quite lumpy, or cyclical, depending on the industry. Another, more general, issue is that taking on debt to retire shares is a capital allocation decision. A company needs capital to operate. This is why they went public in the first place, to raise capital. Debt is a cheaper form of capital than equity. Equity holders are last in line in a bankruptcy. Bondholders are at the front of the line. To compensate for this, equity holders require a larger return -- often called a hurdle rate. So why doesn't a company just use cheaper equity, and no debt? Some do. But consider that equity holders participate in the earnings, where bondholders just get the interest, nothing more. And because lenders don't participate in the potential upside, they introduce conditions (debt covenants) to help control their downside exposure. For a company, it's a balance, very much the same as personal finances. A reasonable amount of debt provides low-cost capital, which can be used to produce greater returns. But too much debt, and the covenants are breached, the debt is called due immediately, there's no cash to cover, and wham! bankruptcy. A useful measure, if a bit difficult to calculate, is a company's cost of capital, and the return on that capital. Cost of capital is a blended number taking both equity and debt into account. Good companies earn a return that is greater than their cost of capital. Seems obvious, but many companies don't succeed at this. In cases where this is persistent, the best move for shareholders would be for the company to dissolve and return all the capital. Unfortunately, as in the Railroad Tycoon example above, managers' incentives aren't always well aligned with shareholders, and they allocate capital in ways advantageous to themselves, and not the company.",
"title": ""
},
{
"docid": "414505",
"text": "\"The key difference I've found between a stock split and a stock dividend – of the exact same stock and class, as opposed to a spin-off – seems to be from the company's own accounting perspective. There doesn't appear to be any actual transfer of value to the shareholder with either kind of transaction; i.e. in theory, each transaction would be immaterial to the value of your holdings. With respect to the company's accounting, a stock split affects the par value of the shares, whereas a stock dividend reduces the retained earnings account in order to increase paid-in or contributed capital. I found a good online source which explains the history behind this accounting difference: McGraw-Hill - Intermediate Accounting eBook, 6/e - Chapter 18 - Stock Dividends and Splits. Small quote: [...] Besides being based on fallacious reasoning, accounting for stock dividends by artificially reclassifying “earned” capital as “invested” capital conflicts with the reporting objective of reporting shareholders' equity by source. Despite these limitations, this outdated accounting standard still applies. Since neither the corporation nor its shareholders apparently benefits from stock dividends, why do companies declare them?23 Occasionally, a company tries to give shareholders the illusion that they are receiving a real dividend. Another reason is merely to enable the corporation to take advantage of the accepted accounting practice of capitalizing retained earnings. Specifically, a company might wish to reduce an existing balance in retained earnings—otherwise available for cash dividends—so it can reinvest the earned assets represented by that balance without carrying a large balance in retained earnings. [...] There's a lot more on that page, before and after, worth reading. From another book: Google Books - Comparative Income Taxation, a Structural Analysis - page 314 - Stock Dividends. Small quote: The distribution of dividends in the form of stock or \"\"bonus\"\" shares to existing shareholders typically involves a transfer for corporate law purposes of retained earnings into stated capital. It can been [sic] viewed as a deemed distribution of a cash dividend to the shareholders followed by a corresponding contribution to capital or as solely as an event at the corporate level which has no effect on the shareholders whose economic interest in the corporation is unchanged by the receipt of additional shares. The systems have taken varied approaches to the stock dividend problem. The treatment is in part a function of the rules dealing with distributions of stated capital. [emphases above are mine] [... continues w/descriptions of different countries' tax treatments of the kinds of stock dividends. Includes U.S., Sweden, Japan, Netherlands, Canada, Australia, U.K., France, Germany. ...] As far as why a corporation might want to capitalize earnings and reduce the equity otherwise available for dividends, I can only imagine that, ignoring taxes for a moment, that it may have something to do with capital ratios that need to be maintained for financing or regulatory purposes? Yet, I remain curious. If I discover more on this then I'll update my answer. Additional resources:\"",
"title": ""
},
{
"docid": "330900",
"text": "\"You sold $10,000 worth of stock so that money is essentially yours. However, you sold this stock without actually owning any which means that you, through your broker, are currently borrowing shares amounting to (at the time of your sale) $10,000 from someone who actually owns this stock. You will be paying this person interest for the privilege of borrowing their shares, the exact amount charged varies wildly and depends on factors such as short interest in the stock (loads of people want to go short = shareholders can charge high interest) etc. If I remember correctly hovering over the \"\"position\"\" column in your portfolio in the IB Workstation should give you information about the interest rate charged. You will have to buy back these shares from the lender at some point which is why the $10k isn't just \"\"free money.\"\" If the stock has gone up in price in the meantime you are going to be paying more than the $10k you got for the same amount of shares and vice versa.\"",
"title": ""
},
{
"docid": "324779",
"text": "In fact markets are not efficient and participants are not rational. That is why we have booms and busts in markets. Emotions and psychology play a role when investors and/or traders make decisions, sometimes causing them to behave in unpredictable or irrational ways. That is why stocks can be undervalued or overvalued compared to their true value. Also, different market participants may put a different true value on a stock (depending on their methods of analysis and the information they use to base their analysis on). This is why there are always many opportunities to profit (or lose your money) in liquid markets. Doing your research, homework, or analysis can be related to fundamental analysis, technical analysis, or a combination of the two. For example, you could use fundamental analysis to determine what to buy and then use technical analysis to determine when to buy. To me, doing your homework means to get yourself educated, to have a plan, to do your analysis (both FA and TA), to invest or trade according to your plan and to have a risk management strategy in place. Most people are too lazy to do their homework so will pay someone else to do it for them or they will just speculate (on the latest hot tip) and lose most of their money.",
"title": ""
},
{
"docid": "140481",
"text": "Fully paid up Shares issued in which no more money is required to be paid to the company by shareholders on the value of the shares. When a company issues shares upon incorporation or through an issuance, either initial or secondary, shareholders are required to pay a set amount for those shares. Once the company has received the full amount from shareholders, the shares become fully paid shares. authorised share capital The number of stock units that a publicly traded company can issue as stated in its articles of incorporation, or as agreed upon by shareholder vote. Authorized share capital is often not fully used by management in order to leave room for future issuance of additional stock in case the company needs to raise capital quickly. Another reason to keep shares in the company treasury is to retain a controlling interest in the company. If so, why not just give the existing shareholders the $500 million, (and do a stock split if desired)? Stock splits, bonus issues doesn't generate any capital for the firm, which it required.",
"title": ""
},
{
"docid": "433806",
"text": "\"1) Are the definitions for capital market from the two sources the same? Yes. They are from two different perspectives. Investopedia is looking at it primarily from the perspective of a trader and they lead-off with the secondary market. This refers to the secondary market: A market in which individuals and institutions trade financial securities. This refers to the primary market: Organizations/institutions in the public and private sectors also often sell securities on the capital markets in order to raise funds. Also, the Investopedia definition leaves much to be desired, but it is supposed to be pithy. So, you are comparing apples and oranges, to some extent. One is an article, as short as it may be, this other one is an entry in a dictionary. 2) What is the opposite of capital market, according to the definition in investopedia? It's not quite about opposites, this is not physics. However, that is not the issue here. The Investopedia definition simply does not mention any other possibilities. The Wikipedia article defines the term more thoroughly. It talks about primary/secondary markets in separate paragraph. 3) According to the Wikipedia's definition, why does stock market belong to capital market, given that stocks can be held less than one year too? If you follow the link in the Wikipedia article to money market: As money became a commodity, the money market is nowadays a component of the financial markets for assets involved in short-term borrowing, lending, buying and selling with original maturities of one year or less. The key here is original maturities of one year or less. Here's my attempt at explaining this: Financial markets are comprised of money markets and capital markets. Money is traded as if it were a commodity on the money markets. Hence, the short-term nature in its definition. They are more focused on the money itself. Capital markets are focused on the money as a means to an end. Companies seek money in these markets for longer terms in order to improve their business in some way. A business may go to the money markets to access money quickly in order to deal with a short-term cash crunch. Meanwhile, a business may go to the capital markets to seek money in order to expand its business. Note that capital markets came first and money markets are a relatively recent development. Also, we are typically speaking about the secondary (capital) market when we are talking about the stock or bond market. In this market, participants are merely trading among themselves. The company that sought money by issuing that stock/bond certificate is out of the picture at that point and has its money. So, Facebook got its money from participants in the primary market: the underwriters. The underwriters then turned around and sold that stock in an IPO to the secondary market. After the IPO, their stock trades on the secondary market where you or I have access to trade it. That money flows between traders. Facebook got its money at the \"\"beginning\"\" of the process.\"",
"title": ""
},
{
"docid": "404529",
"text": "\"I understand you make money by buying low and selling high. You can also make money by buying high and selling higher, short selling high and buying back low, short selling low and buying back even lower. An important technique followed by many technical traders and investors is to alway trade with the trend - so if the shares are trending up you go long (buy to open and sell to close); if the shares are trending down you go short (sell to open and buy to close). \"\"But even if the stock price goes up, why are we guaranteed that there is some demand for it?\"\" There is never any guarantees in investing or trading. The only guarantee in life is death, but that's a different subject. There is always some demand for a share or else the share price would be zero or it would never sell, i.e zero liquidity. There are many reasons why there could be demand for a rising share price - fundamental analysis could indicated that the shares are valued much higher than the current price; technical analysis could indicate that the trend will continue; greed could get the better of peoples' emotion where they think all my freinds are making money from this stock so I should buy it too (just to name a few). \"\"After all, it's more expensive now.\"\" What determines if a stock is expensive? As Joe mentioned, was Apple expensive at $100? People who bought it at $50 might think so, but people who bought at $600+ would think $100 is very cheap. On the other hand a penny stock may be expensive at $0.20. \"\"It would make sense if we can sell the stock back into the company for our share of the earnings, but why would other investors want it when the price has gone up?\"\" You don't sell your stocks back to the company for a share of the earnings (unless the company has a share-buy-back arrangement in place), you get a share of the earnings by getting the dividends the company distributes to shareholders. Other investor would want to buy the stock when the price has gone up because they think it will go up further and they can make some money out of it. Some of the reasons for this are explained above.\"",
"title": ""
},
{
"docid": "11311",
"text": "\"Why only long term investments? What do they care if I buy and sell shares in a company in the same year? Simple, your actually investing when you hold it for a long term. If you hold a stock for a week or a month there is very little that can happen to change the price, in a perfect market the value of a company should stay the same from yesterday to today so long as there is no news(a perfect market cannot exist). When you hold a stock for a long term you really are investing in the company and saying \"\"this company will grow\"\". Short term investing is mostly speculation and speculation causes securities to be incorrectly valued. So when a retail investor puts money into something like Facebook for example they can easily be burned by speculation whether its to the upside or downside. If the goal is to get me to invest my money, then why not give apply capital gains tax to my savings account at my local bank? Or a CD account? I believe your gains on these accounts are taxed... Not sure at what rate. If the goal is to help the overall health of business, how does it do that? During an IPO, the business certainly raises money, but after that I'm just buying and selling shares with other private shareholders. Why does the government give me an incentive to do this (and then hold onto it for at least a year)? There are many reasons why a company cares about its market price: A companies market cap is calculated by price * shares outstanding. A market cap is basically what the market is saying your company is worth. A company can offer more shares or sell shares they currently hold in order to raise even more capital. A company can offer shares instead of cash when buying out another company. It can pay for many things with shares. Many executives and top level employees are payed with stock options, so they defiantly want to see there price higher. these are some basic reasons but there are more and they can be more complex.\"",
"title": ""
},
{
"docid": "153212",
"text": "Why is the stock trading at only $5 per share? The share price is the perceived value of the company by people buying and selling the stock. Not the actual value of the company and all its assets. Generally if the company is not doing well, there is a perceived risk that it will burn out the money fast. There is a difference between its signed conditional sale and will get money and has got money. So in short, it's trading at $5 a share because the market doesn't feel like it's worth $12 per share. Quite a few believe there could be issues faced; i.e. it may not make the $12, or there will be additional obligations, i.e. employees may demand more layoff compensation, etc. or the distribution may take few years due to regulatory and legal hurdles. The only problem is the stock exchange states if the company has no core business, the stock will be suspended soon (hopefully they can release the $12 per share first). What will happen if I hold shares in the company, the stock gets suspended, and its sitting on $12 per share? Can it still distribute it out? Every country and stock markets have laid out procedures for de-listing a company and closing a company. The company can give $10 as say dividends and remaining later; or as part of the closure process, the company will distribute the balance among shareholders. This would be a long drawn process.",
"title": ""
},
{
"docid": "48188",
"text": "449 of the 500 companies in the S&P 500 used 54% of their earnings to buy back shares for over $2 trillion. Rather than invest in development, capital, human capital, bigger dividends, they're repurchasing shares to boost their EPS and increase share value in the short term. Why is this an issue? Because it shows that these companies are uneasy about the long term. It stunts growth. Doesn't have to be research, simply expansion or rewarding employees/shareholders. Employees of the company receive no benefits and bagholders may make a quick buck short term, but suffer long. Execs of the company however get fat AF checks for hitting target ratios and price. Stock buybacks enable this.",
"title": ""
},
{
"docid": "71614",
"text": "\">As a legal matter, shareholders who purchase shares of stock in a corporation own nothing more than that—shares of stock. Similarly, bondholders own only bonds, and executives with employment contracts own their contracts. None of these types of ownership give shareholders, bondholders or executives the right to control the firm. The right to control the firm’s assets and actions rests in the hands of its board of directors, and only when they act as a body and follow proper board procedures. All this says is \"\"decisions are made by the board.\"\" This is not news, and it doesn't mean that shareholders do not own the company. Shareholders elect the board, by the way. >An important consequence of this governance structure is that shareholders not only have no legal right to control the firm, they also have no legal right to help themselves to the corporation’s assets. Well, that's wrong. >In fact, the only time shareholders receive any funds directly from the corporation’s coffers is when they receive a dividend or the corporation repurchases their shares. Or, you know, in the case of bankruptcy. >This only happens when the directors vote to declare a dividend or a corporate repurchase. The same directors who were appointed by shareholders. >At law, a principal has a right to control her agent. But shareholders can’t exercise direct control over corporate directors. I suppose this is true in the sense that shareholders cannot practice slavery. But shareholders can, again, vote on issues relating to the governance of the company. >It is thus wildly misleading to describe shareholders as the sole residual claimants in companies that aren’t actually in bankruptcy. This is only true if you're retarded and don't know what \"\"residual\"\" means. >This idea is supported by modern options theory. In effect, bondholders own the right to access cash flow but have sold a call to shareholders, while shareholders own the right to access the cash flow but have sold a put to bondholders. Neither shareholders nor bondholders can claim an exclusive right to “own” the company’s cash flow, much less the company. This is a made up explanation that doesn't mean anything. The real options model of corporate assets is that corporate debt is a risk-free bond with a short put option and equity is a call option. There is no \"\"deal,\"\" in actuality or in spirit, between debt and equity owners. You can dismiss the article as \"\"shit.\"\"\"",
"title": ""
},
{
"docid": "354638",
"text": "\"This is an excellent question, one that I've pondered before as well. Here's how I've reconciled it in my mind. Why should we agree that a stock is worth anything? After all, if I purchase a share of said company, I own some small percentage of all of its assets, like land, capital equipment, accounts receivable, cash and securities holdings, etc., as others have pointed out. Notionally, that seems like it should be \"\"worth\"\" something. However, that doesn't give me the right to lay claim to them at will, as I'm just a (very small) minority shareholder. The old adage says that \"\"something is only worth what someone is willing to pay you for it.\"\" That share of stock doesn't actually give me any liquid control over the company's assets, so why should someone else be willing to pay me something for it? As you noted, one reason why a stock might be attractive to someone else is as a (potentially tax-advantaged) revenue stream via dividends. Especially in this low-interest-rate environment, this might well exceed that which I might obtain in the bond market. The payment of income to the investor is one way that a stock might have some \"\"inherent value\"\" that is attractive to investors. As you asked, though, what if the stock doesn't pay dividends? As a small shareholder, what's in it for me? Without any dividend payments, there's no regular method of receiving my invested capital back, so why should I, or anyone else, be willing to purchase the stock to begin with? I can think of a couple reasons: Expectation of a future dividend. You may believe that at some point in the future, the company will begin to pay a dividend to investors. Dividends are paid as a percentage of a company's total profits, so it may make sense to purchase the stock now, while there is no dividend, banking on growth during the no-dividend period that will result in even higher capital returns later. This kind of skirts your question: a non-dividend-paying stock might be worth something because it might turn into a dividend-paying stock in the future. Expectation of a future acquisition. This addresses the original premise of my argument above. If I can't, as a small shareholder, directly access the assets of the company, why should I attribute any value to that small piece of ownership? Because some other entity might be willing to pay me for it in the future. In the event of an acquisition, I will receive either cash or another company's shares in compensation, which often results in a capital gain for me as a shareholder. If I obtain a capital gain via cash as part of the deal, then this proves my point: the original, non-dividend-paying stock was worth something because some other entity decided to acquire the company, paying me more cash than I paid for my shares. They are willing to pay this price for the company because they can then reap its profits in the future. If I obtain a capital gain via stock in as part of the deal, then the process restarts in some sense. Maybe the new stock pays dividends. Otherwise, perhaps the new company will do something to make its stock worth more in the future, based on the same future expectations. The fact that ownership in a stock can hold such positive future expectations makes them \"\"worth something\"\" at any given time; if you purchase a stock and then want to sell it later, someone else is willing to purchase it from you so they can obtain the right to experience a positive capital return in the future. While stock valuation schemes will vary, both dividends and acquisition prices are related to a company's profits: This provides a connection between a company's profitability, expectations of future growth, and its stock price today, whether it currently pays dividends or not.\"",
"title": ""
},
{
"docid": "241175",
"text": "Can a company not bargain with a dying company for example and buy a falling stock at lower than market value? Of course. If the shareholders agree to it. But why would they, if the market value is higher, agree to sell to someone who offers less? If there's a compelling reason - it can happen. It might happen during a hostile takeover, for example. In the case of buying the company for more than market value, are the stocks bought for significantly more, or slightly more than the current market value? Again, depends on how valuable the shareholders think the company is. If the shareholders think that the company has a potential which has not yet affected the stock price, they'll want a higher premium (and they'd think that, otherwise why would they hold the stock?). How much higher? Depends on the bargaining abilities of the sides.",
"title": ""
},
{
"docid": "321108",
"text": "A Breakdown of Stock Buy Backs has this bottom line on it: Are share buybacks good or bad? As is so often the case in finance, the question may not have a definitive answer. If a stock is undervalued and a buyback truly represents the best possible investment for a company, the buyback - and its effects - can be viewed as a positive sign for shareholders. Watch out, however, if a company is merely using buybacks to prop up ratios, provide short-term relief to an ailing stock price or to get out from under excessive dilution. Read more: http://www.investopedia.com/articles/02/041702.asp#ixzz3ZHdOf2dJ What is the reason that a company like AAPL is buying back its own shares? Offsetting dilution would be my main thought here as many employees may exercise options putting more stock out there that the company buys back stock to balance things. Does it have too much cash and it doesn't know what to do with it? No as it could do dividends if it wanted to give it back to investors. So it is returning the cash back to investors? Not quite. While some investors may get cash from Apple, I'd suspect most shareholders aren't likely to see cash unless they are selling their shares so I wouldn't say yes to this without qualification. At the same time, the treasury shares Apple has can be used to give options to employees or be used in acquisitions for a couple of other purposes.",
"title": ""
},
{
"docid": "400983",
"text": "\"A share of stock is a share of the underlying business. If one believes the underlying business will grow in value, then one would expect the stock price to increase commensurately. Participants in the stock market, in theory, assign value based on some combination of factors like capital assets, cash on hand, revenue, cash flow, profits, dividends paid, and a bunch of other things, including \"\"intangibles\"\" like customer loyalty. A dividend stream may be more important to one investor than another. But, essentially, non-dividend paying companies (and, thus, their shares) are expected by their owners to become more valuable over time, at which point they may be sold for a profit. EDIT TO ADD: Let's take an extremely simple example of company valuation: book value, or the sum of assets (capital, cash, etc) and liabilities (debt, etc). Suppose our company has a book value of $1M today, and has 1 million shares outstanding, and so each share is priced at $1. Now, suppose the company, over the next year, puts another $1M in the bank through its profitable operation. Now, the book value is $2/share. Suppose further that the stock price did not go up, so the market capitalization is still $1M, but the underlying asset is worth $2M. Some extremely rational market participant should then immediately use his $1M to buy up all the shares of the company for $1M and sell the underlying assets for their $2M value, for an instant profit of 100%. But this rarely happens, because the existing shareholders are also rational, can read the balance sheet, and refuse to sell their shares unless they get something a lot closer to $2--likely even more if they expect the company to keep getting bigger. In reality, the valuation of shares is obviously much more complicated, but this is the essence of it. This is how one makes money from growth (as opposed to income) stocks. You are correct that you get no income stream while you hold the asset. But you do get money from selling, eventually.\"",
"title": ""
},
{
"docid": "344076",
"text": "The original owner of the shares can pledge their shares to be short, and they earn interest from lending their shares. The conditions of this arrangement are detailed in standard agreements all market participants sign with their broker, or clearinghouse, or with the exchange, or with the self regulatory agency. Stocks within the same class are identical, despite someone's sentiment to an old share certificate that their grandparents gave them, and as such can be sold and returned to the beneficial owner multiple times with no difference. That is how it is supposed to work anyway, as naked shorting involves selling fictional shares that have no beneficial owner. So there are market inefficiencies in this practice, but the agreements between market participants are sound and answers your question about how.",
"title": ""
},
{
"docid": "311153",
"text": "The short answer to your question is yes. Company performance affects stock price only through investors' views. But note that selling for higher and lower prices when the company is doing well or poorly is not an arbitrary choice. A stock is a claim on the future cash flows of the firm, which ultimately come from its future profits. If the company is doing well, investors will likely expect that there will large cash flows (dividends) in the future and be willing to pay more to hold it (or require more to sell it). The price of a stock is equal what people think the future dividends are worth. If market participants started behaving irrationally, like not reacting to changes in the expected future cash flows, then arbitrageurs would make a ton of money trading against them until the situation was rectified.",
"title": ""
},
{
"docid": "228810",
"text": "No, if your stock is called away, the stock is sold at the agreed upon price. You cannot get it back at your original price. If you don't want your stock to be called, make sure you have the short call position closed by expiration if it is ITM. Also you could be at risk for early assignment if the option has little to no extrinsic value, although probably not. But when dividends are coming, make sure you close your short ITM options. If the dividend is worth more than the extrinsic value, you are pretty much guaranteed to be assigned. Been assigned that way too many times. Especially in ETFs where the dividends aren't dates are not always easy to find. It happens typically during triple witching. If you are assigned on your short option, you will be short stock and you will have to pay the dividend to the shareholder of your short stock. So if you have a covered call on, and you are assigned, your stock will be called away, and you will have to pay the dividend.",
"title": ""
},
{
"docid": "217499",
"text": "\"I don't know if it's common or necessary to include capital stock as a liability? Yes, if you look at the title of the nonasset part of the balance sheet it actually is titled \"\"Liabilities and Shareholders' Equity\"\". Your capital stock is a component of Equity. This sounds like it was reported in a reasonable manner. \"\"$2,582 listed under Loans from Shareholders (Line 19).\"\" Did you have a basis issue with your distributions? That is did you take shareholder distributions more than your adjusted basis that you have been taxed on? I have seen the practice of considering distributions in excess of basis as short term loans to prevent the additional taxation of the excess distribution. Be careful when you adjust this entry, your balance sheet had to roll from one year to the next. You must have a reasonable transaction to substantiate the removal of the shareholder loan.\"",
"title": ""
},
{
"docid": "58290",
"text": "The original poster's concern is valid. Sometimes, market orders do get executed at seemingly ridiculous prices. In addition to Victor's reasons for using a market order, sometimes a seller does not care how low the price is. For example, after a company goes broke, its stock continues to trade for a while. This allows shareholders to realize their losses for tax purposes, and allows short-sellers to close out their positions. A shareholder who is trying to realize a 10 dollar per share loss for tax purposes probably does not care whether he gets 10 cents per share or 0.001 cents per share, so a sell-at-market order makes sense.",
"title": ""
},
{
"docid": "484778",
"text": "\"There are a few reason why the stock price decreases after a dividend is paid: What's the point of paying a dividend if the stock price automatically decreases? Don't the shareholders just break even? Companies have to do something with their profits. They beholden to their shareholders to make them money either by increasing the share value or paying dividends. So they have the choice between reinvesting their profits into the company to grow the business or just handing the profits directly to the owners of the business (the shareholders). Some companies are as big as they want to be and investing their profits into more capital offers them diminishing returns. These companies are more likely to pay dividends to their shareholders. I assume the price of the stock \"\"naturally\"\" increases over the year to reflect the amount of the dividend payment. This is kind of a vague question but then doesn't it make it difficult to evaluate the fluctuations in stock price (in the way that you would a company that doesn't pay a dividend)? It depends on the company. The price may recover the dividend drop... could take a few days to a week. And that dependings on the company's performance and the overall market performance. With respect to options, I assume nothing special happens? So say I bought $9 call options yesterday that were in the money, all of a sudden they're just not? Is this typically priced into the option price? Is there anything else I need to know about buying options in companies that pay dividends? What if I had an in-the-money option, and all of a sudden out of nowhere a company decides to pay a dividend for the first time. Am I just screwed? One key is that dividends are announced in advance (typically at least, if not always; not sure if it's required by law but I wouldn't be surprised). This is one reason people will sometimes exercise a call option early, because they want to get the actual stock in order to earn the dividend. For \"\"out of the ordinary\"\" large cash dividends (over 10% is the guideline), stock splits, or other situations an option can be adjusted: http://www.888options.com/help/faq/splits.jsp#3 If you have an options account, they probably sent you a \"\"Characteristics and Risks of Standardized Options\"\" booklet. It has a section discussing this topic and the details of what kinds of situations trigger an adjustment. A regular pre-announced <10% dividend does not, while a special large dividend would, is what I roughly get from it. That \"\"Characteristics and Risks of Standardized Options\"\" is worth reading by the way; it's long and complicated, but well, options are complicated. Finally, do all companies reduce their stock price when they pay a dividend? Are they required to? I'm just shocked I've never heard of this before. The company doesn't directly control the stock price, but I do believe this is automatic. I think the market does this automatically because if they didn't, there would be enough people trying to do dividend capture arbitrage that it would ultimately drive down the price.\"",
"title": ""
},
{
"docid": "411617",
"text": "The same applies if you were looking for a business to buy: would you pay more for a business that is doing well making increasing profits year after year, or for a business that is not doing so well and is losing money. A share in a company is basically a small part of a company which a shareholder can own. So would you rather own a part of a company that is increasing profits year after year or one that is continuously losing money? Someone would buy shares in a company in order to make a better return than they could make elsewhere. They can make a profit through two ways: first, a share of the company's profits through dividends, and second capital gains from the price of the shares going up. Why does the price of the shares go up over the long term when a company does well and increases profits? Because when a company increases profits they are making more and more money which increases the net worth of the company. More investors would prefer to buy shares in a company that makes increasing profits because this will increase the net worth of the company, and in turn will drive the share price higher over the long term. A company's increase in profits creates higher demand for the company's shares. Think about it, if interest rates are so low like they are now, where it is hard to get a return higher than inflation, why wouldn't investors then search for higher returns in good performing companies in the stock market? More investors' and traders' wanting some of the pie, creates higher demand for good performing stocks driving the share price higher. The demand for these companies is there primarily because the companies are increasing their profits and net worth, so over the long term the share price will increase in-line with the net worth. Over the short to medium term other factors can also affect the share price, sometime opposite to how the company is actually performing; however this is a whole different answer to a whole different question.",
"title": ""
},
{
"docid": "11295",
"text": "Yes, it is possible. But why would someone take full responsibility, if you're the one enjoying the profits? You'll have to pay your administrator a lot, and probably also develop a profit sharing plan to encourage success. What you're looking, essentially is to be a passive shareholder, and not participate in any management decisions at all. Depending on your location, it will pose additional disadvantages for you (for example, in the US, that would force you to structure your business as a C-Corp, vs more advantageous S-Corp).",
"title": ""
}
] |
4401
|
Can a non dividend-paying product (say ETF) suddenly start paying dividends?
|
[
{
"docid": "420267",
"text": "Yes, absolutely. Consider Microsoft, Updated Jan. 17, 2003 11:59 p.m. ET Software giant Microsoft Corp., finally bowing to mounting pressure to return some of its huge cash hoard to investors, said it will begin paying a regular annual dividend to shareholders. From Wall Street Journal. Thus, for the years prior to 2003, the company didn't pay dividends but changed that. There can also be some special one-time dividends as Microsoft did the following year according to the Wall Street Journal: The $32 billion one-time dividend payment, which comes to $3 for each share of Microsoft stock, could be a measurable stimulus to the U.S. economy -- and is expected to arrive just in time for holiday shopping. Course companies can also reduce to stop dividends as well.",
"title": ""
}
] |
[
{
"docid": "422295",
"text": "\"In some sense, the share repurchasing program is better if the company does not foresee the same profit levels down the road. Paying a dividend for several years and then suddenly not paying or reducing a dividend is viewed as a \"\"slap in the face\"\" by investors. Executing a share repurchase program one year and then not the next is not viewed as negatively. From an investor's standpoint, I would say a dividend is preferred over a share repurchase program for a similar reason. Typically companies that pay a dividend have been doing so for quite some time and even increasing it over time as the company increases profits. So, it can be assumed that if a company starts paying a dividend, it will do so for the long-run.\"",
"title": ""
},
{
"docid": "192421",
"text": "\"The answer is Discounted Cash Flows. Companies that don't pay dividends are, ostensibly reinvesting their cash at returns higher than shareholders could obtain elsewhere. They are reinvesting in productive capacity with the aim of using this greater productive capacity to generate even more cash in the future. This isn't just true for companies, but for almost any cash-generating project. With a project you can purchase some type of productive assets, you may perform some kind of transformation on the good (or not), with the intent of selling a product, service, or in fact the productive mechanism you have built, this productive mechanism is typically called a \"\"company\"\". What is the value of such a productive mechanism? Yes, it's capacity to continue producing cash into the future. Under literally any scenario, discounted cash flow is how cash flows at distinct intervals are valued. A company that does not pay dividends now is capable of paying them in the future. Berkshire Hathaway does not pay a dividend currently, but it's cash flows have been reinvested over the years such that it's current cash paying capacity has multiplied many thousands of times over the decades. This is why companies that have never paid dividends trade at higher prices. Microsoft did not pay dividends for many years because the cash was better used developing the company to pay cash flows to investors in later years. A companies value is the sum of it's risk adjusted cash flows in the future, even when it has never paid shareholders a dime. If you had a piece of paper that obligated an entity (such as the government) to absolutely pay you $1,000 20 years from now, this $1,000 cash flows present value could be estimated using Discounted Cash Flow. It might be around $400, for example. But let's say you want to trade this promise to pay before the 20 years is up. Would it be worth anything? Of course it would. It would in fact typically go up in value (barring heavy inflation) until it was worth very close to $1,000 moments before it's value is redeemed. Imagine that this \"\"promise to pay\"\" is much like a non-dividend paying stock. Throughout its life it has never paid anyone anything, but over the years it's value goes up. It is because the discounted cash flow of the $1,000 payout can be estimated at almost anytime prior to it's payout.\"",
"title": ""
},
{
"docid": "290831",
"text": "The catch is that you're doing a form of leveraged investing. In other words, you're gambling on the stock market using money that you've borrowed. While it's not as dangerous as say, getting money from a loan shark to play blackjack in Vegas, there is always the chance that markets can collapse and your investment's value will drop rapidly. The amount of risk really depends on what specific investments you choose and how diversified they are - if you buy only Canadian stocks then you're at risk of losing a lot if something happened to our economy. But if your Canadian equities only amount to 3.6% of your total (which is Canada's share of the world market), and you're holding stocks in many different countries then the diversification will reduce your overall risk. The reason I mention that is because many people using the Smith Maneuver are only buying Canadian high-yield dividend stocks, so that they can use the dividends to accelerate the Smith Maneuver process (use the dividends to pay down the mortgage, then borrow more and invest it). They prefer Canadian equities because of preferential tax treatment of the dividend income (in non-registered accounts). But if something happened to those Canadian companies, they stand to lose much of the investment value and suddenly they have the extra debt (the amount borrowed from a HELOC, or from a re-advanceable mortgage) without enough value in the investments to offset it. This could mean that they will not be able to pay off the mortgage by the time they retire!",
"title": ""
},
{
"docid": "266944",
"text": "\"Yes, I agree with you. Saying that the value of the stock will grow as the company grows and acquires more assets ... I don't see why. Okay, I'm a nice guy and I want to see other people do well, but what do I care how much money they're making if they're not giving any of it to ME? Frankly I think it's like people who buy commemorative plates or beanie babies or other \"\"collectibles\"\" as an investment. As long as others are also buying them as an investment, and buying and reselling at a profit, the value will continue to go up. But one day people say, Wait, is this little stuffed toy really worth $10,000? and the balloon bursts. Confer Dutch tulips: http://www.damninteresting.com/the-dutch-tulip-bubble-of-1637/ As I see it, what gives a non-dividend-paying stock value is mostly the expectation that at some time in the future it will pay dividends. This is especially true of new start-up companies. As you mentioned, there's also the possibility of a takeover. It wouldn't have to be a hostile takeover, any takeover would do. At that point the buying company either buys the stock or exchanges it for shares of their own. In the first case you now have cash for your investment and in the second case you now have stock in a dividend-paying company -- or in another non-dividend-paying company and you start the cycle over.\"",
"title": ""
},
{
"docid": "437907",
"text": "The dividend tax credit is not applicable to foreign dividend income, so you would be taxed fully on every dollar of that income. When you sell a stock, there will be a capital gain or capital loss depending on if it gained or lost value, after accounting for the Adjusted Cost Base. You only pay income tax on half of the amount earned through capital gains, and if you have losses, you can use them to offset other investments that had capital gains (or carry forward to offset gains in the future). The dividends from US stocks are subject to a 15% withholding tax that gets paid to the IRS automatically when the dividends are issued. If the stocks are held in an RRSP, they are exempt from the withholding tax. If held in a non-registered account, you can be reimbursed for the tax by claiming the foreign tax credit that you linked to. If held in a TFSA or RESP, the withholding tax cannot be recovered. Also, if you are not directly holding the stocks, and instead buy a mutual fund or ETF that directly holds the stocks, then the RRSP exemption no longer applies, but the foreign tax credit is still claimable for a non-registered account. If the mutual fund or ETF does not directly hold stocks, and instead holds one or more ETFs, there is no way to recover the withholding tax in any type of account.",
"title": ""
},
{
"docid": "63296",
"text": "\"If so, then if company A never pays dividends to its shareholders, then what is the point of owning company A's stock? The stock itself can go up in price. This is not necessarily pure speculation either, the company could just reinvest the profits and grow. Since you own part of a company, your share would also increase in value. The company could also decide to start paying dividend. I think one rule of thumb is that growing companies won't pay out, since they reinvest all profit to grow even more, but very large companies like McDonalds or Microsoft who don't really have much room left to grow will pay dividends more. Surely the right to one vote for company A's Board can't be that valuable. Actually, Google for instance neither pays dividend nor do you get to vote. Basically all you get for your money is partial ownership of the company. This still gives you the right to seize Google assets if you go bankrupt, if there's any asset left once the creditors are done (credit gets priority over equity). What is it that I'm missing? What you are missing is that the entire concept of the dividend is an illusion. There's little qualitative difference between a stock that pays dividend, and a stock that doesn't. If you were going to buy the stock, then hold it forever and collect dividend, you could get the same thing with a dividend-less stock by simply waiting for it to gain say 5% value, then sell 4.76% of your stock and call the cash your dividend. \"\"But wait,\"\" you say, \"\"that's not the same - my net worth has decreased!\"\" Guess what, stocks that do pay dividend usually do drop in value right after the pay out, and they drop by about the relative value of the dividend as well. Likewise, you could take a stock that does pay dividend, and make it look exactly like a non-paying stock by simply taking every dividend you get and buying more of the same stock with it. So from this simplistic point of view, it is irrelevant whether the stock itself pays dividend or not. There is always the same decision of whether to cut the goose or let it lay a few more eggs that every shareholder has to make it. Paying a dividend is essentially providing a different default choice, but makes little difference with regards to your choices. There is however more to it than simple return on investment arithmetic: As I said, the alternative to paying dividend is reinvesting profits back into the enterprise. If the company decided to pay out dividend, that means they think all the best investing is done, and they don't really have a particularly good idea for what to do with the extra money. Conversely, not paying is like management telling the shareholders, \"\"no we're not done, we're still building our business!\"\". So it can be a way of judging whether the company is concentrating on generating profit or growing itself. Needless to say the, the market is wild and unpredictable and not everyone obeys such assumptions. Furthermore, as I said, you can effectively overrule the decision by increasing or decreasing your position, regardless of whether they have decided to pay dividend to begin with. Lastly, there may be some subtle differences with regards to things like how the income is taxed and so on. These don't really have much to do with the market itself, but the bureaucracy tacked onto the market.\"",
"title": ""
},
{
"docid": "352484",
"text": "\"In financial theory, there is no reason for a difference in investor return to exist between dividend paying and non-dividend paying stocks, except for tax consequences. This is because in theory, a company can either pay dividends to investors [who can reinvest the funds themselves], or reinvest its capital and earn the same return on that reinvestment [and the shareholder still has the choice to sell a fraction of their holdings, if they prefer to have cash]. That theory may not match reality, because often companies pay or don't pay dividends based on their stage of life. For example, early-stage mining companies often have no free cashflow to pay dividends [they are capital intensive until the mines are operational]. On the other side, longstanding companies may have no projects left that would be a good fit for further investment, and so they pay out dividends instead, effectively allowing the shareholder to decide where to reinvest the money. Therefore, saying \"\"dividend paying\"\"/\"\"growth stock\"\" can be a proxy for talking about the stage of life + risk and return of a company. Saying dividend paying implies \"\"long-standing blue chip company with relatively low capital requirements and a stable business\"\". Likewise \"\"growth stocks\"\" [/ non-dividend paying] implies \"\"new startup company that still needs capital and thus is somewhat unproven, with a chance for good return to match the higher risk\"\". So in theory, dividend payment policy makes no difference. In practice, it makes a difference for two reasons: (1) You will most likely be taxed differently on selling stock vs receiving dividends [Which one is better for you is a specific question relying on your jurisdiction, your current income, and things like what type of stock / how long you hold it]. For example in Canada, if you earn ~ < $40k, your dividends are very likely to have a preferential tax treatment to selling shares for capital gains [but your province and specific other numbers would influence this]. In the United States, I believe capital gains are usually preferential as long as you hold the shares for a long time [but I am not 100% on this without looking it up]. (2) Dividend policy implies differences in the stage of life / risk level of a stock. This implication is not guaranteed, so be sure you are using other considerations to determine whether this is the case. Therefore which dividend policy suits you better depends on your tax position and your risk tolerance.\"",
"title": ""
},
{
"docid": "281841",
"text": "\"The amount, reliability and frequency of dividends paid by an ETF other than a stock, such as an index or mutual fund, is a function of the agreement under which the ETF was established by the managing or issuing company (or companies), and the \"\"basket\"\" of investments that a share in the fund represents. Let's say you invest in a DJIA-based index fund, for instance Dow Diamonds (DIA), which is traded on several exchanges including NASDAQ and AMEX. One share of this fund is currently worth $163.45 (Jan 22 2014 14:11 CDT) while the DJIA itself is $16,381.38 as of the same time, so one share of the ETF represents approximately 1% of the index it tracks. The ETF tracks the index by buying and selling shares of the blue chips proportional to total invested value of the fund, to maintain the same weighted percentages of the same stocks that make up the index. McDonald's, for instance, has an applied weight that makes the share price of MCD stock roughly 5% of the total DJIA value, and therefore roughly 5% of the price of 100 shares of DIA. Now, let's say MCD issued a dividend to shareholders of, say, $.20 per share. By buying 100 shares of DIA, you own, through the fund, approximately five MCD shares, and would theoretically be entitled to $1 in dividends. However, keep in mind that you do not own these shares directly, as you would if you spent $16k buying the correct percentage of all the shares directly off the exchange. You instead own shares in the DIA fund, basically giving you an interest in some investment bank that maintains a pool of blue-chips to back the fund shares. Whether the fund pays dividends or not depends on the rules under which that fund was set up. The investment bank may keep all the dividends itself, to cover the expenses inherent in managing the fund (paying fund management personnel and floor traders, covering losses versus the listed price based on bid-ask parity, etc), or it may pay some percentage of total dividends received from stock holdings. However, it will virtually never transparently cut you a check in the amount of your proportional holding of an indexed investment as if you held those stocks directly. In the case of the DIA, the fund pays dividends monthly, at a yield of 2.08%, virtually identical to the actual weighted DJIA yield (2.09%) but lower than the per-share mean yield of the \"\"DJI 30\"\" (2.78%). Differences between index yields and ETF yields can be reflected in the share price of the ETF versus the actual index; 100 shares of DIA would cost $16,345 versus the actual index price of 16,381.38, a delta of $(36.38) or -0.2% from the actual index price. That difference can be attributed to many things, but fundamentally it's because owning the DIA is not the exact same thing as owning the correct proportion of shares making up the DJIA. However, because of what index funds represent, this difference is very small because investors expect to get the price for the ETF that is inherent in the real-time index.\"",
"title": ""
},
{
"docid": "480808",
"text": "Let me answer by parts: When a company gives dividends, the share price drops by the dividend amount. Not always by that exact amount for many different reasons (e.g. there are transaction costs if you reinvest, dividend taxes, etc). I have tested that empirically. Now, if all the shareholders choose to reinvest their dividends, will the share price go back up to what it was prior to the dividend? That is an interesting question. The final theoretical price of the company does not need to be that. When a company distributes dividends its liquidity diminish, there is an impact on the balance sheet of the company. If all investors go to the secondary market and reinvest the dividends in the shares, that does not restore the cash in the balance sheet of the company, hence the theoretical real value of the company is different before the dividends. Of course, in practice there is not such a thing as one theoretical value. In reality, if everybody reinvest the dividend, that will put upward pressure over the price of the company and, depending on the depth of the offers, meaning how many orders will counterbalance the upward pressure at the moment, the final price will be determined, which can be higher or lower than before, not necessarily equal. I ask because some efts like SPY automatically reinvest dividends. So what is the effect of this reinvestment on the stock price? Let us see the mechanics of these purchases. When a non distributing ETF receives cash from the dividends of the companies, it takes that cash and reinvest it in the whole basket of stocks that compose the index, not just in the companies that provided the dividends. The net effect of that is a small leverage effect. Let us say you bought one unit of SPY, and during the whole year the shares pay 2% of dividends that are reinvested. At the end of that year, it will be equivalent to having 1.02 units of SPY.",
"title": ""
},
{
"docid": "495600",
"text": "\"Question 1: How do I start? or \"\"the broker\"\" problem Get an online broker. You can do a wire transfer to fund the account from your bank. Question 2: What criticism do you have for my plan? Dividend investing is smart. The only problem is that everyone's currently doing it. There is an insatiable demand for yield, not just individual investors but investment firms and pension funds that need to generate income to fund retirements for their clients. As more investors purchase the shares of dividend paying securities, the share price goes up. As the share price goes up, the dividend yield goes down. Same for bonds. For example, if a stock pays $1 per year in dividends, and you purchase the shares at $20/each, then your yearly return (not including share price fluctuations) would be 1/20 = 5%. But if you end up having to pay $30 per share, then your yearly return would be 1/30 or 3.3% yield. The more money you invest, the bigger this difference becomes; with $100K invested you'd make about $1.6K more at 5%. (BTW, don't put all your money in any small group of stocks, you want to diversify). ETFs work the same way, where new investors buying the shares cause the custodian to purchase more shares of the underlying securities, thus driving up the price up and yield down. Instead of ETFs, I'd have a look at something called closed end funds, or CEFs which also hold an underlying basket of securities but often trade at a discount to their net asset value, unlike ETFs. CEFs usually have higher yields than their ETF counterparts. I can't fully describe the ins and outs here in this space, but you'll definately want to do some research on them to better understand what you're buying, and HOW to successfully buy (ie make sure you're buying at a historically steep discount to NAV [https://seekingalpha.com/article/1116411-the-closed-end-fund-trifecta-how-to-analyze-a-cef] and where to screen [https://www.cefconnect.com/closed-end-funds-screener] Regardless of whether you decide to buy stocks, bonds, ETFs, CEFs, sell puts, or some mix, the best advice I can give is to a) diversify (personally, with a single RARE exception, I never let any one holding account for more than 2% of my total portfolio value), and b) space out your purchases over time. b) is important because we've been in a low interest rate environment since about 2009, and when the risk free rate of return is very low, investors purchase stocks and bonds which results in lower yields. As the risk free rate of return is expected to finally start slowly rising in 2017 and gradually over time, there should be gradual downward pressure (ie selling) on the prices of dividend stocks and especially bonds meaning you'll get better yields if you wait. Then again, we could hit a recession and the central banks actually lower rates which is why I say you want to space your purchases out.\"",
"title": ""
},
{
"docid": "360716",
"text": "\"What you seem to want is a dividend reinvestment plan (DRIP). That's typically offered by the broker, not by the ETF itself. Essentially this is a discounted purchase of new shares when you're dividend comes out. As noted in the answer by JoeTaxpayer, you'll still need to pay tax on the dividend, but that probably won't be a big problem unless you've got a lot of dividends. You'll pay that out of some other funds when it's due. All DRIPs (not just for ETFs) have potential to complicate computation of your tax basis for eventual sale, so be aware of that. It doesn't have to be a show-stopper for you, but it's something to consider before you start. It's probably less of a problem now than it used to be since brokers now have to report your basis on the 1099-B in the year of sale, reducing your administrative burden (if you trust them to get it right). Here's a list of brokerages that were offering this from a top-of-the-search-list article that I found online: Some brokerages, including TD Ameritrade, Vanguard, Scottrade, Schwab and, to a lesser extent, Etrade, offer ETF DRIPs—no-cost dividend reinvestment programs. This is very helpful for busy clients. Other brokerages, such as Fidelity, leave ETF dividend reinvestment to their clients. Source: http://www.etf.com/sections/blog/23595-your-etf-has-drip-drag.html?nopaging=1 Presumably the list is not constant. I almost didn't included but I thought the wide availability (at least as of the time of the article's posting) was more interesting than any specific broker on it. You'll want to do some research before you choose a broker to do this. Compare fees for sure, but also take into account other factors like how soon after the dividend they do the purchase (is it the ex-date, the pay date, or something else?). A quick search online should net you several decent articles with more information. I just searched on \"\"ETF DRIP\"\" to check it out.\"",
"title": ""
},
{
"docid": "459953",
"text": "As far as I read in many articles, all earnings (capital gains and dividends) from Canadian stocks will be always tax-free. Right? There's no withholding tax, ie. a $100 dividend means you get $100. There's no withholding for capital gains in shares for anybody. You will still have to pay taxes on the amounts, but that's only due at tax time and it could be very minor (or even a refund) for eligible Canadian dividends. That's because the company has already paid tax on those dividends. In contrast, holding U.S. or any foreign stock that yields dividends in a TFSA will pay 15% withholding tax and it is not recoverable. Correct, but the 15% is a special rate for regular shares and you need to fill out a W8-BEN. Your broker will probably make sure you have every few years. But if you hold the same stock in a non-registered account, this 15% withholding tax can be used as a foreign tax credit? Is this true or not or what are the considerations? That's true but reduces your Canadian tax payable, it's not refundable, so you have to have some tax to subtract it from. Another consideration is foreign dividends are included 100% in income no mater what the character is. That means you pay tax at your highest rate always if not held in a tax sheltered account. Canadian dividends that are in a non-registered account will pay taxes, I presume and I don't know how much, but the amount can be used also as a tax credit or are unrecoverable? What happens in order to take into account taxes paid by the company is, I read also that if you don't want to pay withholding taxes from foreign > dividends you can hold your stock in a RRSP or RRIF? You don't have any withholding taxes from US entities to what they consider Canadian retirement accounts. So TFSAs and RESPs aren't covered. Note that it has to be a US fund like SPY or VTI that trades in the US, and the account has to be RRSP/RRIF. You can't buy a Canadian listed ETF that holds US stocks and get the same treatment. This is also only for the US, not foreign like Europe or Asia. Also something like VT (total world) in the US will have withholding taxes from foreign (Europe & Asia mostly) before the money gets to the US. You can't get that back. Just an honourable mention for the UK, there's no withholding taxes for anybody, and I hear it's on sale. But at some point, if I withdraw the money, who do I need to pay taxes, > U.S. or Canada? Canada.",
"title": ""
},
{
"docid": "401753",
"text": "Actually, share holder value is is better maximised by borrowing, and paying dividends is fairly irrelevant but a natural phase on a mature and stable company. Company finance is generally a balance between borrowing, and money raised from shares. It should be self evident with a little thought that if not now, then in the future, a company should be able to create earnings in excess of the cost of borrowing, or it's not a very valuable company to invest in! In fact what's the point of borrowing if the cost of the interest is greater than whatever wealth is being generated? The important thing about this is that money raised from shares is more expensive than borrowing. If a company doesn't pay dividends, and its share price goes up because of the increasing value of the business, and in your example the company is not borrowing more because of this, then the proportion of the value of the company that is based on the borrowing goes down. So, this means a higher and higher proportion of the finance of a company is provided by the more expensive share holders than the less expensive borrowing, and thus the company is actually providing LESS value to share holders than it might. Of course, if a company doesn't pay a dividend AND borrows more, this is not true, but that's not the scenario in your question, and generally mature companies with mature earnings may as well pay dividends as they aren't on a massive expansion drive in the same way. Now, this relative expense of share holders and borrowing is MORE true for a mature company with stable earnings, as they are less of a risk and can borrow at more favourable rates, AND such a company is LIKELY to be expanding less rapidly than a small new innovative company, so for both these reasons returning money to share holders and borrowing (or maintaining existing lending facilities) maintains a relatively more efficient financing ratio. Of course all this means that in theory, a company should be more efficient if it has no share holders at all and borrows ALL of the money it needs. Yes. In practise though, lenders aren't so keen on that scenario, they would rather have shareholders sharing the risk, and lending a less than 100% proportion of the total of a companies finance means they are much more likely to get their money back if things go horribly wrong. To take a small start up company by comparison, lenders will be leary of lending at all, and will certainly impose high rates if they do, or ask for guarantors, or demand security (and security is only available if there is other investment besides the loan). So this is why a small start up is likely to be much more heavily or exclusively funded by share holders. Also the start up is likely not to pay a dividend, because for a start it's probably not making any profit, but even if it is and could pay a dividend, in this situation borrowing is unavailable or very expensive and this is a rapidly growing business that wants to keep its hands on all the cash it can to accelerate itself. Once it starts making money of course a start up is on its way to making the transition, it becomes able to borrow money at sensible rates, it becomes bigger and more valuable on the back of the borrowing. Another important point is that dividend income is more stable, at least for the mature companies with stable earnings of your scenario, and investors like stability. If all the income from a portfolio has to be generated by sales, what happens when there is a market crash? Suddenly the investor has to pay, where as with dividends, the company pays, at least for a while. If a company's earnings are hit by market conditions of course it's likely the dividend will eventually be cut, but short term volatility should be largely eliminated.",
"title": ""
},
{
"docid": "65295",
"text": "The owner of a long futures contract does not receive dividends, hence this is a disadvantage compared to owning the underlying stock. If the dividend is increased, and the future price would not change, there is an arbitrage possibility. For the sake of simplicity, assume that the stock suddenly starts paying a dividend, and that the risk free rate is zero (so interest does not play a role). One can expect that the future price is (rougly) equal to the stock price before the dividend announcment. If the future price would not change, an investor could buy the stock, and short a futures contract on the stock. At expiration he has to deliver the stock for the price set in the contract, which is under the assumptions here equal to the price he bought the stock for. But because he owned the stock, he receives the announced dividend. Hence he can make a risk-free profit consisting of the divivends. If interest do play a role, the argument is similar.",
"title": ""
},
{
"docid": "353337",
"text": "\"Whoa. These things are on two dimensions. It's like burger and fries, you can also have chicken sandwich and fries, or burger and onion rings. You can invest in an taxable brokerage account and/or an IRA. And then, within each of those... You can buy index funds and/or anything else. All 4 combinations are possible. If someone says otherwise, take your money and run. They are a shady financial \"\"advisor\"\" who is ripping you off by steering you only into products where they get a commission. Those products are more expensive because the commission comes out of your end. Not to mention any names. E.J. If you want financial advice that is honest, find a financial advisor who you pay for his advice, and who doesn't sell products at all. Or, just ask here. But I would start by listening to Suze Orman, Dave Ramsey, whomever you prefer. And read John Bogle's book. They can tell you all about the difference between money market, bonds, stocks, managed mutual funds (ripoff!) and index funds. IRA accounts, Roth IRA accounts and taxable accounts are all brokerage accounts. Within them, you can buy any security you want, including index funds. The difference is taxation. Suppose you earn $1000 and choose to invest it however Later you withdraw it and it has grown to $3000. Investing in a taxable account, you pay normal income tax on the $1000. When you later withdraw the $3000, you pay a tax on $2000 of income. If you invested more than a year, it is taxed at a much lower \"\"capital gains\"\" tax rate. With a traditional IRA account, you pay zero taxes on the initial $1000. Later, when you take the money out, you pay normal income tax on the full $3000. If you withdrew it before age 59-1/2, you also pay a 10% penalty ($300). With a Roth IRA account, you pay normal income tax on the $1000. When you withdraw the $3000 later, you pay NOTHING in taxes. Provided you followed the rules. You can invest in almost anything inside these accounts: Money market funds. Terrible return. You won't keep up with the market. Bonds. Low return but usually quite safe. Individual stocks. Good luck. Managed mutual funds. You're paying some genius stock picker to select high performing stocks. He has a huge staff of researchers and good social connections. He also charges you 1.5% per year overhead as an \"\"expense ratio\"\", which is a total loss to you. The fact is, he can usually pick stocks better than a monkey throwing darts. But he's not 1.5% better! Index funds. These just shrug and buy every stock on the market. There's no huge staff or genius manager, just some intern making small adjustments every week. As such, the expense ratio is extremely small, like 0.1%. If any of these investments pay dividends, you must pay taxes on them when they're issued, if you're not in an IRA account. This problem gets fixed in ETF's. Index ETF's. These are index funds packaged to behave like stocks. Dividends increase your stock's value instead of being paid out to you, which simplifies your taxes. If you buy index funds outside of an IRA, use these. Too many other options to get into here.\"",
"title": ""
},
{
"docid": "529996",
"text": "This is a great question for understanding how futures work, first let's start with your assumptions The most interesting thing here is that neither of these things really matters for the price of the futures. This may seem odd as a futures contract sounds like you are betting on the future price of the index, but remember that the current price already includes the expectations of future earnings as well! There is actually a fairly simple formula for the price of a futures contract (note the link is for forward contracts which are very similar but slightly more simple to understand). Note, that if you are given the current price of the underlying the futures price depends essentially only on the interest rate and the dividends paid during the length of the futures contract. In this case the dividend rate for the S&P500 is higher than the prevailing interest rate so the futures price is lower than the current price. It is slightly more complicated than this as you can see from the formula, but that is essentially how it works. Note, this is why people use futures contracts to mimic other exposures. As the price of the future moves (pretty much) in lockstep with the underlying and sometimes using futures to hedge exposures can be cheaper than buying etfs or using swaps. Edit: Example of the effect of dividends on futures prices For simplicity, let's imagine we are looking at a futures position on a stock that has only one dividend (D) in the near term and that this dividend happens to be scheduled for the day before the futures' delivery date. To make it even more simple lets say the price of the stock is fairly constant around a price P and interest rates are near zero. After the dividend, we would expect the price of the stock to be P' ~ P - D as if you buy the stock after the dividend you wouldn't get that dividend but you still expect to get the rest of the value from additional future cash flows of the company. However, if we buy the futures contract we will eventually own the stock but only after the dividend happens. Since we don't get that dividend cash that the owners of the stock will get we certainly wouldn't want to pay as much as we would pay for the stock (P). We should instead pay about P' the (expected) value of owning the stock after that date. So, in the end, we expect the stock price in the future (P') to be the futures' price today (P') and that should make us feel a lot more comfortable about what we our buying. Neither owning the stock or future is really necessarily favorable in the end you are just buying slightly different future expected cash flows and should expect to pay slightly different prices.",
"title": ""
},
{
"docid": "170318",
"text": "It depends on your investment profile but basically, dividends increase your taxable income. Anyone making an income will effectively get 'lower returns' on their investments due to this effect. If you had the choice between identical shares that either give a dividend or don't, you'll find that stock that pays a dividend has a lower price, and increases in value more slowly than stock that doesn't. (all other things being equal) There's a whole bunch of economic theory behind this but in short, the current stock price is a measure of how much the company is worth combined with an estimation of how much it will be worth in the future (NPV of all future dividends is the basic model). When the company makes profit, it can keep those profits, and invest in new projects or distribute a portion of those profits to shareholders (aka dividends). Distributing the value to shareholders reduces the value of the company somewhat, but the shareholders get the money now. If the company doesn't give dividends, it has a higher value which will be reflected in a higher stock price. So basically, all other things being equal (which they rarely are, but I digress) the price and growth difference reflects the fact that dividends are paying out now. (In other words, if you wanted non-dividend shares you could get them by buying dividend shares and re-investing the dividend as new shares every time there was a payout, and you could get dividend-share like properties by selling a percentage of non-dividend shares periodically). Dividend income is taxable as part of your income right away, however taxes on capital gains only happen when you sell the asset in question, and also has a lower tax rate. If you buy and hold Berkshire Hatheway, you will not have to pay taxes on the gains you get until you decide to sell the shares, and even then the tax rate will be lower. If you are investing for retirement, this is great, since your income from other sources will be lower, so you can afford to be taxed then. In many jurisdictions, income from capital gains is subject to a different tax rate than the rest of your income, for example in the US for most people with money to invest it's either 15% or 20%, which will be lower than normal income tax would be (since most people with money to invest would be making enough to be in a higher bracket). Say, for example, your income now is within the 25% bracket. Any dividend you get will be taxed at that rate, so let's say that the dividend is about 2% and the growth of the stock is about 4%. So, your effective growth rate after taxation is 5.5% -- you lose 0.5% from the 25% tax on the dividend. If, instead, you had stock with the same growth but no dividend it would grow at a rate of 6%. If you never withdrew the money, after 20 years, $1 in the dividend stock would be worth ~$2.92 (1.055^20), whereas $1 in the non-dividend stock would be worth ~$3.21 (1.06^20). You're talking about a difference of 30 cents per dollar invested, which doesn't seem huge but multiply it by 100,000 and you've got yourself enough money to renovate your house purely out of money that would have gone to the government instead. The advantage here is if you are saving up for retirement, when you retire you won't have much income so the tax on the gains (even ignoring the capital gains effect above) will definitely be less then when you were working, however if you had a dividend stock you would have been paying taxes on the dividend, at a higher rate, throughout the lifetime of the investment. So, there you go, that's what Mohnish Pabrai is talking about. There are some caveats to this. If the amount you are investing isn't large, and you are in a lower tax bracket, and the stock pays out relatively low dividends you won't really feel the difference much, even though it's there. Also, dividend vs. no dividend is hardly the highest priority when deciding what company to invest in, and you'll practically never be able to find identical companies that differ only on dividend/no dividend, so if you find a great buy you may not have a choice in the matter. Also, there has been a trend in recent years to also make capital gains tax progressive, so people who have a higher income will also pay more in capital gains, which negates part of the benefit of non-dividend stocks (but doesn't change the growth rate effects before the sale). There are also some theoretical arguments that dividend-paying companies should have stronger shareholders (since the company has less capital, it has to 'play nice' to get money either from new shares or from banks, which leads to less risky behavior) but it's not so cut-and-dried in real life.",
"title": ""
},
{
"docid": "511559",
"text": "\"While nothing is guaranteed - any stock market or country could collapse tomorrow - if you have a fairly long window (15+ years is certainly long), ETFs are likely to earn you well above inflation. Looking at long term ETFs, you typically see close to 10% annual growth over almost any ten year period in the US, and while I don't know European indexes, they're probably well above inflation at least. The downside of ETFs is that your money is somewhat less liquid than in a savings account, and any given year you might not earn anything - you easily could lose money in a particular year. As such, you shouldn't have money in ETFs that you expect to use in the next few months or year or even a few years, perhaps. But as long as you're willing to play the long game - ie, invest in ETF, don't touch it for 15 years except to reinvest the dividends - as long as you go with someone like Vanguard, and use a very low expense ratio fund (mine are 0.06% and 0.10%, I believe), you are likely in the long term to come out ahead. You can diversify your holdings - hold 10% to 20% in bond funds, for example - if you're concerned about risk; look at how some of the \"\"Target\"\" retirement funds allocate their investments to see how diversification can work [Target retirement funds assume high risk tolerance far out and then as the age grows the risk tolerance drops; don't invest in them, but it can be a good example of how to do it.] All of this does require a tolerance of risk, though, and you have to be able to not touch your funds even if they go down - studies have repeatedly shown that trying to time the market is a net loss for most people, and the best thing you can do when your (diverse) investments go down is stay neutral (talking about large funds here and not individual stocks). I think this answers 3 and 4. For 1, share price AND quantity matter (assuming no splits). This depends somewhat on the fund; but at minimum, funds must dividend to you what they receive as dividends. There are Dividend focused ETFs, which are an interesting topic in themselves; but a regular ETF doesn't usually have all that large of dividends. For more information, investopedia has an article on the subject. Note that there are also capital gains distributions, which are typically distributed to help offset capital gains taxes that may occur from time to time with an ETF. Those aren't really returns - you may have to hand most or all over to the IRS - so don't consider distributions the same way. The share price tracks the total net asset value of the fund divided by the number of shares (roughly, assuming no supply/demand split). This should go up as the stocks the ETF owns go up; overall, this is (for non-dividend ETFs) more often the larger volatility both up and down. For Vanguard's S&P500 ETF which you can see here, there were about $3.50 in dividends over 2014, which works out to about a 2% return ($185-$190 share price). On the other hand, the share price went from around $168 at the beginning of 2014 to $190 at the end of 2014, for a return of 13%. That was during a 'good' year for the market, of course; there will be years where you get 2-3% in dividends and lose money; in 2011 it opened at 116 and closed the year at 115 (I don't have the dividend for that year; certainly lower than 3.5% I'd think, but likely nonzero.) The one caveat here is that you do have stock splits, where they cut the price (say) in half and give you double the shares. That of course is revenue neutral - you have the same value the day after the split as before, net of market movements. All of this is good from a tax point of view, by the way; changes in price don't hit you until you sell the stock/fund (unless the fund has some capital gains), while dividends and distributions do. ETFs are seen as 'tax-friendly' for this reason. For 2, Vanguard is pretty good about this (in the US); I wouldn't necessarily invest monthly, but quarterly shouldn't be a problem. Just pay attention to the fees and figure out what the optimal frequency is (ie, assuming 10% return, what is your break even point). You would want to have some liquid assets anyway, so allow that liquid amount to rise over the quarter, then invest what you don't immediately see a need to use. You can see here Vanguard in the US has no fees for buying shares, but has a minimum of one share; so if you're buying their S&P500 (VOO), you'd need to wait until you had $200 or so to invest in order to invest additional funds.\"",
"title": ""
},
{
"docid": "163354",
"text": "Victor, Yes the drop in price does completely cancel the dividend at first. However, as others have noted, there are other forces working on the price as well. If dividends were pointless then the following scenario would be true: Let's assume, hypothetically, two identical stocks, only one of which pays a 2% annual dividend quarterly. At the end of the year we would expect the share price of the dividend stock to be 2% lower than the non-dividend stock. And an equal investment in both stocks would yield exactly the same amount of money. So that is a hypothetical, and here is real market example: I compared, i.e. took the ratio of Vanguard's S&P 500 ETF (VOO) closing price to the S&P 500 Index closing price from sep 9, (2010-2014), after accounting for the VOO 2013 split. The VOO pays a quarterly dividend(about 2%/year), the S&P is an index, hence no dividend. The VOO share price, reduced each quarter by the dividend, still grew more than the S&P each year except 2012 to 2013, but looking at the entire 4yr period the VOO share price grew 80.3987% while S&P grew 80.083% (1/3 of 1% more for VOO). VOO does drop about 1/2% relative to S&P on every ex date, but obviously it makes it up. There are other forces working on VOO. VOO is trade-able, therefore subject to supply/demand pressures, while the S&P 500 is not. So for the VOO ETF the data does not indicate pointless dividends but instead implies dividends are free money. StockCharts.com supports this. S&P500 for last 1244 days (9/8/2010) shows 90% growth http://stockcharts.com/freecharts/perf.php?%24SPX while VOO for last 1244 days shows 105% growth http://stockcharts.com/freecharts/perf.php?VOO",
"title": ""
},
{
"docid": "541718",
"text": "Leveraged ETFs are prone to volatility decay, also known as leverage decay: http://blog.quantumfading.com/2009/07/12/measuring-leveraged-etf-decay/ You can increase your chances by using a non-leveraged short ETF like TBF or simply shorting the long ETF. Beware: shorting bonds ETFs will result in you having the pay the dividends, which can be substantial. Edit: SBND has recently appeared on the market. It is leveraged 3x monthly. In theory, monthly leverage should be less destructive than daily leverage.",
"title": ""
},
{
"docid": "488015",
"text": "\"IMHO It is definitively not too early to start learning and thinking about personal finances and also about investing. If you like to try stock market games, make sure to use one that includes a realistic fee structure simulation as well - otherwise there'll be a very unpleasant awakening when switching to reality... I'd like to stress the need for low fees with the brokerage account! Sit down and calculate how much fees different brokers take for a \"\"portfolio\"\" of say, 1 ETF, 1 bond, 1 share of about $500 or $1000 each (e.g. order fee, annual fee, fee for paying out interest/dividend). In my experience, it is good if you can manage to make the first small investing steps before starting your career. Real jobs tend to need lots of time (particularly at the beginning), so time to learn investing is extremely scarce right at the time when you for the first time in your life earn money that could/should be invested. I'm talking of very slowly starting with a single purchase of say an ETF, a single bond next time you have saved up a suitable amount of toy money, then maybe a single share (and essentially not doing anything with them in order to avoid further fees). While such a \"\"portfolio\"\" is terrible with respect to diversification and relative fees*, this gives you the possibility to learn the procedures, to see how the fees cut in, what to do wrt taxes etc. This is why I speak about toy money and why I consider this money an investment in education. * An order fee of, say, $10 on a $500 position are terrible 4% (2 x $10) for buying + selling - depending on your local taxes, that would be several years of dividend yield for say some arbitrary Dow Jones ETF. Nevertheless, purchase + sale together are less than 3 cinema tickets.\"",
"title": ""
},
{
"docid": "244813",
"text": "\"It depends. Dividends and fees are usually unrelated. If the ETF holds a lot of stocks which pay significant dividends (e.g. an S&P500 index fund) these will probably cover the cost of the fees pretty readily. If the ETF holds a lot of stocks which do not pay significant dividends (e.g. growth stocks) there may not be any dividends - though hopefully there will be capital appreciation. Some ETFs don't contain stocks at all, but rather some other instruments (e.g. commodity-trust ETFs which hold precious metals like gold and silver, or daily-leveraged ETFs which hold options). In those cases there will never be any dividends. And depending on the performance of the market, the capital appreciation may or may not cover the expenses of the fund, either. If you look up QQQ's financials, you'll find it most recently paid out a dividend at an annualized rate of 0.71%. Its expense ratio is 0.20%. So the dividends more than cover its expense ratio. You could also ask \"\"why would I care?\"\" because unless you're doing some pretty-darned-specific tax-related modeling, it doesn't matter much whether the ETF covers its expense ratio via dividends or whether it comes out of capital gains. You should probably be more concerned with overall returns (for QQQ in the most recent year, 8.50% - which easily eclipses the dividends.)\"",
"title": ""
},
{
"docid": "354638",
"text": "\"This is an excellent question, one that I've pondered before as well. Here's how I've reconciled it in my mind. Why should we agree that a stock is worth anything? After all, if I purchase a share of said company, I own some small percentage of all of its assets, like land, capital equipment, accounts receivable, cash and securities holdings, etc., as others have pointed out. Notionally, that seems like it should be \"\"worth\"\" something. However, that doesn't give me the right to lay claim to them at will, as I'm just a (very small) minority shareholder. The old adage says that \"\"something is only worth what someone is willing to pay you for it.\"\" That share of stock doesn't actually give me any liquid control over the company's assets, so why should someone else be willing to pay me something for it? As you noted, one reason why a stock might be attractive to someone else is as a (potentially tax-advantaged) revenue stream via dividends. Especially in this low-interest-rate environment, this might well exceed that which I might obtain in the bond market. The payment of income to the investor is one way that a stock might have some \"\"inherent value\"\" that is attractive to investors. As you asked, though, what if the stock doesn't pay dividends? As a small shareholder, what's in it for me? Without any dividend payments, there's no regular method of receiving my invested capital back, so why should I, or anyone else, be willing to purchase the stock to begin with? I can think of a couple reasons: Expectation of a future dividend. You may believe that at some point in the future, the company will begin to pay a dividend to investors. Dividends are paid as a percentage of a company's total profits, so it may make sense to purchase the stock now, while there is no dividend, banking on growth during the no-dividend period that will result in even higher capital returns later. This kind of skirts your question: a non-dividend-paying stock might be worth something because it might turn into a dividend-paying stock in the future. Expectation of a future acquisition. This addresses the original premise of my argument above. If I can't, as a small shareholder, directly access the assets of the company, why should I attribute any value to that small piece of ownership? Because some other entity might be willing to pay me for it in the future. In the event of an acquisition, I will receive either cash or another company's shares in compensation, which often results in a capital gain for me as a shareholder. If I obtain a capital gain via cash as part of the deal, then this proves my point: the original, non-dividend-paying stock was worth something because some other entity decided to acquire the company, paying me more cash than I paid for my shares. They are willing to pay this price for the company because they can then reap its profits in the future. If I obtain a capital gain via stock in as part of the deal, then the process restarts in some sense. Maybe the new stock pays dividends. Otherwise, perhaps the new company will do something to make its stock worth more in the future, based on the same future expectations. The fact that ownership in a stock can hold such positive future expectations makes them \"\"worth something\"\" at any given time; if you purchase a stock and then want to sell it later, someone else is willing to purchase it from you so they can obtain the right to experience a positive capital return in the future. While stock valuation schemes will vary, both dividends and acquisition prices are related to a company's profits: This provides a connection between a company's profitability, expectations of future growth, and its stock price today, whether it currently pays dividends or not.\"",
"title": ""
},
{
"docid": "11032",
"text": "\"Let me provide a general answer, that might be helpful to others, without addressing those specific stocks. Dividends are simply corporate payouts made to the shareholders of the company. A company often decides to pay dividends because they have excess cash on hand and choose to return it to shareholders by quarterly payouts instead of stock buy backs or using the money to invest in new projects. I'm not exactly sure what you mean by \"\"dividend yield traps.\"\" If a company has declared an dividend for the upcoming quarter they will almost always pay. There are exceptions, like what happened with BP, but these exceptions are rare. Just because a company promises to pay a dividend in the approaching quarter does not mean that it will continue to pay a dividend in the future. If the company continues to pay a dividend in the future, it may be at a (significantly) different amount. Some companies are structured where nearly all of there corporate profits flow through to shareholders via dividends. These companies may have \"\"unusually\"\" high dividends, but this is simply a result of the corporate structure. Let me provide a quick example: Certain ETFs that track bonds pay a dividend as a way to pass through interest payments from the underlying bonds back to the shareholder of the ETF. There is no company that will continue to pay their dividend at the present rate with 100% certainty. Even large companies like General Electric slashed its dividend during the most recent financial crisis. So, to evaluate whether a company will keep paying a dividend you should look at the following: Update: In regards to one the first stock you mentioned, this sentence from the companies of Yahoo! finance explains the \"\"unusually\"\" dividend: The company has elected to be treated as a REIT for federal income tax purposes and would not be subject to income tax, if it distributes at least 90% of its REIT taxable income to its share holders.\"",
"title": ""
},
{
"docid": "566205",
"text": "\"I'm not a financial expert, but saying that paying a $1 dividend will reduce the value of the stock by $1 sounds like awfully simple-minded reasoning to me. It appears to be based on the assumption that the price of a stock is equal to the value of the assets of a company divided by the total number of shares. But that simply isn't true. You don't even need to do any in-depth analysis to prove it. Just look at share prices over a few days. You should easily be able to find stocks whose price varied wildly. If, say, a company becomes the target of a federal investigation, the share price will plummet the day the announcement is made. Did the company's assets really disappear that day? No. What's happened is that the company's long term prospects are now in doubt. Or a company announces a promising new product. The share price shoots up. They may not have sold a single unit of the new product yet, they haven't made a dollar. But their future prospects now look improved. Many factors go into determining a stock price. Sure, total assets is a factor. But more important is anticipated future earning. I think a very simple case could be made that if a stock never paid any dividends, and if everyone knew it would never pay any dividends, that stock is worthless. The stock will never produce any profit to the owner. So why should you be willing to pay anything for it? One could say, The value could go up and you could sell at a profit. But on what basis would the value go up? Why would investors be willing to pay larger and larger amounts of money for an asset that produces zero income? Update I think I understand the source of the confusion now, so let me add to my answer. Suppose that a company's stock is selling for, say, $10. And to simplify the discussion let's suppose that there is absolutely nothing affecting the value of that stock except an expected dividend. The company plans to pay a dividend on a specific date of $1 per share. This dividend is announced well in advance. Everyone knows that it will be paid, and everyone is extremely confidant that in fact the company really will pay it -- they won't run out of money or any such. Then in a pure market, we would expect that as the date of that dividend approaches, the price of the stock would rise until the day before the dividend is paid, it is $11. Then the day after the dividend is paid the price would fall back to $10. Why? Because the person who owns the stock on the \"\"dividend day\"\" will get that $1. So if you bought the stock the day before the dividend, the next day you would immediately receive $1. If without the dividend the stock is worth $10, then the day before the dividend the stock is worth $11 because you know that the next day you will get a $1 \"\"refund\"\". If you buy the stock the day after the dividend is paid, you will not get the $1 -- it will go to the person who had the stock yesterday -- so the value of the stock falls back to the \"\"normal\"\" $10. So if you look at the value of a stock immediately after a dividend is paid, yes, it will be less than it was the day before by an amount equal to the dividend. (Plus or minus all the other things that affect the value of a stock, which in many cases would totally mask this effect.) But this does not mean that the dividend is worthless. Just the opposite. The reason the stock price fell was precisely because the dividend has value. BUT IT ONLY HAS VALUE TO THE PERSON WHO GETS IT. It does me no good that YOU get a $1 dividend. I want ME to get the money. So if I buy the stock after the dividend was paid, I missed my chance. So sure, in the very short term, a stock loses value after paying a dividend. But this does not mean that dividends in general reduce the value of a stock. Just the opposite. The price fell because it had gone up in anticipation of the dividend and is now returning to the \"\"normal\"\" level. Without the dividend, the price would never have gone up in the first place. Imagine you had a company with negligible assets. For example, an accounting firm that rents office space so it doesn't own a building, its only tangible assets are some office supplies and the like. So if the company liquidates, it would be worth pretty much zero. Everybody knows that if liquidated, the company would be worth zero. Further suppose that everyone somehow knows that this company will never, ever again pay a dividend. (Maybe federal regulators are shutting the company down because it's products were declared unacceptably hazardous, or the company was built around one genius who just died, etc.) What is the stock worth? Zero. It is an investment that you KNOW has a zero return. Why would anyone be willing to pay anything for it? It's no answer to say that you might buy the stock in the hope that the price of the stock will go up and you can sell at a profit even with no dividends. Why would anyone else pay anything for this stock? Well, unless their stock certificates are pretty and people like to collect them or something like that. Otherwise you're supposing that people would knowingly buy into a pyramid scheme. (Of course in real life there are usually uncertainties. If a company is dying, some people may believe, rightly or wrongly, that there is still hope of reviving it. Etc.) Don't confuse the value of the assets of a company with the value of its stock. They are related, of course -- all else being equal, a company with a billion dollars in assets will have a higher market capitalization than a company with ten dollars in assets. But you can't calculate the price of a company's stock by adding up the value of all its assets, subtracting liabilities, and dividing by the number of shares. That's just not how it works. Long term, the value of any stock is not the value of the assets but the net present value of the total future expected dividends. Subject to all sorts of complexities in real life.\"",
"title": ""
},
{
"docid": "85977",
"text": "Chances are since college is your next likely step I would recommend saving up for it. Start building an emergency fund. Recommended $1,000 minimum. To start building your credit rating (when 18) get a low interest low limit credit. Pay off the balance every month. Starting to build your credit rating now can save you hundreds of thousands when buying a house over the course of paying it off. ie. cheaper interest rate. As for investing, the sooner you can get started the better. Acquire preferred/stocks/bonds/REITs/ETFs/etc that pay you to own them (they pay you dividends monthly/quarterly/etc). Stick with solid stocks that have a history of consistently increasing their dividends over time and that are solid companies. I personally follow the work/advice of Derek Foster. He's not a professional but he retired at 34. His first book (Stop working - Here's how you can) is great and recommend it to anyone who is looking to get started. Also check out Ramit Sethi's blog I Will Teach You to be Rich. He focuses on big wins which save you a lot over the long term. He's also got some great advice for students as well. Best of luck!",
"title": ""
},
{
"docid": "384607",
"text": "SPY does not reinvest dividends. From the SPY prospectus: No Dividend Reinvestment Service No dividend reinvestment service is provided by the Trust. Broker-dealers, at their own discretion, may offer a dividend reinvestment service under which additional Units are purchased in the secondary market at current market prices. SPY pays out quarterly the dividends it receives (after deducting fees and expenses). This is typical of ETFs. The SPY prospectus goes on to say: Distributions in cash that are reinvested in additional Units through a dividend reinvestment service, if offered by an investor’s broker-dealer, will be taxable dividends to the same extent as if such dividends had been received in cash.",
"title": ""
},
{
"docid": "532139",
"text": "The upvoted answers fail to note that dividends are the only benefit that investors collectively receive from the companies they invest in. If you purchase a share for $100, and then later sell it for $150, you should note that there is always someone that purchases the same share for $150. So, you get $150 immediately, but somebody else has to pay $150 immediately. So, investors collectively did not receive any money from the transaction. (Yes, share repurchase can be used instead of dividends, but it can be considered really another form of paying dividends.) The fair value of a stock is the discounted value of all future dividends the stock pays. It is so simple! This shows why dividends are important. Somebody might argue that many successful companies like Berkshire Hathaway do not pay dividend. Yes, it is true that they don't pay dividend now but they will eventually have to start paying dividend. If they reinvest potential dividends continuously, they will run out of things to invest in after several hundred years has passed. So, even in this case the value of the stock is still the discounted value of all future dividends. The only difference is that the dividends are not paid now; the companies will start to pay the dividends later when they run out of things to invest in. It is true that in theory a stock could pay an unsustainable amount of dividend that requires financing it with debt. This is obviously not a good solution. If you see a company that pays dividend while at the same time obtaining more cash from taking more debt or from share issues, think twice whether you want to invest in such a company. What you need to do to valuate companies fairly is to estimate the amount of dividend that can sustain the expected growth rate. It is typically about 60% of the earnings, because a part of the earnings needs to be invested in future growth, but the exact figure may vary depending on the company. Furthermore, to valuate a company, you need the expected growth rate of dividends and the discount rate. You simply discount all future dividends, correcting them up by the expected dividend growth rate and correcting them down by the discount rate.",
"title": ""
},
{
"docid": "393693",
"text": "For the Roth the earnings: interest, dividends, capital gains distributions and capital gains are tax deferred. Which means that as long as the money stays inside of a Roth or is transferred/rolled over to another Roth there are no taxes due. In December many mutual funds distribute their gains. Let's say people invested in S&P500index fund receive a dividend of 1% of their account value. The investor in a non-retirement fund will be paying tax on that dividend in the Spring with their tax form. The Roth and IRA investors will not be paying tax on those dividends. The Roth investor never will, and the regular IRA investor will only pay taxes on it when they pull the money out.",
"title": ""
},
{
"docid": "435125",
"text": "\"Most companies are taken over. One can reasonably guess that company X will be taken over for a price P, at some future point in time. Then the company has a value today, that is less than price P, by a large enough margin so that the investor will likely \"\"make out\"\" when the company finally is taken over at some unknown point in time. The exception is a company like Microsoft or Apple that basically grow too large to be taken over. But then they eventually start paying dividends when they become \"\"mature.\"\" Again, the trick, during the non-dividend paying period (e.g. ten or fifteen years ago) is to guess what dividends will be paid in some future time, and price the stock low enough today so that it will be worthwhile for the buyer.\"",
"title": ""
}
] |
688
|
Lamins have no effect on nuclear membrane structure maintenance.
|
[
{
"docid": "4452659",
"text": "Macroautophagy (hereafter referred to as autophagy) is a catabolic membrane trafficking process that degrades a variety of cellular constituents and is associated with human diseases. Although extensive studies have focused on autophagic turnover of cytoplasmic materials, little is known about the role of autophagy in degrading nuclear components. Here we report that the autophagy machinery mediates degradation of nuclear lamina components in mammals. The autophagy protein LC3/Atg8, which is involved in autophagy membrane trafficking and substrate delivery, is present in the nucleus and directly interacts with the nuclear lamina protein lamin B1, and binds to lamin-associated domains on chromatin. This LC3-lamin B1 interaction does not downregulate lamin B1 during starvation, but mediates its degradation upon oncogenic insults, such as by activated RAS. Lamin B1 degradation is achieved by nucleus-to-cytoplasm transport that delivers lamin B1 to the lysosome. Inhibiting autophagy or the LC3-lamin B1 interaction prevents activated RAS-induced lamin B1 loss and attenuates oncogene-induced senescence in primary human cells. Our study suggests that this new function of autophagy acts as a guarding mechanism protecting cells from tumorigenesis.",
"title": "Autophagy mediates degradation of nuclear lamina"
}
] |
[
{
"docid": "25036988",
"text": "Nuclear lamin B1 (LMNB1) constitutes one of the major structural proteins in the lamina mesh. We silenced the expression of LMNB1 by RNA interference in the colon cancer cell line DLD-1 and showed a dramatic redistribution of H3K27me3 from the periphery to a more homogeneous nuclear dispersion. In addition, we observed telomere attrition and an increased frequency of micronuclei and nuclear blebs. By 3D-FISH analyses, we demonstrated that the volume and surface of chromosome territories were significantly larger in LMNB1-depleted cells, suggesting that LMNB1 is required to maintain chromatin condensation in interphase nuclei. These changes led to a prolonged S phase due to activation of Chk1. Finally, silencing of LMNB1 resulted in extensive changes in alternative splicing of multiple genes and in a higher number of enlarged nuclear speckles. Taken together, our results suggest a mechanistic role of the nuclear lamina in the organization of chromosome territories, maintenance of genome integrity and proper gene splicing.",
"title": "Loss of lamin B1 results in prolongation of S phase and decondensation of chromosome territories."
},
{
"docid": "22544171",
"text": "Hutchinson-Gilford progeria syndrome (HGPS) is a childhood premature aging disease caused by a spontaneous point mutation in lamin A (encoded by LMNA), one of the major architectural elements of the mammalian cell nucleus. The HGPS mutation activates an aberrant cryptic splice site in LMNA pre-mRNA, leading to synthesis of a truncated lamin A protein and concomitant reduction in wild-type lamin A. Fibroblasts from individuals with HGPS have severe morphological abnormalities in nuclear envelope structure. Here we show that the cellular disease phenotype is reversible in cells from individuals with HGPS. Introduction of wild-type lamin A protein does not rescue the cellular disease symptoms. The mutant LMNA mRNA and lamin A protein can be efficiently eliminated by correction of the aberrant splicing event using a modified oligonucleotide targeted to the activated cryptic splice site. Upon splicing correction, HGPS fibroblasts assume normal nuclear morphology, the aberrant nuclear distribution and cellular levels of lamina-associated proteins are rescued, defects in heterochromatin-specific histone modifications are corrected and proper expression of several misregulated genes is reestablished. Our results establish proof of principle for the correction of the premature aging phenotype in individuals with HGPS.",
"title": "Reversal of the cellular phenotype in the premature aging disease Hutchinson-Gilford progeria syndrome"
},
{
"docid": "34747208",
"text": "Mutations in the nuclear structural protein lamin A cause the premature aging syndrome Hutchinson-Gilford progeria (HGPS). Whether lamin A plays any role in normal aging is unknown. We show that the same molecular mechanism responsible for HGPS is active in healthy cells. Cell nuclei from old individuals acquire defects similar to those of HGPS patient cells, including changes in histone modifications and increased DNA damage. Age-related nuclear defects are caused by sporadic use, in healthy individuals, of the same cryptic splice site in lamin A whose constitutive activation causes HGPS. Inhibition of this splice site reverses the nuclear defects associated with aging. These observations implicate lamin A in physiological aging.",
"title": "Lamin A-dependent nuclear defects in human aging."
},
{
"docid": "37362689",
"text": "The bulk of ATP consumed by various cellular processes in higher eukaryotes is normally produced by five multimeric protein complexes (I-V) embedded within the inner mitochondrial membrane, in a process known as oxidative phosphorylation (OXPHOS). Maintenance of energy homeostasis under most physiological conditions is therefore contingent upon the ability of OXPHOS to meet cellular changes in bioenergetic demand, with a chronic failure to do so being a frequent cause of human disease. With the exception of Complex II, the structural subunits of OXPHOS complexes are encoded by both the nuclear and the mitochondrial genomes. The physical separation of the two genomes necessitates that the expression of the 13 mitochondrially encoded polypeptides be co-ordinated with that of relevant nuclear-encoded partners in order to assemble functional holoenzyme complexes. Complex biogenesis is a highly ordered process, and several nuclear-encoded factors that function at distinct stages in the assembly of individual OXPHOS complexes have been identified.",
"title": "Oxidative phosphorylation: synthesis of mitochondrially encoded proteins and assembly of individual structural subunits into functional holoenzyme complexes."
},
{
"docid": "834336",
"text": "Hutchinson–Gilford progeria syndrome (HGPS; OMIM 176670) is an extremely rare but devastating disorder that mimics premature aging.1–3 Affected children appear normal at birth but typically develop failure to thrive in the first two years. Other features include alopecia, micrognathia, loss of subcutaneous fat with prominent veins, abnormal dentition, sclerodermatous skin changes, and osteolysis of the clavicles and distal phalanges. The mean age of death is at age 13 years, most commonly due to atherosclerosis. HGPS is mainly sporadic in occurrence, but a genetic cause has now been implicated following the identification of de novo heterozygous mutations in the LMNA gene in the majority of HGPS patients.4,5 A single family showing autosomal recessive inheritance of homozygous LMNA mutations has also been reported.6 LMNA encodes lamins A and C, components of the nuclear lamina, a meshwork underlying the nuclear envelope that serves as a structural support and is also thought to contribute to chromatin organisation and the regulation of gene expression.7,8 Interestingly, mutations in LMNA have recently been associated with at least eight inherited disorders, known as laminopathies, with differential dystrophic effects on a variety of tissues including muscle, neurones, skin, bone, and adipose tissue (reviewed in Mounkes et al 9). However, the realisation that these disorders share common genetic defects has led to clinical re-evaluation, with emerging evidence of significant phenotypic overlap.10 Hence the laminopathies might reasonably be considered as a spectrum of related diseases. HGPS has phenotypic similarities to several other laminopathies, in particular the atypical Werner’s syndrome11 and mandibuloacral dysplasia (MAD; OMIM 248370 and 608612).12 These diseases are associated with lipodystrophy,3,13 which is the most prominent feature of another laminopathy, familial partial lipodystrophy of the Dunnigan variety (OMIM 151660).14 MAD has been further classified as two …",
"title": "Compound heterozygous ZMPSTE24 mutations reduce prelamin A processing and result in a severe progeroid phenotype."
},
{
"docid": "7468449",
"text": "Ever since the first demonstration of their repetitive sequence and unique replication pathway, telomeres have beguiled researchers with how they function in protecting chromosome ends. Of course much has been learned over the years, and we now appreciate that telomeres are comprised of the multimeric protein/DNA shelterin complex and that the formation of t-loops provides protection from DNA damage machinery. Deriving their name from D-loops, t-loops are generated by the insertion of the 3' overhang into telomeric repeats facilitated by the binding of TRF2. Recent studies have uncovered novel forms of chromosome end-structure that may implicate telomere organization in cellular processes beyond its essential role in telomere protection and homeostasis. In particular, we have recently described that t-loops form in a TRF2-dependent manner at interstitial telomere repeat sequences, which we termed interstitial telomere loops (ITLs). These structures are also dependent on association of lamin A/C, a canonical component of the nucleoskeleton that is mutated in myriad human diseases, including human segmental progeroid syndromes. Since ITLs are associated with telomere stability and require functional lamin A/C, our study suggests a mechanistic link between cellular aging (replicative senescence induced by telomere shortening) and organismal aging (modeled by Hutchinson Gilford Progeria Syndrome). Here we speculate on other potential ramifications of ITL formation, from gene expression to genome stability to chromosome structure.",
"title": "A beginning of the end: new insights into the functional organization of telomeres"
},
{
"docid": "14446279",
"text": "In the yeast Saccharomyces cerevisiae that lacks lamins, the nuclear pore complex (NPC) has been proposed to serve a role in chromatin organization. Here, using fluorescence microscopy in living cells, we show that nuclear pore proteins of the Nup84 core complex, Nup84p, Nup145Cp, Nup120p, and Nup133p, serve to anchor telomere XI-L at the nuclear periphery. The integrity of this complex is shown to be required for repression of a URA3 gene inserted in the subtelomeric region of this chromosome end. Furthermore, altering the integrity of this complex decreases the efficiency of repair of a DNA double-strand break (DSB) only when it is generated in the subtelomeric region, even though the repair machinery is functional. These effects are specific to the Nup84 complex. Our observations thus confirm and extend the role played by the NPC, through the Nup84 complex, in the functional organization of chromatin. They also indicate that anchoring of telomeres is essential for efficient repair of DSBs occurring therein and is important for preserving genome integrity.",
"title": "Telomere tethering at the nuclear periphery is essential for efficient DNA double strand break repair in subtelomeric region"
},
{
"docid": "37608303",
"text": "Cristae, the organized invaginations of the mitochondrial inner membrane, respond structurally to the energetic demands of the cell. The mechanism by which these dynamic changes are regulated and the consequences thereof are largely unknown. Optic atrophy 1 (OPA1) is the mitochondrial GTPase responsible for inner membrane fusion and maintenance of cristae structure. Here, we report that OPA1 responds dynamically to changes in energetic conditions to regulate cristae structure. This cristae regulation is independent of OPA1's role in mitochondrial fusion, since an OPA1 mutant that can still oligomerize but has no fusion activity was able to maintain cristae structure. Importantly, OPA1 was required for resistance to starvation-induced cell death, for mitochondrial respiration, for growth in galactose media and for maintenance of ATP synthase assembly, independently of its fusion activity. We identified mitochondrial solute carriers (SLC25A) as OPA1 interactors and show that their pharmacological and genetic blockade inhibited OPA1 oligomerization and function. Thus, we propose a novel way in which OPA1 senses energy substrate availability, which modulates its function in the regulation of mitochondrial architecture in a SLC25A protein-dependent manner.",
"title": "OPA1-dependent cristae modulation is essential for cellular adaptation to metabolic demand."
},
{
"docid": "935034",
"text": "Publisher Summary The classification of cell death can be based on morphological or biochemical criteria or on the circumstances of its occurrence. Currently, irreversible structural alteration provides the only unequivocal evidence of death; biochemical indicators of cell death that are universally applicable have to be precisely defined and studies of cell function or of reproductive capacity do not necessarily differentiate between death and dormant states from which recovery may be possible. It has also proved feasible to categorize most if not all dying cells into one or the other of two discrete and distinctive patterns of morphological change, which have, generally, been found to occur under disparate but individually characteristic circumstances. One of these patterns is the swelling proceeding to rupture of plasma and organelle membranes and dissolution of organized structure—termed “coagulative necrosis. ” It results from injury by agents, such as toxins and ischemia, affects cells in groups rather than singly, and evokes exudative inflammation when it develops in vivo. The other morphological pattern is characterized by condensation of the cell with maintenance of organelle integrity and the formation of surface protuberances that separate as membrane-bounded globules; in tissues, these are phagocytosed and digested by resident cells, there being no associated inflammation.",
"title": "Cell death: the significance of apoptosis."
},
{
"docid": "4701662",
"text": "As phospholipids are synthesized mainly in the endoplasmic reticulum (ER) and mitochondrial inner membranes, how cells properly distribute specific phospholipids to diverse cellular membranes is a crucial problem for maintenance of organelle-specific phospholipid compositions. Although the ER-mitochondria encounter structure (ERMES) was proposed to facilitate phospholipid transfer between the ER and mitochondria, such a role of ERMES is still controversial and awaits experimental demonstration. Here we developed a novel in vitro assay system with isolated yeast membrane fractions to monitor phospholipid exchange between the ER and mitochondria. With this system, we found that phospholipid transport between the ER and mitochondria relies on membrane intactness, but not energy sources such as ATP, GTP or the membrane potential across the mitochondrial inner membrane. We further found that lack of the ERMES component impairs the phosphatidylserine transport from the ER to mitochondria, but not the phosphatidylethanolamine transport from mitochondria to the ER. This in vitro assay system thus offers a powerful tool to analyze the non-vesicular phospholipid transport between the ER and mitochondria.",
"title": "A phospholipid transfer function of ER-mitochondria encounter structure revealed in vitro"
},
{
"docid": "15692098",
"text": "Hutchinson-Gilford progeria syndrome (HGPS) is a rare but well known entity characterized by extreme short stature, low body weight, early loss of hair, lipodystrophy, scleroderma, decreased joint mobility, osteolysis, and facial features that resemble aged persons. Cardiovascular compromise leads to early demise. Cognitive development is normal. Data on 10 of our own cases and 132 cases from literature are presented. The incidence in the last century in the Netherlands was 1:4,000,000. Sex ratio was 1.2:1. Main first symptoms were failure to thrive (55%), hair loss (40%), skin problems (28%), and lipodystrophy (20%). Mean age at diagnosis was 2.9 years. Growth in weight was more disturbed than growth in height, and growth delay started already prenatally. Mean height > 13 years was 109.0 cm, mean weight was 14.5 kg. Osteolysis was wide-spread but not expressed, except in the viscerocranium, and remained limited to membranous formed bone. Lipodystrophy is generalized, only intra-abdominal fat depositions remain present. Cardiovascular problems are extremely variable, both in age of onset and nature. Stroke and coronary dysfunctioning are most frequent. Pathologic findings in coronaries and aorta resemble sometimes the findings in elderly persons, but can also be much more limited. Loss of smooth muscle cells seems the most important finding. Mean age of demise was 12.6 years. Patients can be subdivided in patients with classical HGPS, which follows an autosomal dominant pattern of inheritance, (almost) all cases representing spontaneous mutations, and in non-classical progeria, in whom growth can be less retarded, scalp hair remains present for a longer time, lipodystrophy is more slowly progressive, osteolysis is more expressed except in the face, and survival well into adulthood is not uncommon. Pattern of inheritance of non-classical progeria is most probably autosomal recessive. The cause of HGPS is an abnormally formed Lamin A, either directly by a mutated LMNA gene, or through abnormal posttranslational processing (ZMPSTE24 gene mutations). Of 34 LMNA mutations found in progeria patients, there were 26 classical p. G608G mutations (76%). Pathogenesis is most likely to follow several different pathways. Potential therapeutic strategies are developed along these lines and include RNA interference techniques and inhibition of the dominant-negative influence of abnormally formed Lamin A on polymerization with normally formed Lamin A.",
"title": "Hutchinson-Gilford progeria syndrome: review of the phenotype"
},
{
"docid": "8247597",
"text": "Mutations and deletions in the mitochondrial genome (mtDNA), as well as instability of the nuclear genome, are involved in multiple human diseases. Here, we report that in Saccharomyces cerevisiae, loss of mtDNA leads to nuclear genome instability, through a process of cell-cycle arrest and selection we define as a cellular crisis. This crisis is not mediated by the absence of respiration, but instead correlates with a reduction in the mitochondrial membrane potential. Analysis of cells undergoing this crisis identified a defect in iron-sulfur cluster (ISC) biogenesis, which requires normal mitochondrial function. We found that downregulation of nonmitochondrial ISC protein biogenesis was sufficient to cause increased genomic instability in cells with intact mitochondrial function. These results suggest mitochondrial dysfunction stimulates nuclear genome instability by inhibiting the production of ISC-containing protein(s), which are required for maintenance of nuclear genome integrity. For a video summary of this article, see the PaperFlick file available with the online Supplemental Data.",
"title": "Mitochondrial Dysfunction Leads to Nuclear Genome Instability via an Iron-Sulfur Cluster Defect"
},
{
"docid": "25787749",
"text": "The evolutionarily conserved G-quadruplexes (G4s) are faithfully inherited and serve a variety of cellular functions such as telomere maintenance, gene regulation, DNA replication initiation, and epigenetic regulation. Different from the Watson-Crick base-pairing found in duplex DNA, G4s are formed via Hoogsteen base pairing and are very stable and compact DNA structures. Failure of untangling them in the cell impedes DNA-based transactions and leads to genome instability. Cells have evolved highly specific helicases to resolve G4 structures. We used a recombinant nuclear form of Saccharomyces cerevisiae Pif1 to characterize Pif1-mediated DNA unwinding with a substrate mimicking an ongoing lagging strand synthesis stalled by G4s, which resembles a replication origin and a G4-structured flap in Okazaki fragment maturation. We find that the presence of G4 may greatly stimulate the Pif1 helicase to unwind duplex DNA. Further studies reveal that this stimulation results from G4-enhanced Pif1 dimerization, which is required for duplex DNA unwinding. This finding provides new insights into the properties and functions of G4s. We discuss the observed activation phenomenon in relation to the possible regulatory role of G4s in the rapid rescue of the stalled lagging strand synthesis by helping the replicator recognize and activate the replication origin as well as by quickly removing the G4-structured flap during Okazaki fragment maturation.",
"title": "G-quadruplexes significantly stimulate Pif1 helicase-catalyzed duplex DNA unwinding."
},
{
"docid": "30835854",
"text": "We have recently isolated SMAP (Smg GDS-associated protein; Smg GDS: small G protein GDP dissociation stimulator) as a novel Smg GDS-associated protein, which has Armadillo repeats and is phosphorylated by Src tyrosine kinase. SMAP is a human counterpart of mouse KAP3 (kinesin superfamily-associated protein) that is associated with mouse KIF3A/B (a kinesin superfamily protein), which functions as a microtubule-based ATPase motor for organelle transport. We isolated here a SMAP-interacting protein from a human brain cDNA library, identified it to be a human homolog of Xenopus XCAP-E (Xenopus chromosome-associated polypeptide), a subunit of condensins that regulate the assembly and structural maintenance of mitotic chromosomes, and named it HCAP (Human chromosome-associated polypeptide). Tissue and subcellular distribution analyses indicated that HCAP was ubiquitously expressed and highly concentrated in the nuclear fraction, where SMAP and KIF3B were also present. SMAP was extracted as a ternary complex with HCAP and KIF3B from the nuclear fraction in the presence of Mg-ATP. The results suggest that SMAP/KAP3 serves as a linker between HCAP and KIF3A/B in the nucleus, and that SMAP/KAP3 plays a role in the interaction of chromosomes with an ATPase motor protein.",
"title": "Complex formation of SMAP/KAP3, a KIF3A/B ATPase motor-associated protein, with a human chromosome-associated polypeptide."
},
{
"docid": "5914739",
"text": "The CD3ε and ζ cytoplasmic domains of the T cell receptor bind to the inner leaflet of the plasma membrane (PM), and a previous nuclear magnetic resonance structure showed that both tyrosines of the CD3ε immunoreceptor tyrosine-based activation motif partition into the bilayer. Electrostatic interactions between acidic phospholipids and clusters of basic CD3ε residues were previously shown to be essential for CD3ε and ζ membrane binding. Phosphatidylserine (PS) is the most abundant negatively charged lipid on the inner leaflet of the PM and makes a major contribution to membrane binding by the CD3ε cytoplasmic domain. Here, we show that TCR triggering by peptide--MHC complexes induces dissociation of the CD3ε cytoplasmic domain from the plasma membrane. Release of the CD3ε cytoplasmic domain from the membrane is accompanied by a substantial focal reduction in negative charge and available PS in TCR microclusters. These changes in the lipid composition of TCR microclusters even occur when TCR signaling is blocked with a Src kinase inhibitor. Local changes in the lipid composition of TCR microclusters thus render the CD3ε cytoplasmic domain accessible during early stages of T cell activation.",
"title": "Local changes in lipid environment of TCR microclusters regulate membrane binding by the CD3ε cytoplasmic domain"
},
{
"docid": "24770913",
"text": "Inwardly rectifying K+ channels (IRKs) are highly K(+)-selective, integral membrane proteins that help maintain resting the membrane potential and cell volume. Integral membrane proteins as a class are frequently N-glycosylated with the attached carbohydrate being extracellular and perhaps modulating function. However, dynamic effects of glycosylation have yet to be demonstrated at the molecular level. ROMK1, a member of the IRK family is particularly suited to the study of glycosylation because it has a single N-glycosylation consensus sequence (Ho, K., Nichols, C. G., Lederer, W. J., Lytton, J., Vassilev, P. M., Kanazirska, M. V., and Herbert, S. C. (1993) Nature 362, 31-38). We show that ROMK1 is expressed in a functional state in the plasmalemma of an insect cell line (Spodoptera frugiperda, Sf9) and has two structures, glycosylated and unglycosylated. To test functionality, glycosylation was abolished by an N117Q mutation or by treatment with tunicamycin. Whole cell currents were greatly reduced in both of the unglycosylated forms compared to wild-type. Single channel currents revealed a dramatic decrease in opening probability, po, as the causative factor. Thus we have shown biochemically that the N-glycosylation sequon is extracellular, a result consistent with present topological models of IRKs, and we conclude that sequon occupancy by carbohydrate stabilizes the open state of ROMK1.",
"title": "Potassium channel structure and function as reported by a single glycosylation sequon."
},
{
"docid": "43054703",
"text": "Neutrophil extracellular traps (NETs) are webs of DNA covered with antimicrobial molecules that constitute a newly described killing mechanism in innate immune defense. Previous publications reported that NETs take up to 3-4 h to form via an oxidant-dependent event that requires lytic death of neutrophils. In this study, we describe neutrophils responding uniquely to Staphylococcus aureus via a novel process of NET formation that did not require neutrophil lysis or even breach of the plasma membrane. The multilobular nucleus rapidly became rounded and condensed. During this process, we observed the separation of the inner and outer nuclear membranes and budding of vesicles, and the separated membranes and vesicles were filled with nuclear DNA. The vesicles were extruded intact into the extracellular space where they ruptured, and the chromatin was released. This entire process occurred via a unique, very rapid (5-60 min), oxidant-independent mechanism. Mitochondrial DNA constituted very little if any of these NETs. They did have a limited amount of proteolytic activity and were able to kill S. aureus. With time, the nuclear envelope ruptured, and DNA filled the cytoplasm presumably for later lytic NET production, but this was distinct from the vesicular release mechanism. Panton-Valentine leukocidin, autolysin, and a lipase were identified in supernatants with NET-inducing activity, but Panton-Valentine leukocidin was the dominant NET inducer. We describe a new mechanism of NET release that is very rapid and contributes to trapping and killing of S. aureus.",
"title": "A novel mechanism of rapid nuclear neutrophil extracellular trap formation in response to Staphylococcus aureus."
},
{
"docid": "14178995",
"text": "The genetic diseases Hutchinson-Gilford progeria syndrome (HGPS) and restrictive dermopathy (RD) arise from accumulation of farnesylated prelamin A because of defects in the lamin A maturation pathway. Both of these diseases exhibit symptoms that can be viewed as accelerated aging. The mechanism by which accumulation of farnesylated prelamin A leads to these accelerated aging phenotypes is not understood. Here we present evidence that in HGPS and RD fibroblasts, DNA damage checkpoints are persistently activated because of the compromise in genomic integrity. Inactivation of checkpoint kinases Ataxia-telangiectasia-mutated (ATM) and ATR (ATM- and Rad3-related) in these patient cells can partially overcome their early replication arrest. Treatment of patient cells with a protein farnesyltransferase inhibitor (FTI) did not result in reduction of DNA double-strand breaks and damage checkpoint signaling, although the treatment significantly reversed the aberrant shape of their nuclei. This suggests that DNA damage accumulation and aberrant nuclear morphology are independent phenotypes arising from prelamin A accumulation in these progeroid syndromes. Since DNA damage accumulation is an important contributor to the symptoms of HGPS, our results call into question the possibility of treatment of HGPS with FTIs alone.",
"title": "Summary"
},
{
"docid": "25483562",
"text": "Insulin-regulated aminopeptidase (IRAP or oxytocinase) is a membrane-bound zinc-metallopeptidase that cleaves neuroactive peptides in the brain and produces memory enhancing effects when inhibited. We have determined the crystal structure of human IRAP revealing a closed, four domain arrangement with a large, mostly buried cavity abutting the active site. The structure reveals that the GAMEN exopeptidase loop adopts a very different conformation from other aminopeptidases, thus explaining IRAP's unique specificity for cyclic peptides such as oxytocin and vasopressin. Computational docking of a series of IRAP-specific cognitive enhancers into the crystal structure provides a molecular basis for their structure-activity relationships and demonstrates that the structure will be a powerful tool in the development of new classes of cognitive enhancers for treating a variety of memory disorders such as Alzheimer's disease.",
"title": "Crystal structure of human insulin-regulated aminopeptidase with specificity for cyclic peptides."
},
{
"docid": "8883846",
"text": "The Global HIV Vaccine Enterprise convened a two-day workshop in May of 2007 to discuss humoral immune responses to HIV and approaches to design vaccines that induce viral neutralizing and other potentially protective antibody responses. The goals of this workshop were to identify key scientific issues, gaps, and opportunities that have emerged since the Enterprise Strategic Plan was first published in 2005 [1], and to make recommendations that Enterprise stakeholders can use to plan new activities. Most effective viral vaccines work, at least in part, by generating antibodies that inactivate or neutralize the invading virus, and the existing data strongly suggest that an optimally effective HIV-1 vaccine should elicit potent antiviral neutralizing antibodies. However, unlike acute viral pathogens, HIV-1 chronically replicates in the host and evades the antibody response. This immune evasion, along with the large genetic variation among HIV-1 strains worldwide, has posed major obstacles to vaccine development. Current HIV vaccine candidates do not elicit neutralizing antibodies against most circulating virus strains, and thus the induction of a protective antibody response remains a major priority for HIV-1 vaccine development. For an antibody-based HIV-1 vaccine, progress in vaccine design is generally gauged by in vitro assays that measure the ability of vaccine-induced antibodies to neutralize a broad spectrum of viral isolates representing the major genetic subtypes (clades) of HIV-1 [2]. Although it is not known what magnitude and breadth of neutralization will predict protection in vaccine recipients, it is clear that current vaccine immunogens elicit antibodies that neutralize only a minority of circulating isolates. Thus, much progress needs to be made in this area. Also, though virus neutralization is considered a critical benchmark for a vaccine, this may not be the only benchmark for predicting success with antibody-based HIV-1 vaccine immunogens. The main targets for neutralizing antibodies to HIV-1 are the surface gp120 and trans-membrane gp41 envelope glycoproteins (Env) that mediate receptor and coreceptor binding and the subsequent membrane fusion events that allow the virus to gain entry into cells [3]. Antibodies neutralize the virus by binding these viral spikes and blocking virus entry into susceptible cells, such as CD4+ T cells [4,5]. In order to chronically replicate in the host, the virus exploits several mechanisms to shield itself against antibody recognition, including a dense outer coating of sugar molecules (N-linked glycans) and the strategic positioning of cysteine–cysteine loop structures on the gp120 molecule [6–8]. These shielding mechanisms, although highly effective, have vulnerabilities imposed by fitness constraints. Information on the precise location and molecular structure of these vulnerable regions could be valuable for the rational design of improved vaccine immunogens. Participants in the workshop identified four areas that, if given proper attention, could provide key information that would bring the field closer to an effective antibody-based HIV-1 vaccine: (1) structure-assisted immunogen design, (2) role of Fc receptors and complement, (3) assay standardization and validation, and (4) immunoregulation of B cell responses.",
"title": "Antibody-Based HIV-1 Vaccines: Recent Developments and Future Directions"
},
{
"docid": "6969753",
"text": "Metastatic tumor cells that actively migrate and invade surrounding tissues rely on invadopodia to degrade extracellular matrix (ECM) barriers. Invadopodia are membrane protrusions that localize enzymes required for ECM degradation. Little is known about the formation, function, and regulation of invadopodia. Here, we show that invadopodia have two distinct aspects: (a) structural for organizing the cellular actin cytoskeleton to form membrane protrusions and (b) functional for using proteolytic enzyme(s) for ECM degradation. Small interfering RNA (siRNA) inhibition established that organization of invadopodia structure requires cortactin, whereas protease inhibitor studies identified membrane type 1 matrix metalloproteinase (MT1-MMP) as the key invadopodial enzyme responsible for gelatin matrix degradation in the breast carcinoma cell line MDA-MB-231. The inhibition of invadopodial structure assembly by cortactin depletion resulted in a block of matrix degradation due to failure of invadopodia formation. Either protease inhibition or MT1-MMP siRNA depletion moderately decreased the formation of invadopodial structures that were identified as actin-cortactin accumulations at the ventral cell membrane adherent to matrix. The invadopodia that were able to form upon MT1-MMP inhibition or depletion retained actin-cortactin accumulations but were unable to degrade matrix. Examination of cells at different time points as well as live-cell imaging revealed four distinct invadopodial stages: membrane cortactin aggregation at membranes adherent to matrix, MT1-MMP accumulation at the region of cortactin accumulation, matrix degradation at the invadopodia region, and subsequent cortactin dissociation from the area of continued MT1-MMP accumulation associated with foci of degraded matrix. Based on these results, we propose a stepwise model of invadopodia formation and function.",
"title": "Dynamic interactions of cortactin and membrane type 1 matrix metalloproteinase at invadopodia: defining the stages of invadopodia formation and function."
},
{
"docid": "37643601",
"text": "Many viruses go through a maturation step in the final stages of assembly before being transmitted to another host. The maturation process of flaviviruses is directed by the proteolytic cleavage of the precursor membrane protein (prM), turning inert virus into infectious particles. We have determined the 2.2 angstrom resolution crystal structure of a recombinant protein in which the dengue virus prM is linked to the envelope glycoprotein E. The structure represents the prM-E heterodimer and fits well into the cryo-electron microscopy density of immature virus at neutral pH. The pr peptide beta-barrel structure covers the fusion loop in E, preventing fusion with host cell membranes. The structure provides a basis for identifying the stages of its pH-directed conformational metamorphosis during maturation, ending with release of pr when budding from the host.",
"title": "The flavivirus precursor membrane-envelope protein complex: structure and maturation."
},
{
"docid": "35004872",
"text": "Asbestos has been described as a physical carcinogen in that its carcinogenic effects appear to be related primarily to fiber dimensions. It has been hypothesized that long asbestos fibers may interfere with chromosome distribution during cell division, causing genomic changes that lead to cell transformation and neoplastic progression. Using high-resolution time-lapse light microscopy and serial-section electron microscopy, we have followed individual crocidolite asbestos fibers through the later stages of cell division in LLC-MK2 epithelial cells, and have detailed for the first time their effect on cytokinesis. We found that long fibers (15-55 microgram), trapped by the cleavage furrow, sterically blocked cytokinesis, sometimes resulting in the formation of a binucleated cell. The ends of blocking fibers were usually found within invaginations of the newly formed nuclei. Nuclear envelope-fiber attachment was evident when a chromatin strand ran with the fiber into the intercellular bridge. Such strands may break, causing chromosome structural rearrangements. Our data are the first to show that individual crocidolite fibers can cause genomic changes by sterically blocking cytokinesis and that fiber length and affinity for the nuclear envelope are important factors. Such genomic changes may be among the initial events leading to asbestos-induced cancers.",
"title": "Long crocidolite asbestos fibers cause polyploidy by sterically blocking cytokinesis."
},
{
"docid": "7223604",
"text": "To study the effector function of the ADP- ribosylation factor (ARF) 6 GTP-binding protein, we transfected HeLa cells with wild-type, epitope-tagged ARF6. Previously shown to indirectly activate the ARF1 GTPase, aluminum fluoride (AIF) treatment of ARF6-transfected cells resulted in a redistribution of both ARF6 and actin to discrete sites on the plasma membrane, which became increasingly protrusive over time. The effects of AIF were reversible, specific to cells transfected with wild-type ARF6, and resembled the cellular protrusions observed in cells expressing the GTPase defective mutant of ARF6. Importantly, the protrusions observed in cells transfected with ARF6 were distinct from the enhanced stress fibers and membrane ruffles observed in cells transfected with RhoA and Rac1, respectively. In cells forming protrusions, there was an apparent stimulation of macropinocytosis and membrane recycling within the protrusive structures. In contrast, no block in transferrin uptake or alteration of the distribution of clathrin AP-2 complexes was detected in these cells. The AIF-induced, ARF6- dependent formation of protrusive structures was blocked by cytochalasin D and inhibitors of the lipoxygenase pathway. These observations support a novel role for the ARF6 GTPase in modeling the plasma membrane and underlying cytoskeleton.",
"title": "Aluminum fluoride stimulates surface protrusions in cells overexpressing the ARF6 GTPase"
},
{
"docid": "15414628",
"text": "Legionella pneumophila, the causative agent of Legionnaires' pneumonia, resides in a distinct vacuole structure called Legionella-containing vacuole (LCV). The LCV resists fusion with the lysosome and permits efficient bacterial replication in host macrophages, which requires a Dot/Icm type IVB secretion system. Dot/Icm-translocated effector SdhA is critical for L. pneumophila intracellular growth and functions to prevent host cell death. Here, we show that the absence of SdhA resulted in elevated caspase-1 activation and IL-1β secretion as well as macrophage pyroptosis during Legionella infection. These inflammasome activation phenotypes were independent of the established flagellin-NAIP5-NLRC4 axis, but relied on the DNA-sensing AIM2 inflammasome. We further demonstrate that Legionella DNA was released into macrophage cytosol, and this effect was significantly exaggerated by the absence of SdhA. SdhA bears a functional Golgi-targeting GRIP domain that is required for preventing AIM2 inflammasome activation. Ectopically expressed SdhA formed a unique ring-shape membrane structure, further indicating a role in membrane trafficking and maintaining LCV membrane integrity. Our data together suggest a possible link, mediated by the function of SdhA, between LCV trafficking/maturation and suppression of host innate immune detection.",
"title": "Preventing bacterial DNA release and absent in melanoma 2 inflammasome activation by a Legionella effector functioning in membrane trafficking."
},
{
"docid": "43752562",
"text": "Subcellular membranes of Saccharomyces cerevisiae, including mitochondria, microsomes, plasma membranes, secretory vesicles, vacuoles, nuclear membranes, peroxisomes, and lipid particles, were isolated by improved procedures and analyzed for their lipid composition and their capacity to synthesize phospholipids and to catalyze sterol delta 24-methylation. The microsomal fraction is heterogeneous in terms of density and classical microsomal marker proteins and also with respect to the distribution of phospholipid-synthesizing enzymes. The specific activity of phosphatidylserine synthase was highest in a microsomal subfraction which was distinct from heavier microsomes harboring phosphatidylinositol synthase and the phospholipid N-methyltransferases. The exclusive location of phosphatidylserine decarboxylase in mitochondria was confirmed. CDO-diacylglycerol synthase activity was found both in mitochondria and in microsomal membranes. Highest specific activities of glycerol-3-phosphate acyltransferase and sterol delta 24-methyltransferase were observed in the lipid particle fraction. Nuclear and plasma membranes, vacuoles, and peroxisomes contain only marginal activities of the lipid-synthesizing enzymes analyzed. The plasma membrane and secretory vesicles are enriched in ergosterol and in phosphatidylserine. Lipid particles are characterized by their high content of ergosteryl esters. The rigidity of the plasma membrane and of secretory vesicles, determined by measuring fluorescence anisotropy by using trimethylammonium diphenylhexatriene as a probe, can be attributed to the high content of ergosterol.",
"title": "Phospholipid synthesis and lipid composition of subcellular membranes in the unicellular eukaryote Saccharomyces cerevisiae."
},
{
"docid": "32827351",
"text": "Aqueous solutions of lead salts (1, 2) and saturated solutions of lead hydroxide (1) have been used as stains to enhance the electron-scattering properties of components of biological materials examined in the electron microscope. Saturated solutions of lead hydroxide (1), while staining more intensely than either lead acetate or monobasic lead acetate (l , 2), form insoluble lead carbonate upon exposure to air. The avoidance of such precipitates which contaminate surfaces of sections during staining has been the stimulus for the development of elaborate procedures for exclusion of air or carbon dioxide (3, 4). Several modifications of Watson's lead hydroxide stain (1) have recently appeared (5-7). All utilize relatively high pH (approximately 12) and one contains small amounts of tartrate (6), a relatively weak complexing agent (8), in addition to lead. These modified lead stains are less liable to contaminate the surface of the section with precipitated stain products. The stain reported here differs from previous alkaline lead stains in that the chelating agent, citrate, is in sufficient excess to sequester all lead present. Lead citrate, soluble in high concentrations in basic solutions, is a chelate compound with an apparent association constant (log Ka) between ligand and lead ion of 6.5 (9). Tissue binding sites, presumably organophosphates, and other anionic species present in biological components following fixation, dehydration, and plastic embedding apparently have a greater affinity for this cation than lead citrate inasmuch as cellular and extracellular structures in the section sequester lead from the staining solution. Alkaline lead citrate solutions are less likely to contaminate sections, as no precipitates form when droplets of fresh staining solution are exposed to air for periods of up to 30 minutes. The resultant staining of the sections is of high intensity in sections of Aralditeor Epon-embedded material. Cytoplasmic membranes, ribosomes, glycogen, and nuclear material are stained (Figs. 1 to 3). STAIN SOLUTION: Lead citrate is prepared by",
"title": "THE USE OF LEAD CITRATE AT HIGH pH AS AN ELECTRON-OPAQUE STAIN IN ELECTRON MICROSCOPY"
},
{
"docid": "12197393",
"text": "Cytochrome P450 (CYP) epoxygenases convert arachidonic acid to four epoxyeicosatrienoic acid (EET) regioisomers, 5,6-, 8,9-, 11,12-, and 14,15-EET, that function as autacrine and paracrine mediators. EETs produce vascular relaxation by activating smooth muscle large-conductance Ca2+-activated K+ channels (BKCa). In addition, they have anti-inflammatory effects on blood vessels and in the kidney, promote angiogenesis, and protect ischemic myocardium and brain. CYP epoxygenases also convert eicosapentaenoic acid to vasoactive epoxy-derivatives, and endocannabinoids containing 11,12- and 14,15-EET are formed. Many EET actions appear to be initiated by EET binding to a membrane receptor that activates ion channels and intracellular signal transduction pathways. However, EETs also are taken up by cells, are incorporated into phospholipids, and bind to cytosolic proteins and nuclear receptors, suggesting that some functions may occur through direct interaction of the EET with intracellular effector systems. Soluble epoxide hydrolase (sEH) converts EETs to dihydroxyeicosatrienoic acids (DHETs). Because this attenuates many of the functional effects of EETs, sEH inhibition is being evaluated as a mechanism for increasing and prolonging the beneficial actions of EETs.",
"title": "Arachidonic acid cytochrome P450 epoxygenase pathway."
},
{
"docid": "20743803",
"text": "The transmission of information in the brain depends on the highly polarized architecture of neurons. A number of cellular transport processes support this organization, including active targeting of proteins and passive corralling between compartments. The axon initial segment (AIS), which separates the somatodendritic and axonal compartments, has a key role in neuronal physiology, as both the initiation site of action potentials and the gatekeeper of the axonal arborization. Over the years, the AIS main components and their interactions have been progressively unraveled, as well as their role in the AIS assembly and maintenance. Two mechanisms have been shown to contribute to the regulation of protein transport at the AIS: a surface diffusion barrier and an intracellular traffic filter. However, a molecular understanding of these processes is still lacking. In the view of recent results on the AIS cytoskeleton structure, we will discuss how a better knowledge of the AIS architecture can help understanding its role in the regulation of protein transport and the maintenance of axonal identity.",
"title": "No Pasaran! Role of the axon initial segment in the regulation of protein transport and the maintenance of axonal identity."
},
{
"docid": "38300781",
"text": "Phospholipids are the major components of cell membranes, but they have functional roles beyond forming lipid bilayers. In particular, acidic phospholipids form microdomains in the plasma membrane and can ionically interact with proteins via polybasic sequences, which can have functional consequences for the protein. The list of proteins regulated by ionic protein-lipid interaction has been quickly expanding, and now includes membrane proteins, cytoplasmic soluble proteins, and viral proteins. Here we review how acidic phospholipids in the plasma membrane regulate protein structure and function via ionic interactions, and how Ca(2+) regulates ionic protein-lipid interactions via direct and indirect mechanisms.",
"title": "Ionic protein-lipid interaction at the plasma membrane: what can the charge do?"
}
] |
3029
|
What is the difference between hedging and diversification? How does each reduce risk?
|
[
{
"docid": "208977",
"text": "Hedging - You have an investment and are worried that the price might drop in the near future. You don't want to sell as this will realise a capital gain for which you may have to pay capital gains tax. So instead you make an investment in another instrument (sometimes called insurance) to offset falls in your investment. An example may be that you own shares in XYZ. You feel the price has risen sharply over the last month and is due for a steep fall. So you buy some put option over XYZ. You pay a small premium and if the price of XYZ falls you will lose money on the shares but will make money on the put option, thus limiting your losses. If the price continues to go up you will only lose the premium you paid for the option (very similar to an insurance policy). Diversification - This is when you may have say $100,000 to invest and spread your investments over a portfolio of shares, some units in a property fund and some bonds. So you are spreading your risks and returns over a range of products. The idea is if one stock or one sector goes down, you will not lose a large portion of your investment, as it is unlikely that all the different sectors will all go down at the same time.",
"title": ""
},
{
"docid": "314085",
"text": "\"The difference is in the interrelation between the varied investments you make. Hedging is about specifically offsetting a possible loss in an investment by making another related investment that will increase in value for the same reasons that the original investment would lose value. Gold, for instance, is often regarded as the ultimate hedge. Its value is typically inversely correlated to the rest of the market as a whole, because its status as a material, durable store of value makes it a preferred \"\"safe haven\"\" to move money into in times of economic downturn, when stock prices, bond yields and similar investments are losing value. That specific behavior makes investing in gold alongside stocks and bonds a \"\"hedge\"\"; the increase in value of gold as stock prices and bond yields fall limits losses in those other areas. Investment of cash in gold is also specifically a hedge against currency inflation; paper money, account balances, and even debt instruments like bonds and CDs can lose real value over time in a \"\"hot\"\" economy where there's more money than things to buy with it. By keeping a store of value in something other than currency, the price of that good will rise as the currencies used to buy it decrease in real value, maintaining your level of real wealth. Other hedges are more localized. One might, for example, trade oil futures as a hedge on a position in transportation stocks; when oil prices rise, trucking and airline companies suffer in the short term as their margins get squeezed due to fuel costs. Currency futures are another popular hedge; a company in international business will often trade options on the currencies of the companies it does business in, to limit the \"\"jitters\"\" seen in the FOREX spot market caused by speculation and other transient changes in market demand. Diversification, by contrast, is about choosing multiple unrelated investments, the idea being to limit losses due to a localized change in the market. Companies' stocks gain and lose value every day, and those companies can also go out of business without bringing the entire economy to its knees. By spreading your wealth among investments in multiple industries and companies of various sizes and global locations, you insulate yourself against the risk that any one of them will fail. If, tomorrow, Kroger grocery stores went bankrupt and shuttered all its stores, people in the regions it serves might be inconvenienced, but the market as a whole will move on. You, however, would have lost everything if you'd bet your retirement on that one stock. Nobody does that in the real world; instead, you put some of your money in Kroger, some in Microsoft, some in Home Depot, some in ALCOA, some in PG&E, etc etc. By investing in stocks that would be more or less unaffected by a downturn in another, if Kroger went bankrupt tomorrow you would still have, say, 95% of your investment next egg still alive, well and continuing to pay you dividends. The flip side is that if tomorrow, Kroger announced an exclusive deal with the Girl Scouts to sell their cookies, making them the only place in the country you can get them, you would miss out on the full possible amount of gains you'd get from the price spike if you had bet everything on Kroger. Hindsight's always 20/20; I could have spent some beer money to buy Bitcoins when they were changing hands for pennies apiece, and I'd be a multi-millionaire right now. You can't think that way when investing, because it's \"\"survivor bias\"\"; you see the successes topping the index charts, not the failures. You could just as easily have invested in any of the hundreds of Internet startups that don't last a year.\"",
"title": ""
}
] |
[
{
"docid": "134542",
"text": "\"When you invest in a single index/security, you are completely exposed to the risk of that security. Diversification means spreading the investments so the losses on one side can be compensated by the gains on the other side. What you are talking about is one thing called \"\"risk apettite\"\", more formally known as Risk Tolerance: Risk tolerance is the degree of variability in investment returns that an investor is willing to withstand. (emphasis added) This means that you are willing to accept some losses in order to get a potential bigger return. Fidelity has this graph: As you can see in the table above, the higher the risk tolerance, the bigger the difference between the best and worst values. That is the variability. The right-most pie can be one example of an agressive diversified portfolio. But this does not mean you should go and buy exactly that security compostion. High-risk means playing with fire. Unless you are a professional stuntman, playing with fire usually leaves people burnt. In a financial context this usually means the money is gone. Recommended Reading: Investopedia; Risk and Diversification: The Risk-Reward Tradeoff Investopedia; How to construct a High Risk portfolio Fidelity: Guide to Diversification KPMG: Understanding and articulating Risk Appetite (pdf)\"",
"title": ""
},
{
"docid": "519941",
"text": "\"The risk of any investment is measured by its incremental effect on the volatility of your overall personal wealth, including your other investments. The usual example is that adding a volatile stock to your portfolio may actually reduce the risk of your portfolio if it is negatively correlated with the other stuff in your portfolio. Common measures of risk, such as beta, assume that you have whole-market diversified portfolio. In the case of an investment that may or may not be hedged against currency movements, we can't say whether the hedge adds or removes risk for you without knowing what else is in your portfolio. If you are an EU citizen with nominally delimited savings or otherwise stand to lose buying power if the Euro depreciates relative to the dollar, than the \"\"hedged\"\" ETF is less risky than the \"\"unhedged\"\" version. On the other hand, if your background risk is such that you benefit from that depreciation, then the reverse is true. \"\"Hedging\"\" means reducing the risk already present in your portfolio. In this case it does not refer to reducing the individual volatility of the ETF. It may or may not do that but individual asset volatility and risk are two very different things.\"",
"title": ""
},
{
"docid": "186575",
"text": "You're missing the concept of systemic risk, which is the risk of the entire market or an entire asset class. Diversification is about achieving a balance between risk and return that's appropriate for you. Your investment in Vanguard's fund, although diversified between many public companies, is still restricted to one asset class in one country. Yes, you lower your risk by investing in all of these companies, but you don't erase it entirely. Clearly, there is still risk, despite your diversification. You may decide that you want other investments or a different asset allocation that reduce the overall risk of your portfolio. Over the long run, you may earn a high level of return, but never forget that there is still risk involved. bonds seem pretty worthless, at least until I retire According to your profile, you're about my age. Our cohort will probably begin retiring sometime around 2050 or later, and no one knows what the bond market will look like over the next 40 years. We may have forecasts for the next few years, but not for almost four decades. Writing off an entire asset class for almost four decades doesn't seem like a good idea. Also, bonds are like equity, and all other asset classes, in that there are different levels of risk within the asset class too. When calculating the overall risk/return profile of my portfolio, I certainly don't consider Treasuries as the same risk level as corporate bonds or high-yield (or junk) bonds from abroad. Depending on your risk preferences, you may find that an asset allocation that includes US and/or international bonds/fixed-income, international equities, real-estate, and cash (to make rebalancing your asset allocation easier) reduces your risk to levels you're willing to tolerate, while still allowing you to achieve returns during periods where one asset class, e.g. equities, is losing value or performing below your expectations.",
"title": ""
},
{
"docid": "43683",
"text": "If you have 100% of your money in one security that is inherently more risky than splitting your money 50/50 between two securities, regardless of the purported riskiness of the two securities. The calculations people use to justify their particular breed of diversification may carry some assumptions related risk/reward calculations. But these particular justifications don't change the fact that spreading your money across different assets protects your money from value variances of the individual assets. Splitting your $100 between Apple and Microsoft stock is probably less valuable (less well diversified) than splitting your money between Apple and Whole Foods stock but either way you're carrying less risk than putting all $100 in to Apple stock regardless of the assumed rates of return for any of these companies stock specifically. Edit: I'm sure the downvotes are because I didn't make a big deal about correlation and measuring correlation and standard deviations of returns and detailed portfolio theory. Measuring efficacy and justifying your particular allocations (that generally uses data from the past to project the future) is all well and good. Fact of the matter is, if you have 100% of your money in stock that's more stock risk than 25% in cash, 25% in bonds and 50% in stock would be because now you're in different asset classes. You can measure to your hearts delight the effects of splitting your money between different specific companies, or different industries, or different market capitalizations, or different countries or different fund managers or different whatever-metrics and doing any of those things will reduce your exposure to those specific allocations. It may be worth pointing out that currently the hot recommendation is a plain vanilla market tracking S&P 500 index fund (that just buys some of each of the 500 largest US companies without any consideration given to risk correlation) over standard deviation calculating actively managed funds. If you ask me that speaks volumes of the true efficacy of hyper analyzing the purported correlations of various securities.",
"title": ""
},
{
"docid": "331008",
"text": "\"I would like to first point out that there is nothing special about a self-managed investment portfolio as compared to one managed by someone else. With some exceptions, you can put together exactly the same investment portfolio yourself as a professional investor could put together for you. Not uncommonly, too, at a lower cost (and remember that cost is among the, if not the, best indicator(s) of how your investment portfolio will perform over time). Diversification is the concept of not \"\"putting all your eggs in one basket\"\". The idea here is that there are things that happen together because they have a common cause, and by spreading your investments in ways such that not all of your investments have the same underlying risks, you reduce your overall risk. The technical term for risk is generally volatility, meaning how much (in this case the price of) something fluctuates over a given period of time. A stock that falls 30% one month and then climbs 40% the next month is more volatile than one that falls 3% the first month and climbs 4% the second month. The former is riskier because if for some reason you need to sell when it is down, you lose a larger portion of your original investment with the former stock than with the latter. Diversification, thus, is reducing commonality between your investments, generally but not necessarily in an attempt to reduce the risk of all investments moving in the same direction by the same amount at the same time. You can diversify in various ways: Do you see where I am going with this? A well-diversed portfolio will tend to have a mix of equity in your own country and a variety of other countries, spread out over different types of equity (company stock, corporate bonds, government bonds, ...), in different sectors of the economy, in countries with differing growth patterns. It may contain uncommon classes of investments such as precious metals. A poorly diversified portfolio will likely be restricted to either some particular geographical area, type of equity or investment, focus on some particular sector of the economy (such as medicine or vehicle manufacturers), or so on. The poorly diversified portfolio can do better in the short term, if you time it just right and happen to pick exactly the right thing to buy or sell. This is incredibly hard to do, as you are basically working against everyone who gets paid to do that kind of work full time, plus computer-algorithm-based trading which is programmed to look for any exploitable patterns. It is virtually impossible to do for any real length of time. Thus, the well-diversified portfolio tends to do better over time.\"",
"title": ""
},
{
"docid": "144261",
"text": "\"Index funds are well-known to give the best long-term investment. Not exactly. Indexes give the best long term performance when compared to actively managing investments directly in the underlying stocks. That is, if you compare an S&P500 index to trying to pick stocks that are part of it, you're more likely to succeed with blindly following the index than trying to actively beat it. That said, no-one promises that investing in S&P500 is better than investing in DJIA, for example. These are two different indexes tracking different stocks and areas. So when advisers say \"\"diversify\"\" they don't mean it that you should diversify between different stocks that build up the S&P500 index. They mean that you should diversify your investments in different areas. Some in S&P500, some in DJIA, some in international indexes, some in bond indexes, etc. Still, investing in various indexes will likely yield better results than actively managing the investments trying to beat those indexes, but you should not invest in only one, and that is the meaning of diversification. In the comments you asked \"\"why diversify at all?\"\", and that is entirely a different question from your original \"\"what diversification is?\"\". You diversify to reduce the risk of loss from one side, and widen the net for gains from another. The thing is that any single investment can eventually fail, regardless of how it performed before. You can see that the S&P500 index lost 50% of its value twice within ten years, whereas before it was doubling itself every several years. Many people who were only invested in that index (or what's underlying to it) lost a lot of money. But consider you've diversified, and in the last 20 years you've invested in a blend of indexes that include the S&P500, but also other investments like S&P BSE SENSEX mentioned by Victor below. You would reduce your risk of loss on the American market by increasing your gains on the Indian market. Add to the mix soaring Chinese Real Estate market during the time of the collapse of the US real-estate, gains on the dollar losing its value by investing in other currencies (Canadian dollar, for example), etc. There are many risks, and by diversifying you mitigate them, and also have a chance to create other potential gains. Now, another question is why invest in indexes. That has been answered before on this site. It is my opinion that some methods of investing are just gambling by trying to catch the wave and they will almost always fail, and rarely will individual stock picking beat the market. Of course, after the fact its easy to be smart and pick the winning stocks. But the problem is to be able to predict those charts ahead of time.\"",
"title": ""
},
{
"docid": "30774",
"text": "The biggest challenge with owning any individual stock is price fluctuation, which is called risk. The scenarios you describe assume that the stock behaves exactly as you predict (price/portfolio doubles) and you need to consider risk. One way to measure risk in a stock or in a portfolio is Sharpe Ratio (risk adjusted return), or the related Sortino ratio. One piece of advice that is often offered to individual investors is to diversify, and the stated reason for diversification is to reduce risk. But that is not telling the whole story. When you are able to identify stocks that are not price correlated, you can construct a portfolio that reduces risk. You are trying to avoid 10% tax on the stock grant (25%-15%), but need to accept significant risk to avoid the 10% differential tax ($1000). An alternative to a single stock is to invest in an ETF (much lower risk), which you can buy and hold for a long time, and the price/growth of an ETF (ex. SPY) can be charted versus your stock to visualize the difference in growth/fluctuation. Look up the beta (volatility) of your stock compared to SPY (for example, IBM). Compare the beta of IBM and TSLA and note that you may accept higher volatility when you invest in a stock like Tesla over IBM. What is the beta of your stock? And how willing are you to accept that risk? When you can identify stocks that move in opposite directions, and mix your portfolio (look up beta balanced portolio), you can smooth out the variability (reduce the risk), although you may reduce your absolute return. This cannot be done with a single stock, but if you have more money to invest you could compose the rest of your portfolio to balance the risk for this stock grant, keep the grant shares, and still effectively manage risk. Some years ago I had accumulated over 10,000 shares (grants, options) in a company where I worked. During the time I worked there, their price varied between $30/share and < $1/share. I was able to liquidate at $3/share.",
"title": ""
},
{
"docid": "492506",
"text": "\"Taking examples from this loosely Googled page: http://www.fundlibrary.com/features/columns/page.asp?id=14406 If you find, or calculate, the standard deviation (volatility) of the returns from your various investment classes you will find they range from low-risk (low volatility), such as Cash, to high-risk (high volatility), such as Strategic Growth. The risk rating (volatility) is a good indicator of how reactive to market conditions your investment is likely to be. As you can see below, from mid-2010 to mid-2011 the High Risk index performed really well, but it was also most reactive when the market subsequently turned down. The medium risk indices performed the best over the chart period, 2010 to 2013, but it could have turned out different. Generally, you choose your investment according to your \"\"risk appetite\"\" - how much you're willing to risk. You might play safe with, say, 30% cash, 60% medium risk, 10% high risk. (Then again, are you paying someone to manage cash, which you might be able to do for free in a bank?) Assuming, for a moment, European (3.) and Intnl Equity Tracker (9.) had the same medium risk profile, then holding 50% & 50% would also add some currency diversification, which is usually advisable. However, the main choice is down to risk appetite. To address your specific question: \"\"my main interest for now is between Stockmarket Growth and Strategic Growth\"\", first thing to do is check their volatilities. For a further level of sophistication you can check how they are correlated against each other. If they are inversely correlated, i.e. one goes up when the other goes down, then holding some of each could be a good diversification. FYI: An Introduction to Investment Theory The historical returns are important too, but the investment classes your pension fund is offering will probably be reasonably aligned on a risk-return basis. You should check though. I.e. do they line up on a plot of 3 year Return vs Volatility? e.g. the line through SA Cash - SA Bonds - Vol Target 20 - SA Equity. Source\"",
"title": ""
},
{
"docid": "202432",
"text": "\"How do option market makers actually hedge their positions so that they do not have a price risk? You cannot complete hedge away price risk of a sold call simply by buying the underlying and waiting. As the price of the underlying decreases, the \"\"Delta\"\" (price risk) decreases, so as the underlying decreases, you would gradually sell some of the underlying to reduce your price risk from the underlying to match the price risk of the option. The opposite is true as well - as the price of the underlying increases, you'd buy more of the underlying to maintain a \"\"delta neutral\"\" position. If you want to employ this strategy, first you need to fully understand what \"\"delta\"\" is and how to calculate it. Then you can use delta hedging to reduce your price risk.\"",
"title": ""
},
{
"docid": "436904",
"text": "This is Ellie Lan, investment analyst at Betterment. To answer your question, American investors are drawn to use the S&P 500 (SPY) as a benchmark to measure the performance of Betterment portfolios, particularly because it’s familiar and it’s the index always reported in the news. However, going all in to invest in SPY is not a good investment strategy—and even using it to compare your own diversified investments is misleading. We outline some of the pitfalls of this approach in this article: Why the S&P 500 Is a Bad Benchmark. An “algo-advisor” service like Betterment is a preferable approach and provides a number of advantages over simply investing in ETFs (SPY or others like VOO or IVV) that track the S&P 500. So, why invest with Betterment rather than in the S&P 500? Let’s first look at the issue of diversification. SPY only exposes investors to stocks in the U.S. large cap market. This may feel acceptable because of home bias, which is the tendency to invest disproportionately in domestic equities relative to foreign equities, regardless of their home country. However, investing in one geography and one asset class is riskier than global diversification because inflation risk, exchange-rate risk, and interest-rate risk will likely affect all U.S. stocks to a similar degree in the event of a U.S. downturn. In contrast, a well-diversified portfolio invests in a balance between bonds and stocks, and the ratio of bonds to stocks is dependent upon the investment horizon as well as the individual's goals. By constructing a portfolio from stock and bond ETFs across the world, Betterment reduces your portfolio’s sensitivity to swings. And the diversification goes beyond mere asset class and geography. For example, Betterment’s basket of bond ETFs have varying durations (e.g., short-term Treasuries have an effective duration of less than six months vs. U.S. corporate bonds, which have an effective duration of just more than 8 years) and credit quality. The level of diversification further helps you manage risk. Dan Egan, Betterment’s Director of Behavioral Finance and Investing, examined the increase in returns by moving from a U.S.-only portfolio to a globally diversified portfolio. On a risk-adjusted basis, the Betterment portfolio has historically outperformed a simple DIY investor portfolio by as much as 1.8% per year, attributed solely to diversification. Now, let’s assume that the investor at hand (Investor A) is a sophisticated investor who understands the importance of diversification. Additionally, let’s assume that he understands the optimal allocation for his age, risk appetite, and investment horizon. Investor A will still benefit from investing with Betterment. Automating his portfolio management with Betterment helps to insulate Investor A from the ’behavior gap,’ or the tendency for investors to sacrifice returns due to bad timing. Studies show that individual investors lose, on average, anywhere between 1.2% to 4.3% due to the behavior gap, and this gap can be as high as 6.5% for the most active investors. Compared to the average investor, Betterment customers have a behavior gap that is 1.25% lower. How? Betterment has implemented smart design to discourage market timing and short-sighted decision making. For example, Betterment’s Tax Impact Preview feature allows users to view the tax hit of a withdrawal or allocation change before a decision is made. Currently, Betterment is the only automated investment service to offer this capability. This function allows you to see a detailed estimate of the expected gains or losses broken down by short- and long-term, making it possible for investors to make better decisions about whether short-term gains should be deferred to the long-term. Now, for the sake of comparison, let’s assume that we have an even more sophisticated investor (Investor B), who understands the pitfalls of the behavior gap and is somehow able to avoid it. Betterment is still a better tool for Investor B because it offers a suite of tax-efficient features, including tax loss harvesting, smarter cost-basis accounting, municipal bonds, smart dividend reinvesting, and more. Each of these strategies can be automatically deployed inside the portfolio—Investor B need not do a thing. Each of these strategies can boost returns by lowering tax exposure. To return to your initial question—why not simply invest in the S&P 500? Investing is a long-term proposition, particularly when saving for retirement or other goals with a time horizon of several decades. To be a successful long-term investor means employing the core principles of diversification, tax management, and behavior management. While the S&P might look like a ‘hot’ investment one year, there are always reversals of fortune. The goal with long-term passive investing—the kind of investing that Betterment offers—is to help you reach your investing goals as efficiently as possible. Lastly, Betterment offers best-in-industry advice about where to save and how much to save for no fee.",
"title": ""
},
{
"docid": "466950",
"text": "\"Having savings only in your home currency is relatively 'low risk' compared with other types of 'low diversification'. This is because, in a simple case, your future cash outflows will be in your home currency, so if the GBP fluctuates in value, it will (theoretically) still buy you the same goods at home. In this way, keeping your savings in the same currency as your future expenditures creates a natural hedge against currency fluctuation. This gets complicated for goods imported from other countries, where base price fluctuates based on a foreign currency, or for situations where you expect to incur significant foreign currency expenditures (retirement elsewhere, etc.). In such cases, you no longer have certainty that your future expenditures will be based on the GBP, and saving money in other currencies may make more sense. In many circumstances, 'diversification' of the currency of your savings may actually increase your risk, not decrease it. Be sure you are doing this for a specific reason, with a specific strategy, and not just to generally 'spread your money around'. Even in case of a Brexit, consider: what would you do with a bank account full of USD? If the answer is \"\"Convert it back to GBP when needed (in 6 months, 5 years, 30, etc.), to buy British goods\"\", then I wouldn't call this a way to reduce your risk. Instead, I would call it a type of investment, with its own set of risks associated.\"",
"title": ""
},
{
"docid": "124862",
"text": "\"To speak to this a little more broadly: apart from groups like hedge funds and other investors investing for purely speculative purposes, one of the major purposes of forwards (and, for that matter, futures) for companies in the \"\"real economy\"\" is to \"\"lock in\"\" a particular price in advance (or to reduce the risk of some kind of investment or transaction). Investopedia defines a currency forward as follows (with a few key points emphasized): [A currency forward is] a binding contract in the foreign exchange market that locks in the exchange rate for the purchase or sale of a currency on a future date. A currency forward is essentially a hedging tool that does not involve any upfront payment. The other major benefit of a currency forward is that it can be tailored to a particular amount and delivery period, unlike standardized currency futures. This can be a major advantage for planning and risk management purposes. For example, if I know I'm going to have to pay $1 million USD in the future and most of my revenue is in Euros, the actual amount I'll have to pay will vary based on the exchange rate between Euros and dollars. Thus, it's very worthwhile for me to be able to \"\"lock in\"\" a particular exchange rate so that I know exactly how much I'm going to pay relative to my projected revenue. The goal isn't necessarily to make money off the transaction (maybe they do, maybe they don't) as much as to reduce risk and improve planning ability. The fact that it doesn't involve an up-front payment is also a major advantage. It's usually a bad practice to \"\"sit on\"\" cash for a year if you can avoid it. Another key point: savings accounts pay less interest than inflation. If inflation is 3% and your savings account pays 1%, that looks remarkably like a guaranteed 2% loss to me.\"",
"title": ""
},
{
"docid": "496211",
"text": "A simple example - When looking at oil trading in different locations first I have some back of the envelop adjustments for the grade of oil, then look at storage costs (irrelevant in the case of electricity) and transport costs between two locations to see if physical players are actively arbing the spread. No strong views on reading material in this specific area - Google, google scholar and amazon all have relevant material. When it comes to your current problem, here are some questions to think about: 1. Is the power generated from the same commodity at location A and location W? 2. How has the spread changed in the past? Has trading location W actively hedged the worst cases of prices moves in location A? 3. Is it feasible to trade the commodity that location A generates the majority of its power from/how does that compare to electricity trading at location W as a hedge? 4. If hedging is really desirable, are you sure you can't do an illiquid over the counter hedge at location A? Paying a little bit more in the bid/ask for the hedge could be more desirable than trying to jump into a market you yourselves don't quite understand. 5. If your consultants come back with just some hedge ratios without discussing what drives the spreads between the two locations and where the spreads are currently be skeptical.",
"title": ""
},
{
"docid": "110729",
"text": "We face the same issue here in Switzerland. My background: Institutional investment management, currency risk management. My thoughs are: Home Bias is the core concept of your quesiton. You will find many research papers on this topic. The main problems with a high home bias is that the investment universe in your small local investment market is usually geared toward your coutries large corporations. Lack of diversification: In your case: the ASX top 4 are all financials, actually banks, making up almost 25% of the index. I would expect the bond market to be similarly concentrated but I dont know. In a portfolio context, this is certainly a negative. Liquidity: A smaller economy obviously has less large corporations when compared globally (check wikipedia / List_of_public_corporations_by_market_capitalization) thereby offering lower liquidity and a smaller investment universe. Currency Risk: I like your point on not taking a stance on FX. This simplifies the task to find a hedge ratio that minimises portfolio volatility when investing internationally and dealing with currencies. For equities, you would usually find that a hedge ratio anywhere from 0-30% is effective and for bonds one that ranges from 80-100%. The reason is that in an equity portfolio, currency risk contributes less to overall volatility than in a bond portfolio. Therefore you will need to hedge less to achieve the lowest possible risk. Interestingly, from a global perspective, we find, that the AUD is a special case whereby, if you hedge the AUD you actually increase total portfolio risk. Maybe it has to do with the AUD being used in carry trades a lot, but that is a wild guess. Hedged share classes: You could buy the currency hedged shared classes of investment funds to invest globally without taking currency risks. Be careful to read exactly what and how the share class implements its currency hedging though.",
"title": ""
},
{
"docid": "549306",
"text": "The word 'hedge' emerges from early agriculture when farmers would ask the market for a minimum buy price for each crop they planted. They used this method to stop loss against any major losses. Investors today use this strategy when they are unsure of what the market will do. A perfect hedge reduces your risk to nothing (except for the cost of the hedge).",
"title": ""
},
{
"docid": "477646",
"text": "\"Diversification is spreading your investments around so that one point of risk doesn't sink your whole portfolio. The effect of having a diversified portfolio is that you've always got something that's going up (though, the corollary is that you've also always got something going down... winning overall comes by picking investments worth investing in (not to state the obvious or anything :-) )) It's worth looking at the different types of risk you can mitigate with diversification: Company risk This is the risk that the company you bought actually sucks. For instance, you thought gold was going to go up, and so you bought a gold miner. Say there are only two -- ABC and XYZ. You buy XYZ. Then the CEO reveals their gold mine is played out, and the stock goes splat. You're wiped out. But gold does go up, and ABC does gangbusters, especially now they've got no competition. If you'd bought both XYZ and ABC, you would have diversified your company risk, and you would have been much better off. Say you invested $10K, $5K in each. XYZ goes to zero, and you lose that $5K. ABC goes up 120%, and is now worth $11K. So despite XYZ bankrupting, you're up 10% on your overall position. Sector risk You can categorize stocks by what \"\"sector\"\" they're in. We've already talked about one: gold miners. But there are many more, like utilities, bio-tech, transportation, banks, etc. Stocks in a sector will tend to move together, so you can be right about the company, but if the sector is out of favor, it's going to have a hard time going up. Lets extend the above example. What if you were wrong about gold going up? Then XYZ would still be bankrupt, and ABC would be making less money so they went down as well; say, 20%. At that point, you've only got $4K left. But say that besides gold, you also thought that banks were cheap. So, you split your investment between the gold miners and a couple of banks -- lets call them LMN and OP -- for $2500 each in XYZ, ABC, LMN, and OP. Say you were wrong about gold, but right about banks; LMN goes up 15%, and OP goes up 40%. At that point, your portfolio looks like this: XYZ start $2500 -100% end $0 ABC start $2500 +120% end $5500 LMN start $2500 +15% end $2875 OP start $2500 +40% end $3500 For a portfolio total of: $11,875, or a total gain of 18.75%. See how that works? Region/Country/Currency risk So, now what if everything's been going up in the USA, and everything seems so overpriced? Well, odds are, some area of the world is not over-bought. Like Brazil or England. So, you can buy some Brazilian or English companies, and diversify away from the USA. That way, if the market tanks here, those foreign companies aren't caught in it, and could still go up. This is the same idea as the sector risk, except it's location based, instead of business type based. There is an additional twist to this -- currencies. The Brits use the pound, and the Brazilians use the real. Most small investors don't think about this much, but the value of currencies, including our dollar, fluctuates. If the dollar has been strong, and the pound weak (as it has been, lately), then what happens if that changes? Say you own a British bank, and the dollar weakens and the pound strengthens. Even if that bank doesn't move at all, you would still make a gain. Example: You buy British bank BBB for 40 pounds a share, when each pound costs $1.20. Say after a while, BBB is still 40 pounds/share, but the dollar weakened and the pound strengthened, such that each pound is now worth $1.50. You could sell BBB, and because of the currency exchange once you've got it converted back to dollars you'd have a 25% gain. Market cap risk Sometimes big companies do well, sometimes it's small companies. The small caps are riskier but higher returning. When you think about it, small and mid cap stocks have much more \"\"room to run\"\" than large caps do. It's much easier to double a company worth $1 billion than it is to double a company worth $100 billion. Investment types Stocks aren't the only thing you can invest in. There's also bonds, convertible bonds, CDs, preferred stocks, options and futures. It can get pretty complicated, especially the last two. But each of these investment behaves differently; and again the idea is to have something going up all the time. The classical mix is stocks and bonds. The idea here is that when times are good, the stocks go up; when times are bad, the bonds go up (because they're safer, so more people want them), but mostly they're there to providing steady income and help keep your portfolio from cratering along with the stocks. Currently, this may not work out so well; stocks and bonds have been moving in sync for several years, and with interest rates so low they don't provide much income. So what does this mean to you? I'm going make some assumptions here based on your post. You said single index, self-managed, and don't lower overall risk (and return). I'm going to assume you're a small investor, young, you invest in ETFs, and the single index is the S&P 500 index ETF -- SPY. S&P 500 is, roughly, the 500 biggest companies in the USA. Further, it's weighted -- how much of each stock is in the index -- such that the bigger the company is, the bigger a percentage of the index it is. If slickcharts is right, the top 5 companies combined are already 11% of the index! (Apple, Microsoft, Exxon, Amazon, and Johnson & Johnson). The smallest, News Corp, is a measly 0.008% of the index. In other words, if all you're invested in is SPY, you're invested in a handfull of giant american companies, and a little bit of other stuff besides. To diversify: Company risk and sector risk aren't really relevant to you, since you want broad market ETFs; they've already got that covered. The first thing I would do is add some smaller companies -- get some ETFs for mid cap, and small cap value (not small cap growth; it sucks for structural reasons). Examples are IWR for mid-cap and VBR for small-cap value. After you've done that, and are comfortable with what you have, it may be time to branch out internationally. You can get ETFs for regions (such as the EU - check out IEV), or countries (like Japan - see EWJ). But you'd probably want to start with one that's \"\"all major countries that aren't the USA\"\" - check out EFA. In any case, don't go too crazy with it. As index investing goes, the S&P 500 is not a bad way to go. Feed in anything else a little bit at a time, and take the time to really understand what it is you're investing in. So for example, using the ETFs I mentioned, add in 10% each IWR and VBR. Then after you're comfortable, maybe add 10% EFA, and raise IWR to 20%. What the ultimate percentages are, of course, is something you have to decide for yourself. Or, you could just chuck it all and buy a single Target Date Retirement fund from, say, Vanguard or T. Rowe Price and just not worry about it.\"",
"title": ""
},
{
"docid": "591461",
"text": "\"I recommend you take a look at this lecture (really, the whole series is enlightening), from Swenson. He identifies 3 sources of returns: diversification, timing and selection. He appears to discard timing and selection as impossible. A student kinda calls him out on this. Diversification reduces risk, not increase returns. It turns out they did time the market, by shorting .com's before the bubble, and real estate just before the downturn. In 1990, Yale started a \"\"Absolute Return\"\" unit and allocated like 15 percent to it, mostly by selling US equities, that specializes in these sorts of hedging moves. As for why you might employ managers for specific areas, consider that the expense ratio Wall Street charges you or me still represent a very nice salary when applied to the billions in Yale's portfolio. So they hire internally to reduce expenses, and I'm sure they're kept busy. They also need people to sell off assets to maintain ratios, and figuring out which ones to sell might take specialized knowledge. Finally, in some areas, you functionally cannot invest without management. For example, Yale has a substantial allocation in private equity, and by definition that doesn't trade on the open market. The other thing you should consider is that for all its diversification, Yale lost 25 percent of their portfolio in 2009. For a technique that's supposed to reduce volatility, they seem to have a large range of returns over the past five years.\"",
"title": ""
},
{
"docid": "470587",
"text": "\"The optimal down payment is 100%. The only way you would do anything else when you have the cash to buy it outright is to invest the remaining money to get a better return. When you compare investments, you need to take risk into account as well. When you make loan payments, you are getting a risk free return. You can't find a risk-free investment that pays as much as your car loan will be. If you think you can \"\"game the system\"\" by taking a 0% loan, then you will end up paying more for the car, since the financing is baked into the sales [price in those cases (there is no such thing as free money). If you pay cash, you have much more bargaining power. Buy the car outright (negotiating as hard as you can), start saving what you would have been making as a car payment as an emergency fund, and you'll be ahead of the game. For the inflation hedge - you need to find investments that act as an inflation hedge - taking a loan does not \"\"hedge\"\" against inflation since you'll still be paying interest regardless of the inflation rate. The fact that you'll be paying slightly less interest (in \"\"real\"\" terms) does not make it a hedge. To answer the actual question, if your \"\"reinvestment rate\"\" (the return you can get from investing the \"\"borrowed\"\" cash) is less than the interest rate, then the more you put down, the greater your present value (PV). If your reinvestment rate is less than the interest rate, then the less you put down the better (not including risk). When you incorporate risk, though, the additional return is probably not worth the risk. So there is no \"\"optimal\"\" down payment in between those mathematically - it will depend on how much liquid cash you need (knowing that every dollar that you borrow is costing you interest).\"",
"title": ""
},
{
"docid": "102620",
"text": "You are diversified within a particular type of security. Notably the stock market. A truly diversified portfolio not only has multiple types of holdings within a single type of security (what your broad market fund does) but between different types. You have partially succeeded in doing this with the international fund - that way your risk is spread between domestic and international stocks. But there are other holdings. Cash, bonds, commodities, real estate, etc. There are broad index funds/ETFs for those as well, which may reduce your risk when the stock market as a whole tanks - which it does on occasion.",
"title": ""
},
{
"docid": "570787",
"text": "Basically, diversifying narrows the spread of possible results, raising the center of the returns bell-curve by reducing the likelihood of extreme results at either the high or low end. It's largely a matter of basic statistics. Bet double-or-nothing on a single coin flip, and those are the only possible results, and your odds of a disaster (losing most or all of the money) are 50%. Bet half of it on each of two coin flips, and your odds of losing are reduced to 25% at the cost of reducing your odds of winning to 25%, with 50% odds that you retain your money and can try the game again. Three coins divides the space further; the extremes are reduced to 12.5% each, with the middle being most likely. If that was all there was, this would be a zero-sum game and pure gambling. But the stock market is actually positive-sum, since companies are delivering part of their profits to their stockholder owners. This moves the center of the bell curve up a bit from break-even, historically to about +8%. This is why index funds produce a profit with very little active decision; they treat the variation as mostly random (which seems to work statistically) and just try to capture average results of a (hopefully) slightly above-average bucket of stocks and/or bonds. This approach is boring. It will never double your money overnight. On the other hand, it will never wipe you out overnight. If you have patience and are willing to let compound interest work for you, and trust that most market swings regress to the mean in the long run, it quietly builds your savings while not driving you crazy worrying about it. If all you are looking for is better return than the banks, and you have a reasonable amount of time before you need to pull the funds out, it's one of the more reliably predictable risk/reward trade-off points. You may want to refine this by biasing the mix of what you're holding. The simplest adjustment is how much you keep in each of several major investment categories. Large cap stocks, small cap stocks, bonds, and real estate (in the form of REITs) each have different baseline risk/return curves, and move in different ways in response to news, so maintaining a selected ratio between these buckets and adding the resulting curves together is one simple way to make fairly predictable adjustments to the width (and centerline) of the total bell curve. If you think you can do better than this, go for it. But index funds have been outperforming professionally managed funds (after the management fees are accounted for), and unless you are interested in spending a lot of time researching and playing with your money the odds of your doing much better aren't great unless you're willing to risk doing much worse. For me, boring is good. I want my savings to work for me rather than the other way around, and I don't consider the market at all interesting as a game. Others will feel differently.",
"title": ""
},
{
"docid": "409190",
"text": "\"Below I will try to explain two most common Binomial Option Pricing Models (BOPM) used. First of all, BOPM splits time to expiry into N equal sub-periods and assumes that in each period the underlying security price may rise or fall by a known proportion, so the value of an option in any sub-period is a function of its possible values in the following sub period. Therefore the current value of an option is found by working backwards from expiry date through sub-periods to current time. There is not enough information in the question from your textbook so we may assume that what you are asked to do is to find a value of a call option using just a Single Period BOPM. Here are two ways of doing this: First of all let's summarize your information: Current Share Price (Vs) = $70 Strike or exercise price (X) = $60 Risk-free rate (r) = 5.5% or 0.055 Time to maturity (t) = 12 months Downward movement in share price for the period (d) = $65 / $70 = 0.928571429 Upward movement in share price for the period (u) = 1/d = 1/0.928571429 = 1.076923077 \"\"u\"\" can be translated to $ multiplying by Vs => 1.076923077 * $70 = $75.38 which is the maximum probable share price in 12 months time. If you need more clarification here - the minimum and maximum future share prices are calculated from stocks past volatility which is a measure of risk. But because your textbook question does not seem to be asking this - you probably don't have to bother too much about it yet. Intrinsic Value: Just in case someone reading this is unclear - the Value of an option on maturity is the difference between the exercise (strike) price and the value of a share at the time of the option maturity. This is also called an intrinsic value. Note that American Option can be exercised prior to it's maturity in this case the intrinsic value it simply the diference between strike price and the underlying share price at the time of an exercise. But the Value of an option at period 0 (also called option price) is a price you would normally pay in order to buy it. So, say, with a strike of $60 and Share Price of $70 the intrinsic value is $10, whereas if Share Price was $50 the intrinsic value would be $0. The option price or the value of a call option in both cases would be fixed. So we also need to find intrinsic option values when price falls to the lowest probable and rises to the maximum probable (Vcd and Vcu respectively) (Vcd) = $65-$60 = $5 (remember if Strike was $70 then Vcd would be $0 because nobody would exercise an option that is out of the money) (Vcu) = $75.38-$60 = $15.38 1. Setting up a hedge ratio: h = Vs*(u-d)/(Vcu-Vcd) h = 70*(1.076923077-0.928571429)/(15.38-5) = 1 That means we have to write (sell) 1 option for each share purchased in order to hedge the risks. You can make a simple calculation to check this, but I'm not going to go into too much detail here as the equestion is not about hedging. Because this position is risk-free in equilibrium it should pay a risk-free rate (5.5%). Then, the formula to price an option (Vc) using the hedging approach is: (Vs-hVc)(e^(rt))=(Vsu-hVcu) Where (Vc) is the value of the call option, (h) is the hedge ratio, (Vs) - Current Share Price, (Vsu) - highest probable share price, (r) - risk-free rate, (t) - time in years, (Vcu) - value of a call option on maturity at the highest probable share price. Therefore solving for (Vc): (70-1*Vc)(e^(0.055*(12/12))) = (75.38-1*15.38) => (70-Vc)*1.056540615 = 60 => 70-Vc = 60/1.056540615 => Vc = 70 - (60/1.056540615) Which is similar to the formula given in your textbook, so I must assume that using 1+r would be simply a very close approximation of the formula above. Then it is easy to find that Vc = 13.2108911402 ~ $13.21 2. Risk-neutral valuation: Another way to calculate (Vc) is using a risk-neutral approach. We first introduce a variable (p) which is a risk-neutral probability of an increase in share price. p = (e^(r*t)-d)/(u-d) so in your case: p = (1.056540615-0.928571429)/(1.076923077-0.928571429) = 0.862607107 Therefore using (p) the (Vc) would be equal: Vc = [pVcu+(1-p)Vcd]/(e^(rt)) => Vc = [(0.862607107*15.38)+(0.137392893*5)]/1.056540615 => Vc = 13.2071229185 ~ $13.21 As you can see it is very close to the hedging approach. I hope this answers your questions. Also bear in mind that there is much more to the option pricing than this. The most important topics to cover are: Multi-period BOPM Accounting for Dividends Black-Scholes-Merton Option Pricing Model\"",
"title": ""
},
{
"docid": "322456",
"text": "\"No. This is too much for most individuals, even some small to medium businesses. When you sell that investment, and take the cheque into the foreign bank and wire it back to the USA in US dollars, you will definitely obtain the final value of the investment, converted to US$. Thats what you wanted, right? You'll get that. If you also hedge, unless you have a situation where it is a perfect hedge, then you are gambling on what the currencies will do. A perfect hedge is unusual for what most individuals are involved in. It looks something like this: you know ForeignCorp is going to pay you 10 million quatloos on Dec 31. So you go to a bank (probably a foreign bank, I've found they have lower limits for this kind of transaction and more customizable than what you might create trading futures contracts), and tell them, \"\"I have this contract for a 10 million quatloo receivable on Dec 31, I'd like to arrange a FX forward contract and lock in a rate for this in US$/quatloo.\"\" They may have a credit check or a deposit for such an arrangement, because as the rates change either the bank will owe you money or you will owe the bank money. If they quote you 0.05 US$/quatloo, then you know that when you hand the cheque over to the bank your contract payment will be worth US$500,000. The forward rate may differ from the current rate, thats how the bank accounts for risk and includes a profit. Even with a perfect hedge, you should be able to see the potential for trouble. If the bank doesnt quite trust you, and hey, banks arent known for trust, then as the quatloo strengthens relative to the US$, they may suspect that you will walk away from the deal. This risk can be reduced by including terms in the contract requiring you to pay the bank some quatloos as that happens. If the quatloo falls you would get this money credited back to your account. This is also how futures contracts work; there it is called \"\"mark to market accounting\"\". Trouble lurks here. Some people, seeing how they are down money on the hedge, cancel it. It is a classic mistake because it undoes the protection that one was trying to achieve. Often the rate will move back, and the hedger is left with less money than they would have had doing nothing, even though they bought a perfect hedge.\"",
"title": ""
},
{
"docid": "498378",
"text": "\"This depends strongly on what you mean by \"\"stock trading\"\". It isn't a single game, but a huge number of games grouped under a single name. You can invest in individual stocks. If you're willing to make the (large) effort needed to research the companies and their current position and potentialities, this can yield large returns at high risk, or moderate returns at moderate risk. You need to diversify across multiple stocks, and multiple kinds of stocks (and probably bonds and other investment vehicles as well) to manage that risk. Or you can invest in managed mutual funds, where someone picks and balances the stocks for you. They charge a fee for that service, which has to be subtracted from their stated returns. You need to decide how much you trust them. You will usually need to diversify across multiple funds to get the balance of risk you're looking for, with a few exceptions like Target Date funds. Or you can invest in index funds, which automate the stock-picking process to take a wide view of the market and count on the fact that, over time, the market as a whole moves upward. These may not produce the same returns on paper, but their fees are MUCH lower -- enough so that the actual returns to the investor can be as good as, or better than, managed funds. The same point about diversification remains true, with the same exceptions. Or you can invest in a mixture of these, plus bonds and other investment vehicles, to suit your own level of confidence in your abilities, confidence in the market as a whole, risk tolerance, and so on. Having said all that, there's also a huge difference between \"\"trading\"\" and \"\"investing\"\", at least as I use the terms. Stock trading on a short-term basis is much closer to pure gambling -- unless you do the work to deeply research the stocks in question so you know their value better than other people do, and you're playing against pros. You know the rule about poker: If you look around the table and don't see the sucker, he's sitting in your seat... well, that's true to some degree in short-term trading too. This isn't quite a zero-sum game, but it takes more work to play well than I consider worth the effort. Investing for the long term -- defining a balanced mixture of investments and maintaining that mixture for years, with purchases and sales chosen to keep things balanced -- is a positive sum game, since the market does drift upward over time at a long-term average of about 8%/year. If you're sufficiently diversified (which is one reason I like index funds), you're basically riding that rise. This puts you in the position of betting with the pros rather than against them, which is a lower-risk position. Of course the potential returns are reduced too, but I've found that \"\"market rate of return\"\" has been entirely adequate, though not exciting. Of course there's risk here too, if the market dips for some reason, such as the \"\"great recession\"\" we just went through -- but if you're planning for the long term you can usually ride out such dips, and perhaps even see them as opportunities to buy at a discount. Others can tell you more about the details of each of these, and may disagree with my characterizations ... but that's the approach I've taken, based on advice I trust. I could probably increase my returns if I was willing to invest more time and effort in doing so, but I don't especially like playing games for money, and I'm getting quite enough for my purposes and spending near-zero effort on it, which is exactly what I want.\"",
"title": ""
},
{
"docid": "436437",
"text": "The software you provided as an example won't teach you much about investing. The most important things of investing are: These are the only free lunches in investing. Allocation tells you how much expected return (and also how much risk) your portfolio has. Diversification is the only way to reduce risk without reducing return; however, just note that there is market risk that cannot be eliminated with diversification. Every penny you save on costs and taxes is important, as it's guaranteed return. If you were to develop e.g. software that calculates the expected return of a portfolio when given allocation as an input, it could teach you something about investing. Similarly, software that calculates the average costs of your mutual fund portfolio would teach you something about investing. But sadly, these kinds of software are uncommon.",
"title": ""
},
{
"docid": "286227",
"text": "diversifying; but isn't that what mutual funds already do? They diversify and reduce stock-specific risk by moving from individual stocks to many stocks, but you can diversify even further by selecting different fund types (e.g. large-cal, small-cap, fixed- income (bond) funds, international, etc.). Your target-date fund probably includes a few different types already, and will automatically reallocate to less risky investments as you get close to the target date. I would look at the fees of different types of funds, and compare them to the historical returns of those funds. You can also use things like morningstar and other ratings as guides, but they are generally very large buckets and may not be much help distinguishing between individual funds. So to answer the question, yes you can diversify further - and probably get better returns (and lower fees) that a target-date fund. The question is - is it worth your time and effort to do so? You're obviously comfortable investing for the long-term, so you might get some benefit by spending a little time looking for different funds to increase your diversification. Note that ETFs don't really diversify any differently than mutual funds, they are just a different mechanism to invest in funds, and allow different trading strategies (trading during the day, derivatives, selling short, etc.).",
"title": ""
},
{
"docid": "282376",
"text": "First of all, I think I'll clear off some confusion in the topic. The Sterling Ratio is a very simple investment portfolio measurement that fits nicely to the topic of personal finance, although not so much to a foreign exchange trading system. The Sterling Ratio is mainly used in the context of hedge funds to measure its risk-reward ratio for long term investments. To do so, it has been adapted to the following in order to appear more like the Sharpe Ratio: I Suppose this is why you question the Average Largest Draw-down. I'll come back to that later. It's original definition, suggested by the company Deane Sterling Jones, is a little different and perhaps the one you should use if you want to measure your trading system's long term risk-reward ratio, which is as followed: Note: Average Annual Draw-down has to be negative on the above-mentioned formula. This one is very simple to calculate and the one to use if you want to measure any portfolio's long-term results, such an example of a 5 or 10 years period and calculate the average of each years largest drawdown. To answer @Dheer's comment, this specific measurement can also be used in personal investments portfolio, which is considered a topic related to personal finance. Back to the first one, which answers your question. It's used in most cases in investment strategies, such as hedging, not trading systems. By hedging I mean that in these cases long term investments are made in anti-correlated securities to obtain a diversified portfolio with a very stable growth. This one is calculated normally annually because you rely on the Annual Risk-Free Rate. Having that in mind I think you can guess that the Average Largest Drawdown is the average between the Largest/Maximum Drawdown from each security in the portfolio. And this doesn't make sense in a trading system. Example: If you have invested in 5 different securities where we calculated the Largest Draw-down for each, such as represented in the following array: MaxDD[5] = { 0.12, 0.23, 0.06, 0.36, 0.09 }, in this case your Average Largest Draw-down is the average(MaxDD) that equals 0.172 or 17,2% If your portfolio's annual return is 15% and the Risk-free Rate is 10%, your Sterling Ratio SR = (0.15 - 0.10)/0.172, which result to 0.29. The higher the rate better is the risk-reward ratio of your portfolio. I suggest in your case to only use the original Sterling Ratio to calculate your long-term risk-reward, in any other case I suggest looking at the Sharpe and Sortino ratios instead.",
"title": ""
},
{
"docid": "323363",
"text": "In a word, no. Diversification is the first rule of investing. Your plan has poor diversification because it ignores most of the economy (large cap stocks). This means for the expected return your portfolio would get, you would bear an unnecessarily large amount of risk. Large cap and small cap stocks take turns outperforming each other. If you hold both, you have a safer portfolio because one will perform well while the other performs poorly. You will also likely want some exposure to the bond market. A simple and diversified portfolio would be a total market index fund and a total bond market fund. Something like 60% in the equity and 40% in the bonds would be reasonable. You may also want international exposure and maybe exposure to real estate via a REIT fund. You have expressed some risk-aversion in your post. The way to handle that is to take some of your money and keep it in your cash account and the rest into the diversified portfolio. Remember, when people add more and more asset classes (large cap, international, bonds, etc.) they are not increasing the risk of their portfolio, they are reducing it via diversification. The way to reduce it even more (after you have diversified) is to keep a larger proportion of it in a savings account or other guaranteed investment. BTW, your P2P lender investment seems like a great idea to me, but 60% of your money in it sounds like a lot.",
"title": ""
},
{
"docid": "259084",
"text": "Diversification is used by many to hopefully reduce the risk when bad investments are made. Diversification does not help you make more profits but instead averages down your profits. There is no way one can tell whether a stock or portfolio of stocks will go up or down once they are purchased. In order to try to provide some protection against total loss of the portfolio, a lazy so called long term investor will use diversification as a way of risk management. But the best outcome for them will be an averaging down of their profits. A better method is to let the market tell you when your purchased investment is a bad one and get out of that investment early and thus limiting your losses, whilst letting your good investments (as determined by the market) run and make larger profits.",
"title": ""
},
{
"docid": "365189",
"text": "At its simplest level it's an application of basic statistics/probability: Suppose you have n independent and identically distributed assets with the return on asset i denoted R_i which has mean m and variance s^2 (same for all assets). You can easily weaken these assumptions but I make them to simplify the exposition [Square brackets show a numerical example with n=20, m=8%, s=2%] if you invest in one of these assets you expect to get a return of m [8%] with standard deviation s [2%] (so you expect with probability 95% (approx) to get a return between m-2*s and m+2*s. [between 4% and 12%] Now suppose you split your money equally among the n-assets. Your return is now R = (1/n)\\Sum{i=1}^n R_i your expected return is E(R) = (1/n)\\Sum{i=1}^n E(R_i) = (1/n)\\Sum{i=1}^n m = m [8%] the variance of your return is Var(R) = Var( (1/n)\\Sum{i=1}^n R_i ) = (1/n^2)\\Sum{i=1}^n Var(R_i) = n * s^2 / n^2) = s^2/n So, the standard deviation is SD(R) = Sqrt(V(R)) = s/Sqrt(n) [2%/Sqrt(20) = 0.44%] Now, with 95% probability we get a return between E(R)-2*SD(R) and E(R)+2*SD(R) [between 7.12% and 8.88%]. This interval is smaller than when we invested in the single asset, so in effect with this portfolio we are achieving the same return m [8%] but with lower variance (risk) [0.44% instead of 2%]. This is the result of diversification. You can assume the assets are not independent (and most book expositions of this topic do indeed do that). In that case the calculation is modified because the variance of the portfolio now depends on the correlation between returns, as does the reduction in variance caused by the diversification. If assets are negatively correlated the result of the diversification will be more reduction in risk and vice versa. You can also assume the assets are not identically distributed and the above analysis does not change too much. You might look for some references on CAPM (Capital Asset Pricing Model) or portfolio theory but broadly these are based on what I have described above - finding the portfolio with minimum variance for a given return by investing proportionally in treasury bonds and risky assets.",
"title": ""
},
{
"docid": "160170",
"text": "What explains the most of the future returns of a portfolio is the allocation between asset classes. In the long term, stock investments are almost certain to return more than any other kinds of investments. For 40+ years, I would choose a portfolio of 100% stocks. How to construct the portfolio, then? Diversification is the key. You should diversify in time (don't put a large sum of money into your stock portfolio immediately; if you have a large sum to invest, spread it around several years). You should diversify based on company size (invest in both large and small companies). You should also diversify internationally (don't invest in just US companies). If you prefer to pick individual stocks, 20 very carefully selected stocks may provide enough diversification if you keep diversification in mind during stock picking. However, careful stock picking cannot be expected to yield excess returns, and if you pick stocks manually, you need to rebalance your portfolio occasionally. Thus, if you're lazy, I would recommend a mutual fund, or many mutual funds if you have difficulty finding a low-cost one that is internationally diversified. The most important consideration is the cost. You cannot expect careful fund selection to yield excess returns before expenses. However, the expenses are certain costs, so prefer low-cost funds. Almost always this means picking index funds. Avoid funds that have a small number of stocks, because they typically invest only in the largest companies, which means you fail to get diversification in company size. So, instead of Euro STOXX 50, select STOXX 600 when investing to the European market. ETFs may have lower costs than traditional mutual funds, so keep ETFs in mind when selecting the mutual funds in which to invest. For international diversification, do not forget emerging markets. It is not excessive to invest e.g. 20% to emerging markets. Emerging markets have a higher risk but they also have a higher return. A portfolio that does not include emerging markets is not in my opinion well diversified. When getting close to retirement age, I would consider increasing the percentage of bonds in the portfolio. This should be done primarily by putting additional money to bonds instead of selling existing investments to avoid additional taxes (not sure if this applies to other taxation systems than the Finnish one). Bond investments are best made though low-cost mutual funds as well. Keep bond investments in your local currency and risk-free assets (i.e. select US government bonds). Whatever you do, remember that historical return is no guarantee of future return. Actually, the opposite may be true: there is a mean reversion law. If a particular investment has returned well in the past, it often means its price has gone up, making it more likely that the price goes down in the future. So don't select a fund based on its historical return; instead, select a fund based on low costs. However, I'm 99% certain that over a period of 40 years, stocks will return better than other investments. In addition to fund costs, taxes are the other certain thing that will be deducted from your returns. Research what options you have to reduce the taxes you need to pay. 401-K was explained in another answer; this may be a good option. Some things recommended in other answers that I would avoid:",
"title": ""
}
] |
PLAIN-1241
|
garbanzo beans
|
[
{
"docid": "MED-3580",
"text": "The effects of the glycemic index (GI) of carbohydrate eaten the previous night on the glycemic response to a standard test meal eaten subsequently in the morning (breakfast) was studied. On separate evenings normal subjects ate low- or high-GI test meals of the same nutrient composition. The dinners consisted of single foods in two experiments and mixed meals containing several foods in the third. The differences between the observed glycemic responses to low- and high-GI dinners were predicted by their GIs. The glycemic responses to breakfast were significantly lower on mornings after low-GI dinners than after high-GI dinners. Eating, at dinner, foods with different fiber contents but the same GI had no effect on postbreakfast glycemia. We conclude that the GI predicts the difference between glycemic responses of mixed dinner meals; breakfast carbohydrate tolerance is improved when low-GI foods are eaten the previous evening.",
"title": "Second-meal effect: low-glycemic-index foods eaten at dinner improve subsequent breakfast glycemic response."
},
{
"docid": "MED-4347",
"text": "BACKGROUND: The nutritional composition of the dietary intake could produce specific effects on metabolic variables and inflammatory marker concentrations. This study assessed the effects of two hypocaloric diets (legume-restricted- vs. legume-based diet) on metabolic and inflammatory changes, accompanying weight loss. METHODS: Thirty obese subjects (17 M/13F; BMI: 32.5 ± 4.5 kg/m(2); 36 ± 8 years) were randomly assigned to one of the following hypocaloric treatments (8 weeks): Calorie-restricted legume-free diet (Control: C-diet) or calorie-restricted legume-based diet (L-diet), prescribing 4 weekly different cooked-servings (160-235 g) of lentils, chickpeas, peas or beans. Body composition, blood pressure (BP), blood biochemical and inflammatory marker concentrations as well as dietary intake were measured at baseline and after the nutritional intervention. RESULTS: The L-diet achieved a greater body weight loss, when compared to the C-diet (-7.8 ± 2.9% vs. -5.3 ± 2.7%; p = 0.024). Total and LDL cholesterol levels and systolic BP were improved only when consuming the L-diet (p < 0.05). L-diet also resulted in a significant higher reduction in C-reactive protein (CRP) and complement C3 (C3) concentrations (p < 0.05), compared to baseline and C-diet values. Interestingly, the reduction in the concentrations of CRP and C3 remained significantly higher to L-diet group, after adjusting by weight loss (p < 0.05). In addition, the reduction (%) in CRP concentrations was positively associated with decreases (%) in systolic BP and total cholesterol concentration specifically in the L-diet group, independent from weight loss (p < 0.05). CONCLUSION: The consumption of legumes (4 servings/week) within a hypocaloric diet resulted in a specific reduction in proinflammatory markers, such as CRP and C3 and a clinically significant improvement of some metabolic features (lipid profile and BP) in overweight/ obese subjects, which were in some cases independent from weight loss.",
"title": "A legume-based hypocaloric diet reduces proinflammatory status and improves metabolic features in overweight/obese subjects."
},
{
"docid": "MED-4509",
"text": "Hypercholesterolemia is a major modifiable risk factor for cardiovascular disease. Some, but not all, studies have shown that soy protein intake decreases total and low-density lipoprotein cholesterol and triglycerides and increases high-density lipoprotein cholesterol. The objective of this meta-analysis was to examine the effect of soy protein supplementation on serum lipid levels in adults. English language articles were retrieved by searching MEDLINE (1966 to February 2005) and the bibliographies of the retrieved articles. A total of 41 randomized controlled trials in which isolated soy protein supplementation was the only intervention and the net changes in serum lipids during intervention were reported. Information on study design, sample size, participant characteristics, intervention, follow-up duration, and treatment outcomes was independently abstracted using a standardized protocol. Using a random-effects model, data from each study were pooled and weighted by the inverse of their variance. Soy protein supplementation was associated with a significant reduction in mean serum total cholesterol (-5.26 mg/dl, 95% confidence interval [CI] -7.14 to -3.38), low-density lipoprotein cholesterol (-4.25 mg/dl, 95% CI -6.00 to -2.50), and triglycerides (-6.26 mg/dl, 95% CI -9.14 to -3.38) and a significant increase in high-density lipoprotein cholesterol (0.77 mg/dl, 95% CI 0.20 to 1.34). Meta-regression analyses showed a dose-response relation between soy protein and isoflavone supplementation and net changes in serum lipids. These results indicate that soy protein supplementation reduces serum lipids among adults with or without hypercholesterolemia. In conclusion, replacing foods high in saturated fat, trans-saturated fat, and cholesterol with soy protein may have a beneficial effect on coronary risk factors.",
"title": "A meta-analysis of the effect of soy protein supplementation on serum lipids."
},
{
"docid": "MED-4350",
"text": "Potatoes have the highest daily per capita consumption of all vegetables in the U.S. diet. Pigmented potatoes contain high concentrations of antioxidants, including phenolic acids, anthocyanins, and carotenoids. In a single-dose study six to eight microwaved potatoes with skins or a comparable amount of refined starch as cooked biscuits was given to eight normal fasting subjects; repeated samples of blood were taken over an 8 h period. Plasma antioxidant capacity was measured by ferric reducing antioxidant power (FRAP). A 24 h urine was taken before and after each regimen. Urine antioxidant capacity due to polyphenol was measured by Folin reagent after correction for nonphenolic interferences with a solid phase (Polyclar) procedure. Potato caused an increase in plasma and urine antioxidant capacity, whereas refined potato starch caused a decrease in both; that is, it acted as a pro-oxidant. In a crossover study 18 hypertensive subjects with an average BMI of 29 were given either six to eight small microwaved purple potatoes twice daily or no potatoes for 4 weeks and then given the other regimen for another 4 weeks. There was no significant effect of potato on fasting plasma glucose, lipids, or HbA1c. There was no significant body weight increase. Diastolic blood pressure significantly decreased 4.3%, a 4 mm reduction. Systolic blood pressure decreased 3.5%, a 5 mm reduction. This blood pressure drop occurred despite the fact that 14 of 18 subjects were taking antihypertensive drugs. This is the first study to investigate the effect of potatoes on blood pressure. Thus, purple potatoes are an effective hypotensive agent and lower the risk of heart disease and stroke in hypertensive subjects without weight gain.",
"title": "High-antioxidant potatoes: acute in vivo antioxidant source and hypotensive agent in humans after supplementation to hypertensive subjects."
},
{
"docid": "MED-4316",
"text": "The intestinal absorption of the essential trace element iron and its mobilization from storage sites in the body are controlled by systemic signals that reflect tissue iron requirements. Recent advances have indicated that the liver-derived peptide hepcidin plays a central role in this process by repressing iron release from intestinal enterocytes, macrophages and other body cells. When iron requirements are increased, hepcidin levels decline and more iron enters the plasma. It has been proposed that the level of circulating diferric transferrin, which reflects tissue iron levels, acts as a signal to alter hepcidin expression. In the liver, the proteins HFE, transferrin receptor 2 and hemojuvelin may be involved in mediating this signal as disruption of each of these molecules decreases hepcidin expression. Patients carrying mutations in these molecules or in hepcidin itself develop systemic iron loading (or hemochromatosis) due to their inability to down regulate iron absorption. Hepcidin is also responsible for the decreased plasma iron or hypoferremia that accompanies inflammation and various chronic diseases as its expression is stimulated by pro-inflammatory cytokines such as interleukin 6. The mechanisms underlying the regulation of hepcidin expression and how it acts on cells to control iron release are key areas of ongoing research. IUBMB Life, 57: 499-503, 2005.",
"title": "Systemic regulation of intestinal iron absorption."
},
{
"docid": "MED-4627",
"text": "The emerging role of chronic inflammation in the major degenerative diseases of modern society has stimulated research into the influence of nutrition and dietary patterns on inflammatory indices. Most human studies have correlated analyses of habitual dietary intake as determined by a food frequency questionnaire or 24-hour recall with systemic markers of inflammation like high-sensitivity C-reactive protein (HS-CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). An occasional study also includes nutrition analysis of blood components. There have been several controlled interventions which evaluated the effect of a change in dietary pattern or of single foods on inflammatory markers in defined populations. Most studies reveal a modest effect of dietary composition on some inflammatory markers in free-living adults, although different markers do not vary in unison. Significant dietary influences have been established for glycemic index (GI) and load (GL), fiber, fatty acid composition, magnesium, carotenoids, and flavonoids. A traditional Mediterranean dietary pattern, which typically has a high ratio of monounsaturated (MUFA) to saturated (SFA) fats and ω-3 to ω-6 polyunsaturated fatty acid (PUFAs) and supplies an abundance of fruits, vegetables, legumes, and grains, has shown anti-inflammatory effects when compared with typical North American and Northern European dietary patterns in most observational and interventional studies and may become the diet of choice for diminishing chronic inflammation in clinical practice.",
"title": "Diet and inflammation."
},
{
"docid": "MED-3582",
"text": "Breakfasts of lentils or wholemeal bread of identical carbohydrate content were taken by seven healthy volunteers. The lentils produced a significant 71% (p less than 0.001) reduction in the blood glucose area and flattened the plasma insulin and gastric inhibitory polypeptide responses by comparison with the bread. In addition, the lentil breakfast was followed by a significantly flatter blood glucose response to the standard bread lunch which followed 4 h later (by 38%, p less than 0.01). The blood glucose pattern was mimicked by feeding the bread breakfast slowly over the 4 h before lunch. Giving a bread breakfast containing a quarter of the carbohydrate reduced the breakfast glucose profile but resulted in a significantly impaired blood glucose response to lunch (168% of control, p less than 0.01). These results, together with breath hydrogen studies, performed on a separate group of four volunteers, indicate that the flattened response to lentils is not due to carbohydrate malabsorption. Slow release or \"lente\" carbohydrate foods such as lentils may form a useful part of the diets of those with impaired carbohydrate tolerance.",
"title": "Slow release dietary carbohydrate improves second meal tolerance."
},
{
"docid": "MED-3584",
"text": "Background: A high intake of white rice is associated with the metabolic syndrome and type 2 diabetes. Costa Ricans follow a staple dietary pattern that includes white rice and beans, yet the combined role of these foods on cardiometabolic risk factors has not been studied. Objective: We aimed to determine the association between intake of white rice and beans and the metabolic syndrome and its components in Costa Rican adults (n = 1879) without diabetes. Design: Multivariate-adjusted means were calculated for components of the metabolic syndrome by daily servings of white rice and beans (<1, 1, or >1) and by the ratio of beans to white rice. The OR for the metabolic syndrome was calculated by substituting one serving of beans for one serving of white rice. Results: An increase in daily servings of white rice was positively associated with systolic blood pressure (BP), triglycerides, and fasting glucose and inversely associated with HDL cholesterol (P-trend <0.01 for all). An increase in servings of beans was inversely associated with diastolic BP (P = 0.049). Significant trends for higher HDL cholesterol and lower BP and triglycerides were observed for 1:3, 1:2, 1:1, and 2:1 ratios of beans to white rice. Substituting one serving of beans for one serving of white rice was associated with a 35% (95% CI: 15%, 50%) lower risk of the metabolic syndrome. Conclusion: Increasing the ratio of beans to white rice, or limiting the intake of white rice by substituting beans, may lower cardiometabolic risk factors.",
"title": "A higher ratio of beans to white rice is associated with lower cardiometabolic risk factors in Costa Rican adults"
},
{
"docid": "MED-3581",
"text": "BACKGROUND: Low postprandial blood glucose is associated with low risk of metabolic diseases. A meal's ability to diminish the glucose response to carbohydrates eaten during the following meal is known as the \"second-meal effect\" (SME). The reduced glycemia elicited by low-glycemic-index (LGI) foods consumed during the first meal has been suggested as the main mechanism for SME. However, LGI foods often increase colonic fermentation because of the presence of fiber and resistant starch. OBJECTIVE: The objective was to study the SME of greater fermentation of high-glycemic-index (HGI) and LGI carbohydrates eaten during a previous meal. DESIGN: Ten healthy volunteers ate 3 breakfast test meals consisting of sponge cakes made with rapidly digestible, nonfermentable amylopectin starch plus cellulose (HGI meal), amylopectin starch plus the fermentable disaccharide lactulose (HGI-Lac meal), or slowly digestible, partly fermentable amylose starch plus cellulose (LGI meal). Five hours later, subjects were fed the same standard lunch containing 93 g available carbohydrates. Blood was collected for measurement of glucose, insulin, and nonesterified fatty acids (NEFAs). Breath hydrogen was measured as a marker of colonic fermentation. Postlunch gastric emptying was measured by using ultrasonography. RESULTS: Both the HGI-Lac and LGI meals improved glucose tolerance at lunch. In the case of the HGI-Lac meal, this effect was concomitant with low NEFA concentrations and delayed gastric emptying. CONCLUSION: Fermentable carbohydrates, independent of their effect on a food's glycemic index, have the potential to regulate postprandial responses to a second meal by reducing NEFA competition for glucose disposal and, to a minor extent, by affecting intestinal motility.",
"title": "Colonic fermentation of indigestible carbohydrates contributes to the second-meal effect."
},
{
"docid": "MED-4510",
"text": "Background and Aims Studies evaluating the effect of legume consumption on cholesterol have focused on soybeans, however non-soy legumes, such as a variety of beans, peas, and some seeds, are commonly consumed in Western countries. We conducted a meta-analysis of randomized controlled trials evaluating the effects of non-soy legume consumption on blood lipids. Methods and Results Studies were retrieved by searching MEDLINE (from January 1966 through July 2009), EMBASE (from January 1980 to July 2009), and the Cochrane Collaboration's Central Register of Controlled Clinical Trials using the following terms as medical subject headings and keywords: fabaceae not soybeans not isoflavones and diet or dietary fiber and cholesterol or hypercholesterolemia or triglycerides or cardiovascular diseases. Bibliographies of all retrieved articles were also searched. From 140 relevant reports, 10 randomized clinical trials were selected which compared a non-soy legume diet to control, had a minimum duration of 3 weeks, and reported blood lipid changes during intervention and control. Data on sample size, participant characteristics, study design, intervention methods, duration, and treatment results were independently abstracted by 2 investigators using a standardized protocol. Data from 10 trials representing 268 participants were examined using a random-effects model. Pooled mean net change in total cholesterol for those treated with a legume diet compared to control was −11.8 mg/dL (95% confidence interval [CI], −16.1 to −7.5); mean net change in low density lipoprotein cholesterol was −8.0 mg/dL (95% CI, −11.4 to −4.6). Conclusion These results indicate that a diet rich in legumes other than soy decreases total and LDL cholesterol.",
"title": "Non-Soy Legume Consumption Lowers Cholesterol Levels: A Meta-Analysis of Randomized Controlled Trials"
},
{
"docid": "MED-4318",
"text": "Preliminary data in the literature indicate that iron absorption from a meal may be increased when consumed with low-pH beverages such as cola, and it is also possible that sugar iron complexes may alter iron availability. A randomized, crossover trial was conducted to compare the bioavailability of nonheme iron from a vegetarian pizza meal when consumed with 3 different beverages (cola, diet cola, and mineral water). Sixteen women with serum ferritin concentrations of 11-54 µg/L were recruited and completed the study. The pizza meal contained native iron and added ferric chloride solution as a stable isotope extrinsic label; the total iron content of the meal was ~5.3 mg. Incorporation of iron from the meal into RBC was not affected by the type of drink (9.9% with cola, 9.4% with diet cola, and 9.6% with water). Serum ferritin and plasma hepcidin were correlated (r = 0.66; P<0.001) and both were significant predictors of iron bioavailability, but their combined effect explained only 30% of the inter-individual variation (P<0.001) and illustrates the current lack of understanding of mechanisms responsible for the fine-tuning of iron absorption. Although there was no effect of low-pH drinks on iron bioavailability in healthy women, their effect on absorption of fortification iron that requires solubilization in dilute acid, such as reduced iron, and in individuals with low gastric acid production, such as older people and individuals with Helicobacter pylori infection, warrants further investigation.",
"title": "Low-pH cola beverages do not affect women's iron absorption from a vegetarian meal."
},
{
"docid": "MED-4349",
"text": "Inflammation is a pathological condition underlying a number of diseases including cardiovascular diseases, cancer, and chronic inflammatory diseases. In addition, healthy, obese subjects also express markers of inflammation in their blood. Diet provides a variety of nutrients as well as non-nutritive bioactive constituents which modulate immunomodulatory and inflammatory processes. Epidemiological data suggest that dietary patterns strongly affect inflammatory processes. Primarily the intake of fruit and vegetables as well as of whole wheat is inversely associated with the risk of inflammation. In addition to observational studies there are also data from human intervention studies suggesting an anti-inflammatory potential of these plant foods. At the level of bioactive compounds occurring in plant foods, primarily carotenoids and flavonoids seem to modulate inflammatory as well as immunological processes. In conclusion, there is convincing evidence that plant foods and non-nutritive constituents associated with these foods modulate immunological and inflammatory processes. By means of anti-inflammatory activities a plant-based diet may contribute to the lower risk of cardiovascular diseases and cancer. A high intake of vegetables, fruit, and whole wheat as recommended by all international nutrition authorities provides a wide spectrum of bioactive compounds at health-promoting concentrations.",
"title": "Anti-inflammatory effects of plant-based foods and of their constituents."
},
{
"docid": "MED-4149",
"text": "Oxidative stress, i.e. excessive content of reactionary, oxygen, and nitrogen compounds (ROAC), including free radicals, is one of the causes of various dangerous diseases as well as premature aging. The adverse effect of free radicals can be neutralized by antioxidants. In order to carry out antioxidant therapy, one needs to know the contents of antioxidants in food products. We have created the databank for the contents of antioxidants in 1,140 food products, beverages, etc. Apart from water-soluble antioxidants, fat-soluble antioxidants in dairy and fish products, cacao, chocolate, nuts etc. were determined for the first time using an amperometric method.",
"title": "Creation of a databank for content of antioxidants in food products by an amperometric method."
},
{
"docid": "MED-4317",
"text": "Iron is an essential trace metal in human metabolism. However, imbalances in iron homeostasis are prevalent worldwide and have detrimental effects on human health. Humans do not have the ability to remove excess iron and therefore iron homeostasis is maintained by regulating the amount of iron entering the body from the diet. Iron is present in the human diet in number of different forms, including heme (from meat) and a variety of non-heme iron compounds. While heme is absorbed intact, the bioavailability of non-heme iron varies greatly depending on dietary composition. A number of dietary components are capable of interacting with iron to regulate its solubility and oxidation state. Interestingly, there is an emerging body of evidence suggesting that some nutrients also have direct effects on the expression and function of enterocyte iron transporters. In addition to dietary factors, body iron status is a major determinant of iron absorption. The roles of these important dietary and systemic factors in regulating iron absorption will be discussed in this review.",
"title": "Intestinal iron absorption: regulation by dietary & systemic factors."
},
{
"docid": "MED-3583",
"text": "Pulses are low-glycemic appetite-suppressing foods, but it is not known whether these properties persist after being consumed as part of a meal and after a second meal. The objective of this study was to determine the effects of a fixed-size pulse meal on appetite and blood glucose (BG) before and after an ad libitum test meal (pizza) and on food intake (FI) at the test meal. Males (n = 25; 21.3 ± 0.5 years; 21.6 ± 0.3 kg·m(-2)) randomly consumed 4 isocaloric meals: chickpea; lentil; yellow split pea; and macaroni and cheese (control). Commercially available canned pulses provided 250 kcal, and were consumed with macaroni and tomato sauce. FI was measured at a pizza meal 260 min after consumption of the isocaloric meal. BG and appetite were measured from 0 to 340 min. The lentil and yellow pea, but not chickpea, treatments led to lower appetite ratings during the 260 min prepizza meal period, and less FI at the pizza meal, compared with macaroni and cheese (p < 0.05). All pulse treatments lowered BG immediately following consumption (at 20 min) (p < 0.05), but there was no effect of treatment on prepizza meal BG AUC (p = 0.07). Immediately after the pizza meal, BG was lower following the chickpea and lentil treatments, but not the yellow pea treatment (p < 0.05). Postpizza meal BG AUC was lower following the chickpea and lentil treatments than in the yellow pea treatment (p < 0.05). The beneficial effects of consuming a pulse meal on appetite, FI at a later meal, and the BG response to a later meal are dependent on pulse type.",
"title": "First and second meal effects of pulses on blood glucose, appetite, and food intake at a later meal."
}
] |
[
{
"docid": "MED-2140",
"text": "Background Around the world, beans and rice are commonly consumed together as a meal. With type 2 diabetes increasing, the effect of this traditional diet pattern on glycemic response has not been studied fully. Methods We evaluated the glycemic response of bean and rice traditional meals compared to rice alone in adults with type 2 diabetes. Seventeen men and women with type 2 diabetes controlled by metformin (n = 14) or diet/exercise (n = 3) aged 35–70 years participated in the randomized 4 × 4 crossover trial. The white long grain rice control, pinto beans/rice, black beans/rice, red kidney beans/rice test meals, matched for 50 grams of available carbohydrate, were consumed at breakfast after a 12 hour fast. Capillary blood glucose concentrations at baseline and at 30 minute intervals up to 180 minutes postprandial were collected. MANOVA for repeated measures established glucose differences between treatments. Paired t tests identified differences between bean types and the rice control following a significant MANOVA. Results Postprandial net glucose values were significantly lower for the three bean/rice treatments in contrast to the rice control at 90, 120 and 150 minutes. Incremental area under the curve values were significantly lower for the pinto and black bean/rice meals compared to rice alone, but not for kidney beans. Conclusions Pinto, dark red kidney and black beans with rice attenuate the glycemic response compared to rice alone. Promotion of traditional foods may provide non-pharmaceutical management of type 2 diabetes and improve dietary adherence with cultural groups. Trial registration Clinical Trials number NCT01241253",
"title": "Bean and rice meals reduce postprandial glycemic response in adults with type 2 diabetes: a cross-over study"
},
{
"docid": "MED-4991",
"text": "BACKGROUND: Epidemiological studies have shown positive findings associated with legume consumption and measures of cardiovascular disease and obesity. However, few observational trials have examined beans as a separate food variable when determining associations with health parameters. OBJECTIVE: To determine the association of consuming beans on nutrient intakes and physiological parameters using the National Health and Examination Survey (NHANES) 1999-2002. METHODS: Using data from NHANES 1999-2002, a secondary analysis was completed with a reliable 24-hour dietary recall where three groups of bean consumers were identified (N = 1,475). We determined mean nutrient intakes and physiological values between bean consumers and non-consumers. Least square means, standard errors and ANOVA were calculated using appropriate sample weights following adjustment for age, gender, ethnicity and energy. RESULTS: Relative to non-consumers, bean consumers had higher intakes of dietary fiber, potassium, magnesium, iron, and copper (p's < 0.05). Those consuming beans had a lower body weight (p = 0.008) and a smaller waist size (p = 0.043) relative to non-consumers. Additionally, consumers of beans had a 23% reduced risk of increased waist size (p = 0.018) and a 22% reduced risk of being obese (p = 0.026). Also, baked bean consumption was associated with a lower systolic blood pressure. CONCLUSIONS: Bean consumers had better overall nutrient intake levels, better body weights and waist circumferences, and lower systolic blood pressure in comparison to non-consumers. These data support the benefits of bean consumption on improving nutrient intake and health parameters.",
"title": "Bean consumption is associated with greater nutrient intake, reduced systolic blood pressure, lower body weight, and a smaller waist circumference ..."
},
{
"docid": "MED-3138",
"text": "Background Many consumers avoid eating beans because they believe legume consumption will cause excessive intestinal gas or flatulence. An increasing body of research and the 2010 Dietary Guidelines for Americans supports the benefits of a plant-based diet, and legumes specifically, in the reduction of chronic disease risks. The purpose of the current research was to investigate the perception of increased flatulence and gastrointestinal discomfort among participants who consumed a ½ cup of beans daily for 8 or 12 weeks. Methods Participants in three studies to test the effects of beans on heart disease biomarkers completed the same weekly questionnaire to assess gastrointestinal discomfort issues such as increased flatulence, stool changes, and bloating. Studies 1 and 2 were randomized crossover trials. Participants consumed ½ cup of pinto beans, black-eyed peas, and canned carrots as control (n = 17) in Study 1 for three randomized 8-week phases. For Study 2, participants ate ½ cup baked beans or canned carrots as control (n = 29) for two randomized 8-week phases. Study 3 was a parallel arm trial with 40 subjects receiving ½ cup pinto beans and 40 consuming a control soup for 12 weeks. Changes in the frequency of perceived flatulence, stool characteristics, and bloating were the primary outcome measures. Chi-square distributions were examined for the presence or absence of symptoms and demographic characteristics to determine differences by gender, age, body mass index (BMI), and bean type. Results Less than 50% reported increased flatulence from eating pinto or baked beans during the first week of each trial, but only 19% had a flatulence increase with black-eyed peas. A small percentage (3-11%) reported increased flatulence across the three studies even on control diets without flatulence-producing components. Conclusions People's concerns about excessive flatulence from eating beans may be exaggerated. Public health nutritionists should address the potential for gastrointestinal discomfort when increasing fiber intake from beans with clients. It is important to recognize there is individual variation in response to different bean types.",
"title": "Perceptions of flatulence from bean consumption among adults in 3 feeding studies"
},
{
"docid": "MED-1880",
"text": "Legumes are the basés diet in several countries. They hold a high nutritional value, but other properties related to human health are nowadays being studied. The aim of this work was to study the influence of processes (boiling or germination) on the phenolic composition of dark beans (Phaseolus vulgaris L. c.v. Tolosana) and their effect on their antioxidant, neuroprotective and anticancer ability. Phenolic composition of raw and processed dark beans was analysed by HPLC-PAD and HPLC-ESI/MS. The antioxidant activity was evaluated by ORAC. Astrocytes cultures (U-373) have been used to test their neuroprotective effect. Anticancer activities were evaluated on three different cell lines (renal adenocarcinoma (TK-10), breast adenocarcinoma (MCF-7) and melanoma (UACC-62)) by sulphorhodamine B method. Qualitative and quantitative differences in phenolic composition have been observed between raw and processed dark beans that influence the antioxidant activity, mainly for germinated samples which show a decrease of antioxidant capacity. Although every assayed extracts decreased reactive oxygen species release and exhibited cytotoxicity activities on cancer cell lines, raw beans proved to be the most active in neuroprotective and antitumoral effects; this sample is especially rich in phenolic compounds, mainly anthocyanins. This study further demonstrated that phenolic composition of dark beans is related with cooking process and so with their neuroprotective and anticancer activity; cooking of dark beans improves their digestion and absorption at intestinal level, while maintaining its protective ability on oxidative process at cellular level. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Effect of cooking and germination on phenolic composition and biological properties of dark beans (Phaseolus vulgaris L.)."
},
{
"docid": "MED-3141",
"text": "OBJECTIVE: To evaluate the associations with chronic disease risk and mortality of the consequences of bean-free diets in Taiwanese adults with regard to gender. DESIGN: A sub-sample of the National Health Interview Survey (NHIS) in 2001 agreed to physical examination in the subsequent year. This group then took part in the Taiwanese Survey of Hyperglycaemia, Hyperlipidaemia and Hypertension (TwSHHH) in 2002. SETTING: Individual records were linked to the eventual death files from 2002 to 2008. SUBJECTS: Up to the end of 2008, a total of 2820 men and 2950 women were tracked by death registry over the 6·8 years of follow-up. RESULTS: Among 38,077 person-years, an average follow-up 6·5 years, 225 all-cause deaths were identified. Generalized linear models showed beans to be favourable for metabolic syndrome (other than for fasting glucose) in men; in women, beans were favourable for waist circumference and HbA1c. Cumulative logistic regression models for the effect of a bean-free diet on metabolic syndrome scores according to the Taiwanese-modified National Cholesterol Education Program-Adult Treatment Panel III (NCEP-tw) gave adjusted odds ratios of 1·83 in men and 1·45 in women. Cox regression models for the bean-free diet showed an increased hazard ratio for all-cause mortality among women (1·98, 95% CI 1·03, 3·81) but not men (1·28, 95% CI 0·76, 2·16). CONCLUSIONS: A bean-free diet may play a role in developing the metabolic syndrome in both genders, and is a significant predictor of all-cause mortality in Taiwanese women but not men.",
"title": "A bean-free diet increases the risk of all-cause mortality among Taiwanese women: the role of the metabolic syndrome."
},
{
"docid": "MED-5079",
"text": "OBJECTIVE: To determine effects of daily intake of 1/2 cup pinto beans, black-eyed peas or carrots (placebo) on risk factors for coronary heart disease (CHD) and diabetes mellitus (DM) in free-living, mildly insulin resistant adults over an 8 week period. METHODS: Randomized, crossover 3x3 block design. Sixteen participants (7 men, 9 women) received each treatment for eight-weeks with two-week washouts. Fasting blood samples collected at beginning and end of periods were analyzed for total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol, triacylglycerols, high-sensitivity C-reactive protein, insulin, glucose, and hemoglobin A1c. RESULTS: A significant treatment-by-time effect impacted serum TC (p = 0.026) and LDL (p = 0.033) after eight weeks. Paired t-tests indicated that pinto beans were responsible for this effect (p = 0.003; p = 0.008). Mean change of serum TC for pinto bean, black-eyed pea and placebo were -19 +/- 5, 2.5 +/- 6, and 1 +/- 5 mg/dL, respectively (p = 0.011). Mean change of serum LDL-C for pinto bean, black-eyed pea and placebo were -14 +/- 4, 4 +/- 5, and 1 +/- 4 mg/dL, in that order (p = 0.013). Pinto beans differed significantly from placebo (p = 0.021). No significant differences were seen with other blood concentrations across the 3 treatment periods. CONCLUSIONS: Pinto bean intake should be encouraged to lower serum TC and LDL-C, thereby reducing risk for CHD.",
"title": "Pinto bean consumption reduces biomarkers for heart disease risk."
},
{
"docid": "MED-2570",
"text": "The functional properties, including antioxidant and chemopreventative capacities as well as the inhibitory effects on angiotensin-converting enzyme (ACE), α-glucosidase and pancreatic lipase, of three Australian-grown faba bean genotypes (Nura, Rossa and TF(Ic*As)*483/13) were investigated using an array of in vitro assays. Chromatograms of on-line post column derivatisation assay coupled with HPLC revealed the existence of active phenolics (hump) in the coloured genotypes, which was lacking in the white-coloured breeding line, TF(Ic*As)*483/13. Roasting reduced the phenolic content, and diminished antioxidant activity by 10-40 % as measured by the reagent-based assays (diphenylpicrylhydrazyl, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) and oxygen radical absorbance capacity) in all genotypes. Cell culture-based antioxidant activity assay (cellular antioxidant activity) showed an increase of activity in the coloured genotypes after roasting. Faba bean extracts demonstrated cellular protection ability against H₂O₂-induced DNA damage (assessed using RAW264.7 cells), and inhibited the proliferation of all human cancer cell lines (BL13, AGS, Hep G2 and HT-29) evaluated. However, the effect of faba bean extracts on the non-transformed human cells (CCD-18Co) was negligible. Flow cytometric analyses showed that faba bean extracts successfully induced apoptosis of HL-60 (acute promyelocytic leukaemia) cells. The faba bean extracts also exhibited ACE, α-glucosidase and pancreatic lipase inhibitory activities. Overall, extracts from Nura (buff-coloured) and Rossa (red-coloured) were comparable, while TF(Ic*As)*483/13 (white-coloured) contained the lowest phenolic content and exhibited the least antioxidant and enzyme inhibition activities. These results are important to promote the utilisation of faba beans in human diets for various health benefits.",
"title": "In vitro investigations of the potential health benefits of Australian-grown faba beans (Vicia faba L.): chemopreventative capacity and inhibitory ..."
},
{
"docid": "MED-3136",
"text": "The objective of this study was to determine the influence of frequent and long-term consumption of legume seeds on colonic function. Two groups of subjects were studied--one group habitually consumed legume seeds as part of their normal diet, a second group only infrequently consumed legumes. No differences between these groups could be detected for fecal output and frequency, intestinal transit time, VFA excretion or fecal pH during 23-day study periods in which subjects consumed either their usual diet or 100 g red kidney beans, daily. However, the addition of beans to the diets of both groups provided significantly more dietary fiber, and produced greater fecal output and a higher concentration of VFA in feces. Fecal output appeared to be determined by two independent parameters--dietary fiber intake and VFA excretion. Beans provided a physiologically useful source of dietary fiber and favorably influenced colonic function.",
"title": "Influence of frequent and long-term bean consumption on colonic function and fermentation."
},
{
"docid": "MED-2147",
"text": "Consumption of Phaseolus vulgaris bean species such as pinto, black, navy or kidney may be beneficial in the prevention and treatment of chronic diseases. In particular, conditions that are promoted by increased glycaemic stress (hyperglycaemia and hyperinsulinaemia) including diabetes, CVD and cancer seem to be reduced in individuals who eat more of these beans. The present paper discusses the influence of P. vulgaris species on glycaemic response and the impact that relationship may have on the risk of developing diabetes, CVD and cancer.",
"title": "Phaseolus beans: impact on glycaemic response and chronic disease risk in human subjects."
},
{
"docid": "MED-2580",
"text": "Adequate fruit and vegetable intake was suggested to protect against colorectal cancer and colorectal adenomas; however, several recent prospective studies reported no association. We examined the association between fruits and vegetables and adenomatous polyp recurrence in the Polyp Prevention Trial (PPT). The PPT was a low-fat, high-fiber, high-fruit, and vegetable dietary intervention trial of adenoma recurrence, in which there were no differences in the rate of adenoma recurrence in participants in the intervention and control arms of the trial. In this analysis of the entire PPT trial–based cohort, multiple logistic regression analysis was used to estimate the odds ratio (OR) of advanced and nonadvanced adenoma recurrence within quartiles of baseline and change (baseline minus the mean over 3 y) in fruit and vegetable intake, after adjustment for age, total energyy intake, use of nonsteroidal anti-inflammatory drugs, BMI, and gender. There were no significant associations between nonadvanced adenoma recurrence and overall change in fruit and vegetable consumption; however, those in the highest quartile of change in dry bean intake (greatest increase) compared with those in the lowest had a significantly reduced OR for advanced adenoma recurrence (OR = 0.35; 95% CI, 0.18–0.69; P for trend = 0.001). The median in the highest quartile of change in dry bean intake was 370% higher than the baseline intake. The PPT trial–based cohort provides evidence that dry beans may be inversely associated with advanced adenoma recurrence.",
"title": "High Dry Bean Intake and Reduced Risk of Advanced Colorectal Adenoma Recurrence among Participants in the Polyp Prevention Trial"
},
{
"docid": "MED-2144",
"text": "Bean pods (Phaseolus vulgaris) are among the most widely used traditional remedies against diabetes mellitus. Historical knowledge is summarized and compared to recent study results. Reports dating from the first half of the 20(th) century as well as recent publications show contradictory results. It seems that Phaseolus preparations should not be considered the first choice in phytopharmaceutical treatment of diabetes or lead structure research. To be effective, fairly high doses of aqueous extracts need to be given. Because of their fiber content and an alpha-amylase inhibitory effect, beans might be more useful as food components in preventing or ameliorating type 2 diabetes.",
"title": "Beans and diabetes: Phaseolus vulgaris preparations as antihyperglycemic agents."
},
{
"docid": "MED-2010",
"text": "Legumes (including alfalfa, clover, lupins, green beans and peas, peanuts, soybeans, dry beans, broad beans, dry peas, chickpeas, and lentils) represent an important component of the human diet in several areas of the world, especially in the developing countries, where they complement the lack of proteins from cereals, roots, and tubers. In some regions of the world, legume seeds are the only protein supply in the diet. The health benefits of legume consumption have received rising interest from researchers, and their consumption and production extends worldwide. Among European countries, higher legume consumption is observed around the Mediterranean, with per capita daily consumption between 8 and 23 g, while in Northern Europe, the daily consumption is less than 5 g per capita. The physiological effects of different legumes vary significantly. These differences may result from the polysaccharides composition, in particular, the quantity and variety of dietary fibers and starch, protein make-up, and variability in phytochemical content. The majority of legumes contain phytochemicals: bioactive compounds, including enzyme inhibitors, phytohemagglutinins (lectins), phytoestrogens, oligosaccharides, saponins, and phenolic compounds, which play metabolic roles in humans who frequently consume these foods. Dietary intake of phytochemicals may provide health benefits, protecting against numerous diseases or disorders, such as coronary heart disease, diabetes, high blood pressure and inflammation. The synergistic or antagonistic effects of these phytochemical mixtures from food legumes, their interaction with other components of the diet, and the mechanism of their action have remained a challenge with regard to understanding the role of phytochemicals in health and diseases. Their mitigating effects and the mechanism of their action need to be further addressed if we are to understand the role of phytochemicals in health and diseases. This review provides an overview of the nutritional quality of legumes and their potential contribution in cardiometabolic risk prevention.",
"title": "Nutritional quality of legumes, and their role in cardiometabolic risk prevention: a review."
},
{
"docid": "MED-5078",
"text": "In this study, solid fermentation of steamed black soybean with various GRAS (Generally recognized as safe) filamentious-fungi including Aspergillus awamori, Aspergillus oryzae BCRC 30222, Aspergillus sojae BCRC 30103, Rhizopus azygosporus BCRC 31158 and Rhizopus sp. No. 2 was performed. Mutagenicity and antimutagenicity of the methanol extracts of unfermented and fermented steamed black soybeans against 4-nitroquinoline-N-oxide (4-NQO), a direct mutagen and Benzo[a]pyrene (B[a]P), an indirect mutagen, on Salmonella Typhimurium TA100 and TA 98, were examined. The methanol extracts of unfermented and fermented steamed black soybeans show no mutagenic activity for either test strains at the doses tested. The extracts inhibited mutagenesis by either 4-NQO or B[a]P in S. Typhimurium TA100 and TA98. Fermentation with fungi also enhanced the antimutagenic effect of black soybean while the antimutagenic effect of the fermented black soybeans extract varied with the starter organism, mutagen, and test strain of S. Typhimurium examined. Generally, the extracts of A. awamori-fermented black soybean exhibited the highest antimutagenic effect. With strain TA100, the inhibitory effects of 5.0 mg of A. awamori-fermented black soybean extract per plate on the mutagenic effects of 4-NQO and B[a]P were 92% and 89%, respectively, while the corresponding rates for extract of unfermented were 41% and 63%, respectively. With strain 98, the inhibition rates were 94 and 81% for the fermented bean extract and 58% and 44% for the unfermented bean extracts. Testing of extracts prepared from black soybean by A. awamori at temperatures 25, 30 and 35 degrees C and for times of 1-5 days revealed that, generally, the extract prepared from beans fermented at 30 degrees C for 3 days exhibited the greatest inhibition against the mutagenic effects of 4-NQO and B[a]P.",
"title": "Mutagenic and antimutagenic effects of methanol extracts of unfermented and fermented black soybeans."
},
{
"docid": "MED-2141",
"text": "We investigated the association between dietary patterns and insulin resistance in the 3871 healthy Korean adults from the 2007 to 2008 Korea National Health and Nutrition Examination Survey. The whole grains and beans pattern was associated with lower prevalence of insulin resistance (OR for highest quintile=0.80, 95% CI=0.61-1.03, P for trend=0.013). Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.",
"title": "High intake of whole grains and beans pattern is inversely associated with insulin resistance in healthy Korean adult population."
},
{
"docid": "MED-5080",
"text": "Bioactivity-guided fractionation of black bean (Phaseolus vulgaris) seed coats was used to determine the chemical identity of bioactive constituents, which showed potent antiproliferative and antioxidative activities. Twenty-four compounds including 12 triterpenoids, 7 flavonoids, and 5 other phytochemicals were isolated using gradient solvent fractionation, silica gel and ODS columns, and semipreparative and preparative HPLC. Their chemical structures were identified using MS, NMR, and X-ray diffraction analysis. Antiproliferative activities of isolated compounds against Caco-2 human colon cancer cells, HepG2 human liver cancer cells, and MCF-7 human breast cancer cells were evaluated. Among the compounds isolated, compounds 1, 2, 6, 7, 8, 13, 14, 15, 16, 19, and 20 showed potent inhibitory activities against the proliferation of HepG2 cells, with EC50 values of 238.8 +/- 19.2, 120.6 +/- 7.3, 94.4 +/- 3.4, 98.9 +/- 3.3, 32.1 +/- 6.3, 306.4 +/- 131.3, 156.9 +/- 11.8, 410.3 +/- 17.4, 435.9 +/- 47.7, 202.3 +/- 42.9, and 779.3 +/- 37.4 microM, respectively. Compounds 1, 2, 3, 5, 6, 7, 8, 9, 10, 11, 14, 15, 19, and 20 showed potent antiproliferative activities against Caco-2 cell growth, with EC50 values of 179.9 +/- 16.9, 128.8 +/- 11.6, 197.8 +/- 4.2, 105.9 +/- 4.7, 13.9 +/- 2.8, 35.1 +/- 2.9, 31.2 +/- 0.5, 71.1 +/- 11.9, 40.8 +/- 4.1, 55.7 +/- 8.1, 299.8 +/- 17.3, 533.3 +/- 126.0, 291.2 +/- 1.0, and 717.2 +/- 104.8 microM, respectively. Compounds 5, 7, 8, 9, 11, 19, 20 showed potent antiproliferative activities against MCF-7 cell growth in a dose-dependent manner, with EC50 values of 129.4 +/- 9.0, 79.5 +/- 1.0, 140.1 +/- 31.8, 119.0 +/- 7.2, 84.6 +/- 1.7, 186.6 +/- 21.1, and 1308 +/- 69.9 microM, respectively. Six flavonoids (compounds 14-19) showed potent antioxidant activity. These results showed the phytochemical extracts of black bean seed coats have potent antioxidant and antiproliferative activities.",
"title": "Phytochemicals of black bean seed coats: isolation, structure elucidation, and their antiproliferative and antioxidative activities."
},
{
"docid": "MED-3132",
"text": "Little is known about dietitians current practice in counselling clients about the use of legumes in a low fat, high fibre diet. An exploratory e-mail questionnaire was sent to members of Dietitians of Canada to assess: dietitian use and preferences for legumes, dietitian practice, opinions about clients attitudes and preferences, and resource needs. Counsellors (n=256) had high personal use of legumes (64% > or = 1 serving/week) and frequently recommended legumes in counselling. The legumes most preferred by respondents and their clients were: peanuts, kidney beans, split peas, chickpeas, and lentils. Respondents often recommended canned bean products (76%) and tofu (61%), but other legume grocery products were less often recommended. The most common client issues identified were: flatulence (87% agreed), lack of familiarity (85%), and knowledge of preparation (82%). Dietitians were not satisfied with current resources to support practice, especially those respondents providing primarily clinical counselling services. The most requested resources were: recipes (90%), pamphlets (82%), food demonstrations (75%) and Internet sites (63%). Client level research is now needed to confirm the importance of the issues identified and to develop and test strategies for legume promotion in counselling.",
"title": "Legume promotion in counselling: an e-mail survey of dietitians."
},
{
"docid": "MED-2085",
"text": "A diet rich in fruits and vegetables is known to decrease the risk of cardiovascular disease. However, the information regarding the antithrombotic activity (antiplatelet, anticoagulant, and fibrinolytic) of fruits and vegetables is scarce. The aim of this study was to assess the antithrombotic activity of extracts from fruits and vegetables widely consumed in central Chile. The study included samples of 19 fruits and 26 vegetables, representative of the local diet. The extracts prepared from each sample included an aqueous (juice or pressed solubles) and/or methanol-soluble fraction. The extracts were evaluated for antiplatelet, anticoagulant, and fibrinolytic activity in vitro at a final concentration of 1 mg/ml. The antiplatelet activity was assessed by platelet aggregation inhibition; anticoagulant activity was measured by the prothrombin time (PT), diluted prothrombin time (dPT), activated partial thromboplastin time (APTT), kaolin clotting time (KCT), and thrombin time. The fibrinolytic effect was determined with the euglobin clot lysis time and fibrin plate methods. Extracts of green beans and tomatoes inhibited platelet aggregation induced by ADP and arachidonic acid, in a concentration-dependent manner. The methanolic extracts of grapes prolonged the PT and dPT. Finally, extracts of raspberry prolonged the APTT and also presented fibrinolytic activity. In conclusion, from a screening that included a variety of fruits and vegetables, we found antiplatelet activity in green beans and tomatoes, anticoagulant activities in grapes and raspberries, whereas fibrinolytic activity was observed only in raspberries. Further investigations are necessary to advance in knowledge of the active compounds of these fruits and vegetables and their mechanisms of action.",
"title": "Antiplatelet, anticoagulant, and fibrinolytic activity in vitro of extracts from selected fruits and vegetables."
},
{
"docid": "MED-5118",
"text": "OBJECTIVE: To compare the effects of two commercially available soy milks (one made using whole soy beans, the other using soy protein isolate) with low-fat dairy milk on plasma lipid, insulin, and glucose responses. DESIGN: Randomized clinical trial, cross-over design. SUBJECTS: Participants were 30-65 years of age, n = 28, with pre-study LDL-cholesterol (LDL-C) concentrations of 160-220 mg/dL, not on lipid lowering medications, and with an overall Framingham risk score of <or=10%. INTERVENTION: Participants were required to consume sufficient milk to provide 25 g protein/d from each source. The protocol included three 4-week treatment phases, each separated from the next by a wash-out period of >or=4 weeks. RESULTS: Mean LDL-C concentration at the end of each phase (+/- SD) was 161 +/- 20, 161 +/- 26 and 170 +/- 24 mg/dL for the whole bean soy milk, the soy protein isolate milk, and the dairy milk, respectively (p = 0.9 between soy milks, p = 0.02 for each soy milk vs. dairy milk). No significant differences by type of milk were observed for HDL-cholesterol, triacylglycerols, insulin, or glucose. CONCLUSION: A 25 g dose of daily soy protein from soy milk led to a modest 5% lowering of LDL-C relative to dairy milk among adults with elevated LDL-C. The effect did not differ by type of soy milk and neither soy milk significantly affected other lipid variables, insulin or glucose.",
"title": "Effect of two types of soy milk and dairy milk on plasma lipids in hypercholesterolemic adults: a randomized trial."
},
{
"docid": "MED-3894",
"text": "The purpose of this study was to examine the effects of a natural carbohydrate (CHO) source in the form of sun-dried raisins (SDRs) vs. Sports Jelly Beans™ (SJBs) on endurance performance in trained cyclists and triathletes. Ten healthy men (18-33 years) completed 1 water-only acclimatization exercise trial and 2 randomized exercise trials administered in a crossover fashion. Each trial consisted of a 120-minute constant-intensity glycogen depletion period followed by a 10-km time trial (TT). During each experimental trial, participants consumed isocaloric amounts of SDRs or SJBs in 20-minute intervals. Measurements included time to complete 10-km TT, power output during 10-km TT, blood glucose levels and respiratory exchange ratio during glycogen depletion period, rate of perceived exertion (RPE), 'flow' questionnaire responses, and a hedonic (i.e., pleasantness) sensory acceptance test. There were no significant differences in endurance performance for TT time (SDRs vs. SJBs, 17.3 ± 0.4 vs. 17.3 ± 0.4 seconds) or power (229.3 ± 13.0 vs. 232.0 ± 13.6 W), resting blood glucose levels (5.8 ± 04 mmol·L(-1) for SDRs and 5.4 ± 0.2 mmol·L(-1) for SJBs), RPE, or flow experiences between SDR and SJB trials. However, the mean sensory acceptance scores were significantly higher for the SDRs compared to the SJBs (50.7 ± 1.7 vs. 44.3 ± 2.7). Consuming SDRs or SJBs during 120 minutes of intense cycling results in similar subsequent TT performances and are equally effective in maintaining blood glucose levels during exercise. Therefore, SDRs are a natural, pleasant, cost-effective CHO alternative to commercial SJBs that can be used during moderate- to high-intensity endurance exercise.",
"title": "Sun-dried raisins are a cost-effective alternative to Sports Jelly Beans in prolonged cycling."
},
{
"docid": "MED-4869",
"text": "This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of various food additives, including flavouring agents, with a view to recommending acceptable daily intakes (ADIs) and to preparing specifications for identity and purity. The first part of the report contains a general discussion of the principles governing the toxicological evaluation and assessment of intake of food additives (in particular, flavouring agents). A summary follows of the Committee's evaluations of technical, toxicological and intake data for certain food additives (asparaginase from Aspergillus niger expressed in A. niger, calcium lignosulfonate (40-65), ethyl lauroyl arginate, paprika extract, phospholipase C expressed in Pichia pastoris, phytosterols, phytostanols and their esters, polydimethylsiloxane, steviol glycosides and sulfites [assessment of dietary exposure]) and 10 groups of related flavouring agents (aliphatic branched-chain saturated and unsaturated alcohols, aldehydes, acids and related esters; aliphatic linear alpha,beta-unsaturated aldehydes, acids and related alcohols, acetals and esters; aliphatic secondary alcohols, ketones and related esters; alkoxy-substituted allylbenzenes present in foods and essential oils and used as flavouring agents; esters of aliphatic acyclic primary alcohols with aliphatic linear saturated carboxylic acids; furan-substituted aliphatic hydrocarbons, alcohols, aldehydes, ketones, carboxylic acids and related esters, sulfides, disulfides and ethers; miscellaneous nitrogen-containing substances; monocyclic and bicyclic secondary alcohols, ketones and related esters; hydroxy- and alkoxy-substituted benzyl derivatives; and substances structurally related to menthol). Specifications for the following food additives were revised: canthaxanthin; carob bean gum and carob bean gum (clarified); chlorophyllin copper complexes, sodium and potassium salts; Fast Green FCF; guar gum and guar gum (clarified); iron oxides; isomalt; monomagnesium phosphate; Patent Blue V; Sunset Yellow FCF; and trisodium diphosphate. Re-evaluation of flavouring agents for which estimated intake was based on anticipated poundage data was carried out for 2-isopropyl- N,2,3-trimethylbutyramide (No. 1595) and L-monomenthyl glutarate (No. 1414). Annexed to the report are tables summarizing the Committee's recommendations for intakes and toxicological evaluations of the food additives considered.",
"title": "Evaluation of certain food additives."
},
{
"docid": "MED-2150",
"text": "Previous investigations, of adolescent diet recalled in adulthood, found lower risk for benign breast disease (BBD) with higher intakes of vegetable fat and nuts during high school. We investigate whether vegetable protein and fat, derived from diets reported during pre-adolescence and adolescence, are associated with subsequent risk for BBD in young women. The Growing Up Today Study includes 9,039 females, 9–15 years in 1996, who completed questionnaires annually through 2001, and then in 2003, 2005, 2007, and 2010. Food frequency questionnaires (1996–2001) obtained intake data on a variety of foods. Beginning in 2005, women (18–30 years) reported whether they had ever been diagnosed with BBD that was confirmed by breast biopsy (n = 112 cases). Logistic regression estimated associations between intakes of vegetable protein and fat and biopsy-confirmed BBD. Those individual foods that were the largest contributors of protein and fat in this cohort were also investigated. In analyses of intakes from 1996 through 1998, when our cohort was youngest, vegetable fat (OR = 0.72/(10 gm/day), 95 % CI 0.53–0.98; p = 0.04) was inversely associated with BBD risk. The greatest sources of vegetable fat and protein in these girls were peanut butter, peanuts, nuts, beans (beans, lentils, and soybeans), and corn. A daily serving of any one of these was associated with lower risk (OR = 0.32/(serv/day), 95 % CI 0.13–0.79; p = 0.01). Peanut butter (and nuts) at age 11 years was inversely associated with risk (p = 0.01). In analyses of intakes at age 14 years, vegetable protein was associated with lower BBD risk (OR = 0.64/(10 gm/day), 95 % CI 0.43–0.95; p = 0.03). A daily serving at 14 years of any one of the foods was associated with lower risk (OR = 0.34, 95 % CI 0.16–0.75; p = 0.01), as was peanut butter (and nuts) (p = 0.02). Girls with a family history of breast cancer had significantly lower risk if they consumed these foods or vegetable fat. In conclusion, consumption of vegetable protein, fat, peanut butter, or nuts by older girls may help reduce their risk of BBD as young women.",
"title": "Vegetable protein and vegetable fat intakes in pre-adolescent and adolescent girls, and risk for benign breast disease in young women"
},
{
"docid": "MED-719",
"text": "In addition to causing embarrassment and unease, flatulence is linked to a variety of symptoms, some of which may be distressing. This review describes the origins of intestinal gas, its composition and methods which have been developed for its analysis. Emphasis is placed upon the effects of legumes in the diet in producing excessive intestinal gas and, particularly, on the role of raffinose-type oligosaccharides, containing alpha-galactosidic groupings. Suggestions for overcoming the problem are presented, including drug treatment, enzyme treatment, food processing and plant breeding. It is emphasised that removal of all raffinose-oligosaccharides from beans does not remove the problem of flatulence in animals and man; the compounds responsible--though assumed to be polysaccharides (or polysaccharide-derived oligomers formed by processing or cooking)--have yet to be characterised.",
"title": "Flatulence--causes, relation to diet and remedies."
},
{
"docid": "MED-724",
"text": "In addition to causing embarrassment and unease, flatulence is linked to a variety of symptoms, some of which may be distressing. This review describes the origins of intestinal gas, its composition and methods which have been developed for its analysis. Emphasis is placed upon the effects of legumes in the diet in producing excessive intestinal gas and, particularly, on the role of raffinose-type oligosaccharides, containing alpha-galactosidic groupings. Suggestions for overcoming the problem are presented, including drug treatment, enzyme treatment, food processing and plant breeding. It is emphasised that removal of all raffinose-oligosaccharides from beans does not remove the problem of flatulence in animals and man; the compounds responsible--though assumed to be polysaccharides (or polysaccharide-derived oligomers formed by processing or cooking)--have yet to be characterised.",
"title": "Flatulence--causes, relation to diet and remedies."
},
{
"docid": "MED-890",
"text": "A case-control study was carried out in Harbin city to assess the role of diet in the aetiology of colorectal cancer. A total of 336 incident cases of histologically confirmed colorectal cancer (111 colon cancer and 225 rectal cancer) and an equal number of controls with other non-neoplastic diseases were interviewed in hospital wards. Data concerning the average frequency of consumption and amount consumed of single food items were obtained by a dietary history questionnaire. Odds ratios and their confidence limits were computed. Multiple regression for risk status was also used. Vegetables, particularly green vegetables, chives and celery, have a strong protective effect against colorectal cancer. Reduced consumption of meat, eggs, bean products and grain was associated with increasing risk for cancer of the rectum. Alcohol intake was found to be an important risk factor for developing colon cancer and male rectal cancer.",
"title": "Diet and cancer of the colon and rectum: a case-control study in China."
},
{
"docid": "MED-4165",
"text": "Ergothioneine is a native membrane-impermeable thiol compound that is specifically accumulated in cells via the organic cation transporter OCTN1. In humans, OCTN1 and ergothioneine have been implicated in the etiopathogenesis of autoimmune disorders. However, available evidence about dietary sources and the functional role of ergothioneine in human physiology is scarce. Here, we analyzed the ergothioneine content in common foods using liquid chromatography tandem-mass spectrometry. Additionally, we assessed the protective potency of ergothioneine against various oxidative stressors in OCTN1-expressing cells in comparison with the main intracellular thiol antioxidant glutathione by evaluating cell viability with the MTT reduction assay. Only some food contained ergothioneine with highest concentrations detected in specialty mushrooms, kidney, liver, black and red beans, and oat bran. Ergothioneine exhibited cell protection only against copper(II)-induced toxicity but was far less potent than glutathione, indicting that ergothioneine is not involved in the intracellular antioxidant thiol defense system.",
"title": "Dietary sources and antioxidant effects of ergothioneine."
},
{
"docid": "MED-875",
"text": "AIMS: The purpose of this study was to search for a novel quorum sensing inhibitor and analyse its inhibitory activity. METHODS AND RESULTS: Quorum sensing inhibition was monitored using the Tn-5 mutant, Chromobacterium violaceum CV026. Vanilla beans (Vanilla planifolia Andrews) were extracted using 75% (v/v) aqueous methanol and added to C. violaceum CV026 cultures. Inhibitory activity was measured by quantifying violacein production using a spectrophotometer. The results have revealed that vanilla extract significantly reduced violacein production in a concentration-dependent manner, indicating inhibition of quorum sensing. CONCLUSIONS: Vanilla, a widely used spice and flavour, can inhibit bacterial quorum sensing. SIGNIFICANCE AND IMPACT OF THE STUDY: The results suggest that the intake of vanilla-containing food materials might promote human health by inhibiting quorum sensing and preventing bacterial pathogenesis. Further studies are required to isolate specific substances from vanilla extract acting as quorum sensing inhibitors.",
"title": "Inhibition of bacterial quorum sensing by vanilla extract."
},
{
"docid": "MED-5354",
"text": "This review focuses on the possible role in human health of the consumption of lignan-rich foods. Most of the plant lignans in human foods are converted by the intestinal microflora in the upper part of the large bowel to enterolactone and enterodiol, called mammalian or enterolignans. The protective role of these compounds, particularly in chronic Western diseases, is discussed. Evidence suggests that fiber- and lignan-rich whole-grain cereals, beans, berries, nuts, and various seeds are the main protective foods. Many factors, in addition to diet, such as intestinal microflora, smoking, antibiotics, and obesity affect circulating lignan levels in the body. Lignan-rich diets may be beneficial, particularly if consumed for life. Experimental evidence in animals has shown clear anticarcinogenic effects of flaxseed or pure lignans in many types of cancer. Many epidemiological results are controversial, partly because the determinants of plasma enterolactone are very different in different countries. The source of the lignans seems to play a role because other factors in the food obviously participate in the protective effects. The results are promising, but much work is still needed in this area of medicine.",
"title": "Lignans and human health."
},
{
"docid": "MED-2195",
"text": "The objective of this study was to evaluate the precursors of acrylamide formation in sweet potato (SP) (Ipomoea batatas L. Lam) chips and to determine the effect of different types of vegetable oils (VOs), that is, palm olein, coconut oil, canola oil, and soya bean oil, on acrylamide formation. The reducing sugars and amino acids in the SP slices were analyzed, and the acrylamide concentrations of SP chips were measured. SP chips that were fried in a lower degree of unsaturation oils contained a lower acrylamide concentration (1443 μg/kg), whereas those fried with higher degree of unsaturated oils contained a higher acrylamide concentration (2019 μg/kg). SP roots were found to contain acrylamide precursors, that is, 4.17 mg/g glucose and 5.05 mg/g fructose, and 1.63 mg/g free asparagine. The type of VO and condition used for frying, significantly influenced acrylamide formation. This study clearly indicates that the contribution of lipids in the formation of acrylamide should not be neglected. © 2013 Institute of Food Technologists®",
"title": "The influence of deep frying using various vegetable oils on acrylamide formation in sweet potato (Ipomoea batatas L. Lam) chips."
},
{
"docid": "MED-1150",
"text": "The “organic food” market is the fastest growing food sector, yet it is unclear whether organically raised food is nutritionally superior to conventionally grown food and whether consuming organic food bestows health benefits. In order to evaluate potential health benefits of organic foods, we used the well-characterized fruit fly Drosophila melanogaster as a model system. Fruit flies were raised on a diets consisting of extracts of either conventionally or organically raised produce (bananas, potatoes, raisins, soy beans). Flies were then subjected to a variety of tests designed to assess overall fly health. Flies raised on diets made from organically grown produce had greater fertility and longevity. On certain food sources, greater activity and greater stress resistance was additionally observed, suggesting that organic food bestows positive effects on fly health. Our data show that Drosophila can be used as a convenient model system to experimentally test potential health effects of dietary components. Using this system, we provide evidence that organically raised food may provide animals with tangible benefits to overall health.",
"title": "Organically Grown Food Provides Health Benefits to Drosophila melanogaster"
},
{
"docid": "MED-720",
"text": "Bloating, abdominal distention, and flatulence represent very frequent complaints in functional disorders but their pathophysiology and treatment are largely unknown. Patients frequently associate these symptoms with excessive intestinal gas and the reduction of gas production may represent an effective strategy. The aim was to evaluate the effect of alpha-galactosidase administration, in a randomized double-blind placebo-controlled protocol, on intestinal gas production and gas-related symptoms after a challenge test meal in healthy volunteers. Eight healthy volunteers ingested 300 or 1200 GalU of alpha-galactosidase or placebo during a test meal containing 420 g of cooked beans. Breath hydrogen excretion and occurrence of bloating, abdominal pain, discomfort, flatulence, and diarrhea were measured for 8 hr. The administration of 1200 GalU of alpha-galactosidase induced a significant reduction of both breath hydrogen excretion and severity of flatulence. A reduction in severity was apparent for all considered symptoms, but both 300 and 1200 GalU induced a significant reduction in the total symptom score. Alpha-galactosidase reduced gas production following a meal rich in fermentable carbohydrates and may be helpful in patients with gas-related symptoms.",
"title": "The effect of oral alpha-galactosidase on intestinal gas production and gas-related symptoms."
}
] |
10031
|
Moving from India to Europe - Bank accounts and Mutual funds
|
[
{
"docid": "467169",
"text": "Once you become NRI or know for sure you would be one, you can't hold ordinary accounts. Convert existing savings account into NRO. Open new NRE account so it's easier to move funds. In simple terms an NRE type of account means you can repatriate the funds outside of India anytime without any paperwork, there are some tax benefits as well. MFU platform can be used for operating demat, else you need a brokerage account. If you have stocks, then existing demat need to be converted to NONPINS account, it's actually open new, move, close old. Any new stock you need to open a PINS Demat account. You can use NRO account of MFU, it creates some complexity of taxes... MFU NRE would be more easier for taxes and flexible for repatriation",
"title": ""
}
] |
[
{
"docid": "16068",
"text": "I have not opened any NRE/NRO account before coming to Finland. This is in violation of Foreign Exchange Management Act. Please get this regularized ASAP. All your savings account need to be converted to NRO. Shall I transfer funds from abroad to both NRE and NRO account or I can transfer only to NRE account in India? You can transfer to NRE or NRO. It is advisable to transfer into NRE as funds from here can be repatriated out of India without any paperwork. Funds from NRO account need paperwork to move out of India. I am a regular tax payer in abroad. The Funds which i'll transfer in future will attract any additional tax in India? As your status is Non Resident and the income is during that period, there is no tax applicable in India on this. Few Mutual Fund SIPs (monthly basis) are linked with my existing saving account in india. Do these SIPs will stop when the savings account will turn into NRO account? Shall I need to submit any documents for KYC compliance? If yes, to whom I should submit these? is there any possibility to submit it Online? Check your Bank / Mutual Fund company. Couple of FDs are also opened online and linked with this existing saving account. Do the maturity amount(s) subject to TDS or any tax implication such as 30.9% as this account will be turned into NRO account till that time and NRO account attracts this higher tax percentage. These are subject to taxes in India. This will be as per standard tax brackets. Which account (NRE/NRO) is better for paying EMIs for Home Loan, SIPs of Mutual Funds, utility bills in India, transfer money to relative's account etc Home Loan would be better from NRE account as if you sell the house, the EMI paid can be credited into NRE account and you can transfer this out of India without much paperwork. Same for SIP's. For other it doesn't really matter as it is an expense. Is there any charge to transfer fund from NRE to NRO account if both account maintain in same Bank same branch. Generally No. Check with your bank. Which Bank account's (NRE/NRO) debit/ATM card should be used in Abroad in case of emergency. Check with your bank. NRE funds are more easy. NRO there will be limits and reporting. Do my other savings accounts, maintained in different Banks, also need to be converted into NRO account? If yes, how can it be done from Abroad? Yes. ASAP. Quite a few leading banks allow you to do this if you are not present. Check you bank for guidance.",
"title": ""
},
{
"docid": "312191",
"text": "How would I go about doing this? Assuming you had purchased the house by funding from your NRE account, you can easily move back the 30K into NRE Account and out of India from NRI Account. The 30K profit would be taxed in India as per capital gains and can only be moved into NRO account. A CA would need to certify that appropriate taxes have been withheld before the bank will release the funds for repatriation out of India. There is also a limit [large 1 million USD] on how much funds can be moved out of India. Consult a CA who would help you with the formalities. If you have not funded the purchase from NRE account, the entire proceeds should be into NRO account and then move funds from there.",
"title": ""
},
{
"docid": "521753",
"text": "I am on employment based visa in USA and want to send dollars from USA to India from my savings (after paying Tax). How much maximum dollars I can send in a day? month? or in a year regularly? There is no such limit. You can transfer as money you like to yourself anywhere. To pay the Bank Loan-student Loan how much maximum dollars I can send in a day, in a month or in a year? to pay that I have to pay directly to that Bank Account or in any account I can send money? You can transfer to your NRE account in India and move it further. You can also send it directly to the Loan Account [Check with the Bank, they may not be able to receive funds from outside for a Loan Account] My mother is having Green Card. She is not working. She has a NRE account in India. Can I send dollars from my USA Bank account to her NRE account in India? what are the rules for that? any Tax or limit for that? Or I have to get any permission before sending it? If you are sending money to your mother, it would come under Gift Tax act in US. There is no issue in India. Suggest you transfer to your own NRE account.",
"title": ""
},
{
"docid": "203889",
"text": "We have a house here in India worth Rs. 2 Crores. We want to sell it and take money with us. Selling the house in India will attract Capital Gains Tax. Essentially the price at which you sell the property less of the property was purchased [or deemed value when inherited by you]. The difference is Capital Gains. You have to pay tax on this gains. This is currently at 10% without Indexation and 20% with Indexation. Please note if you hold these funds for more than an year, you would additionally be liable for Wealth tax at 1% above Rs 50 lacs. Can I gift this whole amount to my US Citizen Daughter or what is the maximum limit of Gift amount What will be the tax liability on me and on my Daughter in case of Gift Whether I have to show it in my Income Tax Return or in my Daughter's Tax Return. What US Income Tax Laws says. What will be the procedure to send money as Gift to my Daughter. Assuming you are still Indian citizen when to gift the funds; From Indian tax point of you there is no tax to you. As you daughter is US citizen, there is no gift tax to her. There is no limit in India or US. So you can effectively gift the entire amount without any taxes. If you transfer this after you become a US Resident [for tax purposes], then there is a limit of USD 14,000/- per year per recipient. Effective you can gift your daughter and son-in-law 14,000/- ea and your husband can do the same. Net 14,000 * 4 USD per year. Beyond this you either pay tax or declare this and deduct it from life time estate quota. Again there is no tax for your daughter. What are the routes to take money from India to US Will the money will go directly from my Bank Act.to my Daughter's Bank Account. Will there will be wire transfer from bank to bank Can I send money through other money sender Certified Companies also. The best way is via Bank to Bank transfer. A CA Certificate is required to certify that taxes have been paid on this funds being transferred. Under the liberalized remittance scheme in India, there is a limit of USD 1 Million per year for moving funds outside of India. So you can move around Rs 6-7 Crore a year.",
"title": ""
},
{
"docid": "495315",
"text": "Is it possible to move money from NRE to NRO account Yes you can move money from NRE to NRO without any issue. You can't do the other way round. i.e. Move money from NRO to NRE. I would like to move USD earning to NRE Yes you can further move money in NRE to NRO account Yes you can I am planning to give NRO account to HDFC Home loan for EMI processing Yes you can. Depending on your long term plan it may not be a good idea. For example if you were to sell the house you cannot move the funds into NRE and outside of India without some amount of paperwork. However if you pay the EMI via NRE account, on the sale of house, you can transfer the funds into NRE account to the extent of the loan paid and the Original downpayment [if made from NRE account]. also I can deposit money from other savings account to NRO; As an NRI, you can't hold ordinary savings account in India. This is violation of norms. Please have any/all savings account in India converted to NRO at the earliest.",
"title": ""
},
{
"docid": "187734",
"text": "\"The Option 2 in your answer is how most of the money is moved cross border. It is called International Transfer, most of it carried out using the SWIFT network. This is expensive, at a minimum it costs in the range of USD 30 to USD 50. This becomes a expensive mechanism to transfer small sums of money that individuals are typically looking at. Over a period of years, the low value payments by individuals between certain pair of countries is quite high, example US-India, US-China, Middle-East-India, US-Mexico etc ... With the intention to reduce cost, Banks have built a different work-flow, this is the Option 1. This essentially works on getting money from multiple individuals in EUR. The aggregated sum is converted into INR, then transferred to partner Bank in India via Single SWIFT. Alongside the partner bank is also sent a file of instructions having the credit account. The Partner Bank in India will use the local clearing network [these days NEFT] to credit the funds to the Indian account. Option 3: Other methods include you writing a check in EUR and sending it over to a friend/relative in India to deposit this into Indian Account. Typically very nominal costs. Typically one month of timelines. Option 4: Another method would be to visit an Indian Bank and ask them to issue a \"\"Rupee Draft/Bankers Check\"\" payable in India. The charges for this would be higher than Option 3, less than Option 1. Mail this to friend/relative in India to deposit this into Indian Account. Typically couple of days timelines for transfer to happen.\"",
"title": ""
},
{
"docid": "448981",
"text": "am I allowed to transfer into NRE account from paypal? Credits into NRE accounts are restricted. It has to be established that the funds being credited are income outside of India. In case of paypal, paypal uses local clearing to credit funds into Bank Accounts. So essentially one cannot credit NRE account by domestic clearing network like NEFT. It is best that you withdraw the funds into Bank Account outside India and use SWIFT or remittance service to credit your NRE account. I do not want to transfer to an NRO account since the money credited into it will become taxable. This is not the right assumption. Credits into NRO are not taxable by default; if you establish that the funds are from outside India, there is no tax on the income money transferred from abroad into the NRO account. However, the interest that will be paid by the bank on the balance of the NRO account is taxable income in India and is subject to TDS. In contrast, interest paid on the balance in an NRE account is not taxable in India and is not subject to TDS as long as you maintain NRI status. However it does make sense to keep accounts segregated, i.e. income generated in India, credit the NRO account and income generated outside India credit to NRE.",
"title": ""
},
{
"docid": "146557",
"text": "What are the steps to bring the money to the US? It is worth 1.25 Crore and I have already paid the 20% tax in India. Under the Liberalized Remittance Scheme an Individual can repatriate funds upto USD 250,000 without any paperwork. However most banks would be cautious and request for Form 15CA and Form 15CB if you are moving funds from NRO Account. Form 15 CA you would need to declare why you are moving the said funds. The Form 15 CB is to be filled by Chartered Account certifying that relevant taxes have been already paid to Income Tax. Most Banks would offer these services. Compare the Fx Rate and Fees before you make a decision as to which Bank to proceed with.",
"title": ""
},
{
"docid": "263648",
"text": "On my recent visit to the bank, I was told that money coming into the NRE account can only be foreign currency and for NRO accounts, the money can come in local currency but has to be a valid source of income (e.g. rent or investments in India). Yes this is correct as per FMEA regulation in India. Now if we use 3rd party remittances like Remitly or Transferwise etc, they usually covert the foreign currency into local currency like INR and then deposit it. The remittance services are better suited for transferring funds to Normal Savings accounts of your loved ones. Most remittance services would transfer funds using a domestic clearing network [NEFT] and hence the trace that funds originated outside of India is lost. There could be some generic remittance that may have direct tie-up with some banks to do direct transfers. How can we achieve this in either NRE/NRO accounts? If not, what are the other options ? You can do a Wire Transfer [SWIFT] from US to Indian NRE account. You can also use the remittance services [if available] from Banks where you hold NRE Account. For example RemittoIndia from HDFC for an NRE account in HDFC, or Money2India from ICICI for an NRE account in ICICI or QuickRemit from SBI etc. These would preserve the history that funds originated from outside India. Similarly you can also deposit a Foreign Currency Check into Indian Bank Account. The funds would take around month or so to get credited. All other funds can be deposited in NRO account.",
"title": ""
},
{
"docid": "487890",
"text": "\"An alternative to a savings account is a money market account. Not a bank \"\"Money Market\"\" account which pays effectively the same silly rate as a savings account, but an actual Money Market investment account. You can even write checks against some Money Market investment accounts. I have several accounts worth about 13,000 each. Originally, my \"\"emergency fund\"\" was in a CD ladder. I started experimenting with two different Money market investment accounts recently. Here's my latest results: August returns on various accounts worth about $13k: - Discover Bank CD: $13.22 - Discover Bank CD: $13.27 - Discover Bank CD: $13.20 - Discover Savings: $13.18 - Credit Union \"\"Money Market\"\" Savings account: $1.80 - Fidelity Money Market Account (SPAXX): $7.35 - Vanguard Money market Account (VMFXX): $10.86 The actual account values are approximate. The Fidelity Money Market Account holds the least value, and the Credit Union account by far the most. The result of the experiment is that as the CDs mature, I'll be moving out of Discover Bank into the Vanguard Money Market account. You can put your money into more traditional equities mutual fund. The danger with them is the stock market may drop big the day before you want to make your withdrawl... and then you don't have the down payment for your house anymore. But a well chosen mutual fund will yield better. There are 3 ways a mutual fund increase in value: Here's how three of my mutual funds did in the past month... adjusted as if the accounts had started off to be worth about $13,000: Those must vary wildly month-to-month. By the way, if you look up the ticker symbols, VASGX is a Vanguard \"\"Fund of Funds\"\" -- it invests not 100% in the stock market, but 80% in the stock market and 20% in bonds. VSMGX is a 60/40 split. Interesting that VASGX grew less than VSMGX...but that assumes my spreadsheet is correct. Most of my mutual funds pay dividends and capital gains once or twice a year. I don't think any pay in August.\"",
"title": ""
},
{
"docid": "277475",
"text": "One of my friend is sending 100000 pounds to India, Although you haven't asked, this is a large amount of funds and depending on why it is, there could be taxes to you or lot of paperwork. He is asking for RIB and IBAN and I am not aware of it. India does not have IBAN. IBAN is mostly in Europe, Australia and New Zealand. You would need to give Bank Account Number and SWIFT BIC. The details can be found here. Best talk to your Branch to understand.",
"title": ""
},
{
"docid": "516756",
"text": "As you are not a tax resident in India, the income you have earned can be moved to India tax free. However if you are investing the funds into say shares / fixed deposits etc, the income you earn on these funds is taxable in India. The funds can be transferred directly into savings account. However its advisible to open an NRE/NRO account as its easier to track funds for tax purposes. i.e. these accounts by nature certify that the funds received into them are from foreign sources and can easily be explained to the tax authorities. However establishing the origin of funds in ordinary savings accounts needs more paper work. Whenever there is a scrutiny by tax authorities on this savings account, it would need more efforts to establish that the credits are from foreign earnings.",
"title": ""
},
{
"docid": "193842",
"text": "You would need to pay tax on the 10% gain. Was this money loaned from your NRE account? Is there paperwork to show that there was this loan given? If yes then it would be easy to get this back into NRE account. Once in NRE account you can move this back to US without any issue. If not, then you can get this into NRO account. From NRO account you would need to consult a CA to do some paperwork [essentially certifying that you have paid all taxes due] so that funds can be remitted outside. Edit: Looks like you have completed all formalities. A credit to NRE Account can only happen from funds outside of India. However a credit from India into NRE account can happen under some circumstances, like Loan give and received back. You would need a CA in India to help you complete the formalities. The tax is due in India as this was due to gain in India. As you are US resident for tax purposes, and US taxes global income, this is taxable in US as well. You can claim relief in US to the extent of taxes paid in India. India and US have DTAA.",
"title": ""
},
{
"docid": "271415",
"text": "As an NRI, you can't hold a regular savings account. It should have been converted to NRO. Option 1: Open NRE account : Since I am relocating permanently this might not be good option for me as converting This is the best Option as funds into NRE are not taxable in India. The provides a clean paper trail so that if there are any tax queries, you can answer them easily. You can open a Rupee NRE account, move the funds. On return move the funds into Normal Savings account and close the NRE account. This is not much of hassle. Option 2: Create NRO account: There would be taxes on the interest earned of the funds. But I am not sure of this, since I will have been moved to India permanently would I need to still pay taxes on the interest earned while I am in India? Any interest in NRO or normal savings account is taxable in India. There is no exemption. Option 3: I can transfer my funds directly to my account in India but I believe I would have to pay tax on the the funds that I transfer and that would be double taxation. Which I think would be the worst option for me. Please correct me if I am wrong. This is incorrect. Any earnings outside of India when your status is NRI, is not taxable in India. Opening an NRE account provides proper paper trail of funds. As an NRI one cannot hold normal savings account. This should have been converted into an NRO account. Although there is no penalty prescribed, its violation of FEMA regulation. I also hope you were declaring any income in India, i.e. interest etc on savings and filing returns accordingly. Option 4: I can transfer the funds to my direct relatives account. I still believe there would be tax to be paid on the interest earned of the amount. You can transfer it to your parents / siblings / etc. This would come under gift tax purview and would not be taxable. They can then gift this back to you. However such transactions would appear to be evading regulations and may come under scrutiny. Interest on Savings account is taxable. So best is go with Option 1. No hassle. Else go with Option 3, but ensure that you have all the paperwork kept handy for next 7 years.",
"title": ""
},
{
"docid": "539263",
"text": "There are times when investing in an ETF is more convenient than a mutual fund. When you invest in a mutual fund, you often have an account directly with the mutual fund company, or you have an account with a mutual fund broker. Mutual funds often have either a front end or back end load, which essentially gives you a penalty for jumping in and out of funds. ETFs are traded exactly like stocks, so there is inherently no load when buying or selling. If you have a brokerage account and you want to move funds from a stock to a mutual fund, an ETF might be more convenient. With some accounts, an ETF allows you to invest in a fund that you would not be able to invest in otherwise. For example, you might have a 401k account through your employer. You might want to invest in a Vanguard mutual fund, but Vanguard funds are not available with your 401k. If you have access to a brokerage account inside your 401k, you can invest in the Vanguard fund through the associated ETF. Another reason that you might choose an ETF over a mutual fund is if you want to try to short the fund.",
"title": ""
},
{
"docid": "13215",
"text": "\"No, you do not need an OCI card to continue to have an NRE or NRO account. You are now classified as a PIO -- Person of Indian Origin -- (and you don't need to have a PIO card issued by the Government of India to prove it) and are entitled to use NRE and NRO accounts just as you were when you were a NRI (NonResident Indian). But, you should inform the banks where you have NRE and NRO accounts that you have changed citizenship, and they may need to go through their KYC (Know Your Customer) process with you all over again. If you don't get an OCI Card, you will need to have an Indian visa stamped into your new US passport to visit India, and please do remember to send your Indian passport to the nearest Indian Consulate for cancellation. Keep the surrender certificate and cancelled passport in your safe deposit box forever; your grandchildren will need it to get visas to visit India. (My granddaughter just did). If you do get an OCI Card, you will need to have an OCI stamp put into your new US passport, and when you renew your US passport, you will need to get the new one stamped too (and pay the fee for that, of course). You cannot enter India with just an OCI Card and a US passport without the OCI stamp in it; that stamp is vital. If you move from one residential address in the US to another, you will need to get a new OCI Card issued because, unlike the US \"\"green card\"\", the OCI card has your residential address on it. Once again, a fee is involved. All these processes take many weeks because the whole paperwork has to go to the Ministry of External Affairs in New Delhi, and meanwhile, your passport is not available to you for a trip to Europe or Japan or Taiwan or China if you need to go there on business (or for pleasure).\"",
"title": ""
},
{
"docid": "450925",
"text": "How to send the full loan amount from Saudi Arabia (money exchange), because I have a money transfer limit? There is no limit for sending money into India. Just use the right banking channel and transfer the funds. If I sent to India, what about tax and all that in India? In a financial year if you are outside of India for more than 182 days, you are Non-Resident for tax purposes. Any money you earn outside of India is tax free in India. i.e. there is no tax for this funds in India. If it is possible to send the money, to whom do I have to send it (my account, or my parents account) Whatever is convenient, preferably to your own NRE/NRO account. Any documents I have to show for tax issues (in case tax) You have to establish that you are NRI and hence this funds are not taxable. Hence its best you transfer into NRE/NRO account. If you transfer to your parents account, you would need a gift deed to make this non-taxable to your parents. I have savings account my self in Axis Bank, for the past 3 years I am paying taxes, if I send to my Axis Bank account how can I withdraw the full amount (10 lakhs (1,000,000)) on single day Withdrawal is possible by cash or cheque You can write a check, do a NEFT/RTGS transfer to your loan account, you can withdraw cash by giving some notice time to the Branch Manager of your Branch.",
"title": ""
},
{
"docid": "153528",
"text": "For the financial year 1 April 2014 to 31 March 2015 as you have / will be spending more than 182 days outside of India, you are Non-Resident from tax point of view. For the period 1 April 2014 to Aug 2014, any salary / income you have earned in India is taxable and tax need to be paid. For the period Aug 2014 to 31 March 2015 the income you have earned in Saudi is not taxable in India. You can transfer money to India or keep in Saudi, it has no effect on the taxes. Any interest income you earn, or rental income you earn, or any other source of income in India is taxable. You would need to file returns accordingly. An NRE Accounts allows you to transfer funds out of India without any questions. So if you intend at some point in time in future to move funds out of India [say settling down in Saudi or UK or US etc] it is advisable to have NRE account. If you are sure you don't want to transfer funds out of India, you should open an NRO account.",
"title": ""
},
{
"docid": "417769",
"text": "How do I directly get my Freelancing amount in my Axis bank account? Do I need to inform my Bank before receiving any such payment? Yes you can get it directly into your Axis Bank Account. You would need to inform your client your Bank Account Number, Bank Name and Address and Swift BIC or IFSC Code [Axis Bank website or Branch can tell you]. You can receive credits in Euro's. Upon receipt Axis Bank will automatically convert this into Rupees using standard rate. Your Bank [Axis] may also charge some Bank fees for the wire transfer. How do I pay tax for this extra income in India? You would need to treat this as income and add it to total income including salary and calculate tax accordingly. You can pay taxes online using Income Tax India website. You can also approach a CA who would do the tax computation, paying taxes and filing returns for as little as Rs 1000 - 2000/- Edit: IBAN is International Bank Account Number. Explain to you client that India does not subscribe to IBAN. Its right now only used by Europe and Australia. Give you normal Bank Account Number. Please call up your Bank / walk into your Branch to get the SWIFT BIC. It will be something like this http://www.theswiftcodes.com/india/page/3/",
"title": ""
},
{
"docid": "449124",
"text": "In addition to all the good information that JoeTaxpayer has provided, be aware of this. When you sell mutual fund shares, you can, if you choose to do so, tell the mutual fund company which shares you want to sell (e.g. all shares purchased on xx/yy/2010 plus 10 shares out of 23.147 shares purchased on ss/tt/2011 plus...) and pay taxes on the gains/losses on those specific shares. If you do not specify which shares you want sold, the mutual fund company will tell you the gains/losses based on the average cost basis and you can use this information if you like. Note that some of your gains/losses will be short-term gains or losses if you use the average cost basis. Or, you can use the FIFO method (usually resulting in the largest gain) in which the shares are sold in the order in which they were purchased. This usually results in no short-term gains/losses. Just so that you know, most mutual fund companies will link your checking account in your bank to your account with them (a one-time paperwork deal is necessary in which your bank manager's signature is required on the authorization to be sent to the fund company). After that, the connection is nearly as seamless as with your current system. Tell the fund company you want to invest money in a certain mutual fund and to take the money from your linked checking account, and they will take care of it. Sell some shares and they will deposit the money into your linked bank account, and so on. The mutual fund company will not accept instructions from you (or someone purporting to be you) to sell shares and to send the money to Joe Blow (or to Joe Taxpayer for that matter): the proceeds of redemptions go to your checking account or are used to buy shares in other mutual funds offered by the company (called an exchange and not a redemption). Oh, and most fund companies offer automatic investments (as well as automatic redemptions) at fixed time intervals, just as with your bank.",
"title": ""
},
{
"docid": "307404",
"text": "I am a non-resident alien transferring a limited amount ( in dollars post tax) to India every couple of months. Assuming you are transferring this into an NRE account in India or atleast NRO account in India. As a NRI, by regulations one should not hold normal Savings account. This has to be converted into NRO. I put that money as a fixed deposit in a bank (which gives 6-7 percent annual return) Assuming you have FCNR deposits. Also assuming that you are declaring the taxes in your US Tax returns and paying tax accordingly. There is no tax in India on FCNR. If this was in ordinary FD or in NRO account, you are declaring and paying taxes in India as well as in US. What is the max limit on transferring money back from India to USA? If you have transferred this into NRE account, there is no limit. Other account there is a limit. Read more at Liberalized Remittance Scheme and here. What are the legitimate ways to transfer the money? From India point of view, this has to be Bank to Bank transfers. You can't carry cash [Indian Rupees] outside of India beyond Rs 25000 [or 15000?]. You can't hold excess of USD 250 without valid purpose. Western Union is not authorized to transfer funds out of India. Will there be any tax levied? No assuming you are already paying taxes on the Interest in US and depending on the type of account in India.",
"title": ""
},
{
"docid": "40682",
"text": "I was wondering if I could make part of the payment here in USD legally? Although not directly illegal ... From an India tax and FMEA point of view this would be a bit complicated. A NRI Seller cannot repatriate the proceeds from sale of house unless he had purchased this from NRE account and repatriation is only possible for original purchase amount. For the gains Seller has to apply for repatriation of funds. A NRI Seller has to pay taxes on gains and this transaction should not look like facilitating a tax fraud in case NRI Seller does not pay his taxes. As a Buyer if you make the purchase from your NRE account [i.e. Move US funds into India into NRE Account], it will ease you ability to repatriate funds in future. Depending on the property value and PAN card availability of seller, you have to deduct 1% to 30.12% tax from the value and deposit this with Income Tax India. PS: It is recommended that you consult a Professional CA to help you with modalities.",
"title": ""
},
{
"docid": "446647",
"text": "I want to send some money to Indian in my saving account but I haven't any NRO/NRE account. It is advisable to Open an NRE account. As an NRI you cannot hold a savings account. Please have this converted into NRO account ASAP. Process or Transaction charges or Tax (levied by Indian bank) on money what I'll send to my saving account in India. I know the process or transaction charges (applied by UK banks) from UK to India. There will be a nominal charge levied by banks in India. If you use dedicated Remittance services [Most Leading Indian Banks offer this], these are mostly free. Is there any limit to get rid off tax? Nope there isn't any limit. This depends on service provider. What types of paper work I'll need to do for showing that income is sent from UK after paying tax. If you transfer to NRE account. There is no paperwork required. It is implicit. If not you have to establish that the funds are received from outside India, keep copies of the transfer request initiated, debits to the Bank Account in UK, your salary slips, Passport stamps etc.",
"title": ""
},
{
"docid": "575241",
"text": "Part 1 Quite a few [or rather most] countries allow USD account. So there is no conversion. Just to illustrare; In India its allowed to have a USD account. The funds can be transfered as USD and withdrawn as USD, the interest is in USD. There no conversion at any point in time. Typically the rates for CD on USD account was Central Bank regulated rate of 5%, recently this was deregulated, and some banks offer around 7% interest. Why is the rate high on USD in India? - There is a trade deficit which means India gets less USD and has to pay More USD to buy stuff [Oil and other essential items]. - The balance is typically borrowed say from IMF or other countries etc. - Allowing Banks to offer high interest rate is one way to attract more USD into the country in short term. [because somepoint in time they may take back the USD out of India] So why isn't everyone jumping and making USD investiments in India? - The Non-Residents who eventually plan to come back have invested in USD in India. - There is a risk of regulation changes, ie if the Central Bank / Country comes up pressure for Forex Reserves, they may make it difficut to take back the USD. IE they may impose charges / taxes or force conversion on such accounts. - The KYC norms make it difficult for Indian Bank to attract US citizens [except Non Resident Indians] - Certain countries would have explicit regulations to prevent Other Nationals from investing in such products as they may lead to volatility [ie all of them suddenly pull out the funds] - There would be no insurance to foreign nationals. Part 2 The FDIC insurance is not the reason for lower rates. Most countires have similar insurance for Bank deposits for account holdes. The reason for lower interst rate is all the Goverments [China etc] park the excess funds in US Treasuries because; 1. It is safe 2. It is required for any international purchase 3. It is very liquid. Now if the US Fed started giving higher interest rates to tresaury bonds say 5%, it essentially paying more to other countries ... so its keeping the interest rates low even at 1% there are enough people [institutions / governemnts] who would keep the money with US Treasury. So the US Treasury has to make some revenue from the funds kept at it ... it lends at lower interest rates to Bank ... who in turn lend it to borrowers [both corporate and retail]. Now if they can borrow cheaply from Fed, why would they pay more to Individual Retail on CD?, they will pay less; because the lending rates are low as well. Part 3 Check out the regulations",
"title": ""
},
{
"docid": "585494",
"text": "\"Pay off the credit cards. From now on, pay off the credit cards monthly. Under no circumstances should you borrow money. You have net worth but no external income. Borrowing is useless to you. $200,000 in two bank accounts, because if one bank collapses, you want to have a spare while you wait for the government to pay off the guarantee. Keep $50,000 in checking and another $50k in savings. The remainder put into CDs. Don't expect interest income beyond inflation. Real interest rates (after inflation) are often slightly negative. People ask why you might keep money in the bank rather than stocks/bonds. The problem is that stocks/bonds don't always maintain their value, much less go up. The bank money won't gain, but it won't suddenly lose half its value either. It can easily take five years after a stock market crash for the market to recover. You don't want to be withdrawing from losses. Some people have suggested more bonds and fewer stocks. But putting some of the money in the bank is better than bonds. Bonds sometimes lose money, like stocks. Instead, park some of the money in the bank and pick a more aggressive stock/bond mixture. That way you're never desperate for money, and you can survive market dips. And the stock/bond part of the investment will return more at 70/30 than 60/40. $700,000 in stock mutual funds. $300,000 in bond mutual funds. Look for broad indexes rather than high returns. You need this to grow by the inflation rate just to keep even. That's $20,000 to $30,000 a year. Keep the balance between 70/30 and 75/25. You can move half the excess beyond inflation to your bank accounts. That's the money you have to spend each year. Don't withdraw money if you aren't keeping up with inflation. Don't try to time the market. Much better informed people with better resources will be trying to do that and failing. Play the odds instead. Keep to a consistent strategy and let the market come back to you. If you chase it, you are likely to lose money. If you don't spend money this year, you can save it for next year. Anything beyond $200,000 in the bank accounts is available for spending. In an emergency you may have to draw down the $200,000. Be careful. It's not as big a cushion as it seems, because you don't have an external income to replace it. I live in southern California but would like to move overseas after establishing stable investments. I am not the type of person that would invest in McDonald's, but would consider other less evil franchises (maybe?). These are contradictory goals, as stated. A franchise (meaning a local business of a national brand) is not a \"\"stable investment\"\". A franchise is something that you actively manage. At minimum, you have to hire someone to run the franchise. And as a general rule, they aren't as turnkey as they promise. How do you pick a good manager? How will you tell if they know how the business works? Particularly if you don't know. How will you tell that they are honest and won't just embezzle your money? Or more honestly, give you too much of the business revenues such that the business is not sustainable? Or spend so much on the business that you can't recover it as revenue? Some have suggested that you meant brand or stock rather than franchise. If so, you can ignore the last few paragraphs. I would be careful about making moral judgments about companies. McDonald's pays its workers too little. Google invades privacy. Exxon is bad for the environment. Chase collects fees from people desperate for money. Tesla relies on government subsidies. Every successful company has some way in which it can be considered \"\"evil\"\". And unsuccessful companies are evil in that they go out of business, leaving workers, customers, and investors (i.e. you!) in the lurch. Regardless, you should invest in broad index funds rather than individual stocks. If college is out of the question, then so should be stock investing. It's at least as much work and needs to be maintained. In terms of living overseas, dip your toe in first. Rent a small place for a few months. Find out how much it costs to live there. Remember to leave money for bigger expenses. You should be able to live on $20,000 or $25,000 a year now. Then you can plan on spending $35,000 a year to do it for real (including odd expenses that don't happen every month). Make sure that you have health insurance arranged. Eventually you may buy a place. If you can find one that you can afford for something like $100,000. Note that $100,000 would be low in California but sufficient even in many places in the US. Think rural, like the South or Midwest. And of course that would be more money in many countries in South America, Africa, or southern Asia. Even southern and eastern Europe might be possible. You might even pay a bit more and rent part of the property. In the US, this would be a duplex or a bed and breakfast. They may use different terms elsewhere. Given your health, do you need a maid/cook? That would lean towards something like a bed and breakfast, where the same person can clean for both you and the guests. Same with cooking, although that might be a second person (or more). Hire a bookkeeper/accountant first, as you'll want help evaluating potential purchases. Keep the business small enough that you can actively monitor it. Part of the problem here is that a million dollars sounds like a lot of money but isn't. You aren't rich. This is about bare minimum for surviving with a middle class lifestyle in the United States and other first world countries. You can't live like a tourist. It's true that many places overseas are cheaper. But many aren't (including much of Europe, Japan, Australia, New Zealand, etc.). And the ones that aren't may surprise you. And you also may find that some of the things that you personally want or need to buy are expensive elsewhere. Dabble first and commit slowly; be sure first. Include rarer things like travel in your expenses. Long term, there will be currency rate worries overseas. If you move permanently, you should certainly move your bank accounts there relatively soon (perhaps keep part of one in the US for emergencies that may bring you back). And move your investments as well. Your return may actually improve, although some of that is likely to be eaten up by inflation. A 10% return in a country with 12% inflation is a negative real return. Try to balance your investments by where your money gets spent. If you are eating imported food, put some of the investment in the place from which you are importing. That way, if exchange rates push your food costs up, they will likely increase your investments at the same time. If you are buying stuff online from US vendors and having it shipped to you, keep some of your investments in the US for the same reason. Make currency fluctuations work with you rather than against you. I don't know what your circumstances are in terms of health. If you can work, you probably should. Given twenty years, your million could grow to enough to live off securely. As is, you would be in trouble with another stock market crash. You'd have to live off the bank account money while you waited for your stocks and bonds to recover.\"",
"title": ""
},
{
"docid": "78813",
"text": "The simplest way is you transfer the funds into your NRE account in India. From the NRE account transfer the funds to your brother-in-law and show the purpose as Loan. From 2012 onwards RBI has simplified things under FMEA and your brother-in-law can deposit/repay the loan back into the NRE account. Once the funds are in NRE account you can repatriate then whenever you like. This entire process requires less paperwork. The option you have suggested is also fine, however your brother-in-law needs to engage the services of a CA and he will authenticate the purpose of remittance to the Bank. Based on this certificate the Bank will transfer the funds outside of India.",
"title": ""
},
{
"docid": "286825",
"text": "There is no difference in taxation in India if you transfer every month or bulk. If you use specialized remittance services from leading Indian Banks, there would be little difference in fees. Assuming you are keeping the funds in NRE account in India and hold it in GBP, you get a slight better rate of interest that what you would get in UK. The interest would not be taxable in India, however it would be in UK. If you convert the funds at hold it in NRE, Rupee account, you would get still better rate of interest. However you are taking the Fx risk when you try and convert this back to GBP incase you decide to stay on. There are no right or wrong answers Edit: There is no limit on the amount of funds earned as NRE that can be got into India tax free. There is a time limit of 7 Years to get the funds back to India tax free. From a tax point of view if you transfer into NRE account its easy. If you transfer into Normal Savings account you would need some paperwork.",
"title": ""
},
{
"docid": "153660",
"text": "\"For a non-ETF mutual fund, you can only buy shares of the mutual fund from the mutual fund itself (at a price that the mutual fund will reveal only at the end of the day) and can only shares back to the mutual fund (again at a price that the mutual fund will reveal only at the end of the day). There is no open market in the sense that you cannot put in a bid to buy, say, 100 shares of VFINX at $217 per share through a brokerage, and if there is a seller willing to sell 100 shares of VFINX to you at $217, then the sale is consummated and you are now the proud owner of 100 shares of VFINX. The only buyer or seller of VFINX is the mutual find itself, and you tell it that you \"\"want to buy 100 shares of VFINX and please take the money out of my checking account\"\". If this order is entered before the markets close at 4 pm, the mutual fund determines its share price as of the end of the day, opens a new account for you and puts 100 shares of VFINX in it (or adds 100 shares of VFINX to your already existing pile of shares) and takes the purchase price out of your checking account via an ACH transfer. Similarly for redeeming/selling shares of VFINX that you own (and these are held in an account at the mutual fund itself, not by your brokerage): you tell the mutual fund to that you \"\"wish to redeem 100 shares and please send the proceeds to my bank account\"\" and the mutual fund does this at the end of the day, and the money appears in your bank account via ACH transfer two or three days later. Generally, these transactions do not need to be for round lots of multiples of 100 shares for efficiency; most mutual fund will gladly sell you fractional shares down to a thousandth of a share. In contrast, shares of an exchange-traded fund (ETF) are just like stock shares in that they can be bought and sold on the open market and your broker will charge you fees for buying and selling them. Selling fractional shares on the open market is generally not possible, and trading in round lots is less expensive. Also, trades occur at all times of the stock exchange day, not just at the end of the day as with non-ETF funds, and the price can fluctuate during the day too. Many non-ETF mutual funds have an ETF equivalent: VOO is the symbol for Vanguard's S&P 500 Index ETF while VFINX is the non-ETF version of the same index fund. Read more about the differences between ETFs and mutual funds, for example, here.\"",
"title": ""
},
{
"docid": "88575",
"text": "\"A mutual fund's return or yield has nothing to do with what you receive from the mutual fund. The annual percentage return is simply the percentage increase (or decrease!) of the value of one share of the mutual fund from January 1 till December 31. The cash value of any distributions (dividend income, short-term capital gains, long-term capital gains) might be reported separately or might be included in the annual return. What you receive from the mutual fund is the distributions which you have the option of taking in cash (and spending on whatever you like, or investing elsewhere) or of re-investing into the fund without ever actually touching the money. Regardless of whether you take a distribution as cash or re-invest it in the mutual fund, that amount is taxable income in most jurisdictions. In the US, long-term capital gains are taxed at different (lower) rates than ordinary income, and I believe that long-term capital gains from mutual funds are not taxed at all in India. You are not taxed on the increase in the value of your investment caused by an increase in the share price over the year nor do you get deduct the \"\"loss\"\" if the share price declined over the year. It is only when you sell the mutual fund shares (back to the mutual fund company) that you have to pay taxes on the capital gains (if you sold for a higher price) or deduct the capital loss (if you sold for a lower price) than the purchase price of the shares. Be aware that different shares in the sale might have different purchase prices because they were bought at different times, and thus have different gains and losses. So, how do you calculate your personal return from the mutual fund investment? If you have a money management program or a spreadsheet program, it can calculate your return for you. If you have online access to your mutual fund account on its website, it will most likely have a tool called something like \"\"Personal rate of return\"\" and this will provide you with the same calculations without your having to type in all the data by hand. Finally, If you want to do it personally by hand, I am sure that someone will soon post an answer writing out the gory details.\"",
"title": ""
},
{
"docid": "183898",
"text": "It is true that this is possible, however, it's very remote in the case of the large and reputable fund companies such as Vanguard. FDIC insurance protects against precisely this for bank accounts, but mutual funds and ETFs do not have an equivalent to FDIC insurance. One thing that does help you in the case of a mutual fund or ETF is that you indirectly (through the fund) own actual assets. In a cash account at a bank, you have a promise from the bank to pay, and then the bank can go off and use your money to make loans. You don't in any sense own the bank's loans. With a fund, the fund company cannot (legally) take your money out of the fund, except to pay the expense ratio. They have to use your money to buy stocks, bonds, or whatever the fund invests in. Those assets are then owned by the fund. Legally, a mutual fund is a special kind of company defined in the Investment Company Act of 1940, and is a separate company from the investment advisor (such as Vanguard): http://www.sec.gov/answers/mfinvco.htm Funds have their own boards, and in principle a fund board can even fire the company advising the fund, though this is not likely since boards aren't usually independent. (a quick google found this article for more, maybe someone can find a better one: http://www.marketwatch.com/story/mutual-fund-independent-board-rule-all-but-dead) If Vanguard goes under, the funds could continue to exist and get a new adviser, or could be liquidated with investors receiving whatever the assets are worth. Of course, all this legal stuff doesn't help you with outright fraud. If a fund's adviser says it bought the S&P 500, but really some guy bought himself a yacht, Madoff-style, then you have a problem. But a huge well-known ETF has auditors, tons of different employees, lots of brokerage and exchange traffic, etc. so to me at least it's tough to imagine a risk here. With a small fund company with just a few people - and there are lots of these! - then there's more risk, and you'd want to carefully look at what independent agent holds their assets, who their auditors are, and so forth. With regular mutual funds (not ETFs) there are more issues with diversifying across fund companies: With ETFs, there probably isn't much downside to diversifying since you could buy them all from one brokerage account. Maybe it even happens naturally if you pick the best ETFs you can find. Personally, I would just pick the best ETFs and not worry about advisor diversity. Update: maybe also deserving a mention are exchange-traded notes (ETNs). An ETN's legal structure is more like the bank account, minus the FDIC insurance of course. It's an IOU from the company that runs the ETN, where they promise to pay back the value of some index. There's no investment company as with a fund, and therefore you don't own a share of any actual assets. If the ETN's sponsor went bankrupt, you would indeed have a problem, much more so than if an ETF's sponsor went bankrupt.",
"title": ""
}
] |
8680
|
What to do with small dividends in brokerage account?
|
[
{
"docid": "128571",
"text": "Don't sit on it, because the money does not work for you. Add more money to it and buy a stock or stocks of the company.",
"title": ""
},
{
"docid": "102442",
"text": "Some brokerages will allow you to enroll your account in a dividend reinvestment plan -- TD Ameritrade and I think Schwab for example. The way the plan works is that they would take your $4 and give you whatever fractional share of the ETF it is worth on the payment date. There are no fees associated with this purchase (or at least there are in the programs I've seen -- if you have to pay a fee, look for another brokerage). You may also be able to enroll specific securities instead of the entire account into dividend reinvestment. Call your brokerage to see what they offer.",
"title": ""
},
{
"docid": "234039",
"text": "Assuming you have no new cash to add to your account as gyurisc has suggested, I wouldn't sweat the small amounts – it doesn't hurt to have a little cash sit idle, even if you want to theoretically be fully invested (the wisdom of doing that, or not, perhaps worthy of another question :-) If you try too hard to invest the small amounts frequently, you're likely to get killed on fees. My strategy (if you could call it that) is to simply let small amounts accumulate until there's enough to buy more shares without paying too much commission. For instance, I don't like fees to be more than 1% of the shares purchased, so with a $10 commission per trade, I prefer to make minimum $1000 purchases. I used to roll small amounts of cash into a no-load money market fund I could buy without commission, and then purchase shares when I hit the threshold, but even putting the cash in a money market fund isn't worth the hassle today with rates of return from money market funds being close to zero.",
"title": ""
}
] |
[
{
"docid": "225162",
"text": "Assuming a USA taxable account: Withdrawing funds from a brokerage account has nothing to do with taxes. Taxes are owed on the profit when you sell a stock, no matter what you do with the funds. Taxes are owed on any dividends the stock produces, no matter what you do with the dividend. The brokerage sends you a form 1099 each year that shows the amounts of dividends and profits. You have to figure out the taxes from that.",
"title": ""
},
{
"docid": "360716",
"text": "\"What you seem to want is a dividend reinvestment plan (DRIP). That's typically offered by the broker, not by the ETF itself. Essentially this is a discounted purchase of new shares when you're dividend comes out. As noted in the answer by JoeTaxpayer, you'll still need to pay tax on the dividend, but that probably won't be a big problem unless you've got a lot of dividends. You'll pay that out of some other funds when it's due. All DRIPs (not just for ETFs) have potential to complicate computation of your tax basis for eventual sale, so be aware of that. It doesn't have to be a show-stopper for you, but it's something to consider before you start. It's probably less of a problem now than it used to be since brokers now have to report your basis on the 1099-B in the year of sale, reducing your administrative burden (if you trust them to get it right). Here's a list of brokerages that were offering this from a top-of-the-search-list article that I found online: Some brokerages, including TD Ameritrade, Vanguard, Scottrade, Schwab and, to a lesser extent, Etrade, offer ETF DRIPs—no-cost dividend reinvestment programs. This is very helpful for busy clients. Other brokerages, such as Fidelity, leave ETF dividend reinvestment to their clients. Source: http://www.etf.com/sections/blog/23595-your-etf-has-drip-drag.html?nopaging=1 Presumably the list is not constant. I almost didn't included but I thought the wide availability (at least as of the time of the article's posting) was more interesting than any specific broker on it. You'll want to do some research before you choose a broker to do this. Compare fees for sure, but also take into account other factors like how soon after the dividend they do the purchase (is it the ex-date, the pay date, or something else?). A quick search online should net you several decent articles with more information. I just searched on \"\"ETF DRIP\"\" to check it out.\"",
"title": ""
},
{
"docid": "148141",
"text": "\"In essence the problem that the OP identified is not that the FX market itself has poor liquidity but that retail FX brokerage sometimes have poor counterparty risk management. The problem is the actual business model that many FX brokerages have. Most FX brokerages are themselves customers of much larger money center banks that are very well capitalized and provide ample liquidity. By liquidity I mean the ability to put on a position of relatively decent size (long EURUSD say) at any particular time with a small price impact relative to where it is trading. For spot FX, intraday bid/ask spreads are extremely small, on the order of fractions of pips for majors (EUR/USD/GBP/JPY/CHF). Even in extremely volatile situations it rarely becomes much larger than a few pips for positions of 1 to 10 Million USD equivalent notional value in the institutional market. Given that retail traders rarely trade that large a position, the FX spot market is essentially very liquid in that respect. The problem is that there are retail brokerages whose business model is to encourage excessive trading in the hopes of capturing that spread, but not guaranteeing that it has enough capital to always meet all client obligations. What does get retail traders in trouble is that most are unaware that they are not actually trading on an exchange like with stocks. Every bid and ask they see on the screen the moment they execute a trade is done against that FX brokerage, and not some other trader in a transparent central limit order book. This has some deep implications. One is the nifty attribute that you rarely pay \"\"commission\"\" to do FX trades unlike in stock trading. Why? Because they build that cost into the quotes they give you. In sleepy markets, buyers and sellers cancel out, they just \"\"capture\"\" that spread which is the desired outcome when that business model functions well. There are two situations where the brokerage's might lose money and capital becomes very important. In extremely volatile markets, every one of their clients may want to sell for some reason, this forces the FX brokers to accumulate a large position in the opposite side that they have to offload. They will trade in the institutional market with other brokerages to net out their positions so that they are as close to flat as possible. In the process, since bid/ask spreads in the institutional market is tighter than within their own brokerage by design, they should still make money while not taking much risk. However, if they are not fast enough, or if they do not have enough capital, the brokerage's position might move against them too quickly which may cause them lose all their capital and go belly up. The brokerage is net flat, but there are huge offsetting positions amongst its clients. In the example of the Swiss Franc revaluation in early 2015, a sudden pop of 10-20% would have effectively meant that money in client accounts that were on the wrong side of the trade could not cover those on the other side. When this happens, it is theoretically the brokerage's job to close out these positions before it wipes out the value of the client accounts, however it would have been impossible to do so since there were no prices in between the instantaneous pop in which the brokerage could have terminated their client's losing positions, and offload the risk in the institutional market. Since it's extremely hard to ask for more money than exist in the client accounts, those with strong capital positions simply ate the loss (such as Oanda), those that fared worse went belly up. The irony here is that the more leverage the brokerage gave to their clients, the less money would have been available to cover losses in such an event. Using an example to illustrate: say client A is long 1 contract at $100 and client B is short 1 contract at $100. The brokerage is thus net flat. If the brokerage had given 10:1 leverage, then there would be $10 in each client's account. Now instantaneously market moves down $10. Client A loses $10 and client B is up $10. Brokerage simply closes client A's position, gives $10 to client B. The brokerage is still long against client B however, so now it has to go into the institutional market to be short 1 contract at $90. The brokerage again is net flat, and no money actually goes in or out of the firm. Had the brokerage given 50:1 leverage however, client A only has $2 in the account. This would cause the brokerage close client A's position. The brokerage is still long against client B, but has only $2 and would have to \"\"eat the loss\"\" for $8 to honor client B's position, and if it could not do that, then it technically became insolvent since it owes more money to its clients than it has in assets. This is exactly the reason there have been regulations in the US to limit the amount of leverage FX brokerages are allowed to offer to clients, to assure the brokerage has enough capital to pay what is owed to clients.\"",
"title": ""
},
{
"docid": "173088",
"text": "\"What is a stock? A share of stock represents ownership of a portion of a corporation. In olden times, you would get a physical stock certificate (looking something like this) with your name and the number of shares on it. That certificate was the document demonstrating your ownership. Today, physical stock certificates are quite uncommon (to the point that a number of companies don't issue them anymore). While a one-share certificate can be a neat memento, certificates are a pain for investors, as they have to be stored safely and you'd have to go through a whole annoying process to redeem them when you wanted to sell your investment. Now, you'll usually hold stock through a brokerage account, and your holdings will just be records in a database somewhere. You'll pick a broker (more on that in the next question), instruct them to buy something, and they'll keep track of it in your account. Where do I get a stock? You'll generally choose a broker and open an account. You can read reviews to compare different brokerages in your country, as they'll have different fees and pricing. You can also make sure the brokerage firm you choose is in good standing with the financial regulators in your country, though one from a major national bank won't be unsafe. You will be required to provide personal information, as you are opening a financial account. The information should be similar to that required to open a bank account. You'll also need to get your money in and out of the account, so you'll likely set up a bank transfer. It may be possible to request a paper stock certificate, but don't be surprised if you're told this is unavailable. If you do get a paper certificate, you'll have to deal with considerably more hassle and delay if you want to sell later. Brokers charge a commission, which is a fee per trade. Let's say the commission is $10/trade. If you buy 5 shares of Google at $739/share, you'd pay $739 * 5 + $10 = $3705 and wind up with $3695 worth of stock in your account. You'd pay the same commission when you sell the stock. Can anyone buy/own/use a stock? Pretty much. A brokerage is going to require that you be a legal adult to maintain an account with them. There are generally ways in which a parent can open an account on behalf of an underage child though. There can be different types of restrictions when it comes to investing in companies that are not publicly held, but that's not something you need to worry about. Stocks available on the public stock market are available to, well, the public. How are stocks taxed? Taxes differ from country to country, but as a general rule, you do have to provide the tax authorities with sufficient information to determine what you owe. This means figuring out how much you purchased the stock for and comparing that with how much you sold it for to determine your gain or loss. In the US (and I suspect in many other countries), your brokerage will produce an annual report with at least some of this information and send it to the tax authorities and you. You or someone you hire to do your taxes will use that report to compute the amount of tax owed. Your brokerage will generally keep track of your \"\"cost basis\"\" (how much you bought it for) for you, though it's a good idea to keep records. If you refuse to tell the government your cost basis, they can always assume it's $0, and then you'll pay more tax than you owe. Finding the cost basis for old investments can be difficult many years later if the records are lost. If you can determine when the stock was purchased, even approximately, it's possible to look back at historical price data to determine the cost. If your stock pays a dividend (a certain amount of money per-share that a company may pay out of its profits to its investors), you'll generally need to pay tax on that income. In the US, the tax rate on dividends may be the same or less than the tax rate on normal wage income depending on how long you've held the investment and other rules.\"",
"title": ""
},
{
"docid": "250559",
"text": "\"This is why California tax code is even more messed up than the Federal - they take the Federal and then add some. Or remove. Or mix up. Whether your brokerage will send 1099 or not is up to the brokerage. Its a Federal requirement. California may require them to send it out for CA residents, or may not. They may adhere to the FTB, or may not. It doesn't matter to you. You'll have to keep track of the interest and dividends received, cost basis for the securities, etc etc., just as any other brokerage account. You cannot rely solely on the information on the 1099 anyway, since it doesn't include many things you have to take into account for your Federal tax return as well, wash sales (inter-brokerage) being the most obvious example. As to what happens when you're 65 - you'll have to keep track, again, of all the taxes paid, and track your California basis in the account, and your Federal basis in the account, and they will not be the same. Reconciliation time again when you get there. What a mess. If you move to another state - the taxes you paid to CA are \"\"lost\"\". Similarly, if you move in to California, all the gains prior to moving in are not taxed by California. Whatever happens after - is taxed by CA as if it was a regular investment account.\"",
"title": ""
},
{
"docid": "263088",
"text": "Keep in mind the ex-dividend date is different from the payable date (the day the dividend is paid). That means the market price will already have adjusted lower due to the dividend. Short answer: you get the lower price when reinvesting. So here's Vanguard's policy, it should be similar to most brokers: When reinvesting dividends, Vanguard Brokerage Services combines the cash distributions from the accounts of all clients who have requested reinvestment in the same security, and then uses that combined total to purchase additional shares of the security in the open market. Vanguard Brokerage will attempt to purchase the reinvestment shares by entering a market order at the market opening on the payable date. The new shares are divided proportionately among the clients' accounts, in whole and fractional shares rounded to three decimal places. If the total purchase can't be completed in one trade, clients will receive shares purchased at the weighted average price paid by Vanguard Brokerage Services.",
"title": ""
},
{
"docid": "266457",
"text": "TL; DR version of my answer: In view of your age and the fact that you have just opened a Roth IRA account with Vanguard, choose the Reinvest Dividend and Capital Gains distributions option. If Vanguard is offering an option of having earnings put into a money market settlement account, it might be that you have opened your Roth IRA account with Vanguard's brokerage firm. Are you doing things like investing your Roth money into CDs or bonds (including zero-coupon or STRIP bonds) or individual stocks? If so, then the money market settlement account (might be VMMXX, the Vanguard Prime Money Market Fund) within the Roth IRA account is where all the money earned as interest on the CDs or bonds, dividends from the stocks, and the proceeds (including any resulting capital gains) from the sales of any of these will go. You can then decide where to invest that money (all within the Roth IRA). Leaving the money in the settlement account for a long time is not a good idea even if you are just accumulating the money so as to be able to buy 100 shares of APPL or GOOG at some time in the future. Put it into a CD in your Roth IRA brokerage account while you wait. If your Roth IRA is invested only in Vanguard's mutual funds and is likely to remain so in the foreseeable future, then you don't really need an account with their brokerage. You can still use a money market settlement fund to transfer money between various mutual fund investments within the Roth IRA account, but it really is adding an extra layer of money movement where it is not really necessary. You can sell one Vanguard mutual fund and invest the proceeds into another Vanguard mutual fund or even into several Vanguard funds without needing to have the funds transit through a money market account. Vanguard calls such a transaction an Exchange on their site. And, of course, you can just choose to reinvest all the dividends and capital gains distributions made by a mutual fund into the fund itself. Mutual funds allow purchases of fractional shares (down to three or even four decimal places) instead of insisting on integer numbers of shares let alone round lots of 100 shares. All this, of course, within the Roth IRA.",
"title": ""
},
{
"docid": "188232",
"text": "\"Isn't it true that on the ex-dividend date, the price of the stock goes down roughly the amount of the dividend? That is, what you gain in dividend, you lose in price drop. Yes and No. It Depends! Generally stocks move up and down during the market, and become more volatile on some news. So One can't truly measure if the stock has gone down by the extent of dividend as one cannot isolate other factors for what is a normal share movement. There are time when the prices infact moves up. Now would it have moved more if there was no dividend is speculative. Secondly the dividends are very small percentage compared to the shares trading price. Generally even if 100% dividend are announced, they are on the share capital. On share prices dividends would be less than 1%. Hence it becomes more difficult to measure the movement of stock. Note if the dividend is greater than a said percentage, there are rules that give guidelines to factor this in options and other area etc. Lets not mix these exceptions. Why is everyone making a big deal out of the amount that companies pay in dividends then? Why do some people call themselves \"\"dividend investors\"\"? It doesn't seem to make much sense. There are some set of investors who are passive. i.e. they want to invest in good stock, but don't want to sell it; i.e. more like keep it for long time. At the same time they want some cash potentially to spend; similar to interest received on Bank Deposits. This class of share holders, it makes sense to invest into companies that give dividends, as year on year they keep receiving some money. If they on the other hand has invested into a company that does not give dividends, they would have to sell some units to get the same money back. This is the catch. They have to sell in whole units, there is brokerage, fees, etc, there are tax events. Some countries have taxes that are more friendly to dividends than capital gains. Thus its an individual choice whether to invest into companies that give good dividends or into companies that don't give dividends. Giving or not giving dividends does not make a company good or bad.\"",
"title": ""
},
{
"docid": "403701",
"text": "This is really an extended comment on the last paragraph of @BenMiller's answer. When (the manager of) a mutual fund sells securities that the fund holds for a profit, or receives dividends (stock dividends, bond interest, etc.), the fund has the option of paying taxes on that money (at corporate rates) and distributing the rest to shareholders in the fund, or passing on the entire amount (categorized as dividends, qualified dividends, net short-term capital gains, and net long-term capital gains) to the shareholders who then pay taxes on the money that they receive at their own respective tax rates. (If the net gains are negative, i.e. losses, they are not passed on to the shareholders. See the last paragraph below). A shareholder doesn't have to reinvest the distribution amount into the mutual fund: the option of receiving the money as cash always exists, as does the option of investing the distribution into a different mutual fund in the same family, e.g. invest the distributions from Vanguard's S&P 500 Index Fund into Vanguard's Total Bond Index Fund (and/or vice versa). This last can be done without needing a brokerage account, but doing it across fund families will require the money to transit through a brokerage account or a personal account. Such cross-transfers can be helpful in reducing the amounts of money being transferred in re-balancing asset allocations as is recommended be done once or twice a year. Those investing in load funds instead of no-load funds should keep in mind that several load funds waive the load for re-investment of distributions but some funds don't: the sales charge for the reinvestment is pure profit for the fund if the fund was purchased directly or passed on to the brokerage if the fund was purchased through a brokerage account. As Ben points out, a shareholder in a mutual fund must pay taxes (in the appropriate categories) on the distributions from the fund even though no actual cash has been received because the entire distribution has been reinvested. It is worth keeping in mind that when the mutual fund declares a distribution (say $1.22 a share), the Net Asset Value per share drops by the same amount (assuming no change in the prices of the securities that the fund holds) and the new shares issued are at this lower price. That is, there is no change in the value of the investment: if you had $10,000 in the fund the day before the distribution was declared, you still have $10,000 after the distribution is declared but you own more shares in the fund than you had previously. (In actuality, the new shares appear in your account a couple of days later, not immediately when the distribution is declared). In short, a distribution from a mutual fund that is re-invested leads to no change in your net assets, but does increase your tax liability. Ditto for a distribution that is taken as cash or re-invested elsewhere. As a final remark, net capital losses inside a mutual fund are not distributed to shareholders but are retained within the fund to be written off against future capital gains. See also this previous answer or this one.",
"title": ""
},
{
"docid": "66626",
"text": "\"I recommend a Roth IRA. At your age you could turn 25K into a million and never pay taxes on these earnings. Of course there are yearly limits (5.5k) on the amount your can contribute to a Roth IRA account. If you haven't filed your taxes this year yet ... you can contribute 5.5K for last year and 5.5K for this year. Open two accounts at a discount brokerage firm. Trades should be about $10 or less per. Account one ... Roth IRA. Account two a brokerage account for the excess funds that can't be placed in the Roth IRA. Each year it will be easy transfer money into the Roth from this account. Be aware that you can't transfer stocks from brokerage acct to Roth IRA ... only cash. You can sell some stocks in brokerage and turn that into cash to transfer. This means settling up with the IRS on any gains/losses on that sale. Given your situation you'd likely have new cash to bring to table for the Roth IRA anyway. Invest in stocks and hold them for the long term. Do a google search for \"\"motley fool stock advisor\"\" and join. This is a premium service that picks two stocks to invest in each month. Invest small amounts (say $750) in each stock that they say you should buy. They will also tell you when to sell. They also give insights into why they selected the stock and why they are selling (aka learning experience). They pick quality companies. So if the economy is down you will still own a quality company that will make it through the storm. Avoid the temptation to load up on one stock. Follow the small amount rule mentioned above per stock. Good luck, and get in the market.\"",
"title": ""
},
{
"docid": "578619",
"text": "\"It has little to do with money or finance. It's basic neuroscience. When we get money, our brains release dopamine (read Your Money and Your Brain), and receiving dividends is \"\"getting money.\"\" It feels good, so we're more likely to do it again. What you often see are rationalizations because the above explanation sounds ... irrational, so many people want to make their behavior look more rational. Ceteris paribus a solid growth stock is as good as a solid company that pays dividends. In value-investing terms, dividend paying stocks may appear to give you an advantage in that you can keep the dividends in cash and buy when the price of the security is low (\"\"underpriced\"\"). However, as you realize, you could just sell the growth stock at certain prices and the effect would be the same, assuming you're using a free brokerage like Robin Hood. You can easily sell just a portion of the shares periodically to get a \"\"stream of cash\"\" like dividends. That presents no problem whatsoever, so this cannot be the explanation to why some people think it is \"\"smart\"\" to be a dividend investor. Yes, if you're using a brokerage like Robin Hood (there may be others, but I think this is the only one right now), then you are right on.\"",
"title": ""
},
{
"docid": "488015",
"text": "\"IMHO It is definitively not too early to start learning and thinking about personal finances and also about investing. If you like to try stock market games, make sure to use one that includes a realistic fee structure simulation as well - otherwise there'll be a very unpleasant awakening when switching to reality... I'd like to stress the need for low fees with the brokerage account! Sit down and calculate how much fees different brokers take for a \"\"portfolio\"\" of say, 1 ETF, 1 bond, 1 share of about $500 or $1000 each (e.g. order fee, annual fee, fee for paying out interest/dividend). In my experience, it is good if you can manage to make the first small investing steps before starting your career. Real jobs tend to need lots of time (particularly at the beginning), so time to learn investing is extremely scarce right at the time when you for the first time in your life earn money that could/should be invested. I'm talking of very slowly starting with a single purchase of say an ETF, a single bond next time you have saved up a suitable amount of toy money, then maybe a single share (and essentially not doing anything with them in order to avoid further fees). While such a \"\"portfolio\"\" is terrible with respect to diversification and relative fees*, this gives you the possibility to learn the procedures, to see how the fees cut in, what to do wrt taxes etc. This is why I speak about toy money and why I consider this money an investment in education. * An order fee of, say, $10 on a $500 position are terrible 4% (2 x $10) for buying + selling - depending on your local taxes, that would be several years of dividend yield for say some arbitrary Dow Jones ETF. Nevertheless, purchase + sale together are less than 3 cinema tickets.\"",
"title": ""
},
{
"docid": "155677",
"text": "That is a loaded question but I'll give it a shot. First things first you need to determine if you are ready to invest in stocks. If you have a lot of high interest debt you would be much better served paying that off before investing in stocks. Stocks return around 8%-10% in the long run, so you'd be better off paying off any debt you have that is higher than 8%-10%. Most people get their start investing in stocks through mutual funds in their 401k or a Roth IRA. If you want to invest in individual stocks instead of mutual funds then you will need to do a lot of reading and learning. You will need a brokerage account or if you have a stock in mind they might have a dividend reinvestment plan (DRIP) that you could invest in directly with the company. You will have to compare the different brokerage firms to determine which is best for you. Since you seem to be internet savvy, I suggest you use a discount brokerage that let's you buy stocks online with cheaper commissions. A good rule of thumb is to keep commissions below 1% of the amount invested. Once you have your online brokerage account open with money in there the process of actually buying the stock is fairly straightforward. Just place an order for the amount of shares you want. That order can be a market order which means the purchase will occur at the current market price. Or you can use a limit order where you control at what price your purchase will occur. There are lots of good books out there for beginners. Personally I learned from the Motley Fool. And last but not least is to have fun with it. Learn as much as you can and welcome to the club.",
"title": ""
},
{
"docid": "492053",
"text": "\"Taxes are triggered when you sell the individual stock. The IRS doesn't care which of your accounts the money is in. They view all your bank and brokerage accounts as if they are one big account mashed together. That kind of lumping is standard accounting practice for businesses. P/L, balance sheets, cash flow statements etc. will clump cash accounts as \"\"cash\"\". Taxes are also triggered when they pay you a dividend. That's why ETFs are preferable to mutual funds; ETFs automatically fold the dividends back into the ETF's value, so it doesn't cause a taxable event. Less paperwork. None of the above applies to retirement accounts. They are special. You don't report activity inside retirement accounts, because it would be very hard for regular folk to do that reporting, so that would discourage them from taking IRAs. Taxes are paid at withdrawal time (or in Roth's, never.)\"",
"title": ""
},
{
"docid": "526259",
"text": "Good question, here are some possible answers: Its a Good Idea There is probably some validity to the statictics and having money invested, generally speaking, has proven far more valuable than having it sit in a savings account. It tends to reinforce strength Suppose you own two stocks, one that is a great performer, and one that isn't. Generally speaking the high performer will pay out more, and if you reinvest more into that stock, you will be wealthier if you contributed equally to both stocks. You might forget People tend to forget to do things that are not in the forefront, and reinvestment is one of those things that slip people's mind. One of the wealth building tools that people universally recommend is automation. Reinvesting is a way to automate one aspect of one's financial life. You might spend it on something else If you put the dividends into your checking account, there is a non-zero chance that it might get put towards something else. Better to have it out of sight and mind and invested. They make money Generally speaking, the more money you have in a brokerage account, the more the brokerage makes. So it is good for them, as well as yourself. While there is some attraction to being able to see a balance that is the result of dividend investments, its just far better to have them be poured right back into whatever investment seem appropriate.",
"title": ""
},
{
"docid": "353337",
"text": "\"Whoa. These things are on two dimensions. It's like burger and fries, you can also have chicken sandwich and fries, or burger and onion rings. You can invest in an taxable brokerage account and/or an IRA. And then, within each of those... You can buy index funds and/or anything else. All 4 combinations are possible. If someone says otherwise, take your money and run. They are a shady financial \"\"advisor\"\" who is ripping you off by steering you only into products where they get a commission. Those products are more expensive because the commission comes out of your end. Not to mention any names. E.J. If you want financial advice that is honest, find a financial advisor who you pay for his advice, and who doesn't sell products at all. Or, just ask here. But I would start by listening to Suze Orman, Dave Ramsey, whomever you prefer. And read John Bogle's book. They can tell you all about the difference between money market, bonds, stocks, managed mutual funds (ripoff!) and index funds. IRA accounts, Roth IRA accounts and taxable accounts are all brokerage accounts. Within them, you can buy any security you want, including index funds. The difference is taxation. Suppose you earn $1000 and choose to invest it however Later you withdraw it and it has grown to $3000. Investing in a taxable account, you pay normal income tax on the $1000. When you later withdraw the $3000, you pay a tax on $2000 of income. If you invested more than a year, it is taxed at a much lower \"\"capital gains\"\" tax rate. With a traditional IRA account, you pay zero taxes on the initial $1000. Later, when you take the money out, you pay normal income tax on the full $3000. If you withdrew it before age 59-1/2, you also pay a 10% penalty ($300). With a Roth IRA account, you pay normal income tax on the $1000. When you withdraw the $3000 later, you pay NOTHING in taxes. Provided you followed the rules. You can invest in almost anything inside these accounts: Money market funds. Terrible return. You won't keep up with the market. Bonds. Low return but usually quite safe. Individual stocks. Good luck. Managed mutual funds. You're paying some genius stock picker to select high performing stocks. He has a huge staff of researchers and good social connections. He also charges you 1.5% per year overhead as an \"\"expense ratio\"\", which is a total loss to you. The fact is, he can usually pick stocks better than a monkey throwing darts. But he's not 1.5% better! Index funds. These just shrug and buy every stock on the market. There's no huge staff or genius manager, just some intern making small adjustments every week. As such, the expense ratio is extremely small, like 0.1%. If any of these investments pay dividends, you must pay taxes on them when they're issued, if you're not in an IRA account. This problem gets fixed in ETF's. Index ETF's. These are index funds packaged to behave like stocks. Dividends increase your stock's value instead of being paid out to you, which simplifies your taxes. If you buy index funds outside of an IRA, use these. Too many other options to get into here.\"",
"title": ""
},
{
"docid": "217472",
"text": "As you own a company, you need to know what your role is. You can never just move money into or out of the company, you have to identify the role in which you are doing it, and do it properly. There is Company, and there is You, in three different roles. You are the sole shareholder and director of Company. You are the sole employee of Company. You are also just a private person. You need to keep these three roles separate. As the sole shareholder, you own the company. However, you don't own any assets of the company. The company is yours, but the money in its bank account isn't. As a private person, you give a loan to your company. You write on a sheet of paper that You personally, give a loan to the company, how much a loan is, what interest is paid, and when the loan will be paid back (that could be 'whenever You demands the money paid back'). Then you move the money from your private bank account to the company bank account, and the company has the money it needs to fund its operation. Assume it wasn't you who loaned the money, but I gave the loan to the company. You can imagine that I would have this loan written down and signed before I hand over the cash. And you must have exactly the same papers that I would have. How do you get money from the company? The company can pay back your loan. That should be written down again, in the same way as the loan itself was written down. Other than that, there are three ways how you can get money out of the company: The company can pay You, in your role as its employee, a salary, which it can deduct from its profits. The company can pay money into a pension of the company director (that's You in your role as company director) up to £40,000 or so a year; that money is deducted from its profits again. The company pays 20% tax on its remaining profits. Then the company can pay You, in your role as company director, a dividend, usually twice a year. Each of these payments has to be written down and given to HMRC properly. Best by far to use an accountant to do all the paper work for you and advice you what to do. You can lose a lot of money by just not getting the paperwork right, by filing late etc., which the accountant will get right. The accountant will also tell you what are the optimal amounts for salary and dividend (best is a small salary, about £10,000 a year, dividend of about £30,000 a year, pension as much as the company can afford, which is then all tax free to you). You can't pay more dividend then the company can afford (paying a dividend and then not being able to pay your suppliers is criminal), and if you want higher dividends, then you will have to pay taxes on them.",
"title": ""
},
{
"docid": "477588",
"text": "\"Yes, if it's an American style option. American style options may be exercised at any time prior to expiration (even if they're not in-the-money). Generally, you are required to deliver or accept delivery of the underlying by the beginning of the next trading day. If you are short, you may be chosen by the clearinghouse to fulfill the exercise (a process called \"\"assignment\"\"). Because the clearinghouse is the counter-party to every options trade, you can be assigned even if the specific person who purchased the option you wrote didn't exercise, but someone else who holds a long position did. Similarly, you might not be assigned if that person did exercise. The clearinghouse randomly chooses a brokerage to fulfill an assignment, and the brokerage will randomly choose an individual account. If you're going to be writing options, especially using spreads, you need to have a plan ahead of time on what to do if one of your legs gets assigned. This is more likely to happen just before a dividend payment, if the payment is more than the remaining time value.\"",
"title": ""
},
{
"docid": "397976",
"text": "You are suggesting something called dollar cost averaging (or its cousin, dollar value averaging) - http://www.investopedia.com/articles/stocks/07/dcavsva.asp This is certainly a valid investment strategy, although personally, I feel that for long term investment, it is not necessary unless you plan on being an active trader. I still strongly encourage you to research these two methods and see if they would work well for your personal investment strategy and goals. As far as what sorts of investments for a taxable account, I have three general recommendations: As far as which company to use for your brokerage, I personally have accounts at Voya, TRowe Price and Fidelity. I would strongly recommend Fidelity out of those three, mostly due to customer service and quality and ease of use of their website. Vanguard is a great brokerage, but you don't have to choose them just because you plan to mostly invest in Vanguard funds. I also recommend you research how capital gains and dividend taxing works (and things like lost harvesting), so that you can structure your investments with taxes in mind. Do this ahead of time, don't wait until April of 2016 because it will be too late to save on taxes by then.",
"title": ""
},
{
"docid": "461018",
"text": "stocks represent ownership in a company. their price can go up or down depending on how much profit the company makes (or is expected to make). stocks owners are sometimes paid money by the company if the company has extra cash. these payments are called dividends. bonds represent a debt that a company owes. when you buy a bond, then the company owes that debt to you. typically, the company will pay a small amount of money on a regular basis to the bond owner, then a large lump some at some point in the future. assuming the company does not file bankrupcy, and you keep the bond until it becomes worthless, then you know exactly how much money you will get from buying a bond. because bonds have a fixed payout (assuming no bankrupcy), they tend to have lower average returns. on the other hand, while stocks have a higher average return, some stocks never return any money. in the usa, stocks and bonds can be purchased through a brokerage account. examples are etrade, tradeking, or robinhood.com. before purchasing stocks or bonds, you should probably learn a great deal more about other investment concepts such as: diversification, volatility, interest rates, inflation risk, capital gains taxes, (in the usa: ira's, 401k's, the mortgage interest deduction). at the very least, you will need to decide if you want to buy stocks inside an ira or in a regular brokerage account. you will also probably want to buy a low-expense ration etf (e.g. an index fund etf) unless you feel confident in some other choice.",
"title": ""
},
{
"docid": "595796",
"text": "The Brokerage firm will purchase shares for the dividend paid in a omnibus account for the security of the issuer and then they will distribute fractional shares among all their clients that chose Div Reinvest. They will only have to buy 1 extra share to account for the fractional portion of what they allocate. The structure of the market does not permit trading of fractional shares. There is generally not any impact to the market place for Div Reinvest with the exception of certain securities that pay large dividends that are not liquid. sometimes this occurs in preferred securities where a large amount of Div reinvestment could create a large market order that has market impact. Most brokers place market orders for the opening on the day following the payment of the dividend. When you sell the fractional portion same process as full shares are sold into the market and the fractional if traded between you and the brokers omnibus account. if it creates a full share for the broker (omnibus has .6 shares and you sell him .5 they would likely flip that out to the street with the full share portion of your order. This would not have impact to outstanding shares and all cost are operational and with the broker handling the Div reinvestment service.",
"title": ""
},
{
"docid": "414505",
"text": "\"The key difference I've found between a stock split and a stock dividend – of the exact same stock and class, as opposed to a spin-off – seems to be from the company's own accounting perspective. There doesn't appear to be any actual transfer of value to the shareholder with either kind of transaction; i.e. in theory, each transaction would be immaterial to the value of your holdings. With respect to the company's accounting, a stock split affects the par value of the shares, whereas a stock dividend reduces the retained earnings account in order to increase paid-in or contributed capital. I found a good online source which explains the history behind this accounting difference: McGraw-Hill - Intermediate Accounting eBook, 6/e - Chapter 18 - Stock Dividends and Splits. Small quote: [...] Besides being based on fallacious reasoning, accounting for stock dividends by artificially reclassifying “earned” capital as “invested” capital conflicts with the reporting objective of reporting shareholders' equity by source. Despite these limitations, this outdated accounting standard still applies. Since neither the corporation nor its shareholders apparently benefits from stock dividends, why do companies declare them?23 Occasionally, a company tries to give shareholders the illusion that they are receiving a real dividend. Another reason is merely to enable the corporation to take advantage of the accepted accounting practice of capitalizing retained earnings. Specifically, a company might wish to reduce an existing balance in retained earnings—otherwise available for cash dividends—so it can reinvest the earned assets represented by that balance without carrying a large balance in retained earnings. [...] There's a lot more on that page, before and after, worth reading. From another book: Google Books - Comparative Income Taxation, a Structural Analysis - page 314 - Stock Dividends. Small quote: The distribution of dividends in the form of stock or \"\"bonus\"\" shares to existing shareholders typically involves a transfer for corporate law purposes of retained earnings into stated capital. It can been [sic] viewed as a deemed distribution of a cash dividend to the shareholders followed by a corresponding contribution to capital or as solely as an event at the corporate level which has no effect on the shareholders whose economic interest in the corporation is unchanged by the receipt of additional shares. The systems have taken varied approaches to the stock dividend problem. The treatment is in part a function of the rules dealing with distributions of stated capital. [emphases above are mine] [... continues w/descriptions of different countries' tax treatments of the kinds of stock dividends. Includes U.S., Sweden, Japan, Netherlands, Canada, Australia, U.K., France, Germany. ...] As far as why a corporation might want to capitalize earnings and reduce the equity otherwise available for dividends, I can only imagine that, ignoring taxes for a moment, that it may have something to do with capital ratios that need to be maintained for financing or regulatory purposes? Yet, I remain curious. If I discover more on this then I'll update my answer. Additional resources:\"",
"title": ""
},
{
"docid": "308048",
"text": "It is absolutely legal. While studying on a F-1 you would typically be considered a non-resident alien for tax purposes. You can trade stocks, just like any other foreigner having an account with a US- or non-US based brokerage firm. Make sure to account for profit made on dividends/capital gain when doing your US taxes. A software package provided by your university for doing taxes might not be adequate for this.",
"title": ""
},
{
"docid": "211414",
"text": "\"For any accounts where you have a wish to keep track of dividends, gains and losses, etc., you will have to set up a an account to hold the separately listed securities. It looks like you already know how to do this. Here the trading accounts will help you, especially if you have Finance:Quote set up (to pull security prices from the internet). For the actively-managed accounts, you can just create each managed account and NOT fill it with the separate securities. You can record the changes in that account in summary each month/year as you prefer. So, you might set up your chart of accounts to include these assets: And this income: The actively-managed accounts will each get set up as Type \"\"Stock.\"\" You will create one fake security for each account, which will get your unrealized gains/losses on active accounts showing up in your trading accounts. The fake securities will NOT be pulling prices from the internet. Go to Tools -> Securities Editor -> Add and type in a name such as \"\"Merrill Lynch Brokerage,\"\" a symbol such as \"\"ML1,\"\" and in the \"\"Type\"\" field input something like \"\"Actively Managed.\"\" In your self-managed accounts, you will record dividends and sales as they occur, and your securities will be set to get quotes online. You can follow the general GnuCash guides for this. In your too-many-transactions actively traded accounts, maybe once a month you will gather up your statements and enter the activity in summary to tie the changes in cost basis. I would suggest making each fake \"\"share\"\" equal $1, so if you have a $505 dividend, you buy 505 \"\"shares\"\" with it. So, you might have these transactions for your brokerage account with Merrill Lynch (for example): When you have finished making your period-end summary entries for all the actively-managed accounts, double-check that the share balances of your actively-managed accounts match the cost basis amounts on your statements. Remember that each fake \"\"share\"\" is worth $1 when you enter it. Once the cost basis is tied, you can go into the price editor (Tools -> Price Editor) and enter a new \"\"price\"\" as of the period-end date for each actively-managed account. The price will be \"\"Value of Active Acct at Period-End/Cost of Active Acct at Period-End.\"\" So, if your account was worth $1908 but had a cost basis of $505 on Jan. 31, you would type \"\"1908/505\"\" in the price field and Jan. 31, 2017 in the date field. When you run your reports, you will want to choose the price source as \"\"Nearest in Time\"\" so that GnuCash grabs the correct quotes. This should make your actively-managed accounts have the correct activity in summary in your GnuCash income accounts and let them work well with the Trading Accounts feature.\"",
"title": ""
},
{
"docid": "354638",
"text": "\"This is an excellent question, one that I've pondered before as well. Here's how I've reconciled it in my mind. Why should we agree that a stock is worth anything? After all, if I purchase a share of said company, I own some small percentage of all of its assets, like land, capital equipment, accounts receivable, cash and securities holdings, etc., as others have pointed out. Notionally, that seems like it should be \"\"worth\"\" something. However, that doesn't give me the right to lay claim to them at will, as I'm just a (very small) minority shareholder. The old adage says that \"\"something is only worth what someone is willing to pay you for it.\"\" That share of stock doesn't actually give me any liquid control over the company's assets, so why should someone else be willing to pay me something for it? As you noted, one reason why a stock might be attractive to someone else is as a (potentially tax-advantaged) revenue stream via dividends. Especially in this low-interest-rate environment, this might well exceed that which I might obtain in the bond market. The payment of income to the investor is one way that a stock might have some \"\"inherent value\"\" that is attractive to investors. As you asked, though, what if the stock doesn't pay dividends? As a small shareholder, what's in it for me? Without any dividend payments, there's no regular method of receiving my invested capital back, so why should I, or anyone else, be willing to purchase the stock to begin with? I can think of a couple reasons: Expectation of a future dividend. You may believe that at some point in the future, the company will begin to pay a dividend to investors. Dividends are paid as a percentage of a company's total profits, so it may make sense to purchase the stock now, while there is no dividend, banking on growth during the no-dividend period that will result in even higher capital returns later. This kind of skirts your question: a non-dividend-paying stock might be worth something because it might turn into a dividend-paying stock in the future. Expectation of a future acquisition. This addresses the original premise of my argument above. If I can't, as a small shareholder, directly access the assets of the company, why should I attribute any value to that small piece of ownership? Because some other entity might be willing to pay me for it in the future. In the event of an acquisition, I will receive either cash or another company's shares in compensation, which often results in a capital gain for me as a shareholder. If I obtain a capital gain via cash as part of the deal, then this proves my point: the original, non-dividend-paying stock was worth something because some other entity decided to acquire the company, paying me more cash than I paid for my shares. They are willing to pay this price for the company because they can then reap its profits in the future. If I obtain a capital gain via stock in as part of the deal, then the process restarts in some sense. Maybe the new stock pays dividends. Otherwise, perhaps the new company will do something to make its stock worth more in the future, based on the same future expectations. The fact that ownership in a stock can hold such positive future expectations makes them \"\"worth something\"\" at any given time; if you purchase a stock and then want to sell it later, someone else is willing to purchase it from you so they can obtain the right to experience a positive capital return in the future. While stock valuation schemes will vary, both dividends and acquisition prices are related to a company's profits: This provides a connection between a company's profitability, expectations of future growth, and its stock price today, whether it currently pays dividends or not.\"",
"title": ""
},
{
"docid": "287322",
"text": "You must understand that: So, if you -- the prospective buyer -- are in Waukegan, do you take the train all the way to New York City just to buy 100 shares of stock? No. That would be absurdly expensive. So, you hire an agent in NYC who will broker a deal for you in the exchange. Fast forward 100 years, to the time when instant communications is available. Why do we now still need brokerages, when the Exchanges could set up web sites and let you do the trading? The answer is that the Exchanges don't want to have to develop the accounting systems to manage the transactions of hundreds of thousands of small traders, when existing brokerage firms already have those computerized processes in place and are opening their own web sites. Thus, in 2017 we have brokerage firms because of history.",
"title": ""
},
{
"docid": "480967",
"text": "\"Aganju has mentioned put options, which are one good possibility. I would suggest considering an even easier strategy: short selling. Technically you are borrowing the stock from someone and selling it. At some point you repurchase the stock to return to the lender (\"\"covering your short\"\"). If the stock price has fallen, then when you repurchase it, it will be cheaper and you keep the profit. Short selling sounds complicated but it's actually very easy--your broker takes care of all the details. Just go to your brokerage and click \"\"sell\"\" or \"\"sell short.\"\" You can use a market or limit order just like you were selling something you own. When it sells, you are done. The money gets credited to your account. At some point (after the price falls) you should repurchase it so you don't have a negative position any more, but your brokerage isn't going to hassle you for this unless you bought a lot and the stock price starts rising. There will be limits on how much you can short, depending on how much money is in your account. Some stocks (distressed and small stocks) may sometimes be hard to short, meaning your broker will charge you a kind of interest and/or may not be able to complete your transaction. You will need a margin account (a type of brokerage account) to either use options or short sell. They are easy to come by, though. Note that for a given amount of starting money in your account, puts can give you a much more dramatic gain if the stock price falls. But they can (and often do) expire worthless, causing you to lose all money you have spent on them. If you want to maximize how much you make, use puts. Otherwise I'd short sell. About IPOs, it depends on what you mean. If the IPO has just completed and you want to bet that the share price will fall, either puts or short selling will work. Before an IPO you can't short sell and I doubt you would be able to buy an option either. Foreign stocks? Depends on whether there is an ADR for them that trades on the domestic market and on the details of your brokerage account. Let me put it this way, if you can buy it, you can short sell it.\"",
"title": ""
},
{
"docid": "186538",
"text": "\"How often should one use dollar-cost averaging? Trivially, a dollar cost averaging (DCA) strategy must be used at least twice! More seriously, DCA is a discipline that people (typically investors with relatively small amounts of money to invest each month or each quarter) use to avoid succumbing to the temptation to \"\"time the market\"\". As mhoran_psprep points out, it is well-suited to 401k plans and the like (e.g. 403b plans for educational and non-profit institutions, 457 plans for State employees, etc), and indeed is actually the default option in such plans, since a fixed amount of money gets invested each week, or every two weeks, or every month depending on the payroll schedule. Many plans offer just a few mutual funds in which to invest, though far too many people, having little knowledge or understanding of investments, simply opt for the money-market fund or guaranteed annuity fund in their 4xx plans. In any case, all your money goes to work immediately since all mutual funds let you invest in thousandths of a share. Some 401k/403b/457 plans allow investments in stocks through a brokerage, but I think that using DCA to buy individual stocks in a retirement plan is not a good idea at all. The reasons for this are that not only must shares must be bought in whole numbers (integers) but it is generally cheaper to buy stocks in round lots of 100 (or multiples of 100) shares rather than in odd lots of, say, 37 shares. So buying stocks weekly, or biweekly or monthly in a 401k plan means paying more or having the money sit idle until enough is accumulated to buy 100 shares of a stock at which point the brokerage executes the order to buy the stock; and this is really not DCA at all. Worse yet, if you let the money accumulate but you are the one calling the shots \"\"Buy 100 shares of APPL today\"\" instead of letting the brokerage execute the order when there is enough money, you are likely to be timing the market instead of doing DCA. So, are brokerages useless in retirement fund accounts? No, they can be useful but they are not suitable for DCA strategies involving buying stocks. Stick to mutual funds for DCA. Do people use it across the board on all stock investments? As indicated above, using DCA to buy individual stocks is not the best idea, regardless of whether it is done inside a retirement plan or outside. DCA outside a retirement plan works best if you not trust yourself to stick with the strategy (\"\"Ooops, I forgot to mail the check yesterday; oh, well, I will do it next week\"\") but rather, arrange for your mutual fund company to take the money out of your checking account each week/month/quarter etc, and invest it in whatever fund(s) you have chosen. Most companies have such programs under names such as Automatic Investment Program (AIP) etc. Why not have your bank send the money to the mutual fund company instead? Well, that works too, but my bank charges me for sending the money whereas my mutual fund company does AIP for free. But YMMV. Dollar-cost averaging generally means investing a fixed amount of money on a periodic basis. An alternative strategy, if one has decided that owning 1200 shares of FlyByKnight Co is a good investment to have, is to buy round lots of 100 shares of FBKCO each month. The amount of money invested each month varies, but at the end of the year, the average cost of the 1200 shares is the average of the prices on the 12 days on which the investments were made. Of course, by the end of the year, you might not think FBKCO is worth holding any more. This technique worked best in the \"\"good old days\"\" when blue-chip stocks paid what was for all practical purposes a guaranteed dividend each year, and people bought these stocks with the intention of passing them on to their widows and children.\"",
"title": ""
},
{
"docid": "347651",
"text": "You are young, and therefore have a very long time horizon for investing. Absolutely nothing you do should involve paying any attention to your investments more than once a year (if that). First off, you can only deposit money in an IRA (of whatever kind) if you have taxable income. If you don't, you can still invest, just without the tax benefits of a Roth. My suggestion would be to open an account with a discount brokerage (Schwab, Fidelity, eTrade, etc). The advantage of a brokerage IRA is that you can invest in whatever you want within the account. Then, either buy an S&P 500 or total market index fund within the account, or buy an index-based ETF (like a mutual fund, but trades like a stock). The latter might be better, since many mutual funds have minimum limits, which ETFs do not. Set the account up to reinvest the dividends automatically--S&P 500 yields will far outstrip current savings account yields--and sit back and do nothing for the next 40 or 50 years. Well, except for continuing to make annual contributions to the account, which you should continue to invest in pretty much the same thing until you have enough money (and experience and knowledge) to diversify into bond funds/international funds/individual stocks, etc. Disclaimer: I am not a financial planner. I just manage my own money, and this strategy has mostly kept me from stressing too badly over the last few years of market turmoil.",
"title": ""
},
{
"docid": "141458",
"text": "\"Not really, no. The assumption you're making—withdrawals from a corporation are subject to \"\"[ordinary] income tax\"\"—is simplistic. \"\"Income tax\"\" encompasses many taxes, some more benign than others, owing to credits and exemptions based on the kind of income. Moreover, the choices you listed as benefits in the sole-proprietor case—the RRSP, the TFSA, and capital gains treatment for non-registered investments—all remain open to the owner of a small corporation ... the RRSP to the extent that the owner has received salary to create contribution room. A corporation can even, at some expense, establish a defined benefit (DB) pension plan and exceed individual RRSP contribution limits. Yes, there is a more tax-efficient way for small business owners to benefit when it comes time to retirement. Here is an outline of two things I'm aware of: If your retirement withdrawals from your Canadian small business corporation would constitute withdrawal from the corporation's retained earnings (profits), i.e. income to the corporation that had already been subject to corporate income tax in prior years, then the corporation is able to declare such distributions as dividends and issue you a T5 slip (Statement of Investment Income) instead of a T4 slip (Statement of Remuneration Paid). Dividends received by Canadian residents from Canadian corporations benefit from the Dividend Tax Credit (DTC), which substantially increases the amount of income you can receive without incurring income tax. See TaxTips.ca - Non-eligible (small business) dividend tax credit (DTC). Quote: For a single individual with no income other than taxable Canadian dividends which are eligible for the small business dividend tax credit, in 2014 approximately $35,551 [...] could be earned before any federal* taxes were payable. * Provincial DTCs vary, and so combined federal/provincial maximums vary. See here. If you're wondering about \"\"non-eligible\"\" vs. \"\"eligible\"\": private small business corporation dividends are generally considered non-eligible for the best DTC benefit—but they get some benefit—while a large public corporation's dividends would generally be considered eligible. Eligible/non-eligible has to do with the corporation's own income tax rates; since Canadian small businesses already get a big tax break that large companies don't enjoy, the DTC for small businesses isn't as good as the DTC for public company dividends. Finally, even if there is hardly any same-year income tax advantage in taking dividends over salary from an active small business corporation (when you factor in both the income tax paid by the corporation and the individual), dividends still allow a business owner to smooth his income over time, which can result in a lower lifetime average tax rate. So you can use your business as a retained earnings piggy bank to spin off dividends that attract less tax than ordinary income. But! ... if you can convince somebody to buy your business from you, then you can benefit from the lifetime capital gains exemption of up to $800,000 on qualifying small business shares. i.e. you can receive up to $800K tax-free on the sale of your small business shares. This lifetime capital gains exemption is a big carrot—designed, I believe, to incentivize Canadian entrepreneurs to develop going-concern businesses that have value beyond their own time in the business. This means building things that would make your business worth buying, e.g. a valued brand or product, a customer base, intellectual property, etc. Of course, there are details and conditions with all of what I described, and I am not an accountant, so please consult a qualified, conflict-free professional if you need advice specific to your situation.\"",
"title": ""
}
] |
PLAIN-3155
|
Avoiding Epilepsy Through Diet
|
[
{
"docid": "MED-1981",
"text": "The causes of antibiotic resistance are complex and include human behaviour at many levels of society; the consequences affect everybody in the world. Similarities with climate change are evident. Many efforts have been made to describe the many different facets of antibiotic resistance and the interventions needed to meet the challenge. However, coordinated action is largely absent, especially at the political level, both nationally and internationally. Antibiotics paved the way for unprecedented medical and societal developments, and are today indispensible in all health systems. Achievements in modern medicine, such as major surgery, organ transplantation, treatment of preterm babies, and cancer chemotherapy, which we today take for granted, would not be possible without access to effective treatment for bacterial infections. Within just a few years, we might be faced with dire setbacks, medically, socially, and economically, unless real and unprecedented global coordinated actions are immediately taken. Here, we describe the global situation of antibiotic resistance, its major causes and consequences, and identify key areas in which action is urgently needed. Copyright © 2013 Elsevier Ltd. All rights reserved.",
"title": "Antibiotic resistance-the need for global solutions."
},
{
"docid": "MED-1980",
"text": "Enterobacterial strains producing clavulanic-acid-inhibited extended-spectrum β-lactamases (ESBLs) are increasingly reported worldwide. Conventional detection of ESBL production remains time-consuming (24 to 48 h). Therefore, the ESBL NDP (Nordmann/Dortet/Poirel) test was developed for a rapid identification of ESBLs in Enterobacteriaceae. This biochemical test was based on the in vitro detection of a cephalosporin (cefotaxime) hydrolysis that is inhibited by tazobactam addition. The ESBL activity was evidenced by a color change (red to yellow) of a pH indicator (red phenol) due to carboxyl-acid formation resulting from cefotaxime hydrolysis that was reversed by addition of tazobactam (positive test). The ESBL NDP test was applied to cultured strains (215 ESBL producers and 40 ESBL nonproducers). Its sensitivity and specificity were 92.6% and 100%, respectively. Its sensitivity (100%) was excellent for detection of CTX-M producers. A few ESBL producers (n = 16) that remained susceptible to cefotaxime were not detected. The test was also evaluated on spiked blood cultures and showed excellent sensitivity and specificity (100% for both). The test was rapid (less than 1 h) and cost-effective. It can be implemented in any health care facility and is well adapted for infection control purposes in particular.",
"title": "Rapid Detection of Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae"
},
{
"docid": "MED-2748",
"text": "The consumption of fresh produce is frequently associated with outbreaks of human norovirus (hNoV) disease. To prevent the contamination of fresh produce with hNoV, knowledge of the possible introduction sources of the viruses, such as water, is needed to be able to implement appropriate and efficient preventive measures. Contaminated water used to reconstitute pesticides could be a relevant source of infectious hNoV, determined by the initial level of virus contamination and the persistence of these viruses in reconstituted pesticides. We studied the persistence of hNoV GI.4, hNoV GII.4 and murine norovirus (MNV-1), the only culturable norovirus, in eight different pesticides after 0 and 2h. Virus concentrations were determined by reverse transcriptase PCR, and infectivity of MNV-1 was determined by endpoint dilutions followed by maximum likelihood estimations. MNV-1 was found to remain infectious in seven of the eight tested pesticides at the highest concentration applied in practice. In the presence of the insecticide Vertimec, MNV-1 infectivity decreased rapidly with a 1.9 log(10)-unit reduction at timepoint T(0). Also, the concentration of NoV GI.4 RNA decreased considerably with a 1.7 log(10)-unit reduction; whereas the detected PCR fragment of hNoV GII.4 remained stable. Assuming a similar persistence of infectious MNV-1 and hNoV we can conclude that water containing hNoV used to dilute pesticides may be an important source of infectious hNoV in fresh produce chains. The application of pesticides may therefore not only be a chemical hazard, but also a microbiological hazard for public health. The inclusion of antiviral substances in reconstituted pesticides may be appropriate to reduce the virological health risk posed by the application of pesticides. Copyright © 2012 Elsevier B.V. All rights reserved.",
"title": "Persistence of human norovirus in reconstituted pesticides--pesticide application as a possible source of viruses in fresh produce chains."
},
{
"docid": "MED-4131",
"text": "In this article we estimate the annual cost of illness and quality-adjusted life year (QALY) loss in the United States caused by 14 of the 31 major foodborne pathogens reported on by Scallan et al. (Emerg. Infect. Dis. 17:7-15, 2011), based on their incidence estimates of foodborne illness in the United States. These 14 pathogens account for 95 % of illnesses and hospitalizations and 98 % of deaths due to identifiable pathogens estimated by Scallan et al. We estimate that these 14 pathogens cause $14.0 billion (ranging from $4.4 billion to $33.0 billion) in cost of illness and a loss of 61,000 QALYs (ranging from 19,000 to 145,000 QALYs) per year. Roughly 90 % of this loss is caused by five pathogens: nontyphoidal Salmonella enterica ($3.3 billion; 17,000 QALYs), Campylobacter spp. ($1.7 billion; 13,300 QALYs), Listeria monocytogenes ($2.6 billion; 9,400 QALYs), Toxoplasma gondii ($3 billion; 11,000 QALYs), and norovirus ($2 billion; 5,000 QALYs). A companion article attributes losses estimated in this study to the consumption of specific categories of foods. To arrive at these estimates, for each pathogen we create disease outcome trees that characterize the symptoms, severities, durations, outcomes, and likelihoods of health states associated with that pathogen. We then estimate the cost of illness (medical costs, productivity loss, and valuation of premature mortality) for each pathogen. We also estimate QALY loss for each health state associated with a given pathogen, using the EuroQol 5D scale. Construction of disease outcome trees, outcome-specific cost of illness, and EuroQol 5D scoring are described in greater detail in a second companion article.",
"title": "Annual cost of illness and quality-adjusted life year losses in the United States due to 14 foodborne pathogens."
},
{
"docid": "MED-2744",
"text": "Homicide disproportionately affects persons aged 10-24 years in the United States and consistently ranks in the top three leading causes of death in this age group, resulting in approximately 4,800 deaths and an estimated $9 billion in lost productivity and medical costs in 2010. To investigate trends in homicide among persons aged 10-24 years for the period 1981-2010, CDC analyzed National Vital Statistics System data on deaths caused by homicide of persons in this age group and examined trends by sex, age, race/ethnicity, and mechanism of injury. This report describes the results of that analysis, which indicated that homicide rates varied substantially during the study period, with a sharp rise from 1985 to 1993 followed by a decline that has slowed since 1999. During the period 2000-2010, rates declined for all groups, although the decline was significantly slower for males compared with females and for blacks compared with Hispanics and persons of other racial/ethnic groups. By mechanism of injury, the decline for firearm homicides from 2000 to 2010 was significantly slower than for nonfirearm homicides. The homicide rate among persons aged 10-24 years in 2010 was 7.5 per 100,000, the lowest in the 30-year study period. Primary prevention strategies remain critical, particularly among groups at increased risk for homicide.",
"title": "Homicide rates among persons aged 10-24 years - United States, 1981-2010."
},
{
"docid": "MED-2745",
"text": "The current study was undertaken to acquire data on contamination of chicken parts with Salmonella at retail and to acquire data on cross-contamination of cooked chicken with Salmonella from raw chicken during meal preparation. Whole raw chickens (n = 31) were obtained from local retail stores and cut into two wings, two breasts without skin or bones, two thighs, and two drumsticks. Data for cross-contamination were obtained by cutting up a sterile, cooked chicken breast with the same board and knife used to cut up the raw chicken. The board, knife, and latex gloves used by the food handler were not rinsed or washed before cutting up the sterile, cooked chicken breast, thus providing a worst-case scenario for cross-contamination. Standard curves for the concentration of Salmonella bacteria in 400 ml of buffered peptone water after 6 h of incubation of chicken parts as a function of the initial log number of Salmonella bacteria inoculated onto chicken parts were developed and used to enumerate Salmonella bacteria. Standard curves were not affected by the type of chicken part but did differ (P < 0.05) among the five isolates of Salmonella examined. Consequently, Salmonella bacteria were enumerated on naturally contaminated chicken parts using a standard curve developed with the serotype of Salmonella that was isolated from the original sample. The prevalence of contamination was 3 % (4 of 132), whereas the incidence of cross-contamination was 1.8 % (1 of 57). The positive chicken parts were a thigh from chicken 4, which contained 3 CFU of Salmonella enterica serotype Kentucky, and both wings, one thigh, and one cooked breast portion from chicken 15, which all contained 1 CFU of serotype 8,20:-:z(6). These results indicated that the poultry industry is providing consumers in the studied area with chicken that has a low prevalence and low number of Salmonella bacteria at retail and that has a low incidence and low level of cross-contamination of cooked chicken with Salmonella from raw chicken during meal preparation under a worst-case scenario.",
"title": "Initial contamination of chicken parts with Salmonella at retail and cross-contamination of cooked chicken with Salmonella from raw chicken during ..."
},
{
"docid": "MED-2736",
"text": "Campylobacter represents the leading cause of gastroenteritis in Europe. Campylobacteriosis is mainly due to C. jejuni and C. coli. Poultry meat is the main source of contamination, and cross-contaminations in the consumer's kitchen appear to be the important route for exposure. The aim of this study was to examine the transfer of Campylobacter from naturally contaminated raw poultry products to a cooked chicken product via the cutting board and to determine the characteristics of the involved isolates. This study showed that transfer occurred in nearly 30% of the assays and that both the C. jejuni and C. coli species were able to transfer. Transfer seems to be linked to specific isolates: some were able to transfer during separate trials while others were not. No correlation was found between transfer and adhesion to inert surfaces, but more than 90% of the isolates presented moderate or high adhesion ability. All tested isolates had the ability to adhere and invade Caco-2 cells, but presented high variability between isolates. Our results highlighted the occurrence of Campylobacter cross-contamination via the cutting board in the kitchen. Moreover, they provided new interesting data to be considered in risk assessment studies. Copyright © 2013 Elsevier B.V. All rights reserved.",
"title": "Characterization of Campylobacter spp. transferred from naturally contaminated chicken legs to cooked chicken slices via a cutting board."
},
{
"docid": "MED-2741",
"text": "Overcrowding stress is a reality in the poultry industry. Chickens exposed to long-term stressful situations present a reduction of welfare and immunosuppression. We designed this experiment to analyse the effects from overcrowding stress of 16 birds/m(2) on performance parameters, serum corticosterone levels, the relative weight of the bursa of Fabricius, plasma IgA and IgG levels, intestinal integrity, macrophage activity and experimental Salmonella Enteritidis invasion. The results of this study indicate that overcrowding stress decreased performance parameters, induced enteritis and decreased macrophage activity and the relative bursa weight in broiler chickens. When the chickens were similarly stressed and infected with Salmonella Enteritidis, there was an increase in feed conversion and a decrease in plasma IgG levels in the stressed and Salmonella-infected birds. We observed moderate enteritis throughout the duodenum of chickens stressed and infected with Salmonella. The overcrowding stress decreased the macrophage phagocytosis intensity and increased Salmonella Enteritidis counts in the livers of birds challenged with the pathogenic bacterium. Overcrowding stress via the hypothalamic-pituitary-adrenal axis that is associated with an increase in corticosterone and enteritis might influence the quality of the intestinal immune barrier and the integrity of the small intestine. This effect allowed pathogenic bacteria to migrate through the intestinal mucosa, resulting in inflammatory infiltration and decreased nutrient absorption. The data strengthen the hypothesis that control of the welfare of chickens and avoidance of stress from overcrowding in poultry production are relevant factors for the maintenance of intestinal integrity, performance and decreased susceptibility to Salmonella infection.",
"title": "Overcrowding stress decreases macrophage activity and increases Salmonella Enteritidis invasion in broiler chickens."
},
{
"docid": "MED-2742",
"text": "A national telephone survey was conducted of 1,620 randomly selected U.S. residents who spoke English, were at least 18 years old, and resided in households with kitchen facilities. Respondents were interviewed about their recognition of foodborne pathogens, foods at risk for transmitting infection, knowledge of safe food handling, and food-handling practices. One-third of the respondents who prepared meals reported unsafe food hygiene practices: e.g., they did not wash hands or take precautions to prevent cross-contamination from raw meat. Unsafe practices were reported more often by men, adults 18 to 29 years of age, and occasional food preparers than by women, persons 30 years old or older, and frequent food preparers. Respondents who identified a food vehicle for Salmonella spp. were more likely to report washing their hands and cleaning cutting boards after preparing raw meat and poultry. The results raise concerns about consumer food-handling practices. The influence of food safety training, food-handling experience, and age on food-handling practices should be studied further. Awareness of a food vehicle for Salmonella spp., for example, may indicate knowledge of the etiology of foodborne disease that promotes safe food handling. Understanding the factors associated with safe food handling will assist in development of effective safe-food instruction programs.",
"title": "Consumer knowledge of foodborne microbial hazards and food-handling practices."
},
{
"docid": "MED-4672",
"text": "Neurocysticercosis cases were identified in 1991 in an Orthodox Jewish community. Transmission was linked to tapeworm-infected immigrant housekeepers from countries where Taenia solium is endemic. To evaluate the extent of and risks for locally acquired cysticercosis, a seroprevalence survey was conducted in 9% of the households in this community. Cysticercosis antibodies were detected in 23 (1.3%) of 1,789 persons from 612 families. All 23 seropositive persons were asymptomatic, and no intracerebral lesions were found for the 21 seropositive persons who underwent brain imaging. Seropositivity was associated with female sex (relative risk [RR] = 2.45, P = 0.049), hiring a domestic worker for child care duties (RR = 3.79, P = 0.05), and with employees from Central America (RR = 2.70, P = 0.0001). Exposure to T. solium in this community is unexpectedly high. Widespread employment of domestic workers from endemic regions and high employee turnover contributes to exposure risk.",
"title": "Seroprevalence of cysticercosis in an Orthodox Jewish community."
},
{
"docid": "MED-2673",
"text": "Transglutaminase is an enzyme that can be used to cross-link pieces of meat, fish or meat products. The resulting product gives the optical impression of an intact chunk of meat. The usage of transglutaminase as a food additive is permitted in some countries. However, its utilisation has to be declared to ensure transparency for consumers. This paper describes two orthogonal analytical methods suited for the detection of technological relevant transglutaminase concentrations (around 25 mg pure enzyme in 1 kg of product) in meat and meat products. The mass spectrometry-based approach relies on a previous digestion with Achromobacter lyticus protease and LC-MS/MS separation and detection. Sufficient selectivity was obtained by monitoring four different peptides. The orthogonal (complementary and independent), ELISA-based approach relies on two commercially available bacterial transglutaminase-specific antibodies, combined to a sandwich ELISA. The two methods were tested by analysing some 60 samples obtained from the market.",
"title": "Determination of microbial transglutaminase in meat and meat products."
},
{
"docid": "MED-2749",
"text": "Noroviruses are the leading cause of foodborne illness in the United States. To better guide interventions, we analyzed 2,922 foodborne disease outbreaks for which norovirus was the suspected or confirmed cause, which had been reported to the Foodborne Disease Outbreak Surveillance System of the Centers for Disease Control and Prevention during 2001–2008. On average, 365 foodborne norovirus outbreaks were reported annually, resulting in an estimated 10,324 illnesses, 1,247 health care provider visits, 156 hospitalizations, and 1 death. In 364 outbreaks attributed to a single commodity, leafy vegetables (33%), fruits/nuts (16%), and mollusks (13%) were implicated most commonly. Infected food handlers were the source of 53% of outbreaks and may have contributed to 82% of outbreaks. Most foods were likely contaminated during preparation and service, except for mollusks, and occasionally, produce was contaminated during production and processing. Interventions to reduce the frequency of foodborne norovirus outbreaks should focus on food workers and production of produce and shellfish.",
"title": "Epidemiology of Foodborne Norovirus Outbreaks, United States, 2001–2008"
},
{
"docid": "MED-4136",
"text": "BACKGROUND: In the United States, contaminated food causes approximately 1,000 reported disease outbreaks and an estimated 48 million illnesses, 128,000 METHODS: The Foodborne Diseases Active Surveillance Network (FoodNet) conducts surveillance among 15% of the U.S. population for laboratory-confirmed infections with nine pathogens transmitted commonly through food. Overall and pathogen-specific changes in incidence were estimated from 1996-1998 to 2010 and from 2006-2008 to 2010.hospitalizations, and 3,000 deaths annually. This report summarizes 2010 surveillance data and describes trends since 1996. RESULTS: A total of 19,089 infections, 4,247 hospitalizations, and 68 deaths were reported from FoodNet sites in 2010. Salmonella infection was the most common infection reported (17.6 illnesses per 100,000 persons) and was associated with the largest number of hospitalizations (2,290) and deaths (29); no significant change in incidence of Salmonella infection has occurred since the start of surveillance during 1996-1998. Shiga toxin-producing Escherichia coli (STEC) O157 infection caused 0.9 illnesses per 100,000. Compared with 1996-1998, overall incidence of infection with six key pathogens in 2010 was 23% lower, and pathogen-specific incidence was lower for Campylobacter, Listeria, STEC O157, Shigella, and Yersinia infection but higher for Vibrio infection. Compared with a more recent period, 2006--2008, incidence in 2010 was lower for STEC O157 and Shigella infection but higher for Vibrio infection. CONCLUSIONS: The incidence of STEC O157 infection has declined to reach the 2010 national health objective target of ≥1 case per 100,000. This success, as well as marked declines since 1996-1998 in overall incidence of six key foodborne infections, demonstrates the feasibility of preventing foodborne illnesses. IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Salmonella infection should be targeted because it has not declined significantly in more than a decade, and other data indicate that it is one of the most common foodborne infections, resulting in an estimated $365 million in direct medical costs annually. The prevention measures that reduced STEC O157 infection need to be applied more broadly to reduce Salmonella and other infections. Effective measures from farm to table include preventing contamination of meat during slaughter and of all foods, including produce, during processing and preparation; cooking meat thoroughly; vigorously detecting and investigating outbreaks; and recalling contaminated food.",
"title": "Vital signs: incidence and trends of infection with pathogens transmitted commonly through food--foodborne diseases active surveillance network, 10..."
},
{
"docid": "MED-3884",
"text": "Microbes have evolved over 3.5 billion years and are arguably the most adaptable organisms on earth. Restricted genetically by their inability to reproduce sexually, bacteria have acquired several additional mechanisms by which to exchange genetic material horizontally. Such mechanisms have allowed bacteria to inhabit some of the most inhospitable environments on earth. It is thus hardly surprising that when faced with a barrage of inimical chemicals (antibiotics) they have responded with an equal and opposite force. This article compares and contrasts the evolution of antimicrobial resistance to beta-lactam antibiotics over the last 70 years in two bacterial species, namely Staphylococcus aureus, a highly evolved human pathogen, and Pseudomonas aeruginosa, an opportunistic nosocomial pathogen.",
"title": "The 2009 Garrod lecture: the evolution of antimicrobial resistance: a Darwinian perspective."
},
{
"docid": "MED-2746",
"text": "Foods prepared in the kitchen can become cross-contaminated with Campylobacter by contacting raw products, particularly skinned poultry. We measured the percent transfer rate from naturally contaminated poultry legs purchased in supermarkets. Transfer of Campylobacter from skin (n = 43) and from meat (n = 12) to high-density polyethylene cutting board surfaces was quantitatively assessed after contact times of 1 and 10 min. The percent transfer rate was defined as the ratio between the number of Campylobacter cells counted on the cutting board surface and the initial numbers of Campylobacter naturally present on the skin (i.e., the sum of Campylobacter cells on the skin and board). Qualitative transfer occurred in 60.5% (95% confidence interval, 45.5 to 75.4) of the naturally contaminated legs studied and reached 80.6% (95% confidence interval, 63.0 to 98.2) in the subpopulation of legs that were in contact with the surface for 10 min. The percent transfer rate varied from 5 x 10(-2)% to 35.7% and was observed as being significantly different (Kruskall-Wallis test, P < 0.025) and inversely related to the initial counts on poultry skin. This study provides quantitative data describing the evolution of the proportion of Campylobacter organisms transferred from naturally contaminated poultry under kitchen conditions. We emphasize the linear relationship between the initial load of Campylobacter on the skin and the value of the percent transfer rate. This work confirms the need for modeling transfer as a function of initial load of Campylobacter on leg skin, the weight of poultry pieces, and the duration of contact between the skin and surface.",
"title": "Campylobacter transfer from naturally contaminated chicken thighs to cutting boards is inversely related to initial load."
},
{
"docid": "MED-2743",
"text": "In June 2012, the Oregon Health Authority and the Washington State Department of Health noted an increase in the number of Salmonella enterica serotype Heidelberg clinical isolates sharing an identical pulsed-field gel electrophoresis (PFGE) pattern. In 2004, this pattern had been linked to chicken from Foster Farms by the Washington State Department of Health; preliminary 2012 interviews with infected persons also indicated exposure to Foster Farms chicken. On August 2, 2012, CDC's PulseNet* detected a cluster of 19 Salmonella Heidelberg clinical isolates matching the outbreak pattern. This report summarizes the investigation by CDC, state and local health departments, the U.S. Department of Agriculture's Food Safety and Inspection Service (USDA-FSIS), and the Food and Drug Administration (FDA) and reinforces the importance of safe food handling to prevent illness. A total of 134 cases from 13 states were identified, including 33 patients who were hospitalized. This multifaceted investigation used standard epidemiologic and laboratory data along with patient shopper card purchase information, and PFGE data from the retail meat component of the National Antimicrobial Resistance Monitoring System (NARMS)†, a relatively novel tool in outbreak investigation, to link the outbreak strain to chicken from Foster Farms.",
"title": "Outbreak of Salmonella Heidelberg infections linked to a single poultry producer -- 13 states, 2012-2013."
},
{
"docid": "MED-3889",
"text": "Contamination of retail chicken meat by Extended Spectrum Beta-Lactamase (ESBL) producing bacteria likely contributes to the increasing incidence of infections with these bacteria in humans. This study aimed to compare the prevalence and load of ESBL positive isolates between organic and conventional retail chicken meat samples, and to compare the distribution of ESBL genes, strain genotypes and co-resistance. In 2010, 98 raw chicken breasts (n=60 conventional; n=38 organic) were collected from 12 local stores in the Netherlands. Prevalence of ESBL producing micro-organisms was 100% on conventional and 84% on organic samples (p<0.001). Median loads of ESBL producing micro-organisms were 80 (range <20-1360) in conventional, and <20 (range 0-260) CFU/25 g in organic samples (p=0.001). The distribution of ESBL genes in conventional samples and organic samples was 42% versus 56%, respectively (N.S.), for CTX-M-1, 20% versus 42% (N.S.) for TEM-52, and 23% versus 3% (p<0.001) for SHV-12. CTX-M-2 (7%), SHV-2 (5%) and TEM-20 (3%) were exclusively found in conventional samples. Co-resistance rates of ESBL positive isolates were not different between conventional and organic samples (co-trimoxazole 56%, ciprofloxacin 14%, and tobramycin 2%), except for tetracycline, 73% and 46%, respectively, p<0.001). Six of 14 conventional meat samples harbored 4 MLST types also reported in humans and 5 of 10 organic samples harbored 3 MLST types also reported in humans (2 ST10, 2 ST23, ST354). In conclusion, the majority of organic chicken meat samples were also contaminated with ESBL producing E. coli, and the ESBL genes and strain types were largely the same as in conventional meat samples. Copyright © 2011 Elsevier B.V. All rights reserved.",
"title": "Comparison of ESBL contamination in organic and conventional retail chicken meat."
},
{
"docid": "MED-1983",
"text": "Methicillin-resistant Staphylococcus aureus (MRSA) is a pathogen that has developed resistance to beta-lactam antibiotics and has been isolated at low population numbers in retail meat products. The objectives of this study were to estimate the potential transfer of MRSA from contaminated retail pork products to food contact surfaces and to estimate the potential for human exposure to MRSA by contact with those contaminated surfaces. Pork loins, bacon, and fresh pork sausage were inoculated with a four-strain mixed MRSA culture over a range of populations from approximately 4 to 8 log, vacuum packaged, and stored for 2 weeks at 5°C to simulate normal packaging and distribution. Primary transfer was determined by placing inoculated products on knife blades, cutting boards, and a human skin model (pork skin) for 5 min. Secondary transfer was determined by placing an inoculated product on the contact surface, removing it, and then placing the secondary contact surface on the initial contact surface. A pork skin model was used to simulate transfer to human skin by placing it into contact with the contact surface. The percentages of transfer for primary transfer from the inoculated products to the cutting board ranged from 39 to 49%, while the percentages of transfer to the knife ranged from 17 to 42%. The percentages of transfer from the inoculated products to the pork skin ranged from 26 to 36%. The secondary transfer percentages ranged from 2.2 to 5.2% across all products and contact surfaces. Statistical analysis showed no significant differences in the amounts of transfer between transfer surfaces and across cell concentrations.",
"title": "Transfer of methicillin-resistant Staphylococcus aureus from retail pork products onto food contact surfaces and the potential for consumer exposure."
},
{
"docid": "MED-1979",
"text": "Methicillin-resistant Staphylococcus aureus (MRSA) is a major global public health concern and could be a food safety issue. Recurrent reports have documented that pig herds are an important reservoir for MRSA, specifically the livestock-associated sequence type 398. The high prevalence of MRSA in pig primary production facilities and the frequent detection of MRSA of the same types in pork and pig meat products raise the question of underlying mechanisms behind the introduction and transmission of MRSA along the pork production chain. A comprehensive review of current literature on the worldwide presence of livestock-associated MRSA in various steps of the pork production chain revealed that the slaughter process plays a decisive role in MRSA transmission from farm to fork. Superficial heat treatments such as scalding and flaming during the slaughter process can significantly reduce the burden of MRSA on the carcasses. However, recontamination with MRSA might occur via surface treating machinery, as a result of fecal contamination at evisceration, or via increased human handling during meat processing. By optimizing processes for carcass decontamination and avoiding recontamination by effective cleaning and personal hygiene management, transmission of MRSA from pig to pork can be minimized.",
"title": "From pig to pork: methicillin-resistant Staphylococcus aureus in the pork production chain."
},
{
"docid": "MED-5169",
"text": "Fourteen sites evenly divided between the household kitchen and bathroom were monitored on a weekly basis for numbers of faecal coliforms, total coliforms and heterotrophic plate count bacteria. The first 10 weeks comprised the control period, hypochlorite cleaning products were introduced into the household during the second 10 weeks, and a strict cleaning regimen using hypochlorite products was implemented during the last 10 weeks. The kitchen was more heavily contaminated than the bathroom, with the toilet seat being the least contaminated site. The highest concentrations of all three classes of bacteria were found on sites that were moist environments and/or were frequently touched; these included the sponge/dishcloth, the kitchen sink drain area, the bath sink drain area, and the kitchen faucet handle(s). The implementation of a cleaning regimen with common household hypochlorite products resulted in the significant reduction of all three classes of bacteria at these four sites and other household sites.",
"title": "Reduction of faecal coliform, coliform and heterotrophic plate count bacteria in the household kitchen and bathroom by disinfection with hypochlori..."
},
{
"docid": "MED-1982",
"text": "In a study of 40 methicillin-resistant Staphylococcus aureus (MRSA) carriers, hand contamination was equally likely after contact with commonly examined skin sites and commonly touched environmental surfaces in patient rooms (40% vs 45%). These findings suggest that contaminated surfaces may be an important source of MRSA transmission.",
"title": "Contamination of hands with methicillin-resistant Staphylococcus aureus after contact with environmental surfaces and after contact with the skin o..."
},
{
"docid": "MED-1978",
"text": "Context Nearly 80% of antibiotics in the United States are sold for use in livestock feeds. The manure produced by these livestock contains antibiotic-resistant bacteria, resistance genes, and antibiotics, and is subsequently applied to crop fields where it may put community members at risk for antibiotic-resistant infections. Objective To assess the association between individual exposure to swine and dairy/veal industrial agriculture and risk of methicillin-resistant Staphylococcus aureus (MRSA) infection. Design, Setting, and Participants A population-based, nested case-control study of Geisinger primary care patients in Pennsylvania from 2005–2010. Incident MRSA cases were identified using electronic health records, classified as community-associated or healthcare-associated, and frequency-matched to randomly selected controls and patients with skin and soft tissue infection. Nutrient management plans were used to create two exposure variables: seasonal crop field manure application and number of livestock at the operation. In a sub-study we collected 200 isolates from patients stratified by location of diagnosis and proximity to livestock operations. Main outcome measures Community-associated MRSA, healthcare associated-MRSA, and skin and soft tissue infection status (with no history of MRSA) compared to controls. Results From 446,480 patients, 1539 community-associated MRSA, 1335 healthcare-associated MRSA, 2895 skin and soft tissue infection cases, and 2914 controls were included. After adjustment for MRSA risk factors, the highest quartile of swine crop field exposure was significantly associated with community-associated MRSA, healthcare-associated MRSA, and skin and soft tissue infection case status (adjusted odds ratio, 1.38 [95% CI, 1.13–1.69], 1.30 [95% CI, 1.05–1.61], and 1.37 [95% CI, 1.18–1.60], respectively); and there was a trend of increasing odds across quartiles for each outcome (all P for trend ≤0.01). There were similar but weaker associations of swine operations with community-associated MRSA and skin and soft tissue infection. Molecular testing of 200 isolates identified 31 unique spa types, none of which corresponded to CC398, but some have been previously found in swine. Conclusion Proximity to swine manure application to crop fields and livestock operations each was associated with MRSA and skin and soft tissue infection. These findings contribute to the growing concern about the potential public health impacts of high-density livestock production.",
"title": "High-density livestock operations, crop field application of manure, and risk of community-associated methicillin-resistant Staphylococcus aureus infection, Pennsylvania, USA"
},
{
"docid": "MED-1977",
"text": "Reports have documented colonization of swine in Europe, North America and more recently in China with livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA). Contamination of pig farmers, veterinarians and abattoir workers with these strains has been observed. However, although contamination levels of 10% of retail pork were reported from the Netherlands and Canada, there are limited data of contamination rates of workers handling raw meat. We investigated the rates of MRSA contamination of local butchers working in wet markets, where recently slaughtered pigs are cut up. Nasal swabs collected from 300 pork butchers at markets throughout Hong Kong were enriched in brain heart infusion broth with 5% salt and cultured on MRSASelect(®) . Isolates were confirmed as Staphylococcus aureus and susceptibility testing performed. The presence of mecA was confirmed, SCCmec and spa type determined and relatedness investigated by PFGE. Subjects completed a questionnaire on MRSA carriage risk factors. Seventeen samples (5.6%) yielded MRSA, 15 harbouring SCCmec IVb. Ten strains were t899 (CC9), previously reported from local pig carcasses. Five strains were healthcare associated: SCCmec type II, t701(CC6), colonizing two subjects at the same establishment, and single isolates of t008 (CC8), t002 (CC5) and t123 (CC45). The remaining isolates were t359 (CC97), previously reported from buffaloes, and t375 (CC5), reported from bovine milk. None of these butchers reported recent hospitalization or a healthcare worker in the family. Two had recently received antibiotics, one for a skin infection. Four reported wound infections within the last year. All were exposed to meat for >9 h per day. Carriage of MRSA was higher in butchers than in the general community. Although five strains were probably of healthcare origin, the high incidence of t899 (CC9) suggests that cross-contamination from pork occurs frequently. Washing of hands after touching raw pork is advised. © 2012 Blackwell Verlag GmbH.",
"title": "Colonization of butchers with livestock-associated methicillin-resistant Staphylococcus aureus."
},
{
"docid": "MED-2747",
"text": "Each year, >9 million foodborne illnesses are estimated to be caused by major pathogens acquired in the United States. Preventing these illnesses is challenging because resources are limited and linking individual illnesses to a particular food is rarely possible except during an outbreak. We developed a method of attributing illnesses to food commodities that uses data from outbreaks associated with both simple and complex foods. Using data from outbreak-associated illnesses for 1998–2008, we estimated annual US foodborne illnesses, hospitalizations, and deaths attributable to each of 17 food commodities. We attributed 46% of illnesses to produce and found that more deaths were attributed to poultry than to any other commodity. To the extent that these estimates reflect the commodities causing all foodborne illness, they indicate that efforts are particularly needed to prevent contamination of produce and poultry. Methods to incorporate data from other sources are needed to improve attribution estimates for some commodities and agents.",
"title": "Attribution of Foodborne Illnesses, Hospitalizations, and Deaths to Food Commodities by using Outbreak Data, United States, 1998–2008"
},
{
"docid": "MED-3880",
"text": "A common approach to reducing microbial contamination has been the implementation of a Hazard Analysis and Critical Control Point (HACCP) program to prevent or reduce contamination during production. One example is the Pathogen Reduction HACCP program implemented by the U.S. Department of Agriculture's Food Safety and Inspection Service (FSIS). This program consisted of a staged implementation between 1996 and 2000 to reduce microbial contamination on meat and poultry products. Of the commodities regulated by FSIS, one of the largest observed reductions was for Salmonella contamination on broiler chicken carcasses. Nevertheless, how this reduction might have influenced the total number of salmonellosis cases in the United States has not been assessed. This study incorporates information from public health surveillance and surveys of the poultry slaughter industry into a model that estimates the number of broiler-related salmonellosis cases through time. The model estimates that-following the 56% reduction in the proportion of contaminated broiler carcasses observed between 1995 and 2000-approximately 190,000 fewer annual salmonellosis cases (attributed to broilers) occurred in 2000 compared with 1995. The uncertainty bounds for this estimate range from approximately 37,000 to 500,000 illnesses. Estimated illnesses prevented, due to the more modest reduction in contamination of 13% between 2000 and 2007, were not statistically significant. An analysis relating the necessary magnitude of change in contamination required for detection via human surveillance also is provided.",
"title": "Estimating changes in public health following implementation of hazard analysis and critical control point in the United States broiler slaughter i..."
},
{
"docid": "MED-2740",
"text": "To determine the burden of Salmonella infections in the United States, Foodborne Diseases Active Surveillance Network (FoodNet) investigators conducted population-based active surveillance for culture-confirmed Salmonella infections during 1996-1999 at FoodNet laboratories. In addition, all clinical microbiology FoodNet laboratories were surveyed to determine their practices for isolating Salmonella. Telephone interviews were also conducted among residents of the FoodNet sites to determine the proportion of persons with diarrheal illness who sought medical care and the proportion who submitted stool specimens for bacterial culture. Using our model, we estimated that there were 1.4 million nontyphoidal Salmonella infections in the United States, resulting in 168,000 physician office visits per year during 1996-1999. Including both culture-confirmed infections and those not confirmed by culture, we estimated that Salmonella infections resulted in 15,000 hospitalizations and 400 deaths annually. These estimates indicate that salmonellosis presents a major ongoing burden to public health.",
"title": "FoodNet estimate of the burden of illness caused by nontyphoidal Salmonella infections in the United States."
},
{
"docid": "MED-2672",
"text": "To quantify objectionable levels of connective tissues, restructured beef products were made with 2·5 and 5% added tendon; 5 and 10% added epimysium, gristle, or peri/endomysium; and a control. Initial tenderness (IT), residual connective tissue (CT), and overall texture (OT) were evaluated by a sensory panel. Panelists adversely scored IT, CT, and OT for 2·5 and 5% tendon and CT and OT for 10% epimysium and gristle. CT and OT scores correlated with hydroxyproline content and Lee-Kramer peak shear force for uncooked steaks with added tendon, gristle and epimysium but not peri/endomysium. Acceptable products can be made when raw materials are free of tendons and contain only limited amounts of epimysium. Copyright © 1990. Published by Elsevier Ltd.",
"title": "Effects of added connective tissues on the sensory and mechanical properties of restructured beef steaks."
},
{
"docid": "MED-3886",
"text": "The treatment of bacterial infections is increasingly complicated by the ability of bacteria to develop resistance to antimicrobial agents. Antimicrobial agents are often categorized according to their principal mechanism of action. Mechanisms include interference with cell wall synthesis (e.g., beta-lactams and glycopeptide agents), inhibition of protein synthesis (macrolides and tetracyclines), interference with nucleic acid synthesis (fluoroquinolones and rifampin), inhibition of a metabolic pathway (trimethoprim-sulfamethoxazole), and disruption of bacterial membrane structure (polymyxins and daptomycin). Bacteria may be intrinsically resistant to > or =1 class of antimicrobial agents, or may acquire resistance by de novo mutation or via the acquisition of resistance genes from other organisms. Acquired resistance genes may enable a bacterium to produce enzymes that destroy the antibacterial drug, to express efflux systems that prevent the drug from reaching its intracellular target, to modify the drug's target site, or to produce an alternative metabolic pathway that bypasses the action of the drug. Acquisition of new genetic material by antimicrobial-susceptible bacteria from resistant strains of bacteria may occur through conjugation, transformation, or transduction, with transposons often facilitating the incorporation of the multiple resistance genes into the host's genome or plasmids. Use of antibacterial agents creates selective pressure for the emergence of resistant strains. Herein 3 case histories-one involving Escherichia coli resistance to third-generation cephalosporins, another focusing on the emergence of vancomycin-resistant Staphylococcus aureus, and a third detailing multidrug resistance in Pseudomonas aeruginosa--are reviewed to illustrate the varied ways in which resistant bacteria develop.",
"title": "Mechanisms of antimicrobial resistance in bacteria."
},
{
"docid": "MED-3887",
"text": "Summary: Antimicrobials are valuable therapeutics whose efficacy is seriously compromised by the emergence and spread of antimicrobial resistance. The provision of antibiotics to food animals encompasses a wide variety of nontherapeutic purposes that include growth promotion. The concern over resistance emergence and spread to people by nontherapeutic use of antimicrobials has led to conflicted practices and opinions. Considerable evidence supported the removal of nontherapeutic antimicrobials (NTAs) in Europe, based on the “precautionary principle.” Still, concrete scientific evidence of the favorable versus unfavorable consequences of NTAs is not clear to all stakeholders. Substantial data show elevated antibiotic resistance in bacteria associated with animals fed NTAs and their food products. This resistance spreads to other animals and humans—directly by contact and indirectly via the food chain, water, air, and manured and sludge-fertilized soils. Modern genetic techniques are making advances in deciphering the ecological impact of NTAs, but modeling efforts are thwarted by deficits in key knowledge of microbial and antibiotic loads at each stage of the transmission chain. Still, the substantial and expanding volume of evidence reporting animal-to-human spread of resistant bacteria, including that arising from use of NTAs, supports eliminating NTA use in order to reduce the growing environmental load of resistance genes.",
"title": "Food Animals and Antimicrobials: Impacts on Human Health"
},
{
"docid": "MED-3888",
"text": "BACKGROUND: Salmonella enterica causes an estimated 1 million cases of domestically acquired foodborne illness in humans annually in the United States; Enteritidis (SE) is the most common serotype. Public health authorities, regulatory agencies, food producers, and food processors need accurate information about rates and changes in SE infection to implement and evaluate evidence-based control policies and practices. METHODS: We analyzed the incidence of human SE infection during 1996-2009 in the Foodborne Diseases Active Surveillance Network (FoodNet), an active, population-based surveillance system for laboratory-confirmed infections. We compared FoodNet incidence with passively collected data from complementary surveillance systems and with rates of SE isolation from processed chickens and egg products; shell eggs are not routinely tested. We also compared molecular subtyping patterns of SE isolated from humans and chickens. RESULTS: Since the period 1996-1999, the incidence of human SE infection in FoodNet has increased by 44%. This change is mirrored in passive national surveillance data. The greatest relative increases were in young children, older adults, and FoodNet sites in the southern United States. The proportion of patients with SE infection who reported recent international travel has decreased in recent years, whereas the proportion of chickens from which SE was isolated has increased. Similar molecular subtypes of SE are commonly isolated from humans and chickens. CONCLUSIONS: Most SE infections in the United States are acquired from domestic sources, and the problem is growing. Chicken and eggs are likely major sources of SE. Continued close attention to surveillance data is needed to monitor the impact of recent regulatory control measures.",
"title": "Salmonella enterica serotype Enteritidis: increasing incidence of domestically acquired infections."
},
{
"docid": "MED-2671",
"text": "Microbiology of meats has been a subject of great concern in food science and public health in recent years. Although many articles have been devoted to the microbiology of beef, pork, and poultry meats, much less has been written about microbiology of lamb meat and even less on restructured lamb meat. This article presents data on microbiology and shelf-life of fresh lamb meat; restructured meat products, restructured lamb meat products, bacteriology of restructured meat products, and important foodborne pathogens such as Salmonella, Escherichia coli O157:H7, and Listeria monocytogenes in meats and lamb meats. Also, the potential use of sodium and potassium lactates to control foodborne pathogens in meats and restructured lamb meat is reviewed This article should be of interest to all meat scientists, food scientists, and public health microbiologists who are concerned with the safety of meats in general and lamb meat in particular.",
"title": "Microbiology of fresh and restructured lamb meat: a review."
},
{
"docid": "MED-2738",
"text": "Although survey results measuring the safety of consumers' food handling and risky food consumption practices have been published for over 20 years, evaluation of trends is impossible because the designs of published studies are not comparable. The Food Safety Surveys used comparable methods to interview U.S. adults by telephone in 1988, 1993, 2001, 2006, and 2010 about food handling (i.e., cross-contamination prevention) and risky consumption practices (eating raw or undercooked foods from animals) and perceived risk from foodborne illness. Sample sizes ranged from 1,620 to 4,547. Responses were analyzed descriptively, and four indices measuring meat, chicken, and egg cross-contamination, fish cross-contamination, risky consumption, and risk perceptions were analyzed using generalized linear models. The extent of media coverage of food safety issues was also examined. We found a substantial improvement in food handling and consumption practices and an increase in perceived risk from foodborne illness between 1993 and 1998. All indices were stable or declined between 1998 and 2006. Between 2006 and 2010, the two safe food handling practice indices increased significantly, but risk perceptions did not change, and safe consumption declined. Women had safer food handling and consumption practices than men. The oldest and youngest respondents and those with the highest education had the least safe food handling behaviors. Changes in safety of practices over the survey years are consistent with the change in the number of media stories about food safety in the periods between surveys. This finding suggests that increased media attention to food safety issues may raise awareness of food safety hazards and increase vigilance in food handling by consumers.",
"title": "Trends in U.S. consumers' safe handling and consumption of food and their risk perceptions, 1988 through 2010."
},
{
"docid": "MED-3882",
"text": "Salmonella enterica is one of the most common causes of foodborne illness in the United States. Although salmonellosis is usually self-limiting, severe infections typically require antimicrobial treatment, and ceftriaxone, an extended-spectrum cephalosporin (ESC), is commonly used in both adults and children. Surveillance conducted by the National Antimicrobial Resistance Monitoring System (NARMS) has shown a recent increase in ESC resistance among Salmonella Heidelberg isolated from food animals at slaughter, retail meat, and humans. ESC resistance among Salmonella in the United States is usually mediated by a plasmid-encoded bla(CMY) β-lactamase. In 2009, we identified 47 ESC-resistant bla(CMY)-positive Heidelberg isolates from humans (n=18), food animals at slaughter (n=16), and retail meats (n=13) associated with a spike in the prevalence of this serovar. Almost 90% (26/29) of the animal and meat isolates were isolated from chicken carcasses or retail chicken meat. We screened NARMS isolates for the presence of bla(CMY), determined whether the gene was plasmid-encoded, examined pulsed-field gel electrophoresis patterns to assess the genetic diversities of the isolates, and categorized the bla(CMY) plasmids by plasmid incompatibility groups and plasmid multi-locus sequence typing (pMLST). All 47 bla(CMY) genes were found to be plasmid encoded. Incompatibility/replicon typing demonstrated that 41 were IncI1 plasmids, 40 of which only conferred bla(CMY)-associated resistance. Six were IncA/C plasmids that carried additional resistance genes. pMLST of the IncI1-bla(CMY) plasmids showed that 27 (65.8%) were sequence type (ST) 12, the most common ST among bla(CMY)-IncI1 plasmids from Heidelberg isolated from humans. Ten plasmids had a new ST profile, ST66, a type very similar to ST12. This work showed that the 2009 increase in ESC resistance among Salmonella Heidelberg was caused mainly by the dissemination of bla(CMY) on IncI1 and IncA/C plasmids in a variety of genetic backgrounds, and is likely not the result of clonal expansion.",
"title": "Characterization of extended-spectrum cephalosporin-resistant Salmonella enterica serovar Heidelberg isolated from food animals, retail meat, and h..."
},
{
"docid": "MED-4132",
"text": "Understanding the relative public health impact of major microbiological hazards across the food supply is critical for a risk-based national food safety system. This study was conducted to estimate the U.S. health burden of 14 major pathogens in 12 broad categories of food and to then rank the resulting 168 pathogen-food combinations. These pathogens examined were Campylobacter, Clostridium perfringens, Escherichia coli O157:H7, Listeria monocytogenes, norovirus, Salmonella enterica, Toxoplasma gondii, and all other FoodNet pathogens. The health burden associated with each pathogen was measured using new estimates of the cost of illness and loss of quality-adjusted life years (QALYs) from acute and chronic illness and mortality. A new method for attributing illness to foods was developed that relies on both outbreak data and expert elicitation. This method assumes that empirical data are generally preferable to expert judgment; thus, outbreak data were used for attribution except where evidence suggests that these data are considered not representative of food attribution. Based on evaluation of outbreak data, expert elicitation, and published scientific literature, outbreak-based attribution estimates for Campylobacter, Toxoplasma, Cryptosporidium, and Yersinia were determined not representative; therefore, expert-based attribution were included for these four pathogens. Sensitivity analyses were conducted to assess the effect of attribution data assumptions on rankings. Disease burden was concentrated among a relatively small number of pathogen-food combinations. The top 10 pairs were responsible for losses of over $8 billion and 36,000 QALYs, or more than 50 % of the total across all pairs. Across all 14 pathogens, poultry, pork, produce, and complex foods were responsible for nearly 60 % of the total cost of illness and loss of QALYs.",
"title": "Ranking the disease burden of 14 pathogens in food sources in the United States using attribution data from outbreak investigations and expert elic..."
},
{
"docid": "MED-3891",
"text": "Escherichia coli isolates were recovered from the National Antimicrobial Resistance Monitoring System retail meat program and examined for antimicrobial susceptibility. Retail meat samples (n = 11,921) from four U.S. states collected during 2002 to 2008, consisting of 2,988 chicken breast, 2,942 ground turkey, 2,991 ground beef, and 3,000 pork chop samples, were analyzed. A total of 8,286 E. coli isolates were recovered. The greatest numbers of samples contaminated with the organism were chicken (83.5%) and turkey (82.0%), followed by beef (68.9%) and pork (44.0%). Resistance was most common to tetracycline (50.3%), followed by streptomycin (34.6%), sulfamethoxazole-sulfisoxazole (31.6%), ampicillin (22.5%), gentamicin (18.6%), kanamycin (8.4%), amoxicillin-clavulanic acid (6.4%), and cefoxitin (5.2%). Less than 5% of the isolates had resistance to trimethoprim, ceftriaxone, ceftiofur, nalidixic acid, chloramphenicol, and ciprofloxacin. All isolates were susceptible to amikacin. Compared to beef and pork isolates, the poultry meat isolates had a greater percentage of resistance to all tested drugs, with the exception of chloramphenicol, to which pork isolates had the most resistance. More than half of the turkey isolates (56%) were resistant to multidrugs (≥3 classes) compared to 38.9% of chicken, 17.3% of pork, and 9.3% of beef isolates. The blaCMY gene was present in all ceftriaxone- and ceftiofur-resistant isolates. The cmlA, flo, and catI genes were present in 45%, 43%, and 40% of chloramphenicol-resistant isolates, respectively. Most nalidixic acid-resistant isolates (98.5%) had a gyrA mutation in S83 or D87 or both, whereas only 6.7% had a parC mutation in either S80 or E84. The results showed that E. coli was commonly present in the retail meats, and antimicrobial resistance profiles differed according to the animal origin of the isolates.",
"title": "Comparison of the Prevalences and Antimicrobial Resistances of Escherichia coli Isolates from Different Retail Meats in the United States, 2002 to 2008"
},
{
"docid": "MED-3892",
"text": "Mathematical models that estimate the proportion of foodborne illnesses attributable to food commodities at specific points in the food chain may be useful to risk managers and policy makers to formulate public health goals, prioritize interventions, and document the effectiveness of mitigations aimed at reducing illness. Using human surveillance data on laboratory-confirmed Salmonella infections from the Centers for Disease Control and Prevention and Salmonella testing data from U.S. Department of Agriculture Food Safety and Inspection Service's regulatory programs, we developed a point-of-processing foodborne illness attribution model by adapting the Hald Salmonella Bayesian source attribution model. Key model outputs include estimates of the relative proportions of domestically acquired sporadic human Salmonella infections resulting from contamination of raw meat, poultry, and egg products processed in the United States from 1998 through 2003. The current model estimates the relative contribution of chicken (48%), ground beef (28%), turkey (17%), egg products (6%), intact beef (1%), and pork (<1%) across 109 Salmonella serotypes found in food commodities at point of processing. While interpretation of the attribution estimates is constrained by data inputs, the adapted model shows promise and may serve as a basis for a common approach to attribution of human salmonellosis and food safety decision-making in more than one country.",
"title": "Application of Bayesian Techniques to Model the Burden of Human Salmonellosis Attributable to U.S. Food Commodities at the Point of Processing: Adaptation of a Danish Model"
}
] |
[
{
"docid": "MED-5251",
"text": "Dietary habits have been rarely associated with seizure frequency in patients with epilepsy. We report a case of a man with a partial symptomatic epilepsy whose daily habit of heavy coffee drinking was associated with an increased seizure frequency. This patient witnessed a dramatic decrease in the frequency of his seizures after stopping coffee ingestion. Caffeine is a global stimulant and the reduction of its intake may help in the treatment of epilepsy.",
"title": "Heavy coffee drinking and epilepsy."
},
{
"docid": "MED-3178",
"text": "Neurocysticercosis (NCC) is the most frequent parasitic disease of the human brain. Modern imaging studies, CT and MRI, have defined the diagnosis and characterization of the disease. Through these studies the therapeutic approach for each case may be individualized with the aid of antihelmintics, steroids, symptomatic medicines, or surgery. The use of one or various therapeutic measures largely depends on the peculiar combination of number, location, and biological stage of lesions as well as the degree of inflammatory response to the parasites. Although there is not a typical clinical picture of NCC, epilepsy is the most frequent manifestation of parenchymal NCC, whereas hydrocephalus is the most frequent manifestation of meningeal NCC. Eradication of cysticercosis is an attainable goal by public education and sanitary improvement in endemic areas.",
"title": "Clinical manifestations, diagnosis, and treatment of neurocysticercosis."
},
{
"docid": "MED-301",
"text": "Epilepsy or seizure disorder is one of the most common neurological diseases in humans. Although genetic mutations in ion channels and receptors and some other risk factors such as brain injury are linked to epileptogenesis, the underlying cause for the majority of epilepsy cases remains unknown. Gene-environment interactions are thought to play a critical role in the etiology of epilepsy. Exposure to environmental chemicals is an important risk factor. Methylmercury (MeHg) is a prominent environmental neurotoxicant, which targets primarily the central nervous system (CNS). Patients or animals with acute or chronic MeHg poisoning often display epileptic seizures or show increased susceptibility to seizures, suggesting that MeHg exposure may be associated with epileptogenesis. This mini-review highlights the effects of MeHg exposure, especially developmental exposure, on the susceptibility of humans and animals to seizures, and discusses the potential role of low level MeHg exposure in epileptogenesis. This review also proposes that a preferential effect of MeHg on the inhibitory GABAergic system, leading to disinhibition of excitatory glutamatergic function, may be one of the potential mechanisms underlying MeHg-induced changes in seizure susceptibility.",
"title": "Methylmercury: A Potential Environmental Risk Factor Contributing to Epileptogenesis"
},
{
"docid": "MED-3170",
"text": "Background Few studies have focused on the cognitive morbidity of neurocysticercosis (NCC), one of the most common parasitic infections of the central nervous system. We longitudinally assessed the cognitive status and quality of life (QoL) of patients with incident symptomatic NCC cases and matched controls. Methodology/Principal Findings The setting of the study was the Sabogal Hospital and Cysticercosis Unit, Department of Transmissible Diseases, National Institute of Neurological Sciences, Lima, Peru. The design was a longitudinal study of new onset NCC cases and controls. Participants included a total of 14 patients with recently diagnosed NCC along with 14 healthy neighborhood controls and 7 recently diagnosed epilepsy controls. A standardized neuropsychological battery was performed at baseline and at 6 months on NCC cases and controls. A brain MRI was performed in patients with NCC at baseline and 6 months. Neuropsychological results were compared between NCC cases and controls at both time points. At baseline, patients with NCC had lower scores on attention tasks (p<0.04) compared with epilepsy controls but no significant differences compared to healthy controls. Six months after receiving anti-parasitic treatment, the NCC group significantly improved on tasks involving psychomotor speed (p<0.02). QoL at baseline suggested impaired mental function and social function in both the NCC and epilepsy group compared with healthy controls. QoL gains in social function (p = 0.006) were noted at 6 months in patients with NCC. Conclusions/Significance Newly diagnosed patients with NCC in this sample had mild cognitive deficits and more marked decreases in quality of life at baseline compared with controls. Improvements were found in both cognitive status and quality of life in patients with NCC after treatment. Author Summary Neurocysticercosis (NCC) is one of the most common parasitic infections of the central nervous system. Cognitive changes have been frequently reported with this disease but have not been well studied. Our study team recruited a group of new onset NCC cases and a matched set of healthy neighborhood controls and new onset epilepsy controls in Lima, Peru for this study. A neuropsychological battery was administered at baseline and at 6 months to all groups. Brain MRI studies were also obtained on NCC cases at baseline and at 6 months. Newly diagnosed patients with NCC had mild cognitive deficits and more marked decreases in quality of life at baseline compared with controls. Improvements were found in both cognitive status and quality of life in patients with NCC after treatment. This study is the first to assess cognitive status and quality of life longitudinally in patients with NCC and provides new data on an important clinical morbidity outcome.",
"title": "Cognitive Changes and Quality of Life in Neurocysticercosis: A Longitudinal Study"
},
{
"docid": "MED-4391",
"text": "Cancer is a leading cause of death worldwide. There are a lot of cancer causing agents which are divided as physical carcinogens, chemical carcinogens and biological carcinogens. But most of the carcinogens or causes of cancer are related to our lifestyle like diet, habit, occupation, radiation and some infection, etc. Chemoprevention is highly necessary to prevent cancer related preterm death. For this besides avoiding the causes of cancer we should concentrate ourselves on our diet. Because, numerous phytochemicals derived from edible plants have been reported to interfere with a specific stage of the carcinogenic process. Many mechanisms have been shown to account for the anticarcinogenic actions of dietary constituents and recently attention has been focused on intracellular-signalling cascades as common molecular targets for various chemopreventive phytochemicals. In this study, we tried to describe lifestyle related causes of cancer and the molecular basis of cancer prevention through the phytochemicals.",
"title": "Lifestyle related causes of cancer and chemoprevention through phytonutrients."
},
{
"docid": "MED-3527",
"text": "BACKGROUND: : Jet-lag commonly affects air travellers who cross several time zones. It results from the body's internal rhythms being out of step with the day-night cycle at the destination. Melatonin is a pineal hormone that plays a central part in regulating bodily rhythms and has been used as a drug to re-align them with the outside world. OBJECTIVES: : To assess the effectiveness of oral melatonin taken in different dosage regimens for alleviating jet-lag after air travel across several time zones. SEARCH STRATEGY: : We searched the Cochrane Controlled Trials Register, MEDLINE, EMBASE, PsychLit and Science Citation Index electronically, and the journals 'Aviation, Space and Environmental Medicine' and 'Sleep' by hand. We searched citation lists of relevant studies for other relevant trials. We asked principal authors of relevant studies to tell us about unpublished trials. Reports of adverse events linked to melatonin use outside randomised trials were searched for systematically in 'Side Effects of Drugs' (SED) and SED Annuals, 'Reactions Weekly', MEDLINE, and the adverse drug reactions databases of the WHO Uppsala Monitoring Centre (UMC) and the US Food & Drug Administration. SELECTION CRITERIA: : Randomised trials in airline passengers, airline staff or military personnel given oral melatonin, compared with placebo or other medication. Outcome measures should consist of subjective rating of jet-lag or related components, such as subjective wellbeing, daytime tiredness, onset and quality of sleep, psychological functioning, duration of return to normal, or indicators of circadian rhythms. DATA COLLECTION AND ANALYSIS: : Ten trials met the inclusion criteria. All compared melatonin with placebo; one in addition compared it with a hypnotic, zolpidem. Nine of the trials were of adequate quality to contribute to the assessment, one had a design fault and could not be used in the assessment. Reports of adverse events outside trials were found through MEDLINE, 'Reactions Weekly', and in the WHO UMC database. MAIN RESULTS: : Nine of the ten trials found that melatonin, taken close to the target bedtime at the destination (10pm to midnight), decreased jet-lag from flights crossing five or more time zones. Daily doses of melatonin between 0.5 and 5mg are similarly effective, except that people fall asleep faster and sleep better after 5mg than 0.5mg. Doses above 5mg appear to be no more effective. The relative ineffectiveness of 2mg slow-release melatonin suggests that a short-lived higher peak concentration of melatonin works better. Based on the review, the number needed to treat (NNT) is 2. The benefit is likely to be greater the more time zones are crossed, and less for westward flights. The timing of the melatonin dose is important: if it is taken at the wrong time, early in the day, it is liable to cause sleepiness and delay adaptation to local time. The incidence of other side effects is low. Case reports suggest that people with epilepsy, and patients taking warfarin may come to harm from melatonin. REVIEWER'S CONCLUSIONS: : Melatonin is remarkably effective in preventing or reducing jet-lag, and occasional short-term use appears to be safe. It should be recommended to adult travellers flying across five or more time zones, particularly in an easterly direction, and especially if they have experienced jet-lag on previous journeys. Travellers crossing 2-4 time zones can also use it if need be. The pharmacology and toxicology of melatonin needs systematic study, and routine pharmaceutical quality control of melatonin products must be established. The effects of melatonin in people with epilepsy, and a possible interaction with warfarin, need investigation.",
"title": "Melatonin for the prevention and treatment of jet lag."
},
{
"docid": "MED-3204",
"text": "Grapefruit is a healthy addition to a well-balanced diet. However, the fruit has been shown to affect the metabolism of many medications, increasing the risk of toxicity and adverse effects. Characteristics of oral medications that may interact with grapefruit include extensive metabolism through the intestinal cytochrome P450 3A4 system, low bioavailability, and a narrow therapeutic index. Prominent medications known to interact with grapefruit include statins, antiarrhythmic agents, immunosuppressive agents, and calcium channel blockers. There are equally effective alternatives to these drug classes that do not have the potential to interact with grapefruit. These alternative drugs may be substituted if a patient experiences or is at risk of a grapefruit-drug interaction. Patients also may choose to exclude grapefruit from their diets and consume other fruits, including other types of citrus, to avoid an interaction.",
"title": "Management of grapefruit-drug interactions."
},
{
"docid": "MED-1679",
"text": "BACKGROUND: Healthy lifestyle choices such as eating a prudent diet, exercising regularly, managing weight, and not smoking may substantially reduce coronary heart disease (CHD) risk by improving lipids, blood pressure, and other risk factors. The burden of CHD that could be avoided through adherence to these modifiable lifestyle factors has not been assessed among middle-aged and older US men, specifically men taking medications for hypertension or hypercholesterolemia. METHODS AND RESULTS: We prospectively monitored 42 847 men in the Health Professionals Follow-up Study, 40 to 75 years of age and free of disease in 1986. Lifestyle factors were updated through self-reported questionnaires. Low risk was defined as (1) absence of smoking, (2) body mass index <25 kg/m2, (3) moderate-to-vigorous activity > or = 30 min/d, (4) moderate alcohol consumption (5 to 30 g/d), and (5) the top 40% of the distribution for a healthy diet score. Over 16 years, we documented 2183 incident cases of CHD (nonfatal myocardial infarction and fatal CHD). In multivariate-adjusted Cox proportional hazards models, men who were at low risk for 5 lifestyle factors had a lower risk of CHD (relative risk: 0.13; 95% confidence interval [CI]: 0.09, 0.19) compared with men who were at low risk for no lifestyle factors. Sixty-two percent (95% CI: 49%, 74%) of coronary events in this cohort may have been prevented with better adherence to these 5 healthy lifestyle practices. Among men taking medication for hypertension or hypercholesterolemia, 57% (95% CI: 32%, 79%) of all coronary events may have been prevented with a low-risk lifestyle. Compared with men who did not make lifestyle changes during follow-up, those who adopted > or = 2 additional low-risk lifestyle factors had a 27% (95% CI: 7%, 43%) lower risk of CHD. CONCLUSIONS: A majority of CHD events among US men may be preventable through adherence to healthy lifestyle practices, even among those taking medications for hypertension or hypercholesterolemia.",
"title": "Healthy lifestyle factors in the primary prevention of coronary heart disease among men: benefits among users and nonusers of lipid-lowering and an..."
},
{
"docid": "MED-2437",
"text": "BACKGROUND: Breast cancer is the most commonly diagnosed cancer among women in the United States. Extensive research has been completed to evaluate the relationship between dietary factors and breast cancer risk and survival after breast cancer; however, a summary report with clinical inference is needed. Materials and METHODS: This review summarizes the current epidemiological and clinical trial evidence relating diet to breast cancer incidence, recurrence, survival, and mortality. The review includes emerging epidemiological studies that assess risk within breast cancer subtypes as well as a summary of previous and ongoing dietary intervention trials designed to modify breast cancer risk. RESULTS: The available literature suggests that both low-fat and high-fiber diets may be weakly protective against breast cancer, whereas total energy intake and alcohol appear to be positively associated. Fiber may be weakly protective possibly through modulation of estrogen, whereas fruit and vegetable intake is not clearly associated with risk. Obesity is a risk factor for postmenopausal disease, and adult weight gain should be avoided to reduce risk. In survivors, diet has the greatest potential influence on overall mortality rather than breast cancer-specific events. CONCLUSION: Diet is modestly associated with breast cancer risk; associations appear more pronounced for postmenopausal disease, and healthy choices after diagnosis and treatment likely support longevity more so than reduced risk for recurrent disease.",
"title": "Diet and breast cancer: understanding risks and benefits."
},
{
"docid": "MED-2527",
"text": "BACKGROUND: One of the major issues in controlling serum cholesterol through dietetic intervention appears to be the need to improve patient adherence. AIMS: To explore the many questions regarding barriers to, and motivators for, cholesterol-lowering diet adherence. METHODS: We surveyed French general practitioners' dietetic practices for patients with hypercholesterolaemia, and looked at their patients' attitudes towards such an approach. RESULTS: We analysed 234 doctors' personal questionnaires and 356 patient self-survey questionnaires. Patients' reasons for not complying with the prescribed diet included: 'already having satisfactory food habits' (34.7%), 'unwillingness to suffer nutritional deprivation' (33.3%), 'difficulties to conciliate a diet with family life' (27.8%) and 'taking cholesterol-lowering drugs' (22.2%). Despite a generally good understanding by patients of doctors' recommendations, some discrepancies were seen between their respective declarations. While doctors largely thought that patients needed more explanation on why and how a diet can lower cholesterol (and avoid taking drugs), only 39.4% of patients declared needing this kind of information. Other discrepancies were observed concerning barriers to, and motivators for, patient adherence. Moreover, some dietetic rules appeared to be more difficult to comply with than others, e.g. 82.6% patients remembered they should 'eat more fish' but only 51.3% actually did so. Finally, physicians, as well as patients, displayed a lack of confidence in lipid-lowering diet efficiency. CONCLUSION: Improving patient education, especially concerning their perception of risk, as well as increasing the involvement of dieticians, are motivators to explore in order to improve adherence. Copyright © 2012 Elsevier Masson SAS. All rights reserved.",
"title": "Cross-analysis of dietary prescriptions and adherence in 356 hypercholesterolaemic patients."
},
{
"docid": "MED-4451",
"text": "Research leading to the discovery of a series of mutagenic and carcinogenic heterocyclic amines (HCAs) was inspired by the idea that smoke produced during cooking of food, especially meat or fish, might be carcinogenic. More than ten kinds of HCAs, actually produced by cooking or heating of meat or fish, have now been isolated and their structures determined, most being previously unregistered compounds. They are highly mutagenic towards Salmonella typhimurium in the presence of S9 mix and are also mutagenic in vitro and in vivo toward mammalian cells. HCAs have now been chemically synthesized in quantity and subjected to long-term animal testing. When HCAs were fed in the diet, rodents developed cancers in many organs, including the colon, breast and prostate, and one HCA produced hepatomas in monkeys. The lesions exhibited alteration in genes including Apc, beta-catenin and Ha-ras, and these changes provide clues to the induction mechanisms. The HCAs are oxidized to hydroxyamino derivatives by cytochrome P450s, and further converted to ester forms by acetyltransferase and sulfotransferase. Eventually, they produce DNA adducts through the formation of N-C bonds at guanine bases. There are HCA-sensitive and resistant strains of rodents and a search for the responsible genes is now under way. While the content of HCAs in dishes consumed in ordinary life is low and not sufficient in itself to explain human cancer, the coexistence of many other mutagens/carcinogens of either autobiotic or xenobiotic type and the possibility that HCAs induce genomic instability and heightened sensitivity to tumor promoters suggest that avoidance of exposure to HCAs or reduction of HCAs' biological effects as far as possible are to be highly recommended. Usage of microwave ovens for cooking and supplementation of the diet, for example with soy-isoflavones, which have been found to suppress the occurrence of HCA-induced breast cancers, should be encouraged. Advice to the general public about how to reduce the carcinogenic load imposed by HCAs would be an important contribution to cancer prevention.",
"title": "Heterocyclic amines: Mutagens/carcinogens produced during cooking of meat and fish."
},
{
"docid": "MED-1748",
"text": "Our bloodstream is considered to be an environment well separated from the outside world and the digestive tract. According to the standard paradigm large macromolecules consumed with food cannot pass directly to the circulatory system. During digestion proteins and DNA are thought to be degraded into small constituents, amino acids and nucleic acids, respectively, and then absorbed by a complex active process and distributed to various parts of the body through the circulation system. Here, based on the analysis of over 1000 human samples from four independent studies, we report evidence that meal-derived DNA fragments which are large enough to carry complete genes can avoid degradation and through an unknown mechanism enter the human circulation system. In one of the blood samples the relative concentration of plant DNA is higher than the human DNA. The plant DNA concentration shows a surprisingly precise log-normal distribution in the plasma samples while non-plasma (cord blood) control sample was found to be free of plant DNA.",
"title": "Complete Genes May Pass from Food to Human Blood"
},
{
"docid": "MED-3545",
"text": "Background Omnivorous diets are high in arachidonic acid (AA) compared to vegetarian diets. Research shows that high intakes of AA promote changes in brain that can disturb mood. Omnivores who eat fish regularly increase their intakes of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), fats that oppose the negative effects of AA in vivo. In a recent cross-sectional study, omnivores reported significantly worse mood than vegetarians despite higher intakes of EPA and DHA. This study investigated the impact of restricting meat, fish, and poultry on mood. Findings Thirty-nine omnivores were randomly assigned to a control group consuming meat, fish, and poultry daily (OMN); a group consuming fish 3-4 times weekly but avoiding meat and poultry (FISH), or a vegetarian group avoiding meat, fish, and poultry (VEG). At baseline and after two weeks, participants completed a food frequency questionnaire, the Profile of Mood States questionnaire and the Depression Anxiety and Stress Scales. After the diet intervention, VEG participants reduced their EPA, DHA, and AA intakes, while FISH participants increased their EPA and DHA intakes. Mood scores were unchanged for OMN or FISH participants, but several mood scores for VEG participants improved significantly after two weeks. Conclusions Restricting meat, fish, and poultry improved some domains of short-term mood state in modern omnivores. To our knowledge, this is the first trial to examine the impact of restricting meat, fish, and poultry on mood state in omnivores.",
"title": "Restriction of meat, fish, and poultry in omnivores improves mood: A pilot randomized controlled trial"
},
{
"docid": "MED-1552",
"text": "OBJECTIVE: To determine the quantitative importance of dietary fatty acids and dietary cholesterol to blood concentrations of total, low density lipoprotein, and high density lipoprotein cholesterol. DESIGN: Meta-analysis of metabolic ward studies of solid food diets in healthy volunteers. SUBJECTS: 395 dietary experiments (median duration 1 month) among 129 groups of individuals. RESULTS: Isocaloric replacement of saturated fats by complex carbohydrates for 10% of dietary calories resulted in blood total cholesterol falling by 0.52 (SE 0.03) mmol/l and low density lipoprotein cholesterol falling by 0.36 (0.05) mmol/l. Isocaloric replacement of complex carbohydrates by polyunsaturated fats for 5% of dietary calories resulted in total cholesterol falling by a further 0.13 (0.02) mmol/l and low density lipoprotein cholesterol falling by 0.11 (0.02) mmol/l. Similar replacement of carbohydrates by monounsaturated fats produced no significant effect on total or low density lipoprotein cholesterol. Avoiding 200 mg/day dietary cholesterol further decreased blood total cholesterol by 0.13 (0.02) mmol/l and low density lipoprotein cholesterol by 0.10 (0.02) mmol/l. CONCLUSIONS: In typical British diets replacing 60% of saturated fats by other fats and avoiding 60% of dietary cholesterol would reduce blood total cholesterol by about 0.8 mmol/l (that is, by 10-15%), with four fifths of this reduction being in low density lipoprotein cholesterol.",
"title": "Dietary lipids and blood cholesterol: quantitative meta-analysis of metabolic ward studies."
},
{
"docid": "MED-5134",
"text": "This position paper on complementary feeding summarizes evidence for health effects of complementary foods. It focuses on healthy infants in Europe. After reviewing current knowledge and practices, we have formulated these conclusions: Exclusive or full breast-feeding for about 6 months is a desirable goal. Complementary feeding (ie, solid foods and liquids other than breast milk or infant formula and follow-on formula) should not be introduced before 17 weeks and not later than 26 weeks. There is no convincing scientific evidence that avoidance or delayed introduction of potentially allergenic foods, such as fish and eggs, reduces allergies, either in infants considered at increased risk for the development of allergy or in those not considered to be at increased risk. During the complementary feeding period, >90% of the iron requirements of a breast-fed infant must be met by complementary foods, which should provide sufficient bioavailable iron. Cow's milk is a poor source of iron and should not be used as the main drink before 12 months, although small volumes may be added to complementary foods. It is prudent to avoid both early (<4 months) and late (>or=7 months) introduction of gluten, and to introduce gluten gradually while the infant is still breast-fed, inasmuch as this may reduce the risk of celiac disease, type 1 diabetes mellitus, and wheat allergy. Infants and young children receiving a vegetarian diet should receive a sufficient amount ( approximately 500 mL) of breast milk or formula and dairy products. Infants and young children should not be fed a vegan diet.",
"title": "Complementary feeding: a commentary by the ESPGHAN Committee on Nutrition."
},
{
"docid": "MED-3181",
"text": "OBJECTIVE: To determine the frequency and features of psychiatric morbidity in a cross section of 38 outpatients with neurocysticercosis. METHODS: Diagnosis of neurocysticercosis was established by CT, MRI, and CSF analysis. Psychiatric diagnoses were made by using the present state examination and the schedule for affective disorders and schizophrenia-lifetime version; cognitive state was assessed by mini mental state examination and Strub and Black's mental status examination. RESULTS: Signs of psychiatric disease and cognitive decline were found in 65.8 and 87.5% of the cases respectively. Depression was the most frequent psychiatric diagnosis (52.6%) and 14.2% of the patients were psychotic. Active disease and intracranial hypertension were associated with higher psychiatric morbidity, and previous history of mood disorders was strongly related to current depression. Other variables, such as number and type of brain lesions, severity of neuropsychological deficits, epilepsy, and use of steroids did not correlate with mental disturbances in this sample. CONCLUSIONS: Psychiatric abnormalities, particularly depression syndromes, are frequent in patients with neurocysticercosis. Although regarded as a rare cause of dementia, mild cognitive impairment may be a much more prevalent neuropsychological feature of patients with neurocysticercosis. The extent to which organic mechanisms related to brain lesions may underlie the mental changes is yet unclear, although the similar sex distribution of patients with and without depression, as well as the above mentioned correlations, provide further evidence of the part played by organic factors in the cause of these syndromes.",
"title": "Psychiatric manifestations of neurocysticercosis: a study of 38 patients from a neurology clinic in Brazil."
},
{
"docid": "MED-2014",
"text": "BACKGROUND: Gastrointestinal symptoms that respond to the removal of wheat and/or gluten are becoming more common. Patients who avoid wheat and/or gluten (PWAWG) are a heterogeneous group and predominantly self-diagnosed prior to presenting for clinical evaluation. SPECIFIC AIM: We characterized PWAWGs seen at a tertiary care referral center and compared them to patients with celiac disease (CD) and subjects in the National Health and Nutrition examination survey (NHANES). METHODS: This was a cross-sectional study evaluating patients seen by four gastroenterologists at a CD referral center. Baseline characteristics, laboratory values, and medical comorbidities were compared to CD patients who presented at the same center and subjects enrolled in NHANES. RESULTS: Eighty-four PWAWGs were identified and compared to 585 CD patients and 2,686 NHANES patients. Thirty-two alternative diagnoses were made in 25 (30%) PWAWGs, including small intestinal bacterial overgrowth and fructose/lactose intolerance. When compared to patients with CD, PWAWGs had similar body mass index (BMI, 23.1 vs. 23.5, p = 0.54) and mean hemoglobin value (13.4 vs. 13.3, p = 0.6). When compared to male and female patients in NHANES, BMI, folate, and mean hemoglobin values were lower in PWAWGs. Both male and female PWAWGs had a lower prevalence of hypertension. CONCLUSION: While there are similarities between CD and PWAWGs that could possibly be due to shared HLA haplotypes or an effect of the gluten-free diet, alternative diagnoses are common in these patients. PWAWGs have a similar cardiovascular profile as CD patients in terms of lower BMI and lower prevalence of hypertension.",
"title": "Characteristics of patients who avoid wheat and/or gluten in the absence of Celiac disease."
},
{
"docid": "MED-1595",
"text": "Hormones work in harmony in the body, and this status must be maintained to avoid metabolic disequilibrium and the subsequent illness. Besides, it has been reported that exogenous steroids (presence in the environment and food products) influence the development of several important illnesses in humans. Endogenous steroid hormones in food of animal origin are unavoidable as they occur naturally in these products. The presence of hormones in food has been connected with several human health problems. Bovine milk contains considerable quantities of hormones and it is of particular concern. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, based on hydroxylamine derivatisation, has been developed and validated for the quantification of six sex hormones in milk [pregnenolone (P₅), progesterone (P₄), estrone (E₁), testosterone (T), androstenedione (A) and dehydroepiandrosterone (DHEA)]. This method has been applied to real raw milk samples and the existence of differences between milk from pregnant and non-pregnant cows has been statistically confirmed. Basing on a revision of existing published data, it could be concluded that maximum daily intakes for hormones are not reached through milk ingestion. Although dairy products are an important source of hormones, other products of animal origin must be considered as well for intake calculations.",
"title": "Development of an LC-MS/MS method to quantify sex hormones in bovine milk and influence of pregnancy in their levels."
},
{
"docid": "MED-3154",
"text": "Anecdotal, survey, and epidemiological data suggest that endurance athletes are at an increased risk for upper respiratory tract infection (URTI) during periods of heavy training and the 1 - to 2-wk period after race events. The majority of athletes, however, who participate in endurance race events do not experience illness. Of greater public health importance is the consistent finding of a reduction in URTI risk reported by fitness enthusiasts and athletes who engage in regular exercise training while avoiding overreaching/overtraining. Although it naturally follows that infection risk should in some way be linked to acute and chronic exercise-induced alterations in immunity, attempts thus far to measure this association have been unsuccessful. There is growing evidence that for several hours subsequent to heavy exertion, several components of both the innate and adaptive immune system exhibit suppressed function. The immune response to heavy exertion is transient, however, and further research on the mechanisms underlying the immune response to prolonged and intensive endurance exercise is necessary before meaningful clinical applications can be drawn. Some attempts have been made through chemical or nutritional means (e.g., indomethacin, glutamine, vitamin C, and carbohydrate supplementation) to attenuate immune changes after intensive exercise to lower the risk of infection. No consistent relationship between nutritional interventions, exercise immunology, and alteration in URTI risk has yet been established.",
"title": "Is infection risk linked to exercise workload?"
},
{
"docid": "MED-3179",
"text": "OBJECTIVES: Neurocysticercosis (NCYST) is the most frequent CNS parasitic disease worldwide, affecting more than 50 million people. However, some of its clinical findings, such as cognitive impairment and dementia, remain poorly characterized, with no controlled studies conducted so far. We investigated the frequency and the clinical profile of cognitive impairment and dementia in a sample of patients with NCYST in comparison with cognitively healthy controls (HC) and patients with cryptogenic epilepsy (CE). METHODS: Forty treatment-naive patients with NCYST, aged 39.25 +/- 10.50 years and fulfilling absolute criteria for definitive active NCYST on MRI, were submitted to a comprehensive cognitive and functional evaluation and were compared with 49 HC and 28 patients with CE of similar age, educational level, and seizure frequency. RESULTS: Patients with NCYST displayed significant impairment in executive functions, verbal and nonverbal memory, constructive praxis, and verbal fluency when compared with HC (p < 0.05). Dementia was diagnosed in 12.5% patients with NCYST according to DSM-IV criteria. When compared with patients with CE, patients with NCYST presented altered working and episodic verbal memory, executive functions, naming, verbal fluency, constructive praxis, and visual-spatial orientation. No correlation emerged between cognitive scores and number, localization, or type of NCYST lesions on MRI. CONCLUSIONS: Cognitive impairment was ubiquitous in this sample of patients with active neurocysticercosis (NCYST). Antiepileptic drug use and seizure frequency could not account for these features. Dementia was present in a significant proportion of patients. These data broaden our knowledge on the clinical presentations of NCYST and its impact in world public health.",
"title": "Cognitive impairment and dementia in neurocysticercosis: a cross-sectional controlled study."
},
{
"docid": "MED-4972",
"text": "Heterocyclic amines (HCAs), compounds formed when meat is cooked at high temperatures particularly through pan frying, grilling, or barbequing, pose a potential carcinogenic risk to the public. It is unclear whether there is any level at which consumption of HCAs can be considered safe. Efforts to measure these compounds mainly include cooking studies under laboratory conditions and some measurement of home-cooked foods, but analysis of commercially cooked foods has been minimal. Attempts to estimate exposure of the public to these compounds must take into consideration dining outside the home, which could result in significant exposure for some individuals. We surveyed at least 9 locations each of 7 popular chain restaurants (McDonald's, Burger King, Chick-fil-A, Chili's, TGI Friday's, Outback Steakhouse, and Applebee's) in California, collecting one or two entrees from each location. Entrees were analyzed for 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) using high-performance liquid chromatography tandem mass spectrometry. All 100 samples contained PhIP. Concentrations were variable within and between entrees and ranged from 0.08 to 43.2 ng/g. When factoring in the weight of the entrees, absolute levels of PhIP reached over 1,000 ng for some entrees. Potential strategies for reducing exposure include the avoidance of meats cooked using methods that are known to form PhIP.",
"title": "Detection of PhIP in grilled chicken entrées at popular chain restaurants throughout California."
},
{
"docid": "MED-5133",
"text": "We report the case of a 7 month-old girl that presented with acute anemia, generalized muscular hypotonia and failure to thrive. Laboratory evaluation revealed cobalamin deficiency, due to a vegan diet of the mother. The clinical triad of an acquired floppy baby syndrome with megaloblastic anemia and failure to thrive is pathognomic for infantile cobalamin deficiency. Neurological abnormalities are often irreversible and may be associated with delayed myelinization in the MRI. A normal cobalamin level in maternal serum and absence of anemia do not exclude subclinical deficiency. If cobalamin deficiency is suspected, e.g. in pregnant women on vegan diet, urinary methylmalonic acid excretion and plasma homocysteine levels should be determined and cobalamin substitution should be started at an early stage to avoid potentially irreversible damage of the fetus.",
"title": "[Floppy baby with macrocytic anemia and vegan mother]."
},
{
"docid": "MED-1851",
"text": "The brain is a highly compartmentalized organ exceptionally susceptible to accumulation of metabolic errors. Alzheimer's disease (AD) is the most prevalent neurodegenerative disease of the elderly and is characterized by regional specificity of neural aberrations associated with higher cognitive functions. Aluminum (Al) is the most abundant neurotoxic metal on earth, widely bioavailable to humans and repeatedly shown to accumulate in AD-susceptible neuronal foci. In spite of this, the role of Al in AD has been heavily disputed based on the following claims: 1) bioavailable Al cannot enter the brain in sufficient amounts to cause damage, 2) excess Al is efficiently excreted from the body, and 3) Al accumulation in neurons is a consequence rather than a cause of neuronal loss. Research, however, reveals that: 1) very small amounts of Al are needed to produce neurotoxicity and this criterion is satisfied through dietary Al intake, 2) Al sequesters different transport mechanisms to actively traverse brain barriers, 3) incremental acquisition of small amounts of Al over a lifetime favors its selective accumulation in brain tissues, and 4) since 1911, experimental evidence has repeatedly demonstrated that chronic Al intoxication reproduces neuropathological hallmarks of AD. Misconceptions about Al bioavailability may have misled scientists regarding the significance of Al in the pathogenesis of AD. The hypothesis that Al significantly contributes to AD is built upon very solid experimental evidence and should not be dismissed. Immediate steps should be taken to lessen human exposure to Al, which may be the single most aggravating and avoidable factor related to AD.",
"title": "Aluminum and Alzheimer's disease: after a century of controversy, is there a plausible link?"
},
{
"docid": "MED-3523",
"text": "Melatonin, which is contained in certain vegetables, may have an influence on circulatory melatonin concentrations. This study examined the effects of the consumption of vegetables on 6-sulfatoxymelatonin concentrations in morning urine. Ninety-four healthy women aged 24-55 were recruited through a city public health center in Japan. The women randomly allocated to the intervention group were requested to consume high amounts of six selected vegetables, with a target of 350 g/day for 65 days, while those in the control group were asked to avoid the same six vegetables during the same period. First-void morning urine was collected before and at the end of the intervention period, and creatinine-adjusted 6-sulfatoxymelatonin concentrations were measured. At the end of the intervention period, daily mean intake of melatonin from the six vegetables was 1288.0 ng in the intervention group and 5.3 ng in the control group. In the intervention group, the mean concentration of 6-sulfatoxymelatonin changed from 48.1 [95% confidence interval (CI): 40.4-57.2] ng/mg creatinine to 49.6 (95% CI: 42.8-57.3) ng/mg creatinine across the intervention period. In the control group, the mean concentration of 6-sulfatoxymelatonin changed from 55.5 (95% CI: 48.7-63.2) ng/mg creatinine to 50.8 (95% CI: 44.0-58.7) ng/mg creatinine across the intervention period. A comparison of the two groups with regard to the changes in the 6-sulfatoxymelatonin concentrations across the intervention period showed a significant difference (P = 0.03). The results indicate that increased consumption of vegetables raises circulatory melatonin concentrations.",
"title": "Consumption of vegetables alters morning urinary 6-sulfatoxymelatonin concentration."
},
{
"docid": "MED-4511",
"text": "BACKGROUND: Pure vegetarian diets might cause cobalamin deficiency due to lack of dietary intake. It was hypothesized that a population following a vegan diet consuming mostly raw fruits and vegetables, carrot juice, and dehydrated barley grass juice would be able to avoid vitamin B12 deficiency naturally. METHODS: Subjects were recruited at a health ministers' reunion based on adherence to the Hallelujah diet for at least 2 years. Serum cobalamin and urinary methylmalonic acid (MMA) assays were performed. Follow-up with sublingual tablets, nutritional yeast, or probiotic supplements was carried out on subjects with abnormal MMA results. RESULTS: 49 subjects were tested. Most subjects (10th to 90th percentile) had followed this diet 23-49 months. 6 subjects had serum B12 concentrations <147 pmol/l (200 pg/ml). 37 subjects (76%) had serum B12 concentrations <221 pmol/l (300 pg/ml). 23 subjects (47%) had abnormal urinary MMA concentrations above or equal to 4.0 microg/mg creatinine. Sublingual cyanocobalamin and nutritional yeast, but not probiotic supplements, significantly reduced group mean MMA concentrations (tablet p < 0.01; yeast p < 0.05, probiotic > 0.20). CONCLUSIONS: The urinary MMA assay is effective for identifying early metabolic cobalamin deficiency. People following the Hallelujah diet and other raw-food vegetarian diets should regularly monitor their urinary MMA levels, consume a sublingual cobalamin supplement, or consume cobalamin in their food.",
"title": "Metabolic vitamin B12 status on a mostly raw vegan diet with follow-up using tablets, nutritional yeast, or probiotic supplements."
},
{
"docid": "MED-5272",
"text": "Traditional cardiovascular risk factors are associated with endothelial dysfunction. The vascular endothelium plays a key role in local vascular tone regulation and can be modulated by dietary fat. We propose to determine the chronic effect of three diets with different fat compositions on postprandial endothelial function and inflammatory biomarkers. Twenty healthy men followed three 4-week diets in a randomised cross-over design: a Western diet, rich in saturated fat (22% SFA, 12% MUFA and 0.4% alpha-linolenic acid (ALA), all fractions are % of energy); a Mediterranean diet, rich in MUFA ( < 10 % SFA, 24 % MUFA and 0.4% ALA); a low-fat diet enriched in ALA ( < 10% SFA, 12% MUFA and 2% ALA). At the end of each dietary period all subjects underwent a postprandial study. Plasma concentrations of lipid parameters, soluble intercellular cell-adhesion molecule-1, soluble vascular cell-adhesion molecule-1 (sVCAM-1), nitrates and nitrites (NOx) and endothelial function studied by laser Doppler were examined at 0, 2, 4, 6 and 8 h. The endothelium-dependent vasodilatory response was greater 4 h after the ingestion of the MUFA-rich diet than after the SFA or ALA low-fat diets (P = 0.031). The 4 h postprandial plasma sVCAM-1 levels were lower after the MUFA meals than after the ALA low-fat diet (P = 0.043). The bioavailability of NOx was higher following the MUFA diet than after the SFA and ALA low-fat diets (P = 0.027). We found no differences in the other parameters measured. Chronic ingestion of a Mediterranean diet avoids the postprandial deterioration of endothelial function associated with Westernised diets in healthy individuals.",
"title": "Chronic effects of a high-fat diet enriched with virgin olive oil and a low-fat diet enriched with alpha-linolenic acid on postprandial endothelial..."
},
{
"docid": "MED-1333",
"text": "New epidemiology confirms that glucose intolerance is a risk factor for pancreatic cancer, and that this association cannot be accounted for by an adverse impact of early pancreatic cancer on beta cell function. Previous reports indicate that risk for pancreatic cancer is increased in adult-onset diabetics. Since streptozotocin diabetes inhibits carcinogen-mediated induction of pancreatic cancer in hamsters, the most reasonable interpretation of these findings is that insulin (or some other beta cell product) acts as a promoter for pancreatic carcinogenesis. This view is consistent with a report that human pancreatic adenocarcinomas express insulin receptors that can stimulate mitosis; an additional possibility is that high insulin levels indirectly promote pancreatic carcinogenesis by boosting effective IGF-I activity via hepatic actions. In international ecologic epidemiology, pancreatic cancer rates correlate tightly with dietary intake of animal products; this may reflect the fact that vegan diets are associated with low diurnal insulin secretion. There is also suggestive evidence that macrobiotic vegan diets, which are low in glycemic index, may increase mean survival time in pancreatic cancer. However, other types of diets associated with decreased postprandial insulin response, such as high-protein diets or 'Mediterranean' diets high in oleic acid, may also have the potential for pancreatic cancer prevention. The huge increases of age-adjusted pancreatic cancer mortality in Japan and among African-Americans during the last century imply that pancreatic cancer is substantially preventable; a low-insulin-response diet coupled with exercise training, weight control, and smoking avoidance, commendable for a great many other reasons, may slash pancreatic cancer mortality dramatically. Copyright 2001 Harcourt Publishers Ltd.",
"title": "Insulin secretion as a determinant of pancreatic cancer risk."
},
{
"docid": "MED-3177",
"text": "Neurocysticercosis (NCC) is an infection of the central nervous system (CNS) caused by the metacestode larval form of the parasite Taenia sp. Many factors can contribute to the endemic nature of cysticercosis. The inflammatory process that occurs in the tissue surrounding the parasite and/or distal from it can result from several associated mechanisms and may be disproportionate with the number of cysts. This discrepancy may lead to difficulty with the proper diagnosis in people from low endemic regions or regions that lack laboratory resources. In the CNS, the cysticerci have two basic forms, isolated cysts (Cysticercus cellulosae=CC) and racemose cysts (Cysticercus racemosus=CR), and may be meningeal, parenchymal, or ventricular or have a mixed location. The clinical manifestations are based on two fundamental syndromes that may occur in isolation or be associated: epilepsy and intracranial hypertension. They may be asymptomatic, symptomatic or fatal; have an acute, sub-acute or chronic picture; or may be in remission or exacerbated. The cerebrospinal fluid (CSF) may be normal, even in patients with viable cysticerci, until the patients begin to exhibit the classical syndrome of NCC in the CSF, or show changes in one or more routine analysed parameters. Computed tomography (CT) and magnetic resonance imaging (MRI) have allowed non-invasive diagnoses, but can lead to false negatives. Treatment is a highly controversial issue and is characterised by individualised therapy sessions. Two drugs are commonly used, praziquantel (PZQ) and albendazole (ABZ). The choice of anti-inflammatory drugs includes steroids and dextrochlorpheniramine (DCP). Hydrocephalus is a common secondary effect of NCC. Surgical cases of hydrocephalus must be submitted to ventricle-peritoneal shunt (VPS) immediately before cysticidal treatment, and surgical extirpation of the cyst may lead to an absence of the surrounding inflammatory process. The progression of NCC may be simple or complicated, have remission with or without treatment and may exhibit symptoms that can disappear for long periods of time or persist until death. Unknown, neglected and controversial aspects of NCC, such as the impaired fourth ventricle syndrome, the presence of chronic brain oedema and psychic complaints, in addition to the lack of detectable glucose in the CSF and re-infection are discussed.",
"title": "Neurocysticercosis: the enigmatic disease."
},
{
"docid": "MED-1540",
"text": "A number of studies have evaluated the health of vegetarians. Others have studied the health effects of foods that are preferred or avoided by vegetarians. The purpose of this review is to look critically at the evidence on the health effects of vegetarian diets and to seek possible explanations where results appear to conflict. There is convincing evidence that vegetarians have lower rates of coronary heart disease, largely explained by low LDL cholesterol, probable lower rates of hypertension and diabetes mellitus, and lower prevalence of obesity. Overall, their cancer rates appear to be moderately lower than others living in the same communities, and life expectancy appears to be greater. However, results for specific cancers are much less convincing and require more study. There is evidence that risk of colorectal cancer is lower in vegetarians and in those who eat less meat; however, results from British vegetarians presently disagree, and this needs explanation. It is probable that using the label “vegetarian” as a dietary category is too broad and that our understanding will be served well by dividing vegetarians into more descriptive subtypes. Although vegetarian diets are healthful and are associated with lower risk of several chronic diseases, different types of vegetarians may not experience the same effects on health.",
"title": "Vegetarian diets: what do we know of their effects on common chronic diseases?"
},
{
"docid": "MED-4327",
"text": "Hyperphosphatemia and hyperparathyroidism, frequently observed in patients with endstage renal disease, are associated with renal osteodystrophy, organ calcification, cardiovascular disease and sudden death. Restriction of dietary protein and phosphorus is beneficial in slowing the progression of renal failure. Dietary phosphorus restriction must be prescribed at all stages of renal failure in adults. It may be achieved by decreasing protein intake and avoiding foods rich in phosphorus. An average of 60-80% of the phosphorus intake is absorbed in the gut in dialysis patients. If phosphate binders are employed, the phosphorus absorbed from the diet may be reduced to 40%. Conventional hemodialysis with a high-flux, high-efficiency dialyzer removes approximately 30 mmol (900 mg) phosphorus during each dialysis performed three times weekly. Therefore, 750 mg of phosphorus intake should be the critical value above which a positive balance of phosphorus may occur. This value corresponds to a protein diet of 45-50 g/day or 0.8 g/kg body weight/day for a 60 kg patient. Target levels should become 9.2-9.6 mg/dl for calcium, 2.5-5.5 mg/dl for phosphorus, <55 mg2/dl2 for the calcium-phosphorus product, and 100-200 pg/ml for intact parathyroid hormone.",
"title": "Phosphate restriction in diet therapy."
}
] |
5adcaa9b5542990d50227cdc
|
Who helped James Howe pen his best known children's book?
|
[
{
"docid": "507276",
"text": "Bunnicula is a children's book series written by Deborah Howe and James Howe, featuring a vampire rabbit named Bunnicula who sucks the juice out of vegetables. Alternatively, \"Bunnicula\" is the main title of the first book in the series, published by Atheneum Books in April 1979. Deborah Howe died in 1978, months before the book first saw print. The series consists of seven books, with the latest published in 2006.",
"title": ""
},
{
"docid": "7054010",
"text": "James Howe (born August 2, 1946) is an American children's writer with more than 80 juvenile and young adult fiction books to his credit. He is known best for the Bunnicula series about a vampire rabbit that sucks the juice out of vegetables.",
"title": ""
}
] |
[
{
"docid": "5499141",
"text": "Gris Grimly is the pen name of an artist and storyteller from the Los Angeles area who is best known for his darkly whimsical children's books.",
"title": ""
},
{
"docid": "33201928",
"text": "Gurney Slade (1886–1956) was the pen name for English author Stephen Bartlett, who was best known for children's books and adventure novels. His novel \"Lovers and Luggers\" was filmed by Cinesound Productions in 1937.",
"title": ""
},
{
"docid": "195313",
"text": "James Alfred \"Alf\" Wight, OBE, FRCVS (3 October 1916 – 23 February 1995), known by the pen name James Herriot, was a British veterinary surgeon and writer, who used his many years of experiences as a veterinary surgeon to write a series of books each consisting of stories about animals and their owners. He is best known for these semi-autobiographical works, beginning with \"If Only They Could Talk\" in 1970. The British television series adapted from the books is titled \"All Creatures Great and Small\".",
"title": ""
},
{
"docid": "5852415",
"text": "James \"Jim\" Moloney (born 1954) is an Australian children's author. A prolific writer whose books span an age range from seven- to seventeen-year-olds, he is best known for his young adult novels. He has been nominated and won awards for his books in the Children's Book Council of Australia Awards. His books have been translated into French, Korean, Lithuanian and Flemish/Dutch.",
"title": ""
},
{
"docid": "47830285",
"text": "Jane Thayer (the pen name of Catherine Woolley, August 11, 1904 – July 23, 2005) was an American writer. She is known best for the book \"The Puppy Who Wanted A Boy\", which became the basis of a 1980s Saturday Morning cartoon series, \"The Puppy's Further Adventures\". Jane Thayer wrote 86 books for children, many of which (\"The Blueberry Pie Elf\" and \"The Puppy Who Wanted a Boy for Christmas\") have become classics. She was so prolific that her editor suggested she publish some of her works under a pen name. Thus, Catherine authored picture books under the pen name of Jane Thayer, while writing books for older children and adults under her real name.",
"title": ""
},
{
"docid": "8855",
"text": "Theodor Seuss Geisel ( ; March 2, 1904 – September 24, 1991) was an American author, political cartoonist, poet, animator, book publisher, and artist, best known for authoring children's books under the pen name Dr. Seuss ( ). His work includes several of the most popular children's books of all time, selling over 600 million copies and being translated into more than 20 languages by the time of his death.",
"title": ""
},
{
"docid": "568208",
"text": "A Series of Unfortunate Events is a series of thirteen children's novels by Lemony Snicket, the pen name of American author Daniel Handler. The books follow the turbulent lives of Violet, Klaus, and Sunny Baudelaire. After their parents' death in a fire, the children are placed in the custody of a murderous relative, Count Olaf, who attempts to steal their inheritance and, later, orchestrates numerous disasters with the help of his accomplices as the children attempt to flee. As the plot progresses, the Baudelaires gradually confront further mysteries surrounding their family and deep conspiracies involving a secret society known as V.F.D., with connections to both Olaf and their parents. The series is narrated by Snicket, who dedicates each of his works to his deceased love interest, Beatrice, and often attempts to dissuade the reader from continuing to read the Baudelaires' story.",
"title": ""
},
{
"docid": "1256799",
"text": "James D. \"Jim\" Grant (born 29 October 1954), primarily known by his pen name Lee Child, is a British author who writes thriller novels, and is most well-known for his \"Jack Reacher\" novel series. The books follow the adventures of a former American military policeman, Jack Reacher, who wanders the United States. His first novel, \"Killing Floor\", won both the Anthony Award, and the Barry Award for Best First Novel.",
"title": ""
},
{
"docid": "1888984",
"text": "James Allen (28 November 1864 – 24 January 1912) was a British philosophical writer known for his inspirational books and poetry and as a pioneer of the self-help movement. His best known work, \"As a Man Thinketh\", has been mass-produced since its publication in 1903. It has been a source of inspiration to motivational and self-help authors.",
"title": ""
},
{
"docid": "20647290",
"text": "Alec Greven is a \"New York Times\" best-selling child self-help author. His first book, \"How to Talk to Girls\", was published when he was nine years old. He has subsequently published two additional books, \"How to Talk to Moms\" and \"How to Talk to Dads\". He released his fourth book, \"How to Talk to Santa\", in 2009, and a fifth book, \"Rules for School\", in 2010.",
"title": ""
},
{
"docid": "23650428",
"text": "James \"Sydeian\" Brown who writes under the pen name \"James Richardson-Brown\", is a British author, best known as the creator of \"The Sydeian Coalition\" steampunk/science fiction series, books, 3-D artworks and RPG. The \"Sydeian\" series has garnered a cult following around the world with fans from the UK, America, South Africa, India, etc. He is also known for his promotion of steampunk in the UK and for coining the term \"Steamgoth\" a movement that is fast growing in popularity",
"title": ""
},
{
"docid": "28699293",
"text": "Mark Burgess (born 26 April 1957; pen name Simon Goswell for two books) is best known as an English author and illustrator of children's literature. He has illustrated books by Tony Bradman and Martin Waddell. Among his most recent assignments, he illustrated \"Return to the Hundred Acre Wood\", the authorized sequel of Winnie-the-Pooh.",
"title": ""
},
{
"docid": "33337403",
"text": "Jon Miller (born John Miller, 14 July 1921 – 30 July 2008) was a British television presenter who was best known for his appearances on the educational children's television science programme \"How\" between 1966 and 1981 with Jack Hargreaves, Bunty James and Fred Dinenage.",
"title": ""
},
{
"docid": "160121",
"text": "Fredric Wertham ( ; March 20, 1895 – November 18, 1981) was a German-educated American psychiatrist and crusading author who protested the purportedly harmful effects of violent imagery in mass media and comic books on the development of children. His best-known book was \"Seduction of the Innocent\" (1954), which suggested that comic books were dangerous to children. Wertham's criticisms of comic books helped spark a U.S. Congressional inquiry into the comic book industry and the creation of the Comics Code. He called television \"a school for violence\", and said \"If I should meet an unruly youngster in a dark alley, I prefer it to be one who has not seen \"Bonnie and Clyde\".\"",
"title": ""
},
{
"docid": "33327674",
"text": "Bunty James (born 1933, Maryport, Cumberland, England) is a former British television presenter who is best known for her appearances on the educational children's television science programme \"How\" in the 1960s and 1970s with Jack Hargreaves, Jon Miller and Fred Dinenage.",
"title": ""
},
{
"docid": "784771",
"text": "Thomas Michael Bond {'1': \", '2': \", '3': \", '4': \"} (13 January 1926 – 27 June 2017), who wrote under the pen name Michael Bond, was a British author. He is best known for a series of fictional stories for children, featuring the character of Paddington Bear. More than 35 million Paddington books have been sold around the world, and the characters have also been featured in film and on television. His first book was published in 1958 and his last in 2017, a span of 59 years.",
"title": ""
},
{
"docid": "20688463",
"text": "Roland Bruce Harvey (11 December 1945) is an Australian children's illustrator, and author. He is best known as an illustrator of children's books using pen, ink and watercolour.",
"title": ""
},
{
"docid": "23947777",
"text": "Etan Boritzer (born 1950) is an American writer of children’s literature who is best known for his book \"What is God?\" first published in 1989. His best selling \"What is?\" illustrated children's book series on character education and difficult subjects for children is a popular teaching guide for parents, teachers and child-life professionals.",
"title": ""
},
{
"docid": "5470991",
"text": "Walkabout is a novel written by James Vance Marshall, first published in 1959 as \"The Children\". It is about two children who get lost in the Australian Outback and are helped by an Aborigine on his walkabout. A film based on the book, with the same title came out in 1971, but deviated from the original plot.",
"title": ""
},
{
"docid": "31604493",
"text": "Robert Kinerk is an author who is best known for his children's books. Kinerk has written \"Clorinda\", \"Clorinda Takes Flight\", \"Bear's First Christmas\", and \"Oh, How Sylvester Can Pester!\". He is a Graduate of Santa Clara University and the University of Notre Dame. Before he became an author, he was a journalist and playwright.",
"title": ""
},
{
"docid": "2508679",
"text": "Peter James Gouldthorpe (born 30 July 1954) is an Australian artist and author best known for his children's books.",
"title": ""
},
{
"docid": "30738808",
"text": "William Matthew Scott (born Leeds 30 September 1893; d. Herne Bay 7 May 1964), pen name Will Scott, was a British author of stories and books for adults and children, published from 1920 to 1965. Towards the end of his life he was best known for \"The Cherrys\" series, written for children and published between 1952 and 1965. However, in earlier years he was known for his detective novels, his stage plays which were made into films, notably \"The Limping Man\" in 1931 and 1936, and for the 2,000 short stories that he contributed to magazines and newspapers; believed to be a record for the United Kingdom during his lifetime. As of 2011, his books are out of print.",
"title": ""
},
{
"docid": "35772719",
"text": "Ian's Walk: A Story about Autism is a book about autism by Laurie Lears, who also wrote \"Waiting for Mr. Goose\", a book about Attention deficit hyperactivity disorder. The story tells of a child with autism, and a walk with his sisters (who are frustrated with his stereotypical behaviour), and how they begin to understand him after he wanders off. \"Ian's Walk\" is regarded as a useful tool to help family members of children with autism understand associated behaviours.",
"title": ""
},
{
"docid": "2943859",
"text": "Ronald Welch (14 December 1909 – 5 February 1982) was the pen name of the Welsh writer Ronald Oliver Felton TD, writing in English. He took the name from his wartime service in the Welch Regiment. Welch is best known for children's historical fiction. He won the 1956 Carnegie Medal from the Library Association, recognising the year's best children's book by a British author, for \"Knight Crusader\", the first novel in the so-called Carey Family series.",
"title": ""
},
{
"docid": "1544138",
"text": "Philip William Turner (3 December 1925 – January 2006) was an English writer best known for his children's books set in the fictional town of Darnley Mills (1964–1977). Under the pen name Stephen Chance he is known for the Reverend Septimus Treloar mystery fiction series (1971–1979).",
"title": ""
},
{
"docid": "30723366",
"text": "Thomas Starling Sullivant (1854–1926) was an American cartoonist who signed his work T. S. Sullivant. His work appeared most frequently in the pages of the humorous \"Life\" magazine. Best known for his animal and ethnic caricatures, he also drew political cartoons and comic strip toppers, and illustrated children's books. He drew in a heavily cross-hatched pen-and-ink style, with humans and animals depicted with greatly exaggerated features that are nevertheless firmly rooted in his understanding of correct anatomy.",
"title": ""
},
{
"docid": "5197029",
"text": "Dan Greenburg (born June 20, 1936) is an American writer, humorist, and journalist. His more than 70 books have been published in 20 languages in 24 countries. His best-selling books for adults include \"How to Be a Jewish Mother\", \"How to Make Yourself Miserable\", \"Love Kills\", \"Exes\", and \"How to Avoid Love and Marriage\". He writes four series of children's books, \"The Zack Files\", \"Secrets of Dripping Fang\", \"Maximum Boy\", and \"Weird Planet\".",
"title": ""
},
{
"docid": "20884855",
"text": "Teddy Dressing is a picture book by Bethany M. Owens and David James Owens, published in 1986. It teaches independence through an illustrated story about a teddy bear getting dressed one morning, thus helping children identify clothing items and learn how to dress themselves.",
"title": ""
},
{
"docid": "12306159",
"text": "Reginald James MacGregor was a British author of children's literature who wrote numerous books and plays between the 1920s and 1950s, as RJ McGregor. His early books had Far Eastern settings. His most successful books were \"The Young Detectives\" and its sequels. These books charted the adventures of a family where the children had the same names as his children. He was the Headmaster of Bristol Grammar Preparatory School, and was a great influence on the many pupils who passed through the school, including Tunku Osman Tunku Mohammad Jewa.",
"title": ""
},
{
"docid": "33550042",
"text": "Timm Thaler oder Das verkaufte Lachen (roughly translated as Timm Thaler, or the Traded Laughter and best known as simply Timm Thaler) is a 1962 children's novel by German author James Krüss. Regarded by the \"Oxford Encyclopedia of Children's Literature\" as Krüss' best known children's book, \"Timm Thaler\" tells the story of a boy who trades his enchanting laughter to a wealthy mysterious Mephistopheles-like Baron in exchange for the ability to win any bet he makes. Regretting the exchange, he undertakes a four-year journey to win his laughter back. In 1979, Krüss wrote a sequel novel, Timm Thalers Puppen oder Die verkaufte Menschenliebe (roughly translated as Timm Thaler's Puppets, or the Traded Love for Mankind).",
"title": ""
}
] |
978
|
How does a tax exemption for an action = penalty for inaction?
|
[
{
"docid": "503034",
"text": "\"What it means is that you can always come up with alternative framings where the difference between two options is stated as a gain or a loss, but the effect is the same in either case. For instance, if I offer to sell a T-shirt for $10 and offer a cash discount of $1, you pay $10 if buying with a credit card or $9 if buying with cash. If I instead offer the shirt for $9 with a $1 surcharge for credit card use, you still pay $10 if buying with a credit card or $9 if buying with cash. The financial result is the same in either case, but psychologically people may perceive them differently and make different buying decisions. In a tax situation it may be more complicated since exemptions wouldn't directly reduce your tax, but only your taxable income. However, you can still see that, in general, having to pay $X more in tax for not doing some action (e.g., not purchasing health insurance) is the same as being able to pay $X less in tax as a reward for doing the action. Either way, doing the action results in you paying $X less than you would if you didn't do it; the only difference is in which behavior (doing it or not doing it) is framed as the \"\"default\"\" option. Again, these framings may differentially influence people's behavior even when the net result is the same.\"",
"title": ""
},
{
"docid": "122908",
"text": "\"There's a significant difference between \"\"discount\"\" and \"\"surcharge\"\". For starters - legal difference. If you have a list price of $X - that's the price you're committed to sell regardless of the payment method. So it doesn't matter if I pay with cash or credit - I'll pay $X. However, it costs you more when I pay with credit - so you want to pass that cost on me. You charge me surcharge - an addition to the price. In some States in the US and in some other countries - that is against the law. You cannot add on top of the listed price any amount regardless of the payment method. However, you can say that the list price is $X, which includes the assumed credit card surcharge of $Y. And then you give discount of $Y to anyone not paying with credit card. The list price is still $X, regardless of the payment method. You don't have to give the discount, the discount is your cost of doing business. But that would be legal in some places (not all!) that forbid credit card surcharge. So the main difference from legal perspective is that you're not allowed to add to the list price, but you're allowed to discount from it. Regarding taxes - exemption/deduction is not a penalty for negative. Exemption/deduction is an implementation of a social policy. For example, it is for the public benefit for everyone to own a house. So the Congress comes up with a deduction of mortgage interest. However, you're not penalized if you don't own a house by paying higher taxes. Your tax rate doesn't change. You just don't get to deduct something that you might be able to deduct had you owned a house with a mortgage. This is, again - a discount of a list price, not a surcharge. You're not penalized if you don't have a house or don't have a mortgage, but if you do - you get a break. The author you're quoting claims that bottom line would be the same as if you considered the absence of a deduction as a penalty. But that's not true, because even if you do have a mortgage you may not be able to deduct it because your income is too high, the mortgage is for too much, or your mortgage is not on the primary residence. So mere existence of the mortgage doesn't directly correlate to the existence of the deduction. Similarly with credit card surcharges - you may get a cash discount, but you may get the similar amount of money back even if you use a credit card. Not as a cash discount but rather as rewards, cash-backs or points. However, if there's no cash discount, you won't be getting these if you're paying cash. So again - you're not penalized for having a credit card by not getting a discount, because you may still get it in a different way - and if you don't, you still may end up not getting it. So the quote is a rather simplistic and negative view and more of an opinion than stating a fact.\"",
"title": ""
}
] |
[
{
"docid": "15319",
"text": "\"3) NOT to claim her as my dependent. No additional tax return (since she is NOT my dependent), but also no penalty. My end of year balance would be $0 No. Not claiming her as a dependent does not save you from being responsible for her penalty. You are responsible for her penalty if she is your dependent (i.e. she meets the conditions for being your dependent), regardless of whether you claim her on your tax return or not. If you have the option of claiming her or not, then she is your dependent, and you are responsible for her penalty. 26 CFR 1.5000A-1(c)(2)(i): For a month when a nonexempt individual does not have minimum essential coverage, if the nonexempt individual is a dependent (as defined in section 152) of another individual for the other individual's taxable year including that month, the other individual is liable for the shared responsibility payment attributable to the dependent's lack of coverage. An individual is a dependent of a taxpayer for a taxable year if the individual satisfies the definition of dependent under section 152, regardless of whether the taxpayer claims the individual as a dependent on a Federal income tax return for the taxable year. [...] Form 1040 instructions, Line 61: [...] If you had qualifying health care coverage (called minimum essential coverage) for every month of 2015 for yourself, your spouse (if filing jointly), and anyone you can or do claim as a dependent, check the box on this line and leave the entry space blank. Otherwise, do not check the box on this line. If you, your spouse (if filing jointly), or someone you can or do claim as a dependent didn’t have coverage for each month of 2015 you must either claim a coverage exemption on Form 8965 or report a shared responsibility payment on line 61. [...] So you cannot check the box and must report exemptions for your sister, or report a shared responsibility payment. Form 8965 instructions, Definitions, \"\"Tax household\"\": For purposes of Form 8965, your tax household generally includes you, your spouse (if filing a joint return), and any individual you claim as a dependent on your tax return. It also generally includes each individual you can, but don't, claim as a dependent on your tax return. [...] Your sister is part of your tax household regardless of whether you claim her, and you must compute her shared responsibility payment for any months she did not have insurance and did not qualify for an exemption.\"",
"title": ""
},
{
"docid": "261003",
"text": "ADP does not know your full tax situation and while the standard exemption system (actually designed by the IRS not ADP) works fairly well for most people it is an approximation. This system is designed so most people will end up with a small refund while some people will end up owing small amounts. So, while it is possible that ADP has messed up the calculations it is unlikely this is the cause. The most likely cause is that approximation ends ups making you pay less tax during the year than you actually owe. A few people like your friend may end up owing large amounts due to various circumstances. It is always your responsibility to make sure you pay enough tax throughout the year. While this technically means that you need to do your taxes every quarter during the year to make sure you pay the correct tax during the year, for most people this ends up being unnecessary as the approximation works fine. It is possible the exemption system failed your friend, but much more commonly people owe penalties because they put the wrong number of exemptions or had other side income. On a related note, most people in finance would argue that your situation where you owe some money at tax time, but not so much that you have to pay a penalty, is actually the best way to go. Getting a tax refund actually means you paid more tax than you needed to. This is similar to giving an interest-free loan to the government.",
"title": ""
},
{
"docid": "97852",
"text": "Legally, do I have anything to worry about from having an incorrectly filed W-4? What you did wasn't criminal. When you submitted the form it was correct. Unfortunately as your situation changed you didn't adjust the form, that mistake does have consequences. Is there anything within my rights I can do to get the company to take responsibility for their role in this situation, or is it basically my fault? It is basically your fault. The company needs a w-4 for each employee. They will use that W-4 for every paycheck until the government changes the regulation, or your employment ends, or you submit a new form. Topic 753 - Form W-4 – Employee's Withholding Allowance Certificate If an employee qualifies, he or she can also use Form W-4 (PDF) to tell you not to deduct any federal income tax from his or her wages. To qualify for this exempt status, the employee must have had no tax liability for the previous year and must expect to have no tax liability for the current year. However, if the employee can be claimed as a dependent on a parent's or another person's tax return, additional limitations may apply; refer to the instructions for Form W-4. A Form W-4 claiming exemption from withholding is valid for only the calendar year in which it is filed with the employer. To continue to be exempt from withholding in the next year, an employee must give you a new Form W-4 claiming exempt status by February 15 of that year. If the employee does not give you a new Form W-4, withhold tax as if he or she is single, with no withholding allowances. However, if you have an earlier Form W-4 (not claiming exempt status) for this employee that is valid, withhold as you did before. (I highlighted the key part) Because you were claiming exempt they should have required you to update that form each year. In your case that may not have applied because of the timing of the events. When do you submit a new form? Anytime your situation changes. Sometimes the change is done to adjust withholding to modify the amount of a refund. Other times failure to update the form can lead to bigger complication: when your marital status changes, or the number of dependents changes. In these situations you could have a significant amount of under-withheld, which could lead to a fine later on. As a side note this is even more true for the state version of a W-4. Having a whole years worth of income tax withholding done for the wrong state will at a minimum require you to file in multiple states, it could also result in a big surprise if the forgotten state has higher tax rate. Will my (now former) employee be responsible for paying their portion of the taxes that were not withheld during the 9 months I was full-time, tax Exempt? For federal and state income taxes they are just a conduit. They take the money from your paycheck, and periodically send it to the IRS and the state capital. Unless you could show that the pay stubs said taxes were being withheld, but the w-2 said otherwise; they have no role in judging the appropriateness of your W-4 with one exception. Finally, and I am not too hopeful on this one, but is there anything I can do to ease this tax burden? I understand that the IRS is owed no matter what. You have one way it might workout. For many taxpayers who have a large increase in pay from one year to the next, they can take advantage of a safe-harbor in the tax law. If they had withheld as much money in 2015 as they paid in 2014, they have reached the safe-harbor. They avoid the penalty for under withholding. Note that 2014 number is not what you paid on tax day or what was refunded, but all your income taxes for the entire year. Because in your case your taxes for the year 2014 were ZERO, that might mean that you automatically reach the safe-harbor for 2015. That makes sense because one of the key requirements of claiming exempt is that you had no liability the year before. It won't save you from paying what you owe but it can help avoid a penalty. Lessons",
"title": ""
},
{
"docid": "12940",
"text": "This is a frequent problem for anyone with a large amount of deductions, whether it is student loan interest, home mortgage interest, charitable contributions, or anything else. As an employee getting your tax withheld from your check, your options to reduce the amount withheld are limited. The HR department has no control over how much they withhold; the amount is calculated using a standard formula based on the number of exemptions you tell them. The number of exemptions you claim on your W-4 form does not have to match reality. If you currently have 1 exemption claimed, ask them what the withholding would be if you claimed 4 exemptions. If that's not enough, go higher. As long as you are not withholding so little that you have a large tax bill at the end of the year, you are fine. Of course, when you do your taxes, you need to have the correct number of exemptions claimed on your 1040, but this number does not need to match your W-4.",
"title": ""
},
{
"docid": "1705",
"text": "\"Yes, your tax bracket is 25%. However, that doesn't mean that your take home pay will be 75% of your salary. There is much more that goes into figuring out what your take home pay will be. First, you have payroll taxes. This is often listed on your pay stub as \"\"FICA.\"\" The Social Security portion of this tax is 6.2% on the first $118,500 of your pay and the Medicare portion is another 1.45% on the first $200,000. (Your employer also has to pay additional tax that does not appear on your stub.) So 7.65% of your salary gets removed off the top. In addition to the federal income taxes that get withheld, you may also have state income taxes that get withheld. The amount varies with each state. Also, the 25% tax bracket does not mean that your tax is 25% of your entire salary. You step through the tax brackets as your income goes up. So part of your salary is taxed at 10%, part at 15%, and the remainder is at 25%. The amount of federal income tax that is withheld from your paycheck is really a rough estimate of how much tax you actually owe. There are lots of things that can reduce your tax liability (personal exemptions, deductions, credits) or increase your tax (investment income, penalties). When you do your tax return, you calculate the actual tax that you owe, and you either get a refund if too much was taken out of your check, or you need to send more money in if too little was taken out.\"",
"title": ""
},
{
"docid": "555404",
"text": "401(k) withdrawals - early or otherwise - are not subject to FICA or Medicare taxes. That's because they already were taxed when they were contributed. (And of course, the earnings from the 401(k) contributions are not earned income and thus are not subject to payroll taxes for that reason.) While 401(k) contributions are exempt from federal (and generally state) income taxes, they aren't exempt from payroll taxes - and as such, you'll see two separate amounts on your W2 and paystub if you contributed: the amount that is subject to those taxes, and the amount that is subject to income tax. So, no, you don't have to pay payroll (FICA, Social Security) taxes on your early withdrawal. As for the penalty, that is basically an extra tax - so if you withdraw $1000, you pay income tax at your marginal rate plus 10% penalty; if your marginal rate is 25% [and you're not moving across a rate step boundary], you will pay 25%*(1000) + 10%*(1000).",
"title": ""
},
{
"docid": "416240",
"text": "Look into the Coverdell Education Savings Account (ESA). This is like a Roth IRA for higher education expenses. Withdrawals are tax free when used for qualified expenses. Contributions are capped at $2000/year per beneficiary (not per account) so it works well for young kids, and not so well for kids about to go to College. This program (like all tax law) are prone to changes due to action (or inaction) in the US Congress. Currently, some of the benefits are set to sunset in 2010 though they are expected to be renewed in some form by Congress this year.",
"title": ""
},
{
"docid": "584238",
"text": "\"the state of New Mexico provides guidance in this exact situation. On page 4: Gross receipts DOES NOT include: Example: When the seller passes tax to the buyer, the seller should separate, or “back out”, that tax from the total income to arrive at \"\"Gross Receipts,\"\" the amount reported in Column D of the CRS-1 Form. (Please see the example on page 48.) and on page 48: How do I separate (“back out”) gross receipts tax from total gross receipts? See the following examples of how to separate the gross receipts tax: 1) To separate (back out) tax from total receipts at the end of the report period, first subtract deductible and exempt receipts, and then divide total receipts including the tax for the report period by one plus the applicable gross receipts tax rate. For example, if your tax rate is 5.5% and your total receipts including tax are $1,055.00 with no deductions or exemptions, divide $1,055.00 by 1.055. The result is your gross receipts excluding tax (to enter in Column D of the CRS-1 Form) or $1,000. 2) If your tax rate is 5.5%, and your total gross receipts including tax are $1,055.00, and included in that figure are $60 in deductions and another $45 in exemptions: a) Subtract $105 (the sum of your deductions and exemptions) from $1,055. The remainder is $950. This figure still includes the tax you have recovered from your buyers. b) Divide $950 by 1.055 (1 plus the 5.5% tax rate). The result is $900.47. c) In Column D enter the sum of $900.47 plus $60 (the amount of deductible receipts)*, or $960.47. This figure is your gross receipts excluding tax.\"",
"title": ""
},
{
"docid": "65698",
"text": "The purpose of the W-4 form is to allow you to adjust the withholding to meet your tax obligations. If you have outside non-wage income (money from tutoring) you will have to fill out the W-4 to have extra taxes withheld. If you have deductions (kids, mortgages, student loan interest) then you need to adjust the form to have less tax taken out. Now if yo go so far that you owe too much in April, then you can get hit with penalties and a requirement to file your taxes quarterly the next year. Most years I adjust my W-4 to reflect changes to my situation. The idea is to use it to manage your withholding so that you minimize your refund without triggering the penalties. The HR department has advised you well. How to adjust: If you want to decrease withholding (making the refund smaller) add one to the number on the worksheet. In 2014 a change by 1 exemption is equal to a salary adjustment of $3,950. If this was spread over 26 paychecks that would be the same as lowering your salary by ~$152. If you are in the 15% tax bracket that increases your take home pay by ~10 a check.",
"title": ""
},
{
"docid": "442146",
"text": "Yes, you can send in a 2012 1040-ES form with a check to cover your tax liability. However, you will likely have to pay penalties for not paying tax in timely fashion as well as interest on the late payment. You can have the IRS figure the penalty and bill you for it, or you can complete Form 2210 (on which these matters are figured out) yourself and file it with your Form 1040. The long version of Form 2210 often results in the smallest extra amount due but is considerably more time-consuming to complete correctly. Alternatively, if you or your wife have one or more paychecks coming before the end of 2012, it might be possible to file a new W-4 form with the HR Department with a request to withhold additional amounts as Federal income tax. I say might because if the last paycheck of the year will be issued in just a few days' time, it might already have been sent for processing, and HR might tell you it is too late. But, depending on the take-home pay, it might be possible to have the entire $2000 withheld as additional income tax instead of sending in a 1040-ES. The advantage of doing it through withholding is that you are allowed to treat the entire withholding for 2012 as satisfying the timely filing requirements. So, no penalty for late payment even though you had a much bigger chunk withheld in December, and no interest due either. If you do use this approach, remember that Form W-4 applies until it is replaced with another, and so HR will continue to withhold the extra amount on your January paychecks as well. So, file a new W-4 in January to get back to normal withholding. (Fix the extra exemption too so the problem does not recur in 2013).",
"title": ""
},
{
"docid": "480282",
"text": "You are correct that W-4s are very confusing for multiple income homes, and even more so if you change salary significantly during the year. There are just too many variables in those situations to provide an effective, simple form. Unfortunately, the best way to get accurate withholdings is trial-and-error. Try and estimate how much tax you'll have to pay for the year. There are several calculators out there, but essentially you can take your gross income, subtract the standard exemptions for you and all dependents, subtract the standard deductions (or estimate your itemized deductions), and compute your tax based on the federal tax tables. Then subtract any tax credits you may be eligible for. Then estimate your withholdings for the year by multiplying your current withholdings by the number of pay periods left, and adding your YTD withholdings. If your total withholdings are higher than your estimated tax, add one or two exemptions to reduce your withholdings (and vice versa). If all that sounds like a lot of work (which it is), at a minimum make sure you withhold as much tax as you paid last year. That way you avoid any tax penalties, but might have a tax bill when you file. If you want to be conservative and withhold a little extra that's fine - you might even end up with a refund when you file. The good news is it doesn't have to be exact; any difference will determine what you pay (or what refund you get) when you file.",
"title": ""
},
{
"docid": "505553",
"text": "While the US tax code does not directly impose an obligation to pay estimated taxes, it does impose a penalty on individuals for failure to pay enough taxes either through withholding or estimated tax. USMTG Anyone can choose how s/he wants to pay their taxes but they better deal with any consequences of not paying them instead of just complaining about it like most people do. Most people get the hatred towards the IRS but most complaints are misdirected and should be directed towards Congress who creates and messes around with the US Tax Code. Some people actually do not make estimated payments and pay any possible taxes with their returns knowing that there may be underpayment penalty. For those people, the penalty is relatively small compared to what they can do with the cash over a year's time (i.e. investing or paying down debt). It's their choice!",
"title": ""
},
{
"docid": "454951",
"text": "\"Does the money lending between us need to be reported in our tax reports? No. Will he be taxed more because of lending the money to me? Yes. Will I be taxed more because of borrowing the money from him? No. How shall we report it so as to minimize our taxes? You cannot. What is reported on your tax returns is the income. A loan is not an income, so nothing gets reported. However, when you repay the loan, assuming it has interest, the lender has income: the interest. Interest income is reported on schedule B of the regular (1040/1040A) tax return (or, in the case of non-resident for tax purposes, on line 9 of 1040NR). It is taxed as ordinary income, and since you're both foreigners - the lender should look into the treaty provisions that might be relevant. Generally it is not exempt from taxable income based on treaty exemptions for students (which is only for earned income), but there might be other rules in the treaty regarding interest income. If there's no (fair market or higher) interest, then there's \"\"assumed\"\" interest at the IRS mandated rates, which is considered a gift. If it amounts to more than the yearly gift exemption, the lender may be liable for gift tax (depending on the lender's and your status, and again - see treaties). \"\"Loan\"\" without an obligation to repay and without actual repaying will also be considered a gift for tax purposes. If the lender has no intentions of having the loan repaid (i.e.: making a gift), it will be better to pay your tuition bills instead of actually giving you the money: tuition is exempt from gift tax. Talk to a CPA/EA licensed in your state for a proper tax advice on this issue.\"",
"title": ""
},
{
"docid": "261189",
"text": "IANAL but I'd think common sense would say that if you take advantage of one of the special cases that allow you to withdraw from a retirement plan without penalty, and then for whatever reason you don't use the money for a legal purpose, you would have to either return the money or pay the tax penalty. And I'll go out on a limb here without any documentation and guess that if you lie to the IRS and say that you withdrew the money for an exempt purpose and instead use it to go on vacation and you get caught, that you will not only have to pay the tax penalty but will also be liable for criminal charges of tax fraud. If the law and/or IRS regulations say that the only legal exceptions are A, B, and C, that pretty clearly means that if you do D, you are breaking the law. And in the eyes of the government, failing to pay the taxes you owe is way worse than robbery, murder, or rape.",
"title": ""
},
{
"docid": "103842",
"text": "Does the 5 year rule apply on the After-tax 401k -> Roth 401k -> Roth IRA conversion of the 20000 (including 10000 earnings that was originally pre-tax)? No. The after-tax amounts are not subject to the 5 years rule. The earnings are. How does this affect Roth IRA withdrawal ordering rules with respect to the taxable portion of a single conversion being withdrawn before the non-taxable portion? Taxable portion first until exhausted. To better understand how it works, you need to understand the rationale behind the 5-year rule. Consider you have $100K in your IRA (traditional) and you want to take it out. Just withdrawing it would trigger a 10K statutory penalty, on top of the taxes due. But, you can use the backdoor Roth IRA, right? So convert the 100K, and then it becomes after-tax contribution to Roth IRA, and can be withdrawn with no penalty. One form filled ad 10K saved. To block this loophole, here comes the 5 years rule: you cannot withdraw after-tax amounts for at least 5 years without penalty, if the source was taxable conversion. Thus, in order to avoid the 10K penalty in the above situation, you have a 5-year cooling period, which makes the loophole useless for most cases. However amounts that are after tax can be withdrawn without penalty already, even from the traditional IRA, so there's no need in the 5 years cooling period. The withdrawal attribution is in this order: Roth IRA rollovers are sourced to the origin. E.g.: if you converted $100 to the Roth IRA at firm X and then a year later rolled it over to firm Y - it doesn't affect anything and the clock is ticking from the original date of the conversion at firm X. 5-year period applies to each conversion/rollover from a qualified retirement plan (see here). Distributions are applied to the conversions in FIFO order, so in one distribution, depending on the amounts, you may hit several different incoming conversions. The 5 years should be check on each of them, and the penalty applied on the amounts attributable to those that don't have enough time. 5-year period for contributions applies starting from the beginning of the first year of the first contribution that established your Roth IRA plan. The penalty applies to the amounts that were included in your gross income when conversion occurred, i.e.: doesn't apply on the amounts converted from after-tax sources. Note the difference from the traditional IRA - distributions from pre-tax sources are prorated between the non-deductible (basis) amounts and the deductible/earnings amounts (taxable). That is why the taxable amounts are first in the ordering of the distributions.",
"title": ""
},
{
"docid": "313012",
"text": "\"You are not the only one with this problem. When Intuit changed their pricing and services structure in 2015 a lot of people got angry, facing larger fees and having to go through an annoying upgrade just to get the same functionality (such as Schedule D, capital gains). You have several options: (1) Forget Turbo Tax and just use paper forms. That is what I do. Paper is reliable. (2) Use forms mode in Turbo Tax. Of course, that may be even more complicated than simply filing out paper forms. (3) Use a different service. If your income is below $64,000 the IRS has a free electronic filing service. Other online vendors have full taxes services for less than Turbo Tax. (4) Add the amount to ordinary income. Technically, as long as you report the income, you cannot be penalized, so if you add the capital gain to your ordinary income, then you have paid taxes on the income. Even if they send you a letter, you can send an answer that you added it to ordinary income and that will satisfy them. Of course you pay a higher rate on your $26 if you do that. (5) If you are in the 15% or below income bracket you are exempt from capital gains, and you can omit it. Don't believe the nervous Nellies who say the IRS will burn your house down if you don't report $26 in capital gains. Penalties are assessed on the percentage of TAXES you did not pay (0.5% penalty per month). Since 0.5% of $0 is $0 your penalty is $0. The IRS knows this. The IRS does not send out assessment letters for $0. (6) Even if you are above the 15% bracket, there is likelihood it is still a no-tax situation (see 5 above). (7) Worst case scenario: you are making a million dollars per year and you omit your $26 capital gains from your return. The IRS will send you an assessment letter for about $10. You can then send them a separate check or money order to pay it. In all honesty I have omitted documented tax items, like taxable interest, that the IRS knows about many times and never gotten an assessment letter. Once I made a serious math error on my return and they sent me an assessment letter, which I just paid, end of story. And that was for a lot more than $26. The technical verbiage for something like this in IRS lingo is CP-2000, underreported income. As you can see from this official IRS web page, basically what they do is guess how much they think you owe and send you a bill. Then you pay it. If you do so in time, you don't even get a 0.5% interest penalty on your $6.75 owed or whatever it is. (8) Go hog wild. As long as you are risking an assessment on your $26, why not go hog wild and just let the IRS compute all your taxes for you? Make a copy of your income statements, then mail them to the IRS with a letter that says, \"\"Hi, I am Mr. Odinson, my SSN is XXX-XX-XXXX. My address is XYZ. I am unable to compute my taxes due to a confused state of mind. I am hereby requesting a tax assessment for the 2016 tax year.\"\" Make sure you sign and date the letter. In all probability they will compute the full assessment and send you a bill (or refund).\"",
"title": ""
},
{
"docid": "517723",
"text": "Roth IRAs divide your withdrawal into 3 categories: Contributions, Conversions, and Earnings. This is significant, because each have different tax consequences and the order of withdrawal is dictated by tax law. You can withdraw your contributions in less than 5 years for any reason (home buyer or not). You cannot withdraw your conversions or earnings without waiting 5 years unless you pay the 10% penalty. The home buyer exemption is only after the 5 years are met. Further detail found on the motley fool: home purchase exemption, distributions, early withdrawals.",
"title": ""
},
{
"docid": "502150",
"text": "\"The biggest and primary question is how much money you want to live on within retirement. The lower this is, the more options you have available. You will find that while initially complex, it doesn't take much planning to take complete advantage of the tax system if you are intending to retire early. Are there any other investment accounts that are geared towards retirement or long term investing and have some perk associated with them (tax deferred, tax exempt) but do not have an age restriction when money can be withdrawn? I'm going to answer this with some potential alternatives. The US tax system currently is great for people wanting to early retire. If you can save significant money you can optimize your taxes so much over your lifetime! If you retire early and have money invested in a Roth IRA or a traditional 401k, that money can't be touched without penalty until you're 55/59. (Let's ignore Roth contributions that can technically be withdrawn) Ok, the 401k myth. The \"\"I'm hosed if I put money into it since it's stuck\"\" perspective isn't true for a variety of reasons. If you retire early you get a long amount of time to take advantage of retirement accounts. One way is to primarily contribute to pretax 401k during working years. After retiring, begin converting this at a very low tax rate. You can convert money in a traditional IRA whenever you want to be Roth. You just pay your marginal tax rate which.... for an early retiree might be 0%. Then after 5 years - you now have a chunk of principle that has become Roth principle - and can be withdrawn whenever. Let's imagine you retire at 40 with 100k in your 401k (pretax). For 5 years, you convert $20k (assuming married). Because we get $20k between exemptions/deduction it means you pay $0 taxes every year while converting $20k of your pretax IRA to Roth. Or if you have kids, even more. After 5 years you now can withdraw that 20k/year 100% tax free since it has become principle. This is only a good idea when you are retired early because you are able to fill up all your \"\"free\"\" income for tax conversions. When you are working you would be paying your marginal rate. But your marginal rate in retirement is... 0%. Related thread on a forum you might enjoy. This is sometimes called a Roth pipeline. Basically: assuming you have no income while retired early you can fairly simply convert traditional IRA money into Roth principle. This is then accessible to you well before the 55/59 age but you get the full benefit of the pretax money. But let's pretend you don't want to do that. You need the money (and tax benefit!) now! How beneficial is it to do traditional 401ks? Imagine you live in a state/city where you are paying 25% marginal tax rate. If your expected marginal rate in your early retirement is 10-15% you are still better off putting money into your 401k and just paying the 10% penalty on an early withdrawal. In many cases, for high earners, this can actually still be a tax benefit overall. The point is this: just because you have to \"\"work\"\" to get money out of a 401k early does NOT mean you lose the tax benefits of it. In fact, current tax code really does let an early retiree have their cake and eat it too when it comes to the Roth/traditional 401k/IRA question. Are you limited to a generic taxable brokerage account? Currently, a huge perk for those with small incomes is that long term capital gains are taxed based on your current federal tax bracket. If your federal marginal rate is 15% or less you will pay nothing for long term capital gains, until this income pushes you into the 25% federal bracket. This might change, but right now means you can capture many capital gains without paying taxes on them. This is huge for early retirees who can manipulate income. You can have significant \"\"income\"\" and not pay taxes on it. You can also stack this with before mentioned Roth conversions. Convert traditional IRA money until you would begin owing any federal taxes, then capture long term capital gains until you would pay tax on those. Combined this can represent a huge amount of money per year. So littleadv mentioned HSAs but.. for an early retiree they can be ridiculously good. What this means is you can invest the maximum into your HSA for 10 years, let it grow 100% tax free, and save all your medical receipts/etc. Then in 10 years start withdrawing that money. While it sucks healthcare costs so much in America, you might as well take advantage of the tax opportunities to make it suck slightly less. There are many online communities dedicated to learning and optimizing their lives in order to achieve early retirement. The question you are asking can be answered superficially in the above, but for a comprehensive plan you might want other resources. Some you might enjoy:\"",
"title": ""
},
{
"docid": "351925",
"text": "\"1 - in most cases, the difference between filing joint or married filing single is close to zero. When there is a difference you're better off filing joint. 2 - The way the W4 works is based on how many allowances you claim. Unfortunately, even in the day of computers, it does not allow for a simple \"\"well my deduction are $xxx, don't tax that money.\"\" Each allowance is equal to one exemption, same as you get for being you, same as the wife gets, same as each kid. 3 people X $3800 = $11,400 you are telling the employer to take off the top before calculating your tax. She does this by using Circular E and is able to calculate your tax as you request. If one is in the 15% bracket, one more exemption changes the tax withheld by $570. So if you were going to owe $400 in April, one few exemption will have you overpay $170. i.e. in this 15% bracket, each exemption changes annual withholding by that $570. For most people, running the W4 numbers will get them very close, and only if they are getting back or owing over $500, will they even think of adjusting. 3 - My recently published Last Minute Tax Moves offers a number of interesting ideas to address this. The concept of grouping deductions in odd years is worth noting. 4 - I'm not sure what this means, 2 accounts each worth $5000 should grow at the same rate if invested the same. The time it makes sense to load one person's account first is if they have better matching. You say you are not sure what percent your wife's company matches. You need to change this. For both of your retirement plans you need to know every detail, exact way to maximize matching, expense ratios for the investments you choose, any other fees, etc. Knowledge is power, and all that. In What is an appropriate level of 401k fees or expenses in a typical plan? I go on to preach about how fees can wipe out any tax benefit over time. For any new investor, my first warning is always to understand what you are getting into. If you can't explain it to a friend, you shouldn't be in it. Edit - you first need to understand what choices are within the accounts. The 4% and 6% are in hindsight, right? These are not fixed returns. You should look at the choices and more heavily fund the account with the better selection. Deposit to her account at least to grab the match. As far as the longer term goals, see how the house purchase goes. Life has a way of sending you two kids and forcing you to tighten the budget. You may have other ideas in three years. (I have no P2P lending experience, by the way.) Last - many advise that separate finances are a bad path for a couple. It depends. Jane and I have separate check books, and every paycheck just keep enough to write small checks without worry, most of the money goes to the house account. Whatever works for you is what you should do. We've been happily married for most of the 17 years we've been married.\"",
"title": ""
},
{
"docid": "334107",
"text": "\"This kind of investment is called \"\"sweat equity\"\". It is sometimes taken into account by lenders and other investors. Such investors look at the alleged value of the input labor with a very skeptical eye, but they often appreciate that the entrepreneur has \"\"skin in the game\"\". The sort of analysis described by the original poster is useful for estimating \"\"economic profit\"\" -- how much better off was the entrepreneur than if he had done something else with his time. But this sort of analysis is not applicable for tax purposes for most small businesses in the United States. It is usually not in the entrepreneur's interest to use this method of accounting for tax purposes, for three reasons: It requires setting up the business in such a way that it can pay him wages or salaries for his time. The business might not have enough cash resources to do so. Furthermore, setting up the business in this way requires legal and accounting expertise, which is expensive. If the entrepreneur does set up the business like this, the wages and salaries will be subject to tax. Wage and salary tax rates are often much higher than capital gains tax rates, especially when one considers taxes like Social Security taxes, Medicare taxes, and Business & Occupation taxes. If the entrepreneur does set up the business like this, the taxes on the wages and salaries would be due long before the hoped-for sale of the company. The sale of the company might never happen. This results in a time-value-of-money penalty, an optionality penalty, and a risk penalty.\"",
"title": ""
},
{
"docid": "278902",
"text": "The advice is always to not get a big refund from the IRS, because that is giving them an interest free loan. You actually have an opportunity to get an interest free loan from them. When you file your taxes for 2013 note how much you paid in taxes. Not the check you had to send in with your tax form or the refund you received, but the total amount in taxes you paid. Multiply that amount by 1.1 or (110%). For example $8,000 * 1.10 = $8,800. When you get your paychecks in 2014 you goal is to make sure that your federal taxes (not state, Social security or medicare) taken from your paycheck will get you over that number $8,800 /26 or ~350 a paycheck. Keep in mind that the later you start the more each check needs to be. You will owe them a big check in April 2015. But because of the 110% rule you will not owe interest, penalties, or have to deal with quarterly taxes. The 110% rule exempts you from these if you end them 110% as much a you paid in taxes the previous year. Note that no matter how you pay your taxes for 2014: big check now, extra per paycheck, or minimum now; you will have to watch your withholding during 2015 because the 110% rule won't protect you.",
"title": ""
},
{
"docid": "300367",
"text": "Tax-exempt interest (and dividends attributable to tax-exempt interest) is required to be reported on Form 1040 line 8b (or the analogous line of Form 1040A). While it is not directly taxed, it does come into play in the calculation of taxable income and various credits. For example, tax-exempt interest is counted when determining the portion of Social Security benefits to be included in gross income.",
"title": ""
},
{
"docid": "444899",
"text": "With a $40,000 payment there is a 100% chance that the owner will be claiming this as a business expense on their taxes. The IRS and the state will definitely know about it, and the risk of interest and penalties if it is not claimed as income make the best course of action to see a tax adviser. Because taxes will not be taken out by the property owner, the tax payer should also make sure that the estimated $10,000 in federal taxes, if they are in the 25% tax bracket, doesn't trigger other tax issues that could result in penalties, or the need to file quarterly taxes next year. This kind of extra income could also result in a change or an elimination of a health care subsidy. A unexpected mid-year change could trigger the need to refund the subsidy received this year via the tax form next April.",
"title": ""
},
{
"docid": "55901",
"text": "Am I eligible for the tax exemption if yes then under which section. Generally Personal loans are not eligible for tax exemption. Only housing loans from qualified institutions are eligible for tax deduction. As per the income tax act; The house should be in your name. The home loans taken from recognised institutions are fully qualified under section 24B and 80C. This means you can claim Interest exemption under 24B and Principal repayment under 80C. The Act also specifies that loan can be taken from friends/relatives for construction of property and will be eligible for Interest exemption under 24B only. The principal will not be eligible for exemption under 80C. Read the FAQ from Income Tax India. There has to be certificate showing how much interest was paid on the said loan. Further there should be records/receipts on how the money was spent. There is difference of opinion amongst CA. It is best you take a professional advise.",
"title": ""
},
{
"docid": "338170",
"text": "My understanding (I've never filed one myself) is that the 1040ES is intended to allow you to file quarterly and report unpredictable income, and to pay estimated taxes on that income. I was in the same sort of boat for 2016 -- I had a big unexpected income source in 2015, and this took away my Safe Harbor for 2016. I adjusted my w-2 to zero exemptions (eventually) and will be getting a refund of about 1% of our income. So lets say you make 10000 in STG in March, and another 15000 in STG in April. File a quarterly 1040-ES between March 31 and April 15. Report the income, and pay some tax. You should be able to calculate the STCG Tax for 10k pretty easily. Just assume that it comes off the top and doesn't add at all to your deductions. Then for April, do the same by June 15. Just like your W-2 is used to estimate how much your employer should withhold, the 1040ES is designed to estimate how much extra you need to pay to the IRS to avoid penalties. It'll all get resolved after you file your final 1040 for the 2017 calendar year.",
"title": ""
},
{
"docid": "83769",
"text": "\"I think there are several issues here. First, there's the contribution. As littleadv said, there is no excess contribution. Excess contribution is only if you exceed the contribution limit. The contribution limit for Traditional IRAs does not depend on how high your income goes or whether you have a 401(k). It's the deduction limit that may depend on those things. Not deducting it is perfectly legitimate, and is completely different than an \"\"excess contribution\"\", which has a penalty. Second, the withdrawal. You are allowed to withdraw contributions made during a year, plus any earnings from those contributions, before the tax filing deadline for the taxes of that year (which is April 15 of the following year, or even up to October 15 of the following year), and it will be treated as if the contribution never happened. No penalties. The earnings will be taxed as regular income (as if you put it in a bank account). That sounds like what you did. So the withdrawal was not an \"\"early withdrawal\"\", and the 1099-R should reflect that (what distribution code did they put?). Third, even if (and it does not sound like the case, but if) it doesn't qualify as a return of contributions before the tax due date as described above (maybe you withdrew it after October 15 of the following year), as littleadv mentioned, your contribution was a non-deductible contribution, and when withdrawing it, only the earnings portion (which after such a short time should only be a very small part of the distribution) would be subject to tax and penalty.\"",
"title": ""
},
{
"docid": "58683",
"text": "From Schwab With a Roth, withdrawals of contributions are always tax-free because you've already paid income taxes on that money. So are withdrawals of earnings of up to $10,000 under the homebuyer exemption, assuming you've had the Roth for five-plus years. But if you withdraw more than $10,000 in earnings, that money will be subject to both ordinary income taxes and the 10 percent penalty.",
"title": ""
},
{
"docid": "254514",
"text": "Your phrasing of the question isn't very clear, but I believe you're asking: Does our total household income classify us as tax exempt? Or, can we avoid filing taxes if we make $22,500 or less per year? The answer is no. Your tax liability will be very low, and if you have dependents or other deductible expenses (mortgage interest, 401K contributions, etc.), you're likely looking at a close to $0 liability. You still have to file your taxes, and you can't claim exempt on your W-4. Even if you did qualify to be tax exempt, you still have to file taxes.",
"title": ""
},
{
"docid": "411606",
"text": "\"A loan is not a taxable income. Neither is a gift. Loans are repaid with interest. The interest is taxable income to the lender, and may or may not be deductible to the borrower, depending on how the loan proceeds were used. Gifts are taxable to the donor (the person giving the gift) under the gift tax, they're not a taxable income to the recipient. Some gifts are exempt or excluded from gift tax (there's the annual exemption limit, lifetime exclusion which is correlated to the estate tax, various specific purpose gifts or transfers between spouses are exempt in general). If you trade for something of equal value, is that considered income? Yes. Sale proceeds are taxable income, however your basis in the item sold is deductible from it. If you borrow a small amount of money for a short time, is that considered income? See above. Loan proceeds are not income. does the friend have to pay taxes when they get back their $10? No, repayment of the loan is not taxable income. Interest on it is. Do you have to pay taxes if you are paid back in a different format than originally paid? Form of payment doesn't matter. Barter trade doesn't affect the tax liability. The friend sold you lunches and you paid for them. The friend can deduct the cost of the lunches from the proceeds. What's left - is taxable income. Everything is translated to the functional currency at the fair market value at the time of the trade. you are required to pay taxes on the gross amount Very rarely taxes apply to gross income. Definitely not the US Federal Income taxes for individuals. An example of an exception would be the California LLC taxes. The State of California taxes LLCs under its jurisdiction on gross proceeds, regardless of the actual net income. This is very uncommon. However, the IRC (the US Federal Tax Code) is basically \"\"everything is taxable except what's not\"\", and the cost of generating income is one of the \"\"what's not\"\". That is why you can deduct the basis of the asset from your gross proceeds when you sell stuff and only pay taxes on the net difference.\"",
"title": ""
},
{
"docid": "257894",
"text": "\"In general taking money out of a 401k to repay a loan is a bad idea for a number of reasons. Taxes and penalties if you are under 59 and 1/2 you will pay a 10% penalty on withdrawals from a traditional 401k plan. Then you are going add the amount you withdraw to your income in determining your current tax bill. If you make a large withdrawal you will likely push yourself into a higher tax bracket and will end up paying additional taxes than if you made several smaller withdrawals or waited until retirement when your income would presumably be lower. Taxes and penalties will mean you will need to withdraw ~225k in order to pay taxes and penalties while still having 150k to pay toward the mortgage (this assumes you are single and have no other income). You miss out on the growth your 401k could have had. Lack of diversification the average person has the majority of their net worth tied up in their home and by paying off your mortgage you are putting even more of your money into residential real estate. By moving money from a 401k to your personal residence you could also lose some protection from creditors and lawsuits. Retirement accounts are generally off limits to creditors where as your house is limited by the homestead exemption (varies greatly from state to state). There are a few times when it might makes sense to use 401k money to pay off a mortgage. If you are older than 59.5 and have little tolerance for risk it might make sense to take the amount of money between your current income and the next higher tax bracket and \"\"invest\"\" the money in your mortgage each year. You would still want to avoid taking out a large chunk at one time though to avoid pushing yourself into a much higher tax bracket.\"",
"title": ""
}
] |
998
|
Pyridostatin prevents double-strand breaks accumulation.
|
[
{
"docid": "16472469",
"text": "G-quadruplex (G4)-forming genomic sequences, including telomeres, represent natural replication fork barriers. Stalled replication forks can be stabilized and restarted by homologous recombination (HR), which also repairs DNA double-strand breaks (DSBs) arising at collapsed forks. We have previously shown that HR facilitates telomere replication. Here, we demonstrate that the replication efficiency of guanine-rich (G-rich) telomeric repeats is decreased significantly in cells lacking HR. Treatment with the G4-stabilizing compound pyridostatin (PDS) increases telomere fragility in BRCA2-deficient cells, suggesting that G4 formation drives telomere instability. Remarkably, PDS reduces proliferation of HR-defective cells by inducing DSB accumulation, checkpoint activation, and deregulated G2/M progression and by enhancing the replication defect intrinsic to HR deficiency. PDS toxicity extends to HR-defective cells that have acquired olaparib resistance through loss of 53BP1 or REV7. Altogether, these results highlight the therapeutic potential of G4-stabilizing drugs to selectively eliminate HR-compromised cells and tumors, including those resistant to PARP inhibition.",
"title": "Targeting BRCA1 and BRCA2 Deficiencies with G-Quadruplex-Interacting Compounds"
}
] |
[
{
"docid": "10874408",
"text": "DNA double-strand breaks (DSBs), which are formed by the Spo11 protein, initiate meiotic recombination. Previous DSB-mapping studies have used rad50S or sae2Δ mutants, which are defective in break processing, to accumulate Spo11-linked DSBs, and report large (≥ 50 kb) “DSB-hot” regions that are separated by “DSB-cold” domains of similar size. Substantial recombination occurs in some DSB-cold regions, suggesting that DSB patterns are not normal in rad50S or sae2Δ mutants. We therefore developed a novel method to map genome-wide, single-strand DNA (ssDNA)–associated DSBs that accumulate in processing-capable, repair-defective dmc1Δ and dmc1Δ rad51Δ mutants. DSBs were observed at known hot spots, but also in most previously identified “DSB-cold” regions, including near centromeres and telomeres. Although approximately 40% of the genome is DSB-cold in rad50S mutants, analysis of meiotic ssDNA from dmc1Δ shows that most of these regions have substantial DSB activity. Southern blot assays of DSBs in selected regions in dmc1Δ, rad50S, and wild-type cells confirm these findings. Thus, DSBs are distributed much more uniformly than was previously believed. Comparisons of DSB signals in dmc1, dmc1 rad51, and dmc1 spo11 mutant strains identify Dmc1 as a critical strand-exchange activity genome-wide, and confirm previous conclusions that Spo11-induced lesions initiate all meiotic recombination.",
"title": "Mapping Meiotic Single-Strand DNA Reveals a New Landscape of DNA Double-Strand Breaks in Saccharomyces cerevisiae"
},
{
"docid": "20420780",
"text": "DNA double-strand breaks (DSBs) are repaired via nonhomologous end-joining (NHEJ) or homologous recombination (HR), but cellular repair processes remain elusive. We show here that the ATP-dependent chromatin-remodeling factors, ACF1 and SNF2H, accumulate rapidly at DSBs and are required for DSB repair in human cells. If the expression of ACF1 or SNF2H is suppressed, cells become extremely sensitive to X-rays and chemical treatments producing DSBs, and DSBs remain unrepaired. ACF1 interacts directly with KU70 and is required for the accumulation of KU proteins at DSBs. The KU70/80 complex becomes physically more associated with the chromatin-remodeling factors of the CHRAC complex, which includes ACF1, SNF2H, CHRAC15, and CHRAC17, after treatments producing DSBs. Furthermore, the frequency of NHEJ as well as HR induced by DSBs in chromosomal DNA is significantly decreased in cells depleted of either of these factors. Thus, ACF1 and its complexes play important roles in DSBs repair.",
"title": "The ACF1 complex is required for DNA double-strand break repair in human cells."
},
{
"docid": "21793890",
"text": "The oncogenic BCR/ABL tyrosine kinase facilitates the repair of DNA double-strand breaks (DSBs). We find that after gamma-irradiation BCR/ABL-positive leukemia cells accumulate more DSBs in comparison to normal cells. These lesions are efficiently repaired in a time-dependent fashion by BCR/ABL-stimulated non-homologous end-joining (NHEJ) followed by homologous recombination repair (HRR) mechanisms. However, mutations and large deletions were detected in HRR and NHEJ products, respectively, in BCR/ABL-positive leukemia cells. We propose that unfaithful repair of DSBs may contribute to genomic instability in the Philadelphia chromosome-positive leukemias.",
"title": "BCR/ABL modifies the kinetics and fidelity of DNA double-strand breaks repair in hematopoietic cells."
},
{
"docid": "27635177",
"text": "Mammalian DNA polymerase mu (pol mu) is related to terminal deoxynucleotidyl transferase, but its biological role is not yet clear. We show here that after exposure of cells to ionizing radiation (IR), levels of pol mu protein increase. pol mu also forms discrete nuclear foci after IR, and these foci are largely coincident with IR-induced foci of gammaH2AX, a previously characterized marker of sites of DNA double-strand breaks. pol mu is thus part of the cellular response to DNA double-strand breaks. pol mu also associates in cell extracts with the nonhomologous end-joining repair factor Ku and requires both Ku and another end-joining factor, XRCC4-ligase IV, to form a stable complex on DNA in vitro. pol mu in turn facilitates both stable recruitment of XRCC4-ligase IV to Ku-bound DNA and ligase IV-dependent end joining. In contrast, the related mammalian DNA polymerase beta does not form a complex with Ku and XRCC4-ligase IV and is less effective than pol mu in facilitating joining mediated by these factors. Our data thus support an important role for pol mu in the end-joining pathway for repair of double-strand breaks.",
"title": "Association of DNA polymerase mu (pol mu) with Ku and ligase IV: role for pol mu in end-joining double-strand break repair."
},
{
"docid": "10015292",
"text": "Highly regenerative tissues such as blood must possess effective DNA damage responses (DDR) that balance long-term regeneration with protection from leukemogenesis. Hematopoietic stem cells (HSCs) sustain life-long blood production, yet their response to DNA damage remains largely unexplored. We report that human HSCs exhibit delayed DNA double-strand break rejoining, persistent gammaH2AX foci, and enhanced p53- and ASPP1-dependent apoptosis after gamma-radiation compared to progenitors. p53 inactivation or Bcl-2 overexpression reduced radiation-induced apoptosis and preserved in vivo repopulating HSC function. Despite similar protection from irradiation-induced apoptosis, only Bcl-2-overexpressing HSCs showed higher self-renewal capacity, establishing that intact p53 positively regulates self-renewal independently from apoptosis. The reduced self-renewal of HSCs with inactivated p53 was associated with increased spontaneous gammaH2AX foci in secondary transplants of HSCs. Our data reveal distinct physiological roles of p53 that together ensure optimal HSC function: apoptosis regulation and prevention of gammaH2AX foci accumulation upon HSC self-renewal.",
"title": "A distinctive DNA damage response in human hematopoietic stem cells reveals an apoptosis-independent role for p53 in self-renewal."
},
{
"docid": "1941721",
"text": "Cells deficient in a major DNA double-strand break repair pathway (nonhomologous DNA end joining [NHEJ]) have increased spontaneous chromosome breaks; however, the source of these chromosome breaks has remained undefined. Here, we show that the observed spontaneous chromosome breaks are partially suppressed by reducing the cellular oxygen tension. Conversely, elevating the level of reactive oxygen species by overexpressing the antioxidant enzyme superoxide dismutase 1 (SOD1), in a transgenic mouse, increases chromosome breakage. The effect of SOD1 can also be modulated by cellular oxygen tension. The elevated chromosome breakage correlates histologically with a significant increase in the amount of neuronal cell death in Ku86(-/-) SOD1 transgenic embryos over that seen in Ku86(-/-) embryos. Therefore, oxygen metabolism is a major source of the genomic instability observed in NHEJ-deficient cells and, presumably, in all cells.",
"title": "Oxygen Metabolism Causes Chromosome Breaks and Is Associated with the Neuronal Apoptosis Observed in DNA Double-Strand Break Repair Mutants"
},
{
"docid": "14178995",
"text": "The genetic diseases Hutchinson-Gilford progeria syndrome (HGPS) and restrictive dermopathy (RD) arise from accumulation of farnesylated prelamin A because of defects in the lamin A maturation pathway. Both of these diseases exhibit symptoms that can be viewed as accelerated aging. The mechanism by which accumulation of farnesylated prelamin A leads to these accelerated aging phenotypes is not understood. Here we present evidence that in HGPS and RD fibroblasts, DNA damage checkpoints are persistently activated because of the compromise in genomic integrity. Inactivation of checkpoint kinases Ataxia-telangiectasia-mutated (ATM) and ATR (ATM- and Rad3-related) in these patient cells can partially overcome their early replication arrest. Treatment of patient cells with a protein farnesyltransferase inhibitor (FTI) did not result in reduction of DNA double-strand breaks and damage checkpoint signaling, although the treatment significantly reversed the aberrant shape of their nuclei. This suggests that DNA damage accumulation and aberrant nuclear morphology are independent phenotypes arising from prelamin A accumulation in these progeroid syndromes. Since DNA damage accumulation is an important contributor to the symptoms of HGPS, our results call into question the possibility of treatment of HGPS with FTIs alone.",
"title": "Summary"
},
{
"docid": "4444861",
"text": "Cells deficient in the Brca1 and Brca2 genes have reduced capacity to repair DNA double-strand breaks by homologous recombination and consequently are hypersensitive to DNA-damaging agents, including cisplatin and poly(ADP-ribose) polymerase (PARP) inhibitors. Here we show that loss of the MLL3/4 complex protein, PTIP, protects Brca1/2-deficient cells from DNA damage and rescues the lethality of Brca2-deficient embryonic stem cells. However, PTIP deficiency does not restore homologous recombination activity at double-strand breaks. Instead, its absence inhibits the recruitment of the MRE11 nuclease to stalled replication forks, which in turn protects nascent DNA strands from extensive degradation. More generally, acquisition of PARP inhibitors and cisplatin resistance is associated with replication fork protection in Brca2-deficient tumour cells that do not develop Brca2 reversion mutations. Disruption of multiple proteins, including PARP1 and CHD4, leads to the same end point of replication fork protection, highlighting the complexities by which tumour cells evade chemotherapeutic interventions and acquire drug resistance.",
"title": "Replication Fork Stability Confers Chemoresistance in BRCA-deficient Cells"
},
{
"docid": "22937815",
"text": "Now that we have a good understanding of the DNA double strand break (DSB) repair mechanisms and DSB-induced damage signalling, attention is focusing on the changes to the chromatin environment needed for efficient DSB repair. Mutations in chromatin remodelling complexes have been identified in cancers, making it important to evaluate how they impact upon genomic stability. Our current understanding of the DSB repair pathways suggests that each one has distinct requirements for chromatin remodelling. Moreover, restricting the extent of chromatin modifications could be a significant factor regulating the decision of pathway usage. In this review, we evaluate the distinct DSB repair pathways for their potential need for chromatin remodelling and review the roles of ATP-driven chromatin remodellers in the pathways.",
"title": "Roles of chromatin remodellers in DNA double strand break repair."
},
{
"docid": "11568270",
"text": "Human TopBP1 is a major player in the control of the DNA replication checkpoint. In this study, we identified MDC1, a key checkpoint protein involved in the cellular response to DNA double-strand breaks, as a TopBP1-associated protein. The specific TopBP1-MDC1 interaction is mediated by the fifth BRCT domain of TopBP1 and the Ser-Asp-Thr (SDT) repeats of MDC1. In addition, we demonstrated that TopBP1 accumulation at stalled replication forks is promoted by the H2AX/MDC1 signaling cascade. Moreover, MDC1 is important for ATR-dependent Chk1 activation in response to replication stress. Collectively, our data suggest that MDC1 facilitates several important steps in both cellular DNA damage response and the DNA replication checkpoint.",
"title": "MDC1 collaborates with TopBP1 in DNA replication checkpoint control"
},
{
"docid": "30122260",
"text": "DNA double-strand breaks (DSBs) are highly hazardous for genome integrity because they have the potential to cause mutations, chromosomal rearrangements and genomic instability. The cellular response to DSBs is orchestrated by signal transduction pathways, known as DNA damage checkpoints, which are conserved from yeasts to humans. These pathways can sense DNA damage and transduce this information to specific cellular targets, which in turn regulate cell cycle transitions and DNA repair. The mammalian protein kinases ATM and ATR, as well as their budding yeast corresponding orthologs Tel1 and Mec1, act as master regulators of the checkpoint response to DSBs. Here, we review the early steps of DSB processing and the role of DNA-end structures in activating ATM/Tel1 and ATR/Mec1 in an orderly and reciprocal manner.",
"title": "Interplays between ATM/Tel1 and ATR/Mec1 in sensing and signaling DNA double-strand breaks."
},
{
"docid": "3512154",
"text": "CRISPR-Cas (clustered, regularly interspaced short palindromic repeats coupled with CRISPR-associated proteins) is a bacterial immunity system that protects against invading phages or plasmids. In the process of CRISPR adaptation, short pieces of DNA ('spacers') are acquired from foreign elements and integrated into the CRISPR array. So far, it has remained a mystery how spacers are preferentially acquired from the foreign DNA while the self chromosome is avoided. Here we show that spacer acquisition is replication-dependent, and that DNA breaks formed at stalled replication forks promote spacer acquisition. Chromosomal hotspots of spacer acquisition were confined by Chi sites, which are sequence octamers highly enriched on the bacterial chromosome, suggesting that these sites limit spacer acquisition from self DNA. We further show that the avoidance of self is mediated by the RecBCD double-stranded DNA break repair complex. Our results suggest that, in Escherichia coli, acquisition of new spacers largely depends on RecBCD-mediated processing of double-stranded DNA breaks occurring primarily at replication forks, and that the preference for foreign DNA is achieved through the higher density of Chi sites on the self chromosome, in combination with the higher number of forks on the foreign DNA. This model explains the strong preference to acquire spacers both from high copy plasmids and from phages.",
"title": "CRISPR adaptation biases explain preference for acquisition of foreign DNA"
},
{
"docid": "13023410",
"text": "The oncogenic BCR/ABL tyrosine kinase induces constitutive DNA damage in Philadelphia chromosome (Ph)-positive leukemia cells. We find that BCR/ABL-induced reactive oxygen species (ROSs) cause chronic oxidative DNA damage resulting in double-strand breaks (DSBs) in S and G(2)/M cell cycle phases. These lesions are repaired by BCR/ABL-stimulated homologous recombination repair (HRR) and nonhomologous end-joining (NHEJ) mechanisms. A high mutation rate is detected in HRR products in BCR/ABL-positive cells, but not in the normal counterparts. In addition, large deletions are found in NHEJ products exclusively in BCR/ABL cells. We propose that the following series of events may contribute to genomic instability of Ph-positive leukemias: BCR/ABL --> ROSs --> oxidative DNA damage --> DSBs in proliferating cells --> unfaithful HRR and NHEJ repair.",
"title": "BCR/ABL oncogenic kinase promotes unfaithful repair of the reactive oxygen species-dependent DNA double-strand breaks."
},
{
"docid": "44172171",
"text": "The RNA-guided DNA endonuclease Cas9 is a powerful tool for genome editing. Little is known about the kinetics and fidelity of the double-strand break (DSB) repair process that follows a Cas9 cutting event in living cells. Here, we developed a strategy to measure the kinetics of DSB repair for single loci in human cells. Quantitative modeling of repaired DNA in time series after Cas9 activation reveals variable and often slow repair rates, with half-life times up to ∼10 hr. Furthermore, repair of the DSBs tends to be error prone. Both classical and microhomology-mediated end joining pathways contribute to the erroneous repair. Estimation of their individual rate constants indicates that the balance between these two pathways changes over time and can be altered by additional ionizing radiation. Our approach provides quantitative insights into DSB repair kinetics and fidelity in single loci and indicates that Cas9-induced DSBs are repaired in an unusual manner.",
"title": "Kinetics and Fidelity of the Repair of Cas9-Induced Double-Strand DNA Breaks"
},
{
"docid": "12552297",
"text": "DNA polymerase lambda (polλ) is a recently identified DNA polymerase whose cellular function remains elusive. Here we show, that polλ participates at the molecular level in a chromosomal context, in the repair of DNA double strand breaks (DSB) via non-homologous end joining (NHEJ) in mammalian cells. The expression of a catalytically inactive form of polλ (polλDN) decreases the frequency of NHEJ events in response to I-Sce-I-induced DSB whereas inactivated forms of its homologues polβ and polμ do not. Only events requiring DNA end processing before ligation are affected; this defect is associated with large deletions arising in the vicinity of the induced DSB. Furthermore, polλDN-expressing cells exhibit increased sensitization and genomic instability in response to ionizing radiation similar to that of NHEJ-defective cells. Our data support a requirement for polλ in repairing a subset of DSB in genomic DNA, thereby contributing to the maintenance of genetic stability mediated by the NHEJ pathway.",
"title": "The DNA polymerase λ is required for the repair of non-compatible DNA double strand breaks by NHEJ in mammalian cells"
},
{
"docid": "14446279",
"text": "In the yeast Saccharomyces cerevisiae that lacks lamins, the nuclear pore complex (NPC) has been proposed to serve a role in chromatin organization. Here, using fluorescence microscopy in living cells, we show that nuclear pore proteins of the Nup84 core complex, Nup84p, Nup145Cp, Nup120p, and Nup133p, serve to anchor telomere XI-L at the nuclear periphery. The integrity of this complex is shown to be required for repression of a URA3 gene inserted in the subtelomeric region of this chromosome end. Furthermore, altering the integrity of this complex decreases the efficiency of repair of a DNA double-strand break (DSB) only when it is generated in the subtelomeric region, even though the repair machinery is functional. These effects are specific to the Nup84 complex. Our observations thus confirm and extend the role played by the NPC, through the Nup84 complex, in the functional organization of chromatin. They also indicate that anchoring of telomeres is essential for efficient repair of DSBs occurring therein and is important for preserving genome integrity.",
"title": "Telomere tethering at the nuclear periphery is essential for efficient DNA double strand break repair in subtelomeric region"
},
{
"docid": "12909503",
"text": "DNA damage encountered by DNA replication forks poses risks of genome destabilization, a precursor to carcinogenesis. Damage checkpoint systems cause cell cycle arrest, promote repair and induce programed cell death when damage is severe. Checkpoints are critical parts of the DNA damage response network that act to suppress cancer. DNA damage and perturbation of replication machinery causes replication stress, characterized by accumulation of single-stranded DNA bound by replication protein A (RPA), which triggers activation of ataxia telangiectasia and Rad3 related (ATR) and phosphorylation of the RPA32, subunit of RPA, leading to Chk1 activation and arrest. DNA-dependent protein kinase catalytic subunit (DNA-PKcs) [a kinase related to ataxia telangiectasia mutated (ATM) and ATR] has well characterized roles in DNA double-strand break repair, but poorly understood roles in replication stress-induced RPA phosphorylation. We show that DNA-PKcs mutant cells fail to arrest replication following stress, and mutations in RPA32 phosphorylation sites targeted by DNA-PKcs increase the proportion of cells in mitosis, impair ATR signaling to Chk1 and confer a G2/M arrest defect. Inhibition of ATR and DNA-PK (but not ATM), mimic the defects observed in cells expressing mutant RPA32. Cells expressing mutant RPA32 or DNA-PKcs show sustained H2AX phosphorylation in response to replication stress that persists in cells entering mitosis, indicating inappropriate mitotic entry with unrepaired damage.",
"title": "Distinct roles for DNA-PK, ATM and ATR in RPA phosphorylation and checkpoint activation in response to replication stress"
},
{
"docid": "12207340",
"text": "The repair of DNA double-strand breaks (DSBs) by homologous recombination (HR) is initiated by nucleolytic degradation of the 5'-terminated strands in a process termed end resection. End resection generates 3'-single-stranded DNA tails, substrates for Rad51 to catalyze homologous pairing and DNA strand exchange, and for activation of the DNA damage checkpoint. The commonly accepted view is that end resection occurs by a two-step mechanism. In the first step, Sae2/CtIP activates the Mre11-Rad50-Xrs2/Nbs1 (MRX/N) complex to endonucleolytically cleave the 5'-terminated DNA strands close to break ends, and in the second step Exo1 and/or Dna2 nucleases extend the resected tracts to produce long 3'-ssDNA-tailed intermediates. Initiation of resection commits a cell to repair a DSB by HR because long ssDNA overhangs are poor substrates for non-homologous end joining (NHEJ). Thus, the initiation of end resection has emerged as a critical control point for repair pathway choice. Here, I review recent studies on the mechanism of end resection and how this process is regulated to ensure the most appropriate repair outcome.",
"title": "Mechanism and regulation of DNA end resection in eukaryotes."
},
{
"docid": "30353437",
"text": "Ataxia telangiectasia (AT) has long intrigued the biomedical research community owing to the spectrum of defects that are characteristic of the disease, including neurodegeneration, immune dysfunction, radiosensitivity and cancer predisposition. Following the identification of mutations in ATM (ataxia telangiectasia, mutated) as the underlying cause of the disease, biochemical analysis of this protein kinase has shown that it is a crucial nexus for the cellular response to DNA double-stranded breaks. Many ATM kinase substrates are important players in the cellular responses that prevent cancer. Accordingly, AT is a disease that results from defects in the response to specific types of DNA damage. Thus, although it is a rare neurodegenerative disease, understanding the biology of AT will lead to a greater understanding of the fundamental processes that underpin cancer and neurodegeneration.",
"title": "ATM and ataxia telangiectasia."
},
{
"docid": "21221346",
"text": "In eukaryotic cells, nonhomologous DNA end joining (NHEJ) is a major pathway for repair of double-strand DNA breaks (DSBs). Artemis and the 469kDa DNA-dependent protein kinase (DNA-PKcs) together form a key nuclease for NHEJ in vertebrate organisms. The structure-specific endonucleolytic activity of Artemis is activated by binding to and phosphorylation by DNA-PKcs. We tested various DNA structures in order to understand the range of structural features that are recognized by the Artemis:DNA-PKcs complex. We find that all tested substrates that contain single-to-double-strand transitions can be cleaved by the Artemis:DNA-PKcs complex near the transition region. The cleaved substrates include heterologous loops, stem-loops, flaps, and gapped substrates. Such versatile activity on single-/double-strand transition regions is important in understanding how reconstituted NHEJ systems that lack DNA polymerases can join incompatible DNA ends and yet preserve 3' overhangs. Additionally, the flexibility of the Artemis:DNA-PKcs nuclease may be important in removing secondary structures that hinder processing of DNA ends during NHEJ.",
"title": "The Artemis:DNA-PKcs endonuclease cleaves DNA loops, flaps, and gaps."
},
{
"docid": "25462689",
"text": "We have investigated HO endonuclease-induced double-strand break (DSB) recombination and repair in a LACZ duplication plasmid in yeast. A 117-bp MATa fragment, embedded in one copy of LACZ, served as a site for initiation of a DSB when HO endonuclease was expressed. The DSB could be repaired using wild-type sequences located on a second, promoterless, copy of LACZ on the same plasmid. In contrast to normal mating-type switching, crossing-over associated with gene conversion occurred at least 50% of the time. The proportion of conversion events accompanied by exchange was greater when the two copies of LACZ were in direct orientation (80%), than when inverted (50%). In addition, the fraction of plasmids lost was significantly greater in the inverted orientation. The kinetics of appearance of intermediates and final products were also monitored. The repair of the DSB is slow, requiring at least an hour from the detection of the HO-cut fragments to completion of repair. Surprisingly, the appearance of the two reciprocal products of crossing over did not occur with the same kinetics. For example, when the two LACZ sequences were in the direct orientation, the HO-induced formation of a large circular deletion product was not accompanied by the appearance of a small circular reciprocal product. We suggest that these differences may reflect two kinetically separable processes, one involving only one cut end and the other resulting from the concerted participation of both ends of the DSB.",
"title": "Genetic and physical analysis of double-strand break repair and recombination in Saccharomyces cerevisiae."
},
{
"docid": "8577229",
"text": "Recombination-dependent DNA replication, often called break-induced replication (BIR), was initially invoked to explain recombination events in bacteriophage but it has recently been recognized as a fundamentally important mechanism to repair double-strand chromosome breaks in eukaryotes. This mechanism appears to be critically important in the restarting of stalled and broken replication forks and in maintaining the integrity of eroded telomeres. Although BIR helps preserve genome integrity during replication, it also promotes genome instability by the production of loss of heterozygosity and the formation of nonreciprocal translocations, as well as in the generation of complex chromosomal rearrangements.",
"title": "Break-induced DNA replication."
},
{
"docid": "4401289",
"text": "Homology-directed DNA repair is essential for genome maintenance through templated DNA synthesis. Alternative lengthening of telomeres (ALT) necessitates homology-directed DNA repair to maintain telomeres in about 10–15% of human cancers. How DNA damage induces assembly and execution of a DNA replication complex (break-induced replisome) at telomeres or elsewhere in the mammalian genome is poorly understood. Here we define break-induced telomere synthesis and demonstrate that it utilizes a specialized replisome, which underlies ALT telomere maintenance. DNA double-strand breaks enact nascent telomere synthesis by long-tract unidirectional replication. Proliferating cell nuclear antigen (PCNA) loading by replication factor C (RFC) acts as the initial sensor of telomere damage to establish predominance of DNA polymerase δ (Pol δ) through its POLD3 subunit. Break-induced telomere synthesis requires the RFC–PCNA–Pol δ axis, but is independent of other canonical replisome components, ATM and ATR, or the homologous recombination protein Rad51. Thus, the inception of telomere damage recognition by the break-induced replisome orchestrates homology-directed telomere maintenance.",
"title": "Break-induced telomere synthesis underlies alternative telomere maintenance"
},
{
"docid": "2904102",
"text": "RecQ family helicases function as safeguards of the genome. Unlike Escherichia coli, the Gram-positive Bacillus subtilis bacterium possesses two RecQ-like homologues, RecQ[Bs] and RecS, which are required for the repair of DNA double-strand breaks. RecQ[Bs] also binds to the forked DNA to ensure a smooth progression of the cell cycle. Here we present the first biochemical analysis of recombinant RecQ[Bs]. RecQ[Bs] binds weakly to single-stranded DNA (ssDNA) and blunt-ended double-stranded DNA (dsDNA) but strongly to forked dsDNA. The protein exhibits a DNA-stimulated ATPase activity and ATP- and Mg(2+)-dependent DNA helicase activity with a 3' → 5' polarity. Molecular modeling shows that RecQ[Bs] shares high sequence and structure similarity with E. coli RecQ. Surprisingly, RecQ[Bs] resembles the truncated Saccharomyces cerevisiae Sgs1 and human RecQ helicases more than RecQ[Ec] with regard to its enzymatic activities. Specifically, RecQ[Bs] unwinds forked dsDNA and DNA duplexes with a 3'-overhang but is inactive on blunt-ended dsDNA and 5'-overhung duplexes. Interestingly, RecQ[Bs] unwinds blunt-ended DNA with structural features, including nicks, gaps, 5'-flaps, Kappa joints, synthetic replication forks, and Holliday junctions. We discuss these findings in the context of RecQ[Bs]'s possible functions in preserving genomic stability.",
"title": "Characterization of biochemical properties of Bacillus subtilis RecQ helicase."
},
{
"docid": "15472716",
"text": "DNA-PKcs and Ku are essential components of the complex that catalyzes non-homologous end joining (NHEJ) of DNA double-strand breaks (DSBs). Ku, a heterodimeric protein, binds to DNA ends and facilitates recruitment of the catalytic subunit, DNA-PKcs. We have investigated the effect of DNA strand orientation and sequence bias on the activation of DNA-PK. In addition, we assessed the effect of the position and strand orientation of cisplatin adducts on kinase activation. A series of duplex DNA substrates with site-specific cisplatin–DNA adducts placed in three different orientations on the duplex DNA were prepared. Terminal biotin modification and streptavidin (SA) blocking was employed to direct DNA-PK binding to the unblocked termini with a specific DNA strand orientation and cisplatin–DNA adduct position. DNA-PK kinase activity was measured and the results reveal that DNA strand orientation and sequence bias dramatically influence kinase activation, only a portion of which could be attributed to Ku-DNA binding activity. In addition, cisplatin–DNA adduct position resulted in differing degrees of inhibition depending on distance from the terminus as well as strand orientation. These results highlight the importance of how local variations in DNA structure, chemistry and sequence influence DNA-PK activation and potentially NHEJ.",
"title": "Differential activation of DNA-PK based on DNA strand orientation and sequence bias"
},
{
"docid": "18144189",
"text": "DNA topoisomerases solve the topological problems associated with DNA replication, transcription, recombination, and chromatin remodeling by introducing temporary single- or double-strand breaks in the DNA. In addition, these enzymes fine-tune the steady-state level of DNA supercoiling both to facilitate protein interactions with the DNA and to prevent excessive supercoiling that is deleterious. In recent years, the crystal structures of a number of topoisomerase fragments, representing nearly all the known classes of enzymes, have been solved. These structures provide remarkable insights into the mechanisms of these enzymes and complement previous conclusions based on biochemical analyses. Surprisingly, despite little or no sequence homology, both type IA and type IIA topoisomerases from prokaryotes and the type IIA enzymes from eukaryotes share structural folds that appear to reflect functional motifs within critical regions of the enzymes. The type IB enzymes are structurally distinct from all other known topoisomerases but are similar to a class of enzymes referred to as tyrosine recombinases. The structural themes common to all topoisomerases include hinged clamps that open and close to bind DNA, the presence of DNA binding cavities for temporary storage of DNA segments, and the coupling of protein conformational changes to DNA rotation or DNA movement. For the type II topoisomerases, the binding and hydrolysis of ATP further modulate conformational changes in the enzymes to effect changes in DNA topology.",
"title": "DNA topoisomerases: structure, function, and mechanism."
},
{
"docid": "7151961",
"text": "Double-strand breaks (DSBs) occur frequently during DNA replication. They are also caused by ionizing radiation, chemical damage or as part of the series of programmed events that occur during meiosis. In yeast, DSB repair requires RAD52, a protein that plays a critical role in homologous recombination. Here we describe the actions of human RAD52 protein in a model system for single-strand annealing (SSA) using tailed (i.e. exonuclease resected) duplex DNA molecules. Purified human RAD52 protein binds resected DSBs and promotes associations between complementary DNA termini. Heteroduplex intermediates of these recombination reactions have been visualized by electron microscopy, revealing the specific binding of multiple rings of RAD52 to the resected termini and the formation of large protein complexes at heteroduplex joints formed by RAD52-mediated annealing.",
"title": "Visualization of recombination intermediates produced by RAD52-mediated single-strand annealing."
},
{
"docid": "236204",
"text": "In many eukaryotes, RNA-dependent RNA polymerases (RdRPs) play key roles in the RNAi pathway. They have been implicated in the recognition and processing of aberrant transcripts triggering the process, and in amplification of the silencing response. We have tested the functions of RdRP genes from the ciliate Paramecium tetraurelia in experimentally induced and endogenous mechanisms of gene silencing. In this organism, RNAi can be triggered either by high-copy, truncated transgenes or by directly feeding cells with double-stranded RNA (dsRNA). Surprisingly, dsRNA-induced silencing depends on the putatively functional RDR1 and RDR2 genes, which are required for the accumulation of both primary siRNAs and a distinct class of small RNAs suggestive of secondary siRNAs. In contrast, a third gene with a highly divergent catalytic domain, RDR3, is required for siRNA accumulation when RNAi is triggered by truncated transgenes. Our data further implicate RDR3 in the accumulation of previously described endogenous siRNAs and in the regulation of the surface antigen gene family. While only one of these genes is normally expressed in any clonal cell line, the knockdown of RDR3 leads to co-expression of multiple antigens. These results provide evidence for a functional specialization of Paramecium RdRP genes in distinct RNAi pathways operating during vegetative growth.",
"title": "Distinct RNA-dependent RNA polymerases are required for RNAi triggered by double-stranded RNA versus truncated transgenes in Paramecium tetraurelia"
},
{
"docid": "20821402",
"text": "Nonhomologous end joining (NHEJ) is essential for efficient repair of chromosome breaks. However, the NHEJ ligation step is often obstructed by break-associated nucleotide damage, including base loss (abasic site or 5'-dRP/AP sites). Ku, a 5'-dRP/AP lyase, can excise such damage at ends in preparation for the ligation step. We show here that this activity is greatest if the abasic site is within a short 5' overhang, when this activity is necessary and sufficient to prepare such termini for ligation. In contrast, Ku is less active near 3' strand termini, where excision would leave a ligation-blocking α,β-unsaturated aldehyde. The Ku AP lyase activity is also strongly suppressed by as little as two paired bases 5' of the abasic site. Importantly, in vitro end joining experiments show that abasic sites significantly embedded in double-stranded DNA do not block the NHEJ ligation step. Suppression of the excision activity of Ku in this context therefore is not essential for ligation and further helps NHEJ retain terminal sequence in junctions. We show that the DNA between the 5' terminus and the abasic site can also be retained in junctions formed by cellular NHEJ, indicating that these sites are at least partly resistant to other abasic site-cleaving activities as well. High levels of the 5'-dRP/AP lyase activity of Ku are thus restricted to substrates where excision of an abasic site is required for ligation, a degree of specificity that promotes more accurate joining.",
"title": "Specificity of the dRP/AP lyase of Ku promotes nonhomologous end joining (NHEJ) fidelity at damaged ends."
},
{
"docid": "5572127",
"text": "The role of ataxia telangiectasia mutated (ATM), a DNA double-strand break recognition and response protein, in inflammation and inflammatory diseases is unclear. We have previously shown that high levels of systemic DNA damage are induced by intestinal inflammation in wild-type mice. To determine the effect of Atm deficiency in inflammation, we induced experimental colitis in Atm(-/-), Atm(+/-), and wild-type mice via dextran sulfate sodium (DSS) administration. Atm(-/-) mice had higher disease activity indices and rates of mortality compared with heterozygous and wild-type mice. Systemic DNA damage and immune response were characterized in peripheral blood throughout and after three cycles of treatment. Atm(-/-) mice showed increased sensitivity to levels of DNA strand breaks in peripheral leukocytes, as well as micronucleus formation in erythroblasts, compared with heterozygous and wild-type mice, especially during remission periods and after the end of treatment. Markers of reactive oxygen and nitrogen species-mediated damage, including 8-oxoguanine and nitrotyrosine, were present both in the distal colon and in peripheral leukocytes, with Atm(-/-) mice manifesting more 8-oxoguanine formation than wild-type mice. Atm(-/-) mice showed greater upregulation of inflammatory cytokines and significantly higher percentages of activated CD69+ and CD44+ T cells in the peripheral blood throughout treatment. ATM, therefore, may be a critical immunoregulatory factor dampening the deleterious effects of chronic DSS-induced inflammation, necessary for systemic genomic stability and homeostasis of the gut epithelial barrier.",
"title": "Atm-deficient mice exhibit increased sensitivity to dextran sulfate sodium-induced colitis characterized by elevated DNA damage and persistent immune activation."
}
] |
8761
|
What happens to an ETF if one of the companies in the ETF gets aquired?
|
[
{
"docid": "325818",
"text": "There are a number of ways this can result. In a broad ETF, such as SPY, the S&P 500 spider, the S&P index will have 500 stocks no matter what, so a buyout would simply result in a re-shuffling of the index makeup. No buyout will happen so quickly that there's no time to choose the next stock to join the index. In your case, if the fund manager (per the terms of the prospectus) wishes to simply reallocate the index to remove the taken-over stock that's probably how he handle it. Unless of course, the prospectus dictates otherwise. In which case, a cash dividend is a possible alternative.",
"title": ""
}
] |
[
{
"docid": "410061",
"text": "You do not hold leveraged ETF for longer than a few days. You have UGAZ and DGAZ, both 3x leveraged, one longs one shorts. What happens if you buy both? You don't get 0% return. In fact, you get -10% return if you hold both for 3 months. No matter what happens, they both go down in long term. Call it Leverage Decay, Beta Slippage, Contango, Rollover, etc. If you want to gamble that NG goes up within 3 days, go ahead. Just be prepared for the worst cases like losing 15% in 3 days. If you want to speculate the NG will recover in a year, buy Natural Gas industry ETF http://www.ftportfolios.com/retail/etf/etfsummary.aspx?Ticker=FCG",
"title": ""
},
{
"docid": "183898",
"text": "It is true that this is possible, however, it's very remote in the case of the large and reputable fund companies such as Vanguard. FDIC insurance protects against precisely this for bank accounts, but mutual funds and ETFs do not have an equivalent to FDIC insurance. One thing that does help you in the case of a mutual fund or ETF is that you indirectly (through the fund) own actual assets. In a cash account at a bank, you have a promise from the bank to pay, and then the bank can go off and use your money to make loans. You don't in any sense own the bank's loans. With a fund, the fund company cannot (legally) take your money out of the fund, except to pay the expense ratio. They have to use your money to buy stocks, bonds, or whatever the fund invests in. Those assets are then owned by the fund. Legally, a mutual fund is a special kind of company defined in the Investment Company Act of 1940, and is a separate company from the investment advisor (such as Vanguard): http://www.sec.gov/answers/mfinvco.htm Funds have their own boards, and in principle a fund board can even fire the company advising the fund, though this is not likely since boards aren't usually independent. (a quick google found this article for more, maybe someone can find a better one: http://www.marketwatch.com/story/mutual-fund-independent-board-rule-all-but-dead) If Vanguard goes under, the funds could continue to exist and get a new adviser, or could be liquidated with investors receiving whatever the assets are worth. Of course, all this legal stuff doesn't help you with outright fraud. If a fund's adviser says it bought the S&P 500, but really some guy bought himself a yacht, Madoff-style, then you have a problem. But a huge well-known ETF has auditors, tons of different employees, lots of brokerage and exchange traffic, etc. so to me at least it's tough to imagine a risk here. With a small fund company with just a few people - and there are lots of these! - then there's more risk, and you'd want to carefully look at what independent agent holds their assets, who their auditors are, and so forth. With regular mutual funds (not ETFs) there are more issues with diversifying across fund companies: With ETFs, there probably isn't much downside to diversifying since you could buy them all from one brokerage account. Maybe it even happens naturally if you pick the best ETFs you can find. Personally, I would just pick the best ETFs and not worry about advisor diversity. Update: maybe also deserving a mention are exchange-traded notes (ETNs). An ETN's legal structure is more like the bank account, minus the FDIC insurance of course. It's an IOU from the company that runs the ETN, where they promise to pay back the value of some index. There's no investment company as with a fund, and therefore you don't own a share of any actual assets. If the ETN's sponsor went bankrupt, you would indeed have a problem, much more so than if an ETF's sponsor went bankrupt.",
"title": ""
},
{
"docid": "418150",
"text": "If a stock that makes up a big part of the Dow Jones Industrial Average decided to issue a huge number of additional shares, that will make the index go up. At least this is what should happen, since an index is basically a sum of the market cap of the contributing companies. No, indices can have various weightings. The DJIA is a price-weighted index not market-cap weighted. An alternative weighting besides market-cap and price is equal weighting. From Dow Jones: Dow Jones Industrial Average™. Introduced in May 1896, the index, also referred to as The Dow®, is a price-weighted measure of 30 U.S. blue-chip companies. Thus, I can wonder what in the new shares makes the index go up? If a stock is split, the Dow divisor is adjusted as one could easily see how the current Dow value isn't equal to the sum or the share prices of the members of the index. In other cases, there may be a dilution of earnings but that doesn't necessarily affect the stock price directly as there may be options exercised or secondary offerings made. SO if the index, goes up, will the ETF DIA also go up automatically although no additional buying has happened in the ETF itself? If the index rises and the ETF doesn't proportionally, then there is an arbitrage opportunity for someone to buy the DIA shares that can be redeemed for the underlying stocks that are worth more in this case. Look at the Creation and Redemption Unit process that exists for ETFs.",
"title": ""
},
{
"docid": "370470",
"text": "An interesting read. As of lately, my office has been getting calls from Hartford, Fidelity, Oppenheimer, First Trust, and now Prudential regarding their ETFs. A lot of them just received their 3 year number and the companies are trying to get inflows into them. Prudential's has not launched yet, but is expecting to drop end of summer or early fall. Fidelity is currently the only major competitor in the space. They have a slightly lower internal cost compared to Vanguard and their position are almost identical to the iShares ETFs offered by Black Rock. You can think of Black Rock as Bounty brand paper towels while Fidelity is more like Kirkland Signature. Essentially the same thing with a slight savings on price. One thing to look out for is the very thin trading volume on some of these new ETFs. Oppenheimer and Hartford have very thin levels of volume which makes owning them feel like a game of old maid. You don't want to be stuck holding the bag if something happens in the sector ETF that was purchased. Always make sure there is a market for some of these ETFs before you buy it. Fidelity has overcome some of these volume problems... but some of the ETFs are still a little thin. Just stick with Vanguard for the thinly traded sectors and consider Fidelity if you want to shave a few bps on internal cost. This has just been my personal observation of the industry.",
"title": ""
},
{
"docid": "29184",
"text": "\"Does the bolded sentence apply for ETFs and ETF companies? No, the value of an ETF is determined by an exchange and thus the value of the share is whatever the trading price is. Thus, the price of an ETF may go up or down just like other securities. Money market funds can be a bit different as the mutual fund company will typically step in to avoid \"\"Breaking the Buck\"\" that could happen as a failure for that kind of fund. To wit, must ETF companies invest a dollar in the ETF for every dollar that an investor deposited in this aforesaid ETF? No, because an ETF is traded as shares on the market, unless you are using the creation/redemption mechanism for the ETF, you are buying and selling shares like most retail investors I'd suspect. If you are using the creation/redemption system then there are baskets of other securities that are being swapped either for shares in the ETF or from shares in the ETF.\"",
"title": ""
},
{
"docid": "224765",
"text": "\"An ETF does not track any one individual stock. It \"\"is a marketable security that tracks an index, a commodity, bonds, or a basket of assets like an index fund.\"\" Check out this link to learn more about ETFs. The easiest way see what ETF tracks a stock is to determine what sector and industry that company is in and find some ETF that trade it. The ETF will likely trade that stock, assuming that its market cap and exchange it trades on fits within the parameters of the ETF.\"",
"title": ""
},
{
"docid": "434799",
"text": "\"I'm trying to understand how an ETF manager optimized it's own revenue. Here's an example that I'm trying to figure out. ETF firm has an agreement with GS for blocks of IBM. They have agreed on daily VWAP + 1% for execution price. Further, there is a commission schedule for 5 mils with GS. Come month end, ETF firm has to do a monthly rebalance. As such must buy 100,000 shares at IBM which goes for about $100 The commission for the trade is 100,000 * 5 mils = $500 in commission for that trade. I assume all of this is covered in the expense ratio. Such that if VWAP for the day was 100, then each share got executed to the ETF at 101 (VWAP+ %1) + .0005 (5 mils per share) = for a resultant 101.0005 cost basis The ETF then turns around and takes out (let's say) 1% as the expense ratio ($1.01005 per share) I think everything so far is pretty straight forward. Let me know if I missed something to this point. Now, this is what I'm trying to get my head around. ETF firm has a revenue sharing agreement as well as other \"\"relations\"\" with GS. One of which is 50% back on commissions as soft dollars. On top of that GS has a program where if you do a set amount of \"\"VWAP +\"\" trades you are eligible for their corporate well-being programs and other \"\"sponsorship\"\" of ETF's interests including helping to pay for marketing, rent, computers, etc. Does that happen? Do these disclosures exist somewhere?\"",
"title": ""
},
{
"docid": "482399",
"text": "\"Here's an example that I'm trying to figure out. ETF firm has an agreement with GS for blocks of IBM. They have agreed on daily VWAP + 1% for execution price. Further, there is a commission schedule for 5 mils with GS. Come month end, ETF firm has to do a monthly rebalance. As such must buy 100,000 shares at IBM which goes for about $100 The commission for the trade is 100,000 * 5 mils = $500 in commission for that trade. I assume all of this is covered in the expense ratio. Such that if VWAP for the day was 100, then each share got executed to the ETF at 101 (VWAP+ %1) + .0005 (5 mils per share) = for a resultant 101.0005 cost basis The ETF then turns around and takes out (let's say) 1% as the expense ratio ($1.01005 per share) I think everything so far is pretty straight forward. Let me know if I missed something to this point. Now, this is what I'm trying to get my head around. ETF firm has a revenue sharing agreement as well as other \"\"relations\"\" with GS. One of which is 50% back on commissions as soft dollars. On top of that GS has a program where if you do a set amount of \"\"VWAP +\"\" trades you are eligible for their corporate well-being programs and other \"\"sponsorship\"\" of ETF's interests including helping to pay for marketing, rent, computers, etc. Does that happen? Do these disclosures exist somewhere?\"",
"title": ""
},
{
"docid": "332924",
"text": "\"I recommend avoiding trading directly in commodities futures and options. If you're not prepared to learn a lot about how futures markets and trading works, it will be an experience fraught with pitfalls and lost money – and I am speaking from experience. Looking at stock-exchange listed products is a reasonable approach for an individual investor desiring added diversification for their portfolio. Still, exercise caution and know what you're buying. It's easy to access many commodity-based exchange-traded funds (ETFs) on North American stock exchanges. If you already have low-cost access to U.S. markets, consider this option – but be mindful of currency conversion costs, etc. Yet, there is also a European-based company, ETF Securities, headquartered in Jersey, Channel Islands, which offers many exchange-traded funds on European exchanges such as London and Frankfurt. ETF Securities started in 2003 by first offering a gold commodity exchange-traded fund. I also found the following: London Stock Exchange: Frequently Asked Questions about ETCs. The LSE ETC FAQ specifically mentions \"\"ETF Securities\"\" by name, and addresses questions such as how/where they are regulated, what happens to investments if \"\"ETF Securities\"\" were to go bankrupt, etc. I hope this helps, but please, do your own due diligence.\"",
"title": ""
},
{
"docid": "93836",
"text": "\"Because ETFs, unlike most other pooled investments, can be easily shorted, it is possible for institutional investors to take an arbitrage position that is long the underlying securities and short the ETF. The result is that in a well functioning market (where ETF prices are what they should be) these institutional investors would earn a risk-free profit equal to the fee amount. How much is this amount, though? ETFs exist in a very competitive market. Not only do they compete with each other, but with index and mutual funds and with the possibility of constructing one's own portfolio of the underlying. ETF investors are very cost-conscious. As a result, ETF fees just barely cover their costs. Typically, ETF providers do not even do their own trading. They issue new shares only in exchange for a bundle of the underlying securities, so they have almost no costs. In order for an institutional investor to make money with the arbitrage you describe, they would need to be able to carry it out for less than the fees earned by the ETF. Unlike the ETF provider, these investors face borrowing and other shorting costs and limitations. As a result it is not profitable for them to attempt this. Note that even if they had no costs, their maximum upside would be a few basis points per year. Lots of low-risk investments do better than that. I'd also like to address your question about what would happen if there was an ETF with exorbitant fees. Two things about your suggested outcome are incorrect. If short sellers bid the price down significantly, then the shares would be cheap relative to their stream of future dividends and investors would again buy them. In a well-functioning market, you can't bid the price of something that clearly is backed by valuable underlying assets down to near zero, as you suggest in your question. Notice that there are limitations to short selling. The more shares are short-sold, the more difficult it is to locate share to borrow for this purpose. At first brokers start charging additional fees. As borrowable shares become harder to find, they require that you obtain a \"\"locate,\"\" which takes time and costs money. Finally they will not allow you to short at all. Unlimited short selling is not possible. If there was an ETF that charged exorbitant fees, it would fail, but not because of short sellers. There is an even easier arbitrage strategy: Investors would buy the shares of the ETF (which would be cheaper than the value of the underlying because of the fees) and trade them back to the ETF provider in exchange for shares of the underlying. This would drain down the underlying asset pool until it was empty. In fact, it is this mechanism (the ability to trade ETF shares for shares of the underlying and vice versa) that keeps ETF prices fair (within a small tolerance) relative to the underlying indices.\"",
"title": ""
},
{
"docid": "402046",
"text": "Ending up with nothing is an unlikely situation unless you invest 100% in a company stock and the company goes under. In order to give you a good answer we need to see what options your employer gives for 401k investments. The best advice would be to take a list of all options that your employer allows and talk with a financial advisor. Here are a few options that you may or may not have as an option from an employer: Definitions from wikipedia: A target-date fund – also known as a lifecycle, dynamic-risk or age-based fund – is a collective investment scheme, usually a mutual fund, designed to provide a simple investment solution through a portfolio whose asset allocation mix becomes more conservative as the target date (usually retirement) approaches. An index fund or index tracker is a collective investment scheme (usually a mutual fund or exchange-traded fund) that aims to replicate the movements of an index of a specific financial market... An exchange-traded fund (ETF) is an investment fund traded on stock exchanges, much like stocks.[1] An ETF holds assets such as stocks, commodities, or bonds, and trades close to its net asset value over the course of the trading day. Most ETFs track an index, such as a stock index or bond index. ETFs may be attractive as investments because of their low costs, tax efficiency, and stock-like features. The capital stock (or stock) of an incorporated business constitutes the equity stake of its owners. Which one can you lose everything in? You can lose everything in stocks by the company going under. In Index funds the entire market that it follows would have to collapse. The chances are slim here since the index made up of several companies. The S&P 500 is made up of 500 leading companies publicly traded in the U.S. A Pacific-Europe index such as MSCI EAFE Index is made up of 907 companies. The chances of losing everything in an ETF are also slim. The ETF that follows the S&P 500 is made up of 500 companies. An Pacific-Europe ETF such as MSCI EAFE ETF is made up of 871 companies. Target date funds are also slim to lose everything. Target date funds are made up of several companies like indexes and etfs and also mix in bonds and other investments depending on your age. What would I recommend? I would recommend the Index funds and/or ETFs that have the lowest fee that make up the following strategy for your age: Why Not Target Date Funds or Stocks? Target date funds have high fees. Later in life when you are closer to retirement you may want to add bonds to your portfolio. At that time if this is the only option to add bonds then you can change your elections. Stocks are too risky for you with your current knowledge. If your company matches by buying their stock you may want to consider reallocating that stock at certain points to your Index funds or ETFs.",
"title": ""
},
{
"docid": "569565",
"text": "\"I thought the other answers had some good aspect but also some things that might not be completely correct, so I'll take a shot. As noted by others, there are three different types of entities in your question: The ETF SPY, the index SPX, and options contracts. First, let's deal with the options contracts. You can buy options on the ETF SPY or marked to the index SPX. Either way, options are about the price of the ETF / index at some future date, so the local min and max of the \"\"underlying\"\" symbol generally will not coincide with the min and max of the options. Of course, the closer the expiration date on the option, the more closely the option price tracks its underlying directly. Beyond the difference in how they are priced, the options market has different liquidity, and so it may not be able to track quick moves in the underlying. (Although there's a reasonably robust market for option on SPY and SPX specifically.) Second, let's ask what forces really make SPY and SPX move together as much as they do. It's one thing to say \"\"SPY is tied to SPX,\"\" but how? There are several answers to this, but I'll argue that the most important factor is that there's a notion of \"\"authorized participants\"\" who are players in the market who can \"\"create\"\" shares of SPY at will. They do this by accumulating stock in the constituent companies and turning them into the market maker. There's also the corresponding notion of \"\"redemption\"\" by which an authorized participant will turn in a share of SPY to get stock in the constituent companies. (See http://www.spdrsmobile.com/content/how-etfs-are-created-and-redeemed and http://www.etf.com/etf-education-center/7540-what-is-the-etf-creationredemption-mechanism.html) Meanwhile, SPX is just computed from the prices of the constituent companies, so it's got no market forces directly on it. It just reflects what the prices of the companies in the index are doing. (Of course those companies are subject to market forces.) Key point: Creation / redemption is the real driver for keeping the price aligned. If it gets too far out of line, then it creates an arbitrage opportunity for an authorized participant. If the price of SPY gets \"\"too high\"\" compared to SPX (and therefore the constituent stocks), an authorized participant can simultaneously sell short SPY shares and buy the constituent companies' stocks. They can then use the redemption process to close their position at no risk. And vice versa if SPY gets \"\"too low.\"\" Now that we understand why they move together, why don't they move together perfectly. To some extent information about fees, slight differences in composition between SPY and SPX over time, etc. do play. The bigger reasons are probably that (a) there are not a lot of authorized participants, (b) there are a relatively large number of companies represented in SPY, so there's some actual cost and risk involved in trying to quickly buy/sell the full set to capture the theoretical arbitrage that I described, and (c) redemption / creation units only come in pretty big blocks, which complicates the issues under point b. You asked about dividends, so let me comment briefly on that too. The dividend on SPY is (more or less) passing on the dividends from the constituent companies. (I think - not completely sure - that the market maker deducts its fees from this cash, so it's not a direct pass through.) But each company pays on its own schedule and SPY does not make a payment every time, so it's holding a corresponding amount of cash between its dividend payments. This is factored into the price through the creation / redemption process. I don't know how big of a factor it is though.\"",
"title": ""
},
{
"docid": "500486",
"text": "First, it's not always the case that ETFs have lower expenses than the equivalent mutual funds. For example, in the Vanguard family of funds the expense ratio for the ETF version is the same as it is for the Admiral share class in the mutual fund version. With that in mind, the main advantages of a mutual fund over an equivalent ETF are: From a long-term investor's point of view, the main disadvantage of mutual funds relative to ETFs is the minimum account sizes. Especially if the fund has multiple share classes (i.e., where better classes get lower expense ratios), you might have to have quite a lot of money invested in the fund in order to get the same expense ratio as the ETF. There are some other differences that matter to more active investors (e.g., intraday trading, options, etc.), but for a passive investor the ones above are the major ones. Apart from those mutual funds and ETFs are pretty similar. Personally, I prefer mutual funds because I'm at a point where the fund minimums aren't really an issue, and I don't want to deal with the more fiddly aspects of ETFs. For investors just starting out the lower minimum investment for an ETF is a big win, as long as you can get commission-free trades (which is what I've assumed above.)",
"title": ""
},
{
"docid": "407571",
"text": "\"Okay. An ETF is an \"\"Exchange Traded Fund\"\". It trades like a stock, on the stock market. Basically by buying one ETF, you can have ownership in the underlying companies that make up the ETF. So, if you buy QCLN, a green energy ETF, you own Tesla, First Solar Inc, SunPower Corporation, Vivint Solar, Advanced energy industries and a bunch of other companies that are involved in clean energy. It allows you to gain exposure to a sector without having to buy individual companies. There are ETFs for lots of different things. Technology ETFs, Healthcare ETFs, Consumer Staples ETFs, Utilities ETFs, etc. REITS are essentially the same thing, except they own real estate.\"",
"title": ""
},
{
"docid": "230997",
"text": "\"Back in the olden days, if you wanted to buy the S&P, you had to have a lot of money so you can buy the shares. Then somebody had the bright idea of making a fund that just buys the S&P, and then sells small pieces of it to investor without huge mountains of capital. Enter the ETFs. The guy running the ETF, of course, doesn't do it for free. He skims a little bit of money off the top. This is the \"\"fee\"\". The major S&P ETFs all have tiny fees, in the percents of a percent. If you're buying the index, you're probably looking at gains (or losses) to the tune of 5, 10, 20% - unless you're doing something really silly, you wouldn't even notice the fee. As often happens, when one guy starts doing something and making money, there will immediately be copycats. So now we have competing ETFs all providing the same service. You are technically a competitor as well, since you could compete with all these funds by just buying a basket of shares yourself, thereby running your own private fund for yourself. The reason this stuff even started was that people said, \"\"well why bother with mutual funds when they charge such huge fees and still don't beat the index anyway\"\", so the index ETFs are supposed to be a low cost alternative to mutual funds. Thus one thing ETFs compete on is fees: You can see how VOO has lower fees than SPY and IVV, in keeping with Vanguard's philosophy of minimal management (and management fees). Incidentally, if you buy the shares directly, you wouldn't charge yourself fees, but you would have to pay commissions on each stock and it would destroy you - another benefit of the ETFs. Moreover, these ETFs claim they track the index, but of course there is no real way to peg an asset to another. So they ensure tracking by keeping a carefully curated portfolio. Of course nobody is perfect, and there's tracking error. You can in theory compare the ETFs in this respect and buy the one with the least tracking error. However they all basically track very closely, again the error is fractions of the percent, if it is a legitimate concern in your books then you're not doing index investing right. The actual prices of each fund may vary, but the price hardly matters - the key metric is does it go up 20% when the index goes up 20%? And they all do. So what do you compare them on? Well, typically companies offer people perks to attract them to their own product. If you are a Fidelity customer, and you buy IVV, they will waive your commission if you hold it for a month. I believe Vanguard will also sell VOO for free. But for instance Fidelity will take commission from VOO trades and vice versa. So, this would be your main factor. Though, then again, you can just make an account on Robinhood and they're all commission free. A second factor is reliability of the operator. Frankly, I doubt any of these operators are at all untrustworthy, and you'd be buying your own broker's ETF anyway, and presumably you already went with the most trustworthy broker. Besides that, like I said, there's trivial matters like fees and tracking error, but you might as well just flip a coin. It doesn't really matter.\"",
"title": ""
},
{
"docid": "58690",
"text": "\"The problem with daily-rebalanced \"\"inverse\"\" or \"\"leveraged\"\" ETFs is that since they rebalance every day, you can lose money even if your guess as to the market's direction is correct. Quoting from FINRA'S guide as to why these are a bad idea: How can this apparent breakdown between longer term index returns and ETF returns happen? Here’s a hypothetical example: let’s say that on Day 1, an index starts with a value of 100 and a leveraged ETF that seeks to double the return of the index starts at $100. If the index drops by 10 points on Day 1, it has a 10 percent loss and a resulting value of 90. Assuming it achieved its stated objective, the leveraged ETF would therefore drop 20 percent on that day and have an ending value of $80. On Day 2, if the index rises 10 percent, the index value increases to 99. For the ETF, its value for Day 2 would rise by 20 percent, which means the ETF would have a value of $96. On both days, the leveraged ETF did exactly what it was supposed to do—it produced daily returns that were two times the daily index returns. But let’s look at the results over the 2 day period: the index lost 1 percent (it fell from 100 to 99) while the 2x leveraged ETF lost 4 percent (it fell from $100 to $96). That means that over the two day period, the ETF's negative returns were 4 times as much as the two-day return of the index instead of 2 times the return. That example is for \"\"just\"\" leveraging 2x in the same direction. Inverse funds have the same kind of issue. An example from Bogleheads Wiki page on these kinds of funds says that over 12/31/2007 to 12/31/2010, The funds do exactly what they say on any given day. But any losses get \"\"locked in\"\" each day. While normally a 50% loss needs a 100% gain to get back to a starting point, a fund like this needs more than a 100% gain to get back to its starting point. The result of these funds across multiple days doesn't match the index it's matching over those several days, and you won't make money over the long term. Do look at the further examples at the links I've referenced above, or do your own research into the performance of these funds during time periods both when the market is going up and going down. Also refer to these related and/or duplicate questions:\"",
"title": ""
},
{
"docid": "535581",
"text": "When you invest in an ETF or mutual fund, you're not investing in stocks or bonds. You're buying shares of a company that invests in stocks or bonds. This level of indirection is what makes it so bond funds do not 'mature.' Bonds inside of ETFs or mutual funds do have a maturity date. When they mature, the fund manager uses the principal value that is returned to purchase another bond that meets the investment objectives of the fund. So the fund never matures, since it is always investing in more bonds when the old ones mature. Unit investment trusts made of bonds do have a maturity date as well, since the portfolio does not change once the UIT is issued. As the individual bonds in the portfolio mature, the principle value is returned to investors. So the overall maturity date is effectively the maturity date of the last bond in the trust. All of the statements quoted above are accurate in explaining why there is no guarantee of a return of principle when investing in bond funds (ETF or open-ended mutual fund). The bonds they hold do mature, but are replaced within the fund as needed. The investor will never see it happen unless they watch the holdings reports filed by the funds. The only way to have an assurance of the return of principle is to invest in individual bonds, or in unit trusts made up of bonds.",
"title": ""
},
{
"docid": "244303",
"text": "\"I made an investing mistake many (eight?) years ago. Specifically, I invested a very large sum of money in a certain triple leveraged ETF (the asset has not yet been sold, but the value has decreased to maybe one 8th or 5th of the original amount). I thought the risk involved was the volatility--I didn't realize that due to the nature of the asset the value would be constantly decreasing towards zero! Anyhow, my question is what to do next? I would advise you to sell it ASAP. You didn't mention what ETF it is, but chances are you will continue to lose money. The complicating factor is that I have since moved out of the United States and am living abroad (i.e. Japan). I am permanent resident of my host country, I have a steady salary that is paid by a company incorporated in my host country, and pay taxes to the host government. I file a tax return to the U.S. Government each year, but all my income is excluded so I do not pay any taxes. In this way, I do not think that I can write anything off on my U.S. tax return. Also, I have absolutely no idea if I would be able to write off any losses on my Japanese tax return (I've entrusted all the family tax issues to my wife). Would this be possible? I can't answer this question but you seem to be looking for information on \"\"cross-border tax harvesting\"\". If Google doesn't yield useful results, I'd suggest you talk to an accountant who is familiar with the relevant tax codes. Are there any other available options (that would not involve having to tell my wife about the loss, which would be inevitable if I were to go the tax write-off route in Japan)? This is off topic but you should probably have an honest conversation with your wife regardless. If I continue to hold onto this asset the value will decrease lower and lower. Any suggestions as to what to do? See above: close your position ASAP For more information on the pitfalls of leveraged ETFs (FINRA) What happens if I hold longer than one trading day? While there may be trading and hedging strategies that justify holding these investments longer than a day, buy-and-hold investors with an intermediate or long-term time horizon should carefully consider whether these ETFs are appropriate for their portfolio. As discussed above, because leveraged and inverse ETFs reset each day, their performance can quickly diverge from the performance of the underlying index or benchmark. In other words, it is possible that you could suffer significant losses even if the long-term performance of the index showed a gain.\"",
"title": ""
},
{
"docid": "554015",
"text": "What account you put it in depends on why you have those different accounts. First, if you have them due to regulatory requirements, then you of course must follow said regulations. I doubt that's the case here. Otherwise, you might be splitting based on how they trade (ETFs trade as stocks) or you could be splitting based on how you build a portfolio out of them. When you build a non-speculative stock portfolio, you typically want to limit your holdings in a single stock to a fairly small portion of your portfolio (say, 3%) to limit your exposure to bad stuff happening to a single company. That doesn't apply nearly a much to mutual funds, especially index funds. ETFs are much more like mutual funds here. You can also, of course, create an ETF account and put them there. You also say you have a market index account, what is that used for?",
"title": ""
},
{
"docid": "536120",
"text": "Where are you planning on buying this ETF? I'm guessing it's directly through Vanguard? If so, that's likely your first reason - the majority of brokerage accounts charge a commission per trade for ETFs (and equities) but not for mutual funds. Another reason is that people who work in the financial industry (brokerages, mutual fund companies, etc) have to request permission for every trade before placing an order. This applies to equities and ETFs but does not apply to mutual funds. It's common for a request to be denied (if the brokerage has inside information due to other business lines they'll block trading, if a mutual fund company is trading the same security they'll block trading, etc) without an explanation. This can happen for months. For these folks it's typically easier to use mutual funds. So, if someone can open an account with Vanguard and doesn't work in the financial industry then I agree with your premise. The Vanguard Admiral shares have a much lower expense, typically very close to their ETFs. Source: worked for a brokerage and mutual fund company",
"title": ""
},
{
"docid": "119819",
"text": "\"You seem to be assuming that ETFs must all work like the more traditional closed-end funds, where the market price per share tends—based on supply and demand—to significantly deviate from the underlying net asset value per share. The assumption is simplistic. What are traditionally referred to as closed-end funds (CEFs), where unit creation and redemption are very tightly controlled, have been around for a long time, and yes, they do often trade at a premium or discount to NAV because the quantity is inflexible. Yet, what is generally meant when the label \"\"ETF\"\" is used (despite CEFs also being both \"\"exchange-traded\"\" and \"\"funds\"\") are those securities which are not just exchange-traded, and funds, but also typically have two specific characteristics: (a) that they are based on some published index, and (b) that a mechanism exists for shares to be created or redeemed by large market participants. These characteristics facilitate efficient pricing through arbitrage. Essentially, when large market participants notice the price of an ETF diverging from the value of the shares held by the fund, new units of the ETF can get created or redeemed in bulk. The divergence quickly narrows as these participants buy or sell ETF units to capture the difference. So, the persistent premium (sometimes dear) or discount (sometimes deep) one can easily witness in the CEF universe tend not to occur with the typical ETF. Much of the time, prices for ETFs will tend to be very close to their net asset value. However, it isn't always the case, so proceed with some caution anyway. Both CEF and ETF providers generally publish information about their funds online. You will want to find out what is the underlying Net Asset Value (NAV) per share, and then you can determine if the market price trades at a premium or a discount to NAV. Assuming little difference in an ETF's price vs. its NAV, the more interesting question to ask about an ETF then becomes whether the NAV itself is a bargain, or not. That means you'll need to be more concerned with what stocks are in the index the fund tracks, and whether those stocks are a bargain, or not, at their current prices. i.e. The ETF is a basket, so look at each thing in the basket. Of course, most people buy ETFs because they don't want to do this kind of analysis and are happy with market average returns. Even so, sector-based ETFs are often used by traders to buy (or sell) entire sectors that may be undervalued (or overvalued).\"",
"title": ""
},
{
"docid": "26939",
"text": "Don't start by investing in a few individual companies. This is risky. Want an example? I'm thinking of a big company, say $120 billion or so, a household name, and good consistent dividends to boot. They were doing fairly well, and were generally busy trying to convince people that they were looking to the future with new environmentally friendly technologies. Then... they went and spilled a bunch of oil into the Gulf of Mexico. Yes, it wasn't a pretty picture if BP was one of five companies in your portfolio that day. Things would look a lot better if they were one of 500 or 5000 companies, though. So. First, aim for diversification via mutual funds or ETFs. (I personally think you should probably start with the mutual funds: you avoid trading fees, for one thing. It's also easier to fit medium-sized dollar amounts into funds than into ETFs, even if you do get fee-free ETF trading. ETFs can get you better expense ratios, but the less money you have invested the less important that is.) Once you have a decent-sized portfolio - tens of thousands of dollars or so - then you can begin to consider holding stocks of individual companies. Take note of fees, including trading fees / commissions. If you buy $2000 worth of stock and pay a $20 commission you're already down 1%. If you're holding a mutual fund or ETF, look at the expense ratio. The annualized real return on the stock market is about 4%. (A real return is after adjusting for inflation.) If your fee is 1%, that's about a quarter of your earnings, which is huge. And while it's easy for a mutual fund to outperform the market by 1% from time to time, it's really really hard to do it consistently. Once you're looking at individual companies, you should do a lot of obnoxious boring stupid research and don't just buy the stock on the strength of its brand name. You'll be interested in a couple of metrics. The main one is probably the P/E ratio (price/earnings). If you take the inverse of this, you'll get the rate at which your investment is making you money (e.g. a P/E of 20 is 5%, a P/E of 10 is 10%). All else being equal, a lower P/E is a good thing: it means that you're buying the company's income really cheap. However, all else is seldom equal: if a stock is going for really cheap, it's usually because investors don't think that it's got much of a future. Earnings are not always consistent. There are a lot of other measures, like beta (correlation to the market overall: riskier volatile stocks have higher numbers), gross margins, price to unleveraged free cash flow, and stuff like that. Again, do the boring research, otherwise you're just playing games with your money.",
"title": ""
},
{
"docid": "24742",
"text": "Right now, the unrealized appreciation of Vanguard Tax-Managed Small-Cap Fund Admiral Shares is 28.4% of NAV. As long as the fund delivers decent returns over the long term, is there anything stopping this amount from ballooning to, say, 90% fifty years hence? I'd have a heck of a time imagining how this grows to that high a number realistically. The inflows and outflows of the fund are a bigger question along with what kinds of changes are there to capital gains that may make the fund try to hold onto the stocks longer and minimize the tax burden. If this happens, won't new investors be scared away by the prospect of owing taxes on these gains? For example, a financial crisis or a superior new investment technology could lead investors to dump their shares of tax-managed index funds, triggering enormous capital-gains distributions. And if new investors are scared away, won't the fund be forced to sell its assets to cover redemptions (even if there is no disruptive event), leading to larger capital-gains distributions than in the past? Possibly but you have more than a few assumptions in this to my mind that I wonder how well are you estimating the probability of this happening. Finally, do ETFs avoid this problem (assuming it is a problem)? Yes, ETFs have creation and redemption units that allow for in-kind transactions and thus there isn't a selling of the stock. However, if one wants to pull out various unlikely scenarios then there is the potential of the market being shut down for an extended period of time that would prevent one from selling shares of the ETF that may or may not be as applicable as open-end fund shares. I would however suggest researching if there are hybrid funds that mix open-end fund shares with ETF shares which could be an alternative here.",
"title": ""
},
{
"docid": "295993",
"text": "ETFs are legally required to publicly disclose their positions at every point in time. The reason for this is that for an ETF to issue shares of ETF they do NOT take cash in exchange but underlying securities - this is called a creation unit. So people need to know which shares to deliver to the fund to get a share of ETF in exchange. This is never done by retail clients, however, but by nominated market makers. Retail persons will normally trade shares only in the secondary market (ie. on a stock exchange), which does not require new shares of the ETF to be issued. However, they do not normally make it easy to find this information in a digestible way, and each ETF does it their own way. So typically services that offer this information are payable (as somebody has to scrape the information from a variety of sources or incentivise ETF providers to send it to them). If you have access to a Bloomberg terminal, this information is available from there. Otherwise there are paid for services that offer it. Searching on Google for ETF constituent data, I found two companies that offer it: See if you can find what you need there. Good luck. (etfdb even has a stock exposure tool freely available that allows you to see which ETFs have large exposure to a stock of your choosing, see here: http://etfdb.com/tool/etf-stock-exposure-tool/). Since this data is in a table format you could easily download it automatically using table parsing tools for your chosen programming language. PS: Don't bother with underlying index constituents, they are NOT required to be made public and index providers will normally charge handsomely for this so normally only institutional investors will have this information.",
"title": ""
},
{
"docid": "367960",
"text": "\"I think you are asking about actively managed funds vs. indexes and possibly also vs. diversified funds like target date funds. This is also related to the question of mutual fund vs. ETF. First, a fund can be either actively managed or it can attempt to track an index. An actively managed fund has a fund manager who tries to find the best stocks to invest in within some constraints, like \"\"this fund invests in large cap US companies\"\". An index fund tries to match as closely as possible the performance of an index like the S&P 500. A fund may also try to offer a portfolio that is suitable for someone to put their entire account into. For example, a target date fund is a fund that may invest in a mix of stocks, bonds and foreign stock in a proportion that would be appropriate to someone expecting to retire in a certain year. These are not what people tend to think of as the canonical examples of mutual funds, even though they share the same legal structure and investment mechanisms. Secondly, a fund can either be a traditional mutual fund or it can be an exchange traded fund (ETF). To invest in a traditional mutual fund, you send money to the fund, and they give you a number of shares equal to what that money would have bought of the net asset value (NAV) of the fund at the end of trading on the day they receive your deposit, possibly minus a sales charge. To invest in an ETF, you buy shares of the ETF on the stock market like any other stock. Under the covers, an ETF does have something similar to the mechanism of depositing money to get shares, but only big traders can use that, and it's not used for investing, but only for people who are making a market in the stock (if lots of people are buying VTI, Big Dealer Co will get 100,000 shares from Vanguard so that they can sell them on the market the next day). Historically and traditionally, ETFs are associated with an indexing strategy, while if not specifically mentioned, people assume that traditional mutual funds are actively managed. Many ETFs, notably all the Vanguard ETFs, are actually just a different way to hold the same underlying fund. The best way to understand this is to read the prospectus for a mutual fund and an ETF. It's all there in reasonably plain English.\"",
"title": ""
},
{
"docid": "352557",
"text": "Use a currency ETF. there are many. Specific to your question there is WisdomTree Dreyfus Brazilian Real Fund (BZF) I don't happen to find a currency ETF for Thailand, so the closest you could come to a Thai currency fund would be something that's an Index fund ETF that is based on an index in the Thai Market such as: MSCI Thailand Investable Market Index Fund Because that fund is investing in an index of stocks that trade on the Thai market, you are in effect investing in something denominated in Baht. This is spelled out in the prospectus where it discusses 'currency risk'. The problem is that you are however not investing in just the currency, but rather a broad index of stocks denominated in that currency. Still to the extent the market holds fairly steady, you get much the same effect of investing in just the currency. to the extent the market is moving, you get the net effect of what the thai market does, plus how the bhat trades relative to the dollar.",
"title": ""
},
{
"docid": "343594",
"text": "\"Remember that in most news outlets journalists do not get to pick the titles of their articles. That's up to the editor. So even though the article was primarily about ETFs, the reporter made the mistake of including some tangential references to mutual funds. The editor then saw that the article talked about ETFs and mutual funds and -- knowing even less about the subject matter than the reporter, but recognizing that more readers' eyeballs would be attracted to a headline about mutual funds than to a headline about ETFs -- went with the \"\"shocking\"\" headline about the former. In any case, as you already pointed out, ETFs need to know their value throughout the day, as do the investors in that ETF. Even momentary outages of price sources can be disastrous. Although mutual funds do not generally make transactions throughout the day, and fund investors are not typically interested in the fund's NAV more than once per day, the fund managers don't just sit around all day doing nothing and then press a couple buttons before the market closes. They do watch their NAV very closely during the day and think very carefully about which buttons to press at the end of the day. If their source of stock price data goes offline, then they're impacted almost as severely as -- if less visibly than -- an ETF. Asking Yahoo for prices seems straightforward, but (1) you get what you pay for, and (2) these fund companies are built on massive automated infrastructures that expect to receive their data from a certain source in a certain way at a certain time. (And they pay a lot of money in order to be able to expect that.) It would be quite difficult to just feed in manual data, although in the end I suspect some of these companies did just that. Either they fell back to a secondary data supplier, or they manually constructed datasets for their programs to consume.\"",
"title": ""
},
{
"docid": "451884",
"text": "\"AFAIK, It's also possible that the ETF company is paying Ameritrade for every trade you make. Even if your brokerage doesn't make you pay a fee to trade ETFs, the company that created and runs the ETF is still making money when you purchase and use their ETFs. See \"\"What motivates each player?\"\" at Yahoo Finance.\"",
"title": ""
},
{
"docid": "11032",
"text": "\"Let me provide a general answer, that might be helpful to others, without addressing those specific stocks. Dividends are simply corporate payouts made to the shareholders of the company. A company often decides to pay dividends because they have excess cash on hand and choose to return it to shareholders by quarterly payouts instead of stock buy backs or using the money to invest in new projects. I'm not exactly sure what you mean by \"\"dividend yield traps.\"\" If a company has declared an dividend for the upcoming quarter they will almost always pay. There are exceptions, like what happened with BP, but these exceptions are rare. Just because a company promises to pay a dividend in the approaching quarter does not mean that it will continue to pay a dividend in the future. If the company continues to pay a dividend in the future, it may be at a (significantly) different amount. Some companies are structured where nearly all of there corporate profits flow through to shareholders via dividends. These companies may have \"\"unusually\"\" high dividends, but this is simply a result of the corporate structure. Let me provide a quick example: Certain ETFs that track bonds pay a dividend as a way to pass through interest payments from the underlying bonds back to the shareholder of the ETF. There is no company that will continue to pay their dividend at the present rate with 100% certainty. Even large companies like General Electric slashed its dividend during the most recent financial crisis. So, to evaluate whether a company will keep paying a dividend you should look at the following: Update: In regards to one the first stock you mentioned, this sentence from the companies of Yahoo! finance explains the \"\"unusually\"\" dividend: The company has elected to be treated as a REIT for federal income tax purposes and would not be subject to income tax, if it distributes at least 90% of its REIT taxable income to its share holders.\"",
"title": ""
},
{
"docid": "304023",
"text": "\"ETF Creation and Redemption Process notes the process: While ETF trading occurs on an exchange like stocks, the process by which their shares are created is significantly different. Unless a company decides to issue more shares, the supply of shares of an individual stock trading in the marketplace is finite. When demand increases for shares of an ETF, however, Authorized Participants (APs) have the ability to create additional shares on demand. Through an \"\"in kind\"\" transfer mechanism, APs create ETF units in the primary market by delivering a basket of securities to the fund equal to the current holdings of the ETF. In return, they receive a large block of ETF shares (typically 50,000), which are then available for trading in the secondary market. This ETF creation and redemption process helps keep ETF supply and demand in continual balance and provides a \"\"hidden\"\" layer of liquidity not evident by looking at trading volumes alone. This process also works in reverse. If an investor wants to sell a large block of shares of an ETF, even if there seems to be limited liquidity in the secondary market, APs can readily redeem a block of ETF shares by gathering enough shares of the ETF to form a creation unit and then exchanging the creation unit for the underlying securities. Thus, the in-kind swap to the underlying securities is only done by APs so the outflow would be these individuals taking a large block of the ETF and swapping it for the underlying securities. The APs would be taking advantage of the difference between what the ETF's trading value and the value of the underlying securities.\"",
"title": ""
}
] |
10672
|
How can I find/compare custodians for my HSA in the United States?
|
[
{
"docid": "277607",
"text": "In general, things to look for are: Things to look out for: I'd recommend two places: I'd recommend reading up on HSA's in this related question here.",
"title": ""
},
{
"docid": "476923",
"text": "\"The account I have found that works best as a HSA is Alliant Credit Union. They have fee-free HSA (no fees for almost all types of transactions or monthly fees) and a fairly decent online banking website. I've been with them for about 5 years now without trouble. FYI - They are a credit union not a bank so you do have to make a small $10 donation to one of their charities to become \"\"eligible\"\" for opening the account.\"",
"title": ""
}
] |
[
{
"docid": "187196",
"text": "I have a little experience with this. My home state of Wisconsin was on this list until 2011. The thing to remember is that these states simply do not recognize the HSA. What this means is that there are no state income tax advantages to the account, and no state tax penalties, either. Here are the implications: When you invest in a taxable account, your broker in many cases keeps track of cost basis for you. However, when you invest inside an HSA, your HSA custodian will generally not keep track of any of this, because it is not normally needed. Therefore, you need to keep track of any cost basis yourself, and when you sell, calculate the capital gain or loss on your state return. In my opinion, the HSA is a good deal even if your state does not recognize it. The tax-free savings/investing is a great deal, even if only on your Federal taxes. The state return will be a little more complicated, but the savings you get on your federal return are worth it. In my situation, our family spends the money in the HSA on medical expenses fast enough that we don't invest it in anything other than an interest-bearing savings account. Therefore, we didn't have to worry about capital gains inside our HSA, and only had to add contributions and earnings to our state income. I am very glad that our state now recognizes the HSA.",
"title": ""
},
{
"docid": "486443",
"text": "My answer is with respect to the United States. I have no idea about India's regulatory environment. You are opening yourself up to massive liabilities and problems if you deposit their money in your account. I managed investment accounts as a private investment advisor for years (those with less than 15 clients were not required to register) until Dodd-Frank changed the rules. Thus you would have to register as an advisor, probably needing to take the series 65 exam (or qualifying some other way, e.g. getting your CFP/CFA/etc...). I used a discount broker/dealer (Scottrade) as the custodian. Here's how it works: Each client's account was their own account, and I had a master account that allowed me to bill their accounts and manage them. They signed paperwork making me the advisor on their account. I had very little accounting to handle (aside from tracking basis for taxed accounts). If you take custody of the money, you'll have regulatory obligations. There are always lots of stories in the financial advisor trade publications about advisors who go to jail for screwing their clients. The most common factor: they took custody of the assets. I understand why you want a single account - you want to ensure that each client gets the same results, right? Does each client want the same results? Certainly the tax situation for each is different, yes? Perhaps one has gains and wants to take losses in one year, and the other doesn't. If their accounts are managed separately, one can take losses while the other realizes gains to offset other losses. Financial advisors offer these kinds of accounts as Separately Managed Accounts (SMAs). The advisors on these kinds of accounts are mutual funds managers, and they try to match a target portfolio, but they can do things like realize gains or losses for clients if their tax situation would prefer it. You certainly can't let them put retirement accounts into your single account unless the IRS has you on their list of acceptable custodians. I suggest that you familiarize yourself thoroughly with the regulatory environment that you want to operate under. Then, after examining the pros and cons, you should decide which route you want to take. I think the most direct and feasible route is to pass the Series 65, register as an investment advisor, and find a custodian who will let you manage the assets as the advisor on the account. Real estate is another matter, you should talk to an attorney, not some random guy on the internet (even if he has an MBA and a BS in Real Estate, which I do). This is very much a state law thing.",
"title": ""
},
{
"docid": "1134",
"text": "The HSA money is yours to keep. You can't add new money into the account and get a tax deduction for the new money, but you can spend the old money on medical expenses. First log into the website for the HSA and see if you have money left. This can be important because if there is still money left they might be charging you a monthly fee. You should have gotten a letter from the old company or the administrator when you left the High deductible insurance plan. This would have told you your options regarding the spending or transferring of old funds. HSA related numbers would have appeared on your W2, and you should have a 1099-SA from the administrator. It is likely that there is a copy of the 1099 on the administrators website. The numbers you enter on the tax forms depends on how much you contributed from your paycheck, how much your company contributed, and how much you sent (if any) from other sources besides payroll deduction. You will also have to know how much money was withdrawn from the HSA and how much was used for medical purposes. The last month rule is for those people who start in the middle of the year. If you start partway through the year you are allowed to make the maximum contribution if you still have it at the end of the year, and you expect to keep it. The Last Month Rule The Last Month Rule states that if you are covered by an HSA eligible health plan on the first day of the last month of a given year, you are considered an eligible individual for the entire year. In turn, you can then contribute to the HSA for that full year. If you are covered by an HDHP on Dec 1st of a given year, you may contribute the maximum for that year. For example, you could begin coverage and open up my HSA in November of a given year. Come December 1st, you are covered and per the Last Month Rule, considered an eligible employee for that full year. That allows you to contribute up to that year’s contribution limit, even waiting a few months to make a prior year contribution if you like. Back up the truck and load up the HSA! However, there is a catch. The Testing Period The Testing Period states if you use the Last Month Rule, you must remain an eligible individual (covered by HDHP) for the following 12 months. If you fail to remain an eligible individual (change insurance plans, lose insurance plan, receive other health coverage) any “extra” contributions you made as a result of the Last Month Rule will be taxed and penalized. If you contribute per the Last Month Rule and end your HDHP insurance within 1 year, you will have to pay tax on any excess contributions you were allowed to make and pay a 10% penalty. In this case, “excess” contributions are determined by the contribution limit / 12 months, compared to your time eligible.",
"title": ""
},
{
"docid": "591069",
"text": "Much of this is incorrect. Aetna owns Payflex for starters, and it's your EMPLOYER who decides which banks and brokers to offer, not Payflex. An HSA is a checking account with an investment account option after a minimum balance is met. A majority of U.S. employers only OFFER an HSA option but don't contribute a penny, so you're lucky you get anything. The easy solution is just keep the money that is sent to your HSA checking account in your checking account, and once a year roll it over into a different bank's HSA. The vast majority of banks offer HSAs that have no ties to a particular broker (i.e. Citibank, PNC, Chase). I have all my HSA funds in HSA Bank which is online but services lots of employers. Not true that most payroll deductions or employer contributions go to a single HSA custodian (bank). They might offer a single bank that either contracts with an investment provider or lets you invest anywhere. But most employers making contributions are large or mid-market employers offering multiple banks, and that trend is growing fast because of defined contribution, private exchanges and vendor product redesigns. Basically, nobody likes having a second bank account for their HSA when their home bank offers one.",
"title": ""
},
{
"docid": "104134",
"text": "\"You can move money from a 403b to a 401k plan, but the question you should ask yourself is whether it is a wise decision. Unless there are specific reasons for wanting to invest in your new employer's 401k (e.g. you can buy your employer's stock at discounted rates within the 401k, and this is a good investment according to your friends, neighbors, and brothers-in-law), you would be much better off moving the 403b money into an IRA, where you have many more choices for investment and usually can manage to find investments with lower investment costs (e.g. mutual fund fees) than in a typical employer's 401k plan. On the other hand, 401k assets are better protected than IRA assets in case you are sued and a court finds you to be liable for damages; the plaintiff cannot come after the 401k assets if you cannot pay. To answer the question of \"\"how?\"\", you need to talk to the HR people at your current employer to make sure that they are willing to accept a roll-over from another tax-deferred plan (not all plans are agreeable to do this) and get any paperwork from them, especially making sure that you find out where the check is to be sent, and to whom it should be payable. Then, talk to your previous employer's HR people and tell them that you want to roll over your 403b money into the 401k plan of your new employer, fill out the paperwork, make sure they know to whom to cut the check to, and where it is to be sent etc. In my personal experience, I was sent the check payable to the custodian of my new (IRA) account, and I had to send it on to the custodian; my 403b people refused to send the check directly to the new custodian. The following January, you will receive a 1099-R form from your 403b plan showing the amount transferred to the new custodian, with hopefully the correct code letter indicating that the money was rolled over into another tax-deferred account.\"",
"title": ""
},
{
"docid": "454610",
"text": "\"I wonder if ETF's are further removed from the actual underlying holdings or assets giving value to the fund, as compared to regular mutual funds. Not exactly removed. But slightly different. Whenever a Fund want to launch an ETF, it would buy the underlying shares; create units. Lets say it purchased 10 of A, 20 of B and 25 of C. And created 100 units for price x. As part of listing, the ETF company will keep the purchased shares of A,B,C with a custodian. Only then it is allowed to sell the 100 units into the market. Once created, units are bought or sold like regular stock. In case the demand is huge, more units are created and the underlying shares kept with custodian. So, for instance, would VTI and Total Stock Market Index Admiral Shares be equally anchored to the underlying shares of the companies within the index? Yes they are. Are they both connected? Yes to an extent. The way Vanguard is managing this is given a Index [Investment Objective]; it is further splitting the common set of assets into different class. Read more at Share Class. The Portfolio & Management gives out the assets per share class. So Vanguard Total Stock Market Index is a common pool that has VTI ETF, Admiral and Investor Share and possibly Institutional share. Is VTI more of a \"\"derivative\"\"? No it is not a derivative. It is a Mutual Fund.\"",
"title": ""
},
{
"docid": "82874",
"text": "If you know you will have a big bill, like braces. and you fully expect to hit the deductible then it can make sense. The deductible can trip some people up, because if they put too much into the limited purpose FSA and don't hit the deductible for the regular insurance policy, they can't get to all the money in the FSA. Because you have the ability to spend the potential money in the FSA before all the money has been contributed, it can allow you to make that payment for the braces in January. I did this the first year we had the HSA. I knew I needed to pay a dental bill early in the year. But the HSA would only have a few hundred dollars at that time, so I used the limited purpose FSA to be able to make that payment. This could also work if you spent a lot of money in the previous year. Because you have the ability to adjust how much money goes into the HSA each each pay period, this idea does keep the option open to fully fund the HSA if your finances improve. Regarding the deductible. The law limits what you can use the limited purpose FSA for: dental and vision only. There is an exception. If you hit the deductible for the high deductible insurance policy, then you can use the funds in the limited purpose FSA for ANY medical reason. When I did this a few years ago, I needed to send extensive paperwork to the company holding the funds before they would release the funds for dental. Once I sent them proof that I had met the deductible, then any medical expense after that date could use the FSA with minimal paperwork. If you fully fund the FSA beyond the cost of the braces, and then have a light year medical expense wise, you might not be able to spend all money in the FSA by the deadline. Regarding state taxes. I saw no difference in my states (Virginia) treatment of the funds. The state taxable income number was exactly the same as the federal taxable income number. It did not treat the money in the FSA differently than the money in the HSA.",
"title": ""
},
{
"docid": "402982",
"text": "Here are the advantages to the HDHP/HSA option over the PPO option, some of which you've already mentioned: Lower premiums, saving $240 annually. Your employer is contributing $1500 to your HSA. As you mentioned, this covers your deductible if you need it, and if you don't, the $1500 is yours to keep inside your HSA. The ability to contribute more to your HSA. You will be able to contribute additional funds to your HSA and take a tax deduction. Besides the medical expenses applied to your deductible, HSA funds can be spent on medical expenses that are not covered by your insurance, such as dental, vision, chiropractic, etc. Anything left in your HSA at age 65 can be withdrawn just like with a traditional IRA, with tax due (but no penalty) on anything not spent on medical expenses. With the information that you've provided about your two options, I can't think of any scenario where you'd be better off with the PPO. However, you definitely want to look at all the rest of the details to ensure that it is indeed the same coverage between the two options. If you find differences, I wrote an answer on another question that walks you through comparing insurance options under different scenarios.",
"title": ""
},
{
"docid": "349706",
"text": "\"The presenter suggested we keep records of our claims for 10+ years in paper form. This seemed to be overkill. It would be overkill if you're taking distributions regularly and you have enough valid (and otherwise unreimbursed) medical receipts each year to correspond to your distributions. However, if you are pumping money into the HSA without regular distributions, then you may need to keep receipts for a long time, possibly since the beginning of your HSA. For example: If the IRS was to audit my HSA deductions would the Aetna online claims be adequate? It's better than nothing, but it is not ideal. You need to provide proof of what you actually paid, not just what was billed. (How would the IRS know if you actually paid the bill?) So, the bill and receipt together would be preferred. Also, there are many eligible expenses for HSA that would not be covered by your health insurance and would not appear in your Aetna statements (dental work for example). Personally I have an excel spreadsheet with every eligible expense listed, every contribution and distribution I make, and a box of receipts since I opened the HSA account. Should I also archive screenshots of these claims digitally somewhere? If you have the time and diligence to do it, then it wouldn't hurt. I personally am only one house fire away from having to make a lot of phone calls if I wanted to re-build my receipts folder from scratch. I actually have \"\"scan my HSA receipts\"\" on my todo list (where's it been for years as a pretty low priority). Lastly it makes sense to spend the money in my HSA on anything eligible because you can never roll it over into a retirement account, its shaky if another person (spouse) could get reimbursed for eligible medical expenses if you die, and if you lose your receipts you may not be able to spend all of the HSA money tax free. Is this an accurate assessment or is there a reason why I should not touch the HSA money at all and wait to reimburse my eligible expenses. First off, if you are married the HSA can be transferred to your spouse. But in general, it really depends on what you would do with the money if you distributed it right away. If you need the money to pay debts, bills, etc, then it might make sense to take it, but if it would be extra money that you would invest somewhere, then you should leave it in the HSA because it grows tax free while it's in there and (probably) wouldn't if you take it out. The caveat though is that you need to find an HSA administrator that offers your preferred investment choices. As for your worry that you might lose your receipts, well, that's a valid point- but I wouldn't drive my decision based on that- I would archive them digitally to remove that concern completely. ...Should I reimburse myself from ... the HSA funds if I am not hitting the 401k limit yet? It depends. If it's a Roth 401k, all other things being equal, (you are able to choose the same investments with your HSA as you can choose in your 401K, and the costs are the same), then you are better off leaving the money in your HSA rather than pulling it out and putting it into the Roth 401k. The reason is that there is no tax difference, and once you put it into the 401K you (probably) can't touch it (for free) until you retire. With the HSA, if you could have taken a distribution but chose not to, then you can take that amount of money out anytime you want to without any consequences, just like your normal checking account. However, if you have a traditional 401k, and if taking HSA distributions would increase your cash flow such that you could afford to contribute more to the 401k, then this would lower your tax burden that year by reducing your taxable income.\"",
"title": ""
},
{
"docid": "155847",
"text": "\"First, your employee needs to work out his contribution limit for the year. Because he was eligible for a few months, his limit will be prorated. See this post for details on how to calculate the prorated limit. Once he determines his contribution limit, you'll know how much needs to be taken out. You (or he) can do an excess contribution withdrawal to remove the extra contribution without penalty. See this post for more details. If he has already spent some or all of the extra contribution, talk to the HSA custodian. They may be able to reclassify some of his distributions as excess contribution withdrawals. You won't get the money back, but it will avoid the penalty. Your employee would then need to add the extra as \"\"other income\"\" on his tax return so he can pay tax on it. You have until April 15 to remove the excess HSA contributions. If you are unable to do it by then, the penalty to your employee is 6% (Source: Pub 969) on the excess that is not removed, in addition to the income tax.\"",
"title": ""
},
{
"docid": "166627",
"text": "That is an opinion. I don't think so. Here are some differences: If you use credit responsibly and take the time to make sure the reporting agencies are being accurate, a good report can benefit you. So that isn't like a criminal record. What is also important to know is that in the United States, a credit report is about you, not for you. You are the product being sold. This is, in my opinion, and unfortunate situation but it is what it is. You will more than likely benefit for keeping a good report, even if you never use credit. There are many credit scores that can be calculated from your report; the score is just a number used to compare and evaluate you on a common set of criteria. If you think about it, that doesn't make sense. The score is a reflection of how you use credit. Having and using credit is a commitment. Your are committing to the lender that you will repay them as agreed. Your choice is who you decide to make agreements with. I personally find the business practices of my local credit union to be more palatable than the business practices of the national bank I was with. I chose to use credit provided by the credit union rather than by the bank. I am careful about where I take auto loans from, and to what extent I can control it, where I take home loans from. Since it is absolutely a commitment, you are personally responsible for making sure that you like who you are making commitments with.",
"title": ""
},
{
"docid": "174784",
"text": "CrimsonX did a great job highlighting the primary pros and cons of HSAs, so I won't go into detail there. However, I did want to point out another pro - HSAs are (or can be) easy to manage. You said: Is this a better way to approach health care costs instead of itemizing health care expenses on yearly federal taxes? I'm not sure which company you are looking at establishing your HSA with, but with mine I have a debit card that I use when paying for medical care and then at the end of the year I get a 1099-SA that provides the amount of money spent on qualified purchases that calendar year. Yes, there are a few extra boxes I need to fill in for my 1040 come tax time, but I don't need to itemize my healthcare costs over the year. It really is pretty simple and straightforward. Also, one con that is worth noting is that you become much more sensitive to healthcare costs due to the high deductible healthcare plan an HSA requires. For example, in all the years we've had an HSA we've not yet met our deductible, which means we pay out of pocket for any non-routine doctor visits. (The health insurer pays 100% of routine visits, like my wife's annual, well-baby check ups for the little one, and so on.) So, when you're feeling really sick and think a doctor's visit would be warranted, you have to make a decision: After being faced with this decision a time or two you will start to envy those who have just a $20 copay! Of course, that's just an emotional con. Each year I run the numbers on how much we spent per year on out of pocket plus premiums and compare it to what it would cost in premiums for an HMO-type plan, and the HSA plan always comes ahead. (In part because we are a pretty healthy family and I work for myself so do not get to enjoy group discount rates.) But I thought it worth mentioning because there are certainly times when I know I need to see a doctor or specialist and I cringe because I know I am going to be slapped with a big bill in the not too distant future!",
"title": ""
},
{
"docid": "414429",
"text": "\"Uniform Transfer to Minors Act (UTMA) and Uniform Gift to Minors Act (UGMA) accounts in the United States are accounts that belong to your child, but you can deposit money into. When the child attains his/her majority, the money becomes theirs to spend however they wish. Prior to attaining their majority, a custodian must sign off on withdrawals. Now, they are not foolproof; legally, you can withdraw money if it is spent on the child's behalf, so that can be gamed. What you can do to protect against that is to make another person the custodian (or, perhaps make them joint custodians with yourself, requiring both signatures for withdrawals). UTMA/UGMA accounts do not have to be bank savings accounts; for example, both of my children have accounts at Vanguard which are effectively their college savings accounts. They're invested in various ETFs and similar kinds of investments; you're welcome to choose from a wide variety of options depending on risk tolerance. Typically these accounts have relatively small fees, particularly if you have a reasonable minimum balance (I think USD$10k is a common minimum for avoiding larger fees). If you are looking for something even more secure than a UGMA or UTMA account, you can set up a trust. These have several major differences over the UGMA/UTMA accounts: Some of course consider the second point an advantage, some a disadvantage - we (and Grandma) prefer to let our children make their own choices re: college, while others may not prefer that. Also worth noting as a difference - and concern to think about - in these two. A UGMA or UTMA account that generates income may have taxable events - interest or dividend income. If that's over a relatively low threshhold, about $1050 this year, those earnings will be taxed (on the child's own tax return). If it's over $2100 (this year), those earnings will be taxed at the parents' tax rate (\"\"kiddie tax\"\"). Trusts are slightly different; trusts themselves are taxed, and have their own tax returns. If you do set one of those up, the lawyer who helps you do so should inform you of the tax implications and either hook you up with an accountant or point you to resources to handle the taxes yourself.\"",
"title": ""
},
{
"docid": "257771",
"text": "There are some points not covered in the other answers that I feel are important to address: In order to be eligible to contribute to an HSA, you must be enrolled in a High Deductible Health insurance Plan (HDHP). In general, I think this is a great idea for most people (who are responsible enough to save up for medical expenses), but for a small portion it may cost more money to enroll in this type of plan, due to high recurring medical costs. You should always weigh the costs of the related insurance plans against the benefit of an HSA. Note that once you open an account and contribute, you can use the funds at any point after that. The eligibility described here is only regarding making new contributions to the account. This may no longer be true, but when I first started using an HSA several years back, I noticed that the fees and costs administered by the providers were higher than I’d come to expect from, say, my IRA administrator. At least, this was true for the accounts I found – perhaps I missed a better option. Furthermore, there was a much smaller selection of investment options available in those HSAs than in other brokerage accounts. If you are not maxing out retirement already, it’s worth comparing fees and historical returns versus those accounts rather than assuming that the tax benefits will make the HSA a better deal. In my book, if it passes these two checks, then the HSA is a tremendous deal that is highly under-utilized.",
"title": ""
},
{
"docid": "179133",
"text": "Do You Consult Or Just Do The Job?….. For as long as I can remember I have always sought out information, knowledge, facts, figures. One of my ex-bosses once said to me that I could always be relied on to find untapped resources & deliver. This was when I was in my early 20′s & its a skill that I feel is vital for the success of any business. My second job, when I was 19yrs old was in an Advertising / PR company - I was the Secretary. Part of my remit was credit control & book-keeping, for some reason I was always naturally interested in sales units sold & values – then see how the total sales compared to the previous month / year. Little did I know, this was a good skill for Profit & Loss sheets in years to come!",
"title": ""
},
{
"docid": "397749",
"text": "There could be a number of reasons for a rent increase. The only information I can offer is how I calculate what rent I will charge. The minimum I would ever charge per unit (Mortgage payment + Water) / Number of units This number is the minimum because it's what I need to keep afloat. Keep in mind these are ballpark numbers The target rent ((Mortgage payment + Water) / Number of units)*1.60 I mark up the price 60% for a few reasons. First, the building needs a repair budget. That money has to come from somewhere. Second, I want to put away for my next acquisition and third I want to make a profit. These get me close to my rental price but ultimately it depends on your location and the comparables in the area. If my target rent is 600 a month but the neighbors are getting 700-800 for the same exact unit I might ask more. It also depends on the types of units. Some of my buildings, all of the units are identical. Other buildings half of the units are bigger than the other half so clearly I wouldn't charge a equal amount for them. Ultimately you have to remember we're not in the game to lose money. I know what my renters are going to pay before I even put an offer in on a building because that's how I stay in business. It might go up over the years but it will always outpace my expenses for that property.",
"title": ""
},
{
"docid": "387547",
"text": "It is my understanding that the money in the HSA is yours to keep forever, even if you leave the country. When you leave the country and no longer have an HSA-eligible High Deductible Health Plan, you will no longer be able to contribute new money to your HSA. However, you can still spend the money on eligible medical expenses, even if these expenses are outside the U.S. However, there are a few caveats: The HSA money will remain in a U.S. HSA bank account. You won't be able to transfer the entire account to a new account in your home country without paying taxes and penalty. Therefore, you need to have a mechanism for accessing and transferring the money from abroad, so that you can reimburse yourself as you have medical expenses, until the HSA account is empty. Even after you leave the U.S., as long as you have the HSA in place, you will need to file a U.S. tax return (form 1040NR) in any year that you have an HSA distribution. If you decide to take the money out without medical expenses, you will need to pay income tax on the money plus a 20% penalty. See How do I withdraw all money from my HSA account as a non-resident? for more information.",
"title": ""
},
{
"docid": "484424",
"text": "Generally, the HSA is self-reported. The bank/financial provider will allow you to withdraw/spend whatever you want from your HSA. They report to the IRS the total that you withdrew for the year (your gross distributions) on a 1099-SA form. At tax time, you use a form 8889 to report this number of your gross distributions, and how much of it was used for medical expenses. Ideally, all of it was used for medical expenses. If it was not all for medical expenses, there will be extra taxes/penalties due. Different HSAs work differently, but for mine, which is held at a credit union, I can get money out several ways. I have an HSA checkbook and an HSA debit card that I can use anywhere. I can also transfer money out of my HSA into my regular checking account to reimburse myself for an expense, or even stop in at the teller window and take out cash. The credit union doesn't need to see any receipts for any of this. They don't care if I'm spending it at the doctor's office or the casino. It is up to me to make sure I'm spending the money in accordance to the law and that everything is reported correctly on my tax return. Nothing is verified unless you get audited. You definitely should keep documentation on the expenses, because if you are audited, you need to be prepared to account for every withdrawal. Make sure you are very familiar with the rules on eligible medical expenses, so you know what is allowed and what is not. IRS Publication 502 has all the details on what is allowed. As far as how it gets counted towards your deductible, you need to make sure that all of your medical bills get sent to your health insurance, even if you will eventually have to pay for it. For example, let's say you go to the doctor, and the bill is $150. Even if you know that the deductible is not met yet and you will be responsible for the entire $150, make sure the doctor's office submits the bill to your insurance. The insurance company will inform the doctor's office that you are responsible for all of it, but they will apply the amount towards your deductible.",
"title": ""
},
{
"docid": "546150",
"text": "I have managed two IRA accounts; one I inherited from my wife's 401K and my own's 457B. I managed actively my wife's 401 at Tradestation which doesn't restrict on Options except level 5 as naked puts and calls. I moved half of my 457B funds to TDAmeritrade, the only broker authorized by my employer, to open a Self Directed account. However, my 457 plan disallows me from using a Cash-secured Puts, only Covered Calls. For those who does not know investing, I resent the contention that participants to these IRAs should not be messing around with their IRA funds. For years, I left my 401k/457B funds with my current fund custodian, Great West Financial. I checked it's current values once or twice a year. These last years, the market dived in the last 2 quarters of 2015 and another dive early January and February of 2016. I lost a total of $40K leaving my portfolio with my current custodian choosing all 30 products they offer, 90% of them are ETFs and the rest are bonds. If you don't know investing, better leave it with the pros - right? But no one can predict the future of the market. Even the pros are at the mercy of the market. So, I you know how to invest and choose your stocks, I don't think your plan administrator has to limit you on how you manage your funds. For example, if you are not allowed to place a Cash-Secured Puts and you just Buy the stocks or EFT at market or even limit order, you buy the securities at their market value. If you sell a Cash-secured puts against the stocks/ETF you are interested in buying, you will receive a credit in fraction of a dollar in a specific time frame. In average, your cost to owning a stock/ETF is lesser if you buy it at market or even a limit order. Most of the participants of the IRA funds rely too much on their portfolio manager because they don't know how to manage. If you try to educate yourself at a minimum, you will have a good understanding of how your IRA funds are tied up to the market. If you know how to trade in bear market compared to bull market, then you are good at managing your investments. When I started contributing to my employer's deferred comp account (457B) as a public employee, I have no idea of how my portfolio works. Year after year as I looked at my investment, I was happy because it continued to grow. Without scrutinizing how much it grew yearly, and my regular payroll contribution, I am happy even it only grew 2% per year. And at this age that I am ready to retire at 60, I started taking investment classes and attended pre-retirement seminars. Then I knew that it was not totally a good decision to leave your retirement funds in the hands of the portfolio manager since they don't really care if it tanked out on some years as long at overall it grew to a meager 1%-4% because they managers are pretty conservative on picking the equities they invest. You can generalize that maybe 90% of IRA investors don't know about investing and have poor decision making actions which securities/ETF to buy and hold. For those who would like to remain as one, that is fine. But for those who spent time and money to study and know how to invest, I don't think the plan manager can limit the participants ability to manage their own portfolio especially if the funds have no matching from the employer like mine. All I can say to all who have IRA or any retirement accounts, educate yourself early because if you leave it all to your portfolio managers, you lost a lot. Don't believe much in what those commercial fund managers also show in their presentation just to move your funds for them to manage. Be proactive. If you start learning how to invest now when you are young, JUST DO IT!",
"title": ""
},
{
"docid": "544020",
"text": "When the inflation rate increases, this tends to push up interest rates because of supply and demand: If the interest rate is less than the inflation rate, then putting your money in the bank means that you are losing value every day that it is there. So there's an incentive to withdraw your money and spend it now. If, say, I'm planning to buy a car, and my savings are declining in real value, then if I buy a car today I can get a better car than if I wait until tomorrow. When interest rates are high compared to inflation, the reverse is true. My savings are increasing in value, so the longer I leave my money in the bank the more it's worth. If I wait until tomorrow to buy a car I can get a better car than I would be able to buy today. Also, people find alternative places to keep their savings. If a savings account will result in me losing value every day my money is there, then maybe I'll put the money in the stock market or buy gold or whatever. So for the banks to continue to get enough money to make loans, they have to increase the interest rates they pay to lure customers back to the bank. There is no reason per se for rising interest rates to consumers to directly cause an increase in the inflation rate. Inflation is caused by the money supply growing faster than the amount of goods and services produced. Interest rates are a cost. If interest rates go up, people will borrow less money and spend it on other things, but that has no direct effect on the total money supply. Except ... you may note I put a bunch of qualifiers in that paragraph. In the United States, the Federal Reserve loans money to banks. It creates this money out of thin air. So when the interest that the Federal Reserve charges to the banks is low, the banks will borrow more from the Feds. As this money is created on the spot, this adds to the money supply, and thus contributes to inflation. So if interest rates to consumers are low, this encourages people to borrow more money from the banks, which encourages the banks to borrow more from the Feds, which increases the money supply, which increases inflation. I don't know much about how it works in other countries, but I think it's similar in most nations.",
"title": ""
},
{
"docid": "206597",
"text": "The rebate amount is a non-qualified distribution: IRS Pub 969 describes how the HSA works: Reporting Distributions on Your Return How you report your distributions depends on whether or not you use the distribution for qualified medical expenses (defined earlier). If you use a distribution from your HSA for qualified medical expenses, you do not pay tax on the distribution but you have to report the distribution on Form 8889. However, the distribution of an excess contribution taken out after the due date, including extensions, of your return is subject to tax even if used for qualified medical expenses. Follow the instructions for the form and file it with your Form 1040 or Form 1040NR. If you do not use a distribution from your HSA for qualified medical expenses, you must pay tax on the distribution. Report the amount on Form 8889 and file it with your Form 1040 or Form 1040NR. If you have a taxable HSA distribution, include it in the total on Form 1040 or Form 1040NR, line 21, and enter “HSA” and the amount on the dotted line next to line 21. You may have to pay an additional 20% tax on your taxable distribution. I looked at several plans regarding how to handle mistaken distributions: example A What if I accidentally use my HSA Visa debit card for a non-qualified expense? To fix this problem, just bring that same amount into any local branch and tell us it was a Mistaken Distribution. We can then put the funds back into your HSA and correct the problem. example B You’re allowed to correct mistaken HSA withdrawals when there is clear and convincing evidence that amounts were distributed from an HSA because of a mistake of fact due to reasonable cause. You can correct the mistake by repaying the withdrawal no later than April 15 following the first year that you knew or should have known that the withdrawal was a mistake. When a correction is made, the mistaken withdrawal does not have to be included in gross income or be subject to the 6 percent additional tax, and the repayment does not count as an excess contribution. If an error is made by SelectAccount in its role as the administrator, SelectAccount will be responsible for taking appropriate corrective action. Check with your plan trustee on their procedure to fix the mistaken withdrawal.",
"title": ""
},
{
"docid": "344928",
"text": "\"Wyoming is a good state for this. It is inexpensive and annual compliance is minimal. Although Delaware has the best advertising campaign, so people know about it, the reality is that there are over 50 states/jurisdictions in the United States with their own competitive incorporation laws to attract investment (as well as their own legislative bodies that change those laws), so you just have to read the laws to find a state that is favorable for you. What I mean is that whatever Delaware does to get in the news about its easy business laws, has been mimicked and done even better by other states by this point in time. And regarding Delaware's Chancery Court, all other states in the union can also lean on Delaware case law, so this perk is not unique to Delaware. Wyoming is cheaper than Delaware for nominal presence in the United States, requires less information then Delaware, and is also tax free. A \"\"registered agent\"\" can get you set up and you can find one to help you with the address dilemma. This should only cost $99 - $200 over the state fees. An LLC does not need to have an address in the United States, but many registered agents will let you use their address, just ask. Many kinds of businesses still require a bank account for domestic and global trade. Many don't require any financial intermediary any more to receive payments. But if you do need this, then opening a bank account in the United States will be more difficult. Again, the registered agent or lawyer can get a Tax Identification Number for you from the IRS, and this will be necessary to open a US bank account. But it is more likely that you will need an employee or nominee director in the United States to go in person to a bank and open an account. This person needs to be mentioned in the Operating Agreement or other official form on the incorporation documents. They will simply walk into a bank with your articles of incorporation and operating agreement showing that they are authorized to act on behalf of the entity and open a bank account. They then resign, and this is a private document between the LLC and the employee. But you will be able to receive and accept payments and access the global financial system now. A lot of multinational entities set up subsidiaries in a number of countries this way.\"",
"title": ""
},
{
"docid": "427472",
"text": "First, welcome to Money.SE. If you are interested in saving and investing, this is a great site to visit. Please take the tour and just start to read the questions you find interesting. 1 - even though this is hypothetical, it scales down to an average investor. If I own 1000 shares of the 1 billion, am I liable if the company goes under? No. Stocks don't work that way. If all I have is shares, not a short position, not options, I can only see my investment go to zero. 2 - Here, I'd ask that you edit your country in the tags. I can tell you that my newborn (who is soon turning 17) had a stock account in her name when she was a few months old. It's still a custodian account, meaning an adult has to manage it, and depending on the state within the US, the age that it's hers with no adult, is either 18 or 21. Your country may have similar regional rules. Also - each country has accounts specifically geared toward retirement, with different favorable rules regarding taxation. In the US, we have accounts that can be funded at any age, so long as there's earned income. My daughter started one of these accounts when she started baby sitting at age 12. She will have more in her account by the time she graduates college than the average retiree does. It's good for her, and awful for the general population that this is the case.",
"title": ""
},
{
"docid": "427631",
"text": "In addition to having separate income for federal and state tax purposes, things can get really complicated if you ever have capital gains and losses. Suppose you sell taxable stocks for a loss of $5000, and meanwhile, have capital gains of $1000 in your HSA. From the federal perspective, the gains in the HSA don't exist, so you deduct $3000 of the loss, and then carry over the remaining $2000. However, from the state perspective, $1000 of the capital loss went to canceling out the gains in the HSA. Therefore, you only carry over $1000. Assuming you continue to have losses and gains, this will carry on forever. You'll have to track completely independent sets of gains and losses and carryover losses for federal and state purposes forever, even if you no longer use the HSA. Therefore, I'd recommend not investing HSA proceeds at all if you live in a state that doesn't recognize HSAs. It's just too complicated to be worth it, especially since your provider won't track any of this for you.",
"title": ""
},
{
"docid": "115968",
"text": "Is this even legal? How can a bank refuse to deposit legal tender in the United States? Legal for all debts, public or private, doesn't mean quite what I used to think, either. Per The Fed: This statute means that all United States money as identified above is a valid and legal offer of payment for debts when tendered to a creditor. There is, however, no Federal statute mandating that a private business, a person, or an organization must accept currency or coins as payment for goods or services. Private businesses are free to develop their own policies on whether to accept cash unless there is a state law which says otherwise. Yes, they can refuse loose change. Also, they aren't refusing your deposit, just requiring that it be rolled. What do I do with my change? I do not want to spend the time rolling it, and I am not going to pay a fee to cash my change. There aren't many other options, change is a nuisance. I believe Coinstar machines reduce/remove their fee if you exchange coins for gift cards, so that might be the best option for convenience and retaining value.",
"title": ""
},
{
"docid": "151838",
"text": "\"It's very hard to measure the worth of an abstract concept like money, particularly over long periods of time. In the modern era we have things like the Consumer Price Index (CPI) in the United States, where the Bureau of Labor Statistics literally sends \"\"shoppers\"\" out to find prices of things and surveys people to find out what they buy. This results in a variety of \"\"indexes\"\" which variously get reported by media outlets as \"\"inflation\"\" (or \"\"deflation\"\" if the change in value goes the other way). There are also other measurements available like the MIT Billion Prices Project which attempt to make their own reading of the \"\"worth\"\" of currencies. Those kinds of things are about the only ways to measure a currency's change in \"\"value to itself\"\" because a currency is basically only worth what one can buy with it. While it isn't \"\"all the world's currencies combined\"\", there is a concept of the International Monetary Fund's \"\"Special Drawing Rights (SDR)\"\", which is a basket of five currencies used by world central banks to help \"\"back\"\" each other's currencies, and is (very) occasionally used as a unit of currency for international contracts. One might be able to compare the price of one currency to that of the SDR, or even to any other weighted average of world currencies that one wanted, but I don't think it's done nearly as often as comparing currencies to the basket of goods one can buy to find \"\"inflation\"\". Even though one might think what would be important to measure would be overall Money Supply Inflation, much more often people care more about measuring Price Inflation. (Occasionally people worry about Wage Inflation, but generally that's considered a result of high Price Inflation.) In order to try to keep this on topic as a \"\"personal finance\"\" thing rather than an \"\"economics\"\" thing, I guess the question is: Why do you want to know? If you have some assets in a particular currency, you probably care most about what you'll be able to buy with them in the future when you want or need to spend them. In that sense, it's inflation that you're likely caring about the most. If you're trying to figure out which currency to keep your assets in, it largely depends on what currency your future expenses are likely to be in, though I can imagine that one might want to move out of a particular currency if there's a lot of political instability that you're expecting to lead to high inflation in a currency for a time.\"",
"title": ""
},
{
"docid": "167438",
"text": "Congrats! That's a solid accomplishment for someone who is not even in college yet. I graduated college 3 years ago and I wish I was able to save more in college than I did. The rule of thumb with saving: the earlier the better. My personal portfolio for retirement is comprised of four areas: Roth IRA contributions, 401k contributions, HSA contributions, Stock Market One of the greatest things about the college I attended was its co-op program. I had 3 internships - each were full time positions for 6 months. I strongly recommend, if its available, finding an internship for whatever major you are looking into. It will not only convince you that the career path you chose is what you want to do, but there are added benefits specifically in regards to retirement and savings. In all three of my co-ops I was able to apply 8% of my paycheck to my company's 401k plan. They also had matching available. As a result, my 401k had a pretty substantial savings amount by the time I graduated college. To circle back to your question, I would recommend investing the money into a Roth IRA or the stock market. I personally have yet to invest a significant amount of money in the stock market. Instead, I have been maxing out my retirement for the last three years. That means I'm adding 18k to my 401k, 5.5k to my Roth, and adding ~3k to my HSA (there are limits to each of these and you can find them online). Compounded interest is amazing (I'm just going to leave this here... https://www.moneyunder30.com/power-of-compound-interest).",
"title": ""
},
{
"docid": "300438",
"text": "The account doesn't have to be associated with a specific health plan. There are some accounts that work that way. In fact, mine does. But I didn't go to a bank and open it up, it came as a package deal with my employer's health plan. Furthermore I don't contribute to it, the company does. If I wish to contribute my own funds, I have a separate Flexible Spending Account (FSA). This is not tied to my health plan. I can make qualified purchases at Wal Mart, Target, or wherever I choose. Then I can submit the receipts for reimbursement. In your case it sounds like your HSA works more like my FSA. The relevant question here is 'How do I (you) withdraw funds from the HSA?' There are a few different possibilities. Some accounts have a debit card, some give you checks, some have a reimbursement process similar to my FSA. (Some have more than one option available.) In your case you should contact Bank of America to determine how to withdraw funds from your account.",
"title": ""
},
{
"docid": "547401",
"text": "Yes, you are generally allowed to make contributions yourself to your HSA, even if your employer also made contributions. Let me explain further. The contribution limit for tax year 2015 is $3350 for individual coverage. (It is higher for family coverage, or for account holders age 55+.) The limit is for everything contributed to the HSA, whether it is an employer contribution or an account holder contribution. (In other words, if your limit is $3350, and your employer contributed $3000, you can only contribute $350.) As far as the IRS is concerned, anything that your employer sends in is considered an employer contribution. This might be money from the company as part of a benefit, or it might be money deducted from your salary as part of a voluntary contribution on your part. Either way, if the employer sends it in, it is an employer contribution. None of this employer contribution shows up on your W-2 as taxable income, so you don't get to deduct it on your tax return. It has already been taken off of your income. Money that you send in yourself with your after-tax dollars is your account holder contribution. This is money that you can deduct on your tax return, so that you aren't paying tax on this money. So here is what you need to do: Determine your total HSA contribution limit for tax year 2015. Find out how much your employer has already contributed for 2015. The difference is how much you can still contribute for 2015. Contact your HSA provider and find out how to make a 2015 contribution. Don't just send money in, because there is probably a form they want you to fill out to make a prior year contribution. Get all this done by April 15, the deadline for making a prior year contribution. Actually, get it done before April 15, because often there will be some sort of delay of a day or two that will prevent you from doing this on the last day.",
"title": ""
},
{
"docid": "226976",
"text": "\"The \"\"must be postmarked\"\" language might be just from the old bank itself, not from the IRS. The language I see in Publication 969 only says \"\"You can make contributions to your HSA for 2014 until April 15, 2015.\"\" In this case, it is understandable that the credit union you have the new account with does not want to accept the contribution for tax year 2014. You didn't have an account with them in 2014. You didn't even send out the paperwork to them to open the account until last week, and they didn't open your account until this week, after the deadline. It is unfortunate, but I don't think you'll be able to force them to do anything differently here. It is just too late. I do know how that feels. I had a somewhat similar circumstance with my HSA, the first year I had the account. I contributed money to the HSA using my credit union's website, transferring money from my checking account into my HSA, as I was told to do. In January and February of the following year, I made more contributions this way, thinking that I was making them for the previous tax year. However, they never got coded correctly by the credit union, and I later found out that the credit union counted those as contributions for the current year. As a result, I was essentially denied the full contribution limit for that year, and had a bit of a paperwork nightmare. Now, if I have to make a prior year contribution, I only make it in person, and they have a form they have me fill out each time I do.\"",
"title": ""
}
] |
2312
|
In what state should I register my web-based LLC?
|
[
{
"docid": "596973",
"text": "Register in Nevada. It's a no brainer. I understand that it's not a great deal of money, but if you can save several hundred dollars per year, why not? It's the same amount (actually probably less) of paperwork to register in Nevada.",
"title": ""
},
{
"docid": "407844",
"text": "I would prefer to see you register in your home state, and then focus on making money, rather than spending time looking to game the system to save a few bucks. People worry way too much about these trivial fees when they should be focused on making their business successful. Get registered, get insurance, and then pour it on and start making money. Make $650 your target for a week's income - you can do it! Next year's goal should be spending $50 a month on a payroll service because you're SO BUSY you can't take the extra time to pay your own social security taxes.",
"title": ""
},
{
"docid": "585899",
"text": "In this case not only that you must register in California (either as domestic, or as foreign if you decided to form elsewhere), you'll also be on the hook for back-taxes if you didn't do it from the start. FTB is notorious for going after out-of-state LLCs that Californians open in other States trying to avoid the $800 fee.",
"title": ""
},
{
"docid": "440506",
"text": "I have researched this question extensively in previous years as we have notoriously high taxes in California, while neighboring a state that has zero corporate income tax and personal income tax. Many have attempted pull a fast one on the California taxation authorities, the Franchise Tax Board, by incorporating in Nevada or attempting to declare full-year residence in the Silver State. This is basically just asking for an audit, however. California religiously examines taxpayers with any evidence of having presence in California. If they deem you to be a resident in California, and they likely will based on the fact that you live in California (physical presence), you will be subject to taxation on your worldwide income. You could incorporate in Nevada or Bangladesh, and California will still levy its taxation on any business income (Single Member LLCs are disregarded as separate corporate entities, but still taxed at ordinary income rates on the personal income tax basis). To make things worse, if California examines your Single Member LLC and finds that it is doing business in California, based on the fact that its sole owner is based in California all year long, you could feasibly end up with additional penalties for having neglected to file your LLC in California (California LLCs are considered domestic, and only file in California unless they wish to do business in other states; Nevada LLCs are considered foreign to California, requiring the owner to file a domestic LLC organization in Nevada and then a foreign LLC organization in California, which still gets hit with the minimum $800 franchise fee because it is a foreign LLC doing business in California). Evading any filing responsibility in California is not advisable. FTB consistently researches LLCs, S-Corporations and the like to determine whether they've been organized out-of-state but still principally operated in California, thus having a tax nexus with California and the subsequent requirement to be filed in California and taxed by California. No one likes paying taxes, and no one wants to get hit with franchise fees, especially when one is starting a new venture and that minimum $800 assessment seems excessive (in other words, you could have a company that earns nothing, zero, zip, nada, and still has to pay the $800 minimum fee), but the consequences of shirking tax laws and filing requirements will make the franchise fee seem trivial in comparison. If you're committed to living in California and desire to organize an LLC or S-Corp, you must file with the state of California, either as a domestic corporation/LLC or foreign corporation/LLC doing business in California. The only alternatives are being a sole proprietor (unincorporated), or leaving the state of California altogether. Not what you wanted to hear I'm sure, but that's the law.",
"title": ""
},
{
"docid": "583519",
"text": "Is it really necessary? If $800 / year registration fee is too much to you, an LLC is apparently not something you need right now. Many people conduct web-based business online on personal terms. My suggestion is that you focus on your business first and try to grow it as much as you can before you get down to a company.",
"title": ""
},
{
"docid": "397291",
"text": "In GA, LLC fees are $50 a year. Incorporating is a one time $100 fee. This information is current as of September 2013.",
"title": ""
}
] |
[
{
"docid": "510701",
"text": "\"The primary advantage is protection of your personal assets. If your LLC gets sued, they can't take your house/car/dog/wife. There aren't really any financial incentives to be an LLC; because of the pass-thru taxing structure, you wind up paying the same in taxes either way. \"\"The cost\"\" will depend on where you're located, and usually involves a few factors -- Expect to pay $300-500 to start it, depending on your state and who you register with (technically, you can usually register for free at the secretary of state, but wouldn't you rather pay an expert?), and \"\"State Franchise Tax\"\", which will can be a minimum of up to $1000/year depending on the state, plus even more if your LLC earns more than $xxx,000. EDIT -- As an aside, I'll mention that I'm based in California, and our state franchise tax starts at $800/yr. I'm all-web-based, so I've been investigating incorporating in Nevada or Delaware instead (no franchise tax, lower filing fees), but from what I've found, it's hardly worth the trouble. In addition to having to pay a Registered Agent (someone to act as my permanent mailing address in that state for ~$100/yr), apparently California likes to search for people just like me, and charge them $800 anyway. You can fight that, of course, and claim that your business really is done in Nevada, but do you really want to?\"",
"title": ""
},
{
"docid": "232563",
"text": "\"Yes, you can use a post office box as a business address but not as an address for your registered agent. Using your home address as the address of the business does not, to my knowledge, create a legal issue if you are sued. Your home is a personal asset, not one that belongs to the LLC, so it would not be subject to seizure or forfeiture as part of any lawsuit against the business itself. Every state requires an LLC or corporation to have a \"\"registered agent\"\" which, according to Wikipedia is: In United States business law, a registered agent, also known as a resident agent or statutory agent, is a business or individual designated to receive service of process (SOP) when a business entity is a party in a legal action such as a lawsuit or summons. You can be your own registered agent if you like. Companies that provide incorporation services will usually offer to act as a registered agent for your new business for a fee, but it's really no big deal. I would recommend that you go to the NoLo.com web site section about forming an LLC and take a look at their resources to help you through this. You need to do it right, so understand what you need to do for the state you live in, and take your time. If you rush it and screw it up then you might regret it later. I hope this helps Good luck!\"",
"title": ""
},
{
"docid": "564475",
"text": "\"You can file an LLC yourself in most states, although it might be helpful to use a service if you're not sure what to do to ensure it is correct. I filed my LLC here in Colorado online with the Secretary of State's office, which provided the fill-in-the-blank forms and made it easy. In the U.S., taxation of an LLC is \"\"pass-through\"\", meaning the LLC itself does not have any tax liability. Taxes are based on what you take out of the LLC as distributions to yourself, so you pay personal income tax on that. There are many good books on how to form and then operate an LLC, and I personally like NoLo (link to their web site) because they cater to novices. As for hiring people in India, I can't speak to that, so hopefully someone else can answer that specific topic. As for what you need to know about how to run it, I'll refer back to the NoLo books and web site.\"",
"title": ""
},
{
"docid": "85622",
"text": "\"Assuming you are talking about an LLC in the United States, there are no tax repercussions on the LLC itself, because LLCs use pass-through taxation in the U.S., meaning that the LLC does not pay taxes. Whatever you take out of the LLC in the form of distributions goes onto your personal income tax as ordinary income, and you pay personal income tax on it. See this link on the subject from the Nolo.com web site: Tax treatment of an LLC from the Nolo.com web site Repayment of your loan by the LLC would just be another business expense for the business itself. I guess the question would then turn on what your personal tax repercussion would be for payments received from the LLC on the loan. I would guess (and I emphasize \"\"guess\"\") that you would pay tax on any interest gain from the loan payments, which makes the assumption you made the loan to include interest. If not (in other words, if you made this an interest-free loan) then it would be considered a wash for tax purposes and you would have no tax liability for yourself. To reiterate, the LLC (if it is a U.S.. entity) does not pay taxes. Taxation of LLC income is based on whatever distributions the principals take out of it, which is then claimed as taxable personal income. My apologies to littleadv for not making my prior answer (I deleted it) more clear about my answer assuming you were speaking of a U.S.-chartered LLC. I hope this helps. Good luck!\"",
"title": ""
},
{
"docid": "222726",
"text": "\"What is the right way to handle this? Did you check the forms? Did the form state $0 tax due on the FTB LLC/Corp form (I'm guessing you operate as LLC/Corp, since you're dealing with the Franchise Tax)? The responsibility is ultimately yours. You should cross check all the numbers and verify that they're correct. That said, if the CPA filled the forms incorrectly based on your correct data - then she made a mistake and can be held liable. CPA filing forms from a jurisdiction on the other end of the country without proper research and knowledge may be held negligent if she made a grave mistake. You can file a law suit against the CPA (which will probably trigger her E&O insurance carrier who'll try to settle if there's a good chance for your lawsuit to not be thrown away outright), or complain to the State regulatory agency overseeing CPAs in the State of her license. Or both. Am I wrong for expecting the CPA should have properly filled out and filed my taxes? No, but it doesn't shift the responsibility from you. How can I find out if the CPA has missed anything else? Same as with doctors and lawyers - get a second opinion. Preferably from a CPA licensed in California. You and only you are responsible for your taxes. You may try to pin the penalties and interest on the CPA if she really made a mistake. California is notorious for very high LLC/Corp franchise tax (cost of registering to do business in the State). It's $800 a year. You should have read the forms and the instructions carefully, it is very prominent. It is also very well discussed all over the Internet, any search engine would pop it up for you with a simple \"\"California Franchise Tax for LLC/Corp\"\" search. CA FTB is also very aggressive in assessing and collecting the fee, and the rules of establishing nexus in CA are very broad. From your description it sounds like you were liable for the Franchise tax in CA, since you had a storage facility in CA. You may also be liable for sales taxes for that period.\"",
"title": ""
},
{
"docid": "237514",
"text": "\"There are very few circumstances where forming an out of state entity is beneficial, but a website is within these circumstances in certain instances. Businesses with no physical operations do not need to care what jurisdiction they are registered in: your home state, a better united state or non-united state. The \"\"limited liability\"\" does it's job. If you are storing inventory or purchasing offices to compliment your online business, you need to register in the state those are located in. An online business is an example of a business with no physical presence. All states want you to register your LLC in the state that you live in, but this is where you need to read that state's laws. What are the consequences of not registering? There might be none, there might be many. In New York, for example, there are no consequences for not registering (and registering in new york - especially the city - is likely the most expensive in the USA). If your LLC needs to represent itself in court, New York provides retroactive foreign registrations and business licenses. So basically, despite saying that you need to pay over $1000 to form your LLC \"\"or else\"\", the reality is that you get the local limited liability protection in courts whenever you actually need it. Check your local state laws, but more times than not it is analogous to asking a barber if you need a haircut, the representative is always going to say \"\"yes, you do\"\" while the law, and associated case law, reveals that you don't. The federal government doesn't care what state your form an LLC or partnership in. Banks don't care what state you form an LLC or partnership in. The United States post office doesn't care. Making an app? The Apple iTunes store doesn't care. So that covers all the applicable authorities you need to consider. Now just go with the cheapest. In the US alone there are 50 states and several territories, all with their own fee structures, so you just have to do your research. Despite conflicting with another answer, Wyoming is still relevant, because it is cheap and has a mature system and laws around business entity formation. http://www.incorp.com has agents in every state, but there are registered agents everywhere, you can even call the Secretary of State in each state for a list of registered agents. Get an employer ID number yourself after the business entity is formed, it takes less than 5 minutes. All of this is also contingent on how your LLC or partnership distributes funds. If your LLC is not acting like a pass through entity to you and your partner,but instead holding its own profits like a corporation, then again none of this matters. You need to form it within the state you live and do foreign registrations in states where it has any physical presence, as it has becomes its own tax person in those states. This is relevant because you said you were trying to do something with a friend.\"",
"title": ""
},
{
"docid": "97083",
"text": "\"especially considering it has a mortgage on it (technically a home equity loan on my primary residence). I'm not following. Does it have a mortgage on it, or your primary residence (a different property) was used as a security for the loan? If it is HELOC from a different property - then it is really your business what to do with it. You can spend it all on casinos in Vegas for all that the bank cares. Is this a complicated transaction? Any gotchas I should be aware of before embarking on it? Obviously you should talk to an attorney and a tax adviser. But here's my two cents: Don't fall for the \"\"incorporate in Nevada/Delaware/Wyoming/Some other lie\"\" trap. You must register in the State where you live, and in the State where the property is. Incorporating in any other State will just add complexity and costs, and will not save you anything whatsoever. 2.1 State Taxes - some States tax LLCs. For example, in California you'll pay at least $800 a year just for the right of doing business. If you live in California or the property is in California - you will pay this if you decide to set up an LLC. 2.2 Income taxes - make sure to not elect to tax your LLC as a corporation. The default for LLC is \"\"disregarded\"\" status and it will be taxed for income tax purposes as your person. I.e.: IRS doesn't care and doesn't know about it (and most States, as well). If you actively select to tax it as a corporation (there's such an option) - it will cost you very dearly. So don't, and if someone suggest such a thing to you - run away from that person as fast as you can. Mortgages - it is very hard to get a mortgage when the property is under the LLC. If you already have a mortgage on that property (the property is the one securing the loan) - it may get called once you transfer it into LLC, since from bank's perspective that would be transferring ownership. Local taxes - transferring into LLC may trigger a new tax assessment. If you just bought the property - that will probably not matter much. If it appreciated - you may get hit with higher property taxes. There are also many little things - once you're a LLC and not individual you'll have to open a business bank account, will probably need a new insurance policy, etc etc. These don't add much to costs and are more of an occasional nuisance.\"",
"title": ""
},
{
"docid": "192332",
"text": "\"Since as you say, an LLC is a pass-through entity, you will be making income in the U.S. when you sell to U.S. customers. And so you will need to file the appropriate personal tax forms in the US. As well as potentially in one or more States. The US government does not register LLCs. The various States do. So you'll be dealing with Oregon, Wisconsin, Wyoming, one of those for the LLC registration. You will also need to have a registered agent in the State. That is a big deal since the entire point of forming an LLC is to add a liability shield. You would lose the liability shield by not maintaining the business formalities. Generally nations aim to tax income made in their nation, and many decline to tax income that you've already paid taxes on in another nation. A key exception: If money is taxed by the U.S. it may also be taxed by one of the States. Two States won't tax the same dollar. Registering an LLC in one State does not mean you'll pay state taxes there. Generally States tax income made in their State. It's common to have a Wyoming LLC that never pays a penny of tax in Wyoming. Officially, an LLC doing business in a State it did not form in, must register in that State as a \"\"foreign LLC\"\" even though it's still in the USA. The fee is usually the same as for a domestic LLC. \"\"Doing business\"\" means something more than incidental sales, it means having a presence specifically in the State somehow. It gets complicated quick. If you are thinking of working in someone's app ecosystem like the Apple Store, Google Play, Steam etc. Obviously they want their developers coding, not wrestling with legalities, so some of them make a priority out of clearing and simplifying legal nuisances for you. Find out what they do for you.\"",
"title": ""
},
{
"docid": "339463",
"text": "If I hire someone in Utah to do sales for me over the phone, and he works out of his home, am I required to register an LLC or file my current one as a foreign entity in Utah? Yes, since you've established presence in Utah. You'll register your current LLC in Utah, no point creating another one. If my sales guy, or I, call businesses in, say, Florida, and sell a few businesses our services for online work like maybe a website design, etc. Are we required to file our LLC In Florida as either a new LLC or a foreign one? No, you need to register where you (your company, including your employees or physical offices) are physically present. You don't need to register in any state you ship products or provide services to. If no-one of your company's employees is present in Florida and you don't have an office/rent a storage there - then you have no presence in Florida. If you actually go there to provide the services - then you do.",
"title": ""
},
{
"docid": "507811",
"text": "\"Can I rent a mailbox at UPS Store and use it as a physical business address? Depending on the type of business, this may not be allowed. However, there's no blanket restriction, so you need to check if for business of the type that you have this is not forbidden. In any case, there's \"\"business address\"\" and there's \"\"address of records\"\". The former can, for most part, be a PO box. The latter usually cannot. Check if Virginia requires \"\"address of records\"\" to be provided. Can I use my home address as a registered agent address? If yes, would my house be considered as a business property? or registered address is just an address that gonna receive mails from the government state? Yes, you can be your LLCs registered agent. The registered agent must be able to accept official deliveries during the regular business hours. PO box cannot be used for that purpose, it must be a physical address where there's someone present to sign for you when you're served with lawsuits and notices. If you are not at home during the regular business hours - you cannot provide your home address for that purpose. You will be using your home for business purposes, whether you're serving as your own registered agent or not. So depending on your county/city laws - it is likely that your home will be considered place of business either way. Can I use UPS mailbox store for both business address and registered agent? See above. What other options should I consider? You can hire a register agent in your State, it is usually $50-$100/year. They will scan whatever they receive and forward to you, usually within hours. Some also provide mail forwarding service (i.e.: they'll forward any mail for you, not only official correspondence), but that usually costs extra.\"",
"title": ""
},
{
"docid": "90290",
"text": "I think you're making a mistake. If you still want to make this mistake (I'll explain later why I think its a mistake), the resources for you are: IRS.GOV - The IRS official web site, that has all the up-to-date forms and instructions for them, guiding publications and the relevant rules. You might get a bit overwhelmed through. Software programs - TurboTax (Home & Business for a sole propriator or single member LLC, Business for more complicated business), or H&R Block Business (only one version that should cover all) are for your guidance. They provide tips and interactive guidance in filling in all the raw data, and produce all the forms filled for you according to the raw data you entered. I personally prefer TurboTax, I think its interface is nicer and the workflow is more intuitive, but that's my personal preference. I wrote about it in my blog last year. Both also include plug-ins for the state taxes (If I remember correctly, for both the first state is included in the price, if you need more than 1 state - there's extra $30-$40 per state). Your state tax authority web site (Minnesota Department of Revenue in your case). Both Intuit and H&R Block have on-line forums where people answer each others questions while using the software to prepare the taxes, you might find useful information there. As always, Google is your friend. Now, why I think this is a mistake. Mistakes that you make - will be your responsibility. If you use the software - they'll cover the calculation mistakes. But if you write income in a wrong specification or take a wrong deduction that you shouldn't have taken - it will be on your head and you're the one to pay the fines and penalties for that. Missed deductions and credits - CPA's (should) know about all the latest deductions and credits that you or your business might be entitled to. They also (should) know which one got canceled and you shouldn't be continuing taking them if you had before. Expenses - there are plenty of rules of what can be written off as an expense and how. Some things should be written off this year, others over several years, for some depreciation formula should be used, etc etc. Tax programs might help you with that, but again - mistakes are your responsibility. Especially for the first time and for the newly formed business, I think you should use a (good!) CPA. The CPA should take responsibility over your filing. The CPA should provide guarantee that based on the documents you provided, he filled all the necessary forms correctly, and will absorb all the fees and penalties if there's an audit and mistakes were found not because you withheld information from your CPA, but because the CPA made a mistake. That costs money, and that's why the CPA's are more expensive than using a program or preparing yourself. But, the risk is much higher, especially for a new business. And after all - its a business expense.",
"title": ""
},
{
"docid": "206114",
"text": "\"Generally, you pick the State which you're located at, because you'll have to register your LLC there in any case. In your case that would be either Colorado or Oklahoma - register as domestic in one, as foreign in the other. If your concern is anything other than mere convenience/costs - then you need to talk to a lawyer, however most State LLC laws are fairly alike (and modeled after the \"\"Uniform Limited Liability Company Act\"\". Keep in mind that most of the sites talking about \"\"forming LLC out of state\"\" are either sales sites or targeted to foreigners attempting to form a US company. All the cr@p you hear about forming in Delaware/Nevada/Wyoming - is useless and worthless for someone who's a resident of any of the US States. If you're a US resident - you will always have to register in the State you're located at and do the work at, so if you register elsewhere - you just need to register again in your home State. In your case you already span across States, so you'll have to register in two States as it is - why add the costs of registering in a third one?\"",
"title": ""
},
{
"docid": "258611",
"text": "The cost will be around $300-$500 if you do it correctly it in Florida and can be over a $1,000 if you do it in New York (New York is more expensive due to a publication requirement that New York has for LLC’s). The price ranges I’ve given include filing, state fees, getting a tax ID number (EIN), operating agreement, membership certificates, registered agent fees and publication fees if done in New York. Each state also have licensing boards and city fees that are applicable, so you would want to also make sure that you are keeping compliant there. Yearly paperwork to keep the LLC running won’t be so expensive, expect the state to charge a yearly fee and require some basic information to be submitted. I had a quick look at Florida, and with someone filing it for you, expect around $200 to $250 a year, plus registered agent fees. If you are late in Florida the penalty is $400 so you definitely would want a service that provides compliance calendar notifications to make sure you are on time with fees. In regards to bookkeeping and taxes, yearly tax filing will start at $250 to $500 for an LLC and move up from there depending on the services being offered and the amount of time of work. I recently referred someone to an accountant that will charge $250 to file an almost zero tax return on an LLC. I think $40 an hour is a little low for a bookkeeper but it all depends on where you are. I know in some major cities bookkeepers expect $75 an hour or higher. So the expectation in Miami and Manhattan will probably be more expensive than Jacksonville and Albany. If you doing a little business don’t expect the cost to be too much on the bookkeeping. So, breakdown: $300-$500 (FL) - $1,000 (NY) Registration of LLC + any business license, city or other registrations $250 Yearly Fee + Yearly Registered Agent + any business licenses, city or other fee $500 Tax Return + Bookkeeping Fee Banks will charge more than a personal account so expect $120 a year plus. In regards to service I would look at companies that specialize in foreigners setting up businesses in the US, because they will have services designed to help you more than services that primarily specialize with US clients. You are going to have some different needs, based on not having a Social Security Number or establishing from overseas.",
"title": ""
},
{
"docid": "344928",
"text": "\"Wyoming is a good state for this. It is inexpensive and annual compliance is minimal. Although Delaware has the best advertising campaign, so people know about it, the reality is that there are over 50 states/jurisdictions in the United States with their own competitive incorporation laws to attract investment (as well as their own legislative bodies that change those laws), so you just have to read the laws to find a state that is favorable for you. What I mean is that whatever Delaware does to get in the news about its easy business laws, has been mimicked and done even better by other states by this point in time. And regarding Delaware's Chancery Court, all other states in the union can also lean on Delaware case law, so this perk is not unique to Delaware. Wyoming is cheaper than Delaware for nominal presence in the United States, requires less information then Delaware, and is also tax free. A \"\"registered agent\"\" can get you set up and you can find one to help you with the address dilemma. This should only cost $99 - $200 over the state fees. An LLC does not need to have an address in the United States, but many registered agents will let you use their address, just ask. Many kinds of businesses still require a bank account for domestic and global trade. Many don't require any financial intermediary any more to receive payments. But if you do need this, then opening a bank account in the United States will be more difficult. Again, the registered agent or lawyer can get a Tax Identification Number for you from the IRS, and this will be necessary to open a US bank account. But it is more likely that you will need an employee or nominee director in the United States to go in person to a bank and open an account. This person needs to be mentioned in the Operating Agreement or other official form on the incorporation documents. They will simply walk into a bank with your articles of incorporation and operating agreement showing that they are authorized to act on behalf of the entity and open a bank account. They then resign, and this is a private document between the LLC and the employee. But you will be able to receive and accept payments and access the global financial system now. A lot of multinational entities set up subsidiaries in a number of countries this way.\"",
"title": ""
},
{
"docid": "32057",
"text": "You need to first visit the website of whatever state you're looking to rent the property in and you're going to want to form the LLC in that particular state. Find the Department of Licensing link and inquire about forming a standard LLC to register as the owner of the property and you should easily see how much it costs. If the LLC has no income history, it would be difficult for the bank to allow this without requiring you to personally guarantee the loan. The obvious benefit of protecting yourself with the LLC is that you protect any other personal assets you have in your name. Your liability would stop at the loan. The LLC would file its own taxes and be able to record the income against the losses (i.e. interest payments and other operating expenses.). This is can be beneficial depening on your current tax situation. I would definitely recommend the use of a tax accountant at that point. You need to be sure you can really afford this property in the worst case scenario and think about market leasing assumption, property taxes, maintenance and management (especially if you've moved to another state.)",
"title": ""
},
{
"docid": "197501",
"text": "There is no such thing as double taxation. If you pay tax in the US, you CAN claim tax credits from India tax authority. For example, if you pay 100 tax in USA and your tax liability in India is 200, then you will only pay 100 (200 India tax liability minus 100 tax credits on foreign tax paid in the USA). This is always true and not depending on any treaty. If there is a treaty, the tax rate in the United States is set on the treaty and you CAN claim that final tax rate based upon that treaty. If you operate an LLC, and the income is NOT derived from United States and you have no ties with the US and that LLC is register to a foreign person (not company but a real human) then you will not have to submit tax return in the US... I advice you to read this: http://www.irs.gov/businesses/small/article/0,,id=98277,00.html",
"title": ""
},
{
"docid": "361978",
"text": "I know that there are a lot service on the internet helping to form an LLC online with a fee around $49. Is it neccessarry to pay them to have an LLC or I can do that myself? No, you can do it yourself. The $49 is for your convenience, but there's nothing they can do that you wouldn't be able to do on your own. What I need to know and what I need to do before forming an LLC? You need to know that LLC is a legal structure that is designed to provide legal protections. As such, it is prudent to talk to a legal adviser, i.e.: a Virginia-licensed attorney. Is it possible if I hire some employees who living in India? Is the salary for my employees a expense? Do I need to claim this expense? This, I guess, is entirely unrelated to your questions about LLC. Yes, it is possible. The salary you pay your employees is your expense. You need to claim it, otherwise you'd be inflating your earnings which in certain circumstances may constitute fraud. What I need to do to protect my company? For physical protection, you'd probably hire a security guard. If you're talking about legal protections, then again - talk to a lawyer. What can I do to reduce taxes? Vote for a politician that promises to reduce taxes. Most of them never deliver though. Otherwise you can do what everyone else is doing - tax planning. That is - plan ahead your expenses, time your invoices and utilize tax deferral programs etc. Talk to your tax adviser, who should be a EA or a CPA licensed in Virginia. What I need to know after forming an LLC? You'll need to learn what are the filing requirements in your State (annual reports, tax reports, business taxes, sales taxes, payroll taxes, etc). Most are the same for same proprietors and LLCs, so you probably will not be adding to much extra red-tape. Your attorney and tax adviser will help you with this, but you can also research yourself on the Virginia department of corporations/State department (whichever deals with LLCs).",
"title": ""
},
{
"docid": "416268",
"text": "\"Did it show just your address, or was your name on it as well? You didn't share how long you've lived at the address either, so it makes me wonder whether a former tenant is the one who filed that paperwork. It's also possible that someone used your address when making a filing. Whether that was deliberate or accidental is hard to discern, as is their intent if it was intentional. It could be accidental -- someone picked \"\"CA\"\" for California when they meant to pick \"\"CO\"\" for Colorado or \"\"CT\"\" for Connecticut...These things do happen. It can't make you feel any better about the situation though. You should be able to go online to the California Secretary of State's website (here) and look up everything filed by the LLC with the state. That will show who the founders were and everything else that is a matter of public record on the LLC. At the very least, you can obtain the registered agent's name and address for the LLC, which you can then use to contact them and ask why your address is listed as the LLC's business address. Once you have that info, you can then contact the Secretary of State and tell them it isn't you so they can do whatever is necessary to correct this. This doesn't sound like a difficult matter to clear up, but it's important to do your homework first and gather as much information as you can before you call the state. Answering \"\"I don't know\"\" won't get you very far with them compared to having the best answers you can about where the mistake started. I hope this helps. Good luck!\"",
"title": ""
},
{
"docid": "123418",
"text": "\"(I answered a similar question before.) Essentially, you shouldn't trust a site you find on the Internet merely because it looks professional and real. Before signing up with any new service provider you found online, you should verify the authenticity of both the organization itself and their web site address. Even if the name displayed by a web site represents a legitimate brokerage firm, any site you happen to come across on the Internet could be an elaborate spoof of a real company, intended to capture your personal details (or worse). First, to check if a brokerage firm is in fact registered to trade securities – in the United States – you can consult FINRA's BrokerCheck online service. This might be the first of many checks you should undertake ... after you convince yourself that FINRA is legitimate. A meta-problem ;-) Then, if you want to know if the web site address is authentic, one way is to contact that broker offline using the contact information found from a trusted source, such as the FINRA BrokerCheck details. Unfortunately, those details do not currently appear to contain the broker's web site URL. (Else, that could be useful.) Another thing to look at is the site's login or sign-up page, for a valid SSL certificate that is both issued to the correct legal name of the brokerage firm as well as has been signed by a well-known certificate authority (e.g. VeriSign). For a financial services firm of any kind, you should look for and expect to see an Extended Validation Certificate. Any other kind of certificate might only assert that the certificate was issued to the domain-name owner, and not necessarily to an organization with the registered legal name. (Yes, anybody can register a domain with a similar name and then acquire a basic SSL certificate for that domain.) FWIW, Scottrade and ShareBuilder are both legitimate brokers (I was aware already of each, but I also just checked in the FINRA tool), and the URLs currently linked to by the question are legitimate web site addresses for each. Also, you can see their EV certificates in action on secured pages here and here. As to whether your investments with those brokers would be \"\"safe\"\" in the event of the broker failing (e.g. goes bankrupt), you'll want to know that they are members of the Securities Investor Protection Corporation (Wikipedia). (Of course, this kind of protection doesn't protect you if your investments simply go down in value.) But do your own due diligence – always.\"",
"title": ""
},
{
"docid": "341220",
"text": "\"No, there are no issues. When you form the corp in DE, you pick a business there to serve as your \"\"agent\"\" (essentially someone who knows to get in contact with you). The \"\"agent\"\" will notify you about taxes and any mail you get, but besides the fee they charge you for being the agent, you should file all the taxes directly with DE (franchise tax is easy to file on the web) instead of going through the agent and paying a surcharge. When your LLC files taxes, you'll do so in DE and then the LLC will issue you a federal and state K1. You'll file taxes where you reside and use the federal K1, but I think you might have to file DE state taxes (unsure about this part, feel free to edit or comment and I'll correct).\"",
"title": ""
},
{
"docid": "311947",
"text": "\"I'll answer in general terms, since I'm not familiar with the price ranges in Florida. The LLC formation costs $125 (state fee). In addition you'll need a registered agent. Registered agent could be your CPA/EA/bookkeeper/property manager/local friend, or you can pay firms specializing in providing registration and agents services such as NorthWestern or LegalZoom (there are many others). You'll need to pay an annual fee of ~$140 in Florida. If you are using someone to do the formation, they'll charge more (usually the on-line services are cheaper than a local CPA or attorney, by $100-$300). Bookkeeping will probably be charged by the hour, but some bookkeepers charge flat fees for small accounts. Per hour would be probably in the range of $40-$80. You'll have to pay taxes - both in Florida (where the property is) and on the Federal level to the IRS. You'll be paying them as a non-Resident individual. Your CPA/EA will charge you anywhere between $150 to $500 for that (if they charge more - run away, unless there's some specific complication that requires extra costs). You will need a ITIN for that, your CPA/EA can help you get one or you can apply yourself. Be careful with all those people selling cr@p about organizing in Delaware/Wyoming/Nevada (like CQM in his answer). Organizing in a state other than where the properties are located (or off-shore) won't save you a dime, and not only that - it will add to the costs. Because you'll have to pay to the state where you organized (CQM mentioned Wyoming - $50/year), keep registered agent in the state of organization (+$99) and also do all the things I've described above about Florida - as a \"\"Foreign\"\" (out of state) entity, which may mean higher fees. It won't save you any taxes as well, because you pay taxes to the state from which you derive income, which is Florida, either way. Remember that what you call LLC in Italy may be in fact a \"\"Corporation\"\" as defined in the US, and there's a huge difference. You should probably not put a real-estate property in a Corporation in the US. You must get a legal advice from a (Florida) lawyer ($0-$500/hr consultation), and a tax advice from a (Florida) CPA/EA ($0-$200/hr consultation). Do not consider anything I write here as a legal or tax advice, because it is not. You need a professional to help you because as an Italian, you don't know how things work exactly and relying on rumours and half-truths that you may find and get over the Internet may end up costing you significantly in damages. Also, talk to a reliable real estate agent and property manager before making any purchases.\"",
"title": ""
},
{
"docid": "1873",
"text": "\"I expect the company wanted to pay you for a product (on a purchase order) rather than as a contract laborer. Whatever. Would they be willing to re-issue the check to you as a sole proprietor of a business named ABC Consulting (or anything like that)? You can register your sole proprietor business with the state using a \"\"Doing Business As\"\" (DBA, or fictitious name), and then open the bank account for your business using the check provided by the customer as the first deposit. (There is likely a smaller registration fee for the DBA.) If they won't re-issue the check and you have to go the LLC route... Scrounge up $125 doing odd jobs or borrowing from a friend or parents. Seriously, anyone can earn that amount of money in a week or two. Besides the filing fee for the LLC, your bank may require you to provide an Operating Agreement (which is not required by the State). The Operating Agreement can be simple, or more complex if you have a partner (even if it's a spouse). If you do have a partner, it is essential to have such an agreement because it would specify the responsibilities and benefits allocated to each partner, particularly in the event of equity distributions (taking money out of the business, or liquidating and ending the LLC). There are websites that will provide you a boilerplate form for Operating Agreements. But if your business is anything more than just single member LLC, you should pay an attorney to draw one up for you so the wording is right. It's a safeguard against potential future lawsuits. And, while we're at it, don't forget to obtain a EIN (equivalent to a SSN) from the IRS for your LLC. There's no cost, but you'll have to have it to file taxes as a business for every year the LLC exists and has income. Good luck!\"",
"title": ""
},
{
"docid": "546329",
"text": "The LLC (not you) is probably in debt to the California FTB. Any LLC registered in California must pay at least $800 a year, until it is officially dissolved (i.e.: notice of cancellation/dissolution properly filed with the California Secretary of State). The FTB may come after members (including you) personally, if it can prove that the failure to pay was due to your negligence. Talk to a CA-licensed EA/CPA about how to resolve this. Otherwise, at least from what you've described, there were no other taxable events. LLC is a disregarded entity, so the IRS doesn't care about it much anyway (unless someone was stupid enough to elect it to be taxed as a corporation, that is). Keep in mind that when in doubt - you are always better off with a professional (a CPA/EA licensed in your State) advice.",
"title": ""
},
{
"docid": "509318",
"text": "You won't be able to avoid the $800 fee. CA FTB has a very specific example, which is identical to your situation (except that they use NV instead of AZ), to show that the LLC has liability in California. State of formation is of no matter, you'll just be liable for fees in that state in addition to the CA fees. This is in fact a very common situation (that's why they have this as an example to begin with). See CA FTB 568 booklet. The example is on page 14. I suggest forming the LLC in AZ/CA and registering it as a foreign entity in the other state (AZ if formed in CA, the better option IMHO, or CA if formed in AZ). You'll have tax liability in both the states, AZ taxes can be credited towards the CA taxes. Instead of forming LLC, you can cover your potential liability with sufficient insurance coverage.",
"title": ""
},
{
"docid": "349348",
"text": "\"I'm assuming that when you say \"\"convert to S-Corp tax treatment\"\" you're not talking about actually changing your LLC to a Corporation. There are two distinct pieces of the puzzle here. First, there's your organizational form. Your state, which is where the business is legally formed and recognized, creates the LLC or Corporation. \"\"S-Corp\"\" doesn't come into play here: your company is either an LLC or a Corporation. (There are a handful of other organizational types your state might have, e.g. PLLC, Limited Partnership, etc.; none of these are immediately relevant to this discussion). Second, there's the tax treatment you receive by the IRS. If your company was created by the state as an LLC, note that the IRS doesn't recognize LLCs as a distinct organizational type: you elect to be taxed as an individual (for single member LLCs), a partnership (for multiple member LLCs), or as a corporation. The former two elections are \"\"pass through\"\" -- there's no additional level of taxation on corporate profits, everything just passes through to the owners. The latter election introduces a tax on corporate profits. When you elect pass-through treatment, a single-member LLC files on Schedule C; a multiple-member LLC will prepare a form K-1 which you will include on your 1040. If your company was created by the state as a Corporation (not an LLC), you could still elect pass-through taxation if your company qualifies under the rules in Subchapter S (i.e. \"\"an S-Corp\"\"). States do not recognize \"\"S-Corp\"\" as part of the organizational process -- that's just a tax distinction used by the IRS (and possibly your state's tax authorities). In your case, if you are a single-member LLC (and assuming there are no other reasons to organize as a corporation), talking about \"\"S-Corp tax treatment\"\" doesn't make any sense. You'll just file your schedule C; in my experience it's fairly simple. (Note that this is based on my experience of single- and multiple-member LLCs in just two states. Your state may have different rules that affect state-level taxation; and the rules may change from year to year. I've found that hiring a good CPA to prepare the forms saves a good bit of stress and time that can be better applied to the business.)\"",
"title": ""
},
{
"docid": "107536",
"text": "Supposedly this also means that I am free from having to pay California corporate taxes? Not in the slightest. Since you (the corporate employee) reside in CA - the corporation is doing business in CA and is liable for CA taxes. Or, does this mean I am required to pay both CA taxes and Delaware fees? (In this case, minimal, just a paid agent from incorporate.com) I believe DE actually does have corporate taxes, check it out. But the bottom line is yes, you're liable for both CA and DE costs of doing corporate business (income taxes, registered agents, CA corp fee, etc). Is there any benefit at all for me to be a Delaware C-Corp or should I dissolve and start over. Or just re-incorporate as California LLC Unless you intend to go public anytime soon or raise money from VCs/investors - there's no benefit whatsoever in incorporating in DE. You should seek a legal advice with an attorney, of course, since benefits are legal issues (usually related to choosing jurisdiction for litigation etc). If you're a one-person freelancer, doing C-Corp was not the best decision as well. Tax-wise you'd be much better off with a S-Corp, or a LLC - both pass-through and have no (Federal) entity-level taxes. Corporate rates are generally higher than individual rates, and less deductions can be taken. In California, check with a CPA/EA licensed in the State, since both S-Corp and LLC would be taxed, and taxed differently.",
"title": ""
},
{
"docid": "535918",
"text": "\"What would be the best strategy to avoid paying income taxes on the sale after I move to another US state? Leaving the US and terminating your US residency before the sale closes. Otherwise consider checking your home country's tax treaty with the US. In any case, for proper tax planning you should employ a licensed tax adviser - an EA, CPA or an attorney licensed in your State (the one you'd be when the sale closes). No-one else is legally allowed to provide you tax advice on the matter. Because the company abroad is befriended, I have control over when (and e.g. in how many chunks) the earnings of the sale flow into my LLC. So I can plan where I live when that money hits my US account. I'm not familiar with the term \"\"befriended\"\" in this context, but form what I understand your description - its a shell corporation under your own control. This means that the transfer of money between the corporation and your LLC is of no consequence, you constructively received the money when the corporation got it, not the LLC. Your fundamental misunderstanding is that there's importance to when the money hits your US bank account. This is irrelevant. The US taxes your worldwide income, so it is taxed when you earn it, not when you transfer it into the country (as opposed to some other countries, for example India or the UK). As such, in your current scheme, it seems to me that you're breaking the US tax law. This is my personal impression, of course, get a professional advice from a licensed tax professional as I defined earlier.\"",
"title": ""
},
{
"docid": "121393",
"text": "\"I work in the legal services industry, selling these products for a competitor of theirs who shall remain nameless. The LLC filing itself in most cases is a simple fill in the blank form. You can likely file yourself either online or through the mail, depending on the state. Only a handful require an original document. You can apply for the EIN for free on the IRS website and usually have it within a few minutes. If you already have someone assisting with your annual LLC taxes you wouldn't need their services for that either. If their compliance kit involves any business licensing research, it may be worthwhile - but you can also order those services a la carte from vendors like LLX and BusinessLicenses.com. What you're really paying for is the registered agent service - the address for public record with the state so they know where to send any service of process - and you're paying for the convenience of a \"\"one stop shop\"\" instead of handling all the legwork yourself.\"",
"title": ""
},
{
"docid": "315086",
"text": "Is the business an S-Corp, LLC or Sole Prop? I am going to guess based on the question that it is an LLC that you never closed with the state and you live in a state (NY) that charges a fee for having an LLC in the state in which case you owe those fees to the state. I am not aware of any taxes on the mere existence of a business by the IRS. I think you are going to find out that the are no taxes owed to the IRS for this nonexistent activity.",
"title": ""
},
{
"docid": "330622",
"text": "Delaware LLC requires that each business entity have and hold an enterprise Registered in the State of Delaware who can be both a character resident or enterprise entity this is legal to do business in the Wilmington, Delaware. the Delaware LLC has offered the same asset protections and tax advantages that a corporation offers. Often the LLC is the simpler, more flexible choice for small businesses. This small amount of required information not only makes it easy to start an LLC in Delaware, but it also helps to keep your identity and personal information secure.",
"title": ""
}
] |
791
|
Migraine with aura is associated with ischemic stroke.
|
[
{
"docid": "15984735",
"text": "OBJECTIVE To evaluate the association between migraine and cardiovascular disease, including stroke, myocardial infarction, and death due to cardiovascular disease. DESIGN Systematic review and meta-analysis. DATA SOURCES Electronic databases (PubMed, Embase, Cochrane Library) and reference lists of included studies and reviews published until January 2009. Selection criteria Case-control and cohort studies investigating the association between any migraine or specific migraine subtypes and cardiovascular disease. Review methods Two investigators independently assessed eligibility of identified studies in a two step approach. Disagreements were resolved by consensus. Studies were grouped according to a priori categories on migraine and cardiovascular disease. DATA EXTRACTION Two investigators extracted data. Pooled relative risks and 95% confidence intervals were calculated. RESULTS Studies were heterogeneous for participant characteristics and definition of cardiovascular disease. Nine studies investigated the association between any migraine and ischaemic stroke (pooled relative risk 1.73, 95% confidence interval 1.31 to 2.29). Additional analyses indicated a significantly higher risk among people who had migraine with aura (2.16, 1.53 to 3.03) compared with people who had migraine without aura (1.23, 0.90 to 1.69; meta-regression for aura status P=0.02). Furthermore, results suggested a greater risk among women (2.08, 1.13 to 3.84) compared with men (1.37, 0.89 to 2.11). Age less than 45 years, smoking, and oral contraceptive use further increased the risk. Eight studies investigated the association between migraine and myocardial infarction (1.12, 0.95 to 1.32) and five between migraine and death due to cardiovascular disease (1.03, 0.79 to 1.34). Only one study investigated the association between women who had migraine with aura and myocardial infarction and death due to cardiovascular disease, showing a twofold increased risk. CONCLUSION Migraine is associated with a twofold increased risk of ischaemic stroke, which is only apparent among people who have migraine with aura. Our results also suggest a higher risk among women and risk was further magnified for people with migraine who were aged less than 45, smokers, and women who used oral contraceptives. We did not find an overall association between any migraine and myocardial infarction or death due to cardiovascular disease. Too few studies are available to reliably evaluate the impact of modifying factors, such as migraine aura, on these associations.",
"title": "Migraine and cardiovascular disease: systematic review and meta-analysis."
}
] |
[
{
"docid": "23785605",
"text": "BACKGROUND Migraine, particularly with aura, is a risk factor for early-onset ischemic stroke. The underlying mechanisms are unknown, but may in part be due to migraineurs having an increased risk profile for cardiovascular disease. In this study, the authors compare the cardiovascular risk profile of adult migraineurs to that of nonmigraineurs. METHODS Participants (n = 5,755, 48% men, age 20 to 65 years) are from the Genetic Epidemiology of Migraine (GEM) study, a population-based study in the Netherlands. A total of 620 current migraineurs were identified: 31% with aura (MA), 64% without aura (MO), and 5% unclassified. Controls were 5,135 individuals without lifetime migraine. Measured cardiovascular risk factors included blood pressure (BP), serum total and high-density lipoprotein cholesterol (TC, HDL), smoking, oral contraceptive use, and the Framingham risk score for myocardial infarction or coronary heart disease (CHD) death. RESULTS Compared to controls, migraineurs were more likely to smoke (OR = 1.43 [1.1 to 1.8]), less likely to consume alcohol (OR = 0.58 [0.5 to 0.7]), and more likely to report a parental history of early myocardial infarction. Migraineurs with aura were more likely to have an unfavorable cholesterol profile (TC > or = 240 mg/dL [OR = 1.43 (0.97 to 2.1)], TC:HDL ratio > 5.0 [OR = 1.64 (1.1 to 2.4)]), have elevated BP (systolic BP > 140 mm Hg or diastolic BP > 90 mm Hg [OR = 1.76 (1.04 to 3.0)]), and report a history of early onset CHD or stroke (OR = 3.96 [1.1 to 14.3]); female migraineurs with aura were more likely to be using oral contraceptives (OR = 2.06 [1.05 to 4.0]). The odds of having an elevated Framingham risk score for CHD were approximately doubled for the migraineurs with aura. CONCLUSIONS Migraineurs, particularly with aura, have a higher cardiovascular risk profile than individuals without migraine.",
"title": "Cardiovascular risk factors and migraine: the GEM population-based study."
},
{
"docid": "14566771",
"text": "The relationship of migraine and stroke is complex. Stroke may be coincidental with migraine but migraine may confer an increased risk of stroke in women under 45 years of age and possibly in men who have migraine with aura. Stroke may mimic migraine but migraine syndromes may be symptomatic of underlying cerebrovascular disorders. True migraine-induced stroke is rare. The mechanisms of stroke induced during a migraine attack remain to be determined but probably involve an interaction between the dynamic shifts in cerebral blood flow and stroke risk factors.",
"title": "Stroke and migraine--the spectrum of cause and effect."
},
{
"docid": "8672737",
"text": "BACKGROUND AND PURPOSE Migraineurs are at increased risk of cerebellar infarcts and supratentorial white matter lesions. The prevalence, frequency, and distribution of infratentorial hyperintense lesions in migraine are unknown. METHODS Migraineurs with aura (n=161), without aura (n=134), and controls (n=140) from a population-based sample of adults (30 to 60 years of age) were evaluated with MRI. RESULTS Infratentorial hyperintensities were identified in 13 of 295 (4.4%) migraineurs and in 1 of 140 (0.7%) controls (P=0.04). Twelve cases had hyperintensities, mostly bilaterally, in the dorsal basis pontis. Those with infratentorial hyperintensities also had supratentorial white matter lesions more often. CONCLUSIONS We found an increased prevalence of infratentorial (mostly pontine) hyperintensities in migraineurs from the general population. This extends the knowledge about vulnerable brain regions and type of lesions in migraine brains. A hemodynamic ischemic pathogenesis is likely, but further research is needed.",
"title": "Brain stem and cerebellar hyperintense lesions in migraine."
},
{
"docid": "14726759",
"text": "BACKGROUND AND PURPOSE There are only few small studies assessing potential risk factors, comorbidity, and prognostic factors in adult spontaneous cervicocerebral artery dissection (CAD). METHODS We conducted a retrospective, hospital-based analysis on the prognostic factors and association of CAD with vascular risk factors in 301 consecutive Finnish patients, diagnosed from 1994 to 2007. RESULTS Two thirds of the patients were men (68%). Women were younger than men. Migraine (36% of all patients), especially with visual aura (63% of all migraineurs), and smoking were more common in patients with CAD compared with the general Finnish population. At 3 months, 247 (83%) patients reached a favorable outcome. Occlusion of the dissected artery, internal carotid artery dissection (ICAD), and recent infection in infarction patients were associated with a poorer outcome. ICAD patients had less often brain infarction, but the strokes they had were more severe. Seven (2.3%) patients died during the follow-up (mean 4.0 years, 1186 patient years). Six (2%) patients had verified CAD recurrence. CONCLUSIONS This study provides evidence for the association of CAD with male sex, and possible association with smoking and migraine. Occlusion of the dissected artery, ICAD, and infection appear to be associated with poorer outcome.",
"title": "Adult cervicocerebral artery dissection: a single-center study of 301 Finnish patients."
},
{
"docid": "38369817",
"text": "BACKGROUND Transcranial contrast Doppler studies have shown an increased prevalence of right-to-left shunts in patients with migraine with aura compared with controls. The anatomy and size of these right-to-left shunts have never been directly assessed. METHODS In a cross-sectional case-control study, the authors performed transesophageal contrast echocardiography in 93 consecutive patients with migraine with aura and 93 healthy controls. RESULTS A patent foramen ovale was present in 44 (47% [95% CI 37 to 58%]) patients with migraine with aura and 16 (17% [95% CI 10 to 26%]) control subjects (OR 4.56 [95% CI 1.97 to 10.57]; p < 0.001). A small shunt was equally prevalent in migraineurs (10% [95% CI 5 to 18%]) and controls (10% [95% CI 5 to 18%]), but a moderate-sized or large shunt was found more often in the migraine group (38% [95% CI 28 to 48%] vs 8% [95% CI 2 to 13%] in controls; p < 0.001). The presence of more than a small shunt increased the odds of having migraine with aura 7.78-fold (95% CI 2.53 to 29.30; p < 0.001). Besides patent foramen ovale prevalence and shunt size, no other echocardiographic differences were found between the study groups. Headache and baseline characteristics did not differ in migraine patients with and without shunt. CONCLUSIONS Nearly half of all patients with migraine with aura have a right-to-left shunt due to a patent foramen ovale. Shunt size is larger in migraineurs than controls. The clinical presentation of migraine is identical in patients with and without a patent foramen ovale.",
"title": "Prevalence and size of directly detected patent foramen ovale in migraine with aura."
},
{
"docid": "17930286",
"text": "OBJECTIVE To evaluate the association of overall and specific headaches with volume of white matter hyperintensities, brain infarcts, and cognition. DESIGN Population based, cross sectional study. SETTING Epidemiology of Vascular Ageing study, Nantes, France. PARTICIPANTS 780 participants (mean age 69, 58.5% women) with detailed headache assessment. MAIN OUTCOME MEASURES Brain scans were evaluated for volume of white matter hyperintensities (by fully automated imaging processing) and for classification of infarcts (by visual reading with a standardised assessment grid). Cognitive function was assessed by a battery of tests including the mini-mental state examination. RESULTS 163 (20.9%) participants reported a history of severe headache and 116 had migraine, of whom 17 (14.7%) reported aura symptoms. An association was found between any history of severe headache and increasing volume of white matter hyperintensities. The adjusted odds ratio of being in the highest third for total volume of white matter hyperintensities was 2.0 (95% confidence interval 1.3 to 3.1, P for trend 0.002) for participants with any history of severe headache when compared with participants without severe headache being in the lowest third. The association pattern was similar for all headache types. Migraine with aura was the only headache type strongly associated with volume of deep white matter hyperintensities (highest third odds ratio 12.4, 1.6 to 99.4, P for trend 0.005) and with brain infarcts (3.4, 1.2 to 9.3). The location of infarcts was predominantly outside the cerebellum and brain stem. Evidence was lacking for cognitive impairment for any headache type with or without brain lesions. CONCLUSIONS In this population based study, any history of severe headache was associated with an increased volume of white matter hyperintensities. Migraine with aura was the only headache type associated with brain infarcts. Evidence that headache of any type by itself or in combination with brain lesions was associated with cognitive impairment was lacking.",
"title": "Headache, migraine, and structural brain lesions and function: population based Epidemiology of Vascular Ageing-MRI study"
},
{
"docid": "24148722",
"text": "OBJECTIVE The aim of this study was to investigate the possible microstructural abnormalities of the corpus callosum (CC) in adult patients with migraine without aura complicated with depressive/anxious disorder. BACKGROUND Emotional disorders, especially depression and anxiety, are with relatively higher incidence in migraine population. However, the mechanism of migraine complicated with depressive/anxious disorder remains unclear. METHODS Diffusion tensor magnetic resonance imaging was carried out in 12 adult patients with simple migraine (without aura and without depressive/anxious disorder) (S-M group), 12 adult patients with complicated migraine (without aura but complicated with depressive/anxious disorder) (Co-M group), and 12 age- and sex-matched healthy subjects (Control group). Fractional anisotropy (FA) and apparent diffusion coefficient were measured at genu, body, and splenium of the CC, respectively. RESULTS There were significant differences in FA values at all locations of the CC among the 3 groups. The FA values from both the SM and Co-M groups were significantly lower than the control (P < .05 and P < .01, respectively). The FA values from Co-M group were significantly lower than the SM group (P < .01). The apparent diffusion coefficient values of the above regions had no significant differences among these groups (P > .05). There were negative correlations between FA value of genu of the CC and disease course as well as FA value of genu and body of the CC and headache frequency (P < .05). Negative correlations were also found between FA values at all locations of the CC and Hamilton anxiety and Hamilton depression scores (both P < .05). CONCLUSIONS There might be an integrity change of neurofibrotic microstructures existing as a possible neuroanatomical basis in the CC of migraine patients complicated with depressive/anxious disorder.",
"title": "A diffusion tensor magnetic resonance imaging study of corpus callosum from adult patients with migraine complicated with depressive/anxious disorder."
},
{
"docid": "23627419",
"text": "RATIONALE Although obstructive sleep apnea is associated with physiological perturbations that increase risk of hypertension and are proatherogenic, it is uncertain whether sleep apnea is associated with increased stroke risk in the general population. OBJECTIVES To quantify the incidence of ischemic stroke with sleep apnea in a community-based sample of men and women across a wide range of sleep apnea. METHODS Baseline polysomnography was performed between 1995 and 1998 in a longitudinal cohort study. The primary exposure was the obstructive apnea-hypopnea index (OAHI) and outcome was incident ischemic stroke. MEASUREMENTS AND MAIN RESULTS A total of 5,422 participants without a history of stroke at the baseline examination and untreated for sleep apnea were followed for a median of 8.7 years. One hundred ninety-three ischemic strokes were observed. In covariate-adjusted Cox proportional hazard models, a significant positive association between ischemic stroke and OAHI was observed in men (P value for linear trend: P = 0.016). Men in the highest OAHI quartile (>19) had an adjusted hazard ratio of 2.86 (95% confidence interval, 1.1-7.4). In the mild to moderate range (OAHI, 5-25), each one-unit increase in OAHI in men was estimated to increase stroke risk by 6% (95% confidence interval, 2-10%). In women, stroke was not significantly associated with OAHI quartiles, but increased risk was observed at an OAHI greater than 25. CONCLUSIONS The strong adjusted association between ischemic stroke and OAHI in community-dwelling men with mild to moderate sleep apnea suggests that this is an appropriate target for future stroke prevention trials.",
"title": "Obstructive sleep apnea-hypopnea and incident stroke: the sleep heart health study."
},
{
"docid": "37065914",
"text": "BACKGROUND AND PURPOSE Soluble corin was decreased in coronary heart disease. Given the connections between cardiac dysfunction and stroke, circulating corin might be a candidate marker of stroke risk. However, the association between circulating corin and stroke has not yet been studied in humans. Here, we aimed to examine the association in patients wtith stroke and community-based healthy controls. METHODS Four hundred eighty-one patients with ischemic stroke, 116 patients with hemorrhagic stroke, and 2498 healthy controls were studied. Serum soluble corin and some conventional risk factors of stroke were examined. Because circulating corin was reported to be varied between men and women, the association between serum soluble corin and stroke was evaluated in men and women, respectively. RESULTS Patients with ischemic and hemorrhagic stroke had a significantly lower level of serum soluble corin than healthy controls in men and women (all P values, <0.05). In multivariate analysis, men in the lowest quartile of serum soluble corin were more likely to have ischemic (odds ratio [OR], 4.90; 95% confidence interval, 2.99-8.03) and hemorrhagic (OR, 17.57; 95% confidence interval, 4.85-63.71) stroke than men in the highest quartile. Women in the lowest quartile of serum soluble corin were also more likely to have ischemic (OR, 3.10; 95% confidence interval, 1.76-5.44) and hemorrhagic (OR, 8.54; 95% confidence interval, 2.35-31.02) stroke than women in the highest quartile. ORs of ischemic and hemorrhagic stroke were significantly increased with the decreasing levels of serum soluble corin in men and women (all P values for trend, <0.001). CONCLUSIONS Serum soluble corin was decreased in patients with stroke compared with healthy controls. Our findings raise the possibility that serum soluble corin may have a pathogenic role in stroke.",
"title": "Serum Soluble Corin is Decreased in Stroke."
},
{
"docid": "39390206",
"text": "OBJECTIVE To measure in vivo, using diffusion tensor magnetic resonance imaging (DT-MRI) the extent of pathological damage of normal appearing brain tissue (NABT) from patients with migraine. METHODS Dual echo and DT-MRI scans of the brain were acquired from 34 patients with migraine and 17 sex and age matched healthy volunteers. Mean diffusivity (MD) and fractional anisotropy (FA) histograms of the NABT were obtained from all subjects and the histograms' peak heights and average NABT MD and FA measured. When present, average MD and FA values of T2 visible lesions were also measured. RESULTS In comparison with healthy volunteers, patients with migraine had lower MD histogram peak height (p=0.02) of the NABT. No differences were found in FA histogram derived metrics between migraine patients and healthy subjects. No difference was found for any MD and FA histogram derived metrics between migraine patients with and without brain MRI lesions, and between patients with and without aura. CONCLUSIONS This study shows that, although brain damage may extend beyond T2 weighted abnormalities in patients with migraine, the severity of these \"occult\" changes is mild compared with that found in other diseases associated with white matter abnormality.",
"title": "A diffusion tensor magnetic resonance imaging study of brain tissue from patients with migraine."
},
{
"docid": "32328114",
"text": "Stroke ranks as the third leading cause of death in the United States. It is now estimated that there are more than 700 000 incident strokes annually and 4.4 million stroke survivors.1 2 The economic burden of stroke was estimated by the American Heart Association to be $51 billion (direct and indirect costs) in 1999.3 Despite the advent of treatment of selected patients with acute ischemic stroke with tissue plasminogen activator and the promise of other experimental therapies, the best approach to reducing the burden of stroke remains prevention.4 5 High-risk or stroke-prone individuals can be identified and targeted for specific interventions.6 This is important because epidemiological data suggest a substantial leveling off of prior declines in stroke-related mortality and a possible increase in stroke incidence.7 8 The Stroke Council of the American Heart Association formed an ad hoc writing group to provide a clear and concise overview of the evidence regarding various established and potential stroke risk factors. The writing group was chosen based on expertise in specific subject areas, and it used literature review, reference to previously published guidelines, and expert opinion to summarize existing evidence and formulate recommendations (Table 1⇓). View this table: Table 1. Levels of Evidence and Grading of Recommendations As given in Tables 2 through 4⇓⇓⇓, risk factors or risk markers for a first stroke were classified according to potential for modification (nonmodifiable, modifiable, or potentially modifiable) and strength of evidence (well documented, less well documented).5 The tables give the estimated prevalence, population attributable risk, relative risk, and risk reduction with treatment for each factor when known. Population attributable risk reflects the proportion of ischemic strokes in the population that can be attributed to a particular risk factor and is given by the formula 100×[prevalence(relative risk−1)/prevalence(relative risk−1)+1]). …",
"title": "Primary prevention of ischemic stroke: A statement for healthcare professionals from the Stroke Council of the American Heart Association."
},
{
"docid": "43647194",
"text": "The availability of valid migraine-specific questionnaires is important when large numbers of migraine patients have to be analysed. The Finnish Migraine-Specific Questionnaire has been validated in two stages. In the first, a clinical diagnosis of migraine was reached, using International Headache Society criteria, in 100 consecutive patients. Migraine was then diagnosed independently on the basis of responses to the Finnish Migraine-Specific Questionnaire. In the second stage, responses to 100 questionnaires returned consecutively in a family study in progress were analysed, and respondents were contacted by telephone for interview and diagnosis of migraine. Contact proved impossible in six cases. The sensitivity of the questionnaire for migraine was 0.99 (167 out of 168; validation stages 1 and 2 combined) and specificity was 0.96 (25 out of 26 cases; validation stage 2). It also proved possible to differentiate between migraine with and without aura on the basis of responses to the Finnish Migraine-Specific Questionnaire: chance-corrected agreement (Cohen's kappa) was 0.804 in relation to diagnoses reached on the basis of responses to the Finnish Migraine-Specific Questionnaire and clinically was 0.858 in relation to diagnoses reached on the basis of responses to the Finnish Migraine-Specific Questionnaire combined with the results of the telephone interviews. A value for Cohen's kappa > 0.75 indicates good agreement. Therefore, use of the Finnish Migraine-Specific Questionnaire in research into migraine genetics is justified.",
"title": "Validation of a migraine-specific questionnaire for use in family studies."
},
{
"docid": "18256197",
"text": "BACKGROUND AND PURPOSE The level of total homocysteine (tHcy) that confers a risk of ischemic stroke is unsettled, and no prospective cohort studies have included sufficient elderly minority subjects. We investigated the association between mild to moderate fasting tHcy level and the incidence of ischemic stroke, myocardial infarction, and vascular death in a multiethnic prospective study. METHODS A population-based cohort was followed for vascular events (stroke, myocardial infarction, and vascular death). Baseline values of tHcy and methylmalonic acid were measured among 2939 subjects (mean age, 69+/-10; 61% women, 53% Hispanics, 24% blacks, and 20% whites). Cox proportional models were used to calculate hazard ratios (HRs) and 95% CIs in tHcy categories after adjusting for age, race, education, renal insufficiency, B12 deficiency, and other risk factors. RESULTS The adjusted HR for a tHcy level > or =15 micromol/L compared with <10 micromol/L was greatest for vascular death (HR=6.04; 95% CI, 3.44 to 10.60), followed by combined vascular events (HR=2.27; 95% CI, 1.51 to 3.43), ischemic stroke (HR=2.01; 95% CI, 1.00 to 4.05), and nonvascular death (HR=2.02; 95% CI, 1.31 to 3.14). Mild to moderate elevations of tHcy of 10 to 15 micromol/L were not significantly predictive of ischemic stroke, but increased the risk of vascular death (2.27; 95% CI, 1.44 to 3.60) and combined vascular events (1.42; 95% CI, 1.06 to 1.88). The effect of tHcy was stronger among whites and Hispanics, but not a significant risk factor for blacks. CONCLUSIONS Total Hcy elevations above 15 micromol/L are an independent risk factor for ischemic stroke, whereas mild elevations of tHcy of 10 to 15 micromol/L are less predictive. The vascular effects of tHcy are greatest among whites and Hispanics, and less among blacks.",
"title": "Homocysteine and the risk of ischemic stroke in a triethnic cohort: the NOrthern MAnhattan Study."
},
{
"docid": "21571708",
"text": "CONTEXT Circulating concentration of lipoprotein(a) (Lp[a]), a large glycoprotein attached to a low-density lipoprotein-like particle, may be associated with risk of coronary heart disease (CHD) and stroke. OBJECTIVE To assess the relationship of Lp(a) concentration with risk of major vascular and nonvascular outcomes. STUDY SELECTION Long-term prospective studies that recorded Lp(a) concentration and subsequent major vascular morbidity and/or cause-specific mortality published between January 1970 and March 2009 were identified through electronic searches of MEDLINE and other databases, manual searches of reference lists, and discussion with collaborators. DATA EXTRACTION Individual records were provided for each of 126,634 participants in 36 prospective studies. During 1.3 million person-years of follow-up, 22,076 first-ever fatal or nonfatal vascular disease outcomes or nonvascular deaths were recorded, including 9336 CHD outcomes, 1903 ischemic strokes, 338 hemorrhagic strokes, 751 unclassified strokes, 1091 other vascular deaths, 8114 nonvascular deaths, and 242 deaths of unknown cause. Within-study regression analyses were adjusted for within-person variation and combined using meta-analysis. Analyses excluded participants with known preexisting CHD or stroke at baseline. DATA SYNTHESIS Lipoprotein(a) concentration was weakly correlated with several conventional vascular risk factors and it was highly consistent within individuals over several years. Associations of Lp(a) with CHD risk were broadly continuous in shape. In the 24 cohort studies, the rates of CHD in the top and bottom thirds of baseline Lp(a) distributions, respectively, were 5.6 (95% confidence interval [CI], 5.4-5.9) per 1000 person-years and 4.4 (95% CI, 4.2-4.6) per 1000 person-years. The risk ratio for CHD, adjusted for age and sex only, was 1.16 (95% CI, 1.11-1.22) per 3.5-fold higher usual Lp(a) concentration (ie, per 1 SD), and it was 1.13 (95% CI, 1.09-1.18) following further adjustment for lipids and other conventional risk factors. The corresponding adjusted risk ratios were 1.10 (95% CI, 1.02-1.18) for ischemic stroke, 1.01 (95% CI, 0.98-1.05) for the aggregate of nonvascular mortality, 1.00 (95% CI, 0.97-1.04) for cancer deaths, and 1.00 (95% CI, 0.95-1.06) for nonvascular deaths other than cancer. CONCLUSION Under a wide range of circumstances, there are continuous, independent, and modest associations of Lp(a) concentration with risk of CHD and stroke that appear exclusive to vascular outcomes.",
"title": "Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality."
},
{
"docid": "24510595",
"text": "PURPOSE Patients with daily or near-daily headaches are commonly seen in neurology practices and in headache subspecialty centers, but there is little information on the prevalence of this condition in the general population. We present the first US-based study describing the prevalence and characteristics of frequent headache in the general population. METHODS In Baltimore County, Maryland, 13 343 individuals 18 to 65 years of age were selected by random-digit dialing and interviewed by telephone about their headaches. Subjects reporting 180 or more headaches per year were classified as having frequent headache. Three mutually exclusive subtypes of frequent headache were identified: frequent headache with migrainous features, chronic tension-type headache, and unclassified frequent headache. RESULTS The overall prevalence of frequent headache was 4.1% (5.0% female, 2.8% male; 1.8:1 female to male ratio). Frequent headache was 33% more common in Caucasians (4.4%) than in African Americans (3.3%). In both males and females, prevalence was highest in the lowest educational category. Among frequent headache sufferers, more than half (52% female, 56% male) met criteria for chronic tension-type headache, almost one third (33% female, 25% male) met criteria for frequent headache with migrainous features, and the remainder (15% female, 19% male) were unclassified. Overall, 30% of female and 25% of male frequent headache sufferers met International Headache Society (IHS) criteria for migraine (with or without aura). CONCLUSIONS Frequent headache is common in the general population and is more prevalent in Caucasians and in those with less than a high school education. Chronic tension-type headache is more common than frequent headache with migrainous features, though the latter is more disabling. Although more common in females than males, the female preponderance of frequent headache is less marked than in migraine. The sex ratio varies by frequent headache subtype.",
"title": "Prevalence of frequent headache in a population sample."
},
{
"docid": "16760369",
"text": "CONTEXT Clinicians and trialists have difficulty with identifying which patients are highest risk for cardiovascular events. Prior ischemic events, polyvascular disease, and diabetes mellitus have all been identified as predictors of ischemic events, but their comparative contributions to future risk remain unclear. OBJECTIVE To categorize the risk of cardiovascular events in stable outpatients with various initial manifestations of atherothrombosis using simple clinical descriptors. DESIGN, SETTING, AND PATIENTS Outpatients with coronary artery disease, cerebrovascular disease, or peripheral arterial disease or with multiple risk factors for atherothrombosis were enrolled in the global Reduction of Atherothrombosis for Continued Health (REACH) Registry and were followed up for as long as 4 years. Patients from 3647 centers in 29 countries were enrolled between 2003 and 2004 and followed up until 2008. Final database lock was in April 2009. MAIN OUTCOME MEASURES Rates of cardiovascular death, myocardial infarction, and stroke. RESULTS A total of 45,227 patients with baseline data were included in this 4-year analysis. During the follow-up period, a total of 5481 patients experienced at least 1 event, including 2315 with cardiovascular death, 1228 with myocardial infarction, 1898 with stroke, and 40 with both a myocardial infarction and stroke on the same day. Among patients with atherothrombosis, those with a prior history of ischemic events at baseline (n = 21,890) had the highest rate of subsequent ischemic events (18.3%; 95% confidence interval [CI], 17.4%-19.1%); patients with stable coronary, cerebrovascular, or peripheral artery disease (n = 15,264) had a lower risk (12.2%; 95% CI, 11.4%-12.9%); and patients without established atherothrombosis but with risk factors only (n = 8073) had the lowest risk (9.1%; 95% CI, 8.3%-9.9%) (P < .001 for all comparisons). In addition, in multivariable modeling, the presence of diabetes (hazard ratio [HR], 1.44; 95% CI, 1.36-1.53; P < .001), an ischemic event in the previous year (HR, 1.71; 95% CI, 1.57-1.85; P < .001), and polyvascular disease (HR, 1.99; 95% CI, 1.78-2.24; P < .001) each were associated with a significantly higher risk of the primary end point. CONCLUSION Clinical descriptors can assist clinicians in identifying high-risk patients within the broad range of risk for outpatients with atherothrombosis.",
"title": "Comparative determinants of 4-year cardiovascular event rates in stable outpatients at risk of or with atherothrombosis."
},
{
"docid": "3761017",
"text": "BACKGROUND Metformin, a widely used hypoglycemic drug, reduces stroke incidence and alleviates chronic inflammation in clinical trials. However, the effect of metformin in ischemic stroke is unclear. Here, we investigated the effect of metformin on ischemic stroke in mice and further explored the possible underlying mechanisms. METHODS Ninety-eight adult male CD-1 mice underwent 90-minute transient middle cerebral artery occlusion (tMCAO). Metformin (200 mg/kg) was administrated for up to 14 days. Neurobehavioral outcomes, brain infarct volume, inflammatory factors, blood-brain barrier (BBB) permeability and AMPK signaling pathways were evaluated following tMCAO. Oxygen glucose deprivation was performed on bEND.3 cells to explore the mechanisms of metformin in inhibiting inflammatory signaling pathways. RESULTS Infarct volume was reduced in metformin-treated mice compared to the control group following tMCAO (P < 0.05). Neurobehavioral outcomes were greatly improved in metformin-treated mice (P < 0.05). MPO+ cells, Gr1+ cells, MPO activity and BBB permeability were decreased after metformin administration (P < 0.05). In addition, metformin activated AMPK phosphorylation, inhibited NF-κB activation, down-regulated cytokine (IL-1β, IL-6, TNF-α) and ICAM-1 expression following tMCAO (P < 0.05). Furthermore, metformin activated AMPK signaling pathway and alleviated oxygen-glucose deprivation-induced ICAM-1 expression in bEND.3 cells (P < 0.05). Compound C, a selective AMPK inhibitor, eliminated this promotional effect. CONCLUSIONS Metformin down-regulated ICAM-1 in an AMPK-dependent manner, which could effectively prevent ischemia-induced brain injury by alleviating neutrophil infiltration, suggesting that metformin is a promising therapeutic agent in stroke therapy.",
"title": "Metformin attenuates blood-brain barrier disruption in mice following middle cerebral artery occlusion"
},
{
"docid": "7157436",
"text": "In the adult brain, new neurons are continuously generated in the subventricular zone and dentate gyrus, but it is unknown whether these neurons can replace those lost following damage or disease. Here we show that stroke, caused by transient middle cerebral artery occlusion in adult rats, leads to a marked increase of cell proliferation in the subventricular zone. Stroke-generated new neurons, as well as neuroblasts probably already formed before the insult, migrate into the severely damaged area of the striatum, where they express markers of developing and mature, striatal medium-sized spiny neurons. Thus, stroke induces differentiation of new neurons into the phenotype of most of the neurons destroyed by the ischemic lesion. Here we show that the adult brain has the capacity for self-repair after insults causing extensive neuronal death. If the new neurons are functional and their formation can be stimulated, a novel therapeutic strategy might be developed for stroke in humans.",
"title": "Neuronal replacement from endogenous precursors in the adult brain after stroke"
},
{
"docid": "23983289",
"text": "OBJECTIVES We sought to determine which ICD-9-CM codes in Medicare Part A data identify cardiovascular and stroke risk factors. DESIGN AND PARTICIPANTS This was a cross-sectional study comparing ICD-9-CM data to structured medical record review from 23,657 Medicare beneficiaries aged 20 to 105 years who had atrial fibrillation. MEASUREMENTS Quality improvement organizations used standardized abstraction instruments to determine the presence of 9 cardiovascular and stroke risk factors. Using the chart abstractions as the gold standard, we assessed the accuracy of ICD-9-CM codes to identify these risk factors. MAIN RESULTS ICD-9-CM codes for all risk factors had high specificity (>0.95) and low sensitivity (< or =0.76). The positive predictive values were greater than 0.95 for 5 common, chronic risk factors-coronary artery disease, stroke/transient ischemic attack, heart failure, diabetes, and hypertension. The sixth common risk factor, valvular heart disease, had a positive predictive value of 0.93. For all 6 common risk factors, negative predictive values ranged from 0.52 to 0.91. The rare risk factors-arterial peripheral embolus, intracranial hemorrhage, and deep venous thrombosis-had high negative predictive value (> or =0.98) but moderate positive predictive values (range, 0.54-0.77) in this population. CONCLUSIONS Using ICD-9-CM codes alone, heart failure, coronary artery disease, diabetes, hypertension, and stroke can be ruled in but not necessarily ruled out. Where feasible, review of additional data (eg, physician notes or imaging studies) should be used to confirm the diagnosis of valvular disease, arterial peripheral embolus, intracranial hemorrhage, and deep venous thrombosis.",
"title": "Accuracy of ICD-9-CM codes for identifying cardiovascular and stroke risk factors."
},
{
"docid": "6158879",
"text": "BACKGROUND Patients with diabetes mellitus (DM) are at high risk for recurrent cardiovascular events after acute coronary syndromes, in part because of increased platelet reactivity. The Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial Infarction 38 (TRITON-TIMI 38) showed an overall reduction in ischemic events with more intensive antiplatelet therapy with prasugrel than with clopidogrel but with more bleeding. We compared prasugrel with clopidogrel among subjects with DM in TRITON-TIMI 38. METHODS AND RESULTS We classified 13 608 subjects on the basis of preexisting history of DM and further according to insulin use. Prespecified analyses of the primary (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) and key secondary end points, including net clinical benefit (death, nonfatal myocardial infarction, nonfatal stroke, and nonfatal TIMI major bleeding) were compared by use of the log-rank test. We found that 3146 subjects had a preexisting history of DM, including 776 receiving insulin. The primary end point was reduced significantly with prasugrel among subjects without DM (9.2% versus 10.6%; hazard ratio [HR], 0.86; P=0.02) and with DM (12.2% versus 17.0%; HR, 0.70; P<0.001, P(interaction)=0.09). A benefit for prasugrel was observed among DM subjects on insulin (14.3% versus 22.2%; HR, 0.63; P=0.009) and those not on insulin (11.5% versus 15.3%; HR, 0.74; P=0.009). Myocardial infarction was reduced with prasugrel by 18% among subjects without DM (7.2% versus 8.7%; HR, 0.82; P=0.006) and by 40% among subjects with DM (8.2% versus 13.2%; HR, 0.60; P<0.001, P(interaction)=0.02). Although TIMI major hemorrhage was increased among subjects without DM on prasugrel (1.6% versus 2.4%; HR, 1.43; P=0.02), the rates were similar among subjects with DM for clopidogrel and prasugrel (2.6% versus 2.5%; HR, 1.06; P=0.81, P(interaction)=0.29). Net clinical benefit with prasugrel was greater for subjects with DM (14.6% versus 19.2%; HR, 0.74; P=0.001) than for subjects without DM (11.5% versus 12.3%; HR, 0.92; P=0.16, P(interaction)=0.05). CONCLUSIONS Subjects with DM tended to have a greater reduction in ischemic events without an observed increase in TIMI major bleeding and therefore a greater net treatment benefit with prasugrel compared with clopidogrel. These data demonstrate that the more intensive oral antiplatelet therapy provided with prasugrel is of particular benefit to patients with DM.",
"title": "Greater clinical benefit of more intensive oral antiplatelet therapy with prasugrel in patients with diabetes mellitus in the trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with prasugrel-Thrombolysis in Myocardial Infarction 38."
},
{
"docid": "8227227",
"text": "The locations of cerebral infarctions were studied in 14 patients with tuberculous meningitis (TBM) and 173 patients with noninflammatory ischemic stroke (IS). In patients with TBM, 75% of infarctions occurred in the “TB zone” supplied by medial striate and thalamoperforating arteries; only 11% occurred in the “IS zone” supplied by lateral striate, anterior choroidal and thalamogeniculate arteries. In patients with IS 29% of infarctions occurred in the IS zone, 29% in the subcortical white matter, and 24% in (or involving) the cerebral cortex. Only 11% occurred in the TB zone. Bilaterally symmetrical infarctions of the TB zone were common with TMB (71%) but rare with IS (5%).",
"title": "Locations of cerebral infarctions in tuberculous meningitis"
},
{
"docid": "5884524",
"text": "BACKGROUND Although unstable coronary artery disease is the most common reason for admission to a coronary care unit, the long-term prognosis of patients with this diagnosis is unknown. This is particularly true for patients with diabetes mellitus, who are known to have a high morbidity and mortality after an acute myocardial infarction. METHODS AND RESULTS Prospectively collected data from 6 different countries in the Organization to Assess Strategies for Ischemic Syndromes (OASIS) registry were analyzed to determine the 2-year prognosis of diabetic and nondiabetic patients who were hospitalized with unstable angina or non-Q-wave myocardial infarction. Overall, 1718 of 8013 registry patients (21%) had diabetes. Diabetic patients had a higher rate of coronary bypass surgery than nondiabetic patients (23% versus 20%, P:<0.001) but had similar rates of catheterization and angioplasty. Diabetes independently predicted mortality (relative risk [RR], 1.57; 95% CI, 1.38 to 1.81; P:<0.001), as well as cardiovascular death, new myocardial infarction, stroke, and new congestive heart failure. Moreover, compared with their nondiabetic counterparts, women had a significantly higher risk than men (RR, 1.98; 95% CI, 1.60 to 2.44; and RR, 1.28; 95% CI, 1.06 to 1.56, respectively). Interestingly, diabetic patients without prior cardiovascular disease had the same event rates for all outcomes as nondiabetic patients with previous vascular disease. CONCLUSIONS Hospitalization for unstable angina or non-Q-wave myocardial infarction predicts a high 2-year morbidity and mortality; this is especially evident for patients with diabetes. Diabetic patients with no previous cardiovascular disease have the same long-term morbidity and mortality as nondiabetic patients with established cardiovascular disease after hospitalization for unstable coronary artery disease.",
"title": "Impact of diabetes on long-term prognosis in patients with unstable angina and non-Q-wave myocardial infarction: results of the OASIS (Organization to Assess Strategies for Ischemic Syndromes) Registry."
},
{
"docid": "12561083",
"text": "BACKGROUND Several studies have demonstrated that women with nonobstructive coronary disease have a high rate of subsequent investigations, rehospitalizations for recurrent chest pain, and repeat coronary angiography. The sex specificity of this finding is unclear. We therefore undertook an evaluation of sex differences in rehospitalization for acute coronary syndrome (ACS) or chest pain in patients with \"angiographically normal\" coronaries. METHODS A retrospective cohort study using prospectively collected angiographic and clinical data on all patients in British Columbia, Canada, presenting for their first cardiac catheterization with suspected ischemic heart disease but angiographically normal coronaries. RESULTS Among 32,856 patients, 7.1% of men versus 23.3% of women were angiographically normal (P < .001). Among angiographically normal patients, women were older and more likely to present with hypertension, prior stroke, chronic obstructive pulmonary disease, and peripheral vascular disease than men, but Canadian Cardiovascular Society class of angina did not vary by sex. Within 1 year, 1.0% died, (19 women, 18 men, P = .27) and 0.6% had a stroke (13 women, 9 men, P = .91). Readmission to hospital for ACS or chest pain requiring catheterization was significantly higher in women compared to men (adjusted OR 4.06; 95% CI 1.15-14.31). CONCLUSIONS In a contemporary, population-based cohort presenting for cardiac catheterization for suspected ischemia, women with angiographically normal coronaries were >4 times more likely to be readmitted to hospital for ACS/chest pain within 180 days compared to men. The observed sex difference has important social and economic implications and suggests that traditional diagnostic methods may not be optimal for women.",
"title": "Angina with \"normal\" coronary arteries: sex differences in outcomes."
},
{
"docid": "33884866",
"text": "OBJECTIVE The sphingosine-1-phosphate (S1P) receptor agonist fingolimod (FTY720), that has shown efficacy in advanced multiple sclerosis clinical trials, decreases reperfusion injury in heart, liver, and kidney. We therefore tested the therapeutic effects of fingolimod in several rodent models of focal cerebral ischemia. To assess the translational significance of these findings, we asked whether fingolimod improved long-term behavioral outcomes, whether delayed treatment was still effective, and whether neuroprotection can be obtained in a second species. METHODS We used rodent models of middle cerebral artery occlusion and cell-culture models of neurotoxicity and inflammation to examine the therapeutic potential and mechanisms of neuroprotection by fingolimod. RESULTS In a transient mouse model, fingolimod reduced infarct size, neurological deficit, edema, and the number of dying cells in the core and periinfarct area. Neuroprotection was accompanied by decreased inflammation, as fingolimod-treated mice had fewer activated neutrophils, microglia/macrophages, and intercellular adhesion molecule-1 (ICAM-1)-positive blood vessels. Fingolimod-treated mice showed a smaller infarct and performed better in behavioral tests up to 15 days after ischemia. Reduced infarct was observed in a permanent model even when mice were treated 4 hours after ischemic onset. Fingolimod also decreased infarct size in a rat model of focal ischemia. Fingolimod did not protect primary neurons against glutamate excitotoxicity or hydrogen peroxide, but decreased ICAM-1 expression in brain endothelial cells stimulated by tumor necrosis factor alpha. INTERPRETATION These findings suggest that anti-inflammatory mechanisms, and possibly vasculoprotection, rather than direct effects on neurons, underlie the beneficial effects of fingolimod after stroke. S1P receptors are a highly promising target in stroke treatment.",
"title": "Fingolimod provides long-term protection in rodent models of cerebral ischemia."
},
{
"docid": "22420524",
"text": "CONTEXT Gallstone disease is a leading cause of morbidity in western countries and carries a high economic burden. Statins decrease hepatic cholesterol biosynthesis and may therefore lower the risk of cholesterol gallstones by reducing the cholesterol concentration in the bile. Data on this association in humans are scarce. OBJECTIVE To study the association between the use of statins, fibrates, or other lipid-lowering agents and the risk of incident gallstone disease followed by cholecystectomy. DESIGN, SETTING, AND PARTICIPANTS Case-control analysis using the UK-based General Practice Research Database. Incident patients between 1994 and 2008 and 4 controls per each patient were identified and matched on age, sex, general practice, calendar time, and years of history in the database. The study population was 76% women and the mean (SD) age was 53.4 (15.0) years at the index date. Conditional logistic regression was used to estimate the odds ratio (OR) of developing gallstones followed by cholecystectomy in relation to exposure to lipid-lowering agents, stratified by exposure timing and duration. The ORs and 95% confidence intervals (CIs) were adjusted for smoking, body mass index, ischemic heart disease, stroke, and estrogen use. MAIN OUTCOME MEASURE The adjusted OR (AOR) for developing gallstone disease followed by cholecystectomy in relation to exposure to lipid-lowering agents. RESULTS A total of 27,035 patients with cholecystectomy and 106,531 matched controls were identified, including 2396 patients and 8868 controls who had statin use. Compared with nonuse, current statin use (last prescription recorded within 90 days before the first-time diagnosis of the disease) was 1.0% for patients and 0.8% for controls (AOR, 1.10; 95% CI, 0.95-1.27) for 1 to 4 prescriptions; 2.6% vs 2.4% (AOR, 0.85; 95% CI, 0.77-0.93) for 5 to 19 prescriptions, and 3.2% vs 3.7% (AOR, 0.64; 95% CI, 0.59-0.70) for 20 or more prescriptions. The AORs for current use of statins defined as 20 or more prescriptions were similar (around 0.6) across age, sex, and body mass index categories, and across the statin class. CONCLUSION Long-term use of statins was associated with a decreased risk of gallstones followed by cholecystectomy.",
"title": "Statin use and risk of gallstone disease followed by cholecystectomy."
},
{
"docid": "27466734",
"text": "Objectives To develop and validate updated QRISK3 prediction algorithms to estimate the 10 year risk of cardiovascular disease in women and men accounting for potential new risk factors. Design Prospective open cohort study. Setting General practices in England providing data for the QResearch database. Participants 1309 QResearch general practices in England: 981 practices were used to develop the scores and a separate set of 328 practices were used to validate the scores. 7.89 million patients aged 25-84 years were in the derivation cohort and 2.67 million patients in the validation cohort. Patients were free of cardiovascular disease and not prescribed statins at baseline. Methods Cox proportional hazards models in the derivation cohort to derive separate risk equations in men and women for evaluation at 10 years. Risk factors considered included those already in QRISK2 (age, ethnicity, deprivation, systolic blood pressure, body mass index, total cholesterol: high density lipoprotein cholesterol ratio, smoking, family history of coronary heart disease in a first degree relative aged less than 60 years, type 1 diabetes, type 2 diabetes, treated hypertension, rheumatoid arthritis, atrial fibrillation, chronic kidney disease (stage 4 or 5)) and new risk factors (chronic kidney disease (stage 3, 4, or 5), a measure of systolic blood pressure variability (standard deviation of repeated measures), migraine, corticosteroids, systemic lupus erythematosus (SLE), atypical antipsychotics, severe mental illness, and HIV/AIDs). We also considered erectile dysfunction diagnosis or treatment in men. Measures of calibration and discrimination were determined in the validation cohort for men and women separately and for individual subgroups by age group, ethnicity, and baseline disease status. Main outcome measures Incident cardiovascular disease recorded on any of the following three linked data sources: general practice, mortality, or hospital admission records. Results 363 565 incident cases of cardiovascular disease were identified in the derivation cohort during follow-up arising from 50.8 million person years of observation. All new risk factors considered met the model inclusion criteria except for HIV/AIDS, which was not statistically significant. The models had good calibration and high levels of explained variation and discrimination. In women, the algorithm explained 59.6% of the variation in time to diagnosis of cardiovascular disease (R2, with higher values indicating more variation), and the D statistic was 2.48 and Harrell's C statistic was 0.88 (both measures of discrimination, with higher values indicating better discrimination). The corresponding values for men were 54.8%, 2.26, and 0.86. Overall performance of the updated QRISK3 algorithms was similar to the QRISK2 algorithms. Conclusion Updated QRISK3 risk prediction models were developed and validated. The inclusion of additional clinical variables in QRISK3 (chronic kidney disease, a measure of systolic blood pressure variability (standard deviation of repeated measures), migraine, corticosteroids, SLE, atypical antipsychotics, severe mental illness, and erectile dysfunction) can help enable doctors to identify those at most risk of heart disease and stroke.",
"title": "Development and validation of QRISK3 risk prediction algorithms to estimate future risk of cardiovascular disease: prospective cohort study"
},
{
"docid": "6325527",
"text": "Although blood–brain barrier (BBB) compromise is central to the etiology of diverse central nervous system (CNS) disorders, endothelial receptor proteins that control BBB function are poorly defined. The endothelial G-protein-coupled receptor (GPCR) Gpr124 has been reported to be required for normal forebrain angiogenesis and BBB function in mouse embryos, but the role of this receptor in adult animals is unknown. Here Gpr124 conditional knockout (CKO) in the endothelia of adult mice did not affect homeostatic BBB integrity, but resulted in BBB disruption and microvascular hemorrhage in mouse models of both ischemic stroke and glioblastoma, accompanied by reduced cerebrovascular canonical Wnt–β-catenin signaling. Constitutive activation of Wnt–β-catenin signaling fully corrected the BBB disruption and hemorrhage defects of Gpr124-CKO mice, with rescue of the endothelial gene tight junction, pericyte coverage and extracellular-matrix deficits. We thus identify Gpr124 as an endothelial GPCR specifically required for endothelial Wnt signaling and BBB integrity under pathological conditions in adult mice. This finding implicates Gpr124 as a potential therapeutic target for human CNS disorders characterized by BBB disruption.",
"title": "Gpr124 is essential for blood–brain barrier integrity in central nervous system disease"
},
{
"docid": "16180601",
"text": "OBJECTIVE Serum soluble corin has been associated with stroke. However, whether it is associated with stroke prognosis has not yet been studied. Therefore, we aimed to study the association of serum soluble corin with risk of poor outcomes within 3 months after stroke. METHODS We followed 522 stroke patients for 3 months to identify major disability, death and vascular events. Serum soluble corin was measured at baseline for all participants. Logistic regression was used to examine the associations of baseline serum soluble corin with outcomes of stroke, adjusting for age, sex, baseline NIHSS score, hours from onset to hospitalization, smoking, drinking, hypertension, diabetes, coronary heart disease, atrial fibrillation, family history of stroke, and stroke subtype. RESULTS Patients with high corin had a significantly lower crude risk for the composite outcome of major disability or death (OR = 0.64, 95%CI: 0.43-0.96) than patients with low corin (the lowest tertile). After adjustment for age and baseline NIHSS score, patients with high corin still had a significantly lower risk for the composite outcome of major disability or death (OR = 0.60, 95%CI: 0.36-0.99). This association became bottom line significant after additionally adjusting for other conventional factors (OR = 0.61, P = 0.058). No association was found between serum soluble corin and other composite outcomes. CONCLUSION Serum soluble corin deficiency predicted risk for major disability within 3 months after stroke, independent of baseline neurological deficient. Our results may indicate a probable role of corin in stroke prognosis.",
"title": "Serum Soluble Corin Deficiency Predicts Major Disability within 3 Months after Acute Stroke"
},
{
"docid": "8595678",
"text": "BACKGROUND The MTHFR 677C→T polymorphism has been associated with raised homocysteine concentration and increased risk of stroke. A previous overview showed that the effects were greatest in regions with low dietary folate consumption, but differentiation between the effect of folate and small-study bias was difficult. A meta-analysis of randomised trials of homocysteine-lowering interventions showed no reduction in coronary heart disease events or stroke, but the trials were generally set in populations with high folate consumption. We aimed to reduce the effect of small-study bias and investigate whether folate status modifies the association between MTHFR 677C→T and stroke in a genetic analysis and meta-analysis of randomised controlled trials. METHODS We established a collaboration of genetic studies consisting of 237 datasets including 59,995 individuals with data for homocysteine and 20,885 stroke events. We compared the genetic findings with a meta-analysis of 13 randomised trials of homocysteine-lowering treatments and stroke risk (45,549 individuals, 2314 stroke events, 269 transient ischaemic attacks). FINDINGS The effect of the MTHFR 677C→T variant on homocysteine concentration was larger in low folate regions (Asia; difference between individuals with TT versus CC genotype, 3·12 μmol/L, 95% CI 2·23 to 4·01) than in areas with folate fortification (America, Australia, and New Zealand, high; 0·13 μmol/L, -0·85 to 1·11). The odds ratio (OR) for stroke was also higher in Asia (1·68, 95% CI 1·44 to 1·97) than in America, Australia, and New Zealand, high (1·03, 0·84 to 1·25). Most randomised trials took place in regions with high or increasing population folate concentrations. The summary relative risk (RR) of stroke in trials of homocysteine-lowering interventions (0·94, 95% CI 0·85 to 1·04) was similar to that predicted for the same extent of homocysteine reduction in large genetic studies in populations with similar folate status (predicted RR 1·00, 95% CI 0·90 to 1·11). Although the predicted effect of homocysteine reduction from large genetic studies in low folate regions (Asia) was larger (RR 0·78, 95% CI 0·68 to 0·90), no trial has evaluated the effect of lowering of homocysteine on stroke risk exclusively in a low folate region. INTERPRETATION In regions with increasing levels or established policies of population folate supplementation, evidence from genetic studies and randomised trials is concordant in suggesting an absence of benefit from lowering of homocysteine for prevention of stroke. Further large-scale genetic studies of the association between MTHFR 677C→T and stroke in low folate settings are needed to distinguish effect modification by folate from small-study bias. If future randomised trials of homocysteine-lowering interventions for stroke prevention are undertaken, they should take place in regions with low folate consumption. FUNDING Full funding sources listed at end of paper (see Acknowledgments).",
"title": "Effect modification by population dietary folate on the association between MTHFR genotype, homocysteine, and stroke risk: a meta-analysis of genetic studies and randomised trials"
},
{
"docid": "25416944",
"text": "PURPOSE Mutations in the leucine rich, glioma inactivated gene (LGI1) were recently described in a small number of families with autosomal dominant lateral temporal epilepsy (ADLTE). ADLTE is characterized by partial seizures with symptoms suggestive of a lateral temporal onset, including frequent auditory aura. Here we report the results of clinical and genetic analyses of two newly identified families with ADTLE. METHODS We identified two families whose seizure semiology was suggestive of ADLTE. Evaluation included a detailed history and neurologic examination, as well as collection of DNA. The coding sequence of the LGI1 gene from affected subjects from both families was analyzed for evidence of mutation. RESULTS Each patient had a history of partial seizures, often with secondary generalization earlier in the course. Auditory aura was reported by approximately two thirds of affected patients in each pedigree. Novel mutations in LGI1 were detected in both families. A heterozygous single-nucleotide deletion at position 329 (del 329C) was detected in affected individuals from one family, whereas patients from the second family had a nonsynonymous variation, corresponding to C435G. CONCLUSIONS We identified two novel mutations in the LGI1 gene. The phenotype of these two families was similar to that of other kindreds with ADLTE, as auditory aura was absent in one third of affected individuals. Our results further support that LGI1 mutations should be considered in patients with a history of partial seizures if the semiology of seizures is consistent with the onset in the lateral temporal lobe.",
"title": "Autosomal dominant lateral temporal epilepsy: two families with novel mutations in the LGI1 gene."
}
] |
PLAIN-95
|
How Grapefruit Affects Prescription Drugs
|
[
{
"docid": "MED-3000",
"text": "An increased risk for colorectal cancer has been consistently reported for long-time consumption of cooked and processed red meat. This has frequently been attributed to chemical carcinogens arising during the cooking process of meat. Long-time fish or poultry consumption apparently does not increase the risk, although similar or higher concentrations of chemical carcinogens were recorded in their preparation for consumption. The geographic epidemiology of colorectal cancer seems to correspond to regions with a high rate of beef consumption. Countries with a virtual absence of beef in the diet (India) or where preferably lamb or goat meat is consumed (several Arabic countries) reveal low rates of colorectal cancer. In China, pork consumption has a long tradition, with an intermediate colorectal cancer rate. In Japan and Korea, large scale beef and pork imports started after World War II or after the Korean War. A steep rise in colorectal cancer incidence was noted after 1970 in Japan and 1990 in Korea. The consumption of undercooked beef (e.g., shabu-shabu, Korean yukhoe and Japanese yukke) became very popular in both countries. The available data are compatible with the interpretation that a specific beef factor, suspected to be one or more thermoresistant potentially oncogenic bovine viruses (e.g., polyoma-, papilloma- or possibly single-stranded DNA viruses) may contaminate beef preparations and lead to latent infections in the colorectal tract. Preceding, concomitant or subsequent exposure to chemical carcinogens arising during cooking procedures should result in increased risk for colorectal cancer synergistic with these infections. Copyright © 2011 UICC.",
"title": "Red meat consumption and cancer: reasons to suspect involvement of bovine infectious factors in colorectal cancer."
},
{
"docid": "MED-5327",
"text": "OBJECTIVE: To investigate the associations between dietary patterns and mental health in early adolescence. METHOD: The Western Australian Pregnancy Cohort (Raine) Study is a prospective study of 2900 pregnancies recruited from 1989-1992. At 14 years of age (2003-2006; n=1324), the Child Behaviour Checklist (CBCL) was used to assess behaviour (characterising mental health status), with higher scores representing poorer behaviour. Two dietary patterns (Western and Healthy) were identified using factor analysis and food group intakes estimated by a 212-item food frequency questionnaire. Relationships between dietary patterns, food group intakes and behaviour were examined using general linear modelling following adjustment for potential confounding factors at age 14: total energy intake, body mass index, physical activity, screen use, family structure, income and functioning, gender and maternal education at pregnancy. RESULTS: Higher total (b=2.20, 95% CI=1.06, 3.35), internalizing (withdrawn/depressed) (b=1.25, 95% CI=0.15, 2.35) and externalizing (delinquent/aggressive) (b=2.60, 95% CI=1.51, 3.68) CBCL scores were significantly associated with the Western dietary pattern, with increased intakes of takeaway foods, confectionary and red meat. Improved behavioural scores were significantly associated with higher intakes of leafy green vegetables and fresh fruit (components of the Healthy pattern). CONCLUSION: These findings implicate a Western dietary pattern in poorer behavioural outcomes for adolescents. Better behavioural outcomes were associated with a higher intake of fresh fruit and leafy green vegetables.",
"title": "The association between dietary patterns and mental health in early adolescence."
},
{
"docid": "MED-3204",
"text": "Grapefruit is a healthy addition to a well-balanced diet. However, the fruit has been shown to affect the metabolism of many medications, increasing the risk of toxicity and adverse effects. Characteristics of oral medications that may interact with grapefruit include extensive metabolism through the intestinal cytochrome P450 3A4 system, low bioavailability, and a narrow therapeutic index. Prominent medications known to interact with grapefruit include statins, antiarrhythmic agents, immunosuppressive agents, and calcium channel blockers. There are equally effective alternatives to these drug classes that do not have the potential to interact with grapefruit. These alternative drugs may be substituted if a patient experiences or is at risk of a grapefruit-drug interaction. Patients also may choose to exclude grapefruit from their diets and consume other fruits, including other types of citrus, to avoid an interaction.",
"title": "Management of grapefruit-drug interactions."
},
{
"docid": "MED-5329",
"text": "OBJECTIVE: This study was conducted to demonstrate the effectiveness of a strictly vegetarian, very low-fat diet on cardiac risk factor modification. METHODS: Five hundred men and women, participants in an intensive 12-day live-in program, were studied. The program focused on dietary modification, moderate exercise, and stress management at a hospital-based health-center. RESULTS: During this short time period, cardiac risk factors improved: there was an average reduction of total serum cholesterol of 11% (p < 0.001), of blood pressure of 6% (p < 0.001) and a weight loss of 2.5 kg for men and 1 kg for women. Serum triglycerides did not increase except for two subgroups: females age > or = 65 years with serum cholesterol < 6.5 mmol/L and for females 50 to 64 years with baseline serum cholesterol between 5.2-6.5 mmol/L. High-density lipoprotein cholesterol measured on 66 subjects decreased by 19%. CONCLUSION: A strict, very low-fat vegetarian diet free from all animal products combined with lifestyle changes that include exercise and weight loss is an effective way to lower serum cholesterol and blood pressure.",
"title": "Rapid reduction of serum cholesterol and blood pressure by a twelve-day, very low fat, strictly vegetarian diet."
},
{
"docid": "MED-3210",
"text": "Folklore has suggested that consuming grapefruit may promote weight control. Sparse data exist to support this hypothesis, although there is some evidence of health promotion effects with regard to blood pressure control and modulation of circulating lipids. The aim of this randomized controlled trial was to prospectively evaluate the role of grapefruit in reducing body weight and blood pressure and in promoting improvements in the lipid profile in overweight adults (N = 74). Following a 3-week washout diet low in bioactive-rich fruits and vegetables, participants were randomized to either the control diet (n = 32) or daily grapefruit (n = 42) in the amount of one half of a fresh Rio-Red grapefruit with each meal (3× daily) for 6 weeks. No differences between group in weight, blood pressure, or lipids were demonstrated. Grapefruit consumption was associated with modest weight loss (-0.61 ± 2.23 kg, P = .097), a significant reduction in waist circumference (-2.45 ± 0.60 cm, P = .0002), and a significant reduction in systolic blood pressure (-3.21 ± 10.13 mm Hg, P = .03) compared with baseline values. Improvements were observed in circulating lipids of those consuming grapefruit, with total cholesterol and low-density lipoprotein significantly decreasing by -11.7 mg/dL (P = .002) and -18.7 mg/dL (P < .001), respectively, compared with baseline values. This study suggests that consumption of grapefruit daily for 6 weeks does not significantly decrease body weight, lipids, or blood pressure as compared with the control condition. However, the improvements in blood pressure and lipids demonstrated in the intervention group suggest that grapefruit should be further evaluated in the context of obesity and cardiovascular disease prevention. Copyright © 2012 Elsevier Inc. All rights reserved.",
"title": "The effects of daily consumption of grapefruit on body weight, lipids, and blood pressure in healthy, overweight adults."
},
{
"docid": "MED-5341",
"text": "The present study investigated the effects of a diet and exercise intervention on known breast cancer (BCa) risk factors, including estrogen, obesity, insulin, and insulin-like growth factor-I (IGF-I), in overweight/obese, postmenopausal women. In addition, using the subjects' pre- and postintervention serum in vitro, serum-stimulated growth and apoptosis of three estrogen receptor-positive BCa cell lines were studied. The women where placed on a low-fat (10-15% kcal), high-fiber (30-40 g per 1,000 kcal/day) diet and attended daily exercise classes for 2 wk. Serum estradiol was reduced in the women on hormone treatment (HT; n = 28) as well as those not on HT (n = 10). Serum insulin and IGF-I were significantly reduced in all women, whereas IGF binding protein-1 was increased significantly. In vitro growth of the BCa cell lines was reduced by 6.6% for the MCF-7 cells, 9.9% for the ZR-75-1 cells, and 18.5% for the T-47D cells. Apoptosis was increased by 20% in the ZR-75-1 cells, 23% in the MCF-7 cells, and 30% in the T-47D cells (n = 12). These results show that a very-low-fat, high-fiber diet combined with daily exercise results in major reductions in risk factors for BCa while subjects remained overweight/obese. These in vivo serum changes slowed the growth and induced apoptosis in serum-stimulated BCa cell lines in vitro.",
"title": "Effects of a low-fat, high-fiber diet and exercise program on breast cancer risk factors in vivo and tumor cell growth and apoptosis in vitro."
},
{
"docid": "MED-3208",
"text": "This study evaluated the effect of adding fruit or oats to the diet of free-living women on energy consumption and body weight. Fruit and oat cookies had the same amount of fiber and total calories ( approximately 200 kcal), but differed in energy density. We analyzed data from a clinical trial conducted in a primary care unit in Rio de Janeiro, Brazil. Forty-nine women, ages ranging from 30 to 50 years, with body mass index (BMI)>25 kg/m2, were randomly chosen to add three apples (0.63 kcal/g energy density) or three pears (0.64 kcal/g energy density) or three oat cookies (3.7 kcal/g energy density) to their usual diet for 10 weeks. Fiber composition was similar ( approximately 6g). Statistical analysis of the repeated measures of dietary composition and body weight were analyzed using mixed model procedures. Results showed a significant decrease in the energy density during the follow-up (-1.23 kcal/g, p<0.04, and -1.29 kcal/g, p<0.05) for apples and pears, respectively, compared to the oat group. The energy intake also decreased significantly (-25.05 and -19.66 kcal/day) for the apple and pear group, respectively, but showed a small increase (+0.93) for the oat group. Apples and pears were also associated (p<0.001) with weight reduction (-0.93 kg for the apple and -0.84 for the pear group), whereas weight was unchanged (+0.21; p=0.35) in the oat group. Results suggest that energy densities of fruits, independent of their fiber amount can reduce energy consumption and body weight over time.",
"title": "A low-energy-dense diet adding fruit reduces weight and energy intake in women."
},
{
"docid": "MED-5339",
"text": "Recently, it has been suggested that the Escherichia coli causing urinary tract infection (UTI) may come from meat and animals. The purpose was to investigate if a clonal link existed between E. coli from animals, meat and UTI patients. Twenty-two geographically and temporally matched B2 E. coli from UTI patients, community-dwelling humans, broiler chicken meat, pork, and broiler chicken, previously identified to exhibit eight virulence genotypes by microarray-detection of approximately 300 genes, were investigated for clonal relatedness by PFGE. Nine isolates were selected and tested for in vivo virulence in the mouse model of ascending UTI. UTI and community-dwelling human strains were closely clonally related to meat strains. Several human derived strains were also clonally interrelated. All nine isolates regardless of origin were virulent in the UTI model with positive urine, bladder and kidney cultures. Further, isolates with the same gene profile also yielded similar bacterial counts in urine, bladder and kidneys. This study showed a clonal link between E. coli from meat and humans, providing solid evidence that UTI is zoonosis. The close relationship between community-dwelling human and UTI isolates may indicate a point source spread, e.g. through contaminated meat.",
"title": "Is Escherichia coli urinary tract infection a zoonosis? Proof of direct link with production animals and meat."
},
{
"docid": "MED-4160",
"text": "CONTEXT: Despite decades of accumulated observational evidence, the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain. OBJECTIVE: To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States. DESIGN: Estrogen plus progestin component of the Women's Health Initiative, a randomized controlled primary prevention trial (planned duration, 8.5 years) in which 16608 postmenopausal women aged 50-79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993-1998. INTERVENTIONS: Participants received conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, in 1 tablet (n = 8506) or placebo (n = 8102). MAIN OUTCOMES MEASURES: The primary outcome was coronary heart disease (CHD) (nonfatal myocardial infarction and CHD death), with invasive breast cancer as the primary adverse outcome. A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke, pulmonary embolism (PE), endometrial cancer, colorectal cancer, hip fracture, and death due to other causes. RESULTS: On May 31, 2002, after a mean of 5.2 years of follow-up, the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits. This report includes data on the major clinical outcomes through April 30, 2002. Estimated hazard ratios (HRs) (nominal 95% confidence intervals [CIs]) were as follows: CHD, 1.29 (1.02-1.63) with 286 cases; breast cancer, 1.26 (1.00-1.59) with 290 cases; stroke, 1.41 (1.07-1.85) with 212 cases; PE, 2.13 (1.39-3.25) with 101 cases; colorectal cancer, 0.63 (0.43-0.92) with 112 cases; endometrial cancer, 0.83 (0.47-1.47) with 47 cases; hip fracture, 0.66 (0.45-0.98) with 106 cases; and death due to other causes, 0.92 (0.74-1.14) with 331 cases. Corresponding HRs (nominal 95% CIs) for composite outcomes were 1.22 (1.09-1.36) for total cardiovascular disease (arterial and venous disease), 1.03 (0.90-1.17) for total cancer, 0.76 (0.69-0.85) for combined fractures, 0.98 (0.82-1.18) for total mortality, and 1.15 (1.03-1.28) for the global index. Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events, 8 more strokes, 8 more PEs, and 8 more invasive breast cancers, while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures. The absolute excess risk of events included in the global index was 19 per 10 000 person-years. CONCLUSIONS: Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women. All-cause mortality was not affected during the trial. The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases, and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD.",
"title": "Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized cont..."
},
{
"docid": "MED-3201",
"text": "Background Reducing dietary energy density has proven to be an effective strategy to reduce energy intakes and promote weight control. This effect appears most robust when a low energy dense preload is consumed before meals. Yet, much discussion continues regarding the optimal form of a preload. The purpose of the present study was to compare effects of a solid (grapefruit), liquid (grapefruit juice) and water preload consumed prior to breakfast, lunch and dinner in the context of caloric restriction. Methods Eighty-five obese adults (BMI 30-39.9) were randomly assigned to (127 g) grapefruit (GF), grapefruit juice (GFJ) or water preload for 12 weeks after completing a 2-week caloric restriction phase. Preloads were matched for weight, calories, water content, and energy density. Weekly measures included blood pressure, weight, anthropometry and 24-hour dietary intakes. Resting energy expenditure, body composition, physical performance and cardiometabolic risk biomarkers were assessed. Results The total amount (grams) of food consumed did not change over time. Yet, after preloads were combined with caloric restriction, average dietary energy density and total energy intakes decreased by 20-29% from baseline values. Subjects experienced 7.1% weight loss overall, with significant decreases in percentage body, trunk, android and gynoid fat, as well as waist circumferences (-4.5 cm). However, differences were not statistically significant among groups. Nevertheless, the amount and direction of change in serum HDL-cholesterol levels in GF (+6.2%) and GFJ (+8.2%) preload groups was significantly greater than water preload group (-3.7%). Conclusions These data indicate that incorporating consumption of a low energy dense dietary preload in a caloric restricted diet is a highly effective weight loss strategy. But, the form of the preload did not have differential effects on energy balance, weight loss or body composition. It is notable that subjects in GF and GFJ preload groups experienced significantly greater benefits in lipid profiles. Trial registration ClinicalTrials.gov NCT00581074",
"title": "Effects of grapefruit, grapefruit juice and water preloads on energy balance, weight loss, body composition, and cardiometabolic risk in free-living obese adults"
},
{
"docid": "MED-3200",
"text": "In vitro and in vivo studies have shown that cytochrome P450 3A4 (CYP3A4) is involved in the metabolism of oestrogens. There is evidence that grapefruit, an inhibitor of CYP3A4, increases plasma oestrogen concentrations. Since it is well established that oestrogen is associated with breast cancer risk, it is plausible that regular intake of grapefruit would increase a woman's risk of breast cancer. We investigated the association of grapefruit intake with breast cancer risk in the Hawaii–Los Angeles Multiethnic Cohort Study, a prospective cohort that includes over 50 000 postmenopausal women from five racial/ethnic groups. A total of 1657 incident breast cancer cases were available for analysis. Grapefruit intake was significantly associated with an increased risk of breast cancer (relative risk=1.30, 95% confidence interval 1.06–1.58) for subjects in the highest category of intake, that is, one-quarter grapefruit or more per day, compared to non-consumers (Ptrend=0.015). An increased risk of similar magnitude was seen in users of oestrogen therapy, users of oestrogen+progestin therapy, and among never users of hormone therapy. Grapefruit intake may increase the risk of breast cancer among postmenopausal women.",
"title": "Prospective study of grapefruit intake and risk of breast cancer in postmenopausal women: the Multiethnic Cohort Study"
},
{
"docid": "MED-4158",
"text": "Background Postmenopausal conjugated equine estrogens (CEE) therapies increase the risk of cognitive impairment in women aged 65 years or older and are associated with smaller regional brain volumes; however, the link between these two phenomena has not been established. Methods Standardized magnetic resonance imaging was performed on 1,403 women, 1–4 years after they had participated in randomized placebo-controlled clinical trials of CEE-based therapies. Women included in this report were aged 65–80 years and free of dementia and mild cognitive impairment (MCI) when originally enrolled in the trials, which lasted an average of 4–6 years and were conducted at 14 academic U.S. medical centers. The associations that regional brain volumes and ischemic lesion volumes had with the development of cognitive impairment (i.e., dementia or MCI) were contrasted between treatment groups using analyses of covariance. Results Fifty-three women developed MCI or probable dementia during follow-up. Among women who had been prescribed CEE-based therapies, cognitive impairment was associated with relatively smaller hippocampal (p = .0002) and total brain volumes (p = .03). Qualitatively, these associations appeared to be independent of their level of pretreatment cognitive function. Among women who had been prescribed placebo, these relationships were not evident; instead, cognitive impairment was associated with greater ischemic lesion volume in the frontal lobe (p = .007) and overall (p = .02). Conclusion A mechanism by which CEE-based postmenopausal hormone therapy induces cognitive impairment appears to be through increased brain atrophy.",
"title": "Brain Volumes, Cognitive Impairment, and Conjugated Equine Estrogens"
},
{
"docid": "MED-3202",
"text": "1. The effects of grapefruit juice and naringenin on the activity of the human cytochrome P450 isoform CYP1A2 were evaluated using caffeine as a probe substrate. 2. In vitro naringin was a potent competitive inhibitor of caffeine 3-demethylation by human liver microsomes (Ki = 7-29 microM). 3. In vivo grapefruit juice (1.2 l day-1 containing 0.5 g l-1 naringin, the glycone form of naringenin) decreased the oral clearance of caffeine by 23% (95% CI: 7%-30%) and prolonged its half-life by 31% (95% CI: 20%-44%) (n = 12). 4. We conclude that grapefruit juice and naringenin inhibit CYP1A2 activity in man. However, the small effect on caffeine clearance in vivo suggests that in general the ingestion of grapefruit juice should not cause clinically significant inhibition of the metabolism of other drugs that are substrates of CYPIA2.",
"title": "Inhibitory effect of grapefruit juice and its bitter principal, naringenin, on CYP1A2 dependent metabolism of caffeine in man."
},
{
"docid": "MED-3207",
"text": "Summary Grapefruit is a popular, tasty and nutritive fruit enjoyed globally. Biomedical evidence in the last 10 years has, however, shown that consumption of grapefruit or its juice is associated with drug interactions, which, in some cases, have been fatal. Grapefruit-induced drug interactions are unique in that the cytochrome P450 enzyme CYP3A4, which metabolises over 60% of commonly prescribed drugs as well as other drug transporter proteins such as P-glycoprotein and organic cation transporter proteins, which are all expressed in the intestines, are involved. However, the extent to which grapefruit–drug interactions impact on clinical settings has not been fully determined, probably because many cases are not reported. It has recently emerged that grapefruit, by virtue of its rich flavonoid content, is beneficial in the management of degenerative diseases such as diabetes and cardiovascular disorders. This potentially explosive subject is reviewed here.",
"title": "The grapefruit: an old wine in a new glass? Metabolic and cardiovascular perspectives"
},
{
"docid": "MED-4126",
"text": "Aspartame is a widely used artificial sweetener that has been linked to pediatric and adolescent migraines. Upon ingestion, aspartame is broken, converted, and oxidized into formaldehyde in various tissues. We present the first case series of aspartame-associated migraines related to clinically relevant positive reactions to formaldehyde on patch testing.",
"title": "Formaldehyde, aspartame, and migraines: a possible connection."
},
{
"docid": "MED-4161",
"text": "We assessed the significance and nature of delusions in frontotemporal lobar degeneration (FTLD), an important cause of young-onset dementia with prominent neuropsychiatric features that remain incompletely characterised. The case notes of all patients meeting diagnostic criteria for FTLD attending a tertiary level cognitive disorders clinic over a three year period were retrospectively reviewed and eight patients with a history of delusions were identified. All patients underwent detailed clinical and neuropsychological evaluation and brain MRI. The diagnosis was confirmed pathologically in two cases. The estimated prevalence of delusions was 14 %. Delusions were an early, prominent and persistent feature. They were phenomenologically diverse; however paranoid and somatic delusions were prominent. Behavioural variant FTLD was the most frequently associated clinical subtype and cerebral atrophy was bilateral or predominantly right-sided in most cases. We conclude that delusions may be a clinical issue in FTLD, and this should be explored further in future work.",
"title": "Delusions in frontotemporal lobar degeneration"
},
{
"docid": "MED-5322",
"text": "BACKGROUND/AIMS: This study aimed to investigate the quantitative and qualitative changes of bacteria, Bacteroides, Bifidobacterium and Clostridium cluster IV in faecal microbiota associated with a vegetarian diet. METHODS: Bacterial abundances were measured in faecal samples of 15 vegetarians and 14 omnivores using quantitative PCR. Diversity was assessed with PCR-DGGE fingerprinting, principal component analysis (PCA) and Shannon diversity index. RESULTS: Vegetarians had a 12% higher abundance of bacterial DNA than omnivores, a tendency for less Clostridium cluster IV (31.86 +/- 17.00%; 36.64 +/- 14.22%) and higher abundance of Bacteroides (23.93 +/- 10.35%; 21.26 +/- 8.05%), which were not significant due to high interindividual variations. PCA suggested a grouping of bacteria and members of Clostridium cluster IV. Two bands appeared significantly more frequently in omnivores than in vegetarians (p < 0.005 and p < 0.022). One was identified as Faecalibacterium sp. and the other was 97.9% similar to the uncultured gut bacteriumDQ793301. CONCLUSIONS: A vegetarian diet affects the intestinal microbiota, especially by decreasing the amount and changing the diversity of Clostridium cluster IV. It remains to be determined how these shifts might affect the host metabolism and disease risks. Copyright 2009 S. Karger AG, Basel.",
"title": "Characterization of bacteria, clostridia and Bacteroides in faeces of vegetarians using qPCR and PCR-DGGE fingerprinting."
},
{
"docid": "MED-5324",
"text": "Obesity has important health consequences, including elevating risk for heart disease, diabetes, and cancer. A high-fat diet is known to contribute to obesity. Little is known regarding the effect of a high-fat diet on pulmonary function, despite the dramatic increase in the prevalence of respiratory ailments (e.g., asthma). The purpose of our study was to determine whether a high-fat meal (HFM) would increase airway inflammation and decrease pulmonary function in healthy subjects. Pulmonary function tests (PFT) (forced expiratory volume in 1-s, forced vital capacity, forced expiratory flow at 25-75% of vital capacity) and exhaled nitric oxide (eNO; airway inflammation) were performed in 20 healthy (10 men, 10 women), inactive subjects (age 21.9 +/- 0.4 years) pre and 2 h post HFM (1 g fat/1 kg body weight; 74.2 +/- 4.1 g fat). Total cholesterol, triglycerides, and C-reactive protein (CRP; systemic inflammation) were determined via a venous blood sample pre and post HFM. Body composition was measured via dual energy X-ray absorptiometry. The HFM significantly increased total cholesterol by 4 +/- 1%, and triglycerides by 93 +/- 3%. ENO also increased (p < 0.05) due to the HFM by 19 +/- 1% (pre 17.2 +/- 1.6; post 20.6 +/- 1.7 ppb). ENO and triglycerides were significantly related at baseline and post-HFM (r = 0.82, 0.72 respectively). Despite the increased eNO, PFT or CRP did not change (p > 0.05) with the HFM. These results demonstrate that a HFM, which leads to significant increases in total cholesterol, and especially triglycerides, increases exhaled NO. This suggests that a high-fat diet may contribute to chronic inflammatory diseases of the airway and lung.",
"title": "Effects of a high-fat meal on pulmonary function in healthy subjects."
},
{
"docid": "MED-5335",
"text": "Three recent case-control studies conclude that diets high in animal fat or cholesterol are associated with a substantial increase in risk for Parkinson's disease (PD); in contrast, fat of plant origin does not appear to increase risk. Whereas reported age-adjusted prevalence rates of PD tend to be relatively uniform throughout Europe and the Americas, sub-Saharan black Africans, rural Chinese, and Japanese, groups whose diets tend to be vegan or quasi-vegan, appear to enjoy substantially lower rates. Since current PD prevalence in African-Americans is little different from that in whites, environmental factors are likely to be responsible for the low PD risk in black Africans. In aggregate, these findings suggest that vegan diets may be notably protective with respect to PD. However, they offer no insight into whether saturated fat, compounds associated with animal fat, animal protein, or the integrated impact of the components of animal products mediates the risk associated with animal fat consumption. Caloric restriction has recently been shown to protect the central dopaminergic neurons of mice from neurotoxins, at least in part by induction of heat-shock proteins; conceivably, the protection afforded by vegan diets reflects a similar mechanism. The possibility that vegan diets could be therapeutically beneficial in PD, by slowing the loss of surviving dopaminergic neurons, thus retarding progression of the syndrome, may merit examination. Vegan diets could also be helpful to PD patients by promoting vascular health and aiding blood-brain barrier transport of L-dopa. Copyright 2001 Harcourt Publishers Ltd.",
"title": "Does a vegan diet reduce risk for Parkinson's disease?"
},
{
"docid": "MED-5342",
"text": "Background The physical health status of vegetarians has been extensively reported, but there is limited research regarding the mental health status of vegetarians, particularly with regard to mood. Vegetarian diets exclude fish, the major dietary source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), critical regulators of brain cell structure and function. Omnivorous diets low in EPA and DHA are linked to impaired mood states in observational and experimental studies. Methods We examined associations between mood state and polyunsaturated fatty acid intake as a result of adherence to a vegetarian or omnivorous diet in a cross-sectional study of 138 healthy Seventh Day Adventist men and women residing in the Southwest. Participants completed a quantitative food frequency questionnaire, Depression Anxiety Stress Scale (DASS), and Profile of Mood States (POMS) questionnaires. Results Vegetarians (VEG:n = 60) reported significantly less negative emotion than omnivores (OMN:n = 78) as measured by both mean total DASS and POMS scores (8.32 ± 0.88 vs 17.51 ± 1.88, p = .000 and 0.10 ± 1.99 vs 15.33 ± 3.10, p = .007, respectively). VEG reported significantly lower mean intakes of EPA (p < .001), DHA (p < .001), as well as the omega-6 fatty acid, arachidonic acid (AA; p < .001), and reported higher mean intakes of shorter-chain α-linolenic acid (p < .001) and linoleic acid (p < .001) than OMN. Mean total DASS and POMS scores were positively related to mean intakes of EPA (p < 0.05), DHA (p < 0.05), and AA (p < 0.05), and inversely related to intakes of ALA (p < 0.05), and LA (p < 0.05), indicating that participants with low intakes of EPA, DHA, and AA and high intakes of ALA and LA had better mood. Conclusions The vegetarian diet profile does not appear to adversely affect mood despite low intake of long-chain omega-3 fatty acids.",
"title": "Vegetarian diets are associated with healthy mood states: a cross-sectional study in Seventh Day Adventist adults"
},
{
"docid": "MED-5337",
"text": "PURPOSE: Men with prostate cancer are often advised to make changes in diet and lifestyle, although the impact of these changes has not been well documented. Therefore, we evaluated the effects of comprehensive lifestyle changes on prostate specific antigen (PSA), treatment trends and serum stimulated LNCaP cell growth in men with early, biopsy proven prostate cancer after 1 year. MATERIALS AND METHODS: Patient recruitment was limited to men who had chosen not to undergo any conventional treatment, which provided an unusual opportunity to have a nonintervention randomized control group to avoid the confounding effects of interventions such as radiation, surgery or androgen deprivation therapy. A total of 93 volunteers with serum PSA 4 to 10 ng/ml and cancer Gleason scores less than 7 were randomly assigned to an experimental group that was asked to make comprehensive lifestyle changes or to a usual care control group. RESULTS: None of the experimental group patients but 6 control patients underwent conventional treatment due to an increase in PSA and/or progression of disease on magnetic resonance imaging. PSA decreased 4% in the experimental group but increased 6% in the control group (p = 0.016). The growth of LNCaP prostate cancer cells (American Type Culture Collection, Manassas, Virginia) was inhibited almost 8 times more by serum from the experimental than from the control group (70% vs 9%, p <0.001). Changes in serum PSA and also in LNCaP cell growth were significantly associated with the degree of change in diet and lifestyle. CONCLUSIONS: Intensive lifestyle changes may affect the progression of early, low grade prostate cancer in men. Further studies and longer term followup are warranted.",
"title": "Intensive lifestyle changes may affect the progression of prostate cancer."
},
{
"docid": "MED-3001",
"text": "Over the last three decades, the concept of Western disease has become well established. Medicine has approached this group of diseases by searching for new cures but has achieved relatively little success. We argue that medicine should now accept the failure of this strategy and place a major emphasis on prevention. The key objective is to change the climate of opinion so that prevention is taken seriously by the general population. The chief activity should be a wide ranging public education campaign so as to persuade people to live a healthier lifestyle. Medicine will require restructuring in order to carry out this work. Medical education needs to be reformed so that medical students receive the necessary training. This must be done as part of an integrated approach in which government, industry and medical research all play a major role. Governments should use taxation and subsidies in areas such as food and tobacco so as to shift consumption patterns towards healthier products. Governments must also tighten laws on tobacco sales and advertising, support health education, and improve food labelling. Industry must be made far more responsive to the health needs of the population. This should be done both by public education, so as to alter demand, and by government action. Medical research should change its emphasis from studying the detailed mechanisms of disease (\"complex research\") to studying the role of lifestyle factors (\"simple research\").",
"title": "Towards a new system of health: the challenge of Western disease."
},
{
"docid": "MED-2997",
"text": "If disease patterns emerge which show that certain diseases can be related, this is a valuable pointer to a common cause. This article traces the principle of interpreting disease relationships, illustrated by several common conditions of western civilization, for which the common cause is postulated as being removal of fiber from the diet.",
"title": "The Etiological Significance of Related Diseases"
},
{
"docid": "MED-3206",
"text": "To study the effects of grapefruit and grapefruit products on body weight and metabolic syndrome, 91 obese patients were randomized to either placebo capsules and 7 ounces (207 mL) of apple juice, grapefruit capsules with 7 ounces (207 mL) of apple juice, 8 ounces (237 mL) of grapefruit juice with placebo capsule, or half of a fresh grapefruit with a placebo capsule three times a day before each meal. Metabolic syndrome parameters were measured at the beginning and end of 12 weeks. After 12 weeks, the fresh grapefruit group had lost 1.6 kg, the grapefruit juice group had lost 1.5 kg, the grapefruit capsule group had lost 1.1 kg, and the placebo group had lost 0.3 kg. The fresh grapefruit group lost significantly more weight than the placebo group (P < .05). A secondary analysis of those with the metabolic syndrome in the four treatment groups demonstrated a significantly greater weight loss in the grapefruit, grapefruit capsule, and grapefruit juice groups compared with placebo (P < .02). There was also a significant reduction in 2-hour post-glucose insulin level in the grapefruit group compared with placebo. Half of a fresh grapefruit eaten before meals was associated with significant weight loss. In metabolic syndrome patients the effect was also seen with grapefruit products. Insulin resistance was improved with fresh grapefruit. Although the mechanism of this weight loss is unknown it would appear reasonable to include grapefruit in a weight reduction diet.",
"title": "The effects of grapefruit on weight and insulin resistance: relationship to the metabolic syndrome."
},
{
"docid": "MED-4125",
"text": "Erythritol, a naturally occurring polyol, is gaining attention as a bulk sweetener for human nutrition. Industrially, it is produced from glucose by fermentation. From various studies it is known to be non-cariogenic. Moreover, it is rapidly absorbed in the small intestine and quantitatively excreted in the urine. Only about 10 % enters the colon. Earlier in vitro experiments showed that erythritol remained unfermented for a fermentation period of 12 h. In order to investigate whether fresh human intestinal microbiota is able to adapt its enzyme activities to erythritol, a 24 h lasting fermentation was carried out under well-standardised in vitro conditions. For comparison maltitol, lactulose and blank (faecal inoculum only) were incubated as well. Fermentation patterns were established by following total gas production, hydrogen accumulation, changes in pH value, SCFA production and substrate degradation. Taking all fermentation parameters into account, erythritol turned out to be completely resistant to bacterial attack within 24 h, thus excluding an adaptation within that period. Since under in vivo conditions more easily fermentable substrates enter the colon continuously, it seems very unlikely that erythritol will be fermented in vivo.",
"title": "Human gut microbiota does not ferment erythritol."
},
{
"docid": "MED-5330",
"text": "Although there is a well-established relation between serum cholesterol and coronary artery disease risk, individual and national variations in this association suggest that other factors are involved in atherogenesis. High-fat diet associated triglyceride-rich lipoproteins have also been suggested to be atherogenic. To assess the direct effect of postprandial triglyceride-rich lipoproteins on endothelial function, an early factor in atherogenesis--10 healthy, normocholesterolemic volunteers--were studied before and for 6 hours after single isocaloric high- and low-fat meals (900 calorie; 50 and 0 g fat, respectively). Endothelial function, in the form of flow-mediated vasoactivity, was assessed in the brachial artery using 7.5-MHz ultrasound as percent arterial diameter change 1 minute after 5 minutes of upper-arm arterial occlusion. Serum lipoproteins and glucose were determined before eating and 2 and 4 hours postprandially. Serum triglycerides increased from 94 +/- 55 mg/dl preprandially to 147 +/- 80 mg/dl 2 hours after the high-fat meal (p = 0.05). Flow-dependent vasoactivity decreased from 21 +/- 5% preprandially to 11 +/- 4%, 11 +/- 6%, and 10 +/- 3% at 2, 3, and 4 hours after the high-fat meal, respectively (all p <0.05 compared with low-fat meal data). No changes in lipoproteins or flow-mediated vasoactivity were observed after the low-fat meal. Fasting low-density lipoprotein cholesterol correlated inversely (r = -0.47, p = 0.04) with preprandial flow-mediated vasoactivity, but triglyceride level did not. Mean change in postprandial flow-mediated vasoactivity at 2, 3, and 4 hours correlated with change in 2-hour serum triglycerides (r = -0.51, p = 0.02). These results demonstrate that a single high-fat meal transiently impairs endothelial function. These findings identify a potential process by which a high-fat diet may be atherogenic independent of induced changes in cholesterol.",
"title": "Effect of a single high-fat meal on endothelial function in healthy subjects."
},
{
"docid": "MED-3203",
"text": "The contents of the bioactive compounds in red and blond grapefruits and their influence on humans suffering from hypertriglyceridemia were studied. It was found that red grapefruit has a higher content of bioactive compounds and a higher antioxidant potential than blond grapefruit, determined by oxygen radical scavenging capacity, 1,1-diphenyl-2-picrylhydrazyl, carotenoid bleaching, and Folin-Ciocalteu assays. Fifty-seven hyperlipidemic patients, ages 39-72 years, after coronary bypass surgery, recruited from the Institute's pool of volunteers, were randomly divided into three equal in number (19) groups: two experimental (red and blond groups) and one control group (CG). During 30 consecutive days of the investigation the diets of the patients of the red and blond dietary groups were daily supplemented with one equal in weight fresh red or blond grapefruit, respectively. Before and after this trial, serum lipid levels of all fractions and serum antioxidant activity were determined. It was found that serum lipid levels in patients of the red and blond groups versus the CG after treatment were decreased: (a) total cholesterol, 6.69 versus 7.92 mmol/L, 15.5%, and 7.32 versus 7.92 mmol/L, 7.6%, respectively; (b) low-density lipoprotein cholesterol, 5.01 versus 6.29 mmol/L, 20.3%, and 5.62 versus 6.29 mmol/L, 10.7%, respectively; (c) triglycerides, 1.69 versus 2.32 mmol/L, 17.2%, and 2.19 versus 2.32 mmol/L, 5.6%, respectively. No changes in the serum lipid levels in patients of the CG were found. In conclusion, fresh red grapefruit contains higher quantities of bioactive compounds and has significantly higher antioxidant potential than blond grapefruit. Diet supplemented with fresh red grapefruit positively influences serum lipid levels of all fractions, especially serum triglycerides and also serum antioxidant activity. The addition of fresh red grapefruit to generally accepted diets could be beneficial for hyperlipidemic, especially hypertriglyceridemic, patients suffering from coronary atherosclerosis.",
"title": "Red grapefruit positively influences serum triglyceride level in patients suffering from coronary atherosclerosis: studies in vitro and in humans."
},
{
"docid": "MED-4157",
"text": "Although improvement in long-term health is no longer an indication for menopausal hormone therapy, evidence supporting fewer adverse events in younger women, combined with its high overall effectiveness, has reinforced its usefulness for short-term treatment of menopausal symptoms. Menopausal therapy has been provided not only by commercially available products but also by compounding, or creation of an individualized preparation in response to a health care provider's prescription to create a medication tailored to the specialized needs of an individual patient. The Women's Health Initiative findings, coupled with an increase in the direct-to-consumer marketing and media promotion of compounded bioidentical hormonal preparations as safe and effective alternatives to conventional menopausal hormone therapy, have led to a recent increase in the popularity of compounded bioidentical hormones as well as an increase in questions about the use of these preparations. Not only is evidence lacking to support superiority claims of compounded bioidentical hormones over conventional menopausal hormone therapy, but these claims also pose the additional risks of variable purity and potency and lack efficacy and safety data. The Committee on Gynecologic Practice of the American College of Obstetricians and Gynecologists and the Practice Committee of the American Society for Reproductive Medicine provide an overview of the major issues of concern surrounding compounded bioidentical menopausal hormone therapy and provide recommendations for patient counseling. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.",
"title": "Compounded bioidentical menopausal hormone therapy."
},
{
"docid": "MED-5325",
"text": "Objective Previous work studying vegetarians has often found that they have lower blood pressure (BP). Reasons may include their lower BMI and higher intake levels of fruit and vegetables. Here we seek to extend this evidence in a geographically diverse population containing vegans, lacto-ovo vegetarians and omnivores. Design Data are analysed from a calibration sub-study of the Adventist Health Study-2 (AHS-2) cohort who attended clinics and provided validated FFQ. Criteria were established for vegan, lacto-ovo vegetarian, partial vegetarian and omnivorous dietary patterns. Setting Clinics were conducted at churches across the USA and Canada. Dietary data were gathered by mailed questionnaire. Subjects Five hundred white subjects representing the AHS-2 cohort. Results Covariate-adjusted regression analyses demonstrated that the vegan vegetarians had lower systolic and diastolic BP (mmHg) than omnivorous Adventists (β =−6·8, P<0·05 and β = −6·9, P<0·001). Findings for lacto-ovo vegetarians (β = −9·1, P<0·001 and β = −5·8, P<0·001) were similar. The vegetarians (mainly the vegans) were also less likely to be using antihypertensive medications. Defining hypertension as systolic BP > 139 mmHg or diastolic BP > 89 mmHg or use of antihypertensive medications, the odds ratio of hypertension compared with omnivores was 0·37 (95 % CI 0·19, 0·74), 0·57 (95 % CI 0·36, 0·92) and 0·92 (95 % CI 0·50, 1·70), respectively, for vegans, lacto-ovo vegetarians and partial vegetarians. Effects were reduced after adjustment for BMI. Conclusions We conclude from this relatively large study that vegetarians, especially vegans, with otherwise diverse characteristics but stable diets, do have lower systolic and diastolic BP and less hypertension than omnivores. This is only partly due to their lower body mass.",
"title": "Vegetarian diets and blood pressure among white subjects: results from the Adventist Health Study-2 (AHS-2)"
},
{
"docid": "MED-3209",
"text": "The effects of grapefruit juice on the bioavailability of 17 alpha-ethinylestradiol (EE2) after a single oral administration of 50 micrograms EE2 have been investigated. The pharmacokinetics of EE2 were studied in an open, randomized, cross-over study in which 13 healthy volunteers were administered the drug with herbal tea or grapefruit juice (naringin, 887 mg/ml). In contrast to herbal tea, grapefruit juice increased the peak plasma concentration (Cmax) significantly to 137% (mean; range 64% to 214%, p = 0.0088) and increased the area under plasma concentration-time curve from 0 to 8 hours (AUC0-8) to 128% (mean; range 81% to 180%, p = 0.0186). This study shows that grapefruit juice increases the bioavailable amount of EE2. A possible explanation may be that grapefruit juice inhibits the metabolic degradation of EE2. Whether the increased bioavailability of EE2 following grapefruit juice administration is of clinical importance should be investigated in long-term studies.",
"title": "Can grapefruit juice influence ethinylestradiol bioavailability?"
},
{
"docid": "MED-5328",
"text": "Aim To evaluate the relationship of diet to incident diabetes among non-Black and Black participants in the Adventist Health Study-2. Methods and Results Participants were 15,200 men and 26,187 women (17.3% Blacks) across the U.S. and Canada who were free of diabetes and who provided demographic, anthropometric, lifestyle and dietary data. Participants were grouped as vegan, lacto ovo vegetarian, pesco vegetarian, semi-vegetarian or non-vegetarian (reference group). A follow-up questionnaire after two years elicited information on the development of diabetes. Cases of diabetes developed in 0.54% of vegans, 1.08% of lacto ovo vegetarians, 1.29% of pesco vegetarians, 0.92% of semi-vegetarians and 2.12% of non-vegetarians. Blacks had an increased risk compared to non-Blacks (odds ratio [OR] 1.364; 95% confidence interval [CI], 1.093–1.702). In multiple logistic regression analysis controlling for age, gender, education, income, television watching, physical activity, sleep, alcohol use, smoking and BMI, vegans (OR 0.381; 95% CI 0.236–0.617), lacto ovo vegetarians (OR 0.618; 95% CI 0.503–0.760) and semi-vegetarians (OR 0.486, 95% CI 0.312–0.755) had a lower risk of diabetes than non-vegetarians. In non-Blacks vegan, lacto ovo and semi-vegetarian diets were protective against diabetes (OR 0.429, 95% CI 0.249–0.740; OR 0.684, 95% CI 0.542–0.862; OR 0.501, 95% CI 0.303–0.827); among Blacks vegan and lacto ovo vegetarian diets were protective (OR 0.304, 95% CI 0.110–0.842; OR 0.472, 95% CI 0.270–0.825). These associations were strengthened when BMI was removed from the analyses. Conclusion Vegetarian diets (vegan, lacto ovo, semi-) were associated with a substantial and independent reduction in diabetes incidence. In Blacks the dimension of the protection associated with vegetarian diets was as great as the excess risk associated with Black ethnicity.",
"title": "Vegetarian diets and incidence of diabetes in the Adventist Health Study-2"
},
{
"docid": "MED-5323",
"text": "This study reviewed the literature on the relations between exposure to chemicals with endocrine-disrupting abilities and obesity in humans. The studies generally indicated that exposure to some of the endocrine-disrupting chemicals was associated with an increase in body size in humans. The results depended on the type of chemical, exposure level, timing of exposure and gender. Nearly all the studies investigating dichlorodiphenyldichloroethylene (DDE) found that exposure was associated with an increase in body size, whereas the results of the studies investigating polychlorinated biphenyl (PCB) exposure were depending on dose, timing and gender. Hexachlorobenzene, polybrominated biphenyls, beta-hexachlorocyclohexane, oxychlordane and phthalates were likewise generally associated with an increase in body size. Studies investigating polychlorinated dibenzodioxins and polychlorinated dibenzofurans found either associations with weight gain or an increase in waist circumference, or no association. The one study investigating relations with bisphenol A found no association. Studies investigating prenatal exposure indicated that exposure in utero may cause permanent physiological changes predisposing to later weight gain. The study findings suggest that some endocrine disruptors may play a role for the development of the obesity epidemic, in addition to the more commonly perceived putative contributors. © 2011 The Authors. obesity reviews © 2011 International Association for the Study of Obesity.",
"title": "Endocrine-disrupting chemicals and obesity development in humans: a review."
},
{
"docid": "MED-5331",
"text": "A global health transition is currently underway. The burden of non-communicable diseases (NCDs) is increasing rapidly in the developing world, very much as a result of changes in lifestyles. In addition to changes in tobacco use and physical activity, major changes are taking place in diets, contributing greatly to the growing epidemic of NCD. Thus, a huge global public health challenge is how to influence the trends in diet and nutrition for effective global NCD prevention. The health transition took place rapidly in Finland after World War II and mortality from cardiovascular disease (CVD) was exceptionally high. The North Karelia Project was launched in 1972 as a community-based, and later as a national, programme to influence diet and other lifestyles that are crucial in the prevention of CVD. The intervention had a strong theory base and it employed comprehensive strategies. Broad community organisation and the strong participation of people were the key elements. Evaluation has shown how the diet (particularly fat consumption) has changed and how these changes have led to a major reduction in population serum cholesterol and blood pressure levels. It has also shown how ischaemic heart disease mortality in a working-age population has declined by 73% in North Karelia and by 65% in the whole country from 1971 to 1995. Although Finland is an industrialised country, North Karelia was rural, of rather low socio-economic level and with many social problems in the 1970s and 1980s. The project was based on low-cost intervention activities, where people's participation and community organisations played a key role. Comprehensive interventions in the community were eventually supported by national activities--from expert guidelines and media activities to industry collaboration and policy. Similar principles for nutrition intervention programmes could be used in developing countries, obviously tailored to the local conditions. This paper discusses the experiences of the North Karelia Project in the light of needs from the less-industrialised countries and makes some general recommendations.",
"title": "Influencing public nutrition for non-communicable disease prevention: from community intervention to national programme--experiences from Finland."
},
{
"docid": "MED-5363",
"text": "OBJECTIVE: Although several studies have reported associations of depressive state with specific nutrients and foods, few studies examined the association with dietary patterns in adults. We investigated the association between major dietary patterns and depressive symptoms in Japanese. METHODS: Subjects were 521 municipal employees (309 men and 212 women), aged 21-67 years, who participated in a health survey at the time of periodic checkup. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) Scale. Dietary patterns were derived by using principal component analysis of the consumption of 52 food and beverage items, which was assessed by a validated brief diet history questionnaire. Logistic regression analysis was used to estimate odds ratios of depressive symptoms (CES-D >or=16) with adjustment for potential confounding variables. RESULTS: We identified three dietary patterns. A healthy Japanese dietary pattern characterized by high intakes of vegetables, fruit, mushrooms and soy products was associated with fewer depressive symptoms. The multivariate-adjusted odds ratios (95% confidence intervals) of having depressive symptoms for the lowest through highest tertiles of the healthy Japanese dietary pattern score were 1.00 (reference), 0.99 (0.62-1.59) and 0.44 (0.25-0.78), respectively (P for trend=0.006). Other dietary patterns were not appreciably associated with depressive symptoms. CONCLUSIONS: Our findings suggest that a healthy Japanese dietary pattern may be related to decreased prevalence of depressive status.",
"title": "Dietary patterns and depressive symptoms among Japanese men and women."
},
{
"docid": "MED-3205",
"text": "Grapefruit inhibits cytochrome P450 3A4 and may affect estrogen metabolism. In the European Prospective Investigation into Cancer and Nutrition (EPIC), we examined the relationships of grapefruit intake with risk of breast cancer and with serum sex hormone levels. 114,504 women with information on dietary intake of grapefruit and on reproductive and lifestyle risk factors were followed for a median 9.5 years and 3,747 incident breast cancers were identified. Fifty-nine percent of women reported eating grapefruit, 4% ate > or = 60 g/day. Cox proportional hazard models were used to estimate the hazard ratio (HR) for breast cancer according to grapefruit intake, adjusting for study centre, reproductive factors, body mass index, energy intake, and alcohol intake. Grapefruit intake was not related to the risk of breast cancer: compared with women who ate no grapefruit, women with the highest intake of > or =60 g/day had a HR of 0.93 (95% CI 0.77-1.13), p for linear trend = 0.5. There was no relationship between grapefruit intake and breast cancer risk among premenopausal women, all postmenopausal women, or postmenopausal women categorized by hormone replacement therapy use (all p>0.05). There was no association between grapefruit intake and estradiol or estrone among postmenopausal women. In this study, we found no evidence of an association between grapefruit intake and risk of breast cancer.",
"title": "Prospective study of the association between grapefruit intake and risk of breast cancer in the European Prospective Investigation into Cancer and ..."
},
{
"docid": "MED-5340",
"text": "In Asia, vegetarianism is a well-established eating behavior. It appears that the adoption of a vegan diet leads to a lessening of several health risk factors. Although vegetarianism has some notable effects on the hematological system, the effect on the nephrological system has not been well clarified. The pattern of renal function parameters was studied in 25 Thai vegans compared with 25 non-vegetarians. Of the studied parameters, it was found that urine protein was significantly different (p < 0.05) in vegans and controls. Vegans had significantly lower urine protein level.",
"title": "Renal function parameters of Thai vegans compared with non-vegans."
},
{
"docid": "MED-2999",
"text": "Many of the commonest diseases in the economically more developed communities are characteristic of modern Western culture. Evidence is presented suggesting that they represent a failure of adaptation to the dramatic changes in diet that have been associated with the emergence of modern Western culture. Dietary changes aimed at the alleviation and prevention of these diseases are discussed and recommended.",
"title": "Western diseases and their emergence related to diet."
},
{
"docid": "MED-5333",
"text": "BACKGROUND/AIM: A vegetarian diet is known to prevent a series of diseases but may influence the balance of carbohydrate and fat metabolism as well as collagen synthesis. This study compares expression patterns of relevant genes in oral mucosa of omnivores and vegetarians. METHODS: Quantitative reverse transcriptase polymerase chain reaction was applied for analysis of mRNA levels from carnitine transporter OCTN2, hepatic CPT1A and nonhepatic CPT1B isoforms of carnitine palmitoyltransferase and collagen (CCOL2A1) in oral mucosa. RESULTS: Compared with volunteers with traditional eating habits, carbohydrate consumption was significantly higher (+22%) in vegetarians. This was associated with a significant stimulation of CPT1A (+50%) and OCTN2 (+10%) and a lowered collagen synthesis (-10%). CONCLUSION: These novel findings provide further insight into the association of a changed fat metabolism and reduced collagen synthesis in vegetarians, which could also play a role in the aging process. Copyright 2008 S. Karger AG, Basel.",
"title": "Vegetarian diet affects genes of oxidative metabolism and collagen synthesis."
},
{
"docid": "MED-4829",
"text": "BACKGROUND: Statin therapy can cause myopathy, however it is unclear whether this exacerbates age-related muscle function declines. AIM: To describe differences between statin users and non-users in muscle mass, muscle function and falls risk in a group of community-dwelling older adults. DESIGN: A prospective, population-based cohort study with a mean follow-up of 2.6 years. METHODS: Total 774 older adults [48% female; mean (standard deviation) age = 62 (7) years] were examined at baseline and follow-up. Differences in percentage appendicular lean mass (%ALM), leg strength, leg muscle quality (LMQ; specific force) and falls risk were compared for statin users and non-users. RESULTS: There were 147 (19%) statin users at baseline and 179 (23%) at follow-up. Longitudinal analyses revealed statin use at baseline predicted increased falls risk scores over 2.6 years (0.14, 95% CI 0.01 to 0.27) and a trend towards increased %ALM (0.45%, 95% CI -0.01 to 0.92). Statin users at both time points demonstrated decreased leg strength (-5.02 kg, 95% CI -9.65 to -0.40) and LMQ (-0.30 kg/kg, 95% CI -0.59 to -0.01), and trended towards increased falls risk (0.13, 95% CI -0.01 to 0.26) compared to controls. Finally, statin users at both baseline and follow-up demonstrated decreased leg strength (-16.17 kg, 95% CI -30.19 to -2.15) and LMQ (-1.13 kg/kg, 95% CI -2.02 to -0.24) compared to those who had ceased statin use at follow-up. CONCLUSION: Statin use may exacerbate muscle performance declines and falls risk associated with aging without a concomitant decrease in muscle mass, and this effect may be reversible with cessation.",
"title": "Statin therapy, muscle function and falls risk in community-dwelling older adults."
},
{
"docid": "MED-5332",
"text": "The gastrointestinal microbiota produces short-chain fatty acids, especially butyrate, which affect colonic health, immune function and epigenetic regulation. To assess the effects of nutrition and aging on the production of butyrate, the butyryl-CoA:acetate CoA-transferase gene and population shifts of Clostridium clusters lV and XlVa, the main butyrate producers, were analysed. Faecal samples of young healthy omnivores (24 ± 2.5 years), vegetarians (26 ± 5 years) and elderly (86 ± 8 years) omnivores were evaluated. Diet and lifestyle were assessed in questionnaire-based interviews. The elderly had significantly fewer copies of the butyryl-CoA:acetate CoA-transferase gene than young omnivores (P=0.014), while vegetarians showed the highest number of copies (P=0.048). The thermal denaturation of the butyryl-CoA:acetate CoA-transferase gene variant melting curve related to Roseburia/Eubacterium rectale spp. was significantly more variable in the vegetarians than in the elderly. The Clostridium cluster XIVa was more abundant in vegetarians (P=0.049) and in omnivores (P<0.01) than in the elderly group. Gastrointestinal microbiota of the elderly is characterized by decreased butyrate production capacity, reflecting increased risk of degenerative diseases. These results suggest that the butyryl-CoA:acetate CoA-transferase gene is a valuable marker for gastrointestinal microbiota function. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.",
"title": "Quantification of butyryl CoA:acetate CoA-transferase genes reveals different butyrate production capacity in individuals according to diet and age."
},
{
"docid": "MED-5334",
"text": "Until recently, intact protein that is rich in tryptophan was not seen as an alternative to pharmaceutical-grade tryptophan because protein also contains large neutral amino acids (LNAAs) that compete for transport sites across the blood-brain barrier. Recent evidence indicates that when deoiled gourd seed (a rich source of tryptophan with approximately 22 mg/g protein) is combined with glucose (a carbohydrate that reduces serum levels of competing LNAAs) a clinical effect similar to that of pharmaceutical-grade tryptophan is achieved. Objective and subjective measures of anxiety in those suffering from social phobia (also known as social anxiety disorder) were employed to measure changes in anxiety in response to a stimulus as part of a double-blind, placebo-controlled, crossover study with a wash-out period of 1 week between study sessions. Subjects were randomly assigned to start with either (i) protein-source tryptophan (deoiled gourd seed) in combination with carbohydrate or (ii) carbohydrate alone. One week after the initial session, subjects returned for a follow-up session and received the opposite treatment of that received at the first session. All 7 subjects who began the study completed the 2-week protocol. Protein-source tryptophan with carbohydrate, but not carbohydrate alone, resulted in significant improvement on an objective measure of anxiety. Protein-source tryptophan combined with a high glycemic carbohydrate is a potential anxiolytic to those suffering from social phobia.",
"title": "Protein-source tryptophan as an efficacious treatment for social anxiety disorder: a pilot study."
},
{
"docid": "MED-4162",
"text": "Large numbers of US women stopped taking hormone therapies (HT), especially estrogen/progestin (EP) formulations, after the Women's Health Initiative trial detected elevated risks of breast cancer in EP users and was halted in July 2002. Recent reports have indicated substantial and significant declines in population-based breast cancer incidence, particularly hormone-sensitive forms, for 2003 and 2004. Are these events linked? This commentary considers the available evidence linking the mass cessation of HT in 2002 to the breast cancer incidence declines of 2003/2004 and quantifies the potential impact of the cessation on the overall burden of breast cancer in the US.",
"title": "Declines in breast cancer after the WHI: apparent impact of hormone therapy."
},
{
"docid": "MED-3199",
"text": "It has been well established that complex mixtures of phytochemicals in fruits and vegetables can be beneficial for human health. Moreover, it is becoming increasingly apparent that phytochemicals can influence the pharmacological activity of drugs by modifying their absorption characteristics through interactions with drug transporters as well as drug-metabolizing enzyme systems. Such effects are more likely to occur in the intestine and liver, where high concentrations of phytochemicals may occur. Alterations in cytochrome P450 and other enzyme activities may influence the fate of drugs subject to extensive first-pass metabolism. Although numerous studies of nutrient-drug interactions have been published and systematic reviews and meta-analyses of these studies are available, no generalizations on the effect of nutrient-drug interactions on drug bioavailability are currently available. Several publications have highlighted the unintended consequences of the combined use of nutrients and drugs. Many phytochemicals have been shown to have pharmacokinetic interactions with drugs. The present review is limited to commonly consumed fruits and vegetables with significant beneficial effects as nutrients and components in folk medicine. Here, we discuss the phytochemistry and pharmacokinetic interactions of the following fruit and vegetables: grapefruit, orange, tangerine, grapes, cranberry, pomegranate, mango, guava, black raspberry, black mulberry, apple, broccoli, cauliflower, watercress, spinach, tomato, carrot, and avocado. We conclude that our knowledge of the potential risk of nutrient-drug interactions is still limited. Therefore, efforts to elucidate potential risks resulting from food-drug interactions should be intensified in order to prevent undesired and harmful clinical consequences. © 2011 Institute of Food Technologists®",
"title": "Potential risks resulting from fruit/vegetable-drug interactions: effects on drug-metabolizing enzymes and drug transporters."
},
{
"docid": "MED-4159",
"text": "CONTEXT: The Women's Health Initiative Memory Study (WHIMS) previously found increased risk for dementia and no effect on mild cognitive impairment (MCI) in women treated with conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA). OBJECTIVE: To determine the effects of CEE alone and CEE plus MPA on incidence of probable dementia and MCI in older women. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled clinical trials of CEE (estrogen-alone trial) or CEE plus MPA (estrogen plus progestin trial) in community-dwelling women aged 65 to 79 years, conducted from June 1995 to July 8, 2002 (estrogen plus progestin; n = 4532), or to February 29, 2004 (estrogen-alone; n = 2947), in 39 of the 40 WHI clinical centers. INTERVENTIONS: In the estrogen-alone trial, 1 daily tablet containing either 0.625 mg/d of CEE vs matching placebo; in the estrogen plus progestin trial, 1 daily tablet containing CEE (0.625 mg/d) plus MPA (2.5 mg/d) vs matching placebos. MAIN OUTCOME MEASURES: Probable dementia and MCI. RESULTS: In the estrogen-alone trial, 47 participants were diagnosed with probable dementia, of whom 28 were assigned to CEE and 19 to placebo (hazard ratio [HR], 1.49; 95% confidence interval [CI], 0.83-2.66). Incidence rates for probable dementia in the estrogen-alone trial were statistically similar to those in the estrogen plus progestin trial (45 vs 22 per 10 000 person-years for CEE plus MPA vs placebo, respectively; P =.11). When data were pooled per the original WHIMS protocol, the overall HR for probable dementia was 1.76 (95% CI, 1.19-2.60; P =.005). After excluding participants with baseline Modified Mini-Mental State Examination scores at or below the screening cut point, the HR was 1.77 (95% CI, 0.74-4.23; P =.20) in the estrogen-alone trial and 2.19 (95% CI, 1.25-3.84; P =.006) in the pooled trials. In the estrogen-alone trial, 76 participants were diagnosed with MCI in the CEE group vs 58 in the placebo group (HR, 1.34; 95% CI, 0.95-1.89). In the combined trial data, the HR was similar (1.25; 95% CI, 0.97-1.60). In the estrogen-alone trial, 93 participants receiving CEE were diagnosed with either probable dementia or MCI vs 69 receiving placebo (HR, 1.38; 95% CI, 1.01-1.89; P =.04). CONCLUSIONS: Estrogen therapy alone did not reduce dementia or MCI incidence and increased the risk for both end points combined. Pooling data for estrogen alone and estrogen plus progestin resulted in increased risks for both end points. Use of hormone therapy to prevent dementia or cognitive decline in women 65 years of age or older is not recommended.",
"title": "Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women's Health Initiative Mem..."
},
{
"docid": "MED-4127",
"text": "We report for the first time an unusual musculoskeletal adverse effect of aspartame in two patients. A 50-year-old woman had been suffering from widespread pain and fatigue for more than 10 years leading to the diagnosis of fibromyalgia. During a vacation in a foreign country, she did not suffer from painful symptoms since she had forgotten to take her aspartame. All of the symptoms reappeared in the days following her return when she reintroduced aspartame into her daily diet. Thus, aspartame was definitively excluded from her diet, resulting in a complete regression of the fibromyalgia symptoms. A 43-year-old man consulted for a 3-year history of bilateral forearm, wrist, and hand and cervical pain with various unsuccessful treatments. A detailed questioning allowed to find out that he had been taking aspartame for three years. The removal of aspartame was followed by a complete regression of pain, without recurrence. We believe that these patients' chronic pain was due to the ingestion of aspartame, a potent flavouring agent, widely used in food as a calorie-saver. The benefit/ risk ratio of considering the diagnosis of aspartame-induced chronic pain is obvious: the potential benefit is to cure a disabling chronic disease, to spare numerous laboratory and imaging investigations, and to avoid potentially harmful therapies; the potential risk is to temporarily change the patient's diet. Thus, practitioners should ask patients suffering from fibromyalgia about their intake of aspartame. In some cases, this simple question might lead to the resolution of a disabling chronic disease.",
"title": "Aspartame-induced fibromyalgia, an unusual but curable cause of chronic pain."
},
{
"docid": "MED-4828",
"text": "Background Many patients taking statins often complain of muscle pain and weakness. The extent to which muscle pain reflects muscle injury is unknown. Methods We obtained biopsy samples from the vastus lateralis muscle of 83 patients. Of the 44 patients with clinically diagnosed statin-associated myopathy, 29 were currently taking a statin, and 15 had discontinued statin therapy before the biopsy (minimal duration of discontinuation 3 weeks). We also included 19 patients who were taking statins and had no myopathy, and 20 patients who had never taken statins and had no myopathy. We classified the muscles as injured if 2% or more of the muscle fibres in a biopsy sample showed damage. Using reverse transcriptase polymerase chain reaction, we evaluated the expression levels of candidate genes potentially related to myocyte injury. Results Muscle injury was observed in 25 (of 44) patients with myopathy and in 1 patient without myopathy. Only 1 patient with structural injury had a circulating level of creatine phosphokinase that was elevated more than 1950 U/L (10× the upper limit of normal). Expression of ryanodine receptor 3 was significantly upregulated in patients with biopsy evidence of structural damage (1.7, standard error of the mean 0.3). Interpretation Persistent myopathy in patients taking statins reflects structural muscle damage. A lack of elevated levels of circulating creatine phosphokinase does not rule out structural muscle injury. Upregulation of the expression of ryanodine receptor 3 is suggestive of an intracellular calcium leak.",
"title": "Association between statin-associated myopathy and skeletal muscle damage"
},
{
"docid": "MED-5326",
"text": "The effect of meat consumption on cancer risk is a controversial issue. However, recent meta-analyses show that high consumers of cured meats and red meat are at increased risk of colorectal cancer. This increase is significant but modest (20-30%). Current WCRF-AICR recommendations are to eat no more than 500 g per week of red meat, and to avoid processed meat. Moreover, our studies show that beef meat and cured pork meat promote colon carcinogenesis in rats. The major promoter in meat is heme iron, via N-nitrosation or fat peroxidation. Dietary additives can suppress the toxic effects of heme iron. For instance, promotion of colon carcinogenesis in rats by cooked, nitrite-treated and oxidized high-heme cured meat was suppressed by dietary calcium and by α-tocopherol, and a study in volunteers supported these protective effects in humans. These additives, and others still under study, could provide an acceptable way to prevent colorectal cancer. Copyright © 2011 Elsevier B.V. All rights reserved.",
"title": "Red meat and colon cancer: should we become vegetarians, or can we make meat safer?"
},
{
"docid": "MED-4830",
"text": "Muscle pain and weakness are frequent complaints in patients receiving 3-hydroxymethylglutaryl coenzymeA (HMG CoA) reductase inhibitors (statins). Many patients with myalgia have creatine kinase levels that are either normal or only marginally elevated, and no obvious structural defects have been reported in patients with myalgia only. To investigate further the mechanism that mediates statin-induced skeletal muscle damage, skeletal muscle biopsies from statin-treated and non-statin-treated patients were examined using both electron microscopy and biochemical approaches. The present paper reports clear evidence of skeletal muscle damage in statin-treated patients, despite their being asymptomatic. Though the degree of overall damage is slight, it has a characteristic pattern that includes breakdown of the T-tubular system and subsarcolemmal rupture. These characteristic structural abnormalities observed in the statin-treated patients were reproduced by extraction of cholesterol from skeletal muscle fibres in vitro. These findings support the hypothesis that statin-induced cholesterol lowering per se contributes to myocyte damage and suggest further that it is the specific lipid/protein organization of the skeletal muscle cell itself that renders it particularly vulnerable. Copyright (c) 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.",
"title": "Statin therapy induces ultrastructural damage in skeletal muscle in patients without myalgia."
},
{
"docid": "MED-5338",
"text": "Summary Background and objectives Patients with advanced chronic kidney disease (CKD) are in positive phosphorus balance, but phosphorus levels are maintained in the normal range through phosphaturia induced by increases in fibroblast growth factor-23 (FGF23) and parathyroid hormone (PTH). This provides the rationale for recommendations to restrict dietary phosphate intake to 800 mg/d. However, the protein source of the phosphate may also be important. Design, setting, participants, & measurements We conducted a crossover trial in nine patients with a mean estimated GFR of 32 ml/min to directly compare vegetarian and meat diets with equivalent nutrients prepared by clinical research staff. During the last 24 hours of each 7-day diet period, subjects were hospitalized in a research center and urine and blood were frequently monitored. Results The results indicated that 1 week of a vegetarian diet led to lower serum phosphorus levels and decreased FGF23 levels. The inpatient stay demonstrated similar diurnal variation for blood phosphorus, calcium, PTH, and urine fractional excretion of phosphorus but significant differences between the vegetarian and meat diets. Finally, the 24-hour fractional excretion of phosphorus was highly correlated to a 2-hour fasting urine collection for the vegetarian diet but not the meat diet. Conclusions In summary, this study demonstrates that the source of protein has a significant effect on phosphorus homeostasis in patients with CKD. Therefore, dietary counseling of patients with CKD must include information on not only the amount of phosphate but also the source of protein from which the phosphate derives.",
"title": "Original Articles: Vegetarian Compared with Meat Dietary Protein Source and Phosphorus Homeostasis in Chronic Kidney Disease"
},
{
"docid": "MED-4124",
"text": "OBJECTIVE: Hyperglycemia, oxidative stress, and the onset and progression of diabetic complications are strongly linked. Reduction of oxidative stress could be of utmost importance in the long-term treatment of diabetic patients. The chronic nature of the disease calls for a mode of antioxidant intake that can be sustained easily, e.g., by the diet. Erythritol, a simple polyol, could be such a compound. It is orally available, well tolerated, and its chemical structure resembles that of mannitol, a well-known hydroxyl radical (HO*) scavenger. METHODS: We studied the antioxidant properties of erythritol in vitro and subsequently determined its antioxidant activity and its vasoprotective effect in the streptozotocin diabetic rat. RESULTS: Erythritol was shown to be an excellent HO* radical scavenger and an inhibitor of 2,2'-azobis-2-amidinopropane dihydrochloride-induced hemolysis but inert toward superoxide radicals. High-performance liquid chromatographic and electron spin resonance spectroscopy studies showed that the reaction of erythritol with hydroxyl radicals resulted in the formation of erythrose and erythrulose by abstraction of a carbon-bound hydrogen atom. In the streptozotocin diabetic rat, erythritol displayed an endothelium-protective effect and, in accordance with the in vitro experiments, erythrose was found in the urine of erythritol-consuming rats. CONCLUSION: Erythritol acts as an antioxidant in vivo and may help protect against hyperglycemia-induced vascular damage. Copyright 2010 Elsevier Inc. All rights reserved.",
"title": "Erythritol is a sweet antioxidant."
},
{
"docid": "MED-398",
"text": "Summary Grapefruit is a popular, tasty and nutritive fruit enjoyed globally. Biomedical evidence in the last 10 years has, however, shown that consumption of grapefruit or its juice is associated with drug interactions, which, in some cases, have been fatal. Grapefruit-induced drug interactions are unique in that the cytochrome P450 enzyme CYP3A4, which metabolises over 60% of commonly prescribed drugs as well as other drug transporter proteins such as P-glycoprotein and organic cation transporter proteins, which are all expressed in the intestines, are involved. However, the extent to which grapefruit–drug interactions impact on clinical settings has not been fully determined, probably because many cases are not reported. It has recently emerged that grapefruit, by virtue of its rich flavonoid content, is beneficial in the management of degenerative diseases such as diabetes and cardiovascular disorders. This potentially explosive subject is reviewed here.",
"title": "The grapefruit: an old wine in a new glass? Metabolic and cardiovascular perspectives"
}
] |
[
{
"docid": "MED-3384",
"text": "OBJECTIVE: To describe trends in outpatient prescription drug utilization in US children and the changes in major areas of pediatric therapeutic use for the years 2002 through 2010. METHODS: Large prescription databases (the IMS Vector One: National and Total Patient Tracker) were used to examine national drug utilization patterns for the US pediatric population (ages 0-17 years) from 2002 through 2010. RESULTS: In 2010, a total of 263.6 million prescriptions were dispensed to the US pediatric population, 7% lower than in 2002, while prescriptions dispensed to the adult population increased 22% during the same time. Analysis of pediatric drug utilization trends for the top 12 therapeutic areas in 2010 compared with 2002 showed decreases in systemic antibiotics (-14%), allergies (-61%), pain (-14%), depression (-5%), and cough/cold without expectorant (-42%) prescriptions, whereas asthma (14%), attention-deficit/hyperactivity disorder (46%), and contraceptive (93%) prescriptions increased. In 2010, amoxicillin was the most frequently dispensed prescription in infants (aged 0-23 months) and children (aged 2-11 years). Methylphenidate was the top prescription dispensed to adolescents (aged 12-17 years). Off-label use was identified, particularly for lansoprazole; ~358,000 prescriptions were dispensed in 2010 for infants <1 year old. CONCLUSIONS: Changes in the patterns of pediatric drug utilization were observed from 2002 to 2010. Changes include a decrease in antibiotic use and an increase in attention-deficit/hyperactivity disorder medication use during the examined time. This article provides an overview of pediatric outpatient drug utilization, which could set the stage for further in-depth analyses.",
"title": "Trends of outpatient prescription drug utilization in US children, 2002-2010."
},
{
"docid": "MED-2527",
"text": "BACKGROUND: One of the major issues in controlling serum cholesterol through dietetic intervention appears to be the need to improve patient adherence. AIMS: To explore the many questions regarding barriers to, and motivators for, cholesterol-lowering diet adherence. METHODS: We surveyed French general practitioners' dietetic practices for patients with hypercholesterolaemia, and looked at their patients' attitudes towards such an approach. RESULTS: We analysed 234 doctors' personal questionnaires and 356 patient self-survey questionnaires. Patients' reasons for not complying with the prescribed diet included: 'already having satisfactory food habits' (34.7%), 'unwillingness to suffer nutritional deprivation' (33.3%), 'difficulties to conciliate a diet with family life' (27.8%) and 'taking cholesterol-lowering drugs' (22.2%). Despite a generally good understanding by patients of doctors' recommendations, some discrepancies were seen between their respective declarations. While doctors largely thought that patients needed more explanation on why and how a diet can lower cholesterol (and avoid taking drugs), only 39.4% of patients declared needing this kind of information. Other discrepancies were observed concerning barriers to, and motivators for, patient adherence. Moreover, some dietetic rules appeared to be more difficult to comply with than others, e.g. 82.6% patients remembered they should 'eat more fish' but only 51.3% actually did so. Finally, physicians, as well as patients, displayed a lack of confidence in lipid-lowering diet efficiency. CONCLUSION: Improving patient education, especially concerning their perception of risk, as well as increasing the involvement of dieticians, are motivators to explore in order to improve adherence. Copyright © 2012 Elsevier Masson SAS. All rights reserved.",
"title": "Cross-analysis of dietary prescriptions and adherence in 356 hypercholesterolaemic patients."
},
{
"docid": "MED-2281",
"text": "Nonaspirin, nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most frequently used drugs in many countries. Use of the majority of NSAIDs increases with age, primarily for symptoms associated with osteoarthritis and other chronic musculoskeletal conditions. Population-based studies have shown that, on any given day, 10-20% of elderly people (> or = 65 years old) have a current or recent NSAID prescription. Over a 6-month period in Alberta, Canada, 27% of elderly people were prescribed NSAIDs. Furthermore, in Tennessee (USA), 40% of elderly people received at least one NSAID prescription annually, and 6% had NSAID prescriptions for > 75% of the year. NSAIDs cause a wide variety of side-effects. The most clinically important side-effects are upper gastrointestinal tract dyspepsia, peptic ulceration, hemorrhage, and perforation, leading to death in some patients. Gastrointestinal side-effects are common; the most common NSAID-associated side-effect is epigastric pain/indigestion. Gastrointestinal side-effects are also a frequent reason both for withdrawal of NSAIDs and for co-treatment with another drug. Indeed, in two population-based studies of people aged > or = 65 years, the use of agents to prevent peptic ulcers or relieve dyspepsia was nearly twice as common in regular NSAID users (20-26%) than in non-NSAID users (11%). In Alberta, Canada, it has been estimated that NSAID use accounts for 28% of all prescriptions for anti-ulcer drugs in people aged at least 65 years. Many studies have now shown that NSAIDs increase the risk of peptic ulcer complications by 3-5-fold, and in several different populations it has been estimated that 15-35% of all peptic ulcer complications are due to NSAIDs. In the United States alone, there are an estimated 41,000 hospitalizations and 3,300 deaths each year among the elderly that are associated with NSAIDs. Factors that increase the risk of serious peptic ulcer disease include older age, history of peptic ulcer disease, gastrointestinal hemorrhage, dyspepsia, and/or previous NSAID intolerance, as well as several measures of poor health.",
"title": "Epidemiology of nonsteroidal anti-inflammatory drug-associated gastrointestinal injury."
},
{
"docid": "MED-5224",
"text": "Dry-eye syndrome (DES) is a multifactorial disease affecting millions of individuals worldwide. Various factors, including age, hormonal status, genetics, sex, immune status, innervation status, nutrition, pathogens, and environmental stress, can alter the cellular and molecular structure or function of components of the ocular surface system. The resulting imbalance increases susceptibility to desiccation and epithelial damage, leading to a vicious circle in which inflammation amplifies and sustains further damage by chronic deregulation of the system. Lubricating agents and steroids have been used as treatment options. However, as the causes of the disease become better elucidated, the more chemically complex cyclosporine A has become an increasingly useful treatment option and in the United States is currently the only Food and Drug Administration (FDA)-approved prescription drug for the treatment of dry eye. The safety and efficacy of cyclosporine have been shown in numerous studies.",
"title": "Safety and Efficacy of Cyclosporine in the Treatment of Chronic Dry Eye"
},
{
"docid": "MED-10",
"text": "Recent studies have suggested that statins, an established drug group in the prevention of cardiovascular mortality, could delay or prevent breast cancer recurrence but the effect on disease-specific mortality remains unclear. We evaluated risk of breast cancer death among statin users in a population-based cohort of breast cancer patients. The study cohort included all newly diagnosed breast cancer patients in Finland during 1995–2003 (31,236 cases), identified from the Finnish Cancer Registry. Information on statin use before and after the diagnosis was obtained from a national prescription database. We used the Cox proportional hazards regression method to estimate mortality among statin users with statin use as time-dependent variable. A total of 4,151 participants had used statins. During the median follow-up of 3.25 years after the diagnosis (range 0.08–9.0 years) 6,011 participants died, of which 3,619 (60.2%) was due to breast cancer. After adjustment for age, tumor characteristics, and treatment selection, both post-diagnostic and pre-diagnostic statin use were associated with lowered risk of breast cancer death (HR 0.46, 95% CI 0.38–0.55 and HR 0.54, 95% CI 0.44–0.67, respectively). The risk decrease by post-diagnostic statin use was likely affected by healthy adherer bias; that is, the greater likelihood of dying cancer patients to discontinue statin use as the association was not clearly dose-dependent and observed already at low-dose/short-term use. The dose- and time-dependence of the survival benefit among pre-diagnostic statin users suggests a possible causal effect that should be evaluated further in a clinical trial testing statins’ effect on survival in breast cancer patients.",
"title": "Statin Use and Breast Cancer Survival: A Nationwide Cohort Study from Finland"
},
{
"docid": "MED-1348",
"text": "Background Meta-analyses of antidepressant medications have reported only modest benefits over placebo treatment, and when unpublished trial data are included, the benefit falls below accepted criteria for clinical significance. Yet, the efficacy of the antidepressants may also depend on the severity of initial depression scores. The purpose of this analysis is to establish the relation of baseline severity and antidepressant efficacy using a relevant dataset of published and unpublished clinical trials. Methods and Findings We obtained data on all clinical trials submitted to the US Food and Drug Administration (FDA) for the licensing of the four new-generation antidepressants for which full datasets were available. We then used meta-analytic techniques to assess linear and quadratic effects of initial severity on improvement scores for drug and placebo groups and on drug–placebo difference scores. Drug–placebo differences increased as a function of initial severity, rising from virtually no difference at moderate levels of initial depression to a relatively small difference for patients with very severe depression, reaching conventional criteria for clinical significance only for patients at the upper end of the very severely depressed category. Meta-regression analyses indicated that the relation of baseline severity and improvement was curvilinear in drug groups and showed a strong, negative linear component in placebo groups. Conclusions Drug–placebo differences in antidepressant efficacy increase as a function of baseline severity, but are relatively small even for severely depressed patients. The relationship between initial severity and antidepressant efficacy is attributable to decreased responsiveness to placebo among very severely depressed patients, rather than to increased responsiveness to medication. Editors' Summary Background. Everyone feels miserable occasionally. But for some people—those with depression—these sad feelings last for months or years and interfere with daily life. Depression is a serious medical illness caused by imbalances in the brain chemicals that regulate mood. It affects one in six people at some time during their life, making them feel hopeless, worthless, unmotivated, even suicidal. Doctors measure the severity of depression using the “Hamilton Rating Scale of Depression” (HRSD), a 17–21 item questionnaire. The answers to each question are given a score and a total score for the questionnaire of more than 18 indicates severe depression. Mild depression is often treated with psychotherapy or talk therapy (for example, cognitive–behavioral therapy helps people to change negative ways of thinking and behaving). For more severe depression, current treatment is usually a combination of psychotherapy and an antidepressant drug, which is hypothesized to normalize the brain chemicals that affect mood. Antidepressants include “tricyclics,” “monoamine oxidases,” and “selective serotonin reuptake inhibitors” (SSRIs). SSRIs are the newest antidepressants and include fluoxetine, venlafaxine, nefazodone, and paroxetine. Why Was This Study Done? Although the US Food and Drug Administration (FDA), the UK National Institute for Health and Clinical Excellence (NICE), and other licensing authorities have approved SSRIs for the treatment of depression, some doubts remain about their clinical efficacy. Before an antidepressant is approved for use in patients, it must undergo clinical trials that compare its ability to improve the HRSD scores of patients with that of a placebo, a dummy tablet that contains no drug. Each individual trial provides some information about the new drug's effectiveness but additional information can be gained by combining the results of all the trials in a “meta-analysis,” a statistical method for combining the results of many studies. A previously published meta-analysis of the published and unpublished trials on SSRIs submitted to the FDA during licensing has indicated that these drugs have only a marginal clinical benefit. On average, the SSRIs improved the HRSD score of patients by 1.8 points more than the placebo, whereas NICE has defined a significant clinical benefit for antidepressants as a drug–placebo difference in the improvement of the HRSD score of 3 points. However, average improvement scores may obscure beneficial effects between different groups of patient, so in the meta-analysis in this paper, the researchers investigated whether the baseline severity of depression affects antidepressant efficacy. What Did the Researchers Do and Find? The researchers obtained data on all the clinical trials submitted to the FDA for the licensing of fluoxetine, venlafaxine, nefazodone, and paroxetine. They then used meta-analytic techniques to investigate whether the initial severity of depression affected the HRSD improvement scores for the drug and placebo groups in these trials. They confirmed first that the overall effect of these new generation of antidepressants was below the recommended criteria for clinical significance. Then they showed that there was virtually no difference in the improvement scores for drug and placebo in patients with moderate depression and only a small and clinically insignificant difference among patients with very severe depression. The difference in improvement between the antidepressant and placebo reached clinical significance, however, in patients with initial HRSD scores of more than 28—that is, in the most severely depressed patients. Additional analyses indicated that the apparent clinical effectiveness of the antidepressants among these most severely depressed patients reflected a decreased responsiveness to placebo rather than an increased responsiveness to antidepressants. What Do These Findings Mean? These findings suggest that, compared with placebo, the new-generation antidepressants do not produce clinically significant improvements in depression in patients who initially have moderate or even very severe depression, but show significant effects only in the most severely depressed patients. The findings also show that the effect for these patients seems to be due to decreased responsiveness to placebo, rather than increased responsiveness to medication. Given these results, the researchers conclude that there is little reason to prescribe new-generation antidepressant medications to any but the most severely depressed patients unless alternative treatments have been ineffective. In addition, the finding that extremely depressed patients are less responsive to placebo than less severely depressed patients but have similar responses to antidepressants is a potentially important insight into how patients with depression respond to antidepressants and placebos that should be investigated further. Additional Information. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050045.",
"title": "Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration"
},
{
"docid": "MED-2284",
"text": "In 1999, drug manufacturers introduced a class of NSAIDs called COX-2 inhibitors or coxibs. The drugs were avidly promoted directly to the consumers and became bestsellers from the start. Arthritis sufferers were eager to take medications that eased joint pain with less risk of causing gastrointestinal pain, bleeding and other side-effects. In the year after their introduction, doctors wrote over 100 million prescriptions for celecoxib (Celebrex) and rofecoxib (Vioxx). Celebrex is the sixth best-selling drug, with sales of more than US$ 4 billion since its debut in 1999. Vioxx had sales of US$ 2.6 billion in 2001. However, the coxibs increase the risk of heart attacks and strokes, and their price, in the USA, is obscene. The manufacturers faced a possibly complicit, toothless and bloodless FDA, and used every maneuvering to fleece the patients. We must now reflect on attitudes that we thought only belong to the tobacco industry. Fortunately, safe and active alternatives exist.",
"title": "COX-2 inhibitors: a story of greed, deception and death."
},
{
"docid": "MED-2759",
"text": "A commercial weight loss program with a client base composed of >95% women experienced sporadic complaints of nausea and vomiting after changing its multivitamin supplier. This retrospective and observational study was designed to determine if related adverse event reports were significant, and to investigate potential mechanism for their occurrence in this group of subjects, many of whom were concurrently receiving oral contraceptives or hormone replacement therapy. Incidence of nausea, vomiting, rash, and total complaints in the 3 months following the change of the multivitamin formulation was compared with the same complaints in the 3 months before the change. In the 3 months following the multivitamin change, there were 166 complaints of nausea and vomiting, 9 complaints of rash and 194 total complaints from a group of 88,468 patients. In the 3 months before the change in the multivitamin, there had been 2 complaints of nausea and vomiting, no complaints of rash, and 11 total complaints from 88,252 patients. The difference detected by a chi-squared test was significant for all events studied; nausea and vomiting (P < 0.0001), rash (P < 0.02), and total complaints (P < 0.0001). The altered multivitamins contained added citrus bioflavanoids not included in the original formula. Citrus bioflavanoids decrease the clearance of exogenous estrogens by inhibiting cytochrome P450 enzyme systems. Elevated estrogen levels could account for the increased incidence of nausea and vomiting. This experience demonstrates that adding dietary herbal supplements to multivitamins may be associated with adverse interactions with prescription drugs.",
"title": "Vomiting from multivitamins: a potential drug interaction."
},
{
"docid": "MED-4365",
"text": "A myriad of health claims are being made in favor of the consumption of green tea. However, mostly due to the easy availability and greater than ever popularity of highly concentrated green tea extracts, sometimes combined with an attitude of more-is-better, certain health risks of green tea consumption have begun to emerge. Among such risks are the possibility of liver damage, the potential to interact with prescription drugs to alter their therapeutic efficacy, and the chance to cause harm when combined with other highly popular herbal remedies. This review will summarize documented examples of adverse effects of green tea in humans, and will discuss risks of copious consumption of highly concentrated green tea extracts as indicated by studies in animals. While there is no intention to minimize any of the scientifically established benefits of the use of green tea, the purpose of this review is to focus primarily on the potential for adverse effects and raise awareness of the rare, yet under-appreciated risks. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",
"title": "Adverse effects of concentrated green tea extracts."
},
{
"docid": "MED-2808",
"text": "Chemotherapy remains the core of anticancer treatment. However, despite the tremendous strides made in the development of targeted anticancer therapies, emergence of resistance to chemotherapeutic drugs is still a major obstacle in the successful management of resistant tumours. Therefore, profound investigation into the in-depth molecular mechanisms of drug resistance is essential and may hopefully translate into effective therapies that can flip the switch from drug resistance to susceptibility. Mechanistically, resistance phenomena may be explained by (i) overexpression of drug efflux pumps, (ii) enhanced drug detoxification, (iii) rapid DNA repair efficiency, (iv) defects in apoptosis regulation, and (v) active cell survival signals. Several adverse effects associated with multidrug resistance and the need for safe multi-targeted anticancer drugs instigated the use of the phytochemical, curcumin, the yellow pigment of the spice turmeric, which has pleotropic activities. We performed a structured literature review using PubMed and Medline searches with secondary review of cited publications, identifying studies on the role of curcumin in conquering drug resistance in cancer. This review describes how curcumin sensitizes cancer cells through regulation of multiple multidrug resistance pathways, thus employing one drug for multiple targets. Curcumin helps the cancer cells to regain their 'forgotten' apoptosis, modulates drug-target interaction at different levels, restrains survival pathways when their proteins are overexpressed, and finds an alternate way to carry forward the process of sensitization of different resistant tumours. Additionally, the review dissects the role of curcumin, if any, in targeting the major culprit of drug resistance, cancer stem cells (CSC), thereby circumventing resistance. Taken together, this review strongly suggests that curcumin is a promising chemosensitizing agent and that the unique properties of curcumin may be exploited for successful management of resistant tumours.",
"title": "Death by design: where curcumin sensitizes drug-resistant tumours."
},
{
"docid": "MED-2083",
"text": "Coronary artery disease is responsible for much mortality and morbidity around the world. Platelets are involved in atherosclerotic disease development and the reduction of platelet activity by medications reduces the incidence and severity of disease. Red wine and grapes contain polyphenolic compounds, including flavonoids, which can reduce platelet aggregation and have been associated with lower rates of cardiovascular disease. Citrus fruits contain different classes of polyphenolics that may not share the same properties. This study evaluated whether commercial grape, orange and grapefruit juices, taken daily, reduce ex vivo platelet activity. In a randomized cross-over design, ten healthy human subjects (ages 26-58 y, five of each gender) drank 5-7.5 mL/(kg. d) of purple grape juice, orange juice or grapefruit juice for 7-10 d each. Platelet aggregation (whole blood impedance aggregometry, Chronolog Model #590) at baseline was compared to results after consumption of each juice. Drinking purple grape juice for one week reduced the whole blood platelet aggregation response to 1 mg/L of collagen by 77% (from 17.9 +/- 2.3 to 4.0 +/- 6.8 ohms, P = 0.0002). Orange juice and grapefruit juice had no effect on platelet aggregation. The purple grape juice had approximately three times the total polyphenolic concentration of the citrus juices and was a potent platelet inhibitor in healthy subjects while the citrus juices showed no effect. The platelet inhibitory effect of the flavonoids in grape juice may decrease the risk of coronary thrombosis and myocardial infarction.",
"title": "Grape juice, but not orange juice or grapefruit juice, inhibits human platelet aggregation."
},
{
"docid": "MED-2105",
"text": "DNA damage is an essential component of the genesis of colonic cancer. Gut microbial products and food components are thought to be principally responsible for the damage that initiates disease progression. Modified Ames tests and Comet assays have been developed for measuring mutagenicity and genotoxicity. Their relevance to oncogenesis remains to be confirmed, as does the relative importance of different mutagenic and genotoxic compounds present in fecal water and the bacteria involved in their metabolism. Dietary intervention studies provide clues to the likely risks of oncogenesis. High-protein diets lead to increases in N-nitroso compounds in fecal water and greater DNA damage as measured by the Comet assay, for example. Other dietary interventions, such as non-digestible carbohydrates and probiotics, may lead to lower fecal genotoxicity. In order to make recommendations to the general public, we must develop a better understanding of how genotoxic compounds are formed in the colon, how accurate the Ames and Comet assays are, and how diet affects genotoxicity.",
"title": "Recent Perspectives on the Relations between Fecal Mutagenicity, Genotoxicity, and Diet"
},
{
"docid": "MED-2335",
"text": "Xenohormesis is a biological principle that explains how environmentally stressed plants produce bioactive compounds that can confer stress resistance and survival benefits to animals that consume them. Animals can piggyback off products of plants' sophisticated stress response which has evolved as a result of their stationary lifestyle. Factors eliciting the plant stress response can judiciously be employed to maximize yield of health-promoting plant compounds. The xenohormetic plant compounds can, when ingested, improve longevity and fitness by activating the animal's cellular stress response and can be applied in drug discovery, drug production, and nutritional enhancement of diet.",
"title": "Xenohormesis: health benefits from an eon of plant stress response evolution"
},
{
"docid": "MED-3744",
"text": "Consumption of fruits and vegetables has been associated with reduced risk of chronic diseases such as cardiovascular disease and cancer. Phytochemicals, especially phenolics, in fruits and vegetables are suggested to be the major bioactive compounds for the health benefits. However, the phenolic contents and their antioxidant activities in fruits and vegetables were underestimated in the literature, because bound phenolics were not included. This study was designed to investigate the profiles of total phenolics, including both soluble free and bound forms in common fruits, by applying solvent extraction, base digestion, and solid-phase extraction methods. Cranberry had the highest total phenolic content, followed by apple, red grape, strawberry, pineapple, banana, peach, lemon, orange, pear, and grapefruit. Total antioxidant activity was measured using the TOSC assay. Cranberry had the highest total antioxidant activity (177.0 +/- 4.3 micromol of vitamin C equiv/g of fruit), followed by apple, red grape, strawberry, peach, lemon, pear, banana, orange, grapefruit, and pineapple. Antiproliferation activities were also studied in vitro using HepG(2) human liver-cancer cells, and cranberry showed the highest inhibitory effect with an EC(50) of 14.5 +/- 0.5 mg/mL, followed by lemon, apple, strawberry, red grape, banana, grapefruit, and peach. A bioactivity index (BI) for dietary cancer prevention is proposed to provide a new alternative biomarker for future epidemiological studies in dietary cancer prevention and health promotion.",
"title": "Antioxidant and antiproliferative activities of common fruits."
},
{
"docid": "MED-3974",
"text": "BACKGROUND: Viral respiratory tract infection (VRTI) is the most common illness in humans. Despite the high incidence, the economic impact of non-influenza-related VRTI has not been rigorously explored. Our objectives were to obtain an updated incidence of non-influenza-related VRTI in the United States and to quantify the health care resource use (direct costs) and productivity losses (indirect costs) associated with these infections. METHODS: A nationwide telephone survey of US households (N = 4051) was conducted between November 3, 2000, and February 12, 2001 to obtain a representative estimate of the self-reported incidence of non-influenza-related VRTI and related treatment patterns. Direct treatment costs measured included outpatient clinician encounters, use of over-the-counter and prescription drugs, and associated infectious complications of non-influenza-related VRTI. Absenteeism estimates for infected individuals and parents of infected children were extrapolated from National Health Interview Survey data. RESULTS: Of survey respondents, 72% reported a non-influenza-related VRTI within the past year. Respondents who experienced a self-reported non-influenza-related VRTI averaged 2.5 episodes annually. When these rates are extrapolated to the entire US population, approximately 500 million non-influenza-related VRTI episodes occur per year. Similarly, if the treatment patterns reported by the respondents are extended to the population, the total economic impact of non-influenza-related VRTI approaches $40 billion annually (direct costs, $17 billion per year; and indirect costs, $22.5 billion per year). CONCLUSIONS: Largely because of the high attack rate, non-influenza-related VRTI imposes a greater economic burden than many other clinical conditions. The pending availability of effective antiviral therapies warrants increased attention be paid to this common and expensive illness.",
"title": "The economic burden of non-influenza-related viral respiratory tract infection in the United States."
},
{
"docid": "MED-1716",
"text": "Obesity has reached epidemic proportions in the developed world. The progression from obesity to diabetes mellitus type 2, via metabolic syndrome, is recognised, and the significant associated increase in the risk of major human cancers acknowledged. We review the molecular basis of the involvement of morbidly high concentrations of endogenous or therapeutic insulin and of insulin-like growth factors in the progression from obesity to diabetes and finally to cancer. Epidemiological and biochemical studies establish the role of insulin and hyperinsulinaemia in cancer risk and progression. Insulin-like growth factors, IGF-1 and IGF-2, secreted by visceral or mammary adipose tissue have significant paracrine and endocrine effects. These effects can be exacerbated by increased steroid hormone production. Structural studies elucidate how each of the three ligands, insulin, IGF-1, and IGF-2, interacts differently with isoforms A and B of the insulin receptor and with type I IGF receptor and explain how these protagonists contribute to diabetes-associated cancer. The above should inform appropriate treatment of cancers that arise in obese individuals and in those with diabetes mellitus type 2. Novel drugs that target the insulin and insulin-like growth factor signal transduction pathways are in clinical trial and should be effective if appropriate biomarker-informed patient stratification is implemented.",
"title": "A Twenty-First Century Cancer Epidemic Caused by Obesity: The Involvement of Insulin, Diabetes, and Insulin-Like Growth Factors"
},
{
"docid": "MED-2266",
"text": "BACKGROUND: Exposure to over-the-counter (OTC) ibuprofen and other OTC non-steroidal anti-inflammatory drugs (NSAIDs) is substantial. Although the literature on gastrointestinal (GI) safety of NSAID therapy is extensive, the risk profiles of OTC and prescription dosing are seldom separated, and few studies provide risks specific to OTC ibuprofen. OBJECTIVE: To conduct a literature review to evaluate the risk of GI bleeding events related to OTC ibuprofen use. METHODS: Published clinical trials, observational studies, and meta-analyses of OTC ibuprofen use, defined as up to 1200 mg/day or stated as 'over the counter,' reporting endpoints of incidence rates and proportions of GI bleeding events (e.g., GI bleeding-related hospitalizations and deaths) were identified via MEDLINE through 2010. Data from these studies were summarized. RESULTS: Twenty studies (nine observational, ten clinical trials, one meta-analysis) reporting incidence rates and proportions of a GI bleeding-related event associated with OTC or OTC-specific doses of ibuprofen were included. The frequency of a GI-related hospitalization was <0.2% for patients on OTC-comparable doses. Incidence rates among those using OTC-comparable doses ranged from 0 to 3.19 per 1000 patient-years. The incidence of a GI bleeding-related event increased with age and the use of concomitant medications, and there was a general, though not always statistically significant, ibuprofen dose-response relationship. The relative risk of any GI bleeding-related event ranged from 1.1 to 2.4 for users of OTC-specific doses of ibuprofen compared to non-users. CONCLUSIONS: Studies reported low incidence of GI bleeding events with use of OTC ibuprofen. Few published studies that specifically investigated OTC ibuprofen use were identified. Varying methodologies and definitions of exposure and outcomes prevented direct comparison of many results. Only studies that used the methods herein described were identified. Further research evaluating the risk of GI bleeding events in patients taking OTC-specific ibuprofen use may be useful.",
"title": "Over-the-counter ibuprofen and risk of gastrointestinal bleeding complications: a systematic literature review."
},
{
"docid": "MED-2182",
"text": "Over the past century, a major shift in North American food practices has been taking place. However, the literature on this topic is lacking in several areas. Some available research on food and cooking practices in the current context is presented, with a focus on how these are affecting health and how they might be contributing to health inequalities within the population. First, cooking and cooking skills are examined, along with the ambiguities related to terms associated with cooking in the research literature. Food choice, cooking, and health are described, particularly in relation to economic factors that may lead to health inequalities within the population. The importance of developing an understanding of factors within the wider food system as part of food choice and cooking skills is presented, and gaps in the research literature are examined and areas for future research are presented. Cooking practices are not well studied but are important to an understanding of human nutritional health as it relates to cultural, environmental, and economic factors.",
"title": "Food, cooking skills, and health: a literature review."
},
{
"docid": "MED-1490",
"text": "OBJECTIVES: The study aimed to find the threshold of benefit for a hypothetical cholesterol-lowering drug below which the subject would not be prepared to take the drug. We also looked at whether proximity to the target event (myocardial infarction) and the subjects' views on drug taking affected this threshold. DESIGN: We studied 307 subjects using a written questionnaire and interview. Group 1 (102 subjects) had just been discharged from the coronary care unit. Group 2 (105 subjects) were taking cardio-protective drugs but had no recent history of myocardial infarction. Group 3 (100 subjects) had no history of myocardial infarction and were taking no cardio-protective drugs. RESULTS: Median values for the threshold of benefit below which the subject would not take the preventive drug were 20%, 20%, and 30% absolute risk reduction for Groups 1, 2 and 3 respectively. Median values for expectation of average prolongation of life were 12, 12 and 18 months respectively. Only 27% of subjects would take a drug offering 5% or less absolute risk reduction over five years. Subjects' views on medicinal drug taking in general and proximity to the target event were predictors of the acceptance of preventive drugs. Eighty percent of subjects wished to be told the numerical benefit of a preventive drug before starting on it. CONCLUSION: For the majority, the expectation of benefit from a preventive drug is higher than the actual benefit provided by current drug strategies. There is a tension between the patient's right to know about the chance of benefiting from a preventive drug and the likely reduction in uptake if they are so informed.",
"title": "Are preventive drugs preventive enough? A study of patients' expectation of benefit from preventive drugs."
},
{
"docid": "MED-1343",
"text": "BACKGROUND: Evidence-based medicine is valuable to the extent that the evidence base is complete and unbiased. Selective publication of clinical trials--and the outcomes within those trials--can lead to unrealistic estimates of drug effectiveness and alter the apparent risk-benefit ratio. METHODS: We obtained reviews from the Food and Drug Administration (FDA) for studies of 12 antidepressant agents involving 12,564 patients. We conducted a systematic literature search to identify matching publications. For trials that were reported in the literature, we compared the published outcomes with the FDA outcomes. We also compared the effect size derived from the published reports with the effect size derived from the entire FDA data set. RESULTS: Among 74 FDA-registered studies, 31%, accounting for 3449 study participants, were not published. Whether and how the studies were published were associated with the study outcome. A total of 37 studies viewed by the FDA as having positive results were published; 1 study viewed as positive was not published. Studies viewed by the FDA as having negative or questionable results were, with 3 exceptions, either not published (22 studies) or published in a way that, in our opinion, conveyed a positive outcome (11 studies). According to the published literature, it appeared that 94% of the trials conducted were positive. By contrast, the FDA analysis showed that 51% were positive. Separate meta-analyses of the FDA and journal data sets showed that the increase in effect size ranged from 11 to 69% for individual drugs and was 32% overall. CONCLUSIONS: We cannot determine whether the bias observed resulted from a failure to submit manuscripts on the part of authors and sponsors, from decisions by journal editors and reviewers not to publish, or both. Selective reporting of clinical trial results may have adverse consequences for researchers, study participants, health care professionals, and patients. Copyright 2008 Massachusetts Medical Society.",
"title": "Selective publication of antidepressant trials and its influence on apparent efficacy."
},
{
"docid": "MED-4371",
"text": "OBJECTIVES: To ascertain the recommendations, training and education of health food store employees and determine how they communicate the costs, benefits and risks associated with natural health products for the HIV/AIDS community. METHODS: Four male research assistants, posing as asymptomatic HIV-positive individuals, inquired of employees of all retail health food stores in a major Canadian city as to what is recommended for their condition. The research assistants asked about product costs, side effects, potential drug interactions and efficacy. They also inquired as to employee education related to Complementary and Alternative Medicine (CAM) and noted whether employees asked about which conventional medications they were taking and whether they recommended that the subjects seek physician or CAM provider advice. RESULTS: A total of 32 stores were included. Eight store employees (25%) offered no advice; eight (25%) inquired whether the subjects were currently taking medications; six (19%) suggested visiting a physician; and eight (25%) suggested visiting a CAM provider. A total of 36 different products (mean 2.3 per employee) were recommended with considerable variability in product evidence and cost. The education of the employees varied from postgraduate education (n=3), to undergraduate degree (n=3), college level (n=5) in CAM, or no formal education in CAM (n=21). CONCLUSION: There was considerable heterogeneity in advice on natural food products provided by employees of natural food stores and, in general, these individuals had limited formal training in CAM. The products they recommended had limited evidence supporting their efficacy and in some instances were potentially harmful and had considerable costs. The findings of this study support the need to further examine how best to regulate this growing component of the health care system.",
"title": "Emerging issues associated with HIV patients seeking advice from health food stores."
},
{
"docid": "MED-2315",
"text": "Background The word selectivity describes a drug's ability to affect a particular cell population in preference to others. As part of the current state of art in the search for new therapeutic agents, the property of selectivity is a mode of action thought to have a high degree of desirability. Consequently there is a growing activity in this area of research. Selectivity is generally a worthy property in a drug because a drug having high selectivity may have a dramatic effect when there is a single agent that can be targeted against the appropriate molecular-driver involved in the pathogenesis of a disease. An example is chronic myeloid leukemia (CML). CML has a specific chromosomal abnormality, the Philadelphia chromosome, that results in a single gene that produces an abnormal protein Discussion There is a burgeoning understanding of the cellular mechanisms that control the etiology and pathogeneses of diseases. This understanding both enables and motivates the development of drugs that induce a specific action in a selected cell population; i.e., a targeted treatment. Consequently, drugs that can target distinct molecular targets involved in pathologic/pathogenetic processes, or signal-transduction pathways, are being developed. However, in most cases, diseases involve multiple abnormalities. A disease may be associated with more than one dysfunctional protein and these may be out-of-balance with each other. Likewise a drug might strongly target a protein that shares a similar active domain with other proteins. A drug may also target pleiotropic cytokines, or other proteins that have multi-physiological functions. In this way multiple normal cellular pathways can be simultaneously influenced. Long term experience with drugs supposedly designed for only a single target, but which unavoidably involve other functional effects, is uncovering the fact that molecular targeting is not medically flawless. Summary We contend that an ideal drug may be one whose efficacy is based not on the inhibition of a single target, but rather on the rebalancing of the several proteins or events, that contribute to the etiology, pathogeneses, and progression of diseases, i.e., in effect a promiscuous drug. Ideally, if this could be done at minimum drug concentration, side effects could be minimized. Corollaries to this argument are that the growing fervor for researching truly selective drugs may be imprudent when considering the totality of responses; and that the expensive screening techniques used to discover these, may be both medically and financially inefficient.",
"title": "Promiscuous drugs compared to selective drugs (promiscuity can be a virtue)"
},
{
"docid": "MED-2132",
"text": "The mammalian target of rapamycin (mTOR) is a protein kinase that plays key roles in cellular regulation. It forms complexes with additional proteins. The best-understood one is mTOR complex 1 (mTORC1). The regulation and cellular functions of mTORC1 have been the subjects of intense study; despite this, many questions remain to be answered. They include questions about the actual mechanisms by which mTORC1 signaling is stimulated by hormones and growth factors, which involves the small GTPase Rheb, and by amino acids, which involves other GTPase proteins. The control of Rheb and the mechanism by which it activates mTORC1 remain incompletely understood. Although it has been known for many years that rapamycin interferes with some functions of mTORC1, it is not known how it does this, or why only some functions of mTORC1 are affected. mTORC1 regulates diverse cellular functions. Several mTORC1 substrates are now known, although in several cases their physiological roles are poorly or incompletely understood. In the case of several processes, although it is clear that they are regulated by mTORC1, it is not known how mTORC1 does this. Lastly, mTORC1 is implicated in ageing, but again it is unclear what mechanisms account for this. Given the importance of mTORC1 signaling both for cellular functions and in human disease, it is a high priority to gain further insights into the control of mTORC1 signaling and the mechanisms by which it controls cellular functions and animal physiology.",
"title": "mTORC1 signaling: what we still don't know."
},
{
"docid": "MED-2112",
"text": "Medical students in the United States are taught little about nutrition and dietetics. Worse yet, their training biases them against the studies that show the power of dietary approaches to managing disease. The current approach to evidence-based medicine encourages physicians to ignore any information that does not come from a double-blind, randomized controlled trial. Yet human beings cannot be blinded to a dietary intervention. As a result, physicians are biased toward drug treatments and against dietary interventions for the management of chronic disease. Copyright © 2013 Elsevier Ltd. All rights reserved.",
"title": "How evidence-based medicine biases physicians against nutrition."
},
{
"docid": "MED-2004",
"text": "The incidence and prevalence of diabetes (primarily type 2 diabetes) has risen sharply since 1990. It is projected to increase another 64% between 2010 and 2025, affecting 53.1 million people and resulting in medical and societal costs of a half trillion dollars a year. We know how to prevent many cases of diabetes and how to treat it effectively. Early appropriate treatment makes a significant difference in preventing major complications and reducing premature death, but it does not cure the disease. Early detection of prediabetes, in conjunction with lifestyle changes, can reduce the number of people with diabetes. A dramatic reduction in diabetes prevalence over time will require significant lifestyle changes on the part of society as a whole. The purpose of this study is to increase public awareness of the severity of regional diabetes trends by providing detailed forecasts for all states and several metropolitan areas for 2010, 2015, and 2025. A model was created to utilize the latest national diabetes and population data and projections, and to transform these into state and metropolitan area forecasts for the whole population and major subgroups. These forecasts were then summarized in easy-to-understand briefing papers for each state and selected metro areas, which are provided online for easy public access. This research is important because little data exist that project the future prevalence and potential costs of diabetes at the state and metro area level. With this data, key stakeholders can make informed decisions concerning diabetes, its impact on their communities, and resource allocation.",
"title": "Creating public awareness: state 2025 diabetes forecasts."
},
{
"docid": "MED-1240",
"text": "New antiemetic drug developments, formulations, guidelines, risk evaluation, and controversies have occurred in the area of postoperative nausea and vomiting (PONV). These developments have helped improve our understanding of the prevention and treatment of PONV in the postanesthesia care unit and after discharge home or to the hospital ward. Antiemetic drug research has resulted in the introduction of the second-generation 5-hydroxytryptamine-3 (5-HT3) receptor antagonist palonosetron and the neurokinin-1 (NK-1) receptor antagonist aprepitant, as well as new data on existing antiemetics. The next frontier and need for further nausea and vomiting research and therapy is the area of postdischarge nausea and vomiting after the patient is discharged home from phase II of the ambulatory stepdown unit or to the hospital ward. Antiemetic drug selection depends on efficacy, cost, safety, and ease of dosing. Safety concerns have arisen regarding the side effects of antiemetics, specifically their effect on the ECG with prolongation of the QTc interval by the butyrophenones and the first-generation 5-HT3 receptor antagonist class of antiemetics. The impact of pharmocogenetics on antiemetic drug metabolism and their resulting efficacy has been correlated with genetic makeup affecting drug response. A discussion of ethics in PONV research has been initiated by the meta-analysis of PONV studies. To help guide antiemetic selection and PONV therapy for clinical practitioners, the Society of Ambulatory Anesthesia (SAMBA) PONV consensus guidelines have been introduced and updated.",
"title": "Update on the management of postoperative nausea and vomiting."
},
{
"docid": "MED-5032",
"text": "The relation between the intake of certain food items thought to be precursors or inhibitors of N-nitroso compounds (NOC) and risk of leukemia was investigated in a case-control study among children from birth to age 10 years in Los Angeles County, California (United States). Cases were ascertained through a population-based tumor registry from 1980 to 1987. Controls were drawn from friends and by random-digit dialing. Interviews were obtained from 232 cases and 232 controls. Food items of principal interest were: breakfast meats (bacon, sausage, ham); luncheon meats (salami, pastrami, lunch meat, corned beef, bologna); hot dogs; oranges and orange juice; and grapefruit and grapefruit juice. We also asked about intake of apples and apple juice, regular and charcoal broiled meats, milk, coffee, and coke or cola drinks. Usual consumption frequencies were determined for both parents and the child. When the risks were adjusted for each other and other risk factors, the only persistent significant associations were for children's intake of hot dogs (odds ratio [OR] = 9.5, 95 percent confidence interval [CI] = 1.6-57.6 for 12 or more hot dogs per month, trend P = 0.01), and fathers' intake of hot dogs (OR = 11.0, CI = 1.2-98.7 for highest intake category, trend P = 0.01). There was no evidence that fruit intake provided protection. While these results are compatible with the experimental animal literature and the hypothesis that human NOC intake is associated with leukemia risk, given potential biases in the data, further study of this hypothesis with more focused and comprehensive epidemiologic studies is warranted.",
"title": "Processed meats and risk of childhood leukemia (California, USA)."
},
{
"docid": "MED-2161",
"text": "BACKGROUND & AIMS: Coffee consumption has been suggested to reduce the risk for hepatocellular carcinoma (HCC). We performed a meta-analysis of epidemiological studies to provide updated information on how coffee drinking affects HCC risk. METHODS: We performed a PubMed/MEDLINE search of the original articles published in English from 1966 through September 2012, on case-control or cohort studies that associated coffee consumption with liver cancer or HCC. We calculated the summary relative risk (RR) for any, low, and high consumption of coffee vs no consumption. The cut-off point for low vs high consumption was set to 3 cups per day in 9 studies and 1 cup per day in 5 studies. RESULTS: The summary RR for any coffee consumption vs no consumption was 0.60 from 16 studies, comprising a total of 3153 HCC cases (95% confidence interval [CI], 0.50-0.71); the RRs were 0.56 from 8 case-control studies (95% CI, 0.42-0.75) and 0.64 from 8 cohort studies (95% CI, 0.52-0.78). Compared with no coffee consumption, the summary RR was 0.72 (95% CI, 0.61-0.84) for low consumption and 0.44 (95% CI, 0.39-0.50) for high consumption. The summary RR was 0.80 (95% CI, 0.77-0.84) for an increment of 1 cup of coffee per day. The inverse relationship between coffee and HCC risk was consistent regardless of the subjects' sex, alcohol drinking, or history of hepatitis or liver disease. CONCLUSIONS: From this meta-analysis, the risk of HCC is reduced by 40% for any coffee consumption vs no consumption. The inverse association might partly or largely exist because patients with liver and digestive diseases reduce their coffee intake. However, coffee has been shown to affect liver enzymes and development of cirrhosis, and therefore could protect against liver carcinogenesis. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.",
"title": "Coffee reduces risk for hepatocellular carcinoma: an updated meta-analysis."
},
{
"docid": "MED-3056",
"text": "Opioids are important in reward processes leading to addictive behavior such as self-administration of opioids and other drugs of abuse including nicotine and alcohol. Opioids are also involved in a broadly distributed neural network that regulates eating behavior, affecting both homeostatic and hedonic mechanisms. In this sense, opioids are particularly implicated in the modulation of highly palatable foods, and opioid antagonists attenuate both addictive drug taking and appetite for palatable food. Thus, craving for palatable food could be considered as a form of opioid-related addiction. There are three main families of opioid receptors (µ, ĸ, and δ) of which µ-receptors are most strongly implicated in reward. Administration of selective µ-agonists into the NAcc of rodents induces feeding even in satiated animals, while administration of µ-antagonists reduces food intake. Pharmacological studies also suggest a role for ĸ- and δ-opioid receptors. Preliminary data from transgenic knockout models suggest that mice lacking some of these receptors are resistant to high-fat diet-induced obesity. Copyright © 2012 S. Karger GmbH, Freiburg.",
"title": "The opioid system and food intake: homeostatic and hedonic mechanisms."
},
{
"docid": "MED-4536",
"text": "The cytotoxic effects of aqueous extract of Triphala, an ayurvedic formulation, were investigated on human breast cancer cell line (MCF-7) and a transplantable mouse thymic lymphoma (barcl-95). The viability of treated cells was found to decrease with the increasing concentrations of Triphala. On the other hand, treatment of normal breast epithelial cells, MCF-10 F, human peripheral blood mononuclear cells, mouse liver and spleen cells, with similar concentrations of Triphala did not affect their cytotoxicity significantly. The drug treatment was found to induce apoptosis in MCF-7 and barcl-95 cells in vitro as determined by annexin-V fluorescence and proportion of apoptotic cells was found dependent on Triphala concentration. MCF-7 cells treated with Triphala when subjected to single cell gel electrophoresis, revealed a pattern of DNA damage, characteristic of apoptosis. Studies on Triphala treated MCF-7 and barcl-95 cells showed significant increase in intracellular reactive oxygen species (ROS) in a concentration dependent manner. ROS increase was, however, found to be insignificant in MCF-10 F as well as in murine spleen and liver normal cells. In vivo, direct oral feeding of Triphala to mice (40 mg/kg body weight) transplanted with barcl-95 produced significant reduction in tumor growth as evaluated by tumor volume measurement. It was also found that apoptosis was significantly higher in the excised tumor tissue of Triphala fed mice as compared to the control, suggesting the involvement of apoptosis in tumor growth reduction. These results suggest that Triphala possessed ability to induce cytotoxicity in tumor cells but spared the normal cells. The differential effect of Triphala on normal and tumor cells seems to be related to its ability to evoke differential response in intracellular ROS generation. The differential response of normal and tumor cells to Triphala in vitro and the substantial regression of transplanted tumor in mice fed with Triphala points to its potential use as an anticancer drug for clinical treatment.",
"title": "Potential of traditional ayurvedic formulation, Triphala, as a novel anticancer drug."
}
] |
4091
|
How do you find reasonably priced, quality, long lasting clothing?
|
[
{
"docid": "82209",
"text": "According to this http://shine.yahoo.com/event/financiallyfit/cheapest-days-to-shop-online-2301854/ Tuesday is the best day of the week to buy men's apparel.",
"title": ""
},
{
"docid": "86280",
"text": "Are specific brand recommendations allowed? I'm a big fan of Lands' End. They have good quality clothing at reasonable prices in all the basic styles. They have great customer service and you con order online and avoid clothes shopping at the mall (which I hate).",
"title": ""
},
{
"docid": "447123",
"text": "Use resources like Consumer Reports and recommendations from like-minded friends to figure out brands which have a reputation for making quality clothes. Then trust, but verify. Ideally have a friend who sews a lot go with you on a clothing expedition if you don't know how to determine quality in clothing. People who sew knew their fabrics, and this could be very helpful to you. Start at places that are known for quality clothing, but make sure the reputation hasn't outlived reality. I'd look for: Once you've identified places that you can trust, wait for sales at those stores. I've found that shopping sales at department stores (or better, places like L. L. Bean) is cheaper than a discount retailer and much easier. Even cheaper, go to a thrift store and look for those brands in timeless styles. Your mileage will vary in terms of the what people throw out in your area. Thrift stores work extremely well in high cost of living areas where people give away nearly new items.",
"title": ""
},
{
"docid": "55822",
"text": "The best way to find good quality is to check the garment tag: What kind of material is it made of? Jersey 100% cotton or any 100% cotton is one of the best quality material for most casual clothing. Then, you should touch it (designer step/touching). You will get better along the way. If you think you will like it, it may be a good quality. You should try it. and look for similar material when shopping. It does not matter the store where you shop, you should check the garment quality because even at the expensive stores you can find bad quality. Quality in Stitch: you should check the the garment stitch, look at the top and underneath stitches, watch for good and consist stitching pattern. especially the sides and armholes underneath of the garment. Style is something personal. Everybody has different style, but stores are classified by age targeting. If you can find a store that usually made your style, good quality material at reasonable price. you should consider shop there. Most of the time, it will cost a little bit more or much more. BUT CHEAP IS EXPENSIVE!! you end up spending more money at the end of the year. Reasonable means a fair price for both parties, You and the seller. Neither cheap or expensive.",
"title": ""
},
{
"docid": "158488",
"text": "On the quality angle a big part of it is experience, but the biggest thing is careful observation. You have to take a close, critical look at any article of clothing. (This holds true for just about any purchase.) As far as finding them for reasonable prices it's the usual thing: sales and buying them second-hand. Finally, regarding maintenance:",
"title": ""
},
{
"docid": "24309",
"text": "The idea that you should buy quality, long lasting clothes shouldn't go unchallenged. It's just not true for everybody. If you have a job or a lifestyle that makes it so your clothes are going to get worn out fast regardless of quality, buying expensive clothes doesn't make sense. With that said: look for heavier-feeling fabrics, avoid colors that will fade (or worse: bleed into your other clothes in the wash). Check the laundry instructions so you can see whether they're on the delicate end of the spectrum. Re: how to extend the life: avoid bleach. Even color safe bleach contains peroxide which can break down fabrics faster.",
"title": ""
}
] |
[
{
"docid": "378319",
"text": "\"I feel the same way too! With two kids, I feel like I am spending what it would cost to run a small country just on clothes, shoes, jackets, replacing everything as it is grown out of! A few things I do: I shop in affordable places and check out sales, and look for the cutest things I can find there in a reasonable price range. If you aren't browsing in the $60 baby dresses, you aren't tempted by them. I don't go looking at $60 shirts for my son, he's five and he doesn't need a $60 shirt. I also really only shop for him two or three times a year for clothing...back to school and early spring are the big ones. For fall I got him five pairs of jeans, maybe 8 tops, new socks, etc. I'll add in a couple of heavier sweatshirts, etc as I go, but I really don't browse for him...it's too easy to find something to buy! I look for inexpensive lines for the things that don't really matter...bright T's for my son for summer that just get dirty and spilled on, sleepers, socks, pj's, etc. Joe Fresh, Walmart, Old Navy, Costco. Then I choose a few things that I know I want brand name or more stylish options for, and find ways to buy them more cheaply. These might be things like logo'd fleece tops, trendy jackets, things where the style is actually noticed. I buy jeans at Old Navy for my son when they are on sale, I buy Gusti/Genevieve LaPierre snowsuits at Sears when they are 40% off in Sept/Oct. The Childrens' Place has good quality, stylish clothing for kids and if you watch, they always have deals on their jeans or tops...then I stock up. And for younger kids, Old Navy and The Children's Place jeans have adjustable waistbands. I've already unrolled cuffs and let out the waist in my son's back to school jeans. I have friends who are starting to take in bags of too-small clothing to consignment shops...if they come away with $100, it's still $100! For preteen and teen kids who want certain brands, etc, I think it is very reasonable to say \"\"we will pay x for each pair of jeans, or x for winter boots. If you want to throw in some babysitting/birthday money and go buy something more expensive, you are welcome to do so!\"\" That way, you are still paying for basics, but they can feel like they aren't stuck wearing things they don't like. Tell them...you can buy 5 tops at $x each for back to school, or 10 tops at $x. And lastly, and most sadly of all: buy less..and stop shopping. There, I said it out loud. I try to be careful of what I buy, but I still find things I bought that were never worn. Now I keep a return basket in laundry/mudroom...if I don't love it, if it seems impractical now that I got it home, if I wanted it just in case item #1 didn't work...it goes in the basket. And I return them. I suck it up, I take it with me and go get my money back. Mistakes can be fixed if the items haven't been worn or washed.\"",
"title": ""
},
{
"docid": "290782",
"text": "\"Zero? Ten grand? Somewhere in the middle? It depends. Your stated salary, in U.S. dollars, would be high five-figures (~$88k). You certainly should not be starving, but with decent contributions toward savings and retirement, money can indeed be tight month-to-month at that salary level, especially since even in Cardiff you're probably paying more per square foot for your home than in most U.S. markets (EDIT: actually, 3-bedroom apartments in Cardiff, according to Numbeo, range from £750-850, which is US$1200-$1300, and for that many bedrooms you'd be hard-pressed to find that kind of deal in a good infield neighborhood of the DFW Metro, and good luck getting anywhere close to downtown New York, LA, Miami, Chicago etc for that price. What job do you do, and how are you expected to dress for it? Depending on where you shop and what you buy, a quality dress shirt and dress slacks will cost between US$50-$75 each (assuming real costs are similar for the same brands between US and UK, that's £30-£50 per shirt and pair of pants for quality brands). I maintain about a weeks' wardrobe at this level of dress (my job allows me to wear much cheaper polos and khakis most days and I have about 2 weeks' wardrobe of those) and I typically have to replace due to wear or staining, on average, 2 of these outfits a year (I'm hard on clothes and my waistline is expanding). Adding in 3 \"\"business casual\"\" outfits each year, plus casual outfits, shoes, socks, unmentionables and miscellany, call it maybe $600(£400)/year in wardrobe. That doesn't generally get metered out as a monthly allowance (the monthly amount would barely buy a single dress shirt or pair of slacks), but if you're socking away a savings account and buying new clothes to replace old as you can afford them it's a good average. I generally splurge in months when the utilities companies give me a break and when I get \"\"extra\"\" paychecks (26/year means two months have 3 checks, effectively giving me a \"\"free\"\" check that neither pays the mortgage nor the other major bills). Now, that's just to maintain my own wardrobe at a level of dress that won't get me fired. My wife currently stays home, but when she worked she outspent me, and her work clothes were basic black. To outright replace all the clothes I wear regularly with brand-new stuff off the rack would easily cost a grand, and that's for the average U.S. software dev who doesn't go out and meet other business types on a daily basis. If I needed to show up for work in a suit and tie daily, I'd need a two-week rotation of them, plus dress shirts, and even at the low end of about $350 (£225) per suit, $400 (£275) with dress shirt and tie, for something you won't be embarrassed to wear, we're talking $4000 (£2600) to replace and $800 (£520) per year to update 2 a year, not counting what I wear underneath or on the weekends. And if I wore suits I'd probably have to update the styles more often than that, so just go ahead and double it and I turn over my wardrobe once every 5 years. None of this includes laundering costs, which increase sharply when you're taking suits to the cleaners weekly versus just throwing a bunch of cotton-poly in the washing machine. What hobbies or other entertainment interests do you and your wife have? A movie ticket in the U.S. varies between $7-$15 depending on the size of the screen and 2D vs 3D screenings. My wife and I currently average less than one theater visit a month, but if you took in a flick each weekend with your wife, with a decent $50 dinner out, that's between $260-$420 (£165-270) monthly in entertainment expenses. Not counting babysitting for the little one (the going rate in the US is between $10 and $20 an hour for at-home child-sitting depending on who you hire and for how long, how often). Worst-case, without babysitting that's less than 5% of your gross income, but possibly more than 10% of your take-home depending on UK effective income tax rates (your marginal rate is 40% according to the HMRC, unless you find a way to deduct about £30k of your income). That's just the traditional American date night, which is just one possible interest. Playing organized sports is more or less expensive depending on the sport. Soccer (sorry, football) just needs a well-kept field, two goals and and a ball. Golf, while not really needing much more when you say it that way, can cost thousands of dollars or pounds a month to play with the best equipment at the best courses. Hockey requires head-to-toe padding/armor, skates, sticks, and ice time. American football typically isn't an amateur sport for adults and has virtually no audience in Europe, but in the right places in the U.S., beginning in just a couple years you'd be kitting your son out head-to-toe not dissimilar to hockey (minus sticks) and at a similar cost, and would keep that up at least halfway through high school. I've played them all at varying amateur levels, and with the possible exception of soccer they all get expensive when you really get interested in them. How much do you eat, and of what?. My family of three's monthly grocery budget is about $300-$400 (£190-£260) depending on what we buy and how we buy it. Americans have big refrigerators (often more than one; there's three in my house of varying sizes), we buy in bulk as needed every week to two weeks, we refrigerate or freeze a lot of what we buy, and we eat and drink a lot of high-fructose corn-syrup-based crap that's excise-taxed into non-existence in most other countries. I don't have real-world experience living and grocery-shopping in Europe, but I do know that most shopping is done more often, in smaller quantities, and for more real food. You might expect to spend £325 ($500) or more monthly, in fits and starts every few days, but as I said you'd probably know better than me what you're buying and what it's costing. To educate myself, I went to mysupermarket.co.uk, which has what I assume are typical UK food prices (mostly from Tesco), and it's a real eye-opener. In the U.S., alcohol is much more expensive for equal volume than almost any other drink except designer coffee and energy drinks, and we refrigerate the heck out of everything anyway, so a low-budget food approach in the U.S. generally means nixing beer and wine in favor of milk, fruit juices, sodas and Kool-Aid (or just plain ol' tap water). A quick search on MySupermarkets shows that wine prices average a little cheaper, accounting for the exchange rate, as in the States (that varies widely even in the U.S., as local and state taxes for beer, wine and spirits all differ). Beer is similarly slightly cheaper across the board, especially for brands local to the British Isles (and even the Coors Lite crap we're apparently shipping over to you is more expensive here than there), but in contrast, milk by the gallon (4L) seems to be virtually unheard of in the UK, and your half-gallon/2-liter jugs are just a few pence cheaper than our going rate for a gallon (unless you buy \"\"organic\"\" in the US, which carries about a 100% markup). Juices are also about double the price depending on what you're buying (a quart of \"\"Innocent\"\" OJ, roughly equivalent in presentation to the U.S. brand \"\"Simply Orange\"\", is £3 while Simply Orange is about the same price in USD for 2 quarts), and U.S.-brand \"\"fizzy drinks\"\" are similarly at a premium (£1.98 - over $3 - for a 2-liter bottle of Coca-Cola). With the general preference for room-temperature alcohol in Europe giving a big advantage to the longer unrefrigerated shelf lives of beer and wine, I'm going to guess you guys drink more alcohol and water with dinner than Americans. Beef is cheaper in the U.S., depending on where you are and what you're buying; prices for store-brand ground beef (you guys call it \"\"minced\"\") of the grade we'd use for hamburgers and sauces is about £6 per kilo in the UK, which works out to about $4.20/lb, when we're paying closer to $3/lb in most cities. I actually can't remember the last time I bought fresh chicken on the bone, but the average price I'm seeing in the UK is £10/kg ($7/lb) which sounds pretty steep. Anyway, it sounds like shopping for American tastes in the UK would cost, on average, between 25-30% more than here in the US, so applying that to my own family's food budget, you could easily justify spending £335 a month on food.\"",
"title": ""
},
{
"docid": "217262",
"text": "New clothes isn't exactly an emergency expense :) so I would strongly suggest that you budget for it on a monthly basis. This doesn't mean you have to go spend the money every month, just put a reasonable amount of money into the clothes budget/savings every month and when you need a new shirt or two, take the money out of the saved money and go shopping. If you buy a piece or two of good quality clothing at a time you'd also not run into the situation where all your clothes fall apart at the same time.",
"title": ""
},
{
"docid": "434838",
"text": "\"I buy new clothes when the old ones fall apart, literally. When jeans get holes in the knees, they're relegated to gardening or really messy jobs. Shirts go until they're worn so much that I can't reasonably wear them to work any more. Sounds like your \"\"dress code\"\" at work is about like mine (also a software engineer). I've found that the Dickies jeans and work pants are sturdy, long lasting, fit in reasonably at the workplace, and are very inexpensive. If you know that you're going to need to replace some pants or shirts, wait for a sale to roll around at a local store, and then stock up. I don't specifically budget for clothes since I spend so little. But I'd be at the bottom of anybody's list in terms of giving fashion advice...\"",
"title": ""
},
{
"docid": "302310",
"text": "\"The only thing worse than finding out you are paid less than a co-worker is finding out that you are paid more than all of your co-workers. A lot of people who *think* they would prefer an open and transparent pay-scale (as in unions), change their minds, when placed in one. I have worked in and implemented both types, as both an employee and as an owner/manager. There are pluses and minuses to both. - \"\"Transparent\"\" pay-scale is most effective in a high-turnover, aggressively performance-metric-oriented environment where you expect people to be competing for jobs, including their own job, every day. For example, a pool of commissioned sales-agents: the more you sell, the more you make. Winner gets a Cadillac. Runner-up gets a set of steak knives. Loser gets fired, that kind of thing. If you can't meet your numbers, we let other people start poaching your territory/clients and see what they can do. - Where it doesn't work is in a salary-type position where people are expected to have multiple \"\"soft\"\" duties outside of core performance metrics. The reasons are multi-fold: - One immediate effect of implementing performance-based pay for salary-type employees is that people who are in the office for 8 hours a day, five days a week, immediate start devoting their time and energy towards getting another notch up on the pay-scale, even at the expense of their co-workers, or the company. It intrinsically incentivizes \"\"gaming the system\"\", finding ways to attach your name to easy metrics, and to remove yourself from the most difficult problems. The people who are best at hitting metrics are often not even close to the MVPs. - If instead you take a \"\"soft metrics\"\" or subjective/holistic approach to evaluation, then you get a culture of brown-nosing and office-politics. People start sabotaging the \"\"boss's favorite\"\" and pursuing approval and credit, rather than performance. Instead of fostering a team-oriented, problem-solving approach, it fosters a counter-productive buck-passing, credit-grabbing, and blame-avoidance approach. Note that both of the above intrinsically incentivize risk-avoidance. If you get paid for the number of projects that have your name on them, you find some way to get your name attached to every project, and then move on to the next one, whether the last one was done or not. If you get based on how \"\"successful\"\" the projects bearing your name are, then you avoid anything challenging and make sure only to be attached to the easy ones with the best co-workers. And so on. - Alternately, let's say we keep the same, generic, salary-oriented pay-structure, we just make everyone in a certain \"\"tier\"\" get equal salary, that everyone knows. That sucks all the life out of everyone's sails so fast it will make your head spin: you cannot get a raise for doing a better job, you get paid the same raise as your worst co-worker, every year, for as long as you work here. We will never cut your pay, all you have to do is not be the canary in the coalmine-- so long as you can identify the worst performer in your group, and so long as it's not you, your job is safe. What time do you have to arrive? 5 minutes earlier than the latest-arriving person. How early can you leave? 5 minutes after the earliest one to check out. How much work do you have to get done? Only as much as anyone else is doing. What will you get for being the hardest-working, earliest-to-arrive, latest-to-leave? The same as the worst performer gets: you'll be splitting your raise with him, since we don't credit individuals here, just job-titles. Most jobs that can be easily automated, are automated. If you need a human employee to do it, it's usually because it involves a nontrivial amount of \"\"soft\"\" skills and fuzzy-logic type thinking and behavior. A machine programmed purely to make as many widgets per hour as possible, and motivated to so with human-style skills, ingenuity, and incentives, will tear down the whole factory and dismantle all its co-workers and ignore all quality-controls in order to keep producing widgets. You can't reduce human beings to input-process-output flowcharts (or rather you can, but they will invariably find unintended ways to outsmart your design criteria, with unintended consequences). The reason you need a person instead of an automated process is because you need a whole host hard-to-define, soft/fuzzy/flexible critical-thinking type skills. **Everyone's job seems easier to the people who don't have to do it, and there is a tremendous hidden danger to de-valuing personal desire to do a subjectively \"\"good job\"\" by quantifying/genericizing the value of their contribution.** Personnel management is very difficult to reduce to an engineering problem. You usually need good managers who can identify and motivate good employees, who will feel lucky to have the job and the salary they have, and who will come in every day trying to earn it. Posting everyone's pay on a bulletin-board negates all those \"\"soft\"\" skills, by putting a quantified, black-and-white, relative value on everyone's contribution. Even in a very large organization, the \"\"marketplace\"\" of employees is rarely large enough, and the quality of real-time metrics is almost never good enough to \"\"digitize\"\" the bell-curve of employee performance. You end up making it a square-wave that demotivates all but the most extreme outliers.\"",
"title": ""
},
{
"docid": "47542",
"text": "Zhongshan Opaye Industry Co.,Ltd. is a professional home appliances manufacturer in China. Opaye company is a one of the leading companies to produce the professional portable clothes dryer, electric thermo pot, electric water boiler, electric kettle, soymilk maker, juice extractor, slow juicer, screw juice extractor, soup maker, commercial blender, food processor etc. Opaye's products are sold well in worldwide markets, including the USA, Europe,Southeast Asia, Japan and Taiwan area. Opaye keeps the stable business relationships with such our world partners as Metro Germany, Sunbeam Europe and QVC UK. As an ISO9001/2000 certified company, opaye is highly focused on quality control, just-in-time delivery, cost control,provision of innovative and tailored products and good service to attain total customer satisfaction and maintain a win-win relationship with customers on a long-term basis. As a must to enter our target markets, most of our products are CE/GS, ETL, CB and CCC approved and Rosh compliant. To keep our advantage in the industry,we registered technology and design patent for our products and keep improving our quality and production efficiency. The in-house tooling workshop, metal department, plastic injection department and more than 1000 workers enable our cost efficiency and productivity. Repeating orders by our clients is the best proof that we have matched their demands in terms of quality and reliability. Welcome and find out how you will enjoy working with Opaye. Further information pls feel free to visit our website: www.opaye.com",
"title": ""
},
{
"docid": "291334",
"text": "At Pop Up Tee, you can find a wide range of gym t-shirts available in different styles and designs. Wearing right clothing for your gym sessions can help you last long hours and furthermore protect your health. Needless to say, you can look extremely fashionable with our gym t-shirts.",
"title": ""
},
{
"docid": "285836",
"text": "The way I handle clothing purchases, is I save a little bit with each paycheck but don't commit to spending each month. I wait until I find the exact item I need or know I will need in the near future. I have a list of things to look for so I don't get off track and blow my budget. And each time I consider hitting Starbucks or buying a random something at Target, I think which is a better investment - a great pair of pants that will work for me for a decade, or a latte? Thank you for linking to me. Your question is one many people have. I feel that clothing should be purchased slowly, with care. If you do it this you will buy items that don't need to be replaced every two years, and will maintain style and quality longer. :)",
"title": ""
},
{
"docid": "549601",
"text": "I know of no generic formula for determining if an investment property is a good investment, besides the trivial formula. Make sure your income is greater than your expenses, and hope the value of the property doesn't drop. Some people will tell you to expect the monthly rent to be a fixed percentage of the purchase price, but that is a goal not a certainty. It is also impossible to estimate the difficulty renting the property, or how long the roof will last. Taxes can't be predicted, as the value of the house increase, so do the property taxes, but you might not be able to increase the rent. You can't even predict the quality of the tenant. Will they damage the property? Or skip out early? You will need somebody who knows the local market to estimate the local conditions, and help you determine the estimated costs and income based on the actual property involved.",
"title": ""
},
{
"docid": "360059",
"text": "\"There are people (well, companies) who make money doing roughly what you describe, but not exactly. They're called \"\"market makers\"\". Their value for X% is somewhere on the scale of 1% (that is to say: a scale at which almost everything is \"\"volatile\"\"), but they use leverage, shorting and hedging to complicate things to the point where it's nothing like a simple as making a 1% profit every time they trade. Their actions tend to reduce volatility and increase liquidity. The reason you can't do this is that you don't have enough capital to do what market makers do, and you don't receive any advantages that the exchange might offer to official market makers in return for them contracting to always make both buy bids and sell offers (at different prices, hence the \"\"bid-offer spread\"\"). They have to be able to cover large short-term losses on individual stocks, but when the stock doesn't move too much they do make profits from the spread. The reason you can't just buy a lot of volatile stocks \"\"assuming I don't make too many poor choices\"\", is that the reason the stocks are volatile is that nobody knows which ones are the good choices and which ones are the poor choices. So if you buy volatile stocks then you will buy a bunch of losers, so what's your strategy for ensuring there aren't \"\"too many\"\"? Supposing that you're going to hold 10 stocks, with 10% of your money in each, what do you do the first time all 10 of them fall the day after you bought them? Or maybe not all 10, but suppose 75% of your holdings give no impression that they're going to hit your target any time soon. Do you just sit tight and stop trading until one of them hits your X% target (in which case you start to look a little bit more like a long-term investor after all), or are you tempted to change your strategy as the months and years roll by? If you will eventually sell things at a loss to make cash available for new trades, then you cannot assess your strategy \"\"as if\"\" you always make an X% gain, since that isn't true. If you don't ever sell at a loss, then you'll inevitably sometimes have no cash to trade with through picking losers. The big practical question then is when that state of affairs persists, for how long, and whether it's in force when you want to spend the money on something other than investing. So sure, if you used a short-term time machine to know in advance which volatile stocks are the good ones today, then it would be more profitable to day-trade those than it would be to invest for the long term. Investing on the assumption that you'll only pick short-term winners is basically the same as assuming you have that time machine ;-) There are various strategies for analysing the market and trying to find ways to more modestly do what market makers do, which is to take profit from the inherent volatility of the market. The simple strategy you describe isn't complete and cannot be assessed since you don't say how to decide what to buy, but the selling strategy \"\"sell as soon as I've made X% but not otherwise\"\" can certainly be improved. If you're keen you can test a give strategy for yourself using historical share price data (or current share price data: run an imaginary account and see how you're doing in 12 months). When using historical data you have to be realistic about how you'd choose what stocks to buy each day, or else you're just cheating at solitaire. When using current data you have to beware that there might not be a major market slump in the next 12 months, in which case you won't know how your strategy performs under conditions that it inevitably will meet eventually if you run it for real. You also have to be sure in either case to factor in the transaction costs you'd be paying, and the fact that you're buying at the offer price and selling at the bid price, you can't trade at the headline mid-market price. Finally, you have to consider that to do pure technical analysis as an individual, you are in effect competing against a bank that's camped on top of the exchange to get fastest possible access to trade, it has a supercomputer and a team of whizz-kids, and it's trying to find and extract the same opportunities you are. This is not to say the plucky underdog can't do well, but there are systematic reasons not to just assume you will. So folks investing for their retirement generally prefer a low-risk strategy that plays the averages and settles for taking long-term trends.\"",
"title": ""
},
{
"docid": "137226",
"text": "\"I hear you (and those answering) use the words \"\"my money\"\" (or \"\"me to pay for stuff\"\") The sooner that ends, the better off you'll both be. My wife and I do have our own checking accounts that we maintain so she can write a check without notifying me, or I can buy her a birthday/mother's day/ etc gift without it showing in the joint account, but nearly all money flows through our joint account. Before we were married, the joint bank accounts were opened as was the joint brokerage account. You need to work on the budget as a single project and without judging. It's good that your incomes are similar, it makes the dynamics of pooling seem more fair, but for those where one spouse is making far more than the other, the impulse to 'chip in' equally towards bills leaves the lower earner with nothing. Will your wife go back to work after a maternity leave? Once she's back, and working for a time, things will settle down a bit. There's a postpartum time that's difficult. Women who have been through it will tell you that it can be pretty bad, and the best a guy can do is be understanding and supportive. As long as you are talking \"\"we\"\" with your wife, she'll see that you are both in it together. At the risk of sounding sexist, Women's clothing needs are different than men's. I could get away with owning 5 suits which could be replaced at the rate of one per year. If not for my wife, I can see in my own daughter how clothing makes her feel good about herself, and while I'm frugal with most of our budget, my clothing questions are 2 - Will it last? & Will it match other pieces you have? Therefore, clothing gets a line item all its own in the budget. There are a number of financial things to consider, but I see you are in the UK, so I'll generalize. In the States, there are pretax benefits to help care for a child under 13 (called a dependent care account) and for medical expenses not covered by insurance (called flexible spending account). These let you take money from your pay pretax to use for specific expenses. If UK offers similar, I invite a user to edit the detail into my answer. Last - once the kid comes into our lives, there's little room for many of the late teen/early 20's spending. Comics? DVDs? Those are the low hanging fruit of wasted money. Saving for retirement, and for University for the kid take priority. I'm not one to quote cliches but a friend once offered this observation - \"\"If you are not happy but your wife is happy, you are still far happier than if you were happy but your wife is not happy.\"\"\"",
"title": ""
},
{
"docid": "446208",
"text": "\"The Craftsman brand is the only thing that Sears has that is worth anything. Despite Sears' many woes, the Craftsman name is still about as close to \"\"golden\"\" as you can get in the tool world. Sears still know knows how to source and purchase top-notch product. Sears is one of the few companies out there that still has an in-house, staffed, top tier professional testing lab that doesn't just drop the tool on the floor to see if it breaks. Alas, that isn't the whole story. Everyone else is in the private labeling gig as well. Home Depot has Husky. Lowes has Kobalt. Problem is that those \"\"other guys\"\" ARE sourcing mediocre warez from China at a much lower cost. We all know how much Americans like cheap shit. 90% of the weekend warriors want to buy a \"\"pretty good\"\" tool. They don't want to pay 2x or 3x the price for something of superior quality that will last a VERY long time (such as the Craftsman brand of yesteryear). Even though that Craftsman tool was of superior quality, they were losing sales left and right to the \"\"pretty good\"\" stuff at other stores that cost half the price. Sears had no chance but to cut costs and quality in order to stay competitive. Having the best quality stuff on the market is no longer enough to stay in business. The DIY hardware/tool market doesn't support that angle any more. Walk inside of a Harbor Freight. Some of that stuff is borderline junk. However, it's good enough for many people that only need a tool or two to get them through a quick fix. This is the new consumer market - \"\"Just good enough for today and maybe tomorrow\"\".\"",
"title": ""
},
{
"docid": "335164",
"text": "\"My education on this topic at this age range was a little more free-form. We were given a weeklong project in the 6th grade, which I remember pretty clearly: Fast forward 6 years (we were 12). You are about to be kicked out of your parents' house with the clothes on your back, $1,000 cash in your pocket, your high school diploma, and a \"\"best of luck\"\" from your parents. That's it. Your mission is to not be homeless, starving and still wearing only the clothes on your back in 3 months. To do this, you will find an apartment, a job (you must meet the qualifications fresh out of high school with only your diploma; no college, no experience), and a means of transportation. Then, you'll build a budget that includes your rent, estimated utilities, gasoline (calculated based on today's prices, best-guess fuel mileage of the car, and 250% of the best-guess one-way distance between home and job), food (complete nutrition is not a must, but 2000cal/day is), toiletries, clothing, and anything else you want or need to spend your paycheck or nest egg on. Remember that the laundromat isn't free, and neither is buying the washer/dryer yourself. Remember most apartments aren't furnished but do have kitchen appliances, and you can't say you found anything on the side of the road. The end product of your work will be a narrative report of the first month of your new life, a budget for the full 3 months, plus a \"\"continuing\"\" budget for a typical month thereafter to prove you're not just lasting out the 3 months, and all supporting evidence for your numbers, from newspaper clippings to in-store mailers (the Internet and e-commerce were just catching on at the time, Craigslist and eBay didn't exist yet, and not everyone had home Internet to begin with). Extra Credit: Make your budget work with all applicable income and sales taxes. Extra Extra Credit: Have more than your original $1000 in the bank at the end of the 3 months, after the taxes in the Extra Credit. This is a pretty serious project for a 12-year-old. Not only were we looking through the classified ads and deciphering all the common abbreviations, we were were taking trips to the grocery store with shopping lists, the local Wal-Mart or Target, the mall, even Goodwill. Some students had photos of their local gas station's prices, to which someone pointed out that their new apartment would be on the other side of town where gas was more expensive (smart kid). Some students just couldn't make it work (usually the mistakes were to be expected of middle-class middle-schoolers, like finding a job babysitting and stretching that out full-time, only working one job, buying everything new from clothes to furniture, thinking you absolutely need convenience items you can do without, and/or trying to buy the same upscale car your dad takes to work), though most students were able to provide at least a plausible before-tax budget. A few made the extra credit work, which was a lot of extra credit, because not only were you filling out a 1040EZ for your estimated income taxes, you were also figuring FICA and Social Security taxes which even some adults don't know the rates for, and remember, no Internet. Given that the extra-extra credit required you to come out ahead after taxes (good luck), I can't remember that anyone got that far. The meta-lesson that we all learned? Life without a college education is rough.\"",
"title": ""
},
{
"docid": "420046",
"text": "You should be worried. You have made the mistake of entering an investment on the recommendation of family/friend. The last think you should do is make another mistake of just leaving it and hoping it will go up again. Your stock has dropped 37.6% from its high of $74.50. That means it has to go up over 60% just to reach the high of $74.50. You are correct this may never happen or if it does it could take a long, long time to get up to its previous highs. What is the company doing to turn its fortunes around? Take a look at some other examples: QAN.AX - Qantas Airways This stock reached a high of around $6 in late 2007 after a nice uptrend over a year and a half, it then dropped drastically at the start of the GFC, and has since kept falling and is now priced at just $1.15. QAN reported its first ever loss earlier this year, but its problems were evident much earlier. AAPL - Apple Inc. AAPL reach a high of just over $700 in September 2013, then dropped to around $400 and has recovered a bit to about $525 (still 25% below its highs) and looks to be at the start of another downtrend. How long will it take AAPL to get back to $700, more than 33% from its current price? TEN.AX - Ten Network Holdings Limited TEN reached a high of $4.26 in late 2004 after a nice uptrend during 2004. It then started a steep journey downwards and is still going down. It is now priced at just $0.25, a whopping 94% below its high. It will have to increase by 1600% just to reach its high of $4.26 (which I think will never happen). Can a stock come back from a drastic downtrend? Yes it can. It doesn't always happen, but a company can turn around and can reach and even surpass it previous highs. The question is how and when will this happen? How long will you keep your capital tied up in a stock that is going nowhere and has every chance of going further down? The most important thing with any investment is to protect your current capital. If you lose all your capital you cannot make any new investments until you build up more capital. That is why it is so important to have a risk management strategy and decide what is your get out point if things go against you before you get into any new investment. Have a stop loss. I would get out of your investment before you lose more capital. If you had set a stop loss at 20% off the stock's last highs, you would have gotten out at about $59.60, 28% higher than the current share price of $46.50. If you do further analysis on this company and find that it is improving its prospects and the stock price breaks up through its current ranging band, then you can always buy back in. However, do you still want to be in the stock if it breaks the range band on the downside? In this case who knows how low it can continue to go. N.B. This is my opinion, as others would have theirs, and what I would do in your current situation with this stock.",
"title": ""
},
{
"docid": "497329",
"text": "True, but shitty products is how they get their fuck all pricing. Say what you will for the virtue of quality, but at least it's an ethos for a sustainable business. How long do you think Amazon can sustain these prices?",
"title": ""
},
{
"docid": "535688",
"text": "\"One of the best answers to this question that I've ever read is in a paper published by Robert Lucas in the Journal of Economic Perspectives. That journal is meant to a be a place for experts to write about their area of expertise (in economics) for a general but still technically-minded audience. They recently opened up the journal as free to the public, which is a fantastic resource -- you no longer need a subscription to JSTOR (or whatever) to read it. You can read the abstract to the paper, and find a link to it, here. One of the things that I like a lot about this paper is that it strips out absolutely everything even slightly unnecessary to thinking about a macroeconomy, and just discusses what one can arrive at with a very very simple model. Of course, with great simplicity come sacrifice about details. However, it does a great job of answering your question, \"\"why do people care about growth?\"\" A quick note: the key to understanding the answer to your question is to think about things in terms of \"\"the long term\"\" -- not even looking forward to the future, because we'll be dead by then, but looking back to the past. The key to the importance of growth is that, for the last ~200 years, the US has, on average, had maybe 2-3% \"\"real growth\"\" per year (I'm pulling these numbers out of my head; I think much better numbers are in that paper somewhere). On average, over that period of time, this growth has meant that the quality of life that one has, if one lives in a country experiencing this growth, is enormous compared to countries that do not experience this average growth over that period. Statistically speaking, growth is also somewhat auto-correlated. Roughly speaking, if it was low the last few periods, you can expect it to be low the next period. Same thing if it's high. Then, the reason we care about growth right now: if you have too many periods of low growth, pretty soon the average \"\"over the long term\"\" growth will be pulled down -- and then quality of life can't be higher in the future (which quickly becomes someone's \"\"present\"\"). The paper above makes this point with a very simple model. Of course, none of this touches on distributional issues, which are another issue entirely. With respect to, \"\"The economy needs to grow to just keep up with its debt repayments,\"\" I think the answer is along the lines of, \"\"sometimes countries get into debt expecting that growth will increase their resources in the future, and thus they can pay back their debt.\"\" That strategy is, of course, the strategy that anyone borrowing (\"\"taking out a loan\"\") should be employing -- you should expect that your future income will be enough to pay back your interest+principle on a loan you took. Otherwise you're irresponsible. At the aggregate level, production is the nation's \"\"income\"\" -- it is what you have, all that you have (as a nation) to pay back any debt you've incurred at the national level.\"",
"title": ""
},
{
"docid": "262447",
"text": "\">You don't want FDA to review generic applications? I don't want there to be \"\"applications,\"\" period. People and their doctors are the best judge of what substances should be consumed for health reasons. >How would you stop fly by night companies from selling low quality harmful drugs? I wouldn't. And yet, the best examples of \"\"harmful drugs\"\" out there, such as heroin, cocaine, etc have all gotten significantly more pure over time without government intervention. Consumers for some magic reason are demanding and receiving better quality drugs! How is that happening? Let me reverse the question for you - why do you want to artificially limit supply of drugs to people, driving up prices? What good does that serve?\"",
"title": ""
},
{
"docid": "334654",
"text": "The best way to save on clothes is up to you. I have friends who save all year for two yearly shopping trips to update anything that may need updating at the time. By allowing themselves only two trips, they control the money spent. Bring it in cash and stop buying when you run out. On the other hand in my family we shop sales. When we determine that we need something we wait until we find a sale. When we see an exceptionally good sale on something we know we will need (basic work dress shoes, for example), we'll purchase it and save it until the existing item it is replacing has worn out. Our strategy is to know what we need and buy it when the price is right. We tend to wait on anything that isn't on sale until we can find the right item at a price we like, which sometimes means stretching the existing piece of clothing it is replacing until well after its prime. If you've got a list you're shopping from, you know what you need. The question becomes: how will you control your spending best? Carefully shopping sales and using coupons, or budgeting for a spree within limits?",
"title": ""
},
{
"docid": "561205",
"text": "Let's clarify some things. Companies allow for the public to purchase their shares through Initial Public Offering (IPO) (first-time) and Seasoned Public Offering (SPO) (all other times). They choose however many shares they want to issue depending on the amount of capital they want to raise. What this means is that the current owners give up some ownership % in exchange for cash (usually). In the course of IPOs and SPOs, it can happen that the public will not buy all shares if there is very little interest, but I would assume that the more probable scenario if very little interest is present is that the shares' value would take a big drop on their issuance date from the proposed IPO/SPO price. After those shares are bought by the public, they are traded on Exchanges which are a secondary and (mostly) do not affect the underlying company. The shares are exchanged from John Doe to Jane Doe as John Doe believes the market value for those shares will take a direction that Jane Doe believes in the opposite. Generally speaking, markets will find an equilibrium price where you can reasonably easily buy-sell securities as the price is not too far from what most participants in the market believe it should be. In cases where all participants agree on the direction (most often in case of a crash) it can be hard to find a party to make a trade with. Say a company just announced negative news with long-lasting effects on the business there will be a surge in sell orders with very few buyers. If you are willing to buy, you will likely very easily find a trading partner but if you are trying to sell instead then you will have to compete for the lowest price against all other sellers. All that to say that in such cases, while shares are technically sellable / purchasable, the end result can be that no shares are purchasable.",
"title": ""
},
{
"docid": "63980",
"text": "To be honest, if you have to ask tips about taking over your family business, someone really dropped the ball on showing you the business in the first place. Anyway, learn yourself some basic bookkeeping/accounting. Money management/tax handling will be something you will need to know, even if you have staff to handle this for you. Learn the specific product/service/whatever you offer. Nothing can be worse than having no clue what your product/service does and you're running it. Shadow the family member(s) that are running it now. Find out what they do throughout their day involving the business. Whoever your replacing is the one you should focus on most. Also make sure you understand your branding, quality, and price measures. Any basic business class will teach you that branding, quality, and price are the three factors of a business's success. Where you fail in one, you take up in another. For instance, Apple has horrible prices. Extremely expensive. How do they make it up? Well, quality is about on par with other products (since they largely come from the same source as competitors), but the iPhone and iPod are well known brands (far more recognized than the smartphone and MP3 player that they are, instead called by the specific product name). Same with Kleenex. No one asks for a facial tissue. They ask for a Kleenex. That's strong branding that connects the consumer to the product. Anyway, just make sure you know where your points fall on those three lines in your business. Improve as you can, but understand where your main fall back is. Best prices, quality, or most well known? Lastly, don't doubt that you can do this. Similarly, don't overcompensate. Your friends will all ask for deals and discounts and you'd do best to deny them in most cases. Family will always want a cut and will probably get nasty in some cases (mattering by how you're set up). When dealing with employees, remember that they work for you: You're not friends. Nothing destroys a staff faster than the boss trying to be friends with everyone and ends up promoting the schmoozer. Eh, not sure what else to toss out. That covers a lot of bases, but I'm sure I can think of more later.",
"title": ""
},
{
"docid": "186804",
"text": "\"I encourage you to think of this home purchase decision as a chance to buy into a community that you want your children to grow up in. Try to find a place where you will be happy for the next 20 years, not just the next 2 or 7 years. In your situation, option 1 seems like a bad idea. It will create an obstacle to having children, instead of establishing a place for them to grow up in. Option 2 is close to \"\"buying a house on a layaway plan\"\". It offers the most financial flexibility. It also could result in the best long-term outcome, because you will buy in an established area, and you will know exactly what quality house you will have. But you and your fiancé need to ask yourselves some hard questions: Are you willing to put up with the mess and hassles of remodelling? Are you good at designing such projects? Can you afford to pay for the projects as they occur? Or if you need to finance them, can you get a HELOC to cover them? Especially if you and your fiancé do much of the work yourselves, break down the projects into small enough pieces that you can quickly finish off whatever you are working on at the time, and be happy living in the resulting space. You do not want to be nagging your husband about an unfinished project \"\"forever\"\" -- or silently resenting that a project never got wrapped up. I posted some suggestions for incrementally finishing a basement on the Home Improvement Stack Exchange. If you are up to the job of option 2, it is less risky than option 3. Option 3 has several risks: You don't know what sort of people will live in the neighborhood 5 - 20 years from now. Will the homes be owner-occupied? Or rentals? Will your neighbors care about raising children well? Or will lots of kids grow up in broken homes? Will the schools be good? Disappointing? Or dangerous? Whereas in an established neighborhood, you can see what the neighborhood is currently like, and how it has been changing. Unless you custom-build (or remodel), you don't control the quality of the construction. Some neighborhoods built by Pulte in the last 10 years were riddled with construction defects. You will be paying up-front for features you don't need yet. You might never need some of them. And some of them might interfere with what you realize later on might be better. In stable markets, new homes (especially ones with lots of \"\"upgrades\"\") often decline in value during the first few years. This is because part of the value is in the \"\"newness\"\" and being \"\"up-to-date\"\" with the latest fads. This part of the value wears off over time. Are the homes \"\"at the edge of town\"\" already within reasonable walking distance of parks, schools, church, grocery stores, et cetera? Might the commute from the \"\"edge of town\"\" to work get worse over the next 5 - 20 years?\"",
"title": ""
},
{
"docid": "422183",
"text": "\"I don't agree that the market as a whole is a ponzi scheme, but there are some ponzi-like aspects to it. If you buy high quality stocks like Coca Cola, Johnson and Johnson, AT&T, Verizon, Kraft, Wells Fargo (the vanilla bank, not one of the crazy ones), IBM, Berkshire Hathaway etc and simply hold onto them for the next 10-20 years, you will make money. Even over the last decade, when stocks \"\"went nowhere\"\", you still came out ahead through the dividend payments. It was just at an unsatisfactory rate of return. Also \"\"the market\"\" consists of a lot more than just stocks. Corporate bonds are a big market and I always recommend people to look at bonds. If you cannot judge whether a company is credit worthy, how can you invest in the common stock? I've made a lot more money myself in the bond market than in the stock market. However, for many stocks, they do look a lot like ponzi schemes. This is true, in particular, with many of the tech stocks (Cuban was a tech investor, so that is probably where his sentiment is coming from). You have many of these companies that create great products. However, they never have positive cash flow because all the money is spent to develop new products. As the share price goes up, the company issues new shares to fund research, stock options to employees to enrich them, etc. However, eventually, they run into a string of bad research that do not yield a new product and the share price plunges. Perhaps the company goes bankrupt. So you have a company that developed great products, but the shareholders never got a penny in dividends and the final shareholders have paper worth zero. Take a look at Research in Motion for example. Creating the Blackberry has to be one of the biggest successes in tech over the last decade. However, has the shareholders gotten any richer? Only if they traded amongst themselves, nobody got a dividend. What happened to the many billions of dollars they made during the peak popularity years of Blackberry? It went to executives, employees, and was squandered on development that did not effectively defend the phone's dominant market position. Now the stock price is back down to the pre-prime years, and if a shareholder held onto it throughout the entire period, he would not have received a single penny. And this is a profitable enterprise, things look even more bizarre when you start looking at the tech companies that have NEVER had a positive earnings quarter and no plans to ever have positive earnings (something like Pandora comes to mind). Often, management at these more bizarre companies run the company as a toy - to play with their own ideas and to issue themselves stock as compensation. And of course, they sell a lot of the stock to cash in before they delve into the next risky venture. They have no intention of ever enriching anybody who holds into the stock in the long run. If for some reason they make money, they will put it all into their next toy project until one of them fails and wipes everything out. If you invest in a profitable business with reasonable management, you will generally come out ahead. Some businesses get displaced by unpredictable circumstances and they go bankrupt. But on average, if a company is good at doing something and they pay out the earnings, you come out ahead. You get in trouble when businesses are good at something, and they take all the money they make and put it into doing something they are not good at. A business might only provide good cashflow for 10-20 years when the product is popular and before competitors cut into margins. If that money is squandered, the long term shareholder may ultimately have very terrible results. The long term shareholder ends up being the guy who keeps going all-in on a 80%-chance-to-win bet (that is what management is doing when they bet the company on the next unproven product), but eventually he gets zeroed out on one loss. This is why if you look at Buffett's investments, they are all in simple businesses that spits off cash to the owner/shareholder. Businesses like soft drinks, snacks, rail roads, vanilla banking, utility-like energy companies, insurance, etc. You might be good at judging the odds of whether a business will succeed or not (aka make more money than your original investment or not). But you don't want management of that company to make a wildly different bet for you. Just because they are great at operating a company doesn't mean they are good enough at judging odds or disciplined enough to make those bets for you. I may have predicted accurately that Business X will be a great success, but if manage takes those profits and goes all in on Business Y, without giving me a chance to cash out, that may have disasterous results.\"",
"title": ""
},
{
"docid": "368074",
"text": "\">If we could provide medicine, food, clothing, shelter, and internet access to every person in the country, then it hardly matters how callous and Randian the employment market is. We can already provide medicine, food, clothing, shelter and internet access to every person in the country, for your implied price of more-or-less free. Our GDP per capita versus our prices is high enough that a basic income program and a universal health-care program could pretty much *solve* the fundamental economic problems of life (in the \"\"how do I not die on the street?\"\" sense). Capitalism in the Randian sense *is what stops us from doing so*.\"",
"title": ""
},
{
"docid": "388912",
"text": "\"This article is interesting, but deeply biased. The writer manages to write pages and pages on a feature about Charney that only tells Charney's story. He interviews (I think, unless he's always just quoting other sources) a few other folks, but only ones who think he's brilliant and was wronged. It was only in the last 25% (of a very long article) when the author even bothers to reference the criticisms and discussion of sexual harassment and culture of sexualizing women that was part of what started the blowback from customers, and though it says something like \"\"You can't talk about Charney's story without mentioning the sexuality,\"\" it seems like an afterthought. Basically, \"\"a lot of people said Charney was a creep, and some of them sued him, but he says the allegations are false so let's move on.\"\" It wasn't just increasingly uncomfortable ads, it was also people saying they were coerced into those ads, people saying the workplace was almost toxic in it's sexual charge, Charney saying stuff like \"\"then they shouldn't work here,\"\" the fact that people working in the stores were rated on their attractiveness and size, that AA wouldn't make or sell clothes past a certain size because he didn't want large people wearing his clothes, the fact that the clothes cost $50 for a tee shirt then fell apart, etc. Charney certainly has his side of things, but I personally think it was irresponsible to write a feature this long without giving more than a paragraph or two of context into why it wasn't just a cruel board doing him wrong, but that even many of his employees and customers turned away from the brand.\"",
"title": ""
},
{
"docid": "109292",
"text": "\"I agree that you should CONSIDER a shares based dividend income SIPP, however unless you've done self executed trading before, enough to understand and be comfortable with it and know what you're getting into, I would strongly suggest that as you are now near retirement, you have to appreciate that as well as the usual risks associated with markets and their constituent stocks and shares going down as well as up, there is an additional risk that you will achieve sub optimal performance because you are new to the game. I took up self executed trading in 2008 (oh yes, what a great time to learn) and whilst I might have chosen a better time to get into it, and despite being quite successful over all, I have to say it's the hardest thing I've ever done! The biggest reason it'll be hard is emotionally, because this pension pot is all the money you've got to live off until you die right? So, even though you may choose safe quality stocks, when the world economy goes wrong it goes wrong, and your pension pot will still plummet, somewhat at least. Unless you \"\"beat the market\"\", something you should not expect to do if you haven't done it before, taking the rather abysmal FTSE100 as a benchmark (all quality stocks, right? LOL) from last Aprils highs to this months lows, and projecting that performance forwards to the end of March, assuming you get reasonable dividends and draw out £1000 per month, your pot could be worth £164K after one year. Where as with normal / stable / long term market performance (i.e. no horrible devaluation of the market) it could be worth £198K! Going forwards from those 2 hypothetical positions, assuming total market stability for the rest of your life and the same reasonable dividend payouts, this one year of devaluation at the start of your pensions life is enough to reduce the time your pension pot can afford to pay out £1000 per month from 36 years to 24 years. Even if every year after that devaluation is an extra 1% higher return it could still only improve to 30 years. Normally of course, any stocks and shares investment is a long term investment and long term the income should be good, but pensions usually diversify into less and less risky investments as they get close to maturity, holding a certain amount of cash and bonds as well, so in my view a SIPP with stocks and shares should be AT MOST just a part of your strategy, and if you can't watch your pension pot payout term shrink from 26 years to 24 years hold your nerve, then maybe a SIPP with stocks and shares should be a smaller part! When you're dependent on your SIPP for income a market crash could cause you to make bad decisions and lose even more income. All that said now, even with all the new taxes and loss of tax deductible costs, etc, I think your property idea might not be a bad one. It's just diversification at the end of the day, and that's rarely a bad thing. I really DON'T think you should consider it to be a magic bullet though, it's not impossible to get a 10% yield from a property, but usually you won't. I assume you've never done buy to let before, so I would encourage you to set up a spread sheet and model it carefully. If you are realistic then you should find that you have to find really REALLY exceptional properties to get that sort of return, and you won't find them all the time. When you do your spread sheet, make sure you take into account all the one off buying costs, build a ledger effectively, so that you can plot all your costs, income and on going balance, and then see what payouts your model can afford over a reasonable number of years (say 10). Take the sum of those payouts and compare them against the sum you put in to find the whole thing. You must include budget for periodic minor and less frequent larger renovations (your tenants WON'T respect your property like you would, I promise you), land lord insurance (don't omit it unless you maintain capability to access a decent reserve (at least 10-20K say, I mean it, it's happened to me, it cost me 10K once to fix up a place after the damage and negligence of a tenant, and it definitely could have been worse) but I don't really recommend you insuring yourself like this, and taking on the inherent risk), budget for plumber and electrician call out, or for appropriate schemes which include boiler maintenance, etc (basically more insurance). Also consider estate agent fees, which will be either finders fees and/or 10% management fees if you don't manage them yourself. If you manage it yourself, fine, but consider the possibility that at some point someone might have to do that for you... either temporarily or permanently. Budget for a couple of months of vacancy every couple of years is probably prudent. Don't forget you have to pay utilities and council tax when its vacant. For leaseholds don't forget ground rent. You can get a better return on investment by taking out a mortgage (because you make money out of the underlying ROI and the mortgage APR) (this is usually the only way you can approach 10% yield) but don't forget to include the cost of mortgage fees, valuation fees, legal fees, etc, every 2 years (or however long)... and repeat your model to make sure it is viable when interest rates go up a few percent.\"",
"title": ""
},
{
"docid": "127015",
"text": "There are several reasons why this may happen and I will update as I get more information from you. Volumes on that stock look low (supposing that they are either in a factor between 1s and 1000s) so it could well be that there was no volume on that day. If no trades occur then open, high and low are meaningless as they are statistics based on trades that occur that day and no trades occur. Remember that there has to be volume to get a price. The stock may have been frozen by either the exchange or the company for the day. This could be for various reasons including to prevent some illegal activity. In that case no trades were made because the market for that stock was closed. Another possibility is that all trades that day were cancelled by the exchange. The exchange may cancel all trades if there is unusual, potentially fraudulent or other illegal activity on the stock. In this case the last price for that day existed but was rolled back by the exchange and never occurred. This is a rare situation. Although I can't find any holidays on that date it is possible that this is how your data provider marks market holidays. It would be valid to ignore the data in that case as being from a non-market day. I cannot tell if this is possible without knowing exchange information. There is a possibility that some data providers don't receive data for a day or that it gets corrupted. It may be worth checking another source to ensure the integrity of the data that you are receiving. Whichever reason is true, the data provider has made the close equal to the previous day's close as no price movements occurred. Strictly the closing price is the price of the last trade made for that day and so should be null (and open, high and low should be null too and not 0 otherwise the price change on day is very large!). Therefore, to keep integrity, you have a few choices:",
"title": ""
},
{
"docid": "543945",
"text": "\"You don't even need to wear special or sexy cloths. Just be \"\"nice\"\" to the right people, and, especially with women, it will work wonders. P/S: I would also add that you don't even need to be very good at your work if you are being \"\"nice\"\". Just be reasonable and average with the quality of your work.\"",
"title": ""
},
{
"docid": "479762",
"text": "\"Just to really drive home how wrong you are, let's review both: **Government** - you get 1 single binary choice every 2, 4 or 6 years not on an actual decision but for another PERSON to make the choices for you, without your input from then on, without any liability. If they lie to win their election, there's nothing you can do. There was no contract. You get no refund. They have control over the 1/3 of your income that taxation gives them. The most control you get is to wait those 730-2,191 days and get an *exchange* in the person who then gets to control your money and your choices. Voting in this system doesn't give you any control, it merely gives another person 1,000,000s of times as much control as everyone else. They are lawyers who won basically a popularity contest to gain control of $Trillions of our money. **\"\"Horrible\"\" corporation** - the only provider of a service, sets the prices they want. You want the service, there's no doubt about it, but you want to pay less and get better quality. They'd *love* to be able to force you to pay for their service even if you don't want it, but they cannot. Soon enough, because of the high profits of the corporation, a new competitor arises, such as Verizon, Time Warner, or Google fiber and prices start dropping and quality goes up. All companies wish they were governments, where they could just force people with guns and threats of imprisonment to make them pay for their bloated services. Notice how the closer a company appears like a monopoly, the more it resembles the largest monopoly? Compare how similar the long lines at Walmart resemble the long lines at the post office or DMV?\"",
"title": ""
},
{
"docid": "52532",
"text": "Hard to say in general. It depends on the actual numbers. First you need to check the suggested retail price of a new car, and the price that you can actually get it for. The difference between these prices is between non-existing and huge, depending on the car. Some dealers will sell you a car that has done 50 miles for a huge rebate - that means they can't sell their cars at full price but don't want to reduce the price. Used cars can be quite expensive compared to a new car or not, also depending on the brand. Estimate that a brand new car should drive 12 years and 200,000 miles without major repairs (go for a car with generous warranty or check reviews to make sure you are buying a long lasting car). Calculate the cost per year. Since you prefer driving a nicer new car, increase the cost for the first four years and reduce the cost for the last four years. With that information, check what the used car costs and if that is reasonable. Assuming 12 years life, a six your old car should be quite a bit less than 50% of a new one. You can improve your cost a bit: If your annual mileage is low, you might find a rather new car with huge mileage quite cheap which will still last many years. Or if your annual mileage is excessively high, you can look for a car that is a bit older with low mileage. Anyway, paying 70% of the price of a new passenger car for a used car that is six years old (you say <7 years, so I assume six years) seems excessive; it would mean the first user effectively paid 30% of the new price to drive the car for six years, and you pay 70% to drive another six years (estimated). You'd be much much better off buying a new car and selling it for 70% after six years.",
"title": ""
},
{
"docid": "47053",
"text": "\"If you really believe in the particular stocks, then don't worry about their daily price. Overall if the company is sound, and presumably paying a dividend, then you're in it for the long haul. Notwithstanding that, it is reasonable to look for a way out. The two you describe are quite different in their specifics. Selling sounds like the simpler of the two, but the trigger event, and if it is automatic or \"\"manual\"\" matters. If you are happy to put in a sell order at some time in the future, then just go ahead with that. Many brokers can place a STOP order, that will trigger on a certain price threshold being hit. Do note, however, that by default this would place a market order, and depending on the price that breaks through, in the event of a flash crash, depending on how fast the brokers systems were, you could find yourself selling quite cheaply. A STOP LIMIT order will place a limit order at a triggered price. This would limit your overall downside loss, but you might not sell at all if the market is really running away. Options are another reasonable way to deal with the situation, sort of like insurance. In this case you would likely buy a PUT, which would give you the right, but not the obligation to sell the stock at the price the that was specified in the option. In this case, no matter what, you are out the price of the option itself (hence my allusion to insurance), but if the event never happens then that was the price you paid to have that peace of mind. I cannot recommend a specific course of action, but hopefully that fleshed out the options you have.\"",
"title": ""
}
] |
480
|
Gpr124 suppresses BBB breakdown in mouse models of ischemic stroke.
|
[
{
"docid": "6325527",
"text": "Although blood–brain barrier (BBB) compromise is central to the etiology of diverse central nervous system (CNS) disorders, endothelial receptor proteins that control BBB function are poorly defined. The endothelial G-protein-coupled receptor (GPCR) Gpr124 has been reported to be required for normal forebrain angiogenesis and BBB function in mouse embryos, but the role of this receptor in adult animals is unknown. Here Gpr124 conditional knockout (CKO) in the endothelia of adult mice did not affect homeostatic BBB integrity, but resulted in BBB disruption and microvascular hemorrhage in mouse models of both ischemic stroke and glioblastoma, accompanied by reduced cerebrovascular canonical Wnt–β-catenin signaling. Constitutive activation of Wnt–β-catenin signaling fully corrected the BBB disruption and hemorrhage defects of Gpr124-CKO mice, with rescue of the endothelial gene tight junction, pericyte coverage and extracellular-matrix deficits. We thus identify Gpr124 as an endothelial GPCR specifically required for endothelial Wnt signaling and BBB integrity under pathological conditions in adult mice. This finding implicates Gpr124 as a potential therapeutic target for human CNS disorders characterized by BBB disruption.",
"title": "Gpr124 is essential for blood–brain barrier integrity in central nervous system disease"
}
] |
[
{
"docid": "3761017",
"text": "BACKGROUND Metformin, a widely used hypoglycemic drug, reduces stroke incidence and alleviates chronic inflammation in clinical trials. However, the effect of metformin in ischemic stroke is unclear. Here, we investigated the effect of metformin on ischemic stroke in mice and further explored the possible underlying mechanisms. METHODS Ninety-eight adult male CD-1 mice underwent 90-minute transient middle cerebral artery occlusion (tMCAO). Metformin (200 mg/kg) was administrated for up to 14 days. Neurobehavioral outcomes, brain infarct volume, inflammatory factors, blood-brain barrier (BBB) permeability and AMPK signaling pathways were evaluated following tMCAO. Oxygen glucose deprivation was performed on bEND.3 cells to explore the mechanisms of metformin in inhibiting inflammatory signaling pathways. RESULTS Infarct volume was reduced in metformin-treated mice compared to the control group following tMCAO (P < 0.05). Neurobehavioral outcomes were greatly improved in metformin-treated mice (P < 0.05). MPO+ cells, Gr1+ cells, MPO activity and BBB permeability were decreased after metformin administration (P < 0.05). In addition, metformin activated AMPK phosphorylation, inhibited NF-κB activation, down-regulated cytokine (IL-1β, IL-6, TNF-α) and ICAM-1 expression following tMCAO (P < 0.05). Furthermore, metformin activated AMPK signaling pathway and alleviated oxygen-glucose deprivation-induced ICAM-1 expression in bEND.3 cells (P < 0.05). Compound C, a selective AMPK inhibitor, eliminated this promotional effect. CONCLUSIONS Metformin down-regulated ICAM-1 in an AMPK-dependent manner, which could effectively prevent ischemia-induced brain injury by alleviating neutrophil infiltration, suggesting that metformin is a promising therapeutic agent in stroke therapy.",
"title": "Metformin attenuates blood-brain barrier disruption in mice following middle cerebral artery occlusion"
},
{
"docid": "23627419",
"text": "RATIONALE Although obstructive sleep apnea is associated with physiological perturbations that increase risk of hypertension and are proatherogenic, it is uncertain whether sleep apnea is associated with increased stroke risk in the general population. OBJECTIVES To quantify the incidence of ischemic stroke with sleep apnea in a community-based sample of men and women across a wide range of sleep apnea. METHODS Baseline polysomnography was performed between 1995 and 1998 in a longitudinal cohort study. The primary exposure was the obstructive apnea-hypopnea index (OAHI) and outcome was incident ischemic stroke. MEASUREMENTS AND MAIN RESULTS A total of 5,422 participants without a history of stroke at the baseline examination and untreated for sleep apnea were followed for a median of 8.7 years. One hundred ninety-three ischemic strokes were observed. In covariate-adjusted Cox proportional hazard models, a significant positive association between ischemic stroke and OAHI was observed in men (P value for linear trend: P = 0.016). Men in the highest OAHI quartile (>19) had an adjusted hazard ratio of 2.86 (95% confidence interval, 1.1-7.4). In the mild to moderate range (OAHI, 5-25), each one-unit increase in OAHI in men was estimated to increase stroke risk by 6% (95% confidence interval, 2-10%). In women, stroke was not significantly associated with OAHI quartiles, but increased risk was observed at an OAHI greater than 25. CONCLUSIONS The strong adjusted association between ischemic stroke and OAHI in community-dwelling men with mild to moderate sleep apnea suggests that this is an appropriate target for future stroke prevention trials.",
"title": "Obstructive sleep apnea-hypopnea and incident stroke: the sleep heart health study."
},
{
"docid": "18256197",
"text": "BACKGROUND AND PURPOSE The level of total homocysteine (tHcy) that confers a risk of ischemic stroke is unsettled, and no prospective cohort studies have included sufficient elderly minority subjects. We investigated the association between mild to moderate fasting tHcy level and the incidence of ischemic stroke, myocardial infarction, and vascular death in a multiethnic prospective study. METHODS A population-based cohort was followed for vascular events (stroke, myocardial infarction, and vascular death). Baseline values of tHcy and methylmalonic acid were measured among 2939 subjects (mean age, 69+/-10; 61% women, 53% Hispanics, 24% blacks, and 20% whites). Cox proportional models were used to calculate hazard ratios (HRs) and 95% CIs in tHcy categories after adjusting for age, race, education, renal insufficiency, B12 deficiency, and other risk factors. RESULTS The adjusted HR for a tHcy level > or =15 micromol/L compared with <10 micromol/L was greatest for vascular death (HR=6.04; 95% CI, 3.44 to 10.60), followed by combined vascular events (HR=2.27; 95% CI, 1.51 to 3.43), ischemic stroke (HR=2.01; 95% CI, 1.00 to 4.05), and nonvascular death (HR=2.02; 95% CI, 1.31 to 3.14). Mild to moderate elevations of tHcy of 10 to 15 micromol/L were not significantly predictive of ischemic stroke, but increased the risk of vascular death (2.27; 95% CI, 1.44 to 3.60) and combined vascular events (1.42; 95% CI, 1.06 to 1.88). The effect of tHcy was stronger among whites and Hispanics, but not a significant risk factor for blacks. CONCLUSIONS Total Hcy elevations above 15 micromol/L are an independent risk factor for ischemic stroke, whereas mild elevations of tHcy of 10 to 15 micromol/L are less predictive. The vascular effects of tHcy are greatest among whites and Hispanics, and less among blacks.",
"title": "Homocysteine and the risk of ischemic stroke in a triethnic cohort: the NOrthern MAnhattan Study."
},
{
"docid": "37065914",
"text": "BACKGROUND AND PURPOSE Soluble corin was decreased in coronary heart disease. Given the connections between cardiac dysfunction and stroke, circulating corin might be a candidate marker of stroke risk. However, the association between circulating corin and stroke has not yet been studied in humans. Here, we aimed to examine the association in patients wtith stroke and community-based healthy controls. METHODS Four hundred eighty-one patients with ischemic stroke, 116 patients with hemorrhagic stroke, and 2498 healthy controls were studied. Serum soluble corin and some conventional risk factors of stroke were examined. Because circulating corin was reported to be varied between men and women, the association between serum soluble corin and stroke was evaluated in men and women, respectively. RESULTS Patients with ischemic and hemorrhagic stroke had a significantly lower level of serum soluble corin than healthy controls in men and women (all P values, <0.05). In multivariate analysis, men in the lowest quartile of serum soluble corin were more likely to have ischemic (odds ratio [OR], 4.90; 95% confidence interval, 2.99-8.03) and hemorrhagic (OR, 17.57; 95% confidence interval, 4.85-63.71) stroke than men in the highest quartile. Women in the lowest quartile of serum soluble corin were also more likely to have ischemic (OR, 3.10; 95% confidence interval, 1.76-5.44) and hemorrhagic (OR, 8.54; 95% confidence interval, 2.35-31.02) stroke than women in the highest quartile. ORs of ischemic and hemorrhagic stroke were significantly increased with the decreasing levels of serum soluble corin in men and women (all P values for trend, <0.001). CONCLUSIONS Serum soluble corin was decreased in patients with stroke compared with healthy controls. Our findings raise the possibility that serum soluble corin may have a pathogenic role in stroke.",
"title": "Serum Soluble Corin is Decreased in Stroke."
},
{
"docid": "33884866",
"text": "OBJECTIVE The sphingosine-1-phosphate (S1P) receptor agonist fingolimod (FTY720), that has shown efficacy in advanced multiple sclerosis clinical trials, decreases reperfusion injury in heart, liver, and kidney. We therefore tested the therapeutic effects of fingolimod in several rodent models of focal cerebral ischemia. To assess the translational significance of these findings, we asked whether fingolimod improved long-term behavioral outcomes, whether delayed treatment was still effective, and whether neuroprotection can be obtained in a second species. METHODS We used rodent models of middle cerebral artery occlusion and cell-culture models of neurotoxicity and inflammation to examine the therapeutic potential and mechanisms of neuroprotection by fingolimod. RESULTS In a transient mouse model, fingolimod reduced infarct size, neurological deficit, edema, and the number of dying cells in the core and periinfarct area. Neuroprotection was accompanied by decreased inflammation, as fingolimod-treated mice had fewer activated neutrophils, microglia/macrophages, and intercellular adhesion molecule-1 (ICAM-1)-positive blood vessels. Fingolimod-treated mice showed a smaller infarct and performed better in behavioral tests up to 15 days after ischemia. Reduced infarct was observed in a permanent model even when mice were treated 4 hours after ischemic onset. Fingolimod also decreased infarct size in a rat model of focal ischemia. Fingolimod did not protect primary neurons against glutamate excitotoxicity or hydrogen peroxide, but decreased ICAM-1 expression in brain endothelial cells stimulated by tumor necrosis factor alpha. INTERPRETATION These findings suggest that anti-inflammatory mechanisms, and possibly vasculoprotection, rather than direct effects on neurons, underlie the beneficial effects of fingolimod after stroke. S1P receptors are a highly promising target in stroke treatment.",
"title": "Fingolimod provides long-term protection in rodent models of cerebral ischemia."
},
{
"docid": "16760369",
"text": "CONTEXT Clinicians and trialists have difficulty with identifying which patients are highest risk for cardiovascular events. Prior ischemic events, polyvascular disease, and diabetes mellitus have all been identified as predictors of ischemic events, but their comparative contributions to future risk remain unclear. OBJECTIVE To categorize the risk of cardiovascular events in stable outpatients with various initial manifestations of atherothrombosis using simple clinical descriptors. DESIGN, SETTING, AND PATIENTS Outpatients with coronary artery disease, cerebrovascular disease, or peripheral arterial disease or with multiple risk factors for atherothrombosis were enrolled in the global Reduction of Atherothrombosis for Continued Health (REACH) Registry and were followed up for as long as 4 years. Patients from 3647 centers in 29 countries were enrolled between 2003 and 2004 and followed up until 2008. Final database lock was in April 2009. MAIN OUTCOME MEASURES Rates of cardiovascular death, myocardial infarction, and stroke. RESULTS A total of 45,227 patients with baseline data were included in this 4-year analysis. During the follow-up period, a total of 5481 patients experienced at least 1 event, including 2315 with cardiovascular death, 1228 with myocardial infarction, 1898 with stroke, and 40 with both a myocardial infarction and stroke on the same day. Among patients with atherothrombosis, those with a prior history of ischemic events at baseline (n = 21,890) had the highest rate of subsequent ischemic events (18.3%; 95% confidence interval [CI], 17.4%-19.1%); patients with stable coronary, cerebrovascular, or peripheral artery disease (n = 15,264) had a lower risk (12.2%; 95% CI, 11.4%-12.9%); and patients without established atherothrombosis but with risk factors only (n = 8073) had the lowest risk (9.1%; 95% CI, 8.3%-9.9%) (P < .001 for all comparisons). In addition, in multivariable modeling, the presence of diabetes (hazard ratio [HR], 1.44; 95% CI, 1.36-1.53; P < .001), an ischemic event in the previous year (HR, 1.71; 95% CI, 1.57-1.85; P < .001), and polyvascular disease (HR, 1.99; 95% CI, 1.78-2.24; P < .001) each were associated with a significantly higher risk of the primary end point. CONCLUSION Clinical descriptors can assist clinicians in identifying high-risk patients within the broad range of risk for outpatients with atherothrombosis.",
"title": "Comparative determinants of 4-year cardiovascular event rates in stable outpatients at risk of or with atherothrombosis."
},
{
"docid": "32328114",
"text": "Stroke ranks as the third leading cause of death in the United States. It is now estimated that there are more than 700 000 incident strokes annually and 4.4 million stroke survivors.1 2 The economic burden of stroke was estimated by the American Heart Association to be $51 billion (direct and indirect costs) in 1999.3 Despite the advent of treatment of selected patients with acute ischemic stroke with tissue plasminogen activator and the promise of other experimental therapies, the best approach to reducing the burden of stroke remains prevention.4 5 High-risk or stroke-prone individuals can be identified and targeted for specific interventions.6 This is important because epidemiological data suggest a substantial leveling off of prior declines in stroke-related mortality and a possible increase in stroke incidence.7 8 The Stroke Council of the American Heart Association formed an ad hoc writing group to provide a clear and concise overview of the evidence regarding various established and potential stroke risk factors. The writing group was chosen based on expertise in specific subject areas, and it used literature review, reference to previously published guidelines, and expert opinion to summarize existing evidence and formulate recommendations (Table 1⇓). View this table: Table 1. Levels of Evidence and Grading of Recommendations As given in Tables 2 through 4⇓⇓⇓, risk factors or risk markers for a first stroke were classified according to potential for modification (nonmodifiable, modifiable, or potentially modifiable) and strength of evidence (well documented, less well documented).5 The tables give the estimated prevalence, population attributable risk, relative risk, and risk reduction with treatment for each factor when known. Population attributable risk reflects the proportion of ischemic strokes in the population that can be attributed to a particular risk factor and is given by the formula 100×[prevalence(relative risk−1)/prevalence(relative risk−1)+1]). …",
"title": "Primary prevention of ischemic stroke: A statement for healthcare professionals from the Stroke Council of the American Heart Association."
},
{
"docid": "27602752",
"text": "Encephalitis and dementia associated with acquired immunodeficiency syndrome (AIDS) are characterized by leukocyte infiltration into the CNS, microglia activation, aberrant chemokine expression, blood-brain barrier (BBB) disruption, and eventual loss of neurons. Little is known about whether human immunodeficiency virus 1 (HIV-1) infection of leukocytes affects their ability to transmigrate in response to chemokines and to alter BBB integrity. We now demonstrate that HIV infection of human leukocytes results in their increased transmigration across our tissue culture model of the human BBB in response to the chemokine CCL2, as well as in disruption of the BBB, as evidenced by enhanced permeability, reduction of tight junction proteins, and expression of matrix metalloproteinases (MMP)-2 and MMP-9. HIV-infected cells added to our model did not transmigrate in the absence of CCL2, nor did this condition alter BBB integrity. The chemokines CXCL10/interferon-gamma-inducible protein of 10 kDa, CCL3/macrophage inflammatory protein-1alpha, or CCL5/RANTES (regulated on activation normal T-cell expressed and secreted) did not enhance HIV-infected leukocyte transmigration or BBB permeability. The increased capacity of HIV-infected leukocytes to transmigrate in response to CCL2 correlated with their increased expression of CCR2, the chemokine receptor for CCL2. These data suggest that CCL2, but not other chemokines, plays a key role in infiltration of HIV-infected leukocytes into the CNS and the subsequent pathology characteristic of NeuroAIDS.",
"title": "CCL2/monocyte chemoattractant protein-1 mediates enhanced transmigration of human immunodeficiency virus (HIV)-infected leukocytes across the blood-brain barrier: a potential mechanism of HIV-CNS invasion and NeuroAIDS."
},
{
"docid": "21571708",
"text": "CONTEXT Circulating concentration of lipoprotein(a) (Lp[a]), a large glycoprotein attached to a low-density lipoprotein-like particle, may be associated with risk of coronary heart disease (CHD) and stroke. OBJECTIVE To assess the relationship of Lp(a) concentration with risk of major vascular and nonvascular outcomes. STUDY SELECTION Long-term prospective studies that recorded Lp(a) concentration and subsequent major vascular morbidity and/or cause-specific mortality published between January 1970 and March 2009 were identified through electronic searches of MEDLINE and other databases, manual searches of reference lists, and discussion with collaborators. DATA EXTRACTION Individual records were provided for each of 126,634 participants in 36 prospective studies. During 1.3 million person-years of follow-up, 22,076 first-ever fatal or nonfatal vascular disease outcomes or nonvascular deaths were recorded, including 9336 CHD outcomes, 1903 ischemic strokes, 338 hemorrhagic strokes, 751 unclassified strokes, 1091 other vascular deaths, 8114 nonvascular deaths, and 242 deaths of unknown cause. Within-study regression analyses were adjusted for within-person variation and combined using meta-analysis. Analyses excluded participants with known preexisting CHD or stroke at baseline. DATA SYNTHESIS Lipoprotein(a) concentration was weakly correlated with several conventional vascular risk factors and it was highly consistent within individuals over several years. Associations of Lp(a) with CHD risk were broadly continuous in shape. In the 24 cohort studies, the rates of CHD in the top and bottom thirds of baseline Lp(a) distributions, respectively, were 5.6 (95% confidence interval [CI], 5.4-5.9) per 1000 person-years and 4.4 (95% CI, 4.2-4.6) per 1000 person-years. The risk ratio for CHD, adjusted for age and sex only, was 1.16 (95% CI, 1.11-1.22) per 3.5-fold higher usual Lp(a) concentration (ie, per 1 SD), and it was 1.13 (95% CI, 1.09-1.18) following further adjustment for lipids and other conventional risk factors. The corresponding adjusted risk ratios were 1.10 (95% CI, 1.02-1.18) for ischemic stroke, 1.01 (95% CI, 0.98-1.05) for the aggregate of nonvascular mortality, 1.00 (95% CI, 0.97-1.04) for cancer deaths, and 1.00 (95% CI, 0.95-1.06) for nonvascular deaths other than cancer. CONCLUSION Under a wide range of circumstances, there are continuous, independent, and modest associations of Lp(a) concentration with risk of CHD and stroke that appear exclusive to vascular outcomes.",
"title": "Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality."
},
{
"docid": "7157436",
"text": "In the adult brain, new neurons are continuously generated in the subventricular zone and dentate gyrus, but it is unknown whether these neurons can replace those lost following damage or disease. Here we show that stroke, caused by transient middle cerebral artery occlusion in adult rats, leads to a marked increase of cell proliferation in the subventricular zone. Stroke-generated new neurons, as well as neuroblasts probably already formed before the insult, migrate into the severely damaged area of the striatum, where they express markers of developing and mature, striatal medium-sized spiny neurons. Thus, stroke induces differentiation of new neurons into the phenotype of most of the neurons destroyed by the ischemic lesion. Here we show that the adult brain has the capacity for self-repair after insults causing extensive neuronal death. If the new neurons are functional and their formation can be stimulated, a novel therapeutic strategy might be developed for stroke in humans.",
"title": "Neuronal replacement from endogenous precursors in the adult brain after stroke"
},
{
"docid": "21181273",
"text": "Prostaglandin E2 (PGE2) can stimulate tumor progression by modulating several proneoplastic pathways, including proliferation, angiogenesis, cell migration, invasion, and apoptosis. Although steady-state tissue levels of PGE2 stem from relative rates of biosynthesis and breakdown, most reports examining PGE2 have focused solely on the cyclooxygenase-dependent formation of this bioactive lipid. Enzymatic degradation of PGE2 involves the NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH). The present study examined a range of normal tissues in the human and mouse and found high levels of 15-PGDH in the large intestine. By contrast, the expression of 15-PGDH is decreased in several colorectal carcinoma cell lines and in other human malignancies such as breast and lung carcinomas. Consistent with these findings, we observe diminished 15-Pgdh expression in ApcMin+/- mouse adenomas. Enzymatic activity of 15-PGDH correlates with expression levels and the genetic disruption of 15-Pgdh completely blocks production of the urinary PGE2 metabolite. Finally, 15-PGDH expression and activity are significantly down-regulated in human colorectal carcinomas relative to matched normal tissue. In summary, these results suggest a novel tumor suppressive role for 15-PGDH due to loss of expression during colorectal tumor progression.",
"title": "15-Hydroxyprostaglandin dehydrogenase is down-regulated in colorectal cancer."
},
{
"docid": "14753395",
"text": "Neural signalling within the central nervous system (CNS) requires a highly controlled microenvironment. Cells at three key interfaces form barriers between the blood and the CNS: the blood-brain barrier (BBB), blood-CSF barrier and the arachnoid barrier. The BBB at the level of brain microvessel endothelium is the major site of blood-CNS exchange. The structure and function of the BBB is summarised, the physical barrier formed by the endothelial tight junctions, and the transport barrier resulting from membrane transporters and vesicular mechanisms. The roles of associated cells are outlined, especially the endfeet of astrocytic glial cells, and pericytes and microglia. The embryonic development of the BBB, and changes in pathology are described. The BBB is subject to short and long-term regulation, which may be disturbed in pathology. Any programme for drug discovery or delivery, to target or avoid the CNS, needs to consider the special features of the BBB.",
"title": "Structure and function of the blood–brain barrier"
},
{
"docid": "23983289",
"text": "OBJECTIVES We sought to determine which ICD-9-CM codes in Medicare Part A data identify cardiovascular and stroke risk factors. DESIGN AND PARTICIPANTS This was a cross-sectional study comparing ICD-9-CM data to structured medical record review from 23,657 Medicare beneficiaries aged 20 to 105 years who had atrial fibrillation. MEASUREMENTS Quality improvement organizations used standardized abstraction instruments to determine the presence of 9 cardiovascular and stroke risk factors. Using the chart abstractions as the gold standard, we assessed the accuracy of ICD-9-CM codes to identify these risk factors. MAIN RESULTS ICD-9-CM codes for all risk factors had high specificity (>0.95) and low sensitivity (< or =0.76). The positive predictive values were greater than 0.95 for 5 common, chronic risk factors-coronary artery disease, stroke/transient ischemic attack, heart failure, diabetes, and hypertension. The sixth common risk factor, valvular heart disease, had a positive predictive value of 0.93. For all 6 common risk factors, negative predictive values ranged from 0.52 to 0.91. The rare risk factors-arterial peripheral embolus, intracranial hemorrhage, and deep venous thrombosis-had high negative predictive value (> or =0.98) but moderate positive predictive values (range, 0.54-0.77) in this population. CONCLUSIONS Using ICD-9-CM codes alone, heart failure, coronary artery disease, diabetes, hypertension, and stroke can be ruled in but not necessarily ruled out. Where feasible, review of additional data (eg, physician notes or imaging studies) should be used to confirm the diagnosis of valvular disease, arterial peripheral embolus, intracranial hemorrhage, and deep venous thrombosis.",
"title": "Accuracy of ICD-9-CM codes for identifying cardiovascular and stroke risk factors."
},
{
"docid": "37619697",
"text": "BACKGROUND Phenylpropanolamine is commonly found in appetite suppressants and cough or cold remedies. Case reports have linked the use of products containing phenylpropanolamine to hemorrhagic stroke, often after the first use of these products. To study the association, we designed a case-control study. METHODS Men and women 18 to 49 years of age were recruited from 43 U.S. hospitals. Eligibility criteria included the occurrence of a subarachnoid or intracerebral hemorrhage within 30 days before enrollment and the absence of a previously diagnosed brain lesion. Random-digit dialing identified two matched control subjects per patient. RESULTS There were 702 patients and 1376 control subjects. For women, the adjusted odds ratio was 16.58 (95 percent confidence interval, 1.51 to 182.21; P=0.02) for the association between the use of appetite suppressants containing phenylpropanolamine and the risk of a hemorrhagic stroke and 3.13 (95 percent confidence interval, 0.86 to 11.46; P=0.08) for the association with the first use of a product containing phenylpropanolamine. All first uses of phenylpropanolamine involved cough or cold remedies. For men and women combined, the adjusted odds ratio was 1.49 (95 percent confidence interval, 0.84 to 2.64; P=0.17) for the association between the use of a product containing phenylpropanolamine and the risk of a hemorrhagic stroke, 1.23 (95 percent confidence interval, 0.68 to 2.24; P=0.49) for the association with the use of cough or cold remedies that contained phenylpropanolamine, and 15.92 (95 percent confidence interval, 1.38 to 184.13; P=0.03) for the association with the use of appetite suppressants that contained phenylpropanolamine. An analysis in men showed no increased risk of a hemorrhagic stroke in association with the use of cough or cold remedies containing phenylpropanolamine. No men reported the use of appetite suppressants. CONCLUSIONS The results suggest that phenylpropanolamine in appetite suppressants, and possibly in cough and cold remedies, is an independent risk factor for hemorrhagic stroke in women.",
"title": "Phenylpropanolamine and the risk of hemorrhagic stroke."
},
{
"docid": "6158879",
"text": "BACKGROUND Patients with diabetes mellitus (DM) are at high risk for recurrent cardiovascular events after acute coronary syndromes, in part because of increased platelet reactivity. The Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial Infarction 38 (TRITON-TIMI 38) showed an overall reduction in ischemic events with more intensive antiplatelet therapy with prasugrel than with clopidogrel but with more bleeding. We compared prasugrel with clopidogrel among subjects with DM in TRITON-TIMI 38. METHODS AND RESULTS We classified 13 608 subjects on the basis of preexisting history of DM and further according to insulin use. Prespecified analyses of the primary (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) and key secondary end points, including net clinical benefit (death, nonfatal myocardial infarction, nonfatal stroke, and nonfatal TIMI major bleeding) were compared by use of the log-rank test. We found that 3146 subjects had a preexisting history of DM, including 776 receiving insulin. The primary end point was reduced significantly with prasugrel among subjects without DM (9.2% versus 10.6%; hazard ratio [HR], 0.86; P=0.02) and with DM (12.2% versus 17.0%; HR, 0.70; P<0.001, P(interaction)=0.09). A benefit for prasugrel was observed among DM subjects on insulin (14.3% versus 22.2%; HR, 0.63; P=0.009) and those not on insulin (11.5% versus 15.3%; HR, 0.74; P=0.009). Myocardial infarction was reduced with prasugrel by 18% among subjects without DM (7.2% versus 8.7%; HR, 0.82; P=0.006) and by 40% among subjects with DM (8.2% versus 13.2%; HR, 0.60; P<0.001, P(interaction)=0.02). Although TIMI major hemorrhage was increased among subjects without DM on prasugrel (1.6% versus 2.4%; HR, 1.43; P=0.02), the rates were similar among subjects with DM for clopidogrel and prasugrel (2.6% versus 2.5%; HR, 1.06; P=0.81, P(interaction)=0.29). Net clinical benefit with prasugrel was greater for subjects with DM (14.6% versus 19.2%; HR, 0.74; P=0.001) than for subjects without DM (11.5% versus 12.3%; HR, 0.92; P=0.16, P(interaction)=0.05). CONCLUSIONS Subjects with DM tended to have a greater reduction in ischemic events without an observed increase in TIMI major bleeding and therefore a greater net treatment benefit with prasugrel compared with clopidogrel. These data demonstrate that the more intensive oral antiplatelet therapy provided with prasugrel is of particular benefit to patients with DM.",
"title": "Greater clinical benefit of more intensive oral antiplatelet therapy with prasugrel in patients with diabetes mellitus in the trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with prasugrel-Thrombolysis in Myocardial Infarction 38."
},
{
"docid": "10766688",
"text": "Population diversity data have recently provided profound, albeit inferential, insights into meiotic recombination across the human genome, revealing a landscape dominated by thousands of cross-over hotspots. However, very few of these putative hotspots have been directly analyzed for cross-over activity. We now describe a search for very active hotspots, by using extreme breakdown of marker association as a guide for high-resolution sperm cross-over analysis. This strategy has led to the isolation of the most active cross-over hotspots yet described. Their morphology, sequence attributes, and cross-over processes are very similar to those seen at less active hotspots, but their activity in sperm is poorly predicted from population diversity information. Several of these hotspots showed evidence for biased gene conversion accompanying cross-over, in some cases associated with variation between men in cross-over activity and with two hotspots showing complete presence/absence polymorphism in different men. Hotspot polymorphism is very common at less active hotspots but curiously was not seen at any of the most active hotspots. This contrasts with the prediction that extreme hotspots should be the most vulnerable to attenuation by meiotic drive in favor of mutations that suppress recombination and should therefore show rapid rate evolution and thus variation in activity between men. Finally, these very intense hotspots provide a valuable resource for dissecting meiotic recombination processes and pathways in humans.",
"title": "Sperm cross-over activity in regions of the human genome showing extreme breakdown of marker association."
},
{
"docid": "2682997",
"text": "Despite the importance of CNS blood vessels, the molecular mechanisms that regulate CNS angiogenesis and blood-brain barrier (BBB) formation are largely unknown. Here we analyze the role of Wnt/beta-catenin signaling in regulating the formation of CNS blood vessels. First, through the analysis of TOP-Gal Wnt reporter mice, we identify that canonical Wnt/beta-catenin signaling is specifically activated in CNS, but not non-CNS, blood vessels during development. This activation correlates with the expression of different Wnt ligands by neural progenitor cells in distinct locations throughout the CNS, including Wnt7a and Wnt7b in ventral regions and Wnt1, Wnt3, Wnt3a, and Wnt4 in dorsal regions. Blockade of Wnt/beta-catenin signaling in vivo specifically disrupts CNS, but not non-CNS, angiogenesis. These defects include reduction in vessel number, loss of capillary beds, and the formation of hemorrhagic vascular malformations that remain adherent to the meninges. Furthermore, we demonstrate that Wnt/beta-catenin signaling regulates the expression of the BBB-specific glucose transporter glut-1. Taken together these experiments reveal an essential role for Wnt/beta-catenin signaling in driving CNS-specific angiogenesis and provide molecular evidence that angiogenesis and BBB formation are in part linked.",
"title": "Wnt/beta-catenin signaling is required for CNS, but not non-CNS, angiogenesis."
},
{
"docid": "118568",
"text": "INTRODUCTION Endothelial activation leading to vascular barrier breakdown plays an essential role in the pathophysiology of multiple-organ dysfunction syndrome (MODS) in sepsis. Increasing evidence suggests that the function of the vessel-protective factor Angiopoietin-1 (Ang-1), a ligand of the endothelial-specific Tie2 receptor, is inhibited by its antagonist Angiopoietin-2 (Ang-2) during sepsis. In order to reverse the effects of the sepsis-induced suppression of Ang-1 and elevation of Ang-2 we aimed to investigate whether an intravenous injection of recombinant human (rh) Ang-1 protects against MODS in murine sepsis. METHODS Polymicrobiological abdominal sepsis was induced by cecal ligation and puncture (CLP). Mice were treated with either 1 μg of intravenous rhAng-1 or control buffer immediately after CLP induction and every 8h thereafter. Sham-operated animals served as time-matched controls. RESULTS Compared to buffer-treated controls, rhAng-1 treated septic mice showed significant improvements in several hematologic and biochemical indicators of MODS. Moreover, rhAng-1 stabilized endothelial barrier function, as evidenced by inhibition of protein leakage from lung capillaries into the alveolar compartment. Histological analysis revealed that rhAng-1 treatment attenuated leukocyte infiltration in lungs and kidneys of septic mice, probably due to reduced endothelial adhesion molecule expression in rhAng-1 treated mice. Finally, the protective effects of rhAng-1 treatment were reflected by an improved survival time in a lethal CLP model. CONCLUSIONS In a clinically relevant murine sepsis model, intravenous rhAng-1 treatment alone is sufficient to significantly improve a variety of sepsis-associated organ dysfunctions and survival time, most likely by preserving endothelial barrier function. Further studies are needed to pave the road for clinical application of this therapy concept.",
"title": "Acute administration of recombinant Angiopoietin-1 ameliorates multiple-organ dysfunction syndrome and improves survival in murine sepsis."
},
{
"docid": "8227227",
"text": "The locations of cerebral infarctions were studied in 14 patients with tuberculous meningitis (TBM) and 173 patients with noninflammatory ischemic stroke (IS). In patients with TBM, 75% of infarctions occurred in the “TB zone” supplied by medial striate and thalamoperforating arteries; only 11% occurred in the “IS zone” supplied by lateral striate, anterior choroidal and thalamogeniculate arteries. In patients with IS 29% of infarctions occurred in the IS zone, 29% in the subcortical white matter, and 24% in (or involving) the cerebral cortex. Only 11% occurred in the TB zone. Bilaterally symmetrical infarctions of the TB zone were common with TMB (71%) but rare with IS (5%).",
"title": "Locations of cerebral infarctions in tuberculous meningitis"
},
{
"docid": "5884524",
"text": "BACKGROUND Although unstable coronary artery disease is the most common reason for admission to a coronary care unit, the long-term prognosis of patients with this diagnosis is unknown. This is particularly true for patients with diabetes mellitus, who are known to have a high morbidity and mortality after an acute myocardial infarction. METHODS AND RESULTS Prospectively collected data from 6 different countries in the Organization to Assess Strategies for Ischemic Syndromes (OASIS) registry were analyzed to determine the 2-year prognosis of diabetic and nondiabetic patients who were hospitalized with unstable angina or non-Q-wave myocardial infarction. Overall, 1718 of 8013 registry patients (21%) had diabetes. Diabetic patients had a higher rate of coronary bypass surgery than nondiabetic patients (23% versus 20%, P:<0.001) but had similar rates of catheterization and angioplasty. Diabetes independently predicted mortality (relative risk [RR], 1.57; 95% CI, 1.38 to 1.81; P:<0.001), as well as cardiovascular death, new myocardial infarction, stroke, and new congestive heart failure. Moreover, compared with their nondiabetic counterparts, women had a significantly higher risk than men (RR, 1.98; 95% CI, 1.60 to 2.44; and RR, 1.28; 95% CI, 1.06 to 1.56, respectively). Interestingly, diabetic patients without prior cardiovascular disease had the same event rates for all outcomes as nondiabetic patients with previous vascular disease. CONCLUSIONS Hospitalization for unstable angina or non-Q-wave myocardial infarction predicts a high 2-year morbidity and mortality; this is especially evident for patients with diabetes. Diabetic patients with no previous cardiovascular disease have the same long-term morbidity and mortality as nondiabetic patients with established cardiovascular disease after hospitalization for unstable coronary artery disease.",
"title": "Impact of diabetes on long-term prognosis in patients with unstable angina and non-Q-wave myocardial infarction: results of the OASIS (Organization to Assess Strategies for Ischemic Syndromes) Registry."
},
{
"docid": "12561083",
"text": "BACKGROUND Several studies have demonstrated that women with nonobstructive coronary disease have a high rate of subsequent investigations, rehospitalizations for recurrent chest pain, and repeat coronary angiography. The sex specificity of this finding is unclear. We therefore undertook an evaluation of sex differences in rehospitalization for acute coronary syndrome (ACS) or chest pain in patients with \"angiographically normal\" coronaries. METHODS A retrospective cohort study using prospectively collected angiographic and clinical data on all patients in British Columbia, Canada, presenting for their first cardiac catheterization with suspected ischemic heart disease but angiographically normal coronaries. RESULTS Among 32,856 patients, 7.1% of men versus 23.3% of women were angiographically normal (P < .001). Among angiographically normal patients, women were older and more likely to present with hypertension, prior stroke, chronic obstructive pulmonary disease, and peripheral vascular disease than men, but Canadian Cardiovascular Society class of angina did not vary by sex. Within 1 year, 1.0% died, (19 women, 18 men, P = .27) and 0.6% had a stroke (13 women, 9 men, P = .91). Readmission to hospital for ACS or chest pain requiring catheterization was significantly higher in women compared to men (adjusted OR 4.06; 95% CI 1.15-14.31). CONCLUSIONS In a contemporary, population-based cohort presenting for cardiac catheterization for suspected ischemia, women with angiographically normal coronaries were >4 times more likely to be readmitted to hospital for ACS/chest pain within 180 days compared to men. The observed sex difference has important social and economic implications and suggests that traditional diagnostic methods may not be optimal for women.",
"title": "Angina with \"normal\" coronary arteries: sex differences in outcomes."
},
{
"docid": "23785605",
"text": "BACKGROUND Migraine, particularly with aura, is a risk factor for early-onset ischemic stroke. The underlying mechanisms are unknown, but may in part be due to migraineurs having an increased risk profile for cardiovascular disease. In this study, the authors compare the cardiovascular risk profile of adult migraineurs to that of nonmigraineurs. METHODS Participants (n = 5,755, 48% men, age 20 to 65 years) are from the Genetic Epidemiology of Migraine (GEM) study, a population-based study in the Netherlands. A total of 620 current migraineurs were identified: 31% with aura (MA), 64% without aura (MO), and 5% unclassified. Controls were 5,135 individuals without lifetime migraine. Measured cardiovascular risk factors included blood pressure (BP), serum total and high-density lipoprotein cholesterol (TC, HDL), smoking, oral contraceptive use, and the Framingham risk score for myocardial infarction or coronary heart disease (CHD) death. RESULTS Compared to controls, migraineurs were more likely to smoke (OR = 1.43 [1.1 to 1.8]), less likely to consume alcohol (OR = 0.58 [0.5 to 0.7]), and more likely to report a parental history of early myocardial infarction. Migraineurs with aura were more likely to have an unfavorable cholesterol profile (TC > or = 240 mg/dL [OR = 1.43 (0.97 to 2.1)], TC:HDL ratio > 5.0 [OR = 1.64 (1.1 to 2.4)]), have elevated BP (systolic BP > 140 mm Hg or diastolic BP > 90 mm Hg [OR = 1.76 (1.04 to 3.0)]), and report a history of early onset CHD or stroke (OR = 3.96 [1.1 to 14.3]); female migraineurs with aura were more likely to be using oral contraceptives (OR = 2.06 [1.05 to 4.0]). The odds of having an elevated Framingham risk score for CHD were approximately doubled for the migraineurs with aura. CONCLUSIONS Migraineurs, particularly with aura, have a higher cardiovascular risk profile than individuals without migraine.",
"title": "Cardiovascular risk factors and migraine: the GEM population-based study."
},
{
"docid": "14848619",
"text": "Hypoxia is a common cause of cell death and is implicated in many disease processes including stroke and chronic degenerative disorders. In response to hypoxia, cells express a variety of genes, which allow adaptation to altered metabolic demands, decreased oxygen demands, and the removal of irreversibly damaged cells. Using polymerase chain reaction–based suppression subtractive hybridization to find genes that are differentially expressed in hypoxia, we identified the BH3-only Bcl-2 family protein Noxa. Noxa is a candidate molecule mediating p53-induced apoptosis. We show that Noxa promoter responds directly to hypoxia via hypoxia-inducible factor (HIF)-1α. Suppression of Noxa expression by antisense oligonucleotides rescued cells from hypoxia-induced cell death and decreased infarction volumes in an animal model of ischemia. Further, we show that reactive oxygen species and resultant cytochrome c release participate in Noxa-mediated hypoxic cell death. Altogether, our results show that Noxa is induced by HIF-1α and mediates hypoxic cell death.",
"title": "BH3-only Protein Noxa Is a Mediator of Hypoxic Cell Death Induced by Hypoxia-inducible Factor 1α"
},
{
"docid": "33669399",
"text": "Gametophytic self-incompatibility (SI) in plants is a widespread mechanism preventing self-fertilization and the ensuing inbreeding depression, but it often evolves to self-compatibility. We analyze genetic mechanisms for the breakdown of gametophytic SI, incorporating a dynamic model for the evolution of inbreeding depression allowing for partial purging of nearly recessive lethal mutations by selfing, and accounting for pollen limitation and sheltered load linked to the S-locus. We consider two mechanisms for the breakdown of gametophytic SI: a nonfunctional S-allele and an unlinked modifier locus that inactivates the S-locus. We show that, under a wide range of conditions, self-compatible alleles can invade a self-incompatible population. Conditions for invasion are always less stringent for a nonfunctional S-allele than for a modifier locus. The spread of self-compatible genotypes is favored by extremely high or low selfing rates, a small number of S-alleles, and pollen limitation. Observed parameter values suggest that the maintenance of gametophytic SI is caused by a combination of high inbreeding depression in self-incompatible populations coupled with intermediate selfing rates of the self-compatible genotypes and sheltered load linked to the S-locus.",
"title": "Loss of gametophytic self-incompatibility with evolution of inbreeding depression."
},
{
"docid": "9122283",
"text": "RATIONALE Multiple biological mechanisms contribute to the efficacy of cardiac cell therapy. Most prominent among these are direct heart muscle and blood vessel regeneration from transplanted cells, as opposed to paracrine enhancement of tissue preservation and/or recruitment of endogenous repair. OBJECTIVE Human cardiac progenitor cells, cultured as cardiospheres (CSps) or as CSp-derived cells (CDCs), have been shown to be capable of direct cardiac regeneration in vivo. Here we characterized paracrine effects in CDC transplantation and investigated their relative importance versus direct differentiation of surviving transplanted cells. METHODS AND RESULTS In vitro, many growth factors were found in media conditioned by human adult CSps and CDCs; CDC-conditioned media exerted antiapoptotic effects on neonatal rat ventricular myocytes, and proangiogenic effects on human umbilical vein endothelial cells. In vivo, human CDCs secreted vascular endothelial growth factor, hepatocyte growth factor, and insulin-like growth factor 1 when transplanted into the same SCID mouse model of acute myocardial infarction where they were previously shown to improve function and to produce tissue regeneration. Injection of CDCs in the peri-infarct zone increased the expression of Akt, decreased apoptotic rate and caspase 3 level, and increased capillary density, indicating overall higher tissue resilience. Based on the number of human-specific cells relative to overall increases in capillary density and myocardial viability, direct differentiation quantitatively accounted for 20% to 50% of the observed effects. CONCLUSIONS Together with their spontaneous commitment to cardiac and angiogenic differentiation, transplanted CDCs serve as \"role models,\" recruiting endogenous regeneration and improving tissue resistance to ischemic stress. The contribution of the role model effect rivals or exceeds that of direct regeneration.",
"title": "Relative roles of direct regeneration versus paracrine effects of human cardiosphere-derived cells transplanted into infarcted mice."
},
{
"docid": "5254463",
"text": "Colorectal cancer is one of the major causes of cancer-related deaths. To gain further insights into the mechanisms underlying its development, we investigated the role of Wip1 phosphatase, which is highly expressed in intestinal stem cells, in the mouse model of APC(Min)-driven polyposis. We found that Wip1 removal increased the life span of APC(Min) mice through a significant suppression of polyp formation. This protection was dependent on the p53 tumor suppressor, which plays a putative role in the regulation of apoptosis of intestinal stem cells. Activation of apoptosis in stem cells of Wip1-deficient mice, but not wild-type APC(Min) mice, increased when the Wnt pathway was constitutively activated. We propose, therefore, that the Wip1 phosphatase regulates homeostasis of intestinal stem cells. In turn, Wip1 loss suppresses APC(Min)-driven polyposis by lowering the threshold for p53-dependent apoptosis of stem cells, thus preventing their conversion into tumor-initiating stem cells.",
"title": "Wip1 phosphatase regulates p53-dependent apoptosis of stem cells and tumorigenesis in the mouse intestine."
},
{
"docid": "20544428",
"text": "Recent studies have highlighted the involvement of the peripheral immune system in delayed cellular degeneration after stroke. In the permanent middle cerebral artery occlusion (MCAO) model of stroke, the spleen decreases in size. This reduction occurs through the release of splenic immune cells. Systemic treatment with human umbilical cord blood cells (HUCBC) 24 h post-stroke blocks the reduction in spleen size while significantly reducing infarct volume. Splenectomy 2 weeks prior to MCAO also reduces infarct volume, further demonstrating the detrimental role of this organ in stroke-induced neurodegeneration. Activation of the sympathetic nervous system after MCAO results in elevated catecholamine levels both at the level of the spleen, through direct splenic innervation, and throughout the systemic circulation upon release from the adrenal medulla. These catecholamines bind to splenic alpha and beta adrenoreceptors. This study examines whether catecholamines regulate the splenic response to stroke. Male Sprague-Dawley rats either underwent splenic denervation 2 weeks prior to MCAO or received injections of carvedilol, a pan adrenergic receptor blocker, prazosin, an alpha1 receptor blocker, or propranolol, a beta receptor blocker. Denervation was confirmed by reduced splenic expression of tyrosine hydroxylase. Denervation prior to MCAO did not alter infarct volume or spleen size. Propranolol treatment also had no effects on these outcomes. Treatment with either prazosin or carvedilol prevented the reduction in spleen size, yet only carvedilol significantly reduced infarct volume (p < 0.05). These results demonstrate that circulating blood borne catecholamines regulate the splenic response to stroke through the activation of both alpha and beta adrenergic receptors.",
"title": "Blockade of adrenoreceptors inhibits the splenic response to stroke."
},
{
"docid": "13235609",
"text": "Inhibition of VEGF signaling leads to a proinvasive phenotype in mouse models of glioblastoma multiforme (GBM) and in a subset of GBM patients treated with bevacizumab. Here, we demonstrate that vascular endothelial growth factor (VEGF) directly and negatively regulates tumor cell invasion through enhanced recruitment of the protein tyrosine phosphatase 1B (PTP1B) to a MET/VEGFR2 heterocomplex, thereby suppressing HGF-dependent MET phosphorylation and tumor cell migration. Consequently, VEGF blockade restores and increases MET activity in GBM cells in a hypoxia-independent manner, while inducing a program reminiscent of epithelial-to-mesenchymal transition highlighted by a T-cadherin to N-cadherin switch and enhanced mesenchymal features. Inhibition of MET in GBM mouse models blocks mesenchymal transition and invasion provoked by VEGF ablation, resulting in substantial survival benefit.",
"title": "VEGF inhibits tumor cell invasion and mesenchymal transition through a MET/VEGFR2 complex."
},
{
"docid": "14834714",
"text": "In recent years, the treatment of autoimmune diseases has been significantly advanced by the use of biological agents. However, some biologics are accompanied with severe side effects, including tuberculosis and other types of infection. There is thus a critical need for nonsystemic and lesion-specific methods of delivering these therapeutic agents. We attempted to treat a mouse model of arthritis by using T cells that expressed a regulatory molecule and were specifically directed to the inflamed paw. To this end, we first identified the TCR alphabeta genes accumulating in the inflamed paw of mice with collagen-induced arthritis (CIA) by a combination of single-strand chain polymorphism analysis of TCR and single-cell sorting. We identified an expanded clone B47 which is autoreactive but is not specific to type II collagen. In vivo, TCR genes from B47-transduced T cells accumulated in the inflamed paw. Injection of cells cotransduced with the B47 and soluble TNFRIg genes resulted in a significant suppression of CIA. The suppression was correlated with the amount of TNFRIg transcripts in the hind paw, not with the serum concentrations of TNFRIg. Moreover, T cells cotransduced with the B47 and intracellular Foxp3 genes significantly suppressed CIA with reductions in TNF-alpha, IL-17A, and IL-1beta expression and bone destruction. T cells cotransduced with B47 and Foxp3 genes also suppressed the progression of established CIA. Therefore, immunosuppressive therapy with autoreactive TCR is a promising therapeutic strategy for arthritis whether the TCRs are used to deliver either soluble or intracellular suppressive molecules.",
"title": "Gene therapy of arthritis with TCR isolated from the inflamed paw."
},
{
"docid": "38355793",
"text": "OBJECTIVE A20 is a TNF-inducible primary response gene, which has been found to have antiapoptotic function in several cancer cells. This study investigates A20 expression in human glioma tissues and four glioma cell lines, and its effect on tumorigenesis of glioma cells and a mouse tumor model. METHODS Human glioma tissue samples and cells were subject to reverse transcription-PCR (RT-PCR), western blotting and immunohistochemistry. Glioma cells was tested by flow cytometry. A xenograft tumor model in mice was utilized to examine the knock-down effect of specific A20 siRNAs on tumorigenesis. RESULTS A20 was overexpressed in clinical glioma tissue samples (63.9%) and correlated with clinical staging. All four human glioma cell lines expressed A20, among which U87 displayed the strongest expression signals. Inhibiting A20 expression by siRNAs in vitro reduced the growth rates of glioma cells and resulted in G1/S arrest and increased apoptosis. In a mouse tumor model, local administration of siRNA significantly suppressed solid tumor growth. CONCLUSIONS A20 was overexpressed both in human glioma tissues and cell lines, and inhibiting A20 expression greatly slowed tumor cell growth in culture and in mice. These findings indicated that A20 is involved in tumorigenesis of human glioma, and may serve as a future therapeutic target.",
"title": "A20 is overexpressed in glioma cells and may serve as a potential therapeutic target."
}
] |
5a84e4dc5542994c784dda7d
|
What company produced both Bambi and Nikki, Wild Dog of the North?
|
[
{
"docid": "683122",
"text": "Bambi is a 1942 American animated film directed by David Hand (supervising a team of sequence directors), produced by Walt Disney and based on the book \"Bambi, a Life in the Woods\" by Austrian author Felix Salten. The film was released by RKO Radio Pictures on August 13, 1942, and is the fifth Disney animated feature film.",
"title": ""
},
{
"docid": "31716175",
"text": "Nikki, Wild Dog of the North is the title character and a 1961 Walt Disney film directed by Jack Couffer and Don Haldane.",
"title": ""
}
] |
[
{
"docid": "47576334",
"text": "Is Your Dog A Genius is a three-part American interactive documentary television series airing on Nat Geo Wild. The series, hosted by Dr. Brian Hare, uses a series of tests known as 'The Dognition Assessment' to determine what skills a dog possesses to determine how intelligent your dogs are. The series is produced by Authentic Entertainment.",
"title": ""
},
{
"docid": "47207479",
"text": "The Chadian wild dog (\"Lycaon pictus sharicus\") also known as Shari River hunting dog, Saharan wild dog or Central African wild dog is a subspecies of African wild dog native to Central Africa.",
"title": ""
},
{
"docid": "5705466",
"text": "The Fairbanks Ice Dogs are a Tier II Junior A ice hockey team in the North American Hockey League's Midwest Division. The Ice Dogs play home games at the 2,200-seat Big Dipper Ice Arena in Fairbanks, Alaska. The Ice Dogs are well known for their rivalry with the Wenatchee Wild when the Wild were in the NAHL.",
"title": ""
},
{
"docid": "2769164",
"text": "Frederick Brewing Company (at one point also known as Wild Goose Brewery) is a brewery at the Wedgewood Business Park in Frederick, Maryland, United States. It was founded sometime between 1992 and 1993 by Marjorie McGinnis, Kevin Brannon, and Steve Nordahl and had its grand opening on 12 February 1997. The company was taken over by Snyder International Brewing Group in 1999 and merged with Snyder International Brewing Group in 2001. In early 2002 or 2003 the company was placed into receivership and in 2006 was purchased by Flying Dog Brewery and renamed Wild Goose Brewery. At some point the brewery stopped being known as Wild Goose Brewery and just became Flying Dog Brewery.",
"title": ""
},
{
"docid": "8237962",
"text": "Gustaf Adolf Tenggren (November 3, 1896 – April 9, 1970) was a Swedish-American illustrator. He is known for his Arthur Rackham-influenced fairy-tale style and use of silhouetted figures with caricatured faces. Tenggren was a chief illustrator for The Walt Disney Company in the late 1930s, in what has been called the Golden Age of American animation, when animated feature films such as \"Snow White and the Seven Dwarfs\", \"Fantasia\", \"Bambi\" and \"Pinocchio\" were produced.",
"title": ""
},
{
"docid": "44308521",
"text": "The Cape wild dog (\"Lycaon pictus pictus\"), also known as South African wild dog or Cape hunting dog, is the nominate subspecies of African wild dog native to Southern Africa.",
"title": ""
},
{
"docid": "18000949",
"text": "The Wenatchee Wild is a Junior A ice hockey team in the British Columbia Hockey League. The team plays its home games at the 4,300-seat Town Toyota Center in Wenatchee, Washington. Initially, the team was part of the North American Hockey League, joining as an expansion club for the 2008–09 season, and in that time they were well known for their rivalry with the Fairbanks Ice Dogs. The Wild moved to the BCHL for 2015–16, after seeking approval from both Hockey Canada and USA Hockey for three years.",
"title": ""
},
{
"docid": "14431510",
"text": "The Adjule, also known as Kelb-el-khela, is a canine cryptid, claimed to inhabit the North African region, especially the areas in and around Sahara Desert in Mauritania. Reported primarily by the nomadic Tuaregs, and Théodore Monod in 1928, the adjule is said to be a totally unknown canine which takes the form of a dog or wolf, but today is described as isolated population of African wild dog. Some alternative names are \"kelb el khela\" (\"bush dog\") for the male and \"tarhsît\" for the female. However, despite a continuing firm belief in its existence due to urban myths, this cryptid has since been debunked and its sightings attributed to wild canines mistaken for the adjule, such as the African wild dog which is now extinct in certain areas of the Sahara. There is one unconfirmed sighting of a canid-like animal from the coastal area of Mauritania in 1992; hunters living in the coastal areas of the Western Sahara, to the north of Mauritania, described an animal resembling a wild dog, which hunted in packs. However, this was not confirmed for \"Lycaon pictus\" species (IUCN/CSG, 1997).",
"title": ""
},
{
"docid": "45306577",
"text": "The Wild Dogs Act, initially passed in 1912, was a piece of South Australian legislation regarding wild dogs and dingos in Australia, and subtitled \"An Act to provide for the Destruction of Wild Dogs\". This act led to an economy of dingo scalping to collect bounties.",
"title": ""
},
{
"docid": "49055936",
"text": "The West African wild dog (\"Lycaon pictus manguensis\") is a subspecies of African wild dog native to West Africa. It is classified as Critically Endangered by IUCN, as it was estimated that 70 adult individuals are left in the wild.",
"title": ""
},
{
"docid": "13356064",
"text": "Wild Dog Diaries is a wild life film portraying the behaviour of wild dogs (\"Cuon alpinus\"). The film was directed by the photographer duo of Krupakar-Senani and mainly filmed in the Bandipur National Park and the Mudumalai National Park of India.",
"title": ""
},
{
"docid": "47935342",
"text": "The Wild Dog Destruction Board is an agency of the New South Wales Government established in 1921, under the \"Wild Dog Destruction Act 1921\"",
"title": ""
},
{
"docid": "39461078",
"text": "Bamby Cars was a British built marque of microcars produced in small numbers in Hull, England, in the early 1980s. Bambys were designed and built by Alan Evans, who manufactured a one-off replica of the Peel P50 which also served as a prototype for further production.",
"title": ""
},
{
"docid": "44302269",
"text": "The Somali wild dog (\"Lycaon pictus somalicus\") is a subspecies of African wild dog native to the Horn of Africa. It is similar to the East African wild dog, but is smaller, has shorter and coarser fur, and has a weaker dentition. Its colour closely approaches that of the Cape form, with the yellow parts being buff rather than bright orange as is the case in the East African subspecies.",
"title": ""
},
{
"docid": "3164511",
"text": "The Bambi, often simply called Bambi Awards and stylised as BAMBI, are presented annually by Hubert Burda Media to recognize excellence in international media and television, awarded to personalities in the media, arts, culture, sports and other fields \"with vision and creativity who affected and inspired the German public that year,\" both domestic and foreign. First held in 1948, they are the oldest media awards in Germany. The award is named after Felix Salten's book \"Bambi, A Life in the Woods\" and its statuettes are in the shape of the novel's titular fawn character. They were originally made of porcelain, until 1958 when the organizers switched to using gold, with the casting done by the art casting workshop of Ernst Strassacker in Süßen.",
"title": ""
},
{
"docid": "17021807",
"text": "Rare breed (dog) is any breed of dog that is small in number and is used to refer to both old established breeds such as the Stabyhoun and Glen of Imaal Terrier or newer creations. Since dogs have greater genetic variability than other domesticated animals the number of possible breeds is vast with new crosses constantly occurring, from these both selected and random crosses may come new breeds should offspring reliably breed true to type. New breeds from the wild such as the Carolina Dog are quite rare compared to attempts at breed creation from man as found in the American Hairless Terrier which sought to exploit a mutation.",
"title": ""
},
{
"docid": "2432192",
"text": "The Wild House was a serialised children's programme produced between 1997 and 1999 broadcast by the BBC. The idea was created by Jean Buchanan, and later series were written partially by Mark Haddon, author of \"The Curious Incident of the Dog in the Night-time\". It follows the life of Natalie Wild (played by Ellie Beaven) and the other members of the Wild family.",
"title": ""
},
{
"docid": "4211609",
"text": "Happidog is a producer of vegetarian dog foods. First produced in 1980, Happidog is widely considered to be the first dog food produced with vegetarianism in mind. Based in Norwich, England, the company manufactures dog food using various grains, primarily wheat, barley, rice, and soy, with no animal products, no artificial preservatives, and no artificial colourings. It is BUAV certified for not using animal testing and can be shipped from the United Kingdom almost anywhere in the world. Vegetarian pop stars Paul McCartney and Howard Jones have both bought Happidog. This health food was once available in tins, which dogs found even more appetizing. This could be due to its softer consistency as the ingredients were hydrated for much longer than the dry version usually is. There was also Happipup, designed for puppies. In the nineties the company produced a vegan version alongside the regular product, which used the more expensive vitamin D2 instead of vitamin D3. Also in that decade, Happidog Crunchy Nuggets were introduced. In 2009 Happidog changed its name to V-Dog. Also the added vitamin D is now from a non-animal source making the product vegan friendly and thus completely cruelty-free",
"title": ""
},
{
"docid": "49136771",
"text": "The Lure of the Wild is a 1925 silent film dramatic thriller directed by Frank R. Strayer and starring Alan Roscoe, Jane Novak and Lightning the Dog. It was produced and released by Columbia Pictures.",
"title": ""
},
{
"docid": "5057635",
"text": "Bambi a.d. (Serbian Cyrillic: Бамби а.д.) is a food manufacturing company in Požarevac, Serbia. One of its signature products is biscuit called \"Plazma\".",
"title": ""
},
{
"docid": "8626",
"text": "The dhole /dəʊl/ (\"Cuon alpinus\") is a canid native to Central, South and Southeast Asia. Other English names for the species include Asiatic wild dog, Indian wild dog, whistling dog, red dog, and mountain wolf. It is genetically close to species within the genus \"Canis\", though its skull is convex rather than concave in profile, it lacks a third lower molar and the upper molars sport only a single cusp as opposed to two to four. During the Pleistocene, the dhole ranged throughout Asia, Europe and North America but became restricted to its historical range 12,000–18,000 years ago.",
"title": ""
},
{
"docid": "44308193",
"text": "The East African wild dog (\"Lycaon pictus lupinus\") is a subspecies of African wild dog native to East Africa. It is distinguished from the nominate Cape form by its smaller size and much blacker coat.",
"title": ""
},
{
"docid": "4015208",
"text": "Who Killed Bambi? was to be the first film featuring the punk rock band the Sex Pistols, and was due to be released in 1978. Russ Meyer and then Jonathan Kaplan were due to direct from a script by Roger Ebert and Pistols' manager Malcolm McLaren. The film was intended as a punk rock version of \"A Hard Day's Night\". Ebert asserted that only a day and a half's worth of shooting took place, although this is contradicted by Julian Bray, who supplied location services to McLaren's Matrixbest company. The filming was halted when 20th Century Fox, who were shocked by what they read in the script, pulled all funding. Sets that had been built at Bray Studios in Berkshire were destroyed.",
"title": ""
},
{
"docid": "27588760",
"text": "The G. M. Standifer Construction Company was an American company that built three shipyards on the Columbia River for the World War I effort, one in Oregon and two in Washington. After the war it maintained its original yard in north Portland, Oregon. The north Portland yard, and one of the Vancouver, Washington yards (located where the Red Lion at the Quay is today, just west of the Interstate Bridge) produced wooden ships. The other Vancouver yard, located just west of what was then the Spokane, Portland and Seattle Railway bridge (now the BNSF bridge) produced steel-hulled ships. The Portland yard was located about a mile to the west, just downstream from the BNSF bridge. Both Vancouver yards were closed in 1921.",
"title": ""
},
{
"docid": "9020070",
"text": "The African Wild Dog Conservancy (AWD Conservancy) is a non-profit, 501(c)(3), non-governmental organization, working with local communities, and national and international stakeholders, to conserve the African wild dog through scientific research and education.",
"title": ""
},
{
"docid": "30441791",
"text": "The Natural Dog Food Company is the producer of the All in One range of holistic complete dog foods available primarily within the UK.",
"title": ""
},
{
"docid": "1550604",
"text": "Hunting For Bambi is a series of hoax videos publicized in the summer of 2003 that center on a fictional competition to hunt semi-naked women with paintball guns in the deserts of Las Vegas. Created by Florida resident Michael Burdick, \"Hunting For Bambi\" drew significant controversy and media coverage, due both to its perceived misogyny and to Burdick's repeated public statements that it was \"not\" a hoax (he later retracted these statements when faced with the possibility of prosecution).",
"title": ""
},
{
"docid": "28934119",
"text": "In machine learning and natural language processing, a topic model is a type of statistical model for discovering the abstract \"topics\" that occur in a collection of documents. Topic modeling is a frequently used text-mining tool for discovery of hidden semantic structures in a text body. Intuitively, given that a document is about a particular topic, one would expect particular words to appear in the document more or less frequently: \"dog\" and \"bone\" will appear more often in documents about dogs, \"cat\" and \"meow\" will appear in documents about cats, and \"the\" and \"is\" will appear equally in both. A document typically concerns multiple topics in different proportions; thus, in a document that is 10% about cats and 90% about dogs, there would probably be about 9 times more dog words than cat words. The \"topics\" produced by topic modeling techniques are clusters of similar words. A topic model captures this intuition in a mathematical framework, which allows examining a set of documents and discovering, based on the statistics of the words in each, what the topics might be and what each document's balance of topics is.",
"title": ""
},
{
"docid": "3277055",
"text": "Wild Dog is a fictional character, a vigilante and a superhero appearing in American comic books published by DC Comics. He first appeared in \"Wild Dog\" #1 (September 1987), and was created by Max Allan Collins and Terry Beatty. His original alter-ego was Jack Wheeler.",
"title": ""
},
{
"docid": "13011135",
"text": "Dog Eat Dog Films is film director Michael Moore's production company. Dog Eat Dog Films has produced films, television programs, and DVDs. Moore founded Dog Eat Dog Films in 1989.",
"title": ""
}
] |
PLAIN-2765
|
The Safety of Tarragon
|
[
{
"docid": "MED-4547",
"text": "Biogenic amines, produced by bacterial decarboxylation of amino acids, have been associated with toxicological symptoms in food products. Twenty-three samples of traditionally available Korean fermented soybean paste samples (Doenjang) were analyzed in order to determine the content of biogenic amines. Amines were extracted with 0.4M perchloric acid and derivatized with dansyl chloride. Nine biogenic amines were separated from Doenjang samples by high performance liquid chromatography using gradient elution (acetonitrile and ammonium acetate), and detected with spectrophotometric UV-vis detection at 254 nm. The pH value of all the samples was ranged from 4.8 to 6.0, and the strong amino acid decarboxylase activity was found to be in an acidic environment. The mean values of biogenic amines (tryptamine, 2-phenyl-ethylamine, putrescine, cadaverine, agmatine, histamine, tyramine, spermidine and spermine) determined in 23 Doenjang samples were found to be 18.37, 82.03, 70.84, 34.24, 47.32, 26.79, 126.66, 74.41 and 244.36 mg%, respectively. The findings of this study enhance the safety of not only Doenjang but other salted and/or fermented food products. Copyright (c) 2010 Elsevier Ltd. All rights reserved.",
"title": "Determination of biogenic amines in Korean traditional fermented soybean paste (Doenjang)."
},
{
"docid": "MED-3812",
"text": "AIMS: Various spices display insulin-potentiating activity in vitro, and in particular, cinnamon spice and its phenolic extracts have been shown to exhibit these capabilities. In vivo study shows that cinnamon may have beneficial effects on glucose homeostasis; therefore the aim of this study was to further investigate this phenomenon in humans. METHODS: Seven lean healthy male volunteers, aged 26 +/- 1 years, body mass index 24.5 +/- 0.3 kg/m(2) (mean +/- s.e.m.), underwent three oral glucose tolerance tests (OGTT) supplemented with either a 5 g placebo (OGTT(control)), 5 g of cinnamon (OGTT(cin)), or 5 g of cinnamon taken 12 h before (OGTT(cin12hpre)) in a randomized-crossover design. RESULTS: Cinnamon ingestion reduced total plasma glucose responses (AUC) to oral glucose ingestion [-13% and -10% for OGTT(cin) (p < 0.05) and OGTT(cin12hpre) (p < 0.05), respectively], as well as improving insulin sensitivity as assessed by insulin sensitivity index measures based on Matsuda's model in both OGTT(cin) (p < 0.05) and OGTT(cin12hpre) (p < 0.05) trials compared with OGTT(control). CONCLUSIONS: These data illustrate that cinnamon spice supplementation may be important to in vivo glycaemic control and insulin sensitivity in humans, and not only are its effects immediate, they also appear to be sustained for 12 h.",
"title": "Effects of short-term cinnamon ingestion on in vivo glucose tolerance."
},
{
"docid": "MED-5116",
"text": "BACKGROUND: Laboratory research and a growing number of epidemiologic studies have provided evidence for a reduced risk of breast cancer associated with dietary intake of certain classes of flavonoids. However, the effects of flavonoids on survival are not known. In a population-based cohort of breast cancer patients, we investigated whether dietary flavonoid intake before diagnosis is associated with subsequent survival. METHODS: Women ages 25 to 98 years who were newly diagnosed with a first primary invasive breast cancer between August 1, 1996, and July 31, 1997, and participated in a population-based, case-control study (n=1,210) were followed for vital status through December 31, 2002. At the case-control interview conducted shortly after diagnosis, respondents completed a FFQ that assessed dietary intake in the previous 12 months. All-cause mortality (n=173 deaths) and breast cancer-specific mortality (n=113 deaths) were determined through the National Death Index. RESULTS: Reduced hazard ratios [age- and energy-adjusted hazard ratio (95% confidence interval)] for all-cause mortality were observed among premenopausal and postmenopausal women for the highest quintile of intake, compared with the lowest, for flavones [0.63 (0.41-0.96)], isoflavones [0.52 (0.33-0.82)], and anthocyanidins [0.64 (0.42-0.98)]. No significant trends in risk were observed. Results were similar for breast cancer-specific mortality only. CONCLUSION: Mortality may be reduced in association with high levels of dietary flavones and isoflavones among postmenopausal U.S. breast cancer patients. Larger studies are needed to confirm our findings.",
"title": "Dietary flavonoid intake and breast cancer survival among women on Long Island."
},
{
"docid": "MED-4878",
"text": "Background Telomere length reflects biological aging and may be influenced by environmental factors, including those that affect inflammatory processes. Objective With data from 840 white, black, and Hispanic adults from the Multi-Ethnic Study of Atherosclerosis, we studied cross-sectional associations between telomere length and dietary patterns and foods and beverages that were associated with markers of inflammation. Design Leukocyte telomere length was measured by quantitative polymerase chain reaction. Length was calculated as the amount of telomeric DNA (T) divided by the amount of a single-copy control DNA (S) (T/S ratio). Intake of whole grains, fruit and vegetables, low-fat dairy, nuts or seeds, nonfried fish, coffee, refined grains, fried foods, red meat, processed meat, and sugar-sweetened soda were computed with responses to a 120-item food-frequency questionnaire completed at baseline. Scores on 2 previously defined empirical dietary patterns were also computed for each participant. Results After adjustment for age, other demographics, lifestyle factors, and intakes of other foods or beverages, only processed meat intake was associated with telomere length. For every 1 serving/d greater intake of processed meat, the T/S ratio was 0.07 smaller (β ± SE: −0.07 ± 0.03, P = 0.006). Categorical analysis showed that participants consuming ≥1 serving of processed meat each week had 0.017 smaller T/S ratios than did nonconsumers. Other foods or beverages and the 2 dietary patterns were not associated with telomere length. Conclusions Processed meat intake showed an expected inverse association with telomere length, but other diet features did not show their expected associations.",
"title": "Dietary patterns, food groups, and telomere length in the Multi-Ethnic Study of Atherosclerosis (MESA)"
},
{
"docid": "MED-4051",
"text": "The food mutagens IQ (2-amino-3-methylimidazo[4,5-f]quinoline) and PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) are heterocyclic amines (HCA), generated when heating proteinaceous food. This study investigates the protective potential of the flavonoids quercetin (Q) and rutin (R) against oxidative stress induced in vitro by IQ and PhIP in lymphocytes from healthy individuals and untreated, newly diagnosed colon cancer patients using the Comet assay. In the presence of up to 500μM Q and R, the DNA damage resulting from a high dose of PhIP (75μM) or IQ (150μM) was significantly reduced (P<0.001) to levels comparable to six times lower IQ or 7.5 times lower PhIP doses. Lymphocytes from colon cancer patients had greater baseline DNA damage than those from healthy individuals (P<0.01) and this higher level of damage was also observed throughout in vitro treatment. Except for the >50years of age group and male gender, confounding factors such as smoking, drinking and/or dietary habits were not found to be significant. In conclusion, flavonoids reduced oxidative stress caused by food mutagens in vitro in lymphocytes of healthy individuals and colon cancer patients. Thus, dietary supplementation with flavonoid-rich vegetables and fruits may prove very effective in protecting against oxidative stress. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "The protective effect of the flavonoids on food-mutagen-induced DNA damage in peripheral blood lymphocytes from colon cancer patients."
},
{
"docid": "MED-4389",
"text": "Significant benefits for diabetes prevention and management have been observed with vegetarian and especially vegan diets. This article reviews observational studies and intervention trials on such diets, and discusses their efficacy, nutritional adequacy, acceptability, and sustainability. Research to date has demonstrated that a low-fat, plant-based nutritional approach improves control of weight, glycemia, and cardiovascular risk. These studies have also shown that carefully planned vegan diets can be more nutritious than diets based on more conventional diet guidelines, with an acceptability that is comparable with that of other therapeutic regimens. Current intervention guidelines from professional organizations offer support for this approach. Vegetarian and vegan diets present potential advantages in managing type 2 diabetes that merit the attention of individuals with diabetes and their caregivers.",
"title": "Usefulness of vegetarian and vegan diets for treating type 2 diabetes."
},
{
"docid": "MED-4047",
"text": "The total phenolic contents and antioxidant activities of garlics from California, Oregon, Washington, and New York were determined by Fourier transform infrared (FT-IR) spectroscopy (400-4000 cm(-1)). The total phenolic content was quantified [Folin-Ciocalteu assay (FC)] and three antioxidant activity assays, 2,2-diphenyl-picrylhydrazyl (DPPH) assay, Trolox equivalent antioxidant capacity (TEAC) assay, and ferric reducing antioxidant power (FRAP), were employed for reference measurements. Four independent partial least-squares regression (PLSR) models were constructed with spectra from 25 extracts and their corresponding FC, DPPH, TEAC, and FRAP with values for 20 additional extracts predicted (R > 0.95). The standard errors of calibration and standard error of cross-validation were <1.45 (TEAC), 0.36 (FRAP), and 0.33 μmol Trolox/g FW (DPPH) and 0.55 mg gallic acid/g FW (FC). Cluster and dendrogram analyses could segregate garlic grown at different locations. Hydroxyl and phenolic functional groups most closely correlated with garlic antioxidant activity.",
"title": "Determination of total phenolic content and antioxidant activity of garlic (Allium sativum) and elephant garlic (Allium ampeloprasum) by attenuated..."
},
{
"docid": "MED-4877",
"text": "BACKGROUND: Telomeres are protective DNA-protein complexes at the end of linear chromosomes that promote chromosomal stability. Telomere shortness in human beings is emerging as a prognostic marker of disease risk, progression, and premature mortality in many types of cancer, including breast, prostate, colorectal, bladder, head and neck, lung, and renal cell. Telomere shortening is counteracted by the cellular enzyme telomerase. Lifestyle factors known to promote cancer and cardiovascular disease might also adversely affect telomerase function. However, previous studies have not addressed whether improvements in nutrition and lifestyle are associated with increases in telomerase activity. We aimed to assess whether 3 months of intensive lifestyle changes increased telomerase activity in peripheral blood mononuclear cells (PBMC). METHODS: 30 men with biopsy-diagnosed low-risk prostate cancer were asked to make comprehensive lifestyle changes. The primary endpoint was telomerase enzymatic activity per viable cell, measured at baseline and after 3 months. 24 patients had sufficient PBMCs needed for longitudinal analysis. This study is registered on the ClinicalTrials.gov website, number NCT00739791. FINDINGS: PBMC telomerase activity expressed as natural logarithms increased from 2.00 (SD 0.44) to 2.22 (SD 0.49; p=0.031). Raw values of telomerase increased from 8.05 (SD 3.50) standard arbitrary units to 10.38 (SD 6.01) standard arbitrary units. The increases in telomerase activity were significantly associated with decreases in low-density lipoprotein (LDL) cholesterol (r=-0.36, p=0.041) and decreases in psychological distress (r=-0.35, p=0.047). INTERPRETATION: Comprehensive lifestyle changes significantly increase telomerase activity and consequently telomere maintenance capacity in human immune-system cells. Given this finding and the pilot nature of this study, we report these increases in telomerase activity as a significant association rather than inferring causation. Larger randomised controlled trials are warranted to confirm the findings of this study.",
"title": "Increased telomerase activity and comprehensive lifestyle changes: a pilot study."
},
{
"docid": "MED-3806",
"text": "BACKGROUND: Unpleasant and frightening side effects associated with the abuse of nutmeg occasionally generate emergency department referrals. We report a young patient's first-time experience with nutmeg and review the mechanisms of its toxicity. CASE REPORT: A 13-year-old female ingested 15-24 g of nutmeg over a 3-hour period and smoked and shared 2 joints of marijuana. To facilitate ingestion, the nutmeg was put into 00-000 gelatin capsules. Bizarre behavior and visual, auditory, and tactile hallucinations developed. She also experienced nausea, gagging, hot/cold sensations, and blurred vision followed by numbness, double, and \"triple\" vision, headache, and drowsiness. Nystagmus, muscle weakness, and ataxia were present. Her vital signs and laboratory tests were normal. She received 50 g of activated charcoal and except for complaints of dizziness and visual changes, her 2-day admission was uneventful. The central nervous system activity of nutmeg is often postulated to result from biotransformation of its chemical components to amphetamine-like compounds, but this has not been proven. Nutmeg contains several compounds with structural similarities to substances with known central nervous system neuromodulatory activity.",
"title": "Toxicology of nutmeg abuse."
},
{
"docid": "MED-3807",
"text": "Artemisia dracunculus L. (tarragon) has a long history of use as a spice and remedy. Two well-described \"cultivars\" (Russian and French) are used widely and differ in ploidy level, morphology, and chemistry. Key biologically active secondary metabolites are essential oils (0.15-3.1%), coumarins (>1%), flavonoids, and phenolcarbonic acids. In vivo studies mainly in rodents, particularly from Russian sources, highlight potential anti-inflammatory, hepatoprotective, and antihyperglycemic effects. Despite concerns about the toxic effects of two of its main constituents, estragole (up to 82%) and methyleugenol (up to 39%), no acute toxicity or mutagenic activity has been reported at doses relevant for human consumption. Water extracts of A. dracunculus contain very low amounts of estragole and methyleugenol and, therefore, are considered to pose a very limited risk. Overall, a stronger focus on clinical studies and precise taxonomic and phytochemical definition of the source material will be essential for future research efforts.",
"title": "Artemisia dracunculus L. (tarragon): a critical review of its traditional use, chemical composition, pharmacology, and safety."
},
{
"docid": "MED-4546",
"text": "The acute and subacute toxicity of five biogenic amines-tyramine, spermidine, spermine, putrescine and cadaverine-were examined in Wistar rats. Tyramine and cadaverine had a low acute oral toxicity of more than 2000 mg/kg body weight. Putrescine had an acute oral toxicity of 2000 mg/kg body weight and spermidine and spermine each of 600 mg/kg body weight. All amines investigated caused a dose-related decrease in blood pressure after intravenous administration, except for tyramine, where an increase was found. In 6-wk studies the biogenic amines were administered in the diet to groups of 10 male and 10 female rats. Tyramine and cadaverine were given at levels of 0, 200, 2000 or 10,000 ppm, spermine and putrescine at levels of 0, 200, 2000 or 5000 ppm and spermidine at levels of 0, 20, 200 or 500/1000 ppm in the first study and at levels of 0 or 10,000 ppm in a second study. Spermine was the most toxic. The high dose level showed a great number of changes, such as emaciation, aggressiveness, convulsions and paralysis of the hind legs. Growth, food intake and water intake were considerably decreased. Slight anaemia (males) and changes in plasma clinical chemistry occurred. The relative weights of the thyroid, adrenals, spleen and heart were increased and that of the liver decreased. Impaired kidney function, together with renal histopathological changes and changes in plasma electrolytes and urea, occurred with spermine. Histopathological examinations also revealed decreased glycogen content in the liver, reduction of spermatogenesis, severe depletion of splenic white pulp, acute involution of the thymus and moderate myocardial degeneration in the heart. Myocardial degeneration was also seen in one mid-dose male. Adverse effects were also observed in the top dose groups of all other amines. Decreased body weights associated with diminished food intake were generally seen. Slight increases in packed cell volume, haemoglobin concentration and thrombocytes occurred with cadaverine. With spermidine, decreased plasma creatinine, calcium and inorganic phosphate were observed and decreased potassium levels with cadaverine. The no-observed-adverse-effect level was 2000 ppm (180 mg/kg body weight/day) for tyramine, cadaverine and putrescine, 1000 ppm (83 mg/kg body weight/day) for spermidine and 200 ppm (19 mg/kg body weight/day) for spermine.",
"title": "Acute and subacute toxicity of tyramine, spermidine, spermine, putrescine and cadaverine in rats."
},
{
"docid": "MED-3808",
"text": "Methylchavicol (or estragole), a natural flavouring substance present in tarragon, was confirmed as a genotoxic chemical in the in vitro UDS test in cultured rat hepatocytes and in the in vivo UDS test in hepatocytes of exposed rats. Deep-frozen tarragon was clearly less genotoxic than methylchavicol at equivalent dose levels, and desiccated tarragon was negative. Both forms of tarragon tested in vitro have the ability to decrease significantly the genotoxicity of methylchavicol added to the culture medium at concentrations </=10 muM for deep-frozen and </=55 muM for desiccated tarragon. The decrease may be attributed to antimutagenic properties of tarragon leaves and/or to adsorption of methylchavicol, which would decrease its bioavailability. Desiccated tarragon powder was not genotoxic in the in vivo UDS test when administered up to the maximum dose of 6.25 g/kg bw (18.75 mg/kg bw of methylchavicol). In vivo, desiccated tarragon did not show antimutagenic properties, because it did not decrease the genotoxicity of methylchavicol added at high concentrations. Considering the low exposure level at the maximum daily tarragon consumption, the rapid detoxification and excretion in humans and the no-genotoxic-effect-level of methylchavicol by the oral route when given to rats as tarragon leaves, a high margin of exposure exists. We can conclude that tarragon consumption presents no genotoxic risk to humans. Copyright © 2009 Elsevier B.V. All rights reserved.",
"title": "Risk assessment of consumption of methylchavicol and tarragon: the genotoxic potential in vivo and in vitro."
},
{
"docid": "MED-3810",
"text": "The typical spices used in winter include nutmeg, cinnamon, clove and anise. These spices contain two groups of chemicals, the allylbenzenes and their isomers, the propenylbenzenes. It was suggested 40 years ago by Alexander Shulgin that these substances act as metabolic precursors of amphetamines. The biotransformation of these precursors to nitrogen-containing metabolites is reviewed. These reactions have not been reported in humans. Whether or not the pharmacology and toxicology of spices such as nutmeg can be explained on the basis of their allylbenzene or propenylbenzene content is speculative. Humans may be exposed to amphetamines derived from these precursors in forno, the formation during baking and cooking, for example in the preparation of Lebkuchen, or Christmas gingerbread. It is possible that this may be responsible, in part, for uplifting our mood in winter. However, the role of these aromatic substances, acting simply as odours, evoking old memories of winters past, cannot be ignored. Whether spices have a true pharmacological effect or they act as aromatherapy remains to be elucidated through clinical and laboratory studies.",
"title": "Christmas gingerbread (Lebkuchen) and Christmas cheer--review of the potential role of mood elevating amphetamine-like compounds formed in vivo and..."
},
{
"docid": "MED-4375",
"text": "There is widespread concern over the presence of Hg in fish consumed by humans. While studies have been focused on determining the Hg concentration in sport fish and some commercial fish, little attention has been directed to canned tuna; it is widely held that concentrations are low. In the present study, the amount of Hg present in canned tuna purchased in Las Vegas, Nevada, USA, was examined, and the brand, temporal variation, type, and packaging medium impacts on Hg concentrations in tuna were explored. A significant (p < 0.001) brand difference was noted: Brand 3 contained higher Hg concentrations ($\\bar x$ standard deviation (SD) (0.777 +/- 0.320 ppm) than Brands 1 (0.541 +/- 0.114 ppm) and 2 (0.550 +/- 0.199 ppm). Chunk white tuna (0.619 +/- 0.212 ppm) and solid white tuna (0.576 +/- 0.178 ppm) were both significantly (p < 0.001) higher in mean Hg than chunk light tuna (0.137 +/- 0.063 ppm). No significant temporal variation was noted, and packaging had no significant effect on Hg concentration. In total, 55% of all tuna examined was above the U.S. Environmental Protection Agency's (U.S. EPA) safety level for human consumption (0.5 ppm), and 5% of the tuna exceeded the action level established by the U.S. Food and Drug Administration (U.S. FDA) (1.0 ppm). These results indicate that stricter regulation of the canned tuna industry is necessary to ensure the safety of sensitive populations such as pregnant women, infants, and children. According to the U.S. EPA reference dose of 0.1 microg/kg body weight per day and a mean Hg value of 0.619 ppm, a 25-kg child may consume a meal (75 g) of canned chunk white tuna only once every 18.6 d. Continued monitoring of the industry and efforts to reduce Hg concentrations in canned tuna are recommended. Environ. Copyright 2009 SETAC.",
"title": "An evaluation of mercury concentrations in three brands of canned tuna."
},
{
"docid": "MED-4618",
"text": "Persea americana is much sought after both for the nutritional value of its fruit and the medicinal values of its various plant parts. A chromosomal aberration assay was undertaken to evaluate the potential genotoxicity of crude extracts from avocado fruits and leaves. Chromosomal aberrations were observed in cultured human peripheral lymphocytes exposed to separately increasing concentrations of 50% methanolic extracts of Persea americana fruit and leaves. The groups exposed to leaf and fruit extracts, respectively, showed a concentration-dependent increase in chromosomal aberrations as compared to that in a control group. The mean percentage total aberrant metaphases at 100 mg/kg, 200 mg/kg, and 300 mg/kg concentrations of leaf extract were found respectively to be 58 ± 7.05, 72 ± 6.41, and 78 ± 5.98, which were significantly higher (p < 0.0001 each) than that in the control group (6 ± 3.39). The mean percentage total aberrant metaphases at 100 mg/kg, 200 mg/kg, and 300 mg/kg concentrations of fruit extract were found to be 18 ± 5.49, 40 ± 10.00, and 52 ± 10.20, respectively, which were significantly higher (p = 0.033, p < 0.0001, and p < 0.0001, respectively) than that for control (6 ± 3.39). Acrocentric associations and premature centromeric separation were the two most common abnormalities observed in both the exposed groups. The group exposed to leaf extracts also showed a significant number of a variety of other structural aberrations, including breaks, fragments, dicentrics, terminal deletion, minutes, and Robertsonian translocations. The group exposed to leaf extract showed higher frequency of all types of aberrations at equal concentrations as compared to the group exposed to fruit extract.",
"title": "In vitro evaluation of genotoxicity of avocado (Persea americana) fruit and leaf extracts in human peripheral lymphocytes."
},
{
"docid": "MED-861",
"text": "OBJECTIVE: To investigate the association of whole-blood fatty acids and reported intakes of fats with risk of prostate cancer (PCa). DESIGN: Case-control study of 209 men 40-80 years old with newly diagnosed, histologically confirmed prostate cancer and 226 cancer-free men attending the same urology clinics. Whole-blood fatty acid composition (mol%) was measured by gas chromatography and diet assessed by food frequency questionnaire. RESULTS: High whole-blood oleic acid composition (tertile 3 vs. tertile 1: OR, 0.37; CI, 0.14-0.0.98) and moderate palmitic acid proportions (tertile 2: OR, 0.29; CI, 0.12-0.70) (tertile 3: OR, 0.53; CI, 0.19-1.54) were inversely related to risk of PCa, whereas men with high linolenic acid proportions were at increased likelihood of PCa (tertile 3 vs. tertile 1: OR, 2.06; 1.29-3.27). Blood myristic, stearic and palmitoleic acids were not associated with PCa. Higher intakes of dietary MUFA were inversely related to prostate cancer (tertile 3 vs. tertile 1: OR, 0.39; CI 0.16-0.92). The principal source of dietary MUFA was avocado intake. Dietary intakes of other fats were not associated with PCa. CONCLUSIONS: Whole-blood and dietary MUFA reduced the risk of prostate cancer. The association may be related to avocado intakes. High blood linolenic acid was directly related to prostate cancer. These associations warrant further investigation.",
"title": "Associations of whole-blood fatty acids and dietary intakes with prostate cancer in Jamaica."
},
{
"docid": "MED-4946",
"text": "In order to assess early neurotoxic effects associated with relatively low levels of mercury absorbed through fish eating, two groups of 22 adult male subjects, habitual consumers of tuna fish, and 22 controls were examined using a cross-sectional field study. The assessment included neurobehavioral tests of vigilance and psychomotor function, hand tremor measurements and serum prolactin assessment. Mercury in urine (U-Hg) and serum prolactin (sPRL) were measured in all exposed subjects and controls, whereas measurements of the organic component of mercury in blood (O-Hg) were available for only 10 exposed and six controls. U-Hg was significant higher among exposed subjects (median 6.5 microg/g of creatinine, range 1.8-21.5) than controls (median 1.5 microg/g of creatinine, range 0.5-5.3). The median values of O-Hg were 41.5 microg/l among the tuna fish eaters and 2.6 microg/l in the control group. Both U-Hg and O-Hg were significantly correlated with the quantity of fish consumed per week. Significant differences in sPRL were found between exposed (12.6 ng/ml) and controls (9.1 ng/ml). Individual sPRL were significantly correlated with both U-Hg and O-Hg levels. The neurobehavioral performance of subjects who consumed tuna fish regularly was significantly worse on color word reaction time, digit symbol reaction time and finger tapping speed (FT). After considering the education level and other covariates, the multiple stepwise regression analysis indicated that O-Hg concentration was most significantly associated with individual performance on these tests, accounting for about 65% of the variance in test scores.",
"title": "Sub-clinical neurobehavioral abnormalities associated with low level of mercury exposure through fish consumption."
},
{
"docid": "MED-3811",
"text": "Cinnamon, the dry bark and twig of Cinnamomum spp., is a rich botanical source of polyphenolics that has been used for centuries in Chinese medicine and has been shown to affect blood glucose and insulin signaling. Cinnamon's effects on blood glucose have been the subject of many clinical and animal studies; however, the issue of cinnamon intake's effect on fasting blood glucose (FBG) in people with type 2 diabetes and/or prediabetes still remains unclear. A meta-analysis of clinical studies of the effect of cinnamon intake on people with type 2 diabetes and/or prediabetes that included three new clinical trials along with five trials used in previous meta-analyses was done to assess cinnamon's effectiveness in lowering FBG. The eight clinical studies were identified using a literature search (Pub Med and Biosis through May 2010) of randomized, placebo-controlled trials reporting data on cinnamon and/or cinnamon extract and FBG. Comprehensive Meta-Analysis (Biostat Inc., Englewood, NJ, USA) was performed on the identified data for both cinnamon and cinnamon extract intake using a random-effects model that determined the standardized mean difference ([i.e., Change 1(control) - Change 2(cinnamon)] divided by the pooled SD of the post scores). Cinnamon intake, either as whole cinnamon or as cinnamon extract, results in a statistically significant lowering in FBG (-0.49±0.2 mmol/L; n=8, P=.025) and intake of cinnamon extract only also lowered FBG (-0.48 mmol/L±0.17; n=5, P=.008). Thus cinnamon extract and/or cinnamon improves FBG in people with type 2 diabetes or prediabetes.",
"title": "Cinnamon intake lowers fasting blood glucose: meta-analysis."
},
{
"docid": "MED-3813",
"text": "Cinnamon can improve fasting glucose in humans yet data on insulin sensitivity are limited and controversial. Eight male volunteers (aged 25 +/- 1 years, body mass 76.5 +/- 3.0 kg, BMI 24.0 +/- 0.7 kg m(-2); mean +/- SEM) underwent two 14-day interventions involving cinnamon or placebo supplementation (3 g day(-1)). Placebo supplementation was continued for 5 days following this 14 day period. Oral glucose tolerance tests (OGTT) were performed on days 0, 1, 14, 16, 18, and 20. Cinnamon ingestion reduced the glucose response to OGTT on day 1 (-13.1 +/- 6.3% vs. day 0; P < 0.05) and day 14 (-5.5 +/- 8.1% vs. day 0; P = 0.09). Cinnamon ingestion also reduced insulin responses to OGTT on day 14 (-27.1 +/- 6.2% vs. day 0; P < 0.05), as well as improving insulin sensitivity on day 14 (vs. day 0; P < 0.05). These effects were lost following cessation of cinnamon feeding. Cinnamon may improve glycaemic control and insulin sensitivity, but the effects are quickly reversed.",
"title": "Changes in glucose tolerance and insulin sensitivity following 2 weeks of daily cinnamon ingestion in healthy humans."
},
{
"docid": "MED-4622",
"text": "We developed a probabilistic model to characterize the plausible distribution of health and economic benefits that would accrue to the U.S. population following reduction of methyl mercury (MeHg) exposure. MeHg, a known human developmental neurotoxicant, may increase fatal heart attack risks. Model parameters reflect current understanding of the relationships between MeHg intake, health risks, and societal valuation of these risks. The expected monetary value of the annual health benefits generated by a 10% reduction in U.S. population exposure to MeHg for one year is $860 million; 80% of this is associated with reductions in fatal heart attacks and the remainder with IQ gains. The plausible distribution of the benefits is quite broad with 5th and 95th percentile estimates of approximately $50 million and $3.5 billion, respectively. The largest source of uncertainty is whether epidemiological associations between MeHg exposure and fatal heart attacks reflect causality. The next largest sources of uncertainty concern the slope of the relationship between maternal MeHg exposure and reduced intelligence among children and whether this relationship exhibits a threshold. Our analysis suggests that the possible causal relationship between MeHg exposure and fatal heart attacks should be better characterized, using additional epidemiological studies and formally elicited expert judgment.",
"title": "A probabilistic characterization of the health benefits of reducing methyl mercury intake in the United States."
},
{
"docid": "MED-4053",
"text": "Heterocyclic amines (HCAs), potent mutagens and a risk factor for human cancers, are produced in meats cooked at high temperature. The aim of this study was to determine the HCA content in cooked meat products (beef, chicken, pork, fish) prepared by various cooking methods (pan frying, oven broiling, and oven baking at 170 to 230°C) that are preferred by U.S. meat consumers. The primary HCAs in these samples were PhIP (2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine) (1.49-10.89ng/g), MeIQx (2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline) (not detected-4.0ng/g), and DiMeIQx (2-amino-3,4,8-trimethyl-imidazo [4,5-f]quinoxaline) (not detected-3.57ng/g). Type and content of HCAs in cooked meat samples were highly dependent on cooking conditions. The total HCA content in well-done meat was 3.5 times higher than that of medium-rare meat. Fried pork (13.91ng/g) had higher levels of total HCAs than fried beef (8.92ng/g) and fried chicken (7.00ng/g). Among the samples, fried bacon contained the highest total HCA content (17.59ng/g). Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Occurrence of heterocyclic amines in cooked meat products."
},
{
"docid": "MED-3809",
"text": "Mutagenicity and liver toxicity of the herb tarragon (Artemisia dracunculus) were evaluated using single cell gel (comet) electrophoresis. Ten microlitres aliquots of peripheral venous human blood were incubated with tarragon extract, saline, or the mutagen sodium dichromate. Cell suspensions dispersed in low-melting agarose were electrophoresed in ethidium bromide. The resulting DNA migration trails were obtained using fluorescent microscopy at 400× magnification, and graded according to the mutagenicity index (MI) for each cell incubation condition. The in vivo liver toxicity of Artemisia dracunculus was assessed in the blood of mice treated orally with the extract of the herb, using alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as liver function indicators. Liver morphology was assessed using hematoxylin and eosin (HE) staining of liver tissue. The present study demonstrated a direct correlation between tarragon extract dosage and three major outcome variables: MI; serum liver enzyme activity; and liver histopathology. These outcomes are possibly due to the presence in tarragon of methylchavicol and other genotoxic compounds. These findings provide a preliminary guide for risk assessment of tarragon in diet and in possible therapeutic applications. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Toxicological and mutagenic analysis of Artemisia dracunculus (tarragon) extract."
},
{
"docid": "MED-4879",
"text": "To estimate age using DNA based on telomere shortening, we determined the terminal restriction fragment (TRF) length, as telomere length, using Southern blot analysis of peripheral human blood and blood stains. All blood stains had been stored at room temperature for 5 months. The average TRF length clearly showed a tendency to shortening with aging. The formula for age estimation was based on a correlation between average TRF length and age of the subjects. The estimated age calculated from TRF length widely depends on environmental and genetic factors. However, as long as the DNA is well preserved, use of our method is feasible regardless of age of the subject and can give a rough estimation of age of subjects in forensic samples that carry no morphological information. Copyright 2002 Elsevier Science Ireland Ltd.",
"title": "Estimating age of humans based on telomere shortening."
},
{
"docid": "MED-4055",
"text": "Heterocyclic amines (HCAs) are formed when meat products such as beef, chicken, pork and fish are cooked at high temperatures. The most abundant HCA found in the human diet is 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP). PhIP causes mammary carcinomas in female rats and mice, and is associated with an increased risk of developing colon, breast, and prostate cancer in humans. PhIP is metabolized by cytochrome P-450s producing N-OH-PhIP. The N-OH-PhIP can be esterified by phase II enzymes forming an arylnitrenium ion that binds to DNA causing adducts. Furthermore, N-OH-PhIP may be reduced by cytochrome b5 reductase producing superoxide anions and hydroxyl radicals causing DNA strand breaks. Diallyl sulfide (DAS) has been shown to prevent cancer in several animal models, presumably by metabolic modulation. We hypothesize that PhIP produces reactive oxygen species causing DNA strand breaks and that DAS will inhibit the formation of PhIP induced DNA strand breaks. To test this hypothesis we treated normal breast epithelial (MCF-10A) cells with PhIP, DAS and a combination of PhIP and DAS. The detection of lipid peroxides was used as a surrogate for ROS. Lipid peroxides were detected using a PeroxiDetect kit (Sigma). PhIP increased the production of lipid peroxides and DAS decreased the PhIP-induced peroxidation by 47%. To determine if PhIP causes DNA strand breaks in MCF-10A cells, cells were treated for 3, 6, 9, and 24 h with PhIP (100 microM), DAS (100 microM) and a combination of PhIP (100 microM) and DAS (100 microM). DNA strand breaks were evaluated using the Comet assay. PhIP produced DNA strand breaks in a dose- and time-dependent fashion. We have shown that DAS inhibits PhIP-induced DNA strand breaks by inhibiting the production of reactive oxygen species. Therefore, we propose that DAS can prevent PhIP-induced breast cancer.",
"title": "Diallyl sulfide inhibits PhIP-induced DNA strand breaks in normal human breast epithelial cells."
},
{
"docid": "MED-4049",
"text": "More than 85% of breast cancers are sporadic and attributable to long-term exposure to environmental carcinogens, such as those in the diet, through a multistep disease process progressing from non-cancerous to premalignant and malignant stages. The chemical carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is one of the most abundant heterocyclic amines found in high-temperature cooked meats and is recognized as a mammary carcinogen. However, the PhIP’s mechanism of action in breast cell carcinogenesis is not clear. Here, we demonstrated, for the first time, that cumulative exposures to PhIP at physiologically achievable, pico to nanomolar concentrations effectively induced progressive carcinogenesis of human breast epithelial MCF10A cells from a non-cancerous stage to premalignant and malignant stages in a dose- and exposure-dependent manner. Progressive carcinogenesis was measured by increasingly- acquired cancer-associated properties of reduced dependence on growth factors, anchorage-independent growth, acinar-conformational disruption, proliferation, migration, invasion, tumorigenicity with metastasis and increased stem-like cell populations. These biological changes were accompanied by biochemical and molecular changes, including upregulated H-Ras gene expression, extracellular signal-regulated kinase (ERK) pathway activation, Nox-1 expression, reactive oxygen species (ROS) elevation, increased HIF-1α, Sp1, tumor necrosis factor-α, matrix metalloproteinase (MMP)-2, MMP-9, aldehyde dehydrogenase activity and reduced E-cadherin. The Ras-ERK-Nox-ROS pathway played an important role in not only initiation but also maintenance of cellular carcinogenesis induced by PhIP. Using biological, biochemical and molecular changes as targeted endpoints, we identified that the green tea catechin components epicatechin-3-gallate and epigallocatechin-3-gallate, at non-cytotoxic doses, were capable of suppressing PhIP-induced cellular carcinogenesis and tumorigenicity.",
"title": "Intervention of human breast cell carcinogenesis chronically induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine"
},
{
"docid": "MED-3802",
"text": "Methylchavicol (CH(3)-CV), an important aromatic constituent of different plants like tarragon and basils, has been shown to be carcinogenic by a mechanism yet unclear, although it has been reported that carcinogenicity of CH(3)-CV in rodent might be linked to its metabolic conversion into a genotoxic electrophilic metabolite generated through a two steps bioactivation pathway catalyzed by cytochrome P450 enzymes and sulfotransferases. The induction of carcinogenesis by certain agents has been associated with the generation of oxidative stress. The aim of the present study was to determine whether pure methylchavicol applied on a human hepatoma cell line, HepG2, could promote oxidative stress and might alter the expression of procarcinogenic biomarkers such as the drug-metabolizing enzyme (CYP2E1), the inducible form of nitric oxide synthase (iNOS) and might induce the expression of Cu/Zn-superoxide dismutase (Cu/Zn-SOD) and Mn-SOD that control the redox equilibrium of the cells. CH(3)-CV was shown to cause a significant induction of oxidative stress, as revealed by luminol-dependent chemiluminescence (LDCL) and to alter dramatically the expression of CYP2E1, iNOS and Mn-SOD, indicating that the toxic effect of CH(3)-CV could be mediated through a nitric oxide dependent mechanism. Under similar experimental conditions, the extracts from tarragon, chervil and basil did not induce such biological changes. These results provide evidence that the generation of an oxidative stress may be a significant event occurring during CH(3)-CV-induced toxicity. It also suggests that natural extracts containing different amounts of CH(3)-CV (tarragon, chervil and basil) did not elicit such toxicity and might contain compounds able to counteract this detrimental property. Copyright © 2012. Published by Elsevier Masson SAS.",
"title": "Fresh aromatic herbs containing methylchavicol did not exhibit the pro-oxidative effects of pure methylchavicol on a human hepatoma cell line, HepG2."
}
] |
[
{
"docid": "MED-3391",
"text": "Aim: To review special safety topics associated with sildenafil and to document the tolerability of 50- and 100-mg doses, overall and by age, in men with erectile dysfunction (ED). Methods: Data were collated from 67 double-blind placebo-controlled (DBPC) trials (> 14,000 men) conducted by the manufacturer and from the manufacturer’s postmarketing safety database (39,277 patients). The DBPC data were stratified by dose, starting dose and age (≥ 65 and ≥ 75 years). Special safety topics included cardiovascular risk, priapism, non-arteritic anterior ischaemic optic neuropathy (NAION), impaired renal and hepatic function, drug interactions (i.e. nitrates, cytochrome P3A4 inhibitors, other ED therapies and α-blockers) and incorrect use. Results: Sildenafil was well tolerated at a dose of 50 or 100 mg in men with ED, overall, in those aged ≥ 65 years, and in those aged ≥ 75 years. Analyses of the databases did not reveal any causal link between sildenafil and cardiovascular events, or any new safety risks relating to cardiovascular events, priapism, NAION, hearing loss or drug interactions. In the small number of men with moderate impairment of renal function or hepatic function who were treated with sildenafil in DBPC trials, the safety profile was similar to that in men with no impairment of renal or hepatic function. Overdose with sildenafil was rare in the ED population. No new safety issues, emerging trends or adverse reactions were identified in conjunction with overdose, dependence, abuse or misuse. Conclusion: This collated review confirms generally the good tolerability and established safety profile of sildenafil 50 and 100 mg in men with ED and reveals no new safety issues.",
"title": "Safety of sildenafil citrate: review of 67 double-blind placebo-controlled trials and the postmarketing safety database"
},
{
"docid": "MED-1451",
"text": "OBJECTIVE: To test the hypothesis that comprehensive efforts to reduce a workforce's health and safety risks can be associated with a company's stock market performance. METHODS: Stock market performance of Corporate Health Achievement Award winners was tracked under four different scenarios using simulation and past market performance. RESULTS: A portfolio of companies recognized as award winning for their approach to the health and safety of their workforce outperformed the market. Evidence seems to support that building cultures of health and safety provides a competitive advantage in the marketplace. This research may have also identified an association between companies that focus on health and safety and companies that manage other aspects of their business equally well. CONCLUSIONS: Companies that build a culture of health by focusing on the well-being and safety of their workforce yield greater value for their investors.",
"title": "The link between workforce health and safety and the health of the bottom line: tracking market performance of companies that nurture a \"culture of..."
},
{
"docid": "MED-1144",
"text": "Public risk perceptions and demand for safer food are important factors shaping agricultural production practices in the United States. Despite documented food safety concerns, little attempt has been made to elicit consumers' subjective risk judgments for a range of food safety hazards or to identify factors most predictive of perceived food safety risks. In this study, over 700 conventional and organic fresh produce buyers in the Boston area were surveyed for their perceived food safety risks. Survey results showed that consumers perceived relatively high risks associated with the consumption and production of conventionally grown produce compared with other public health hazards. For example, conventional and organic food buyers estimated the median annual fatality rate due to pesticide residues on conventionally grown food to be about 50 per million and 200 per million, respectively, which is similar in magnitude to the annual mortality risk from motor vehicle accidents in the United States. Over 90% of survey respondents also perceived a reduction in pesticide residue risk associated with substituting organically grown produce for conventionally grown produce, and nearly 50% perceived a risk reduction due to natural toxins and microbial pathogens. Multiple regression analyses indicate that only a few factors are consistently predictive of higher risk perceptions, including feelings of distrust toward regulatory agencies and the safety of the food supply. A variety of factors were found to be significant predictors of specific categories of food hazards, suggesting that consumers may view food safety risks as dissimilar from one another. Based on study findings, it is recommended that future agricultural policies and risk communication efforts utilize a comparative risk approach that targets a range of food safety hazards.",
"title": "Perceived risks of conventional and organic produce: pesticides, pathogens, and natural toxins."
},
{
"docid": "MED-2738",
"text": "Although survey results measuring the safety of consumers' food handling and risky food consumption practices have been published for over 20 years, evaluation of trends is impossible because the designs of published studies are not comparable. The Food Safety Surveys used comparable methods to interview U.S. adults by telephone in 1988, 1993, 2001, 2006, and 2010 about food handling (i.e., cross-contamination prevention) and risky consumption practices (eating raw or undercooked foods from animals) and perceived risk from foodborne illness. Sample sizes ranged from 1,620 to 4,547. Responses were analyzed descriptively, and four indices measuring meat, chicken, and egg cross-contamination, fish cross-contamination, risky consumption, and risk perceptions were analyzed using generalized linear models. The extent of media coverage of food safety issues was also examined. We found a substantial improvement in food handling and consumption practices and an increase in perceived risk from foodborne illness between 1993 and 1998. All indices were stable or declined between 1998 and 2006. Between 2006 and 2010, the two safe food handling practice indices increased significantly, but risk perceptions did not change, and safe consumption declined. Women had safer food handling and consumption practices than men. The oldest and youngest respondents and those with the highest education had the least safe food handling behaviors. Changes in safety of practices over the survey years are consistent with the change in the number of media stories about food safety in the periods between surveys. This finding suggests that increased media attention to food safety issues may raise awareness of food safety hazards and increase vigilance in food handling by consumers.",
"title": "Trends in U.S. consumers' safe handling and consumption of food and their risk perceptions, 1988 through 2010."
},
{
"docid": "MED-3486",
"text": "The Dietary Supplements Information Expert Committee (DSI-EC) of the United States Pharmacopeial Convention (USP) reviews the safety of dietary supplements and dietary supplement ingredients for the purpose of determining whether they should be admitted as quality monographs into the United States Pharmacopeia and National Formulary (USP-NF). The United States Food and Drug Administration (FDA) has enforcement authority to pursue a misbranding action in those instances where a dietary supplement product indicates that it conforms to USP standards but fails to so conform. Recently DSI-EC undertook a safety evaluation of spirulina, a widely used dietary ingredient. DSI-EC reviewed information from human clinical trials, animal studies, and regulatory and pharmacopeial sources and analyzed 31 adverse event reports regarding spirulina to assess potential health concerns. At the conclusion of this review, DSI-EC assigned a Class A safety rating for Spirulina maxima and S. platensis, thereby permitting the admission of quality monographs for these dietary supplement ingredients in USP-NF. DSI-EC continually monitors reports concerning the safety of dietary supplements and dietary supplement ingredients for which USP dietary supplement monographs are developed. The DSI-EC may revisit the safety classification of spirulina as new information on this dietary ingredient becomes available.",
"title": "United States pharmacopeia safety evaluation of spirulina."
},
{
"docid": "MED-702",
"text": "AIM OF THE REVIEW: To systematically analyze the efficacy and safety of liraglutide for the treatment of diabetes mellitus in comparison to other mono- and combination therapies. METHOD: PubMed (any date) and EMBASE (all years) search was conducted with liraglutide as a search term. Phase III clinical trials retrieved by the two databases and resources posted in Drug@FDA website were evaluated with regard to outcomes of efficacy and safety. RESULTS: Eight Phase III clinical studies compared the efficacy and safety of liraglutide to other monotherapies or combinations. Liraglutide as monotherapy in doses of 0.9 mg or above showed a significantly superior reduction in HbA1C compared to monotherapies with glimepiride or glyburide. When liraglutide was used as add-on therapy to glimepiride in doses of 1.2 mg or above, the reduction of HbA1C was greater than that in the combination therapy of glimepiride and rosiglitazone. However, liraglutide as add-on therapy to metformin failed to show benefit over combination of metformin and glimepiride. Triple therapy of using liraglutide in addition to metformin plus either glimepiride or rosiglitazone resulted in additional benefit in HbA1C reduction. Most common adverse events were gastrointestinal disturbance such as nausea, vomit, diarrhea, and constipation. During the eight clinical studies, six cases of pancreatitis and five cases of cancer were reported in liraglutide arm, whereas there was one case of each of pancreatitis in exenatide and glimepiride arms, respectively, and one case of cancer in metformin plus sitagliptin arm. CONCLUSION: Liraglutide is a new therapeutic option to improve glycemic control in patients with type 2 diabetes. However, the present lack of evidence of durability of efficacy and long-term safety appear to limit its utility in the general treatment of type 2 diabetes at this time.",
"title": "The efficacy and safety of liraglutide."
},
{
"docid": "MED-5347",
"text": "BACKGROUND: There has been increasing interest in the impact of resident-physician and nurse work hours on patient safety. The evidence demonstrates that work schedules have a profound effect on providers' sleep and performance, as well as on their safety and that of their patients. Nurses working shifts greater than 12.5 hours are at significantly increased risk of experiencing decreased vigilance on the job, suffering an occupational injury, or making a medical error. Physicians-in-training working traditional > 24-hour on-call shifts are at greatly increased risk of experiencing an occupational sharps injury or a motor vehicle crash on the drive home from work and of making a serious or even fatal medical error. As compared to when working 16-hours shifts, on-call residents have twice as many attentional failures when working overnight and commit 36% more serious medical errors. They also report making 300% more fatigue-related medical errors that lead to a patient's death. CONCLUSION: The weight of evidence strongly suggests that extended-duration work shifts significantly increase fatigue and impair performance and safety. From the standpoint of both providers and patients, the hours routinely worked by health care providers in the United States are unsafe. To reduce the unacceptably high rate of preventable fatigue-related medical error and injuries among health care workers, the United States must establish and enforce safe work-hour limits.",
"title": "Effects of health care provider work hours and sleep deprivation on safety and performance."
},
{
"docid": "MED-2725",
"text": "IMPORTANCE: Food and Drug Administration (FDA) guidance allows food manufacturers to determine whether additives to food are \"generally recognized as safe\" (GRAS). Manufacturers are not required to notify the FDA of a GRAS determination, although in some instances they notify the agency. The individuals that companies select to make these determinations may have financial conflicts of interest. OBJECTIVE: To determine the extent to which individuals selected by manufacturers to make GRAS determinations have conflicts of interest between their obligations to ensure that the use of the additive is safe and their financial relationships to the company. DESIGN Using conflict of interest criteria developed by a committee of the Institute of Medicine, we analyzed 451 GRAS notifications that were voluntarily submitted to the FDA between 1997 and 2012. MAIN OUTCOMES AND MEASURES: Number of GRAS notices submitted to the FDA; frequency of various types of relationships between decision maker and additive manufacturer; frequency of participation on GRAS panels by individuals; and number of GRAS safety determinations identified by the FDA that were not submitted to the agency. RESULTS: For the 451 GRAS notifications, 22.4% of the safety assessments were made by an employee of an additive manufacturer, 13.3% by an employee of a consulting firm selected by the manufacturer, and 64.3% by an expert panel selected by either a consulting firm or the manufacturer. A standing expert panel selected by a third party made none of these safety assessments. The 290 panels that made GRAS determinations had an average of 3.5 members, with a maximum of 7. Ten individuals served on 27 or more panels; 1 individual served on 128 panels (44.1%). At least 1 of the 10 individuals with the most frequent service was a member of 225 panels (77.6%). CONCLUSIONS AND RELEVANCE: Between 1997 and 2012, financial conflicts of interest were ubiquitous in determinations that an additive to food was GRAS. The lack of independent review in GRAS determinations raises concerns about the integrity of the process and whether it ensures the safety of the food supply, particularly in instances where the manufacturer does not notify the FDA of the determination. The FDA should address these concerns.",
"title": "Conflicts of interest in approvals of additives to food determined to be generally recognized as safe: out of balance."
},
{
"docid": "MED-4531",
"text": "Traditional herbal preparations used in Ayurveda, traditional Chinese medicine, traditional Tibetan medicine, and other Asian traditional medicine systems may contain significant amounts of mercury, arsenic or lead. Though deliberately incorporated in Asian traditional herbal preparations for therapeutic purposes, these constituents have caused intoxications worldwide. The aim of this study was therefore to determine mercury, arsenic, and lead levels in Asian traditional herbal preparations on the Dutch market. A total of 292 traditional herbal preparations used in Ayurveda, traditional Chinese medicine, and traditional Tibetan medicine were sampled between 2004 and 2007. Samples were mostly multi-ingredient traditional herbal preparations containing herbs and minerals. The labeling of less than 20% of the traditional herbal preparations suggested the presence of mercury, arsenic or lead. These elements were shown by inductively coupled mass spectrometry (ICP-MS) in 186 (64%) of 292 traditional herbal preparations. Estimated weekly mercury, arsenic, and lead intake levels were calculated for each traditional herbal preparation from the analytically determined concentrations and the recommended dose. A total of 59 traditional herbal preparations (20%) were likely to result in intakes of these elements significantly exceeding safety limits. Of these 59 traditional herbal preparations, intake estimates for 50 traditional herbal preparations significantly exceeded the safety limit for mercury (range = 1.4-1747 mg week(-1)); intake estimates for 26 traditional herbal preparations significantly exceeded the safety limit for arsenic (range = 0.53-427 mg week(-1)) and intake estimates for eight traditional herbal preparations were significantly above the safety limit for lead (range = 2.6-192 mg week(-1)). It is concluded that the mercury, arsenic, and lead contents of traditional herbal preparations used in Ayurveda, traditional Chinese medicine, and traditional Tibetan medicine remain a cause for concern and require strict control.",
"title": "Monitoring of mercury, arsenic, and lead in traditional Asian herbal preparations on the Dutch market and estimation of associated risks."
},
{
"docid": "MED-4205",
"text": "Since the Second World War the consumer behaviour in developed countries changed drastically. Primarily there existed the demand for sufficient food after a period of starvation, afterwards the desire for higher quality was arising, whereas today most people ask for safe and healthy food with high quality. Therefore a united approach comprising consistent standards, sound science and robust controls is required to ensure consumers' health and to maintain consumers' confidence and satisfaction. Chemical analysis along the whole food chain downstream (tracking) from primary production to the consumer and upstream (tracing) from the consumer to primary production is an important prerequisite to ensure food safety and quality. In this frame the focus of the following paper is the \"chemical safety of meat and meat products\" taking into account inorganic as well as organic residues and contaminants, the use of nitrite in meat products, the incidence of veterinary drugs, as well as a Failure Mode and Effect Analysis (FMEA) system assessing (prioritizing) vulnerable food chain steps to decrease or eliminate vulnerability.",
"title": "Chemical safety of meat and meat products."
},
{
"docid": "MED-5345",
"text": "Five years ago, the Institute of Medicine (IOM) called for a national effort to make health care safe. Although progress since then has been slow, the IOM report truly \"changed the conversation\" to a focus on changing systems, stimulated a broad array of stakeholders to engage in patient safety, and motivated hospitals to adopt new safe practices. The pace of change is likely to accelerate, particularly in implementation of electronic health records, diffusion of safe practices, team training, and full disclosure to patients following injury. If directed toward hospitals that actually achieve high levels of safety, pay for performance could provide additional incentives. But improvement of the magnitude envisioned by the IOM requires a national commitment to strict, ambitious, quantitative, and well-tracked national goals. The Agency for Healthcare Research and Quality should bring together all stakeholders, including payers, to agree on a set of explicit and ambitious goals for patient safety to be reached by 2010.",
"title": "Five years after To Err Is Human: what have we learned?"
},
{
"docid": "MED-4001",
"text": "Introduction. This is an open-label pilot study on four weeks of virgin coconut oil (VCO) to investigate its efficacy in weight reduction and its safety of use in 20 obese but healthy Malay volunteers. Methodology. Efficacy was assessed by measuring weight and associated anthropometric parameters and lipid profile one week before and one week after VCO intake. Safety was assessed by comparing organ function tests one week before and one week after intake of VCO. Paired t-test was used to analyse any differences in all the measurable variables. Results. Only waist circumference (WC) was significantly reduced with a mean reduction of 2.86 cm or 0.97% from initial measurement (P = .02). WC reduction was only seen in males (P < .05). There was no change in the lipid profile. There was a small reduction in creatinine and alanine transferase levels. Conclusion. VCO is efficacious for WC reduction especially in males and it is safe for use in humans.",
"title": "An Open-Label Pilot Study to Assess the Efficacy and Safety of Virgin Coconut Oil in Reducing Visceral Adiposity"
},
{
"docid": "MED-2807",
"text": "In a previous three-month study of Meriva, a proprietary curcumin-phosphatidylcholine phytosome complex, decreased joint pain and improvement in joint function were observed in 50 osteoarthritis (OA) patients. Since OA is a chronic condition requiring prolonged treatment, the long-term efficacy and safety of Meriva were investigated in a longer (eight months) study involving 100 OA patients. The clinical end points (Western Ontario and McMaster Universities [WOMAC] score, Karnofsky Performance Scale Index, and treadmill walking performance) were complemented by the evaluation of a series of inflammatory markers (interleukin [IL]-1beta, IL-6, soluble CD40 ligand [sCD40L], soluble vascular cell adhesion molecule (sVCAM)-1, and erythrocyte sedimentation rate [ESR]). This represents the most ambitious attempt, to date, to evaluate the clinical efficacy and safety of curcumin as an anti-inflammatory agent. Significant improvements of both the clinical and biochemical end points were observed for Meriva compared to the control group. This, coupled with an excellent tolerability, suggests that Meriva is worth considering for the long-term complementary management of osteoarthritis.",
"title": "Efficacy and safety of Meriva®, a curcumin-phosphatidylcholine complex, during extended administration in osteoarthritis patients."
},
{
"docid": "MED-2822",
"text": "Curcumin is known to possess potent antiinflammatory and antiarthritic properties. This pilot clinical study evaluated the safety and effectiveness of curcumin alone, and in combination with diclofenac sodium in patients with active rheumatoid arthritis (RA). Forty-five patients diagnosed with RA were randomized into three groups with patients receiving curcumin (500 mg) and diclofenac sodium (50 mg) alone or their combination. The primary endpoints were reduction in Disease Activity Score (DAS) 28. The secondary endpoints included American College of Rheumatology (ACR) criteria for reduction in tenderness and swelling of joint scores. Patients in all three treatment groups showed statistically significant changes in their DAS scores. Interestingly, the curcumin group showed the highest percentage of improvement in overall DAS and ACR scores (ACR 20, 50 and 70) and these scores were significantly better than the patients in the diclofenac sodium group. More importantly, curcumin treatment was found to be safe and did not relate with any adverse events. Our study provides the first evidence for the safety and superiority of curcumin treatment in patients with active RA, and highlights the need for future large-scale trials to validate these findings in patients with RA and other arthritic conditions. Copyright © 2012 John Wiley & Sons, Ltd.",
"title": "A randomized, pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis."
},
{
"docid": "MED-2618",
"text": "BACKGROUND: Food dyes, synthesized originally from coal tar and now petroleum, have long been controversial because of safety concerns. Many dyes have been banned because of their adverse effects on laboratory animals or inadequate testing. CONCLUSIONS: This review finds that all of the nine currently US-approved dyes raise health concerns of varying degrees. Red 3 causes cancer in animals, and there is evidence that several other dyes also are carcinogenic. Three dyes (Red 40, Yellow 5, and Yellow 6) have been found to be contaminated with benzidine or other carcinogens. At least four dyes (Blue 1, Red 40, Yellow 5, and Yellow 6) cause hypersensitivity reactions. Numerous microbiological and rodent studies of Yellow 5 were positive for genotoxicity. Toxicity tests on two dyes (Citrus Red 2 and Orange B) also suggest safety concerns, but Citrus Red 2 is used at low levels and only on some Florida oranges and Orange B has not been used for several years. The inadequacy of much of the testing and the evidence for carcinogenicity, genotoxicity, and hypersensitivity, coupled with the fact that dyes do not improve the safety or nutritional quality of foods, indicates that all of the currently used dyes should be removed from the food supply and replaced, if at all, by safer colorings. It is recommended that regulatory authorities require better and independent toxicity testing, exercise greater caution regarding continued approval of these dyes, and in the future approve only well-tested, safe dyes.",
"title": "Toxicology of food dyes."
},
{
"docid": "MED-1140",
"text": "Consumer concern over the quality and safety of conventional food has intensified in recent years, and primarily drives the increasing demand for organically grown food, which is perceived as healthier and safer. Relevant scientific evidence, however, is scarce, while anecdotal reports abound. Although there is an urgent need for information related to health benefits and/or hazards of food products of both origins, generalized conclusions remain tentative in the absence of adequate comparative data. Organic fruits and vegetables can be expected to contain fewer agrochemical residues than conventionally grown alternatives; yet, the significance of this difference is questionable, inasmuch as actual levels of contamination in both types of food are generally well below acceptable limits. Also, some leafy, root, and tuber organic vegetables appear to have lower nitrate content compared with conventional ones, but whether or not dietary nitrate indeed constitutes a threat to human health is a matter of debate. On the other hand, no differences can be identified for environmental contaminants (e.g. cadmium and other heavy metals), which are likely to be present in food from both origins. With respect to other food hazards, such as endogenous plant toxins, biological pesticides and pathogenic microorganisms, available evidence is extremely limited preventing generalized statements. Also, results for mycotoxin contamination in cereal crops are variable and inconclusive; hence, no clear picture emerges. It is difficult, therefore, to weigh the risks, but what should be made clear is that 'organic' does not automatically equal 'safe.' Additional studies in this area of research are warranted. At our present state of knowledge, other factors rather than safety aspects seem to speak in favor of organic food.",
"title": "Organic food: buying more safety or just peace of mind? A critical review of the literature."
},
{
"docid": "MED-913",
"text": "In recent years, there has been a notable concern on the safety of genetically modified (GM) foods/plants, an important and complex area of research, which demands rigorous standards. Diverse groups including consumers and environmental Non Governmental Organizations (NGO) have suggested that all GM foods/plants should be subjected to long-term animal feeding studies before approval for human consumption. In 2000 and 2006, we reviewed the information published in international scientific journals, noting that the number of references concerning human and animal toxicological/health risks studies on GM foods/plants was very limited. The main goal of the present review was to assess the current state-of-the-art regarding the potential adverse effects/safety assessment of GM plants for human consumption. The number of citations found in databases (PubMed and Scopus) has dramatically increased since 2006. However, new information on products such as potatoes, cucumber, peas or tomatoes, among others was not available. Corn/maize, rice, and soybeans were included in the present review. An equilibrium in the number research groups suggesting, on the basis of their studies, that a number of varieties of GM products (mainly maize and soybeans) are as safe and nutritious as the respective conventional non-GM plant, and those raising still serious concerns, was currently observed. Nevertheless, it should be noted that most of these studies have been conducted by biotechnology companies responsible of commercializing these GM plants. These findings suggest a notable advance in comparison with the lack of studies published in recent years in scientific journals by those companies. All this recent information is herein critically reviewed. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "A literature review on the safety assessment of genetically modified plants."
},
{
"docid": "MED-1811",
"text": "BACKGROUND: A growing number of preclinical studies have demonstrated that curcumin could be a promising anticancer drug; however, poor bioavailability has been the major obstacle for its clinical application. To overcome this problem, we developed a new form of curcumin (Theracurmin) and reported high plasma curcumin levels could be safely achieved after a single administration of Theracurmin in healthy volunteers. In this study, we aimed to evaluate the safety of repetitive administration of Theracurmin in cancer patients. METHODS: Pancreatic or biliary tract cancer patients who failed standard chemotherapy were eligible for this study. Based on our previous pharmacokinetic study, we selected Theracurmin containing 200 mg of curcumin (Level 1) as a starting dose, and the dose was safely escalated to Level 2, which contained 400 mg of curcumin. Theracurmin was orally administered every day with standard gemcitabine-based chemotherapy. In addition to safety and pharmacokinetics data, NF-κB activity, cytokine levels, efficacy, and quality-of-life score were evaluated. RESULTS: Ten patients were assigned to level 1 and six were to level 2. Peak plasma curcumin levels (median) after Theracurmin administration were 324 ng/mL (range, 47-1,029 ng/mL) at Level 1 and 440 ng/mL (range, 179-1,380 ng/mL) at Level 2. No unexpected adverse events were observed and 3 patients safely continued Theracurmin administration for >9 months. CONCLUSIONS: Repetitive systemic exposure to high concentrations of curcumin achieved by Theracurmin did not increase the incidence of adverse events in cancer patients receiving gemcitabine-based chemotherapy.",
"title": "A phase I study investigating the safety and pharmacokinetics of highly bioavailable curcumin (Theracurmin) in cancer patients."
},
{
"docid": "MED-4376",
"text": "OBJECTIVE: To study hair mercury concentrations among women of reproductive age in relation to fish intake in Ontario, Canada. STUDY DESIGN: Three groups were studied: 22 women who had called the Motherisk Program for information on the reproductive safety of consuming fish during pregnancy, a group of Japanese residing in Toronto (n=23) consuming much larger amounts of fish, and a group of Canadian women of reproductive age (n=20) not seeking advice, were studied. Mercury concentrations in hair samples were measured using inductively coupled plasma mass spectrometry. Seafood consumption habits were recorded for each participant. Based on the types of fish consumed and consumption frequencies, the estimated monthly intake of mercury was calculated. Hair mercury concentrations were correlated to both the number of monthly seafood servings and the estimated ingested mercury dose. RESULTS: There were significant correlations between fish servings and hair mercury (Spearman r=0.73, P<.0001) and between amounts of consumed mercury and hair mercury concentrations (Spearman r=0.81, P<.0001). Nearly two thirds of the Motherisk callers, all of the Japanese women, and 15% of the Canadian women of reproductive age had hair mercury above 0.3 microg/g, which was shown recently to be the lowest observable adverse effect level in a large systematic review of all perinatal studies. CONCLUSIONS: Because of very wide variability, general recommendations for a safe number of fish servings may not be sufficient to protect the fetus. Analysis of hair mercury may be warranted before pregnancy in selected groups of women consuming more than 12 ounces of fish per week, as dietary modification can decrease body burden and ensure fetal safety. Copyright (c) 2010. Published by Mosby, Inc.",
"title": "Hair mercury levels of women of reproductive age in Ontario, Canada: implications to fetal safety and fish consumption."
},
{
"docid": "MED-4456",
"text": "Broccoli sprouts are widely consumed in many parts of the world. There have been no reported concerns with respect to their tolerance and safety in humans. A formal phase I study of safety, tolerance, and pharmacokinetics appeared justified because these sprouts are being used as vehicles for the delivery of the glucosinolate glucoraphanin and its cognate isothiocyanate sulforaphane [1-isothiocyanato-(4R)-(methylsulfinyl)butane] in clinical trials. Such trials have been designed to evaluate protective efficacy against development of neoplastic and other diseases. A placebo-controlled, double-blind, randomized clinical study of sprout extracts containing either glucosinolates (principally glucoraphanin, the precursor of sulforaphane) or isothiocyanates (principally sulforaphane) was conducted on healthy volunteers who were in-patients on our clinical research unit. The subjects were studied in three cohorts, each comprising three treated individuals and one placebo recipient. Following a 5-day acclimatization period on a crucifer-free diet, the broccoli sprout extracts were administered orally at 8-h intervals for 7 days (21 doses), and the subjects were monitored during this period and for 3 days after the last treatment. Doses were 25 micromol of glucosinolate (cohort A), 100 micromol of glucosinolate (cohort B), or 25 micromol of isothiocyanate (cohort C). The mean cumulative excretion of dithiocarbamates as a fraction of dose was very similar in cohorts A and B (17.8 +/- 8.6% and 19.6 +/- 11.7% of dose, respectively) and very much higher and more consistent in cohort C (70.6 +/- 2.0% of dose). Thirty-two types of hematology or chemistry tests were done before, during, and after the treatment period. Indicators of liver (transaminases) and thyroid [thyroid-stimulating hormone, total triiodothyronine (T3), and free thyroxine (T4)] function were examined in detail. No significant or consistent subjective or objective abnormal events (toxicities) associated with any of the sprout extract ingestions were observed.",
"title": "Safety, tolerance, and metabolism of broccoli sprout glucosinolates and isothiocyanates: a clinical phase I study."
},
{
"docid": "MED-4987",
"text": "BACKGROUND: Cardiovascular disease is the leading cause of mortality among adults with Type 2 diabetes. The thiazolidinediones including rosiglitazone are approved for the treatment of Type 2 diabetes on the basis of their ability to lower blood sugar and surrogate markers of cardiovascular disease. OBJECTIVES: To ascertain the cardiovascular, skeletal and hematologic safety profile of rosiglitazone. METHODS: Synthesis of evidence from recent trials, systematic reviews, meta-analysis, regulatory documents and clinical trials registries of manufacturers. CONCLUSION: Rosiglitazone increases the risk of heart failure, myocardial infarction and fractures (in women) with Type 2 diabetes.",
"title": "The safety of rosiglitazone in the treatment of type 2 diabetes."
},
{
"docid": "MED-1600",
"text": "Over the past 10years there has been ongoing development of curing processes with natural ingredients designed to meet consumer demand and regulatory requirements for natural and organic processed meats. Initially, these processes utilized celery concentrates with a high nitrate content combined with a nitrate-reducing starter culture. Subsequent advances included celery concentrates with the nitrate converted to nitrite by suppliers. Further, as questions developed concerning reduced concentration of preservatives and the microbiological safety of these processed meats, additional advances have resulted in a wide variety of ingredients and processes designed to provide supplementary antimicrobial effects for improved product safety. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Beyond celery and starter culture: advances in natural/organic curing processes in the United States."
},
{
"docid": "MED-3487",
"text": "Weight loss supplements often contain powerful pharmacoactive ingredients with the potential to cause harm. Trials used to determine product safety and effectiveness, meanwhile, tend to be small, of short duration, and frequently lack financial conflict of interest disclosures. These factors could conspire to place consumers at risk, especially when published research cited in advertising cloaks products with the suggestion that their safety and effectiveness have been proven by science. Examples of current and former weight loss products backed by potentially conflicted or low quality research include Metabolife-356, Hydroxycut, Xenadrine and LeptiCore. Published research, especially in the field of weight loss supplements, needs better conflict of interest disclosure, and regulators should consider how research findings are used in marketing claims.",
"title": "Science of weight loss supplements: Compromised by conflicts of interest?"
},
{
"docid": "MED-914",
"text": "Chinese wild rice has been consumed for over 3000 years, but its safety as a food in China has never been established. The grain contains higher amounts of protein, ash and crude fibre than white rice. Levels of non-nutritive mineral elements such as arsenic, cadmium and lead are very low. The eating patterns of 110 people ( > 60 yr) showed no ill-effects. The results of acute toxicity tests with mice fed diet containing 21.5 g/kg Chinese wild rice [corrected] indicated no abnormal reaction and none of the mice died. The bone marrow micronucleus and sperm abnormality tests conducted with mice were negative as was the Salmonella mutagenicity test. The results of this investigation indicate that Chinese wild rice is safe for human consumption.",
"title": "Studies of the safety of Chinese wild rice."
},
{
"docid": "MED-5224",
"text": "Dry-eye syndrome (DES) is a multifactorial disease affecting millions of individuals worldwide. Various factors, including age, hormonal status, genetics, sex, immune status, innervation status, nutrition, pathogens, and environmental stress, can alter the cellular and molecular structure or function of components of the ocular surface system. The resulting imbalance increases susceptibility to desiccation and epithelial damage, leading to a vicious circle in which inflammation amplifies and sustains further damage by chronic deregulation of the system. Lubricating agents and steroids have been used as treatment options. However, as the causes of the disease become better elucidated, the more chemically complex cyclosporine A has become an increasingly useful treatment option and in the United States is currently the only Food and Drug Administration (FDA)-approved prescription drug for the treatment of dry eye. The safety and efficacy of cyclosporine have been shown in numerous studies.",
"title": "Safety and Efficacy of Cyclosporine in the Treatment of Chronic Dry Eye"
},
{
"docid": "MED-2428",
"text": "This paper is based on a longer report on the benefits, safety and modalities of information representation with regard to women and statin use, situated within the historical context of Women's Health Movement which has advocated for unbiased, appropriate medical research and prescribing for women based on the goals of full-disclosure, informed consent, evidence-based medicine and gender-based analysis. The evidence base for prescribing statins for women, especially for primary prevention is weak, yet Canadian data suggest that half of all prescriptions are for women. Safety meta-analyses do not disaggregate for women; do not consider female vulnerability to statin induced muscle problems, and women-centred concerns such as breast-cancer, miscarriage or birth defects are under-researched. Many trials have not published their non-cardiac serious adverse event data. These factors suggest that the standards of full-disclosure, informed consent, evidence-based prescribing and gender-based analysis are not being met and women should proceed with caution.",
"title": "Women and statin use: a women's health advocacy perspective."
},
{
"docid": "MED-3490",
"text": "Liquid dietary supplements represent a fast growing market segment, including botanically-based beverages containing mangosteen, acai, and noni. These products often resemble fruit juice in packaging and appearance, but may contain pharmacologically active ingredients. While little is known about the human health effects or safety of consuming such products, manufacturers make extensive use of low-quality published research to promote their products. This report analyzes the science-based marketing claims of two of the most widely consumed mangosteen liquid dietary supplements, and compares them to the findings of the research being cited. The reviewer found that analyzed marketing claims overstate the significance of findings, and fail to disclose severe methodological weaknesses of the research they cite. If this trend extends to other related products that are similarly widely consumed, it may pose a public health threat by misleading consumers into assuming that product safety and effectiveness are backed by rigorous scientific data.",
"title": "Science in Liquid Dietary Supplement Promotion: The Misleading Case of Mangosteen Juice"
},
{
"docid": "MED-2800",
"text": "The management of osteoarthritis represents a real challenge. This complex and multi-factorial disease evolves over decades and requires not only the alleviation of symptoms, i.e. pain and joint function but also the preservation of articular structure without side effects. Nutraceuticals are good candidates for the management of OA due to their safety profile and potential efficacy. However, they are not part of the treatment guidelines and published recommendations. Curcumin is the yellow pigment isolated from the rhizomes of Curcuma longa, commonly known as turmeric. Curcumin is a highly pleiotropic molecule with an excellent safety profile. Strong molecular evidence has been published for its potency to target multiple inflammatory diseases. However, naturally occurring curcumin cannot achieve its optimum therapeutic outcomes due to its low solubility and poor bioavailability. Nevertheless, curcumin presents great potential for treating OA and has been categorized as having preclinical evidence of efficacy. This review aimed at gathering most of the available information to document the potential efficacy of curcumin based on the results obtained in in vitro models of cartilage and osteoarthritis and in other diseases.",
"title": "Curcumin: a new paradigm and therapeutic opportunity for the treatment of osteoarthritis: curcumin for osteoarthritis management"
},
{
"docid": "MED-2254",
"text": "The aim of this study was to estimate the dietary cadmium (Cd) intake of the Belgian adult population, to compare this dietary Cd exposure to the tolerable weekly intake (TWI) recently established by the European Food Safety Authority (EFSA) and to determine the major food groups that contribute to dietary Cd exposure in Belgium. Food consumption data were derived from the 2004 Belgian food consumption survey (two 24 h recalls, 3083 participants). Cadmium concentrations in food items (n = 4000) were gathered from the control program of the Belgian Federal Agency for the Safety of the Food Chain for the period 2006-2008. Dietary intake per individual was calculated from consumption data and median Cd concentrations. The population mean, median and 95th percentile of the dietary intake values were 0.98, 0.85 and 2.02 µg kg⁻¹ body weight per week respectively. Two percent of the Belgian adult population has a dietary Cd intake above the recent TWI of 2.5 µg kg⁻¹ body weight established by EFSA in 2009. Cereal products and potatoes contribute for more than 60% to Cd intake.",
"title": "Dietary cadmium intake by the Belgian adult population."
},
{
"docid": "MED-4418",
"text": "Coumarin is a secondary phytochemical with hepatotoxic and carcinogenic properties. For the carcinogenic effect, a genotoxic mechanism was considered possible, but was discounted by the European Food Safety Authority in 2004 based on new evidence. This allowed the derivation of a tolerable daily intake (TDI) for the first time, and a value of 0.1 mg/kg body weight was arrived at based on animal hepatotoxicity data. However, clinical data on hepatotoxicity from patients treated with coumarin as medicinal drug is also available. This data revealed a subgroup of the human population being more susceptible for the hepatotoxic effect than the animal species investigated. The cause of the high susceptibility is currently unknown; possible mechanisms are discussed. Using the human data, a TDI of 0.1 mg/kg body weight was derived, confirming that of the European Food Safety Authority. Nutritional exposure may be considerably, and is mainly due to use of cassia cinnamon, which is a popular spice especially, used for cookies and sweet dishes. To estimate exposure to coumarin during the Christmas season in Germany, a telephone survey was performed with more than 1000 randomly selected persons. Heavy consumers of cassia cinnamon may reach a daily coumarin intake corresponding to the TDI.",
"title": "Toxicology and risk assessment of coumarin: focus on human data."
}
] |
PLAIN-2146
|
standard American diet
|
[
{
"docid": "MED-2819",
"text": "OBJECTIVES: Curcumin (diferuloylmethane) is the principal biochemical component of the spice turmeric and has been shown to possess potent anti-catabolic, anti-inflammatory and antioxidant, properties. This article aims to provide a summary of the actions of curcumin on articular chondrocytes from the available literature with the use of a text-mining tool. We highlight both the potential benefits and drawbacks of using this chemopreventive agent for treating osteoarthritis (OA). We also explore the recent literature on the molecular mechanisms of curcumin mediated alterations in gene expression mediated via activator protein 1 (AP-1)/nuclear factor-kappa B (NF-kappaB) signalling in chondrocytes, osteoblasts and synovial fibroblasts. METHODS: A computer-aided search of the PubMed/Medline database aided by a text-mining tool to interrogate the ResNet Mammalian database 6.0. RESULTS: Recent work has shown that curcumin protects human chondrocytes from the catabolic actions of interleukin-1 beta (IL-1beta) including matrix metalloproteinase (MMP)-3 up-regulation, inhibition of collagen type II and down-regulation of beta1-integrin expression. Curcumin blocks IL-1beta-induced proteoglycan degradation, AP-1/NF-kappaB signalling, chondrocyte apoptosis and activation of caspase-3. CONCLUSIONS: The available data from published in vitro and in vivo studies suggest that curcumin may be a beneficial complementary treatment for OA in humans and companion animals. Nevertheless, before initiating extensive clinical trials, more basic research is required to improve its solubility, absorption and bioavailability and gain additional information about its safety and efficacy in different species. Once these obstacles have been overcome, curcumin and structurally related biochemicals may become safer and more suitable nutraceutical alternatives to the non-steroidal anti-inflammatory drugs that are currently used for the treatment of OA. Copyright 2009 Osteoarthritis Research Society International. All rights reserved.",
"title": "Biological actions of curcumin on articular chondrocytes."
},
{
"docid": "MED-1412",
"text": "Mean faecal pH values did not differ significantly in groups of rural South African Black schoolchildren of 10--12 years who ate their traditional high-fibre low-fat diet, and urban dwellers who consumed a partially westernized diet. However, both means were significantly lower than those of groups of White schoolchildren. In feeding studies of 5 days' duration, mean faecal pH value of Black children became significantly less acid when white bread replaced maize meal, and became significantly more acid when a supplement of 6 oranges was consumed daily. Supplements which consisted of skim milk, butter, and sugar had no significant effect on mean faecal pH value. In White children in an institution, the mean pH value of faeces became significantly more acid when a supplement of 6 oranges, although not of bran 'crunchies', was consumed daily.",
"title": "Faecal pH value and its modification by dietary means in South African black and white schoolchildren."
},
{
"docid": "MED-4324",
"text": "BACKGROUND: Increasingly the potential harm from high cholesterol intake, and specifically from egg yolks, is considered insignificant. We therefore assessed total plaque area (TPA) in patients attending Canadian vascular prevention clinics to determine if the atherosclerosis burden, as a marker of arterial damage, was related to egg intake. To provide perspective on the magnitude of the effect, we also analysed the effect of smoking (pack-years). METHODS: Consecutive patients attending vascular prevention clinics at University Hospital had baseline measurement of TPA by duplex ultrasound, and filled out questionnaires regarding their lifestyle and medications, including pack-years of smoking, and the number of egg yolks consumed per week times the number of years consumed (egg-yolk years). RESULTS: Data were available in 1262 patients; mean (SD) age was 61.5 (14.8) years; 47% were women. Carotid plaque area increased linearly with age after age 40, but increased exponentially with pack-years of smoking and with egg-yolk years. Plaque area in patients consuming <2 eggs per week (n = 388) was 125 ± 129 mm(2), versus 132 ± 142 mm(2) in those consuming 3 or more eggs per week (n = 603); (p < 0.0001 after adjustment for age). In multiple regression, egg-yolk years remained significant after adjusting for coronary risk factors. INTERPRETATION: Our findings suggest that regular consumption of egg yolk should be avoided by persons at risk of cardiovascular disease. This hypothesis should be tested in a prospective study with more detailed information about diet, and other possible confounders such as exercise and waist circumference. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.",
"title": "Egg yolk consumption and carotid plaque."
},
{
"docid": "MED-3105",
"text": "The gastrointestinal tract is the central organ for uptake of fluids and nutrients, and at the same time it forms the main protective barrier between the sterile environment of the body and the outside world. In mammals, the intestine has further evolved to harbor a vast load of commensal bacteria that have important functions for the host. Discrimination by the host defense system of nonself from self can prevent invasion of pathogens, but equivalent responses to dietary or colonizing bacteria can lead to devastating consequences for the organism. This dilemma imposed by the gut environment has probably contributed significantly to the evolutionary drive that has led to sophisticated mechanisms and diversification of the immune system to allow for protection while maintaining the integrity of the mucosal barrier. The immense expansion and specialization of the immune system is particularly mirrored in the phylogeny, ontogeny, organization, and regulation of the adaptive intraepithelial lymphocytes, or IEL, which are key players in the unique intestinal defense mechanisms that have evolved in mammals.",
"title": "Starting at the beginning: new perspectives on the biology of mucosal T cells."
},
{
"docid": "MED-3220",
"text": "Background Maintaining muscle mass while aging is important to prevent falls and fractures. Metabolic acidosis promotes muscle wasting, and the net acid load from diets that are rich in net acid–producing protein and cereal grains relative to their content of net alkali–producing fruit and vegetables may therefore contribute to a reduction in lean tissue mass in older adults. Objective We aimed to determine whether there was an association of 24-h urinary potassium and an index of fruit and vegetable content of the diet with the percentage lean body mass (%LBM) or change in %LBM in older subjects. Design Subjects were 384 men and women ≥65 y old who participated in a 3-y trial comparing calcium and vitamin D with placebo. Potassium was measured in 24-h urine collections at baseline. The %LBM, defined as total body nonfat, nonbone tissue weight ÷ weight × 100, was measured by using dual-energy X-ray absorptiometry at baseline and at 3 y. Physical activity, height, and weight were assessed at baseline and at 3 y. Results At baseline, the mean urinary potassium excretion was 67.0 ± 21.1 mmol/d. Urinary potassium (mmol/d) was significantly positively associated with %LBM at baseline (β = 0.033, P = 0.006; adjusted for sex, weight, and nitrogen excretion) but not with 3-y change in %LBM. Over the 3-y study, %LBM increased by 2.6 ± 3.6%. Conclusion Higher intake of foods rich in potassium, such as fruit and vegetables, may favor the preservation of muscle mass in older men and women.",
"title": "Alkaline diets favor lean tissue mass in older adults"
},
{
"docid": "MED-3878",
"text": "Diet, nutritional status, and certain dietary supplements are postulated to influence the development and progression of prostate cancer. Angiogenesis and inflammation are central to tumor growth and progression, but the effect of diet on these processes remains uncertain. We explored changes in 50 plasma cytokines and angiogenic factors (CAFs) in 145 men with prostate cancer enrolled in a pre-operative, randomized controlled phase-II trial with four arms: control (usual diet); low-fat (LF) diet; flaxseed-supplemented (FS) diet; and flaxseed-supplemented, low-fat diet. The mean duration of dietary intervention was 30–31 days. Among the individual arms, the largest number of significant changes (baseline vs pre-operative follow-up) was observed in the LF arm, with 19 CAFs decreasing and one increasing (p<.05). Compared to the control arm, 6 CAFs—including pro-angiogenic factors (stromal-cell derived-1α and myeloid factors (granulocyte-colony-stimulating factor, macrophage colony-stimulating factor — all decreased in the LF arm compared to controls; 3 and 4 CAFs changed in the FS and FS+LF arms, respectively. Weight loss occurred in the LF arms and significantly correlated with VEGF decreases (P <0.001). The CAFs that changed in the LF arm are all known to be regulated by nuclear factor-kappa B (NF-κB), and a pathway analysis identified NF-κB as the most likely regulatory network associated with these changes in the LF arm, but not in the FS-containing arms. These results suggest that a low-fat diet without flaxseed may reduce levels of specific inflammatory cytokines and angiogenic factors and suggests that the NF-κB pathway may be a mediator of these changes.",
"title": "Effect of Low-fat Diets on Plasma Levels of NFκB-regulated Inflammatory Cytokines and Angiogenic Factors in Men with Prostate Cancer"
},
{
"docid": "MED-2126",
"text": "Increased protein supply by feeding cow-milk-based infant formula in comparison to lower protein content of human milk is a well-recognized major risk factor of childhood obesity. However, there is yet no conclusive biochemical concept explaining the mechanisms of formula-induced childhood obesity. It is the intention of this article to provide the biochemical link between leucine-mediated signalling of mammalian milk proteins and adipogenesis as well as early adipogenic programming. Leucine has been identified as the predominant signal transducer of mammalian milk, which stimulates the nutrient-sensitive kinase mammalian target of rapamycin complex 1 (mTORC1). Leucine thus functions as a maternal-neonatal relay for mTORC1-dependent neonatal β-cell proliferation and insulin secretion. The mTORC1 target S6K1 plays a pivotal role in stimulation of mesenchymal stem cells to differentiate into adipocytes and to induce insulin resistance. It is of most critical concern that infant formulas provide higher amounts of leucine in comparison to human milk. Exaggerated leucine-mediated mTORC1-S6K1 signalling induced by infant formulas may thus explain increased adipogenesis and generation of lifelong elevated adipocyte numbers. Attenuation of mTORC1 signalling of infant formula by leucine restriction to physiologic lower levels of human milk offers a great chance for the prevention of childhood obesity and obesity-related metabolic diseases.",
"title": "Excessive Leucine-mTORC1-Signalling of Cow Milk-Based Infant Formula: The Missing Link to Understand Early Childhood Obesity"
},
{
"docid": "MED-4424",
"text": "OBJECTIVES: Atherosclerosis can obstruct branching arteries of the abdominal aorta, including four paired lumbar arteries and the middle sacral artery that feed the lumbar spine. The diminished blood flow could result in various back problems. The aim of this systematic literature review was to assess associations between atherosclerosis and disc degeneration (DD) or low-back pain (LBP). DATA SOURCES: A systematic search of the Medline/PubMed database for all original articles on atherosclerosis and DD/LBP published until October 2008. The search was performed with the medical subject headings atherosclerosis, cardiovascular risk factor, or vascular disease and keywords \"disc degeneration\", \"disc herniation\", and \"back pain\" on the basis of MeSH tree and as a text search. In addition reference lists were studied and searched manually. Observational studies investigating the association of atherosclerosis or its risk factors and lumbar DD/LBP were selected. REVIEW METHODS: The following data were extracted: study characteristics, duration of follow-up, year of publication, findings of atherosclerosis/cardiovascular risk factors and DD/LBP. Disc herniation was regarded as a form of disc degeneration and cardiovascular risk factors were regarded as surrogate for atherosclerosis in epidemiological studies. RESULTS: One hundred and seventy-nine papers were identified. After exclusion of case reports, letters, editorials, papers not related to the lumbar spine, and animal studies, 25 papers were included. Post-mortem studies showed an association between atheromatous lesions in the aorta and DD, as well as between occluded lumbar arteries and life-time LBP. In clinical studies, aortic calcification was associated with LBP, and stenosis of lumbar arteries was associated with both DD and LBP. In epidemiological studies, smoking and high serum cholesterol levels were found to have the most consistent associations with DD and LBP. CONCLUSION: Aortic atherosclerosis and stenosis of the feeding arteries of the lumbar spine were associated with DD and LBP. Cardiovascular risk factors had weaker associations, being clearly apparent only in cohorts on elderly people or in large study samples. More prospective clinical studies are needed to further clarify the association of atherosclerosis and low-back disorders.",
"title": "Atherosclerosis and disc degeneration/low-back pain--a systematic review."
},
{
"docid": "MED-1814",
"text": "Pancreatic cancer is highly lethal, and identifying modifiable risk factors could have substantial public health impact. In this population-based case-control study (532 cases, 1701 controls), we used principal component analysis and multivariable unconditional logistic regression models to examine whether a particular dietary pattern was associated with risk of pancreatic cancer, adjusting for other known risk factors. A Prudent dietary pattern, characterized by greater intake of vegetables, fruit, fish, poultry, whole grains, and low-fat dairy, was associated with an approximate 50% reduction in pancreatic cancer risk among men (OR=0.51, 95% CI 0.31-0.84, p-trend=0.001) and women (OR=0.51, 95% CI 0.29-0.90, p-trend=0.04). A Western dietary pattern, characterized by higher intake of red and processed meats, potato chips, sugary beverages, sweets, high fat dairy, eggs, and refined grains, was associated with a 2.4-fold increased risk of pancreatic cancer among men (95% CI 1.3-4.2, p-trend=0.008); but was not associated with risk among women. Among men, those in the upper quintiles of the Western diet and lower quintiles of the Prudent diet had a 3-fold increased risk. Consistent with what has been recommended for several other chronic diseases, consuming a diet rich in plant-based foods, whole grains, and white meat, might reduce risk of pancreatic cancer.",
"title": "Dietary patterns and risk of pancreatic cancer in a large population-based case-control study in the San Francisco Bay Area"
},
{
"docid": "MED-1503",
"text": "Epidemiologic studies suggest that dietary lutein and zeaxanthin may be of benefit in maintaining cognitive health. Among the carotenoids, lutein and zeaxanthin are the only two that cross the blood-retina barrier to form macular pigment (MP) in the eye. They also preferentially accumulate in the human brain. Lutein and zeaxanthin in macula from nonhuman primates were found to be significantly correlated with their concentrations in matched brain tissue. Therefore, MP can be used as a biomarker of lutein and zeaxanthin in primate brain tissue. This is of interest given that a significant correlation was found between MP density and global cognitive function in healthy older adults. An examination of a relation between cognition and lutein and zeaxanthin concentrations in the brain tissue of decedents from a population-based study in centenarians found that zeaxanthin concentrations in brain tissue were significantly related to antemortem measures of global cognitive function, memory retention, verbal fluency, and dementia severity after adjustment for age, sex, education, hypertension, and diabetes. In univariate analyses, lutein was related to recall and verbal fluency, but the strength of the associations was attenuated with adjustment for covariates. However, lutein concentrations in the brain were significantly lower in individuals with mild cognitive impairment than in those with normal cognitive function. Last, in a 4-mo, double-blinded, placebo-controlled trial in older women that involved lutein supplementation (12 mg/d), alone or in combination with DHA (800 mg/d), verbal fluency scores improved significantly in the DHA, lutein, and combined-treatment groups. Memory scores and rate of learning improved significantly in the combined-treatment group, who also showed a trend toward more efficient learning. When all of these observations are taken into consideration, the idea that lutein and zeaxanthin can influence cognitive function in older adults warrants further study.",
"title": "A possible role for lutein and zeaxanthin in cognitive function in the elderly."
},
{
"docid": "MED-4476",
"text": "Total N-nitroso compounds (NOC) and NOC precursors (NOCP) were determined in extracts of food and tobacco products. Following Walters' method, NOC were decomposed to NO with refluxing HBr/HCl/HOAc/EtOAc and NO was measured by chemiluminescence. NOC were determined after sulfamic acid treatment to destroy nitrite, and NOCP were determined after treatment with 110 mM nitrite and then sulfamic acid. Analysis without HBr gave results < or =20% of those with HBr. This NOC method was efficient for nitrosamines but not nitrosoureas. The standard nitrosation for determining NOCP gave high yields for readily nitrosated amines, including 1-deoxy-1-fructosylvaline, but not for simple amines, dipeptides, and alkylureas. Mean NOC and NOCP results were (respectively, in micromol/kg of product) 5.5 and 2700 for frankfurters, 0.5 and 660 for fresh meat, 5.8 and 5800 for salted, dried fish, and 660 and 2900 for chewing tobacco (all for aqueous extracts) and 220 and 20000 nmol/cigarette for MeCN extracts of cigarette smoke filter pads.",
"title": "Determination of total N-nitroso compounds and their precursors in frankfurters, fresh meat, dried salted fish, sauces, tobacco, and tobacco smoke ..."
},
{
"docid": "MED-3798",
"text": "The Moos Menstrual Distress Questionnaire (MMDQ) was completed by thirty healthy premenopausal women randomized into one of two sets of weight-maintaining diets, those with a ratio of polyunsaturated to saturated fatty acids (P/S ratio) of 1.0 and those with a P/S ratio of 0.3. After a baseline interval of one menstrual cycle, both groups were fed a high fat diet (40% energy from fat) for four menstrual cycles per subject, followed by a similar interval on a low fat diet (20% energy from fat). There were no significant differences in self-reported menstrual symptoms between the two P/S groups. During both menses and the premenstrual week of the low fat dietary period there were significant decreases in self-reported symptoms associated with water retention. A decrease in symptoms in the group labelled \"arousal\" during the rest of the menstrual cycle was also reported.",
"title": "Influence of dietary fat on self-reported menstrual symptoms."
},
{
"docid": "MED-1867",
"text": "OBJECTIVES: There is increasing evidence that intake of sour tea (Hibiscus sabdariffa) has hypoglycemic and hypolipidemic effects and may benefit patients suffering from metabolic disorders such as diabetes. The objective of the present study was to investigate the hypolipidemic effects of sour tea in patients with diabetes and compare them with those of black tea. DESIGN: In this sequential randomized controlled clinical trial, 60 patients with diabetes were recruited and randomly assigned into two groups: sour tea (ST) and black tea (BT). They were instructed to consume sour tea or black tea two times a day for 1 month. OUTCOME MEASURES: Fasting blood samples were taken at the beginning and at the end of the study for evaluation of lipids, lipoproteins, and apoproteins. RESULTS: Fifty-three (53) patients concluded the study. In the ST group, mean of high-density lipoprotein-cholesterol (HDLc) increased significantly (p = 0.002) at the end of the study, whereas changes in apolipoprotein-A1, and lipoprotein (a) were not significant. Also, a significant decrease in the mean of total cholesterol, low density lipoprotein-cholesterol, triglycerides, and Apo-B100 were seen in this group. In the BT group, only HDLc showed significant change (p = 0.002) at the end of the study and changes in the other measures were not statistically significant. CONCLUSIONS: The results of the present study showed that ST has a significant effect on blood lipid profile in patients with diabetes.",
"title": "Effects of sour tea (Hibiscus sabdariffa) on lipid profile and lipoproteins in patients with type II diabetes."
},
{
"docid": "MED-2802",
"text": "OBJECTIVE: The objective of this study was to determine the efficacy and safety of Curcuma domestica extracts in pain reduction and functional improvement in patients with knee osteoarthritis. STUDY DESIGN AND SETTING: The design and setting were a randomized controlled study at a university hospital in Bangkok, Thailand. METHODS: One-hundred and seven (107) patients with primary knee osteoarthritis (OA) with pain score of > or =5 were randomized to receive ibuprofen 800 mg per day or C. domestica extracts 2 g per day for 6 weeks. The main outcomes were improvement in pain on level walking, pain on stairs, and functions of knee assessed by time spent during 100-m walk and going up and down a flight of stairs. The adverse events were also recorded. RESULTS: Fifty-two (52) and 55 patients were randomized to C. domestica extracts and ibuprofen groups, respectively. Baseline characteristics of the patients in both groups were not different. The mean scores of the aforementioned outcomes at weeks 0, 2, 4, and 6 were significantly improved when compared with the baseline values in both groups. There was no difference in those parameters between the patients receiving ibuprofen and C. domestica extracts, except pain on stairs (p = 0.016). No significant difference of adverse events between both groups was found (33.3% versus 44.2%, p = 0.36 in C. domestica extracts and ibuprofen groups, respectively). CONCLUSIONS: C. domestica extracts seem to be similarly efficacious and safe as ibuprofen for the treatment of knee OA.",
"title": "Efficacy and safety of Curcuma domestica extracts in patients with knee osteoarthritis."
},
{
"docid": "MED-2181",
"text": "Background Little is known about the impact of location of food consumption and preparation upon daily energy intake for children. Objective To examine trends in daily energy intake by children for foods eaten at home or away-from-home, by source of preparation, and for combined categories of eating location and food source. Subjects The analysis uses data from 29,217 children aged 2–18 years from the 1977–1978 Nationwide Food Consumption Survey, 1989–1991 and 1994–1998 Continuing Survey of Food Intake by Individuals, and 2003–2006 National Health and Nutrition Examination Surveys. Methods Nationally representative weighted percentages and means of daily energy intake by eating location were analyzed for trends from 1977 to 2006. Comparisons by food source were examined from 1994 to 2006. Analyses were repeated for 3 age groups: 2–6, 7–12, and 13–18 year olds. Difference testing was conducted using a t test. Results Increased energy intake (+179 kcal/d) by children from 1977–2006 was associated with a major increase in calories eaten away-from-home (+255 kcal/d). The percentage of kcal/d eaten away-from-home increased from 23.4% to 33.9% from 1977–2006. No further increase was observed from 1994–2006, but the sources of calories shifted. The percentage of calories from fast food increased to surpass intake from schools and become the largest contributor to foods prepared away-from-home for all age groups. For foods eaten away-from-home, the percentage of kcal/d from stores increased to become the largest source of calories eaten away-from-home. Fast food eaten at home and store-bought food eaten away-from-home increased significantly. Conclusion Eating location and food source significantly impact daily energy intake for children. Foods prepared away-from-home, including fast food eaten at home and store-prepared food eaten away-from-home, are fueling the increase in total calorie intake. However, further research using alternative data sources is necessary to verify that store-bought foods eaten away-from-home are increasingly store-prepared.",
"title": "Trends in energy intake among US children by eating location and food source, 1977–2006"
},
{
"docid": "MED-4451",
"text": "Research leading to the discovery of a series of mutagenic and carcinogenic heterocyclic amines (HCAs) was inspired by the idea that smoke produced during cooking of food, especially meat or fish, might be carcinogenic. More than ten kinds of HCAs, actually produced by cooking or heating of meat or fish, have now been isolated and their structures determined, most being previously unregistered compounds. They are highly mutagenic towards Salmonella typhimurium in the presence of S9 mix and are also mutagenic in vitro and in vivo toward mammalian cells. HCAs have now been chemically synthesized in quantity and subjected to long-term animal testing. When HCAs were fed in the diet, rodents developed cancers in many organs, including the colon, breast and prostate, and one HCA produced hepatomas in monkeys. The lesions exhibited alteration in genes including Apc, beta-catenin and Ha-ras, and these changes provide clues to the induction mechanisms. The HCAs are oxidized to hydroxyamino derivatives by cytochrome P450s, and further converted to ester forms by acetyltransferase and sulfotransferase. Eventually, they produce DNA adducts through the formation of N-C bonds at guanine bases. There are HCA-sensitive and resistant strains of rodents and a search for the responsible genes is now under way. While the content of HCAs in dishes consumed in ordinary life is low and not sufficient in itself to explain human cancer, the coexistence of many other mutagens/carcinogens of either autobiotic or xenobiotic type and the possibility that HCAs induce genomic instability and heightened sensitivity to tumor promoters suggest that avoidance of exposure to HCAs or reduction of HCAs' biological effects as far as possible are to be highly recommended. Usage of microwave ovens for cooking and supplementation of the diet, for example with soy-isoflavones, which have been found to suppress the occurrence of HCA-induced breast cancers, should be encouraged. Advice to the general public about how to reduce the carcinogenic load imposed by HCAs would be an important contribution to cancer prevention.",
"title": "Heterocyclic amines: Mutagens/carcinogens produced during cooking of meat and fish."
},
{
"docid": "MED-3228",
"text": "A precise understanding of the role of dietary protein in bone health has been evasive despite decades of research. It is known that a dietary acid load is harmful to bone, and sulfur-containing amino acids are metabolized to provide such an acid load. It is also known that protein elevates urine calcium loss. However, recent clinical studies and a meta-analysis have indicated either no effect or a modest benefit associated with higher protein intakes. These contradictory considerations may be explained by the existence of a two-faced relationship between protein and bone, with simultaneous positive and negative pathways. In opposition to the negative effects of dietary acid load, protein may exert positive effects related to improving calcium absorption, increasing insulin-like growth factor 1, or improving lean body mass, which, in turn, improves bone strength. Putative mechanisms behind these pathways are reviewed here, and some limitations in the historical literature as well as suggested measures to counter these in the future are identified. When positive and negative pathways are considered in tandem, protein may offer modest benefits to bone in the presence of adequate dietary calcium and acid-neutralizing fruits and vegetables. © 2011 International Life Sciences Institute.",
"title": "Dietary protein and bone health: harmonizing conflicting theories."
},
{
"docid": "MED-2583",
"text": "Inositol hexaphosphate (IP(6)), a naturally polyphosphorylated carbohydrate, has been reported to have significant in vivo and in vitro anticancer activity against numerous tumours, such as colon, prostate, breast, liver and rhabdomyosarcomas. To confirm this activity in haematological malignancies and to characterize some of the mechanisms of IP(6) action, we analysed its effects on human leukaemic cell lines and fresh chronic myelogenous leukaemia (CML) progenitor cells using a combined cellular and molecular approach. IP(6) had a dose-dependent cytotoxic effect on all of the evaluated cell lines, with accumulation in the G2M phase in two out of five cell lines tested. At the molecular level, cDNA microarray analysis after IP(6) exposure showed an extensive downmodulation of genes involved in transcription and cell cycle regulation and a coherent upregulation of cell cycle inhibitors. Furthermore, IP(6) treatment of fresh leukaemic samples of bone marrow CD34+ CML progenitor cells significantly inhibited granulocyte-macrophage colony-forming unit (CFU-GM) formation (P = 0.0062) in comparison to normal bone marrow specimens, which were not affected. No differentiating effect on HL60 cells was observed. Taken together, our results confirm the antiproliferative activity of IP(6) and suggest that it may have a specific antitumour effect also in chronic myeloid leukaemias, via active gene modulation.",
"title": "Effect of inositol hexaphosphate (IP(6)) on human normal and leukaemic haematopoietic cells."
},
{
"docid": "MED-1818",
"text": "PURPOSE: Few data are available on the role of combinations of foods and/or nutrients on pancreatic cancer risk. To add further information on dietary patterns potentially associated to pancreatic cancer, we applied an exploratory principal component factor analysis on 28 major nutrients derived from an Italian case-control study. METHODS: Cases were 326 incident pancreatic cancer cases and controls 652 frequency-matched controls admitted to hospital for non-neoplastic diseases. Dietary information was collected through a validated and reproducible food frequency questionnaire. Multiple logistic regression models adjusted for sociodemographic variables and major recognized risk factors for pancreatic cancer were used to estimate the odds ratios (OR) of pancreatic cancer for each dietary pattern. RESULTS: We identified four dietary patterns-named \"animal products,\" \"unsaturated fats,\" \"vitamins and fiber,\" and \"starch rich,\" that explain 75% of the total variance in nutrient intake in this population. After allowing for all the four patterns, positive associations were found for the animal products and the starch rich patterns, the OR for the highest versus the lowest quartiles being 2.03 (95% confidence interval [CI], 1.29-3.19) and 1.69 (95% CI, 1.02-2.79), respectively; an inverse association emerged for the vitamins and fiber pattern (OR, 0.55; 95% CI, 0.35-0.86), whereas no association was observed for the unsaturated fats pattern (OR, 1.13; 95% CI, 0.71-1.78). CONCLUSIONS: A diet characterized by a high consumption of meat and other animal products, as well as of (refined) cereals and sugars, is positively associated with pancreatic cancer risk, whereas a diet rich in fruit and vegetables is inversely associated. Copyright © 2013 Elsevier Inc. All rights reserved.",
"title": "Nutrient-based dietary patterns and pancreatic cancer risk."
},
{
"docid": "MED-1186",
"text": "We investigated the effect of resistant starch (RS) on markers of colonic protein metabolism. Eleven subjects participated in a randomized crossover study in which they consumed either high-RS (39 +/- 3 g/d, -chi +/- SEM) or low-RS (5 +/- 0.4 g/d) diets for 3 wk. All other macronutrients were kept constant. During the high-RS diet daily excretion of fecal nitrogen increased from 1.84 +/- 0.15 to 2.86 +/- 0.42 g/d (P < 0.01) and excretion of fecal phenols fell from 9.2 +/- 1.4 to 5.3 +/- 0.8 mg/d (P < 0.01). Fecal concentrations of ammonia decreased from 397 +/- 33 to 278 +/- 49 microgram/g (P < 0.01) and phenols decreased from 69 +/- 8 to 39 +/- 10 microgram/g (P < 0.001). Daily output of urinary ammonia, urea, phenols, and total nitrogen did not change significantly, but pH decreased from 6.4 +/- 0.1 to 6.2 +/- 0.1 (P < 0.05) during the high-RS period. These results suggest that RS significantly attenuates the accumulation of potentially harmful byproducts of protein fermentation in the human colon.",
"title": "Resistant starch lowers fecal concentrations of ammonia and phenols in humans."
},
{
"docid": "MED-3279",
"text": "Various pesticides are being used to destabilize, perturb, or inhibit crucial biochemical and physiological targets related to metabolism, growth, development, nervous communication, or behavior in pestiferous organisms. Chitin is an eukaryotic extracellular aminosugar biopolymer, massively produced by most fungal systems and by invertebrates, notably arthropods. Being an integral supportive component in fungal cell wall, insect cuticle, and nematode egg shell, chitin has been considered as a selective target for pesticide action. Throughout the elaborate processes of chitin formation and deposition, only the polymerization events associated with the cell membrane compartment are so far available for chemical interference. Currently, the actinomycetes-derived nucleoside peptide fungicides such as the polyoxins and the insecticidal benzoylaryl ureas have reached commercial pesticide status. The polyoxins and other structurally-related antibiotics like nikkomycins are strong competitive inhibitors of the polymerizing enzyme chitin synthase. The exact biochemical lesion inflicted by the benzoylaryl ureas is still elusive, but a post-polymerization event, such as translocation of chitin chains across the cell membrane, is suggested. Hydrolytic degradation of the chitin polymer is essential for hyphal growth, branching, and septum formation in fungal systems as well as for the normal molting of arthropods. Recently, insect chitinase activity was strongly and specifically suppressed by allosamidin, an actimomycetes-derived metabolite. In part, the defense mechanism in plants against invasion of pathogens is associated with induced chitinases. Chitin, chitosan, and their oligomers are able to act as elicitors which induce enhanced levels of chitinases in various plants. Lectins which bind to N-acetyl-D-glucosamine strongly interfere with fungal and insect chitin synthases. Plant lectins with similar properties may be involved in plant-pathogen interaction inter alia by suppressing fungal invasion.",
"title": "Chitin synthesis and degradation as targets for pesticide action."
},
{
"docid": "MED-1659",
"text": "STUDY DESIGN: A histologic study on age-related changes of the human lumbar intervertebral disc was conducted. OBJECTIVES: To investigate comprehensively age-related temporospatial histologic changes in human lumbar intervertebral disc, and to develop a practicable and reliable classification system for age-related histologic disc alteration. SUMMARY OF THE BACKGROUND DATA: No comprehensive microscopic analysis of age-related disc changes is available. There is no conceptual morphologic framework for classifying age-related disc changes as a reference basis for more sophisticated molecular biologic analyses of the causative factors of disc aging or premature aging (degeneration). METHODS: A total of 180 complete sagittal lumbar motion segment slices obtained from 44 deceased individuals (fetal to 88 years of age) were analyzed with regard to 11 histologic variables for the intervertebral disc and endplate, respectively. In addition, 30 surgical specimens (3 regions each) were investigated with regard to five histologic variables. Based on the semiquantitative analyses of 20,250 histologic variable assessments, a classification system was developed and tested in terms of validity, practicability, and reliability. The classification system was applied to cadaveric and surgical disc specimens not included in the development of the classification system, and the scores were assessed by two additional independent raters. RESULTS: A semiquantitative analyses provided clear histologic evidence for the detrimental effect of a diminished blood supply on the endplate, resulting in the tissue breakdown beginning in the nucleus pulposus and starting in the second life decade. Significant temporospatial variations in the presence and abundance of histologic disc alterations were observed across levels, regions, macroscopic degeneration grades, and age groups. A practicable classification system for age-related histologic disc alterations was developed, resulting in moderate to excellent reliability (kappa values, 0.49-0.98) depending on the histologic variable. Application of the classification system to cadaveric and surgical specimens demonstrated a significant correlation with age ( < 0.0001) and macroscopic grade of degeneration ( < 0001). However, substantial data scatter caution against reliance on traditional macroscopic disc grading and favor a histology-based classification system as a reference standard. CONCLUSIONS: Histologic disc alterations can reliably be graded based on the proposed classification system providing a morphologic framework for more sophisticated molecular biologic analyses of factors leading to age-related disc changes. Diminished blood supply to the intervertebral disc in the first half of the second life decade appears to initiate tissue breakdown.",
"title": "Classification of age-related changes in lumbar intervertebral discs: 2002 Volvo Award in basic science."
},
{
"docid": "MED-2809",
"text": "Extensive research over the past half century has shown that curcumin (diferuloylmethane), a component of the golden spice turmeric (Curcuma longa), can modulate multiple cell signaling pathways. Extensive clinical trials over the past quarter century have addressed the pharmacokinetics, safety, and efficacy of this nutraceutical against numerous diseases in humans. Some promising effects have been observed in patients with various pro-inflammatory diseases including cancer, cardiovascular disease, arthritis, uveitis, ulcerative proctitis, Crohn’s disease, ulcerative colitis, irritable bowel disease, tropical pancreatitis, peptic ulcer, gastric ulcer, idiopathic orbital inflammatory pseudotumor, oral lichen planus, gastric inflammation, vitiligo, psoriasis, acute coronary syndrome, atherosclerosis, diabetes, diabetic nephropathy, diabetic microangiopathy, lupus nephritis, renal conditions, acquired immunodeficiency syndrome, β-thalassemia, biliary dyskinesia, Dejerine-Sottas disease, cholecystitis, and chronic bacterial prostatitis. Curcumin has also shown protection against hepatic conditions, chronic arsenic exposure, and alcohol intoxication. Dose-escalating studies have indicated the safety of curcumin at doses as high as 12 g/day over 3 months. Curcumin’s pleiotropic activities emanate from its ability to modulate numerous signaling molecules such as pro-inflammatory cytokines, apoptotic proteins, NF–κB, cyclooxygenase-2, 5-LOX, STAT3, C-reactive protein, prostaglandin E2, prostate-specific antigen, adhesion molecules, phosphorylase kinase, transforming growth factor-β, triglyceride, ET-1, creatinine, HO-1, AST, and ALT in human participants. In clinical trials, curcumin has been used either alone or in combination with other agents. Various formulations of curcumin, including nanoparticles, liposomal encapsulation, emulsions, capsules, tablets, and powder, have been examined. In this review, we discuss in detail the various human diseases in which the effect of curcumin has been investigated.",
"title": "Therapeutic Roles of Curcumin: Lessons Learned from Clinical Trials"
},
{
"docid": "MED-4220",
"text": "OBJECTIVE: Accumulating evidence indicates that prostate cancer is associated with high levels of serum IGF-I. This study was conducted to determine whether a low-fat diet and exercise (DE) intervention may modulate the IGF axis and reduce prostate cancer cell growth in vitro. METHODS: Fasting serum was obtained from 14 men (age 60 +/- 3 years) participating in an 11-day DE program and from eight similarly aged men who had followed the DE program for 14.2 +/- 1.7 years (long-term). Insulin, IGF-I, IGFBP-1, and IGFBP-3 were measured by ELISA, and serum was used to stimulate LNCaP cell growth in vitro. RESULTS: Serum IGF-I levels decreased by 20% while IGFBP-1 increased by 53% after 11-day DE. In the long-term group, IGF-I was 55% lower, while IGFBP-1 was 150% higher relative to baseline. Serum insulin decreased by 25% after 11-day DE and was 68% lower in the long-term group, relative to baseline. No changes in serum IGFBP-3 were observed. Serum-stimulated LNCaP cell growth was reduced by 30% in post-11-day serum and by 44% in long-term serum relative to baseline. LNCaP cells incubated with post-DE serum showed increased apoptosis/ necrosis, compared to baseline. CONCLUSIONS: A low-fat diet and exercise intervention induces in-vivo changes in the circulating IGF axis and is associated with reduced growth and enhanced apoptosis/necrosis of LNCaP tumor cells in vitro.",
"title": "Effect of diet and exercise on serum insulin, IGF-I, and IGFBP-1 levels and growth of LNCaP cells in vitro (United States)."
},
{
"docid": "MED-4233",
"text": "OBJECTIVES: Dietary fat and fiber affect hormonal levels and may influence cancer progression. Flaxseed is a rich source of lignan and omega-3 fatty acids and may thwart prostate cancer. The potential effects of flaxseed may be enhanced with concomitant fat restriction. We undertook a pilot study to explore whether a flaxseed-supplemented, fat-restricted diet could affect the biomarkers of prostatic neoplasia. METHODS: Twenty-five patients with prostate cancer who were awaiting prostatectomy were instructed on a low-fat (20% of kilocalories or less), flaxseed-supplemented (30 g/day) diet. The baseline and follow-up levels of prostate-specific antigen, testosterone, free androgen index, and total serum cholesterol were determined. The tumors of diet-treated patients were compared with those of historic cases (matched by age, race, prostate-specific antigen level at diagnosis, and biopsy Gleason sum) with respect to apoptosis (terminal deoxynucleotidyl transferase [TdT]-mediated dUTP-biotin nick end-labeling [TUNEL]) and proliferation (MIB-1). RESULTS: The average duration on the diet was 34 days (range 21 to 77), during which time significant decreases were observed in total serum cholesterol (201 +/- 39 mg/dL to 174 +/- 42 mg/dL), total testosterone (422 +/- 122 ng/dL to 360 +/- 128 ng/dL), and free androgen index (36.3% +/- 18.9% to 29.3% +/- 16.8%) (all P <0.05). The baseline and follow-up levels of prostate-specific antigen were 8.1 +/- 5.2 ng/mL and 8.5 +/- 7.7 ng/mL, respectively, for the entire sample (P = 0.58); however, among men with Gleason sums of 6 or less (n = 19), the PSA values were 7.1 +/- 3.9 ng/mL and 6.4 +/- 4.1 ng/mL (P = 0.10). The mean proliferation index was 7.4 +/- 7.8 for the historic controls versus 5.0 +/- 4.9 for the diet-treated patients (P = 0.05). The distribution of the apoptotic indexes differed significantly (P = 0.01) between groups, with most historic controls exhibiting TUNEL categorical scores of 0; diet-treated patients largely exhibited scores of 1. Both the proliferation rate and apoptosis were significantly associated with the number of days on the diet (P = 0.049 and P = 0.017, respectively). CONCLUSIONS: These pilot data suggest that a flaxseed-supplemented, fat-restricted diet may affect prostate cancer biology and associated biomarkers. Further study is needed to determine the benefit of this dietary regimen as either a complementary or preventive therapy.",
"title": "Pilot study of dietary fat restriction and flaxseed supplementation in men with prostate cancer before surgery: exploring the effects on hormonal l..."
},
{
"docid": "MED-2109",
"text": "Thirty-nine newborn infants with severe persistent pulmonary hypertension and respiratory failure who met criteria for 85% likelihood of dying were enrolled in a randomized trial in which extracorporeal membrane oxygenation (ECMO) therapy was compared with conventional medical therapy (CMT). In phase I, 4 of 10 babies in the CMT group died and 9 of 9 babies in the ECMO group survived. Randomization was halted after the fourth CMT death, as planned before initiating the study, and the next 20 babies were treated with ECMO (phase II). Of the 20, 19 survived. All three treatment groups (CMT and ECMO in phase I and ECMO, phase II) were comparable in severity of illness and mechanical ventilator support. The overall survival of ECMO-treated infants was 97% (28 of 29) compared with 60% (6 of 10) in the CMT group (P less than .05).",
"title": "Extracorporeal membrane oxygenation and conventional medical therapy in neonates with persistent pulmonary hypertension of the newborn: a prospecti..."
},
{
"docid": "MED-1209",
"text": "BACKGROUND: Lifestyle choices are associated with cardiovascular disease and mortality. The purpose of this study was to compare adherence to healthy lifestyle habits in adults between 1988 and 2006. METHODS: Analysis of adherence to 5 healthy lifestyle trends (>or=5 fruits and vegetables/day, regular exercise >12 times/month, maintaining healthy weight [body mass index 18.5-29.9 kg/m(2)], moderate alcohol consumption [up to 1 drink/day for women, 2/day for men] and not smoking) in the National Health and Nutrition Examination Survey 1988-1994 were compared with results from the National Health and Nutrition Examination Survey 2001-2006 among adults aged 40-74 years. RESULTS: Over the last 18 years, the percent of adults aged 40-74 years with a body mass index >or=30 kg/m(2) has increased from 28% to 36% (P <.05); physical activity 12 times a month or more has decreased from 53% to 43% (P <.05); smoking rates have not changed (26.9% to 26.1%); eating 5 or more fruits and vegetables a day has decreased from 42% to 26% (P <.05), and moderate alcohol use has increased from 40% to 51% (P <.05). Adherence to all 5 healthy habits has gone from 15% to 8% (P <.05). Although adherence to a healthy lifestyle was lower among minorities, adherence decreased more among non-Hispanic Whites over the period. Individuals with a history of hypertension/diabetes/cardiovascular disease were no more likely to be adherent to a healthy lifestyle than people without these conditions. CONCLUSIONS: Generally, adherence to a healthy lifestyle pattern has decreased during the last 18 years, with decreases documented in 3 of 5 healthy lifestyle habits. These findings have broad implications for the future risk of cardiovascular disease in adults.",
"title": "Adherence to healthy lifestyle habits in US adults, 1988-2006."
},
{
"docid": "MED-3237",
"text": "The modern Western-type diet is deficient in fruits and vegetables and contains excessive animal products, generating the accumulation of non-metabolizable anions and a lifespan state of overlooked metabolic acidosis, whose magnitude increases progressively with aging due to the physiological decline in kidney function. In response to this state of diet-derived metabolic acidosis, the kidney implements compensating mechanisms aimed to restore the acid-base balance, such as the removal of the non-metabolizable anions, the conservation of citrate, and the enhancement of kidney ammoniagenesis and urinary excretion of ammonium ions. These adaptive processes lower the urine pH and induce an extensive change in urine composition, including hypocitraturia, hypercalciuria, and nitrogen and phosphate wasting. Low urine pH predisposes to uric acid stone formation. Hypocitraturia and hypercalciuria are risk factors for calcium stone disease. Even a very mild degree of metabolic acidosis induces skeletal muscle resistance to the insulin action and dietary acid load may be an important variable in predicting the metabolic abnormalities and the cardiovascular risk of the general population, the overweight and obese persons, and other patient populations including diabetes and chronic kidney failure. High dietary acid load is more likely to result in diabetes and systemic hypertension and may increase the cardiovascular risk. Results of recent observational studies confirm an association between insulin resistance and metabolic acidosis markers, including low serum bicarbonate, high serum anion gap, hypocitraturia, and low urine pH. Copyright © 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.",
"title": "Diet-induced metabolic acidosis."
},
{
"docid": "MED-1667",
"text": "Non-specific low back pain has become a major public health problem worldwide. The lifetime prevalence of low back pain is reported to be as high as 84%, and the prevalence of chronic low back pain is about 23%, with 11-12% of the population being disabled by low back pain. Mechanical factors, such as lifting and carrying, probably do not have a major pathogenic role, but genetic constitution is important. History taking and clinical examination are included in most diagnostic guidelines, but the use of clinical imaging for diagnosis should be restricted. The mechanism of action of many treatments is unclear, and effect sizes of most treatments are low. Both patient preferences and clinical evidence should be taken into account for pain management, but generally self-management, with appropriate support, is recommended and surgery and overtreatment should be avoided. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Non-specific low back pain."
},
{
"docid": "MED-1863",
"text": "IMPORTANCE Previous studies have suggested an association between vegetarian diets and lower blood pressure (BP), but the relationship is not well established. OBJECTIVE To conduct a systematic review and meta-analysis of controlled clinical trials and observational studies that have examined the association between vegetarian diets and BP. DATA SOURCES MEDLINE and Web of Science were searched for articles published in English from 1946 to October 2013 and from 1900 to November 2013, respectively. STUDY SELECTION All studies met the inclusion criteria of the use of (1) participants older than 20 years, (2) vegetarian diets as an exposure or intervention, (3) mean difference in BP as an outcome, and (4) a controlled trial or observational study design. In addition, none met the exclusion criteria of (1) use of twin participants, (2) use of multiple interventions, (3) reporting only categorical BP data, or (4) reliance on case series or case reports. DATA EXTRACTION AND SYNTHESIS Data collected included study design, baseline characteristics of the study population, dietary data, and outcomes. The data were pooled using a random-effects model. MAIN OUTCOMES AND MEASURES Net differences in systolic and diastolic BP associated with the consumption of vegetarian diets were assessed. RESULTS Of the 258 studies identified, 7 clinical trials and 32 observational studies met the inclusion criteria. In the 7 controlled trials (a total of 311 participants; mean age, 44.5 years), consumption of vegetarian diets was associated with a reduction in mean systolic BP (-4.8 mm Hg; 95% CI, -6.6 to -3.1; P < .001; I2 = 0; P = .45 for heterogeneity) and diastolic BP (-2.2 mm Hg; 95% CI, -3.5 to -1.0; P < .001; I2 = 0; P = .43 for heterogeneity) compared with the consumption of omnivorous diets. In the 32 observational studies (a total of 21,604 participants; mean age, 46.6 years), consumption of vegetarian diets was associated with lower mean systolic BP (-6.9 mm Hg; 95% CI, -9.1 to -4.7; P < .001; I2 = 91.4; P < .001 for heterogeneity) and diastolic BP (-4.7 mm Hg; 95% CI, -6.3 to -3.1; P < .001; I2 = 92.6; P < .001 for heterogeneity) compared with the consumption of omnivorous diets. CONCLUSIONS AND RELEVANCE Consumption of vegetarian diets is associated with lower BP. Such diets could be a useful nonpharmacologic means for reducing BP.",
"title": "Vegetarian diets and blood pressure: a meta-analysis."
},
{
"docid": "MED-1212",
"text": "BACKGROUND: Many public health recommendations and clinical guidelines emphasize the importance of healthy lifestyles. Recent epidemiologic studies demonstrate that following a healthy lifestyle has substantial health benefits. The objectives of this study were to report on the prevalence of healthy lifestyle characteristics (HLCs) and to generate a single indicator of a healthy lifestyle. METHODS: National data for the year 2000 were obtained from the Behavioral Risk Factor Surveillance System, which consists of annual, statewide, random digit-dialed household telephone surveys. We defined the following 4 HLCs: nonsmoking, healthy weight (body mass index [calculated as weight in kilograms divided by the square of height in meters] of 18.5-25.0), consuming 5 or more fruits and vegetables per day, and regular physical activity (> or =30 minutes for > or =5 times per week). The 4 HLCs were summed to create a healthy lifestyle index (range, 0-4), and the pattern of following all 4 HLCs was defined as a single healthy lifestyle indicator. We report prevalences of each HLC and the indicator by major demographic subgroups. RESULTS: By using data from more than 153 000 adults, the prevalence (95% confidence interval) of the individual HLCs was as follows: nonsmoking, 76.0% (75.6%-76.4%); healthy weight, 40.1% (39.7%-40.5%); 5 fruits and vegetables per day, 23.3% (22.9%-23.7%); and regular physical activity, 22.2% (21.8%-22.6%). The overall prevalence of the healthy lifestyle indicator (ie, having all 4 HLCs) was only 3.0% (95% confidence interval, 2.8%-3.2%), with little variation among subgroups (range, 0.8%-5.7%). CONCLUSION: These data illustrate that a healthy lifestyle-defined as a combination of 4 HLCs-was undertaken by very few adults in the United States, and that no subgroup followed this combination to a level remotely consistent with clinical or public health recommendations.",
"title": "Healthy lifestyle characteristics among adults in the United States, 2000."
},
{
"docid": "MED-1401",
"text": "The link between iron intake as well as body iron stores and coronary heart disease (CHD) has been contentiously debated, and the epidemiologic evidence is inconsistent. We aimed to quantitatively summarize the literature on the association between dietary iron intake/body iron stores and CHD risk by conducting a meta-analysis of prospective cohort studies. PubMed was used to find studies published through June 2013 in peer-reviewed journals. Embase or a hand search of relevant articles was used to obtain additional articles. The pooled RRs of CHD incidence and mortality with 95% CIs were calculated by using either a random-effects or fixed-effects model, as appropriate. Twenty-one eligible studies (32 cohorts) including 292,454 participants with an average of 10.2 y of follow-up were included. Heme iron was found to be positively associated with CHD incidence (RR: 1.57; 95% CI: 1.28, 1.94), whereas total iron was inversely associated (RR: 0.85; 95% CI: 0.73, 0.999). Neither heme-iron nor total iron intakes were significantly associated with CHD mortality. Both transferrin saturation and serum iron were inversely related to CHD incidence [RR (95% CI): 0.76 (0.66, 0.88) and 0.68 (0.56, 0.82), respectively], but only transferrin saturation was inversely associated with CHD mortality (RR: 0.85; 95% CI: 0.73, 0.99). In conclusion, total iron intake and serum iron concentrations were inversely associated with CHD incidence, but heme iron intake was positively related to CHD incidence. Elevated serum transferrin saturation concentration was inversely associated with both CHD incidence and mortality. Future research is needed to establish the causal relation and to elucidate potential mechanisms.",
"title": "Dietary Iron Intake and Body Iron Stores Are Associated with Risk of Coronary Heart Disease in a Meta-Analysis of Prospective Cohort Studies"
},
{
"docid": "MED-3445",
"text": "A population-based case-control interview study was designed to test the hypothesis that dietary iodine or the consumption of goitrogenic vegetables increases the risk of thyroid cancer. A total of 191 histologically confirmed cases (64 percent female) and 441 matched controls from five ethnic groups in Hawaii were available for analysis. Among women, intake of seafood (especially shellfish), harm ha (a fermented fish sauce), and dietary iodine were associated with an increased risk of cancer, whereas consumption of goitrogenic (primarily cruciferous) vegetables was associated with a decreased risk. Non-dietary risk factors included miscarriage (especially at first pregnancy), use of fertility drugs, family history of thyroid disease, obesity, and work as a farm laborer. The odds ratio for the combined effect of a high iodine intake and a first-pregnancy miscarriage was 4.8 (95 percent confidence interval [CI] = 1.2-19.2); and for high iodine intake and use of fertility drugs 7.3 (95 percent CI = 1.5-34.5). Among men, positive associations were found for obesity, work as a farm laborer, and a past history of benign thyroid disease. Although this study identified several dietary and non-dietary risk factors for thyroid cancer, it could not fully explain the exceptionally high incidence rates among Filipino women in Hawaii.",
"title": "An epidemiologic study of thyroid cancer in Hawaii."
},
{
"docid": "MED-1409",
"text": "This study compares the prevalence of coronary heart disease (CHD), risk factors (RF), and cardiovascular diseases (CVD) among Cretan men from a rural area examined in 1960 and 1991. The study population consisted of 148 men in 1960 and 42 men in 1991 of the same age group (fifty-five to fifty-nine years old) and from the same rural area. All men had a complete examination of the cardiovascular system and a resting electrocardiogram (ECG). Systolic BP (SBP) > or = 140 mmHg was found in 42.6% of the subjects in 1960 and in 45.2% in 1991 (NS). Diastolic BP > or = 95 mmHG was found in 14.9% of the subjects in 1960 as opposed to 33.3% in 1991 (P < 0.02). Total serum cholesterol (TSCH) > or = 260 mg/dL approximately 6.7 mmol/L) was found in 12.8% of the subjects in 1960 and in 28.6% in 1991 (P < 0.01). Heavy smokers ( > or = 20 cigarettes/daily) were 27.0% in 1960 as compared with 35.7% in 1991 (:NS); 5.4% of the subjects in 1960 had light physical activity (PA) as compared with 14.3% in 1991 (P < 0.01); 74.7% of the subjects were farmers in 1960 as compared with 43.6% in 1991 (P < 0.1). The prevalence of CHD was 0.7% in 1960 as compared with 9.5% in 1991 (P < 0.001). Hypertensive heart disease was found in 3.4% of the subjects in 1960 and 4.8% in 1991 (NS). The prevalence of all major CVD was much higher in 1991 (19.1%) as compared with 1960 (8.8%) (P < 0.01). In conclusion, the prevalence of CHD RF and CVD was much higher in 1991 than in 1960 for Cretan men of the same age group. This higher prevalence seems to be related to dietary and life-style changes that have taken place in Crete during the last thirty years.",
"title": "Changing prevalence of coronary heart disease risk factors and cardiovascular diseases in men of a rural area of Crete from 1960 to 1991."
},
{
"docid": "MED-3139",
"text": "Background: Soy isoflavones have antiestrogenic and anticancer properties but also possess estrogen-like properties, which has raised concern about soy food consumption among breast cancer survivors. Objective: We prospectively evaluated the association between postdiagnosis soy food consumption and breast cancer outcomes among US and Chinese women by using data from the After Breast Cancer Pooling Project. Design: The analysis included 9514 breast cancer survivors with a diagnosis of invasive breast cancer between 1991 and 2006 from 2 US cohorts and 1 Chinese cohort. Soy isoflavone intake (mg/d) was measured with validated food-frequency questionnaires. HRs and 95% CIs were estimated by using delayed-entry Cox regression models, adjusted for sociodemographic, clinical, and lifestyle factors. Results: After a mean follow-up of 7.4 y, we identified 1171 total deaths (881 from breast cancer) and 1348 recurrences. Despite large differences in soy isoflavone intake by country, isoflavone consumption was inversely associated with recurrence among both US and Chinese women, regardless of whether data were analyzed separately by country or combined. No heterogeneity was observed. In the pooled analysis, consumption of ≥10 mg isoflavones/d was associated with a nonsignificant reduced risk of all-cause (HR: 0.87; 95% CI: 0.70, 1.10) and breast cancer–specific (HR: 0.83; 95% CI: 0.64, 1.07) mortality and a statistically significant reduced risk of recurrence (HR: 0.75; 95% CI: 0.61, 0.92). Conclusion: In this large study of combined data on US and Chinese women, postdiagnosis soy food consumption of ≥10 mg isoflavones/d was associated with a nonsignificant reduced risk of breast cancer–specific mortality and a statistically significant reduced risk of recurrence. One of the studies included in the After Breast Cancer Pooling Project, the Women's Healthy Eating & Living Study, was registered at clinicaltrials.gov as NCT00003787.",
"title": "Soy food intake after diagnosis of breast cancer and survival: an in-depth analysis of combined evidence from cohort studies of US and Chinese women"
},
{
"docid": "MED-2574",
"text": "Inositol hexaphosphate (IP(6)) is a naturally occurring polyphosphorylated carbohydrate, abundantly present in many plant sources and in certain high-fiber diets, such as cereals and legumes. In addition to being found in plants, IP(6) is contained in almost all mammalian cells, although in much smaller amounts, where it is important in regulating vital cellular functions such as signal transduction, cell proliferation, and differentiation. For a long time IP(6) has been recognized as a natural antioxidant. Recently IP(6) has received much attention for its role in cancer prevention and control of experimental tumor growth, progression, and metastasis. In addition, IP(6) possesses other significant benefits for human health, such as the ability to enhance immune system, prevent pathological calcification and kidney stone formation, lower elevated serum cholesterol, and reduce pathological platelet activity. In this review we show the efficacy and discuss some of the molecular mechanisms that govern the action of this dietary agent. Exogenously administered IP(6) is rapidly taken up into cells and dephosphorylated to lower inositol phosphates, which further affect signal transduction pathways resulting in cell cycle arrest. A striking anticancer action of IP(6) was demonstrated in different experimental models. In addition to reducing cell proliferation, IP(6) also induces differentiation of malignant cells. Enhanced immunity and antioxidant properties also contribute to tumor cell destruction. Preliminary studies in humans show that IP(6) and inositol, the precursor molecule of IP(6), appear to enhance the anticancer effect of conventional chemotherapy, control cancer metastases, and improve quality of life. Because it is abundantly present in regular diet, efficiently absorbed from the gastrointestinal tract, and safe, IP(6) + inositol holds great promise in our strategies for cancer prevention and therapy. There is clearly enough evidence to justify the initiation of full-scale clinical trials in humans.",
"title": "Protection against cancer by dietary IP6 and inositol."
},
{
"docid": "MED-1668",
"text": "Diffusion is the only source of nutrition to the intervertebral discs, and alteration of diffusion is considered to be the final common pathway for disc degeneration. Yet diffusion remains poorly understood due to the paucity of reliable methods to study diffusion noninvasively in humans in vivo. In recent years, postcontrast MRI has emerged as a powerful and reliable tool for analyzing diffusion in lumbar discs. Since it is noninvasive and safe, it can be used to document the process of diffusion temporally over a period of 24 hours. Well-designed studies have shown that diffusion is a very slow process, and that the endplate is the main structure that controls the process of diffusion. Contrast MRI studies have also made it possible to identify endplate breaks in vivo. In the future this technique may be applied to study the influence of smoking, mechanical loading of the discs, abnormal posture, and atherosclerosis of the lumbar arteries on diffusion. These conditions have all been implicated in disc degeneration through a final common pathway of altered diffusion and decreased nutrition. This review article focuses on the current knowledge, methodology, various factors that influence the diffusion properties of the discs, and future applications of this promising technique. (c) 2007 Wiley-Liss, Inc.",
"title": "Review of postcontrast MRI studies on diffusion of human lumbar discs."
},
{
"docid": "MED-2215",
"text": "We investigated the relationship between animal product consumption and evidence of dementia in two cohort substudies. The first enrolled 272 California residents matched for age, sex, and zip code (1 vegan, 1 lacto-ovo-vegetarian, and 2 'heavy' meat eaters in each of 68 quartets). This design ensured a wide range of dietary exposure. The second included 2,984 unmatched subjects who resided within the Loma Linda, California area. All subjects were enrolled in the Adventist Health Study. The matched subjects who ate meat (including poultry and fish) were more than twice as likely to become demented as their vegetarian counterparts (relative risk 2.18, p = 0.065) and the discrepancy was further widened (relative risk 2.99, p = 0.048) when past meat consumption was taken into account. There was no significant difference in the incidence of dementia in the vegetarian versus meat-eating unmatched subjects. There was no obvious explanation for the difference between the two substudies, although the power of the unmatched sub-study to detect an effect of 'heavy' meat consumption was unexpectedly limited. There was a trend towards delayed onset of dementia in vegetarians in both substudies.",
"title": "The incidence of dementia and intake of animal products: preliminary findings from the Adventist Health Study."
},
{
"docid": "MED-4520",
"text": "Evidence suggests that endothelial dysfunction is on the causal pathway for both atherogenesis and destabilization of established plaques. In this review, the role of flow-mediated dilatation (FMD) as a non-invasive method to assess endothelial function is discussed. Technical modifications and development of analysis software have significantly improved the variability of the method. Following a strict standardized protocol enables reproducible measurements to be achieved and export of the technique from specialized laboratories to population studies and multicentre settings. Endothelial function assessed by FMD has been shown to be affected by cardiovascular risk factors, to be related to structural arterial disease and to cardiovascular outcome, validating its use for studying the pathophysiology of arterial disease. Numerous studies have also demonstrated that it is responsive to physiological and pharmacological interventions. Flow-mediated dilatation provides unique opportunities in drug development programmes to assess an early rapidly responsive signal of risk or benefit, complementing endpoints of structural arterial disease and cardiovascular outcomes that take much longer and are more expensive.",
"title": "Assessment of atherosclerosis: the role of flow-mediated dilatation."
},
{
"docid": "MED-2295",
"text": "BACKGROUND: Intake of dietary fiber has been recommended for many years as part of the guidelines from the American Heart Association, the Institute of Medicine, and other groups. The recommended Adequate Intake for dietary fiber for adults is 25 to 38 g/day (14 g/1,000 kcal/day). OBJECTIVE: To determine the average daily intake of dietary fiber among adults during the past decade and, specifically, to document progress toward national goals. DESIGN: Cross-sectional weighted data from the National Health and Nutrition Examination Survey among adults aged 18 years and older. PARTICIPANTS/SETTING: Data were collected from noninstitutionalized adults aged 18 years and older using a nationally representative, complex, multistage, probability-based survey of people living in the United States that was conducted by the National Center for Health Statistics. MAIN OUTCOME MEASURES: Daily dietary fiber intake by members of the US population based on 2-year groupings of the continuous survey from 1999 to 2008. RESULTS: Mean daily dietary fiber intake for 1999-2000 was 15.6 g/day, for 2001-2002 intake was 16.1g/day, for 2003-2004 intake was 15.5 g/day, for 2005-2006 intake was 15.8 g/day, and for 2007-2008 intake was 15.9 g/day. Participants with obesity (body mass index ≥30) consistently reported lower fiber intake than did individuals with normal weight or overweight (14.6 to 15.4 g/day and 15.6 to 16.8 g/day, respectively; P<0.0001). Mexican Americans had significantly higher intake in 1999-2000 than non-Hispanic whites (18.0 vs 16.1g/day; P<0.05), but Mexican Americans' intake did not increase over time (17.7 g/day in 2007-2008). Non-Hispanic blacks had fiber intake of 12.5 g/day at baseline that increased modestly to 13.1 g/day by 2007-2008. CONCLUSIONS: Daily fiber intake generally has not progressed toward national goals during the past decade, but there are some differences according to health and social factors. Additional clinical practice and public health strategies are needed. Copyright © 2012 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.",
"title": "Trends in dietary fiber intake in the United States, 1999-2008."
},
{
"docid": "MED-1415",
"text": "BACKGROUND/OBJECTIVES: Consisting of ≈10(14) microbial cells, the intestinal microbiota represents the largest and the most complex microbial community inhabiting the human body. However, the influence of regular diets on the microbiota is widely unknown. SUBJECTS/METHODS: We examined faecal samples of vegetarians (n=144), vegans (n=105) and an equal number of control subjects consuming ordinary omnivorous diet who were matched for age and gender. We used classical bacteriological isolation, identification and enumeration of the main anaerobic and aerobic bacterial genera and computed absolute and relative numbers that were compared between groups. RESULTS: Total counts of Bacteroides spp., Bifidobacterium spp., Escherichia coli and Enterobacteriaceae spp. were significantly lower (P=0.001, P=0.002, P=0.006 and P=0.008, respectively) in vegan samples than in controls, whereas others (E. coli biovars, Klebsiella spp., Enterobacter spp., other Enterobacteriaceae, Enterococcus spp., Lactobacillus spp., Citrobacter spp. and Clostridium spp.) were not. Subjects on a vegetarian diet ranked between vegans and controls. The total microbial count did not differ between the groups. In addition, subjects on a vegan or vegetarian diet showed significantly (P=0.0001) lower stool pH than did controls, and stool pH and counts of E. coli and Enterobacteriaceae were significantly correlated across all subgroups. CONCLUSIONS: Maintaining a strict vegan or vegetarian diet results in a significant shift in the microbiota while total cell numbers remain unaltered.",
"title": "A vegan or vegetarian diet substantially alters the human colonic faecal microbiota."
},
{
"docid": "MED-3791",
"text": "Experimental and epidemiological evidence suggest that a diet with dietary fat as low as 20% of kcal may be necessary to reduce the risk of breast cancer. Two groups of women, postmenopausal women treated for breast cancer and premenopausal women with cystic breast disease accompanied by cyclical mastaligia, participated in an intervention program to determine the feasibility of such a low-fat diet. After 3 mo of intervention both groups were consuming a low-fat diet; in the premenopausal groups serum estrogen levels decreased in response to the fat reduction. Other nutrition-education programs in research institutions, restaurants, and schools are attempting to influence the public's knowledge and behavior regarding the importance of dietary fat reduction.",
"title": "Recommendations for the prevention of chronic disease: the application for breast disease."
},
{
"docid": "MED-4846",
"text": "The effects of a strict uncooked vegan diet on serum lipid and sterol concentrations were studied in patients with rheumatoid arthritis. The subjects were randomized into a vegan diet group (n 16), who consumed a vegan diet for 2-3 months, or into a control group (n 13), who continued their usual omnivorous diets. Serum total and LDL-cholesterol and -phospholipid concentrations were significantly decreased by the vegan diet. The levels of serum cholestanol and lathosterol also decreased, but serum cholestanol:total cholesterol and lathosterol:total cholesterol did not change. The effect of a vegan diet on serum plant sterols was divergent as the concentration of campesterol decreased while that of sitosterol increased. This effect resulted in a significantly greater sitosterol:campesterol value in the vegan diet group than in the control group (1.48 (SD 0.39) v. 0.72 (SD 0.14); P < 0.001). A higher concentration of campesterol compared with sitosterol is normal in omnivorous subjects and can be explained by lower absorption and esterification rates of sitosterol. Our results suggest that a strict uncooked vegan diet changes the relative absorption rates of these sterols and/or their biliary clearance.",
"title": "Divergent changes in serum sterols during a strict uncooked vegan diet in patients with rheumatoid arthritis."
},
{
"docid": "MED-3701",
"text": "Estrogen synthesized in situ plays a more important role in breast cancer cell proliferation than does circulating estrogen. Aromatase is the enzyme that converts androgen to estrogen and is expressed at a higher level in breast cancer tissue than in surrounding noncancer tissue. A promising route of chemoprevention against breast cancer may be through the suppression of in situ estrogen formation using aromatase inhibitors. A diet high in fruits and vegetables may reduce the incidence of breast cancer, because they contain phytochemicals that can act as aromatase inhibitors. In our previous studies, we found that grapes and wine contain potent phytochemicals that can inhibit aromatase. We show that red wine was more effective than white wine in suppressing aromatase activity. Interestingly, our results from white wine studies suggest a weak inductive effect of alcohol on aromatase activity. On the other hand, the potent effect of anti-aromatase chemicals in red wine overcomes the weak inductive effect of alcohol in wine. Several purification procedures were performed on whole red wine to separate active aromatase inhibitors from non-active compounds. These techniques included liquid-liquid extraction, silica gel chromatography, various solid phase extraction (SPE) columns, and high performance liquid chromatography. An active Pinot Noir red wine SPE C18 column fraction (20% acetonitrile:water) was more effective than complete Pinot Noir wine in suppressing aromatase assay. This red wine extract was further analyzed in a transgenic mouse model in which aromatase was over-expressed in mammary tissue. Our gavaged red wine extract completely abrogated aromatase-induced hyperplasia and other neoplastic changes in mammary tissue. These results suggest that red wine or red wine extract may be a chemopreventive diet supplement for postmenopausal women who have a high risk of breast cancer. Further research is underway to purify and characterize the active compounds in red wine that are responsible for the inhibition of aromatase.",
"title": "Anti-aromatase chemicals in red wine."
},
{
"docid": "MED-1184",
"text": "It has been shown that feces of patients with ulcerative colitis uniformly contain sulfate reducing bacteria. Sulfide produced by these bacteria interferes with butyrate-dependent energy metabolism of cultured colonocytes and may be involved in the pathogenesis of ulcerative colitis. Mucosal biopsies from the sigmoid rectum of 10 patients (no caner, polyps, inflammatory bowel disease) were incubated with either NaCl, sodium hydrogen sulfide (1 mmol/L), a combination of both sodium hydrogen sulfide and butyrate (10 mmol/L), or butyrate. Mucosal proliferation was assessed by bromodeoxyuridine labeling of cells in S-phase. Compared to NaCl, sulfide increased the labeling of the entire crypt significantly, by 19% (p < 0.05). This effect was due to an expansion of the proliferative zone to the upper crypt (compartments 3-5), where the increase in proliferation was 54%. Sulfide-induced hyperproliferation was reversed when samples were coincubated with sulfide and butyrate. The study shows that sodium hydrogen sulfide induces mucosal hyperproliferation. Our data support a possible role of sulfide in the pathogenesis of UC and confirm the role of butyrate in the regulation of colonic proliferation and in the treatment of UC.",
"title": "Antagonistic effects of sulfide and butyrate on proliferation of colonic mucosa: a potential role for these agents in the pathogenesis of ulcerativ..."
},
{
"docid": "MED-4216",
"text": "High levels of insulin-like growth factor 1 (IGF-1) are associated with increased risk of prostate cancer, whereas increased levels of some of its binding proteins (IGFBPs) seem to be protective. High intakes of dietary protein, especially animal and soy protein, appear to increase IGF-1. However, soy isoflavones have demonstrated anti-proliferative and apoptotic effects both in vitro and in vivo. We evaluated dietary intakes of total protein and soy isoflavones in relation to the IGF axis in prostate cancer patients making comprehensive lifestyle changes including a very low-fat vegan diet supplemented with soy protein (58 g/day). After one year, intervention group patients reported significantly higher intakes of dietary protein and soy isoflavones compared to usual-care controls (P < 0.001). IGF-1 increased significantly in both groups, whereas IGFBP-1 rose in the experimental group only (P < 0.01). Increases in vegetable protein over one year were associated with increases in IGFBP-1 among intervention group patients (P < 0.05). These results suggest that dietary protein and soy isoflavones, in the context of comprehensive lifestyle changes, may not significantly alter IGF-1. However, given the recent literature indicating that high intake of protein rich in essential amino acids (animal or soy protein) may increase IGF-1, it may be prudent for men with early stage prostate cancer not to exceed dietary protein recommendations.",
"title": "Relationship of dietary protein and soy isoflavones to serum IGF-1 and IGF binding proteins in the Prostate Cancer Lifestyle Trial."
},
{
"docid": "MED-2943",
"text": "BACKGROUND: Western diets, which typically contain large amounts of energy-dense processed foods, together with a sedentary lifestyle are associated with increased cardiometabolic risk. We evaluated the long-term effects of consuming a low-calorie low-protein vegan diet or performing regular endurance exercise on cardiometabolic risk factors. METHODS: In this cross-sectional study, cardiometabolic risk factors were evaluated in 21 sedentary subjects, who had been on a low-calorie low-protein raw vegan diet for 4.4 +/- 2.8 years, (mean age, 53.1 +/- 11 yrs), 21 body mass index (BMI)-matched endurance runners consuming Western diets, and 21 age- and gender-matched sedentary subjects, consuming Western diets. RESULTS: BMI was lower in the low-calorie low-protein vegan diet (21.3 +/- 3.1 kg/m(2)) and endurance runner (21.1 +/- 1.6 kg/m(2)) groups than in the sedentary Western diet group (26.5 +/- 2.7 kg/m(2)) (p < 0.005). Plasma concentrations of lipids, lipoproteins, glucose, insulin, C-reactive protein, blood pressure (BP), and carotid artery intima-media thickness were lower in the low-calorie low-protein vegan diet and runner groups than in the Western diet group (all p < 0.05). Both systolic and diastolic BP were lower in the low-calorie low-protein vegan diet group (104 +/- 15 and 62 +/- 11 mm Hg) than in BMI-matched endurance runners (122 +/- 13 and 72 +/- 9 mmHg) and Western diet group (132 +/- 14 and 79 +/- 8 mm Hg) (p < 0.001); BP values were directly associated with sodium intake and inversely associated with potassium and fiber intake. CONCLUSIONS: Long-term consumption of a low-calorie low-protein vegan diet or regular endurance exercise training is associated with low cardiometabolic risk. Moreover, our data suggest that specific components of a low-calorie low-protein vegan diet provide additional beneficial effects on blood pressure.",
"title": "Long-term low-calorie low-protein vegan diet and endurance exercise are associated with low cardiometabolic risk."
},
{
"docid": "MED-1527",
"text": "Importance Some evidence suggests vegetarian dietary patterns may be associated with reduced mortality, but the relationship is not well established. Objective To evaluate the association between vegetarian dietary patterns and mortality. Design Prospective cohort study; mortality analysis by Cox proportional hazards regression, controlling for important demographic and lifestyle confounders. Setting Adventist Health Study 2 (AHS-2), a large North American cohort. Participants A total of 96 469 Seventh-day Adventist men and women recruited between 2002 and 2007, from which an analytic sample of 73 308 participants remained after exclusions. Exposures Diet was assessed at baseline by a quantitative food frequency questionnaire and categorized into 5 dietary patterns: nonvegetarian, semi-vegetarian, pesco-vegetarian, lacto-ovo–vegetarian, and vegan. Main Outcome and Measure The relationship between vegetarian dietary patterns and all-cause and cause-specific mortality; deaths through 2009 were identified from the National Death Index. Results There were 2570 deaths among 73 308 participants during a mean follow-up time of 5.79 years. The mortality rate was 6.05 (95% CI, 5.82–6.29) deaths per 1000 person-years. The adjusted hazard ratio (HR) for all-cause mortality in all vegetarians combined vs non-vegetarians was 0.88 (95% CI, 0.80–0.97). The adjusted HR for all-cause mortality in vegans was 0.85 (95% CI, 0.73–1.01); in lacto-ovo–vegetarians, 0.91 (95% CI, 0.82–1.00); in pesco-vegetarians, 0.81 (95% CI, 0.69–0.94); and in semi-vegetarians, 0.92 (95% CI, 0.75–1.13) compared with nonvegetarians. Significant associations with vegetarian diets were detected for cardiovascular mortality, noncardiovascular noncancer mortality, renal mortality, and endocrine mortality. Associations in men were larger and more often significant than were those in women. Conclusions and Relevance Vegetarian diets are associated with lower all-cause mortality and with some reductions in cause-specific mortality. Results appeared to be more robust in males. These favorable associations should be considered carefully by those offering dietary guidance.",
"title": "Vegetarian Dietary Patterns and Mortality in Adventist Health Study 2"
},
{
"docid": "MED-2579",
"text": "There are now extensive scientific data suggesting the potential role of dietary and non-dietary phytochemicals in the prevention and control of prostate cancer (PCA) growth and progression. PCA is a disease of elderly male populations with a relatively slower rate of growth and progression as compared to most other cancers and, therefore, is a candidate disease for preventive intervention. Overall, PCA growth and progression involve aberrant mitogenic and survival signaling and deregulated cell cycle progression, accompanied by gradual accumulation of genetic and epigenetic changes over a period of years. Several mechanisms, including overexpression of growth, survival and angiogenic factors and their receptors, together with a loss/decrease of tumor suppressor p53, retinoblastoma and cyclin-dependent kinase inhibitor, have been implicated in PCA growth and progression. Therefore, phytochemicals targeting these molecular events could have a promising role in PCA prevention and/or therapy. Inositol hexaphosphate (IP6) is a major constituent of most cereals, legumes, nuts, oil seeds and soybean. Taken orally as an over-the-counter dietary/nutrient supplement, and is recognised as offering several health benefits without any known toxicity. In vitro anticancer efficacy of IP6 has been observed in many human, mouse and rat prostate cancer cells. Completed studies also show that oral feeding of IP6 inhibits human PCA xenograft growth in nude mice without toxicity. In a recently completed pilot study, we observed similar preventive effects of IP6 on prostate tumorigenesis in the TRAMP model. Mechanistic studies indicate that IP6 targets mitogenic and survival signaling, as well as cell cycle progression, in PCA cells. IP6 is also shown to target molecular events associated with angiogenesis. Moreover, IP6 has pleiotropic molecular targets for its overall efficacy against PCA and, therefore, could be a suitable candidate agent for preventive intervention of this malignancy in humans.",
"title": "Prostate cancer and inositol hexaphosphate: efficacy and mechanisms."
},
{
"docid": "MED-1417",
"text": "Background: Epidemiologic studies have suggested that most cases of sporadic colon cancer can be attributed to diet. The recognition that colonic microbiota have a major influence on colonic health suggests that they might mediate colonic carcinogenesis. Objective: To examine the hypothesis that the influence of diet on colon cancer risk is mediated by the microbiota through their metabolites, we measured differences in colonic microbes and their metabolites in African Americans with a high risk and in rural native Africans with a low risk of colon cancer. Design: Fresh fecal samples were collected from 12 healthy African Americans aged 50–65 y and from 12 age- and sex-matched native Africans. Microbiomes were analyzed with 16S ribosomal RNA gene pyrosequencing together with quantitative polymerase chain reaction of the major fermentative, butyrate-producing, and bile acid–deconjugating bacteria. Fecal short-chain fatty acids were measured by gas chromatography and bile acids by liquid chromatography–mass spectrometry. Results: Microbial composition was fundamentally different, with a predominance of Prevotella in native Africans (enterotype 2) and of Bacteroides in African Americans (enterotype 1). Total bacteria and major butyrate-producing groups were significantly more abundant in fecal samples from native Africans. Microbial genes encoding for secondary bile acid production were more abundant in African Americans, whereas those encoding for methanogenesis and hydrogen sulfide production were higher in native Africans. Fecal secondary bile acid concentrations were higher in African Americans, whereas short-chain fatty acids were higher in native Africans. Conclusion: Our results support the hypothesis that colon cancer risk is influenced by the balance between microbial production of health-promoting metabolites such as butyrate and potentially carcinogenic metabolites such as secondary bile acids.",
"title": "Diet, microbiota, and microbial metabolites in colon cancer risk in rural Africans and African Americans"
},
{
"docid": "MED-2182",
"text": "Over the past century, a major shift in North American food practices has been taking place. However, the literature on this topic is lacking in several areas. Some available research on food and cooking practices in the current context is presented, with a focus on how these are affecting health and how they might be contributing to health inequalities within the population. First, cooking and cooking skills are examined, along with the ambiguities related to terms associated with cooking in the research literature. Food choice, cooking, and health are described, particularly in relation to economic factors that may lead to health inequalities within the population. The importance of developing an understanding of factors within the wider food system as part of food choice and cooking skills is presented, and gaps in the research literature are examined and areas for future research are presented. Cooking practices are not well studied but are important to an understanding of human nutritional health as it relates to cultural, environmental, and economic factors.",
"title": "Food, cooking skills, and health: a literature review."
},
{
"docid": "MED-2370",
"text": "In this third installment of the series, we point out that the absence of an explicit, detailed and plausible hypothesis linking hypercholesterolemia to the events in the artery wall was probably an important reason for continuing skepticism and for failure to treat elevated blood cholesterol levels. The rapid advances in understanding of lipoprotein metabolism in the 1950s and 1960s and the application of modern cellular biology in the 1970s provided the context for a modern consensus on pathogenetic mechanisms of atherogenesis.",
"title": "Thematic review series: the pathogenesis of atherosclerosis: an interpretive history of the cholesterol controversy, part III: mechanistically defi..."
},
{
"docid": "MED-4475",
"text": "The deleterious effects of tumor-promoting tobacco carcinogen, nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK, nicotine-derived nitrosamine ketone) have undoubtedly been stipulated. Though many tobacco agents play a part in the development of lung tumors, the potent effects of NNK remain unmatched. It is therefore critical to distinguish the variety of cofactors involved in NNK-mediated pathogenesis, and the unique pathways necessary for successful cellular biotransformation. Current reviews have consistently identified the strengths of NNK and prospective tumor capabilities. Others have delineated specific cellular factors mediating NNK and lung tumors, and have identified metabolic and signaling pathways largely responsible for NNK activation and tumorigenic initiation. Unique to this review is that it summarizes the extensive network of cofactors and cellular mechanisms that promote NNK-specific lung tumorigenesis. As such, it displays a fuller, more comprehensive overview, bringing us one step closer to understanding the fatal consequences of NNK, thus, discovering new avenues that successfully break the cycle of NNK-mediated lung carcinogenesis.",
"title": "Understanding tobacco smoke carcinogen NNK and lung tumorigenesis."
},
{
"docid": "MED-3001",
"text": "Over the last three decades, the concept of Western disease has become well established. Medicine has approached this group of diseases by searching for new cures but has achieved relatively little success. We argue that medicine should now accept the failure of this strategy and place a major emphasis on prevention. The key objective is to change the climate of opinion so that prevention is taken seriously by the general population. The chief activity should be a wide ranging public education campaign so as to persuade people to live a healthier lifestyle. Medicine will require restructuring in order to carry out this work. Medical education needs to be reformed so that medical students receive the necessary training. This must be done as part of an integrated approach in which government, industry and medical research all play a major role. Governments should use taxation and subsidies in areas such as food and tobacco so as to shift consumption patterns towards healthier products. Governments must also tighten laws on tobacco sales and advertising, support health education, and improve food labelling. Industry must be made far more responsive to the health needs of the population. This should be done both by public education, so as to alter demand, and by government action. Medical research should change its emphasis from studying the detailed mechanisms of disease (\"complex research\") to studying the role of lifestyle factors (\"simple research\").",
"title": "Towards a new system of health: the challenge of Western disease."
},
{
"docid": "MED-1528",
"text": "A vegetarian diet generally includes plenty of vegetables and fruits, which are rich in phytochemicals, antioxidants, fiber, magnesium, vitamins C and E, Fe³⁺, folic acid and n-6 polyunsaturated fatty acid (PUFA), and is low in cholesterol, total fat and saturated fatty acid, sodium, Fe²⁺, zinc, vitamin A, B₁₂ and D, and especially n-3 PUFA. Mortality from all-cause, ischemic heart disease, and circulatory and cerebrovascular diseases was significantly lower in vegetarians than in omnivorous populations. Compared with omnivores, the incidence of cancer and type 2 diabetes was also significantly lower in vegetarians. However, vegetarians have a number of increased risk factors for non-communicable diseases such as increased plasma homocysteine, mean platelet volume and platelet aggregability compared with omnivores, which are associated with low intake of vitamin B₁₂ and n-3 PUFA. Based on the present data, it would seem appropriate for vegetarians to carefully design their diet, specifically focusing on increasing their intake of vitamin B₁₂ and n-3 PUFA to further reduce already low mortality and morbidity from non-communicable diseases. © 2013 Society of Chemical Industry.",
"title": "Effect of the vegetarian diet on non-communicable diseases."
},
{
"docid": "MED-3446",
"text": "Seaweed and soy foods are consumed daily in Japan, where breast cancer rates for postmenopausal women are significantly lower than in the West. Likely mechanisms include differences in diet, especially soy consumption, and estrogen metabolism. Fifteen healthy postmenopausal women participated in this double-blind trial of seaweed supplementation with soy challenge. Participants were randomized to 7 wk of either 5 g/d seaweed (Alaria) or placebo (maltodextrin). During wk 7, participants also consumed a daily soy protein isolate (2 mg isoflavones/kg body weight). After a 3-wk washout period, participants were crossed over to the alternate supplement schedule. There was an inverse correlation between seaweed dose (mg/kg body weight) and serum estradiol (E2) (seaweed-placebo = y = -2.29 x dose + 172.3; r = -0.70; P = 0.003), [corrected] which was linear across the range of weights. Soy supplementation increased urinary daidzein, glycitein, genistein, and O-desmethylangolensin (P = 0.0001) and decreased matairesinol and enterolactone (P < 0.05). Soy and seaweed plus soy (SeaSoy) increased urinary excretion of 2-hydroxyestrogen (2-OHE) (P = 0.0001) and the ratio of 2-OHE:16alpha-hydroxyestrone (16alphaOHE(1)) (P = 0.01). For the 5 equol excretors, soy increased urinary equol excretion (P = 0.0001); the combination of SeaSoy further increased equol excretion by 58% (P = 0.0001). Equol producers also had a 315% increase in 2:16 ratio (P = 0.001) with SeaSoy. Seaweed favorably alters estrogen and phytoestrogen metabolism and these changes likely include modulation of colonic bacteria.",
"title": "Dietary seaweed modifies estrogen and phytoestrogen metabolism in healthy postmenopausal women."
},
{
"docid": "MED-3797",
"text": "A double blind crossover trial of the prolactin inhibitor bromocriptine in painful benign breast disease is reported. Twenty-nine women with cyclical mastalgia and 11 with non-cyclical pain were treated with bromocriptine, 5 mg daily, and placebo over six menstrual cycels. Assessment of response to treatment was made by a linear analogue system and clinical examination together with plasma prolactin estimations. Bromocriptine produced a significant improvement in breast symptoms and a significant fall in prolactin levels in the cyclical pain group, but had no effect in the non-cyclical group. These results suggest that bromocriptine offers a new and effective approach in the management of cyclical breast pain.",
"title": "A double blind trial of the prolactin inhibitor bromocriptine in painful benign breast disease."
},
{
"docid": "MED-2803",
"text": "Osteoarthritis is a condition caused in part by injury, loss of cartilage structure and function, and an imbalance in inflammatory and anti-inflammatory pathways. It primarily affects the articular cartilage and subchondral bone of synovial joints and results in joint failure, leading to pain upon weight bearing including walking and standing. There is no cure for osteoarthritis, as it is very difficult to restore the cartilage once it is destroyed. The goals of treatment are to relieve pain, maintain or improve joint mobility, increase the strength of the joints and minimize the disabling effects of the disease. Recent studies have shown an association between dietary polyphenols and the prevention of osteoarthritis-related musculoskeletal inflammation. This review discusses the effects of commonly consumed polyphenols, including curcumin, epigallocatechin gallate and green tea extract, resveratrol, nobiletin and citrus fruits, pomegranate, as well as genistein and soy protein, on osteoarthritis with an emphasis on molecular antiosteoarthritic mechanisms. Copyright © 2012 Elsevier Inc. All rights reserved.",
"title": "Dietary polyphenols and mechanisms of osteoarthritis."
},
{
"docid": "MED-1531",
"text": "Observational and ecological studies are generally used to determine the presence of effect of cancer risk-modifying factors. Researchers generally agree that environmental factors such as smoking, alcohol consumption, poor diet, lack of physical activity, and low serum 25-hdyroxyvitamin D levels are important cancer risk factors. This ecological study used age-adjusted incidence rates for 21 cancers for 157 countries (87 with high-quality data) in 2008 with respect to dietary supply and other factors, including per capita gross domestic product, life expectancy, lung cancer incidence rate (an index for smoking), and latitude (an index for solar ultraviolet-B doses). The factors found to correlate strongly with multiple types of cancer were lung cancer (direct correlation with 12 types of cancer), energy derived from animal products (direct correlation with 12 types of cancer, inverse with two), latitude (direct correlation with six types, inverse correlation with three), and per capita gross national product (five types). Life expectancy and sweeteners directly correlated with three cancers, animal fat with two, and alcohol with one. Consumption of animal products correlated with cancer incidence with a lag time of 15–25 years. Types of cancer which correlated strongly with animal product consumption, tended to correlate weakly with latitude; this occurred for 11 cancers for the entire set of countries. Regression results were somewhat different for the 87 high-quality country data set and the 157-country set. Single-country ecological studies have inversely correlated nearly all of these cancers with solar ultraviolet-B doses. These results can provide guidance for prevention of cancer.",
"title": "A Multicountry Ecological Study of Cancer Incidence Rates in 2008 with Respect to Various Risk-Modifying Factors"
},
{
"docid": "MED-1949",
"text": "The first infants to experience modern pre- and neonatal care are now in their thirties, an age at which the incidence of cardiometabolic disease is low. However, data from cohorts born preterm prior to the introduction of modern care suggest an increased risk of type 2 diabetes. For young adult cohorts of former very small or very preterm infants, there is accumulating evidence of increased risk factors for later cardiovascular disease, including higher blood pressure, lower lean body mass, impaired glucose regulation, and perhaps a more atherogenic lipid profile. Regarding lifestyle, adults born very small or very preterm undertake less non-conditioning physical activity and may have a lower intake of fruit and milk products. Any intervention reducing risk factors, in particular blood pressure and low physical activity, would have a substantial potential to reduce the lifetime disease burden in small preterm infants. There are now enough data to warrant an expert evaluation of the level of evidence for cardiometabolic disease in individuals born very small or very preterm, which has possible public health implications. Copyright © 2013 Elsevier Ltd. All rights reserved.",
"title": "Is very preterm birth a risk factor for adult cardiometabolic disease?"
},
{
"docid": "MED-1213",
"text": "Background The American Heart Association’s 2020 Strategic Impact Goals target a 20% relative improvement in overall cardiovascular health with the use of 4 health behavior (smoking, diet, physical activity, body mass) and 3 health factor (plasma glucose, cholesterol, blood pressure) metrics. We sought to define current trends and forward projections to 2020 in cardiovascular health. Methods and Results We included 35 059 cardiovascular disease–free adults (aged ≥20 years) from the National Health and Nutrition Examination Survey 1988–1994 and subsequent 2-year cycles during 1999–2008. We calculated population prevalence of poor, intermediate, and ideal health behaviors and factors and also computed a composite, individual-level Cardiovascular Health Score for all 7 metrics (poor=0 points; intermediate=1 point; ideal=2 points; total range, 0–14 points). Prevalence of current and former smoking, hypercholesterolemia, and hypertension declined, whereas prevalence of obesity and dysglycemia increased through 2008. Physical activity levels and low diet quality scores changed minimally. Projections to 2020 suggest that obesity and impaired fasting glucose/diabetes mellitus could increase to affect 43% and 77% of US men and 42% and 53% of US women, respectively. Overall, population-level cardiovascular health is projected to improve by 6% overall by 2020 if current trends continue. Individual-level Cardiovascular Health Score projections to 2020 (men=7.4 [95% confidence interval, 5.7–9.1]; women=8.8 [95% confidence interval, 7.6–9.9]) fall well below the level needed to achieve a 20% improvement (men=9.4; women=10.1). Conclusions The American Heart Association 2020 target of improving cardiovascular health by 20% by 2020 will not be reached if current trends continue.",
"title": "Cardiovascular Health Behavior and Health Factor Changes (1988 –2008) and Projections to 2020"
},
{
"docid": "MED-2183",
"text": "Objective Cooking programs are growing in popularity; however an extensive review has not examined overall impact. Therefore, this study reviewed previous research on cooking/home food preparation interventions and diet and health-related outcomes among adults and identified implications for practice and research. Design Literature review and descriptive summative method. Main outcome measures Dietary intake, knowledge/skills, cooking attitudes and self-efficacy/confidence, health outcomes. Analysis Articles evaluating effectiveness of interventions that included cooking/home food preparation as the primary aim (January 1980 through December 2011) were identified via OVID MEDLINE, Agricola and Web of Science databases. Studies grouped according to design and outcomes were reviewed for validity using an established coding system. Results were summarized for several outcome categories. Results Of 28 studies identified, 12 included a control group with six as non-randomized and six as randomized controlled trials. Evaluation was done post-intervention for five studies, pre- and post-intervention for 23 and beyond post-intervention for 15. Qualitative and quantitative measures suggested a positive influence on main outcomes. However, non-rigorous study designs, varying study populations, and use of non-validated assessment tools limited stronger conclusions. Conclusions and Implications Well-designed studies are needed that rigorously evaluate long-term impact on cooking behavior, dietary intake, obesity and other health outcomes.",
"title": "Impact of cooking and home food preparation interventions among adults: outcomes and implications for future programs"
},
{
"docid": "MED-2092",
"text": "Objectives To determine the cytotoxicity of three commercial mouthrinses Klorhex, Andorex and Tanflex on buccal epithelial cells using micronucleus (MN) test. Materials and Methods 28 patients with aged 16–24 undergone three mouthrinses’ application were analyzed before and after one week exposure. Physiologic saline was used for the control group. The MN incidence was scored in the buccal epithelial of each participants. The difference in pre- and post-treatment after one week incidence of MN and plaque (PI) and gingival indices (GI) was compared by non-parametric statistical tests. Results The micronuclei incidence increased in Klorhex, Tanflex and Andorex groups after exposure to mouth rinses (P<.05). But when compared with the control group, there was not any difference between Andorex and control group (P>.05). In the other study groups, MN incidence was significantly increased after 7 days treatment (P<.05). GI scores of all groups were decreased significantly (P<.05). PI scores were decreased only in the Klorhex group (P<.05). Conclusions Our primary findings support the presence of possible cytotoxic effects of the mouthrinses on gingival epithelial cells.",
"title": "Cytotoxicity of Mouthrinses on Epithelial Cells by Micronucleus Test"
},
{
"docid": "MED-2765",
"text": "To prevent or delay the occurrence of chronic diseases, scientific bodies from the cardiologic and oncologic disciplines have made recommendations regarding the daily dietary intake of certain macro- and micronutrients. This study assessed the knowledge of a random population of 2,305 individuals comprising members of the public, health care workers, university graduate students, and health club attendees. Segments of this population might be expected to have a greater understanding and ability to implement these dietary recommendations. We found that over 90% of the participants were unaware of the recommendations for calcium, salt, vitamin A, and fiber, and the fiber content in a high fiber cereal. Approximately 80% of the participants were unaware of the recommendations regarding fat intake and could not calculate the fat content of a food product. Almost half of the study population took a vitamin pill daily. Of the subjects who were aware of the correct unit measurement for vitamin A (IU), almost 25% of gave a response that exceeded the recommended daily intake. A majority of this study population were unaware of the dietary recommendations regarding the prevention of cardiovascular events and cancer. Subgroups of this study population that might be expected to have more information regarding these recommendations (i.e., having higher education or being a health care professional) did not display a satisfactory level of knowledge. To further compound the problems of adhering to the recommended guidelines, the labeling of many food products is misleading. The recommendations on dietary intake and the information on food product content must be transmitted to the public in a form that allows for ready application when purchasing and consuming food.",
"title": "The value of current nutrition information."
},
{
"docid": "MED-4635",
"text": "The increased flow of goods, people, and ideas associated with globalization have contributed to an increase in noncommunicable diseases in much of the world. One response has been to encourage lifestyle changes with educational programmes, thus controlling the lifestyle-related disease. Key assumptions with this approach are that people's food preferences are linked to their consumption patterns, and that consumption patterns can be transformed through educational initiatives. To investigate these assumptions, and policies that derive from it, we undertook a broad-based survey of food-related issues in the Kingdom of Tonga using a questionnaire. Data on the relationships between food preferences, perception of nutritional value, and frequency of consumption were gathered for both traditional and imported foods. The results show that the consumption of health-compromising imported foods was unrelated either to food preferences or to perceptions of nutritional value, and suggests that diet-related diseases may not be amenable to interventions based on education campaigns. Given recent initiatives towards trade liberalization and the creation of the World Trade Organization, tariffs or import bans may not serve as alternative measures to control consumption. This presents significant challenges to health policy-makers serving economically marginal populations and suggests that some population health concerns cannot be adequately addressed without awareness of the effects of global trade.",
"title": "Globalization, diet, and health: an example from Tonga."
},
{
"docid": "MED-1865",
"text": "In vitro studies show Hibiscus sabdariffa L., an ingredient found in many herbal tea blends and other beverages, has antioxidant properties, and, in animal models, extracts of its calyces have demonstrated hypocholesterolemic and antihypertensive properties. Our objective in this study was to examine the antihypertensive effects of H. sabdariffa tisane (hibiscus tea) consumption in humans. A randomized, double-blind, placebo-controlled clinical trial was conducted in 65 pre- and mildly hypertensive adults, age 30-70 y, not taking blood pressure (BP)-lowering medications, with either 3 240-mL servings/d of brewed hibiscus tea or placebo beverage for 6 wk. A standardized method was used to measure BP at baseline and weekly intervals. At 6 wk, hibiscus tea lowered systolic BP (SBP) compared with placebo (-7.2 +/- 11.4 vs. -1.3 +/- 10.0 mm Hg; P = 0.030). Diastolic BP was also lower, although this change did not differ from placebo (-3.1 +/- 7.0 vs. -0.5 +/- 7.5 mm Hg; P = 0.160). The change in mean arterial pressure was of borderline significance compared with placebo (-4.5 +/- 7.7 vs. -0.8 +/- 7.4 mm Hg; P = 0.054). Participants with higher SBP at baseline showed a greater response to hibiscus treatment (r = -0.421 for SBP change; P = 0.010). No effects were observed with regard to age, gender, or dietary supplement use. These results suggest daily consumption of hibiscus tea, in an amount readily incorporated into the diet, lowers BP in pre- and mildly hypertensive adults and may prove an effective component of the dietary changes recommended for people with these conditions.",
"title": "Hibiscus sabdariffa L. tea (tisane) lowers blood pressure in prehypertensive and mildly hypertensive adults."
},
{
"docid": "MED-2941",
"text": "Several cohort studies have examined the association of carotid intima-media thickness (IMT) with the risk of stroke or myocardial infarction in apparently healthy persons. We investigated the predictive value of IMT of cardiovascular mortality in elderly community-dwelling people, beyond the prediction provided by age and MMSE. assessed by means of a multivariate Cox model. Carotid IMT and plaque were evaluated bilaterally with ultrasonography in 298 people older than 75 years ( 120 men and 178 women, average age: 79.6 years). The LILAC study started on July 25, 2000. Consultations were repeated every year. The follow-up ended on November 30, 2004. During the mean follow-up span of 1152 days, 30 subjects (21 men and nine women) died. Nine deaths were attributable to cardiovascular causes Imyocardial infarction: two men and three women; stroke: two men and two women). The age- and MMSE-adjusted relative risk (RR) and 95% confidence interval (95% CI) of developing all-cause mortality was assessed. A 0.3 mm increase in left IMT was associated with a RR of predicted 1.647 (1.075-2.524), and a similar increase in right IMT with a RR of 3.327 (1.429-7.746). For cardiovascular mortality, the corresponding RR values were 2.351 (1.029-5.372) and 2.890 (1.059-7.891), respectively. Carotid IMT assessed by ultrasonography is positively associated with an increased risk of all-cause and cardiovascular death in elderly community-dwelling people.",
"title": "Common carotid intima-media thickness is predictive of all-cause and cardiovascular mortality in elderly community-dwelling people: Longitudinal Investigation for the Longevity and Aging in Hokkaido County (LILAC) study"
},
{
"docid": "MED-2296",
"text": "This study aimed to investigate health belief as a major motive for diet and lifestyle behaviors of 100 vegans in the United States; and to determine congruence with selected health and nutrition outcomes. Response data from an administered questionnaire was analyzed. Statistical analyses determined the most common factors influencing diet choice; the number of vegans practicing particular lifestyle behaviors; body mass index; and prevalence of self-reported chronic disease diagnoses. Nutrient intakes were analyzed and assessed against Dietary Reference Intakes. Health was the most reported reason for diet choice (47%). In the health belief, animal welfare, and religious/other motive categories, low percentages of chronic disease diagnoses were reported: 27%, 11%, and 15%, respectively. There were no significant differences in health behaviors and indices among vegan motive categories, except for product fat content choices. Within the entire study population, health-related vegan motive coincided with regular exercise; 71% normal BMI (mean=22.6); minimal alcohol and smoking practices; frequently consumed vegetables, nuts, and grains; healthy choices in meal types, cooking methods, and low-fat product consumption; and adequate intakes for most protective nutrients when compared to reference values. But incongruence was found with 0% intake adequacy for vitamin D; and observation of excessive sodium use. Copyright © 2013 Elsevier Ltd. All rights reserved.",
"title": "Vegan lifestyle behaviors: an exploration of congruence with health-related beliefs and assessed health indices."
},
{
"docid": "MED-1500",
"text": "BACKGROUND: Regular consumption of fruit and vegetables has been considered to be associated with a reduced risk of dementia and age-associated cognitive decline, although the association is currently unsupported by a systematic review of the literature. METHODS: We searched Medline, Embase, Biosis, ALOIS, the Cochrane library, different publisher databases as well as bibliographies of retrieved articles. All cohort studies with a follow-up of 6 months or longer were included if they reported an association of Alzheimer's disease or cognitive decline in regard to the frequency of fruit and vegetables consumption. FINDINGS: Nine studies with a total of 44,004 participants met the inclusion criteria. Six studies analyzed fruit and vegetables separately and five of them found that higher consumption of vegetables, but not fruit is associated with a decreased risk of dementia or cognitive decline. The same association was found by three further studies for fruit and vegetable consumption analytically combined. CONCLUSION: Increased intake of vegetables is associated with a lower risk of dementia and slower rates of cognitive decline in older age. Yet, evidence that this association is also valid for high fruit consumption is lacking.",
"title": "Fruit, vegetables and prevention of cognitive decline or dementia: a systematic review of cohort studies."
},
{
"docid": "MED-1416",
"text": "Mean faecal urobilinogen levels and the pH of stools were both found to be higher in subjects from a population group at high risk of developing cancer of the colon than in subjects matched for age, sex and socioeconomic status from a low-risk population group. An alkaline reaction of the colon contents seems to have a tumorigenic effect by a direct action on the mucus of the mucous cells. An acidic reaction, on the other hand, appears to be protective. These differences are dependent on the patterns of diet and manner of eating. Proper mastication of food, roughage, cellulose and vegetable fibre, and short-chain fatty acids of milk and fermented milk products in the diet appear to be protective.",
"title": "Faecal urobilinogen levels and pH of stools in population groups with different incidence of cancer of the colon, and their possible role in its aetiology."
},
{
"docid": "MED-2577",
"text": "A case-control study probing the role of diet on the incidence of colorectal cancer was undertaken in Athens, Greece, in a population characterized by ethnic homogeneity but substantial heterogeneity with respect to dietary habits. The case series consisted of 100 consecutive patients with histologically confirmed colorectal cancer admitted to two large hospitals of Athens during a 16-month period; the control series consisted of orthopaedic patients, admitted to the same hospitals during the same time period, individually matched to the index cases by age and sex. Dietary histories concerning the frequency of consumption (per month or per week) of about 80 food items were obtained by the same interviewer. Cases reported significantly less frequent consumption of vegetables (particularly beets, spinach, lettuce and cabbage) and, independently, significantly more frequent consumption of meat (notably lamb and beef). Between the two extremes (high-vegetable, low-meat diet versus high-meat, low-vegetable diet) a risk ratio of about 8 appears to exist, sufficient (in size and direction) to explain a substantial part of the international variation in the incidence of colorectal cancer. Significant associations were not found with beer or other alcoholic beverages, and significant interactions were not noted with respect to age, sex and anatomic localization (colon vs. rectum).",
"title": "Diet and colorectal cancer: a case-control study in Greece."
},
{
"docid": "MED-3216",
"text": "Increasing dietary protein results in an increase in urinary calcium. Despite over 80 y of research, the source of the additional urinary calcium remains unclear. Because most calcium balance studies found little effect of dietary protein on intestinal calcium absorption, it was assumed that the skeleton was the source of the calcium. The hypothesis was that the high endogenous acid load generated by a protein-rich diet would increase bone resorption and skeletal fracture. However, there are no definitive nutrition intervention studies that show a detrimental effect of a high protein diet on the skeleton and the hypothesis remains unproven. Recent studies from our laboratory demonstrate that dietary protein affects intestinal calcium absorption. We conducted a series of short-term nutrition intervention trials in healthy adults where dietary protein was adjusted to either low, medium or high. The highest protein diet resulted in hypercalciuria with no change in serum parathyroid hormone. Surprisingly, within 4 d, the low protein diet induced secondary hyperparathyroidism that persisted for 2 wk. The secondary hyperparathyroidism induced by the low protein diet was attributed to a reduction in intestinal calcium absorption (as assessed by dual stable calcium isotopes). The long-term consequences of these low protein-induced changes in calcium metabolism are not known, but they could be detrimental to skeletal health. Several recent epidemiological studies demonstrate reduced bone density and increased rates of bone loss in individuals habitually consuming low protein diets. Therefore, studies are needed to determine whether low protein intakes directly affect rates of bone resorption, bone formation or both.",
"title": "Low protein intake: the impact on calcium and bone homeostasis in humans."
},
{
"docid": "MED-3236",
"text": "A first objective of the present study was to estimate the acid-base balance of the food intake in vegetarians and non-vegetarians. A second objective was to evaluate if additional input of specific food items on the existing potential renal acid load (PRAL) list was necessary for the comparison of the two dietary patterns. Thirty vegetarians between the age of 18 and 30 years were matched for sex, age and BMI with 30 non-vegetarians. Based on the 3-days food diaries the acid-base status of the food intake was estimated using the PRAL method. Mean PRAL values as estimated with the standard table yielded an alkaline load of -5.4 +/- 14.4 mEq/d in the vegetarians compared to an acid load of 10.3 +/- 14.4 mEq/d in the nonvegetarians (p<0.001). Mean PRAL values as estimated with the extended table yielded an alkaline load of -10.9 +/-19.7 mEq/d in the vegetarians compared to an acid load of 13.8 +/- 17.1 mEq/d for the non-vegetarians (p<0.001). The findings of this study indicate that vegetarian food intake produces more alkaline outcomes compared to non-vegetarian diets. The use of the standard PRAL table was sufficient for discrimination between the two diets.",
"title": "Nutrient based estimation of acid-base balance in vegetarians and non-vegetarians."
},
{
"docid": "MED-1661",
"text": "Using data from 16 published reports, the authors correlated macroscopic disc degeneration grades with age, sex, and spine level in 600 lumbar intervertebral discs from 273 cadavers (ages: 0-96 years). Male discs were more degenerated than female discs at most ages; significantly so in the second, fifth, sixth, and seventh decades. On average, L4-L5 and L3-L4 level discs showed more degeneration than discs at other lumbar levels. These macroscopic findings corroborate radiographic data from epidemiologic studies. The calculations suggest that higher mechanical stress, perhaps combined with longer nutritional pathways, may be responsible for the earlier degeneration of male discs.",
"title": "Lumbar disc degeneration: correlation with age, sex, and spine level in 600 autopsy specimens."
},
{
"docid": "MED-2942",
"text": "BACKGROUND: There are no long-term prospective studies assessing the impact of the vegan diet on vitamin B-12 (B-12) status. Many vegans take B-12 supplements irregularly or refuse to adopt them at all, considering them to be \"unnatural\" products. The use of B-12 fortified food may be an alternative. Therefore, we aimed to estimate the long-term effect of a vegan diet on serum B-12 concentrations in healthy omnivore adults, comparing the influence of natural products consumption and B-12 fortified food. MATERIAL AND METHODS: A five year prospective study was carried out comprising 20 omnivore healthy adult subjects, who moved to strict vegan diet for 5 years. Ten volunteers followed vegan diet based entirely on natural products, while the remaining ten subjects consumed food fortified in B-12. In all subjects serum vitamin B-12 concentration was determined before and 6, 12, 24 and 60 months after the implementation of the diet. RESULTS: A significant decrease (p < 0.0002) of serum B-12 concentrations in the whole studied group was noted after 60 months of vegan diet. However, observed changes were in fact limited to the subgroup consuming exclusively natural products (p < 0.0001). CONCLUSIONS: Transition from omnivore to vegan diet is associated with the risk of vitamin B-12 deficiency. B-12 fortified products might constitute a valuable alternative in vegans refusing to take vitamin supplements.",
"title": "The impact of vegan diet on B-12 status in healthy omnivores: five-year prospective study."
},
{
"docid": "MED-3227",
"text": "Although high-protein diets induce hypercalciuria in humans, the source of the additional urinary calcium remains unclear. One hypothesis is that the high endogenous acid load of a high-protein diet is partially buffered by bone, leading to increased skeletal resorption and hypercalciuria. We used dual stable calcium isotopes to quantify the effect of a high-protein diet on calcium kinetics in women. The study consisted of 2 wk of a lead-in, well-balanced diet followed by 10 d of an experimental diet containing either moderate (1.0 g/kg) or high (2.1 g/kg) protein. Thirteen healthy women received both levels of protein in random order. Intestinal calcium absorption increased during the high-protein diet in comparison with the moderate (26.2 +/- 1.9% vs. 18.5 +/- 1.6%, P < 0.0001, mean +/- sem) as did urinary calcium (5.23 +/- 0.37 vs. 3.57 +/- 0.35 mmol/d, P < 0.0001, mean +/- sem). The high-protein diet caused a significant reduction in the fraction of urinary calcium of bone origin and a nonsignificant trend toward a reduction in the rate of bone turnover. There were no protein-induced effects on net bone balance. These data directly demonstrate that, at least in the short term, high-protein diets are not detrimental to bone.",
"title": "The impact of dietary protein on calcium absorption and kinetic measures of bone turnover in women."
},
{
"docid": "MED-2237",
"text": "In India, lung cancer is one of the most common and lethal cancers, and tobacco smoking remains its most important etiologic factors. The objective of our study is to examine the effects of different tobacco consumption forms, including smoking and chewing, on lung cancer risk of men in southern India, especially to compare the effects of bidi smoking to cigarette smoking on lung carcinogenesis. We also evaluated the possible role of Indian alcohol beverages and non-Indian alcohol beverages on lung carcinogenesis. We conducted a case-control study in Chennai and Trivandrum. In total, 778 lung cancer cases and 3,430 controls, including 1,503 cancer controls and 1,927 healthy controls, were recruited. The effects of cigarette, bidi smoking, chewing and alcohol drinking on the risk of lung cancer were estimated from unconditional multivariate logistic regression. We also applied the generalized additive model (GAM) with locally-weighted running-line smoothers (loess) to find the most plausible curve for the dose-response relationship. The results from GAM suggest a plateau after 35 years of smoking or 10 cigarette-equivalent pack-years for both cigarette and bidi. The OR is 4.54 (95%CI=2.96-6.95) and 6.45 (95%CI=4.38-9.50) for more than 30 years of cigarette-only and bidi-only smoking, respectively, and 6.87 (95%CI=4.62-10.2) and 10.7 (95%CI=5.82-19.6) for more than 12 weighted cumulative cigarette-only and bidi-only consumption, respectively. The lung cancer risk of former cigarette smokers drops down more quickly after quitting smoking compared to former bidi smokers. There is no evidence for the effect of chewing and lung cancer risk nor clear evidence of an effect of overall alcohol drinking among never-smokers, although Indian alcohol drinking seemed to remain associated with lung cancer risk under limited power (OR=2.67, 95%CI=1.02-7.02). Bidi smoking seems to have a stronger carcinogenic effect than cigarette smoking: this difference holds no matter which aspect of smoking was considered. Copyright 2003 Wiley-Liss, Inc.",
"title": "Tobacco smoking and chewing, alcohol drinking and lung cancer risk among men in southern India."
},
{
"docid": "MED-2945",
"text": "BACKGROUND: To investigate whether the Chinese lacto-vegetarian diet has protective effects on metabolic and cardiovascular disease (CVD). METHODS: One hundred sixty-nine healthy Chinese lacto-vegetarians and 126 healthy omnivore men aged 21-76 years were enrolled. Anthropometric indexes, lipid profile, insulin sensitivity, pancreatic β cell function, and intima-media thickness (IMT) of carotid arteries were assessed and compared. Cardiovascular risk points and probability of developing CVD in 5-10 years in participants aged 24-55 years were calculated. RESULTS: Compared with omnivores, lacto-vegetarians had remarkably lower body mass index, systolic and diastolic blood pressure, and serum levels of triglyceride, total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, γ-glutamyl transferase, serum creatinine, uric acid, fasting blood glucose, as well as lower total cholesterol/high-density lipoprotein cholesterol ratio. Vegetarians also had higher homeostasis model assessment β cell function and insulin secretion index and thinner carotid IMT than the omnivores did. These results corresponded with lower cardiovascular risk points and probability of developing CVD in 5-10 years in vegetarians 24-55 years old. CONCLUSIONS: In healthy Chinese men, the lacto-vegetarian diet seems to exert protective effects on blood pressure, lipid profiles, and metabolic parameters and results in significantly lower carotid IMT. Lower CVD risks found in vegetarians also reflect the beneficial effect of the Chinese lacto-vegetarian diet.",
"title": "Chinese lacto-vegetarian diet exerts favorable effects on metabolic parameters, intima-media thickness, and cardiovascular risks in healthy men."
},
{
"docid": "MED-2947",
"text": "PURPOSE: To measure prospectively and directly both organ dose and effective dose (ED) for adult cardiac and pulmonary computed tomographic (CT) angiography by using current clinical protocols for 64-detector CT in an anthropomorphic female phantom and to estimate lifetime attributable risk of breast and lung cancer incidence on the basis of measured ED and organ dose. MATERIALS AND METHODS: Cardiac and pulmonary 64-detector CT angiography was performed by using current clinical protocols to evaluate the pulmonary veins (electrocardiographically [ECG] gated, 64 sections at 0.625-mm collimation, 120 kVp, 300 mA, 0.35-second tube rotation), native coronary arteries (ECG gated; 64 sections at 0.625 mm; 120 kVp; maximum current, 500-750 mA; minimum, 100-350 mA; 0.35-second tube rotation) and pulmonary embolus (64 sections at 1.25 mm, 140 kVp, 645 mA, 0.5-second tube rotation). Absorbed organ doses were measured by using an anthropomorphic female phantom and metal oxide semiconductor field effect transistor detectors. ED was calculated from measured organ doses and the dose-length product. RESULTS: ED for current adult cardiac and pulmonary 64-detector CT angiography protocols were 12.4-31.8 mSv. Overall, skin, breast, and esophagus and heart had the highest recorded absorbed organ doses. Relative risk for breast cancer incidence for girls and women was 1.004-1.042 for a single examination. Relative risk for lung cancer incidence for men and women was 1.005-1.076 from a single examination. CONCLUSION: EDs and organ doses from 64-detector CT are higher than those previously reported for adult cardiac and pulmonary CT angiography protocols. Risk for breast and lung cancer induction from these studies is greatest for the younger patient population. (c) RSNA, 2007.",
"title": "Radiation dose from contemporary cardiothoracic multidetector CT protocols with an anthropomorphic female phantom: implications for cancer induction."
},
{
"docid": "MED-3138",
"text": "Background Many consumers avoid eating beans because they believe legume consumption will cause excessive intestinal gas or flatulence. An increasing body of research and the 2010 Dietary Guidelines for Americans supports the benefits of a plant-based diet, and legumes specifically, in the reduction of chronic disease risks. The purpose of the current research was to investigate the perception of increased flatulence and gastrointestinal discomfort among participants who consumed a ½ cup of beans daily for 8 or 12 weeks. Methods Participants in three studies to test the effects of beans on heart disease biomarkers completed the same weekly questionnaire to assess gastrointestinal discomfort issues such as increased flatulence, stool changes, and bloating. Studies 1 and 2 were randomized crossover trials. Participants consumed ½ cup of pinto beans, black-eyed peas, and canned carrots as control (n = 17) in Study 1 for three randomized 8-week phases. For Study 2, participants ate ½ cup baked beans or canned carrots as control (n = 29) for two randomized 8-week phases. Study 3 was a parallel arm trial with 40 subjects receiving ½ cup pinto beans and 40 consuming a control soup for 12 weeks. Changes in the frequency of perceived flatulence, stool characteristics, and bloating were the primary outcome measures. Chi-square distributions were examined for the presence or absence of symptoms and demographic characteristics to determine differences by gender, age, body mass index (BMI), and bean type. Results Less than 50% reported increased flatulence from eating pinto or baked beans during the first week of each trial, but only 19% had a flatulence increase with black-eyed peas. A small percentage (3-11%) reported increased flatulence across the three studies even on control diets without flatulence-producing components. Conclusions People's concerns about excessive flatulence from eating beans may be exaggerated. Public health nutritionists should address the potential for gastrointestinal discomfort when increasing fiber intake from beans with clients. It is important to recognize there is individual variation in response to different bean types.",
"title": "Perceptions of flatulence from bean consumption among adults in 3 feeding studies"
},
{
"docid": "MED-2460",
"text": "BACKGROUND: Elevated oxidative stress and impaired antioxidant defences are increasingly recognised features of asthma. Carotenoids are potent dietary antioxidants that may protect against asthma by reducing oxidative damage. OBJECTIVES: This study aimed firstly, to characterise circulating and airway levels of carotenoids in asthma compared to healthy controls, in relation to dietary intake. Secondly, the study aimed to test whether airway lycopene defences can be improved using oral supplements. METHODS: Induced sputum and peripheral blood samples were collected from subjects with asthma (n = 15) and healthy controls (n = 16). Dietary carotenoid intakes were estimated using the 24-hour recall method and analysed using a modified version of the Foodworks 210 Nutrient Calculation Software. Another group of healthy controls (n = 9) were supplemented with 20 mg/day lycopene for 4 weeks. Carotenoids (beta-carotene, lycopene, alpha-carotene, beta-cryptoxanthin, lutein/zeaxanthin) were measured by HPLC. RESULTS: Despite similar dietary intake, whole blood levels of total carotenoids, lycopene, lutein, beta-cryptoxanthin, alpha-carotene and beta-carotene were significantly lower in asthma than controls. However, there were no differences in plasma or sputum carotenoid levels. Induced sputum carotenoid levels were significantly lower than plasma and whole blood levels, but correlated strongly with plasma levels (r = 0.798, p < 0.001). Although there were no overall increases in either plasma or sputum lycopene levels following supplementation, changes in airway lycopene levels correlated with changes in plasma levels (r = 0.908, p < 0.002). CONCLUSIONS: Whole blood, but not plasma or sputum, carotenoid levels are deficient in asthma. Plasma carotenoid levels reflect airway carotenoid levels and when plasma levels are improved using oral supplements this is reflected in the airways.",
"title": "Airway and circulating levels of carotenoids in asthma and healthy controls."
},
{
"docid": "MED-3140",
"text": "To identify protective dietary predictors amongst long-lived elderly people (N= 785), the \"Food Habits in Later Life \"(FHILL) study was undertaken among five cohorts in Japan, Sweden, Greece and Australia. Between 1988 and 1991, baseline data on food intakes were collected. There were 785 participants aged 70 and over that were followed up to seven years. Based on an alternative Cox Proportional Hazard model adjusted to age at enrollment (in 5-year intervals), gender and smoking, the legume food group showed 7-8% reduction in mortality hazard ratio for every 20g increase in daily intake with or without controlling for ethnicity (RR 0.92; 95% CI 0.85-0.99 and RR 0.93; 95% CI 0.87-0.99, respectively). Other food groups were not found to be consistently significant in predicting survival amongst the FHILL cohorts.",
"title": "Legumes: the most important dietary predictor of survival in older people of different ethnicities."
},
{
"docid": "MED-4299",
"text": "The evolution of the human diet over the past 10,000 years from a Paleolithic diet to our current modern pattern of intake has resulted in profound changes in feeding behavior. Shifts have occurred from diets high in fruits, vegetables, lean meats, and seafood to processed foods high in sodium and hydrogenated fats and low in fiber. These dietary changes have adversely affected dietary parameters known to be related to health, resulting in an increase in obesity and chronic disease, including cardiovascular disease (CVD), diabetes, and cancer. Some intervention trials using Paleolithic dietary patterns have shown promising results with favorable changes in CVD and diabetes risk factors. However, such benefits may be offset by disadvantages of the Paleolithic diet, which is low in vitamin D and calcium and high in fish potentially containing environmental toxins. More advantageous would be promotion of foods and food ingredients from our ancestral era that have been shown to possess health benefits in the form of functional foods. Many studies have investigated the health benefits of various functional food ingredients, including omega-3 fatty acids, polyphenols, fiber, and plant sterols. These bioactive compounds may help to prevent and reduce incidence of chronic diseases, which in turn could lead to health cost savings ranging from $2 to $3 billion per year as estimated by case studies using omega-3 and plant sterols as examples. Thus, public health benefits should result from promotion of the positive components of Paleolithic diets as functional foods.",
"title": "Evolution of the human diet: linking our ancestral diet to modern functional foods as a means of chronic disease prevention."
},
{
"docid": "MED-2371",
"text": "Background Limiting consumption of eggs, which are high in cholesterol, is generally recommended to reduce risk of cardiovascular disease. However, recent evidence suggests that dietary cholesterol has limited influence on serum cholesterol or cardiac risk. Objective To assess the effects of egg consumption on endothelial function and serum lipids in hyperlipidemic adults. Methods Randomized, placebo-controlled crossover trial of 40 hyperlipidemic adults (24 women, 16 men; average age = 59.9 ± 9.6 years; weight = 76.3 ± 21.8 kilograms; total cholesterol = 244 ± 24 mg/dL). In the acute phase, participants were randomly assigned to one of the two sequences of a single dose of three medium hardboiled eggs and a sausage/cheese breakfast sandwich. In the sustained phase, participants were then randomly assigned to one of the two sequences of two medium hardboiled eggs and 1/2 cup of egg substitute daily for six weeks. Each treatment assignment was separated by a four-week washout period. Outcome measures of interest were endothelial function measured as flow mediated dilatation (FMD) and lipid panel. Results Single dose egg consumption had no effects on endothelial function as compared to sausage/cheese (0.4 ± 1.9 vs. 0.4 ± 2.4%; p = 0.99). Daily consumption of egg substitute for 6 weeks significantly improved endothelial function as compared to egg (1.0 ± 1.2% vs. -0.1 ± 1.5%; p < 0.01) and lowered serum total cholesterol (-18 ± 18 vs. -5 ± 21 mg/dL; p < 0.01) and LDL (-14 ± 20 vs. -2 ± 19 mg/dL; p = 0.01). Study results (positive or negative) are expressed in terms of change relative to baseline. Conclusions Egg consumption was found to be non-detrimental to endothelial function and serum lipids in hyperlipidemic adults, while egg substitute consumption was beneficial.",
"title": "Daily egg consumption in hyperlipidemic adults - Effects on endothelial function and cardiovascular risk"
},
{
"docid": "MED-1413",
"text": "The human oro-gastrointestinal (GI) tract is a complex system, consisting of oral cavity, pharynx, oesophagus, stomach, small intestine, large intestine, rectum and anus, which all together with the accessory digestive organs constitute the digestive system. The function of the digestive system is to break down dietary constituents into small molecules and then absorb these for subsequent distribution throughout the body. Besides digestion and carbohydrate metabolism, the indigenous microbiota has an important influence on host physiological, nutritional and immunological processes, and commensal bacteria are able to modulate the expression of host genes that regulate diverse and fundamental physiological functions. The main external factors that can affect the composition of the microbial community in generally healthy adults include major dietary changes and antibiotic therapy. Changes in some selected bacterial groups have been observed due to controlled changes to the normal diet e.g. high-protein diet, high-fat diet, prebiotics, probiotics and polyphenols. More specifically, changes in the type and quantity of non-digestible carbohydrates in the human diet influence both the metabolic products formed in the lower regions of the GI tract and the bacterial populations detected in faeces. The interactions between dietary factors, gut microbiota and host metabolism are increasingly demonstrated to be important for maintaining homeostasis and health. Therefore the aim of this review is to summarise the effect of diet, and especially dietary interventions, on the human gut microbiota. Furthermore, the most important confounding factors (methodologies used and intrinsic human factors) in relation to gut microbiota analyses are elucidated.",
"title": "Human gut microbiota: does diet matter?"
},
{
"docid": "MED-1502",
"text": "Animal work over the last three decades has generated a convincing body of evidence that a Western diet - one high in saturated fat and refined carbohydrates (HFS diet) - can damage various brain systems. In this review we examine whether there is evidence for this in humans, using converging lines of evidence from neuropsychological, epidemiological and neuroimaging data. Using the animal research as the organizing principal, we examined evidence for dietary induced impairments in frontal, limbic and hippocampal systems, and with their associated functions in learning, memory, cognition and hedonics. Evidence for the role of HFS diet in attention deficit disorder and in neurodegenerative conditions was also examined. While human research data is still at an early stage, there is evidence of an association between HFS diet and impaired cognitive function. Based upon the animal data, and a growing understanding of how HFS diets can disrupt brain function, we further suggest that there is a causal link running from HFS diet to impaired brain function in humans, and that HFS diets also contribute to the development of neurodegenerative conditions. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.",
"title": "The longer-term impacts of Western diet on human cognition and the brain."
},
{
"docid": "MED-3233",
"text": "Our objective in this study was to determine the effects of a high-protein and high-potential renal acid load (PRAL) diet on calcium (Ca) absorption and retention and markers of bone metabolism. In a randomized crossover design, 16 postmenopausal women consumed 2 diets: 1 with low protein and low PRAL (LPLP; total protein: 61 g/d; PRAL: -48 mEq/d) and 1 with high protein and high PRAL (HPHP; total protein: 118 g/d; PRAL: 33 mEq/d) for 7 wk each separated by a 1-wk break. Ca absorption was measured by whole body scintillation counting of radio-labeled (47)Ca. Compared with the LPLP diet, the HPHP diet increased participants' serum IGF-I concentrations (P < 0.0001), decreased serum intact PTH concentrations (P < 0.001), and increased fractional (47)Ca absorption (mean ± pooled SD: 22.3 vs. 26.5 ± 5.4%; P < 0.05) and urinary Ca excretion (156 vs. 203 ± 63 mg/d; P = 0.005). The net difference between the amount of Ca absorbed and excreted in urine did not differ between 2 diet periods (55 vs. 28 ± 51 mg/d). The dietary treatments did not affect other markers of bone metabolism. In summary, a diet high in protein and PRAL increases the fractional absorption of dietary Ca, which partially compensates for increased urinary Ca, in postmenopausal women. The increased IGF-I and decreased PTH concentrations in serum, with no change in biomarkers of bone resorption or formation, indicate a high-protein diet has no adverse effects on bone health.",
"title": "A diet high in meat protein and potential renal acid load increases fractional calcium absorption and urinary calcium excretion without affecting m..."
},
{
"docid": "MED-2374",
"text": "OBJECTIVES: To assess the dose-response relationship between egg consumption and the risk of cardiovascular diseases (CVD) and diabetes. METHODS: We systematically searched MEDLINE database through December 2012. Fixed- or random-effects model was used to pool the relative risks (RRs) and their 95% confidence intervals (CIs). Subgroup analyses was performed to explore the potential sources of heterogeneity. Weighted linear regression model was used to estimate the dose-response relationship. RESULTS: Fourteen studies involving 320,778 subjects were included. The pooled RRs of the risk of CVD, CVD for separated diabetes patients, and diabetes for the highest vs lowest egg intake were 1.19 (95% CI 1.02-1.38), 1.83 (95% CI 1.42-2.37), 1.68 (95% CI 1.41-2.00), respectively. For each 4/week increment in egg intake, the RRs of the risk for CVD, CVD for separated diabetes patients, diabetes was 1.06 (95% CI 1.03-1.10), 1.40 (95% CI 1.25-1.57), 1.29 (95% CI 1.21-1.37), respectively. Subgroup analyses showed that population in other western countries have increased CVD than ones in USA (RR 2.00, 95% CI 1.14 to 3.51 vs 1.13, 95% CI 0.98 to 1.30, P = 0.02 for subgroup difference). CONCLUSIONS: Our study suggests that there is a dose-response positive association between egg consumption and the risk of CVD and diabetes. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.",
"title": "Egg consumption and risk of cardiovascular diseases and diabetes: a meta-analysis."
},
{
"docid": "MED-2110",
"text": "Almost all types of newborn respiratory failure are reversible. However, supportive treatment (oxygen and positive airway pressure) can damage the lung, and newborn respiratory failure remains a major cause of morbidity and death in infants. Prolonged extracorporeal membrane oxygenation (ECMO) provides life support while allowing the lung to \"rest.\" We have used ECMO in 45 moribund newborn infants; 25 survived. Neonatologists referred patients who were unresponsive to maximal therapy. The right atrium and aortic arch were cannulated via the jugular vein and carotid artery. Heparin was infused continuously to main activated clotting time at 200 to 300 seconds. Airway oxygenation and pressure were reduced to low levels. Primary diagnoses were hyaline membrane disease, 14 (6 survived, 8 died); meconium aspiration, 22 (15 survived, 7 died); persistent fetal circulation including diaphragmatic hernia, 5 (3 survived, 2 died); and sepsis, 4 (1 survived, 3 died). Growth, development, and brain and lung function are normal in 20 of 25 survivors. ECMO decreased newborn respiratory failure mortality and morbidity rates in this phase I trial. A controlled randomized study is underway. The results suggest that ECMO may be effective in older patients if used before irreversible lung damage occurs.",
"title": "Extracorporeal membrane oxygenation for newborn respiratory failure: forty-five cases."
},
{
"docid": "MED-1403",
"text": "Background Several epidemiological studies have observed an increased risk of type 2 diabetes mellitus (T2DM) among subjects with a higher consumption of red and processed meat. Heme iron intake has been directly associated with a higher risk of T2DM in healthy adult Chinese and U.S populations. The objective of the present study was to evaluate the association between heme iron intake and the incidence of T2DM in a Mediterranean population at high cardiovascular risk. Methods We assessed a subset of participants in the PREDIMED trial as an observational cohort, followed up for a maximum of eight years. We initially included 1073 non-diabetic subjects (57.1% women) aged 67.3 ± 6.0 years, at high cardiovascular risk. Diet was assessed at the study baseline using a validated, semi-quantitative food frequency questionnaire. Results During the follow-up period 131 diabetics were newly diagnosed. The risk of developing T2DM was assessed using baseline heme iron intake and proportional hazard models, first unadjusted, then adjusted for energy, and finally adjusted for dietary, anthropometric, socio-demographic and lifestyle variables. Significant direct associations with the incidence of T2DM were found for heme iron (Hazard Ratio [HR] 1.30, 95% confidence interval [CI], 1.02 to 1.66). Secondarily, we have also observed that coffee (HR:0.93, 95% CI, 0.89 to 0.98) and alcoholic beverages (HR: 1.02, 95% CI, 1.01 to 1.04) were also found to reduce and increase the risk of T2DM, respectively. Conclusion High dietary intake of heme iron was associated with an increased risk of developing T2DM in a Mediterranean population at high cardiovascular risk. Trial registration Identifier: ISRCTN35739639.",
"title": "Heme iron intake and risk of new-onset diabetes in a Mediterranean population at high risk of cardiovascular disease: an observational cohort analysis"
},
{
"docid": "MED-1952",
"text": "There is growing interest in the long-term mental health sequelae of extremely preterm birth. In this paper we review literature relating to mental health outcomes across the lifespan. Studies conducted in the preschool years, school age and adolescence, and adulthood show continuity in outcomes and point to an increased risk for inattention, socio-communicative problems and emotional difficulties in individuals born extremely preterm. Both behavioural and neuroimaging studies also provide evidence of a neurodevelopmental origin for mental health disorders in this population. Here we summarise contemporary evidence and highlight key methodological considerations for carrying out and interpreting studies in this field. Copyright © 2013 Elsevier Ltd. All rights reserved.",
"title": "Growing up after extremely preterm birth: lifespan mental health outcomes."
},
{
"docid": "MED-1530",
"text": "BACKGROUND: Prospective cohort studies have examined mortality and overall cancer incidence among vegetarians, but the results have been inconclusive. AIMS: The objective of the present meta-analysis was to investigate cardiovascular disease mortality and cancer incidence among vegetarians and nonvegetarians. METHODS: Medline, EMBASE and Web Of Science databases were searched for cohort studies published from inception to September 2011. Studies were included if they contained the relative risk (RR) and corresponding 95% CI. Participants were from the UK, Germany, California, USA, the Netherlands and Japan. RESULTS: Seven studies with a total of 124,706 participants were included in this analysis. All-cause mortality in vegetarians was 9% lower than in nonvegetarians (RR = 0.91; 95% CI, 0.66-1.16). The mortality from ischemic heart disease was significantly lower in vegetarians than in nonvegetarians (RR = 0.71; 95% CI, 0.56-0.87). We observed a 16% lower mortality from circulatory diseases (RR = 0.84; 95% CI, 0.54-1.14) and a 12% lower mortality from cerebrovascular disease (RR = 0.88; 95% CI, 0.70-1.06) in vegetarians compared with nonvegetarians. Vegetarians had a significantly lower cancer incidence than nonvegetarians (RR = 0.82; 95% CI, 0.67-0.97). CONCLUSIONS: Our results suggest that vegetarians have a significantly lower ischemic heart disease mortality (29%) and overall cancer incidence (18%) than nonvegetarians. Copyright © 2012 S. Karger AG, Basel.",
"title": "Cardiovascular disease mortality and cancer incidence in vegetarians: a meta-analysis and systematic review."
},
{
"docid": "MED-4239",
"text": "BACKGROUND: Prostate cancer is the most common solid-tumor cancer in US males but is rare in Asian males. When Asian men adopt the US lifestyle, clinical prostate cancer increases greatly. Epidemiological data from men in the US indicate that regular activity may reduce the risk for prostate cancer. METHODS: Serum was obtained from three groups of similar-aged men, Control, Diet and Exercise, and Exercise alone were used to stimulate LNCaP cells in culture. Growth and apoptosis of tumor cells were measured. Serum samples were also used to measure insulin, IGF-1, IGFBP-1. RESULTS: The Diet and Exercise and the Exercise alone groups had lower serum insulin and IGF-1 but higher IGFBP-1 compared to Controls. LNCaP cell growth was reduced in both groups compared to Control and there was a major increase in apoptosis of tumor cells. CONCLUSIONS: A low-fat diet and/or intensive exercise results in change in serum hormones and growth factors in vivo that can reduce growth and induce apoptosis of LNCaP prostate tumor cells in vitro. Copyright 2003 Wiley-Liss, Inc.",
"title": "A low-fat diet and/or strenuous exercise alters the IGF axis in vivo and reduces prostate tumor cell growth in vitro."
},
{
"docid": "MED-1872",
"text": "CONTEXT: Weight loss, sodium reduction, increased physical activity, and limited alcohol intake are established recommendations that reduce blood pressure (BP). The Dietary Approaches to Stop Hypertension (DASH) diet also lowers BP. To date, no trial has evaluated the effects of simultaneously implementing these lifestyle recommendations. OBJECTIVE: To determine the effect on BP of 2 multicomponent, behavioral interventions. DESIGN, SETTING, AND PARTICIPANTS: Randomized trial with enrollment at 4 clinical centers (January 2000-June 2001) among 810 adults (mean [SD] age, 50 [8.9] years; 62% women; 34% African American) with above-optimal BP, including stage 1 hypertension (120-159 mm Hg systolic and 80-95 mm Hg diastolic), and who were not taking antihypertensive medications. INTERVENTION: Participants were randomized to one of 3 intervention groups: (1) \"established,\" a behavioral intervention that implemented established recommendations (n = 268); (2) \"established plus DASH,\"which also implemented the DASH diet (n = 269); and (3) an \"advice only\" comparison group (n = 273). MAIN OUTCOME MEASURES: Blood pressure measurement and hypertension status at 6 months. RESULTS: Both behavioral interventions significantly reduced weight, improved fitness, and lowered sodium intake. The established plus DASH intervention also increased fruit, vegetable, and dairy intake. Across the groups, gradients in BP and hypertensive status were evident. After subtracting change in advice only, the mean net reduction in systolic BP was 3.7 mm Hg (P<.001) in the established group and 4.3 mm Hg (P<.001) in the established plus DASH group; the systolic BP difference between the established and established plus DASH groups was 0.6 mm Hg (P =.43). Compared with the baseline hypertension prevalence of 38%, the prevalence at 6 months was 26% in the advice only group, 17% in the established group (P =.01 compared with the advice only group), and 12% in the established plus DASH group (P<.001 compared with the advice only group; P =.12 compared with the established group). The prevalence of optimal BP (<120 mm Hg systolic and <80 mm Hg diastolic) was 19% in the advice only group, 30% in the established group (P =.005 compared with the advice only group), and 35% in the established plus DASH group (P<.001 compared with the advice only group; P =.24 compared with the established group). CONCLUSION: Individuals with above-optimal BP, including stage 1 hypertension, can make multiple lifestyle changes that lower BP and reduce their cardiovascular disease risk.",
"title": "Effects of comprehensive lifestyle modification on blood pressure control: main results of the PREMIER clinical trial."
},
{
"docid": "MED-1817",
"text": "Pancreatic cancer is the fourth most common cause of cancer death worldwide with large geographical variation, which implies the contribution of diet and lifestyle in its etiology. We examined the association of meat and fish consumption with risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC). A total of 477,202 EPIC participants from 10 European countries recruited between 1992 and 2000 were included in our analysis. Until 2008, 865 nonendocrine pancreatic cancer cases have been observed. Calibrated relative risks (RRs) and 95% confidence intervals (CIs) were computed using multivariable-adjusted Cox hazard regression models. The consumption of red meat (RR per 50 g increase per day = 1.03, 95% CI = 0.93-1.14) and processed meat (RR per 50 g increase per day = 0.93, 95% CI = 0.71-1.23) were not associated with an increased pancreatic cancer risk. Poultry consumption tended to be associated with an increased pancreatic cancer risk (RR per 50 g increase per day = 1.72, 95% CI = 1.04-2.84); however, there was no association with fish consumption (RR per 50 g increase per day = 1.22, 95% CI = 0.92-1.62). Our results do not support the conclusion of the World Cancer Research Fund that red or processed meat consumption may possibly increase the risk of pancreatic cancer. The positive association of poultry consumption with pancreatic cancer might be a chance finding as it contradicts most previous findings. Copyright © 2012 UICC.",
"title": "Meat and fish consumption and risk of pancreatic cancer: results from the European Prospective Investigation into Cancer and Nutrition."
},
{
"docid": "MED-4237",
"text": "OBJECTIVE: To evaluate the prevalence of benign prostatic hyperplasia (BPH) and prostatic cancer (CaP) in the mainland of China. METHODS: The incidence of BPH and CaP in urological hospital was investigated in 1997 in 26 provinces and 4 metropolises scattered over the mainland of China. The change of hospital incidences of BPH and CaP in the Institute of Urology, Beijing Medical University from 1951 to 1997 was also reviewed. RESULTS: The incidence of BPH and CaP in 1997 in 187 hospitals scattered over the mainland of China was 16.1% (15,459/95,749) and 1.5% (1389/95,749), respectively. The incidence of BPH and CaP in the Institute of Urology, Beijing University from 1951 to 1960 was 7.6% and 0.6%, respectively, while it was 18.5% and 3.4% from 1991 to 1997. CONCLUSION: The hospital incidence of BPH and CaP is rising rapidly in China, but CaP is still not a common disease in China.",
"title": "Epidemiological survey of benign prostatic hyperplasia and prostatic cancer in China."
},
{
"docid": "MED-1665",
"text": "Insufficient blood supply to the intervertebral disc (IVD) has been proposed to play a role as causative factor in IVD degeneration. There is an association between IVD diseases and increased risk of dying of ischaemic heart disease. Obesity and tobacco are potential risk factors for degenerative IVD disease. High blood cholesterol and triglycerides serum levels are risk factors for atherosclerosis, and could be responsible for a decreased in the blood supply to the already poor vascularized IVD. We performed a frequency-matched case–control study to determine the serum levels of patients with symptomatic herniated lumbar disc. We examined the fasting serum lipid levels in 384 subjects who were operated at our institution. Group 1 included 169 consecutive patients (115 men and 54 women; mean age: 59.1 years, range 29–85) who underwent surgery for symptomatic disc herniation. Group 2 (control group) included 169 patients (115 men and 54 women; mean age: 61 years, range 26–86) who underwent arthroscopic meniscectomy for a meniscal tear in the same period. These patients were frequency-matched by age (within 3 years) and gender with patients of Group 1. Sera were extracted from blood samples and the concentrations of total cholesterol (TC) and triglycerides (TG) were determined. When comparing the two groups, patients with symptomatic herniated lumbar disc showed statistically significant higher triglyceride concentration (P = 0.02) and total cholesterol concentration (P = 0.01). Serum lipid levels may be a risk factor for IVD pathology. An enhanced understanding of these factors holds the promise of new approaches to the prevention and management of IVD pathology.",
"title": "Symptomatic disc herniation and serum lipid levels"
},
{
"docid": "MED-2091",
"text": "BACKGROUND: The aim of this study was to evaluate and compare the effectiveness of 0.5% tea, 2% neem, and 0.2% chlorhexidine mouthwashes on oral health. MATERIALS AND METHODS: A randomized blinded controlled trial with 30 healthy human volunteers of age group 18-25 years was carried out. The subjects were randomly assigned to 3 groups i.e., group A - 0.2% chlorhexidine gluconate (bench mark control), Group B - 2% neem, and group C - 0.5% tea of 10 subjects per group. Plaque accumulation and gingival condition were recorded using plaque index and gingival index. Oral hygiene was assessed by simplified oral hygiene index (OHIS). Salivary pH was assessed by indikrom pH strips. Plaque, gingival, and simplified OHI scores as well as salivary pH were recorded at baseline, immediately after 1 st rinse, after 1 week, 2 nd week, and 3 rd week. The 3 rd week was skipped for group A. RESULTS: Mean plaque and gingival scores were reduced over the 3 week trial period for experimental and control groups. Anti-plaque effectiveness was observed in all groups and the highest being in group C (P < 0.05). Neem and tea showed comparative effectiveness on gingiva better than chlorhexidine (P < 0.05). The salivary pH rise was sustained and significant in Group B and C compared to Group A. Oral hygiene improvement was better appreciated in Group B and Group C. CONCLUSION: The effectiveness of 0.5% tea was more compared to 2% neem and 0.2% chlorhexidine mouth rinse.",
"title": "Comparison of the effectiveness of 0.5% tea, 2% neem and 0.2% chlorhexidine mouthwashes on oral health: a randomized control trial."
},
{
"docid": "MED-3800",
"text": "OBJECTIVE: To review the current management of women with breast pain. OPTIONS: The effect of various treatment modes and health practices, including medications, was considered for the management of both cyclical and noncyclical breast pain. OUTCOMES: Effective and timely management of the woman with breast pain and improved quality of life. EVIDENCE: A literature search was performed to identify reports published in English between 1975 and July 2003 using MEDLINE and Cochrane Database of Systematic Reviews. VALUES: Levels of evidence, as outlined, have been determined using the criteria outlined by the Canadian Task Force on the Periodic Health Examination. Participants were the principal authors: a clinical dietitian, a surgeon oncologist, and a nurse. BENEFITS, HARMS, AND COSTS: Utilizing the information will increase knowledge, enabling a consistent approach, which will reduce the number of ineffective interventions and ensure appropriate use medications. VALIDATION: Comparison has been made with management protocols in the literature, but no clinical guidelines have been located. No formal clinical testing has taken place. SPONSOR: The Society of Obstetricians and Gynaecologists of Canada (SOGC). Work on these guidelines was initiated by team members to fill a need for practice guidelines at Winnipeg Regional Health Authority Breast Health Centre, Winnipeg, MB. RECOMMENDATIONS: 1. Education and reassurance is an integral part of the management of mastalgia and should be the first-line treatment. (II-1 A) 2. The use of a well-fitting bra that provides good support should be considered for the relief of cyclical and noncyclical mastalgia. (II-3 B) 3. A change in dose, formulation, or scheduling should be considered for women on HRT. HRT may be discontinued if appropriate. (III C) 4. Women with breast pain should not be advised to reduce caffeine intake. (1 E) 5. Vitamin E should not be considered for the treatment of mastalgia. (1 E) 6. There is presently insufficient evidence to recommend the use of evening primrose oil (EPO) in the treatment of breast pain. (II-2 C) 7. Flaxseed should be considered as a first-line treatment for cyclical mastalgia. (I A) 8. Topical non-steroidal anti-inflammatory gel, such as diclofenac 2% in pluronic lethicin organogel, should be considered for pain control for localized treatment of mastalgia. (I A) 9. Tamoxifen 10 mg daily or danazol 200 mg daily should be considered when first-line treatments are ineffective. (I A) 10. Mastectomy or partial mastectomy should not be considered an effective treatment for mastalgia. (III E).",
"title": "Mastalgia."
},
{
"docid": "MED-2292",
"text": "In industrialized nations, diverticular disease affects up to 70% of individuals by 60 years of age, with symptoms that can range from mild gastrointestinal disturbance to incapacitating pain. Diverticular disease appears to be related to increasing affluence and changed diet: Current theory holds that diverticular disease's origin is low-fiber diet. This explains why its incidence is highest and accelerating in the more prosperous countries where intake of fiber has decreased and intake of milled grains and refined sugars has increased over time. Not all patients develop symptoms, but if they do, the most frequent complaints associated with diverticulosis are cramping in the left-lower quadrant, bloating, constipation, and soiling. If diverticula perforate the gut's wall into the pericolic tissue, small and large abscesses, accompanied by bleeding, can form. Fistulization, when it occurs, most often penetrates to the bladder. Treatment addresses symptoms and may require hospitalization. During symptomatic periods, patients do best on low-fiber, bland diets. Once the acute episode or highly symptomatic period resolves or chronic disease is managed, patients should gradually increase dietary fiber to 20 to 30 grams daily or take dietary fiber in the form of bulk stimulants like psyllium.",
"title": "Diverticular disease: eat your fiber!"
},
{
"docid": "MED-1866",
"text": "Polyphenols from Hibiscus sabdariffa calices were administered to patients with metabolic syndrome (125 mg/kg/day for 4 wk, n = 31) and spontaneously hypertensive rats (125 or 60 mg/kg in a single dose or daily for 1 wk, n = 8 for each experimental group). The H. sabdariffa extract improved metabolism, displayed potent anti-inflammatory and antioxidant activities, and significantly reduced blood pressure in both humans and rats. Diuresis and inhibition of the angiotensin I-converting enzyme were found to be less important mechanisms than those related to the antioxidant, anti-inflammatory, and endothelium-dependent effects to explain the beneficial actions. Notably, polyphenols induced a favorable endothelial response that should be considered in the management of metabolic cardiovascular risks. © 2014 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.",
"title": "Hibiscus sabdariffa extract lowers blood pressure and improves endothelial function."
},
{
"docid": "MED-3799",
"text": "Modifiable factors, including diet, might alter breast cancer risk. We used the WHI Dietary Modification (DM) trial to test the effect of the intervention on risk of benign proliferative breast disease, a condition associated with increased risk of and considered to be on the pathway to invasive breast cancer. The WHI DM trial was a randomized, controlled, primary prevention trial conducted in 40 US clinical centers from 1993–2005. 48,835 postmenopausal women, aged 50–79 years, without prior breast cancer, were enrolled. Participants were randomly assigned to the DM intervention group or to the comparison group. The intervention was designed to reduce total dietary fat intake to 20% of total energy intake, and to increase fruit and vegetable intake to ≥5 servings/day and intake of grain products to ≥6 servings/day, but resulted in smaller, albeit significant changes in practice. Participants had biennial mammograms and regular clinical breast exams. We identified women who reported breast biopsies free of cancer, obtained the histologic sections, and subjected them to standardized central review. During follow-up (average, 7.7 years), 570 incident cases of benign proliferative breast disease were ascertained in the intervention group and 793 in the comparison group. The hazard ratio for the association between DM and benign proliferative breast disease was 1.09 (95%CI, 0.98–1.23). Risk varied by levels of baseline total vitamin D intake but it varied little by levels of other baseline variables. These results suggest that a modest reduction in fat intake and increase in fruit, vegetable, and grain intake does not alter the risk of benign proliferative breast disease.",
"title": "Low-fat dietary pattern and risk of benign proliferative breast disease: a randomized, controlled dietary modification trial"
},
{
"docid": "MED-1406",
"text": "The relation between dietary magnesium intake and cardiovascular disease (CVD) or mortality was evaluated in several prospective studies, but few of them have assessed the risk of all-cause mortality, which has never been evaluated in Mediterranean adults at high cardiovascular risk. The aim of this study was to assess the association between magnesium intake and CVD and mortality risk in a Mediterranean population at high cardiovascular risk with high average magnesium intake. The present study included 7216 men and women aged 55-80 y from the PREDIMED (Prevención con Dieta Mediterránea) study, a randomized clinical trial. Participants were assigned to 1 of 2 Mediterranean diets (supplemented with nuts or olive oil) or to a control diet (advice on a low-fat diet). Mortality was ascertained by linkage to the National Death Index and medical records. We fitted multivariable-adjusted Cox regressions to assess associations between baseline energy-adjusted tertiles of magnesium intake and relative risk of CVD and mortality. Multivariable analyses with generalized estimating equation models were used to assess the associations between yearly repeated measurements of magnesium intake and mortality. After a median follow-up of 4.8 y, 323 total deaths, 81 cardiovascular deaths, 130 cancer deaths, and 277 cardiovascular events occurred. Energy-adjusted baseline magnesium intake was inversely associated with cardiovascular, cancer, and all-cause mortality. Compared with lower consumers, individuals in the highest tertile of magnesium intake had a 34% reduction in mortality risk (HR: 0.66; 95% CI: 0.45, 0.95; P < 0.01). Dietary magnesium intake was inversely associated with mortality risk in Mediterranean individuals at high risk of CVD. This trial was registered at controlled-trials.com as ISRCTN35739639.",
"title": "Dietary magnesium intake is inversely associated with mortality in adults at high cardiovascular disease risk."
},
{
"docid": "MED-2136",
"text": "Prostate cancer (PCa) is dependent on androgen receptor signaling and aberrations of the PI3K-Akt-mTORC1 pathway mediating excessive and sustained growth signaling. The nutrient-sensitive kinase mTORC1 is upregulated in nearly 100% of advanced human PCas. Oncogenic mTORC1 signaling activates key subsets of mRNAs that cooperate in distinct steps of PCa initiation and progression. Epidemiological evidence points to increased dairy protein consumption as a major dietary risk factor for the development of PCa. mTORC1 is a master regulator of protein synthesis, lipid synthesis and autophagy pathways that couple nutrient sensing to cell growth and cancer. This review provides evidence that PCa initiation and progression are promoted by cow´s milk, but not human milk, stimulation of mTORC1 signaling. Mammalian milk is presented as an endocrine signaling system, which activates mTORC1, promotes cell growth and proliferation and suppresses autophagy. Naturally, milk-mediated mTORC1 signaling is restricted only to the postnatal growth phase of mammals. However, persistent consumption of cow´s milk proteins in humans provide highly insulinotropic branched-chain amino acids (BCAAs) provided by milk´s fast hydrolysable whey proteins, which elevate postprandial plasma insulin levels, and increase hepatic IGF-1 plasma concentrations by casein-derived amino acids. BCAAs, insulin and IGF-1 are pivotal activating signals of mTORC1. Increased cow´s milk protein-mediated mTORC1 signaling along with constant exposure to commercial cow´s milk estrogens derived from pregnant cows may explain the observed association between high dairy consumption and increased risk of PCa in Westernized societies. As well-balanced mTORC1-signaling plays an important role in appropriate prostate morphogenesis and differentiation, exaggerated mTORC1-signaling by high cow´s milk consumption predominantly during critical growth phases of prostate development and differentiation may exert long-term adverse effects on prostate health. Attenuation of mTORC1 signaling by contemporary Paleolithic diets and restriction of dairy protein intake, especially during mTORC1-dependent phases of prostate development and differentiation, may offer protection from the most common dairy-promoted cancer in men of Western societies.",
"title": "The impact of cow's milk-mediated mTORC1-signaling in the initiation and progression of prostate cancer"
},
{
"docid": "MED-3443",
"text": "Incidence of the metabolic syndrome is increasing worldwide, with notable exceptions of some Asian countries where seaweeds are commonly consumed. 13 men (mean age 47.4+/-9.9 yr) and 14 women (average age 45.6+/-12.2 yr) with at least one symptom of the metabolic syndrome were recruited in Quito Ecuador to a randomized double-blinded placebo-controlled trial. Subjects were assigned to either Group 1 (1 m placebo, followed by 1 m 4 g/d seaweed [Undaria pinnatifida]) or Group 2 (1 m of 4 g/d seaweed, followed by 1 m of 6 g/d of seaweed). Blood pressure, weight, waist circumference, inflammation biomarkers, and lipids were measured monthly. Repeated measures analysis of variance with Tukey's multiple comparison tests were used for statistical analysis. In Group 2, systolic blood pressure decreased 10.5 mmHg after a month of 6 g/d seaweed (95% CI: 4.1, 16.8 mmHg; p<0.05), primarily in subjects with high-normal baseline blood pressure. Waist circumference changed only for women participants, with a 2.4 cm decrease in Group 1 after treatment with placebo (95% CI: 1.0, 3.7 cm; p<0.01). In Group 2, women had a mean decrease of 2.1 cm after 4 g/d (95% CI: 0.4, 3.7 cm; p<0.05) and a further 1.8 cm decrease after 1 m 6 g/d seaweed (95 % CI: 0.1, 3.4, p<0.05). No other changes were observed. Consumption of 4 to 6 g/d seaweed, typical for most people in Japan, may be associated with low metabolic syndrome prevalence.",
"title": "Could dietary seaweed reverse the metabolic syndrome?"
},
{
"docid": "MED-2572",
"text": "In traditional cultures, balancing health with a balanced lifestyle was a core belief. The diseases of modern civilization were rare. Indigenous people have patterns of illness very different from Western civilization; yet, they rapidly develop diseases once exposed to Western foods and lifestyles. Food and medicine were interwoven. All cultures used special or functional foods to prevent disease. Food could be used at different times either as food or medicine. Foods, cultivation, and cooking methods maximized community health and well-being. With methods passed down through generations, cooking processes were utilized that enhanced mineral and nutrient bioavailability. This article focuses on what researchers observed about the food traditions of indigenous people, their disease patterns, the use of specific foods, and the environmental factors that affect people who still eat traditional foods.",
"title": "Traditional non-Western diets."
},
{
"docid": "MED-1505",
"text": "The important role of diet in cardiometabolic health is generally well recognised; for mental health, it is not so well understood. However, lifestyle risk factors for poor physical health are the same risk factors for mental illness, including poor diet. This is reflected by the high level of poor physical health in people with mental illness. Mediterranean, whole food diets have been associated with reduced risk for chronic disease, but very little research has investigated their mental health benefits. We provide a model for the pathways by which food components provided by a Mediterranean-style diet can facilitate healthy brain function. We then review evidence for the role of selected nutrients/food components - antioxidants, omega-3 fatty acids and B vitamins - in the brain and, hence, modulation of cognitive function and mental health. Converging evidence indicates multiple pathways by which these nutrients can assist in brain function, drawing from studies investigating them in isolation. There is very little work done on synergistic actions of nutrients and whole diets, highlighting a need for human intervention studies investigating benefits of Mediterranean-style diets for mental, as well as cardiometabolic health. Copyright © 2013 Elsevier Inc. All rights reserved.",
"title": "Nutritional modulation of cognitive function and mental health."
},
{
"docid": "MED-1820",
"text": "Background This study aims to comprehensively summarize the currently available evidences on the efficacy and safety of gemcitabine plus erlotinib for treating advanced pancreatic cancer. Methodology/Principal Findings PubMed, EMBASE, The Cochrane Library and abstracts of recent major conferences were systematically searched to identify relevant publications. Studies that were conducted in advanced pancreatic cancer patients treated with gemcitabine plus erlotinib (with or without comparison with gemcitabine alone) and reporting objective response rate, disease control rate, progression-free survival, time-to-progression, overall survival, 1-year survival rate and/or adverse events were included. Data on objective response rate, disease control rate, 1-year survival rate and adverse events rate, respectively, were combined mainly by using Meta-Analyst software with a random-effects model. Data on progression-free survival, time-to-progression and overall survival were summarized descriptively. Sixteen studies containing 1,308 advanced pancreatic cancer patients treated with gemcitabine plus erlotinib were included. The reported median progression-free survival (or time-to-progression), median overall survival, 1-year survival rates, objective response rates and disease control rates were 2–9.6 months, 5–12.5 months, 20%–51%, 0%–28.6% and 25.0%–83.3%, respectively. The weighted 1-year survival rate, objective response rate and disease control rate based on studies reporting robust results were 27.9%, 9.1% and 57.0%, respectively. According to the studies with relevant data, the incidences of total and severe adverse events were 96.3% and 62.9%, respectively. The most frequently reported adverse events were leucopenia, rash, diarrhea, vomitting, neutropenia, thrombocytopenia, anaemia, stomatitis, drug-induced liver injury, fatigue and fever. Compared with gemcitabine alone, the progression-free survival and overall survival with gemcitabine plus erlotinib were significantly longer, but there were also more deaths and interstitial lung disease-like syndrome related to this treatment. Conclusions/Significance Gemcitabine plus erlotinib represent a new option for the treatment of advanced pancreatic cancer, with mild but clinically meaningful additive efficacy compared with gemcitabine alone. Its safety profile is generally acceptable, although careful management is needed for some specific adverse events.",
"title": "Gemcitabine Plus Erlotinib for Advanced Pancreatic Cancer: A Systematic Review with Meta-Analysis"
},
{
"docid": "MED-2946",
"text": "OBJECTIVE: Vegetarians are more vascular-healthy but those with subnormal vitamin B-12 status have impaired arterial endothelial function and increased intima-media thickness. We aimed to study the impact of vitamin B-12 supplementation on these markers, in the vegetarians. DESIGN: Double-blind, placebo controlled, randomised crossover study. SETTING: Community dwelling vegetarians. PARTICIPANTS: Fifty healthy vegetarians (vegetarian diet for at least 6 years) were recruited. INTERVENTION: Vitamin B-12 (500 µg/day) or identical placebo were given for 12 weeks with 10 weeks of placebo-washout before crossover (n=43), and then open label vitamin B-12 for additional 24 weeks (n=41). MEASUREMENT: Flow-mediated dilation of brachial artery (FMD) and intima-media thickness (IMT) of carotid artery were measured by ultrasound. RESULTS: The mean age of the subjects was 45±9 years and 22 (44%) were male. Thirty-five subjects (70%) had serum B-12 levels <150 pmol/l. Vitamin B-12 supplementation significantly increased serum vitamin B-12 levels (p<0.0001) and lowered plasma homocysteine (p<0.05). After vitamin B-12 supplementation but not placebo, significant improvement of brachial FMD (6.3±1.8% to 6.9±1.9%; p<0.0001) and in carotid IMT (0.69±0.09 mm to 0.67±0.09 mm, p<0.05) were found, with further improvement in FMD (to 7.4±1.7%; p<0.0001) and IMT (to 0.65±0.09 mm; p<0.001) after 24 weeks open label vitamin B-12. There were no significant changes in blood pressures or lipid profiles. On multivariate analysis, changes in B-12 (β=0.25; p=0.02) but not homocysteine were related to changes in FMD, (R=0.32; F value=3.19; p=0.028). CONCLUSIONS: Vitamin B-12 supplementation improved arterial function in vegetarians with subnormal vitamin B-12 levels, proposing a novel strategy for atherosclerosis prevention.",
"title": "Vitamin B-12 supplementation improves arterial function in vegetarians with subnormal vitamin B-12 status."
},
{
"docid": "MED-1192",
"text": "Objectives To determine the quantitative efficacy of different classes of blood pressure lowering drugs in preventing coronary heart disease (CHD) and stroke, and who should receive treatment. Design Meta-analysis. Data source Medline (1966-2007). Study selection Randomised trials of blood pressure lowering drugs recording CHD events and strokes. 108 trials studied differences in blood pressure between study drug and placebo (or control group not receiving the study drug) (“blood pressure difference trials”), and 46 trials compared drugs (“drug comparison trials”). Seven trials with three randomised groups fell into both categories. The results were interpreted in the context of those expected from the largest published meta-analysis of cohort studies, totalling 958 000 people. Participants 464 000 people defined into three mutually exclusive categories: participants with no history of vascular disease, a history of CHD, or a history of stroke. Results In the blood pressure difference trials β blockers had a special effect over and above that due to blood pressure reduction in preventing recurrent CHD events in people with a history of CHD: risk reduction 29% (95% confidence interval 22% to 34%) compared with 15% (11% to 19%) in trials of other drugs. The extra effect was limited to a few years after myocardial infarction, with a risk reduction of 31% compared with 13% in people with CHD with no recent infarct (P=0.04). In the other blood pressure difference trials (excluding CHD events in trials of β blockers in people with CHD), there was a 22% reduction in CHD events (17% to 27%) and a 41% (33% to 48%) reduction in stroke for a blood pressure reduction of 10 mm Hg systolic or 5 mm Hg diastolic, similar to the reductions of 25% (CHD) and 36% (stroke) expected for the same difference in blood pressure from the cohort study meta-analysis, indicating that the benefit is explained by blood pressure reduction itself. The five main classes of blood pressure lowering drugs (thiazides, β blockers, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and calcium channel blockers) were similarly effective (within a few percentage points) in preventing CHD events and strokes, with the exception that calcium channel blockers had a greater preventive effect on stroke (relative risk 0.92, 95% confidence interval 0.85 to 0.98). The percentage reductions in CHD events and stroke were similar in people with and without cardiovascular disease and regardless of blood pressure before treatment (down to 110 mm Hg systolic and 70 mm Hg diastolic). Combining our results with those from two other studies (the meta-analyses of blood pressure cohort studies and of trials determining the blood pressure lowering effects of drugs according to dose) showed that in people aged 60-69 with a diastolic blood pressure before treatment of 90 mm Hg, three drugs at half standard dose in combination reduced the risk of CHD by an estimated 46% and of stroke by 62%; one drug at standard dose had about half this effect. The present meta-analysis also showed that drugs other than calcium channel blockers (with the exception of non-cardioselective β blockers) reduced the incidence of heart failure by 24% (19% to 28%) and calcium channel blockers by 19% (6% to 31%). Conclusions With the exception of the extra protective effect of β blockers given shortly after a myocardial infarction and the minor additional effect of calcium channel blockers in preventing stroke, all the classes of blood pressure lowering drugs have a similar effect in reducing CHD events and stroke for a given reduction in blood pressure so excluding material pleiotropic effects. The proportional reduction in cardiovascular disease events was the same or similar regardless of pretreatment blood pressure and the presence or absence of existing cardiovascular disease. Guidelines on the use of blood pressure lowering drugs can be simplified so that drugs are offered to people with all levels of blood pressure. Our results indicate the importance of lowering blood pressure in everyone over a certain age, rather than measuring it in everyone and treating it in some.",
"title": "Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies"
},
{
"docid": "MED-3103",
"text": "The mucosal immune system is constantly exposed to a wide range of commensal and potentially pathogenic microbial species. Chronic exposure to foreign organisms makes generation of an appropriate immune response critical in maintaining a balance between elimination of harmful pathogens, peaceful coexistence with commensals, and prevention of autoimmunity. Intestinal intraepithelial lymphocytes provide a first line of defense at this extensive barrier with the outside world, and as such, understanding their role in immunity is critical.",
"title": "Intraepithelial Lymphocytes: To Serve and Protect"
},
{
"docid": "MED-1666",
"text": "STUDY DESIGN: A review of the literature on disc nutrition. OBJECTIVES: To summarize the information on disc nutrition in relation to disc degeneration. SUMMARY OF THE BACKGROUND DATA: The disc is avascular, and the disc cells depend on diffusion from blood vessels at the disc's margins to supply the nutrients essential for cellular activity and viability and to remove metabolic wastes such as lactic acid. The nutrient supply can fail due to changes in blood supply, sclerosis of the subchondral bone or endplate calcification, all of which can block transport from blood supply to the disc or due to changes in cellular demand. METHODS: A review of the studies on disc blood supply, solute transport, studies of solute transport in animal and human disc in vitro, and of theoretical modeling studies that have examined factors affecting disc nutrition. RESULTS: Small nutrients such as oxygen and glucose are supplied to the disc's cells virtually entirely by diffusion; convective transport, arising from load-induced fluid movement in and out of the disc, has virtually no direct influence on transport of these nutrients. Consequently, there are steep concentration gradients of oxygen, glucose, and lactic acid across the disc; oxygen and glucose concentrations are lowest in the center of the nucleus where lactic acid concentrations are greatest. The actual levels of concentration depend on the balance between diffusive transport and cellular demand and can fall to critical levels if the endplate calcifies or nutritional demand increases. CONCLUSIONS: Loss of nutrient supply can lead to cell death, loss of matrix production, and increase in matrix degradation and hence to disc degeneration.",
"title": "Nutrition of the intervertebral disc."
},
{
"docid": "MED-3280",
"text": "Conventional chemotherapies have showed their limits, notably for patients with advanced cancer. New therapeutic strategies must be identified, and the metabolic abnormalities of cancer cells offer such opportunities. Many human cancer cell lines and primary tumors have absolute requirements for methionine, an essential amino acid. In contrast, normal cells are relatively resistant to exogenous methionine restriction. The biochemical mechanism for methionine dependency has been studied extensively, but the fundamental mechanism remains unclear. A number of investigators have attempted to exploit the methionine dependence of tumors for therapeutic effects in vivo. To reduce in vivo methionine in plasma and tumours, dietary and pharmacological treatments have been used. Methionine-free diet or methionine-deprived total parenteral nutrition causes regression of a variety of animal tumours. Alternatively, methionine depletion was achieved by the use of methioninase. This enzyme specifically degrades methionine and inhibits tumour growth in preclinical models. Because of potential toxicity and quality of life problems, prolonged methionine restriction with diet or with methioninase is not suitable for clinical use. Methionine restriction may find greater application in association with various chemotherapeutic agents. Several preclinical studies have demonstrated synergy between methionine restriction and various cytotoxic chemotherapy drugs. The experimental results accumulated during the last three decades suggest that methionine restriction can become an additional cancer therapeutic strategy, notably in association with chemotherapy.",
"title": "Methionine dependency and cancer treatment."
},
{
"docid": "MED-4689",
"text": "Background A plant-based diet protects against chronic oxidative stress-related diseases. Dietary plants contain variable chemical families and amounts of antioxidants. It has been hypothesized that plant antioxidants may contribute to the beneficial health effects of dietary plants. Our objective was to develop a comprehensive food database consisting of the total antioxidant content of typical foods as well as other dietary items such as traditional medicine plants, herbs and spices and dietary supplements. This database is intended for use in a wide range of nutritional research, from in vitro and cell and animal studies, to clinical trials and nutritional epidemiological studies. Methods We procured samples from countries worldwide and assayed the samples for their total antioxidant content using a modified version of the FRAP assay. Results and sample information (such as country of origin, product and/or brand name) were registered for each individual food sample and constitute the Antioxidant Food Table. Results The results demonstrate that there are several thousand-fold differences in antioxidant content of foods. Spices, herbs and supplements include the most antioxidant rich products in our study, some exceptionally high. Berries, fruits, nuts, chocolate, vegetables and products thereof constitute common foods and beverages with high antioxidant values. Conclusions This database is to our best knowledge the most comprehensive Antioxidant Food Database published and it shows that plant-based foods introduce significantly more antioxidants into human diet than non-plant foods. Because of the large variations observed between otherwise comparable food samples the study emphasizes the importance of using a comprehensive database combined with a detailed system for food registration in clinical and epidemiological studies. The present antioxidant database is therefore an essential research tool to further elucidate the potential health effects of phytochemical antioxidants in diet.",
"title": "The total antioxidant content of more than 3100 foods, beverages, spices, herbs and supplements used worldwide"
},
{
"docid": "MED-2800",
"text": "The management of osteoarthritis represents a real challenge. This complex and multi-factorial disease evolves over decades and requires not only the alleviation of symptoms, i.e. pain and joint function but also the preservation of articular structure without side effects. Nutraceuticals are good candidates for the management of OA due to their safety profile and potential efficacy. However, they are not part of the treatment guidelines and published recommendations. Curcumin is the yellow pigment isolated from the rhizomes of Curcuma longa, commonly known as turmeric. Curcumin is a highly pleiotropic molecule with an excellent safety profile. Strong molecular evidence has been published for its potency to target multiple inflammatory diseases. However, naturally occurring curcumin cannot achieve its optimum therapeutic outcomes due to its low solubility and poor bioavailability. Nevertheless, curcumin presents great potential for treating OA and has been categorized as having preclinical evidence of efficacy. This review aimed at gathering most of the available information to document the potential efficacy of curcumin based on the results obtained in in vitro models of cartilage and osteoarthritis and in other diseases.",
"title": "Curcumin: a new paradigm and therapeutic opportunity for the treatment of osteoarthritis: curcumin for osteoarthritis management"
},
{
"docid": "MED-1663",
"text": "STUDY DESIGN: A cross-sectional analysis of the feeding arteries of the lumbar spine and cholesterol levels on patients with long-term nonspecific lower back pain. OBJECTIVES: To evaluate whether occlusion of lumbar and middle sacral arteries or serum cholesterol levels are associated with lower back pain and/or with disc degeneration. SUMMARY OF BACKGROUND DATA: Atherosclerosis in the wall of the abdominal aorta usually develops at the ostia of branching arteries and the bifurcation, and may obliterate orifices of lumbar and middle sacral arteries. Obstruction of these arteries causes ischemia in the lumbar spine and may result in back symptoms and disc degeneration. METHODS: MR aortography and cholesterol blood tests were performed on 51 patients with long-term lower back pain without specific findings (i.e., spinal or nerve root compression) in regular lumbar MR images. The patients ranged from 35 to 70 years of age (mean age, 56 years). Serum cholesterol and low-density lipoprotein (LDL) cholesterol levels were measured. To assess symptoms and disability NASS low back Outcome Instrument was used. RESULTS: Twenty-nine (78%) of 37 men and 11 (77%) of 14 women showed occluded lumbar and/or middle sacral arteries. The prevalence of occluded arteries was 2.5 times more than in subjects of corresponding age group in a Finnish necropsy material. Twenty-three (62%) men and seven (50%) women had significant disc degeneration. Disc degeneration was associated with occluded lumbar/middle sacral arteries (P = 0.035). Patients with occluded arteries or significant disc degeneration did not complain more severe symptoms than those without, whereas patients with above normal serum LDL cholesterol scored higher in neurogenic symptoms (P = 0.031) and complained more often severe pain (P = 0.049) than those with normal LDL cholesterol. CONCLUSIONS: The study indicates that lumbar and middle sacral arteries are often occluded in patients with nonspecific long-term lower back pain. Occlusion of these arteries may also be associated with disc degeneration.",
"title": "MR aortography and serum cholesterol levels in patients with long-term nonspecific lower back pain."
},
{
"docid": "MED-1532",
"text": "Although substantial nutrition transition, characterized by an increased intake of energy, animal fat, and red meats, has occurred during the last several decades in East Asia, few studies have systematically evaluated temporal trends in cancer incidence or mortality among populations in this area. Therefore, we sought to investigate this question with tremendous public health implications. Data on mortality rates of cancers of the breast, colon, prostate, esophagus, and stomach for China (1988-2000), Hong Kong (1960-2006), Japan (1950-2006), Korea (1985-2006), and Singapore (1963-2006) were obtained from WHO. Joinpoint regression was used to investigate trends in mortality of these cancers. A remarkable increase in mortality rates of breast, colon, and prostate cancers and a precipitous decrease in those of esophageal and stomach cancers have been observed in selected countries (except breast cancer in Hong Kong) during the study periods. For example, the annual percentage increase in breast cancer mortality was 5.5% (95% confidence interval: 3.8, 7.3%) for the period 1985-1993 in Korea, and mortality rates for prostate cancer significantly increased by 3.2% (95% confidence interval: 3.0, 3.3%) per year from 1958 to 1993 in Japan. These changes in cancer mortality lagged ∼ 10 years behind the inception of the nutrition transition toward a westernized diet in selected countries or regions. There have been striking changes in mortality rates of breast, colon, prostate, esophageal, and stomach cancers in East Asia during the last several decades, which may be at least in part attributable to the concurrent nutrition transition.",
"title": "Trends in mortality from cancers of the breast, colon, prostate, esophagus, and stomach in East Asia: role of nutrition transition."
},
{
"docid": "MED-3137",
"text": "A longstanding goal of dietary surveillance has been to estimate the proportion of the population with intakes above or below a target, such as a recommended level of intake. However, until now, statistical methods for assessing the alignment of food intakes with recommendations have been lacking. The purposes of this study were to demonstrate the National Cancer Institute’s method of estimating the distribution of usual intake of foods and determine the proportion of the U.S. population who does not meet federal dietary recommendations. Data were obtained from the 2001–2004 NHANES for 16,338 persons, aged 2 y and older. Quantities of foods reported on 24-h recalls were translated into amounts of various food groups using the MyPyramid Equivalents Database. Usual dietary intake distributions were modeled, accounting for sequence effect, weekend/weekday effect, sex, age, poverty income ratio, and race/ethnicity. The majority of the population did not meet recommendations for all of the nutrient-rich food groups, except total grains and meat and beans. Concomitantly, overconsumption of energy from solid fats, added sugars, and alcoholic beverages (“empty calories”) was ubiquitous. Over 80% of persons age ≥71 y and over 90% of all other sex-age groups had intakes of empty calories that exceeded the discretionary calorie allowances. In conclusion, nearly the entire U.S. population consumes a diet that is not on par with recommendations. These findings add another piece to the rather disturbing picture that is emerging of a nation’s diet in crisis.",
"title": "Americans Do Not Meet Federal Dietary Recommendations"
},
{
"docid": "MED-1405",
"text": "Background Polyphenols may lower the risk of cardiovascular disease (CVD) and other chronic diseases due to their antioxidant and anti-inflammatory properties, as well as their beneficial effects on blood pressure, lipids and insulin resistance. However, no previous epidemiological studies have evaluated the relationship between the intake of total polyphenols intake and polyphenol subclasses with overall mortality. Our aim was to evaluate whether polyphenol intake is associated with all-cause mortality in subjects at high cardiovascular risk. Methods We used data from the PREDIMED study, a 7,447-participant, parallel-group, randomized, multicenter, controlled five-year feeding trial aimed at assessing the effects of the Mediterranean Diet in primary prevention of cardiovascular disease. Polyphenol intake was calculated by matching food consumption data from repeated food frequency questionnaires (FFQ) with the Phenol-Explorer database on the polyphenol content of each reported food. Hazard ratios (HR) and 95% confidence intervals (CI) between polyphenol intake and mortality were estimated using time-dependent Cox proportional hazard models. Results Over an average of 4.8 years of follow-up, we observed 327 deaths. After multivariate adjustment, we found a 37% relative reduction in all-cause mortality comparing the highest versus the lowest quintiles of total polyphenol intake (hazard ratio (HR) = 0.63; 95% CI 0.41 to 0.97; P for trend = 0.12). Among the polyphenol subclasses, stilbenes and lignans were significantly associated with reduced all-cause mortality (HR =0.48; 95% CI 0.25 to 0.91; P for trend = 0.04 and HR = 0.60; 95% CI 0.37 to 0.97; P for trend = 0.03, respectively), with no significant associations apparent in the rest (flavonoids or phenolic acids). Conclusions Among high-risk subjects, those who reported a high polyphenol intake, especially of stilbenes and lignans, showed a reduced risk of overall mortality compared to those with lower intakes. These results may be useful to determine optimal polyphenol intake or specific food sources of polyphenols that may reduce the risk of all-cause mortality. Clinical trial registration ISRCTN35739639.",
"title": "Polyphenol intake and mortality risk: a re-analysis of the PREDIMED trial"
},
{
"docid": "MED-2940",
"text": "In the past 3 decades, the total number of CT scans performed has grown exponentially. In 2007, > 70 million CT scans were performed in the United States. CT scan studies of the chest comprise a large portion of the CT scans performed today because the technology has transformed the management of common chest diseases, including pulmonary embolism and coronary artery disease. As the number of studies performed yearly increases, a growing fraction of the population is exposed to low-dose ionizing radiation from CT scan. Data extrapolated from atomic bomb survivors and other populations exposed to low-dose ionizing radiation suggest that CT scan-associated radiation may increase an individual's lifetime risk of developing cancer. This finding, however, is not incontrovertible. Because this topic has recently attracted the attention of both the scientific community and the general public, it has become increasingly important for physicians to understand the cancer risk associated with CT scan and be capable of engaging in productive dialogue with patients. This article reviews the current literature on the public health debate surrounding CT scan and cancer risk, quantifies radiation doses associated with specific studies, and describes efforts to reduce population-wide CT scan-associated radiation exposure. CT scan examinations of the chest, including CT scan pulmonary and coronary angiography, high-resolution CT scan, low-dose lung cancer screening, and triple rule-out CT scan, are specifically considered.",
"title": "Radiation and chest CT scan examinations: what do we know?"
},
{
"docid": "MED-3444",
"text": "Research on the relationship between iodine exposure and thyroid cancer risk is limited, and the findings are inconclusive. In most studies, fish/shellfish consumption has been used as a proxy measure of iodine exposure. The present study extends this research by quantifying dietary iodine exposure as well as incorporating a biomarker of long-term (1 year) exposure, i.e., from toenail clippings. This study is conducted in a multiethnic population with a wide variation in thyroid cancer incidence rates and substantial diversity in exposure. Women, ages 20-74, residing in the San Francisco Bay Area and diagnosed with thyroid cancer between 1995 and 1998 (1992-1998 for Asian women) were compared with women selected from the general population via random digit dialing. Interviews were conducted in six languages with 608 cases and 558 controls. The established risk factors for thyroid cancer were found to increase risk in this population: radiation to the head/neck [odds ratio (OR), 2.3; 95% confidence interval (CI), 0.97-5.5]; history of goiter/nodules (OR, 3.7; 95% CI, 2.5-5.6); and a family history of proliferative thyroid disease (OR, 2.5; 95% CI, 1.6-3.8). Contrary to our hypothesis, increased dietary iodine, most likely related to the use of multivitamin pills, was associated with a reduced risk of papillary thyroid cancer. This risk reduction was observed in \"low-risk\" women (i.e., women without any of the three established risk factors noted above; OR, 0.53; 95% CI, 0.33-0.85) but not in \"high-risk\" women, among whom a slight elevation in risk was seen (OR, 1.4; 95% CI, 0.56-3.4). However, no association with risk was observed in either group when the biomarker of exposure was evaluated. In addition, no ethnic differences in risk were observed. The authors conclude that iodine exposure appears to have, at most, a weak effect on the risk of papillary thyroid cancer.",
"title": "Iodine and thyroid cancer risk among women in a multiethnic population: the Bay Area Thyroid Cancer Study."
},
{
"docid": "MED-1529",
"text": "BACKGROUND: Few previous prospective studies have examined differences in incident ischemic heart disease (IHD) risk between vegetarians and nonvegetarians. OBJECTIVE: The objective was to examine the association of a vegetarian diet with risk of incident (nonfatal and fatal) IHD. DESIGN: A total of 44,561 men and women living in England and Scotland who were enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Oxford study, of whom 34% consumed a vegetarian diet at baseline, were part of the analysis. Incident cases of IHD were identified through linkage with hospital records and death certificates. Serum lipids and blood pressure measurements were available for 1519 non cases, who were matched to IHD cases by sex and age. IHD risk by vegetarian status was estimated by using multivariate Cox proportional hazards models. RESULTS: After an average follow-up of 11.6 y, there were 1235 IHD cases (1066 hospital admissions and 169 deaths). Compared with nonvegetarians, vegetarians had a lower mean BMI [in kg/m(2); -1.2 (95% CI: -1.3, -1.1)], non-HDL-cholesterol concentration [-0.45 (95% CI: -0.60, -0.30) mmol/L], and systolic blood pressure [-3.3 (95% CI: -5.9, -0.7) mm Hg]. Vegetarians had a 32% lower risk (HR: 0.68; 95% CI: 0.58, 0.81) of IHD than did nonvegetarians, which was only slightly attenuated after adjustment for BMI and did not differ materially by sex, age, BMI, smoking, or the presence of IHD risk factors. CONCLUSION: Consuming a vegetarian diet was associated with lower IHD risk, a finding that is probably mediated by differences in non-HDL cholesterol, and systolic blood pressure.",
"title": "Risk of hospitalization or death from ischemic heart disease among British vegetarians and nonvegetarians: results from the EPIC-Oxford cohort study."
},
{
"docid": "MED-2807",
"text": "In a previous three-month study of Meriva, a proprietary curcumin-phosphatidylcholine phytosome complex, decreased joint pain and improvement in joint function were observed in 50 osteoarthritis (OA) patients. Since OA is a chronic condition requiring prolonged treatment, the long-term efficacy and safety of Meriva were investigated in a longer (eight months) study involving 100 OA patients. The clinical end points (Western Ontario and McMaster Universities [WOMAC] score, Karnofsky Performance Scale Index, and treadmill walking performance) were complemented by the evaluation of a series of inflammatory markers (interleukin [IL]-1beta, IL-6, soluble CD40 ligand [sCD40L], soluble vascular cell adhesion molecule (sVCAM)-1, and erythrocyte sedimentation rate [ESR]). This represents the most ambitious attempt, to date, to evaluate the clinical efficacy and safety of curcumin as an anti-inflammatory agent. Significant improvements of both the clinical and biochemical end points were observed for Meriva compared to the control group. This, coupled with an excellent tolerability, suggests that Meriva is worth considering for the long-term complementary management of osteoarthritis.",
"title": "Efficacy and safety of Meriva®, a curcumin-phosphatidylcholine complex, during extended administration in osteoarthritis patients."
},
{
"docid": "MED-2578",
"text": "The incidence of colonic cancer differs widely between various human populations. It has been suggested that dietary fiber content is of utmost importance and is inversely related to the occurrence of colonic cancer. However, high-fiber diets are not always correlated with low frequency of colonic cancer, suggesting the involvement of additional dietary constituents. Inositol hexaphosphate (phytic acid) is an abundant plant seed component present in many, but not all, fiber-rich diets. The authors have found that phytic acid is a potent inhibitor of iron-mediated generation of the hazardous oxidant, hydroxyl radical. Herein, the authors propose that inhibition of intracolonic hydroxyl radical generation, via the chelation of reactive iron by phytic acid, may help explain the suppression of colonic carcinogenesis and other inflammatory bowel diseases by diets rich in phytic acid.",
"title": "Dietary suppression of colonic cancer. Fiber or phytate?"
},
{
"docid": "MED-3000",
"text": "An increased risk for colorectal cancer has been consistently reported for long-time consumption of cooked and processed red meat. This has frequently been attributed to chemical carcinogens arising during the cooking process of meat. Long-time fish or poultry consumption apparently does not increase the risk, although similar or higher concentrations of chemical carcinogens were recorded in their preparation for consumption. The geographic epidemiology of colorectal cancer seems to correspond to regions with a high rate of beef consumption. Countries with a virtual absence of beef in the diet (India) or where preferably lamb or goat meat is consumed (several Arabic countries) reveal low rates of colorectal cancer. In China, pork consumption has a long tradition, with an intermediate colorectal cancer rate. In Japan and Korea, large scale beef and pork imports started after World War II or after the Korean War. A steep rise in colorectal cancer incidence was noted after 1970 in Japan and 1990 in Korea. The consumption of undercooked beef (e.g., shabu-shabu, Korean yukhoe and Japanese yukke) became very popular in both countries. The available data are compatible with the interpretation that a specific beef factor, suspected to be one or more thermoresistant potentially oncogenic bovine viruses (e.g., polyoma-, papilloma- or possibly single-stranded DNA viruses) may contaminate beef preparations and lead to latent infections in the colorectal tract. Preceding, concomitant or subsequent exposure to chemical carcinogens arising during cooking procedures should result in increased risk for colorectal cancer synergistic with these infections. Copyright © 2011 UICC.",
"title": "Red meat consumption and cancer: reasons to suspect involvement of bovine infectious factors in colorectal cancer."
},
{
"docid": "MED-3441",
"text": "As modern lifestyles and new feeding habits settle in the world, noncommunicable diseases (NCDs) have evolved to be major causes of disability in developing as well as developed countries. As a concomitant effect, there is a growing interest in natural, healthy food and an increasing awareness of risk factors and determinants of disease. This chapter describes some nutritional facts about seaweeds, which have been used as food since ancient times in China, Japan, Egypt, and India and comments on the potential utilization of marine algae as functional foods. This concept and the description of metabolic syndrome are used as a basis to comprehension of seaweeds against two dreadful illnesses of our times: high blood pressure and cancer. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "Marine edible algae as disease preventers."
},
{
"docid": "MED-2722",
"text": "Background Obesity and physical inactivity are associated with several chronic conditions, increased medical care costs, and premature death. Methods We used the Behavioral Risk Factor Surveillance System (BRFSS), a state-based random-digit telephone survey that covers the majority of United States counties, and the National Health and Nutrition Examination Survey (NHANES), a nationally representative sample of the US civilian noninstitutionalized population. About 3.7 million adults aged 20 years or older participated in the BRFSS from 2000 to 2011, and 30,000 adults aged 20 or older participated in NHANES from 1999 to 2010. We calculated body mass index (BMI) from self-reported weight and height in the BRFSS and adjusted for self-reporting bias using NHANES. We calculated self-reported physical activity—both any physical activity and physical activity meeting recommended levels—from self-reported data in the BRFSS. We used validated small area estimation methods to generate estimates of obesity and physical activity prevalence for each county annually for 2001 to 2011. Results Our results showed an increase in the prevalence of sufficient physical activity from 2001 to 2009. Levels were generally higher in men than in women, but increases were greater in women than men. Counties in Kentucky, Florida, Georgia, and California reported the largest gains. This increase in level of activity was matched by an increase in obesity in almost all counties during the same time period. There was a low correlation between level of physical activity and obesity in US counties. From 2001 to 2009, controlling for changes in poverty, unemployment, number of doctors per 100,000 population, percent rural, and baseline levels of obesity, for every 1 percentage point increase in physical activity prevalence, obesity prevalence was 0.11 percentage points lower. Conclusions Our study showed that increased physical activity alone has a small impact on obesity prevalence at the county level in the US. Indeed, the rise in physical activity levels will have a positive independent impact on the health of Americans as it will reduce the burden of cardiovascular diseases and diabetes. Other changes such as reduction in caloric intake are likely needed to curb the obesity epidemic and its burden.",
"title": "Prevalence of physical activity and obesity in US counties, 2001–2011: a road map for action"
},
{
"docid": "MED-3274",
"text": "Objective To determine whether dogs can be trained to identify people with bladder cancer on the basis of urine odour more successfully than would be expected by chance alone. Design Experimental, “proof of principle” study in which six dogs were trained to discriminate between urine from patients with bladder cancer and urine from diseased and healthy controls and then evaluated in tests requiring the selection of one bladder cancer urine sample from six controls. Participants 36 male and female patients (age range 48-90 years) presenting with new or recurrent transitional cell carcinoma of the bladder (27 samples used for training; 9 used for formal testing); 108 male and female controls (diseased and healthy, age range 18-85 years—54 samples used in training; 54 used for testing). Main outcome measure Mean proportion of successes per dog achieved during evaluation, compared with an expected value of 1 in 7 (14%). Results Taken as a group, the dogs correctly selected urine from patients with bladder cancer on 22 out of 54 occasions. This gave a mean success rate of 41% (95% confidence intervals 23% to 58% under assumptions of normality, 26% to 52% using bootstrap methods), compared with 14% expected by chance alone. Multivariate analysis suggested that the dogs' capacity to recognise a characteristic bladder cancer odour was independent of other chemical aspects of the urine detectable by urinalysis. Conclusions Dogs can be trained to distinguish patients with bladder cancer on the basis of urine odour more successfully than would be expected by chance alone. This suggests that tumour related volatile compounds are present in urine, imparting a characteristic odour signature distinct from those associated with secondary effects of the tumour, such as bleeding, inflammation, and infection.",
"title": "Olfactory detection of human bladder cancer by dogs: proof of principle study"
},
{
"docid": "MED-1950",
"text": "Several studies have found associations between microbial infections during pregnancy and preterm delivery (PTD). We investigated the influence of food with antimicrobial and prebiotic components on the risk of spontaneous PTD. A literature search identified microbes associated with spontaneous PTD. Subsequently, 2 main food types (alliums and dried fruits) were identified to contain antimicrobial components that affect the microbes associated with spontaneous PTD; they also contained dietary fibers recognized as prebiotics. We investigated intake in 18,888 women in the Norwegian Mother and Child Cohort (MoBa), of whom 950 (5%) underwent spontaneous PTD (<37 gestational weeks). Alliums (garlic, onion, leek, and spring onion) [OR: 0.82 (95% CI: 0.72, 0.94), P = 0.005] and dried fruits (raisins, apricots, prunes, figs, and dates) [OR: 0.82 (95% CI: 0.72, 0.94); P = 0.005] were associated with a decreased risk of spontaneous PTD. Intake of alliums was related to a more pronounced risk reduction in early spontaneous PTD (gestational weeks 28–31) [OR: 0.39 (95% CI: 0.19, 0.80)]. The strongest association in this group was with garlic [OR: 0.47 (95% CI: 0.25–0.89)], followed by cooked onions. Intake of dried fruits showed an association with preterm prelabor rupture of membranes (PPROM) [OR: 0.74 (95% CI: 0.65, 0.95)]; the strongest association in this group was with raisins [OR: 0.71 (95% CI: 0.56, 0.92)]. The strongest association with PPROM in the allium group was with garlic [OR: 0.74 (95% CI: 0.56, 0.97)]. In conclusion, intake of food with antimicrobial and prebiotic compounds may be of importance to reduce the risk of spontaneous PTD. In particular, garlic was associated with overall lower risk of spontaneous PTD. Dried fruits, especially raisins, were associated with reduced risk of PPROM.",
"title": "Intakes of Garlic and Dried Fruits Are Associated with Lower Risk of Spontaneous Preterm Delivery"
},
{
"docid": "MED-2966",
"text": "OBJECTIVE: Determine 1) if consumption of a meal of different fruits or berries increases plasma hydrophilic (H-) or lipophilic (L-) antioxidant capacity (AOC) measured as Oxygen Radical Absorbance Capacity (ORAC(FL)); 2) if including macronutrients in the meal alters postprandial changes in AOC; and 3) if preliminary recommendations can be developed for antioxidant intake. METHODS: Changes in plasma AOC following consumption of a single meal of berries/fruits (blueberry, dried plum, dried plum juice, grape, cherry, kiwifruit and strawberry) were studied in 5 clinical trials with 6-10 subjects per experiment. In two studies with blueberry or grape, additional macronutrients (carbohydrate, fat, protein) were included in the control and treatment meals. Blood samples collected before and after the meal were analyzed for AOC. RESULTS: Consumption of dried plums or dried plum juice did not alter either the H- or L-AOC area under the curve (AUC). Consumption of blueberry in 2 studies and of mixed grape powder [12.5 (Study #1), 39.9 (Study #4) and 8.6 (Study #5) mmole Trolox Equivalents (TE) AOC, respectively] increased hydrophilic AOC AUC. L-AOC increased following a meal of blueberry containing 12.5 mmole TE AOC (Study #1). Consumption of 280 g of cherries (4.5 mmol TE AOC) increased plasma L-AOC but not H-AOC. The AOC in the control groups in which additional macronutrients (Studies #4 and #5) were added decreased from the postprandial baseline AOC measurement. CONCLUSION: We have demonstrated that consumption of certain berries and fruits such as blueberries, mixed grape and kiwifruit, was associated with increased plasma AOC in the postprandial state and consumption of an energy source of macronutrients containing no antioxidants was associated with a decline in plasma AOC. However, without further long term clinical studies, one cannot necessarily translate increased plasma AOC into a potential decreased risk of chronic degenerative disease. Preliminary estimates of antioxidant needs based upon energy intake were developed. Consumption of high antioxidant foods with each meal is recommended in order to prevent periods of postprandial oxidative stress.",
"title": "Plasma antioxidant capacity changes following a meal as a measure of the ability of a food to alter in vivo antioxidant status."
},
{
"docid": "MED-3110",
"text": "Leflunomide, flutamide, nimodipine, mexiletine, sulindac, tranilast, 4-hydroxytamoxifen, and omeprazole are pharmaceuticals previously characterized as aryl hydrocarbon receptor (AHR) agonists in various cell lines and animal models. In this study, the eight AHR-active pharmaceuticals were investigated in highly aggressive aryl hydrocarbon (Ah)-responsive BT474 and MDA-MB-468 breast cancer cell lines, and their effects on AHR protein, CYP1A1 (protein and mRNA), CYP1B1 (mRNA), and cell migration were determined. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) was used as a positive control. The AHR agonist activities of the pharmaceuticals depended on structure, response, and cell context. Most compounds induced one or more AHR-mediated responses in BT474 cells, whereas in Ah-responsive MDA-MB-468 cells effects of the AHR-active pharmaceuticals were highly variable. 4-Hydroxytamoxifen, mexiletine, and tranilast did not induce CYP1A1 in MDA-MB-468 cells; moreover, in combination with TCDD, mexiletine was a potent AHR antagonist, tranilast was a partial antagonist, and 4-hydroxytamoxifen also exhibited some AHR antagonist activity. Omeprazole and, to a lesser extent, sulindac and leflunomide were full and partial AHR agonists, respectively, in both breast cancer cell lines. These data indicate that the AHR-active pharmaceuticals are selective AHR modulators, and applications of these drugs for targeting the AHR must be confirmed by studies using the most relevant cell context.",
"title": "Aryl Hydrocarbon Receptor (AHR)-Active Pharmaceuticals Are Selective AHR Modulators in MDA-MB-468 and BT474 Breast Cancer Cells"
},
{
"docid": "MED-2517",
"text": "Many experts in the biology of ageing believe that pharmacological interventions to slow ageing are a matter of ‘when’ rather than ‘if’. A leading target for such interventions is the nutrient response pathway defined by the mechanistic target of rapamycin (mTOR). Inhibition of this pathway extends lifespan in model organisms and confers protection against a growing list of age-related pathologies. Characterized inhibitors of this pathway are already clinically approved, and others are under development. Although adverse side effects currently preclude use in otherwise healthy individuals, drugs that target the mTOR pathway could one day become widely used to slow ageing and reduce age-related pathologies in humans.",
"title": "mTOR is a key modulator of ageing and age-related disease"
},
{
"docid": "MED-2570",
"text": "The functional properties, including antioxidant and chemopreventative capacities as well as the inhibitory effects on angiotensin-converting enzyme (ACE), α-glucosidase and pancreatic lipase, of three Australian-grown faba bean genotypes (Nura, Rossa and TF(Ic*As)*483/13) were investigated using an array of in vitro assays. Chromatograms of on-line post column derivatisation assay coupled with HPLC revealed the existence of active phenolics (hump) in the coloured genotypes, which was lacking in the white-coloured breeding line, TF(Ic*As)*483/13. Roasting reduced the phenolic content, and diminished antioxidant activity by 10-40 % as measured by the reagent-based assays (diphenylpicrylhydrazyl, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) and oxygen radical absorbance capacity) in all genotypes. Cell culture-based antioxidant activity assay (cellular antioxidant activity) showed an increase of activity in the coloured genotypes after roasting. Faba bean extracts demonstrated cellular protection ability against H₂O₂-induced DNA damage (assessed using RAW264.7 cells), and inhibited the proliferation of all human cancer cell lines (BL13, AGS, Hep G2 and HT-29) evaluated. However, the effect of faba bean extracts on the non-transformed human cells (CCD-18Co) was negligible. Flow cytometric analyses showed that faba bean extracts successfully induced apoptosis of HL-60 (acute promyelocytic leukaemia) cells. The faba bean extracts also exhibited ACE, α-glucosidase and pancreatic lipase inhibitory activities. Overall, extracts from Nura (buff-coloured) and Rossa (red-coloured) were comparable, while TF(Ic*As)*483/13 (white-coloured) contained the lowest phenolic content and exhibited the least antioxidant and enzyme inhibition activities. These results are important to promote the utilisation of faba beans in human diets for various health benefits.",
"title": "In vitro investigations of the potential health benefits of Australian-grown faba beans (Vicia faba L.): chemopreventative capacity and inhibitory ..."
},
{
"docid": "MED-2212",
"text": "With the republication of Grant (18), the first paper providing epidemiologic evidence linking diet to the development of Alzheimer's disease (AD), it is an appropriate time to review the findings and hypotheses therein in light of the subsequent literature. The main findings, that dietary fat and energy in old age are high risk factors, while fish and cereals are risk-reduction factors, have been supported in various recent epidemiologic studies. Diet contributes to the development of AD through modulating oxidative stress and inflammation, which is also linked to oxidative stress, but may also arise from series 2 prostaglandins. Thus, as one ages, dietary modifications and additional supplements designed to reduce free radical production and inflammation provide a significant measure of reduction in risk for the development of AD.",
"title": "Dietary links to Alzheimer's disease: 1999 update."
},
{
"docid": "MED-3143",
"text": "BACKGROUND: Olestra is a nonabsorbable, energy-free fat substitute. Because it is not absorbed, it may cause digestive symptoms when consumed in large amounts. OBJECTIVE: To compare the frequency and impact of gastrointestinal symptoms in adults and children who freely consume snacks containing olestra or regular snacks in the home. DESIGN: 6-week, double-blind, randomized, parallel, placebo-controlled trial. SETTING: General community. PARTICIPANTS: 3181 volunteers 2 to 89 years of age. INTERVENTION: Households received identical packages labeled as containing olestra corn or potato chips. These packages contained either olestra or regular chips (control). MEASUREMENT: Gastrointestinal symptoms and their impact on daily activities were reported in a daily record. RESULTS: At least one gastrointestinal symptom was reported by 619 of 1620 (38.2%) persons in the olestra group and 576 of 1561 (36.9%) controls (difference, 1.3 percentage points [95% CI, -3.6 to 6.2 percentage points]; P = 0.60). In general, the groups did not differ significantly in the proportion of participants who reported individual gastrointestinal symptoms; however, more controls reported nausea (8.4% compared with 5.7%; difference, -2.7 percentage points [CI, -4.9 to -0.4 percentage points]; P = 0.02). The only difference between groups for the mean numbers of days on which symptoms were reported was that participants in the olestra group had 1 more symptom-day of more frequent bowel movements than did controls (3.7 symptom-days compared with 2.8 symptom days; difference, 0.9 symptom-days [CI, 0.1 to 1.8 symptom-days]; P = 0.04). The groups did not differ in the impact of symptoms on daily activities. CONCLUSIONS: Clinically meaningful or bothersome gastrointestinal effects are not associated with unregulated consumption of olestra corn and potato chips in the home.",
"title": "Gastrointestinal symptoms in 3181 volunteers ingesting snack foods containing olestra or triglycerides. A 6-week randomized, placebo-controlled trial."
},
{
"docid": "MED-2115",
"text": "Dietary PUFA, mainly those of the n-3 family, are known to play essential roles in the maintenance of energy balance and in the reduction of body fat deposition through the upregulation of mitochondrial uncoupling that is the main source of reactive oxygen species. We hypothesized that rat supplementation with raw donkey's milk (DM), characterized by low-fat content and higher n3:n6 ratio, may affect energy balance, lipid metabolism, and prooxidant status as compared to animals treated with cow's milk. In the present study, the effects of drinking raw DM (for 4 weeks) on energy balance, lipid metabolism, antiinflammatory, and antioxidant/detoxifying defences was compared to that produced by rat intake of an iso-energetic amount of raw cow's milk. The hypolipidemic effect produced by DM paralleled with the enhanced mitochondrial activity/proton leakage and with the increased activity or expression of mitochondrial markers namely, carnitine palmitoyl transferase and uncoupling protein 2. The association of decreased energy efficiency with reduced proinflammatory signs (TNF-α and LPS levels) with the significant increase antioxidant (total thiols) and detoxifying enzyme activities (glutathione-S-transferase NADH quinone oxidoreductase) in DM-treated animals, indicated that beneficial effects were attributable, at least in part, to the activation of nuclear factor 2 erythroid-related factor 2 pathway. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",
"title": "Diet supplementation with donkey milk upregulates liver mitochondrial uncoupling, reduces energy efficiency and improves antioxidant and antiinflam..."
},
{
"docid": "MED-2184",
"text": "Objectives. We examined the effects of state-level unemployment rates during the recession of 2008 on patterns of home food preparation and away-from-home (AFH) eating among low-income and minority populations. Methods. We analyzed pooled cross-sectional data on 118 635 adults aged 18 years or older who took part in the American Time Use Study. Multinomial logistic regression models stratified by gender were used to evaluate the associations between state-level unemployment, poverty, race/ethnicity, and time spent cooking, and log binomial regression was used to assess respondents’ AFH consumption patterns. Results. High state-level unemployment was associated with only trivial increases in respondents’ cooking patterns and virtually no change in their AFH eating patterns. Low-income and racial/ethnic minority groups were not disproportionately affected by the recession. Conclusions. Even during a major economic downturn, US adults are resistant to food-related behavior change. More work is needed to understand whether this reluctance to change is attributable to time limits, lack of knowledge or skill related to food preparation, or lack of access to fresh produce and raw ingredients.",
"title": "Resistant to the Recession: Low-Income Adults’ Maintenance of Cooking and Away-From-Home Eating Behaviors During Times of Economic Turbulence"
},
{
"docid": "MED-3273",
"text": "Recent studies confirm that dietary methionine restriction increases both mean and maximal lifespan in rats and mice, achieving \"aging retardant\" effects very similar to those of caloric restriction, including a suppression of mitochondrial superoxide generation. Although voluntary caloric restriction is never likely to gain much popularity as a pro-longevity strategy for humans, it may be more feasible to achieve moderate methionine restriction, in light of the fact that vegan diets tend to be relatively low in this amino acid. Plant proteins - especially those derived from legumes or nuts - tend to be lower in methionine than animal proteins. Furthermore, the total protein content of vegan diets, as a function of calorie content, tends to be lower than that of omnivore diets, and plant protein has somewhat lower bioavailability than animal protein. Whole-food vegan diets that moderate bean and soy intake, while including ample amounts of fruit and wine or beer, can be quite low in methionine, while supplying abundant nutrition for health (assuming concurrent B12 supplementation). Furthermore, low-fat vegan diets, coupled with exercise training, can be expected to promote longevity by decreasing systemic levels of insulin and free IGF-I; the latter effect would be amplified by methionine restriction - though it is not clear whether IGF-I down-regulation is the sole basis for the impact of low-methionine diets on longevity in rodents.",
"title": "The low-methionine content of vegan diets may make methionine restriction feasible as a life extension strategy."
},
{
"docid": "MED-2971",
"text": "Diabetes mellitus is associated with increased ROS generation, oxidative injury and obesity. To elucidate the relationship between nutrition and ROS generation, we have investigated the effect of glucose challenge on ROS generation by leucocytes, p47phox protein, a key protein in the enzyme NADPH oxidase and alpha-tocopherol levels. Blood samples were drawn from 14 normal subjects prior to, at 1, 2 and 3 h following ingestion of 75 g glucose. ROS generation by polymorphonuclear leucocytes (PMNL) and mononuclear cells (MNC) increased to a peak of 244 +/- 42% and 233 +/- 34% of the basal respectively at 2h. The levels of p47phox in MNC homogenates increased significantly at 2 h and 3 h after glucose intake. alpha-Tocopherol levels decreased significantly at 1 h, 2 h and 3 h. We conclude that glucose intake stimulates ROS generation and p417phox of NADPH oxidase; increases oxidative load and causes a fall in alpha-tocopherol concentration.",
"title": "Glucose challenge stimulates reactive oxygen species (ROS) generation by leucocytes."
},
{
"docid": "MED-3876",
"text": "BACKGROUND: Chinese men have lower incidences of prostate cancer compared to men from Europe and North America. Asians consume large quantities of soya, a rich source of isoflavanoids phyto-oestrogens and have high plasma and urinary levels of these compounds. The mammalian lignans, enterolactone and enterodiol, are another group of weak plant oestrogens and are derived from seeds, cereals and grains. Vegetarians have high plasma and urinary concentrations of lignans. METHODS: The concentrations lignans and isoflavonic phyto-oestrogens were determined by gas chromatography-mass spectrometry (GC-MS) in plasma and prostatic fluid from Portuguese, Chinese and British men consuming their traditional diets. RESULTS: In prostatic fluid the mean concentrations of enterolactone were 31, 162 and 20.3 ng/ml for Hong Kong, Portugal and Britain respectively. Very high levels of enterolactone (> 600 ng/ml) were observed in the prostatic fluid of some of the men from Portugal. High concentrations of equol (3270 ng/ml) and daidzein (532 ng/ml) were found in a sample of prostatic fluid from Hong Kong. Higher mean levels of daidzein were observed in prostatic fluid from Hong Kong at 70 ng/ml, compared to 4.6 and 11.3 ng/ml in samples from Portugal and Britain respectively. Mean levels of daidzein were higher in the plasma samples from Hong Kong (31.3 ng/ml) compared to those from Portugal (1.3 ng/ml) and Britain (8.2 ng/ml). In general, the mean plasma concentrations of enterolactone from the three centres were similar, at 6.2, 3.9 and 3.9 ng/ml in samples from Hong Kong Portugal and Britain respectively. CONCLUSIONS: Higher concentrations of the isoflavanoid phyto-oestrogens, daidzein and equol, were found in the plasma and prostatic fluid of men from Hong Kong compared to those from Britain and Portugal. However, the levels of the lignan, enterolactone, were very much higher in prostatic fluid of Portuguese men. Isoflavanoids and lignans have many interesting properties and may, in part, be responsible for lower incidences of prostate cancer in men from Asia and also some Mediterranean countries. The isoflavanoids from soya, which are present in high concentrations in the prostatic fluid of Asian men, may be protective against prostate disease.",
"title": "Lignans and isoflavonoids in plasma and prostatic fluid in men: samples from Portugal, Hong Kong, and the United Kingdom."
},
{
"docid": "MED-3141",
"text": "OBJECTIVE: To evaluate the associations with chronic disease risk and mortality of the consequences of bean-free diets in Taiwanese adults with regard to gender. DESIGN: A sub-sample of the National Health Interview Survey (NHIS) in 2001 agreed to physical examination in the subsequent year. This group then took part in the Taiwanese Survey of Hyperglycaemia, Hyperlipidaemia and Hypertension (TwSHHH) in 2002. SETTING: Individual records were linked to the eventual death files from 2002 to 2008. SUBJECTS: Up to the end of 2008, a total of 2820 men and 2950 women were tracked by death registry over the 6·8 years of follow-up. RESULTS: Among 38,077 person-years, an average follow-up 6·5 years, 225 all-cause deaths were identified. Generalized linear models showed beans to be favourable for metabolic syndrome (other than for fasting glucose) in men; in women, beans were favourable for waist circumference and HbA1c. Cumulative logistic regression models for the effect of a bean-free diet on metabolic syndrome scores according to the Taiwanese-modified National Cholesterol Education Program-Adult Treatment Panel III (NCEP-tw) gave adjusted odds ratios of 1·83 in men and 1·45 in women. Cox regression models for the bean-free diet showed an increased hazard ratio for all-cause mortality among women (1·98, 95% CI 1·03, 3·81) but not men (1·28, 95% CI 0·76, 2·16). CONCLUSIONS: A bean-free diet may play a role in developing the metabolic syndrome in both genders, and is a significant predictor of all-cause mortality in Taiwanese women but not men.",
"title": "A bean-free diet increases the risk of all-cause mortality among Taiwanese women: the role of the metabolic syndrome."
},
{
"docid": "MED-2217",
"text": "OBJECTIVE: To determine the prevalence of AD and other dementias in a rural elderly Hindi-speaking population in Ballabgarh in northern India. DESIGN: The authors performed a community survey of a cohort of 5,126 individuals aged 55 years and older, 73.3% of whom were illiterate. Hindi cognitive and functional screening instruments, developed for and validated in this population, were used to screen the cohort. A total of 536 subjects (10.5%) who met operational criteria for cognitive and functional impairment and a random sample of 270 unimpaired control subjects (5.3%) underwent standardized clinical assessment for dementia using the Diagnostic and Statistical Manual of Mental Disorders-fourth edition diagnostic criteria, the Clinical Dementia Rating Scale (CDR), and National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable and possible AD. RESULTS: We found an overall prevalence rate of 0.84% (95% CI, 0.61 to 1.13) for all dementias with a CDR score of at least 0.5 in the population aged 55 years and older, and an overall prevalence rate of 1.36% (95% CI, 0.96 to 1.88) in the population aged 65 years and older. The overall prevalence rate for AD was 0.62% (95% CI, 0.43 to 0.88) in the population aged 55+ and 1.07% (95% CI, 0.72 to 1.53) in the population aged 65+. Greater age was associated significantly with higher prevalence of both AD and all dementias, but neither gender nor literacy was associated with prevalence. CONCLUSIONS: In this population, the prevalence of AD and other dementias was low, increased with age, and was not associated with gender or literacy. Possible explanations include low overall life expectancy, short survival with the disease, and low age-specific incidence potentially due to differences in the underlying distribution of risk and protective factors compared with populations with higher prevalence.",
"title": "Prevalence of Alzheimer's disease and other dementias in rural India: the Indo-US study."
},
{
"docid": "MED-2799",
"text": "Objective: To compare selected immunohistological features of inflammation in synovial tissue from patients with early and late osteoarthritis (OA). Methods: Synovial tissue samples were obtained from 10 patients with knee pain, normal radiographs, and arthroscopic manifestations of OA (early OA), and from 15 patients with OA undergoing knee joint arthroplasty (late OA). Conventional immunohistochemical techniques were used to measure microscopic manifestations of inflammation. The inflammatory cell infiltrate, blood vessel formation, and angiogenic factors, NF-κB activation, expression of tumour necrosis factor α (TNFα) and interleukin 1ß (IL1ß), and the presence of cyclo-oxygenase (COX)-1 and COX-2 were quantified. Fibroblast-like synoviocytes (FLS) were isolated from early and late OA tissue samples to compare in vitro production of prostaglandin E2 (PGE2) Results: Synovial tissue from patients with early OA demonstrated significantly greater CD4+ (p = 0.017) and CD68+ (p<0.001) cell infiltration, blood vessel formation (p = 0.01), vascular endothelial growth factor (p = 0.001), and intercellular adhesion molecule-1 expression (p<0.001). Numbers of cells producing TNFα and IL1ß were also significantly greater in early OA (p<0.001). Manifestations of inflammation in early OA were associated with increased expression of the NF-κB1 (p<0.001) and RelA (p = 0.015) subunits, and with increased COX-2 expression (p = 0.04). Cytokine-induced PGE2 production by cultured FLS was similar in both groups. Conclusion: Increased mononuclear cell infiltration and overexpression of mediators of inflammation were seen in early OA, compared with late OA. Isolated FLS were functionally similar in both groups, consistent with microenvironmental differences in the synovial tissue during different phases of OA. These observations may have important therapeutic implications for some patients during the early evolution of OA.",
"title": "Synovial tissue inflammation in early and late osteoarthritis"
},
{
"docid": "MED-3794",
"text": "OBJECTIVE: To test the hypothesis that a low-fat, vegetarian diet reduces dysmenorrhea and premenstrual symptoms by its effect on serum sex-hormone binding globulin concentration and estrogen activity. METHODS: In a crossover design, 33 women followed a low-fat, vegetarian diet for two menstrual cycles. For two additional cycles, they followed their customary diet while taking a supplement placebo pill. Dietary intake, serum sex-hormone binding globulin concentration, body weight, pain duration and intensity, and premenstrual symptoms were assessed during each study phase. RESULTS: Mean (+/- standard deviation [SD]) serum sex-hormone binding globulin concentration was higher during the diet phase (46.7 +/- 23.6 nmol/L) than during the supplement phase (39.3 +/- 19.8 nmol/L, P < .001). Mean (+/- SD) body weight was lower during the diet (66.1 +/- 11.3 kg) compared with the supplement phase (67.9 +/- 12.1 kg, P < .001). Mean dysmenorrhea duration fell significantly from baseline (3.9 +/- 1.7 days) to diet phase (2.7 +/- 1.9 days) compared with change from baseline to supplement phase (3.6 +/- 1.7 days, P < .01). Pain intensity fell significantly during the diet phase, compared with baseline, for the worst, second-worst, and third-worst days, and mean durations of premenstrual concentration, behavioral change, and water retention symptoms were reduced significantly, compared with the supplement phase. CONCLUSION: A low-fat vegetarian diet was associated with increased serum sex-hormone binding globulin concentration and reductions in body weight, dysmenorrhea duration and intensity, and premenstrual symptom duration. The symptom effects might be mediated by dietary influences on estrogen activity.",
"title": "Diet and sex-hormone binding globulin, dysmenorrhea, and premenstrual symptoms."
},
{
"docid": "MED-2571",
"text": "Background Prospective, randomized, pilot clinical study was conducted to evaluate the beneficial effects of inositol hexaphosphate (IP6) + Inositol in breast cancer patients treated with adjuvant therapy. Patients and methods Patients with invasive ductal breast cancer where polychemotherapy was indicated were monitored in the period from 2005-2007. Fourteen patients in the same stage of ductal invasive breast cancer were involved in the study, divided in two randomized groups. One group was subjected to take IP6 + Inositol while the other group was taking placebo. In both groups of patients the same laboratory parameters were monitored. When the treatment was finished, all patients have filled questionnaires QLQ C30 and QLQ-BR23 to determine the quality of life. Results Patients receiving chemotherapy, along with IP6 + Inositol did not have cytopenia, drop in leukocyte and platelet counts. Red blood cell counts and tumor markers were unaltered in both groups. However, patients who took IP6 + Inositol had significantly better quality of life (p = 0.05) and functional status (p = 0.0003) and were able to perform their daily activities. Conclusion IP6 + Inositol as an adjunctive therapy is valuable help in ameliorating the side effects and preserving quality of life among the patients treated with chemotherapy.",
"title": "Efficacy of IP6 + inositol in the treatment of breast cancer patients receiving chemotherapy: prospective, randomized, pilot clinical study"
},
{
"docid": "MED-3281",
"text": "INTRODUCTION: Amino acid auxotrophy or the metabolic defect which renders cancer incapable of surviving under amino acid depleted conditions is being exploited and explored as a therapeutic against cancer. Early clinical data on asparagine- and arginine-depleting drugs have demonstrated low toxicity and efficacy in melanoma, hepatocellular carcinoma and acute lymphoblastic leukemia. Methionine auxotrophy is a novel niche currently under exploration for targeting certain cancers. AREAS COVERED: In this review we explore the discovery of methionine auxotrophy followed by in vitro, in vivo and patient data on targeting cancer with methionine depletion. We end with a small discussion on bioengineering, pegylation and red blood cell encapsulation as mechanisms for decreasing immunogenicity of methionine-depleting drugs. We hope to provide a platform for future pharmacology, toxicology and cytotoxicity studies with methionine depletion therapy and drugs. EXPERT OPINION: Although methionine auxotrophy seems as a viable target, extensive research addressing normal versus cancer cell toxicity needs to be conducted. Further research also needs to be conducted into the molecular mechanism associated with methionine depletion therapy. Finally, novel methods need to be developed to decrease the immunogenicity of methionine-depleting drugs, a current issue with protein therapeutics.",
"title": "Targeting methionine auxotrophy in cancer: discovery & exploration."
},
{
"docid": "MED-3696",
"text": "The authors assessed the association between moderate alcohol consumption and breast cancer risk in the Women's Health Study (United States, 1992-2004). During an average of 10 years of follow-up, 1,484 cases of total breast cancer (1,190 invasive and 294 in situ) were documented among 38,454 women who, at baseline, were free of cancer and cardiovascular disease and provided detailed dietary information, including alcohol consumption, for the preceding 12 months. Higher alcohol consumption was associated with a modest increase in breast cancer risk; the multivariable relative risks for > or =30 g/day of alcohol vs. none were 1.32 (95% confidence interval (CI): 0.96, 1.82) for total breast cancer and 1.43 (95% CI: 1.02, 2.02) for invasive breast cancer. An increased risk was limited to estrogen receptor (ER)- and progesterone receptor (PR)-positive tumors; the multivariable relative risks for an increment of 10 g/day of alcohol were 1.11 (95% CI: 1.03, 1.20) for ER+PR+ tumors (804 cases), 1.00 (95% CI: 0.81, 1.24) for ER+PR- tumors (125 cases), and 0.99 (95% CI: 0.82, 1.20) for ER-PR- tumors (167 cases). The association also seemed strongest among those taking postmenopausal hormones currently, but the test for interaction was not significant. The findings from this prospective study suggest that moderate alcohol consumption increases breast cancer risk.",
"title": "Alcohol consumption and breast cancer risk in the Women's Health Study."
},
{
"docid": "MED-3874",
"text": "Background Prostate cancer affects one-out-of-six men during their lifetime. Dietary factors are postulated to influence the development and progression of prostate cancer. Low-fat diets and flaxseed supplementation may offer potentially protective strategies. Methods We undertook a multi-site, randomized controlled trial to test the effects of low-fat and/or flaxseed-supplemented diets on the biology of the prostate and other biomarkers. Prostate cancer patients (n=161) scheduled at least 21 days before prostatectomy were randomly assigned to one of the following arms: 1) control (usual diet); 2) flaxseed-supplemented diet (30 g/day); 2) low-fat diet (<20% total energy); or 4) flaxseed-supplemented, low-fat diet. Blood was drawn at baseline and prior to surgery and analyzed for prostate specific antigen (PSA), sex hormone binding globulin, testosterone, insulin-like growth factor-1 and binding protein-3, c-reactive protein, and total and low density lipoprotein cholesterol. Tumors were assessed for proliferation (Ki-67, the primary endpoint) and apoptosis. Results Men were on protocol an average of 30 days. Proliferation rates were significantly lower (P < 0.002) among men assigned to the flaxseed arms. Median Ki-67 positive cells/total nuclei ratios (x100) were 1.66 (flaxseed-supplemented diet) and 1.50 (flaxseed-supplemented, low-fat diet) vs. 3.23 (control) and 2.56 (low-fat diet). No differences were observed between arms with regard to side effects, apoptosis, and most serological endpoints; however, men on low-fat diets experienced significant decreases in serum cholesterol (P=0.048). Conclusions Findings suggest that flaxseed is safe, and associated with biologic alterations that may be protective for prostate cancer. Data also further support low-fat diets to manage serum cholesterol.",
"title": "Flaxseed Supplementation (not Dietary Fat Restriction) Reduces Prostate Cancer Proliferation Rates in Men Presurgery"
},
{
"docid": "MED-1194",
"text": "Noncommunicable diseases (NCDs)--mainly cancers, cardiovascular diseases, diabetes, and chronic respiratory diseases--are responsible for about two-thirds of deaths worldwide, mostly in low- and middle-income countries. There is an urgent need for policies and strategies that prevent NCDs by reducing their major risk factors. Effective approaches for large-scale NCD prevention include comprehensive tobacco and alcohol control through taxes and regulation of sales and advertising; reducing dietary salt, unhealthy fats, and sugars through regulation and well-designed public education; increasing the consumption of fresh fruits and vegetables, healthy fats, and whole grains by lowering prices and improving availability; and implementing a universal, effective, and equitable primary-care system that reduces NCD risk factors, including cardiometabolic risk factors and infections that are precursors to NCDs, through clinical interventions.",
"title": "Can noncommunicable diseases be prevented? Lessons from studies of populations and individuals."
},
{
"docid": "MED-2944",
"text": "The need for consistent and current data describing the true incidence of SCA and/or SCD was highlighted during the most recent Sudden Cardiac Arrest Thought Leadership Alliance’s (SCATLA) Think Tank meeting of national experts with broad representation of key stakeholders including thought leaders and representatives from the American College of Cardiology, American Heart Association, and the Heart Rhythm Society. As such, to evaluate the true magnitude of this public health problem, we performed a systematic literature search in MEDLINE using the MeSH headings, “death, sudden” OR the terms “sudden cardiac death” OR “sudden cardiac arrest” OR “cardiac arrest” OR “cardiac death” OR “sudden death” OR “arrhythmic death.” Study selection criteria included peer-reviewed publications of primary data used to estimate SCD incidence in the U.S. We used Web of Science®’s Cited Reference Search to evaluate the impact of each primary estimate on the medical literature by determining the number of times each “primary source” has been cited. The estimated U.S. annual incidence of SCD varied widely from 180,000 to > 450,000 among 6 included studies. These different estimates were in part due to different data sources (with data age ranging from 1980 to 2007), definitions of SCD, case ascertainment criteria, methods of estimation/extrapolation, and sources of case ascertainment. The true incidence of SCA and/or SCD in the U.S. remains unclear with a wide range in the available estimates, which are badly dated. As reliable estimates of SCD incidence are important for improving risk stratification and prevention, future efforts are clearly needed to establish uniform definitions of SCA and SCD and then to prospectively and precisely capture cases of SCA and SCD in the overall U.S. population.",
"title": "Systematic Review of the Incidence of Sudden Cardiac Death in the United States"
},
{
"docid": "MED-2584",
"text": "In a 6-year prospective study, the authors examined the relation between diet and incident colon cancer among 32,051 non-Hispanic white cohort members of the Adventist Health Study (California, 1976-1982) who, at baseline, had no documented or reported history of cancer. The risk of colon cancer was determined from proportional hazards regression with adjustment for age and other covariates. The authors found a positive association with total meat intake (risk ratio (RR) for > or =1 time/week vs. no meat intake = 1.85, 95% confidence interval (CI) 1.19-2.87; p for trend = 0.01) and, among subjects who favored specific types of meat, positive associations with red meat intake (RR for > or =1 time/week vs. no red meat intake = 1.90, 95% CI 1.16-3.11; p for trend = 0.02) and white meat intake (RR for > or =1 time/week vs. no white meat intake = 3.29, 95% CI 1.60-6.75; p for trend = 0.006). An inverse association with legume intake (RR for >2 times/week vs. <1 time/week = 0.53, 95% CI 0.33-0.86; p for trend = 0.03) was observed. Among men, a positive association with body mass index was observed (relative to the RR for tertile III (>25.6 kg/m2) vs. tertile I (<22.5 kg/m2) = 2.63, 95% CI 1.12-6.13; p for trend = 0.05). A complex relation was identified whereby subjects exhibiting a high red meat intake, a low legume intake, and a high body mass experienced a more than threefold elevation in risk relative to all other patterns based on these variables. This pattern of putative risk factors would likely contribute to increases in both insulin resistance (high body mass, high red meat intake) and glycemic load (low legume intake), a synergism that, if causal, implicates hyperinsulinemic exposure in colon carcinogenesis. The overall findings from this cohort identify both red meat intake and white meat intake as important dietary risk factors for colon cancer and raise the possibility that the risk due to red meat intake reflects a more complex etiology.",
"title": "Dietary risk factors for colon cancer in a low-risk population."
},
{
"docid": "MED-1664",
"text": "The intervertebral disc is a cartilaginous structure that resembles articular cartilage in its biochemistry, but morphologically it is clearly different. It shows degenerative and ageing changes earlier than does any other connective tissue in the body. It is believed to be important clinically because there is an association of disc degeneration with back pain. Current treatments are predominantly conservative or, less commonly, surgical; in many cases there is no clear diagnosis and therapy is considered inadequate. New developments, such as genetic and biological approaches, may allow better diagnosis and treatments in the future.",
"title": "Degeneration of the intervertebral disc"
},
{
"docid": "MED-2180",
"text": "Objectives To compare the energy and macronutrient content of main meals created by television chefs with ready meals sold by supermarkets, and to compare both with nutritional guidelines published by the World Health Organization and UK Food Standards Agency. Design Cross sectional study. Setting Three supermarkets with the largest share of the grocery market in the United Kingdom, 2010. Samples 100 main meal recipes from five bestselling cookery books by UK television chefs and 100 own brand ready meals from the three leading UK supermarkets. Main outcome measures Number of meals for which the nutritional content complied with WHO recommendations, and the proportion of nutrients classified as red, amber, or green using the UK FSA’s “traffic light” system for labelling food. Results No recipe or ready meal fully complied with the WHO recommendations. The ready meals were more likely to comply with the recommended proportions of energy derived from carbohydrate (18% v 6%, P=0.01) and sugars (83% v 81%, P=0.05) and fibre density (56% v 14% P<0.01). The recipes were more likely to comply with the recommended sodium density (36% v 4%, P<0.01), although salt used for seasoning was not assessed. The distributions of traffic light colours under the FSA’s food labelling recommendations differed: the modal traffic light was red for the recipes (47%) and green for ready meals (42%). Overall, the recipes contained significantly more energy (2530 kJ v 2067 kJ), protein (37.5 g v 27.9 g), fat (27.1 g v 17.2 g), and saturated fat (9.2 g v 6.8 g; P<0.01 for all) and significantly less fibre (3.3 g v 6.5 g, P<0.01) per portion than the ready meals. Conclusions Neither recipes created by television chefs nor ready meals sold by three of the leading UK supermarkets complied with WHO recommendations. Recipes were less healthy than ready meals, containing significantly more energy, protein, fat, and saturated fat, and less fibre per portion than the ready meals.",
"title": "Christmas 2012: Research: Nutritional content of supermarket ready meals and recipes by television chefs in the United Kingdom: cross sectional study"
},
{
"docid": "MED-3278",
"text": "Lung cancer (LC) continues to represent a heavy burden for health care systems worldwide. Epidemiological studies predict that its role will increase in the near future. While patient prognosis is strongly associated with tumour stage and early detection of disease, no screening test exists so far. It has been suggested that electronic sensor devices, commonly referred to as ‘electronic noses’, may be applicable to identify cancer-specific volatile organic compounds in the breath of patients and therefore may represent promising screening technologies. However, three decades of research did not bring forward a clinically applicable device. Here, we propose a new research approach by involving specially trained sniffer dogs into research strategies by making use of their ability to identify LC in the breath sample of patients.",
"title": "Sniffer dogs as part of a bimodal bionic research approach to develop a lung cancer screening"
},
{
"docid": "MED-3109",
"text": "The aryl hydrocarbon receptor (AhR) is responsible for the toxic effects of environmental pollutants such as dioxin, but little is known about its normal physiological functions. Li et al. (2011) now show that specific dietary compounds present in cruciferous vegetables act through the AhR to promote intestinal immune function, revealing AhR as a critical link between diet and immunity. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "You AhR what you eat: linking diet and immunity."
},
{
"docid": "MED-2573",
"text": "A significant anticancer activity of the naturally occurring carbohydrate inositol hexaphosphate (IP(6)) has been reported against numerous cancer models. Since tumors require angiogenesis for growth and metastasis, we hypothesize that IP(6) reduces tumor growth by inhibiting angiogenesis. Because angiogenesis depends on the interaction between endothelial and tumor cells, we investigated the effect of IP(6) on both. IP(6) inhibited the proliferation and induced the differentiation of endothelial cells in vitro; the growth of bovine aortic endothelial cells (BAECs) evaluated by MTT proliferation assay was inhibited in a dose-dependent manner (IC(50) = 0.74 mM). The combination of IP(6) and vasostatin, a calreticulin fragment with anti-angiogenic activity, was synergistically superior in growth inhibition than either compound. IP(6) inhibited human umbilical vein endothelial cell (HUVEC) tube formation (in vitro capillary differentiation) on a reconstituted extracellular matrix, Matrigel, and disrupted pre-formed tubes. IP(6) significantly reduced basic fibroblast growth factor (bFGF)-induced vessel formation (P < 0.01) in vivo in Matrigel plug assay. Exposure of HepG2, a human hepatoma cell line, to IP(6) for 8 h, resulted in a dose-dependent decrease in the mRNA levels of vascular endothelial growth factor (VEGF), as assessed by RT-PCR. IP(6) treatment of HepG2 cells for 24 h also significantly reduced the VEGF protein levels in conditioned medium, in a concentration-dependent manner (P = 0.012). Thus, IP(6) has an inhibitory effect on induced angiogenesis.",
"title": "Anti-angiogenic activity of inositol hexaphosphate (IP6)."
},
{
"docid": "MED-1812",
"text": "Epidemiologic studies of diet and pancreas cancer are few, and include ecologic comparisons and a limited number of prospective and case-control studies. Foods and/or nutrients that have been suggested to be associated with increased risk of this cancer include total fat intake, eggs, animal protein, sugar, meat, coffee and butter. Consumption of raw fruits and vegetables has been consistently associated with decreased risk. Dietary habits and medical history variables were evaluated in a prospective study of fatal pancreas cancer among 34,000 California Seventh-day Adventists between 1976 and 1983. Forty deaths from pancreas cancer occurred during the follow-up period. Compared to all US whites, Adventists experienced decreased risk from pancreas cancer death (standardized mortality ratio [SMR] = 72 for men; 90 for women), which was not statistically significant. Although there was a suggestive relationship between increasing meat, egg, and coffee consumption and increased pancreatic cancer risk, these variables were not significantly related to risk after controlling for cigarette smoking. However, increasing consumption of vegetarian protein products, beans, lentils, and peas as well as dried fruit was associated with highly significant protective relationships to pancreas cancer risk. A prior history of diabetes was associated with increased risk of subsequent fatal pancreas cancer, as was a history of surgery for peptic or duodenal ulcer. A history of tonsillectomy was associated with a slight, nonsignificant protective relationship as was history of various allergic reactions. These findings suggest that the protective relationships associated with frequent consumption of vegetables and fruits high in protease-inhibitor content are more important than any increase in pancreas cancer risk attendant on frequent consumption of meat or other animal products. Furthermore, the previously reported positive associations between diabetes and abdominal surgery and pancreas cancer risk are supported in these data.",
"title": "Dietary habits and past medical history as related to fatal pancreas cancer risk among Adventists."
},
{
"docid": "MED-2122",
"text": "OBJECTIVE: To clarify the hormonal context of breast cancer etiology we used data from a large, population-based case-control study to investigate the relationship between breast cancer risk and a history of diabetes mellitus, disorders associated with estrogen stimulation (uterine fibroids, endometriosis, gallstones), and disorders associated with androgen stimulation (acne, hirsutism, and polycystic ovaries). METHODS: Breast cancer patients between 50 and 75 years old were identified from state-wide tumor registries in Wisconsin, Massachusetts, and New Hampshire; controls were randomly selected from drivers' license lists (age less than 65) or Medicare enrollment files (age 65-74). Information on reproductive history, medical history, and personal habits was obtained by telephone interview. A total of 5659 cases and 5928 controls were interviewed and provided suitable data. RESULTS: There was no overall association between breast cancer risk and reported history of diabetes mellitus, endometriosis, uterine fibroids, gallstones, or cholecystectomy. However, the disorders with androgenic associations all conferred an increased risk: the overall odds ratio (OR) for a history of acne was 1.4 (95% CI 1.0-1.9), that for hirsutism was 1.2 (95% CI 0.81-1.8), and that for polycystic ovaries 1.6 (95% CI 0.8-3.2). Diabetes mellitus diagnosed before age 35 conferred an odds ratio of 0.52 (95% 0.25-1.1), while diabetes diagnosed at a later age was associated with an increased risk (OR = 1.2, 95% CI 1.0-1.4). CONCLUSIONS: Androgen-related phenomena are likely to be important in the etiology of breast cancer.",
"title": "Metabolic disorders and breast cancer risk (United States)."
},
{
"docid": "MED-2988",
"text": "This review describes the present state of knowledge about phytic acid (phytate), which is often present in legume seeds. The antinutritional effects of phytic acid primarily relate to the strong chelating associated with its six reactive phosphate groups. Its ability to complex with proteins and particularly with minerals has been a subject of investigation from chemical and nutritional viewpoints. The hydrolysis of phytate into inositol and phosphates or phosphoric acid occurs as a result of phytase or nonenzymatic cleavage. Enzymes capable of hydrolysing phytates are widely distributed in micro-organisms, plants and animals. Phytases act in a stepwise manner to catalyse the hydrolysis of phytic acid. To reduce or eliminate the chelating ability of phytate, dephosphorylation of hexa- and penta-phosphate forms is essential since a high degree of phosphorylation is necessary to bind minerals. There are several methods of decreasing the inhibitory effect of phytic acid on mineral absorption (cooking, germination, fermentation, soaking, autolysis). Nevertheless, inositol hexaphosphate is receiving increased attention owing to its role in cancer prevention and/or therapy and its hypocholesterolaemic effect.",
"title": "The role of phytic acid in legumes: antinutrient or beneficial function?"
},
{
"docid": "MED-3108",
"text": "The external surfaces of the body, such as the skin and the gastrointestinal mucosal membrane, are an important line of defence preventing the invasion of microorganisms and their products. Mucosal immune cells, especially intraepithelial lymphocytes, are involved in maintaining the integrity of these epithelial barriers. They contribute towards the tolerance to commensal organisms, which occupy these same sites, and to the immune responses against harmful organisms and their products. The composition of the microbiota is influenced by immune cells as well as external environmental factors, especially the use of antibiotics and diet. There is an increasing appreciation that the microbiota affects systemic immune responses in addition to local immunity. Failure to control the occupancy by microorganisms may result in the disruption of the delicate homeostasis between beneficial and harmful microorganisms and contribute to inflammatory pathologies. This review will discuss some of our current understanding of the impact of immune cells and diet on the microbiota.",
"title": "Epithelial barrier biology: good fences make good neighbours"
},
{
"docid": "MED-2968",
"text": "There is increasing evidence implicating a dietary source of plasma lipid peroxides that become elevated in the postprandial state. This phenomenon may be a contributing factor to the correlation found between postprandial hyperlipidemia and increased risk of cardiovascular disease. Using a newly developed method for measuring lipid hydroperoxides directly in plasma, a pilot study was performed which revealed that lipid hydroperoxides are indeed elevated following a fatty meal. Lipid hydroperoxides increased within 2-4 h after the meal and returned to basal levels, corresponding to the usual postprandial hyperlipidemia. A marked suppression of postprandial hydroperoxides was found when a meal was consumed with wine, suggesting that these hydroperoxides can be formed and then absorbed during the digestive process.",
"title": "Postprandial plasma lipid hydroperoxides: a possible link between diet and atherosclerosis."
},
{
"docid": "MED-4450",
"text": "Little is known about the effects of diet after breast cancer diagnosis on survival. We prospectively examined the relation between post-diagnosis dietary factors and breast cancer and all-cause survival in women with a history of invasive breast cancer diagnosed between 1987 and 1999 (at ages 20–79 years). Diet after breast cancer diagnosis was measured using a 126-item food frequency questionnaire. Among 4,441 women without a history of breast cancer recurrence prior to completing the questionnaire, 137 subsequently died from breast cancer within 7 years of enrollment. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated for intake of macronutrients as well as selected micronutrients and food groups from Cox proportional hazards regression models. After adjustment for factors at diagnosis (age, state of residence, menopausal status, smoking, breast cancer stage, alcohol, history of hormone replacement therapy), interval between diagnosis and diet assessment, and at follow-up (energy intake, breast cancer treatment, body mass index, and physical activity), women in the highest compared to lowest quintile of intake of saturated fat and trans fat had a significantly higher risk of dying from any cause (HR = 1.41, 95% CI = 1.06 to 1.87, P-trend = 0.03) for saturated fat; (HR = 1.78, 95% CI = 1.35 to 2.32, P-trend = 0.01) for trans fat intake. Associations were similar, though did not achieve statistical significance, for breast cancer survival. This study suggests that lower intake of saturated and trans fat in the post-diagnosis diet is associated with improved survival after breast cancer diagnosis.",
"title": "Post-diagnosis dietary factors and survival after invasive breast cancer"
},
{
"docid": "MED-2970",
"text": "There is increasing evidence that the postprandial state is an important contributing factor to chronic disease. The role of fruit phenolic compounds to protect health and lower disease risk through their actions in mitigating fed-state metabolic and oxidative stressors is of interest and the topic of the present paper. Two main questions are posed: first, what is the role of plant foods, specifically fruits rich in complex and simple phenolic compounds in postprandial metabolic management; and second, does the evidence support consuming these fruits with meals as a practical strategy to preserve health and lower risk for disease? This review provides an overview of the postprandial literature, specifically on the effect of fruits and their inherent phenolic compounds in human subjects on postprandial lipaemia, glycaemia/insulinaemia and associated events, such as oxidative stress and inflammation. Among the identified well-controlled human trials using a postprandial paradigm, >50 % of the trials used wine or wine components and the remaining used various berries. Notwithstanding the need for more research, the collected data suggest that consuming phenolic-rich fruits increases the antioxidant capacity of the blood, and when they are consumed with high fat and carbohydrate 'pro-oxidant and pro-inflammatory' meals, they may counterbalance their negative effects. Given the content and availability of fat and carbohydrate in the Western diet, regular consumption of phenolic-rich foods, particularly in conjunction with meals, appears to be a prudent strategy to maintain oxidative balance and health.",
"title": "Postprandial metabolic events and fruit-derived phenolics: a review of the science."
},
{
"docid": "MED-2097",
"text": "The role of nutrition in onset, progression and treatment of periodontitis has not been thoroughly evaluated. In the present prospective clinical study, we investigated the influence of a nutritional intervention on changes in clinical, microbiological and immunological periodontal variables during a period of 12 months in patients with the metabolic syndrome and chronic periodontitis. Twenty female subjects with the metabolic syndrome and mild to moderate chronic periodontitis participated in a guided nutritional intervention programme. Examinations were assessed before, and at 2 weeks, 3, 6 and 12 months after intervention. Clinical measurements included probing depth, Löe and Silness gingival index and Quigley-Hein plaque index. In gingival crevicular fluid, periodontopathogens, levels of IL-1beta and IL-6 as well as the activity of granulocyte elastase were determined. In stimulated saliva, antioxidative and oxidative variables were measured. After 12 months the following significant changes could be observed: reduction of clinical probing depth (2.40 v. 2.20 mm; P < 0.001), reduction of gingival inflammation (gingival index 1.13 v. 0.9; P < 0.001), reduced concentrations of IL-1beta (4.63 v. 1.10 pg/ml per site; P < 0.001) as well as IL-6 (1.85 v. 0.34 pg/ml per site; P = 0.022) in gingival crevicular fluid. Bacterial counts in gingival crevicular fluid as well as oxidative and antioxidative variables in saliva showed no significant changes. Only salivary catalase showed a tendency to lower values. These findings indicate that in patients with the metabolic syndrome wholesome nutrition might reduce inflammatory variables of periodontal disease and promote periodontal health.",
"title": "Nutritional intervention in patients with periodontal disease: clinical, immunological and microbiological variables during 12 months."
},
{
"docid": "MED-4477",
"text": "Microwave-assisted extraction (MAE) and dispersive liquid-liquid microextraction (DLLME) coupled with gas chromatography-mass spectrometry (GC-MS) were evaluated for use in the extraction and preconcentration of volatile nitrosamines in meat products. Parameters affecting MAE, such as the extraction solvent used, and DLLME, including the nature and volume of the extracting and disperser solvents, extraction time, salt addition and centrifugation time, were optimized. In the MAE method, 0.25g of sample mass was extracted in 10mL NaOH (0.05M) in a closed-vessel system. For DLLME, 1.5mL of methanol (disperser solvent) containing 20μL of carbon tetrachloride (extraction solvent) was rapidly injected by syringe into 5mL of the sample extract solution (previously adjusted to pH 6), thereby forming a cloudy solution. Phase separation was performed by centrifugation, and a volume of 3μL of the sedimented phase was analyzed by GC-MS. The enrichment factors provided by DLLME varied from 220 to 342 for N-nitrosodiethylamine and N-nitrosopiperidine, respectively. The matrix effect was evaluated for different samples, and it was concluded that sample quantification can be carried out by aqueous calibration. Under the optimized conditions, detection limits ranged from 0.003 to 0.014ngmL(-1) for NPIP and NMEA, respectively (0.12-0.56ngg(-1) in the meat products). Copyright © 2011 Elsevier B.V. All rights reserved.",
"title": "Determination of volatile nitrosamines in meat products by microwave-assisted extraction and dispersive liquid-liquid microextraction coupled to ga..."
},
{
"docid": "MED-2293",
"text": "The CODEX Alimentarius definition of dietary fiber includes all nondigestible carbohydrate polymers with a degree of polymerization of 3 or more as dietary fiber with the proviso that they show health benefits. The global definition, if accepted by all authoritative bodies, offers a chance for international harmonization in research, food composition tables, and food labeling. Its nonacceptance highlights problems that may develop when definitions vary by region. The definition requires that the research community agrees upon physiological effects for which there is substantial scientific agreement, e.g., fibers’ effects on laxation and gut health, on attenuating blood lipids and blood glucose and insulin, and in promoting fermentation in the large bowel. The definition also necessitates the delineation of research protocols to prove the benefits of various isolated and synthesized fibers. These should emanate from evidence-based reviews that fairly weigh epidemiological data while considering that added fibers are not reflected in many food composition databases. They then should include well-controlled, randomized, control trials and utilize animal studies to determine mechanisms. Agreement on many study variables such as the type of subject and the type of baseline diet that best fits the question under investigation will also be needed. Finally, the definition establishes that all types of fiber can address the severe fiber consumption gap that exists throughout the world by recognizing that the combination of fiber-rich and -fortified foods increases fiber intake while allowing consumers to stay within allowed energy levels.",
"title": "Dietary Fiber Future Directions: Integrating New Definitions and Findings to Inform Nutrition Research and Communication"
},
{
"docid": "MED-2211",
"text": "BACKGROUND: China is increasingly facing the challenge of control of the growing burden of non-communicable diseases. We assessed the epidemiology of Alzheimer's disease and other forms of dementia in China between 1990, and 2010, to improve estimates of the burden of disease, analyse time trends, and inform health policy decisions relevant to China's rapidly ageing population. METHODS: In our systematic review we searched for reports of Alzheimer's disease or dementia in China, published in Chinese and English between 1990 and 2010. We searched China National Knowledge Infrastructure, Wanfang, and PubMed databases. Two investigators independently assessed case definitions of Alzheimer's disease and dementia: we excluded studies that did not use internationally accepted case definitions. We also excluded reviews and viewpoints, studies with no numerical estimates, and studies not done in mainland China. We used Poisson regression and UN demographic data to estimate the prevalence (in nine age groups), incidence, and standardised mortality ratio of dementia and its subtypes in China in 1990, 2000, and 2010. FINDINGS: Our search returned 12,642 reports, of which 89 met the inclusion criteria (75 assessed prevalence, 13 incidence, and nine mortality). In total, the included studies had 340,247 participants, in which 6357 cases of Alzheimer's disease were recorded. 254,367 people were assessed for other forms of dementia, of whom 3543 had vascular dementia, frontotemporal dementia, or Lewy body dementia. In 1990 the prevalence of all forms of dementia was 1·8% (95% CI 0·0-44·4) at 65-69 years, and 42·1% (0·0-88·9) at age 95-99 years. In 2010 prevalence was 2·6% (0·0-28·2) at age 65-69 years and 60·5% (39·7-81·3) at age 95-99 years. The number of people with dementia in China was 3·68 million (95% CI 2·22-5·14) in 1990, 5·62 million (4·42-6·82) in 2000, and 9·19 million (5·92-12·48) in 2010. In the same period, the number of people with Alzheimer's disease was 1·93 million (1·15-2·71) in 1990, 3·71 million (2·84-4·58) people in 2000, and 5·69 million (3·85-7·53) in 2010. The incidence of dementia was 9·87 cases per 1000 person-years, that of Alzheimer's disease was 6·25 cases per 1000 person-years, that of vascular dementia was 2·42 cases per 1000 person-years, and that of other rare forms of dementia was 0·46 cases per 1000 person-years. We retrieved mortality data for 1032 people with dementia and 20,157 healthy controls, who were followed up for 3-7 years. The median standardised mortality ratio was 1·94:1 (IQR 1·74-2·45). INTERPRETATION: Our analysis suggests that previous estimates of dementia burden, based on smaller datasets, might have underestimated the burden of dementia in China. The burden of dementia seems to be increasing faster than is generally assumed by the international health community. Rapid and effective government responses are needed to tackle dementia in low-income and middle-income countries. FUNDING: Nossal Institute of Global Health (University of Melbourne, Australia), the National 12th Five-Year Major Projects of China, National Health and Medical Research Council Australia-China Exchange Fellowship, Importation and Development of High-Calibre Talents Project of Beijing Municipal Institutions, and the Bill & Melinda Gates Foundation. Copyright © 2013 Elsevier Ltd. All rights reserved.",
"title": "Epidemiology of Alzheimer's disease and other forms of dementia in China, 1990-2010: a systematic review and analysis."
},
{
"docid": "MED-1208",
"text": "The growing macabre fascination with \"last meals\" offers a window into one's true consumption desires when one's value of the future is discounted close to zero. But in contrast to popular anecdotes and individual case studies, we created an empirical catalog of actual last meals - the final food requests of 247 individuals executed in the United States during a recent five-year period. Our content analyses reveal three key findings: (1) the average last meal is calorically rich (2756 calories) and proportionally averages 2.5 times the daily recommended servings of protein and fat, (2) the most frequent requests are also calorie dense: meat (83.9%), fried food (67.9%), desserts (66.3%), and soft drinks (60.0%), and (3) 39.9% requested branded foods or beverages. These findings are respectfully consistent with a model of environmentally contingent temporal discounting, and they are consistent with studies of how food is used to mediate feelings of stress and distress. Given that some people who are warned about the ill effects of obesity might counterintuitively engage in unhealthy overconsumption, the findings also suggest further study relating to the artificial use of mortality salience in campaigns against obesity. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Death row nutrition. Curious conclusions of last meals."
},
{
"docid": "MED-1506",
"text": "Intake of saturated fats and simple carbohydrates, two of the primary components of a modern Western diet, is linked with the development of obesity and Alzheimer's Disease. The present paper summarizes research showing that Western diet intake is associated with cognitive impairment, with a specific emphasis on learning and memory functions that are dependent on the integrity of the hippocampus. The paper then considers evidence that saturated fat and simple carbohydrate intake is correlated with neurobiological changes in the hippocampus that may be related to the ability of these dietary components to impair cognitive function. Finally, a model is described proposing that Western diet consumption contributes to the development of excessive food intake and obesity, in part, by interfering with a type of hippocampal-dependent memory inhibition that is critical in the ability of animals to refrain from responding to environmental cues associated with food, and ultimately from consuming energy intake in excess of that driven solely by caloric need.",
"title": "Western Diet Consumption and Cognitive Impairment: Links to Hippocampal Dysfunction and Obesity"
},
{
"docid": "MED-2089",
"text": "In this study, genotoxicity of two mouthwash products (chlorexidin, benzidamine-HCl) were investigated in the Drosophila Wing-Spot Test which makes use of the wing cell markers multiple wing hairs (mwh) and flare (flr) and detects both mitotic recombination and various types of mutational events. Induced mutations are detected as single mosaic spots on the wing blade of surviving adults that show either the multiple wing hairs or flare phenotype. Induced recombination leads to mwh and flr twin spots and also, to some extent, to mwh single spots. Recording of the frequency and the size of different spots is allowed for a quantitative determination of the mutagenic and recombinogenic effects. Trans-heterozygous third-instar larvae were treated at different concentrations of the mouthwash products. Chlorexidin exposure concentrations were 0.5, 1 and 2mg/ml. Benzidamine-HCl exposure concentrations were 0.38, 0.75 and 1.5mg/ml. In addition, the observed mutations were classified according to size and type of mutation per wing. Both chlorexidin and benzidamine-HCl were genotoxic in terms of total mutations per wing at the highest doses. Survival rates of flies used in the experiments were significantly lower than those of the control group, with both mouthwash products showing toxic effects on Drosophila melanogaster larvae. Copyright (c) 2010 Elsevier Ltd. All rights reserved.",
"title": "Genotoxicity of two mouthwash products in the Drosophila Wing-Spot Test."
},
{
"docid": "MED-2121",
"text": "The purpose of this paper is to highlight the endocrine signaling of Western diet, a fundamental environmental factor involved in the pathogenesis of epidemic acne. Western nutrition is characterized by high calorie uptake, high glycemic load, high fat and meat intake, as well as increased consumption of insulin- and IGF-1-level elevating dairy proteins. Metabolic signals of Western diet are sensed by the nutrient-sensitive kinase, mammalian target of rapamycin complex 1 (mTORC1), which integrates signals of cellular energy, growth factors (insulin, IGF-1) and protein-derived signals, predominantly leucine, provided in high amounts by milk proteins and meat. mTORC1 activates SREBP, the master transcription factor of lipogenesis. Leucine stimulates mTORC1-SREBP signaling and leucine is directly converted by sebocytes into fatty acids and sterols for sebaceous lipid synthesis. Over-activated mTORC1 increases androgen hormone secretion and most likely amplifies androgen-driven mTORC1 signaling of sebaceous follicles. Testosterone directly activates mTORC1. Future research should investigate the effects of isotretinoin on sebocyte mTORC1 activity. It is conceivable that isotretinoin may downregulate mTORC1 in sebocytes by upregulation of nuclear levels of FoxO1. The role of Western diet in acne can only be fully appreciated when all stimulatory inputs for maximal mTORC1 activation, i.e., glucose, insulin, IGF-1 and leucine, are adequately considered. Epidemic acne has to be recognized as an mTORC1-driven disease of civilization like obesity, type 2 diabetes, cancer and neurodegenerative diseases. These new insights into Western diet-mediated mTORC1-hyperactivity provide a rational basis for dietary intervention in acne by attenuating mTORC1 signaling by reducing (1) total energy intake, (2) hyperglycemic carbohydrates, (3) insulinotropic dairy proteins and (4) leucine-rich meat and dairy proteins. The necessary dietary changes are opposed to the evolution of industrialized food and fast food distribution of Westernized countries. An attenuation of mTORC1 signaling is only possible by increasing the consumption of vegetables and fruit, the major components of vegan or Paleolithic diets. The dermatologist bears a tremendous responsibility for his young acne patients who should be advised to modify their dietary habits in order to reduce activating stimuli of mTORC1, not only to improve acne but to prevent the harmful and expensive march to other mTORC1-related chronic diseases later in life.",
"title": "Dietary intervention in acne"
},
{
"docid": "MED-5190",
"text": "To investigate the association between dietary exposure to food mutagens and risk of pancreatic cancer, we conducted a hospital-based case-control study at the University of Texas M. D. Anderson Cancer Center during June 2002 to May 2006. Atotal of 626 cases and 530 noncancer controls were frequency matched for race, sex and age (±5 years). Dietary exposure information was collected via personal interview using a meat preparation questionnaire. A significantly greater portion of the cases than controls showed a preference to well-done pork, bacon, grilled chicken, and pan-fried chicken, but not to hamburger and steak. Cases had a higher daily intake of food mutagens and mutagenicity activity (revertants per gram of daily meat intake) than controls did. The daily intakes of 2-amino-3,4,8-trimethylimidazo[4,5—f]quinoxaline (DiMeIQx) and benzo(a)pyrene (BaP), as well as the mutagenic activity, were significant predictors for pancreatic cancer (P = 0.008, 0.031, and 0.029, respectively) with adjustment of other confounders. A significant trend of elevated cancer risk with increasing DiMeIQx intake was observed in quintile analysis (Ptrend= 0.024). Ahigher intake of dietary mutagens (those in the two top quintiles) was associated with a 2-fold increased risk of pancreatic cancer among those without a family history of cancer but not among those with a family history of cancer. Apossible synergistic effect of dietary mutagen exposure and smoking was observed among individuals with the highest level of exposure (top 10%) to PhIP and BaP, Pinteraction= 0.09 and 0.099, respectively. These data support the hypothesis that dietary mutagen exposure alone and in interaction with other factors contribute to the development of pancreatic cancer.",
"title": "Dietary Mutagen Exposure and Risk of Pancreatic Cancer"
},
{
"docid": "MED-4255",
"text": "The world's advanced countries have easy access to plentiful high-fat food; ironically, it is this rich diet that produces atherosclerosis. In the world's poorer nations, many people subsist on a primarily plant-based diet, which is far healthier, especially in terms of heart disease. To treat coronary heart disease, a century of scientific investigation has produced a device-driven, risk factor-oriented strategy. Nevertheless, many patients treated with this approach experience progressive disability and death. This strategy is a rear-guard defensive one. In contrast, compelling data from nutritional studies, population surveys, and interventional studies support the effectiveness of a plant-based diet and aggressive lipid lowering to arrest, prevent, and selectively reverse heart disease. In essence, this is an offensive strategy. The single biggest step toward adopting this strategy would be to have United States dietary guidelines support a plant-based diet. An expert committee purged of industrial and political influence is required to assure that science is the basis for dietary recommendations. (c)2001 CHF, Inc.",
"title": "Resolving the Coronary Artery Disease Epidemic Through Plant-Based Nutrition."
},
{
"docid": "MED-1582",
"text": "Background & Aims Increased intake of dietary fiber has been proposed to reduce risk of inflammatory bowel diseases (Crohn’s disease [CD], ulcerative colitis [UC]). However, few prospective studies have examined associations between long-term intake of dietary fiber and risk of incident CD or UC. Methods We collected and analyzed data from 170,776 women, followed over 26 y, who participated in the Nurses’ Health Study, followed for 3,317,425 person-y. Dietary information was prospectively ascertained via administration of a validated semi-quantitative food frequency questionnaire every 4 y. Self-reported CD and UC were confirmed through review of medical records. Cox proportional hazards models, adjusting for potential confounders, were used to calculate hazard ratios (HRs). Results We confirmed 269 incident cases of CD (incidence 8/100,000 person-y) and 338 cases of UC (incidence 10/100,000 person-y). Compared to the lowest quintile of energy-adjusted cumulative average intake of dietary fiber, intake of the highest quintile (median of 24.3 g/day) was associated with a 40% reduction in risk of CD (multivariate HR for CD, 0.59; 95% confidence interval [CI], 0.39–0.90). This apparent reduction appeared to be greatest for fiber derived from fruits; fiber from cereals, whole grains, or legumes did not modify risk. In contrast, neither total intake of dietary fiber (multivariate HR, 0.82; 95% CI 0.58–1.17) nor intake of fiber from specific sources appeared to be significantly associated with risk of UC. Conclusion Based on data from the Nurses’ Health Study, long-term intake of dietary fiber, particularly from fruit, is associated with lower risk of CD but not UC. Further studies are needed to determine the mechanisms that mediate this association.",
"title": "A Prospective Study of Long-term Intake of Dietary Fiber and Risk of Crohn’s Disease and Ulcerative Colitis"
},
{
"docid": "MED-2095",
"text": "During the last few years, there has been increasing interest in buccal epithelial cells for cytogenetic evaluation of different materials. In the present study, the use of these cells and peripheral lymphocytes for cytogenetic evaluation of chlorhexidine digluconate (CHX) with comet assay (single cell gel electrophoresis, or SCGE) is reported. This technique detects DNA strand breaks in individual cells in alkaline conditions. Thirteen volunteers were requested to rinse their mouths with 0.12% CHX solution for 18 days. Buccal epithelial cells and peripheral blood lymphocytes were obtained from all participants at baseline and the end of the experimental period. One hundred cells per subject were analysed for the DNA damage. A statistical increase was observed in the damaged buccal and blood cells after the CHX application. The mean grade of damage in buccal cells was statistically different from that in blood cells. Due to minimal absorption of chlorhexidine into the tissues and low concentrations of free chlorhexidine in the oral cavity, the DNA damage produced by chlorhexidine in lymphocytes was lower than in buccal epithelial cells. As chlorhexidine does not accumulate in the body, the frequencies of DNA damage could be transient. Detected DNA damage after CHX use might be the indication of an earlier effect, before DNA repair begins, and could be reversible.",
"title": "Monitoring of buccal epithelial cells by alkaline comet assay (single cell gel electrophoresis technique) in cytogenetic evaluation of chlorhexidine."
},
{
"docid": "MED-2585",
"text": "Inositol hexaphosphate (IP6) is a naturally occurring polyphosphorylated carbohydrate that is present in substantial amounts in almost all plant and mammalian cells. It was recently recognized to possess multiple biological functions. A striking anticancer effect of IP6 was demonstrated in different experimental models. Inositol is also a natural constituent possessing moderate anticancer activity. The most consistent and best anticancer results were obtained from the combination of IP6 plus inositol. In addition to reducing cell proliferation, IP6 increases differentiation of malignant cells, often resulting in a reversion to normal phenotype. Exogenously administered IP6 is rapidly taken into the cells and dephosphorylated to lower-phosphate inositol phosphates, which further interfere with signal transduction pathways and cell cycle arrest. Enhanced immunity and antioxidant properties can also contribute to tumor cell destruction. However, the molecular mechanisms underlying this anticancer action are not fully understood. Because it is abundantly present in regular diet, efficiently absorbed from the gastrointestinal tract, and safe, IP6 holds great promise in our strategies for the prevention and treatment of cancer. IP6 plus inositol enhances the anticancer effect of conventional chemotherapy, controls cancer metastases, and improves the quality of life, as shown in a pilot clinical trial. The data strongly argue for the use of IP6 plus inositol in our strategies for cancer prevention and treatment. However, the effectiveness and safety of IP6 plus inositol at therapeutic doses needs to be determined in phase I and phase II clinical trials in humans.",
"title": "Cancer inhibition by inositol hexaphosphate (IP6) and inositol: from laboratory to clinic."
},
{
"docid": "MED-4523",
"text": "Both lipophilic and hydrophilic antioxidant capacities were determined using the oxygen radical absorbance capacity (ORAC(FL)) assay with fluorescein as the fluorescent probe and 2,2'-azobis(2-amidinopropane) dihydrochloride as a peroxyl radical generator on over 100 different kinds of foods, including fruits, vegetables, nuts, dried fruits, spices, cereals, infant, and other foods. Most of the foods were collected from four different regions and during two different seasons in U.S. markets. Total phenolics of each sample were also measured using the Folin-Ciocalteu reagent. Hydrophilic ORAC(FL) values (H-ORAC(FL)) ranged from 0.87 to 2641 micromol of Trolox equivalents (TE)/g among all of the foods, whereas lipophilic ORAC(FL) values (L-ORAC(FL)) ranged from 0.07 to 1611 micromol of TE/g. Generally, L-ORAC(FL) values were <10% of the H-ORAC(FL) values except for a very few samples. Total antioxidant capacity was calculated by combining L-ORAC(FL) and H-ORAC(FL). Differences of ORAC(FL) values in fruits and vegetables from different seasons and regions were relatively large for some foods but could not be analyzed in detail because of the sampling scheme. Two different processing methods, cooking and peeling, were used on selected foods to evaluate the impact of processing on ORAC(FL). The data demonstrated that processing can have significant effects on ORAC(FL). Considering all of the foods analyzed, the relationship between TP and H-ORAC(FL) showed a very weak correlation. Total hydrophilic and lipophilic antioxidant capacity intakes were calculated to be 5558 and 166 micromol of TE/day, respectively, on the basis of data from the USDA Continuing Survey of Food Intakes by Individuals (1994-1996).",
"title": "Lipophilic and hydrophilic antioxidant capacities of common foods in the United States."
},
{
"docid": "MED-1187",
"text": "Background and aims: The causes of relapses of ulcerative colitis (UC) are unknown. Dietary factors have been implicated in the pathogenesis of UC. The aim of this study was to determine which dietary factors are associated with an increased risk of relapse of UC. Methods: A prospective cohort study was performed with UC patients in remission, recruited from two district general hospitals, who were followed for one year to determine the effect of habitual diet on relapse. Relapse was defined using a validated disease activity index. Nutrient intake was assessed using a food frequency questionnaire and categorised into tertiles. Adjusted odds ratios for relapse were determined using multivariate logistic regression, controlling for non-dietary factors. Results: A total of 191 patients were recruited and 96% completed the study. Fifty two per cent of patients relapsed. Consumption of meat (odds ratio (OR) 3.2 (95% confidence intervals (CI) 1.3–7.8)), particularly red and processed meat (OR 5.19 (95% CI 2.1–12.9)), protein (OR 3.00 (95% CI 1.25–7.19)), and alcohol (OR 2.71 (95% CI 1.1–6.67)) in the top tertile of intake increased the likelihood of relapse compared with the bottom tertile of intake. High sulphur (OR 2.76 (95% CI 1.19–6.4)) or sulphate (OR 2.6 (95% CI 1.08–6.3)) intakes were also associated with relapse and may offer an explanation for the observed increased likelihood of relapse. Conclusions: Potentially modifiable dietary factors, such as a high meat or alcoholic beverage intake, have been identified that are associated with an increased likelihood of relapse for UC patients. Further studies are needed to determine if it is the sulphur compounds within these foods that mediates the likelihood of relapse and if reducing their intake would reduce relapse frequency.",
"title": "Influence of dietary factors on the clinical course of ulcerative colitis: a prospective cohort study"
},
{
"docid": "MED-1951",
"text": "Late preterm (LP) birth (34 0/7 - 36 6/7 weeks' gestation) accounts for nearly three-fourths of all preterm births, making this population a sizeable public health concern. The immature fetal development associated with LP delivery increases the risk of mortality and short-term medical complications. Which combination of maternal, fetal, or neonatal risk factors may be most critical has only recently begun to be addressed, and whether LP birth's disruptive impact on brain development will exert adverse effects on neuropsychological functioning in childhood and adolescence has been understudied. Early data have shown a graded response, with LP children often functioning better than very preterm children but worse than term children, and with subtle intellectual and neuropsychological deficits in LP children compared with healthy children born at term gestational age. Further characterization of the neuropsychological profile is required and would be best accomplished through prospective longitudinal studies. Moreover, since moderate and LP births result in disparate medical and psychological outcomes, the common methodology of combining these participants into a single research cohort to assess risk and outcome should be reconsidered. The rapidly growing LP outcomes literature reinforces a critical principle: fetal development occurs along a dynamic maturational continuum from conception to birth, with each successive gestational day likely to improve overall outcome.",
"title": "Late preterm birth: a review of medical and neuropsychological childhood outcomes."
},
{
"docid": "MED-3226",
"text": "Context and Objective: Dietary intake of animal proteins is associated with an increase in urinary calcium and nephrolithiasis risk. We tested the hypothesis that the acid load imposed by dietary proteins causes this hypercalciuria. Design and Setting: In a short-term crossover metabolic study, an alkali salt was provided with a high-protein diet (HPD) to neutralize the acid load imparted by dietary proteins. Participants and Interventions: Eleven healthy volunteers were evaluated at the end of each of four phases while consuming metabolic diets with fixed calcium and sodium content. Phases 1 and 3 consisted of a control diet (CD). Phases 2 and 4 consisted of a eucaloric HPD (60 g/d animal proteins added to CD). Along with HPD in phases 2 and 4, subjects ingested 30 mEq twice daily of either potassium citrate (KCitrate, alkaline salt) or potassium chloride (KCl, control neutral salt). Results: KCitrate completely neutralized the acid load imparted by HPD (based on changes in urine pH and net acid excretion) and increased urinary citrate. Urinary calcium increased during both HPD phases compared with CD but was not significantly different between the HPD + KCl and HPD + KCitrate phases (182 ± 85 vs. 170 ± 85 mg/d; P = 0.28). Increased urinary saturation with respect to calcium oxalate and uric acid with HPD was abrogated by KCitrate. Conclusions: This study suggests that, at least in the short-term, mechanism(s) other than acid load account for hypercalciuria induced by HPD. The beneficial effect of KCitrate on nephrolithiasis risk with HPD is through correction of declines in urine pH and citrate.",
"title": "Hypercalciuria Associated with High Dietary Protein Intake Is Not Due to Acid Load"
},
{
"docid": "MED-1660",
"text": "OBJECTIVES: Atherosclerosis of arteries supplying the lumbar region has been suggested as a mechanism leading to intervertebral disc degeneration and sciatica. The study described here examined whether serum lipid levels or pharmacologically treated hyperlipidemia were associated with sciatica. METHODS: A nationally representative sample (n=8028) of Finns aged 30 years or over was interviewed and examined. Sciatica was assessed by a physician according to preset criteria. Information for the present purpose was available for 74.8% of the sample. RESULTS: The prevalence of sciatica was 3.3% for men and 2.2% for women. In men without hyperlipidemia treatment, sciatica was associated with total cholesterol (high vs. low tertile: OR 2.28, 95% CI 1.14-4.55), LDL cholesterol (2.12; 1.11-4.05), and triglycerides (1.92; 1.04-3.55), adjusted for age, BMI, exercise, smoking, heavy physical work, and education. HDL was not associated with sciatica. For men in the highest tertile of both total cholesterol and triglycerides, the OR of sciatica was 3.89 (1.68-8.99) in comparison to men with cholesterol in the lowest tertile and triglycerides in the lowest or the middle tertile. In similar analyses among women no associations were seen. Pharmacologically treated hyperlipidemia was associated with sciatica in women (2.02; 1.01-4.04), but not in men (1.71; 0.83-3.55). CONCLUSIONS: Independent of BMI and other possible confounders, clinically assessed sciatica in men was associated with levels of atherogenic serum lipids. Pharmacologically treated hyperlipidemia was associated with sciatica in women. The findings are in accordance with the atherosclerosis-sciatica hypothesis.",
"title": "Serum lipids in relation to sciatica among Finns."
},
{
"docid": "MED-2506",
"text": "Long-term caloric restriction (CR) is a robust means of reducing age-related diseases and extending life span in multiple species, but the effects in humans are unknown. The low caloric intake, long life expectancy, and the high prevalence of centenarians in Okinawa have been used as an argument to support the CR hypothesis in humans. However, no long-term, epidemiologic analysis has been conducted on traditional dietary patterns, energy balance, and potential CR phenotypes for the specific cohort of Okinawans who are purported to have had a calorically restricted diet. Nor has this cohort's subsequent mortality experience been rigorously studied. Therefore, we investigated six decades of archived population data on the elderly cohort of Okinawans (aged 65-plus) for evidence of CR. Analyses included traditional diet composition, energy intake, energy expenditure, anthropometry, plasma DHEA, mortality from age-related diseases, and current survival patterns. Findings include low caloric intake and negative energy balance at younger ages, little weight gain with age, life-long low BMI, relatively high plasma DHEA levels at older ages, low risk for mortality from age-related diseases, and survival patterns consistent with extended mean and maximum life span. This study lends epidemiologic support for phenotypic benefits of CR in humans and is consistent with the well-known literature on animals with regard to CR phenotypes and healthy aging.",
"title": "Caloric restriction, the traditional Okinawan diet, and healthy aging: the diet of the world's longest-lived people and its potential impact on mor..."
},
{
"docid": "MED-4886",
"text": "OBJECTIVES: Previous research has demonstrated that patients with prostate cancer participating in the Prostate Cancer Lifestyle Trial had a reduction in prostate-specific antigen (PSA) levels, inhibition of LNCaP cell growth, and fewer prostate cancer-related clinical events at the end of 1 year compared with controls. The aim of this study was to examine the clinical events in this trial during a 2-year period. METHODS: The Prostate Cancer Lifestyle Trial was a 1-year randomized controlled clinical trial of 93 patients with early-stage prostate cancer (Gleason score <7, PSA 4-10 ng/mL) undergoing active surveillance. The patients in the experimental arm were encouraged to adopt a low-fat, plant-based diet, to exercise and practice stress management, and to attend group support sessions. The control patients received the usual care. RESULTS: By 2 years of follow-up, 13 of 49 (27%) control patients and 2 of 43 (5%) experimental patients had undergone conventional prostate cancer treatment (radical prostatectomy, radiotherapy, or androgen deprivation, P < .05). No differences were found between the groups in other clinical events (eg, cardiac), and no deaths occurred. Three of the treated control patients but none of the treated experimental patients had a PSA level of >or=10 ng/mL, and 1 treated control patient but no treated experimental patients had a PSA velocity of >2 ng/mL/y before treatment. No significant differences were found between the untreated experimental and untreated control patients in PSA change or velocity at the end of 2 years. CONCLUSIONS: Patients with early-stage prostate cancer choosing active surveillance might be able to avoid or delay conventional treatment for at least 2 years by making changes in their diet and lifestyle.",
"title": "Clinical events in prostate cancer lifestyle trial: results from two years of follow-up."
},
{
"docid": "MED-3700",
"text": "Background An increased risk of breast cancer is associated with alcohol consumption; however, it is controversial whether red wine increases this risk. Aromatase inhibitors (AIs) prevent the conversion of androgens to estrogen and occur naturally in grapes, grape juice, and red, but not white wine. We tested whether red wine is a nutritional AI in premenopausal women. Methods In a cross-over design, 36 women (mean age [SD], 36 [8] years) were assigned to 8 ounces (237 mL) of red wine daily then white wine for 1 month each, or the reverse. Blood was collected twice during the menstrual cycle for measurement of estradiol (E2), estrone (E1), androstenedione (A), total and free testosterone (T), sex hormone binding globulin (SHBG), luteinizing hormone (LH), and follicle stimulating hormone (FSH). Results Red wine demonstrated higher free T vs. white wine (mean difference 0.64 pg/mL [0.2 SE], p=0.009) and lower SHBG (mean difference −5.0 nmol/L [1.9 SE], p=0.007). E2 levels were lower in red vs. white wine but not statistically significant. LH was significantly higher in red vs. white wine (mean difference 2.3 mIU/mL [1.3 SE], p=0.027); however, FSH was not. Conclusion Red wine is associated with significantly higher free T and lower SHBG levels, as well as a significant higher LH level vs. white wine in healthy premenopausal women. These data suggest that red wine is a nutritional AI and may explain the observation that red wine does not appear to increase breast cancer risk.",
"title": "Red Versus White Wine as a Nutritional Aromatase Inhibitor in Premenopausal Women: A Pilot Study"
},
{
"docid": "MED-3271",
"text": "Most metastatic tumors, such as those originating in the prostate, lung, and gastrointestinal tract, respond poorly to conventional chemotherapy. Novel treatment strategies for advanced cancer are therefore desperately needed. Dietary restriction of the essential amino acid methionine offers promise as such a strategy, either alone or in combination with chemotherapy or other treatments. Numerous in vitro and animal studies demonstrate the effectiveness of dietary methionine restriction in inhibiting growth and eventually causing death of cancer cells. In contrast, normal host tissues are relatively resistant to methionine restriction. These preclinical observations led to a phase I clinical trial of dietary methionine restriction for adults with advanced cancer. Preliminary findings from this trial indicate that dietary methionine restriction is safe and feasible for the treatment of patients with advanced cancer. In addition, the trial has yielded some preliminary evidence of antitumor activity. One patient with hormone-independent prostate cancer experienced a 25% reduction in serum prostate-specific antigen (PSA) after 12 weeks on the diet, and a second patient with renal cell cancer experienced an objective radiographic response. The possibility that methionine restriction may act synergistically with other cancer treatments such as chemotherapy is being explored. Findings to date support further investigation of dietary methionine restriction as a novel treatment strategy for advanced cancer.",
"title": "Can dietary methionine restriction increase the effectiveness of chemotherapy in treatment of advanced cancer?"
},
{
"docid": "MED-3230",
"text": "OBJECTIVE: Diet affects urine pH and acid-base balance. Both excess acid/alkaline ash (EAA) and estimated net acid excretion (NAE) calculations have been used to estimate the effects of diet on urine pH. This study's goal was to determine if free-living vegans, lacto-ovo vegetarians, and omnivores have increasingly acidic urine, and to assess the ability of EAA and estimated NAE calculations to predict urine pH. DESIGN: This study used a cross-sectional design. SETTING AND PARTICIPANTS: This study assessed urine samples of 10 vegan, 16 lacto-ovo vegetarian, and 16 healthy omnivorous women in the Boston metropolitan area. Six 3-day food records from each dietary group were analyzed for EAA content and estimated NAE, and correlations with measured urine pH were calculated. RESULTS: The mean (+/- SD) urine pH was 6.15 +/- 0.40 for vegans, 5.90 +/- 0.36 for lacto-ovo vegetarians, and 5.74 +/- 0.21 for omnivores (analysis of variance, P = .013). Calculated EAA values were not significantly different among the three groups, whereas mean estimated NAE values were significantly different: 17.3 +/- 14.5 mEq/day for vegans, 31.3 +/- 8.5 mEq/day for lacto-ovo vegetarians, and 42.6 +/- 13.2 mEq/day for omnivores (analysis of variance, P = .01). The average deattenuated correlation between urine pH and EAA was 0.333; this value was -0.768 for estimated NAE and urine pH, with a regression equation of pH = 6.33 - 0.014 NAE (P = .02, r = -0.54). CONCLUSIONS: Habitual diet and estimated NAE calculations indicate the probable ranking of urine pH by dietary groups, and may be used to determine the likely acid-base status of an individual; EAA calculations were not predictive of urine pH.",
"title": "Estimated net acid excretion inversely correlates with urine pH in vegans, lacto-ovo vegetarians, and omnivores."
},
{
"docid": "MED-2290",
"text": "Background Differences in nutrient profiles between vegetarian and non vegetarian dietary patterns reflect nutritional differences that may contribute to the development of disease. Objective To compare nutrient intakes between dietary patterns characterized by consumption or exclusion of meat and dairy products. Design Cross-sectional study of 71751 subjects (mean age 59 years) from the Adventist-Health-Study-2. Data was collected between 2002 and 2007. Participants completed a 204-item validated semi-quantitative food frequency questionnaire. Dietary patterns compared were: non vegetarian, semi vegetarian, pesco vegetarian, lacto-ovo vegetarian and strict vegetarian. ANCOVA was used to analyze differences in nutrient intakes by dietary patterns and were adjusted for age, and sex and race. BMI and other relevant demographic data were reported and compared by dietary pattern using chi-square tests and ANOVA. Results Many nutrient intakes varied significantly between dietary patterns. Non vegetarians had the lowest intakes of plant proteins, fiber, β-Carotene, and Mg than those following vegetarian dietary patterns and the highest intakes of saturated, trans, arachidonic, and docosahexaenoic fatty acids. The lower tails of some nutrient distributions in strict vegetarians suggested inadequate intakes by a portion of the subjects. Energy intake was similar among dietary patterns at close to 2000 kcal/d with the exception of semi vegetarians that had an intake of 1713 kcal/d. Mean BMI was highest in non-vegetarians (mean; standard deviation [SD]) (28.7; [6.4]) and lowest in strict vegetarians (24.0; [4.8]). Conclusions Nutrient profiles varied markedly between dietary patterns that were defined by meat and dairy intakes. These differences can be of interest in the etiology of obesity and chronic diseases.",
"title": "Nutrient Profiles of Vegetarian and Non Vegetarian Dietary Patterns"
},
{
"docid": "MED-1497",
"text": "Traumatic brain injury (TBI) constitutes a major global health and socio-economic problem with neurobehavioral sequelae contributing to long-term disability. It causes brain swelling, axonal injury and hypoxia, disrupts blood brain barrier function and increases inflammatory responses, oxidative stress, neurodegeneration and leads to cognitive impairment. Epidemiological studies show that 30% of patients, who die of TBI, have Aβ plaques which are pathological features of Alzheimer's disease (AD). Thus TBI acts as an important epigenetic risk factor for AD. This review focuses on AD related genes which are expressed during TBI and its relevance to progression of the disease. Such understanding will help to diagnose the risk of TBI patients to develop AD and design therapeutic interventions. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Traumatic brain injury: a risk factor for Alzheimer's disease."
},
{
"docid": "MED-2489",
"text": "A historical view on how our agricultural systems evolved and how they are contributing to obesity and disease.",
"title": "Agricultural policies, food and public health"
},
{
"docid": "MED-2582",
"text": "Nonstarch polysaccharide (NSP) intake was measured in representative samples of 30 men aged 50-59 in 2 urban and 2 rural Scandinavian populations that exhibited a 3-4 fold difference in incidence of large bowel cancer. Intake was measured by chemical analysis of complete duplicate portions of all food eaten over one day by each individual. NSP intakes showed a rural-urban gradient, with 18.4 +/- 7.8 g/day in rural Finland and 18.0 +/- 6.4 g/day in rural Denmark versus 14.5 +/- 5.4 g/day in urban Finland and 13.2 +/- 4.8 g/day in urban Denmark. NSP intakes were also calculated (using food tables) from weighed food records kept over 4 days, one of which was the day on which the duplicate collection was made. Intakes were 2-2.5 g/day higher with this method than with direct chemical analysis, mainly because published tables of values have become outdated and inaccurate as a result of improved methods for measuring NSP in food. Individual variation from day to day in NSP intake was considerable. Average NSP intake and intake of some of its component sugars were inversely related to colon cancer incidence in this geographical comparison. To show a relationship at the individual level between diet and cancer risk in a prospective study would require detailed and accurate methods for the assessment of NSP consumption.",
"title": "Nonstarch polysaccharide consumption in four Scandinavian populations."
},
{
"docid": "MED-2216",
"text": "BACKGROUND: Alzheimer's disease (AD) rates in Japan and developing countries have risen rapidly in recent years. Researchers have associated factors such as the Western diet, obesity, alcohol consumption, and smoking with risk of AD. OBJECTIVE: This paper evaluates whether the dietary transition might explain the rising trend of AD prevalence in Japan and in developing countries, evaluating other factors when possible. METHODS: This study used two approaches to see whether dietary or other changes could explain AD trends in Japan and developing countries. One approach involved comparing trends of AD in Japan with changes in national dietary supply factors, alcohol consumption, and lung cancer mortality rates from zero to 25 years before the prevalence data. The second compared AD prevalence values for eight developing countries with dietary supply factors from zero to 25 years before the prevalence data. RESULTS: For Japan, alcohol consumption, animal product, meat and rice supply, and lung cancer rates correlated highly with AD prevalence data, with the strongest correlation for a lag of 15-25 years. In the eight-country study, total energy and animal fat correlated highly with AD prevalence data, with a lag of 15-20 years. Mechanisms to explain the findings include increased obesity for the eight countries, and increases in cholesterol, saturated fat, and iron from increases in animal products and meat supply for Japan. CONCLUSION: Evidently AD rates will continue rising in non-Western countries for some time unless we address major risk factors involving diet, obesity, and smoking.",
"title": "Trends in diet and Alzheimer's disease during the nutrition transition in Japan and developing countries."
},
{
"docid": "MED-4474",
"text": "The effect of dietary components on the levels of nitrosoproline ( NPRO ) excreted over a 24 h period in the urine was examined in volunteers ingesting known amounts of various food products. The ingestion of nitrite-preserved meats (85-170 g per meal), including canned, rolled or Yunnan ham, cured pork, luncheon meat, and various Chinese and European-style sausages, led to urinary NPRO excretion levels ranging from 2.5 to 78.5 micrograms/24 h, whereas the consumption of non-preserved meat and fish products, including chicken, herring, salmon, shrimp, ground beef (hamburger), pork chops and beef liver, led to relatively low NPRO excretion levels, ranging from 0.0 to 0.8 micrograms/24 h. The urinary NPRO levels of 22 vegetarians and 14 lacto-vegetarians averaged 0.8 and 1.4 micrograms/24 h, respectively. A change from a nitrite-preserved meat diet to a vegetarian diet was accompanied by an approximately six-fold reduction in urinary NPRO levels; however, these remained above control levels for at least 3 days following the dietary change. The relatively high NPRO levels following the ingestion of nitrite-preserved meats could not be reduced by nitrite-trapping chemicals, including ascorbic acid, ferulic acid, caffeic acid, or phenolic-containing mixtures such as coffee and tea, which were effective in suppressing endogenous NPRO formation following the intake of nitrate and proline. The high urinary NPRO levels after ingestion of preserved meat products appear to be due to the consumption of preformed NPRO . An understanding of the relative contribution of preformed and endogenously formed nitrosamines appears to be essential when designing dietary intervention programmes.",
"title": "The effect of dietary factors on nitrosoproline levels in human urine."
},
{
"docid": "MED-2372",
"text": "BACKGROUND: Because of egg cholesterol content, reduction in egg consumption is generally recommended to reduce risk of cardiovascular disease. Recently, however, evidence has been accumulating to suggest that dietary cholesterol is less relevant to cardiovascular risk than dietary saturated fat. This randomized controlled crossover trial was conducted to determine the effects of egg ingestion on endothelial function, a reliable index of cardiovascular risk. METHODS: Forty-nine healthy adults (mean age 56 years, 40% females) underwent a baseline brachial artery reactivity study (BARS), and were assigned to two eggs or oats daily for 6 weeks in random sequence with a 4-week washout. A BARS was done at the end of each treatment phase, measuring flow-mediated vasodilation (FMD) in the brachial artery using a high-frequency ultrasound. RESULTS: FMD was stable in both egg and oat groups, and between-treatment differences were not significant (egg -0.96%, oatmeal -0.79%; p value >0.05). Six weeks of egg ingestion had no effect on total cholesterol (baseline: 203.8 mg/dl; post-treatment: 205.3) or LDL (baseline: 124.8 mg/dl; post-treatment: 129.1). In contrast, 6 weeks of oats lowered total cholesterol (to 194 mg/dl; p = 0.0017) and LDL (to 116.6 mg/dl; p = 0.012). There were no differences in body mass index (BMI), triglyceride, HDL or SBP levels between egg and oat treatment assignments. CONCLUSION: Short-term egg consumption does not adversely affect endothelial function in healthy adults, supporting the view that dietary cholesterol may be less detrimental to cardiovascular health than previously thought.",
"title": "Egg consumption and endothelial function: a randomized controlled crossover trial."
},
{
"docid": "MED-2568",
"text": "Inositol hexaphosphate (InsP6 or IP6) is ubiquitous. At 10 microM to 1 mM concentrations, IP6 and its lower phosphorylated forms (IP(1-5)) as well as inositol (Ins) are contained in most mammalian cells, wherein they are important in regulating vital cellular functions such as signal transduction, cell proliferation and differentiation. A striking anti-cancer action of IP6 has been demonstrated both in vivo and in vitro, which is based on the hypotheses that exogenously administered IP6 may be internalized, dephosphorylated to IP(1-5), and inhibit cell growth. There is additional evidence that Ins alone may further enhance the anti-cancer effect of IP6. Besides decreasing cellular proliferation, IP6 also causes differentiation of malignant cells often resulting in a reversion to normal phenotype. These data strongly point towards the involvement of signal transduction pathways, cell cycle regulatory genes, differentiation genes, oncogenes and perhaps, tumor suppressor genes in bringing about the observed anti-neoplastic action of IP6.",
"title": "IP6: a novel anti-cancer agent."
},
{
"docid": "MED-2291",
"text": "PURPOSE: This review focuses on the health benefits of viscous versus nonviscous soluble fibers, why symptoms can occur with increased fiber consumption, and how to avoid symptoms to improve adherence with a high-fiber diet. DATA SOURCES: Review of scientific literature as well as evidence-based guidelines and resources. CONCLUSIONS: While it is generally known that \"fiber is good for you,\" it is less well known that specific health benefits are associated with specific fiber characteristics. Many of the health benefits of fiber can be directly correlated with the viscosity of soluble fibers when hydrated (i.e., gel-forming). A reduction in viscosity of a given fiber will attenuate these health benefits, and a nonviscous fiber does not exhibit these health benefits. IMPLICATIONS FOR PRACTICE: Increasing the viscosity of chyme with a viscous soluble fiber has been shown clinically to lower cholesterol for cardiovascular health, improve glycemic control in type 2 diabetes, normalize stool form in both constipation (softens hard stool) and diarrhea (firms loose/liquid stool), and improve the objective clinical measures of metabolic syndrome (glycemic control, lipoprotein profile, body mass index/weight loss, and blood pressure). ©2012 The Author(s) Journal compilation ©2012 American Academy of Nurse Practitioners.",
"title": "Viscous versus nonviscous soluble fiber supplements: mechanisms and evidence for fiber-specific health benefits."
},
{
"docid": "MED-4337",
"text": "The ingestion of fatty meals is associated with a transient, low-grade systemic inflammatory response in human subjects, involving the activation of circulating monocytes and the secretion of pro-inflammatory cytokines. However, it is not yet clear how different foodstuffs may promote inflammatory signalling. In a screen of forty filter-sterilised soluble extracts from common foodstuffs, seven were found to induce the secretion of TNF-α and IL-6 from human monocytes in vitro. To investigate what may differentiate inflammatory from non-inflammatory food extracts, stimulants of Toll-like receptor (TLR) 2 and TLR4 were quantified using human embryonic kidney-293 cells transfected with each TLR, and calibrated with defined bacterial lipopeptide (BLP) and lipopolysaccharide (LPS) standards. These assays revealed that while most foods contained undetectable levels of TLR2 or TLR4 stimulants, all TNF-α-inducing foods contained stimulants of either TLR2 (up to 1100 ng BLP-equivalent/g) or TLR4 (up to 2700 ng LPS-equivalent/g) in both the soluble and insoluble fractions. TLR stimulants were present mainly in meat products and processed foods, but were minimal or undetectable in fresh fruit and vegetables. The capacity of food extracts to induce TNF-α secretion in monocytes correlated with the content of both TLR2 (r 0·837) and TLR4 stimulants (r 0·748), and was completely abolished by specific inhibition of TLR2 and TLR4. LPS and BLP were found to be highly resistant to typical cooking times and temperatures, low pH and protease treatment. In conclusion, apparently unspoiled foodstuffs can contain large quantities of stimulants of TLR2 and TLR4, both of which may regulate their capacity to stimulate inflammatory signalling.",
"title": "The capacity of foodstuffs to induce innate immune activation of human monocytes in vitro is dependent on food content of stimulants of Toll-like r..."
},
{
"docid": "MED-1871",
"text": "In order to compare the antihypertensive effectiveness and tolerability of a standardized extract from Hibiscus sabdariffa with captopril, a controlled and randomized clinical trial was done. Patients from 30 to 80 years old with diagnosed hypertension and without antihypertensive treatment for at least 1 month before were included. The experimental procedure consisted of the administration of an infusion prepared with 10 g of dry calyx from H. sabdariffa on 0.51 water (9.6 mg anthocyanins content), daily before breakfast, or captopril 25 mg twice a day, for 4 weeks. The outcome variables were tolerability, therapeutic effectiveness (diastolic reduction > or = 10 mm Hg) and, in the experimental group, urinary electrolytes modification. Ninety subjects were included, 15 withdrew from the study due to non-medical reasons; so, the analysis included 39 and 36 patients from the experimental and control group, respectively. The results showed that H. sabdariffa was able to decrease the systolic blood pressure (BP) from 139.05 to 123.73mm Hg (ANOVA p < 0.03) and the diastolic BP from 90.81 to 79.52mm Hg (ANOVA p < 0.06). At the end of the study, there were no significant differences between the BP detected in both treatment groups (ANOVA p > 0.25). The rates of therapeutic effectiveness were 0.7895 and 0.8438 with H. sabdariffa and captopril, respectively (chi2, p > 0.560), whilst the tolerability was 100% for both treatments. A natriuretic effect was observed with the experimental treatment. The obtained data confirm that the H. sabdariffa extract, standardized on 9.6mg of total anthocyanins, and captopril 50 mg/day, did not show significant differences relative to hypotensive effect, antihypertensive effectiveness, and tolerability.",
"title": "Effectiveness and tolerability of a standardized extract from Hibiscus sabdariffa in patients with mild to moderate hypertension: a controlled and ..."
},
{
"docid": "MED-1190",
"text": "The serum concentration of high-density lipoprotein cholesterol and the proportion it constitutes of total serum cholesterol are high in children and low in sufferers from coronary heart disease (CHD). Studies in elderly black Africans in Western Transvaal showed them to be free of CHD. HDL concentrations measured at birth and in groups of 10- to 12-year-olds, 16- to 18-year olds, and 60- to 69-year-olds showed mean values of 0.96, 1.71, 1.58, and 1.94 mmol/l (36, 66, 61, and 65 mg/100 ml) respectively; these concentrations constitued about 56%, 54%, and 45%, and 47%, of total cholesterol. Values thus did not fall from youth to age as they did in whites. Rural South African blacks live on a diet high in fibre and low in animal protein and fat; children are active; and adults remain active even when old. These high values of HDL may well be representative for a population that is active, used to a frugal traditional diet, and free from CHD.",
"title": "High high-density-lipoprotein cholesterol in African children and adults in a population free of coronary heart diseae."
},
{
"docid": "MED-1207",
"text": "The response to arterial wall injury is an inflammatory process, which over time becomes integral to the development of atherosclerosis and subsequent plaque instability. However, the underlying injurious agent, critical to this process, has not received much attention. In this review, a model of plaque rupture is hypothesized with two stages of inflammatory activity. In stage I (cholesterol crystal-induced cell injury and apoptosis), intracellular cholesterol crystals induce foam cell apoptosis, setting up a vicious cycle by signaling more macrophages, resulting in accumulation of extra cellular lipids. This local inflammation eventually leads to the formation of a semi-liquid, lipid-rich necrotic core of a vulnerable plaque. In stage II (cholesterol crystal-induced arterial wall injury), the saturated lipid core is now primed for crystallization, which can manifest as a clinical syndrome with a systemic inflammation response. Cholesterol crystallization is the trigger that causes core expansion, leading to intimal injury. We recently demonstrated that when cholesterol crystallizes from a liquid to a solid state, it undergoes volume expansion, which can tear the plaque cap. This observation of cholesterol crystals perforating the cap and intimal surface was made in the plaques of patients who died with acute coronary syndrome. We have also demonstrated that several agents (ie, statins, aspirin, and ethanol) can dissolve cholesterol crystals and may be exerting their immediate benefits by this direct mechanism. Also, because recent studies have demonstrated that high-sensitivity C-reactive protein may be a reliable marker in selecting patients for statin therapy, it could reflect the presence of intimal injury by cholesterol crystals. This was demonstrated in an atherosclerotic rabbit model. Therefore, we propose that cholesterol crystallization could help explain in part both local and systemic inflammation associated with atherosclerosis. Copyright © 2010 National Lipid Association. Published by Elsevier Inc. All rights reserved.",
"title": "Cholesterol crystals piercing the arterial plaque and intima trigger local and systemic inflammation."
},
{
"docid": "MED-2455",
"text": "BACKGROUND: It has been postulated that dietary antioxidants may influence the expression of allergic diseases and asthma. To test this hypothesis a case-control study was performed, nested in a cross sectional study of a random sample of adults, to investigate the relationship between allergic disease and dietary antioxidants. METHODS: The study was performed in rural general practices in Grampian, Scotland. A validated dietary questionnaire was used to measure food intake of cases, defined, firstly, as people with seasonal allergic-type symptoms and, secondly, those with bronchial hyperreactivity confirmed by methacholine challenge, and of controls without allergic symptoms or bronchial reactivity. RESULTS: Cases with seasonal symptoms did not differ from controls except with respect to the presence of atopy and an increased risk of symptoms associated with the lowest intake of zinc. The lowest intakes of vitamin C and manganese were associated with more than fivefold increased risks of bronchial reactivity. Decreasing intakes of magnesium were also significantly associated with an increased risk of hyperreactivity. CONCLUSIONS: This study provides evidence that diet may have a modulatory effect on bronchial reactivity, and is consistent with the hypothesis that the observed reduction in antioxidant intake in the British diet over the last 25 years has been a factor in the increase in the prevalence of asthma over this period.",
"title": "Bronchial reactivity and dietary antioxidants"
},
{
"docid": "MED-1408",
"text": "OBJECTIVE: This meta-analysis aims to quantitatively synthesize all studies that examine the association between adherence to a Mediterranean diet and risk of stroke, depression, cognitive impairment, and Parkinson disease. METHODS: Potentially eligible publications were those providing effect estimates of relative risk (RR) for the association between Mediterranean diet and the aforementioned outcomes. Studies were sought in PubMed up to October 31, 2012. Maximally adjusted effect estimates were extracted; separate analyses were performed for high and moderate adherence. RESULTS: Twenty-two eligible studies were included (11 covered stroke, 9 covered depression, and 8 covered cognitive impairment; only 1 pertained to Parkinson's disease). High adherence to Mediterranean diet was consistently associated with reduced risk for stroke (RR = 0.71, 95% confidence interval [CI] = 0.57-0.89), depression (RR = 0.68, 95% CI = 0.54-0.86), and cognitive impairment (RR = 0.60, 95% CI = 0.43-0.83). Moderate adherence was similarly associated with reduced risk for depression and cognitive impairment, whereas the protective trend concerning stroke was only marginal. Subgroup analyses highlighted the protective actions of high adherence in terms of reduced risk for ischemic stroke, mild cognitive impairment, dementia, and particularly Alzheimer disease. Meta-regression analysis indicated that the protective effects of Mediterranean diet in stroke prevention seemed more sizeable among males. Concerning depression, the protective effects of high adherence seemed independent of age, whereas the favorable actions of moderate adherence seemed to fade away with more advanced age. INTERPRETATION: Adherence to a Mediterranean diet may contribute to the prevention of a series of brain diseases; this may be of special value given the aging of Western societies. © 2013 American Neurological Association.",
"title": "Mediterranean diet, stroke, cognitive impairment, and depression: A meta-analysis."
},
{
"docid": "MED-2096",
"text": "The key environmental factor involved in caries incidence is fermentable carbohydrates. Because of the high costs of caries treatment, researchers continue to explore dietary control as a promising preventive method. While dietary change has been demonstrated to reduce Streptococcus mutans, a preventive role is expected for \"functional foods\" and dietary habit alterations. The authors consider how recent advances in the understanding of caries pathology can reveal dietary control as a valuable method in promoting a healthy dentition.",
"title": "Emerging science in the dietary control and prevention of dental caries."
},
{
"docid": "MED-1864",
"text": "The effectiveness of Hibiscus sabdariffa L. (HS) in the treatment of risk factors associated with cardiovascular disease is assessed in this review by taking a comprehensive approach to interpreting the randomized clinical trial (RCT) results in the context of the available ethnomedical, phytochemical, pharmacological, and safety and toxicity information. HS decoctions and infusions of calyxes, and on occasion leaves, are used in at least 10 countries worldwide in the treatment of hypertension and hyperlipidemia with no reported adverse events or side effects. HS extracts have a low degree of toxicity with a LD50 ranging from 2,000 to over 5,000 mg/kg/day. There is no evidence of hepatic or renal toxicity as the result of HS extract consumption, except for possible adverse hepatic effects at high doses. There is evidence that HS acts as a diuretic, however in most cases the extract did not significantly influence electrolyte levels. Animal studies have consistently shown that consumption of HS extract reduces blood pressure in a dose dependent manner. In RCTs, the daily consumption of a tea or extract produced from HS calyxes significantly lowered systolic blood pressure (SBP) and diastolic blood pressure (DBP) in adults with pre to moderate essential hypertension and type 2 diabetes. In addition, HS tea was as effective at lowering blood pressure as the commonly used blood pressure medication Captropril, but less effective than Lisinopril. Total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglycerides were lowered in the majority of normolipidemic, hypolipidemic, and diabetic animal models, whereas high-density lipoprotein cholesterol (HDL-C) was generally not affected by the consumption of HS extract. Over half of the RCTs showed that daily consumption of HS tea or extracts had favorable influence on lipid profiles including reduced total cholesterol, LDL-C, triglycerides, as well as increased HDL-C. Anthocyanins found in abundance in HS calyxes are generally considered the phytochemicals responsible for the antihypertensive and hypocholesterolemic effects, however evidence has also been provided for the role of polyphenols and hibiscus acid. A number of potential mechanisms have been proposed to explain the hypotensive and anticholesterol effects, but the most common explanation is the antioxidant effects of the anthocyanins inhibition of LDL-C oxidation, which impedes atherosclerosis, an important cardiovascular risk factor. This comprehensive body of evidence suggests that extracts of HS are promising as a treatment of hypertension and hyperlipidemia, however more high quality animal and human studies informed by actual therapeutic practices are needed to provide recommendations for use that have the potential for widespread public health benefit.",
"title": "Hibiscus sabdariffa L. in the treatment of hypertension and hyperlipidemia: a comprehensive review of animal and human studies"
},
{
"docid": "MED-1955",
"text": "Objective To examine whether an association exists between maternal dietary patterns and risk of preterm delivery. Design Prospective cohort study. Setting Norway, between 2002 and 2008. Participants 66 000 pregnant women (singletons, answered food frequency questionnaire, no missing information about parity or previously preterm delivery, pregnancy duration between 22+0 and 41+6 gestational weeks, no diabetes, first enrolment pregnancy). Main outcome measure Hazard ratio for preterm delivery according to level of adherence to three distinct dietary patterns interpreted as “prudent” (for example, vegetables, fruits, oils, water as beverage, whole grain cereals, fibre rich bread), “Western” (salty and sweet snacks, white bread, desserts, processed meat products), and “traditional” (potatoes, fish). Results After adjustment for covariates, high scores on the “prudent” pattern were associated with significantly reduced risk of preterm delivery hazard ratio for the highest versus the lowest third (0.88, 95% confidence interval 0.80 to 0.97). The prudent pattern was also associated with a significantly lower risk of late and spontaneous preterm delivery. No independent association with preterm delivery was found for the “Western” pattern. The “traditional” pattern was associated with reduced risk of preterm delivery for the highest versus the lowest third (hazard ratio 0.91, 0.83 to 0.99). Conclusion This study showed that women adhering to a “prudent” or a “traditional” dietary pattern during pregnancy were at lower risk of preterm delivery compared with other women. Although these findings cannot establish causality, they support dietary advice to pregnant women to eat a balanced diet including vegetables, fruit, whole grains, and fish and to drink water. Our results indicate that increasing the intake of foods associated with a prudent dietary pattern is more important than totally excluding processed food, fast food, junk food, and snacks.",
"title": "Maternal dietary patterns and preterm delivery: results from large prospective cohort study"
},
{
"docid": "MED-1861",
"text": "INTRODUCTION: Hypertension is a common global health problem with significant mortality and morbidity. Hibiscus sabdariffa is a plant known in many countries and is consumed as hot and cold drinks In addition to its use in folk medicine; it has been suggested as treatment for many conditions including hypertension. OBJECTIVES: The objectives of this review were to examine the evidence of effectiveness and safety of hibiscus in the treatment of hypertension. METHODS: We searched several medical databases (MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and the specialized register of the Cochrane Hypertension Group and the general engine Google) to January 2009. We included randomized controlled trials that had examined Hibiscus's effectiveness and safety in the treatment of primary hypertension in adults. Two authors independently selected the trials for the review, extracted the data, and critically appraised the included studies. RESULTS: Four trials, with a total of 390 patients, met our inclusion criteria. Two studies compared Hibiscus sabdariffa to black tea; one study compared it to captopril and one to lisinopril. The studies found that Hibiscus had greater blood pressure reduction than tea but less than the ACE-inhibitors. However, all studies, except one, were short term and of poor quality with a Jadad scoring of <3 and did not meet international standards. CONCLUSION: The four randomized controlled studies identified in this review do not provide reliable evidence to support recommending Hibiscus sabdariffa for the treatment of primary hypertension in adults. Copyright 2009 Elsevier GmbH. All rights reserved.",
"title": "The effectiveness of Hibiscus sabdariffa in the treatment of hypertension: a systematic review."
},
{
"docid": "MED-1407",
"text": "The Mediterranean tradition offers a cousine rich in colors, aromas and memories, which support the taste and the spirit of those who live in harmony with nature. Everyone is talking about the Mediterranean diet, but few are those who do it properly, thus generating a lot of confusion in the reader. And so for some it coincides with the pizza, others identified it with the noodles with meat sauce, in a mixture of pseudo historical traditions and folklore that do not help to solve the question that is at the basis of any diet: combine and balance the food so as to satisfy the qualitative and quantitative needs of an individual and in a sense, preserves his health through the use of substances that help the body to perform normal vital functions. The purpose of our work is to demonstrate that the combination of taste and health is a goal that can be absolutely carried out by everybody, despite those who believe that only a generous caloric intake can guarantee the goodness of a dish and the satisfaction of the consumers. That should not be an absolute novelty, since the sound traditions of the Mediterranean cuisine we have used for some time in a wide variety of tasty gastronomic choices, from inviting colors and strong scents and absolutely in line with health.",
"title": "The Mediterranean Diet: A History of Health"
},
{
"docid": "MED-3698",
"text": "Purpose Single-variable analyses have associated physical activity, diet, and obesity with survival after breast cancer. This report investigates interactions among these variables. Patients and Methods A prospective study was performed of 1,490 women diagnosed and treated for early-stage breast cancer between 1991 and 2000. Enrollment was an average of 2 years postdiagnosis. Only seven women were lost to follow-up through December 2005. Results In univariate analysis, reduced mortality was weakly associated with higher vegetable-fruit consumption, increased physical activity, and a body mass index that was neither low weight nor obese. In a multivariate Cox model, only the combination of consuming five or more daily servings of vegetables-fruits, and accumulating 540+ metabolic equivalent tasks-min/wk (equivalent to walking 30 minutes 6 d/wk), was associated with a significant survival advantage (hazard ratio, 0.56; 95% CI, 0.31 to 0.98). The approximate 50% reduction in risk associated with these healthy lifestyle behaviors was observed in both obese and nonobese women, although fewer obese women were physically active with a healthy dietary pattern (16% v 30%). Among those who adhered to this healthy lifestyle, there was no apparent effect of obesity on survival. The effect was stronger in women who had hormone receptor–positive cancers. Conclusion A minority of breast cancer survivors follow a healthy lifestyle that includes both recommended intakes of vegetables-fruits and moderate levels of physical activity. The strong protective effect observed suggests a need for additional investigation of the effect of the combined influence of diet and physical activity on breast cancer survival.",
"title": "Greater Survival After Breast Cancer in Physically Active Women With High Vegetable-Fruit Intake Regardless of Obesity"
},
{
"docid": "MED-3709",
"text": "The gut immune system has the challenge of responding to pathogens while remaining relatively unresponsive to food antigens and the commensal microflora. In the developed world, this ability appears to be breaking down, with chronic inflammatory diseases of the gut commonplace in the apparent absence of overt infections. In both mouse and man, mutations in genes that control innate immune recognition, adaptive immunity, and epithelial permeability are all associated with gut inflammation. This suggests that perturbing homeostasis between gut antigens and host immunity represents a critical determinant in the development of gut inflammation and allergy.",
"title": "Immunity, inflammation, and allergy in the gut."
},
{
"docid": "MED-2459",
"text": "BACKGROUND: Free radical-mediated oxidative damage to lipids is thought to be an important process in the pathogenesis of atherosclerosis. Although previous studies have demonstrated a beneficial impact of antioxidant vitamin supplements on lipid peroxidation, the effect of dietary patterns on lipid peroxidation is unknown. METHODS AND RESULTS: During the 3-week run-in period of a randomized trial, 123 healthy individuals were fed a control diet, low in fruits, vegetables, and dairy products, with 37% of calories from fat. Participants were then randomized to consume for 8 weeks: (1) the control diet, (2) a diet rich in fruits and vegetables but otherwise similar to the control diet, and (3) a combination diet rich in fruits, vegetables, and low-fat dairy products and reduced in fat. Serum oxygen radical-absorbing capacity, malondialdehyde (an in vitro measure of lipid peroxidation), and breath ethane (an in vivo measure of lipid peroxidation) were measured at the end of run-in and intervention periods. Between run-in and intervention, mean (95% CI) change in oxygen radical-absorbing capacity (U/mL) was -35 (-93, 13) in the control diet, 26 (-15, 67) in the fruits and vegetables diet (P=0.06 compared with control), and 19 (-22, 54) in the combination diet (P=0.10 compared with control). Median (interquartile range) change in ethane was 0.84 (0.10, 1.59) in the control diet, 0.02 (-0.61, 0.83) in the fruits and vegetables diet (P=0.04 compared with control), and -1.00 (-1.97, 0.25) in the combination diet (P=0.005 compared with control). Change in malondialdehyde did not differ between diets. CONCLUSIONS: This study demonstrates that modification of diet can favorably affect serum antioxidant capacity and protect against lipid peroxidation.",
"title": "Effect of dietary patterns on measures of lipid peroxidation: results from a randomized clinical trial."
},
{
"docid": "MED-3442",
"text": "Gim (Porphyra sp.) and miyeok (Undaria pinnatifida) are the seaweeds most consumed by Koreans. We investigated the association between the intake of gim and miyeok and the risk of breast cancer in a case-control study. Cases were 362 women aged 30-65 years old, who were histologically confirmed to have breast cancer. Controls visiting the same hospital were matched to cases according to their age (sd 2 years) and menopausal status. Food intake was estimated by the quantitative FFQ with 121 items, including gim and miyeok. Conditional logistic regression analysis was used to obtain the OR and corresponding 95 % CI. The average intake and consumption frequency of gim in cases were lower than in controls. The daily intake of gim was inversely associated with the risk of breast cancer (5th v. 1st quintile, OR, 0.48; 95 % CI, 0.27, 0.86; P for trend, 0.026) after adjustment for potential confounders. After stratification analysis was performed according to menopausal status, premenopausal women (5th v. 1st quintile, OR, 0.44; 95 % CI, 0.24, 0.80; P for trend, 0.007) and postmenopausal women (5th v. 1st quintile, OR, 0.32; 95 % CI, 0.13, 0.80; P for trend, 0.06) showed similar inverse associations between gim intake and the risk of breast cancer after an adjustment for potential confounders except dietary factors. Miyeok consumption did not have any significant associations with breast cancer. These results suggest that high intake of gim may decrease the risk of breast cancer.",
"title": "A case-control study on seaweed consumption and the risk of breast cancer."
},
{
"docid": "MED-2094",
"text": "INTRODUCTION: An increasing number of people all around the world are turning to the nature by using the natural herbal products in both prophylaxes and treatment of different diseases. Green tea with active chemical ingredients posses diverse pharmacological properties that include anti-inflammatory, anticariogenic, antioxidant and antibacterial effects. AIMS: To assess the possible protective properties of green tea on oral health. METHODS: The researchers used the following measurements: Streptococcus mutans count in saliva and plaque, Salivary and plaque pH values, Gingival Bleeding Index (GBI). The above-mentioned measurements were applied to a sample consists of 25 subjects before and after rinsing with green tea for 5 min (short-term study). While, S. mutans count for saliva and plaque and GBI measurements, this experimental intervention study was carried out in the El-Azhar University dental clinic. RESULTS: The results of this study showed that there was a statistically significant difference among subjects pre- and post-rinsing with 2% green tea for 5 min concerning S. mutans count in saliva and plaque, salivary and plaque pH values and GBI. CONCLUSION: This study supports the effectiveness of local application of green tea as antibacterial and anticariogenic material as it decreases the acidity of the saliva and plaque, so it is a cost-effective caries prevention measures especially in developing countries. © 2009 John Wiley & Sons A/S.",
"title": "A pilot study of the role of green tea use on oral health."
},
{
"docid": "MED-4823",
"text": "Background Previous research relating dietary fat, a modifiable risk factor, to pancreatic cancer has been inconclusive. Methods We prospectively analyzed the association between intakes of fat, fat subtypes, and fat food sources and exocrine pancreatic cancer in the National Institutes of Health–AARP Diet and Health Study, a US cohort of 308 736 men and 216 737 women who completed a 124-item food frequency questionnaire in 1995–1996. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models, with adjustment for energy intake, smoking history, body mass index, and diabetes. Statistical tests were two-sided. Results Over an average follow-up of 6.3 years, 865 men and 472 women were diagnosed with exocrine pancreatic cancer (45.0 and 34.5 cases per 100 000 person-years, respectively). After multivariable adjustment and combination of data for men and women, pancreatic cancer risk was directly related to the intakes of total fat (highest vs lowest quintile, 46.8 vs 33.2 cases per 100 000 person-years, HR = 1.23, 95% CI = 1.03 to 1.46; Ptrend = .03), saturated fat (51.5 vs 33.1 cases per 100 000 person-years, HR = 1.36, 95% CI = 1.14 to 1.62; Ptrend < .001), and monounsaturated fat (46.2 vs 32.9 cases per 100 000 person-years, HR = 1.22, 95% CI = 1.02 to 1.46; Ptrend = .05) but not polyunsaturated fat. The associations were strongest for saturated fat from animal food sources (52.0 vs 32.2 cases per 100 000 person-years, HR = 1.43, 95% CI = 1.20 to 1.70; Ptrend < .001); specifically, intakes from red meat and dairy products were both statistically significantly associated with increased pancreatic cancer risk (HR = 1.27 and 1.19, respectively). Conclusion In this large prospective cohort with a wide range of intakes, dietary fat of animal origin was associated with increased pancreatic cancer risk.",
"title": "Dietary Fatty Acids and Pancreatic Cancer in the NIH-AARP Diet and Health Study"
},
{
"docid": "MED-1366",
"text": "My concern about diet as a public health problem began in the early 1950s in Naples, where we observed very low incidences of coronary heart disease associated with what we later came to call the \"good Mediterranean diet.\" The heart of this diet is mainly vegetarian, and differs from American and northern European diets in that it is much lower in meat and dairy products and uses fruit for dessert. These observations led to our subsequent research in the Seven Countries Study, in which we demonstrated that saturated fat is the major dietary villain. Today, the healthy Mediterranean diet is changing and coronary heart disease is no longer confined to medical textbooks. Our challenge is to persuade children to tell their parents to eat as Mediterraneans do.",
"title": "Mediterranean diet and public health: personal reflections."
},
{
"docid": "MED-1185",
"text": "Endogenous sulfite is generated as a consequence of the body's normal processing of sulfur-containing amino acids. Sulfites occur as a consequence of fermentation and also occur naturally in a number of foods and beverages. As food additives, sulfiting agents were first used in 1664 and approved in the United States as long ago as the 1800s. With such long experience with their use, it is easy to understand why these substances have been regarded as safe. They are currently used for a variety of preservative properties, including controlling microbial growth, preventing browning and spoilage, and bleaching some foods. It is estimated that up to 500,000 (< .05% of the population) sulfite-sensitive individuals live in the United States. Sulfite sensitivity occurs most often in asthmatic adults--predominantly women; it is uncommonly reported in preschool children. Adverse reactions to sulfites in nonasthmatics are extremely rare. Asthmatics who are steroid-dependent or who have a higher degree of airway hyperreactivity may be at greater risk of experiencing a reaction to sulfite-containing foods. Even within this limited population, sulfite sensitivity reactions vary widely, ranging from no reaction to severe. The majority of reactions are mild. These manifestations may include dermatologic, respiratory, or gastrointestinal signs and symptoms. Severe nonspecific signs and symptoms occur less commonly. Broncho-constriction is the most common sensitivity response in asthmatics. The precise mechanisms of the sensitivity responses have not been completely elucidated. Inhalation of sulfur dioxide (SO2) generated in the stomach following ingestion of sulfite-containing foods or beverages, a deficiency in a mitochondrial enzyme, and an IgE-mediated immune response have all been implicated.(ABSTRACT TRUNCATED AT 250 WORDS)",
"title": "Sulfite sensitivity: significance in human health."
},
{
"docid": "MED-1954",
"text": "The behaviour problems of children born preterm at school age are well known, but there have been few studies on the behaviour problems of preterm-born infants during infancy and at preschool age. Fourteen cohort studies published in PubMed and PsycINFO between 2000 and 2012 were reviewed with a focus on the type, occurrence, comorbidity, stability, prediction, perinatal, social, and relational risk factors for behaviour problems of preterm-born children in infancy (0-2y) and at preschool age (3-5y). The relational risk factor was considered in an additional four papers. Very-preterm, very-low-birthweight, and moderately-preterm children, in both age groups, show more behaviour problems than term-born comparison children even after perinatal and social risk factors and cognitive performance have been controlled for. Poor social/interactive skills, poor behavioural and emotional self-regulation, emotional difficulties, and reduced attention are the most common behaviour problems. Behaviour problems in infancy are predictive of later behaviour problems and they should be included in follow-up programmes. © The Authors. Developmental Medicine & Child Neurology © 2013 Mac Keith Press.",
"title": "Preterm birth and behaviour problems in infants and preschool-age children: a review of the recent literature."
},
{
"docid": "MED-1811",
"text": "BACKGROUND: A growing number of preclinical studies have demonstrated that curcumin could be a promising anticancer drug; however, poor bioavailability has been the major obstacle for its clinical application. To overcome this problem, we developed a new form of curcumin (Theracurmin) and reported high plasma curcumin levels could be safely achieved after a single administration of Theracurmin in healthy volunteers. In this study, we aimed to evaluate the safety of repetitive administration of Theracurmin in cancer patients. METHODS: Pancreatic or biliary tract cancer patients who failed standard chemotherapy were eligible for this study. Based on our previous pharmacokinetic study, we selected Theracurmin containing 200 mg of curcumin (Level 1) as a starting dose, and the dose was safely escalated to Level 2, which contained 400 mg of curcumin. Theracurmin was orally administered every day with standard gemcitabine-based chemotherapy. In addition to safety and pharmacokinetics data, NF-κB activity, cytokine levels, efficacy, and quality-of-life score were evaluated. RESULTS: Ten patients were assigned to level 1 and six were to level 2. Peak plasma curcumin levels (median) after Theracurmin administration were 324 ng/mL (range, 47-1,029 ng/mL) at Level 1 and 440 ng/mL (range, 179-1,380 ng/mL) at Level 2. No unexpected adverse events were observed and 3 patients safely continued Theracurmin administration for >9 months. CONCLUSIONS: Repetitive systemic exposure to high concentrations of curcumin achieved by Theracurmin did not increase the incidence of adverse events in cancer patients receiving gemcitabine-based chemotherapy.",
"title": "A phase I study investigating the safety and pharmacokinetics of highly bioavailable curcumin (Theracurmin) in cancer patients."
},
{
"docid": "MED-1656",
"text": "Background Low back pain (LBP) is common in children and adolescents, and it is becoming a public health concern. In recent years there has been a considerable increase in research studies that examine the prevalence of LBP in this population, but studies exhibit great variability in the prevalence rates reported. The purpose of this research was to examine, by means of a meta-analytic investigation, the prevalence rates of LBP in children and adolescents. Methods Studies were located from computerized databases (ISI Web of Knowledge, MedLine, PEDro, IME, LILACS, and CINAHL) and other sources. The search period extended to April 2011. To be included in the meta-analysis, studies had to report a prevalence rate (whether point, period or lifetime prevalence) of LBP in children and/or adolescents (≤ 18 years old). Two independent researchers coded the moderator variables of the studies, and extracted the prevalence rates. Separate meta-analyses were carried out for the different types of prevalence in order to avoid dependence problems. In each meta-analysis, a random-effects model was assumed to carry out the statistical analyses. Results A total of 59 articles fulfilled the selection criteria. The mean point prevalence obtained from 10 studies was 0.120 (95% CI: 0.09 and 0.159). The mean period prevalence at 12 months obtained from 13 studies was 0.336 (95% CI: 0.269 and 0.410), whereas the mean period prevalence at one week obtained from six studies was 0.177 (95% CI: 0.124 and 0.247). The mean lifetime prevalence obtained from 30 studies was 0.399 (95% CI: 0.342 and 0.459). Lifetime prevalence exhibited a positive, statistically significant relationship with the mean age of the participants in the samples and with the publication year of the studies. Conclusions The most recent studies showed higher prevalence rates than the oldest ones, and studies with a better methodology exhibited higher lifetime prevalence rates than studies that were methodologically poor. Future studies should report more information regarding the definition of LBP and there is a need to improve the methodological quality of studies.",
"title": "Prevalence of low back pain in children and adolescents: a meta-analysis"
},
{
"docid": "MED-2967",
"text": "The hypothesis that plasma chylomicrons in persons who ingest a cholesterol-rich diet are atherogenic is evaluated. Evidence is presented that in humans, and experimental animals, chylomicron remnants as well as low-density lipoproteins are taken up by arterial cells. In persons who do not have familial hyperlipoproteinemia, atherogenesis may occur during the postprandial period. Research directions that may contribute to the evaluation of chylomicron remnants as a risk factor for atherogenesis are discussed. Lipoprotein studies after administration of a test meal containing fat and cholesterol are urgently needed.",
"title": "Atherogenesis: a postprandial phenomenon."
},
{
"docid": "MED-3277",
"text": "Methionine dependence is a metabolic defect that occurs in many human tumor cell lines but not normal in unestablished cell strains. Methionine-dependent tumor cell lines are unable to proliferate and arrest in the late S/G2 phase of the cell cycle when methionine is replaced by its immediate precursor homocysteine in the culture medium (MET-HCY+ medium). However, it is not known whether methionine dependence occurs in fresh patient tumors as it does in cell lines. In order to determine whether methionine dependence occurs in fresh patient tumors as well as whether methionine dependence occurs in fresh patient tumors as well as in cell lines we took advantage of the technique of sponge-gel-supported histoculture to grow tumors directly from surgery. We then measured nuclear DNA content by image analysis to determine the cell cycle position in MET-HCY+ compared to MET+HCY- medium in 21 human patient tumors. Human tumor cell lines found to be methionine dependent by cell count were used as positive controls and were found to have marked reduction of cells in G1 compared to total cells in the cell cycle in MET-HCY+ medium with respect to the G1: total cell ratio in MET+HCY- medium. Therefore late cell cycle arrest was used as a marker of methionine dependence for histocultured patient tumors. We found that 5 human tumors of 21, including tumors of the colon, breast, ovary, prostate, and a melanoma, were methionine dependent based on cell cycle analysis. These data on fresh human tumors indicate that methionine dependence may frequently occur in the cancer patient population. Implications for potential therapy based on methionine dependence are discussed.",
"title": "Expression of the biochemical defect of methionine dependence in fresh patient tumors in primary histoculture."
},
{
"docid": "MED-1498",
"text": "Many studies have documented the role of risk and protective factors for late life dementing illnesses, particularly Alzheimer's disease. A \"Systematic Review\" from the US Agency for Healthcare Research and Quality and the National Institute on Aging concluded that because the overall quality of evidence was low, recommendations for public health could not be made. In order to gain evidence for the efficacy of lifestyle interventions, we propose a \"Modest Proposal\" to study 10,000 subjects over 40 years randomly assigned to groups of low or high saturated fat in the diet, head injury, and high or low levels of mental activity, physical activity, or inactivity as well as smoking or non-smoking. This proposed study cannot be accomplished. The \"Modest Proposal\" illustrates that the absence of definitive evidence should not restrict physicians from making reasonable recommendations based on the evidence that is available.",
"title": "A modest proposal for a longitudinal study of dementia prevention (with apologies to Jonathan Swift, 1729)."
},
{
"docid": "MED-4236",
"text": "PURPOSE: We reviewed recent literature and treatment guidelines regarding the prevalence, pathophysiology, and management of BPO related to BPH; and management of lower urinary tract symptoms secondary to BPH. MATERIALS AND METHODS: Published literature and current treatment concepts were reviewed regarding the diagnosis and treatment options for BPO. RESULTS: BPH is a histological diagnosis that can contribute to medical problems, including enlargement of the prostate and BPO. These conditions should be treated only if the symptoms are troublesome, there is considerable risk of progression, and/or cancer is suspected. Very effective medical and surgical options are available to treat BPO and improve patient quality of life. CONCLUSIONS: BPO is highly treatable, but should be managed in close collaboration with the patient. Pharmacological agents and minimally invasive procedures, when appropriate, are generally preferred to more invasive surgery. Patients with mild or moderate symptoms usually can be treated by a primary care physician; more complicated cases should be referred to a urologist for evaluation and management.",
"title": "Benign prostatic hyperplasia in primary care: what you need to know."
},
{
"docid": "MED-3283",
"text": "Available information indicates that long-lived mammals have low rates of reactive oxygen species (ROS) generation and oxidative damage at their mitochondria. On the other hand, many studies have consistently shown that dietary restriction (DR) in rodents also decreases mitochondrial ROS (mtROS) production and oxidative damage to mitochondrial DNA and proteins. It has been observed that protein restriction also decreases mtROS generation and oxidative stress in rat liver, whereas neither carbohydrate nor lipid restriction change these parameters. This is interesting because protein restriction also increases maximum longevity in rodents (although to a lower extent than DR) and is a much more practicable intervention for humans than DR, whereas neither carbohydrate nor lipid restriction seem to change rodent longevity. Moreover, it has been found that isocaloric methionine restriction also decreases mtROS generation and oxidative stress in rodent tissues, and this manipulation also increases maximum longevity in rats and mice. In addition, excessive dietary methionine also increases mtROS generation in rat liver. These studies suggest that the reduced intake of dietary methionine can be responsible for the decrease in mitochondrial ROS generation and the ensuing oxidative damage that occurs during DR, as well as for part of the increase in maximum longevity induced by this dietary manipulation. In addition, the mean intake of proteins (and thus methionine) of Western human populations is much higher than needed. Therefore, decreasing such levels to the recommended ones has a great potential to lower tissue oxidative stress and to increase healthy life span in humans while avoiding the possible undesirable effects of DR diets.",
"title": "Lowered methionine ingestion as responsible for the decrease in rodent mitochondrial oxidative stress in protein and dietary restriction possible i..."
},
{
"docid": "MED-1657",
"text": "OBJECTIVES—To study the prevalence of arterial diseases in the arteries supplying the lumbar spine and their relation to other vascular diseases, as well as to chronic low back pain. METHODS—Five pairs of the lumbar arteries and the middle sacral artery were evaluated from 140 postmortem aortograms, performed in connection with routine medicolegal necropsies on subjects ranging from 16 to 89 years of age. For information about low back pain history, a close relative of each of the deceased was interviewed two to four weeks after the necropsy. RESULTS—Twenty one (22%) men and nine (20%) women had occluded arteries, and an additional 33 (35%) men and 17 (38%) women had narrowed arteries. The mean age for men with occluded or narrowed arteries, or both, was 50 years and for women 59 years. Most of the stenotic changes were seen at the orifices or in the first part of the arteries. The middle sacral artery was most often affected, followed by the fourth lumbar arteries. The number of collateral arteries increased with occluded (p <0.001) and narrowed arteries (p = 0.001). Stenotic lumbar/middle sacral arteries were found, on average, five years earlier than atherosclerosis of the coronary arteries. Subjects with one or more occluded/narrowed arteries were 8.5 times more likely to have suffered from chronic (that is, three months or longer) low back pain at some time during their life than were those without such findings (odds ratio adjusted for age and sex 8.5; 95% confidence intervals 2.9, 24; p <0.001). CONCLUSIONS—The study shows that the lumbar and middle sacral arteries frequently become obliterated by atheromatous lesions during adult life, and that obliteration of these arteries is more common in subjects with a history of chronic back pain than in those without.",
"title": "Prevalence of stenotic changes in arteries supplying the lumbar spine. A postmortem angiographic study on 140 subjects"
},
{
"docid": "MED-2581",
"text": "A hospital-based case-control study of diet and colorectal cancer was conducted among Chinese in Singapore (who constitute 77% of the population). A total of 203 cases and 425 controls were included. A history of the usual dietary intake one year prior to interview was taken using a quantitative food frequency questionnaire. Daily intakes of nutrients and selected food items were computed and stratified by tertiles of the control range, to assess risk in low-, medium- and high-intake categories. Effects were adjusted in analysis for age, sex, Chinese dialect group and occupation. For cancers of colon and rectum combined, significant observations were a protective effect of high cruciferous vegetable intake (OR = 0.50, p less than 0.01) and a predisposing effect of a high meat/vegetable consumption ratio (OR = 1.77, p less than 0.05). Similar results were observed for colon cancer alone. For rectal cancer alone (only 71 cases), significant (p less than 0.05) protective effects were observed for high intakes of protein (OR = 0.61), fibre (OR = 0.46), beta-carotene (OR = 0.54), cruciferous vegetables (OR = 0.51) and total vegetables (OR = 0.51). When further assessed by multiple logistic regression, tests for trend and assessment of risk in the extreme highest and lowest quintiles of the control range, the factors consistently significant were cruciferous vegetable intake and the meat/vegetable ratio. A particularly high relative risk was also noted in association with low coffee consumption (OR = 1.59, with p less than 0.05 for trend). No consistent trends were noted for fat or fibre intakes. For non-dietary variables investigated, a history of cholecystectomy increased the risk of both cancers combined (OR = 3.43, p less than 0.05) and colon cancer alone (OR = 4.39, p less than 0.01). This study in an Asian population of countries of Southern and Eastern Asia newly undergoing industrialization and in which rapid economic change is reflected in changing cancer patterns, suggests that the protective effects of certain dietary constituents, notably the cruciferous vegetables, may be more important than the hitherto stressed carcinogenic potential of fat and protein.",
"title": "Colorectal cancer and diet in an Asian population--a case-control study among Singapore Chinese."
},
{
"docid": "MED-2090",
"text": "Taking into consideration genetic damage plays an important role in carcinogenesis, the purpose of this paper is to provide an overview on the genotoxic potential of some endodontic compounds currently used in dentistry, such as formocresol, paramonochlorophenol, calcium hydroxide, resin-based sealers, phenolic compounds, chlorhexidine, mineral trioxide aggregate, and others. Some of these compounds appear capable of exerting noxious activity on the genetic material. The action mechanisms are discussed. Therefore, this is an area that warrants investigation since the estimation of risk of these substances with respect to genotoxicity will be added to those used for regulatory purposes in improving oral health and preventing oral carcinogenesis.",
"title": "Do endodontic compounds induce genetic damage? A comprehensive review."
},
{
"docid": "MED-1489",
"text": "PURPOSE: Plant-based nutrition achieved coronary artery disease (CAD) arrest and reversal in a small study. However, there was skepticism that this approach could succeed in a larger group of patients. The purpose of our follow-up study was to define the degree of adherence and outcomes of 198 consecutive patient volunteers who received counseling to convert from a usual diet to plant-based nutrition. METHODS: We followed 198 consecutive patients counseled in plant-based nutrition. These patients with established cardiovascular disease (CVD) were interested in transitioning to plant-based nutrition as an adjunct to usual cardiovascular care. We considered participants adherent if they eliminated dairy, fish, and meat, and added oil. RESULTS: Of the 198 patients with CVD, 177 (89%) were adherent. Major cardiac events judged to be recurrent disease totaled one stroke in the adherent cardiovascular participants—a recurrent event rate of .6%, significantly less than reported by other studies of plant-based nutrition therapy. Thirteen of 21 (62%) nonadherent participants experienced adverse events. CONCLUSION: Most of the volunteer patients with CVD responded to intensive counseling, and those who sustained plant-based nutrition for a mean of 3.7 years experienced a low rate of subsequent cardiac events. This dietary approach to treatment deserves a wider test to see if adherence can be sustained in broader populations. Plant-based nutrition has the potential for a large effect on the CVD epidemic.",
"title": "A way to reverse CAD?"
},
{
"docid": "MED-3282",
"text": "BACKGROUND AND AIMS: The mechanisms of cancer cell growth and metastasis are still not entirely understood, especially from the viewpoint of chemical reactions in tumours. Glycolytic metabolism is markedly accelerated in cancer cells, causing the accumulation of glucose (a reducing sugar) and methionine (an amino acid), which can non-enzymatically react and form carcinogenic substances. There is speculation that this reaction produces gaseous sulfur-containing compounds in tumour tissue. The aims of this study were to clarify the products in tumour and to investigate their effect on tumour proliferation. METHODS: Products formed in the reaction between glucose and methionine or its metabolites were analysed in vitro using gas chromatography. Flatus samples from patients with colon cancer and exhaled air samples from patients with lung cancer were analysed using near-edge x-ray fine adsorption structure spectroscopy and compared with those from healthy individuals. The tumour proliferation rates of mice into which HT29 human colon cancer cells had been implanted were compared with those of mice in which the cancer cells were surrounded by sodium hyaluronate gel to prevent diffusion of gaseous material into the healthy cells. RESULTS: Gaseous sulfur-containing compounds such as methanethiol and hydrogen sulfide were produced when glucose was allowed to react with methionine or its metabolites homocysteine or cysteine. Near-edge x-ray fine adsorption structure spectroscopy showed that the concentrations of sulfur-containing compounds in the samples of flatus from patients with colon cancer and in the samples of exhaled air from patients with lung cancer were significantly higher than in those from healthy individuals. Animal experiments showed that preventing the diffusion of sulfur-containing compounds had a pronounced antitumour effect. CONCLUSIONS: Gaseous sulfur-containing compounds are the main products in tumours and preventing the diffusion of these compounds reduces the tumour proliferation rate, which suggests the possibility of a new approach to cancer treatment.",
"title": "Generation of gaseous sulfur-containing compounds in tumour tissue and suppression of gas diffusion as an antitumour treatment."
},
{
"docid": "MED-2512",
"text": "Ageing is a challenge for any living organism and human longevity is a complex phenotype. With increasing life expectancy, maintaining long-term health, functionality and well-being during ageing has become an essential goal. To increase our understanding of how ageing works, it may be advantageous to analyze the phenotype of centenarians, perhaps one of the best examples of successful ageing. Healthy ageing involves the interaction between genes, the environment, and lifestyle factors, particularly diet. Besides evaluating specific gene-environment interactions in relation to exceptional longevity, it is important to focus attention on modifiable lifestyle factors such as diet and nutrition to achieve extension of health span. Furthermore, a better understanding of human longevity may assist in the design of strategies to extend the duration of optimal human health. In this article we briefly discuss relevant topics on ageing and longevity with particular focus on dietary patterns of centenarians and nutrient-sensing pathways that have a pivotal role in the regulation of life span. Finally, we also discuss the potential role of Nrf2 system in the pro-ageing signaling emphasizing its phytohormetic activation.",
"title": "Extending healthy ageing: nutrient sensitive pathway and centenarian population"
},
{
"docid": "MED-1873",
"text": "Research finding on the composition of macronutrient intakes on body weight has not been consistent. Furthermore, little research has examined the impact of subcomponents of macronutrients such as saturated fat or plant protein on body weight. The purpose of this report was to examine the impact of saturated fat, animal and plant protein, and other macronutrient intakes at the end of an intensive intervention on subsequent follow-up body weight. This is a secondary, observational data analysis using data from PREMIER, an 18-month randomized clinical trial that enrolled a total of 810 participants. Participants completed group and individual sessions designed to help them improve blood pressure (BP) control by making lifestyle changes. Dietary intakes were assessed by two 24-h diet recalls at baseline, 6, and 18 months. Body weight and physical fitness were monitored regularly. Regression models were used to examine the impact of animal or plant protein and other macronutrient intakes on subsequent body weight. After controlling for potential confounders, none of the calorie-contributing nutrient intakes at baseline was associated with subsequent weight at 6 or 18 months. However, a greater intake of saturated fat at 6 months was associated with higher weight at 18 months (P = 0.002). A greater intake of plant protein at 6 month was marginally associated with lower absolute weight at 18 month (P = 0.069). We conclude that macronutrient intakes before the intervention were not associated with subsequent body weight at 6 or 18 months. However, a lower saturated fat intake achieved after 6-month intervention predicts a lower body weight at 18 months and thus greater weight-loss maintenance.",
"title": "Dietary saturated fat intake is negatively associated with weight maintenance among the PREMIER participants."
},
{
"docid": "MED-3801",
"text": "21 patients with severe persistent cyclical mastopathy of at least 5 years' duration were randomised to a control group who received general dietary advice or to an intervention group who were taught how to reduce the fat content of their diet to 15% of calories while increasing complex carbohydrate consumption to maintain caloric intake. Both groups were followed for 6 months with food records and measurement of plasma hormone and lipid levels. Severity of symptoms was recorded with daily diaries and patients were assessed at the beginning and end of the study by a physician who was unaware of their dietary regimen. After 6 months there was a significant reduction in the intervention group in the severity of premenstrual breast tenderness and swelling. Physical examination showed reduced breast swelling, tenderness, and nodularity in 6 of 10 patients in the intervention group and 2 of 9 patients in the control group.",
"title": "Effect of a low-fat high-carbohydrate diet on symptoms of cyclical mastopathy."
},
{
"docid": "MED-5303",
"text": "IMPORTANCE: Understanding the major health problems in the United States and how they are changing over time is critical for informing national health policy. OBJECTIVES: To measure the burden of diseases, injuries, and leading risk factors in the United States from 1990 to 2010 and to compare these measurements with those of the 34 countries in the Organisation for Economic Co-operation and Development (OECD) countries. DESIGN: We used the systematic analysis of descriptive epidemiology of 291 diseases and injuries, 1160 sequelae of these diseases and injuries, and 67 risk factors or clusters of risk factors from 1990 to 2010 for 187 countries developed for the Global Burden of Disease 2010 Study to describe the health status of the United States and to compare US health outcomes with those of 34 OECD countries. Years of life lost due to premature mortality (YLLs) were computed by multiplying the number of deaths at each age by a reference life expectancy at that age. Years lived with disability (YLDs) were calculated by multiplying prevalence (based on systematic reviews) by the disability weight (based on population-based surveys) for each sequela; disability in this study refers to any short- or long-term loss of health. Disability-adjusted life-years (DALYs) were estimated as the sum of YLDs and YLLs. Deaths and DALYs related to risk factors were based on systematic reviews and meta-analyses of exposure data and relative risks for risk-outcome pairs. Healthy life expectancy (HALE) was used to summarize overall population health, accounting for both length of life and levels of ill health experienced at different ages. RESULTS: US life expectancy for both sexes combined increased from 75.2 years in 1990 to 78.2 years in 2010; during the same period, HALE increased from 65.8 years to 68.1 years. The diseases and injuries with the largest number of YLLs in 2010 were ischemic heart disease, lung cancer, stroke, chronic obstructive pulmonary disease, and road injury. Age-standardized YLL rates increased for Alzheimer disease, drug use disorders, chronic kidney disease, kidney cancer, and falls. The diseases with the largest number of YLDs in 2010 were low back pain, major depressive disorder, other musculoskeletal disorders, neck pain, and anxiety disorders. As the US population has aged, YLDs have comprised a larger share of DALYs than have YLLs. The leading risk factors related to DALYs were dietary risks, tobacco smoking, high body mass index, high blood pressure, high fasting plasma glucose, physical inactivity, and alcohol use. Among 34 OECD countries between 1990 and 2010, the US rank for the age-standardized death rate changed from 18th to 27th, for the age-standardized YLL rate from 23rd to 28th, for the age-standardized YLD rate from 5th to 6th, for life expectancy at birth from 20th to 27th, and for HALE from 14th to 26th. CONCLUSIONS AND RELEVANCE: From 1990 to 2010, the United States made substantial progress in improving health. Life expectancy at birth and HALE increased, all-cause death rates at all ages decreased, and age-specific rates of years lived with disability remained stable. However, morbidity and chronic disability now account for nearly half of the US health burden, and improvements in population health in the United States have not kept pace with advances in population health in other wealthy nations.",
"title": "The state of US health, 1990-2010: burden of diseases, injuries, and risk factors."
},
{
"docid": "MED-1210",
"text": "Poor diet quality is thought to be a leading risk factor for years of life lost. We examined how scores on 4 commonly used diet quality indices-the Healthy Eating Index 2010 (HEI), the Alternative Healthy Eating Index 2010 (AHEI), the Alternate Mediterranean Diet (aMED), and the Dietary Approaches to Stop Hypertension (DASH)-are related to the risks of death from all causes, cardiovascular disease (CVD), and cancer among postmenopausal women. Our prospective cohort study included 63,805 participants in the Women's Health Initiative Observational Study (from 1993-2010) who completed a food frequency questionnaire at enrollment. Cox proportional hazards models were fit using person-years as the underlying time metric. We estimated multivariate hazard ratios and 95% confidence intervals for death associated with increasing quintiles of diet quality index scores. During 12.9 years of follow-up, 5,692 deaths occurred, including 1,483 from CVD and 2,384 from cancer. Across indices and after adjustment for multiple covariates, having better diet quality (as assessed by HEI, AHEI, aMED, and DASH scores) was associated with statistically significant 18%-26% lower all-cause and CVD mortality risk. Higher HEI, aMED, and DASH (but not AHEI) scores were associated with a statistically significant 20%-23% lower risk of cancer death. These results suggest that postmenopausal women consuming a diet in line with a priori diet quality indices have a lower risk of death from chronic disease. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.",
"title": "Comparing indices of diet quality with chronic disease mortality risk in postmenopausal women in the Women's Health Initiative Observational Study:..."
},
{
"docid": "MED-2112",
"text": "Medical students in the United States are taught little about nutrition and dietetics. Worse yet, their training biases them against the studies that show the power of dietary approaches to managing disease. The current approach to evidence-based medicine encourages physicians to ignore any information that does not come from a double-blind, randomized controlled trial. Yet human beings cannot be blinded to a dietary intervention. As a result, physicians are biased toward drug treatments and against dietary interventions for the management of chronic disease. Copyright © 2013 Elsevier Ltd. All rights reserved.",
"title": "How evidence-based medicine biases physicians against nutrition."
},
{
"docid": "MED-3231",
"text": "This review looks at the role of an alkaline diet in health. Pubmed was searched looking for articles on pH, potential renal acid loads, bone health, muscle, growth hormone, back pain, vitamin D and chemotherapy. Many books written in the lay literature on the alkaline diet were also reviewed and evaluated in light of the published medical literature. There may be some value in considering an alkaline diet in reducing morbidity and mortality from chronic diseases and further studies are warranted in this area of medicine.",
"title": "The Alkaline Diet: Is There Evidence That an Alkaline pH Diet Benefits Health?"
},
{
"docid": "MED-4686",
"text": "There is ample reason to believe that diets rich in phytochemicals provide protection from vascular diseases and many cancers; direct antioxidant activity as well as modulation of enzyme expression or hormone activity contribute to this effect. Phytochemicals derived from diverse foods presumably can interact additively and (possibly) synergistically; thus, the total dietary load of phytochemicals may have important implications for health. As a means of very roughly quantifying this load, a \"phytochemical index\" (PI) is proposed, defined as the percent of dietary calories derived from foods rich in phytochemicals. Calories derived from fruits, vegetables (excluding potatoes), legumes, whole grains, nuts, seeds, fruit/vegetable juices, soy products, wine, beer, and cider - and foods compounded therefrom - would be counted in this index. Partial credit could be given for antioxidant-rich extra virgin olive oil. Other added oils, refined sugars, refined grains, potato products, hard liquors, and animal products - regrettably, the chief sources of calories in typical Western diets - would be excluded. Although the PI would provide only a very rough approximation of the quantity or quality of phytochemical nutrition, it nonetheless could aid epidemiologists in exploring the health consequences of diets high in phytochemical-rich plant foods, and could also help clinical nutritionists in their efforts to improve the phytochemical nutrition of their clients.",
"title": "Proposal for a dietary \"phytochemical index\"."
},
{
"docid": "MED-1402",
"text": "OBJECTIVE: To update previous meta-analyses of cohort studies that investigated the association between the Mediterranean diet and health status and to utilize data coming from all of the cohort studies for proposing a literature-based adherence score to the Mediterranean diet. DESIGN: We conducted a comprehensive literature search through all electronic databases up to June 2013. SETTING: Cohort prospective studies investigating adherence to the Mediterranean diet and health outcomes. Cut-off values of food groups used to compute the adherence score were obtained. SUBJECTS: The updated search was performed in an overall population of 4 172 412 subjects, with eighteen recent studies that were not present in the previous meta-analyses. RESULTS: A 2-point increase in adherence score to the Mediterranean diet was reported to determine an 8 % reduction of overall mortality (relative risk = 0·92; 95 % CI 0·91, 0·93), a 10 % reduced risk of CVD (relative risk = 0·90; 95 % CI 0·87, 0·92) and a 4 % reduction of neoplastic disease (relative risk = 0·96; 95 % CI 0·95, 0·97). We utilized data coming from all cohort studies available in the literature for proposing a literature-based adherence score. Such a score ranges from 0 (minimal adherence) to 18 (maximal adherence) points and includes three different categories of consumption for each food group composing the Mediterranean diet. CONCLUSIONS: The Mediterranean diet was found to be a healthy dietary pattern in terms of morbidity and mortality. By using data from the cohort studies we proposed a literature-based adherence score that can represent an easy tool for the estimation of adherence to the Mediterranean diet also at the individual level.",
"title": "Mediterranean diet and health status: an updated meta-analysis and a proposal for a literature-based adherence score."
},
{
"docid": "MED-2501",
"text": "Amino acids play fundamental roles in the cell both as the building blocks of new proteins and as metabolic precursors. To adapt to their limitation during periods of protein starvation, multiple adaptive mechanisms have evolved, including a rapid cessation of new protein synthesis, an increase in amino acid biosynthesis and transport, and autophagy. Here, we discuss what we currently know about how amino acid limitation is sensed, and how this sensing might be transmitted to mTORC1 to regulate protein synthesis and autophagy. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Amino acid sensing and regulation of mTORC1."
},
{
"docid": "MED-2951",
"text": "Background A plant-based diet protects against chronic oxidative stress-related diseases. Dietary plants contain variable chemical families and amounts of antioxidants. It has been hypothesized that plant antioxidants may contribute to the beneficial health effects of dietary plants. Our objective was to develop a comprehensive food database consisting of the total antioxidant content of typical foods as well as other dietary items such as traditional medicine plants, herbs and spices and dietary supplements. This database is intended for use in a wide range of nutritional research, from in vitro and cell and animal studies, to clinical trials and nutritional epidemiological studies. Methods We procured samples from countries worldwide and assayed the samples for their total antioxidant content using a modified version of the FRAP assay. Results and sample information (such as country of origin, product and/or brand name) were registered for each individual food sample and constitute the Antioxidant Food Table. Results The results demonstrate that there are several thousand-fold differences in antioxidant content of foods. Spices, herbs and supplements include the most antioxidant rich products in our study, some exceptionally high. Berries, fruits, nuts, chocolate, vegetables and products thereof constitute common foods and beverages with high antioxidant values. Conclusions This database is to our best knowledge the most comprehensive Antioxidant Food Database published and it shows that plant-based foods introduce significantly more antioxidants into human diet than non-plant foods. Because of the large variations observed between otherwise comparable food samples the study emphasizes the importance of using a comprehensive database combined with a detailed system for food registration in clinical and epidemiological studies. The present antioxidant database is therefore an essential research tool to further elucidate the potential health effects of phytochemical antioxidants in diet.",
"title": "The total antioxidant content of more than 3100 foods, beverages, spices, herbs and supplements used worldwide"
},
{
"docid": "MED-1193",
"text": "Summary Background Statins reduce LDL cholesterol and prevent vascular events, but their net effects in people at low risk of vascular events remain uncertain. Methods This meta-analysis included individual participant data from 22 trials of statin versus control (n=134 537; mean LDL cholesterol difference 1·08 mmol/L; median follow-up 4·8 years) and five trials of more versus less statin (n=39 612; difference 0·51 mmol/L; 5·1 years). Major vascular events were major coronary events (ie, non-fatal myocardial infarction or coronary death), strokes, or coronary revascularisations. Participants were separated into five categories of baseline 5-year major vascular event risk on control therapy (no statin or low-intensity statin) (<5%, ≥5% to <10%, ≥10% to <20%, ≥20% to <30%, ≥30%); in each, the rate ratio (RR) per 1·0 mmol/L LDL cholesterol reduction was estimated. Findings Reduction of LDL cholesterol with a statin reduced the risk of major vascular events (RR 0·79, 95% CI 0·77–0·81, per 1·0 mmol/L reduction), largely irrespective of age, sex, baseline LDL cholesterol or previous vascular disease, and of vascular and all-cause mortality. The proportional reduction in major vascular events was at least as big in the two lowest risk categories as in the higher risk categories (RR per 1·0 mmol/L reduction from lowest to highest risk: 0·62 [99% CI 0·47–0·81], 0·69 [99% CI 0·60–0·79], 0·79 [99% CI 0·74–0·85], 0·81 [99% CI 0·77–0·86], and 0·79 [99% CI 0·74–0·84]; trend p=0·04), which reflected significant reductions in these two lowest risk categories in major coronary events (RR 0·57, 99% CI 0·36–0·89, p=0·0012, and 0·61, 99% CI 0·50–0·74, p<0·0001) and in coronary revascularisations (RR 0·52, 99% CI 0·35–0·75, and 0·63, 99% CI 0·51–0·79; both p<0·0001). For stroke, the reduction in risk in participants with 5-year risk of major vascular events lower than 10% (RR per 1·0 mmol/L LDL cholesterol reduction 0·76, 99% CI 0·61–0·95, p=0·0012) was also similar to that seen in higher risk categories (trend p=0·3). In participants without a history of vascular disease, statins reduced the risks of vascular (RR per 1·0 mmol/L LDL cholesterol reduction 0·85, 95% CI 0·77–0·95) and all-cause mortality (RR 0·91, 95% CI 0·85–0·97), and the proportional reductions were similar by baseline risk. There was no evidence that reduction of LDL cholesterol with a statin increased cancer incidence (RR per 1·0 mmol/L LDL cholesterol reduction 1·00, 95% CI 0·96–1·04), cancer mortality (RR 0·99, 95% CI 0·93–1·06), or other non-vascular mortality. Interpretation In individuals with 5-year risk of major vascular events lower than 10%, each 1 mmol/L reduction in LDL cholesterol produced an absolute reduction in major vascular events of about 11 per 1000 over 5 years. This benefit greatly exceeds any known hazards of statin therapy. Under present guidelines, such individuals would not typically be regarded as suitable for LDL-lowering statin therapy. The present report suggests, therefore, that these guidelines might need to be reconsidered. Funding British Heart Foundation; UK Medical Research Council; Cancer Research UK; European Community Biomed Programme; Australian National Health and Medical Research Council; National Heart Foundation, Australia.",
"title": "The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials"
},
{
"docid": "MED-2213",
"text": "CONTEXT: Alzheimer disease (AD) represents a major and increasing public health problem. If populations were identified with significantly lower or higher incidence rates of AD, the search for risk factors in the genesis of AD could be greatly enhanced. OBJECTIVE: To compare incidence rates of dementia and AD in 2 diverse, elderly community-dwelling populations. DESIGN: The Indianapolis-Ibadan Dementia Project, a longitudinal, prospective population-based study consisting of a baseline survey (1992-1993) and 2 subsequent follow-up waves after 2 years (1994-1995) and 5 years (1997-1998). Each wave followed a 2-stage design, with an in-home screening interview followed by a full diagnostic workup of a subsample of participants based on screening performance. SETTING AND PARTICIPANTS: A total of 2459 community-dwelling Yoruba residents of Ibadan, Nigeria, without dementia, and 2147 community-dwelling African American residents of Indianapolis, Ind, without dementia (all aged 65 years or older). The cohorts were followed up for a mean of 5.1 years and 4.7 years, respectively. MAIN OUTCOME MEASURES: Incident cases of dementia and AD in each of the 2 populations. RESULTS: The age-standardized annual incidence rates were significantly lower among Yoruba than among African Americans for dementia (Yoruba, 1.35% [95% confidence interval [CI], 1.13%-1.56%]; African Americans, 3.24% [95% CI, 2.11%-4.38%]) and for AD (Yoruba, 1.15% [95% CI, 0.96%-1.35%]; African Americans, 2.52% [95% CI, 1.40%-3.64%]). CONCLUSION: This is the first report of incidence rate differences for dementia and AD in studies of 2 populations from nonindustrialized and industrialized countries using identical methods and the same group of investigators in both sites. Further explorations of these population differences may identify potentially modifiable environmental or genetic factors to account for site differences in dementia and AD.",
"title": "Incidence of dementia and Alzheimer disease in 2 communities: Yoruba residing in Ibadan, Nigeria, and African Americans residing in Indianapolis, I..."
},
{
"docid": "MED-3796",
"text": "Lignans are a group of phytochemicals shown to have weakly estrogenic and antiestrogenic properties. Two specific lignans, enterodiol and enterolactone, are absorbed after formation in the intestinal tract from plant precursors particularly abundant in fiber-rich food and are excreted in the urine. We evaluated the effect of the ingestion of flax seed powder, known to produce high concentrations of urinary lignans, on the menstrual cycle in 18 normally cycling women, using a balanced randomized cross-over design. Each subject consumed her usual omnivorous, low fiber (control) diet for 3 cycles and her usual diet supplemented with flax seed for another 3 cycles. The second and third flax cycles were compared to the second and third control cycles. Three anovulatory cycles occurred during the 36 control cycles, compared to none during the 36 flax seed cycles. Compared to the ovulatory control cycles, the ovulatory flax cycles were consistently associated with longer luteal phase (LP) lengths (mean +/- SEM, 12.6 +/- 0.4 vs. 11.4 +/- 0.4 days; P = 0.002). There were no significant differences between flax and control cycles for concentrations of either estradiol or estrone during the early follicular phase, midfollicular phase, or LP. Although flax seed ingestion had no significant effect on LP progesterone concentrations, the LP progesterone/estradiol ratios were significantly higher during the flax cycles. Midfollicular phase testosterone concentrations were slightly higher during flax cycles. Flax seed ingestion had no effect on early follicular phase concentrations of DHEA-S, PRL, or sex hormone-binding globulin. Our data suggest a significant specific role for lignans in the relationship between diet and sex steroid action, and possibly between diet and the risk of breast and other hormonally dependent cancers.",
"title": "Effect of flax seed ingestion on the menstrual cycle."
},
{
"docid": "MED-4722",
"text": "BACKGROUND: There has been a resurgence of interest in the controversial relation between dietary protein and bone health. OBJECTIVE: This article reports on the first systematic review and meta-analysis of the relation between protein and bone health in healthy human adults. DESIGN: The MEDLINE (January 1966 to September 2007) and EMBASE (1974 to July 2008) databases were electronically searched for all relevant studies of healthy adults; studies of calcium excretion or calcium balance were excluded. RESULTS: In cross-sectional surveys, all pooled r values for the relation between protein intake and bone mineral density (BMD) or bone mineral content at the main clinically relevant sites were significant and positive; protein intake explained 1-2% of BMD. A meta-analysis of randomized placebo-controlled trials indicated a significant positive influence of all protein supplementation on lumbar spine BMD but showed no association with relative risk of hip fractures. No significant effects were identified for soy protein or milk basic protein on lumbar spine BMD. CONCLUSIONS: A small positive effect of protein supplementation on lumbar spine BMD in randomized placebo-controlled trials supports the positive association between protein intake and bone health found in cross-sectional surveys. However, these results were not supported by cohort study findings for hip fracture risk. Any effects found were small and had 95% CIs that were close to zero. Therefore, there is a small benefit of protein on bone health, but the benefit may not necessarily translate into reduced fracture risk in the long term.",
"title": "Dietary protein and bone health: a systematic review and meta-analysis."
},
{
"docid": "MED-3272",
"text": "Objective Early detection and early treatment are of vital importance to the successful treatment of various cancers. The development of a novel screening method that is as economical and non-invasive as the faecal occult blood test (FOBT) for early detection of colorectal cancer (CRC) is needed. A study was undertaken using canine scent detection to determine whether odour material can become an effective tool in CRC screening. Design Exhaled breath and watery stool samples were obtained from patients with CRC and from healthy controls prior to colonoscopy. Each test group consisted of one sample from a patient with CRC and four control samples from volunteers without cancer. These five samples were randomly and separately placed into five boxes. A Labrador retriever specially trained in scent detection of cancer and a handler cooperated in the tests. The dog first smelled a standard breath sample from a patient with CRC, then smelled each sample station and sat down in front of the station in which a cancer scent was detected. Results 33 and 37 groups of breath and watery stool samples, respectively, were tested. Among patients with CRC and controls, the sensitivity of canine scent detection of breath samples compared with conventional diagnosis by colonoscopy was 0.91 and the specificity was 0.99. The sensitivity of canine scent detection of stool samples was 0.97 and the specificity was 0.99. The accuracy of canine scent detection was high even for early cancer. Canine scent detection was not confounded by current smoking, benign colorectal disease or inflammatory disease. Conclusions This study shows that a specific cancer scent does indeed exist and that cancer-specific chemical compounds may be circulating throughout the body. These odour materials may become effective tools in CRC screening. In the future, studies designed to identify cancer-specific volatile organic compounds will be important for the development of new methods for early detection of CRC.",
"title": "Colorectal cancer screening with odour material by canine scent detection"
},
{
"docid": "MED-2114",
"text": "Acne in adolescents of developed countries is an epidemic skin disease and has currently been linked to the Western diet (WD). It is the intention of this viewpoint to discuss the possible impact of WD-mediated nutrient signalling in the pathogenesis of acne. High glycaemic load and dairy protein consumption both increase insulin/insulin-like growth factor-1 (IGF-1) signalling (IIS) that is superimposed on elevated IGF-1 signalling of puberty. The cell's nutritional status is primarily sensed by the forkhead box transcription factor O1 (FoxO1) and the serine/threonine kinase mammalian target of rapamycin complex 1 (mTORC1). Increased IIS extrudes FoxO1 into the cytoplasm, whereas nuclear FoxO1 suppresses hepatic IGF-1 synthesis and thus impairs somatic growth. FoxO1 attenuates androgen signalling, interacts with regulatory proteins important for sebaceous lipogenesis, regulates the activity of innate and adaptive immunity, antagonizes oxidative stress and most importantly functions as a rheostat of mTORC1, the master regulator of cell growth, proliferation and metabolic homoeostasis. Thus, FoxO1 links nutrient availability to mTORC1-driven processes: increased protein and lipid synthesis, cell proliferation, cell differentiation including hyperproliferation of acroinfundibular keratinocytes, sebaceous gland hyperplasia, increased sebaceous lipogenesis, insulin resistance and increased body mass index. Enhanced androgen, TNF-α and IGF-1 signalling due to genetic polymorphisms promoting the risk of acne all converge in mTORC1 activation, which is further enhanced by nutrient signalling of WD. Deeper insights into the molecular interplay of FoxO1/mTORC1-mediated nutrient signalling are thus of critical importance to understand the impact of WD on the promotion of epidemic acne and more serious mTORC1-driven diseases of civilization.",
"title": "Potential role of FoxO1 and mTORC1 in the pathogenesis of Western diet-induced acne"
},
{
"docid": "MED-2116",
"text": "Over the past 10 years, the increase in comprehension of the mechanisms behind acne has been truly exponential. Starting with the ethnological work of Cordain, accelerated by the epidemiological work of Adebamowo, supported by the clinical trials of Smith and Mann, Kwon, DiLandro and others, the interface of diet and acne is coming into focus. Melnik now presents an exceptional pair of papers that illustrate for dermatologists what translational research is all about. The Western diet, the role of dairy, FoxO1 and mTORC1, the interplay of agonists and antagonists, therapeutics present and future – the jigsaw puzzle is coming together.",
"title": "Turning acne on/off via mTORC1"
},
{
"docid": "MED-2972",
"text": "BACKGROUND: Elevated levels of lipids, such as total cholesterol (TC), low-density lipoprotein cholesterol (LDL), and triglycerides (TG), are widely recognized as risk factors for cardiovascular disease (CVD). Oxidized LDL (OxLDL) is an emerging risk factor considered relevant in oxidative stress and endothelial dysfunction, which is implicated in the progression of CVD. Consumption of a diet rich in polyphenols may be cardioprotective through its impact on oxidative stress and protecting LDL from oxidation. OBJECTIVES: This study was designed to test the ability of strawberry phenolic compounds to mitigate the postprandial effects of a high-fat meal on OxLDL as well as investigate the effects of phenolic compounds on lipid metabolism. METHODS: Twenty-four hyperlipidemic men and women (14 women, 10 men; mean age 50.9 +/- SD 15 years) were recruited to participate in this randomized, single-blind, placebo-controlled, 12-wk crossover trial. After a 10-day run-in period, subjects consumed either an active strawberry beverage (Str; containing 10 g freeze-dried fruit) or a placebo (Pbo) beverage matched in energy and macronutrient composition for 6 weeks. Twice before randomization and once at the 6-week crossover point, subjects received either Str or Pbo with a high-fat challenge meal (HFM). TC, LDL, high-density lipoprotein cholesterol, TG, and OxLDL were measured at defined intervals for 6 h before and after HFM challenge. Fasting concentrations of blood variables at 0, 6, and 12 weeks were compared to assess chronic intake of Str or Pbo. RESULTS: After the HFM during the run-in period, TG and OxLDL were lower after Str than Pbo (p = 0.005, p = 0.01, and p = 0.0008, respectively). HFM responses after 6 weeks of Str versus Pbo resulted in decreased lipid levels and a sex by treatment interaction for OxLDL (p = < 0.0001, and p = 0.0002). CONCLUSION: The present results support a role for strawberry in mitigating fed-state oxidative stressors that may contribute to atherogenesis.",
"title": "Strawberry modulates LDL oxidation and postprandial lipemia in response to high-fat meal in overweight hyperlipidemic men and women."
},
{
"docid": "MED-3699",
"text": "BACKGROUND: In 2007 the World Cancer Research Fund (WCRF) and the American Institute of Cancer Research (AICR) issued 8 recommendations (plus 2 special recommendations) on diet, physical activity, and weight management for cancer prevention on the basis of the most comprehensive collection of available evidence. OBJECTIVE: We aimed to investigate whether concordance with the WCRF/AICR recommendations was related to cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. DESIGN: The present study included 386,355 EPIC participants from 9 European countries. At recruitment, dietary, anthropometric, and lifestyle information was collected. A score was constructed based on the WCRF/AICR recommendations on weight management, physical activity, foods and drinks that promote weight gain, plant foods, animal foods, alcoholic drinks, and breastfeeding for women; the score range was 0-6 for men and 0-7 for women. Higher scores indicated greater concordance with WCRF/AICR recommendations. The association between the score and cancer risk was estimated by using multivariable Cox regression models. RESULTS: Concordance with the score was significantly associated with decreased risk of cancer. A 1-point increment in the score was associated with a risk reduction of 5% (95% CI: 3%, 7%) for total cancer, 12% (95% CI: 9%, 16%) for colorectal cancer, and 16% (95% CI: 9%, 22%) for stomach cancer. Significant associations were also observed for cancers of the breast, endometrium, lung, kidney, upper aerodigestive tract, liver, and esophagus but not for prostate, ovarian, pancreatic, and bladder cancers. CONCLUSION: Adherence to the WCRF/AICR recommendations for cancer prevention may lower the risk of developing most types of cancer.",
"title": "Is concordance with World Cancer Research Fund/American Institute for Cancer Research guidelines for cancer prevention related to subsequent risk o..."
},
{
"docid": "MED-2288",
"text": "In recent years there has been considerable interest in the benefits of high-protein diets. This study determined current usual intake of protein in America. Using the most recent data from the National Health and Nutrition Examination Survey, 2003-2004, usual protein intake for Americans aged 2+ years was estimated. Usual protein intake was calculated on a grams per day, grams per kilogram ideal body weight, and a percentage of calories basis. Protein intake averaged 56 +/- 14 g/d in young children, increased to a high of approximately 91 +/- 22 g/d in adults aged 19-30 y, and decreased to approximately 66 +/- 17 g/d in the elderly. The percentage of the male population who consumed less than the estimated average requirement was very low. Our estimates indicated that 7.7% of adolescent females and 7.2-8.6% of older adult women reported consuming protein levels below their estimated average requirement. The median intake of protein on a percentage of calories basis ranged from 13.4% in children aged 4-8 y to 16.0% in men aged 51-70 y. Even the 95th percentile of protein intake did not approach the highest acceptable macronutrient distribution range of 35% for an age/sex group. The highest 95th percentile of protein intake was 20.8% of calories in men aged 51-70 y. Given the demonstrated benefits of higher protein intake on weight management, sarcopenia, and other physiologic functions, efforts should be undertaken to ensure that Americans consume the recommended amount of protein (17-21% of calories as expected from MyPyramid food patterns).",
"title": "Current protein intake in America: analysis of the National Health and Nutrition Examination Survey, 2003-2004."
},
{
"docid": "MED-1813",
"text": "PURPOSE: Pancreatic cancer is almost always lethal, and the only U.S. Food and Drug Administration-approved therapies for it, gemcitabine and erlotinib, produce objective responses in <10% of patients. We evaluated the clinical biological effects of curcumin (diferuloylmethane), a plant-derived dietary ingredient with potent nuclear factor-kappaB (NF-kappaB) and tumor inhibitory properties, against advanced pancreatic cancer. EXPERIMENTAL DESIGN: Patients received 8 g curcumin by mouth daily until disease progression, with restaging every 2 months. Serum cytokine levels for interleukin (IL)-6, IL-8, IL-10, and IL-1 receptor antagonists and peripheral blood mononuclear cell expression of NF-kappaB and cyclooxygenase-2 were monitored. RESULTS: Twenty-five patients were enrolled, with 21 evaluable for response. Circulating curcumin was detectable as drug in glucuronide and sulfate conjugate forms, albeit at low steady-state levels, suggesting poor oral bioavailability. Two patients showed clinical biological activity. One had ongoing stable disease for >18 months; interestingly, one additional patient had a brief, but marked, tumor regression (73%) accompanied by significant increases (4- to 35-fold) in serum cytokine levels (IL-6, IL-8, IL-10, and IL-1 receptor antagonists). No toxicities were observed. Curcumin down-regulated expression of NF-kappaB, cyclooxygenase-2, and phosphorylated signal transducer and activator of transcription 3 in peripheral blood mononuclear cells from patients (most of whom had baseline levels considerably higher than those found in healthy volunteers). Whereas there was considerable interpatient variation in plasma curcumin levels, drug levels peaked at 22 to 41 ng/mL and remained relatively constant over the first 4 weeks. CONCLUSIONS: Oral curcumin is well tolerated and, despite its limited absorption, has biological activity in some patients with pancreatic cancer.",
"title": "Phase II trial of curcumin in patients with advanced pancreatic cancer."
},
{
"docid": "MED-2123",
"text": "Milk has been recognized to represent a functionally active nutrient system promoting neonatal growth of mammals. Cell growth is regulated by the nutrient-sensitive kinase mechanistic target of rapamycin complex 1 (mTORC1). There is still a lack of information on the mechanisms of mTORC1 up-regulation by milk consumption. This review presents milk as a materno-neonatal relay system functioning by transfer of preferential amino acids, which increase plasma levels of glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), insulin, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) for mTORC1 activation. Importantly, milk exosomes, which regularly contain microRNA-21, most likely represent a genetic transfection system enhancing mTORC1-driven metabolic processes. Whereas human breast milk is the ideal food for infants allowing appropriate postnatal growth and species-specific metabolic programming, persistent high milk signaling during adolescence and adulthood by continued cow´s milk consumption may promote mTORC1-driven diseases of civilization.",
"title": "Milk is not just food but most likely a genetic transfection system activating mTORC1 signaling for postnatal growth"
},
{
"docid": "MED-2120",
"text": "In a recent study, prostatectomy specimens from which Propionibacterium acnes was cultured were more likely to have inflammation than culture-negative specimens or specimens positive for other bacteria, leading the authors to hypothesize that P. acnes-mediated inflammation may contribute to prostate carcinogenesis. To indirectly explore associations between P. acnes and prostate cancer, we investigated severe acne, as measured by tetracycline use for four or more years, in relation to incident prostate cancer in the Health Professionals Follow-up Study. On the 1992 follow-up questionnaire, participants were asked whether they had ever used “tetracycline for at least two months at a time (e.g., for acne or other reason)” and their duration of use. Prostate cancer diagnoses were ascertained on each subsequent biennial questionnaire and confirmed by medical record review. Between 1992 and 2002, 2,147 cases of prostate cancer were reported among 34,629 eligible participants. Men who used tetracycline for four or more years had a significantly higher risk of prostate cancer (16 cases, 1,569 person-years) than men who did not use tetracycline (2,071 cases, 304,822 person-years, multivariable-adjusted RR=1.70, 95% CI:1.03–2.80). Although intriguing, this finding should be viewed cautiously because of the small number of exposed cases, indirect assessment of severe acne, and complex etiology of acne, which is not limited to P. acnes infection. Therefore, additional biologic and epidemiologic studies are necessary to determine and elucidate the possible role of P. acnes infection in prostate carcinogenesis.",
"title": "ACNE AND RISK OF PROSTATE CANCER"
},
{
"docid": "MED-5072",
"text": "Antioxidant-rich diets are associated with reduced asthma prevalence. However, direct evidence that altering intake of antioxidant-rich foods affects asthma is lacking. The objective was to investigate changes in asthma and airway inflammation resulting from a low antioxidant diet and subsequent use of lycopene-rich treatments. Asthmatic adults (n=32) consumed a low antioxidant diet for 10 days, then commenced a randomized, cross-over trial involving 3 x 7 day treatment arms (placebo, tomato extract (45 mg lycopene/day) and tomato juice (45 mg lycopene/day)). With consumption of a low antioxidant diet, plasma carotenoid concentrations decreased, Asthma Control Score worsened, %FEV(1) and %FVC decreased and %sputum neutrophils increased. Treatment with both tomato juice and extract reduced airway neutrophil influx. Treatment with tomato extract also reduced sputum neutrophil elastase activity. In conclusion, dietary antioxidant consumption modifies clinical asthma outcomes. Changing dietary antioxidant intake may be contributing to rising asthma prevalence. Lycopene-rich supplements should be further investigated as a therapeutic intervention.",
"title": "Lycopene-rich treatments modify noneosinophilic airway inflammation in asthma: proof of concept."
},
{
"docid": "MED-1658",
"text": "PURPOSE: To evaluate the correlation of the diffusion values in lumbar intervertebral disks with lumbar artery status and the degree of disk degeneration. MATERIALS AND METHODS: Sagittal T2-weighted images of the lumbar spine were obtained in 37 asymptomatic volunteers aged 22-68 years. The apparent diffusion coefficient (ADC) of 98 lumbar intervertebral disks was determined, and two-dimensional time-of-flight magnetic resonance angiography was performed on the corresponding 98 lumbar artery pairs (total arteries = 196). The degree of disk degeneration and the status of lumbar arteries were evaluated independently by two radiologists. ADC calculations were performed on the basis of the average signal intensities of the selected region of interest in lumbar disks. The association between ADC values of disks, the disk degeneration, and the status of lumbar arteries of the same level were analyzed with analysis of covariance, and pairwise analysis between groups (Scheffé post hoc multiple comparison) was performed with statistical software. P values less than .01 were considered significant. RESULTS: The lumbar arterial status correlated strongly with the diffusion values of intervertebral disks, and the ADC values decreased with higher degrees of arterial narrowing. The correlation between disk degeneration and diffusion was not significant. Eight severely degenerated disks with normal lumbar artery status and diffusion values were found. CONCLUSION: Impaired flow in lumbar arteries is significantly associated with decreased diffusion in lumbar disks and may play an important role in disk degeneration.",
"title": "Correlation of diffusion in lumbar intervertebral disks with occlusion of lumbar arteries: a study in adult volunteers."
},
{
"docid": "MED-1205",
"text": "Plaque disruption (PD) causes most acute cardiovascular events. Although cholesterol crystals (CCs) have been observed in plaques, their role in PD was unknown. However, cholesterol expands with crystallization tearing and perforating fibrous tissues. This study tested the hypothesis that CCs can damage plaques and intima, triggering PD, as observed in tissues prepared without ethanol solvents that dissolve CCs. Coronary arteries of patients who died of acute coronary syndrome (n = 19) and non-acute coronary syndrome causes (n = 12) and carotid plaques from patients with (n = 51) and without (n = 19) neurologic symptoms were studied. Samples were examined for CCs perforating the intima using light and scanning electron microscopy (SEM) with ethanol or vacuum dehydration. In addition, fresh unfixed carotid plaques were examined at 37 degrees C using confocal microscopy. Crystal content using SEM was scored from 0 to +3. SEM using vacuum dehydration had significantly higher crystal content compared with SEM using ethanol dehydration (+2.5 +/- 0.53 vs +0.25 +/- 0.46; p <0.0003), with enhanced detection of CC perforations. The presence of CCs using SEM and confocal microscopy was similar, suggesting that CC perforation can occur in vivo at 37 degrees C. All patients with acute coronary syndrome had perforating CCs, but none was present in patients without acute coronary syndrome (p = 0.0001). For all plaques, there were strong associations of CCs with PD, thrombus, symptoms (p <0.0001), and plaque size (p <0.02). Crystal content was an independent predictor of thrombus and symptoms. In conclusion, by avoiding ethanol in tissue preparation, CCs perforating the intima were shown to be associated with PD. Crystal content was significantly associated with clinical events, suggesting that cholesterol crystallization may have a role in PD.",
"title": "Effect of cholesterol crystals on plaques and intima in arteries of patients with acute coronary and cerebrovascular syndromes."
},
{
"docid": "MED-3111",
"text": "The intraepithelial lymphocytes (IELs) that reside within the epithelium of the intestine form one of the main branches of the immune system. As IELs are located at this critical interface between the core of the body and the outside environment, they must balance protective immunity with an ability to safeguard the integrity of the epithelial barrier: failure to do so would compromise homeostasis of the organism. In this Review, we address how the unique development and functions of intestinal IELs allow them to achieve this balance.",
"title": "The light and dark sides of intestinal intraepithelial lymphocytes"
},
{
"docid": "MED-3107",
"text": "The intestinal intraepithelial lymphocytes (IELs) are mostly T cells dispersed as single cells within the epithelial cell layer that surrounds the intestinal lumen. IELs are, therefore, strategically located at the interface between the antigen-rich outside world and the sterile core of the body. The intestine of higher vertebrates has further evolved to harbor numerous commensal bacteria that carry out important functions for the host, and while defensive immunity can effectively protect against the invasion of pathogens, similar immune reactions against food-derived antigens or harmless colonizing bacteria can result in unnecessary and sometimes damaging immune responses. Probably as a result of this unique dilemma imposed by the gut environment, multiple subsets of IEL have differentiated, which all display characteristics of 'activated yet resting' immune cells. Despite this common feature, IELs are heterogeneous with regard to their phenotype, ontogeny, and function. In this review, we discuss the different subtypes of IELs and highlight the distinct pathways they took that led to their unique differentiation into highly specialized effector memory T cells, which provide the most effective immune protection yet in a strictly regulated fashion to preserve the integrity and vital functions of the intestinal mucosal epithelium.",
"title": "IELs: enforcing law and order in the court of the intestinal epithelium."
},
{
"docid": "MED-4522",
"text": "BACKGROUND AND AIMS: Oxidative stress has been advocated as a major cause for cardiovascular disease (CVD), and low plasma antioxidant concentrations are associated with endothelial dysfunction, the first step towards atherosclerosis. However, although the antioxidant content in fruits and vegetables may explain at least in part their protective effect against CVD, supplementation with antioxidant vitamins fails to improve endothelial function and reduce CVD risk. The aim of this study was to investigate the impact of a diet rich in antioxidants on endothelial function measured by flow-mediated dilatation (FMD) in volunteers at low cardiovascular risk. METHODS AND RESULTS: In a crossover trial, 24 subjects (13 women, mean age 61 ± 3 years), received, in a randomised order, a 14-day high (HT) and a 14-day low (LT) antioxidant diets, with a 2-week wash-out (WO) in between. Both diets were comparable in daily portions of fruits and vegetables, and in alcohol, fibre and macronutrient intake, but differed in their total antioxidant capacity. Before and after each diet, anthropometrics, blood pressure, fasting plasma glucose, lipid profile, hepatic enzymes, circulating antioxidant concentrations, high sensitivity C-reactive protein (hs-CRP) and FMD were assessed. FMD increased significantly during the HT diet compared to the LT (p < 0.000). FMD values were 2.3% higher after HT compared with LT (p < 0.001) after adjustment for age, gender and diet order. α-tocopherol increased significantly (p < 0.05) and hs-CRP and of γ-glutamyltranspeptidase decreased significantly (p < 0.05 and p < 0.01, respectively) during the HT diet, compared with the LT diet. CONCLUSIONS: A short-term HT diet improves endothelial function in volunteers at low cardiovascular risk, which may further reduce their risk of CVD. Copyright © 2010 Elsevier B.V. All rights reserved.",
"title": "Food selection based on high total antioxidant capacity improves endothelial function in a low cardiovascular risk population."
},
{
"docid": "MED-3877",
"text": "OBJECTIVES: Dietary factors may influence the prostate and have an impact on prostatic growth and disease. A small number of studies have suggested that flaxseed-supplemented, fat-restricted diets may thwart prostate cancer growth in both animals and humans. Unknown, however, is the potential effect of such a diet on benign prostatic epithelium. METHODS: We undertook a pilot study to explore whether a flaxseed-supplemented, fat-restricted diet affects the proliferation rates in benign epithelium. We also explored the effects on circulating levels of prostate-specific antigen (PSA), total testosterone, and cholesterol. Fifteen men who were scheduled to undergo repeat prostate biopsy were instructed to follow a low-fat (less than 20% kcal), flaxseed-supplemented (30 g/day) diet and were provided with a supply of flaxseed to last throughout the 6-month intervention period. The PSA, total testosterone, and cholesterol levels were determined at baseline and at 6 months of follow-up. Reports from the original and repeat biopsies were compared, and proliferation (MIB-1) rates were quantified in the benign prostatic epithelium. RESULTS: Statistically significant decreases in PSA (8.47 +/- 3.82 to 5.72 +/- 3.16 ng/mL; P = 0.0002) and cholesterol (241.1 +/- 30.8 to 213.3 +/- 51.2 mg/dL; P = 0.012) were observed. No statistically significant change was seen in total testosterone (434.5 +/- 143.6 to 428.3 +/- 92.5 ng/dL). Although 6-month repeat biopsies were not performed in 2 cases because of PSA normalization, of the 13 men who underwent repeat biopsy, the proliferation rates in the benign epithelium decreased significantly from 0.022 +/- 0.027 at baseline to 0.007 +/- 0.014 at 6 months of follow-up (P = 0.0168). CONCLUSIONS: These pilot data suggest that a flaxseed-supplemented, fat-restricted diet may affect the biology of the prostate and associated biomarkers. A randomized controlled trial is needed to determine whether flaxseed supplementation, a low-fat diet, or a combination of the two regimens may be of use in controlling overall prostatic growth.",
"title": "Pilot study to explore effects of low-fat, flaxseed-supplemented diet on proliferation of benign prostatic epithelium and prostate-specific antigen."
},
{
"docid": "MED-2997",
"text": "If disease patterns emerge which show that certain diseases can be related, this is a valuable pointer to a common cause. This article traces the principle of interpreting disease relationships, illustrated by several common conditions of western civilization, for which the common cause is postulated as being removal of fiber from the diet.",
"title": "The Etiological Significance of Related Diseases"
},
{
"docid": "MED-3448",
"text": "Iodine is a suspected risk factor for thyroid cancer. Seaweed accounts for about 80% of Japanese people's iodine intake. We examined the association between seaweed consumption and the risk of thyroid cancer in Japanese women. Women participating in the Japan Public Health Center-based Prospective Study (n=52 679; age: 40-69 years) were followed up for a mean of 14.5 years; 134 new thyroid cancer cases, including 113 papillary carcinoma cases, were identified. Seaweed consumption was assessed using a food-frequency questionnaire and divided into three categories: 2 days/week or less (reference); 3-4 days/week; and almost daily. The Cox proportional hazards model was applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Seaweed consumption was clearly associated with an increased risk of papillary carcinoma (HR for almost daily consumption compared with 2 days/week or less=1.71; 95% CI: 1.01-2.90; trend P=0.04). After stratification for menopausal status, an increased risk was observed in postmenopausal women (papillary carcinoma HR for almost daily consumption compared with 2 days/week or less=3.81, 95% CI: 1.67-8.68; trend P<0.01), but not in premenopausal women (HR=0.91, 95% CI: 0.44-1.91; trend P=0.76). This study identified a positive association between seaweed consumption and the risk of thyroid cancer (especially for papillary carcinoma) in postmenopausal women.",
"title": "Seaweed consumption and the risk of thyroid cancer in women: the Japan Public Health Center-based Prospective Study."
},
{
"docid": "MED-2805",
"text": "Obesity is a significant risk factor for developing osteoarthritis in weight-bearing and non-weight-bearing joints. Although the pathogenesis of obesity-associated osteoarthritis is not completely understood, recent studies indicate that pro-inflammatory metabolic factors contribute to an increase in osteoarthritis risk. Adipose tissue, and in particular infrapatellar fat, is a local source of pro-inflammatory mediators that are increased with obesity and have been shown to increase cartilage degradation in cell and tissue culture models. One adipokine in particular, leptin, may be a critical mediator of obesity-associated osteoarthritis via synergistic actions with other inflammatory cytokines. Biomechanical factors may also increase the risk of osteoarthritis by activating cellular inflammation and promoting oxidative stress. However, some types of biomechanical stimulation, such as physiologic cyclic loading, inhibit inflammation and protect against cartilage degradation. A high percentage of obese individuals with knee osteoarthritis are sedentary, suggesting that a lack of physical activity may increase the susceptibility to inflammation. A more comprehensive approach to understanding how obesity alters daily biomechanical exposures within joint tissues may provide new insight into the protective and damaging effects of biomechanical factors on inflammation in osteoarthritis.",
"title": "Pathobiology of obesity and osteoarthritis: integrating biomechanics and inflammation"
},
{
"docid": "MED-3106",
"text": "PURPOSE OF REVIEW: The aryl hydrocarbon receptor (AhR), a transcription factor activated by a large number of environmental agents, modulates the activity of immune and nonimmune cells in the gut, and may represent an important link between the environment and the immune perturbations which underlie the pathogenesis of inflammatory bowel disease. This review will summarize the current knowledge of the role of AhR in regulation of intestinal immune homeostasis and inflammation. RECENT FINDINGS: Activation of AhR by dietary ligands is necessary for the maintenance or expansion of innate immune cells in the gut, such as intraepithelial lymphocytes (IELs) and interleukin (IL)-22-producing lymphoid cells (ILC22). AhR-deficient mice lack IELs, have reduced number of ILC22 cells, and are more susceptible to bacterial infections and experimental colitis. In animal models, AhR activators inhibit proinflammatory cytokine synthesis and attenuate colitis by a pathway that involves IL-22. Analysis of AhR in the human gut reveals that intestinal T cells and natural killer cells isolated from Crohn's disease patients express low levels of AhR and respond to AhR ligands by downregulating inflammatory cytokines and upregulating IL-22. SUMMARY: These novel findings may help explain how environmental factors may regulate mucosal immune responses.",
"title": "The aryl hydrocarbon receptor in inflammatory bowel disease: linking the environment to disease pathogenesis."
},
{
"docid": "MED-1404",
"text": "OBJECTIVE: The purpose of this work was to meta-analyze prospective studies that have evaluated the effect of a Mediterranean diet on the development of type 2 diabetes. MATERIALS/METHODS: PubMed, Embase and the Cochrane Central Register of Controlled Trials databases were searched up to 20 November 2013. English language publications were allocated; 17 original research studies (1 clinical trial, 9 prospective and 7 cross-sectional) were identified. Primary analyses were limited to prospective studies and clinical trials, yielding to a sample of 136,846 participants. A systematic review and a random effects meta-analysis were conducted. RESULTS: Higher adherence to the Mediterranean diet was associated with 23% reduced risk of developing type 2 diabetes (combined relative risk for upper versus lowest available centile: 0.77; 95% CI: 0.66, 0.89). Subgroup analyses based on region, health status of participants and number of confounders controlling for, showed similar results. Limitations include variations in Mediterranean diet adherence assessment tools, confounders' adjustment, duration of follow up and number of events with diabetes. CONCLUSIONS: The presented results are of major public health importance, since no consensus exists concerning the best anti-diabetic diet. Mediterranean diet could, if appropriately adjusted to reflect local food availability and individual's needs, constitute a beneficial nutritional choice for the primary prevention of diabetes. Copyright © 2014 Elsevier Inc. All rights reserved.",
"title": "The effect of Mediterranean diet on the development of type 2 diabetes mellitus: a meta-analysis of 10 prospective studies and 136,846 participants."
},
{
"docid": "MED-4896",
"text": "BACKGROUND: In westernized societies, acne vulgaris is a nearly universal skin disease afflicting 79% to 95% of the adolescent population. In men and women older than 25 years, 40% to 54% have some degree of facial acne, and clinical facial acne persists into middle age in 12% of women and 3% of men. Epidemiological evidence suggests that acne incidence rates are considerably lower in nonwesternized societies. Herein we report the prevalence of acne in 2 nonwesternized populations: the Kitavan Islanders of Papua New Guinea and the Aché hunter-gatherers of Paraguay. Additionally, we analyze how elements in nonwesternized environments may influence the development of acne. OBSERVATIONS: Of 1200 Kitavan subjects examined (including 300 aged 15-25 years), no case of acne (grade 1 with multiple comedones or grades 2-4) was observed. Of 115 Aché subjects examined (including 15 aged 15-25 years) over 843 days, no case of active acne (grades 1-4) was observed. CONCLUSIONS: The astonishing difference in acne incidence rates between nonwesternized and fully modernized societies cannot be solely attributed to genetic differences among populations but likely results from differing environmental factors. Identification of these factors may be useful in the treatment of acne in Western populations.",
"title": "Acne vulgaris: a disease of Western civilization."
},
{
"docid": "MED-2124",
"text": "Acne appears to represent a visible indicator disease of over-activated mTORC1 signalling, an unfavour-able metabolic deviation on the road to serious common Western diseases of civilisation associated with increased body mass index and insulin resistance. Exaggerated mTORC1 signalling by Western diet explains the association of acne with increased body mass index, insulin resistance, and early onset of menarche. Both, a high glycaemic load and increased consumption of milk and milk products, staples of Western diet, aggravate mammalian target of rapamycin complex 1 signalling. This review of the literature summarises present evidence for an association between acne, increased body mass index, insulin resistance and Western diet. By dietary intervention with a Palaeolithic-type diet, the dermatologist has the chance to attenuate patients' increased mTORC1 signalling by reducing glycaemic load and milk consumption, which may not only improve acne but may delay the march to more serious mTORC1-driven diseases of civilisation.",
"title": "Acne: risk indicator for increased body mass index and insulin resistance."
},
{
"docid": "MED-4496",
"text": "BACKGROUND: Many constituents of fruits and vegetables may reduce the risk for coronary heart disease, but data on the relationship between fruit and vegetable consumption and risk for coronary heart disease are sparse. OBJECTIVE: To evaluate the association of fruit and vegetable consumption with risk for coronary heart disease. DESIGN: Prospective cohort study. SETTING: The Nurses' Health Study and the Health Professionals' Follow-Up Study. PARTICIPANTS: 84 251 women 34 to 59 years of age who were followed for 14 years and 42 148 men 40 to 75 years who were followed for 8 years. All were free of diagnosed cardiovascular disease, cancer, and diabetes at baseline. MEASUREMENTS: The main outcome measure was incidence of nonfatal myocardial infarction or fatal coronary heart disease (1127 cases in women and 1063 cases in men). Diet was assessed by using food-frequency questionnaires. RESULTS: After adjustment for standard cardiovascular risk factors, persons in the highest quintile of fruit and vegetable intake had a relative risk for coronary heart disease of 0.80 (95% CI, 0.69 to 0.93) compared with those in the lowest quintile of intake. Each 1-serving/d increase in intake of fruits or vegetables was associated with a 4% lower risk for coronary heart disease (relative risk, 0.96 [CI, 0.94 to 0.99]; P = 0.01, test for trend). Green leafy vegetables (relative risk with 1-serving/d increase, 0.77 [CI, 0.64 to 0.93]), and vitamin C-rich fruits and vegetables (relative risk with 1-serving/d increase, 0.94 [CI, 0.88 to 0.99]) contributed most to the apparent protective effect of total fruit and vegetable intake. CONCLUSIONS: Consumption of fruits and vegetables, particularly green leafy vegetables and vitamin C-rich fruits and vegetables, appears to have a protective effect against coronary heart disease.",
"title": "The effect of fruit and vegetable intake on risk for coronary heart disease."
},
{
"docid": "MED-1862",
"text": "BACKGROUND: The main 6-month results from the PREMIER trial showed that comprehensive behavioral intervention programs improve lifestyle behaviors and lower blood pressure. OBJECTIVE: To compare the 18-month effects of 2 multicomponent behavioral interventions versus advice only on hypertension status, lifestyle changes, and blood pressure. DESIGN: Multicenter, 3-arm, randomized trial conducted from January 2000 through November 2002. SETTING: 4 clinical centers and a coordinating center. PATIENTS: 810 adult volunteers with prehypertension or stage 1 hypertension (systolic blood pressure, 120 to 159 mm Hg; diastolic blood pressure, 80 to 95 mm Hg). INTERVENTIONS: A multicomponent behavioral intervention that implemented long-established recommendations (\"established\"); a multicomponent behavioral intervention that implemented the established recommendations plus the Dietary Approaches to Stop Hypertension (DASH) diet (\"established plus DASH\"); and advice only. MEASUREMENTS: Lifestyle variables and blood pressure status. Follow-up for blood pressure measurement at 18 months was 94%. RESULTS: Compared with advice only, both behavioral interventions statistically significantly reduced weight, fat intake, and sodium intake. The established plus DASH intervention also statistically significantly increased fruit, vegetable, dairy, fiber, and mineral intakes. Relative to the advice only group, the odds ratios for hypertension at 18 months were 0.83 (95% CI, 0.67 to 1.04) for the established group and 0.77 (CI, 0.62 to 0.97) for the established plus DASH group. Although reductions in absolute blood pressure at 18 months were greater for participants in the established and the established plus DASH groups than for the advice only group, the differences were not statistically significant. LIMITATIONS: The exclusion criteria and the volunteer nature of this cohort may limit generalizability. Although blood pressure is a well-accepted risk factor for cardiovascular disease, the authors were not able to assess intervention effects on clinical cardiovascular events in this limited time and with this sample size. CONCLUSIONS: Over 18 months, persons with prehypertension and stage 1 hypertension can sustain multiple lifestyle modifications that improve control of blood pressure and could reduce the risk for chronic disease.",
"title": "Effects of comprehensive lifestyle modification on diet, weight, physical fitness, and blood pressure control: 18-month results of a randomized trial."
},
{
"docid": "MED-4640",
"text": "BACKGROUND: The gut and immune system form a complex integrated structure that has evolved to provide effective digestion and defence against ingested toxins and pathogenic bacteria. However, great variation exists in what is considered normal healthy gut and immune function. Thus, whilst it is possible to measure many aspects of digestion and immunity, it is more difficult to interpret the benefits to individuals of variation within what is considered to be a normal range. Nevertheless, it is important to set standards for optimal function for use both by the consumer, industry and those concerned with the public health. The digestive tract is most frequently the object of functional and health claims and a large market already exists for gut-functional foods worldwide. AIM: To define normal function of the gut and immune system and describe available methods of measuring it. RESULTS: We have defined normal bowel habit and transit time, identified their role as risk factors for disease and how they may be measured. Similarly, we have tried to define what is a healthy gut flora in terms of the dominant genera and their metabolism and listed the many, varied and novel methods for determining these parameters. It has proved less easy to provide boundaries for what constitutes optimal or improved gastric emptying, gut motility, nutrient and water absorption and the function of organs such as the liver, gallbladder and pancreas. The many tests of these functions are described. We have discussed gastrointestinal well being. Sensations arising from the gut can be both pleasant and unpleasant. However, the characteristics of well being are ill defined and merge imperceptibly from acceptable to unacceptable, a state that is subjective. Nevertheless, we feel this is an important area for future work and method development. The immune system is even more difficult to make quantitative judgements about. When it is defective, then clinical problems ensure, but this is an uncommon state. The innate and adaptive immune systems work synergistically together and comprise many cellular and humoral factors. The adaptive system is extremely sophisticated and between the two arms of immunity there is great redundancy, which provides robust defences. New aspects of immune function are discovered regularly. It is not clear whether immune function can be \"improved\". Measuring aspects of immune function is possible but there is no one test that will define either the status or functional capacity of the immune system. Human studies are often limited by the ability to sample only blood or secretions such as saliva but it should be remembered that only 2% of lymphocytes circulate at any given time, which limits interpretation of data. We recommend assessing the functional capacity of the immune system by: measuring specific cell functions ex vivo. measuring in vivo responses to challenge, e. g. change in antibody in blood or response to antigens. determining the incidence and severity of infection in target populations during naturally occurring episodes or in response to attenuated pathogens.",
"title": "PASSCLAIM--gut health and immunity."
},
{
"docid": "MED-3221",
"text": "Background The finding reported in a previous paper - alkalization of urine facilitates uric acid excretion - is contradictory to what one might expect to occur: because food materials for the alkalization of urine contain fewer purine bodies than those for acidification, less uric acid in alkaline urine should have been excreted than in acid urine. To make clear what component of uric acid excretion mechanisms is responsible for this unexpected finding, we simultaneously collected data for the concentration of both creatinine and uric acid in serum as well as in urine, in order to calculate both uric acid and creatinine clearances. Methods Within the framework of the Japanese government’s health promotion program, we made recipes which consisted of protein-rich and less vegetable-fruit food materials for H + -load (acidic diet) and others composed of less protein and more vegetable-fruit rich food materials (alkaline diet). This is a crossover study within some limitations. Healthy female students, who had no medical problems at the regular physical examination provided by the university, were enrolled in this consecutive 5-day study for each test. From whole-day collected urine, total volume, pH, organic acid, creatinine, uric acid, titratable acid and all cations (Na+,K+,Ca2+,Mg2+,NH4+) and anions (Cl−,SO42−,PO4−) necessary for the estimation of acid–base balance were measured. In the early morning before breakfast of the 1st, 3rd and 5th experimental day, we sampled 5 mL of blood to estimate the creatinine and uric acid concentration in serum. Results and discussion Urine pH reached a steady state 3 days after switching from ordinary daily diets to specified regimens. The amount of acid generated ([SO42−] + organic acid − gut alkali)was linearly related with the excretion of acid (titratable acid + [NH4+] − [HCO3−]), indicating that H + in urine is generated by the metabolic degradation of food materials. Uric acid and excreted urine pH retained a linear relationship, as reported previously. Among the five factors which are associated with calculating clearances for both uric acid and creatinine, we identified a conspicuous difference between acidic and alkaline diets in the uric acid concentration in serum as well as in urine; uric acid in the serum was higher in the acidic group than in the alkaline group, while uric acid in the urine in the acidic group was lower than that in the alkaline group. These changes of uric acid in acidic urine and in serum were reflected in the reduction of its clearance. From these observations, it is considered that uric acid may be reabsorbed more actively in acidic urine than in alkaline urine. Conclusion We conclude that alkalization of urine by eating nutritionally well-designed alkaline -prone food is effective for removing uric acid from the body.",
"title": "Effect of urine pH changed by dietary intervention on uric acid clearance mechanism of pH-dependent excretion of urinary uric acid"
},
{
"docid": "MED-2488",
"text": "Cardiovascular diseases (CVD) cost Americans billions of dollars per year. High cholesterol levels, which are closely related to dietary habits, are a major contributor to CVD. In this article, we study whether changes in food prices are related to cholesterol levels and whether taxes or subsidies on particular foods would be effective in lowering cholesterol levels and, consequently, CVD costs. We find that prices of vegetables, processed foods, whole milk and whole grains are significantly associated with blood cholesterol levels. Having analyzed the costs and benefits of government interventions, we find that a subsidy of vegetables and whole grains would be an efficient way to reduce CVD expenditures. Published by Elsevier B.V.",
"title": "Food prices and blood cholesterol."
},
{
"docid": "MED-2179",
"text": "OBJECTIVE: To investigate the association between cooking behaviour and long-term survival among elderly Taiwanese. DESIGN: Cohort study. The duration of follow-up was the interval between the date of interview and the date of death or 31 December 2008, when censored for survivors. Information used included demographics, socio-economic status, health behaviours, cooking frequencies, physical function, cognitive function, nutrition knowledge awareness, eating out habits and food and nutrient intakes. These data were linked to death records. Cox proportional-hazards models were used to evaluate cooking frequency on death from 1999 to 2008 with related covariate adjustments. SETTING: Elderly Nutrition and Health Survey in Taiwan, 1999-2000. SUBJECTS: Nationally representative free-living elderly people aged ≥65 years (n 1888). RESULTS: During a 10-year follow-up, 695 participants died. Those who cooked most frequently were younger, women, unmarried, less educated, non-drinkers of alcohol, non-smokers, without chewing difficulty, had spouse as dinner companion, normal cognition, who walked or shopped more than twice weekly, who ate less meat and more vegetables. Highly frequent cooking (>5 times/week, compared with never) predicted survival (hazard ratio (HR) = 0·47; 95 % CI, 0·36, 0·61); with adjustment for physical function, cognitive function, nutrition knowledge awareness and other covariates, HR was 0·59 (95 % CI, 0·41, 0·86). Women benefited more from cooking more frequently than did men, with decreased HR, 51 % v. 24 %, when most was compared with least. A 2-year delay in the assessment of survivorship led to similar findings. CONCLUSIONS: Cooking behaviour favourably predicts survivorship. Highly frequent cooking may favour women more than men.",
"title": "Cooking frequency may enhance survival in Taiwanese elderly."
},
{
"docid": "MED-3793",
"text": "OBJECTIVES: To determine cross-cultural and other effects on women's experiences of premenstrual symptoms and their impact on activities of daily life (ADL). STUDY DESIGN: Cross-sectional survey. Sample A total of 7226 women aged 15-49 recruited by random sampling with approximately 400 each from France, Germany, Hungary, Italy, Spain, UK, Brazil, Mexico, Hong Kong, Pakistan and Thailand. Approximately 1000 women in Japan and Korea and 500 Australian women were found using Internet panels. MAIN OUTCOME MEASURES: Questionnaire of 23 premenstrual symptoms, sociodemographic and lifestyle variables, ADL and women's knowledge of premenstrual terms. RESULTS: The most prevalent symptoms were abdominal bloating, cramps or abdominal pain, irritability, mastalgia and joint/muscle/back pains. Severity of symptoms was directly proportional to duration (number of affected cycles) (R = 0.78). A linear model found that symptom prevalence (duration × severity) was associated with age (linear and quadratic effects), parity, current smoking and country. Premenstrual physical and mental symptom domains had similar negative effects on ADL. Impact on ADL was affected by education and exercise participation. Women's knowledge of the terms premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) varied by symptom intensity, age, education and country. CONCLUSIONS: Four of the five most prevalent premenstrual symptoms were physical. There was a great deal of similarities of women's experiences of these symptoms across countries and regions. Women's knowledge of PMS terms is highly dependent on the country in which they live.",
"title": "Global study of women's experiences of premenstrual symptoms and their effects on daily life."
},
{
"docid": "MED-1499",
"text": "Nature has gifted mankind with a plethora of flora-bearing fruits, vegetables and nuts. The diverse array of bioactive nutrients present in these natural products plays a pivotal role in prevention and cure of various neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease and other neuronal dysfunctions. Accumulated evidence suggests that naturally occurring phyto-compounds, such as polyphenolic antioxidants found in fruits, vegetables, herbs and nuts, may potentially hinder neurodegeneration, and improve memory and cognitive function. Nuts such as walnut have also demonstrated neuroprotective effect against AD. The molecular mechanisms behind the curative effects rely mainly on the action of phytonutrients on distinct signalling pathways associated with protein folding and neuroinflammation. The neuroprotective effects of various naturally occurring compounds in AD is evaluating in this review.",
"title": "Neuroprotective effect of natural products against Alzheimer's disease."
},
{
"docid": "MED-3275",
"text": "In tissue cultures of normal adult and malignant mammalian cells, homocystine has been substituted for methionine in a medium rich in folic acid and cyanocobalamin. Normal adult cells thrive. Three highly malignant cell types from three different species, including man, die.",
"title": "The Effect of Replacement of Methionine by Homocystine on Survival of Malignant and Normal Adult Mammalian Cells in Culture"
},
{
"docid": "MED-4612",
"text": "Amino acids modulate the secretion of both insulin and glucagon; the composition of dietary protein therefore has the potential to influence the balance of glucagon and insulin activity. Soy protein, as well as many other vegan proteins, are higher in non-essential amino acids than most animal-derived food proteins, and as a result should preferentially favor glucagon production. Acting on hepatocytes, glucagon promotes (and insulin inhibits) cAMP-dependent mechanisms that down-regulate lipogenic enzymes and cholesterol synthesis, while up-regulating hepatic LDL receptors and production of the IGF-I antagonist IGFBP-1. The insulin-sensitizing properties of many vegan diets--high in fiber, low in saturated fat--should amplify these effects by down-regulating insulin secretion. Additionally, the relatively low essential amino acid content of some vegan diets may decrease hepatic IGF-I synthesis. Thus, diets featuring vegan proteins can be expected to lower elevated serum lipid levels, promote weight loss, and decrease circulating IGF-I activity. The latter effect should impede cancer induction (as is seen in animal studies with soy protein), lessen neutrophil-mediated inflammatory damage, and slow growth and maturation in children. In fact, vegans tend to have low serum lipids, lean physiques, shorter stature, later puberty, and decreased risk for certain prominent 'Western' cancers; a vegan diet has documented clinical efficacy in rheumatoid arthritis. Low-fat vegan diets may be especially protective in regard to cancers linked to insulin resistance--namely, breast and colon cancer--as well as prostate cancer; conversely, the high IGF-I activity associated with heavy ingestion of animal products may be largely responsible for the epidemic of 'Western' cancers in wealthy societies. Increased phytochemical intake is also likely to contribute to the reduction of cancer risk in vegans. Regression of coronary stenoses has been documented during low-fat vegan diets coupled with exercise training; such regimens also tend to markedly improve diabetic control and lower elevated blood pressure. Risk of many other degenerative disorders may be decreased in vegans, although reduced growth factor activity may be responsible for an increased risk of hemorrhagic stroke. By altering the glucagon/insulin balance, it is conceivable that supplemental intakes of key non-essential amino acids could enable omnivores to enjoy some of the health advantages of a vegan diet. An unnecessarily high intake of essential amino acids--either in the absolute sense or relative to total dietary protein--may prove to be as grave a risk factor for 'Western' degenerative diseases as is excessive fat intake.",
"title": "Vegan proteins may reduce risk of cancer, obesity, and cardiovascular disease by promoting increased glucagon activity."
},
{
"docid": "MED-1868",
"text": "Obesity is associated with a great diversity of diseases including non-alcoholic fatty liver disease. Our previous report suggested that Hibiscus sabdariffa extracts (HSE) had a metabolic-regulating and liver-protecting potential. In this study, we performed a clinical trial to further confirm the effect of HSE. Subjects with a BMI ≧ 27 and aged 18-65, were randomly divided into control (n = 17) and HSE-treated (n = 19) groups, respectively, for 12 weeks. Our data showed that consumption of HSE reduced body weight, BMI, body fat and the waist-to-hip ratio. Serum free fatty acid (FFA) was lowered by HSE. Anatomic changes revealed that HSE improved the illness of liver steatosis. Ingestion of HSE was well tolerated and there was no adverse effect during the trial. No alteration was found for serum α-amylase and lipase. The clinical effect should mainly be attributed to the polyphenols of HSE, since composition analysis showed that branched chain-amino acids, which is associated with obesity, is not obviously high. In conclusion, consumption of HSE reduced obesity, abdominal fat, serum FFA and improved liver steatosis. HSE could act as an adjuvant for preventing obesity and non-alcoholic fatty liver.",
"title": "Hibiscus sabdariffa extract inhibits obesity and fat accumulation, and improves liver steatosis in humans."
},
{
"docid": "MED-1874",
"text": "It is likely that plant food consumption throughout much of human evolution shaped the dietary requirements of contemporary humans. Diets would have been high in dietary fiber, vegetable protein, plant sterols and associated phytochemicals, and low in saturated and trans-fatty acids and other substrates for cholesterol biosynthesis. To meet the body's needs for cholesterol, we believe genetic differences and polymorphisms were conserved by evolution, which tended to raise serum cholesterol levels. As a result modern man, with a radically different diet and lifestyle, especially in middle age, is now recommended to take medications to lower cholesterol and reduce the risk of cardiovascular disease. Experimental introduction of high intakes of viscous fibers, vegetable proteins and plant sterols in the form of a possible Myocene diet of leafy vegetables, fruit and nuts, lowered serum LDL-cholesterol in healthy volunteers by over 30%, equivalent to first generation statins, the standard cholesterol-lowering medications. Furthermore, supplementation of a modern therapeutic diet in hyperlipidemic subjects with the same components taken as oat, barley and psyllium for viscous fibers, soy and almonds for vegetable proteins and plant sterol-enriched margarine produced similar reductions in LDL-cholesterol as the Myocene-like diet and reduced the majority of subjects' blood lipids concentrations into the normal range. We conclude that reintroduction of plant food components, which would have been present in large quantities in the plant based diets eaten throughout most of human evolution into modern diets can correct the lipid abnormalities associated with contemporary eating patterns and reduce the need for pharmacological interventions.",
"title": "The Garden of Eden--plant based diets, the genetic drive to conserve cholesterol and its implications for heart disease in the 21st century."
},
{
"docid": "MED-4107",
"text": "Background: The American Heart Association (AHA), Institute of Medicine (IOM), and US Departments of Health and Human Services and Agriculture (USDA) Dietary Guidelines for Americans all recommend that Americans limit sodium intake and choose foods that contain potassium to decrease the risk of hypertension and other adverse health outcomes. Objective: We estimated the distributions of usual daily sodium and potassium intakes by sociodemographic and health characteristics relative to current recommendations. Design: We used 24-h dietary recalls and other data from 12,581 adults aged ≥20 y who participated in NHANES in 2003–2008. Estimates of sodium and potassium intakes were adjusted for within-individual day-to-day variation by using measurement error models. SEs and 95% CIs were assessed by using jackknife replicate weights. Results: Overall, 99.4% (95% CI: 99.3%, 99.5%) of US adults consumed more sodium daily than recommended by the AHA (<1500 mg), and 90.7% (89.6%, 91.8%) consumed more than the IOM Tolerable Upper Intake Level (2300 mg). In US adults who are recommended by the Dietary Guidelines to further reduce sodium intake to 1500 mg/d (ie, African Americans aged ≥51 y or persons with hypertension, diabetes, or chronic kidney disease), 98.8% (98.4%, 99.2%) overall consumed >1500 mg/d, and 60.4% consumed >3000 mg/d—more than double the recommendation. Overall, <2% of US adults and ∼5% of US men consumed ≥4700 mg K/d (ie, met recommendations for potassium). Conclusion: Regardless of recommendations or sociodemographic or health characteristics, the vast majority of US adults consume too much sodium and too little potassium.",
"title": "Sodium and potassium intakes among US adults: NHANES 2003–2008"
},
{
"docid": "MED-3795",
"text": "Mastalgia affects up to two-thirds of women at some time during their reproductive lives. It is usually benign, but thefear of underlying breast cancer is why many women present for evaluation. Mastalgia can be associated with premenstrual syndrome, fibrocystic breast disease, psychologic disturbance and, rarely, breast cancer. Occasionally, extramammary conditions, like Tietzie syndrome, present as mastalgia. A thorough clinical evaluation is required to assess the cause. The majority of women can be reassured after a clinical evaluation. Approximately 15% require pain-relieving therapy. Mechanical breast support; a low-fat, high-carbohydrate diet; and topical nonsteroidal antiinflammatory agents are reasonable first-line treatments. Hormonal agents, such as bromocriptine, tamoxifen and danazol, have all demonstrated efficacy in the treatment of mastalgia. Side effects, however, limit their extensive use. Danazol is the only FDA-approved hormonal treatment and is best used in cyclic form to limit the adverse effects. Lisuride maleate is a new agent recently studied for the treatment of mastalgia. Initial data on this medication are encouraging. Sixty percent of cyclic mastalgia recurs after treatment. Noncyclic mastalgia responds poorly to treatment but resolves spontaneously in up to 50% of cases.",
"title": "Mastalgia: a review of management."
},
{
"docid": "MED-4313",
"text": "BACKGROUND: Population-based studies have shown that vegetarians have lower body mass index than nonvegetarians, suggesting that vegetarian diet plans may be an approach for weight management. However, a perception exists that vegetarian diets are deficient in certain nutrients. OBJECTIVE: To compare dietary quality of vegetarians, nonvegetarians, and dieters, and to test the hypothesis that a vegetarian diet would not compromise nutrient intake when used to manage body weight. DESIGN: Cross-sectional analysis of National Health and Nutrition Examination Survey (1999-2004) dietary and anthropometric data. Diet quality was determined using United States Department of Agriculture's Healthy Eating Index 2005. Participants included adults aged 19 years and older, excluding pregnant and lactating women (N = 13,292). Lacto-ovo vegetarian diets were portrayed by intakes of participants who did not eat meat, poultry, or fish on the day of the survey (n = 851). Weight-loss diets were portrayed by intakes of participants who consumed 500 kcal less than their estimated energy requirements (n = 4,635). Mean nutrient intakes and body mass indexes were adjusted for energy, sex, and ethnicity. Using analysis of variance, all vegetarians were compared to all nonvegetarians, dieting vegetarians to dieting nonvegetarians, and nondieting vegetarians to nondieting nonvegetarians. RESULTS: Mean intakes of fiber, vitamins A, C, and E, thiamin, riboflavin, folate, calcium, magnesium, and iron were higher for all vegetarians than for all nonvegetarians. Although vegetarian intakes of vitamin E, vitamin A, and magnesium exceeded that of nonvegetarians (8.3 ± 0.3 vs 7.0 ± 0.1 mg; 718 ± 28 vs 603 ± 10 μg; 322 ± 5 vs 281 ± 2 mg), both groups had intakes that were less than desired. The Healthy Eating Index score did not differ for all vegetarians compared to all nonvegetarians (50.5 ± 0.88 vs 50.1 ± 0.33, P = 0.6). CONCLUSIONS: These findings suggest that vegetarian diets are nutrient dense, consistent with dietary guidelines, and could be recommended for weight management without compromising diet quality. Copyright © 2011 American Dietetic Association. Published by Elsevier Inc. All rights reserved.",
"title": "A vegetarian dietary pattern as a nutrient-dense approach to weight management: an analysis of the national health and nutrition examination survey..."
},
{
"docid": "MED-3112",
"text": "The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor present in many cells. The AhR links environmental chemical stimuli with adaptive responses, such as detoxification, cellular homoeostasis or immune responses. Furthermore, novel roles of AhR in physiological and genetic functions are being discovered. This is a report of a recent meeting in Düsseldorf. The meeting highlighted that AhR research has moved from its focus on toxic effects of dioxins and other environmental pollutants to its biological roles. For instance, it was recently discovered that AhR-responsive elements in retrotransposons contribute to the functional structure of the genome. Other exciting new reports concerned the way plant-derived compounds in our diet are necessary for a fully functioning immune system of the gut. Also, human brain tumours use the AhR system to gain growth advantages. Other aspects covered were neurotoxicology, the circadian rhythm, or the breadth of the adaptive and innate immune system (hematopoietic stem cells, dendritic cells, T cells, mast cells). Finally, the meeting dealt with the discovery of new xenobiotic and natural ligands and their use in translational medicine, or cancer biology and AhR.",
"title": "Biology and function of the aryl hydrocarbon receptor: report of an international and interdisciplinary conference."
},
{
"docid": "MED-2093",
"text": "Chlorhexidine (CHX) is one of the most commonly prescribed antiseptic agents in the dental field. It has a long-lasting antibacterial activity with a broad-spectrum of action and it has been shown to reduce plaque, gingival inflammation and bleeding. Its use is considered a powerful adjuvant to mechanical oral hygiene (brushing and flossing), especially in those cases in which it cannot be performed correctly. Available as mouthwash, gel, aerosol, spray and disks, CHX is considered a safe compound, with minimal and transitory local and systemic side effects. Data support its periodic use as an adjuvant to normal brushing and flossing in subjects unable to maintain proper oral hygiene due to physical and/or mental impairment, or lack of motivation, or decreased salivary rate. CHX is also a useful alternative to mechanical oral hygiene procedures in those cases in which they are contraindicated, e.g. after a surgical procedure, or as a preoperative rinse before procedures in which use of a dental dam is not possible. The aim of this article is to offer a complete review of literature regarding the characteristics, the applications and the problems associated with the use of chlorhexidine in the dental field.",
"title": "Chlorhexidine (CHX) in dentistry: state of the art."
},
{
"docid": "MED-1819",
"text": "Gemcitabine is a first line cancer drug widely used for the treatment of pancreatic cancer. However, its therapeutic efficiency is significantly limited by resistance of pancreatic cancer cells to this and other chemotherapeutic drugs. We have investigated the cytotoxic effect of Turmeric Force (TF), a supercritical and hydroethanolic extract of turmeric, alone and in combination with gemcitabine in two pancreatic carcinoma cell lines (BxPC3 and Panc-1). TF is highly cytotoxic to BxPC3 and Panc-1 cell lines with IC50 values of 1.0 and 1.22 microg/ml, respectively with superior cytotoxicity than curcumin. Gemcitabine IC50 value for both of these cell line is 0.03 microg/ml; however, 30-48% of the pancreatic cancer cells are resistant to gemcitabine even at concentrations >100 microg/ml. In comparison, TF induced cell death in 96% of the cells at 50 microg/ml. The combination of gemcitabine and TF was synergistic with IC90 levels achieved in both pancreatic cancer cell lines at lower concentrations. CalcuSyn analysis of cytotoxicity data showed that the Gemcitabine + Turmeric Force combination has strong synergism with combination index (CI) values of 0.050 and 0.183 in BxPC3 and Panc-1 lines, respectively at IC50 level. This synergistic effect is due to the increased inhibitory effect of the combination on nuclear factor-kappaB activity and signal transducer and activator of transcription factor 3 expression as compared to the single agent.",
"title": "Potentiation of gemcitabine by Turmeric Force in pancreatic cancer cell lines."
},
{
"docid": "MED-1504",
"text": "BACKGROUND: Numerous studies have investigated risk factors for Alzheimer disease (AD). However, at a recent National Institutes of Health State-of-the-Science Conference, an independent panel found insufficient evidence to support the association of any modifiable factor with risk of cognitive decline or AD. OBJECTIVE: To present key findings for selected factors and AD risk that led the panel to their conclusion. DATA SOURCES: An evidence report was commissioned by the Agency for Healthcare Research and Quality. It included English-language publications in MEDLINE and the Cochrane Database of Systematic Reviews from 1984 through October 27, 2009. Expert presentations and public discussions were considered. STUDY SELECTION: Study inclusion criteria for the evidence report were participants aged 50 years and older from general populations in developed countries; minimum sample sizes of 300 for cohort studies and 50 for randomized controlled trials; at least 2 years between exposure and outcome assessment; and use of well-accepted diagnostic criteria for AD. DATA EXTRACTION: Included studies were evaluated for eligibility and data were abstracted. Quality of overall evidence for each factor was summarized as low, moderate, or high. DATA SYNTHESIS: Diabetes mellitus, hyperlipidemia in midlife, and current tobacco use were associated with increased risk of AD, and Mediterranean-type diet, folic acid intake, low or moderate alcohol intake, cognitive activities, and physical activity were associated with decreased risk. The quality of evidence was low for all of these associations. CONCLUSION: Currently, insufficient evidence exists to draw firm conclusions on the association of any modifiable factors with risk of AD.",
"title": "Risk factors and preventive interventions for Alzheimer disease: state of the science."
},
{
"docid": "MED-3217",
"text": "To investigate whether systemic acid-base equilibrium changes with aging in normal adult humans, we reviewed published articles reporting the acid-base composition of arterial, arterialized venous, or capillary blood in age-identified healthy subjects. We extracted or calculated blood hydrogen ion concentration ([H+]), plasma bicarbonate concentration ([HCO3(-)]), blood PCO2, and age, and computed a total of 61 age-group means, distributed among eight 10-year intervals from age 20 to 100 years. Using linear regression analysis, we found that with increasing age, there is a significant increase in the steady-state blood [H+] (p < .001), and reduction in steady-state plasma [HCO3(-)] (p < .001), indicative of a progressively worsening low-level metabolic acidosis. Blood PCO2 decreased with age (p < .05), in keeping with the expected respiratory adaptation to metabolic acidosis. Such age-related increasing metabolic acidosis may reflect in part the normal decline of renal function with increasing age. The role of age-related metabolic acidosis in the pathogenesis of the degenerative diseases of aging warrants consideration.",
"title": "Age and systemic acid-base equilibrium: analysis of published data."
},
{
"docid": "MED-2575",
"text": "Introduction Matrix metalloproteinases (MMPs) have repeatedly been shown to play a very active role in extracellular matrix degradation associated with tumor invasion and metastasis. Tissue inhibitors of MMPs (TIMPs) are well-known for their ability to inhibit MMP activity thereby inhibiting malignant progression. Inositol hexaphosphate (IP6 phytic acid) has been recognized to have both preventive and therapeutic effects against various cancers including that of colon. In in vitro studies, IP6 has been demonstrated to inhibit cancer cell adhesion and migration. In the present study, the effect of IP6 on the expression of MMP and TIMP genes was evaluated in unstimulated and IL-1β-stimulated colon cancer cell line Caco-2. Materials and methods Real-time QRT-PCR was used to validate the transcription level of selected MMP and TIMP genes in Caco-2 cells after treatment with 1 ng/ml of IL-1β, 2.5 mM of IP6, and both for 6, 12, and 24 h. Results Stimulation of cells with IL-1β only resulted in an overexpression of MMP and their TIMP mRNAs. A significant decrease in MMP-13, MMP-3, MMP-2, and TIMP-1 basal expression was achieved by IP6. IP6 was also an efficient downregulator of MMP-1, MMP-9, and TIMP-2 genes transcription stimulated by IL-1β in 6 h lasting culture. After 12 h, IL-1β-induced MMP-2 mRNA expression was significantly reduced by IP6. Conclusion Proinflammatory cytokine IL-1β upregulates MMP and TIMP mRNAs expression in colon cancer epithelial cells Caco-2. IP6 (2.5 mM) influences constitutive expression of both MMP and TIMP genes and downregulates IL-1β stimulated transcription of some of these genes. IP6 exerts its anti-metastatic activity through modulation of MMP and TIMP genes expression to prevent cancer cell migration and invasion.",
"title": "The effect of inositol hexaphosphate on the expression of selected metalloproteinases and their tissue inhibitors in IL-1β-stimulated colon cancer cells"
},
{
"docid": "MED-2238",
"text": "Rose G (Department of Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK). Sick individuals and sick populations. International Journal of Epidemiology 1985;14:32--38. Aetiology confronts two distinct issues: the determinants of individual cases, and the determinants of incidence rate. If exposure to a necessary agent is homogeneous within a population, then case/control and cohort methods will fail to detect it: they will only identify markers of susceptibility. The corresponding strategies in control are the 'high-risk' approach, which seeks to protect susceptible individuals, and the population approach, which seeks to control the causes of incidence. The two approaches are not usually in competition, but the prior concern should always be to discover and control the causes of incidence.",
"title": "Sick individuals and sick populations."
},
{
"docid": "MED-2804",
"text": "Osteoarthritis (OA) is the most common form of arthritis in the US, and a leading cause of disability. It is typically defined in epidemiologic studies on the basis of radiographic findings and consideration of symptoms. Its incidence and prevalence are rising, likely related to the aging of the population and increasing obesity. Risk factors for OA include a number of person-level factors, such as age, sex, obesity, and genetics, as well as joint-specific factors that are likely reflective of abnormal loading of the joints. A number of methodologic challenges exist in studying OA that can hamper our ability to identify pertinent relationships.",
"title": "Epidemiology of OA"
},
{
"docid": "MED-2797",
"text": "Osteoarthritis (OA) has long been considered a \"wear and tear\" disease leading to loss of cartilage. OA used to be considered the sole consequence of any process leading to increased pressure on one particular joint or fragility of cartilage matrix. Progress in molecular biology in the 1990s has profoundly modified this paradigm. The discovery that many soluble mediators such as cytokines or prostaglandins can increase the production of matrix metalloproteinases by chondrocytes led to the first steps of an \"inflammatory\" theory. However, it took a decade before synovitis was accepted as a critical feature of OA, and some studies are now opening the way to consider the condition a driver of the OA process. Recent experimental data have shown that subchondral bone may have a substantial role in the OA process, as a mechanical damper, as well as a source of inflammatory mediators implicated in the OA pain process and in the degradation of the deep layer of cartilage. Thus, initially considered cartilage driven, OA is a much more complex disease with inflammatory mediators released by cartilage, bone and synovium. Low-grade inflammation induced by the metabolic syndrome, innate immunity and inflammaging are some of the more recent arguments in favor of the inflammatory theory of OA and highlighted in this review. Copyright © 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.",
"title": "Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!)."
},
{
"docid": "MED-3215",
"text": "The average American diet, which is high in protein and low in fruits and vegetables, generates a large amount of acid, mainly as sulfates and phosphates. The kidneys respond to this dietary acid challenge with net acid excretion, as well as ammonium and titratable acid excretion. Concurrently, the skeleton supplies buffer by active resorption of bone. Indeed, calciuria is directly related to net acid excretion. Different food proteins differ greatly in their potential acid load, and therefore in their acidogenic effect. A diet high in acid-ash proteins causes excessive calcium loss because of its acidogenic content. The addition of exogenous buffers, as chemical salts or as fruits and vegetables, to a high protein diet results in a less acid urine, a reduction in net acid excretion, reduced ammonium and titratable acid excretion, and decreased calciuria. Bone resorption may be halted, and bone accretion may actually occur. Alkali buffers, whether chemical salts or dietary fruits and vegetables high in potassium, reverse acid-induced obligatory urinary calcium loss. We conclude that excessive dietary protein from foods with high potential renal acid load adversely affects bone, unless buffered by the consumption of alkali-rich foods or supplements.",
"title": "Excess dietary protein can adversely affect bone."
},
{
"docid": "MED-3229",
"text": "High-protein (HP) diets exert a hypercalciuric effect at constant levels of calcium intake, even though the effect may depend on the nature of the dietary protein. Lower urinary pH is also consistently observed for subjects consuming HP diets. The combination of these two effects was suspected to be associated with a dietary environment favorable for demineralization of the skeleton. However, increased calcium excretion due to HP diet does not seem to be linked to impaired calcium balance. In contrast, some data indicate that HP intakes induce an increase of intestinal calcium absorption. Moreover, no clinical data support the hypothesis of a detrimental effect of HP diet on bone health, except in a context of inadequate calcium supply. In addition, HP intake promotes bone growth and retards bone loss and low-protein diet is associated with higher risk of hip fractures. The increase of acid and calcium excretion due to HP diet is also accused of constituting a favorable environment for kidney stones and renal diseases. However, in healthy subjects, no damaging effect of HP diets on kidney has been found in either observational or interventional studies and it seems that HP diets might be deleterious only in patients with preexisting metabolic renal dysfunction. Thus, HP diet does not seem to lead to calcium bone loss, and the role of protein seems to be complex and probably dependent on other dietary factors and the presence of other nutrients in the diet.",
"title": "Protein intake, calcium balance and health consequences."
},
{
"docid": "MED-1869",
"text": "Observational and clinical studies suggest that high protein intake, particularly protein from plant sources, might reduce blood pressure (BP). To examine the association of dietary protein with BP, we analysed data from PREMIER, an 18-month clinical trial (n=810) that examined the effects of two multi-component lifestyle modifications on BP. We examined the association of protein intake with BP, and in particular the independent relationship of plant and animal protein with BP. Multivariable linear regression analyses were performed with both cross-sectional and longitudinal data. Dietary plant protein was inversely associated with both systolic and diastolic BP in cross-sectional analyses at the 6-month follow-up (P=0.0045 and 0.0096, respectively). Fruit and vegetable intake was also inversely associated with both systolic and diastolic BP cross-sectionally at 6 months (P=0.0003 and 0.0157, respectively). In longitudinal analyses, a high intake of plant protein at 6 months was marginally associated with a reduction of both systolic and diastolic BP from baseline to 6 months only (P=0.0797 and 0.0866, respectively), independent of change in body weight and waist circumference. Furthermore, increased intake of plant protein, and fruits and vegetables was significantly associated with a lower risk of hypertension at 6 but not at 18 months. Results of this study indicate that plant protein had a beneficial effect on BP and was associated with a lower risk of hypertension at 6 months. Our data, in conjunction with other research, suggest that an increased intake of plant protein may be useful as a means to prevent and treat hypertension.",
"title": "The relationship between dietary protein intake and blood pressure: results from the PREMIER study."
},
{
"docid": "MED-1414",
"text": "Considerable evidence suggests that the carcinogens or co-carcinogens responsible for the development of colorectal cancer are either bacterially degraded bile acids or cholesterol. It is proposed that a high colonic pH promotes co-carcinogen formation from these substances and that acidification of the colon either by dietary fibre (following its bacterial digestion to short-chain fatty acids) or milk (in lactose-intolerant individuals) may prevent this process.",
"title": "High colonic pH promotes colorectal cancer."
},
{
"docid": "MED-3276",
"text": "Methionine is an essential amino acid with many key roles in mammalian metabolism such as protein synthesis, methylation of DNA and polyamine synthesis. Restriction of methionine may be an important strategy in cancer growth control particularly in cancers that exhibit dependence on methionine for survival and proliferation. Methionine dependence in cancer may be due to one or a combination of deletions, polymorphisms or alterations in expression of genes in the methionine de novo and salvage pathways. Cancer cells with these defects are unable to regenerate methionine via these pathways. Defects in the metabolism of folate may also contribute to the methionine dependence phenotype in cancer. Selective killing of methionine dependent cancer cells in co-culture with normal cells has been demonstrated using culture media deficient in methionine. Several animal studies utilizing a methionine restricted diet have reported inhibition of cancer growth and extension of a healthy life-span. In humans, vegan diets, which can be low in methionine, may prove to be a useful nutritional strategy in cancer growth control. The development of methioninase which depletes circulating levels of methionine may be another useful strategy in limiting cancer growth. The application of nutritional methionine restriction and methioninase in combination with chemotherapeutic regimens is the current focus of clinical studies. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "A review of methionine dependency and the role of methionine restriction in cancer growth control and life-span extension."
},
{
"docid": "MED-4235",
"text": "We studied the obstruction-relieving capabilities of transurethral electrovaporization of the prostate (TVP) in 32 symptomatic patients with benign prostatic hyperplasia (BPH). Urodynamic studies with pressure-flow analysis were performed before and 6 months after treatment. All 32 patients showed significant improvement of both subjective and objective obstruction parameters. There were few postoperative irritative symptoms and one patient required recatheterization. In conclusion, TVP is a promising modification of performing transurethral resection of the prostate, and it is indeed capable of relieving bladder outflow obstruction.",
"title": "Transurethral electrovaporization of the prostate in benign prostatic hyperplasia. Evaluation of results using different urodynamic parameters."
},
{
"docid": "MED-1410",
"text": "In 15 cohorts of the Seven Countries Study, comprising 11,579 men aged 40-59 years and \"healthy\" at entry, 2,288 died in 15 years. Death rates differed among cohorts. Differences in mean age, blood pressure, serum cholesterol, and smoking habits \"explained\" 46% of variance in death rate from all causes, 80% from coronary heart disease, 35% from cancer, and 45% from stroke. Death rate differences were unrelated to cohort differences in mean relative body weight, fatness, and physical activity. The cohorts differed in average diets. Death rates were related positively to average percentage of dietary energy from saturated fatty acids, negatively to dietary energy percentage from monounsaturated fatty acids, and were unrelated to dietary energy percentage from polyunsaturated fatty acids, proteins, carbohydrates, and alcohol. All death rates were negatively related to the ratio of monounsaturated to saturated fatty acids. Inclusion of that ratio with age, blood pressure, serum cholesterol, and smoking habits as independent variables accounted for 85% of variance in rates of deaths from all causes, 96% coronary heart disease, 55% cancer, and 66% stroke. Oleic acid accounted for almost all differences in monounsaturates among cohorts. All-cause and coronary heart disease death rates were low in cohorts with olive oil as the main fat. Causal relationships are not claimed but consideration of characteristics of populations as well as of individuals within populations is urged in evaluating risks.",
"title": "The diet and 15-year death rate in the seven countries study."
},
{
"docid": "MED-2218",
"text": "OBJECTIVE: To determine prevalence of dementia and its subtypes in Japanese-American men and compare these findings with rates reported for populations in Japan and elsewhere. DESIGN AND SETTING: The Honolulu Heart Program is a prospective population-based study of cardiovascular disease established in 1965. Prevalence estimates were computed from cases identified at the 1991 to 1993 examination. Cognitive performance was assessed using standardized methods, instruments, and diagnostic criteria. PARTICIPANTS: Subjects were 3734 Japanese-American men (80% of surviving cohort) aged 71 through 93 years, living in the community or in institutions. MAIN OUTCOME MEASURES: Age-specific, age-standardized, and cohort prevalence estimates were computed for dementia (all cause) defined by 2 sets of diagnostic criteria and 4 levels of severity. Prevalence levels for Alzheimer disease and vascular dementia were also estimated. RESULTS: Dementia prevalence by Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised ranged from 2.1% in men aged 71 through 74 years to 33.4% in men aged 85 through 93 years. Age-standardized prevalence was 7.6%. Prevalence estimates for the cohort were 9.3% for dementia (all cause), 5.4% for Alzheimer disease (primary or contributing), and 4.2% for vascular dementia (primary or contributing). More than 1 possible cause was found in 26% of cases. The Alzheimer disease/vascular dementia ratio was 1.5 for cases attributed primarily to Alzheimer disease or vascular dementia. CONCLUSIONS: Prevalence of Alzheimer disease in older Japanese-American men in Hawaii appears to be higher than in Japan but similar to European-ancestry populations. Prevalence of vascular dementia appears to be slightly lower than in Japan, but higher than in European-ancestry populations. Further cross-national research with emphasis on standardized diagnostic methods is needed.",
"title": "Prevalence of dementia in older Japanese-American men in Hawaii: The Honolulu-Asia Aging Study."
},
{
"docid": "MED-3875",
"text": "BACKGROUND: Mammalian lignans, enterolactone (EL) and enterodiol (ED), have been shown to inhibit breast and colon carcinoma. To date, there have been no reports of the effect of lignans on prostatic carcinoma. We investigated the effects of ED and EL on three human prostate cancer cell lines (PC-3, DU-145 and LNCaP). MATERIALS AND METHODS: Cells were treated with either 0.1% (v/v) DMSO (vehicle) or 10-100 microM of EL, ED or genistein (positive control) for 72 hours. Cell viability was measured by the propidium iodide nuclei staining fluorometric assay with each assay performed in triplicate. RESULTS: At 10-100 microM, EL significantly inhibited the growth of all cell lines, whereas ED only inhibited PC-3 and LNCaP cells. While EL was a more potent growth inhibitor than ED, both were less potent than genistein. The dose for 50% growth inhibition of LNCaP cells (IC50) by EL was 57 microM, whereas IC50 was 100 microM for ED, (the observed IC50 for genistein was 25 microM). CONCLUSION: ED and EL suppress the growth of prostate cancer cells, and may do so via hormonally-dependent and independent mechanisms.",
"title": "Effect of mammalian lignans on the growth of prostate cancer cell lines."
},
{
"docid": "MED-4295",
"text": "Phytosterols were quantified in nuts and seeds commonly consumed in the United States. Total lipid extracts were subjected to acid hydrolysis and then alkaline saponfication, and free sterols were analyzed as trimethylsilyl derivatives by capillary GC-FID and GC-MS. Delta5-Avenasterol was quantified after alkaline saponification plus direct analysis of the glucoside. Sesame seed and wheat germ had the highest total phytosterol content (400-413 mg/100 g) and Brazil nuts the lowest (95 mg/100 g). Of the products typically consumed as snack foods, pistachio and sunflower kernel were richest in phytosterols (270-289 mg/100 g). beta-Sitosterol, Delta5-avenasterol, and campesterol were predominant. Campestanol ranged from 1.0 to 12.7 mg/100 g. Only 13 mg/100 g beta-sitosterol was found in pumpkin seed kernel, although total sterol content was high (265 mg/100 g). Phytosterol concentrations were greater than reported in existing food composition databases, probably due to the inclusion of steryl glycosides, which represent a significant portion of total sterols in nuts and seeds.",
"title": "Phytosterol composition of nuts and seeds commonly consumed in the United States."
},
{
"docid": "MED-3792",
"text": "Basal serum prolactin and serum oestradiol-17-beta concentrations were measured four times during one menstrual cycle in 20 women with severe cyclical mastalgia and normal to slightly fibroadenotic breasts. A group of 10 normal women who had never experienced mastalgia served as controls. Basal serum prolactin was significantly elevated in patients compared to normals, although within the normal range. Serum oestradiol concentrations did not differ in the two groups and were also within the normal range. A significant positive correlation between oestradiol and prolactin was found in patients and normals, but with larger prolactin levels in patients. The results point towards a prolactin secretory hypersensitivity for oestradiol in patients with cyclical mastalgia. Prolactin is considered a central factor in the eliciting of cyclical mastalgia.",
"title": "Serum prolactin and oestradiol levels in women with cyclical mastalgia."
},
{
"docid": "MED-2969",
"text": "OBJECTIVE: We have previously shown that 300 kcal from glucose intake induces a significant increase in reactive oxygen species (ROS) generation and nuclear factor-kappaB (NF-kappaB) binding in the circulating mononuclear cells in healthy normal subjects. We hypothesized that the intake of 300 calories as orange juice or fructose, the other major carbohydrate in orange juice, would induce a significantly smaller response than that of glucose. RESEARCH DESIGN AND METHODS: Four groups (eight subjects each) of normal-weight subjects were given a 300-cal drink of glucose (75 g), fructose (75 g), or orange juice or water sweetened with saccharin (control group) to drink, and then blood samples were collected. RESULTS: There was a significant increase in ROS generation by mononuclear cells (by 130 +/- 18%, P < 0.001), polymorph nuclear cells (by 95 +/- 22%, P < 0.01), and in NF-kappaB binding in mononuclear cells by 82 +/- 16% (P < 0.01) over the baseline after 2 h of glucose intake. These changes were absent following fructose, orange juice, or water intake. There was significantly lower ROS generation and NF-kappaB binding following orange juice, fructose, and water compared with glucose (P < 0.001 for all). Furthermore, incubation of mononuclear cells in vitro with 50 mmol/l of the flavonoids hesperetin or naringenin reduced ROS generation by 52 +/- 7% and 77 +/- 8% (P < 0.01), respectively, while fructose or ascorbic acid did not cause any change. CONCLUSIONS: Caloric intake in the form of orange juice or fructose does not induce either oxidative or inflammatory stress, possibly due to its flavonoids content and might, therefore, represent a potentially safe energy source.",
"title": "Orange juice or fructose intake does not induce oxidative and inflammatory response."
},
{
"docid": "MED-3270",
"text": "Aging affects all organisms and its basic mechanisms are expected to be conserved across species. Oxidation of proteins has been proposed to be one of the basic mechanisms linking oxygen radicals with the basic aging process. If oxidative damage to proteins is involved in aging, long-lived animals (which age slowly) should show lower levels of markers of this kind of damage than short-lived ones. However, this possibility has not been investigated yet. In this study, steady-state levels of markers of different kinds of protein damage--oxidation (glutamic and aminoadipic semialdehydes), mixed glyco- and lipoxidation (carboxymethyl- and carboxyethyllysine), lipoxidation (malondialdehydelysine) and amino acid composition--were measured in the heart of eight mammalian species ranging in maximum life span (MLSP) from 3.5 to 46 years. Oxidation markers were directly correlated with MLSP across species. Mixed glyco- and lipoxidation markers did not correlate with MLSP. However, the lipoxidation marker malondialdehydelysine was inversely correlated with MLSP (r2=0.85; P<0.001). The amino acid compositional analysis revealed that methionine is the only amino acid strongly correlated MLSP and that such correlation is negative (r2=0.93; P<0.001). This trait may contribute to lower steady-state levels of oxidized methionine residues in cellular proteins. These results reinforce the notion that high longevity in homeothermic vertebrates is achieved in part by constitutively decreasing the sensitivity of both tissue proteins and lipids to oxidative damage. This is obtained by modifying the constituent structural components of proteins and lipids, selecting those less sensitive to oxidative modifications.",
"title": "Protein methionine content and MDA-lysine adducts are inversely related to maximum life span in the heart of mammals."
},
{
"docid": "MED-4506",
"text": "PURPOSE: Dietary nitrate supplementation has been shown to reduce the O2 cost of submaximal exercise and to improve high-intensity exercise tolerance. However, it is presently unknown whether it may enhance performance during simulated competition. The present study investigated the effects of acute dietary nitrate supplementation on power output (PO), VO2, and performance during 4- and 16.1-km cycling time trials (TT). METHODS: After familiarization, nine club-level competitive male cyclists were assigned in a randomized, crossover design to consume 0.5 L of beetroot juice (BR; containing ∼ 6.2 mmol of nitrate) or 0.5 L of nitrate-depleted BR (placebo, PL; containing ∼ 0.0047 mmol of nitrate), ∼ 2.5 h before the completion of a 4- and a 16.1-km TT. RESULTS: BR supplementation elevated plasma [nitrite] (PL = 241 ± 125 vs BR = 575 ± 199 nM, P < 0.05). The VO2 values during the TT were not significantly different between the BR and PL conditions at any elapsed distance (P > 0.05), but BR significantly increased mean PO during the 4-km (PL = 279 ± 51 vs BR = 292 ± 44 W, P < 0.05) and 16.1-km TT (PL = 233 ± 43 vs BR = 247 ± 44 W, P < 0.01). Consequently, BR improved 4-km performance by 2.8% (PL = 6.45 ± 0.42 vs BR = 6.27 ± 0.35 min, P < 0.05) and 16.1-km performance by 2.7% (PL = 27.7 ± 2.1 vs BR = 26.9 ± 1.8 min, P < 0.01). CONCLUSIONS: These results suggest that acute dietary nitrate supplementation with 0.5 L of BR improves cycling economy, as demonstrated by a higher PO for the same VO2 and enhances both 4- and 16.1-km cycling TT performance.",
"title": "Acute dietary nitrate supplementation improves cycling time trial performance."
},
{
"docid": "MED-2999",
"text": "Many of the commonest diseases in the economically more developed communities are characteristic of modern Western culture. Evidence is presented suggesting that they represent a failure of adaptation to the dramatic changes in diet that have been associated with the emergence of modern Western culture. Dietary changes aimed at the alleviation and prevention of these diseases are discussed and recommended.",
"title": "Western diseases and their emergence related to diet."
},
{
"docid": "MED-3697",
"text": "BACKGROUND: Many studies have analyzed the effect of behavioral risk factors such as common lifestyle patterns on the risk of disease. The aim of this study was to assess the effect of a healthy lifestyle index on the risk of breast cancer. METHODS: A population-based case-control study was conducted in Mexico from 2004 to 2007. One thousand incident cases and 1,074 controls, matched to cases by 5-year age category, region, and health institution, participated in the study. A healthy lifestyle index was developed by means of principal components by using dietary pattern, physical activity, alcohol consumption, and tobacco smoking. A conditional logistic regression model was used to assess this association. RESULTS: The healthy lifestyle index was defined as the combined effect of moderate and/or vigorous-intensity physical activity, low consumption of fat, processed foods, refined cereals, complex sugars, and the avoidance of tobacco smoking and alcohol consumption. Results showed a protective effect on both pre- (OR = 0.50, 95% CI: 0.29-0.84) and postmenopausal women (OR = O.20, 95% CI: 0.11-0.37) when highest versus lowest index quintiles were compared. CONCLUSIONS: Healthy lifestyle was associated with a reduction in the odds of having breast cancer. Primary prevention of this disease should be promoted in an integrated manner. Effective strategies need to be identified to engage women in healthy lifestyles. IMPACT: This study is the first to assess a healthy lifestyle index in relation to the risk of breast cancer. ©2011 AACR.",
"title": "Healthy lifestyle on the risk of breast cancer."
},
{
"docid": "MED-4319",
"text": "The article gives an overview of phytic acid in food and of its significance for human nutrition. It summarises phytate sources in foods and discusses problems of phytic acid/phytate contents of food tables. Data on phytic acid intake are evaluated and daily phytic acid intake depending on food habits is assessed. Degradation of phytate during gastro-intestinal passage is summarised, the mechanism of phytate interacting with minerals and trace elements in the gastro-intestinal chyme described and the pathway of inositol phosphate hydrolysis in the gut presented. The present knowledge of phytate absorption is summarised and discussed. Effects of phytate on mineral and trace element bioavailability are reported and phytate degradation during processing and storage is described. Beneficial activities of dietary phytate such as its effects on calcification and kidney stone formation and on lowering blood glucose and lipids are reported. The antioxidative property of phytic acid and its potentional anticancerogenic activities are briefly surveyed. Development of the analysis of phytic acid and other inositol phosphates is described, problems of inositol phosphate determination and detection discussed and the need for standardisation of phytic acid analysis in foods argued.",
"title": "Phytate in foods and significance for humans: food sources, intake, processing, bioavailability, protective role and analysis."
},
{
"docid": "MED-1211",
"text": "Objectives. We examined temporal and regional trends in the prevalence of health lifestyles in the United States. Methods. We used 1994 to 2007 data from the Behavioral Risk Factor Surveillance System to assess 4 healthy lifestyle characteristics: having a healthy weight, not smoking, consuming fruits and vegetables, and engaging in physical activity. The concurrent presence of all 4 characteristics was defined as a healthy overall lifestyle. We used logistic regression to assess temporal and regional trends. Results. The percentages of individuals who did not smoke (4% increase) and had a healthy weight (10% decrease) showed the strongest temporal changes from 1994 to 2007. There was little change in fruit and vegetable consumption or physical activity. The prevalence of healthy lifestyles increased minimally over time and varied modestly across regions; in 2007, percentages were higher in the Northeast (6%) and West (6%) than in the South (4%) and Midwest (4%). Conclusions. Because of the large increases in overweight and the declines in smoking, there was little net change in the prevalence of healthy lifestyles. Despite regional differences, the prevalence of healthy lifestyles across the United States remains very low.",
"title": "Temporal and Regional Trends in the Prevalence of Healthy Lifestyle Characteristics: United States, 1994–2007"
},
{
"docid": "MED-3142",
"text": "AIM: Soy foods are the major source of isoflavones, which are believed to play important roles in genesis of breast cancer and its progression. We here conducted a prospective study to evaluate the association of soy isoflavone food consumption with breast cancer prognosis. METHODS: A prospective study was performed from January 2004 and January 2006 in China. Trained interviewers conducted face-to-face interviews using a structured questionnaire to collect information on dietary habits and potential confounding factors. The relative risk [hazard ratio (HR)] and 95% CI were calculated from the Cox regression model for all significant predictors from cancer diagnosis to the endpoint of the study (event). RESULTS: After a median follow up of 52.1 months (range, 9-60 months), a total of 79 breast cancer related deaths were recorded in our study, risk being inversely associated with a high intake of soy isoflavone. With an average intake of soy isoflavone above 17.3 mg/day, the mortality of breast cancer can be reduced by about 38-36%. We also found the decreased breast cancer death with high soy protein intake, with a HR (95% CI) of 0.71 (0.52-0.98). Stratified analysis with reference to the ER status, further demonstrated a better prognosis of ER positive breast cancer with a high intake of soy isoflavone (HR 0.59, 0.40-0.93). CONCLUSION: Our study shows the soy food intake is associated with longer survival and low recurrence among breast cancer patients. A cohort study with a larger sample size and long term follow-up is now needed.",
"title": "Positive effects of soy isoflavone food on survival of breast cancer patients in China."
},
{
"docid": "MED-4180",
"text": "The aim was to determine half-life of six most abundant PCB congeners in the body of early adolescents. In 304 environmentally exposed children, PCB serum concentration was determined at the age of 8 and 12years. Half-life was determined for each child assuming exponential decrease or for the whole cohort using multiple regression. Results obtained by both approaches were in agreement. PCB reuptakes corrupting half-life estimates for each child and each congener were evaluated. If one of the serum PCB concentration values fell below the level of detection (LOD) the pair was excluded and if PCB half-life value exceeded the arbitrary value of 30years. The following median half-lives in years 4.46, 10.59, 9.7, 4.7, 9.1 and 9.8 were obtained for PCB congeners 118, 138(+163), 153, 156(+171), 170 and 180, respectively. The elimination half-life values were not systematically related to PCB serum concentration at any examination age. Between half-life values, percentage of children with significant reuptakes and PCB congener abundance in serum were found significant associations. Copyright © 2010 Elsevier Ltd. All rights reserved.",
"title": "Half-lives of serum PCB congener concentrations in environmentally exposed early adolescents."
},
{
"docid": "MED-1188",
"text": "One hundred and eighteen missionaries working on 75 mission stations or hospitals in 24 sub-Saharan African countries provided information about their medical practice in the preceding year of 1981. Details were collected of the total number of patients seen and admitted during the year, and the number of cases of bloody diarrhoea, typhoid and inflammatory bowel disease. Over 1 million outpatients and about 190,000 inpatients were treated. These included 12,859 cases of bloody diarrhoea, of whom 1,914 had typhoid. Twenty-two cases of inflammatory bowel disease were also reported. Histological support was least available in West Africa and only 25% of hospitals had access to this facility. Nevertheless, the frequency with which inflammatory bowel disease in sub-Saharan Africa is difficult and limited by access to diagnostic facilities. It is likely to be some time before reliable estimates of the incidence and prevalence of Crohn's disease and ulcerative colitis in the rural African population can be made.",
"title": "Inflammatory bowel disease in rural sub-Saharan Africa: rarity of diagnosis in patients attending mission hospitals."
},
{
"docid": "MED-1501",
"text": "BACKGROUND: Many biological, behavioral, social, and environmental factors may contribute to the delay or prevention of cognitive decline. PURPOSE: To summarize evidence about putative risk and protective factors for cognitive decline in older adults and the effects of interventions for preserving cognition. DATA SOURCES: English-language publications in MEDLINE, HuGEpedia, AlzGene, and the Cochrane Database of Systematic Reviews from 1984 through 27 October 2009. STUDY SELECTION: Observational studies with 300 or more participants and randomized, controlled trials (RCTs) with 50 or more adult participants who were 50 years or older, drawn from general populations, and followed for at least 1 year were included. Relevant, good-quality systematic reviews were also eligible. DATA EXTRACTION: Information on study design, outcomes, and quality were extracted by one researcher and verified by another. An overall rating of the quality of evidence was assigned by using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria. DATA SYNTHESIS: 127 observational studies, 22 RCTs, and 16 systematic reviews were reviewed in the areas of nutritional factors; medical factors and medications; social, economic, or behavioral factors; toxic environmental exposures; and genetics. Few of the factors had sufficient evidence to support an association with cognitive decline. On the basis of observational studies, evidence that supported the benefits of selected nutritional factors or cognitive, physical, or other leisure activities was limited. Current tobacco use, the apolipoprotein E epsilon4 genotype, and certain medical conditions were associated with increased risk. One RCT found a small, sustained benefit from cognitive training (high quality of evidence) and a small RCT reported that physical exercise helps to maintain cognitive function. LIMITATIONS: The categorization and definition of exposures were heterogeneous. Few studies were designed a priori to assess associations between specific exposures and cognitive decline. The review included only English-language studies, prioritized categorical outcomes, and excluded small studies. CONCLUSION: Few potentially beneficial factors were identified from the evidence on risk or protective factors associated with cognitive decline, but the overall quality of the evidence was low. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality and the National Institute on Aging, through the Office of Medical Applications of Research, National Institutes of Health.",
"title": "Systematic review: factors associated with risk for and possible prevention of cognitive decline in later life."
},
{
"docid": "MED-2580",
"text": "Adequate fruit and vegetable intake was suggested to protect against colorectal cancer and colorectal adenomas; however, several recent prospective studies reported no association. We examined the association between fruits and vegetables and adenomatous polyp recurrence in the Polyp Prevention Trial (PPT). The PPT was a low-fat, high-fiber, high-fruit, and vegetable dietary intervention trial of adenoma recurrence, in which there were no differences in the rate of adenoma recurrence in participants in the intervention and control arms of the trial. In this analysis of the entire PPT trial–based cohort, multiple logistic regression analysis was used to estimate the odds ratio (OR) of advanced and nonadvanced adenoma recurrence within quartiles of baseline and change (baseline minus the mean over 3 y) in fruit and vegetable intake, after adjustment for age, total energyy intake, use of nonsteroidal anti-inflammatory drugs, BMI, and gender. There were no significant associations between nonadvanced adenoma recurrence and overall change in fruit and vegetable consumption; however, those in the highest quartile of change in dry bean intake (greatest increase) compared with those in the lowest had a significantly reduced OR for advanced adenoma recurrence (OR = 0.35; 95% CI, 0.18–0.69; P for trend = 0.001). The median in the highest quartile of change in dry bean intake was 370% higher than the baseline intake. The PPT trial–based cohort provides evidence that dry beans may be inversely associated with advanced adenoma recurrence.",
"title": "High Dry Bean Intake and Reduced Risk of Advanced Colorectal Adenoma Recurrence among Participants in the Polyp Prevention Trial"
},
{
"docid": "MED-2111",
"text": "Coronary artery disease is essentially nonexistent in cultures whose nutrition assures cholesterol levels <150 mg/dl. Patients with advanced coronary artery disease may abolish disease progression through a plant-based diet and cholesterol-lowering medication to achieve and maintain a total cholesterol <150 mg/dl.",
"title": "Updating a 12-year experience with arrest and reversal therapy for coronary heart disease (an overdue requiem for palliative cardiology)."
},
{
"docid": "MED-2117",
"text": "Recent evidence underlines the role of Western diet in the pathogenesis of acne. Acne is absent in populations consuming Palaeolithic diets with low glycaemic load and no consumption of milk or dairy products. Two randomized controlled studies, one of which is presented in this issue of Acta Dermato-Venereologica, have provided evidence for the beneficial therapeutic effects of low glycaemic load diets in acne. Epidemiological evidence confirms that milk consumption has an acne-promoting or acne-aggravating effect. Recent progress in understanding the nutrient-sensitive kinase mammalian target of rapamycin complex 1 (mTORC1) allows a new view of nutrient signalling in acne by both high glycaemic load and increased insulin-, IGF-1-, and leucine signalling due to milk protein consumption. Acne should be regarded as an mTORC1-driven disease of civilization, like obesity, type 2 diabetes and cancer induced by Western diet. Early dietary counselling of teenage acne patients is thus a great opportunity for dermatology, which will not only help to improve acne but may reduce the long-term adverse effects of Western diet on more serious mTORC1-driven diseases of civilization.",
"title": "Diet in acne: further evidence for the role of nutrient signalling in acne pathogenesis."
},
{
"docid": "MED-1496",
"text": "Oxidative stress (OS) and damages due to excessive reactive oxygen species (ROS) are common causes of injuries to cells and organisms. The prevalence of neurodegenerative diseases (ND) increases with aging and much of the research involving ROS and OS has emerged from works in this field. This text reviews some recent published articles about the role of OS in ND. Since there are many reviews in this field, the focus was centered in articles published recently. The Scientific Journals Directory supported by the Brazilian Ministry of Education Office for the Coordination of Higher Educational Personnel Improvement (CAPES) was used to search, download, and review articles. The search engine looked for the terms 'oxidative stress AND neurodegenerative diseases AND nutrition' in 10 different scientific collections. Biochemical markers for ND lack sensitivity or specificity for diagnosis or for tracking response to therapy today. OS has an intimate connection with ND, albeit low levels of ROS seem to protect the brain. Deleterious changes in mitochondria, OS, calcium, glucocorticoids, inflammation, trace metals, insulin, cell cycle, protein aggregation, and hundreds to thousands of genes occur in ND. The interaction of genes with their environment, may explain ND. Although OS has received much attention over the years, which increased the number of scientific works on antioxidant interventions, no one knows how to stop or delay ND at present. Interventions in vitro, in vivo, and in humans will continue to contribute for a better understanding of these pathologies.",
"title": "Brain rust: recent discoveries on the role of oxidative stress in neurodegenerative diseases."
},
{
"docid": "MED-5204",
"text": "It is generally accepted that carbohydrate fermentation results in beneficial effects for the host because of the generation of short chain fatty acids, whereas protein fermentation is considered detrimental for the host's health. Protein fermentation mainly occurs in the distal colon, when carbohydrates get depleted and results in the production of potentially toxic metabolites such as ammonia, amines, phenols and sulfides. However, the effectivity of these metabolites has been established mainly in in vitro studies. In addition, some important bowel diseases such as colorectal cancer (CRC) and ulcerative colitis appear most often in the distal colon, which is the primary site of protein fermentation. Finally, epidemiological studies revealed that diets rich in meat are associated with the prevalence of CRC, as is the case in Western society. Importantly, meat intake not only increases fermentation of proteins but also induces increased intake of fat, heme and heterocyclic amines, which may also play a role in the development of CRC. Despite these indications, the relationship between gut health and protein fermentation has not been thoroughly investigated. In this review, the existing evidence about the potential toxicity of protein fermentation from in vitro animal and human studies will be summarized. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",
"title": "Relevance of protein fermentation to gut health."
},
{
"docid": "MED-4333",
"text": "OBJECTIVE To evaluate the changes in circulating endotoxin after a high–saturated fat meal to determine whether these effects depend on metabolic disease state. RESEARCH DESIGN AND METHODS Subjects (n = 54) were given a high-fat meal (75 g fat, 5 g carbohydrate, 6 g protein) after an overnight fast (nonobese control [NOC]: age 39.9 ± 11.8 years [mean ± SD], BMI 24.9 ± 3.2 kg/m2, n = 9; obese: age 43.8 ± 9.5 years, BMI 33.3 ± 2.5 kg/m2, n = 15; impaired glucose tolerance [IGT]: age 41.7 ± 11.3 years, BMI 32.0 ± 4.5 kg/m2, n = 12; type 2 diabetic: age 45.4 ± 10.1 years, BMI 30.3 ± 4.5 kg/m2, n = 18). Blood was collected before (0 h) and after the meal (1–4 h) for analysis. RESULTS Baseline endotoxin was significantly higher in the type 2 diabetic and IGT subjects than in NOC subjects, with baseline circulating endotoxin levels 60.6% higher in type 2 diabetic subjects than in NOC subjects (P < 0.05). Ingestion of a high-fat meal led to a significant rise in endotoxin levels in type 2 diabetic, IGT, and obese subjects over the 4-h time period (P < 0.05). These findings also showed that, at 4 h after a meal, type 2 diabetic subjects had higher circulating endotoxin levels (125.4%↑) than NOC subjects (P < 0.05). CONCLUSIONS These studies have highlighted that exposure to a high-fat meal elevates circulating endotoxin irrespective of metabolic state, as early as 1 h after a meal. However, this increase is substantial in IGT and type 2 diabetic subjects, suggesting that metabolic endotoxinemia is exacerbated after high fat intake. In conclusion, our data suggest that, in a compromised metabolic state such as type 2 diabetes, a continual snacking routine will cumulatively promote their condition more rapidly than in other individuals because of the greater exposure to endotoxin.",
"title": "High Fat Intake Leads to Acute Postprandial Exposure to Circulating Endotoxin in Type 2 Diabetic Subjects"
},
{
"docid": "MED-2294",
"text": "The number of studies comparing nutritional quality of restrictive diets is limited. Data on vegan subjects are especially lacking. It was the aim of the present study to compare the quality and the contributing components of vegan, vegetarian, semi-vegetarian, pesco-vegetarian and omnivorous diets. Dietary intake was estimated using a cross-sectional online survey with a 52-items food frequency questionnaire (FFQ). Healthy Eating Index 2010 (HEI-2010) and the Mediterranean Diet Score (MDS) were calculated as indicators for diet quality. After analysis of the diet questionnaire and the FFQ, 1475 participants were classified as vegans (n = 104), vegetarians (n = 573), semi-vegetarians (n = 498), pesco-vegetarians (n = 145), and omnivores (n = 155). The most restricted diet, i.e., the vegan diet, had the lowest total energy intake, better fat intake profile, lowest protein and highest dietary fiber intake in contrast to the omnivorous diet. Calcium intake was lowest for the vegans and below national dietary recommendations. The vegan diet received the highest index values and the omnivorous the lowest for HEI-2010 and MDS. Typical aspects of a vegan diet (high fruit and vegetable intake, low sodium intake, and low intake of saturated fat) contributed substantially to the total score, independent of the indexing system used. The score for the more prudent diets (vegetarians, semi-vegetarians and pesco-vegetarians) differed as a function of the used indexing system but they were mostly better in terms of nutrient quality than the omnivores.",
"title": "Comparison of Nutritional Quality of the Vegan, Vegetarian, Semi-Vegetarian, Pesco-Vegetarian and Omnivorous Diet"
},
{
"docid": "MED-1204",
"text": "BACKGROUND: Plaque rupture and/or erosion is the leading cause of cardiovascular events; however, the process is not well understood. Although certain morphologic characteristics have been associated with ruptured plaques, these observations are of static histological images and not of the dynamics of plaque rupture. To elucidate the process of plaque rupture, we investigated the transformation of cholesterol from liquid to solid crystal to determine whether growing crystals are capable of injuring the plaque cap. HYPOTHESIS: We hypothesized that during cholesterol crystallization the spatial configuration rapidly changes, causing forceful expansion of sharp-edged crystals that can damage the plaque cap. METHODS: Two experiments were performed in vitro: first, cholesterol powder was melted in graduated cylinders and allowed to crystallize at room temperature. Volume changes from liquid to solid state were measured and timed. Second, thin biological membranes (20-40 microm) were put in the path of growing crystals to determine damage during crystallization. RESULTS: As cholesterol crystallized, the peak volume increased rapidly by up to 45% over 3 min and sharp-tipped crystals cut through and tore membranes. The amount of cholesterol and peak level of crystal growth correlated directly (r = 0.98; p < 0.01), as did the amount of cholesterol and rate of crystal growth (r = 0.99; p < 0.01). CONCLUSIONS: These observations suggest that crystallization of supersaturated cholesterol in atherosclerotic plaques can induce cap rupture and/or erosion. This novel insight may help in the development of therapeutic strategies that can alter cholesterol crystallization and prevent acute cardiovascular events.",
"title": "Cholesterol crystals cause mechanical damage to biological membranes: a proposed mechanism of plaque rupture and erosion leading to arterial thromb..."
},
{
"docid": "MED-3447",
"text": "To investigate the chemopreventive effects of seaweed on breast cancer, we have been studying the relationship between iodine and breast cancer. We found earlier that the seaweed, wakame, showed a suppressive effect on the proliferation of DMBA (dimethylbenz(a)anthracene)-induced rat mammary tumors, possibly via apoptosis induction. In the present study, powdered mekabu was placed in distilled water, and left to stand for 24 h at 4 degrees C. The filtered supernatant was used as mekabu solution. It showed an extremely strong suppressive effect on rat mammary carcinogenesis when used in daily drinking water, without toxicity. In vitro, mekabu solution strongly induced apoptosis in 3 kinds of human breast cancer cells. These effects were stronger than those of a chemotherapeutic agent widely used to treat human breast cancer. Furthermore, no apoptosis induction was observed in normal human mammary cells. In Japan, mekabu is widely consumed as a safe, inexpensive food. Our results suggest that mekabu has potential for chemoprevention of human breast cancer.",
"title": "Seaweed prevents breast cancer?"
},
{
"docid": "MED-2214",
"text": "Summary Background 100 years after the first description, Alzheimer's disease is one of the most disabling and burdensome health conditions worldwide. We used the Delphi consensus method to determine dementia prevalence for each world region. Methods 12 international experts were provided with a systematic review of published studies on dementia and were asked to provide prevalence estimates for every WHO world region, for men and women combined, in 5-year age bands from 60 to 84 years, and for those aged 85 years and older. UN population estimates and projections were used to estimate numbers of people with dementia in 2001, 2020, and 2040. We estimated incidence rates from prevalence, remission, and mortality. Findings Evidence from well-planned, representative epidemiological surveys is scarce in many regions. We estimate that 24·3 million people have dementia today, with 4·6 million new cases of dementia every year (one new case every 7 seconds). The number of people affected will double every 20 years to 81·1 million by 2040. Most people with dementia live in developing countries (60% in 2001, rising to 71% by 2040). Rates of increase are not uniform; numbers in developed countries are forecast to increase by 100% between 2001 and 2040, but by more than 300% in India, China, and their south Asian and western Pacific neighbours. Interpretation We believe that the detailed estimates in this paper constitute the best currently available basis for policymaking, planning, and allocation of health and welfare resources.",
"title": "Global prevalence of dementia: a Delphi consensus study"
},
{
"docid": "MED-1953",
"text": "Although garlic has been used for its medicinal properties for thousands of years, investigations into its mode of action are relatively recent. Garlic has a wide spectrum of actions; not only is it antibacterial, antiviral, antifungal and antiprotozoal, but it also has beneficial effects on the cardiovascular and immune systems. Resurgence in the use of natural herbal alternatives has brought the use of medicinal plants to the forefront of pharmacological investigations, and many new drugs are being discovered. This review aims to address the historical use of garlic and its sulfur chemistry, and to provide a basis for further research into its antimicrobial properties.",
"title": "Antimicrobial properties of Allium sativum (garlic)."
},
{
"docid": "MED-5293",
"text": "Summary Background Quantification of the disease burden caused by different risks informs prevention by providing an account of health loss different to that provided by a disease-by-disease analysis. No complete revision of global disease burden caused by risk factors has been done since a comparative risk assessment in 2000, and no previous analysis has assessed changes in burden attributable to risk factors over time. Methods We estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010. We estimated exposure distributions for each year, region, sex, and age group, and relative risks per unit of exposure by systematically reviewing and synthesising published and unpublished data. We used these estimates, together with estimates of cause-specific deaths and DALYs from the Global Burden of Disease Study 2010, to calculate the burden attributable to each risk factor exposure compared with the theoretical-minimum-risk exposure. We incorporated uncertainty in disease burden, relative risks, and exposures into our estimates of attributable burden. Findings In 2010, the three leading risk factors for global disease burden were high blood pressure (7·0% [95% uncertainty interval 6·2–7·7] of global DALYs), tobacco smoking including second-hand smoke (6·3% [5·5–7·0]), and alcohol use (5·5% [5·0–5·9]). In 1990, the leading risks were childhood underweight (7·9% [6·8–9·4]), household air pollution from solid fuels (HAP; 7·0% [5·6–8·3]), and tobacco smoking including second-hand smoke (6·1% [5·4–6·8]). Dietary risk factors and physical inactivity collectively accounted for 10·0% (95% UI 9·2–10·8) of global DALYs in 2010, with the most prominent dietary risks being diets low in fruits and those high in sodium. Several risks that primarily affect childhood communicable diseases, including unimproved water and sanitation and childhood micronutrient deficiencies, fell in rank between 1990 and 2010, with unimproved water we and sanitation accounting for 0·9% (0·4–1·6) of global DALYs in 2010. However, in most of sub-Saharan Africa childhood underweight, HAP, and non-exclusive and discontinued breastfeeding were the leading risks in 2010, while HAP was the leading risk in south Asia. The leading risk factor in Eastern Europe, most of Latin America, and southern sub-Saharan Africa in 2010 was alcohol use; in most of Asia, North Africa and Middle East, and central Europe it was high blood pressure. Despite declines, tobacco smoking including second-hand smoke remained the leading risk in high-income north America and western Europe. High body-mass index has increased globally and it is the leading risk in Australasia and southern Latin America, and also ranks high in other high-income regions, North Africa and Middle East, and Oceania. Interpretation Worldwide, the contribution of different risk factors to disease burden has changed substantially, with a shift away from risks for communicable diseases in children towards those for non-communicable diseases in adults. These changes are related to the ageing population, decreased mortality among children younger than 5 years, changes in cause-of-death composition, and changes in risk factor exposures. New evidence has led to changes in the magnitude of key risks including unimproved water and sanitation, vitamin A and zinc deficiencies, and ambient particulate matter pollution. The extent to which the epidemiological shift has occurred and what the leading risks currently are varies greatly across regions. In much of sub-Saharan Africa, the leading risks are still those associated with poverty and those that affect children. Funding Bill & Melinda Gates Foundation.",
"title": "A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010"
},
{
"docid": "MED-2801",
"text": "Turmeric has been long recognized for its anti-inflammatory and health-promoting properties. Curcumin is one of the principal anti-inflammatory and healthful components of turmeric comprising 2-8% of most turmeric preparations. Experimental evidence supports the activity of curcumin in promoting weight loss and reducing the incidence of obesity-related diseases. With the discovery that obesity is characterized by chronic low-grade metabolic inflammation, phytochemicals like curcumin which have anti-inflammatory activity are being intensely investigated. Recent scientific research reveals that curcumin directly interacts with white adipose tissue to suppress chronic inflammation. In adipose tissue, curcumin inhibits macrophage infiltration and nuclear factor κB (NF-κB) activation induced by inflammatory agents. Curcumin reduces the expression of the potent proinflammatory adipokines tumor necrosis factor-α (TNFα), monocyte chemoattractant protein-1 (MCP-1), and plasminogen activator inhibitor type-1 (PAI-1), and it induces the expression of adiponectin, the principal anti-inflammatory agent secreted by adipocytes. Curcumin also has effects to inhibit adipocyte differentiation and to promote antioxidant activities. Through these diverse mechanisms curcumin reduces obesity and curtails the adverse health effects of obesity. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.",
"title": "Curcumin and obesity."
},
{
"docid": "MED-1411",
"text": "OBJECTIVES: The aim of this study was to meta-analyze epidemiological studies and clinical trials that have assessed the effect of a Mediterranean diet on metabolic syndrome (MS) as well as its components. BACKGROUND: The Mediterranean diet has long been associated with low cardiovascular disease risk in adult population. METHODS: The authors conducted a systematic review and random effects meta-analysis of epidemiological studies and randomized controlled trials, including English-language publications in PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials until April 30, 2010; 50 original research studies (35 clinical trials, 2 prospective and 13 cross-sectional), with 534,906 participants, were included in the analysis. RESULTS: The combined effect of prospective studies and clinical trials showed that adherence to the Mediterranean diet was associated with reduced risk of MS (log hazard ratio: -0.69, 95% confidence interval [CI]: -1.24 to -1.16). Additionally, results from clinical studies (mean difference, 95% CI) revealed the protective role of the Mediterranean diet on components of MS, like waist circumference (-0.42 cm, 95% CI: -0.82 to -0.02), high-density lipoprotein cholesterol (1.17 mg/dl, 95% CI: 0.38 to 1.96), triglycerides (-6.14 mg/dl, 95% CI: -10.35 to -1.93), systolic (-2.35 mm Hg, 95% CI: -3.51 to -1.18) and diastolic blood pressure (-1.58 mm Hg, 95% CI: -2.02 to -1.13), and glucose (-3.89 mg/dl, 95% CI:-5.84 to -1.95), whereas results from epidemiological studies also confirmed those of clinical trials. CONCLUSIONS: These results are of considerable public health importance, because this dietary pattern can be easily adopted by all population groups and various cultures and cost-effectively serve for primary and secondary prevention of the MS and its individual components. Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.",
"title": "The effect of Mediterranean diet on metabolic syndrome and its components: a meta-analysis of 50 studies and 534,906 individuals."
},
{
"docid": "MED-2938",
"text": "Since the adoption of vegetarian diets as a healthy lifestyle has become popular, the cardiovascular effects of long-term vegetarianism need to be explored. The present study aimed to compare the presence and severity of carotid atherosclerosis (CA), and the blood levels of Vitamin B12, homocysteine (Hcy) and soluble vascular cell adhesion molecule-1 (sVCAM-1) between 57 healthy postmenopausal vegetarians and 61 age-matched omnivores. Carotid atherosclerosis, as measured by ultrasound, was found to be of no significant difference between the two groups. Yet, fasting blood glucose, low-density lipoprotein cholesterol, and Vitamin B12 were significantly lower, while Hcy and sVCAM-1 were higher in the vegetarians as comparing with the omnivores. Multivariate regression analysis showed that the level of Vitamin B12 was negatively associated with the level of Hcy. Vegetarianism itself and Hcy level were significantly associated with sVCAM-1 level in univariate analysis; however, after adjustment for covariates, we identified age but not vegetarianism as the determinant of sVCAM-1 level. Multiple linear regression analysis identified age and systolic blood pressure, but not vegetarianism, as determinants of common carotid artery IMT. In conclusion, there was no significant difference in CA between apparently healthy postmenopausal vegetarians and omnivores. The findings of elevated Hcy in vegetarians indicate the importance of prevention of Vitamin B12 deficiency.",
"title": "Homocysteine, circulating vascular cell adhesion molecule and carotid atherosclerosis in postmenopausal vegetarian women and omnivores."
},
{
"docid": "MED-2456",
"text": "Several studies have suggested that the increasing prevalence of symptoms of asthma, rhinitis and eczema, could be associated with dietary factors. In the present paper, a global analysis of prevalence rates of wheeze, allergic rhinoconjunctivitis and atopic eczema was performed in relation to diet, as defined by national food intake data. Analyses were based on the International Study of Asthma and Allergies in Childhood (ISAAC) data for 6-7 and 13-14 yr old children. Symptoms of wheeze, allergic rhinoconjunctivitis and atopic eczema symptom prevalence were regressed against per capita food intake, and adjusted for gross national product to account for economic development. Dietary data were based on 1995 Food and Agriculture Organisation of the United Nations data for 53 of the 56 countries that took part in ISAAC phase I (1994/1995). The 13-14 year age group showed a consistent pattern of decreases in symptoms of wheeze (current and severe), allergic rhinoconjunctivitis and atopic eczema, associated with increased per capita consumption of calories from cereal and rice, protein from cereals and nuts, starch, as well as vegetables and vegetable nutrients. The video questionnaire data for 13-14 yr olds and the ISAAC data for 6-7 yr olds showed similar patterns for these foods. A consistent inverse relationship was seen between prevalence rates of the three conditions and the intake of starch, cereals, and vegetables. If these findings could be generalised, and if the average daily consumption of these foods increased, it is speculated that an important decrease in symptom prevalence may be achieved.",
"title": "Diet and asthma, allergic rhinoconjunctivitis and atopic eczema symptom prevalence: an ecological analysis of the International Study of Asthma and..."
},
{
"docid": "MED-2458",
"text": "BACKGROUND: Antioxidant-rich diets are associated with reduced asthma prevalence in epidemiologic studies. We previously showed that short-term manipulation of antioxidant defenses leads to changes in asthma outcomes. OBJECTIVE: The objective was to investigate the effects of a high-antioxidant diet compared with those of a low-antioxidant diet, with or without lycopene supplementation, in asthma. DESIGN: Asthmatic adults (n = 137) were randomly assigned to a high-antioxidant diet (5 servings of vegetables and 2 servings of fruit daily; n = 46) or a low-antioxidant diet (≤2 servings of vegetables and 1 serving of fruit daily; n = 91) for 14 d and then commenced a parallel, randomized, controlled supplementation trial. Subjects who consumed the high-antioxidant diet received placebo. Subjects who consumed the low-antioxidant diet received placebo or tomato extract (45 mg lycopene/d). The intervention continued until week 14 or until an exacerbation occurred. RESULTS: After 14 d, subjects consuming the low-antioxidant diet had a lower percentage predicted forced expiratory volume in 1 s and percentage predicted forced vital capacity than did those consuming the high-antioxidant diet. Subjects in the low-antioxidant diet group had increased plasma C-reactive protein at week 14. At the end of the trial, time to exacerbation was greater in the high-antioxidant than in the low-antioxidant diet group, and the low-antioxidant diet group was 2.26 (95% CI: 1.04, 4.91; P = 0.039) times as likely to exacerbate. Of the subjects in the low-antioxidant diet group, no difference in airway or systemic inflammation or clinical outcomes was observed between the groups that consumed the tomato extract and those who consumed placebo. CONCLUSIONS: Modifying the dietary intake of carotenoids alters clinical asthma outcomes. Improvements were evident only after increased fruit and vegetable intake, which suggests that whole-food interventions are most effective. This trial was registered at http://www.actr.org.au as ACTRN012606000286549.",
"title": "Manipulating antioxidant intake in asthma: a randomized controlled trial."
},
{
"docid": "MED-2939",
"text": "Background: Vegetarianism is associated with a lower risk of cardiovascular disease. However, studies of arterial function in vegetarians are limited. Methods: This study investigated arterial function in vegetarianism by comparing 49 healthy postmenopausal vegetarians with 41 age-matched omnivores. The arterial function of the common carotid artery was assessed by carotid duplex, while the pulse dynamics method was used to measure brachial artery distensibility (BAD), compliance (BAC), and resistance (BAR). Fasting blood levels of glucose, lipids, lipoprotein (a), high-sensitivity C-reactive protein, homocysteine, and vitamin B12 were also measured. Results: Vegetarians had significantly lower serum cholesterol, high-density and low-density lipoprotein, and glucose compared with omnivores. They also had lower vitamin B12 but higher homocysteine levels. Serum levels of lipoprotein (a) and high-sensitivity C-reactive protein were no different between the two groups. There were no significant differences in carotid beta stiffness index, BAC, and BAD between the two groups even after adjustment for associated covariates. However, BAR was significantly lower in vegetarians than in omnivores. Multiple linear regression analysis revealed that age and pulse pressure were two important determinants of carotid beta stiffness index and BAD. Vegetarianism is not associated with better arterial elasticity. Conclusion: Apparently healthy postmenopausal vegetarians are not significantly better in terms of carotid beta stiffness index, BAC, and BAD, but have significantly decreased BAR than omnivores. Prevention of vitamin B12 deficiency might be beneficial for cardiovascular health in vegetarians.",
"title": "Arterial function of carotid and brachial arteries in postmenopausal vegetarians"
}
] |
[
{
"docid": "MED-4950",
"text": "Previously used standards for the diagnosis of precocious puberty in girls no longer appear to be appropriate in the USA, in that a significant number of girls are being seen in paediatricians' offices with breast budding before 8 years of age. The timing of menarche, however, has changed little over the past few decades. Early maturing girls are more likely to become obese in adolescence and adulthood than normal or late maturing girls. Early maturing white girls are heavier at the onset of puberty, but this is not the case for African-American girls or boys of either race. Boys and girls with premature pubarche may be more hyperinsulinaemic than normal children, and girls with premature pubarche more likely to develop functional ovarian and adrenal hyperandrogenism. Early menarche is preceded by prepubertal hyperinsulinaemia. It is proposed that pubertal onset, although not necessarily the tempo of puberty, is influenced by hyperinsulinaemia and insulin resistance. If this hypothesis is correct, insulin resistance may be more prevalent in US children than previously recognized. An advance in timing of onset of puberty has not been noted in other countries, although it is likely that this phenomenon may become more prevalent as other countries adopt a more American lifestyle and diet.",
"title": "The pubertal timing controversy in the USA, and a review of possible causative factors for the advance in timing of onset of puberty."
},
{
"docid": "MED-4104",
"text": "BACKGROUND: Although vegan diets improve diabetes management, little is known about the nutrient profiles or diet quality of individuals with type 2 diabetes who adopt a vegan diet. OBJECTIVE: To assess the changes in nutrient intake and dietary quality among participants following a low-fat vegan diet or the 2003 American Diabetes Association dietary recommendations. DESIGN: A 22-week randomized, controlled clinical trial examining changes in nutrient intake and diet quality. SUBJECTS/SETTING: Participants with type 2 diabetes (n=99) in a free-living setting. RESEARCH DESIGN AND METHODS: Participants were randomly assigned to a low-fat vegan diet or a 2003 American Diabetes Association recommended diet. MAIN OUTCOME MEASURES: Nutrient intake and Alternate Healthy Eating Index (AHEI) scores were collected at baseline and 22 weeks. STATISTICAL ANALYSES PERFORMED: Between-group t tests were calculated for changes between groups and paired comparison t tests were calculated for changes within-group. Pearson's correlation assessed relationship of AHEI score to hemoglobin A1c and body weight changes. RESULTS: Both groups reported significant decreases in energy, protein, fat, cholesterol, vitamin D, selenium, and sodium intakes. The vegan group also significantly reduced reported intakes of vitamin B-12 and calcium, and significantly increased carbohydrate, fiber, total vitamin A activity, beta carotene, vitamins K and C, folate, magnesium, and potassium. The American Diabetes Association recommended diet group also reported significant decreases in carbohydrate and iron, but reported no significant increases. The vegan group significantly improved its AHEI score (P<0.0001), while the American Diabetes Association recommended diet group did not (P=0.7218). The difference in AHEI score at 22 weeks between groups was significant (P<0.0001). With both groups combined, AHEI score was negatively correlated with both changes in hemoglobin A1c value (r=-0.24, P=0.016) and weight (r=-0.27, P=0.007). CONCLUSIONS: Vegan diets increase intakes of carbohydrate, fiber, and several micronutrients, in contrast with the American Diabetes Association recommended diet. The vegan group improved its AHEI score whereas the American Diabetes Association recommended diet group's AHEI score remained unchanged.",
"title": "Changes in nutrient intake and dietary quality among participants with type 2 diabetes following a low-fat vegan diet or a conventional diabetes di..."
},
{
"docid": "MED-5201",
"text": "It is estimated that most colon cancers can be attributed to dietary causes. We have hypothesized that diet influences the health of the colonic mucosa through interaction with the microbiota and that it is the milieu interior that regulates mucosal proliferation and therefore cancer risk. To validate this further, we compared colonic contents from healthy 50- to 65-y-old people from populations with high and low risk, specifically low risk Native Africans (cancer incidence <1:100,000; n = 17), high risk African Americans (risk 65:100,000; n = 17), and Caucasian Americans (risk 50:100,000; n = 18). Americans typically consume a high-animal protein and -fat diet, whereas Africans consume a staple diet of maize meal, rich in resistant starch and low in animal products. Following overnight fasting, rapid colonic evacuation was performed with 2 L polyethylene glycol. Total colonic evacuants were analyzed for SCFA, vitamins, nitrogen, and minerals. Total SCFA and butyrate were significantly higher in Native Africans than in both American groups. Colonic folate and biotin content, measured by Lactobacillus rhamnoses and Lactobacillus plantarum ATCC 8014 bioassay, respectively, exceeded normal daily dietary intakes. Compared with Africans, calcium and iron contents were significantly higher in Caucasian Americans and zinc content was significantly higher in African Americans, but nitrogen content did not differ among the 3 groups. In conclusion, the results support our hypothesis that the microbiota mediates the effect diet has on colon cancer risk by their generation of butyrate, folate, and biotin, molecules known to play a key role in the regulation of epithelial proliferation.",
"title": "Products of the colonic microbiota mediate the effects of diet on colon cancer risk."
},
{
"docid": "MED-1138",
"text": "PURPOSE: We compared the effect of 3 animal protein sources on urinary stone risk. MATERIALS AND METHODS: A total of 15 healthy subjects completed a 3-phase randomized, crossover metabolic study. During each 1-week phase subjects consumed a standard metabolic diet containing beef, chicken or fish. Serum chemistry and 24-hour urine samples collected at the end of each phase were compared using mixed model repeated measures analysis. RESULTS: Serum and urinary uric acid were increased for each phase. Beef was associated with lower serum uric acid than chicken or fish (6.5 vs 7.0 and 7.3 mg/dl, respectively, each p <0.05). Fish was associated with higher urinary uric acid than beef or chicken (741 vs 638 and 641 mg per day, p = 0.003 and 0.04, respectively). No significant difference among phases was noted in urinary pH, sulfate, calcium, citrate, oxalate or sodium. Mean saturation index for calcium oxalate was highest for beef (2.48), although the difference attained significance only compared to chicken (1.67, p = 0.02) but not to fish (1.79, p = 0.08). CONCLUSIONS: Consuming animal protein is associated with increased serum and urine uric acid in healthy individuals. The higher purine content of fish compared to beef or chicken is reflected in higher 24-hour urinary uric acid. However, as reflected in the saturation index, the stone forming propensity is marginally higher for beef compared to fish or chicken. Stone formers should be advised to limit the intake of all animal proteins, including fish. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.",
"title": "Animal protein and the risk of kidney stones: a comparative metabolic study of animal protein sources."
},
{
"docid": "MED-3592",
"text": "Levels of contaminants in fish are of particular interest because of the potential risk to humans who consume them. While attention has focused on self-caught fish, most of the fish eaten by the American public comes from commercial sources. We sampled 11 types of fish and shellfish obtained from supermarkets and specialty fish markets in New Jersey and analyzed them for arsenic, cadmium, chromium, lead, manganese, mercury, and selenium. We test the null hypothesis that metal levels do not vary among fish types, and we consider whether the levels of any metals could harm the fish themselves or their predators or pose a health risk for human consumers. There were significant interspecific differences for all metals, and no fish types had the highest levels of more than two metals. There were few significant correlations (Kendall tau) among metals for the three most numerous fish (yellowfin tuna, bluefish, and flounder), the correlations were generally low (below 0.40), and many correlations were negative. Only manganese and lead positively were correlated for tuna, bluefish, and flounder. The levels of most metals were below those known to cause adverse effects in the fish themselves. However, the levels of arsenic, lead, mercury, and selenium in some fish were in the range known to cause some sublethal effects in sensitive predatory birds and mammals and in some fish exceeded health-based standards. The greatest risk from different metals resided in different fish; the species of fish with the highest levels of a given metal sometimes exceeded the human health guidance or standards for that metal. Thus, the risk information given to the public (mainly about mercury) does not present a complete picture. The potential of harm from other metals suggests that people not only should eat smaller quantities of fish known to accumulate mercury but also should eat a diversity of fish to avoid consuming unhealthy quantities of other heavy metals. However, consumers should bear in mind that standards have a margin of safety.",
"title": "Heavy metals in commercial fish in New Jersey."
},
{
"docid": "MED-3295",
"text": "Background Few studies have investigated mortality in seafood workers worldwide, and no such study has been conducted in the United States. The objective of this study was to investigate mortality in American seafood workers. Methods The study population was derived from 4 states and consisted of 4116 subjects who worked mainly in seafood processing plants. They were followed up from 1966 to 2003. Standardized mortality ratios (SMRs) and proportional mortality ratios (PMRs) were estimated, using the US general population for comparison. Results About 45% of the cohort was born after 1949. A total of 788 deaths were recorded; 53% of the decedents were female, and 88% were white. The SMRs for stomach cancer and disorders of the thyroid gland in the cohort as a whole were 2.1 (95% confidence interval [CI], 1.1–3.8) and 6.1 (95% CI 1.3–18.0), respectively. The SMRs for breast cancer, and occlusion/stenosis of the pre-cerebral/cerebral arteries in the cohort as a whole were 0.5 (95% CI, 0.3–0.9) and 0.5 (95% CI, 0.2–0.8), respectively. The SMR for ischemic heart disease in white females was 0.8 (95% CI, 0.6–0.9). Conclusions This cohort had excess deaths from stomach cancer and disorders of the thyroid gland, and deficit of deaths from breast cancer, stroke and ischemic heart disease. The significance of these findings is unknown, especially as less than 20% of the cohort were deceased. Nevertheless, the cohort is unique and important, and further follow-up may shed more light on mortality patterns in this occupational group.",
"title": "Cancer and Noncancer Mortality Among American Seafood Workers"
},
{
"docid": "MED-1708",
"text": "High intakes of dietary sugars in the setting of a worldwide pandemic of obesity and cardiovascular disease have heightened concerns about the adverse effects of excessive consumption of sugars. In 2001 to 2004, the usual intake of added sugars for Americans was 22.2 teaspoons per day (355 calories per day). Between 1970 and 2005, average annual availability of sugars/added sugars increased by 19%, which added 76 calories to Americans' average daily energy intake. Soft drinks and other sugar-sweetened beverages are the primary source of added sugars in Americans' diets. Excessive consumption of sugars has been linked with several metabolic abnormalities and adverse health conditions, as well as shortfalls of essential nutrients. Although trial data are limited, evidence from observational studies indicates that a higher intake of soft drinks is associated with greater energy intake, higher body weight, and lower intake of essential nutrients. National survey data also indicate that excessive consumption of added sugars is contributing to overconsumption of discretionary calories by Americans. On the basis of the 2005 US Dietary Guidelines, intake of added sugars greatly exceeds discretionary calorie allowances, regardless of energy needs. In view of these considerations, the American Heart Association recommends reductions in the intake of added sugars. A prudent upper limit of intake is half of the discretionary calorie allowance, which for most American women is no more than 100 calories per day and for most American men is no more than 150 calories per day from added sugars.",
"title": "Dietary sugars intake and cardiovascular health: a scientific statement from the American Heart Association."
},
{
"docid": "MED-4095",
"text": "Statistics compiled by the National Cancer Institute indicate that, between 1935 and 1974, age-adjusted mortality from most 'Western' cancers (those of the breast, colon, prostate, pancreas, ovary, and kidney) rose dramatically in African-Americans. This phenomenon is paralleled by marked increases in the incidence of these cancers in Asia and Southern Europe during the latter 20th century, in conjunction with increased intakes of dietary animal products. A credible case can be made that diets rich in animal products work in various complementary ways to up-regulate serum levels of insulin, free IGF-I, and free sex hormones: hormones that appear to have important promotional activity for Western cancers. It seems likely that dietary animal product intake by black Americans increased substantially during the 20th century, and that this fact is primarily responsible for their concurrent marked increase in mortality from Western cancers. A whole-food vegan diet rich in fruits and vegetables, especially if coupled with regular exercise and smoking avoidance, could be expected to have a remarkably positive impact on African-American cancer risk, reversing the increases in cancer risk incurred during the 20th century. Copyright 2001 Harcourt Publishers Ltd.",
"title": "Mortality from Western cancers rose dramatically among African-Americans during the 20th century: are dietary animal products to blame?"
},
{
"docid": "MED-3718",
"text": "The American Cancer Society (ACS) publishes Nutrition and Physical Activity Guidelines to serve as a foundation for its communication, policy, and community strategies and ultimately, to affect dietary and physical activity patterns among Americans. These Guidelines, published every 5 years, are developed by a national panel of experts in cancer research, prevention, epidemiology, public health, and policy, and as such, they represent the most current scientific evidence related to dietary and activity patterns and cancer risk. The ACS Guidelines include recommendations for individual choices regarding diet and physical activity patterns, but those choices occur within a community context that either facilitates or interferes with healthy behaviors. Community efforts are essential to create a social environment that promotes healthy food choices and physical activity. Therefore, this committee presents one key recommendation for community action to accompany the four recommendations for individual choices to reduce cancer risk. This recommendation for community action recognizes that a supportive social environment is indispensable if individuals at all levels of society are to have genuine opportunities to choose healthy behaviors. The ACS Guidelines are consistent with guidelines from the American Heart Association and the American Diabetes Association for the prevention of coronary heart disease and diabetes, as well as for general health promotion, as defined by the Department of Health and Human Services' 2005 Dietary Guidelines for Americans.",
"title": "American Cancer Society Guidelines on Nutrition and Physical Activity for cancer prevention: reducing the risk of cancer with healthy food choices ..."
},
{
"docid": "MED-2592",
"text": "Background Studies have shown that pistachios can improve blood lipid profiles in subjects with moderate hypercholesterolemia which could reduce the risk of cardiovascular disease. However, there is also a widely perceived view that eating nuts can lead to body weight gain due to their high fat content. Purpose To investigate the impact of different dosages of pistachios on body weight, blood pressure, blood lipids, blood glucose and insulin in subjects with metabolic syndrome. Methods Ninety subjects with metabolic syndrome (consistent with 2005 International Diabetes Federation metabolic syndrome standard without diabetes) were enrolled in three endocrinology outpatient clinics in Beijing. All subjects received dietary counseling according to the guidelines of the American Heart Association Step I diet. After a 4 week run-in, subjects were randomized to consume either the recommended daily serving of 42 g pistachios (RSG), a higher daily serving of 70 g pistachio (HSG) or no pistachios (DCG) for 12 weeks. Results Subjects in all three groups were matched at baseline for BMI: DCG 28.03 ± 4.3; RSG 28.12 ± 3.22; and HSG 28.01 ± 4.51 kg/m2. There were no significant changes in body weight or BMI in any groups during the study nor any change from baseline at any time point in any group. During the entire study, there were no significant differences in waist-to-hip ratio among the groups or any change from baseline in any group (DCG -0.00 ± 0.03, RSG -0.01 ± 0.02 and HSG 0.01 ± 0.04). There were no significant differences detected among groups in triglycerides, fasting glucose and 2 hour postprandial glucose following a 75 gram glucose challenge. Exploratory analyses demonstrated that glucose values 2 h after a 75 gm glucose challenge were significantly lower at week 12 compared with baseline values in the HSG group (-1.13 ± 2.58 mmol/L, p = 0.02), and a similar trend was noted in the RSG group (-0.77 ± 2.07 mmol/L, p = 0.06), while no significant change was seen in the DCG group (-0.15 ± 2.27 mmol/L, p = 0.530). At the end of study, serum triglyceride levels were significantly lower compared with baseline in the RSG group (-0.38 ± 0.79 mmol/L, p = 0.018), but no significant changes were observed in the HSG or DCG groups. Conclusion Despite concerns that pistachio nut consumption may promote weight gain, the daily ingestion of either 42 g or 70 g of pistachios for 12 weeks did not lead to weight gain or an increase in waist-to-hip ratio in Chinese subjects with metabolic syndrome. In addition, pistachio consumption may improve the risk factor associated with the metabolic syndrome.",
"title": "Effects of pistachios on body weight in Chinese subjects with metabolic syndrome"
},
{
"docid": "MED-1887",
"text": "Some practitioners use advanced lipoprotein analysis with the goal of better predicting risk and individualizing lifestyle and drug therapy for cardiovascular prevention. Unfortunately, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particle number and size, other lipoprotein subfractionation, apolipoproteins B and A, and lipoprotein(a) have not yet met current standards for biomarker evaluation, and it remains to be determined whether these tests incrementally add to cardiovascular risk predicted by traditional risk factors. More importantly, it has yet to be determined whether treatment strategies guided by, or targeting, these measures improve cardiovascular outcomes. Drug therapies known to alter advanced lipoprotein analysis parameters, specifically niacin and fenofibrate, have not been shown to additionally reduce cardiovascular risk in recent randomized trials of high-risk patients treated with statin therapy. These findings suggest advanced lipoprotein analysis-guided strategies may not further reduce cardiovascular events and could lead to increased adverse effects and costs; this approach needs further research to establish its role in individualizing therapies for cardiovascular prevention. In contrast, a large body of evidence supports focusing on LDL cholesterol reduction and intensification of statin therapy to reduce cardiovascular risk. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.",
"title": "What is the role of advanced lipoprotein analysis in practice?"
},
{
"docid": "MED-5198",
"text": "The incidence of colorectal cancer (CRC) is dramatically higher in African Americans (AAs) than in Native Africans (NAs) (60:100,000 vs. <1:100,000) and slightly higher than in Caucasian Americans (CAs). To explore whether the difference could be explained by interactions between diet and colonic bacterial flora, we compared randomly selected samples of healthy 50- to 65-y-old AAs (n = 17) with NAs (n = 18) and CAs (n = 17). Diet was measured by 3-d recall, and colonic metabolism by breath hydrogen and methane responses to oral lactulose. Fecal samples were cultured for 7-alpha dehydroxylating bacteria and Lactobacillus plantarum. Colonoscopic mucosal biopsies were taken to measure proliferation rates. In comparison with NAs, AAs consumed more (P < 0.01) protein (94 +/- 9.3 vs. 58 +/- 4.1 g/d) and fat (114 +/- 11.2 vs. 38 +/- 3.0 g/d), meat, saturated fat, and cholesterol. However, they also consumed more (P < 0.05) calcium, vitamin A, and vitamin C, and fiber intake was the same. Breath hydrogen was higher (P < 0.0001) and methane lower in AAs, and fecal colony counts of 7-alpha dehydroxylating bacteria were higher and of Lactobacilli were lower. Colonic crypt cell proliferation rates were dramatically higher in AAs (21.8 +/- 1.1% vs. 3.2 +/- 0.8% labeling, P < 0.0001). In conclusion, the higher CRC risk and mucosal proliferation rates in AAs than in NAs were associated with higher dietary intakes of animal products and higher colonic populations of potentially toxic hydrogen and secondary bile-salt-producing bacteria. This supports our hypothesis that CRC risk is determined by interactions between the external (dietary) and internal (bacterial) environments.",
"title": "Why do African Americans get more colon cancer than Native Africans?"
},
{
"docid": "MED-5353",
"text": "We used the nationwide Swedish Family-Cancer Database to analyze cancer risks in Sweden-born descendants of immigrants from European and North American countries. Our study included close to 600,000 0-66-year-old descendants of an immigrant father or mother. We calculated standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for 17 cancer sites using native Swedes as a reference. All cancer was marginally below the Swedish incidence in offspring of immigrant origin. Decreased SIRs were observed for breast cancer among Norwegian descendants, melanoma among descendants of Hungarian fathers and ovarian and bladder cancer among descendents of Finnish mothers, all consistent with the difference in cancer incidence between Swedes and the indigenous populations. Cervical cancer was increased in daughters of Danish men, whereas thyroid cancer and non-Hodgkin's lymphoma were in excess in offspring of parents of Yugoslav and Asian descent. Even these results agreed with the high incidence rates in parents compared to Swedes, except that for non-Hodgkin's lymphoma other explanations are needed; these may be related to immune malfunction. Comparison of the results between the first- and the second-generation immigrants suggest that the first 2 decades of life are important in setting the pattern for cancer development in subsequent life. Birth in Sweden sets the Swedish pattern for cancer incidence, irrespective of the nationality of descent, while entering Sweden in the 20s is already too late to influence the environmentally imprinted program for the cancer destiny. Copyright 2002 Wiley-Liss, Inc.",
"title": "Cancer risks in second-generation immigrants to Sweden."
},
{
"docid": "MED-1548",
"text": "This document details the procedures and recommendations of the Goals and Metrics Committee of the Strategic Planning Task Force of the American Heart Association, which developed the 2020 Impact Goals for the organization. The committee was charged with defining a new concept, cardiovascular health, and determining the metrics needed to monitor it over time. Ideal cardiovascular health, a concept well supported in the literature, is defined by the presence of both ideal health behaviors (nonsmoking, body mass index <25 kg/m(2), physical activity at goal levels, and pursuit of a diet consistent with current guideline recommendations) and ideal health factors (untreated total cholesterol <200 mg/dL, untreated blood pressure <120/<80 mm Hg, and fasting blood glucose <100 mg/dL). Appropriate levels for children are also provided. With the use of levels that span the entire range of the same metrics, cardiovascular health status for the whole population is defined as poor, intermediate, or ideal. These metrics will be monitored to determine the changing prevalence of cardiovascular health status and define achievement of the Impact Goal. In addition, the committee recommends goals for further reductions in cardiovascular disease and stroke mortality. Thus, the committee recommends the following Impact Goals: \"By 2020, to improve the cardiovascular health of all Americans by 20% while reducing deaths from cardiovascular diseases and stroke by 20%.\" These goals will require new strategic directions for the American Heart Association in its research, clinical, public health, and advocacy programs for cardiovascular health promotion and disease prevention in the next decade and beyond.",
"title": "Defining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Association's strategic Impact Go..."
},
{
"docid": "MED-1307",
"text": "Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the United States. While the American Association for the Study of Liver Diseases guidelines define NAFLD as hepatic steatosis detected either on histology or imaging without a secondary cause of abnormal hepatic fat accumulation, no imaging modality is recommended as standard of care for screening or diagnosis. Bedside ultrasound has been evaluated as a non-invasive method of diagnosing NAFLD with the presence of characteristic sonographic findings. Prior studies suggest characteristic sonographic findings for NAFLD include bright hepatic echoes, increased hepatorenal echogenicity, vascular blurring of portal or hepatic vein and subcutaneous tissue thickness. These sonographic characteristics have not been shown to aid bedside clinicians easily identify potential cases of NAFLD. While sonographic findings such as attenuation of image, diffuse echogenicity, uniform heterogeneous liver, thick subcutaneous depth, and enlarged liver filling of the entire field could be identified by clinicians from bedside ultrasound. The accessibility, ease of use, and low-side effect profile of ultrasound make bedside ultrasound an appealing imaging modality in the detection of hepatic steatosis. When used with appropriate clinical risk factors and steatosis involves greater than 33% of the liver, ultrasound can reliably diagnose NAFLD. Despite the ability of ultrasound in detecting moderate hepatic steatosis, it cannot replace liver biopsy in staging the degree of fibrosis. The purpose of this review is to examine the diagnostic accuracy, utility, and limitations of ultrasound in the diagnosis of NAFLD and its potential use by clinicians in routine practices.",
"title": "Bedside ultrasound in the diagnosis of nonalcoholic fatty liver disease"
},
{
"docid": "MED-3088",
"text": "Elevated serum phosphorus is a major, preventable etiologic factor associated with the increased cardiovascular morbidity and mortality of dialysis patients. An important determinant of serum phosphorus is the dietary intake of this mineral; this makes dietary restriction of phosphorus a cornerstone for the prevention and treatment of hyperphosphatemia. The average daily dietary intake of phosphorus is about 1550 mg for males and 1000 mg for females. In general, foods high in protein are also high in phosphorus. These figures, however, are changing as phosphates are currently being added to a large number of processed foods including meats, cheeses, dressings, beverages, and bakery products. As a result, and depending on the food choices, such additives may increase the phosphorus intake by as a much as 1 g/day. Moreover, nutrient composition tables usually do not include the phosphorus from these additives, resulting in an underestimate of the dietary intake of phosphorus in our patients. Our goal is to convey an understanding of the phosphorus content of the current American diet to better equip nephrologists in their attempt to control hyperphosphatemia.",
"title": "Hidden sources of phosphorus in the typical American diet: does it matter in nephrology?"
},
{
"docid": "MED-1567",
"text": "INTRODUCTION: American Seventh-day Adventists have been reported to have lower cancer mortality and incidence than the general population. Adventists do not consume tobacco, alcohol or pork, and many adhere to a lacto-ovo-vegetarian lifestyle. Baptists discourage excessive use of alcohol and tobacco. In this study, we investigated whether the incidence of cancer in a large cohort of Danish Adventists and Baptists was different compared to the general Danish population. MATERIAL AND METHODS: We followed 11,580 Danish Adventists and Baptists in the nationwide Danish Cancer Registry, which contains information on cases of cancer for 1943-2008. Cancer incidence in the cohort was compared with that in the general Danish population as standardized incidence ratios (SIRs) with 95% confidence intervals (CIs), and within-cohort comparisons were made with a Cox model. RESULTS: Lower cancer incidences were observed for both Seventh-day Adventist men (SIR, 66; 95% CI, 60-72) and women (85; 80-91). The same result was observed for Baptists although not as low. The differences were most pronounced for smoking-related cancers such as those of the buccal cavity and lung (SIR, 20; 13-30 for Seventh-day Adventist men and 33; 22-49 for Seventh-day Adventist women). The incidences of other lifestyle-related cancers, such as of stomach, rectum, liver and cervix, were also decreased. In general, the SIRs were lower for men than for women, and Adventists had lower hazard rates than Baptists. DISCUSSION: Our findings point to the benefits of compliance with public health recommendations and indicate that lifestyle changes in the population might change the cancer risks of individuals. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Cancer incidence among Danish Seventh-day Adventists and Baptists."
},
{
"docid": "MED-5242",
"text": "PURPOSE: Epidemiological studies in women have revealed an association between caffeine intake and urinary incontinence, although evidence among men is limited. Therefore, we evaluated the association between caffeine intake and urinary incontinence in United States men. MATERIALS AND METHODS: Data were used from male NHANES (National Health and Nutrition Examination Surveys) 2005-2006 and 2007-2008 participants. Urinary incontinence was defined using a standard questionnaire with Incontinence Severity Index scores 3 or greater categorized as moderate to severe. Structured dietary recall was used to determine caffeine consumption (mg per day), water intake (gm per day) and total dietary moisture (gm per day). Stepwise multivariable logistic regression models were used to assess the association between caffeine intake at or above the 75th and 90th percentiles and moderate to severe urinary incontinence, controlling for potential confounders, urinary incontinence risk factors and prostate conditions in men age 40 years or older. RESULTS: Of the 5,297 men 3,960 (75%) were 20 years old or older with complete data. Among these men the prevalence of any urinary incontinence was 12.9% and moderate to severe urinary incontinence was 4.4%. Mean caffeine intake was 169 mg per day. Caffeine intake at the upper 75th percentile (234 mg or more daily) and 90th percentile (392 mg or more per day) was significantly associated with having moderate to severe urinary incontinence (1.72, 95% 1.18-2.49 and 2.08, 95% 1.15-3.77, respectively). In addition, after adjusting for prostate conditions, the effect size for the association between caffeine intake and moderate to severe urinary incontinence remained. CONCLUSIONS: Caffeine consumption equivalent to approximately 2 cups of coffee daily (250 mg) is significantly associated with moderate to severe urinary incontinence in United States men. Our findings support the further study of caffeine modification in men with urinary incontinence. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.",
"title": "Caffeine intake and its association with urinary incontinence in United States men: results from National Health and Nutrition Examination Surveys ..."
},
{
"docid": "MED-990",
"text": "OBJECTIVES: Elevated homocysteine has emerged as a risk factor for cognitive impairment even in healthy elderly persons. Reduced brain volume and white matter hyperintensities also occur in healthy elderly as well, but the interrelationships between these have not been well studied. We report these interrelationships in non demented, relatively healthy, community-dwelling older adults from a single East Asian population. METHODS: Two hundred twenty-eight right-handed participants age 55 years and above were evaluated. Persons with medical conditions or neurological diseases other than well-controlled diabetes mellitus and hypertension were excluded. Participants underwent quantitative magnetic resonance imaging of the brain using a standardized protocol and neuropsychological evaluation. Plasma homocysteine, folate, vitamin B(12), and markers for cardiovascular risk: blood pressure, body mass index, fasting blood glucose, and lipid profile were measured. RESULTS: Elevated homocysteine was associated with reduced global cerebral volume, larger ventricles, reduced cerebral white matter volume, and lower cognitive performance in several domains. Elevated homocysteine was associated with reduced white matter volume (β = -20.80, t = -2.9, df = 223, p = 0.004) and lower speed of processing (β = -0.38, t = -2.1, df = 223, p = 0.03), even after controlling for age, gender, and education. However, the association between homocysteine and lower speed of processing disappeared after controlling for white matter volume. Elevated homocysteine was not associated with white matter hyperintensity volume or with hippocampal volume. Although homocysteine and folate levels were correlated, their effects on white matter volume were dissociated. CONCLUSION: In non demented, relatively healthy adults, elevated homocysteine is associated with lower cognitive scores and reduced cerebral white matter volume. These effects can be dissociated from those related to white matter hyperintensities or reduced folate level. Copyright © 2013 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.",
"title": "Associations between elevated homocysteine, cognitive impairment, and reduced white matter volume in healthy old adults."
},
{
"docid": "MED-1179",
"text": "The US market for organic foods has grown from $3.5 billion in 1996 to $28.6 billion in 2010, according to the Organic Trade Association. Organic products are now sold in specialty stores and conventional supermarkets. Organic products contain numerous marketing claims and terms, only some of which are standardized and regulated. In terms of health advantages, organic diets have been convincingly demonstrated to expose consumers to fewer pesticides associated with human disease. Organic farming has been demonstrated to have less environmental impact than conventional approaches. However, current evidence does not support any meaningful nutritional benefits or deficits from eating organic compared with conventionally grown foods, and there are no well-powered human studies that directly demonstrate health benefits or disease protection as a result of consuming an organic diet. Studies also have not demonstrated any detrimental or disease-promoting effects from an organic diet. Although organic foods regularly command a significant price premium, well-designed farming studies demonstrate that costs can be competitive and yields comparable to those of conventional farming techniques. Pediatricians should incorporate this evidence when discussing the health and environmental impact of organic foods and organic farming while continuing to encourage all patients and their families to attain optimal nutrition and dietary variety consistent with the US Department of Agriculture's MyPlate recommendations. This clinical report reviews the health and environmental issues related to organic food production and consumption. It defines the term \"organic,\" reviews organic food-labeling standards, describes organic and conventional farming practices, and explores the cost and environmental implications of organic production techniques. It examines the evidence available on nutritional quality and production contaminants in conventionally produced and organic foods. Finally, this report provides guidance for pediatricians to assist them in advising their patients regarding organic and conventionally produced food choices.",
"title": "Organic foods: health and environmental advantages and disadvantages."
},
{
"docid": "MED-5218",
"text": "The effect of diet on tear function is illustrated clearly by malnutrition-induced xerophthalmia. Dietary habits in well nourished North American society have been implicated as a cause of some tear dysfunction. A review of the ocular literature suggests that sufficient dietary protein, vitamins A, B6 and C, potassium, and zinc may be necessary for normal tear function. Excesses of dietary fats, salt, cholesterol, alcohol, protein, and sucrose have been associated with or suggested as causes of tear dysfunction. No unequivocal link has been established between diet and remission of dry eye states in a well nourished population.",
"title": "Influence of diet on tear function."
},
{
"docid": "MED-1257",
"text": "Meat protein is associated with an increase in risk of heart disease. Recent data have shown that meat protein appeared to be associated with weight gain over 6.5 years, with 1 kg of weight increase per 125 g of meat per day. In the Nurses' Health Study, diets low in red meat, containing nuts, low-fat dairy, poultry, or fish, were associated with a 13% to 30% lower risk of CHD compared with diets high in meat. Low-carbohydrate diets high in animal protein were associated with a 23% higher total mortality rate whereas low-carbohydrate diets high in vegetable protein were associated with a 20% lower total mortality rate. Recent soy interventions have been assessed by the American Heart Association and found to be associated with only small reductions in LDL cholesterol. Although dairy intake has been associated with a lower weight and lower insulin resistance and metabolic syndrome, the only long-term (6 months) dairy intervention performed so far has shown no effects on these parameters.",
"title": "Protein and coronary heart disease: the role of different protein sources."
},
{
"docid": "MED-1991",
"text": "The objective of this article is to review the epidemiologic literature examining the role of plant foods and plant-based diets in the prevention of childhood obesity. Available data suggest a protective effect of ready-to-eat cereal on risk of obesity, although prospective studies are still needed. Studies on fruit and vegetables; grains other than cereal; high-protein foods, including beans, legumes, and soy; fiber; and plant-based dietary patterns are inconsistent or generally null. The evidence base is limited, and most studies are fraught with methodologic limitations, including cross-sectional design, inadequate adjustment for potential confounders, and lack of consideration of reporting errors, stage of growth, and genetic influences. Well-designed prospective studies are needed. The lack of evidence showing an association between plant-based diets and childhood obesity does not mean that such diets should not be encouraged. Plant foods are highlighted in the Dietary Guidelines for Americans, and children do not meet the current recommendations for most plant foods. Although the advice to consume a plant-based, low-energy-dense diet is sound, ethical questions arise concerning the relatively high price of these diets in the United States and the way in which such diets are perceived in other parts of the world. Reducing the burden of childhood obesity, eliminating health disparities, and preventing the further spread of the disease around the globe will require not only policy interventions to ensure that plant foods are affordable and accessible to children of all income levels but also awareness of sociocultural norms that affect consumption.",
"title": "Plant foods and plant-based diets: protective against childhood obesity?"
},
{
"docid": "MED-2717",
"text": "The United States is in the midst of a significant public health problem that relates to obesity and inactivity. This epidemic has far-ranging consequences for our workforce and our children and shows no signs of slowing in the near future. Significant research has been performed on the effects of exercise for the reduction of body weight; results of most studies indicate that exercise alone has a small effect on body-weight reduction independent of caloric restriction. However, when combined with dietary restriction, exercise has a synergistic effect and enhances weight loss beyond the effect of diet alone. In addition, exercise has been shown to have significant beneficial effects on cardiovascular and metabolic risk factors independent of actual weight loss, and losing just a small amount of weight can have a significant beneficial effect on these parameters. Genetic factors related to obesity have been found to be positively modified when persons incorporate physical activity into their lifestyle. Sitting time appears to be an independent risk factor for the development of metabolic risk factors; persons who spend more time sitting and watching television have worse metabolic profiles, even if they achieve the recommended amount of physical activity per week, than do those who move about throughout the day. Exercise also is essential for the prevention of weight gain over a life span, although the amount required to prevent weight gain may be closer to twice the amount of exercise recommended by the current Physical Activity Guidelines for Americans (www.health.gov/paguidelines). In many ways, the physiatrist is the most well prepared of all the specialists to address the complex, multidimensional problems of obesity and inactivity. Copyright © 2012 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.",
"title": "The role of exercise in the treatment of obesity."
},
{
"docid": "MED-5335",
"text": "Three recent case-control studies conclude that diets high in animal fat or cholesterol are associated with a substantial increase in risk for Parkinson's disease (PD); in contrast, fat of plant origin does not appear to increase risk. Whereas reported age-adjusted prevalence rates of PD tend to be relatively uniform throughout Europe and the Americas, sub-Saharan black Africans, rural Chinese, and Japanese, groups whose diets tend to be vegan or quasi-vegan, appear to enjoy substantially lower rates. Since current PD prevalence in African-Americans is little different from that in whites, environmental factors are likely to be responsible for the low PD risk in black Africans. In aggregate, these findings suggest that vegan diets may be notably protective with respect to PD. However, they offer no insight into whether saturated fat, compounds associated with animal fat, animal protein, or the integrated impact of the components of animal products mediates the risk associated with animal fat consumption. Caloric restriction has recently been shown to protect the central dopaminergic neurons of mice from neurotoxins, at least in part by induction of heat-shock proteins; conceivably, the protection afforded by vegan diets reflects a similar mechanism. The possibility that vegan diets could be therapeutically beneficial in PD, by slowing the loss of surviving dopaminergic neurons, thus retarding progression of the syndrome, may merit examination. Vegan diets could also be helpful to PD patients by promoting vascular health and aiding blood-brain barrier transport of L-dopa. Copyright 2001 Harcourt Publishers Ltd.",
"title": "Does a vegan diet reduce risk for Parkinson's disease?"
},
{
"docid": "MED-1747",
"text": "Knowledge of the US Public Health Syphilis Study at Tuskegee is sometime cited as a principal reason for the relatively low participation rates seen among racial/ethnic minorities, particularly African Americans, in biomedical research. However, only a few studies have actually explored this possibility. We use data from a random digit dial telephone survey of 510 African-Americans and 253 Latinos, age 18 to 45 years, to investigate associations between knowledge of the USPHS Syphilis Study at Tuskegee and endorsement of HIV/AIDS conspiracy theories. All respondents were drawn from an area of low-income, predominantly race-segregated inner city households in Los Angeles. Results indicate that African Americans were significantly more likely than Latinos to endorse HIV/AIDS conspiracy theories. Further, African Americans were more aware of the USPHS Syphilis Study at Tuskegee (SST). Nevertheless, 72% of African Americans and 94% of Latinos reported that they have never heard of the Syphilis Study at Tuskegee. Further, while awareness of the Syphilis Study at Tuskegee was a significant predictor of endorsing HIV/AIDS conspiracy theories, results suggest that other factors may be more important in accounting for low biomedical and behavioral study participation rates.",
"title": "Is there a legacy of the U.S. Public Health Syphilis Study at Tuskegee in HIV/AIDS-related beliefs among heterosexual African-Americans and Latinos?"
},
{
"docid": "MED-1565",
"text": "BACKGROUND: In 2007, the World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) issued recommendations on diet, physical activity, and weight management for cancer prevention on the basis of the most comprehensive collection of available evidence. OBJECTIVE: We investigated whether concordance with WCRF/AICR recommendations is related to risk of death. DESIGN: The current study included 378,864 participants from 9 European countries enrolled in the European Prospective Investigation into Cancer and Nutrition study. At recruitment (1992-1998), dietary, anthropometric, and lifestyle information was collected. A WCRF/AICR score, which incorporated 6 of the WCRF/AICR recommendations for men [regarding body fatness, physical activity, foods and drinks that promote weight gain, plant foods, animal foods, and alcoholic drinks (score range: 0-6)] and 7 WCRF/AICR recommendations for women [plus breastfeeding (score range: 0-7)], was constructed. Higher scores indicated greater concordance with WCRF/AICR recommendations. Associations between the WCRF/AICR score and risks of total and cause-specific death were estimated by using Cox regression analysis. RESULTS: After a median follow-up time of 12.8 y, 23,828 deaths were identified. Participants within the highest category of the WCRF/AICR score (5-6 points in men; 6-7 points in women) had a 34% lower hazard of death (95% CI: 0.59, 0.75) compared with participants within the lowest category of the WCRF/AICR score (0-2 points in men; 0-3 points in women). Significant inverse associations were observed in all countries. The WCRF/AICR score was also significantly associated with a lower hazard of dying from cancer, circulatory disease, and respiratory disease. CONCLUSION: Results of this study suggest that following WCRF/AICR recommendations could significantly increase longevity.",
"title": "Adherence to the World Cancer Research Fund/American Institute for Cancer Research guidelines and risk of death in Europe: results from the Europea..."
},
{
"docid": "MED-2378",
"text": "Background Polyunsaturated fatty acids (PUFA) have beneficial effects on cardiovascular risk, although the mechanisms are incompletely understood. In a previous article, we showed significant reductions in low-density lipoprotein cholesterol and several markers of inflammation with increasing intake of alpha-linolenic acid (ALA) from walnuts and flax. Objective To examine effects of ALA on cardiovascular responses to acute stress, flow-mediated dilation (FMD) of the brachial artery, and blood concentrations of endothelin-1 and arginine-vasopressin (AVP). Design Using a randomized, crossover study design, cardiovascular responses to acute stress were assessed in 20 hypercholesterolemic subjects, a subset of whom also underwent FMD testing (n = 12). Participants were fed an average American diet (AAD) and 2 experimental diets that varied in the amount of ALA and linoleic acid (LA) that they contained. The AAD provided 8.7% energy from PUFA (7.7% LA, 0.8% ALA). On the LA diet, saturated fat was reduced, and PUFA from walnuts and walnut oil provided 16.4% of energy (12.6% LA, 3.6% ALA). On the ALA diet, walnuts, walnut oil, and flax oil provided 17% energy from PUFA (10.5% LA, 6.5% ALA). Results The ALA and LA diets significantly reduced diastolic blood pressure (−2 to −3 mm Hg) and total peripheral resistance (−4%), and this effect was evident at rest and during stress (main effect of diet, p < 0.02). FMD increased (+34%) on the diet containing additional ALA. AVP also increased by 20%, and endothelin-1 was unchanged. Conclusions These results suggest novel mechanisms for the cardioprotective effects of walnuts and flax, and further work is needed to identify the bioactives responsible for these effects.",
"title": "Effects of Diets High in Walnuts and Flax Oil on Hemodynamic Responses to Stress and Vascular Endothelial Function"
},
{
"docid": "MED-2528",
"text": "OBJECTIVE: To describe changes in negative emotions among participants of a cholesterol-lowering study. DESIGN: Cohort study. Quantitative evaluation of changes in negative emotions in relation to diet and plasma cholesterol levels before and after a 5-year dietary intervention program aimed at reducing plasma cholesterol levels. SETTING: Community-dwelling families of the Family Heart Study, Portland, Oregon. PARTICIPANTS: One hundred forty-nine men and 156 women from 233 families (mean age, 37.7 years). MEASUREMENTS: Changes in negative emotions including depression and aggressive hostility as measured by the Hopkins Symptom Checklist (SCL-90). RESULTS: Improvement in overall emotional state was noted for the entire sample. Those who consumed a low-fat, high complex-carbohydrate diet at the end of the study showed significantly greater improvements in depression (P = 0.044; difference in improvement, 2.9 points) and aggressive hostility (P = 0.035; difference in improvement, 3.3 points) as well as a reduction in their plasma cholesterol levels (P = 0.024; difference in improvement, 2.7%) compared with those who ate a high-fat \"American diet.\" CONCLUSIONS: Participation in a cholesterol-lowering program may not be associated with a worsening in emotional state. To the contrary, improvements in diet appear to be associated with reductions in depression and aggressive hostility as well as with lowered plasma cholesterol levels.",
"title": "Improvements in hostility and depression in relation to dietary change and cholesterol lowering. The Family Heart Study."
},
{
"docid": "MED-1333",
"text": "New epidemiology confirms that glucose intolerance is a risk factor for pancreatic cancer, and that this association cannot be accounted for by an adverse impact of early pancreatic cancer on beta cell function. Previous reports indicate that risk for pancreatic cancer is increased in adult-onset diabetics. Since streptozotocin diabetes inhibits carcinogen-mediated induction of pancreatic cancer in hamsters, the most reasonable interpretation of these findings is that insulin (or some other beta cell product) acts as a promoter for pancreatic carcinogenesis. This view is consistent with a report that human pancreatic adenocarcinomas express insulin receptors that can stimulate mitosis; an additional possibility is that high insulin levels indirectly promote pancreatic carcinogenesis by boosting effective IGF-I activity via hepatic actions. In international ecologic epidemiology, pancreatic cancer rates correlate tightly with dietary intake of animal products; this may reflect the fact that vegan diets are associated with low diurnal insulin secretion. There is also suggestive evidence that macrobiotic vegan diets, which are low in glycemic index, may increase mean survival time in pancreatic cancer. However, other types of diets associated with decreased postprandial insulin response, such as high-protein diets or 'Mediterranean' diets high in oleic acid, may also have the potential for pancreatic cancer prevention. The huge increases of age-adjusted pancreatic cancer mortality in Japan and among African-Americans during the last century imply that pancreatic cancer is substantially preventable; a low-insulin-response diet coupled with exercise training, weight control, and smoking avoidance, commendable for a great many other reasons, may slash pancreatic cancer mortality dramatically. Copyright 2001 Harcourt Publishers Ltd.",
"title": "Insulin secretion as a determinant of pancreatic cancer risk."
}
] |
PLAIN-2926
|
Americans Are Living Longer but Sicker Lives
|
[
{
"docid": "MED-4847",
"text": "Clinical experience suggests that fasting followed by vegetarian diet may help patients with rheumatoid arthritis (RA). We reviewed the available scientific evidence, because patients frequently ask for dietary advice, and exclusive pharmacological treatment of RA is often not satisfying. Fasting studies in RA were searched in MEDLINE and by checking references in relevant reports. The results of the controlled studies which reported follow-up data for at least three months after fasting were quantitatively pooled. Thirty-one reports of fasting studies in patients with RA were found. Only four controlled studies investigated the effects of fasting and subsequent diets for at least three months. The pooling of these studies showed a statistically and clinically significant beneficial long-term effect. Thus, available evidence suggests that fasting followed by vegetarian diets might be useful in the treatment of RA. More randomised long-term studies are needed to confirm this view by methodologically convincing data.",
"title": "Fasting followed by vegetarian diet in patients with rheumatoid arthritis: a systematic review."
},
{
"docid": "MED-4846",
"text": "The effects of a strict uncooked vegan diet on serum lipid and sterol concentrations were studied in patients with rheumatoid arthritis. The subjects were randomized into a vegan diet group (n 16), who consumed a vegan diet for 2-3 months, or into a control group (n 13), who continued their usual omnivorous diets. Serum total and LDL-cholesterol and -phospholipid concentrations were significantly decreased by the vegan diet. The levels of serum cholestanol and lathosterol also decreased, but serum cholestanol:total cholesterol and lathosterol:total cholesterol did not change. The effect of a vegan diet on serum plant sterols was divergent as the concentration of campesterol decreased while that of sitosterol increased. This effect resulted in a significantly greater sitosterol:campesterol value in the vegan diet group than in the control group (1.48 (SD 0.39) v. 0.72 (SD 0.14); P < 0.001). A higher concentration of campesterol compared with sitosterol is normal in omnivorous subjects and can be explained by lower absorption and esterification rates of sitosterol. Our results suggest that a strict uncooked vegan diet changes the relative absorption rates of these sterols and/or their biliary clearance.",
"title": "Divergent changes in serum sterols during a strict uncooked vegan diet in patients with rheumatoid arthritis."
},
{
"docid": "MED-4849",
"text": "We tested the effects of an uncooked vegan diet, rich in lactobacilli, in rheumatoid patients randomized into diet and control groups. The intervention group experienced subjective relief of rheumatic symptoms during intervention. A return to an omnivorous diet aggravated symptoms. Half of the patients experienced adverse effects (nausea, diarrhoea) during the diet and stopped the experiment prematurely. Indicators of rheumatic disease activity did not differ statistically between groups. The positive subjective effect experienced by the patients was not discernible in the more objective measures of disease activity (Health Assessment Questionnaire, duration of morning stiffness, pain at rest and pain on movement). However, a composite index showed a higher number of patients with 3-5 improved disease activity measures in the intervention group. Stepwise regression analysis associated a decrease in the disease activity (measured as change in the Disease Activity Score, DAS) with lactobacilli-rich and chlorophyll-rich drinks, increase in fibre intake, and no need for gold, methotrexate or steroid medication (R2=0.48, P=0.02). The results showed that an uncooked vegan diet, rich in lactobacilli, decreased subjective symptoms of rheumatoid arthritis. Large amounts of living lactobacilli consumed daily may also have positive effects on objective measures of rheumatoid arthritis.",
"title": "Uncooked, lactobacilli-rich, vegan food and rheumatoid arthritis."
},
{
"docid": "MED-4853",
"text": "OBJECTIVE: To demonstrate the effects of a very low-fat, vegan diet on patients with rheumatoid arthritis (RA). DESIGN: Single-blind dietary intervention study. SUBJECTS AND STUDY INTERVENTIONS: This study evaluated the influence of a 4-week, very low-fat (approximately 10%), vegan diet on 24 free-living subjects with RA, average age, 56 +/- 11 years old. OUTCOME MEASUREMENTS: Prestudy and poststudy assessment of RA symptomatology was performed by a rheumatologist blind to the study design. Biochemical measures and 4-day diet data were also collected. Subjects met weekly for diet instruction, compliance monitoring, and progress assessments. RESULTS: There were significant (p < 0.001) decreases in fat (69%), protein (24%), and energy (22%), and a significant increase in carbohydrate (55%) intake. All measures of RA symptomatology decreased significantly (p < 0.05), except for duration of morning stiffness (p > 0.05). Weight also decreased significantly (p < 0.001). At 4 weeks, C-reactive protein decreased 16% (ns, p > 0.05), RA factor decreased 10% (ns, p > 0.05), while erythrocyte sedimentation rate was unchanged (p > 0.05). CONCLUSION: This study showed that patients with moderate-to-severe RA, who switch to a very low-fat, vegan diet can experience significant reductions in RA symptoms.",
"title": "Effects of a very low-fat, vegan diet in subjects with rheumatoid arthritis."
},
{
"docid": "MED-4854",
"text": "In a controlled clinical trial we have recently shown that patients with rheumatoid arthritis (RA) improved after fasting for 7-10 d and that the improvement could be sustained through 3.5 months with a vegan diet and 9 months with a lactovegetarian diet. Other studies have indicated that the inflammatory process in RA can be reduced through manipulation of dietary fatty acids. A switch to a vegetarian diet significantly alters the intake of fatty acids. Therefore, we have analysed the changes in fatty acid profiles of the plasma phospholipid fraction and related these changes to disease activity. The concentrations of the fatty acids 20:3n-6 and 20:4n-6 were significantly reduced after 3.5 months with a vegan diet (P < 0.0001 and P < 0.01 respectively), but the concentration increased to baseline values with a lactovegetarian diet. The concentration of 20:5n-3 was significantly reduced after the vegan diet (P < 0.0001) and the lactovegetarian diet periods (P < 0.01). There was no significant difference in fatty acid concentrations between diet responders and diet non-responders after the vegan or lactovegetarian diet periods. Our results indicate that the changes in the fatty acid profiles cannot explain the clinical improvement.",
"title": "Changes in plasma phospholipid fatty acids and their relationship to disease activity in rheumatoid arthritis patients treated with a vegetarian diet."
},
{
"docid": "MED-4845",
"text": "Fasting is an effective treatment for rheumatoid arthritis, but most patients relapse on reintroduction of food. The effect of fasting followed by one year of a vegetarian diet was assessed in a randomised, single-blind controlled trial. 27 patients were allocated to a four-week stay at a health farm. After an initial 7-10 day subtotal fast, they were put on an individually adjusted gluten-free vegan diet for 3.5 months. The food was then gradually changed to a lactovegetarian diet for the remainder of the study. A control group of 26 patients stayed for four weeks at a convalescent home, but ate an ordinary diet throughout the whole study period. After four weeks at the health farm the diet group showed a significant improvement in number of tender joints, Ritchie's articular index, number of swollen joints, pain score, duration of morning stiffness, grip strength, erythrocyte sedimentation rate, C-reactive protein, white blood cell count, and a health assessment questionnaire score. In the control group, only pain score improved score. In the control group, only pain score improved significantly. The benefits in the diet group were still present after one year, and evaluation of the whole course showed significant advantages for the diet group in all measured indices. This dietary regimen seems to be a useful supplement to conventional medical treatment of rheumatoid arthritis.",
"title": "Controlled trial of fasting and one-year vegetarian diet in rheumatoid arthritis."
},
{
"docid": "MED-4984",
"text": "Vegetarian and vegan diets offer significant benefits for diabetes management. In observational studies, individuals following vegetarian diets are about half as likely to develop diabetes, compared with non-vegetarians. In clinical trials in individuals with type 2 diabetes, low-fat vegan diets improve glycemic control to a greater extent than conventional diabetes diets. Although this effect is primarily attributable to greater weight loss, evidence also suggests that reduced intake of saturated fats and high-glycemic-index foods, increased intake of dietary fiber and vegetable protein, reduced intramyocellular lipid concentrations, and decreased iron stores mediate the influence of plant-based diets on glycemia. Vegetarian and vegan diets also improve plasma lipid concentrations and have been shown to reverse atherosclerosis progression. In clinical studies, the reported acceptability of vegetarian and vegan diets is comparable to other therapeutic regimens. The presently available literature indicates that vegetarian and vegan diets present potential advantages for the management of type 2 diabetes.",
"title": "Vegetarian and vegan diets in type 2 diabetes management."
},
{
"docid": "MED-4843",
"text": "We have previously reported that significant improvement may be obtained in rheumatoid arthritis patients by fasting followed by a vegetarian diet for one year. The present study was carried out to examine to what extent biochemical and immunological variables changed during the clinical trial of fasting and vegetarian diet. For the patients who were randomised to the vegetarian diet there was a significant decrease in platelet count, leukocyte count, calprotectin, total IgG, IgM rheumatoid factor (RF), C3-activation products, and the complement components C3 and C4 after one month of treatment. None of the measured parameters changed significantly during this period in the group of omnivores. The course of 14 of 15 measured variables favored the vegetarians compared with the omnivores, but the difference was only significant for leukocyte count, IgM RF, and the complement components C3 and C4. Most of the laboratory variables declined considerably in the vegetarians who improved according to clinical variables, indicating a substantial reduction in inflammatory activity. The leukocyte count, however, decreased in the vegetarians irrespective of the clinical results. Thus, the decline in leukocyte count may be attributed to vegetarian diet per se and not to the reduction in disease activity. The results of the present study are in accordance with the findings from the clinical trial, namely that dietary treatment can reduce the disease activity in some patients with rheumatoid arthritis.",
"title": "Changes in laboratory variables in rheumatoid arthritis patients during a trial of fasting and one-year vegetarian diet."
},
{
"docid": "MED-4985",
"text": "Background: Low-fat vegetarian and vegan diets are associated with weight loss, increased insulin sensitivity, and improved cardiovascular health. Objective: We compared the effects of a low-fat vegan diet and conventional diabetes diet recommendations on glycemia, weight, and plasma lipids. Design: Free-living individuals with type 2 diabetes were randomly assigned to a low-fat vegan diet (n = 49) or a diet following 2003 American Diabetes Association guidelines (conventional, n = 50) for 74 wk. Glycated hemoglobin (Hb A1c) and plasma lipids were assessed at weeks 0, 11, 22, 35, 48, 61, and 74. Weight was measured at weeks 0, 22, and 74. Results: Weight loss was significant within each diet group but not significantly different between groups (−4.4 kg in the vegan group and −3.0 kg in the conventional diet group, P = 0.25) and related significantly to Hb A1c changes (r = 0.50, P = 0.001). Hb A1c changes from baseline to 74 wk or last available values were −0.34 and −0.14 for vegan and conventional diets, respectively (P = 0.43). Hb A1c changes from baseline to last available value or last value before any medication adjustment were −0.40 and 0.01 for vegan and conventional diets, respectively (P = 0.03). In analyses before alterations in lipid-lowering medications, total cholesterol decreased by 20.4 and 6.8 mg/dL in the vegan and conventional diet groups, respectively (P = 0.01); LDL cholesterol decreased by 13.5 and 3.4 mg/dL in the vegan and conventional groups, respectively (P = 0.03). Conclusions: Both diets were associated with sustained reductions in weight and plasma lipid concentrations. In an analysis controlling for medication changes, a low-fat vegan diet appeared to improve glycemia and plasma lipids more than did conventional diabetes diet recommendations. Whether the observed differences provide clinical benefit for the macro- or microvascular complications of diabetes remains to be established. This trial was registered at clinicaltrials.gov as NCT00276939.",
"title": "A low-fat vegan diet and a conventional diabetes diet in the treatment of type 2 diabetes: a randomized, controlled, 74-wk clinical trial"
},
{
"docid": "MED-4879",
"text": "To estimate age using DNA based on telomere shortening, we determined the terminal restriction fragment (TRF) length, as telomere length, using Southern blot analysis of peripheral human blood and blood stains. All blood stains had been stored at room temperature for 5 months. The average TRF length clearly showed a tendency to shortening with aging. The formula for age estimation was based on a correlation between average TRF length and age of the subjects. The estimated age calculated from TRF length widely depends on environmental and genetic factors. However, as long as the DNA is well preserved, use of our method is feasible regardless of age of the subject and can give a rough estimation of age of subjects in forensic samples that carry no morphological information. Copyright 2002 Elsevier Science Ireland Ltd.",
"title": "Estimating age of humans based on telomere shortening."
},
{
"docid": "MED-4987",
"text": "BACKGROUND: Cardiovascular disease is the leading cause of mortality among adults with Type 2 diabetes. The thiazolidinediones including rosiglitazone are approved for the treatment of Type 2 diabetes on the basis of their ability to lower blood sugar and surrogate markers of cardiovascular disease. OBJECTIVES: To ascertain the cardiovascular, skeletal and hematologic safety profile of rosiglitazone. METHODS: Synthesis of evidence from recent trials, systematic reviews, meta-analysis, regulatory documents and clinical trials registries of manufacturers. CONCLUSION: Rosiglitazone increases the risk of heart failure, myocardial infarction and fractures (in women) with Type 2 diabetes.",
"title": "The safety of rosiglitazone in the treatment of type 2 diabetes."
},
{
"docid": "MED-4852",
"text": "OBJECTIVES: A dietary link to rheumatoid arthritis (RA) has been suspected and an influence on arthritic symptoms by different diets has been reported. Our primary aim was to record the self-experienced adverse food reactions in patients with RA. A secondary aim was to relate self-experienced adverse reactions to dairy produce and wheat to the local mucosal reactivity observed after rectal challenge with cow's milk protein (CM) and wheat gluten. METHODS: A questionnaire about self-experienced adverse reaction to food was sent to 347 RA patients. Rectal challenge with CM and gluten was performed in 27 of these patients and in healthy controls (n = 18). After a 15-h challenge the mucosal production of nitric oxide (NO) and the mucosal release of myeloperoxidase (MPO) and eosinophil cationic protein (ECP) were measured by using the mucosal patch technique. RESULTS: Twenty-seven per cent of the RA patients reported food intolerance (FI) to various foods, and in particular to CM, meat, and wheat gluten. Strong mucosal reactivity to CM was observed in 11% of the patients. Moderately increased mucosal reactivity to CM and gluten was found in 22% and 33%, respectively, of the patients. No relationship was found between self-experienced adverse reactions to CM or gluten and mucosal reactivity to these proteins. CONCLUSIONS: Perceived FI is reported frequently by RA patients, with a prevalence similar to that reported previously in the general population. Mucosal reactivity to CM and gluten is seen in a minor fraction of RA patients and is not related to the frequently perceived intolerance to these proteins.",
"title": "Self-reported food intolerance and mucosal reactivity after rectal food protein challenge in patients with rheumatoid arthritis."
},
{
"docid": "MED-4844",
"text": "Rheumatoid arthritis (RA) is characterized by inflammation of the synovial tissues in the joints. A number of papers related to dietary components that are associated with this inflammation are reviewed. In addition, the ecological approach is used to study the links between diet and RA. Multi-country data for prevalence of RA for females from eight and fifteen countries were compared statistically with components of national dietary supply. Fat from meat and offal for the period 2 years before the prevalence data was found to have the highest statistical association with the prevalence of RA (r(2) 0.877, P<0.001 for eight countries). The statistical correlations for meat and offal were almost as high as those for their fat. Similar correlations were found for temporal changes in indices of effects of RA in several European countries between 1968 and 1978 as more meat was added to the national diets, although the correlations were higher for meat than for fat. It is hypothesized that meat and offal may be a major factor contributing to the inflammation in RA. In the present short review, the author examines some of the data that associate meat consumption with RA and the possible factors, e.g. fat, Fe and nitrite, which may contribute to the inflammation.",
"title": "The role of meat in the expression of rheumatoid arthritis."
},
{
"docid": "MED-4848",
"text": "We have previously reported that a significant improvement can be obtained in rheumatoid arthritis patients by fasting followed by an individually adjusted vegetarian diet for one year. The patients who changed their diet could be divided into diet responders and diet nonresponders. After the clinical trial the patients were free to change diet or medication and after approximately one year they were asked to attend a new clinical examination. We compared the change from baseline (i.e. at the time of study entry) to the time of the follow-up examination for diet responders, diet nonresponders and controls who ate an omnivorous diet. The following variables favoured diet responders: pain score, duration of morning stiffness, Stanford Health Assessment Questionnaire index, number of tender joints, Ritchie's articular index, number of swollen joints, ESR and platelet count [corrected]. The difference between the three groups were significant for all the clinical variables, except for grip strength. There was no significant difference between the groups with regard to laboratory or anthropometric variables. At the time of the follow-up examination all diet responders but only half of the diet nonresponders still followed a diet. Our findings indicate that a group of patients with rheumatoid arthritis benefit from dietary manipulations and that the improvement can be sustained through a two-year period.",
"title": "Vegetarian diet for patients with rheumatoid arthritis--status: two years after introduction of the diet."
},
{
"docid": "MED-4851",
"text": "The notion that dietary factors may influence rheumatoid arthritis (RA) has been a part of the folklore of the disease, but scientific support for this has been sparse. In a controlled, single-blind trial we tested the effect of fasting for 7-10 d, then consuming an individually adjusted, gluten-free, vegan diet for 3.5 mo, and then consuming an individually adjusted lactovegetarian diet for 9 mo on patients with RA. For all clinical variables and most laboratory variables measured, the 27 patients in the fasting and vegetarian diet groups improved significantly compared with the 26 patients in the control group who followed their usual omnivorous diet throughout the study period. One year after the patients completed the trial, they were reexamined. Compared with baseline, the improvements measured were significantly greater in the vegetarians who previously benefited from the diet (diet responders) than in diet nonresponders and omnivores. The beneficial effect could not be explained by patients' psychologic characteristics, antibody activity against food antigens, or changes in concentrations of prostaglandin and leukotriene precursors. However, the fecal flora differed significantly between samples collected at time points at which there was substantial clinical improvement and time points at which there were no or only minor improvements. In summary, the results show that some patients with RA can benefit from a fasting period followed by a vegetarian diet. Thus, dietary treatment may be a valuable adjunct to the ordinary therapeutic armamentarium for RA.",
"title": "Rheumatoid arthritis treated with vegetarian diets."
},
{
"docid": "MED-4988",
"text": "OBJECTIVE We assessed the prevalence of type 2 diabetes in people following different types of vegetarian diets compared with that in nonvegetarians. RESEARCH DESIGN AND METHODS The study population comprised 22,434 men and 38,469 women who participated in the Adventist Health Study-2 conducted in 2002–2006. We collected self-reported demographic, anthropometric, medical history, and lifestyle data from Seventh-Day Adventist church members across North America. The type of vegetarian diet was categorized based on a food-frequency questionnaire. We calculated odds ratios (ORs) and 95% CIs using multivariate-adjusted logistic regression. RESULTS Mean BMI was lowest in vegans (23.6 kg/m2) and incrementally higher in lacto-ovo vegetarians (25.7 kg/m2), pesco-vegetarians (26.3 kg/m2), semi-vegetarians (27.3 kg/m2), and nonvegetarians (28.8 kg/m2). Prevalence of type 2 diabetes increased from 2.9% in vegans to 7.6% in nonvegetarians; the prevalence was intermediate in participants consuming lacto-ovo (3.2%), pesco (4.8%), or semi-vegetarian (6.1%) diets. After adjustment for age, sex, ethnicity, education, income, physical activity, television watching, sleep habits, alcohol use, and BMI, vegans (OR 0.51 [95% CI 0.40–0.66]), lacto-ovo vegetarians (0.54 [0.49–0.60]), pesco-vegetarians (0.70 [0.61–0.80]), and semi-vegetarians (0.76 [0.65–0.90]) had a lower risk of type 2 diabetes than nonvegetarians. CONCLUSIONS The 5-unit BMI difference between vegans and nonvegetarians indicates a substantial potential of vegetarianism to protect against obesity. Increased conformity to vegetarian diets protected against risk of type 2 diabetes after lifestyle characteristics and BMI were taken into account. Pesco- and semi-vegetarian diets afforded intermediate protection.",
"title": "Type of Vegetarian Diet, Body Weight, and Prevalence of Type 2 Diabetes"
},
{
"docid": "MED-4850",
"text": "Plants are rich natural sources of antioxidants in addition to other nutrients. Interventions and cross sectional studies on subjects consuming uncooked vegan diet called living food (LF) have been carried out. We have clarified the efficacy of LF in rheumatoid diseases as an example of a health problem where inflammation is one of the main concerns. LF is an uncooked vegan diet and consists of berries, fruits, vegetables and roots, nuts, germinated seeds and sprouts, i.e. rich sources of carotenoids, vitamins C and E. The subjects eating LF showed highly increased levels of beta and alfa carotenes, lycopen and lutein in their sera. Also the increases of vitamin C and vitamin E (adjusted to cholesterol) were statistically significant. As the berry intake was 3-fold compared to controls the intake of polyphenolic compounds like quercetin, myricetin and kaempherol was much higher than in the omnivorous controls. The LF diet is rich in fibre, substrate of lignan production, and the urinary excretion of polyphenols like enterodiol and enterolactone as well as secoisolaricirecinol were much increased in subjects eating LF. The shift of fibromyalgic subjects to LF resulted in a decrease of their joint stiffness and pain as well as an improvement of their self-experienced health. The rheumatoid arthritis patients eating the LF diet also reported similar positive responses and the objective measures supported this finding. The improvement of rheumatoid arthritis was significantly correlated with the day-to-day fluctuation of subjective symptoms. In conclusion the rheumatoid patients subjectively benefited from the vegan diet rich in antioxidants, lactobacilli and fibre, and this was also seen in objective measures.",
"title": "Antioxidants in vegan diet and rheumatic disorders."
}
] |
[
{
"docid": "MED-2311",
"text": "BACKGROUND: The association between fruit and vegetable (FV) consumption and overall mortality has seldom been investigated in large cohort studies. Findings from the few available studies are inconsistent. OBJECTIVE: The objective was to examine the dose-response relation between FV consumption and mortality, in terms of both time and rate, in a large prospective cohort of Swedish men and women. DESIGN: FV consumption was assessed through a self-administrated questionnaire in a population-based cohort of 71,706 participants (38,221 men and 33,485 women) aged 45-83 y. We performed a dose-response analysis to evaluate 10th survival percentile differences (PDs) by using Laplace regression and estimated HRs by using Cox regression. RESULTS: During 13 y of follow-up, 11,439 deaths (6803 men and 4636 women) occurred in the cohort. In comparison with 5 servings FV/d, a lower consumption was progressively associated with shorter survival and higher mortality rates. Those who never consumed FV lived 3 y shorter (PD: -37 mo; 95% CI: -58, -16 mo) and had a 53% higher mortality rate (HR: 1.53; 95% CI: 1.19, 1.99) than did those who consumed 5 servings FV/d. Consideration of fruit and vegetables separately showed that those who never consumed fruit lived 19 mo shorter (PD: -19 mo; 95% CI: -29, -10 mo) than did those who ate 1 fruit/d. Participants who consumed 3 vegetables/d lived 32 mo longer than did those who never consumed vegetables (PD: 32 mo; 96% CI: 13, 51 mo). CONCLUSION: FV consumption <5 servings/d is associated with progressively shorter survival and higher mortality rates. The Swedish Mammography Cohort and the Cohort of Swedish Men were registered at clinicaltrials.gov as NCT01127698 and NCT01127711, respectively.",
"title": "Fruit and vegetable consumption and all-cause mortality: a dose-response analysis."
},
{
"docid": "MED-2519",
"text": "To date, the only intervention that has consistently been shown to slow the rate of aging, and to increase mean and maximum lifespan in short-lived species, is life-long calorie restriction. It is yet unclear whether long-term calorie restriction in longer lived species (i.e. primates and humans) will have a similar effect. In humans, several studies investigating short-term calorie restriction or \"weight loss\" programs suggest beneficial outcomes on parameters of cardiovascular disease. Studies on long-term calorie restriction are performed on a self-selected group of human subjects and show similar effects. However, few studies are currently investigating the quality of life and potential pitfalls of long-term calorie restriction in humans. It is likely that some of the physiological and psychological effects of caloric restriction that occur in animals may impact the human life very differently. For certain, calorie restriction has a plethora of health benefits in mammals, such as a reduction in age-related diseases such as cancer. However, despite the \"magic\" of CR, this intervention in humans may present itself with a number of health concerns, which may not be applicable to or impact the life of experimental animals, but may do so in humans. These potential pitfalls and \"side effects\" are not clearly addressed in the literature and will be a focus of this review.",
"title": "Caloric restriction in humans: potential pitfalls and health concerns."
},
{
"docid": "MED-1254",
"text": "OBJECTIVE: To investigate the effect of replacing lean meat with a soy product, tofu, on coronary heart disease risk factors including serum lipoproteins, lipoprotein (a), factor VII, fibrinogen and in vitro susceptibility of LDL to oxidation. DESIGN: A randomized cross over dietary intervention study. SETTING: Free-living individuals studied at Deakin University. SUBJECTS: Forty-five free-living healthy males aged 35 to 62 years completed the dietary intervention. Three subjects were non-compliant and excluded prior to analysis. INTERVENTIONS: A diet containing 150 grams of lean meat per day was compared to a diet containing 290 grams of tofu per day in an isocaloric and isoprotein substitution. Each dietary period was one month duration. RESULTS: Analysis of the seven-day diet record showed that diets were similar in energy, protein, carbohydrate, total fat, saturated and unsaturated fat, polyunsaturated to saturated fat ratio, alcohol and fiber. Total cholesterol and triglycerides were significantly lower, and in vitro LDL oxidation lag phase was significantly longer on the tofu diet compared to the meat diet. The hemostatic factors, factor VII and fibrinogen, and lipoprotein(a) were not significantly affected by the tofu diet. CONCLUSIONS: The increase in LDL oxidation lag phase would be expected to be associated with a decrease in coronary heart disease risk.",
"title": "Effect of meat replacement by tofu on CHD risk factors including copper induced LDL oxidation."
},
{
"docid": "MED-1376",
"text": "Background. There are places around the world where people live longer and they are active past the age of 100 years, sharing common behavioral characteristics; these places (i.e., Sardinia in Italy, Okinawa in Japan, Loma Linda in California and Nicoya Peninsula in Costa Rica) have been named the “Blue Zones”. Recently it was reported that people in Ikaria Island, Greece, have also one of the highest life expectancies in the world, and joined the “Blue Zones”. The aim of this work work was to evaluate various demographic, lifestyle and psychological characteristics of very old (>80 years) people participated in Ikaria Study. Methods. During 2009, 1420 people (aged 30+) men and women from Ikaria Island, Greece, were voluntarily enrolled in the study. For this work, 89 males and 98 females over the age of 80 yrs were studied (13% of the sample). Socio-demographic, clinical, psychological and lifestyle characteristics were assessed using standard questionnaires and procedures. Results. A large proportion of the Ikaria Study's sample was over the age of 80; moreover, the percent of people over 90 were much higher than the European population average. The majority of the oldest old participants reported daily physical activities, healthy eating habits, avoidance of smoking, frequent socializing, mid-day naps and extremely low rates of depression. Conclusion. Modifiable risk factors, such as physical activity, diet, smoking cessation and mid-day naps, might depict the “secrets” of the long-livers; these findings suggest that the interaction of environmental, behavioral together with clinical characteristics may determine longevity. This concept must be further explored in order to understand how these factors relate and which are the most important in shaping prolonged life.",
"title": "Sociodemographic and Lifestyle Statistics of Oldest Old People (>80 Years) Living in Ikaria Island: The Ikaria Study"
},
{
"docid": "MED-4708",
"text": "BACKGROUND/OBJECTIVES: Walnuts have been shown to reduce serum lipids in short-term well-controlled feeding trials. Little information exists on the effect and sustainability of walnut consumption for longer duration in a free-living situation. SUBJECTS/METHODS: A randomized crossover design in which 87 subjects with normal to moderate high plasma total cholesterol were initially assigned to a walnut-supplemented diet or habitual (control) diet for a 6-month period, then switched to the alternate dietary intervention for a second 6-month period. Each subject attended seven clinics 2 months apart. At each clinic, body weight was measured, and in five clinics (months 0, 4, 6, 10 and 12), a blood sample was collected. RESULTS: Our study showed that supplementing a habitual diet with walnuts (12% of total daily energy intake equivalent) improves the plasma lipid profile. This beneficial effect was more significant in subjects with high plasma total cholesterol at baseline. Significant changes in serum concentrations of total cholesterol (P=0.02) and triglycerides (P=0.03) were seen and nearly significant changes in low-density lipoprotein cholesterol (LDL-C) (P=0.06) were found. No significant change was detected in either high-density lipoprotein (HDL) cholesterol LDL to HDL ratio. CONCLUSIONS: Including walnuts as part of a habitual diet favorably altered the plasma lipid profile. The lipid-lowering effects of walnuts were more evident among subjects with higher lipid baseline values, precisely those people with greater need of reducing plasma total and LDL-C.",
"title": "Long-term walnut supplementation without dietary advice induces favorable serum lipid changes in free-living individuals."
},
{
"docid": "MED-3692",
"text": "Probiotics are live microorganisms that confer a health benefit on the host when administered in appropriate amounts. Over 700 randomized, controlled, human studies have been conducted with probiotics thus far, with the results providing strong support for the use of probiotics in the clinical prevention or treatment of gastrointestinal tract disorders and metabolic syndrome. The present review is based on webinar presentations that were developed by the American Gastroenterological Association (AGA) in partnership with the International Scientific Association for Probiotics and Prebiotics (ISAPP) and the North American branch of the International Life Sciences Institute (ILSI North America). The presentations provided gastroenterologists and researchers with fundamental and current scientific information on the influence of gut microbiota on human health and disease, as well as clinical intervention strategies and practical guidelines for the use of probiotics and prebiotics. © 2011 International Life Sciences Institute.",
"title": "Human gut microbiota and its relationship to health and disease."
},
{
"docid": "MED-5042",
"text": "The Kuna Indians who reside in an archipelago on the Caribbean Coast of Panama have very low blood pressure levels, live longer than other Panamanians, and have a reduced frequency of myocardial infarction, stroke, diabetes mellitus, and cancer -- at least on their death certificates. One outstanding feature of their diet includes a very high intake of flavanol-rich cocoa. Flavonoids in cocoa activate nitric oxide synthesis in healthy humans. The possibility that the high flavanol intake protects the Kuna against high blood pressure, ischemic heart disease, stroke, diabetes mellitus, and cancer is sufficiently intriguing and sufficiently important that large, randomized controlled clinical trials should be pursued.",
"title": "Flavanols, the Kuna, Cocoa Consumption, and Nitric Oxide"
},
{
"docid": "MED-3944",
"text": "Dietary interventions involving antioxidants are of interest for reducing inflammation, improving joint motion, and altering pain perception. We evaluated the effect of oral consumption of a fruit and berry blend on pain and range of motion (ROM). This open-label clinical pilot study involved 14 study participants with limitations in ROM that was associated with pain and affected daily living. Participants included but were not limited to those with age-related osteoarthritis. Study participants consumed 120 mL MonaVie Active® fruit juice, predominantly containing açai pulp (Euterpe oleracea Mart.) and other fruit concentrates, daily for 12 weeks. Study participants were assessed at baseline and 2, 4, 8, and 12 weeks by structured nurse interviews, pain and activities of daily living (ADL) questionnaires, blood samples, and ROM assessment. Pain was scored by using a visual analogue scale. ROM was assessed by using dual digital inclinometry as recommended by American Medical Association guidelines. Consumption of the juice resulted in significant pain reduction, improved ROM measures, and improvement in ADLs. Serum antioxidant status, as monitored by the cell-based antioxidant protection in erythrocytes (CAP-e) assay, was improved within 2 weeks and continued to improve throughout the 12 weeks of study participation (P<.01). The inflammatory marker C-reactive protein was reduced at 12 weeks, but this change did not reach statistical significance. Lipid peroxidation decreased mildly at 12 weeks. The antioxidant status, as measured by the CAP-e bioassay, showed the best correlation with improvements in physical well-being (pain, ROM, and ADL). The significant association among increased antioxidant status, improved ROM, and pain reduction warrants further study.",
"title": "Pain Reduction and Improvement in Range of Motion After Daily Consumption of an Açai (Euterpe oleracea Mart.) Pulp–Fortified Polyphenolic-Rich Fruit and Berry Juice Blend"
},
{
"docid": "MED-4783",
"text": "INTRODUCTION: Historically, breast cancer incidence has been substantially higher in the United States than in Asia. When Asian women migrate to the United States, their breast cancer risk increases over several generations and approaches that for U.S. Whites. Thus, modifiable factors, such as diet, may be responsible. METHODS: In this population-based case-control study of breast cancer among women of Chinese, Japanese, and Filipino descent, ages 20 to 55 years, and living in San Francisco-Oakland (California), Los Angeles (California) and Oahu (Hawaii), we interviewed 597 cases (70% of those eligible) and 966 controls (75%) about adolescent and adult diet and cultural practices. For subjects with mothers living in the United States (39% of participants), we interviewed mothers of 99 cases (43% of eligible) and 156 controls (40%) about the daughter's childhood exposures. Seventy-three percent of study participants were premenopausal at diagnosis. RESULTS: Comparing highest with lowest tertiles, the multivariate relative risks (95% confidence interval) for childhood, adolescent, and adult soy intake were 0.40 (0.18-0.83; P(trend) = 0.03), 0.80 (0.59-1.08; P(trend) = 0.12), and 0.76 (0.56-1.02; P(trend) = 0.04), respectively. Inverse associations with childhood intake were noted in all three races, all three study sites, and women born in Asia and the United States. Adjustment for measures of westernization attenuated the associations with adolescent and adult soy intake but did not affect the inverse relationship with childhood soy intake. DISCUSSION: Soy intake during childhood, adolescence, and adult life was associated with decreased breast cancer risk, with the strongest, most consistent effect for childhood intake. Soy may be a hormonally related, early-life exposure that influences breast cancer incidence.",
"title": "Childhood soy intake and breast cancer risk in Asian American women."
},
{
"docid": "MED-4698",
"text": "Females live longer than males. Work from our laboratory has shown that this may be due to the up-regulation of longevity-associated genes by estrogens. Estrogens bind to the estrogen receptors and subsequently activate the mitogen activated protein kinase and nuclear factor kappa B signalling pathways, resulting in an up-regulation of antioxidant enzymes. Estrogen administration, however, has serious undesirable effects and of course, cannot be administered to males because of its powerful feminizing effects. Thus, we tested the effect of genistein, a phytoestrogen of high nutritional importance whose structure is similar to estradiol, on the regulation of the expression of antioxidant, longevity-related genes and consequently on oxidant levels in mammary gland tumour cells in culture. Phytoestrogens mimic the protective effect of oestradiol using the same signalling pathway. The critical importance of up-regulating antioxidant genes, by hormonal and dietary manipulations, to increase longevity is discussed.",
"title": "Role of mitochondrial oxidative stress to explain the different longevity between genders: protective effect of estrogens."
},
{
"docid": "MED-2218",
"text": "OBJECTIVE: To determine prevalence of dementia and its subtypes in Japanese-American men and compare these findings with rates reported for populations in Japan and elsewhere. DESIGN AND SETTING: The Honolulu Heart Program is a prospective population-based study of cardiovascular disease established in 1965. Prevalence estimates were computed from cases identified at the 1991 to 1993 examination. Cognitive performance was assessed using standardized methods, instruments, and diagnostic criteria. PARTICIPANTS: Subjects were 3734 Japanese-American men (80% of surviving cohort) aged 71 through 93 years, living in the community or in institutions. MAIN OUTCOME MEASURES: Age-specific, age-standardized, and cohort prevalence estimates were computed for dementia (all cause) defined by 2 sets of diagnostic criteria and 4 levels of severity. Prevalence levels for Alzheimer disease and vascular dementia were also estimated. RESULTS: Dementia prevalence by Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised ranged from 2.1% in men aged 71 through 74 years to 33.4% in men aged 85 through 93 years. Age-standardized prevalence was 7.6%. Prevalence estimates for the cohort were 9.3% for dementia (all cause), 5.4% for Alzheimer disease (primary or contributing), and 4.2% for vascular dementia (primary or contributing). More than 1 possible cause was found in 26% of cases. The Alzheimer disease/vascular dementia ratio was 1.5 for cases attributed primarily to Alzheimer disease or vascular dementia. CONCLUSIONS: Prevalence of Alzheimer disease in older Japanese-American men in Hawaii appears to be higher than in Japan but similar to European-ancestry populations. Prevalence of vascular dementia appears to be slightly lower than in Japan, but higher than in European-ancestry populations. Further cross-national research with emphasis on standardized diagnostic methods is needed.",
"title": "Prevalence of dementia in older Japanese-American men in Hawaii: The Honolulu-Asia Aging Study."
},
{
"docid": "MED-4104",
"text": "BACKGROUND: Although vegan diets improve diabetes management, little is known about the nutrient profiles or diet quality of individuals with type 2 diabetes who adopt a vegan diet. OBJECTIVE: To assess the changes in nutrient intake and dietary quality among participants following a low-fat vegan diet or the 2003 American Diabetes Association dietary recommendations. DESIGN: A 22-week randomized, controlled clinical trial examining changes in nutrient intake and diet quality. SUBJECTS/SETTING: Participants with type 2 diabetes (n=99) in a free-living setting. RESEARCH DESIGN AND METHODS: Participants were randomly assigned to a low-fat vegan diet or a 2003 American Diabetes Association recommended diet. MAIN OUTCOME MEASURES: Nutrient intake and Alternate Healthy Eating Index (AHEI) scores were collected at baseline and 22 weeks. STATISTICAL ANALYSES PERFORMED: Between-group t tests were calculated for changes between groups and paired comparison t tests were calculated for changes within-group. Pearson's correlation assessed relationship of AHEI score to hemoglobin A1c and body weight changes. RESULTS: Both groups reported significant decreases in energy, protein, fat, cholesterol, vitamin D, selenium, and sodium intakes. The vegan group also significantly reduced reported intakes of vitamin B-12 and calcium, and significantly increased carbohydrate, fiber, total vitamin A activity, beta carotene, vitamins K and C, folate, magnesium, and potassium. The American Diabetes Association recommended diet group also reported significant decreases in carbohydrate and iron, but reported no significant increases. The vegan group significantly improved its AHEI score (P<0.0001), while the American Diabetes Association recommended diet group did not (P=0.7218). The difference in AHEI score at 22 weeks between groups was significant (P<0.0001). With both groups combined, AHEI score was negatively correlated with both changes in hemoglobin A1c value (r=-0.24, P=0.016) and weight (r=-0.27, P=0.007). CONCLUSIONS: Vegan diets increase intakes of carbohydrate, fiber, and several micronutrients, in contrast with the American Diabetes Association recommended diet. The vegan group improved its AHEI score whereas the American Diabetes Association recommended diet group's AHEI score remained unchanged.",
"title": "Changes in nutrient intake and dietary quality among participants with type 2 diabetes following a low-fat vegan diet or a conventional diabetes di..."
},
{
"docid": "MED-2913",
"text": "The elimination kinetics of polychlorinated biphenyls (PCBs) in humans is difficult to assess in observational studies, because PCB exposure is never completely abolished. In a community with high dietary PCB exposures from whale blubber, we examined two groups of children with increased body burdens from breast-feeding. Follow-up was from ages 4.5 years to 7.5 years (99 subjects) and 7 to 14 years (101 subjects). The calculations were performed by the use of structural equation models, with adjustment for body weight and dietary blubber intake as the main source of postnatal exposure. As a likely result of background exposures, apparent elimination half-lives were unexpectedly long when based on results from all cohort members. Subjects with exposures above the median and in the highest quartile showed half-lives of about 3-4 years for CB-138, and 4.5-5.5 years for CB-105 and CB-118; 6.5-7.5 years for CB-156, CB-170, and CB-187; and 7-9 years for CB-153 and CB-180. The longest half-lives correspond to elimination of the parent PCB solely with a daily fat excretion rate of 1-2 g, while shorter half-lives assume metabolic break-down.",
"title": "Elimination Half-lives of Polychlorinated Biphenyl Congeners in Children"
},
{
"docid": "MED-2295",
"text": "BACKGROUND: Intake of dietary fiber has been recommended for many years as part of the guidelines from the American Heart Association, the Institute of Medicine, and other groups. The recommended Adequate Intake for dietary fiber for adults is 25 to 38 g/day (14 g/1,000 kcal/day). OBJECTIVE: To determine the average daily intake of dietary fiber among adults during the past decade and, specifically, to document progress toward national goals. DESIGN: Cross-sectional weighted data from the National Health and Nutrition Examination Survey among adults aged 18 years and older. PARTICIPANTS/SETTING: Data were collected from noninstitutionalized adults aged 18 years and older using a nationally representative, complex, multistage, probability-based survey of people living in the United States that was conducted by the National Center for Health Statistics. MAIN OUTCOME MEASURES: Daily dietary fiber intake by members of the US population based on 2-year groupings of the continuous survey from 1999 to 2008. RESULTS: Mean daily dietary fiber intake for 1999-2000 was 15.6 g/day, for 2001-2002 intake was 16.1g/day, for 2003-2004 intake was 15.5 g/day, for 2005-2006 intake was 15.8 g/day, and for 2007-2008 intake was 15.9 g/day. Participants with obesity (body mass index ≥30) consistently reported lower fiber intake than did individuals with normal weight or overweight (14.6 to 15.4 g/day and 15.6 to 16.8 g/day, respectively; P<0.0001). Mexican Americans had significantly higher intake in 1999-2000 than non-Hispanic whites (18.0 vs 16.1g/day; P<0.05), but Mexican Americans' intake did not increase over time (17.7 g/day in 2007-2008). Non-Hispanic blacks had fiber intake of 12.5 g/day at baseline that increased modestly to 13.1 g/day by 2007-2008. CONCLUSIONS: Daily fiber intake generally has not progressed toward national goals during the past decade, but there are some differences according to health and social factors. Additional clinical practice and public health strategies are needed. Copyright © 2012 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.",
"title": "Trends in dietary fiber intake in the United States, 1999-2008."
},
{
"docid": "MED-4440",
"text": "BACKGROUND: Contrary to earlier clinical studies suggesting that soy may promote breast tumor growth, two recent studies show that soy-containing foods are not adversely related to breast cancer prognosis. We examined, using data from the Women's Healthy Eating and Living (WHEL) study, the effect of soy intake on breast cancer prognosis. METHODS: Three thousand eighty-eight breast cancer survivors, diagnosed between 1991 and 2000 with early-stage breast cancer and participating in WHEL, were followed for a median of 7.3 years. Isoflavone intakes were measured postdiagnosis by using a food frequency questionnaire. Women self-reported new outcome events semiannually, which were then verified by medical records and/or death certificates. HRs and 95% CIs representing the association between either a second breast cancer event or death and soy intake were computed, adjusting for study group and other covariates, using the delayed entry Cox proportional hazards model. RESULTS: As isoflavone intake increased, risk of death decreased (P for trend = 0.02). Women at the highest levels of isoflavone intake (>16.3 mg isoflavones) had a nonsignificant 54% reduction in risk of death. CONCLUSION: Our study is the third epidemiologic study to report no adverse effects of soy foods on breast cancer prognosis. IMPACT: These studies, taken together, which vary in ethnic composition (two from the United States and one from China) and by level and type of soy consumption, provide the necessary epidemiologic evidence that clinicians no longer need to advise against soy consumption for women with a diagnosis of breast cancer. ©2011 AACR.",
"title": "Soy food consumption and breast cancer prognosis."
},
{
"docid": "MED-2645",
"text": "The development of the male reproductive ducts and external genitalia in vertebrates is dependent on elevated androgen concentrations during embryonic development and the period of postnatal growth. We have observed that a population of juvenile alligators living on Lake Apopka exhibit significantly smaller penis size (24% average decrease) and lower plasma concentrations of testosterone (70% lower concentrations) when compared to animals of similar size on Lake Woodruff. In addition to smaller phalli, no relationship exists between plasma testosterone concentrations and penile size in males from Lake Apopka, whereas a positive relationship exists for males from Lake Woodruff. The alligators on Lake Apopka are known to have elevated concentrations of the antiandrogenic DDT breakdown product p.p'-DDE stored in their fat. We suggest a number of hypotheses that could explain the modification in the phenotype of the juvenile male living in Lake Apopka. These modifications in phenotype include a smaller penis size, lower plasma androgen concentrations, and lack of responsiveness of the penis to the plasma androgens present.",
"title": "Reduction in penis size and plasma testosterone concentrations in juvenile alligators living in a contaminated environment."
},
{
"docid": "MED-4627",
"text": "The emerging role of chronic inflammation in the major degenerative diseases of modern society has stimulated research into the influence of nutrition and dietary patterns on inflammatory indices. Most human studies have correlated analyses of habitual dietary intake as determined by a food frequency questionnaire or 24-hour recall with systemic markers of inflammation like high-sensitivity C-reactive protein (HS-CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). An occasional study also includes nutrition analysis of blood components. There have been several controlled interventions which evaluated the effect of a change in dietary pattern or of single foods on inflammatory markers in defined populations. Most studies reveal a modest effect of dietary composition on some inflammatory markers in free-living adults, although different markers do not vary in unison. Significant dietary influences have been established for glycemic index (GI) and load (GL), fiber, fatty acid composition, magnesium, carotenoids, and flavonoids. A traditional Mediterranean dietary pattern, which typically has a high ratio of monounsaturated (MUFA) to saturated (SFA) fats and ω-3 to ω-6 polyunsaturated fatty acid (PUFAs) and supplies an abundance of fruits, vegetables, legumes, and grains, has shown anti-inflammatory effects when compared with typical North American and Northern European dietary patterns in most observational and interventional studies and may become the diet of choice for diminishing chronic inflammation in clinical practice.",
"title": "Diet and inflammation."
},
{
"docid": "MED-2000",
"text": "Background People with diabetes can suffer from diverse complications that seriously erode quality of life. Diabetes, costing the United States more than $174 billion per year in 2007, is expected to take an increasingly large financial toll in subsequent years. Accurate projections of diabetes burden are essential to policymakers planning for future health care needs and costs. Methods Using data on prediabetes and diabetes prevalence in the United States, forecasted incidence, and current US Census projections of mortality and migration, the authors constructed a series of dynamic models employing systems of difference equations to project the future burden of diabetes among US adults. A three-state model partitions the US population into no diabetes, undiagnosed diabetes, and diagnosed diabetes. A four-state model divides the state of \"no diabetes\" into high-risk (prediabetes) and low-risk (normal glucose) states. A five-state model incorporates an intervention designed to prevent or delay diabetes in adults at high risk. Results The authors project that annual diagnosed diabetes incidence (new cases) will increase from about 8 cases per 1,000 in 2008 to about 15 in 2050. Assuming low incidence and relatively high diabetes mortality, total diabetes prevalence (diagnosed and undiagnosed cases) is projected to increase from 14% in 2010 to 21% of the US adult population by 2050. However, if recent increases in diabetes incidence continue and diabetes mortality is relatively low, prevalence will increase to 33% by 2050. A middle-ground scenario projects a prevalence of 25% to 28% by 2050. Intervention can reduce, but not eliminate, increases in diabetes prevalence. Conclusions These projected increases are largely attributable to the aging of the US population, increasing numbers of members of higher-risk minority groups in the population, and people with diabetes living longer. Effective strategies will need to be undertaken to moderate the impact of these factors on national diabetes burden. Our analysis suggests that widespread implementation of reasonably effective preventive interventions focused on high-risk subgroups of the population can considerably reduce, but not eliminate, future increases in diabetes prevalence.",
"title": "Projection of the year 2050 burden of diabetes in the US adult population: dynamic modeling of incidence, mortality, and prediabetes prevalence"
},
{
"docid": "MED-4969",
"text": "Transmission of viruses, bacteria, and parasites to food by way of improperly washed hands is a major contributing factor in the spread of foodborne illnesses. Field observers have assessed compliance with hand washing regulations, yet few studies have included consideration of frequency and methods used by sectors of the food service industry or have included benchmarks for hand washing. Five 3-h observation periods of employee (n = 80) hand washing behaviors during menu production, service, and cleaning were conducted in 16 food service operations for a total of 240 h of direct observation. Four operations from each of four sectors of the retail food service industry participated in the study: assisted living for the elderly, childcare, restaurants, and schools. A validated observation form, based on 2005 Food Code guidelines, was used by two trained researchers. Researchers noted when hands should have been washed, when hands were washed, and how hands were washed. Overall compliance with Food Code recommendations for frequency during production, service, and cleaning phases ranged from 5% in restaurants to 33% in assisted living facilities. Procedural compliance rates also were low. Proposed benchmarks for the number of times hand washing should occur by each employee for each sector of food service during each phase of operation are seven times per hour for assisted living, nine times per hour for childcare, 29 times per hour for restaurants, and 11 times per hour for schools. These benchmarks are high, especially for restaurant employees. Implementation would mean lost productivity and potential for dermatitis; thus, active managerial control over work assignments is needed. These benchmarks can be used for training and to guide employee hand washing behaviors.",
"title": "Hand washing frequencies and procedures used in retail food services."
},
{
"docid": "MED-862",
"text": "Cutaneous synthesis of vitamin D by exposure to UVB is the principal source of vitamin D in the human body. Our current clothing habits and reduced time spent outdoors put us at risk of many insufficiency-related diseases that are associated with calcaemic and non-calcaemic functions of vitamin D. Populations with traditional lifestyles having lifelong, year-round exposure to tropical sunlight might provide us with information on optimal vitamin D status from an evolutionary perspective. We measured the sum of serum 25-hydroxyvitamin D₂ and D₃ (25(OH)D) concentrations of thirty-five pastoral Maasai (34 (SD 10) years, 43 % male) and twenty-five Hadzabe hunter-gatherers (35 (SD 12) years, 84 % male) living in Tanzania. They have skin type VI, have a moderate degree of clothing, spend the major part of the day outdoors, but avoid direct exposure to sunlight when possible. Their 25(OH)D concentrations were measured by liquid chromatography-MS/MS. The mean serum 25(OH)D concentrations of Maasai and Hadzabe were 119 (range 58-167) and 109 (range 71-171) nmol/l, respectively. These concentrations were not related to age, sex or BMI. People with traditional lifestyles, living in the cradle of mankind, have a mean circulating 25(OH)D concentration of 115 nmol/l. Whether this concentration is optimal under the conditions of the current Western lifestyle is uncertain, and should as a possible target be investigated with concomitant appreciation of other important factors in Ca homeostasis that we have changed since the agricultural revolution.",
"title": "Traditionally living populations in East Africa have a mean serum 25-hydroxyvitamin D concentration of 115 nmol/l."
},
{
"docid": "MED-3978",
"text": "SUMMARY The aim of this study was to investigate the relationship between dog and cat ownership and gastroenteritis in young children. A diary study of 965 children aged 4–6 years living in rural or semi-rural South Australia was undertaken. Data were collected on pet ownership, drinking water and other risk factors for gastroenteritis. Overall 89% of households had pets and dog ownership was more common than cat ownership. The multivariable models for gastroenteritis and pet ownership indicated that living in a household with a dog or cat was associated with a reduced risk of gastroenteritis (adj. OR 0·71, 95% CI 0·55–0·92; OR 0·70, % CI 0·51–0·97 respectively). This paper adds to the evidence that pets are not a major source of gastroenteritis in the home and lends support to the health benefits of pet ownership. However, this must be weighed against the potential negative consequences, such as dog bites, particularly for this age group.",
"title": "Does dog or cat ownership lead to increased gastroenteritis in young children in South Australia?"
},
{
"docid": "MED-4454",
"text": "The aim of this study was to determine the bioavailability and kinetics of the supposed anticarcinogen sulforaphane, the hydrolysis product of glucoraphanin, from raw and cooked broccoli. Eight men consumed 200 g of crushed broccoli, raw or cooked, with a warm meal in a randomized, free-living, open cross-over trial. Higher amounts of sulforaphane were found in the blood and urine when broccoli was eaten raw (bioavailability of 37%) versus cooked (3.4%, p ) 0.002). Absorption of sulforaphane was delayed when cooked broccoli was consumed (peak plasma time ) 6 h) versus raw broccoli (1.6 h, p ) 0.001). Excretion half-lives were comparable, 2.6 and 2.4 h on average, for raw and cooked broccoli, respectively (p ) 0.5). This study gives complete kinetic data and shows that consumption of raw broccoli results in faster absorption, higher bioavailability, and higher peak plasma amounts of sulforaphane, compared to cooked broccoli.",
"title": "Bioavailability and kinetics of sulforaphane in humans after consumption of cooked versus raw broccoli."
},
{
"docid": "MED-3305",
"text": "BACKGROUND AND AIM: The occurrence of malignant pleural mesothelioma (MPM) has been reported among population groups with no documented professional exposure to asbestos fibres living in different geographic areas. This paper reviews existing data related to non occupational MPM including its occurrence in the province of Catania (Sicily, Italy). METHODS: An electronic search of literature related to non occupational MPM was performed including the year 2005. RESULTS: Non occupational MPM in subjects living in areas contaminated by a variety of asbestos and non asbestos fibres has been well documented through a number of epidemiologic studies including cases series, case-control studies, and a cohort study. In addition, the observation of familial clustering of MPM, suggests that genetic factors may play a role in the pathogenesis of this malignancy. The epidemiological evidence also suggests that MPM may occur as a result of the interaction between environmental carcinogens, genetic factors, and virus infection. CONCLUSION: It is likely that genetic predisposition and non-occupational exposure to low doses of asbestos and asbestos-like fibres may concur to the development of malignant mesothelioma. However, additional epidemiological and laboratory studies are needed to further understand the relationship between environmental exposure and individual susceptibility to this malignancy.",
"title": "Non-occupational malignant pleural mesothelioma due to asbestos and non-asbestos fibres."
},
{
"docid": "MED-4180",
"text": "The aim was to determine half-life of six most abundant PCB congeners in the body of early adolescents. In 304 environmentally exposed children, PCB serum concentration was determined at the age of 8 and 12years. Half-life was determined for each child assuming exponential decrease or for the whole cohort using multiple regression. Results obtained by both approaches were in agreement. PCB reuptakes corrupting half-life estimates for each child and each congener were evaluated. If one of the serum PCB concentration values fell below the level of detection (LOD) the pair was excluded and if PCB half-life value exceeded the arbitrary value of 30years. The following median half-lives in years 4.46, 10.59, 9.7, 4.7, 9.1 and 9.8 were obtained for PCB congeners 118, 138(+163), 153, 156(+171), 170 and 180, respectively. The elimination half-life values were not systematically related to PCB serum concentration at any examination age. Between half-life values, percentage of children with significant reuptakes and PCB congener abundance in serum were found significant associations. Copyright © 2010 Elsevier Ltd. All rights reserved.",
"title": "Half-lives of serum PCB congener concentrations in environmentally exposed early adolescents."
},
{
"docid": "MED-3775",
"text": "We investigated the beneficial effects of drinking supplementary water during the school day on the cognitive performance and transitory subjective states, such as fatigue or vigor, in 168 children aged between 9 and 11years who were living in a hot climate (South Italy, Sardinia). The classes were randomly divided into an intervention group, which received water supplementation, and a control group. Dehydration was determined by urine sampling and was defined as urine osmolality greater than 800mOsm/kg H(2)O (Katz, Massry, Agomn, & Toor, 1965). The change in the scores from the morning to the afternoon of hydration levels, cognitive performance and transitory subjective states were correlated. In line with a previous observational study that evaluated the hydration status of school children living in a country with a hot climate (Bar-David, Urkin, & Kozminsky, 2005), our results showed that a remarkable proportion of children were in a state of mild, voluntary dehydration at the beginning of the school day (84%). We found a significant negative correlation between dehydration and the auditory number span, which indicates a beneficial effect of drinking supplementary water at school on short-term memory. Moreover, there was a positive correlation between dehydration and performance in the verbal analogy task. The results are discussed in the light of the complexity of the neurobiological mechanisms involved in the relationship between hydration status and cognition. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Effects of drinking supplementary water at school on cognitive performance in children."
},
{
"docid": "MED-4157",
"text": "Although improvement in long-term health is no longer an indication for menopausal hormone therapy, evidence supporting fewer adverse events in younger women, combined with its high overall effectiveness, has reinforced its usefulness for short-term treatment of menopausal symptoms. Menopausal therapy has been provided not only by commercially available products but also by compounding, or creation of an individualized preparation in response to a health care provider's prescription to create a medication tailored to the specialized needs of an individual patient. The Women's Health Initiative findings, coupled with an increase in the direct-to-consumer marketing and media promotion of compounded bioidentical hormonal preparations as safe and effective alternatives to conventional menopausal hormone therapy, have led to a recent increase in the popularity of compounded bioidentical hormones as well as an increase in questions about the use of these preparations. Not only is evidence lacking to support superiority claims of compounded bioidentical hormones over conventional menopausal hormone therapy, but these claims also pose the additional risks of variable purity and potency and lack efficacy and safety data. The Committee on Gynecologic Practice of the American College of Obstetricians and Gynecologists and the Practice Committee of the American Society for Reproductive Medicine provide an overview of the major issues of concern surrounding compounded bioidentical menopausal hormone therapy and provide recommendations for patient counseling. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.",
"title": "Compounded bioidentical menopausal hormone therapy."
},
{
"docid": "MED-3021",
"text": "The hair-to-blood ratio and biological half-life of methylmercury in a one-compartment model seem to differ between past and recent studies. To reevaluate them, 27 healthy volunteers were exposed to methylmercury at the provisional tolerable weekly intake (3.4 µg/kg body weight/week) for adults through fish consumption for 14 weeks, followed by a 15-week washout period after the cessation of exposure. Blood was collected every 1 or 2 weeks, and hair was cut every 4 weeks. Total mercury (T-Hg) concentrations were analyzed in blood and hair. The T-Hg levels of blood and hair changed with time (p < 0.001). The mean concentrations increased from 6.7 ng/g at week 0 to 26.9 ng/g at week 14 in blood, and from 2.3 to 8.8 µg/g in hair. The mean hair-to-blood ratio after the adjustment for the time lag from blood to hair was 344 ± 54 (S.D.) for the entire period. The half-lives of T-Hg were calculated from raw data to be 94 ± 23 days for blood and 102 ± 31 days for hair, but the half-lives recalculated after subtracting the background levels from the raw data were 57 ± 18 and 64 ± 22 days, respectively. In conclusion, the hair-to-blood ratio of methylmercury, based on past studies, appears to be underestimated in light of recent studies. The crude half-life may be preferred rather than the recalculated one because of the practicability and uncertainties of the background level, though the latter half-life may approximate the conventional one.",
"title": "Hair-to-blood ratio and biological half-life of mercury: experimental study of methylmercury exposure through fish consumption in humans."
},
{
"docid": "MED-3270",
"text": "Aging affects all organisms and its basic mechanisms are expected to be conserved across species. Oxidation of proteins has been proposed to be one of the basic mechanisms linking oxygen radicals with the basic aging process. If oxidative damage to proteins is involved in aging, long-lived animals (which age slowly) should show lower levels of markers of this kind of damage than short-lived ones. However, this possibility has not been investigated yet. In this study, steady-state levels of markers of different kinds of protein damage--oxidation (glutamic and aminoadipic semialdehydes), mixed glyco- and lipoxidation (carboxymethyl- and carboxyethyllysine), lipoxidation (malondialdehydelysine) and amino acid composition--were measured in the heart of eight mammalian species ranging in maximum life span (MLSP) from 3.5 to 46 years. Oxidation markers were directly correlated with MLSP across species. Mixed glyco- and lipoxidation markers did not correlate with MLSP. However, the lipoxidation marker malondialdehydelysine was inversely correlated with MLSP (r2=0.85; P<0.001). The amino acid compositional analysis revealed that methionine is the only amino acid strongly correlated MLSP and that such correlation is negative (r2=0.93; P<0.001). This trait may contribute to lower steady-state levels of oxidized methionine residues in cellular proteins. These results reinforce the notion that high longevity in homeothermic vertebrates is achieved in part by constitutively decreasing the sensitivity of both tissue proteins and lipids to oxidative damage. This is obtained by modifying the constituent structural components of proteins and lipids, selecting those less sensitive to oxidative modifications.",
"title": "Protein methionine content and MDA-lysine adducts are inversely related to maximum life span in the heart of mammals."
},
{
"docid": "MED-4835",
"text": "OBJECTIVE: Weight loss and consumption of viscous fibers both lower low-density lipoprotein (LDL) cholesterol levels. We evaluated whether or not a whole-grain, ready-to-eat (RTE) oat cereal containing viscous fiber, as part of a dietary program for weight loss, lowers LDL cholesterol levels and improves other cardiovascular disease risk markers more than a dietary program alone. DESIGN: Randomized, parallel-arm, controlled trial. SUBJECTS/SETTING: Free-living, overweight and obese adults (N=204, body mass index 25 to 45) with baseline LDL cholesterol levels 130 to 200 mg/dL (3.4 to 5.2 mmol/L) were randomized; 144 were included in the main analysis of participants who completed the trial without significant protocol violations. INTERVENTION: Two portions per day of whole-grain RTE oat cereal (3 g/day oat b-glucan) or energy-matched low-fiber foods (control), as part of a reduced energy ( approximately 500 kcal/day deficit) dietary program that encouraged limiting consumption of foods high in energy and fat, portion control, and regular physical activity. MAIN OUTCOME MEASURES: Fasting lipoprotein levels, waist circumference, triceps skinfold thickness, and body weight were measured at baseline and weeks 4, 8, 10, and 12. RESULTS: LDL cholesterol level was reduced significantly more with whole-grain RTE oat cereal vs control (-8.7+/-1.0 vs -4.3+/-1.1%, P=0.005). Total cholesterol (-5.4+/-0.8 vs -2.9+/-0.9%, P=0.038) and non-high-density lipoprotein-cholesterol (-6.3+/-1.0 vs -3.3+/-1.1%, P=0.046) were also lowered significantly more with whole-grain RTE oat cereal, whereas high-density lipoprotein and triglyceride responses did not differ between groups. Weight loss was not different between groups (-2.2+/-0.3 vs -1.7+/-0.3 kg, P=0.325), but waist circumference decreased more (-3.3+/-0.4 vs -1.9+/-0.4 cm, P=0.012) with whole-grain RTE oat cereal. Larger reductions in LDL, total, and non-high-density lipoprotein cholesterol levels and waist circumference were evident as early as week 4 in the whole-grain RTE oat cereal group. CONCLUSIONS: Consumption of a whole-grain RTE oat cereal as part of a dietary program for weight loss had favorable effects on fasting lipid levels and waist circumference. Copyright 2010 American Dietetic Association. Published by Elsevier Inc. All rights reserved.",
"title": "Whole-grain ready-to-eat oat cereal, as part of a dietary program for weight loss, reduces low-density lipoprotein cholesterol in adults with overw..."
},
{
"docid": "MED-5041",
"text": "Substantial data suggest that flavonoid-rich food could help prevent cardiovascular disease and cancer. Cocoa is the richest source of flavonoids, but current processing reduces the content substantially. The Kuna living in the San Blas drink a flavanol-rich cocoa as their main beverage, contributing more than 900 mg/day and thus probably have the most flavonoid-rich diet of any population. We used diagnosis on death certificates to compare cause-specific death rates from year 2000 to 2004 in mainland and the San Blas islands where only Kuna live. Our hypothesis was that if the high flavanoid intake and consequent nitric oxide system activation were important the result would be a reduction in the frequency of ischemic heart disease, stroke, diabetes mellitus, and cancer – all nitric oxide sensitive processes. There were 77,375 deaths in mainland Panama and 558 deaths in the San Blas. In mainland Panama, as anticipated, cardiovascular disease was the leading cause of death (83.4 ± 0.70 age adjusted deaths/100,000) and cancer was second (68.4 ± 1.6). In contrast, the rate of CVD and cancer among island-dwelling Kuna was much lower (9.2 ± 3.1) and (4.4 ± 4.4) respectively. Similarly deaths due to diabetes mellitus were much more common in the mainland (24.1 ± 0.74) than in the San Blas (6.6 ± 1.94). This comparatively lower risk among Kuna in the San Blas from the most common causes of morbidity and mortality in much of the world, possibly reflects a very high flavanol intake and sustained nitric oxide synthesis activation. However, there are many risk factors and an observational study cannot provide definitive evidence.",
"title": "Does Flavanol Intake Influence Mortality from Nitric Oxide-Dependent Processes? Ischemic Heart Disease, Stroke, Diabetes Mellitus, and Cancer in Panama"
}
] |
10031
|
Moving from India to Europe - Bank accounts and Mutual funds
|
[
{
"docid": "467169",
"text": "Once you become NRI or know for sure you would be one, you can't hold ordinary accounts. Convert existing savings account into NRO. Open new NRE account so it's easier to move funds. In simple terms an NRE type of account means you can repatriate the funds outside of India anytime without any paperwork, there are some tax benefits as well. MFU platform can be used for operating demat, else you need a brokerage account. If you have stocks, then existing demat need to be converted to NONPINS account, it's actually open new, move, close old. Any new stock you need to open a PINS Demat account. You can use NRO account of MFU, it creates some complexity of taxes... MFU NRE would be more easier for taxes and flexible for repatriation",
"title": ""
}
] |
[
{
"docid": "16068",
"text": "I have not opened any NRE/NRO account before coming to Finland. This is in violation of Foreign Exchange Management Act. Please get this regularized ASAP. All your savings account need to be converted to NRO. Shall I transfer funds from abroad to both NRE and NRO account or I can transfer only to NRE account in India? You can transfer to NRE or NRO. It is advisable to transfer into NRE as funds from here can be repatriated out of India without any paperwork. Funds from NRO account need paperwork to move out of India. I am a regular tax payer in abroad. The Funds which i'll transfer in future will attract any additional tax in India? As your status is Non Resident and the income is during that period, there is no tax applicable in India on this. Few Mutual Fund SIPs (monthly basis) are linked with my existing saving account in india. Do these SIPs will stop when the savings account will turn into NRO account? Shall I need to submit any documents for KYC compliance? If yes, to whom I should submit these? is there any possibility to submit it Online? Check your Bank / Mutual Fund company. Couple of FDs are also opened online and linked with this existing saving account. Do the maturity amount(s) subject to TDS or any tax implication such as 30.9% as this account will be turned into NRO account till that time and NRO account attracts this higher tax percentage. These are subject to taxes in India. This will be as per standard tax brackets. Which account (NRE/NRO) is better for paying EMIs for Home Loan, SIPs of Mutual Funds, utility bills in India, transfer money to relative's account etc Home Loan would be better from NRE account as if you sell the house, the EMI paid can be credited into NRE account and you can transfer this out of India without much paperwork. Same for SIP's. For other it doesn't really matter as it is an expense. Is there any charge to transfer fund from NRE to NRO account if both account maintain in same Bank same branch. Generally No. Check with your bank. Which Bank account's (NRE/NRO) debit/ATM card should be used in Abroad in case of emergency. Check with your bank. NRE funds are more easy. NRO there will be limits and reporting. Do my other savings accounts, maintained in different Banks, also need to be converted into NRO account? If yes, how can it be done from Abroad? Yes. ASAP. Quite a few leading banks allow you to do this if you are not present. Check you bank for guidance.",
"title": ""
},
{
"docid": "312191",
"text": "How would I go about doing this? Assuming you had purchased the house by funding from your NRE account, you can easily move back the 30K into NRE Account and out of India from NRI Account. The 30K profit would be taxed in India as per capital gains and can only be moved into NRO account. A CA would need to certify that appropriate taxes have been withheld before the bank will release the funds for repatriation out of India. There is also a limit [large 1 million USD] on how much funds can be moved out of India. Consult a CA who would help you with the formalities. If you have not funded the purchase from NRE account, the entire proceeds should be into NRO account and then move funds from there.",
"title": ""
},
{
"docid": "521753",
"text": "I am on employment based visa in USA and want to send dollars from USA to India from my savings (after paying Tax). How much maximum dollars I can send in a day? month? or in a year regularly? There is no such limit. You can transfer as money you like to yourself anywhere. To pay the Bank Loan-student Loan how much maximum dollars I can send in a day, in a month or in a year? to pay that I have to pay directly to that Bank Account or in any account I can send money? You can transfer to your NRE account in India and move it further. You can also send it directly to the Loan Account [Check with the Bank, they may not be able to receive funds from outside for a Loan Account] My mother is having Green Card. She is not working. She has a NRE account in India. Can I send dollars from my USA Bank account to her NRE account in India? what are the rules for that? any Tax or limit for that? Or I have to get any permission before sending it? If you are sending money to your mother, it would come under Gift Tax act in US. There is no issue in India. Suggest you transfer to your own NRE account.",
"title": ""
},
{
"docid": "203889",
"text": "We have a house here in India worth Rs. 2 Crores. We want to sell it and take money with us. Selling the house in India will attract Capital Gains Tax. Essentially the price at which you sell the property less of the property was purchased [or deemed value when inherited by you]. The difference is Capital Gains. You have to pay tax on this gains. This is currently at 10% without Indexation and 20% with Indexation. Please note if you hold these funds for more than an year, you would additionally be liable for Wealth tax at 1% above Rs 50 lacs. Can I gift this whole amount to my US Citizen Daughter or what is the maximum limit of Gift amount What will be the tax liability on me and on my Daughter in case of Gift Whether I have to show it in my Income Tax Return or in my Daughter's Tax Return. What US Income Tax Laws says. What will be the procedure to send money as Gift to my Daughter. Assuming you are still Indian citizen when to gift the funds; From Indian tax point of you there is no tax to you. As you daughter is US citizen, there is no gift tax to her. There is no limit in India or US. So you can effectively gift the entire amount without any taxes. If you transfer this after you become a US Resident [for tax purposes], then there is a limit of USD 14,000/- per year per recipient. Effective you can gift your daughter and son-in-law 14,000/- ea and your husband can do the same. Net 14,000 * 4 USD per year. Beyond this you either pay tax or declare this and deduct it from life time estate quota. Again there is no tax for your daughter. What are the routes to take money from India to US Will the money will go directly from my Bank Act.to my Daughter's Bank Account. Will there will be wire transfer from bank to bank Can I send money through other money sender Certified Companies also. The best way is via Bank to Bank transfer. A CA Certificate is required to certify that taxes have been paid on this funds being transferred. Under the liberalized remittance scheme in India, there is a limit of USD 1 Million per year for moving funds outside of India. So you can move around Rs 6-7 Crore a year.",
"title": ""
},
{
"docid": "495315",
"text": "Is it possible to move money from NRE to NRO account Yes you can move money from NRE to NRO without any issue. You can't do the other way round. i.e. Move money from NRO to NRE. I would like to move USD earning to NRE Yes you can further move money in NRE to NRO account Yes you can I am planning to give NRO account to HDFC Home loan for EMI processing Yes you can. Depending on your long term plan it may not be a good idea. For example if you were to sell the house you cannot move the funds into NRE and outside of India without some amount of paperwork. However if you pay the EMI via NRE account, on the sale of house, you can transfer the funds into NRE account to the extent of the loan paid and the Original downpayment [if made from NRE account]. also I can deposit money from other savings account to NRO; As an NRI, you can't hold ordinary savings account in India. This is violation of norms. Please have any/all savings account in India converted to NRO at the earliest.",
"title": ""
},
{
"docid": "187734",
"text": "\"The Option 2 in your answer is how most of the money is moved cross border. It is called International Transfer, most of it carried out using the SWIFT network. This is expensive, at a minimum it costs in the range of USD 30 to USD 50. This becomes a expensive mechanism to transfer small sums of money that individuals are typically looking at. Over a period of years, the low value payments by individuals between certain pair of countries is quite high, example US-India, US-China, Middle-East-India, US-Mexico etc ... With the intention to reduce cost, Banks have built a different work-flow, this is the Option 1. This essentially works on getting money from multiple individuals in EUR. The aggregated sum is converted into INR, then transferred to partner Bank in India via Single SWIFT. Alongside the partner bank is also sent a file of instructions having the credit account. The Partner Bank in India will use the local clearing network [these days NEFT] to credit the funds to the Indian account. Option 3: Other methods include you writing a check in EUR and sending it over to a friend/relative in India to deposit this into Indian Account. Typically very nominal costs. Typically one month of timelines. Option 4: Another method would be to visit an Indian Bank and ask them to issue a \"\"Rupee Draft/Bankers Check\"\" payable in India. The charges for this would be higher than Option 3, less than Option 1. Mail this to friend/relative in India to deposit this into Indian Account. Typically couple of days timelines for transfer to happen.\"",
"title": ""
},
{
"docid": "448981",
"text": "am I allowed to transfer into NRE account from paypal? Credits into NRE accounts are restricted. It has to be established that the funds being credited are income outside of India. In case of paypal, paypal uses local clearing to credit funds into Bank Accounts. So essentially one cannot credit NRE account by domestic clearing network like NEFT. It is best that you withdraw the funds into Bank Account outside India and use SWIFT or remittance service to credit your NRE account. I do not want to transfer to an NRO account since the money credited into it will become taxable. This is not the right assumption. Credits into NRO are not taxable by default; if you establish that the funds are from outside India, there is no tax on the income money transferred from abroad into the NRO account. However, the interest that will be paid by the bank on the balance of the NRO account is taxable income in India and is subject to TDS. In contrast, interest paid on the balance in an NRE account is not taxable in India and is not subject to TDS as long as you maintain NRI status. However it does make sense to keep accounts segregated, i.e. income generated in India, credit the NRO account and income generated outside India credit to NRE.",
"title": ""
},
{
"docid": "146557",
"text": "What are the steps to bring the money to the US? It is worth 1.25 Crore and I have already paid the 20% tax in India. Under the Liberalized Remittance Scheme an Individual can repatriate funds upto USD 250,000 without any paperwork. However most banks would be cautious and request for Form 15CA and Form 15CB if you are moving funds from NRO Account. Form 15 CA you would need to declare why you are moving the said funds. The Form 15 CB is to be filled by Chartered Account certifying that relevant taxes have been already paid to Income Tax. Most Banks would offer these services. Compare the Fx Rate and Fees before you make a decision as to which Bank to proceed with.",
"title": ""
},
{
"docid": "263648",
"text": "On my recent visit to the bank, I was told that money coming into the NRE account can only be foreign currency and for NRO accounts, the money can come in local currency but has to be a valid source of income (e.g. rent or investments in India). Yes this is correct as per FMEA regulation in India. Now if we use 3rd party remittances like Remitly or Transferwise etc, they usually covert the foreign currency into local currency like INR and then deposit it. The remittance services are better suited for transferring funds to Normal Savings accounts of your loved ones. Most remittance services would transfer funds using a domestic clearing network [NEFT] and hence the trace that funds originated outside of India is lost. There could be some generic remittance that may have direct tie-up with some banks to do direct transfers. How can we achieve this in either NRE/NRO accounts? If not, what are the other options ? You can do a Wire Transfer [SWIFT] from US to Indian NRE account. You can also use the remittance services [if available] from Banks where you hold NRE Account. For example RemittoIndia from HDFC for an NRE account in HDFC, or Money2India from ICICI for an NRE account in ICICI or QuickRemit from SBI etc. These would preserve the history that funds originated from outside India. Similarly you can also deposit a Foreign Currency Check into Indian Bank Account. The funds would take around month or so to get credited. All other funds can be deposited in NRO account.",
"title": ""
},
{
"docid": "487890",
"text": "\"An alternative to a savings account is a money market account. Not a bank \"\"Money Market\"\" account which pays effectively the same silly rate as a savings account, but an actual Money Market investment account. You can even write checks against some Money Market investment accounts. I have several accounts worth about 13,000 each. Originally, my \"\"emergency fund\"\" was in a CD ladder. I started experimenting with two different Money market investment accounts recently. Here's my latest results: August returns on various accounts worth about $13k: - Discover Bank CD: $13.22 - Discover Bank CD: $13.27 - Discover Bank CD: $13.20 - Discover Savings: $13.18 - Credit Union \"\"Money Market\"\" Savings account: $1.80 - Fidelity Money Market Account (SPAXX): $7.35 - Vanguard Money market Account (VMFXX): $10.86 The actual account values are approximate. The Fidelity Money Market Account holds the least value, and the Credit Union account by far the most. The result of the experiment is that as the CDs mature, I'll be moving out of Discover Bank into the Vanguard Money Market account. You can put your money into more traditional equities mutual fund. The danger with them is the stock market may drop big the day before you want to make your withdrawl... and then you don't have the down payment for your house anymore. But a well chosen mutual fund will yield better. There are 3 ways a mutual fund increase in value: Here's how three of my mutual funds did in the past month... adjusted as if the accounts had started off to be worth about $13,000: Those must vary wildly month-to-month. By the way, if you look up the ticker symbols, VASGX is a Vanguard \"\"Fund of Funds\"\" -- it invests not 100% in the stock market, but 80% in the stock market and 20% in bonds. VSMGX is a 60/40 split. Interesting that VASGX grew less than VSMGX...but that assumes my spreadsheet is correct. Most of my mutual funds pay dividends and capital gains once or twice a year. I don't think any pay in August.\"",
"title": ""
},
{
"docid": "277475",
"text": "One of my friend is sending 100000 pounds to India, Although you haven't asked, this is a large amount of funds and depending on why it is, there could be taxes to you or lot of paperwork. He is asking for RIB and IBAN and I am not aware of it. India does not have IBAN. IBAN is mostly in Europe, Australia and New Zealand. You would need to give Bank Account Number and SWIFT BIC. The details can be found here. Best talk to your Branch to understand.",
"title": ""
},
{
"docid": "516756",
"text": "As you are not a tax resident in India, the income you have earned can be moved to India tax free. However if you are investing the funds into say shares / fixed deposits etc, the income you earn on these funds is taxable in India. The funds can be transferred directly into savings account. However its advisible to open an NRE/NRO account as its easier to track funds for tax purposes. i.e. these accounts by nature certify that the funds received into them are from foreign sources and can easily be explained to the tax authorities. However establishing the origin of funds in ordinary savings accounts needs more paper work. Whenever there is a scrutiny by tax authorities on this savings account, it would need more efforts to establish that the credits are from foreign earnings.",
"title": ""
},
{
"docid": "193842",
"text": "You would need to pay tax on the 10% gain. Was this money loaned from your NRE account? Is there paperwork to show that there was this loan given? If yes then it would be easy to get this back into NRE account. Once in NRE account you can move this back to US without any issue. If not, then you can get this into NRO account. From NRO account you would need to consult a CA to do some paperwork [essentially certifying that you have paid all taxes due] so that funds can be remitted outside. Edit: Looks like you have completed all formalities. A credit to NRE Account can only happen from funds outside of India. However a credit from India into NRE account can happen under some circumstances, like Loan give and received back. You would need a CA in India to help you complete the formalities. The tax is due in India as this was due to gain in India. As you are US resident for tax purposes, and US taxes global income, this is taxable in US as well. You can claim relief in US to the extent of taxes paid in India. India and US have DTAA.",
"title": ""
},
{
"docid": "271415",
"text": "As an NRI, you can't hold a regular savings account. It should have been converted to NRO. Option 1: Open NRE account : Since I am relocating permanently this might not be good option for me as converting This is the best Option as funds into NRE are not taxable in India. The provides a clean paper trail so that if there are any tax queries, you can answer them easily. You can open a Rupee NRE account, move the funds. On return move the funds into Normal Savings account and close the NRE account. This is not much of hassle. Option 2: Create NRO account: There would be taxes on the interest earned of the funds. But I am not sure of this, since I will have been moved to India permanently would I need to still pay taxes on the interest earned while I am in India? Any interest in NRO or normal savings account is taxable in India. There is no exemption. Option 3: I can transfer my funds directly to my account in India but I believe I would have to pay tax on the the funds that I transfer and that would be double taxation. Which I think would be the worst option for me. Please correct me if I am wrong. This is incorrect. Any earnings outside of India when your status is NRI, is not taxable in India. Opening an NRE account provides proper paper trail of funds. As an NRI one cannot hold normal savings account. This should have been converted into an NRO account. Although there is no penalty prescribed, its violation of FEMA regulation. I also hope you were declaring any income in India, i.e. interest etc on savings and filing returns accordingly. Option 4: I can transfer the funds to my direct relatives account. I still believe there would be tax to be paid on the interest earned of the amount. You can transfer it to your parents / siblings / etc. This would come under gift tax purview and would not be taxable. They can then gift this back to you. However such transactions would appear to be evading regulations and may come under scrutiny. Interest on Savings account is taxable. So best is go with Option 1. No hassle. Else go with Option 3, but ensure that you have all the paperwork kept handy for next 7 years.",
"title": ""
},
{
"docid": "539263",
"text": "There are times when investing in an ETF is more convenient than a mutual fund. When you invest in a mutual fund, you often have an account directly with the mutual fund company, or you have an account with a mutual fund broker. Mutual funds often have either a front end or back end load, which essentially gives you a penalty for jumping in and out of funds. ETFs are traded exactly like stocks, so there is inherently no load when buying or selling. If you have a brokerage account and you want to move funds from a stock to a mutual fund, an ETF might be more convenient. With some accounts, an ETF allows you to invest in a fund that you would not be able to invest in otherwise. For example, you might have a 401k account through your employer. You might want to invest in a Vanguard mutual fund, but Vanguard funds are not available with your 401k. If you have access to a brokerage account inside your 401k, you can invest in the Vanguard fund through the associated ETF. Another reason that you might choose an ETF over a mutual fund is if you want to try to short the fund.",
"title": ""
},
{
"docid": "13215",
"text": "\"No, you do not need an OCI card to continue to have an NRE or NRO account. You are now classified as a PIO -- Person of Indian Origin -- (and you don't need to have a PIO card issued by the Government of India to prove it) and are entitled to use NRE and NRO accounts just as you were when you were a NRI (NonResident Indian). But, you should inform the banks where you have NRE and NRO accounts that you have changed citizenship, and they may need to go through their KYC (Know Your Customer) process with you all over again. If you don't get an OCI Card, you will need to have an Indian visa stamped into your new US passport to visit India, and please do remember to send your Indian passport to the nearest Indian Consulate for cancellation. Keep the surrender certificate and cancelled passport in your safe deposit box forever; your grandchildren will need it to get visas to visit India. (My granddaughter just did). If you do get an OCI Card, you will need to have an OCI stamp put into your new US passport, and when you renew your US passport, you will need to get the new one stamped too (and pay the fee for that, of course). You cannot enter India with just an OCI Card and a US passport without the OCI stamp in it; that stamp is vital. If you move from one residential address in the US to another, you will need to get a new OCI Card issued because, unlike the US \"\"green card\"\", the OCI card has your residential address on it. Once again, a fee is involved. All these processes take many weeks because the whole paperwork has to go to the Ministry of External Affairs in New Delhi, and meanwhile, your passport is not available to you for a trip to Europe or Japan or Taiwan or China if you need to go there on business (or for pleasure).\"",
"title": ""
},
{
"docid": "450925",
"text": "How to send the full loan amount from Saudi Arabia (money exchange), because I have a money transfer limit? There is no limit for sending money into India. Just use the right banking channel and transfer the funds. If I sent to India, what about tax and all that in India? In a financial year if you are outside of India for more than 182 days, you are Non-Resident for tax purposes. Any money you earn outside of India is tax free in India. i.e. there is no tax for this funds in India. If it is possible to send the money, to whom do I have to send it (my account, or my parents account) Whatever is convenient, preferably to your own NRE/NRO account. Any documents I have to show for tax issues (in case tax) You have to establish that you are NRI and hence this funds are not taxable. Hence its best you transfer into NRE/NRO account. If you transfer to your parents account, you would need a gift deed to make this non-taxable to your parents. I have savings account my self in Axis Bank, for the past 3 years I am paying taxes, if I send to my Axis Bank account how can I withdraw the full amount (10 lakhs (1,000,000)) on single day Withdrawal is possible by cash or cheque You can write a check, do a NEFT/RTGS transfer to your loan account, you can withdraw cash by giving some notice time to the Branch Manager of your Branch.",
"title": ""
},
{
"docid": "153528",
"text": "For the financial year 1 April 2014 to 31 March 2015 as you have / will be spending more than 182 days outside of India, you are Non-Resident from tax point of view. For the period 1 April 2014 to Aug 2014, any salary / income you have earned in India is taxable and tax need to be paid. For the period Aug 2014 to 31 March 2015 the income you have earned in Saudi is not taxable in India. You can transfer money to India or keep in Saudi, it has no effect on the taxes. Any interest income you earn, or rental income you earn, or any other source of income in India is taxable. You would need to file returns accordingly. An NRE Accounts allows you to transfer funds out of India without any questions. So if you intend at some point in time in future to move funds out of India [say settling down in Saudi or UK or US etc] it is advisable to have NRE account. If you are sure you don't want to transfer funds out of India, you should open an NRO account.",
"title": ""
},
{
"docid": "417769",
"text": "How do I directly get my Freelancing amount in my Axis bank account? Do I need to inform my Bank before receiving any such payment? Yes you can get it directly into your Axis Bank Account. You would need to inform your client your Bank Account Number, Bank Name and Address and Swift BIC or IFSC Code [Axis Bank website or Branch can tell you]. You can receive credits in Euro's. Upon receipt Axis Bank will automatically convert this into Rupees using standard rate. Your Bank [Axis] may also charge some Bank fees for the wire transfer. How do I pay tax for this extra income in India? You would need to treat this as income and add it to total income including salary and calculate tax accordingly. You can pay taxes online using Income Tax India website. You can also approach a CA who would do the tax computation, paying taxes and filing returns for as little as Rs 1000 - 2000/- Edit: IBAN is International Bank Account Number. Explain to you client that India does not subscribe to IBAN. Its right now only used by Europe and Australia. Give you normal Bank Account Number. Please call up your Bank / walk into your Branch to get the SWIFT BIC. It will be something like this http://www.theswiftcodes.com/india/page/3/",
"title": ""
},
{
"docid": "449124",
"text": "In addition to all the good information that JoeTaxpayer has provided, be aware of this. When you sell mutual fund shares, you can, if you choose to do so, tell the mutual fund company which shares you want to sell (e.g. all shares purchased on xx/yy/2010 plus 10 shares out of 23.147 shares purchased on ss/tt/2011 plus...) and pay taxes on the gains/losses on those specific shares. If you do not specify which shares you want sold, the mutual fund company will tell you the gains/losses based on the average cost basis and you can use this information if you like. Note that some of your gains/losses will be short-term gains or losses if you use the average cost basis. Or, you can use the FIFO method (usually resulting in the largest gain) in which the shares are sold in the order in which they were purchased. This usually results in no short-term gains/losses. Just so that you know, most mutual fund companies will link your checking account in your bank to your account with them (a one-time paperwork deal is necessary in which your bank manager's signature is required on the authorization to be sent to the fund company). After that, the connection is nearly as seamless as with your current system. Tell the fund company you want to invest money in a certain mutual fund and to take the money from your linked checking account, and they will take care of it. Sell some shares and they will deposit the money into your linked bank account, and so on. The mutual fund company will not accept instructions from you (or someone purporting to be you) to sell shares and to send the money to Joe Blow (or to Joe Taxpayer for that matter): the proceeds of redemptions go to your checking account or are used to buy shares in other mutual funds offered by the company (called an exchange and not a redemption). Oh, and most fund companies offer automatic investments (as well as automatic redemptions) at fixed time intervals, just as with your bank.",
"title": ""
},
{
"docid": "307404",
"text": "I am a non-resident alien transferring a limited amount ( in dollars post tax) to India every couple of months. Assuming you are transferring this into an NRE account in India or atleast NRO account in India. As a NRI, by regulations one should not hold normal Savings account. This has to be converted into NRO. I put that money as a fixed deposit in a bank (which gives 6-7 percent annual return) Assuming you have FCNR deposits. Also assuming that you are declaring the taxes in your US Tax returns and paying tax accordingly. There is no tax in India on FCNR. If this was in ordinary FD or in NRO account, you are declaring and paying taxes in India as well as in US. What is the max limit on transferring money back from India to USA? If you have transferred this into NRE account, there is no limit. Other account there is a limit. Read more at Liberalized Remittance Scheme and here. What are the legitimate ways to transfer the money? From India point of view, this has to be Bank to Bank transfers. You can't carry cash [Indian Rupees] outside of India beyond Rs 25000 [or 15000?]. You can't hold excess of USD 250 without valid purpose. Western Union is not authorized to transfer funds out of India. Will there be any tax levied? No assuming you are already paying taxes on the Interest in US and depending on the type of account in India.",
"title": ""
},
{
"docid": "40682",
"text": "I was wondering if I could make part of the payment here in USD legally? Although not directly illegal ... From an India tax and FMEA point of view this would be a bit complicated. A NRI Seller cannot repatriate the proceeds from sale of house unless he had purchased this from NRE account and repatriation is only possible for original purchase amount. For the gains Seller has to apply for repatriation of funds. A NRI Seller has to pay taxes on gains and this transaction should not look like facilitating a tax fraud in case NRI Seller does not pay his taxes. As a Buyer if you make the purchase from your NRE account [i.e. Move US funds into India into NRE Account], it will ease you ability to repatriate funds in future. Depending on the property value and PAN card availability of seller, you have to deduct 1% to 30.12% tax from the value and deposit this with Income Tax India. PS: It is recommended that you consult a Professional CA to help you with modalities.",
"title": ""
},
{
"docid": "446647",
"text": "I want to send some money to Indian in my saving account but I haven't any NRO/NRE account. It is advisable to Open an NRE account. As an NRI you cannot hold a savings account. Please have this converted into NRO account ASAP. Process or Transaction charges or Tax (levied by Indian bank) on money what I'll send to my saving account in India. I know the process or transaction charges (applied by UK banks) from UK to India. There will be a nominal charge levied by banks in India. If you use dedicated Remittance services [Most Leading Indian Banks offer this], these are mostly free. Is there any limit to get rid off tax? Nope there isn't any limit. This depends on service provider. What types of paper work I'll need to do for showing that income is sent from UK after paying tax. If you transfer to NRE account. There is no paperwork required. It is implicit. If not you have to establish that the funds are received from outside India, keep copies of the transfer request initiated, debits to the Bank Account in UK, your salary slips, Passport stamps etc.",
"title": ""
},
{
"docid": "575241",
"text": "Part 1 Quite a few [or rather most] countries allow USD account. So there is no conversion. Just to illustrare; In India its allowed to have a USD account. The funds can be transfered as USD and withdrawn as USD, the interest is in USD. There no conversion at any point in time. Typically the rates for CD on USD account was Central Bank regulated rate of 5%, recently this was deregulated, and some banks offer around 7% interest. Why is the rate high on USD in India? - There is a trade deficit which means India gets less USD and has to pay More USD to buy stuff [Oil and other essential items]. - The balance is typically borrowed say from IMF or other countries etc. - Allowing Banks to offer high interest rate is one way to attract more USD into the country in short term. [because somepoint in time they may take back the USD out of India] So why isn't everyone jumping and making USD investiments in India? - The Non-Residents who eventually plan to come back have invested in USD in India. - There is a risk of regulation changes, ie if the Central Bank / Country comes up pressure for Forex Reserves, they may make it difficut to take back the USD. IE they may impose charges / taxes or force conversion on such accounts. - The KYC norms make it difficult for Indian Bank to attract US citizens [except Non Resident Indians] - Certain countries would have explicit regulations to prevent Other Nationals from investing in such products as they may lead to volatility [ie all of them suddenly pull out the funds] - There would be no insurance to foreign nationals. Part 2 The FDIC insurance is not the reason for lower rates. Most countires have similar insurance for Bank deposits for account holdes. The reason for lower interst rate is all the Goverments [China etc] park the excess funds in US Treasuries because; 1. It is safe 2. It is required for any international purchase 3. It is very liquid. Now if the US Fed started giving higher interest rates to tresaury bonds say 5%, it essentially paying more to other countries ... so its keeping the interest rates low even at 1% there are enough people [institutions / governemnts] who would keep the money with US Treasury. So the US Treasury has to make some revenue from the funds kept at it ... it lends at lower interest rates to Bank ... who in turn lend it to borrowers [both corporate and retail]. Now if they can borrow cheaply from Fed, why would they pay more to Individual Retail on CD?, they will pay less; because the lending rates are low as well. Part 3 Check out the regulations",
"title": ""
},
{
"docid": "585494",
"text": "\"Pay off the credit cards. From now on, pay off the credit cards monthly. Under no circumstances should you borrow money. You have net worth but no external income. Borrowing is useless to you. $200,000 in two bank accounts, because if one bank collapses, you want to have a spare while you wait for the government to pay off the guarantee. Keep $50,000 in checking and another $50k in savings. The remainder put into CDs. Don't expect interest income beyond inflation. Real interest rates (after inflation) are often slightly negative. People ask why you might keep money in the bank rather than stocks/bonds. The problem is that stocks/bonds don't always maintain their value, much less go up. The bank money won't gain, but it won't suddenly lose half its value either. It can easily take five years after a stock market crash for the market to recover. You don't want to be withdrawing from losses. Some people have suggested more bonds and fewer stocks. But putting some of the money in the bank is better than bonds. Bonds sometimes lose money, like stocks. Instead, park some of the money in the bank and pick a more aggressive stock/bond mixture. That way you're never desperate for money, and you can survive market dips. And the stock/bond part of the investment will return more at 70/30 than 60/40. $700,000 in stock mutual funds. $300,000 in bond mutual funds. Look for broad indexes rather than high returns. You need this to grow by the inflation rate just to keep even. That's $20,000 to $30,000 a year. Keep the balance between 70/30 and 75/25. You can move half the excess beyond inflation to your bank accounts. That's the money you have to spend each year. Don't withdraw money if you aren't keeping up with inflation. Don't try to time the market. Much better informed people with better resources will be trying to do that and failing. Play the odds instead. Keep to a consistent strategy and let the market come back to you. If you chase it, you are likely to lose money. If you don't spend money this year, you can save it for next year. Anything beyond $200,000 in the bank accounts is available for spending. In an emergency you may have to draw down the $200,000. Be careful. It's not as big a cushion as it seems, because you don't have an external income to replace it. I live in southern California but would like to move overseas after establishing stable investments. I am not the type of person that would invest in McDonald's, but would consider other less evil franchises (maybe?). These are contradictory goals, as stated. A franchise (meaning a local business of a national brand) is not a \"\"stable investment\"\". A franchise is something that you actively manage. At minimum, you have to hire someone to run the franchise. And as a general rule, they aren't as turnkey as they promise. How do you pick a good manager? How will you tell if they know how the business works? Particularly if you don't know. How will you tell that they are honest and won't just embezzle your money? Or more honestly, give you too much of the business revenues such that the business is not sustainable? Or spend so much on the business that you can't recover it as revenue? Some have suggested that you meant brand or stock rather than franchise. If so, you can ignore the last few paragraphs. I would be careful about making moral judgments about companies. McDonald's pays its workers too little. Google invades privacy. Exxon is bad for the environment. Chase collects fees from people desperate for money. Tesla relies on government subsidies. Every successful company has some way in which it can be considered \"\"evil\"\". And unsuccessful companies are evil in that they go out of business, leaving workers, customers, and investors (i.e. you!) in the lurch. Regardless, you should invest in broad index funds rather than individual stocks. If college is out of the question, then so should be stock investing. It's at least as much work and needs to be maintained. In terms of living overseas, dip your toe in first. Rent a small place for a few months. Find out how much it costs to live there. Remember to leave money for bigger expenses. You should be able to live on $20,000 or $25,000 a year now. Then you can plan on spending $35,000 a year to do it for real (including odd expenses that don't happen every month). Make sure that you have health insurance arranged. Eventually you may buy a place. If you can find one that you can afford for something like $100,000. Note that $100,000 would be low in California but sufficient even in many places in the US. Think rural, like the South or Midwest. And of course that would be more money in many countries in South America, Africa, or southern Asia. Even southern and eastern Europe might be possible. You might even pay a bit more and rent part of the property. In the US, this would be a duplex or a bed and breakfast. They may use different terms elsewhere. Given your health, do you need a maid/cook? That would lean towards something like a bed and breakfast, where the same person can clean for both you and the guests. Same with cooking, although that might be a second person (or more). Hire a bookkeeper/accountant first, as you'll want help evaluating potential purchases. Keep the business small enough that you can actively monitor it. Part of the problem here is that a million dollars sounds like a lot of money but isn't. You aren't rich. This is about bare minimum for surviving with a middle class lifestyle in the United States and other first world countries. You can't live like a tourist. It's true that many places overseas are cheaper. But many aren't (including much of Europe, Japan, Australia, New Zealand, etc.). And the ones that aren't may surprise you. And you also may find that some of the things that you personally want or need to buy are expensive elsewhere. Dabble first and commit slowly; be sure first. Include rarer things like travel in your expenses. Long term, there will be currency rate worries overseas. If you move permanently, you should certainly move your bank accounts there relatively soon (perhaps keep part of one in the US for emergencies that may bring you back). And move your investments as well. Your return may actually improve, although some of that is likely to be eaten up by inflation. A 10% return in a country with 12% inflation is a negative real return. Try to balance your investments by where your money gets spent. If you are eating imported food, put some of the investment in the place from which you are importing. That way, if exchange rates push your food costs up, they will likely increase your investments at the same time. If you are buying stuff online from US vendors and having it shipped to you, keep some of your investments in the US for the same reason. Make currency fluctuations work with you rather than against you. I don't know what your circumstances are in terms of health. If you can work, you probably should. Given twenty years, your million could grow to enough to live off securely. As is, you would be in trouble with another stock market crash. You'd have to live off the bank account money while you waited for your stocks and bonds to recover.\"",
"title": ""
},
{
"docid": "78813",
"text": "The simplest way is you transfer the funds into your NRE account in India. From the NRE account transfer the funds to your brother-in-law and show the purpose as Loan. From 2012 onwards RBI has simplified things under FMEA and your brother-in-law can deposit/repay the loan back into the NRE account. Once the funds are in NRE account you can repatriate then whenever you like. This entire process requires less paperwork. The option you have suggested is also fine, however your brother-in-law needs to engage the services of a CA and he will authenticate the purpose of remittance to the Bank. Based on this certificate the Bank will transfer the funds outside of India.",
"title": ""
},
{
"docid": "286825",
"text": "There is no difference in taxation in India if you transfer every month or bulk. If you use specialized remittance services from leading Indian Banks, there would be little difference in fees. Assuming you are keeping the funds in NRE account in India and hold it in GBP, you get a slight better rate of interest that what you would get in UK. The interest would not be taxable in India, however it would be in UK. If you convert the funds at hold it in NRE, Rupee account, you would get still better rate of interest. However you are taking the Fx risk when you try and convert this back to GBP incase you decide to stay on. There are no right or wrong answers Edit: There is no limit on the amount of funds earned as NRE that can be got into India tax free. There is a time limit of 7 Years to get the funds back to India tax free. From a tax point of view if you transfer into NRE account its easy. If you transfer into Normal Savings account you would need some paperwork.",
"title": ""
},
{
"docid": "153660",
"text": "\"For a non-ETF mutual fund, you can only buy shares of the mutual fund from the mutual fund itself (at a price that the mutual fund will reveal only at the end of the day) and can only shares back to the mutual fund (again at a price that the mutual fund will reveal only at the end of the day). There is no open market in the sense that you cannot put in a bid to buy, say, 100 shares of VFINX at $217 per share through a brokerage, and if there is a seller willing to sell 100 shares of VFINX to you at $217, then the sale is consummated and you are now the proud owner of 100 shares of VFINX. The only buyer or seller of VFINX is the mutual find itself, and you tell it that you \"\"want to buy 100 shares of VFINX and please take the money out of my checking account\"\". If this order is entered before the markets close at 4 pm, the mutual fund determines its share price as of the end of the day, opens a new account for you and puts 100 shares of VFINX in it (or adds 100 shares of VFINX to your already existing pile of shares) and takes the purchase price out of your checking account via an ACH transfer. Similarly for redeeming/selling shares of VFINX that you own (and these are held in an account at the mutual fund itself, not by your brokerage): you tell the mutual fund to that you \"\"wish to redeem 100 shares and please send the proceeds to my bank account\"\" and the mutual fund does this at the end of the day, and the money appears in your bank account via ACH transfer two or three days later. Generally, these transactions do not need to be for round lots of multiples of 100 shares for efficiency; most mutual fund will gladly sell you fractional shares down to a thousandth of a share. In contrast, shares of an exchange-traded fund (ETF) are just like stock shares in that they can be bought and sold on the open market and your broker will charge you fees for buying and selling them. Selling fractional shares on the open market is generally not possible, and trading in round lots is less expensive. Also, trades occur at all times of the stock exchange day, not just at the end of the day as with non-ETF funds, and the price can fluctuate during the day too. Many non-ETF mutual funds have an ETF equivalent: VOO is the symbol for Vanguard's S&P 500 Index ETF while VFINX is the non-ETF version of the same index fund. Read more about the differences between ETFs and mutual funds, for example, here.\"",
"title": ""
},
{
"docid": "88575",
"text": "\"A mutual fund's return or yield has nothing to do with what you receive from the mutual fund. The annual percentage return is simply the percentage increase (or decrease!) of the value of one share of the mutual fund from January 1 till December 31. The cash value of any distributions (dividend income, short-term capital gains, long-term capital gains) might be reported separately or might be included in the annual return. What you receive from the mutual fund is the distributions which you have the option of taking in cash (and spending on whatever you like, or investing elsewhere) or of re-investing into the fund without ever actually touching the money. Regardless of whether you take a distribution as cash or re-invest it in the mutual fund, that amount is taxable income in most jurisdictions. In the US, long-term capital gains are taxed at different (lower) rates than ordinary income, and I believe that long-term capital gains from mutual funds are not taxed at all in India. You are not taxed on the increase in the value of your investment caused by an increase in the share price over the year nor do you get deduct the \"\"loss\"\" if the share price declined over the year. It is only when you sell the mutual fund shares (back to the mutual fund company) that you have to pay taxes on the capital gains (if you sold for a higher price) or deduct the capital loss (if you sold for a lower price) than the purchase price of the shares. Be aware that different shares in the sale might have different purchase prices because they were bought at different times, and thus have different gains and losses. So, how do you calculate your personal return from the mutual fund investment? If you have a money management program or a spreadsheet program, it can calculate your return for you. If you have online access to your mutual fund account on its website, it will most likely have a tool called something like \"\"Personal rate of return\"\" and this will provide you with the same calculations without your having to type in all the data by hand. Finally, If you want to do it personally by hand, I am sure that someone will soon post an answer writing out the gory details.\"",
"title": ""
},
{
"docid": "183898",
"text": "It is true that this is possible, however, it's very remote in the case of the large and reputable fund companies such as Vanguard. FDIC insurance protects against precisely this for bank accounts, but mutual funds and ETFs do not have an equivalent to FDIC insurance. One thing that does help you in the case of a mutual fund or ETF is that you indirectly (through the fund) own actual assets. In a cash account at a bank, you have a promise from the bank to pay, and then the bank can go off and use your money to make loans. You don't in any sense own the bank's loans. With a fund, the fund company cannot (legally) take your money out of the fund, except to pay the expense ratio. They have to use your money to buy stocks, bonds, or whatever the fund invests in. Those assets are then owned by the fund. Legally, a mutual fund is a special kind of company defined in the Investment Company Act of 1940, and is a separate company from the investment advisor (such as Vanguard): http://www.sec.gov/answers/mfinvco.htm Funds have their own boards, and in principle a fund board can even fire the company advising the fund, though this is not likely since boards aren't usually independent. (a quick google found this article for more, maybe someone can find a better one: http://www.marketwatch.com/story/mutual-fund-independent-board-rule-all-but-dead) If Vanguard goes under, the funds could continue to exist and get a new adviser, or could be liquidated with investors receiving whatever the assets are worth. Of course, all this legal stuff doesn't help you with outright fraud. If a fund's adviser says it bought the S&P 500, but really some guy bought himself a yacht, Madoff-style, then you have a problem. But a huge well-known ETF has auditors, tons of different employees, lots of brokerage and exchange traffic, etc. so to me at least it's tough to imagine a risk here. With a small fund company with just a few people - and there are lots of these! - then there's more risk, and you'd want to carefully look at what independent agent holds their assets, who their auditors are, and so forth. With regular mutual funds (not ETFs) there are more issues with diversifying across fund companies: With ETFs, there probably isn't much downside to diversifying since you could buy them all from one brokerage account. Maybe it even happens naturally if you pick the best ETFs you can find. Personally, I would just pick the best ETFs and not worry about advisor diversity. Update: maybe also deserving a mention are exchange-traded notes (ETNs). An ETN's legal structure is more like the bank account, minus the FDIC insurance of course. It's an IOU from the company that runs the ETN, where they promise to pay back the value of some index. There's no investment company as with a fund, and therefore you don't own a share of any actual assets. If the ETN's sponsor went bankrupt, you would indeed have a problem, much more so than if an ETF's sponsor went bankrupt.",
"title": ""
}
] |
PLAIN-1188
|
fisitin
|
[
{
"docid": "MED-3548",
"text": "Cancer metastasis refers to the spread of cancer cells from the primary neoplasm to distant sites, where secondary tumors are formed, and is the major cause of death from cancer. Natural phytochemicals containing phenolic compounds have been widely demonstrated to have the capability to prevent cancer metastasis. Among phenolic compounds, flavonoids are a very large subclass, and they are abundant in food and nutraceuticals. The number of reports demonstrating that flavonoids are an effective natural inhibitor of cancer invasion and metastasis is increasing in the scientific literature. Catechin derivatives, (−)-epigallocatechin-3-gallate, (−)-epigallocatechin, (−)-epicatechin-3-gallate,and (−)-epicatechin, are the most studied compounds in this topic so far; genistein/genistin, silibinin, quercetin, and anthocyanin have also been widely investigated for their inhibitory activities on invasion/metastasis. Other flavonoids in dietary vegetable foods that are responsible for anti-invasive and anti-metastatic activities of tumors include luteolin,apigenin, myricetin, tangeretin, kaempferol, glycitein, licoricidin,daidzein, and naringenin. To effectively overcome the metastatic cascade, including cell-cell attachment, tissue barrier degradation, migration, invasion, cell-matrix adhesion,and angiogenesis, it is essential that a bioactive compound prevent tumor cells from metastasizing. This review summarizes the effects of flavonoids on the metastatic cascade and the related proteins, the in vitro anti-invasive activity of flavonoids against cancer cells, and the effects of flavonoids on antiangiogenic and in vivo anti-metastatic models. The available scientific evidence indicates that flavonoids are a ubiquitous dietary phenolics subclass and exert extensive in vitro anti-invasive and in vivo anti-metastatic activities.",
"title": "Flavonoids, a ubiquitous dietary phenolic subclass, exert extensive in vitro anti-invasive and in vivo anti-metastatic activities."
},
{
"docid": "MED-3553",
"text": "Several epidemiological studies have indicated that abundant consumption of foods from plant origin is associated with a reduced risk of developing several types of cancers. This chemopreventive effect is related to the high content of these foods in phytochemicals, such as polyphenols, that interfere with several processes involved in cancer progression including tumor cell growth, survival and angiogenesis. In addition to the low intake of plant-based foods, increased body mass and physical inactivity have recently emerged as other important lifestyle factors influencing cancer risk, leading to the generation of low-grade chronic inflammatory conditions which are a key process involved in tumor progression. The objectives of the current study are to investigate the inhibitory effects of these polyphenols on angiogenesis triggered by an inflammatory cytokine (IL-6) and to determine the mechanisms underlying this action. We found that, among the tested polyphenols, apigenin and luteolin were the most potent angiogenesis inhibitors through their inhibitory effect on the inflammatory cytokine IL-6/STAT3 pathway. These effects resulted in modulation of the activation of extracellular signal-regulated kinase-1/2 signaling triggered by IL-6, as well as in a marked reduction in the proliferation, migration and morphogenic differentiation of endothelial cells. Interestingly, these polyphenols also modulated the expression of IL-6 signal transducing receptor (IL-6Rα) and the secretion of the extracellular matrix degrading enzyme MMP-2 as well as the expression of suppressor of cytokine signaling (SOCS3) protein. Overall, these results may provide important new information on the role of diet in cancer prevention. Copyright © 2012 Elsevier Inc. All rights reserved.",
"title": "Diet-derived polyphenols inhibit angiogenesis by modulating the interleukin-6/STAT3 pathway."
},
{
"docid": "MED-3554",
"text": "A great deal of effort is now being devoted to the development of new drugs that hopefully will control the spread of inoperable cancer by safely inhibiting tumor-evoked angiogenesis. However, there is growing evidence that certain practical nutritional measures have the potential to slow tumor angiogenesis, and it is reasonable to anticipate that, by combining several measures that work in distinct but complementary ways to impede the angiogenic process, a clinically useful 'multifocal angiostatic therapy' (MAT) might be devised. Several measures which might reasonably be included in such a protocol are discussed below, and include: a low-fat, low-glycemic index vegan diet, which may down-regulate the systemic IGF-I activity that supports angiogenesis; supplemental omega-3-rich fish oil, which has been shown to inhibit endothelial expression of Flk-1, a functionally crucial receptor for VEGF, and also can suppress tumor production of pro-angiogenic eicosanoids; high-dose selenium, which has recently been shown to inhibit tumor production of VEGF; green tea polyphenols, which can suppress endothelial responsiveness to both VEGF and fibroblast growth factor; and high-dose glycine, whose recently reported angiostatic activity may reflect inhibition of endothelial cell mitosis, possibly mediated by activation of glycine-gated chloride channels. In light of evidence that tumor-evoked angiogenesis has a high requirement for copper, copper depletion may have exceptional potential as an angiostatic measure, and is most efficiently achieved with the copper-chelating drug tetrathiomolybdate. If logistical difficulties make it difficult to acquire this experimental drug, high-dose zinc supplementation can achieve a slower depletion of the body's copper pool, and in any case can be used as maintenance therapy to maintain an adequate level of copper depletion. A provisional protocol is offered for a nutritionally based MAT entailing a vegan diet and supplemental intakes of fish oil, selenium, green tea polyphenols, glycine, and zinc. Inasmuch as cox-2 is overexpressed in many cancers, and cAMP can boost tumor production of various angiogenic factors as well as autogenous growth factors, adjunctive use of cox-2-specific NSAIDS may be warranted in some cases.",
"title": "A wholly nutritional 'multifocal angiostatic therapy' for control of disseminated cancer."
},
{
"docid": "MED-3555",
"text": "A number of epidemiological studies have investigated associations between various phytochemicals and cancer risk. Phytoestrogens and carotenoids are the two most commonly studied classes of phytochemicals; phytosterols, isothiocyanates, and chlorophyll also have been investigated, although to a much lesser extent. Because there have been no systematic reviews of the literature on all phytochemicals and cancer risk to date, this article systematically reviews 96 published epidemiological studies that examined associations between phytochemicals and cancer risk. Most studies found null associations between individual phytochemicals and cancer risk at various sites. In addition, results from past studies have been largely inconsistent, and observed associations have been of relatively modest magnitude. The most consistent protective effects were observed for higher levels--dietary intake, serum, plasma, or urinary metabolites--of β-carotene and renal cell cancer, β-cryptoxanthin and lung cancer, isothiocyanates and lung cancer, isothiocyanates and gastrointestinal cancer, lignans and postmenopausal breast cancer, and flavonoids and lung cancer. Although elevated risk of certain cancers with higher levels of certain phytochemicals was observed, an insufficient pool of studies examining the same associations or inconsistent findings across studies limit the ability to conclude that any one phytochemical increases cancer risk. Additional research is needed to support previously identified associations in cases where only one study has examined a particular relationship. Importantly, continued research efforts are needed to evaluate the cumulative and interactive effects of numerous phytochemicals and phytochemical-rich foods on cancer risk.",
"title": "Phytochemicals and cancer risk: a review of the epidemiological evidence."
},
{
"docid": "MED-3549",
"text": "Studies have shown that fisetin, a small phytochemical molecule, has antitumor activity; however, its antiangiogenic activity has not yet been examined. Accordingly, herein, we investigated the antiangiogenic efficacy and associated mechanisms of fisetin in human umbilical vein endothelial cells (HUVECs). Fisetin (10-50 μM) strongly inhibited the regular serum plus growth supplement- and vascular endothelial growth factor (VEGF)-induced growth (up to 92%, P < 0.001) and survival (up to 16%, P < 0.001) of HUVEC in a dose- and time-dependent manner. Fisetin also caused cell cycle arrest at G(1) (strong) and G(2)/M (moderate) phases together with a decrease in cyclin D1 and an increase in p53 levels. Fisetin-caused cell death was accompanied by decreased expression of survivin and an increase in cleaved levels of caspases-3 and -7 and poly-(ADP-ribose) polymerase along with an increased ratio of Bax to Bcl-2. Furthermore, fisetin inhibited capillary-like tube formation on Matrigel (up to 85%, P < 0.001) as well as migration (up to 66%, P < 0.001), which were associated with decreased expression of endothelial nitric oxide synthase (eNOS) and VEGF in HUVEC. It also decreased the expression of eNOS, VEGF, inducible nitric oxide synthase, matrix metalloproteinase-2 and -9 in A549 and DU145 human cancer cells. In vivo matrigel plug assay in mice showed significant decrease in size (up to 43%, P < 0.001), vascularization and hemoglobin content (up to 94%, P < 0.001) in the plugs from fisetin-treated, compared with control mice. Overall, these results suggest that fisetin inhibits various attributes of angiogenesis, which might contribute to its reported antitumor effects, and therefore, fisetin warrants further investigation for its angiopreventive potential toward cancer control.",
"title": "Fisetin inhibits various attributes of angiogenesis in vitro and in vivo--implications for angioprevention."
},
{
"docid": "MED-3550",
"text": "Between 2000 and 2050, the number of new cancer patients diagnosed annually is expected to double, with an accompanying increase in treatment costs of more than $80 billion over just the next decade. Efficacious strategies for cancer prevention will therefore be vital for improving patients' quality of life and reducing healthcare costs. Judah Folkman first proposed antiangiogenesis as a strategy for preventing dormant microtumors from progressing to invasive cancer. Although antiangiogenic drugs are now available for many advanced malignancies (colorectal, lung, breast, kidney, liver, brain, thyroid, neuroendocrine, multiple myeloma, myelodysplastic syndrome), cost and toxicity considerations preclude their broad use for cancer prevention. Potent antiangiogenic molecules have now been identified in dietary sources, suggesting that a rationally designed antiangiogenic diet could provide a safe, widely available, and novel strategy for preventing cancer. This paper presents the scientific, epidemiologic, and clinical evidence supporting the role of an antiangiogenic diet for cancer prevention.",
"title": "Tumor Angiogenesis as a Target for Dietary Cancer Prevention"
},
{
"docid": "MED-3552",
"text": "The study evaluated the protective effects of purple rice (Oryza sativa L.) bran extract (PRE) and its constituents, cyanidin and peonidin, against angiogenesis induced by vascular endothelial growth factor (VEGF). The effects of VEGF and PRE were examined by in vitro tube formation assays and following 14-day co-culture of human umbilical vein endothelial cells (HUVECs) and fibroblasts. The antiangiogenic mechanism of PRE was evaluated by VEGF-induced proliferation and migration of HUVECs and/or human retinal microvascular endothelial cells (HRMECs) and phosphorylation of extracellular signal-regulated kinase (ERK) and p38. The PRE significantly suppressed VEGF-induced tube formation, proliferation and migration in HUVECs and HRMECs as well as phosphorylation of ERK and p38. Cyanidin and peonidin also suppressed the proliferation and migration induced by VEGF. These findings indicate that PRE and anthocyanidins suppress VEGF-induced angiogenesis by inhibiting proliferation and migration and suggest that the inhibition of phosphorylated-ERK and -p38 may be involved in the underlying mechanism. Copyright © 2011 John Wiley & Sons, Ltd.",
"title": "Purple rice (Oryza sativa L.) extract and its constituents inhibit VEGF-induced angiogenesis."
},
{
"docid": "MED-3551",
"text": "Breast cancer is the leading cause of cancer-related deaths for women in the United States and the rest of the world. About 8% of women develop breast cancer during the course of their lives. Dietary habits are closely associated with both the risk and progression of breast cancer. Dietary agents have accumulated increasing importance with regards to the prevention and treatment of breast cancer. One such manner by which these compounds can target breast cancer development and progression is through interference with the angiogenic pathways. Angiogenesis is an intricate process that involves the development of new capillaries from previously existing blood vessels. Disruption of this pathway, therefore, provides a novel and effective avenue for therapeutic intervention of breast cancer. Various phytochemicals found in the diet kill breast cancer cells in vitro and prevent as well as suppress breast cancer progression in various preclinical animal models. This review examines the value of dietary phytoconstituents in the prevention and treatment of breast cancer through modulation of the intricate and complex process of angiogenesis. In addition, the potential benefits, challenges, and future directions of research on anti-angiogenic dietary phytochemicals in the prevention and intervention of breast cancer are also addressed. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",
"title": "Modulation of angiogenesis by dietary phytoconstituents in the prevention and intervention of breast cancer."
}
] |
[
{
"docid": "MED-2990",
"text": "ONJ has been increasingly suspected to be a potential complication of bisphosphonate therapy in recent years. Thus, the ASBMR leadership appointed a multidisciplinary task force to address key questions related to case definition, epidemiology, risk factors, diagnostic imaging, clinical management, and future areas for research related to the disorder. This report summarizes the findings and recommendations of the task force. INTRODUCTION: The increasing recognition that use of bisphosphonates may be associated with osteonecrosis of the jaw (ONJ) led the leadership of the American Society for Bone and Mineral Research (ASBMR) to appoint a task force to address a number of key questions related to this disorder. MATERIALS AND METHODS: A multidisciplinary expert group reviewed all pertinent published data on bisphosphonate-associated ONJ. Food and Drug Administration drug adverse event reports were also reviewed. RESULTS AND CONCLUSIONS: A case definition was developed so that subsequent studies could report on the same condition. The task force defined ONJ as the presence of exposed bone in the maxillofacial region that did not heal within 8 wk after identification by a health care provider. Based on review of both published and unpublished data, the risk of ONJ associated with oral bisphosphonate therapy for osteoporosis seems to be low, estimated between 1 in 10,000 and <1 in 100,000 patient-treatment years. However, the task force recognized that information on incidence of ONJ is rapidly evolving and that the true incidence may be higher. The risk of ONJ in patients with cancer treated with high doses of intravenous bisphosphonates is clearly higher, in the range of 1-10 per 100 patients (depending on duration of therapy). In the future, improved diagnostic imaging modalities, such as optical coherence tomography or MRI combined with contrast agents and the manipulation of image planes, may identify patients at preclinical or early stages of the disease. Management is largely supportive. A research agenda aimed at filling the considerable gaps in knowledge regarding this disorder was also outlined.",
"title": "Bisphosphonate-associated osteonecrosis of the jaw: report of a task force of the American Society for Bone and Mineral Research."
},
{
"docid": "MED-5061",
"text": "Bovine leukemia virus (BLV) is an oncogenic retrovirus that commonly infects cattle and causes B cell leukosis in 1-5% of infected cattle. BLV-infected cells are present in marketed beef and dairy products. In the decade after the discovery of BLV in 1969, studies using agar gel immunodiffusion and complement fixation assays failed to find antibodies to BLV in human sera. This led to the prevailing opinion that exposure of humans to BLV and/or the potential for infection are not significant and therefore the virus is not a public health hazard. We reexamined this issue using more sensitive immunological techniques available today. Using immunoblotting to test the sera of 257 humans for antibodies of four isotypes (IgG1, IgM, IgA, and IgG4) to the BLV capsid antigen (p24), we detected at least one antibody isotype reactive with BLV in 74% of the human sera tested. The specificity of the reactivity was strongly suggested by competition studies and by ruling out cross-reacting antibodies to other chronic human viruses. Our results suggest that antibodies reactive with the BLV capsid antigen may serve as a biomarker for exposure to BLV and this exposure may be widespread. The results do not necessarily mean that humans are actually infected with BLV; the antibodies could be a response to heat-denatured BLV antigens consumed in food. They do, however, suggest that further studies in this area could be important.",
"title": "Humans have antibodies reactive with Bovine leukemia virus."
},
{
"docid": "MED-950",
"text": "BACKGROUND: The association between consumption of multivitamins and breast cancer is inconsistent in epidemiologic studies. OBJECTIVE: To perform a meta-analysis of cohort and case-control studies to evaluate multivitamin intake and its relationship with breast cancer risk. METHODS: The published literature was systematically searched and reviewed using MEDLINE (1950 through July 2010), EMBASE (1980 through July 2010), and the Cochrane Central Register of Controlled Trials (The Cochrane Library 2010 issue 1). Studies that included specific risk estimates were pooled using a random-effects model. The bias and quality of these studies were assessed with REVMAN statistical software (version 5.0) and the GRADE method of the Cochrane Collaboration. RESULTS: Eight of 27 studies that included 355,080 subjects were available for analysis. The total duration of multivitamin use in these trials ranged from 3 to 10 years. The frequency of current use in these studies ranged from 2 to 6 times/week. In analyses by duration of use 10 years or longer or 3 years or longer and by frequency 7 or more times/week that were reported in these studies, multivitamin use was not significantly associated with the risk of breast cancer. Only 1 recent Swedish cohort study concluded that multivitamin use is associated with an increased risk of breast cancer. The results of a meta-analysis that pooled data from 5 cohort studies and 3 case-control studies indicated that the overall multivariable relative risk and odds ratio were 0.10 (95% CI 0.60 to 1.63; p = 0.98) and 1.00 (95% CI 0.51 to 1.00; p = 1.00), respectively. The association was not statistically significant. CONCLUSIONS: Multivitamin use is likely not associated with a significant increased or decreased risk of breast cancer, but these results highlight the need for more case-control studies or randomized controlled clinical trials to further examine this relationship.",
"title": "Multivitamin supplement use and risk of breast cancer: a meta-analysis."
},
{
"docid": "MED-1670",
"text": "The effect of polyphenols, phenolic acids and tannins (PPTs) from strawberry and apple on uptake and apical to basolateral transport of glucose was investigated using Caco-2 intestinal cell monolayers. Substantial inhibition on both uptake and transport was observed by extracts from both strawberry and apple. Using sodium-containing (glucose transporters SGLT1 and GLUT2 both active) and sodium-free (only GLUT2 active) conditions, we show that the inhibition of GLUT2 was greater than that of SGLT1. The extracts were analyzed and some of the constituent PPTs were also tested. Quercetin-3-O-rhamnoside (IC₅₀ =31 μM), phloridzin (IC₅₀=146 μM), and 5-caffeoylquinic acid (IC₅₀=2570 μM) contributed 26, 52 and 12%, respectively, to the inhibitory activity of the apple extract, whereas pelargonidin-3-O-glucoside (IC₅₀=802 μM) contributed 26% to the total inhibition by the strawberry extract. For the strawberry extract, the inhibition of transport was non-competitive based on kinetic analysis, whereas the inhibition of cellular uptake was a mixed-type inhibition, with changes in both V(max) and apparent K(m) . The results in this assay show that some PPTs inhibit glucose transport from the intestinal lumen into cells and also the GLUT2-facilitated exit on the basolateral side. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",
"title": "Polyphenols and phenolic acids from strawberry and apple decrease glucose uptake and transport by human intestinal Caco-2 cells."
},
{
"docid": "MED-4447",
"text": "Enterolignans (enterodiol and enterolactone) can potentially reduce the risk of certain cancers and cardiovascular diseases. Enterolignans are formed by the intestinal microflora after the consumption of plant lignans. Until recently, only secoisolariciresinol and matairesinol were considered enterolignan precursors, but now several new precursors have been identified, of which lariciresinol and pinoresinol have a high degree of conversion. Quantitative data on the contents in foods of these new enterolignan precursors are not available. Thus, the aim of this study was to compile a lignan database including all four major enterolignan precursors. Liquid chromatography-tandem mass spectrometry was used to quantify lariciresinol, pinoresinol, secoisolariciresinol and matairesinol in eighty-three solid foods and twenty-six beverages commonly consumed in The Netherlands. The richest source of lignans was flaxseed (301,129 microg/100 g), which contained mainly secoisolariciresinol. Also, lignan concentrations in sesame seeds (29,331 microg/100 g, mainly pinoresinol and lariciresinol) were relatively high. For grain products, which are known to be important sources of lignan, lignan concentrations ranged from 7 to 764 microg/100 g. However, many vegetables and fruits had similar concentrations, because of the contribution of lariciresinol and pinoresinol. Brassica vegetables contained unexpectedly high levels of lignans (185-2321 microg/100 g), mainly pinoresinol and lariciresinol. Lignan levels in beverages varied from 0 (cola) to 91 microg/100 ml (red wine). Only four of the 109 foods did not contain a measurable amount of lignans, and in most cases the amount of lariciresinol and pinoresinol was larger than that of secoisolariciresinol and matairesinol. Thus, available databases largely underestimate the amount of enterolignan precursors in foods.",
"title": "Lignan contents of Dutch plant foods: a database including lariciresinol, pinoresinol, secoisolariciresinol and matairesinol."
},
{
"docid": "MED-3754",
"text": "Two hundred thirty registered nurses and seventy physicians participated in a retrospective study scrutinizing placebo effects, prescribing patterns, and staff attitudes in a university-based general hospital setting. Despite copious experimental literature devoted to placebo effects over the past thirty years, the medical and surgical use of placebos seems to disregard experimental data. Although 80% of the staff had used placebos in the hospital, their knowledge of placebo effects was in many respects deficient. Within the hospital, 89% of placebo use was directed toward the amelioration of \"pain\"; the authors believe that emphasis should be placed on the education of staff to perceive emotional, social, and physiological concomitants of pain rather than resorting to a purely physicalistic approach. A need to acknowledge staff conflicts over the ethical use of placebos should be a significant part of this educational approach.",
"title": "A survey of placebo use in a general hospital."
},
{
"docid": "MED-1934",
"text": "Objective Investigate the effects of 12 months of dietary weight loss and/or aerobic exercise on leukocyte telomere length in postmenopausal women. Design and Methods 439 overweight or obese women (50–75 y) were randomized to: i) dietary weight loss (N=118); ii) aerobic exercise (N=117), iii) diet + exercise (N=117), or iv) control (N=87). The diet intervention was a group-based program with a 10% weight loss goal. The exercise intervention was 45 mins/day, 5 days/week of moderate-to-vigorous aerobic activity. Fasting blood samples were taken at baseline and 12 months. DNA was extracted from isolated leukocytes and telomere length was measured by quantitative-polymerase chain reaction (qPCR). Mean changes were compared between groups (intent-to-treat) using generalized estimating equations. Results Baseline telomere length was inversely associated with age (r=−0.12 p<0.01) and positively associated with maximal oxygen uptake (r=0.11, p=0.03), but not with BMI or %body fat. Change in telomere length was inversely correlated with baseline telomere length (r=−0.47, p<0.0001). No significant difference in leukocyte telomere length was detected in any intervention group compared to controls, nor was the magnitude of weight loss associated with telomere length at 12 months. Conclusions Twelve-months of dietary weight loss and exercise did not change telomere length in postmenopausal women.",
"title": "Independent and Combined Effects of Dietary Weight Loss and Exercise on Leukocyte Telomere Length in Postmenopausal Women"
},
{
"docid": "MED-972",
"text": "A study is reported in which the prevalence of symptomless diverticular disease of the colon is related to the consumption of dietary fibre in vegetarians and non-vegetarians. Vegetarians had a significantly higher mean fibre intake (41.5 g/day) than non-vegetarians (21.4 g/day). Diverticular disease was commoner in non-vegetarians (33%) than in vegetarians (12%). Comparison of subjects with and without diverticular disease in the vegetarian and non-vegetarian groups provided some further evidence that a low intake of cereal fibre is associated with the presence of diverticular disease.",
"title": "Symptomless diverticular disease and intake of dietary fibre."
},
{
"docid": "MED-2793",
"text": "Piperine, a major active component of black and long peppers, has been reported to enhance drug bioavailability. The present studies were aimed at understanding the interaction of piperine with enzymatic drug biotransforming reactions in hepatic tissue in vitro and in vivo. Piperine inhibited arylhydrocarbon hydroxylation, ethylmorphine-N-demethylation, 7-ethoxycoumarin-O-deethylation and 3-hydroxy-benzo(a)pyrene glucuronidation in rat postmitochondrial supernatant in vitro in a dose-dependent manner. Piperine inhibition of these reactions in postmitochondrial supernatant from 3-methylcholanthrene- and phenobarbital-treated rats was similar to the controls. Inhibition by piperine of arylhydrocarbon hydroxylase (AHH) from 3-methylcholanthrene-treated rats was comparable to that observed with 7,8-benzoflavone. Piperine caused noncompetitive inhibition of hepatic microsomal AHH from the untreated and 3-methylcholanthrene-treated rats with a Ki of 30 microM which was close to the apparent Km of AHH observed in the controls. Similarly, the kinetics of inhibition of ethylmorphine-N-demethylase from control rat liver microsomes exhibited noncompetitive inhibition with an apparent Km of 0.8 mM and Ki of 35 microM. These studies demonstrated that piperine is a nonspecific inhibitor of drug metabolism which shows little discrimination between different cytochrome P-450 forms. Oral administration of piperine in rats strongly inhibited the hepatic AHH and UDP-glucuronyltransferase activities. The maximal inhibition of AHH observed within 1 hr restored to normal value in 6 hr. Pretreatment with piperine prolonged hexobarbital sleeping time and zoxazolamine paralysis time in mice at half the dose of SKF-525A. These results demonstrate that piperine is a potent inhibitor of drug metabolism.",
"title": "Biochemical basis of enhanced drug bioavailability by piperine: evidence that piperine is a potent inhibitor of drug metabolism."
},
{
"docid": "MED-980",
"text": "Background An increased rate of brain atrophy is often observed in older subjects, in particular those who suffer from cognitive decline. Homocysteine is a risk factor for brain atrophy, cognitive impairment and dementia. Plasma concentrations of homocysteine can be lowered by dietary administration of B vitamins. Objective To determine whether supplementation with B vitamins that lower levels of plasma total homocysteine can slow the rate of brain atrophy in subjects with mild cognitive impairment in a randomised controlled trial (VITACOG, ISRCTN 94410159). Methods and Findings Single-center, randomized, double-blind controlled trial of high-dose folic acid, vitamins B6 and B12 in 271 individuals (of 646 screened) over 70 y old with mild cognitive impairment. A subset (187) volunteered to have cranial MRI scans at the start and finish of the study. Participants were randomly assigned to two groups of equal size, one treated with folic acid (0.8 mg/d), vitamin B12 (0.5 mg/d) and vitamin B6 (20 mg/d), the other with placebo; treatment was for 24 months. The main outcome measure was the change in the rate of atrophy of the whole brain assessed by serial volumetric MRI scans. Results A total of 168 participants (85 in active treatment group; 83 receiving placebo) completed the MRI section of the trial. The mean rate of brain atrophy per year was 0.76% [95% CI, 0.63–0.90] in the active treatment group and 1.08% [0.94–1.22] in the placebo group (P = 0.001). The treatment response was related to baseline homocysteine levels: the rate of atrophy in participants with homocysteine >13 µmol/L was 53% lower in the active treatment group (P = 0.001). A greater rate of atrophy was associated with a lower final cognitive test scores. There was no difference in serious adverse events according to treatment category. Conclusions and Significance The accelerated rate of brain atrophy in elderly with mild cognitive impairment can be slowed by treatment with homocysteine-lowering B vitamins. Sixteen percent of those over 70 y old have mild cognitive impairment and half of these develop Alzheimer's disease. Since accelerated brain atrophy is a characteristic of subjects with mild cognitive impairment who convert to Alzheimer's disease, trials are needed to see if the same treatment will delay the development of Alzheimer's disease. Trial Registration Controlled-Trials.com ISRCTN94410159",
"title": "Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial"
},
{
"docid": "MED-1355",
"text": "Depression and anxiety are the most common psychiatric conditions seen in the general medical setting, affecting millions of individuals in the United States. The treatments for depression and anxiety are multiple and have varying degrees of effectiveness. Physical activity has been shown to be associated with decreased symptoms of depression and anxiety. Physical activity has been consistently shown to be associated with improved physical health, life satisfaction, cognitive functioning, and psychological well-being. Conversely, physical inactivity appears to be associated with the development of psychological disorders. Specific studies support the use of exercise as a treatment for depression. Exercise compares favorably to antidepressant medications as a first-line treatment for mild to moderate depression and has also been shown to improve depressive symptoms when used as an adjunct to medications. While not as extensively studied, exercise has been shown to be an effective and cost-efficient treatment alternative for a variety of anxiety disorders. While effective, exercise has not been shown to reduce anxiety to the level achieved by psychopharmaceuticals.",
"title": "Exercise for the treatment of depression and anxiety."
},
{
"docid": "MED-1371",
"text": "Epidemiological evidence suggests that the Mediterranean diet (MD) could reduce the risk of breast cancer (BC). As evidence from the prospective studies remains scarce and conflicting, we investigated the association between adherence to the MD and risk of BC among 335,062 women recruited from 1992 to 2000, in ten European countries, and followed for 11 years on average. Adherence to the MD was estimated through an adapted relative Mediterranean diet (arMED) score excluding alcohol. Cox proportional hazards regression models were used while adjusting for BC risk factors. A total of 9,009 postmenopausal and 1,216 premenopausal first primary incident invasive BC were identified (5,862 estrogen or progesterone receptor positive [ER+/PR+] and 1,018 estrogen and progesterone receptor negative [ER-/PR-]). The arMED was inversely associated with the risk of BC overall and in postmenopausal women (high vs. low arMED score; hazard ratio [HR] = 0.94 [95% confidence interval [CI]: 0.88, 1.00] ptrend = 0.048, and HR = 0.93 [95% CI: 0.87, 0.99] ptrend = 0.037, respectively). The association was more pronounced in ER-/PR- tumors (HR = 0.80 [95% CI: 0.65, 0.99] ptrend = 0.043). The arMED score was not associated with BC in premenopausal women. Our findings show that adherence to a MD excluding alcohol was related to a modest reduced risk of BC in postmenopausal women, and this association was stronger in receptor-negative tumors. The results support the potential scope for BC prevention through dietary modification. Copyright © 2012 UICC.",
"title": "Adherence to the mediterranean diet and risk of breast cancer in the European prospective investigation into cancer and nutrition cohort study."
},
{
"docid": "MED-2774",
"text": "Concern has been expressed about the fact that cows' milk contains estrogens and could stimulate the growth of hormone-sensitive tumors. In this study, organic cows' milk and two commercial substitutes were digested in vitro and tested for their effects on the growth of cultures of prostate and breast cancer cells. Cows' milk stimulated the growth of LNCaP prostate cancer cells in each of 14 separate experiments, producing an average increase in growth rate of over 30%. In contrast, almond milk suppressed the growth of these cells by over 30%. Neither cows' milk nor almond milk affected the growth of MCF-7 breast cancer cells or AsPC-1 pancreatic cancer cells significantly. Soy milk increased the growth rate of the breast cancer cells. These data indicate that prostate and breast cancer patients should be cautioned about the possible promotional effects of commercial dairy products and their substitutes.",
"title": "Milk stimulates growth of prostate cancer cells in culture."
},
{
"docid": "MED-5256",
"text": "Probably due to caffeine-induced gastric acid secretion, negative effects of coffee upon various upper-gastrointestinal diseases have been precariously accepted, despite the inadequate epidemiological evidence. Our aim is to evaluate the effect of coffee consumption on four major acid-related diseases: gastric ulcer (GU), duodenal ulcer (DU), reflux esophagitis (RE), and non-erosive reflux disease (NERD) based on the large-scale multivariate analysis. Of the 9,517 healthy adults, GU, DU, and RE were diagnosed by endoscopy, and NERD was diagnosed by the symptoms of heartburn and regurgitation without esophageal erosion. Associations between coffee consumption and the four disorders were evaluated, together with age, gender, body mass index (BMI), Helicobacter pylori (HP) infection status, pepsinogen I/II ratio, smoking, and alcohol. We further performed meta-analysis using the random effects model to redefine the relationship between coffee intake and peptic ulcer disease. The eligible 8,013 study subjects comprised of 5,451 coffee drinkers and 2,562 non-coffee drinkers. By univariate analysis, age, BMI, pepsinogen I/II ratio, smoking, and alcohol showed significant associations with coffee consumption. By multiple logistic regression analysis, positively correlated factors with significance were HP infection, current smoking, BMI, and pepsinogen I/II ratio for GU; HP infection, pepsinogen I/II ratio, and current smoking for DU; HP non-infection, male, BMI, pepsinogen I/II ratio, smoking, age, and alcohol for RE; younger age, smoking, and female for NERD. The meta-analyses could detect any association of coffee consumption with neither GU nor DU. In conclusion, there are no significant relationship between coffee consumption and the four major acid-related upper gastrointestinal disorders.",
"title": "No Association of Coffee Consumption with Gastric Ulcer, Duodenal Ulcer, Reflux Esophagitis, and Non-Erosive Reflux Disease: A Cross-Sectional Study of 8,013 Healthy Subjects in Japan"
},
{
"docid": "MED-1858",
"text": "As a hard tissue dental disease, dental erosion has a multifactorial etiology. The majority of dental erosion that originates from extrinsic sources is the result of dietary intake, particularly acidic beverages. Several preventive means have been proposed to minimize the damage to the dentition, including a reduction in the consumption of causative beverages and the adoption of a specific method of drinking, utilizing a straw instead of a cup. This article presents two cases involving the clinical and radiographic features of erosion lesions associated with chronic and excessive intake of acidic carbonated beverages. These examples embody how drinking patterns influence the formation of erosion lesions in various anatomic locations within the dentition. The clinical and radiographic evidence presented in this report cautions against the use of nonspecific terms, such as \"cup versus straw,\" and instead suggests implementing a more precise description of the suggested method. In view of the extensive damage inflicted by the chronic, excessive intake of carbonated beverages, preventive measures are considered to be the only effective course of management. This article offers illustrative examples of erosion lesions associated with long-term excessive intake of carbonated beverages. The influence of the drinking method--that is, a straw positioned into the labial vestibule versus a cup--on the anatomic location of the erosion lesions will be demonstrated through clinical and radiographic evidence.",
"title": "Influence of drinking patterns of carbonated beverages on dental erosion."
},
{
"docid": "MED-1237",
"text": "It has become widely accepted that Type 2 diabetes is inevitably life-long, with irreversible and progressive beta cell damage. However, the restoration of normal glucose metabolism within days after bariatric surgery in the majority of people with Type 2 diabetes disproves this concept. There is now no doubt that this reversal of diabetes depends upon the sudden and profound decrease in food intake, and does not relate to any direct surgical effect. The Counterpoint study demonstrated that normal glucose levels and normal beta cell function could be restored by a very low calorie diet alone. Novel magnetic resonance methods were applied to measure intra-organ fat. The results showed two different time courses: a) resolution of hepatic insulin sensitivity within days along with a rapid fall in liver fat and normalisation of fasting glucose levels; and b) return of normal beta cell insulin secretion over weeks in step with a fall in pancreas fat. Now that it has been possible to observe the pathophysiological events during reversal of Type 2 diabetes, the reverse time course of events which determine the onset of the condition can be identified. The twin cycle hypothesis postulates that chronic calorie excess leads to accumulation of liver fat with eventual spill over into the pancreas. These self-reinforcing cycles between liver and pancreas eventually cause metabolic inhibition of insulin secretion after meals and onset of hyperglycaemia. It is now clear that Type 2 diabetes is a reversible condition of intra-organ fat excess to which some people are more susceptible than others.",
"title": "Banting Memorial Lecture 2012 Reversing the twin cycles of Type 2 diabetes"
},
{
"docid": "MED-1593",
"text": "OBJECTIVE: Based on the hypothesis that high-meat diets may increase breast cancer risk through hormonal pathways, the present analysis compared oestrogens in serum and urine by meat-eating status. DESIGN: Intervention with repeated measures. SETTING: Two randomized soya trials (BEAN1 and BEAN2) among premenopausal healthy women. SUBJECTS: BEAN1 participants completed seven unannounced 24 h dietary recalls and donated five blood and urine samples over 2 years. BEAN2 women provided seven recalls and three samples over 13 months. Serum samples were analysed for oestrone (E₁) and oestradiol (E₂) using RIA. Nine oestrogen metabolites were measured in urine by LC-MS. Semi-vegetarians included women who reported consuming <30 g of red meat, poultry and fish daily, and pescatarians those who reported consuming <20 g of meat/poultry but >10 g of fish daily. All other women were classified as non-vegetarians. We applied mixed models to compute least-square means by vegetarian status adjusted for potential confounders. RESULTS: The mean age of the 272 participants was 41·9 (SD 4·5) years. Serum E₁ (85 v. 100 pg/ml, P = 0·04) and E₂ (140 v. 154 pg/ml, P = 0·04) levels were lower in the thirty-seven semi-vegetarians than in the 235 non-vegetarians. The sum of the nine urinary oestrogen metabolites (183 v. 200 pmol/mg creatinine, P = 0·27) and the proportions of individual oestrogens and pathways did not differ by meat-eating status. Restricting the models to the samples collected during the luteal phase strengthened the associations. CONCLUSIONS: Given the limitations of the study, the lower levels of serum oestrogens in semi-vegetarians than non-vegetarians need confirmation in larger populations.",
"title": "Oestrogen levels in serum and urine of premenopausal women eating low and high amounts of meat."
},
{
"docid": "MED-3030",
"text": "Consumption of marine fish provides both benefits (lean protein, omega-3 fatty acids and essential nutrients) and risks (main source of mercury (Hg) exposure for humans). Mercury is a potent neurotoxin and the source of more fish advisories nationwide than any other toxicant. Despite the widespread nature of Hg, it is unknown whether local Hg contamination reflects national and regional levels often used as bases to inform consumers of potential fish consumption risk. Thus, the objectives of our study were to examine Hg levels of six commonly consumed marine species harvested locally off the North Carolina coast and to compare our results to published regional (Monterey Bay Aquarium's Seafood Watch List) and national (Environmental Protection Agency, EPA, and Food and Drug Administration, FDA) Hg averages, action levels, and guidelines. We found significant differences in Hg concentrations among collected species, and we identified correlations between Hg concentration and fish length and trophic levels. Collected mahi mahi and triggerfish were below the EPA fish tissue action level (0.3ppm). Wahoo and grouper exceeded the EPA action level but were below the FDA action level (1.0ppm). King mackerel had the highest Hg concentration among targeted species, exceeding both EPA and FDA action levels. Further, our local results were not always consistent with calculated averages from EPA and FDA databases for the same species, and although many of our findings were consistent with Monterey Bay Aquarium's Seafood Watch List (southeast region), recommendations based on Hg levels would conflict with recommendations they provide based on sustainability. We find regional and national averages are not always reflective of local Hg contamination and suggest local data may be needed to accurately assess consumer risk.",
"title": "Do national advisories serve local consumers: an assessment of mercury in economically important North Carolina fish."
},
{
"docid": "MED-5301",
"text": "Background The US diet is high in salt, with the majority coming from processed foods. Reducing dietary salt is an important potential public health target. Methods We used the Coronary Heart Disease (CHD) Policy Model to quantify the benefits of potentially achievable population-wide reductions in dietary salt of up to 3 gm/day (1200 mg/day of sodium). We estimated cardiovascular disease rates and costs in age, sex, and race subgroups, compared salt reduction with other interventions to reduce cardiovascular risk, and determined the cost-effectiveness of salt reduction compared with drug treatment of hypertension. Results Reducing salt by 3 gm/day is projected to result in 60,000–120,000 fewer new CHD cases, 32,000–66,000 fewer new strokes, 54,000–99,000 fewer myocardial infarctions, and 44,000–92,000 fewer deaths from any cause annually. All segments of the population would benefit, with blacks benefiting proportionately more, women benefiting particularly from stroke reduction, older adults from reductions in CHD events, and younger adults from lower mortality rates. The cardiovascular benefits from lower salt are on par with benefits from reducing tobacco, obesity, or cholesterol. A regulatory intervention designed to achieve 3 gm/day salt reduction would save 194,000–392,000 quality-adjusted life-years and $10–24 billion in healthcare costs annually. Such an intervention would be cost-saving even if only a modest 1 gm/day reduction were achieved gradually over the decade from 2010–2019 and would be more cost-effective than treating all hypertensive individuals with medications. Conclusions Modest reduction in dietary salt could substantially reduce cardiovascular events and medical costs and should be a public health target.",
"title": "Reductions in Cardiovascular Disease Projected from Modest Reductions in Dietary Salt"
},
{
"docid": "MED-3892",
"text": "Mathematical models that estimate the proportion of foodborne illnesses attributable to food commodities at specific points in the food chain may be useful to risk managers and policy makers to formulate public health goals, prioritize interventions, and document the effectiveness of mitigations aimed at reducing illness. Using human surveillance data on laboratory-confirmed Salmonella infections from the Centers for Disease Control and Prevention and Salmonella testing data from U.S. Department of Agriculture Food Safety and Inspection Service's regulatory programs, we developed a point-of-processing foodborne illness attribution model by adapting the Hald Salmonella Bayesian source attribution model. Key model outputs include estimates of the relative proportions of domestically acquired sporadic human Salmonella infections resulting from contamination of raw meat, poultry, and egg products processed in the United States from 1998 through 2003. The current model estimates the relative contribution of chicken (48%), ground beef (28%), turkey (17%), egg products (6%), intact beef (1%), and pork (<1%) across 109 Salmonella serotypes found in food commodities at point of processing. While interpretation of the attribution estimates is constrained by data inputs, the adapted model shows promise and may serve as a basis for a common approach to attribution of human salmonellosis and food safety decision-making in more than one country.",
"title": "Application of Bayesian Techniques to Model the Burden of Human Salmonellosis Attributable to U.S. Food Commodities at the Point of Processing: Adaptation of a Danish Model"
},
{
"docid": "MED-5132",
"text": "Vitamin B12 deficiency anemia may have psychiatric manifestations preceding the hematological symptoms. Although a variety of symptoms are described, there are only sparse data on the role of vitamin B12 in depression. We report a case of vitamin B12 deficiency presenting with recurrent episodes of depression.",
"title": "Role of vitamin B12 in depressive disorder--a case report."
},
{
"docid": "MED-3157",
"text": "Vitamin C is an essential component of the diet and may reduce the adverse effects of exercise-induced reactive oxygen species, including muscle damage, immune dysfunction, and fatigue. However, reactive oxygen species may mediate beneficial training adaptations that vitamin C attenuates; indeed, from a total of 12 studies, vitamin C in doses >1 g·d(-1) impaired sport performance substantially in four of four studies, possibly by reducing mitochondrial biogenesis, while a further four studies demonstrated impairments that were not statistically significant. Doses of ∼0.2 g·d(-1) of vitamin C consumed through five or more servings of fruit and vegetables may be sufficient to reduce oxidative stress and provide other health benefits without impairing training adaptations.",
"title": "Effect of vitamin C supplements on physical performance."
},
{
"docid": "MED-4811",
"text": "Many deep-sea fishes store large amounts of wax esters in their body for buoyancy control. Some of them are frequently caught as by-catch of tuna and other fishes. The most noteworthy ones include escolar and oilfish. The accumulation of the indigestible wax esters in the rectum through consumption of these fish engenders discharges or leakage per rectum as orange or brownish green oil, but without noticeable loss of water. This physiological response is called keriorrhea, which is variously described as \"oily diarrhea,\" \"oily orange diarrhea,\" or \"orange oily leakage\" by the mass media and bloggers on the internet. Outbreaks of keriorrhea have been repeatedly reported across continents. Additional symptoms including nausea, vomiting, abdominal cramps, and diarrhea were complained by the victims. They are probably due to anxiety or panic when suffering from keriorrhea. Escolar and oilfish are banned from import and sale in Italy, Japan, and South Korea. Rapid detection of the two fishes is imperative to ensure proper labeling and safeguarding of the public before and after any keriorrhea outbreak.",
"title": "Fish-induced keriorrhea."
},
{
"docid": "MED-2452",
"text": "A role for diet in the pathophysiology of asthma may be mediated by altered immune or antioxidant activity with consequent effects on airway inflammation. We evaluated associations between several dietary factors assessed by a semiquantitative food frequency questionnaire, and incidence of asthma over a 10-yr period in 77,866 women 34 to 68 yr of age. Women in the highest quintile of vitamin E intake from diet, but not from supplements, had a risk of 0.53 (95% confidence interval [CI] = 0.33 to 0.86) compared with women in the lowest quintile. This relationship, however, was attenuated when the contribution from nuts, a major source of vitamin E in these data and a possible allergen, was removed (relative risk = 0.74 [0.50 to 1.10], p for trend = 0.007). Positive associations were found for vitamins C and E from supplements, but appeared to be explained by women at high risk of asthma initiating use of vitamin supplements prior to diagnosis. A nonsignificant inverse association with carotene intake was noted, but no clear relations with asthma were demonstrated for intake of linoleic acid or omega-3 fatty acids. These data suggest that antioxidant supplementation and intake of various fats during adulthood are not important determinants of asthma, although vitamin E from diet may have a modest protective effect.",
"title": "A prospective study of diet and adult-onset asthma."
},
{
"docid": "MED-2044",
"text": "Cancer incidence increases with advancing age. Over 60% of new cancers and 70% of cancer deaths occur in individuals aged 65 years or older. One factor that may contribute to this is immunosenescence - a canopy term that is used to describe age-related declines in the normal functioning of the immune system. There are multiple age-related deficits in both the innate and adaptive systems that may play a role in the increased incidence of cancer. These include decreased NK-cell function, impaired antigen uptake and presentation by monocytes and dendritic cells, an increase in 'inflammaging', a decline in the number of naïve T-cells able to respond to evolving tumor cells, and an increase in functionally exhausted senescent cells. There is consensus that habitual physical exercise can offer protection against certain types of cancer; however the evidence linking immunological mechanisms, exercise, and reduced cancer risk remain tentative. Multiple studies published over the last two decades suggest that exercise can mitigate the deleterious effects of age on immune function, thus increasing anti-cancer immunity. The potential ameliorative effect of exercise on these mechanisms include evidence that physical activity is able to stimulate greater NK-cell activity, enhance antigen-presentation, reduce inflammation, and prevent senescent cell accumulation in the elderly. Here we discuss the role played by the immune system in preventing and controlling cancer and how aging may retard these anti-cancer mechanisms. We also propose a pathway by which exercise-induced alterations in immunosenescence may decrease the incidence of cancer and help improve prognosis in cancer patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.",
"title": "Can exercise-related improvements in immunity influence cancer prevention and prognosis in the elderly?"
},
{
"docid": "MED-3853",
"text": "PURPOSE: Lignans--plant-derived compounds with estrogen-dependent and -independent anticarcinogenic properties--have been associated with postmenopausal breast cancer risk, but data are limited regarding their effect on survival. Dietary lignans are metabolized to enterolignans, which are subsequently absorbed and become bioavailable. PATIENTS AND METHODS: We assessed the prognosis of 1,140 postmenopausal patients with breast cancer age 50 to 74 years who were diagnosed between 2002 and 2005. Vital status through the end of 2009 was ascertained via local population registries, and deaths were verified by death certificates. Information on recurrences and secondary tumors was verified by clinical records and attending physicians. Associations of postdiagnostic serum enterolactone (a biomarker for dietary lignans) with overall survival and distant disease-free survival were assessed by using Cox proportional hazards models stratified by age at diagnosis and adjusted for prognostic factors. RESULTS: Median enterolactone levels for deceased patients and those still alive were 17.0 and 21.4 nmol/L, respectively. During a median of 6.1 years of follow-up after diagnosis, 162 deaths were confirmed. Higher serum enterolactone levels were associated with significantly reduced hazard ratios (HRs) for death (HR per 10 nmol/L increment, 0.94; P = .04; HR for the highest quartile, 0.58; 95% CI, 0.34 to 0.99). For distant disease, HR was 0.94 per 10 nmol/L increment (P = .08) and 0.62 (95% CI, 0.35 to 1.09) for the highest quartile. The highest quartile of serum enterolactone was associated with a significantly reduced risk of death only for estrogen receptor-negative tumors (HR, 0.27; 95% CI, 0.08 to 0.87) but not for estrogen receptor-positive tumors (HR, 0.91; 95% CI, 0.45 to 1.84: P for heterogeneity = .09). CONCLUSION: Postmenopausal patients with breast cancer who have high serum enterolactone levels may have better survival.",
"title": "Serum enterolactone and prognosis of postmenopausal breast cancer."
},
{
"docid": "MED-3986",
"text": "BACKGROUND/OBJECTIVES: Mushrooms contain very little or any vitamin D(2) but are abundant in ergosterol, which can be converted into vitamin D(2) by ultraviolet (UV) irradiation. Our objective was to investigate the bioavailability of vitamin D(2) from vitamin D(2)-enhanced mushrooms by UV-B in humans, and comparing it with a vitamin D(2) supplement. SUBJECTS/METHODS: Fresh mushrooms were irradiated with an UV-B dose of 1.5 J/cm(2), increasing vitamin D(2) content from <1 to 491 μg/100 g and made to an experimental soup. In this 5-week, single-blinded, randomized, placebo-controlled trial, 26 young subjects with serum 25-hydroxyvitamin D (25OHD) ≤ 50 nmol/l were randomly assigned into three groups ((a) mushroom, (b) supplement and (c) placebo). They received during winter (a) 28,000 IU (700 μg) vitamin D(2) via the experimental soup, or (b) 28,000 IU vitamin D(2) via a supplement or (c) placebo, respectively. RESULTS: After 2 weeks, serum 25OHD was significantly higher in the mushroom than in the placebo group (P=0.001). The serum 25OHD concentrations in the mushroom and supplement groups rose significantly and similarly over the study period by 3.9 nmol/l (95% confidence interval (95% CI): 2.9, 4.8) and by 4.7 nmol/l per week (95% CI: 3.8, 5.7), respectively. CONCLUSIONS: We are the first to demonstrate in humans that the bioavailability of vitamin D(2) from vitamin D(2)-enhanced button mushrooms via UV-B irradiation was effective in improving vitamin D status and not different to a vitamin D(2) supplement. This trial was registered at http://germanctr.de as DRKS00000195.",
"title": "Bioavailability of vitamin D₂ from UV-B-irradiated button mushrooms in healthy adults deficient in serum 25-hydroxyvitamin D: a randomized controll..."
},
{
"docid": "MED-822",
"text": "Polycystic ovary syndrome (PCOS), defined as the combination of oligoanovulation and hyperandrogenism, affects more than 5% of women of reproductive age. Insulin resistance and hyperinsulinemia appear to play an important role in its pathogenesis. Here, we will present a characterization of a PCOS cohort from North Rhine-Westphalia in Germany. Clinical features, family history as well as endocrine and metabolic parameters were prospectively recorded from 200 successive patients. All patients were evaluated for insulin resistance and beta-cell-function by oral glucose tolerance test. Patient data were compared with those of 98 age-matched control women. PCOS patients showed significantly higher BMI, body fat mass and androgen levels as well as impaired glucose and insulin metabolism. A positive family history of PCOS and diabetes was more frequent in PCOS patients. Insulin resistance (71%) was the most common metabolic abnormality in PCOS patients followed by obesity (52%) and dyslipidemia (46.3%), with an incidence of 31.5% for the metabolic syndrome. C-reactive protein and other cardiovascular risk factors were frequently elevated even in young PCOS patients. While the clinical characteristics and endocrine parameters of this German PCOS cohort were heterogeneous, they were comparable to those from other Caucasian populations.",
"title": "Clinical and biochemical characterization of women with polycystic ovary syndrome in North Rhine-Westphalia."
},
{
"docid": "MED-1413",
"text": "The human oro-gastrointestinal (GI) tract is a complex system, consisting of oral cavity, pharynx, oesophagus, stomach, small intestine, large intestine, rectum and anus, which all together with the accessory digestive organs constitute the digestive system. The function of the digestive system is to break down dietary constituents into small molecules and then absorb these for subsequent distribution throughout the body. Besides digestion and carbohydrate metabolism, the indigenous microbiota has an important influence on host physiological, nutritional and immunological processes, and commensal bacteria are able to modulate the expression of host genes that regulate diverse and fundamental physiological functions. The main external factors that can affect the composition of the microbial community in generally healthy adults include major dietary changes and antibiotic therapy. Changes in some selected bacterial groups have been observed due to controlled changes to the normal diet e.g. high-protein diet, high-fat diet, prebiotics, probiotics and polyphenols. More specifically, changes in the type and quantity of non-digestible carbohydrates in the human diet influence both the metabolic products formed in the lower regions of the GI tract and the bacterial populations detected in faeces. The interactions between dietary factors, gut microbiota and host metabolism are increasingly demonstrated to be important for maintaining homeostasis and health. Therefore the aim of this review is to summarise the effect of diet, and especially dietary interventions, on the human gut microbiota. Furthermore, the most important confounding factors (methodologies used and intrinsic human factors) in relation to gut microbiota analyses are elucidated.",
"title": "Human gut microbiota: does diet matter?"
},
{
"docid": "MED-5280",
"text": "BACKGROUND: Hypertriglyceridemia is now accepted as a risk factor for coronary heart disease, although the mechanism behind the increased risk is not well understood. The present study was undertaken to investigate the effects of triglyceridemia on endothelial function, because impaired endothelial function is considered a marker of atherogenesis. METHODS AND RESULTS: Flow- and nitroglycerin-induced dilatation of the brachial artery was investigated noninvasively by high-resolution ultrasound technique in seven young, healthy men without risk factors for coronary heart disease. Transient triglyceridemia was induced by infusion of a triglyceride emulsion, Intralipid, which raised free fatty acid concentrations twofold and triglyceride levels fourfold. Flow-induced vasodilatation decreased from 7.1+/-3.0% to 1.6+/-2.6% (P<.0002), whereas nitroglycerin-induced vasodilatation decreased from 20.5+/-5.8% to 11.5+/-3.2% (P<.002) before and after 1 hour of infusion of Intralipid, respectively. CONCLUSIONS: Transient triglyceridemia decreases vascular reactivity, presumably by both endothelium-dependent and endothelium-independent mechanisms.",
"title": "Transient triglyceridemia decreases vascular reactivity in young, healthy men without risk factors for coronary heart disease."
}
] |
1101
|
Stiff substrates encourage mesodermal differentiation by degrading beta-catenin in an integrin-dependent manner.
|
[
{
"docid": "3874000",
"text": "Regenerative medicine is predicated on understanding the mechanisms regulating development and applying these conditions to direct stem cell fate. Embryogenesis is guided by cell-cell and cell-matrix interactions, but it is unclear how these physical cues influence stem cells in culture. We used human embryonic stem cells (hESCs) to examine whether mechanical features of the extracellular microenvironment could differentially modulate mesoderm specification. We found that, on a hydrogel-based compliant matrix, hESCs accumulate β-catenin at cell-cell adhesions and show enhanced Wnt-dependent mesoderm differentiation. Mechanistically, Src-driven ubiquitination of E-cadherin by Cbl-like ubiquitin ligase releases P120-catenin to facilitate transcriptional activity of β-catenin, which initiates and reinforces mesoderm differentiation. By contrast, on a stiff hydrogel matrix, hESCs show elevated integrin-dependent GSK3 and Src activity that promotes β-catenin degradation and inhibits differentiation. Thus, we found that mechanical features of the microenvironmental matrix influence tissue-specific differentiation of hESCs by altering the cellular response to morphogens.",
"title": "Tissue Mechanics Orchestrate Wnt-Dependent Human Embryonic Stem Cell Differentiation."
}
] |
[
{
"docid": "43661837",
"text": "The canonical Wnt/beta-catenin signaling has remarkably diverse roles in embryonic development, stem cell self-renewal and cancer progression. Here, we show that stabilized expression of beta-catenin perturbed human embryonic stem (hES)-cell self-renewal, such that up to 80% of the hES cells developed into the primitive streak (PS)/mesoderm progenitors, reminiscent of early mammalian embryogenesis. The formation of the PS/mesoderm progenitors essentially depended on the cooperative action of beta-catenin together with Activin/Nodal and BMP signaling pathways. Intriguingly, blockade of BMP signaling completely abolished mesoderm generation, and induced a cell fate change towards the anterior PS progenitors. The PI3-kinase/Akt, but not MAPK, signaling pathway had a crucial role in the anterior PS specification, at least in part, by enhancing beta-catenin stability. In addition, Activin/Nodal and Wnt/beta-catenin signaling synergistically induced the generation and specification of the anterior PS/endoderm. Taken together, our findings clearly demonstrate that the orchestrated balance of Activin/Nodal and BMP signaling defines the cell fate of the nascent PS induced by canonical Wnt/beta-catenin signaling in hES cells.",
"title": "Defining early lineage specification of human embryonic stem cells by the orchestrated balance of canonical Wnt/beta-catenin, Activin/Nodal and BMP signaling."
},
{
"docid": "13779605",
"text": "There is mounting evidence that tumors are initiated by a rare subset of cells called cancer stem cells (CSCs). CSCs are generally quiescent, self-renew, form tumors at low numbers, and give rise to the heterogeneous cell types found within a tumor. CSCs isolated from multiple tumor types differentiate both in vivo and in vitro when cultured in serum, yet the factors responsible for their differentiation have not yet been identified. Here we show that vitronectin is the component of human serum driving stem cell differentiation through an integrin alpha V beta 3-dependent mechanism. CSCs cultured on vitronectin result in downregulation of stem cell genes, modulation of differentiation markers, and loss of beta-catenin nuclear localization. Blocking integrin alpha V beta 3 inhibits differentiation and subsequently tumor formation. Thus, CSCs must be engaged by one or more extracellular signals to differentiate and initiate tumor formation, defining a new axis for future novel therapies aimed at both the extrinsic and intracellular pathways.",
"title": "Identification of vitronectin as an extrinsic inducer of cancer stem cell differentiation and tumor formation."
},
{
"docid": "1782201",
"text": "Integrins regulate adhesion-dependent growth, survival and invasion of tumor cells. In particular, expression of integrin alpha(v)beta(3) is associated with progression of a variety of human tumors. Here we reveal a previously undescribed adhesion-independent role for integrin alpha(v)beta(3) in pancreatic cancer and other carcinomas. Specifically, alpha(v)beta(3) expressed in carcinoma cells enhanced anchorage-independent tumor growth in vitro and increased lymph node metastases in vivo. These effects required recruitment of c-Src to the beta(3) integrin cytoplasmic tail, leading to c-Src activation, Crk-associated substrate (CAS) phosphorylation and tumor cell survival that, unexpectedly, was independent of cell adhesion or focal adhesion kinase (FAK) activation. Pharmacological blockade of c-Src kinase activity or decreased expression of endogenous alpha(v)beta(3) integrin or c-Src not only inhibited anchorage-independent growth but also suppressed metastasis in vivo, yet these manipulations did not affect tumor cell migration or invasion. These data define an unexpected role for an integrin as a mediator of anchorage independence, suggesting that an alpha(v)beta(3)-c-Src signaling module may account for the aggressive behavior of integrin alpha(v)beta(3)-expressing tumors in humans.",
"title": "Integrin αvβ3/c-src “Oncogenic Unit” Promotes Anchorage-independence and Tumor Progression"
},
{
"docid": "21564598",
"text": "Periostin (Postn) is a matricellular protein preferentially expressed by osteocytes and periosteal osteoblasts in response to mechanical stimulation and parathyroid hormone (PTH). Whether and how periostin expression influences bone anabolism, however, remains unknown. We investigated the skeletal response of adult Postn(-/-) and Postn(+/+) mice to intermittent PTH. Compared with Postn(+/+), Postn(-/-) mice had a lower bone mass, cortical bone volume, and strength response to PTH. PTH-stimulated bone-forming indices were all significantly lower in Postn(-/-) mice, particularly at the periosteum. Furthermore, in vivo stimulation of Wnt-β-catenin signaling by PTH, as evaluated in TOPGAL reporter mice, was inhibited in the absence of periostin (TOPGAL;Postn(-/-) mice). PTH stimulated periostin and inhibited MEF2C and sclerostin (Sost) expression in bone and osteoblasts in vitro. Recombinant periostin also suppressed Sost expression, which was mediated through the integrin αVβ3 receptor, whereas periostin-blocking antibody prevented inhibition of MEF2C and Sost by PTH. In turn, administration of a Sost-blocking antiboby partially restored the PTH-mediated increase in bone mass in Postn(-/-) mice. In addition, primary osteoblasts from Postn(-/-) mice showed a lower proliferation, mineralization, and migration, both spontaneously and in response to PTH. Osteoblastic gene expression levels confirmed a defect of Postn(-/-) osteoblast differentiation with and without PTH, as well as an increased osteoblast apoptosis in the absence of periostin. These data elucidate the complex role of periostin on bone anabolism, through the regulation of Sost, Wnt-β-catenin signaling, and osteoblast differentiation.",
"title": "Regulation of beta catenin signaling and parathyroid hormone anabolic effects in bone by the matricellular protein periostin."
},
{
"docid": "2060137",
"text": "Cell-to-cell adhesions are crucial in maintaining the structural and functional integrity of cardiac cells. Little is known about the mechanosensitivity and mechanotransduction of cell-to-cell interactions. Most studies of cardiac mechanotransduction and myofibrillogenesis have focused on cell-extracellular matrix (ECM)-specific interactions. This study assesses the direct role of intercellular adhesion, specifically that of N-cadherin-mediated mechanotransduction, on the morphology and internal organization of neonatal ventricular cardiac myocytes. The results show that cadherin-mediated cell attachments are capable of eliciting a cytoskeletal network response similar to that of integrin-mediated force response and transmission, affecting myofibrillar organization, myocyte shape, and cortical stiffness. Traction forces mediated by N-cadherin were shown to be comparable to those sustained by ECM. The directional changes in predicted traction forces as a function of imposed loads (gel stiffness) provide the added evidence that N-cadherin is a mechanoresponsive adhesion receptor. Strikingly, the mechanical sensitivity response (gain) in terms of the measured cell-spread area as a function of imposed load (adhesive substrate rigidity) was consistently higher for N-cadherin-coated surfaces compared with ECM protein-coated surfaces. In addition, the cytoskeletal architecture of myocytes on an N-cadherin adhesive microenvironment was characteristically different from that on an ECM environment, suggesting that the two mechanotransductive cell adhesion systems may play both independent and complementary roles in myocyte cytoskeletal spatial organization. These results indicate that cell-to-cell-mediated force perception and transmission are involved in the organization and development of cardiac structure and function.",
"title": "Cardiac myocyte remodeling mediated by N-cadherin-dependent mechanosensing."
},
{
"docid": "29689140",
"text": "Dysregulated Wnt signaling is seen in approximately 30% of hepatocellular carcinomas; thus, finding pathways downstream of the activation of Wnt signaling is key. Here, using cre-lox technology, we deleted the Apc gene in the adult mouse liver and observed a rapid increase in nuclear beta-catenin and c-Myc, which is associated with an induction of proliferation that led to hepatomegaly within 4 days of gene deletion. To investigate the downstream pathways responsible for these phenotypes, we analyzed the impact of inactivating APC in the context of deficiency of the potentially key effectors beta-catenin and c-Myc. beta-catenin loss rescues both the proliferation and hepatomegaly phenotypes after APC loss. However, c-Myc deletion, which rescues the phenotypes of APC loss in the intestine, had no effect on the phenotypes of APC loss in the liver. The consequences of the deregulation of the Wnt pathway within the liver are therefore strikingly different from those observed within the intestine, with the vast majority of Wnt targets being beta-catenin-dependent but c-Myc-independent in the liver.",
"title": "B-catenin deficiency, but not Myc deletion, suppresses the immediate phenotypes of APC loss in the liver."
},
{
"docid": "20943272",
"text": "ADAM13 is a member of the disintegrin and metalloprotease protein family that is expressed on cranial neural crest cells surface and is essential for their migration. ADAM13 is an active protease that can cleave fibronectin in vitro and remodel a fibronectin substrate in vivo. Using a recombinant secreted protein containing both disintegrin and cysteine-rich domains of ADAM13, we show that this \"adhesive\" region of the protein binds directly to fibronectin. Fibronectin fusion proteins corresponding to the various functional domains were used to define the second heparin-binding domain as the ADAM13 binding site. Mutation of the syndecan-binding site (PPRR --> PPTM) within this domain abolishes binding of the recombinant disintegrin and cysteine-rich domains of ADAM13. We further show that the adhesive disintegrin and cysteine-rich domain of ADAM13 can promote cell adhesion via beta(1) integrins. This adhesion requires integrin activation and can be prevented by antibodies to the cysteine-rich domain of ADAM13 and beta(1) integrin. Finally, wild type, but not the E/A mutant of ADAM13 metalloprotease domain, can be shed from the cell surface, releasing the metalloprotease domain associated with the disintegrin and cysteine-rich domains. This suggests that ADAM13 shedding may involve its own metalloprotease activity and that the released protease may interact with both integrins and extracellular matrix proteins.",
"title": "ADAM13 disintegrin and cysteine-rich domains bind to the second heparin-binding domain of fibronectin."
},
{
"docid": "32797183",
"text": "Lineage analysis studies in the avian embryo have identified two types of smooth muscle cells (SMCs) in the tunica media of large elastic arteries; one that originates within the cardiac neural crest and is ectoderm in origin (Ect) and another that arises from local mesenchyme of mesodermal origin (Mes). To determine if differences in primary embryonic lineage can give rise to SMCs with stable differences in growth and differentiation properties, we isolated Ect and Mes SMCs from the Day 14 chick embryo aorta. We report that despite different primary embryonic origins, Ect and Mes SMCs express nearly identical levels of seven SMC differentiation markers in vitro, consistent with their common smooth muscle developmental fates in vivo. By contrast, Ect SMCs displayed a greater capacity for growth in serum-free medium than Mes SMCs, but only under conditions permitting short-range cell-cell interactions. Most of the peptide growth factors tested that might account for serum-independent growth (PDGF-AA, PDGF-BB, basic FGF, EGF, or activin) stimulated DNA synthesis to similar extents in Ect and Mes SMCs. However, we found dramatic, lineage-dependent differences in SMC responses to transforming growth factor-beta (TGF-beta). Exposure to TGF-beta 1 (0.4 to 400 pmole/liter) consistently increased DNA synthesis in Ect SMCs, whereas in paired cultures of Mes SMCs, TGF-beta 1 was growth inhibitory. In SMC cultures transfected with p3TP-lux, a luciferase reporter controlled by the TGF-beta 1-response elements of the human PAI-1 promoter, TGF-beta 1 (120 pM) produced 12 +/- 2-fold increases in luciferase activity in Ect SMCs and only 3 +/- 1.5-fold increases in Mes SMCs. Analysis of TGF-beta receptor phenotypes by Northern blot, radioligand binding, and crosslinking assays showed that Ect and Mes SMCs expressed similar levels of types I, II, and III TGF-beta receptors. However, using a polyclonal antibody specific for the chick type II TGF-beta receptor subunit, we demonstrate that Mes SMCs produce a fully glycosylated form of this protein while Ect SMCs elaborate only an unglycosylated type II TGF-beta receptor. These results show that Ect and Mes SMCs exhibit lineage-dependent differences in growth and receptor-mediated transcriptional responses to at least one important class of SMC morphogens and growth modifiers, e.g., the TGF-betas. Our findings suggest that different SMC populations within a common vessel wall may respond in lineage-dependent ways to signals that direct formation of the tunica media in the embryo and to factors involved in the progression of vascular disease later in life.",
"title": "Smooth muscle lineage diversity in the chick embryo. Two types of aortic smooth muscle cell differ in growth and receptor-mediated transcriptional responses to transforming growth factor-beta."
},
{
"docid": "31311495",
"text": "We have previously demonstrated that, following acquisition of endocrine resistance, breast cancer cells display an altered growth rate together with increased aggressive behaviour in vitro. Since dysfunctional cell-cell adhesive interactions can promote an aggressive phenotype, we investigated the integrity of this protein complex in our breast cancer model of tamoxifen resistance. In culture, tamoxifen-resistant MCF7 (TamR) cells grew as loosely packed colonies with loss of cell-cell junctions and demonstrated altered morphology characteristic of cells undergoing epithelial-to-mesenchymal transition (EMT). Neutralising E-cadherin function promoted the invasion and inhibited the aggregation of endocrine-sensitive MCF7 cells, whilst having little effect on the behaviour of TamR cells. Additionally, TamR cells had increased levels of tyrosine-phosphorylated beta-catenin, whilst serine/threonine-phosphorylated beta-catenin was decreased. These cells also displayed loss of association between beta-catenin and E-cadherin, increased cytoplasmic and nuclear beta-catenin and elevated transcription of beta-catenin target genes known to be involved in tumour progression and EMT. Inhibition of EGFR kinase activity in TamR cells reduced beta-catenin tyrosine phosphorylation, increased beta-catenin-E-cadherin association and promoted cell-cell adhesion. In such treated cells, the association of beta-catenin with Lef-1 and the transcription of c-myc, cyclin-D1, CD44 and COX-2 were also reduced. These results suggest that homotypic adhesion in tamoxifen-resistant breast cancer cells is dysfunctional due to EGFR-driven modulation of the phosphorylation status of beta-catenin and may contribute to an enhanced aggressive phenotype and transition towards a mesenchymal phenotype in vitro.",
"title": "Tamoxifen resistance in MCF7 cells promotes EMT-like behaviour and involves modulation of beta-catenin phosphorylation."
},
{
"docid": "24998764",
"text": "Chronic kidney disease is accompanied by increased large-artery stiffness, but the relation between glomerular filtration rate within the reference range and central or peripheral arterial stiffness has been understudied. The link between renal function and arterial stiffness was assessed in 305 patients with never-treated essential hypertension (men: 58%; age: 48+/-11 years, blood pressure: 151/95+/-20/11 mm Hg), free from overt cardiovascular disease and with serum creatinine values <1.4 mg/dL (men) and <1.2 mg/dL (women), who underwent noninvasive aortic and upper-limb pulse wave velocity (PWV) determination. Aortic PWV was strongly related to age (r=0.55; P<0.001), whereas upper-limb PWV had a weaker nonlinear relation with age (beta=1.392; P<0.001 for age; beta=-1.312; P<0.001 for age squared) and a weak relation with aortic PWV (r=0.22; P<0.001). Glomerular filtration rate (GFR), estimated according to the Mayo clinic equation for healthy subjects, was inversely correlated with large-artery stiffness, as assessed by aortic PWV (r=-0.34; P<0.001), and with peripheral artery stiffness, as assessed by upper-limb PWV (r=-0.25; P<0.001). In a multivariate linear regression, aortic PWV was independently predicted by age (beta=0.48; P<0.001), mean arterial pressure (beta=0.14; P=0.013), and GFR (beta=-0.13, P=0.029). Upper-limb PWV was predicted by GFR (beta=-0.24; P<0.001) and mean arterial pressure (beta=0.20; P<0.001). We conclude that, in hypertensive patients with normal renal function, an inverse relationship exists between GFR and stiffness of both central elastic and peripheral muscular arteries. These relations are in part independent from the effect of several confounders, including age, sex, and blood pressure values.",
"title": "Relation between renal function within the normal range and central and peripheral arterial stiffness in hypertension."
},
{
"docid": "20313748",
"text": "Adherens junctions (AJs), which are organized by adhesion proteins and the underlying actin cytoskeleton, probably sense pulling forces from adjacent cells and modulate opposing forces to maintain tissue integrity, but the regulatory mechanism remains unknown at the molecular level. Although the possibility that α-catenin acts as a direct linker between the membrane and the actin cytoskeleton for AJ formation and function has been minimized, here we show that α-catenin recruits vinculin, another main actin-binding protein of AJs, through force-dependent changes in α-catenin conformation. We identified regions in the α-catenin molecule that are required for its force-dependent binding of vinculin by introducing mutant α-catenin into cells and using in vitro binding assays. Fluorescence recovery after photobleaching analysis for α-catenin mobility and the existence of an antibody recognizing α-catenin in a force-dependent manner further supported the notion that α-catenin is a tension transducer that translates mechanical stimuli into a chemical response, resulting in AJ development.",
"title": "α-Catenin as a tension transducer that induces adherens junction development"
},
{
"docid": "8219248",
"text": "A set of 57 synthetic peptides encompassing the entire triplehelical domain of human collagen III was used to locate binding sites for the collagen-binding integrin alpha(2)beta(1). The capacity of the peptides to support Mg(2+)-dependent binding of several integrin preparations was examined. Wild-type integrins (recombinant alpha(2) I-domain, alpha(2)beta(1) purified from platelet membranes, and recombinant soluble alpha(2)beta(1) expressed as an alpha(2)-Fos/beta(1)-Jun heterodimer) bound well to only three peptides, two containing GXX'GER motifs (GROGER and GMOGER, where O is hydroxyproline) and one containing two adjacent GXX'GEN motifs (GLKGEN and GLOGEN). Two mutant alpha(2) I-domains were tested: the inactive T221A mutant, which recognized no peptides, and the constitutively active E318W mutant, which bound a larger subset of peptides. Adhesion of activated human platelets to GER-containing peptides was greater than that of resting platelets, and HT1080 cells bound well to more of the peptides compared with platelets. Binding of cells and recombinant proteins was abolished by anti-alpha(2) monoclonal antibody 6F1 and by chelation of Mg(2+). We describe two novel high affinity integrin-binding motifs in human collagen III (GROGER and GLOGEN) and a third motif (GLKGEN) that displays intermediate activity. Each motif was verified using shorter synthetic peptides.",
"title": "Use of synthetic peptides to locate novel integrin alpha2beta1-binding motifs in human collagen III."
},
{
"docid": "19855358",
"text": "Direct reprogramming strategies enable rapid conversion of somatic cells to cardiomyocytes or cardiomyocyte-like cells without going through the pluripotent state. A recently described protocol couples Yamanaka factor induction with pluripotency inhibition followed by BMP4 treatment to achieve rapid reprogramming of mouse fibroblasts to beating cardiomyocyte-like cells. The original study was performed using Matrigel-coated tissue culture polystyrene (TCPS), a stiff material that also non-specifically adsorbs serum proteins. Protein adsorption-resistant poly(ethylene glycol) (PEG) materials can be covalently modified to present precise concentrations of adhesion proteins or peptides without the unintended effects of non-specifically adsorbed proteins. Here, we describe an improved protocol that incorporates custom-engineered materials. We first reproduced the Efe et al. protocol on Matrigel-coated TCPS (the original material), reprogramming adult mouse tail-tip mouse fibroblasts (TTF) and mouse embryonic fibroblasts (MEF) to cardiomyocyte-like cells that demonstrated striated sarcomeric α-actinin staining, spontaneous calcium transients, and visible beating. We then designed poly(ethylene glycol) culture substrates to promote MEF adhesion via laminin and RGD-binding integrins. PEG hydrogels improved proliferation and reprogramming efficiency (evidenced by beating patch number and area, gene expression, and flow cytometry), yielding almost twice the number of sarcomeric α-actinin positive cardiomyocyte-like cells as the originally described substrate. These results illustrate that cellular reprogramming may be enhanced using custom-engineered materials.",
"title": "Direct reprogramming of mouse fibroblasts to cardiomyocyte-like cells using Yamanaka factors on engineered poly(ethylene glycol) (PEG) hydrogels."
},
{
"docid": "2682997",
"text": "Despite the importance of CNS blood vessels, the molecular mechanisms that regulate CNS angiogenesis and blood-brain barrier (BBB) formation are largely unknown. Here we analyze the role of Wnt/beta-catenin signaling in regulating the formation of CNS blood vessels. First, through the analysis of TOP-Gal Wnt reporter mice, we identify that canonical Wnt/beta-catenin signaling is specifically activated in CNS, but not non-CNS, blood vessels during development. This activation correlates with the expression of different Wnt ligands by neural progenitor cells in distinct locations throughout the CNS, including Wnt7a and Wnt7b in ventral regions and Wnt1, Wnt3, Wnt3a, and Wnt4 in dorsal regions. Blockade of Wnt/beta-catenin signaling in vivo specifically disrupts CNS, but not non-CNS, angiogenesis. These defects include reduction in vessel number, loss of capillary beds, and the formation of hemorrhagic vascular malformations that remain adherent to the meninges. Furthermore, we demonstrate that Wnt/beta-catenin signaling regulates the expression of the BBB-specific glucose transporter glut-1. Taken together these experiments reveal an essential role for Wnt/beta-catenin signaling in driving CNS-specific angiogenesis and provide molecular evidence that angiogenesis and BBB formation are in part linked.",
"title": "Wnt/beta-catenin signaling is required for CNS, but not non-CNS, angiogenesis."
},
{
"docid": "23160444",
"text": "Neuronal growth cones move forward by dynamically connecting actin-based motility to substrate adhesion, but the mechanisms at the individual molecular level remain unclear. We cultured primary neurons on N-cadherin-coated micropatterned substrates, and imaged adhesion and cytoskeletal proteins at the ventral surface of growth cones using single particle tracking combined to photoactivated localization microscopy (sptPALM). We demonstrate transient interactions in the second time scale between flowing actin filaments and immobilized N-cadherin/catenin complexes, translating into a local reduction of the actin retrograde flow. Normal actin flow on micropatterns was rescued by expression of a dominant negative N-cadherin construct competing for the coupling between actin and endogenous N-cadherin. Fluorescence recovery after photobleaching (FRAP) experiments confirmed the differential kinetics of actin and N-cadherin, and further revealed a 20% actin population confined at N-cadherin micropatterns, contributing to local actin accumulation. Computer simulations with relevant kinetic parameters modeled N-cadherin and actin turnover well, validating this mechanism. Such a combination of short- and long-lived interactions between the motile actin network and spatially restricted adhesive complexes represents a two-tiered clutch mechanism likely to sustain dynamic environment sensing and provide the force necessary for growth cone migration.",
"title": "Two-tiered coupling between flowing actin and immobilized N-cadherin/catenin complexes in neuronal growth cones."
},
{
"docid": "30884033",
"text": "Deciphering the molecular basis of stem cell pluripotency is fundamental to the understanding of stem cell biology, early embryonic development, and to the clinical application of regenerative medicine. We report here that the molecular chaperone heat shock protein 90 (Hsp90) is essential for mouse embryonic stem cell (ESC) pluripotency through regulating multiple pluripotency factors, including Oct4, Nanog, and signal transducer and activator of transcription 3. Inhibition of Hsp90 by either 17-N-Allylamino-17-demethoxygeldanamycin or miRNA led to ESC differentiation. Overexpression of Hsp90β partially rescued the phenotype; in particular, the levels of Oct4 and Nanog were restored. Notably, Hsp90 associated with Oct4 and Nanog in the same cellular complex and protected them from degradation by the ubiquitin proteasome pathway, suggesting that Oct4 and Nanog are potential novel Hsp90 client proteins. In addition, Hsp90 inhibition reduced the mRNA level of Oct4, but not that of Nanog, indicating that Hsp90 participates in Oct4 mRNA processing or maturation. Hsp90 inhibition also increased expression of some protein markers for mesodermal lineages, implying that Hsp90 suppresses mesodermal differentiation from ESCs. These findings support a new role for Hsp90 in maintaining ESC pluripotency by sustaining the level of multiple pluripotency factors, particularly Oct4 and Nanog.",
"title": "Regulation of embryonic stem cell pluripotency by heat shock protein 90."
},
{
"docid": "5321708",
"text": "Cytokinesis is the final stage in cell division. Although integrins can regulate cytokinesis, the mechanisms involved are not fully understood. In this study, we demonstrate that integrin-regulated ERK (extracellular signal-related kinase) and RSK (p90 ribosomal S6 kinase) signaling promotes successful cytokinesis. Inhibiting the activation of ERK and RSK in CHO cells by a mutation in the integrin β1 cytoplasmic tail or with pharmacological inhibitors results in the accumulation of cells with midbodies and the formation of binucleated cells. Activation of ERK and RSK signaling by the expression of constitutively active RAF1 suppresses the mutant phenotype in a RSK-dependent manner. Constitutively active RSK2 also restores cytokinesis inhibited by the mutant integrin. Importantly, the regulatory role of the RSK pathway is not specific to CHO cells. MCF-10A human mammary epithelial cells and HPNE human pancreatic ductal epithelial cells exhibit a similar dependence on RSK for successful cytokinesis. In addition, depriving mitotic MCF10A cells of integrin-mediated adhesion by incubating them in suspension suppressed ERK and RSK activation and resulted in a failure of cytokinesis. Furthermore, inhibition of RSK or integrins within the 3D context of a developing salivary gland organ explant also leads to an accumulation of epithelial cells with midbodies, suggesting a similar defect in cytokinesis. Interestingly, neither ERK nor RSK regulates cytokinesis in human fibroblasts, suggesting cell-type specificity. Taken together, our results identify the integrin-RSK signaling axis as an important regulator of cytokinesis in epithelial cells. We propose that the proper interaction of cells with their microenvironment through integrins contributes to the maintenance of genomic stability by promoting the successful completion of cytokinesis.",
"title": "Integrins promote cytokinesis through the RSK signaling axis."
},
{
"docid": "21164071",
"text": "Integrins are membrane receptors which mediate cell-cell or cell-matrix adhesion. Integrin alpha IIb beta 3 (glycoprotein IIb-IIIa) acts as a fibrinogen receptor of platelets and mediates platelet aggregation. Platelet activation is required for alpha IIb beta 3 to shift from noncompetent to competent for binding soluble fibrinogen. The steps involved in this transition are poorly understood. We have studied a variant of Glanzmann thrombasthenia, a congenital bleeding disorder characterized by absence of platelet aggregation and fibrinogen binding. The patient's platelets did not bind fibrinogen after platelet activation by ADP or thrombin, though his platelets contained alpha IIb beta 3. However, isolated alpha IIb beta 3 was able to bind to an Arg-Gly-Asp-Ser affinity column, and binding of soluble fibrinogen to the patient's platelets could be triggered by modulators of alpha IIb beta 3 conformation such as the Arg-Gly-Asp-Ser peptide and alpha-chymotrypsin. These data suggested that a functional Arg-Gly-Asp binding site was present within alpha IIb beta 3 and that the patient's defect was not secondary to a blockade of alpha IIb beta 3 in a noncompetent conformational state. This was evocative of a defect in the coupling between platelet activation and alpha IIb beta 3 up-regulation. We therefore sequenced the cytoplasmic domain of beta 3, following polymerase chain reaction (PCR) on platelet RNA, and found a T-->C mutation at nucleotide 2259, corresponding to a Ser-752-->Pro substitution. This mutation is likely to be responsible for the uncoupling of alpha IIb beta 3 from cellular activation because (i) it is not a polymorphism, (ii) it is the only mutation in the entire alpha IIb beta 3 sequence, and (iii) genetic analysis of the family showed that absence of the Pro-752 beta 3 allele was associated with the normal phenotype. Our data thus identify the C-terminal portion of the cytoplasmic domain of beta 3 as an intrinsic element in the coupling between alpha IIb beta 3 and platelet activation.",
"title": "Ser-752-->Pro mutation in the cytoplasmic domain of integrin beta 3 subunit and defective activation of platelet integrin alpha IIb beta 3 (glycoprotein IIb-IIIa) in a variant of Glanzmann thrombasthenia."
},
{
"docid": "8677721",
"text": "The N-myc downstream regulated gene 1 (NDRG1) is significantly associated with advanced tumor stages and poor survival of hepatocellular carcinoma (HCC), thereby implicating it as a potential target for HCC treatment. We aim to further understand its biological roles in hepatocarcinogenesis, as a means to exploit it for therapeutic purposes. By screening using the ProtoArray® Human Protein Microarrays, we identified glycogen synthase kinase 3β (GSK-3β) and the orphan nuclear receptor (Nur77) as potential interaction partners of NDRG1. These interactions were confirmed in HCC cell lines in vitro by co-immunoprecipitation; and co-localizations of NDRG1 with GSK-3β and Nur77 were observed by immunofluorescence staining. Additionally, high levels of NDRG1 competitively bind to GSK-3β and Nur77 to allow β-catenin to escape degradation, with consequent elevated levels of downstream oncogenic genes. In vivo, we consistently observed that NDRG1 suppression in HCC xenografts decreased β-catenin levels and its downstream target Cyclin D1, with concomitant tumor growth inhibition. Clinically, the over-expression of NDRG1 in HCC patient samples is positively correlated with GSK-3β-9ser (| R | = 0.28, p = 0.01), Nur77 (| R | = 0.42, p < 0.001), and β-catenin (| R |= 0.32, p = 0.003) expressions. In conclusion, we identified GSK-3β and Nur77 as novel interaction partners of NDRG1. These protein-protein interactions regulate the turnover of β-catenin and subsequent downstream signaling mediated by β-catenin in HCC cells, and provides potential targets for future therapeutic interventions.",
"title": "NDRG1 promotes growth of hepatocellular carcinoma cells by directly interacting with GSK-3β and Nur77 to prevent β-catenin degradation"
},
{
"docid": "21562657",
"text": "K3/MIR1 and K5/MIR2 of Kaposi's sarcoma-associated herpesvirus (KSHV) are viral members of the membrane-associated RING-CH (MARCH) ubiquitin ligase family and contribute to viral immune evasion by directing the conjugation of ubiquitin to immunostimulatory transmembrane proteins. In a quantitative proteomic screen for novel host cell proteins downregulated by viral immunomodulators, we previously observed that K5, as well as the human immunodeficiency virus type 1 (HIV-1) immunomodulator VPU, reduced steady-state levels of bone marrow stromal cell antigen 2 (BST2; also called CD317 or tetherin), suggesting that BST2 might be a novel substrate of K5 and VPU. Recent work revealed that in the absence of VPU, HIV-1 virions are tethered to the plasma membrane in BST2-expressing HeLa cells. By targeting BST2, K5 might thus similarly overcome an innate antiviral host defense mechanism. Here we establish that despite its type II transmembrane topology and carboxy-terminal glycosylphosphatidylinositol (GPI) anchor, BST2 represents a bona fide target of K5 that is downregulated during primary infection by and reactivation of KSHV. Upon exit of the protein from the endoplasmic reticulum, lysines in the short amino-terminal domain of BST2 are ubiquitinated by K5, resulting in rapid degradation of BST2. Ubiquitination of BST2 is required for degradation, since BST2 lacking cytosolic lysines was K5 resistant and ubiquitin depletion by proteasome inhibitors restored BST2 surface expression. Thus, BST2 represents the first type II transmembrane protein targeted by K5 and the first example of a protein that is both ubiquitinated and GPI linked. We further demonstrate that KSHV release is decreased in the absence of K5 in a BST2-dependent manner, suggesting that K5 contributes to the evasion of intracellular antiviral defense programs.",
"title": "Molecular mechanism of BST2/tetherin downregulation by K5/MIR2 of Kaposi's sarcoma-associated herpesvirus."
},
{
"docid": "25858295",
"text": "The murine homeo box gene Nkx2-5 is expressed in precardiac mesoderm and in the myocardium of embryonic and fetal hearts. Targeted interruption of Nkx2-5 resulted in abnormal heart morphogenesis, growth retardation and embryonic lethality at approximately 9-10 days postcoitum (p.c.). Heart tube formation occurred normally in mutant embryos, but looping morphogenesis, a critical determinant of heart form, was not initiated at the linear heart tube stage (8.25-8.5 days p.c.). Commitment to the cardiac muscle lineage, expression of most myofilament genes and myofibrillogenesis were not compromised. However, the myosin light-chain 2V gene (MLC2V) was not expressed in mutant hearts nor in mutant ES cell-derived cardiocytes. MLC2V expression normally occurs only in ventricular cells and is the earliest known molecular marker of ventricular differentiation. The regional expression in mutant hearts of two other ventricular markers, myosin heavy-chain beta and cyclin D2, indicated that not all ventricle-specific gene expression is dependent on Nkx2-5. The data demonstrate that Nkx2-5 is essential for normal heart morphogenesis, myogenesis, and function. Furthermore, this gene is a component of a genetic pathway required for myogenic specialization of the ventricles.",
"title": "Myogenic and morphogenetic defects in the heart tubes of murine embryos lacking the homeo box gene Nkx2-5."
},
{
"docid": "52887689",
"text": "In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.",
"title": "Guidelines for the use and interpretation of assays for monitoring autophagy."
},
{
"docid": "6422576",
"text": "A growing number of cellular regulatory mechanisms are being linked to protein modification by the polypeptide ubiquitin. These include key transitions in the cell cycle, class I antigen processing, signal transduction pathways, and receptor-mediated endocytosis. In most, but not all, of these examples, ubiquitination of a protein leads to its degradation by the 26S proteasome. Following attachment of ubiquitin to a substrate and binding of the ubiquitinated protein to the proteasome, the bound substrate must be unfolded (and eventually deubiquitinated) and translocated through a narrow set of channels that leads to the proteasome interior, where the polypeptide is cleaved into short peptides. Protein ubiquitination and deubiquitination are both mediated by large enzyme families, and the proteasome itself comprises a family of related but functionally distinct particles. This diversity underlies both the high substrate specificity of the ubiquitin system and the variety of regulatory mechanisms that it serves.",
"title": "Ubiquitin-dependent protein degradation."
},
{
"docid": "10991183",
"text": "How individual cells respond to mechanical forces is of considerable interest to biologists as force affects many aspects of cell behaviour. The application of force on integrins triggers cytoskeletal rearrangements and growth of the associated adhesion complex, resulting in increased cellular stiffness, also known as reinforcement. Although RhoA has been shown to play a role during reinforcement, the molecular mechanisms that regulate its activity are unknown. By combining biochemical and biophysical approaches, we identified two guanine nucleotide exchange factors (GEFs), LARG and GEF-H1, as key molecules that regulate the cellular adaptation to force. We show that stimulation of integrins with tensional force triggers activation of these two GEFs and their recruitment to adhesion complexes. Surprisingly, activation of LARG and GEF-H1 involves distinct signalling pathways. Our results reveal that LARG is activated by the Src family tyrosine kinase Fyn, whereas GEF-H1 catalytic activity is enhanced by ERK downstream of a signalling cascade that includes FAK and Ras.",
"title": "The Rho GEFs LARG and GEF-H1 regulate the mechanical response to force on integrins"
},
{
"docid": "13714201",
"text": "Aims The gut microbiome influences metabolic syndrome (MetS) and inflammation and is therapeutically modifiable. Arterial stiffness is poorly correlated with most traditional risk factors. Our aim was to examine whether gut microbial composition is associated with arterial stiffness. Methods and results We assessed the correlation between carotid-femoral pulse wave velocity (PWV), a measure of arterial stiffness, and gut microbiome composition in 617 middle-aged women from the TwinsUK cohort with concurrent serum metabolomics data. Pulse wave velocity was negatively correlated with gut microbiome alpha diversity (Shannon index, Beta(SE)= -0.25(0.07), P = 1 × 10-4) after adjustment for covariates. We identified seven operational taxonomic units associated with PWV after adjusting for covariates and multiple testing-two belonging to the Ruminococcaceae family. Associations between microbe abundances, microbe diversity, and PWV remained significant after adjustment for levels of gut-derived metabolites (indolepropionate, trimethylamine oxide, and phenylacetylglutamine). We linearly combined the PWV-associated gut microbiome-derived variables and found that microbiome factors explained 8.3% (95% confidence interval 4.3-12.4%) of the variance in PWV. A formal mediation analysis revealed that only a small proportion (5.51%) of the total effect of the gut microbiome on PWV was mediated by insulin resistance and visceral fat, c-reactive protein, and cardiovascular risk factors after adjusting for age, body mass index, and mean arterial pressure. Conclusions Gut microbiome diversity is inversely associated with arterial stiffness in women. The effect of gut microbiome composition on PWV is only minimally mediated by MetS. This first human observation linking the gut microbiome to arterial stiffness suggests that targeting the microbiome may be a way to treat arterial ageing.",
"title": "Gut microbial diversity is associated with lower arterial stiffness in women"
},
{
"docid": "11831598",
"text": "Bistability in developmental pathways refers to the generation of binary outputs from graded or noisy inputs. Signaling thresholds are critical for bistability. Specification of the left/right (LR) axis in vertebrate embryos involves bistable expression of transforming growth factor beta (TGFbeta) member NODAL in the left lateral plate mesoderm (LPM) controlled by feed-forward and feedback loops. Here we provide evidence that bone morphogenetic protein (BMP)/SMAD1 signaling sets a repressive threshold in the LPM essential for the integrity of LR signaling. Conditional deletion of Smad1 in the LPM led to precocious and bilateral pathway activation. NODAL expression from both the left and right sides of the node contributed to bilateral activation, indicating sensitivity of mutant LPM to noisy input from the LR system. In vitro, BMP signaling inhibited NODAL pathway activation and formation of its downstream SMAD2/4-FOXH1 transcriptional complex. Activity was restored by overexpression of SMAD4 and in embryos, elevated SMAD4 in the right LPM robustly activated LR gene expression, an effect reversed by superactivated BMP signaling. We conclude that BMP/SMAD1 signaling sets a bilateral, repressive threshold for NODAL-dependent Nodal activation in LPM, limiting availability of SMAD4. This repressive threshold is essential for bistable output of the LR system.",
"title": "BMP/SMAD1 signaling sets a threshold for the left/right pathway in lateral plate mesoderm and limits availability of SMAD4."
},
{
"docid": "17648235",
"text": "De-regulation of the wingless and integration site growth factor (WNT) signaling pathway via mutations in APC and Axin, proteins that target β-catenin for destruction, have been linked to various types of human cancer. These genetic alterations rarely, if ever, are observed in breast tumors. However, various lines of evidence suggest that WNT signaling may also be de-regulated in breast cancer. Most breast tumors show hypermethylation of the promoter region of secreted Frizzled-related protein 1 (sFRP1), a negative WNT pathway regulator, leading to downregulation of its expression. As a consequence, WNT signaling is enhanced and may contribute to proliferation of human breast tumor cells. We previously demonstrated that, in addition to the canonical WNT/β-catenin pathway, WNT signaling activates the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway in mouse mammary epithelial cells via epidermal growth factor receptor (EGFR) transactivation. Using the WNT modulator sFRP1 and short interfering RNA-mediated Dishevelled (DVL) knockdown, we interfered with autocrine WNT signaling at the ligand-receptor level. The impact on proliferation was measured by cell counting, YOPRO, and the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) assay; β-catenin, EGFR, ERK1/2 activation, and PARP (poly [ADP-ribose]polymerase) cleavages were assessed by Western blotting after treatment of human breast cancer cell lines with conditioned media, purified proteins, small-molecule inhibitors, or blocking antibodies. Phospho-DVL and stabilized β-catenin are present in many breast tumor cell lines, indicating autocrine WNT signaling activity. Interfering with this loop decreases active β-catenin levels, lowers ERK1/2 activity, blocks proliferation, and induces apoptosis in MDA-MB-231, BT474, SkBr3, JIMT-1, and MCF-7 cells. The effects of WNT signaling are mediated partly by EGFR transactivation in human breast cancer cells in a metalloprotease- and Src-dependent manner. Furthermore, Wnt1 rescues estrogen receptor-positive (ER+) breast cancer cells from the anti-proliferative effects of 4-hydroxytamoxifen (4-HT) and this activity can be blocked by an EGFR tyrosine kinase inhibitor. Our data show that interference with autocrine WNT signaling in human breast cancer reduces proliferation and survival of human breast cancer cells and rescues ER+ tumor cells from 4-HT by activation of the canonical WNT pathway and EGFR transactivation. These findings suggest that interference with WNT signaling at the ligand-receptor level in combination with other targeted therapies may improve the efficiency of breast cancer treatments.",
"title": "Autocrine WNT signaling contributes to breast cancer cell proliferation via the canonical WNT pathway and EGFR transactivation"
},
{
"docid": "14149065",
"text": "E-cadherin has been linked to the suppression of tumor growth and the inhibition of cell proliferation in culture. We observed that progressively decreasing the seeding density of normal rat kidney-52E (NRK-52E) or MCF-10A epithelial cells from confluence, indeed, released cells from growth arrest. Unexpectedly, a further decrease in seeding density so that cells were isolated from neighboring cells decreased proliferation. Experiments using microengineered substrates showed that E-cadherin engagement stimulated the peak in proliferation at intermediate seeding densities, and that the proliferation arrest at high densities did not involve E-cadherin, but rather resulted from a crowding-dependent decrease in cell spreading against the underlying substrate. Rac1 activity, which was induced by E-cadherin engagement specifically at intermediate seeding densities, was required for the cadherin-stimulated proliferation, and the control of Rac1 activation by E-cadherin was mediated by p120-catenin. Together, these findings demonstrate a stimulatory role for E-cadherin in proliferative regulation, and identify a simple mechanism by which cell–cell contact may trigger or inhibit epithelial cell proliferation in different settings.",
"title": "E-cadherin engagement stimulates proliferation via Rac1"
},
{
"docid": "8453819",
"text": "The integrin family of heterodimeric cell-surface receptors are fundamental in cell-cell and cell-matrix adhesion. Changes to either integrin-ligand affinity or integrin gene expression are central to a variety of disease processes, including inflammation, cardiovascular disease and cancer. In screening for novel activators of integrin-ligand affinity we identified the previously uncharacterised multi-transmembrane domain protein Fam38A, located at the endoplasmic reticulum (ER). siRNA knockdown of Fam38A in epithelial cells inactivates endogenous beta1 integrin, reducing cell adhesion. Fam38A mediates integrin activation by recruiting the small GTPase R-Ras to the ER, which activates the calcium-activated protease calpain by increasing Ca(2+) release from cytoplasmic stores. Fam38A-induced integrin activation is blocked by inhibition of either R-Ras or calpain activity, or by siRNA knockdown of talin, a well-described calpain substrate. This highlights a novel mechanism for integrin activation by Fam38A, utilising calpain and R-Ras signalling from the ER. These data represent the first description of a novel spatial regulator of R-Ras, of an alternative integrin activation-suppression pathway based on direct relocalisation of R-Ras to the ER, and of a mechanism linking R-Ras and calpain signalling from the ER with modulation of integrin-ligand affinity.",
"title": "Integrin activation by Fam38A uses a novel mechanism of R-Ras targeting to the endoplasmic reticulum."
},
{
"docid": "5633876",
"text": "BMP is thought to induce hESC differentiation toward multiple lineages including mesoderm and trophoblast. The BMP-induced trophoblast phenotype is a long-standing paradox in stem cell biology. Here we readdressed BMP function in hESCs and mouse epiblast-derived cells. We found that BMP4 cooperates with FGF2 (via ERK) to induce mesoderm and to inhibit endoderm differentiation. These conditions induced cells with high levels of BRACHYURY (BRA) that coexpressed CDX2. BRA was necessary for and preceded CDX2 expression; both genes were essential for expression not only of mesodermal genes but also of trophoblast-associated genes. Maximal expression of the latter was seen in the absence of FGF but these cells coexpressed mesodermal genes and moreover they differed in cell surface and epigenetic properties from placental trophoblast. We conclude that BMP induces human and mouse pluripotent stem cells primarily to form mesoderm, rather than trophoblast, acting through BRA and CDX2.",
"title": "BRACHYURY and CDX2 Mediate BMP-Induced Differentiation of Human and Mouse Pluripotent Stem Cells into Embryonic and Extraembryonic Lineages"
}
] |
PLAIN-614
|
Asia
|
[
{
"docid": "MED-1320",
"text": "Context Because of a different degree of processing and nutrient contents, brown rice and white rice may have different effects on risk of type 2 diabetes. Objective To prospectively examine white rice and brown rice consumptions in relation to type 2 diabetes risk in US men and women aged 26–87 yr. Design and Setting The Health Professionals Follow-up Study (1986–2006) and the Nurses’ Health Study I (1984–2006) and II (1991–2005). Participants We prospectively ascertained diet, lifestyle practices, and disease status among 39,765 men and 157,463 women in these cohorts. All participants were free of diabetes, cardiovascular disease, and cancer at baseline. Intake of white rice, brown rice, other foods, and nutrients was assessed at baseline and updated every 2–4 years. Results During 3,318,196 person-years of follow-up, we documented 10,507 incident cases of type 2 diabetes. After multivariate adjustment for age and other lifestyle and dietary risk factors, higher intake of white rice was associated with a higher risk of type 2 diabetes. The pooled relative risk (95% confidence interval) of type 2 diabetes comparing ≥5 servings/week with <1 serving/month of white rice was 1.17 (1.02, 1.36). In contrast, high brown rice intake was associated with a lower risk of type 2 diabetes: The pooled multivariate relative risk (95% confidence interval) was 0.89 (0.81, 0.97) for ≥ 2 servings/week of brown rice as compared with <1 serving/month. We estimated that replacing 50 grams/day (cooked, equivalent to ⅓ serving/day) intake of white rice with the same amount of brown rice was associated with a 16% (95% confidence interval: 9%, 21%) lower risk of type 2 diabetes, whereas the same replacement with whole grains as a group was associated with a 36% (95% confidence interval: 30%, 42%) lower diabetes risk. Conclusions Substitution of whole grains, including brown rice, for white rice may lower risk of type 2 diabetes. These data support the recommendation that most carbohydrate intake should come from whole grains rather than refined grains to facilitate the prevention of type 2 diabetes.",
"title": "White Rice, Brown Rice, and Risk of Type 2 Diabetes in US Men and Women"
},
{
"docid": "MED-1530",
"text": "BACKGROUND: Prospective cohort studies have examined mortality and overall cancer incidence among vegetarians, but the results have been inconclusive. AIMS: The objective of the present meta-analysis was to investigate cardiovascular disease mortality and cancer incidence among vegetarians and nonvegetarians. METHODS: Medline, EMBASE and Web Of Science databases were searched for cohort studies published from inception to September 2011. Studies were included if they contained the relative risk (RR) and corresponding 95% CI. Participants were from the UK, Germany, California, USA, the Netherlands and Japan. RESULTS: Seven studies with a total of 124,706 participants were included in this analysis. All-cause mortality in vegetarians was 9% lower than in nonvegetarians (RR = 0.91; 95% CI, 0.66-1.16). The mortality from ischemic heart disease was significantly lower in vegetarians than in nonvegetarians (RR = 0.71; 95% CI, 0.56-0.87). We observed a 16% lower mortality from circulatory diseases (RR = 0.84; 95% CI, 0.54-1.14) and a 12% lower mortality from cerebrovascular disease (RR = 0.88; 95% CI, 0.70-1.06) in vegetarians compared with nonvegetarians. Vegetarians had a significantly lower cancer incidence than nonvegetarians (RR = 0.82; 95% CI, 0.67-0.97). CONCLUSIONS: Our results suggest that vegetarians have a significantly lower ischemic heart disease mortality (29%) and overall cancer incidence (18%) than nonvegetarians. Copyright © 2012 S. Karger AG, Basel.",
"title": "Cardiovascular disease mortality and cancer incidence in vegetarians: a meta-analysis and systematic review."
},
{
"docid": "MED-666",
"text": "Breast pain is a common condition affecting most women at some stage in their reproductive life. Mastalgia is resistant to treatment in 6% of cyclical and 26% non-cyclical patients. Surgery is not widely used to treat this condition and only considered in patients with severe mastalgia resistant to medication. The aims of this study were to audit the efficacy of surgery in severe treatment resistant mastalgia and to assess patient satisfaction following surgery. This is a retrospective review of the medical records of all patients seen in mastalgia clinic in the University Hospital of Wales, Cardiff since 1973. A postal questionnaire was distributed to all patients who had undergone surgery. Results showed that of the 1054 patients seen in mastalgia clinic, 12 (1.2%) had undergone surgery. Surgery included 8 subcutaneous mastectomies with implants (3 bilateral, 5 unilateral), 1 bilateral simple mastectomy and 3 quadrantectomies (1 having a further simple mastectomy). The median duration of symptoms was 6.5 years (range 2-16 years). Five patients (50%) were pain free following surgery, 3 developed capsular contractures and 2 wound infections with dehiscence. Pain persisted in both patients undergoing quadrantectomy. We conclude that surgery for mastalgia should only be considered in a minority of patients. Patients should be informed of possible complications inherent of reconstructive surgery and warned that in 50% cases their pain will not be improved.",
"title": "Is there a role for surgery in the treatment of mastalgia?"
},
{
"docid": "MED-1322",
"text": "Several studies have suggested a protective effect of intake of whole grains, but not refined grains on type 2 diabetes risk, but the dose-response relationship between different types of grains and type 2 diabetes has not been established. We conducted a systematic review and meta-analysis of prospective studies of grain intake and type 2 diabetes. We searched the PubMed database for studies of grain intake and risk of type 2 diabetes, up to June 5th, 2013. Summary relative risks were calculated using a random effects model. Sixteen cohort studies were included in the analyses. The summary relative risk per 3 servings per day was 0.68 (95% CI 0.58-0.81, I(2) = 82%, n = 10) for whole grains and 0.95 (95% CI 0.88-1.04, I(2) = 53%, n = 6) for refined grains. A nonlinear association was observed for whole grains, p nonlinearity < 0.0001, but not for refined grains, p nonlinearity = 0.10. Inverse associations were observed for subtypes of whole grains including whole grain bread, whole grain cereals, wheat bran and brown rice, but these results were based on few studies, while white rice was associated with increased risk. Our meta-analysis suggests that a high whole grain intake, but not refined grains, is associated with reduced type 2 diabetes risk. However, a positive association with intake of white rice and inverse associations between several specific types of whole grains and type 2 diabetes warrant further investigations. Our results support public health recommendations to replace refined grains with whole grains and suggest that at least two servings of whole grains per day should be consumed to reduce type 2 diabetes risk.",
"title": "Whole grain and refined grain consumption and the risk of type 2 diabetes: a systematic review and dose-response meta-analysis of cohort studies."
},
{
"docid": "MED-3833",
"text": "Preclinical and correlative studies suggest reduced breast cancer with higher lignan intake or blood levels. We conducted a pilot study of modulation of risk biomarkers for breast cancer in premenopausal women after administration of the plant lignan secoisolariciresinol given as the diglycoside (SDG). Eligibility criteria included regular menstrual cycles, no oral contraceptives, a greater than 3-fold increase in 5 year risk, and baseline Ki-67 ≥2% in areas of hyperplasia in breast tissue sampled by random periareolar fine needle aspiration (RPFNA) during the follicular phase of the menstrual cycle. SDG 50 mg daily was given for 12 months, followed by repeat RPFNA. The primary endpoint was change in Ki-67. Secondary endpoints included change in cytomorphology, mammographic breast density, serum bioavailable estradiol, and testosterone IGF-I and IGFBP-3, and plasma lignan levels. Forty-five of 49 eligible women completed the study with excellent compliance (median = 96%) and few serious side effects (4% grade 3). Median plasma enterolactone increased ~ 9-fold, and total lignans 16 fold. Thirty-six (80%) of the 45 evaluable subjects demonstrated a decrease in Ki-67, from a median of 4% (range 2–16.8 %) to 2% (range 0–15.2%) (p<0.001 by Wilcoxon signed rank test). A decrease from baseline in the proportion of women with atypical cytology (p=0.035) was also observed. Based on favorable risk biomarker modulation and lack of adverse events, we are initiating a randomized trial of SDG vs. placebo in premenopausal women.",
"title": "Reduction in Ki-67 in Benign Breast Tissue of High Risk Women with the Lignan Secoisolariciresinol Diglycoside (SDG)"
},
{
"docid": "MED-3248",
"text": "OBJECTIVE: To examine the relation between retinal artery disease and cerebral small-vessel disease (SVD). METHODS: In a prospective cohort of patients with symptomatic atherosclerotic disease, the authors performed retinal photographs and brain MRI. Two ophthalmologists, not aware of the MR results, independently assessed retinal arterial narrowing, crossings, sclerosis, and tortuosity according to standard scoring lists. Two observers independently assessed white matter lesions (WML) and lacunar infarcts on the MR images. Lesions were considered abnormal only when both ophthalmologists or MR raters agreed. Cerebral SVD was defined as the presence of WML or lacunar infarcts. RESULTS: In 179 patients, retinal photographs and brain MRI were performed. Of the 108 patients with MR signs of SVD, 92% had at least one retinal vascular abnormality; of the 71 patients without SVD, 77% had retinal pathology (p < 0.01). All types of retinal vascular pathology occurred more frequently in patients with SVD, but only retinal arterial narrowing and sclerosis differed significantly. In the 109 normotensive patients, the presence of any retinal vascular change correlated with signs of SVD (p = 0.01). CONCLUSION: Pathologic changes in the retinal arteries parallel changes in the small cerebral arteries that cause WML and lacunes, both in hypertensive and in normotensive patients.",
"title": "Retinal arterial changes correlate with cerebral small-vessel disease."
},
{
"docid": "MED-3959",
"text": "Context: Earlier age at menarche is associated with rapid infancy weight gain and childhood obesity. The role of hormone levels in mediating these associations is unclear. Objective: The aim of this study was to identify childhood hormone levels at age 8 yr that are associated with early menarche, independent of body size. Design, Settings, and Subjects: A total of 329 girls from a prospective United Kingdom birth cohort study provided blood samples at mean age 8.1 yr (range, 8.0–8.5) for hormone measurements and were followed longitudinally to establish age at menarche. Main Outcome Measures: Fasting plasma levels of IGF-I, androstenedione, dehydroepiandrosterone sulfate (DHEAS), leptin, insulin, IGF binding protein-1, and SHBG were measured. Age at menarche was reported by questionnaire and categorized as before 12.0, 12.0–13.0, or later than 13 yr. Results: Earlier menarche was associated with greater body weight, height, and body mass index at age 8 yr (all P-trend <0.001). Before adjustment for body size, earlier menarche was associated with higher levels of IGF-I, androstenedione, DHEAS, leptin, and fasting insulin, and with lower levels of IGF binding protein-1 and SHBG at age 8 yr (all P < 0.01). After adjustment for body mass index and height at age 8 yr, only IGF-I (P = 0.004), androstenedione (P = 0.01), and DHEAS (P = 0.01) remained associated with earlier menarche. Conclusions: Associations between higher levels of IGF-I and adrenal androgens at age 8 yr with earlier menarche, independent of body size, support functional roles of these hormones in regulating puberty timing in girls. Higher levels of these hormones reported in children who exhibited rapid weight gain during infancy may indicate their role in developmental pathways leading to earlier sexual maturation.",
"title": "Higher Levels of IGF-I and Adrenal Androgens at Age 8 Years Are Associated with Earlier Age at Menarche in Girls"
},
{
"docid": "MED-2211",
"text": "BACKGROUND: China is increasingly facing the challenge of control of the growing burden of non-communicable diseases. We assessed the epidemiology of Alzheimer's disease and other forms of dementia in China between 1990, and 2010, to improve estimates of the burden of disease, analyse time trends, and inform health policy decisions relevant to China's rapidly ageing population. METHODS: In our systematic review we searched for reports of Alzheimer's disease or dementia in China, published in Chinese and English between 1990 and 2010. We searched China National Knowledge Infrastructure, Wanfang, and PubMed databases. Two investigators independently assessed case definitions of Alzheimer's disease and dementia: we excluded studies that did not use internationally accepted case definitions. We also excluded reviews and viewpoints, studies with no numerical estimates, and studies not done in mainland China. We used Poisson regression and UN demographic data to estimate the prevalence (in nine age groups), incidence, and standardised mortality ratio of dementia and its subtypes in China in 1990, 2000, and 2010. FINDINGS: Our search returned 12,642 reports, of which 89 met the inclusion criteria (75 assessed prevalence, 13 incidence, and nine mortality). In total, the included studies had 340,247 participants, in which 6357 cases of Alzheimer's disease were recorded. 254,367 people were assessed for other forms of dementia, of whom 3543 had vascular dementia, frontotemporal dementia, or Lewy body dementia. In 1990 the prevalence of all forms of dementia was 1·8% (95% CI 0·0-44·4) at 65-69 years, and 42·1% (0·0-88·9) at age 95-99 years. In 2010 prevalence was 2·6% (0·0-28·2) at age 65-69 years and 60·5% (39·7-81·3) at age 95-99 years. The number of people with dementia in China was 3·68 million (95% CI 2·22-5·14) in 1990, 5·62 million (4·42-6·82) in 2000, and 9·19 million (5·92-12·48) in 2010. In the same period, the number of people with Alzheimer's disease was 1·93 million (1·15-2·71) in 1990, 3·71 million (2·84-4·58) people in 2000, and 5·69 million (3·85-7·53) in 2010. The incidence of dementia was 9·87 cases per 1000 person-years, that of Alzheimer's disease was 6·25 cases per 1000 person-years, that of vascular dementia was 2·42 cases per 1000 person-years, and that of other rare forms of dementia was 0·46 cases per 1000 person-years. We retrieved mortality data for 1032 people with dementia and 20,157 healthy controls, who were followed up for 3-7 years. The median standardised mortality ratio was 1·94:1 (IQR 1·74-2·45). INTERPRETATION: Our analysis suggests that previous estimates of dementia burden, based on smaller datasets, might have underestimated the burden of dementia in China. The burden of dementia seems to be increasing faster than is generally assumed by the international health community. Rapid and effective government responses are needed to tackle dementia in low-income and middle-income countries. FUNDING: Nossal Institute of Global Health (University of Melbourne, Australia), the National 12th Five-Year Major Projects of China, National Health and Medical Research Council Australia-China Exchange Fellowship, Importation and Development of High-Calibre Talents Project of Beijing Municipal Institutions, and the Bill & Melinda Gates Foundation. Copyright © 2013 Elsevier Ltd. All rights reserved.",
"title": "Epidemiology of Alzheimer's disease and other forms of dementia in China, 1990-2010: a systematic review and analysis."
},
{
"docid": "MED-2977",
"text": "OBJECTIVE—Whereas limited and inconsistent findings have been reported on the relation between dietary cholesterol or egg consumption and fasting glucose, no previous study has examined the association between egg consumption and type 2 diabetes. This project sought to examine the relation between egg intake and the risk of type 2 diabetes in two large prospective cohorts. RESEARCH DESIGN AND METHODS—In this prospective study, we used data from two completed randomized trials: 20,703 men from the Physicians' Health Study I (1982–2007) and 36,295 women from the Women's Health Study (1992–2007). Egg consumption was ascertained using questionnaires, and we used the Cox proportional hazard model to estimate relative risks of type 2 diabetes. RESULTS—During mean follow-up of 20.0 years in men and 11.7 years in women, 1,921 men and 2,112 women developed type 2 diabetes. Compared with no egg consumption, multivariable adjusted hazard ratios for type 2 diabetes were 1.09 (95% CI 0.87–1.37), 1.09 (0.88–1.34), 1.18 (0.95–1.45), 1.46 (1.14–1.86), and 1.58 (1.25–2.01) for consumption of <1, 1, 2–4, 5–6, and ≥7 eggs/week, respectively, in men (P for trend <0.0001). Corresponding multivariable hazard ratios for women were 1.06 (0.92–1.22), 0.97 (0.83–1.12), 1.19 (1.03–1.38), 1.18 (0.88–1.58), and 1.77 (1.28–2.43), respectively (P for trend <0.0001). CONCLUSIONS—These data suggest that high levels of egg consumption (daily) are associated with an increased risk of type 2 diabetes in men and women. Confirmation of these findings in other populations is warranted.",
"title": "Egg Consumption and Risk of Type 2 Diabetes in Men and Women"
},
{
"docid": "MED-3848",
"text": "BACKGROUND: Epidemiologic studies that examined whether lignans, the most important class of phytoestrogens in the Western diet, protect against breast cancer have yielded inconsistent results. OBJECTIVE: In this study, we conducted meta-analyses on the association between lignans and breast cancer risk. DESIGN: We performed a systematic MEDLINE search to identify epidemiologic studies published between 1997 and August 2009. We calculated pooled risk estimates (REs) for total lignan exposure, dietary lignan intake, enterolignan exposure, and blood or urine concentrations of enterolactone and according to menopausal and estrogen receptor (ER) status of tumors. RESULTS: We included 21 studies (11 prospective cohort studies and 10 case-control studies) in the meta-analyses. Lignan exposure was not associated with an overall breast cancer risk (RE: 0.92; 95% CI: 0.81, 1.02; P for heterogeneity = 0.004). However, in postmenopausal women, high lignan intake was associated with a significant reduced risk of breast cancer (13 studies; RE: 0.86; 95% CI: 0.78, 0.94; P for heterogeneity = 0.32). Breast cancer risk was also inversely associated with enterolignan exposure (4 studies; RE: 0.84; 95% CI: 0.71, 0.97) but not with blood or urine enterolactone concentrations. The associations were not significantly different between ER-status subgroups (6 studies). CONCLUSIONS: High lignan exposure may be associated with a reduced breast cancer risk in postmenopausal women. Additional work is warranted to clarify the association between lignan exposure and breast cancer risk.",
"title": "Meta-analyses of lignans and enterolignans in relation to breast cancer risk."
},
{
"docid": "MED-2978",
"text": "Diets high in protein have shown positive effects on short-term weight reduction and glycaemic control. However, the understanding of how dietary macronutrient composition relates to long-term risk of type 2 diabetes is limited. The aim of the present study was to examine intakes of macronutrients, fibre and protein sources in relation to incident type 2 diabetes. In total, 27 140 individuals, aged 45-74 years, from the population-based Malmö Diet and Cancer cohort, were included. Dietary data were collected with a modified diet history method, including registration of cooked meals. During 12 years of follow-up, 1709 incident type 2 diabetes cases were identified. High protein intake was associated with increased risk of type 2 diabetes (hazard ratio (HR) 1.27 for highest compared with lowest quintile; 95 % CI 1.08, 1.49; P for trend = 0.01). When protein consumption increased by 5 % of energy at the expense of carbohydrates (HR 1.20; 95 % CI 1.09, 1.33) or fat (HR 1.21; 95 % CI 1.09, 1.33), increased diabetes risk was observed. Intakes in the highest quintiles of processed meat (HR 1.16; 95 % CI 1.00, 1.36; P for trend = 0.01) and eggs (HR 1.21; 95 % CI 1.04, 1.41; P for trend = 0.02) were associated with increased risk. Intake of fibre-rich bread and cereals was inversely associated with type 2 diabetes (HR 0.84; 95 % CI 0.73, 0.98; P for trend = 0.004). In conclusion, results from the present large population-based prospective study indicate that high protein intake is associated with increased risk of type 2 diabetes. Replacing protein with carbohydrates may be favourable, especially if fibre-rich breads and cereals are chosen as carbohydrate sources.",
"title": "High intakes of protein and processed meat associate with increased incidence of type 2 diabetes."
},
{
"docid": "MED-3832",
"text": "Oestrogen is an important determinant of breast cancer risk. Oestrogen-mimicking plant compounds called phytoestrogens can bind to oestrogen receptors and exert weak oestrogenic effects. Despite this activity, epidemiological studies suggest that the incidence of breast cancer is lower in countries where the intake of phytoestrogens is high, implying that these compounds may reduce breast cancer risk, and possibly have an impact on survival. Isoflavones and lignans are the most common phytoestrogens in the diet. In this article, we present findings from human observational and intervention studies related to both isoflavone and lignan exposure and breast cancer risk and survival. In addition, the clinical implications of these findings are examined in the light of a growing dietary supplement market. An increasing number of breast cancer patients seek to take supplements together with their standard treatment in the hope that these will either prevent recurrence or treat their menopausal symptoms. Observational studies suggest a protective effect of isoflavones on breast cancer risk and the case may be similar for increasing lignan consumption although evidence so far is inconsistent. In contrast, short-term intervention studies suggest a possible stimulatory effect on breast tissue raising concerns of possible adverse effects in breast cancer patients. However, owing to the dearth of human studies investigating effects on breast cancer recurrence and survival the role of phytoestrogens remains unclear. So far, not enough clear evidence exists on which to base guidelines for clinical use, although raising patient awareness of the uncertain effect of phytoestrogens is recommended.",
"title": "Do phytoestrogens reduce the risk of breast cancer and breast cancer recurrence? What clinicians need to know."
},
{
"docid": "MED-3798",
"text": "The Moos Menstrual Distress Questionnaire (MMDQ) was completed by thirty healthy premenopausal women randomized into one of two sets of weight-maintaining diets, those with a ratio of polyunsaturated to saturated fatty acids (P/S ratio) of 1.0 and those with a P/S ratio of 0.3. After a baseline interval of one menstrual cycle, both groups were fed a high fat diet (40% energy from fat) for four menstrual cycles per subject, followed by a similar interval on a low fat diet (20% energy from fat). There were no significant differences in self-reported menstrual symptoms between the two P/S groups. During both menses and the premenstrual week of the low fat dietary period there were significant decreases in self-reported symptoms associated with water retention. A decrease in symptoms in the group labelled \"arousal\" during the rest of the menstrual cycle was also reported.",
"title": "Influence of dietary fat on self-reported menstrual symptoms."
},
{
"docid": "MED-3448",
"text": "Iodine is a suspected risk factor for thyroid cancer. Seaweed accounts for about 80% of Japanese people's iodine intake. We examined the association between seaweed consumption and the risk of thyroid cancer in Japanese women. Women participating in the Japan Public Health Center-based Prospective Study (n=52 679; age: 40-69 years) were followed up for a mean of 14.5 years; 134 new thyroid cancer cases, including 113 papillary carcinoma cases, were identified. Seaweed consumption was assessed using a food-frequency questionnaire and divided into three categories: 2 days/week or less (reference); 3-4 days/week; and almost daily. The Cox proportional hazards model was applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Seaweed consumption was clearly associated with an increased risk of papillary carcinoma (HR for almost daily consumption compared with 2 days/week or less=1.71; 95% CI: 1.01-2.90; trend P=0.04). After stratification for menopausal status, an increased risk was observed in postmenopausal women (papillary carcinoma HR for almost daily consumption compared with 2 days/week or less=3.81, 95% CI: 1.67-8.68; trend P<0.01), but not in premenopausal women (HR=0.91, 95% CI: 0.44-1.91; trend P=0.76). This study identified a positive association between seaweed consumption and the risk of thyroid cancer (especially for papillary carcinoma) in postmenopausal women.",
"title": "Seaweed consumption and the risk of thyroid cancer in women: the Japan Public Health Center-based Prospective Study."
},
{
"docid": "MED-1332",
"text": "Background The definition of incident type 2 diabetes varies across studies; hence, the actual incidence of type 2 diabetes in Japan is unclear. Here, we reviewed the various definitions of incident type 2 diabetes used in previous epidemiologic studies and estimated the diabetes incidence rate in Japan. Methods We searched for related literature in the MEDLINE, EMBASE, and Ichushi databases through September 2012. Two reviewers selected studies that evaluated incident type 2 diabetes in the Japanese population. Results From 1824 relevant articles, we included 33 studies with 386,803 participants. The follow-up period ranged from 2.3 to 14 years and the studies were initiated between 1980 and 2003. The random-effects model indicated that the pooled incidence rate of diabetes was 8.8 (95% confidence interval, 7.4–10.4) per 1000 person-years. We observed a high degree of heterogeneity in the results (I2 = 99.2%; p < 0.001), with incidence rates ranging from 2.3 to 52.6 per 1000 person-years. Three studies based their definition of incident type 2 diabetes on self-reports only, 10 on laboratory data only, and 20 on self-reports and laboratory data. Compared with studies defining diabetes using laboratory data (n = 30; pooled incidence rate = 9.6; 95% confidence interval = 8.3–11.1), studies based on self-reports alone tended to show a lower incidence rate (n = 3; pooled incidence rate = 4.0; 95% confidence interval = 3.2–5.0; p for interaction < 0.001). However, stratified analyses could not entirely explain the heterogeneity in the results. Conclusions Our systematic review and meta-analysis indicated the presence of a high degree of heterogeneity, which suggests that there is a considerable amount of uncertainty regarding the incidence of type 2 diabetes in Japan. They also suggested that laboratory data may be important for the accurate estimation of the incidence of type 2 diabetes.",
"title": "Incidence of Type 2 Diabetes in Japan: A Systematic Review and Meta-Analysis"
},
{
"docid": "MED-4749",
"text": "For the first time in the field of steroid residues in humans, demonstration of 19-norandrosterone (19-NA: 3alpha-hydroxy-5alpha-estran-17-one) and 19-noretiocholanolone (19-NE: 3alpha-hydroxy-5beta-estran-17-one) excretion in urine subsequent to boar consumption is reported. Three male volunteers agreed to consume 310 g of tissues from the edible parts (meat, liver, heart and kidney) of a boar. The three individuals delivered urine samples before and during 24 h after meal intake. After deconjugation of phase II metabolites, purification and specific derivatisation of target metabolites, the urinary extracts were analysed by mass spectrometry. Identification was carried out using measurements obtained by gas chromatography/high resolution mass spectrometry (GC/HRMS) (R = 7000) and liquid chromatography/tandem mass spectrometry (LC/MS/MS) (positive electrospray ionisation (ESI+)). Quantification was realised using a quadrupole mass filter. 19-NA and 19-NE concentrations in urine reached 3.1 to 7.5 microg/L nearby 10 hours after boar tissue consumption. Levels returned to endogenous values 24 hours after. These two steroids are usually exploited to confirm the exogenous administration of 19-nortestosterone (19-NT: 17beta-hydroxyestr-4-en-3-one), especially in the antidoping field. We have thus proved that eating tissues of non-castrated male pork (in which 17beta-nandrolone is present) might induce some false accusations of the abuse of nandrolone in antidoping. Copyright 2000 John Wiley & Sons, Ltd.",
"title": "Consequence of boar edible tissue consumption on urinary profiles of nandrolone metabolites. I. Mass spectrometric detection and quantification of ..."
},
{
"docid": "MED-1540",
"text": "A number of studies have evaluated the health of vegetarians. Others have studied the health effects of foods that are preferred or avoided by vegetarians. The purpose of this review is to look critically at the evidence on the health effects of vegetarian diets and to seek possible explanations where results appear to conflict. There is convincing evidence that vegetarians have lower rates of coronary heart disease, largely explained by low LDL cholesterol, probable lower rates of hypertension and diabetes mellitus, and lower prevalence of obesity. Overall, their cancer rates appear to be moderately lower than others living in the same communities, and life expectancy appears to be greater. However, results for specific cancers are much less convincing and require more study. There is evidence that risk of colorectal cancer is lower in vegetarians and in those who eat less meat; however, results from British vegetarians presently disagree, and this needs explanation. It is probable that using the label “vegetarian” as a dietary category is too broad and that our understanding will be served well by dividing vegetarians into more descriptive subtypes. Although vegetarian diets are healthful and are associated with lower risk of several chronic diseases, different types of vegetarians may not experience the same effects on health.",
"title": "Vegetarian diets: what do we know of their effects on common chronic diseases?"
},
{
"docid": "MED-3800",
"text": "OBJECTIVE: To review the current management of women with breast pain. OPTIONS: The effect of various treatment modes and health practices, including medications, was considered for the management of both cyclical and noncyclical breast pain. OUTCOMES: Effective and timely management of the woman with breast pain and improved quality of life. EVIDENCE: A literature search was performed to identify reports published in English between 1975 and July 2003 using MEDLINE and Cochrane Database of Systematic Reviews. VALUES: Levels of evidence, as outlined, have been determined using the criteria outlined by the Canadian Task Force on the Periodic Health Examination. Participants were the principal authors: a clinical dietitian, a surgeon oncologist, and a nurse. BENEFITS, HARMS, AND COSTS: Utilizing the information will increase knowledge, enabling a consistent approach, which will reduce the number of ineffective interventions and ensure appropriate use medications. VALIDATION: Comparison has been made with management protocols in the literature, but no clinical guidelines have been located. No formal clinical testing has taken place. SPONSOR: The Society of Obstetricians and Gynaecologists of Canada (SOGC). Work on these guidelines was initiated by team members to fill a need for practice guidelines at Winnipeg Regional Health Authority Breast Health Centre, Winnipeg, MB. RECOMMENDATIONS: 1. Education and reassurance is an integral part of the management of mastalgia and should be the first-line treatment. (II-1 A) 2. The use of a well-fitting bra that provides good support should be considered for the relief of cyclical and noncyclical mastalgia. (II-3 B) 3. A change in dose, formulation, or scheduling should be considered for women on HRT. HRT may be discontinued if appropriate. (III C) 4. Women with breast pain should not be advised to reduce caffeine intake. (1 E) 5. Vitamin E should not be considered for the treatment of mastalgia. (1 E) 6. There is presently insufficient evidence to recommend the use of evening primrose oil (EPO) in the treatment of breast pain. (II-2 C) 7. Flaxseed should be considered as a first-line treatment for cyclical mastalgia. (I A) 8. Topical non-steroidal anti-inflammatory gel, such as diclofenac 2% in pluronic lethicin organogel, should be considered for pain control for localized treatment of mastalgia. (I A) 9. Tamoxifen 10 mg daily or danazol 200 mg daily should be considered when first-line treatments are ineffective. (I A) 10. Mastectomy or partial mastectomy should not be considered an effective treatment for mastalgia. (III E).",
"title": "Mastalgia."
},
{
"docid": "MED-4096",
"text": "A variety of statistics are used to quantify the burden (occurrence and outcome) of cancer generally and of breast cancer specifically. When undertaking any cancer control program, understanding these statistics, their source, and their quality is important for assessing the current situation, allocating resources to different control strategies, and evaluating progress. Two core statistics are the cancer incidence rate and the cancer mortality rate, which provide estimates of the average risk of acquiring and of dying from the disease, respectively. About 16% of the world's population is covered by registration systems that produce cancer incidence statistics, while mortality data are available for about 29%. Breast cancer incidence and mortality vary considerably by world region. In general, the incidence is high (greater than 80 per 100,000) in developed regions of the world and low (less than 30 per 100,000), though increasing, in developing regions; the range of mortality rates is much less (approximately 6-23 per 100,000) because of the more favorable survival of breast cancer in (high-incidence) developed regions. The incidence of breast cancer is increasing almost everywhere. This unfavorable trend is due in part to increases in risk factors (decreased childbearing and breast-feeding, increased exogenous hormone exposure, and detrimental dietary and lifestyle changes, including obesity and less physical activity). On the other hand, mortality is now decreasing in many high-risk countries due to a combination of intensified early detection efforts and the introduction of mammographic screening, resulting in the diagnosis of more small, early stage tumors, and advances in treatment.",
"title": "Use of statistics to assess the global burden of breast cancer."
},
{
"docid": "MED-3799",
"text": "Modifiable factors, including diet, might alter breast cancer risk. We used the WHI Dietary Modification (DM) trial to test the effect of the intervention on risk of benign proliferative breast disease, a condition associated with increased risk of and considered to be on the pathway to invasive breast cancer. The WHI DM trial was a randomized, controlled, primary prevention trial conducted in 40 US clinical centers from 1993–2005. 48,835 postmenopausal women, aged 50–79 years, without prior breast cancer, were enrolled. Participants were randomly assigned to the DM intervention group or to the comparison group. The intervention was designed to reduce total dietary fat intake to 20% of total energy intake, and to increase fruit and vegetable intake to ≥5 servings/day and intake of grain products to ≥6 servings/day, but resulted in smaller, albeit significant changes in practice. Participants had biennial mammograms and regular clinical breast exams. We identified women who reported breast biopsies free of cancer, obtained the histologic sections, and subjected them to standardized central review. During follow-up (average, 7.7 years), 570 incident cases of benign proliferative breast disease were ascertained in the intervention group and 793 in the comparison group. The hazard ratio for the association between DM and benign proliferative breast disease was 1.09 (95%CI, 0.98–1.23). Risk varied by levels of baseline total vitamin D intake but it varied little by levels of other baseline variables. These results suggest that a modest reduction in fat intake and increase in fruit, vegetable, and grain intake does not alter the risk of benign proliferative breast disease.",
"title": "Low-fat dietary pattern and risk of benign proliferative breast disease: a randomized, controlled dietary modification trial"
},
{
"docid": "MED-3443",
"text": "Incidence of the metabolic syndrome is increasing worldwide, with notable exceptions of some Asian countries where seaweeds are commonly consumed. 13 men (mean age 47.4+/-9.9 yr) and 14 women (average age 45.6+/-12.2 yr) with at least one symptom of the metabolic syndrome were recruited in Quito Ecuador to a randomized double-blinded placebo-controlled trial. Subjects were assigned to either Group 1 (1 m placebo, followed by 1 m 4 g/d seaweed [Undaria pinnatifida]) or Group 2 (1 m of 4 g/d seaweed, followed by 1 m of 6 g/d of seaweed). Blood pressure, weight, waist circumference, inflammation biomarkers, and lipids were measured monthly. Repeated measures analysis of variance with Tukey's multiple comparison tests were used for statistical analysis. In Group 2, systolic blood pressure decreased 10.5 mmHg after a month of 6 g/d seaweed (95% CI: 4.1, 16.8 mmHg; p<0.05), primarily in subjects with high-normal baseline blood pressure. Waist circumference changed only for women participants, with a 2.4 cm decrease in Group 1 after treatment with placebo (95% CI: 1.0, 3.7 cm; p<0.01). In Group 2, women had a mean decrease of 2.1 cm after 4 g/d (95% CI: 0.4, 3.7 cm; p<0.05) and a further 1.8 cm decrease after 1 m 6 g/d seaweed (95 % CI: 0.1, 3.4, p<0.05). No other changes were observed. Consumption of 4 to 6 g/d seaweed, typical for most people in Japan, may be associated with low metabolic syndrome prevalence.",
"title": "Could dietary seaweed reverse the metabolic syndrome?"
},
{
"docid": "MED-4440",
"text": "BACKGROUND: Contrary to earlier clinical studies suggesting that soy may promote breast tumor growth, two recent studies show that soy-containing foods are not adversely related to breast cancer prognosis. We examined, using data from the Women's Healthy Eating and Living (WHEL) study, the effect of soy intake on breast cancer prognosis. METHODS: Three thousand eighty-eight breast cancer survivors, diagnosed between 1991 and 2000 with early-stage breast cancer and participating in WHEL, were followed for a median of 7.3 years. Isoflavone intakes were measured postdiagnosis by using a food frequency questionnaire. Women self-reported new outcome events semiannually, which were then verified by medical records and/or death certificates. HRs and 95% CIs representing the association between either a second breast cancer event or death and soy intake were computed, adjusting for study group and other covariates, using the delayed entry Cox proportional hazards model. RESULTS: As isoflavone intake increased, risk of death decreased (P for trend = 0.02). Women at the highest levels of isoflavone intake (>16.3 mg isoflavones) had a nonsignificant 54% reduction in risk of death. CONCLUSION: Our study is the third epidemiologic study to report no adverse effects of soy foods on breast cancer prognosis. IMPACT: These studies, taken together, which vary in ethnic composition (two from the United States and one from China) and by level and type of soy consumption, provide the necessary epidemiologic evidence that clinicians no longer need to advise against soy consumption for women with a diagnosis of breast cancer. ©2011 AACR.",
"title": "Soy food consumption and breast cancer prognosis."
},
{
"docid": "MED-3853",
"text": "PURPOSE: Lignans--plant-derived compounds with estrogen-dependent and -independent anticarcinogenic properties--have been associated with postmenopausal breast cancer risk, but data are limited regarding their effect on survival. Dietary lignans are metabolized to enterolignans, which are subsequently absorbed and become bioavailable. PATIENTS AND METHODS: We assessed the prognosis of 1,140 postmenopausal patients with breast cancer age 50 to 74 years who were diagnosed between 2002 and 2005. Vital status through the end of 2009 was ascertained via local population registries, and deaths were verified by death certificates. Information on recurrences and secondary tumors was verified by clinical records and attending physicians. Associations of postdiagnostic serum enterolactone (a biomarker for dietary lignans) with overall survival and distant disease-free survival were assessed by using Cox proportional hazards models stratified by age at diagnosis and adjusted for prognostic factors. RESULTS: Median enterolactone levels for deceased patients and those still alive were 17.0 and 21.4 nmol/L, respectively. During a median of 6.1 years of follow-up after diagnosis, 162 deaths were confirmed. Higher serum enterolactone levels were associated with significantly reduced hazard ratios (HRs) for death (HR per 10 nmol/L increment, 0.94; P = .04; HR for the highest quartile, 0.58; 95% CI, 0.34 to 0.99). For distant disease, HR was 0.94 per 10 nmol/L increment (P = .08) and 0.62 (95% CI, 0.35 to 1.09) for the highest quartile. The highest quartile of serum enterolactone was associated with a significantly reduced risk of death only for estrogen receptor-negative tumors (HR, 0.27; 95% CI, 0.08 to 0.87) but not for estrogen receptor-positive tumors (HR, 0.91; 95% CI, 0.45 to 1.84: P for heterogeneity = .09). CONCLUSION: Postmenopausal patients with breast cancer who have high serum enterolactone levels may have better survival.",
"title": "Serum enterolactone and prognosis of postmenopausal breast cancer."
},
{
"docid": "MED-3250",
"text": "The purpose of this study was to determine whether a single LDL apheresis would improve impaired endothelium-dependent dilation of the coronary artery in patients with hypercholesterolemia. Hypercholesterolemia is associated with impaired endothelial function, and human studies using cholesterol-lowering drugs indicate that endothelial function in the coronary arteries improves with reduction of serum LDL cholesterol over 6 to 12 months. The internal diameter of the left coronary artery and the coronary blood flow were measured by intracoronary Doppler-wire measurement and quantitative angiography before and immediately after a single LDL apheresis in a population of 15 patients with familial hypercholesterolemia. Endothelium-dependent vasodilation was assessed by intracoronary infusion of acetylcholine (1, 10, and 50 microg/min), and endothelium-independent vasodilation was assessed by intracoronary bolus infusion of isosorbide dinitrate (2.5 mg) or papaverine (10 mg). A single 3-hour LDL apheresis reduced serum LDL cholesterol by an average of 86.6 +/- 1.7%. After the LDL apheresis, the changes in the coronary artery diameter and coronary blood flow in response to an infusion of 50 microg/min of acetylcholine increased significantly compared to the pre-apheresis values (from -19.7 +/- 4.8 to -2.9 +/- 3.0% [P < 0.01] and from 80.7 +/- 27.6 to 155.3 +/- 23.5% [P < 0.01], respectively). The LDL apheresis did not significantly change the response of either parameter to infusion with isosorbide dinitrate or papaverine. The endothelial function of the epicardial coronary artery and the coronary microvasculature improved in hypercholesterolemic patients after only a single LDL apheresis, a procedure that markedly reduces the serum level of LDL cholesterol. Copyright 2004 Wiley-Liss, Inc.",
"title": "Improvement of endothelium-dependent coronary vasodilation after a single LDL apheresis in patients with hypercholesterolemia."
},
{
"docid": "MED-3793",
"text": "OBJECTIVES: To determine cross-cultural and other effects on women's experiences of premenstrual symptoms and their impact on activities of daily life (ADL). STUDY DESIGN: Cross-sectional survey. Sample A total of 7226 women aged 15-49 recruited by random sampling with approximately 400 each from France, Germany, Hungary, Italy, Spain, UK, Brazil, Mexico, Hong Kong, Pakistan and Thailand. Approximately 1000 women in Japan and Korea and 500 Australian women were found using Internet panels. MAIN OUTCOME MEASURES: Questionnaire of 23 premenstrual symptoms, sociodemographic and lifestyle variables, ADL and women's knowledge of premenstrual terms. RESULTS: The most prevalent symptoms were abdominal bloating, cramps or abdominal pain, irritability, mastalgia and joint/muscle/back pains. Severity of symptoms was directly proportional to duration (number of affected cycles) (R = 0.78). A linear model found that symptom prevalence (duration × severity) was associated with age (linear and quadratic effects), parity, current smoking and country. Premenstrual physical and mental symptom domains had similar negative effects on ADL. Impact on ADL was affected by education and exercise participation. Women's knowledge of the terms premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) varied by symptom intensity, age, education and country. CONCLUSIONS: Four of the five most prevalent premenstrual symptoms were physical. There was a great deal of similarities of women's experiences of these symptoms across countries and regions. Women's knowledge of PMS terms is highly dependent on the country in which they live.",
"title": "Global study of women's experiences of premenstrual symptoms and their effects on daily life."
},
{
"docid": "MED-3982",
"text": "OBJECTIVE: To test the claim that pet ownership reduces cardiovascular risk. DESIGN: Community survey. PARTICIPANTS: 2528 adults aged 40-44 years and 2551 aged 60-64 years who lived in the Australian Capital Territory and Queanbeyan, New South Wales, and were drawn randomly from the Australian electoral roll in 2000 and 2001. MAIN OUTCOME MEASURES: Sociodemographic measures, including pet ownership, and measures of physical health (including body mass index [BMI], alcohol and cigarette consumption, and levels of physical activity). Two readings of diastolic and systolic blood pressure were also taken. RESULTS: While pet owners and non-pet owners had similar levels of systolic blood pressure, those with pets had significantly higher diastolic blood pressure. Pet owners also had higher BMI and were more likely to smoke. While those with pets undertook more mild physical activity, they continued to have significantly higher diastolic blood pressure after controlling for hypertensive risk factors. CONCLUSIONS: In this study, we found no evidence that pet ownership per se is associated with cardiovascular health benefits. Rather, pet owners had higher diastolic blood pressure than those without pets. It is likely that this increased health risk is linked to other hypertensive risk factors that are only indirectly associated with pet ownership.",
"title": "Pet ownership and risk factors for cardiovascular disease: another look."
},
{
"docid": "MED-4776",
"text": "Tea (Camellia sinensis, Theaceae) and tea polyphenols have been studied for the prevention of chronic diseases, including obesity. Obesity currently affects >20% of adults in the United States and is a risk factor for chronic diseases such as type II diabetes, cardiovascular disease, and cancer. Given this increasing public health concern, the use of dietary agents for the prevention of obesity would be of tremendous benefit. Whereas many laboratory studies have demonstrated the potential efficacy of green or black tea for the prevention of obesity, the underlying mechanisms remain unclear. The results of human intervention studies are mixed and the role of caffeine has not been clearly established. Finally, there is emerging evidence that high doses of tea polyphenols may have adverse side effects. Given that the results of scientific studies on dietary components, including tea polyphenols, are often translated into dietary supplements, understanding the potential toxicities of the tea polyphenols is critical to understanding their potential usefulness in preventing obesity. In this review, we will critically evaluate the evidence for the prevention of obesity by tea, discuss the relevance of proposed mechanisms in light of tea polyphenol bioavailability, and review the reports concerning the toxic effects of high doses of tea polyphenols and the implication that this has for the potential use of tea for the prevention of obesity. We hope that this review will expose areas for further study and encourage research on this important public health issue.",
"title": "Laboratory, Epidemiological, and Human Intervention Studies Show That Tea (Camellia sinensis) May Be Useful in the Prevention of Obesity"
},
{
"docid": "MED-4886",
"text": "OBJECTIVES: Previous research has demonstrated that patients with prostate cancer participating in the Prostate Cancer Lifestyle Trial had a reduction in prostate-specific antigen (PSA) levels, inhibition of LNCaP cell growth, and fewer prostate cancer-related clinical events at the end of 1 year compared with controls. The aim of this study was to examine the clinical events in this trial during a 2-year period. METHODS: The Prostate Cancer Lifestyle Trial was a 1-year randomized controlled clinical trial of 93 patients with early-stage prostate cancer (Gleason score <7, PSA 4-10 ng/mL) undergoing active surveillance. The patients in the experimental arm were encouraged to adopt a low-fat, plant-based diet, to exercise and practice stress management, and to attend group support sessions. The control patients received the usual care. RESULTS: By 2 years of follow-up, 13 of 49 (27%) control patients and 2 of 43 (5%) experimental patients had undergone conventional prostate cancer treatment (radical prostatectomy, radiotherapy, or androgen deprivation, P < .05). No differences were found between the groups in other clinical events (eg, cardiac), and no deaths occurred. Three of the treated control patients but none of the treated experimental patients had a PSA level of >or=10 ng/mL, and 1 treated control patient but no treated experimental patients had a PSA velocity of >2 ng/mL/y before treatment. No significant differences were found between the untreated experimental and untreated control patients in PSA change or velocity at the end of 2 years. CONCLUSIONS: Patients with early-stage prostate cancer choosing active surveillance might be able to avoid or delay conventional treatment for at least 2 years by making changes in their diet and lifestyle.",
"title": "Clinical events in prostate cancer lifestyle trial: results from two years of follow-up."
},
{
"docid": "MED-1330",
"text": "AIMS: To systematically review trends in diabetes mellitus (DM) prevalence in adults in China over the last 10 years and to identify the determinants of these trends. METHODS: A systematic search was conducted for studies published between 2000 and 2010. Studies reporting DM prevalence were included if they met the pre-determined criteria. The prevalence estimates and reported determinants of these studies were compared. RESULTS: Twenty-five manuscripts, reporting on 22 studies, were selected for inclusion in the review. There has been an increase in DM prevalence from 2.6% to 9.7% in China over the past decade. DM prevalence is strongly associated with age and is higher in urban residents compared with rural populations. Some studies found a difference in DM prevalence between males and females, but this finding was not consistent. Other commonly reported associations with DM included family history, obesity and hypertension. CONCLUSION: Over the period of 2000-2010, we identify a significant increase in DM prevalence at the national level. It is important for all levels of government to develop more effective strategies to prevent and manage this rising diabetes epidemic. There is also an important need for more large-scale studies of diabetes in the western and central regions of China. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.",
"title": "Diabetes prevalence and determinants in adults in China mainland from 2000 to 2010: a systematic review."
},
{
"docid": "MED-5124",
"text": "Background Reduction in dietary cholesterol is recommended to prevent cardiovascular disease (CVD). Although eggs are important sources of cholesterol and other nutrients, limited and inconsistent data are available on the effects of egg consumption on the risk of CVD and mortality. Objectives To examine the association between egg consumption and the risk of CVD and mortality. Design Prospective cohort study of 21,327 participants from the Physicians' Health Study I. Egg consumption was assessed using a simple abbreviated food questionnaire. We used Cox regression to estimate relative risks. Results After an average follow up of 20 years, a total of 1,550 new myocardial infarction (MI), 1,342 incident strokes, and 5,169 deaths occurred in this cohort. Egg consumption was not associated with incident MI or stroke in a multivariable Cox regression. In contrast, adjusted hazard ratios (95% CI) for mortality were 1.0 (reference), 0.94 (0.87-1.02), 1.03 (0.95-1.11), 1.05 (0.93-1.19), and 1.23 (1.11-1.36) for egg consumption of <1, 1, 2-4, 5-6, and 7+ per week, respectively, (p for trend <0.0001). This association was stronger among diabetic subjects with a 2-fold increased risk of death comparing the highest to the lowest category of egg consumption than non-diabetic subjects (HR: 1.22 (1.09-1.35) (p for interaction 0.09). Conclusions Our data suggest that infrequent egg consumption does not influence the risk of CVD and only confers a modest increased risk for total mortality in male physicians. In addition, egg consumption was positively related to mortality and such relation was stronger among diabetic subjects in this selective population.",
"title": "Egg Consumption and Cardiovascular Disease and Mortality The Physicians' Health Study"
},
{
"docid": "MED-3445",
"text": "A population-based case-control interview study was designed to test the hypothesis that dietary iodine or the consumption of goitrogenic vegetables increases the risk of thyroid cancer. A total of 191 histologically confirmed cases (64 percent female) and 441 matched controls from five ethnic groups in Hawaii were available for analysis. Among women, intake of seafood (especially shellfish), harm ha (a fermented fish sauce), and dietary iodine were associated with an increased risk of cancer, whereas consumption of goitrogenic (primarily cruciferous) vegetables was associated with a decreased risk. Non-dietary risk factors included miscarriage (especially at first pregnancy), use of fertility drugs, family history of thyroid disease, obesity, and work as a farm laborer. The odds ratio for the combined effect of a high iodine intake and a first-pregnancy miscarriage was 4.8 (95 percent confidence interval [CI] = 1.2-19.2); and for high iodine intake and use of fertility drugs 7.3 (95 percent CI = 1.5-34.5). Among men, positive associations were found for obesity, work as a farm laborer, and a past history of benign thyroid disease. Although this study identified several dietary and non-dietary risk factors for thyroid cancer, it could not fully explain the exceptionally high incidence rates among Filipino women in Hawaii.",
"title": "An epidemiologic study of thyroid cancer in Hawaii."
},
{
"docid": "MED-1795",
"text": "Objective To determine whether individual fruits are differentially associated with risk of type 2 diabetes. Design Prospective longitudinal cohort study. Setting Health professionals in the United States. Participants 66 105 women from the Nurses’ Health Study (1984-2008), 85 104 women from the Nurses’ Health Study II (1991-2009), and 36 173 men from the Health Professionals Follow-up Study (1986-2008) who were free of major chronic diseases at baseline in these studies. Main outcome measure Incident cases of type 2 diabetes, identified through self report and confirmed by supplementary questionnaires. Results During 3 464 641 person years of follow-up, 12 198 participants developed type 2 diabetes. After adjustment for personal, lifestyle, and dietary risk factors of diabetes, the pooled hazard ratio of type 2 diabetes for every three servings/week of total whole fruit consumption was 0.98 (95% confidence interval 0.96 to 0.99). With mutual adjustment of individual fruits, the pooled hazard ratios of type 2 diabetes for every three servings/week were 0.74 (0.66 to 0.83) for blueberries, 0.88 (0.83 to 0.93) for grapes and raisins, 0.89 (0.79 to 1.01) for prunes, 0.93 (0.90 to 0.96) for apples and pears, 0.95 (0.91 to 0.98) for bananas, 0.95 (0.91 to 0.99) for grapefruit, 0.97 (0.92 to 1.02) for peaches, plums, and apricots, 0.99 (0.95 to 1.03) for oranges, 1.03 (0.96 to 1.10) for strawberries, and 1.10 (1.02 to 1.18) for cantaloupe. The pooled hazard ratio for the same increment in fruit juice consumption was 1.08 (1.05 to 1.11). The associations with risk of type 2 diabetes differed significantly among individual fruits (P<0.001 in all cohorts). Conclusion Our findings suggest the presence of heterogeneity in the associations between individual fruit consumption and risk of type 2 diabetes. Greater consumption of specific whole fruits, particularly blueberries, grapes, and apples, is significantly associated with a lower risk of type 2 diabetes, whereas greater consumption of fruit juice is associated with a higher risk.",
"title": "Fruit consumption and risk of type 2 diabetes: results from three prospective longitudinal cohort studies"
},
{
"docid": "MED-3252",
"text": "It is commonly accepted that nutrition is one of the possible environmental factors involved in the pathogenesis of multiple sclerosis (MS), but its role as complementary MS treatment is unclear and largely disregarded. At present, MS therapy is not associated to a particular diet, probably due to lack of information on the effects of nutrition on the disease. To overcome the distrust of the usefulness of dietary control in MS and to encourage nutritional interventions in the course of the disease, it is necessary to assess the nature and the role of bioactive dietary molecules and their targets, and establish how a dietary control can influence cell metabolism and improve the wellness of MS patients. The aim of this review is to provide a rationale for a nutritional intervention in MS by evaluating at the molecular level the effects of dietary molecules on the inflammatory and autoimmune processes involved in the disease. Present data reveal that healthy dietary molecules have a pleiotropic role and are able to change cell metabolism from anabolism to catabolism and down-regulate inflammation by interacting with enzymes, nuclear receptors and transcriptional factors. The control of gut dysbiosis and the combination of hypo-caloric, low-fat diets with specific vitamins, oligoelements and dietary integrators, including fish oil and polyphenols, may slow-down the progression of the disease and ameliorate the wellness of MS patients. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "The molecular basis of nutritional intervention in multiple sclerosis: a narrative review."
},
{
"docid": "MED-1532",
"text": "Although substantial nutrition transition, characterized by an increased intake of energy, animal fat, and red meats, has occurred during the last several decades in East Asia, few studies have systematically evaluated temporal trends in cancer incidence or mortality among populations in this area. Therefore, we sought to investigate this question with tremendous public health implications. Data on mortality rates of cancers of the breast, colon, prostate, esophagus, and stomach for China (1988-2000), Hong Kong (1960-2006), Japan (1950-2006), Korea (1985-2006), and Singapore (1963-2006) were obtained from WHO. Joinpoint regression was used to investigate trends in mortality of these cancers. A remarkable increase in mortality rates of breast, colon, and prostate cancers and a precipitous decrease in those of esophageal and stomach cancers have been observed in selected countries (except breast cancer in Hong Kong) during the study periods. For example, the annual percentage increase in breast cancer mortality was 5.5% (95% confidence interval: 3.8, 7.3%) for the period 1985-1993 in Korea, and mortality rates for prostate cancer significantly increased by 3.2% (95% confidence interval: 3.0, 3.3%) per year from 1958 to 1993 in Japan. These changes in cancer mortality lagged ∼ 10 years behind the inception of the nutrition transition toward a westernized diet in selected countries or regions. There have been striking changes in mortality rates of breast, colon, prostate, esophageal, and stomach cancers in East Asia during the last several decades, which may be at least in part attributable to the concurrent nutrition transition.",
"title": "Trends in mortality from cancers of the breast, colon, prostate, esophagus, and stomach in East Asia: role of nutrition transition."
},
{
"docid": "MED-3249",
"text": "144 multiple sclerosis patients took a low-fat diet for 34 years. For each of three categories of neurological disability (minimum, moderate, severe) patients who adhered to the prescribed diet (less than or equal to 20 g fat/day) showed significantly less deterioration and much lower death rates than did those who consumed more fat than prescribed (greater than 20 g fat/day). The greatest benefit was seen in those with minimum disability at the start of the trial; in this group, when those who died from non-MS diseases were excluded from the analysis, 95% survived and remained physically active.",
"title": "Effect of low saturated fat diet in early and late cases of multiple sclerosis."
},
{
"docid": "MED-3795",
"text": "Mastalgia affects up to two-thirds of women at some time during their reproductive lives. It is usually benign, but thefear of underlying breast cancer is why many women present for evaluation. Mastalgia can be associated with premenstrual syndrome, fibrocystic breast disease, psychologic disturbance and, rarely, breast cancer. Occasionally, extramammary conditions, like Tietzie syndrome, present as mastalgia. A thorough clinical evaluation is required to assess the cause. The majority of women can be reassured after a clinical evaluation. Approximately 15% require pain-relieving therapy. Mechanical breast support; a low-fat, high-carbohydrate diet; and topical nonsteroidal antiinflammatory agents are reasonable first-line treatments. Hormonal agents, such as bromocriptine, tamoxifen and danazol, have all demonstrated efficacy in the treatment of mastalgia. Side effects, however, limit their extensive use. Danazol is the only FDA-approved hormonal treatment and is best used in cyclic form to limit the adverse effects. Lisuride maleate is a new agent recently studied for the treatment of mastalgia. Initial data on this medication are encouraging. Sixty percent of cyclic mastalgia recurs after treatment. Noncyclic mastalgia responds poorly to treatment but resolves spontaneously in up to 50% of cases.",
"title": "Mastalgia: a review of management."
},
{
"docid": "MED-2216",
"text": "BACKGROUND: Alzheimer's disease (AD) rates in Japan and developing countries have risen rapidly in recent years. Researchers have associated factors such as the Western diet, obesity, alcohol consumption, and smoking with risk of AD. OBJECTIVE: This paper evaluates whether the dietary transition might explain the rising trend of AD prevalence in Japan and in developing countries, evaluating other factors when possible. METHODS: This study used two approaches to see whether dietary or other changes could explain AD trends in Japan and developing countries. One approach involved comparing trends of AD in Japan with changes in national dietary supply factors, alcohol consumption, and lung cancer mortality rates from zero to 25 years before the prevalence data. The second compared AD prevalence values for eight developing countries with dietary supply factors from zero to 25 years before the prevalence data. RESULTS: For Japan, alcohol consumption, animal product, meat and rice supply, and lung cancer rates correlated highly with AD prevalence data, with the strongest correlation for a lag of 15-25 years. In the eight-country study, total energy and animal fat correlated highly with AD prevalence data, with a lag of 15-20 years. Mechanisms to explain the findings include increased obesity for the eight countries, and increases in cholesterol, saturated fat, and iron from increases in animal products and meat supply for Japan. CONCLUSION: Evidently AD rates will continue rising in non-Western countries for some time unless we address major risk factors involving diet, obesity, and smoking.",
"title": "Trends in diet and Alzheimer's disease during the nutrition transition in Japan and developing countries."
},
{
"docid": "MED-2215",
"text": "We investigated the relationship between animal product consumption and evidence of dementia in two cohort substudies. The first enrolled 272 California residents matched for age, sex, and zip code (1 vegan, 1 lacto-ovo-vegetarian, and 2 'heavy' meat eaters in each of 68 quartets). This design ensured a wide range of dietary exposure. The second included 2,984 unmatched subjects who resided within the Loma Linda, California area. All subjects were enrolled in the Adventist Health Study. The matched subjects who ate meat (including poultry and fish) were more than twice as likely to become demented as their vegetarian counterparts (relative risk 2.18, p = 0.065) and the discrepancy was further widened (relative risk 2.99, p = 0.048) when past meat consumption was taken into account. There was no significant difference in the incidence of dementia in the vegetarian versus meat-eating unmatched subjects. There was no obvious explanation for the difference between the two substudies, although the power of the unmatched sub-study to detect an effect of 'heavy' meat consumption was unexpectedly limited. There was a trend towards delayed onset of dementia in vegetarians in both substudies.",
"title": "The incidence of dementia and intake of animal products: preliminary findings from the Adventist Health Study."
},
{
"docid": "MED-3444",
"text": "Research on the relationship between iodine exposure and thyroid cancer risk is limited, and the findings are inconclusive. In most studies, fish/shellfish consumption has been used as a proxy measure of iodine exposure. The present study extends this research by quantifying dietary iodine exposure as well as incorporating a biomarker of long-term (1 year) exposure, i.e., from toenail clippings. This study is conducted in a multiethnic population with a wide variation in thyroid cancer incidence rates and substantial diversity in exposure. Women, ages 20-74, residing in the San Francisco Bay Area and diagnosed with thyroid cancer between 1995 and 1998 (1992-1998 for Asian women) were compared with women selected from the general population via random digit dialing. Interviews were conducted in six languages with 608 cases and 558 controls. The established risk factors for thyroid cancer were found to increase risk in this population: radiation to the head/neck [odds ratio (OR), 2.3; 95% confidence interval (CI), 0.97-5.5]; history of goiter/nodules (OR, 3.7; 95% CI, 2.5-5.6); and a family history of proliferative thyroid disease (OR, 2.5; 95% CI, 1.6-3.8). Contrary to our hypothesis, increased dietary iodine, most likely related to the use of multivitamin pills, was associated with a reduced risk of papillary thyroid cancer. This risk reduction was observed in \"low-risk\" women (i.e., women without any of the three established risk factors noted above; OR, 0.53; 95% CI, 0.33-0.85) but not in \"high-risk\" women, among whom a slight elevation in risk was seen (OR, 1.4; 95% CI, 0.56-3.4). However, no association with risk was observed in either group when the biomarker of exposure was evaluated. In addition, no ethnic differences in risk were observed. The authors conclude that iodine exposure appears to have, at most, a weak effect on the risk of papillary thyroid cancer.",
"title": "Iodine and thyroid cancer risk among women in a multiethnic population: the Bay Area Thyroid Cancer Study."
},
{
"docid": "MED-1529",
"text": "BACKGROUND: Few previous prospective studies have examined differences in incident ischemic heart disease (IHD) risk between vegetarians and nonvegetarians. OBJECTIVE: The objective was to examine the association of a vegetarian diet with risk of incident (nonfatal and fatal) IHD. DESIGN: A total of 44,561 men and women living in England and Scotland who were enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Oxford study, of whom 34% consumed a vegetarian diet at baseline, were part of the analysis. Incident cases of IHD were identified through linkage with hospital records and death certificates. Serum lipids and blood pressure measurements were available for 1519 non cases, who were matched to IHD cases by sex and age. IHD risk by vegetarian status was estimated by using multivariate Cox proportional hazards models. RESULTS: After an average follow-up of 11.6 y, there were 1235 IHD cases (1066 hospital admissions and 169 deaths). Compared with nonvegetarians, vegetarians had a lower mean BMI [in kg/m(2); -1.2 (95% CI: -1.3, -1.1)], non-HDL-cholesterol concentration [-0.45 (95% CI: -0.60, -0.30) mmol/L], and systolic blood pressure [-3.3 (95% CI: -5.9, -0.7) mm Hg]. Vegetarians had a 32% lower risk (HR: 0.68; 95% CI: 0.58, 0.81) of IHD than did nonvegetarians, which was only slightly attenuated after adjustment for BMI and did not differ materially by sex, age, BMI, smoking, or the presence of IHD risk factors. CONCLUSION: Consuming a vegetarian diet was associated with lower IHD risk, a finding that is probably mediated by differences in non-HDL cholesterol, and systolic blood pressure.",
"title": "Risk of hospitalization or death from ischemic heart disease among British vegetarians and nonvegetarians: results from the EPIC-Oxford cohort study."
},
{
"docid": "MED-1328",
"text": "BACKGROUND: In 2010, overweight and obesity were estimated to cause 3·4 million deaths, 3·9% of years of life lost, and 3·8% of disability-adjusted life-years (DALYs) worldwide. The rise in obesity has led to widespread calls for regular monitoring of changes in overweight and obesity prevalence in all populations. Comparable, up-to-date information about levels and trends is essential to quantify population health effects and to prompt decision makers to prioritise action. We estimate the global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013. METHODS: We systematically identified surveys, reports, and published studies (n=1769) that included data for height and weight, both through physical measurements and self-reports. We used mixed effects linear regression to correct for bias in self-reports. We obtained data for prevalence of obesity and overweight by age, sex, country, and year (n=19,244) with a spatiotemporal Gaussian process regression model to estimate prevalence with 95% uncertainty intervals (UIs). FINDINGS: Worldwide, the proportion of adults with a body-mass index (BMI) of 25 kg/m(2) or greater increased between 1980 and 2013 from 28·8% (95% UI 28·4-29·3) to 36·9% (36·3-37·4) in men, and from 29·8% (29·3-30·2) to 38·0% (37·5-38·5) in women. Prevalence has increased substantially in children and adolescents in developed countries; 23·8% (22·9-24·7) of boys and 22·6% (21·7-23·6) of girls were overweight or obese in 2013. The prevalence of overweight and obesity has also increased in children and adolescents in developing countries, from 8·1% (7·7-8·6) to 12·9% (12·3-13·5) in 2013 for boys and from 8·4% (8·1-8·8) to 13·4% (13·0-13·9) in girls. In adults, estimated prevalence of obesity exceeded 50% in men in Tonga and in women in Kuwait, Kiribati, Federated States of Micronesia, Libya, Qatar, Tonga, and Samoa. Since 2006, the increase in adult obesity in developed countries has slowed down. INTERPRETATION: Because of the established health risks and substantial increases in prevalence, obesity has become a major global health challenge. Not only is obesity increasing, but no national success stories have been reported in the past 33 years. Urgent global action and leadership is needed to help countries to more effectively intervene. FUNDING: Bill & Melinda Gates Foundation. Copyright © 2014 Elsevier Ltd. All rights reserved.",
"title": "Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global B..."
},
{
"docid": "MED-4680",
"text": "OBJECTIVE: To investigate associations between dietary intakes throughout childhood and age at menarche, a possible indicator of future risk of disease, in a contemporary cohort of British girls. DESIGN: Diet was assessed by FFQ at 3 and 7 years of age, and by a 3 d unweighed food diary at 10 years. Age at menarche was categorised as before or after 12 years 8 months, a point close to the median age in this cohort. SETTING: Bristol, South-West England. SUBJECTS: Girls (n 3298) participating in the Avon Longitudinal Study of Parents and Children. RESULTS: Higher energy intakes at 10 years were positively associated with the early occurrence of menarche, but this association was removed on adjusting for body size. Total and animal protein intakes at 3 and 7 years were positively associated with age at menarche ≤12 years 8 months (adjusted OR for a 1 sd increase in protein at 7 years: 1·14 (95 % CI 1·04, 1·26)). Higher PUFA intakes at 3 and 7 years were also positively associated with early occurrence of menarche. Meat intake at 3 and 7 years was strongly positively associated with reaching menarche by 12 years 8 months (OR for menarche in the highest v. lowest category of meat consumption at 7 years: 1·75 (95 % CI 1·25, 2·44)). CONCLUSIONS: These data suggest that higher intakes of protein and meat in early to mid-childhood may lead to earlier menarche. This may have implications for the lifetime risk of breast cancer and osteoporosis.",
"title": "Diet throughout childhood and age at menarche in a contemporary cohort of British girls."
},
{
"docid": "MED-1329",
"text": "White rice-based foods, which are high in refined carbohydrates, are widely consumed in China. A case-control study was conducted to investigate the association between white rice-based food consumption and the risk of ischemic stroke in the southern Chinese population. Information on diet and lifestyle was obtained from 374 incident ischemic stroke patients and 464 hospital-based controls. Logistic regression analyses were performed to assess the effects of rice-based foods on stroke risk. The mean weekly intake of rice foods appeared to be significantly higher in cases than in controls. Increased consumptions of cooked rice, congee, and rice noodle were associated with a higher risk for ischemic stroke after controlling for confounding factors. The corresponding adjusted odds ratios (with 95% confidence intervals) for the highest versus lowest intake level were 2.73 (1.31-5.69), 2.93 (1.68-5.13), and 2.03 (1.40-2.94), with significant dose-response relationships observed. The results provide evidence of a positive association between habitual rice food consumption and the risk of ischemic stroke in Chinese adults. Copyright © 2010 National Stroke Association. Published by Elsevier Inc. All rights reserved.",
"title": "White rice-based food consumption and ischemic stroke risk: a case-control study in southern China."
},
{
"docid": "MED-3791",
"text": "Experimental and epidemiological evidence suggest that a diet with dietary fat as low as 20% of kcal may be necessary to reduce the risk of breast cancer. Two groups of women, postmenopausal women treated for breast cancer and premenopausal women with cystic breast disease accompanied by cyclical mastaligia, participated in an intervention program to determine the feasibility of such a low-fat diet. After 3 mo of intervention both groups were consuming a low-fat diet; in the premenopausal groups serum estrogen levels decreased in response to the fat reduction. Other nutrition-education programs in research institutions, restaurants, and schools are attempting to influence the public's knowledge and behavior regarding the importance of dietary fat reduction.",
"title": "Recommendations for the prevention of chronic disease: the application for breast disease."
},
{
"docid": "MED-4098",
"text": "To investigate effects of dietary mushrooms and joint effects of mushrooms and green tea on breast cancer, a case-control study was conducted in southeast China in 2004-2005. The incident cases were 1,009 female patients aged 20-87 years with histologically confirmed breast cancer. The 1,009 age-matched controls were healthy women randomly recruited from outpatient breast clinics. Information on frequency and quantity of dietary intake of mushrooms and tea consumption, usual diet, and lifestyle were collected by face-to-face interview using a validated and reliable questionnaire. Compared with nonconsumers, the Odds ratios (Ors) were 0.36 (95% CI = 0.25-0.51) and 0.53 (0.38-0.73) for daily intake of >or=10 g fresh mushrooms and >or=4 g dried mushrooms, based on multivariate logistic regression analysis adjusting for established and potential confounders. There were dose-response relationships with significant tests for trend (p < 0.001). The inverse association was found in both pre- and postmenopausal women. Compared with those who consumed neither mushrooms nor green tea, the ORs were 0.11 (0.06-0.20) and 0.18 (0.11-0.29) for daily high intake of fresh and dried mushrooms combined with consuming beverages made from >or=1.05 g dried green tea leaves per day. The corresponding linear trends were statistically significant for joint effect (p < 0.001). We conclude that higher dietary intake of mushrooms decreased breast cancer risk in pre- and postmenopausal Chinese women and an additional decreased risk of breast cancer from joint effect of mushrooms and green tea was observed. More research is warranted to examine the effects of dietary mushrooms and mechanism of joint effects of phytochemicals on breast cancer.",
"title": "Dietary intakes of mushrooms and green tea combine to reduce the risk of breast cancer in Chinese women."
},
{
"docid": "MED-3441",
"text": "As modern lifestyles and new feeding habits settle in the world, noncommunicable diseases (NCDs) have evolved to be major causes of disability in developing as well as developed countries. As a concomitant effect, there is a growing interest in natural, healthy food and an increasing awareness of risk factors and determinants of disease. This chapter describes some nutritional facts about seaweeds, which have been used as food since ancient times in China, Japan, Egypt, and India and comments on the potential utilization of marine algae as functional foods. This concept and the description of metabolic syndrome are used as a basis to comprehension of seaweeds against two dreadful illnesses of our times: high blood pressure and cancer. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "Marine edible algae as disease preventers."
},
{
"docid": "MED-1321",
"text": "Phospholipids (PLs) are a major class of lipid in rice grain. Although PLs are only a minor nutrient compared to starch and protein, they may have both nutritional and functional significance. We have systemically reviewed the literature on the class, distribution and variation of PLs in rice, their relation to rice end-use quality and human health, as well as available methods for analytical profiling. Phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI) and their lyso forms are the major PLs in rice. The deterioration of PC in rice bran during storage was considered as a trigger for the degradation of rice lipids with associated rancid flavour in paddy and brown rice. The lyso forms in rice endosperm represent the major starch lipid, and may form inclusion complexes with amylose, affecting the physicochemical properties and digestibility of starch, and hence its cooking and eating quality. Dietary PLs have a positive impact on several human diseases and reduce the side-effects of some drugs. As rice has long been consumed as a staple food in many Asian countries, rice PLs may have significant health benefits for those populations. Rice PLs may be influenced both by genetic (G) and environmental (E) factors, and resolving G×E interactions may allow future exploitation of PL composition and content, thus boosting rice eating quality and health benefits for consumers. We have identified and summarised the different methods used for rice PL analysis, and discussed the consequences of variation in reported PL values due to inconsistencies between methods. This review enhances the understanding of the nature and importance of PLs in rice and outlines potential approaches for manipulating PLs to improve the quality of rice grain and other cereals. Copyright © 2013 Elsevier Ltd. All rights reserved.",
"title": "Phospholipids in rice: significance in grain quality and health benefits: a review."
},
{
"docid": "MED-1333",
"text": "New epidemiology confirms that glucose intolerance is a risk factor for pancreatic cancer, and that this association cannot be accounted for by an adverse impact of early pancreatic cancer on beta cell function. Previous reports indicate that risk for pancreatic cancer is increased in adult-onset diabetics. Since streptozotocin diabetes inhibits carcinogen-mediated induction of pancreatic cancer in hamsters, the most reasonable interpretation of these findings is that insulin (or some other beta cell product) acts as a promoter for pancreatic carcinogenesis. This view is consistent with a report that human pancreatic adenocarcinomas express insulin receptors that can stimulate mitosis; an additional possibility is that high insulin levels indirectly promote pancreatic carcinogenesis by boosting effective IGF-I activity via hepatic actions. In international ecologic epidemiology, pancreatic cancer rates correlate tightly with dietary intake of animal products; this may reflect the fact that vegan diets are associated with low diurnal insulin secretion. There is also suggestive evidence that macrobiotic vegan diets, which are low in glycemic index, may increase mean survival time in pancreatic cancer. However, other types of diets associated with decreased postprandial insulin response, such as high-protein diets or 'Mediterranean' diets high in oleic acid, may also have the potential for pancreatic cancer prevention. The huge increases of age-adjusted pancreatic cancer mortality in Japan and among African-Americans during the last century imply that pancreatic cancer is substantially preventable; a low-insulin-response diet coupled with exercise training, weight control, and smoking avoidance, commendable for a great many other reasons, may slash pancreatic cancer mortality dramatically. Copyright 2001 Harcourt Publishers Ltd.",
"title": "Insulin secretion as a determinant of pancreatic cancer risk."
},
{
"docid": "MED-4777",
"text": "The current practice of introducing phytochemicals to support the immune system or fight against diseases is based on centuries old traditions. Nutritional support is a recent advancement in the domain of diet-based therapies; green tea and its constituents are one of the important components of these strategies to prevent and cure various malignancies. The anti-carcinogenic and anti-mutagenic activities of green tea were highlighted some years ago suggesting that it could reduce the prevalence of cancer and even provide protection. The pharmacological actions of green tea are mainly attributed to polyphenols that includes epigallocatechin-3-gallate (EGCG), epicatechin, epicatechin-3-gallate, epigallocatechin. Green tea and its components effectively mitigate cellular damage arising due to oxidative stress. Green tea is supposed to enhance humoral and cell-mediated immunity, decreasing the risk of certain cancers, and may have certain advantage in treating inflammatory disorders. Much of the cancer chemopreventive properties of green tea are mediated by EGCG that induces apoptosis and promotes cell growth arrest, by altering the expression of cell cycle regulatory proteins, activating killer caspases, and suppressing nuclear factor kappa-B activation. Besides, it regulates and promotes IL-23 dependent DNA repair and stimulates cytotoxic T cells activities in a tumor microenvironment. It also blocks carcinogenesis by modulating the signal transduction pathways involved in cell proliferation, transformation, inflammation and metastasis. The review is intended to highlight the chemistry of green tea, its antioxidant potential, its immunopotentiating properties and mode of action against various cancer cell lines that showed its potential as a chemopreventive agent against colon, skin, lung, prostate, and breast cancer.",
"title": "Green tea: nature's defense against malignancies."
},
{
"docid": "MED-4216",
"text": "High levels of insulin-like growth factor 1 (IGF-1) are associated with increased risk of prostate cancer, whereas increased levels of some of its binding proteins (IGFBPs) seem to be protective. High intakes of dietary protein, especially animal and soy protein, appear to increase IGF-1. However, soy isoflavones have demonstrated anti-proliferative and apoptotic effects both in vitro and in vivo. We evaluated dietary intakes of total protein and soy isoflavones in relation to the IGF axis in prostate cancer patients making comprehensive lifestyle changes including a very low-fat vegan diet supplemented with soy protein (58 g/day). After one year, intervention group patients reported significantly higher intakes of dietary protein and soy isoflavones compared to usual-care controls (P < 0.001). IGF-1 increased significantly in both groups, whereas IGFBP-1 rose in the experimental group only (P < 0.01). Increases in vegetable protein over one year were associated with increases in IGFBP-1 among intervention group patients (P < 0.05). These results suggest that dietary protein and soy isoflavones, in the context of comprehensive lifestyle changes, may not significantly alter IGF-1. However, given the recent literature indicating that high intake of protein rich in essential amino acids (animal or soy protein) may increase IGF-1, it may be prudent for men with early stage prostate cancer not to exceed dietary protein recommendations.",
"title": "Relationship of dietary protein and soy isoflavones to serum IGF-1 and IGF binding proteins in the Prostate Cancer Lifestyle Trial."
},
{
"docid": "MED-1527",
"text": "Importance Some evidence suggests vegetarian dietary patterns may be associated with reduced mortality, but the relationship is not well established. Objective To evaluate the association between vegetarian dietary patterns and mortality. Design Prospective cohort study; mortality analysis by Cox proportional hazards regression, controlling for important demographic and lifestyle confounders. Setting Adventist Health Study 2 (AHS-2), a large North American cohort. Participants A total of 96 469 Seventh-day Adventist men and women recruited between 2002 and 2007, from which an analytic sample of 73 308 participants remained after exclusions. Exposures Diet was assessed at baseline by a quantitative food frequency questionnaire and categorized into 5 dietary patterns: nonvegetarian, semi-vegetarian, pesco-vegetarian, lacto-ovo–vegetarian, and vegan. Main Outcome and Measure The relationship between vegetarian dietary patterns and all-cause and cause-specific mortality; deaths through 2009 were identified from the National Death Index. Results There were 2570 deaths among 73 308 participants during a mean follow-up time of 5.79 years. The mortality rate was 6.05 (95% CI, 5.82–6.29) deaths per 1000 person-years. The adjusted hazard ratio (HR) for all-cause mortality in all vegetarians combined vs non-vegetarians was 0.88 (95% CI, 0.80–0.97). The adjusted HR for all-cause mortality in vegans was 0.85 (95% CI, 0.73–1.01); in lacto-ovo–vegetarians, 0.91 (95% CI, 0.82–1.00); in pesco-vegetarians, 0.81 (95% CI, 0.69–0.94); and in semi-vegetarians, 0.92 (95% CI, 0.75–1.13) compared with nonvegetarians. Significant associations with vegetarian diets were detected for cardiovascular mortality, noncardiovascular noncancer mortality, renal mortality, and endocrine mortality. Associations in men were larger and more often significant than were those in women. Conclusions and Relevance Vegetarian diets are associated with lower all-cause mortality and with some reductions in cause-specific mortality. Results appeared to be more robust in males. These favorable associations should be considered carefully by those offering dietary guidance.",
"title": "Vegetarian Dietary Patterns and Mortality in Adventist Health Study 2"
},
{
"docid": "MED-4747",
"text": "In contrast to the use of hormonal doping agents in sports to enhance the performance of athletes, in the livestock industry hormonal growth promoters (\"anabolics\") are used to increase the production of muscle meat. This leads to international disputes about the safety of meat originating from animals treated with such anabolics.As a consequence of the total ban in the EU of all hormonal active growth promoters (\"hormones\") in livestock production, in contrast to their legal use [e.g. of five such hormones (17beta-estradiol, testosterone, progesterone, trenbolone and zeranol) as small solid ear implants and two hormones as feed additives for feedlot heifers (melengestrol acetate) and for swine (ractopamine) in the USA], the regulatory controls also differ sharply between the EU and the USA.In the EU the treatment of slaughter animals is the regulatory offence that has to be controlled in inspection programs. In the USA testing for compliance of a regulatory maximum residue level in the edible product (muscle, fat, liver or kidney) is the purpose of the inspection program (if any).The EU inspection programs focus on sample materials that are more suitable for testing for banned substances, especially if the animals are still on the farm, such as urine and feces or hair. In the case of slaughtered animals, the more favored sample materials are bile, blood, eyes and sometimes liver. Only in rare occasions is muscle meat sampled. This happens only in the case of import controls or in monitoring programs of meat sampled in butcher shops or supermarkets.As a result, data on hormone concentrations in muscle meat samples from the EU market are very rare and are obtained in most cases from small programs on an ad hoc basis. EU data for natural hormones in meat are even rarer because of the absence of \"legal natural levels\" for these hormones in compliance testing. With the exception of samples from the application sites - in the EU the site of injection of liquid hormone preparations or the site of application of \"pour on\" preparations - the hormone concentrations observed in meat samples of illegally treated animals are typically in the range of a few micrograms per kilogram (ppb) down to a few tenths of a microgram per kilogram. In the EU dozens of illegal hormones are used and the number of active compounds is still expanding. Besides estrogenic, androgenic and progestagenic compounds also thyreostatic, corticosteroidal and beta-adrenergic compounds are used alone or in \"smart\" combinations.An overview is given of the compounds identified on the EU black market. An estimate is also given of the probability of consumption in the EU of \"highly\" contaminated meat from the application sites in cattle. Finally some data are presented on the concentration of estradiol in bovine meat from animals treated and not treated with hormone implants. These data are compared with the recent findings for estradiol concentrations in hen's eggs. From this comparison, the preliminary conclusion is that hen's eggs are the major source of 17alpha- and 17beta-estradiol in the consumer's daily \"normal\" diet.",
"title": "Hormonal growth promoting agents in food producing animals."
},
{
"docid": "MED-1319",
"text": "A comprehensive ecologic survey of dietary, life-style, and mortality characteristics of 65 counties in rural China showed that diets are substantially richer in foods of plant origin when compared with diets consumed in the more industrialized, Western societies. Mean intakes of animal protein (about one-tenth of the mean intake in the United States as energy percent), total fat (14.5% of energy), and dietary fiber (33.3 g/d) reflected a substantial preference for foods of plant origin. Mean plasma cholesterol concentration, at approximately 3.23-3.49 mmol/L, corresponds to this dietary life-style. The principal hypothesis under investigation in this paper is that chronic degenerative diseases are prevented by an aggregate effect of nutrients and nutrient-intake amounts that are commonly supplied by foods of plant origin. The breadth and consistency of evidence for this hypothesis was investigated with multiple intake-biomarker-disease associations, which were appropriately adjusted. There appears to be no threshold of plant-food enrichment or minimization of fat intake beyond which further disease prevention does not occur. These findings suggest that even small intakes of foods of animal origin are associated with significant increases in plasma cholesterol concentrations, which are associated, in turn, with significant increases in chronic degenerative disease mortality rates.",
"title": "Diet and chronic degenerative diseases: perspectives from China."
},
{
"docid": "MED-3442",
"text": "Gim (Porphyra sp.) and miyeok (Undaria pinnatifida) are the seaweeds most consumed by Koreans. We investigated the association between the intake of gim and miyeok and the risk of breast cancer in a case-control study. Cases were 362 women aged 30-65 years old, who were histologically confirmed to have breast cancer. Controls visiting the same hospital were matched to cases according to their age (sd 2 years) and menopausal status. Food intake was estimated by the quantitative FFQ with 121 items, including gim and miyeok. Conditional logistic regression analysis was used to obtain the OR and corresponding 95 % CI. The average intake and consumption frequency of gim in cases were lower than in controls. The daily intake of gim was inversely associated with the risk of breast cancer (5th v. 1st quintile, OR, 0.48; 95 % CI, 0.27, 0.86; P for trend, 0.026) after adjustment for potential confounders. After stratification analysis was performed according to menopausal status, premenopausal women (5th v. 1st quintile, OR, 0.44; 95 % CI, 0.24, 0.80; P for trend, 0.007) and postmenopausal women (5th v. 1st quintile, OR, 0.32; 95 % CI, 0.13, 0.80; P for trend, 0.06) showed similar inverse associations between gim intake and the risk of breast cancer after an adjustment for potential confounders except dietary factors. Miyeok consumption did not have any significant associations with breast cancer. These results suggest that high intake of gim may decrease the risk of breast cancer.",
"title": "A case-control study on seaweed consumption and the risk of breast cancer."
},
{
"docid": "MED-2212",
"text": "With the republication of Grant (18), the first paper providing epidemiologic evidence linking diet to the development of Alzheimer's disease (AD), it is an appropriate time to review the findings and hypotheses therein in light of the subsequent literature. The main findings, that dietary fat and energy in old age are high risk factors, while fish and cereals are risk-reduction factors, have been supported in various recent epidemiologic studies. Diet contributes to the development of AD through modulating oxidative stress and inflammation, which is also linked to oxidative stress, but may also arise from series 2 prostaglandins. Thus, as one ages, dietary modifications and additional supplements designed to reduce free radical production and inflammation provide a significant measure of reduction in risk for the development of AD.",
"title": "Dietary links to Alzheimer's disease: 1999 update."
},
{
"docid": "MED-2218",
"text": "OBJECTIVE: To determine prevalence of dementia and its subtypes in Japanese-American men and compare these findings with rates reported for populations in Japan and elsewhere. DESIGN AND SETTING: The Honolulu Heart Program is a prospective population-based study of cardiovascular disease established in 1965. Prevalence estimates were computed from cases identified at the 1991 to 1993 examination. Cognitive performance was assessed using standardized methods, instruments, and diagnostic criteria. PARTICIPANTS: Subjects were 3734 Japanese-American men (80% of surviving cohort) aged 71 through 93 years, living in the community or in institutions. MAIN OUTCOME MEASURES: Age-specific, age-standardized, and cohort prevalence estimates were computed for dementia (all cause) defined by 2 sets of diagnostic criteria and 4 levels of severity. Prevalence levels for Alzheimer disease and vascular dementia were also estimated. RESULTS: Dementia prevalence by Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised ranged from 2.1% in men aged 71 through 74 years to 33.4% in men aged 85 through 93 years. Age-standardized prevalence was 7.6%. Prevalence estimates for the cohort were 9.3% for dementia (all cause), 5.4% for Alzheimer disease (primary or contributing), and 4.2% for vascular dementia (primary or contributing). More than 1 possible cause was found in 26% of cases. The Alzheimer disease/vascular dementia ratio was 1.5 for cases attributed primarily to Alzheimer disease or vascular dementia. CONCLUSIONS: Prevalence of Alzheimer disease in older Japanese-American men in Hawaii appears to be higher than in Japan but similar to European-ancestry populations. Prevalence of vascular dementia appears to be slightly lower than in Japan, but higher than in European-ancestry populations. Further cross-national research with emphasis on standardized diagnostic methods is needed.",
"title": "Prevalence of dementia in older Japanese-American men in Hawaii: The Honolulu-Asia Aging Study."
},
{
"docid": "MED-1528",
"text": "A vegetarian diet generally includes plenty of vegetables and fruits, which are rich in phytochemicals, antioxidants, fiber, magnesium, vitamins C and E, Fe³⁺, folic acid and n-6 polyunsaturated fatty acid (PUFA), and is low in cholesterol, total fat and saturated fatty acid, sodium, Fe²⁺, zinc, vitamin A, B₁₂ and D, and especially n-3 PUFA. Mortality from all-cause, ischemic heart disease, and circulatory and cerebrovascular diseases was significantly lower in vegetarians than in omnivorous populations. Compared with omnivores, the incidence of cancer and type 2 diabetes was also significantly lower in vegetarians. However, vegetarians have a number of increased risk factors for non-communicable diseases such as increased plasma homocysteine, mean platelet volume and platelet aggregability compared with omnivores, which are associated with low intake of vitamin B₁₂ and n-3 PUFA. Based on the present data, it would seem appropriate for vegetarians to carefully design their diet, specifically focusing on increasing their intake of vitamin B₁₂ and n-3 PUFA to further reduce already low mortality and morbidity from non-communicable diseases. © 2013 Society of Chemical Industry.",
"title": "Effect of the vegetarian diet on non-communicable diseases."
},
{
"docid": "MED-1541",
"text": "We propose the hypothesis that a vegetarian diet reduces the risk of developing diabetes. Findings that have generated this hypothesis are from a population of 25,698 adult White Seventh-day Adventists identified in 1960. During 21 years of follow-up, the risk of diabetes as an underlying cause of death in Adventists was approximately one-half the risk for all US Whites. Within the male Adventist population, vegetarians had a substantially lower risk than non-vegetarians of diabetes as an underlying or contributing cause of death. Within both the male and female Adventist populations, the prevalence of self-reported diabetes also was lower in vegetarians than in non-vegetarians. The associations observed between diabetes and meat consumption were apparently not due to confounding by over- or under-weight, other selected dietary factors, or physical activity. All of the associations between meat consumption and diabetes were stronger in males than in females.",
"title": "Does a vegetarian diet reduce the occurrence of diabetes?"
},
{
"docid": "MED-3446",
"text": "Seaweed and soy foods are consumed daily in Japan, where breast cancer rates for postmenopausal women are significantly lower than in the West. Likely mechanisms include differences in diet, especially soy consumption, and estrogen metabolism. Fifteen healthy postmenopausal women participated in this double-blind trial of seaweed supplementation with soy challenge. Participants were randomized to 7 wk of either 5 g/d seaweed (Alaria) or placebo (maltodextrin). During wk 7, participants also consumed a daily soy protein isolate (2 mg isoflavones/kg body weight). After a 3-wk washout period, participants were crossed over to the alternate supplement schedule. There was an inverse correlation between seaweed dose (mg/kg body weight) and serum estradiol (E2) (seaweed-placebo = y = -2.29 x dose + 172.3; r = -0.70; P = 0.003), [corrected] which was linear across the range of weights. Soy supplementation increased urinary daidzein, glycitein, genistein, and O-desmethylangolensin (P = 0.0001) and decreased matairesinol and enterolactone (P < 0.05). Soy and seaweed plus soy (SeaSoy) increased urinary excretion of 2-hydroxyestrogen (2-OHE) (P = 0.0001) and the ratio of 2-OHE:16alpha-hydroxyestrone (16alphaOHE(1)) (P = 0.01). For the 5 equol excretors, soy increased urinary equol excretion (P = 0.0001); the combination of SeaSoy further increased equol excretion by 58% (P = 0.0001). Equol producers also had a 315% increase in 2:16 ratio (P = 0.001) with SeaSoy. Seaweed favorably alters estrogen and phytoestrogen metabolism and these changes likely include modulation of colonic bacteria.",
"title": "Dietary seaweed modifies estrogen and phytoestrogen metabolism in healthy postmenopausal women."
},
{
"docid": "MED-3792",
"text": "Basal serum prolactin and serum oestradiol-17-beta concentrations were measured four times during one menstrual cycle in 20 women with severe cyclical mastalgia and normal to slightly fibroadenotic breasts. A group of 10 normal women who had never experienced mastalgia served as controls. Basal serum prolactin was significantly elevated in patients compared to normals, although within the normal range. Serum oestradiol concentrations did not differ in the two groups and were also within the normal range. A significant positive correlation between oestradiol and prolactin was found in patients and normals, but with larger prolactin levels in patients. The results point towards a prolactin secretory hypersensitivity for oestradiol in patients with cyclical mastalgia. Prolactin is considered a central factor in the eliciting of cyclical mastalgia.",
"title": "Serum prolactin and oestradiol levels in women with cyclical mastalgia."
},
{
"docid": "MED-3797",
"text": "A double blind crossover trial of the prolactin inhibitor bromocriptine in painful benign breast disease is reported. Twenty-nine women with cyclical mastalgia and 11 with non-cyclical pain were treated with bromocriptine, 5 mg daily, and placebo over six menstrual cycels. Assessment of response to treatment was made by a linear analogue system and clinical examination together with plasma prolactin estimations. Bromocriptine produced a significant improvement in breast symptoms and a significant fall in prolactin levels in the cyclical pain group, but had no effect in the non-cyclical group. These results suggest that bromocriptine offers a new and effective approach in the management of cyclical breast pain.",
"title": "A double blind trial of the prolactin inhibitor bromocriptine in painful benign breast disease."
},
{
"docid": "MED-3955",
"text": "BACKGROUND Polybrominated Diphenyl Ethers (PBDEs), widely used as flame retardants since the 1970s, have exhibited endocrine disruption in experimental studies. Tetra- to hexa-BDE congeners are estrogenic, while hepta-BDE and 6-OH-BDE-47 are antiestrogenic. Most PBDEs also have antiandrogenic activity. It is not clear, however, whether PBDEs affect human reproduction. OBJECTIVES The analysis was designed to investigate the potential endocrine disruption of PBDEs on the age at menarche in adolescent girls. METHODS We analyzed the data from a sample of 271 adolescent girls (age 12–19 years) in the National Health and Nutrition Examination Survey (NHANES), 2003–2004. We estimated the associations between individual and total serum BDEs (BDE-28, -47, -99, -100, -153, and -154, lipid adjusted) and mean age at menarche. We also calculated the risk ratios (RRs) and 95% confidence intervals (CI) for menarche prior to age 12 years in relation to PBDE exposure. RESULTS The median total serum BDE concentration was 44.7 ng/g lipid. Higher serum PBDE concentrations were associated with slightly earlier ages at menarche. Each natural log unit of total BDEs was related to a change of −0.10 (95% CI: −0.33, 0.13) years of age at menarche and a RR of 1.60 (95% CI: 1.12, 2.28) for experiencing menarche before 12 years of age, after adjustment for potential confounders. CONCLUSION These data suggest high concentrations of serum PBDEs during adolescence are associated with a younger age of menarche.",
"title": "Serum PBDEs and Age at Menarche in Adolescent Girls: Analysis of the National Health and Nutrition Examination Survey 2003–2004"
},
{
"docid": "MED-1612",
"text": "Type II diabetic subjects were given 50 g protein, 50 g glucose, or 50 g glucose with 50 g protein as a single meal in random sequence. The plasma glucose and insulin response was determined over the subsequent 5 h. The plasma glucose area above the baseline following a glucose meal was reduced 34% when protein was given with the glucose. When protein was given alone, the glucose concentration remained stable for 2 h and then declined. The insulin area following glucose was only modestly greater than with a protein meal (97 +/- 35, 83 +/- 19 microU X h/ml, respectively). When glucose was given with protein, the mean insulin area was considerably greater than when glucose or protein was given alone (247 +/- 33 microU X h/ml). When various amounts of protein were given with 50 g glucose, the insulin area response was essentially first order. Subsequently, subjects were given 50 g glucose or 50 g glucose with 50 g protein as two meals 4 h apart in random sequence. The insulin areas were not significantly different for each meal but were higher when protein + glucose was given. After the second glucose meal the plasma glucose area was 33% less than after the first meal. Following the second glucose + protein meal the plasma glucose area was markedly reduced, being only 7% as large as after the first meal. These data indicate that protein given with glucose will increase insulin secretion and reduce the plasma glucose rise in at least some type II diabetic persons.",
"title": "Effect of protein ingestion on the glucose and insulin response to a standardized oral glucose load."
},
{
"docid": "MED-4750",
"text": "Androgenic steroids always exist in different animal tissues at trace level, with significant numbers of interfering compounds, which makes their determination difficult. To solve some of the problems in quantification of the natural steroids in those tissues, a new GC-MS method was developed in this study. By using a surrogate analyte approach, which was developed in the authors' previous studies, and extensive sample preparation procedure, which successfully eliminates many of the interfering compounds and resulting in a cleaner extract, accuracy, precision, sensitivity and selectivity of the method for the determination of steroids in complex matrices such as meat, liver and testis were improved. By aid of this method, the levels of androgens in different tissues of Iranian native cross-breed bulls and male sheep were determined. According to the results obtained in the present study, although the androgenic profile (contents and ratios of precursors and metabolites to the main hormones) is similar between the same tissues of both animals, the total androgenic content of each tissue is higher in the bull than the same tissue in male sheep. In addition, in both animals higher amount of androgens were found in liver in comparison with meat and testis.",
"title": "Assessment of endogenous androgen levels in meat, liver and testis of Iranian native cross-breed male sheep and bull by gas chromatography-mass spe..."
},
{
"docid": "MED-3983",
"text": "This study was aimed at determining the molecular epidemiology of rabies virus (RABV) circulating in Vietnam. Intra vitam samples (saliva and cerebrospinal fluid) were collected from 31 patients who were believed to have rabies and were admitted to hospitals in northern provinces of Vietnam. Brain samples were collected from 176 sick or furious rabid dogs from all over the country. The human and canine samples were subjected to reverse transcription-polymerase chain reaction analysis. The findings showed that 23 patients tested positive for RABV. Interestingly, 5 rabies patients did not have any history of dog or cat bites, but they had an experience of butchering dogs or cats, or consuming their meat. RABV was also detected in 2 of the 100 sick dogs from slaughterhouses. Molecular epidemiological analysis of 27 RABV strains showed that these viruses could be classified into two groups. The RABVs classified into Group 1 were distributed throughout Vietnam and had sequence similarity with the strains from China, Thailand, Malaysia, and the Philippines. However, the RABVs classified into Group 2 were only found in the northern provinces of Vietnam and showed high sequence similarity with the strain from southern China. This finding suggested the recent influx of Group 2 RABVs between Vietnam and China across the border. Although the incidence of rabies due to circulating RABVs in slaughterhouses is less common than that due to dog bite, the national program for rabies control and prevention in Vietnam should include monitoring of the health of dogs meant for human consumption and vaccination for workers at dog slaughterhouses. Further, monitoring of and research on the circulating RABVs in dog markets may help to determine the cause of rabies and control the spread of rabies in slaughterhouses in Vietnam.",
"title": "Molecular epidemiology of rabies virus in Vietnam (2006-2009)."
},
{
"docid": "MED-1531",
"text": "Observational and ecological studies are generally used to determine the presence of effect of cancer risk-modifying factors. Researchers generally agree that environmental factors such as smoking, alcohol consumption, poor diet, lack of physical activity, and low serum 25-hdyroxyvitamin D levels are important cancer risk factors. This ecological study used age-adjusted incidence rates for 21 cancers for 157 countries (87 with high-quality data) in 2008 with respect to dietary supply and other factors, including per capita gross domestic product, life expectancy, lung cancer incidence rate (an index for smoking), and latitude (an index for solar ultraviolet-B doses). The factors found to correlate strongly with multiple types of cancer were lung cancer (direct correlation with 12 types of cancer), energy derived from animal products (direct correlation with 12 types of cancer, inverse with two), latitude (direct correlation with six types, inverse correlation with three), and per capita gross national product (five types). Life expectancy and sweeteners directly correlated with three cancers, animal fat with two, and alcohol with one. Consumption of animal products correlated with cancer incidence with a lag time of 15–25 years. Types of cancer which correlated strongly with animal product consumption, tended to correlate weakly with latitude; this occurred for 11 cancers for the entire set of countries. Regression results were somewhat different for the 87 high-quality country data set and the 157-country set. Single-country ecological studies have inversely correlated nearly all of these cancers with solar ultraviolet-B doses. These results can provide guidance for prevention of cancer.",
"title": "A Multicountry Ecological Study of Cancer Incidence Rates in 2008 with Respect to Various Risk-Modifying Factors"
},
{
"docid": "MED-4748",
"text": "BACKGROUND: Adrenarche is the increase in adrenal androgen (AA) production starting in childhood. Until now, it has been unknown whether or not nutritional factors modulate adrenarche. OBJECTIVE: The objective was to examine whether body composition and certain dietary intakes are associated with AA production in children after accounting for urinary indicators of major adrenarche-related steroidogenic enzymes. DESIGN: Androgen and glucocorticoid metabolites were profiled by gas chromatography-mass spectrometry in 24-h urine samples of 137 healthy prepubertal children aged 3-12 y, for whom birth characteristics, growth velocity data, and 3-d weighed-diet record information were available. Associations of the sum of C19 metabolites (reflecting daily AA secretion) with nutritional factors [fat mass (FM), fat-free mass (FFM), nutrient intakes, glycemic index, and glycemic load] and AA-relevant estimates of steroidogenic enzyme were examined in stepwise multiple regression models adjusted for age, sex, urine volume, and total energy intake. Enzyme activity estimates were calculated by using specific urinary steroid metabolite ratios. RESULTS: Of the nutrition-relevant predictors, FM (P < 0.0001) explained most of the variation of AA secretion (R(2) = 5%). Animal protein intake was also positively associated with AA secretion (P < 0.05), which explained 1% of its variation. FFM (P = 0.1) and total protein intake (P = 0.05) showed positive trends. The difference in daily AA secretion between the lowest and highest quartile of FM was comparable to that between the lowest and highest estimated activity of one of the major steroidogenic enzymes. CONCLUSIONS: Body fat mass may relevantly influence prepubertal adrenarchal androgen status. In addition, animal protein intake may also make a small contribution to AA secretion in children.",
"title": "Body fat and animal protein intakes are associated with adrenal androgen secretion in children."
},
{
"docid": "MED-3984",
"text": "In recent years, the number of human rabies cases in the People’s Republic of China has increased during severe epidemics in 3 southern provinces (Guizhou, Guangxi, and Hunan). To analyze the causes of the high incidence of human rabies in this region, during 2005–2007, we collected 2,887 brain specimens from apparently healthy domestic dogs used for meat consumption in restaurants, 4 specimens from suspected rabid dogs, and 3 from humans with rabies in the 3 provinces. Partial nucleoprotein gene sequences were obtained from rabies-positive specimens. Phylogenetic relationships and distribution of viruses were determined. We infer that the spread of rabies viruses from high-incidence regions, particularly by long-distance movement or transprovincial translocation of dogs caused by human-related activities, may be 1 cause of the recent massive human rabies epidemics in southern China.",
"title": "Molecular Epidemiology of Rabies in Southern People’s Republic of China"
},
{
"docid": "MED-4097",
"text": "The identification of modifiable lifestyle factors that could reduce the risk of breast cancer is a research priority. Despite the enormous chemo preventive potential of green tea and compelling evidence from animal studies, its role in breast cancer development in humans is still unclear. Part of the uncertainty is related to the relatively small number of epidemiological studies on green tea and breast cancer and that the overall results from case-control studies and prospective cohort studies are discordant. In addition, the mechanisms by which green tea intake may influence risk of breast cancer in humans remains not well studied. We review the human studies that have evaluated the relationship between green tea intake and four biomarkers (sex steroid hormones, mammographic density, insulin-like growth factor, adiponectin) that are believed to be important in breast cancer development. Results from these biomarker studies are also inconclusive. Limitations of human studies and areas of further investigations are discussed.",
"title": "Green Tea and Breast Cancer"
},
{
"docid": "MED-1335",
"text": "AIMS: Diabetes rates are especially high in China. Risk of Type 2 diabetes increases with high intakes of white rice, a staple food of Chinese people. Ethnic differences in postprandial glycaemia have been reported. We compared glycaemic responses to glucose and five rice varieties in people of European and Chinese ethnicity and examined possible determinants of ethnic differences in postprandial glycaemia. METHODS: Self-identified Chinese (n = 32) and European (n = 31) healthy volunteers attended on eight occasions for studies following ingestion of glucose and jasmine, basmati, brown, Doongara(®) and parboiled rice. In addition to measuring glycaemic response, we investigated physical activity levels, extent of chewing of rice and salivary α-amylase activity to determine whether these measures explained any differences in postprandial glycaemia. RESULTS: Glycaemic response, measured by incremental area under the glucose curve, was over 60% greater for the five rice varieties (P < 0.001) and 39% greater for glucose (P < 0.004) amongst Chinese compared with Europeans. The calculated glycaemic index was approximately 20% greater for rice varieties other than basmati (P = 0.01 to 0.05). Ethnicity [adjusted risk ratio 1.4 (1.2-1.8) P < 0.001] and rice variety were the only important determinants of incremental area under the glucose curve. CONCLUSIONS: Glycaemic responses following ingestion of glucose and several rice varieties are appreciably greater in Chinese compared with Europeans, suggesting the need to review recommendations regarding dietary carbohydrate amongst rice-eating populations at high risk of diabetes. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.",
"title": "Glycaemic responses to glucose and rice in people of Chinese and European ethnicity."
},
{
"docid": "MED-4780",
"text": "OBJECTIVE: To examine the association between green tea consumption and tooth loss. METHODS: We analyzed cross-sectional data from the Ohsaki Cohort 2006 Study. Usable self-administered questionnaires about green tea consumption and tooth loss were returned from 25,078 persons (12,019 men and 13,059 women) aged 40 to 64 years in Japan. Multivariate logistic regression analysis was used to calculate odds ratios (ORs) for tooth loss using 3 cut-off points of 10, 20, and 25 teeth relative to each category of green tea consumption. RESULTS: Consumption of > or = 1 cup/day of green tea was significantly associated with decreased odds for tooth loss, and the association appeared to fit a threshold model. In men, the multivariate-adjusted ORs for tooth loss with a cut-off point of <20 teeth associated with different frequencies of green tea consumption were 1.00 (reference) for <1 cup/day, 0.82 (95% CI, 0.74-0.91) for 1-2 cups/day, 0.82 (95% CI, 0.73-0.92) for 3-4 cups/day, and 0.77 (95% CI, 0.66-0.89) for > or = 5 cups/day. The corresponding data for women and the results for cut-off points of 10 and 25 teeth were essentially the same. CONCLUSIONS: The present findings indicate an association of green tea consumption with decreased odds for tooth loss. Copyright 2010 Elsevier Inc. All rights reserved.",
"title": "Association between green tea consumption and tooth loss: cross-sectional results from the Ohsaki Cohort 2006 Study."
},
{
"docid": "MED-4912",
"text": "Rice is more elevated in arsenic than all other grain crops tested to date, with whole grain (brown) rice having higher arsenic levels than polished (white). It is reported here that rice bran, both commercially purchased and specifically milled for this study, have levels of inorganic arsenic, a nonthreshold, class 1 carcinogen, reaching concentrations of approximately 1 mg/kg dry weight, around 10-20 fold higher than concentrations found in bulk grain. Although pure rice bran is used as a health food supplement, perhaps of more concern is rice bran solubles, which are marketed as a superfood and as a supplement to malnourished children in international aid programs. Five rice bran solubles products were tested, sourced from the United States and Japan, and were found to have 0.61-1.9 mg/kg inorganic arsenic. Manufactures recommend approximately 20 g servings of the rice bran solubles per day, which equates to a 0.012-0.038 mg intake of inorganic arsenic. There are no maximum concentration levels (MCLs) set for arsenic or its species in food stuffs. EU and U.S. water regulations, set at 0.01 mg/L total or inorganic arsenic, respectively, are based on the assumption that 1 L of water per day is consumed, i.e., 0.01 mg of arsenic/ day. At the manufacturers recommended rice bran solubles consumption rate, inorganic arsenic intake exceeds 0.01 mg/ day, remembering that rice bran solubles are targeted at malnourished children and that actual risk is based on mg kg(-1) day(-1) intake.",
"title": "Inorganic arsenic in rice bran and its products are an order of magnitude higher than in bulk grain."
},
{
"docid": "MED-1334",
"text": "By 2002, China’s prevalence of overweight and obesity among adults was 18.9 percent and 2.9 percent, respectively. The Chinese traditional diet has been replaced by the “Western diet” and major declines in all phases of activity and increased sedentary activity as the main reasons explaining the rapid increase in overweight and obesity, bring major economic and health costs. The Nutrition Improvement Work Management Approach was released in 2010. Overweight and obesity prevention-related policies were added to national planning for disease prevention and control. The Guidelines for Prevention and Control of Overweight and Obesity of Chinese Adults and the School-age Children and Teenagers Overweight and Obesity Prevention and Control Guidelines in China were promulgated in 2003 and 2007, respectively. Few education programs have been implemented. Selected academic intervention research projects dominate with a focus on reducing child obesity and promoting healthier diets; increasing physical activity and reducing sedentary time; and facilitating changes in family, school, social, and cultural environments. Intervention samples are small and have not addressed the increasing rates of obesity throughout the entire population. Government provision of effective policy measures, multisectoral cooperation and increasing corporate social responsibility are keys to curb the trend toward overweight and obesity in China.",
"title": "Program and Policy Options for Preventing Obesity in China"
},
{
"docid": "MED-3801",
"text": "21 patients with severe persistent cyclical mastopathy of at least 5 years' duration were randomised to a control group who received general dietary advice or to an intervention group who were taught how to reduce the fat content of their diet to 15% of calories while increasing complex carbohydrate consumption to maintain caloric intake. Both groups were followed for 6 months with food records and measurement of plasma hormone and lipid levels. Severity of symptoms was recorded with daily diaries and patients were assessed at the beginning and end of the study by a physician who was unaware of their dietary regimen. After 6 months there was a significant reduction in the intervention group in the severity of premenstrual breast tenderness and swelling. Physical examination showed reduced breast swelling, tenderness, and nodularity in 6 of 10 patients in the intervention group and 2 of 9 patients in the control group.",
"title": "Effect of a low-fat high-carbohydrate diet on symptoms of cyclical mastopathy."
},
{
"docid": "MED-1331",
"text": "Many changes in diet and in physical activity are occurring simultaneously in the developing world. These diet shifts include large increases in energy density, in the proportion of the population consuming a high fat diet and in animal product intake. Animal source foods (ASF) play a major role in these diet shifts. This article documents the large shifts in the composition of diets and obesity across the developing world and notes that these changes are accelerating. Using China as a case study, evidence of the speeding up of this process is presented in descriptive and more rigorous dynamic longitudinal analysis. The implications of these changes for dietary and obesity patterns and cardiovascular disease are great. Indeed, developing countries are at a point where the prevalence of obesity is greater than that of undernutrition and concerns related to intake of saturated fat and energy imbalance must be considered more seriously by the agriculture sector. Current agriculture development policy in many developing countries focuses on livestock promotion and does not consider the potential adverse health consequences of this strategy. Although linkages between ASF intake and obesity cannot be established as clearly as they are for high ASF intakes, heart disease and cancer, the potential adverse health effects linked with an increased ASF intake should no longer be ignored.",
"title": "Dynamics of the nutrition transition toward the animal foods sector in China and its implications: a worried perspective."
},
{
"docid": "MED-1327",
"text": "Whole-grain and high fiber intakes are routinely recommended for prevention of vascular diseases; however, there are no comprehensive and quantitative assessments of available data in humans. The aim of this study was to systematically examine longitudinal studies investigating whole-grain and fiber intake in relation to risk of type 2 diabetes (T2D), cardiovascular disease (CVD), weight gain, and metabolic risk factors. We identified 45 prospective cohort studies and 21 randomized-controlled trials (RCT) between 1966 and February 2012 by searching the Cumulative Index to Nursing and Allied Health Literature, Cochrane, Elsevier Medical Database, and PubMed. Study characteristics, whole-grain and dietary fiber intakes, and risk estimates were extracted using a standardized protocol. Using random effects models, we found that compared with never/rare consumers of whole grains, those consuming 48-80 g whole grain/d (3-5 serving/d) had an ~26% lower risk of T2D [RR = 0.74 (95% CI: 0.69, 0.80)], ~21% lower risk of CVD [RR = 0.79 (95% CI: 0.74, 0.85)], and consistently less weight gain during 8-13 y (1.27 vs 1.64 kg; P = 0.001). Among RCT, weighted mean differences in post-intervention circulating concentrations of fasting glucose and total and LDL-cholesterol comparing whole-grain intervention groups with controls indicated significantly lower concentrations after whole-grain interventions [differences in fasting glucose: -0.93 mmol/L (95% CI: -1.65, -0.21), total cholesterol: -0.83 mmol/L (-1.23, -0.42); and LDL-cholesterol: -0.82 mmol/L (-1.31, -0.33)]. [corrected] Findings from this meta-analysis provide evidence to support beneficial effects of whole-grain intake on vascular disease prevention. Potential mechanisms responsible for whole grains' effects on metabolic intermediates require further investigation in large intervention trials.",
"title": "Greater whole-grain intake is associated with lower risk of type 2 diabetes, cardiovascular disease, and weight gain."
},
{
"docid": "MED-3843",
"text": "PURPOSE: Phytoestrogens are plant-derived, non-steroidal phytochemicals with anticarcinogenic potential. The major structural classes are the isoflavones and lignans. The aim of this study was to compare the effect of the plant-derived lignans secoisolariciresinol and matairesinol with the human lignans enterodiol and enterolactone as well as with 17β estradiol and tamoxifen on cell proliferation of breast carcinoma cell lines. METHODS: The influence of the lignans, 17β estradiol and tamoxifen on cell proliferation was determined using the BrdU test in MCF 7 and BT 20 cell lines. RESULTS: Enterodiol and enterolactone induced a stronger inhibition of cell growth in MCF 7 and BT 20 cells than secoisolariciresinol and matairesinol. The inhibition effects were less expressed in the BT 20 than in the MCF 7 cells. CONCLUSIONS: The human lignans enterodiol and enterolactone are more biologically active than their precursors secoisolariciresinol and matairesinol, and may be defined as the real drugs in cancer prevention.",
"title": "Antiproliferative activity of lignans against the breast carcinoma cell lines MCF 7 and BT 20."
},
{
"docid": "MED-2217",
"text": "OBJECTIVE: To determine the prevalence of AD and other dementias in a rural elderly Hindi-speaking population in Ballabgarh in northern India. DESIGN: The authors performed a community survey of a cohort of 5,126 individuals aged 55 years and older, 73.3% of whom were illiterate. Hindi cognitive and functional screening instruments, developed for and validated in this population, were used to screen the cohort. A total of 536 subjects (10.5%) who met operational criteria for cognitive and functional impairment and a random sample of 270 unimpaired control subjects (5.3%) underwent standardized clinical assessment for dementia using the Diagnostic and Statistical Manual of Mental Disorders-fourth edition diagnostic criteria, the Clinical Dementia Rating Scale (CDR), and National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable and possible AD. RESULTS: We found an overall prevalence rate of 0.84% (95% CI, 0.61 to 1.13) for all dementias with a CDR score of at least 0.5 in the population aged 55 years and older, and an overall prevalence rate of 1.36% (95% CI, 0.96 to 1.88) in the population aged 65 years and older. The overall prevalence rate for AD was 0.62% (95% CI, 0.43 to 0.88) in the population aged 55+ and 1.07% (95% CI, 0.72 to 1.53) in the population aged 65+. Greater age was associated significantly with higher prevalence of both AD and all dementias, but neither gender nor literacy was associated with prevalence. CONCLUSIONS: In this population, the prevalence of AD and other dementias was low, increased with age, and was not associated with gender or literacy. Possible explanations include low overall life expectancy, short survival with the disease, and low age-specific incidence potentially due to differences in the underlying distribution of risk and protective factors compared with populations with higher prevalence.",
"title": "Prevalence of Alzheimer's disease and other dementias in rural India: the Indo-US study."
},
{
"docid": "MED-3794",
"text": "OBJECTIVE: To test the hypothesis that a low-fat, vegetarian diet reduces dysmenorrhea and premenstrual symptoms by its effect on serum sex-hormone binding globulin concentration and estrogen activity. METHODS: In a crossover design, 33 women followed a low-fat, vegetarian diet for two menstrual cycles. For two additional cycles, they followed their customary diet while taking a supplement placebo pill. Dietary intake, serum sex-hormone binding globulin concentration, body weight, pain duration and intensity, and premenstrual symptoms were assessed during each study phase. RESULTS: Mean (+/- standard deviation [SD]) serum sex-hormone binding globulin concentration was higher during the diet phase (46.7 +/- 23.6 nmol/L) than during the supplement phase (39.3 +/- 19.8 nmol/L, P < .001). Mean (+/- SD) body weight was lower during the diet (66.1 +/- 11.3 kg) compared with the supplement phase (67.9 +/- 12.1 kg, P < .001). Mean dysmenorrhea duration fell significantly from baseline (3.9 +/- 1.7 days) to diet phase (2.7 +/- 1.9 days) compared with change from baseline to supplement phase (3.6 +/- 1.7 days, P < .01). Pain intensity fell significantly during the diet phase, compared with baseline, for the worst, second-worst, and third-worst days, and mean durations of premenstrual concentration, behavioral change, and water retention symptoms were reduced significantly, compared with the supplement phase. CONCLUSION: A low-fat vegetarian diet was associated with increased serum sex-hormone binding globulin concentration and reductions in body weight, dysmenorrhea duration and intensity, and premenstrual symptom duration. The symptom effects might be mediated by dietary influences on estrogen activity.",
"title": "Diet and sex-hormone binding globulin, dysmenorrhea, and premenstrual symptoms."
},
{
"docid": "MED-1318",
"text": "BACKGROUND: Rice consumption has been associated with risk of type 2 diabetes, but its relation with cardiovascular disease (CVD) is limited. OBJECTIVE: We examined the association between rice consumption and risk of CVD incidence and mortality in a Japanese population. DESIGN: This was a prospective study in 91,223 Japanese men and women aged 40-69 y in whom rice consumption was determined and updated from 3 self-administered food-frequency questionnaires, each 5 y apart. Follow-up for incidence was from 1990 to 2009 in cohort I and 1993 to 2007 in cohort II and for mortality was from 1990 to 2009 in cohort I and 1993 to 2009 in cohort II. HRs and 95% CIs of CVD incidence and mortality were calculated according to quintiles of cumulative average rice consumption. RESULTS: In 15-18 y of follow-up, we ascertained 4395 incident cases of stroke, 1088 incident cases of ischemic heart disease (IHD), and 2705 deaths from CVD. Rice consumption was not associated with risk of incident stroke or IHD; the multivariable HR (95% CI) in the highest compared with lowest rice consumption quintiles was 1.01 (0.90, 1.14) for total stroke and 1.08 (0.84, 1.38) for IHD. Similarly, there was no association between rice consumption and risk of mortality from CVD; the HR (95% CI) for mortality from total CVD was 0.97 (0.84, 1.13). There were no interactions with sex or effect modifications by body mass index for any endpoint. CONCLUSION: Rice consumption is not associated with risk of CVD morbidity or mortality. © 2014 American Society for Nutrition.",
"title": "Rice consumption is not associated with risk of cardiovascular disease morbidity or mortality in Japanese men and women: a large population-based, ..."
},
{
"docid": "MED-3447",
"text": "To investigate the chemopreventive effects of seaweed on breast cancer, we have been studying the relationship between iodine and breast cancer. We found earlier that the seaweed, wakame, showed a suppressive effect on the proliferation of DMBA (dimethylbenz(a)anthracene)-induced rat mammary tumors, possibly via apoptosis induction. In the present study, powdered mekabu was placed in distilled water, and left to stand for 24 h at 4 degrees C. The filtered supernatant was used as mekabu solution. It showed an extremely strong suppressive effect on rat mammary carcinogenesis when used in daily drinking water, without toxicity. In vitro, mekabu solution strongly induced apoptosis in 3 kinds of human breast cancer cells. These effects were stronger than those of a chemotherapeutic agent widely used to treat human breast cancer. Furthermore, no apoptosis induction was observed in normal human mammary cells. In Japan, mekabu is widely consumed as a safe, inexpensive food. Our results suggest that mekabu has potential for chemoprevention of human breast cancer.",
"title": "Seaweed prevents breast cancer?"
},
{
"docid": "MED-2214",
"text": "Summary Background 100 years after the first description, Alzheimer's disease is one of the most disabling and burdensome health conditions worldwide. We used the Delphi consensus method to determine dementia prevalence for each world region. Methods 12 international experts were provided with a systematic review of published studies on dementia and were asked to provide prevalence estimates for every WHO world region, for men and women combined, in 5-year age bands from 60 to 84 years, and for those aged 85 years and older. UN population estimates and projections were used to estimate numbers of people with dementia in 2001, 2020, and 2040. We estimated incidence rates from prevalence, remission, and mortality. Findings Evidence from well-planned, representative epidemiological surveys is scarce in many regions. We estimate that 24·3 million people have dementia today, with 4·6 million new cases of dementia every year (one new case every 7 seconds). The number of people affected will double every 20 years to 81·1 million by 2040. Most people with dementia live in developing countries (60% in 2001, rising to 71% by 2040). Rates of increase are not uniform; numbers in developed countries are forecast to increase by 100% between 2001 and 2040, but by more than 300% in India, China, and their south Asian and western Pacific neighbours. Interpretation We believe that the detailed estimates in this paper constitute the best currently available basis for policymaking, planning, and allocation of health and welfare resources.",
"title": "Global prevalence of dementia: a Delphi consensus study"
},
{
"docid": "MED-4778",
"text": "The methanolic extract of fresh tea leaves of Camellia sinensis L. (Theaceae) (CS) was assayed for its potential to inhibit enzymes with hydrolytic activity in Naja naja kaouthia Lesson (Elapidae) and Calloselasma rhodostoma Kuhl (Viperidae) venoms. These snake venom enzymes are responsible for the early effects of envenomation, such as local tissue damage and inflammation. The CS extract inhibited phospholipase A(2), proteases, hyaluronidase and L-amino acid oxidase in both venoms by in vitro neutralization and inhibited the hemorrhagic and the dermonecrotic activities of the venoms in vivo. It is suggested that the inhibitory potential of the CS extract against local tissue damage induced by snake venoms may be attributed to complexation and chelation between the venom proteins and the phenolic contents of the extract.",
"title": "Inhibitory effect of tea polyphenols on local tissue damage induced by snake venoms."
},
{
"docid": "MED-4785",
"text": "Purpose Soy isoflavones, structurally similar to endogenous estrogens, may affect breast cancer through both hormonally-mediated and non-hormonally related mechanisms. Although the effects of soy are not well understood, some breast cancer survivors increase their soy intake post-diagnosis in attempt to improve their prognosis. Therefore, we examined the role of soy isoflavone intake and the risk of breast cancer recurrence by hormone receptor status, menopausal status, and tamoxifen therapy. Materials and methods A cohort of 1954 female breast cancer survivors, diagnosed during 1997–2000, was prospective followed for 6.31 years and 282 breast cancer recurrences were ascertained. Isoflavone intake was assessed by mailing modified Block and supplemental soy food frequency questionnaires to participants, on average 23 months post-diagnosis. Risk of breast cancer recurrence, measured by hazard ratios (HR) and 95% confidence intervals (CI), was estimated using multivariable delayed-entry Cox proportional hazards models. Results Suggestive trends for a reduced risk of cancer recurrence were observed with increasing quintiles of daidzein and glycetin intake compared to no intake among postmenopausal women (P for trend: P = .08 for daidzein, P = .06 for glycetin) and among tamoxifen users (P = .10 for daidzein, P = .05 for glycetin). Among postmenopausal women treated with tamoxifen, there was an approximately 60% reduction in breast cancer recurrence comparing the highest to the lowest daidzein intakes (>1453 micrograms (µg)/day versus < 7.7 µg/day) (HR, 0.48; 95% CI, 0.21–0.79, P = .008). Conclusion Soy isoflavones consumed at levels comparable to those in Asian populations may reduce the risk of cancer recurrence in women receiving tamoxifen therapy and moreover, appears not to interfere with tamoxifen efficacy. Further confirmation is required in other large prospective studies before recommendations regarding soy intake can be issued to breast cancer survivors.",
"title": "Soy Isoflavones and Risk of Cancer Recurrence in a Cohort of Breast Cancer Survivors: Life After Cancer Epidemiology (LACE) Study"
},
{
"docid": "MED-4751",
"text": "The continued increase in incidence of some hormone-related cancers worldwide is of great concern. Although estrogen-like substances in the environment were blamed for this increase, the possible role of endogenous estrogens from food has not been widely discussed. We are particularly concerned about cows' milk, which contains a considerable quantity of estrogens. When we name cows' milk as one of the important routes of human exposure to estrogens, the general response of Western people is that \"man has been drinking cows' milk for around 2000 years without apparent harm.\" However, the milk that we are now consuming is quite different from that consumed 100 years ago. Unlike their pasture-fed counterparts of 100 years ago, modern dairy cows are usually pregnant and continue to lactate during the latter half of pregnancy, when the concentration of estrogens in blood, and hence in milk, increases. The correlation of incidence and mortality rates with environmental variables in worldwide countries provides useful clues to the etiology of cancer. In this study, we correlated incidence rates for breast, ovarian, and corpus uteri cancers (1993-97 from Cancer Incidence in Five Continents) with food intake (1961-97 from FAOSTAT) in 40 countries. Meat was most closely correlated with the breast cancer incidence (r=0.827), followed by milk (0.817) and cheese (0.751). Stepwise multiple-regression analysis (SMRA) identified meat as the factor contributing most greatly to the incidence of breast cancer ([R]=0.862). Milk was most closely correlated with the incidence of ovarian cancer (r=0.779), followed by animal fats (0.717) and cheese (0.697). SMRA revealed that milk plus cheese make the greatest contribution to the incidence of ovarian cancer ([R]=0.767). Milk was most closely correlated with corpus uteri cancer (r=0.814), followed by cheese (0.787). SMRA revealed that milk plus cheese make the most significant contribution to the incidence of corpus uteri cancer ([R]=0.861). In conclusion, increased consumption of animal-derived food may have adverse effects on the development of hormone-dependent cancers. Among dietary risk factors, we are most concerned with milk and dairy products, because the milk we drink today is produced from pregnant cows, in which estrogen and progesterone levels are markedly elevated.",
"title": "The possible role of female sex hormones in milk from pregnant cows in the development of breast, ovarian and corpus uteri cancers."
},
{
"docid": "MED-2213",
"text": "CONTEXT: Alzheimer disease (AD) represents a major and increasing public health problem. If populations were identified with significantly lower or higher incidence rates of AD, the search for risk factors in the genesis of AD could be greatly enhanced. OBJECTIVE: To compare incidence rates of dementia and AD in 2 diverse, elderly community-dwelling populations. DESIGN: The Indianapolis-Ibadan Dementia Project, a longitudinal, prospective population-based study consisting of a baseline survey (1992-1993) and 2 subsequent follow-up waves after 2 years (1994-1995) and 5 years (1997-1998). Each wave followed a 2-stage design, with an in-home screening interview followed by a full diagnostic workup of a subsample of participants based on screening performance. SETTING AND PARTICIPANTS: A total of 2459 community-dwelling Yoruba residents of Ibadan, Nigeria, without dementia, and 2147 community-dwelling African American residents of Indianapolis, Ind, without dementia (all aged 65 years or older). The cohorts were followed up for a mean of 5.1 years and 4.7 years, respectively. MAIN OUTCOME MEASURES: Incident cases of dementia and AD in each of the 2 populations. RESULTS: The age-standardized annual incidence rates were significantly lower among Yoruba than among African Americans for dementia (Yoruba, 1.35% [95% confidence interval [CI], 1.13%-1.56%]; African Americans, 3.24% [95% CI, 2.11%-4.38%]) and for AD (Yoruba, 1.15% [95% CI, 0.96%-1.35%]; African Americans, 2.52% [95% CI, 1.40%-3.64%]). CONCLUSION: This is the first report of incidence rate differences for dementia and AD in studies of 2 populations from nonindustrialized and industrialized countries using identical methods and the same group of investigators in both sites. Further explorations of these population differences may identify potentially modifiable environmental or genetic factors to account for site differences in dementia and AD.",
"title": "Incidence of dementia and Alzheimer disease in 2 communities: Yoruba residing in Ibadan, Nigeria, and African Americans residing in Indianapolis, I..."
},
{
"docid": "MED-3796",
"text": "Lignans are a group of phytochemicals shown to have weakly estrogenic and antiestrogenic properties. Two specific lignans, enterodiol and enterolactone, are absorbed after formation in the intestinal tract from plant precursors particularly abundant in fiber-rich food and are excreted in the urine. We evaluated the effect of the ingestion of flax seed powder, known to produce high concentrations of urinary lignans, on the menstrual cycle in 18 normally cycling women, using a balanced randomized cross-over design. Each subject consumed her usual omnivorous, low fiber (control) diet for 3 cycles and her usual diet supplemented with flax seed for another 3 cycles. The second and third flax cycles were compared to the second and third control cycles. Three anovulatory cycles occurred during the 36 control cycles, compared to none during the 36 flax seed cycles. Compared to the ovulatory control cycles, the ovulatory flax cycles were consistently associated with longer luteal phase (LP) lengths (mean +/- SEM, 12.6 +/- 0.4 vs. 11.4 +/- 0.4 days; P = 0.002). There were no significant differences between flax and control cycles for concentrations of either estradiol or estrone during the early follicular phase, midfollicular phase, or LP. Although flax seed ingestion had no significant effect on LP progesterone concentrations, the LP progesterone/estradiol ratios were significantly higher during the flax cycles. Midfollicular phase testosterone concentrations were slightly higher during flax cycles. Flax seed ingestion had no effect on early follicular phase concentrations of DHEA-S, PRL, or sex hormone-binding globulin. Our data suggest a significant specific role for lignans in the relationship between diet and sex steroid action, and possibly between diet and the risk of breast and other hormonally dependent cancers.",
"title": "Effect of flax seed ingestion on the menstrual cycle."
},
{
"docid": "MED-2973",
"text": "OBJECTIVE: Type 2 diabetes mellitus appears to involve an interaction between susceptible genetic backgrounds and environmental factors including highly calorific diets. As it is important to identify modifiable risk factors that may help reduce the risk of type 2 diabetes mellitus, the aim of the present study was to determine the association between egg consumption and the risk of type 2 diabetes mellitus. DESIGN: A specifically designed questionnaire was used to collect information on possible risk factors of type 2 diabetes mellitus. The odds ratios and 95 % confidence intervals for type 2 diabetes mellitus were calculated by conditional logistic regression. SETTING: A case-control study in a Lithuanian out-patient clinic was performed in 2001. SUBJECTS: A total of 234 cases with a newly confirmed diagnosis of type 2 diabetes mellitus and 468 controls free of the disease. RESULTS: Variables such as BMI, family history of diabetes, cigarette smoking, education, morning exercise and plasma TAG level were retained in multivariate logistic regression models as confounders because their inclusion changed the value of the odds ratio by more than 10 % in any exposure category. After adjustment for possible confounders more than twofold increased risk of type 2 diabetes mellitus was determined for individuals consuming 3-4·9 eggs/week (OR = 2·60; 95 % CI 1·34, 5·08) and threefold increased risk of the disease was determined for individuals consuming ≥5 eggs/week (OR = 3·02; 95 % CI 1·14, 7·98) compared with those eating <1 egg/week. CONCLUSIONS: Our data support a possible relationship of egg consumption and increased risk of type 2 diabetes mellitus.",
"title": "Egg consumption and the risk of type 2 diabetes mellitus: a case-control study."
},
{
"docid": "MED-2975",
"text": "BACKGROUND: Although egg consumption has been associated with elevated plasma levels of cholesterol and triglyceride and with risk of cardiovascular disease in some populations, epidemiologic studies on egg consumption and the risk of diabetes are extremely sparse, particularly in the Chinese population. METHOD: Data from a household survey in the year 2002 among 2849 adults aged ≥20 y from a nationally representative sample in Jiangsu Province, China, were used. Dietary information was assessed by a validated food frequency questionnaire and 3 d weighed food records. Fasting blood specimens were collected. RESULTS: After the adjustment for age, total calorie intake, education, smoking, family history of diabetes, and sedentary activity, egg consumption was significantly and positively associated with diabetes risk, particularly in women. The odds ratios (OR) (95% CI) of diabetes associated with egg consumption <2/wk, 2-6/wk, and ≥1/d in the total sample were 1.00, 1.75, 2.28 (1.14-4.54), respectively (P for trend 0.029). Corresponding ORs (95% CI) in women were 1.00, 1.66, and 3.01 (1.12, 8.12), respectively (P for trend 0.022). Additional adjustment of body mass index attenuated the association, but it remained significant. There was a similar, however, not statistically significant association in men. In addition, plasma triglyceride and total cholesterol levels were significantly higher in women who consumed ≥2 eggs/wk than those who consumed eggs less often. CONCLUSION: Egg consumption was positively associated with the risk of diabetes among the Chinese, particularly in women. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "Egg consumption and the risk of diabetes in adults, Jiangsu, China."
},
{
"docid": "MED-1326",
"text": "BACKGROUND: Because of the rapid change in lifestyle in China, there is concern that diabetes may become epidemic. We conducted a national study from June 2007 through May 2008 to estimate the prevalence of diabetes among Chinese adults. METHODS: A nationally representative sample of 46,239 adults, 20 years of age or older, from 14 provinces and municipalities participated in the study. After an overnight fast, participants underwent an oral glucose-tolerance test, and fasting and 2-hour glucose levels were measured to identify undiagnosed diabetes and prediabetes (i.e., impaired fasting glucose or impaired glucose tolerance). Previously diagnosed diabetes was determined on the basis of self-report. RESULTS: The age-standardized prevalences of total diabetes (which included both previously diagnosed diabetes and previously undiagnosed diabetes) and prediabetes were 9.7% (10.6% among men and 8.8% among women) and 15.5% (16.1% among men and 14.9% among women), respectively, accounting for 92.4 million adults with diabetes (50.2 million men and 42.2 million women) and 148.2 million adults with prediabetes (76.1 million men and 72.1 million women). The prevalence of diabetes increased with increasing age (3.2%, 11.5%, and 20.4% among persons who were 20 to 39, 40 to 59, and > or = 60 years of age, respectively) and with increasing weight (4.5%, 7.6%, 12.8%, and 18.5% among persons with a body-mass index [the weight in kilograms divided by the square of the height in meters] of < 18.5, 18.5 to 24.9, 25.0 to 29.9, and > or = 30.0, respectively). The prevalence of diabetes was higher among urban residents than among rural residents (11.4% vs. 8.2%). The prevalence of isolated impaired glucose tolerance was higher than that of isolated impaired fasting glucose (11.0% vs. 3.2% among men and 10.9% vs. 2.2% among women). CONCLUSIONS: These results indicate that diabetes has become a major public health problem in China and that strategies aimed at the prevention and treatment of diabetes are needed. 2010 Massachusetts Medical Society",
"title": "Prevalence of diabetes among men and women in China."
},
{
"docid": "MED-3834",
"text": "Dietary lignan intakes have been associated with reduced breast cancer risks; however, no previous studies have investigated whether lignan intake might be associated with breast cancer survival. We examined the association of dietary lignan intakes with survival in 1122 women with primary, incident, histologically confirmed breast cancer identified between 1996 and 2001, and with vital status determined through December 31, 2006. Diet in the 12–24 months before diagnosis was assessed with an extensive food frequency questionnaire, and potential confounders assessed from an extensive epidemiologic interview and abstracted clinical data. Lignan intake was calculated using published food composition data. Hazard ratios (HR), and 95% confidence intervals (CIs) for dietary lignan intakes with all cause, and breast cancer mortality were estimated using Cox proportional hazards adjusting for age, education, race, total energy intake, tumor stage, and body mass index. Of the 1122 women with complete dietary data, 160 had died by the end of follow-up. Among postmenopausal women only, those in the highest versus lowest quartile of lignan intakes had a statistically significant reduction in the risk of all cause mortality (HR 0.49, 95% CI 0.26–0.91) and a significantly reduced risk of breast cancer mortality (HR 0.29, 95% CI 0.11–0.76). Higher intakes of dried beans (HR 0.61, 95% CI 0.36–1.03), but not fruits, vegetables, or grains, were also weakly associated with overall mortality. In summary, our results suggest that higher lignan intakes may be associated with improved survival among postmenopausal women with breast cancer.",
"title": "Dietary lignan intakes in relation to survival among women with breast cancer: the Western New York Exposures and Breast Cancer (WEB) Study"
},
{
"docid": "MED-3251",
"text": "CONTEXT: Interferon beta is widely prescribed to treat multiple sclerosis (MS); however, its relationship with disability progression has yet to be established. OBJECTIVE: To investigate the association between interferon beta exposure and disability progression in patients with relapsing-remitting MS. DESIGN, SETTING, AND PATIENTS: Retrospective cohort study based on prospectively collected data (1985-2008) from British Columbia, Canada. Patients with relapsing-remitting MS treated with interferon beta (n = 868) were compared with untreated contemporary (n = 829) and historical (n = 959) cohorts. MAIN OUTCOME MEASURES: The main outcome measure was time from interferon beta treatment eligibility (baseline) to a confirmed and sustained score of 6 (requiring a cane to walk 100 m; confirmed at >150 days with no measurable improvement) on the Expanded Disability Status Scale (EDSS) (range, 0-10, with higher scores indicating higher disability). A multivariable Cox regression model with interferon beta treatment included as a time-varying covariate was used to assess the hazard of disease progression associated with interferon beta treatment. Analyses also included propensity score adjustment to address confounding by indication. RESULTS: The median active follow-up times (first to last EDSS measurement) were as follows: for the interferon beta-treated cohort, 5.1 years (interquartile range [IQR], 3.0-7.0 years); for the contemporary control cohort, 4.0 years (IQR, 2.1-6.4 years); and for the historical control cohort, 10.8 years (IQR, 6.3-14.7 years). The observed outcome rates for reaching a sustained EDSS score of 6 were 10.8%, 5.3%, and 23.1% in the 3 cohorts, respectively. After adjustment for potential baseline confounders (sex, age, disease duration, and EDSS score), exposure to interferon beta was not associated with a statistically significant difference in the hazard of reaching an EDSS score of 6 when either the contemporary control cohort (hazard ratio, 1.30; 95% CI, 0.92-1.83; P = .14) or the historical control cohort (hazard ratio, 0.77; 95% CI, 0.58-1.02; P = .07) were considered. Further adjustment for comorbidities and socioeconomic status, where possible, did not change interpretations, and propensity score adjustment did not substantially change the results. CONCLUSION: Among patients with relapsing-remitting MS, administration of interferon beta was not associated with a reduction in progression of disability.",
"title": "Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis."
},
{
"docid": "MED-3836",
"text": "PURPOSE: Flaxseed, the richest source of mammalian lignan precursors, has previously been shown to reduce the growth of tumors in rats. This study examined, in a randomized double-blind placebo-controlled clinical trial, the effects of dietary flaxseed on tumor biological markers and urinary lignan excretion in postmenopausal patients with newly diagnosed breast cancer. EXPERIMENTAL DESIGN: Patients were randomized to daily intake of either a 25 g flaxseed-containing muffin (n = 19) or a control (placebo) muffin (n = 13). At the time of diagnosis and again at definitive surgery, tumor tissue was analyzed for the rate of tumor cell proliferation (Ki-67 labeling index, primary end point), apoptosis, c-erbB2 expression, and estrogen and progesterone receptor levels. Twenty-four-hour urine samples were analyzed for lignans, and 3-day diet records were evaluated for macronutrient and caloric intake. Mean treatment times were 39 and 32 days in the placebo and flaxseed groups, respectively. RESULTS: Reductions in Ki-67 labeling index (34.2%; P = 0.001) and in c-erbB2 expression (71.0%; P = 0.003) and an increase in apoptosis (30.7%; P = 0.007) were observed in the flaxseed, but not in the placebo group. No significant differences in caloric and macronutrient intake were seen between groups and between pre- and posttreatment periods. A significant increase in mean urinary lignan excretion was observed in the flaxseed group (1,300%; P < 0.01) compared with placebo controls. The total intake of flaxseed was correlated with changes in c-erbB2 score (r = -0.373; P = 0.036) and apoptotic index (r = 0.495; P < 0.004). CONCLUSION: Dietary flaxseed has the potential to reduce tumor growth in patients with breast cancer.",
"title": "Dietary flaxseed alters tumor biological markers in postmenopausal breast cancer."
},
{
"docid": "MED-3845",
"text": "We previously demonstrated that high serum enterolactone levels are associated with a reduced incidence of breast cancer in healthy women. The present study was aimed at investigating whether a similar association might be found between serum enterolactone levels and the mortality of women with early breast cancer. The levels of enterolactone in cryopreserved serum aliquots obtained from 300 patients, operated on for breast cancer, were measured using a time-resolved fluoro-immunoassay. Levels were analyzed in respect to the risk of mortality following surgery. Cox proportional hazard regression models were used to check for prognostic features, to estimate hazard ratios for group comparisons and to test for the interaction on mortality hazards between the variables and enterolactone concentrations. The Fine and Gray competing risk proportional hazard regression model was used to predict the probabilities of breast cancer-related and breast cancer-unrelated mortalities. At a median follow-up time of 23 years (range 0.6-26.1), 180 patients died, 112 of whom died due to breast cancer-related events. An association between a decreased mortality risk and enterolactone levels ≥ 10 nmol/l was found in respect to both all-cause and breast cancer-specific mortality. The difference in mortality hazards was statistically significant, but it appeared to decrease and to lose significance after the first 10 years, though competing risk analysis showed that breast cancer-related mortality risk remained constantly lower in those patients with higher enterolactone levels. Our findings are consistent with those of most recent literature and provide further evidence that mammalian lignans might play an important role in reducing all-cause and cancer-specific mortality of the patients operated on for breast cancer.",
"title": "Serum enterolactone levels and mortality outcome in women with early breast cancer: a retrospective cohort study."
},
{
"docid": "MED-1323",
"text": "Background: Fat and protein sources may influence whether low-carbohydrate diets are associated with type 2 diabetes (T2D). Objective: The objective was to compare the associations of 3 low-carbohydrate diet scores with incident T2D. Design: A prospective cohort study was conducted in participants from the Health Professionals Follow-Up Study who were free of T2D, cardiovascular disease, or cancer at baseline (n = 40,475) for up to 20 y. Cumulative averages of 3 low-carbohydrate diet scores (high total protein and fat, high animal protein and fat, and high vegetable protein and fat) were calculated every 4 y from food-frequency questionnaires and were associated with incident T2D by using Cox models. Results: We documented 2689 cases of T2D during follow-up. After adjustments for age, smoking, physical activity, coffee intake, alcohol intake, family history of T2D, total energy intake, and body mass index, the score for high animal protein and fat was associated with an increased risk of T2D [top compared with bottom quintile; hazard ratio (HR): 1.37; 95% CI: 1.20, 1.58; P for trend < 0.01]. Adjustment for red and processed meat attenuated this association (HR: 1.11; 95% CI: 0.95, 1.30; P for trend = 0.20). A high score for vegetable protein and fat was not significantly associated with the risk of T2D overall but was inversely associated with T2D in men aged <65 y (HR: 0.78; 95% CI: 0.66, 0.92; P for trend = 0.01, P for interaction = 0.01). Conclusions: A score representing a low-carbohydrate diet high in animal protein and fat was positively associated with the risk of T2D in men. Low-carbohydrate diets should obtain protein and fat from foods other than red and processed meat.",
"title": "Low-carbohydrate diet scores and risk of type 2 diabetes in men"
},
{
"docid": "MED-3958",
"text": "Flanders is densely populated with much industry and intensive farming. Sexual maturation of adolescents (aged 14-15 years) was studied in relation to internal exposure to pollutants. Serum levels of pollutants and sex hormones were measured in 1679 participants selected as a random sample of the adolescents residing in the study areas. Data on sexual development were obtained from the medical school examination files. Self-assessment questionnaires provided information on health, use of medication and lifestyle factors. In boys, serum levels of hexachlorobenzene (HCB), p,p'-DDE and polychlorinated biphenyls (sum of marker PCB138, 153 and 180) were significantly and positively associated with pubertal staging (pubic hair and genital development). Higher levels of serum HCB and blood lead were associated with, respectively, a lower and a higher risk of gynecomastia. In girls, significant and negative associations were detected between blood lead and pubic hair development; higher exposure to PCBs was significantly associated with a delay in timing of menarche. Environmental exposures to pollutants at levels actually present in the Flemish population are associated with measurable effects on pubertal development. However, further understanding of toxic mode of action and sensitive windows of exposure is needed to explain the current findings.",
"title": "Internal exposure to pollutants and sexual maturation in Flemish adolescents."
},
{
"docid": "MED-2976",
"text": "Background: Type 2 diabetes (T2D) remains an important public health issue in the United States. There are limited and inconsistent data on the association between egg consumption and fasting glucose or incident diabetes. Objectives: We assessed the association between egg intake and incident diabetes in older adults. Design: In this prospective study of 3898 men and women from the Cardiovascular Health Study (1989–2007), we assessed egg consumption by using a picture-sorted food questionnaire and ascertained incident T2D annually by using information on hypoglycemic agents and plasma glucose. We used Cox proportional hazards models to estimate adjusted relative risks. Results: During a mean follow-up of 11.3 y, 313 new cases of T2D occurred. Crude incidence rates of T2D were 7.39, 6.83, 7.00, 6.72, and 12.20 per 1000 person-years in people who reported egg consumption of never, <1 egg/mo, 1–3 eggs/mo, 1–4 eggs/wk, and almost daily, respectively. In multivariable-adjusted models, there was no association between egg consumption and increased risk of T2D in either sex and overall. In a secondary analysis, dietary cholesterol was not associated with incident diabetes (P for trend = 0.47). In addition, egg consumption was not associated with clinically meaningful differences in fasting glucose, fasting insulin, or measures of insulin resistance despite small absolute analytic differences that were significant. Conclusion: In this cohort of older adults with limited egg intake, there was no association between egg consumption or dietary cholesterol and increased risk of incident T2D.",
"title": "Egg consumption and risk of type 2 diabetes in older adults"
},
{
"docid": "MED-1324",
"text": "Six noninsulin-dependent diabetic subjects received meals containing 25 g carbohydrate either as potato or as spaghetti. The meals were repeated with the addition of 25 g protein and with 25 g protein and 25 g fat. Blood glucose and insulin responses were measured for 4 h after the test meal. When carbohydrate was given alone, the blood glucose and serum insulin increments were higher for the potato meal. The addition of protein increased the insulin responses to both carbohydrates and slightly reduced the glycemic response to mashed potato (F = 2.04, p less than 0.05). The further addition of fat reduced the glycemic response to mashed potato (F = 14.63, p less than 0.001) without any change in the blood glucose response to spaghetti (F = 0.94, NS). The different responses to coingestion of protein and fat reduced the difference between the glycemic responses to the two carbohydrates.",
"title": "Differential effect of protein and fat ingestion on blood glucose responses to high- and low-glycemic-index carbohydrates in noninsulin-dependent d..."
},
{
"docid": "MED-4779",
"text": "ABSTRACT BACKGROUND Tea consumption has been extensively studied in relation to various diseases, several epidemiologic studies have been performed to investigate the association of tea consumption with type 2 diabetes; however, the results of these studies were not entirely consistent. OBJECTIVE To conduct a meta-analysis of studies that assessed the association of tea consumption and the risk of type 2 diabetes. RESEARCH DESIGN AND METHODS We performed a systematic literature search through November 2008 in PUBMED, MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews. The search was limited to English-language studies. Studies were excluded if they were type 1 diabetes, animal studies. Nine cohort studies were identified by two authors, and summary relative risks (RRs) were calculated using a random-effects model. RESULTS We identified nine cohort studies, including 324,141 participants and 11,400 incident cases of type 2 diabetes with follow-up ranging from 5 to 18 years. The summary adjusted RR did not show that tea consumption was associated with a reduced type 2 diabetes risk (RR, 0.96; 95% confidence interval (CI), 0.92–1.01). Evidence from the results of our stratified analyses revealed that tea consumption ≥4 cups per day (RR, 0.8; 95% CI, 0.7–0.93) might play a role in the prevention of type 2 diabetes. However, no statistically significant association was observed for sex and the follow-up durations stratified between tea consumption and type 2 diabetes. CONCLUSIONS This meta-analysis indicates that tea consumption ≥4 cups per day may lower the risk of type 2 diabetes.",
"title": "Tea Consumption and Risk of Type 2 Diabetes: A Meta-Analysis of Cohort Studies"
},
{
"docid": "MED-3247",
"text": "Objective: The chemotherapeutic agent mitoxantrone was approved for use in multiple sclerosis (MS) in 2000. After a review of all the available evidence, the original report of the Therapeutics and Technology Assessment Subcommittee in 2003 concluded that mitoxantrone probably reduced clinical attack rates, MRI activity, and disease progression. Subsequent reports of decreased systolic function, heart failure, and leukemia prompted the US Food and Drug Administration to institute a “black box” warning in 2005. This review was undertaken to examine the available literature on the efficacy and safety of mitoxantrone use in patients with MS since the initial report. Methods: Relevant articles were obtained through a review of the medical literature and the strength of the available evidence was graded according to the American Academy of Neurology evidence classification scheme. Results: The accumulated Class III and IV evidence suggests an increased incidence of systolic dysfunction and therapy-related acute leukemia (TRAL) with mitoxantrone therapy. Systolic dysfunction occurs in ∼12% of patients with MS treated with mitoxantrone, congestive heart failure occurs in ∼0.4%, and leukemia occurs in ∼0.8%. The number needed to harm is 8 for systolic dysfunction and 123 for TRAL. There is no new efficacy evidence that would change the recommendation from the previous report. Conclusions: The risk of systolic dysfunction and leukemia in patients treated with mitoxantrone is higher than suggested at the time of the previous report, although comprehensive postmarketing surveillance data are lacking. GLOSSARY",
"title": "Evidence Report: The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis"
},
{
"docid": "MED-3954",
"text": "BACKGROUND: A male epidemic of ischaemic heart disease (IHD) emerges with economic development. It has previously been hypothesised that this epidemic is due to nutritionally driven levels of pubertal sex steroids, which lead to a more atherogenic body shape and lipid profile in boys but not girls, without any sex-specific effects on glucose metabolism. This study tests this hypothesis by examining the association of childhood meat eating with IHD risk in a developing Chinese population. METHODS: Multivariable linear and censored regression was used in a cross-sectional study of 19,418 Chinese older (≥ 50 years) men and women from the Guangzhou Biobank Cohort Study (phases 2 and 3) to assess the adjusted associations of childhood meat eating with waist to hip ratio (WHR), high-density lipoprotein cholesterol and fasting plasma glucose. RESULTS: Adjusted for age, childhood hunger, life-course socioeconomic position and current lifestyle childhood almost daily meat eating compared with less than weekly meat eating was associated with higher WHR (0.007, 95% CI 0.0003 to 0.01) in men but not women. No association with fasting glucose was observed. CONCLUSIONS: Given the potential limitations of this study, especially the crude nature of the exposure and modest findings, the results should be considered as preliminary. However, they do lend support to the hypothesis that the male epidemic of premature IHD and sexual divergence in IHD rates that occur with economic development may be nutritionally driven in childhood. In elucidating the developmental origins of non-communicable chronic diseases, more attention should be focused on the sociohistorical context and the role of puberty.",
"title": "Does childhood meat eating contribute to sex differences in risk factors for ischaemic heart disease in a developing population?"
},
{
"docid": "MED-3840",
"text": "The incidence of breast cancer is increasing in the Western world and there is an urgent need for studies of the mechanisms of sex steroids in order to develop novel preventive strategies. Diet modifications may be among the means for breast cancer prevention. Angiogenesis, key in tumor progression, is regulated by the balance between pro- and anti-angiogenic factors, which are controlled in the extracellular space. Sampling of these molecules at their bioactive compartment is therefore needed. The aims of this study were to explore if tamoxifen, one of the most used anti-estrogen treatments for breast cancer affected some of the most important endogenous angiogenesis regulators, vascular endothelial growth factor (VEGF), angiogenin, and endostatin in normal breast tissue in vivo and if a diet supplementation with flaxseed had similar effects as tamoxifen in the breast. Microdialysis was used for in situ sampling of extracellular proteins in normal breast tissue of women before and after six weeks of tamoxifen treatment or before and after addition of 25 g/day of ground flaxseed to the diet or in control women. We show significant correlations between estradiol and levels of VEGF, angiogenin, and endostatin in vivo, which was verified in ex vivo breast tissue culture. Moreover, tamoxifen decreased the levels of VEGF and angiogenin in the breast whereas endostatin increased significantly. Flaxseed did not alter VEGF or angiogenin levels but similar to tamoxifen the levels of endostatin increased significantly. We conclude that one of the mechanisms of tamoxifen in normal breast tissue include tipping of the angiogenic balance into an anti-angiogenic state and that flaxseed has limited effects on the pro-angiogenic factors whereas the anti-angiogenic endostatin may be modified by diet. Further studies of diet modifications for breast cancer prevention are warranted.",
"title": "Tamoxifen and Flaxseed Alter Angiogenesis Regulators in Normal Human Breast Tissue In Vivo"
},
{
"docid": "MED-3956",
"text": "Early onset of puberty may confer adverse health consequences. Thus, modifiable factors influencing the timing of puberty are of public health interest. Childhood overweight as a factor in the earlier onset of menarche has been supported by prospective evidence; nonetheless, its overall contribution may have been overemphasized, since secular trends toward a younger age at menarche have not been a universal finding during the recent obesity epidemic. Current observational studies suggest notable associations between dietary intakes and pubertal timing beyond contributions to an energy imbalance: children with the highest intakes of vegetable protein or animal protein experience pubertal onset up to 7 months later or 7 months earlier, respectively. Furthermore, girls with high isoflavone intakes may experience the onset of breast development and peak height velocity approximately 7-8 months later. These effect sizes are on the order of those observed for potentially neuroactive steroid hormones. Thus, dietary patterns characterized by higher intakes of vegetable protein and isoflavones and lower intakes of animal protein may contribute to a lower risk of breast cancer or a lower total mortality. © 2012 International Life Sciences Institute.",
"title": "Beyond overweight: nutrition as an important lifestyle factor influencing timing of puberty."
}
] |
[
{
"docid": "MED-4533",
"text": "CONTEXT: Lead, mercury, and arsenic intoxication have been associated with the use of Ayurvedic herbal medicine product (HMPs). OBJECTIVES: To determine the prevalence and concentration of heavy metals in Ayurvedic HMPs manufactured in South Asia and sold in Boston-area stores and to compare estimated daily metal ingestion with regulatory standards. DESIGN AND SETTING: Systematic search strategy to identify all stores 20 miles or less from Boston City Hall that sold Ayurvedic HMPs from South Asia by searching online Yellow Pages using the categories markets, supermarkets, and convenience stores, and business names containing the word India, Indian cities, and Indian words. An online national directory of Indian grocery stores, a South Asian community business directory, and a newspaper were also searched. We visited each store and purchased all unique Ayurvedic HMPs between April 25 and October 24, 2003. MAIN OUTCOME MEASURES: Concentrations (microg/g) of lead, mercury, and arsenic in each HMP as measured by x-ray fluorescence spectroscopy. Estimates of daily metal ingestion for adults and children estimated using manufacturers' dosage recommendations with comparisons to US Pharmacopeia and US Environmental Protection Agency regulatory standards. RESULTS: A total of 14 (20%) of 70 HMPs (95% confidence interval, 11%-31%) contained heavy metals: lead (n = 13; median concentration, 40 microg/g; range, 5-37,000), mercury (n = 6; median concentration, 20,225 microg/g; range, 28-104,000), and/or arsenic (n = 6; median concentration, 430 microg/g; range, 37-8130). If taken as recommended by the manufacturers, each of these 14 could result in heavy metal intakes above published regulatory standards. CONCLUSIONS: One of 5 Ayurvedic HMPs produced in South Asia and available in Boston South Asian grocery stores contains potentially harmful levels of lead, mercury, and/or arsenic. Users of Ayurvedic medicine may be at risk for heavy metal toxicity, and testing of Ayurvedic HMPs for toxic heavy metals should be mandatory.",
"title": "Heavy metal content of ayurvedic herbal medicine products."
},
{
"docid": "MED-5216",
"text": "Vitamin A deficiency (VAD) has been recognized as a public-health issue in developing countries. Economic constraints, sociocultural limitations, insufficient dietary intake, and poor absorption leading to depleted vitamin A stores in the body have been regarded as potential determinants of the prevalence of VAD in South Asian developing countries. VAD is exacerbated by lack of education, poor sanitation, absence of new legislation and enforcement of existing food laws, and week monitoring and surveillance system. Several recent estimates confirmed higher morbidly and mortality rate among children and pregnant and non-pregnant women of childbearing age. Xerophthalmia is the leading cause of preventable childhood blindness with its earliest manifestations as night blindness and Bitot's spots, followed by blinding keratomalacia, all of which are the ocular manifestations of VAD. Children need additional vitamin A because they do not consume enough in their normal diet. There are three general ways for improving vitamin A status: supplementation, fortification, and dietary diversification. These approaches have not solved the problem in South Asian countries to the desired extent because of poor governmental support and supervision of vitamin A supplementation twice a year. An extensive review of the extant literature was carried out, and the data under various sections were identified by using a computerized bibliographic search via PubMed, Web of Science, and Google Scholar. All abstracts and full-text articles were examined, and the most relevant articles were selected for screening and inclusion in this review. Conclusively, high prevalence of VAD in South Asian developing countries leads to increased morbidity and mortality among infants, children, and pregnant women. Therefore, stern efforts are needed to address this issue of public-health significance at local and international level in lower- and middle-income countries of South Asia.",
"title": "Prevalence of Vitamin A Deficiency in South Asia: Causes, Outcomes, and Possible Remedies"
},
{
"docid": "MED-4783",
"text": "INTRODUCTION: Historically, breast cancer incidence has been substantially higher in the United States than in Asia. When Asian women migrate to the United States, their breast cancer risk increases over several generations and approaches that for U.S. Whites. Thus, modifiable factors, such as diet, may be responsible. METHODS: In this population-based case-control study of breast cancer among women of Chinese, Japanese, and Filipino descent, ages 20 to 55 years, and living in San Francisco-Oakland (California), Los Angeles (California) and Oahu (Hawaii), we interviewed 597 cases (70% of those eligible) and 966 controls (75%) about adolescent and adult diet and cultural practices. For subjects with mothers living in the United States (39% of participants), we interviewed mothers of 99 cases (43% of eligible) and 156 controls (40%) about the daughter's childhood exposures. Seventy-three percent of study participants were premenopausal at diagnosis. RESULTS: Comparing highest with lowest tertiles, the multivariate relative risks (95% confidence interval) for childhood, adolescent, and adult soy intake were 0.40 (0.18-0.83; P(trend) = 0.03), 0.80 (0.59-1.08; P(trend) = 0.12), and 0.76 (0.56-1.02; P(trend) = 0.04), respectively. Inverse associations with childhood intake were noted in all three races, all three study sites, and women born in Asia and the United States. Adjustment for measures of westernization attenuated the associations with adolescent and adult soy intake but did not affect the inverse relationship with childhood soy intake. DISCUSSION: Soy intake during childhood, adolescence, and adult life was associated with decreased breast cancer risk, with the strongest, most consistent effect for childhood intake. Soy may be a hormonally related, early-life exposure that influences breast cancer incidence.",
"title": "Childhood soy intake and breast cancer risk in Asian American women."
},
{
"docid": "MED-5002",
"text": "BACKGROUND/AIMS: Cell culture studies suggest that phytoestrogens, abundant in soy products such as tempe and tofu, could protect against cognitive decline. Paradoxically, the Honolulu Asia Aging Study reported an increased risk for cognitive impairment and other dementia markers with high tofu (soybean curd) intake. METHODS: A cross-sectional study was carried out in 2 rural sites (Borobudur and Sumedang) and 1 urban site (Jakarta) among mainly Javanese and Sundanese elderly (n = 719, 52-98 years of age). Memory was measured using a word learning test sensitive to dementia and soy consumption was assessed using Food Frequency Questionnaire items. RESULTS: High tofu consumption was associated with worse memory (beta = -0.18, p < 0.01, 95% CI = -0.34 to -0.06), while high tempe consumption (a fermented whole soybean product) was independently related to better memory (beta = 0.12, p < 0.05, 95% CI = 0.00-0.28), particularly in participants over 68 years of age. Fruit consumption also had an independent positive association. The analyses were controlled for age, sex, education, site and intake of other foods. CONCLUSION: The results for tofu consumption as a risk factor for low memory function may tie in with the Honolulu Asia Aging Study data. It is unclear whether these negative associations could be attributed to potential toxins or to its phytoestrogen levels. Estrogen (through which receptors phytoestrogens can exert effects) was found to increase dementia risk in women over 65 years of age. Tempe contains high levels of phytoestrogens, but (due to fermentation) also exhibits high folate levels which may exert protective effects. Future studies should validate these findings and investigate potential mechanisms. Copyright 2008 S. Karger AG, Basel.",
"title": "High tofu intake is associated with worse memory in elderly Indonesian men and women."
},
{
"docid": "MED-1717",
"text": "BACKGROUND: Excess bodyweight, expressed as increased body-mass index (BMI), is associated with the risk of some common adult cancers. We did a systematic review and meta-analysis to assess the strength of associations between BMI and different sites of cancer and to investigate differences in these associations between sex and ethnic groups. METHODS: We did electronic searches on Medline and Embase (1966 to November 2007), and searched reports to identify prospective studies of incident cases of 20 cancer types. We did random-effects meta-analyses and meta-regressions of study-specific incremental estimates to determine the risk of cancer associated with a 5 kg/m2 increase in BMI. FINDINGS: We analysed 221 datasets (141 articles), including 282,137 incident cases. In men, a 5 kg/m2 increase in BMI was strongly associated with oesophageal adenocarcinoma (RR 1.52, p<0.0001) and with thyroid (1.33, p=0.02), colon (1.24, p<0.0001), and renal (1.24, p <0.0001) cancers. In women, we recorded strong associations between a 5 kg/m2 increase in BMI and endometrial (1.59, p<0.0001), gallbladder (1.59, p=0.04), oesophageal adenocarcinoma (1.51, p<0.0001), and renal (1.34, p<0.0001) cancers. We noted weaker positive associations (RR <1.20) between increased BMI and rectal cancer and malignant melanoma in men; postmenopausal breast, pancreatic, thyroid, and colon cancers in women; and leukaemia, multiple myeloma, and non-Hodgkin lymphoma in both sexes. Associations were stronger in men than in women for colon (p<0.0001) cancer. Associations were generally similar in studies from North America, Europe and Australia, and the Asia-Pacific region, but we recorded stronger associations in Asia-Pacific populations between increased BMI and premenopausal (p=0.009) and postmenopausal (p=0.06) breast cancers. INTERPRETATION: Increased BMI is associated with increased risk of common and less common malignancies. For some cancer types, associations differ between sexes and populations of different ethnic origins. These epidemiological observations should inform the exploration of biological mechanisms that link obesity with cancer.",
"title": "Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies."
},
{
"docid": "MED-5022",
"text": "The tropical mangosteen fruit has long been prized in Southeast Asia for its traditional healing properties. Mangosteen fruit juice is now available in the United States and marketed for its purported health benefits. We describe a case of severe lactic acidosis associated with the use of mangosteen juice as a dietary supplement.",
"title": "Severe lactic acidosis associated with juice of the mangosteen fruit Garcinia mangostana."
},
{
"docid": "MED-5340",
"text": "In Asia, vegetarianism is a well-established eating behavior. It appears that the adoption of a vegan diet leads to a lessening of several health risk factors. Although vegetarianism has some notable effects on the hematological system, the effect on the nephrological system has not been well clarified. The pattern of renal function parameters was studied in 25 Thai vegans compared with 25 non-vegetarians. Of the studied parameters, it was found that urine protein was significantly different (p < 0.05) in vegans and controls. Vegans had significantly lower urine protein level.",
"title": "Renal function parameters of Thai vegans compared with non-vegans."
},
{
"docid": "MED-4026",
"text": "AIM: The aim of this study was to investigate possible risk factors for dental caries in primary school children. METHODS: Children aged 10-12 years (n = 257) residing in Lithgow, a non-fluoridated community in New South Wales, Australia, were examined for caries experience in the permanent dentition. Information on dental practices, diet, residential movements, and socioeconomic status were obtained from self-completed questionnaires. RESULTS: Caries risk in the permanent teeth was associated with social disadvantage and diet. Among the dietary factors, the frequency of fruit consumption was associated with higher odds of caries experience (odds ratio: 1.52, 95% confidence intervals: 1.05, 2.21). CONCLUSIONS: Exposure to a high level of fruit consumption was suggestive of increased caries risk. Longitudinal studies are required to investigate the relationship between fruit consumption and dental caries. © 2011 Blackwell Publishing Asia Pty Ltd.",
"title": "Is the consumption of fruit cariogenic?"
},
{
"docid": "MED-4963",
"text": "Because of the worldwide popularization of Japanese cuisine, the traditional Japanese fish dishes sushi and sashimi that are served in Japanese restaurants and sushi bars have been suspected of causing fishborne parasitic zoonoses, especially anisakiasis. In addition, an array of freshwater and brackish-water fish and wild animal meats, which are important sources of infection with zoonotic parasites, are served as sushi and sashimi in rural areas of Japan. Such fishborne and foodborne parasitic zoonoses are also endemic in many Asian countries that have related traditional cooking styles. Despite the recent increase in the number of travelers to areas where these zoonoses are endemic, travelers and even infectious disease specialists are unaware of the risk of infection associated with eating exotic ethnic dishes. The aim of this review is to provide practical background information regarding representative fishborne and foodborne parasitic zoonoses endemic in Asian countries.",
"title": "Sushi delights and parasites: the risk of fishborne and foodborne parasitic zoonoses in Asia."
},
{
"docid": "MED-5293",
"text": "Summary Background Quantification of the disease burden caused by different risks informs prevention by providing an account of health loss different to that provided by a disease-by-disease analysis. No complete revision of global disease burden caused by risk factors has been done since a comparative risk assessment in 2000, and no previous analysis has assessed changes in burden attributable to risk factors over time. Methods We estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010. We estimated exposure distributions for each year, region, sex, and age group, and relative risks per unit of exposure by systematically reviewing and synthesising published and unpublished data. We used these estimates, together with estimates of cause-specific deaths and DALYs from the Global Burden of Disease Study 2010, to calculate the burden attributable to each risk factor exposure compared with the theoretical-minimum-risk exposure. We incorporated uncertainty in disease burden, relative risks, and exposures into our estimates of attributable burden. Findings In 2010, the three leading risk factors for global disease burden were high blood pressure (7·0% [95% uncertainty interval 6·2–7·7] of global DALYs), tobacco smoking including second-hand smoke (6·3% [5·5–7·0]), and alcohol use (5·5% [5·0–5·9]). In 1990, the leading risks were childhood underweight (7·9% [6·8–9·4]), household air pollution from solid fuels (HAP; 7·0% [5·6–8·3]), and tobacco smoking including second-hand smoke (6·1% [5·4–6·8]). Dietary risk factors and physical inactivity collectively accounted for 10·0% (95% UI 9·2–10·8) of global DALYs in 2010, with the most prominent dietary risks being diets low in fruits and those high in sodium. Several risks that primarily affect childhood communicable diseases, including unimproved water and sanitation and childhood micronutrient deficiencies, fell in rank between 1990 and 2010, with unimproved water we and sanitation accounting for 0·9% (0·4–1·6) of global DALYs in 2010. However, in most of sub-Saharan Africa childhood underweight, HAP, and non-exclusive and discontinued breastfeeding were the leading risks in 2010, while HAP was the leading risk in south Asia. The leading risk factor in Eastern Europe, most of Latin America, and southern sub-Saharan Africa in 2010 was alcohol use; in most of Asia, North Africa and Middle East, and central Europe it was high blood pressure. Despite declines, tobacco smoking including second-hand smoke remained the leading risk in high-income north America and western Europe. High body-mass index has increased globally and it is the leading risk in Australasia and southern Latin America, and also ranks high in other high-income regions, North Africa and Middle East, and Oceania. Interpretation Worldwide, the contribution of different risk factors to disease burden has changed substantially, with a shift away from risks for communicable diseases in children towards those for non-communicable diseases in adults. These changes are related to the ageing population, decreased mortality among children younger than 5 years, changes in cause-of-death composition, and changes in risk factor exposures. New evidence has led to changes in the magnitude of key risks including unimproved water and sanitation, vitamin A and zinc deficiencies, and ambient particulate matter pollution. The extent to which the epidemiological shift has occurred and what the leading risks currently are varies greatly across regions. In much of sub-Saharan Africa, the leading risks are still those associated with poverty and those that affect children. Funding Bill & Melinda Gates Foundation.",
"title": "A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010"
},
{
"docid": "MED-1047",
"text": "Fundamental studies of the laxative action of wheat bran were undertaken in the United States in the early decades of the 20th century. Walker in South Africa extended these studies among African blacks and later suggested that cereal fiber protected them against certain metabolic disorders. Trowell in Uganda elaborated this concept with regard to the rarity of common noninfective diseases of the colon. Another stream of inquiry stemmed from the hypothesis of Cleave who postulated that the presence of refined sugar, and to a lesser extent white flour, caused many metabolic diseases, while the loss of fiber caused certain colonic disorders. Meanwhile Burkitt had collected massive evidence of the rarity of appendicitis and many venous disorders in rural Africa and parts of Asia. In 1972 Trowell proposed a new physiological definition of fiber in terms of the residue of plant foods that resisted digestion by alimentary enzymes of man. Southgate has proposed chemical methods to analyze the components of dietary fiber: cellulose, hemicellulose, and lignin.",
"title": "The development of the concept of dietary fiber in human nutrition."
},
{
"docid": "MED-1056",
"text": "Decades ago discussion of an impending global pandemic of obesity was thought of as heresy. Diets in the 1970’s began to shift toward increased reliance upon processed foods, increased away from home intake and greater use of edible oils and sugar-sweetened beverages. Reduced physical activity and increased sedentary time was seen also. These changes began in the early 1990-‘s in the low and middle income world but did not become clearly recognized until diabetes, hypertension and obesity began to dominate the globe. Urban and rural areas from sub-Saharan Africa and South Asia’s poorest countries to the higher income ones are shown to have experienced rapid increases in overweight and obesity status. Concurrent rapid shifts in diet and activity are documented. An array of large-scale programmatic and policy shifts are being explored in a few countries; however despite the major health challenges faced, few countries are serious in addressing prevention of the dietary challenges faced.",
"title": "NOW AND THEN: The Global Nutrition Transition: The Pandemic of Obesity in Developing Countries"
},
{
"docid": "MED-3484",
"text": "The objective of this work is to review data from epidemiological and preclinical studies addressing the potential benefits of diets based on flavonoids for cancer prevention. Flavonoids are subdivided into subclasses including flavonols, flavones, flavanones, flavan-3-ols, anthocyanidins, and isoflavones. Epidemiological studies suggest dietary intake of flavonoids may reduce the risk of tumors of the breast, colon, lung, prostate, and pancreas. However, some studies have reported inconclusive or even harmful associations. A major challenge in the interpretation of epidemiological studies is that most of the data originate from case-control studies and retrospective acquisition of flavonoid intake. Differences in agricultural, sociodemographics, and lifestyle factors contribute to the heterogeneity in the intake of flavonoids among populations residing in the United States, Europe, and Asia. Dose and timing of exposure may influence the anticancer response to flavonoid-rich diets. A limited number of intervention trials of flavonoids have documented cancer preventative effects. Proposed anticancer mechanisms for flavonoids are inhibition of proliferation, inflammation, invasion, metastasis, and activation of apoptosis. Prospective studies with larger sample sizes are needed to develop biomarkers of flavonoid intake and effect. Mechanistic studies are needed to ascertain how flavonoid-rich diets influence gene regulation for cancer prevention.",
"title": "Flavonoids and cancer prevention: a review of the evidence."
},
{
"docid": "MED-4358",
"text": "Summary Since their discovery almost a century ago, bacterial viruses (bacteriophages or ‘phages’) have been used to prevent and treat a multitude of bacterial infections (phage therapy: PT). In addition, they have been the basis for many advances in genetics and biochemistry. Phage therapy was performed on human subjects in the United States, Europe and Asia in the few decades following their discovery. However, Western countries largely abandoned PT in favour of antibiotics in the 1940s. The relatively recent renaissance of PT in the West can be attributed partly to the increasing prevalence of antibiotic resistance in human and animal pathogens. However, the stringent controls on human trials now required in the United States and Europe have led to a greater number of domestic animal and agricultural applications as an alternative to PT in man. This trend is set to continue, at least in the short term, with recent approval from the Food and Drug Administration allowing commercial phage treatments to be used in human food in the USA. Nevertheless, despite these significant milestones and the growing number of successful PT trials, significant obstacles remain to their widespread use in animals, food and ultimately medicine in many parts of the world. This review will provide a brief overview of the history of PT in the West and will summarize some of the key findings of phage biocontrol studies in animals and meat products.",
"title": "Bacteriophage biocontrol in animals and meat products"
},
{
"docid": "MED-4660",
"text": "Dietary seaweeds, common in Asia and in Asian restaurants, have become established as part of popular international cuisine. To understand the possibility for iodine-induced thyroid dysfunction better, we collected samples of the most common dietary seaweeds available from commercial sources in the United States, as well as harvester-provided samples from Canada, Tasmania, and Namibia. Altogether, 12 different species of seaweeds were analyzed for iodine content, and found to range from 16 microg/g (+/-2) in nori (Porphyra tenera) to over 8165 +/- 373 microg/g in one sample of processed kelp granules (a salt substitute) made from Laminaria digitata. We explored variation in preharvest conditions in a small study of two Namibian kelps (Laminaria pallida and Ecklonia maxima), and found that iodine content was lowest in sun-bleached blades (514 +/- 42 microg/g), and highest amount in freshly cut juvenile blades (6571 +/- 715 microg/g). Iodine is water-soluble in cooking and may vaporize in humid storage conditions, making average iodine content of prepared foods difficult to estimate. It is possible some Asian seaweed dishes may exceed the tolerable upper iodine intake level of 1100 microg/d.",
"title": "Variability of iodine content in common commercially available edible seaweeds."
},
{
"docid": "MED-4095",
"text": "Statistics compiled by the National Cancer Institute indicate that, between 1935 and 1974, age-adjusted mortality from most 'Western' cancers (those of the breast, colon, prostate, pancreas, ovary, and kidney) rose dramatically in African-Americans. This phenomenon is paralleled by marked increases in the incidence of these cancers in Asia and Southern Europe during the latter 20th century, in conjunction with increased intakes of dietary animal products. A credible case can be made that diets rich in animal products work in various complementary ways to up-regulate serum levels of insulin, free IGF-I, and free sex hormones: hormones that appear to have important promotional activity for Western cancers. It seems likely that dietary animal product intake by black Americans increased substantially during the 20th century, and that this fact is primarily responsible for their concurrent marked increase in mortality from Western cancers. A whole-food vegan diet rich in fruits and vegetables, especially if coupled with regular exercise and smoking avoidance, could be expected to have a remarkably positive impact on African-American cancer risk, reversing the increases in cancer risk incurred during the 20th century. Copyright 2001 Harcourt Publishers Ltd.",
"title": "Mortality from Western cancers rose dramatically among African-Americans during the 20th century: are dietary animal products to blame?"
},
{
"docid": "MED-5296",
"text": "OBJECTIVE: To study the distribution and interrelationship among constitutional and biochemical variables with blood pressure (BP) in an population of Yanomami indians. To compare these findings with those of other populations. METHODS: The Yanomami indians were part of the INTERSALT, a study comprising 10,079 males and females, aged from 20 to 59 years, belonging to 52 populations in 32 countries in Africa, the Americas, Asia, and Europe. Each of the 52 centers was required to accrue 200 individuals, 25 participants in each age group. The variables analyzed were as follows: age, sex, arterial BP, urinary sodium and potassium excretion (24-hour urine), body mass index, and alcohol ingestion. RESULTS: The findings in the Yanomami population were as follows: a very low urinary sodium excretion (0.9 mmol/24 h); mean systolic and diastolic BP levels of 95.4 mmHg and 61.4 mmHg, respectively; no cases of hypertension or obesity; and they have no knowledge of alcoholic beverages. Their BP levels do not elevate with age. The urinary sodium excretion relates positively and the urinary potassium excretion relates negatively to systolic BP. This correlation was maintained even when controlled for age and body mass index. CONCLUSION: A positive relation between salt intake and blood pressure was detected in the analysis of a set of diverse populations participating in the INTERSALT Study, including populations such as the Yanomami Indians. The qualitative observation of their lifestyle provided additional information.",
"title": "The Yanomami Indians in the INTERSALT Study."
},
{
"docid": "MED-2394",
"text": "Background One of the outcomes positively associated with dioxin exposure in humans is type 2 diabetes. Objectives This study was conducted in order to find the molecular biological evidence for the diabetogenic action of dioxin in adipose samples from Vietnam veterans. Methods We obtained 313 adipose tissue samples both from Vietnam veterans who were exposed to dioxin (Operation Ranch Hand) and from comparison veterans who served in Southeast Asia with no record of dioxin exposure. We conducted quantitative reverse-transcribed polymerase chain reaction studies on selected marker mRNAs from these samples. Results We found the most sensitive and reliable molecular indicator of dioxin-induced diabetes to be the ratio of mRNA of glucose transporter 4 (GLUT4) and nuclear transcription factor kappa B (NFκB), a marker of inflammation. This ratio showed significant correlations to serum dioxin residues and to fasting glucose among those in the Ranch Hand group and, surprisingly, even in the comparison group, who have low levels of dioxin comparable to the general public. Such a correlation in the comparison group was particularly significant among those with known risk factors such as obesity and family history of diabetes. Conclusions These results show that the GLUT4:NFκB ratio is a reliable marker for the diabetogenic action of dioxin, particularly at very low exposure levels that are not much higher than those found in the general public, implying a need to address current exposure levels.",
"title": "Molecular Epidemiologic Evidence for Diabetogenic Effects of Dioxin Exposure in U.S. Air Force Veterans of the Vietnam War"
},
{
"docid": "MED-4050",
"text": "Green tea is a commonly consumed beverage in Asia and has been suggested to have anti-inflammatory and possible anti-carcinogenic properties in laboratory studies. We sought to examine the association between green tea consumption and risk of breast cancer incidence or recurrence, using all available epidemiologic evidence to date. We conducted a systematic search of five databases and performed a meta-analysis of studies of breast cancer risk and recurrence published between 1998 and 2009, encompassing 5,617 cases of breast cancer. Summary relative risks (RR) were calculated using a fixed effects model, and tests of heterogeneity across combined studies were conducted. We identified two studies of breast cancer recurrence and seven studies of breast cancer incidence. Increased green tea consumption (more than three cups a day) was inversely associated with breast cancer recurrence (Pooled RR = 0.73, 95% CI: 0.56-0.96). An analysis of case-control studies of breast cancer incidence suggested an inverse association with a pooled RR of 0.81 (95% CI: 0.75, 0.88) while no association was found among cohort studies of breast cancer incidence. Combining all studies of breast cancer incidence resulted in significant heterogeneity. Available epidemiologic evidence supports the hypothesis that increased green tea consumption may be inversely associated with risk of breast cancer recurrence. The association between green tea consumption and breast cancer incidence remains unclear based on the current evidence.",
"title": "Green tea consumption and breast cancer risk or recurrence: a meta-analysis."
},
{
"docid": "MED-4934",
"text": "Concentrations of polybrominated diphenyl ethers (PBDEs), pesticides, polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons were measured in 136 fish from 14 remote lakes in 8 western US National Parks/Preserves between 2003 and 2005 and compared to human and wildlife contaminant health thresholds. A sensitive (median detection limit −18 pg/g wet weight), efficient (61% recovery at 8 ng/g), reproducible (4.1 %RSD), and accurate (7 % deviation from SRM) analytical method was developed and validated for these analyses. Concentrations of PCBs, hexachlorobenzene, hexachlorocyclohexanes, DDTs and chlordanes in western US fish were comparable to or lower than mountain fish recently collected from Europe, Canada, and Asia. Dieldrin and PBDE concentrations were higher than recent measurements in mountain fish and Pacific Ocean salmon. Concentrations of most contaminants in western US fish were 1–6 orders of magnitude below calculated recreational fishing contaminant health thresholds. However, contaminant concentrations exceeded subsistence fishing cancer screening values in 8 of 14 lakes. Average contaminant concentrations in fish exceeded wildlife contaminant health thresholds for piscivorous mammals in 5 lakes, and piscivorous birds in all 14 lakes. These results indicate that atmospherically deposited organic contaminants can accumulate in high elevation fish, reaching concentrations relevant to human and wildlife health.",
"title": "Atmospherically Deposited PBDEs, Pesticides, PCBs, and PAHs in Western US National Park Fish: Concentrations and Consumption Guidelines"
},
{
"docid": "MED-4101",
"text": "The metabolic syndrome is a common complex entity that has emerged as a worldwide epidemic and major public health care concern with a prevalence of approximately 25% in the United States. There have been a number of different definitions of the metabolic syndrome but all center around the metabolic abnormalities of central obesity, hypertension, decreased high-density lipoproteins and elevated triglycerides with insulin resistance as the uniting physiologic factor. The importance of the metabolic syndrome is not just related to its high prevalence rate but also because it predicts the development of diabetes and cardiovascular disease. Nonalcoholic fatty liver disease is now recognized to be the hepatic component of the metabolic syndrome, which along with its individual components - particularly diabetes and elevated triglycerides, are the major risk factors for the development of nonalcoholic steatohepatitis (NASH); the most severe form of nonalcoholic fatty liver disease. NASH may progress to cirrhosis, hepatocellular carcinoma, and liver failure. It is currently the third most common cause for liver transplantation and is projected to be the leading cause for liver transplantation in 2020. Weight loss (via diet or bariatric surgery) and vitamin E have recently been demonstrated to be effective treatments of NASH. Although these and other agents may prove to be effective treatments for NASH, the most effective therapeutic strategy would be early screening and intervention to prevent the development of insulin resistance and oxidative stress at a societal level. © 2011 The Author. Journal of Digestive Diseases © 2011 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd.",
"title": "Epidemiology of the metabolic syndrome in the USA."
},
{
"docid": "MED-2888",
"text": "Age-related macular degeneration (AMD) is a common disorder that causes irreversible loss of central vision. Increased intake of foods containing zeaxanthin may be effective in preventing AMD because the macula accumulates zeaxanthin and lutein, oxygenated carotenoids with antioxidant and blue light-absorbing properties. Lycium barbarum L. is a small red berry known as Fructus lycii and wolfberry in the West, and Kei Tze and Gou Qi Zi in Asia. Wolfberry is rich in zeaxanthin dipalmitate, and is valued in Chinese culture for being good for vision. The aim of this study, which was a single-blinded, placebo-controlled, human intervention trial of parallel design, was to provide data on how fasting plasma zeaxanthin concentration changes as a result of dietary supplementation with whole wolfberries. Fasting blood was collected from healthy, consenting subjects; fourteen subjects took 15 g/d wolfberry (estimated to contain almost 3 mg zeaxanthin) for 28 d. Repeat fasting blood was collected on day 29. Age- and sex-matched controls (n 13) took no wolfberry. Responses in the two groups were compared using the Mann-Whitney test. After supplementation, plasma zeaxanthin increased 2.5-fold: mean values on day 1 and 29 were 0.038 (sem 0.003) and 0.096 (sem 0.009) micromol/l (P<0.01), respectively, for the supplementation group; and 0.038 (sem 0.003) and 0.043 (sem 0.003) micromol/l (P>0.05), respectively, for the control group. This human supplementation trial shows that zeaxanthin in whole wolfberries is bioavailable and that intake of a modest daily amount markedly increases fasting plasma zeaxanthin levels. These new data will support further study of dietary strategies to maintain macular pigment density.",
"title": "Fasting plasma zeaxanthin response to Fructus barbarum L. (wolfberry; Kei Tze) in a food-based human supplementation trial."
},
{
"docid": "MED-4712",
"text": "Since the beginning of this century, Goji berries and juice are being sold as health food products in western countries and praised in advertisements and in the media for well-being and as an anti-aging remedy. The popularity of Goji products has rapidly grown over the last years thanks to efficient marketing strategies. Goji is a relatively new name given to Lycium barbarum and L. chinense, two close species with a long tradition of use as medicinal and food plants in East Asia, in particular in China. While only L. barbarum is officinal, the fruit (fructus Lycii) and the root bark (cortex Lycii radicis) of both species are used in the folk medicine. We review here the constituents, pharmacology, safety, and uses of L. barbarum and L. chinense with consideration to the different parts of the plant. Investigations of the fruit have focused on proteoglycans, known as \" Lycium barbarum polysaccharides\", which showed antioxidative properties and some interesting pharmacological activities in the context of age related diseases such as atherosclerosis and diabetes. As to the root bark, several compounds have demonstrated a hepatoprotective action as well as inhibitory effects on the rennin/angiotensin system which may support the traditional use for the treatment of hypertension. While there are no signs of toxicity of this plant, two cases of possible interaction with warfarin point to a potential risk of drug interaction. In view of the available pharmacological data and the long tradition of use in the traditional Chinese medicine, L. barbarum and L. chinense certainly deserve further investigation. However, clinical evidences and rigorous procedures for quality control are indispensable before any recommendation of use can be made for Goji products. Copyright Georg Thieme Verlag KG Stuttgart . New York.",
"title": "Goji (Lycium barbarum and L. chinense): Phytochemistry, pharmacology and safety in the perspective of traditional uses and recent popularity."
},
{
"docid": "MED-5117",
"text": "PURPOSE: Because they have large variations in consumption, Asian countries are suitable settings for studies of the effect of relatively high-dose isoflavone intake on breast cancer risk. Nevertheless, no prospective study from Asia has assessed blood or urine levels as biomarkers of isoflavone intake. PATIENTS AND METHODS: A total of 24,226 women ages 40 to 69 years in the Japan Public Health Center-based prospective study who responded to the baseline questionnaire and provided blood in 1990 to 1995 were observed to December 2002. During a mean 10.6 years of follow-up, 144 patients newly diagnosed with breast cancer were identified. Two matched controls for each patient were selected from the cohort. Isoflavone levels were assessed by plasma level and food frequency questionnaire, and the odds ratio of breast cancer according to isoflavone level was estimated using a conditional logistic regression model. RESULTS: We found a statistically significant inverse association between plasma genistein and risk of breast cancer, but no association for plasma daidzein. Adjusted odds ratios for the highest versus lowest quartile of plasma level were 0.34 for genistein (95% CI, 0.16 to 0.74; P for trend, .02) and 0.71 for daidzein (95% CI, 0.35 to 1.44; P for trend, .54). Median plasma genistein values in the control group were 31.9 ng/mL for the lowest and 353.9 ng/mL for the highest quartile groups. Regarding dietary intake of isoflavones, nonsignificant inverse associations were observed for both genistein and daidzein. CONCLUSION: This nested case-control study found an inverse association between plasma genistein and the risk of breast cancer in Japan.",
"title": "Plasma isoflavone level and subsequent risk of breast cancer among Japanese women: a nested case-control study from the Japan Public Health Center-..."
},
{
"docid": "MED-3031",
"text": "Background: Mercury (Hg) is a toxic metal that presents public health risks through fish consumption. A major source of uncertainty in evaluating harmful exposure is inadequate knowledge of Hg concentrations in commercially important seafood. Objectives: We examined patterns, variability, and knowledge gaps of Hg in common commercial seafood items in the United States and compared seafood Hg concentrations from our database to those used for exposure estimates and consumption advice. Methods: We developed a database of Hg concentrations in fish and shellfish common to the U.S. market by aggregating available data from government monitoring programs and the scientific literature. We calculated a grand mean for individual seafood items, based on reported means from individual studies, weighted by sample size. We also compared database results to those of federal programs and human health criteria [U.S. Food and Drug Administration Hg Monitoring Program (FDA-MP), U.S. Environmental Protection Agency (EPA)]. Results: Mean Hg concentrations for each seafood item were highly variable among studies, spanning 0.3–2.4 orders of magnitude. Farmed fish generally had lower grand mean Hg concentrations than their wild counterparts, with wild seafood having 2- to12-fold higher concentrations, depending on the seafood item. However, farmed fish are relatively understudied, as are specific seafood items and seafood imports from Asia and South America. Finally, we found large discrepancies between mean Hg concentrations estimated from our database and FDA-MP estimates for most seafood items examined. Conclusions: The high variability in Hg in common seafood items has considerable ramifications for public health and the formulation of consumption guidelines. Exposure and risk analyses derived from smaller data sets do not reflect our collective, available information on seafood Hg concentrations.",
"title": "A Quantitative Synthesis of Mercury in Commercial Seafood and Implications for Exposure in the United States"
},
{
"docid": "MED-2581",
"text": "A hospital-based case-control study of diet and colorectal cancer was conducted among Chinese in Singapore (who constitute 77% of the population). A total of 203 cases and 425 controls were included. A history of the usual dietary intake one year prior to interview was taken using a quantitative food frequency questionnaire. Daily intakes of nutrients and selected food items were computed and stratified by tertiles of the control range, to assess risk in low-, medium- and high-intake categories. Effects were adjusted in analysis for age, sex, Chinese dialect group and occupation. For cancers of colon and rectum combined, significant observations were a protective effect of high cruciferous vegetable intake (OR = 0.50, p less than 0.01) and a predisposing effect of a high meat/vegetable consumption ratio (OR = 1.77, p less than 0.05). Similar results were observed for colon cancer alone. For rectal cancer alone (only 71 cases), significant (p less than 0.05) protective effects were observed for high intakes of protein (OR = 0.61), fibre (OR = 0.46), beta-carotene (OR = 0.54), cruciferous vegetables (OR = 0.51) and total vegetables (OR = 0.51). When further assessed by multiple logistic regression, tests for trend and assessment of risk in the extreme highest and lowest quintiles of the control range, the factors consistently significant were cruciferous vegetable intake and the meat/vegetable ratio. A particularly high relative risk was also noted in association with low coffee consumption (OR = 1.59, with p less than 0.05 for trend). No consistent trends were noted for fat or fibre intakes. For non-dietary variables investigated, a history of cholecystectomy increased the risk of both cancers combined (OR = 3.43, p less than 0.05) and colon cancer alone (OR = 4.39, p less than 0.01). This study in an Asian population of countries of Southern and Eastern Asia newly undergoing industrialization and in which rapid economic change is reflected in changing cancer patterns, suggests that the protective effects of certain dietary constituents, notably the cruciferous vegetables, may be more important than the hitherto stressed carcinogenic potential of fat and protein.",
"title": "Colorectal cancer and diet in an Asian population--a case-control study among Singapore Chinese."
},
{
"docid": "MED-3876",
"text": "BACKGROUND: Chinese men have lower incidences of prostate cancer compared to men from Europe and North America. Asians consume large quantities of soya, a rich source of isoflavanoids phyto-oestrogens and have high plasma and urinary levels of these compounds. The mammalian lignans, enterolactone and enterodiol, are another group of weak plant oestrogens and are derived from seeds, cereals and grains. Vegetarians have high plasma and urinary concentrations of lignans. METHODS: The concentrations lignans and isoflavonic phyto-oestrogens were determined by gas chromatography-mass spectrometry (GC-MS) in plasma and prostatic fluid from Portuguese, Chinese and British men consuming their traditional diets. RESULTS: In prostatic fluid the mean concentrations of enterolactone were 31, 162 and 20.3 ng/ml for Hong Kong, Portugal and Britain respectively. Very high levels of enterolactone (> 600 ng/ml) were observed in the prostatic fluid of some of the men from Portugal. High concentrations of equol (3270 ng/ml) and daidzein (532 ng/ml) were found in a sample of prostatic fluid from Hong Kong. Higher mean levels of daidzein were observed in prostatic fluid from Hong Kong at 70 ng/ml, compared to 4.6 and 11.3 ng/ml in samples from Portugal and Britain respectively. Mean levels of daidzein were higher in the plasma samples from Hong Kong (31.3 ng/ml) compared to those from Portugal (1.3 ng/ml) and Britain (8.2 ng/ml). In general, the mean plasma concentrations of enterolactone from the three centres were similar, at 6.2, 3.9 and 3.9 ng/ml in samples from Hong Kong Portugal and Britain respectively. CONCLUSIONS: Higher concentrations of the isoflavanoid phyto-oestrogens, daidzein and equol, were found in the plasma and prostatic fluid of men from Hong Kong compared to those from Britain and Portugal. However, the levels of the lignan, enterolactone, were very much higher in prostatic fluid of Portuguese men. Isoflavanoids and lignans have many interesting properties and may, in part, be responsible for lower incidences of prostate cancer in men from Asia and also some Mediterranean countries. The isoflavanoids from soya, which are present in high concentrations in the prostatic fluid of Asian men, may be protective against prostate disease.",
"title": "Lignans and isoflavonoids in plasma and prostatic fluid in men: samples from Portugal, Hong Kong, and the United Kingdom."
},
{
"docid": "MED-2411",
"text": "The relationship between omega-3 polyunsaturated fatty acids (n-3 PUFA) from seafood (eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA) or plant (alpha-linolenic acid, ALA) sources and risk of type 2 diabetes mellitus (DM) remains unclear. We systematically searched multiple literature databases through June 2011 to identify prospective studies examining relations of dietary n-3 PUFA, dietary fish and/or seafood, and circulating n-3 PUFA biomarkers with incidence of DM. Data were independently extracted in duplicate by 2 investigators, including multivariate-adjusted relative risk (RR) estimates and corresponding 95% CIs. Generalized least-squares trend estimation was used to assess dose-response relationships, with pooled summary estimates calculated by both fixed-effect and random-effect models. From 288 identified abstracts, 16 studies met inclusion criteria, including 18 separate cohorts comprising 540,184 individuals and 25,670 cases of incident DM. Consumption of fish and/or seafood was not significantly associated with DM (n=13 studies; RR per 100g/d=1.12, 95% CI=0.94, 1.34); nor were consumption of EPA+DHA (n=16 cohorts; RR per 250mg/d=1.04, 95% CI=0.97, 1.10) or circulating levels of EPA+DHA biomarkers (n=5 cohorts; RR per 3% of total fatty acids=0.94, 95% CI=0.75, 1.17). Both dietary ALA (n=7 studies; RR per 0.5g/d=0.93, 95% CI=0.83, 1.04) and circulating ALA biomarker levels (n=6 studies; RR per 0.1% of total fatty acid=0.90, 95% CI=0.80, 1.00, P=0.06) were associated with non-significant trend towards lower risk of DM. Substantial heterogeneity (I2~80%) was observed among studies of fish/seafood or EPA+DHA and DM; moderate heterogeneity (<55%) was seen for dietary and biomarker ALA and DM. In unadjusted meta-regressions, study location (Asia vs. North America/Europe), mean BMI, and duration of follow-up each modified the association between fish/seafood and EPA+DHA consumption and DM risk (P-Interaction ≤ 0.02 each). We had limited statistical power to determine the independent effect of these sources of heterogeneity due to their high collinearity. The overall pooled findings do not support either major harms or benefits of fish/seafood or EPA+DHA on development of DM, and suggest that ALA may be associated with modestly lower risk. Reasons for potential heterogeneity of effects, which could include true biologic heterogeneity, publication bias, or chance, deserve further investigation.",
"title": "Omega-3 Fatty Acids and incident Type 2 Diabetes: A Systematic Review and Meta-Analysis"
},
{
"docid": "MED-1466",
"text": "Rat muscle studies suggest competition between free fatty acids (FFA) and glucose for oxidation, resulting in glucose-6-phosphate accumulation. However, FFA decrease glucose-6-phosphate in human skeletal muscle, indicating direct inhibition of glucose transport/phosphorylation. This mechanism could redirect glucose from muscle to brain during fasting and explain the insulin resistance associated with high-lipid diets and obesity.",
"title": "How free fatty acids inhibit glucose utilization in human skeletal muscle."
},
{
"docid": "MED-3113",
"text": "Chronic diseases with a lifestyle-based aetiology currently make up a significant proportion of primary care consultations, but management often falls between the demands of public and clinical health. A modified clinical approach, based around the concept of \"lifestyle medicine\", helps fill the gap by adding behavioural, motivational and environmental skills to conventional medical practice. When used in a multidisciplinary setting, lifestyle medicine offers potential cost and effectiveness benefits, which are beginning to be realised.",
"title": "The emergence of \"lifestyle medicine\" as a structured approach for management of chronic disease."
}
] |
PLAIN-1545
|
luteolin
|
[
{
"docid": "MED-3548",
"text": "Cancer metastasis refers to the spread of cancer cells from the primary neoplasm to distant sites, where secondary tumors are formed, and is the major cause of death from cancer. Natural phytochemicals containing phenolic compounds have been widely demonstrated to have the capability to prevent cancer metastasis. Among phenolic compounds, flavonoids are a very large subclass, and they are abundant in food and nutraceuticals. The number of reports demonstrating that flavonoids are an effective natural inhibitor of cancer invasion and metastasis is increasing in the scientific literature. Catechin derivatives, (−)-epigallocatechin-3-gallate, (−)-epigallocatechin, (−)-epicatechin-3-gallate,and (−)-epicatechin, are the most studied compounds in this topic so far; genistein/genistin, silibinin, quercetin, and anthocyanin have also been widely investigated for their inhibitory activities on invasion/metastasis. Other flavonoids in dietary vegetable foods that are responsible for anti-invasive and anti-metastatic activities of tumors include luteolin,apigenin, myricetin, tangeretin, kaempferol, glycitein, licoricidin,daidzein, and naringenin. To effectively overcome the metastatic cascade, including cell-cell attachment, tissue barrier degradation, migration, invasion, cell-matrix adhesion,and angiogenesis, it is essential that a bioactive compound prevent tumor cells from metastasizing. This review summarizes the effects of flavonoids on the metastatic cascade and the related proteins, the in vitro anti-invasive activity of flavonoids against cancer cells, and the effects of flavonoids on antiangiogenic and in vivo anti-metastatic models. The available scientific evidence indicates that flavonoids are a ubiquitous dietary phenolics subclass and exert extensive in vitro anti-invasive and in vivo anti-metastatic activities.",
"title": "Flavonoids, a ubiquitous dietary phenolic subclass, exert extensive in vitro anti-invasive and in vivo anti-metastatic activities."
},
{
"docid": "MED-3553",
"text": "Several epidemiological studies have indicated that abundant consumption of foods from plant origin is associated with a reduced risk of developing several types of cancers. This chemopreventive effect is related to the high content of these foods in phytochemicals, such as polyphenols, that interfere with several processes involved in cancer progression including tumor cell growth, survival and angiogenesis. In addition to the low intake of plant-based foods, increased body mass and physical inactivity have recently emerged as other important lifestyle factors influencing cancer risk, leading to the generation of low-grade chronic inflammatory conditions which are a key process involved in tumor progression. The objectives of the current study are to investigate the inhibitory effects of these polyphenols on angiogenesis triggered by an inflammatory cytokine (IL-6) and to determine the mechanisms underlying this action. We found that, among the tested polyphenols, apigenin and luteolin were the most potent angiogenesis inhibitors through their inhibitory effect on the inflammatory cytokine IL-6/STAT3 pathway. These effects resulted in modulation of the activation of extracellular signal-regulated kinase-1/2 signaling triggered by IL-6, as well as in a marked reduction in the proliferation, migration and morphogenic differentiation of endothelial cells. Interestingly, these polyphenols also modulated the expression of IL-6 signal transducing receptor (IL-6Rα) and the secretion of the extracellular matrix degrading enzyme MMP-2 as well as the expression of suppressor of cytokine signaling (SOCS3) protein. Overall, these results may provide important new information on the role of diet in cancer prevention. Copyright © 2012 Elsevier Inc. All rights reserved.",
"title": "Diet-derived polyphenols inhibit angiogenesis by modulating the interleukin-6/STAT3 pathway."
},
{
"docid": "MED-3554",
"text": "A great deal of effort is now being devoted to the development of new drugs that hopefully will control the spread of inoperable cancer by safely inhibiting tumor-evoked angiogenesis. However, there is growing evidence that certain practical nutritional measures have the potential to slow tumor angiogenesis, and it is reasonable to anticipate that, by combining several measures that work in distinct but complementary ways to impede the angiogenic process, a clinically useful 'multifocal angiostatic therapy' (MAT) might be devised. Several measures which might reasonably be included in such a protocol are discussed below, and include: a low-fat, low-glycemic index vegan diet, which may down-regulate the systemic IGF-I activity that supports angiogenesis; supplemental omega-3-rich fish oil, which has been shown to inhibit endothelial expression of Flk-1, a functionally crucial receptor for VEGF, and also can suppress tumor production of pro-angiogenic eicosanoids; high-dose selenium, which has recently been shown to inhibit tumor production of VEGF; green tea polyphenols, which can suppress endothelial responsiveness to both VEGF and fibroblast growth factor; and high-dose glycine, whose recently reported angiostatic activity may reflect inhibition of endothelial cell mitosis, possibly mediated by activation of glycine-gated chloride channels. In light of evidence that tumor-evoked angiogenesis has a high requirement for copper, copper depletion may have exceptional potential as an angiostatic measure, and is most efficiently achieved with the copper-chelating drug tetrathiomolybdate. If logistical difficulties make it difficult to acquire this experimental drug, high-dose zinc supplementation can achieve a slower depletion of the body's copper pool, and in any case can be used as maintenance therapy to maintain an adequate level of copper depletion. A provisional protocol is offered for a nutritionally based MAT entailing a vegan diet and supplemental intakes of fish oil, selenium, green tea polyphenols, glycine, and zinc. Inasmuch as cox-2 is overexpressed in many cancers, and cAMP can boost tumor production of various angiogenic factors as well as autogenous growth factors, adjunctive use of cox-2-specific NSAIDS may be warranted in some cases.",
"title": "A wholly nutritional 'multifocal angiostatic therapy' for control of disseminated cancer."
},
{
"docid": "MED-3555",
"text": "A number of epidemiological studies have investigated associations between various phytochemicals and cancer risk. Phytoestrogens and carotenoids are the two most commonly studied classes of phytochemicals; phytosterols, isothiocyanates, and chlorophyll also have been investigated, although to a much lesser extent. Because there have been no systematic reviews of the literature on all phytochemicals and cancer risk to date, this article systematically reviews 96 published epidemiological studies that examined associations between phytochemicals and cancer risk. Most studies found null associations between individual phytochemicals and cancer risk at various sites. In addition, results from past studies have been largely inconsistent, and observed associations have been of relatively modest magnitude. The most consistent protective effects were observed for higher levels--dietary intake, serum, plasma, or urinary metabolites--of β-carotene and renal cell cancer, β-cryptoxanthin and lung cancer, isothiocyanates and lung cancer, isothiocyanates and gastrointestinal cancer, lignans and postmenopausal breast cancer, and flavonoids and lung cancer. Although elevated risk of certain cancers with higher levels of certain phytochemicals was observed, an insufficient pool of studies examining the same associations or inconsistent findings across studies limit the ability to conclude that any one phytochemical increases cancer risk. Additional research is needed to support previously identified associations in cases where only one study has examined a particular relationship. Importantly, continued research efforts are needed to evaluate the cumulative and interactive effects of numerous phytochemicals and phytochemical-rich foods on cancer risk.",
"title": "Phytochemicals and cancer risk: a review of the epidemiological evidence."
},
{
"docid": "MED-3549",
"text": "Studies have shown that fisetin, a small phytochemical molecule, has antitumor activity; however, its antiangiogenic activity has not yet been examined. Accordingly, herein, we investigated the antiangiogenic efficacy and associated mechanisms of fisetin in human umbilical vein endothelial cells (HUVECs). Fisetin (10-50 μM) strongly inhibited the regular serum plus growth supplement- and vascular endothelial growth factor (VEGF)-induced growth (up to 92%, P < 0.001) and survival (up to 16%, P < 0.001) of HUVEC in a dose- and time-dependent manner. Fisetin also caused cell cycle arrest at G(1) (strong) and G(2)/M (moderate) phases together with a decrease in cyclin D1 and an increase in p53 levels. Fisetin-caused cell death was accompanied by decreased expression of survivin and an increase in cleaved levels of caspases-3 and -7 and poly-(ADP-ribose) polymerase along with an increased ratio of Bax to Bcl-2. Furthermore, fisetin inhibited capillary-like tube formation on Matrigel (up to 85%, P < 0.001) as well as migration (up to 66%, P < 0.001), which were associated with decreased expression of endothelial nitric oxide synthase (eNOS) and VEGF in HUVEC. It also decreased the expression of eNOS, VEGF, inducible nitric oxide synthase, matrix metalloproteinase-2 and -9 in A549 and DU145 human cancer cells. In vivo matrigel plug assay in mice showed significant decrease in size (up to 43%, P < 0.001), vascularization and hemoglobin content (up to 94%, P < 0.001) in the plugs from fisetin-treated, compared with control mice. Overall, these results suggest that fisetin inhibits various attributes of angiogenesis, which might contribute to its reported antitumor effects, and therefore, fisetin warrants further investigation for its angiopreventive potential toward cancer control.",
"title": "Fisetin inhibits various attributes of angiogenesis in vitro and in vivo--implications for angioprevention."
},
{
"docid": "MED-3550",
"text": "Between 2000 and 2050, the number of new cancer patients diagnosed annually is expected to double, with an accompanying increase in treatment costs of more than $80 billion over just the next decade. Efficacious strategies for cancer prevention will therefore be vital for improving patients' quality of life and reducing healthcare costs. Judah Folkman first proposed antiangiogenesis as a strategy for preventing dormant microtumors from progressing to invasive cancer. Although antiangiogenic drugs are now available for many advanced malignancies (colorectal, lung, breast, kidney, liver, brain, thyroid, neuroendocrine, multiple myeloma, myelodysplastic syndrome), cost and toxicity considerations preclude their broad use for cancer prevention. Potent antiangiogenic molecules have now been identified in dietary sources, suggesting that a rationally designed antiangiogenic diet could provide a safe, widely available, and novel strategy for preventing cancer. This paper presents the scientific, epidemiologic, and clinical evidence supporting the role of an antiangiogenic diet for cancer prevention.",
"title": "Tumor Angiogenesis as a Target for Dietary Cancer Prevention"
},
{
"docid": "MED-3552",
"text": "The study evaluated the protective effects of purple rice (Oryza sativa L.) bran extract (PRE) and its constituents, cyanidin and peonidin, against angiogenesis induced by vascular endothelial growth factor (VEGF). The effects of VEGF and PRE were examined by in vitro tube formation assays and following 14-day co-culture of human umbilical vein endothelial cells (HUVECs) and fibroblasts. The antiangiogenic mechanism of PRE was evaluated by VEGF-induced proliferation and migration of HUVECs and/or human retinal microvascular endothelial cells (HRMECs) and phosphorylation of extracellular signal-regulated kinase (ERK) and p38. The PRE significantly suppressed VEGF-induced tube formation, proliferation and migration in HUVECs and HRMECs as well as phosphorylation of ERK and p38. Cyanidin and peonidin also suppressed the proliferation and migration induced by VEGF. These findings indicate that PRE and anthocyanidins suppress VEGF-induced angiogenesis by inhibiting proliferation and migration and suggest that the inhibition of phosphorylated-ERK and -p38 may be involved in the underlying mechanism. Copyright © 2011 John Wiley & Sons, Ltd.",
"title": "Purple rice (Oryza sativa L.) extract and its constituents inhibit VEGF-induced angiogenesis."
},
{
"docid": "MED-3551",
"text": "Breast cancer is the leading cause of cancer-related deaths for women in the United States and the rest of the world. About 8% of women develop breast cancer during the course of their lives. Dietary habits are closely associated with both the risk and progression of breast cancer. Dietary agents have accumulated increasing importance with regards to the prevention and treatment of breast cancer. One such manner by which these compounds can target breast cancer development and progression is through interference with the angiogenic pathways. Angiogenesis is an intricate process that involves the development of new capillaries from previously existing blood vessels. Disruption of this pathway, therefore, provides a novel and effective avenue for therapeutic intervention of breast cancer. Various phytochemicals found in the diet kill breast cancer cells in vitro and prevent as well as suppress breast cancer progression in various preclinical animal models. This review examines the value of dietary phytoconstituents in the prevention and treatment of breast cancer through modulation of the intricate and complex process of angiogenesis. In addition, the potential benefits, challenges, and future directions of research on anti-angiogenic dietary phytochemicals in the prevention and intervention of breast cancer are also addressed. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",
"title": "Modulation of angiogenesis by dietary phytoconstituents in the prevention and intervention of breast cancer."
}
] |
[
{
"docid": "MED-3158",
"text": "Various dietary flavonoids were evaluated in vitro for their inhibitory effect on xanthine oxidase, which has been implicated in oxidative injury to tissue by ischemia-reperfusion. Xanthine oxidase activity was determined by directly measuring uric acid formation by HPLC. The structure-activity relationship revealed that the planar flavones and flavonols with a 7-hydroxyl group such as chrysin, luteolin, kaempferol, quercetin, myricetin, and isorhamnetin inhibited xanthine oxidase activity at low concentrations (IC50 values from 0.40 to 5.02 microM) in a mixed-type mode, while the nonplanar flavonoids, isoflavones and anthocyanidins were less inhibitory. These results suggest that certain flavonoids might suppress in vivo the formation of active oxygen species and urate by xanthine oxidase.",
"title": "Inhibition of xanthine oxidase by flavonoids."
},
{
"docid": "MED-5045",
"text": "Helicobacter pylori (H. pylori) is one of the most widespread human pathogens, and plays major roles in chronic gastritis and gastric cancer. CD74 of gastric epithelial cells has recently been identified as an adhesion molecule to urease in H. pylori. In this study, we found that CD74 is highly expressed in a constitutive manner in NCI-N87 human gastric carcinoma cells at both the protein and mRNA levels as compared with Hs738St./Int fetal gastric cells. Subsequently, a novel cell-based ELISA able to rapidly screen the suppressive agents of CD74 expression was established. NCI-N87 cells were treated separately with 25 different food phytochemicals (4–100 µM) for 48 h and subjected to our novel assay. From those results, a citrus coumarin, bergamottin, was indicated to be the most promising compound with an LC50/IC50 value greater than 7.1, followed by luteolin (>5.4), nobiletin (>5.3), and quercetin (>5.1). Our findings suggest that these CD74 suppressants are unique candidates for preventing H. pylori adhesion and subsequent infection with reasonable action mechanisms.",
"title": "Suppressive Effects of Selected Food Phytochemicals on CD74 Expression in NCI-N87 Gastric Carcinoma Cells"
},
{
"docid": "MED-3476",
"text": "Fruit and vegetable consumption reduces the risk for cardiovascular disease development. The postprandial state is an important contributor to chronic disease development. Orange flavonoids may reduce postprandial oxidation. It was hypothesized that a mixture of orange flavonoids would reduce postprandial oxidation better than a single orange flavonoid or orange sugar and ascorbic acid, but not as well as orange juice, when consumed with a typical breakfast. A placebo-controlled crossover trial (16 male and female participants, 4 treatments, 4 visits) was carried out. Treatments were placebo (ascorbic acid and sugar equivalent to orange juice); placebo plus hesperidin; placebo plus hesperidin, luteolin, and naringenin (mixture; found to have synergistic antioxidant properties in vitro in previous work); and orange juice (positive control). Serum oxygen radical absorbance capacity (ORAC), total plasma phenolics (TP), and serum lipoprotein oxidation (LO) were measured after a 12-hour baseline fast and at 1, 2, and 3 hours after sample consumption. The placebo plus mixture and orange juice groups were significantly increased in ORAC and LO lag time. Data for TP were inconsistent with ORAC and LO. Contrary to previous studies attributing the protective postprandial effect to fructose and ascorbate in other fruit trials, orange phenolic compounds contribute directly to the postprandial oxidative protection of serum, despite an inconsistent change in serum TP. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "Controlling for sugar and ascorbic acid, a mixture of flavonoids matching navel oranges significantly increases human postprandial serum antioxidan..."
},
{
"docid": "MED-4863",
"text": "Chemical and cellular antioxidant activities and phenolic profiles of 11 lentil cultivars grown in the cool northern parts of the United States were investigated. Individual phenolic compounds, including phenolic acids, flavan-3-ols, flavones, and anthocyanins, were further quantitatively investigated by HPLC. Cellular antioxidant activities (CAA) and peroxyl radical scavenging capacity (PRSC) were evaluated by fluorescence microplate reader. Cultivar Morton exhibited the highest individual flavan-3-ols (catechin and epicatechin) and total flavonoids, as well as the highest antioxidant properties (PRSC and CAA) among all lentils tested. Five phenolic acids of the benzoic types and their derivates (gallic, protocatechuic, 2,3,4-trihydroxybenzoic, p-hydroxybenzoic acid, and protocatechualdehyde) and four phenolic acids of the cinnamic type (chlorogenic, p-coumaric, m-coumaric, and sinapic acid) were detected in all lentil cultivars. Two flavan-3-ols [(+)-catechin and (-)-epicatechin] and one flavone (luteolin) were detected in all lentil cultivars. Among all phenolic compounds detected, sinapic acid was the predominant phenolic acid, and (+)-catechin and (-)-epicatechin were the predominant flavonoids. These results showed that different phenotype lentils possessed considerable variations in their individual phenolic compounds, as well as chemical and cellular antioxidant activities. Caffeic acid, catechin, epicatechin, and total flavonoids significantly (p < 0.05) correlated with peroxyl radical scavenging assay. Cellular antioxidant assay significantly correlated with chemical antioxidant assay ORAC. The results from this study could be very interesting for breeding programs to improve lentils for use as functional foods.",
"title": "Phenolic substance characterization and chemical and cell-based antioxidant activities of 11 lentils grown in the northern United States."
},
{
"docid": "MED-3475",
"text": "Eight varieties of lettuce (Lactuca sativum) and three varieties of endive (Cichorium endivia) were analyzed for flavonoid composition and content. Total flavonoid contents, expressed as units of aglycon for fresh material, were in the ranges of 0.3-229 microg/g for lettuce and 44-248 microg/g for endive. Five quercetin conjugates [quercetin 3-O-galactoside, quercetin 3-O-glucoside, quercetin 3-O-glucuronide, quercetin 3-O-(6-O-malonyl)glucoside, and quercetin 3-O-rhamnoside] and luteolin 7-O-glucuronide were measured in the green-leafed lettuce and an additional two cyanidin conjugates [cyanidin 3-O-glucoside and cyanidin 3-O-[(6-O-malonyl)glucoside]] in the red-leafed varieties. Three kaempferol conjugates [kaempferol 3-O-glucoside, kaempferol 3-O-glucuronide, and kaempferol 3-O-[6-O-malonyl)glucoside]] were measured in each of the endive varieties. The presence and identity of kaempferol 3-O-(6-O-malonyl)glucoside in endive was shown for the first time. Shredding of lettuce leaf followed by exposure to light produced significant losses of the flavonoid moiety in the green oak leaf (94%), red oak leaf (43%), iceberg (36%), green batavia (25%), lollo biondo (24%), and lollo rosso (6%) samples, whereas cos and green salad bowl samples did not show an overall loss. Shredding of endive also produced loss of the flavonoid moiety in escarole (32%), fine frisee (13%), and coarse frisee (8%). Significant demalonation was observed for both the quercetin and cyanidin glucosides in lettuce, whereas a similar degradation of the kaempferol analogue was found in endive tissue. Storage of whole heads of both lettuce and endive in the dark at 1 degrees C and 98% humidity for 7 days resulted in losses of total flavonol glycosides in the range of 7-46%. The identification of the amounts, position of substitution, and nature of the sugars is important for understanding the potential bioavailability and biological activities of flavonoids in salads.",
"title": "Effect of variety, processing, and storage on the flavonoid glycoside content and composition of lettuce and endive."
},
{
"docid": "MED-1476",
"text": "The cave site of Moula-Guercy, 80 meters above the modern Rhone River, was occupied by Neanderthals approximately 100,000 years ago. Excavations since 1991 have yielded rich paleontological, paleobotanical, and archaeological assemblages, including parts of six Neanderthals. The Neanderthals are contemporary with stone tools and faunal remains in the same tightly controlled stratigraphic and spatial contexts. The inference of Neanderthal cannibalism at Moula-Guercy is based on comparative analysis of hominid and ungulate bone spatial distributions, modifications by stone tools, and skeletal part representations.",
"title": "Neanderthal cannibalism at Moula-Guercy, Ardèche, France."
},
{
"docid": "MED-3182",
"text": "OBJECTIVE: Review of human cysticercosis in Canada, to estimate the magnitude of the disease and to describe the pattern of disease expression in this country. METHODS: MEDLINE and manual search of case reports and case series of patients with cysticercosis diagnosed in Canada. ed data included year of diagnosis, citizenship status, clinical manifestations, and form of cysticercosis. FINDINGS: A total of 21 articles reporting 60 patients were found. Forty (67%) of these patients were diagnosed in the past two decades. Most cases came from Ontario (n=43) and Quebec (n=14). Immigrants accounted for 96% of the 28 cases in whom citizenship information was available. Neurocysticercosis was observed in 55 patients, and isolated compromise of striated muscles in the remaining five. Seizures was the primary or sole manifestation of the disease in 72% of patients, and most of them had parenchymal brain cysticerci (either viable cysts or calcifications). Two of seven patients were positive for Taenia eggs. In no case were household contacts of the patients investigated for taeniasis. CONCLUSIONS: An increasing number of patients with cysticercosis have been reported from Canada in the past two decades, suggesting that the prevalence of this parasitic disease may be on the rise. While most cases occur in immigrants, it is possible that at least some of these patients had acquired the disease in Canada.",
"title": "A review of cases of human cysticercosis in Canada."
},
{
"docid": "MED-1932",
"text": "There is increasing interest in discovering mechanisms that mediate the effects of childhood stress on late-life disease morbidity and mortality. Previous studies have suggested one potential mechanism linking stress to cellular aging, disease and mortality in humans: telomere erosion. We examined telomere erosion in relation to children’s exposure to violence, a salient early-life stressor, which has known long-term consequences for well-being and is a major public-health and social-welfare problem. In the first prospective-longitudinal study with repeated telomere measurements in children while they experienced stress, we tested the hypothesis that childhood violence exposure would accelerate telomere erosion from age 5 to age 10 years. Violence was assessed as exposure to maternal domestic violence, frequent bullying victimization and physical maltreatment by an adult. Participants were 236 children (49% females; 42% with one or more violence exposures) recruited from the Environmental-Risk Longitudinal Twin Study, a nationally representative 1994–1995 birth cohort. Each child’s mean relative telomere length was measured simultaneously in baseline and follow-up DNA samples, using the quantitative PCR method for T/S ratio (the ratio of telomere repeat copy numbers to single-copy gene numbers). Compared with their counterparts, the children who experienced two or more kinds of violence exposure showed significantly more telomere erosion between age-5 baseline and age-10 follow-up measurements, even after adjusting for sex, socioeconomic status and body mass index (B = −0.052, s.e. = 0.021, P = 0.015). This finding provides support for a mechanism linking cumulative childhood stress to telomere maintenance, observed already at a young age, with potential impact for life-long health.",
"title": "Exposure to violence during childhood is associated with telomere erosion from 5 to 10 years of age: a longitudinal study"
},
{
"docid": "MED-2427",
"text": "Lipid rafts/caveolae are membrane platforms for signaling molecules that regulate various cellular functions, including cell survival. To better understand the role of rafts in tumor progression and therapeutics, we investigated the effect of raft disruption on cell viability and compared raft levels in human cancer cell lines versus their normal counterparts. Here, we report that cholesterol depletion using methyl-β cyclodextrin caused anoikis-like apoptosis, which in A431 cells involved decreased raft levels, Bcl-xL down-regulation, caspase-3 activation, and Akt inactivation regardless of epidermal growth factor receptor activation. Cholesterol repletion replenished rafts on the cell surface and restored Akt activation and cell viability. Moreover, the breast cancer and the prostate cancer cell lines contained more lipid rafts and were more sensitive to cholesterol depletion-induced cell death than their normal counterparts. These results indicate that cancer cells contain increased levels of rafts and suggest a potential use of raft-modulating agents as anti-cancer drugs.",
"title": "Elevated Levels of Cholesterol-Rich Lipid Rafts in Cancer Cells Are Correlated with Apoptosis Sensitivity Induced by Cholesterol-Depleting Agents"
},
{
"docid": "MED-2245",
"text": "Curcumin (diferuloylmethane) is being considered as a potential chemopreventive agent in humans. In vitro it inhibits transcription by NF-kappaB, and the activity of lipoxygenase or cyclooxygenase enzymes, which facilitate tumor progression. In vivo it is protective in rodent models of chemical carcinogenesis. Curcumin contains an alpha,beta-unsaturated ketone, a reactive chemical substituent that is responsible for its repression of NF-kappaB. In compounds other than curcumin this same electrophilic moiety is associated with inactivation of the tumor suppressor, p53. Here we report that curcumin behaves analogously to these compounds. It disrupts the conformation of the p53 protein required for its serine phosphorylation, its binding to DNA, its transactivation of p53-responsive genes and p53-mediated cell cycle arrest.",
"title": "Curcumin impairs tumor suppressor p53 function in colon cancer cells."
},
{
"docid": "MED-855",
"text": "Hydrogen peroxide is an oxidising agent that is used in a number of household products, including general-purpose disinfectants, chlorine-free bleaches, fabric stain removers, contact lens disinfectants and hair dyes, and it is a component of some tooth whitening products. In industry, the principal use of hydrogen peroxide is as a bleaching agent in the manufacture of paper and pulp. Hydrogen peroxide has been employed medicinally for wound irrigation and for the sterilisation of ophthalmic and endoscopic instruments. Hydrogen peroxide causes toxicity via three main mechanisms: corrosive damage, oxygen gas formation and lipid peroxidation. Concentrated hydrogen peroxide is caustic and exposure may result in local tissue damage. Ingestion of concentrated (>35%) hydrogen peroxide can also result in the generation of substantial volumes of oxygen. Where the amount of oxygen evolved exceeds its maximum solubility in blood, venous or arterial gas embolism may occur. The mechanism of CNS damage is thought to be arterial gas embolisation with subsequent brain infarction. Rapid generation of oxygen in closed body cavities can also cause mechanical distension and there is potential for the rupture of the hollow viscus secondary to oxygen liberation. In addition, intravascular foaming following absorption can seriously impede right ventricular output and produce complete loss of cardiac output. Hydrogen peroxide can also exert a direct cytotoxic effect via lipid peroxidation. Ingestion of hydrogen peroxide may cause irritation of the gastrointestinal tract with nausea, vomiting, haematemesis and foaming at the mouth; the foam may obstruct the respiratory tract or result in pulmonary aspiration. Painful gastric distension and belching may be caused by the liberation of large volumes of oxygen in the stomach. Blistering of the mucosae and oropharyngeal burns are common following ingestion of concentrated solutions, and laryngospasm and haemorrhagic gastritis have been reported. Sinus tachycardia, lethargy, confusion, coma, convulsions, stridor, sub-epiglottic narrowing, apnoea, cyanosis and cardiorespiratory arrest may ensue within minutes of ingestion. Oxygen gas embolism may produce multiple cerebral infarctions. Although most inhalational exposures cause little more than coughing and transient dyspnoea, inhalation of highly concentrated solutions of hydrogen peroxide can cause severe irritation and inflammation of mucous membranes, with coughing and dyspnoea. Shock, coma and convulsions may ensue and pulmonary oedema may occur up to 24-72 hours post exposure. Severe toxicity has resulted from the use of hydrogen peroxide solutions to irrigate wounds within closed body cavities or under pressure as oxygen gas embolism has resulted. Inflammation, blistering and severe skin damage may follow dermal contact. Ocular exposure to 3% solutions may cause immediate stinging, irritation, lacrimation and blurred vision, but severe injury is unlikely. Exposure to more concentrated hydrogen peroxide solutions (>10%) may result in ulceration or perforation of the cornea. Gut decontamination is not indicated following ingestion, due to the rapid decomposition of hydrogen peroxide by catalase to oxygen and water. If gastric distension is painful, a gastric tube should be passed to release gas. Early aggressive airway management is critical in patients who have ingested concentrated hydrogen peroxide, as respiratory failure and arrest appear to be the proximate cause of death. Endoscopy should be considered if there is persistent vomiting, haematemesis, significant oral burns, severe abdominal pain, dysphagia or stridor. Corticosteroids in high dosage have been recommended if laryngeal and pulmonary oedema supervene, but their value is unproven. Endotracheal intubation, or rarely, tracheostomy may be required for life-threatening laryngeal oedema. Contaminated skin should be washed with copious amounts of water. Skin lesions should be treated as thermal burns; surgery may be required for deep burns. In the case of eye exposure, the affected eye(s) shod eye(s) should be irrigated immediately and thoroughly with water or 0.9% saline for at least 10-15 minutes. Instillation of a local anaesthetic may reduce discomfort and assist more thorough decontamination.",
"title": "Hydrogen peroxide poisoning."
},
{
"docid": "MED-4837",
"text": "BACKGROUND: Gallstone disease known as cholelithiasis is the most common digestive surgical disorder and account for an important part of health care expenditure. Attempt was made to analyse the gallstone for typing depending upon the composition. AIMS & OBJECTIVES: The main objective of this study was to see the prevalence of different types of gallstone in Nepal and to correlate them with the clinical findings. MATERIALS & METHODS: Gallstones of 80 different patients who underwent cholecystectomy for cholelithiasis were collected from 20th January 2005 to 16th May 2006 in Department of Pathology, Kathmandu Medical College Teaching Hospital. Detailed history was taken. Stones were analyzed with chemical and enzymatic methods using clinical spectrophotometer. RESULTS & CONCLUSION: The most commonly involved age group for cholelithiasis (32.5%) is found to be 30-39 years with a female predominance (M: F=1:3.2). Cholelithiasis was found more commonly among non-vegetarian with the vegetarian: non-vegetarian ratio 1:9. Mixed type stone was found to be the most common type of stone comprising 78.75%, followed by cholesterol stone 12.5%, Brown pigment stone 7.5% and Black pigment stone 1.25%.",
"title": "Prevalence of different types of gallstone in the patients with cholelithiasis at Kathmandu Medical College, Nepal."
},
{
"docid": "MED-4027",
"text": "Objectives To study the dietary behavior and knowledge about dental erosion and self-reported symptoms that can be related to dental erosion among Chinese adults in Hong Kong. Methods Chinese adults aged 25-45 years were randomly selected from a list of registered telephone numbers generated by computer. A telephone survey was administered to obtain information on demographic characteristics, dietary habits, dental visits, and knowledge of and presence of self-reported symptoms that can be related to dental erosion. Results A total of 520 participants were interviewed (response rate, 75%; sampling error, ± 4.4%) and their mean age was 37. Most respondents (79%) had ever had caries, and about two thirds (64%) attended dental check-ups at least once a year. Respondents had a mean of 5.4 meals per day and 36% had at least 6 meals per day. Fruit (89%) and lemon tea/water (41%) were the most commonly consumed acidic food and beverage. When asked if they ever noticed changes in their teeth, most respondents (92%) said they had experienced change that can be related to erosion. However, many (71%) had never heard about dental erosion and 53% mixed up dental erosion with dental caries. Conclusion Hong Kong Chinese adults have frequent intake of food and many have experienced symptoms that can be related to dental erosion. Their level of awareness of and knowledge about dental erosion is generally low, despite most of them have regular dental check-ups. Dental health education is essential to help the public understand dental erosion and its damaging effects.",
"title": "Dietary behavior and knowledge of dental erosion among Chinese adults"
},
{
"docid": "MED-1112",
"text": "Because of the central role of the transcription factor nuclear factor-kappaB (NF-kappaB) in cell survival and proliferation in human multiple myeloma (MM), we explored the possibility of using it as a target for MM treatment by using curcumin (diferuloylmethane), an agent known to have very little or no toxicity in humans. We found that NF-kappaB was constitutively active in all human MM cell lines examined and that curcumin, a chemopreventive agent, down-regulated NF-kappaB in all cell lines as indicated by electrophoretic mobility gel shift assay and prevented the nuclear retention of p65 as shown by immunocytochemistry. All MM cell lines showed consitutively active IkappaB kinase (IKK) and IkappaBalpha phosphorylation. Curcumin suppressed the constitutive IkappaBalpha phosphorylation through the inhibition of IKK activity. Curcumin also down-regulated the expression of NF-kappaB-regulated gene products, including IkappaBalpha, Bcl-2, Bcl-x(L), cyclin D1, and interleukin-6. This led to the suppression of proliferation and arrest of cells at the G(1)/S phase of the cell cycle. Suppression of NF-kappaB complex by IKKgamma/NF-kappaB essential modulator-binding domain peptide also suppressed the proliferation of MM cells. Curcumin also activated caspase-7 and caspase-9 and induced polyadenosine-5'-diphosphate-ribose polymerase (PARP) cleavage. Curcumin-induced down-regulation of NF-kappaB, a factor that has been implicated in chemoresistance, also induced chemosensitivity to vincristine and melphalan. Overall, our results indicate that curcumin down-regulates NF-kappaB in human MM cells, leading to the suppression of proliferation and induction of apoptosis, thus providing the molecular basis for the treatment of MM patients with this pharmacologically safe agent.",
"title": "Curcumin (diferuloylmethane) down-regulates the constitutive activation of nuclear factor-kappa B and IkappaBalpha kinase in human multiple myeloma..."
},
{
"docid": "MED-1607",
"text": "Background: As sodium, potassium and fluid intake are related to hypertension, an established risk factor for renal cell cancer (RCC), they may be independent risk factors for RCC. Methods: The Netherlands Cohort Study (NLCS) with case-cohort design included 120 852 participants aged 55–69 years. At baseline, diet and lifestyle were assessed with questionnaires. After 17.3 years of follow-up, 485 RCC cases and 4438 subcohort members were available for analyses. Results: Sodium intake increased RCC risk (P-trend=0.03), whereas fluid and potassium intake did not. For high sodium and low fluid intake, the RCC risk additionally increased (P-interaction=0.02). Conclusion: Sodium intake is a potential risk factor for RCC, particularly if fluid consumption is low.",
"title": "Long-term dietary sodium, potassium and fluid intake; exploring potential novel risk factors for renal cell cancer in the Netherlands Cohort Study on diet and cancer"
},
{
"docid": "MED-4825",
"text": "Pancreatic cancer kills more than 250,000 people each year worldwide and has a poor prognosis. The aim of this article is to critically review the epidemiologic evidence for exposures that may either increase or decrease the risk. A Medline search was performed for epidemiologic studies and reviews published up to April 2007. Consistent evidence of a positive association was found for family history and cigarette smoking. Many studies documented a positive association with diabetes mellitus and chronic pancreatitis, although the etiologic mechanisms are unclear. Other associations were detected, but the results were either inconsistent or from few studies. These included positive associations with red meat, sugar, fat, body mass index, gallstones, and Helicobacter pylori, and protective effects of increasing parity, dietary folate, aspirin, and statins. There was no evidence linking alcohol or coffee consumption with an increased risk of pancreatic cancer. The associations with many exposures need to be clarified from further epidemiologic work in which there is both precise measurement of risk factors, adjustment for potential confounders, and, for dietary studies, information recorded on the method of food preparation and pattern of consumption. Such work is important to reduce the incidence of this fatal disease.",
"title": "Pancreatic cancer: a review of the evidence on causation."
},
{
"docid": "MED-1249",
"text": "The effect of dietary protein on the level of plasma cholesterol in young, healthy, normolipidemic women was investigated in two separate studies by feeding either a conventional diet containing mixed protein, or a plant protein diet in which the animal protein of the first diet was replaced by soy protein meat analogues and soy milk. The diets were similar with respect to carbohydrate, fat and sterol composition. The first study, lasting 73 days and involving six subjects, gave an indication that plasma cholesterol levels were lower on the plant protein diet. The second study, which incorporated a number of improvements based on experience, lasted 78 days and used a cross-over design involving two groups of five subjects each. In this study, the mean plasma cholesterol level was found to be significantly lower on the plant protein diet.",
"title": "Hypocholesterolemic effect of substituting soybean protein for animal protein in the diet of healthy young women."
},
{
"docid": "MED-4620",
"text": "Phytochemicals are recognized as playing an important role in cancer prevention by fruits and vegetables. The avocado is a widely grown and consumed fruit that is high in nutrients and low in calories, sodium, and fats. Studies have shown that phytochemicals extracted from the avocado fruit selectively induce cell cycle arrest, inhibit growth, and induce apoptosis in precancerous and cancer cell lines. Our recent studies indicate that phytochemicals extracted with chloroform from avocado fruits target multiple signaling pathways and increase intracellular reactive oxygen leading to apoptosis. This review summarizes the reported phytochemicals in avocado fruit and discusses their molecular mechanisms and targets. These studies suggest that individual and combinations of phytochemicals from the avocado fruit may offer an advantageous dietary strategy in cancer prevention.",
"title": "Chemopreventive characteristics of avocado fruit."
},
{
"docid": "MED-3130",
"text": "Although soy phytoestrogens have been postulated to exert a protective effect against breast cancer, the attendant mechanisms, in particular epigenetics underpinnings, have remained elusive. We investigated the putative effects on DNA methylation by two naturally occurring isoflavones, genistein and daidzein, in a study of the BRCA1 and BRCA2 oncosuppressor genes in breast cancer cell lines (MCF-7, MDA-MB 231, and MCF10a). A demethylant agent, the 5-azacytidine, and a methylant, the budesonide, were used as treatment controls. DNA methylation of BRCA1 and BRCA2 was investigated with methylated DNA immunoprecipitation coupled with PCR. In parallel, protein expression was determined by Western blot, immunohistochemistry, and confocal microscopy. Our results suggest that treatment with 18.5 μM Genistein or 78.5 μM Daidzein might reverse DNA hypermethylation and restore the expression of the oncosuppressor genes BRCA1 and BRCA2. 5-Azacitydine also enhanced the reexpression of these genes while budesonide had an opposite effect. To the best of our knowledge, these observations, while requiring replication, provide new evidence on potential epigenetic mechanisms by which genistein and daidzein might contribute to regulation of the BRCA1 and BRCA2. Future studies are warranted on whether the demethylating effect of genistein and daidzein is global or focused on select candidate genes.",
"title": "Can soy phytoestrogens decrease DNA methylation in BRCA1 and BRCA2 oncosuppressor genes in breast cancer?"
},
{
"docid": "MED-3451",
"text": "Oxidative stress is a natural physiological process that describes an imbalance between free radical production and the ability of the antioxidant defence system of the body to neutralize free radicals. Free radicals can be beneficial as they may promote wound healing and contribute to a healthy immune response. However, free radicals can have a detrimental impact when they interfere with the regulation of apoptosis and thus play a role in the promotion of some cancers and conditions such as cardiovascular disease. Antioxidants are molecules that reduce the damage associated with oxidative stress by counteracting free radicals. Regular exercise is a vital component of a healthy lifestyle, although it can increase oxidative stress. As a typical vegetarian diet comprises a wide range of antioxidant-rich foods, it is plausible that the consumption of these foods will result in an enhanced antioxidant system capable of reducing exercise-induced oxidative stress. In addition, a relationship between a vegetarian diet and lower risks of cardiovascular disease and some cancers has been established. This review explores the current available evidence linking exercise, vegetarians, antioxidants, and oxidative stress.",
"title": "Could a vegetarian diet reduce exercise-induced oxidative stress? A review of the literature."
},
{
"docid": "MED-4733",
"text": "OBJECTIVES: Mercury and most of its compounds are extremely toxic and should be handled with care. It can be inhaled and absorbed through the skin and mucous membranes. The most toxic forms of mercury are its organic compounds such as dimethylmercury and methylmercury. Fish have a natural tendency to accumulate mercury. Methylmercury is produced by microbial methylation of inorganic mercury in water sediment then it infiltrates the food chain and it consequently accumulates in fish. Fish are the main source of methylmercury in human food. Mercury is transferred into a hair; and this can be than used to monitor the long-term exposure to mercury. The content of mercury in hair depends on the frequency of fish consumption. The aim of our study was to compare mercury content in the hair of children that had various amounts of fish consumption (increased or reduced). DESIGN: Total mercury content in hair was determined by direct method of cold vapors using an AMA 245 analyzer. A total of 174 hair samples from the children (9-17 years old) were analyzed. In this study, the following localities were compared: Neratovice (n=42), Jeseníky (n=44), Prague (n=59) in Czech Republic and Olsztyn in Poland (n=29). Every sample was accompanied with questionnaire about age, gender, regions, amalgam fillings and fish consumption. RESULTS: We did not find a correlation between the content of mercury in hair with age, gender or amalgam fillings. We did find a correlation between fish consumption and the amount of mercury found in the hair samples. CONCLUSION: The amount of mercury in hair increases with more frequent consumption of freshwater and marine fish.",
"title": "Mercury in human hair as an indicator of the fish consumption."
},
{
"docid": "MED-4516",
"text": "There is limited knowledge about the possible effect of unabsorbed dietary antioxidants that reach the large intestine on bowel habits. The aim of the present study was to investigate whether a dietary recommendation directed to increase diet total antioxidant capacity (TAC) is able to affect gut function in human subjects. In this cross-over intervention, nineteen subjects followed a high-TAC (HT) and a low-TAC (LT) diet for 2 weeks, which were comparable for energy, macronutrient, total dietary fibre and alcohol contents. At the end of each intervention period, the 48 h stool output was recorded. In the faecal samples obtained from a subset of nine subjects, moisture, pH, ammonia content, Lactobacillus and Bifidobacterium counts, faecal water antioxidants and genotoxicity were measured. A 3 d weighed food record was used to assess the diet composition during HT and LT diet intake. Significant increases in the intake of TAC, vitamins E and C and phenolic compounds were observed during the HT diet intake. The higher intake of antioxidants led to increased 48 h stool output (324 (SD 38) g in HT v. 218 (SD 22) g in LT), and to higher TAC and total phenolic concentrations in faecal water. No significant variation in the other measured parameters was observed between the diets. In conclusion, a diet selected to raise the intake of dietary antioxidants is able to increase stool bulk and antioxidant content of faeces.",
"title": "Ability of a high-total antioxidant capacity diet to increase stool weight and bowel antioxidant status in human subjects."
},
{
"docid": "MED-830",
"text": "Water-soluble polysaccharides were separated from maca (Lepidium meyenii) aqueous extract (MAE). The crude polysaccharides were deproteinized by Sevag method. During the preparation process of maca polysaccharides, amylase and glucoamylase effectively removed starch in maca polysaccharides. Four Lepidium meyenii polysaccharides (LMPs) were obtained by changing the concentration of ethanol in the process of polysaccharide precipitation. All of the LMPs were composed of rhamnose, arabinose, glucose and galactose. Antioxidant activity tests revealed that LMP-60 showed good capability of scavenging hydroxyl free radical and superoxide radical at 2.0mg/mL, the scavenging rate was 52.9% and 85.8%, respectively. Therefore, the results showed that maca polysaccharides had a high antioxidant activity and could be explored as the source of bioactive compounds. Copyright © 2014 Elsevier Ltd. All rights reserved.",
"title": "Extraction, purification and antioxidant activities of the polysaccharides from maca (Lepidium meyenii)."
},
{
"docid": "MED-4707",
"text": "Background: Data concerning the long-term association between nut consumption and weight change in a free-living population are sparse. Objective: The objective was to determine the relation between nut consumption and long-term weight change. Design: The participants were 51,188 women in the Nurses' Health Study II aged 20–45 y, who had no cardiovascular disease, diabetes, or cancer. We prospectively evaluated the dietary intake of nuts and subsequent weight changes from 1991 to 1999. Results: Women who reported eating nuts ≥2 times/wk had slightly less mean (± SE) weight gain (5.04 ± 0.12 kg) than did women who rarely ate nuts (5.55 ± 0.04 kg) (P for trend < 0.001). For the same comparison, when total nut consumption was subdivided into peanuts and tree nuts, the results were similar (ie, less weight gain in women eating either peanuts or tree nuts ≥2 times/wk). The results were similar in normal-weight, overweight, and obese participants. In multivariate analyses in which lifestyle and other dietary factors were controlled for, we found that greater nut consumption (≥2 times/wk compared with never/almost never) was associated with a slightly lower risk of obesity (hazard ratio: 0.77; 95% CI: 0.57, 1.02; P for trend = 0.003). Conclusions: Higher nut consumption was not associated with greater body weight gain during 8 y of follow-up in healthy middle-aged women. Instead, it was associated with a slightly lower risk of weight gain and obesity. The results of this study suggest that incorporating nuts into diets does not lead to greater weight gain and may help weight control.",
"title": "Prospective study of nut consumption, long-term weight change, and obesity risk in women"
},
{
"docid": "MED-4617",
"text": "The need for consistent and current data describing the true incidence of SCA and/or SCD was highlighted during the most recent Sudden Cardiac Arrest Thought Leadership Alliance’s (SCATLA) Think Tank meeting of national experts with broad representation of key stakeholders including thought leaders and representatives from the American College of Cardiology, American Heart Association, and the Heart Rhythm Society. As such, to evaluate the true magnitude of this public health problem, we performed a systematic literature search in MEDLINE using the MeSH headings, “death, sudden” OR the terms “sudden cardiac death” OR “sudden cardiac arrest” OR “cardiac arrest” OR “cardiac death” OR “sudden death” OR “arrhythmic death.” Study selection criteria included peer-reviewed publications of primary data used to estimate SCD incidence in the U.S. We used Web of Science®’s Cited Reference Search to evaluate the impact of each primary estimate on the medical literature by determining the number of times each “primary source” has been cited. The estimated U.S. annual incidence of SCD varied widely from 180,000 to > 450,000 among 6 included studies. These different estimates were in part due to different data sources (with data age ranging from 1980 to 2007), definitions of SCD, case ascertainment criteria, methods of estimation/extrapolation, and sources of case ascertainment. The true incidence of SCA and/or SCD in the U.S. remains unclear with a wide range in the available estimates, which are badly dated. As reliable estimates of SCD incidence are important for improving risk stratification and prevention, future efforts are clearly needed to establish uniform definitions of SCA and SCD and then to prospectively and precisely capture cases of SCA and SCD in the overall U.S. population.",
"title": "Systematic Review of the Incidence of Sudden Cardiac Death in the United States"
},
{
"docid": "MED-3980",
"text": "Background Pet ownership is thought to have health benefits, but not all scientific explorations have been founded on proper applications of representative samples or statistically correct methodologies. Databanks have been too small for proper statistical analyses; or, instead of a random sample, participation has been voluntary. The direction of causality has been evaluated incorrectly or control of relevant factors noted deficient. This study examined the associations of pet ownership with perceived health and disease indicators by taking into account socio-demographic background factors together with health risk factors, including exercise. Methodology/Principal Findings The present study used baseline data from the 15-year Health and Social Support Study (the HeSSup Study). The Finnish Population Register Centre was used to draw population-based random samples stratified according to gender and four age groups (20–24, 30–34, 40–44, and 50–54 years). A total of 21,101 working-aged Finns responded to the baseline survey questionnaire of the 15-year HeSSup Study in 1998. Ordinal and binary logistic regression was used to analyze the cross-sectional data. Pet ownership was associated with poor rather than good perceived health. BMI surfaced as the risk factor most strongly associated with pet ownership. Conclusions/Significance Pet owners set in their ways and getting older were found to have a slightly higher BMI than the rest. Additional research is needed for the testing of hypotheses involving effects of pet ownership with various health dimensions within population groups that are composed of different kinds of background characteristics.",
"title": "To Have or Not To Have a Pet for Better Health?"
},
{
"docid": "MED-743",
"text": "OBJECTIVE: To evaluate herbal medicines, other than St. John's wort, in the treatment of depression. DATA SOURCES/SEARCH METHODS: A computer-based search of Medline, Cinahl, AMED, ALT Health Watch, Psych Articles, Psych Info, Current Contents databases, Cochrane Controlled Trials Register, and Cochrane Database of Systematic Reviews, was performed. Researchers were contacted, and bibliographies of relevant papers and previous meta-analysis were hand searched for additional references. REVIEW METHODS: Trials were included in the review if they were prospective human trials assessing herbal medicines, other than St. John's wort, in the treatment of mild-to-moderate depression and utilized validated instruments to assess participant eligibility and clinical endpoints. RESULTS: Nine trials were identified that met all eligibility requirements. Three studies investigated saffron stigma, two investigated saffron petal, and one compared saffron stigma to the petal. Individual trials investigating lavender, Echium, and Rhodiola were also located. DISCUSSION: Results of the trials are discussed. Saffron stigma was found to be significantly more effective than placebo and equally as efficacious as fluoxetine and imipramine. Saffron petal was significantly more effective than placebo and was found to be equally efficacious compared to fluoxetine and saffron stigma. Lavender was found to be less effective than imipramine, but the combination of lavender and imipramine was significantly more effective than imipramine alone. When compared to placebo, Echium was found to significantly decrease depression scores at week 4, but not week 6. Rhodiola was also found to significantly improve depressive symptoms when compared to placebo. CONCLUSION: A number of herbal medicines show promise in the management of mild-to-moderate depression.",
"title": "Herbal medicines, other than St. John's Wort, in the treatment of depression: a systematic review."
},
{
"docid": "MED-4411",
"text": "Chronic obstructive pulmonary disease (COPD) is characterised by increased oxidative stress. Dietary factors, such as ample consumption of foods rich in antioxidants, such as fruit and vegetables, might have beneficial effects in COPD patients. The association between dietary shift to foods rich in antioxidants and lung function in COPD was investigated in a 3-yr prospective study. A total of 120 COPD patients were randomised to follow either a diet based on increased consumption of fresh fruit and vegetables (intervention group (IG)) or a free diet (control group (CG)). The mean consumption of foods containing antioxidants was higher in the IG than in the CG throughout the study period (p<0.05). The relationship between consumption of foods rich in antioxidants and percentage predicted forced expiratory volume in 1 s was assessed using a general linear model for repeated measures; the two groups overall were different in time (p = 0.03), with the IG showing a better outcome. In investigating the effect of several confounders (sex, age, smoking status, comorbid conditions and exacerbation) of group response over time, nonsignificant interactions were found between confounders, group and time. These findings suggest that a dietary shift to higher-antioxidant food intake may be associated with improvement in lung function, and, in this respect, dietary interventions might be considered in COPD management.",
"title": "Impact of dietary shift to higher-antioxidant foods in COPD: a randomised trial."
},
{
"docid": "MED-1063",
"text": "BACKGROUND: The results of some epidemiologic studies conducted by using questionnaires suggest that dietary fat composition influences diabetes risk. Confirmation of this finding with use of a biomarker is warranted. OBJECTIVE: We prospectively investigated the relation of plasma cholesterol ester (CE) and phospholipid (PL) fatty acid composition with the incidence of diabetes mellitus. DESIGN: In 2909 adults aged 45-64 y, plasma fatty acid composition was quantified by using gas-liquid chromatography and was expressed as a percentage of total fatty acids. Incident diabetes (n = 252) was identified during 9 y of follow-up. RESULTS: After adjustment for age, sex, baseline body mass index, waist-to-hip ratio, alcohol intake, cigarette smoking, physical activity, education, and parental history of diabetes, diabetes incidence was significantly and positively associated with the proportions of total saturated fatty acids in plasma CE and PL. The rate ratios of incident diabetes across quintiles of saturated fatty acids were 1.00, 1.36, 1.16, 1.60, and 2.08 (P = 0.0013) in CE and 1.00, 1.75, 1.87, 2.40, and 3.37 (P < 0.0001) in PL. In CE, the incidence of diabetes was also positively associated with the proportions of palmitic (16:0), palmitoleic (16:1n-7), and dihomo-gamma-linolenic (20:3n-6) acids and inversely associated with the proportion of linoleic acid (18:2n-6). In PL, incident diabetes was positively associated with the proportions of 16:0 and stearic acid (18:0). CONCLUSIONS: The proportional saturated fatty acid composition of plasma is positively associated with the development of diabetes. Our findings with the use of this biomarker suggest indirectly that the dietary fat profile, particularly that of saturated fat, may contribute to the etiology of diabetes.",
"title": "Plasma fatty acid composition and incidence of diabetes in middle-aged adults: the Atherosclerosis Risk in Communities (ARIC) Study."
},
{
"docid": "MED-4697",
"text": "Summary With the aging of the population, we are seeing a global increase in age-related disorders, especially in developed countries. Chronic diseases disproportionately affect the older segment of the population, contributing to disability, a diminished quality of life, and an increase in healthcare costs. Increased life expectancy reflects the success of contemporary medicine, which must now respond to the challenges created by this achievement, including the growing burden of chronic illnesses, injuries, and disabilities. A well-developed theoretical framework is required to understand the molecular basis of aging. This, in turn, is a prerequisite for developing the clinical interventions that will constitute an efficient response to the challenge of age-related health issues. This review critically analyzes the experimental evidence that supports and refutes the Free Radical/Mitochondrial Theory of Aging, which has dominated the field of aging research for almost half a century.",
"title": "Is there more to aging than mitochondrial DNA and reactive oxygen species?"
}
] |
4475
|
How would bonds fare if interest rates rose?
|
[
{
"docid": "599436",
"text": "\"1. Interest rates What you should know is that the longer the \"\"term\"\" of a bond fund, the more it will be affected by interest rates. So a short-term bond fund will not be subject to large gains or losses due to rate changes, an intermediate-term bond fund will be subject to moderate gains or losses, and a long-term bond fund will be subject to the largest gains or losses. When a book or financial planner says to buy \"\"bonds\"\" with no other qualification, they almost always mean investment-grade intermediate-term bond funds (or for individual bonds, the equivalent would be a bond ladder averaging an intermediate term). If you want technical details, look at the \"\"average duration\"\" or \"\"average maturity\"\" of the bond fund; as a rough guide, if the duration is 10, then a 1% change in interest rates would be a 10% gain or loss on the fund. Another thing you can do is look at long-term (10 years or ideally longer) performance history on some short, intermediate, and long term bond index funds, and you can see how the long term funds bounced around more. Non-investment-grade bonds (aka junk bonds or high yield bonds) are more affected by factors other than interest rates, including some of the same factors (economic booms or recessions) that affect stocks. As a result, they aren't as good for diversifying a portfolio that otherwise consists of stocks. (Having stocks, investment grade bonds, and also a little bit in high-yield bonds can add diversification, though. Just don't replace your bond allocation with high-yield bonds.) A variety of \"\"complicated\"\" bonds exist (convertible bonds are an example) and these are tough to analyze. There are also \"\"floating rate\"\" bonds (bank loan funds), these have minimal interest rate sensitivity because the rate goes up to offset rate rises. These funds still have credit risks, in the credit crisis some of them lost a lot of money. 2. Diversification The purpose of diversification is risk control. Your non-bond funds will outperform in many years, but in other years (say the -37% S&P 500 drop in 2008) they may not. You will not know in advance which year you'll get. You get risk control in at least a few ways. There's also an academic Modern Portfolio Theory explanation for why you should diversify among risky assets (aka stocks), something like: for a given desired risk/return ratio, it's better to leverage up a diverse portfolio than to use a non-diverse portfolio, because risk that can be eliminated through diversification is not compensated by increased returns. The theory also goes that you should choose your diversification between risk assets and the risk-free asset according to your risk tolerance (i.e. select the highest return with tolerable risk). See http://en.wikipedia.org/wiki/Modern_portfolio_theory for excruciating detail. The translation of the MPT stuff to practical steps is typically, put as much in stock index funds as you can tolerate over your time horizon, and put the rest in (intermediate-term investment-grade) bond index funds. That's probably what your planner is asking you to do. My personal view, which is not the standard view, is that you should take as much risk as you need to take, not as much as you think you can tolerate: http://blog.ometer.com/2010/11/10/take-risks-in-life-for-savings-choose-a-balanced-fund/ But almost everyone else will say to do the 80/20 if you have decades to retirement and feel you can tolerate the risk, so my view that 60/40 is the max desirable allocation to stocks is not mainstream. Your planner's 80/20 advice is the standard advice. Before doing 100% stocks I'd give you at least a couple cautions: See also:\"",
"title": ""
},
{
"docid": "31581",
"text": "When interest rates rise, the price of bonds fall because bonds have a fixed coupon rate, and since the interest rate has risen, the bond's rate is now lower than what you can get on the market, so it's price falls because it's now less valuable. Bonds diversify your portfolio as they are considered safer than stocks and less volatile. However, they also provide less potential for gains. Although diversification is a good idea, for the individual investor it is far too complicated and incurs too much transaction costs, not to mention that rebalancing would have to be done on a regular basis. In your case where you have mutual funds already, it is probably a good idea to keep investing in mutual funds with a theme which you understand the industry's role in the economy today rather than investing in some special bonds which you cannot relate to. The benefit of having a mutual fund is to have a professional manage your money, and that includes diversification as well so that you don't have to do that.",
"title": ""
}
] |
[
{
"docid": "506743",
"text": "what will happen to the valuation of Tom's bond holdings after the equity crash? This is primarily opinion based. What will happen is generally hard to predict. Bond Price Bump due to Demand: Is a possible outcome; this depends on the assumption that the bonds in the said country are still deemed safe. Recent Greece example, this may not be true. So if the investors don't believe that Bonds are safe, the money may move into Real Estate, into Bullion [Gold etc], or to other markets. In such a scenario; the price may not bump up. Bond Price Decline due to Rising Interest Rates: On a rising interest rates, the long-term bonds may loose in value while the short term bonds may hold their value. Related question How would bonds fare if interest rates rose?",
"title": ""
},
{
"docid": "440856",
"text": "No, they are not recession proof. Assume several companies, that issued bonds in the fund, go bankrupt. Those bonds could be worthless, they could miss principle payments, or they could be restructured. All would mean a decline in value. When the economy shrinks (which is what a recession is) how does the Fed respond? By lowering interest rates. This makes current bonds more valuable as presumably they were issued at a higher rate, thus the recession proof prejudice. However, there is nothing to stop a company (in good financial shape) from issuing more bonds to pay the par value on high-interest bonds, thus refinancing their debt. Sort of like how the bank feels when one refinances the mortgage for a lower rate. The thing that troubles me the most is that rates have been low for a long time. What happens if we have a recession now? How does the Fed fix it? I am not sure exactly what the fallout would be, but it could be significant. If you are troubled, you should look for sectors that would be hurt and helped by a Trump-induced recession. Move money away from those that will be hurt. Typically aggressive growth companies are hurt (during recessions), so you may want to move money away from them. Typically established blue chip companies fare okay in a recession so you may want to move money toward them. Move some money to cash, and perhaps some towards bonds. All that being said, I'd keep some money in things like aggressive growth in case you are wrong.",
"title": ""
},
{
"docid": "551590",
"text": "\"From http://blog.ometer.com/2008/03/27/index-funds/ , Lots of sensible advisers will tell you to buy index funds, but importantly, the advice is not simply \"\"buy index funds.\"\" There are at least two other critical details: 1) asset allocation across multiple well-chosen indexes, maintained through regular rebalancing, and 2) dollar cost averaging (or, much-more-complex-but-probably-slightly-better, value averaging). The advice is not to take your single lump sum and buy and hold a cap-weighted index forever. The advice is an investment discipline which involves action over time, and an initial choice among indexes. An index-fund-based strategy is not completely passive, it involves some active risk control through rebalancing and averaging. If you'd held a balanced portfolio over the last ten years and rebalanced, and even better if you'd dollar cost averaged, you'd have done fine. Your reaction to the last 10 years incidentally is why I don't believe an almost-all-stocks allocation makes sense for most people even if they're pretty young. More detail in this answer: How would bonds fare if interest rates rose? I think some index fund advocacy and books do people a disservice by focusing too much on the extra cost of active management and why index funds are a good deal. That point is true, but for most investors, asset allocation, rebalancing, and \"\"autopilotness\"\" of their setup are more important to outcome than the expense ratio.\"",
"title": ""
},
{
"docid": "567749",
"text": "The US Treasury is not directly/transactionally involved, but can affect the junk bond market by issuing new bonds when rates rise. Since US bonds are considered completely safe, changes in yield will affect low quality debt. For example, if rates rose to levels like 1980, a 12% treasury bond would drive the prices of junk bonds issued today dramatically lower. Another price factor is likelihood of default. Companies with junk credit ratings have lousy balance sheets, so negative economic conditions or tight short term debt markets can result in default for many of these companies. Whether bonds in a fund are new issues or purchased on the secondary market isn't something that is very relevant to the individual investor. The current interest rate environment is factored into the market already via prices of bonds.",
"title": ""
},
{
"docid": "590364",
"text": "Bonds released at the same time have different interest rates because they have different levels of risks and liquidity associated. Risk will depend on the company / country / municipality that offers the bond: their financial position, and their resulting ability to make future payments & avoid default. Riskier organizations must offer higher interest rates to ensure that investors remain willing to loan them money. Liquidity depends on the terms of the loan - principal-only bonds give you minimal liquidity, as there are no ongoing interest payments, and nothing received until the bond's maturity date. All bonds provide lower liquidity if they have longer maturity dates. Bonds with lower liquidity must have higher returns to compensate for the fact that you will have to give up your cash for a longer period of time. Bonds released at different times will have different interest rates because of what the general 'market rate' for interest was in those periods. ie: if a bond is released in 2016 with interest rates approaching 0%, even a high risk bond would have a lower interest rate than a bond released in the 1980s, when market rates were approaching 20%. Some bonds offer variable interest tied to some market indicator - those will typically have higher interest at the time of issuance, because the bondholder bears some risk that the prevailing market rate will drop. Note regarding sale of bonds after market rates have changed: The value of your bonds will fluctuate with the market. If a bond was offered with 1% interest, and next year interest rates go up and a new identical bond is offered for 2% interest, when you sell your old bond you will take a loss, because the market won't want to pay full price for it anymore. Whether you should sell lower-interest rate bonds depends on how you feel about the factors above - do you want junk bonds that have stock-like levels of returns but high risks of default, maturing in 30 years? Or do you want AAA+ Bonds that have essentially 0% returns maturing in 30 days? If you are paying interest on debt, it is quite likely that you could achieve a net income benefit by selling the bonds, and paying off debt [assuming your debt has a higher interest rate than your low-rate bonds]. Paying off debt is sometimes referred to as a 'zero risk return', because essentially there is no real risk that your lender would otherwise go bankrupt. That is, you will owe your bank the car loan until you pay it, and paying it is the only thing you can do to reduce it. However, some schools of thought suggest that maintaining savings + liquid investments makes sense even if you have some debt, because cash + liquid investments can cover you in some emergencies that credit cards can't help you with. ie: if you lose your job, perhaps your credit could be pulled and you would have nothing except for your liquid savings to tide you over. How much you should save in this way is a matter of opinion, but often repeated numbers are either 3 months or 6 months worth [which is sometimes taken as x months of expenses, and sometimes as x months of after-tax income]. You should look into this issue further; there are many questions on this site that discuss it, I'm sure.",
"title": ""
},
{
"docid": "342485",
"text": "just pick a good bond and invest all your money there (since they're fairly low risk) No. That is basically throwing away your money and why would you do that. And who told you they are low risk. That is a very wrong premise. What factors should I consider in picking a bond and how would they weigh against each other? Quite a number of them to say, assuming these aren't government bonds(US, UK etc) How safe is the institution issuing the bond. Their income, business they are in, their past performance business wise and the bonds issued by them, if any. Check for the bond ratings issued by the rating agencies. Read the prospectus and check for any specific conditions i.e. bonds are callable, bonds can be retired under certain conditions, what happens if they default and what order will you be reimbursed(senior debt take priority). Where are interest rates heading, which will decide the price you are paying for the bond. And also the yield you will derive from the bond. How do you intend to invest the income, coupon, you will derive from the bonds. What is your time horizon to invest in bonds and similarly the bond's life. I have invested in stocks previously but realized that it isn't for me Bonds are much more difficult than equities. Stick to government bonds if you can, but they don't generate much income, considering the low interest rates environment. Now that QE is over you might expect interest rates to rise, but you can only wait. Or go for bonds from stable companies i.e. GE, Walmart. And no I am not saying you buy their bonds in any imaginable way.",
"title": ""
},
{
"docid": "127434",
"text": "You’ve really got three or four questions going here… and it’s clear that a gap in understanding one component of how bonds work (pricing) is having a ripple effect across the other facets of your question. The reality is that everybody’s answers so far touch on various pieces of your general question, but maybe I can help by integrating. So, let’s start by nailing down what your actual questions are: 1. Why do mortgage rates (tend to) increase when the published treasury bond rate increases? I’m going to come back to this, because it requires a lot of building blocks. 2. What’s the math behind a bond yield increasing (price falling?) This gets complicated, fast. Especially when you start talking about selling the bond in the middle of its time period. Many people that trade in bonds use financial calculators, Excel, or pre-calculated tables to simplify or even just approximate the value of a bond. But here’s a simple example that shows the math. Let’s say we’ve got a bond that is issued by… Dell for $10,000. The company will pay it back in 5 years, and it is offering an 8% rate. Interest payments will only be paid annually. Remember that the amount Dell has promised to pay in interest is fixed for the life of the bond, and is called the ‘coupon’ rate. We can think about the way the payouts will be paid in the following table: As I’m sure you know, the value of a bond (its yield) comes from two sources: the interest payments, and the return of the principal. But, if you as an investor paid $14,000 for this bond, you would usually be wrong. You need to ‘discount’ those amounts to take into account the ‘time value of money’. This is why when you are dealing in bonds it is important to know the ‘coupon rate’ (what is Dell paying each period?). But it is also important to know your sellers’/buyers’ own personal discount rates. This will vary from person to person and institution to institution, but it is what actually sets the PRICE you would buy this bond for. There are three general cases for the discount rate (or the MARKET rate). First, where the market rate == the coupon rate. This is known as “par” in bond parlance. Second, where the market rate < the coupon rate. This is known as “premium” in bond parlance. Third, where the market rate > coupon rate. This is known as a ‘discount’ bond. But before we get into those in too much depth, how does discounting work? The idea behind discounting is that you need to account for the idea that a dollar today is not worth the same as a dollar tomorrow. (It’s usually worth ‘more’ tomorrow.) You discount a lump sum, like the return of the principal, differently than you do a series of equal cash flows, like the stream of $800 interest payments. The formula for discounting a lump sum is: Present Value=Future Value* (1/(1+interest rate))^((# of periods)) The formula for discounting a stream of equal payments is: Present Value=(Single Payment)* (〖1-(1+i)〗^((-n))/i) (i = interest rate and n = number of periods) **cite investopedia So let’s look at how this would look in pricing the pretend Dell bond as a par bond. First, we discount the return of the $10,000 principal as (10,000 * (1 / 1.08)^5). That equals $6,807.82. Next we discount the 5 equal payments of $800 as (800* (3.9902)). I just plugged and chugged but you can do that yourself. That equals $3,192.18. You may get slightly different numbers with rounding. So you add the two together, and it says that you would be willing to pay ($6,807.82 + $3,192.18) = $10,000. Surprise! When the bond is a par bond you’re basically being compensated for the time value of money with the interest payments. You purchase the bond at the ‘face value’, which is the principal that will be returned at the end. If you worked through the math for a 6% discount rate on an 8% coupon bond, you would see that it’s “premium”, because you would pay more than the principal that is returned to obtain the bond [10,842.87 vs 10,000]. Similarly, if you work through the math for a 10% discount rate on an 8% coupon bond, it’s a ‘discount’ bond because you will pay less than the principal that is returned for the bond [9,241.84 vs 10,000]. It’s easy to see how an investor could hold our imaginary Dell bond for one year, collect the first interest payment, and then sell the bond on to another investor. The mechanics of the calculations are the same, except that one less interest payment is available, and the principal will be returned one year sooner… so N=4 in both formulae. Still with me? Now that we’re on the same page about how a bond is priced, we can talk about “Yield To Maturity”, which is at the heart of your main question. Bond “yields” like the ones you can access on CNBC or Yahoo!Finance or wherever you may be looking are actually taking the reverse approach to this. In these cases the prices are ‘fixed’ in that the sellers have listed the bonds for sale, and specified the price. Since the coupon values are fixed already by whatever organization issued the bond, the rate of return can be imputed from those values. To do that, you just do a bit of algebra and swap “present value” and “future value” in our two equations. Let’s say that Dell has gone private, had an awesome year, and figured out how to make robot unicorns that do wonderful things for all mankind. You decide that now would be a great time to sell your bond after holding it for one year… and collecting that $800 interest payment. You think you’d like to sell it for $10,500. (Since the principal return is fixed (+10,000); the number of periods is fixed (4); and the interest payments are fixed ($800); but you’ve changed the price... something else has to adjust and that is the discount rate.) It’s kind of tricky to actually use those equations to solve for this by hand… you end up with two equations… one unknown, and set them equal. So, the easiest way to solve for this rate is actually in Excel, using the function =RATE(NPER, PMT, PV, FV). NPER = 4, PMT = 800, PV=-10500, and FV=10000. Hint to make sure that you catch the minus sign in front of the present value… buyer pays now for the positive return of 10,000 in the future. That shows 6.54% as the effective discount rate (or rate of return) for the investor. That is the same thing as the yield to maturity. It specifies the return that a bond investor would see if he or she purchased the bond today and held it to maturity. 3. What factors (in terms of supply and demand) drive changes in the bond market? I hope it’s clear now how the tradeoff works between yields going UP when prices go DOWN, and vice versa. It happens because the COUPON rate, the number of periods, and the return of principal for a bond are fixed. So when someone sells a bond in the middle of its term, the only things that can change are the price and corresponding yield/discount rate. Other commenters… including you… have touched on some of the reasons why the prices go up and down. Generally speaking, it’s because of the basics of supply and demand… higher level of bonds for sale to be purchased by same level of demand will mean prices go down. But it’s not ‘just because interest rates are going up and down’. It has a lot more to do with the expectations for 1) risk, 2) return and 3) future inflation. Sometimes it is action by the Fed, as Joe Taxpayer has pointed out. If they sell a lot of bonds, then the basics of higher supply for a set level of demand imply that the prices should go down. Prices going down on a bond imply that yields will go up. (I really hope that’s clear by now). This is a common monetary lever that the government uses to ‘remove money’ from the system, in that they receive payments from an investor up front when the investor buys the bond from the Fed, and then the Fed gradually return that cash back into the system over time. Sometimes it is due to uncertainty about the future. If investors at large believe that inflation is coming, then bonds become a less attractive investment, as the dollars received for future payments will be less valuable. This could lead to a sell-off in the bond markets, because investors want to cash out their bonds and transfer that capital to something that will preserve their value under inflation. Here again an increase in supply of bonds for sale will lead to decreased prices and higher yields. At the end of the day it is really hard to predict exactly which direction bond markets will be moving, and more importantly WHY. If you figure it out, move to New York or Chicago or London and work as a trader in the bond markets. You’ll make a killing, and if you’d like I will be glad to drive your cars for you. 4. How does the availability of money supply for banks drive changes in other lending rates? When any investment organization forms, it builds its portfolio to try to deliver a set return at the lowest risk possible. As a corollary to that, it tries to deliver the maximum return possible for a given level of risk. When we’re talking about a bank, DumbCoder’s answer is dead on. Banks have various options to choose from, and a 10-year T-bond is broadly seen as one of the least risky investments. Thus, it is a benchmark for other investments. 5. So… now, why do mortgage rates tend to increase when the published treasury bond yield rate increases? The traditional, residential 30-year mortgage is VERY similar to a bond investment. There is a long-term investment horizon, with fixed cash payments over the term of the note. But the principal is returned incrementally during the life of the loan. So, since mortgages are ‘more risky’ than the 10-year treasury bond, they will carry a certain premium that is tied to how much more risky an individual is as a borrower than the US government. And here it is… no one actually directly changes the interest rate on 10-year treasuries. Not even the Fed. The Fed sets a price constraint that it will sell bonds at during its periodic auctions. Buyers bid for those, and the resulting prices imply the yield rate. If the yield rate for current 10-year bonds increases, then banks take it as a sign that everyone in the investment community sees some sign of increased risk in the future. This might be from inflation. This might be from uncertain economic performance. But whatever it is, they operate with some rule of thumb that their 30-year mortgage rate for excellent credit borrowers will be the 10-year plus 1.5% or something. And they publish their rates.",
"title": ""
},
{
"docid": "571181",
"text": "\"How should I allocate short-term assets in a rising-interest rate environment? Assuming that the last part is correct, there could be bear bond funds that short bonds that could work well as a way to invest. However, bear in that the the \"\"rising-interest rate environment\"\" is part of the basis that may or may not be true in the end as I'm not sure I've seen anything to tell me why rates couldn't stay where they are for another couple of years or more. Long-Term Capital Management would be a cautionary tale before about bonds that had assumptions that backfired when something that wasn't supposed to happen, happened. Thus, while you can say there is \"\"rising-interest rate environment\"\" what else are you prepared to assume and how certain are you of that happening? An alternate theory here would be that \"\"junk bonds\"\" may do well because the economy has to be heating up for rates to rise and thus the bonds that are priced down so much because of default risk may turn out to not go bust and thus could do well. Course this would carry the \"\"Your mileage may vary\"\" and without a working time machine I couldn't say which funds will be good and which would suck. As for what I would do if I was dealing with my own money: Money market funds and CDs would likely be my suggestion for the short-term where I want to prevent principal risk. This is likely what I would do if I believed the rising rate environment is here.\"",
"title": ""
},
{
"docid": "510839",
"text": "\"Just to confirm, you don't pay interest when holding a bond, the issuer of the bond pays you interest. The idea of calculating \"\"present value\"\" is as you suggest. You discount future payments using an appropriate rate. These future payments include both the coupon payments you receive through the life of the bond and the principal repayment at the maturity of the bond - each should be discounted from the due date of the payment to today's date. A typical rate to use would be the interest you yourself could earn by investing elsewhere (this gives you some idea of how much it would cost to get those payments another way), or perhaps some standard rate, for example the interbank rates such as LIBOR or FEDFUNDS.\"",
"title": ""
},
{
"docid": "111033",
"text": "\"Bonds are valued based on all of this, using the concept of the \"\"time value of money\"\". Simply stated, money now is worth more than money later, because of what you can do with money between now and later. Case in point: let's say the par value of a bond is $100, and will mature 10 years from this date (these are common terms for most bonds, though the U.S. Treasury has a variety of bonds with varying par values and maturation periods), with a 0% coupon rate (nothing's paid out prior to maturity). If the company or government issuing the bonds needs one million dollars, and the people buying the bonds are expecting a 5% rate of return on their investment, then each bond would only sell for about $62, and the bond issuer would have to sell a par value of $1.62 million in bonds to get its $1m now. These numbers are based on equations that calculate the \"\"future value\"\" of an investment made now, and conversely the \"\"present value\"\" of a future return. Back to that time value of money concept, money now (that you're paying to buy the bond) is worth more than money later (that you'll get back at maturity), so you will expect to be returned more than you invested to account for this time difference. The percentage of rate of return is known as the \"\"yield\"\" or the \"\"discount rate\"\" depending on what you're calculating, what else you take into consideration when defining the rate (like inflation), and whom you talk to. Now, that $1.62m in par value may be hard for the bond issuer to swallow. The issuer is effectively paying interest on interest over the lifetime of the bond. Instead, many issuers choose to issue \"\"coupon bonds\"\", which have a \"\"coupon rate\"\" determining the amount of a \"\"coupon payment\"\". This can be equated pretty closely with you making interest-only payments on a credit card balance; each period in which interest is compounded, you pay the amount of interest that has accrued, to avoid this compounding effect. From an accounting standpoint, the coupon rate lowers the amount of real monies paid; the same $1m in bonds, maturing in 10 years with a 5% expected rate of return, but with a 5% coupon rate, now only requires payments totalling $1.5m, and that half-million in interest is paid $50k at a time annually (or $25k semi-annually). But, from a finance standpoint, because the payments made in the first few years are worth more than the payments made closer to and at maturity, the present value of all these coupon payments (plus the maturity payout) is higher than if the full payout happened at maturity, and so the future value of the total investment is higher. Coupon rates on bonds thus allow a bond issuer to plan a bond package in less complicated terms. If you as a small business need $1m for a project, which you will repay in 10 years, and during that time you are willing to tolerate a 5% interest rate on the outstanding money, then that's exactly how you issue the bonds; $1 million worth, to mature in 10 years and a 5% coupon rate. Now, whether the market is willing to accept that rate is up to the market. Right now, they'd be over the moon with that rate, and would be willing to buy the bonds for more than their face value, because the present value would then match the yield they're willing to accept (as in any market system, you as the seller will sell to the highest bidder to get the best price available). If however, they think you are a bad bet, they'll want an even higher rate of return, and so the present value of all coupon and maturity payments will be less than the par value, and so will the purchase price.\"",
"title": ""
},
{
"docid": "133093",
"text": "How is it possible that long term treasury bonds, which the government has never defaulted on, can hold more risk as an ETF then the stock market index? The risk from long-term bonds isn't that the government defaults, but that interest rates go up before you get paid, so investors want bonds issued more recently at higher interest rates, rather than your older bonds that pay at a lower rate (so the price for your bonds goes down). This is usually caused by higher inflation rates which reduce the value of the interest that you will be paid. Do you assume more risk investing in bond ETFs than you would investing in individual bonds? If you are choosing the right ETFs, there should be a lower amount of risk because the ETFs are taking care of the difficult work of buying a variety of bonds. Are bond ETFs an appropriate investment vehicle for risk diversification? Yes, if you are investing in bonds, exchange traded funds are an appropriate way to buy them. The markets for ETFs are usually very liquid.",
"title": ""
},
{
"docid": "372657",
"text": "\"Let's talk interest rates on your junk bonds. Even after all that the US has been through (and is still going through), the United States dollar is widely regarded as one of the safest safe havens for your money. As such it serves as a de facto baseline against which all other investments can be measured, the bar everyone has to pass: if you could earn 4% on a 5-year US Treasury bond, or earn 4% on anything else over the next 5 years, you pick the Treasury bond. In many ways this means that the interest rate on a Treasury bond is the closest single measure we have to the price of money all by itself. If someone is loaning you money, they could be loaning it to the Treasury instead; they are losing out by making this loan to you, and must charge you at least this rate just to break even. But most people/governments/countries aren't as credit-worthy as the US Treasury. A few are (the US treasury isn't magical, after all, just really good at what it does), but generally they are not. There is a possibility when loaning money to these entities that you will not get your money back. That is risk. All entities have some risk (even the US treasury!), and some have more than others; \"\"junk bonds\"\" have a somewhat elevated level of this risk. Now, you don't just take a risk on for free (unless you're being charitable or something, but I hope you can find better beneficiaries of charity than the average junk bond). You need to be compensated for that risk. Lenders will demand compensation commensurate with that risk - or they will just walk away without making any loans or buying any bonds because it's not worth it. The difference between the interest rate on a US Treasury bond and the interest rate on another bond, such as a junk bond, is the risk premium - the cost of carrying that risk. Therefore you can see that the interest rate on a junk bond is the price of money plus the risk premium. Now, the Federal Reserve adjusts the price of money from time to time, by buying and selling US Treasury bonds until the price is something they like. This means that one component of interest rate on a junk bond is the interest rate on the US Treasury bond, and it is effectively controlled by the Federal Reserve (through that layer of indirection). The other component of the interest rate on a junk bond is the risk premium. It's not generally possible to know in advance whether or not some company will actually default. People have to guess, and decide how comfortable they are taking that risk. This means that risk is more expensive (and interest rates are higher) when they think the companies in question are going through some hard times, and risk will also be more expensive when people decide that they can't take as many risks (perhaps they've already lost some money and need to take additional steps to protect the rest). It's definitely very hard for an individual to decide what the risk on a particular bond is. The good news is that you generally don't have to. There are a bunch of rich jerks, hedge funds, retirement funds, insurance companies, and other investment entities out there who spend all day looking at things like bonds, trying to estimate the risk. Their willingness to exploit minuscule differences between the interest rate on a bond and the real risk means that the average bond on the market will be fairly priced, according to what all those people think. Plenty of them can still be wrong, mind you (cf. mortgage-backed securities) but in the general case the price of any security reflects all the information everyone in the world has on it on average, so if you're wrong you're in good company. When you buy a nice diversified bond fund, you have access to a bunch of bonds at a pretty-standard price. So that's interest rates for you. But you asked about prices. As it turns out, they're the same thing! - just expressed slightly differently. One way or another a bond is essentially meant to be a stream of payments worth a certain amount in the end - this is why you'll hear them referred to sometimes as a \"\"fixed-income security\"\". The interest rate is essentially the difference between the price you pay now, and the value you receive later, except expressed as a rate. Technically, you could structure the bonds differently (e.g. does the bond pay little bits of interest as you go along, or just pay one big lump sum in the end?) but you can use Math to convert between these two situations, and figure out how much money is worth which when, so it doesn't really matter. Anyway. This means that rising interest rates means lower bond prices on bonds you already own (and falling interest rates means higher bond prices). So if the Federal Reserve increases interest rates, the face value of your bond funds will fall. Also, if people think that the companies issuing the bonds are too risky, the face value of those bonds will also fall. (You were probably expecting the latter effect, though.) Mind you, you will still get the same amount of future money out of them as you would otherwise: that's why they're fixed-income securities. However, a higher interest rate means \"\"I can get more money in the future for less money now\"\", and so people will be willing to pay you less for your bond in the present. This is known as interest rate risk. It is higher on longer term bonds, because those have more time to earn interest.\"",
"title": ""
},
{
"docid": "293320",
"text": "The short term bond fund, which you are pretty certain to have as an option, functions in this capacity. Its return will be low, but positive, in all but the most dramatic of rising rate scenarios. I recall a year in the 90's when rates rose enough that the bond fund return was zero or very slightly negative. It's not likely that you'd have access to simple money market or cash option.",
"title": ""
},
{
"docid": "214542",
"text": "\"Even though \"\"when the U.S. sneezes Canada catches a cold\"\", I would suggest considering a look at Canadian government bonds as both a currency hedge, and for the safety of principal — of course, in terms of CAD, not USD. We like to boast that Canada fared relatively better (PDF) during the economic crisis than many other advanced economies, and our government debt is often rated higher than U.S. government debt. That being said, as a Canadian, I am biased. For what it's worth, here's the more general strategy: Recognize that you will be accepting some currency risk (in addition to the sovereign risks) in such an approach. Consistent with your ETF approach, there do exist a class of \"\"international treasury bond\"\" ETFs, holding short-term foreign government bonds, but their holdings won't necessarily match the criteria I laid out – although they'll have wider diversification than if you invested in specific countries separately.\"",
"title": ""
},
{
"docid": "400646",
"text": "\"Can it be so that these low-interest rates cause investors to take greater risk to get a decent return? With interest rates being as low as they are, there is little to no risk in banking; especially after Dodd-Frank. \"\"Risk\"\" is just a fancy word for \"\"Will I make money in the near/ long future.\"\" No one knows what the actual risk is (unless you can see into the future.) But there are ways to mitigate it. So, arguably, the best way to make money is the stock market, not in banking. There is a great misallocation of resources which at some point will show itself and cause tremendous losses, even maybe cause a new financial crisis? A financial crisis is backed on a believed-to-be strong investment that goes belly-up. \"\"Tremendous Losses\"\" is a rather grand term with no merit. Banks are not purposely keeping interest rates low to cause a financial crisis. As the central banks have kept interest rates extremely low for a decade, even negative, this affects how much we save and borrow. The biggest point here is to know one thing: bonds. Bonds affect all things from municipalities, construction, to pensions. If interest rates increased currently, the current rate of bonds would drop vastly and actually cause a financial crisis (in the U.S.) due to millions of older persons relying on bonds as sources of income.\"",
"title": ""
},
{
"docid": "130727",
"text": "\"The answer is yes. And the reason is if today's interest rates are lower than the interest rate (coupon) at which the bond was issued. The bond's \"\"lifetime value\"\" is 100 cents on the dollar. That's the principal repayment that the investor will get on the maturity date. But suppose the bond's coupon rate is 4% while today's interest rate is 3%. Then, people who bought the bond at 100 would get 4% on their money, while everyone else was getting 3%. To compensate, a three year bond would have to rise to almost 103 so that the so-called yield to maturity\"\" would be 3%. Then there would be a \"\"capital loss\"\" (from almost 103 to 100) that would exactly offset the extra interest, that is 1% \"\"more\"\" for three years. If today's interest rates are negative (as they were from time to time in the 1930s, and in the present decade), the \"\"negative\"\" interest rates will prevent the buyer from getting the \"\"lifetime value\"\" (as defined by the OP) of principal plus interest over the original life of the bond. This happens in a \"\"flight to quality\"\" situation, where people are willing to take a (small) capital loss on Treasuries in order to prevent a large possible loss from bank failures like those that took place in 2008.\"",
"title": ""
},
{
"docid": "547982",
"text": "\"**Japan Has Entered The Next Phase: Unlimited Money Printing** Investors have been watching Japan for over a decade now, wondering what happens to a country that has a debt-to-GDP ratio of 234%--too big to realistically pay off. We are starting to get the answer. For review, Japan was the first country in the modern central banking era to begin a policy of quantitative easing--an unconventional form of monetary policy that is used when interest rates have already been lowered to the zero bound. Quantitative easing, which involves the purchase of \"\"printed\"\" money to buy government bonds, was widely viewed in Japan as a failure, but what most people don't understand about Japan's early QE experiments is that they were very small--less than $20 billion a month. It took Prime Minister Shinzo Abe, and BOJ Governor Haruhiko Kuroda to ramp up asset purchases significantly in what was called \"\"Abenomics.\"\" Shinzo Abe, Japan's prime minister. Photographer: Akio Kon/Bloomberg The results of Abenomics have been mixed, but the stock market is certainly higher and the yen is certainly lower, although it's not clear that either of those two developments have really helped. Japan's stock market is mostly foreign-owned, and the weaker yen didn't materially help the balance of trade. Still, there are a lot of people who said that Japan's endless debt deflation would have been worse without Abenomics, so it has remained firmly in place for five years. Abenomics rapidly began to cause distortions, as accelerated asset purchases caused the Bank of Japan to hold a huge percentage of outstanding government bonds, at 40% and rising, as well as being the majority holder of index ETFs. Investors who traffic in JGBs have remarked that the market now functions very poorly, since so much of the market is held by the BOJ. It seems that will get worse, not better. Last year the BOJ implemented a policy of yield curve targeting (ostensibly to help the banks), keeping the overnight rate negative but targeting a 10 year rate at zero percent. The BOJ has been buying longer-dated bonds for years, but this was the first time it ever explicitly capped a rate at longer maturities. Some people wondered how committed the BOJ would be to maintain that cap in the event that JGBs were caught up in a global duration selloff, which we experienced in the last two weeks. As 10-year JGB yields rose above 0.10% last week, the BOJ announced that it was prepared to buy an unlimited amount of bonds to keep yields close to zero percent. As you can imagine, buying an unlimited amount of 10-year JGBs involves printing a theoretically unlimited amount of yen, so the yen weakened significantly on the news. It still remains about ten percent stronger than it was in 2015. We are getting closer to the endgame for Japan. What happens if yields rise further? What happens if the yen depreciates significantly? How much could it depreciate? Could Japan have a currency crisis? What happens if the BOJ ends up owning the entire bond market? These are the questions that investors are asking, and nobody really knows the answers. We are in uncharted territory. I believe that a currency crisis isn't just possible--it's inevitable. And it probably happens at about the time that the BOJ owns all or nearly all of the JGB market, and has to resort to canceling the debt. This sounds like a neat magic trick to make the debt go away, but the laws of economics are not to be conned. Anything is possible--a currency crash, a bond market crash--anything. This is the very definition of debt monetization that resulted in hyperinflation in places like Weimar Germany and Zimbabwe. Is Japan different? We shall see. We will find out soon, as Japan has taken a major step in that direction. Jared Dillian is the author of All the Evil of This World, and the editor of the 10th Man newsletter for Mauldin Economics. Subscribe here. *Forbes articles have 8 tracking cookies and 9 tracking scripts. This comment has none.*(https://www.reddit.com/r/raws/comments/68xk37/about/)\"",
"title": ""
},
{
"docid": "71861",
"text": "Certainly, yes, a zero coupon bond can go down in price. If interest rates rise before your bond matures, the price of the bond will go down – and the longer to maturity, the more it will tend to drop. Depending on when you bought and how much interest rates rise, you can incur a capital loss. The bond is guaranteed to be worth a certain amount at maturity as long as the issuer hasn't defaulted, but before maturity the market price of the bond will fluctuate, primarily based on interest rate movements. In fact, zero coupon bonds are even more interest-rate-sensitive than regular bonds (which have periodic coupon interest payments.)",
"title": ""
},
{
"docid": "551893",
"text": "A stock is an ownership interest in a company. There can be multiple classes of shares, but to simplify, assuming only one class of shares, a company issues some number of shares, let's say 1,000,000 shares and you can buy shares of the company. If you own 1,000 shares in this example, you would own one one-thousandth of the company. Public companies have their shares traded on the open market and the price varies as demand for the stock comes and goes relative to people willing to sell their shares. You typically buy stock in a company because you believe the company is going to prosper into the future and thus the value of its stock should rise in the open market. A bond is an indebted interest in a company. A company issues bonds to borrow money at an interest rate specified in the bond issuance and makes periodic payments of principal and interest. You buy bonds in a company to lend the company money at an interest rate specified in the bond because you believe the company will be able to repay the debt per the terms of the bond. The value of a bond as traded on the open exchange varies as the prevailing interest rates vary. If you buy a bond for $1,000 yielding 5% interest and interest rates go up to 10%, the value of your bond in the open market goes down so that the payment terms of 5% on $1,000 matches hypothetical terms of 10% on a lesser principal amount. Whatever lesser principal amount at the new rate would lead to the same payment terms determines the new market value. Alternatively, if interest rates go down, the current value of your bond increases on the open market to make it appear as if it is yielding a lower rate. Regardless of the market value, the company continues to pay interest on the original debt per its terms, so you can always hold onto a bond and get the original promised interest as long as the company does not go bankrupt. So in summary, bonds tend to be a safer investment that offers less potential return. However, this is not always the case, since if interest rates skyrocket, your bond's value will plummet, although you could just hold onto them and get the low rate originally promised.",
"title": ""
},
{
"docid": "328361",
"text": ">Meanwhile, rivals have fared better. On Aug. 1, Burger King Worldwide Inc. posted its third consecutive quarter of same-store sales growth in the United States and Canada. And on Aug. 7, Wendy’s said its quarterly same-store sales rose more than 3 percent. sounds more like a loss to the competition.",
"title": ""
},
{
"docid": "101580",
"text": "\"The short of it is that bonds are valued based on a fundamental concept of finance called the \"\"time value of money\"\". Stated simply, $100 one year from now is not the same as $100 now. If you had $100 now, you could use it to make more money and have more than $100 in a year. Conversely, if you didn't invest it, the $100 would not buy as much in a year as it would now, and so it would lose real value. Therefore, for these two benefits to be worth the same, the money received a year from now must be more than $100, in the amount of what you could make with $100 if you had it now, or at least the rate of inflation. Or, the amount received now could be less than the amount recieved a year from now, such that if you invested this lesser amount you'd expect to have $100 in a year. The simplest bonds simply pay their face value at maturity, and are sold for less than their face value, the difference being the cost to borrow the cash; \"\"interest\"\". These are called \"\"zero-coupon bonds\"\" and they're around, if maybe uncommon. The price people will pay for these bonds is their \"\"present value\"\", and the difference between the present value and face value determines a \"\"yield\"\"; a rate of return, similar to the interest rate on a CD. Now, zero-coupon bonds are uncommon because they cost a lot. If I buy a zero-coupon bond, I'm basically tying up my money until maturity; I see nothing until the full bond is paid. As such, I would expect the bond issuer to sell me the bond at a rate that makes it worth my while to keep the money tied up. So basically, the bond issuer is paying me compound interest on the loan. The future value of an investment now at a given rate is given by FV = PV(1+r)t. To gain $1 million in new cash today, and pay a 5% yield over 10 years, a company or municipality would have to issue $1.629 million in bonds. You see the effects of the compounding there; the company is paying 5% a year on the principal each year, plus 5% of each 5% already accrued, adding up to an additional 12% of the principal owed as interest. Instead, bond issuers can offer a \"\"coupon bond\"\". A coupon bond has a coupon rate, which is a percentage of the face value of the bond that is paid periodically (often annually, sometimes semi-annually or even quarterly). A coupon rate helps a company in two ways. First, the calculation is very straightforward; if you need a million dollars and are willing to pay 5% over 10 years, then that's exactly how you issue the bonds; $1million worth with a 5% coupon rate and a maturity date 10 years out. A $100 5% coupon bond with a 10-year maturity, if sold at face value, would cost only $150 over its lifetime, making the total cost of capital only 50% of the principal instead of 62%. Now, that sounds like a bad deal; if the company's paying less, then you're getting less, right? Well yes, but you also get money sooner. Remember the fundamental principle here; money now is worth more than money later, because of what you can do with money between now and later. You do realize a lower overall yield from this investment, but you get returns from it quickly which you can turn around and reinvest to make more money. As such, you're usually willing to tolerate a lower rate of return, because of the faster turnaround and thus the higher present value. The \"\"Income Yield %\"\" from your table is also referred to as the \"\"Flat Yield\"\". It is a very crude measure, a simple function of the coupon rate, the current quote price and the face value (R/P * V). For the first bond in your list, the flat yield is (.04/114.63 * 100) = 3.4895%. This is a very simple measure that is roughly analogous to what you would expect to make on the bond if you held it for one year, collected the coupon payment, and then sold the bond for the same price; you'd earn one coupon payment at the end of that year and then recoup the principal. The actual present value calculation for a period of 1 year is PV = FV/(1+r), which rearranges to r = FV/PV - 1; plug in the values (present value 114.63, future value 118.63) and you get exactly the same result. This is crude and inaccurate because in one year, the bond will be a year closer to maturity and will return one less coupon payment; therefore at the same rate of return the present value of the remaining payout of the bond will only be $110.99 (which makes a lot of sense if you think about it; the bond will only pay out $112 if you bought it a year from now, so why would you pay $114 for it?). Another measure, not seen in the list, is the \"\"simple APY\"\". Quite simply, it is the yield that will be realized from all cash flows from the bond (all coupon payments plus the face value of the bond), as if all those cash flows happened at maturity. This is calculated using the future value formula: FV = PV (1+r/n)nt, where FV is the future value (the sum of the face value and all coupon payments to be made before maturity), PV is present value (the current purchase price), r is the annual rate (which we're solving for), n is the number of times interest accrues and/or is paid (for an annual coupon that's 1), and t is the number of years to maturity. For the first bond in the list, the simple APY is 0.2974%. This is the effective compound interest rate you would realize if you bought the bond and then took all the returns and stuffed them in a mattress until maturity. Since nobody does this with investment returns, it's not very useful, but it can be used to compare the yield on a zero-coupon bond to the yield on a coupon bond if you treated both the same way, or to compare a coupon bond to a CD or other compound-interest-bearing account that you planned to buy into and not touch for its lifetime. The Yield to Maturity, which IS seen, is the true yield percentage of the bond in time-valued terms, assuming you buy the bond now, hold it to maturity and all coupon payments are made on time and reinvested at a similar yield. This calculation is based on the simple APY, but takes into account the fact that most of the coupon payments will be made prior to maturity; the present value of these will be higher because they happen sooner. The YTM is calculated by summing the present values of all payments based on when they'll occur; so, you'll get one $4 payment a year from now, then another $4 in two years, then $4 in 3 years, and $104 at maturity. The present value of each of those payments is calculated by flipping around the future value formula: PV = FV/(1+r)t. The present value of the entire bond (its current price) is the sum of the present value of each payment: 114.63 = 4/(1+r) + 4/(1+r)2 + 4/(1+r)3 + 104/(1+r)4. You now have to solve for r, which is difficult to isolate; the easiest way to find the rate with a computer is to \"\"goal seek\"\" (intelligently guess and check). Based on the formula above, I calculated a YTM of .314% for the first bond if you bought on Sept 7, 2012 (and thus missed the upcoming coupon payment). Buying today, you'd also be entitled to about 5 weeks' worth of the coupon payment that is due on Sept 07 2012, which is close enough to the present day that the discounted value is a rounding error, putting the YTM of the bond right at .40%. This is the rate of return you'll get off of your investment if you are able to take all the returns from it, when you receive them, and reinvest them at a similar rate (similar to having a savings account at that rate, or being able to buy fractional shares of a mutual fund giving you that rate).\"",
"title": ""
},
{
"docid": "104160",
"text": "I'll get to my answer in a moment, but first need to put focus on the two key components of bond prices: interest rates and credit risk. Suppose that the 10-year treasury has a coupon of 2% per year (it would be paid as 1% twice per year, in reality). If you own one contract of the bond which we suppose has a so-called face-value of $100, then this contract will over the ten years pay you a total of $20 in coupons, then $100 at redemption. So $120 in total. Would you therefore buy this 10-year treasury bond for $120, or more, or less? Well, if there were bank accounts around which were offering you an interest rate of 2% per year fixed for the next 10 years, then you could alternatively generate $120 from just $100 deposited now (if we assume that the interest paid is not put back in the account to earn 2% per year). Consequently, a price of $100 for the treasury would seem about right. However, suppose that you are not very confident that the banks that offer these accounts will even be around in 10 years time, maybe they will fail before that and you'll never get your money back. Then you might say to yourself that the above calculation is mathematically right, but not really a full representation of the different risks. And you conclude that maybe treasuries should be a bit more expensive, because they offer better credit risk than bank deposits. All of this just to show that the price of bonds is a comparative valuation of rates and credit: you need to know the general level of interest rates available in other investment products (even in stocks, I'd say), you need to have a feel for how much credit risk there is in the different investment products. Most people think that 'normally' interest rates are positive, because we are so familiar with the basic principle that: if I lend you some money then you need to pay me some interest. But in a world where everyone is worried about bank failures, people might prefer to effectively 'deposit' our savings with the US treasury (by buying their bonds) than to deposit their savings in the local bank. The US treasury will see this extra demand and put up the prices of their bonds (they are not stupid at the US treasury, you know!), so maybe the price of the 10-year treasury will go above $120. It could, right? In this scenario, the implied yield on the 10-year treasury is negative. There you go, yields have gone negative because of credit risk concerns.",
"title": ""
},
{
"docid": "561997",
"text": "I think your premise is slightly flawed. Every investment can add or reduce risk, depending on how it's used. If your ordering above is intended to represent the probability you will lose your principal, then it's roughly right, with caveats. If you buy a long-term government bond and interest rates increase while you're holding it, its value will decrease on the secondary markets. If you need/want to sell it before maturity, you may not recover your principal, and if you hold it, you will probably be subject to erosion of value due to inflation (inflation and interest rates are correlated). Over the short-term, the stock market can be very volatile, and you can suffer large paper losses. But over the long-term (decades), the stock market has beaten inflation. But this is true in aggregate, so, if you want to decrease equity risk, you need to invest in a very diversified portfolio (index mutual funds) and hold the portfolio for a long time. With a strategy like this, the stock market is not that risky over time. Derivatives, if used for their original purpose, can actually reduce volatility (and therefore risk) by reducing both the upside and downside of your other investments. For example, if you sell covered calls on your equity investments, you get an income stream as long as the underlying equities have a value that stays below the strike price. The cost to you is that you are forced to sell the equity at the strike price if its value increases above that. The person on the other side of that transaction loses the price of the call if the equity price doesn't go up, but gets a benefit if it does. In the commodity markets, Southwest Airlines used derivatives (options to buy at a fixed price in the future) on fuel to hedge against increases in fuel prices for years. This way, they added predictability to their cost structure and were able to beat the competition when fuel prices rose. Even had fuel prices dropped to zero, their exposure was limited to the pre-negotiated price of the fuel, which they'd already planned for. On the other hand, if you start doing things like selling uncovered calls, you expose yourself to potentially infinite losses, since there are no caps on how high the price of a stock can go. So it's not possible to say that derivatives as a class of investment are risky per se, because they can be used to reduce risk. I would take hedge funds, as a class, out of your list. You can't generally invest in those unless you have quite a lot of money, and they use strategies that vary widely, many of which are quite risky.",
"title": ""
},
{
"docid": "367137",
"text": "Imagine that the existing interest rate is 5%. So on a bond with face value of 100, you would be getting a $5 coupon implying a 5% yield. Now, if let's say the interest rates go up to 10%, then a new bond issued with a face value of 100 will give you a coupon of $10 implying a 10% yield. If someone in the bond market buys your bond after interest price adjustment, in order to make the 10% yield (which means that an investor typically targets at least the risk-free rate on his investments) he needs to buy your bond at $50 so that a $5 coupon can give a 10% yield. The reverse happens when interest rates go down. I hope this somewhat clears the picture. Yield = Coupon/Investment Amount Update: Since the interest rate of the bond does not change after its issuance, the arbitrage in the interest rate is reflected in the market price of the bond. This helps in bringing back the yields of old bonds in-line with the freshly issued bonds.",
"title": ""
},
{
"docid": "565226",
"text": "It depends. Very generally when yields go up stocks go down and when yields go down stocks go up (as has been happening lately). If we look at the yield of the 10 year bond it reflects future expectations for interest rates. If the rate today is very low but expectations are that the short term rates will go up that would be reflected in a higher yield simply because no one would buy the longer term bond if they could simply wait out and get a better return on shoter term investments. If expectations are that the rate is going down you get what's called an inverted yield curve. The inverted yield curve is usually a sign of economic trouble ahead. Yields are also influenced by inflation expectations as @rhaskett is alluding in his answer. So. If the stock market crashes because the economy is doing poorly and if interest rates are relatively high then people would expect the rates to go down and therefore bonds will go up! However, if there's rampant inflation and the rates are going up we can expect stocks and bonds to move in opposite directions. Another interpretation of that is that one would expect stock prices to track inflation pretty well because company revenue is going to go up with inflation. If we're just talking about a bump in the road correction in a healthy economy I wouldn't expect that to have much of an immediate effect though bonds might go down a little bit in the short term but possibly even more in the long term as interest rates eventually head higher. Another scenario is a very low interest rate environment (as today) with a stock market crash and not a lot of room for yields to go further down. Both stocks and bonds are influenced by current interest rates, interest rate expectations, current inflation, inflation expectations and stock price expectation. Add noise and stir.",
"title": ""
},
{
"docid": "211447",
"text": "A falling $AUD would be beneficial to exporters, and thus overall good for the economy. If the economy improves and exporters start growing profits, that means they will start to employ more people and employment will increase - and with higher employment, employees will become more confident to make purchases, including purchasing property. I feel the falling $AUD will be beneficial for the economy and the housing market. However, what you should consider is that with an improving economy and a rising property market, it will only be a matter of time before interest rates start rising. With a lower $AUD the RBA will be more confident in starting to increase interest rates. And increasing interest rates will have a dampening effect on the housing market. You are looking to buy a property to live in - so how long do you intend to live in and hold the property? I would assume at least for the medium to long term. If this is your intention then why are you getting cold feet? What you should be concerned about is that you do not overstretch on your borrowings! Make sure you allow a buffer of 2% to 3% above current interest rates so that if rates do go up you can still afford the repayments. And if you get a fixed rate - then you should allow the buffer in case variable rates are higher when your fixed period is over. Regarding the doomsayers telling you that property prices are going to crash - well they were saying that in 2008, then again in 2010, then again in 2012. I don't know about you but I have seen no crash. Sure when interest rates have gone up property prices have levelled off and maybe gone down by 10% to 15% in some areas, but as soon as interest rates start falling again property prices start increasing again. It's all part of the property cycle. I actually find it is a better time to buy when interest rates are higher and you can negotiate a better bargain and lower price. Then when interest rates start falling you benefit from lower repayments and increasing property prices. The only way there will be a property crash in Australia is if there was a dramatic economic downturn and unemployment rates rose to 10% or higher. But with good economic conditions, an increasing population and low supplies of newly build housing in Australia, I see no dramatic crashes in the foreseeable future. Yes we may get periods of weakness when interest rates increase, with falls up to 15% in some areas, but no crash of 40% plus. As I said above, these periods of weakness actually provide opportunities to buy properties at a bit of a discount. EDIT In your comments you say you intend to buy with a monthly mortgage repayment of $2500 in place of your current monthly rent of $1800. That means your loan amount would be somewhere around $550k to $600K. You also mention you would be taking on a 5 year fixed rate, and look to sell in about 2 years time if you can break even (I assume that is break even on the price you bought at). In 2 years you would have paid $16,800 more on your mortgage than you would have in rent. So here are the facts: A better strategy:",
"title": ""
},
{
"docid": "156477",
"text": "This is pretty basic question, but my head is confused :( If you buy a $1000 bond with 5% interest rate, so it would be $1050 at maturity what does it mean? * you will be paid the interest in coupons (paid in coupons until it totals $50) and at maturity paid $1000 (in one large single payment) * you get paid the full value in coupons ($1050 split by multiple coupons) Any other explanations of how a bond works are welcome, most of the stuff I could find was about what yield is, not how the bond actually works.",
"title": ""
},
{
"docid": "415738",
"text": "In this case the market interest rate is the discount rate that sets equal the market price (current value) of the bond to its present value. To find the market interest rate which is also referred to as promised yield YTM you would have solve for the interest rate in the bond price formula A market price of bond is the sum of discounted coupons and the terminal value of the bond. Most spreadsheet programs and calculators have a RATE function that makes possible finding this market interest rate. First see this for finding a coupon paying bond price The coupon payments are discounted so is the par value of the bond and sum of such discounts is the market price of the bond. The TVM functions in Excel and calculators make this possible using the following equation Let us take your data, 9% $100,000 coupon with 5 years remaining to maturity with market interest rate of 10%. Bonds issued in the US mostly pay two coupons per year. Thus we are finding the present value of 10 coupons each worth $4500 and par value of $100,000. The semi-annual market interest rate is 10%/2 or 5% The negative sign indicate money going out of hand Now solving for RATE is only possible using numerical methods and the RATE function is programmed using Newton-Raphson method to find one of the roots of the bond price equation. This rate will be the periodic rate in this case semi-annual rate which you have to multiply by 2 to get the annual rate. Do remember there is a difference between annual nominal rate and an annualized effective rate. To find the market interest rate If you don't have Excel or a financial calculator then you may opt to use my version of these financial functions in this JavaScript library tadJS",
"title": ""
},
{
"docid": "83381",
"text": "\"Hey guys I have a quick question about a financial accounting problem although I think it's not really an \"\"accounting\"\" problem but just a bond problem. Here it goes GSB Corporation issued semiannual coupon bonds with a face value of $110,000 several years ago. The annual coupon rate is 8%, with two coupons due each year, six months apart. The historical market interest rate was 10% compounded semiannually when GSB Corporation issued the bonds, equal to an effective interest rate of 10.25% [= (1.05 × 1.05) – 1]. GSB Corporation accounts for these bonds using amortized cost measurement based on the historical market interest rate. The current market interest rate at the beginning of the current year on these bonds was 6% compounded semiannually, for an effective interest rate of 6.09% [= (1.03 × 1.03) – 1]. The market interest rate remained at this level throughout the current year. The bonds had a book value of $100,000 at the beginning of the current year. When the firm made the payment at the end of the first six months of the current year, the accountant debited a liability for the exact amount of cash paid. Compute the amount of interest expense on these bonds for the last six months of the life of the bonds, assuming all bonds remain outstanding until the retirement date. My question is why would they give me the effective interest rate for both the historical and current rate? The problem states that the firm accounts for the bond using historical interest which is 10% semiannual and the coupon payments are 4400 twice per year. I was just wondering if I should just do the (Beginning Balance (which is 100000 in this case) x 1.05)-4400=Ending Balance so on and so forth until I get to the 110000 maturity value. I got an answer of 5474.97 and was wondering if that's the correct approach or not.\"",
"title": ""
},
{
"docid": "431953",
"text": "The government pays interest on its debts just like anyone else, but since it's already the government and already taking advantage of credit (your money loaned to it through the bonds), it doesn't need the extra benefit of taxing the interest it pays. **It's better off just issuing bonds at a lower interest rate and letting you keep all the interest, instead of a higher interest rate which will have some amount taxed and returned to it anyway.** The government wants a cut of private loan interest just like any other income, which is why interest on private bonds/loans is taxable. Edit: What about municipal bonds? Wouldn't the federal government benefit from taxing interest on municipal bonds? Municipal bonds are issued to support public infrastructure & services such as construction of water supply infrastructure. Since the goal is to improve facilities for the public benefit, and government programs ostensibly aim to provide public benefits as well, it allows the full proceeds of the bonds to go to the designated projects at the lowest possible interest rate (and the public pays the interest through city rates). Taxing municipal bonds would result in a higher cost to the public for the same end result (because of higher interest rates), with the net interest going to the federal & state governments via income tax on the interest.",
"title": ""
}
] |
7427
|
Equity - date of offer, or date of joining?
|
[
{
"docid": "219470",
"text": "TL;DR: The date they were granted. (Usually, this follows both an offer and acceptance.) It's not uncommon for a new vesting clock to start when there's a new round of funding coming in, because the investors want to make sure the key people are going to be engaged and incentivized going forward from that point. They don't lower their expectations for how long they want folks engaged based on the person having started earlier. Non-institutional investors may have the same concerns as institutional investors here and use the same vesting strategy to address them. Primary recognition of the benefits from having had people start earlier or be there longer (so long as it correlates with having gotten more done) is embedded in the valuation (which affects how much founders' shares are diluted in the raise).",
"title": ""
},
{
"docid": "237783",
"text": "Options or Shares vest by date they are granted. It would strike me as odd for anyone to say their shares were given with 4 year vesting, but the clock was pre-started years prior. In my opinion, you have nothing to complain about.",
"title": ""
}
] |
[
{
"docid": "222577",
"text": "The data for ES_F normally is joined on the contract expiry date, i.e. june is joined to the next month on the expiry date. The discrepancy to the real thing in practice might be significant, as seasonal strategies (as we call these) are mined fairly often.",
"title": ""
},
{
"docid": "394061",
"text": "Humans are born to be naturally communicative. We love our friends who will chat with us. When we join dating websites. Our website is 100% free dating websites can be a lot of fun. Even if you are looking for a serious relationship and housewife sex. It doesn't mean you are desperate about finding the love of your life. Notwithstanding it may be the main purpose of others. People you meet from free dating sites can truly be your companion or friends.",
"title": ""
},
{
"docid": "170481",
"text": "Good credit is calculated (by many lenders) by taking your FICO score which is calculated based upon what is in your credit report. Building credit generally means building up your FICO score. Your FICO score is impacted my many factors, one small one of which is your utilization ratio of your installment loans like student loans. This is the ratio of the current balance to your original balance. To improve your score (slightly) you would want a lower ratio. I would recommend paying your student loan down to 75% ratio as fast as you can and then you can go back to $50/month. A much better way to improve your FICO score is to have revolving credit. Your student loans are not revolving, they are installment loans. Therefore, you should open at least one credit card (assuming you currently have none) right away. The longer you have had a credit card open, the better your FICO score gets. Your revolving credit utilization ratio is way more important than your installment loan ratio. Therefore, to maximize your FICO, try to never have more than 10% utilization on your revolving credit report to the credit bureaus each month. Only the current month's ratio affects your score at any given moment. You can ensure you don't go above 10% by paying your balance before the statement cuts each month to get it below 10% way before any payment would be due. (You should always pay your remaining credit card statement balance in full each month by the due date after the statement cuts to avoid any interest charges.) Note that there is a slight FICO advantage to having at least one major bank credit card instead of just only credit union credit cards. Also, never let all your revolving credit report a zero balance in a month, you must always have at least $1 reporting to the credit bureaus on at least one of your open credit cards or your FICO score will take a big negative hit. If you cannot get a normal credit card, go to a credit union and find one that offers secured credit cards, or a bank that does. A secured credit card is where you place a deposit with the bank that they hold and give you a credit limit to match your security. Ideally it would be a card that graduates to unsecured after your demonstrate good history with them. For example, the Navy Federal Credit Union secured card unsecures for many people. I also believe the Wells Fargo Bank credit card (you can join if there is a family member who served or a roomate who did) also will unsecure. The reason you want it to unsecure and not be forced to open a new account to get an unsecured account is that you want your average age and oldest age of open revolving credit accounts to be as high as possible as this is another impact on your FICO score. Credit unions that anyone can join include, Digital Federal Credit Union, the Pentagon Federal Credit Union (which offers a secured card that does not graduate), and The State Department Federal Credit Union (also offers secured card that I think does not graduate). One other method to boost your FICO score is to get added as an authorized user on one of your parent's credit cards that has been open a long time. Not all lenders will report such an authorized user, however, ones that are known to do so are: Bank of America, Citi Bank, and Capital One. It is a good sign that it will report if they ask for the social security number of the authorized user. However, note that the Authorized User addition can have no impact if the lender is using one of the newer versions of the FICO scoring model, only the older versions reward you for the age of accounts for which you are an authorized user. A very long term boost is to open your first American Express card underwritten directly by Amex such as their Zync card which is pretty easy to get. The advantage of American express is that they remember the date your first credit card was opened with them and if you open new accounts in the future they will back date the date of their opening to match the date your first card was opened. If you let your membership lapse, be sure to record the account number and date opened in your personal files so that you can help them locate it again if you reopen as they can have trouble if it has been on the order of ten years or more. Finally, note that the number of accounts opened in the last twelve months is a small negative mark on your score (along with number of inquiries), so if you open a lot of accounts all at once, in addition to bringing down your average age of accounts, you will also get dinged for how many were opened in the last year.",
"title": ""
},
{
"docid": "379032",
"text": "BATS here means your data feed is coming from BATS only. You're not seeing up to date prices from NASDAQ, NYSE or any other of the ECNs. For a liquid equity like AAPL, BATS prices are typically up to date but for a less liquid listing, you wouldn't always see the NBBO. To get live feeds from every ECN, you have to pay. BATS is offering this information freely and that's why you're seeing it now. AAPL is listed on NASDAQ but you can trade pretty much everything on BATS, just like on other ECNs and exchanges.",
"title": ""
},
{
"docid": "467463",
"text": "Typically the settlement price for a financial instrument (such as AAPL stock) underlying a derivative contract is determined from the average price of trading in that instrument during some short time window specified by the exchange offering the derivative. (Read the fine print on your contract to learn the exact date and time of that settlement period.) Because it's in an exchange's best interest to appear as fair as possible, the exchange will in general pick a high-volume period of time -- such as the close of trading on the expiry date -- in which to determine the settlement price. Now, the expiry date/time may be different from the last time at which the option can be traded, which may be different from the underlying settlement time. For example, most US equity options currently expire on the Saturday following the third Friday of the month, whereas they can last be traded at end-of-day on the third Friday of the month, and the settlement period may be at a slightly different time on the third Friday of the month. (Again, read the contract to know for sure.) Moreover, your broker may demand to know whether you plan to exercise the option at an even earlier date/time. So, to answer your question: After-hours trading can only affect the settlement price of an underlying instrument if the exchange in question decides that the settlement period should happen during after-hours trading. But since no exchange that wants to stay in business would possibly do that, the answer is no. Contract expiry time, contract exercise time, final contract trading time, and underlying settlement time may all fall at different dates/times. The important one for your question is settlement time.",
"title": ""
},
{
"docid": "585282",
"text": "\"I think your confusion comes from the negative impact when a creditor writes off your bad credit and ceases attempting to collect it. \"\"Chargebacks\"\" as you call them are an attempt to undo fraudulent charges on your card, whether from stolen credit card info or from a merchant who is using shady business practices. For what it's worth, if you joined on December 20, January 20 seems like a reasonable date for the next billing cycle, with the December 31 date reflecting the fact that their system couldn't automatically bill you the day you joined. I also think it's reasonable for you to ask them to refund the bill for the second month if you do not plan to use their gym further. So the dispute seems like a reasonable one on both sides. Good luck.\"",
"title": ""
},
{
"docid": "347137",
"text": "\"Here's a very basic MySQL query I put together that does what I want for income/expense report. Basically it reports the same info as the canned income/expense report, but limits it those income/expenses associated with a particular account (rental property, in my case). My main complaint is the output \"\"report\"\" is pretty ugly. And modifying for a different rental property requires changing the code (I could pass parameters etc). Again, the main \"\"issue\"\" in my mind with GnuCash income/expense report is that there is no filter for which account (rental property) you want income/expenses for, unless you set up account tree so that each rental property has its own defined incomes and expenses (i.e. PropertyA:Expense:Utility:electric). Hopefully someone will point me to a more elegant solution that uses the report generator built into GnuCash. THanks! SELECT a2.account_type , a4.name, a3.name, a2.name, SUM(ROUND(IF(a2.account_type='EXPENSE',- s2.value_num,ABS(s2.value_num))/s2.value_denom,2)) AS amt FROM ( SELECT s1.tx_guid FROM gnucash.accounts AS a1 INNER JOIN gnucash.splits AS s1 ON s1.account_guid = a1.guid WHERE a1.name='Property A' ) AS X INNER JOIN gnucash.splits s2 ON x.tx_guid = s2.tx_guid INNER JOIN gnucash.accounts a2 ON a2.guid=s2.account_guid INNER JOIN gnucash.transactions t ON t.guid=s2.tx_guid LEFT JOIN gnucash.accounts a3 ON a3.guid = a2.parent_guid LEFT JOIN gnucash.accounts a4 ON a4.guid = a3.parent_guid WHERE a2.name <> 'Property A' # get all the accounts associated with tx in Property A account (but not the actual Property A Bank duplicate entries. AND t.post_date BETWEEN CAST('2016-01-01' AS DATE) AND CAST('2016-12-31' AS DATE) GROUP BY a2.account_type ,a4.name, a3.name, a2.name WITH ROLLUP ; And here's the output. Hopefully someone has a better suggested approach!\"",
"title": ""
},
{
"docid": "477637",
"text": "Various types of corporate actions will precipitate a price adjustment. In the case of dividends, the cash that will be paid out as a dividend to share holders forms part of a company's equity. Once the company pays a dividend, that cash is no longer part of the company's equity and the share price is adjusted accordingly. For example, if Apple is trading at $101 per share at the close of business on the day prior to going ex-dividend, and a dividend of $1 per share has been declared, then the closing price will be adjusted by $1 to give a closing quote of $100. Although the dividend is not paid out until the dividend pay date, the share price is adjusted at the close of business on the day prior to the ex-dividend date since any new purchases on or after the ex-dividend date are not entitled to receive the dividend distribution, so in effect new purchases are buying on the basis of a reduced equity. It will be the exchange providing the quote that performs the price adjustment, not Google or Yahoo. The exchange will perform the adjustment at the close prior to each ex-dividend date, so when you are looking at historical data you are looking at price data that includes each adjustment.",
"title": ""
},
{
"docid": "333339",
"text": "\"4) Finally, do all companies reduce their stock price when they pay a dividend? Are they required to? There seems to be confusion behind this question. A company does not set the price for their stock, so they can't \"\"reduce\"\" it either. In fact, nobody sets \"\"the price\"\" for a stock. The price you see reported is simply the last price that the stock was traded at. That trade was just one particular trade in a whole sequence of trades. The price used for the trade is simply the price which the particular buyer and particular seller agreed to for that particular trade. (No agreement, well then, no trade.) There's no authority for the price other than the collection of all buyers and sellers. So what happens when Nokia declares a 55 cent dividend? When they declare there is to be a dividend, they state the record date, which is the date which determines who will get the dividend: the owners of the shares on that date are the people who get the dividend payment. The stock exchanges need to account for the payment so that investors know who gets it and who doesn't, so they set the ex dividend date, which is the date on which trades of the stock will first trade without the right to receive the dividend payment. (Ex-dividend is usually about 2 days before record date.) These dates are established well before they occur so all market participants can know exactly when this change in value will occur. When trading on ex dividend day begins, there is no authority to set a \"\"different\"\" price than the previous day's closing price. What happens is that all (knowledgeable) market participants know that today Nokia is trading without the payment 55 cents that buyers the previous day get. So what do they do? They take that into consideration when they make an offer to buy stock, and probably end up offering a price that is about 55 cents less than they would have otherwise. Similarly, sellers know they will be getting that 55 cents, so when they choose a price to offer their stock at, it will likely be about that much less than they would have asked for otherwise.\"",
"title": ""
},
{
"docid": "94259",
"text": "Preparation & processing an application for obtaining Code Number / sub -code number to the newly establishment & Branch office in various part of states for extending the benefit of ESI Scheme to employees employed in that regions. We would process an online application to obtain TIC of newly joined employees within 10 days from the date of joining and data for the same shall be provided by you in time. We would be retrieving the Individual Insurance No.s & maintain their contributions in the devised ESIC Register to be maintained. Monthly Payment Challans to be computed online and same shall be forwarded to you for payment on or before 21st of every month. To ensure payment before due date, data shall be provided in time. Preparation and compilation of Half Yearly Returns and Annual Returns would be our responsibility in cases where manual challan is prepared. All the Payments and Returns would be filed within the stipulated time and the adherence would be monitored by us. Guidelines to the Insured Persons (I.P.) pertaining to the Benefits under the ESIC Act, 1948 and provision of Information related to Insurance Medical Practitioner(Imp's) and Hospitals through ESIC. We would be liasoning on behalf of the establishment with the Regional Office & Branch Office for ensuring smooth functioning. We would also be attending the periodical Inspections and hearings on behalf of the establishment. The Responsibility of the Assessment would be limited for the period which would be coverable under our service tenure. We will keep the Company posted on all Amendments & Development of the Act.",
"title": ""
},
{
"docid": "7208",
"text": "Some other suggestions: Index-tracking mutual funds. These have the same exposure as ETFs, but may have different costs; for example, my investment manager (in the UK) charges a transaction fee on ETFs, but not funds, but caps platform fees on ETFs and not funds! Target date funds. If you are saving for a particular date (often retirement, but could also be buying a house, kids going to college, mid-life crisis motorbike purchase, a luxury cruise to see an eclipse, etc), these will automatically rebalance the investment from risk-tolerant (ie equities) to risk-averse (ie fixed income) as the date approaches. You can get reasonably low fees from Vanguard, and i imagine others. Income funds/ETFs, focusing on stocks which are expected to pay a good dividend. The idea is that a consistent dividend helps smooth out volatility in prices, giving you a more consistent return. Historically, that worked pretty well, but given fees and the current low yields, it might not be smart right now. That said Vanguard Equity Income costs 0.17%, and i think yields 2.73%, which isn't bad.",
"title": ""
},
{
"docid": "238682",
"text": "\"These warrants do not have a fixed expiration date, rather their expiration date is dependant upon the company completing an acquisition. Thirty days after the acquisition is complete the warrants enter their exercise period. The warrants can then be exercised at any time over the next five years. After five years they expire. From the \"\"WARRANT AGREEMENT SOCIAL CAPITAL HEDOSOPHIA HOLDINGS CORP.\"\": A Warrant may be exercised only during the period (the “Exercise Period”) (A) commencing on the later of: (i) the date that is thirty (30) days after the first date on which the Company completes a merger, share exchange, asset acquisition, share purchase, reorganization or similar business combination, involving the Company and one or more businesses (a “Business Combination”), and (ii) the date that is twelve (12) months from the date of the closing of the Offering, and (B) terminating at the earliest to occur of (x) 5:00 p.m., New York City time on the date that is five (5) years after the date on which the Company completes its initial Business Combination, (y) the liquidation of the Company in accordance with the Company’s amended and restated memorandum and articles of association, as amended from time to time, if the Company fails to complete a Business Combination, and (z) 5:00 p.m., New York City time on, other than with respect to the Private Placement Warrants, the Redemption Date (as defined below) as provided in Section 6.2 hereof (the “Expiration Date”); provided, however, that the exercise of any Warrant shall be subject to the satisfaction of any applicable conditions, as set forth in subsection 3.3.2 below, with respect to an effective registration statement Source : lawinsder.com\"",
"title": ""
},
{
"docid": "160787",
"text": "In my experience, any kind of equity you may be offered by the company is just a carrot. Your offer may be written in such a way that your potential ownership represents, say, 1% of the company today. But if the company goes for a round of financing your ownership percentage can get diluted. If this happens a couple of times and the terms of financing aren't very favorable then your percentage can go from that 1% down to 0.001%, making the equity worthless. I've known people who heard their company was being bought and thought they might get some kind of payoff. Come to find out the company hadn't done all that well and there wasn't anything to pay out after the main investors got some money back. (The main investors took a loss.) For obvious reasons, management wasn't keeping the staff up to date about the fact that they were operating in the red and their options were worthless. Some people grumbled about lawyers and filing lawsuits, but at the end of the day, there wasn't any money to be won. Keep this in mind. As to your question regarding what to look out for:",
"title": ""
},
{
"docid": "226984",
"text": "\"The settlement date for any trade is the date on which the seller gets the buyer's money and the buyer gets the seller's product. In US equities markets the settlement date is (almost universally) three trading days after the trade date. This settlement period gives the exchanges, the clearing houses, and the brokers time to figure out how many shares and how many dollars need to actually be moved around in order to give everyone what they're owed (and then to actually do all that moving around). So, \"\"settling\"\" a short trade is the same thing as settling any other trade. It has nothing to do with \"\"closing\"\" (or covering) the seller's short position. Q: Is this referring to when a short is initiated, or closed? A: Initiated. If you initiate a short position by selling borrowed shares on day 1, then settlement occurs on day 4. (Regardless of whether your short position is still open or has been closed.) Q: All open shorts which are still open by the settlement date have to be reported by the due date. A: Not exactly. The requirement is that all short positions evaluated based on their settlement dates (rather than their trade dates) still open on the deadline have to be reported by the due date. You sell short 100 AAPL on day 1. You then cover that short by buying 100 AAPL on day 2. As far as the clearing houses and brokers are concerned, however, you don't even get into the short position until your sell settles at the end of day 4, and you finally get out of your short position (in their eyes) when your buy settles at the end of day 5. So imagine the following scenarios: The NASDAQ deadline happens to be the end of day 2. Since your (FINRA member) broker has been told to report based on settlement date, it would report no open position for you in AAPL even though you executed a trade to sell on day 1. The NASDAQ deadline happens to be the end of day 3. Your sell still has not settled, so there's still no open position to report for you. The NASDAQ deadline happens to be the end of day 4. Your sell has settled but your buy has not, so the broker reports a 100 share open short position for you. The NASDAQ deadline happens to be the end of day 5. Your sell and buy have both settled, so the broker once again has no open position to report for you. So, the point is that when dealing with settlement dates you just pretend the world is 3 days behind where it actually is.\"",
"title": ""
},
{
"docid": "575435",
"text": "The target date investment will automatically reduce equity exposure and increase bond exposure as it approaches retirement date. If you are unlikely to make adjustments as you get older, you may be setting yourself up for more risk down the road. Only you can decide what level of risk you can tolerate as you chase higher gains.",
"title": ""
},
{
"docid": "520286",
"text": "Join one of the largest selections of naughty singles in the UK. Benaughty.com is a website for those seeking a more adventurous dating experience. Browse naughty photos, or chat and flirt online with hot girls and guys. Create a profile for free and start being naughty today.",
"title": ""
},
{
"docid": "61787",
"text": "I think Wikipedia offers a very good explanation: A dividend reinvestment program or dividend reinvestment plan (DRIP) is an equity investment option offered directly from the underlying company. The investor does not receive quarterly dividends directly as cash; instead, the investor's dividends are directly reinvested in the underlying equity. The investor must still pay tax annually on his or her dividend income, whether it is received or reinvested. This allows the investment return from dividends to be immediately invested for the purpose of price appreciation and compounding, without incurring brokerage fees or waiting to accumulate enough cash for a full share of stock. So essentially, a dividend reinvestment plan is offered by companies directly, allowing investors to bypass brokerages, and immediately re-invests dividends rather than paying them out in cash. Investopedia also gives a straighforward definition: A plan offered by a corporation that allows investors to reinvest their cash dividends by purchasing additional shares or fractional shares on the dividend payment date. A DRIP is an excellent way to increase the value of your investment. Most DRIPs allow you to buy shares commission free and at a significant discount to the current share price. Most DRIPS don't allow reinvestments much lower than $10. I had a hard time finding a comprehensive listing of companies that offered DRPs (or DRIPs), but MyDollarPlan.com offers these suggestions: Finding a Dividend Reinvestment Plan: Computershare offers one-stop shopping for hundreds of dividend reinvestment plans. They offer a searchable list that can be filtered to easily find a dividend reinvestment plan that fits your needs. You can also use OneShare. Probably the best way to find out if a company offers a dividend reinvestment plan is to visit the company website. Most companies have an Investor Relations area that will highlight the various options available to shareowners. For example: Coca-Cola, Disney, and Wal-Mart. Hope this helps! @YMCbuzz",
"title": ""
},
{
"docid": "231737",
"text": "The cleanest way to accomplish this is to make the purchase of your new house contingent on the sale of your old one. Your offer should include that contingency and a date by which your house needs to sell to settle the contract. There will also likely be a clause that lets the seller cancel the contract within a period of time (like 24-48 hours) if another offer is received. This gives you (the buyer) at least an opportunity to either sell the house or come up with financing to complete the deal. For example, suppose you make an offer to buy a house for $300,000 contingent on the sale of your house, which the seller accepts. In the meantime, the seller gets an offer of $275,000 in cash (no contingency). The seller has to notify you of the offer and give you some time to make good on your offer, either by selling your house or obtaining $300,000 in financing. If you cannot, the seller can accept the cash offer. This is just a hypothetical example; the offer can have whatever clauses you agree to, but since sale contingencies benefit the buyer, the seller will generally want some compensation for that benefit, e.g. a larger offer or some other clause that benefits them. Or do I find a house to buy first, set a closing date far out and then use that time to sell my current one? Most sellers will not want to set a closing date very far out. Contingency clauses are far more common. In short, yes it's possible, and any competent realtor should be able to handle it. It also may mean that you have to either make a higher offer to compensate for the contingency and to dissuade the seller from entertaining other offers, or sell your home for less than you'd like to get the cash sooner. You can weigh those costs against the cost of financing the new house until yours sells.",
"title": ""
},
{
"docid": "104246",
"text": "Audating Sites is an adult dating website that provides a substantial, sufficient membership to make a game in the action-orientated of personal dating. If you are looking Girls for sex online in the Australia, then we are the best one way for you.Our strategy is to offer simple, fundamental functionality and with actually compiled a significant following of members in the Australia. This is a free online dating website for men and women has quickly garnered the attention of the masses because of it is simple.",
"title": ""
},
{
"docid": "316226",
"text": "Michael Bach Atlanta is the Chief Executive Officer of Drezden Capital Advisors. He was a 16 year veteran in the fund market whereby Michael Bach, Atlanta was earlier the Managing Associate of a mid-market Personal Equity firm. To his credit, Michael Bach Atlanta has applied enterprise takeovers in the health, transportation, submission and different manufacturing disciplines. During his period in the Personal Value industry he started and completed dealings which included debt offerings (Senior and Mezzanine Debt) totaling $189 million, Equity capital assemblages totaling $34 million, as well as executing joining transactions and divestitures totaling $281million during his profession. Mr. Bach joined North Carolina A&T State College in Greensboro, North Carolina, focusing in each Architectural and Mechanical Architectural.",
"title": ""
},
{
"docid": "440103",
"text": "A lot of smaller (and/or weaker) countries did not have much choice when Germany and France decided to rename the German Mark as the Euro, as most of their trade was already in Marks. It was even common for their population to have their savings in Marks. So the question was. Do we wish to have to use the Euro with or without a seat on the board? It was a no brainer for them at the time... The UK has a lot of trade with the USA and other countries outside of the Euro zone, so we are unlikely to have to join the Euro. So in the end it comes down to this point - if the British voters trust a UK government they elected more or less than an EEC government mostly elected by people in the other EEC countries. I don’t think the UK will be joining the Euro anytime soon, but everything can (and will) change with the passage of time. (After all the USA used to be part of the pound trading zone and please can you pay us all the back dated tax you stop paying after a little tea party!) Update: Given what has just happen to Grease and Spain and the Conservative Party has the most seats in the UK parliament, I don’t think the UK will not be joining the Euro for the next 5 years at least",
"title": ""
},
{
"docid": "396184",
"text": "\"Sorry for the late reply. > Different ERP systems have different mappings, but there are no unlimited amount of ERP systems. It's actually close to unlimited. Reasons: 1. Even if two customers use the same ERP system, each implement their ERP in a different way. 2. Even if they implement the ERP system exactly the same way, the EDI is done by an EDI subsystem and each customer will implement EDI in a different way. 3. Even if it's the same EDI system and map, each customer may have different meaning to the same data field. For example, one customer definition for Due Date is \"\"the date the Vendor needs to ship the goods to me\"\" while the other customer says \"\"it's the date I want the goods delivered to my warehouse.\"\" 4. Even if all the fields have the exact same definition, the values may be different between the 2 customers. Classic example: while customer A use SKU# \"\"1234\"\" for a certain widget made by the vendor, the other customer may use SKU# \"\"9876\"\". 5. It's even worse than you think: if say a huge company like Wal-Mart implemented EDI orders in its specific way, Wal-Mart has 100,000 suppliers, so each of those suppliers have to implement the Wal-Mart way of EDI orders. 6. Even worse: when Wal-Mart make a change to their EDI orders (e.g. add a new type of data), 100,000 suppliers have to change their system support the new data requirements. **Do me a favor? I only addresses one statement you made. Can you cut-and-paste your whole message and post it again in /r/edi?** This is the right subreddit for this discussion. You should join it and several people can reply to you... Thanks!\"",
"title": ""
},
{
"docid": "305983",
"text": "According to Active Equity Management by Zhou and Jain: When a stock pays dividend, the adjusted price in Yahoo makes the following adjustment: Let T be the ex-dividend date (the first date that the buyers of a stock will not receive the dividend) and T-1 be the last trading day before T. All prices before T are adjusted by a multiplier (C_{T-1} - d_T)/C_{T-1}, where C_{T-1} is the close price at T-1 and d_T is the dividend per share. This, of course means that the price before T decreases.",
"title": ""
},
{
"docid": "269410",
"text": "It's really boring and you should automate it. Most front office guys worth their salt have built something that will normally calculate what they should have in their portfolios. Basically we own X units of stock K, stock K pays dividend D on date M, you check on date M that we have received X*D for all K's. When trades are made you also need to verify that the dollar amounts are correct, for equity its usually automatic but for fixed income and OTC products you can build a tool to check it.",
"title": ""
},
{
"docid": "394872",
"text": "Yes, Lending Club is the biggest of the bunch, which to date have helped originate $1B of loans. LC just raised more money (bringing total to $100M) and Mary Meeker joined the board. There's a novelty aspect to it b/c it's new but it's just the beginning of parts of the banking industry/process/institutions being disintermediated. Low vol is an easy sell, actually. If investors aren't being paid for risk, why assume it?",
"title": ""
},
{
"docid": "399366",
"text": "If the billing cycle is 2 to 3 months, it would mean Banks have to give credit for a longer period and it makes the entire business less profitable as well as more risky compared to the Monthly billing cycle. For example the current monthly billing cycle with a date say of 14th, means if you swipe your card on 1st day, one would effectively get a credit for 30+14, around 44 days. If you swipe on last day, one would get a credit for 14 days. On an average 22 days of credit. If we make this 3 months, the credit period would increase on an average (90+14)/2, 52 days. From a risk point of view, on monthly cycle if there is non-payment its flagged much earlier compared to a 3 months cycle. On offering different dates, shop around. In the older times the cycles were different, however with individuals having several cards, and trying to optimize every purchase to maximize credit period. Quite a few banks have streamlined it to monthly cycle. Shop around and some banks should be able to offer you different dates.",
"title": ""
},
{
"docid": "324661",
"text": "\"Making these difficult portfolio decisions for you is the point of Target-Date Retirement Funds. You pick a date at which you're going to start needing to withdraw the money, and the company managing the fund slowly turns down the aggressiveness of the fund as the target date approaches. Typically you would pick the target date to be around, say, your 65th birthday. Many mutual fund companies offer a variety of funds to suit your needs. Your desire to never \"\"have to recover\"\" indicates that you have not yet done quite enough reading on the subject of investing. (Or possibly that your sources have been misleading you.) A basic understanding of investing includes the knowledge that markets go up and down, and that no portfolio will always go up. Some \"\"recovery\"\" will always be necessary; having a less aggressive portfolio will never shield you completely from losing money, it just makes loss less likely. The important thing is to only invest money that you can afford to lose in the short-term (with the understanding that you'll make it back in the long term). Money that you'll need in the short-term should be kept in the absolute safest investment vehicles, such as a savings account, a money market account, short-term certificates of deposit, or short-term US government bonds.\"",
"title": ""
},
{
"docid": "151871",
"text": "\"Their is no arbitrage opportunity with \"\"buying dividends.\"\" You're buying a taxable event. This is a largely misunderstood topic. The stock always drops by the amount if the dividend on the ex date. The stock opens that day trading \"\"ex\"\" (excluding) the dividend. It then pays out later based in the shareholders on record. There is a lot of talk about price movement and value here. That can happen but it's from trading not from the dividend per se. Yes sometimes you do see a stock pop the day prior to ex date because people are buying the stock for the dividend but the trading aspect of a stock is determined by supply and demand from people trading the stock. The dividends are paid out from the owners equity section of the balance sheet. This is a return of equity to shareholders. The idea is to give owners of the company some of their investment back (from when they bought the stock) without having the owners sell the shares of the company. After all if it's a good company you want to keep holding it so it will appreciate. Another similar way to think of it is like a bonds interest payment. People sometimes forget when trading that these are actual companies meant to be invested in. Your buying an ownership in the company with your cash. It really makes no difference to buy the dividend or not, all other things constant. Though market activity can add or lose value from trading as normal.\"",
"title": ""
},
{
"docid": "405166",
"text": "\"Total Capital This is a very old fashioned term that really is mostly only used in the finance industry today, like when everyone was obsessed with \"\"bank capital\"\". Total Capital = Preferred Equity + Common Equity + Liabilities True blue preferred shares are almost only used by financial companies, banks specifically. The more modern ones that convert to common are used by all other companies. Notes Payable This is another old fashioned term that now carries a different meaning in Generally Accepted Account Principles (GAAP). The oldest definition of a note or a promissory note is a promise to pay a fixed amount of money on a specific date. This has been modified to resemble more a bond and evolved into the zero coupon bond, a bond that makes no cash interest payments but makes one final payment that includes principal & interest. A bank note, like a One Dollar bill, is a note that pays something, in this case One Dollar, never (technically, the repayment date is simply not specified in the contract). While it pays One Dollar, it never pays it back, so it has a constant value of One Dollar. The constant nature, inflation notwithstanding, is what makes bank notes the preferred medium of exchange. GAAP has taken its' own definition to mean any debt payable within 12 months, as it is a current (<12 months) liability.\"",
"title": ""
},
{
"docid": "560251",
"text": "I don't believe Saturday is a business day either. When I deposit a check at a bank's drive-in after 4pm Friday, the receipt tells me it will credit as if I deposited on Monday. If a business' computer doesn't adjust their billing to have a weekday due date, they are supposed to accept the payment on the next business day, else, as you discovered, a Sunday due date is really the prior Friday. In which case they may be running afoul of the rules that require X number of days from the time they mail a bill to the time it's due. The flip side to all of this, is to pick and choose your battles in life. Just pay the bill 2 days early. The interest on a few hundred dollars is a few cents per week. You save that by not using a stamp, just charge it on their site on the Friday. Keep in mind, you can be right, but their computer still dings you. So you call and spend your valuable time when ever the due date is over a weekend, getting an agent to reverse the late fee. The cost of 'right' is wasting ten minutes, which is worth far more than just avoiding the issue altogether. But - if you are in the US (you didn't give your country), we have regulations for everything. HR 627, aka The CARD act of 2009, offers - ‘‘(2) WEEKEND OR HOLIDAY DUE DATES.—If the payment due date for a credit card account under an open end consumer credit plan is a day on which the creditor does not receive or accept payments by mail (including weekends and holidays), the creditor may not treat a payment received on the next business day as late for any purpose.’’. So, if you really want to pursue this, you have the power of our illustrious congress on your side.",
"title": ""
}
] |
3140
|
What is the cost of “free” trades?
|
[
{
"docid": "174310",
"text": "\"In the case of Wells Fargo, I believe that free trading is linked to your overall banking relationship with the firm. So if you have a checking account with a balance of $X, or a total relationship with the bank (\"\"relationship\"\" is usually defined as loan balances + deposit balances) over a certain amount, they give you a plum like free stock trades. The theory behind this approach is that banks want to be a one-stop shop for you. The idea is that they can market the banks products to you over a period of years (lowering customer acquisition cost) and offer you a level of convenience that allows them to charge a premium for services. For example, many people will pay a rate or fee premium on a mortgage or car loan so that they can do all of their business in one place. In other cases, free trading is linked to marketing campaigns by funds. Charles Schwab started this with the \"\"no transaction fee\"\" mutual fund store many years ago -- transaction fees are actually paid for by the mutual funds who pay for placement in the program. \"\"Free ETF trade\"\" programs are similar.\"",
"title": ""
}
] |
[
{
"docid": "179520",
"text": "Your question is unanswerable as you haven't provided enough information. I.e. If those shares cost $1000 and you have $50000 ( or any number above $1000) of cash available in the account then you can't possibly free ride. I think your understanding of the free ride rule is incorrect. Basically what this rule is stating is that you have to have the cash when the trade is placed in order to settle the trade. Otherwise you are taking on margin (which you can't do in a cash account). So at order entry you have to have the cash to cover the purchase so it's able to be settled. If you do, no problem and you can sell that stock before trade settlement. There is no law that says you have to hold it past trade settlement. However, you cannot spend the same dollar more than once before it settles. This site does a good job explaining this more throughly with examples: http://www.invest-faq.com/articles/trade-day-free-ride.html",
"title": ""
},
{
"docid": "254910",
"text": "Note, the main trade off here is the costs of holding cash rather than being invested for a few months vs trading costs from trading every month. Let's start by understanding investing every month vs every three months. First compare holding cash for two months (at ~0% for most Canadians right now) and then investing on the third month vs being invested in a single stock etf (~5% annually?). At those rates she is forgoing equity returns of around These costs and the $10 for one big trade give total costs of $16+$8+$10=$34 dollars. If you were to trade every month instead there would be no cost for not being invested and the trading costs over three months would just be 3*$10=$30. So in this case it would be better to trade monthly instead of every three months. However, I'm guessing you don't trade all $2000 into a single etf. The more etfs you trade the more trading more infrequently would be an advantage. You can redo the above calculations spliting the amount across more etfs and including the added trading costs to get a feel for what is best. You can also rotate as @Jason suggests but that can leave you unbalanced temporarily if not done carefully. A second option would be to find a discount broker that allows you to trade the etfs you are interested in for free. This is not always possible but often will be for those investing in index funds. For instance I trade every month and have no brokerage costs. Dollar cost averaging and value averaging are for people investing a single large amount instead of regular monthly amounts. Unless the initial amount is much much larger than the monthly amounts this is probably not worth considering. Edit: Hopefully the above edits will clarify that I was comparing the costs (including the forgone returns) of trading every 3 months vs trading every month.",
"title": ""
},
{
"docid": "322725",
"text": "In the past 10 years there have been mutual funds that would act as a single bucket of stocks and bonds. A good example is Fidelity's Four In One. The trade off was a management fee for the fund in exchange for having to manage the portfolio itself and pay separate commissions and fees. These days though it is very simple and pretty cheap to put together a basket of 5-6 ETFs that would represent a balanced portfolio. Whats even more interesting is that large online brokerage houses are starting to offer commission free trading of a number of ETFs, as long as they are not day traded and are held for a period similar to NTF mutual funds. I think you could easily put together a basket of 5-6 ETFs to trade on Fidelity or TD Ameritrade commission free, and one that would represent a nice diversified portfolio. The main advantage is that you are not giving money to the fund manager but rather paying the minimal cost of investing in an index ETF. Overall this can save you an extra .5-1% annually on your portfolio, just in fees. Here are links to commission free ETF trading on Fidelity and TD Ameritrade.",
"title": ""
},
{
"docid": "30959",
"text": "\"Disclosure: I don't have an iPhone, so I don't use RobinHood. That being said, I have a less \"\"they're-out-to-get-ya\"\" view of what they're doing. As a small business owner (2 businesses), employees cost the most. If you can create a solid business with few (or no) employees and let robots run it, you will drastically reduce your costs. Joe Polish said it similarly with sales letters, something along the lines of they never complain about a headache, need to take a year off to discover themself, or just need a personal day. Robots are the same; they do not have human limits. Most simple trading can be done and maintained by well written code and AI, there's very little need for humans to do anything other than build it. Think about the efficiency of bitcoin versus all the central banks combined; how many people are employed by central banks? Robinhood states that they are using technology in these ways to minimize costs and they're using a system that doesn't need physical branches (this doesn't mean they will never have them, just that they don't need them). Robinhood does not indicate that they allow everything to happen for free; only stock trading. I worked for a large trading firm once and observed that stock trading wasn't the bulk of where they made their money anyway; trading options, futures, index funds, etc are where the big money was and Robinhood says nothing about those being free. Like the CQM mentioned too, they'll be charging for margin as well. In a way, the individual stock trader is dead; many people - including this forum - prefer index funds, so more than likely, Robinhood will strike up a deal with an index fund company or create their own (this is just easy, passive income with an expense ratio). In this category, the markets are their playground, but they do need to attract enough people to their platform, thus free stock trading is a good way to do it. As for selling your information for advertising, that is always a possibility, but they have quite a few other options that would be good for most investors (index funds, affiliating with financial fund companies, etc) where they can start before ever needing to dip their toe in selling information. This isn't to say they won't do it, but that there are few other options they have. The major concern I have for Robinhood is ongoing security. Just building it and letting it run kind of assumes that there won't be major compromises in the future and as AI evolves, superior AI might be able to crush older AI.\"",
"title": ""
},
{
"docid": "44578",
"text": "\"I use TIAA-Cref for my 403(b) and Fidelity for my solo 401(k) and IRAs. I have previously used Vanguard and have also used other discount brokers for my IRA. All of these companies will charge you nothing for an IRA, so there's really no point in comparing cost in that respect. They are all the \"\"cheapest\"\" in this respect. Each one will allow you to purchase their mutual funds and those of their partners for free. They will charge you some kind of fee to invest in mutual funds of their competitors (like $35 or something). So the real question is this: which of these institutions offers the best mutual and index funds. While they are not the worst out there, you will find that TIAA-Cref are dominated by both Vanguard and Fidelity. The latter two offer far more and larger funds and their funds will always have lower expense ratios than their TIAA-Cref equivalent. If I could take my money out of TIAA-Cref and put it in Fidelity, I'd do so right now. BTW, you may or may not want to buy individual stocks or ETFs in your account. Vanguard will let you trade their ETFs for free, and they have lots. For other ETFs and stocks you will pay $7 or so (depends on your account size). Fidelity will give you free trades in the many iShares ETFs and charge you $5 for other trades. TIAA-Cref will not give you any free ETFs and will charge you $8 per trade. Each of these will give you investment advice for free, but that's about what it's worth as well. The quality of the advice will depend on who picks up the phone, not which institution you use. I would not make a decision based on this.\"",
"title": ""
},
{
"docid": "583062",
"text": "\"Emotion aside, you can calculate the cost of the funds you have tied up at the bank. If I can earn 5% in a CD, my \"\"free\"\" checking with minimum $5000 balance really costs me $250/yr. You have money tied up, I understand, but where would you place it otherwise, and at what return? The subject of frequent trading even at zero cost is worth addressing, but not the real subject of your question. So, I'll leave it for elsewhere.\"",
"title": ""
},
{
"docid": "550319",
"text": "This depends on a lot actually - with the overall being your goals and how much you like risk. Question: What are your fees/commissions for selling? $8.95/trade will wipe out some gains on those trades. (.69% if all are sold with $8.95 commission - not including the commission payed when purchased that should be factored into the cost basis) Also, I would recommend doing commission free ETFs. You can get the same affect as a mutual fund without the fees associated with paying someone to invest in ETFs and stocks. On another note: Your portfolio looks rather risky. Although everyone has their own risk preference so this might be yours but if you are thinking about a mutual fund instead of individual stocks you probably are risk averse. I would suggest consulting with an adviser on how to set up for the future. Financial advice is free flowing from your local barber, dentist, and of course StackExchange but I would look towards a professional. Disclaimer: These are my thoughts and opinions only ;) Feel free to add comments below.",
"title": ""
},
{
"docid": "323768",
"text": "\"(See also the question How many stocks I can exercise per stock warrant? and my comments there). Clearly, at the prices you quote, it does not seem sensible to exercise your warrants at the moment, since you can still by \"\"units\"\" (1 stock + 1/3 warrant) and bare stock at below the $11.50 it would cost you to exercise your warrant. So when would exercising a warrant become \"\"a sensible thing to do\"\"? Obviously, if the price of the bare stock (which you say is currently $10.12) were to sufficiently exceed $11.50, then it would clearly be worth exercising a warrant and immediately selling the stock you receive (\"\"sufficiently exceed\"\" to account for any dealing costs in selling the newly-acquired stock). However, looking more closely, $11.50 isn't the correct \"\"cut-off\"\" price. Consider three of the units you bought at $10.26 each. For $30.78 you received three shares of stock and one warrant. For an additional $11.50 ($42.28 in total) you can have a total of four shares of stock (at the equivalent of $10.57 each). So, if the price of the bare stock rises above $10.57, then it could become sensible to exercise one warrant and sell four shares of stock (again allowing a margin for the cost of selling the stock). The trading price of the original unit (1 stock + 1/3 warrant) shouldn't (I believe) directly affect your decision to exercise warrants, although it would be a factor in deciding whether to resell the units you've already got. As you say, if they are now trading at $10.72, then having bought them at $10.26 you would make a profit if sold. Curiously, unless I'm missing something, or the figures you quote are incorrect, the current price of the \"\"unit\"\" (1 stock + 1/3 warrant; $10.72) seems overpriced compared to the price of the bare stock ($10.12). Reversing the above calculation, if bare stock is trading at $10.12, then four shares would cost $40.48. Deducting the $11.50 cost-of-exercising, this would value three \"\"combined units\"\" at $28.98, or $9.66 each, which is considerably below the market price you quote. One reason the \"\"unit\"\" (1 stock + 1/3 warrant) is trading at $10.72 instead of $9.66 could be that the market believes the price of the bare share (currently $10.12) will eventually move towards or above $11.50. If that happens, the option of exercising warrants at $11.50 becomes more and more attractive. The premium presumably reflects this potential future benefit. Finally, \"\"Surely I am misunderstand the stock IPO's intent.\"\": presumably, the main intent of Social Capital was to raise as much money as possible through this IPO to fund their future activities. The \"\"positive view\"\" is that they expect this future activity to be profitable, and therefore the price of ordinary stock to go up (at least as far as, ideally way beyond) the $11.50 exercise price, and the offering of warrants will be seen as a \"\"thank you\"\" to those investors who took the risk of taking part in the IPO. A completely cynical view would be that they don't really care what happens to the stock price, but that \"\"offering free stuff\"\" (or what looks like \"\"free stuff\"\") will simply attract more \"\"punters\"\" to the IPO. In reality, the truth is probably somewhere between those two extremes.\"",
"title": ""
},
{
"docid": "592671",
"text": "Your dislike for free trade scares me. Shopping for lower wagers in order to bring production cost down is extremely beneficial to both the surrounding production area and the receiving consumers of the products. If it isn't beneficial then the company loses demand and eventually fails. I believe where you hatred stems from is fiat currency and foreign affairs. Free market has its con-men and hustlers but that is far better than government control. You decide what you spend your money in and no one else can say otherwise.",
"title": ""
},
{
"docid": "233635",
"text": "\"As proposed: Buy 100 oz of gold at $1240 spot = -$124,000 Sell 1 Aug 2014 Future for $1256 = $125,600 Profit $1,600 Alternative Risk-Free Investment: 1 year CD @ 1% would earn $1240 on $124,000 investment. Rate from ads on www.bankrate.com \"\"Real\"\" Profit All you are really being paid for this trade is the difference between the profit $1,600 and the opportunity for $1240 in risk free earnings. That's only $360 or around 0.3%/year. Pitfalls of trying to do this: Many retail futures brokers are set up for speculative traders and do not want to deal with customers selling contracts against delivery, or buying for delivery. If you are a trader you have to keep margin money on deposit. This can be a T-note at some brokerages, but currently T-notes pay almost 0%. If the price of gold rises and you are short a future in gold, then you need to deposit more margin money. If gold went back up to $1500/oz, that could be $24,400. If you need to borrow this money, the interest will eat into a very slim profit margin over the risk free rate. Since you can't deliver, the trades have to be reversed. Although futures trades have cheap commissions ~$5/trade, the bid/ask spread, even at 1 grid, is not so minimal. Also there is often noisy jitter in the price. The spot market in physical gold may have a higher bid/ask spread. You might be able to eliminate some of these issues by trading as a hedger or for delivery. Good luck finding a broker to let you do this... but the issue here for gold is that you'd need to trade in depository receipts for gold that is acceptable for delivery, instead of trading physical gold. To deliver physical gold it would likely have to be tested and certified, which costs money. By the time you've researched this, you'll either discover some more costs associated with it or could have spent your time making more money elsewhere.\"",
"title": ""
},
{
"docid": "162616",
"text": "No free lunch You cannot receive risk-free interest on more money than you actually put down. The construct you are proposing is called 'Carry Trade', and will yield you the interest-difference in exchange for assuming currency risk. Negative expectation In the long run one would expect the higher-yielding currency to devalue faster, at a rate that exactly negates the difference in interest. Net profit is therefore zero in the long run. Now factor in the premium that a (forex) broker charges, and now you may expect losses the size of which depends on the leverage chosen. If there was any way that this could reliably produce a profit even without friction (i.e. roll-over, transaction costs, spread), quants would have already arbitraged it away. Intransparancy Additionaly, in my experience true long-term roll-over costs in relation to interest are a lot harder to compute than, for example, the cost of a stock transaction. This makes the whole deal very intransparant. As to the idea of artificially constructing a USD/USD pair: I regret to tell you that such a construct is not possible. For further info, see this question on Carry Trade: Why does Currency Carry Trade work?",
"title": ""
},
{
"docid": "400196",
"text": "Almost all major no-load mutual fund families allow you to do the kind of thing you are talking about, however you may need an initial investment of between $1000 to $3000 depending on the fund. Once you have it however, annual fee's are usually very little, and the fees to buy that companies funds are usually zero if it's a no-load company (Vanguard, TRowPrice, etc) With the larger companies that means you have a pretty large selection of funds, but generally EACH fund has a minimum initial purchase, once that's met then you can buy additional amounts in small quantities without a problem. For someone on a smaller budget, many low cost brokers (ETrade as mentioned by Litteadv, Scottrade as mentioned by myself in another similar question today) allow you to start with smaller initial balances and have a small selection of funds or ETF's that you can trade from without commission. In the case of Scottrade, they have like 15 ETF's that you can trade comission free. Check with the various low cost brokerages such as ETrade, Scottrade, and TDAmeritrade, to see what their policies are, and what if any funds/ETF's they allow you to trade in without commissions. Keep in mind that for Mutual funds, there may still be a fund minimum initial investment that applies, be sure to check if that is the case or not. The lack of any minimum investment makes ETF's a slightly more attractive option for someone who doesn't have the 'buy in' that many funds require.",
"title": ""
},
{
"docid": "588165",
"text": "The issue I have with your use of Japan is that Japan has very strong exports of superior quality and low cost, we do not. And what about South and Central American Pesos? What about Keynes, Minsky, and the trilemma? Their central banks were completely overridden by foreign speculators. We can only choose two out of three options, peg our currency, spend to help the economy, and/or maintain free trade, not all three",
"title": ""
},
{
"docid": "310112",
"text": "\"The first consideration for the banking part of your portfolio is safety. In the United States that is FDIC protection, or the equivalent for a Credit Union. The second consideration is does it have the level of service you need. For this I mean the location of branches, ATMs, or its online services meet your needs for speed, accuracy, and ability to access or move the money as you need. The rest are then balanced on the extras. For your situation those extras include the ability to make free trades. For other it might be a discount on their mortgage. For others it is free checking. In your current situation if the first two things are met, and you are using those extra benefits then don't change. For me the free trades wouldn't be a benefit, so any major degradation in the safety and service would cause me to leave. Keep in mind that free services exist to entice you to make a deposit: which they can then make money by lending it out; or they offer a free service to entice you to use a service they can charge you to use. All Free services come with a cost. I earned a completely paltry $3.33 YTD over the last 9 months on my savings at my bank presumably in exchange for these \"\"free\"\" trades. Without knowing how much you had deposited in your savings account there is no way to know how much you could have made at the bank across the street. But with the low rates of the last decade there is not big money to be made off the emergency savings of a typical american family.\"",
"title": ""
},
{
"docid": "93836",
"text": "\"Because ETFs, unlike most other pooled investments, can be easily shorted, it is possible for institutional investors to take an arbitrage position that is long the underlying securities and short the ETF. The result is that in a well functioning market (where ETF prices are what they should be) these institutional investors would earn a risk-free profit equal to the fee amount. How much is this amount, though? ETFs exist in a very competitive market. Not only do they compete with each other, but with index and mutual funds and with the possibility of constructing one's own portfolio of the underlying. ETF investors are very cost-conscious. As a result, ETF fees just barely cover their costs. Typically, ETF providers do not even do their own trading. They issue new shares only in exchange for a bundle of the underlying securities, so they have almost no costs. In order for an institutional investor to make money with the arbitrage you describe, they would need to be able to carry it out for less than the fees earned by the ETF. Unlike the ETF provider, these investors face borrowing and other shorting costs and limitations. As a result it is not profitable for them to attempt this. Note that even if they had no costs, their maximum upside would be a few basis points per year. Lots of low-risk investments do better than that. I'd also like to address your question about what would happen if there was an ETF with exorbitant fees. Two things about your suggested outcome are incorrect. If short sellers bid the price down significantly, then the shares would be cheap relative to their stream of future dividends and investors would again buy them. In a well-functioning market, you can't bid the price of something that clearly is backed by valuable underlying assets down to near zero, as you suggest in your question. Notice that there are limitations to short selling. The more shares are short-sold, the more difficult it is to locate share to borrow for this purpose. At first brokers start charging additional fees. As borrowable shares become harder to find, they require that you obtain a \"\"locate,\"\" which takes time and costs money. Finally they will not allow you to short at all. Unlimited short selling is not possible. If there was an ETF that charged exorbitant fees, it would fail, but not because of short sellers. There is an even easier arbitrage strategy: Investors would buy the shares of the ETF (which would be cheaper than the value of the underlying because of the fees) and trade them back to the ETF provider in exchange for shares of the underlying. This would drain down the underlying asset pool until it was empty. In fact, it is this mechanism (the ability to trade ETF shares for shares of the underlying and vice versa) that keeps ETF prices fair (within a small tolerance) relative to the underlying indices.\"",
"title": ""
},
{
"docid": "541054",
"text": "Keep it simple: mutual funds (preferably index, low fee or ETF linked funds) do make a nice start for your little princess college fund. You dont need a real fortune to offset the trading cost of an online broker but if your really going to take advantage of dollar cost averaging, you might want to invest into a trusted fund company. Do your research, it is worth it. Ignore what the investment salesman is saying, he works for his wealth, not yours. A good DIY strategy, either joint with your own retirement account agregate or on a low cost index fund will make wonders. Keep in mind to be resilient: you will cash out when the princess will be in college in 20 yerars. Make sure to make proper time horizon investment and allocation. Cheers, All the best. Feel free to edit",
"title": ""
},
{
"docid": "132034",
"text": "\"And what's wrong with lower cost? What makes you entitled to higher wage when someone can do it for lower cost? Why do you like eating like a king in from pre industrial era? Why do you not like paying fortune for bacons? Call it use or abuse. That's how it always have worked and made capitalism so successful. I didn't claim \"\"in ideal economy\"\". I said in competitive market. There are many industries that are competitive. Many of them have shown that outsourcing portion of IT is the right move. Even Cloud platform such as Azure and AWS are replacement of some IT work traditionally done. Free trade of goods and services(barring externalities and risks) are econ 101. If you don't get it, I suggest you take up a reading on Ricardian Theory. Honestly, I was lucky to have a good professor go over it with me.\"",
"title": ""
},
{
"docid": "387194",
"text": ">IOW, everyone is perfectly free to instantaneously decide that a dollar is worth only 1/1,000,000,000th of an orange, and oranges would instantly cost a billion dollars. Oranges cost less than that not because the government sets the price of oranges, but purely because that's what the market agrees to. This shows a profound misunderstanding of how fiat currencies work. The demand for fiat currencies comes from the fact they are necessary to pay taxes and debts. Other currencies/commodities will not be recognized as settlement of debts in court disputes, so they would first need to be sold onto the market in exchange for the fiat currency. Individuals can't simply *decide* what the relative value of certain goods and services are. The market does that, collectively via voluntary trade. >I'm explaining internal combustion for a 5-year-old, and you're calling it inaccurate and misleading because it doesn't address the sociological implications of American car-culture. Hahah, you're confusing the oil for the gasoline!",
"title": ""
},
{
"docid": "82360",
"text": "I don't know if all these facts can be attributed to NAFTA but it is hard to escape the feeling that trade agreements hurt US workers. I have no doubt that a companies bottom line benefits from free trade and that consumers get access to cheaper goods- but the well being of the nation as a whole is not necessarily the same as the financial well being of corporations or lower prices for junk. Free trade agreements, without a doubt, have hurt average workers. Whenever economics is discussed it is important to keep in mind that the most economists are valuing these kinds of deals in ways that don't make sense to the average person. No one, for instance, can place a value on the person who lost their job- or how that impacts their family and community. I understand why- those kinds of social costs cannot be measured.",
"title": ""
},
{
"docid": "492981",
"text": "You did not answer my question. Is it moral to steal from me to pay off someone else's debt because I payed mine off? Is that moral? Why is college the only option to learning skills? What about online learning or trade skills? There is a reason coding boot camps are popping up everywhere. Tuition is skyrocketing because universities have no incentives to cut costs/prices because the Government hands out free tuition/low interest rate loans.",
"title": ""
},
{
"docid": "386796",
"text": "I have had accounts at both IB and Questrade. Whatever you've heard about Questrade, sadly much of it is true pertaining to 2007-2009. I have not had any issues with their service, and making the few trades I do with the QuestraderWEB service has been flawless. In the time that I've had the account, their service has constantly been improving (statements are easier to read, customer service is more responsive). You should read what FrugalTrader and Canadian Capitalist have to say along with the combined 1000+ comments before deciding. Interactive Brokers is a whole different world. Those guys are the definition of real-time. You can get daily and weekly statements, along with the typical monthly statements. Buying power, margin, etc, is all updated in real-time and viewable in their TWS software. Trading fees are definitely lower than Questrade unless you're routinely trading 800-1000+ shares. Most of my trades cost $1. Options have a lower limit before Questrade makes more sense. And nothing beats IB for forex. Ultimately it really depends on what you will be doing. Note that IB charges a minimum monthly fee of $10 ($3 if you're young and foolish). If you don't hit that with commissions, the balance is taken from your account. Also, all other fees are passed on to you (e.g. data, order cancellation). IB also doesn't have any registered accounts such as TFSA or RRSP, and doesn't plan to. If you'll be doing a bunch of hefty trading, IB offers a trading platform free of charge, but charges for everything else. Questrade instead has a monthly fee for its QuestraderPRO and QuestraderELITE services, but that includes data and flat rate commissions. If you're just looking for a place to invest cheaply without extra fees and plan on making a few trades a year, Questrade might be the right choice.",
"title": ""
},
{
"docid": "428284",
"text": "Many economists think that in a free market there would be more insider trading as they're able to more efficiently transmit pricing signals to the rest of the market. Can you come up with an argument how insider trading makes markets less free? What exactly is your definition of a free market?",
"title": ""
},
{
"docid": "395506",
"text": "No, at least not noticeably so. The majority of what HFT does is to take advantage of the fact that there is a spread between buy and sell orders on the exchange, and to instantly fill both orders, gaining relatively risk-free profit from some inherent inefficiencies in how the market prices stocks. The end result is that intraday trading of the non-HFT nature, as well as speculative short-term trading will be less profitable, since HFT will cause the buy/sell spread to be closer than it would otherwise be. Buying and holding will be (largely) unaffected since the spread that HFT takes advantage of is miniscule compared to the gains a stock will experience over time. For example, when you go to buy shares intending to hold them for a long time, the HFT might cost you say, 1 to 2 cents per share. When you go to sell the share, HFT might cost you the same again. But, if you held it for a long time, the share might have doubled or tripled in value over the time you held it, so the overall effect of that 2-4 cents per share lost from HFT is negligible. However, since the HFT is doing this millions of times per day, that 1 cent (or more commonly a fraction of a cent) adds up to HFTs making millions. Individually it doesn't affect anyone that much, but collectively it represents a huge loss of value, and whether this is acceptable or not is still a subject of much debate!",
"title": ""
},
{
"docid": "307518",
"text": "\"The stock market is not a zero-sum game. Some parts are (forex, some option trading), but plain old stock trading is not zero sum. That is to say, if you were to invest \"\"at random\"\", you would on average make money. That's because the market as a whole makes money - it goes up over time (6-10% annually, averaged over time). That's because you're not just gambling when you buy a stock; you're actually contributing money to a company (directly or indirectly), which it uses to fund activities that (on average) make money. When you buy Caterpillar stock, you're indirectly funding Caterpillar building tractors, which they then sell for a profit, and thus your stock appreciates in value. While not every company makes a profit, and thus not every stock appreciates in true value, the average one does. To some extent, buying index funds is pretty close to \"\"investing at random\"\". It has a far lower risk quotient, of course, since you're not buying a few stocks at random but instead are buying all stocks in an index; but buying stocks from the S&P 500 at random would on average give the same return as VOO (with way more volatility). So for one, you definitely could do worse than 50/50; if you simply sold the market short (sold random stocks short), you would lose money over time on average, above and beyond the transaction cost, since the market will go up over time on average. Secondly, there is the consideration of limited and unlimited gains or losses. Some trades, specifically some option trades, have limited potential gains, and unlimited potential losses. Take for example, a simple call option. If you sell a naked call option - meaning you sell a call option but don't own the stock - for $100, at a strike price of $20, for 100 shares, you make money as long as the price of that stock is under $21. You have a potential to make $100, because that's what you sold it for; if the price is under $20, it's not exercised, and you just get that $100, free. But, on the other hand, if the stock goes up, you could potentially be out any amount of money. If the stock trades at $24, you're out $400-100 = $300, right? (Plus transaction costs.) But what if it trades at $60? Or $100? Or $10000? You're still out 100 * that amount, so in the latter case, $1 million. It's not likely to trade at that point, but it could. If you were to trade \"\"at random\"\", you'd probably run into one of those types of situations. That's because there are lots of potential trades out there that nobody expects anyone to take - but that doesn't mean that people wouldn't be happy to take your money if you offered it to them. That's the reason your 16.66 vs 83.33 argument is faulty: you're absolutely right that if there were a consistently losing line, that the consistently winning line would exist, but that requires someone that is willing to take the losing line. Trades require two actors, one on each side; if you're willing to be the patsy, there's always someone happy to take advantage of you, but you might not get a patsy.\"",
"title": ""
},
{
"docid": "392852",
"text": "\"A TFSA is a tax free savings account. It is a type of account where you can buy various investments like stocks, bonds, or funds (mutual, exchange traded, and money market). There are some other options but it's best to see what your bank or broker will allow. You probably specified the type of investment when you opened the account. You can look at your statements or maybe online to see what you're invested in. My guess is some kind of HISA (high interest savings account). This is kind of the default option for banks. The government created these accounts for a variety of reasons. The main stated reason was to encourage people to save. Obviously they also do things to get votes. There was an outcry after the change to a type of investment called \"\"investment trusts\"\". This could be seen as a consolation prize. These can be valuable to seniors for many reasons and they tend to vote more often. There was also an election promise to eliminate capital gains taxes in some fashion. It's not profitable for the government, in fact it supposedly cost the federal government $410 million in 2013. Banks make money by investing your deposit or by charging fees. You can see what every tax break 'costs' the government in lost revenue here http://www.fin.gc.ca/taxexp-depfisc/2013/taxexp1301-eng.asp#toc7\"",
"title": ""
},
{
"docid": "245581",
"text": "If you need a performance bond - Performance Guarantee, Bronze Wing Trading is the right solution for you. We offer a complete solution to your bonds requirement at reasonable cost to guarantee your counter party for your performance of Trade Deal or Project. For a free quote, follow this link.",
"title": ""
},
{
"docid": "60728",
"text": "As you mentioned in the title, what you're asking about comes down to volatility. DCA when purchasing stock is one way of dealing with volatility, but it's only profitable if the financial instrument can be sold higher than your sunk costs. Issues to be concerned with: Let's suppose you're buying a stock listed on the NYSE called FOO (this is a completely fake example). Over the last six days, the average value of this stock was exactly $1.00Note 1. Over six trading days you put $100 per day into this stockNote 2: At market close on January 11th, you have 616 shares of FOO. You paid $596.29 for it, so your average cost (before fees) is: $596.29 / 616 = $0.97 per share Let's look at this including your trading fees: ($596.29 + $30) / 616 = $1.01 per share. When the market opens on January 12th, the quote on FOO could be anything. Patents, customer wins, wars, politics, lawsuits, press coverage, etc... could cause the value of FOO to fluctuate. So, let's just roll with the assumption that past performance is consistent: Selling FOO at $0.80 nets: (616 * $0.80 - $5) - ($596.29 + $30) = $123.49 Loss Selling FOO at $1.20 nets: (616 * $1.20 - $5) - ($596.29 + $30) = $107.90 Profit Every day that you keep trading FOO, those numbers get bigger (assuming FOO is a constant value). Also remember, even if FOO never changes its average value and volatility, your recoverable profits shrink with each transaction because you pay $5 in fees for every one. Speaking from experience, it is very easy to paper trade. It is a lot harder when you're looking at the ticker all day when FOO has been $0.80 - $0.90 for the past four days (and you're $300 under water on a $1000 portfolio). Now your mind starts playing nasty games with you. If you decide to try this, let me give you some free advice: Unless you have some research (such as support / resistance information) or data on why FOO is a good buy at this price, let's be honest: you're gambling with DCA, not trading. END NOTES:",
"title": ""
},
{
"docid": "489633",
"text": "\"It is very helpful to understand that Free File is not actually \"\"by\"\" the US Internal Revenue Service (IRS). The IRS does indeed offer access to the program through their website, but Free File is actually a public-private partnership program operated and maintained by the Free File Alliance. Who is the Free File Alliance? Well, according to their members list: 1040NOW Corp., Drake Enterprises, ezTaxReturn.com, FileYourTaxes, Free Tax Returns, H&R Block, Intuit, Jackson Hewitt, Liberty Tax, OnLine Taxes, TaxACT, TaxHawk, and TaxSlayer. Why the income restriction? Well, that's part of the deal the IRS struck - the program is \"\"dedicated to helping 70 percent of American taxpayers prepare and e-file their federal tax returns\"\". Technically the member companies are offering their own software to handle tax preparation, and the rule is that 70% of American's must 'qualify' for at least one product, so this adjusted gross income limit changes periodically so that 70% of the population can use it. Why restrict it at all? This was part of the give and take involved in negotiation with the businesses involved. If the program was \"\"everyone files for free\"\", then it is presumed that many reputable businesses that make the program valuable would choose not to continue to participate. In other words, they want to be able to not give away their services for free to customers who are - at least by income definition - more than capable of paying them. The IRS has said it does not want to be in the tax prep software business, so they are not offering their own free software to do the job that private companies would otherwise charge for. However, there are other restrictions to being in the program - like the fact that no business in the program can offer \"\"refund anticipation loans\"\", offer commercial services more than a certain amount of times (so they can't hound you to upgrade), and so on. Some businesses were making a killing off these, though they are pretty much solely developed to be predatory on people with the lowest incomes (and education levels, and IQ, and with cognitive disabilities, and basically anyone they could sucker into paying what were effectively absurd rates for short term loans along with inflated filing/preparation fees). Finally, Free File was partly developed as an initiative to increase the amount of digitally filed taxes and reduce the paper-based burdens of accepting and processing turns. In other words: to cut government costs, not to be a government welfare program. Even if it were, one can generally obtain commercial software for $30-$100, so the benefit to those above gross income levels is pretty minor; yearly costs to file taxes with such software for those payers would be less than 0.001% of their yearly expenses. Compared to the benefits obtainable by households living below the poverty line, fighting to cover an extra 5-30% of the population at the potential expense of having the whole program be a failure probably seemed like a more than worthwhile trade-off.\"",
"title": ""
},
{
"docid": "501885",
"text": "Free trade agreements are not about trade. Thats just their pretext. They use free trade agreements to get all sorts of things that legislators would never vote for. Now I hear the FTAs are putting the US taxpayer into a state of potential liability for a lot of financial hijinks in other countries, and - if they put exporting energy into [TTIP](http://www.ttip2014.eu), also making us liable if we decide to stop [the flow of energy, natural gas, overseas](http://action.sierraclub.org/site/DocServer/Analysis_of_EU_Energy_Proposal_TTIP.pdf) for many wholly legitimate reasons - we would be asked to pay huge amounts if we stopped it, say, because it was killing jobs here having energy cost twice or three times as much. thats not a good reason, just like not being able to affording healthcare for your country under the insurance system is [not a good enough reason](http://www.italaw.com/sites/default/files/case-documents/italaw3206.pdf) to switch to single payer without running afoul of an FTA once its been signed.",
"title": ""
},
{
"docid": "413856",
"text": "In terms of building the initial investment using some kind of mutual fund, I'd suggest you see my answer to this similar question https://money.stackexchange.com/questions/9943/cheapest-or-free-online-broker-for-beginner For buying individual stocks later, you could look at sharebuilder, or a low cost broker, however most of them charge between $5-$7 per trade, and if you are doing small dollar value trades then that can really really eat into things if you try to trade a lot.",
"title": ""
}
] |
920
|
“Occupation” field on IRS Form 1040
|
[
{
"docid": "166245",
"text": "\"It doesn't generally matter, and I'm not sure if it is in fact in use by the IRS other than for general statistics (like \"\"this year 20% of MFJ returns were with one spouse being a 'homemaker'\"\"). They may be able to try and match the occupation and the general levels and types of income, but for self-employed there's a more precise and reliable field on Schedule C and for employees they don't really need to do this since everything is reported on W2 anyway. So I don't think they even bother or give a lot of value to such a metric. So yes, I'm joining the non-authoritative \"\"doesn't matter\"\" crowd.\"",
"title": ""
}
] |
[
{
"docid": "174025",
"text": "You are right that even if you do not receive a 1099-MISC, you still need to report all income to the IRS. Report the $40 on Schedule C or Schedule C-EZ. Since your net profit was less than $400, you do not need to file Schedule SE. From the IRS web site: Self-Employment Income It is a common misconception that if a taxpayer does not receive a Form 1099-MISC or if the income is under $600 per payer, the income is not taxable. There is no minimum amount that a taxpayer may exclude from gross income. All income earned through the taxpayer’s business, as an independent contractor or from informal side jobs is self-employment income, which is fully taxable and must be reported on Form 1040. Use Form 1040, Schedule C, Profit or Loss from Business, or Form 1040, Schedule C-EZ, Net Profit from Business (Sole Proprietorship) to report income and expenses. Taxpayers will also need to prepare Form 1040 Schedule SE for self-employment taxes if the net profit exceeds $400 for a year. Do not report this income on Form 1040 Line 21 as Other Income. Independent contractors must report all income as taxable, even if it is less than $600. Even if the client does not issue a Form 1099-MISC, the income, whatever the amount, is still reportable by the taxpayer.",
"title": ""
},
{
"docid": "254151",
"text": "\"If you receive a 1099-MISC from YouTube, that tells you what they stated to the IRS and leads into most tax preparation software guided interviews or wizards as a topic for you to enter. Whether or not you have a 1099-MISC, this discussion from the IRS is pertinent to your question. You could probably elect to report the income as a royalty on your copyrighted work of art on Schedule E, but see this note: \"\"In most cases you report royalties in Part I of Schedule E (Form 1040). However, if you ... are in business as a self-employed writer, inventor, artist, etc., report your income and expenses on Schedule C or Schedule C-EZ (Form 1040).\"\" Whether reporting on Schedule E or C is more correct or better for your specific circumstances is beyond the advice you should take from strangers on the internet based on a general question - however, know that there are potentially several paths for you. Note that this is revenue from a business, so if you paid for equipment or services that are 100% dedicated to your YouTubing (PC, webcam, upgraded broadband, video editing software, vehicle miles to a shoot, props, etc.) then these are a combination of depreciable capital investments and expenses you can report against the income, reducing the taxes you may owe. If the equipment/services are used for business and personal use, there are further guidelines from the IRS as to estimating the split. These apply whether you report on Sch. E, Sch. C, or Sch C-EZ. Quote: \"\"Self-Employment Income It is a common misconception that if a taxpayer does not receive a Form 1099-MISC or if the income is under $600 per payer, the income is not taxable. There is no minimum amount that a taxpayer may exclude from gross income. All income earned through the taxpayer’s business, as an independent contractor or from informal side jobs is self-employment income, which is fully taxable and must be reported on Form 1040. Use Form 1040, Schedule C, Profit or Loss from Business, or Form 1040, Schedule C-EZ, Net Profit from Business (Sole Proprietorship) to report income and expenses. Taxpayers will also need to prepare Form 1040 Schedule SE for self-employment taxes if the net profit exceeds $400 for a year. Do not report this income on Form 1040 Line 21 as Other Income. Independent contractors must report all income as taxable, even if it is less than $600. Even if the client does not issue a Form 1099-MISC, the income, whatever the amount, is still reportable by the taxpayer. Fees received for babysitting, housecleaning and lawn cutting are all examples of taxable income, even if each client paid less than $600 for the year. Someone who repairs computers in his or her spare time needs to report all monies earned as self-employment income even if no one person paid more than $600 for repairs.\"\"\"",
"title": ""
},
{
"docid": "593938",
"text": "\"This may be relevant: it suggests that IRS is lenient with the attachment of the form with 1040. To paraphrase: \"\"The ruling involved a taxpayer who timely filed the election with the IRS within 30 days of the property transfer but who did not attach a copy of the election to his or her Form 1040 for the year of the transfer. Fortunately for the taxpayer in question, the ruling indicated that the submission of the election to the IRS within 30 days of the property transfer fulfilled the requirements for a valid election, and the failure to attach the copy to the tax return did not affect the validity of the election. The IRS requested that the taxpayer forward a copy of the election to the IRS to be associated with the processing of the tax return. - See more at: http://www.bnncpa.com/services/employee_benefit_plans/blog/irs_rules_that_failure_to_attach_83b_election_to_form_1040_did_not_invalida#sthash.0c3h2nJY.dpuf\"\" If someone wants to grok the IRS ruling: http://www.irs.gov/pub/irs-wd/1405008.pdf And this is the article where I saw the above referenced. www.bnncpa.com/services/employee_benefit_plans/blog/irs_rules_that_failure_to_attach_83b_election_to_form_1040_did_not_invalida\"",
"title": ""
},
{
"docid": "57707",
"text": "\"Depending on what you need to explain, you can submit your electronic return without the supplemental information and subsequently mail a Form 8453 with the additional information. This is helpful for form 8489, for example, where you need to list every transaction reported by your stock broker on a 1099-B. See https://www.irs.gov/pub/irs-pdf/f8453.pdf for more details on this form. If the information you need to submit an attachment for doesn't follow one of the options on that form, you will likely need to file a paper return or use a paid tax preparation service/application. Limitations of FreeFile are explained here, along with a list of forms that are available: https://www.irs.gov/uac/List-of-Available-Free-File-Fillable-Forms The \"\"Attaching Statements\"\" and \"\"Write-in information\"\" sections seem like they might apply to your situation. Attaching Statements - If you need to add statements and you can't use Form 8453, U.S. Individual Income Tax Transmittal for an IRS e-file Return, to mail that information, you will not be able to use this program to efile your return Identity Protection PIN's (IP PIN) - This program only supports the entry of a Primary taxpayer's IP PIN. If the spouse or dependents have an IP PIN, you cannot use this program to efile the return. Writing In Information - Your ability to \"\"write in\"\" additional information to explain an entry is generally limited to the 1040 forms and some of the more frequently submitted forms. If you need to write in additional information on a form, other than the 1040 series, you may not be able to use this program to efile your tax return. E-filing Forms - To efile forms, (except Form 4868) they must be attached to a 1040 series form (1040, 1040A or 1040EZ). Form Limitations - There may be Known Limitations of forms you plan to complete. Please review them. A form limitation may keep you from completing or e-filing your return.\"",
"title": ""
},
{
"docid": "211869",
"text": "is it possible to file that single form aside from the rest of my return? Turbotax will generate all the forms necessary to file your return. I recommend you access these forms and file them manually. According to the IRS in order to report capital gains and losses you need to fill out Form 8949 and summarize them on Form 1040 D. Add these two forms to the stack that turbotax generates. Add the total capital gains to line 13 of the Form 1040 which turbotax generated, and adjust the totals on the form accordingly.",
"title": ""
},
{
"docid": "219156",
"text": "\"If you want an \"\"account statement\"\" from the IRS listing the taxes due and paid and confirming a zero balance remaining, you want what they call a Tax Account Transcript. It sounds like you tried to submit this online, but yes, it would require the actual taxpayer to submit it. The other option would be to fill out Form 4506-T requesting the Form 1040 Tax Account Transcript, have the taxpayer sign it, and mail it in. Presumably whatever method you used to have her sign the Form 1040 you prepared for her you could also use to have her sign the 4506-T. Another option could be to try to request the transcript over the phone. I don't know what authentication they require, or if you would need to have been listed on the 1040 as an authorized Third Party Designee. According to the IRS Transcript FAQ Page: Q19. What if I’m unable to use Get Transcript by Mail? If you are unable to use Get Transcript by Mail, you may try our automated phone transcript service at 800-908-9946 and also receive your transcript by mail. Please allow 5 to 10 calendar days for delivery. But unless there's a reason to think that the tax account wasn't credited properly or the IRS is sending another bill or the like, I don't think there's a lot of point in doing so. In general, the fact that the check cleared the bank should be sufficient documentation that the amount was paid.\"",
"title": ""
},
{
"docid": "436960",
"text": "They are four quarterly estimated tax payments. The IRS requires that you pay your taxes throughout the year (withholding in a W-2 job). You'll need to estimate how much taxes you think you might be owing and then pay roughly 1/4 at each of the 4 deadlines. From the IRS: How To Figure Estimated Tax To figure your estimated tax, you must figure your expected AGI, taxable income, taxes, deductions, and credits for the year. When figuring your 2011 estimated tax, it may be helpful to use your income, deductions, and credits for 2010 as a starting point. Use your 2010 federal tax return as a guide. You can use Form 1040-ES to figure your estimated tax. Nonresident aliens use Form 1040-ES (NR) to figure estimated tax. You must make adjustments both for changes in your own situation and for recent changes in the tax law. For 2011, there are several changes in the law. Some of these changes are discussed under What's New for 2011 beginning on page 2. For information about these and other changes in the law, visit the IRS website at IRS.gov. The instructions for Form 1040-ES include a worksheet to help you figure your estimated tax. Keep the worksheet for your records. You may find some value from hiring a CPA to help you setup your estimated tax payments and amounts.",
"title": ""
},
{
"docid": "69333",
"text": "\"There could be a few reasons for this, my first guess is that you didn't report the distribution on your return (indicated on line 15 of your 1040, pictured below), the IRS got a copy of the 1099-R, and assumes it's all taxable (or maybe the 1099-R indicates the full amount is taxable). If a 1099-R doesn't have an amount populated for 'taxable amount' it doesn't mean the distribution isn't taxable, and without any indication that it's not taxable the IRS assumes it is. It's not taxable if it's a withdrawal of your contribution. Here's a snippet from How to Calculate the Taxable Amount of an IRA Withdrawal: Withdrawals from a Roth IRA Since Roth IRA contributions are made on an after-tax basis, qualified withdrawals are completely tax-free. A \"\"qualified\"\" Roth withdrawal includes the following: If your 1099-R indicates a taxable amount, then you might need to contact the issuer to understand why. If it does not indicate a taxable amount and you failed to record the distribution on your return, you just need to file an amended return that shows the distribution on line 15a and shows no taxable amount on 15b along with a completed Form 8606. You may not need additional documentation to support of your claim that it's not taxable, but if you do it would be any statement showing that your contributions over the years exceed your withdrawal. What a 1040 with a non-taxable IRA withdrawal would show: Note: There'd also be a completed Form 8606, the 1040 lines above just show if it was entered in. The easiest path forward is probably to file an amended return using turbotax since you filed with them originally. I haven't dealt with an IRS letter in a few years, I can't recall if you need to contact them or simply file the amended return, but they're pretty good about including instructions so the letter probably indicates what you need to do. Don't delay in taking action, as the IRS can and will garnish wages if they are owed (or think they are owed) money. Update: OP contacted IRS and they didn't even want an amended return, just the completed Form 8606, so it's worth calling the IRS first with these letters.\"",
"title": ""
},
{
"docid": "223624",
"text": "Yes, you need to include income from your freelance work on your tax return. In the eyes of the IRS, this is self-employment income from your sole-proprietorship business. The reason you don't see it mentioned in the 1040EZ instructions is that you can't use the 1040EZ form if you have self-employment income. You'll need to use the full 1040 form. Your business income and expenses will be reported on a Schedule C or Schedule C-EZ, and the result will end up on Line 12 of the 1040. Take a look at the requirements at the top of the C-EZ form; you probably meet them and can use it instead of the more complicated C form. If you have any deductible business expenses related to your freelance business, this would be done on Schedule C or C-EZ. If your freelance income was more than $400, you'll also need to pay self-employment tax. To do this, you file Schedule SE, and the tax from that schedule lands on form 1040 Line 57.",
"title": ""
},
{
"docid": "450808",
"text": "\"One way to do these sorts of calculations is to use the spreadsheet version of IRS form 1040 available here. This is provided by a private individual and is not an official IRS tool, but in practice it is usually accurate enough for these purposes. You may have to spend some time figuring out where to enter the info. However, if you enter your self-employment income on Schedule C, this spreadsheet will calculate the self-employment tax as well as the income tax. An advantage is that it is the full 1040, so you can also select the standard deduction and the number of exemptions you are entitled to, enter ordinary W-2 income, even capital gains, etc. Of course you can also make use of other tax software to do this, but in my experience the \"\"Excel 1040\"\" is more convenient, as most websites and tax-prep software tend to be structured in a linear fashion and are more cumbersome to update in an ad-hoc way for purposes like tax estimation. You can do whatever works for you, but I would recommend taking a look at the Excel 1040. It is a surprisingly useful tool.\"",
"title": ""
},
{
"docid": "216404",
"text": "Generally stock trades will require an additional Capital Gains and Losses form included with a 1040, known as Schedule D (summary) and Schedule D-1 (itemized). That year I believe the maximum declarable Capital loss was $3000--the rest could carry over to future years. The purchase date/year only matters insofar as to rank the lot as short term or long term(a position held 365 days or longer), short term typically but depends on actual asset taxed then at 25%, long term 15%. The year a position was closed(eg. sold) tells you which year's filing it belongs in. The tiny $16.08 interest earned probably goes into Schedule B, typically a short form. The IRS actually has a hotline 800-829-1040 (Individuals) for quick questions such as advising which previous-year filing forms they'd expect from you. Be sure to explain the custodial situation and that it all recently came to your awareness etc. Disclaimer: I am no specialist. You'd need to verify everything I wrote; it was just from personal experience with the IRS and taxes.",
"title": ""
},
{
"docid": "128861",
"text": "Such activity is normally referred to as bartering income. From the IRS site - You must include in gross income in the year of receipt the fair market value of goods or services received from bartering. Generally, you report this income on Form 1040, Schedule C (PDF), Profit or Loss from Business (Sole Proprietorship), or Form 1040, Schedule C-EZ (PDF), Net Profit from Business (Sole Proprietorship). If you failed to report this income, correct your return by filing a Form 1040X (PDF), Amended U.S. Individual Income Tax Return. Refer to Topic 308 and Amended Returns for information on filing an amended return.",
"title": ""
},
{
"docid": "466718",
"text": "\"From the poster's description of this activity, it doesn't look like he is engaged in a business, so Schedule C would not be appropriate. The first paragraph of the IRS Instructions for Schedule C is as follows: Use Schedule C (Form 1040) to report income or loss from a business you operated or a profession you practiced as a sole proprietor. An activity qualifies as a business if your primary purpose for engaging in the activity is for income or profit and you are involved in the activity with continuity and regularity. For example, a sporadic activity or a hobby does not qualify as a business. To report income from a nonbusiness activity, see the instructions for Form 1040, line 21, or Form 1040NR, line 21. What the poster is doing is acting as a nominee or agent for his members. For instance, if I give you $3.00 and ask you to go into Starbucks and buy me a pumpkin-spice latte, you do not have income or receipts of $3.00, and you are not engaged in a business. The amounts that the poster's members are forwarding him are like this. Money that the poster receives for his trouble should be reported as nonbusiness income on Line 21 of Form 1040, in accordance with the instructions quoted above and the instructions for Form 1040. Finally, it should be noted that the poster cannot take deductions or losses relating to this activity. So he can't deduct any expenses of organizing the group buy on his tax return. Of course, this would not be the case if the group buy really is the poster's business and not just a \"\"hobby.\"\" Of course, it goes without saying that the poster should document all of this activity with receipts, contemporaneous emails (and if available, contracts) - as well as anything else that could possibly be relevant to proving the nature of this activity in the event of an audit.\"",
"title": ""
},
{
"docid": "284085",
"text": "You need to file IRS Form 1040-NR. The IRS's website provides instructions.",
"title": ""
},
{
"docid": "55407",
"text": "According to pages 6 & 7 of the instructions for form 1040 in 2009 AMT was only temporarily patched for the year. Congress can't politically afford to drastically cut AMT exemptions by 30 to 40%, and may even retroactively change it, if it isn't passed by the end of the year (despite the constitution forbidding ex post facto laws) : What’s New for 2009 ... Alternative minimum tax (AMT) exemption amount increased. The AMT exemption amount has increased to $46,700 ($70,950 if married filing jointly or a qualifying widow(er); $35,475 if married filing separately)... What’s New for 2010 ... Alternative minimum tax (AMT) exemption amount. The AMT exemption amount is scheduled to decrease to $33,750 ($45,000 if married filing jointly or a qualifying widow(er); $22,500 if married filing separately). So, if you are married, and several regular tax deductions push your income below the AMT exemption amount of $45,000, it's quite possible you would be required to pay AMT, even if you didn't last year. There is a work sheet for AMT in the instructions for line 43, but the IRS also provides an AMT calculator. According to page 146 (E-8) of the instructions for form 1040 AMT is paid as: the smallest amount you are allowed to report as your taxable income (Form 1040, line 43). It is also the smallest amount you are allowed to report as your alternative minimum taxable income (AMTI) on Form 6251, line 29. If the [AMT calculation] is larger than your taxable income would otherwise be, enter the amount from column (c) on Form 1040, line 43 [or ...] Form 6251, line 29. As always, congress finds ways to further complicate things by making a few credits and losses deductible against the absolute minimum you're expected to pay taxes on, making the AMT a misnomer.",
"title": ""
},
{
"docid": "29300",
"text": "It is true that with a job that pays you via payroll check that will result in a W-2 because you are an employee, the threshold that you are worried about before you have to file is in the thousands. Unless of course you make a lot of money from bank interest or you have income tax withheld and you want it refunded to you. Table 2 and table 3 in IRS pub 501, does a great job of telling you when you must. For you table 3 is most likely to apply because you weren't an employee and you will not be getting a W-2. If any of the five conditions listed below applied to you for 2016, you must file a return. You owe any special taxes, including any of the following. a. Alternative minimum tax. (See Form 6251.) b. Additional tax on a qualified plan, including an individual retirement arrangement (IRA), or other taxfavored account. (See Pub. 590A, Contributions to Individual Retirement Arrangements (IRAs); Pub. 590B, Distributions from Individual Retirement Arrangements (IRAs); and Pub. 969, Health Savings Accounts and Other TaxFavored Health Plans.) But if you are filing a return only because you owe this tax, you can file Form 5329 by itself. c. Social security or Medicare tax on tips you didn't report to your employer (see Pub. 531, Reporting Tip Income) or on wages you received from an employer who didn't withhold these taxes (see Form 8919). d. Writein taxes, including uncollected social security, Medicare, or railroad retirement tax on tips you reported to your employer or on groupterm life insurance and additional taxes on health savings accounts. (See Pub. 531, Pub. 969, and the Form 1040 instructions for line 62.) e. Household employment taxes. But if you are filing a return only because you owe these taxes, you can file Schedule H (Form 1040) by itself. f. Recapture taxes. (See the Form 1040 instructions for lines 44, 60b, and 62.) You (or your spouse if filing jointly) received Archer MSA, Medicare Advantage MSA, or health savings account distributions. You had net earnings from selfemployment of at least $400. (See Schedule SE (Form 1040) and its instructions.) You had wages of $108.28 or more from a church or qualified churchcontrolled organization that is exempt from employer social security and Medicare taxes. (See Schedule SE (Form 1040) and its instructions.) Advance payments of the premium tax credit were made for you, your spouse, or a dependent who enrolled in coverage through the Health Insurance Marketplace. You should have received Form(s) 1095A showing the amount of the advance payments, if any. It appears that item 3: You had net earnings from selfemployment of at least $400. (See Schedule SE (Form 1040) and its instructions.) would most likely apply. It obviously is not too late to file for 2016, because taxes aren't due for another month. As to previous years that would depend if you made money those years, and how much.",
"title": ""
},
{
"docid": "201658",
"text": "No, you don't have to have the money deducted from your paycheck. The IRS doesn't get a copy of your paycheck anyway. When you file your annual tax return (form 1040), there's a line there to write down the amount you contributed to the IRA. In fact, you can contribute to the IRA after the year ended, until the Tax Day of the next year, so that you can make sure your contribution will actually be deductible (not always they are). The IRA custodian (the brokerage firm/bank where you opened the IRA account) will provide you with a deposit confirmation and form 5498. A copy of form 5948 is also sent to the IRS.",
"title": ""
},
{
"docid": "411063",
"text": "Through your question and then clarification through the comments, it looks like you have a U.S. LLC with at least two members. If you did not elect some other tax treatment, your LLC will be treated as a partnership by the IRS. The partnership should file a tax return on Form 1065. Then each partner will get a Schedule K-1 from the partnership, which the partner should use to include their respective shares of the partnership income and expenses on their personal Forms 1040. You can also elect to be taxed as an S-Corp or a C-Corp instead of a partnership, but that requires you to file a form explicitly making such election. If you go S-Corp, then you will file a different form for the company, but the procedure is roughly the same - Income gets passed through to the owners via a Schedule K-1. If you go C-Corp, then the owners will pay no tax on their own Form 1040, but the C-Corp itself will pay income tax. As far as whether you should try to spend the money as business expense to avoid paying extra tax - That's highly dependent on your specific situation. I'd think you'd want to get tailored advice for that.",
"title": ""
},
{
"docid": "268069",
"text": "Generally, prize money is miscellaneous income, reported on line 21 of your 1040 and not subject to self employment tax. See IRS publication 525 for more details; under 'Prizes and Awards', they give an example of winning a photography contest. Now, there are a couple of exceptions. If your main occupation is participating in contests such as this - or you do it sufficiently that it could be considered such - then it may be considered something you should pay self employment taxes on. If it's your first one - you're fine. Also, it would have to be something that doesn't look like work for me to be confident it's self employment income. I'm not sure that winning the Netflix prize for improving on their algorithm by 10% wouldn't run the risk of being considered sort of employment. I'm not a tax advisor, but in that case I would hire one to be sure. I could imagine companies abusing 'prizes' otherwise to get out of paying employment taxes...",
"title": ""
},
{
"docid": "442146",
"text": "Yes, you can send in a 2012 1040-ES form with a check to cover your tax liability. However, you will likely have to pay penalties for not paying tax in timely fashion as well as interest on the late payment. You can have the IRS figure the penalty and bill you for it, or you can complete Form 2210 (on which these matters are figured out) yourself and file it with your Form 1040. The long version of Form 2210 often results in the smallest extra amount due but is considerably more time-consuming to complete correctly. Alternatively, if you or your wife have one or more paychecks coming before the end of 2012, it might be possible to file a new W-4 form with the HR Department with a request to withhold additional amounts as Federal income tax. I say might because if the last paycheck of the year will be issued in just a few days' time, it might already have been sent for processing, and HR might tell you it is too late. But, depending on the take-home pay, it might be possible to have the entire $2000 withheld as additional income tax instead of sending in a 1040-ES. The advantage of doing it through withholding is that you are allowed to treat the entire withholding for 2012 as satisfying the timely filing requirements. So, no penalty for late payment even though you had a much bigger chunk withheld in December, and no interest due either. If you do use this approach, remember that Form W-4 applies until it is replaced with another, and so HR will continue to withhold the extra amount on your January paychecks as well. So, file a new W-4 in January to get back to normal withholding. (Fix the extra exemption too so the problem does not recur in 2013).",
"title": ""
},
{
"docid": "257443",
"text": "I assume the OP is the US and that he is, like most people, a cash-basis tax payer and not an accrual basis tax payer. Suppose the value of the rental of the unit the OP is occupying was reported as income on the OP's 2010 and 2011 W-2 forms but the corresponding income tax was not withheld. If the OP correctly transcribed these income numbers onto his tax returns, correctly computed the tax on the income reported on his 2010 and 2011 1040 forms, and paid the amount due in timely fashion, then there is no tax or penalty due for 2010 and 2011. Nor is the company entitled to withhold tax on this income for 2010 and 2011 at this time; the tax on that income has already been paid by the OP directly to the IRS and the company has nothing to do with the matter anymore. Suppose the value of the rental of the unit the OP is occupying was NOT reported as income on the OP's 2010 and 2011 W-2 forms. If the OP correctly transcribed these income numbers onto his tax returns, correctly computed the tax on the income reported on his 2010 and 2011 1040 forms, and paid the amount due in timely fashion, then there is no tax or penalty due for 2010 and 2011. Should the OP have declared the value of the rental of the unit as additional income from his employer that was not reported on the W-2 form, and paid taxes on that money? Possibly, but it would be reasonable to argue that the OP did nothing wrong other than not checking his W-2 form carefully: he simply assumed the income numbers included the value of the rental and copied whatever the company-issued W-2 form said onto his 1040 form. At least as of now, there is no reason for the IRS to question his 2010 and 2011 returns because the numbers reported to the IRS on Copy A of the W-2 forms match the numbers reported by the OP on his tax returns. My guess is that the company discovered that it had not actually declared the value of the rental payments on the OP's W-2 forms for 2010 and 2011 and now wants to include this amount as income on subsequent W-2 forms. Now, reporting a lump-sum benefit of $38K (but no actual cash) would have caused a huge amount of income tax to need to be withheld, and the OP's next couple of paychecks might well have had zero take-home pay as all the money was going towards this tax withholding. Instead, the company is saying that it will report the $38K as income in 78 equal installments (weekly paychecks over 18 months?) and withhold $150 as the tax due on each installment. If it does not already do so, it will likely also include the value of the current rent as a benefit and withhold tax on that too. So the OP's take-home pay will reduce by $150 (at least) and maybe more if the current rental payments also start appearing on the paychecks and tax is withheld from them too. I will not express an opinion on the legality of the company withholding an additional $150 as tax from the OP's paycheck, but will suggest that the solution proposed by the company (have the money appear as taxable benefits over a 78-week period, have tax withheld, and declare the income on your 2012, 2013 and 2014 returns) is far more beneficial to the OP than the company declaring to the IRS that it made a mistake on the 2010 and 2011 W-2's issued to the OP, and that the actual income paid was higher. Not only will the OP have to file amended returns for 2010 and 2011 but the company will need to amend its tax returns too. In summary, the OP needs to know that He will have to pay taxes on the value of the waived rental payments for 2010 and 2011. The company's mistake in not declaring this as income to the OP for 2010 and 2011 does not absolve him of the responsibility for paying the taxes What the company is proposing is a very reasonable solution to the problem of recovering from the mistake. The alternative, as @mhoran_psprep points out, is to amend your 2010 and 2011 federal and state tax returns to declare the value of the rental during those years as additional income, and pay taxes (and possibly penalties) on the additional amount due. This takes the company completely out of the picture, but does require a lot more work and a lot more cash now rather than in the future.",
"title": ""
},
{
"docid": "444246",
"text": "If you have a one-time event, you are allowed to make a single estimated payment for that quarter on Form 1040-ES. People seem to fear that if they make one such payment they will need to do it forevermore, and that is not true. The IRS instructions do kind of read that way, but that's because most people who make estimated payment do so because of some repeating circumstance like being self-employed. In addition, you may qualify for one or more waivers on a potential underpayment penalty when you file your Form 1040 even if you don't make an estimated payment, and you may reduce or eliminate any penalty by annualizing your income - which is to say breaking it down by quarter rather than the full year. Check on the instructions for Form 2210 for more detail, including Schedule AI for annualizing income. This is some work, but it might be worthwhile depending on your situation. https://www.irs.gov/instructions/i2210/ch02.html",
"title": ""
},
{
"docid": "574417",
"text": "\"When you do your taxes, you have two choices for your deductions. You can take the standard deduction, or you can choose to itemize your deductions. If you itemize your deductions, you use Form 1040 Schedule A. By looking at Schedule A, you can see the list of deductions that are itemized: On Schedule A itself, you only list a total for each of these broad categories. In some cases, this is sufficient detail. However, for certain deductions, finer detail may be required, and you may have to submit additional forms showing this detail. For example, on the medical expense line, you generally only list a total of medical expenses; details are only supplied to the IRS upon request. For noncash gifts to charity, you need to supply more details on Form 8283 if your gifts are worth more than $500. These requirements can be found in the instructions for Schedule A. As noted by @Accumulation in the comments, the above deductions that are a part of your itemized deductions are called \"\"below the line\"\" deductions (because they are subtracted after the adjusted gross income line) and are only able to be deducted if you choose to decline the standard deduction. There are other deductions that are available whether or not you itemize. These \"\"above the line\"\" deductions are found on Form 1040 Lines 23-35. If you look at these lines on the form, you'll see the different types of deductions that are called out here. Some of these deductions require additional details on other forms; for example, the HSA deduction requires details on Form 8889. If you have a business, your business expenses are not part of your itemized deductions at all, and do not appear on Schedule A anywhere. Instead, your business expenses get subtracted from your business's revenue, and the resulting profit (or loss) is what is reported on your Form 1040. Different types of businesses report these expenses differently. If you have a sole proprietorship, the details of your business's expenses are reported on Schedule C. On this schedule, Part II is devoted to deductible business expenses. Take a look at Schedule C, and you'll see that Lines 8-27 are different categories of expenses that get called out on this schedule.\"",
"title": ""
},
{
"docid": "206597",
"text": "The rebate amount is a non-qualified distribution: IRS Pub 969 describes how the HSA works: Reporting Distributions on Your Return How you report your distributions depends on whether or not you use the distribution for qualified medical expenses (defined earlier). If you use a distribution from your HSA for qualified medical expenses, you do not pay tax on the distribution but you have to report the distribution on Form 8889. However, the distribution of an excess contribution taken out after the due date, including extensions, of your return is subject to tax even if used for qualified medical expenses. Follow the instructions for the form and file it with your Form 1040 or Form 1040NR. If you do not use a distribution from your HSA for qualified medical expenses, you must pay tax on the distribution. Report the amount on Form 8889 and file it with your Form 1040 or Form 1040NR. If you have a taxable HSA distribution, include it in the total on Form 1040 or Form 1040NR, line 21, and enter “HSA” and the amount on the dotted line next to line 21. You may have to pay an additional 20% tax on your taxable distribution. I looked at several plans regarding how to handle mistaken distributions: example A What if I accidentally use my HSA Visa debit card for a non-qualified expense? To fix this problem, just bring that same amount into any local branch and tell us it was a Mistaken Distribution. We can then put the funds back into your HSA and correct the problem. example B You’re allowed to correct mistaken HSA withdrawals when there is clear and convincing evidence that amounts were distributed from an HSA because of a mistake of fact due to reasonable cause. You can correct the mistake by repaying the withdrawal no later than April 15 following the first year that you knew or should have known that the withdrawal was a mistake. When a correction is made, the mistaken withdrawal does not have to be included in gross income or be subject to the 6 percent additional tax, and the repayment does not count as an excess contribution. If an error is made by SelectAccount in its role as the administrator, SelectAccount will be responsible for taking appropriate corrective action. Check with your plan trustee on their procedure to fix the mistaken withdrawal.",
"title": ""
},
{
"docid": "496820",
"text": "When you invest (say $1000) in (say 100 shares) of a mutual fund at $10 per share, and the price of the shares changes, you do not have a capital gain or loss, and you do not have to declare anything to the IRS or make any entry on any line on Form 1040 or tell anyone else about it either. You can brag about it at parties if the share price has gone up, or weep bitter tears into your cocktail if the price has gone down, but the IRS not only does not care, but it will not let you deduct the paper loss or pay taxes on the paper gain. What you put down on Form 1040 Schedules B and D is precisely what the mutual fund will tell you on Form 1099-DIV (and Form 1099-B), no more, no less. If you did not report any of these amounts on your previous tax returns, you need to file amended tax returns, both Federal as well as State, A stock mutual fund invests in stocks and the fund manager may buy and sell some stocks during the course of the year. If he makes a profit, that money will be distributed to the share holders of the mutual fund. That money can be re-invested in more shares of the same mutual fund or taken as cash (and possibly invested in some other fund). This capital gain distribution is reported to you on Form 1099-DIV and you have to report sit on your tax return even if you re-invested in more share of the same mutual fund, and the amount of the distribution is taxable income to you. Similarly, if the stocks owned by the mutual fund pay dividends, those will be passed on to you as a dividend distribution and all the above still applies. You can choose to reinvest, etc, the amount will be reported to you on Form 1099-DIV, and you need to report it to the IRS and include it in your taxable income. If the mutual fund manager loses money in the buying and selling he will not tell you that he lost money but it will be visible as a reduction in the price of the shares. The loss will not be reported to you on Form 1099-DIV and you cannot do anything about it. Especially important, you cannot declare to the IRS that you have a loss and you cannot deduct the loss on your income tax returns that year. When you finally sell your shares in the mutual fund, you will have a gain or loss that you can pay taxes on or deduct. Say the mutual fund paid a dividend of $33 one year and you re-invested the money into the mutual fund, buying 3 shares at the then cost of $11 per share. You declare the $33 on your tax return that year and pay taxes on it. Two years later, you sell all 103 shares that you own for $10.50 per share. Your total investment was $1000 + $33 = $1033. You get $1081.50 from the fund, and you will owe taxes on $1081.50 - $1033 = $48.50. You have a profit of $50 on the 100 shares originally bought and a loss of $1.50 on the 3 shares bought for $11: the net result is a gain of $48.50. You do not pay taxes on $81.50 as the profit from your original $1000 investment; you pay taxes only on $48.50 (remember that you already paid taxes on the $33). The mutual fund will report on Form 1099-B that you sold 103 shares for $1081.50 and that you bought the 103 shares for an average price of $1033/103 = $10.029 per share. The difference is taxable income to you. If you sell the 103 shares for $9 per share (say), then you get $927 out of an investment of $1033 for a capital loss of $106. This will be reported to you on Form 1099-B and you will enter the amounts on Schedule D of Form 1040 as a capital loss. What you actually pay taxes on is the net capital gain, if any, after combining all your capital gains and losses for the year. If the net is a loss, you can deduct up to $3000 in a year, and carry the rest forward to later years to offset capital gains in later years. But, your unrealized capital gains or losses (those that occur because the mutual fund share price goes up and down like a yoyo while you grin or grit your teeth and hang on to your shares) are not reported or deducted or taxed anywhere. It is more complicated when you don't sell all the shares you own in the mutual fund or if you sell shares within one year of buying them, but let's stick to simple cases.",
"title": ""
},
{
"docid": "435405",
"text": "\"(Insert the usual disclaimer that I'm not any sort of tax professional; I'm just a random guy on the Internet who occasionally looks through IRS instructions for fun. Then again, what you're doing here is asking random people on the Internet for help, so here goes.) The gigantic book of \"\"How to File Your Income Taxes\"\" from the IRS is called Publication 17. That's generally where I start to figure out where to report what. The section on Royalties has this to say: Royalties from copyrights, patents, and oil, gas, and mineral properties are taxable as ordinary income. In most cases, you report royalties in Part I of Schedule E (Form 1040). However, if you hold an operating oil, gas, or mineral interest or are in business as a self-employed writer, inventor, artist, etc., report your income and expenses on Schedule C or Schedule C-EZ (Form 1040). It sounds like you are receiving royalties from a copyright, and not as a self-employed writer. That means that you would report the income on Schedule E, Part I. I've not used Schedule E before, but looking at the instructions for it, you enter this as \"\"Royalty Property\"\". For royalty property, enter code “6” on line 1b and leave lines 1a and 2 blank for that property. So, in Line 1b, part A, enter code 6. (It looks like you'll only use section A here as you only have one royalty property.) Then in column A, Line 4, enter the royalties you have received. The instructions confirm that this should be the amount that you received listed on the 1099-MISC. Report on line 4 royalties from oil, gas, or mineral properties (not including operating interests); copyrights; and patents. Use a separate column (A, B, or C) for each royalty property. If you received $10 or more in royalties during 2016, the payer should send you a Form 1099-MISC or similar statement by January 31, 2017, showing the amount you received. Report this amount on line 4. I don't think that there's any relevant Expenses deductions you could take on the subsequent lines (though like I said, I've not used this form before), but if you had some specific expenses involved in producing this income it might be worth looking into further. On Line 21 you'd subtract the 0 expenses (or subtract any expenses you do manage to list) and put the total. It looks like there are more totals to accumulate on lines 23 and 24, which presumably would be equally easy as you only have the one property. Put the total again on line 26, which says to enter it on the main Form 1040 on line 17 and it thus gets included in your income.\"",
"title": ""
},
{
"docid": "461527",
"text": "No, always give the most current address information to the IRS, not least because they will use this address to send you important communications, such as refund checks or notices of deficiency. Per the 1040 Instructions, you should put in your address, with no mention of past addresses. Moreover, if you will change addresses after filing, the IRS has provided Form 8822 to notify them of the new address. There is a similar Form 8822-B for business addresses. They will use your Social Security Number (SSN), Individual Taxpayer Identification Number (ITIN), or Employer Identification Number (EIN) to track who you are. There's no point to purposely giving an invalid address, and in fact it's technically illegal since you will sign and certify the return as true and accurate to the best of your knowledge.",
"title": ""
},
{
"docid": "14776",
"text": "\"Yes, it is, but first let me address this sentence: my current withholding on my W4 is already at 0 so I can't make it lower You definitely can make it lower. On W4, in addition to the allowances (that what you meant by \"\"already at 0\"\"), there's also a line called \"\"additional withholding\"\". There, you put the dollar amount that you want your payroll to withhold from your paycheck each pay period. So the easiest way to \"\"send\"\" a one time payment to the IRS, if you're a W2 employee, would be to adjust that line with the amount you want to send, and change it back to 0 next pay period. You can also send a check directly to the IRS - follow the instructions to form 1040-ES. That is exactly what that form is designed to be used for.\"",
"title": ""
},
{
"docid": "293687",
"text": "\"Yes, you can do that, but you have to have the stocks issued in your name (stocks that you're holding through your broker are issued in \"\"street name\"\" to your broker). If you have a physical stock certificate issued in your name - you just endorse it like you would endorse a check and transfer the ownership. If the stocks don't physically exist - you let the stock registrar know that the ownership has been transferred to someone else. As to the price - the company doesn't care much about the price of private sales, but the taxing agency will. In the US, for example, you report such a transaction as either a gift (IRS form 709), if the transaction was at a price significantly lower than the FMV (or significantly higher, on the other end), or a sale (IRS form 1040, schedule D) if the transaction was at FMV.\"",
"title": ""
},
{
"docid": "487728",
"text": "I strongly recommend that you talk to an accountant right away because you could save some money by making a tax payment by January 15, 2014. You will receive Forms 1099-MISC from the various entities with whom you are doing business as a contractor detailing how much money they paid you. A copy will go to the IRS also. You file a Schedule C with your Form 1040 in which you detail how much you received on the 1099-MISC forms as well as any other income that your contracting business received (e.g. amounts less than $600 for which a 1099-MISc does not need to be issued, or tips, say, if you are a taxi-driver running your own cab), and you can deduct various expenses that you incurred in generating this income, including tools, books, (or gasoline!) etc that you bought for doing the job. You will need to file a Schedule SE that will compute how much you owe in Social Security and Medicare taxes on the net income on Schedule C. You will pay at twice the rate that employees pay because you get to pay not only the employee's share but also the employer's share. At least, you will not have to pay income tax on the employer's share. Your net income on Schedule C will transfer onto Form 1040 where you will compute how much income tax you owe, and then add on the Social Security tax etc to compute a final amount of tax to be paid. You will have to pay a penalty for not making tax payments every quarter during 2013, plus interest on the tax paid late. Send the IRS a check for the total. If you talk to an accountant right away, he/she will likely be able to come up with a rough estimate of what you might owe, and sending in that amount by January 15 will save some money. The accountant can also help you set up for the 2014 tax year during which you could make quarterly payments of estimated tax for 2014 and avoid the penalties and interest referred to above.",
"title": ""
}
] |
500
|
Headaches are correlated with cognitive impairment.
|
[
{
"docid": "17930286",
"text": "OBJECTIVE To evaluate the association of overall and specific headaches with volume of white matter hyperintensities, brain infarcts, and cognition. DESIGN Population based, cross sectional study. SETTING Epidemiology of Vascular Ageing study, Nantes, France. PARTICIPANTS 780 participants (mean age 69, 58.5% women) with detailed headache assessment. MAIN OUTCOME MEASURES Brain scans were evaluated for volume of white matter hyperintensities (by fully automated imaging processing) and for classification of infarcts (by visual reading with a standardised assessment grid). Cognitive function was assessed by a battery of tests including the mini-mental state examination. RESULTS 163 (20.9%) participants reported a history of severe headache and 116 had migraine, of whom 17 (14.7%) reported aura symptoms. An association was found between any history of severe headache and increasing volume of white matter hyperintensities. The adjusted odds ratio of being in the highest third for total volume of white matter hyperintensities was 2.0 (95% confidence interval 1.3 to 3.1, P for trend 0.002) for participants with any history of severe headache when compared with participants without severe headache being in the lowest third. The association pattern was similar for all headache types. Migraine with aura was the only headache type strongly associated with volume of deep white matter hyperintensities (highest third odds ratio 12.4, 1.6 to 99.4, P for trend 0.005) and with brain infarcts (3.4, 1.2 to 9.3). The location of infarcts was predominantly outside the cerebellum and brain stem. Evidence was lacking for cognitive impairment for any headache type with or without brain lesions. CONCLUSIONS In this population based study, any history of severe headache was associated with an increased volume of white matter hyperintensities. Migraine with aura was the only headache type associated with brain infarcts. Evidence that headache of any type by itself or in combination with brain lesions was associated with cognitive impairment was lacking.",
"title": "Headache, migraine, and structural brain lesions and function: population based Epidemiology of Vascular Ageing-MRI study"
}
] |
[
{
"docid": "24865781",
"text": "Forty-one recurrent tension headache sufferers were randomly assigned to either cognitive-behavioral therapy (administered in a primarily home-based treatment protocol) or to amitriptyline therapy (with dosage individualized at 25, 50, or 75 mg/day). Cognitive-behavioral therapy and amitriptyline each yielded clinically significant improvements in headache activity, both when improvement was assessed with patient daily recordings (56% and 27% reduction in headache index, respectively), and when improvement was assessed with neurologist ratings of clinical improvement (94% and 69% of patients rated at least moderately improved, respectively). In instances where differences in treatment effectiveness were observed (headache index, somatic complaints, perceptions of control of headache activity), cognitive-behavioral therapy yielded somewhat more positive outcomes than did amitriptyline. Neither treatment, however, eliminated headache problems.",
"title": "A comparison of pharmacological (amitriptyline HCL) and nonpharmacological (cognitive-behavioral) therapies for chronic tension headaches."
},
{
"docid": "6191684",
"text": "CONTEXT Chronic tension-type headaches are characterized by near-daily headaches and often are difficult to manage in primary practice. Behavioral and pharmacological therapies each appear modestly effective, but data are lacking on their separate and combined effects. OBJECTIVE To evaluate the clinical efficacy of behavioral and pharmacological therapies, singly and combined, for chronic tension-type headaches. DESIGN AND SETTING Randomized placebo-controlled trial conducted from August 1995 to January 1998 at 2 outpatient sites in Ohio. PARTICIPANTS Two hundred three adults (mean age, 37 years; 76% women) with diagnosis of chronic tension-type headaches (mean, 26 headache d/mo). INTERVENTIONS Participants were randomly assigned to receive tricyclic antidepressant (amitriptyline hydrochloride, up to 100 mg/d, or nortriptyline hydrochloride, up to 75 mg/d) medication (n = 53), placebo (n = 48), stress management (eg, relaxation, cognitive coping) therapy (3 sessions and 2 telephone contacts) plus placebo (n = 49), or stress management therapy plus antidepressant medication (n = 53). MAIN OUTCOME MEASURES Monthly headache index scores calculated as the mean of pain ratings (0-10 scale) recorded by participants in a daily diary 4 times per day; number of days per month with at least moderate pain (pain rating >/=5), analgesic medication use, and Headache Disability Inventory scores, compared by intervention group. RESULTS Tricyclic antidepressant medication and stress management therapy each produced larger reductions in headache activity, analgesic medication use, and headache-related disability than placebo, but antidepressant medication yielded more rapid improvements in headache activity. Combined therapy was more likely to produce clinically significant (>/=50%) reductions in headache index scores (64% of participants) than antidepressant medication (38% of participants; P =.006), stress management therapy (35%; P =.003), or placebo (29%; P =.001). On other measures the combined therapy and its 2 component therapies produced similar outcomes. CONCLUSIONS Our results indicate that antidepressant medication and stress management therapy are each modestly effective in treating chronic tension-type headaches. Combined therapy may improve outcome relative to monotherapy.",
"title": "Management of chronic tension-type headache with tricyclic antidepressant medication, stress management therapy, and their combination: a randomized controlled trial."
},
{
"docid": "21274919",
"text": "OBJECTIVE Chronic physical comorbidity is common in dementia. However, there is an absence of evidence to support good practice guidelines for attention to these problems. We aimed to study the extent of this comorbidity and its impact on cognitive function and disability in population-based studies in low and middle income countries, where chronic diseases and impairments are likely to be both common and undertreated. METHODS A multicentre cross-sectional survey of all over 65 year old residents (n = 15 022) in 11 catchment areas in China, India, Cuba, Dominican Republic, Venezuela, Mexico and Peru. We estimated the prevalence of pain, incontinence, hearing and visual impairments, mobility impairment and undernutrition according to the presence of dementia and its severity, and, among those with dementia, the independent contribution of these impairments to cognitive function and disability, adjusting for age, gender, education and dementia severity. RESULTS Incontinence, hearing impairment, mobility impairment and undernutrition were consistently linearly associated with the presence of dementia and its severity across regions. Among people with dementia, incontinence, hearing impairment and mobility impairment were independently associated with disability in all regions while the contributions of pain, visual impairment and undernutrition were inconsistent. Only hearing impairment made a notable independent contribution to cognitive impairment. CONCLUSIONS There is an urgent need for clinical trials of the feasibility, efficacy and cost-effectiveness of regular physical health checks and remediation of identified pathologies, given the considerable comorbidity identified in our population based studies, and the strong evidence for independent impact upon functioning.",
"title": "The association between common physical impairments and dementia in low and middle income countries, and, among people with dementia, their association with cognitive function and disability. A 10/66 Dementia Research Group population-based study."
},
{
"docid": "24285403",
"text": "OBJECTIVES To determine whether the ankle brachial index (ABI, a marker of generalized atherosclerosis) is associated with cognitive impairment after 10 years in older people. DESIGN Cohort study (Edinburgh Artery Study). SETTING Eleven general practices in Edinburgh, Scotland. PARTICIPANTS Seven hundred seventeen men and women aged 55 to 74 from the general population, followed for 10 years. MEASUREMENTS ABI measured at baseline and major cognitive functions (including premorbid function using the National Adult Reading Test, NART) tested after 10 years. RESULTS After adjustment for age and sex, a low ABI was associated with lower scoring (bottom tertile vs top tertile) on Raven's Matrices (odds ratio (OR)=1.6, 95% confidence interval (CI) =1.0-2.6), Verbal Fluency (OR =1.8, 95% CI =1.1-3.0), and Digit Symbol Test (OR =2.3, 95% CI =1.3-4.2), suggesting that the ABI is predictive of poorer performance in nonverbal reasoning, verbal fluency, and information processing speed. The association between ABI and the Digit Symbol Test remained significant after further adjustment for premorbid cognitive function (tested using the NART), suggesting that the ABI is also predictive of decline in information processing speed (from premorbid ability to that measured here in older age). CONCLUSION The ABI may be useful in identifying older individuals at higher risk of cognitive impairment. In the future, preventive measures developed to target individuals with a low ABI should consider measures to reduce vascular-related cognitive decline as well as cardiovascular events, in an effort to reduce the incidence and consequences of subsequent cognitive impairment and dementia.",
"title": "Ankle brachial index as a predictor of cognitive impairment in the general population: ten-year follow-up of the Edinburgh Artery Study."
},
{
"docid": "12667988",
"text": "Twenty-seven migraine headache patients were divided into three equal groups which received thermal biofeedback, frontalis EMG biofeedback, or relaxation training. Training was given under \"massed\" practice conditions (nine sessions per week) and consisted of 18 training sessions and six test-generalisation sessions. While improvements in headaches were observed in all groups, the best improvements took place in the thermal biofeedback group, which had almost complete elimination of migraine attacks by the end of training, and maintained that performance as long as six months after training. Examination of the patterns of skin temperature and EMG changes in the three groups over the course of training also points to a relationship between skin temperature control and reduction in migraine headache symptomatology, and suggests that this relationship is worthy of further investigation.",
"title": "Biofeedback and relaxation in the treatment of migraine headaches: comparative effectiveness and physiological correlates."
},
{
"docid": "20471181",
"text": "Despite widespread use of antiretroviral therapies to control replication of the human immunodeficiency virus (HIV), dysfunctions of cognition that are collectively termed HIV-associated neurocognitive disorders (HAND) still occur in approximately 50% of those infected by the virus. Currently there is not a biomarker that can identify HIV-infected people who are at risk for the development of HAND. Previous studies have identified particular sphingolipid species that are dysregulated in HAND, but the neurocognitive correlates of these biochemical findings are not currently understood. To address this question, we compared cerebrospinal fluid (CSF) levels of sphingomyelin, ceramide, and sterol species with performance on standard neurological tests designed to assess the function of multiple cognitive and motor domains in HIV-infected subjects. We found that sphingomyelin:ceramide ratios for acyl chain lengths of C16∶0, C18∶0, C22∶0, and C24∶0 were associated with worse performance on several indices of memory. The most striking finding was for the acyl chain of C18∶0 that consistently associatedwith performance onmultiple tests of memory. These findings suggest that the sphingomyelin:ceramide ratio for C18∶0 may be a reasonable surrogate marker for memory dysfunction in HIV-infected subjects.",
"title": "Disturbance in cerebral spinal fluid sphingolipid content is associated with memory impairment in subjects infected with the human immunodeficiency virus"
},
{
"docid": "7997337",
"text": "There is mounting evidence showing that the structural and molecular organization of synaptic connections is affected both in human patients and in animal models of neurological and psychiatric diseases. As a consequence of these experimental observations, it has been introduced the concept of synapsopathies, a notion describing brain disorders of synaptic function and plasticity. A close correlation between neurological diseases and synaptic abnormalities is especially relevant for those syndromes including also mental retardation in their symptomatology, such as Rett syndrome (RS). RS (MIM312750) is an X-linked dominant neurological disorder that is caused in the majority of cases by mutations in methyl-CpG-binding protein 2 (MeCP2). This review will focus on the current knowledge of the synaptic alterations produced by mutations of the gene MeCP2 in mouse models of RS and will highlight prospects experimental therapies currently in use. Different experimental approaches have revealed that RS could be the consequence of an impairment in the homeostasis of synaptic transmission in specific brain regions. Indeed, several forms of experience-induced neuronal plasticity are impaired in the absence of MeCP2. Based on the results presented in this review, it is reasonable to propose that understanding how the brain is affected by diseases such as RS is at reach. This effort will bring us closer to identify the neurobiological bases of human cognition.",
"title": "Synaptic Determinants of Rett Syndrome"
},
{
"docid": "7239105",
"text": "Remarkable advances have been made in recent years towards therapeutics for cognitive impairment in individuals with Down syndrome (DS) by using mouse models. In this review, we briefly describe the phenotypes of mouse models that represent outcome targets for drug testing, the behavioral tests used to assess impairments in cognition and the known mechanisms of action of several drugs that are being used in preclinical studies or are likely to be tested in clinical trials. Overlaps in the distribution of targets and in the pathways that are affected by these diverse drugs in the trisomic brain suggest new avenues for DS research and drug development.",
"title": "The use of mouse models to understand and improve cognitive deficits in Down syndrome"
},
{
"docid": "10893238",
"text": "BACKGROUND Frail and dependent older people in resource-poor settings are poorly served by health systems that lack outreach capacity. The COPE (Caring for Older PEople) multidimensional assessment tool is designed to help community health workers (CHWs) identify clinically significant impairments and deliver evidence-based interventions METHODS Older people (n = 150) identified by CHWs as frail or dependent, were assessed at home by the CHW using the structured COPE assessment tool, generating information on impairments in nutrition, mobility, vision, hearing, continence, cognition, mood and behaviour. The older people were reassessed by local physicians who reached a clinical judgment regarding the presence or absence of the same impairments based upon clinical examination guided by the EASY-Care assessment tool. RESULTS The COPE tool was considered easy to administer, and gave CHWs a sense of empowerment to understand and act upon the needs of older people. Agreement between COPE assessment by CHW and clinician assessors was modest (ranged from 45.8 to 91.3 %) for most impairments. However, the prevalence of impairments was generally higher according to clinicians, particularly for visual impairment (98.7 vs 45.8 %), cognitive impairment (78.4 vs. 38.2 %) and depression (82.0 vs. 59.9 %). Most cases identified by WHO-COPE were clinician confirmed (positive predictive values - 72.2 to 98.5 %), and levels of disability and needs for care among those identified by COPE were higher than those additionally identified by the clinician alone. CONCLUSIONS The COPE is a feasible tool for the identification of specific impairments in frail dependent older people in the community. Those identified are likely to be confirmed as having clinically relevant problems by clinicians working in the same service, and the COPE may be particularly effective at targeting attention upon those with the most substantial unmet needs.",
"title": "Identifying common impairments in frail and dependent older people: validation of the COPE assessment for non-specialised health workers in low resource primary health care settings"
},
{
"docid": "5137019",
"text": "HIV-1 replication within macrophages of the CNS often results in cognitive and motor impairment, which is known as HIV-associated dementia (HAD) in its most severe form. IFN-beta suppresses viral replication within these cells during early CNS infection, but the effect is transient. HIV-1 eventually overcomes this protective innate immune response to resume replication through an unknown mechanism, initiating the progression toward HAD. In this article, we show that Suppressor of Cytokine Signaling (SOCS)3, a molecular inhibitor of IFN signaling, may allow HIV-1 to evade innate immunity within the CNS. We found that SOCS3 is elevated in an in vivo SIV/macaque model of HAD and that the pattern of expression correlates with recurrence of viral replication and onset of CNS disease. In vitro, the HIV-1 regulatory protein transactivator of transcription induces SOCS3 in human and murine macrophages in a NF-kappaB-dependent manner. SOCS3 expression attenuates the response of macrophages to IFN-beta at proximal levels of pathway activation and downstream antiviral gene expression and consequently overcomes the inhibitory effect of IFN-beta on HIV-1 replication. These studies indicate that SOCS3 expression, induced by stimuli present in the HIV-1-infected brain, such as transactivator of transcription, inhibits antiviral IFN-beta signaling to enhance HIV-1 replication in macrophages. This consequence of SOCS3 expression in vitro, supported by a correlation with increased viral load and onset of CNS disease in vivo, suggests that SOCS3 may allow HIV-1 to evade the protective innate immune response within the CNS, allowing the recurrence of viral replication and, ultimately, promoting progression toward HAD.",
"title": "Suppressor of cytokine signaling 3 inhibits antiviral IFN-beta signaling to enhance HIV-1 replication in macrophages."
},
{
"docid": "7965928",
"text": "IMPORTANCE Concussion and subconcussive impacts have been associated with short-term disrupted cognitive performance in collegiate athletes, but there are limited data on their long-term neuroanatomic and cognitive consequences. OBJECTIVE To assess the relationships of concussion history and years of football experience with hippocampal volume and cognitive performance in collegiate football athletes. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional study conducted between June 2011 and August 2013 at a US psychiatric research institute specializing in neuroimaging among collegiate football players with a history of clinician-diagnosed concussion (n = 25), collegiate football players without a history of concussion (n = 25), and non-football-playing, age-, sex-, and education-matched healthy controls (n = 25). EXPOSURES History of clinician-diagnosed concussion and years of football experience. MAIN OUTCOMES AND MEASURES High-resolution anatomical magnetic resonance imaging was used to quantify brain volumes. Baseline scores on a computerized concussion-related cognitive battery were used for cognitive assessment in athletes. RESULTS Players with and without a history of concussion had smaller hippocampal volumes relative to healthy control participants (with concussion: t48 = 7.58; P < .001; mean difference, 1788 μL; 95% CI, 1317-2258 μL; without concussion: t48 = 4.35; P < .001, mean difference, 1027 μL; 95% CI, 556-1498 μL). Players with a history of concussion had smaller hippocampal volumes than players without concussion (t48 = 3.15; P < .001; mean difference, 761 μL; 95% CI, 280-1242 μL). In both athlete groups, there was a statistically significant inverse relationship between left hippocampal volume and number of years of football played (t46 = -3.62; P < .001; coefficient = -43.54; 95% CI, -67.66 to -19.41). Behavioral testing demonstrated no differences between athletes with and without a concussion history on 5 cognitive measures but did show an inverse correlation between years of playing football and reaction time (ρ42 = -0.43; 95% CI, -0.46 to -0.40; P = .005). CONCLUSIONS AND RELEVANCE Among a group of collegiate football athletes, there was a significant inverse relationship of concussion and years of football played with hippocampal volume. Years of football experience also correlated with slower reaction time. Further research is needed to determine the temporal relationships of these findings.",
"title": "Relationship of collegiate football experience and concussion with hippocampal volume and cognitive outcomes."
},
{
"docid": "3202143",
"text": "Of all the age-related declines, memory loss is one of the most devastating. While conditions that increase longevity have been identified, the effects of these longevity-promoting factors on learning and memory are unknown. Here we show that the C. elegans Insulin/IGF-1 receptor mutant daf-2 improves memory performance early in adulthood and maintains learning ability better with age but, surprisingly, demonstrates no extension in long-term memory with age. By contrast, eat-2 mutants, a model of Dietary Restriction (DR), exhibit impaired long-term memory in young adulthood but maintain this level of memory longer with age. We find that crh-1, the C. elegans homolog of the CREB transcription factor, is required for long-term associative memory, but not for learning or short-term memory. The expression of crh-1 declines with age and differs in the longevity mutants, and CREB expression and activity correlate with memory performance. Our results suggest that specific longevity treatments have acute and long-term effects on cognitive functions that decline with age through their regulation of rate-limiting genes required for learning and memory.",
"title": "Insulin Signaling and Dietary Restriction Differentially Influence the Decline of Learning and Memory with Age"
},
{
"docid": "24510595",
"text": "PURPOSE Patients with daily or near-daily headaches are commonly seen in neurology practices and in headache subspecialty centers, but there is little information on the prevalence of this condition in the general population. We present the first US-based study describing the prevalence and characteristics of frequent headache in the general population. METHODS In Baltimore County, Maryland, 13 343 individuals 18 to 65 years of age were selected by random-digit dialing and interviewed by telephone about their headaches. Subjects reporting 180 or more headaches per year were classified as having frequent headache. Three mutually exclusive subtypes of frequent headache were identified: frequent headache with migrainous features, chronic tension-type headache, and unclassified frequent headache. RESULTS The overall prevalence of frequent headache was 4.1% (5.0% female, 2.8% male; 1.8:1 female to male ratio). Frequent headache was 33% more common in Caucasians (4.4%) than in African Americans (3.3%). In both males and females, prevalence was highest in the lowest educational category. Among frequent headache sufferers, more than half (52% female, 56% male) met criteria for chronic tension-type headache, almost one third (33% female, 25% male) met criteria for frequent headache with migrainous features, and the remainder (15% female, 19% male) were unclassified. Overall, 30% of female and 25% of male frequent headache sufferers met International Headache Society (IHS) criteria for migraine (with or without aura). CONCLUSIONS Frequent headache is common in the general population and is more prevalent in Caucasians and in those with less than a high school education. Chronic tension-type headache is more common than frequent headache with migrainous features, though the latter is more disabling. Although more common in females than males, the female preponderance of frequent headache is less marked than in migraine. The sex ratio varies by frequent headache subtype.",
"title": "Prevalence of frequent headache in a population sample."
},
{
"docid": "14079881",
"text": "OBJECTIVE To determine whether perceived age correlates with survival and important age related phenotypes. DESIGN Follow-up study, with survival of twins determined up to January 2008, by which time 675 (37%) had died. SETTING Population based twin cohort in Denmark. PARTICIPANTS 20 nurses, 10 young men, and 11 older women (assessors); 1826 twins aged >or=70. MAIN OUTCOME MEASURES Assessors: perceived age of twins from photographs. Twins: physical and cognitive tests and molecular biomarker of ageing (leucocyte telomere length). RESULTS For all three groups of assessors, perceived age was significantly associated with survival, even after adjustment for chronological age, sex, and rearing environment. Perceived age was still significantly associated with survival after further adjustment for physical and cognitive functioning. The likelihood that the older looking twin of the pair died first increased with increasing discordance in perceived age within the twin pair-that is, the bigger the difference in perceived age within the pair, the more likely that the older looking twin died first. Twin analyses suggested that common genetic factors influence both perceived age and survival. Perceived age, controlled for chronological age and sex, also correlated significantly with physical and cognitive functioning as well as with leucocyte telomere length. CONCLUSION Perceived age-which is widely used by clinicians as a general indication of a patient's health-is a robust biomarker of ageing that predicts survival among those aged >or=70 and correlates with important functional and molecular ageing phenotypes.",
"title": "Perceived age as clinically useful biomarker of ageing: cohort study."
},
{
"docid": "14606752",
"text": "OBJECTIVE To evaluate the efficacy and relative adverse effects of tricyclic antidepressants in the treatment of migraine, tension-type, and mixed headaches. DESIGN Meta-analysis. DATA SOURCES Medline, Embase, the Cochrane Trials Registry, and PsycLIT. Studies reviewed Randomised trials of adults receiving tricyclics as only treatment for a minimum of four weeks. DATA EXTRACTION Frequency of headaches (number of headache attacks for migraine and number of days with headache for tension-type headaches), intensity of headache, and headache index. RESULTS 37 studies met the inclusion criteria. Tricyclics significantly reduced the number of days with tension-type headache and number of headache attacks from migraine than placebo (average standardised mean difference -1.29, 95% confidence interval -2.18 to -0.39 and -0.70, -0.93 to -0.48) but not compared with selective serotonin reuptake inhibitors (-0.80, -2.63 to 0.02 and -0.20, -0.60 to 0.19). The effect of tricyclics increased with longer duration of treatment (β=-0.11, 95% confidence interval -0.63 to -0.15; P<0.0005). Tricyclics were also more likely to reduce the intensity of headaches by at least 50% than either placebo (tension-type: relative risk 1.41, 95% confidence interval 1.02 to 1.89; migraine: 1.80, 1.24 to 2.62) or selective serotonin reuptake inhibitors (1.73, 1.34 to 2.22 and 1.72, 1.15 to 2.55). Tricyclics were more likely to cause adverse effects than placebo (1.53, 95% confidence interval 1.11 to 2.12) and selective serotonin reuptake inhibitors (2.22, 1.52 to 3.32), including dry mouth (P<0.0005 for both), drowsiness (P<0.0005 for both), and weight gain (P<0.001 for both), but did not increase dropout rates (placebo: 1.22, 0.83 to 1.80, selective serotonin reuptake inhibitors: 1.16, 0.81 to 2.97). CONCLUSIONS Tricyclic antidepressants are effective in preventing migraine and tension-type headaches and are more effective than selective serotonin reuptake inhibitors, although with greater adverse effects. The effectiveness of tricyclics seems to increase over time.",
"title": "Tricyclic antidepressants and headaches: systematic review and meta-analysis"
},
{
"docid": "44830890",
"text": "OBJECTIVE To investigate the frequency of depressive and anxiety disorders in patients with chronic daily headache. BACKGROUND There is a lack of data in the literature on the extent of psychiatric comorbidity in patients with different subtypes of chronic daily headache. METHODS We recruited consecutive patients with chronic daily headache seen in a headache clinic from November 1998 to December 1999. The subtypes of chronic daily headache were classified according to the criteria proposed by Silberstein et al. A psychiatrist evaluated the patients according to the structured Mini-International Neuropsychiatric Interview to assess the comorbidity of depressive and anxiety disorders. RESULTS Two hundred sixty-one patients with chronic daily headache were recruited. The mean age was 46 years, and 80% were women. Transformed migraine was diagnosed in 152 patients (58%) and chronic tension-type headache in 92 patients (35%). Seventy-eight percent of patients with transformed migraine had psychiatric comorbidity, including major depression (57%), dysthymia (11%), panic disorder (30%), and generalized anxiety disorder (8%). Sixty-four percent of patients with chronic tension-type headache had psychiatric diagnoses, including major depression (51%), dysthymia (8%), panic disorder (22%), and generalized anxiety disorder (1%). The frequency of anxiety disorders was significantly higher in patients with transformed migraine after controlling for age and sex (P =.02). Both depressive and anxiety disorders were significantly more frequent in women. CONCLUSION Psychiatric comorbidity, especially major depression and panic disorders, was highly prevalent in patients with chronic daily headache seen in a headache clinic. These results demonstrate that women and patients with transformed migraine are at higher risk of psychiatric comorbidity.",
"title": "Comorbidity of depressive and anxiety disorders in chronic daily headache and its subtypes."
},
{
"docid": "22995579",
"text": "The tricyclic antidepressant, amitriptyline, is an effective drug for the treatment of chronic tension-type headache and for other chronic pain syndromes, but it is also effective in the prophylaxis of an episodic type of headache such as migraine. However, its efficacy in episodic tension-type headache has not yet been clarified. We compared the efficacy of amitriptyline (25 mg/day) in 82 nondepressed patients with either chronic or episodic tension-type headache in an open-label study. Amitriptyline significantly reduced (P < 0.05) frequency and duration of headache as well as analgesic consumption in chronic, but not in episodic, tension-type headache. Further placebo-controlled trials, possibly with higher doses of amitriptyline, might confirm if the different pattern of response to amitriptyline can be explained in terms of different involvement of central nociception and of peripheral myofascial factors in the chronic and in the episodic forms of tension-type headache.",
"title": "Amitriptyline is effective in chronic but not in episodic tension-type headache: pathogenetic implications."
},
{
"docid": "23865182",
"text": "Amitriptyline is the medication of first choice in the treatment of chronic tension-type headache. In 197 patients with chronic tension-type headache (87M and 110F with a mean age of 38 +/- 13 (18-68)) efficacy and tolerability of 60-90 mg amitriptylinoxide (AO) were compared with 50-75 mg amitriptyline (AM) and placebo (PL) in a double-blind, parallel-group trial consisting of a four weeks' baseline phase and 12 weeks of treatment. The primary study endpoint was a reduction of at least 50% of the product of headache duration and frequency and a reduction of at least 50% in headache intensity. Statistics used were Fisher's exact test and analysis of variance. No significant difference emerged between AO, AM and PL with respect to the primary study endpoint. Treatment response occurred in 30.3% of the AO, 22.4% of the AM and 21.9% of the PL group. A reduction in headache duration and frequency of at least 50% was found in 39.4% on AO, in 25.4% on AM and in 26.6% on PL (PAO-PL = .1384, PAM-PL = 1.000, PAO-AM = .0973). A reduction in headache intensity of at least 50% was found in 31.8% on AO, in 26.9% on AM and in 26.6% on PL (PAO-PL = .5657, PAM-PL = 1.000, PAO-AM = .5715). Trend analysis with respect to a significant reduction of headache intensity (p < 0.05) and the product of headache duration and frequency revealed a superior effect of AO.(ABSTRACT TRUNCATED AT 250 WORDS)",
"title": "Efficacy and tolerability of amitriptylinoxide in the treatment of chronic tension-type headache: a multi-centre controlled study."
},
{
"docid": "1642727",
"text": "CONTEXT Many observational studies have shown that physical activity reduces the risk of cognitive decline; however, evidence from randomized trials is lacking. OBJECTIVE To determine whether physical activity reduces the rate of cognitive decline among older adults at risk. DESIGN AND SETTING Randomized controlled trial of a 24-week physical activity intervention conducted between 2004 and 2007 in metropolitan Perth, Western Australia. Assessors of cognitive function were blinded to group membership. PARTICIPANTS We recruited volunteers who reported memory problems but did not meet criteria for dementia. Three hundred eleven individuals aged 50 years or older were screened for eligibility, 89 were not eligible, and 52 refused to participate. A total of 170 participants were randomized and 138 participants completed the 18-month assessment. INTERVENTION Participants were randomly allocated to an education and usual care group or to a 24-week home-based program of physical activity. MAIN OUTCOME MEASURE Change in Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores (possible range, 0-70) over 18 months. RESULTS In an intent-to-treat analysis, participants in the intervention group improved 0.26 points (95% confidence interval, -0.89 to 0.54) and those in the usual care group deteriorated 1.04 points (95% confidence interval, 0.32 to 1.82) on the ADAS-Cog at the end of the intervention. The absolute difference of the outcome measure between the intervention and control groups was -1.3 points (95% confidence interval,-2.38 to -0.22) at the end of the intervention. At 18 months, participants in the intervention group improved 0.73 points (95% confidence interval, -1.27 to 0.03) on the ADAS-Cog, and those in the usual care group improved 0.04 points (95% confidence interval, -0.46 to 0.88). Word list delayed recall and Clinical Dementia Rating sum of boxes improved modestly as well, whereas word list total immediate recall, digit symbol coding, verbal fluency, Beck depression score, and Medical Outcomes 36-Item Short-Form physical and mental component summaries did not change significantly. CONCLUSIONS In this study of adults with subjective memory impairment, a 6-month program of physical activity provided a modest improvement in cognition over an 18-month follow-up period. TRIAL REGISTRATION anzctr.org.au Identifier: ACTRN12605000136606.",
"title": "Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease: a randomized trial."
},
{
"docid": "41735503",
"text": "A set of related medical disorders that lack a proper classification system and diagnostic criteria is like a society without laws. The result is incoherence at best, chaos at worst. For this reason, the International Classification of Headache Disorders (ICHD) is arguably the single most important breakthrough in headache medicine over the last 50 years. The ICHD identifies and categorizes more than a hundred different kinds of headache in a logical, hierarchal system. Even more important, it has provided explicit diagnostic criteria for all of the headache disorders listed. The ICHD quickly became universally accepted, and criticism of the classification has been minor relative to that directed at other disease classification systems. Over the 20 years following publication of the first edition of the ICHD, headache research has rapidly accelerated despite sparse allocation of resources to that effort. In summary, the ICHD has attained widespread acceptance at the international level and has substantially facilitated both clinical research and clinical care in the field of headache medicine.",
"title": "The International Classification of Headache Disorders."
},
{
"docid": "24055603",
"text": "Thirty patients with tension-type headache were randomly chosen to undergo a trial of traditional Chinese acupuncture and sham acupuncture. Five measures were used to assess symptom severity and treatment response: intensity, duration and frequency of headache pain episodes, headache index and analgesic intake. The five measures were assessed during a 4 week baseline period, after 4 and 8 weeks of treatment, and 1, 6 and 12 months thereafter. Before the start of the study, each patient was administered the MMPI. Split-plot ANOVAs showed that, compared to baseline, at 1 month after the end of treatment and for the 12 month follow-up, the frequency of headache episodes, analgesic consumption and the headache index (but not the duration or intensity of headache episodes) significantly decreased over time; however, no difference between acupuncture and placebo treatment was found. No single MMPI scale predicted the response to treatment, but the mean MMPI profile of acupuncture non-responders showed the presence of 'Conversion V'.",
"title": "Traditional Chinese acupuncture in tension-type headache: a controlled study."
},
{
"docid": "12899460",
"text": "BACKGROUND The Euro-D depression scale consists of symptom clusters that may be differentially related to demographic and cognitive characteristics in older adults. This hypothesis needs further investigation and the role of measurement bias on substantive conclusions remains to be established. METHOD The study sample comprised 10,405 community-dwelling older adults from six Latin American countries. We applied a Multiple Indicators Multiple Causes (MIMIC) model for a concurrent investigation of measurement bias and of the association between Euro-D symptom clusters and background variables. RESULTS The factorial validity of Euro-D, with a two-dimensional structure--affective suffering and motivation disturbance, was consistently supported in all countries. Although complete measurement invariance could not be assumed across countries, measurement bias was minor. Both Euro-D factors were unrelated to age, but related to gender, as well as to impairment in memory and verbal fluency. Gender differences were larger for affective suffering than for motivation disturbance, whereas differences in verbal fluency impairment were more strongly related to motivation disturbance. LIMITATIONS Our analytic strategies could only examine invariance at the level of indicator thresholds. The generalisability of current findings needs to be examined in clinical populations. A wider set of cognitive tests is needed. We did not examine the compositional factors that could have accounted for the variation in Euro-D scores across countries, as this was beyond the aims of the paper. CONCLUSION The current study adds evidence for the construct validity of Euro-D and for the possible differential association of depression symptom-clusters with gender and verbal fluency in older adults. An understanding of the heterogeneity of late-life depression may carry clinical implications for the diagnosis and treatment of depression in old age.",
"title": "A multiple indicators multiple causes model of late-life depression in Latin American countries"
},
{
"docid": "10190462",
"text": "Background: Reduced brain insulin signaling and low CSF-to-plasma insulin ratios have been observed in patients with Alzheimer disease (AD). Furthermore, intracerebroventricular or IV insulin administration improve memory, alter evoked potentials, and modulate neurotransmitters, possibly by augmenting low brain levels. After intranasal administration, insulin-like peptides follow extracellular pathways to the brain within 15 minutes. Objective: We tested the hypothesis that daily intranasal insulin treatment would facilitate cognition in patients with early AD or its prodrome, amnestic mild cognitive impairment (MCI). The proportion of verbal information retained after a delay period was the planned primary outcome measure. Secondary outcome measures included attention, caregiver rating of functional status, and plasma levels of insulin, glucose, β-amyloid, and cortisol. Methods: Twenty-five participants were randomly assigned to receive either placebo (n = 12) or 20 IU BID intranasal insulin treatment (n = 13) using an electronic atomizer, and 24 participants completed the study. Participants, caregivers, and all clinical evaluators were blinded to treatment assignment. Cognitive measures and blood were obtained at baseline and after 21 days of treatment. Results: Fasting plasma glucose and insulin were unchanged with treatment. The insulin-treated group retained more verbal information after a delay compared with the placebo-assigned group ( p = 0.0374). Insulin-treated subjects also showed improved attention ( p = 0.0108) and functional status ( p = 0.0410). Insulin treatment raised fasting plasma concentrations of the short form of the β-amyloid peptide (Aβ40; p = 0.0471) without affecting the longer isoform (Aβ42), resulting in an increased Aβ40/42 ratio ( p = 0.0207). Conclusions: The results of this pilot study support further investigation of the benefits of intranasal insulin for patients with Alzheimer disease, and suggest that intranasal peptide administration may be a novel approach to the treatment of neurodegenerative disorders.",
"title": "INTRANASAL INSULIN IMPROVES COGNITION AND MODULATES β-AMYLOID IN EARLY AD"
},
{
"docid": "39985001",
"text": "We retrospectively studied the long-term (2-year) outcome of 50 consecutive patients admitted to our inpatient headache program because of chronic daily headache (CDH) associated with the overuse of analgesics, ergotamine, or both. They had been detoxified, given repetitive intravenous dihydroergotamine (IV DHE) and prophylactic medications as part of the program, and had become headache-free on this regimen. At the time of admission, 37 of the 50 patients had transformed migraine (TM), 12 had new daily persistent headache (NDPH), and 1 had chronic tension-type headache; 29 of the patients with TM, 7 of those with NDPH, and the single patient with chronic tension-type headache had coexistent migraine. Substances abused, alone or in combination, included: caffeine in 39 patients (av. 441 mg/d), acetaminophen in 32 (av. 2187 mg/d), aspirin in 24 (av. 1807 mg/d), ibuprofen in 9 (av. 1156 mg/d), narcotics in 7 (av. 10.1 mg morphine equivalents/d) and ergotamine in 11 (av. 2.3 mg/d). Twenty patients were using preventive medication at the time of admission. Follow-up evaluations were performed at 3, 6, 12, and 24 months after discharge. Forty-three patients were analyzed at 3 months. Of these, 44% had an excellent or good result and 28% a fair result; 3 were overusing analgesics. At 24 months, 39 patients were analyzed: 59% had a good or excellent result and 28% a fair result; 5 were overusing analgesics, 4 of whom were doing poorly.(ABSTRACT TRUNCATED AT 250 WORDS)",
"title": "Chronic daily headache: long-term prognosis following inpatient treatment with repetitive IV DHE."
},
{
"docid": "72372925",
"text": "There has never been a book on headache that came close to that of the late Harold Wolff. The second edition was published 10 years ago; it was and is a masterpiece of writing, an exhaustive yet engrossing delineation of Wolff's long study and understanding of headache. The new edition, revised by Dalessio, serves to bring certain aspects of headache up to date, most of them having to do with drug therapy. The emphasis on total therapy rather than simply drug therapy has been preserved, however. Dalessio has altered slightly the form of the book, although the \"new chapters\" on cluster headache and trigeminal neuralgia are merely transplants from other sections of the original. Migraine, the main part of the book, has been reshaped, with some anecdotal portions removed, but little has been added. It is of interest that nothing in the section on observations of methysergide (UML-491 in Wolff's",
"title": "Wolff's Headache and Other Head Pain."
},
{
"docid": "8570317",
"text": "We conducted a two-stage population-based headache survey among subjects aged > or = 15 in Taipei, Taiwan. Subjects with chronic daily headache (CDH) in the past year were identified, interviewed and followed-up. CDH was defined as a headache frequency > 15 days/month, with a duration > 4 h/day. Of the 3377 participants, 108 (3.2%) fulfilled the criteria for CDH, with a higher prevalence in women (4.3%) than men (1.9%). TM was the most common subtype (55%), followed by CTTH (44%). Thirty-four per cent of the CDH subjects overused analgesics. At the 2-year follow-up, 35% of the CDH subjects still had CDH. The significant predictors for persistent CDH at follow-up included: older age ( > or = 40 years) (RR = 2.4), CDH onset after 32 years (RR = 1.8), CDH duration > or = 6 years (RR = 2.0), medication overuse (RR = 1.8), and \"daily\" headache (RR = 2.1). We found that CDH is not uncommon in the community and its prevalence is similar among different populations. Older subjects and those with medication overuse may have a more protracted course of illness.",
"title": "Chronic daily headache in Taipei, Taiwan: prevalence, follow-up and outcome predictors."
},
{
"docid": "32743723",
"text": "We examined six patients with an abrupt change in behavior after infarction involving the inferior genu of the internal capsule. The acute syndrome featured fluctuating alertness, inattention, memory loss, apathy, abulia, and psychomotor retardation, suggesting frontal lobe dysfunction. Contralateral hemiparesis and dysarthria were generally mild, except when the infarct extended into the posterior limb. Neuropsychological testing in five patients with left-sided infarcts revealed severe verbal memory loss. Additional cognitive deficits consistent with dementia occurred in four patients. A right-sided infarct caused transient impairment in visuospatial memory. Functional brain imaging in three patients showed a focal reduction in hemispheric perfusion most prominent in the ipsilateral inferior and medial frontal cortex. We infer that the capsular genu infarct interrupted the inferior and anterior thalamic peduncles, resulting in functional deactivation of the ipsilateral frontal cortex. These observations suggest that one mechanism for cognitive deterioration from a lacunar infarct is thalamocortical disconnection of white-matter tracts, in some instances leading to \"strategic-infarct dementia. \"",
"title": "Confusion and memory loss from capsular genu infarction: a thalamocortical disconnection syndrome?"
},
{
"docid": "24770122",
"text": "To assess the clinical and personality characteristics of patients with chronic daily headache before and after treatment, 20 patients were examined and the Minnesota Multiphasic Personality Inventory (MMPI [Italian 356-item abbreviated version]) and the Strait and Trait Anxiety Index 1,2 (STAI) administered. There were two groups: group 1 (n = 6), with a \"conversion V\" configuration (with elevation of hypochondria and hysteria scales, the depression scale being somewhat lower); and group 2 (n = 13) with elevation of depression and of other MMPI scales. One patient had no scale elevation. STAI 1,2 scores were high in both groups. Several psychosomatic symptoms and some migraine features were present in almost all patients. Occurrence, severity, and duration of headache were recorded regularly and the MMPI and the STAI administered again after treatment. Improvement of headaches and a decrease of several MMPI and STAI 2 scores were observed. However, 12 of 20 patients showed a conversion V configuration after treatment. It is concluded that chronic daily headache was transformed migraine in most cases and was accompanied by anxiety levels in all patients and hysteric traits in some. With time, these patients may develop a depressive disorder. After treatment, hysterical traits are still present at a lower level in those showing these traits before treatment and may be unmasked in those that had depression.",
"title": "Chronic daily headache. A clinical and psychological profile before and after treatment."
},
{
"docid": "4407385",
"text": "Memory function often declines with age, and is believed to deteriorate initially because of changes in synaptic function rather than loss of neurons. Some individuals then go on to develop Alzheimer's disease with neurodegeneration. Here we use Tg2576 mice, which express a human amyloid-β precursor protein (APP) variant linked to Alzheimer's disease, to investigate the cause of memory decline in the absence of neurodegeneration or amyloid-β protein amyloidosis. Young Tg2576 mice (< 6 months old) have normal memory and lack neuropathology, middle-aged mice (6–14 months old) develop memory deficits without neuronal loss, and old mice (> 14 months old) form abundant neuritic plaques containing amyloid-β (refs 3–6). We found that memory deficits in middle-aged Tg2576 mice are caused by the extracellular accumulation of a 56-kDa soluble amyloid-β assembly, which we term Aβ*56 (Aβ star 56). Aβ*56 purified from the brains of impaired Tg2576 mice disrupts memory when administered to young rats. We propose that Aβ*56 impairs memory independently of plaques or neuronal loss, and may contribute to cognitive deficits associated with Alzheimer's disease.",
"title": "A specific amyloid-β protein assembly in the brain impairs memory"
},
{
"docid": "28419824",
"text": "Two hundred patients who were taking daily symptomatic or immediate relief medications, often in excessive quantities, yet suffering from daily or near daily severe headaches were studied. One hundred and sixteen (58%) of them were also taking concomitant prophylactic medications and they were ineffective. Low tyramine, low caffeine dietary instructions and biofeedback training were given to all patients. The effect of continuing symptomatic medications, discontinuing symptomatic medications, and adding or changing prophylactic medications were studied in the various treatment groups. It is concluded that; 1.) Daily use of symptomatic or immediate relief medications result in chronic daily headache. 2.) Discontinuing daily symptomatic medications itself result in improvement of headache. 3.) Concomitant use of symptomatic medications nullifies the effect of prophylactic medications. 4.) Discontinuing daily symptomatic medications enhances the beneficial effect of prophylactic medications.",
"title": "Drug induced refractory headache--clinical features and management."
}
] |
86
|
Adult tissue-resident macrophages are seeded before birth.
|
[
{
"docid": "22406695",
"text": "Macrophages are distributed in tissues throughout the body and contribute to both homeostasis and disease. Recently, it has become evident that most adult tissue macrophages originate during embryonic development and not from circulating monocytes. Each tissue has its own composition of embryonically derived and adult-derived macrophages, but it is unclear whether macrophages of distinct origins are functionally interchangeable or have unique roles at steady state. This new understanding also prompts reconsideration of the function of circulating monocytes. Classical Ly6c(hi) monocytes patrol the extravascular space in resting organs, and Ly6c(lo) nonclassical monocytes patrol the vasculature. Inflammation triggers monocytes to differentiate into macrophages, but whether resident and newly recruited macrophages possess similar functions during inflammation is unclear. Here, we define the tools used for identifying the complex origin of tissue macrophages and discuss the relative contributions of tissue niche versus ontological origin to the regulation of macrophage functions during steady state and inflammation.",
"title": "Origin and functions of tissue macrophages."
},
{
"docid": "7521113",
"text": "Mononuclear phagocytes, including monocytes, macrophages, and dendritic cells, contribute to tissue integrity as well as to innate and adaptive immune defense. Emerging evidence for labor division indicates that manipulation of these cells could bear therapeutic potential. However, specific ontogenies of individual populations and the overall functional organization of this cellular network are not well defined. Here we report a fate-mapping study of the murine monocyte and macrophage compartment taking advantage of constitutive and conditional CX(3)CR1 promoter-driven Cre recombinase expression. We have demonstrated that major tissue-resident macrophage populations, including liver Kupffer cells and lung alveolar, splenic, and peritoneal macrophages, are established prior to birth and maintain themselves subsequently during adulthood independent of replenishment by blood monocytes. Furthermore, we have established that short-lived Ly6C(+) monocytes constitute obligatory steady-state precursors of blood-resident Ly6C(-) cells and that the abundance of Ly6C(+) blood monocytes dynamically controls the circulation lifespan of their progeny.",
"title": "Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis."
}
] |
[
{
"docid": "2604063",
"text": "The intestinal microbiota has become a relevant aspect of human health. Microbial colonization runs in parallel with immune system maturation and plays a role in intestinal physiology and regulation. Increasing evidence on early microbial contact suggest that human intestinal microbiota is seeded before birth. Maternal microbiota forms the first microbial inoculum, and from birth, the microbial diversity increases and converges toward an adult-like microbiota by the end of the first 3-5 years of life. Perinatal factors such as mode of delivery, diet, genetics, and intestinal mucin glycosylation all contribute to influence microbial colonization. Once established, the composition of the gut microbiota is relatively stable throughout adult life, but can be altered as a result of bacterial infections, antibiotic treatment, lifestyle, surgical, and a long-term change in diet. Shifts in this complex microbial system have been reported to increase the risk of disease. Therefore, an adequate establishment of microbiota and its maintenance throughout life would reduce the risk of disease in early and late life. This review discusses recent studies on the early colonization and factors influencing this process which impact on health.",
"title": "The composition of the gut microbiota throughout life, with an emphasis on early life"
},
{
"docid": "12827098",
"text": "Despite accumulating evidence suggesting local self-maintenance of tissue macrophages in the steady state, the dogma remains that tissue macrophages derive from monocytes. Using parabiosis and fate-mapping approaches, we confirmed that monocytes do not show significant contribution to tissue macrophages in the steady state. Similarly, we found that after depletion of lung macrophages, the majority of repopulation occurred by stochastic cellular proliferation in situ in a macrophage colony-stimulating factor (M-Csf)- and granulocyte macrophage (GM)-CSF-dependent manner but independently of interleukin-4. We also found that after bone marrow transplantation, host macrophages retained the capacity to expand when the development of donor macrophages was compromised. Expansion of host macrophages was functional and prevented the development of alveolar proteinosis in mice transplanted with GM-Csf-receptor-deficient progenitors. Collectively, these results indicate that tissue-resident macrophages and circulating monocytes should be classified as mononuclear phagocyte lineages that are independently maintained in the steady state.",
"title": "Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes."
},
{
"docid": "22973574",
"text": "Macrophages and dendritic cells (DCs) are key components of cellular immunity and are thought to originate and renew from hematopoietic stem cells (HSCs). However, some macrophages develop in the embryo before the appearance of definitive HSCs. We thus reinvestigated macrophage development. We found that the transcription factor Myb was required for development of HSCs and all CD11b(high) monocytes and macrophages, but was dispensable for yolk sac (YS) macrophages and for the development of YS-derived F4/80(bright) macrophages in several tissues, such as liver Kupffer cells, epidermal Langerhans cells, and microglia--cell populations that all can persist in adult mice independently of HSCs. These results define a lineage of tissue macrophages that derive from the YS and are genetically distinct from HSC progeny.",
"title": "A lineage of myeloid cells independent of Myb and hematopoietic stem cells."
},
{
"docid": "16863359",
"text": "Inflammasomes are multiprotein complexes that link pathogen recognition and cellular stress to the processing of the proinflammatory cytokine interleukin-1β (IL-1β). Whereas inflammasome-mediated activation is heavily studied in hematopoietic macrophages and dendritic cells, much less is known about microglia, resident tissue macrophages of the brain that originate from a distinct progenitor. To directly compare inflammasome-mediated activation in different types of macrophages, we isolated primary microglia and hematopoietic macrophages from adult, healthy rhesus macaques. We analyzed the expression profile of NOD (nucleotide-binding oligomerization domain)-like receptors, adaptor proteins, and caspases and characterized inflammasome activation and regulation in detail. We here demonstrate that primary microglia can respond to the same innate stimuli as hematopoietic macrophages. However, microglial responses are more persistent due to lack of negative regulation on pro-IL-1β expression. In addition, we show that while caspase 1, 4, and 5 activation is pivotal for inflammasome-induced IL-1β secretion by hematopoietic macrophages, microglial secretion of IL-1β is only partially dependent on these inflammatory caspases. These results identify key cell type-specific differences that may aid the development of strategies to modulate innate immune responses in the brain.",
"title": "Inflammasome-induced IL-1β secretion in microglia is characterized by delayed kinetics and is only partially dependent on inflammatory caspases."
},
{
"docid": "12966719",
"text": "CD8 tissue-resident memory T (TRM) cells provide efficient local control of viral infection, but the role of CD4 TRM is less clear. Here, by using parabiotic mice, we show that a preexisting pool of CD4 TRM cells in the genital mucosa was required for full protection from a lethal herpes simplex virus 2 (HSV-2) infection. Chemokines secreted by a local network of macrophages maintained vaginal CD4 TRM in memory lymphocyte clusters (MLCs), independently of circulating memory T cells. CD4 TRM cells within the MLCs were enriched in clones that expanded in response to HSV-2. Our results highlight the need for vaccine strategies that enable establishment of TRM cells for protection from a sexually transmitted virus and provide insights as to how such a pool might be established.",
"title": "A local macrophage chemokine network sustains protective tissue-resident memory CD4 T cells"
},
{
"docid": "43192375",
"text": "Adipose tissue macrophages (ATMs) infiltrate adipose tissue during obesity and contribute to insulin resistance. We hypothesized that macrophages migrating to adipose tissue upon high-fat feeding may differ from those that reside there under normal diet conditions. To this end, we found a novel F4/80(+)CD11c(+) population of ATMs in adipose tissue of obese mice that was not seen in lean mice. ATMs from lean mice expressed many genes characteristic of M2 or \"alternatively activated\" macrophages, including Ym1, arginase 1, and Il10. Diet-induced obesity decreased expression of these genes in ATMs while increasing expression of genes such as those encoding TNF-alpha and iNOS that are characteristic of M1 or \"classically activated\" macrophages. Interestingly, ATMs from obese C-C motif chemokine receptor 2-KO (Ccr2-KO) mice express M2 markers at levels similar to those from lean mice. The antiinflammatory cytokine IL-10, which was overexpressed in ATMs from lean mice, protected adipocytes from TNF-alpha-induced insulin resistance. Thus, diet-induced obesity leads to a shift in the activation state of ATMs from an M2-polarized state in lean animals that may protect adipocytes from inflammation to an M1 proinflammatory state that contributes to insulin resistance.",
"title": "Obesity induces a phenotypic switch in adipose tissue macrophage polarization."
},
{
"docid": "4928057",
"text": "Organ-specific functions of tissue-resident macrophages in the steady-state heart are unknown. Here, we show that cardiac macrophages facilitate electrical conduction through the distal atrioventricular node, where conducting cells densely intersperse with elongated macrophages expressing connexin 43. When coupled to spontaneously beating cardiomyocytes via connexin-43-containing gap junctions, cardiac macrophages have a negative resting membrane potential and depolarize in synchrony with cardiomyocytes. Conversely, macrophages render the resting membrane potential of cardiomyocytes more positive and, according to computational modeling, accelerate their repolarization. Photostimulation of channelrhodopsin-2-expressing macrophages improves atrioventricular conduction, whereas conditional deletion of connexin 43 in macrophages and congenital lack of macrophages delay atrioventricular conduction. In the Cd11bDTR mouse, macrophage ablation induces progressive atrioventricular block. These observations implicate macrophages in normal and aberrant cardiac conduction.",
"title": "Macrophages Facilitate Electrical Conduction in the Heart"
},
{
"docid": "25068298",
"text": "Distribution and fine structure of macrophages were studied in 10 human embryos in the 6th and 7th week of gestation, 5.5 to 12 mm in crown-rump length. The yolk sac macrophages were found in the extravascular mesenchymal tissues and intravascular spaces long before the first appearance of bone marrow and lymphatic tissues in the embryos. In addition to the macrophages, the fibroblastic cells and the cells of erythropoietic series were also present in the extravascular space. The macrophages showed a variety of cellular structures suggesting transition from immature cell type with no heterophagolysosomes to mature cell type in phagocytosis. The mature macrophages avidly phagocytized the primitive erythroblasts and occasionally platelets. They were positively stained for lysosomal enzymes and were characterized by numerous pleomorphic heterophagolysosomes which exhibited various stages of digestion of phagocytized blood cells. The origin of intravascular macrophages may be in either migrated extravascular macrophages or phagocytic endothelial cells. The phagocytosis and degradation of erythroblasts appear to be one of the main functions of yolk sac macrophages. The presence of the macrophages in mitosis indicates their proliferation in situ.",
"title": "Electron microscopic studies of macrophages in early human yolk sacs."
},
{
"docid": "7489663",
"text": "A current paradigm states that monocytes circulate freely and patrol blood vessels but differentiate irreversibly into dendritic cells (DCs) or macrophages upon tissue entry. Here we show that bona fide undifferentiated monocytes reside in the spleen and outnumber their equivalents in circulation. The reservoir monocytes assemble in clusters in the cords of the subcapsular red pulp and are distinct from macrophages and DCs. In response to ischemic myocardial injury, splenic monocytes increase their motility, exit the spleen en masse, accumulate in injured tissue, and participate in wound healing. These observations uncover a role for the spleen as a site for storage and rapid deployment of monocytes and identify splenic monocytes as a resource that the body exploits to regulate inflammation.",
"title": "Identification of splenic reservoir monocytes and their deployment to inflammatory sites."
},
{
"docid": "12205576",
"text": "OBJECTIVE The aim was to describe the sex and socioeconomic differences in patterns of physical activity at work and in leisure time of men and women aged 36 years, and to investigate factors in childhood and adolescence which predict high rates of participation in sports and recreational activities in later life. DESIGN Data collected in childhood, adolescence, and at 36 years on members of a national prospective birth cohort study were used. SETTING The population sample was resident in England, Scotland, and Wales. SUBJECTS A stratified sample of about 3500 men and women was studied regularly from birth until 43 years. MEASUREMENTS AND MAIN RESULTS More men than women reported high rates of sports and recreational activities, gardening, and do-it-yourself. In contrast women reported higher rates of bicycling and walking. Higher levels of education were associated with frequent participation in sports. Individuals often engaged in one type of activity without necessarily engaging in other types. Those who were most active in sport had been above average at sports in school, more outgoing socially in adolescence, had fewer health problems in childhood, were better educated, and had more mothers with a secondary education than those who were less active. CONCLUSIONS Studies that examine the relationship between physical activity and chronic disease should consider a broad range of pursuits rather than extrapolating from only one area of physical activity, and in their explanations should take account of the possible role of childhood characteristics. The findings suggest the importance of developing skills and habits in childhood as well as of encouraging healthier exercise habits in adults who may have had few opportunities or low motivation previously.",
"title": "Physical activity at 36 years: patterns and childhood predictors in a longitudinal study."
},
{
"docid": "9629682",
"text": "The field of macro-imaging has grown considerably with the appearance of innovative clearing methods and confocal microscopes with lasers capable of penetrating increasing tissue depths. The ability to visualize and model the growth of whole organs as they develop from birth, or with manipulation, disease or injury, provides new ways of thinking about development, tissue-wide signaling, and cell-to-cell interactions. The zebrafish (Danio rerio) has ascended from a predominantly developmental model to a leading adult model of tissue regeneration. The unmatched neurogenic and regenerative capacity of the mature central nervous system, in particular, has received much attention, however tools to interrogate the adult brain are sparse. At present there exists no straightforward methods of visualizing changes in the whole adult brain in 3-dimensions (3-D) to examine systemic patterns of cell proliferation or cell populations of interest under physiological, injury, or diseased conditions. The method presented here is the first of its kind to offer an efficient step-by-step pipeline from intraperitoneal injections of the proliferative marker, 5-ethynyl-2'-deoxyuridine (EdU), to whole brain labeling, to a final embedded and cleared brain sample suitable for 3-D imaging using optical projection tomography (OPT). Moreover, this method allows potential for imaging GFP-reporter lines and cell-specific antibodies in the presence or absence of EdU. The small size of the adult zebrafish brain, the highly consistent degree of EdU labeling, and the use of basic clearing agents, benzyl benzoate, and benzyl alcohol, makes this method highly tractable for most laboratories interested in understanding the vertebrate central nervous system in health and disease. Post-processing of OPT-imaged adult zebrafish brains injected with EdU illustrate that proliferative patterns in EdU can readily be observed and analyzed using IMARIS and/or FIJI/IMAGEJ software. This protocol will be a valuable tool to unlock new ways of understanding systemic patterns in cell proliferation in the healthy and injured brain, brain-wide cellular interactions, stem cell niche development, and changes in brain morphology.",
"title": "A Whole Brain Staining, Embedding, and Clearing Pipeline for Adult Zebrafish to Visualize Cell Proliferation and Morphology in 3-Dimensions"
},
{
"docid": "22815457",
"text": "OBJECTIVE To compare the outcome of pregnancy in cohorts of women with singleton pregnancy and history of preterm birth and sonographic short cervix managed with different treatment protocols, namely cerclage, vaginal progesterone or cervical pessary. METHODS This was a comparison of three management protocols for women with singleton pregnancy and a high risk of preterm birth because of a prior spontaneous preterm birth before 34 weeks and a shortened cervical length detected by transvaginal ultrasound. The study included 142 women who were initially treated with cerclage (USA), 59 with vaginal progesterone (UK) and 42 with cervical pessary (Spain). Perinatal outcomes were compared between the three cohorts. RESULTS There were no statistically significant differences in perinatal losses, neonatal morbidity and preterm births among the three groups, apart from a higher rate of preterm birth before 34 weeks' gestation after treatment with vaginal progesterone in comparison with treatment with cervical pessary (32% vs 12%; relative risk (RR) = 2.70; 95% CI, 1.10-6.67). When only the subgroups of women with cervical length < 25 mm, irrespective of gestational age, were compared, the difference between these two cohorts was not statistically significant (RR = 2.21; 95% CI, 0.83-5.89). CONCLUSION Cerclage, vaginal progesterone and pessary appear to have similar effectiveness as management strategies in women with singleton pregnancy, previous spontaneous preterm birth and short cervix. Direct randomized comparisons of these strategies, or combinations thereof, are needed to determine optimal management.",
"title": "Vaginal progesterone, cerclage or cervical pessary for preventing preterm birth in asymptomatic singleton pregnant women with a history of preterm birth and a sonographic short cervix."
},
{
"docid": "5511240",
"text": "Kupffer cells, the phagocytes of fetal origin that line the liver sinusoids, are key contributors of host defense against enteroinvasive bacteria. Here, we found that infection by Listeria monocytogenes induced the early necroptotic death of Kupffer cells, which was followed by monocyte recruitment and an anti-bacterial type 1 inflammatory response. Kupffer cell death also triggered a type 2 response that involved the hepatocyte-derived alarmin interleukin-33 (IL-33) and basophil-derived interleukin-4 (IL-4). This led to the alternative activation of the monocyte-derived macrophages recruited to the liver, which thereby replaced ablated Kupffer cells and restored liver homeostasis. Kupffer cell death is therefore a key signal orchestrating type 1 microbicidal inflammation and type-2-mediated liver repair upon infection. This indicates that beyond the classical dichotomy of type 1 and type 2 responses, these responses can develop sequentially in the context of a bacterial infection and act interdependently, orchestrating liver immune responses and return to homeostasis, respectively.",
"title": "Liver-resident macrophage necroptosis orchestrates type 1 microbicidal inflammation and type-2-mediated tissue repair during bacterial infection."
},
{
"docid": "27567994",
"text": "The generation of tumor-directed cytotoxic T lymphocytes is considered crucial for the induction of antitumor immunity. To activate these CD8(+) T cells, antigen-presenting cells (APCs) must initially acquire tumor cell-associated antigens. The major source of tumor antigens is dead tumor cells, but little is known about how APCs in draining lymph nodes acquire and crosspresent these antigens. Here we show that CD169(+) macrophages phagocytose dead tumor cells transported via lymphatic flow and subsequently crosspresent tumor antigens to CD8(+) T cells. Subcutaneous immunization with irradiated tumor cells protects mice from syngenic tumor. However, tumor antigen-specific CD8(+) T cell activation and subsequent antitumor immunity are severely impaired in mice depleted with CD169(+) macrophages. Neither migratory dendritic cells (DCs) nor lymph node-resident conventional DCs are essential for the crosspresentation of tumor antigens. Thus, we have identified CD169(+) macrophages as lymph node-resident APCs dominating early activation of tumor antigen-specific CD8(+) T cells.",
"title": "CD169-positive macrophages dominate antitumor immunity by crosspresenting dead cell-associated antigens."
},
{
"docid": "5487448",
"text": "Birth weight is a significant predictor of breast cancer risk in adult life and mammary gland mass could be an intermediate stage in this long process. We have studied the association of birth size measurements with mammographic density, a marker of mammary gland mass. For a population-based sample of 893 postmenopausal women without previous cancer in Sweden, we retrieved information on birth size from birth records and their most recent mammography. Film mammograms of the medio-lateral oblique view were digitized and the Cumulus software was used for computer-assisted semi-automated thresholding of mammographic density. Results were analyzed using generalized linear models controlling for possible confounders. Mean percent mammographic density increased when comparing the extreme categories of birth weight (from 15.6% to 18.6%) and head circumference (from 15.5% to 20.4%), and the corresponding linear trends were statistically significant (p values 0.02 and 0.007, respectively). The associations were particularly strong when the cutoff for high versus low mammographic density was set at the relatively high value of 50%. Compared to women weighing 3001-3500 grams at birth, women with birth weights >4000g were at almost 3-fold risk of developing high mammographic density (odds ratio: 2.9, 95% confidence interval 1.1 to 7.9). No association with mammographic density was evident with respect to birth length which, however, is known to be less accurately measured. These results indicate that adult breast density, a powerful predictor of breast cancer risk, has intrauterine roots, as reflected in birth size.",
"title": "Birth weight and mammographic density among postmenopausal women in Sweden."
},
{
"docid": "2605032",
"text": "We investigated if whether intrauterine protein restriction in combination with overfeeding during lactation would cause adult-onset obesity and metabolic disorders. After birth, litters from dams fed with control (17% protein) and low protein (6% protein) diets were adjusted to a size of four (CO and LO groups, respectively) or eight (CC and LC groups, respectively) pups. All of the offspring were fed a diet containing 12% protein from the time of weaning until they were 90 d old. Compared to the CC and LC groups, the CO and LO groups had higher relative and absolute food intakes, oxygen consumption and carbon dioxide production; lower brown adipose tissue weight and lipid content and greater weight gain and absolute and relative white adipose tissue weight and absolute lipid content. Compared with the CO and CC rats, the LC and LO rats exhibited higher relative food intake, brown adipose tissue weight and lipid content, reduced oxygen consumption, carbon dioxide production and spontaneous activity, increased relative retroperitoneal adipose tissue weight and unaltered absolute white adipose tissue weight and lipid content. The fasting serum glucose was similar among the groups. The area under the glucose curve was higher in the LO and CO rats than in the LC and CC rats. The basal insulinemia and homeostasis model assessment of insulin resistance (HOMA-IR) were lower in the LO group than in the other groups. The total area under the insulin curve for the LO rats was similar to the CC rats, and both were lower than the CO and LC rats. Kitt was higher in the LO, LC and CO groups than in the CC group. Thus, intrauterine protein restriction followed by overfeeding during lactation did not induce obesity, but produced glucose intolerance by impairing pancreatic function in adulthood.",
"title": "Intrauterine protein restriction combined with early postnatal overfeeding was not associated with adult-onset obesity but produced glucose intolerance by pancreatic dysfunction"
},
{
"docid": "12411274",
"text": "Skeletal muscle in vertebrates is derived from somites, epithelial structures of the paraxial mesoderm, yet many unrelated reports describe the occasional appearance of myogenic cells from tissues of nonsomite origin, suggesting either transdifferentiation or the persistence of a multipotent progenitor. Here, we show that clonable skeletal myogenic cells are present in the embryonic dorsal aorta of mouse embryos. This finding is based on a detailed clonal analysis of different tissue anlagen at various developmental stages. In vitro, these myogenic cells show the same morphology as satellite cells derived from adult skeletal muscle, and express a number of myogenic and endothelial markers. Surprisingly, the latter are also expressed by adult satellite cells. Furthermore, it is possible to clone myogenic cells from limbs of mutant c-Met-/- embryos, which lack appendicular muscles, but have a normal vascular system. Upon transplantation, aorta-derived myogenic cells participate in postnatal muscle growth and regeneration, and fuse with resident satellite cells. The potential of the vascular system to generate skeletal muscle cells may explain observations of nonsomite skeletal myogenesis and raises the possibility that a subset of satellite cells may derive from the vascular system.",
"title": "Skeletal Myogenic Progenitors Originating from Embryonic Dorsal Aorta Coexpress Endothelial and Myogenic Markers and Contribute to Postnatal Muscle Growth and Regeneration"
},
{
"docid": "30468386",
"text": "The olfactory epithelium houses chemosensory neurons, which transmit odor information from the nose to the brain. In adult mammals, the olfactory epithelium is a uniquely robust neuroproliferative zone, with the ability to replenish its neuronal and non-neuronal populations due to the presence of germinal basal cells. The stem and progenitor cells of these germinal layers, and their regulatory mechanisms, remain incompletely defined. Here we show that progenitor cells expressing c-Kit, a receptor tyrosine kinase marking stem cells in a variety of embryonic tissues, are required for maintenance of the adult neuroepithelium. Mouse genetic fate-mapping analyses show that embryonically, a c-Kit(+) population contributes to olfactory neurogenesis. In adults under conditions of normal turnover, there is relatively sparse c-Kit(+) progenitor cell (ckPC) activity. However, after experimentally induced neuroepithelial injury, ckPCs are activated such that they reconstitute the neuronal population. There are also occasional non-neuronal cells found to arise from ckPCs. Moreover, the selective depletion of the ckPC population, utilizing temporally controlled targeted diphtheria toxin A expression, results in failure of neurogenesis after experimental injury. Analysis of this model indicates that most ckPCs reside among the globose basal cell populations and act downstream of horizontal basal cells, which can serve as stem cells. Identification of the requirement for olfactory c-Kit-expressing progenitors in olfactory maintenance provides new insight into the mechanisms involved in adult olfactory neurogenesis. Additionally, we define an important and previously unrecognized site of adult c-Kit activity.",
"title": "Adult c-Kit(+) progenitor cells are necessary for maintenance and regeneration of olfactory neurons."
},
{
"docid": "15274349",
"text": "Almost immediately after a human being is born, so too is a new microbial ecosystem, one that resides in that person's gastrointestinal tract. Although it is a universal and integral part of human biology, the temporal progression of this process, the sources of the microbes that make up the ecosystem, how and why it varies from one infant to another, and how the composition of this ecosystem influences human physiology, development, and disease are still poorly understood. As a step toward systematically investigating these questions, we designed a microarray to detect and quantitate the small subunit ribosomal RNA (SSU rRNA) gene sequences of most currently recognized species and taxonomic groups of bacteria. We used this microarray, along with sequencing of cloned libraries of PCR-amplified SSU rDNA, to profile the microbial communities in an average of 26 stool samples each from 14 healthy, full-term human infants, including a pair of dizygotic twins, beginning with the first stool after birth and continuing at defined intervals throughout the first year of life. To investigate possible origins of the infant microbiota, we also profiled vaginal and milk samples from most of the mothers, and stool samples from all of the mothers, most of the fathers, and two siblings. The composition and temporal patterns of the microbial communities varied widely from baby to baby. Despite considerable temporal variation, the distinct features of each baby's microbial community were recognizable for intervals of weeks to months. The strikingly parallel temporal patterns of the twins suggested that incidental environmental exposures play a major role in determining the distinctive characteristics of the microbial community in each baby. By the end of the first year of life, the idiosyncratic microbial ecosystems in each baby, although still distinct, had converged toward a profile characteristic of the adult gastrointestinal tract.",
"title": "Development of the Human Infant Intestinal Microbiota"
},
{
"docid": "36618603",
"text": "The differentiation in vitro of murine embryonic stem cells to embryoid bodies mimics events that occur in vivo shortly before and after embryonic implantation. We have used this system, together with differential cDNA cloning, to identify genes the expression of which is regulated during early embryogenesis. Here we describe the isolation of several such cDNA clones, one of which corresponds to the gene H19. This gene is activated in extraembryonic cell types at the time of implantation, suggesting that it may play a role at this stage of development, and is subsequently expressed in all of the cells of the mid-gestation embryo with the striking exception of most of those of the developing central and peripheral nervous systems. After birth, expression of this gene ceases or is dramatically reduced in all tissues.",
"title": "The murine H19 gene is activated during embryonic stem cell differentiation in vitro and at the time of implantation in the developing embryo."
},
{
"docid": "37480103",
"text": "CONTEXT During pregnancy, serum levels of estrogen, progesterone, and other hormones are markedly higher than during other periods of life. Pregnancy hormones primarily are produced in the placenta, and signs of placental impairment may serve as indirect markers of hormone exposures during pregnancy. During pregnancy, these markers have been inconsistently associated with subsequent risk of breast cancer in the mother. OBJECTIVE To examine associations between indirect markers of hormonal exposures, such as placental weight and other pregnancy characteristics, and maternal risk of developing breast cancer. DESIGN AND SETTING Population-based cohort study using data from the Swedish Birth Register, the Swedish Cancer Register, the Swedish Cause of Death Register, and the Swedish Register of Population and Population Changes. PARTICIPANTS Women included in the Sweden Birth Register who delivered singletons between 1982 and 1989, with complete information on date of birth and gestational age. Women were followed up until the occurrence of breast cancer, death, or end of follow-up (December 31, 2001). Cox proportional hazards models were used to estimate associations between hormone exposures and risks of breast cancer. MAIN OUTCOME MEASURE Incidence of invasive breast cancer. RESULTS Of 314,019 women in the cohort, 2216 (0.7%) developed breast cancer during the follow-up through 2001, of whom 2100 (95%) were diagnosed before age 50 years. Compared with women who had placentas weighing less than 500 g in 2 consecutive pregnancies, the risk of breast cancer was increased among women whose placentas weighed between 500 and 699 g in their first pregnancy and at least 700 g in their second pregnancy (or vice versa) (adjusted hazard ratio, 1.82; 95% confidence interval [CI], 1.07-3.08), and the corresponding risk was doubled among women whose placentas weighed at least 700 g in both pregnancies (adjusted hazard ratio, 2.05; 95% CI, 1.15-3.64). A high birth weight (> or =4000 g) in 2 successive births was associated with an increased risk of breast cancer before but not after adjusting for placental weight and other covariates (adjusted hazard ratio, 1.10; 95% CI, 0.76-1.59). CONCLUSIONS Placental weight is positively associated with maternal risk of breast cancer. These results further support the hypothesis that pregnancy hormones are important modifiers of subsequent maternal breast cancer risk.",
"title": "Pregnancy characteristics and maternal risk of breast cancer."
},
{
"docid": "25148216",
"text": "Several members of the Kruppel-like factor (KLF) family of transcription factors play important roles in differentiation, survival, and trafficking of blood and immune cell types. We demonstrate in this study that hematopoietic cells from KLF4(-/-) fetal livers (FL) contained normal numbers of functional hematopoietic progenitor cells, were radioprotective, and performed as well as KLF4(+/+) cells in competitive repopulation assays. However, hematopoietic \"KLF4(-/-) chimeras\" generated by transplantation of KLF4(-/-) fetal livers cells into lethally irradiated wild-type mice completely lacked circulating inflammatory (CD115(+)Gr1(+)) monocytes, and had reduced numbers of resident (CD115(+)Gr1(-)) monocytes. Although the numbers and function of peritoneal macrophages were normal in KLF4(-/-) chimeras, bone marrow monocytic cells from KLF4(-/-) chimeras expressed lower levels of key trafficking molecules and were more apoptotic. Thus, our in vivo loss-of-function studies demonstrate that KLF4, previously shown to mediate proinflammatory signaling in human macrophages in vitro, is essential for differentiation of mouse inflammatory monocytes, and is involved in the differentiation of resident monocytes. In addition, inducible expression of KLF4 in the HL60 human acute myeloid leukemia cell line stimulated monocytic differentiation and enhanced 12-O-tetradecanoylphorbol 13-acetate induced macrophage differentiation, but blocked all-trans-retinoic acid induced granulocytic differentiation of HL60 cells. The inflammation-selective effects of loss-of-KLF4 and the gain-of-KLF4-induced monocytic differentiation in HL60 cells identify KLF4 as a key regulator of monocytic differentiation and a potential target for translational immune modulation.",
"title": "Kruppel-like factor 4 is essential for inflammatory monocyte differentiation in vivo."
},
{
"docid": "16905344",
"text": "Injured axons of the adult CNS undergo lengthy retraction from the initial site of axotomy after spinal cord injury. Macrophage infiltration correlates spatiotemporally with this deleterious phenomenon, but the direct involvement of these inflammatory cells has not been demonstrated. In the present study, we examined the role of macrophages in axonal retraction within the dorsal columns after spinal cord injury in vivo and found that retraction occurred between days 2 and 28 after lesion and that the ends of injured axons were associated with ED-1+ cells. Clodronate liposome-mediated depletion of infiltrating macrophages resulted in a significant reduction in axonal retraction; however, we saw no evidence of regeneration. We used time-lapse imaging of adult dorsal root ganglion neurons in an in vitro model of the glial scar to examine macrophage-axon interactions and observed that adhesive contacts and considerable physical interplay between macrophages and dystrophic axons led to extensive axonal retraction. The induction of retraction was dependent on both the growth state of the axon and the activation state of the macrophage. Only dystrophic adult axons were susceptible to macrophage \"attack. \" Unlike intrinsically active cell line macrophages, both primary macrophages and microglia required activation to induce axonal retraction. Contact with astrocytes had no deleterious effect on adult dystrophic axons, suggesting that the induction of extensive retraction was specific to phagocytic cells. Our data are the first to indicate a direct role of activated macrophages in axonal retraction by physical cell-cell interactions with injured axons.",
"title": "Another Barrier to Regeneration in the CNS: Activated Macrophages Induce Extensive Retraction of Dystrophic Axons through Direct Physical Interactions"
},
{
"docid": "9412420",
"text": "Mesenchymal stem cells (MSCs) commonly defined by in vitro functions have entered clinical application despite little definition of their function in residence. Here, we report genetic pulse-chase experiments that define osteoblastic cells as short-lived and nonreplicative, requiring replenishment from bone-marrow-derived, Mx1(+) stromal cells with \"MSC\" features. These cells respond to tissue stress and migrate to sites of injury, supplying new osteoblasts during fracture healing. Single cell transplantation yielded progeny that both preserve progenitor function and differentiate into osteoblasts, producing new bone. They are capable of local and systemic translocation and serial transplantation. While these cells meet current definitions of MSCs in vitro, they are osteolineage restricted in vivo in growing and adult animals. Therefore, bone-marrow-derived MSCs may be a heterogeneous population with the Mx1(+) population, representing a highly dynamic and stress responsive stem/progenitor cell population of fate-restricted potential that feeds the high cell replacement demands of the adult skeleton.",
"title": "Endogenous bone marrow MSCs are dynamic, fate-restricted participants in bone maintenance and regeneration."
},
{
"docid": "3155731",
"text": "T cells have crucial roles in protection against infection and cancer. Although the trafficking of memory T cells around the body is integral to their capacity to provide immune protection, studies have shown that specialization of some memory T cells into unique tissue-resident subsets gives the host enhanced regional immunity. In recent years, there has been considerable progress in our understanding of tissue-resident T cell development and function, revealing mechanisms for enhanced protective immunity that have the potential to influence rational vaccine design. This Review discusses the major advances and the emerging concepts in this field, summarizes what is known about the differentiation and the protective functions of tissue-resident memory T cells in different tissues in the body and highlights key unanswered questions.",
"title": "Tissue-resident memory T cells: local specialists in immune defence"
},
{
"docid": "36708463",
"text": "A major question is whether genes encoded on the sex chromosomes act directly in non-gonadal tissues to cause sex differences in development or function, or whether all sex differences in somatic tissues are induced by gonadal secretions. As part of this question we asked whether mouse X-Y homologous gene pairs are expressed in brain in a sex-specific fashion. Using RT-PCR and northern blot analysis, we assessed mRNA expression in brain of eight Y-linked genes as well as their X-linked homologues, at three ages: 13.5 days post coitum, the day of birth (P1) and adult. Transcripts of six Y genes were expressed at one or more ages: Usp9y, Ube1y, Smcy, Eif2s3y, Uty and Dby. Their expression also occurred in XY female brain, and therefore does not require testicular secretions. Six X-linked homologues (Usp9x, Ube1x, Smcx, Eif2s3x, Utx and Dbx) were also expressed in brain, and in adulthood all of these transcripts were expressed at significantly higher levels in brains of females than in brains of males, irrespective of their X-inactivation status. For five of these gene pairs, the expression of the Y-linked homologue in males was not sufficient to compensate for the female bias in X gene expression. Three X-Y gene pairs, Usp9x/y, Ube1x/y and Eif2s3x/y, appeared to be differentially regulated (expressed in brain in a different age- or tissue-dependent pattern), and hence may not be functionally equivalent. These sex differences in X-Y gene expression suggest several mechanisms by which these genes may participate in sex differences in brain development and function.",
"title": "Sex differences in sex chromosome gene expression in mouse brain."
},
{
"docid": "8698208",
"text": "Rett syndrome (RTT) is an inherited neurodevelopmental disorder of females that occurs once in 10,000–15,000 births. Affected females develop normally for 6–18 months, but then lose voluntary movements, including speech and hand skills. Most RTT patients are heterozygous for mutations in the X-linked gene MECP2 (refs. 3–12), encoding a protein that binds to methylated sites in genomic DNA and facilitates gene silencing. Previous work with Mecp2-null embryonic stem cells indicated that MeCP2 is essential for mouse embryogenesis. Here we generate mice lacking Mecp2 using Cre-loxP technology. Both Mecp2-null mice and mice in which Mecp2 was deleted in brain showed severe neurological symptoms at approximately six weeks of age. Compensation for absence of MeCP2 in other tissues by MeCP1 (refs. 19,20) was not apparent in genetic or biochemical tests. After several months, heterozygous female mice also showed behavioral symptoms. The overlapping delay before symptom onset in humans and mice, despite their profoundly different rates of development, raises the possibility that stability of brain function, not brain development per se, is compromised by the absence of MeCP2.",
"title": "A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome"
},
{
"docid": "16322674",
"text": "BACKGROUND Birth size, perhaps a proxy for prenatal environment, might be a correlate of subsequent breast cancer risk, but findings from epidemiological studies have been inconsistent. We re-analysed individual participant data from published and unpublished studies to obtain more precise estimates of the magnitude and shape of the birth size-breast cancer association. METHODS AND FINDINGS Studies were identified through computer-assisted and manual searches, and personal communication with investigators. Individual participant data from 32 studies, comprising 22,058 breast cancer cases, were obtained. Random effect models were used, if appropriate, to combine study-specific estimates of effect. Birth weight was positively associated with breast cancer risk in studies based on birth records (pooled relative risk [RR] per one standard deviation [SD] [= 0.5 kg] increment in birth weight: 1.06; 95% confidence interval [CI] 1.02-1.09) and parental recall when the participants were children (1.02; 95% CI 0.99-1.05), but not in those based on adult self-reports, or maternal recall during the woman's adulthood (0.98; 95% CI 0.95-1.01) (p for heterogeneity between data sources = 0.003). Relative to women who weighed 3.000-3.499 kg, the risk was 0.96 (CI 0.80-1.16) in those who weighed < 2.500 kg, and 1.12 (95% CI 1.00-1.25) in those who weighed > or = 4.000 kg (p for linear trend = 0.001) in birth record data. Birth length and head circumference from birth records were also positively associated with breast cancer risk (pooled RR per one SD increment: 1.06 [95% CI 1.03-1.10] and 1.09 [95% CI 1.03-1.15], respectively). Simultaneous adjustment for these three birth size variables showed that length was the strongest independent predictor of risk. The birth size effects did not appear to be confounded or mediated by established breast cancer risk factors and were not modified by age or menopausal status. The cumulative incidence of breast cancer per 100 women by age 80 y in the study populations was estimated to be 10.0, 10.0, 10.4, and 11.5 in those who were, respectively, in the bottom, second, third, and top fourths of the birth length distribution. CONCLUSIONS This pooled analysis of individual participant data is consistent with birth size, and in particular birth length, being an independent correlate of breast cancer risk in adulthood.",
"title": "Birth Size and Breast Cancer Risk: Re-analysis of Individual Participant Data from 32 Studies"
},
{
"docid": "21489324",
"text": "Located in the Kassena-Nankana districts of northern Ghana, the Navrongo health and demographic surveillance system (NHDSS) was established in 1992 by the Navrongo health research centre (NHRC). The NHRC is one of three research centres of the Ghana health service. The activities and potential of the NHDSS for collaborative research are described. The NHDSS monitors health and demographic dynamics of the two Kassena-Nankana districts of northern Ghana and facilitates evaluation of the morbidity and mortality impact of health and social interventions. The total population currently under surveillance is 152 000 residing in 32 000 households. Events monitored routinely include pregnancies, births, morbidity, deaths, migration, marriages and vaccination coverage. Data updates are done every 4 months by trained fieldworkers. The NHRC also undertakes biomedical and socio-economic studies. Additional features of the NHDSS include the community key informant system where trained volunteers routinely report key events, such as births and deaths as they occur in their locality and the verbal autopsy (VA) system for determining the probable causes of deaths that occur at the community level. Data from the NHDSS are shared with funders and collaborators and partners in the INDEPTH Network. The Director of the NHDSS is the contact person for potential collaboration with the NHDSS and the use of its data.",
"title": "Profile of the Navrongo Health and Demographic Surveillance System."
},
{
"docid": "19489351",
"text": "Somatic stem cells have been identified in multiple adult tissues. Whether self-renewal occurs symmetrically or asymmetrically is key to understanding long-term stem cell maintenance and generation of progeny for cell replacement. In the adult mouse brain, neural stem cells (NSCs) (B1 cells) are retained in the walls of the lateral ventricles (ventricular-subventricular zone [V-SVZ]). The mechanism of B1 cell retention into adulthood for lifelong neurogenesis is unknown. Using multiple clonal labeling techniques, we show that the vast majority of B1 cells divide symmetrically. Whereas 20%-30% symmetrically self-renew and can remain in the niche for several months before generating neurons, 70%-80% undergo consuming divisions generating progeny, resulting in the depletion of B1 cells over time. This cellular mechanism decouples self-renewal from the generation of progeny. Limited rounds of symmetric self-renewal and consuming symmetric differentiation divisions can explain the levels of neurogenesis observed throughout life.",
"title": "Adult Neurogenesis Is Sustained by Symmetric Self-Renewal and Differentiation."
}
] |
7157
|
Can a put option and call option be exercised for the same stock with different strike prices?
|
[
{
"docid": "89484",
"text": "You could have both options exercised (and assigned to you) on the same day, but I don't think you could lose money on both on the same day. The reason is that while exercises are immediate, assignments are processed after the markets close at the end of each day. See http://www.888options.com/help/faq/assignment.jsp for details. So you would get both assignments at the same time, that night. The net effect should be that you don't own any stock (someone would put you the stock, then it'd be called away) and you don't have the options anymore. You should have incoming cash of $1500 selling the stock to the call exerciser and outgoing cash of $1300 buying from the put exerciser, right? So you would have no more options but $200 more cash in your account in the morning. You bought at 13 and sold at 15. This options position is an agreement to buy at 13 and sell at 15 at someone else's option. The way you lose money is if one of the options isn't exercised while the other is, i.e. if the stock is below 13 so nobody is going to opt to buy from you at 15, but they'll sell to you at 13; or above 15 so nobody is going to opt to sell to you at 13, but they'll buy from you at 15. You make money if neither is exercised (you keep the premium you sold for) or both are exercised (you keep the gap between the two, plus the premium). Having both exercised is surely rare, since early exercise is rare to begin with, and tends to happen when options are deep in the money; so you'd expect both to be exercised if both are deep in the money at some point. Having both be exercised on the same day ... can't be common, but it's maybe most likely just before expiration with minimal time value, if the stock moves around quickly so both options are in the money at some point during the day.",
"title": ""
},
{
"docid": "37152",
"text": "\"What you did is called a \"\"strangle.\"\" It's rather unlikely that both will be exercised on the same day. But yes, it can happen. That is if the market is very volatile on a given day, so that the stock hits 13 in the morning, the put gets exercised, and then hits 15 later in the day, so the call gets exercised. Or vice versa. More to the point, the prices are close enough that one might be hit on one day, and the other on a DIFFERENT day. In either case, if one side gets hit, you need to reevaluate your position in the other. But basically, any open position you have can be hit at any time. The only way to avoid this risk is not to have positions.\"",
"title": ""
}
] |
[
{
"docid": "278373",
"text": "\"According to the book of Hull, american and european calls on non-dividend paying stocks should have the same value. American puts, however, should be equals to, or more valuable than, european puts. The reason for this is the time value of money. In a put, you get the option to sell a stock at a given strike price. If you exercise this option at t=0, you receive the strike price at t=0 and can invest it at the risk-free rate. Lets imagine the rf rate is 10% and the strike price is 10$. this means at t=1, you would get 11.0517$. If, on the other hand, you did'nt exercise the option early, at t=1 you would simply receive the strike price (10$). Basically, the strike price, which is your payoff for a put option, doesn't earn interest. Another way to look at this is that an option is composed of two elements: The \"\"insurance\"\" element and the time value of the option. The insurance element is what you pay in order to have the option to buy a stock at a certain price. For put options, it is equals to the payout= max(K-S, 0) where K=Strike Price and St= Stock price. The time value of the option can be thought of as a risk-premium. It's difference between the value of the option and the insurance element. If the benefits of exercising a put option early (i.e- earning the risk free rate on the proceeds) outweighs the time value of the put option, it should be exercised early. Yet another way to look at this is by looking at the upper bounds of put options. For a european put, today's value of the option can never be worth more than the present value of the strike price discounted at the risk-free rate. If this rule isn't respected, there would be an arbitrage opportunity by simply investing at the risk-free rate. For an american put, since it can be exercised at any time, the maximum value it can take today is simply equals to the strike price. Therefore, since the PV of the strike price is smaller than the strike price, the american put can have a bigger value. Bear in mind this is for a non-dividend paying stock. As previously mentioned, if a stock pays a dividend it might also be optimal to exercise just before these are paid.\"",
"title": ""
},
{
"docid": "193303",
"text": "The value of an option has 2 components, the extrinsic or time value element and the intrinsic value from the difference in the strike price and the underlying asset price. With either an American or European option the intrinsic value of a call option can be 'locked in' any time by selling the same amount of the underlying asset (whether that be a stock, a future etc). Further, the time value of any option can be monitised by delta hedging the option, i.e. buying or selling an amount of the underlying asset weighted by the measure of certainty (delta) of the option being in the money at expiry. Instead, the extra value of the American option comes from the financial benefit of being able to realise the value of the underlying asset early. For a dividend paying stock this will predominantly be the dividend. But for non-dividend paying stocks or futures, the buyer of an in-the-money option can realise their intrinsic gains on the option early and earn interest on the profits today. But what they sacrifice is the timevalue of the option. However when an option becomes very in the money and the delta approaches 1 or -1, the discounting of the intrinsic value (i.e. the extra amount a future cash flow is worth each day as we draw closer to payment) becomes larger than the 'theta' or time value decay of the option. Then it becomes optimal to early exercise, abandon the optionality and realise the monetary gains upfront. For a non-dividend paying stock, the value of the American call option is actually the same as the European. The spot price of the stock will be lower than the forward price at expiry discounted by the risk free rate (or your cost of funding). This will exactly offset the monetary gain by exercising early and banking the proceeds. However for an option on a future, the value today of the underlying asset (the future) is the same as at expiry and its possible to fully realise the interest earned on the money received today. Hence the American call option is worth more. For both examples the American put option is worth more, slightly more so for the stock. As the stock's spot price is lower than the forward price, the owner of the put option realises a higher (undiscounted) intrinsic profit from selling the stock at the higher strike price today than waiting till expiry, as well as realising the interest earned. Liquidity may influence the perceived value of being able to exercise early but its not a tangible factor that is added to the commonly used maths of the option valuation, and isn't really a consideration for most of the assets that have tradeable option markets. It's also important to remember at any point in the life of the option, you don't know the future price path. You're only modelling the distribution of probable outcomes. What subsequently happens after you early exercise an American option no longer has any bearing on its value; this is now zero! Whether the stock subsequently crashes in price is irrelevent. What is relevant is that when you early exercise a call you 'give up' all potential upside protected by the limit to your downside from the strike price.",
"title": ""
},
{
"docid": "195152",
"text": "Put options are contracts to sell. You pay me a fee for the right to put the stock (or other underlying security) in my hands if you want to. That happens on a specific date (the strike date) and a specified price (the strike price). You can decide not to exercise that right, but I must follow through and let you sell it to me if you want to. Put options can be used by the purchaser to cap losses. For example: You purchase a PUT option for GE Oct19 13.00 from me. On October 19th, you can make me let you sell your GE stock to me for $13.00 a share. If the price for GE has fallen to $12.00, that would be a good idea. If its now at $15.00 a share, you will probably keep the GE or sell it at the current market price. Call options are contracts to buy. The same idea only in the other direction: You pay me a fee for the right to call the stock away from me. Calls also have a strike date and strike price. Like a put, you can choose not to exercises it. You can choose to buy the stock from me (on the strike date for the strike price), but I have to let you buy it from me if you want to. For example: You purchase a CALL option for GE Oct19 16.00 option from me. On October 19th, you can buy my GE stock from me for $16.00 a share. If the current price is $17.50, you should make me let you buy if from me for $16.00. If its less than $16.00, you could by it at the current market price for less. Commonly, options are for a block of 100 shares of the underlying security. Note: this is a general description. Options can be very complicated. The fee you pay for the option and the transaction fees associated with the shares affects whether or not exercising is financially beneficial. Options can be VERY RISKY. You can loose all your money as there is no innate value in the option, only how it relates to the underlying security. Before your brokerage will let you trade, there are disclosures you must read and affirm that you understand the risk.",
"title": ""
},
{
"docid": "119976",
"text": "\"One alternative strategy you may want to consider is writing covered calls on the stock you have \"\"just sitting there\"\". This will allow you to earn a return (the premium from the calls) without necessarily having to give up your holding. As a brief overview, \"\"options\"\" are derivatives that give the holder the right (or option) to buy or sell shares at a specified price. Holders of call options with a strike prike $x on a particular security have the right to purchase that security at the strike price $x. Conversely, holders of put options with a strike price of $x have the right to sell that security at the strike price $x. Always on the other side of a call or put option is a person that has sold the option, which is called \"\"writing\"\" the option. If this person writes a call option, then he will be obligated to sell a certain amount of stock (100 shares per contract) at the strike price if that option is exercised. A writer of a put option will be obligated to by 100 shares per contract at the strike price if that option is exercised. Covered calls involve writing call contracts on stock that you own. For example, say you own 100 shares of AAPL, and that AAPL is currently trading for $330. You decide to write a Jan 21, 2012 call on these shares at a strike price of $340, earning you a premium of say $300. Two things can now happen: if the price of AAPL is not at least $340 on January 21, then the options are \"\"out of the money\"\" and will expire unexercised (why exercise an option to buy at $340 when you can buy at the currently cheaper market price?). You keep your AAPL stock plus the $300 premium you earn. If, however, the price of AAPL is greater than $340, the option will be exercised and you will now be required to sell the shares you own at $340. You will earn a return of $10/share ($340-$330), plus the $300 premium from the call option. You still make out in the end, but have unfortunately incurred an opportunity cost, as had you not written the call option you would have been able to sell at the market price, which is higher than the $340 strike price. Covered calls are considered relatively safe and conservative, however the strategy is most effective for stocks that are expected to stay within a relatively narrow price range for the duration of the contract. They do provide one option of earning additional money on stocks you are currently holding, albeit at the risk of giving up some returns if the stock price rises above the strike price.\"",
"title": ""
},
{
"docid": "362473",
"text": "\"Seems like you are concerned with something called assignment risk. It's an inherent risk of selling options: you are giving somebody the right, but not the obligation, to sell to you 100 shares of GOOGL. Option buyers pay a premium to have that right - the extrinsic value. When they exercise the option, the option immediately disappears. Together with it, all the extrinsic value disappears. So, the lower the extrinsic value, the higher the assignment risk. Usually, option contracts that are very close to expiration (let's say, around 2 to 3 weeks to expiration or less) have significantly lower extrinsic value than longer option contracts. Also, generally speaking, the deeper ITM an option contract is, the lower extrinsic value it will have. So, to reduce assignment risk, I usually close out my option positions 1-2 weeks before expiration, especially the contracts that are deep in the money. edit: to make sure this is clear, based on a comment I've just seen on your question. To \"\"close out an options position\"\", you just have to create the \"\"opposite\"\" trade. So, if you sell a Put, you close that by buying back that exact same put. Just like stock: if you buy stock, you have a position; you close that position by selling the exact same stock, in the exact same amount. That's a very common thing to do with options. A post in Tradeking's forums, very old post, but with an interesting piece of data from the OCC, states that 35% of the options expire worthless, and 48% are bought or sold before expiration to close the position - only 17% of the contracts are actually exercised! (http://community.tradeking.com/members/optionsguy/blogs/11260-what-percentage-of-options-get-exercised) A few other things to keep in mind: certain stocks have \"\"mini options contracts\"\", that would correspond to a lot of 10 shares of stock. These contracts are usually not very liquid, though, so you might not get great prices when opening/closing positions you said in a comment, \"\"I cannot use this strategy to buy stocks like GOOGL\"\"; if the reason is because 100*GOOGL is too much to fit in your buying power, that's a pretty big risk - the assignment could result in a margin call! if margin call is not really your concern, but your concern is more like the risk of holding 100 shares of GOOGL, you can help manage that by buying some lower strike Puts (that have smaller absolute delta than your Put), or selling some calls against your short put. Both strategies, while very different, will effectively reduce your delta exposure. You'd get 100 deltas from the 100 shares of GOOGL, but you'd get some negative deltas by holding the lower strike Put, or by writing the higher strike Call. So as the stock moves around, your account value would move less than the exposure equivalent to 100 shares of stock.\"",
"title": ""
},
{
"docid": "194605",
"text": "There are a few situations in which it may be advantageous to exercise early. Wikipedia actually has a good explanation: Option Style, Difference in value To account for the American's higher value there must be some situations in which it is optimal to exercise the American option before the expiration date. This can arise in several ways, such as: An in the money (ITM) call option on a stock is often exercised just before the stock pays a dividend that would lower its value by more than the option's remaining time value. A put option will usually be exercised early if the underlying asset files for bankruptcy.[3] A deep ITM currency option (FX option) where the strike currency has a lower interest rate than the currency to be received will often be exercised early because the time value sacrificed is less valuable than the expected depreciation of the received currency against the strike. An American bond option on the dirty price of a bond (such as some convertible bonds) may be exercised immediately if ITM and a coupon is due. A put option on gold will be exercised early when deep ITM, because gold tends to hold its value whereas the currency used as the strike is often expected to lose value through inflation if the holder waits until final maturity to exercise the option (they will almost certainly exercise a contract deep ITM, minimizing its time value).[citation needed]",
"title": ""
},
{
"docid": "207253",
"text": "According to this article: With an all-stock merger, the number of shares covered by a call option is changed to adjust for the value of the buyout. The options on the bought-out company will change to options on the buyer stock at the same strike price, but for a different number of shares. Normally, one option is for 100 shares of the underlying stock. For example, company A buys company B, exchanging 1/2 share of A for each share of B. Options purchased on company B stock would change to options on company A, with 50 shares of stock delivered if the option is exercised. This outcome strongly suggests that, in general, holders of options should cash out once the takeover is announced, before the transactions takes place. Since the acquiring company will typically offer a significant premium, this will offer an opportunity for instant profits for call option holders while at the same time being a big negative for put option holders. However, it is possible in some cases where the nominal price of the two companies favours the SML company (ie. the share prices of SML is lower than that of BIG), the holder of a call option may wish to hold onto their options. (And, possibly, conversely for put option holders.)",
"title": ""
},
{
"docid": "576364",
"text": "\"You're forgetting the fundamental issue, that you never have to actually exercise the options you buy. You can either sell them to someone else or, if they're out of the money, let them expire and take the loss. It isn't uncommon at all for people to buy both a put and call option (this is a \"\"straddle\"\" when the strike price of both the put and call are the same). From Investopedia.com: A straddle is an options strategy in which the investor holds a position in both a call and put with the same strike price and expiration date, paying both premiums. This strategy allows the investor to make a profit regardless of whether the price of the security goes up or down, assuming the stock price changes somewhat significantly. Read more: Straddle http://www.investopedia.com/terms/s/straddle.asp#ixzz4ZYytV0pT\"",
"title": ""
},
{
"docid": "502164",
"text": "I am very surprised no one mentioned the Stock Repair Option Strategy which has real benefits and is one of the mainstream Option Strategies. Quote: Who Should Consider Using the Stock Repair Strategy? In a nutshell, you are buying call options with current strike price (at-the-money) and sell call options with higher strike price (out-of-the-money), all with the same expiry dates. The only reason to also sell call options here is to recover your premium paid for the other call options. If you are comfortable paying that premium, you just buy the call options without selling the others. In case your stock will rise moderately to a price between the two strike prices, your call option will rise together with your stock, so you will be faster to recover your money. This is the main reason it is called Repair. If you have sold any call options, as the price rises, you have to be careful when it reaches the strike price of the options sold, as from there on you will begin incurring losses. It is however exactly the lucky outcome you were hoping for, your stock is higher, and you can buy back those loss making options - then or shortly before. If you didn't sell any options and payed your premium, you don't need to worry at all at this stage. WARNING It should be noted that the Stock Repair Strategy offers no protection for your stock price further falling down. In that case all those options will expire worthless or you can sell back the ones your bought but likely not for much. In order to have the downside protection for your stock, there are other strategies, the simplest one being buying a Put Option at-the-money or slightly lower. That will effectively cut your possible losses to the Option Premium (which is the main use of that option). Again, if you hate to pay that premium, you can offset it by selling other options that you either hope won't be exercised or take steps to protect you against those.",
"title": ""
},
{
"docid": "525390",
"text": "\"A company has 100,000 shares and 100,000 unexercised call options (company issued). Share price and strike price both at $1. What country is this related to? I ask because, in the US, most people I know associate a \"\"call\"\" option with the instrument that is equivalent to 100 shares. So 100,000 calls would be 10,000,000 shares, which exceeds the number of shares you're saying the company has. I don't know if that means you pulled the numbers out of thin air, or whether it means you're thinking of a different type of option? Perhaps you meant incentive stock options meant to be given to employees? Each one of those is equivalent to a single share. They just aren't called \"\"call options\"\". In the rest of my answer, I'm going to assume you meant stock options. I assume the fact that these options exist will slow any price increases on the underlying shares due to potential dilution? I don't think the company can just create stock options without creating the underlying shares in the first place. Said another way, a more likely scenario is that company creates 200,000 shares and agrees to float 50% of them while reserving the other 50% as the pool for incentive employee stock. They then choose to give the employees options on the stock in the incentive pool, rather than outright grants of the stock, for various reasons. (One of which is being nice to the employees in regards to taxes since there is no US tax due at grant time if the strike price is the current price of the underlying stock.) An alternative scenario when the company shares are liquidly traded is that the company simply plans to buy back shares from the market in order to give employees their shares when options are exercised. In this case, the company needs the cash on hand, or cash flow to take money from, to buy those shares at current prices. Anyway, in either case, there is no dilution happening WHEN the options get exercised. Any dilution happened before or at the time the options were created. Meaning, the total number of shares in the company was already pre-set at an earlier time. As a result, the fact that the options exist in themselves will not slow price changes on the stock. However, price changes will be impacted by the total float of shares in the company, or the impact to cash flow if the company has to buy shares to redeem its option commitments. This is almost the same thing you're asking about, but it is technically different as to timing. If this is the case, can this be factored into any option pricing models like black-scholes? You're including the effect just by considering the total float of shares and net profits from cash flow when doing your modelling.\"",
"title": ""
},
{
"docid": "440458",
"text": "1) Yes, both of your scenarios would lead to earning $10 on the transaction, at the strike date. If you purchased both of them (call it Scenario 3), you would make $20. 2) As to why this transaction may not be possible, consider the following: The Call and Put pricing you describe may not be available. What you have actually created is called 'arbitrage' - 2 identical assets can be bought and sold at different prices, leading to a zero-risk gain for the investor. In the real marketplace, if an option to buy asset X in January cost $90, would an option to sell asset X in January provide $110? Without adding additional complexity about the features of asset x or the features of the options, buying a Call option is the same as selling a Put option [well, when selling a Put option you don't have the ability to choose whether the option is exercised, meaning buying options has value that selling options does not, but ignore that for a moment]. That means that you have arranged a marketplace where you would buy a Call option for only $90, but the seller of that same option would somehow receive $110. For added clarity, consider the following: What if, in your example, the future price ended up being $200? Then, you could exercise your call option, buying a share for $90, selling it for $200, making $110 profit. You would not exercise your put option, making your total profit $110. Now consider: What if, in your example, the future price ended up being $10? You would buy for $10, exercise your put option and sell for $110, making a profit of $100. You would not exercise your call option, making your total profit $100. This highlights that if your initial assumptions existed, you would earn money (at least $20, and at most, unlimited based on a skyrocketing price compared to your $90 put option) regardless of the future price. Therefore such a scenario would not exist in the initial pricing of the options. Now perhaps there is an initial fee involved with the options, where the buyer or seller pays extra money up-front, regardless of the future price. That is a different scenario, and gets into the actual nature of options, where investors will arrange multiple simultaneous transactions in order to limit risk and retain reward within a certain band of future prices. As pointed out by @Nick R, this fee would be very significant, for a call option which had a price set below the current price. Typically, options are sold 'out of the money' initially, which means that at the current share price (at the time the option is purchased), executing the option would lose you money. If you purchase an 'in the money' option, the transaction cost initially would by higher than any apparent gain you might have by immediately executing the option. For a more realistic Options example, assume that it costs $15 initially to buy either the Call option, or the Put option. In that case, after buying both options as listed in your scenarios you would earn a profit if the share price exceeded $120 [The $120 sale price less the $90 call option = $30, which is your total fee initially], or dropped below $80 [The $110 Put price less the $80 purchase price = $30]. This type of transaction implies that you expect the price to either swing up, or swing down, but not fall within the band between $80-$120. Perhaps you might do this if there was an upcoming election or other known event, which might be a failure or success, and you think the market has not properly accounted for either scenario in advance. I will leave further discussion on that topic [arranging options of different prices to create specific bands of profitability / loss] to another answer (or other questions which likely already exist on this site, or in fact, other resources), because it gets more complicated after that point, and is outside the root of your question.",
"title": ""
},
{
"docid": "469382",
"text": "If you are in the money at expiration you are going to get assigned to the person on the other side of the contract. This is an extremely high probability. The only randomness comes from before expiration. Where you may be assigned because a holder exercised the option before expiration, this can unbalance some of your strategies. But in exchange, you get all the premium that was still left on the option when they exercised. An in the money option, at expiration, has no premium. The value of your in the money option is Current Stock price - Strike Price, for a call. And Strike price - Current Stock price, for a put. Thats why there is no free lunch in this scenario.",
"title": ""
},
{
"docid": "457059",
"text": "\"There are different schools of thought. You can ask the IRS - and it would not surprise me if you got different answers on different phone calls. One interpretation is that a put is not \"\"substantially identical\"\" to the disposed stock, therefore no wash is triggered by that sale. However if that put is exercised, then you automatically purchase the security, and that is identical. As to whether the IRS (or your brokerage firm) recognizes the identical security when it falls out of an option, I can't say; but technically they could enforce it because the rule is based on 30 days and a \"\"substantially identical\"\" stock or security. In this interpretation (your investor) would probably at least want to stay out of the money in choosing a strike price, to avoid exercise; however, options are normally either held or sold, rather than be exercised, until at or very close to the expiration date (because time value is left on the table otherwise). So the key driver in this interpretation would be expiration date, which should be at least 31 days out from the stock sale; and it would be prudent to sell an out of the money put as well, in order to avoid the wash sale trigger. However there is also a more unfavorable opinion - see fairmark.com/capgain/wash/wsoption.htm where they hold that a \"\"deep in the money\"\" option is an immediate trigger (regardless of exercise). This article is sage, in that they say that the Treasury (IRS) may interpret an option transaction as a wash if it's ballpark to being exercisable. And, if the IRS throws paper, it always beats each of paper, rock and scissors :( A Schwab article (\"\"A Primer on Wash Sales\"\") says, if the CUSIPs match, bang, wash. This is the one that they may interpret unfavorably on in any case, supporting Schwab's \"\"play it safe\"\" position: \"\"3. Acquire a contract or option to buy substantially identical stock or securities...\"\" . This certainly nails buying a call. As to selling a put, well, it is at least conceivable that an IRS official would call that a contract to buy! SO it's simply not a slam dunk; there are varying opinions that you might describe as ranging from \"\"hell no\"\" to \"\"only if blatant.\"\" If you can get an \"\"official\"\" predetermination, or you like to go aggressive in your tax strategy, there's that; they may act adversely, so Caveat Taxfiler!\"",
"title": ""
},
{
"docid": "535605",
"text": "You have a lot of different questions in your post - I am only responding to the request for how to value the ESPP. When valuing an ESPP, don't think about what you might sell the shares for in the future, think about what the market would charge you for that option today. In general, an option is worth much less than the underlying share itself. For the simplest example, assume you work at a public company, and your exercise price for your options is $.30, and you can only exercise those options until the end of today, and the cost of the shares on the public stock exchange is also $.30. You have the same 'strike price' as everyone else in the market, making your option worth nothing. In truth, holding that right to a specific strike price into the future does give you value, because it means you can realize the upside in share price gains, without risking any money on share losses. So, how do you value the options? If it's a public company with an active options market, you can easily compare your $.30 strike price with the value of call options in the market that have a $.30 strike price. That becomes the value to you of the option (caveat: it is unlikely you can find an exact match for the terms of your vesting period, but you should be able to find a good starting point). If it's a public company without an active options market, you will have to do a bit of estimation. If a current share is worth $.25 (so, close to your strike price), then your option is worth a little bit, but not much. Compare other shares in your industry / company size to get examples of the relative value between an option and a share. If the current share price is worth $.35, then your option is worth about $.05 [the $.05 profit you could get by immediately exercising and selling, plus a bit more for an option on a share that you can't buy in the open market]. If it's a private company, then you need to be very clear on how shares are to be valued, and what methods you have available to sell back to the company / other individuals. You can then consider as per above, how to value the option for a share, vs the share itself. Without a clear way to sell your shares of a private company [ideally through a sale directly back to the company that you are able to force them to agree on; ie: the company will buyback shares at 5x Net income for the previous year, or something like that], then the value of a small number of shares is very nebulous. There is an extremely limited market for shares of private companies, if you don't own enough to exert control. In your case, because the valuation appears to be $2/share [be sure that these are the same share classes you have the option to buy], your option would be worth a little more than $1.70, if you didn't have to wait 4 years to exercise it. This would be total compensation of about $10k, if you were able to exercise today. Many people don't end up working for an early job in their career for 4 years, so you need to consider whether how much that will reduce the value of the ESPP for you personally. Compared with salary of 90k, 10k worth of stock in 4 years may not be a heavy motivating compensation consideration. Note also that because the company is not public, the valuation of $2/share should be taken with a grain of salt.",
"title": ""
},
{
"docid": "573077",
"text": "\"Being \"\"Long\"\" something means you own it. Being \"\"Short\"\" something means you have created an obligation that you have sold to someone else. If I am long 100 shares of MSFT, that means that I possess 100 shares of MSFT. If I am short 100 shares of MSFT, that means that my broker let me borrow 100 shares of MSFT, and I chose to sell them. While I am short 100 shares of MSFT, I owe 100 shares of MSFT to my broker whenever he demands them back. Until he demands them back, I owe interest on the value of those 100 shares. You short a stock when you feel it is about to drop in price. The idea there is that if MSFT is at $50 and I short it, I borrow 100 shares from my broker and sell for $5000. If MSFT falls to $48 the next day, I buy back the 100 shares and give them back to my broker. I pocket the difference ($50 - $48 = $2/share x 100 shares = $200), minus interest owed. Call and Put options. People manage the risk of owning a stock or speculate on the future move of a stock by buying and selling calls and puts. Call and Put options have 3 important components. The stock symbol they are actionable against (MSFT in this case), the \"\"strike price\"\" - $52 in this case, and an expiration, June. If you buy a MSFT June $52 Call, you are buying the right to purchase MSFT stock before June options expiration (3rd Saturday of the month). They are priced per share (let's say this one cost $0.10/share), and sold in 100 share blocks called a \"\"contract\"\". If you buy 1 MSFT June $52 call in this scenario, it would cost you 100 shares x $0.10/share = $10. If you own this call and the stock spikes to $56 before June, you may exercise your right to purchase this stock (for $52), then immediately sell the stock (at the current price of $56) for a profit of $4 / share ($400 in this case), minus commissions. This is an overly simplified view of this transaction, as this rarely happens, but I have explained it so you understand the value of the option. Typically the exercise of the option is not used, but the option is sold to another party for an equivalent value. You can also sell a Call. Let's say you own 100 shares of MSFT and you would like to make an extra $0.10 a share because you DON'T think the stock price will be up to $52/share by the end of June. So you go to your online brokerage and sell one contract, and receive the $0.10 premium per share, being $10. If the end of June comes and nobody exercises the option you sold, you get to keep the $10 as pure profit (minus commission)! If they do exercise their option, your broker makes you sell your 100 shares of MSFT to that party for the $52 price. If the stock shot up to $56, you don't get to gain from that price move, as you have already committed to selling it to somebody at the $52 price. Again, this exercise scenario is overly simplified, but you should understand the process. A Put is the opposite of a Call. If you own 100 shares of MSFT, and you fear a fall in price, you may buy a PUT with a strike price at your threshold of pain. You might buy a $48 June MSFT Put because you fear the stock falling before June. If the stock does fall below the $48, you are guaranteed that somebody will buy yours at $48, limiting your loss. You will have paid a premium for this right (maybe $0.52/share for example). If the stock never gets down to $48 at the end of June, your option to sell is then worthless, as who would sell their stock at $48 when the market will pay you more? Owning a Put can be treated like owning insurance on the stock from a loss in stock price. Alternatively, if you think there is no way possible it will get down to $48 before the end of June, you may SELL a $48 MSFT June Put. HOWEVER, if the stock does dip down below $48, somebody will exercise their option and force you to buy their stock for $48. Imagine a scenario that MSFT drops to $30 on some drastically terrible news. While everybody else may buy the stock at $30, you are obligated to buy shares for $48. Not good! When you sold the option, somebody paid you a premium for buying that right from you. Often times you will always keep this premium. Sometimes though, you will have to buy a stock at a steep price compared to market. Now options strategies are combinations of buying and selling calls and puts on the same stock. Example -- I could buy a $52 MSFT June Call, and sell a $55 MSFT June Call. I would pay money for the $52 Call that I am long, and receive money for the $55 Call that I am short. The money I receive from the short $55 Call helps offset the cost of buying the $52 Call. If the stock were to go up, I would enjoy the profit within in $52-$55 range, essentially, maxing out my profit at $3/share - what the long/short call spread cost me. There are dozens of strategies of mixing and matching long and short calls and puts depending on what you expect the stock to do, and what you want to profit or protect yourself from. A derivative is any financial device that is derived from some other factor. Options are one of the most simple types of derivatives. The value of the option is derived from the real stock price. Bingo? That's a derivative. Lotto? That is also a derivative. Power companies buy weather derivatives to hedge their energy requirements. There are people selling derivatives based on the number of sunny days in Omaha. Remember those calls and puts on stock prices? There are people that sell calls and puts based on the number of sunny days in Omaha. Sounds kind of ridiculous -- but now imagine that you are a solar power company that gets \"\"free\"\" electricity from the sun and they sell that to their customers. On cloudy days, the solar power company is still on the hook to provide energy to their customers, but they must buy it from a more expensive source. If they own the \"\"Sunny Days in Omaha\"\" derivative, they can make money for every cloudy day over the annual average, thus, hedging their obligation for providing more expensive electricity on cloudy days. For that derivative to work, somebody in the derivative market puts a price on what he believes the odds are of too many cloudy days happening, and somebody who wants to protect his interests from an over abundance of cloudy days purchases this derivative. The energy company buying this derivative has a known cost for the cost of the derivative and works this into their business model. Knowing that they will be compensated for any excessive cloudy days allows them to stabilize their pricing and reduce their risk. The person selling the derivative profits if the number of sunny days is higher than average. The people selling these types of derivatives study the weather in order to make their offers appropriately. This particular example is a fictitious one (I don't believe there is a derivative called \"\"Sunny days in Omaha\"\"), but the concept is real, and the derivatives are based on anything from sunny days, to BLS unemployment statistics, to the apartment vacancy rate of NYC, to the cost of a gallon of milk in Maine. For every situation, somebody is looking to protect themselves from something, and somebody else believes they can profit from it. Now these examples are highly simplified, many derivatives are highly technical, comprised of multiple indicators as a part of its risk profile, and extremely difficult to explain. These things might sound ridiculous, but if you ran a lemonade stand in Omaha, that sunny days derivative just might be your best friend...\"",
"title": ""
},
{
"docid": "120611",
"text": "(Note: I am omitting the currency units. While I strongly suspect it's US$ I don't know from the chart. The system works the same no matter what the currency.) A call or a put is the right to sell (put) or buy (call) shares at a certain price on a certain day. This is why you see a whole range of prices. Not all possible stock values are represented, the number of possibilities has to be kept reasonable. In this case the choices are even units, for an expensive stock they may be spaced even farther apart than this. The top of the chart says it's for June. It's actually the third Friday in the month, June 15th in this case. Thus these are bets on how the stock will move in the next 10 days. While the numbers are per share you can only trade options in lots of 100. The left side of the chart shows calls. Suppose you sell a call at 19 (the top of the chart) The last such trade would have gotten you a premium of 9.70 per share (the flip side of this is when the third friday rolls around it will most likely be exercised and they'll be paying you only 19 a share for a stock now trading at something over 26.) Note the volume, bid and ask columns though--you're not going to get 9.70 for such a call as there is no buyer. The most anybody is offering at present is 7.80 a share. Now, lets look farther down in the chart--say, a strike price of 30. The last trade was only .10--people think it's very unlikely that FB will rise above 30 to make this option worthwhile and thus you get very little for being willing to sell at that price. If FB stays at 26 the option will expire worthless and go away. If it's up to 31 when the 15th rolls around they'll exercise the option, take your shares and pay you 30 for them. Note that you already gave permission for the trade by selling the call, you can't back out later if it becomes a bad deal. Going over to the other side of the chart with the puts: Here the transaction goes the other way, come the 15th they have the option of selling you the shares for the strike price. Lets look at the same values we did before. 19? There's no trading, you can't do it. 30? Here you will collect 3.20 for selling the put. Come the 15th they have the right to sell you the stock for 30 a share. If it's still 26 they're certainly going to do so, but if it's up to 31 it's worthless and you pocket the 3.20 Note that you will normally not be allowed to sell a call if you don't own the shares in question. This is a safety measure as the risk in selling a call without the stock is infinite. If the stock somehow zoomed up to 10,000 when the 15th rolls around you would have to come up with the shares and the only way you could get them is buy them on the open market--you would have to come up with a million dollars. If there simply aren't enough shares available to cover the calls the result is catastrophic--whoever owns the shares simply gets to dictate terms to you. (And in the days of old this sometimes happened.)",
"title": ""
},
{
"docid": "243714",
"text": "\"The answer to the question, can I exercise the option right away? depends on the exercise style of the particular option contract you are talking about. If it's an American-style exercise, you can exercise at any moment until the expiration date. If it's an European-style exercise, you can only exercise at the expiration date. According to the CME Group website on the FOPs on Gold futures, it's an American-style exercise (always make sure to double check this - especially in the Options on Futures world, there are quite a few that are European style): http://www.cmegroup.com/trading/metals/precious/gold_contractSpecs_options.html?optionProductId=192#optionProductId=192 So, if you wanted to, the answer is: yes, you can exercise those contracts before expiration. But a very important question you should ask is: should you? Option prices are composed of 2 parts: intrinsic value, and extrinsic value. Intrinsic value is defined as by how much the option is in the money. That is, for Calls, it's how much the strike is below the current underlying price; and for Puts, it's how much the strike is above the current underlying price. Extrinsic value is whatever amount you have to add to the intrinsic value, to get the actual price the option is trading at the market. Note that there's no negative intrinsic value. It's either a positive number, or 0. When the intrinsic value is 0, all the value of the option is extrinsic value. The reason why options have extrinsic value is because they give the buyer a right, and the seller, an obligation. Ie, the seller is assuming risk. Traders are only willing to assume obligations/risks, and give others a right, if they get paid for that. The amount they get paid for that is the extrinsic value. In the scenario you described, underlying price is 1347, call strike is 1350. Whatever amount you have paid for that option is extrinsic value (because the strike of the call is above the underlying price, so intrinsic = 0, intrinsic + extrinsic = value of the option, by definition). Now, in your scenario, gold prices went up to 1355. Now your call option is \"\"in the money\"\", that is, the strike of your call option is below the gold price. That necessarily means that your call option has intrinsic value. You can easily calculate how much: it has exactly $5 intrinsic value (1355 - 1350, undelrying price - strike). But that contract still has some \"\"risk\"\" associated to it for the seller: so it necessarily still have some extrinsic value as well. So, the option that you bought for, let's say, $2.30, could now be worth something like $6.90 ($5 + a hypothetical $1.90 in extrinsic value). In your question, you mentioned exercising the option and then making a profit there. Well, if you do that, you exercise your options, get some gold futures immediately paying $1350 for them (your strike), and then you can sell them in the market for $1355. So, you make $5 there (multiplied by the contract multiplier). BUT your profit is not $5. Here's why: remember that you had to buy that option? You paid some money for that. In this hypothetical example, you payed $2.30 to buy the option. So you actually made only $5 - $2.30 = $2.70 profit! On the other hand, you could just have sold the option: you'd then make money by selling something that you bought for $2.30 that's now worth $6.90. This will give you a higher profit! In this case, if those numbers were real, you'd make $6.90 - $2.30 = $4.60 profit, waaaay more than $2.70 profit! Here's the interesting part: did you notice exactly how much more profit you'd have by selling the option back to the market, instead of exercising it and selling the gold contracts? Exactly $1.90. Do you remember this number? That's the extrinsic value, and it's not a coincidence. By exercising an option, you immediately give up all the extrinsic value it has. You are going to convert all the extrinsic value into $0. So that's why it's not optimal to exercise the contract. Also, many brokers usually charge you much more commissions and fees to exercise an option than to buy/sell options, so there's that as well! Always remember: when you exercise an option contract, you immediately give up all the extrinsic value it has. So it's never optimal to do an early exercise of option contracts and individual, retail investors. (institutional investors doing HFT might be able to spot price discrepancies and make money doing arbitrage; but retail investors don't have the low commissions and the technology required to make money out of that!) Might also be interesting to think about the other side of this: have you noticed how, in the example above, the option started with $2.30 of extrinsic value, and then it had less, $1.90 only? That's really how options work: as the market changes, extrinsic value changes, and as time goes by, extrinsic value usually decreases. Other factors might increase it (like, more fear in the market usually bring the option prices up), but the passage of time alone will decrease it. So options that you buy will naturally decrease some value over time. The closer you are to expiration, the faster it's going to lose value, which kind of makes intuitive sense. For instance, compare an option with 90 days to expiration (DTE) to another with 10 DTE. One day later, the first option still has 89 DTE (almost the same as 90 DTE), but the other has 9 DTE - it relatively much closer to the expiration than the day before. So it will decay faster. Option buyers can protect their investment from time decay by buying longer dated options, which decay slower! edit: just thought about adding one final thought here. Probabilities. The strategy that you describe in your question is basically going long an OTM call. This is an extremely bullish position, with low probability of making money. Basically, for you to make money, you need two things: you need to be right on direction, and you need to be right on time. In this example, you need the underlying to go up - by a considerable amount! And you need this to happen quickly, before the passage of time will remove too much of the extrinsic value of your call (and, obviously, before the call expires). Benefit of the strategy is, in the highly unlikely event of an extreme, unanticipated move of the underlying to the upside, you can make a lot of money. So, it's a low probability, limited risk, unlimited profit, extremely bullish strategy.\"",
"title": ""
},
{
"docid": "260384",
"text": "\"Yes, you can insure against the fall in price of stock by purchasing a put option. You pay for a put and if the price of the share falls below the \"\"strike price\"\" of the put, then you can exercise the put. On exercise, the person who sold you the put contract agrees to buy the stock for the strike price, even though that strike price is higher than the market price. You can adjust the level of insurance by buying put options at higher or lower prices, or buying fewer put options than shares you own (leaving some shares uninsured). Alternatively, you can minimize your risk exposure by investing in an index or other fund, which gives you partial ownership in a large number of shares. That means on any given day, lots of shares do worse and lots of shares do better. You can reduce the need for insurance by purchasing a lower-risk, lower-growth financial product.\"",
"title": ""
},
{
"docid": "237499",
"text": "\"There are a few different \"\"kinds\"\" of implied volatility. They are all based on the IVs obtained from the option pricing model you use. (1) Basically, given a few different values (current stock price, time until expiration, right of option, exercise style, strike of the option, interest rates, dividends, etc), you can obtain the IV for a given option price. If you look at the bid of an option, you can calculate the IV for that bid. If you look at the ask, there's a different IV for the ask. You can then look at the mid price, then you have a different IV, and so on and so on. And that's for each strike, in each expiration cycle! So you have a ton of different IVs. (2) In many option trading platforms, you'll see another kind of IV: the IV for each specific expiration cycle. That's calculated based on some of the IVs I mentioned on topic (1). Some kind of aggregation (more on this later). (3) Finally, people often talk about \"\"the IV of stock XYZ\"\". That's, again, an aggregation calculated from many of the IVs mentioned on topic (1). Now, your question seems to be: which IVs, from which options, from which months, with which weight, are part of the expiration cycle IV or for the IV of the stock itself? It really depends on the trading platform you are talking about. But very frequently, people will use a calculation similar to how the CBOE calculates the VIX. Basically, the VIX is just like the IV described on topic (3) above, but specifically for SPX, the S&P 500 index. The very detailed procedure and formulas to calculate the VIX (ie, IV of SPX) is described here: http://cfe.cboe.com/education/vixprimer/about.aspx If you apply the same (or a similar) methodology to other stocks, you'll get what you could call \"\"the IV of stock XYZ\"\".\"",
"title": ""
},
{
"docid": "388571",
"text": "\"Number 2 cannot occur. You can buy the call back and sell the stock, but the broker won't force that #2 choice. To trade options, you must have a margin account. No matter how high the stock goes, once \"\"in the money\"\" the option isn't going to rise faster, so your margin % is not an issue. And your example is a bit troublesome to me. Why would a $120 strike call spike to $22 with only a month left? You've made the full $20 on the stock rise and given up any gain after that. That's all. The call owner may exercise at any time. Edit: @jaydles is right, there are circumstances where an option price can increase faster than the stock price. Options pricing generally follows the Black-Scholes model. Since the OP gave us the current stock price, option strike price, and time to expiration, and we know the risk free rate is <1%, you can use the calculator to change volatility. The number two scenario won't occur, however, because a covered call has no risk to the broker, they won't force you to buy the option back, and the option buyer has no motive to exercise it as the entire option value is time premium.\"",
"title": ""
},
{
"docid": "305676",
"text": "\"In general there are two types of futures contract, a put and call. Both contract types have both common sides of a transaction, a buyer and a seller. You can sell a put contract, or sell a call contract also; you're just taking the other side of the agreement. If you're selling it would commonly be called a \"\"sell to open\"\" meaning you're opening your position by selling a contract which is different from simply selling an option that you currently own to close your position. A put contract gives the buyer the right to sell shares (or some asset/commodity) for a specified price on a specified date; the buyer of the contract gets to put the shares on someone else. A call contract gives the buyer the right to buy shares (or some asset/commodity) for a specified price on a specified date; the buyer of the contract gets to call on someone for shares. \"\"American\"\" options contracts allow the buyer can exercise their rights under the contract on or before the expiration date; while \"\"European\"\" type contracts can only be exercised on the expiration date. To address your example. Typically for stock an option contract involves 100 shares of a stock. The value of these contracts fluctuates the same way other assets do. Typically retail investors don't actually exercise their contracts, they just close a profitable position before the exercise deadline, and let unprofitable positions expire worthless. If you were to buy a single call contract with an exercise price of $100 with a maturity date of August 1 for $1 per share, the contract will have cost you $100. Let's say on August 1 the underlying shares are now available for $110 per share. You have two options: Option 1: On August 1, you can exercise your contract to buy 100 shares for $100 per share. You would exercise for $10,000 ($100 times 100 shares), then sell the shares for $10 profit per share; less the cost of the contract and transaction costs. Option 2: Your contract is now worth something closer to $10 per share, up from $1 per share when you bought it. You can just sell your contract without ever exercising it to someone with an account large enough to exercise and/or an actual desire to receive the asset or commodity.\"",
"title": ""
},
{
"docid": "387801",
"text": "In the scenario you describe, and really, in any scenario, by the nature of how option contracts work: a higher strike put will necessarily be more expensive than the lower strike put (everything else being equal). the lower strike call will necessarily be more expensive than the higher strike call (everything else being equal). In put options, the buyer has the right to sell stock for the strike price. So the higher the strike price, the more money the buyer of the put option can make by selling the shares of stock at a higher price. In call options, it's the exact opposite: buyers of the call option have the right to buy stock at the strike price. The lower the strike price, the better for the buyer: they have the right to buy stock for a lower amount of money. So it must be worth more.",
"title": ""
},
{
"docid": "112321",
"text": "\"Simple answer: Breakeven is when the security being traded reaches a price equal to the cost of the option plus the option's strike price, assuming you choose to exercise it. So for example, if you paid $1.00 for,say, a call option with a strike price of $19.00, breakeven would be when the security itself reaches $20.00. That being said, I can't imagine why you'd \"\"close out a position\"\" at the breakeven point. You wouldn't make or lose money doing that, so it wouldn't be rational. Now, as the option approaches expiration, you may make adjustments to the position to reflect shifts in momentum of the stock. So, if it looks as though the stock may not reach the option strike price, you could close out the position and take your lumps. But if the stock has momentum that will carry it past the strike price by expiration, you may choose to augment your position with additional contracts, although this would obviously mean the new contracts would be priced higher, which raises your dollar cost basis, and this may not make much sense. Another option in this scenario is that if the stock is going to surpass strike price, it might be a good opportunity to buy additional calls with either later expiration dates or with higher strike prices, depending on how much higher you speculate the stock will climb. I've managed to make some money doing this, buying options with strike prices just a dollar or two higher (or lower when playing puts), because the premiums were (in my opinion) underpriced to the potential peak of the stock by the expiration date. Sometimes the new options were actually slightly cheaper than my original positions, so my dollar cost basis overall dropped somewhat, improving my profit percentages.\"",
"title": ""
},
{
"docid": "215118",
"text": "\"Bull means the investor is betting on a rising market. Puts are a type of stock option where the seller of a put option promises to buy 100 shares of stock from the buyer of the put option at a pre-agreed price called the strike price on any day before expiration day. The buyer of the put option does not have to sell (it is optional, thats why it is called buying an option). However, the seller of the put is required to make good on their promise to the buyer. The broker can require the seller of the put option to have a deposit, called margin, to help make sure that they can make good on the promise. Profit... The buyer can profit from the put option if the stock price moves down substantially. The buyer of the put option does not need to own the stock, he can sell the option to someone else. If the buyer of the put option also owns the stock, the put option can be thought of like an insurance policy on the value of the stock. The seller of the put option profits if the stock price stays the same or rises. Basically, the seller comes out best if they can sell put options that no one ends up using by expiration day. A spread is an investment consisting of buying one option and selling another. Let's put bull and put and spread together with an example from Apple. So, if you believed Apple Inc. AAPL (currently 595.32) was going up or staying the same through JAN you could sell the 600 JAN put and buy the 550 put. If the price rises beyond 600, your profit would be the difference in price of the puts. Let's explore this a little deeper (prices from google finance 31 Oct 2012): Worst Case: AAPL drops below 550. The bull put spread investor owes (600-550)x100 shares = $5000 in JAN but received $2,035 for taking this risk. EDIT 2016: The \"\"worst case\"\" was the outcome in this example, the AAPL stock price on options expiry Jan 18, 2013 was about $500/share. Net profit = $2,035 - $5,000 = -$2965 = LOSS of $2965 Best Case: AAPL stays above 600 on expiration day in JAN. Net Profit = $2,035 - 0 = $2035 Break Even: If AAPL drops to 579.65, the value of the 600 JAN AAPL put sold will equal the $2,035 collected and the bull put spread investor will break even. Commissions have been ignored in this example.\"",
"title": ""
},
{
"docid": "368543",
"text": "\"Writing a put for a stock means you are selling the right to sell you stock. Simply put (er no pun intended), \"\"writing put options\"\" means you are selling somebody else the right (a contract) to sell YOU a specific stock at a specific price before a specific date. I imagine the word \"\"write\"\" to refer to the physical act of creating a contract. The specific price is called the STRIKE and the specific date is the EXPIRATION. By \"\"writing a put\"\", you are agreeing to purchase the stock at a particular price (the STRIKE price) before the expiration. You get paid a fee, the \"\"premium\"\", for agreeing to purchase the stock at the strike price if asked to. If the holder of the contract decides to make you buy the stock at the strike price, you have to do it. If the stock never dips below the strike price, then the holder of the put contract (a contract you wrote), will never exercise their right because they'd lose money. But if the stock drops to zero, you could potentially lose up to your strike price (times the number of shares at stake), if the holder of the contract decides to exercise. Therefore, \"\"writing puts\"\" is a LONG position, meaning you stand to gain if the stock goes up. FYI - \"\"LONG\"\" refers direction (UP!), not duration.\"",
"title": ""
},
{
"docid": "388754",
"text": "\"The question you are asking concerns the exercise of a short option position. The other replies do not appear to address this situation. Suppose that Apple is trading at $96 and you sell a put option with a strike price of $95 for some future delivery date - say August 2016. The option contract is for 100 shares and you sell the contract for a premium of $3.20. When you sell the option your account will be credited with the premium and debited with the broker commission. The premium you receive will be $320 = 100 x $3.20. The commission you pay will depend on you broker. Now suppose that the price of Apple drops to $90 and your option is exercised, either on expiry or prior to expiry. Then you would be obliged to take delivery of 100 Apple shares at the contracted option strike price of $95 costing you $9,500 plus broker commission. If you immediately sell the Apple shares you have purchased under your contract obligations, then assuming you sell the shares at the current market price of $90 you would realise a loss of $500 ( = 100x($95-$90) )plus commission. Since you received a premium of $320 when you sold the put option, your net loss would be $500-$320 = $180 plus any commissions paid to your broker. Now let's look at the case of selling a call option. Again assume that the price of Apple is $96 and you sell a call option for 100 shares with a strike price of $97 for a premium of $3.60. The premium you receive would be $360 = 100 x $3.60. You would also be debited for commission by your broker. Now suppose that the price of Apple shares rises to $101 and your option is exercised. Then you would be obliged to deliver 100 Apple shares to the party exercising the option at the contracted strike price of $97. If you did not own the shares to effect delivery, then you would need to purchase those shares in the market at the current market price of $101, and then sell them to the party exercising the option at the strike price of $97. This would realise an immediate loss of $400 = 100 x ($101-$97) plus any commission payable. If you did own the shares, then you would simply deliver them and possibly pay some commission or a delivery fee to your broker. Since you received $360 when you sold the option, your net loss would be $40 = $400-$360 plus any commission and fees payable to the broker. It is important to understand that in addition to these accounting items, short option positions carry with them a \"\"margin\"\" requirement. You will need to maintain a margin deposit to show \"\"good faith\"\" so long as the short option position is open. If the option you have sold moves against you, then you will be called upon to put up extra margin to cover any potential losses.\"",
"title": ""
},
{
"docid": "453582",
"text": "\"Investopedia explains how a stock split impacts the stock's options: Each option contract is typically in control of 100 shares of an underlying security at a predetermined strike price. To find the new coverage of the option, take the split ratio and multiply by the old coverage (normally 100 shares). To find the new strike price, take the old strike price and divide by the split ratio. Say, for example, you own a call for 100 shares of XYZ with a strike price of $75. Now, if XYZ had a stock split of 2 for 1, then the option would now be for 200 shares with a strike price of $37.50. If, on the other hand, the stock split was 3 for 2, then the option would be for 150 shares with a strike price of $50. So, yes, a 2 for 1 stock split would halve the option strike prices. Also, in case the Investopedia article isn't clear, after a split the options still control 100 shares per contract. Regarding how a dividend affects option prices, I found an article with a good explanation: As mentioned above, dividends payment could reduce the price of a stock due to reduction of the company's assets. It becomes intuitive to know that if a stock is expected to go down, its call options will drop in extrinsic value while its put options will gain in extrinsic value before it happens. Indeed, dividends deflate the extrinsic value of call options and inflate the extrinsic value of put options weeks or even months before an expected dividend payment. Extrinsic value of Call Options are deflated due to dividends not only because of an expected reduction in the price of the stock but also due to the fact that call options buyers do not get paid the dividends that the stock buyers do. This makes call options of dividend paying stocks less attractive to own than the stocks itself, thereby depressing its extrinsic value. How much the value of call options drop due to dividends is really a function of its moneyness. In the money call options with high delta would be expected to drop the most on ex-date while out of the money call options with lower delta would be least affected. If a stock is expected to drop by a certain amount, that drop would already have been priced into the extrinsic value of its put options way beforehand. This is what happens to put options of dividend paying stocks. This effect is again a function of options moneyness but this time, in the money put options raise in extrinsic value more than out of the money put options. This is because in the money put options with delta of close to -1 would gain almost dollar or dollar on the drop of a stock. As such, in the money put options would rise in extrinsic value almost as much as the dividend rate itself while out of the money put options may not experience any changes since the dividend effect may not be strong enough to bring the stock down to take those out of the money put options in the money. So, no, a dividend of $1 will not necessarily decrease an option's price by $1 on the ex-dividend date. It depends on whether it's a call or put option, and whether the option is \"\"in the money\"\" or \"\"out of the money\"\" and by how much.\"",
"title": ""
},
{
"docid": "318718",
"text": "Hi. Straddle: Buy a call and a put with an identical strike price. The strike is the price at which you can exercise the option. You pay a premium (cash) to buy the options. Typically you need a large amount of volatility in pricing movement in order to breakeven on the combined premium paid. Strangle: Purchasing a call and a put option with a non-identical strike price. Once again it is a volatility trading play. You need some type of price movement in the underlying security in order to break even or profit on the trade.",
"title": ""
},
{
"docid": "340730",
"text": "When your options vest, you will have the option to buy your company's stock at a particular price (the strike price). A big part of the value of the option is the difference between the price that your company's stock is trading at, and the strike price of the option. If the price of the company stock in the market is lower than the strike price of the option, they are almost worthless. I say 'almost' because there is still the possibility that the stock price could go up before the options expire. If your company is big enough that their stock is not only listed on an exchange, but there is an active options market in your company's stock, you could get a feel for what they are worth by seeing what the market is willing to buy or sell similar exchange listed options. Once the options have vested, you now have the right to purchase your company's stock at the specified strike price until the options expire. When you use that right, you are exercising the option. You don't have to do that until you think it is worthwhile buying company stock at that price. If the company pays a dividend, it would probably be worth exercising the options sooner, (options don't receive a dividend). Ultimately you are buying your company's stock (albeit at a discount). You need to see if your company's stock is still a good investment. If you think your company has growth prospects, you might want to hold onto the stock. If you think you'd be better off putting your money elsewhere in the market, sell the stock you acquired at a discount and use the money to invest in something else. If there are any additional benefits to holding on to the stock for a period of time (e.g. selling part to fit within your capital gain allowance for that year) you should factor that into your investment decision, but it shouldn't force you to invest in, or remain invested in something you would otherwise view as too risky to invest in. A reminder of that fact is that some employees of Enron invested their entire retirement plans into Enron stock, so when Enron went bankrupt, these employees not only lost their job but their savings for retirement as well...",
"title": ""
},
{
"docid": "257609",
"text": "If the call is in the money and you believe the reason for the price jump was an overreaction with a pullback on the horizon or you anticipate downward movement for other reasons, I will roll (sometimes for a strike closer to at the money) as long as the trade results in a net credit! You already have the statistical edge trading covered calls over everyone who purchased stock at the same point in time. This is because covered calls reduce your cost basis and increase your probability of profit. For people reading this who are not interested in the math behind probability of profit(POP) for covered calls, you should be aware of why POP is higher for covered calls (CC). With CCs you win when the stock price stays the same, you win when it goes down slightly, you win when the stock goes up. You have two more ways to win than someone who just buys stock, therefore a higher probability of making a buck! Another option: If your stock is going to be called at a loss, or the strike you want to roll to results in a net debit, or your cash funds are short of owning 100x shares and you are familiar with the stock, try writing a naked put for the price you want to buy at. At experation, if the naked put is exercised, your basis is reduced by the premium of the put you sold, and you can write a covered call against the stock you now own. If it expires worthless you keep the premium. This is also another way to increase your POP.",
"title": ""
}
] |
PLAIN-3072
|
Avoiding a Sugary Grave
|
[
{
"docid": "MED-4553",
"text": "Alzheimer's disease (AD) is the most common dementing disorder of late life. Although there might be various different triggering events in the early stages of the disease, they seem to converge on a few characteristic final pathways in the late stages, characterized by inflammation and neurodegeneration. In this review, we put forward the hypothesis that advanced glycation end products (AGEs) and their precursors, including methylglyoxal, are both biomarkers and causative agents (\"gerontotoxins\") characteristic for this disorder. Accumulation of AGEs is a normal feature of aging, but is accelerated in AD, where AGEs can be detected in amyloid plaques and neurofibrillary tangles. AGE modification may explain many of the neuropathological and biochemical features of AD such as extensive protein cross-linking, inflammation, oxidative stress and neuronal cell death. We suggest that methylglyoxal is one of the major carbonyl species responsible for the formation of AGEs. We propose that one promising pharmacological approach to prevent the formation of AGEs would be to lower the methylglyoxal concentration. This can be achieved, for example, by decreasing the concentration of methylglyoxal precursors such as d-glyceraldehyde-3-phosphate by allowing a higher flux through the pentose phosphate pathway or by increasing methylglyoxal detoxification through the glyoxalase system. Alternatively, methylglyoxal could be scavenged by various types of carbonyl scavengers. Copyright © 2010 Elsevier Inc. All rights reserved.",
"title": "Advanced glycation end products as biomarkers and gerontotoxins - A basis to explore methylglyoxal-lowering agents for Alzheimer's disease?"
}
] |
[
{
"docid": "MED-4028",
"text": "This paper aims to provide dental health professionals with practical advice to pass on to patients about diet and dental health. Sugars are the most important dietary factor contributing to dental caries. Different foods carry different dental health risks; those containing non-milk, extrinsic sugars are potentially the most damaging. In the UK, sugared soft drinks and confectionery contribute approximately 50% to total intake of non-milk extrinsic sugars. Patients should be encouraged to reduce the frequency of intake of sugary foods. Intake of acidic foods and drinks contributes to dental erosion and consumption of such foods should also be limited. Dietary advice to dental patients should be positive and personalized if possible and can be in line with dietary recommendations for general health. These are to increase the consumption of starchy staple foods (eg bread, potatoes and unsweetened cereals), vegetables and fruit and to reduce the consumption of sugary and fatty foods.",
"title": "Dietary advice in dental practice."
},
{
"docid": "MED-2351",
"text": "Anti-Gal is a natural Ab abundantly produced in humans. It interacts specifically with the carbohydrate epitope Gal alpha 1-3Gal beta 1-4GlcNAc-R (termed the alpha-galactosyl epitope). This epitope is expressed in large amounts on thyrocytes of nonprimate mammals, but not of humans. We have previously found that binding of anti-Gal to alpha-galactosyl epitopes on porcine thyrocytes results in stimulatory effects similar to those exerted by thyroid-stimulating hormone (thyrotropin). In the present study, we tested the hypothesis that anti-Gal may contribute to Graves' disease (GD) pathogenesis by stimulation of the thyrocytes of patients with this autoimmune disorder. Anti-Gal binding and stimulatory effects were assessed in primary thyrocyte cultures. Anti-Gal specifically bound to GD thyrocytes and induced an increase in cAMP synthesis, 125I uptake, and DNA synthesis in these cells. Furthermore, the stimulatory effects of autologous sera on GD thyrocytes were greatly reduced after specific depletion of anti-Gal from these sera. No binding and no stimulatory effects of anti-Gal were observed, however, with normal human thyrocytes and with thyrocytes from thyrotoxic patients who lack thyroid-stimulating Igs or thyrotropin binding inhibiting Igs. These in vitro stimulatory effects of anti-Gal on GD thyrocytes suggest that this natural Ab may contribute to the in vivo continuous stimulation of thyrocytes in GD patients. The possibility that anti-Gal may stimulate GD thyrocytes via interaction with aberrantly expressed alpha-galactosyl epitopes on the thyroid-stimulating hormone receptor is discussed.",
"title": "Specific stimulation of Graves' disease thyrocytes by the natural anti-Gal antibody from normal and autologous serum."
},
{
"docid": "MED-4133",
"text": "BACKGROUND: Yersinia enterocolitica (YE) infection has long been implicated in the pathogenesis of Graves' disease (GD). The association between YE and GD could, however, also be due to common genetic or environmental factors affecting the development of both YE infection and GD. This potential confounding can be minimized by investigation of twin pairs discordant for GD. AIM: To examine whether YE infection is associated with GD. DESIGN: We first conducted a classical case-control study of individuals with (61) and without (122) GD, and then a case-control study of twin pairs (36) discordant for GD. METHODS: Immunoglobulin (Ig)A and IgG antibodies to virulence-associated Yersinia outer membrane proteins (YOPs) were measured. MAIN OUTCOME MEASURES: The prevalence of YOP IgA and IgG antibodies. RESULTS: Subjects with GD had a higher prevalence of YOP IgA (49%vs. 34%, P = 0.054) and YPO IgG (51%vs. 35%, P = 0.043) than the external controls. The frequency of chronic YE infection, reflected by the presence of both IgA and IgG YOP antibodies, was also higher among cases than controls (49%vs. 33%, P = 0.042). Similar results were found in twin pairs discordant for GD. In the case-control analysis, individuals with GD had an increased odds ratio (OR) of YE infection: IgA 1.84 (95% CI 0.99-3.45) and IgG 1.90 (95% CI 1.02-3.55). In the co-twin analysis, the twin with GD also had an increased OR of YE infection: IgA 5.5 (95% CI 1.21-24.81) and IgG 5.0 (95% CI 1.10-22.81). CONCLUSION: The finding of an association between GD and YE in the case-control study and within twin pairs discordant for GD supports the notion that YE infection plays an aetiological role in the occurrence of GD, or vice versa. Future studies should examine the temporal relationship of this association in more depth.",
"title": "Too early to dismiss Yersinia enterocolitica infection in the aetiology of Graves' disease: evidence from a twin case-control study."
},
{
"docid": "MED-4600",
"text": "Enough solid evidence now exists to offer women several fundamental strategies for healthy eating. They include emphasizing healthful unsaturated fats, whole grains, good protein “packages,” and fruits and vegetables; limiting consumption of trans and saturated fats, highly refined grains, and sugary beverages; and taking a multivitamin with folic acid and extra vitamin D as a nutritional safety net. A diet based on these principles is healthy through virtually all life stages, from young adulthood through planning for pregnancy, pregnancy, and on into old age.",
"title": "Essentials of Healthy Eating: A Guide"
},
{
"docid": "MED-1534",
"text": "To determine whether realistic snacks containing added sugar evoke excessive insulin responses, 10 healthy subjects consumed four different snack meals, similar in fat and total energy content. Two snacks were based on sugary, manufactured products (chocolate-coated candy bar; cola drink with crisps) and two on whole foods (raisins and peanuts; bananas and peanuts). After the processed-food snacks, plasma-glucose levels tended to rise higher and to fall lower than after the whole-food snacks. The area under the plasma insulin curve was 70% greater after the manufactured snacks than after the raisin-peanut snack. The banana-peanut snack evoked an intermediate insulin response. One subject had pathological insulinaemia after both manufactured snacks but normal responses after both whole-food snacks. These findings suggest that foods and drinks containing added fiber-depleted sugars stress and sometimes overwhelm homeostatic mechanisms but also suggest that the insulin response to food is influenced by the physical state of the food.",
"title": "Glucose and insulin responses to manufactured and whole-food snacks."
},
{
"docid": "MED-4663",
"text": "Hyperthyroidism results from excessive production of thyroid hormones. This is usually caused by Graves disease, but exogenous thyroid hormones can lead to similar symptoms. Recognition of the latter is difficult as excessive intake of thyroid hormone is not usually admitted nor recognised. To our knowledge, exogenous hyperthyroidism caused by thyroid-contaminated food has been described twice, but not in the Netherlands. A 77-year-old man presented at the Outpatient Department of Internal Medicine with lab values revealing hyperthyroidism. There were no abnormal findings at the physical examination. Antibodies against the thyroidstimulating hormone (TSH) receptor were not detectable. Thyroid scintigraphy with 123I showed an uptake of less than 1%. Silent thyroiditis was diagnosed and the natural course was awaited, but with no improvement in the thyroid values. The thyroglobulin was very low. Further anamnesis revealed an excessive daily consumption of sausages. Thyroid hormones were detectable in these sausages. After the patient stopped eating them, he became and remained euthyroid. The case stipulates the importance of a thorough anamnesis.",
"title": "Hyperthyroidism caused by excessive consumption of sausages."
},
{
"docid": "MED-1814",
"text": "Pancreatic cancer is highly lethal, and identifying modifiable risk factors could have substantial public health impact. In this population-based case-control study (532 cases, 1701 controls), we used principal component analysis and multivariable unconditional logistic regression models to examine whether a particular dietary pattern was associated with risk of pancreatic cancer, adjusting for other known risk factors. A Prudent dietary pattern, characterized by greater intake of vegetables, fruit, fish, poultry, whole grains, and low-fat dairy, was associated with an approximate 50% reduction in pancreatic cancer risk among men (OR=0.51, 95% CI 0.31-0.84, p-trend=0.001) and women (OR=0.51, 95% CI 0.29-0.90, p-trend=0.04). A Western dietary pattern, characterized by higher intake of red and processed meats, potato chips, sugary beverages, sweets, high fat dairy, eggs, and refined grains, was associated with a 2.4-fold increased risk of pancreatic cancer among men (95% CI 1.3-4.2, p-trend=0.008); but was not associated with risk among women. Among men, those in the upper quintiles of the Western diet and lower quintiles of the Prudent diet had a 3-fold increased risk. Consistent with what has been recommended for several other chronic diseases, consuming a diet rich in plant-based foods, whole grains, and white meat, might reduce risk of pancreatic cancer.",
"title": "Dietary patterns and risk of pancreatic cancer in a large population-based case-control study in the San Francisco Bay Area"
},
{
"docid": "MED-2366",
"text": "Glycoconjugates and their antibodies are vital components of host-tumor interaction. This review concentrates on the oncological implications of research concerning the alpha gal triad; the alpha 1-->3 galactosyl epitope (alpha Gal), the enzyme responsible for its construction, alpha 1,3 galactosyl transferase (alpha 1-3GT), and its associated antibody: anti-gal. Alpha gal epitopes, previously assumed to be absent from human tissue, have been demonstrated on several human cancer cell lines, senescent red blood cells, and Graves' disease thyrocytes. Alpha-gal presence on neoplastic lines is correlated with increased metastatic formation in animal models. The mechanisms of human response to these neoantigens are complex, as natural anti-gal antibodies exist in high titers in normal sera, thus predicting immunological recognition of cells expressing alpha gal epitopes. Hypotheses vary regarding the pathogenic contributions of metastasis-associated phenomena such as de novo expression of alpha gal and its unmasking by desialylation. The means by which alpha gal is sporadically expressed in human tissue remain unknown, as the galactosyl transferase which produces this epitope in constitutively expressive animals has undergone significant mutation at the genomic level in humans. Pathological re-expression is presumed to require permissive changes at a cellular level. Detailing these alterations is a prerequisite to the comprehension of the metastatic phenotype. In this context, the possibility of therapeutic strategies affecting alpha gal expression are also discussed.",
"title": "A possible role for the alpha 1-->3 galactosyl epitope and the natural anti-gal antibody in oncogenesis."
},
{
"docid": "MED-2353",
"text": "Summary Anti-Gal is the most abundant natural antibody in humans, constituting ∼ 1% of immunoglobulins. Anti-Gal is naturally produced also in apes and Old World monkeys. The ligand of anti-Gal is a carbohydrate antigen called the ‘α-gal epitope’ with the structure Galα1-3Galβ1-4GlcNAc-R. The α-gal epitope is present as a major carbohydrate antigen in non-primate mammals, prosimians and New World monkeys. Anti-Gal can contributes to several immunological pathogeneses. Anti-Gal IgE produced in some individuals causes allergies to meat and to the therapeutic monoclonal antibody cetuximab, all presenting α-gal epitopes. Aberrant expression of the α-gal epitope or of antigens mimicking it in humans may result in autoimmune processes, as in Graves' disease. α-Gal epitopes produced by Trypanosoma cruzi interact with anti-Gal and induce ‘autoimmune like’ inflammatory reactions in Chagas' disease. Anti-Gal IgM and IgG further mediate rejection of xenografts expressing α-gal epitopes. Because of its abundance, anti-Gal may be exploited for various clinical uses. It increases immunogenicity of microbial vaccines (e.g. influenza vaccine) presenting α-gal epitopes by targeting them for effective uptake by antigen-presenting cells. Tumour lesions are converted into vaccines against autologous tumour-associated antigens by intra-tumoral injection of α-gal glycolipids, which insert into tumour cell membranes. Anti-Gal binding to α-gal epitopes on tumour cells targets them for uptake by antigen-presenting cells. Accelerated wound healing is achieved by application of α-gal nanoparticles, which bind anti-Gal, activate complement, and recruit and activate macrophages that induce tissue regeneration. This therapy may be of further significance in regeneration of internally injured tissues such as ischaemic myocardium and injured nerves.",
"title": "Anti-Gal: an abundant human natural antibody of multiple pathogeneses and clinical benefits"
},
{
"docid": "MED-1055",
"text": "OBJECTIVE: To indicate why the world's most powerful nation state and one powerful sector of the food and drink production and manufacturing industry are determined to demolish the 2004 WHO (World Health Organization) global strategy on diet, physical activity and health, and to disassociate it from the 2003 WHO/FAO (Food and Agriculture Organization) expert report on diet, nutrition and the prevention of chronic diseases, which with its background papers is the immediate scientific basis for the strategy. To encourage representatives of nation states at the 2004 WHO World Health Assembly to support the strategy together with the report, so that the strategy is explicit and quantified, and responds to the need expressed by member states at the 2002 World Health Assembly. This is for an effective global strategy to prevent and control chronic diseases whose prevalence is increased by nutrient-poor food low in vegetables and fruits and high in energy-dense fatty, sugary and/or salty foods and drinks and also by physical inactivity. Of these diseases, obesity, diabetes, cardiovascular diseases and cancers of several sites are now the chief causes of morbidity and mortality in most countries in the world. METHOD: A summary of the global strategy and its roots in scientific knowledge accumulated over the last half-century. Reasons why the global strategy and the expert report are opposed by the current US government and the world sugar industry, with some reference to modern historical context. A summary of the trajectory of the global strategy since its first draft made in early 2003, and a further summary of its weaknesses, strengths and potential. CONCLUSION: The 2004 WHO global strategy and the 2003 WHO/FAO expert report are perceived by the current US administration as an impediment to US trade and international policy, within a general context of current US government hostility to the UN (United Nations) system as a brake on the exercise of its power as the world's dominant nation. Policy-makers throughout the world should be aware of the contexts of current pressures put on them by powerful nation states and sectors of industry whose ideologies and commercial interests are challenged by international initiatives designed to improve public health and to leave a better legacy for future generations.",
"title": "Why the Bush administration and the global sugar industry are determined to demolish the 2004 WHO global strategy on diet, physical activity and he..."
},
{
"docid": "MED-4612",
"text": "Amino acids modulate the secretion of both insulin and glucagon; the composition of dietary protein therefore has the potential to influence the balance of glucagon and insulin activity. Soy protein, as well as many other vegan proteins, are higher in non-essential amino acids than most animal-derived food proteins, and as a result should preferentially favor glucagon production. Acting on hepatocytes, glucagon promotes (and insulin inhibits) cAMP-dependent mechanisms that down-regulate lipogenic enzymes and cholesterol synthesis, while up-regulating hepatic LDL receptors and production of the IGF-I antagonist IGFBP-1. The insulin-sensitizing properties of many vegan diets--high in fiber, low in saturated fat--should amplify these effects by down-regulating insulin secretion. Additionally, the relatively low essential amino acid content of some vegan diets may decrease hepatic IGF-I synthesis. Thus, diets featuring vegan proteins can be expected to lower elevated serum lipid levels, promote weight loss, and decrease circulating IGF-I activity. The latter effect should impede cancer induction (as is seen in animal studies with soy protein), lessen neutrophil-mediated inflammatory damage, and slow growth and maturation in children. In fact, vegans tend to have low serum lipids, lean physiques, shorter stature, later puberty, and decreased risk for certain prominent 'Western' cancers; a vegan diet has documented clinical efficacy in rheumatoid arthritis. Low-fat vegan diets may be especially protective in regard to cancers linked to insulin resistance--namely, breast and colon cancer--as well as prostate cancer; conversely, the high IGF-I activity associated with heavy ingestion of animal products may be largely responsible for the epidemic of 'Western' cancers in wealthy societies. Increased phytochemical intake is also likely to contribute to the reduction of cancer risk in vegans. Regression of coronary stenoses has been documented during low-fat vegan diets coupled with exercise training; such regimens also tend to markedly improve diabetic control and lower elevated blood pressure. Risk of many other degenerative disorders may be decreased in vegans, although reduced growth factor activity may be responsible for an increased risk of hemorrhagic stroke. By altering the glucagon/insulin balance, it is conceivable that supplemental intakes of key non-essential amino acids could enable omnivores to enjoy some of the health advantages of a vegan diet. An unnecessarily high intake of essential amino acids--either in the absolute sense or relative to total dietary protein--may prove to be as grave a risk factor for 'Western' degenerative diseases as is excessive fat intake.",
"title": "Vegan proteins may reduce risk of cancer, obesity, and cardiovascular disease by promoting increased glucagon activity."
},
{
"docid": "MED-1162",
"text": "Consumers are frequently urged to avoid imported foods as well as specific fruits and vegetables due to health concerns from pesticide residues and are often encouraged to choose organic fruits and vegetables rather than conventional forms. Studies have demonstrated that while organic fruits and vegetables have lower levels of pesticide residues than do conventional fruits and vegetables, pesticide residues are still frequently detected on organic fruits and vegetables; typical dietary consumer exposure to pesticide residues from conventional fruits and vegetables does not appear to be of health significance. Similarly, research does not demonstrate that imported fruits and vegetables pose greater risks from pesticide residues than do domestic fruits and vegetables or that specific fruits and vegetables singled out as being the most highly contaminated by pesticides should be avoided in their conventional forms.",
"title": "Pesticide residues in imported, organic, and \"suspect\" fruits and vegetables."
},
{
"docid": "MED-5297",
"text": "Nineteen unselected patients with mild to moderate essential hypertension, whose average supine blood pressure after two months' observation on no treatment was 156/98 mm Hg, were advised not to add salt to food and to avoid sodium-laden foods. After 2 weeks of sodium restriction patients were entered into an 8-week double-blind randomised crossover study of 'Slow Sodium' (Ciba) versus slow sodium placebo. The mean supine blood pressure was 7.1 mm Hg (6.1%) lower in the fourth week of placebo than that in the fourth week of slow sodium (p less than 0.001). Urinary sodium excretion in the fourth week of slow sodium was 162 +/- 9 mmol/24 h and that in the fourth week of placebo was 86 mmol +/- 9 mmol/24 h (p less than 0.001). There was no difference in potassium excretion. These results suggest that moderate sodium restriction achieved by not adding salt and avoiding sodium-laden foods should, if not already, become part of the management of essential hypertension.",
"title": "Double-blind randomised crossover trial of moderate sodium restriction in essential hypertension."
},
{
"docid": "MED-1552",
"text": "OBJECTIVE: To determine the quantitative importance of dietary fatty acids and dietary cholesterol to blood concentrations of total, low density lipoprotein, and high density lipoprotein cholesterol. DESIGN: Meta-analysis of metabolic ward studies of solid food diets in healthy volunteers. SUBJECTS: 395 dietary experiments (median duration 1 month) among 129 groups of individuals. RESULTS: Isocaloric replacement of saturated fats by complex carbohydrates for 10% of dietary calories resulted in blood total cholesterol falling by 0.52 (SE 0.03) mmol/l and low density lipoprotein cholesterol falling by 0.36 (0.05) mmol/l. Isocaloric replacement of complex carbohydrates by polyunsaturated fats for 5% of dietary calories resulted in total cholesterol falling by a further 0.13 (0.02) mmol/l and low density lipoprotein cholesterol falling by 0.11 (0.02) mmol/l. Similar replacement of carbohydrates by monounsaturated fats produced no significant effect on total or low density lipoprotein cholesterol. Avoiding 200 mg/day dietary cholesterol further decreased blood total cholesterol by 0.13 (0.02) mmol/l and low density lipoprotein cholesterol by 0.10 (0.02) mmol/l. CONCLUSIONS: In typical British diets replacing 60% of saturated fats by other fats and avoiding 60% of dietary cholesterol would reduce blood total cholesterol by about 0.8 mmol/l (that is, by 10-15%), with four fifths of this reduction being in low density lipoprotein cholesterol.",
"title": "Dietary lipids and blood cholesterol: quantitative meta-analysis of metabolic ward studies."
},
{
"docid": "MED-5134",
"text": "This position paper on complementary feeding summarizes evidence for health effects of complementary foods. It focuses on healthy infants in Europe. After reviewing current knowledge and practices, we have formulated these conclusions: Exclusive or full breast-feeding for about 6 months is a desirable goal. Complementary feeding (ie, solid foods and liquids other than breast milk or infant formula and follow-on formula) should not be introduced before 17 weeks and not later than 26 weeks. There is no convincing scientific evidence that avoidance or delayed introduction of potentially allergenic foods, such as fish and eggs, reduces allergies, either in infants considered at increased risk for the development of allergy or in those not considered to be at increased risk. During the complementary feeding period, >90% of the iron requirements of a breast-fed infant must be met by complementary foods, which should provide sufficient bioavailable iron. Cow's milk is a poor source of iron and should not be used as the main drink before 12 months, although small volumes may be added to complementary foods. It is prudent to avoid both early (<4 months) and late (>or=7 months) introduction of gluten, and to introduce gluten gradually while the infant is still breast-fed, inasmuch as this may reduce the risk of celiac disease, type 1 diabetes mellitus, and wheat allergy. Infants and young children receiving a vegetarian diet should receive a sufficient amount ( approximately 500 mL) of breast milk or formula and dairy products. Infants and young children should not be fed a vegan diet.",
"title": "Complementary feeding: a commentary by the ESPGHAN Committee on Nutrition."
},
{
"docid": "MED-2014",
"text": "BACKGROUND: Gastrointestinal symptoms that respond to the removal of wheat and/or gluten are becoming more common. Patients who avoid wheat and/or gluten (PWAWG) are a heterogeneous group and predominantly self-diagnosed prior to presenting for clinical evaluation. SPECIFIC AIM: We characterized PWAWGs seen at a tertiary care referral center and compared them to patients with celiac disease (CD) and subjects in the National Health and Nutrition examination survey (NHANES). METHODS: This was a cross-sectional study evaluating patients seen by four gastroenterologists at a CD referral center. Baseline characteristics, laboratory values, and medical comorbidities were compared to CD patients who presented at the same center and subjects enrolled in NHANES. RESULTS: Eighty-four PWAWGs were identified and compared to 585 CD patients and 2,686 NHANES patients. Thirty-two alternative diagnoses were made in 25 (30%) PWAWGs, including small intestinal bacterial overgrowth and fructose/lactose intolerance. When compared to patients with CD, PWAWGs had similar body mass index (BMI, 23.1 vs. 23.5, p = 0.54) and mean hemoglobin value (13.4 vs. 13.3, p = 0.6). When compared to male and female patients in NHANES, BMI, folate, and mean hemoglobin values were lower in PWAWGs. Both male and female PWAWGs had a lower prevalence of hypertension. CONCLUSION: While there are similarities between CD and PWAWGs that could possibly be due to shared HLA haplotypes or an effect of the gluten-free diet, alternative diagnoses are common in these patients. PWAWGs have a similar cardiovascular profile as CD patients in terms of lower BMI and lower prevalence of hypertension.",
"title": "Characteristics of patients who avoid wheat and/or gluten in the absence of Celiac disease."
},
{
"docid": "MED-2036",
"text": "The prevalence of allergic-related diseases, food intolerance, and chemical sensitivities in both the pediatric and adult population has increased dramatically over the last two decades, with escalating rates of associated morbidity. Conditions of acquired allergy, food intolerance and chemical hypersensitivity are frequently the direct sequelae of a toxicant induced loss of tolerance (TILT) in response to a significant initiating toxic exposure. Following the primary toxicant insult, the individuals become sensitive to low levels of diverse and unrelated triggers in their environment such as commonly encountered chemical, inhalant or food antigens. Among sensitized individuals, exposure to assorted inciting stimuli may precipitate diverse clinical and/or immune sequelae as may be evidenced by clinical symptoms as well as varied lymphocyte, antibody, or cytokine responses in some cases. Recently recognized as a mechanism of disease development, TILT and resultant sensitivity-related illness (SRI) may involve various organ systems and evoke wide-ranging physical or neuropsychological manifestations. With escalating rates of toxicant exposure and bioaccumulation in the population-at-large, an increasing proportion of contemporary illness is the direct result of TILT and ensuing SRI. Avoidance of triggers will preclude symptoms, and desensitization immunotherapy or immune suppression may ameliorate symptomatology in some cases. Resolution of SRI generally occurs on a gradual basis following the elimination of bioaccumulated toxicity and avoidance of further initiating adverse environmental exposures. As has usually been the case throughout medical history whenever new evidence regarding disease mechanisms emerges, resistance to the translation of knowledge abounds. Copyright © 2010 Elsevier B.V. All rights reserved.",
"title": "Sensitivity-related illness: the escalating pandemic of allergy, food intolerance and chemical sensitivity."
},
{
"docid": "MED-3545",
"text": "Background Omnivorous diets are high in arachidonic acid (AA) compared to vegetarian diets. Research shows that high intakes of AA promote changes in brain that can disturb mood. Omnivores who eat fish regularly increase their intakes of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), fats that oppose the negative effects of AA in vivo. In a recent cross-sectional study, omnivores reported significantly worse mood than vegetarians despite higher intakes of EPA and DHA. This study investigated the impact of restricting meat, fish, and poultry on mood. Findings Thirty-nine omnivores were randomly assigned to a control group consuming meat, fish, and poultry daily (OMN); a group consuming fish 3-4 times weekly but avoiding meat and poultry (FISH), or a vegetarian group avoiding meat, fish, and poultry (VEG). At baseline and after two weeks, participants completed a food frequency questionnaire, the Profile of Mood States questionnaire and the Depression Anxiety and Stress Scales. After the diet intervention, VEG participants reduced their EPA, DHA, and AA intakes, while FISH participants increased their EPA and DHA intakes. Mood scores were unchanged for OMN or FISH participants, but several mood scores for VEG participants improved significantly after two weeks. Conclusions Restricting meat, fish, and poultry improved some domains of short-term mood state in modern omnivores. To our knowledge, this is the first trial to examine the impact of restricting meat, fish, and poultry on mood state in omnivores.",
"title": "Restriction of meat, fish, and poultry in omnivores improves mood: A pilot randomized controlled trial"
},
{
"docid": "MED-2709",
"text": "This systematic review aims to summarize all reported cases of cardiac tamponade after acupuncture. Five electronic databases and our own files were searched for reports of cardiac tamponade after acupuncture. No restrictions in time or language were imposed. Data were extracted by two independent reviewers according to predefined criteria. We found a total of 26 cases. In 14 patients, the complications were fatal. In most instances, there is little doubt about causality. We conclude that cardiac tamponade is a serious, often fatal complication after acupuncture. As it is theoretically avoidable, acupuncturists should be trained to minimize the risk. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.",
"title": "Cardiac tamponade caused by acupuncture: a review of the literature."
},
{
"docid": "MED-3204",
"text": "Grapefruit is a healthy addition to a well-balanced diet. However, the fruit has been shown to affect the metabolism of many medications, increasing the risk of toxicity and adverse effects. Characteristics of oral medications that may interact with grapefruit include extensive metabolism through the intestinal cytochrome P450 3A4 system, low bioavailability, and a narrow therapeutic index. Prominent medications known to interact with grapefruit include statins, antiarrhythmic agents, immunosuppressive agents, and calcium channel blockers. There are equally effective alternatives to these drug classes that do not have the potential to interact with grapefruit. These alternative drugs may be substituted if a patient experiences or is at risk of a grapefruit-drug interaction. Patients also may choose to exclude grapefruit from their diets and consume other fruits, including other types of citrus, to avoid an interaction.",
"title": "Management of grapefruit-drug interactions."
},
{
"docid": "MED-3351",
"text": "Based on evidence that the color red elicits avoidance motivation across contexts (Mehta & Zhu, 2009), two studies investigated the effect of the color red on snack food and soft drink consumption. In line with our hypothesis, participants drank less from a red labeled cup than from a blue labeled cup (Study 1), and ate less snack food from a red plate than from a blue or white plate (Study 2). The results suggest that red functions as a subtle stop signal that works outside of focused awareness and thereby reduces incidental food and drink intake. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "The color red reduces snack food and soft drink intake."
},
{
"docid": "MED-4739",
"text": "Contemporary reproductive aged women and their offspring are facing an unprecedented onslaught of toxicant exposures from myriad sources in their day-to-day life. Public health recommendations regarding optimal diet and nutrition in pregnancy must incorporate several considerations including safety of available foodstuffs, cultural practices and lifestyle issues. Gestational consumption of contaminated seafood remains a potential source of toxicant exposure, including mercury, for the developing child. Health care professionals responsible for the care of women and their developing children need to become apprised of: a) risks associated with toxicant bioaccumulation in pregnancy; b) ongoing information emerging in the important field of reproductive toxicology; and c) strategies within the clinical setting to facilitate nutritional sufficiency and precautionary avoidance of adverse exposure among young women.",
"title": "Nowhere to hide: Chemical toxicants and the unborn child."
},
{
"docid": "MED-5133",
"text": "We report the case of a 7 month-old girl that presented with acute anemia, generalized muscular hypotonia and failure to thrive. Laboratory evaluation revealed cobalamin deficiency, due to a vegan diet of the mother. The clinical triad of an acquired floppy baby syndrome with megaloblastic anemia and failure to thrive is pathognomic for infantile cobalamin deficiency. Neurological abnormalities are often irreversible and may be associated with delayed myelinization in the MRI. A normal cobalamin level in maternal serum and absence of anemia do not exclude subclinical deficiency. If cobalamin deficiency is suspected, e.g. in pregnant women on vegan diet, urinary methylmalonic acid excretion and plasma homocysteine levels should be determined and cobalamin substitution should be started at an early stage to avoid potentially irreversible damage of the fetus.",
"title": "[Floppy baby with macrocytic anemia and vegan mother]."
},
{
"docid": "MED-3706",
"text": "Autoimmune diseases are complex diseases resulting of the interaction between both genetics and environmental factors over time. Different phases in the development of autoimmune diseases are characterized by the detection of serum autoantibodies several months or years before the onset of clinical manifestations and subsequent diagnosis. In addition to serum antibodies, genetic susceptibility factors may predict the future development of the disease. Currently, prediction in type 1 diabetes is the most accurate, with the analysis of genetic susceptibility factors in first-degree relatives of patients and several autoantibody tests. In the future, multiple antibodies test, in combination with the analysis of genetics, epigenetics and immunological anomalies in fine models may allow the precise prediction in autoimmune diseases. Prevention measures might thus be introduced as an attempt to avoid or delay the disease. Copyright © 2011 Elsevier B.V. All rights reserved.",
"title": "Are autoimmune diseases predictable?"
},
{
"docid": "MED-1125",
"text": "Genetic, molecular and biological studies indicate that rheumatoid arthritis (RA), a severe arthritic disorder affecting approximately 1% of the population in developed countries, is caused by an upper urinary tract infection by the microbe, Proteus mirabilis. Elevated levels of specific antibodies against Proteus bacteria have been reported from 16 different countries. The pathogenetic mechanism involves six stages triggered by cross-reactive autoantibodies evoked by Proteus infection. The causative amino acid sequences of Proteus namely, ESRRAL and IRRET, contain arginine doublets which can be acted upon by peptidyl arginine deiminase thereby explaining the early appearance of anti-citrullinated protein antibodies in patients with RA. Consequently, RA patients should be treated early with anti-Proteus antibiotics as well as biological agents to avoid irreversible joint damages. © 2013 APMIS. Published by John Wiley & Sons Ltd.",
"title": "Rheumatoid arthritis is caused by a Proteus urinary tract infection."
},
{
"docid": "MED-1667",
"text": "Non-specific low back pain has become a major public health problem worldwide. The lifetime prevalence of low back pain is reported to be as high as 84%, and the prevalence of chronic low back pain is about 23%, with 11-12% of the population being disabled by low back pain. Mechanical factors, such as lifting and carrying, probably do not have a major pathogenic role, but genetic constitution is important. History taking and clinical examination are included in most diagnostic guidelines, but the use of clinical imaging for diagnosis should be restricted. The mechanism of action of many treatments is unclear, and effect sizes of most treatments are low. Both patient preferences and clinical evidence should be taken into account for pain management, but generally self-management, with appropriate support, is recommended and surgery and overtreatment should be avoided. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Non-specific low back pain."
},
{
"docid": "MED-3385",
"text": "Diacetyl-containing butter flavor was identified as the cause of an outbreak of bronchiolitis obliterans (BO) and other lung diseases in popcorn-plant workers. Litigation documents show that the outbreak was both predictable and preventable. The industry trade organization was aware of BO cases in workers at butter-flavoring and popcorn-manufacturing plants but often failed to implement industrial hygiene improvements and actively hid pertinent warning information. Due to weaknesses in the organization and mandates of regulatory bodies, organizations such as NIOSH, OSHA, the FDA, particularly the \"generally recognized as safe\" (GRAS) system, and the EPA failed to detect and prevent the outbreak, which highlights the need for systemic changes in food-product regulation, including the need for corporations to act responsibly, for stronger regulations with active enforcement, for a restructuring of the GRAS system, and for criminal penalties against corporations and professionals who knowingly hide information relevant to worker protection.",
"title": "Popcorn-worker lung caused by corporate and regulatory negligence: an avoidable tragedy."
},
{
"docid": "MED-3760",
"text": "The authors sent a questionnaire to 772 randomly selected Danish clinicians and asked them about their use of placebo interventions. Sixty-five percent responded. Among the general practitioners, 86% (95% confidence interval 81-91) reported to have used placebo interventions at least once, and 48% (41-55) to have used placebo interventions more than ten times, within the last year. Hospital-based doctors and private specialists reported to have used placebo interventions less frequently (p < .001). The most important reason for the use of placebo interventions was to avoid a confrontation with the patient. Typical placebos were antibiotics for viral infections. Approximately 30% (28-36) of the clinicians believed in an effect of placebo interventions on objective outcomes, and 46% (42-50) found clinical placebo interventions generally ethically acceptable.",
"title": "The use of placebo interventions in medical practice--a national questionnaire survey of Danish clinicians."
},
{
"docid": "MED-4391",
"text": "Cancer is a leading cause of death worldwide. There are a lot of cancer causing agents which are divided as physical carcinogens, chemical carcinogens and biological carcinogens. But most of the carcinogens or causes of cancer are related to our lifestyle like diet, habit, occupation, radiation and some infection, etc. Chemoprevention is highly necessary to prevent cancer related preterm death. For this besides avoiding the causes of cancer we should concentrate ourselves on our diet. Because, numerous phytochemicals derived from edible plants have been reported to interfere with a specific stage of the carcinogenic process. Many mechanisms have been shown to account for the anticarcinogenic actions of dietary constituents and recently attention has been focused on intracellular-signalling cascades as common molecular targets for various chemopreventive phytochemicals. In this study, we tried to describe lifestyle related causes of cancer and the molecular basis of cancer prevention through the phytochemicals.",
"title": "Lifestyle related causes of cancer and chemoprevention through phytonutrients."
},
{
"docid": "MED-1586",
"text": "Women with a multiple pregnancy face greater risks for themselves and their infants than women pregnant with one child. Pre-pregnancy care should focus on avoiding multiple pregnancy. Early prenatal care centres on determining chorionicity and screening for fetal anomalies, with later care focusing on the presentation, prediction and management of preterm birth, and intrauterine growth restriction. The optimal timing and mode of birth are the focus of current multicentre, randomised, controlled trials. However, the data from such trials on care for women with a multiple pregnancy are limited. Many areas of care require better-quality information, including when using assisted reproductive techniques, the optimal number of embryos to be transferred, care after the diagnosis of chorionicity, and the benefits of specialised multiple pregnancy clinics. Better-quality information is required to inform clinical practice for women with complications of multiple pregnancy, including monoamniotic twin pregnancy, treatment of twin-to-twin transfusion syndrome, and care following single intrauterine fetal death.",
"title": "Evidence-based care of women with a multiple pregnancy."
}
] |
1058
|
Roughly 55% of women with chronic pelvic pain have no underlying pathology.
|
[
{
"docid": "13027590",
"text": "CONTEXT Chronic pelvic pain is a common condition with a major effect on health-related quality of life, work productivity, and health care use. Operative interruption of nerve trunks in the uterosacral ligaments by laparoscopic uterosacral nerve ablation (LUNA) is a treatment option for patients with chronic pelvic pain. OBJECTIVE To assess the effectiveness of LUNA in patients with chronic pelvic pain. DESIGN, SETTING, AND PARTICIPANTS Randomized controlled trial of 487 women with chronic pelvic pain lasting longer than 6 months without or with minimal endometriosis, adhesions, or pelvic inflammatory disease, who were recruited to the study by consultant gynecological surgeons from 18 UK hospitals between February 1998 and December 2005. Follow-up was conducted by questionnaires mailed at 3 and 6 months and at 1, 2, 3, and 5 years. INTERVENTION Bilateral LUNA or laparoscopy without pelvic denervation (no LUNA); participants were blinded to the treatment allocation. MAIN OUTCOME MEASURES The primary outcome was pain, which was assessed by a visual analogue scale. Data concerning the 3 types of pain (noncyclical pain, dysmenorrhea, and dyspareunia) were analyzed separately as was the worst pain level experienced from any of these 3 types of pain. The secondary outcome was health-related quality of life, which was measured using a generic instrument (EuroQoL EQ-5D and EQ-VAS). RESULTS After a median follow-up of 69 months, there were no significant differences reported on the visual analogue pain scales for the worst pain (mean difference between the LUNA group and the no LUNA group, -0.04 cm [95% confidence interval {CI}, -0.33 to 0.25 cm]; P = .80), noncyclical pain (-0.11 cm [95% CI, -0.50 to 0.29 cm]; P = .60), dysmenorrhea (-0.09 cm [95% CI, -0.49 to 0.30 cm]; P = .60), or dyspareunia (0.18 cm [95% CI, -0.22 to 0.62 cm]; P = .40). No differences were observed between the LUNA group and the no LUNA group for quality of life. CONCLUSION Among women with chronic pelvic pain, LUNA did not result in improvements in pain, dysmenorrhea, dyspareunia, or quality of life compared with laparoscopy without pelvic denervation. TRIAL REGISTRATION controlled-trials.com Identifier: ISRCTN41196151.",
"title": "Laparoscopic uterosacral nerve ablation for alleviating chronic pelvic pain: a randomized controlled trial."
}
] |
[
{
"docid": "32462603",
"text": "OBJECTIVE To determine the incidence of surgically managed pelvic organ prolapse and urinary incontinence in a population-based cohort, and to describe their clinical characteristics. METHODS Our retrospective cohort study included all patients undergoing surgical treatment for prolapse and incontinence during 1995; all were members of Kaiser Permanente Northwest, which included 149,554 women age 20 or older. A standardized data-collection form was used to review all inpatient and outpatient charts of the 395 women identified. Variables examined included age, ethnicity, height, weight, vaginal parity, smoking history, medical history, and surgical history, including the preoperative evaluation, procedure performed, and details of all prior procedures. Analysis included calculation of age-specific and cumulative incidences and determination of the number of primary operations compared with repeat operations performed for prolapse or incontinence. RESULTS The age-specific incidence increased with advancing age. The lifetime risk of undergoing a single operation for prolapse or incontinence by age 80 was 11.1%. Most patients were older, postmenopausal, parous, and overweight. Nearly half were current or former smokers and one-fifth had chronic lung disease. Reoperation was common (29.2% of cases), and the time intervals between repeat procedures decreased with each successive repair. CONCLUSION Pelvic floor dysfunction is a major health issue for older women, as shown by the 11.1% lifetime risk of undergoing a single operation for pelvic organ prolapse and urinary incontinence, as well as the large proportion of reoperations. Our results warrant further epidemiologic research in order to determine the etiology, natural history, and long-term treatment outcomes of these conditions.",
"title": "Epidemiology of surgically managed pelvic organ prolapse and urinary incontinence."
},
{
"docid": "12561083",
"text": "BACKGROUND Several studies have demonstrated that women with nonobstructive coronary disease have a high rate of subsequent investigations, rehospitalizations for recurrent chest pain, and repeat coronary angiography. The sex specificity of this finding is unclear. We therefore undertook an evaluation of sex differences in rehospitalization for acute coronary syndrome (ACS) or chest pain in patients with \"angiographically normal\" coronaries. METHODS A retrospective cohort study using prospectively collected angiographic and clinical data on all patients in British Columbia, Canada, presenting for their first cardiac catheterization with suspected ischemic heart disease but angiographically normal coronaries. RESULTS Among 32,856 patients, 7.1% of men versus 23.3% of women were angiographically normal (P < .001). Among angiographically normal patients, women were older and more likely to present with hypertension, prior stroke, chronic obstructive pulmonary disease, and peripheral vascular disease than men, but Canadian Cardiovascular Society class of angina did not vary by sex. Within 1 year, 1.0% died, (19 women, 18 men, P = .27) and 0.6% had a stroke (13 women, 9 men, P = .91). Readmission to hospital for ACS or chest pain requiring catheterization was significantly higher in women compared to men (adjusted OR 4.06; 95% CI 1.15-14.31). CONCLUSIONS In a contemporary, population-based cohort presenting for cardiac catheterization for suspected ischemia, women with angiographically normal coronaries were >4 times more likely to be readmitted to hospital for ACS/chest pain within 180 days compared to men. The observed sex difference has important social and economic implications and suggests that traditional diagnostic methods may not be optimal for women.",
"title": "Angina with \"normal\" coronary arteries: sex differences in outcomes."
},
{
"docid": "32534305",
"text": "OBJECTIVE Hyperinsulinemia may promote mammary carcinogenesis. Insulin resistance has been linked to an increased risk of breast cancer and is also characteristic of type 2 diabetes. We prospectively evaluated the association between type 2 diabetes and invasive breast cancer incidence in the Nurses' Health Study. RESEARCH DESIGN AND METHODS A total of 116,488 female nurses who were 30-55 years old and free of cancer in 1976 were followed through 1996 for the occurrence of type 2 diabetes and through 1998 for incident invasive breast cancer, verified by medical records and pathology reports. RESULTS During 2.3 million person-years of follow-up, we identified 6,220 women with type 2 diabetes and 5,189 incident cases of invasive breast cancer. Women with type 2 diabetes had a modestly elevated incidence of breast cancer (hazard ratio [HR] = 1.17; 95% CI 1.01-1.35) compared with women without diabetes, independent of age, obesity, family history of breast cancer, history of benign breast disease, reproductive factors, physical activity, and alcohol consumption. This association was apparent among postmenopausal women (1.16; 0.98-1.62) but not premenopausal women (0.83; 0.48-1.42). The association was predominant among women with estrogen receptor-positive breast cancer (1.22; 1.01-1.47). CONCLUSIONS Women with type 2 diabetes may have a slightly increased risk of breast cancer.",
"title": "Type 2 diabetes and subsequent incidence of breast cancer in the Nurses' Health Study."
},
{
"docid": "42185082",
"text": "Factors associated with primary care utilization and health insurance coverage were examined among 511 women leaving jail in New York City from 1997-2001. One year after release, roughly half of the sample reported primary care utilization (47%) and health insurance coverage (56%). Neither outcome was more likely among those reporting diabetes, asthma, or depression. Primary care utilization was more likely among those reporting receipt of public benefits, health insurance coverage, moderate social support, avoidance of illegal activity, and HIV seropositivity. Health insurance coverage was associated with receipt of public benefits, hospitalization, primary care, and avoiding re-arrest. This study demonstrated that a majority of women leaving jail, including those with chronic diseases, lack primary care. These data highlight the need to plan for continuity of care from corrections to the community and suggest further that this can be facilitated with provision of health benefits and social support.",
"title": "Primary care and health insurance among women released from New York City jails."
},
{
"docid": "27711043",
"text": "OBJECTIVES To describe the impact of musculoskeletal pain (MP); to compare management of MP by the population and by primary care physicians; and to identify misconceptions about treatment. METHODS 5803 people with MP and 1483 primary care physicians, randomly selected, in eight European countries were interviewed by telephone. A structured questionnaire was used to ask about usual management of MP and perceived benefits and risks of treatment. Current health status (SF-12) was also assessed. RESULTS From primary care physicians' perceptions, MP appears to be well managed. All presenting patients are offered some form of treatment, 90% or more doctors are trying to improve patients' quality of life, and most are aware and concerned about the risks of treatment with NSAIDs. From a population perspective, up to 27% of people with pain do not seek medical help and of those who do, several wait months/years before seeing a doctor. 55% or fewer patients who have seen a doctor are currently receiving prescription treatment for their pain. Communication between doctors and patients is poor; few patients are given information about their condition; and many have misconceptions about treatment. CONCLUSIONS Management of MP is similar across eight European countries, but there is discordance between physician and patient perspectives of care. Some people with pain have never sought medical help despite being in constant/daily pain. Those who do seek help receive little written information or explanation and many have misperceptions about the benefits and risks of treatment that limit their ability to actively participate in decisions about their care.",
"title": "Musculoskeletal pain in Europe: its impact and a comparison of population and medical perceptions of treatment in eight European countries."
},
{
"docid": "6191684",
"text": "CONTEXT Chronic tension-type headaches are characterized by near-daily headaches and often are difficult to manage in primary practice. Behavioral and pharmacological therapies each appear modestly effective, but data are lacking on their separate and combined effects. OBJECTIVE To evaluate the clinical efficacy of behavioral and pharmacological therapies, singly and combined, for chronic tension-type headaches. DESIGN AND SETTING Randomized placebo-controlled trial conducted from August 1995 to January 1998 at 2 outpatient sites in Ohio. PARTICIPANTS Two hundred three adults (mean age, 37 years; 76% women) with diagnosis of chronic tension-type headaches (mean, 26 headache d/mo). INTERVENTIONS Participants were randomly assigned to receive tricyclic antidepressant (amitriptyline hydrochloride, up to 100 mg/d, or nortriptyline hydrochloride, up to 75 mg/d) medication (n = 53), placebo (n = 48), stress management (eg, relaxation, cognitive coping) therapy (3 sessions and 2 telephone contacts) plus placebo (n = 49), or stress management therapy plus antidepressant medication (n = 53). MAIN OUTCOME MEASURES Monthly headache index scores calculated as the mean of pain ratings (0-10 scale) recorded by participants in a daily diary 4 times per day; number of days per month with at least moderate pain (pain rating >/=5), analgesic medication use, and Headache Disability Inventory scores, compared by intervention group. RESULTS Tricyclic antidepressant medication and stress management therapy each produced larger reductions in headache activity, analgesic medication use, and headache-related disability than placebo, but antidepressant medication yielded more rapid improvements in headache activity. Combined therapy was more likely to produce clinically significant (>/=50%) reductions in headache index scores (64% of participants) than antidepressant medication (38% of participants; P =.006), stress management therapy (35%; P =.003), or placebo (29%; P =.001). On other measures the combined therapy and its 2 component therapies produced similar outcomes. CONCLUSIONS Our results indicate that antidepressant medication and stress management therapy are each modestly effective in treating chronic tension-type headaches. Combined therapy may improve outcome relative to monotherapy.",
"title": "Management of chronic tension-type headache with tricyclic antidepressant medication, stress management therapy, and their combination: a randomized controlled trial."
},
{
"docid": "36721932",
"text": "OBJECTIVE Nociceptive and neuropathic components both contribute to pain. Since these components require different pain management strategies, correct pain diagnosis before and during treatment is highly desirable. As low back pain (LBP) patients constitute an important subgroup of chronic pain patients, we addressed the following issues: (i) to establish a simple, validated screening tool to detect neuropathic pain (NeP) components in chronic LBP patients, (ii) to determine the prevalence of neuropathic pain components in LBP in a large-scale survey, and (iii) to determine whether LBP patients with an NeP component suffer from worse, or different, co-morbidities. METHODS In co-operation with the German Research Network on Neuropathic Pain we developed and validated the painDETECT questionnaire (PD-Q) in a prospective, multicentre study and subsequently applied it to approximately 8000 LBP patients. RESULTS The PD-Q is a reliable screening tool with high sensitivity, specificity and positive predictive accuracy; these were 84% in a palm-top computerised version and 85%, 80% and 83%, respectively, in a corresponding pencil-and-paper questionnaire. In an unselected cohort of chronic LBP patients, 37% were found to have predominantly neuropathic pain. Patients with NeP showed higher ratings of pain intensity, with more (and more severe) co-morbidities such as depression, panic/anxiety and sleep disorders. This also affected functionality and use of health-care resources. On the basis of given prevalence of LBP in the general population, we calculated that 14.5% of all female and 11.4% of all male Germans suffer from LBP with a predominant neuropathic pain component. CONCLUSION Simple, patient-based, easy-to-use screening questionnaires can determine the prevalence of neuropathic pain components both in individual LBP patients and in heterogeneous cohorts of such patients. Since NeP correlates with more intense pain, more severe co-morbidity and poorer quality of life, accurate diagnosis is a milestone in choosing appropriate therapy.",
"title": "painDETECT: a new screening questionnaire to identify neuropathic components in patients with back pain."
},
{
"docid": "21274919",
"text": "OBJECTIVE Chronic physical comorbidity is common in dementia. However, there is an absence of evidence to support good practice guidelines for attention to these problems. We aimed to study the extent of this comorbidity and its impact on cognitive function and disability in population-based studies in low and middle income countries, where chronic diseases and impairments are likely to be both common and undertreated. METHODS A multicentre cross-sectional survey of all over 65 year old residents (n = 15 022) in 11 catchment areas in China, India, Cuba, Dominican Republic, Venezuela, Mexico and Peru. We estimated the prevalence of pain, incontinence, hearing and visual impairments, mobility impairment and undernutrition according to the presence of dementia and its severity, and, among those with dementia, the independent contribution of these impairments to cognitive function and disability, adjusting for age, gender, education and dementia severity. RESULTS Incontinence, hearing impairment, mobility impairment and undernutrition were consistently linearly associated with the presence of dementia and its severity across regions. Among people with dementia, incontinence, hearing impairment and mobility impairment were independently associated with disability in all regions while the contributions of pain, visual impairment and undernutrition were inconsistent. Only hearing impairment made a notable independent contribution to cognitive impairment. CONCLUSIONS There is an urgent need for clinical trials of the feasibility, efficacy and cost-effectiveness of regular physical health checks and remediation of identified pathologies, given the considerable comorbidity identified in our population based studies, and the strong evidence for independent impact upon functioning.",
"title": "The association between common physical impairments and dementia in low and middle income countries, and, among people with dementia, their association with cognitive function and disability. A 10/66 Dementia Research Group population-based study."
},
{
"docid": "22236223",
"text": "Pregnancy in women with different renal diseases has important consequences for the developing fetus and maternal health. Kidneys and the urinary tract have to adapt to the pregnancy status and therefore suffer significant anatomical, hemodynamic and endocrine changes. Failure to adapt can aggravate the preexisting maternal disease and can also create suboptimal environment for fetal development and increase the risk of obstetric complications. Knowledge and correct interpretation of the renal functional tests is necessary for the modern obstetrician, avoiding an incorrect diagnosis for renal disease where only specific renal changes during pregnancy are present, but meanwhile a correct evaluation of the renal function and changes can detect a pathology that can aggravate both the mother’s and the baby’s condition. Improvement and better understanding of the renal pathophysiology in pregnancy made possible that pregnant woman look forward for a good outcome, including here also the women with renal transplant. Nowadays is underlined the concept of multidisciplinary teamwork, a very important concept of modern medicine. The obstetrician should consider nephrologists as key players in the team and in our opinion should refer to them the pregnant women for a routine check-up of the renal status in the 2nd or beginning of 3rd trimester by ultrasound, beside the usual blood and urine analysis. The nephrologists and urologists should be involved in the management of severe medical conditions, such as preeclampsia, acute and chronic renal failure and never the less in the complex management of dialysis or renal transplant patients. In pregnancy it can be encountered several renal diseases, some of them preexisting the pregnancy and other developed or being direct influenced by pregnancy. This chapter will discuss briefly the basic evaluation of renal status in order to present and better understand the acute and chronic renal disorders in pregnancy. The chapter will focus on the most common preexisting diseases in pregnancy such as: chronic glomerulonephritis, secondary glomerular nephropathies, interstitial nephropathies (chronic pyelonephritis, renal tuberculosis), diabetes nephropathy, unique surgical kidney, chronic renal failure. From the renal diseases directly influenced by pregnancy it will be discussed: asymptomatic bacteriuria, symptomatic urinary infection, urolithiasis and acute renal failure in pregnancy. It will be presented also the management of dialysis in pregnancy and pregnant women with renal transplant.",
"title": "Renal Disease and Pregnancy"
},
{
"docid": "8570317",
"text": "We conducted a two-stage population-based headache survey among subjects aged > or = 15 in Taipei, Taiwan. Subjects with chronic daily headache (CDH) in the past year were identified, interviewed and followed-up. CDH was defined as a headache frequency > 15 days/month, with a duration > 4 h/day. Of the 3377 participants, 108 (3.2%) fulfilled the criteria for CDH, with a higher prevalence in women (4.3%) than men (1.9%). TM was the most common subtype (55%), followed by CTTH (44%). Thirty-four per cent of the CDH subjects overused analgesics. At the 2-year follow-up, 35% of the CDH subjects still had CDH. The significant predictors for persistent CDH at follow-up included: older age ( > or = 40 years) (RR = 2.4), CDH onset after 32 years (RR = 1.8), CDH duration > or = 6 years (RR = 2.0), medication overuse (RR = 1.8), and \"daily\" headache (RR = 2.1). We found that CDH is not uncommon in the community and its prevalence is similar among different populations. Older subjects and those with medication overuse may have a more protracted course of illness.",
"title": "Chronic daily headache in Taipei, Taiwan: prevalence, follow-up and outcome predictors."
},
{
"docid": "3190689",
"text": "BACKGROUND Laparoscopic adhesiolysis for chronic abdominal pain is controversial and is not evidence based. We aimed to test our hypothesis that laparoscopic adhesiolysis leads to substantial pain relief and improvement in quality of life in patients with adhesions and chronic abdominal pain. METHODS Patients had diagnostic laparoscopy for chronic abdominal pain attributed to adhesions; other causes for their pain had been excluded. If adhesions were confirmed during diagnostic laparoscopy, patients were randomly assigned either to laparoscopic adhesiolysis or no treatment. Treatment allocation was concealed from patients, and assessors were unaware of patients' treatment and outcome. Pain was assessed for 1 year by visual analogue score (VAS) score (scale 0-100), pain change score, use of analgesics, and quality of life score. Analysis was by intention to treat. FINDINGS Of 116 patients enrolled for diagnostic laparoscopy, 100 were randomly allocated either laparoscopic adhesiolysis (52) or no treatment (48). Both groups reported substantial pain relief and a significantly improved quality of life, but there was no difference between the groups (mean change from baseline of VAS score at 12 months: difference 3 points, p=0.53; 95% CI -7 to 13). INTERPRETATION Although laparoscopic adhesiolysis relieves chronic abdominal pain, it is not more beneficial than diagnostic laparoscopy alone. Therefore, laparoscopic adhesiolysis cannot be recommended as a treatment for adhesions in patients with chronic abdominal pain.",
"title": "Laparoscopic adhesiolysis in patients with chronic abdominal pain: a blinded randomised controlled multi-centre trial."
},
{
"docid": "29253460",
"text": "OBJECTIVE To assess whether sex differences exist in the angiographic severity, management and outcomes of acute coronary syndromes (ACS). METHODS The study comprised 7638 women and 19 117 men with ACS who underwent coronary angiography and were included in GRACE (Global Registry of Acute Coronary Events) from 1999-2006. Normal vessels/mild disease was defined as <50% stenosis in all epicardial vessels; advanced disease was defined as >or=one vessel with >or=50% stenosis. RESULTS Women were older than men and had higher rates of cardiovascular risk factors. Men and women presented equally with chest pain; however, jaw pain and nausea were more frequent among women. Women were more likely to have normal/mild disease (12% vs 6%, p<0.001) and less likely to have left-main and three-vessel disease (27% vs 32%, p<0.001) or undergo percutaneous coronary intervention (65% vs 68%, p<0.001). Women and men with normal and mild disease were treated less aggressively than those with advanced disease. Women with advanced disease had a higher risk of death (4% vs 3%, p<0.01). After adjustment for age and extent of disease, women were more likely to have adverse outcomes (death, myocardial infarction, stroke and rehospitalisation) at six months compared to men (odds ratio 1.24, 95% confidence interval 1.14 to 1.34); however, sex differences in mortality were no longer statistically significant. CONCLUSIONS Women with ACS were more likely to have cardiovascular disease risk factors and atypical symptoms such as nausea compared with men, but were more likely to have normal/mild angiographic coronary artery disease. Further study regarding sex differences related to disease severity is warranted.",
"title": "Sex-related differences in the presentation, treatment and outcomes among patients with acute coronary syndromes: the Global Registry of Acute Coronary Events."
},
{
"docid": "13223957",
"text": "OBJECTIVE The cardinal indication for surgical treatment of gallstones is pain attacks. However, following cholecystectomy, 20% of patients remain symptomatic. It is unclear to what extent post-cholecystectomy symptoms can be ascribed to persistence of preoperative symptoms or to new pathology. The pain and digestive pattern in gallstone patients has not been defined in a recent setting with ultrasonography as the diagnostic method. The aim of this study was to characterize a pain pattern that is typical for gallstone disease and to describe the extent of associated dyspepsia. MATERIAL AND METHODS A total of 220 patients with symptomatic gallstone disease including complicated disease (acute cholecystitis and common bile duct stones) were interviewed using detailed questionnaires to disclose pain patterns and symptoms of indigestion. RESULTS All patients had pain in the right upper quadrant (RUQ) including the upper midline epigastrium. The pain was localized to the right subcostal area in 20% and to the upper epigastrium in 14%, and in the rest (66%) it was more evenly distributed. An area of maximal pain could be defined in 90%. Maximal pain was located under the costal arch in 51% of patients and in the epigastrium in 41%, but in 3% behind the sternum and in 5% in the back. The pain was referred to the back in 63% of the patients. The mean visual analogue scale (VAS) score was very high: 90 mm on a 0-100 scale. A pattern of incipient or low-grade warning pain with a subsequent relatively steady state until subsiding in the same fashion was present in 90% of the patients. An urge to walk around was experienced by 71%. Pain attacks usually occurred in the late evening or at night (77%), with 85% of the attacks lasting for more than one hour and almost never less than half an hour. Sixty-six percent of the patients were intolerant to at least one kind of food, but only 48% to fatty foods. Symptoms of functional indigestion (gastroesophageal reflux, dyspepsia or irritable bowel symptoms) were seen in the vast majority in association with attacks. CONCLUSIONS Gallstone-associated pain follows a certain pattern in the majority of patients. The pain is located in a defined area with a point of maximum intensity, is usually referred, and occurs mainly at night with duration of more than one hour. The majority of patients experience functional indigestion, mainly of the reflux type or dyspepsia.",
"title": "Pain attacks in non-complicated and complicated gallstone disease have a characteristic pattern and are accompanied by dyspepsia in most patients: the results of a prospective study."
},
{
"docid": "14724693",
"text": "CONTEXT Chronic low back pain (LBP) with degenerative lumbar osteoarthritis (OA) is widespread in the adult population. Although glucosamine is increasingly used by patients with chronic LBP, little is known about its effect in this setting. OBJECTIVE To investigate the effect of glucosamine in patients with chronic LBP and degenerative lumbar OA. DESIGN, SETTING, AND PARTICIPANTS A double-blind, randomized, placebo-controlled trial conducted at Oslo University Hospital Outpatient Clinic, Oslo, Norway, with 250 patients older than 25 years of age with chronic LBP (>6 months) and degenerative lumbar OA. INTERVENTIONS Daily intake of 1500 mg of oral glucosamine (n = 125) or placebo (n = 125) for 6 months, with assessment of effect after the 6-month intervention period and at 1 year (6 months postintervention). MAIN OUTCOME MEASURES The primary outcome was pain-related disability measured with the Roland Morris Disability Questionnaire (RMDQ). Secondary outcomes were numerical scores from pain-rating scales of patients at rest and during activity, and the quality-of-life EuroQol-5 Dimensions (EQ-5D) instrument. Data collection occurred during the intervention period at baseline, 6 weeks, 3 and 6 months, and again 6 months following the intervention at 1 year. Group differences were analyzed using linear mixed models analysis. RESULTS At baseline, mean RMDQ scores were 9.2 (95% confidence interval [CI], 8.4-10.0) for glucosamine and 9.7 (95% CI, 8.9-10.5) for the placebo group (P = .37). At 6 months, the mean RMDQ score was the same for the glucosamine and placebo groups (5.0; 95% CI, 4.2-5.8). At 1 year, the mean RMDQ scores were 4.8 (95% CI, 3.9-5.6) for glucosamine and 5.5 (95% CI, 4.7-6.4) for the placebo group. No statistically significant difference in change between groups was found when assessed after the 6-month intervention period and at 1 year: RMDQ (P = .72), LBP at rest (P = .91), LBP during activity (P = .97), and quality-of-life EQ-5D (P = .20). Mild adverse events were reported in 40 patients in the glucosamine group and 46 in the placebo group (P = .48). CONCLUSIONS Among patients with chronic LBP and degenerative lumbar OA, 6-month treatment with oral glucosamine compared with placebo did not result in reduced pain-related disability after the 6-month intervention and after 1-year follow-up. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00404079.",
"title": "Effect of glucosamine on pain-related disability in patients with chronic low back pain and degenerative lumbar osteoarthritis: a randomized controlled trial."
},
{
"docid": "22707413",
"text": "This article describes the development and validation of the S-LANSS score, a self-report version of the Leeds Assessment of Neuropathic Symptoms and Signs pain scale. The S-LANSS aims to identify pain of predominantly neuropathic origin, as distinct from nociceptive pain, without the need for clinical examination. Two hundred patients with chronic pain were asked to complete the S-LANSS unaided. A researcher then administered the S-LANSS scale and the Neuropathic Pain Scale (NPS) in interview format. An independent clinician determined the pain type (neuropathic versus nociceptive) and rated his or her certainty about diagnosis. The S-LANSS scale was also incorporated into a chronic pain questionnaire that was sent to 160 community patients and 150 newly referred patients waiting for pain clinic assessment. The S-LANSS scale correctly identified 75% of pain types when self-completed and 80% when used in interview format. Sensitivity for self-completed S-LANSS scores ranged from 74% to 78%, depending on the cutoff score. There were significant associations between NPS items and total score with S-LANSS score. In the postal survey, completed questionnaires were returned by 57% of patients (n = 174). Internal consistency and convergent validity of the survey S-LANSS scores were confirmed. The findings support the S-LANSS scale as a valid and reliable self-report instrument for identifying neuropathic pain and it is also acceptable for use in postal survey research. Establishing valid measures of symptoms and signs in neuropathic pain will allow standardized comparisons with other investigational measures. This might lead to new insights into the relationship between pathophysiologic mechanisms and clinical manifestations of pain.",
"title": "The S-LANSS score for identifying pain of predominantly neuropathic origin: validation for use in clinical and postal research."
},
{
"docid": "21957231",
"text": "The aim of the present study was to examine the association between pain catastrophizing and general health status in a Dutch adult community sample, including various subgroups of people with musculoskeletal pain in the analyses. For exploratory reasons this study partly replicated previous studies of the factor structure, reliability, and validity of the Pain Catastrophizing Scale (PCS). Results demonstrated that across different pain subgroups, catastrophizing uniquely contributed variance to the prediction of the various aspects of general health status beyond the variance explained by pain intensity, age, gender, and chronicity. Across subgroups strongest associations were found between catastrophizing and mental health, general health perception, social functioning, and vitality. Furthermore, the association between catastrophizing and the various aspects of general health status was not moderated by the chronicity of the pain. Results of the confirmatory factor analysis statistically confirmed a three-factor model of the PCS, which was invariant across different subgroups of people with musculoskeletal pain. Inter-factor correlations were high, and the incremental explanatory power of the three-factor model over that of a one-factor model was only marginal. This implies that a one-factor model might be justifiable as well, at least in the general community. Across various pain subgroups the reliability of the PCS total and subscales was adequate. Additional evidence for the concurrent validity of the PCS was found as well.",
"title": "Pain catastrophizing and general health status in a large Dutch community sample."
},
{
"docid": "44586415",
"text": "QUESTION Do clinical tests accurately diagnose rotator cuff pathology? DESIGN A systematic review of investigations into the diagnostic accuracy of clinical tests for rotator cuff pathology. PARTICIPANTS People with shoulder pain who underwent clinical testing in order to diagnose rotator cuff pathology. OUTCOME MEASURES The diagnostic accuracy of clinical tests was determined using likelihood ratios. RESULTS Thirteen studies met the inclusion criteria. The 13 studies evaluated 14 clinical tests in 89 separate evaluations of diagnostic accuracy. Only one evaluation, palpation for supraspinatus ruptures, resulted in significant positive and negative likelihood ratios. Eight of the 89 evaluations resulted in either significant positive or negative likelihood ratios. However, none of these eight positive or negative likelihood ratios were found in other studies. Of the 89 evaluations of clinical tests 71 (80%) did not result in either significant positive or negative likelihood ratio evaluations across different studies. CONCLUSION Overall, most tests for rotator cuff pathology were inaccurate and cannot be recommended for clinical use. At best, suspicion of a rotator cuff tear may be heightened by a positive palpation, combined Hawkins/painful arc/infraspinatus test, Napoleon test, lift-off test, belly-press test, or drop-arm test, and it may be reduced by a negative palpation, empty can test or Hawkins-Kennedy test.",
"title": "Most clinical tests cannot accurately diagnose rotator cuff pathology: a systematic review."
},
{
"docid": "19529370",
"text": "Although skeletal pain can have a marked impact on a patient's functional status and quality of life, relatively little is known about the specific populations of peripheral nerve fibers that drive non-malignant bone pain. In the present report, neonatal male Sprague-Dawley rats were treated with capsaicin or vehicle and femoral fracture was produced when the animals were young adults (15-16 weeks old). Capsaicin treatment, but not vehicle, resulted in a significant (>70%) depletion in the density of calcitonin-gene related peptide positive (CGRP(+)) sensory nerve fibers, but not 200 kDa neurofilament H positive (NF200(+)) sensory nerve fibers in the periosteum. The periosteum is a thin, cellular and fibrous tissue that tightly adheres to the outer surface of all but the articulated surface of bone and appears to play a pivotal role in driving fracture pain. In animals treated with capsaicin, but not vehicle, there was a 50% reduction in the severity, but no change in the time course, of fracture-induced skeletal pain-related behaviors as measured by spontaneous flinching, guarding and weight bearing. These results suggest that both capsaicin-sensitive (primarily CGRP(+) C-fibers) and capsaicin-insensitive (primarily NF200(+) A-delta fibers) sensory nerve fibers participate in driving skeletal fracture pain. Skeletal pain can be a significant impediment to functional recovery following trauma-induced fracture, osteoporosis-induced fracture and orthopedic surgery procedures such as knee and hip replacement. Understanding the specific populations of sensory nerve fibers that need to be targeted to inhibit the generation and maintenance of skeletal pain may allow the development of more specific mechanism-based therapies that can effectively attenuate acute and chronic skeletal pain.",
"title": "Capsaicin-sensitive sensory nerve fibers contribute to the generation and maintenance of skeletal fracture pain."
},
{
"docid": "58564850",
"text": "Background We aimed to determine the prevalence and gap in use of mental health services for late-life depression in four European regions (Western Europe, Scandinavia, Southern Europe and Central and Eastern Europe) and explore socio-demographic, social and health-related factors associated with it. Methods We conducted a cross-sectional study based on data from the Survey on Health, Ageing and Retirement in Europe. Participants were a population-based sample of 28 796 persons (53% women, mean age 74 years old) residing in Europe. Mental health service use was estimated using information about the diagnosis or treatment for depression. Results The prevalence of late-life depression was 29% in the whole sample and was highest in Southern Europe (35%), followed by Central and Eastern Europe (32%), Western Europe (26%) and lowest in Scandinavia (17%). Factors that had the strongest association with depression were total number of chronic diseases, pain, limitations in instrumental activities of daily living, grip strength and cognitive impairment. The gap in mental health service use was 79%. Conclusions We suggest that interventions to decrease the burden of late-life depression should be targeted at individuals that are affected by chronic somatic comorbidities and are limited in mental and physical functioning. Promotion of help-seeking of older adults, de-stigmatization of mental illness and education of general practitioners could help decrease the gap in mental health service utilization.",
"title": "Prevalence of late-life depression and gap in mental health service use across European regions."
},
{
"docid": "11254556",
"text": "Synaptic long-term potentiation (LTP) at spinal neurons directly communicating pain-specific inputs from the periphery to the brain has been proposed to serve as a trigger for pain hypersensitivity in pathological states. Previous studies have functionally implicated the NMDA receptor-NO pathway and the downstream second messenger, cGMP, in these processes. Because cGMP can broadly influence diverse ion-channels, kinases, and phosphodiesterases, pre- as well as post-synaptically, the precise identity of cGMP targets mediating spinal LTP, their mechanisms of action, and their locus in the spinal circuitry are still unclear. Here, we found that Protein Kinase G1 (PKG-I) localized presynaptically in nociceptor terminals plays an essential role in the expression of spinal LTP. Using the Cre-lox P system, we generated nociceptor-specific knockout mice lacking PKG-I specifically in presynaptic terminals of nociceptors in the spinal cord, but not in post-synaptic neurons or elsewhere (SNS-PKG-I(-/-) mice). Patch clamp recordings showed that activity-induced LTP at identified synapses between nociceptors and spinal neurons projecting to the periaqueductal grey (PAG) was completely abolished in SNS-PKG-I(-/-) mice, although basal synaptic transmission was not affected. Analyses of synaptic failure rates and paired-pulse ratios indicated a role for presynaptic PKG-I in regulating the probability of neurotransmitter release. Inositol 1,4,5-triphosphate receptor 1 and myosin light chain kinase were recruited as key phosphorylation targets of presynaptic PKG-I in nociceptive neurons. Finally, behavioural analyses in vivo showed marked defects in SNS-PKG-I(-/-) mice in several models of activity-induced nociceptive hypersensitivity, and pharmacological studies identified a clear contribution of PKG-I expressed in spinal terminals of nociceptors. Our results thus indicate that presynaptic mechanisms involving an increase in release probability from nociceptors are operational in the expression of synaptic LTP on spinal-PAG projection neurons and that PKG-I localized in presynaptic nociceptor terminals plays an essential role in this process to regulate pain sensitivity.",
"title": "Presynaptically Localized Cyclic GMP-Dependent Protein Kinase 1 Is a Key Determinant of Spinal Synaptic Potentiation and Pain Hypersensitivity"
},
{
"docid": "14711483",
"text": "CONTEXT Vaso-occlusion is central to the painful crises and acute and chronic organ damage in sickle cell disease. Abnormal nitric oxide-dependent regulation of vascular tone, adhesion, platelet activation, and inflammation contributes to the pathophysiology of vaso-occlusion. Nitric oxide may have promise as a mechanism-of-disease-based therapy for treatment of vaso-occlusion. OBJECTIVE To explore the efficacy and safety of inhaled nitric oxide (INO) for treatment of vaso-occlusive crisis in pediatric patients. DESIGN Prospective, double-blind, placebo-controlled, randomized clinical trial with enrollment between September 1999 and October 2001. SETTING Urban, tertiary care children's hospital in the United States. PARTICIPANTS Twenty patients aged 10 to 21 years with sickle cell disease and severe acute vaso-occlusive crisis. INTERVENTION Patients were randomly assigned to receive INO (80 ppm with 21% final concentration of inspired oxygen; n = 10), or placebo (21% inspired oxygen; n = 10) for 4 hours. MAIN OUTCOME MEASURES Change in pain at 4 hours of inhalation compared with preinhalation pain, measured on a 10-cm visual analog scale (VAS); secondary outcome measures were pain over 6 hours, parenteral narcotic use over 24 hours, duration of hospitalization, blood pressure, oxygen saturation, and methemoglobin concentration. RESULTS Preinhalation VAS pain scores were similar in the INO and placebo groups (P =.80). The decrease in VAS pain scores at 4 hours was 2.0 cm in the INO group and 1.2 cm in the placebo group (P =.37). Repeated-measures analysis of variance for hourly pain scores showed a 1-cm/h greater reduction in the INO group than the placebo group (P =.02). Morphine use over 6 hours was significantly less in the INO group (mean cumulative use, 0.29 vs 0.44 mg/kg; P =.03) but was not different over 4 hours (0.26 vs 0.32 mg/kg; P =.21) or 24 hours (0.63 vs 0.91 mg/kg; P =.15). Duration of hospitalization was 78 and 100 hours in the INO and placebo groups, respectively (P =.19). No INO toxicity was observed. CONCLUSIONS Results of this exploratory study suggest that INO may be beneficial for acute vaso-occlusive crisis. These preliminary results warrant further investigation.",
"title": "Preliminary assessment of inhaled nitric oxide for acute vaso-occlusive crisis in pediatric patients with sickle cell disease."
},
{
"docid": "1358909",
"text": "To assess the age- and sex-specific prevalence of peripheral arterial disease (PAD) and intermittent claudication (IC) in an elderly population, we performed a population-based study in 7715 subjects (40% men, 60% women) aged 55 years and over. The presence of PAD and IC was determined by measuring the ankle-arm systolic blood pressure index (AAI) and by means of the World Health Organization/Rose questionnaire, respectively. PAD was considered present when the AAI was <0.90 in either leg. The prevalence of PAD was 19.1% (95% confidence interval, 18.1% to 20.0%): 16.9% in men and 20.5% in women. Symptoms of IC were reported by 1.6% (95% confidence interval, 1.3% to 1.9%) of the study population (2.2% in men, 1.2% in women). Of those with PAD, 6.3% reported symptoms of IC (8.7% in men, 4.9% in women), whereas in 68.9% of those with IC an AAI below 0.90 was found. Subjects with an AAI <0.90 were more likely to be smokers, to have hypertension, and to have symptomatic or asymptomatic cardiovascular disease compared with subjects with an AAI of 0.90 or higher. The authors conclude that the prevalence of PAD in the elderly is high whereas the prevalence of IC is rather low, although both prevalences clearly increase with advancing age. The vast majority of PAD patients reports no symptoms of IC.",
"title": "Peripheral arterial disease in the elderly: The Rotterdam Study."
},
{
"docid": "6309659",
"text": "CONTEXT Exogenous estrogen use may lower risk of dementia in postmenopausal women. A relationship between long-term exposure to endogenous estrogens and incident dementia has been hypothesized but not studied. OBJECTIVE To determine whether a longer reproductive period, as an indicator of longer exposure to endogenous estrogens, is associated with lower risk of dementia and Alzheimer disease (AD) in women who have natural menopause. DESIGN AND SETTING The Rotterdam Study, a population-based prospective cohort study conducted in the Netherlands. PARTICIPANTS A total of 3601 women aged 55 years or older who did not have dementia at baseline (1990-1993) and had information on age at menarche, age at menopause, and type of menopause. Participants were reexamined in 1993-1994 and 1997-1999 and were continuously monitored for development of dementia. MAIN OUTCOME MEASURES Incidence of dementia, based on Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition criteria, and AD, based on National Institute of Neurological Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria, compared by quartiles of reproductive period among women with natural menopause. RESULTS During 21 046 person-years of follow-up (median follow-up, 6.3 years), 199 women developed dementia, including 159 who developed AD. After adjusting for age, dementia was not clearly associated with length of reproductive period. However, after adjusting for multiple covariates, women with natural menopause and more reproductive years had an increased risk of dementia (adjusted rate ratio [RR] for women with >39 reproductive years [highest quartile] compared with <34 reproductive years [lowest quartile], 1.78; 95% confidence interval [CI], 1.12-2.84). The adjusted RR per year of increase was 1.04 (95% CI, 1.01-1.08). For risk of AD, the adjusted RRs were 1.51 (95% CI, 0.91-2.50) and 1.03 (95% CI, 1.00-1.07), respectively. Risk of dementia associated with a longer reproductive period was most pronounced in APOE epsilon4 carriers (adjusted RR for >39 reproductive years compared with <34 reproductive years, 4.20 [95% CI, 1.97-8.92] for dementia and 3.42 [95% CI, 1.51-7.75] for AD), whereas in noncarriers, no clear association with dementia or AD was observed. CONCLUSION Our findings do not support the hypothesis that a longer reproductive period reduces risk of dementia in women who have natural menopause.",
"title": "Reproductive period and risk of dementia in postmenopausal women."
},
{
"docid": "27024392",
"text": "Cannabis has a potential for clinical use often obscured by unreliable and purely anecdotal reports. The most important natural cannabinoid is the psychoactive tetrahydrocannabinol (Δ9-THC); others include cannabidiol (CBD) and cannabigerol (CBG). Not all the observed effects can be ascribed to THC, and the other constituents may also modulate its action; for example CBD reduces anxiety induced by THC. A standardised extract of the herb may be therefore be more beneficial in practice and clinical trial protocols have been drawn up to assess this. The mechanism of action is still not fully understood, although cannabinoid receptors have been cloned and natural ligands identified. Cannabis is frequently used by patients with multiple sclerosis (MS) for muscle spasm and pain, and in an experimental model of MS low doses of cannabinoids alleviated tremor. Most of the controlled studies have been carried out with THC rather than cannabis herb and so do not mimic the usual clincal situation. Small clinical studies have confirmed the usefulness of THC as an analgesic; CBD and CBG also have analgesic and antiinflammatory effects, indicating that there is scope for developing drugs which do not have the psychoactive properties ofTHC. Patients taking the synthetic derivative nabilone for neurogenic pain actually preferred cannabis herb and reported that it relieved not only pain but the associated depression and anxiety. Cannabinoids are effective in chemotherapy-induced emesis and nabilone has been licensed for this use for several years. Currently, the synthetic cannabinoid HU211 is undergoing trials as a protective agent after brain trauma. Anecdotal reports of cannabis use include case studies in migraine and Tourette’s syndrome, and as a treatment for asthma and glaucoma. Apart from the smoking aspect, the safety profile of cannabis is fairly good. However, adverse reactions include panic or anxiety attacks, which are worse in the elderly and in women, and less likely in children. Although psychosis has been cited as a consequence of cannabis use, an examination of psychiatric hospital admissions found no evidence of this, however, it may exacerbate existing symptoms. The relatively slow elimination from the body of the cannabinoids has safety implications for cognitive tasks, especially driving and operating machinery; although driving impairment with cannabis is only moderate, there is a significant interaction with alcohol. Natural materials are highly variable and multiple components need to be standardised to ensure reproducible effects. Pure natural and synthetic compounds do not have these disadvantages but may not have the overall therapeutic effect of the herb.",
"title": "Cannabinoids in Clinical Practice"
},
{
"docid": "41493639",
"text": "Burns are one of the most devastating conditions encountered in medicine. The injury represents an assault on all aspects of the patient, from the physical to the psychological. It affects all ages, from babies to elderly people, and is a problem in both the developed and developing world. All of us have experienced the severe pain that even a small burn can bring. However the pain and distress caused by a large burn are not limited to the immediate event. The visible physical and the invisible psychological scars are long lasting and often lead to chronic disability. Burn injuries represent a diverse and varied challenge to medical and paramedical staff. Correct management requires a skilled multidisciplinary approach that addresses all the problems facing a burn patient. This series provides an overview of the most important aspects of burn injuries for hospital and non-hospital healthcare workers.workers. Figure 1 Top: Child with 70% full thickness burns, which required resuscitation, intensive care support, and extensive debridement and skin grafting. Left: The same child one year later at a burns camp, having made a good recovery. A reasonable outcome is possible ...",
"title": "ABC of burns. Introduction."
},
{
"docid": "24704139",
"text": "OBJECTIVE The Diabetes Prevention Program (DPP) is a 27-center randomized clinical trial designed to evaluate the safety and efficacy of interventions that may delay or prevent development of diabetes in people at increased risk for type 2 diabetes. RESEARCH DESIGN AND METHODS Eligibility requirements were age > or = 25 years, BMI > or = 24 kg/m2 (> or = 22 kg/m2 for Asian-Americans), and impaired glucose tolerance plus a fasting plasma glucose of 5.3-6.9 mmol/l (or < or = 6.9 mmol for American Indians). Randomization of participants into the DPP over 2.7 years ended in June 1999. Baseline data for the three treatment groups--intensive lifestyle modification, standard care plus metformin, and standard care plus placebo--are presented for the 3,234 participants who have been randomized. RESULTS Of all participants , 55% were Caucasian, 20% were African-American, 16% were Hispanic, 5% were American Indian, and 4% were Asian-American. Their average age at entry was 51 +/- 10.7 years (mean +/- SD), and 67.7% were women. Moreover, 16% were < 40 years of age, and 20% were > or = 60 years of age. Of the women, 48% were postmenopausal. Men and women had similar frequencies of history of hypercholesterolemia (37 and 33%, respectively) or hypertension (29 and 26%, respectively). On the basis of fasting lipid determinations, 54% of men and 40% of women fit National Cholesterol Education Program criteria for abnormal lipid profiles. More men than women were current or former cigarette smokers or had a history of coronary heart disease. Furthermore, 66% of men and 71% of women had a first-degree relative with diabetes. Overall, BMI averaged 34.0 +/- 6.7 kg/m2 at baseline with 57% of the men and 73% of women having a BMI > or = 30 kg/m2. Average fasting plasma glucose (6.0 +/- 0.5 mmol/l) and HbA1c (5.9 +/- 0.5%) in men were comparable with values in women (5.9 +/- 0.4 mmol/l and 5.9 +/- 0.5%, respectively). CONCLUSIONS The DPP has successfully randomized a large cohort of participants with a wide distribution of age, obesity, and ethnic and racial backgrounds who are at high risk for developing type 2 diabetes. The study will examine the effects of interventions on the development of diabetes.",
"title": "The Diabetes Prevention Program: baseline characteristics of the randomized cohort. The Diabetes Prevention Program Research Group."
},
{
"docid": "17821387",
"text": "In Parkinson's disease (PD) and dementia with Lewy bodies (DLB) alpha-synuclein (alphaS) pathology is seen that displays a predictable topographic distribution. There are two staging/categorization systems, i.e. Braak's and McKeith's, currently in use for the assessment of alphaS pathology. The aim of these diagnostic strategies in pathology is, in addition to assess the stage/severity of pathology, to assess the probabilities of the related clinical symptomatology i.e. dementia and extrapyramidal symptoms (EPS). Herein, we assessed the applicability of these two staging/categorization systems and the frequency of dementia and EPS in a cohort of 226 alphaS-positive-subjects. These subject were selected from a large autopsy sample (n = 1,720), irrespective of the clinical presentation, based on the detection of alphaS-immunoreactivity (IR) in one of the most vulnerable nuclei; in the dorsal motor nucleus of vagus, substantia nigra and basal forebrain. The frequency of alphaS-IR lesions in this large cohort was 14% (248 out of 1,720). If applicable, each of the 226 subjects with all required material available was assigned a neuropathological stage/category of PD/DLB and finally the neuropathological data was analyzed in relation to dementia and EPS. 83% of subjects showed a distribution pattern of alphaS-IR that was compatible with the current staging/categorization systems. Around 55% of subjects with widespread alphaS pathology (Braak's PD stages 5-6) lacked clinical signs of dementia or EPS. Similarly, in respect to those subjects that fulfilled the McKeith criteria for diffuse neocortical category and displaying only mild concomitant Alzheimer's disease-related pathology, only 48% were demented and 54% displayed EPS. It is noteworthy that some subjects (17%) deviated from the suggested caudo-rostral propagation suggesting alternative routes of progression, perhaps due to concomitant diseases and genetic predisposition. In conclusion, our results do indeed confirm that current staging/categorization systems can readily be applied to most of the subjects with alphaS pathology. However, finding that around half of the subjects with abundant alphaS pathology remain neurologically intact is intriguing and raises the question whether we do assess the actual disease process.",
"title": "Applicability of current staging/categorization of α-synuclein pathology and their clinical relevance"
},
{
"docid": "116556376",
"text": "BACKGROUND Little information is available on physician characteristics and patient presentations that may influence compliance with evidence-based guidelines for acute low back pain. OBJECTIVE To assess whether physicians' management decisions are consistent with the Agency for Health Research Quality's guideline and whether responses varied with the presentation of sciatica or by physician characteristics. DESIGN Cross-sectional study using a mailed survey. PARTICIPANTS Participants were randomly selected from internal medicine, family practice, general practice, emergency medicine, and occupational medicine specialties. MEASUREMENTS A questionnaire asked for recommendations for 2 case scenarios, representing patients without and with sciatica, respectively. RESULTS Seven hundred and twenty surveys were completed (response rate=25%). In cases 1 (without sciatica) and 2 (with sciatica), 26.9% and 4.3% of physicians fully complied with the guideline, respectively. For each year in practice, the odds of guideline noncompliance increased 1.03 times (95% confidence interval [CI]=1.01 to 1.05) for case 1. With occupational medicine as the referent specialty, general practice had the greatest odds of noncompliance (3.60, 95% CI=1.75 to 7.40) in case 1, followed by internal medicine and emergency medicine. Results for case 2 reflected the influence of sciatica with internal medicine having substantially higher odds (vs case 1) and the greatest odds of noncompliance of any specialty (6.93, 95% CI=1.47 to 32.78), followed by family practice and emergency medicine. CONCLUSIONS A majority of primary care physicians continue to be noncompliant with evidence-based back pain guidelines. Sciatica dramatically influenced clinical decision-making, increasing the extent of noncompliance, particularly for internal medicine and family practice. Physicians' misunderstanding of sciatica's natural history and belief that more intensive initial management is indicated may be factors underlying the observed influence of sciatica.",
"title": "Physicians' initial management of acute low back pain versus evidence-based guidelines. Influence of sciatica."
},
{
"docid": "1522647",
"text": "BACKGROUND Mitochondrial DNA (mtDNA) is a critical activator of inflammation and the innate immune system. However, mtDNA level has not been tested for its role as a biomarker in the intensive care unit (ICU). We hypothesized that circulating cell-free mtDNA levels would be associated with mortality and improve risk prediction in ICU patients. METHODS AND FINDINGS Analyses of mtDNA levels were performed on blood samples obtained from two prospective observational cohort studies of ICU patients (the Brigham and Women's Hospital Registry of Critical Illness [BWH RoCI, n = 200] and Molecular Epidemiology of Acute Respiratory Distress Syndrome [ME ARDS, n = 243]). mtDNA levels in plasma were assessed by measuring the copy number of the NADH dehydrogenase 1 gene using quantitative real-time PCR. Medical ICU patients with an elevated mtDNA level (≥3,200 copies/µl plasma) had increased odds of dying within 28 d of ICU admission in both the BWH RoCI (odds ratio [OR] 7.5, 95% CI 3.6-15.8, p = 1×10(-7)) and ME ARDS (OR 8.4, 95% CI 2.9-24.2, p = 9×10(-5)) cohorts, while no evidence for association was noted in non-medical ICU patients. The addition of an elevated mtDNA level improved the net reclassification index (NRI) of 28-d mortality among medical ICU patients when added to clinical models in both the BWH RoCI (NRI 79%, standard error 14%, p<1×10(-4)) and ME ARDS (NRI 55%, standard error 20%, p = 0.007) cohorts. In the BWH RoCI cohort, those with an elevated mtDNA level had an increased risk of death, even in analyses limited to patients with sepsis or acute respiratory distress syndrome. Study limitations include the lack of data elucidating the concise pathological roles of mtDNA in the patients, and the limited numbers of measurements for some of biomarkers. CONCLUSIONS Increased mtDNA levels are associated with ICU mortality, and inclusion of mtDNA level improves risk prediction in medical ICU patients. Our data suggest that mtDNA could serve as a viable plasma biomarker in medical ICU patients.",
"title": "Circulating Mitochondrial DNA in Patients in the ICU as a Marker of Mortality: Derivation and Validation"
},
{
"docid": "8582337",
"text": "IMPORTANCE Understanding the major health problems in the United States and how they are changing over time is critical for informing national health policy. OBJECTIVES To measure the burden of diseases, injuries, and leading risk factors in the United States from 1990 to 2010 and to compare these measurements with those of the 34 countries in the Organisation for Economic Co-operation and Development (OECD) countries. DESIGN We used the systematic analysis of descriptive epidemiology of 291 diseases and injuries, 1160 sequelae of these diseases and injuries, and 67 risk factors or clusters of risk factors from 1990 to 2010 for 187 countries developed for the Global Burden of Disease 2010 Study to describe the health status of the United States and to compare US health outcomes with those of 34 OECD countries. Years of life lost due to premature mortality (YLLs) were computed by multiplying the number of deaths at each age by a reference life expectancy at that age. Years lived with disability (YLDs) were calculated by multiplying prevalence (based on systematic reviews) by the disability weight (based on population-based surveys) for each sequela; disability in this study refers to any short- or long-term loss of health. Disability-adjusted life-years (DALYs) were estimated as the sum of YLDs and YLLs. Deaths and DALYs related to risk factors were based on systematic reviews and meta-analyses of exposure data and relative risks for risk-outcome pairs. Healthy life expectancy (HALE) was used to summarize overall population health, accounting for both length of life and levels of ill health experienced at different ages. RESULTS US life expectancy for both sexes combined increased from 75.2 years in 1990 to 78.2 years in 2010; during the same period, HALE increased from 65.8 years to 68.1 years. The diseases and injuries with the largest number of YLLs in 2010 were ischemic heart disease, lung cancer, stroke, chronic obstructive pulmonary disease, and road injury. Age-standardized YLL rates increased for Alzheimer disease, drug use disorders, chronic kidney disease, kidney cancer, and falls. The diseases with the largest number of YLDs in 2010 were low back pain, major depressive disorder, other musculoskeletal disorders, neck pain, and anxiety disorders. As the US population has aged, YLDs have comprised a larger share of DALYs than have YLLs. The leading risk factors related to DALYs were dietary risks, tobacco smoking, high body mass index, high blood pressure, high fasting plasma glucose, physical inactivity, and alcohol use. Among 34 OECD countries between 1990 and 2010, the US rank for the age-standardized death rate changed from 18th to 27th, for the age-standardized YLL rate from 23rd to 28th, for the age-standardized YLD rate from 5th to 6th, for life expectancy at birth from 20th to 27th, and for HALE from 14th to 26th. CONCLUSIONS AND RELEVANCE From 1990 to 2010, the United States made substantial progress in improving health. Life expectancy at birth and HALE increased, all-cause death rates at all ages decreased, and age-specific rates of years lived with disability remained stable. However, morbidity and chronic disability now account for nearly half of the US health burden, and improvements in population health in the United States have not kept pace with advances in population health in other wealthy nations.",
"title": "The state of US health, 1990-2010: burden of diseases, injuries, and risk factors."
}
] |
9460
|
Finding Uncorrelated Assets
|
[
{
"docid": "449043",
"text": "Have a look at: Diversify Portfolio. The site provides various tools all focused on correlation, diversification and portfolio construction. You can scan through every stock and ETF listed on the NASDAQ and NYSE to find any kind of correlation you're looking for. You can also create a portfolio and then analyze all the correlations within it, or search for specific stocks that can be added to the portfolio based on correlation and various other factors.",
"title": ""
}
] |
[
{
"docid": "7845",
"text": "\"These days almost all risky assets move together, so the most difficult criterion to match from your 4 will be \"\"not strongly correlated to the U.S. economy.\"\" However, depending on how you define \"\"strongly,\"\" you may want to consider the following: Be careful, you are sort of asking for the impossible here, so these will all be caveat emptor type assets. EDIT: A recent WSJ article talks about what some professional investors are doing to find uncorrelated bets. Alfredo Viegas, an emerging-markets strategist for boutique brokerage Knight Capital Group, is encouraging clients to bet against Israeli bonds. His theory: Investors are so focused on Europe that they are misjudging risks in the Middle East, such as a flare-up in relations between Israel and Iran, or greater conflict in Egypt and Syria. Once they wake up to those risks, Israeli bonds are likely to tumble, Mr. Viegas reasons. In the meantime, the investment isn't likely to be pushed one way or another by the European crisis, he says.\"",
"title": ""
},
{
"docid": "180855",
"text": "Diversifying your portfolio between asset A and asset B only reduces the portfolio risk if asset A and asset B are not correlated. If they have either a low correlation or a negative correlation to each other, then you benefit from combining them in a portfolio in terms of risk reduction. The standard deviation of returns will be lower in a portfolio of low or uncorrelated assets. If on the other hand you combine two correlated assets into a portfolio you are doubling down on the same assumption, which means you are not reducing your risk. You are also wasting capital because now you have allocated capital to 2 separate trades / investments yet they have shown a high tendency of moving together. Here is an article that discusses this further: Why Diversify your Stock Portfolio",
"title": ""
},
{
"docid": "425452",
"text": "\"In theory, the idea is that diversified assets will perform differently in different circumstances, spreading your risk around. Whether that still functions in practice is a decent question, as the \"\"truth\"\" of most probability based arguments for diversification rely on the different assets being at least somewhat uncorrelated. This article suggests that might not be true. Specifically: The correlations we note among industry sectors are profoundly and dysfunctionally high. and Gold and silver traders have gotten too used to the negative correlation trade with stocks. This is, in fact, an unusual relationship for precious metals tostocks. The correlation should actually be zero.\"",
"title": ""
},
{
"docid": "463837",
"text": "\"John Bensin's answer covers the math, but I like the plain-English examples of the theory from William Bernstein's fine book, The Intelligent Asset Allocator. At the author's web site, you can find the complete chapter 1 and chapter 2, though not chapter 3, which is the one with the \"\"multiple coin toss\"\" portfolio example I want to highlight. I'll summarize Bernstein's multiple coin toss example here with some excerpts from the book. (Another top user, @JoeTaxpayer, has also written about the coin flip on his blog, also mentioning Bernstein's book.) Bernstein begins Chapter 1 by describing an offer from a fictitious \"\"Uncle Fred\"\": Imagine that you work for your rich but eccentric Uncle Fred. [...] he decides to let you in on the company pension plan. [...] you must pick ahead of time one of two investment choices for the duration of your employment: Certificates of deposit with a 3% annualized rate of return, or, A most peculiar option: At the end of each year Uncle Fred flips a coin. Heads you receive a 30% investment return for that year, tails a minus 10% (loss) for the year. This will be hereafter referred to as \"\"Uncle Fred’s coin toss,\"\" or simply, the \"\"coin toss.\"\" In effect, choosing option 2 results in a higher expected return than option 1, but it is certainly riskier, having a high standard deviation and being especially prone to a series of bad tosses. Chapters 1 and 2 continue to expand on the idea of risk, and take a look at various assets/markets over time. Chapter 3 then begins by introducing the multiple coin toss example: Time passes. You have spent several more years in the employ of your Uncle Fred, and have truly grown to dread the annual coin-toss sessions. [...] He makes you another offer. At the end of each year, he will divide your pension account into two equal parts and conduct a separate coin toss for each half [...] there are four possible outcomes [...]: [...] Being handy with numbers, you calculate that your annualized return for this two-coin-toss sequence is 9.08%, which is nearly a full percentage point higher than your previous expected return of 8.17% with only one coin toss. Even more amazingly, you realize that your risk has been reduced — with the addition of two returns at the mean of 10%, your calculated standard deviation is now only 14.14%, as opposed to 20% for the single coin toss. [...] Dividing your portfolio between assets with uncorrelated results increases return while decreasing risk. [...] If the second coin toss were perfectly inversely correlated with the first and always gave the opposite result [hence, outcomes 1 and 4 above never occurring], then our return would always be 10%. In this case, we would have a 10% annualized long-term return with zero risk! I hope that summarizes the example well. Of course, in the real world, one of the tricks to building a good portfolio is finding assets that aren't well-correlated, and if you're interested in more on the subject I suggest you check out his books (including The Four Pillars of Investing) and read more about Modern Portfolio Theory (MPT).\"",
"title": ""
},
{
"docid": "113786",
"text": "\"There are two umbrellas in investing: active management and passive management. Passive management is based on the idea \"\"you can't beat the market.\"\" Passive investors believe in the efficient markets hypothesis: \"\"the market interprets all information about an asset, so price is equal to underlying value\"\". Another idea in this field is that there's a minimum risk associated with any given return. You can't increase your expected return without assuming more risk. To see it graphically: As expected return goes up, so does risk. If we stat with a portfolio of 100 bonds, then remove 30 bonds and add 30 stocks, we'll have a portfolio that's 70% bonds/30% stocks. Turns out that this makes expected return increase and lower risk because of diversification. Markowitz showed that you could reduce the overall portfolio risk by adding a riskier, but uncorrelated, asset! Basically, if your entire portfolio is US stocks, then you'll lose money whenever US stocks fall. But, if you have half US stocks, quarter US bonds, and quarter European stocks, then even if the US market tanks, half your portfolio will be unaffected (theoretically). Adding different types of uncorrelated assets can reduce risk and increase returns. Let's tie this all together. We should get a variety of stocks to reduce our risk, and we can't beat the market by security selection. Ideally, we ought to buy nearly every stock in the market so that So what's our solution? Why, the exchange traded fund (ETF) of course! An ETF is basically a bunch of stocks that trade as a single ticker symbol. For example, consider the SPDR S&P 500 (SPY). You can purchase a unit of \"\"SPY\"\" and it will move up/down proportional to the S&P 500. This gives us diversification among stocks, to prevent any significant downside while limiting our upside. How do we diversify across asset classes? Luckily, we can purchase ETF's for almost anything: Gold ETF's (commodities), US bond ETF's (domestic bonds), International stock ETFs, Intl. bonds ETFs, etc. So, we can buy ETF's to give us exposure to various asset classes, thus diversifying among asset classes and within each asset class. Determining what % of our portfolio to put in any given asset class is known as asset allocation and some people say up to 90% of portfolio returns can be determined by asset allocation. That pretty much sums up passive management. The idea is to buy ETFs across asset classes and just leave them. You can readjust your portfolio holdings periodically, but otherwise there is no rapid trading. Now the other umbrella is active management. The unifying idea is that you can generate superior returns by stock selection. Active investors reject the idea of efficient markets. A classic and time proven strategy is value investing. After the collapse of 07/08, bank stocks greatly fell, but all the other stocks fell with them. Some stocks worth $100 were selling for $50. Value investors quickly snapped up these stocks because they had a margin of safety. Even if the stock didn't go back to 100, it could go up to $80 or $90 eventually, and investors profit. The main ideas in value investing are: have a big margin of safety, look at a company's fundamentals (earnings, book value, etc), and see if it promises adequate return. Coke has tremendous earnings and it's a great company, but it's so large that you're never going to make 20% profits on it annually, because it just can't grow that fast. Another field of active investing is technical analysis. As opposed to the \"\"fundamental analysis\"\" of value investing, technical analysis involves looking at charts for patterns, and looking at stock history to determine future paths. Things like resistance points and trend lines also play a role. Technical analysts believe that stocks are just ticker symbols and that you can use guidelines to predict where they're headed. Another type of active investing is day trading. This basically involves buying and selling stocks every hour or every minute or just at a rapid pace. Day traders don't hold onto investments for very long, and are always trying to predict the market in the short term and take advantage of it. Many individual investors are also day traders. The other question is, how do you choose a strategy? The short answer is: pick whatever works for you. The long answer is: Day trading and technical analysis is a lot of luck. If there are consistent systems for trading , then people are keeping them secret, because there is no book that you can read and become a consistent trader. High frequency trading (HFT) is an area where people basically mint money, but it s more technology and less actual investing, and would not be categorized as day trading. Benjamin Graham once said: In the short run, the market is a voting machine but in the long run it is a weighing machine. Value investing will work because there's evidence for it throughout history, but you need a certain temperament for it and most people don't have that. Furthermore, it takes a lot of time to adequately study stocks, and people with day jobs can't devote that kind of time. So there you have it. This is my opinion and by no means definitive, but I hope you have a starting point to continue your study. I included the theory in the beginning because there are too many monkeys on CNBC and the news who just don't understand fundamental economics and finance, and there's no sense in applying a theory until you can understand why it works and when it doesn't.\"",
"title": ""
},
{
"docid": "443926",
"text": "If there are no traded options in a company you can get your broker to write OTC options but this may not be possible given some restrictions on accounts. Going short on futures may also be an option. You can also open a downside CFD (contract for difference) on the stock but will have to have margin posted against it so will have to hold cash (or possibly liquid assets if your AUM is large enough) to cover the margin which is unutilized cash in the portfolio that needs to be factored into any portfolio calculations as a cost. Diversifying into uncorrelated stock or shorting correlated (but low div yield) stock would also have the same effect. stop loss orders would probably not be appropriate as it is not the price of the stock that you are concerned with but mitigating all price changes and just receiving the dividend on the stock. warning: in a crash (almost) all stocks become suddenly correlated so be aware that might cause you a short term loss. CFDs are complex and require a degree of sophistication before you can trade them well but as you seem to understand options they should not be too hard to understand.",
"title": ""
},
{
"docid": "485760",
"text": "\"Do you want to do it pre or post correction? If you're bearish on the market the obvious thing to do is short an index. I would say this is kind of dumb. The main problem is that it may take months or years for the market to crash, and by then it will have gone up so much that even the crash doesn't bring you profit, and you're paying borrowing fees meanwhile as well. You need to watch the portfolio also, when you short sell you'll get a bunch of cash, which you most likely will want to invest, but once you invest it, the market can spike and pummel your short position, resulting in negative remaining cash (since you already spent it). At that point you get a margin call from your broker. If you check your account regularly, not a big deal, but bad things can happen if you treat it as a fire and forget strategy. These days they have inverse funds so you don't have to borrow anything. The fund manager borrows for you. I'd say those are much better. The less cumbersome choice is to simply sell call options on the index or buy puts. These are even cash options, so when you exercise you get/lose money, not shares. You can even arrange them so that your potential loss is capped. (but honestly, same goes for shorts - it's called a stop loss) You could also wait for the correction and buy the dip. Less worrying about shorts and such, but of course the issue is timing the crash. Usually the crashes are very quick, and there are several \"\"pre-crashes\"\" that look like it bottomed out but then it crashes more. So actually very difficult thing to tell. You have to know either exactly when the correction will be, or exactly what the price floor is (and set a limit buy). Hope your crystal ball works! Yet another choice is finding asset classes uncorrelated or even anticorrelated with the broader market. For instance some emerging markets (developing countries), some sectors, individual stocks that are not inflated, bonds, gold and so on can have these characteristics where if S&P goes down they go up. Buying those may be a safer approach since at least you are still holding a fundamentally valuable thing even if your thesis flops, meanwhile shorts and puts and the like are purely speculative.\"",
"title": ""
},
{
"docid": "542795",
"text": "So I did some queries on Google Scholar, and the term of art academics seem to use is target date fund. I notice divided opinions among academics on the matter. W. Pfau gave a nice set of citations of papers with which he disagrees, so I'll start with them. In 1969, Paul Sameulson published the paper Lifetime Portfolio Selection By Dynamic Stochaistic Programming, which found that there's no mathematical foundation for an age based risk tolerance. There seems to be a fundamental quibble relating to present value of future wages; if they are stable and uncorrelated with the market, one analysis suggests the optimal lifecycle investment should start at roughly 300 percent of your portfolio in stocks (via crazy borrowing). Other people point out that if your wages are correlated with stock returns, allocations to stock as low as 20 percent might be optimal. So theory isn't helping much. Perhaps with the advent of computers we can find some kind of empirical data. Robert Shiller authored a study on lifecycle funds when they were proposed for personal Social Security accounts. Lifecycle strategies fare poorly in his historical simulation: Moreover, with these life cycle portfolios, relatively little is contributed when the allocation to stocks is high, since earnings are relatively low in the younger years. Workers contribute only a little to stocks, and do not enjoy a strong effect of compounding, since the proceeds of the early investments are taken out of the stock market as time goes on. Basu and Drew follow up on that assertion with a set of lifecycle strategies and their contrarian counterparts: whereas a the lifecycle plan starts high stock exposure and trails off near retirement, the contrarian ones will invest in bonds and cash early in life and move to stocks after a few years. They show that contrarian strategies have higher average returns, even at the low 25th percentile of returns. It's only at the bottom 5 or 10 percent where this is reversed. One problem with these empirical studies is isolating the effect of the glide path from rebalancing. It could be that a simple fixed allocation works plenty fine, and that selling winners and doubling down on losers is the fundamental driver of returns. Schleef and Eisinger compare lifecycle strategy with a number of fixed asset allocation schemes in Monte Carlo simulations and conclude that a 70% equity, 30% long term corp bonds does as well as all of the lifecycle funds. Finally, the earlier W Pfau paper offers a Monte Carlo simulation similar to Schleef and Eisinger, and runs final portfolio values through a utility function designed to calculate diminishing returns to more money. This seems like a good point, as the risk of your portfolio isn't all or nothing, but your first dollar is more valuable than your millionth. Pfau finds that for some risk-aversion coefficients, lifecycles offer greater utility than portfolios with fixed allocations. And Pfau does note that applying their strategies to the historical record makes a strong recommendation for 100 percent stocks in all but 5 years from 1940-2011. So maybe the best retirement allocation is good old low cost S&P index funds!",
"title": ""
},
{
"docid": "470758",
"text": "\"One approach is to invest in \"\"allocation\"\" mutual funds that use various methods to vary their asset allocation. Some examples (these are not recommendations; just to show you what I am talking about): A good way to identify a useful allocation fund is to look at the \"\"R-squared\"\" (correlation) with indexes on Morningstar. If the allocation fund has a 90-plus R-squared with any index, it probably isn't doing a lot. If it's relatively uncorrelated, then the manager is not index-hugging, but is making decisions to give you different risks from the index. If you put 10% of your portfolio in a fund that varies allocation to stocks from 25% to 75%, then your allocation to stocks created by that 10% would be between 2.5% to 7.5% depending on the views of the fund manager. You can use that type of calculation to invest enough in allocation funds to allow your overall allocation to vary within a desired range, and then you could put the rest of your money in index funds or whatever you normally use. You can think of this as diversifying across investment discipline in addition to across asset class. Another approach is to simply rely on your already balanced portfolio and enjoy any downturns in stocks as an opportunity to rebalance and buy some stocks at a lower price. Then enjoy any run-up as an opportunity to rebalance and sell some stocks at a high price. The difficulty of course is going through with the rebalance. This is one advantage of all-in-one funds (target date, \"\"lifecycle,\"\" balanced, they have many names), they will always go through with the rebalance for you - and you can't \"\"see\"\" each bucket in order to get stressed about it. i.e. it's important to think of your portfolio as a whole, not look at the loss in the stocks portion. An all-in-one fund keeps you from seeing the stocks-by-themselves loss number, which is a good way to trick yourself into behaving sensibly. If you want to rebalance \"\"more aggressively\"\" then look at value averaging (search for \"\"value averaging\"\" on this site for example). A questionable approach is flat-out market-timing, where you try to get out and back in at the right times; a variation on this would be to buy put options at certain times; the problem is that it's just too hard. I think it makes more sense to buy an allocation fund that does this for you. If you do market time, you want to go in and out gradually, and value averaging is one way to do that.\"",
"title": ""
},
{
"docid": "440418",
"text": "Yah, I haven't played in this space very much. My only exposure was visiting a weather insurance company who wanted the fund I was at to take the other side of their bets - paying us a fixed amount and having us cover them whenever their losses were over a certain amount for the month. It looked like a pretty bad deal, but apparently some multi-strat hedge-fund eventually went with it for the uncorrelated beta.",
"title": ""
},
{
"docid": "247614",
"text": "\"My two cents: I am a pension actuary and see the performance of funds on a daily basis. Is it normal to see down years? Yes, absolutely. It's a function of the directional bias of how the portfolio is invested. In the case of a 401(k) that almost always mean a positive directional bias (being long). Now, in your case I see two issues: The amount of drawdown over one year. It is atypical to have a 14% loss in a little over a year. Given the market conditions, this means that you nearly experienced the entire drawdown of the SP500 (which your portfolio is highly correlated to) and you have no protection from the downside. The use of so-called \"\"target-date funds\"\". Their very implication makes no sense. Essentially, they try to generate a particular return over the elapsed time until retirement. The issue is that the market is by all statistical accounts random with positive drift (it can be expected to move up in the long term). This positive drift is due to the fact that people should be paid to take on risk. So if you need the money 20 years from now, what's the big deal? Well, the issue is that no one, and I repeat, no one, knows when the market will experience long down moves. So you happily experience positive drift for 20 years and your money grows to a decent size. Then, right before you retire, the market shaves 20%+ of your investments. Will you recoup these damages? Most likely yes. But will that be in the timeframe you need? The market doesn't care if you need money or not. So, here is my advice if you are comfortable taking control of your money. See if you can roll your money into an IRA (some 401(k) plans will permit this) or, if you contribute less that the 401(k) contribution limit you make want to just contribute to an IRA (be mindful of the annual limits). In this case, you can set up a self-directed account. Here you will have the flexibility to diversify and take action as necessary. And by diversify, I don't mean that \"\"buy lots of different stuff\"\" garbage, I mean focus on uncorrelated assets. You can get by on a handful of ETFs (SPY, TLT, QQQ, ect.). These all have liquid options available. Once you build a base, you can lower basis by writing covered calls against these positions. This is allowed in almost all IRA accounts. In my opinion, and I see this far too often, your potential and drive to take control of your assets is far superior than the so called \"\"professionals or advisors\"\". They will 99% of the time stick you in a target date fund and hope that they make their basis points on your money and retire before you do. Not saying everyone is unethical, but its hard to care about your money more than you will.\"",
"title": ""
},
{
"docid": "342025",
"text": "You can think of a free cash flow as dividends from operations. FCF = cash from operations - investment in operations. The present value of these cash flows into the future is the value of the firm (DCF is very much like the dividend discount model). Now why does a DCF produce enterprise value and not equity value? Because a DCF values the firm's operating assets. To find the equity value, you use the accounting relation: assets = liabilities + equity (or in financial terms net operating assets = net financial obligations + common stockholders equity). This means you take away net debt from the value produced by the DCF to find equity. Now all your excess cash is netted off against your financial obligations (debt) to find the net debt. Cash used for day to day operations is an operating asset and should be treated as such, operating cash should not deducted from value of assets when finding the value of equity. At least that's what they're teaching at university now (i'm a uni student who's just finished my business valuation subject).",
"title": ""
},
{
"docid": "274870",
"text": "\"Mortgage is a (secured) debt, a combination of a promissory note, and a security interest providing the mortage holder a secured interest in the property. Yes, you are \"\"in debt\"\". But that depends upon whether you define the term \"\"in debt\"\" as a debt appearing on the balance sheet, or the net of assets - liabilities is less than zero, whether you have a \"\"debt\"\" expense on the income statement (budget), or whether the net of income - expenses is less than zero. One person might look at their budget, find the (monthly) mortgage payment listed, and judge that they have a debt payment, and thus are \"\"in debt\"\". Or they might look at their expenses, find they exceed their income, and judge that they are \"\"in debt\"\". Another person might look at their balance sheet, compare assets to liabilities, and only say they were \"\"in debt\"\" when their liabilities exceeded their assets. Some people view mortgage debt as \"\"good debt\"\", as they view certain debts as \"\"good\"\" and others as \"\"bad\"\". Trust me, having a high mortgage payment (higher 30% of your net income) is hard, and over 40% is bad. Consider you balance sheet and your income statement. On your balance sheet, the house appears on the \"\"asset\"\" side with an (estimated) value, while the \"\"mortgage\"\" (really, the promissory note part of the mortgage) appears on the \"\"liability\"\" side. On your income statement, your house does not appear on the income side, but the mortgage (promissory note) payment appears on the expense side. So, you clearly have both a \"\"liability\"\" with a clearly-defined value and an \"\"expense\"\" with a clearly-defined payment. But do you have an \"\"asset\"\"? According to an accountant, you have an \"\"asset\"\" and a \"\"liability\"\". But you do not have a business asset that is producing revenue (income), nor do you have a business asset that can be amortized and expensed to reduce taxable income. When we think about an asset, does the word have the connotation of some thing with value, something that produces income? Well, by that measure, a house only provides income when we rent it out, and only has value when we consider selling it. As millions of families discovered during the housing (price) collapse, when the market price of your \"\"asset\"\" falls substantially, your personal financial status can fall negative and you can be \"\"broke\"\".\"",
"title": ""
},
{
"docid": "575417",
"text": "\"It appears as others have said that companies are not required to state this on as any sort of Asset. I remembered a friend of mine is a lawyer specializing in Intellectual Property Rights so asked him and confirmed that there's no document companies are required to file which states all patent holdings as assets. There are two ways he suggested for finding out. Once you find a company you're interested in can search patents by company using one of the two following: US Patent Office website's advanced search: http://patft.uspto.gov/netahtml/PTO/search-adv.htm aanm/company for example entering into the textarea, \"\"aanm/google\"\" without the quotation marks will find patents by Google. The other is a Google Patent Search: http://www.google.com/patents/\"",
"title": ""
},
{
"docid": "588481",
"text": "\"I think you're on the wrong track. Getting more and more samples from the real world does not make your backtest more accurate, it just confirms that your strategy can withstand one particular sample path of a stochastic process. The reason why you find it simple to incorporate fees, commissions, taxes, etc. is because they're a static and constant process -- well they might change over time but most definitely uncorrelated to the markets. Modelling overnight returns or the top levels of the order book the next day is serious work. First you have to select a suitable model (that's mostly theoretical work but experience can help a lot). Then, in order to do it data-driven, you'd have to plough through thousands of days of sample data on a set of thousands of instruments to get a \"\"feeling\"\" (aka significant model parameters). Apropos data mining, I think Excel might be the wrong tool for the job. Level-2 data (even just the first 10 levels) is a massive blob. For example, the NYSE OpenBook historical data weighs in at a massive 15 TB compressed (uncompressed 74 TB) for the last 10 years, and costs USD 200k. Anyway, as for other factors to take into account: So how to account for all this in a backtest? Personally, I would put in some penalty terms (as % on a return basis) for every factor you want to consider, don't hardcode them. You can then run a stress test by exploring these parameters (i.e. assign some values in the range of 0 to whatever fits). Explore them individually (only set one penalty term at a time) to get a feeling how the strategy might react to stress from that factor. Then you can run the backtest with typical (or observed) combinations of penalty factors and slowly stress them altogether. Edit Just to avoid confusion about terminology. A backtest in the strict sense (had I implemented this strategy X years ago, what would have happened?) won't benefit from any modelling simply because the real-world \"\"does the sampling\"\" for us. However, to evaluate a strategy's robustness you should account for the additional factors and run some stress tests. If the strategy performs well in the real-world or no-stress scenario but produces losses once a tiny slippage occurs every now and again, you could conclude that the strategy is very fragile. The key is to explore the maximum stress the strategy can handle (by whatever measure); if a lot you can call the strategy robust. The latter is what I personally call a backtest; the first procedure would go by the name \"\"extension towards the past\"\" or so. Some lightweight literature:\"",
"title": ""
},
{
"docid": "186805",
"text": ">Conclusion >Covert operations organized and abetted by foreign governments have played a substantial role in the political and economic development of poorer countries around the world. We look at CIA-backed coups against governments which had nationalized a considerable amount of foreign investment. Using an event-study methodology, we find that private information regarding coup authorizations and planning increased the stock prices of expropriated multinationals that stood to benefit from the regime change. ***The presence of these abnormal returns suggests that there were leaks of classified information to asset traders.*** Consistent with theories of asset price determination under private information, this information often took some time to be fully reflected in the stock price. We find that coup authorizations, on net, contributed substantially more to stock price rises of highly exposed companies than the coup events themselves. >This suggests that most of the value of the coup to the affected companies had already been anticipated and incorporated into the asset price before the operation was undertaken.",
"title": ""
},
{
"docid": "459970",
"text": "I think to answer this question it is best for you to learn more about why people diversify through asset allocation. Look at related questions involving Asset Allocation here. I've asked a couple questions about asset allocation - I think you'll find the top rated answer on this post useful.",
"title": ""
},
{
"docid": "33764",
"text": "\"There is *some* merit to it, in that [federal gross receipts are largely uncorrelated with tax rates](https://i0.wp.com/wichitaliberty.org/wp-content/uploads/2014/02/top-federal-personal-income-tax-rates-tax-receipts-2014-02.png). There are two somewhat perverse consequences of that fact - First, raising taxes **doesn't** raise revenues, meaning we can't actually pay for \"\"moar free stuff from Uncle Sam!\"\" merely by adding an offsetting tax increase. And second, raising taxes on group-X (ie, the rich) to make them pay their \"\"fair\"\" share flat-out *doesn't work*, it's effectively just kicking them in the balls because we grudge them for having more money than we do. Now, as to whether or not lowering taxes really encourages companies to hire more and pay better - That's an entirely separate issue from whether or not it's revenue neutral from the perspective of the federal government. Fortunately, we have a recent historical example - Reagan did exactly that, which ushered in a period of corporate greed and erosion of workers' rights not seen since the end of the days of the Robber Barons. So on the front-end, Trump's not wrong; on the back end, he's trying to sell us unicorn farts.\"",
"title": ""
},
{
"docid": "315168",
"text": "Your house is not an asset, it is a liability. Assets feed you. Liabilites eat you. Robert Kiyosaki From a cash flow perspective your primary residence (ie your house) is an investment but it is not an asset. If you add up all the income your primary residence generates and subtract all the expenses it incurs, you will see why investment gurus claim this. Perform the same calculations for a rental property and you're more likely to find it has a positive cash flow. If it has a negative cash flow, it's not an asset either; it's a liability. A rental property with a negative cash flow is still an investment, but cash flow gurus will tell you it's a bad investment. While it is possible that your house may increase in value and you may be able to sell it for more than you paid, will you be able to sell it for more than all of the expenses incurred while living there? If so, you have an asset. Some people will purchase a home in need of repair, live in it and upgrade it, sell it for profit exceeding all expenses, and repeat. These people are flipping houses and generating capital gains based on their own hard work. In this instance a person's primary residence can be an asset. How much of an asset is calculated when the renovated house is sold.",
"title": ""
},
{
"docid": "15633",
"text": "\"There are loans. Usually they're secured by the assets, and you also cosign them personally. Your own credit worthiness comes to play, your own assets are in jeopardy. As to what it is that you're buying - no, it is not necessary for the seller to sell you the building. You might buy the business, but not the actual space it occupies. In fact, the space may not even belong to the seller. You may find yourself taking over the lease, which is in fact a liability, not an asset. You should agree with the seller on what exactly it is that you're buying. You should ask for a full inventory list that would include all the assets and the liabilities that would be transferred to you. Lease, as mentioned, but you might also \"\"buy\"\" loans, debts, lawsuits, and god knows what else that is attached to the business.\"",
"title": ""
},
{
"docid": "111091",
"text": "\"Unfortunately, there is very little data supporting fundamental analysis or technical analysis as appropriate tools to \"\"time\"\" the market. I will be so bold to say that technical analysis is meaningless. On the other hand, fundamental analysis has some merits. For example, the realization that CDOs were filled with toxic mortgages can be considered a product of fundamental analysis and hence provided traders with a directional assumption to buy CDSs. However, there is no way to tell when there is a good or bad time to buy or sell. The market behaves like a random 50/50 motion. There are many reasons for this and interestingly, there are many fundamentally sound companies that take large dips for no reason at all. Depending on your goal, you can either believe that this volatility will smooth over long periods and that the market has generally positive drift. On the other hand, I feel that the appropriate approach is to remain active. You will be able to mitigate the large downswings by simply staying small and diversifying - not in the sense of traditional finance but rather looking for uncorrelated products. Remember, volatility brings higher levels of correlation. My second suggestion is to look towards products like options to provide a method of shaping your P/L - giving up upside by selling calls against a long equity position is a great example. Ground your trades with fundamental beliefs if need be, but use your tools and knowledge to combat risks that may create long periods of drawdown.\"",
"title": ""
},
{
"docid": "139654",
"text": "The value of a company is, simplified, the sum of the value of the equity and the value of the debt. There are some other things to add/subtract to that, but just think about those for now. You could also say the value of a company is the value of its assets, or more precisely the value of the net cash flows those assets will generate in the future. So let's say you want to start a company, so you want to buy some assets. Maybe you want to buy a $200 asset. Well, you only have $100, so you take out a loan (debt) for $100 for the remainder. You buy the asset and start generating income. Let's say after a month you get bored and decide to sell the company. Let's assume the value of the assets hasn't changed. Your equity is worth $100, and you find a buyer who is willing to pay $100 for your company. Great! Right? Well there's still the $100 loan you owe, so you have to pay that back. And suddenly you now have $0. So in fact, you should have negotiated $200 with the buyer, because that's what the assets are actually worth. Then you can pay back the loan and still have the $100 in equity you deserve. (Alternatively, you could have negotiated the buyer to assume responsibility for the loan; same outcome for you.) Did that help?",
"title": ""
},
{
"docid": "104134",
"text": "\"You can move money from a 403b to a 401k plan, but the question you should ask yourself is whether it is a wise decision. Unless there are specific reasons for wanting to invest in your new employer's 401k (e.g. you can buy your employer's stock at discounted rates within the 401k, and this is a good investment according to your friends, neighbors, and brothers-in-law), you would be much better off moving the 403b money into an IRA, where you have many more choices for investment and usually can manage to find investments with lower investment costs (e.g. mutual fund fees) than in a typical employer's 401k plan. On the other hand, 401k assets are better protected than IRA assets in case you are sued and a court finds you to be liable for damages; the plaintiff cannot come after the 401k assets if you cannot pay. To answer the question of \"\"how?\"\", you need to talk to the HR people at your current employer to make sure that they are willing to accept a roll-over from another tax-deferred plan (not all plans are agreeable to do this) and get any paperwork from them, especially making sure that you find out where the check is to be sent, and to whom it should be payable. Then, talk to your previous employer's HR people and tell them that you want to roll over your 403b money into the 401k plan of your new employer, fill out the paperwork, make sure they know to whom to cut the check to, and where it is to be sent etc. In my personal experience, I was sent the check payable to the custodian of my new (IRA) account, and I had to send it on to the custodian; my 403b people refused to send the check directly to the new custodian. The following January, you will receive a 1099-R form from your 403b plan showing the amount transferred to the new custodian, with hopefully the correct code letter indicating that the money was rolled over into another tax-deferred account.\"",
"title": ""
},
{
"docid": "6245",
"text": "Your plan won't work. Working 40 hours a week at federal minimum wage (currently $7.25 / hr) for 52 weeks is an annual income of just over $15,000. Even assuming you can reliably get a return of 15% (which you definitely can't), you'd need to start with $100,000 of assets to earn this poverty income. Assuming a more reasonable 7% bumps the required assets up to over $200,000, and even then you're dead the first time you need to make withdrawals after a mistake or after a major market downturn. As a fellow math Ph.D. student, I know your pain. I, too, struggled for a while with boredom in an earlier career, but it's possible to make it work. I think the secret is to find a job that's engaging enough that your mind can't wander too much at work, and set aside some hobby time to work on interesting projects. You likely have some marketable skills that can work for you outside of academia, if you look for them, to allow you to find an interesting job. I think there's not much you can do besides trying not to get fired from your next McJob until you can find something more interesting. There's no magic money-for-nothing in the stock market.",
"title": ""
},
{
"docid": "18436",
"text": "Dollar cost averaging is an great way to diversify your investment risk. There's mainly 2 things you want to achieve when you're saving for retirement: 1) Keep your principal investment; 2) Grow it. The best methods recommended by most financial institutions are as follows: 1) Diversification; 2) Re-balance. There are a lot of additional recommendations, but these are my main take away. When you dollar cost average, you're essentially diversifying your exchange risk between the value of the funds you're investing. Including the ups and downs of the value of the underlying asset, may actually be re-balancing. Picking your asset portfolio: 1) You generally want to include within your 401k or any other invest, classes of investments that do not always move in total correlation as this allows you to diversify risk; 2) I'm making a lot of assumptions here - since you may have already picked your asset classes. Consider utilizing the following to tell you when to buy or sell your underlying investment: 1) Google re-balance excel sheet to find several examples of re-balance tools to help you always buy low and sell high; 2) Enter your portfolio investment; 3) Utilize the movement to invest in the underlying assets based on market movement; and 4) Execute in an emotionless way and stick to your plan. Example - Facts 1) I have 1 CAD and 1 USD in my 401k. Plan I will invest 1 dollar in the ratio of 50/50 - forever. Let's start in 2011 since we were closer to par: 2010 - 1 CAD (value 1 USD) and 1 USD (value 1 USD) = 50/50 ratio 2011 start - 1 CAD ( value .8 USD) and 1 USD (value 1 USD) = 40/60 ratio 2011 - rebalance - invest 1 USD as follows purchase .75 CAD (.60 USD) and purchase .40 USD = total of 1 USD reinvested 2011 end - 1.75 CAD (value 1.4USD) and 1.4 USD (value 1.4 USD) - 50/50 ratio As long as the fundamentals of your underlying assets (i.e. you're not expecting hyperinflation or your asset to approach 0), this approach will always build value over time since you're always buying low and selling high while dollar averaging. Keep in mind it does reduce your potential gains - but if you're looking to max gain, it may mean you're also max potential loss - unless you're able to find A symmetrical investments. I hope this helps.",
"title": ""
},
{
"docid": "266323",
"text": "The main advantage of commodities to a largely stock and bond portfolio is diversification and the main disadvantages are investment complexity and low long-term returns. Let's start with the advantage. Major commodities indices and the single commodities tend to be uncorrelated to stocks and bonds and will in general be diversifying especially over short periods. This relationship can be complex though as Supply can be even more complicated (think weather) so diversification may or may not work in your favor over long periods. However, trading in commodities can be very complex and expensive. Futures need to be rolled forward to keep an investment going. You really, really don't want to accidentally take delivery of 40000 pounds of cattle. Also, you need to properly take into account roll premiums (carry) when choosing the closing date for a future. This can be made easier by using commodities index ETFs but they can also have issues with rolling and generally have higher fees than stock index ETFs. Most importantly, it is worth understanding that the long-term return from commodities should be by definition (roughly) the inflation rate. With stocks and bonds you expect to make more than inflation over the long term. This is why many large institutions talk about commodities in their portfolio they often actually mean either short term tactical/algorithmic trading or long term investments in stocks closely tied to commodities production or processing. The two disadvantages above are why commodities are not recommended for most individual investors.",
"title": ""
},
{
"docid": "375253",
"text": "how do these margins vary over time Depends on a lot of factors. The bank's financial health, bank's ongoing business activities, profits generated from it's other businesses. If it is new to mortgages, it mightn't take a bigger margin to grow its business. If it is in the business for long, it might not be ready to tweak it down. If the housing market is down, they might lower their margin's to make lending attractive. If their competitors are lowering their margins, the bank in question might also. Do they rise when the base rate rises, or fall, or are they uncorrelated? When rates rise(money is being sucked out to curb spending), large amount of spending decreases. So you can imagine margins will need to decrease to keep the mortgage lending at previous levels. Would economic growth drive them up or down? Economic growth might make them go up. Like in case 1, base rates are low -> people are spending(chances are inflation will be high) -> margins will be higher(but real value of money will be dependent on inflation) Is there any kind of empirical or theoretical basis to guess at their movement? Get a basic text book on macroeconomics, the rates and inflation portion will be there. How the rates influence the money supply and all. It will much more sense. But the answer will encompass a mixture of all conditions and not a single one in isolation. So there isn't a definitive answer. This might give you an idea of how it works. It is for variable mortgage but should be more or less near to what you desire.",
"title": ""
},
{
"docid": "570855",
"text": "So wages for the working class are declining, young people can't find jobs and are over encumbered in school debt, unemployment is really high, yet these fools think they can find a sucker who can afford their overpriced assets? Good Luck.",
"title": ""
},
{
"docid": "279106",
"text": "I strongly suggest personal referral. Ask all of your friends/family/neighbors/co-workers/dog-sitter what they think of their brokers until you find someone who loves his broker. As for transferring assets, I've found it to be quite easy. It's in the new broker's best interest to get those assets, so he should be more than willing to help.",
"title": ""
},
{
"docid": "186575",
"text": "You're missing the concept of systemic risk, which is the risk of the entire market or an entire asset class. Diversification is about achieving a balance between risk and return that's appropriate for you. Your investment in Vanguard's fund, although diversified between many public companies, is still restricted to one asset class in one country. Yes, you lower your risk by investing in all of these companies, but you don't erase it entirely. Clearly, there is still risk, despite your diversification. You may decide that you want other investments or a different asset allocation that reduce the overall risk of your portfolio. Over the long run, you may earn a high level of return, but never forget that there is still risk involved. bonds seem pretty worthless, at least until I retire According to your profile, you're about my age. Our cohort will probably begin retiring sometime around 2050 or later, and no one knows what the bond market will look like over the next 40 years. We may have forecasts for the next few years, but not for almost four decades. Writing off an entire asset class for almost four decades doesn't seem like a good idea. Also, bonds are like equity, and all other asset classes, in that there are different levels of risk within the asset class too. When calculating the overall risk/return profile of my portfolio, I certainly don't consider Treasuries as the same risk level as corporate bonds or high-yield (or junk) bonds from abroad. Depending on your risk preferences, you may find that an asset allocation that includes US and/or international bonds/fixed-income, international equities, real-estate, and cash (to make rebalancing your asset allocation easier) reduces your risk to levels you're willing to tolerate, while still allowing you to achieve returns during periods where one asset class, e.g. equities, is losing value or performing below your expectations.",
"title": ""
}
] |
504
|
Healthy volunteers exhibit rapid and transient increase of cellular ATP after being bolus-injected with fructose.
|
[
{
"docid": "10883736",
"text": "CONTEXT The mechanisms that drive progression from fatty liver to steatohepatitis and cirrhosis are unknown. In animal models, obese mice with fatty livers are vulnerable to liver adenosine triphosphate (ATP) depletion and necrosis, suggesting that altered hepatic energy homeostasis may be involved. OBJECTIVE To determine if patients with fatty liver disease exhibit impaired recovery from hepatic ATP depletion. DESIGN Laboratory analysis of liver ATP stores monitored by nuclear magnetic resonance spectroscopy before and after transient hepatic ATP depletion was induced by fructose injection. The study was conducted between July 15 and August 30, 1998. SETTING University hospital. PATIENTS Eight consecutive adults with biopsy-proven nonalcoholic steatohepatitis and 7 healthy age- and sex-matched controls. MAIN OUTCOME MEASURE Level of ATP 1 hour after fructose infusion in patients vs controls. RESULTS In patients, serum aminotransferase levels were increased (P = .02 vs controls); albumin and bilirubin values were normal and clinical evidence of portal hypertension was absent in both groups. However, 2 patients had moderate fibrosis and 1 had cirrhosis on liver biopsy. Mean serum glucose, cholesterol, and triglyceride levels were similar between groups but patients weighed significantly more than controls (P = .02). Liver ATP levels were similar in the 2 groups before fructose infusion and decreased similarly in both after fructose infusion (P = .01 vs initial ATP levels). However, controls replenished their hepatic ATP stores during the 1-hour follow-up period (P<.02 vs minimum ATP) but patients did not. Hence, patients' hepatic ATP levels were lower than those of controls at the end of the study (P = .04). Body mass index (BMI) correlated inversely with ATP recovery, even in controls (R = -0.768; P = .07). Although BMI was greater in patients than controls (P = .02) and correlated strongly with fatty liver and serum aminotransferase elevations, neither of the latter 2 parameters nor the histologic severity of fibrosis strongly predicted hepatic ATP recovery. CONCLUSIONS These data suggest that recovery from hepatic ATP depletion becomes progressively less efficient as body mass increases in healthy controls and is severely impaired in patients with obesity-related nonalcoholic steatohepatitis.",
"title": "Alterations in liver ATP homeostasis in human nonalcoholic steatohepatitis: a pilot study."
}
] |
[
{
"docid": "38401028",
"text": "1. The changes in the metabolite content in freeze-clamped livers of fed rats occurring on perfusion with 10mm-d-fructose have been examined. 2. The most striking effects of fructose were an accumulation of fructose 1-phosphate, as already known, up to 8.7mumol/g of liver within 10min, a loss of total adenine nucleotides (up to 35% after 40min) with a decrease in the ATP content to 23% within 10min, a sevenfold rise in the concentration of IMP to 1.1mumol/g and an eightfold rise of alpha-glycerophosphate to 1.1mumol/g. 3. There was a transient decrease in P(i) from 4.2 to 1.7mumol/g. Within 40min the P(i) content recovered to the normal value, probably because of an uptake of P(i) from the perfusion medium. 4. The degradation of the adenine nucleotides beyond the stage of AMP can be accounted for by the decrease of ATP and P(i). As ATP inhibits 5-nucleotidase, and as P(i) inhibits AMP deaminase any AMP arising in the tissue is liable to undergo dephosphorylation or deamination under the conditions occurring after fructose loading. 5. The content of lactate increased to 4.3mumol/g at 80min; pyruvate also increased and the [lactate]/[pyruvate] ratio remained within physiological limits. 6. The concentration of free fructose within the liver remained much below that in the perfusion medium, indicating that the rate of penetration of fructose into the tissue was lower than the rate of utilization. 7. The fission of fructose 1-phosphate by liver aldolase is inhibited by several phosphorylated intermediates, especially by IMP. This inhibition is competitive with a K(i) of 0.1mm. 8. The maximal rates of the enzymes synthesizing and splitting fructose 1-phosphate are about equal. The accumulation of fructose 1-phosphate on fructose loading is due to the inhibition of the fission of fructose 1-phosphate by the IMP arising from the degradation of the adenine nucleotides.",
"title": "The cause of hepatic accumulation of fructose 1-phosphate on fructose loading."
},
{
"docid": "27550580",
"text": "OBJECTIVES The aim of this study was to determine the accuracy of the contrast \"bolus only\" T1 mapping cardiac magnetic resonance (CMR) technique for measuring myocardial extracellular volume fraction (ECV). BACKGROUND Myocardial ECV can be measured with T1 mapping before and after contrast agent if the contrast agent distribution between blood/myocardium is at equilibrium. Equilibrium distribution can be achieved with a primed contrast infusion (equilibrium contrast-CMR [EQ-CMR]) or might be approximated by the dynamic equilibration achieved by delayed post-bolus measurement. This bolus only approach is highly attractive, but currently limited data support its use. We compared the bolus only technique with 2 independent standards: collagen volume fraction (CVF) from myocardial biopsy in aortic stenosis (AS); and the infusion technique in 5 representative conditions. METHODS One hundred forty-seven subjects were studied: healthy volunteers (n = 50); hypertrophic cardiomyopathy (n = 25); severe AS (n = 22); amyloid (n = 20); and chronic myocardial infarction (n = 30). Bolus only (at 15 min) and infusion ECV measurements were performed and compared. In 18 subjects with severe AS the results were compared with histological CVF. RESULTS The ECV by both techniques correlated with histological CVF (n = 18, r² = 0.69, p < 0.01 vs. r² = 0.71, p < 0.01, p = 0.42 for comparison). Across health and disease, there was strong correlation between the techniques (r² = 0.97). However, in diseases of high ECV (amyloid, hypertrophic cardiomyopathy late gadolinium enhancement, and infarction), Bland-Altman analysis indicates the bolus only technique has a consistent and increasing offset, giving a higher value for ECVs above 0.4 (mean difference ± limit of agreement for ECV <0.4 = -0.004 ± 0.037 vs. ECV >0.4 = 0.040 ± 0.075, p < 0.001). CONCLUSIONS Bolus only, T1 mapping-derived ECV measurement is sufficient for ECV measurement across a range of cardiac diseases, and this approach is histologically validated in AS. However, when ECV is >0.4, the bolus only technique consistently measures ECV higher compared with infusion.",
"title": "T1 mapping for myocardial extracellular volume measurement by CMR: bolus only versus primed infusion technique."
},
{
"docid": "53211308",
"text": "BACKGROUND microRNAs (miRNAs) stably exist in circulating blood and are encapsulated in extracellular vesicles such as exosomes. The aims of this study were to identify which exosomal miRNAs are highly produced from epithelial ovarian cancer (EOC) cells, to analyze whether serum miRNA can be used to discriminate patients with EOC from healthy volunteers, and to investigate the functional role of exosomal miRNAs in ovarian cancer progression. METHODS Exosomes were collected from the culture media of serous ovarian cancer cell lines, namely TYK-nu and HeyA8 cells. An exosomal miRNA microarray revealed that several miRNAs including miR-99a-5p were specifically elevated in EOC-derived exosomes. Expression levels of serum miR-99a-5p in 62 patients with EOC, 26 patients with benign ovarian tumors, and 20 healthy volunteers were determined by miRNA quantitative reverse transcription-polymerase chain reaction. To investigate the role of exosomal miR-99a-5p in peritoneal dissemination, neighboring human peritoneal mesothelial cells (HPMCs) were treated with EOC-derived exosomes and then expression levels of miR-99a-5p were examined. Furthermore, mimics of miR-99a-5p were transfected into HPMCs and the effect of miR-99a-5p on cancer invasion was analyzed using a 3D culture model. Proteomic analysis with the tandem mass tag method was performed on HPMCs transfected with miR-99a-5p and then potential target genes of miR-99a-5p were examined. RESULTS The serum miR-99a-5p levels were significantly increased in patients with EOC, compared with those in benign tumor patients and healthy volunteers (1.7-fold and 2.8-fold, respectively). A receiver operating characteristic curve analysis showed with a cut-off of 1.41 showed sensitivity and specificity of 0.85 and 0.75, respectively, for detecting EOC (area under the curve = 0.88). Serum miR-99a-5p expression levels were significantly decreased after EOC surgeries (1.8 to 1.3, p = 0.002), indicating that miR-99a-5p reflects tumor burden. Treatment with EOC-derived exosomes significantly increased miR-99a-5p expression in HPMCs. HPMCs transfected with miR-99a-5p promoted ovarian cancer invasion and exhibited increased expression levels of fibronectin and vitronectin. CONCLUSIONS Serum miR-99a-5p is significantly elevated in ovarian cancer patients. Exosomal miR-99a-5p from EOC cells promotes cell invasion by affecting HPMCs through fibronectin and vitronectin upregulation and may serve as a target for inhibiting ovarian cancer progression.",
"title": "Exosomal miR-99a-5p is elevated in sera of ovarian cancer patients and promotes cancer cell invasion by increasing fibronectin and vitronectin expression in neighboring peritoneal mesothelial cells"
},
{
"docid": "21003930",
"text": "BACKGROUND Long-term exposure to pollution can lead to an increase in the rate of decline of lung function, especially in older individuals and in those with chronic obstructive pulmonary disease (COPD), whereas shorter-term exposure at higher pollution levels has been implicated in causing excess deaths from ischaemic heart disease and exacerbations of COPD. We aimed to assess the effects on respiratory and cardiovascular responses of walking down a busy street with high levels of pollution compared with walking in a traffic-free area with lower pollution levels in older adults. METHODS In this randomised, crossover study, we recruited men and women aged 60 years and older with angiographically proven stable ischaemic heart disease or stage 2 Global initiative for Obstructive Lung Disease (GOLD) COPD who had been clinically stable for 6 months, and age-matched healthy volunteers. Individuals with ischaemic heart disease or COPD were recruited from existing databases or outpatient respiratory and cardiology clinics at the Royal Brompton & Harefield NHS Foundation Trust and age-matched healthy volunteers using advertising and existing databases. All participants had abstained from smoking for at least 12 months and medications were taken as recommended by participants' doctors during the study. Participants were randomly assigned by drawing numbered disks at random from a bag to do a 2 h walk either along a commercial street in London (Oxford Street) or in an urban park (Hyde Park). Baseline measurements of participants were taken before the walk in the hospital laboratory. During each walk session, black carbon, particulate matter (PM) concentrations, ultrafine particles, and nitrogen dioxide (NO2) concentrations were measured. FINDINGS Between October, 2012, and June, 2014, we screened 135 participants, of whom 40 healthy volunteers, 40 individuals with COPD, and 39 with ischaemic heart disease were recruited. Concentrations of black carbon, NO2, PM10, PM2.5, and ultrafine particles were higher on Oxford Street than in Hyde Park. Participants with COPD reported more cough (odds ratio [OR] 1·95, 95% CI 0·96-3·95; p<0·1), sputum (3·15, 1·39-7·13; p<0·05), shortness of breath (1·86, 0·97-3·57; p<0·1), and wheeze (4·00, 1·52-10·50; p<0·05) after walking down Oxford Street compared with Hyde Park. In all participants, irrespective of their disease status, walking in Hyde Park led to an increase in lung function (forced expiratory volume in the first second [FEV1] and forced vital capacity [FVC]) and a decrease in pulse wave velocity (PWV) and augmentation index up to 26 h after the walk. By contrast, these beneficial responses were attenuated after walking on Oxford Street. In participants with COPD, a reduction in FEV1 and FVC, and an increase in R5-20 were associated with an increase in during-walk exposure to NO2, ultrafine particles and PM2.5, and an increase in PWV and augmentation index with NO2 and ultrafine particles. In healthy volunteers, PWV and augmentation index were associated both with black carbon and ultrafine particles. INTERPRETATION Short-term exposure to traffic pollution prevents the beneficial cardiopulmonary effects of walking in people with COPD, ischaemic heart disease, and those free from chronic cardiopulmonary diseases. Medication use might reduce the adverse effects of air pollution in individuals with ischaemic heart disease. Policies should aim to control ambient levels of air pollution along busy streets in view of these negative health effects. FUNDING British Heart Foundation.",
"title": "Respiratory and cardiovascular responses to walking down a traffic-polluted road compared with walking in a traffic-free area in participants aged 60 years and older with chronic lung or heart disease and age-matched healthy controls: a randomised, crossover study"
},
{
"docid": "2842550",
"text": "BACKGROUND Platelet deposition and aggregation are central to the pathogenesis of ischemic complications of acute coronary syndromes (ACS). Pharmacodynamic effects of the platelet glycoprotein IIb/IIIa antagonist eptifibatide have been delineated in healthy subjects but not in patients with ACS. We assessed effects of eptifibatide on ex vivo platelet aggregation in patients enrolled in the Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin (eptifibatide) Therapy (PURSUIT) trial of ACS. METHODS AND RESULTS Patients were randomly assigned to an intravenous bolus (180 microgram/kg) and 72-hour infusion of eptifibatide (2.0 microgram/kg per minute, n=48) or placebo (n=50). We assessed correlations of plasma eptifibatide levels with receptor occupancy and inhibition of ex vivo platelet aggregation at 5 minutes and 1, 4, 24, 48, and 72 hours during treatment and 4 and 8 hours after termination of infusion. Blood was collected in buffered citrate and D-phenylalanyl-L-prolyl-L-arginine chloromethylketone anticoagulants. Although eptifibatide produced profound, prolonged inhibition of platelet aggregation during therapy, aggregation appeared to recover partially by 4 hours after the bolus. The aggregation response was greater with thrombin receptor agonist peptide versus ADP stimulation; inhibition of platelet aggregation was greater in blood samples anticoagulated with citrate versus D-phenylalanyl-L-prolyl-L-arginine chloromethylketone (PPACK). Plasma eptifibatide levels correlated significantly with receptor occupancy but not with inhibition of platelet aggregation. CONCLUSIONS A bolus and infusion of eptifibatide inhibits platelet aggregation profoundly in patients with ACS and is followed by brief, partial recovery. These results enhance our understanding of the relation between pharmacodynamic and clinical effects of eptifibatide in such patients and may have important implications for its use in percutaneous interventions.",
"title": "Pharmacodynamics and pharmacokinetics of eptifibatide in patients with acute coronary syndromes: prospective analysis from PURSUIT."
},
{
"docid": "35766603",
"text": "PURPOSE To determine the toxicity and the therapeutic efficacy of the combination of the recombinant tumor necrosis factor alpha (rTNF alpha), recombinant interferon gamma (rIFN-gamma), and melphalan, we designed a protocol using isolation limb perfusion (ILP) with hyperthermia for in-transit metastases of melanoma and recurrent sarcoma. The triple combination was chosen because of the reported synergistic antitumor effect of rTNF alpha with IFN-gamma and of rTNF alpha with alkylating agents. PATIENTS AND METHODS Twenty-three patients received a total of 25 ILPs with the triple combination. There were 19 females and four males with either multiple progressive in-transit melanoma metastases of the extremities (stage IIIa or IIIab; 19 patients) or recurrent soft tissue sarcoma (five). The rTNF alpha was injected as a bolus in the arterial line, and total dose ranged between 2 and 4 mg, under hyperthermic conditions (40 degrees C to 40.5 degrees C) for 90 minutes. The rIFN-gamma was given subcutaneously (SC) on days -2 and -1 and in the perfusate, with rTNF alpha at the dose of 0.2 mg. Melphalan (Alkeran; Burroughs Wellcome Co, London, England) was administered in the perfusate at 40 micrograms/mL. RESULTS Toxicity observed during three ILPs in a pilot study with rTNF alpha included only two severe toxicities: one severe hypotension with tachycardia and transient oliguria and one moderate hypotension for 4 hours followed by severe kidney failure with complete recovery on day 29. In all 18 ILPs performed in the triple combination protocol, the patients received continuous infusion dopamine at 3 micrograms/kg/min from the start of ILP and for 72 hours and showed only mild hypotension and transient chills and temperature. Regional toxicity attributable to rTNF alpha was minimal. There have been 11 cases with hematologic toxicity consisting of neutropenia (one grade 4 and one grade 3) and neutropenia with thrombocytopenia (one grade 4 and three grade 2). Twelve patients had been previously treated with melphalan in ILP (11) or with cisplatin (one). The 23 patients are assessable: there have been 21 complete responses (CRs; range, 4 to 29 months; 89%), two partial responses (PRs; range, 2 to 3 months), and no failures. Overall disease-free survival and survival have been 70% and 76%, respectively, at 12 months. In all cases, softening of the nodules was obvious within 3 days after ILP and time to definite response ranged between day 5 and 30. CONCLUSION This preliminary analysis of a phase II study suggests that high-dose rTNF alpha can be administered with acceptable toxicity by ILP with dopamine and hyperhydration. Tumor responses can be evidenced in melanoma and sarcoma. Furthermore, combination of rTNF alpha, rIFN-gamma, and melphalan seems to achieve high efficacy with minimal toxicity, even after failure of prior therapy with melphalan alone.",
"title": "High-dose recombinant tumor necrosis factor alpha in combination with interferon gamma and melphalan in isolation perfusion of the limbs for melanoma and sarcoma."
},
{
"docid": "11868606",
"text": "Cystic Fibrosis (CF) is an inherited pleiotropic disease that results from abnormalities in the gene codes of a chloride channel. The lungs of CF patients are chronically infected by several pathogens but bacteraemia have rarely been reported in this pathology. Besides that, circulating monocytes in CF patients exhibit a patent Endotoxin Tolerance (ET) state since they show a significant reduction of the inflammatory response to bacterial stimulus. Despite a previous description of this phenomenon, the direct cause of ET in CF patients remains unknown. In this study we have researched the possible role of microbial/endotoxin translocation from a localized infection to the bloodstream as a potential cause of ET induction in CF patients. Plasma analysis of fourteen CF patients revealed high levels of LPS compared to healthy volunteers and patients who suffer from Chronic Obstructive Pulmonary Disease. Experiments in vitro showed that endotoxin concentrations found in plasma of CF patients were enough to induce an ET phenotype in monocytes from healthy controls. In agreement with clinical data, we failed to detect bacterial DNA in CF plasma. Our results suggest that soluble endotoxin present in bloodstream of CF patients causes endotoxin tolerance in their circulating monocytes.",
"title": "Translocated LPS Might Cause Endotoxin Tolerance in Circulating Monocytes of Cystic Fibrosis Patients"
},
{
"docid": "12903921",
"text": "It has been proved that oxidative stress increases when leukemia is accompanied by depression. This fact may indicate the role of oxidative stress in the development of depression in cancer patients. The aim of this study was to determine whether the acute myeloid leukemia of Brown Norway rats, which is accompanied by oxidative stress, evoked behavioral and receptor changes resembling alterations characteristic of rat models of depression. The rats were divided into two groups: leukemic rats and healthy control. Leukemia was induced through intraperitoneal injection of 10(7) promyelocytic leukemia cells to the Brown Norway rats. Depression-like behavior was evaluated in the forced swim test at 30 or 34 days after leukemic cells injection. The rats were killed after the evaluation and the spleen, brain cortex and hippocampus were excised. The red-ox state was assessed in homogenates of tissues by measuring total glutathione (GSH) content, the ferric ion reducing ability of plasma (FRAP) level, expression of heme oxygenase-1 (HO-1), biliverdin reductase (BvR) and ferritin mRNA, superoxide dismutase (SOD) activity, as well as malondialdehyde (MDA) concentration. Radioligand binding assay was used to assess of the effect of leukemia on cortical receptors. Leukemic cells were identified using RM-124 antibody by FACS Calibur flow cytometry. Leukemia influenced locomotory activity as well as forced swim test behavior in a 34-day series of experiments. Signs of oxidative stress in leukemic rats were observed in each examined stage of leukemia development. The FRAP values and glutathione contents, were significantly lowered whereas HO-1 mRNA expression, and malonodialdehyde concentrations were significantly increased in the spleen and brain structures of leukemic rats in comparison with the healthy controls. A significant increase in the potency of glycine to displace [(3)H]L-689,560 from the strychnine-insensitive glycine site of the N-methyl-D-aspartic (NMDA) receptors receptor complex in cortical homogenates of the leukemic rats in 30- and 34-day experimental series was observed in comparison with the control. Upregulation of 5-HT(2A) receptors was observed in rat cortex after 30 days of leukemia development but not in 34-days series compared with the control. It is concluded that disturbances in antioxidant system in brain cortex were accompanied by an activation of glycine sites of the NMDA receptor complex, regardless of stage of leukemia development, which are characteristic of model of depression. Findings of our study demonstrate the link between glutamatergic activity, oxidative stress and leukemia.",
"title": "Evaluation of oxidative status and depression-like responses in Brown Norway rats with acute myeloid leukemia"
},
{
"docid": "3083927",
"text": "We propose a model wherein chronic stress results in glucocorticoid receptor resistance (GCR) that, in turn, results in failure to down-regulate inflammatory response. Here we test the model in two viral-challenge studies. In study 1, we assessed stressful life events, GCR, and control variables including baseline antibody to the challenge virus, age, body mass index (BMI), season, race, sex, education, and virus type in 276 healthy adult volunteers. The volunteers were subsequently quarantined, exposed to one of two rhinoviruses, and followed for 5 d with nasal washes for viral isolation and assessment of signs/symptoms of a common cold. In study 2, we assessed the same control variables and GCR in 79 subjects who were subsequently exposed to a rhinovirus and monitored at baseline and for 5 d after viral challenge for the production of local (in nasal secretions) proinflammatory cytokines (IL-1β, TNF-α, and IL-6). Study 1: After covarying the control variables, those with recent exposure to a long-term threatening stressful experience demonstrated GCR; and those with GCR were at higher risk of subsequently developing a cold. Study 2: With the same controls used in study 1, greater GCR predicted the production of more local proinflammatory cytokines among infected subjects. These data provide support for a model suggesting that prolonged stressors result in GCR, which, in turn, interferes with appropriate regulation of inflammation. Because inflammation plays an important role in the onset and progression of a wide range of diseases, this model may have broad implications for understanding the role of stress in health.",
"title": "Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk."
},
{
"docid": "23036207",
"text": "Telomere extension has been proposed as a means to improve cell culture and tissue engineering and to treat disease. However, telomere extension by nonviral, nonintegrating methods remains inefficient. Here we report that delivery of modified mRNA encoding TERT to human fibroblasts and myoblasts increases telomerase activity transiently (24-48 h) and rapidly extends telomeres, after which telomeres resume shortening. Three successive transfections over a 4 d period extended telomeres up to 0.9 kb in a cell type-specific manner in fibroblasts and myoblasts and conferred an additional 28 ± 1.5 and 3.4 ± 0.4 population doublings (PDs), respectively. Proliferative capacity increased in a dose-dependent manner. The second and third transfections had less effect on proliferative capacity than the first, revealing a refractory period. However, the refractory period was transient as a later fourth transfection increased fibroblast proliferative capacity by an additional 15.2 ± 1.1 PDs, similar to the first transfection. Overall, these treatments led to an increase in absolute cell number of more than 10(12)-fold. Notably, unlike immortalized cells, all treated cell populations eventually stopped increasing in number and expressed senescence markers to the same extent as untreated cells. This rapid method of extending telomeres and increasing cell proliferative capacity without risk of insertional mutagenesis should have broad utility in disease modeling, drug screening, and regenerative medicine.",
"title": "Transient delivery of modified mRNA encoding TERT rapidly extends telomeres in human cells."
},
{
"docid": "6157371",
"text": "Actin and its key regulatory component, cofilin, are found together in large rod-shaped assemblies in neurons subjected to energy stress. Such inclusions are also enriched in Alzheimer's disease brain, and appear in transgenic models of neurodegeneration. Neuronal insults, such as energy loss and/or oxidative stress, result in rapid dephosphorylation of the cellular cofilin pool prior to its assembly into rod-shaped inclusions. Although these events implicate a role for phosphatases in cofilin rod formation, a mechanism linking energy stress, phosphocofilin turnover, and subsequent rod assembly has been elusive. We demonstrate the ATP-sensitive interaction of the cofilin phosphatase chronophin (CIN) with the chaperone hsp90 to form a biosensor that mediates cofilin/actin rod formation. Our results suggest a model whereby attenuated interactions between CIN and hsp90 during ATP depletion enhance CIN-dependent cofilin dephosphorylation and consequent rod assembly, thereby providing a mechanism for the formation of pathological actin/cofilin aggregates during neurodegenerative energy flux.",
"title": "Chronophin mediates an ATP-sensing mechanism for cofilin dephosphorylation and neuronal cofilin-actin rod formation."
},
{
"docid": "37562370",
"text": "OBJECTIVE The infrapatellar fat pad (IPFP) has been identified as a source of anterior knee pain. Fibrosis and marked inflammatory infiltrate in the IPFP of patients with arthritis of the knee and reduction in pain post knee replacement in patients following resection of the IPFP have been observed. We have investigated changes in the IPFP of rats undergoing the monoiodoacetate (MIA) model of degenerative joint disease, a model that exhibits some histopathological similarities to osteoarthritis (OA). METHODS Rats were injected intra-articularly with MIA and the development of weight bearing asymmetry was followed for 21 days as compared to vehicle-injected animals. In addition, IPFPs were removed from both ipsilateral and contralateral joints. Both inflammatory infiltrate and histopathological changes were analysed. RESULTS MIA injection caused marked weight bearing asymmetry. Ipsilateral IPFP wet weights were significantly increased on days 1 and 3 in MIA-treated animals. MIA treatment also resulted in significant increases in IPFP total white blood cells and monocytes on days 1, 3, and 7 and neutrophils on days 1 and 3. This was supported by histopathological findings at early time points which progressed to adipocyte necrosis, IPFP fibrosis, patellar cartilage and subchondral bone necrosis with synovial hyperplasia at later timepoints. CONCLUSIONS The current study clearly demonstrated that marked inflammatory changes in the IPFP occur during the early stage of the MIA model of OA which may contribute to the pain observed at this early stage. The role of the IPFP in later stages of the model needs to be further explored.",
"title": "Cellular and histopathological changes in the infrapatellar fat pad in the monoiodoacetate model of osteoarthritis pain."
},
{
"docid": "6108481",
"text": "It has been shown by several investigators that adipocyte number is stable in mature human beings and several species of rodents. Although the number of new cells appearing in the adipose depot can be measured histometrically and by Coulter counting of osmium-fixed cells, such methods do not distinguish between \"lipid filling\" of preexistent adipocytes and synthesis of new adipocytes. The experiments reported here using in vivo injection of [(3)H]thymidine show that synthesis of new adipocytes in the Sprague-Dawley rat continues after birth and ceases before sexual maturity. Furthermore, during the second and third postnatal weeks, a \"bed\" of preadipocytes is synthesized. Preadipocytes may take as long as 30 days to appear as mature adipocytes.",
"title": "Postnatal development of adipocyte cellularity in the normal rat."
},
{
"docid": "21053753",
"text": "The Constant-Murley shoulder assessment score has proven to be a valuable diagnostic instrument. Thus, in the literature it has been mentioned that the clinical accuracy of this score varies especially when comparing patients in larger, inhomogeneous patient groups. The \"relative Constant score\" (CS(rel)) tries to minimize these problems by using reference parameters out of healthy age and gender related control groups. The authors of this study tried to show that it is even more accurate to use the functional performance of the uninjured collateral shoulder of the same individual as reference, introducing the \"individual relative Constant score\" (CS(indiv)). The CS(indiv) and the CS(rel) were compared for 125 consecutive patients with shoulder disorders, and a group of 125 healthy volunteers as a control group. In a non-parametric comparison of the reciever operating characteristics the CS(indiv) shows the higher ability to discriminate between patients and healthy volunteers (p=0.004). This indicates that the individual relative Constant score gives a more accurate view about the functional result for shoulder disorders. It is expected to be more reliable for larger and incoherent patient populations, because specific interindividual differences, regarding the patient's age, gender and constitution are eliminated as well as other individual physiological parameters.",
"title": "Modification of the Constant-Murley shoulder score-introduction of the individual relative Constant score Individual shoulder assessment."
},
{
"docid": "39390206",
"text": "OBJECTIVE To measure in vivo, using diffusion tensor magnetic resonance imaging (DT-MRI) the extent of pathological damage of normal appearing brain tissue (NABT) from patients with migraine. METHODS Dual echo and DT-MRI scans of the brain were acquired from 34 patients with migraine and 17 sex and age matched healthy volunteers. Mean diffusivity (MD) and fractional anisotropy (FA) histograms of the NABT were obtained from all subjects and the histograms' peak heights and average NABT MD and FA measured. When present, average MD and FA values of T2 visible lesions were also measured. RESULTS In comparison with healthy volunteers, patients with migraine had lower MD histogram peak height (p=0.02) of the NABT. No differences were found in FA histogram derived metrics between migraine patients and healthy subjects. No difference was found for any MD and FA histogram derived metrics between migraine patients with and without brain MRI lesions, and between patients with and without aura. CONCLUSIONS This study shows that, although brain damage may extend beyond T2 weighted abnormalities in patients with migraine, the severity of these \"occult\" changes is mild compared with that found in other diseases associated with white matter abnormality.",
"title": "A diffusion tensor magnetic resonance imaging study of brain tissue from patients with migraine."
},
{
"docid": "3840043",
"text": "Cell types more advanced in development than embryonic stem cells, such as EpiSCs, fail to contribute to chimeras when injected into pre-implantation-stage blastocysts, apparently because the injected cells undergo apoptosis. Here we show that transient promotion of cell survival through expression of the anti-apoptotic gene BCL2 enables EpiSCs and Sox17+ endoderm progenitors to integrate into blastocysts and contribute to chimeric embryos. Upon injection into blastocyst, BCL2-expressing EpiSCs contributed to all bodily tissues in chimeric animals while Sox17+ endoderm progenitors specifically contributed in a region-specific fashion to endodermal tissues. In addition, BCL2 expression enabled rat EpiSCs to contribute to mouse embryonic chimeras, thereby forming interspecies chimeras that could survive to adulthood. Our system therefore provides a method to overcome cellular compatibility issues that typically restrict chimera formation. Application of this type of approach could broaden the use of embryonic chimeras, including region-specific chimeras, for basic developmental biology research and regenerative medicine.",
"title": "Inhibition of Apoptosis Overcomes Stage-Related Compatibility Barriers to Chimera Formation in Mouse Embryos."
},
{
"docid": "37969403",
"text": "New recombinant strains of attenuated Salmonella typhi used as live oral vaccines elicit potent immune responses. This study examined the patterns of cytokine production and proliferation to specific S. typhi antigens in subjects orally immunized with attenuated S. typhi vaccines CVD 906, CVD 908, and CVD 908 expressing the circumsporozoite protein of Plasmodium falciparum. After immunization, sensitized lymphocytes were found in subjects' blood that exhibited significantly increased proliferative responses and interferon-gamma production to purified S. typhi flagella when compared with preimmunization levels. Significant negative correlations were observed between interleukin-4 production and both interferon-gamma production and proliferation to S. typhi flagella. These results demonstrate that oral immunization with attenuated S. typhi strains alone or with those carrying a foreign gene elicits strong systemic cell-mediated immunity to purified S. typhi antigens, including the production of cytokines compatible with T1-type responses.",
"title": "Cytokine production patterns and lymphoproliferative responses in volunteers orally immunized with attenuated vaccine strains of Salmonella typhi."
},
{
"docid": "17973161",
"text": "Uncoupling protein 1 (UCP1) is highly expressed in brown adipose tissue, where it generates heat by uncoupling electron transport from ATP production. UCP1 is also found outside classical brown adipose tissue depots, in adipocytes that are termed 'brite' (brown-in-white) or 'beige'. In humans, the presence of brite or beige (brite/beige) adipocytes is correlated with a lean, metabolically healthy phenotype, but whether a causal relationship exists is not clear. Here we report that human brite/beige adipocyte progenitors proliferate in response to pro-angiogenic factors, in association with expanding capillary networks. Adipocytes formed from these progenitors transform in response to adenylate cyclase activation from being UCP1 negative to being UCP1 positive, which is a defining feature of the beige/brite phenotype, while displaying uncoupled respiration. When implanted into normal chow-fed, or into high-fat diet (HFD)-fed, glucose-intolerant NOD-scid IL2rg(null) (NSG) mice, brite/beige adipocytes activated in vitro enhance systemic glucose tolerance. These adipocytes express neuroendocrine and secreted factors, including the pro-protein convertase PCSK1, which is strongly associated with human obesity. Pro-angiogenic conditions therefore drive the proliferation of human beige/brite adipocyte progenitors, and activated beige/brite adipocytes can affect systemic glucose homeostasis, potentially through a neuroendocrine mechanism.",
"title": "Human ‘brite / beige’ adipocytes develop from capillary networks and their implantation improves metabolic homeostasis in mice"
},
{
"docid": "28845338",
"text": "One of the primary limitations of many psychiatric medications is weight gain, the mechanism of which remains to be fully elucidated. We conducted a 2-week double-blind placebo-controlled study on weight gain with olanzapine, which is frequently but unpredictably associated with this side effect, to address the possible mechanisms of weight gain independent of changes in the psychiatric condition for which it is prescribed. Healthy male volunteers were randomly assigned to olanzapine (5 mg/day for 7 days, then 10 mg/day for 7 days) or a matching placebo. Of the 24 participants, 19 completed the study (olanzapine, n=13; placebo, n=6). Body weight, glucose, triglyceride, total cholesterol, lipid, leptin, insulin, and aldosterone levels, resting metabolic rate, body composition, physical activity, and 24-h dietary intake were assessed. A significant increase in weight as well as triglyceride, insulin, and leptin levels were found in the olanzapine group as a whole. In participants receiving olanzapine who actually gained weight (n=8), lean but not fat mass increased, as did insulin, fasting glucose, total cholesterol, low-density lipoprotein, and non-high-density lipoprotein levels, whereas aldosterone levels decreased. There were no significant metabolic or endocrine changes in participants receiving placebo or in those receiving olanzapine who did not gain weight. Early metabolic changes appear to be independent of accumulation of fat.",
"title": "Increased lean body mass as an early indicator of olanzapine-induced weight gain in healthy men."
},
{
"docid": "26045237",
"text": "BACKGROUND Transthyretin amyloidosis is caused by the deposition of hepatocyte-derived transthyretin amyloid in peripheral nerves and the heart. A therapeutic approach mediated by RNA interference (RNAi) could reduce the production of transthyretin. METHODS We identified a potent antitransthyretin small interfering RNA, which was encapsulated in two distinct first- and second-generation formulations of lipid nanoparticles, generating ALN-TTR01 and ALN-TTR02, respectively. Each formulation was studied in a single-dose, placebo-controlled phase 1 trial to assess safety and effect on transthyretin levels. We first evaluated ALN-TTR01 (at doses of 0.01 to 1.0 mg per kilogram of body weight) in 32 patients with transthyretin amyloidosis and then evaluated ALN-TTR02 (at doses of 0.01 to 0.5 mg per kilogram) in 17 healthy volunteers. RESULTS Rapid, dose-dependent, and durable lowering of transthyretin levels was observed in the two trials. At a dose of 1.0 mg per kilogram, ALN-TTR01 suppressed transthyretin, with a mean reduction at day 7 of 38%, as compared with placebo (P=0.01); levels of mutant and nonmutant forms of transthyretin were lowered to a similar extent. For ALN-TTR02, the mean reductions in transthyretin levels at doses of 0.15 to 0.3 mg per kilogram ranged from 82.3 to 86.8%, with reductions of 56.6 to 67.1% at 28 days (P<0.001 for all comparisons). These reductions were shown to be RNAi-mediated. Mild-to-moderate infusion-related reactions occurred in 20.8% and 7.7% of participants receiving ALN-TTR01 and ALN-TTR02, respectively. CONCLUSIONS ALN-TTR01 and ALN-TTR02 suppressed the production of both mutant and nonmutant forms of transthyretin, establishing proof of concept for RNAi therapy targeting messenger RNA transcribed from a disease-causing gene. (Funded by Alnylam Pharmaceuticals; ClinicalTrials.gov numbers, NCT01148953 and NCT01559077.).",
"title": "Safety and efficacy of RNAi therapy for transthyretin amyloidosis."
},
{
"docid": "13380011",
"text": "Partial inhibition of mitochondrial respiratory complex I by rotenone reproduces aspects of Parkinson's disease in rodents. The hypothesis that rotenone enhancement of neuronal cell death is attributable to oxidative stress was tested in an acute glutamate excitotoxicity model using primary cultures of rat cerebellar granule neurons. As little as 5 nM rotenone increased mitochondrial superoxide (O2*-) levels and potentiated glutamate-induced cytoplasmic Ca2+ deregulation, the first irreversible stage of necrotic cell death. However, the potent cell-permeant O2*- trap manganese tetrakis (N-ethylpyridinium-2yl) porphyrin failed to prevent the effects of the inhibitor. The bioenergetic consequences of rotenone addition were quantified by monitoring cell respiration. Glutamate activation of NMDA receptors used the full respiratory capacity of the in situ mitochondria, and >80% of the glutamate-stimulated respiration was attributable to increased cellular ATP demand. Rotenone at 20 nM inhibited basal and carbonyl cyanide p-trifluoromethoxyphenylhydrazone-stimulated cell respiration and caused respiratory failure in the presence of glutamate. ATP synthase inhibition by oligomycin was also toxic in the presence of glutamate. We conclude that the cell vulnerability in the rotenone model of partial complex I deficiency under these specific conditions is primarily determined by spare respiratory capacity rather than oxidative stress.",
"title": "Spare respiratory capacity rather than oxidative stress regulates glutamate excitotoxicity after partial respiratory inhibition of mitochondrial complex I with rotenone."
},
{
"docid": "9831859",
"text": "Pancreatic stellate cells (PSC) produce the stromal reaction in pancreatic cancer, but their role in cancer progression is not fully elucidated. We examined the influence of PSCs on pancreatic cancer growth using (a) an orthotopic model of pancreatic cancer and (b) cultured human PSCs (hPSC) and human pancreatic cancer cell lines MiaPaCa-2 and Panc-1. Athymic mice received an intrapancreatic injection of saline, hPSCs, MiaPaCa-2 cells, or hPSCs + MiaPaCa-2. After 7 weeks, tumor size, metastases, and tumor histology were assessed. In vitro studies assessed the effect of cancer cell secretions on PSC migration and the effect of hPSC secretions on cancer cell proliferation, apoptosis, and migration. Possible mediators of the effects of hPSC secretions on cancer cell proliferation were examined using neutralizing antibodies. Compared with mice receiving MiaPaCa-2 cells alone, mice injected with hPSCs + MiaPaCa-2 exhibited (a) increased tumor size and regional and distant metastasis, (b) fibrotic bands (desmoplasia) containing activated PSCs within tumors, and (c) increased tumor cell numbers. In vitro studies showed that, in the presence of pancreatic cancer cells, PSC migration was significantly increased. Furthermore, hPSC secretions induced the proliferation and migration, but inhibited the apoptosis, of MiaPaCa-2 and Panc-1 cells. The proliferative effect of hPSC secretions on pancreatic cancer cells was inhibited in the presence of neutralizing antibody to platelet-derived growth factor. Our studies indicate a significant interaction between pancreatic cancer cells and stromal cells (PSCs) and imply that pancreatic cancer cells recruit stromal cells to establish an environment that promotes cancer progression.",
"title": "Pancreatic stellate cells: partners in crime with pancreatic cancer cells."
},
{
"docid": "23273454",
"text": "Eleven mammalian toll-like receptors (TLRs 1-11) have been identified to date and are known to play a crucial role in the regulation of immune responses; however, the factors that regulate TLR expression and function in vivo are poorly understood. Therefore, in the present study, we investigated the physiological regulation of TLR expression and function in humans. To examine the influence of diurnal rhythmicity on TLR expression and function, peripheral venous blood samples were collected from healthy volunteers (n = 8) at time points coinciding with the peak and nadir in the endogenous circulating cortisol concentration. While no diurnal rhythmicity in the expression of TLRs 1, 2, 4 or 9 was observed, the upregulation of costimulatory (CD80 and CD86) and antigen-presenting (MHC class II) molecules on CD14(+) monocytes following activation with specific TLR ligands was greater (P < 0.05) in samples obtained in the evening compared with the morning. To examine the influence of physical stress on TLR expression and function, peripheral venous blood samples were collected from healthy volunteers (n = 11) at rest and following 1.5 h of strenuous exercise in the heat (34 degrees C). Strenuous exercise resulted in a decrease (P < 0.005) in the expression of TLRs 1, 2 and 4 on CD14(+) monocytes. Furthermore, the upregulation of CD80, CD86, MHC class II and interleukin-6 by CD14(+) monocytes following activation with specific TLR ligands was decreased (P < 0.05) in samples obtained following exercise compared with at rest. These results demonstrate that TLR function is subject to modulation under physiological conditions in vivo and provide evidence for the role of immunomodulatory hormones in the regulation of TLR function.",
"title": "The physiological regulation of toll-like receptor expression and function in humans."
},
{
"docid": "9629682",
"text": "The field of macro-imaging has grown considerably with the appearance of innovative clearing methods and confocal microscopes with lasers capable of penetrating increasing tissue depths. The ability to visualize and model the growth of whole organs as they develop from birth, or with manipulation, disease or injury, provides new ways of thinking about development, tissue-wide signaling, and cell-to-cell interactions. The zebrafish (Danio rerio) has ascended from a predominantly developmental model to a leading adult model of tissue regeneration. The unmatched neurogenic and regenerative capacity of the mature central nervous system, in particular, has received much attention, however tools to interrogate the adult brain are sparse. At present there exists no straightforward methods of visualizing changes in the whole adult brain in 3-dimensions (3-D) to examine systemic patterns of cell proliferation or cell populations of interest under physiological, injury, or diseased conditions. The method presented here is the first of its kind to offer an efficient step-by-step pipeline from intraperitoneal injections of the proliferative marker, 5-ethynyl-2'-deoxyuridine (EdU), to whole brain labeling, to a final embedded and cleared brain sample suitable for 3-D imaging using optical projection tomography (OPT). Moreover, this method allows potential for imaging GFP-reporter lines and cell-specific antibodies in the presence or absence of EdU. The small size of the adult zebrafish brain, the highly consistent degree of EdU labeling, and the use of basic clearing agents, benzyl benzoate, and benzyl alcohol, makes this method highly tractable for most laboratories interested in understanding the vertebrate central nervous system in health and disease. Post-processing of OPT-imaged adult zebrafish brains injected with EdU illustrate that proliferative patterns in EdU can readily be observed and analyzed using IMARIS and/or FIJI/IMAGEJ software. This protocol will be a valuable tool to unlock new ways of understanding systemic patterns in cell proliferation in the healthy and injured brain, brain-wide cellular interactions, stem cell niche development, and changes in brain morphology.",
"title": "A Whole Brain Staining, Embedding, and Clearing Pipeline for Adult Zebrafish to Visualize Cell Proliferation and Morphology in 3-Dimensions"
},
{
"docid": "27910499",
"text": "Delayed T cell recovery and restricted T cell receptor (TCR) diversity after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are associated with increased risks of infection and cancer relapse. Technical challenges have limited faithful measurement of TCR diversity after allo-HSCT. Here we combined 5' rapid amplification of complementary DNA ends PCR with deep sequencing to quantify TCR diversity in 28 recipients of allo-HSCT using a single oligonucleotide pair. Analysis of duplicate blood samples confirmed that we accurately determined the frequency of individual TCRs. After 6 months, cord blood-graft recipients approximated the TCR diversity of healthy individuals, whereas recipients of T cell-depleted peripheral-blood stem cell grafts had 28-fold and 14-fold lower CD4(+) and CD8(+) T cell diversities, respectively. After 12 months, these deficiencies had improved for the CD4(+) but not the CD8(+) T cell compartment. Overall, this method provides unprecedented views of T cell repertoire recovery after allo-HSCT and may identify patients at high risk of infection or relapse.",
"title": "Quantitative assessment of T-cell repertoire recovery after hematopoietic stem cell transplantation"
},
{
"docid": "6372244",
"text": "Antibiotics can have significant and long-lasting effects on the gastrointestinal tract microbiota, reducing colonization resistance against pathogens including Clostridium difficile. Here we show that antibiotic treatment induces substantial changes in the gut microbial community and in the metabolome of mice susceptible to C. difficile infection. Levels of secondary bile acids, glucose, free fatty acids and dipeptides decrease, whereas those of primary bile acids and sugar alcohols increase, reflecting the modified metabolic activity of the altered gut microbiome. In vitro and ex vivo analyses demonstrate that C. difficile can exploit specific metabolites that become more abundant in the mouse gut after antibiotics, including the primary bile acid taurocholate for germination, and carbon sources such as mannitol, fructose, sorbitol, raffinose and stachyose for growth. Our results indicate that antibiotic-mediated alteration of the gut microbiome converts the global metabolic profile to one that favours C. difficile germination and growth.",
"title": "Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection"
},
{
"docid": "37362689",
"text": "The bulk of ATP consumed by various cellular processes in higher eukaryotes is normally produced by five multimeric protein complexes (I-V) embedded within the inner mitochondrial membrane, in a process known as oxidative phosphorylation (OXPHOS). Maintenance of energy homeostasis under most physiological conditions is therefore contingent upon the ability of OXPHOS to meet cellular changes in bioenergetic demand, with a chronic failure to do so being a frequent cause of human disease. With the exception of Complex II, the structural subunits of OXPHOS complexes are encoded by both the nuclear and the mitochondrial genomes. The physical separation of the two genomes necessitates that the expression of the 13 mitochondrially encoded polypeptides be co-ordinated with that of relevant nuclear-encoded partners in order to assemble functional holoenzyme complexes. Complex biogenesis is a highly ordered process, and several nuclear-encoded factors that function at distinct stages in the assembly of individual OXPHOS complexes have been identified.",
"title": "Oxidative phosphorylation: synthesis of mitochondrially encoded proteins and assembly of individual structural subunits into functional holoenzyme complexes."
},
{
"docid": "35520219",
"text": "Unilateral injection of kainic acid (KA) into the dorsal hippocampus of adult mice induces spontaneous recurrent partial seizures and replicates histopathological changes observed in human mesial temporal lobe epilepsy (MTLE) (Bouilleret V et al., Neuroscience 1999; 89:717-729). Alterations in pre- and postsynaptic components of GABAergic neurotransmission were investigated immunohistochemically at different time points (1-120 days) in this mouse model of MTLE. Markers of GABAergic interneurons (parvalbumin, calbindin-D28k, and calretinin), the type-1 GABA transporter (GAT1), and major GABA(A)-receptor subunits expressed in the hippocampal formation were analyzed. Acutely, KA injection produced a profound loss of hilar cells but only limited damage to CA1 and CA3 pyramidal cells. In addition, parvalbumin and calbindin-D28k staining of interneurons disappeared irreversibly in CA1 and dentate gyrus (DG), whereas calretinin staining was spared. The prominent GABA(A)-receptor alpha1 subunit staining of interneurons also disappeared after KA treatment, suggesting acute degeneration of these cells. Likewise, GAT1 immunoreactivity revealed degenerating terminals at 24 h post-KA in CA1 and DC and subsided almost completely thereafter. Loss of CA1 and, to a lesser extent, CA3 neurons became evident at 7-15 days post-KA. It was more accentuated after 1 month, accompanied by a corresponding reduction of GABA(A)-receptor staining. In contrast, DC granule cells were markedly enlarged and dispersed in the molecular layer and exhibited a prominent increase in GABA(A)-receptor subunit staining. After 4 months, the dorsal CA1 area was lost almost entirely, CA3 was reduced, and the DG represented most of the remaining dorsal hippocampal formation. No significant morphological alterations were detected contralaterally. These results suggest that loss of hilar cells and GABAergic neurons contributes to epileptogenesis in this model of MTLE. In contrast, long-term degeneration of pyramidal cells and granule cell dispersion may reflect distinct responses to recurrent seizures. Finally, GABA(A)-receptor upregulation in the DG may represent a compensatory response persisting for several months in epileptic mice.",
"title": "Early loss of interneurons and delayed subunit-specific changes in GABA(A)-receptor expression in a mouse model of mesial temporal lobe epilepsy."
},
{
"docid": "38886345",
"text": "BACKGROUND JX-594 is a targeted oncolytic poxvirus designed to selectively replicate in and destroy cancer cells with cell-cycle abnormalities and epidermal growth factor receptor (EGFR)-ras pathway activation. Direct oncolysis plus granulocyte-macrophage colony-stimulating factor (GM-CSF) expression also stimulates shutdown of tumour vasculature and antitumoral immunity. We aimed to assess intratumoral injection of JX-594 in patients with refractory primary or metastatic liver cancer. METHODS Between Jan 4, 2006, and July 4, 2007, 14 patients with histologically confirmed refractory primary or metastatic liver tumours (up to 10.9 cm total diameter) that were amenable to image-guided intratumoral injections were enrolled into this non-comparative, open-label, phase I dose-escalation trial (standard 3x3 design; two to six patients for each dose with 12-18 estimated total patients). Patients received one of four doses of intratumoral JX-594 (10(8) plaque-forming units [pfu], 3x10(8) pfu, 10(9) pfu, or 3x10(9) pfu) every 3 weeks at Dong-A University Hospital (Busan, South Korea). Patients were monitored after treatment for at least 48 h in hospital and for at least 4 weeks as out-patients. Adverse event-monitoring according to the National Cancer Institute Common Toxicity Criteria (version 3) and standard laboratory toxicity grading for haematology, liver and renal function, coagulation studies, serum chemistry, and urinalysis were done. The primary aims were to ascertain the maximum-tolerated dose (MTD) and safety of JX-594 treatment. Data were also collected on pharmacokinetics, pharmacodynamics, and efficacy. Analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00629759. FINDINGS Of 22 patients with liver tumours who were assessed for eligibility, eight patients did not meet inclusion criteria. Therefore, 14 patients, including those with hepatocellular, colorectal, melanoma, and lung cancer, were enrolled. Patients were heavily pretreated (5.6 previous treatments, SD 2.8, range 2.0-12.0) and had large tumours (7.0 cm diameter, SD 2.7, range 1.8-10.9). Patients received a mean of 3.4 (SD 2.2, range 1.0-8.0) cycles of JX-594. All patients were evaluable for toxicity. All patients experienced grade I-III flu-like symptoms, and four had transient grade I-III dose-related thrombocytopenia. Grade III hyperbilirubinaemia was dose-limiting in both patients at the highest dose; the MTD was therefore 1x10(9) pfu. JX-594 replication-dependent dissemination in blood was shown, with resultant infection of non-injected tumour sites. GM-CSF expression resulted in grade I-III increases in neutrophil counts in four of six patients at the MTD. Tumour responses were shown in injected and non-injected tumours. Ten patients were radiographically evaluable for objective responses; non-evaluable patients had contraindications to contrast medium (n=2) or no post-treatment scans (n=2). According to Response Evaluation Criteria in Solid Tumors (RECIST), three patients had partial response, six had stable disease, and one had progressive disease. INTERPRETATION Intratumoral injection of JX-594 into primary or metastatic liver tumours was generally well-tolerated. Direct hyperbilirubinaemia was the dose-limiting toxicity. Safety was acceptable in the context of JX-594 replication, GM-CSF expression, systemic dissemination, and JX-594 had anti-tumoral effects against several refractory carcinomas. Phase II trials are now underway.",
"title": "Use of a targeted oncolytic poxvirus, JX-594, in patients with refractory primary or metastatic liver cancer: a phase I trial."
},
{
"docid": "27077180",
"text": "The large Trp gene family encodes transient receptor potential (TRP) proteins that form novel cation-selective ion channels. In mammals, 28 Trp channel genes have been identified. TRP proteins exhibit diverse permeation and gating properties and are involved in a plethora of physiologic functions with a strong impact on cellular sensing and signaling pathways. Indeed, mutations in human genes encoding TRP channels, the so-called \"TRP channelopathies,\" are responsible for a number of hereditary diseases that affect the musculoskeletal, cardiovascular, genitourinary, and nervous systems. This review gives an overview of the functional properties of mammalian TRP channels, describes their roles in acquired and hereditary diseases, and discusses their potential as drug targets for therapeutic intervention.",
"title": "Transient receptor potential channels as drug targets: from the science of basic research to the art of medicine."
}
] |
PLAIN-3460
|
Why is Meat a Risk Factor for Diabetes?
|
[
{
"docid": "MED-3302",
"text": "In November 2007 a novel neuropathy, immune-mediated polyradiculoneuropathy (IP), was identified among workers at a Minnesota swine abattoir where a unique compressed air technique was used to remove porcine brains. An epidemiologic investigation at another abattoir in Indiana that also uses this process was launched to evaluate workers self-reporting neurologic illness compatible with IP. A nested case-control study was performed to identify cases and risk factors. Six confirmed, one probable, and three possible IP cases were detected. IP cases were 28-52 years old, of Latino origin, and 62.5% female. Onset dates ranged from April 2005-December 2007; 60% were hospitalized. IP cases at this plant were similar in clinical presentation and exposure risks to those detected in Minnesota. Swine abattoirs using similar brain extraction methods should discontinue this process.",
"title": "A clustering of immune-mediated polyradiculoneuropathy among swine abattoir workers exposed to aerosolized porcine brains, Indiana, United States."
},
{
"docid": "MED-2123",
"text": "Milk has been recognized to represent a functionally active nutrient system promoting neonatal growth of mammals. Cell growth is regulated by the nutrient-sensitive kinase mechanistic target of rapamycin complex 1 (mTORC1). There is still a lack of information on the mechanisms of mTORC1 up-regulation by milk consumption. This review presents milk as a materno-neonatal relay system functioning by transfer of preferential amino acids, which increase plasma levels of glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), insulin, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) for mTORC1 activation. Importantly, milk exosomes, which regularly contain microRNA-21, most likely represent a genetic transfection system enhancing mTORC1-driven metabolic processes. Whereas human breast milk is the ideal food for infants allowing appropriate postnatal growth and species-specific metabolic programming, persistent high milk signaling during adolescence and adulthood by continued cow´s milk consumption may promote mTORC1-driven diseases of civilization.",
"title": "Milk is not just food but most likely a genetic transfection system activating mTORC1 signaling for postnatal growth"
},
{
"docid": "MED-1796",
"text": "Background Several studies have shown that Adenovirus 36 (Ad36) influences the risk of obesity in humans. Clarifying the relationship between Ad36 infection and obesity could lead to more effective approaches for the management of obesity. The objective of this study was to conduct a meta-analysis to confirm the influence of Ad36 infection on obesity and metabolic markers. Methodology/Principal Findings We searched MEDLINE and the Cochrane Library for pertinent articles (including their references) published between 1951 and April 22, 2012. Only English language reports of original observational studies were included in this meta-analysis. Data extraction was performed independently by two reviewers. Weighted mean differences (WMDs) and pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated using the random effects model. Of 237 potentially relevant studies, 10 cross-sectional studies (n = 2,870) conformed to the selection criteria. Pooled analysis showed that the WMD for BMI of Ad36 infection compared with non-infection was 3.19 (95% CI 1.44–4.93; P<0.001). Sensitivity analysis restricted to studies of adults yielded a similar result of 3.18 (95% CI 0.78–5.57; P = 0.009). The increased risk of obesity associated with Ad36 infection was also significant (OR: 1.9; 95% CI: 1.01–3.56; P = 0.047). No significant differences were found in relation to total cholesterol (P = 0.83), triglycerides (P = 0.64), HDL (P = 0.69), blood glucose (P = 0.08), waist circumstance (P = 0.09), and systolic blood pressure (P = 0.25). Conclusion/Significance Ad36 infection was associated with the risk of obesity and weight gain, but was not associated with abnormal metabolic markers including waist circumstance. It suggests that Ad36 infection is more associated with accumulation of subcutaneous fat than that of visceral fat. The relationship between Ad36 and obesity should be assessed by further studies, including well-designed prospective studies, to gain a better understanding of whether Ad36 plays a role in the etiology of human obesity.",
"title": "Association of Adenovirus 36 Infection with Obesity and Metabolic Markers in Humans: A Meta-Analysis of Observational Studies"
},
{
"docid": "MED-1802",
"text": "Hypotheses regarding the role of meat consumption in body weight modulation are contradictory. Prospective studies on an association between meat consumption and BMI change are limited. We assessed the association between meat consumption and change in BMI over time in 3902 men and women aged 55-69 y from the Netherlands Cohort Study. Dietary intake was estimated at baseline using a FFQ. BMI was ascertained through baseline self-reported height (1986) and weight (1986, 1992, and 2000). Analyses were based on sex-specific categories of daily total fresh meat, red meat, beef, pork, minced meat, chicken, processed meat, and fish consumption at baseline. Linear mixed effect modeling adjusted for confounders was used to assess longitudinal associations. Significant cross-sectional differences in BMI between quintiles of total meat intake were observed (P-trend < 0.01; both sexes). No association between total fresh meat consumption and prospective BMI change was observed in men (BMI change highest vs. lowest quintile after 14 y: -0.06 kg/m²; P = 0.75) and women (BMI change: 0.26 kg/m²; P = 0.20). Men with the highest intake of beef experienced a significantly lower increase in BMI after 6 and 14 y than those with the lowest intake (BMI change after 14 y 0.60 kg/m²). After 14 y, a significantly higher increase in BMI was associated with higher intakes of pork in women (BMI change highest vs. lowest quintile: 0.47 kg/m²) and chicken in both sexes (BMI change highest vs. lowest category in both men and women: 0.36 kg/m²). The results remained similar when stratifying on median baseline BMI, and age-stratified analyses yielded mixed results. Differential BMI change effects were observed for several subtypes of meat. However, total meat consumption, or factors directly related to total meat intake, was not strongly associated with weight change during the 14-y prospective follow-up in this elderly population.",
"title": "Longitudinal changes in BMI in older adults are associated with meat consumption differentially, by type of meat consumed."
},
{
"docid": "MED-2120",
"text": "In a recent study, prostatectomy specimens from which Propionibacterium acnes was cultured were more likely to have inflammation than culture-negative specimens or specimens positive for other bacteria, leading the authors to hypothesize that P. acnes-mediated inflammation may contribute to prostate carcinogenesis. To indirectly explore associations between P. acnes and prostate cancer, we investigated severe acne, as measured by tetracycline use for four or more years, in relation to incident prostate cancer in the Health Professionals Follow-up Study. On the 1992 follow-up questionnaire, participants were asked whether they had ever used “tetracycline for at least two months at a time (e.g., for acne or other reason)” and their duration of use. Prostate cancer diagnoses were ascertained on each subsequent biennial questionnaire and confirmed by medical record review. Between 1992 and 2002, 2,147 cases of prostate cancer were reported among 34,629 eligible participants. Men who used tetracycline for four or more years had a significantly higher risk of prostate cancer (16 cases, 1,569 person-years) than men who did not use tetracycline (2,071 cases, 304,822 person-years, multivariable-adjusted RR=1.70, 95% CI:1.03–2.80). Although intriguing, this finding should be viewed cautiously because of the small number of exposed cases, indirect assessment of severe acne, and complex etiology of acne, which is not limited to P. acnes infection. Therefore, additional biologic and epidemiologic studies are necessary to determine and elucidate the possible role of P. acnes infection in prostate carcinogenesis.",
"title": "ACNE AND RISK OF PROSTATE CANCER"
},
{
"docid": "MED-3308",
"text": "An occupational health survey conducted in a workshop in which asbestos cement was used showed initial atmospheric asbestos levels ranging from 1.9 to 27.5 fibres per millilitre of air. Radiological changes suggestive of asbestos-related pleural disease were found in 2 workers (2.5%), while 3 (3.8%) had borderline features of asbestosis. The survey confirmed that uncontrolled and hazardous use of asbestos continues in industry despite public awareness of its dangers and the Asbestos Regulations of 1987.",
"title": "Third wave of asbestos-related disease from secondary use of asbestos. A case report from industry."
},
{
"docid": "MED-3294",
"text": "In the past two decades or so, a number of viruses have emerged in the global swine population. Some, such as porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2), cause economically important diseases in pigs, whereas others such as porcine torque teno virus (TTV), now known as Torque teno sus virus (TTSuV), porcine bocavirus (PBoV) and related novel parvoviruses, porcine kobuvirus, porcine toroviruses (PToV) and porcine lymphotropic herpesviruses (PLHV), are mostly subclinical in swine herds. Although some emerging swine viruses such as swine hepatitis E virus (swine HEV), porcine endogenous retrovirus (PERV) and porcine sapovirus (porcine SaV) may have a limited clinical implication in swine health, they do pose a potential public health concern in humans due to zoonotic (swine HEV) or potential zoonotic (porcine SaV) and xenozoonotic (PERV, PLHV) risks. Other emerging viruses such as Nipah virus, Bungowannah virus and Menangle virus not only cause diseases in pigs but some also pose important zoonotic threat to humans. This article focuses on emerging and re-emerging swine viruses that have a limited or uncertain clinical and economic impact on pig health. The transmission, epidemiology and pathogenic potential of these viruses are discussed. In addition, the two economically important emerging viruses, PRRSV and PCV2, are also briefly discussed to identify important knowledge gaps. © 2012 Blackwell Verlag GmbH.",
"title": "Emerging and re-emerging swine viruses."
},
{
"docid": "MED-5238",
"text": "The prevalence of diabetes and obesity has increased rapidly over the last few decades in both developed and developing countries. While it is intuitively appealing to suggest that lifestyle risk factors such as decreased physical activity and adoption of poor diets can explain much of the increase, the evidence to support this is poor. Given this, there has been an impetus to look more widely than traditional lifestyle and biomedical risk factors, especially those risk factors, which arise from the environment. Since the industrial revolution, there has been an introduction of many chemicals into our environment, which have now become environmental pollutants. There has been growing interest in one key class of environmental pollutants known as persistent organic pollutants (POPs) and their potential role in the development of diabetes. This review will summarise and appraise the current epidemiological evidence relating POPs to diabetes and highlight gaps and flaws in this evidence. Copyright © 2013 Elsevier Masson SAS. All rights reserved.",
"title": "Persistent organic pollutants and diabetes: a review of the epidemiological evidence."
},
{
"docid": "MED-3288",
"text": "In the fall of 2007, the Minnesota Department of Health was notified of 11 cases of an unexplained neurological illness, all linked to a pork processing plant, Quality Pork Processors, Inc., in Austin, MN. The cluster of workers had been experiencing similar symptoms, including fatigue, pain, numbness, and tingling in their extremities as well as weakness. The symptoms were described as more sensory than motor, and all patients had evidence of polyradiculoneuropathy with signs of nerve root irritation. An epidemiological investigation revealed that the only commonality between cases was their exposure to a pork brain extraction procedure involving compressed air. As relatives of the cases remained asymptomatic and all cultures for known pathogens were negative, the etiology of the syndrome seemed not to be infectious. Clinically, the syndrome was most akin to chronic inflammatory demyelinating polyneuropathy. Laboratory tests corroborated the clinical findings, revealing inflammation of peripheral nerves and nerve roots; however, these cases also had features clinically distinct from chronic inflammatory demyelinating polyneuropathy as well as laboratory testing revealing a novel immunoglobulin G immunostaining pattern. This suggested that the observed inflammation was the result of 1 or more unidentified antigens. This syndrome was ultimately dubbed progressive inflammatory neuropathy and was theorized to be an autoimmune reaction to aerosolized porcine neural tissue. Since the investigation's outset, 18 cases of progressive inflammatory neuropathy have been identified at the Minnesota pork processing plant, with 5 similar cases at an Indiana plant and 1 case at a Nebraskan plant. The plants in which cases have been identified have since stopped the use of compressed air in removing pork brains. All cases have stabilized or improved, with some requiring immunosuppressive and analgesic treatment. The study of progressive inflammatory neuropathy is ongoing, and the details of this investigation highlight the value of epidemiological principles in the identification and containment of outbreaks while researchers attempt to uncover the unique pathophysiology and potential etiology of the illness. Mt Sinai J Med 76:442-447, 2009. (c) 2009 Mount Sinai School of Medicine.",
"title": "Outbreak of progressive inflammatory neuropathy following exposure to aerosolized porcine neural tissue."
},
{
"docid": "MED-1807",
"text": "BACKGROUND: As protein is considered to increase thermogenesis and satiety more than other macronutrients, it may have beneficial effects on prevention of weight gain and weight maintenance. OBJECTIVE: The objective of this study is to assess the association between the amount and type of dietary protein, and subsequent changes in weight and waist circumference (WC). METHODS: 89,432 men and women from five countries participating in European Prospective Investigation into Cancer and Nutrition (EPIC) were followed for a mean of 6.5 years. Associations between the intake of protein or subgroups of protein (from animal and plant sources) and changes in weight (g per year) or WC (cm per year) were investigated using gender and centre-specific multiple regression analyses. Adjustments were made for other baseline dietary factors, baseline anthropometrics, demographic and lifestyle factors and follow-up time. We used random effect meta-analyses to obtain pooled estimates across centres. RESULTS: Higher intake of total protein, and protein from animal sources was associated with subsequent weight gain for both genders, strongest among women, and the association was mainly attributable to protein from red and processed meat and poultry rather than from fish and dairy sources. There was no overall association between intake of plant protein and subsequent changes in weight. No clear overall associations between intakes of total protein or any of the subgroups and changes in WC were present. The associations showed some heterogeneity between centres, but pooling of estimates was still considered justified. CONCLUSION: A high intake of protein was not found associated with lower weight or waist gain in this observational study. In contrast, protein from food items of animal origin, especially meat and poultry, seemed to be positively associated with long-term weight gain. There were no clear associations for waist changes.",
"title": "Intake of total, animal and plant protein and subsequent changes in weight or waist circumference in European men and women: the Diogenes project."
},
{
"docid": "MED-2126",
"text": "Increased protein supply by feeding cow-milk-based infant formula in comparison to lower protein content of human milk is a well-recognized major risk factor of childhood obesity. However, there is yet no conclusive biochemical concept explaining the mechanisms of formula-induced childhood obesity. It is the intention of this article to provide the biochemical link between leucine-mediated signalling of mammalian milk proteins and adipogenesis as well as early adipogenic programming. Leucine has been identified as the predominant signal transducer of mammalian milk, which stimulates the nutrient-sensitive kinase mammalian target of rapamycin complex 1 (mTORC1). Leucine thus functions as a maternal-neonatal relay for mTORC1-dependent neonatal β-cell proliferation and insulin secretion. The mTORC1 target S6K1 plays a pivotal role in stimulation of mesenchymal stem cells to differentiate into adipocytes and to induce insulin resistance. It is of most critical concern that infant formulas provide higher amounts of leucine in comparison to human milk. Exaggerated leucine-mediated mTORC1-S6K1 signalling induced by infant formulas may thus explain increased adipogenesis and generation of lifelong elevated adipocyte numbers. Attenuation of mTORC1 signalling of infant formula by leucine restriction to physiologic lower levels of human milk offers a great chance for the prevention of childhood obesity and obesity-related metabolic diseases.",
"title": "Excessive Leucine-mTORC1-Signalling of Cow Milk-Based Infant Formula: The Missing Link to Understand Early Childhood Obesity"
},
{
"docid": "MED-2510",
"text": "Dietary restriction (DR) extends the lifespan of a wide range of species, although the universality of this effect has never been quantitatively examined. Here, we report the first comprehensive comparative meta-analysis of DR across studies and species. Overall, DR significantly increased lifespan, but this effect is modulated by several factors. In general, DR has less effect in extending lifespan in males and also in non-model organisms. Surprisingly, the proportion of protein intake was more important for life extension via DR than the degree of caloric restriction. Furthermore, we show that reduction in both age-dependent and age-independent mortality rates drives life extension by DR among the well-studied laboratory model species (yeast, nematode worms, fruit flies and rodents). Our results suggest that convergent adaptation to laboratory conditions better explains the observed DR-longevity relationship than evolutionary conservation although alternative explanations are possible. © 2012 The Authors. Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.",
"title": "Comparative and meta-analytic insights into life extension via dietary restriction."
},
{
"docid": "MED-2121",
"text": "The purpose of this paper is to highlight the endocrine signaling of Western diet, a fundamental environmental factor involved in the pathogenesis of epidemic acne. Western nutrition is characterized by high calorie uptake, high glycemic load, high fat and meat intake, as well as increased consumption of insulin- and IGF-1-level elevating dairy proteins. Metabolic signals of Western diet are sensed by the nutrient-sensitive kinase, mammalian target of rapamycin complex 1 (mTORC1), which integrates signals of cellular energy, growth factors (insulin, IGF-1) and protein-derived signals, predominantly leucine, provided in high amounts by milk proteins and meat. mTORC1 activates SREBP, the master transcription factor of lipogenesis. Leucine stimulates mTORC1-SREBP signaling and leucine is directly converted by sebocytes into fatty acids and sterols for sebaceous lipid synthesis. Over-activated mTORC1 increases androgen hormone secretion and most likely amplifies androgen-driven mTORC1 signaling of sebaceous follicles. Testosterone directly activates mTORC1. Future research should investigate the effects of isotretinoin on sebocyte mTORC1 activity. It is conceivable that isotretinoin may downregulate mTORC1 in sebocytes by upregulation of nuclear levels of FoxO1. The role of Western diet in acne can only be fully appreciated when all stimulatory inputs for maximal mTORC1 activation, i.e., glucose, insulin, IGF-1 and leucine, are adequately considered. Epidemic acne has to be recognized as an mTORC1-driven disease of civilization like obesity, type 2 diabetes, cancer and neurodegenerative diseases. These new insights into Western diet-mediated mTORC1-hyperactivity provide a rational basis for dietary intervention in acne by attenuating mTORC1 signaling by reducing (1) total energy intake, (2) hyperglycemic carbohydrates, (3) insulinotropic dairy proteins and (4) leucine-rich meat and dairy proteins. The necessary dietary changes are opposed to the evolution of industrialized food and fast food distribution of Westernized countries. An attenuation of mTORC1 signaling is only possible by increasing the consumption of vegetables and fruit, the major components of vegan or Paleolithic diets. The dermatologist bears a tremendous responsibility for his young acne patients who should be advised to modify their dietary habits in order to reduce activating stimuli of mTORC1, not only to improve acne but to prevent the harmful and expensive march to other mTORC1-related chronic diseases later in life.",
"title": "Dietary intervention in acne"
},
{
"docid": "MED-1804",
"text": "There is increasing evidence that obesity in humans is associated with infection with human adenovirus-36 (Adv36). Infection of experimental animals with Adv36 demonstrates that this virus causes obesity. Human studies have shown a prevalence of Adv36 infection of 30% or greater in obese adult humans, but a correlation with obesity has not always been demonstrated. In contrast, three published studies and one presented study with a total of 559 children all show that there is an increase in prevalence of Adv36 infection in obese children (28%) compared to non-obese children (10%). The explanation for the apparently more robust correlation of Adv36 infection with obesity in children vs. adults is not clear. The data in animals and people suggests that Adv36 has contributed to the worldwide increase in childhood obesity. More research is needed to identify prevalences and consequences of Adv36 infection in people of all age groups and geographic locations.",
"title": "Human adenovirus-36 and childhood obesity."
},
{
"docid": "MED-1436",
"text": "PURPOSE OF REVIEW: Sirtuins are a family of enzymes highly conserved in evolution and involved in mechanisms known to promote healthy ageing and longevity. This review aims to discuss recent advances in understanding the role of sirtuins, in particular mammalian SIRT1, in promoting longevity and its potential molecular basis for neuroprotection against cognitive ageing and Alzheimer's disease pathology. RECENT FINDINGS: Accumulative increase in oxidative stress during ageing has been shown to decrease SIRT1 activity in catabolic tissue, possibly by direct inactivation by reactive oxygen. SIRT1 overexpression prevents oxidative stress-induced apoptosis and increases resistance to oxidative stress through regulation of the FOXO family of forkhead transcription factors. In addition, resveratrol strongly stimulates SIRT1 deacetylase activity in a dose-dependent manner by increasing its binding affinity to both the acetylated substrate and NAD(+). Recently, SIRT1 has been shown to affect amyloid production through its influence over the ADAM10 gene. Upregulation of SIRT1 can also induce the Notch pathway and inhibit mTOR signalling. SUMMARY: Recent studies have revealed some of the mechanisms and pathways that are associated with the neuroprotective effects of SIRT1.",
"title": "Sirtuins in cognitive ageing and Alzheimer's disease."
},
{
"docid": "MED-4896",
"text": "BACKGROUND: In westernized societies, acne vulgaris is a nearly universal skin disease afflicting 79% to 95% of the adolescent population. In men and women older than 25 years, 40% to 54% have some degree of facial acne, and clinical facial acne persists into middle age in 12% of women and 3% of men. Epidemiological evidence suggests that acne incidence rates are considerably lower in nonwesternized societies. Herein we report the prevalence of acne in 2 nonwesternized populations: the Kitavan Islanders of Papua New Guinea and the Aché hunter-gatherers of Paraguay. Additionally, we analyze how elements in nonwesternized environments may influence the development of acne. OBSERVATIONS: Of 1200 Kitavan subjects examined (including 300 aged 15-25 years), no case of acne (grade 1 with multiple comedones or grades 2-4) was observed. Of 115 Aché subjects examined (including 15 aged 15-25 years) over 843 days, no case of active acne (grades 1-4) was observed. CONCLUSIONS: The astonishing difference in acne incidence rates between nonwesternized and fully modernized societies cannot be solely attributed to genetic differences among populations but likely results from differing environmental factors. Identification of these factors may be useful in the treatment of acne in Western populations.",
"title": "Acne vulgaris: a disease of Western civilization."
},
{
"docid": "MED-2124",
"text": "Acne appears to represent a visible indicator disease of over-activated mTORC1 signalling, an unfavour-able metabolic deviation on the road to serious common Western diseases of civilisation associated with increased body mass index and insulin resistance. Exaggerated mTORC1 signalling by Western diet explains the association of acne with increased body mass index, insulin resistance, and early onset of menarche. Both, a high glycaemic load and increased consumption of milk and milk products, staples of Western diet, aggravate mammalian target of rapamycin complex 1 signalling. This review of the literature summarises present evidence for an association between acne, increased body mass index, insulin resistance and Western diet. By dietary intervention with a Palaeolithic-type diet, the dermatologist has the chance to attenuate patients' increased mTORC1 signalling by reducing glycaemic load and milk consumption, which may not only improve acne but may delay the march to more serious mTORC1-driven diseases of civilisation.",
"title": "Acne: risk indicator for increased body mass index and insulin resistance."
},
{
"docid": "MED-3318",
"text": "Smoking is an established risk factor for pancreatic cancer; however, detailed examination of the association of smoking intensity, smoking duration, and cumulative smoking dose with pancreatic cancer is limited. The authors analyzed pooled data from the international Pancreatic Cancer Cohort Consortium nested case-control study (1,481 cases, 1,539 controls). Odds ratios and 95% confidence intervals were calculated by using unconditional logistic regression. Smoking intensity effects were examined with an excess odds ratio model that was linear in pack-years and exponential in cigarettes smoked per day and its square. When compared with never smokers, current smokers had a significantly elevated risk (odds ratio (OR) = 1.77, 95% confidence interval (CI): 1.38, 2.26). Risk increased significantly with greater intensity (≥30 cigarettes/day: OR = 1.75, 95% CI: 1.27, 2.42), duration (≥50 years: OR = 2.13, 95% CI: 1.25, 3.62), and cumulative smoking dose (≥40 pack-years: OR = 1.78, 95% CI: 1.35, 2.34). Risk more than 15 years after smoking cessation was similar to that for never smokers. Estimates of excess odds ratio per pack-year declined with increasing intensity, suggesting greater risk for total exposure delivered at lower intensity for longer duration than for higher intensity for shorter duration. This finding and the decline in risk after smoking cessation suggest that smoking has a late-stage effect on pancreatic carcinogenesis.",
"title": "Cigarette Smoking and Pancreatic Cancer: A Pooled Analysis From the Pancreatic Cancer Cohort Consortium"
},
{
"docid": "MED-3317",
"text": "Twenty-four patients, all of whom were exposed to aerosolized porcine brain tissue through work-place environment (abattoir), developed a syndrome of immune-mediated polyradiculoneuropathy; three also had central nervous system manifestations (transverse myelitis, meningoencephalitis, and aseptic meningitis). Patients had characteristic electrophysiological findings of very distal and proximal conduction slowing (prolonged distal and F-wave latencies, regions where the blood-nerve barrier is the most permeable) and all patients' serum contained a novel IgG immunofluorescence pattern. Nerve pathology, when available, showed mild changes of segmental demyelination, axonal degeneration, and inflammatory changes. Patients had meaningful improvement of symptoms and electrophysiologic findings with immune therapy and with removal of exposure to aerosolized brain tissue. We postulate that this outbreak is an auto-immune polyradiculoneuropathy triggered by occupational exposure to multiple aerosolized porcine neural tissue antigens that result in neural damage where the blood-nerve barrier is the least robust. © 2011 Peripheral Nerve Society.",
"title": "Auto-immune polyradiculoneuropathy and a novel IgG biomarker in workers exposed to aerosolized porcine brain."
},
{
"docid": "MED-2396",
"text": "Rates of type 2 diabetes mellitus (T2DM), both in the United States and worldwide, have been rising at an alarming rate over the last two decades. Because this disease is viewed as primarily being attributable to unhealthy lifestyle habits, a great deal of emphasis has been placed on encouraging increased exercise, better dietary habits, and weight loss. Recent studies reveal that the presence of several persistent organic pollutants (POPs) can confer greater risk for developing the disease than some of the established lifestyle risk factors. In fact, evidence suggests the hypothesis that obesity might only be a significant risk factor when adipose tissue contains high amounts of POPs. Chlorinated pesticides and polychlorinated biphenyls, in particular, have been strongly linked to the development of metabolic syndrome, insulin resistance, and T2DM. In addition to reviewing the evidence associating POPs to these conditions, this article explores the possible contribution of farmed Atlantic salmon - a significant and common dietary source of POPs - with blood sugar dysregulation conditions.",
"title": "The role of persistent organic pollutants in the worldwide epidemic of type 2 diabetes mellitus and the possible connection to Farmed Atlantic Salm..."
},
{
"docid": "MED-1799",
"text": "Human adenovirus Ad-36 is causatively and correlatively linked with animal and human obesity, respectively. Ad-36 enhances differentiation of rodent preadipocytes, but its effect on adipogenesis in humans is unknown. To indirectly assess the role of Ad-36-induced adipogenesis in human obesity, the effect of the virus on commitment, differentiation, and lipid accumulation was investigated in vitro in primary human adipose-derived stem/stromal cells (hASC). Ad-36 infected hASC in a time- and dose-dependent manner. Even in the presence of osteogenic media, Ad-36-infected hASC showed significantly greater lipid accumulation, suggestive of their commitment to the adipocyte lineage. Even in the absence of adipogenic inducers, Ad-36 significantly increased hASC differentiation, as indicated by a time-dependent expression of genes within the adipogenic cascade—CCAAT/Enhancer binding protein-β, peroxisome proliferator-activated receptor-γ, and fatty acid-binding protein—and consequentially increased lipid accumulation in a time- and viral dose-dependent manner. Induction of hASC to the adipocyte state by Ad-36 was further supported by increased expression of lipoprotein lipase and the accumulation of its extracellular fraction. hASC from subjects harboring Ad-36 DNA in their adipose tissue due to natural infection had significantly greater ability to differentiate compared with Ad-36 DNA-negative counterparts, which offers a proof of concept. Thus, Ad-36 has the potential to induce adipogenesis in hASC, which may contribute to adiposity induced by the virus.",
"title": "Adipogenic Human Adenovirus Ad-36 Induces Commitment, Differentiation, and Lipid Accumulation in Human Adipose-Derived Stem Cells"
},
{
"docid": "MED-2389",
"text": "Background: Prospective data regarding persistent organic pollutants (POPs) and risk of type 2 diabetes (T2D) are limited, and the results for individual POPs are not entirely consistent across studies. Objectives: We prospectively examined plasma POP concentrations in relation to incident T2D and summarized existing evidence in a meta-analysis. Methods: Plasma polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyldichloroethylene (DDE), and hexachlorobenzene (HCB) concentrations were measured in 1,095 women who were free of diabetes at blood draw in 1989–1990 and participated in two case–control studies in the Nurses’ Health Study. We identified 48 incident T2D cases through 30 June 2008. We conducted a literature search in PubMed and EMBASE through December 2011 to identify prospective studies on POPs in relation to diabetes. We used a fixed-effects model to summarize results. Results: After multivariable adjustment, plasma HCB concentration was positively associated with incident T2D [pooled odds ratio (OR) 3.59 (95% CI: 1.49, 8.64, ptrend = 0.003) comparing extreme tertiles]. Other POPs were not significantly associated with diabetes. After pooling our results with those of six published prospective studies that included 842 diabetes cases in total, we found that HCB and total PCBs both were associated with diabetes: the pooled ORs were 2.00 (95% CI: 1.13, 3.53; I2 = 21.4%, pheterogeneity = 0.28) and 1.70 (95% CI: 1.28, 2.27; I2 = 16.3%, pheterogeneity = 0.30) for HCB and total PCBs, respectively. Conclusions: These findings support an association between POP exposure and the risk of T2D.",
"title": "Persistent Organic Pollutants and Type 2 Diabetes: A Prospective Analysis in the Nurses’ Health Study and Meta-analysis"
},
{
"docid": "MED-2136",
"text": "Prostate cancer (PCa) is dependent on androgen receptor signaling and aberrations of the PI3K-Akt-mTORC1 pathway mediating excessive and sustained growth signaling. The nutrient-sensitive kinase mTORC1 is upregulated in nearly 100% of advanced human PCas. Oncogenic mTORC1 signaling activates key subsets of mRNAs that cooperate in distinct steps of PCa initiation and progression. Epidemiological evidence points to increased dairy protein consumption as a major dietary risk factor for the development of PCa. mTORC1 is a master regulator of protein synthesis, lipid synthesis and autophagy pathways that couple nutrient sensing to cell growth and cancer. This review provides evidence that PCa initiation and progression are promoted by cow´s milk, but not human milk, stimulation of mTORC1 signaling. Mammalian milk is presented as an endocrine signaling system, which activates mTORC1, promotes cell growth and proliferation and suppresses autophagy. Naturally, milk-mediated mTORC1 signaling is restricted only to the postnatal growth phase of mammals. However, persistent consumption of cow´s milk proteins in humans provide highly insulinotropic branched-chain amino acids (BCAAs) provided by milk´s fast hydrolysable whey proteins, which elevate postprandial plasma insulin levels, and increase hepatic IGF-1 plasma concentrations by casein-derived amino acids. BCAAs, insulin and IGF-1 are pivotal activating signals of mTORC1. Increased cow´s milk protein-mediated mTORC1 signaling along with constant exposure to commercial cow´s milk estrogens derived from pregnant cows may explain the observed association between high dairy consumption and increased risk of PCa in Westernized societies. As well-balanced mTORC1-signaling plays an important role in appropriate prostate morphogenesis and differentiation, exaggerated mTORC1-signaling by high cow´s milk consumption predominantly during critical growth phases of prostate development and differentiation may exert long-term adverse effects on prostate health. Attenuation of mTORC1 signaling by contemporary Paleolithic diets and restriction of dairy protein intake, especially during mTORC1-dependent phases of prostate development and differentiation, may offer protection from the most common dairy-promoted cancer in men of Western societies.",
"title": "The impact of cow's milk-mediated mTORC1-signaling in the initiation and progression of prostate cancer"
},
{
"docid": "MED-2137",
"text": "Common cancer is an age-related disease. Slow aging is associated with reduced and delayed carcinogenesis. Calorie restriction (CR), the most studied anti-aging intervention, prevents cancer by slowing down the aging process. Evidence is emerging that CR decelerates aging by deactivating MTOR (Target of Rapamycin). Rapamycin and other rapalogs suppress cellular senescence, slow down aging and postpone age-related diseases including cancer. At the same time, rapalogs are approved for certain cancer treatments. Can cancer prevention be explained by direct targeting of cancer cells? Or does rapamycin prevent cancer indirectly through slowing down the aging process? Increasing evidence points to the latter scenario.",
"title": "Rapalogs in cancer prevention"
},
{
"docid": "MED-2394",
"text": "Background One of the outcomes positively associated with dioxin exposure in humans is type 2 diabetes. Objectives This study was conducted in order to find the molecular biological evidence for the diabetogenic action of dioxin in adipose samples from Vietnam veterans. Methods We obtained 313 adipose tissue samples both from Vietnam veterans who were exposed to dioxin (Operation Ranch Hand) and from comparison veterans who served in Southeast Asia with no record of dioxin exposure. We conducted quantitative reverse-transcribed polymerase chain reaction studies on selected marker mRNAs from these samples. Results We found the most sensitive and reliable molecular indicator of dioxin-induced diabetes to be the ratio of mRNA of glucose transporter 4 (GLUT4) and nuclear transcription factor kappa B (NFκB), a marker of inflammation. This ratio showed significant correlations to serum dioxin residues and to fasting glucose among those in the Ranch Hand group and, surprisingly, even in the comparison group, who have low levels of dioxin comparable to the general public. Such a correlation in the comparison group was particularly significant among those with known risk factors such as obesity and family history of diabetes. Conclusions These results show that the GLUT4:NFκB ratio is a reliable marker for the diabetogenic action of dioxin, particularly at very low exposure levels that are not much higher than those found in the general public, implying a need to address current exposure levels.",
"title": "Molecular Epidemiologic Evidence for Diabetogenic Effects of Dioxin Exposure in U.S. Air Force Veterans of the Vietnam War"
},
{
"docid": "MED-1801",
"text": "OBJECTIVE: In 1976, the Royal College of Physicians and the British Cardiac Society recommended eating less fatty red meat and more poultry instead because it was lean. However, the situation has changed since that time, with a striking increase in fat content of the standard broiler chicken. The aim of the present study was to report a snapshot of data on fat in chickens now sold to the public. DESIGN: Samples were obtained randomly between 2004 and 2008 from UK supermarkets, farm shops and a football club. The amount of chicken fat was estimated by emulsification and chloroform/methanol extraction. SETTING: Food sold in supermarkets and farms in England. SUBJECTS: Chicken samples. RESULTS: The fat energy exceeded that of protein. There has been a loss of n-3 fatty acids. The n-6:n-3 ratio was found to be as high as 9:1, as opposed to the recommendation of about 2:1. Moreover, the TAG level in the meat and whole bird mostly exceeded the proportion of phospholipids, which should be the higher for muscle function. The n-3 fatty acid docosapentaenoic acid (DPA, 22 : 5n-3) was in excess of DHA (22 : 6n-3). Previous analyses had, as usual for birds, more DHA than DPA. CONCLUSIONS: Traditional poultry and eggs were one of the few land-based sources of long-chain n-3 fatty acids, especially DHA, which is synthesized from its parent precursor in the green food chain. In view of the obesity epidemic, chickens that provide several times the fat energy compared with protein seem illogical. This type of chicken husbandry needs to be reviewed with regard to its implications for animal welfare and human nutrition.",
"title": "Modern organic and broiler chickens sold for human consumption provide more energy from fat than protein."
},
{
"docid": "MED-2402",
"text": "Despite a proposed protective effect of fish intake on the risk of cardiovascular disease, epidemiologic evidence on fish intake and mortality is inconsistent. We investigated associations of fish intake, assessed through a validated food frequency questionnaire, with risks of total and cause-specific mortality in 2 prospective cohort studies of 134,296 Chinese men and women (1997–2009). Vital status and date and cause of death were ascertained through annual linkage to the Shanghai Vital Statistics Registry database and biennial home visits. Cox regression was used to calculate hazard ratios and corresponding 95% confidence intervals. After excluding the first year of observation, the analysis included 3,666 deaths among women and 2,170 deaths among men. Fish intake was inversely associated with risks of total, ischemic stroke, and diabetes mortality; the corresponding hazard ratios for the highest quintiles of intake compared with the lowest were 0.84 (95% confidence interval (CI): 0.76, 0.92), 0.63 (95% CI: 0.41, 0.94), and 0.61 (95% CI: 0.39, 0.95), respectively. No associations with cancer or ischemic heart disease mortality were observed. Further analyses suggested that the inverse associations with total, ischemic stroke, and diabetes mortality were primarily related to consumption of saltwater fish and intake of long-chain n-3 fatty acids. Overall, our findings support the postulated health benefits of fish consumption.",
"title": "Fish Intake and Risks of Total and Cause-specific Mortality in 2 Population-based Cohort Studies of 134,296 Men and Women"
},
{
"docid": "MED-2498",
"text": "Dietary restriction (DR) and reduced growth factor signaling both elevate resistance to oxidative stress, reduce macromolecular damage, and increase lifespan in model organisms. In rodents, both DR and decreased growth factor signaling reduce the incidence of tumors and slow down cognitive decline and aging. DR reduces cancer and cardiovascular disease and mortality in monkeys, and reduces metabolic traits associated with diabetes, cardiovascular disease and cancer in humans. Neoplasias and diabetes are also rare in humans with loss of function mutations in the growth hormone receptor. DR and reduced growth factor signaling may thus slow aging by similar, evolutionarily conserved, mechanisms. We review these conserved anti-aging pathways in model organisms, discuss their link to disease prevention in mammals, and consider the negative side effects that might hinder interventions intended to extend healthy lifespan in humans.",
"title": "Dietary Restriction, Growth Factors and Aging: from yeast to humans"
},
{
"docid": "MED-5239",
"text": "Epidemiological evidence points to increased dairy and meat consumption, staples of the Western diet, as major risk factors for the development of type 2 diabetes (T2D). This paper presents a new concept and comprehensive review of leucine-mediated cell signaling explaining the pathogenesis of T2D and obesity by leucine-induced over-stimulation of mammalian target of rapamycin complex 1 (mTORC1). mTORC1, a pivotal nutrient-sensitive kinase, promotes growth and cell proliferation in response to glucose, energy, growth factors and amino acids. Dairy proteins and meat stimulate insulin/insulin-like growth factor 1 signaling and provide high amounts of leucine, a primary and independent stimulator for mTORC1 activation. The downstream target of mTORC1, the kinase S6K1, induces insulin resistance by phosphorylation of insulin receptor substrate-1, thereby increasing the metabolic burden of β-cells. Moreover, leucine-mediated mTORC1-S6K1-signaling plays an important role in adipogenesis, thus increasing the risk of obesity-mediated insulin resistance. High consumption of leucine-rich proteins explains exaggerated mTORC1-dependent insulin secretion, increased β-cell growth and β-cell proliferation promoting an early onset of replicative β-cell senescence with subsequent β-cell apoptosis. Disturbances of β-cell mass regulation with increased β-cell proliferation and apoptosis as well as insulin resistance are hallmarks of T2D, which are all associated with hyperactivation of mTORC1. In contrast, the anti-diabetic drug metformin antagonizes leucine-mediated mTORC1 signaling. Plant-derived polyphenols and flavonoids are identified as natural inhibitors of mTORC1 and exert anti-diabetic and anti-obesity effects. Furthermore, bariatric surgery in obesity reduces increased plasma levels of leucine and other branched-chain amino acids. Attenuation of leucine-mediated mTORC1 signaling by defining appropriate upper limits of the daily intake of leucine-rich animal and dairy proteins may offer a great chance for the prevention of T2D and obesity, as well as other epidemic diseases of civilization with increased mTORC1 signaling, especially cancer and neurodegenerative diseases, which are frequently associated with T2D.",
"title": "Leucine signaling in the pathogenesis of type 2 diabetes and obesity"
},
{
"docid": "MED-3028",
"text": "OBJECTIVE The evidence on the association between fish consumption, dietary long-chain n-3 fatty acids, and risk of type 2 diabetes is inconsistent. We therefore performed a systematic review and meta-analysis of the available prospective evidence. RESEARCH DESIGN AND METHODS Studies were identified by searching the PubMed and EMBASE databases through 15 December 2011 and by reviewing the reference lists of retrieved articles. Prospective studies were included if they reported relative risk (RR) estimates with 95% CIs for the association between fish consumption and/or dietary long-chain n-3 fatty acids and incidence of type 2 diabetes. A dose-response random-effects model was used to combine study-specific RRs. Potential sources of heterogeneity were explored by prespecified stratifications. RESULTS Sixteen studies involving 527,441 participants and 24,082 diabetes cases were included. Considerable statistical heterogeneity in the overall summary estimates was partly explained by geographical differences. For each serving per week increment in fish consumption, the RRs (95% CIs) of type 2 diabetes were 1.05 (1.02–1.09), 1.03 (0.96–1.11), and 0.98 (0.97–1.00) combining U.S., European, and Asian/Australian studies, respectively. For each 0.30 g per day increment in long-chain n-3 fatty acids, the corresponding summary estimates were 1.17 (1.09–1.26), 0.98 (0.70–1.37), and 0.90 (0.82–0.98). CONCLUSIONS Results from this meta-analysis indicate differences between geographical regions in observed associations of fish consumption and dietary intake of long-chain n-3 fatty acids with risk of type 2 diabetes. In consideration of the heterogeneous results, the relationship warrants further investigation. Meanwhile, current public health recommendations on fish consumption should be upheld unchanged.",
"title": "Fish Consumption, Dietary Long-Chain n-3 Fatty Acids, and Risk of Type 2 Diabetes"
},
{
"docid": "MED-2129",
"text": "The act of increasing mass, either in non-dividing cells or in dividing cells seeking to provide new material for daughter cells, depends upon the continued presence of extracellular nutrients in order to conserve mass. For amino acid nutrients, it appears that their insufficiency for new protein synthesis is actively monitored by both prokaryotic and eukaryotic cells, eliciting appropriate cellular responses that may depend not only on bulk nutrient supply, but also on the abundance of specific amino acids. © 2012 The Author Journal compilation © 2012 FEBS.",
"title": "Amino acid sensing mechanisms: an Achilles heel in cancer?"
},
{
"docid": "MED-2397",
"text": "Background Studies have demonstrated ubiquitous human exposure to persistent organic pollutants (POPs) such as p,p′-diphenyldichloroethene (DDE) and polychlorinated biphenyls (PCBs). Although there is considerable evidence that POP exposures are associated with prevalent diabetes, these studies do not establish causality because the cross-sectional study design does not allow for assessment of temporality of the exposure–disease association. Prospective studies, however, have been lacking. Objectives This study was designed to determine whether POP body burdens are related to incidence of diabetes in a cohort of Great Lakes sport fish consumers. Methods The cohort was established in the early 1990s and followed through 2005. We tested serum for DDE and PCB congeners and assessed diabetes diagnosis, demographics, and fish consumption. Associations of diabetes with exposures were examined prospectively in participants without diabetes in 1994–1995, followed through 2005. Annual percent changes in DDE and PCB-132/153 from 1994 to 2005 were examined by diabetes status. Results DDE exposure was associated with incident diabetes. Incident diabetes was not associated with mono-ortho PCB-118, total PCBs, or years of sport fish consumption. Annual percent change in DDE and PCB-132/153 did not differ significantly by diabetes status. Conclusions This study demonstrates an association between DDE exposure and incident diabetes. The findings of an association of DDE with incident diabetes and the lack of effect of diabetes on annual percent change in POPs do not support the hypothesis that associations of POPs with diabetes are attributable to reverse causality. Additional studies should address the biological pathways by which DDE could affect glucose homeostasis.",
"title": "Organochlorine Exposure and Incidence of Diabetes in a Cohort of Great Lakes Sport Fish Consumers"
},
{
"docid": "MED-2502",
"text": "Dietary restriction (DR) without malnutrition is widely regarded to be a universal mechanism for prolonging lifespan. It is generally believed that the benefits of DR arise from eating fewer calories (termed caloric restriction, CR). Here we argue that, rather than calories, the key determinant of the relationship between diet and longevity is the balance of protein to non-protein energy ingested. This ratio affects not only lifespan, but also total energy intake, metabolism, immunity and the likelihood of developing obesity and associated metabolic disorders. Among various possible mechanisms linking macronutrient balance to lifespan, the nexus between the TOR and AMPK signaling pathways is emerging as a central coordinator.",
"title": "Macronutrient balance and lifespan"
},
{
"docid": "MED-5237",
"text": "Preface In all eukaryotes, the target of rapamycin (TOR) signaling pathway couples energy and nutrient abundance to the execution of cell growth and division, owing to the ability of TOR protein kinase to simultaneously sense energy, nutrients and stress, and, in metazoan, growth factors. Mammalian TOR complexes 1 and 2 (mTORC1 and mTORC2) exert their actions by regulating other important kinases, such as S6K and Akt. In the last few years, a significant advance in our understanding of the regulation and functions of mTOR has revealed its critical involvement in the onset and progression of diabetes, cancer and ageing.",
"title": "mTOR: from growth signal integration to cancer, diabetes and ageing"
},
{
"docid": "MED-2135",
"text": "Fisetin, a flavonol present in vegetables and fruits, possesses antioxidative and anti-inflammatory properties. In this study, we have demonstrated that fisetin prevents diet-induced obesity through regulation of the signaling of mammalian target of rapamycin complex 1 (mTORC1), a central mediator of cellular growth, cellular proliferation and lipid biosynthesis. To evaluate whether fisetin regulates mTORC1 signaling, we investigated the phosphorylation and kinase activity of the 70-kDa ribosomal protein S6 kinase 1 (S6K1) and mTORC1 in 3T3-L1 preadipocytes. Fisetin treatment of preadipocytes reduced the phosphorylation of S6K1 and mTORC1 in a time- and concentration-dependent manner. To further our understanding of how fisetin negatively regulates mTORC1 signaling, we analyzed the phosphorylation of S6K1, mTOR and Akt in fisetin-treated TSC2-knockdown cells. The results suggested that fisetin treatment inhibits mTORC1 activity in an Akt-dependent manner. Recent studies have shown that adipocyte differentiation is dependent on mTORC1 activity. Fisetin treatment inhibited adipocyte differentiation, consistent with the negative effect of fisetin on mTOR. The inhibitory effect of fisetin on adipogenesis is dependent of mTOR activity, suggesting that fisetin inhibits adipogenesis and the accumulation of intracellular triglycerides during adipocyte differentiation by targeting mTORC1 signaling. Fisetin supplementation in mice fed a high-fat diet (HFD) significantly attenuated HFD-induced increases in body weight and white adipose tissue. We also observed that fisetin efficiently suppressed the phosphorylation of Akt, S6K1 and mTORC1 in adipose tissue. Collectively, these results suggest that inhibition of mTORC1 signaling by fisetin prevents adipocyte differentiation of 3T3-L1 preadipocytes and obesity in HFD-fed mice. Therefore, fisetin may be a useful phytochemical agent for attenuating diet-induced obesity. Copyright © 2013 Elsevier Inc. All rights reserved.",
"title": "Fisetin regulates obesity by targeting mTORC1 signaling."
},
{
"docid": "MED-2506",
"text": "Long-term caloric restriction (CR) is a robust means of reducing age-related diseases and extending life span in multiple species, but the effects in humans are unknown. The low caloric intake, long life expectancy, and the high prevalence of centenarians in Okinawa have been used as an argument to support the CR hypothesis in humans. However, no long-term, epidemiologic analysis has been conducted on traditional dietary patterns, energy balance, and potential CR phenotypes for the specific cohort of Okinawans who are purported to have had a calorically restricted diet. Nor has this cohort's subsequent mortality experience been rigorously studied. Therefore, we investigated six decades of archived population data on the elderly cohort of Okinawans (aged 65-plus) for evidence of CR. Analyses included traditional diet composition, energy intake, energy expenditure, anthropometry, plasma DHEA, mortality from age-related diseases, and current survival patterns. Findings include low caloric intake and negative energy balance at younger ages, little weight gain with age, life-long low BMI, relatively high plasma DHEA levels at older ages, low risk for mortality from age-related diseases, and survival patterns consistent with extended mean and maximum life span. This study lends epidemiologic support for phenotypic benefits of CR in humans and is consistent with the well-known literature on animals with regard to CR phenotypes and healthy aging.",
"title": "Caloric restriction, the traditional Okinawan diet, and healthy aging: the diet of the world's longest-lived people and its potential impact on mor..."
},
{
"docid": "MED-2504",
"text": "It is well established that the target of rapamycin (TOR) protein kinase has pivotal roles in controlling cell functions (including protein synthesis, cell growth and cell proliferation) and is implicated in numerous human diseases. Mammalian TOR complex 1 (mTORC1) signalling is activated by hormones and growth factors, and is also stimulated by intracellular amino acids. Recent research has provided important new insight into the poorly understood mechanism by which amino acids activate mTORC1 signalling, showing that the protein kinase MAP4K3 and Rag GTPases have important roles in this. mTORC1 is known to control the G1/S transition of the cell cycle: new data show that (m)TORC1 also controls G2/M progression in yeast and mammals, albeit in contrasting ways.",
"title": "Nutrient control of TORC1, a cell-cycle regulator."
},
{
"docid": "MED-2391",
"text": "Objectives The objective of this article is to extend our previous studies of persistent organic pollutant (POP) contamination of U.S. food by measuring perfluorinated compounds (PFCs), organochlorine pesticides, and polychlorinated biphenyls (PCBs) in composite food samples. This study is part of a larger study reported in two articles, the other of which reports levels of polybrominated diphenyl ethers and hexabromocyclododecane brominated flame retardants in these composite foods [Schecter et al. 2010. Polybrominated diphenyl ethers (PBDEs) and hexabromocyclodecane (HBCD) in composite U.S. food samples, Environ Health Perspect 118:357–362]. Methods In this study we measured concentrations of 32 organochlorine pesticides, 7 PCBs, and 11 PFCs in composite samples of 31 different types of food (310 individual food samples) purchased from supermarkets in Dallas, Texas (USA), in 2009. Dietary intake of these chemicals was calculated for an average American. Results Contamination varied greatly among chemical and food types. The highest level of pesticide contamination was from the dichlorodiphenyltrichloroethane (DDT) metabolite p,p′- dichlorodiphenyldichloroethylene, which ranged from 0.028 ng/g wet weight (ww) in whole milk yogurt to 2.3 ng/g ww in catfish fillets. We found PCB congeners (28, 52, 101, 118, 138, 153, and 180) primarily in fish, with highest levels in salmon (PCB-153, 1.2 ng/g ww; PCB-138, 0.93 ng/g ww). For PFCs, we detected perfluorooctanoic acid (PFOA) in 17 of 31 samples, ranging from 0.07 ng/g in potatoes to 1.80 ng/g in olive oil. In terms of dietary intake, DDT and DDT metabolites, endosulfans, aldrin, PCBs, and PFOA were consumed at the highest levels. Conclusion Despite product bans, we found POPs in U.S. food, and mixtures of these chemicals are consumed by the American public at varying levels. This suggests the need to expand testing of food for chemical contaminants.",
"title": "Perfluorinated Compounds, Polychlorinated Biphenyls, and Organochlorine Pesticide Contamination in Composite Food Samples from Dallas, Texas, USA"
},
{
"docid": "MED-3307",
"text": "OBJECTIVE: workers in slaughterhouses and processing plants that handle pigs, and pork butchers/meatcutters have been little studied for health risks associated with employment, in spite of the fact that they are potentially exposed to oncogenic and non-oncogenic transmissible agents and chemical carcinogens at work. We report here on an update of mortality in 510 workers employed in abattoirs and processing plants that almost exclusively handled pigs and pork products. METHODS: standardized mortality ratios (SMRs) were estimated for the cohort as a whole, and in subgroups defined by race and sex, using the corresponding US general population mortality rates for comparison. Study subjects were followed up from January 1950 to December 2006, during which time 45% of them died. RESULTS: mortality was significantly increased overall in the cohort. A statistically significant excess of deaths was observed for colon and lung cancers in the entire cohort, SMR=2.7 (95% CI, 1.2-5.1), SMR=1.8 (95% CI, 1.1-2.7), respectively. Significant SMRs in the cohort as a whole were also observed for senile and pre-senile psychotic conditions (SMR=5.1, 95% CI, 1.4-13.1), and pneumonia (SMR=2.6, 95% CI, 1.3-4.8). An observed excess of subarachnoid hemorrhage was seen mainly in whites (SMR=10.1, 95% CI, 1.2-36.3). There was a suggestion of an excess of deaths from ischemic heart disease also, but the elevated SMR was confined to men and was not statistically significant. CONCLUSION: this study confirms the excess occurrence of lung and colon cancers, and stroke previously reported in this occupational group. New findings are the excess of risk for senile and pre-senile psychotic conditions and pneumonia, which together with the excess of colon cancer appear specific for pig/pork workers, as they were not evident in much larger studies of workers in abattoirs and processing plants handling cattle and sheep. However, caution should be exercised in interpreting these findings, since some of them could have occurred by chance, resulting from our examination of a large number of causes of death in multiple study subgroups. For the moment, the significance of these findings remains unknown until they are confirmed in larger studies of adequate statistical power. Studies that will take into account possible occupational and non-occupational confounding factors are needed. Copyright © 2011. Published by Elsevier Inc.",
"title": "Mortality in workers employed in pig abattoirs and processing plants."
},
{
"docid": "MED-1437",
"text": "Longevity, lifespan, cancer, cellular transformation, energy, calorie restriction, diabetes--what can tie together such a diversity of hot topics in biomedical research? Emerging findings suggest that the answer lies in understanding the functions of the recently discovered family of proteins known as Sirtuins. Barcelona hosted the first scientific meeting completely focused on these evolutionary conserved protein deacetylases, bringing together experts in the biochemistry to cellular biology, mice models, drug targeting and pathophysiology of these molecules. Their work, summarized here, establishes the Sirtuins as major players in cellular homeostasis and human diseases that act through a whole range of biochemical substrates and physiological processes. Undoubtedly, this is an increasingly expanding field that it is here to stay and growth.",
"title": "At the crossroad of lifespan, calorie restriction, chromatin and disease: meeting on sirtuins."
},
{
"docid": "MED-2395",
"text": "OBJECTIVE: Low-level exposure to some persistent organic pollutants (POPs) has recently become a focus because of their possible link with the risk of diabetes. RESEARCH DESIGN AND METHODS: Cross-sectional associations of the serum concentrations of POPs with diabetes prevalence were investigated in 2,016 adult participants in the National Health and Nutrition Examination Survey 1999-2002. Six POPs (2,2',4,4',5,5'-hexachlorobiphenyl, 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin, 1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin, oxychlordane, p,p'-dichlorodiphenyltrichloroethane, and trans-nonachlor) were selected, because they were detectable in >or=80% of participants. RESULTS: Compared with subjects with serum concentrations below the limit of detection, after adjustment for age, sex, race and ethnicity, poverty income ratio, BMI, and waist circumference, diabetes prevalence was strongly positively associated with lipid-adjusted serum concentrations of all six POPs. When the participants were classified according to the sum of category numbers of the six POPs, adjusted odds ratios were 1.0, 14.0, 14.7, 38.3, and 37.7 (P for trend < 0.001). The association was consistent in stratified analyses and stronger in younger participants, Mexican Americans, and obese individuals. CONCLUSIONS: There were striking dose-response relations between serum concentrations of six selected POPs and the prevalence of diabetes. The strong graded association could offer a compelling challenge to future epidemiologic and toxicological research.",
"title": "A strong dose-response relation between serum concentrations of persistent organic pollutants and diabetes: results from the National Health and Ex..."
},
{
"docid": "MED-4767",
"text": "We previously reported that chickens infected with the avian adenovirus SMAM-1 developed a unique syndrome characterized by excessive intra-abdominal fat deposition accompanied by paradoxically low serum cholesterol and triglyceride levels. There have been no previous reports of avian adenoviruses infecting humans. We screened the serum of 52 humans with obesity in Bombay, India, for antibodies against SMAM-1 virus using the agar gel precipitation test (AGPT) method. Bodyweights and serum cholesterol and triglyceride levels were compared in SMAM-1-positive (P-AGPT) and SMAM-1-negative (N-AGPT) groups. Ten subjects were positive for antibodies to SMAM-1, and 42 subjects did not have antibodies. The P-AGPT group had a significantly higher bodyweight (p < 0.02) and body mass index (p < 0.001) (95.1 +/- 2.1 kg and 35.3 +/- 1.5 kg/m2, respectively) compared with the N-AGPT group (80.1 +/- 0.6 kg and 30.7 +/- 0.6 kg/m2, respectively). Also, the P-AGPT group had significantly lower serum cholesterol (p < 0.02) and triglyceride (p < 0.001) values (4.65 mmol/L and 1.45 mmol/L, respectively) compared with the N-AGPT group (5.51 mmol/L and 2.44 mmol/L, respectively). Two subjects positive for SMAM-1 antibodies had antibodies against each others' serum, suggesting the presence of antigens in one or both. When these two serum samples were inoculated into chicken embryos, macroscopic lesions compatible with SMAM-1 infection developed. The inoculation of serum from N-AGPT subjects did not produce such lesions. The presence of increased obesity, antibodies to SMAM-1, reduced levels of blood lipids, and viremia that produces a typical infection in chicken embryos suggests that SMAM-1, or a serologically similar human virus, may be involved in the cause of obesity in some humans.",
"title": "Association of adenovirus infection with human obesity."
},
{
"docid": "MED-3319",
"text": "Background In October 2007, a cluster of patients experiencing a novel polyradiculoneuropathy was identified at a pork abattoir (Plant A). Patients worked in the primary carcass processing area (warm room); the majority processed severed heads (head-table). An investigation was initiated to determine risk factors for illness. Methods and Results Symptoms of the reported patients were unlike previously described occupational associated illnesses. A case-control study was conducted at Plant A. A case was defined as evidence of symptoms of peripheral neuropathy and compatible electrodiagnostic testing in a pork abattoir worker. Two control groups were used - randomly selected non-ill warm-room workers (n = 49), and all non-ill head-table workers (n = 56). Consenting cases and controls were interviewed and blood and throat swabs were collected. The 26 largest U.S. pork abattoirs were surveyed to identify additional cases. Fifteen cases were identified at Plant A; illness onsets occurred during May 2004–November 2007. Median age was 32 years (range, 21–55 years). Cases were more likely than warm-room controls to have ever worked at the head-table (adjusted odds ratio [AOR], 6.6; 95% confidence interval [CI], 1.6–26.7), removed brains or removed muscle from the backs of heads (AOR, 10.3; 95% CI, 1.5–68.5), and worked within 0–10 feet of the brain removal operation (AOR, 9.9; 95% CI, 1.2–80.0). Associations remained when comparing head-table cases and head-table controls. Workers removed brains by using compressed air that liquefied brain and generated aerosolized droplets, exposing themselves and nearby workers. Eight additional cases were identified in the only two other abattoirs using this technique. The three abattoirs that used this technique have stopped brain removal, and no new cases have been reported after 24 months of follow up. Cases compared to controls had higher median interferon-gamma (IFNγ) levels (21.7 pg/ml; vs 14.8 pg/ml, P<0.001). Discussion This novel polyradiculoneuropathy was associated with removing porcine brains with compressed air. An autoimmune mechanism is supported by higher levels of IFNγ in cases than in controls consistent with other immune mediated illnesses occurring in association with neural tissue exposure. Abattoirs should not use compressed air to remove brains and should avoid procedures that aerosolize CNS tissue. This outbreak highlights the potential for respiratory or mucosal exposure to cause an immune-mediated illness in an occupational setting.",
"title": "Epidemiologic Investigation of Immune-Mediated Polyradiculoneuropathy among Abattoir Workers Exposed to Porcine Brain"
},
{
"docid": "MED-2511",
"text": "Residents of Okinawa, the southernmost prefecture of Japan, are known for their long average life expectancy, high numbers of centenarians, and accompanying low risk of age-associated diseases. Much of the longevity advantage in Okinawa is thought to be related to a healthy lifestyle, particularly the traditional diet, which is low in calories yet nutritionally dense, especially with regard to phytonutrients in the form of antioxidants and flavonoids. Research suggests that diets associated with a reduced risk of chronic diseases are similar to the traditional Okinawan diet, that is, vegetable and fruit heavy (therefore phytonutrient and antioxidant rich) but reduced in meat, refined grains, saturated fat, sugar, salt, and full-fat dairy products. Many of the characteristics of the diet in Okinawa are shared with other healthy dietary patterns, such as the traditional Mediterranean diet or the modern DASH (Dietary Approaches to Stop Hypertension) diet. Features such as the low levels of saturated fat, high antioxidant intake, and low glycemic load in these diets are likely contributing to a decreased risk for cardiovascular disease, some cancers, and other chronic diseases through multiple mechanisms, including reduced oxidative stress. A comparison of the nutrient profiles of the three dietary patterns shows that the traditional Okinawan diet is the lowest in fat intake, particularly in terms of saturated fat, and highest in carbohydrate intake, in keeping with the very high intake of antioxidant-rich yet calorie-poor orange-yellow root vegetables, such as sweet potatoes, and green leafy vegetables. Deeper analyses of the individual components of the Okinawan diet reveal that many of the traditional foods, herbs, or spices consumed on a regular basis could be labeled \"functional foods\" and, indeed, are currently being explored for their potential health-enhancing properties.",
"title": "The Okinawan diet: health implications of a low-calorie, nutrient-dense, antioxidant-rich dietary pattern low in glycemic load."
},
{
"docid": "MED-2388",
"text": "Insulin resistance and the defective function of pancreatic β-cells can occur several years before the development of type 2 diabetes. It is necessary to investigate and clarify the integrated effects of moderate-to-high exposure to dioxins and mercury on the pancreatic endocrine function. This cross-sectional study investigated 1449 non-diabetic residents near a deserted pentachlorophenol and chloralkali factory. Metabolic syndrome related factors were measured to examine associations with serum dioxin and blood mercury. We also investigated associations between insulin resistance (HOMA-IR > 75th percentile), defective pancreatic β-cells function (HOMA β-cell > 75th percentile), serum dioxins and blood mercury. After adjusting for confounding factors, we found that insulin resistance increased with serum dioxins (b = 0.13, P < 0.001) and blood mercury (b = 0.01, P < 0.001). Moreover, participants with higher serum dioxins or blood mercury were at a significantly increasing risk for insulin resistance (P(trend) < 0.001). The joint highest tertile of serum dioxins and blood mercury was associated with elevated HOMA-IR at 11 times the odds of the joint lowest tertile (AOR 11.00, 95% CI: 4.87, 26.63). We hypothesize that simultaneous exposure to dioxins and mercury heightens the risk of insulin resistance more than does individual exposure. Copyright © 2010 Elsevier B.V. All rights reserved.",
"title": "Simultaneous exposure of non-diabetics to high levels of dioxins and mercury increases their risk of insulin resistance."
},
{
"docid": "MED-2398",
"text": "The worldwide increasing prevalence of type 2 diabetes mellitus (T2DM) poses an immense public health hazard leading to a variety of complications such as cardiovascular diseases, nephropathy and neuropathy. Diet, as a key component of a healthy human lifestyle, plays an important role in the prevention and management of T2DM and its complications. The dietary n-3 polyunsaturated fatty acids (PUFAs) have been associated with various favourable functions such as anti-inflammatory effects, improving endothelial function, controlling the blood pressure, and reducing hypertriglyceridemia and insulin insensitivity. According to some epidemiological studies, a lower prevalence of T2DM was found in populations consuming large amounts of seafood products, which are rich in n-3 PUFAs. However, the evidence on the relation between fish intake, dietary n-3 PUFAs, and risk of T2DM is controversial. Therefore, this paper aimed to review the epidemiological and clinical studies on the role of dietary n-3 PUFAs in T2DM. Also, the limitations of these studies and the need for potential further research on the subject are discussed. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.",
"title": "Role of dietary n-3 polyunsaturated fatty acids in type 2 diabetes: a review of epidemiological and clinical studies."
},
{
"docid": "MED-2405",
"text": "The contribution of exposure to persistent organic pollutants (POPs) to the incidence of diabetes has received little attention until recently. A number of reports have emerged, however, concerning elevated diabetes in persons occupationally exposed to dioxin. United States (US) Air Force personnel in Vietnam who sprayed Agent Orange containing dioxin as a contaminant had elevated rates of diabetes, leading to US government compensation for diabetes in these veterans. Recent studies in populations exposed to polychlorinated biphenyls (PCBs) and chlorinated pesticides found a dose-dependent elevated risk of diabetes. An elevation in risk of diabetes in relation to levels of several POPs has been demonstrated by two different groups using the National Health and Nutrition Examination Survey (NHANES), a random sampling of US citizens. The strong associations seen in quite different studies suggest the possibility that exposure to POPs could cause diabetes. One striking observation is that obese persons that do not have elevated POPs are not at elevated risk of diabetes, suggesting that the POPs rather than the obesity per se is responsible for the association. Although a specific mechanism is not known, most POPs induce a great number and variety of genes, including several that alter insulin action. Because diabetes is a dangerous disease that is increasing in frequency throughout the world, further study of the possibility that exposure to POPs contributes to the etiology of diabetes is critical.",
"title": "Environmental contaminants as risk factors for developing diabetes."
},
{
"docid": "MED-2514",
"text": "Healthy life span is rapidly increasing and human aging seems to be postponed. As recently exclaimed in Nature, these findings are so perplexing that they can be dubbed the 'longevity riddle'. To explain current increase in longevity, I discuss that certain genetic variants such as hyper-active mTOR (mTarget of Rapamycin) may increase survival early in life at the expense of accelerated aging. In other words, robustness and fast aging may be associated and slow-aging individuals died prematurely in the past. Therefore, until recently, mostly fast-aging individuals managed to survive into old age. The progress of civilization (especially 60 years ago) allowed slow-aging individuals to survive until old age, emerging as healthy centenarians now. I discuss why slow aging is manifested as postponed (healthy) aging, why the rate of deterioration is independent from aging and also entertain hypothetical use of rapamycin in different eras as well as the future of human longevity.",
"title": "Why human lifespan is rapidly increasing: solving \"longevity riddle\" with \"revealed-slow-aging\" hypothesis"
},
{
"docid": "MED-2139",
"text": "The mammalian target of rapamycin (mTOR) plays a key role in the regulation of cellular metabolism, growth and proliferation. It forms two multi-protein complexes known as complex 1 (mTORC1) and 2 (mTORC2). Raptor and Rictor are the core proteins for mTORC1 and mTORC2, respectively. This study examines the relationship between mTORC1, Rictor and Raptor mRNA expression and human breast cancer. Furthermore, the correlation between mTORC1 and hTERT was investigated. Breast cancer tissues (n=150) and normal tissues (n=31) were analysed using reverse transcription and quantitative PCR. Transcript levels were correlated with clinicopathological data. Higher mTOR expression was noted in breast cancer tissue (P=0.0018), higher grade tumours (grade 2 vs. 3, P=0.047), in ductal tumours (P=0.0014), and was associated with worse overall survival (P=0.01). Rictor expression was significantly higher in background breast tissues compared with tumours and was inversely related to the Nottingham Prognostic Index (NPI1 vs. 2, P=0.03) and tumour grade (grade 1 vs. 3, P=0.01) and was associated with better overall (P=0.037) and disease-free survival (P=0.048). The mRNA expression of Raptor was higher in tumours compared with normal tissues. Furthermore, the expression of Raptor was associated with a higher tumour grade (grade 1 vs. 3, P=0.027). A highly significant positive correlation between mTOR and hTERT (P<0.00001) was observed. These observations are consistent with the role of mTORC1 in the anti-apoptosis pathway and suggest that selective inhibitors of mTORC1 may be more efficacious in human breast cancer. Our findings support the hypothesis that mTORC1 is an important upregulator of telomerase in breast cancer.",
"title": "Prognostic and therapeutic implications of mTORC1 and Rictor expression in human breast cancer."
},
{
"docid": "MED-2520",
"text": "This article discusses that the traditional analogy of an aging organism with a rusting (albeit self-repairing) car is misleading. The true analogy is a speeding car that enters a low-speed zone and damages itself because it does not and cannot slow down. For such a car without brakes (and actually without a driver), aging from rusting never occurs. Using simple analogies (although turning gerontology upside down), this article discusses the origin of aging, how overactivation of the mTOR (Target of Rapamycin) pathway causes aging, why aging causes damage (organ damage) not damage causes aging, the link between aging and age-related diseases, slow aging versus aging tolerance and suppression of aging with rapamycin.",
"title": "TOR-driven aging: speeding car without brakes."
},
{
"docid": "MED-1798",
"text": "The most important factors leading to fat accumulation in children are genetic inheritance, endocrine alterations, and behavioural/environmental causes. In addition, experimental animal studies have shown that infections due to various pathogens can lead to overweight and obesity conditions, and studies of humans have found that the incidence of seroconversion against some of these may be significantly more frequent in obese adults and children than in normal subjects. However, the results of these studies are not conclusive and, in some cases, have raised more questions than answers. We reviewed the literature concerning the role of adenovirus 36 (AD-36), the most widely studied infectious agent in animals and humans, because of its potential association with childhood obesity. The available evidence suggests that more studies are needed to evaluate whether or not the association between the presence of AD-36 antibodies and obesity is simply unrelated, and to verify whether there are subjects that have greater tendency to become obese because more easily susceptible to AD-36 infection or with a predisposition to suffer from persistent viral infection more easily leading to the development of obesity. If it is demonstrated that AD-36 does play a role in obesity, it will be important to investigate possible vaccines against the infection itself or antiviral drugs capable of inhibiting disease progression. Copyright © 2012 Elsevier B.V. All rights reserved.",
"title": "Adenovirus 36 infection and obesity."
},
{
"docid": "MED-3314",
"text": "OBJECTIVES: Evidence suggests that certain occupations and related exposures may increase the risk of malignant lymphoma. Farming, printing and paper industry, wood processing, meat handling and processing, welding, shoe and leather manufacturing and teaching profession are among the categories that have been implicated in previous studies. The relationship between occupation and malignant lymphoma has been investigated in a large European prospective study. METHODS: We investigated occupational risks for lymphomas in the European Prospective Investigation into Cancer and Nutrition (EPIC). The mean follow-up time for 348,555 subjects was 9 years (SD: 2 years). The analysis was based on 866 and 48 newly diagnosed cases of non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL). These were identified in the EPIC subcohorts with occupational data. Data on 52 occupations were collected through standardised questionnaires. Cox proportional hazard models were used to explore the association between occupation and risk of malignant lymphoma. RESULTS: The following occupations were positively associated with malignant NHL after adjustment for study centre, age, sex, socioeconomic status (SES), smoking and alcohol: butchers (HR=1.53, 95% CI 1.05 to 2.48, including multiple myeloma/plasmacytoma; HR=1.30, 95% CI 1.00 to 2.66, excluding multiple myeloma/plasmacytoma) and car repair workers (HR=1.50, 95% CI 1.01 to 2.00, including multiple myeloma/plasmacytoma; HR=1.51, 95% CI 1.01 to 2.31, excluding multiple myeloma/plasmacytoma). HL was associated with gasoline station occupation (HR=4.59, 95% CI 1.08 to 19.6). CONCLUSION: The findings in this current study of a higher risk of NHL among car repair workers and butchers and a higher risk of HL among gasoline station workers suggest a possible role from occupationally related exposures, such as solvents and zoonotic viruses, as risk factors for malignant lymphoma.",
"title": "Occupation and risk of lymphoma: a multicentre prospective cohort study (EPIC)."
},
{
"docid": "MED-3313",
"text": "INTRODUCTION: Asbestos is banned in most Western countries but related malignancies are still of clinical concern because of their long latencies. This review identifies and addresses some controversial occupational and clinical aspects of asbestos-related malignancies. METHODS: Papers published in English from 1980 to 2009 were retrieved from PubMed. A total of 307 original articles were identified and 159 were included. ASSESSMENT OF EXPOSURE: The retrospective assessment of exposure is usually performed by using questionnaires and job exposure matrices and by careful collection of medical history. In this way crucial information about manufacturing processes and specific jobs can be obtained. In addition, fibers and asbestos bodies are counted in lung tissue, broncho-alveolar lavage, and sputum, but different techniques and interlaboratory variability hamper the interpretation of reported measurements. SCREENING FOR MALIGNANCIES: The effectiveness of low-dose chest CT screening in exposed workers is debatable. Several biomarkers have also been considered to screen individuals at risk for lung cancer and mesothelioma but reliable signatures are still missing. ATTRIBUTION OF LUNG CANCER: Exposures correlating with lung cancer are high and in the same range where asbestosis occurs. However, the unresolved question is whether the presence of fibrosis is a requirement for the attribution of lung cancer to asbestos. The etiology of lung cancer is difficult to define in cases of low-level asbestos exposure and concurrent smoking habits. MESOTHELIOMA: The diagnosis of malignant mesothelioma may also be difficult, because of procedures in sampling, fixation, and processing, and uses of immunohistochemical probes. CONCLUSIONS: Assessment of exposure is crucial and requires accurate medical and occupational histories. Quantitative analysis of asbestos body burden is better performed in digested lung tissues by counting asbestos bodies by light microscopy and/or uncoated fibers by transmission electron microscopy. The benefits of screenings for asbestos-related malignancies are equivocal. The attribution of lung cancer to asbestos exposure is difficult in a clinical setting because of the need to assess asbestos body burden and the fact that virtually all these patients are also tobacco smokers or former smokers. Given the premise that asbestosis is necessary to causally link lung cancer to asbestos, it follows that the assessment of both lung fibrosis and asbestos body burden is necessary.",
"title": "Occupational toxicology of asbestos-related malignancies."
},
{
"docid": "MED-4727",
"text": "The objective of this study was to estimate the intake of organic tin compounds from foodstuffs in a Finnish market basket. The study was conducted by collecting 13 market baskets from supermarkets and market places in the city of Kuopio, eastern Finland. Altogether 115 different food items were bought. In each basket, foodstuffs were mixed in proportion to their consumption and analysed by GC/MS for seven organic tin compounds (mono-, di-, and tributyltin, mono-, di-, and triphenyltin, and dioctyltin). Organotin compounds were detected in only four baskets, with the fish basket containing the largest number of different organotins. The European Food Safety Authority has established a tolerable daily intake of 250 ng kg(-1) body weight for the sum of dibutyltin, tributyltin, triphenyltin and dioctyltin. According to this study, the daily intake of these compounds was 2.47 ng kg(-1) body weight, of which 81% originated from the fish basket. This exposure is only 1% of the tolerable daily intake and poses negligible risk to the average consumer. However, for consumers eating large quantities of fish from contaminated areas, the intake may be much higher.",
"title": "Dietary intake of organotin compounds in Finland: a market-basket study."
},
{
"docid": "MED-2127",
"text": "The mammalian target of rapamycin (mTOR) is a conserved protein kinase involved in a multitude of cellular processes including cell growth. Increased mTOR activation is observed in multiple human cancers and inhibition of mTOR has proven efficacious in numerous clinical trials. mTOR comprises two complexes, termed mTORC1 and mTORC2. Both complexes respond to growth factors, whereas only mTORC1 is controlled by nutrients, such as glucose and amino acids. Since the discovery of mTOR, extensive studies have intricately detailed the molecular mechanisms by which mTORC1 is regulated. Somewhat paradoxically, amino acid induced mTORC1 activation—arguably the most essential stimulus leading to mTORC1 activation—is the least understood. Here we review the current knowledge of nutrient dependent regulation of mTORC1.",
"title": "Nutrient Signaling to mTOR and Cell Growth"
},
{
"docid": "MED-3292",
"text": "The human APOBEC3G protein is an innate anti-viral factor that can dominantly inhibit the replication of some endogenous and exogenous retroviruses. The prospects of purposefully harnessing such an anti-viral defense are under investigation. Here, long-term co-culture experiments were used to show that porcine endogenous retrovirus (PERV) transmission from pig to human cells is reduced to nearly undetectable levels by expressing human APOBEC3G in virus-producing pig kidney cells. Inhibition occurred by a deamination-independent mechanism, likely after particle production but before the virus could immortalize by integration into human genomic DNA. PERV inhibition did not require the DNA cytosine deaminase activity of APOBEC3G and, correspondingly, APOBEC3G-attributable hypermutations were not detected. In contrast, over-expression of the sole endogenous APOBEC3 protein of pigs failed to interfere significantly with PERV transmission. Together, these data constitute the first proof-of-principle demonstration that APOBEC3 proteins can be used to fortify the innate anti-viral defenses of cells to prevent the zoonotic transmission of an endogenous retrovirus. These studies suggest that human APOBEC3G-transgenic pigs will provide safer, PERV-less xenotransplantation resources and that analogous cross-species APOBEC3-dependent restriction strategies may be useful for thwarting other endogenous as well as exogenous retrovirus infections.",
"title": "The Restriction of Zoonotic PERV Transmission by Human APOBEC3G"
},
{
"docid": "MED-1810",
"text": "BACKGROUND: We previously reported that human adenovirus Ad-36 induces adiposity and paradoxically lower levels of serum cholesterol (CHOL) and triglycerides (TG) in animals. OBJECTIVE: To evaluate the transmissibility of Ad-36 and Ad-36 induced adiposity using a chicken model. DESIGN: Experiment 1--four chickens were housed (two per cage) and one from each cage was inoculated with Ad-36. Duration of presence of Ad-36 DNA in the blood of all chickens was monitored. Experiment 2--two groups of chickens were intranasally inoculated with Ad-36 (infected donors, I-D) or media (control donors, C-D). Blood drawn 36 h later from I-D and C-D groups was inoculated into wing veins of recipient chickens (infected receivers, I-R, and control receivers, C-R, respectively). On sacrifice, 5 weeks post-inoculation, blood was drawn, body weight noted and visceral fat was separated and weighed. RESULTS: Experiment 1--Ad-36 DNA appeared in the blood of the inoculated chickens and that of uninoculated chickens (cage mates) within 12 h of inoculation and the viral DNA persisted up to 25 days in the blood. Experiment 2--compared with C-D, visceral and total body fat were significantly greater and CHOL significantly lower for the I-D and I-R. TG were significantly lower for the I-D. Ad-36 was isolated from 12 out of 16 blood samples of the I-D that were used for inoculating I-R chickens. Ad-36 DNA was present in the blood and the adipose tissue of the I-D and I-R but not in the skeletal muscles of animals selected randomly for testing. CONCLUSION: As seen in experiment 1, Ad-36 infection can be transmitted horizontally from an infected chicken to another chicken sharing the cage. Additionally, experiment 2 demonstrated blood-borne transmission of Ad-36-induced adiposity in chickens. Transmissibility of Ad-36-induced adiposity in chicken model raises serious concerns about such a possibility in humans that needs further investigation.",
"title": "Transmissibility of adenovirus-induced adiposity in a chicken model."
},
{
"docid": "MED-2138",
"text": "CONTEXT: Restricting caloric intake is one of the most effective ways to extend lifespan and to reduce spontaneous tumor occurrence in experimental animals, but whether similar associations hold in humans has not been appropriately studied. OBJECTIVE: To determine whether caloric restriction in early life reduces the risk of invasive breast cancer. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study using data from the Swedish Inpatient Registry, the Swedish Cancer Registry, the Swedish Death Registry, and the Swedish Fertility Registry. Participants were 7303 Swedish women hospitalized for anorexia nervosa prior to age 40 years between 1965 and 1998. Women were excluded (n = 31) if they were diagnosed with cancer prior to their first discharge from hospitalization for anorexia nervosa. MAIN OUTCOME MEASURE: Incidence of invasive breast cancer. RESULTS: Compared with the Swedish general population, women hospitalized for anorexia nervosa prior to age 40 years had a 53% (95% confidence interval [CI], 3%-81%) lower incidence of breast cancer; nulliparous women with anorexia nervosa had a 23% (95% CI, 79% higher to 75% lower) lower incidence, and parous women with anorexia nervosa had a 76% (95% CI, 13%-97%) lower incidence. CONCLUSIONS: Severe caloric restriction in humans may confer protection from invasive breast cancer. Low caloric intake prior to first birth followed by a subsequent pregnancy appears to be associated with an even more pronounced reduction in risk.",
"title": "Caloric restriction and incidence of breast cancer."
},
{
"docid": "MED-3310",
"text": "We observed five consecutive cases of Hypersensitivity Pneumonitis in subjects working in a salami factory. The workers had to clean the white mould growing on salami surface using a manual wire brush. The five patients (four female) had a mean age of 39 +/- 15 years; two were smokers. Three patients had an acute clinical presentation with fever, dyspnoea, dry cough, oxygen desaturation, and presented at the emergency department with suspected diagnosis of community acquired pneumonia. The mean latency for developing respiratory symptoms was 11.6 days. Pulmonary function test demonstrated a reduction in diffusing capacity (DLCO) in all 5 patients (60 +/- 15% of predicted value). Skin prick test was positive for Penicillium spp in 3 cases and for Cladosporium and Aspergillus spp in 2 others. Specific IgG antibodies against Penicillium spp were positive in 3 subjects; 2 were positive for Aspergillus Fumigatus. The prevailing radiological pattern was a ground glass appearance in the three patients with acute clinical onset and a centrilobular one in patients with subacute onset. All patients were advised to avoid exposure to the antigens. Follow-up visits including pulmonary function testing, and DLCO measurement were conducted at one, three and six months. HRCT was performed at six month. Four subjects had a complete radiological and clinical resolution after changing work. Only one patient was treated with oral steroids for severe dyspnoea and progressive reduction of DLCO, gaining a complete radiological and clinical stability at six months.",
"title": "A new type of Hypersensitivity Pneumonitis: salami brusher's disease."
},
{
"docid": "MED-2407",
"text": "Background Persistent organic pollutants (POPs) are hazardous chemicals omnipresent in our food chain, which have been internationally regulated to ensure public health. Initially described for their potency to affect reproduction and promote cancer, recent studies have highlighted an unexpected implication of POPs in the development of metabolic diseases like type 2 diabetes and obesity. Based on this novel knowledge, this article aims at stimulating discussion and evaluating the effectiveness of current POP legislation to protect humans against the risk of metabolic diseases. Furthermore, the regulation of POPs in animal food products in the European Union (EU) is addressed, with a special focus on marine food since it may represent a major source of POP exposure to humans. Discussion There is mounting scientific evidence showing that current POP risk assessment and regulation cannot effectively protect humans against metabolic disorders. Better regulatory control of POPs in dietary products should be of high public health priority. Summary The general population is exposed to sufficient POPs, both in term of concentration and diversity, to induce metabolic disorders. This situation should attract the greatest attention from the public health and governmental authorities.",
"title": "Public health concern behind the exposure to persistent organic pollutants and the risk of metabolic diseases"
},
{
"docid": "MED-2411",
"text": "The relationship between omega-3 polyunsaturated fatty acids (n-3 PUFA) from seafood (eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA) or plant (alpha-linolenic acid, ALA) sources and risk of type 2 diabetes mellitus (DM) remains unclear. We systematically searched multiple literature databases through June 2011 to identify prospective studies examining relations of dietary n-3 PUFA, dietary fish and/or seafood, and circulating n-3 PUFA biomarkers with incidence of DM. Data were independently extracted in duplicate by 2 investigators, including multivariate-adjusted relative risk (RR) estimates and corresponding 95% CIs. Generalized least-squares trend estimation was used to assess dose-response relationships, with pooled summary estimates calculated by both fixed-effect and random-effect models. From 288 identified abstracts, 16 studies met inclusion criteria, including 18 separate cohorts comprising 540,184 individuals and 25,670 cases of incident DM. Consumption of fish and/or seafood was not significantly associated with DM (n=13 studies; RR per 100g/d=1.12, 95% CI=0.94, 1.34); nor were consumption of EPA+DHA (n=16 cohorts; RR per 250mg/d=1.04, 95% CI=0.97, 1.10) or circulating levels of EPA+DHA biomarkers (n=5 cohorts; RR per 3% of total fatty acids=0.94, 95% CI=0.75, 1.17). Both dietary ALA (n=7 studies; RR per 0.5g/d=0.93, 95% CI=0.83, 1.04) and circulating ALA biomarker levels (n=6 studies; RR per 0.1% of total fatty acid=0.90, 95% CI=0.80, 1.00, P=0.06) were associated with non-significant trend towards lower risk of DM. Substantial heterogeneity (I2~80%) was observed among studies of fish/seafood or EPA+DHA and DM; moderate heterogeneity (<55%) was seen for dietary and biomarker ALA and DM. In unadjusted meta-regressions, study location (Asia vs. North America/Europe), mean BMI, and duration of follow-up each modified the association between fish/seafood and EPA+DHA consumption and DM risk (P-Interaction ≤ 0.02 each). We had limited statistical power to determine the independent effect of these sources of heterogeneity due to their high collinearity. The overall pooled findings do not support either major harms or benefits of fish/seafood or EPA+DHA on development of DM, and suggest that ALA may be associated with modestly lower risk. Reasons for potential heterogeneity of effects, which could include true biologic heterogeneity, publication bias, or chance, deserve further investigation.",
"title": "Omega-3 Fatty Acids and incident Type 2 Diabetes: A Systematic Review and Meta-Analysis"
},
{
"docid": "MED-2943",
"text": "BACKGROUND: Western diets, which typically contain large amounts of energy-dense processed foods, together with a sedentary lifestyle are associated with increased cardiometabolic risk. We evaluated the long-term effects of consuming a low-calorie low-protein vegan diet or performing regular endurance exercise on cardiometabolic risk factors. METHODS: In this cross-sectional study, cardiometabolic risk factors were evaluated in 21 sedentary subjects, who had been on a low-calorie low-protein raw vegan diet for 4.4 +/- 2.8 years, (mean age, 53.1 +/- 11 yrs), 21 body mass index (BMI)-matched endurance runners consuming Western diets, and 21 age- and gender-matched sedentary subjects, consuming Western diets. RESULTS: BMI was lower in the low-calorie low-protein vegan diet (21.3 +/- 3.1 kg/m(2)) and endurance runner (21.1 +/- 1.6 kg/m(2)) groups than in the sedentary Western diet group (26.5 +/- 2.7 kg/m(2)) (p < 0.005). Plasma concentrations of lipids, lipoproteins, glucose, insulin, C-reactive protein, blood pressure (BP), and carotid artery intima-media thickness were lower in the low-calorie low-protein vegan diet and runner groups than in the Western diet group (all p < 0.05). Both systolic and diastolic BP were lower in the low-calorie low-protein vegan diet group (104 +/- 15 and 62 +/- 11 mm Hg) than in BMI-matched endurance runners (122 +/- 13 and 72 +/- 9 mmHg) and Western diet group (132 +/- 14 and 79 +/- 8 mm Hg) (p < 0.001); BP values were directly associated with sodium intake and inversely associated with potassium and fiber intake. CONCLUSIONS: Long-term consumption of a low-calorie low-protein vegan diet or regular endurance exercise training is associated with low cardiometabolic risk. Moreover, our data suggest that specific components of a low-calorie low-protein vegan diet provide additional beneficial effects on blood pressure.",
"title": "Long-term low-calorie low-protein vegan diet and endurance exercise are associated with low cardiometabolic risk."
},
{
"docid": "MED-1806",
"text": "OBJECTIVE Ad36, a human adenovirus, increases adiposity but improves glycemic control in animal models. Similarly, natural Ad36 infection is cross-sectionally associated with greater adiposity and better glycemic control in humans. This study compared longitudinal observations in indices of adiposity (BMI and body fat percentage) and glycemic control (fasting glucose and insulin) in Ad36-infected versus uninfected adults. RESEARCH DESIGN AND METHODS Baseline sera from Hispanic men and women (n = 1,400) were screened post hoc for the presence of Ad36-specific antibodies. Indices of adiposity and glycemic control at baseline and at ∼10 years past the baseline were compared between seropositive and seronegative subjects, with adjustment for age and sex. In addition to age and sex, indices of glycemic control were adjusted for baseline BMI and were analyzed only for nondiabetic subjects. RESULTS Seropositive subjects (14.5%) had greater adiposity at baseline, compared with seronegative subjects. Longitudinally, seropositive subjects showed greater adiposity indices but lower fasting insulin levels. Subgroup analyses revealed that Ad36-seropositivity was associated with better baseline glycemic control and lower fasting insulin levels over time in the normal-weight group (BMI ≤25 kg/m2) and longitudinally, with greater adiposity in the overweight (BMI 25–30 kg/m2) and obese (BMI >30 kg/m2) men. Statistically, the differences between seropositive and seronegative individuals were modest in light of the multiple tests performed. CONCLUSIONS This study strengthens the plausibility that in humans, Ad36 increases adiposity and attenuates deterioration of glycemic control. Panoptically, the study raises the possibility that certain infections may modulate obesity or diabetes risk. A comprehensive understanding of these under-recognized factors is needed to effectively combat such metabolic disorders.",
"title": "Long-Term Changes in Adiposity and Glycemic Control Are Associated With Past Adenovirus Infection"
},
{
"docid": "MED-2517",
"text": "Many experts in the biology of ageing believe that pharmacological interventions to slow ageing are a matter of ‘when’ rather than ‘if’. A leading target for such interventions is the nutrient response pathway defined by the mechanistic target of rapamycin (mTOR). Inhibition of this pathway extends lifespan in model organisms and confers protection against a growing list of age-related pathologies. Characterized inhibitors of this pathway are already clinically approved, and others are under development. Although adverse side effects currently preclude use in otherwise healthy individuals, drugs that target the mTOR pathway could one day become widely used to slow ageing and reduce age-related pathologies in humans.",
"title": "mTOR is a key modulator of ageing and age-related disease"
},
{
"docid": "MED-5235",
"text": "Several prospective studies have reported that risk of type 2 diabetes (T2DM) is elevated in meat consumers, especially when processed meats are consumed. Elevated risks of coronary heart disease (CHD) and stroke in meat consumers have also been reported. In this overview, the evidence regarding meat consumption and the risk of diabetes, both type 1 diabetes (T1DM) and T2DM and their macro- and microvascular complications, is reviewed. For T2DM, we performed a new meta-analysis including publications up to October 2012. For T1DM, only a few studies have reported increased risks for meat consumers or for high intake of saturated fatty acids and nitrates and nitrites. For T2DM, CHD, and stroke, the evidence is strongest. Per 100 g of total meat, the pooled relative risk (RR) for T2DM is 1.15 (95 % CI 1.07-1.24), for (unprocessed) red meat 1.13 (95 % CI 1.03-1.23), and for poultry 1.04 (95 % CI 0.99-1.33); per 50 g of processed meat, the pooled RR is 1.32 (95 % CI 1.19-1.48). Hence, the strongest association regarding T2DM is observed for processed (red) meat. A similar observation has been made for CHD. For stroke, however, a recent meta-analysis shows moderately elevated risks for meat consumers, for processed as well as for fresh meats. For the microvascular complications of diabetes, few prospective data were available, but suggestions for elevated risks can be derived from findings on hyperglycemia and hypertension. The results are discussed in the light of the typical nutrients and other compounds present in meat--that is, saturated and trans fatty acids, dietary cholesterol, protein and amino acids, heme-iron, sodium, nitrites and nitrosamines, and advanced glycation end products. In light of these findings, a diet moderate to low in red meat, unprocessed and lean, and prepared at moderate temperatures is probably the best choice from the public health point of view.",
"title": "Meat consumption, diabetes, and its complications."
},
{
"docid": "MED-1431",
"text": "Objective: Several studies report that diabetes increases risk of cognitive impairment; some have hypothesized that advanced glycation end products (AGEs) underlie this association. AGEs are cross-linked products that result from reactions between glucose and proteins. Little is known about the association between peripheral AGE concentration and cognitive aging. Methods: We prospectively studied 920 elders without dementia, 495 with diabetes and 425 with normal glucose (mean age 74.0 years). Using mixed models, we examined baseline AGE concentration, measured with urine pentosidine and analyzed as tertile, and performance on the Modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST) at baseline and repeatedly over 9 years. Incident cognitive impairment (a decline of >1.0 SD on each test) was analyzed with logistic regression. Results: Older adults with high pentosidine level had worse baseline DSST score (p=0.05) but not different 3MS score (p=0.32). On both tests, there was a more pronounced 9-year decline in those with high and mid pentosidine level compared to those in the lowest tertile (3MS 7.0, 5.4, and 2.5 point decline, p overall <0.001; DSST 5.9, 7.4, and 4.5 point decline, p=0.03). Incident cognitive impairment was higher in those with high or mid pentosidine level than those in the lowest tertile (3MS: 24% vs 17%, odds ratio=1.55; 95% confidence interval 1.07–2.26; DSST: 31% vs 22%, odds ratio=1.62; 95% confidence interval 1.13–2.33). There was no interaction between pentosidine level, diabetes status, and cognitive decline. Multivariate adjustment for age, sex, race, education, hypertension, cardiovascular disease, estimated glomerular filtration rate, and diabetes diminished results somewhat but overall patterns remained similar. Conclusion: High peripheral AGE level is associated with greater cognitive decline in older adults with and without diabetes.",
"title": "Advanced glycation end product level, diabetes, and accelerated cognitive aging"
},
{
"docid": "MED-2518",
"text": "Aging is not and cannot be programmed. Instead, aging is a continuation of developmental growth, driven by genetic pathways such as mTOR. Ironically, this is often misunderstood as a sort of programmed aging. In contrast, aging is a purposeless quasi-program or, figuratively, a shadow of actual programs. “The brightest flame casts the darkest shadow.” -George Martin",
"title": "Aging is not programmed"
},
{
"docid": "MED-1800",
"text": "Background Experimental and natural human adenovirus-36 (Adv36) infection of multiple animal species results in obesity through increasing adipogenesis and lipid accumulation in adipocytes. Presence of Adv36 antibodies detected by serum neutralization assay has previously been associated with obesity in children and adults living in the USA, South Korea and Italy, whereas no association with adult obesity was detected in Belgium/the Netherlands nor among USA military personnel. Adv36 infection has also been shown to reduce blood lipid levels, increase glucose uptake by adipose tissue and skeletal muscle biopsies, and to associate with improved glycemic control in non-diabetic individuals. Principal Findings Using a novel ELISA, 1946 clinically well-characterized individuals including 424 children and 1522 non-diabetic adults, and 89 anonymous blood donors, residing in central Sweden representing the population in Stockholm area, were studied for the presence of antibodies against Adv36 in serum. The prevalence of Adv36 positivity in lean individuals increased from ∼7% in 1992–1998 to 15–20% in 2002–2009, which paralleled the increase in obesity prevalence. We found that Adv36-positive serology was associated with pediatric obesity and with severe obesity in females compared to lean and overweight/mildly obese individuals, with a 1.5 to 2-fold Adv36 positivity increase in cases. Moreover, Adv36 positivity was less common among females and males on antilipid pharmacological treatment or with high blood triglyceride level. Insulin sensitivity, measured as lower HOMA-IR, showed a higher point estimate in Adv36-positive obese females and males, although it was not statistically significant (p = 0.08). Conclusion Using a novel ELISA we show that Adv36 infection is associated with pediatric obesity, severe obesity in adult females and lower risk of high blood lipid levels in non-diabetic Swedish individuals.",
"title": "Adenovirus-36 Is Associated with Obesity in Children and Adults in Sweden as Determined by Rapid ELISA"
},
{
"docid": "MED-2128",
"text": "BACKGROUND: Recipients of organ transplants are susceptible to Kaposi's sarcoma as a result of treatment with immunosuppressive drugs. Sirolimus (rapamycin), an immunosuppressive drug, may also have antitumor effects. METHODS: We stopped cyclosporine therapy in 15 kidney-transplant recipients who had biopsy-proven Kaposi's sarcoma and began sirolimus therapy. All patients underwent an excisional biopsy of the lesion and one biopsy of normal skin at the time of diagnosis. A second biopsy was performed at the site of a previous Kaposi's sarcoma lesion six months after sirolimus therapy was begun. We examined biopsy specimens for vascular endothelial growth factor (VEGF), Flk-1/KDR protein, and phosphorylated Akt and p70S6 kinase, two enzymes in the signaling pathway targeted by sirolimus. RESULTS: Three months after sirolimus therapy was begun, all cutaneous Kaposi's sarcoma lesions had disappeared in all patients. Remission was confirmed histologically in all patients six months after sirolimus therapy was begun. There were no acute episodes of rejection or changes in kidney-graft function. Levels of Flk-1/KDR and phosphorylated Akt and p70S6 kinase were increased in Kaposi's sarcoma cells. The expression of VEGF was increased in Kaposi's sarcoma cells and even more so in normal skin cells around the Kaposi's sarcoma lesions. CONCLUSIONS: Sirolimus inhibits the progression of dermal Kaposi's sarcoma in kidney-transplant recipients while providing effective immunosuppression. Copyright 2005 Massachusetts Medical Society.",
"title": "Sirolimus for Kaposi's sarcoma in renal-transplant recipients."
},
{
"docid": "MED-2115",
"text": "Dietary PUFA, mainly those of the n-3 family, are known to play essential roles in the maintenance of energy balance and in the reduction of body fat deposition through the upregulation of mitochondrial uncoupling that is the main source of reactive oxygen species. We hypothesized that rat supplementation with raw donkey's milk (DM), characterized by low-fat content and higher n3:n6 ratio, may affect energy balance, lipid metabolism, and prooxidant status as compared to animals treated with cow's milk. In the present study, the effects of drinking raw DM (for 4 weeks) on energy balance, lipid metabolism, antiinflammatory, and antioxidant/detoxifying defences was compared to that produced by rat intake of an iso-energetic amount of raw cow's milk. The hypolipidemic effect produced by DM paralleled with the enhanced mitochondrial activity/proton leakage and with the increased activity or expression of mitochondrial markers namely, carnitine palmitoyl transferase and uncoupling protein 2. The association of decreased energy efficiency with reduced proinflammatory signs (TNF-α and LPS levels) with the significant increase antioxidant (total thiols) and detoxifying enzyme activities (glutathione-S-transferase NADH quinone oxidoreductase) in DM-treated animals, indicated that beneficial effects were attributable, at least in part, to the activation of nuclear factor 2 erythroid-related factor 2 pathway. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",
"title": "Diet supplementation with donkey milk upregulates liver mitochondrial uncoupling, reduces energy efficiency and improves antioxidant and antiinflam..."
},
{
"docid": "MED-5240",
"text": "Endogenous advanced glycation endproducts (AGEs) include chemically crosslinking species (glycotoxins) that contribute to the vascular and renal complications of diabetes mellitus (DM). Renal excretion of the catabolic products of endogenous AGEs is impaired in patients with diabetic or nondiabetic kidney disease (KD). The aim of this study was to examine the oral absorption and renal clearance kinetics of food AGEs in DM with KD and whether circulating diet-derived AGEs contain active glycotoxins. Thirty-eight diabetics (DM) with or without KD and five healthy subjects (NL) received a single meal of egg white (56 g protein), cooked with (AGE-diet) or without fructose (100 g) (CL-diet). Serum and urine samples, collected for 48 hr, were monitored for AGE immunoreactivity by ELISA and for AGE-specific crosslinking reactivity, based on complex formation with 125I-labeled fibronectin. The AGE-diet, but not the CL-diet, produced distinct elevations in serum AGE levels in direct proportion to amount ingested (r = 0.8, P < 0.05): the area under the curve for serum (≈10% of ingested AGE) correlated directly with severity of KD; renal excretion of dietary AGE, although normally incomplete (only ≈30% of amount absorbed), in DM it correlated inversely with degree of albuminuria, and directly with creatinine clearance (r = 0.8, P < 0.05), reduced to <5% in DM with renal failure. Post-AGE-meal serum exhibited increased AGE-crosslinking activity (two times above baseline serum AGE, three times above negative control), which was inhibited by aminoguanidine. In conclusion, (i) the renal excretion of orally absorbed AGEs is markedly suppressed in diabetic nephropathy patients, (ii) daily influx of dietary AGEs includes glycotoxins that may constitute an added chronic risk for renal-vascular injury in DM, and (iii) dietary restriction of AGE food intake may greatly reduce the burden of AGEs in diabetic patients and possibly improve prognosis.",
"title": "Orally absorbed reactive glycation products (glycotoxins): An environmental risk factor in diabetic nephropathy"
},
{
"docid": "MED-2505",
"text": "BACKGROUND: Relative risk estimates suggest that effective implementation of behaviors commonly advocated in preventive medicine should increase life expectancy, although there is little direct evidence. OBJECTIVE: To test the hypothesis that choices regarding diet, exercise, and smoking influence life expectancy. METHODS: A total of 34 192 California Seventh-Day Adventists (75% of those eligible) were enrolled in a cohort and followed up from 1976 to 1988. A mailed questionnaire provided dietary and other exposure information at study baseline. Mortality for all subjects was ascertained by matching to state death tapes and the National Death Index. RESULTS: California Adventists have higher life expectancies at the age of 30 years than other white Californians by 7.28 years (95% confidence interval, 6.59-7.97 years) in men and by 4.42 years (95% confidence interval, 3.96-4.88 years) in women, giving them perhaps the highest life expectancy of any formally described population. Commonly observed combinations of diet, exercise, body mass index, past smoking habits, and hormone replacement therapy (in women) can account for differences of up to 10 years of life expectancy among Adventists. A comparison of life expectancy when these factors take high-risk compared with low-risk values shows independent effects that vary between 1.06 and 2.74 years for different variables. The effect of each variable is assessed with all others at either medium- or high-risk levels. CONCLUSIONS: Choices regarding diet, exercise, cigarette smoking, body weight, and hormone replacement therapy, in combination, appear to change life expectancy by many years. The longevity experience of Adventists probably demonstrates the beneficial effects of more optimal behaviors.",
"title": "Ten years of life: Is it a matter of choice?"
},
{
"docid": "MED-1433",
"text": "Advanced glycation end products (AGEs) are a heterogeneous, complex group of compounds that are formed when reducing sugar reacts in a non-enzymatic way with amino acids in proteins and other macromolecules. This occurs both exogenously (in food) and endogenously (in humans) with greater concentrations found in older adults. While higher AGEs occur in both healthy older adults and those with chronic diseases, research is progressing to both quantify AGEs in food and in people, and to identify mechanisms that would explain why some human tissues are damaged, and others are not. In the last twenty years, there has been increased evidence that AGEs could be implicated in the development of chronic degenerative diseases of aging, such as cardiovascular disease, Alzheimer’s disease and with complications of diabetes mellitus. Results of several studies in animal models and humans show that the restriction of dietary AGEs has positive effects on wound healing, insulin resistance and cardiovascular diseases. Recently, the effect of restriction in AGEs intake has been reported to increase the lifespan in animal models. This paper will summarize the work that has been published for both food AGEs and in vivo AGEs and their relation with aging, as well as provide suggestions for future research.",
"title": "Dietary Advanced Glycation End Products and Aging"
},
{
"docid": "MED-3309",
"text": "The human APOBEC3G protein is an innate anti-viral factor that can dominantly inhibit the replication of some endogenous and exogenous retroviruses. The prospects of purposefully harnessing such an anti-viral defense are under investigation. Here, long-term co-culture experiments were used to show that porcine endogenous retrovirus (PERV) transmission from pig to human cells is reduced to nearly undetectable levels by expressing human APOBEC3G in virus-producing pig kidney cells. Inhibition occurred by a deamination-independent mechanism, likely after particle production but before the virus could immortalize by integration into human genomic DNA. PERV inhibition did not require the DNA cytosine deaminase activity of APOBEC3G and, correspondingly, APOBEC3G-attributable hypermutations were not detected. In contrast, over-expression of the sole endogenous APOBEC3 protein of pigs failed to interfere significantly with PERV transmission. Together, these data constitute the first proof-of-principle demonstration that APOBEC3 proteins can be used to fortify the innate anti-viral defenses of cells to prevent the zoonotic transmission of an endogenous retrovirus. These studies suggest that human APOBEC3G-transgenic pigs will provide safer, PERV-less xenotransplantation resources and that analogous cross-species APOBEC3-dependent restriction strategies may be useful for thwarting other endogenous as well as exogenous retrovirus infections.",
"title": "The Restriction of Zoonotic PERV Transmission by Human APOBEC3G"
},
{
"docid": "MED-4431",
"text": "BACKGROUND: Workers in poultry plants have high exposure to a variety of transmissible agents present in poultry and their products. Subjects in the general population are also exposed. It is not known whether many of these agents cause disease in humans. If they do, we reason this would be readily evident in a highly exposed group such as poultry workers. We report here on mortality from non-malignant diseases in a cohort of poultry workers. METHODS: Mortality was compared with that of the US general population, and with that of a comparison group from the same union. Risk was estimated by standardized mortality ratio, proportional mortality ratio, and directly standardized risk ratio. RESULTS: Poultry workers as a group had an overall excess of deaths from diabetes, anterior horn disease, and hypertensive disease, and a deficit of deaths from intracerebral hemorrhage. Deaths from zoonotic bacterial diseases, helminthiasis, myasthenia gravis, schizophrenia, other diseases of the spinal cord, diseases of the esophagus and peritonitis were non-significantly elevated overall by all analyses, and significantly so in particular race/sex subgroups. CONCLUSIONS: Poultry workers may have excess occurrence of disease affecting several organs and systems, probably originating from widespread infection with a variety of microorganisms. The results for neurologic diseases could well represent important clues to the etiology of these diseases in humans. The small numbers of deaths involved in some cases limit interpretation.",
"title": "Mortality in the Baltimore union poultry cohort: non-malignant diseases."
},
{
"docid": "MED-3305",
"text": "BACKGROUND AND AIM: The occurrence of malignant pleural mesothelioma (MPM) has been reported among population groups with no documented professional exposure to asbestos fibres living in different geographic areas. This paper reviews existing data related to non occupational MPM including its occurrence in the province of Catania (Sicily, Italy). METHODS: An electronic search of literature related to non occupational MPM was performed including the year 2005. RESULTS: Non occupational MPM in subjects living in areas contaminated by a variety of asbestos and non asbestos fibres has been well documented through a number of epidemiologic studies including cases series, case-control studies, and a cohort study. In addition, the observation of familial clustering of MPM, suggests that genetic factors may play a role in the pathogenesis of this malignancy. The epidemiological evidence also suggests that MPM may occur as a result of the interaction between environmental carcinogens, genetic factors, and virus infection. CONCLUSION: It is likely that genetic predisposition and non-occupational exposure to low doses of asbestos and asbestos-like fibres may concur to the development of malignant mesothelioma. However, additional epidemiological and laboratory studies are needed to further understand the relationship between environmental exposure and individual susceptibility to this malignancy.",
"title": "Non-occupational malignant pleural mesothelioma due to asbestos and non-asbestos fibres."
},
{
"docid": "MED-1808",
"text": "BACKGROUND: Human adenovirus-36 (Ad-36) is thought to induce obesity by a direct effect of the viral E4orf1 gene on lipogenic enzymes in host adipocytes. Ad-36 prevalence is 30% in obese adults, but prevalence has not been reported in childhood obesity. OBJECTIVES: To determine the prevalence of Ad-36 infection in obese Korean children (age 14.8 +/- 1.9; range 8.3-6.3 years); correlation of infection with BMI z-score and other obesity measures. METHODS: Blood was drawn at the annual school physical exam or clinic visit; Ad-36 status was determined by serum neutralization assay; and routine serum chemistry values. RESULTS: A total of 30% of subjects were positive (N = 25) for Ad-36; 70% were negative (N = 59). Significantly higher BMI z-scores (1.92 vs. 1.65, p < 0.01) and waist circumferences (96.3 vs. 90.7 cm, p = 0.05) were found in infected versus uninfected children. Cardiovascular risk factors were not significantly different. CONCLUSIONS: Ad-36 infection is common in obese Korean children and correlates highly with obesity. Ad-36 may have played a role in the obesity and Type 2 diabetes epidemic in children.",
"title": "Human adenovirus-36 antibody status is associated with obesity in children."
},
{
"docid": "MED-2132",
"text": "The mammalian target of rapamycin (mTOR) is a protein kinase that plays key roles in cellular regulation. It forms complexes with additional proteins. The best-understood one is mTOR complex 1 (mTORC1). The regulation and cellular functions of mTORC1 have been the subjects of intense study; despite this, many questions remain to be answered. They include questions about the actual mechanisms by which mTORC1 signaling is stimulated by hormones and growth factors, which involves the small GTPase Rheb, and by amino acids, which involves other GTPase proteins. The control of Rheb and the mechanism by which it activates mTORC1 remain incompletely understood. Although it has been known for many years that rapamycin interferes with some functions of mTORC1, it is not known how it does this, or why only some functions of mTORC1 are affected. mTORC1 regulates diverse cellular functions. Several mTORC1 substrates are now known, although in several cases their physiological roles are poorly or incompletely understood. In the case of several processes, although it is clear that they are regulated by mTORC1, it is not known how mTORC1 does this. Lastly, mTORC1 is implicated in ageing, but again it is unclear what mechanisms account for this. Given the importance of mTORC1 signaling both for cellular functions and in human disease, it is a high priority to gain further insights into the control of mTORC1 signaling and the mechanisms by which it controls cellular functions and animal physiology.",
"title": "mTORC1 signaling: what we still don't know."
},
{
"docid": "MED-1432",
"text": "Sirtuins (SIRTs), a family of nicotinamide adenine dinucleotide (NAD)-dependent deacetylases, are emerging as key molecules that regulate aging and age-related diseases including cancers, metabolic disorders, and neurodegenerative diseases. Seven isoforms of SIRT (SIRT1–7) have been identified in mammals. SIRT1 and 6, mainly localized in the nucleus, regulate transcription of genes and DNA repair. SIRT3 in the mitochondria regulates mitochondrial bioenergetics. Initial studies in yeasts, nematodes, and flies indicated a strong connection of SIRT with the life-prolonging effects of calorie restriction (CR), a robust experimental intervention for longevity in a range of organisms. However, subsequent studies reported controversial findings regarding SIRT roles in the effect of CR. This review describes the functional roles of mammalian SIRTs and discusses their relevance to mechanisms underlying the longevity effect of CR.",
"title": "Do Sirtuins Promote Mammalian Longevity?: A Critical Review on Its Relevance to the Longevity Effect Induced by Calorie Restriction"
},
{
"docid": "MED-1438",
"text": "Background Advanced glycations end products increase oxidant stress, inflammation, and neurotoxicity. Serum levels are increased in diabetes and aging. We examined the relationship between serum methylglyoxal derivatives (sMG), and cognitive decline, in 267 non-demented elderly. Methods Tobit mixed regression models assessed the association of baseline sMG with cognitive decline in the Mini Mental State Exam (MMSE) over time, controlling for sociodemographic factors (age, sex, and years of education), cardiovascular risk factors (diabetes and presence of an APOE4 allele), and kidney function. sMG was assessed by ELISA. Results The fully adjusted model showed an annual decline of 0.26 MMSE points per unit increase in baseline sMG (p=0.03). Significance was unchanged as additional risk factors were added to the model. The interactions of sMG with diabetes, sex, age, kidney function, and APOE4 genotype were not significant. Conclusions Higher levels of baseline sMG were associated with a faster rate of cognitive decline, after adjusting for several sociodemographic and clinical characteristics. This relationship did not differ by sex, APOE4 genotype, or diabetes status suggesting its generality. Since subjects were cognitively normal at the beginning of the study, elevated sMG may be indicative of brain cell injury initiated before clinically evident cognitive compromise.",
"title": "Serum concentration of an inflammatory glycotoxin, methylglyoxal, is associated with increased cognitive decline in elderly individuals"
},
{
"docid": "MED-2385",
"text": "The purpose of this investigation was to estimate the total hair mercury of diseased people (not including patients of mercury poisoning such as Minamata disease). Hair samples were collected from 133 diseased volunteers in Tokyo and the surrounding areas from Oct. 1992 to June 1993. The total mercury concentrations in the hair of ordinary diseased people (atopic dermatitis, asthma, dementia, cerebral infarct, osteoporosis, hypertension and diabetes) were from 2.08 ppm to 36.5 ppm. Those values were considerably higher than that of healthy people of the same age groups. However, the uptake routes and the metabolic mechanism of high hair mercury concentrations in diseased people are not clear.",
"title": "Concentration of mercury in hair of diseased people in Japan."
},
{
"docid": "MED-3311",
"text": "OBJECTIVES: We studied mortality in two separate cohorts of workers in abattoirs (N=4996) and meat processing plants (N=3642) belonging to a meatcutters' union, because they were exposed to viruses that cause cancer in food animals, and also to chemical carcinogens at work. METHODS: Standardized mortality ratios (SMRs) and proportional mortality ratios (PMRs) were estimated for each cohort as a whole and in subgroups defined by race and sex, using the US general population mortality rates for comparison. Study subjects were followed up from January 1950 to December 2006, during which time over 60% of them died. RESULTS: An excess of deaths from cancers of the base of the tongue, esophagus, lung, skin, bone and bladder, lymphoid leukemia, and benign tumors of the thyroid and other endocrine glands, and possibly Hodgkin's disease, was observed in abattoir and meat processing workers. Significantly lower SMRs were recorded for cancer of the thymus, mediastinum, pleura, etc., breast cancer, and non-Hodgkin's lymphoma. CONCLUSION: This study confirms the excess occurrence of cancer in workers in abattoirs and meat processing plants, butchers, and meatcutters, previously reported in this cohort and other similar cohorts worldwide. Large nested case-control studies are now needed to examine which specific occupational and non-occupational exposures are responsible for the excess. There is now sufficient evidence for steps to be taken to protect workers from carcinogenic exposures at the workplace. There are also serious implications for the general population which may also be exposed to some of these viruses. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Cancer mortality in workers employed in cattle, pigs, and sheep slaughtering and processing plants."
},
{
"docid": "MED-1440",
"text": "Aging and metabolism-related disorders are risk factors for Alzheimer disease (AD). Since sirtuins may increase the lifespan through regulation of cellular metabolism, we compared the concentration of sirtuin 1 (SIRT1) in the brains of AD patients (n = 19) and controls (n = 22) using Western immunoblots and in situ hybridization. We report a significant reduction of SIRT1 (mRNA: −29%; protein: −45%) in the parietal cortex of AD patients, but not in the cerebellum. Further analyses in a second cohort of 36 subjects confirmed that cortical SIRT1 was decreased in the cortex of AD patients but not in individuals with mild cognitive impairment. SIRT1 mRNA and its translated protein correlated negatively with the duration of symptoms (mRNA: r2 = −0.367; protein: r2 = −0.326) and the accumulation of paired helical filament tau (mRNA: r2 = −0.230; protein: r2 = −0.119), but weakly with insoluble amyloid-β(Aβ42 (mRNA: r2 = −0.090; protein: r2 = −0.072). A significant relationship between SIRT1 levels and global cognition scores proximate to death was also found (r2 = +0.09; p = 0.049). In contrast, cortical SIRT1 levels remained unchanged in a triple-transgenic animal model of AD. Collectively, our results indicate that loss of SIRT1 is closely associated with the accumulation of Aβ and tau in the cerebral cortex of patients with AD.",
"title": "SIRT1 Decrease Parallels the Accumulation of tau in Alzheimer Disease"
},
{
"docid": "MED-2521",
"text": "A streptomycete was isolated from an Easter Island soil sample and found to inhibit Candida albicans, Microsporum gypseum and Trichophyton granulosum. The antibiotic-producing microorganism was characterized and identified as Streptomyces hygroscopicus. The antifungal principle was extracted with organic solvent from the mycelium, isolated in crystalline form and named rapamycin. Rapamycin is mainly active against Candida albicans; minimum inhibitory concentration against ten strains ranged from 0.02 to 0.2 mug/ml. Its apparent activity against Microsporum gypseum and Trichophyton granulosum is lower because of its instability in culture media on prolonged incubation required by these fungi. No activity was observed against gram-positive and gram-negative bacteria. Acute toxicity in mice is low.",
"title": "Rapamycin (AY-22,989), a new antifungal antibiotic. I. Taxonomy of the producing streptomycete and isolation of the active principle."
},
{
"docid": "MED-2512",
"text": "Ageing is a challenge for any living organism and human longevity is a complex phenotype. With increasing life expectancy, maintaining long-term health, functionality and well-being during ageing has become an essential goal. To increase our understanding of how ageing works, it may be advantageous to analyze the phenotype of centenarians, perhaps one of the best examples of successful ageing. Healthy ageing involves the interaction between genes, the environment, and lifestyle factors, particularly diet. Besides evaluating specific gene-environment interactions in relation to exceptional longevity, it is important to focus attention on modifiable lifestyle factors such as diet and nutrition to achieve extension of health span. Furthermore, a better understanding of human longevity may assist in the design of strategies to extend the duration of optimal human health. In this article we briefly discuss relevant topics on ageing and longevity with particular focus on dietary patterns of centenarians and nutrient-sensing pathways that have a pivotal role in the regulation of life span. Finally, we also discuss the potential role of Nrf2 system in the pro-ageing signaling emphasizing its phytohormetic activation.",
"title": "Extending healthy ageing: nutrient sensitive pathway and centenarian population"
},
{
"docid": "MED-4433",
"text": "BACKGROUND: The role of zoonotic biological agents in human cancer occurrence has been little studied. Humans are commonly exposed to viruses that naturally infect and cause cancer in food animals such as poultry that constitute part of the biological environment. It is not known if these viruses cause cancer in humans. OBJECTIVE: To study cancer mortality in the largest cohort to date, of 20,132 workers in poultry slaughtering and processing plants, a group with the highest human exposures to these viruses. METHODS: Mortality in poultry workers was compared with that in the US general population through the estimation of standardized mortality ratios. RESULTS: Significantly increased risks were observed in the cohort as a whole or in subgroups, for several cancer sites, viz: cancers of the buccal cavity and pharynx; pancreas; trachea/bronchus/lung; brain; cervix; lymphoid leukemia; monocytic leukemia; and tumors of the hemopoietic and lymphatic systems. Elevated SMRs that were not statistically significant were observed for cancers of the liver, nasopharynx, myelofibrosis, and myeloma. New sites observed to be significantly in excess in this study were cancers of the cervix and penis. CONCLUSION: This large study provides evidence that a human group with high exposure to poultry oncogenic viruses has increased risk of dying from several cancers. Other occupational carcinogenic exposures could be of importance in explaining some of the findings, such as fumes from wrapping machines. These findings may have implications for public health amongst persons in the general population who may also be exposed to these viruses. What is needed now are epidemiologic studies that can demonstrate whether the excess of specific cancers can be attributed to specific occupational exposures while adequately controlling for other potential occupational and non-occupational carcinogenic exposures. Copyright 2010 Elsevier Inc. All rights reserved.",
"title": "Cancer mortality in poultry slaughtering/processing plant workers belonging to a union pension fund."
},
{
"docid": "MED-2400",
"text": "The early effects of 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) exposure in the population involved in the Seveso, Italy, incident in 1976, have been examined in numerous studies. Chloracne was the only effect linked with sufficient certainty to dioxin exposure. The possible long-term consequences were investigated with mortality and cancer incidence studies. Mortality and morbidity findings during the 20-year period following the accident showed increased risk from lymphoemopoietic neoplasm, digestive system cancer (rectum in males, and biliary tract among females, in particular) and respiratory system cancer (lung, among males). In the incidence analyses, also thyroid gland and pleura cancer appeared suggestively increased. Soft tissue sarcomas showed an increase in the largest, yet least exposed, exposure sub-cohort. Several hypotheses associating non-cancer effects with dioxin exposure were corroborated by findings in the Seveso population: this was the case with cardiovascular effects (possibly linked to both chemical exposure and stressful disaster experience), endocrine effects (diabetes among females) and reproductive effects: exposure of men to TCDD was linked to a lowered male/female sex ratio in their offspring. The results of many Seveso studies point to possible gender effects, in accordance with animal models. Notwithstanding the acknowledged study limitations (lack of individual exposure markers, short latency, and small population size for certain cancer types), results of previous experimental and epidemiological studies, along with mechanistic knowledge on dioxin toxicity, support the hypotheses that the observed excesses might be associated with dioxin exposure. The mortality and cancer incidence follow-up of the Seveso cohort are continuing.",
"title": "Short- and long-term morbidity and mortality in the population exposed to dioxin after the \"Seveso accident\"."
},
{
"docid": "MED-5234",
"text": "Diet is a major environmental source of proinflammatory AGEs (heat-generated advanced glycation end products); its impact in humans remains unclear. We explored the effects of two equivalent diets, one regular (high AGE, H-AGE) and the other with 5-fold lower AGE (L-AGE) content on inflammatory mediators of 24 diabetic subjects: 11 in a 2-week crossover and 13 in a 6-week study. After 2 weeks on H-AGE, serum AGEs increased by 64.5% (P = 0.02) and on L-AGE decreased by 30% (P = 0.02). The mononuclear cell tumor necrosis factor-α/β-actin mRNA ratio was 1.4 ± 0.5 on H-AGE and 0.9 ± 0.5 on L-AGE (P = 0.05), whereas serum vascular adhesion molecule-1 was 1,108 ± 429 and 698 ± 347 ng/ml (P = 0.01) on L- and H-AGE, respectively. After 6 weeks, peripheral blood mononuclear cell tumor necrosis factor-α rose by 86.3% (P = 0.006) and declined by 20% (P, not significant) on H- or L-AGE diet, respectively; C-reactive protein increased by 35% on H-AGE and decreased by 20% on L-AGE (P = 0.014), and vascular adhesion molecule-1 declined by 20% on L-AGE (P < 0.01) and increased by 4% on H-AGE. Serum AGEs were increased by 28.2% on H-AGE (P = 0.06) and reduced by 40% on L-AGE (P = 0.02), whereas AGE low density lipoprotein was increased by 32% on H-AGE and reduced by 33% on L-AGE diet (P < 0.05). Thus in diabetes, environmental (dietary) AGEs promote inflammatory mediators, leading to tissue injury. Restriction of dietary AGEs suppresses these effects.",
"title": "Inflammatory mediators are induced by dietary glycotoxins, a major risk factor for diabetic angiopathy"
},
{
"docid": "MED-4769",
"text": "Excessive fat accumulation has been observed in the field in chickens infected with adenovirus. In the present study this has been verified under experimental conditions. Chickens inoculated with adenovirus showed lesser weight gain but excessive adiposity compared to normal control chickens. These changes could not be explained by variation in food consumption. Chickens acquiring adenovirus naturally from the inoculated group showed similar adiposity. Serum cholesterol and triglyceride levels of inoculated and naturally infected chickens were significantly lower compared to those of the control group. Such an association between adenovirus infection and adiposity has been shown, probably, for the first time, which might help in further understanding of the complex problem of obesity.",
"title": "Effect of adenovirus infection on adiposity in chicken."
},
{
"docid": "MED-3295",
"text": "Background Few studies have investigated mortality in seafood workers worldwide, and no such study has been conducted in the United States. The objective of this study was to investigate mortality in American seafood workers. Methods The study population was derived from 4 states and consisted of 4116 subjects who worked mainly in seafood processing plants. They were followed up from 1966 to 2003. Standardized mortality ratios (SMRs) and proportional mortality ratios (PMRs) were estimated, using the US general population for comparison. Results About 45% of the cohort was born after 1949. A total of 788 deaths were recorded; 53% of the decedents were female, and 88% were white. The SMRs for stomach cancer and disorders of the thyroid gland in the cohort as a whole were 2.1 (95% confidence interval [CI], 1.1–3.8) and 6.1 (95% CI 1.3–18.0), respectively. The SMRs for breast cancer, and occlusion/stenosis of the pre-cerebral/cerebral arteries in the cohort as a whole were 0.5 (95% CI, 0.3–0.9) and 0.5 (95% CI, 0.2–0.8), respectively. The SMR for ischemic heart disease in white females was 0.8 (95% CI, 0.6–0.9). Conclusions This cohort had excess deaths from stomach cancer and disorders of the thyroid gland, and deficit of deaths from breast cancer, stroke and ischemic heart disease. The significance of these findings is unknown, especially as less than 20% of the cohort were deceased. Nevertheless, the cohort is unique and important, and further follow-up may shed more light on mortality patterns in this occupational group.",
"title": "Cancer and Noncancer Mortality Among American Seafood Workers"
},
{
"docid": "MED-3321",
"text": "Avian leukosis/sarcoma viruses (ALSV) infect and cause cancers in chickens. Poultry workers are exposed to ALSV and other infectious agents in the workplace. This study examines if industrial hygiene assessment of antibody levels in poultry workers can identify risky job tasks at the higher exposure risk to an infectious agent, i.e., ALSV. We compared ALSV antibody levels in poultry workers and control subjects. Occupational and demographical factors were examined for an association with the exposure risk in poultry workers. We found that the antibody levels were significantly higher in poultry workers than in control subjects. Job category and age together were significantly associated with the antibody levels in workers. Certain job tasks were identified with significantly higher antibody levels as compared to others, implying that recommendations should be made to protect workers at these jobs. The findings of this study indicate that the measurement of antibody levels in workers can be useful for industrial hygiene assessment of exposure to infectious agents.",
"title": "Occupational exposure assessment using antibody levels: exposure to avian leukosis/sarcoma viruses in the poultry industry."
},
{
"docid": "MED-2117",
"text": "Recent evidence underlines the role of Western diet in the pathogenesis of acne. Acne is absent in populations consuming Palaeolithic diets with low glycaemic load and no consumption of milk or dairy products. Two randomized controlled studies, one of which is presented in this issue of Acta Dermato-Venereologica, have provided evidence for the beneficial therapeutic effects of low glycaemic load diets in acne. Epidemiological evidence confirms that milk consumption has an acne-promoting or acne-aggravating effect. Recent progress in understanding the nutrient-sensitive kinase mammalian target of rapamycin complex 1 (mTORC1) allows a new view of nutrient signalling in acne by both high glycaemic load and increased insulin-, IGF-1-, and leucine signalling due to milk protein consumption. Acne should be regarded as an mTORC1-driven disease of civilization, like obesity, type 2 diabetes and cancer induced by Western diet. Early dietary counselling of teenage acne patients is thus a great opportunity for dermatology, which will not only help to improve acne but may reduce the long-term adverse effects of Western diet on more serious mTORC1-driven diseases of civilization.",
"title": "Diet in acne: further evidence for the role of nutrient signalling in acne pathogenesis."
},
{
"docid": "MED-2519",
"text": "To date, the only intervention that has consistently been shown to slow the rate of aging, and to increase mean and maximum lifespan in short-lived species, is life-long calorie restriction. It is yet unclear whether long-term calorie restriction in longer lived species (i.e. primates and humans) will have a similar effect. In humans, several studies investigating short-term calorie restriction or \"weight loss\" programs suggest beneficial outcomes on parameters of cardiovascular disease. Studies on long-term calorie restriction are performed on a self-selected group of human subjects and show similar effects. However, few studies are currently investigating the quality of life and potential pitfalls of long-term calorie restriction in humans. It is likely that some of the physiological and psychological effects of caloric restriction that occur in animals may impact the human life very differently. For certain, calorie restriction has a plethora of health benefits in mammals, such as a reduction in age-related diseases such as cancer. However, despite the \"magic\" of CR, this intervention in humans may present itself with a number of health concerns, which may not be applicable to or impact the life of experimental animals, but may do so in humans. These potential pitfalls and \"side effects\" are not clearly addressed in the literature and will be a focus of this review.",
"title": "Caloric restriction in humans: potential pitfalls and health concerns."
},
{
"docid": "MED-2513",
"text": "Over the last several years, new evidence has kept pouring in about the remarkable effect of caloric restriction (CR) on the conspicuous bedfellows- aging and cancer. Through the use of various animal models, it is now well established that by reducing calorie intake one can not only increase life span but, also, lower the risk of various age related diseases such as cancer. Cancer cells are believed to be more dependent on glycolysis for their energy requirements than normal cells and, therefore, can be easily targeted by alteration in the energy-metabolic pathways, a hallmark of CR. Apart from inhibiting the growth of transplantable tumors, CR has been also shown to inhibit the development of spontaneous, radiation, and chemically induced tumors. The question regarding the potentiality of the anti-tumor effect of CR in humans has been in part answered by the resistance of a cohort of women, who had suffered from anorexia in their early life, to breast cancer. However, human research on the beneficial effect of CR is still at an early stage and needs further validation. Though the complete mechanism of the anti-tumor effect of CR is far from clear, the plausible involvement of nutrient sensing pathways or IGF-1 pathways proposed for its anti-aging action cannot be overruled. In fact, cancer cell lines, mutant for proteins involved in IGF-1 pathways, failed to respond to CR. In addition, CR decreases the levels of many growth factors, anabolic hormones, inflammatory cytokines, and oxidative markers that are deregulated in several cancers. In this review, we discuss the anti-tumor effect of CR, describing experiments done in vitro in tumor models and in vivo in mouse models in which the tumor was induced by means of radiation or chemical exposure, expressing oncogenes or deleting tumor suppression genes. We also discuss the proposed mechanisms of CR anti-tumor action. Lastly, we argue the necessity of gene expression studies in cancerous versus normal cells upon CR.",
"title": "Insights into the beneficial effect of caloric/ dietary restriction for a healthy and prolonged life"
},
{
"docid": "MED-3306",
"text": "OBJECTIVES: Occupation as a farmer has been associated with increased risks of haematological cancers in adults. This study aimed to examine whether farm exposures in childhood contribute to these risks, by using parental occupation in farming as a proxy for growing up on a farm. METHODS: New Zealand death records (1998-2003) of persons aged 35-85 were extracted (n=114 289). For 82.3% usual occupation and the occupation of at least one of the parents could be coded (n=94 054). Unconditional logistic regression analyses included 3119 haematological cancer deaths (cases) and 90 935 deaths from other causes (controls). ORs for farming and growing up on a farm were adjusted for each other, year of birth, age at death, socio-economic status, Māori ethnicity, immigration status and sex. RESULTS: Growing up on a livestock farm was positively associated with haematological cancer (OR 1.22, 95% CI 1.05 to 1.41), particularly for poultry farms (OR 2.99, 95% CI 1.44 to 6.21), while growing up on a crop farm was not (OR 0.81, 95% CI 0.64 to 1.03). Crop farming in adulthood was associated with an increased haematological cancer risk (OR 1.49, 95% CI 1.13 to 1.96), while livestock farming was not (OR 0.80, 95% CI 0.63 to 1.00), except for beef cattle farming (OR 2.99, 95% CI 1.28 to 7.00). These results did not change appreciably when different control groups with different causes of death were used. CONCLUSIONS: These results could suggest a role for early life biological exposures in the development of haematological cancers.",
"title": "Farming, growing up on a farm, and haematological cancer mortality."
},
{
"docid": "MED-4553",
"text": "Alzheimer's disease (AD) is the most common dementing disorder of late life. Although there might be various different triggering events in the early stages of the disease, they seem to converge on a few characteristic final pathways in the late stages, characterized by inflammation and neurodegeneration. In this review, we put forward the hypothesis that advanced glycation end products (AGEs) and their precursors, including methylglyoxal, are both biomarkers and causative agents (\"gerontotoxins\") characteristic for this disorder. Accumulation of AGEs is a normal feature of aging, but is accelerated in AD, where AGEs can be detected in amyloid plaques and neurofibrillary tangles. AGE modification may explain many of the neuropathological and biochemical features of AD such as extensive protein cross-linking, inflammation, oxidative stress and neuronal cell death. We suggest that methylglyoxal is one of the major carbonyl species responsible for the formation of AGEs. We propose that one promising pharmacological approach to prevent the formation of AGEs would be to lower the methylglyoxal concentration. This can be achieved, for example, by decreasing the concentration of methylglyoxal precursors such as d-glyceraldehyde-3-phosphate by allowing a higher flux through the pentose phosphate pathway or by increasing methylglyoxal detoxification through the glyoxalase system. Alternatively, methylglyoxal could be scavenged by various types of carbonyl scavengers. Copyright © 2010 Elsevier Inc. All rights reserved.",
"title": "Advanced glycation end products as biomarkers and gerontotoxins - A basis to explore methylglyoxal-lowering agents for Alzheimer's disease?"
},
{
"docid": "MED-2404",
"text": "Background Epidemiologic studies suggest that there may be an association between environmental exposure to persistent organic pollutants (POPs) and diabetes. Objective The aim of this study was to test the hypothesis that residential proximity to POP-contaminated waste sites result in increased rates of hospitalization for diabetes. Methods We determined the number of hospitalized patients 25–74 years of age diagnosed with diabetes in New York State exclusive of New York City for the years 1993–2000. Descriptive statistics and negative binomial regression were used to compare diabetes hospitalization rates in individuals who resided in ZIP codes containing or abutting hazardous waste sites containing POPs (“POP” sites); ZIP codes containing hazardous waste sites but with wastes other than POPs (“other” sites); and ZIP codes without any identified hazardous waste sites (“clean” sites). Results Compared with the hospitalization rates for diabetes in clean sites, the rate ratios for diabetes discharges for people residing in POP sites and “other” sites, after adjustment for potential confounders were 1.23 [95% confidence interval (CI), 1.15–1.32] and 1.25 (95% CI, 1.16–1.34), respectively. In a subset of POP sites along the Hudson River, where there is higher income, less smoking, better diet, and more exercise, the rate ratio was 1.36 (95% CI, 1.26–1.47) compared to clean sites. Conclusions After controlling for major confounders, we found a statistically significant increase in the rate of hospitalization for diabetes among the population residing in the ZIP codes containing toxic waste sites.",
"title": "Increased Rate of Hospitalization for Diabetes and Residential Proximity of Hazardous Waste Sites"
},
{
"docid": "MED-2130",
"text": "In metazoans, TOR is an essential protein that functions as a master regulator of cellular growth and proliferation. Over the past decade, there has been an explosion of information about this critical master kinase, ranging from the composition of the TOR protein complex to its ability to act as an integrator of numerous extracellular signals. Unfortunately, this plethora of information has also raised numerous questions regarding TOR function. Currently, the prevailing view is that mammalian TOR (mTOR) exists in at least two molecular complexes, mTORC1 and mTORC2, which are largely defined by the presence of either RAPTOR or RICTOR. However, additional co-factors have been identified for each complex, and their importance in mediating mTOR signals has been incompletely elucidated. Similarly, there are differences in mTOR function that reflect the tissue of origin. In this review, we present an alternative view to mTOR complex formation and function, which envisions mTOR regulation and signal propagation as a reflection of cell type- and basal state-dependent conditions. The re-interpretation of mTOR biology in this framework may facilitate the design of therapies most likely to effectively inhibit this central regulator of cell behavior.",
"title": "Deconvoluting mTOR biology"
},
{
"docid": "MED-3315",
"text": "PURPOSE: To test the hypothesis that exposure to poultry oncogenic viruses that widely occurs occupationally in poultry workers and in the general population, may be associated with increased risks of deaths from liver and pancreatic cancers, and to identify new risk factors. METHODS: A pilot case-cohort study of both cancers within a combined cohort of 30,411 highly exposed poultry workers and 16,408 control subjects was conducted, and risk assessed by logistic regression odds ratios (OR) and proportional hazards risk ratios. RESULTS: New occupational findings were recorded respectively for pancreatic/liver cancers, for slaughtering of poultry (OR = 8.9, 95% confidence interval [CI]: 2.7-29.3)/OR = 9.1, 95% CI: 1.9-42.9); catching of live chickens (OR = 3.6, 95% CI: 1.2-10.9)/OR = 1.0, 95% CI: 0.1-8.5); killing other types of animals for food (OR = 4.8, 95% CI: 1.5-16.6)/OR = 2.0, 95% CI: 0.2-18.2), and ever worked on a pig raising farm (OR = 3.0, 95% CI: 1.0-8.2) for pancreatic cancer only. New non-occupational findings for liver cancer were for receiving immunization with yellow fever vaccine (OR = 8.7, 95% CI: 1.0-76.3); and vaccination with typhoid vaccine (OR = 6.3, 95% CI: 1.1-37.4). The study also confirmed previously reported risk factors for both diseases. CONCLUSIONS: This study provides preliminary evidence that exposure to poultry oncogenic viruses may possibly be associated with the occurrence of liver and pancreatic cancers. Case-control studies nested within occupational cohorts of highly exposed subjects of sufficient statistical power may provide an efficient and valid method of investigating/confirming these findings. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "A pilot case-cohort study of liver and pancreatic cancers in poultry workers."
},
{
"docid": "MED-1435",
"text": "Age-related loss of brain tissue has been inferred from cross-sectional neuroimaging studies, but direct measurements of gray and white matter changes from longitudinal studies are lacking. We quantified longitudinal magnetic resonance imaging (MRI) scans of 92 nondemented older adults (age 59-85 years at baseline) in the Baltimore Longitudinal Study of Aging to determine the rates and regional distribution of gray and white matter tissue loss in older adults. Using images from baseline, 2 year, and 4 year follow-up, we found significant age changes in gray (p < 0.001) and white (p < 0.001) volumes even in a subgroup of 24 very healthy elderly. Annual rates of tissue loss were 5.4 +/- 0.3, 2.4 +/- 0.4, and 3.1 +/- 0.4 cm3 per year for total brain, gray, and white volumes, respectively, and ventricles increased by 1.4 +/- 0.1 cm3 per year (3.7, 1.3, 2.4, and 1.2 cm3, respectively, in very healthy). Frontal and parietal, compared with temporal and occipital, lobar regions showed greater decline. Gray matter loss was most pronounced for orbital and inferior frontal, cingulate, insular, inferior parietal, and to a lesser extent mesial temporal regions, whereas white matter changes were widespread. In this first study of gray and white matter volume changes, we demonstrate significant longitudinal tissue loss for both gray and white matter even in very healthy older adults. These data provide essential information on the rate and regional pattern of age-associated changes against which pathology can be evaluated and suggest slower rates of brain atrophy in individuals who remain medically and cognitively healthy.",
"title": "Longitudinal magnetic resonance imaging studies of older adults: a shrinking brain."
},
{
"docid": "MED-1803",
"text": "WHO has declared obesity to be a global epidemic. Obesity management strategies mainly target behavioural components of the disorder, but are only marginally effective. A comprehensive understanding of the causative factors of obesity might provide more effective management approaches. Several microbes are causatively and correlatively linked with obesity in animals and human beings. If infections contribute to human obesity, then entirely different prevention and treatment strategies and public health policies could be needed to address this subtype of the disorder. Ethical reasons preclude experimental infection of human beings with candidate microbes to unequivocally determine their contribution to obesity. As an alternative, the available information about the adipogenic human adenovirus Ad36 has been used to create a template that can be used to examine comprehensively the contributions of specific candidate microbes to human obesity. Clinicians should be aware of infectobesity (obesity of infectious origin), and its potential importance in effective obesity management. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "A framework for identification of infections that contribute to human obesity."
},
{
"docid": "MED-2501",
"text": "Amino acids play fundamental roles in the cell both as the building blocks of new proteins and as metabolic precursors. To adapt to their limitation during periods of protein starvation, multiple adaptive mechanisms have evolved, including a rapid cessation of new protein synthesis, an increase in amino acid biosynthesis and transport, and autophagy. Here, we discuss what we currently know about how amino acid limitation is sensed, and how this sensing might be transmitted to mTORC1 to regulate protein synthesis and autophagy. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Amino acid sensing and regulation of mTORC1."
},
{
"docid": "MED-2134",
"text": "Proteins regulating the mammalian target of rapamycin (mTOR), as well as some of the targets of the mTOR kinase, are overexpressed or mutated in cancer. Rapamycin, the naturally occurring inhibitor of mTOR, along with a number of recently developed rapamycin analogs (rapalogs) consisting of synthetically derived compounds containing minor chemical modifications to the parent structure, inhibit the growth of cell lines derived from multiple tumor types in vitro, and tumor models in vivo. Results from clinical trials indicate that the rapalogs may be useful for the treatment of subsets of certain types of cancer. The sporadic responses from the initial clinical trials, based on the hypothesis of general translation inhibition of cancer cells are now beginning to be understood owing to a more complete understanding of the dynamics of mTOR regulation and the function of mTOR in the tumor microenvironment. This review will summarize the preclinical and clinical data and recent discoveries of the function of mTOR in cancer and growth regulation.",
"title": "mTOR and cancer therapy."
},
{
"docid": "MED-4728",
"text": "Over the last two decades, the incidence of obesity and associated metabolic syndrome diseases has risen dramatically, becoming a global health crisis. Increased caloric intake and decreased physical activity are believed to represent the root causes of this dramatic rise. However, recent findings highlight the possible involvement of environmental obesogens, xenobiotic chemicals that can disrupt the normal developmental and homeostatic controls over adipogenesis and energy balance. Environmental estrogens, i.e. chemicals with estrogenic potential, have been reported to perturb adipogenic mechanisms using in vitro model systems, but other classes of endocrine-disrupting chemicals are now coming under scrutiny as well. Organotins represent one class of widespread persistent organic pollutants with potent endocrine-disrupting properties in both invertebrates and vertebrates. New data identify tributyltin chloride and triphenyltin chloride as nanomolar agonist ligands for retinoid X receptor (RXR alpha, RXR beta, and RXR gamma) and peroxisome proliferator-activated receptor gamma, nuclear receptors that play pivotal roles in lipid homeostasis and adipogenesis. The environmental obesogen hypothesis predicts that inappropriate receptor activation by organotins will lead directly to adipocyte differentiation and a predisposition to obesity and/or will sensitize exposed individuals to obesity and related metabolic disorders under the influence of the typical high-calorie, high-fat Western diet. The linking of organotin exposure to adipocyte differentiation and obesity opens an important new area of research into potential environmental influences on human health and disease.",
"title": "Environmental obesogens: organotins and endocrine disruption via nuclear receptor signaling."
},
{
"docid": "MED-1439",
"text": "BACKGROUND AND PURPOSE: The purpose of this study is to investigate the longitudinal age-related changes in human brain volume using stereological methods. METHODS: Sixty-six older participants (34 men, 32 women, age [mean +/- SD] 78.9 +/- 3.3 years, range 74-87 years) with normal baseline and follow-up examinations underwent 2 MRIs (magnetic resonance imaging) of the brain on average 4.4 years apart. The volumes of the cerebrum (defined as cortex, basal ganglia, thalamus, and white matter), lateral ventricles, and cerebellum were estimated on the 2 MRIs using an unbiased stereological method (Cavalieri principle). RESULTS: The annual decrease (mean +/- SD) of the cerebral volume was 2.1% +/- 1.6% (P < .001). The average volume of the lateral ventricles on the second MRI was increased by 5.6% +/- 3.6% per year (P < .001). The average volume of the cerebellum on the second MRI was decreased by 1.2% +/- 2.2% per year (P < .001). Even though the average cerebral volume was significantly different between men and women on initial MRI and second MRI, the percentage change of the age-related cerebral volume decrease in male and female brains between initial MRI and second MRI were identical. CONCLUSIONS: The findings showed that there was age-related atrophy of cerebrum and cerebellum and age-related disproportional enlargement of lateral ventricles in normal older men and women.",
"title": "Brain volume changes on longitudinal magnetic resonance imaging in normal older people."
},
{
"docid": "MED-1434",
"text": "Silent information regulator two proteins (sirtuins or SIRTs) are a group of histone deacetylases whose activities are dependent on and regulated by nicotinamide adenine dinucleotide (NAD+). They suppress genome-wide transcription, yet upregulate a select set of proteins related to energy metabolism and pro-survival mechanisms, and therefore play a key role in the longevity effects elicited by calorie restriction. Recently, a neuroprotective effect of sirtuins has been reported for both acute and chronic neurological diseases. The focus of this review is to summarize the latest progress regarding the protective effects of sirtuins, with a focus on SIRT1. We first introduce the distribution of sirtuins in the brain and how their expression and activity are regulated. We then highlight their protective effects against common neurological disorders, such as cerebral ischemia, axonal injury, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and multiple sclerosis. Finally, we analyze the mechanisms underlying sirtuin-mediated neuroprotection, centering on their non-histone substrates such as DNA repair enzymes, protein kinases, transcription factors, and coactivators. Collectively, the information compiled here will serve as a comprehensive reference for the actions of sirtuins in the nervous system to date, and will hopefully help to design further experimental research and expand sirtuins as therapeutic targets in the future.",
"title": "Protective effects and mechanisms of sirtuins in the nervous system"
},
{
"docid": "MED-2386",
"text": "OBJECTIVE Emerging in vitro and animal evidence suggests that methylmercury could increase type 2 diabetes, but little evidence exists in humans. We aimed to prospectively determine associations of mercury exposure, as assessed by biomarker measurement, with incident diabetes. RESEARCH DESIGN AND METHODS We used neutron activation analysis to measure toenail mercury, an objective biomarker of methylmercury exposure, in 9,267 adults free of diabetes at baseline in two separate U.S. prospective cohorts. Incident diabetes was identified from biennial questionnaires and confirmed by validated supplementary questionnaire using symptoms, diagnostic tests, and medical therapy. Associations of mercury exposure with incident diabetes were assessed using Cox proportional hazards. RESULTS During mean ± SD follow-up of 19.7 ± 7.0 years, 1,010 new cases of diabetes were diagnosed. The 95th percentile of toenail mercury was 1.32 μg/g in men and 0.76 μg/g in women, corresponding to exposures ∼3.5-fold and 2-fold higher than the U.S. Environmental Protection Agency reference dose. In multivariable analyses, toenail mercury concentrations were not associated with higher incidence of diabetes in women, men, or both cohorts combined. Comparing the highest to lowest quintile of exposure, the hazard ratio (95% CI) for incident diabetes was 0.86 (0.66–1.11) in women, 0.69 (0.42–1.15) in men, and 0.77 (0.61–0.98) in the combined cohorts. Findings were similar when more extreme categories (deciles) of mercury were compared, and in analyses stratified by fish or omega-3 consumption, BMI, and age. CONCLUSIONS These findings from two separate large prospective cohorts do not support adverse effects of methylmercury on development of diabetes in men or women at usual levels of exposure seen in these populations.",
"title": "Methylmercury Exposure and Incident Diabetes in U.S. Men and Women in Two Prospective Cohorts"
},
{
"docid": "MED-4554",
"text": "Modern diets are largely heat-processed and as a result contain high levels of advanced glycation end products (AGEs). Dietary advanced glycation end products (dAGEs) are known to contribute to increased oxidant stress and inflammation, which are linked to the recent epidemics of diabetes and cardiovascular disease. This report significantly expands the available dAGE database, validates the dAGE testing methodology, compares cooking procedures and inhibitory agents on new dAGE formation, and introduces practical approaches for reducing dAGE consumption in daily life. Based on the findings, dry heat promotes new dAGE formation by >10- to 100-fold above the uncooked state across food categories. Animal-derived foods that are high in fat and protein are generally AGE-rich and prone to new AGE formation during cooking. In contrast, carbohydrate-rich foods such as vegetables, fruits, whole grains, and milk contain relatively few AGEs, even after cooking. The formation of new dAGEs during cooking was prevented by the AGE inhibitory compound aminoguanidine and significantly reduced by cooking with moist heat, using shorter cooking times, cooking at lower temperatures, and by use of acidic ingredients such as lemon juice or vinegar. The new dAGE database provides a valuable instrument for estimating dAGE intake and for guiding food choices to reduce dAGE intake.",
"title": "Advanced Glycation End Products in Foods and a Practical Guide to Their Reduction in the Diet"
},
{
"docid": "MED-5236",
"text": "AIMS/HYPOTHESIS: A diet rich in meat has been reported to contribute to the risk of type 2 diabetes. The present study aims to investigate the association between meat consumption and incident type 2 diabetes in the EPIC-InterAct study, a large prospective case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. METHODS: During 11.7 years of follow-up, 12,403 incident cases of type 2 diabetes were identified among 340,234 adults from eight European countries. A centre-stratified random subsample of 16,835 individuals was selected in order to perform a case-cohort design. Prentice-weighted Cox regression analyses were used to estimate HR and 95% CI for incident diabetes according to meat consumption. RESULTS: Overall, multivariate analyses showed significant positive associations with incident type 2 diabetes for increasing consumption of total meat (50 g increments: HR 1.08; 95% CI 1.05, 1.12), red meat (HR 1.08; 95% CI 1.03, 1.13) and processed meat (HR 1.12; 95% CI 1.05, 1.19), and a borderline positive association with meat iron intake. Effect modifications by sex and class of BMI were observed. In men, the results of the overall analyses were confirmed. In women, the association with total and red meat persisted, although attenuated, while an association with poultry consumption also emerged (HR 1.20; 95% CI 1.07, 1.34). These associations were not evident among obese participants. CONCLUSIONS/INTERPRETATION: This prospective study confirms a positive association between high consumption of total and red meat and incident type 2 diabetes in a large cohort of European adults.",
"title": "Association between dietary meat consumption and incident type 2 diabetes: the EPIC-InterAct study."
},
{
"docid": "MED-2114",
"text": "Acne in adolescents of developed countries is an epidemic skin disease and has currently been linked to the Western diet (WD). It is the intention of this viewpoint to discuss the possible impact of WD-mediated nutrient signalling in the pathogenesis of acne. High glycaemic load and dairy protein consumption both increase insulin/insulin-like growth factor-1 (IGF-1) signalling (IIS) that is superimposed on elevated IGF-1 signalling of puberty. The cell's nutritional status is primarily sensed by the forkhead box transcription factor O1 (FoxO1) and the serine/threonine kinase mammalian target of rapamycin complex 1 (mTORC1). Increased IIS extrudes FoxO1 into the cytoplasm, whereas nuclear FoxO1 suppresses hepatic IGF-1 synthesis and thus impairs somatic growth. FoxO1 attenuates androgen signalling, interacts with regulatory proteins important for sebaceous lipogenesis, regulates the activity of innate and adaptive immunity, antagonizes oxidative stress and most importantly functions as a rheostat of mTORC1, the master regulator of cell growth, proliferation and metabolic homoeostasis. Thus, FoxO1 links nutrient availability to mTORC1-driven processes: increased protein and lipid synthesis, cell proliferation, cell differentiation including hyperproliferation of acroinfundibular keratinocytes, sebaceous gland hyperplasia, increased sebaceous lipogenesis, insulin resistance and increased body mass index. Enhanced androgen, TNF-α and IGF-1 signalling due to genetic polymorphisms promoting the risk of acne all converge in mTORC1 activation, which is further enhanced by nutrient signalling of WD. Deeper insights into the molecular interplay of FoxO1/mTORC1-mediated nutrient signalling are thus of critical importance to understand the impact of WD on the promotion of epidemic acne and more serious mTORC1-driven diseases of civilization.",
"title": "Potential role of FoxO1 and mTORC1 in the pathogenesis of Western diet-induced acne"
},
{
"docid": "MED-2116",
"text": "Over the past 10 years, the increase in comprehension of the mechanisms behind acne has been truly exponential. Starting with the ethnological work of Cordain, accelerated by the epidemiological work of Adebamowo, supported by the clinical trials of Smith and Mann, Kwon, DiLandro and others, the interface of diet and acne is coming into focus. Melnik now presents an exceptional pair of papers that illustrate for dermatologists what translational research is all about. The Western diet, the role of dairy, FoxO1 and mTORC1, the interplay of agonists and antagonists, therapeutics present and future – the jigsaw puzzle is coming together.",
"title": "Turning acne on/off via mTORC1"
},
{
"docid": "MED-3316",
"text": "BACKGROUND: Between November, 2006, and May, 2008, a subacute neurological syndrome affected workers from two swine abattoirs in Minnesota and Indiana who had occupational exposure to aerosolised porcine brain. We aimed to describe the pathogenic and immunological characteristics of this illness. METHODS: All patients from two abattoirs who presented or were referred to the Mayo Clinic (Rochester, MN, USA) with neurological symptoms were included. We recorded details of exposure to aerosolised brain tissue and did comprehensive neurological, laboratory, neuroimaging, electrophysiological, pathological, and autoimmune serological assessments. Healthy controls were recruited from the community and from workers at the plant in Minnesota. FINDINGS: 24 patients were identified (21 from Minnesota, three from Indiana). The shortest duration from first exposure to symptom onset was 4 weeks. No infectious agent that could trigger disease was identified. All patients developed polyradiculoneuropathy, which was usually sensory predominant and painful. Two patients had initial CNS manifestations: transverse myelitis and meningoencephalitis. Nerve conduction studies localised abnormalities to the most proximal and distal nerve segments. Quantitative sensory and autonomic testing revealed involvement of large and small sensory fibres and sweat fibres. MRI showed prominent abnormalities of roots and ganglia. Nerve biopsies identified mild demyelination, axonal degeneration, and perivascular inflammation. Protein concentrations were high in the CSF of 18 (86%) of 21 patients. Sera from all patients and 29 (34%) of 85 unaffected workplace controls (but none of 178 community controls) had a distinctive neural-reactive IgG; 75% of patients' sera contained an IgG specific to myelin basic protein. Seropositivity correlated directly with exposure risk in patients and controls. 17 patients required immunomodulatory therapies, six improved spontaneously, and one was lost to follow-up after exposure stopped. INTERPRETATION: The neurological disorder described is autoimmune in origin and is related to occupational exposure to multiple aerosolised porcine brain tissue antigens. The pattern of nerve involvement suggests vulnerability of nerve roots and terminals where the blood-nerve barrier is most permeable. FUNDING: Mayo Clinic Foundation; Minnesota Department of Health; Centers for Disease Control and Prevention. Copyright 2010 Elsevier Ltd. All rights reserved.",
"title": "An outbreak of neurological autoimmunity with polyradiculoneuropathy in workers exposed to aerosolised porcine neural tissue: a descriptive study."
},
{
"docid": "MED-3320",
"text": "OBJECTIVES: Reticuloendotheliosis viruses (REV) are a group of retroviruses like avian leukosis/sarcoma viruses (ALSV) that naturally infect and cause cancers in chickens. We recently found that ALSV antibody levels were associated with job tasks in the poultry industry. The objectives of this study are to examine whether a similar association can be found with REV antibody levels and to examine the correlation between REV and ALSV antibody levels. METHODS: Relative risk was estimated comparing REV antibody levels of 45 poultry workers with those of 44 controls. The expected mean antibody level was predicted for the association with employment by a generalized linear model. Correlation coefficient was measured between ALSV and REV antibody levels. RESULTS: REV antibody levels were significantly higher in poultry workers than in control subjects and were associated with gender and employment conditions, especially employment duration. The relative risk was significantly higher for some job categories. A significant correlation was observed between REV and ALSV antibody levels, which was strong among poultry workers, but weak among the control subjects. CONCLUSION: Antibody levels can be validly used to identify certain job tasks associated with high risk of exposure to REV in the workplace, and the practical implication is recommendations for protection at these job tasks. Importantly, in situations where there is exposure to multiple pathogens in the workplace, the analysis of antibody levels of one pathogen may sufficiently represent exposure to the other correlated pathogens. This suggested exposure assessment may hold true for pathogens with a similar route of transmission.",
"title": "Industrial hygiene assessment of reticuloendotheliosis viruses exposure in the poultry industry."
},
{
"docid": "MED-3436",
"text": "Erectile dysfunction (ED) is an early marker for systemic atherosclerosis and is a predictor for coronary artery disease and cardiac events. The aim of this paper is to convey the importance of addressing cardiovascular risk factors in patients with ED and to inform urologists as well as other physicians who are not specialized in cardiology how to carry out a basic cardiovascular evaluation, including history, physical examination and objective data. We review the evidence and pathophysiology linking ED to cardiovascular disease, and then describe how to carry out a basic cardiovascular evaluation. We present data from the literature showing that appropriate use of lifestyle modifications and medical therapy has a positive effect on mortality, on numerous cardiovascular end points and on ED. Suggestions of when to refer the ED patient to an internist or cardiologist are provided. Identifying and treating cardiovascular risk factors may not only benefit the patient's ED, but it might also save the patient's life.",
"title": "How to save a life during a clinic visit for erectile dysfunction by modifying cardiovascular risk factors."
},
{
"docid": "MED-3312",
"text": "BACKGROUND: Heavy alcohol consumption, viral hepatitis, and diabetes are risk factors for hepatocellular carcinoma (HCC). However, to the authors' knowledge, the information concerning their interaction effect in patients with risk of HCC is sparse. METHODS: A population-based, case-control study of HCC was conducted during 1984-2002. The study involved 295 HCC cases and 435 age-, gender-, and race-matched control subjects among Hispanic and non-Hispanic whites and blacks in Los Angeles County, California. Lifestyle risk factors were ascertained through in-person interviews. Infections with the hepatitis B and C (HCV) viruses were determined using their serologic markers. RESULTS: Fourteen HCC cases but no control subjects tested positive for the hepatitis B surface antigen. Seropositivity for antibodies to HCV was associated with an odds ratio (OR) of 125 (95% confidence interval [95% CI], 17-909) for HCC, whereas seropositivity for antibodies to the hepatitis B core antigen was related to an OR of 2.9 (95% CI, 1.7-5.0). Heavy alcohol consumption and cigarette smoking were found to be independently associated with a statistically significant two to threefold increase in risk of HCC after adjustment for hepatitis B and C serology. Subjects with a history of diabetes had an OR of 2.7 (95% CI, 1.6-4.3) for HCC compared with nondiabetic subjects. A synergistic interaction on HCC risk was observed between heavy alcohol consumption and diabetes (OR = 4.2; 95% CI, 2.6-5.8), heavy alcohol consumption and viral hepatitis (OR = 5.5; 95% CI, 3.9-7.0), or between diabetes and viral hepatitis (OR = 4.8; 95% CI, 2.7-6.9). CONCLUSIONS: Heavy alcohol consumption, diabetes, and viral hepatitis were found to exert independent and synergistic effects on risk of HCC in U.S. blacks and whites. Copyright 2004 American Cancer Society.",
"title": "Synergism of alcohol, diabetes, and viral hepatitis on the risk of hepatocellular carcinoma in blacks and whites in the U.S."
},
{
"docid": "MED-2122",
"text": "OBJECTIVE: To clarify the hormonal context of breast cancer etiology we used data from a large, population-based case-control study to investigate the relationship between breast cancer risk and a history of diabetes mellitus, disorders associated with estrogen stimulation (uterine fibroids, endometriosis, gallstones), and disorders associated with androgen stimulation (acne, hirsutism, and polycystic ovaries). METHODS: Breast cancer patients between 50 and 75 years old were identified from state-wide tumor registries in Wisconsin, Massachusetts, and New Hampshire; controls were randomly selected from drivers' license lists (age less than 65) or Medicare enrollment files (age 65-74). Information on reproductive history, medical history, and personal habits was obtained by telephone interview. A total of 5659 cases and 5928 controls were interviewed and provided suitable data. RESULTS: There was no overall association between breast cancer risk and reported history of diabetes mellitus, endometriosis, uterine fibroids, gallstones, or cholecystectomy. However, the disorders with androgenic associations all conferred an increased risk: the overall odds ratio (OR) for a history of acne was 1.4 (95% CI 1.0-1.9), that for hirsutism was 1.2 (95% CI 0.81-1.8), and that for polycystic ovaries 1.6 (95% CI 0.8-3.2). Diabetes mellitus diagnosed before age 35 conferred an odds ratio of 0.52 (95% 0.25-1.1), while diabetes diagnosed at a later age was associated with an increased risk (OR = 1.2, 95% CI 1.0-1.4). CONCLUSIONS: Androgen-related phenomena are likely to be important in the etiology of breast cancer.",
"title": "Metabolic disorders and breast cancer risk (United States)."
},
{
"docid": "MED-2507",
"text": "Increased plasma levels of adiponectin, metformin therapy of diabetes, rapamycin administration in transplant patients, and lifelong consumption of low-protein plant-based diets have all been linked to decreased risk for various cancers. These benefits may be mediated, at least in part, by down-regulated activity of the mTORC1 complex, a key regulator of protein translation. By boosting the effective availability of the translation initiator eIF4E, mTORC1 activity promotes the translation of a number of \"weak\" mRNAs that code for proteins, often up-regulated in cancer, that promote cellular proliferation, invasiveness, and angiogenesis, and that abet cancer promotion and chemoresistance by opposing apoptosis. Measures which inhibit eIF4E activity, either directly or indirectly, may have utility not only for cancer prevention, but also for the treatment of many cancers in which eIF4E drives malignancy. Since eIF4E is overexpressed in many cancers, strategies which target eIF4E directly--some of which are now being assessed clinically--may have the broadest efficacy in this regard. Many of the \"weak\" mRNAs coding for proteins that promote malignant behavior or chemoresistance are regulated transcriptionally by NF-kappaB and/or Stat3, which are active in a high proportion of cancers; thus, regimens concurrently targeting eIF4E, NF-kappaB, and Stat3 may suppress these proteins at both the transcriptional and translational levels, potentially achieving a very marked reduction in their expression. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "mTORC1 activity as a determinant of cancer risk--rationalizing the cancer-preventive effects of adiponectin, metformin, rapamycin, and low-protein ..."
},
{
"docid": "MED-2509",
"text": "DR (dietary restriction), or reduced food intake without malnutrition, is associated with extended longevity, improved metabolic fitness and increased stress resistance in a wide range of organisms. DR is often referred to as calorie restriction, implying that reduced energy intake is responsible for its widespread and evolutionarily conserved benefits. However, recent data indicate dietary amino acid restriction as a key mediator of DR benefits. In fruitflies, an imbalance in essential amino acid intake is thought to underlie longevity benefits of DR. In mammals, reduced dietary protein or essential amino acid intake can extend longevity, improve metabolic fitness and increase stress resistance. In the present paper we review two evolutionarily conserved signal transduction pathways responsible for sensing amino acid levels. The eIF2α (eukaryotic initiation factor 2α) kinase GCN2 (general amino acid control non-derepressible 2) senses the absence of one or more amino acids by virtue of direct binding to uncharged cognate tRNAs. The presence of certain amino acids, such as leucine, permits activation of the master growth regulating kinase TOR (target of rapamycin). These two signal transduction pathways react to amino acid deprivation by inhibiting general protein translation while at the same time increasing translation of specific mRNAs involved in restoring homoeostasis. Together, these pathways may contribute to the regulation of longevity, metabolic fitness and stress resistance.",
"title": "Amino acid sensing in dietary-restriction-mediated longevity: roles of signal-transducing kinases GCN2 and TOR"
},
{
"docid": "MED-1797",
"text": "The selection of meat-type chickens (broilers) for rapid growth has been accompanied by excessive fat deposition. In this study, we analysed 53 candidate genes that are associated with obesity and obesity-related traits in humans, for which we found chicken orthologues by BLAST searches. We have identified single nucleotide polymorphisms (SNPs) with significant differences in allele frequencies between broilers and layers in each of the following six candidate genes: adrenergic, beta-2-, receptor, surface (ADRB2); melanocortin 5 receptor (MC5R); leptin receptor (LEPR), McKusick-Kaufman syndrome (MKKS), milk fat globule-EGF factor 8 protein (MFGE8) and adenylate kinase 1 (AK1). To examine associations with fatness and/or body weight, we used birds of extreme phenotypes in F(2) and backcross populations with varying levels of abdominal fat weight per cent (%AFW) and body weight. We then assessed the level of gene expression by real-time PCR. In two genes, ADRB2 and MFGE8, we found significant association with %AFW. The ADRB2 gene was found to have a significantly higher expression in the liver of lean chickens compared with those of the fat individuals. We believe that this approach can be applied for the identification of other quantitative genes. © 2011 The Authors, Animal Genetics © 2011 Stichting International Foundation for Animal Genetics.",
"title": "Comparative genome analysis with the human genome reveals chicken genes associated with fatness and body weight."
}
] |
[
{
"docid": "MED-5229",
"text": "Disease risk factors identified in epidemiological studies serve as important public health tools, helping clinicians identify individuals who may benefit from more aggressive screening or risk-modification procedures, allowing policymakers to prioritize intervention programs, and encouraging at-risk individuals to modify behavior and improve their health. These factors have been based primarily on evidence from cross-sectional and prospective studies, as most do not lend themselves to randomized trials. While some risk factors are not modifiable, eating habits are subject to change through both individual action and broader policy initiatives. Meat consumption has been frequently investigated as a variable associated with diabetes risk, but it has not yet been described as a diabetes risk factor. In this article, we evaluate the evidence supporting the use of meat consumption as a clinically useful risk factor for type 2 diabetes, based on studies evaluating the risks associated with meat consumption as a categorical dietary characteristic (i.e., meat consumption versus no meat consumption), as a scalar variable (i.e., gradations of meat consumption), or as part of a broader dietary pattern.",
"title": "Meat Consumption as a Risk Factor for Type 2 Diabetes"
},
{
"docid": "MED-4758",
"text": "AIM: To examine the relation between meat intake and diabetes occurrence in adults. METHODS: In a prospective cohort study we examined the relation between diet and incident diabetes recorded among 8,401 cohort members (ages 45-88 years) of the Adventist Mortality Study and Adventist Health Study (California, USA) who were non-diabetic at baseline. During the 17-year follow-up, we identified 543 incident diabetes cases. RESULTS: (1) Subjects who were weekly consumers of all meats were 29% (OR = 1.29; 95% CI 1.08, 1.55) more likely (relative to zero meat intake) to develop diabetes. (2) Subjects who consumed any processed meats (salted fish and frankfurters) were 38% (OR = 1.38; 95% CI 1.05-1.82) more likely to develop diabetes. (3) Long-term adherence (over a 17-year interval) to a diet that included at least weekly meat intake was associated with a 74% increase (OR = 1.74; 95% CI 1.36-2.22) in odds of diabetes relative to long-term adherence to a vegetarian diet (zero meat intake). Further analyses indicated that some of this risk may be attributable to obesity and/or weight gain--both of which were strong risk factors in this cohort. It is noteworthy that even after control for weight and weight change, weekly meat intake remained an important risk factor (OR = 1.38; 95% CI 1.06-1.68) for diabetes [corrected]. CONCLUSIONS: Our findings raise the possibility that meat intake, particularly processed meats, is a dietary risk factor for diabetes. 2008 S. Karger AG, Basel.",
"title": "Meats, processed meats, obesity, weight gain and occurrence of diabetes among adults: findings from Adventist Health Studies."
},
{
"docid": "MED-1541",
"text": "We propose the hypothesis that a vegetarian diet reduces the risk of developing diabetes. Findings that have generated this hypothesis are from a population of 25,698 adult White Seventh-day Adventists identified in 1960. During 21 years of follow-up, the risk of diabetes as an underlying cause of death in Adventists was approximately one-half the risk for all US Whites. Within the male Adventist population, vegetarians had a substantially lower risk than non-vegetarians of diabetes as an underlying or contributing cause of death. Within both the male and female Adventist populations, the prevalence of self-reported diabetes also was lower in vegetarians than in non-vegetarians. The associations observed between diabetes and meat consumption were apparently not due to confounding by over- or under-weight, other selected dietary factors, or physical activity. All of the associations between meat consumption and diabetes were stronger in males than in females.",
"title": "Does a vegetarian diet reduce the occurrence of diabetes?"
},
{
"docid": "MED-2852",
"text": "AIMS/HYPOTHESIS: The aim of this study was to prospectively examine whether dietary patterns are related to risk of gestational diabetes mellitus (GDM). METHODS: This prospective cohort study included 13,110 women who were free of cardiovascular disease, cancer, type 2 diabetes and history of GDM. Subjects completed a validated semi-quantitative food frequency questionnaire in 1991, and reported at least one singleton pregnancy between 1992 and 1998 in the Nurses' Health Study II. Two major dietary patterns (i.e. 'prudent' and 'Western') were identified through factor analysis. The prudent pattern was characterised by a high intake of fruit, green leafy vegetables, poultry and fish, whereas the Western pattern was characterised by high intake of red meat, processed meat, refined grain products, sweets, French fries and pizza. RESULTS: We documented 758 incident cases of GDM. After adjustment for age, parity, pre-pregnancy BMI and other covariates, the relative risk (RR) of GDM, comparing the highest with the lowest quintile of the Western pattern scores, was 1.63 (95% CI 1.20-2.21; p (trend)=0.001), whereas the RR comparing the lowest with the highest quintile of the prudent pattern scores was 1.39 (95% CI 1.08-1.80; p (trend)=0.018). The RR for each increment of one serving/day was 1.61 (95% CI 1.25-2.07) for red meat and 1.64 (95% CI 1.13-2.38) for processed meat. CONCLUSIONS/INTERPRETATION: These findings suggest that pre-pregnancy dietary patterns may affect women's risk of developing GDM. A diet high in red and processed meat was associated with a significantly elevated risk.",
"title": "A prospective study of dietary patterns, meat intake and the risk of gestational diabetes mellitus."
},
{
"docid": "MED-4493",
"text": "Processed meat intake may be involved in the etiology of colorectal cancer, a major cause of death in affluent countries. The epidemiologic studies published to date conclude that the excess risk in the highest category of processed meat-eaters is comprised between 20 and 50% compared with non-eaters. In addition, the excess risk per gram of intake is clearly higher than that of fresh red meat. Several hypotheses, which are mainly based on studies carried out on red meat, may explain why processed meat intake is linked to cancer risk. Those that have been tested experimentally are (i) that high-fat diets could promote carcinogenesis via insulin resistance or fecal bile acids; (ii) that cooking meat at a high temperature forms carcinogenic heterocyclic amines and polycyclic aromatic hydrocarbons; (iii) that carcinogenic N-nitroso compounds are formed in meat and endogenously; (iv) that heme iron in red meat can promote carcinogenesis because it increases cell proliferation in the mucosa, through lipoperoxidation and/or cytotoxicity of fecal water. Nitrosation might increase the toxicity of heme in cured products. Solving this puzzle is a challenge that would permit to reduce cancer load by changing the processes rather than by banning processed meat.",
"title": "Processed meat and colorectal cancer: a review of epidemiologic and experimental evidence"
},
{
"docid": "MED-5344",
"text": "AIMS: Coronary heart disease (CHD) is a leading cause of death among men and women globally. Women develop CHD about 10 years later than men, yet the reasons for this are unclear. The purpose of this report is to determine if differences in risk factor distributions exist between women and men across various age categories to help explain why women develop acute MI later than men. METHODS AND RESULTS: We used the INTERHEART global case-control study including 27 098 participants from 52 countries, 6787 of whom were women. The median age of first acute MI was higher in women than men (65 vs. 56 years; P < 0.0001). Nine modifiable risk factors were associated with MI in women and men. Hypertension [2.95(2.66 -3.28) vs. 2.32(2.16-2.48)], diabetes [4.26(3.68-4.94) vs. 2.67(2.43-2.94), physical activity [0.48(0.41-0.57) vs. 0.77(0.71-0.83)], and moderate alcohol use [0.41(0.34-0.50) vs. 0.88(0.82-0.94)] were more strongly associated with MI among women than men. The association of abnormal lipids, current smoking, abdominal obesity, high risk diet, and psychosocial stress factors with MI was similar in women and men. Risk factors associations were generally stronger among younger individuals compared to older women and men. The population attributable risk (PAR) of all nine risk factors exceeded 94%, and was similar among women and men (96 vs. 93%). Men were significantly more likely to suffer a MI prior to 60 years of age than were women, however, after adjusting for levels of risk factors, the sex difference in the probability of MI cases occurring before the age of 60 years was reduced by more than 80%. CONCLUSION: Women experience their first acute MI on average 9 years later than men. Nine modifiable risk factors are significantly associated with acute MI in both men and women and explain greater than 90% of the PAR. The difference in age of first MI is largely explained by the higher risk factor levels at younger ages in men compared to women.",
"title": "Risk factors for myocardial infarction in women and men: insights from the INTERHEART study."
},
{
"docid": "MED-2154",
"text": "Obesity has been recognized as a key component of the metabolic syndrome, a cluster of risk factors associated with diabetes and cardiovascular morbidity. In addition, obesity has been linked to higher frequency of cancers in a variety of tissues including the liver. Liver cancer most often occurs as hepatocellular carcinoma (HCC) complicating cirrhosis due to chronic viral infection or toxic injury and remains the third leading cause of cancer death in the world. However, HCC is increasingly diagnosed among individuals with obesity and related disorders. As these metabolic conditions have become globally prevalent, they coexist with well-established risk factors of HCC and create a unique challenge for the liver as a chronically diseased organ. Obesity-associated HCC has recently been attributed to molecular mechanisms such as chronic inflammation due to adipose tissue remodeling and pro-inflammatory adipokine secretion, ectopic lipid accumulation and lipotoxicity, altered gut microbiota, and disrupted senescence in stellate cells, as well as insulin resistance leading to increased levels of insulin and insulin-like growth factors. These mechanisms synergize with those occurring in chronic liver disease resulting from other etiologies and accelerate the development of HCC before or after the onset of cirrhosis. Increasingly common interactions between oncogenic pathways linked to obesity and chronic liver disease may explain why HCC is one of the few malignancies with rising incidence in developed countries. Better understanding of this complex process will improve our strategies of cancer prevention, prediction, and surveillance. Published by Elsevier Inc.",
"title": "Obesity-associated mechanisms of hepatocarcinogenesis."
},
{
"docid": "MED-4494",
"text": "Background: Fifty percent of American Indians (AIs) develop diabetes by age 55 y. Whether processed meat is associated with the risk of diabetes in AIs, a rural population with a high intake of processed meat (eg, canned meats in general, referred to as “spam”) and a high rate of diabetes, is unknown. Objective: We examined the associations of usual intake of processed meat with incident diabetes in AIs. Design: This prospective cohort study included AI participants from the Strong Heart Family Study who were free of diabetes and cardiovascular disease at baseline and who participated in a 5-y follow-up examination (n = 2001). Dietary intake was ascertained by using a Block food-frequency questionnaire at baseline. Incident diabetes was defined on the basis of 2003 American Diabetes Association criteria. Generalized estimating equations were used to examine the associations of dietary intake with incident diabetes. Results: We identified 243 incident cases of diabetes. In a comparison of upper and lower quartiles, intake of processed meat was associated with a higher risk of incident diabetes (OR: 1.63; 95% CI: 1.21, 2.63), after adjustment for potential confounders. The relation was particularly strong for spam (OR for the comparison of upper and lower quartiles: 2.06; 95% CI: 1.30, 3.27). Intake of unprocessed red meat was not associated with incident diabetes (OR for the comparison of upper and lower quartiles: 0.90; 95% CI: 0.59, 1.37). Conclusion: The consumption of processed meat, such as spam, but not unprocessed red meat, was associated with higher risk of diabetes in AIs, a rural population at high risk of diabetes and with limited access to healthy foods.",
"title": "Associations of processed meat and unprocessed red meat intake with incident diabetes: the Strong Heart Family Study"
},
{
"docid": "MED-5299",
"text": "Background Knowledge of the number of deaths caused by risk factors is needed for health policy and priority setting. Our aim was to estimate the mortality effects of the following 12 modifiable dietary, lifestyle, and metabolic risk factors in the United States (US) using consistent and comparable methods: high blood glucose, low-density lipoprotein (LDL) cholesterol, and blood pressure; overweight–obesity; high dietary trans fatty acids and salt; low dietary polyunsaturated fatty acids, omega-3 fatty acids (seafood), and fruits and vegetables; physical inactivity; alcohol use; and tobacco smoking. Methods and Findings We used data on risk factor exposures in the US population from nationally representative health surveys and disease-specific mortality statistics from the National Center for Health Statistics. We obtained the etiological effects of risk factors on disease-specific mortality, by age, from systematic reviews and meta-analyses of epidemiological studies that had adjusted (i) for major potential confounders, and (ii) where possible for regression dilution bias. We estimated the number of disease-specific deaths attributable to all non-optimal levels of each risk factor exposure, by age and sex. In 2005, tobacco smoking and high blood pressure were responsible for an estimated 467,000 (95% confidence interval [CI] 436,000–500,000) and 395,000 (372,000–414,000) deaths, accounting for about one in five or six deaths in US adults. Overweight–obesity (216,000; 188,000–237,000) and physical inactivity (191,000; 164,000–222,000) were each responsible for nearly 1 in 10 deaths. High dietary salt (102,000; 97,000–107,000), low dietary omega-3 fatty acids (84,000; 72,000–96,000), and high dietary trans fatty acids (82,000; 63,000–97,000) were the dietary risks with the largest mortality effects. Although 26,000 (23,000–40,000) deaths from ischemic heart disease, ischemic stroke, and diabetes were averted by current alcohol use, they were outweighed by 90,000 (88,000–94,000) deaths from other cardiovascular diseases, cancers, liver cirrhosis, pancreatitis, alcohol use disorders, road traffic and other injuries, and violence. Conclusions Smoking and high blood pressure, which both have effective interventions, are responsible for the largest number of deaths in the US. Other dietary, lifestyle, and metabolic risk factors for chronic diseases also cause a substantial number of deaths in the US. Please see later in the article for Editors' Summary Editors' Summary A number of modifiable factors are responsible for many premature or preventable deaths. For example, being overweight or obese shortens life expectancy, while half of all long-term tobacco smokers in Western populations will die prematurely from a disease directly related to smoking. Modifiable risk factors fall into three main groups. First, there are lifestyle risk factors. These include tobacco smoking, physical inactivity, and excessive alcohol use (small amounts of alcohol may actually prevent diabetes and some types of heart disease and stroke). Second, there are dietary risk factors such as a high salt intake and a low intake of fruits and vegetables. Finally, there are “metabolic risk factors,” which shorten life expectancy by increasing a person's chances of developing cardiovascular disease (in particular, heart problems and strokes) and diabetes. Metabolic risk factors include having high blood pressure or blood cholesterol and being overweight or obese. Why Was This Study Done? It should be possible to reduce preventable deaths by changing modifiable risk factors through introducing public health policies, programs and regulations that reduce exposures to these risk factors. However, it is important to know how many deaths are caused by each risk factor before developing policies and programs that aim to improve a nation's health. Although previous studies have provided some information on the numbers of premature deaths caused by modifiable risk factors, there are two problems with these studies. First, they have not used consistent and comparable methods to estimate the number of deaths attributable to different risk factors. Second, they have rarely considered the effects of dietary and metabolic risk factors. In this new study, the researchers estimate the number of deaths due to 12 different modifiable dietary, lifestyle, and metabolic risk factors for the United States population. They use a method called “comparative risk assessment.” This approach estimates the number of deaths that would be prevented if current distributions of risk factor exposures were changed to hypothetical optimal distributions. What Did the Researchers Do and Find? The researchers extracted data on exposures to these 12 selected risk factors from US national health surveys, and they obtained information on deaths from difference diseases for 2005 from the US National Center for Health Statistics. They used previously published studies to estimate how much each risk factor increases the risk of death from each disease. The researchers then used a mathematical formula to estimate the numbers of deaths caused by each risk factor. Of the 2.5 million US deaths in 2005, they estimate that nearly half a million were associated with tobacco smoking and about 400,000 were associated with high blood pressure. These two risk factors therefore each accounted for about 1 in 5 deaths in US adults. Overweight–obesity and physical inactivity were each responsible for nearly 1 in 10 deaths. Among the dietary factors examined, high dietary salt intake had the largest effect, being responsible for 4% of deaths in adults. Finally, while alcohol use prevented 26,000 deaths from ischemic heart disease, ischemic stroke, and diabetes, the researchers estimate that it caused 90,000 deaths from other types of cardiovascular diseases, other medical conditions, and road traffic accidents and violence. What Do These Findings Mean? These findings indicate that smoking and high blood pressure are responsible for the largest number of preventable deaths in the US, but that several other modifiable risk factors also cause many deaths. Although the accuracy of some of the estimates obtained in this study will be affected by the quality of the data used, these findings suggest that targeting a handful of risk factors could greatly reduce premature mortality in the US. The findings might also apply to other countries, although the risk factors responsible for most preventable deaths may vary between countries. Importantly, effective individual-level and population-wide interventions are already available to reduce people's exposure to the two risk factors responsible for most preventable deaths in the US. The researchers also suggest that combinations of regulation, pricing, and education have the potential to reduce the exposure of US residents to other risk factors that are likely to shorten their lives. Additional Information Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000058.",
"title": "The Preventable Causes of Death in the United States: Comparative Risk Assessment of Dietary, Lifestyle, and Metabolic Risk Factors"
},
{
"docid": "MED-2305",
"text": "BACKGROUND: Our objective was to describe the reduction in relative risk of developing major chronic diseases such as cardiovascular disease, diabetes, and cancer associated with 4 healthy lifestyle factors among German adults. METHODS: We used data from 23,153 German participants aged 35 to 65 years from the European Prospective Investigation Into Cancer and Nutrition-Potsdam study. End points included confirmed incident type 2 diabetes mellitus, myocardial infarction, stroke, and cancer. The 4 factors were never smoking, having a body mass index lower than 30 (calculated as weight in kilograms divided by height in meters squared), performing 3.5 h/wk or more of physical activity, and adhering to healthy dietary principles (high intake of fruits, vegetables, and whole-grain bread and low meat consumption). The 4 factors (healthy, 1 point; unhealthy, 0 points) were summed to form an index that ranged from 0 to 4. RESULTS: During a mean follow-up of 7.8 years, 2006 participants developed new-onset diabetes (3.7%), myocardial infarction (0.9%), stroke (0.8%), or cancer (3.8%). Fewer than 4% of participants had zero healthy factors, most had 1 to 3 healthy factors, and approximately 9% had 4 factors. After adjusting for age, sex, educational status, and occupational status, the hazard ratio for developing a chronic disease decreased progressively as the number of healthy factors increased. Participants with all 4 factors at baseline had a 78% (95% confidence interval [CI], 72% to 83%) lower risk of developing a chronic disease (diabetes, 93% [95% CI, 88% to 95%]; myocardial infarction, 81% [95% CI, 47% to 93%]; stroke, 50% [95% CI, -18% to 79%]; and cancer, 36% [95% CI, 5% to 57%]) than participants without a healthy factor. CONCLUSION: Adhering to 4 simple healthy lifestyle factors can have a strong impact on the prevention of chronic diseases.",
"title": "Healthy living is the best revenge: findings from the European Prospective Investigation Into Cancer and Nutrition-Potsdam study."
},
{
"docid": "MED-1672",
"text": "The intake of added sugars, such as from table sugar (sucrose) and high-fructose corn syrup has increased dramatically in the last hundred years and correlates closely with the rise in obesity, metabolic syndrome, and diabetes. Fructose is a major component of added sugars and is distinct from other sugars in its ability to cause intracellular ATP depletion, nucleotide turnover, and the generation of uric acid. In this article, we revisit the hypothesis that it is this unique aspect of fructose metabolism that accounts for why fructose intake increases the risk for metabolic syndrome. Recent studies show that fructose-induced uric acid generation causes mitochondrial oxidative stress that stimulates fat accumulation independent of excessive caloric intake. These studies challenge the long-standing dogma that “a calorie is just a calorie” and suggest that the metabolic effects of food may matter as much as its energy content. The discovery that fructose-mediated generation of uric acid may have a causal role in diabetes and obesity provides new insights into pathogenesis and therapies for this important disease.",
"title": "Sugar, Uric Acid, and the Etiology of Diabetes and Obesity"
},
{
"docid": "MED-2153",
"text": "Background: Increasing nut intake has been associated with reduced risk of diabetes mellitus, which is a risk factor for pancreatic cancer. Methods: We prospectively followed 75 680 women in the Nurses' Health Study, and examined the association between nut consumption and pancreatic cancer risk. Participants with a previous history of cancer were excluded. Nut consumption was assessed at baseline and updated every 2 to 4 years. Relative risks (RRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards models. Results: We documented 466 incident cases of pancreatic cancer. After adjusting for age, height, smoking, physical activity, and total energy intake, women who consumed a 28-g (1 oz) serving size of nuts ⩾2 times per week experienced a significantly lower risk of pancreatic cancer (RR, 0.65; 95% CI, 0.47–0.92; P for trend=0.007) when compared with those who largely abstained from nuts. The results did not appreciably change after further adjustment for body mass index (BMI) and history of diabetes mellitus (RR, 0.68; 95% CI, 0.48–0.95; P for trend=0.01). The inverse association persisted within strata defined by BMI, physical activity, smoking, and intakes of red meat, fruits, and vegetables. Conclusion: Frequent nut consumption is inversely associated with risk of pancreatic cancer in this large prospective cohort of women, independent of other potential risk factors for pancreatic cancer.",
"title": "Nut consumption and risk of pancreatic cancer in women"
},
{
"docid": "MED-1305",
"text": "This viewpoint aims to 1) review the available scientific literature on the relationship between whole grain consumption and body weight regulation; 2) evaluate the potential mechanisms whereby whole grain intake may help reduce overweight and 3) try to understand why epidemiological studies and clinical trials provide diverging results on this topic. All the prospective epidemiological studies demonstrate that a higher intake of whole grains is associated with lower BMI and body weight gain. However, these results do not clarify whether whole grain consumption is simply a marker of a healthier lifestyle or a factor favoring \"per se\" lower body weight. Habitual whole grain consumption seems to cause lower body weight by multiple mechanisms such as lower energy density of whole grain based products, lower glycemic index, fermentation of non digestible carbohydrates (satiety signals) and finally by modulating intestinal microflora. In contrast with epidemiological evidence, the results of few clinical trials do not confirm that a whole grain low-calorie diet is more effective in reducing body weight than a refined cereal diet, but their results may have been affected by small sample size or short duration of the intervention. Therefore, further intervention studies with adequate methodology are needed to clarify this question. For the time being, whole grain consumption can be recommended as one of the features of the diet that may help control body weight but also because is associated with a lower risk to develop type 2 diabetes, cardiovascular diseases and cancer. Copyright © 2011 Elsevier B.V. All rights reserved.",
"title": "Whole grain intake in relation to body weight: from epidemiological evidence to clinical trials."
},
{
"docid": "MED-4230",
"text": "PURPOSE OF REVIEW: Although age, genetics, and sex steroid hormones play prominent roles in the cause of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS), recent epidemiological studies suggest that modifiable lifestyle factors also contribute substantially to the pathogenesis of these conditions. RECENT FINDINGS: Lifestyle and metabolic factors associated with significantly increased risks of benign prostatic hyperplasia and lower urinary tract symptoms include obesity, diabetes, and meat and fat consumption. Factors associated with decreased risks include physical activity, moderate alcohol intake, and vegetable consumption. Factors for which no clear risk patterns have emerged include lipids and smoking. Randomized clinical trials of lifestyle alterations - such as weight loss, exercise, and diet - for the prevention or treatment of benign prostatic hyperplasia and lower urinary tract symptoms have yet to be performed. SUMMARY: Lifestyle factors present a novel opportunity for the prevention and treatment of benign prostatic hyperplasia and lower urinary tract symptoms. Although clinical trials of lifestyle modifications have not yet been undertaken, promotion of healthy lifestyle alternatives within the context of standard benign prostatic hyperplasia and lower urinary tract symptoms treatment algorithms is potentially beneficial.",
"title": "Lifestyle factors, benign prostatic hyperplasia, and lower urinary tract symptoms."
},
{
"docid": "MED-2978",
"text": "Diets high in protein have shown positive effects on short-term weight reduction and glycaemic control. However, the understanding of how dietary macronutrient composition relates to long-term risk of type 2 diabetes is limited. The aim of the present study was to examine intakes of macronutrients, fibre and protein sources in relation to incident type 2 diabetes. In total, 27 140 individuals, aged 45-74 years, from the population-based Malmö Diet and Cancer cohort, were included. Dietary data were collected with a modified diet history method, including registration of cooked meals. During 12 years of follow-up, 1709 incident type 2 diabetes cases were identified. High protein intake was associated with increased risk of type 2 diabetes (hazard ratio (HR) 1.27 for highest compared with lowest quintile; 95 % CI 1.08, 1.49; P for trend = 0.01). When protein consumption increased by 5 % of energy at the expense of carbohydrates (HR 1.20; 95 % CI 1.09, 1.33) or fat (HR 1.21; 95 % CI 1.09, 1.33), increased diabetes risk was observed. Intakes in the highest quintiles of processed meat (HR 1.16; 95 % CI 1.00, 1.36; P for trend = 0.01) and eggs (HR 1.21; 95 % CI 1.04, 1.41; P for trend = 0.02) were associated with increased risk. Intake of fibre-rich bread and cereals was inversely associated with type 2 diabetes (HR 0.84; 95 % CI 0.73, 0.98; P for trend = 0.004). In conclusion, results from the present large population-based prospective study indicate that high protein intake is associated with increased risk of type 2 diabetes. Replacing protein with carbohydrates may be favourable, especially if fibre-rich breads and cereals are chosen as carbohydrate sources.",
"title": "High intakes of protein and processed meat associate with increased incidence of type 2 diabetes."
},
{
"docid": "MED-1055",
"text": "OBJECTIVE: To indicate why the world's most powerful nation state and one powerful sector of the food and drink production and manufacturing industry are determined to demolish the 2004 WHO (World Health Organization) global strategy on diet, physical activity and health, and to disassociate it from the 2003 WHO/FAO (Food and Agriculture Organization) expert report on diet, nutrition and the prevention of chronic diseases, which with its background papers is the immediate scientific basis for the strategy. To encourage representatives of nation states at the 2004 WHO World Health Assembly to support the strategy together with the report, so that the strategy is explicit and quantified, and responds to the need expressed by member states at the 2002 World Health Assembly. This is for an effective global strategy to prevent and control chronic diseases whose prevalence is increased by nutrient-poor food low in vegetables and fruits and high in energy-dense fatty, sugary and/or salty foods and drinks and also by physical inactivity. Of these diseases, obesity, diabetes, cardiovascular diseases and cancers of several sites are now the chief causes of morbidity and mortality in most countries in the world. METHOD: A summary of the global strategy and its roots in scientific knowledge accumulated over the last half-century. Reasons why the global strategy and the expert report are opposed by the current US government and the world sugar industry, with some reference to modern historical context. A summary of the trajectory of the global strategy since its first draft made in early 2003, and a further summary of its weaknesses, strengths and potential. CONCLUSION: The 2004 WHO global strategy and the 2003 WHO/FAO expert report are perceived by the current US administration as an impediment to US trade and international policy, within a general context of current US government hostility to the UN (United Nations) system as a brake on the exercise of its power as the world's dominant nation. Policy-makers throughout the world should be aware of the contexts of current pressures put on them by powerful nation states and sectors of industry whose ideologies and commercial interests are challenged by international initiatives designed to improve public health and to leave a better legacy for future generations.",
"title": "Why the Bush administration and the global sugar industry are determined to demolish the 2004 WHO global strategy on diet, physical activity and he..."
},
{
"docid": "MED-5232",
"text": "Insulin resistance is a cardinal feature of type 2 diabetes and is characteristic of a wide range of other clinical and experimental settings. Little is known about why insulin resistance occurs in so many contexts. Do the various insults that trigger insulin resistance act through a common mechanism? Or, as has been suggested, do they use distinct cellular pathways? Here we report a genomic analysis of two cellular models of insulin resistance, one induced by treatment with the cytokine tumour-necrosis factor-alpha and the other with the glucocorticoid dexamethasone. Gene expression analysis suggests that reactive oxygen species (ROS) levels are increased in both models, and we confirmed this through measures of cellular redox state. ROS have previously been proposed to be involved in insulin resistance, although evidence for a causal role has been scant. We tested this hypothesis in cell culture using six treatments designed to alter ROS levels, including two small molecules and four transgenes; all ameliorated insulin resistance to varying degrees. One of these treatments was tested in obese, insulin-resistant mice and was shown to improve insulin sensitivity and glucose homeostasis. Together, our findings suggest that increased ROS levels are an important trigger for insulin resistance in numerous settings.",
"title": "Reactive oxygen species have a causal role in multiple forms of insulin resistance."
},
{
"docid": "MED-1812",
"text": "Epidemiologic studies of diet and pancreas cancer are few, and include ecologic comparisons and a limited number of prospective and case-control studies. Foods and/or nutrients that have been suggested to be associated with increased risk of this cancer include total fat intake, eggs, animal protein, sugar, meat, coffee and butter. Consumption of raw fruits and vegetables has been consistently associated with decreased risk. Dietary habits and medical history variables were evaluated in a prospective study of fatal pancreas cancer among 34,000 California Seventh-day Adventists between 1976 and 1983. Forty deaths from pancreas cancer occurred during the follow-up period. Compared to all US whites, Adventists experienced decreased risk from pancreas cancer death (standardized mortality ratio [SMR] = 72 for men; 90 for women), which was not statistically significant. Although there was a suggestive relationship between increasing meat, egg, and coffee consumption and increased pancreatic cancer risk, these variables were not significantly related to risk after controlling for cigarette smoking. However, increasing consumption of vegetarian protein products, beans, lentils, and peas as well as dried fruit was associated with highly significant protective relationships to pancreas cancer risk. A prior history of diabetes was associated with increased risk of subsequent fatal pancreas cancer, as was a history of surgery for peptic or duodenal ulcer. A history of tonsillectomy was associated with a slight, nonsignificant protective relationship as was history of various allergic reactions. These findings suggest that the protective relationships associated with frequent consumption of vegetables and fruits high in protease-inhibitor content are more important than any increase in pancreas cancer risk attendant on frequent consumption of meat or other animal products. Furthermore, the previously reported positive associations between diabetes and abdominal surgery and pancreas cancer risk are supported in these data.",
"title": "Dietary habits and past medical history as related to fatal pancreas cancer risk among Adventists."
},
{
"docid": "MED-5198",
"text": "The incidence of colorectal cancer (CRC) is dramatically higher in African Americans (AAs) than in Native Africans (NAs) (60:100,000 vs. <1:100,000) and slightly higher than in Caucasian Americans (CAs). To explore whether the difference could be explained by interactions between diet and colonic bacterial flora, we compared randomly selected samples of healthy 50- to 65-y-old AAs (n = 17) with NAs (n = 18) and CAs (n = 17). Diet was measured by 3-d recall, and colonic metabolism by breath hydrogen and methane responses to oral lactulose. Fecal samples were cultured for 7-alpha dehydroxylating bacteria and Lactobacillus plantarum. Colonoscopic mucosal biopsies were taken to measure proliferation rates. In comparison with NAs, AAs consumed more (P < 0.01) protein (94 +/- 9.3 vs. 58 +/- 4.1 g/d) and fat (114 +/- 11.2 vs. 38 +/- 3.0 g/d), meat, saturated fat, and cholesterol. However, they also consumed more (P < 0.05) calcium, vitamin A, and vitamin C, and fiber intake was the same. Breath hydrogen was higher (P < 0.0001) and methane lower in AAs, and fecal colony counts of 7-alpha dehydroxylating bacteria were higher and of Lactobacilli were lower. Colonic crypt cell proliferation rates were dramatically higher in AAs (21.8 +/- 1.1% vs. 3.2 +/- 0.8% labeling, P < 0.0001). In conclusion, the higher CRC risk and mucosal proliferation rates in AAs than in NAs were associated with higher dietary intakes of animal products and higher colonic populations of potentially toxic hydrogen and secondary bile-salt-producing bacteria. This supports our hypothesis that CRC risk is determined by interactions between the external (dietary) and internal (bacterial) environments.",
"title": "Why do African Americans get more colon cancer than Native Africans?"
},
{
"docid": "MED-4825",
"text": "Pancreatic cancer kills more than 250,000 people each year worldwide and has a poor prognosis. The aim of this article is to critically review the epidemiologic evidence for exposures that may either increase or decrease the risk. A Medline search was performed for epidemiologic studies and reviews published up to April 2007. Consistent evidence of a positive association was found for family history and cigarette smoking. Many studies documented a positive association with diabetes mellitus and chronic pancreatitis, although the etiologic mechanisms are unclear. Other associations were detected, but the results were either inconsistent or from few studies. These included positive associations with red meat, sugar, fat, body mass index, gallstones, and Helicobacter pylori, and protective effects of increasing parity, dietary folate, aspirin, and statins. There was no evidence linking alcohol or coffee consumption with an increased risk of pancreatic cancer. The associations with many exposures need to be clarified from further epidemiologic work in which there is both precise measurement of risk factors, adjustment for potential confounders, and, for dietary studies, information recorded on the method of food preparation and pattern of consumption. Such work is important to reduce the incidence of this fatal disease.",
"title": "Pancreatic cancer: a review of the evidence on causation."
},
{
"docid": "MED-2584",
"text": "In a 6-year prospective study, the authors examined the relation between diet and incident colon cancer among 32,051 non-Hispanic white cohort members of the Adventist Health Study (California, 1976-1982) who, at baseline, had no documented or reported history of cancer. The risk of colon cancer was determined from proportional hazards regression with adjustment for age and other covariates. The authors found a positive association with total meat intake (risk ratio (RR) for > or =1 time/week vs. no meat intake = 1.85, 95% confidence interval (CI) 1.19-2.87; p for trend = 0.01) and, among subjects who favored specific types of meat, positive associations with red meat intake (RR for > or =1 time/week vs. no red meat intake = 1.90, 95% CI 1.16-3.11; p for trend = 0.02) and white meat intake (RR for > or =1 time/week vs. no white meat intake = 3.29, 95% CI 1.60-6.75; p for trend = 0.006). An inverse association with legume intake (RR for >2 times/week vs. <1 time/week = 0.53, 95% CI 0.33-0.86; p for trend = 0.03) was observed. Among men, a positive association with body mass index was observed (relative to the RR for tertile III (>25.6 kg/m2) vs. tertile I (<22.5 kg/m2) = 2.63, 95% CI 1.12-6.13; p for trend = 0.05). A complex relation was identified whereby subjects exhibiting a high red meat intake, a low legume intake, and a high body mass experienced a more than threefold elevation in risk relative to all other patterns based on these variables. This pattern of putative risk factors would likely contribute to increases in both insulin resistance (high body mass, high red meat intake) and glycemic load (low legume intake), a synergism that, if causal, implicates hyperinsulinemic exposure in colon carcinogenesis. The overall findings from this cohort identify both red meat intake and white meat intake as important dietary risk factors for colon cancer and raise the possibility that the risk due to red meat intake reflects a more complex etiology.",
"title": "Dietary risk factors for colon cancer in a low-risk population."
},
{
"docid": "MED-3770",
"text": "Background: Comparisons of the cost of different foods relative to their energy and nutritive value were conducted in the 1800s by the US Department of Agriculture (USDA). Objective: The objective was to reestablish the relations between food cost, energy, and nutrients by using contemporary nutrient composition and food prices data from the USDA. Design: The USDA Food and Nutrient Database for Dietary Studies 1.0 (FNDDS 1.0) and the Center for Nutrition Policy and Promotion food prices database were used for analysis. For 1387 foods, key variables were as follows: energy density (kcal/g), serving size (g), unit price ($/100 g), serving price ($/serving), and energy cost ($/kcal). A regression model tested associations between nutrients and unit price ($/100 g). Comparisons between food groups were tested by using one-factor analyses of variance. Relations between energy density and price within food groups were tested by using Spearman's correlations. Results: Grains and fats food groups supplied the lowest-cost dietary energy. The energy cost for vegetables was higher than that for any other food group except for fruit. Serving sizes increased with water content and varied inversely with energy density of foods. The highest prices per serving were for meats, poultry, and fish, and the lowest prices per serving were for the fats category. Although carbohydrates, sugar, and fat were associated with lower price per 100 g, protein, fiber, vitamins, and minerals were associated with higher price per 100 g, after adjustment for energy. Conclusions: Grains and sugars food groups were cheaper than vegetables and fruit per calorie and were cheaper than fruit per serving. These price differentials may help to explain why low-cost, energy-dense foods that are nutrient poor are associated with lower education and incomes.",
"title": "The cost of US foods as related to their nutritive value"
},
{
"docid": "MED-4299",
"text": "The evolution of the human diet over the past 10,000 years from a Paleolithic diet to our current modern pattern of intake has resulted in profound changes in feeding behavior. Shifts have occurred from diets high in fruits, vegetables, lean meats, and seafood to processed foods high in sodium and hydrogenated fats and low in fiber. These dietary changes have adversely affected dietary parameters known to be related to health, resulting in an increase in obesity and chronic disease, including cardiovascular disease (CVD), diabetes, and cancer. Some intervention trials using Paleolithic dietary patterns have shown promising results with favorable changes in CVD and diabetes risk factors. However, such benefits may be offset by disadvantages of the Paleolithic diet, which is low in vitamin D and calcium and high in fish potentially containing environmental toxins. More advantageous would be promotion of foods and food ingredients from our ancestral era that have been shown to possess health benefits in the form of functional foods. Many studies have investigated the health benefits of various functional food ingredients, including omega-3 fatty acids, polyphenols, fiber, and plant sterols. These bioactive compounds may help to prevent and reduce incidence of chronic diseases, which in turn could lead to health cost savings ranging from $2 to $3 billion per year as estimated by case studies using omega-3 and plant sterols as examples. Thus, public health benefits should result from promotion of the positive components of Paleolithic diets as functional foods.",
"title": "Evolution of the human diet: linking our ancestral diet to modern functional foods as a means of chronic disease prevention."
},
{
"docid": "MED-2973",
"text": "OBJECTIVE: Type 2 diabetes mellitus appears to involve an interaction between susceptible genetic backgrounds and environmental factors including highly calorific diets. As it is important to identify modifiable risk factors that may help reduce the risk of type 2 diabetes mellitus, the aim of the present study was to determine the association between egg consumption and the risk of type 2 diabetes mellitus. DESIGN: A specifically designed questionnaire was used to collect information on possible risk factors of type 2 diabetes mellitus. The odds ratios and 95 % confidence intervals for type 2 diabetes mellitus were calculated by conditional logistic regression. SETTING: A case-control study in a Lithuanian out-patient clinic was performed in 2001. SUBJECTS: A total of 234 cases with a newly confirmed diagnosis of type 2 diabetes mellitus and 468 controls free of the disease. RESULTS: Variables such as BMI, family history of diabetes, cigarette smoking, education, morning exercise and plasma TAG level were retained in multivariate logistic regression models as confounders because their inclusion changed the value of the odds ratio by more than 10 % in any exposure category. After adjustment for possible confounders more than twofold increased risk of type 2 diabetes mellitus was determined for individuals consuming 3-4·9 eggs/week (OR = 2·60; 95 % CI 1·34, 5·08) and threefold increased risk of the disease was determined for individuals consuming ≥5 eggs/week (OR = 3·02; 95 % CI 1·14, 7·98) compared with those eating <1 egg/week. CONCLUSIONS: Our data support a possible relationship of egg consumption and increased risk of type 2 diabetes mellitus.",
"title": "Egg consumption and the risk of type 2 diabetes mellitus: a case-control study."
},
{
"docid": "MED-4480",
"text": "Purpose To perform pattern analyses of dietary and lifestyle factors in relation to risk of esophageal and gastric cancers. Methods We evaluated risk factors for esophageal adenocarcinoma (EA), esophageal squamous cell carcinoma (ESCC), gastric cardia adenocarcinoma (GCA), and other gastric cancers (OGA) using data from a population-based case-control study conducted in Connecticut, New Jersey, and western Washington state. Dietary/lifestyle patterns were created using principal component analysis (PCA). Impact of the resultant scores on cancer risk was estimated through logistic regression. Results PCA identified six patterns: meat/nitrite, fruit/vegetable, smoking/alcohol, legume/meat alternate, GERD/BMI, and fish/vitamin C. Risk of each cancer under study increased with rising meat/nitrite score. Risk of EA increased with increasing GERD/BMI score, and risk of ESCC rose with increasing smoking/alcohol score and decreasing GERD/BMI score. Fruit/vegetable scores were inversely associated with EA, ESCC, and GCA. Conclusions PCA may provide a useful approach for summarizing extensive dietary/lifestyle data into fewer interpretable combinations that discriminate between cancer cases and controls. The analyses suggest that meat/nitrite intake is associated with elevated risk of each cancer under study, while fruit/vegetable intake reduces risk of EA, ESCC, and GCA. GERD/obesity were confirmed as risk factors for EA and smoking/alcohol as risk factors for ESCC.",
"title": "Principal component analysis of dietary and lifestyle patterns in relation to risk of subtypes of esophageal and gastric cancer"
},
{
"docid": "MED-2249",
"text": "High-level cadmium (Cd) exposure has long been known to induce nephropathy, severe osteoporosis, and fractures in humans. More recent epidemiology, however, reveals that, in populations not known to have important industrial exposure to this heavy metal, high-normal blood or urine Cd levels correlate with increased risk for vascular disorders, cancers, diabetes, and total mortality, as well as osteoporosis and nephropathy. Since these disorders appear unlikely to expedite Cd absorption, and since Cd has promoted these pathologies in rodent studies, it seems reasonable to conclude that Cd is an important mediating risk factor for these disorders in humans. Avoiding tobacco smoke or frequent ingestion of shellfish or organ meats can lessen humans exposure to Cd, but the chief dietary sources of Cd are plant-derived foods - green leafy vegetables, whole grains, tubers, and root vegetables - typically recommended for their health-supportive properties; indeed, among non-smokers, vegans tend to have the highest Cd body burden. Fortunately, iron sufficiency and ample dietary intakes of calcium, magnesium, and zinc can impede absorption of dietary Cd, both by down-regulating intestinal expression of mineral transporters, and by directly competing with Cd for access to these transporters. Correction of iron deficiency appears to be of particular importance for controlling Cd absorption. Moreover, zinc supplementation can counteract the toxicity of Cd already in the body via induction of metallothionein, which binds Cd avidly via its sulfhydryl groups; so long as it remains sequestered in this form, Cd is innocuous. Zinc supplementation may in any case be recommendable, as optimal zinc status exerts protective anti-inflammatory, antioxidant, and immunosupportive effects. Inasmuch as the toxicity of Cd appears to be mediated in large part by oxidative stress, ingestion of spirulina, lipoic acid, melatonin, and N-acetylcysteine may also have potential for mitigating the risk associated with Cd exposure, as suggested by rodent studies. Hence, although Cd may prove to be a major risk factor for morbidity and mortality in humans, practical strategies for limiting its absorption and pathogenic impact are at hand. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Zinc and multi-mineral supplementation should mitigate the pathogenic impact of cadmium exposure."
},
{
"docid": "MED-1403",
"text": "Background Several epidemiological studies have observed an increased risk of type 2 diabetes mellitus (T2DM) among subjects with a higher consumption of red and processed meat. Heme iron intake has been directly associated with a higher risk of T2DM in healthy adult Chinese and U.S populations. The objective of the present study was to evaluate the association between heme iron intake and the incidence of T2DM in a Mediterranean population at high cardiovascular risk. Methods We assessed a subset of participants in the PREDIMED trial as an observational cohort, followed up for a maximum of eight years. We initially included 1073 non-diabetic subjects (57.1% women) aged 67.3 ± 6.0 years, at high cardiovascular risk. Diet was assessed at the study baseline using a validated, semi-quantitative food frequency questionnaire. Results During the follow-up period 131 diabetics were newly diagnosed. The risk of developing T2DM was assessed using baseline heme iron intake and proportional hazard models, first unadjusted, then adjusted for energy, and finally adjusted for dietary, anthropometric, socio-demographic and lifestyle variables. Significant direct associations with the incidence of T2DM were found for heme iron (Hazard Ratio [HR] 1.30, 95% confidence interval [CI], 1.02 to 1.66). Secondarily, we have also observed that coffee (HR:0.93, 95% CI, 0.89 to 0.98) and alcoholic beverages (HR: 1.02, 95% CI, 1.01 to 1.04) were also found to reduce and increase the risk of T2DM, respectively. Conclusion High dietary intake of heme iron was associated with an increased risk of developing T2DM in a Mediterranean population at high cardiovascular risk. Trial registration Identifier: ISRCTN35739639.",
"title": "Heme iron intake and risk of new-onset diabetes in a Mediterranean population at high risk of cardiovascular disease: an observational cohort analysis"
},
{
"docid": "MED-4893",
"text": "Background Prospective studies evaluating associations between food intake and risk of heart failure (HF) in diverse populations are needed. Objectives Relationships between incident HF (death or hospitalization) and intake of seven food categories (whole grains, fruits/vegetables, fish, nuts, high-fat dairy, eggs, red meat) were investigated in an observational cohort of 14,153 African-American and white adults, age 45 to 64 years, sampled from four US communities. Methods Between baseline (1987–1989) and Exam 3 (1993–1995), dietary intake was based on responses to a 66-item food frequency questionnaire administered at baseline; thereafter, intake was based on averaged baseline and Exam 3 responses. Hazard ratios (HR [95% CI]) for HF were calculated per 1–daily serving difference in food group intake. Results During a mean of 13 years, 1,140 HF hospitalizations were identified. After multivariable adjustment (energy intake, demographics, lifestyle factors, prevalent cardiovascular disease, diabetes, hypertension), HF risk was lower with greater whole-grain intake (0.93 [0.87, 0.99]), but HF risk was higher with greater intake of eggs (1.23 [1.08, 1.41]) and high-fat dairy (1.08 [1.01, 1.16]). These associations remained significant independent of intakes of the five other food categories, which were not associated with HF. Conclusions In this large, population-based sample of African-American and white adults, whole-grain intake was associated with lower HF risk, whereas intake of eggs and high-fat dairy were associated with greater HF risk after adjustment for several confounders.",
"title": "Incident Heart Failure Is Associated with Lower Whole-Grain Intake and Greater High-Fat Dairy and Egg Intake in the Atherosclerosis Risk in Communities (ARIC) Study"
},
{
"docid": "MED-1254",
"text": "OBJECTIVE: To investigate the effect of replacing lean meat with a soy product, tofu, on coronary heart disease risk factors including serum lipoproteins, lipoprotein (a), factor VII, fibrinogen and in vitro susceptibility of LDL to oxidation. DESIGN: A randomized cross over dietary intervention study. SETTING: Free-living individuals studied at Deakin University. SUBJECTS: Forty-five free-living healthy males aged 35 to 62 years completed the dietary intervention. Three subjects were non-compliant and excluded prior to analysis. INTERVENTIONS: A diet containing 150 grams of lean meat per day was compared to a diet containing 290 grams of tofu per day in an isocaloric and isoprotein substitution. Each dietary period was one month duration. RESULTS: Analysis of the seven-day diet record showed that diets were similar in energy, protein, carbohydrate, total fat, saturated and unsaturated fat, polyunsaturated to saturated fat ratio, alcohol and fiber. Total cholesterol and triglycerides were significantly lower, and in vitro LDL oxidation lag phase was significantly longer on the tofu diet compared to the meat diet. The hemostatic factors, factor VII and fibrinogen, and lipoprotein(a) were not significantly affected by the tofu diet. CONCLUSIONS: The increase in LDL oxidation lag phase would be expected to be associated with a decrease in coronary heart disease risk.",
"title": "Effect of meat replacement by tofu on CHD risk factors including copper induced LDL oxidation."
},
{
"docid": "MED-1323",
"text": "Background: Fat and protein sources may influence whether low-carbohydrate diets are associated with type 2 diabetes (T2D). Objective: The objective was to compare the associations of 3 low-carbohydrate diet scores with incident T2D. Design: A prospective cohort study was conducted in participants from the Health Professionals Follow-Up Study who were free of T2D, cardiovascular disease, or cancer at baseline (n = 40,475) for up to 20 y. Cumulative averages of 3 low-carbohydrate diet scores (high total protein and fat, high animal protein and fat, and high vegetable protein and fat) were calculated every 4 y from food-frequency questionnaires and were associated with incident T2D by using Cox models. Results: We documented 2689 cases of T2D during follow-up. After adjustments for age, smoking, physical activity, coffee intake, alcohol intake, family history of T2D, total energy intake, and body mass index, the score for high animal protein and fat was associated with an increased risk of T2D [top compared with bottom quintile; hazard ratio (HR): 1.37; 95% CI: 1.20, 1.58; P for trend < 0.01]. Adjustment for red and processed meat attenuated this association (HR: 1.11; 95% CI: 0.95, 1.30; P for trend = 0.20). A high score for vegetable protein and fat was not significantly associated with the risk of T2D overall but was inversely associated with T2D in men aged <65 y (HR: 0.78; 95% CI: 0.66, 0.92; P for trend = 0.01, P for interaction = 0.01). Conclusions: A score representing a low-carbohydrate diet high in animal protein and fat was positively associated with the risk of T2D in men. Low-carbohydrate diets should obtain protein and fat from foods other than red and processed meat.",
"title": "Low-carbohydrate diet scores and risk of type 2 diabetes in men"
}
] |
36
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Starting a large business with a not so large income?
|
[
{
"docid": "368649",
"text": "\"For example, Biff Spoiles started an animation studio and production developing company to produce animations -- something in the ballpark of $12,000,000.00 U.S.D. -- and he had a $12K/yearly salary. I have no clue what you mean, as others have mentioned. (I'm not sure what the \"\"12 million\"\" refers to? Do you mean \"\"total cost of animations created by the company in a year\"\" or? If so, \"\"12 million\"\" would amount to say 5 to 20 major, brand name TV commercials, for example. Do you mean the \"\"cost of plant\"\" - so, for a \"\"TV commercial production company\"\" you mean purchasing desks, drawing pads, Porsches, and so on?) Your specific example of a \"\"film or TV-commercial production company\"\" is a bad example, it's not really a \"\"business\"\" - that is to say, it does not rely on capital and return on capital. The way famous \"\"film or TV-commercial production companies\"\" happens is precisely like this: A young guy/girl G (perhaps a designer or filmmaker) is working, just as you say, for a menial wage at a film company. (G got that first job perhaps out of art school.) G gets a chance at doing a photo shoot, animation, or helping direct a TV commercial. G does a fantastic job. Later that year, a large important animation or commercial job arrives at the company; due to the earlier excellent result, G is allowed to work on the new one. G again he does a fantastic job. Soon, within that company, G is a highly-regarded animator or director and has attracted fame amongst colleagues and clients. Eventually, G hears of a company (XYZ Hotel) that needs a TV ad made. (Or an animation, or whatever.) G says to XYZ, look, you could spend $230,000 with a production company, and in reality they'd have me direct it anyway. I'm leaving to work independently, so I will do your job for only $190,000. In a word, XYZ says \"\"Yes\"\" and hands over a cheque for $190,000. G spends $160,000 on the usual actors, cameramen, editing, etc, and uses 2 months of G's own time, and pockets $5000 after tax. G then doesn't get a job for a couple months, and then gets three more in the new year. Because the commercial for XYZ was so good, XYZ gave him another couple to do, for another product line. Eventually G has just enough money coming in that he \"\"hires\"\" a few freelance people for a few weeks here and there ... a cameraman, illustrator, gopher, and so on. Eventually G has enough TV ads solidly booked G can risk actually hiring long-time friend P as a producer. P spends most of her time actually bringing in more work - and it builds from there. Eventually. You have a very busy, well-known in the industry, TV commercial production company with many staff and endless clients (example, say, http://rsafilms.com) It might be at some point in there (say, around year three), G would like to borrow the odd million bucks to basically \"\"help with cashflow.\"\" The answer to that is nothing more than \"\"through business contacts, G knows a wealthy dentist/whoever who is prepared to do that.\"\" But note carefully that at that point, G's company is already very firmly established, famous for doing 20 spectacular animations/commercials, and so on. (Note too that 999 times out of 1000 when this happens, the money evaporates and the dentist D never sees a penny back. In that case G \"\"apologizes\"\".) Only much much later once the company has many, many staff and great cashflow, could the production company actually borrow from a bank, or perhaps from \"\"actual investors\"\", which is more what you have in mind. regarding your four categories. Numbers 1 and 3 are totally wrong; they do not work at all like you are asking. indeed the very simple answer is: \"\"borrow money\"\" to start a category 1 or 3 type of business. It's totally inconceivable. (The only exception would be if you literally just have an extremely rich Uncle, who loans you a few million to \"\"start an animation studio\"\" - which would be completely whacky. Because in that example: company XYZ could not care less if you \"\"have\"\" an animation studio (ie: your Uncle has given you a platinum card, and you bought a building, some drawing pads, and a few dozen Macs). XYZ just couldn't care less. All they care about is your folio of work. In this example, RSA would get the job :) ) My guess is you're thinking people somehow magically go around \"\"borrowing money\"\" to get businesses like that started. (Your examples 1 and 3.) The simple answer is they don't and can't - your fears are assuaged! :)\"",
"title": ""
},
{
"docid": "275249",
"text": "\"There are three (or four) ways that a company can grow: (Crowdfunding is a relatively new (in mainstream businesses) alternative financing method where people will finance a company with the expectation that they will benefit from the product or service that they provide.) Obviously a startup has no prior income to use, so it must either raise money through equity or debt. People say that one must borrow contingent on their salary. Banks lend money based on the ability to pay the loan back plus interest. For individuals, their income is their primary source of cash flow, so, yes, it is usually the determining factor in getting a loan. For a business the key factor is future cash flows. So a business will borrow money, say, to buy a new asset (like a factory) that will be used to generate cash flows in the future so that they can pay down the debt. If the bank believes that the use of the money is going to be profitable enough that they will get their money back with interest, they'll loan the money. Equity investors are essentially the same, but since they don't get a guaranteed payback (they only get paid through non-guaranteed dividends or liquidation), their risk is higher and they are looking for higher expected returns. So the question I'd have as a bank or equity investor is \"\"what are you going to do with the money?\"\" What is your business strategy? What are you going to do that will make profits in the future? Do you have a special idea or skill that you can turn into a profitable business? (Crowdfunding would be similar - people are willing to give you money based on either the social or personal benefit of some product or service.) So any business either starts small and grows over time (which is how the vast majority of businesses grow), or has some special idea, asset, skill, or something that would make a bank willing to take a risk on a huge loan. I know, again, that people here tend to turn blind eyes on unfortunate realities, but people do make giant businesses without having giant incomes. The \"\"unfortunate reality\"\" is that most startups fail. Which may sound bad, but also keep in mind that most startups are created by people that are OK with failing. They are people that are willing to fail 9 times with the thought that the 10th one will take off and make up for the losses of the first 9. So I would say - if you have some great idea or skill and a viable strategy and plan to take it to market, then GO FOR IT. You don't need a huge salary to start off. You need something that you can take to market and make money. Most people (myself included) either do not have that idea or skill to go out on their own, or don't have the courage to take that kind of risk. But don't go in assuming all you need is a loan and you'll be an instant millionaire. You might, but the odds are very long.\"",
"title": ""
}
] |
[
{
"docid": "158258",
"text": "\"The uncertainty as I see it is around **personal** income tax rates and the **employee** portion of the SS tax. This has nothing to do with the operating costs of large businesses, right? Small businesses often have their taxes done essentially on the owner's personal return, so in those cases the personal income tax rate affects them. This article talks about large businesses who are fussing about the \"\"uncertainty\"\". Why is this uncertainty about things like taxes treated like something new? Historically tax rates have bounced around, and in the past taxes have been higher. The SS tax cut is a very recent thing, but now that's it in place suddenly people can't imagine hiring if it goes back to what it was for many years. Also, the SS tax cut is on the employee portion, so even if it goes back the employer contribution doesn't change? WTF are they talking about? This sounds more like silly people being confused by partisan talking points.\"",
"title": ""
},
{
"docid": "580542",
"text": "> Google would be forced to actually compete with companies vs. Giving everything away free. That creates employment opportunities for other startups to compete in a fair environment vs. Trying to acquire millions of users on no revenue. TL;DR Don't blame business, blame the politics that let bad business happen. Business doesn't work like that, specially for a publicly traded company. 'Free' goods or services are used as a loss leader to drive their profits in other sectors of the company. Whether it's for PR, marketing, or sales, no company drives their business at a loss. Somewhere, somehow the free things they do are driving their business towards higher profitability. Money isn't being lost on the economy by providing these things as free, it's just being used in different ways. Sure it could be used to pay for the wages of an employee at a startup which provides the same service... but if Google is providing it at or below the most efficient market price then it would be *wasting* money to have less efficient companies providing essentially the same product or service. That money could instead be used in more profitable sectors of the economy, which could in turn generate a healthier and/or faster growing economy overall. Working smarter, not harder. Secondly, startups aren't designed for profitability in the first few years of their operations. They're designed to capture users and information (or as patent holders but that's largely unrelated to my main point) that can later be acquired by larger companies who are looking to target those users. Why else would any company pay for a startup while they're operating at a loss? The revenue for startups comes much later on as they're bought out by bigger companies or they find a way to monetize their user base/generate stable sources of revenue. If your argument is that employment by start ups drives the economy at large, I have to ask, if the economy is operating less efficiently (by supporting start ups in replacing the market share currently held by much more efficiently operating large companies ~) by employing more people, how is this healthier for the economy as a whole? Supporting start ups is good but it has to be done in such a way that it doesn't hurt existing business just for the sake of making jobs. The size of a company doesn't make them bad as long as they compete fairly with everyone else in the market. ~ caveat being where large companies do not form an oligopoly (ie Comcast, TWC, etc...) which is obviously inefficient to begin with which is largely a product of bad politics rather than market forces",
"title": ""
},
{
"docid": "568629",
"text": "Wow! First, congratulations! You are both making great money. You should be able to reach your goals. Are we on the right track ? Are we doing any mistakes which we could have avoided ? Please advice if there is something that we should focus more into ! I would prioritize as follows: Get on the same page. My first red flag is that you are listing your assets separately. You and your wife own property together and are raising your daughter together. The first thing is to both be on the same page with your combined income and assets. This is critical. Set specific goals for the future. Dreaming and big-picture life planning will be the foundation for building a detailed plan for reaching your goals. You will see more progress with more sacrifice. If you both are not equally excited about the goals, you will not both be equally willing to sacrifice lifestyle now. You have the income now to be able to set yourselves up to do whatever you want in 10 years, if you can agree on what you want. Hire a financial planner you trust. Interview people, ask someone who is where you want to be in 10 years. You need someone with experience that can guide you through these questions and understands how to manage your income stream. Start saving for retirement in tax-advantaged accounts. This should be as much as 10%-15% of your income combined, so $30k-$45k per year. You need to start diversifying your investments. Real estate is great, but I would never recommend it as this large a percentage of net worth. Start saving for your child's education. Hard to say what you need here, since I don't know your goals. A financial planner should assist you with this. Get rid of your debt. Out of your $2.1M of rental real estate and land, you have $1.4M of debt. It will be difficult to start a business with that much additional debt. It will also put stress on your retirement that you don't need. You are taking on lots of risk here. I would sell all but maybe one of the properties and let it cash flow. This will free up cash to start investing for retirement or future business too. Buy more rental in the future with cash only. You have plenty of income to do it this way, and you will be setting yourself up for a great future. At this point you can continue to pile funds into any/all your investments, with the goal of using the funds to start a business or to live on. If all your investments are tied up in real estate, you wont have anything to draw on if needed for a business opportunity. You need to weigh this out in your goal and planning. What should we do to prepare for a comfortable retirement and safety You cannot plan for or see all scenarios. However, good planning will give you more options and more choices. Investing driven by fear will set you up for failure. Spend less than you make. Be patient. Be generous. Cheers!",
"title": ""
},
{
"docid": "65180",
"text": "You're off to a great start. Here are the steps I would take: 1.) Pay off any high-interest debt. 2.) Keep six to twelve months in a highly liquid emergency fund. If the banks aren't safe, also consider having one or two months of cash or cash-equivalents on the premises. 3.) Rent a larger apartment, if possible, until you've saved more. The cost of the land and construction will consume a very large portion of your net worth. Given the historical political instability in that region, mentioned by the previous comments, I would hesitate to put such a large percentage of your wealth in to real estate. 4.) Get a brokerage account that's insured and well known. If you're willing to take the five percent hit to move assets offshore, then consider Vanguard. I'm not sure if they'll give you an account but they're generally acknowledged as an amazing broker in the US with low fees and amazing funds. Five percent (12,500) is worth it in my opinion. As you accumulate more wealth, you can stop moving cash overseas and keep a larger mix domestically. 5.) Invest in your business and yourself even more. As far as finding new investment opportunities, I would go through the list of all the typical major asset classes and consider the pros and cons: fixed-income, stocks, currencies, real estate / REITs, own a small business, commodities etc.,",
"title": ""
},
{
"docid": "71766",
"text": ">Would you take on somebody if you seriously thought this was going to happen? Would any small enterprise ever hire anyone? Equality is a nice idea but it will stifle small and slow growing businesses to the point where the only way to get started will be to take a big loan. And that is not in the interests of the economy at large. Don't worry, there is a large number of people out there who, if they get their way, would make it illegal not to hire these people. I'm all for workers' rights, but once the pendulum swings so far in favor of the employee that it becomes detrimental to hire them unemployment is going to go up.",
"title": ""
},
{
"docid": "141458",
"text": "\"Not really, no. The assumption you're making—withdrawals from a corporation are subject to \"\"[ordinary] income tax\"\"—is simplistic. \"\"Income tax\"\" encompasses many taxes, some more benign than others, owing to credits and exemptions based on the kind of income. Moreover, the choices you listed as benefits in the sole-proprietor case—the RRSP, the TFSA, and capital gains treatment for non-registered investments—all remain open to the owner of a small corporation ... the RRSP to the extent that the owner has received salary to create contribution room. A corporation can even, at some expense, establish a defined benefit (DB) pension plan and exceed individual RRSP contribution limits. Yes, there is a more tax-efficient way for small business owners to benefit when it comes time to retirement. Here is an outline of two things I'm aware of: If your retirement withdrawals from your Canadian small business corporation would constitute withdrawal from the corporation's retained earnings (profits), i.e. income to the corporation that had already been subject to corporate income tax in prior years, then the corporation is able to declare such distributions as dividends and issue you a T5 slip (Statement of Investment Income) instead of a T4 slip (Statement of Remuneration Paid). Dividends received by Canadian residents from Canadian corporations benefit from the Dividend Tax Credit (DTC), which substantially increases the amount of income you can receive without incurring income tax. See TaxTips.ca - Non-eligible (small business) dividend tax credit (DTC). Quote: For a single individual with no income other than taxable Canadian dividends which are eligible for the small business dividend tax credit, in 2014 approximately $35,551 [...] could be earned before any federal* taxes were payable. * Provincial DTCs vary, and so combined federal/provincial maximums vary. See here. If you're wondering about \"\"non-eligible\"\" vs. \"\"eligible\"\": private small business corporation dividends are generally considered non-eligible for the best DTC benefit—but they get some benefit—while a large public corporation's dividends would generally be considered eligible. Eligible/non-eligible has to do with the corporation's own income tax rates; since Canadian small businesses already get a big tax break that large companies don't enjoy, the DTC for small businesses isn't as good as the DTC for public company dividends. Finally, even if there is hardly any same-year income tax advantage in taking dividends over salary from an active small business corporation (when you factor in both the income tax paid by the corporation and the individual), dividends still allow a business owner to smooth his income over time, which can result in a lower lifetime average tax rate. So you can use your business as a retained earnings piggy bank to spin off dividends that attract less tax than ordinary income. But! ... if you can convince somebody to buy your business from you, then you can benefit from the lifetime capital gains exemption of up to $800,000 on qualifying small business shares. i.e. you can receive up to $800K tax-free on the sale of your small business shares. This lifetime capital gains exemption is a big carrot—designed, I believe, to incentivize Canadian entrepreneurs to develop going-concern businesses that have value beyond their own time in the business. This means building things that would make your business worth buying, e.g. a valued brand or product, a customer base, intellectual property, etc. Of course, there are details and conditions with all of what I described, and I am not an accountant, so please consult a qualified, conflict-free professional if you need advice specific to your situation.\"",
"title": ""
},
{
"docid": "156554",
"text": "\"This is a great question! I've been an entrepreneur and small business owner for 20+ years and have started small businesses in 3 states that grew into nice income streams for me. I've lived off these businesses for 20+ years, so I know it can be done! First let me start by saying that the rules, regulations, requirements and laws for operating a business (small or large) legally, for the most part, are local laws and regulations. Depending on what your business does, you may have some federal rules to follow, but for the most part, it will be your locality (state, county, city) that determines what you'll have to do to comply and be \"\"legal\"\". Also, though it might be better in some cases to incorporate (and even required in some circumstances), you don't always have to. There are many small businesses (think landscapers, housekeepers, babysitters, etc.) that get income from their \"\"business operations\"\" and do so as \"\"individuals\"\". Of course, everyone has to pay taxes - so as long as you property record your income (and expenses) and properly file your tax returns every year, you are \"\"income tax legal\"\". I won't try to answer the income tax question here, though, as that can be a big question. Also, though you certainly can start a business on your own without hiring lawyers or other professionals (more on that below), when it comes to taxes, I definitely recommend you indeed plan to hire a tax professional (even if it's something like H&R Block or Jackson Hewitt, etc). In some cities, there might even be \"\"free\"\" tax preparation services by certain organizations that want to help the community and these are often available even to small businesses. In general, income taxes can be complicated and the rules are always changing. I've found that most small business owners that try to file their own taxes generally end up paying a lot more taxes than they're required to, in essence, they are overpaying! Running a business (and making a profit) can be hard enough, so on to of that, you don't need to be paying more than you are required to! Also, I am going to assume that since it sounds like it would be a business of one (you), that you won't have a Payroll. That is another area that can be complicated for sure. Ok, with those generics out of the way, let me tackle your questions related to starting and operating a business, since you have the \"\"idea for your business\"\" pretty figured out. Will you have to pay any substantial amount of money to attorneys or advisors or accountants or to register with the government? Not necessarily. Since the rules for operating a business legally vary by your operating location (where you will be providing the service or performing your work), you can certainly research this on your own. It might take a little time, but it's doable if you stick with it. Some resources: The state of Florida (where I live) has an excellent page at: http://www.myflorida.com/taxonomy/business/starting%20a%20business%20in%20florida/ You might not be in Florida, but almost every state will have something similar. What all do I need to do to remain on the right side of the law and the smart side of business? All of the answers above still apply to this question, but here are a few more items to consider: You will want to keep good records of all expenses directly related to the business. If you license some content (stock images) for example, you'll want to document receipts. These are easy usually as you know \"\"directly\"\". If you subscribe to the Apple Developer program (which you'll need to if you intend to sell Apps in the Apple App Stores), the subscription is an expense against your business income, etc. You will want to keep good records of indirect costs. These are not so easy to \"\"figure out\"\" (and where a good accountant will help you when this becomes significant) but these are important and a lot of business owners hurt themselves by not considering these. What do I mean? Well, you need an \"\"office\"\" in order to produce your work, right? You might need a computer, a phone, internet, electricity, heat, etc. all of which allow you to create a \"\"working environment\"\" that allows you to \"\"produce your product\"\". The IRS (and state tax authorities) all provide ways for you to quantify these and \"\"count them\"\" as legitimate business expenses. No, you can't use 100% of your electric bill (since your office might be inside your home, and the entire bill is not \"\"just\"\" for your business) but you are certainly entitled to some part of that bill to count as a business expense. Again, I don't want to get too far down the INCOME TAX rabbit hole, but you still need to keep track of what you spend! You must keep good record of ALL your income. This is especially important when you have money coming in from various sources (a payroll, gifts from friends, business income from clients and/or the App Stores, etc.) Do not just assume that copies of your bank deposits tell the whole story. Bank statements might tell you the amount and date of a deposit, but you don't really know \"\"where\"\" that money came from unless you are tracking it! The good news is that the above record keeping can be quite easy with something like Quicken or QuickBooks (or many many other such popular programs.) You will want to ensure you have the needed licenses (not necessarily required at all for a lot of small businesses, especially home based businesses.) Depending on your business activity, you might want to consider business liability insurance. Again, this will depend on your clients and/or other business entities you'll be dealing with. Some might require you to have some insurance. Will be efforts even be considered a business initially until some amount of money actually starts coming in? This might be a legal / accountant question as to the very specific answer from the POV of the law and taxing authorities. However, consider that not all businesses make any money at all, for a long time, and they definitely \"\"are a business\"\". For instance, Twitter was losing money for a long time (years) and no one would argue they were not a business. Again, deferring to the attorneys/cpas here for the legal answer, the practical answer is that you're performing \"\"some\"\" business activity when you start creating a product and working hard to make it happen! I would consider \"\"acting as\"\" a business regardless! What things do I need to do up-front and what things can I defer to later, especially in light of the fact that it might be several months to a couple years before any substantial income starts coming in? This question's answer could be quite long. There are potentially many items you can defer. However, one I can say is that you might consider deferring incorporation. An individual can perform a business activity and draw income from it legally in a lot of situations. (For tax purposes, this is sometimes referred to as \"\"Schedule-C\"\" income.) I'm not saying incorporation is a bad thing (it can shield you from a lot of issues), but I am saying that it's not necessary on day 1 for a lot of small businesses. Having said that, this too can be easy to do on your own. Many companies offer services so you can incorporate for a few hundred dollars. If you do incorporate, as a small business of one person, I would definitely consider a tax concept called an \"\"S-Corp\"\" to avoid paying double taxes.) But here too, we've gone down the tax rabbit hole again. :-)\"",
"title": ""
},
{
"docid": "81343",
"text": "\"I disagree with the selected answer. There's no one rule of thumb and certainly not simple ones like \"\"20 cents of every dollar if you're 35\"\". You've made a good start by making a budget of your expected expenses. If you read the Mr. Money Mustache blogpost titled The Shockingly Simple Math Behind Early Retirement, you will understand that it is usually a mistake to think of your expenses as a fixed percentage of your income. In most cases, it makes more sense to keep your expenses as low as possible, regardless of your actual income. In the financial independence community, it is a common principle that one typically needs 25-30 times one's annual spending to have enough money to sustain oneself forever off the investment returns that those savings generate (this is based on the assumption of a 7% average annual return, 4% after inflation). So the real answer to your question is this: UPDATE Keats brought to my attention that this formula doesn't work that well when the savings rates are low (20% range). This is because it assumes that money you save earns no returns for the entire period that you are saving. This is obviously not true; investment returns should also count toward your 25-times annual spending goal. For that reason, it's probably better to refer to the blog post that I linked to in the answer above for precise calculations. That's where I got the \"\"37 years at 20% savings rate\"\" figure from. Depending on how large and small x and y are, you could have enough saved up to retire in 7 years (at a 75% savings rate), 17 years (at a 50% savings rate), or 37 years! (at the suggested 20% savings rate for 35-year olds). As you go through life, your expenses may increase (eg. starting a family, starting a new business, unexpected health event etc) or decrease (kid wins full scholarship to college). So could your income. However, in general, you should negotiate the highest salary possible (if you are salaried), use the 25x rule, and consider your life and career goals to decide how much you want to save. And stop thinking of expenses as a percentage of income.\"",
"title": ""
},
{
"docid": "514697",
"text": "\"Is it not that bad? Depends how bad is bad. The problems causes by a government having large debt are similar to those caused by an individual having large debt. The big issue is: More and more of your income goes to paying interest on the debt, and is thus not available for spending on goods and services. If it gets bad enough, you find you cannot make payments, you start defaulting on loans, and then you have to make serious sacrifices, like selling your property to pay the debt. Nations have an advantage over individuals in that they can sometimes repudiate debt, i.e. simply declare that they are not going to pay. Lenders can then refuse to give them more money, but that doesn't get their original loans paid back. In theory other nations could send in troops to seize property to pay the loan, but this is a very extreme solution. Totally aside from any moral considerations, modern warfare is very expensive, it's likely the war would cost you more than you'd recover on the debt. How much debt is too much? It's hard to give a number, any more than one could give a \"\"maximum acceptable debt\"\" for an individual. American banks have a rule of thumb that they won't normally loan you money if your total debt payments would be more than 1/3 of your income. I've never come close to that, that seems awfully high to me. But, say, a young person just starting out so he's not making a lot of money, and he lives someplace with high housing prices, might find this painful but acceptable. Etc.\"",
"title": ""
},
{
"docid": "470513",
"text": "It's difficult to provide an exact answer as this will very much depend on the bank & the local regulatory scheme. However as a business owner you should be able to provide incorporation docs, some proof of ownership of the company and last years' financial statements or tax returns, many banks would accept this as a proof of income for the purposes of granting credit. In general in most jurisdictions I can think of, a high downpayment will not remove the need to verify income as the bank needs to feel comfortable that you have the ability to pay the remaining 25% (e.g. how do they know you're not a serially unemployed lottery winner) and if the downpayment is quite large they may want some assurance that you got the money legally (e.g. how do they make sure you're not a drug dealer). So probably regardless of how large a downpayment most banks would probably want some additional proofs of income however what proofs are needed may be more flexible than just a salary stub. I suggest taking a look at what sort of documents you may have on hand that can serve to validate your revenue in some way and contacting a few banks directly to see what options they can provide and whether some custom-tailored arrangement can be made.",
"title": ""
},
{
"docid": "358196",
"text": "One significant reason it makes sense for filing to be the default is home ownership rates. I think far more so than investment income, Americans own homes: as there is a significant mortgage interest deduction, between that and investments a large number of Americans would have to file (about a third of Americans get the mortgage interest tax deduction, and a large chunk of the richest don't qualify but would have to file for investments anyway). We also have a very complicated tax code, with nearly everyone getting some kind of deduction. Earned Income Tax Credit for the working poor (folks making, say, $30k for a family of 4 with a full-time job get several thousand dollars in refundable credits, for example), the Student Loan interest deduction, the above mortgage deduction, almost everyone gets something. Finally, your employer may not know about your family situation. As we have tax credits and deductions for families based on number of children, for example, it's possible your employer doesn't know about those (if you don't get health insurance on their behalf, they may well not know). Start reporting things like that separately... and you end up with about as much work as filing is now.",
"title": ""
},
{
"docid": "15844",
"text": "\"Look for states that have no income tax. A lot of these states supplement their revenue with higher property taxes, but if you rent and do not own property in the state, then you will have no state tax liability. Similarly, many states treat capital gains no differently than income tax, so if you make your earnings due to a large nest egg, then way you will still incur no tax liability on the state level Look for \"\"unincorporated\"\" areas, as these are administrative divisions of states that do not have a municipal government, and as such do not collect local taxes. Look for economic development perks of the new jurisdiction. Many states have some kind of formal tax credit for people that start business or buy in certain areas, but MONEY TALKS and you can make an individual arrangement with any agency, municipality etc. If the secretary at city hall doesn't know about a prepackaged formal arrangement that is offered to citizens, then ask for the \"\"expedited development package\"\" which generally has a \"\"processing fee\"\" involved. This is something you make up ie. \"\"What is the processing fee for the expedited development package, quote on quote\"\" States like Maryland and Nevada have formalized this process, but you are generally paying off the Secretary of State for favorable treatment. You'll always be paying off someone.\"",
"title": ""
},
{
"docid": "263197",
"text": "I think that you should be very careful who you label a neo-nazi and you should be very careful what other people you decide to exclude in the future. If someone is conducting business in a professional manner, then why deprive them of the opportunity? When large companies leverage their market positions like that I start to wonder if they're too large.",
"title": ""
},
{
"docid": "153375",
"text": "I know some companies or entities have large incomes or expenses at certain times of the year, and like to close their books after these large events. For example where I work, the primary seasonal income comes after summer, so our fiscal year ends at the last days of October. This gives the accountants enough time to collect all the funds, reconcile whatever they have to, pay off whatever they have to and get working on a budget for the next year sooner than a calendar year would. There also might be tax reasons. To get all of your income at the beginning of your fiscal year, even if that is in the middle of the calendar year would allow a company to plan large deductible investments with more certainty. I am not to sure of the tax reasons.",
"title": ""
},
{
"docid": "266229",
"text": "\"The HMRC has a dedicated self-help/learning site that is helpful here: It's important to tell HMRC that you are self-employed as soon as possible. If you don't, you may have to pay a penalty. You don't want to pay more to HMRC than you have to as it is a waste of your money. Your business has started when you start to advertise or you have a customer to buy your goods or services. It is at this point that your business is 'trading'. You cannot register before you start trading. For example, if you advertise your business in the local newspaper on 15 January but do not get your first customer until 29 March; in this case, you have been trading since 15 January. You must tell HMRC within six months of the end of the tax year in which you start self-employment. You must therefore register by 5 October. But it's best to register well before this so that you do not forget to do so. The HMRC also has a YouTube channel with help videos, and \"\"Am I Trading or Not?\"\" might be of particular interest to you. Most of the registration is based around the concept of starting to work with the intent to make a profit. By the letter of law and regulations, you should register within six months of the end of the tax year you started to avoid any potential penalty. However note that the situation is different based upon your intent. If you begin making/putting up videos online as a hobby with the hope that you can make something to help you defray the basic costs involved, and the total amount you make is relatively small (say, less than 500 pounds), you will not be classified as \"\"trading\"\" and likely have no need to register with HMRC. As soon as you begin to get in regular payments, maybe a single payment of a significant size, or multiple payments for a similar service/item, you are vastly more likely to need to register. From my reading you would likely be safe to begin putting up videos without registration, but if you begin spending a large portion of your time over an extended period (multiple months) and/or begin getting payments of any notable size then you should likely register with the appropriate services (HMRC, etc). As is the case in both the USA and UK, simple registration is pretty cheap and the costs of little/no income are usually pretty minor. Also note that the HMRC trading and self-employment regulations are unusual compared to many US laws/institutions, in that you are explicitly permitted to begin doing something and only register later. So if you start doing videos for an entire tax year + 5 months and make nothing significant, you'd seemingly be fine to never register at all.\"",
"title": ""
},
{
"docid": "545419",
"text": "\"That's right. It is the far right that have fought Medicare and single payer health insurance from the 70s. Ronald Reagan famously recorded a LP deriding Medicare as the slippery slope to socialism. Health insurance is a tool large corporations use to #1 keep employees frightened of losing their job and #2 discouraging employees from leaving their \"\"organization\"\" and starting a small business that will compete with them. It is anything but a \"\"poorly\"\" thought out policy. If large corporations felt it was bad for business they would join the fight for single payer which would relieve them of one hell of an expense. They could save Billions! but they don't because they want it this way. It must be worth a lot of money to them.\"",
"title": ""
},
{
"docid": "338700",
"text": "It sounds like something is getting lost in translation here. A business owner should not have to pay personal income tax on business expenses, with the caveat that they are truly business expenses. Here's an example where what you described could happen: Suppose a business has $200K in revenue, and $150K in legitimate business expenses (wages and owner salaries, taxes, services, products/goods, etc.) The profit for this example business is $50K. Depending on how the business is structured (sole proprietor, llc, s-corp, etc), the business owner(s) may have to pay personal income tax on the $50K in profit. If the owner then decided to have the business purchase a new vehicle solely for personal use with, say, $25K of that profit, then the owner may think he could avoid paying income tax on $25K of the $50K. However, this would not be considered a legitimate business expense, and therefore would have to be reclassified as personal income and would be taxed as if the $25K was paid to the owner. If the vehicle truly was used for legitimate business purposes then the business expenses would end up being $175K, with $25K left as profit which is taxable to the owners. Note: this is an oversimplification as it's oftentimes the case that vehicles are partially used for business instead of all or nothing. In fact, large items such as vehicles are typically depreciated so the full purchase price could not be deducted in a single year. If many of the purchases are depreciated items instead of deductions, then this could explain why it appears that the business expenses are being taxed. It's not a tax on the expense, but on the income that hasn't been reduced by expenses, since only a portion of the big ticket item can be treated as an expense in a single year.",
"title": ""
},
{
"docid": "87480",
"text": "I agree but... ( i didn't read the article in its entirety!) but if her business was grossing $300k per year... and for her to fall so hard in such a short time, tells me that even with such a large income, she was still living beyond her means.",
"title": ""
},
{
"docid": "295738",
"text": "\"Financial statements provide a large amount of specialized, complex, information about the company. If you know how to process the statements, and can place the info they provide in context with other significant information you have about the market, then you will likely be able to make better decisions about the company. If you don't know how to process them, you're much more likely to obtain incomplete or misleading information, and end up making worse decisions than you would have before you started reading. You might, for example, figure out that the company is gaining significant debt, but might be missing significant information about new regulations which caused a one time larger than normal tax payment for all companies in the industry you're investing in, matching the debt increase. Or you might see a large litigation related spending, without knowing that it's lower than usual for the industry. It's a chicken-and-egg problem - if you know how to process them, and how to use the information, then you already have the answer to your question. I'd say, the more important question to ask is: \"\"Do I have the time and resources necessary to learn enough about how businesses run, and about the market I'm investing in, so that financial statements become useful to me?\"\" If you do have the time, and resources, do it, it's worth the trouble. I'd advise in starting at the industry/business end of things, though, and only switching to obtaining information from the financial statements once you already have a good idea what you'll be using it for.\"",
"title": ""
},
{
"docid": "583040",
"text": "The short answer is that you can use student loans for living expenses. Joe provides a nice taxonomy of loans. I would just add that some loans are not only guaranteed, but also subsidized. Essentially the Government buys down the rate of the loan. The mechanics are that a financial aid package might consist of grants, work study (job), subsidized, and guaranteed loans. One can turn down one or more of the elements of the package. All will be limited in some form. The work study will have a maximum number of hours and generally has low pay. Many find better deals working in the businesses surrounding the college or starting their own services type business. The grants rarely cover the full cost of tuition and books. The loans will both be limited in amount. It mainly depends on what you qualify for, and generally speaking the lower the income the more aid one qualifies for. Now some students use all their grant, all their loan money and buy things that are not necessary. For example are you going to live in the $450/month dorm, or the new fancy apartments that are running $800/month? Are you going to use the student loan money to buy a car? Will it be a new BMW or a 8 year old Camary? I see this first hand as I live near a large university. The pubs are filled with college students, not working, but drinking and eating every night. Many of them drive very fancy cars. The most onerous example of this is students at the military academies. Attendees have their books and tuition completely paid for. They also receive a stipend, and more money can be earned over the summer. They also all qualify for a 35K student loan in their junior year. Just about every kid, takes this loan. Most of those use the money to buy a car. I know a young lady who did exactly that, and so did many of her friends. So kids with a starting pay of 45K also start life with a 35K. Buying a nice car in the military is especially silly as they cannot drive it while deployed and they are very likely to be deployed. At least, however, they are guaranteed a starting job with a nice starting pay, and upward potential. College kids who behave similarly might not have it as good. Will they even find work? Will the job have the ability to move up? How much security is in the job? One might say that this does not apply to engineers and such, but I am working with a fellow with a computer science degree who cannot find a job and has not worked in the past 6 months. This even though the market is super hot right now for computer engineers. So, in a word, be very careful what you borrow.",
"title": ""
},
{
"docid": "10098",
"text": "To a certain extent, small cap companies will in general follow the same trends as large cap companies. The extent of this cointegration depends on numerous factors, but a prime reason is the presence of systemic risk, i.e. the risk to the entire market. In simple terms, sthis is the risk that your portfolio will approach asymptotically as you increase its diversification, and it's why hedging is also important. That being said, small cap businesses will, in general, likely do worse than large cap stocks, for several reasons. This was/is certainly the case in the Great Recession. Small cap businesses have, on average, higher betas, which is a measure of a company's risk compared to the overall market. This means that small cap companies, on average outperform large cap companies during boom times, but it also means that they suffer more on average during bear times. The debate over whether or not the standard beta is still useful for small cap companies continues, however. Some economists feel that small cap companies are better measured against the Russell 2000 or similar indexes instead of the S&P 500. Small cap companies may face problems accessing or maintaining access to lines of credit. During the Great Recession, major lenders decreased their lending to small businesses, which might make it harder for them to weather the storm. On a related point, small businesses might not have as large an asset base to use as collateral for loans in bad times. One notable large cap company that used its asset base to their advantage was Ford, which gave banks partial ownership of its factories during hard times. This a) gave Ford a good amount of cash with which to continue their short-term operations, and b) gave the banks a vested interest in keeping Ford's lines of credit open. Ford struggled, but it never faced the financial problems of GM and Chrysler. Despite political rhetoric about Main Street vs. Wall Street, small businesses don't receive as much government aid in times of crisis as some large cap companies do. For example, the Small Business Lending Fund, a brilliant but poorly implemented idea in 2010, allocated less than $30 billion to small businesses. (The actual amount loaned was considerably less). Compare that to the amounts loaned out under TARP. Discussions about corporate lobbying power aside, small businesses aren't as crucial to the overall stability of the financial system Small businesses don't always have the manpower to keep up with changes in regulation. When the Dodd-Frank Act passed, large banks (as an example), could hire more staff to understand it and adapt to it relatively easily; small banks, however, don't always have the resources to invest in such efforts. There are other reasons, some of which are industry-specific, but these are some of the basic ones. If you want visual confirmation that small cap businesses follow a similar trend, here is a graph of the Russell 2000 and S&P 500 indexes: Here is a similar graph for the Russell 2000 and the Dow Jones Industrial Average. If you wanted to confirm this technically and control for the numerous complicated factors (overlap between indexes, systemic risk, seasonal adjustment, etc.), just ask and I'll try to run some numbers on it when I have a chance. Keep in mind, too, that looking at a pretty picture is no substitute for rigorous financial econometrics. A basic start would be to look at the correlation between the indexes, which I calculate as 0.9133 and 0.9526, respectively. As you can see, they're pretty close. Once again, however, the reality is more complicated technically, and a sufficiently detailed analysis is beyond my capabilities. Just a quick side note. These graphs show the logarithm of the values of the indexes, which is a common statistical nuance that is used when comparing time series with radically different magnitudes but similar trends. S&P500 and Russell 2000 data came from Yahoo! Finance, and the Dow Jones Industrial Average data came from Federal Reserve Economic Data (FRED) Per usual, I try to provide code whenever possible, if I used it. Here is the Stata code I used to generate the graphs above. This code assumes the presence of russell2000.csv and sp500.csv, downloaded from Yahoo! Finance, and DJIA.csv, downloaded from FRED, in the current directory. Fidelity published an article on the subject that you might find interesting, and Seeking Alpha has several pieces related to small-cap vs. large-cap returns that might be worth a read too.",
"title": ""
},
{
"docid": "287214",
"text": "This is how all corporations shift taxes to low income tax . Most large companies are actually hundreds of companies, with individual companies in each country they do business in. They use this type of transfer payment so most of the profits end up in countries with low income taxes. That is why you might as well lower the corporate rate. It will help employment, and end this kind of useless profit shifting. It's a world wide economy, and companies do what they need to do to keep taxes low no matter what.",
"title": ""
},
{
"docid": "178697",
"text": "\"This seems to depend on what kind of corporation you have set up. If you're set up as a sole proprietor, then the Solo 401k contributions, whether employee or employer, will be deducted from your gross income. Thus they don't reduce it. If you're set up as an S-Corp, then the employer contributions, similar to large employer contributions, will be deducted from wages, and won't show up in Box 1 on your W-2, so they would reduce your gross income. (Note, employee contributions also would go away from Box 1, but would still be in Box 3 and 5 for FICA/payroll tax purposes). This is nicely discussed in detail here. The IRS page that discusses this in more (harder to understand) detail is here. Separately, I think a discussion of \"\"Gross Income\"\" is merited, as it has a special definition for sole proprietorships. The IRS defines it in publication 501 as: Gross income. Gross income is all income you receive in the form of money, goods, property, and services that is not exempt from tax. If you are married and live with your spouse in a community property state, half of any income defined by state law as community income may be considered yours. For a list of community property states, see Community property states under Married Filing Separately, later. Self-employed persons. If you are self-employed in a business that provides services (where products are not a factor), your gross income from that business is the gross receipts. If you are self-employed in a business involving manufacturing, merchandising, or mining, your gross income from that business is the total sales minus the cost of goods sold. In either case, you must add any income from investments and from incidental or outside operations or sources. So I think that regardless of 401(k) contributions, your gross income is your gross receipts (if you're a contractor, it's probably the total listed on your 1099(s)).\"",
"title": ""
},
{
"docid": "335136",
"text": "\"Typically you diversify a portfolio to reduce risk. The S&P 500 is a collection of large-cap stocks; a diversified portfolio today probably contains a mix of large cap, small cap, bonds, international equity and cash. Right now, if you have a bond component, that part of your portfolio isn't performing as well. The idea of diversification is that you \"\"smooth out\"\" the ups and downs of the market and come out ahead in most situations. If you don't have a bond or cash component in your portfolio, you may have picked (or had someone pick for you) lousy funds. Without more detail, that's about all that can be said. EDIT: You provided more detail, so I want to add a little to my answer. Basically, you're in a fund that has high fees (1.58% annually) and performance that trails the mid-cap index. The S&P 500 is a large-cap index (large cap == large company), so a direct comparison is not necessarily meaningful. Since you seem to be new at this, I'd recommend starting out with the Vanguard Total Stock Market Index Fund (VTSMX) or ETF (VTI). This is a nice option because it represents the entire stock market and is cheap... it's a good way to get started without knowing alot. If your broker charges a transaction fee to purchase Vanguard funds and you don't want to change brokers or pay ETF commissions, look for or ask about transaction-fee free \"\"broad market\"\" indexes. The expense ratio should be below 0.50% per year and optimally under 0.20%. If you're not having luck finding investment options, swtich to a discount broker like TD Ameritrade, Schwab, ScottTrade or Fidelity (in no particular order)\"",
"title": ""
},
{
"docid": "391619",
"text": "It would be unusual but it is possible that the expenses could be very high compared to your income. The IRS in pub 529 explains the deduction. You can deduct only unreimbursed employee expenses that are: Paid or incurred during your tax year, For carrying on your trade or business of being an employee, and Ordinary and necessary. An expense is ordinary if it is common and accepted in your trade, business, or profession. An expense is necessary if it is appropriate and helpful to your business. An expense doesn't have to be required to be considered necessary. The next part lists examples. I have cut the list down to highlight ones that could be large. You may be able to deduct the following items as unreimbursed employee expenses. Damages paid to a former employer for breach of an employment contract. Job search expenses in your present occupation. Legal fees related to your job. Licenses and regulatory fees. Malpractice insurance premiums. Research expenses of a college professor. Rural mail carriers' vehicle expenses. Tools and supplies used in your work. Work clothes and uniforms if required and not suitable for everyday use. Work-related education. If the term of employment was only part of the year, one or more of the these could dwarf your income for the year. Before deducting something that large be sure you can document it. I believe the IRS computers would flag the return and I wouldn't be surprised if they ask for additional proof.",
"title": ""
},
{
"docid": "401753",
"text": "Actually, share holder value is is better maximised by borrowing, and paying dividends is fairly irrelevant but a natural phase on a mature and stable company. Company finance is generally a balance between borrowing, and money raised from shares. It should be self evident with a little thought that if not now, then in the future, a company should be able to create earnings in excess of the cost of borrowing, or it's not a very valuable company to invest in! In fact what's the point of borrowing if the cost of the interest is greater than whatever wealth is being generated? The important thing about this is that money raised from shares is more expensive than borrowing. If a company doesn't pay dividends, and its share price goes up because of the increasing value of the business, and in your example the company is not borrowing more because of this, then the proportion of the value of the company that is based on the borrowing goes down. So, this means a higher and higher proportion of the finance of a company is provided by the more expensive share holders than the less expensive borrowing, and thus the company is actually providing LESS value to share holders than it might. Of course, if a company doesn't pay a dividend AND borrows more, this is not true, but that's not the scenario in your question, and generally mature companies with mature earnings may as well pay dividends as they aren't on a massive expansion drive in the same way. Now, this relative expense of share holders and borrowing is MORE true for a mature company with stable earnings, as they are less of a risk and can borrow at more favourable rates, AND such a company is LIKELY to be expanding less rapidly than a small new innovative company, so for both these reasons returning money to share holders and borrowing (or maintaining existing lending facilities) maintains a relatively more efficient financing ratio. Of course all this means that in theory, a company should be more efficient if it has no share holders at all and borrows ALL of the money it needs. Yes. In practise though, lenders aren't so keen on that scenario, they would rather have shareholders sharing the risk, and lending a less than 100% proportion of the total of a companies finance means they are much more likely to get their money back if things go horribly wrong. To take a small start up company by comparison, lenders will be leary of lending at all, and will certainly impose high rates if they do, or ask for guarantors, or demand security (and security is only available if there is other investment besides the loan). So this is why a small start up is likely to be much more heavily or exclusively funded by share holders. Also the start up is likely not to pay a dividend, because for a start it's probably not making any profit, but even if it is and could pay a dividend, in this situation borrowing is unavailable or very expensive and this is a rapidly growing business that wants to keep its hands on all the cash it can to accelerate itself. Once it starts making money of course a start up is on its way to making the transition, it becomes able to borrow money at sensible rates, it becomes bigger and more valuable on the back of the borrowing. Another important point is that dividend income is more stable, at least for the mature companies with stable earnings of your scenario, and investors like stability. If all the income from a portfolio has to be generated by sales, what happens when there is a market crash? Suddenly the investor has to pay, where as with dividends, the company pays, at least for a while. If a company's earnings are hit by market conditions of course it's likely the dividend will eventually be cut, but short term volatility should be largely eliminated.",
"title": ""
},
{
"docid": "588607",
"text": "\"Rebalancing a portfolio helps you reduce risk, sell high, and buy low. I'll use international stocks and large cap US stocks. They both have ups and downs, and they don't always track with each other (international might be up while large cap US stocks are down and vice-versa) If you started with 50% international and 50% large cap stocks and 1 year later you have 75% international and 25% large cap stocks that means that international stocks are doing (relatively) well to large cap stocks. Comparing only those two categories, large cap stocks are \"\"on sale\"\" relative to international stocks. Now move so you have 50% in each category and you've realized some of the gains from your international investment (sell high) and added to your large cap stocks (buy low). The reason to rebalance is to lower risk. You are spreading your investments across multiple categories to manage risk. If you don't rebalance, you could end up with 95% in one category and 5% in another which means 95% of your portfolio is tied to the performance of a single asset category. I try to rebalance every 12 months and usually get it done by every 18 months. I like being a hands-off long term investor and this has proven often enough to beat the S&P500.\"",
"title": ""
},
{
"docid": "6479",
"text": "\"Thank you for some specific issues, from a former member. I see the company I work at making similar motions, hopefully I can start saying things like \"\"look, here is how that played out at GE\"\" Currently I'm trying to push the idea of RACI here so we'll see if we can't actually start an improvement. Edit: and not in response to you, but it's amazing how much push back I got from the generic \"\"blame the execs\"\" crowd. Large org are different from family businesses. It seems like people feel it's like running a coffee shop.\"",
"title": ""
},
{
"docid": "275312",
"text": "\"> No, what he's talking about are forums and other social sites that are too small to police all of the content their users post. He's saying that they are as guilty as the criminals you're speaking of. Still no. You start off with \"\"no\"\" and then admit he was not talking about all small businesses. Now you claim that all small tech businesses are going to get involved in sex trafficking. >I, however, am an expert on the subjec So are they publishers or common carriers? >He's saying that Google and Facebook and similar large corporations are legitimate, and all \"\"independent\"\" or small business competitors to them are criminals. You don't even seem to be competent in English no less a subject domain expert.\"",
"title": ""
},
{
"docid": "359718",
"text": "Most likely economics then. What I'm looking to gain is an understanding of how the market works so that I may take that knowledge and use it to make investments, buy stocks, or possibly start a business. I have a very large amount of time between my studies for my classes and I think it would be a waste to not learn these tools (to give you a reason for my interest in this).",
"title": ""
}
] |
PLAIN-1146
|
Exponent Inc.
|
[
{
"docid": "MED-1650",
"text": "Short abstract Campaigns to promote healthy eating are undermined by the ubiquity of processed, energy dense foods. A global strategy is now needed to tackle the rising prevalence of obesity",
"title": "Tobacco and obesity epidemics: not so different after all?"
},
{
"docid": "MED-2726",
"text": "The 2011 UN high-level meeting on non-communicable diseases (NCDs) called for multisectoral action including with the private sector and industry. However, through the sale and promotion of tobacco, alcohol, and ultra-processed food and drink (unhealthy commodities), transnational corporations are major drivers of global epidemics of NCDs. What role then should these industries have in NCD prevention and control? We emphasise the rise in sales of these unhealthy commodities in low-income and middle-income countries, and consider the common strategies that the transnational corporations use to undermine NCD prevention and control. We assess the effectiveness of self-regulation, public-private partnerships, and public regulation models of interaction with these industries and conclude that unhealthy commodity industries should have no role in the formation of national or international NCD policy. Despite the common reliance on industry self-regulation and public-private partnerships, there is no evidence of their effectiveness or safety. Public regulation and market intervention are the only evidence-based mechanisms to prevent harm caused by the unhealthy commodity industries. Copyright © 2013 Elsevier Ltd. All rights reserved.",
"title": "Profits and pandemics: prevention of harmful effects of tobacco, alcohol, and ultra-processed food and drink industries."
},
{
"docid": "MED-4602",
"text": "The strategy of \"manufacturing uncertainty\" has been used with great success by polluters and manufacturers of dangerous products to oppose public health and environmental regulation. This strategy entails questioning the validity of scientific evidence on which the regulation is based. While this approach is most identified with the tobacco industry, it has been used by producers of asbestos, benzene, beryllium, chromium, diesel exhaust, lead, plastics, and other hazardous products to avoid environmental and occupational health regulation. It is also central to the debate on global warming. The approach is now so common that it is unusual for the science not to be challenged by an industry facing regulation. Manufacturing uncertainty has become a business in itself; numerous technical consulting firms provide a service often called \"product defense\" or \"litigation support.\" As these names imply, the usual objective of these activities is not to generate knowledge to protect public health but to protect a corporation whose products are alleged to have toxic properties. Evidence in the scientific literature of the funding effect--the close correlation between the results of a study desired by a study's funder and the reported results of that study--suggests that the financial interest of a study's sponsors should be taken into account when considering the study's findings. Similarly, the interpretation of data by scientists with financial conflicts should be seen in this light. Manufacturing uncertainty is antithetical to the public health principle that decisions be made using the best evidence currently available.",
"title": "Manufactured uncertainty: protecting public health in the age of contested science and product defense."
},
{
"docid": "MED-2221",
"text": "Context: In 1954 the tobacco industry paid to publish the “Frank Statement to Cigarette Smokers” in hundreds of U.S. newspapers. It stated that the public's health was the industry's concern above all others and promised a variety of good-faith changes. What followed were decades of deceit and actions that cost millions of lives. In the hope that the food history will be written differently, this article both highlights important lessons that can be learned from the tobacco experience and recommends actions for the food industry. Methods: A review and analysis of empirical and historical evidence pertaining to tobacco and food industry practices, messages, and strategies to influence public opinion, legislation and regulation, litigation, and the conduct of science. Findings: The tobacco industry had a playbook, a script, that emphasized personal responsibility, paying scientists who delivered research that instilled doubt, criticizing the “junk” science that found harms associated with smoking, making self-regulatory pledges, lobbying with massive resources to stifle government action, introducing “safer” products, and simultaneously manipulating and denying both the addictive nature of their products and their marketing to children. The script of the food industry is both similar to and different from the tobacco industry script. Conclusions: Food is obviously different from tobacco, and the food industry differs from tobacco companies in important ways, but there also are significant similarities in the actions that these industries have taken in response to concern that their products cause harm. Because obesity is now a major global problem, the world cannot afford a repeat of the tobacco history, in which industry talks about the moral high ground but does not occupy it.",
"title": "The Perils of Ignoring History: Big Tobacco Played Dirty and Millions Died. How Similar Is Big Food?"
},
{
"docid": "MED-1651",
"text": "Background Limited information is available regarding the impact of candy consumption on health. The purpose of this study was to investigate associations between typical frequency of candy consumption and body weight status and select cardiovascular risk factors among adults in the United States. Methods Using data collected in the 2003–2006 National Health and Nutrition Examination Surveys (NHANES), adults were categorized as infrequent (≤ 3 eating occasions [EO]/month), moderate (> 3 EO/month and ≤ 3.5 EO/week), or frequent (> 3.5 EO/week) candy consumers based on the combined frequency of chocolate and other candy consumption over the previous 12 months. Weight and adiposity status were analyzed using logistic regression models, and blood pressure, lipids, and insulin sensitivity were analyzed using linear regression models. Models were adjusted for age, sex and race/ethnicity, and also for additional covariates with potential associations with the outcomes. Appropriate statistical weights were used to yield results generalizable to the US population. Results Frequency of candy consumption was not associated with the risk of obesity, overweight/obesity, elevated waist circumference, elevated skinfold thickness, blood pressure, low density lipoprotein (LDL) or high density lipoprotein (HDL) cholesterol, triglycerides, or insulin resistance. Increased frequency of candy consumption was associated with higher energy intakes and higher energy adjusted intakes of carbohydrates, total sugars and added sugars, total fat, saturated fatty acids and monounsaturated fatty acids (p < 0.05), and lower adjusted intakes of protein and cholesterol (p < 0.001). Conclusions Increased frequency of candy consumption among adults in the United States was not associated with objective measures of adiposity or select cardiovascular risk factors, despite associated dietary differences. Given the cross-sectional study design, however, it cannot be concluded that candy consumption does not cause obesity or untoward levels of cardiovascular risk markers. The lack of an association between frequency of candy consumption and cardiovascular risk factors could be due to reduced intake of candy among the overweight due to dieting or a health professional’s recommendations. Additionally, it is important to note that the analysis was based on frequency of candy consumption and not amount of candy consumed. Longitudinal studies are needed to confirm the lack of associations between frequency of candy consumption and cardiovascular risk factors.",
"title": "Body weight status and cardiovascular risk factors in adults by frequency of candy consumption"
}
] |
[
{
"docid": "MED-1705",
"text": "Despite an archive of over 73,000 research papers published in the last two decades on the subject of Alzheimer's disease (AD), little clinical progress has been made relative to how people get sporadic AD and what can be done to help them avoid it. This review spotlights strategic steps that could be a turning point in the dramatic lowering of Alzheimer prevalence. The main strategy includes application of four pillars of prevention: 1) early identification of AD vascular risk factors; 2) early detection of AD vascular risk factors; 3) early intervention of AD vascular risk factors based on evidence-based medical decisions; 4) patient follow-up to assess and modify interventions as needed. Tandem to these four pillars of prevention, a proactive lifestyle consisting of a healthy diet coupled to physical and mental activity should be applied as part of any therapeutic intervention. We are persuaded by mounting and compelling evidence that AD is a multifactorial disorder kindled by vascular risk factors that generate chronic brain hypoperfusion (CBH) during advanced aging. A pathobiological cascade of biochemical events in the presence of CBH that leads to oxidative stress and neurodegeneration appears to involve multiple biofactors including micronutrients, trace metals, lipids, and pro-oxidants, as reviewed in this special issue of BioFactors. Modulation of these biofactors may help prevent or control incipient AD. © 2012 International Union of Biochemistry and Molecular Biology, Inc. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.",
"title": "A turning point for Alzheimer's disease?"
},
{
"docid": "MED-1138",
"text": "PURPOSE: We compared the effect of 3 animal protein sources on urinary stone risk. MATERIALS AND METHODS: A total of 15 healthy subjects completed a 3-phase randomized, crossover metabolic study. During each 1-week phase subjects consumed a standard metabolic diet containing beef, chicken or fish. Serum chemistry and 24-hour urine samples collected at the end of each phase were compared using mixed model repeated measures analysis. RESULTS: Serum and urinary uric acid were increased for each phase. Beef was associated with lower serum uric acid than chicken or fish (6.5 vs 7.0 and 7.3 mg/dl, respectively, each p <0.05). Fish was associated with higher urinary uric acid than beef or chicken (741 vs 638 and 641 mg per day, p = 0.003 and 0.04, respectively). No significant difference among phases was noted in urinary pH, sulfate, calcium, citrate, oxalate or sodium. Mean saturation index for calcium oxalate was highest for beef (2.48), although the difference attained significance only compared to chicken (1.67, p = 0.02) but not to fish (1.79, p = 0.08). CONCLUSIONS: Consuming animal protein is associated with increased serum and urine uric acid in healthy individuals. The higher purine content of fish compared to beef or chicken is reflected in higher 24-hour urinary uric acid. However, as reflected in the saturation index, the stone forming propensity is marginally higher for beef compared to fish or chicken. Stone formers should be advised to limit the intake of all animal proteins, including fish. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.",
"title": "Animal protein and the risk of kidney stones: a comparative metabolic study of animal protein sources."
},
{
"docid": "MED-335",
"text": "OBJECTIVE: Meat and milk products are important sources of dietary phosphorus (P) and protein. The use of P additives is common both in processed cheese and meat products. Measurement of in vitro digestible phosphorus (DP) content of foods may reflect absorbability of P. The objective of this study was to measure both total phosphorus (TP) and DP contents of selected meat and milk products and to compare amounts of TP and DP and the proportion of DP to TP among different foods. METHODS: TP and DP contents of 21 meat and milk products were measured by inductively coupled plasma optical emission spectrometry (ICP-OES). In DP analysis, samples were digested enzymatically, in principle, in the same way as in the alimentary canal before the analyses. The most popular national brands of meat and milk products were chosen for analysis. RESULTS: The highest TP and DP contents were found in processed and hard cheeses; the lowest, in milk and cottage cheese. TP and DP contents in sausages and cold cuts were lower than those in cheeses. Chicken, pork, beef, and rainbow trout contained similar amounts of TP, but slightly more variation was found in their DP contents. CONCLUSIONS: Foods containing P additives have a high content of DP. Our study confirms that cottage cheese and unenhanced meats are better choices than processed or hard cheeses, sausages, and cold cuts for chronic kidney disease patients, based on their lower P-to-protein ratios and sodium contents. The results support previous findings of better P absorbability in foods of animal origin than in, for example, legumes. Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.",
"title": "Differences among total and in vitro digestible phosphorus content of meat and milk products."
},
{
"docid": "MED-1148",
"text": "PURPOSE: The etiology of hypospadias is poorly understood. Exposure to pesticides has been considered a risk factor, although findings are inconsistent. Diet constitutes a significant exposure route for pesticides, and pesticide residues are more frequently reported in conventional than organic food products. We examined the association between organic dietary choice during pregnancy and presence of hypospadias in the offspring. MATERIALS AND METHODS: Mothers of 306 boys operated on for hypospadias were frequency matched for geography and child birth year to 306 mothers of healthy boys in a case-control study. Telephone interviews were conducted regarding demographic and lifestyle factors, including intake and organic choice of selected food items (milk, dairy products, egg, fruit, vegetables and meat). Logistic regression models were constructed for dietary variables, and odds ratios were calculated controlling for maternal age, body mass index and alcohol consumption. RESULTS: Overall organic choice of food items during pregnancy was not associated with hypospadias in the offspring. However, frequent current consumption of high fat dairy products (milk, butter) while rarely or never choosing the organic alternative to these products during pregnancy was associated with increased odds of hypospadias (adjusted OR 2.18, 95% CI 1.09-4.36). CONCLUSIONS: This large case-control study of boys operated on for hypospadias suggests an association between hypospadias in the offspring and the mother not choosing the organic alternative, and having a high current intake of nonorganic butter and cheese. This finding could be due to chemical contamination of high fat dairy products. However, general lifestyle and health behavior related to choosing organic alternatives may also explain the finding. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.",
"title": "Association between organic dietary choice during pregnancy and hypospadias in offspring: a study of mothers of 306 boys operated on for hypospadias."
},
{
"docid": "MED-334",
"text": "OBJECTIVE: Among plant foods, grain products, legumes, and seeds are important sources of phosphorus (P). Current data on P content and absorbability of P from these foods are lacking. Measurement of in vitro digestible P (DP) content of foods may reflect absorbability of P. The objective of this study was to measure both total phosphorus (TP) and DP contents of selected foods and to compare the amounts of TP and DP and the proportion of DP to TP among different foods. METHODS: TP and DP content of 21 foods and drinks of plant origin were measured by inductively coupled plasma optical emission spectrometry. In DP analysis, samples were digested enzymatically in principle in the same way as in the alimentary canal before P analyses. The most popular national brands were chosen for analysis. RESULTS: The highest amount of TP (667 mg/100 g) was found in sesame seeds with hull, which also had the lowest percentage of DP (6%) to TP. Instead, in cola drinks and beer, the percentage of DP to TP was 87 to 100% (13 to 22 mg/100 g). In cereal products, the highest TP content (216 mg/100 g) and DP proportion (100%) were present in industrial muffins, which contain sodium phosphate as a leavening agent. Legumes contained an average DP content of 83 mg/100 g (38% of TP). CONCLUSION: Absorbability of P may differ substantially among different plant foods. Despite high TP content, legumes may be a relatively poor P source. In foods containing phosphate additives, the proportion of DP is high, which supports previous conclusions of the effective absorbability of P from P additives. Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.",
"title": "Differences among total and in vitro digestible phosphorus content of plant foods and beverages."
},
{
"docid": "MED-5242",
"text": "PURPOSE: Epidemiological studies in women have revealed an association between caffeine intake and urinary incontinence, although evidence among men is limited. Therefore, we evaluated the association between caffeine intake and urinary incontinence in United States men. MATERIALS AND METHODS: Data were used from male NHANES (National Health and Nutrition Examination Surveys) 2005-2006 and 2007-2008 participants. Urinary incontinence was defined using a standard questionnaire with Incontinence Severity Index scores 3 or greater categorized as moderate to severe. Structured dietary recall was used to determine caffeine consumption (mg per day), water intake (gm per day) and total dietary moisture (gm per day). Stepwise multivariable logistic regression models were used to assess the association between caffeine intake at or above the 75th and 90th percentiles and moderate to severe urinary incontinence, controlling for potential confounders, urinary incontinence risk factors and prostate conditions in men age 40 years or older. RESULTS: Of the 5,297 men 3,960 (75%) were 20 years old or older with complete data. Among these men the prevalence of any urinary incontinence was 12.9% and moderate to severe urinary incontinence was 4.4%. Mean caffeine intake was 169 mg per day. Caffeine intake at the upper 75th percentile (234 mg or more daily) and 90th percentile (392 mg or more per day) was significantly associated with having moderate to severe urinary incontinence (1.72, 95% 1.18-2.49 and 2.08, 95% 1.15-3.77, respectively). In addition, after adjusting for prostate conditions, the effect size for the association between caffeine intake and moderate to severe urinary incontinence remained. CONCLUSIONS: Caffeine consumption equivalent to approximately 2 cups of coffee daily (250 mg) is significantly associated with moderate to severe urinary incontinence in United States men. Our findings support the further study of caffeine modification in men with urinary incontinence. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.",
"title": "Caffeine intake and its association with urinary incontinence in United States men: results from National Health and Nutrition Examination Surveys ..."
},
{
"docid": "MED-3092",
"text": "BACKGROUND: Restriction of dietary phosphorus is a major aspect of patient care in those with renal disease. Restriction of dietary phosphorus is necessary to control for phosphate balance during both conservative therapy and dialysis treatment. The extra amount of phosphorus which is consumed as a result of phosphate-containing food additives is a real challenge for patients with renal disease and for dieticians because it represents a \"hidden\" phosphate load. The objective of this study was to measure phosphorus content in foods, common protein sources in particular, and comprised both those which included a listing of phosphate additives and those which did not. METHODS: Determinations of dry matter, nitrogen, total and soluble phosphate ions were carried out in 60 samples of foods, namely cooked ham, roast breast turkey, and roast breast chicken, of which, 30 were with declared phosphate additives and the other 30 similar items were without additives. RESULTS: Total phosphorus (290 ± 40 mg/100 g vs. 185 ± 23 mg/100 g, P < .001) and soluble phosphorus (164 ± 25 mg/100 g vs. 100 ± 19 mg/100 g, P < .001) content were higher in products containing additives than in foods without additives. No difference was detected between the 2 groups regarding dry matter (27.2 ± 2.0 g/100 g vs. 26.7 ± 1.9 g/100 g) or total nitrogen (3.15 ± 0.40 g/100 g vs. 3.19 ± 0.40 g/100 g). Consequently, phosphorus intake per gram of protein was much greater in the foods containing phosphorus additives (15.0 ± 3.1 mg/g vs. 9.3 ± 0.7 mg/g, P < .001). CONCLUSIONS: Our results show that those foods which contain phosphate additives have a phosphorus content nearly 70% higher than the samples which did not contain additives. This creates a special concern because this extra amount of phosphorus is almost completely absorbed by the intestinal tract. These hidden phosphates worsen phosphate balance control and increase the need for phosphate binders and related costs. Information and educational programs are essential to make patients with renal disease aware of the existence of foods with phosphate additives. Moreover, these facts highlight the need for national and international authorities to devote more attention to food labels which should clearly report the amount of natural or added phosphorus. Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.",
"title": "Extra-phosphate load from food additives in commonly eaten foods: a real and insidious danger for renal patients."
},
{
"docid": "MED-2298",
"text": "Exercise is a fundamental component of good health. The American College of Sports Medicine and \"Exercise is Medicine\" recommend treating exercise as a vital sign, and assessing and prescribing physical activity at every medical visit. Meeting the recommended goals of physical activity results in a significant reduction in all-cause mortality. Physicians can improve health by prescribing exercise. Copyright © 2013 Elsevier Inc. All rights reserved.",
"title": "A guide to exercise prescription."
},
{
"docid": "MED-3109",
"text": "The aryl hydrocarbon receptor (AhR) is responsible for the toxic effects of environmental pollutants such as dioxin, but little is known about its normal physiological functions. Li et al. (2011) now show that specific dietary compounds present in cruciferous vegetables act through the AhR to promote intestinal immune function, revealing AhR as a critical link between diet and immunity. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "You AhR what you eat: linking diet and immunity."
},
{
"docid": "MED-4685",
"text": "The incidence of neonatal vitamin B12 (cobalamin) deficiency because of maternal deficiency was determined by surveying state newborn screening programs. Thirty-two infants with nutritional vitamin B12 deficiency were identified (0.88/100,000 newborns). Pregnant women should be assessed for their risk of inadequate intake/malabsorption of vitamin B12. Copyright (c) 2010 Mosby, Inc. All rights reserved.",
"title": "Maternal and neonatal vitamin B12 deficiency detected through expanded newborn screening--United States, 2003-2007."
},
{
"docid": "MED-1753",
"text": "Given the history of GMO conflict and debate, the GM animal future is dependent on the response of the regulatory landscape and its associated range of interest groups at national, regional and international levels. Focusing on the EU and the USA, this article examines the likely form of that multi-level response, the increased role of cultural values, the contribution of new and existing interest groups and the consequent implications for the commercialization of both green and red GM animal biotechnology. Copyright © 2012. Published by Elsevier Inc.",
"title": "The current state of GMO governance: are we ready for GM animals?"
},
{
"docid": "MED-4502",
"text": "Kidney stones are increasingly common in wealthy industrialized countries. The most frequent form (80%) is idiopathic calcium stone disease. Eating habits and lifestyle have a direct effect on the lithogenic urinary risk factors and the pathogenesis of this condition. A diet characterized by a high intake of fluids, fruits, and vegetables; a low consumption of salt and protein; and a balanced intake of calcium, fats, and carbohydrates constitutes an efficacious approach to the prevention and treatment of this illness. A correct body weight, regular exercise, and a reduction in stressful life events are also useful preventive actions. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "Lifestyle recommendations to reduce the risk of kidney stones."
},
{
"docid": "MED-1585",
"text": "As the incidence of twin gestation increases, it is important to consider the maternal risks associated with carrying multiples. Compared with singleton gestation, there are increased risks to the mother during the antepartum, intrapartum, and postpartum periods. Certain pregnancy complications are more likely to occur during a twin gestation, including preeclampsia and other hypertensive disorders, antepartum hospitalization for preterm labor or abnormal bleeding, nutritional deficiencies, cesarean delivery, and postpartum hemorrhage. Women carrying twins may benefit from early education regarding these issues, close maternal monitoring as well as physical therapy sessions, and nutrition counseling during their pregnancies. Copyright © 2012 Elsevier Inc. All rights reserved.",
"title": "Effects of twin gestation on maternal morbidity."
},
{
"docid": "MED-2157",
"text": "Patients with cirrhosis are at greatest risk for development of hepatocellular carcinoma (HCC) and should undergo semiannual surveillance using ultrasound, with or without alpha fetoprotein. Patients with positive surveillance testing should undergo contrast-enhanced MRI or 4-phase CT for diagnostic evaluation. There are therapeutic options for most patients with any tumor stage; however, treatment decisions must be individualized after accounting for degree of liver dysfunction and patient performance status. A multidisciplinary approach to care is recommended for optimal communication and treatment delivery. The aim of this review is to provide an up-to-date summary of the diagnosis and management of HCC. Copyright © 2014 Elsevier Inc. All rights reserved.",
"title": "Hepatocellular carcinoma and other liver lesions."
},
{
"docid": "MED-1217",
"text": "Clostridium difficile has been recognized as an important human pathogen for several decades, but its importance as an agent of animal disease was established only recently. The number of reports on C. difficile in food is rising, but the findings vary among studies. In North America, the prevalence of contamination in retail meat and meat products ranges from 4.6% to 50%. In European countries, the percentage of C. difficile positive samples is much lower (0-3%). This chapter summarizes current data on association of C. difficile with different foods and the difficulties associated with isolation of the organism, and discusses the potential of C. difficile as a food-transmitted pathogen. Copyright © 2010 Elsevier Inc. All rights reserved.",
"title": "Clostridium difficile: its potential as a source of foodborne disease."
},
{
"docid": "MED-2240",
"text": "Curcumin interacts with a large number of extra- and intracellular targets in a biphasic dose-dependent manner. It controls inflammation, oxidative stress, cell survival, cell secretion, homeostasis, and proliferation. Its mechanisms of action are generally directed toward cells that exhibit disordered physiology or blatant mutation-based abnormal states. Optimizing preventative or therapeutic applications require delivering appropriate quantities of curcumin to lesioned cellular targets. Since diseased conditions anatomically are located from topical to systemic sites, efficient application of curcumin requires specific lesion-oriented delivery methods, representatives of which are here reviewed. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.",
"title": "Curcumin (diferuloylmethane) delivery methods: a review."
},
{
"docid": "MED-2347",
"text": "Urticaria affects nearly 25% of the population at some time in their lives. In a subset of children, urticaria will develop into a chronic condition that can greatly affect quality of life. Although numerous causes and triggers are proposed for chronic urticaria (CU) in children, ranging from infections, allergens, and medications to physical factors and autoimmune disease, the exact etiology is not always identifiable. Accordingly, a large subset of cases are designated \"chronic idiopathic urticaria.\" Because of the clinical complexities of CU, as well as the confusing literature on this topic, we have developed a conceptual framework based on the cumulative evidence to assist with the categorization, clinical evaluation, and treatment of CU in children. © 2011 Wiley Periodicals, Inc.",
"title": "Evidence-based evaluation and management of chronic urticaria in children."
},
{
"docid": "MED-2991",
"text": "PURPOSE: To determine the contents of chicken nuggets from 2 national food chains. BACKGROUND: Chicken nuggets have become a major component of the American diet. We sought to determine the current composition of this highly processed food. METHODS: Randomly selected nuggets from 2 different national fast food chains were fixed in formalin, sectioned and stained for microscopic analysis. RESULTS: Striated muscle (chicken meat) was not the predominate component in either nugget. Fat was present in equal or greater quantities along with epithelium, bone, nerve, and connective tissue. CONCLUSION: Chicken nuggets are mostly fat, and their name is a misnomer. Copyright © 2013 Elsevier Inc. All rights reserved.",
"title": "The autopsy of chicken nuggets reads \"chicken little\"."
},
{
"docid": "MED-1033",
"text": "OBJECTIVE: The bowel obsession syndrome (BOS) is a psychosomatic disorder which often remains at the intersection of somatic and psychological domains without being adequately diagnosed and treated. CASE REPORT: A 32-year-old man with chronic constipation presented with restricted diet, compulsions on evacuation, social isolation and depressed mood, thus satisfying the diagnosis of BOS. Cognitive behavioral therapy led to complete remission of symptoms, and results were maintained after 1 year of follow-up. CONCLUSION: Although BOS is not frequently diagnosed, it is probably more prevalent than thought. Clinicians should be aware of its existence in order to assess, diagnose and properly treat it. Copyright © 2013 Elsevier Inc. All rights reserved.",
"title": "\"Bowel obsession syndrome\" in a patient with chronic constipation."
},
{
"docid": "MED-3429",
"text": "Sexual problems are diffuse in both genders. Although epidemiologic evidence seems to support a role for lifestyle factors in erectile dysfunction, limited data are available suggesting the treatment of underlying risk factors may improve erectile dysfunction. The results are sparse regarding associations between lifestyle factors and female sexual dysfunction, and conclusions regarding influence of healthy behaviors on female sexual dysfunction cannot be made before more studies have been performed. Beyond the specific effects on sexual dysfunctions in men and women, adoption of these measures promotes a healthier life and increased well-being, which may help reduce the burden of sexual dysfunction. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "Lifestyle/dietary recommendations for erectile dysfunction and female sexual dysfunction."
},
{
"docid": "MED-3441",
"text": "As modern lifestyles and new feeding habits settle in the world, noncommunicable diseases (NCDs) have evolved to be major causes of disability in developing as well as developed countries. As a concomitant effect, there is a growing interest in natural, healthy food and an increasing awareness of risk factors and determinants of disease. This chapter describes some nutritional facts about seaweeds, which have been used as food since ancient times in China, Japan, Egypt, and India and comments on the potential utilization of marine algae as functional foods. This concept and the description of metabolic syndrome are used as a basis to comprehension of seaweeds against two dreadful illnesses of our times: high blood pressure and cancer. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "Marine edible algae as disease preventers."
},
{
"docid": "MED-3667",
"text": "The potential genotoxicity of lavender essential oil and its major components, linalool, and linalyl acetate, was evaluated in vitro by the micronucleus test on peripheral human lymphocytes. In the range of non-toxic concentrations (0.5-100 μg/ml), linalyl acetate increased the frequency of micronuclei significantly and in concentration-dependent manner; lavender oil did so only at the highest concentration tested, whereas linalool was devoid of genotoxicity. None of the tested substances led to an increase in nucleoplasmic bridges or nuclear buds frequency. These findings suggest that the mutagenic activity of lavender oil can be related to the presence of linalyl acetate, which seems to have a profile of an aneugenic agent. Copyright © 2010 Wiley-Liss, Inc.",
"title": "Genotoxicity of lavender oil, linalyl acetate, and linalool on human lymphocytes in vitro."
},
{
"docid": "MED-3708",
"text": "Asthma is a phenotypically heterogeneous disorder of multifactorial origins that affects 300 million people suffering from asthma and more than 250,000 asthma-related deaths each year. Although treatment for asthma has improved, its prevalence continues to increase, particularly in low and middle income countries, or in some ethnic groups in which prevalence was previously low. Observed spatio-temporal variations in the increased prevalence of asthma depend on exposure to environmental factors. Recently, several arguments are also in favor of the involvement of host susceptibility and stress in the observed increase of asthma prevalence. Further investigations are warranted to better understand mechanisms underlying asthma increase or stagnation. Copyright © 2012 Elsevier Inc. All rights reserved.",
"title": "Is the asthma epidemic still ascending?"
},
{
"docid": "MED-4575",
"text": "Vitamin D deficiency is the most common nutritional deficiency and likely the most common medical condition in the world. The major cause of vitamin D deficiency has been the lack of appreciation that the body requires 5- to 10-fold higher intakes than is currently recommended by health agencies. There is now overwhelming and compelling scientific and epidemiologic data suggesting that the human body requires a blood level of 25(OH)D above 30 ng/mL for maximum health. To increase the blood level to the minimum 30 ng/mL requires the ingestion of at least 1000 IU of vitamin D per day for adults. In general, there is no downside to increasing either a child's or adult's vitamin D intake. Copyright 2010 Elsevier Inc. All rights reserved.",
"title": "Vitamin D: extraskeletal health."
},
{
"docid": "MED-4873",
"text": "The use of over-the-counter supplements is commonplace in today's health conscious society. We present an unusual case of intrahepatic cholestasis caused by vitamin A intoxication. The patient consumed one Herbalife shake with two multivitamin tablets of the same brand for 12 years. When calculated this equated to more than the recommended daily allowance for vitamin A consumption. Deranged liver function tests were consistent with a cholestatic process. Liver biopsy was obtained and revealed features pathognomonic of vitamin A toxicity, without the usual fibrosis. When the supplements were ceased, his jaundice and alkaline phosphatase completely normalized. This case highlights the importance of health care providers documenting non-prescribed dietary supplements and considering them in the etiology of cholestatic liver disease. Copyright 2009 Elsevier Inc. All rights reserved.",
"title": "Hypervitaminosis A inducing intra-hepatic cholestasis--a rare case report."
},
{
"docid": "MED-2803",
"text": "Osteoarthritis is a condition caused in part by injury, loss of cartilage structure and function, and an imbalance in inflammatory and anti-inflammatory pathways. It primarily affects the articular cartilage and subchondral bone of synovial joints and results in joint failure, leading to pain upon weight bearing including walking and standing. There is no cure for osteoarthritis, as it is very difficult to restore the cartilage once it is destroyed. The goals of treatment are to relieve pain, maintain or improve joint mobility, increase the strength of the joints and minimize the disabling effects of the disease. Recent studies have shown an association between dietary polyphenols and the prevention of osteoarthritis-related musculoskeletal inflammation. This review discusses the effects of commonly consumed polyphenols, including curcumin, epigallocatechin gallate and green tea extract, resveratrol, nobiletin and citrus fruits, pomegranate, as well as genistein and soy protein, on osteoarthritis with an emphasis on molecular antiosteoarthritic mechanisms. Copyright © 2012 Elsevier Inc. All rights reserved.",
"title": "Dietary polyphenols and mechanisms of osteoarthritis."
},
{
"docid": "MED-1054",
"text": "For a long time non communicable diseases (NCDs) were discussed as burden of the developed world. Recent alarming data show a reverse trend and a dramatic increase of NCDs in the developing world, in particular in highly populated transition countries. This is true for the main mortality triggering diseases such as CVD, cancer or diabetes. Almost 4 out of 5 NCD based deaths happen in low- and middle income countries. This development is multi-factorial and is based on some main trends such as globalization, supermarket growth, rapid urbanization and increasingly sedentary lifestyles. The latter leads to overweight or obesity, which again promotes NCDs similar as high blood pressure, high cholesterol and elevated blood glucose. A high quality diet including functional food or functional ingredients, accompanied by physical activity and a non-smoking policy, is one of the most promising factors in primary and secondary prevention of NCDs. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "A global view on the development of non communicable diseases."
},
{
"docid": "MED-1686",
"text": "Beneficial effects of consumption of fruit and vegetables on the cardiovascular system have been reported. Fruit and vegetable components affect the cardiovascular system in both antioxidant and nonantioxidant ways. The mechanisms of their actions are, however, still not well understood. The compounds present in fruits and vegetables may function individually or in concert to protect lipoproteins and vascular cells from oxidation or by other mechanisms such as reducing plasma lipid levels, high blood pressure, and platelet hyperactivity. Emerging data indicate that kiwifruit is beneficial in the prevention of cardiovascular disease, as consumption of two or three fruit per day for 28 days or more lowers platelet hyperactivity, plasma lipids, and blood pressure in human volunteers. These studies suggest that kiwifruit may provide a new dietary means as part of a preventive or therapeutic strategy to favorably modify cardiovascular risk factors. The relevance of lowering the cardiovascular risk factors by kiwifruit in human health is discussed. Copyright © 2013 Elsevier Inc. All rights reserved.",
"title": "Cardioprotective properties of kiwifruit."
},
{
"docid": "MED-1998",
"text": "The growing epidemic of type 2 diabetes is one of the leading causes of premature morbidity and mortality worldwide, mainly due to the micro- and macrovascular complications associated with the disease. A growing body of evidence suggests that although the risk of developing complications is greater with glucose levels beyond the established threshold for diagnosis--increasing in parallel with rising hyperglycemia-individuals with glucose levels in the prediabetic range are already at increased risk. Early intervention, ideally as soon as abnormalities in glucose homeostasis are detected, is of great importance to minimize the burden of the disease. However, as the early stages of the disease are asymptomatic, diagnosing prediabetes and early overt type 2 diabetes is challenging. The aim of this article is to discuss these challenges, the benefits of early intervention--with emphasis on the prevention trials showing that progression to type 2 diabetes can be delayed by addressing prediabetes--and the existing evidence-based guidelines that have been drawn to optimize the standards of care at the prediabetes and overt type 2 diabetes stages. Copyright © 2013. Published by Elsevier Inc.",
"title": "The early treatment of type 2 diabetes."
},
{
"docid": "MED-2772",
"text": "Prostate cancer has become the most common cancer among men in the United States. Although milk consumption is considered to be a risk factor in some epidemiological studies, the results are inconsistent. A meta-analysis method was conducted to estimate the combined odds ratio (OR) between milk consumption and prostate cancer from case-control studies published between 1984 and 2003 using commercial software (comprehensive meta-analysis). The combined OR was 1.68 (95% confidence interval = 1.34-2.12) in the 11 published case-control studies. The combined OR varied little by study stratification. Additionally, we evaluated the possible risk factors in milk for prostate cancer. In conclusion, we found a positive association between milk consumption and prostate cancer. The underlying mechanisms, including fat, calcium, hormones, and other factors, should be investigated further. Copyright 2004 Lawrence Erlbaum Associates, Inc.",
"title": "Milk consumption is a risk factor for prostate cancer: meta-analysis of case-control studies."
}
] |
PLAIN-1447
|
Johns Hopkins University
|
[
{
"docid": "MED-2245",
"text": "Curcumin (diferuloylmethane) is being considered as a potential chemopreventive agent in humans. In vitro it inhibits transcription by NF-kappaB, and the activity of lipoxygenase or cyclooxygenase enzymes, which facilitate tumor progression. In vivo it is protective in rodent models of chemical carcinogenesis. Curcumin contains an alpha,beta-unsaturated ketone, a reactive chemical substituent that is responsible for its repression of NF-kappaB. In compounds other than curcumin this same electrophilic moiety is associated with inactivation of the tumor suppressor, p53. Here we report that curcumin behaves analogously to these compounds. It disrupts the conformation of the p53 protein required for its serine phosphorylation, its binding to DNA, its transactivation of p53-responsive genes and p53-mediated cell cycle arrest.",
"title": "Curcumin impairs tumor suppressor p53 function in colon cancer cells."
},
{
"docid": "MED-2246",
"text": "Curcuma spp. extracts, particularly the dietary polyphenol curcumin, prevent colon cancer in rodents. In view of the sparse information on the pharmacodynamics and pharmacokinetics of curcumin in humans, a dose-escalation pilot study of a novel standardized Curcuma extract in proprietary capsule form was performed at doses between 440 and 2200 mg/day, containing 36-180 mg of curcumin. Fifteen patients with advanced colorectal cancer refractory to standard chemotherapies received Curcuma extract daily for up to 4 months. Activity of glutathione S-transferase and levels of a DNA adduct (M(1)G) formed by malondialdehyde, a product of lipid peroxidation and prostaglandin biosynthesis, were measured in patients' blood cells. Oral Curcuma extract was well tolerated, and dose-limiting toxicity was not observed. Neither curcumin nor its metabolites were detected in blood or urine, but curcumin was recovered from feces. Curcumin sulfate was identified in the feces of one patient. Ingestion of 440 mg of Curcuma extract for 29 days was accompanied by a 59% decrease in lymphocytic glutathione S-transferase activity. At higher dose levels, this effect was not observed. Leukocytic M(1)G levels were constant within each patient and unaffected by treatment. Radiologically stable disease was demonstrated in five patients for 2-4 months of treatment. The results suggest that (a) Curcuma extract can be administered safely to patients at doses of up to 2.2 g daily, equivalent to 180 mg of curcumin; (b) curcumin has low oral bioavailability in humans and may undergo intestinal metabolism; and (c) larger clinical trials of Curcuma extract are merited.",
"title": "Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer."
},
{
"docid": "MED-2247",
"text": "The genetic alterations in colorectal cancer progression are determined by one of two separate and distinct underlying pathways of genomic instability. The first pathway, chromosomal instability, is characterized by allelic losses and aneuploidy. The second pathway, microsatellite instability, is characterized by an abundance of subtle DNA mutations and diploidy. Although the genes causing chromosomal instability remain unknown, microsatellite instability is caused by inactivation of a DNA mismatch repair gene (predominantly MLH1 or MSH2). Microsatellite instability is present in 15% of colorectal cancers, and is diagnosed by analysis of tumor DNA from paraffin blocks and by demonstration of loss of mismatch repair protein expression in cancers. In addition to the unique profile of genetic alterations, colorectal cancers with microsatellite instability have distinct pathologic features and improved survival. Finally, cancers from most patients with hereditary non-polyposis colorectal cancer (or Lynch syndrome) have microsatellite instability due to germline mutations in the DNA mismatch repair genes. Identification of the microsatellite instability pathway has enormous implications for the clinical investigation and management of colorectal cancer patients.",
"title": "Carcinogenesis in the GI tract: from morphology to genetics and back again."
},
{
"docid": "MED-2244",
"text": "BACKGROUND & AIMS: Familialadenomatous polyposis (FAP) is an autosomal-dominant disorder characterized by the development of hundreds of colorectal adenomas and eventual colorectal cancer. Regression of adenomas in this syndrome occurs with the administration of nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors, but these compounds can have considerable side effects. We evaluated the efficacy of the combination of diet-derived nonprescription supplements curcumin and quercetin to regress adenomas in patients with FAP. METHODS: Five FAP patients with prior colectomy (4 with retained rectum and 1 with an ileal anal pouch) received curcumin 480 mg and quercetin 20 mg orally 3 times a day. The number and size of polyps were assessed at baseline and after therapy. The Wilcoxon signed-rank test was used to determine differences in the number and size of polyps. Treatment side effects and medication compliance also were evaluated. RESULTS: All 5 patients had a decreased polyp number and size from baseline after a mean of 6 months of treatment with curcumin and quercetin. The mean percent decrease in the number and size of polyps from baseline was 60.4% (P < .05) and 50.9% (P < .05), respectively. Minimal adverse side effects and no laboratory abnormalities were noted. CONCLUSIONS: The combination of curcumin and quercetin appears to reduce the number and size of ileal and rectal adenomas in patients with FAP without appreciable toxicity. Randomized controlled trials are needed to validate these findings.",
"title": "Combination treatment with curcumin and quercetin of adenomas in familial adenomatous polyposis."
}
] |
[
{
"docid": "MED-1210",
"text": "Poor diet quality is thought to be a leading risk factor for years of life lost. We examined how scores on 4 commonly used diet quality indices-the Healthy Eating Index 2010 (HEI), the Alternative Healthy Eating Index 2010 (AHEI), the Alternate Mediterranean Diet (aMED), and the Dietary Approaches to Stop Hypertension (DASH)-are related to the risks of death from all causes, cardiovascular disease (CVD), and cancer among postmenopausal women. Our prospective cohort study included 63,805 participants in the Women's Health Initiative Observational Study (from 1993-2010) who completed a food frequency questionnaire at enrollment. Cox proportional hazards models were fit using person-years as the underlying time metric. We estimated multivariate hazard ratios and 95% confidence intervals for death associated with increasing quintiles of diet quality index scores. During 12.9 years of follow-up, 5,692 deaths occurred, including 1,483 from CVD and 2,384 from cancer. Across indices and after adjustment for multiple covariates, having better diet quality (as assessed by HEI, AHEI, aMED, and DASH scores) was associated with statistically significant 18%-26% lower all-cause and CVD mortality risk. Higher HEI, aMED, and DASH (but not AHEI) scores were associated with a statistically significant 20%-23% lower risk of cancer death. These results suggest that postmenopausal women consuming a diet in line with a priori diet quality indices have a lower risk of death from chronic disease. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.",
"title": "Comparing indices of diet quality with chronic disease mortality risk in postmenopausal women in the Women's Health Initiative Observational Study:..."
},
{
"docid": "MED-2094",
"text": "INTRODUCTION: An increasing number of people all around the world are turning to the nature by using the natural herbal products in both prophylaxes and treatment of different diseases. Green tea with active chemical ingredients posses diverse pharmacological properties that include anti-inflammatory, anticariogenic, antioxidant and antibacterial effects. AIMS: To assess the possible protective properties of green tea on oral health. METHODS: The researchers used the following measurements: Streptococcus mutans count in saliva and plaque, Salivary and plaque pH values, Gingival Bleeding Index (GBI). The above-mentioned measurements were applied to a sample consists of 25 subjects before and after rinsing with green tea for 5 min (short-term study). While, S. mutans count for saliva and plaque and GBI measurements, this experimental intervention study was carried out in the El-Azhar University dental clinic. RESULTS: The results of this study showed that there was a statistically significant difference among subjects pre- and post-rinsing with 2% green tea for 5 min concerning S. mutans count in saliva and plaque, salivary and plaque pH values and GBI. CONCLUSION: This study supports the effectiveness of local application of green tea as antibacterial and anticariogenic material as it decreases the acidity of the saliva and plaque, so it is a cost-effective caries prevention measures especially in developing countries. © 2009 John Wiley & Sons A/S.",
"title": "A pilot study of the role of green tea use on oral health."
},
{
"docid": "MED-2528",
"text": "OBJECTIVE: To describe changes in negative emotions among participants of a cholesterol-lowering study. DESIGN: Cohort study. Quantitative evaluation of changes in negative emotions in relation to diet and plasma cholesterol levels before and after a 5-year dietary intervention program aimed at reducing plasma cholesterol levels. SETTING: Community-dwelling families of the Family Heart Study, Portland, Oregon. PARTICIPANTS: One hundred forty-nine men and 156 women from 233 families (mean age, 37.7 years). MEASUREMENTS: Changes in negative emotions including depression and aggressive hostility as measured by the Hopkins Symptom Checklist (SCL-90). RESULTS: Improvement in overall emotional state was noted for the entire sample. Those who consumed a low-fat, high complex-carbohydrate diet at the end of the study showed significantly greater improvements in depression (P = 0.044; difference in improvement, 2.9 points) and aggressive hostility (P = 0.035; difference in improvement, 3.3 points) as well as a reduction in their plasma cholesterol levels (P = 0.024; difference in improvement, 2.7%) compared with those who ate a high-fat \"American diet.\" CONCLUSIONS: Participation in a cholesterol-lowering program may not be associated with a worsening in emotional state. To the contrary, improvements in diet appear to be associated with reductions in depression and aggressive hostility as well as with lowered plasma cholesterol levels.",
"title": "Improvements in hostility and depression in relation to dietary change and cholesterol lowering. The Family Heart Study."
},
{
"docid": "MED-3676",
"text": "In a previous clinical study, a probiotic formulation (PF) consisting of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 (PF) decreased stress-induced gastrointestinal discomfort. Emerging evidence of a role for gut microbiota on central nervous system functions therefore suggests that oral intake of probiotics may have beneficial consequences on mood and psychological distress. The aim of the present study was to investigate the anxiolytic-like activity of PF in rats, and its possible effects on anxiety, depression, stress and coping strategies in healthy human volunteers. In the preclinical study, rats were daily administered PF for 2 weeks and subsequently tested in the conditioned defensive burying test, a screening model for anti-anxiety agents. In the clinical trial, volunteers participated in a double-blind, placebo-controlled, randomised parallel group study with PF administered for 30 d and assessed with the Hopkins Symptom Checklist (HSCL-90), the Hospital Anxiety and Depression Scale (HADS), the Perceived Stress Scale, the Coping Checklist (CCL) and 24 h urinary free cortisol (UFC). Daily subchronic administration of PF significantly reduced anxiety-like behaviour in rats (P < 0·05) and alleviated psychological distress in volunteers, as measured particularly by the HSCL-90 scale (global severity index, P < 0·05; somatisation, P < 0·05; depression, P < 0·05; and anger-hostility, P < 0·05), the HADS (HADS global score, P < 0·05; and HADS-anxiety, P < 0·06), and by the CCL (problem solving, P < 0·05) and the UFC level (P < 0·05). L. helveticus R0052 and B. longum R0175 taken in combination display anxiolytic-like activity in rats and beneficial psychological effects in healthy human volunteers.",
"title": "Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and..."
},
{
"docid": "MED-743",
"text": "OBJECTIVE: To evaluate herbal medicines, other than St. John's wort, in the treatment of depression. DATA SOURCES/SEARCH METHODS: A computer-based search of Medline, Cinahl, AMED, ALT Health Watch, Psych Articles, Psych Info, Current Contents databases, Cochrane Controlled Trials Register, and Cochrane Database of Systematic Reviews, was performed. Researchers were contacted, and bibliographies of relevant papers and previous meta-analysis were hand searched for additional references. REVIEW METHODS: Trials were included in the review if they were prospective human trials assessing herbal medicines, other than St. John's wort, in the treatment of mild-to-moderate depression and utilized validated instruments to assess participant eligibility and clinical endpoints. RESULTS: Nine trials were identified that met all eligibility requirements. Three studies investigated saffron stigma, two investigated saffron petal, and one compared saffron stigma to the petal. Individual trials investigating lavender, Echium, and Rhodiola were also located. DISCUSSION: Results of the trials are discussed. Saffron stigma was found to be significantly more effective than placebo and equally as efficacious as fluoxetine and imipramine. Saffron petal was significantly more effective than placebo and was found to be equally efficacious compared to fluoxetine and saffron stigma. Lavender was found to be less effective than imipramine, but the combination of lavender and imipramine was significantly more effective than imipramine alone. When compared to placebo, Echium was found to significantly decrease depression scores at week 4, but not week 6. Rhodiola was also found to significantly improve depressive symptoms when compared to placebo. CONCLUSION: A number of herbal medicines show promise in the management of mild-to-moderate depression.",
"title": "Herbal medicines, other than St. John's Wort, in the treatment of depression: a systematic review."
},
{
"docid": "MED-1544",
"text": "This article outlines the advantages and disadvantages of universal and targeted intervention programs. Two advantages of universal programs are the absence of labeling and stigmatization, and the inclusion of the middle class which makes it more likely that the program will be well run. Two disadvantages are that they are unappealing to the public and politicians, and they may have their greatest effect on those at lowest risk. Targeted programs have the potential of addressing problems early on, and are potentially efficient if targeting can be done accurately. Disadvantages include difficulties around screening and the possibility of labeling and stigmatization. The argument is put forth that what is needed to reduce the immense burden of suffering from child and adolescent psychiatric disorders is the optimal mix of universal, targeted, and clinical programs carried out in the context of a civic community. There will always be trade-offs among these strategies, and the elements of the combination will change as knowledge accumulates.",
"title": "Selection of levels of prevention."
},
{
"docid": "MED-1359",
"text": "Previous meta-analyses investigating the effect of exercise on depression have included trials where the control condition has been categorized as placebo despite the fact that this particular placebo intervention (e.g., meditation, relaxation) has been recognized as having an antidepressant effect. Because meditation and mindfulness-based interventions are associated with depression reduction, it is impossible to separate the effect of the physical exercise from the meditation-related parts. The present study determined the efficacy of exercise in reducing symptoms of depression compared with no treatment, placebo conditions or usual care among clinically defined depressed adults. Of 89 retrieved studies, 15 passed the inclusion criteria of which 13 studies presented sufficient information for calculating effect sizes. The main result showed a significant large overall effect favoring exercise intervention. The effect size was even larger when only trials that had used no treatment or placebo conditions were analyzed. Nevertheless, effect size was reduced to a moderate level when only studies with high methodological quality were included in the analysis. Exercise may be recommended for people with mild and moderate depression who are willing, motivated, and physically healthy enough to engage in such a program. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.",
"title": "Physical exercise intervention in depressive disorders: meta-analysis and systematic review."
},
{
"docid": "MED-1740",
"text": "To assess human health risk from environmental chemicals, we have studied the effect on cell cycle regulation of the widely used glyphosate-containing pesticide Roundup. As a model system we have used sea urchin embryonic first divisions following fertilization, which are appropriate for the study of universal cell cycle regulation without interference with transcription. We show that 0.8% Roundup (containing 8 mM glyphosate) induces a delay in the kinetic of the first cell cleavage of sea urchin embryos. The delay is dependent on the concentration of Roundup. The delay in the cell cycle could be induced using increasing glyphosate concentrations (1-10 mM) in the presence of a subthreshold concentration of Roundup 0.2%, while glyphosate alone was ineffective, thus indicating synergy between glyphosate and Roundup formulation products. The effect of Roundup was not lethal and involved a delay in entry into M-phase of the cell cycle, as judged cytologically. Since CDK1/cyclin B regulates universally the M-phase of the cell cycle, we analyzed CDK1/cyclin B activation during the first division of early development. Roundup delayed the activation of CDK1/cyclin B in vivo. Roundup inhibited also the global protein synthetic rate without preventing the accumulation of cyclin B. In summary, Roundup affects cell cycle regulation by delaying activation of the CDK1/cyclin B complex, by synergic effect of glyphosate and formulation products. Considering the universality among species of the CDK1/cyclin B regulator, our results question the safety of glyphosate and Roundup on human health.",
"title": "Pesticide Roundup provokes cell division dysfunction at the level of CDK1/cyclin B activation."
},
{
"docid": "MED-5366",
"text": "CONTEXT: Adherence to the Mediterranean dietary pattern (MDP) is thought to reduce inflammatory, vascular, and metabolic processes that may be involved in the risk of clinical depression. OBJECTIVE: To assess the association between adherence to the MDP and the incidence of clinical depression. DESIGN: Prospective study that uses a validated 136-item food frequency questionnaire to assess adherence to the MDP. The MDP score positively weighted the consumption of vegetables, fruit and nuts, cereal, legumes, and fish; the monounsaturated- to saturated-fatty-acids ratio; and moderate alcohol consumption, whereas meat or meat products and whole-fat dairy were negatively weighted. SETTING: A dynamic cohort of university graduates (Seguimiento Universidad de Navarra/University of Navarra Follow-up [SUN] Project). PARTICIPANTS: A total of 10 094 initially healthy Spanish participants from the SUN Project participated in the study. Recruitment began on December 21, 1999, and is ongoing. MAIN OUTCOME MEASURE: Participants were classified as having incident depression if they were free of depression and antidepressant medication at baseline and reported a physician-made diagnosis of clinical depression and/or antidepressant medication use during follow-up. RESULTS: After a median follow-up of 4.4 years, 480 new cases of depression were identified. The multiple adjusted hazard ratios (95% confidence intervals) of depression for the 4 upper successive categories of adherence to the MDP (taking the category of lowest adherence as reference) were 0.74 (0.57-0.98), 0.66 (0.50-0.86), 0.49 (0.36-0.67), and 0.58 (0.44-0.77) (P for trend <.001). Inverse dose-response relationships were found for fruit and nuts, the monounsaturated- to saturated-fatty-acids ratio, and legumes. CONCLUSIONS: Our results suggest a potential protective role of the MDP with regard to the prevention of depressive disorders; additional longitudinal studies and trials are needed to confirm these findings.",
"title": "Association of the Mediterranean dietary pattern with the incidence of depression: the Seguimiento Universidad de Navarra/University of Navarra fol..."
},
{
"docid": "MED-4237",
"text": "OBJECTIVE: To evaluate the prevalence of benign prostatic hyperplasia (BPH) and prostatic cancer (CaP) in the mainland of China. METHODS: The incidence of BPH and CaP in urological hospital was investigated in 1997 in 26 provinces and 4 metropolises scattered over the mainland of China. The change of hospital incidences of BPH and CaP in the Institute of Urology, Beijing Medical University from 1951 to 1997 was also reviewed. RESULTS: The incidence of BPH and CaP in 1997 in 187 hospitals scattered over the mainland of China was 16.1% (15,459/95,749) and 1.5% (1389/95,749), respectively. The incidence of BPH and CaP in the Institute of Urology, Beijing University from 1951 to 1960 was 7.6% and 0.6%, respectively, while it was 18.5% and 3.4% from 1991 to 1997. CONCLUSION: The hospital incidence of BPH and CaP is rising rapidly in China, but CaP is still not a common disease in China.",
"title": "Epidemiological survey of benign prostatic hyperplasia and prostatic cancer in China."
},
{
"docid": "MED-1783",
"text": "Objective To assess the relationship between dietary antioxidant intake and semen quality in young healthy males Design Cross-sectional study Setting University and college campuses in the Rochester, New York, area Patients 189 university-aged men Interventions None Main Outcome Measures Semen volume, total sperm count, concentration, motility, total motile count, and morphology Results Progressive motility was 6.5 (95% CI 0.6, 12.3) percentage units higher among men in the highest quartile of β-carotene intake compared to men in the lowest quartile. Similar results were observed for lutein intake. Lycopene intake was positively related to sperm morphology. The adjusted percentages (95% CI) of morphologically normal sperm in increasing quartiles of lycopene intake were 8.0 (6.7, 9.3), 7.7 (6.4, 9.0), 9.2 (7.9, 10.5) and 9.7 (8.4, 11.0). There was a non-linear relationship between vitamin C intake and sperm concentration, with men in the second quartile of intake having, on average, the highest sperm concentrations and men in the top quartile of intake having the lowest concentrations. Conclusions In a population of healthy young men, carotenoid intake was associated with higher sperm motility and, in the case of lycopene, better sperm morphology. Our data suggest that dietary carotenoids may have a positive impact on semen quality.",
"title": "SEMEN QUALITY IN RELATION TO ANTIOXIDANT INTAKE IN A HEALTHY MALE POPULATION"
},
{
"docid": "MED-1388",
"text": "OBJECTIVE: The aim of this study was to assess the association between nut consumption and all-cause mortality after 5-y follow-up in a Spanish cohort. METHODS: The SUN (Seguimiento Universidad de Navarra, University of Navarra Follow-up) project is a prospective cohort study, formed by Spanish university graduates. Information is gathered by mailed questionnaires collected biennially. In all, 17 184 participants were followed for up to 5 y. Baseline nut consumption was collected by self-reported data, using a validated 136-item semi-quantitative food frequency questionnaire. Information on mortality was collected by permanent contact with the SUN participants and their families, postal authorities, and the National Death Index. The association between baseline nut consumption and all-cause mortality was assessed using Cox proportional hazards models to adjust for potential confounding. Baseline nut consumption was categorized in two ways. In a first analysis energy-adjusted quintiles of nut consumption (measured in g/d) were used. To adjust for total energy intake the residuals method was used. In a second analysis, participants were categorized into four groups according to pre-established categories of nut consumption (servings/d or servings/wk). Both analyses were adjusted for potential confounding factors. RESULTS: Participants who consumed nuts ≥2/wk had a 56% lower risk for all-cause mortality than those who never or almost never consumed nuts (adjusted hazard ratio, 0.44; 95% confidence intervals, 0.23-0.86). CONCLUSION: Nut consumption was significantly associated with a reduced risk for all-cause mortality after the first 5 y of follow-up in the SUN project. Copyright © 2014 Elsevier Inc. All rights reserved.",
"title": "Nut consumption and 5-y all-cause mortality in a Mediterranean cohort: the SUN project."
},
{
"docid": "MED-3395",
"text": "The available large prospective studies supporting an inverse association between better adherence to the Mediterranean diet and lower mortality have mainly included older adults. It is not clear whether this inverse association is also present among younger individuals at lower mortality risk. Our aim was to assess the association between adherence to the Mediterranean diet and total mortality in middle-aged adults from the Seguimiento Universidad de Navarra (SUN) Project. We followed 15,535 Spanish university graduates for a mean of 6.8 y. Their mean age was 38 ± 12 y, 59.6% were females, and all were initially free of cardiovascular disease, cancer, and diabetes. A validated FFQ was used to assess dietary habits. Adherence to the Mediterranean diet was categorized into 3 groups according to the Mediterranean Diet Score (low, 0-2 points; moderate, 3-5 points; and high, 6-9 points). The outcome variable was total mortality. Cox proportional hazards models were used to estimate HR and 95% CI. We adjusted the estimates for sex, age, years of university education, BMI, smoking, physical activity, television watching, history of depression and baseline hypertension, and hypercholesterolemia. We observed 125 deaths during 105,980 person-years of follow-up. The fully adjusted HR for moderate and high adherence were 0.58 (95% CI: 0.34, 0.99; P = 0.05) and 0.38 (95% CI: 0.21, 0.70; P = 0.002), respectively. For each 2-point increment in the Mediterranean Diet Score, the HR of death was 0.72 (95% CI: 0.58, 0.91; P = 0.006). Among highly educated, middle-aged adults, adherence to the traditional Mediterranean diet was associated with reduced risk of death.",
"title": "The Mediterranean diet is associated with a reduction in premature mortality among middle-aged adults."
},
{
"docid": "MED-1744",
"text": "Eighty percent of (commercial) genetically engineered seeds (GES) are designed only to resist herbicides. Letting farmers use more chemicals, they cut labor costs. But developing nations say GES cause food shortages, unemployment, resistant weeds, and extinction of native cultivars when \"volunteers\" drift nearby. While GES patents are reasonable, this paper argues many patent policies are not. The paper surveys GE technology, outlines John Locke's classic account of property rights, and argues that current patent policies must be revised to take account of Lockean ethical constraints. After answering a key objection, it provides concrete suggestions for implementing its ethical conclusions.",
"title": "Property rights and genetic engineering: developing nations at risk."
},
{
"docid": "MED-1947",
"text": "The present report, describes for the first time the clinical efficacy of curcumin, the active constituent of rhizomes of Curcuma longa, in the treatment of patients suffering from idiopathic inflammatory orbital pseudotumours. Curcumin was administered orally at a dose of 375 mg/3 times/day orally for a period of 6-22 months in eight patients. They were followed up for a period of 2 years at 3 monthly intervals. Five patients completed the study, out of which four recovered completely and in one patient the swelling regressed completely but some limitation of movement persisted. No side effect was noted in any patient and there was no recurrence. It is suggested that curcumin could be used as a safe and effective drug in the treatment of idiopathic inflammatory orbital pseudotumours. Copyright 2000 John Wiley & Sons, Ltd.",
"title": "Role of curcumin in idiopathic inflammatory orbital pseudotumours."
},
{
"docid": "MED-3918",
"text": "The study material consisted of five herbs: chamomile (flowers), mint (leaves), St John's wort (flowers and leaves), sage (leaves) and nettle (leaves), sourced from three producers. The calcium, magnesium, iron, zinc and copper contents were determined for both dried herb samples and prepared infusions, and the extraction rates were calculated. Mineral components were determined using atomic absorption spectrometry. Analysis showed that the contents of individual elements in herbs and infusions depended on the type of raw material, as well as on its origin. Moreover, it was found that iron penetrated the herbal infusions to the lowest degree (4.4-12.4%), while copper did so to the highest (26.7-50.7%). It is felt that in average consumption the herbal infusions are not important as calcium, magnesium, iron, zinc and copper sources in human nutrition.",
"title": "Herbal infusions as a source of calcium, magnesium, iron, zinc and copper in human nutrition."
},
{
"docid": "MED-4525",
"text": "The red sap obtained by slashing the bark of Croton urucurana Baill. (Euphorbiaceae), also known as dragon's blood, was screened for a possible antidiarrhoeal activity on castor oil-induced diarrhoea in rats, cholera toxin-induced intestinal secretion in mice and on small intestinal transit in mice. Dragon's blood at an oral dose of 600 mg/kg caused in marked inhibition of the diarrhoeal response following castor oil administration as well as the intestinal fluid accumulation promoted by cholera toxin. At a similar dose the red sap significantly inhibited the small intestinal transit which was, however, found to be independent of the opioid mechanism. These results suggest a potential usefulness of the red sap from Croton urucurana Baill. in the control of secretory diarrhoea associated pathologies. Copyright 2001 John Wiley & Sons, Ltd.",
"title": "Studies on the antidiarrhoeal effect of dragon's blood from Croton urucurana."
},
{
"docid": "MED-1125",
"text": "Genetic, molecular and biological studies indicate that rheumatoid arthritis (RA), a severe arthritic disorder affecting approximately 1% of the population in developed countries, is caused by an upper urinary tract infection by the microbe, Proteus mirabilis. Elevated levels of specific antibodies against Proteus bacteria have been reported from 16 different countries. The pathogenetic mechanism involves six stages triggered by cross-reactive autoantibodies evoked by Proteus infection. The causative amino acid sequences of Proteus namely, ESRRAL and IRRET, contain arginine doublets which can be acted upon by peptidyl arginine deiminase thereby explaining the early appearance of anti-citrullinated protein antibodies in patients with RA. Consequently, RA patients should be treated early with anti-Proteus antibiotics as well as biological agents to avoid irreversible joint damages. © 2013 APMIS. Published by John Wiley & Sons Ltd.",
"title": "Rheumatoid arthritis is caused by a Proteus urinary tract infection."
},
{
"docid": "MED-2031",
"text": "BACKGROUND: There has been increasing interest in the entity of Non-Celiac Gluten Sensitivity (NCGS) in recent years; however, it still remains a controversial topic and its pathogenesis is not well understood. Celiac Disease, in contrast, is a well-studied condition that has become increasingly recognized as a prevalent condition arising from a heightened immunological response to gluten. Wheat allergy is an IgE-mediated condition capable of causing a variety of gastrointestinal symptoms. However, the number of patients who have neither celiac disease nor wheat allergy, but appear to derive benefit from a gluten-free diet, is also increasing substantially. The use of the term NCGS as a way of describing this condition has become increasingly prevalent in recent years. PURPOSE: In this review, we will focus on gastrointestinal manifestations of NCGS and discuss the evidence for the condition and its putative pathogenesis. We will discuss areas of controversy and areas for potential future research. © 2013 John Wiley & Sons Ltd.",
"title": "Non-celiac gluten sensitivity: clinical relevance and recommendations for future research."
},
{
"docid": "MED-1444",
"text": "Coriander (Coriandrum sativum L.), a herbal plant, belonging to the family Apiceae, is valued for its culinary and medicinal uses. All parts of this herb are in use as flavoring agent and/or as traditional remedies for the treatment of different disorders in the folk medicine systems of different civilizations. The plant is a potential source of lipids (rich in petroselinic acid) and an essential oil (high in linalool) isolated from the seeds and the aerial parts. Due to the presence of a multitude of bioactives, a wide array of pharmacological activities have been ascribed to different parts of this herb, which include anti-microbial, anti-oxidant, anti-diabetic, anxiolytic, anti-epileptic, anti-depressant, anti-mutagenic, anti-inflammatory, anti-dyslipidemic, anti-hypertensive, neuro-protective and diuretic. Interestingly, coriander also possessed lead-detoxifying potential. This review focuses on the medicinal uses, detailed phytochemistry, and the biological activities of this valuable herb to explore its potential uses as a functional food for the nutraceutical industry. Copyright © 2012 John Wiley & Sons, Ltd.",
"title": "Coriander (Coriandrum sativum L.): a potential source of high-value components for functional foods and nutraceuticals--a review."
},
{
"docid": "MED-3552",
"text": "The study evaluated the protective effects of purple rice (Oryza sativa L.) bran extract (PRE) and its constituents, cyanidin and peonidin, against angiogenesis induced by vascular endothelial growth factor (VEGF). The effects of VEGF and PRE were examined by in vitro tube formation assays and following 14-day co-culture of human umbilical vein endothelial cells (HUVECs) and fibroblasts. The antiangiogenic mechanism of PRE was evaluated by VEGF-induced proliferation and migration of HUVECs and/or human retinal microvascular endothelial cells (HRMECs) and phosphorylation of extracellular signal-regulated kinase (ERK) and p38. The PRE significantly suppressed VEGF-induced tube formation, proliferation and migration in HUVECs and HRMECs as well as phosphorylation of ERK and p38. Cyanidin and peonidin also suppressed the proliferation and migration induced by VEGF. These findings indicate that PRE and anthocyanidins suppress VEGF-induced angiogenesis by inhibiting proliferation and migration and suggest that the inhibition of phosphorylated-ERK and -p38 may be involved in the underlying mechanism. Copyright © 2011 John Wiley & Sons, Ltd.",
"title": "Purple rice (Oryza sativa L.) extract and its constituents inhibit VEGF-induced angiogenesis."
},
{
"docid": "MED-3662",
"text": "Essential oils distilled from members of the genus Lavandula have been used both cosmetically and therapeutically for centuries with the most commonly used species being L. angustifolia, L. latifolia, L. stoechas and L. x intermedia. Although there is considerable anecdotal information about the biological activity of these oils much of this has not been substantiated by scientific or clinical evidence. Among the claims made for lavender oil are that is it antibacterial, antifungal, carminative (smooth muscle relaxing), sedative, antidepressive and effective for burns and insect bites. In this review we detail the current state of knowledge about the effect of lavender oils on psychological and physiological parameters and its use as an antimicrobial agent. Although the data are still inconclusive and often controversial, there does seem to be both scientific and clinical data that support the traditional uses of lavender. However, methodological and oil identification problems have severely hampered the evaluation of the therapeutic significance of much of the research on Lavandula spp. These issues need to be resolved before we have a true picture of the biological activities of lavender essential oil. Copyright 2002 John Wiley & Sons, Ltd.",
"title": "Biological activities of lavender essential oil."
},
{
"docid": "MED-5286",
"text": "Obesity remains a major public health challenge, and its prevalence is dramatically increasing. Diet and exercise are typically recommended to prevent and manage obesity; however, the results are often conflicting. Polyphenols, a class of phytochemicals that have been shown to reduce the risk factors for diabetes type II and cardiovascular diseases, are recently suggested as complementary agents in the management of obesity through several mechanisms such as decreasing fat absorption and/or fat synthesis. Dark chocolate, a high source of polyphenols, and flavanols in particular, has lately received attention for its possible role in modulating obesity because of its potential effect on fat and carbohydrate metabolism, as well as on satiety. This outcome was investigated in animal models of obesity, cell cultures and few human observational and clinical studies. The research undertaken to date has shown promising results, with the possible implication of cocoa/dark chocolate in the modulation of obesity and body weight through several mechanisms including decreasing the expression of genes involved in fatty acid synthesis, reducing the digestion and absorption of fats and carbohydrates and increasing satiety. Copyright © 2013 John Wiley & Sons, Ltd.",
"title": "Dark chocolate: an obesity paradox or a culprit for weight gain?"
},
{
"docid": "MED-3449",
"text": "Watercress (Cruciferae), an integral part of Mediterranean diets, is a nutritive food which is used in the treatment of several diseases. Oxidative DNA damage seems to play a crucial role in chronic, aging-related diseases and it is considered an important and probably carcinogenic factor. The aim of this work was to determine the impact of watercress extract on cell viability and its potential antigenotoxic properties against induced oxidative damage, using a comet assay and peripheral blood cells as an in vitro model. An aqueous extract of the leaves was prepared using a juice processor, centrifuged, filtered and preserved at -20 °C. Two concentrations of the aqueous extract (13.2 and 26.4 mg/mL) were assayed. No differences were found in cell viability between the control and treated groups at any time. Significant antigenotoxic effects were observed for both concentrations, expressed as the damage index (p = 0.005 at 30 min; p < 0.001 at 60 and 90 min), the percentage reductions in damage being similar between them (67.1-75.2% respectively). These results suggest that the consumption watercress in the diet is a powerful tool for improving health and the quality of life. Copyright © 2011 John Wiley & Sons, Ltd.",
"title": "Antigenotoxic activity of watercress extract in an in vitro mammalian system using comet assay."
},
{
"docid": "MED-3607",
"text": "The development of radioprotective agents has been the subject of intense research in view of their potential for use within a radiation environment, such as space exploration, radiotherapy and even nuclear war. However, no ideal, safe synthetic radioprotectors are available to date, so the search for alternative sources, including plants, has been on going for several decades. In Ayurveda, the traditional Indian system of medicine, several plants have been used to treat free radical-mediated ailments and, therefore, it is logical to expect that such plants may also render some protection against radiation damage. A systematic screening approach can provide leads to identifying potential new candidate drugs from plant sources, for mitigation of radiation injury. This article reviews some of the most promising plants, and their bioactive principles, that are widely used in traditional systems of medicine, and which have rendered significant radioprotection in both in vitro and in vivo model systems. Plants and their constituents with pharmacological activities that may be relevant to amelioration of radiation-mediated damage, including antiemetic, antiinflammatory, antioxidant, cell proliferative, wound healing and haemopoietic stimulatories are also discussed. Copyright (c) 2005 John Wiley & Sons, Ltd.",
"title": "Radioprotection by plant products: present status and future prospects."
},
{
"docid": "MED-1525",
"text": "Mentha spicata Labiatae, known as spearmint and Mentha piperita Labiatae, known as peppermint can be used for various kinds of illnesses in herbal medicine and flavoring in industry. M. spicata Labiatae grows on the Anamas plateau of Yenithornarbademli town of Isparta, located in southwest part of Turkey. In this town, clinicians thought that consumption of tea steeped with M. spicata or M. piperita caused a diminished libido. Because antiandrogenic effects of spearmint and peppermint were found previously in rats, it was decided to observe the effect of this herbal tea on the androgen levels in hirsute women.Twenty-one female hirsute patients, 12 with polycystic ovary syndrome and 9 with idiopathic hirsutism were included to the study. They were took a cup of herbal tea which was steeped with M. spicata for 5 days twice a day in the follicular phase of their menstrual cycles. After treatment with spearmint teas, there was a significant decrease in free testosterone and increase in luteinizing hormone, follicle-stimulating hormone and estradiol. There were no significant decreases in total testosterone or dehydroepiandrostenedione sulphate levels. Spearmint can be an alternative to antiandrogenic treatment for mild hirsutism. Further studies are needed to test the reliability of these results and the availability of spearmint as a drug for hirsutism. Copyright 2007 John Wiley & Sons, Ltd.",
"title": "Effect of spearmint (Mentha spicata Labiatae) teas on androgen levels in women with hirsutism."
},
{
"docid": "MED-2786",
"text": "Alzheimer's disease (AD) is the most common form of dementia. There is limited choice in modern therapeutics, and drugs available have limited success with multiple side effects in addition to high cost. Hence, newer and alternate treatment options are being explored for effective and safer therapeutic targets to address AD. Turmeric possesses multiple medicinal uses including treatment for AD. Curcuminoids, a mixture of curcumin, demethoxycurcumin, and bisdemethoxycurcumin, are vital constituents of turmeric. It is generally believed that curcumin is the most important constituent of the curcuminoid mixture that contributes to the pharmacological profile of parent curcuminoid mixture or turmeric. A careful literature study reveals that the other two constituents of the curcuminoid mixture also contribute significantly to the effectiveness of curcuminoids in AD. Therefore, it is emphasized in this review that each component of the curcuminoid mixture plays a distinct role in making curcuminoid mixture useful in AD, and hence, the curcuminoid mixture represents turmeric in its medicinal value better than curcumin alone. The progress in understanding the disease etiology demands a multiple-site-targeted therapy, and the curcuminoid mixture of all components, each with different merits, makes this mixture more promising in combating the challenging disease. Copyright © 2013 John Wiley & Sons, Ltd.",
"title": "Therapeutic potential of turmeric in Alzheimer's disease: curcumin or curcuminoids?"
},
{
"docid": "MED-1293",
"text": "In the domain of nutrition, exploring the diet-health linkages is major area of research. The outcomes of such interventions led to widespread acceptance of functional and nutraceutical foods; however, augmenting immunity is a major concern of dietary regimens. Indeed, the immune system is incredible arrangement of specific organs and cells that enabled humans to carry out defense against undesired responses. Its proper functionality is essential to maintain the body homeostasis. Array of plants and their components hold immunomodulating properties. Their possible inclusion in diets could explore new therapeutic avenues to enhanced immunity against diseases. The review intended to highlight the importance of garlic (Allium sativum), green tea (Camellia sinensis), ginger (Zingiber officinale), purple coneflower (Echinacea), black cumin (Nigella sativa), licorice (Glycyrrhiza glabra), Astragalus and St. John's wort (Hypericum perforatum) as natural immune boosters. These plants are bestowed with functional ingredients that may provide protection against various menaces. Modes of their actions include boosting and functioning of immune system, activation and suppression of immune specialized cells, interfering in several pathways that eventually led to improvement in immune responses and defense system. In addition, some of these plants carry free radical scavenging and anti-inflammatory activities that are helpful against cancer insurgence. Nevertheless, interaction between drugs and herbs/botanicals should be well investigated before recommended for their safe use, and such information must be disseminated to the allied stakeholders.",
"title": "Immunity: plants as effective mediators."
},
{
"docid": "MED-2344",
"text": "The increased consumption of fish and shellfish has resulted in more frequent reports of adverse reactions to seafood, emphasizing the need for more specific diagnosis and treatment of this condition and exploring reasons for the persistence of this allergy. This review discusses interesting and new findings in the area of fish and shellfish allergy. New allergens and important potential cross-reacting allergens have been identified within the fish family and between shellfish, arachnids, and insects. The diagnostic approach may require prick to-prick tests using crude extracts of both raw and cooked forms of seafood for screening seafood sensitization before a food challenge or where food challenge is not feasible. Allergen-specific immunotherapy can be important; mutated less allergenic seafood proteins have been developed for this purpose. The persistence of allergy because of seafood proteins' resistance after rigorous treatment like cooking and extreme pH is well documented. Additionally, IgE antibodies from individuals with persistent allergy may be directed against different epitopes than those in patients with transient allergy. For a topic as important as this one, new areas of technological developments will likely have a significant impact, to provide more accurate methods of diagnosing useful information to patients about the likely course of their seafood allergy over the course of their childhood and beyond. © 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.",
"title": "Fish and shellfish allergy in children: review of a persistent food allergy."
},
{
"docid": "MED-2822",
"text": "Curcumin is known to possess potent antiinflammatory and antiarthritic properties. This pilot clinical study evaluated the safety and effectiveness of curcumin alone, and in combination with diclofenac sodium in patients with active rheumatoid arthritis (RA). Forty-five patients diagnosed with RA were randomized into three groups with patients receiving curcumin (500 mg) and diclofenac sodium (50 mg) alone or their combination. The primary endpoints were reduction in Disease Activity Score (DAS) 28. The secondary endpoints included American College of Rheumatology (ACR) criteria for reduction in tenderness and swelling of joint scores. Patients in all three treatment groups showed statistically significant changes in their DAS scores. Interestingly, the curcumin group showed the highest percentage of improvement in overall DAS and ACR scores (ACR 20, 50 and 70) and these scores were significantly better than the patients in the diclofenac sodium group. More importantly, curcumin treatment was found to be safe and did not relate with any adverse events. Our study provides the first evidence for the safety and superiority of curcumin treatment in patients with active RA, and highlights the need for future large-scale trials to validate these findings in patients with RA and other arthritic conditions. Copyright © 2012 John Wiley & Sons, Ltd.",
"title": "A randomized, pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis."
}
] |
PLAIN-1883
|
plums
|
[
{
"docid": "MED-5083",
"text": "A predominantly plant-based diet reduces the risk for development of several chronic diseases. It is often assumed that antioxidants contribute to this protection, but results from intervention trials with single antioxidants administered as supplements quite consistently do not support any benefit. Because dietary plants contain several hundred different antioxidants, it would be useful to know the total concentration of electron-donating antioxidants (i.e., reductants) in individual items. Such data might be useful in the identification of the most beneficial dietary plants. We have assessed systematically total antioxidants in a variety of dietary plants used worldwide, including various fruits, berries, vegetables, cereals, nuts and pulses. When possible, we analyzed three or more samples of dietary plants from three different geographic regions in the world. Total antioxidants was assessed by the reduction of Fe(3+) to Fe(2+) (i.e., the FRAP assay), which occurred rapidly with all reductants with half-reaction reduction potentials above that of Fe(3+)/Fe(2+). The values, therefore, expressed the corresponding concentration of electron-donating antioxidants. Our results demonstrated that there is more than a 1000-fold difference among total antioxidants in various dietary plants. Plants that contain most antioxidants included members of several families, such as Rosaceae (dog rose, sour cherry, blackberry, strawberry, raspberry), Empetraceae (crowberry), Ericaceae (blueberry), Grossulariaceae (black currant), Juglandaceae (walnut), Asteraceae (sunflower seed), Punicaceae (pomegranate) and Zingiberaceae (ginger). In a Norwegian diet, fruits, berries and cereals contributed 43.6%, 27.1% and 11.7%, respectively, of the total intake of plant antioxidants. Vegetables contributed only 8.9%. The systematic analysis presented here will facilitate research into the nutritional role of the combined effect of antioxidants in dietary plants.",
"title": "A systematic screening of total antioxidants in dietary plants."
},
{
"docid": "MED-4715",
"text": "The present pilot study analyzed, for the first time, the in vivo effect of Medjool or Hallawi date consumption by healthy subjects on serum glucose, lipids, and oxidative stress. Total phenolics concentration in the Hallawi versus Medjool dates was greater by 20-31%. The major proportion of the soluble phenolics in both date varieties consisted of phenolic acids, mainly ferulic acid and coumaric acid derivatives, and also chlorogenic and caffeic acid derivatives. Unlike the Medjool dates, Hallawi dates contained a significant proportion of catechins as well. In addition, both varieties contained a quercetin derivative. Both date varieties possess antioxidative properties in vitro, but the ferric ion reducing antioxidant power of Hallawi versus Medjool dates was higher by 24%. Ten healthy subjects consumed, for a period of 4 weeks 100 g/day of either Medjool or Hallawi dates. The date consumption did not significantly affect the subjects' body mass index (BMI), their serum total cholesterol, or their cholesterol levels in the VLDL, LDL, or HDL fractions. Most important, fasting serum glucose and triacylglycerol levels were not increased after consumption of either date variety, and serum triacylglycerol levels even significantly (p < 0.05) decreased, by 8 or 15% after Medjool or Hallawi date consumption, respectively. Basal serum oxidative status was significantly (p < 0.01) decreased by 33%, as compared to the levels observed before consumption, after Hallawi (but not Medjool) date consumption. Similarly, the susceptibility of serum to AAPH-induced lipid peroxidation decreased by 12%, but only after Hallawi date consumption. In agreement with the above results, serum activity of the HDL-associated antioxidant enzyme paraoxonase 1 (PON1) significantly increased, by 8%, after Hallawi date consumption. It is concluded that date consumption (and mainly the Hallawi variety) by healthy subjects, despite their high sugar content, demonstrates beneficial effects on serum triacylglycerol and oxidative stress and does not worsen serum glucose and lipid/lipoprotein patterns, and thus can be considered an antiatherogenic nutrient .",
"title": "Effects of date ( Phoenix dactylifera L., Medjool or Hallawi Variety) consumption by healthy subjects on serum glucose and lipid levels and on seru..."
},
{
"docid": "MED-3907",
"text": "Background This study was designed to determine the glycemic indices of five commonly used varieties of dates in healthy subjects and their effects on postprandial glucose excursions in individuals with type 2 diabetes mellitus. Methods Composition analysis was carried out for five types of dates (Tamer stage). The weights of the flesh of the dates equivalent to 50 g of available carbohydrates were calculated. The study subjects were thirteen healthy volunteers with a mean (± SD) age of 40.2 ± 6.7 years and ten participants with type 2 diabetes mellitus (controlled on lifestyle measures and/or metformin) with a mean HbA1c (± SD) of 6.6 ± (0.7%) and a mean age (± SD) of 40.8 ± 5.7 years. Each subject was tested on eight separate days with 50 g of glucose (on 3 occasions) and 50 g equivalent of available carbohydrates from the 5 varieties of date (each on one occasion). Capillary glucose was measured in the healthy subjects at 0, 15, 30, 45, 60, 90 and 120 min and for the diabetics at 0, 30, 60, 90, 120, 150 and 180 min. The glycemic indices were determined as ratios of the incremental areas under the response curves for the dates compared to glucose. Statistical analyses were performed using the Mann-Whitney U test and repeated measures analysis of variance. Results Mean glycemic indices ± SEM of the dates for the healthy individuals were 54.0 ± 6.1, 53.5 ± 8.6, 46.3 ± 7.1, 49.1 ± 3.6 and 55.1 ± 7.7 for Fara'd, Lulu, Bo ma'an, Dabbas and Khalas, respectively. Corresponding values for those with type 2 diabetes were very similar (46.1 ± 6.2, 43.8 ± 7.7, 51.8 ± 6.9, 50.2 ± 3.9 and 53.0 ± 6.0). There were no statistically significant differences in the GIs between the control and the diabetic groups for the five types of dates, nor were there statistically significant differences among the dates' GIs (df = 4, F = 0.365, p = 0.83). Conclusion The results show low glycemic indices for the five types of dates included in the study and that their consumption by diabetic individuals does not result in significant postprandial glucose excursions. These findings point to the potential benefits of dates for diabetic subjects when used in a healthy balanced diet. Trial Registration Number ClinicalTrials.gov NCT01307904",
"title": "Glycemic indices of five varieties of dates in healthy and diabetic subjects"
},
{
"docid": "MED-3908",
"text": "BACKGROUND: Evidence suggests that consumption of apple or its bioactive components modulate lipid metabolism and reduce the production of proinflammatory molecules. However, there is a paucity of such research in human beings. OBJECTIVE: Women experience a lower rate of cardiovascular disease before menopause compared with men. However, after the onset of menopause, the risk of cardiovascular disease increases drastically due to ovarian hormone deficiency. Hence, we conducted a 1-year clinical trial to evaluate the effect of dried apple vs dried plum consumption in reducing cardiovascular disease risk factors in postmenopausal women. DESIGN: One-hundred sixty qualified postmenopausal women were recruited from the greater Tallahassee, FL, area during 2007-2009 and were randomly assigned to one of two groups: dried apple (75 g/day) or dried plum (comparative control). Fasting blood samples were collected at baseline, 3, 6, and 12 months to measure various parameters. Physical activity recall and 7-day dietary recall were also obtained. RESULTS: Neither of the dried fruit regimens significantly affected the participants' reported total energy intake throughout the study period. On the contrary, women who consumed dried apple lost 1.5 kg body weight by the end of the study, albeit not significantly different from the dried plum group. In terms of cholesterol, serum total cholesterol levels were significantly lower in the dried apple group compared with the dried plum group only at 6 months. Although dried plum consumption did not significantly reduce serum total cholesterol and low-density lipoprotein cholesterol levels, it lowered their levels numerically by 3.5% and 8%, respectively, at 12 months compared with baseline. This may explain the lack of significance observed between the groups. However, within the group, women who consumed dried apple had significantly lower serum levels of total cholesterol and low-density lipoprotein cholesterol by 9% and 16%, respectively, at 3 months compared with baseline. These serum values were further decreased to 13% and 24%, respectively, after 6 months but stayed constant thereafter. The within-group analysis also reported that daily apple consumption profoundly improved atherogenic risk ratios, whereas there were no significant changes in lipid profile or atherogenic risk ratios as a result of dried plum consumption. Both dried fruits were able to lower serum levels of lipid hydroperoxide and C-reactive protein. However, serum C-reactive protein levels were significantly lower in the dried plum group compared with the dried apple group at 3 months. CONCLUSIONS: There were no significant differences between the dried apple and dried plum groups in altering serum levels of atherogenic cholesterols except total cholesterol at 6 months. However, when within treatment group comparisons are made, consumption of 75 g dried apple (about two medium-sized apples) can significantly lower atherogenic cholesterol levels as early as 3 months. Furthermore, consumption of dried apple and dried plum are beneficial to human health in terms of anti-inflammatory and antioxidative properties. Copyright © 2012 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.",
"title": "Daily apple versus dried plum: impact on cardiovascular disease risk factors in postmenopausal women."
},
{
"docid": "MED-5084",
"text": "We assessed the contribution of culinary and medicinal herbs to the total intake of dietary antioxidants. Our results demonstrate that there is more than a 1000-fold difference among antioxidant concentrations of various herbs. Of the dried culinary herbs tested, oregano, sage, peppermint, garden thyme, lemon balm, clove, allspice and cinnamon as well as the Chinese medicinal herbs Cinnamomi cortex and Scutellariae radix all contained very high concentrations of antioxidants (i.e., >75 mmol/100 g). In a normal diet, intake of herbs may therefore contribute significantly to the total intake of plant antioxidants, and be an even better source of dietary antioxidants than many other food groups such as fruits, berries, cereals and vegetables. In addition, the herbal drug, Stronger Neo-Minophagen C, a glycyrrhizin preparation used as an intravenous injection for the treatment of chronic hepatitis, boosts total antioxidant intake. It is tempting to speculate that several of the effects due to these herbs are mediated by their antioxidant activities.",
"title": "Several culinary and medicinal herbs are important sources of dietary antioxidants."
},
{
"docid": "MED-3904",
"text": "BACKGROUND: Treatment of chronic constipation remains challenging with 50% of patients dissatisfied with current therapy. There is an unmet need for natural and safe alternatives. Dried plums (prunes) have been used traditionally for constipation but their efficacy is not known. Aim To assess and compare the effects of dried plums and psyllium in patients with chronic constipation. METHODS: Subjects were enrolled in an 8-week, single-blind, randomised cross-over study. Subjects received either dried plums (50 g b.d., fibre=6 gm/day) or psyllium (11 g b.d., fibre=6 gm/day) for 3 weeks each, in a crossover trial with a 1-week washout period. Subjects maintained a daily symptom and stool diary. Assessments included number of complete spontaneous bowel movements per week, global relief of constipation, stool consistency, straining, tolerability and taste. RESULTS: Forty constipated subjects (m/f=3/37, mean age=38 years) participated. The number of complete spontaneous bowel movements per week (primary outcome measure) and stool consistency scores improved significantly (P<0.05) with dried plums when compared to psyllium. Straining and global constipation symptoms did not differ significantly between treatments (P=N.S.). Dried plums and psyllium were rated as equally palatable and both were safe and well tolerated. CONCLUSION: Dried plums are safe, palatable and more effective than psyllium for the treatment of mild to moderate constipation, and should be considered as a first line therapy. © 2011 Blackwell Publishing Ltd.",
"title": "Randomised clinical trial: dried plums (prunes) vs. psyllium for constipation."
},
{
"docid": "MED-3906",
"text": "Date palm is one of the oldest trees cultivated by man. In the folk-lore, date fruits have been ascribed to have many medicinal properties when consumed either alone or in combination with other herbs. Although, fruit of the date palm served as the staple food for millions of people around the world for several centuries, studies on the health benefits are inadequate and hardly recognized as a healthy food by the health professionals and the public. In recent years, an explosion of interest in the numerous health benefits of dates had led to many in vitro and animal studies as well as the identification and quantification of various classes of phytochemicals. On the basis of available documentation in the literature on the nutritional and phytochemical composition, it is apparent that the date fruits are highly nutritious and may have several potential health benefits. Although dates are sugar-packed, many date varieties are low GI diet and refutes the dogma that dates are similar to candies and regular consumption would develop chronic diseases. More investigations in these areas would validate its beneficial effects, mechanisms of actions, and fully appreciate as a potential medicinal food for humans all around the world. Therefore, in this review we summarize the phytochemical composition, nutritional significance, and potential health benefits of date fruit consumption and discuss its great potential as a medicinal food for a number of diseases inflicting human beings.",
"title": "Date fruits (Phoenix dactylifera Linn): an emerging medicinal food."
},
{
"docid": "MED-5175",
"text": "OBJECTIVE: To investigate the relationships between nutritional and lifestyle factors and bowel movement frequency. DESIGN: Cross-sectional analysis using data from a prospective study. Mean numbers of bowel movements were calculated in relation to a range of factors. In addition, individuals were categorised according to frequency of bowel movements: fewer than 7 per week ('less than daily') versus 7 or more per week ('daily'), and odds ratios were calculated from logistic regression models. Results for each factor were adjusted for the other factors under consideration. SETTING: The European Prospective Investigation into Cancer and Nutrition, Oxford cohort (EPIC-Oxford), UK. PARTICIPANTS: In total, 20630 men and women aged 22-97 years at recruitment. Thirty per cent of the subjects were vegetarians or vegans. RESULTS: Women had fewer bowel movements on average than men, and were less likely to have daily bowel movements. Mean bowel movement frequency was higher in vegetarians (10.5 in men, 9.1 in women) and especially in vegans (11.6 in men, 10.5 in women) compared with participants who ate meat (9.5 in men, 8.2 in women). There were also significant positive associations between bowel movement frequency and body mass index (BMI), intakes of dietary fibre and non-alcoholic fluids, for both men and women. Vigorous exercise was positively associated with bowel movement frequency in women although results for men were less clear. Alcohol intake was positively associated with bowel movement frequency in men but not in women. CONCLUSION: Being vegetarian and especially vegan is strongly associated with a higher frequency of bowel movements. Moreover, having a high intake of dietary fibre and fluids and a high BMI are associated with an increase in frequency of bowel movements.",
"title": "Nutrition and lifestyle in relation to bowel movement frequency: a cross-sectional study of 20630 men and women in EPIC-Oxford."
},
{
"docid": "MED-3910",
"text": "Background Figs are a rich source of soluble fiber. We evaluated the effect of consuming dried California Mission figs on serum lipids in hyperlipidemic adults. Methods In a crossover trial men and women aged 30–75 years with elevated low-density lipoprotein cholesterol (100–189 mg/dl) were randomized to add dried California Mission figs (120 g/day) to their usual diet for 5 weeks or eat their usual diet for 5 weeks, then crossed over to the other condition for another 5 weeks. Six 24-hour dietary recalls were obtained. Results Low- and high-density lipoprotein cholesterol and triglyceride concentrations did not differ between usual and figs-added diets (Bonferroni-corrected p > 0.017), while total cholesterol tended to increase with fig consumption (p = 0.02). Total cholesterol increased in participants (n = 41) randomized to usual followed by figs-added diet (p = 0.01), but remained unchanged in subjects (n = 42) who started with figs-added followed by usual diet (p = 0.4). During the figs-added diet, soluble fiber intake was 12.6 ± 3.7 versus 8.2 ± 4.1 g/day in the usual diet (p < 0.0001). Sugar intake increased from 23.4 ± 6.5 to 32.2 ± 6.3% of kcal in the figs-added diet (p < 0.0001). Body weight did not change (p = 0.08). Conclusions Daily consumption of figs did not reduce low-density lipoprotein cholesterol. Triglyceride concentrations were not significantly changed despite an increase in sugar intake.",
"title": "Effect of Consumption of Dried California Mission Figs on Lipid Concentrations"
}
] |
[
{
"docid": "MED-2966",
"text": "OBJECTIVE: Determine 1) if consumption of a meal of different fruits or berries increases plasma hydrophilic (H-) or lipophilic (L-) antioxidant capacity (AOC) measured as Oxygen Radical Absorbance Capacity (ORAC(FL)); 2) if including macronutrients in the meal alters postprandial changes in AOC; and 3) if preliminary recommendations can be developed for antioxidant intake. METHODS: Changes in plasma AOC following consumption of a single meal of berries/fruits (blueberry, dried plum, dried plum juice, grape, cherry, kiwifruit and strawberry) were studied in 5 clinical trials with 6-10 subjects per experiment. In two studies with blueberry or grape, additional macronutrients (carbohydrate, fat, protein) were included in the control and treatment meals. Blood samples collected before and after the meal were analyzed for AOC. RESULTS: Consumption of dried plums or dried plum juice did not alter either the H- or L-AOC area under the curve (AUC). Consumption of blueberry in 2 studies and of mixed grape powder [12.5 (Study #1), 39.9 (Study #4) and 8.6 (Study #5) mmole Trolox Equivalents (TE) AOC, respectively] increased hydrophilic AOC AUC. L-AOC increased following a meal of blueberry containing 12.5 mmole TE AOC (Study #1). Consumption of 280 g of cherries (4.5 mmol TE AOC) increased plasma L-AOC but not H-AOC. The AOC in the control groups in which additional macronutrients (Studies #4 and #5) were added decreased from the postprandial baseline AOC measurement. CONCLUSION: We have demonstrated that consumption of certain berries and fruits such as blueberries, mixed grape and kiwifruit, was associated with increased plasma AOC in the postprandial state and consumption of an energy source of macronutrients containing no antioxidants was associated with a decline in plasma AOC. However, without further long term clinical studies, one cannot necessarily translate increased plasma AOC into a potential decreased risk of chronic degenerative disease. Preliminary estimates of antioxidant needs based upon energy intake were developed. Consumption of high antioxidant foods with each meal is recommended in order to prevent periods of postprandial oxidative stress.",
"title": "Plasma antioxidant capacity changes following a meal as a measure of the ability of a food to alter in vivo antioxidant status."
},
{
"docid": "MED-4413",
"text": "Estimation of total antioxidant intake is the first step to investigate the protective effects of antioxidants on oxidative stress-mediated disease. The present study was designed to develop an algorithm to estimate total antioxidant capacity (TAC) of the US diet. TAC of individual antioxidants and 50 popular antioxidant-rich food items in the US diet were determined by 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) assay and the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. Theoretical TAC of foods was calculated as the sum of individual antioxidant capacities of compounds. The top 10 TAC food items in the US diet according to standard serving size were blueberry > plum > green tea > strawberry > green tea (decaffeinated) > red wine > grape juice > black tea > cherry > grape. Major contributors to TAC were the total phenolic content (r = 0.952, P < 0.001) and flavonoid content (r = 0.827, P < 0.001) of 50 foods. Theoretical TAC was positively correlated to experimental TAC of 50 foods determined by the ABTS assay (r = 0.833, P < 0.001) and the DPPH assay (r = 0.696, P < 0.001), and to TAC from the USDA database for the oxygen radical absorbance capacity (r = 0.484, P = 0.001, n = 44). The TAC database of the US diet has been established and validated. In future studies, TAC of the US diet can be linked to biomarkers of chronic disease.",
"title": "Development and validation of an algorithm to establish a total antioxidant capacity database of the US diet."
},
{
"docid": "MED-2663",
"text": "Today, tens of millions of elderly individuals worldwide suffer from dementia. While the pathogenesis of dementia is complex and incompletely understood, it may be, at least to a certain extent, the consequence of systemic vascular pathology. The metabolic syndrome and its individual components induce a proinflammatory state that damages blood vessels. This condition of chronic inflammation may damage the vasculature of the brain or be directly neurotoxic. Associations have been established between the metabolic syndrome, its constituents and dementia. A relationship has also been observed between certain dietary factors, such as constituents of the 'Mediterranean diet', and the metabolic syndrome; similar associations have been noted between these dietary factors and dementia. Fruit juices and extracts are under investigation as treatments for cognitive impairment. Blueberry, strawberry, blackberry, grape and plum juices or extracts have been successfully tested in cognitively impaired rodents. Published trials of the benefits of grape and blueberry juice in the treatment of small numbers of cognitively impaired persons have recently appeared. The benefits of fruit products are thought to be a result of its polyphenol content. A grape polyphenol found in grapes, resveratrol, now being studied in humans, and one in grapes and blueberries, pterostilbene, have been found to improve cognition in rodents. In the design of future human trials, one ought to consider the poor bioavailability of these products, the possible need to initiate the experimental therapy long before the onset of symptoms, and currently limited knowledge about the appropriate form (e.g. juice, powder or individual polyphenol) of treatment.",
"title": "A berry thought-provoking idea: the potential role of plant polyphenols in the treatment of age-related cognitive disorders."
},
{
"docid": "MED-1795",
"text": "Objective To determine whether individual fruits are differentially associated with risk of type 2 diabetes. Design Prospective longitudinal cohort study. Setting Health professionals in the United States. Participants 66 105 women from the Nurses’ Health Study (1984-2008), 85 104 women from the Nurses’ Health Study II (1991-2009), and 36 173 men from the Health Professionals Follow-up Study (1986-2008) who were free of major chronic diseases at baseline in these studies. Main outcome measure Incident cases of type 2 diabetes, identified through self report and confirmed by supplementary questionnaires. Results During 3 464 641 person years of follow-up, 12 198 participants developed type 2 diabetes. After adjustment for personal, lifestyle, and dietary risk factors of diabetes, the pooled hazard ratio of type 2 diabetes for every three servings/week of total whole fruit consumption was 0.98 (95% confidence interval 0.96 to 0.99). With mutual adjustment of individual fruits, the pooled hazard ratios of type 2 diabetes for every three servings/week were 0.74 (0.66 to 0.83) for blueberries, 0.88 (0.83 to 0.93) for grapes and raisins, 0.89 (0.79 to 1.01) for prunes, 0.93 (0.90 to 0.96) for apples and pears, 0.95 (0.91 to 0.98) for bananas, 0.95 (0.91 to 0.99) for grapefruit, 0.97 (0.92 to 1.02) for peaches, plums, and apricots, 0.99 (0.95 to 1.03) for oranges, 1.03 (0.96 to 1.10) for strawberries, and 1.10 (1.02 to 1.18) for cantaloupe. The pooled hazard ratio for the same increment in fruit juice consumption was 1.08 (1.05 to 1.11). The associations with risk of type 2 diabetes differed significantly among individual fruits (P<0.001 in all cohorts). Conclusion Our findings suggest the presence of heterogeneity in the associations between individual fruit consumption and risk of type 2 diabetes. Greater consumption of specific whole fruits, particularly blueberries, grapes, and apples, is significantly associated with a lower risk of type 2 diabetes, whereas greater consumption of fruit juice is associated with a higher risk.",
"title": "Fruit consumption and risk of type 2 diabetes: results from three prospective longitudinal cohort studies"
},
{
"docid": "MED-1846",
"text": "The effects of the chemical composition of fruit juices and fruit on the absorption of iron from a rice (Oryza sativa) meal were measured in 234 parous Indian women, using the erythrocyte utilization of radioactive Fe method. The corrected geometric mean Fe absorptions with different juices varied between 0.040 and 0.129, with the variation correlating closely with the ascorbic acid contents of the juices (rs 0.838, P less than 0.01). Ascorbic acid was not the only organic acid responsible for the promoting effects of citrus fruit juices on Fe absorption. Fe absorption from laboratory 'orange juice' (100 ml water, 33 mg ascorbic acid and 750 mg citric acid) was significantly better than that from 100 ml water and 33 mg ascorbic acid alone (0.097 and 0.059 respectively), while Fe absorption from 100 ml orange juice (28 mg ascorbic acid) was better than that from 100 ml water containing the same amount of ascorbic acid (0.139 and 0.098 respectively). Finally, Fe absorption from laboratory 'lemon juice' (100 ml orange juice and 4 g citric acid) was significantly better than that from 100 ml orange juice (0.226 and 0.166 respectively). The corrected geometric mean Fe absorption from the rice meal was 0.025. Several fruits had little or no effect on Fe absorption from the meal (0.013-0.024). These included grape (Vitis vinifera), peach (Prunus persica), apple (Malus sylvestris) and avocado pear (Persea americana). Fruit with a mild to moderate enhancing effect on Fe absorption (0.031-0.088) included strawberry (Fragaria sp.) (uncorrected values), plum (Prunus domestica), rhubarb (Rheum rhaponticum), banana (Musa cavendishii), mango (Mangifera indica), pear (Pyrus communis), cantaloup (Cucumis melo) and pineapple (Ananas comosus) (uncorrected values). Guava (Psidium guajava) and pawpaw (Carica papaya) markedly increased Fe absorption (0.126-0.293). There was a close correlation between Fe absorption and the ascorbic acid content of the fruits tested (rs 0.738, P less than 0.0001). There was also a weaker but significant correlation with the citric acid content (rs 0.55, P less than 0.03). Although this may have reflected a direct effect of citric acid on Fe absorption, it should be noted that fruits containing citric acid also contained ascorbic acid (rs 0.70, P less than 0.002).(ABSTRACT TRUNCATED AT 400 WORDS)",
"title": "The effects of fruit juices and fruits on the absorption of iron from a rice meal."
},
{
"docid": "MED-3945",
"text": "The pomegranate fruit ( Punica granatum ) has become an international high-value crop for the production of commercial pomegranate juice (PJ). The perceived consumer value of PJ is due in large part to its potential health benefits based on a significant body of medical research conducted with authentic PJ. To establish criteria for authenticating PJ, a new International Multidimensional Authenticity Specifications (IMAS) algorithm was developed through consideration of existing databases and comprehensive chemical characterization of 45 commercial juice samples from 23 different manufacturers in the United States. In addition to analysis of commercial juice samples obtained in the United States, data from other analyses of pomegranate juice and fruits including samples from Iran, Turkey, Azerbaijan, Syria, India, and China were considered in developing this protocol. There is universal agreement that the presence of a highly constant group of six anthocyanins together with punicalagins characterizes polyphenols in PJ. At a total sugar concentration of 16 degrees Brix, PJ contains characteristic sugars including mannitol at >0.3 g/100 mL. Ratios of glucose to mannitol of 4-15 and of glucose to fructose of 0.8-1.0 are also characteristic of PJ. In addition, no sucrose should be present because of isomerase activity during commercial processing. Stable isotope ratio mass spectrometry as > -25 per thousand assures that there is no added corn or cane sugar added to PJ. Sorbitol was present at <0.025 g/100 mL; maltose and tartaric acid were not detected. The presence of the amino acid proline at >25 mg/L is indicative of added grape products. Malic acid at >0.1 g/100 mL indicates adulteration with apple, pear, grape, cherry, plum, or aronia juice. Other adulteration methods include the addition of highly concentrated aronia, blueberry, or blackberry juices or natural grape pigments to poor-quality juices to imitate the color of pomegranate juice, which results in abnormal anthocyanin profiles. To adjust the astringent taste of poor-quality juice or peel extract, addition of nonpomegranate sugars is a commonly detected adulteration method. The profile generated from these analyses combined with information from existing databases and published literature has been integrated into a validated IMAS for PJ, which can be utilized to detect PJ adulteration. In this survey of commercial pomegranate juices, only 6 of 23 strictly met all of the IMAS criteria.",
"title": "International multidimensional authenticity specification (IMAS) algorithm for detection of commercial pomegranate juice adulteration."
},
{
"docid": "MED-4642",
"text": "The role of diet in breast cancer (BC) risk is unclear. Fiber could reduce BC risk, through the enterohepatic circulation of estrogens. We examined the relationship between diet and sex hormones in postmenopausal women with or without BC. Thirty-one postmenopausal women (10 omnivores, 11 vegetarians, and 10 BC omnivores) were recruited. Dietary records (5 days) and hormone levels (3 days) were evaluated on 4 occasions over 1 yr. Vegetarians showed a lower fat/fiber ratio, a higher intake of total and cereal fiber (g/d)/body weight (kg), a significantly lower level of plasma estrone-sulfate, estradiol, free-estradiol, free-testosterone, and ring D oxygenated estrogens, and a significantly higher level of sex-hormone-binding-globulin than BC subjects. Fiber was consumed in slightly larger amounts by omnivores than by BC subjects. Omnivores had significantly lower plasma testosterone and estrone-sulfate but higher sex-hormone-binding-globulin than BC subjects. No difference was found for the urinary 16-oxygenated estrogens. However, the 2-MeO-E1/2-OH-E1 ratio was significantly lower in omnivores than in BC group. This ratio is positively associated with the fat/fiber ratio. In conclusion, testosterone may contribute to causing alterations in the levels of catechol estrogens and 16-oxygenated estrogens. The fat/fiber ratio appears to be useful in evaluating dietary effects on estrogen metabolism.",
"title": "Diets and hormonal levels in postmenopausal women with or without breast cancer."
},
{
"docid": "MED-4599",
"text": "Purpose To quantify the number of required hours of nutrition education at U.S. medical schools and the types of courses in which the instruction was offered, and to compare these results with results from previous surveys. Method The authors distributed to all 127 accredited U.S. medical schools (that were matriculating students at the time of this study) a two-page online survey devised by the Nutrition in Medicine Project at the University of North Carolina at Chapel Hill. From August 2008 through July 2009, the authors asked their contacts, most of whom were nutrition educators, to report the nutrition contact hours that were required for their medical students and whether those actual hours of nutrition education occurred in a designated nutrition course, within another course, or during clinical rotations. Results Respondents from 109 (86%) of the targeted medical schools completed some part of the survey. Most schools (103/109) required some form of nutrition education. Of the 105 schools answering questions about courses and contact hours, only 26 (25%) required a dedicated nutrition course; in 2004, 32 (30%) of 106 schools did. Overall, medical students received 19.6 contact hours of nutrition instruction during their medical school careers (range: 0–70 hours); the average in 2004 was 22.3 hours. Only 28 (27%) of the 105 schools met the minimum 25 required hours set by the National Academy of Sciences; in 2004, 40 (38%) of 104 schools did so. Conclusions The amount of nutrition education that medical students receive continues to be inadequate.",
"title": "Nutrition Education in U.S. Medical Schools: Latest Update of a National Survey"
},
{
"docid": "MED-4237",
"text": "OBJECTIVE: To evaluate the prevalence of benign prostatic hyperplasia (BPH) and prostatic cancer (CaP) in the mainland of China. METHODS: The incidence of BPH and CaP in urological hospital was investigated in 1997 in 26 provinces and 4 metropolises scattered over the mainland of China. The change of hospital incidences of BPH and CaP in the Institute of Urology, Beijing Medical University from 1951 to 1997 was also reviewed. RESULTS: The incidence of BPH and CaP in 1997 in 187 hospitals scattered over the mainland of China was 16.1% (15,459/95,749) and 1.5% (1389/95,749), respectively. The incidence of BPH and CaP in the Institute of Urology, Beijing University from 1951 to 1960 was 7.6% and 0.6%, respectively, while it was 18.5% and 3.4% from 1991 to 1997. CONCLUSION: The hospital incidence of BPH and CaP is rising rapidly in China, but CaP is still not a common disease in China.",
"title": "Epidemiological survey of benign prostatic hyperplasia and prostatic cancer in China."
},
{
"docid": "MED-2717",
"text": "The United States is in the midst of a significant public health problem that relates to obesity and inactivity. This epidemic has far-ranging consequences for our workforce and our children and shows no signs of slowing in the near future. Significant research has been performed on the effects of exercise for the reduction of body weight; results of most studies indicate that exercise alone has a small effect on body-weight reduction independent of caloric restriction. However, when combined with dietary restriction, exercise has a synergistic effect and enhances weight loss beyond the effect of diet alone. In addition, exercise has been shown to have significant beneficial effects on cardiovascular and metabolic risk factors independent of actual weight loss, and losing just a small amount of weight can have a significant beneficial effect on these parameters. Genetic factors related to obesity have been found to be positively modified when persons incorporate physical activity into their lifestyle. Sitting time appears to be an independent risk factor for the development of metabolic risk factors; persons who spend more time sitting and watching television have worse metabolic profiles, even if they achieve the recommended amount of physical activity per week, than do those who move about throughout the day. Exercise also is essential for the prevention of weight gain over a life span, although the amount required to prevent weight gain may be closer to twice the amount of exercise recommended by the current Physical Activity Guidelines for Americans (www.health.gov/paguidelines). In many ways, the physiatrist is the most well prepared of all the specialists to address the complex, multidimensional problems of obesity and inactivity. Copyright © 2012 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.",
"title": "The role of exercise in the treatment of obesity."
},
{
"docid": "MED-5102",
"text": "Due to the favourable health effects of LC n-3 PUFAs, marine products have been recognised as a food group of special importance in the human diet. However, seafood is susceptible to contamination by lipophilic organic pollutants. The objective of this study was to evaluate intake levels of PCDDs, PCDFs and dioxin-like PCBs, by a probabilistic Monte Carlo procedure, in relation to the recommendation on LC n-3 PUFAs given by Belgian Federal Health Council. Regarding the recommendation, two scenarios were developed differing in LC n-3 PUFAs intake: a 0.3 E% and a 0.46 E% scenario. Total exposure to dioxins and dioxin-like substances in the 0.3 E% LC n-3 PUFAs scenario ranges from 2.31 pg TEQ/kg bw/day at the 5th percentile, over 4.37 pg TEQ/kgbw/day at the 50th percentile to 8.41 pg TEQ/kgbw/day at the 95th percentile. In the 0.46 E% LC n-3 PUFAs scenario, 5, 50 and 95th percentile are exposed to 2.74, 5.52 and 9.98 pg TEQ/kgbw/day, respectively. Therefore, if the recommended LC n-3 PUFAs intake would be based on fish consumption as the only extra source, the majority of the study population would exceed the proposed health based guidance values for dioxins and dioxin-like substances.",
"title": "Simulated impact of a fish based shift in the population n--3 fatty acids intake on exposure to dioxins and dioxin-like compounds."
},
{
"docid": "MED-3955",
"text": "BACKGROUND Polybrominated Diphenyl Ethers (PBDEs), widely used as flame retardants since the 1970s, have exhibited endocrine disruption in experimental studies. Tetra- to hexa-BDE congeners are estrogenic, while hepta-BDE and 6-OH-BDE-47 are antiestrogenic. Most PBDEs also have antiandrogenic activity. It is not clear, however, whether PBDEs affect human reproduction. OBJECTIVES The analysis was designed to investigate the potential endocrine disruption of PBDEs on the age at menarche in adolescent girls. METHODS We analyzed the data from a sample of 271 adolescent girls (age 12–19 years) in the National Health and Nutrition Examination Survey (NHANES), 2003–2004. We estimated the associations between individual and total serum BDEs (BDE-28, -47, -99, -100, -153, and -154, lipid adjusted) and mean age at menarche. We also calculated the risk ratios (RRs) and 95% confidence intervals (CI) for menarche prior to age 12 years in relation to PBDE exposure. RESULTS The median total serum BDE concentration was 44.7 ng/g lipid. Higher serum PBDE concentrations were associated with slightly earlier ages at menarche. Each natural log unit of total BDEs was related to a change of −0.10 (95% CI: −0.33, 0.13) years of age at menarche and a RR of 1.60 (95% CI: 1.12, 2.28) for experiencing menarche before 12 years of age, after adjustment for potential confounders. CONCLUSION These data suggest high concentrations of serum PBDEs during adolescence are associated with a younger age of menarche.",
"title": "Serum PBDEs and Age at Menarche in Adolescent Girls: Analysis of the National Health and Nutrition Examination Survey 2003–2004"
},
{
"docid": "MED-5351",
"text": "Phytoestrogens have been linked to a risk of breast cancer. The main phytoestrogens in the Finnish diet are lignans, and enterolactone is quantitatively the most important circulating lignan. The purpose of this study was to examine the association between serum enterolactone and risk of breast cancer in Finnish women. The subjects were participants of the Kuopio Breast Cancer Study: This analysis concerns 194 breast cancer cases (68 premenopausal and 126 postmenopausal) who entered the study before diagnosis and 208 community-based controls. They completed a validated food frequency questionnaire referring to the previous 12 months and gave serum samples before the examinations. The measurement of serum enterolactone was performed by time-resolved fluoroimmunoassay. The statistical analyses were done by the logistic regression method. The mean serum enterolactone concentration was 20 nmol/l for the cases and 26 nmol/l for the controls (P 0.003). The mean serum enterolactone concentration in the lowest quintile was 3.0 nmol/l and 54.0 nmol/l in the highest. The odds ratio in the highest quintile of enterolactone values adjusted for all of the known risk factors for breast cancer was 0.38 (95% confidence interval,0.18-0.77; P for trend, 0.03). The inverse association between serum enterolactone and risk of breast cancer was seen both among premenopausal and postmenopausal women. High enterolactone level was associated with higher consumption of rye products and tea and higher intake of dietary fiber and vitamin E compared with those with low serum enterolactone values. Serum enterolactone level was significantly inversely associated with risk of breast cancer.",
"title": "Serum enterolactone and risk of breast cancer: a case-control study in eastern Finland."
},
{
"docid": "MED-1859",
"text": "Response surface methodology was used to investigate the effect and interactions of processing variables such as roselle extract (0.1-1.3%), soybean oil (5-20%) on physicochemical, textural and sensory properties of cooked pork patties. It was found that reduction in thickness, pH, L* and b* values decreased; however, water-holding capacity, reduction in diameter and a* values increased, respectively, as the amount of roselle increased. Soybean oil addition increased water-holding capacity, reduction in thickness, b* values of the patties. The hardness depended on the roselle and soybean oil added, as its linear effect was negative at p<0.01. The preference of color, tenderness, juiciness, and overall quality depend on the addition of roselle and soybean oil. The maximum overall quality score (5.42) was observed when 12.5 g of soybean oil and 0.7 g of roselle extract was added. The results of this optimization study would be useful for meat industry that tends to increase the product yield for patties using the optimum levels of ingredients by RSM. Copyright © 2013 Elsevier Ltd. All rights reserved.",
"title": "Roselle (Hibiscus sabdariffa L.) and soybean oil effects on quality characteristics of pork patties studied by response surface methodology."
},
{
"docid": "MED-3496",
"text": "The widely used food additive carrageenan (CGN) has been shown to induce intestinal inflammation, ulcerative colitis-like symptoms, or neoplasm in the gut epithelia in animal models, which are also clinical features of human inflammatory bowel disease. In this study, the effects of CGN on pro-inflammatory transcription factors NF-κB and early growth response gene 1 product (EGR-1) were evaluated in terms of human intestinal epithelial barrier integrity. Both pro-inflammatory transcription factors were elevated by CGN and only NF-κB activation was shown to be involved in the induction of pro-inflammatory cytokine interleukin-8. Moreover, the integrity of the in vitro epithelial monolayer under the CGN insult was maintained by both activated pro-inflammatory transcription factors NF-κB and EGR-1. Suppression of NF-κB or EGR-1 aggravated barrier disruption by CGN, which was associated with the reduced gene expression of tight junction component zonula occludens 1 and its irregular localization in the epithelial monolayer. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.",
"title": "Pro-inflammatory NF-κB and early growth response gene 1 regulate epithelial barrier disruption by food additive carrageenan in human intestinal epi..."
},
{
"docid": "MED-4650",
"text": "Aromatase is a cytochrome P450 enzyme (CYP19) and is the rate limiting enzyme in the conversion of androgens to estrogens. Suppression of in situ estrogen production through aromatase inhibition is the current treatment strategy for hormone-responsive breast cancers. Drugs that inhibit aromatase have been developed and are currently utilized as adjuvant therapy for breast cancer in post-menopausal women with hormone dependent breast cancer. Natural compounds have been studied extensively for important biologic effects such as antioxidant, anti-tumor and anti-viral effects. A significant number of studies have also investigated the aromatase inhibitory properties of a variety of plant extracts and phytochemicals. The identification of natural compounds that inhibit aromatase could be useful both from a chemopreventive standpoint and in the development of new aromatase inhibitory drugs. This review will discuss whole food extracts and the common classes of phytochemicals which have been investigated for potential aromatase inhibitory activity. We will review reported aromatase inhibition, kinetic data and possible structural variations that may inhibit or enhance the interaction of phytochemicals with the aromatase enzyme.",
"title": "Phytochemicals for breast cancer prevention by targeting aromatase."
},
{
"docid": "MED-2255",
"text": "Background Diet is a major source of cadmium intake among the non-smoking general population. Recent studies have determined that cadmium exposure may produce adverse health effects at lower exposure levels than previously predicted. We conducted a meta-analysis to combine and analyze the results of previous studies that have investigated the association of dietary cadmium intake and cancer risk. Methods We searched PubMed, EMBASE, and MEDLINE database for case-control and cohort studies that assessed the association of dietary cadmium intake and cancer risk. We performed a meta-analysis using eight eligible studies to summarize the data and summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using a random effects model. Results Overall, dietary cadmium intake showed no statistically significant association with cancer risk (RR = 1.10; 95% CI: 0.99–1.22, for highest vs. lowest dietary cadmium group). However, there was strong evidence of heterogeneity, and subgroup analyses were conducted using the study design, geographical location, and cancer type. In subgroup analyses, the positive associations between dietary cadmium intake and cancer risk were observed among studies with Western populations (RR = 1.15; 95% CI: 1.08–1.23) and studies investigating some hormone-related cancers (prostate, breast, and endometrial cancers). Conclusion Our analysis found a positive association between dietary cadmium intake and cancer risk among studies conducted in Western countries, particularly with hormone-related cancers. Additional experimental and epidemiological studies are required to verify our findings.",
"title": "Dietary Cadmium Intake and the Risk of Cancer: A Meta-Analysis"
},
{
"docid": "MED-3270",
"text": "Aging affects all organisms and its basic mechanisms are expected to be conserved across species. Oxidation of proteins has been proposed to be one of the basic mechanisms linking oxygen radicals with the basic aging process. If oxidative damage to proteins is involved in aging, long-lived animals (which age slowly) should show lower levels of markers of this kind of damage than short-lived ones. However, this possibility has not been investigated yet. In this study, steady-state levels of markers of different kinds of protein damage--oxidation (glutamic and aminoadipic semialdehydes), mixed glyco- and lipoxidation (carboxymethyl- and carboxyethyllysine), lipoxidation (malondialdehydelysine) and amino acid composition--were measured in the heart of eight mammalian species ranging in maximum life span (MLSP) from 3.5 to 46 years. Oxidation markers were directly correlated with MLSP across species. Mixed glyco- and lipoxidation markers did not correlate with MLSP. However, the lipoxidation marker malondialdehydelysine was inversely correlated with MLSP (r2=0.85; P<0.001). The amino acid compositional analysis revealed that methionine is the only amino acid strongly correlated MLSP and that such correlation is negative (r2=0.93; P<0.001). This trait may contribute to lower steady-state levels of oxidized methionine residues in cellular proteins. These results reinforce the notion that high longevity in homeothermic vertebrates is achieved in part by constitutively decreasing the sensitivity of both tissue proteins and lipids to oxidative damage. This is obtained by modifying the constituent structural components of proteins and lipids, selecting those less sensitive to oxidative modifications.",
"title": "Protein methionine content and MDA-lysine adducts are inversely related to maximum life span in the heart of mammals."
},
{
"docid": "MED-2163",
"text": "Gamma-glutamyltransferase (GGT) was measured in 1579 men, aged 20-54 years, and 1654 women, aged 20-49 years, screened for coronary risk factors. The distribution was right-skewed with medians 15 and 10 U/l for men and women, respectively. Less than 3.8% of the men and 0.8% of the women had GGT greater than or equal to 50 U/l. The low level of GGT matched well with the low mortality of cirrhosis and the modest use of alcohol in Norway. Multiple regression analysis for each sex showed a strong positive association with body mass index, use of alcohol and, unexpectedly, a negative association with coffee consumption, whereas serum triglycerides and the time since the last meal showed a weaker positive association. In women, use of oral contraceptives was positively associated with GGT.",
"title": "The Tromsø Heart Study: distribution of, and determinants for, gamma-glutamyltransferase in a free-living population."
},
{
"docid": "MED-921",
"text": "Tuberculosis (TB) is a major cause of mortality, responsible for 1·68 million deaths worldwide in 2009. The global prevalence of latent Mycobacterium tuberculosis infection is estimated to be 32%, and this carries a 5-20% lifetime risk of reactivation disease. The emergence of drug-resistant organisms necessitates the development of new agents to enhance the response to antimicrobial therapy for active TB. Vitamin D was used to treat TB in the pre-antibiotic era, and its active metabolite, 1,25-dihydoxyvitamin D, has long been known to enhance the immune response to mycobacteria in vitro. Vitamin D deficiency is common in patients with active TB, and several clinical trials have evaluated the role of adjunctive vitamin D supplementation in its treatment. Results of these studies are conflicting, reflecting variation between studies in baseline vitamin D status of participants, dosing regimens and outcome measures. Vitamin D deficiency is also recognised to be highly prevalent among people with latent M. tuberculosis infection in both high- and low-burden settings, and there is a wealth of observational epidemiological evidence linking vitamin D deficiency with increased risk of reactivation disease. Randomised controlled trials of vitamin D supplementation for the prevention of active TB have yet to be performed, however. The conduct of such trials is a research priority, given the safety and low cost of vitamin D supplementation, and the potentially huge public health consequences of positive results.",
"title": "Old wine in new bottles: vitamin D in the treatment and prevention of tuberculosis."
},
{
"docid": "MED-3589",
"text": "OBJECTIVE: To compare dietary habits in normospermic and oligoasthenoteratospermic patients attending a reproductive assisted clinic. DESIGN: An observational, analytical case-control study. SETTING: Private fertility clinics. PATIENT(S): Thirty men with poor semen quality (cases) and 31 normospermic control couples attending our fertility clinics. INTERVENTION(S): We recorded dietary habits and food consumption using a food frequency questionnaire adapted to meet specific study objectives. Analysis of semen parameters, hormone levels, Y microdeletions, and karyotypes were also carried out. MAIN OUTCOME MEASURE(S): Frequency of intake food items were registered in a scale with nine categories ranging from no consumption to repeated daily consumption. RESULT(S): Controls had a higher intake of skimmed milk, shellfish, tomatoes, and lettuce, and cases consumed more yogurt, meat products, and potatoes. In the logistic regression model cases had lower intake of lettuce and tomatoes, fruits (apricots and peaches), and significantly higher intake of dairy and meat processed products. CONCLUSION(S): Frequent intake of lipophilic foods like meat products or milk may negatively affect semen quality in humans, whereas some fruits or vegetables may maintain or improve semen quality.",
"title": "Food intake and its relationship with semen quality: a case-control study."
},
{
"docid": "MED-3690",
"text": "PURPOSE OF REVIEW: To critically appraise evidence on probiotic use for prevention and treatment of diarrhea in children and adults. RECENT FINDINGS: Several randomized controlled trials and meta-analyses suggested that probiotics are effective in primary and secondary prevention of gastroenteritis and its treatment. Selected Lactobacillus strains had a modest, although significant effect in primary prevention. Saccharomyces boulardii was effective in antibiotic-associated and in Clostridium difficile diarrhea. There is evidence that it might prevent diarrhea in day-care centers. Lactobacillus rhamnosus GG was associated with reduced diarrheal duration and severity, more evident in case of childhood Rotavirus diarrhea. Similar, although weaker, evidence was obtained with S. boulardii. Both strains are included in evidence-based recommendations for gastroenteritis management in children. Data on other Lactobacillus strains are preliminary. Probiotic efficacy was related to cause, early administration and bacterial load, and their mechanisms were associated with antiinfectious action in the intestine or, indirectly, to modulation of innate and adaptive immunity. SUMMARY: Probiotics have gained a role as adjunctive treatment of infantile gastroenteritis together with rehydration. Their efficacy is less convincing in adults, but promising in antibiotic-associated diarrhea. However, evidence of efficacy is limited to a few strains.",
"title": "Probiotics as prevention and treatment for diarrhea."
},
{
"docid": "MED-3781",
"text": "In this study, a panel of normal human prostate cells (HPCs) and tumor cells derived from metastases were studied by (1)H NMR spectroscopy to determine whether the malignant transformation of HPCs results in the elevation of choline compounds. Although an elevated choline signal has been observed previously in clinical studies, the contribution of the different Cho compounds to this elevation, as well as their quantification, has not been established until now. Here we have shown that HPCs derived from metastases exhibit significantly higher phosphocholine as well as glycerophosphocholine levels compared with normal prostate epithelial and stromal cells. Thus the elevation of the choline peak observed clinically in prostate cancer is attributable to an alteration of phospholipid metabolism and not simply to increased cell density, doubling time, or other nonspecific effects. Androgen deprivation of the androgen receptor-positive cell lines resulted in a significant increase of choline compounds after chronic androgen deprivation of the LNCaP cell line and in a decrease of choline compounds after a more acute androgen deprivation of the LAPC-4 cell line. These data strongly support the use of proton magnetic resonance spectroscopic imaging to detect the presence of prostate cancer for diagnosis, to detect response subsequent to androgen ablation therapy, and to detect recurrence.",
"title": "Detection of increased choline compounds with proton nuclear magnetic resonance spectroscopy subsequent to malignant transformation of human prosta..."
},
{
"docid": "MED-4698",
"text": "Females live longer than males. Work from our laboratory has shown that this may be due to the up-regulation of longevity-associated genes by estrogens. Estrogens bind to the estrogen receptors and subsequently activate the mitogen activated protein kinase and nuclear factor kappa B signalling pathways, resulting in an up-regulation of antioxidant enzymes. Estrogen administration, however, has serious undesirable effects and of course, cannot be administered to males because of its powerful feminizing effects. Thus, we tested the effect of genistein, a phytoestrogen of high nutritional importance whose structure is similar to estradiol, on the regulation of the expression of antioxidant, longevity-related genes and consequently on oxidant levels in mammary gland tumour cells in culture. Phytoestrogens mimic the protective effect of oestradiol using the same signalling pathway. The critical importance of up-regulating antioxidant genes, by hormonal and dietary manipulations, to increase longevity is discussed.",
"title": "Role of mitochondrial oxidative stress to explain the different longevity between genders: protective effect of estrogens."
},
{
"docid": "MED-2239",
"text": "OBJECTIVE: Human papillomavirus (HPV) infections remain a leading cause of mortality worldwide. In the U.S. strategies via screening and vaccination prevent HPV-associated cervical neoplasms, but consume immense healthcare costs. The spice component curcumin has potent anticancer and antiviral properties, which have been difficult to harness as a treatment, due to its poor systemic bioavailability. This project tests the possibility of developing a curcumin-based therapy for cervical cancer. METHODS: Using four HPV(+) cervical cancer cell lines and normal fibroblasts we first tested the selectivity and potency of curcumin in eliminating HPV(+) cells. Subsequently, we developed a curcumin-based cervical cream and tested its efficacy in eliminating apposed HPV(+) cells and also its possible side effects on the vaginal epithelium of healthy mice. RESULTS: Curcumin selectively eliminates a variety of HPV(+) cervical cancer cells (HeLa, ME-180, SiHa, and SW756), suppresses the transforming antigen E6, dramatically inhibits the expression of the pro-cancer protein epidermal growth factor receptor (EGFR), and concomitantly induces p53. Additionally, Vacurin, a uniform colloidal solution of curcumin in a clinically used amphipathic vaginal cream, eliminates apposed HeLa cells while suppressing the expression of EGFR. In mice, daily intravaginal application of Vacurin for three weeks produced no change in body weight and when the mice were sacrificed, the vaginal tract epithelium showed no Vacurin-evoked adverse effects. CONCLUSION: We have developed a curcumin-based vaginal cream, which effectively eradicates HPV(+) cancer cells and does not affect non-cancerous tissue. Our preclinical data support a novel approach for the treatment of cervical HPV infection. Copyright © 2012 Elsevier Inc. All rights reserved.",
"title": "A novel curcumin-based vaginal cream Vacurin selectively eliminates apposed human cervical cancer cells."
},
{
"docid": "MED-5046",
"text": "Epidemiological evidence suggests a role for tea catechins in reduction of chronic disease risk. However, stability of catechins under digestive conditions is poorly understood. The objective of this study was to characterize the effect of common food additives on digestive recovery of tea catechins. Green tea water extracts were formulated in beverages providing 4.5, 18, 23, and 3.5 mg per 100 mL epicatechin (EC), epigallocatechin (EGC), epigallocatechin-gallate (EGCG), and epicatechin-gallate (ECG), respectively. Common commercial beverage additives; citric acid (CA), BHT, EDTA, ascorbic acid (AA), milk (bovine, soy, and rice), and citrus juice (orange, grapefruit, lemon, and lime) were formulated into finished tea beverages at incremental dosages. Samples were then subjected to in vitro digestion simulating gastric and small intestinal conditions with pre- and post-digestion catechin profiles assessed by HPLC. Catechin stability in green tea was poor with <20% total catechins remaining post-digestion. EGC and EGCG were most sensitive with less, not double equals 10% recovery. Teas formulated with 50% bovine, soy, and rice milk increased total catechin recovery significantly to 52, 55, and 69% respectively. Including 30 mg AA in 250 mL of tea beverage significantly (p<0.05) increased catechin recovery of EGC, EGCG, EC, and ECG to 74, 54, 82, and 45% respectively. Juice preparation resulted in the highest recovery of any formulation for EGC (81-98%), EGCG (56-76%), EC (86-95%), and ECG (30-55%). These data provide evidence that tea consumption practices and formulation factors likely impact catechin digestive recovery and may result in diverse physiological profiles.",
"title": "Common tea formulations modulate in vitro digestive recovery of green tea catechins."
},
{
"docid": "MED-2945",
"text": "BACKGROUND: To investigate whether the Chinese lacto-vegetarian diet has protective effects on metabolic and cardiovascular disease (CVD). METHODS: One hundred sixty-nine healthy Chinese lacto-vegetarians and 126 healthy omnivore men aged 21-76 years were enrolled. Anthropometric indexes, lipid profile, insulin sensitivity, pancreatic β cell function, and intima-media thickness (IMT) of carotid arteries were assessed and compared. Cardiovascular risk points and probability of developing CVD in 5-10 years in participants aged 24-55 years were calculated. RESULTS: Compared with omnivores, lacto-vegetarians had remarkably lower body mass index, systolic and diastolic blood pressure, and serum levels of triglyceride, total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, γ-glutamyl transferase, serum creatinine, uric acid, fasting blood glucose, as well as lower total cholesterol/high-density lipoprotein cholesterol ratio. Vegetarians also had higher homeostasis model assessment β cell function and insulin secretion index and thinner carotid IMT than the omnivores did. These results corresponded with lower cardiovascular risk points and probability of developing CVD in 5-10 years in vegetarians 24-55 years old. CONCLUSIONS: In healthy Chinese men, the lacto-vegetarian diet seems to exert protective effects on blood pressure, lipid profiles, and metabolic parameters and results in significantly lower carotid IMT. Lower CVD risks found in vegetarians also reflect the beneficial effect of the Chinese lacto-vegetarian diet.",
"title": "Chinese lacto-vegetarian diet exerts favorable effects on metabolic parameters, intima-media thickness, and cardiovascular risks in healthy men."
},
{
"docid": "MED-5340",
"text": "In Asia, vegetarianism is a well-established eating behavior. It appears that the adoption of a vegan diet leads to a lessening of several health risk factors. Although vegetarianism has some notable effects on the hematological system, the effect on the nephrological system has not been well clarified. The pattern of renal function parameters was studied in 25 Thai vegans compared with 25 non-vegetarians. Of the studied parameters, it was found that urine protein was significantly different (p < 0.05) in vegans and controls. Vegans had significantly lower urine protein level.",
"title": "Renal function parameters of Thai vegans compared with non-vegans."
},
{
"docid": "MED-3054",
"text": "The relationship between overeating, substance abuse and (behavioral) addiction is controversial. Medically established forms of addiction so far pertain to substance use disorders only. But the preliminary Diagnostic and Statistical Manual for Mental Disorders V (DSM V) suggests replacing the previous category 'Substance-Related Disorders' with 'Addiction and Related Disorders', thus for the first time allowing the diagnosis of behavioral addictions. In the past psychiatrists and psychologists have been reluctant to systematically delineate and classify the term behavioral addiction. However, there is a broad overlap between chemical and behavioral addiction including phenomenological, therapeutic, genetic, and neurobiological aspects. It is of interest to point out that the hormone leptin in itself has a pronounced effect on the reward system, thus suggesting an indirect link between overeating and 'chemical' addiction. Thus, leptin-deficient individuals could be classified as fulfilling criteria for food addiction. In our overview we first review psychological findings in chemical (substance-based) and subsequently in behavioral addiction to analyze the overlap. We discuss the diagnostic validity of food addiction, which in theory can be chemically and/or behaviorally based. Copyright © 2012 S. Karger GmbH, Freiburg.",
"title": "Does food addiction exist? A phenomenological discussion based on the psychiatric classification of substance-related disorders and addiction."
},
{
"docid": "MED-969",
"text": "The endothelium is a highly metabolically active organ that is involved in many physiological processes, including the control of vasomotor tone, barrier function, leukocyte adhesion and trafficking, inflammation, and hemostasis. Endothelial cell phenotypes are differentially regulated in space and time. Endothelial cell heterogeneity has important implications for developing strategies in basic research, diagnostics and therapeutics. The goals of this review are to: (i) consider mechanisms of endothelial cell heterogeneity; (ii) discuss the bench-to-bedside gap in endothelial biomedicine; (iii) revisit definitions for endothelial cell activation and dysfunction; and (iv) propose new goals in diagnosis and therapy. Finally, these themes will be applied to an understanding of vascular bed-specific hemostasis.",
"title": "Spatial and temporal dynamics of the endothelium."
}
] |
5ae7c0115542993210983f33
|
Riccardo Cocchi is a six-time Latin Dance Champion with his partner, born when?
|
[
{
"docid": "51576314",
"text": "Riccardo Cocchi (born December 7, 1977, Terni, Italy) is a six-time Latin Dance Champion, with his partner, Yulia Zagoruychenko. Currently, he resides in and represents the United States of America. When not busy competing, Riccardo is available for coaching.",
"title": ""
},
{
"docid": "27207486",
"text": "Yulia Zagoruychenko (born September 11, 1981) is the current World Latin Dance Champion, with her partner, Riccardo Cocchi.",
"title": ""
}
] |
[
{
"docid": "24782435",
"text": "Michael Malitowski is a ballroom dancer, a former World Latin Dance Champion with his partner Joanna Leunis. Michael (christened \"Michał\") was born 28 May 1980, in Zielona Góra, Poland. His partnership with Leunis has, since 2002, resulted in a string of victories: in 2008 and 2009 they won the World Professional Latin title, and in 2012 they won first place in Latin dance at the Blackpool Dance Festival. This is the prestigious Open British Championships held every year in Blackpool, England. Before that, he won the Polish Latin dance championship four times with Iwona Golczak.",
"title": ""
},
{
"docid": "9172906",
"text": "Gaynor Fairweather is a British professional ballroom dancer. She and her partner, Donnie Burns, were 14-time Professional World Latin Dance Champions and 11 times Professional International Latin American Dance Champions. This is by some way the record number of wins in both these top competitions. On their retirement from competition dancing they were both appointed Members of the Order of the British Empire (MBE) for services to the performing arts.",
"title": ""
},
{
"docid": "14954895",
"text": "Valentin Aleksandrovich \"Val\" Chmerkovskiy (Ukrainian: Валентин Олекса́ндрович Чмерковський ; born March 24, 1986) is a Ukrainian-American professional dancer, best known for his appearances on the U.S. version of \"Dancing with the Stars\", which he won twice. Chmerkovskiy is a two-time World Latin Dance Champion (Junior and Youth) and a 14-time U.S. National Latin Dance champion.",
"title": ""
},
{
"docid": "27946754",
"text": "Jillian La Valette (born Maida Vale, London, 19 August 1934) is a professional ballroom dancer and teacher. With her dance partner James Arnell she won the professional International Latin American Dance Championship six times between 1955 and 1965.",
"title": ""
},
{
"docid": "10456953",
"text": "Martin Lidberg (born 1 February 1973, in Farsta in the south of Stockholm) is a highly decorated Swedish wrestler. He is a world champion, two-time European champion as well as 19-time Swedish champion. He has competed in the olympics three times (last time in Athens). In 2007 he won Let's Dance 2007 in Sweden together with his dancing partner Cecilia Ehrling, defeating Tobbe Blom, host of Idol 2005. Lidberg and Ehrling represented Sweden in the Eurovision Dance Contest 2007, where they placed 14th.",
"title": ""
},
{
"docid": "12932110",
"text": "Gregory Merriman (born 3 October 1988) is an Australian ice dancer. With partner Danielle O'Brien, he is a six-time Australian senior national champion and three-time junior national champion. They have competed at the World Championships and Four Continents Championships since 2008, and have competed at three World Junior Championships. They became the first Australian ice dancers to reach the free dance at a World Championships and the second Ice Dance couple from Australia to compete at the Winter Olympics.",
"title": ""
},
{
"docid": "5704891",
"text": "Marcus van Teijlingen (born 20 March 1973 in Rijnsburg) is a Dutch dance instructor and professional Latin-American dancer. His regular dance partner was Nathalie Kip. He has been working full-time as a dance instructor in Groningen since 2004.",
"title": ""
},
{
"docid": "12932090",
"text": "Danielle O'Brien (born 7 February 1990) is an Australian ice dancer. With partner Gregory Merriman, she is a six-time Australian senior national champion and three-time junior national champion. They have competed at the World Championships and Four Continents Championships since 2008, and have competed at three World Junior Championships. They became the first Australian ice dancers to reach the free dance at a World Championships.",
"title": ""
},
{
"docid": "26976117",
"text": "Ekaterina Vaganova (born January 9, 1988) is a Russian dancer. She is the World champion on the Ballroom and Latin American dances. She was two-time Champion of Russia, four-time Champion of Italy, two-time vice-champion of the World in Youth Latin, IDSF, finalist of the World and European championships in IDSF, champion of the World 2009 in IDSA and IDU versions and champion of the Europe WDC Latin 2009.",
"title": ""
},
{
"docid": "11940854",
"text": "The Champion Ballroom Academy (founded April 1990) is a dance studio in San Diego, California. The studio's main specialties are social partner-dancing, competitive ballroom dance (aka. Dancesport) and the Latin-dance-based aerobic program called Core Rhythms.",
"title": ""
},
{
"docid": "1345789",
"text": "Zhao Hongbo (; born September 22, 1973) is a male Chinese pair skater. With his partner and wife Shen Xue, Zhao is the 2010 Olympic champion, the 2002 & 2006 Olympic bronze medalist, a three-time (2002, 2003 & 2007) World champion, a three-time (1999, 2003 & 2007) Four Continents Champion and a six-time (1998, 1999, 2003, 2004, 2006 & 2009) Grand Prix Final champion.",
"title": ""
},
{
"docid": "30862805",
"text": "Sara Hurtado (born 3 November 1992) is a Spanish ice dancer who skates with Kirill Khaliavin. With former partner Adrià Díaz, she won four senior international medals. Hurtado and Diaz were the first dance team to represent Spain in ISU competition and the first to qualify for the Olympics. Hurtado is a six-time Spanish national champion, five times with Díaz and once with Khaliavin.",
"title": ""
},
{
"docid": "8735619",
"text": "Andrew Cuerden is a Latin dancer. Born in Zimbabwe, and growing up in South Africa, Cuerden moved to England to further his dance career in 1996. Dancing with partner Hanna Haarala they reached 4th place in the UK amateur Latin rankings, before turning pro on February 5. He, along with Haarala was chosen to tutor a celebrity in the third series of \"Strictly Come Dancing\" - partnered with Jaye Jacobs he was eliminated in week 2, but performed in many professional demonstrations.",
"title": ""
},
{
"docid": "2305521",
"text": "Bryan Watson (born 18 April 1969) was nine times Professional World Latin Dance Champion. He also won the International Latin American Championship five times.",
"title": ""
},
{
"docid": "47295833",
"text": "Ginepro Cocchi (13 October 1908 – 6 March 1939), born Antonio Cocchi, was an Italian Roman Catholic priest who became a member of the Capuchin order. He served in the missions in China until 1939 when he was killed out of hatred for the faith. He took the name of \"Ginepro\" after admittance into the Capuchin order.",
"title": ""
},
{
"docid": "7976751",
"text": "Anna Cappellini (born 19 February 1987) is an Italian ice dancer. With partner Luca Lanotte, she is the 2014 World champion, the 2014 European champion, the 2015 Cup of China champion and a thirteen-time medalist on the Grand Prix series, and a six-time Italian national champion (2012–17).",
"title": ""
},
{
"docid": "7976847",
"text": "Luca Lanotte (born 30 July 1985) is an Italian ice dancer. With partner Anna Cappellini, he is the 2014 World champion, the 2014 European champion, the 2015 Cup of China champion and a thirteen-time medalist on the Grand Prix series, and a six-time Italian national champion (2012–17).",
"title": ""
},
{
"docid": "33271160",
"text": "Daniel Eaton (born March 26, 1992) is an American ice dancer. With former partner Alexandra Aldridge, he is the 2014 Four Continents bronze medalist, a two-time (2012, 2013) World Junior bronze medalist, the 2012 JGP Final bronze medalist, a two-time U.S. national junior champion and 2010 Novice National Ice Dance Champion. Danielle Thomas and Daniel Eaton became partners, 2015. Their competitive season placed them first at the Ice Challenge, Graz, Austria, first at Mid-Western Sectionals and sixth at their US Championship. Season 2016 began with first place finish at the Lake Placid International Ice Dance Championship and second place finish at the First Annual Dance Chicago competition.",
"title": ""
},
{
"docid": "26535261",
"text": "Eric Radford (born January 27, 1985) is a Canadian pair skater. With partner Meagan Duhamel, he is a two-time world champion (2015, 2016), an Olympic silver medalist in the team event, a two-time Four Continents champion (2013, 2015), the 2014–15 Grand Prix Final champion, and a six-time Canadian national champion (2012–17).",
"title": ""
},
{
"docid": "8239402",
"text": "Meagan Duhamel (born December 8, 1985) is a Canadian pair skater. With partner Eric Radford, she is a two-time world champion (2015, 2016), an Olympic silver medalist in the team event, two-time Four Continents champion (2013, 2015), 2014–15 Grand Prix Final champion, and six-time Canadian national champion (2012–17).",
"title": ""
},
{
"docid": "41280953",
"text": "Nancy Wallin Flores Lessler, better known as Nancy Flores, is an American professional dancer, actor, and mural painter. Lessler is a two-time champion of the Fred Astaire national competition in ballroom dancing. She has also appeared in the U.S Air Force Band's Guest Artist Series when it focused on dancing. Flores and dancing partner Gary Gekhman, who appeared on ABC-TV's \"Dancing with the Stars,\" received an award for their participation from Major General Darren W. McDew.",
"title": ""
},
{
"docid": "365974",
"text": "Latin dance is a general label, and a term in partner dance competition jargon. It refers to types of ballroom dance and folk dance that (with few exceptions) originated in Latin America.",
"title": ""
},
{
"docid": "5841835",
"text": "Natalia Vladimirovna Linichuk (Russian: ; born 6 February 1956) is a Russian ice dancing coach and former competitive ice dancer for the Soviet Union. With partner Gennadi Karponosov, she is the 1980 Olympic champion and a two-time World champion.",
"title": ""
},
{
"docid": "8618186",
"text": "Walter William Laird (26 July 1920 – 30 May 2002) was a major influence in the development of Latin American dancing in Britain after the Second World War. He was World Professional Latin Dance Champion three times. He coached many successful dancers including Allan Tornsberg, Vibeke Toft, Espen Salberg, Jukka Haapalainen, Sirpa Suutari and Donnie Burns, Peter Maxwell & Lynn Harman were amongst his first major champions and a couple on which much of his ultimate technique was developed. Laird was a Fellow and Examiner of the IDTA, and until 2000, he was Secretary (and later President) of the Ballroom Dancers' Federation.",
"title": ""
},
{
"docid": "7847641",
"text": "Meryl Elizabeth Davis (born January 1, 1987) is an American ice dancer. With partner Charlie White, she is the 2014 Olympic champion, the 2010 Olympic silver medalist, a two-time (2011, 2013) World champion, five-time Grand Prix Final champion (2009–2013), three-time Four Continents champion (2009, 2011, 2013) and six-time U.S. national champion (2009–2014). They also won a bronze medal in the team event at the 2014 Winter Olympics.",
"title": ""
},
{
"docid": "1345772",
"text": "Shen Xue (; born November 13, 1978) is a female Chinese pair skater. With her partner and husband Zhao Hongbo, Shen is the 2010 Olympic champion, the 2002 & 2006 Olympic bronze medalist, a three-time (2002, 2003 & 2007) World champion, a three-time (1999, 2003 & 2007) Four Continents Champion and a six-time (1998, 1999, 2003, 2004, 2006 & 2009) Grand Prix Final champion.",
"title": ""
},
{
"docid": "7847652",
"text": "Charles Allen \"Charlie\" White, Jr. (born October 24, 1987) is an American ice dancer. With partner Meryl Davis, he is the 2014 Olympic Champion, the 2010 Olympic silver medalist, a two-time (2011, 2013) World champion, five-time Grand Prix Final champion (2009–2013), three-time Four Continents champion (2009, 2011, 2013) and six-time U.S. national champion (2009–2014). They also won a bronze medal in the team event at the 2014 Winter Olympics.",
"title": ""
},
{
"docid": "14235122",
"text": "Bernard Ford, MBE, (born in Birmingham) is an English former ice dancer. With partner Diane Towler, he is a four-time (1966–1969) World, European, and British champion. He is also a World Professional ice dancing champion. He later became a coach and choreographer.",
"title": ""
},
{
"docid": "28481110",
"text": "Tim Giesen (born July 26, 1988 in Wuppertal) is a German ice dancer. He started skating at age six and skated in singles until 11 when he switched to ice dance. His partners were Frauke Stein, Saskia Brall, Jana Werner, and Christina Beier, before teaming up with Stefanie Frohberg in April 2009. Giesen retired from competitive skating in 2011 to focus on his university studies.",
"title": ""
},
{
"docid": "24782608",
"text": "Joanna Leunis, born 22 May 1981 in Rocourt, Liège, Belgium, is a professional Latin ballroom dancer. With Michael Malitowski, she is a former professional World Latin Dance Champion and the current International Latin American Dance Champion. The couple represented Poland until 2011, representing England from then on.",
"title": ""
}
] |
12
|
40mg/day dosage of folic acid and 2mg/day dosage of vitamin B12 does not affect chronic kidney disease (CKD) progression.
|
[
{
"docid": "33409100",
"text": "CONTEXT High plasma homocysteine levels are a risk factor for mortality and vascular disease in observational studies of patients with chronic kidney disease. Folic acid and B vitamins decrease homocysteine levels in this population but whether they lower mortality is unknown. OBJECTIVE To determine whether high doses of folic acid and B vitamins administered daily reduce mortality in patients with chronic kidney disease. DESIGN, SETTING, AND PARTICIPANTS Double-blind randomized controlled trial (2001-2006) in 36 US Department of Veterans Affairs medical centers. Median follow-up was 3.2 years for 2056 participants aged 21 years or older with advanced chronic kidney disease (estimated creatinine clearance < or =30 mL/min) (n = 1305) or end-stage renal disease (n = 751) and high homocysteine levels (> or = 15 micromol/L). INTERVENTION Participants received a daily capsule containing 40 mg of folic acid, 100 mg of pyridoxine hydrochloride (vitamin B6), and 2 mg of cyanocobalamin (vitamin B12) or a placebo. MAIN OUTCOME MEASURES The primary outcome was all-cause mortality. Secondary outcomes included myocardial infarction (MI), stroke, amputation of all or part of a lower extremity, a composite of these 3 plus all-cause mortality, time to initiation of dialysis, and time to thrombosis of arteriovenous access in hemodialysis patients. RESULTS Mean baseline homocysteine level was 24.0 micromol/L in the vitamin group and 24.2 micromol/L in the placebo group. It was lowered 6.3 micromol/L (25.8%; P < .001) in the vitamin group and 0.4 micromol/L (1.7%; P = .14) in the placebo group at 3 months, but there was no significant effect on mortality (448 vitamin group deaths vs 436 placebo group deaths) (hazard ratio [HR], 1.04; 95% CI, 0.91-1.18). No significant effects were demonstrated for secondary outcomes or adverse events: there were 129 MIs in the vitamin group vs 150 for placebo (HR, 0.86; 95% CI, 0.67-1.08), 37 strokes in the vitamin group vs 41 for placebo (HR, 0.90; 95% CI, 0.58-1.40), and 60 amputations in the vitamin group vs 53 for placebo (HR, 1.14; 95% CI, 0.79-1.64). In addition, the composite of MI, stroke, and amputations plus mortality (P = .85), time to dialysis (P = .38), and time to thrombosis in hemodialysis patients (P = .97) did not differ between the vitamin and placebo groups. CONCLUSION Treatment with high doses of folic acid and B vitamins did not improve survival or reduce the incidence of vascular disease in patients with advanced chronic kidney disease or end-stage renal disease. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00032435.",
"title": "Effect of homocysteine lowering on mortality and vascular disease in advanced chronic kidney disease and end-stage renal disease: a randomized controlled trial."
}
] |
[
{
"docid": "11705328",
"text": "BACKGROUND Lowering serum homocysteine levels with folic acid is expected to reduce mortality from ischemic heart disease. Homocysteine reduction is known to be maximal at a folic acid dosage of 1 mg/d, but the effect of lower doses (relevant to food fortification) is unclear. METHODS We randomized 151 patients with ischemic heart disease to 1 of 5 dosages of folic acid (0.2, 0.4, 0.6, 0.8, and 1.0 mg/d) or placebo. Fasting blood samples for serum homocysteine and serum folate analysis were taken initially, after 3 months of supplementation, and 3 months after folic acid use was discontinued. RESULTS Median serum homocysteine level decreased with increasing folic acid dosage, to a maximum at 0.8 mg of folic acid per day, when the homocysteine reduction (placebo adjusted) was 2.7 micromol/L (23%), similar to the known effect of folic acid dosages of 1 mg/d and above. The higher a person's initial serum homocysteine level, the greater was the response to folic acid, but there were statistically significant reductions regardless of the initial level. Serum folate level increased approximately linearly (5.5 nmol/L for every 0.1 mg of folic acid). Within-person fluctuations over time in serum homocysteine levels, measured in the placebo group, were large compared with the effect of folic acid, indicating that monitoring of the reduction in an individual is impractical. CONCLUSIONS A dosage of folic acid of 0.8 mg/d appears necessary to achieve the maximum reduction in serum homocysteine level across the range of homocysteine levels in the population. Current US food fortification levels will achieve only a small proportion of the achievable homocysteine reduction.",
"title": "Randomized trial of folic acid supplementation and serum homocysteine levels."
},
{
"docid": "26025820",
"text": "The rat kidney ablation and infarction (A/I) model of subtotal or 5/6th nephrectomy is the most commonly studied model of nondiabetic chronic kidney disease (CKD). The A/I kidney at 1 wk exhibits reductions in kidney function, as determined by glomerular filtration rate, and diminished metabolic efficiency as determined by oxygen consumption per sodium transport (QO2/TNa). As renoprotective AMPK activity is affected by metabolic changes and cellular stress, we evaluated AMPK activity in this model system. We show that these early pathophysiological changes are accompanied by a paradoxical decrease in AMPK activity. Over time, these kidney parameters progressively worsen with extensive kidney structural, functional, metabolic, and fibrotic changes observed at 4 wk after A/I. We show that induction of AMPK activity with either metformin or 5-aminoimidazole-4-carboxamide ribonucleotide increases AMPK activity in this model and also corrects kidney metabolic inefficiency, improves kidney function, and ameliorates kidney fibrosis and structural alterations. We conclude that AMPK activity is reduced in the subtotal nephrectomy model of nondiabetic CKD, that altered regulation of AMPK is coincident with the progression of disease parameters, and that restoration of AMPK activity can suppress the progressive loss of function characteristic of this model. We propose that induction of AMPK activity may prove an effective therapeutic target for the treatment of nondiabetic CKD.",
"title": "Induction of AMPK activity corrects early pathophysiological alterations in the subtotal nephrectomy model of chronic kidney disease."
},
{
"docid": "37424881",
"text": "OBJECTIVE Folate and vitamin B12 are two vital regulators in the metabolic process of homocysteine, which is a risk factor of atherothrombotic events. Low folate intake or low plasma folate concentration is associated with increased stroke risk. Previous randomized controlled trials presented discordant findings in the effect of folic acid supplementation-based homocysteine lowering on stroke risk. The aim of the present review was to perform a meta-analysis of relevant randomized controlled trials to check the how different folate fortification status might affect the effects of folic acid supplementation in lowering homocysteine and reducing stroke risk. DESIGN Relevant randomized controlled trials were identified through formal literature search. Homocysteine reduction was compared in subgroups stratified by folate fortification status. Relative risks with 95 % confidence intervals were used as a measure to assess the association between folic acid supplementation and stroke risk. SETTING The meta-analysis included fourteen randomized controlled trials, SUBJECTS A total of 39 420 patients. RESULTS Homocysteine reductions were 26·99 (sd 1·91) %, 18·38 (sd 3·82) % and 21·30 (sd 1·98) %, respectively, in the subgroups without folate fortification, with folate fortification and with partial folate fortification. Significant difference was observed between the subgroups with folate fortification and without folate fortification (P=0·05). The relative risk of stroke was 0·88 (95 % CI 0·77, 1·00, P=0·05) in the subgroup without folate fortification, 0·94 (95 % CI 0·58, 1·54, P=0·82) in the subgroup with folate fortification and 0·91 (95 % CI 0·82, 1·01, P=0·09) in the subgroup with partial folate fortification. CONCLUSIONS Folic acid supplementation might have a modest benefit on stroke prevention in regions without folate fortification.",
"title": "The effect of folate fortification on folic acid-based homocysteine-lowering intervention and stroke risk: a meta-analysis."
},
{
"docid": "23377475",
"text": "The previous conventional wisdom that survivors of acute kidney injury (AKI) tend to do well and fully recover renal function appears to be flawed. AKI can cause end-stage renal disease (ESRD) directly, and increase the risk of developing incident chronic kidney disease (CKD) and worsening of underlying CKD. In addition, severity, duration, and frequency of AKI appear to be important predictors of poor patient outcomes. CKD is an important risk factor for the development and ascertainment of AKI. Experimental data support the clinical observations and the bidirectional nature of the relationships between AKI and CKD. Reductions in renal mass and nephron number, vascular insufficiency, cell cycle disruption, and maladaptive repair mechanisms appear to be important modulators of progression in patients with and without coexistent CKD. Distinction between AKI and CKD may be artificial. Consideration should be given to the integrated clinical syndrome of diminished GFR, with acute and chronic stages, where spectrum of disease state and outcome is determined by host factors, including the balance of adaptive and maladaptive repair mechanisms over time. Physicians must provide long-term follow-up to patients with first episodes of AKI, even if they presented with normal renal function.",
"title": "Acute kidney injury and chronic kidney disease: an integrated clinical syndrome."
},
{
"docid": "43557480",
"text": "The aim of this study was the long-term retrospective analysis of chronic kidney disease (CKD) progression in children, especially with regard to the presence of hypertension (HTN). The average rate of progression of CKD was higher in patients with HTN than without HTN. Hypertension treatment requires multidrug schemes which need to be intensified with extended time of CKD duration.",
"title": "Arterial hypertension and progression of chronic kidney disease in children during 10-year ambulatory observation."
},
{
"docid": "19804204",
"text": "BACKGROUND AND OBJECTIVES Children with chronic kidney disease (CKD) are at risk for cognitive dysfunction, and over half have hypertension. Data on the potential contribution of hypertension to CKD-associated neurocognitive deficits in children are limited. Our objective was to determine whether children with CKD and elevated BP (EBP) had decreased performance on neurocognitive testing compared with children with CKD and normal BP. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This was a cross-sectional analysis of the relation between auscultatory BP and neurocognitive test performance in children 6 to 17 years enrolled in the Chronic Kidney Disease in Children (CKiD) project. RESULTS Of 383 subjects, 132 (34%) had EBP (systolic BP and/or diastolic BP ≥90(th) percentile). Subjects with EBP had lower mean (SD) scores on Wechsler Abbreviated Scales of Intelligence (WASI) Performance IQ than those with normal BP (normal BP versus EBP, 96.1 (16.7) versus 92.4 (14.9), P = 0.03) and WASI Full Scale IQ (97.0 (16.2) versus 93.4 (16.5), P = 0.04). BP index (subject's BP/95(th) percentile BP) correlated inversely with Performance IQ score (systolic, r = -0.13, P = 0.01; diastolic, r = -0.19, P < 0.001). On multivariate analysis, the association between lower Performance IQ score and increased BP remained significant after controlling for demographic and disease-related variables (EBP, β = -3.7, 95% confidence interval [CI]: -7.3 to -0.06; systolic BP index, β = -1.16 to 95% CI: -2.1, -0.21; diastolic BP index, β = -1.17, 95% CI: -1.8 to -0.55). CONCLUSIONS Higher BP was independently associated with decreased WASI Performance IQ scores in children with mild-to-moderate CKD.",
"title": "Casual blood pressure and neurocognitive function in children with chronic kidney disease: a report of the children with chronic kidney disease cohort study."
},
{
"docid": "21636085",
"text": "BACKGROUND Increased plasma homocysteine is associated with coronary artery disease, peripheral vascular disease and venous thrombosis. Folic acid is the most effective therapy for reducing homocysteine levels. The lowest effective supplement of folic acid is not known, particularly for the elderly who have the highest prevalence of these conditions. AIM To explore the effects of daily supplements of 0, 50, 100, 200, 400 and 600 microg folic acid on plasma homocysteine in an elderly population. DESIGN Randomized double-blind placebo-controlled trial. METHODS Participants (n=368) aged 65-75 years were randomly allocated to receive one of the treatments for 6 weeks. Plasma homocysteine was recorded after 3 weeks and 6 weeks of supplementation. RESULTS Only the 400 microg and 600 microg groups had significantly lower homocysteine levels compared to placebo (p=0.038 and p<0.001, respectively). Using multiple linear regression and each individual's total folic acid intake (diet plus supplement), a total daily folic acid intake of 926 microg per day would be required to ensure that 95% of the elderly population would be without cardiovascular risk from folate deficiency. DISCUSSION A daily folic acid intake of 926 microg is unlikely to be achieved by diet alone. Individual supplementation or fortification of food with folic acid will be required to reach this target.",
"title": "The effect of folic acid supplementation on plasma homocysteine in an elderly population."
},
{
"docid": "24865781",
"text": "Forty-one recurrent tension headache sufferers were randomly assigned to either cognitive-behavioral therapy (administered in a primarily home-based treatment protocol) or to amitriptyline therapy (with dosage individualized at 25, 50, or 75 mg/day). Cognitive-behavioral therapy and amitriptyline each yielded clinically significant improvements in headache activity, both when improvement was assessed with patient daily recordings (56% and 27% reduction in headache index, respectively), and when improvement was assessed with neurologist ratings of clinical improvement (94% and 69% of patients rated at least moderately improved, respectively). In instances where differences in treatment effectiveness were observed (headache index, somatic complaints, perceptions of control of headache activity), cognitive-behavioral therapy yielded somewhat more positive outcomes than did amitriptyline. Neither treatment, however, eliminated headache problems.",
"title": "A comparison of pharmacological (amitriptyline HCL) and nonpharmacological (cognitive-behavioral) therapies for chronic tension headaches."
},
{
"docid": "8318922",
"text": "Strict blood pressure (BP) control is reportedly important for the management of hypertensive patients with chronic kidney disease (CKD). The purpose of this cross-sectional study was to examine whether the variables of ambulatory BP and the heart rate (HR) profile, central hemodynamics, and arterial stiffness were closely related to the renal function parameters (urine albumin excretion rate [UACR] and estimated glomerular filtration rate [eGFR]) observed in 25 consecutive hospitalized hypertensive patients with CKD. There were significant positive relationships between UACR and 24-hour, daytime, and nighttime ambulatory systolic BP. In addition, there were significant negative relationships between UACR and 24-hour and daytime HR variability. The circulating B-type natriuretic peptide level and hemoglobin A1c were also positively related to UACR. With respect to eGFR, although the 24-hour and nighttime HR variability were positively associated with eGFR, the circulating pentosidine and nighttime HR had a negative relationship with eGFR. On the other hand, central hemodynamics and arterial stiffness did not exhibit any significant association with renal function parameters. These results indicate that ambulatory BP and the HR profile are closely modulated by renal function deterioration. Further studies are needed to investigate the causal relationship between ambulatory BP and the HR profile and renal function parameters in hypertensive patients with CKD.",
"title": "Relationship of ambulatory blood pressure and the heart rate profile with renal function parameters in hypertensive patients with chronic kidney disease."
},
{
"docid": "8446259",
"text": "Background: Vascular calcification (VC), in which vascular smooth muscle cells (VSMCs) undergo a phenotypic transformation into osteoblast-like cells, is one of the emergent risk factors for the accelerated atherosclerosis process characteristic of chronic kidney disease (CKD). Phosphate is an important regulator of VC. Methods: The expression of different smooth muscle cell or osteogenesis markers in response to high concentrations of phosphate or exogenous bone morphogenetic protein 2 (BMP-2) was examined by qRT-PCR and western blotting in rat VSMCs. Osteocalcin secretion was measured by radioimmunoassay. Differentiation and calcification of VSMCs were examined by alkaline phosphatase (ALP) activity assay and Alizarin staining. Short hairpin RNA-mediated silencing of β-catenin was performed to examine the involvement of Wnt/β-catenin signaling in VSMC calcification and osteoblastic differentiation induced by high phosphate or BMP-2. Apoptosis was determined by TUNEL assay and immunofluorescence imaging. Results: BMP-2 serum levels were significantly higher in CKD patients than in controls. High phosphate concentrations and BMP-2 induced VSMC apoptosis and upregulated the expression of β-catenin, Msx2, Runx2 and the phosphate cotransporter Pit1, whereas a BMP-2 neutralization antibody reversed these effects. Knockdown of β-catenin abolished the effect of high phosphate and BMP-2 on VSMC apoptosis and calcification. Conclusions: BMP-2 plays a crucial role in calcium deposition in VSMCs and VC in CKD patients via a mechanism involving the Wnt/β-catenin pathway.",
"title": "Vascular Calcification in Chronic Kidney Disease is Induced by Bone Morphogenetic Protein-2 via a Mechanism Involving the Wnt/β-Catenin Pathway"
},
{
"docid": "44030361",
"text": "Accumulated evidence suggests that an altered ambulatory blood pressure (BP) profile, particularly elevated nighttime BP, reflects target organ injury and is a better predictor of further cardiorenal risk than the clinic BP or daytime BP in hypertensive patients complicated by chronic kidney disease (CKD). In this study, we examined the beneficial effects of olmesartan, an angiotensin II type 1 receptor blocker (ARB), on ambulatory BP profiles and renal function in hypertensive CKD patients. Forty-six patients were randomly assigned to the olmesartan add-on group (n=23) or the non-ARB group (n=23). At baseline and after the 16-week treatment period, ambulatory BP monitoring was performed and renal function parameter measurements were collected. Although the baseline clinic BP levels and the after-treatment/baseline (A/B) ratios of clinic BP levels were similar in the olmesartan add-on and non-ARB groups, the A/B ratios of ambulatory 24-h and nighttime BP levels in the olmesartan add-on group were significantly lower. Furthermore, the A/B ratios of urinary protein, albumin and type IV collagen excretion in the olmesartan add-on group were significantly lower than those in the non-ARB group (urinary protein excretion, 0.72±0.41 vs. 1.45±1.48, P=0.030; urinary albumin excretion, 0.73±0.37 vs. 1.50±1.37, P=0.005; urinary type IV collagen excretion, 0.87±0.42 vs. 1.48±0.87, P=0.014) despite comparable A/B ratios for the estimated glomerular filtration rate in the two groups. These results indicate that in hypertensive patients with CKD, olmesartan add-on therapy improves the ambulatory BP profile via a preferential reduction in nighttime BP with concomitant renal injury inhibition.",
"title": "The angiotensin II type 1 receptor blocker olmesartan preferentially improves nocturnal hypertension and proteinuria in chronic kidney disease"
},
{
"docid": "23868856",
"text": "Reactive oxygen species have been linked with neuropathological changes in the central nervous system. Epidemiological studies supported the beneficial effect of supplementation of antioxidants. Superoxide dismutase (SOD) is an endogenous enzyme which can scavenge reactive oxygen species. This study investigated the effect of supplementation with ascorbic acid (vitamin C) on the changes of SOD in cultured neurological cells. Rat brain astrocytes (RBA-1 cells) were incubated with vitamin C and divided into four groups: a control group (without vitamin C) and three treatment groups with vitamin C at 40, 80, and 160 µmol/l. After short-term (2 days) and long-term (7 days) incubation, SOD activity, SOD mRNA level by Northern blotting, and SOD protein amounts by Western blotting were measured. After 2 days of incubation, vitamin C resulted in a decrease in the activity of SOD in a concentration-dependent manner (Mn-SOD from 14.8 ± 1.2 to 13.2 ± 0.5 U/mg protein and Cu/Zn-SOD from 64.8 ± 1.2 to 51.7 ± 0.9 U/mg protein; p < 0.05), and vitamin C also attenuated the Cu/Zn-SOD mRNA level from 100 to 86.3 ± 6.7%; p < 0.01), whereas the protein amounts of these two SODs remained unchanged. After 7 days of incubation with vitamin C, the SOD activity of RBA-1 cells decreased significantly (Mn-SOD from 14.9 ± 0.3 to 11.8 ± 0.3 U/mg protein and Cu/Zn SOD from 61.8 ± 1.8 to 54.6 ± 0.9 U/mg protein; p < 0.01), and the mRNA level was also attenuated (Mn-SOD from 100 to 86.8 ± 8.7% and Cu/Zn-SOD from 100 to 84.7 ± 4.8%; p < 0.01). These results suggest that 2 and 7 days of incubation with relatively high concentrations of vitamin C may downregulate activity and gene expression of SOD in cultured RBA-1 cells.",
"title": "Downregulation of Superoxide Dismutase Activity and Gene Expression in Cultured Rat Brain Astrocytes after Incubation with Vitamin C"
},
{
"docid": "195680777",
"text": "BACKGROUND Moderate differences in efficacy between adjuvant chemotherapy regimens for breast cancer are plausible, and could affect treatment choices. We sought any such differences. METHODS We undertook individual-patient-data meta-analyses of the randomised trials comparing: any taxane-plus-anthracycline-based regimen versus the same, or more, non-taxane chemotherapy (n=44,000); one anthracycline-based regimen versus another (n=7000) or versus cyclophosphamide, methotrexate, and fluorouracil (CMF; n=18,000); and polychemotherapy versus no chemotherapy (n=32,000). The scheduled dosages of these three drugs and of the anthracyclines doxorubicin (A) and epirubicin (E) were used to define standard CMF, standard 4AC, and CAF and CEF. Log-rank breast cancer mortality rate ratios (RRs) are reported. FINDINGS In trials adding four separate cycles of a taxane to a fixed anthracycline-based control regimen, extending treatment duration, breast cancer mortality was reduced (RR 0·86, SE 0·04, two-sided significance [2p]=0·0005). In trials with four such extra cycles of a taxane counterbalanced in controls by extra cycles of other cytotoxic drugs, roughly doubling non-taxane dosage, there was no significant difference (RR 0·94, SE 0·06, 2p=0·33). Trials with CMF-treated controls showed that standard 4AC and standard CMF were equivalent (RR 0·98, SE 0·05, 2p=0·67), but that anthracycline-based regimens with substantially higher cumulative dosage than standard 4AC (eg, CAF or CEF) were superior to standard CMF (RR 0·78, SE 0·06, 2p=0·0004). Trials versus no chemotherapy also suggested greater mortality reductions with CAF (RR 0·64, SE 0·09, 2p<0·0001) than with standard 4AC (RR 0·78, SE 0·09, 2p=0·01) or standard CMF (RR 0·76, SE 0·05, 2p<0·0001). In all meta-analyses involving taxane-based or anthracycline-based regimens, proportional risk reductions were little affected by age, nodal status, tumour diameter or differentiation (moderate or poor; few were well differentiated), oestrogen receptor status, or tamoxifen use. Hence, largely independently of age (up to at least 70 years) or the tumour characteristics currently available to us for the patients selected to be in these trials, some taxane-plus-anthracycline-based or higher-cumulative-dosage anthracycline-based regimens (not requiring stem cells) reduced breast cancer mortality by, on average, about one-third. 10-year overall mortality differences paralleled breast cancer mortality differences, despite taxane, anthracycline, and other toxicities. INTERPRETATION 10-year gains from a one-third breast cancer mortality reduction depend on absolute risks without chemotherapy (which, for oestrogen-receptor-positive disease, are the risks remaining with appropriate endocrine therapy). Low absolute risk implies low absolute benefit, but information was lacking about tumour gene expression markers or quantitative immunohistochemistry that might help to predict risk, chemosensitivity, or both. FUNDING Cancer Research UK; British Heart Foundation; UK Medical Research Council.",
"title": "Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials."
},
{
"docid": "42441846",
"text": "INTRODUCTION Elevated plasma total homocysteine is a major risk for coronary artery disease (CAD). Methyltetrahydrofolate reductase (MTHFR) is a main regulatory enzyme in homocysteine metabolism; a common C677T mutation in the MTHFR gene results in decreased enzyme activity, and contributes to increased homocysteine levels and decreased folate levels. We investigated the frequency of MTHFR C677T alleles in a Korean population, determined the genotype-specific threshold levels of folate or vitamin B12, and investigated the relationship between the TT genotype and the risk of CAD. MATERIALS AND METHODS We enrolled a study population of 163 CAD patients and 50 control subjects, and screened the MTHFR C677T polymorphism using real-time PCR with melting point analysis. Levels of plasma homocysteine, folate and vitamin B12 were also determined. We then defined the genotype-specific threshold values of folate and vitamin B12 required to keep homocysteine levels in a normal range for individuals of each MTHFR C677T genotype. RESULTS The frequency of the TT genotype was 18% in control subjects and 26% in patients group (P>0.05). Individuals homozygous for the TT genotype had significantly elevated homocysteine levels (P<0.05). The genotype-specific folate threshold level was significantly higher in TT individuals than in the CC or CT genotypes. The OR of individuals with low folate status and the TT genotype to estimate the relative risk of CAD was 2.2 and the OR of those with high folate status and the TT genotype was 1.5 (95% CI, 0.5-9.6 and 0.7-3.2, respectively). CONCLUSION We were able to define a gene-nutrient interaction that shows a higher risk for CAD based on specific threshold folate levels required by different MTHFR C677T genotypes in a Korean population.",
"title": "Gene--nutrition interactions in coronary artery disease: correlation between the MTHFR C677T polymorphism and folate and homocysteine status in a Korean population."
},
{
"docid": "6549091",
"text": "BACKGROUND This clinical investigation was performed to compare the effects of permanent dual-chamber cardiac pacing with pharmacological therapy in patients with recurrent vasovagal syncope. METHODS AND RESULTS Patients from 14 centers were randomized to receive either a DDD pacemaker provided with rate-drop response function or the beta-blocker atenolol at the dosage of 100 mg once a day. Inclusion criteria were age >35 years, >/=3 syncopal spells in the preceding 2 years, and positive response to tilt table testing with syncope occurring in association with relative bradycardia. The primary outcome was the first recurrence of syncope after randomization. Enrollment was started in December 1997, and the first formal interim analysis was performed on July 30, 2000. By that time, 93 patients (38 men and 55 women; mean age, 58.1+/-14.3 years) had been enrolled and randomized, although follow-up data were available for all patients (46 patients in the pacemaker arm, 47 patients in the pharmacological arm). The interim analysis showed a significant effect in favor of permanent cardiac pacing (recurrence of syncope in 2 patients [4.3%] after a median of 390 days) compared with medical treatment (recurrence of syncope in 12 patients [25.5%] after a median of 135 days; OR, 0.133; 95% CI, 0.028 to 0.632; P=0.004). Consequently, enrollment and follow-up were terminated. CONCLUSIONS DDD pacing with rate-drop response function is more effective than beta-blockade for the prevention of syncopal recurrences in highly symptomatic vasovagal fainters with relative bradycardia during tilt-induced syncope.",
"title": "Permanent cardiac pacing versus medical treatment for the prevention of recurrent vasovagal syncope: a multicenter, randomized, controlled trial."
},
{
"docid": "12232678",
"text": "Recent reports have suggested that birds lack a mechanism of wholesale dosage compensation for the Z sex chromosome. This discovery was rather unexpected, as all other animals investigated with chromosomal mechanisms of sex determination have some method to counteract the effects of gene dosage of the dominant sex chromosome in males and females. Despite the lack of a global mechanism of avian dosage compensation, the pattern of gene expression difference between males and females varies a great deal for individual Z-linked genes. This suggests that some genes may be individually dosage compensated, and that some less-than-global pattern of dosage compensation, such as local or temporal, exists on the avian Z chromosome. We used global gene expression profiling in males and females for both somatic and gonadal tissue at several time points in the life cycle of the chicken to assess the pattern of sex-biased gene expression on the Z chromosome. Average fold-change between males and females varied somewhat among tissue time-point combinations, with embryonic brain samples having the smallest gene dosage effects, and adult gonadal tissue having the largest degree of male bias. Overall, there were no neighborhoods of overall dosage compensation along the Z. Taken together, this suggests that dosage compensation is regulated on the Z chromosome entirely on a gene-by-gene level, and can vary during the life cycle and by tissue type. This regulation may be an indication of how critical a given gene's functionality is, as the expression level for essential genes will be tightly regulated in order to avoid perturbing important pathways and networks with differential expression levels in males and females.",
"title": "All dosage compensation is local: Gene-by-gene regulation of sex-biased expression on the chicken Z chromosome"
},
{
"docid": "4462079",
"text": "Recent evidence suggests that vitamin D intakes above current recommendations may be associated with better health outcomes. However, optimal serum concentrations of 25-hydroxyvitamin D [25(OH)D] have not been defined. This review summarizes evidence from studies that evaluated thresholds for serum 25(OH)D concentrations in relation to bone mineral density (BMD), lower-extremity function, dental health, and risk of falls, fractures, and colorectal cancer. For all endpoints, the most advantageous serum concentrations of 25(OH)D begin at 75 nmol/L (30 ng/mL), and the best are between 90 and 100 nmol/L (36-40 ng/mL). In most persons, these concentrations could not be reached with the currently recommended intakes of 200 and 600 IU vitamin D/d for younger and older adults, respectively. A comparison of vitamin D intakes with achieved serum concentrations of 25(OH)D for the purpose of estimating optimal intakes led us to suggest that, for bone health in younger adults and all studied outcomes in older adults, an increase in the currently recommended intake of vitamin D is warranted. An intake for all adults of > or =1000 IU (25 microg) [DOSAGE ERROR CORRECTED] vitamin D (cholecalciferol)/d is needed to bring vitamin D concentrations in no less than 50% of the population up to 75 nmol/L. The implications of higher doses for the entire adult population should be addressed in future studies.",
"title": "Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes."
},
{
"docid": "27545868",
"text": "Kidney diseases, including chronic kidney disease (CKD) and acute kidney injury (AKI), are associated with inflammation. The mechanism that regulates inflammation in these renal injuries remains unclear. Here, we demonstrated that p300/CBP-associated factor (PCAF), a histone acetyltransferase, was overexpressed in the kidneys of db/db mice and lipopolysaccharide (LPS)-injected mice. Moreover, elevated histone acetylation, such as H3K18ac, and up-regulation of some inflammatory genes, such as ICAM-1, VCAM-1, and MCP-1, were found upon these renal injuries. Furthermore, increased H3K18ac was recruited to the promoters of ICAM-1, VCAM-1, and MCP-1 in the kidneys of LPS-injected mice. In vitro studies demonstrated that PCAF knockdown in human renal proximal tubule epithelial cells (HK-2) led to downregulation of inflammatory molecules, including VCAM-1, ICAM-1, p50 subunit of NF-κB (p50), and MCP-1 mRNA and protein levels, together with significantly decreased H3K18ac level. Consistent with these, overexpression of PCAF enhanced the expression of inflammatory molecules. Furthermore, PCAF deficiency reduced palmitate-induced recruitment of H3K18ac on the promoters of ICAM-1 and MCP-1, as well as inhibited palmitate-induced upregulation of these inflammatory molecules. In summary, the present work demonstrates that PCAF plays an essential role in the regulation of inflammatory molecules through H3K18ac, which provides a potential therapeutic target for inflammation-related renal diseases.",
"title": "Histone acetyltransferase PCAF regulates inflammatory molecules in the development of renal injury."
},
{
"docid": "35724562",
"text": "In adult patients with CKD, hypertension is linked to the development of left ventricular hypertrophy, but whether this association exists in children with CKD has not been determined conclusively. To assess the relationship between BP and left ventricular hypertrophy, we prospectively analyzed data from the Chronic Kidney Disease in Children cohort. In total, 478 subjects were enrolled, and 435, 321, and 142 subjects remained enrolled at years 1, 3, and 5, respectively. Echocardiograms were obtained 1 year after study entry and then every 2 years; BP was measured annually. A linear mixed model was used to assess the effect of BP on left ventricular mass index, which was measured at three different visits, and a mixed logistic model was used to assess left ventricular hypertrophy. These models were part of a joint longitudinal and survival model to adjust for informative dropout. Predictors of left ventricular mass index included systolic BP, anemia, and use of antihypertensive medications other than angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Predictors of left ventricular hypertrophy included systolic BP, female sex, anemia, and use of other antihypertensive medications. Over 4 years, the adjusted prevalence of left ventricular hypertrophy decreased from 15.3% to 12.6% in a systolic BP model and from 15.1% to 12.6% in a diastolic BP model. These results indicate that a decline in BP may predict a decline in left ventricular hypertrophy in children with CKD and suggest additional factors that warrant additional investigation as predictors of left ventricular hypertrophy in these patients.",
"title": "BP control and left ventricular hypertrophy regression in children with CKD."
},
{
"docid": "27665523",
"text": "Oxidative stress has been increasingly linked to the high incidence of cardiovascular events in patients with chronic kidney disease (CKD), especially as traditional cardiovascular risk factors seem to not be able to account for the huge cardiovascular morbidity and mortality in this population group. Oxidative stress is increased in patients with renal impairment as a result of increased oxidant activity and reduced antioxidant capacity, and this is increased in a graded manner with increasing renal dysfunction. Inflammation, which is also present in CKD, further amplifies the oxidant generation process. The two clinical sequelae of oxidative stress are endothelial dysfunction and left ventricular hypertrophy, which have adverse cardiovascular consequences. With our new understanding of oxidative stress, it is now important to assess treatment options that reduce it in the hope that they reverse endothelial dysfunction and left ventricular hypertrophy and the clinical sequelae of these abnormalities.",
"title": "Oxidative stress in renal dysfunction: mechanisms, clinical sequelae and therapeutic options"
},
{
"docid": "8856690",
"text": "The hormonal metabolite of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25D), initiates biological responses via binding to the vitamin D receptor (VDR). When occupied by 1,25D, VDR interacts with the retinoid X receptor (RXR) to form a heterodimer that binds to vitamin D responsive elements in the region of genes directly controlled by 1,25D. By recruiting complexes of either coactivators or corepressors, ligand-activated VDR-RXR modulates the transcription of genes encoding proteins that promulgate the traditional functions of vitamin D, including signaling intestinal calcium and phosphate absorption to effect skeletal and calcium homeostasis. Thus, vitamin D action in a particular cell depends upon the metabolic production or delivery of sufficient concentrations of the 1,25D ligand, expression of adequate VDR and RXR coreceptor proteins, and cell-specific programming of transcriptional responses to regulate select genes that encode proteins that function in mediating the effects of vitamin D. For example, 1,25D induces RANKL, SPP1 (osteopontin), and BGP (osteocalcin) to govern bone mineral remodeling; TRPV6, CaBP9k, and claudin 2 to promote intestinal calcium absorption; and TRPV5, klotho, and Npt2c to regulate renal calcium and phosphate reabsorption. VDR appears to function unliganded by 1,25D in keratinocytes to drive mammalian hair cycling via regulation of genes such as CASP14, S100A8, SOSTDC1, and others affecting Wnt signaling. Finally, alternative, low-affinity, non-vitamin D VDR ligands, e.g., lithocholic acid, docosahexaenoic acid, and curcumin, have been reported. Combined alternative VDR ligand(s) and 1,25D/VDR control of gene expression may delay chronic disorders of aging such as osteoporosis, type 2 diabetes, cardiovascular disease, and cancer.",
"title": "Molecular Mechanisms of Vitamin D Action"
},
{
"docid": "8570690",
"text": "INTRODUCTION Topiramate (TOP) blocks glutamate receptors and facilitates GABA (γ-aminobutyric acid) neurotransmission, effects that may facilitate smoking cessation. We compared the effects of behavioral counseling combined with (a) TOP, (b) TOP/nicotine patch (TOP/NIC), or (c) placebo (PLC) for smoking cessation. METHODS We conducted a 10-week randomized trial in which subjects and research personnel were blinded to TOP versus PLC but not to the TOP/NIC patch condition. In groups receiving TOP, the medication dosage was titrated gradually up to 200 mg/day. The smoking quit date (QD) was scheduled after 2 weeks of medication treatment. NIC (21 mg) was started on the QD in subjects randomized to the TOP/NIC condition. The main outcome measure was the end-of-treatment, 4-week continuous abstinence rate (CAR; biochemically confirmed). RESULTS Fifty-seven subjects were randomized to treatment. The 4-week CAR was 1 of 19 (5%) in the PLC group, 5 of 19 (26%) in the TOP group, and 7 of 19 (37%) in the TOP/NIC group (p = .056). Pairwise comparisons showed a difference between TOP/NIC and PLC (p = .042) and a nonsignificant difference between TOP and PLC (p = .18). The PLC group gained 0.37 lb/week, the TOP group lost 0.41 lb/week, and the TOP/NIC group lost 0.07 lb/week (p = .004). Pairwise comparisons showed a difference between TOP and PLC (p < .001) and between TOP/NIC and PLC groups (p = .035). Paresthesia was more frequent in subjects on TOP than PLC (p = .011). CONCLUSIONS TOP, alone or in combination with the NIC, resulted in a numerically higher quit rate than PLC and decreased weight. A larger, PLC-controlled trial is needed to confirm these findings.",
"title": "Topiramate for smoking cessation: a randomized, placebo-controlled pilot study."
},
{
"docid": "30720103",
"text": "Vitamin D, the sunshine vitamin, is now recognized not only for its importance in promoting bone health in children and adults but also for other health benefits, including reducing the risk of chronic diseases such as autoimmune diseases, common cancer, and cardiovascular disease. Vitamin D made in the skin or ingested in the diet is biologically inert and requires 2 successive hydroxylations first in the liver on carbon 25 to form 25-hydroxyvitamin D [25(OH)D], and then in the kidney for a hydroxylation on carbon 1 to form the biologically active form of vitamin D, 1,25-dihydroxyvitamin D [1,25(OH)(2)D]. With the identification of 25(OH)D and 1,25(OH)(2)D, methods were developed to measure these metabolites in the circulation. Serum 25(OH)D is the barometer for vitamin D status. Serum 1,25(OH)(2)D provides no information about vitamin D status and is often normal or even increased as the result of secondary hyperparathyroidism associated with vitamin D deficiency. Most experts agree that 25(OH)D of <20 ng/mL is considered to be vitamin D deficiency, whereas a 25(OH)D of 21-29 ng/mL is considered to be insufficient. The goal should be to maintain both children and adults at a level >30 ng/mL to take full advantage of all the health benefits that vitamin D provides.",
"title": "Vitamin D status: measurement, interpretation, and clinical application."
},
{
"docid": "40971746",
"text": "Intensive study of a few genetically tractable species with XX/XY sex chromosomes has produced generalizations about the process of sex chromosome dosage compensation that do not fare well when applied to ZZ/ZW sex chromosome systems, such as those in birds. The inherent sexual imbalance in dose of sex chromosome genes has led to the evolution of sex-chromosome-wide mechanisms for balancing gene dosage between the sexes and relative to autosomal genes. Recent advances in our knowledge of avian genomes have led to a reexamination of sex-specific dosage compensation (SSDC) in birds, which is less effective than in known XX/XY systems. Insights about the mechanisms of SSDC in birds also suggest similarities to and differences from those in XX/XY species. Birds are thus offering new opportunities for studying dosage compensation in a ZZ/ZW system, which should shed light on the evolution of SSDC more broadly.",
"title": "A bird's-eye view of sex chromosome dosage compensation."
},
{
"docid": "16252863",
"text": "The list of preventable and reversible risk factors for atherosclerotic cardiovascular disease continues to grow. Cigarette smoking, high blood pressure, physical inactivity, elevated cholesterol, underlying lipoprotein abnormalities, lipoprotein(a), diabetes, overweight, male gender, and age are well-established risk factors. During the 1990s, there have been many reports associating elevated plasma homocysteine levels with arteriosclerotic cardiovascular disease and consistent evidence that dietary and supplemental folic acid can reduce homocysteine levels.1 2 The article by Robinson and colleagues3 in this issue of Circulation presents further evidence of the importance of homocysteine and suggestive evidence that plasma folate and plasma pyrixodal-l-phosphate (vitamin B6) are protective factors. Their study is part of the European Concerted Action Project,4 which examined 750 patients younger than age 60 with diagnoses within the previous 12 months of coronary, cerebrovascular, or peripheral vascular disease and 800 healthy control subjects. The patient groups were young (47 years for cases and 44 years for control subjects) and heterogeneous, with nonfatal clinical events or symptoms of arteriosclerotic cardiovascular disease supported by ECG, angiographic, or Doppler evidence; the study involved 19 centers in nine European countries. Men in the highest quintile for fasting total homocysteine (tHcy), compared with the remainder of the population, had an estimated relative risk of 2.2 (95% confidence interval [CI], 1.6 to 2.9), with a striking dose-response relationship and a more-than-multiplicative interaction with cigarette smoking and high blood pressure on vascular disease risk4 ; the corresponding estimated relative risk for coronary heart disease was similar (2.0; 95% CI 1.6 to 2.8). (tHcy is the sum of homocysteine and homocysteinyl moieties of oxidized disulfides, homocystine, and cysteine- homocysteine. ) Robinson and colleagues3 examined three B vitamins in detail to determine their effects on fasting and post–methionine-loading tHcy levels and any independent effects on cardiovascular disease …",
"title": "Preventing coronary heart disease: B vitamins and homocysteine."
},
{
"docid": "35149431",
"text": "Two synthetic peripheral nerve myelin P0 protein peptides, an immunodominant (amino acids 180-199) and a cryptic (amino acids 56-71) one, induced an acute or chronic course of experimental autoimmune neuritis (EAN) in Lewis rats, when given at low dose (50-100 microg/rat) or high dose (250 microg/rat), respectively. Corresponding to the different clinical course, pathological changes and immune responses were found: (1) Onset of clinical signs of P0 peptide 56-71 (P0 56-71) induced EAN was 1-3 days later than in P0 peptide 180-199 (P0 180-199) induced EAN at all immunizing doses, whereas the peak of the disease occurred at a similar time point post immunization (p.i.), i.e. at days 14-16 p.i. in P0 56-71 induced EAN and at day 16 p.i. in P0 180-199 induced EAN. (2) Intramolecular epitope spreading as assessed by delayed type hypersensitivity response occurred in P0 56-71 induced EAN at both low and high antigen doses and in P0 180-199 induced EAN at high antigen dose (250 microg/rat) only. (3) P0 180-199 stimulated higher levels of interferon-gamma production in P0 180-199 induced EAN than in P0 56-71 induced EAN and vice versa. (4) Histopathologic evaluation revealed a similar grade of mononuclear cell infiltration in the sciatic nerves of both types of EAN, but more severe demyelination was found in P0 180-199 induced EAN compared to P0 56-71 induced EAN. The results support the hypothesis that high dose autoantigen immunization induces extensive determinant spreading and chronic course of autoimmune diseases.",
"title": "P0 glycoprotein peptides 56–71 and 180–199 dose-dependently induce acute and chronic experimental autoimmune neuritis in Lewis rats associated with epitope spreading"
},
{
"docid": "23581096",
"text": "The SRY gene on the mammalian Y chromosome undoubtedly acts to determine testis, but it is still quite unclear how. It was originally supposed that SRY acts directly to activate other genes in the testis-determining pathway. This paper presents an alternative hypothesis that SRY functions indirectly, by interacting with related genes SOX3 (from which SRY evolved) and SOX9 (which appears to be intimately involved in vertebrate gonad differentiation). Specifically, I propose that in females SOX3 inhibits SOX9 function, but in males, SRY inhibits SOX3 and permits SOX9 to enact its testis-determining role. This hypothesis makes testable predictions of the phenotypes of XX and XY individuals with deficiencies or overproduction of any of the three genes, and is able to account for the difficult cases of XX(SRY-) males and transdifferentiation in the absence of SRY. The hypothesis also suggests a way that the dominant SRY sex-determining system of present-day mammals may have evolved from an ancient system relying on SOX3 dosage.",
"title": "Interactions between SRY and SOX genes in mammalian sex determination."
},
{
"docid": "40790033",
"text": "BACKGROUND The Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial showed that initial antihypertensive therapy with benazepril plus amlodipine was superior to benazepril plus hydrochlorothiazide in reducing cardiovascular morbidity and mortality. We assessed the effects of these drug combinations on progression of chronic kidney disease. METHODS ACCOMPLISH was a double-blind, randomised trial undertaken in five countries (USA, Sweden, Norway, Denmark, and Finland). 11 506 patients with hypertension who were at high risk for cardiovascular events were randomly assigned via a central, telephone-based interactive voice response system in a 1:1 ratio to receive benazepril (20 mg) plus amlodipine (5 mg; n=5744) or benazepril (20 mg) plus hydrochlorothiazide (12.5 mg; n=5762), orally once daily. Drug doses were force-titrated for patients to attain recommended blood pressure goals. Progression of chronic kidney disease, a prespecified endpoint, was defined as doubling of serum creatinine concentration or end-stage renal disease (estimated glomerular filtration rate <15 mL/min/1.73 m(2) or need for dialysis). Analysis was by intention to treat (ITT). This trial is registered with ClinicalTrials.gov, number NCT00170950. FINDINGS The trial was terminated early (mean follow-up 2.9 years [SD 0.4]) because of superior efficacy of benazepril plus amlodipine compared with benazepril plus hydrochlorothiazide. At trial completion, vital status was not known for 143 (1%) patients who were lost to follow-up (benazepril plus amlodipine, n=70; benazepril plus hydrochlorothiazide, n=73). All randomised patients were included in the ITT analysis. There were 113 (2.0%) events of chronic kidney disease progression in the benazepril plus amlodipine group compared with 215 (3.7%) in the benazepril plus hydrochlorothiazide group (HR 0.52, 0.41-0.65, p<0.0001). The most frequent adverse event in patients with chronic kidney disease was peripheral oedema (benazepril plus amlodipine, 189 of 561, 33.7%; benazepril plus hydrochlorothiazide, 85 of 532, 16.0%). In patients with chronic kidney disease, angio-oedema was more frequent in the benazepril plus amlodipine group than in the benazepril plus hydrochlorothiazide group. In patients without chronic kidney disease, dizziness, hypokalaemia, and hypotension were more frequent in the benazepril plus hydrochlorothiazide group than in the benazepril plus amlodipine group. INTERPRETATION Initial antihypertensive treatment with benazepril plus amlodipine should be considered in preference to benazepril plus hydrochlorothiazide since it slows progression of nephropathy to a greater extent. FUNDING Novartis.",
"title": "Renal outcomes with different fixed-dose combination therapies in patients with hypertension at high risk for cardiovascular events (ACCOMPLISH): a prespecified secondary analysis of a randomised controlled trial."
},
{
"docid": "19278208",
"text": "Background/Objectives:Folic acid supplementation has been suggested to reduce the risk of preeclampsia. However, results from few epidemiologic studies have been inconclusive. We investigated the hypothesis that folic acid supplementation and dietary folate intake before conception and during pregnancy reduce the risk of preeclampsia. Subjects/Methods:A birth cohort study was conducted in 2010–2012 at the Gansu Provincial Maternity & Child Care Hospital in Lanzhou, China. A total of 10 041 pregnant women without chronic hypertension or gestational hypertension were enrolled. Results:Compared with nonusers, folic acid supplement users had a reduced risk of preeclampsia (OR=0.61, 95% CI: 0.43–0.87). A significant dose–response of duration of use was observed among women who used folic acid supplemention during pregnancy only (P-trend=0.007). The reduced risk associated with folic acid supplement was similar for mild or severe preeclampsia and for early- or late-onset preeclampsia, although the statistical significant associations were only observed for mild (OR=0.50, 95% CI: 0.30–0.81) and late-onset (OR=0.60, 95% CI: 0.42–0.86) preeclampsia. The reduced risk associated with dietary folate intake during pregnancy was only seen for severe preeclampsia (OR=0.52, 95% CI: 0.31–0.87, for the highest quartile of dietary folate intake compared with the lowest).Conclusions:Our study results suggest that folic acid supplementation and higher dietary folate intake during pregnancy reduce the risk of preeclampsia. Future studies are needed to confirm the associations.",
"title": "Folic acid supplementation and dietary folate intake, and risk of preeclampsia"
},
{
"docid": "12810152",
"text": "CONTEXT Hyperhomocysteinemia is caused by genetic and lifestyle influences, including low intakes of folate and vitamin B6. However, prospective data relating intake of these vitamins to risk of coronary heart disease (CHD) are not available. OBJECTIVE To examine intakes of folate and vitamin B6 in relation to the incidence of nonfatal myocardial infarction (MI) and fatal CHD. DESIGN Prospective cohort study. SETTING AND PATIENTS In 1980, a total of 80082 women from the Nurses' Health Study with no previous history of cardiovascular disease, cancer, hypercholesterolemia, or diabetes completed a detailed food frequency questionnaire from which we derived usual intake of folate and vitamin B6. MAIN OUTCOME MEASURE Nonfatal MI and fatal CHD confirmed by World Health Organization criteria. RESULTS During 14 years of follow-up, we documented 658 incident cases of nonfatal MI and 281 cases of fatal CHD. After controlling for cardiovascular risk factors, including smoking and hypertension and intake of alcohol, fiber, vitamin E, and saturated, polyunsaturated, and trans fat, the relative risks (RRs) of CHD between extreme quintiles were 0.69 (95% confidence interval [CI], 0.55-0.87) for folate (median intake, 696 microg/d vs 158 microg/d) and 0.67 (95% CI, 0.53-0.85) for vitamin B6 (median intake, 4.6 mg/d vs 1.1 mg/d). Controlling for the same variables, the RR was 0.55 (95% CI, 0.41-0.74) among women in the highest quintile of both folate and vitamin B6 intake compared with the opposite extreme. Risk of CHD was reduced among women who regularly used multiple vitamins (RR=0.76; 95% CI, 0.65-0.90), the major source of folate and vitamin B6, and after excluding multiple vitamin users, among those with higher dietary intakes of folate and vitamin B6. In a subgroup analysis, compared with nondrinkers, the inverse association between a high-folate diet and CHD was strongest among women who consumed up to 1 alcoholic beverage per day (RR =0.69; 95% CI, 0.49-0.97) or more than 1 drink per day (RR=0.27; 95% CI, 0.13-0.58). CONCLUSION These results suggest that intake of folate and vitamin B6 above the current recommended dietary allowance may be important in the primary prevention of CHD among women.",
"title": "Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women."
}
] |
498
|
Having a main partner worsens HIV outcomes.
|
[
{
"docid": "17077004",
"text": "OBJECTIVES To explore the association between a stable partnership and clinical outcome in HIV infected patients receiving highly active antiretroviral therapy (HAART). DESIGN Prospective cohort study of adults with HIV (Swiss HIV cohort study). SETTING Seven outpatient clinics throughout Switzerland. PARTICIPANTS The 3736 patients in the cohort who started HAART before 2002 (median age 36 years, 29% female, median follow up 3.6 years). MAIN OUTCOME MEASURES Time to AIDS or death (primary endpoint), death alone, increases in CD4 cell count of at least 50 and 100 above baseline, optimal viral suppression (a viral load below 400 copies/ml), and viral rebound. RESULTS During follow up 2985 (80%) participants reported a stable partnership on at least one occasion. When starting HAART, 52% (545/1042) of participants reported a stable partnership; after five years of follow up 46% (190/412) of participants reported a stable partnership. In an analysis stratified by previous antiretroviral therapy and clinical stage when starting HAART (US Centers for Disease Control and Prevention group A, B, or C), the adjusted hazard ratio for progression to AIDS or death was 0.79 (95% confidence interval 0.63 to 0.98) for participants with a stable partnership compared with those without. Adjusted hazards ratios for other endpoints were 0.59 (0.44 to 0.79) for progression to death, 1.15 (1.06 to 1.24) for an increase in CD4 cells of 100 counts/microl or more, and 1.06 (0.98 to 1.14) for optimal viral suppression. CONCLUSIONS A stable partnership is associated with a slower rate of progression to AIDS or death in HIV infected patients receiving HAART.",
"title": "Stable partnership and progression to AIDS or death in HIV infected patients receiving highly active antiretroviral therapy: Swiss HIV cohort study."
}
] |
[
{
"docid": "5835149",
"text": "OBJECTIVE To determine the prevalence and risk factors for hepatitis C virus (HCV) infection in a cohort of homosexually active men, with particular reference to assessing sexual transmission. DESIGN Prevalence based on cross-sectional testing for HCV (c100 protein) antibody in a cohort using sera stored between 1984 and 1989, and assessment of risk factors using a case-control analysis based on questionnaire data from HCV positive and negative subjects. SUBJECTS/SETTING 1038 homosexually active men who were participating in a prospective study established to identify risk factors for AIDS. They had been recruited through private and public primary care and sexually transmissible disease (STD) services in central Sydney. MAIN OUTCOME MEASURES Prevalence of HCV antibody and its association with human immunodeficiency virus type 1 (HIV-1) infection and other STDs, number of sexual partners, sexual practices and recreational drug use. RESULTS Overall, 7.6% of subjects tested were seropositive for HCV antibody. In univariate analysis, HCV infection was significantly associated with injecting drug use (IDU) (OR = 8.18, p < 0.0001) and HIV infection (OR = 3.14, p < 0.0001) and with self reported history of syphilis (OR = 1.88, p = 0.016), anogenital herpes (OR = 1.93, p = 0.017), gonorrhoea (OR = 2.43, p = 0.009) and hepatitis B (OR = 1.92, p = 0.010). In case control analysis, similar sexual behaviours (partner numbers and practices) were reported by HCV positive and HCV negative subjects except that HCV negative subjects more frequently reported engaging than HCV positive subject in unprotected receptive anal intercourse without ejaculation (OR = 0.61, p = 0.034), unprotected insertive (OR = 0.59, p = 0.039) and receptive (OR = 0.56, p = 0.016) oro-anal intercourse (rimming) and insertive fisting (OR = 0.48, p = 0.034). In multiple logistic regression analyses, only HIV-1 infection (OR = 3.18, p < 0.0001) and IDU in the previous six months (OR = 7.24, p < 0.0001) remained significantly associated with the presence of HCV antibody. CONCLUSIONS IDU was the major behavioural risk factor for HCV infection. If sexual or another from of transmission did occur, it may have been facilitated by concurrent HIV-1 infection.",
"title": "Hepatitis C virus infection in a large cohort of homosexually active men: independent associations with HIV-1 infection and injecting drug use but not sexual behaviour."
},
{
"docid": "5548081",
"text": "CONTEXT Some studies have inferred that an epidemic of Kaposi sarcoma-associated herpesvirus (KSHV) infection in homosexual men in the United States occurred concurrently with that of human immunodeficiency virus (HIV), but there have been no direct measurements of KSHV prevalence at the beginning of the HIV epidemic. OBJECTIVES To determine the prevalence of KSHV infection in homosexual men in San Francisco, Calif, at the beginning of the HIV epidemic in 1978 and 1979 and to examine changes in prevalence of KSHV at time points from 1978 through 1996 in light of changes in sexual behavior. DESIGN, SETTING, AND PARTICIPANTS Analysis of a clinic-based sample (n = 398) derived from the San Francisco City Clinic Cohort (ages 18-66 years) (n = 2666 for analyses herein) and from population-based samples from the San Francisco Men's Health Study (MHS) (ages 25-54 years) (n = 825 and 252) and the San Francisco Young Men's Health Study (YMHS) (ages 18-29 years) (n = 428-976, and 557); behavioral studies were longitudinal and KSHV prevalence studies were cross-sectional. MAIN OUTCOME MEASURES Antibodies against KSHV and HIV; sexual behaviors. RESULTS The prevalence of KSHV infection in 1978 and 1979 was 26.5% of 235 (a random sample) overall (weighted for HIV infection) vs 6.9% (128/1842) for HIV in the San Francisco City Clinic Cohort sample. The prevalence of KSHV infection remained essentially unchanged between an MHS sample of 252 in 1984 and 1985 (29.6%) and a YMHS sample of 557 in 1995 and 1996 (26.4%), while HIV prevalence dropped from 49.5% of 825 in 1984 and 1985 (MHS) to 17.6% of 428 in 1992 and 1993 (YMHS). The proportion of men practicing unprotected receptive anal intercourse with 1 or more partners declined from 54% to 11% during the 1984 through 1993 period (MHS) with similar though slightly higher values in the YMHS in 1992 and 1993; whereas for unprotected oral intercourse it ranged between 60% and 90% in the 1984 through 1996 period (MHS and YMHS). CONCLUSIONS Infection with KSHV was already highly prevalent in homosexual men when the HIV epidemic began in San Francisco, and its prevalence has been maintained at a nearly constant level. Any declines in the incidence of Kaposi sarcoma do not appear to be caused by a decline in KSHV transmission.",
"title": "Prevalence of Kaposi sarcoma-associated herpesvirus infection in homosexual men at beginning of and during the HIV epidemic."
},
{
"docid": "34139429",
"text": "CONTEXT Although beta-blockers improve symptoms and survival in adults with heart failure, little is known about these medications in children and adolescents. OBJECTIVE To prospectively evaluate the effects of carvedilol in children and adolescents with symptomatic systemic ventricular systolic dysfunction. DESIGN, SETTING, AND PARTICIPANTS A multicenter, randomized, double-blind, placebo-controlled study of 161 children and adolescents with symptomatic systolic heart failure from 26 US centers. In addition to treatment with conventional heart failure medications, patients were assigned to receive placebo or carvedilol. Enrollment began in June 2000 and the last dose was given in May 2005 (each patient received medication for 8 months). INTERVENTIONS Patients were randomized in a 1:1:1 ratio to twice-daily dosing with placebo, low-dose carvedilol (0.2 mg/kg per dose if weight <62.5 kg or 12.5 mg per dose if weight > or =62.5 kg), or high-dose carvedilol (0.4 mg/kg per dose if weight <62.5 kg or 25 mg per dose if weight > or =62.5 kg) and were stratified according to whether each patient's systemic ventricle was a left ventricle or not. MAIN OUTCOME MEASURES The primary outcome was a composite measure of heart failure outcomes in patients receiving carvedilol (low- and high-dose combined) vs placebo. Secondary efficacy variables included individual components of this composite, echocardiographic measures, and plasma b-type natriuretic peptide levels. RESULTS There was no statistically significant difference between groups for the composite end point based on the percentage of patients who improved, worsened, or were unchanged. Among 54 patients assigned to placebo, 30 improved (56%), 16 worsened (30%), and 8 were unchanged (15%); among 103 patients assigned to carvedilol, 58 improved (56%), 25 worsened (24%), and 20 were unchanged (19%). The rates of worsening were lower than expected. The odds ratio for worsened outcome for patients in the combined carvedilol group vs the placebo group was 0.79 (95% CI, 0.36-1.59; P = .47). A prespecified subgroup analysis noted significant interaction between treatment and ventricular morphology (P = .02), indicating a possible differential effect of treatment between patients with a systemic left ventricle (beneficial trend) and those whose systemic ventricle was not a left ventricle (nonbeneficial trend). CONCLUSIONS These preliminary results suggest that carvedilol does not significantly improve clinical heart failure outcomes in children and adolescents with symptomatic systolic heart failure. However, given the lower than expected event rates, the trial may have been underpowered. There may be a differential effect of carvedilol in children and adolescents based on ventricular morphology. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00052026.",
"title": "Carvedilol for children and adolescents with heart failure: a randomized controlled trial."
},
{
"docid": "22227889",
"text": "This study examines factors associated with caregiver burden in 82 HIV-positive (HIV+) and 162 HIV-negative (HIV-) partners of men with AIDS. We expected HIV+ caregivers to report more burden than HIV- caregivers because of the toll of their disease on their resources. HIV+ caregivers did report more burden and, compared with the HIV- caregivers, they were more religious or spiritual, had less income, and coped by using more positive reappraisal and cognitive escape-avoidance and by seeking social support. Comparisons of HIV+ caregivers with 61 HIV+ partners of healthy men indicated that most differences between HIV+ and HIV- caregivers were associated with HIV seropositivity rather than caregiving. However, of the variables associated with HIV seropositivity, only religiosity or spirituality contributed independently to burden in HIV+ caregivers, suggesting a relatively weak link between HIV seropositivity and caregiver burden. The model explained 62% of the variance in burden in HIV+ caregivers and 36% of the variance in HIV- caregivers.",
"title": "Caregiver burden in HIV-positive and HIV-negative partners of men with AIDS."
},
{
"docid": "21479231",
"text": "RATIONALE The outcome of fully intermittent thrice-weekly antituberculosis treatment of various durations in HIV-associated tuberculosis is unclear. OBJECTIVES To compare the efficacy of an intermittent 6-month regimen (Reg6M: 2EHRZ(3)/4HR(3) [ethambutol, 1,200 mg; isoniazid, 600 mg; rifampicin, 450 or 600 mg depending on body weight <60 or > or =60 kg; and pyrazinamide, 1,500 mg for 2 mo; followed by 4 mo of isoniazid and rifampicin at the same doses]) versus a 9-month regimen (Reg9M: 2EHRZ(3)/7HR(3)) in HIV/tuberculosis (TB). METHODS HIV-infected patients with newly diagnosed pulmonary or extrapulmonary TB were randomly assigned to Reg6M (n = 167) or Reg9M (n = 160) and monitored by determination of clinical, immunological, and bacteriological parameters for 36 months. Primary outcomes included favorable responses at the end of treatment and recurrences during follow-up, whereas the secondary outcome was death. Intent-to-treat and on-treatment analyses were performed. All patients were antiretroviral treatment-naive during treatment. MEASUREMENTS AND MAIN RESULTS Of the patients, 70% had culture-positive pulmonary TB; the median viral load was 155,000 copies/ml and the CD4(+) cell count was 160 cells/mm(3). Favorable response to antituberculosis treatment was similar by intent to treat (Reg6M, 83% and Reg9M, 76%; P = not significant). Bacteriological recurrences occurred significantly more often in Reg6M than in Reg9M (15 vs. 7%; P < 0.05) although overall recurrences were not significantly different (Reg6M, 19% vs. Reg9M, 13%). By 36 months, 36% of patients undergoing Reg6M and 35% undergoing Reg9M had died, with no significant difference between regimens. All 19 patients who failed treatment developed acquired rifamycin resistance (ARR), the main risk factor being baseline isoniazid resistance. CONCLUSIONS Among antiretroviral treatment-naive HIV-infected patients with TB, a 9-month regimen resulted in a similar outcome at the end of treatment but a significantly lower bacteriological recurrence rate compared with a 6-month thrice-weekly regimen. ARR was high with these intermittent regimens and neither mortality nor ARR was altered by lengthening TB treatment. Clinical Trials Registry Information: ID# NCT00376012 registered at www.clinicaltrials.gov.",
"title": "Efficacy of a 6-month versus 9-month intermittent treatment regimen in HIV-infected patients with tuberculosis: a randomized clinical trial."
},
{
"docid": "13906581",
"text": "Background Extensive debate exists in the healthcare community over whether outcomes of medical care at teaching hospitals and other healthcare units are better or worse than those at the respective nonteaching ones. Thus, our goal was to systematically evaluate the evidence pertaining to this question. Methods and Findings We reviewed all studies that compared teaching versus nonteaching healthcare structures for mortality or any other patient outcome, regardless of health condition. Studies were retrieved from PubMed, contact with experts, and literature cross-referencing. Data were extracted on setting, patients, data sources, author affiliations, definition of compared groups, types of diagnoses considered, adjusting covariates, and estimates of effect for mortality and for each other outcome. Overall, 132 eligible studies were identified, including 93 on mortality and 61 on other eligible outcomes (22 addressed both). Synthesis of the available adjusted estimates on mortality yielded a summary relative risk of 0.96 (95% confidence interval [CI], 0.93–1.00) for teaching versus nonteaching healthcare structures and 1.04 (95% CI, 0.99–1.10) for minor teaching versus nonteaching ones. There was considerable heterogeneity between studies (I2 = 72% for the main analysis). Results were similar in studies using clinical and those using administrative databases. No differences were seen in the 14 studies fully adjusting for volume/experience, severity, and comorbidity (relative risk 1.01). Smaller studies did not differ in their results from larger studies. Differences were seen for some diagnoses (e.g., significantly better survival for breast cancer and cerebrovascular accidents in teaching hospitals and significantly better survival from cholecystectomy in nonteaching hospitals), but these were small in magnitude. Other outcomes were diverse, but typically teaching healthcare structures did not do better than nonteaching ones. Conclusions The available data are limited by their nonrandomized design, but overall they do not suggest that a healthcare facility's teaching status on its own markedly improves or worsens patient outcomes. Differences for specific diseases cannot be excluded, but are likely to be small.",
"title": "Patient Outcomes with Teaching Versus Nonteaching Healthcare: A Systematic Review"
},
{
"docid": "31562330",
"text": "BACKGROUND The increased caloric requirements of HIV-positive individuals, undesirable side effects of treatment that may be worsened by malnutrition (but alleviated by nutritional support), and associated declines in adherence and possible increased drug resistance are all justifications for developing better interventions to strengthen the nutrition security of individuals receiving antiretroviral treatment. OBJECTIVE To highlight key benefits and challenges relating to interventions aimed at strengthening the nutrition security of people living with HIV who are receiving antiretroviral treatment. METHODS Qualitative research was undertaken on a short-term nutrition intervention linked to the provision of free antiretroviral treatment for people living with HIV in western Kenya in late 2005 and early 2006. RESULTS Patients enrolled in the food program while on treatment regimens self-reported greater adherence to their medication, fewer side effects, and a greater ability to satisfy increased appetite. Most clients self-reported weight gain, recovery of physical strength, and the resumption of labor activities while enrolled in dual (food supplementation and treatment) programs. Such improvements were seen to catalyze increased support from family and community. CONCLUSIONS These findings provide further empirical support to calls for a more holistic and comprehensive response to the coexistence of AIDS epidemics with chronic nutrition insecurity. Future work is needed to clarify ways of bridging the gap between short-term nutritional support to individuals and longer-term livelihood security programming for communities affected by AIDS. Such interdisciplinary research will need to be matched by intersectoral action on the part of the agriculture and health sectors in such environments.",
"title": "Integrating nutrition security with treatment of people living with HIV: lessons from Kenya."
},
{
"docid": "5850219",
"text": "BACKGROUND Population-based estimates of prevalence, risk distribution, and intervention uptake inform delivery of control programmes for sexually transmitted infections (STIs). We undertook the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3) after implementation of national sexual health strategies, and describe the epidemiology of four STIs in Britain (England, Scotland, and Wales) and the uptake of interventions. METHODS Between Sept 6, 2010 and Aug 31, 2012 , we did a probability sample survey of 15,162 women and men aged 16-74 years in Britain. Participants were interviewed with computer-assisted face-to-face and self-completion questionnaires. Urine from a sample of participants aged 16-44 years who reported at least one sexual partner over the lifetime was tested for the presence of Chlamydia trachomatis, type-specific human papillomavirus (HPV), Neisseria gonorrhoeae, and HIV antibody. We describe age-specific and sex-specific prevalences of infection and intervention uptake, in relation to demographic and behavioural factors, and explore changes since Natsal-1 (1990-91) and Natsal-2 (1999-2001). FINDINGS Of 8047 eligible participants invited to provide a urine sample, 4828 (60%) agreed. We excluded 278 samples, leaving 4550 (94%) participants with STI test results. Chlamydia prevalence was 1·5% (95% CI 1·1-2·0) in women and 1·1% (0·7-1·6) in men. Prevalences in individuals aged 16-24 years were 3·1% (2·2-4·3) in women and 2·3% (1·5-3·4) in men. Area-level deprivation and higher numbers of partners, especially without use of condoms, were risk factors. However, 60·4% (45·5-73·7) of chlamydia in women and 43·3% (25·9-62·5) in men was in individuals who had had one partner in the past year. Among sexually active 16-24-year-olds, 54·2% (51·4-56·9) of women and 34·6% (31·8-37·4) of men reported testing for chlamydia in the past year, with testing higher in those with more partners. High-risk HPV was detected in 15·9% (14·4-17·5) of women, similar to in Natsal-2. Coverage of HPV catch-up vaccination was 61·5% (58·2-64·7). Prevalence of HPV types 16 and 18 in women aged 18-20 years was lower in Natsal-3 than Natsal-2 (5·8% [3·9-8·6] vs 11·3% [6·8-18·2]; age-adjusted odds ratio 0·44 [0·21-0·94]). Gonorrhoea (<0·1% prevalence in women and men) and HIV (0·1% prevalence in women and 0·2% in men) were uncommon and restricted to participants with recognised high-risk factors. Since Natsal-2, substantial increases were noted in attendance at sexual health clinics (from 6·7% to 21·4% in women and from 7·7% to 19·6% in men) and HIV testing (from 8·7% to 27·6% in women and from 9·2% to 16·9% in men) in the past 5 years. INTERPRETATION STIs were distributed heterogeneously, requiring general and infection-specific interventions. Increases in testing and attendance at sexual health clinics, especially in people at highest risk, are encouraging. However, STIs persist both in individuals accessing and those not accessing services. Our findings provide empirical evidence to inform future sexual health interventions and services. FUNDING Grants from the UK Medical Research Council and the Wellcome Trust, with support from the Economic and Social Research Council and the Department of Health.",
"title": "Prevalence, risk factors, and uptake of interventions for sexually transmitted infections in Britain: findings from the National Surveys of Sexual Attitudes and Lifestyles (Natsal)"
},
{
"docid": "3413083",
"text": "BACKGROUND Following widespread rollout of chlamydia testing to non-specialist and community settings in the UK, many individuals receive a chlamydia test without being offered comprehensive STI and HIV testing. We assess sexual behaviour among testers in different settings with a view to understanding their need for other STI diagnostic services. METHODS A probability sample survey of the British population undertaken 2010-2012 (the third National Survey of Sexual Attitudes and Lifestyles). We analysed weighted data on chlamydia testing (past year), including location of most recent test, and diagnoses (past 5 years) from individuals aged 16-44 years reporting at least one sexual partner in the past year (4992 women, 3406 men). RESULTS Of the 26.8% (95% CI 25.4% to 28.2%) of women and 16.7% (15.5% to 18.1%) of men reporting a chlamydia test in the past year, 28.4% of women and 41.2% of men had tested in genitourinary medicine (GUM), 41.1% and 20.7% of women and men respectively tested in general practice (GP) and the remainder tested in other non-GUM settings. Women tested outside GUM were more likely to be older, in a relationship and to live in rural areas. Individuals tested outside GUM reported fewer risk behaviours; nevertheless, 11.0% (8.6% to 14.1%) of women and 6.8% (3.9% to 11.6%) of men tested in GP and 13.2% (10.2% to 16.8%) and 9.6% (6.5% to 13.8%) of women and men tested in other non-GUM settings reported 'unsafe sex', defined as two or more partners and no condom use with any partner in the past year. Individuals treated for chlamydia outside GUM in the past 5 years were less likely to report an HIV test in that time frame (women: 54.5% (42.7% to 65.7%) vs 74.1% (65.9% to 80.9%) in GUM; men: 23.9% (12.7% to 40.5%) vs 65.8% (56.2% to 74.3%)). CONCLUSIONS Most chlamydia testing occurred in non-GUM settings, among populations reporting fewer risk behaviours. However, there is a need to provide pathways to comprehensive STI care to the sizeable minority at higher risk.",
"title": "Patterns of chlamydia testing in different settings and implications for wider STI diagnosis and care: a probability sample survey of the British population"
},
{
"docid": "21216726",
"text": "Little is known about the epidemiology of human herpesvirus 8 (HHV-8) infections among women. A cross-sectional study was conducted of HHV-8 infection among human immunodeficiency virus (HIV)-infected and high-risk HIV-uninfected women. Serological tests with noninduced (latent) and induced (lytic) HHV-8 antigens were used to detect infection among 2483 participants of a multisite cohort. Reactivity to latent antigen was present in 4.1% and to induced antigens in 12.0% of women. Seven of 8 women who reported Kaposi's sarcoma had HHV-8 antibodies. Among HIV-positive women, HHV-8 infection was associated with use of crack, cocaine, or heroin (76% vs. 65%; P<.001), past syphilis (29% vs. 20%; P<.001), an injection drug-using male sex partner (61% vs. 53%; P=.014), black race (P=.010), and enrollment site (P=.015). In multivariate analysis, HIV infection, older age, past syphilis, black race, and enrollment site were independently associated with HHV-8 infection. In this cohort of North American women, HHV-8 infection was associated with HIV infection, drug use, and risky sexual behavior.",
"title": "Human herpesvirus 8 infection and Kaposi's sarcoma among human immunodeficiency virus-infected and -uninfected women."
},
{
"docid": "22414304",
"text": "There is little information about treatment outcome in patients with smear-negative pulmonary tuberculosis (PTB) or extrapulmonary tuberculosis (EPTB) treated under routine programme conditions in subsaharan Africa. A prospective study was carried out to determine treatment outcome in an unselected cohort of TB patients admitted to Zomba General Hospital, Malawi. Eight hundred and twenty-seven adult TB patients (451 men and 376 women) were registered between 1 July and 31 December 1995. Standardized treatment outcomes of treatment completion, death, default, and transfer to another district were assessed in relation to type of TB, human immunodeficiency virus (HIV) serostatus, age and gender. Two hundred and fifty-four patients (31%) died by the end of treatment, half of the deaths occurring in the first month. Death rates were 19% among 386 patients with smear-positive PTB, 46% among 211 patients with smear-negative PTB, and 37% among 230 patients with EPTB; 77% of the patients were HIV seropositive. Among new patients, HIV-positive patients had higher death rates than HIV-negative patients (hazard ratio [HR] 2.5; 95% confidence interval [95% CI] 1.6-3.8). Smear-negative patients had the highest death rates (HR 3.9; 95% CI 2.7-5.5 compared to smear-positive patients), followed by EPTB patients (HR 2.6, 95% CI 1.8-3.7 compared to smear-positive patients). Death rates increased with age but were similar in men and women. Adult patients in Malawi with smear-negative PTB and EPTB have low treatment completion and high death rates, related to high levels of HIV infection. National TB control programmes in areas of high HIV prevalence should no longer ignore treatment outcomes in patients with smear-negative PTB or EPTB.",
"title": "Treatment outcome of an unselected cohort of tuberculosis patients in relation to human immunodeficiency virus serostatus in Zomba Hospital, Malawi."
},
{
"docid": "6936141",
"text": "The HIV-1 protein Nef enhances viral pathogenicity and accelerates disease progression in vivo. Nef potentiates T cell activation by an unknown mechanism, probably by optimizing the intracellular environment for HIV replication. Using a new T cell reporter system, we have found that Nef more than doubles the number of cells expressing the transcription factors NF-kappaB and NFAT after TCR stimulation. This Nef-induced priming of TCR signaling pathways occurred independently of calcium signaling and involved a very proximal step before protein kinase C activation. Engagement of the TCR by MHC-bound Ag triggers the formation of the immunological synapse by recruiting detergent-resistant membrane microdomains, termed lipid rafts. Approximately 5-10% of the total cellular pool of Nef is localized within lipid rafts. Using confocal and real-time microscopy, we found that Nef in lipid rafts was recruited into the immunological synapse within minutes after Ab engagement of the TCR/CD3 and CD28 receptors. This recruitment was dependent on the N-terminal domain of Nef encompassing its myristoylation. Nef did not increase the number of cell surface lipid rafts or immunological synapses. Recently, studies have shown a specific interaction of Nef with an active subpopulation of p21-activated kinase-2 found only in the lipid rafts. Thus, the corecruitment of Nef and key cellular partners (e.g., activated p21-activated kinase-2) into the immunological synapse may underlie the increased frequency of cells expressing transcriptionally active forms of NF-kappaB and NFAT and the resultant changes in T cell activation.",
"title": "Nef is physically recruited into the immunological synapse and potentiates T cell activation early after TCR engagement."
},
{
"docid": "3662510",
"text": "OBJECTIVE To estimate the lost investment of domestically educated doctors migrating from sub-Saharan African countries to Australia, Canada, the United Kingdom, and the United States. DESIGN Human capital cost analysis using publicly accessible data. SETTINGS Sub-Saharan African countries. PARTICIPANTS Nine sub-Saharan African countries with an HIV prevalence of 5% or greater or with more than one million people with HIV/AIDS and with at least one medical school (Ethiopia, Kenya, Malawi, Nigeria, South Africa, Tanzania, Uganda, Zambia, and Zimbabwe), and data available on the number of doctors practising in destination countries. MAIN OUTCOME MEASURES The financial cost of educating a doctor (through primary, secondary, and medical school), assuming that migration occurred after graduation, using current country specific interest rates for savings converted to US dollars; cost according to the number of source country doctors currently working in the destination countries; and savings to destination countries of receiving trained doctors. RESULTS In the nine source countries the estimated government subsidised cost of a doctor's education ranged from $21,000 (£13,000; €15,000) in Uganda to $58,700 in South Africa. The overall estimated loss of returns from investment for all doctors currently working in the destination countries was $2.17bn (95% confidence interval 2.13bn to 2.21bn), with costs for each country ranging from $2.16m (1.55m to 2.78m) for Malawi to $1.41bn (1.38bn to 1.44bn) for South Africa. The ratio of the estimated compounded lost investment over gross domestic product showed that Zimbabwe and South Africa had the largest losses. The benefit to destination countries of recruiting trained doctors was largest for the United Kingdom ($2.7bn) and United States ($846m). CONCLUSIONS Among sub-Saharan African countries most affected by HIV/AIDS, lost investment from the emigration of doctors is considerable. Destination countries should consider investing in measurable training for source countries and strengthening of their health systems.",
"title": "The financial cost of doctors emigrating from sub-Saharan Africa: human capital analysis"
},
{
"docid": "8883846",
"text": "The Global HIV Vaccine Enterprise convened a two-day workshop in May of 2007 to discuss humoral immune responses to HIV and approaches to design vaccines that induce viral neutralizing and other potentially protective antibody responses. The goals of this workshop were to identify key scientific issues, gaps, and opportunities that have emerged since the Enterprise Strategic Plan was first published in 2005 [1], and to make recommendations that Enterprise stakeholders can use to plan new activities. Most effective viral vaccines work, at least in part, by generating antibodies that inactivate or neutralize the invading virus, and the existing data strongly suggest that an optimally effective HIV-1 vaccine should elicit potent antiviral neutralizing antibodies. However, unlike acute viral pathogens, HIV-1 chronically replicates in the host and evades the antibody response. This immune evasion, along with the large genetic variation among HIV-1 strains worldwide, has posed major obstacles to vaccine development. Current HIV vaccine candidates do not elicit neutralizing antibodies against most circulating virus strains, and thus the induction of a protective antibody response remains a major priority for HIV-1 vaccine development. For an antibody-based HIV-1 vaccine, progress in vaccine design is generally gauged by in vitro assays that measure the ability of vaccine-induced antibodies to neutralize a broad spectrum of viral isolates representing the major genetic subtypes (clades) of HIV-1 [2]. Although it is not known what magnitude and breadth of neutralization will predict protection in vaccine recipients, it is clear that current vaccine immunogens elicit antibodies that neutralize only a minority of circulating isolates. Thus, much progress needs to be made in this area. Also, though virus neutralization is considered a critical benchmark for a vaccine, this may not be the only benchmark for predicting success with antibody-based HIV-1 vaccine immunogens. The main targets for neutralizing antibodies to HIV-1 are the surface gp120 and trans-membrane gp41 envelope glycoproteins (Env) that mediate receptor and coreceptor binding and the subsequent membrane fusion events that allow the virus to gain entry into cells [3]. Antibodies neutralize the virus by binding these viral spikes and blocking virus entry into susceptible cells, such as CD4+ T cells [4,5]. In order to chronically replicate in the host, the virus exploits several mechanisms to shield itself against antibody recognition, including a dense outer coating of sugar molecules (N-linked glycans) and the strategic positioning of cysteine–cysteine loop structures on the gp120 molecule [6–8]. These shielding mechanisms, although highly effective, have vulnerabilities imposed by fitness constraints. Information on the precise location and molecular structure of these vulnerable regions could be valuable for the rational design of improved vaccine immunogens. Participants in the workshop identified four areas that, if given proper attention, could provide key information that would bring the field closer to an effective antibody-based HIV-1 vaccine: (1) structure-assisted immunogen design, (2) role of Fc receptors and complement, (3) assay standardization and validation, and (4) immunoregulation of B cell responses.",
"title": "Antibody-Based HIV-1 Vaccines: Recent Developments and Future Directions"
},
{
"docid": "13899137",
"text": "BACKGROUND Many mathematical models have investigated the impact of expanding access to antiretroviral therapy (ART) on new HIV infections. Comparing results and conclusions across models is challenging because models have addressed slightly different questions and have reported different outcome metrics. This study compares the predictions of several mathematical models simulating the same ART intervention programmes to determine the extent to which models agree about the epidemiological impact of expanded ART. METHODS AND FINDINGS Twelve independent mathematical models evaluated a set of standardised ART intervention scenarios in South Africa and reported a common set of outputs. Intervention scenarios systematically varied the CD4 count threshold for treatment eligibility, access to treatment, and programme retention. For a scenario in which 80% of HIV-infected individuals start treatment on average 1 y after their CD4 count drops below 350 cells/µl and 85% remain on treatment after 3 y, the models projected that HIV incidence would be 35% to 54% lower 8 y after the introduction of ART, compared to a counterfactual scenario in which there is no ART. More variation existed in the estimated long-term (38 y) reductions in incidence. The impact of optimistic interventions including immediate ART initiation varied widely across models, maintaining substantial uncertainty about the theoretical prospect for elimination of HIV from the population using ART alone over the next four decades. The number of person-years of ART per infection averted over 8 y ranged between 5.8 and 18.7. Considering the actual scale-up of ART in South Africa, seven models estimated that current HIV incidence is 17% to 32% lower than it would have been in the absence of ART. Differences between model assumptions about CD4 decline and HIV transmissibility over the course of infection explained only a modest amount of the variation in model results. CONCLUSIONS Mathematical models evaluating the impact of ART vary substantially in structure, complexity, and parameter choices, but all suggest that ART, at high levels of access and with high adherence, has the potential to substantially reduce new HIV infections. There was broad agreement regarding the short-term epidemiologic impact of ambitious treatment scale-up, but more variation in longer term projections and in the efficiency with which treatment can reduce new infections. Differences between model predictions could not be explained by differences in model structure or parameterization that were hypothesized to affect intervention impact.",
"title": "HIV Treatment as Prevention: Systematic Comparison of Mathematical Models of the Potential Impact of Antiretroviral Therapy on HIV Incidence in South Africa"
},
{
"docid": "1387104",
"text": "CONTEXT Venous thrombosis is a common complication in patients with cancer, leading to additional morbidity and compromising quality of life. OBJECTIVE To identify individuals with cancer with an increased thrombotic risk, evaluating different tumor sites, the presence of distant metastases, and carrier status of prothrombotic mutations. DESIGN, SETTING, AND PATIENTS A large population-based, case-control (Multiple Environmental and Genetic Assessment [MEGA] of risk factors for venous thrombosis) study of 3220 consecutive patients aged 18 to 70 years, with a first deep venous thrombosis of the leg or pulmonary embolism, between March 1, 1999, and May 31, 2002, at 6 anticoagulation clinics in the Netherlands, and separate 2131 control participants (partners of the patients) reported via a questionnaire on acquired risk factors for venous thrombosis. Three months after discontinuation of the anticoagulant therapy, all patients and controls were interviewed, a blood sample was taken, and DNA was isolated to ascertain the factor V Leiden and prothrombin 20210A mutations. MAIN OUTCOME MEASURE Risk of venous thrombosis. RESULTS The overall risk of venous thrombosis was increased 7-fold in patients with a malignancy (odds ratio [OR], 6.7; 95% confidence interval [CI], 5.2-8.6) vs persons without malignancy. Patients with hematological malignancies had the highest risk of venous thrombosis, adjusted for age and sex (adjusted OR, 28.0; 95% CI, 4.0-199.7), followed by lung cancer and gastrointestinal cancer. The risk of venous thrombosis was highest in the first few months after the diagnosis of malignancy (adjusted OR, 53.5; 95% CI, 8.6-334.3). Patients with cancer with distant metastases had a higher risk vs patients without distant metastases (adjusted OR, 19.8; 95% CI, 2.6-149.1). Carriers of the factor V Leiden mutation who also had cancer had a 12-fold increased risk vs individuals without cancer and factor V Leiden (adjusted OR, 12.1; 95% CI, 1.6-88.1). Similar results were indirectly calculated for the prothrombin 20210A mutation in patients with cancer. CONCLUSIONS Patients with cancer have a highly increased risk of venous thrombosis especially in the first few months after diagnosis and in the presence of distant metastases. Carriers of the factor V Leiden and prothrombin 20210A mutations appear to have an even higher risk.",
"title": "Malignancies, prothrombotic mutations, and the risk of venous thrombosis."
},
{
"docid": "14290854",
"text": "OBJECTIVE To describe variation in antibiotic prescribing for acute cough in contrasting European settings and the impact on recovery. DESIGN Cross sectional observational study with clinicians from 14 primary care research networks in 13 European countries who recorded symptoms on presentation and management. Patients followed up for 28 days with patient diaries. SETTING Primary care. PARTICIPANTS Adults with a new or worsening cough or clinical presentation suggestive of lower respiratory tract infection. MAIN OUTCOME MEASURES Prescribing of antibiotics by clinicians and total symptom severity scores over time. RESULTS 3402 patients were recruited (clinicians completed a case report form for 99% (3368) of participants and 80% (2714) returned a symptom diary). Mean symptom severity scores at presentation ranged from 19 (scale range 0 to 100) in networks based in Spain and Italy to 38 in the network based in Sweden. Antibiotic prescribing by networks ranged from 20% to nearly 90% (53% overall), with wide variation in classes of antibiotics prescribed. Amoxicillin was overall the most common antibiotic prescribed, but this ranged from 3% of antibiotics prescribed in the Norwegian network to 83% in the English network. While fluoroquinolones were not prescribed at all in three networks, they were prescribed for 18% in the Milan network. After adjustment for clinical presentation and demographics, considerable differences remained in antibiotic prescribing, ranging from Norway (odds ratio 0.18, 95% confidence interval 0.11 to 0.30) to Slovakia (11.2, 6.20 to 20.27) compared with the overall mean (proportion prescribed: 0.53). The rate of recovery was similar for patients who were and were not prescribed antibiotics (coefficient -0.01, P<0.01) once clinical presentation was taken into account. CONCLUSIONS Variation in clinical presentation does not explain the considerable variation in antibiotic prescribing for acute cough in Europe. Variation in antibiotic prescribing is not associated with clinically important differences in recovery. TRIAL REGISTRATION Clinicaltrials.gov NCT00353951.",
"title": "Variation in antibiotic prescribing and its impact on recovery in patients with acute cough in primary care: prospective study in 13 countries."
},
{
"docid": "14806256",
"text": "CONTEXT Use of antiretroviral drugs, including protease inhibitors, for treatment of human immunodeficiency virus (HIV) infection has been anecdotally associated with hepatotoxicity, particularly in persons coinfected with hepatitis C or B virus. OBJECTIVES To ascertain if incidence of severe hepatotoxicity during antiretroviral therapy is similar for all antiretroviral drug combinations, and to define the role of chronic viral hepatitis in its development. DESIGN Prospective cohort study. SETTING University-based urban HIV clinic. PATIENTS A total of 298 patients who were prescribed new antiretroviral therapies between January 1996 and January 1998, 211 (71%) of whom received protease inhibitors as part of combination therapy (median follow-up, 182 days) and 87 (29%) of whom received dual nucleoside analog regimens (median follow-up, 167 days). Chronic hepatitis C and B virus infection was present in 154 (52%) and 8 (2.7%) patients, respectively. MAIN OUTCOME MEASURE Severe hepatotoxicity, defined as a grade 3 or 4 change in levels of serum alanine aminotransferase and aspartate aminotransferase, evaluated before and during therapy. RESULTS Severe hepatotoxicity was observed in 31 (10.4%) of 298 patients (95% confidence interval [CI], 7.2%-14.4%). Ritonavir use was associated with a higher incidence of toxicity (30%; 95% CI, 17.9% -44.6%). However, no significant difference was detected in hepatotoxicity incidence in other treatment groups, ie, nucleoside analogs (5.7%; 95% CI, 1.2%-12.9%), nelfinavir (5.9%; 95% CI, 1.2%-16.2%), saquinavir (5.9%; 95% CI, 0.15%-28.7%), and indinavir(6.8%; 95% CI, 3.0%-13.1 %). Although chronicviral hepatitis was associated with an increased risk of severe hepatotoxicity among patients prescribed nonritonavir regimens (relative risk, 3.7; 95% CI, 1.0-11.8), most patients with chronic hepatitis C or B virus infection (88%) did not experience significant toxic effects. Rate of severe toxicity with use of any protease inhibitor in patients with hepatitis C infection was 12.2% (13/107; 95% CI, 6.6%-19.9%). In multivariate logistic regression, only ritonavir (adjusted odds ratio [AOR], 8.6; 95% CI, 3.0-24.6) and a CD4 cell count increase of more than 0.05 x 10(9)/L (AOR, 3.6; 95% CI, 1.0-12.9) were associated with severe hepatotoxicity. No irreversible outcomes were seen in patients with severe hepatotoxicity. CONCLUSIONS Our data indicate that use of ritonavir may increase risk of severe hepatotoxicity. Although hepatotoxicity may be more common in persons with chronic viral hepatitis, these data do not support withholding protease inhibitor therapy from persons coinfected with hepatitis B or C virus.",
"title": "Hepatotoxicity associated with antiretroviral therapy in adults infected with human immunodeficiency virus and the role of hepatitis C or B virus infection."
},
{
"docid": "23304931",
"text": "PURPOSE Diffuse large B-cell lymphoma (DLBCL) represents a clinically heterogeneous disease. Models based on immunohistochemistry predict clinical outcome. These include subdivision into germinal center (GC) versus non-GC subtypes; proliferation index (measured by expression of Ki-67), and expression of BCL-2, FOXP1, or B-lymphocyte-induced maturation protein (Blimp-1)/PRDM1. We sought to determine whether immunohistochemical analyses of biopsies from patients with DLBCL having HIV infection are similarly relevant for prognosis. PATIENTS AND METHODS We examined 81 DLBCLs from patients with AIDS in AMC010 (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP] v CHOP-rituximab) and AMC034 (etoposide, doxorubicin, vincristine, prednisone, and dose-adjusted cyclophosphamide plus rituximab concurrent v sequential) clinical trials and compared the immunophenotype with survival data, Epstein-Barr virus (EBV) positivity, and CD4 counts. RESULTS The GC and non-GC subtypes of DLBCL did not differ significantly with respect to overall survival or CD4 count at cancer presentation. EBV could be found in both subtypes of DLBCL, although less frequently in the GC subtype, and did not affect survival. Expression of FOXP1, Blimp-1/PRDM1, or BCL-2 was not correlated with the outcome in patients with AIDS-related DLBCL. CONCLUSION These data indicate that with current treatment strategies for lymphoma and control of HIV infection, commonly used immunohistochemical markers may not be clinically relevant in HIV-infected patients with DLBCL. The only predictive immunohistochemical marker was found to be Ki-67, where a higher proliferation index was associated with better survival, suggesting a better response to therapy in patients whose tumors had higher proliferation rates.",
"title": "Immunophenotypic analysis of AIDS-related diffuse large B-cell lymphoma and clinical implications in patients from AIDS malignancies consortium clinical trials 010 and 034"
},
{
"docid": "21323758",
"text": "Tafamidis is a transthyretin (TTR) stabilizer able to prevent TTR tetramer dissociation. There have been a few encouraging studies on Tafamidis efficacy in early-onset inherited transthyretin amyloidosis (ATTR) due to Val30Met mutation. However, less is known about its efficacy in later disease stages and in non-Val30Met mutations. We performed a multi-center observational study on symptomatic ATTR patients prescribed to receive Tafamidis. We followed up patients according to a standardized protocol including general medical, cardiological and neurological assessments at baseline and every 6 months up to 3 years. Sixty-one (42 males) patients were recruited. Only 28 % of enrolled subjects had the common Val30Met mutation, mean age of onset was remarkably late (59 years) and 18 % was in advanced disease stage at study entry. Tafamidis proved safe and well-tolerated. One-third of patients did not show significant progression along 36 months, independently from mutation type and disease stage. Neurological function worsened particularly in the first 6 months but progression slowed significantly thereafter. Autonomic function remained stable in 33 %, worsened in 56 % and improved in 10 %. Fifteen percent of patients showed cardiac disease progression and 30 % new onset of cardiomyopathy. Overall, Tafamidis was not able to prevent functional progression of the disease in 23 (43 %) subjects, including 16 patients who worsened in their walking ability and 12 patients who reached a higher NYHA score during the follow-up period. A higher mBMI at baseline was associated with better preservation of neurological function. In conclusion, neuropathy and cardiomyopathy progressed in a significant proportion of patients despite treatment. However, worsening of neurological function slowed after the first 6 months and also subjects with more advanced neuropathy, as well as patients with non-Val30Met mutation, benefited from treatment. Body weight preservation is an important favorable prognostic factor.",
"title": "Monitoring effectiveness and safety of Tafamidis in transthyretin amyloidosis in Italy: a longitudinal multicenter study in a non-endemic area"
},
{
"docid": "356218",
"text": "BACKGROUND Pregnant women with mild preexisting renal disease have relatively few complications of pregnancy, but the risks of maternal and obstetrical complications in women with moderate or severe renal insufficiency remain uncertain. METHODS We determined the frequency and types of maternal and obstetrical complications and the outcomes of pregnancy in 67 women with primary renal disease (82 pregnancies). All the women had initial serum creatinine concentrations of at least 1.4 mg per deciliter (124 mumol per liter) and gestations that continued beyond the first trimester. RESULTS The mean (+/- SD) serum creatinine concentration increased from 1.9 +/- 0.8 mg per deciliter (168 +/- 71 mumol per liter) in early pregnancy to 2.5 +/- 1.3 mg per deciliter (221 +/- 115 mumol per liter) in the third trimester. The frequency of hypertension rose from 28 percent at base line to 48 percent in the third trimester, and that of high-grade proteinuria (urinary protein excretion, > 3000 mg per liter) from 23 percent to 41 percent. For the 70 pregnancies (57 women) for which data were available during pregnancy and immediately post partum, pregnancy-related loss of maternal renal function occurred in 43 percent. Eight of these pregnancies (10 percent of the total) were associated with rapid acceleration of maternal renal insufficiency. Obstetrical complications included a high rate of preterm delivery (59 percent) and growth retardation (37 percent). The infant survival rate was 93 percent. CONCLUSIONS Among pregnant women with moderate or severe renal insufficiency, the rates of complications due to worsening renal function, hypertension, and obstetrical complications are increased, but fetal survival is high.",
"title": "Outcome of pregnancy in women with moderate or severe renal insufficiency."
},
{
"docid": "31363207",
"text": "BACKGROUND Patients with human immunodeficiency virus (HIV) infection and tuberculosis have an increased risk of death, treatment failure, and relapse. METHODS A systematic review and meta-analysis of randomized, controlled trials and cohort studies was conducted to evaluate the impact of duration and dosing schedule of rifamycin and use of antiretroviral therapy in the treatment of active tuberculosis in HIV-positive patients. In included studies, the initial tuberculosis diagnosis, failure, and/or relapse were microbiologically confirmed, and patients received standardized rifampin- or rifabutin-containing regimens. Pooled cumulative incidence of treatment failure, death during treatment, and relapse were calculated using random-effects models. Multivariable meta-regression was performed using negative binomial regression. RESULTS After screening 5158 citations, 6 randomized trials and 21 cohort studies were included. Relapse was more common with regimens using 2 months rifamycin (adjusted risk ratio, 3.6; 95% confidence interval, 1.1-11.7) than with regimens using rifamycin for at least 8 months. Compared with daily therapy in the initial phase (n=3352 patients from 35 study arms), thrice-weekly therapy (n=211 patients from 5 study arms) was associated with higher rates of failure (adjusted risk ratio, 4.0; 95% confidence interval, 1.5-10.4) and relapse [adjusted risk ratio, 4.8; 95% confidence interval, 1.8-12.8). There were trends toward higher relapse rates if rifamycins were used for only 6 months, compared with > or =8 months, or if antiretroviral therapy was not used. CONCLUSIONS This review raises serious concerns regarding current recommendations for treatment of HIV-tuberculosis coinfection. The data suggest that at least 8 months duration of rifamycin therapy, initial daily dosing, and concurrent antiretroviral therapy might be associated with better outcomes, but adequately powered randomized trials are urgently needed to confirm this.",
"title": "Treatment of active tuberculosis in HIV-coinfected patients: a systematic review and meta-analysis."
},
{
"docid": "21274496",
"text": "Simian immunodeficiency virus (SIV) naturally infects non-human primates in Africa. To date, 40 SIVs have been described both in natural hosts and in heterologous species. These viruses are highly diverse and the majority cluster in 6 relatively equidistant phylogenetic lineages. At least 8 SIVs are currently considered as recombinant viruses, based on different clustering patterns in different genomic regions. Only three types of genomes are known, based on the number of accessory genes: vpr-containing genomes, vpr-vpx containing genomes and vpr-vpu-containing genomes. vpx resulted by a duplication of the vpr gene following non-homologous recombination and is characteristic of SIVs infecting the Papionini tribe of monkeys and HIV-2 in humans. vpu is characteristic of SIVcpz and HIV-1 and may have originated from a recombination involving SIVs from cercopitecini monkeys. SIV seems to be non-pathogenic in the vast majority of natural hosts in spite of a high levels of viral replication. This is probably a consequence of virus-host adaptation, in which the incubation period of the disease generally exceeds the life span of the African primate host. SIVs also have a high propensity for cross-species transmission. In the new host, the outcome may vary from inapparent infection to highly pathogenic, the former being reported for African monkeys, whereas the latter being observed in macaques and humans. The high diversity of SIVs was generated by a high mutation rate due to a low fidelity of the reverse-transcriptase and active viral and host cell turnover, host-dependent evolution and recombination. Cross-species transmission is not rare, however preferential host switching may drive the majority of cross-species transmissions. Numerous SIVs tested so far are able to grow in vitro on human PBMC, therefore it has been postulated that SIV represents a threat for infection of humans in Central Africa and that AIDS is a zoonosis. However, although the simian origin of the two HIV types is broadly acknowledged, there are no data that AIDS is acquired like a zoonosis. SIV may undergo adaptation in the new human host in order to emerge in the general population. The study of SIV in their natural hosts should provide important clues to the real threat to human populations and also elucidate the mechanisms associated with a long-term persistent viral infection without clinical consequences for the host.",
"title": "The history of SIVS and AIDS: epidemiology, phylogeny and biology of isolates from naturally SIV infected non-human primates (NHP) in Africa."
},
{
"docid": "23377475",
"text": "The previous conventional wisdom that survivors of acute kidney injury (AKI) tend to do well and fully recover renal function appears to be flawed. AKI can cause end-stage renal disease (ESRD) directly, and increase the risk of developing incident chronic kidney disease (CKD) and worsening of underlying CKD. In addition, severity, duration, and frequency of AKI appear to be important predictors of poor patient outcomes. CKD is an important risk factor for the development and ascertainment of AKI. Experimental data support the clinical observations and the bidirectional nature of the relationships between AKI and CKD. Reductions in renal mass and nephron number, vascular insufficiency, cell cycle disruption, and maladaptive repair mechanisms appear to be important modulators of progression in patients with and without coexistent CKD. Distinction between AKI and CKD may be artificial. Consideration should be given to the integrated clinical syndrome of diminished GFR, with acute and chronic stages, where spectrum of disease state and outcome is determined by host factors, including the balance of adaptive and maladaptive repair mechanisms over time. Physicians must provide long-term follow-up to patients with first episodes of AKI, even if they presented with normal renal function.",
"title": "Acute kidney injury and chronic kidney disease: an integrated clinical syndrome."
},
{
"docid": "27466734",
"text": "Objectives To develop and validate updated QRISK3 prediction algorithms to estimate the 10 year risk of cardiovascular disease in women and men accounting for potential new risk factors. Design Prospective open cohort study. Setting General practices in England providing data for the QResearch database. Participants 1309 QResearch general practices in England: 981 practices were used to develop the scores and a separate set of 328 practices were used to validate the scores. 7.89 million patients aged 25-84 years were in the derivation cohort and 2.67 million patients in the validation cohort. Patients were free of cardiovascular disease and not prescribed statins at baseline. Methods Cox proportional hazards models in the derivation cohort to derive separate risk equations in men and women for evaluation at 10 years. Risk factors considered included those already in QRISK2 (age, ethnicity, deprivation, systolic blood pressure, body mass index, total cholesterol: high density lipoprotein cholesterol ratio, smoking, family history of coronary heart disease in a first degree relative aged less than 60 years, type 1 diabetes, type 2 diabetes, treated hypertension, rheumatoid arthritis, atrial fibrillation, chronic kidney disease (stage 4 or 5)) and new risk factors (chronic kidney disease (stage 3, 4, or 5), a measure of systolic blood pressure variability (standard deviation of repeated measures), migraine, corticosteroids, systemic lupus erythematosus (SLE), atypical antipsychotics, severe mental illness, and HIV/AIDs). We also considered erectile dysfunction diagnosis or treatment in men. Measures of calibration and discrimination were determined in the validation cohort for men and women separately and for individual subgroups by age group, ethnicity, and baseline disease status. Main outcome measures Incident cardiovascular disease recorded on any of the following three linked data sources: general practice, mortality, or hospital admission records. Results 363 565 incident cases of cardiovascular disease were identified in the derivation cohort during follow-up arising from 50.8 million person years of observation. All new risk factors considered met the model inclusion criteria except for HIV/AIDS, which was not statistically significant. The models had good calibration and high levels of explained variation and discrimination. In women, the algorithm explained 59.6% of the variation in time to diagnosis of cardiovascular disease (R2, with higher values indicating more variation), and the D statistic was 2.48 and Harrell's C statistic was 0.88 (both measures of discrimination, with higher values indicating better discrimination). The corresponding values for men were 54.8%, 2.26, and 0.86. Overall performance of the updated QRISK3 algorithms was similar to the QRISK2 algorithms. Conclusion Updated QRISK3 risk prediction models were developed and validated. The inclusion of additional clinical variables in QRISK3 (chronic kidney disease, a measure of systolic blood pressure variability (standard deviation of repeated measures), migraine, corticosteroids, SLE, atypical antipsychotics, severe mental illness, and erectile dysfunction) can help enable doctors to identify those at most risk of heart disease and stroke.",
"title": "Development and validation of QRISK3 risk prediction algorithms to estimate future risk of cardiovascular disease: prospective cohort study"
},
{
"docid": "2638387",
"text": "High mutation frequency during reverse transcription has a principal role in the genetic variation of primate lentiviral populations. It is the main driving force for the generation of drug resistance and the escape from immune surveillance. G to A hypermutation is one of the characteristics of primate lentiviruses, as well as other retroviruses, during replication in vivo and in cell culture. The molecular mechanisms of this process, however, remain to be clarified. Here, we demonstrate that CEM15 (also known as apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3G; APOBEC3G), an endogenous inhibitor of human immunodeficiency virus type 1 (HIV-1) replication, is a cytidine deaminase and is able to induce G to A hypermutation in newly synthesized viral DNA. This effect can be counteracted by the HIV-1 virion infectivity factor (Vif). It seems that this viral DNA mutator is a viral defence mechanism in host cells that may induce either lethal hypermutation or instability of the incoming nascent viral reverse transcripts, which could account for the Vif-defective phenotype. Importantly, the accumulation of CEM15-mediated non-lethal hypermutation in the replicating viral genome could potently contribute to the genetic variation of primate lentiviral populations.",
"title": "The cytidine deaminase CEM15 induces hypermutation in newly synthesized HIV-1 DNA"
},
{
"docid": "25816994",
"text": "BACKGROUND Angiotensin receptor blockers (ARB) and angiotensin converting enzyme (ACE) inhibitors are known to reduce proteinuria. Their combination might be more effective than either treatment alone, but long-term data for comparative changes in renal function are not available. We investigated the renal effects of ramipril (an ACE inhibitor), telmisartan (an ARB), and their combination in patients aged 55 years or older with established atherosclerotic vascular disease or with diabetes with end-organ damage. METHODS The trial ran from 2001 to 2007. After a 3-week run-in period, 25 620 participants were randomly assigned to ramipril 10 mg a day (n=8576), telmisartan 80 mg a day (n=8542), or to a combination of both drugs (n=8502; median follow-up was 56 months), and renal function and proteinuria were measured. The primary renal outcome was a composite of dialysis, doubling of serum creatinine, and death. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00153101. FINDINGS 784 patients permanently discontinued randomised therapy during the trial because of hypotensive symptoms (406 on combination therapy, 149 on ramipril, and 229 on telmisartan). The number of events for the composite primary outcome was similar for telmisartan (n=1147 [13.4%]) and ramipril (1150 [13.5%]; hazard ratio [HR] 1.00, 95% CI 0.92-1.09), but was increased with combination therapy (1233 [14.5%]; HR 1.09, 1.01-1.18, p=0.037). The secondary renal outcome, dialysis or doubling of serum creatinine, was similar with telmisartan (189 [2.21%]) and ramipril (174 [2.03%]; HR 1.09, 0.89-1.34) and more frequent with combination therapy (212 [2.49%]: HR 1.24, 1.01-1.51, p=0.038). Estimated glomerular filtration rate (eGFR) declined least with ramipril compared with telmisartan (-2.82 [SD 17.2] mL/min/1.73 m(2)vs -4.12 [17.4], p<0.0001) or combination therapy (-6.11 [17.9], p<0.0001). The increase in urinary albumin excretion was less with telmisartan (p=0.004) or with combination therapy (p=0.001) than with ramipril. INTERPRETATION In people at high vascular risk, telmisartan's effects on major renal outcomes are similar to ramipril. Although combination therapy reduces proteinuria to a greater extent than monotherapy, overall it worsens major renal outcomes.",
"title": "Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial."
},
{
"docid": "45461275",
"text": "BACKGROUND PEPFAR, national governments, and other stakeholders are investing unprecedented resources to provide HIV treatment in developing countries. This study reports empirical data on costs and cost trends in a large sample of HIV treatment sites. DESIGN In 2006-2007, we conducted cost analyses at 43 PEPFAR-supported outpatient clinics providing free comprehensive HIV treatment in Botswana, Ethiopia, Nigeria, Uganda, and Vietnam. METHODS We collected data on HIV treatment costs over consecutive 6-month periods starting from scale-up of dedicated HIV treatment services at each site. The study included all patients receiving HIV treatment and care at study sites [62,512 antiretroviral therapy (ART) and 44,394 pre-ART patients]. Outcomes were costs per patient and total program costs, subdivided by major cost categories. RESULTS Median annual economic costs were US$ 202 (2009 USD) for pre-ART patients and US$ 880 for ART patients. Excluding antiretrovirals, per patient ART costs were US$ 298. Care for newly initiated ART patients cost 15-20% more than for established patients. Per patient costs dropped rapidly as sites matured, with per patient ART costs dropping 46.8% between first and second 6-month periods after the beginning of scale-up, and an additional 29.5% the following year. PEPFAR provided 79.4% of funding for service delivery, and national governments provided 15.2%. CONCLUSION Treatment costs vary widely between sites, and high early costs drop rapidly as sites mature. Treatment costs vary between countries and respond to changes in antiretroviral regimen costs and the package of services. Whereas cost reductions may allow near-term program growth, programs need to weigh the trade-off between improving services for current patients and expanding coverage to new patients.",
"title": "The cost of providing comprehensive HIV treatment in PEPFAR-supported programs."
},
{
"docid": "341324",
"text": "BACKGROUND Under the Revised National Tuberculosis Control Programme of India, patients with new smear-positive pulmonary tuberculosis are treated with a thrice-weekly regimen of antitubercular drugs (2H(3)R(3)Z(3)E(3)/4H(3)R(3) [H isoniazid, R rifampicin, Z pyrazinamide and E ethambutol]) for 6 months. We conducted a retrospective analysis of the efficacy andtolerability of this regimen under clinical trial conditions in HIV-negative patients with newly diagnosed smear-positive pulmonary tuberculosis. METHODS We retrospectively analysed the data on patients assigned to the control regimen (2H (3)R(3)Z(3)E(3)/4H(3)R(3)) in two clinical trials during 2001-06 at the National Institute for Research in Tuberculosis, Chennai, India. RESULTS Of the 268 patients treated with this regimen, data for efficacy analysis were available for 249. At the end of treatment, of 249 patients, 238 (96%) had a favourable status. Treatment failure occurred in the remaining 11: 7 in whom the organisms were initially drug-susceptible and 4 with initial drug resistance. Of the 238 patients who had a favourable status at the end of treatment, 14 (6%) had recurrence of tuberculosis during the following 24 months. In the intention-to-treat analysis, 245 (94%) of 262 patients had a favourable status at the end of treatment. Of the 28 patients with initial drug resistance, 24 (86%) had a favourable outcome. Only 4 of these 24 patients were found to have recurrence of tuberculosis in 2 years of follow-up. Among the 221 patients initially infected with drug-susceptible organisms, drug resistance did not develop in any of the 7 patients in whom the treatment failed or the 10 who had recurrence of tuberculosis. Further, 5 of the 7 patients in whom the treatment failed continued to excrete drug-susceptible bacilli at 6 months. Adverse drug reactions were observed in 38 (14%) of the 262 patients. Only 3 (1.1%) needed a modification in the treatment. CONCLUSION This thrice-weekly 6-month regimen of antitubercular drugs, when administered under full supervision, is associated with a high rate of favourable treatment outcomes in HIV-negative patients with newly diagnosed sputum smearpositive pulmonary tuberculosis. There are few adverse drug reactions in these patients.",
"title": "Efficacy of the 6-month thrice-weekly regimen in the treatment of new sputum smear-positive pulmonary tuberculosis under clinical trial conditions."
},
{
"docid": "14319754",
"text": "BACKGROUND Highly active antiretroviral therapy (HAART) is being scaled up in developing countries. We compared baseline characteristics and outcomes during the first year of HAART between HIV-1-infected patients in low-income and high-income settings. METHODS 18 HAART programmes in Africa, Asia, and South America (low-income settings) and 12 HIV cohort studies from Europe and North America (high-income settings) provided data for 4810 and 22,217, respectively, treatment-naïve adult patients starting HAART. All patients from high-income settings and 2725 (57%) patients from low-income settings were actively followed-up and included in survival analyses. FINDINGS Compared with high-income countries, patients starting HAART in low-income settings had lower CD4 cell counts (median 108 cells per muL vs 234 cells per muL), were more likely to be female (51%vs 25%), and more likely to start treatment with a non-nucleoside reverse transcriptase inhibitor (NNRTI) (70%vs 23%). At 6 months, the median number of CD4 cells gained (106 cells per muL vs 103 cells per muL) and the percentage of patients reaching HIV-1 RNA levels lower than 500 copies/mL (76%vs 77%) were similar. Mortality was higher in low-income settings (124 deaths during 2236 person-years of follow-up) than in high-income settings (414 deaths during 20,532 person-years). The adjusted hazard ratio (HR) of mortality comparing low-income with high-income settings fell from 4.3 (95% CI 1.6-11.8) during the first month to 1.5 (0.7-3.0) during months 7-12. The provision of treatment free of charge in low-income settings was associated with lower mortality (adjusted HR 0.23; 95% CI 0.08-0.61). INTERPRETATION Patients starting HAART in resource-poor settings have increased mortality rates in the first months on therapy, compared with those in developed countries. Timely diagnosis and assessment of treatment eligibility, coupled with free provision of HAART, might reduce this excess mortality.",
"title": "The Antiretroviral Therapy in Lower Income Countries (ART-LINC) Collaboration and ART Cohort Collaboration (ART-CC) groups Summary"
}
] |
5958
|
What to do with $50,000?
|
[
{
"docid": "345052",
"text": "Considered a down payment on a house? Some illiquid assets? Otherwise you are doing 'responsible' get rich slow (read: get rich old) type things. And this question only invites opinion based answer. You tried futures and don't want to take that kind of risk again with your $50,000, so thats that",
"title": ""
},
{
"docid": "315930",
"text": "Here is some good advice, read your UCO prospectus. It seems to hold 20% of it's value ($600MM out of $3B) via 13800 of the Apr 21st 2015 contracts. (expiring in 30 days) Those will be rolled very quickly into the May contracts at a significant loss of NAV. (based on current oil futures chains) Meaning if crude oil stays exactly the same price, you'd still lose 1% (5% spread loss * .20% the percentage of NAV based off futures contracts) on the roll each month. Their other $2.4Billion is held in swaptions or cash, unsure how to rate that exposure. All I know is those 13,800 contracts are in contango danger during roll week for the next few months (IMO). I wonder if there is a website that tracks inflows and outflows to see if they match up with before and after the roll periods. http://www.proshares.com/funds/uco_daily_holdings.html How Oil ETFs Work Many oil ETFs invest in oil futures contracts. An oil futures contract is a commitment to buy a given amount of crude oil at a given price on a particular date in the future. Since the purpose of oil ETFs is only to serve as an investment vehicle to track the price of oil, the creators of the fund have no interest in stockpiling actual oil. Therefore, oil ETFs such as USO periodically “roll over” their futures contracts by selling the contracts that are approaching expiration and buying contracts that expire farther into the future. The Contango Problem While this process of continually rolling over futures contracts may seem like a great way to track the price of crude oil, there’s a practical problem with the method: contango. The rollover method would work perfectly if oil funds could sell their expiring contracts for the exact same price that they pay for the futures contracts they buy each month. However, in reality, it’s often true that oil futures contracts get more expensive the farther their expiration date is in the future. That means that every time the oil ETFs roll over their contracts, they lose the difference in value between the contracts they sell and the contracts they buy. That’s why funds like USO, which invests only in WTI light, sweet crude oil futures contracts, don’t directly track the performance of the WTI crude oil spot price. http://www.etftrends.com/2015/01/positioning-for-an-oil-etf-rebound-watch-for-contango/ Due to these reasons, I'd deem UCO for swing trading, not for 'investing' (buy-and-hold). Maybe later I'll remember why one shouldn't buy and hold leveraged vehicles (leverage slippage/decay). Do you have an exit price in mind ? or are you buy and hold ?",
"title": ""
},
{
"docid": "246114",
"text": "Before anything else, pay down any debt at higher interest rates. Best guaranteed return on investment you can get. What do you plan to use the money for, when, with how much advance planning? How risk-tolerant are you, and how patient are you ? Would you see a dip in an asset's value as lost money or a buying opportunity? A good financial advisor -- and I mean one who is ONLY an advisor and not trying to sell you anything but their services -- can take answers of that sort and recommend a mix of investment types that will suit your needs. Knowing that balance, you can the pick specific investments to suit. (I remain a fan of low-fee index funds as a painless way to get good diversification, with some small percentage for more active trading if you really want to invest the effort and are convinced you can beat the odds.) Other answers here on the personal finance discussion go into this in detail, so I don't think it's worth repeating here unless there's something really unusual about your situation.",
"title": ""
}
] |
[
{
"docid": "24306",
"text": "Although I posted this question more than a year ago, I subsequently read information which may be of use as an answer, specifically regarding Pritchard Stockbrokers in the UK several years ago, in which the FSCS stepped in to compensate investors, as detailed in the following: http://www.fscs.org.uk/what-we-cover/questions-and-answers/qas-about-pritchard-stock-6n940n01k/ http://www.ft.com/cms/s/0/89957c56-21e4-11e3-9b55-00144feab7de.html#axzz3crZYbGZ9 For reference, in case the links above are at some point in future taken offline, the FSCS FAQ states: Q: I had “deposited” money with Pritchard so can I expect £85,000 compensation from FSCS? A: No. Pritchard was not a deposit-taker so the money held does not qualify under regulatory rules as a deposit. The money will be treated as an investment, which carries maximum FSCS compensation of £50,000 per person. FSCS has no discretion to pay any more. Q: What happens if my losses are over the FSCS maximum of £50,000 and I accept the FSCS’s compensation? A: If you choose to accept compensation from FSCS, you will be required to assign (or legally transfer) to FSCS all of your rights to claim in the Administration. FSCS will then claim in the Administration standing “in your shoes” and will claim for the whole of your loss, even if it was over £50,000. When FSCS receives the dividends in your place it will then pay to you any amounts recovered to ensure that you do not suffer a disadvantage for having accepted FSCS compensation first. Example 1: Loss = £80,000 FSCS compensation = £50,000 Dividend of 50p/£ received by FSCS = £40,000 FSCS pays £30,000 to claimant so he is fully compensated (total £80,000), and retains £10,000 recovery for itself Example 2: Loss = £100,000 FSCS compensation = £50,000 Dividend of 50p/£ received by FSCS = £50,000 FSCS pays £50,000 to claimant so he is fully compensated (total £100,000), and retains nothing for itself FSCS does not have to have make a full recovery of its £50,000 before it starts paying its dividend recovery on to claimants. Claimants are not compelled to claim from FSCS, or to accept the FSCS offer of compensation. If a person does not want to transfer his legal rights to claim in the Administration to FSCS in return for accepting the payment of compensation, then s/he can decline our compensation and continue his claim in the Administration. After s/he has received the dividend(s), s/he can then return to FSCS to claim for any remaining shortfall. Therefore, the answer provided by @DumbCoder was correct, but in circumstances where fraudulent activity would mean otherwise, the FSCS was willing to intervene on the behalf of investors.",
"title": ""
},
{
"docid": "489278",
"text": "The deposit insurance isn't provided by the bank; it's provided by the Singapore Deposit Insurance Corporation (SDIC). In the event that the bank fails or is declared insolvent, the SDIC will pay deposit holders their total balance in all accounts with that bank, up to S$50,000. If you hold S$60,000 in all of your insured accounts, you'll only receive S$50,000 if the bank fails. The SDIC provides an example page with sample calculations, and this is exactly what they show. If you deposit an amount greater than $S50,000, it's only insured up to S$50,000. So does it mean one should open multiple accounts under different banks to spread the money around and maintain only S$50,000 in one deposit account? This is one option. The calculations page I linked to above gives this reminder: Deposits are not insured separately in each branch office of a DI Scheme member i.e. all your eligible accounts maintained with different branches of a DI Scheme member are aggregated and insured up to S$50,000. This seems like common sense, but it's important to remember that if you open an account with two branch offices of Bank A, your deposits are aggregated and insured up to S$50,000. The SDIC insurance is per institution (called a Deposit Insurance Member), not per branch. If you hold S$45,000 in each branch office, for a total of S$90,000, you're still only insured up to S$50,000 for that bank. If you want to spread out your accounts between multiple banks, make sure they're different banks, not just different branches. Another option, if it applies to you, is to open a joint account with your spouse. In the FAQ page, the SDIC gives this example under point 14: if you and your husband have a joint account with S$70,000, and you have a separate account of S$20,000, your total deposits of S$55,000 will be covered to the maximum of S$50,000. The deposit of $S70,000 is split evenly between the spouses, so in the eyes of the SDIC, each are holding S$35,000. Then, the husband's additional S$20,000 is added to S$35,000 for a total of S$50,000. This is then insured up to S$50,000 as usual. I'm sure there are other options specific to Singapore that I'm not aware of; if you're well above the limit, i.e. holding millions of dollars, I'm sure a professional accountant in Singapore could guide you further.",
"title": ""
},
{
"docid": "571711",
"text": "I'm not an expert, but here's my $0.02. Deductions for business expenses are subject to the 2% rule. In other words, you can only deduct that which exceeds 2% of your AGI (Adjusted Gross Income). For example, say you have an AGI of $50,000, and you buy a laptop that costs $800. You won't get a write-off from that, because 2% of $50,000 is $1,000, and you can only deduct business-related expenses in excess of that $1,000. If you have an AGI of $50,000 and buy a $2,000 laptop, you can deduct a maximum of $1,000 ($2,000 minus 2% of $50,000 is $2,000 - $1,000 = $1,000). Additionally, you can write off the laptop only to the extent that you use it for business. So in other words, if you have an AGI of $50,000 and buy that $2,000 laptop, but only use it 50% for business, you can only write off $500. Theoretically, they can ask for verification of the business use of your laptop. A log or a diary would be what I would provide, but I'm not an IRS agent.",
"title": ""
},
{
"docid": "174033",
"text": "If I donate $10,000 to charity then I can deduct that $10,000 from my income and not pay income taxes on it. So if I make $50,000 a year then I will only pay income taxes on $40,000 instead of $50,000 since I donated $10,000 to charity. This is what is meant when charity contributions are said to be tax deductible. Don't feel like you have to donate to charity. You owe no one anything. You do more for others by working (assuming you work in the private sector). If you know of someone personally that is in need of aid then you could give them some help directly. I find this more effective then blindly dumping money in a bureaucratic, inefficient charity. I also find there are very few people in need of charity. Personally, I think charity donations are a way for people to feel good about themselves. They rarely care if their donations are effective.",
"title": ""
},
{
"docid": "226053",
"text": "Basically the first thing you should do before you invest your money is to learn about investing and learn about what you want to invest in. Another thing to think about is that usually low risk can also mean low returns. As you are quite young and have some savings put aside you should generally aim for higher risk higher return investments and then when you start to reach retirement age aim for less risky lower return investments. In saying that, just because an investment is considered high risk does not mean you have to be exposed to the full risk of that investment. You do this by managing your risk to an acceptable level which will allow you to sleep at night. To do this you need to learn about what you are investing in. As an example about managing your risk in an investment, say you want to invest $50,000 in shares. If you put the full $50,000 into one share and that share price drops dramatically you will lose a large portion of your money straight away. If instead you spent a maximum of $10,000 on 5 different shares, even if one of them falls dramatically, you still have another 4 which may be doing a lot better thus minimising your losses. To take it one step further you might say if anyone of the shares you bought falls by 20% then you will sell those shares and limit your losses to $2000 per share. If the worst case scenario occurred and all 5 of your shares fell during a stock market crash you would limit your total losses to $10,000 instead of $50,000. Most successful investors put just as much if not more emphasis on managing the risk on their investments and limiting their losses as they do in selecting the investments. As I am not in the US, I cannot really comment whether it is the right time to buy property over there, especially as the market conditions would be different in different states and in different areas of each state. However, a good indication of when to buy properties is when prices have dropped and are starting to stabilise. As you are renting at the moment one option you might want to look at is buying a place to live in so you don't need to rent any more. You can compare your current rent payment with the mortgage payment if you were to buy a house to live in. If your mortgage payments are lower than your rent payments then this could be a good option. But whatever you do make sure you learn about it first. Make sure you spend the time looking at for sale properties for a few months in the area you want to buy before you do buy. This will give you an indication of how much properties in that area are really worth and if prices are stable, still falling or starting to go up. Good luck, and remember, research, research and more research. Even if you are to take someone elses advice and recommendations, you should learn enough yourself to be able to tell if their advice and recommendations make sense and are right for your current situation.",
"title": ""
},
{
"docid": "387030",
"text": "While the other answers are good, I wanted to expand a little on why I feel a ROTH is a bad way to go unless you are young. First, let's pretend you have a 25% tax rate. And your investments will go up 5% per year for 10 years. You contribute 6% of income for one year. You can do a traditional or a roth 401k/IRA. Here's the math: Traditional: 6% of income invested. Grows at 5% for 10 years. Taxed at 25% on withdrawl. = (Income * 6%) * (1.05 ^ 10) * (100% - 25%) = (Income * 6%) * 1.63 * .75 = 7.33% of your original income - but this is after taxes ROTH: Taxes taken out of income. Then 6% of that goes into the fund(s). Still grows at 5% for 10 years. Not taxed at withdrawl. = (Income * (100% - 25%) * 6%) * (1.05 ^ 10) = (Income * 75% * 6%) * 1.63 = 7.33% of your original income - again this is after taxes. Look familiar? They are the same. It's the simple transitive property of mathematics. So why do a traditional vs. a ROTH? The reason is that your tax bracket changes. This changes because your income changes. Say when you retire you plan to have your home or vehicle paid for. You expect to be able to live on $50,000 per year. This means when you make MORE than $50,000 you should do a traditional plan and when you make less than this you should do a ROTH plan. Example: You make $100,000 and your upper bracket is now 30%. You save 30% by doing a traditional and then pay back 10, 20, and 30% as you withdraw a salary of $50,000. Traditional = better. Example: You make $30,000 annually. Your upper bracket is 20%. You pay 20% on a roth. Then you withdraw funds to get to $50,000 anually and never pay the higher bracket. Roth = better. ROTH advocates typically bring up tax rates. Of course they will go up they insist. So you always should do a ROTH. Not so fast. Taxes have gone down in recent years (No one please start a political debate with me. Some went up, some went down, but overall, federal income rates dropped). Even if taxes rose 5%, a traditional will still be better than a ROTH in many cases.",
"title": ""
},
{
"docid": "315508",
"text": "WhyHellYeah, What do you do for a living? I am an accountant in the energy industry. I will never be a union member and at $50,000 a year I already make more money than 75% of people and 50% of all households in the USA... I am in the position where Unions are a threat to my lifestyle and income... But I do know that collective bargaining is the only thing that prevents capitol from exploiting labor. I'm really curious why you feel differently? >but EEOC is expanding Whats wrong with an agency that is tasked to enforce laws against workplace discrimination expanding? Do you think that workplaces should discriminate against employees?",
"title": ""
},
{
"docid": "325064",
"text": "It depends entirely on what you're improving and what you're spending. Taking the kitchen for example, if you're replacing a tired 1960's kitchen with cheap but functional IKEA units and appliances, and you're doing as much of the work as possible yourself, you will definitely see a good return. However if you're spending $50,000 on a Poggenpohl kitchen to be fitted by professionals your ROI is going to be your enjoyment of the kitchen over the years and not financial.",
"title": ""
},
{
"docid": "144033",
"text": "The Creation/Redemption mechanism is how shares of an ETF are created or redeemed as needed and thus is where there can be differences in what the value of the holdings can be versus the trading price. If the ETF is thinly traded, then the difference could be big as more volume would be where the mechanism could kick in as generally there are blocks required so the mechanism usually created or redeemed in lots of 50,000 shares I believe. From the link where AP=Authorized Participant: With ETFs, APs do most of the buying and selling. When APs sense demand for additional shares of an ETF—which manifests itself when the ETF share price trades at a premium to its NAV—they go into the market and create new shares. When the APs sense demand from investors looking to redeem—which manifests itself when the ETF share price trades at a discount—they process redemptions. So, suppose the NAV of the ETF is $20/share and the trading price is $30/share. The AP can buy the underlying securities for $20/share in a bulk order that equates to 50,000 shares of the ETF and exchange the underlying shares for new shares in the ETF. Then the AP can turn around and sell those new ETF shares for $30/share and pocket the gain. If you switch the prices around, the AP would then take the ETF shares and exchange them for the underlying securities in the same way and make a profit on the difference. SEC also notes this same process.",
"title": ""
},
{
"docid": "82163",
"text": "Not a good idea. When you form a partnership with someone that creates a legal connection between you two. What if he racks up $50,000 on the company credit card? Do you want to be responsible for that debt? A better way to do this would be to either charge your clients $X for IT work and pay him half of $X which would get you the same 50% or simply have him agree to share 50% of any income he gets from people referred by you. This can be done in a simple contract or agreement without force you both into a partnership.",
"title": ""
},
{
"docid": "473292",
"text": "\"Personally, I avoid making business deals with friends and relatives. There's just too much of a possibility that things can go wrong. Let's assume that you're honest people and you have no intention of cheating your mother-in-law. Still, all sorts of things could happen that could make it difficult for you to repay the loan. You could lose your job. You could get some big medical expense. Etc. Then what happens? Then your financial problems become family problems. There's a strong temptation when people borrow from relatives to make paying the loan the lowest priority in their budget. \"\"I know I promised to pay \\$X per month, but things are really tight right now and Mom should understand.\"\" Maybe she does understand and can manage without it. But maybe not. And then it becomes a family fight. \"\"You promised you'd pay it back.\"\" \"\"And we will, we're having a hard time right now. Can't you just give us a break?\"\" Etc. Or she might have some extra expense, and say, \"\"Hey, can't you pay a little more this month? I really need some extra cash.\"\" \"\"I'm sorry, we're struggling just to make the regular payments, we can't.\"\" \"\"Well I was willing to loan you all this money. The least you could do is pay me back when I need it.\"\" Etc. You can end up ruining family relationships over money. Your wife can find herself in the position of having to choose whether to side with her mother or her husband. Etc. I'm sure plenty of people do things like this and it works out just great. But there are big risks. And by the way, apparently this was your idea, not your mother-in-laws. I wonder what her reaction is. Is she eager to help out her daughter and son-in-law and had nothing in particular to do with the money anyway? Or is she feeling very imposed on? It's one thing to ask relatives to let you borrow their car for the weekend. Asking someone to loan you $50,000 is a very big request. If one of my kids asked me to loan them $50,000 from my retirement fund, I'd consider that a very presumptuous request. (Unless they needed the money for life-saving surgery for my grandchild or some such.)\"",
"title": ""
},
{
"docid": "228289",
"text": "Thanks for the feedback obelus, The cost is $20,000 to 50,000 sqft. Ya I am just looking for a rough idea of what a similar newer building is costing I figured what we are paying is really high as the building is extremely old and designated as a heritage site so we can't just knock it down. Beautiful building just not very efficient. The newer building is the route I think we are gonna end up going not sure what we can do with the current building as not too many options for resale. We can't adjust the lease rates to compensate for the cost as the tenants are all seniors and it is an integrated care home. A change to apartments would prove difficult as there are no kitchens in 90% of the suites. We are currently paying approximately $0.40 psf a month to heat (All electric) and the estimate for the new building is $0.1425 psf (Geothermal) so it is a pretty huge impact in comparison if it is possible but I haven't heard of a real building actually costing that little before. Thanks for the suggestion for the IR I think I am gonna get some one in after the holidays to do a inspection to see if there is any short term fixes we can do with our system.",
"title": ""
},
{
"docid": "137078",
"text": "\"Here's what's going to happen: At the last minute, he's going to \"\"discover\"\" that for some reason first you must send him $10,000. He'll tell you not to worry, as he's still going to send you $40,000... now $50,000. In fact, he's going to tell you that he'll send you $60,000 and tell you to keep the $10,000 as a \"\"finders fee\"\". Then you will send him, $10,000 and he will walk away with your $10,000. You'll never hear from him again. This is a very common scam. The best way to avoid it is not to tell him you won't do it for IRS reasons. The best thing to do is to stop accepting email from him and (optionally) report him to law enforcement.\"",
"title": ""
},
{
"docid": "17801",
"text": "If you deposit an amount greater than S$50,000, it's only insured up to S$50,000. In the event that the bank fails or is declared insolvent, the SDIC will pay deposit holders their total balance in all accounts with that bank, up to S$50,000 in aggregate per depositor per Scheme member by law. In other words SDIC will only pay S$25000.00 and not S$50000.00, even though your deposit with that bank is insured up to S$50000.00 Please clarify this point as most banks are unaware of this aspect of the payout.",
"title": ""
},
{
"docid": "103584",
"text": "\"I think you might be asking the wrong question. You have plenty of capital on the side that can be invested. Instead of asking whether you should get an adviser, you might want to examine what your end goal is. Are you looking to build long term growth of you capital? Are you asking about and adviser because you don't want to handle your money, or is it simply because \"\"that's what people do?\"\" I would imagine that the answer to 1. is yes and that the answer to 2. is that you want to handle your money, and you always considered this something best left to the advisers. I shall proceed on these hypothetical assumptions. In my humble opinion, I would do the following: Skip the adviser and the fees that go with it. For a young professional like yourself, especially with an engineering background, you can certainly handle the education required to learn the mechanics of investing. Invest some time to learn the fundamentals of the market such as asset classes, basic terminology ect. You will benefit in several ways. For one, you will learn an invaluable skill and save tens of thousands in fees during your lifetime. Moreover, you will have complete control of your risk profile, allocation, and every penny that belongs to you. I really am not bashing advisers, but no one will care as much about your money as you will. And don't be fooled. The market is efficient. An adviser does not have any more edge in a market than anyone else. And from first hand experience, they rarely outperform benchmarks net of fees. I assume you have made it to this step because you want to manage your own money and financial future. Sounds scary, how should one proceed? Let's assume that $100,000 is \"\"in play\"\". And since you are learning the ropes, let's leave $50,000 in cash for now. This leaves $50,000 to start a portfolio. I'd start by building a core position of all the major asset classes in ETF form. This means buying things like SPY or TLT. If you're comfortable, you can start selling monthly calls against these positions to reduce basis and earn some income. The point is, your only limitation at this point is taking time to learn the ropes. The technology is there, the free education is there, and liquidity and product mix is there. Next thing you know you're learning how gamma scalping works, or maybe you're more of a Buffett type. This is how I view finance in general, and truly hope you break through the initial barrier to controling your own finances.\"",
"title": ""
},
{
"docid": "365285",
"text": "Rule of thumb: To retire with a yearly income of $X, you need to save $(20*X) -- in other words, the safe assumption is that you'll average 4% returns on your stabilized savings/investments. In the case of retiring with a $50k passive pretax income, that means you need savings of $1M by the time you retire. If you want the $50,000 to be real post-tax spendable dollars, and your savings aren't in something like a Roth 401k or Roth IRA, increase that proportionately to account for taxes. How you get there depends on what you start with, how much you put into it every year, how you invest it and how many years you have before your retirement date. Passive investment alone will not do it unless you start with a lot of money; passive ongoing investment may depending on how much you can make yourself save when. To find out whether any specific plan will do what you need, you have to work with real numbers.",
"title": ""
},
{
"docid": "194030",
"text": "\"Why do people keep talking about 401K's at work? That is NOT dollar cost averaging. DCA refers to when you have a large sum of money. Do you invest it all at once or spread it out over several smaller purchases over a period of time? There really isn't a \"\"when\"\" should I use it. It is simply a matter of where your preferences lie on the risk/reward scpectrum. DCA has lower risk and lower reward than lump sum investing. In my opinion, I don't like it. DCA only works better than lump sum investing if the price drops. But if you think the price is going to drop, why are you buying the stock in the first place? Example: Your uncle wins the lottery and gives you $50,000. Do you buy $50,000 worth of Apple now, or do you buy $10,000 now and $10,000 a quarter for the next four quarters? If the stock goes up, you will make more with lump-sum(LS) than you will with DCA. If the stock goes down, you will lose more with LS than you will with DCA. If the stock goes up then down, you will lose more with DCA than you will with LS. If the stock goes down then up, you will make more with DCA than you will with LS. So it's a tradeoff. But, like I said, the whole point of you buying the stock is that you think it's going to go up! So why pick the strategy that performs worse in that scenario?\"",
"title": ""
},
{
"docid": "239064",
"text": "When I invest in a business valued at $50,000, I pay $25,000 and receive 50% equity. Does that $25,000 go to the current owner of the business, or into the capital of the business itself? Who receives the money depends on who is selling you the equity. There are a couple of different scenarios that can fit your question. You could buy existing shares from the current owner(s) of the company. In this case, the current owner(s) would be receiving the funds from you, and in return giving you their stake in the company. So if you all agree that the value of the business is $50,000, and you give $25,000 to the current owner(s), they give you half of their shares. The value of the company has not changed. The company could be issuing new shares. This is called stock dilution, or an increase in authorized share capital. Let's say that everyone agrees that the value of the business is $50,000. The company could create new shares and sell them to you for $25,000. In this case, the value of the company has jumped to $75,000; you now control one-third of the company, and the existing owner(s), who previously owned 100% of the company, now only own two-thirds. In order for you to end up with 50% of the company in this case, you would have to invest $50,000 instead, which would result in the company being valued at $100,000. If you are wondering why the current owners would agree to this second scenario, there are two questions that address this:",
"title": ""
},
{
"docid": "144313",
"text": "Generally it is advisable to mention what country you're asking about, as tax laws differ. To the best of my knowledge, however, this particular issue is handled consistently in every tax jurisdiction I'm familiar with. You invested X, it appreciated and is now worth X + Y. In your example, X = $10,000 and Y = $40,000. Total X + Y = $50,000. When you withdraw an amount, say A (in your example A = $10,000), it is considered a withdrawal of both the earnings and the original capital, in proportion to the total of your account. Taxable portion of the withdrawal is proportional to the earnings. Lets mark it T. In your example, T = $10,000 - $10,000 * $10,000/$50,000 = $8,000. I.e.: 80% of the withdrawal will be attributed to earnings and would be taxable (short term in your case, if you're in the US), and 20% to the original capital. This will keep the proportion of the remained the same - 20% of the remaining amount will be attributed to the original capital (accidentally, it will be $8,000), and the remaining 80% will be attributed to the earnings. The withdrawn amount attributed to the capital ($2,000), and the remaining amount attributed to the capital ($8,000) will equal exactly to the invested amount.",
"title": ""
},
{
"docid": "267901",
"text": "\"These agencies consolidate your debt and make it an easy monthly instalment for you. They also try to negotiate with credit cards. They do so for a fee. Other option is to not pay the debt. During this time , expect credit cards to keep sending you bills and reminders and ways to contact you. Once it is not paid for a significant amount of time ( 18 months ) , the lender will \"\"sell\"\" your debt to a collection agency. You will start getting bills from collection agencies. Collection agencies can settle for up to 40 % of the actual debt. So if you had 5 credit cards , you would have 5 different collection agencies trying to get in touch with you. You can call them and tell them that you cannot pay the full amount. They will offer you settlements which you can accept or decline. The longer the unpaid debt , the more the discount they will offer. One very important thing to remember is that the unpaid amount will be sent to you on a 1099-c form . This means you have to recognize this as income. It is applicable to the year when the debt is settled. In a nut shell , you owe 120,000. You don't pay. Credit cards keeps calling you. You don't pay. After 12-18 months , they handover your debt to collection agencies. Collection agencies will try to get in touch with you. Send you lawsuit letters. You call and settle for say 50,000. You pay off 50,000 in 2016. Your debt is settled. But wait you will get 1099-C forms from different agencies totaling 70,000 ( unpaid debt ). You will have to declare that as income and you will owe tax on that. Assuming say 30 % tax you will have to pay up 21,000 as tax to IRS assuming no other income for simplicity. SO what you did was pay up 50 + 21 = 71,000 and settled the debt of 120,000. Your credit score will be much better than if you never paid at all.\"",
"title": ""
},
{
"docid": "333961",
"text": "\"Trying to \"\"time the market\"\" is usually a bad idea. People who do this every day for a living have a hard time doing that, and I'm guessing you don't have that kind of time and knowledge. So that leaves you with your first and third options, commonly called lump-sum and dollar cost averaging respectively. Which one to use depends on where your preferences lie on the risk/reward scpectrum. Dollar cost averaging (DCA) has lower risk and lower reward than lump sum investing. In my opinion, I don't like it. DCA only works better than lump sum investing if the price drops. But if you think the price is going to drop, why are you buying the stock in the first place? Example: Your uncle wins the lottery and gives you $50,000. Do you buy $50,000 worth of Apple now, or do you buy $10,000 now and $10,000 a quarter for the next four quarters? If the stock goes up, you will make more with lump-sum(LS) than you will with DCA. If the stock goes down, you will lose more with LS than you will with DCA. If the stock goes up then down, you will lose more with DCA than you will with LS. If the stock goes down then up, you will make more with DCA than you will with LS. So it's a trade-off. But, like I said, the whole point of you buying the stock is that you think it's going to go up, which is especially true with an index fund! So why pick the strategy that performs worse in that scenario?\"",
"title": ""
},
{
"docid": "223167",
"text": "I can only give you advice on what I would do if I was in this situation: As mbbhunter mentions above, the first question you have to ask yourself is how much time do you want to spend to manage your money? The more money you have, the more money you can possibly make by becoming educated in investing (e.g. if you can increase your return on investment (ROI) on $500,000 1%, it does a lot more than increasing your ROI on $50,000 by 1%. If I was you, I would either track my investments myself or ask an accountant (or a fee-only financial advisor) to determine 3 things: At the very least I would spend some serious time getting educated about your newfound wealth. Good luck and if you find a need for additional computer programmers at your company dont hesitate to let me know ;-)",
"title": ""
},
{
"docid": "443960",
"text": "\"Even though this isn't really personal finance related I still feel like there are some misconceptions here that could be addressed. I don't know where you got the phrase \"\"pass-through\"\" insurance from. What you're describing is a self-funded plan. In a self-funded arrangement an employer contracts a third-party-administrator (TPA), usually one of the big health insurance carriers, to use it's provider network, process and adjudicate claims, etc. In addition to the TPA there will be some sort of stop-loss insurance coverage on each participant. Stop-loss coverage usually provides a maximum amount of risk on a given member and on the entire population for a given month and/or year and/or lifetime. The employer's risk is in between the plan deductible and the stop loss coverage (assuming the stop-loss doesn't have a maximum). Almost all of the claim dollars in a given plan will come from very very few people. These costs typically arise out of very unforeseen diagnoses not chronic issues. A cancer patient can easily cost $1,000,000 in a year. Someone's diabetes maintenance medicine or other chronic maintenance will cost no where near what a botched surgery will in a year. If we take a step back there are really four categories of employer insurance. Small group is tightly regulated. Usually plan premiums are filed with a state authority, there is no negotiating, your group's underwriting performance has zero impact on your premiums. Employers have no way of obtaining any medical/claim information on employees. Mid-market is a pooled arrangement. The overall pool has a total increase, and your particular group performs better or worse than the pool which may impact premiums. Employers get very minor claims data, things like the few highest claims, or number of claims over a certain threshold, but no employee specific information. Large-group is a mostly unpooled arrangement. Generally your group receives it's own rating based on its individual underwriting performance. In general the carrier is offloading some risk to a stop-loss carrier and employer's get a fair amount of insight in to claims, though again, not with employee names. Self-funded is obviously self-contained. The employer sets up a claims checking account. The TPA has draft authority on the account. The employee's typically have no idea the plan is self funded, their ID cards will have the carrier logo, and the carrier deals with them just as it would any other member. Generally when a company is this size it has a separate benefits committee, those few people will have some level of insight in to claims performance and stop-loss activity. This committee will have nothing to do with the hiring process. There are some new partially self-funded arrangements, which is just a really low-threshold (and relatively expensive) stop-loss program, that's becoming somewhat popular in the mid-market group size as employers attempt to reduce medical spend. I think when you start thinking on a micro, single employee level, you really lose sight of the big picture. Why would an employer hire this guy who has this disease/chronic problem that costs $50,000 per year? And logically you can get to the conclusion that with a self-funded plan it literally costs the company the money so the company has an incentive not to hire the person. I understand the logic of the argument, but at the self funded level the plan is typically costing north of half a million dollars each month. So a mid-level HR hiring manager 1. isn't aware of specific plan claims or costs and is not part of the benefits executive committee, 2. won't be instructed to screen for health deficiencies because it's against the law, 3. a company generally won't test the water here because $50,000 per year is less than 1% of the company's annual medical expenses, 4. $50,000 is well below the cost to litigate a discrimination law-suit. Really the flaw in your thought process is that $50,000 in annual medical expense is a lot. A harsh child-birth can run in the $250,000 range, so these companies never hire women? Or never hire men who could add a spouse who's in child bearing years? Or never hire women who might have a female spouse who could be in child bearing years? A leukemia diagnosis will ratchet up $1,000,000 in a year. Spend a bit of time in intensive care for $25,000 per day and you're fired? A few thousand bucks on diabetes meds isn't anything relative to the annual cost of your average self-funded plan. The second flaw is that the hiring managers get insight in to specific claims. They don't. Third, you don't hand over medical records on your resume anyway. I typed this out in one single draft and have no intention of editing anything. I just wanted paint a broad picture, I'm sure things can be nit-picked or focused on.\"",
"title": ""
},
{
"docid": "336011",
"text": "\"No. The more legs you add onto your trade, the more commissions you will pay entering and exiting the trade and the more opportunity for slippage. So lets head the other direction. Can we make a simple, risk-free option trade, with as few legs as possible? The (not really) surprising answer is \"\"yes\"\", but there is no free lunch, as you will see. According to financial theory any riskless position will earn the risk free rate, which right now is almost nothing, nada, 0%. Let's test this out with a little example. In theory, a riskless position can be constructed from buying a stock, selling a call option, and buying a put option. This combination should earn the risk free rate. Selling the call option means you get money now but agree to let someone else have the stock at an agreed contract price if the price goes up. Buying the put option means you pay money now but can sell the stock to someone at a pre-agreed contract price if you want to do so, which would only be when the price declines below the contract price. To start our risk free trade, buy Google stock, GOOG, at the Oct 3 Close: 495.52 x 100sh = $49,552 The example has 100 shares for compatibility with the options contracts which require 100 share blocks. we will sell a call and buy a put @ contract price of $500 for Jan 19,2013. Therefore we will receive $50,000 for certain on Jan 19,2013, unless the options clearing system fails, because of say, global financial collapse, or war with Aztec spacecraft. According to google finance, if we had sold a call today at the close we would receive the bid, which is 89.00/share, or $8,900 total. And if we had bought a put today at the close we would pay the ask, which is 91.90/share, or $9190 total. So, to receive $50,000 for certain on Jan 19,2013 we could pay $49,552 for the GOOG stock, minus $8,900 for the money we received selling the call option, plus a payment of $9190 for the put option we need to protect the value. The total is $49,842. If we pay $49,842 today, plus execute the option strategy shown, we would have $50,000 on Jan 19,2013. This is a profit of $158, the options commissions are going to be around $20-$30, so in total the profit is around $120 after commissions. On the other hand, ~$50,000 in a bank CD for 12 months at 1.1% will yield $550 in similarly risk-free interest. Given that it is difficult to actually make these trades simultaneously, in practice, with the prices jumping all around, I would say if you really want a low risk option trade then a bank CD looks like the safer bet. This isn't to say you can't find another combination of stock and contract price that does better than a bank CD -- but I doubt it will ever be better by very much and still difficult to monitor and align the trades in practice.\"",
"title": ""
},
{
"docid": "314850",
"text": "In the UK I believe the first £50,000 in each bank are secured by the government, so are very safe but one has to check what 'each bank' means as some are members of the same 'group'. See the FSCS",
"title": ""
},
{
"docid": "119456",
"text": "Are you saying that you did not tell your employer, more specifically, your payroll department, that you got married, via a W4? The W4 does not say '25%' bracket, but it asks for how many withholding allowances you plan to take. In effect, you are withholding at the single rate, but are married now. When you do your taxes for 2013, you'll see the full effect of what the W4 has on your withholding. I suggest you use this time to update the W4, and not lend money to Uncle Sam. Here's the current tax table from FairMark Publishing. 2013 gives a single a combined $10K in standard deduction and exemption, with a couple getting $20K. For a simple return, this is the info you need to figure out what you'll get back, and conversely, how much to pay next year. e.g. a gross of $50,000 - for single the tax is on $40,000. $5929. For a couple, $30K taxable is a tax of $3608. On a side note - I strongly recommend Roth accounts when in the 15% bracket and shift to Pre-Tax accounts as you get into the 25% bracket.",
"title": ""
},
{
"docid": "197273",
"text": "As you can see by his username this guy works in IT. I will explain for those who aren’t in the industry. In IT demand for employees has never been higher. It is crazy right now. This means it is hard to get talent, particularly good talent which can be many times more productive than bad ones. Now Amazon is a tech company fundamentally. What many may not realize is Amazon is also the world’s largest hosting platform too. For example, Reddit and Netflix are on their systems. So they aren’t just a store, they do a lot of everyone else's tech too. This means they need a shit-tonne of good tech and related people. So the location will likely hinge on where the can find good staff. However, as OP just said Amazon has a terrible reputation in the industry. So this makes this even more difficult as everyone hates them and no one will move for them, and they need a lot of good people which are in high demand elsewhere. This is what their decision will rest on. Tax breaks and all are perks, but they need to find 50,000 experienced employees to fill this thing, everything else is secondary.",
"title": ""
},
{
"docid": "85373",
"text": "If you plan to keep this asset for ten years then you can take the deprecation of its cost over that time period. For simplicity lets treat that as 120 monthly payments. So at a purchase price of $60,000 you are committing around $500 per month not including vehicle maintenance. I typically allocate around 20 percent of the purchase price of my vehicles for future maintenance costs. Since you have the cash to purchase this outright you have an option not afforded to most people. This adds for additional consideration. Here is an example. You purchase a $60,000 car and put $10,000 down. You finance $50,000 at 2.84% over 60 months. Your total finance cost is $53,693 if you do not miss any payments. The question here is can you make more than $3,693 on the $50,000 that you would retain in this situation over a five year period? I know that I most certainly can and is an excellent example of why I finance my vehicles. Obviously this all goes out the window if you do not have the credit for top rates. I have also negotiated a vehicle maintenance plan with the dealership at the time of my vehicle purchases. Most dealerships offer this service, the key here is negotiating. On my last truck I was able to get an all inclusive maintenance policy for 72 months for 8% of the purchase price. Your mileage will vary with manufacturer and dealership. As described in the comments above it is never beneficial for an individual to lease. You end up paying more for the newer models. I consider that to be a lifestyle choice as it is most certainly not a sound financial decision.",
"title": ""
},
{
"docid": "95282",
"text": "\"Contribute as much as you can. When do you want to retire and how much income do you think you'll need? A $1M portfolio yielding 5% will yield $50,000/year. Do some research about how to build a portfolio... this site is a good start, but check out books on retirement planning and magazines like Money and Kiplinger. If you don't speak \"\"money\"\" or are intimidated by investing, look for a fee-based financial advisor whom you are comfortable with.\"",
"title": ""
},
{
"docid": "69087",
"text": "\"Yeah... I think what's missing here is that Amazon is an ABSOLUTE last resort place to work. After my experiences with them, I would just leave the industry and go hang drywall before I'd work there. There's a lot getting lost in this \"\"50,000 jobs\"\" thing- these aren't shovel ready jobs, these are jobs that Amazon would likely just NOT FILL if they couldn't find exactly the right people. The AVERAGE tenure for an Amazon engineer is ONE YEAR. People hate working there, and nobody plans on staying long. They are the most dangerous and toxic workplace in the country right now, and whatever formula they have for extracting value from human misery had better stay locked up in the vault with the KFC recipe, or everyone in this business is screwed. This is where you go work for a year after school, get burnt, and use the skills to go find a better place to work. Think FoxConn, not \"\"cool startup with perks\"\". There ARE some cities who could benefit from this, but I think they're the least likely to get this. So far California offers the best mix of talent and tax incentives so far, IMO. Whoever gets this will probably not benefit, in any way. That's how Bezos operates. This will flood your city with 50,000 dumb ass 22 year olds who don't care about spending 60% of the income on rent(because this is the first time they've paid it!), don't have time for life outside of work, and who plan on quitting when the lease is up. If you're an Uber driver of a Condo tower builder, you'll benefit.\"",
"title": ""
}
] |
6610
|
As a parent of a high school student, what should my short-term cash policy be to optimize my college costs?
|
[
{
"docid": "597627",
"text": "\"There is no simple answer to your question. It depends on many things, perhaps most notably what college your daughter ends up going to and what kind of aid you hope to receive. Your daughter will probably fill out the FAFSA as part of her financial aid application. Here is one discussion of what parental assets \"\"count\"\" towards the Expected Family Contribution on the FAFSA. You can find many similar pages by googling. Retirement accounts and primary residence are notable categories that do not count. So, if you were looking to reduce your \"\"apparent\"\" assets for aid purposes, dumping money into your mortgage or retirement account is a possibility. However, you should be cautious when doing this type of gaming, because it's not always clear exactly how it will affect financial aid. For one thing, \"\"financial aid\"\" includes both grants and loans. Everyone wants grants, but sometimes increasing your \"\"eligibility\"\" may just make you (or your daughter) eligible for larger loans, which may not be so great. Also, each college has its own system for allocating financial aid. Individual schools may ask for more detailed information (such as the CSS Profile). So strategies for minimizing your apparent assets that work for one school may not work for others. Some elite schools with large endowments have generous aid policies that allow even families with sizable incomes to pay little or nothing (e.g., Stanford waives tuition for most families with incomes under $125,000). You should probably research the financial aid policies of schools your daughter is interested in. It can be helpful to talk to financial aid advisors at colleges, as well as high school counselors, not to mention general financial advisors if you really want to start getting technical about what assets to move around. Needless to say, it all begins with talking with your daughter about her thoughts on where to go.\"",
"title": ""
}
] |
[
{
"docid": "576897",
"text": "\"Now asking if college is worth it? That's not the question that should be asked. Higher education and extended training are always a benefit at any point in life when it's of high quality. The question that should be asked is, \"\"why is the cost of college as high as it is?\"\" When I went to college to get my Bachelors, a semester at my state university cost $940 bucks US (this was in the early to mid 90s). Twenty years later, that same education cost $6,500 per semester. The main difference between these periods is that borrowing for school is now standard practice (much less so in the 90s). Any time you need to borrow to pay for something, you're going to overpay just because you have access to credit and can keep borrowing when someone hands you a bill. Today, kids borrow for college because they don't have much choice if their parents didn't save enough or stopped supporting them right out of high school. And if you have this level of debt right out of college, your hands will be tied for decades - it affects things like first home buying and disposable income spending. The only way to drive the cost of college down is to plan ahead and pay with cash - and to do that, you need to have enough luck to be born to parents who care enough to help with your future. If schools know you can't or won't borrow to pay for an education, they adjust.\"",
"title": ""
},
{
"docid": "264400",
"text": "\">> I propose to make the requirements for finish high school and college degrees much much higher, as it was in the past. > Not gonna happen. Totally agree with you! What I was proposing is what SHOULD be done. > waiting for disadvantaged kids to get higher scores will not happen until they get accepted into college. Even then! Almost all disadvantaged kids, smart or not smart, the diploma they get is almost worthless. The diploma will not give them much advantage or improve their situation. The diploma barely even helps very smart kids from rich advantaged homes. Actually, if in the past, no matter who you knew, no matter your family background, a diploma will almost always GUARANTEE a secure and advantaged life. > If you force schools to gain their income from future students earnings they will have high concern for kids that have a good P/E ratio. It will also stop the loan industry from putting these kids into debt. In theory, you are correct. In practice, many many problems to implement. For starters, this makes college a very risky business because it's very hard to predict future income of its students, even the very smart and accomplished students. And I will give you a related example: colleges teach Computer Science (Programming) to many kids today, but the profession is about to die due AI and automation + outsourcing. This was unexpected 1-2 years ago. Barely economists can predict the economy, so you want colleges to predict income based on what is taught? > The downside is that it may turn colleges into trade techs, Actually, colleges are already trade techs because, today, almost all students study just(!) for the hope to get a job. In the past, you studied to become a scholar and wise, and then pick some kind of a job of your interest where being generally smart and knowledgeable is needed. BOTTOM LINE: Since you and I know that nothing will be done, no higher standards and no future-income based tuition, here's what what's happening with my son, which is what happened with me, which is still happening in Germany. No, I am not German, but I come from a German culture - my parents are of German descent, but I was born and raised in Israel. It's called \"\"Master and Apprentice\"\". I have been working since I was 13, with computers, and if you consider my age (55), when I was 13, no PCs with internet, and only punch cards were used to access a computer. My parents did not push me... it was me who felt the need to work, while I was studying (just like my father had that need when he was young). My son, 13 today, but since he was 10, the apple does not fall far from the tree, found work (he's not even allowed to work by law) and is making money. He's right now teaching, administering and designing Minecraft \"\"worlds\"\" and applications. **Hands on experience, especially taught from a Master is better than any Diploma!!!!** He will probably go to some so-so college to get a piece of paper called \"\"Diploma\"\" WHILE he will continue working in whatever he's interested. He will be successful like I am (not trying to brag). I never pushed him, but I explained to you some realities of the world. LAST WORD: actually, most Masters, real Masters, are desperate to teach, for free, their knowledge, vision and know. And the system does not allow them to do that, to protect the colleges and universities. Only in Medicine, it's still happens. Think about it!!!!!\"",
"title": ""
},
{
"docid": "482972",
"text": "As a parent, I call bullshit on this. I may or may not retire rich, but my kids will have more opportunity than I did, and they will have the benefit of learning what I have learned about entrepreneurship, what my wife has learned about medicine, about what we both have learned about health, debt, relationships, sleep, cooking, self reliance, and so on. We are the first generation in each of our families to be upper middle class, none of our parents had college degrees. Our kids go to better schools than we did, and will have more opportunities than we did. If they take advantage of them, they will be more successful than we are. This is not luck. This is by design, because we don't think of the well-being of our kids and future grand kids and future great grandkids in terms of our current income or our own lifetimes. We don't buy the most expensive cars or houses or clothes we can. We save, invest, pay down debt incurred from mortgage and student loans before we knew better, put money into a future for our children. Us focusing our entire lives from the day we graduated from high school with no money and no job up until now, and into the future, has been and will be geared toward making sure my future family has it better than I did or my parents did. Sure, we are lucky enough to have been born now in America and not to have been tragically murdered or disabled, and lucky enough to have had roads and access to public school, but to say my family is simply lucky is horseshit. We are very fortunate and it is important to be grateful for the luck we have had, but decades of focus and sacrifice and dedication with a specific focus on increasing income and saving cannot be dismissed, and a dynastic focus on generational wealth building simply cannot be called only luck.",
"title": ""
},
{
"docid": "58774",
"text": "\"My parents and I were suckered into buying this kind of thing when I was in high school. The sales people literally told us that it could be used to pay off student loans - they left out the \"\"in the event of your death\"\" part. We knew it was a life insurance policy, but were told that it would \"\"mature\"\" 6 months after graduation from college, and that it would then be disbursed to pay off loans, even if I didn't die. That seemed strange to us, so we explicitly asked several different ways whether it would pay off the loans after graduation, even if I lived, and they just straight up told us, \"\"Yes.\"\" I'm guessing this ploy is still being used. Also, last I checked, student loans are non-transferable in the unfortunate event that your child dies - which means the loan is forgiven anyway - so this whole thing seems like garbage to me, at least in the student loan sense. I would steer clear from this stuff - it's pure snake oil in my experience.\"",
"title": ""
},
{
"docid": "205772",
"text": "The main problem is that everyone graduates from high-school, almost everyone gets accepted to college and almost nobody who put minimum efforts fails college classes. I know that! I was an adjunct professor and was told I can't fail my students except in extreme cases. In the past, to graduate from high school was a hard accomplishment. Getting accepted to college was a hard accomplishment. Surviving the first year in college was an accomplishment and getting a degree was an accomplishment. Those accomplishments in the past gave you excellent benefits! Benefits of assured respected jobs, income, security, and being the exception. An example: in the past, to be a teller in the bank, you did not have to finish high-school, just be good in basic math. Today: a teller in the bank, one of the lowest paying jobs you can find, requires a Bachelor degree. Does the bachelor degree worth it? **Basically, higher education became an industry, that accept as many people as possible, charge them as much as it can, give degrees to undeserving people, and those degrees are almost worthless. You can't do much with a Bachelor degree!** The solution is to make the standards for high school and college much higher. Everything will fall into place then. Fewer students who are actually interested in studies and are qualified for their studies will mean better teaching, lower costs, and much better benefits for those deserve those benefits. Chances of this happening? Big big zero. Actually, the chances of even lower standards for colleges and schools are 100%. So, for my son, I explained to him to not invest much in an excellent and expensive college for [worthless] degrees. Instead, while he studies, work in the area he is interested in and learn from the masters he works with. My son is 13, but since being 11, he works (yes, he makes money) with some computer system he's interested in. Personally, I worked since I was 13, study and worked all the time, got my Bachelor and Masters, and I am doing extremely well. I get paid for what I know, which Zero of it came from my studies and money I spent in those studies.",
"title": ""
},
{
"docid": "119117",
"text": "\"Is a student loan a type of loan or just a generic name used to refer to a loan for someone who is going back to school? A student loan from the federal government is a specific type of loan used for education purposes (i.e. attending college). They have guidelines associated with them that are very flexible as compared to a student loan from a private bank. If a student loan is a different type of loan, does it only cover the costs of going to the school? Every student at a university has a \"\"budget\"\" or the \"\"cost of attendance\"\". That includes direct and indirect costs. Direct costs are ones billed directly to you (i.e. tuition, room and board - should you choose to live on campus, and associated fees). Indirect costs are such things like books, travel expenses (if you live out of state), and personal things. Direct costs are controlled by the school. Indirect costs are estimated. The school will usually conduct market research to determine the costs for indirect items. Some students go above that, and some go below. For example, transportation is an indirect cost. A school could set that at $500. There are students who will be above that, and some below that. If you choose not to live on campus, then rent and food will become an indirect cost. Student loans can cover up to 100% of your budget (direct and indirect added together). If your total budget is $60,000 (tuition, room and board, transportation, books, supplies, etc.) Then you are able to borrow up to that amount ($60,000). However, because your budget is both direct and indirect costs, you will only be billed for your direct costs (tuition, etc.). So if your direct costs equal $50,000 and your student loan was certified for $60,000, then you will get that $10,000 back in the form of a refund from the school. That does not mean you don't have to pay it back - you still do. But that money is meant for indirect costs (i.e. books, rent - if you're not staying on campus, etc.). If your school is on semesters vs quarters, then that amount is divided between the terms. Summer term is not factored in, that's another process. Also with student loans, there are origination costs - the money associated with processing a loan. A good rule of thumb is to never borrow more than you need. Source: I used to work in financial aid at my college.\"",
"title": ""
},
{
"docid": "223896",
"text": "\"As a former professor, I have few questions: 1. When it comes to the things you listed, how to **filter** things, how to **build a structure and methodology** to handle tasks, how to **research and elaborate** on the knowledge needed, **motivation**, **social and personal traits**, and seeking **feedback** (including self-critic), what percentage of this is taught or can be taught in school, and what percentage of this is part of the personality you already have and cannot be taught? Can \"\"motivation\"\", for example, be taught in school? 2. When it comes to practical and current knowledge needed in the workplace, is it coming more from what was taught in college, or is it more from self study and experience gained in the first few weeks at a real work environment? 3. Do colleges and universities fail students when needed? When I was teaching, and from professors I currently know, the guidelines are very strict as for the possibility of failing a student. Few of my students should never ever be accepted to college, definitely should have failed my classes as clearly they do not have the capability to handle the real requirements, bad and immature personalities, zero chance to improve, etc. I was prevented from failing few of them. Lastly, I do think kids should go to college, but traditionally, colleges and universities were mostly(!) to demand high standards, tough acceptance, and fail those who can't handle the requirements. Thus, those fewer who got degrees deserved those degrees and almost always benefited from those degrees as for getting work, good compensation for their work and succeeding in their work.\"",
"title": ""
},
{
"docid": "121072",
"text": "I'm sorry, I didn't realize you served. Congrats on getting your government to help you out with your degree. As for me, I've deleted my comment and am answering with a throwaway because I don't want this to be tied to my persona in any way because of the following. Much like I didn't know shit about you, you don't know shit about me. I was born in a shithole country you've never heard of. My grandparents were collective farmers with barely a primary school education and my parents grew up on those farms and didn't go to college. My father was persecuted by the government and thrown in jail when I was four and stayed there until I was 10 – thankfully my mom and I managed to move to a Western country, where we lived on government subsistence and with no family within 3000km, because they're all (still) living in such shithole countries. We came into money once he got released and I reached high school age and hence the what you qualify as lavish, jealousy-inducing lifestyle, but even then despite the expensive private school (which sends one kid to an ivy every two years), plushy vacations and nice clothes I had to hustle entirely by myself to get into good schools in the US. Nobody in my entire extended family had ever gone on to tertiary education in any country, let alone the most competitive one in the world. Despite ready access, I took on no standardized prep tutors (got a 35 – fuck the people saying high score = expensive tutors), no after school help, no expensive college app packaging. I didn't even use my story as a college essay (in fact, nobody knows, not even my closest friends [they just think I'm some rich kid, much like you]) because I don't think the circumstances I was born with (and, alternatively, was blessed with afterwards) allow me special privileges or empathy in any way. The amount of effort I can put into my life solely depends on me, not my environment. And now that I'm here it could all come crashing down any second because my shithole country could decide to take it all away again. My parents can't even visit me in the US (hence the frequent flyer status you motherfucker) and who knows if I'll be able to finish my expensive program here while on a student visa – hence finance. I also find the American adoration of military service adorable when in so many countries (including mine) it's mandatory and a simple way of life, but I'm not going to argue with you on that because I realize it's a sensitive subject for you lot and I still respect your decision.",
"title": ""
},
{
"docid": "458535",
"text": "I think you have already outlined for yourself most of the pros and cons of each method of giving. It sounds to me like you have some desire to control how the money is spent, or at least reserve the right not to give it to a child who will waste it (according to your definition). If you set up an UTMA/UGMA account, or just give the money directly each year as a birthday gift, you are surrendering control of the money. It's a gift and is no longer yours to direct. If you set up a 529, you at least restrict the money to a particular, useful purpose. Moreover, if you retain ownership of the 529, you can take the money back, albeit with a tax penalty to yourself. If you do hold a 529 in your name, but for a child's benefit, there are a couple of things to consider with respect to future financial aid (this is from recent experience--my in-laws have 529s for our children, both of whom are currently in college). A 529 not owned by the student or the student's parent is not reported as an asset (of the child or the parent) on the Free Application for Federal Student Aid (FAFSA). However, once such a 529 is used to pay college expenses, the amount of those payments does get reported on the following year's FAFSA, and counts as untaxed income for the purposes of figuring the Expected Family Contribution (EFC). Untaxed income is assessed towards the EFC at 50%. In contrast, parental assets are assessed at around 7%, if I recall correctly, and student assets at around 35%. Student-owned 529s are assessed at the rate of parental assets, which is an advantage. If the amount you will set aside is less than the cost of one year of college, you can avoid the disadvantage of the untaxed income assessment by just using the entire 529 for the final year of school, since there will be no FAFSA for the following year. It occurs to me that there is one other way you can give to them that you did not mention, and may make you more comfortable in terms of encouraging some positive behavior. Namely, save the money in a self-owned account, then, when they are old enough to get a job that provides a W-2 showing declared, earned income, you can use the savings to fund a Traditional or Roth IRA for them, up to the limit allowed each year, until the money you set aside is exhausted. The Roth is a better long-term savings vehicle, but the Traditional would carry bigger penalties for early withdrawal and would therefore be less tempting to draw on.",
"title": ""
},
{
"docid": "411686",
"text": "While not entirely untouchable, a college fund can also be in the form of an Indexed Universal Life (IUL) contract through a life insurance agent. These often net a higher rate of return annually than any savings account, are not going to tank if the market does, and can be owned by you for the child. If no one else is on the policy, they have no access to it. You can name yourself the beneficiary as well. There's several very nice features to doing your child's college funding this way. You can ask that the contract is established for maximum cash value. This means the death benefit isn't the overriding need so the premiums you pay fill the cash value of the contract much more quickly. As mentioned in point 1., the contract has a death benefit. No other savings device will grant you this. Heaven forbid the child passes while you are saving for college. Now you will have a tax free benefit that will pay for burial and other related costs and can be used to fund yet another IUL policy if you have more than one child. Unlike other policies, you can set your minimum monthly premium and have the flexibility to add as much as you would like to fill the fund faster if you happen to come into more money and you want to direct it to that contract. There are ceilings to this so that you don't create a modified endowment contract (MEC. Look this up at investopedia), but this is specifically stated in your illustration so that you can keep your contributions a penny under that limit. Unlike college loans, you have extremely quick access to the funds when you need them (probably counter-intuitive to your desire for untouchable money). This can be achieved a couple of ways. You can borrow money from the insurer using your IUL cash value as collateral. Often, a check can be cut within 48 hours. This eliminates the time a normal lender takes in making the loan decision. Or, you can surrender the policy and take the cash value (paying taxes on your gains). The first keeps the policy in force while you pay back the loan if you desire. The second cancels the policy so that you can take your own accumulated money out. Utilizing an IUL in this manner can (but not always) lower your Expected Family Contribution (EFC) with colleges so that you could qualify for higher student aid. If your income puts you in the middle class, you would be wise to note this in particular. Having control over your EFC is major benefit. (If you'll read the link above, you notice the UGMA isn't necessarily the best idea as schools look to the student to give a higher percentage of their own assets than the parent.) Ultimately, while the IUL is a little known method for saving for college (and some will argue what they may) it would benefit you to speak with an insurance professional about this option. Ask if the insurer has access to the SAGE Rewards program (https://secure.tuitionrewards.com/). The program is a free benefit if you purchase a cash value contract like an Indexed Universal Life policy and activates IF the agency participates. The child earns tuition credits for every birthday of your child (not retroactive) and for having the policy. If you do an annual review, you earn more tuition credits. I have established these for clients and some have sent their child to college with more than 44k in college funding (split out over four years). The point system is 1 credit = 1 tuition dollar. Quite unlike air miles! For those of you reading this that have similar concerns, please consult an with an agent (or feel free to contact me) to get up to date advice on how to structure these. They are simple and efficient and have significant upside for college funding.",
"title": ""
},
{
"docid": "376847",
"text": "\"Transactions cost is what kills you here. The price of determining who gets what, and then enforcing it. For example; let's say you invested in my electrical engineering class. Then when I get out of school, I go to work. At Starbucks. Where I'm applying literally none of that knowledge or experience--and thus I signed a bad deal. Or what if I change majors? You still have a stake on my lifetime income, but it won't be in the field you helped me into. So college-aged indecision would mean twice as much out of my take-home income for life? Or what if I'd like to buy your percentage back from you? What would be a fair price? Would there be a market to establish it? You should read \"\"The unincorporated man,\"\" which has a system very similar to what you're proposing. In this futuristic story, education and subsistence investment have become astronomically expensive. So in order to send a kid through spaceship-piloting college, you're actually purchasing \"\"shares\"\" of an individual's future earnings like they're a corporation. Parents get 10% when you're born. Government gets 5% in lieu of taxes. These shares have a market value based on income, expenditures, health, etc--pricing individuals just like you'd price a company. In the story, most individuals have sold over 50% of their shares; meaning that they effectively don't have controlling interest over their lives. Their jobs, their homes, all their major decisions are made by the shareholders. So you might take a high-risk job, just because one of your biggest shareholders wants a payday. Of course, since it's on the open market you can buy your shares back. Once you're back over 50%, you're back in control of your life and the majority of your income. The way the author imagines it, it's a pretty comprehensive system. And the book stays delightfully ambiguous as to whether it's debt slavery or a new evolution of liberty. But again; transactions costs. Think of six billion little corporations with all their vital stats and market data. Now imagine voting on the jobs and homes of the potentially hundreds of people in whom you have an interest. It would simply be impossible to keep track of. Honestly, it'd probably be more modest to just pay your student loans.\"",
"title": ""
},
{
"docid": "590276",
"text": "\"Warren Buffett: 'Investing Advice For You--And My Wife' (And Other Quotes Of The Week): What I advise here is essentially identical to certain instructions I’ve laid out in my will. One bequest provides that cash will be delivered to a trustee for my wife’s benefit…My advice to the trustee could not be more simple: Put 10% of the cash in short-term government bonds and 90% in a very low-cost S&P 500 index fund. (I suggest Vanguard’s.) I believe the trust’s long-term results from this policy will be superior to those attained by most investors… Similarly from Will Warren Buffett's investment advice work for you?: Specifically, Buffett wants the trustee of his estate to put 10 percent of his wife's cash inheritance in short-term government bonds and 90 percent in a low-cost S&P index fund - and he tips his hat specifically to Bogle's Vanguard in doing so. Says Buffett: \"\"I believe the trust's long-term results from this policy will be superior to those attained by most investors - whether pension funds, institutions or individuals.\"\"\"",
"title": ""
},
{
"docid": "249089",
"text": "I received an allowance growing up. There were stipulations on what I had to do with it that helped instill the values my parents wanted - in their case they were hoping to teach me to give money to my church, so I had a mandatory amount that I had to give when I received the allowance. To this day I still give money to the church, so I guess it stuck. The allowance was tied to my doing some basic chores around the house - but loosely. It wasn't a reward for doing those chores, but it would be taken away if I didn't do them. Before I was of a legal working age I could do larger unusual tasks around the house for more money. The relationship between chores and some form of allowance is, I think, tricky. I don't think kids should be taught that the only reason to work is to earn money. They won't earn money for keeping their future homes clean or by volunteering at the local food bank, but these are both good things to do. At the same time it is good to teach that work has a reward and that lack of work means lack of a reward. My parents set up a savings account for me quite early. Largely what went in there was birthday cash from relatives (a great thing to talk to any family members who might give your kids gifts about) and the income from my once-yearly sale of baked goods at a craft fair. These were bigger amounts of money that I could take pride in depositing, and keeping them in a bank helped prevent me from spending them willy-nilly. I also got a credit card at the age of 16 (only allowed in some states in the US, not sure about internationally). My parents oversaw my spending habits with it and made sure I always paid in full and on time. The money I spent was tied to my summer work in high school and college. I thought it was extremely valuable to learn how to manage a credit card before college when the card companies often seem to prey on young customers.",
"title": ""
},
{
"docid": "418057",
"text": "\"When considering such a major life decision, with such high potential costs and high potential rewards, I encourage you to consider multiple different potential options. Even if loans were available, they might not be the best option. Less debt and an engineering degree is better than more debt and an engineering degree, both of which are likely better than your current debt and no engineering degree. I encourage you to consider: revisit your aid (which is not just loans), cut expenses, consider alternative aid sources, use your engineering student status to get a better paying job (including more profitable summer employment), check for methods to cut down the cost of your degree, and double-check your plans to make sure you have a long-term plan that makes sense. The first issue, raised in the comments, is whether or not you are getting appropriate financial aid. This does not just mean loans, it includes grants and other forms of assistance. You should be getting in-state tuition, and by searching the tuition of UNC I believe you are. But for future readers, you should make sure you are getting in-state rates, and it not there are options to return to a state where you would get in-state tuition rates, or look into the possibility of pausing your study for one year until you meet in-state funding requirements. You should also ensure your FAFSA information is correct, including your income, family situation (whether or not you are an independent study, as it sounds like you probably are), etc. This effects how many grants you get, and if you are independent this changes maximum federal loan amounts (see website for details). While you don't say what your pay is, the fact that you are working two jobs and having trouble making ends-meet suggests either that you have a spending issue, or that your jobs pay sucks, and possibly both. I've been in both situations, and there are methods for dealing with both. If your spending is not very carefully controlled, that's a big issue. I won't try to rehash all the personal finance advice about this, but I will just warn that when you are desperate and you know there isn't enough money even if you spend perfectly, there is a strong tendency to just give up and not even try because what's the point? Learned helplessness is hell, but it can be overcome with effort and tightly holding on to any glimmer of hope you find to do better each day. If you are in a field like engineering or computing (and some other fields, though I am less personally familiar with the current employment climate in those), there are usually companies who want to hire you as a paid intern or part-time employee in the hopes of getting you when you graduate. Those last two semesters of undergrad are a technicality to employers, they know it doesn't really change your skill set much. Many companies are actually more interesting in hiring someone on who hasn't finished the degree yet than getting someone recently post-degree, because they can get you cheaper and learn if this is a good match before they have to take the big risk of full-time hiring. You need to use this system to your advantage. Its hard when you feel destitute, but talk with career councilors in your school, your department advisor, and/or main administrative staff in your main academic department. Make sure you are on the right mailing lists to see the job offers (many schools require you to subscribe to one because at a school like UNC it easily gets way too much traffic each day). You need field-relevant experience, not just to finish the degree, but to be able to really open up your job opportunities and earning potential. Do not be shy about directly calling/emailing a contact who reaches out to your school looking for \"\"recent graduates\"\", and especially any mention of flexibility on early start for those who are almost finished. You can say you are in your final year (you are), and even ask if they are open to working around a light school schedule while you finish up. Most can end up to be \"\"no\"\", but it doesn't matter - the recruiting contacts want to hire people, so just reaching out early means you can follow up later once you get your degree and finances sorted out and you will have an even easier time getting that opportunity. In technology and engineering, the importance of summer internships cannot be understated, especially as you are now technically at the end of your degree. In engineering and tech fields, internships pay - often very well. Don't worry about it being the job of your dreams. Depending on your set of skills, apply to insurance companies, IT departments in hospitals and banks (even if you thought your coding skills in engineering were minimal), and of course any paying position that might be more directly in your field of interest. Consider ones outside your immediate area or even the more national internships from the bigger name companies, where possible. It is not at all uncommon for tech and engineering internships for undergraduate students to pay $15-$25+ per hour, even where most non-degree jobs might only pay $8 (and I've seen as high as $40 per hour+ in the high cost of living markets, depending on your skill set). I know many people who were paid more as a student intern than they were previously paid as a full-time professional employee. Many schools - including UNC - charge different tuition for distance learning and satellite campuses, and often also offer University-approved online classes. While this is not always a possibility for every student, you should consider the options. It could be that one of the final classes you need towards your degree can be taken at one of these other options, with reduced tuition. This is not always possible with all courses, but is certainly true if you have any of those general education requirements to knock out. Also consider if any of those final requirements have test-out options, such as CLEP test alternatives. Again, not always available, but sometimes you can get class credit for a general education class for Finally, make sure you aren't paying unnecessarily for text books, once you do get the money for tuition. You can sometimes get hand-me-down copies, rent ebooks or physical books from online companies, creative searches for PDF copies, get your book from off-campus local stores, etc. It isn't tuition, but money is money. Attend Part-Time While Working Look into the option of being a half-time student, which is usually 6-8 credit hours, if you can't afford full-time tuition. There is generally a greatly reduced rate, you still qualify for aid programs, and you are still working towards the degree - so you still get access to student resources like internships and job listings that may not be publicly posted. Inquire About Scholarships and School Emergency Assistance While this varies hugely by institution, make sure you check into scholarships you can apply to (even if they are just a few hundred bucks, it helps a lot) in your school (I don't believe the big online searches help, ask the school - but YMMV). Also inquire about any sort of possible help the school provides to students who've had life emergencies, such as your medical issues. Many have programs that are not advertised, designed to help students finish their degree and recover from personal hard times. It's worth the inquiry if you are willing to ask. Any little bit of assistance can help. Don't be afraid to talk with an institution's mental health councilors either, who can help you deal with the psychological difficulty of your situation as well as often being able to connect you to other potential support resources. The pressure can take its tole, and you'll have better long-term opportunities if you build up your support network and options. Student Loan Forbearance While In School If you are trying to save up every last dollar for tuition to finish the degree, but you have to pay loans now, call up the provider to ask about temporary delays on your student loan payments. Many have time-limited hardship allowances, and between the medical bills, low income, and returning to school, they may be willing to give you a few months break until you get back to school and the in-school provisions kick in. Skip a Semester If Necessary To Save Money If you can only raise enough for one semester, then need to skip a semester to build up more funds, that happens, it's OK. Be strategic, and check on loan forbearance. Usually being out for one semester is allowed by student loan companies before you owe them payment, and if you re-enroll you don't have to start making payments yet. Double-check on Credit Expiration and Degree Requirements Make sure you talk to someone who knows what they are talking about, especially in terms of credit expiration. Policies vary, and sometimes an advisor is able to put in a special request to waive you through some of these issues. Academia is heavily, heavily reliant on developing a good relationship and clear communication with an advisor who is willing to work with you to achieve your goals. Written policies are sometimes very firm, and sometimes all you have to do is ask the right person and poof, suddenly the rules change. It's a weird system, but don't be afraid to explain your situation and ask what can be done. Don't assume a written policy is 100% ironclad - sometimes it is, but it often isn't. Inquire About Other Government and Community-based Assistance Being destitute is awful, and having to ask for help can feel terrible in it's own way, but doing what you have to do to have a better future can mean pushing through and being willing to ask for help. This can mean asking parents and close family if they can contribute to help you finish your degree, but this also means checking with your local community programs to see if you qualify for anything. Many communities have food pantries and related programs that will help you even if you don't qualify for something like SNAP (aka food stamps), because they know times can get hard for anyone and they want you to spend what little money you have on building a better life. Your university may even run a food pantry for students in need - use it. Get what assistance you can, minimize spending in any way you can manage, put all the money towards doing what you need to do to get to a better place. It's even nicely reciprocal - once you work through your hard times and get things on track, you can return the favor and help give back to programs like the ones that helped you. Make Sure Your Long-Term Goal Makes Sense Finally, this is all predicated on pulling out all the stops to finish your degree. But this assumes that this is a good plan. Not all degrees are helpful for all people in all areas of the country. Do your own research to make sure you aren't throwing good money after bad, and are pursuing a goal that will make sense for you and what you want. The cost of a degree keeps going up, but it remains true that many sets of skills and degree-holding candidates are in demand and can command high salaries that blow away the cost of college in comparison. If you actually have a good chance of going from struggling to make $8/hour to making $50k-90k a year, based on your developed skills, experience, and professional network, then reasonable student loan debt is a worthy investment. If, on the other hand, you wrack up tens of thousands of more dollars in debt just to say you did and still have to work the same kinds of jobs, that's not really much of an investment at all. Good luck on your journey, and best wishes towards better days - regardless of what path you choose. Finally, make sure you aren't paying unnecessarily for text books, once you do get the money for tuition. You can sometimes get hand-me-down copies, rent ebooks or physical books from online companies, creative searches for PDF copies, get your book from off-campus local stores, etc. It isn't tuition, but money is money. Look into the option of being a half-time student, which is usually 6-8 credit hours, if you can't afford full-time tuition. There is generally a greatly reduced rate, you still qualify for aid programs, and you are still working towards the degree - so you still get access to student resources like internships and job listings that may not be publicly posted. While this varies hugely by institution, make sure you check into scholarships you can apply to (even if they are just a few hundred bucks, it helps a lot) in your school (I don't believe the big online searches help, ask the school - but YMMV). Also inquire about any sort of possible help the school provides to students who've had life emergencies, such as your medical issues. Many have programs that are not advertised, designed to help students finish their degree and recover from personal hard times. It's worth the inquiry if you are willing to ask. Any little bit of assistance can help. Don't be afraid to talk with an institution's mental health councilors either, who can help you deal with the psychological difficulty of your situation as well as often being able to connect you to other potential support resources. The pressure can take its tole, and you'll have better long-term opportunities if you build up your support network and options. If you are trying to save up every last dollar for tuition to finish the degree, but you have to pay loans now, call up the provider to ask about temporary delays on your student loan payments. Many have time-limited hardship allowances, and between the medical bills, low income, and returning to school, they may be willing to give you a few months break until you get back to school and the in-school provisions kick in. If you can only raise enough for one semester, then need to skip a semester to build up more funds, that happens, it's OK. Be strategic, and check on loan forbearance. Usually being out for one semester is allowed by student loan companies before you owe them payment, and if you re-enroll you don't have to start making payments yet. Make sure you talk to someone who knows what they are talking about, especially in terms of credit expiration. Policies vary, and sometimes an advisor is able to put in a special request to waive you through some of these issues. Academia is heavily, heavily reliant on developing a good relationship and clear communication with an advisor who is willing to work with you to achieve your goals. Written policies are sometimes very firm, and sometimes all you have to do is ask the right person and poof, suddenly the rules change. It's a weird system, but don't be afraid to explain your situation and ask what can be done. Don't assume a written policy is 100% ironclad - sometimes it is, but it often isn't. Being destitute is awful, and having to ask for help can feel terrible in it's own way, but doing what you have to do to have a better future can mean pushing through and being willing to ask for help. This can mean asking parents and close family if they can contribute to help you finish your degree, but this also means checking with your local community programs to see if you qualify for anything. Many communities have food pantries and related programs that will help you even if you don't qualify for something like SNAP (aka food stamps), because they know times can get hard for anyone and they want you to spend what little money you have on building a better life. Your university may even run a food pantry for students in need - use it. Get what assistance you can, minimize spending in any way you can manage, put all the money towards doing what you need to do to get to a better place. It's even nicely reciprocal - once you work through your hard times and get things on track, you can return the favor and help give back to programs like the ones that helped you. Finally, this is all predicated on pulling out all the stops to finish your degree. But this assumes that this is a good plan. Not all degrees are helpful for all people in all areas of the country. Do your own research to make sure you aren't throwing good money after bad, and are pursuing a goal that will make sense for you and what you want. The cost of a degree keeps going up, but it remains true that many sets of skills and degree-holding candidates are in demand and can command high salaries that blow away the cost of college in comparison. If you actually have a good chance of going from struggling to make $8/hour to making $50k-90k a year, based on your developed skills, experience, and professional network, then reasonable student loan debt is a worthy investment. If, on the other hand, you wrack up tens of thousands of more dollars in debt just to say you did and still have to work the same kinds of jobs, that's not really much of an investment at all. Good luck on your journey, and best wishes towards better days - regardless of what path you choose.\"",
"title": ""
},
{
"docid": "186102",
"text": ">I propose to make the requirements for finish high school and college degrees much much higher, as it was in the past. Not gonna happen. The paradigm is that low scores are entrenched and therefore unable to be lifted without the kids parents having higher education. Therefore, waiting for disadvantaged kids to get higher scores will not happen until they get accepted into college. If you force schools to gain their income from future students earnings they will have high concern for kids that have a good P/E ratio. It will also stop the loan industry from putting these kids into debt. The downside is that it may turn colleges into trade techs, but that is much better than what is going on now: useless degrees and high debt.",
"title": ""
},
{
"docid": "174818",
"text": "\"> The fact that there is way more educated people than is even remotely necessary. Yes, you got it! I agree with you and this is the bottom of line of the whole story. Once, to finish high school was not an easy accomplishment. To be accepted to college was an accomplishment, to survive the first year was an accomplishment, and not to mention to graduate with a bachelor degree. The few who managed to accomplished that were accomplished men and women who got full benefits of their accomplishments, guaranteed!!!! Today, also as a former adjunct professor in college, I can tell you you that anyone graduates from high school (\"\"no student left behind\"\"), everyone(!), many barely know how to read, write or even tackle a simple logical question. And same in college: I was told I can't fail my students except in extreme cases. So what do we have here? You said it correct and clearly: >Everybody having a college degree drives the value down for everybody...which is exactly what is happening. Further! It's just an industry to make money, put people into debt, give them almost worthless pieces of papers, force them to also study for a master's degree and reduce the pay for qualified people with degrees. Even Harvard! You would think that for $80,000/year tuition, you get good education. Instead, you are put in a auditorium with 500 other students for lectures. > Things need to be turned on their head. Yes! You got it here too! > I propose that Colleges need to receive their income as a percentage of the first 10-15 years of income from their students. Disagree! I propose to make the requirements for finish high school and college degrees much much higher, as it was in the past. As you said, too many people have [worthless] degrees!!!! The few who get degree, are accomplished people and will reap the benefits, including their employers. This is also the best formula for people to come out of poverty and low social-economic family background. Right now, if you are smart but from a poor background, oh yes, you get a degree, but it's worthless and won't help you much. But if the requirements are high, and you are smart, you are all set! As for people who fail high school and don't get degrees, they will not be spoiled as today's kids with all their degrees! Someone needs to be a plumber, electrician, trade or a clerk. And these jobs make very good many, much better than bank tellers with a bachelor degree. Finally, there's no way someone who graduate high school today, even a relatively good student, that they could survive high school of the 50s and 60s. They will fail miserably, also for bad attitudes, discipline, and capacity to handle simple requirements.\"",
"title": ""
},
{
"docid": "312752",
"text": "> I'm not so sure that performance measurement of students is all that difficult You assume that student performance is a good proxy for teacher performance. One of the bigger influences on student performance is parent engagement (particularly the parent engagement that happens prior to school age, but also the engagement once they're in school). Often these differences run along socioeconomic lines, and schools are generally divided on neighborhood lines with students attending the school closest to their home. If you judge based on student performance, you'll likely assume that the teachers in the richer neighborhoods are better (students perform better on standardized tests, students are more likely to graduate high school and even go on to college, etc). The fact is, there's a lot of good teachers who take the hard jobs because even a little improvement can go a long way. Put those same teachers in the richer neighborhoods and you might judge things differently.",
"title": ""
},
{
"docid": "335429",
"text": "\"First, it's clear from your story that you very likely should be able to receive some financial aid. That may be in the form of loans or, better, grants in which you just get free money to attend college. For example, a Pell grant. You won't get all you'd need for a free ride this way, but you can really make a dent in what you'd pay. The college may likely also provide financial aid to you. In order to get any of this, though, you have to fill out a FAFSA. There are deadlines for this for each state and each college (there you would ask individually). I'd get looking into that as soon as you can. Do student loans have to be paid monthly? Any loan is a specific agreement between a lender and a borrower, so any payment terms could apply, such as bimonthly or quarterly. But monthly seems like the most reasonable assumption. Generally, you should assume the least favorable (reasonably likely) terms for you, so that you are prepared for a worst-case scenario. Let's say monthly. Can I just, as I had hoped, borrow large sums of money and only start paying them after college? Yes. That is a fair summary of all a student loan is. Importantly, though, some loans are federal government subsidized loans for which the interest on the loan is paid for you as long as you stay in college + 6 months (although do check that is the current situation). Unsubsidized loans may accrue interest from the start of the loan period. If you have the option, obviously try hard to get the subsidized loans as the interest can be significant. I made a point to only take subsidized loans. WARNING: Student loans currently enjoy a (nearly?) unique status in America as being one of the only loan types that are not forgivable in bankruptcy. This means that if you leave college with $100,000 in debt that begins accruing interest, there is no way for you to get out of it short of fleeing the country or existence. And at that point the creditors may come after your mother for the balance. These loans can balloon into outrageous amounts due to compounding interest. Please have a healthy fear of student loans. For more on this, listen to this hour long radio program about this. Would a minimum wage job help, Of course it will \"\"help\"\" but will it \"\"help enough\"\"? That depends on how much you work. If you make $7.50/hr and work 20 hrs/week for all but 3 weeks of the year, after taxes you will be adding about $6,000 to offset your costs. In 3 years of college (*see below), that's $18,000, which, depending on where you go, is not bad at helping defray costs. If you are at full-time (40 hrs), then it is $12k/yr or $36k toward defraying costs. These numbers are nothing to sniff at. Do you have any computer/web/graphics skills? It's possible you could find ways to make more than minimum wage if you learn some niche IT industry skill. (If I could go back and re-do those years I wouldn't have wasted much time delivering pizzas and would have learned HTML in the 90s and would have potentially made some significant money.) would college and full-time job be manageable together? That's highly specific to each situation (which job? how far a commute to it? which major? how efficient are you? how easily do you learn?) but I would say that, for the most part, it's not a good idea, not only for the academic-achievement side of it, but the personal-enrichment aspect of college. Clubs, sports, relationships, activities, dorm bull sessions, all that good stuff, they deserve their space and time and it'd be a shame to miss out on that because you're on the 2nd shift at Wal-Mart 40hrs/week. How do I find out what scholarships, grants, and financial aid I can apply for? Are you in a high school with a career or guidance counselor? If so, go to that person about this as a start. If not, there are tons of resources out there. Public libraries should have huge directories of scholarships. The Federal Student Loan program has a website. There are also a lot of resources online found by just searching Google for scholarships--though do be careful about any online sources (including this advice!). Sermon: Lastly, please carefully consider the overall cost vs. benefit to you. College in 2012 is anything but cheap. A typical price for a textbook is $150 or more. Tuition and board can range over $40k at private colleges. There is a recent growing call for Americans to re-think the automatic nature of going to college considering the enormous financial burden it puts many families under. Charles Murray, for one, has put out a book suggesting that far too many students go to college now, to society's and many individuals' detriment (he's a controversial thinker, but I think some of his points are valid and actually urgent). With all that said, consider ways to go to college but keep costs down. Public colleges in your state will almost always be significantly cheaper than private or out-of-state. Once there, aim for As and Bs--don't cheat yourself out of what you pay for. And lastly, consider a plan in which you complete college in three years, by attending summer courses. This website has a number of other options for helping to reduce the cost of college.\"",
"title": ""
},
{
"docid": "48071",
"text": "I would say you are wrong. I think you're underestimating a good warehouse worker. There is a skill set involved, and many do not have it. Sadly, many people don't know any better than to arrive high, drunk, hung over, late, or not at all on a regular, for starters. Most warehouse workers don't just lift heavy things anymore. In fact, probably the majority never lift anything heavy at all. They run power equipment. Big, expensive, dangerous power equipment that does most of the lifting. Again, not everyone can handle that. One power equipment accident can end up costing the company tens of thousands of dollars. Aside from that, the people performing those jobs are hardly the only employees present. Someone has to check in the trucks, audit the receivers, distribute the work of sorting, coreograph the loading and distribution of product out to the stores, maintain the computer systems, and a thousand other small tasks on a daily basis. I can assure you these positions require a whole lot more skills than the average loom worker in the 1800s was required. Really, I find it scary how much you are devaluing these people. The fact most well-paying warehouses constantly go a few hands short is testiment to the fact good people are not actually a dime a dozen. Edit a word. Ninja Edit: Another thing about this is that you seem to want to believe people had a choice in not developing whatever killer skillset it is you think makes you better than them. The reality is many very intelligent people cannot afford college. They don't have parents willing to give them a dime or a leg up, or their parents simply do not have the dime or the leg up to give them even if they wanted to. They're smart, but had to work during high school to support a portion of their own expenses, and that hurt their grades a bit. Or they were young, idiotic, and had little guidance because their parents were constantly away working their arses off for a pitance to survive on, so they goofed off in high school more than they ought resulting in an inability to qualify for scholarships. Suddenly, they're grown. They have to provide housing, food, and whatever for themselves, so they get crap jobs thinking they'll find a way to parlay that into skills or education when the reality is most employers just want to suck as much out of the employee for the least possible contribution. Any general manager of a large facility will tell you bragging rights on the golf course are to he who spends the least for the most work done. The majority of low skill low pay workers would gladly go back to college if only they could. Even if they can somehow scrape together the cash required - now over $8k a year for tuition, a crappy dorm and a food ticket at state colleges in my state, and books will run you $500 a semester for many majors - there is the issue of time. After working a grueling hopefully full-time job, they'd need to find it in them to stay awake during class and to complete assignments. On top of that, there is the question of timing. Especially in low skill jobs, it is usually required that the employee be available at company pleasure. Try finding a school in your area which has the classes you need times you can attend. Good luck with that. But wait! There are government subsidies! Yeah, good luck with that as well. If you've been working any half-decent job and apply, and are under 25 and your parents also make half-decent wages, you will be lucky to be offered loans. They aren't even low interest loans anymore. Also, god forbid your parents have a little emergency nest egg saved up from years of hard labor in the salt mines. Or - horrors - own a small, crappy, cookie-cutter, not-aging-well tract home free and clear. That'll cost you big in financial assistance from the goverment.",
"title": ""
},
{
"docid": "112233",
"text": "\"First of all, I'm happy that the medical treatments were successful. I can't even imagine what you were going through. However, you are now faced with a not-so-uncommon reality that many households face. Here's some other options you might not have thought of: I would avoid adding more debt if at all possible. I would first focus on the the cost side. With a good income you can also squeeze every last dollar out of your budget to send them to school. I agree with your dislike of parent loans for the same reasons, plus they don't encourage cost savings and there's no asset to \"\"give back\"\" if school doesn't work out (roughly half of all students that start college don't graduate) I would also avoid borrowing more than 80% of your home's value to avoid PMI or higher loan rates. You also say that you can pay off the HELOC in 5 years - why can you do that but not cash flow the college? Also note that a second mortgage may be worse that a HELOC - the fees will be higher, and you still won't be able to borrow more that what the house is worth.\"",
"title": ""
},
{
"docid": "30590",
"text": "\"College is an institution that's modern purpose is obscured and obstructed by outdated ideas about what it used to be. College nowadays is de facto vocational training for white collar professions. But college used to be a place of learning, knowledge, discovery, and inquiry for pure academics, intellectuals, and wealthy scions. People go to college as a prerequisite for a career, but instead encounter a culture of learning for learning's sake, a system originally designed to turn independently wealthy gentlemen into erudite gentlemen. As they are today, the majority of colleges are traps for unwitting, would-be workers. For all the high school graduates that go to college for the hope of a better life, a high percentage are lured and deceived into learning that amounts to the theft of four years and their tuition, including majors like archaeology or history. Whatever the value of such horizon broadening is to society, it is wrong to ask students to pay the bill for irrelevant learning. It is unconscionable that today's employers expect employees to have financed the cost of a small house to be qualified to sit at a desk, answer phone calls, and fill out a spreadsheet for less than $40,000 per year. Meanwhile, colleges cling to their delusional self-image as academic institutions. How many majors actually prepare students to get a career? A handful of majors have obvious specific outcomes, like dentistry or computer science, though even the most basic programming job is more specialized than \"\"CS graduate.\"\" How many people major in front-end web development? What job does Business Administration prepare students for? \"\"Business.\"\" Learn the same thing from a degree called project management and that student goes from unemployed to earning six figures. Academic colleges have their place, but we should have a system that provides credentials and focused, relevant instruction in less than two years with job specific training, marketable skills, and job placement for much, much less money. I propose that colleges be separated out into academic institutions and white collar vocational schools, and that they be given equal prestige, academic rigorousness, and consideration for entry level white collar work.\"",
"title": ""
},
{
"docid": "366865",
"text": "Smart parents not wanting to get stuck with a student loan or co-signing on a loan. because rent is so high Are you able to live with your parents? Is there anyway to reduce the cost of rent like renting a room? Can you move somewhere where the rent is cheaper? working 25 hours per week Working 25 hours per week and taking 6 hours is a pretty light schedule. It is not even 40 hours per week. What is stopping you from working 40 hours and paying for school from your salary? In my own life I created a pretty crappy situation for myself when I was a young man. I really wanted to go to a prestigious university, but ended up going to a community college, and then to a university that was lesser known in a less expensive area. I had to work like crazy, upwards of 50 hours per week. I also took a full load in a difficult degree program. You probably don't have to go to the extremes that I went through, but you can work more. Most adults work at their jobs well more than 40 hours per week, then come home and continue to work (on the house, raising kids, trying to start a side business, etc...). So you might as well become an adult now. There are ways to become independent from your parents for FAFSA like have a baby, get married, or join the military. I'd only recommend the last one as you will also receive the GI Bill. Another option is to try and obtain a job that offers financial aid.",
"title": ""
},
{
"docid": "148346",
"text": "The average of a dozen good answers is close to what would be right, the wisdom of crowds. But any one answer will be skewed by one's own opinions. The question is missing too much detail. I look at $400K as $16K/yr of ongoing withdrawals. How much do you make now? When the kids are all in school full time, can your wife work? $400K seems on the low side to me, especially with 3 kids. How much have you saved for college? The $150K for your wife is also a bit low. Without a long tangent on the monetary value of the stay at home spouse, what will you spent on childcare if she passes? Term life also has a expiration date. When my daughter was born, my wife and I got 20 year term. She is now 16, her college account fully funded, and we are semi-retired. The need for insurance is over. If one of us dies, the survivor doesn't need this big of a house, and will have more than they need to be comfortable in a downsized one. My belief is that the term value should bridge the gap to the kids getting through college and the spouse getting resettled. Too much less, I'd have left my wife at risk. Too much more, she'd be better off if I were dead. (I say that half joking, the insurance company will often limit the size policy to something reasonable.)",
"title": ""
},
{
"docid": "353186",
"text": "Should I use the money to pay off student loans and future grad expenses for me? Yes. The main drawback to student loans is that they cannot be gotten rid of except by paying them off (other than extreme circumstances such as death or complete disability). A mortgage, car loan, or other collateralized loans can be dealt with by selling the underlying collateral. Credit card loans can be discharged in bankruptcy. Stop borrowing for college, pay for it in cash, then decide what to do with the rest. Make sure you have a comfortable amount saved for emergencies in a completely liquid account (not a retirement account or CDs), and continue to pay off with the rest. You might also consider putting some away for your kids' college, so I want to get my older son into a private middle school for 2 years. They have a hardy endowment and may offer us a decent need based scholarship if we look worthy on paper I have a hard time getting behind this plan with a 238K mortgage. If you want to apply for scholarships that's great - but don't finagle your finances to look like you're poor when you have a quarter-million-dollar house. If you want to save some for private school then do that out of what you have. Otherwise either rearrange your priorities so you can afford it or private school might not be in the cards for you. That said- while it was a blessing to be able to pay off the second mortgage and credit cards, your hesitancy to pay off the student loans makes me wonder if you will start living within your means after the loans are paid off. My concern is that your current spending levels that got you in this much debt in the first place will put you back in debt in the near future, and you won't have another inheritance to help pull you out. I know that wasn't your question, but I felt like I needed to add that to my answer as well.",
"title": ""
},
{
"docid": "518266",
"text": "FASFA financial aid formulas determine 'expected family contribution'. For example my alma mater now has a 'list price of over $65k/year. The average student today actually pays $42k/year after grants. Students with rich parents pay more than that. Students with poor parents pay less than that. Lets say list prices for my kids colleges average $110k/year while they are in school. If we 'only' make $200k then based on our income alone, EFC would start in the low $50ks per year. If we have $1M saved in taxable accounts, 529s, rental properties, etc, then we also have to pay 5.64% of the value of those every year for the eight years my kids will be attending - an *extra* $56.4k/year every year for 8 years. If that $1M is in assets that don't count such as retirement accounts and equity in primary residence, then it doesn't increase the price my kids are billed. That's a pretty big incentive to put everything I can in home equity, Roth IRA, Spousal Roth IRA, traditional 401k, after-tax 401k, and HSA. If I could afford to save more I'd switch from traditional to Roth 401k and pre-pay retirement taxes at a higher marginal rate rather than have the savings on the side subjected to the college wealth/income taxes which are effectively a much higher difference between the 25% (now) and 15% (later) federal tax brackets. Profile and consensus formulas have slightly different percentages and count some home equity if you have an expensive house, but the general idea is the same.",
"title": ""
},
{
"docid": "70668",
"text": "\"I will answer the question from the back: who can NOT afford luxury cars? Those whose parents paid for their college education, cannot afford luxury cars, but buy them anyway. Why? I have what may seem a rather shocking proposition related to the point of not saving for kids' college: parents do NOT owe children a college education. Why should they? Did your parents fund your college? Or did you get it through a mix of Pell grants, loans, and work? If they did, then you owe them $ back for it, adjusted for inflation. If they did not, well then why do you feel your children deserve more than you deserved when you were a child? You do not owe your children a college education. They owe it to themselves. Gifts do not set one up for success, they set one up for dependence. I will add one more hypothesis: financial discipline is best learned through one's own experiences. When an 18+ year old adult gets a very large amount of money as a gift every year for several years (in the form of paid tuition), does that teach them frugality and responsibility? My proposition is that those who get a free ride on their parents' backs are not well served in terms of becoming disciplined budgeters. They become the subjects of the question in this post: those why buy cars and houses they cannot afford, and pay for vacations with credit cards. We reap what we sow as a society. Of course, college is only one case in point, but a very illustrative one. The bigger point is that financial discipline can only be developed when there are opportunities to develop it. Such opportunities arise under one important condition: financial independence. What does buying children cars for their high-school graduation, buying them 4 years of college tuition, and buying them who knows what else (study abroad trips, airfare, apartment leases, textbooks, etc. etc.) teach? Does it teach independence or dependence? It can certainly (at least that's what you hope for) teach them to appreciate when others do super nice things for them. But does free money instill financial responsibility? Try to ask kids whose parents paid for their college WHY they did it. \"\"Because my parents want me to succeed\"\" is probably the best you can hope for. Now ask them, But do your parents OWE you a college education? \"\"Why yes, I guess they do.\"\" Why? \"\"Well, I guess because they told me they do. They said they owe it to me to set me up for success in life.\"\" Now think about this: Do people who become financially successful achieve that success because someone owed something to them? Or because they recognized that nobody owes them anything, and took it upon themselves to create that success for themselves? These are not very comfortable topics to consider, especially for those of you who have either already sunk many tens of thousands of dollars into your childrens' college education. Or for those who have been living very frugally and mindfully for the past 10-15 years driven by the goal of doing so. But I want to open this can of worms because I believe fundamentally it may be creating more problems than it is solving. I am sure there are some historical and cultural explanations for the ASSUMPTION that has at some point formed in the American society that parents owe their children a college education. But as with most social conventions, it is merely an idea -- a shared belief. It has become so ingrained in conversations at work parties and family reunions that it seems that many of those who are ardent advocates of the idea of paying for their childrens' education no longer even understand why they feel that way. They simply go with the flow of social expectations, unwilling or unable to question either the premises behind these expectations, or the long-term consequences and results of such expectations. With this comment I want to point to the connection between the free financial gifts that parents give to their (adult!) children, and the level of financial discipline of these young adults, their spending habits, sense of entitlement, and sense of responsibility over their financial decisions. The statistics of the U.S. savings rate, average credit card debt, foreclosures, and bankruptcy indeed tell a troubling story. My point is that these trends don't just happen because of lots of TV advertising and the proverbial Jones's. These trends happen because of a lack of financial education, discipline, and experience with balancing one's own checkbook. Perhaps we need to think more deeply about the consequences of our socially motivated decisions as parents, and what is really in our children's best interests -- not while they are in college, but while they live the rest of their lives after college. Finally, to all the 18+ y.o. adult 'children' who are reeling from the traumatic experience of not having their parents pay for their college (while some of their friends parents TOTALLY did!), I have this perspective to offer: Like you are now, your parents are adults. Their money is theirs to spend, because it was theirs to earn. You are under no obligation to pay for your parents' retirement (not that you were going to). Similarly your parents have no obligation to pay for your college. They can spend their money on absolutely whatever they want: be it a likeside cottage, vacations, a Corvette, or slots in the casino. How they spend their money is their concern only, and has nothing to do with your adult needs (such as college education). If your parents mismanage their finances and go bankrupt, it is their obligation to get themselves back in the black -- not yours. If you have the means and may be so inclined, you may help them; if you do not or are not, fair enough. Regardless of what you do, they will still love you as their child no less. Similarly, if your parents have the means and are so inclined, they may help you; if they do not or are not, fair enough. Regardless of what they do, you are to love them as your parents no less. Your task as an adult is to focus on how you will meet your own financial needs, not to dwell on which of your needs were not met by people whose finances should well be completely separate from yours at this point in life. For an adult, to harbor an expectation of receiving something of value for free is misguided: it betrays unjustified, illusory entitlement. It is the expectation of someone who is clueless as to the value of money measured by the effort and time needed to earn it. When adults want to acquire stuff or services, they have to pay for these things with their own money. That's how adults live. When adults want to get a massage or take a ride in a cab, are they traumatized by their parents' unfulfilled obligation to pay for these services? No -- they realize that it's their own responsibility to take care of these needs. They either need to earn the money to pay for these things, or buy them on credit and pay off the debt later. Education is a type of service, just like a massage or a cab ride. It is a service that you decide you need to get, in order to do xyz (become smarter, get a better paying job, join a profession, etc.). Therefore as with any other service, the primary responsibility for paying for this service is yours. You have 3 options (or their combination): work now so that you can earn the money to pay for this service later; work part-time while you are receiving this service; acquire the service on credit and work later to pay it off. That's it. This is called the real world. The better you can deal with it, the more successful you will become in it. Good luck!\"",
"title": ""
},
{
"docid": "375496",
"text": "\"This is the best tl;dr I could make, [original](https://www.vox.com/policy-and-politics/2017/2/28/14359140/chetty-friedman-college-mobility) reduced by 95%. (I'm a bot) ***** > There are the highly effective schools that barely enroll any poor kids but do tons for the few they do have, and the highly ineffective schools that enroll a lot of poor kids but offer them little. > That&#039;s part of what makes this research so exciting: It lets us distinguish between high-performing and low-performing schools, but it also creates an agenda for follow-up research seeking to identify what makes, say, the Technical Career Institutes in New York so much more effective than Moultrie Technical College at making poor students substantially better off. > The authors examined schools where the share of poor kids enrolled rose over time, and checked to see if they became less successful at elevating those kids economically. ***** [**Extended Summary**](http://np.reddit.com/r/autotldr/comments/6yzw3z/these_colleges_are_better_than_harvard_at_making/) | [FAQ](http://np.reddit.com/r/autotldr/comments/31b9fm/faq_autotldr_bot/ \"\"Version 1.65, ~206881 tl;drs so far.\"\") | [Feedback](http://np.reddit.com/message/compose?to=%23autotldr \"\"PM's and comments are monitored, constructive feedback is welcome.\"\") | *Top* *keywords*: **school**^#1 **student**^#2 **percent**^#3 **top**^#4 **poor**^#5\"",
"title": ""
},
{
"docid": "598356",
"text": "\"It depends. \"\"High net worth individuals\"\" is very subjective. Lets say a person is worth 1.5 million. High, but not super high. For one, they should have an umbrella policy. Until your net worth is above 300K, you really don't need an umbrella policy. They should insure their home and cars, but should probably have high deductibles. Health insurance is a must as a bad illness can wipe them out. They should have long term care insurance when they reach age 60. Now lets say a person is worth about 10 million. They might be able to self insure basic transportation and probably don't need long term care insurance. However, they may choose to carry the full coverage car insurance, or other lines, because it is a value. In conclusion insurance needs change based on a person's net worth and income. It is very hard to make a blanket statement without details of the makeup of one's net worth and how they earn their income. Having said all of that, a high net worth (HNW) individual may never be able to drop certain coverage. Lets say that a HNW owns a 50K condo, 1K square foot condo. Given that the outside structure is covered by the HOA the insurance on such a unit only covers the contents and liability. The contents could easily be floated by the HNW individual, but not the liability. It is probably a requirement, on their umbrella policy, that they carry the maximum liability protection on their vehicles and properties. In the case above they would carry a policy for the purposes of liability protection. This could also be true of their dependents. Say for example, their adult child receives some financial assistance from their parents (like college being paid for). The HNW individuals should have their child cover the maximum liability on the auto policy. According to this site: A person with a net worth of 1.5 million would be in the 90-95 percentile, a person with 10 million in the 99th. This article does a decent job of describing what constitutes a HNW person or household. Namely 1 million in investable assets, which is of course a bit different then net worth.\"",
"title": ""
},
{
"docid": "155640",
"text": "\"John's answer is similar to what I was thinking. You should invest in insurance \"\"because there's an insurance salesman who needs to pay to send his kid to college.\"\" I will never be a fan of any type of permanent insurance, and I think it wrong to sell a single person with no dependents such a policy. I've used the expression \"\"Variable Annuities are sold, not bought.\"\" I feel the same about these insurance policies. The best advice I can offer in a short reply is this: If you need life insurance, buy term. Save as much as you can, 10% minimum, more if you are able. A young person should be saving for retirement and to position them self to buy their first house, if that's what they wish. What good is a full up Whole Life policy when you need to raise $40K to put down on a house? Sorry to sound like I'm lecturing, this is one of my hot points.\"",
"title": ""
},
{
"docid": "87379",
"text": "\"@farnsy has provided a good answer. I'm only addressing my comment about the data quality. The portfolio optimization technique you employed is very sensitive to the inputs. In particular, it relies entirely on the mean and (co)variance assumptions (i.e. the first two moments) and the results could change drastically with very small amount of change in the inputs. To see that, you can make up some inputs for the solver you have, and try adjusting the inputs a little bit and see the results. Therefore if you decide to take this approach, data quality is very crucial. EDIT: What I meant by \"\"data quality\"\" I have no experience with this website but this should be easy to spot check. The answer is usually \"\"yes\"\" for liquid assets. Illiquid assets can often be priced at a level with no volume, and the bid-ask spread could be huge. Should I close my eyes on the fact that these cryptocurencies aren't perfectly priced in my currency and use another one (such as the dollar) You seem to have concern about data quality in at least the price quoted in your currency and are thinking about using data quoted in USD, but would it be any better? The law of one price tells us that there shouldn't be any discrepancy between prices in different currencies (otherwise there would be arbitrage). In addition, (when compared to traditional assets) cryptocurrency price data has a shorter data history, and with lower liquidity in the market. The short history means you have less data to infer the characteristics of the price behavior. Low liquidity means the volatility may well be underestimated. So we have an input-sensitive technique combined with not-so-perfect data. I wouldn't allocate my money solely based on the result of this exercise. EDIT: I have quite some reservation about doing portfolio optimization for cryptocurrency. Personally I'm not a fan of the technique as is. The optimization has an underlying assumption that returns follow a certain distribution, and correlation is fixed. I don't know if you can make such assumption for cryptocurrencies. From what I read about BTC for example, it seems to have a high risk exposure concerning Chinese monetary policy. For that kind of assets perhaps a fundamental analysis approach is a better one. Also if you would like to learn more about portfolio optimization, try quant.SE\"",
"title": ""
}
] |
5093
|
What forms (S-1, 8-K, etc) and keywords in news headlines signify dilution?
|
[
{
"docid": "457532",
"text": "Possibles: stock offering, secondary placement, increase authorized number of shares, shelf registration.",
"title": ""
}
] |
[
{
"docid": "125140",
"text": "\"If you elect to have the company treated as an S corp, the profits/losses of the company will pass through to the shareholders (i.e. you) on a Schedule K-1 form every year. These amounts on the Schedule K-1 are taxable whether or not the company actually distributed the money to you. Typically, the company will distribute profits to the shareholders because they will have to pay taxes on this amount. https://turbotax.intuit.com/tax-tools/tax-tips/Small-Business-Taxes/What-is-a-Schedule-K-1-Tax-Form-/INF19204.html So the money held in the company's bank accounts won't appear on your taxes per se, but the profits/losses as reported on the company's tax return will pass through to you on the Schedule K-1. Typically these amounts are taxed as income. Your tax accountant can advise you on how much money you can/should take through regular payroll and how much can be distributed as a shareholder, as well as help you prepare the corporate tax returns and schedule(s) K-1 every year. There are tax advantages to taking money out of the company through distributions instead of payroll, but the amounts can be scrutinized and subject to a criterion of \"\"reasonable compensation\"\", hence my recommendation for a tax accountant.\"",
"title": ""
},
{
"docid": "214358",
"text": "Here is a quote from the IRS website on this topic: You may be able to deduct premiums paid for medical and dental insurance and qualified long-term care insurance for yourself, your spouse, and your dependents. The insurance can also cover your child who was under age 27 at the end of 2011, even if the child was not your dependent. A child includes your son, daughter, stepchild, adopted child, or foster child. A foster child is any child placed with you by an authorized placement agency or by judgment, decree, or other order of any court of competent jurisdiction. One of the following statements must be true. You were self-employed and had a net profit for the year reported on Schedule C (Form 1040), Profit or Loss From Business; Schedule C-EZ (Form 1040), Net Profit From Business; or Schedule F (Form 1040), Profit or Loss From Farming. You were a partner with net earnings from self-employment for the year reported on Schedule K-1 (Form 1065), Partner's Share of Income, Deductions, Credits, etc., box 14, code A. You used one of the optional methods to figure your net earnings from self-employment on Schedule SE. You received wages in 2011 from an S corporation in which you were a more-than-2% shareholder. Health insurance premiums paid or reimbursed by the S corporation are shown as wages on Form W-2, Wage and Tax Statement. The insurance plan must be established, or considered to be established as discussed in the following bullets, under your business. For self-employed individuals filing a Schedule C, C-EZ, or F, a policy can be either in the name of the business or in the name of the individual. For partners, a policy can be either in the name of the partnership or in the name of the partner. You can either pay the premiums yourself or your partnership can pay them and report the premium amounts on Schedule K-1 (Form 1065) as guaranteed payments to be included in your gross income. However, if the policy is in your name and you pay the premiums yourself, the partnership must reimburse you and report the premium amounts on Schedule K-1 (Form 1065) as guaranteed payments to be included in your gross income. Otherwise, the insurance plan will not be considered to be established under your business. For more-than-2% shareholders, a policy can be either in the name of the S corporation or in the name of the shareholder. You can either pay the premiums yourself or your S corporation can pay them and report the premium amounts on Form W-2 as wages to be included in your gross income. However, if the policy is in your name and you pay the premiums yourself, the S corporation must reimburse you and report the premium amounts on Form W-2 as wages to be included in your gross income. Otherwise, the insurance plan will not be considered to be established under your business. Medicare premiums you voluntarily pay to obtain insurance in your name that is similar to qualifying private health insurance can be used to figure the deduction. If you previously filed returns without using Medicare premiums to figure the deduction, you can file timely amended returns to refigure the deduction. For more information, see Form 1040X, Amended U.S. Individual Income Tax Return. Amounts paid for health insurance coverage from retirement plan distributions that were nontaxable because you are a retired public safety officer cannot be used to figure the deduction. Take the deduction on Form 1040, line 29.",
"title": ""
},
{
"docid": "133072",
"text": "\"This is the best tl;dr I could make, [original](http://www.bbc.com/news/business-41095004) reduced by 91%. (I'm a bot) ***** > Sweden is the most cashless society on the planet, with barely 1% of the value of all payments made using coins or notes last year. > &quot;Some retailers thought it&#039;s easier not to accept these new forms of cash because there&#039;s learning to be done, maybe investment in cash registration machines and so-on.\"\" > Barely 1% of the value of all payments were made using coins or notes last year, compared to around 7% across the EU and in the US. Prof Arvidsson predicts that the use of cash will most likely be reduced to &quot;a very marginal payment form&quot; by 2020. ***** [**Extended Summary**](http://np.reddit.com/r/autotldr/comments/6zlwmi/why_sweden_is_close_to_becoming_a_cashless_economy/) | [FAQ](http://np.reddit.com/r/autotldr/comments/31b9fm/faq_autotldr_bot/ \"\"Version 1.65, ~208372 tl;drs so far.\"\") | [Feedback](http://np.reddit.com/message/compose?to=%23autotldr \"\"PM's and comments are monitored, constructive feedback is welcome.\"\") | *Top* *keywords*: **cash**^#1 **payment**^#2 **card**^#3 **Sweden**^#4 **Swedish**^#5\"",
"title": ""
},
{
"docid": "405919",
"text": "\"This is the best tl;dr I could make, [original](https://www.bloomberg.com/news/articles/2017-10-13/long-awaited-fed-balance-sheet-taper-begins-today-with-mortgages) reduced by 54%. (I'm a bot) ***** > After months of debate and conjecture about what&#039;s become known as the Federal Reserve&#039;s balance-sheet taper, the New York branch will announce at 3 p.m. its purchase schedule for a $4 billion per month roll off in the central bank&#039;s holdings. > The amount allowed to roll off will rise to $8 billion a month in January, to $12 billion a month in April and then ramp up in stages until it reaches a maximum of $20 billion in October 2018. > In the last schedule which ran from Sept. 28 to Oct. 13, 30-year 3.5s made up 52 percent of all the $14.75 billion of Fed purchases. ***** [**Extended Summary**](http://np.reddit.com/r/autotldr/comments/769hn5/the_longawaited_fed_balance_sheet_taper_begins/) | [FAQ](http://np.reddit.com/r/autotldr/comments/31b9fm/faq_autotldr_bot/ \"\"Version 1.65, ~227934 tl;drs so far.\"\") | [Feedback](http://np.reddit.com/message/compose?to=%23autotldr \"\"PM's and comments are monitored, constructive feedback is welcome.\"\") | *Top* *keywords*: **billion**^#1 **month**^#2 **purchase**^#3 **off**^#4 **Fed**^#5\"",
"title": ""
},
{
"docid": "150219",
"text": "\"We will bill our clients periodically and will get paid monthly. Who are \"\"we\"\"? If you're not employed - you're not the one doing the work or billing the client. Would IRS care about this or this should be something written in the policy of our company. For example: \"\"Every two months profits get divided 50/50\"\" They won't. S-Corp is a pass-through entity. We plan to use Schedule K when filing taxes for 2015. I've never filled a schedule K before, will the profit distributions be reflected on this form? Yes, that is what it is for. We might need extra help in 2015, so we plan to hire an additional employee (who will not be a shareholder). Will our tax liability go down by doing this? Down in what sense? Payroll is deductible, if that's what you mean. Are there certain other things that should be kept in mind to reduce the tax liability? Yes. Getting a proper tax adviser (EA/CPA licensed in your State) to explain to you what S-Corp is, how it works, how payroll works, how owner-shareholder is taxed etc etc.\"",
"title": ""
},
{
"docid": "191677",
"text": "10-Q is the quarterly report, and accordingly is filed quarterly. Similarly, 10-K is the annual report. 8-K is a general form for notification of material events. It is filed every time a material event is required to be reported to the shareholders. It may accompany the periodical reports, but doesn't have to. It can be filed on its own. If you're only interested in the financial statements, then you should be looking for the 10K/10Q forms. SEC will tell you when the forms were filed (dates), but it won't tell you what's more material and what's less. So you can plot a stock price graph on these dates, and see what was deemed more material by the investors based on the price fluctuations, but be prepared to find fluctuations that have no correlation to filings - because the market as a whole can drag the stock up or down. Also, some events may not be required to be reported to SEC, but may be deemed material by the investors. For example, a Cupertino town hall meeting discussing the zoning for the new AAPL HQ building may be deemed material by the investors, based on the sentiments, even if no decision was made to be reported to SEC.",
"title": ""
},
{
"docid": "561924",
"text": "Shares used to be paper documents, but these days they are more commonly held electronically instead, although this partly depends on what country you're in. But it doesn't make any significant practical difference. Regardless of their physical form, a share simply signifies that you own a certain proportion of a company, and are thus entitled to receive any dividends that may be paid to the shareholders. To sell your shares, you need a broker -- there are scores of online ones who will sell them for a modest fee. Your tax forms are entirely dependent on the jurisdiction(s) that tax you, and since you've not told us where you are, no one can answer that.",
"title": ""
},
{
"docid": "411063",
"text": "Through your question and then clarification through the comments, it looks like you have a U.S. LLC with at least two members. If you did not elect some other tax treatment, your LLC will be treated as a partnership by the IRS. The partnership should file a tax return on Form 1065. Then each partner will get a Schedule K-1 from the partnership, which the partner should use to include their respective shares of the partnership income and expenses on their personal Forms 1040. You can also elect to be taxed as an S-Corp or a C-Corp instead of a partnership, but that requires you to file a form explicitly making such election. If you go S-Corp, then you will file a different form for the company, but the procedure is roughly the same - Income gets passed through to the owners via a Schedule K-1. If you go C-Corp, then the owners will pay no tax on their own Form 1040, but the C-Corp itself will pay income tax. As far as whether you should try to spend the money as business expense to avoid paying extra tax - That's highly dependent on your specific situation. I'd think you'd want to get tailored advice for that.",
"title": ""
},
{
"docid": "590453",
"text": "If you're into math, do this thought experiment: Consider the outcome X of a random walk process (a stock doesn't behave this way, but for understanding the question you asked, this is useful): On the first day, X=some integer X1. On each subsequent day, X goes up or down by 1 with probability 1/2. Let's think of buying a call option on X. A European option with a strike price of S that expires on day N, if held until that day and then exercised if profitable, would yield a value Y = min(X[N]-S, 0). This has an expected value E[Y] that you could actually calculate. (should be related to the binomial distribution, but my probability & statistics hat isn't working too well today) The market value V[k] of that option on day #k, where 1 < k < N, should be V[k] = E[Y]|X[k], which you can also actually calculate. On day #N, V[N] = Y. (the value is known) An American option, if held until day #k and then exercised if profitable, would yield a value Y[k] = min(X[k]-S, 0). For the moment, forget about selling the option on the market. (so, the choices are either exercise it on some day #k, or letting it expire) Let's say it's day k=N-1. If X[N-1] >= S+1 (in the money), then you have two choices: exercise today, or exercise tomorrow if profitable. The expected value is the same. (Both are equal to X[N-1]-S). So you might as well exercise it and make use of your money elsewhere. If X[N-1] <= S-1 (out of the money), the expected value is 0, whether you exercise today, when you know it's worthless, or if you wait until tomorrow, when the best case is if X[N-1]=S-1 and X[N] goes up to S, so the option is still worthless. But if X[N-1] = S (at the money), here's where it gets interesting. If you exercise today, it's worth 0. If wait until tomorrow, there's a 1/2 chance it's worth 0 (X[N]=S-1), and a 1/2 chance it's worth 1 (X[N]=S+1). Aha! So the expected value is 1/2. Therefore you should wait until tomorrow. Now let's say it's day k=N-2. Similar situation, but more choices: If X[N-2] >= S+2, you can either sell it today, in which case you know the value = X[N-2]-S, or you can wait until tomorrow, when the expected value is also X[N-2]-S. Again, you might as well exercise it now. If X[N-2] <= S-2, you know the option is worthless. If X[N-2] = S-1, it's worth 0 today, whereas if you wait until tomorrow, it's either worth an expected value of 1/2 if it goes up (X[N-1]=S), or 0 if it goes down, for a net expected value of 1/4, so you should wait. If X[N-2] = S, it's worth 0 today, whereas tomorrow it's either worth an expected value of 1 if it goes up, or 0 if it goes down -> net expected value of 1/2, so you should wait. If X[N-2] = S+1, it's worth 1 today, whereas tomorrow it's either worth an expected value of 2 if it goes up, or 1/2 if it goes down (X[N-1]=S) -> net expected value of 1.25, so you should wait. If it's day k=N-3, and X[N-3] >= S+3 then E[Y] = X[N-3]-S and you should exercise it now; or if X[N-3] <= S-3 then E[Y]=0. But if X[N-3] = S+2 then there's an expected value E[Y] of (3+1.25)/2 = 2.125 if you wait until tomorrow, vs. exercising it now with a value of 2; if X[N-3] = S+1 then E[Y] = (2+0.5)/2 = 1.25, vs. exercise value of 1; if X[N-3] = S then E[Y] = (1+0.5)/2 = 0.75 vs. exercise value of 0; if X[N-3] = S-1 then E[Y] = (0.5 + 0)/2 = 0.25, vs. exercise value of 0; if X[N-3] = S-2 then E[Y] = (0.25 + 0)/2 = 0.125, vs. exercise value of 0. (In all 5 cases, wait until tomorrow.) You can keep this up; the recursion formula is E[Y]|X[k]=S+d = {(E[Y]|X[k+1]=S+d+1)/2 + (E[Y]|X[k+1]=S+d-1) for N-k > d > -(N-k), when you should wait and see} or {0 for d <= -(N-k), when it doesn't matter and the option is worthless} or {d for d >= N-k, when you should exercise the option now}. The market value of the option on day #k should be the same as the expected value to someone who can either exercise it or wait. It should be possible to show that the expected value of an American option on X is greater than the expected value of a European option on X. The intuitive reason is that if the option is in the money by a large enough amount that it is not possible to be out of the money, the option should be exercised early (or sold), something a European option doesn't allow, whereas if it is nearly at the money, the option should be held, whereas if it is out of the money by a large enough amount that it is not possible to be in the money, the option is definitely worthless. As far as real securities go, they're not random walks (or at least, the probabilities are time-varying and more complex), but there should be analogous situations. And if there's ever a high probability a stock will go down, it's time to exercise/sell an in-the-money American option, whereas you can't do that with a European option. edit: ...what do you know: the computation I gave above for the random walk isn't too different conceptually from the Binomial options pricing model.",
"title": ""
},
{
"docid": "523872",
"text": "\"This is the best tl;dr I could make, [original](https://www.bloomberg.com/amp/view/articles/2017-09-21/bet-with-buffett-not-against-him) reduced by 90%. (I'm a bot) ***** > The first is a New York Post article with the headline, &quot;Warren Buffett wins $1M bet made with hedgie a decade ago&quot;. > Although Seides has admitted defeat, he said he thinks that &quot;Doubling down on a bet with Warren Buffett for the next 10 years would hold greater-than-even odds of victory.&quot; Thus, despite spending $1 million in tuition at the University of Buffett, he failed to learn the expensive lesson that Buffett has offered up to all of us. > Which leads us to Buffett&#039;s motivation in making the bet. ***** [**Extended Summary**](http://np.reddit.com/r/autotldr/comments/725pxt/bet_with_buffett_not_against_him/) | [FAQ](http://np.reddit.com/r/autotldr/comments/31b9fm/faq_autotldr_bot/ \"\"Version 1.65, ~215707 tl;drs so far.\"\") | [Feedback](http://np.reddit.com/message/compose?to=%23autotldr \"\"PM's and comments are monitored, constructive feedback is welcome.\"\") | *Top* *keywords*: **Buffett**^#1 **bet**^#2 **money**^#3 **year**^#4 **Index**^#5\"",
"title": ""
},
{
"docid": "584627",
"text": "the whole room basically jumped on me I really have an issue with this. Someone providing advice should offer data, and guidance. Not bully you or attack you. You offer 3 choices. And I see intelligent answers advising you against #1. But I don't believe these are the only choices. My 401(k) has an S&P fund, a short term bond fund, and about 8 other choices including foreign, small cap, etc. I may be mistaken, but I thought regulations forced more choices. From the 2 choices, S&P and short term bond, I can create a stock bond mix to my liking. With respect to the 2 answers here, I agree, 100% might not be wise, but 50% stock may be too little. Moving to such a conservative mix too young, and you'll see lower returns. I like your plan to shift more conservative as you approach retirement. Edit - in response to the disclosure of the fees - 1.18% for Aggressive, .96% for Moderate I wrote an article 5 years back, Are you 401(k)o'ed in which I discuss the level of fees that result in my suggestion to not deposit above the match. Clearly, any fee above .90% would quickly erode the average tax benefit one might expect. I also recommend you watch a PBS Frontline episode titled The Retirement Gamble It makes the point as well as I can, if not better. The benefit of a 401(k) aside from the match (which you should never pass up) is the ability to take advantage of the difference in your marginal tax rate at retirement vs when earned. For the typical taxpayer, this means working and taking those deposits at the 25% bracket, and in retirement, withdrawing at 15%. When you invest in a fund with a fee above 1%, you can see it will wipe out the difference over time. An investor can pay .05% for the VOO ETF, paying as much over an investing lifetime, say 50 years, as you will pay in just over 2 years. They jumped on you? People pushing funds with these fees should be in jail, not offering financial advice.",
"title": ""
},
{
"docid": "208263",
"text": "\"A long time ago, in a galaxy far far away, Rollover IRAs were used for funds that came from (were rolled over from) a 401(k) account or a 403(b) account. All that money (including any earnings in the interim) could be rolled over into a 401(k) plan with a new employer etc. One could make a regular contribution to a Rollover IRA but once such a commingling of money occurred, none of the money in the Rollover IRA could be rolled over into a 401(k) account etc. In those good old days when contributions to IRAs were made by paper check and \"\"deposit slip\"\", one had to write a letter to the Rollover IRA custodian certifying that the IRA owner understood that the contribution would destroy forever the possibility of rolling over the money into another 401(k) etc. All this went by the wayside a few years ago when the law changed and the distinction between Rollover IRAs and ordinary Traditional IRAs was eliminated. Commingling of IRA contributions and Rollover money from 401(k)s are permitted, and the entire IRA balance could be rolled over into a new 401(k) plan (provided the new plan accepted rollovers). However the adjectives still persist; like chili555, I too have IRAs that are still called Rollover IRA, they all have commingled funds, and if the law ever changes back, none of those IRA accounts would be eligible for rolling over into a new 401(k).\"",
"title": ""
},
{
"docid": "504382",
"text": "You don't need to submit a K-1 form to anyone, but you will need to transcribe various entries on the K-1 form that you will receive onto the appropriate lines on your tax return. Broadly speaking, assets received as a bequest from someone are not taxable income to you but any money that was received by your grandmother's estate between the time of death and the time of distribution of the assets (e.g. interest, mutual fund distributions paid in cash, etc) might be passed on to you in full instead of the estate paying income tax on this income and sending you only the remainder. If so, this other money would be taxable income to you. The good news is that if the estate trust distributions include stock, your basis for the stock is the value as of the date of death (nitpickers: I am aware that the estate is allowed to pick a different date for the valuation but I am trying to keep it simple here). That is, if the stock has appreciated, your grandmother never paid capital gains on those unrealized capital gains, and you don't have to pay tax on those capital gains either; your basis is the appreciated value and if and when you sell the stock, you pay tax only on the gain, if any, between the day that Grandma passed away and the day you sell the stock.",
"title": ""
},
{
"docid": "349348",
"text": "\"I'm assuming that when you say \"\"convert to S-Corp tax treatment\"\" you're not talking about actually changing your LLC to a Corporation. There are two distinct pieces of the puzzle here. First, there's your organizational form. Your state, which is where the business is legally formed and recognized, creates the LLC or Corporation. \"\"S-Corp\"\" doesn't come into play here: your company is either an LLC or a Corporation. (There are a handful of other organizational types your state might have, e.g. PLLC, Limited Partnership, etc.; none of these are immediately relevant to this discussion). Second, there's the tax treatment you receive by the IRS. If your company was created by the state as an LLC, note that the IRS doesn't recognize LLCs as a distinct organizational type: you elect to be taxed as an individual (for single member LLCs), a partnership (for multiple member LLCs), or as a corporation. The former two elections are \"\"pass through\"\" -- there's no additional level of taxation on corporate profits, everything just passes through to the owners. The latter election introduces a tax on corporate profits. When you elect pass-through treatment, a single-member LLC files on Schedule C; a multiple-member LLC will prepare a form K-1 which you will include on your 1040. If your company was created by the state as a Corporation (not an LLC), you could still elect pass-through taxation if your company qualifies under the rules in Subchapter S (i.e. \"\"an S-Corp\"\"). States do not recognize \"\"S-Corp\"\" as part of the organizational process -- that's just a tax distinction used by the IRS (and possibly your state's tax authorities). In your case, if you are a single-member LLC (and assuming there are no other reasons to organize as a corporation), talking about \"\"S-Corp tax treatment\"\" doesn't make any sense. You'll just file your schedule C; in my experience it's fairly simple. (Note that this is based on my experience of single- and multiple-member LLCs in just two states. Your state may have different rules that affect state-level taxation; and the rules may change from year to year. I've found that hiring a good CPA to prepare the forms saves a good bit of stress and time that can be better applied to the business.)\"",
"title": ""
},
{
"docid": "421455",
"text": "\"The policy you quoted suggests you deposit 6% minimum. That $6,000 will cost you $4,500 due to the tax effect, yet after the match, you'll have $9,000 in the account. Taxable on withdrawal, but a great boost to the account. The question of where is less clear. There must be more than the 2 choices you mention. Most plans have 'too many' choices. This segues into my focus on expenses. A few years back, PBS Frontline aired a program titled The Retirement Gamble, in which fund expenses were discussed, with a focus on how an extra 1% in expenses will wipe out an extra 1/3 of your wealth in a 40 year period. Very simple to illustrate this - go to a calculator and enter .99 raised to the power of 40. .669 is the result. My 401(k) has an expense of .02% (that's 1/50 of 1%) .9998 raised to the same 40 gives .992, in other words, a cost of .8% over the full 40 years. My wife and I are just retired, and will have less in expenses for the rest of our lives than the average account cost for just 1 year. In your situation, the knee-jerk reaction is to tell you to maximize the 401(k) deposit at the current (2016) $18,000. That might be appropriate, but I'd suggest you look at the expense of the S&P index (sometime called Large Cap Fund, but see the prospectus) and if it's costing much more than .75%/yr, I'd go with an IRA (Roth, if you can't deduct the traditional IRA). Much of the value of the 401(k) beyond the match is the tax differential, i.e. depositing while in the 25% bracket, but withdrawing the funds at retirement, hopefully at 15%. It doesn't take long for the extra expense and the \"\"holy cow, my 401(k) just turned decades of dividends and long term cap gains into ordinary income\"\" effect to take over. Understand this now, not 30 years hence. Last - to answer your question, 'how much'? I often recommend what may seem a cliche \"\"continue to live like a student.\"\" Half the country lives on $54K or less. There's certainly a wide gray area, but in general, a person starting out will choose one of 2 paths, living just at, or even above his means, or living way below, and saving, say, 30-40% off the top. Even 30% doesn't hit the extreme saver level. If you do this, you'll find that if/when you get married, buy a house, have kids, etc. you'll still be able to save a reasonable percent of your income toward retirement. In response to your comment, what counts as retirement savings? There's a concept used as part of the budgeting process known as the envelope system. For those who have an income where there's little discretionary money left over each month, the method of putting money aside into small buckets is a great idea. In your case, say you take me up on the 30-40% challenge. 15% of it goes to a hard and fast retirement account. The rest, to savings, according to the general order of emergency fund, 6-12 months expenses, to cover a job loss, another fund for random expenses, such as new transmission (I've never needed one, but I hear they are expensive), and then the bucket towards house down payment. Keep in mind, I have no idea where you live or what a reasonable house would cost. Regardless, a 20-25% downpayment on even a $250K house is $60K. That will take some time to save up. If the housing in your area is more, bump it accordingly. If the savings starts to grow beyond any short term needs, it gets invested towards the long term, and is treated as \"\"retirement\"\" money. There is no such thing as Saving too much. When I turned 50 and was let go from a 30 year job, I wasn't unhappy that I saved too much and could call it quits that day. Had I been saving just right, I'd have been 10 years shy of my target.\"",
"title": ""
},
{
"docid": "289876",
"text": "\"Been to many job interviews, here's my advice: 1) What the hell the company sells, who it sells to and who the competition is. THINK about the company. What do you think they do well, what do you think they need improvement on? It's a public company so a great way to start is look at yahoo finance. You can read headlines, ready the financial statements, etc. http://finance.yahoo.com/q?s=AFG 2) What do you bring to the company? Have 5 ways to talk about how you are a great, smart person by talking about examples. Anybody can say they are smart, dedicated, etc. People want to hear examples; \"\"Past performance = future performance\"\" 3) Ask questions, a million. Goes back to #1. Know the ins and outs of the company and ask a million. Someone who asks a boat load of good questions will show they are interested, did their homework and looking to learn. Don't worry if you think it will show you don't know things...people actually want someone they can teach; not someone who is smarter than they are. (Just to be clear, don't ask about the stock or its price) 4) I have an exclusive interview tip that I will not broadcast to everyone. But if you want it, PM me.\"",
"title": ""
},
{
"docid": "210713",
"text": "No, you will not have to pay taxes on the corpus (principal) of the trust distribution. If the trust tax forms were filed correctly, you might have as much as a $9000 loss that will flow to you on the trust's termination. Previously, the trust was supposed to file a return each year, and either claim the dividends or realized cap gains each year, and pay taxes at trust's rate, or distribute them to the beneficiaries via K-1 form. This is the best way to handle this as the trust has a steep tax table (relative high rates) vs the kiddie tax which would let you get nearly $1K/yr tax free each year as a minor. During that time, losses net again gains, but can't be 'distributed' to the beneficiary. They are carried forward year to year. In the year the trust is terminated, that loss is not lost, but it's then passed on to the beneficiary, still via K-1. See Schedule K-1 instructions and Schedule K-1 itself. On a lighter note, the trustee failed you. In the 16 years (Jan 2000-Dec 2015), the market (S&P) grew by 88%, with a compound 4.02%/yr return. Instead of any gain, you got a loss with a -2.75%/yr return. If this were a paid professional, you'd have a potential claim for a lawsuit. This is a reason why amateurs should not be assigned the role of trustee. To clearly answer the mix of questions you asked - Note - it's always a good idea to seek professional advice. But, the nature of this board is that if any of my answer isn't accurate, a high ranked member (top 20 or so on this list) will likely set me straight within 24 hours.",
"title": ""
},
{
"docid": "440091",
"text": "Companies typically release their earnings before the market opens, and then later host an analyst/investor conference call to discuss the results. Here's a link to an interesting article abstract on the subject: Disclosure Rules For Earnings Releases And Calls | Bowne Digest. Excerpt: In the aftermath of the Sarbanes-Oxley Act, the SEC changed regulations to bring quarterly earnings announcements in line with the generally heightened sensitivity to adequate disclosure. New regulations required that issuers file or furnish their earnings press releases on Form 8-K and conduct any related oral presentations promptly thereafter, to avoid a second 8-K. [...] Sample from a news release by The Coca Cola Company: ATLANTA, September 30, 2009 - The Coca-Cola Company will release third quarter and year-to-date 2009 financial results on Tuesday, October 20, before the stock market opens. The Company will host an investor conference call at 9:30 a.m. ( EDT ), on October 20. [...] Sample from a news release by Apple, Inc.: CUPERTINO, California—January 21, 2009—Apple® today announced financial results for its fiscal 2009 first quarter ended December 27, 2008. The Company posted record revenue of [...] Apple will provide live streaming of its Q1 2009 financial results conference call utilizing QuickTime®, Apple’s standards-based technology for live and on-demand audio and video streaming. The live webcast will begin at [...]",
"title": ""
},
{
"docid": "566553",
"text": "The other answer has some good points, to which I'll add this: I believe you're only considering a company's Initial Public Offering (IPO), when shares are first offered to the public. An IPO is the way most companies get a public listing on the stock market. However, companies often go to market again and again to issue/sell more shares, after their IPO. These secondary offerings don't make as many headlines as an IPO, but they are typical-enough occurrences in markets. When a company goes back to the market to raise additional funds (perhaps to fund expansion), the value of the company's existing shares that are being traded is a good indicator of what they may expect to get for a secondary offering of shares. A company about to raise money desires a higher share price, because that will permit them to issue less shares for the amount of money they need. If the share price drops, they would need to issue more shares for the same amount of money – and dilute existing owners' share of the overall equity further. Also, consider corporate acquisitions: When one company wants to buy another, instead of the transaction being entirely in cash (maybe they don't have that much in the bank!), there's often an equity component, which involves swapping shares of the company being acquired for new shares in the acquiring company or merged company. In that case, the values of the shares in the public marketplace also matter, to provide relative valuations for the companies, etc.",
"title": ""
},
{
"docid": "148270",
"text": "The Art of Short Selling by Kathryn Stanley providers for many case studies about what kind of opportunities to look for from a fundamental analysis perspective. Typically things you can look for are financing terms that are not very favorable (expensive interest payments) as well as other constrictions on cash flow, arbitrary decisions by management (poor management), and dilution that doesn't make sense (usually another product of poor management). From a quantitative analysis perspective, you can gain insight by looking at the credit default swap rate history, if the company is listed in that market. The things that affect a CDS spread are different than what immediately affects share prices. Some market participants trade DOOMs over Credit Default Swaps, when they are betting on a company's insolvency. But looking at large trades in the options market isn't indicative of anything on its own, but you can use that information to help confirm your opinion. You can certainly jump on a trend using bad headlines, but typically by the time it is headline news, the majority of the downward move in the share price has already happened, or the stock opened lower because the news came outside of market hours. You have to factor in the short interest of the company, if the short interest is high then it will be very easy to squeeze the shorts resulting in a rally of share prices, the opposite of what you want. A short squeeze doesn't change the fundamental or quantitative reasons you wanted to short. The technical analysis should only be used to help you decide your entry and exit price ranges amongst an otherwise random walk. The technical rules you created sound like something a very basic program or stock screener might be able to follow, but it doesn't tell you anything, you will have to do research in the company's public filings yourself.",
"title": ""
},
{
"docid": "484149",
"text": "mhoran answered the headline question, but you asked - Could someone shed some light on and differentiate between a retirement account and alternative savings plans? Retirement accounts can contain nearly anything that one would consider an investment. (yes, there are exception, not the topic for today). So when one says they have an S&P fund or ETF, and some company issued Bonds, etc, these may or may not be held in a retirement account. In the US, when we say 'retirement account,' it means a bit more than just an account earmarked for that goal. It's an account, 401(k), 403(b), IRA, etc, that has a special tax status. Money can go in pre-tax, and be withdrawn at retirement when you are in a lower tax bracket. The Roth flavor of 401(k) or IRA lets you deposit post-tax money, and 'never' pay tax on it again, if withdrawn under specific conditions. In 2013, a single earner pays 25% federal tax on taxable earnings over $36K. But a retiree with exactly $46K in gross income (who then has $10K in standard deduction plus exemption) has a tax of $4950, less than 11% average rate on that withdrawal. This is the effect of the deductions, 10% and 15% brackets. As with your other question, there's a lot to be said about this topic, no one can answer in one post. That said, the second benefit of the retirement account is the mental partitioning. I have retirement money, not to be touched, emergency money used for the broken down car or appliance replacement, and other funds it doesn't feel bad to tap for spending, vacations, etc. Nothing a good spreadsheet can't handle, but a good way to keep things physically separate as well. (I answered as if you are in US, but the answer works if you rename the retirement accounts, eg, Canada has similar tax structure to the US.)",
"title": ""
},
{
"docid": "254245",
"text": "What's the present value of using the payment plan? In all common sense the present value of a loan is the value that you can pay in the present to avoid taking a loan, which in this case is the lump sum payment of $2495. That rather supposes the question is a trick, providing irrelevant information about the stock market. However, if some strange interpretation is required which ignores the lump sum and wants to know how much you need in the present to pay the loan while being able to make 8% on the stock market that can be done. I will initially assume that since the lender's APR works out about 9.6% per month that the 8% from the stock market is also per month, but will also calculate for 8% annual effective and an 8% annual nominal rate. The calculation If you have $x in hand (present value) and it is exactly enough to take the loan while investing in the stock market, the value in successive months is $x plus the market return less the loan payment. In the third month the loan is paid down so the balance is zero. I.e. So the present value of using the payment plan while investing is $2569.37. You would need $2569.37 to cover the loan while investing, which is more than the $2495 lump sum payment requires. Therefore, it would be advisable to make the lump sum payment because it is less expensive: If you have $2569.37 in hand it would be best to pay the lump sum and invest the remaining $74.37 in the stock market. Otherwise you invest $2569.37 (initially), pay the loan and end up with $0 in three months. One might ask, what rate of return would the stock market need to yield to make it worth taking the loan? The APR proposed by the loan can be calculated. The present value of a loan is equal to the sum of the payments discounted to present value. I.e. with ∴ by induction So by comparing the $2495 lump sum payment with $997 over 3 x monthly instalments the interest rate implied by the loan can be found. Solving for r If you could obtain 9.64431% per month on the stock market the $x cash in hand required would be calculated by This is equal to the lump sum payment, so the calculated interest is comparable to the stock market rate of return. If you could gain more than 9.64431% per month on the stock market it would be better to invest and take the loan. Recurrence Form Solving the recurrence form shows the calculation is equivalent to the loan formula, e.g. becomes v[m + 1] = (1 + y) v[m] - p where v[0] = pv where In the final month v[final] = 0, i.e. when m = 3 Compare with the earlier loan formula: s = (d - d (1 + r)^-n) / r They are exactly equivalent, which is quite interesting, (because it wasn't immediately obvious to me that what the lender charges is the mirror opposite of what you gain by investing). The present value can be now be calculated using the formula. Still assuming the 8% stock market return is per month. If the stock market yield is 8% per annum effective rate and if it is given as a nominal annual yield, 8% compounded monthly",
"title": ""
},
{
"docid": "521489",
"text": "\"If you have an S-Corp with several shareholders - you probably also have a tax adviser who suggested using S-Corp to begin with. You're probably best off asking that adviser about this issue. If you decided to use S-Corp for multiple shareholders without a professional guiding you, you should probably start looking for such a professional, or you may get yourself into trouble. That said, and reminding you that: 1. Free advice on the Internet is worth exactly what you paid for it, and 2. I'm not a tax professional or tax adviser, you should talk to a EA/CPA licensed in your state, here's this: Generally S-Corps are disregarded entities for tax purposes and their income flows to their shareholders individual tax returns through K-1 forms distributed by the S-Corp yearly. The shareholders don't have to actually withdraw the profits, but if not withdrawing - they're added to their cost bases in the shares. I'm guessing your corp doesn't distribute the net income, but keeps it on the corporate account, only distributing enough to cover the shareholders' taxes on their respective income portion. In this case - the amount not distributed is added to their basis, the amount distributed has already been taxed through K-1. If the corporation distributes more than the shareholder's portion of net income, then there can be several different choices, depending on the circumstances: The extra distribution will be treated as salary to the shareholder and a deduction to the corporation (i.e.: increasing the net income for the rest of the shareholders). The extra distribution will be treated as return of investment, reducing that shareholder's basis in the shares, but not affecting the other shareholders. If the basis is 0 then it is treated as income to the shareholder and taxed at ordinary rates. The extra distribution will be treated as \"\"buy-back\"\" - reducing that shareholder's ownership stake in the company and reallocating the \"\"bought-back\"\" portion among the rest of the shareholders. In this case it is treated as a sale of stock, and the gain is calculated as with any other stock sale, including short-term vs. long-term taxation (there's also Sec. 1244 that can come in handy here). The extra distribution will be treated as dividend. This is very rare for S-Corp, but can happen if it was a C-Corp before. In that case it will be taxed as dividends. Note that options #2, #3 and #4 subject the shareholder to the NIIT, while option #1 subjects the shareholder to FICA/Self Employment tax (and subjects the company to payroll taxes). There might be other options. Your licensed tax adviser will go with you through all the facts and circumstances and will suggest the best way to proceed.\"",
"title": ""
},
{
"docid": "453513",
"text": "\"This is the best tl;dr I could make, [original](https://www.bloomberg.com/news/articles/2017-10-23/brady-signals-retirement-changes-are-still-on-tax-writers-table) reduced by 60%. (I'm a bot) ***** > Almost 12 hours after President Donald Trump ruled out changes to 401(k) retirement-savings plans, a top congressional tax writer indicated that retirement savings remains under review. > One alternative plan would call for people to fund their retirement with after-tax earnings, but allow them to withdraw the money tax-free later on, according to Senator Rob Portman, an Ohio Republican - essentially moving toward the model for &quot;Roth&quot; individual retirement accounts. > Giant asset managers such as Vanguard Group and Fidelity Investments have said they fear that cutting 401(k) tax deferrals to just $2,400 a year would reduce the American public&#039;s notoriously low savings rate even more, jeopardizing their retirement income. ***** [**Extended Summary**](http://np.reddit.com/r/autotldr/comments/78ovy5/brady_signals_retirement_changes_are_still_on/) | [FAQ](http://np.reddit.com/r/autotldr/comments/31b9fm/faq_autotldr_bot/ \"\"Version 1.65, ~234978 tl;drs so far.\"\") | [Feedback](http://np.reddit.com/message/compose?to=%23autotldr \"\"PM's and comments are monitored, constructive feedback is welcome.\"\") | *Top* *keywords*: **save**^#1 **retirement**^#2 **tax**^#3 **accounts**^#4 **income**^#5\"",
"title": ""
},
{
"docid": "122607",
"text": "\"This is the best tl;dr I could make, [original](http://www.businessinsider.com/basic-income-would-grow-gdp-by-trillions-study-finds-2017-8) reduced by 81%. (I'm a bot) ***** > Conducted by the left-leaning Roosevelt Institute, the study investigated three strategies for implementing basic income, a form of wealth distribution that involves giving everyone a standard salary just for being alive. > Proponents of basic income say it would reduce or even eliminate poverty, while skeptics say it could erase people&#039;s motivations to keep working, possibly ruining the economy instead of improving it. > The three basic incomes proposed by the study were $1,000 paid monthly to every US adult; $500 paid monthly to every US adult; and $250 paid monthly to every US child. ***** [**Extended Summary**](http://np.reddit.com/r/autotldr/comments/6zfh4r/giving_every_american_12000_a_year_in_free_money/) | [FAQ](http://np.reddit.com/r/autotldr/comments/31b9fm/faq_autotldr_bot/ \"\"Version 1.65, ~207966 tl;drs so far.\"\") | [Feedback](http://np.reddit.com/message/compose?to=%23autotldr \"\"PM's and comments are monitored, constructive feedback is welcome.\"\") | *Top* *keywords*: **basic**^#1 **income**^#2 **study**^#3 **year**^#4 **every**^#5\"",
"title": ""
},
{
"docid": "271772",
"text": "Since you both are members of the LLC - it is not a single-member LLC, thus you have to file the tax return on behalf of the LLC (I'm guessing you didn't elect corporate treatment, so you would be filing 1065, which is the default). You need to file form 4868 on behalf of yourselves as individuals, and form 7004 on behalf of the LLC as the partnership. Since the LLC is disregarded (unless you explicitly chose it not to be, which seems not to be the case) the taxes will in fact flow to your individual return(s), but the LLC will have to file the informational return on form 1065 and distribute K-1 forms to each of you. So you wouldn't pay additional estimated taxes with the extension, as you don't pay any taxes with the form 1065 itself. If you need a help understanding all that and filling the forms - do talk to a professional (EA or CPA licensed in your state). Also, reconsider not sending any payment. I suggest sending $1 with the extension form even if you expect a refund.",
"title": ""
},
{
"docid": "453714",
"text": "\"This is the best tl;dr I could make, [original](https://www.vox.com/policy-and-politics/2017/8/18/16162234/regional-inequality-cause) reduced by 89%. (I'm a bot) ***** > In the contemporary United States, zoning restrictions that prevent adequate levels of house building mean that much of the higher incomes earned in rich states simply pass through in the form of higher housing costs. > Two big shifts in migration and economics This set of four charts in Ganong and Shoag&#039;s paper tells the fundamental story - in the old days, there was a strong tendency for poor states&#039; per capita incomes to grow faster than those of rich ones and an equally strong tendency for people to move away from poor states to go live in rich ones. > The housing fix for regional inequality entails more rather than less concentration of economic activity in rich coastal metro areas. ***** [**Extended Summary**](http://np.reddit.com/r/autotldr/comments/6ujy5s/the_real_driver_of_regional_inequality_in_america/) | [FAQ](http://np.reddit.com/r/autotldr/comments/31b9fm/faq_autotldr_bot/ \"\"Version 1.65, ~194007 tl;drs so far.\"\") | [Feedback](http://np.reddit.com/message/compose?to=%23autotldr \"\"PM's and comments are monitored, constructive feedback is welcome.\"\") | *Top* *keywords*: **state**^#1 **rich**^#2 **income**^#3 **move**^#4 **housing**^#5\"",
"title": ""
},
{
"docid": "42501",
"text": "\"This is the best tl;dr I could make, [original](https://www.bloomberg.com/news/articles/2017-07-30/trump-s-dollar-mess-losses-pile-up-as-political-drama-mounts) reduced by 90%. (I'm a bot) ***** > The dollar soared in November before ending the year at the highest since at least 2005, according to the Bloomberg Dollar Spot Index, which tracks the greenback versus 10 global currencies. > While the stock market has rallied to new highs as equity investors looked past politics and focused on corporate earnings, the dollar has slumped more than 8 percent, wiping out the post-election bump and then some. > &quot;Look at how the dollar moved up when it was felt that the Trump election was going to lead to happy days again,&quot; Snow said. ***** [**Extended Summary**](http://np.reddit.com/r/autotldr/comments/6qoujg/stocks_are_at_all_time_highs_but_the_dollar_is/) | [FAQ](http://np.reddit.com/r/autotldr/comments/31b9fm/faq_autotldr_bot/ \"\"Version 1.65, ~179908 tl;drs so far.\"\") | [Feedback](http://np.reddit.com/message/compose?to=%23autotldr \"\"PM's and comments are monitored, constructive feedback is welcome.\"\") | *Top* *keywords*: **dollar**^#1 **currency**^#2 **market**^#3 **Trump**^#4 **more**^#5\"",
"title": ""
},
{
"docid": "171144",
"text": "\"This is the best tl;dr I could make, [original](https://www.bloomberg.com/news/articles/2017-09-29/who-s-left-out-of-401-k-nation) reduced by 50%. (I'm a bot) ***** > Only 45 percent of U.S. workers participate in an employer-sponsored retirement plan, according to the Pew Charitable Trusts. > Groups with the highest percentages of workers without access to a plan:Part-Timers: 56 percent, vs. 31 percent of full-timers without accessHispanics: 55 percent, vs. 32 percent for whites and 36 percent for blacksMillennials: 45 percent, vs. 30 percent of baby boomers and 35 percent of Gen Xers. > The Oregon IRA● OregonSaves starts on Oct. 15, initially targeting workers at 2,100 of the state&#039;s largest employers● Workers will save 5 percent of their incomes unless they opt out or adjust the percentage● About 200,000 self-employed workers will have the option to enroll by the end of 2018● 77 percent of workers who participated in a pilot program are opting to remain enrolled. ***** [**Extended Summary**](http://np.reddit.com/r/autotldr/comments/73d3r4/whos_left_out_of_401k_nation/) | [FAQ](http://np.reddit.com/r/autotldr/comments/31b9fm/faq_autotldr_bot/ \"\"Version 1.65, ~219383 tl;drs so far.\"\") | [Feedback](http://np.reddit.com/message/compose?to=%23autotldr \"\"PM's and comments are monitored, constructive feedback is welcome.\"\") | *Top* *keywords*: **percent**^#1 **workers**^#2 **plan**^#3 **retirement**^#4 **employer**^#5\"",
"title": ""
},
{
"docid": "482768",
"text": "There are a few incorrect assumptions in your question but the TL;DR version is: All, or most, of the withdrawal is taxable income that is reported on Lines 15a (total distribution) and 15b (taxable amount) of Form 1040. None of the distribution is given special treatment as Qualified Dividends or Capital Gains regardless of what happened inside the IRA, and none of the distribution is subject to the 3.8% Net Investment Income Tax that some high-income people need to compute on Form 8960. If the withdrawal is not a Qualified Distribution, it will be subject to a 10% excise tax (tax penalty on premature withdrawal). Not all contributions to Traditional IRAs are deductible from income for the year for which the contribution was made. People with high income and/or coverage by a workplace retirement plan (pension plan, 401(k) plan, 403(b) plan, etc) cannot deduct any contributions that they choose to make to a Traditional IRA. Such people can always make a contribution (subject to them having compensation (earned income such as salary or wages, self-employment income, commissions on sales, etc), but they don't get a tax deduction for it (just as contributions to Roth IRAs are not deductible). Whether it is wise to make such nondeductible contributions to a Traditional IRA is a question on which reasonable people can hold different opinions. Be that as it may, nondeductible contributions to a Traditional IRA create (or add to) what is called the basis of an IRA. They are reported to the IRS on Form 8606 which is attached to the Federal Form 1040. Note that the IRA custodian or trustee is not told that the contributions are not deductible. Earnings on the basis accumulate tax-deferred within the IRA just as do the earnings on the deductible contributions. Now, when you make a withdrawal from your Traditional IRA, no matter which of your various IRA accounts you take the money from, part of the money is deemed to be taken from the basis (and is not subject to income tax) while the rest is pure taxable income. That is, none of the rest is eligible for the reduced taxation rates for Qualified Dividends or Capital Gains and since it does not count as investment income, it is not subject to the 3.8% Net Investment Tax of Form 8960 either. Computation of how much of your withdrawal is nontaxable basis and how much is taxable income is done on Form 8606. Note that you don't get to withdraw your entire basis until such time as when you close all your Traditional IRA accounts. How is all this reported? Well, your IRA custodian(s) will send you Form 1099-R reporting the total amount of the withdrawal, what income tax, if any, was withheld, etc. The custodian(s) don't know what your basis is, and so Box 2b will say that the taxable amount is not determined. You need to fill out Form 8606 to figure out what the taxable amount is, and then report the taxable amount on Line 15b of Form 1040. (The total withdrawal is reported on Line 15a which is not included in the AGI computations). Note that as far as the IRS is concerned, you have only one Traditional IRA. The A in IRA stands for Arrangement, not Account as most everybody thinks, and your Traditional IRA can invest in many different things, stocks, bonds, mutual funds, etc with different custodians if you choose, but your basis is in the IRA, not the specific investment that you made with your nondeductible contribution. That's why the total IRA contribution is limited, not the per-account contribution, and why you need to look that the total value of your IRA in determining the taxable portion, not the specific account(s) from which you withdrew the money. So, how much basis did you withdraw? Well, if you withdrew $W during 2016 and the total value of all your Traditional IRA accounts was $X at the end of 2016 and your total basis in your Traditional IRA is $B, then (assuming that you did not indulge in any Traditional-to-Roth rollovers for 2016), multiply W by B/(W+X) to get the amount of nontaxable basis in the withdrawal. B thus gets reduced for 2017 by amount of basis withdrawal. What if you never made a nondeductible contribution to your Traditional IRA, or you made some nondeductible contributions many years ago and have forgotten about them? Well, you could still fill out Form 8606 reporting a zero basis, but it will just tell you that your basis continues $0. Or, you could just enter the total amount of your withdrawal in Lines 15a and 15b, effectively saying that all of the withdrawal is taxable income to you. The IRS does not care if you choose to pay taxes on nontaxable income.",
"title": ""
}
] |
5ac2703455429951e9e685c6
|
which American guitaris was Famous Monsters last to feature
|
[
{
"docid": "3037699",
"text": "Doyle Wolfgang von Frankenstein (born Paul Caiafa on September 15, 1964 in Lodi, New Jersey) is an American guitarist best known for his material with the horror punk band the Misfits and his own band eponymously named Doyle.",
"title": ""
},
{
"docid": "2133718",
"text": "Famous Monsters is a 1999 album by the Misfits. It is the second in the \"post-Danzig\" era of the band, and the last album to feature Doyle Wolfgang von Frankenstein, Michale Graves, and Dr. Chud, who would all quit the band in 2000.",
"title": ""
}
] |
[
{
"docid": "3303351",
"text": "House of Dracula is a 1945 American monster crossover horror film released by Universal Pictures. It was a direct sequel to \"House of Frankenstein\", and continued the theme of combining Universal's three most popular monsters: Frankenstein's monster (Glenn Strange), Count Dracula (John Carradine), and the Wolf Man (Lon Chaney Jr.). The film, which was the seventh Universal film to feature Frankenstein's monster, as well as the fourth with Count Dracula and the Wolf Man, was a commercial success, but was one of the last Universal movies featuring Frankenstein's monster, vampires, and werewolves, with the exception of the comedy \"Abbott and Costello Meet Frankenstein\" (1948), in which all three appear.",
"title": ""
},
{
"docid": "43791894",
"text": "Milking the Stars: A Re-Imagining of Last Patrol is the tenth studio album by the American stoner rock band Monster Magnet. According to the band's frontman Dave Wyndorf, the album is a \"reimagined\" version of their previous album, 2013's \"Last Patrol\", featuring four new songs and two live tracks. The album is not strictly a remix of \"Last Patrol\"; songs feature new recordings and arrangements aimed at giving the album what Wyndorf describes as \"a weird 1960s vibe\". The album closes with two live tracks which were recorded at the AB in Brussels in 2014, and which feature the debut performance of the band's new bassist, Chris Kosnik.",
"title": ""
},
{
"docid": "11400261",
"text": "The Monster Times was a horror film fan magazine created in 1972. Published by The Monster Times Publishing Co., it was intended as a competitor to \"Famous Monsters of Filmland\". Although the main editorial focus of the magazine was horror media, it also featured articles and reviews of modern and classic science fiction/fantasy movies and television series, as well as comic books. Each issue featured a fold-out centerfold poster usually based on that particular issue's feature story.",
"title": ""
},
{
"docid": "7451198",
"text": "Basil Gogos (March 12, 1929 – September 13, 2017) was an American illustrator best known for his portraits of movie monsters which appeared on the covers of \"Famous Monsters of Filmland\" magazine in the 1960s and 1970s.",
"title": ""
},
{
"docid": "1334520",
"text": "Famous Monsters of Filmland is an American genre-specific film magazine, started in 1958 by publisher James Warren and editor Forrest J Ackerman.",
"title": ""
},
{
"docid": "47842662",
"text": "American Gothic Press is an American comic book imprint of \"Famous Monsters of Filmland\" magazine. Established in the spring of 2015, it focuses predominantly in the Kaiju, Sci-Fi, fantasy, and horror genres, reflecting Honorary \"Famous Monsters\" Editor-in-Chief Forrest J Ackerman’s love for all things monstrous and mysterious.",
"title": ""
},
{
"docid": "40810313",
"text": "Last Patrol is the ninth studio album by the American stoner rock band Monster Magnet. It is the first recording since their 1991 debut album \"Spine of God\" not to feature long time member Ed Mundell who left the band shortly after their 2010 album \"Mastermind\".",
"title": ""
},
{
"docid": "6143389",
"text": "\"Halleluhwah\" is a song by the krautrock band Can, on their 1971 album \"Tago Mago\". The track, which originally took up a whole side of long-playing vinyl record, lasts for 18 minutes and 28 seconds and is characteristic of the band's sound around 1971 in that it features a vast array of improvised guitars and keyboards, tape editing, and the rhythm section \"pounding out a monster trance/funk beat\". The drum beat for which the song is famous is repeated almost continuously by Jaki Liebezeit, with only minor variations, throughout the course of the 18-minute jam. In one line of the song, Damo Suzuki's lyrics mention all the songs from side one of \"Tago Mago\": \"mushroom head, oh yeah, paper house.\"",
"title": ""
},
{
"docid": "19394183",
"text": "Monster Rancher Battle Card GB (モンスターファームバトルカードGB , Monster Farm Battle Card GB ) is a handheld game released in 1999 for the Nintendo Game Boy Color system. It is the first game in Tecmo's \"Monster Rancher Battle Card\" series, featuring a card game incorporating the popular characters from the \"Monster Rancher\" series. It was followed by \"Monster Rancher Battle Card: Episode II\" for the Sony PlayStation entertainment system which featured additional monsters.",
"title": ""
},
{
"docid": "3672010",
"text": "The Toyes are an American reggae band based in Grants Pass, Oregon. Their style has been described as a \"cross between Bob Marley and Barenaked Ladies\". They are perhaps most famous as the original songwriters and recorders of the song \"Smoke Two Joints\". It was originally recorded in 1983, and was re-released on their 1993 debut album \"The Toyes\". It was featured on the soundtrack for the 1998 American comedy-thriller film \"Homegrown\". An influential version was recorded by the band Sublime; the song has since been mistakenly attributed to them or to Bob Marley. \"The Toyes\" also wrote and performed a song called \"Monster Hash\", a parody of Bobby \"Boris\" Pickett's \"Monster Mash\".",
"title": ""
},
{
"docid": "27602393",
"text": "Monsters is a 2010 British science fiction monster film written and directed by Gareth Edwards in his feature film directorial debut. Edwards also served as the cinematographer, production designer, and visual effects artist. \"Monsters\" takes place years after a NASA probe crash in Mexico which led to the sudden appearance of giant tentacled monsters. It follows Andrew Kaulder (Scoot McNairy), an American photojournalist tasked with escorting his employer's daughter Samantha Wynden (Whitney Able) back to the US by crossing through Mexico's \"Infected Zone\" where the creatures reside.",
"title": ""
},
{
"docid": "13639379",
"text": "B'z Live-Gym 2006 \"Monster's Garage\" is the sixth live VHS/DVD released by Japanese rock duo B'z. It features live footage of the Monster Live-Gym 2006, one of their famous Live Gyms. On December 22, 2010, the first two discs were re-released in Blu-ray. The Blu-ray release also contain the documentary disc but still in DVD.",
"title": ""
},
{
"docid": "2150451",
"text": "Kaiju Booska (快獣ブースカ , Kaijū Būsuka , translated as \"Monster Booska\") is a famous children's sitcom, and the first to feature the friendly monster Booska. Produced by Tsuburaya Productions, the show aired on Nippon TV from November 9, 1966 to September 27, 1967, with a total of 47 episodes.",
"title": ""
},
{
"docid": "2986991",
"text": "Daniel \"Dan\" Gerson (August 1, 1966 – February 6, 2016) was an American screenwriter and voice actor, best known for his work with Pixar and Walt Disney Animation Studios. He co-wrote the screenplays of \"Monsters, Inc.\", \"Monsters University\" and \"Big Hero 6\", which was reported to be his last film as screenwriter.",
"title": ""
},
{
"docid": "3618491",
"text": "Irwin Caplan (May 24, 1919 – February 22, 2007), nicknamed Cap, was an American illustrator, painter, designer and cartoonist, best known as the creator of \"The Saturday Evening Post\" cartoon series, \"Famous Last Words\", which led to newspaper syndication of the feature in 1956.",
"title": ""
},
{
"docid": "1134216",
"text": "Some Kind of Monster is a 2004 American documentary film featuring the American thrash metal band Metallica. It shares its name with the song \"Some Kind of Monster\" from Metallica's 2003 album \"St. Anger.\" The film shows many studio rehearsals and fragments of concert footage. It won the Independent Spirit Award for Best Documentary Feature. The DVD release was handled by Paramount Pictures, whose 2000 film \"\" featured \"I Disappear\" by Metallica.",
"title": ""
},
{
"docid": "10550678",
"text": "Dragon Warrior Monsters 2, known in Japan as Dragon Quest Monsters 2 (ドラゴンクエストモンスターズ , Doragon Kuesuto Monsutāzu Tsū ) , is a role-playing video game published by Enix for the Game Boy Color. It is the second \"Dragon Warrior Monsters\" game for the Game Boy Color and features two different versions of the same game, \"Cobi's Journey\" (released as \"Dragon Quest Monsters 2: Ruka's Journey\" in Japan) and \"Tara's Adventure\" (released as \"Dragon Quest Monsters 2: Iru's Adventure\" in Japan). This was the last Game Boy Color title released in North America that was also compatible with the original Game Boy and enhanced for the Super Game Boy.",
"title": ""
},
{
"docid": "31895855",
"text": "\"Monster\" is a song by American rock band Paramore. It was released on June 7, 2011 for digital download. It is also the second single from the , which was released on June 14, 2011. It is the first song to not feature former band members Josh and Zac Farro, who separated from the band in 2010.",
"title": ""
},
{
"docid": "31148191",
"text": "\"My Last\" is the first single by American rapper Big Sean from his debut album \"Finally Famous\". The song features R&B singer Chris Brown. The song is produced by No I.D..",
"title": ""
},
{
"docid": "46976587",
"text": "Il colombre is a 1966 short story collection by the Italian writer Dino Buzzati. The titular story introduces a sea monster called the colomber, which became the most famous of Buzatti's monster characters.",
"title": ""
},
{
"docid": "11592679",
"text": "The Nee Brothers, Aaron and Adam, are an American filmmaking team most famous for their feature \"The Last Romantic\".",
"title": ""
},
{
"docid": "41347310",
"text": "Nothing Cool was an American punk rock band from Phoenix, Arizona (later relocating to San Francisco) in 1994. The band was formed in 1990 by vocalist/guitaris J-Cool and guitarist Justin Berg.",
"title": ""
},
{
"docid": "13819572",
"text": "Monster Ballads: Platinum Edition is a compilation album. It features many power ballads, most of which appeared on previous \"Monster Ballads\" installations or related albums.",
"title": ""
},
{
"docid": "5308754",
"text": "Monster Truck Challenge, originally known as Powertrax, was a half-hour weekly television show on ESPN, which featured primarily tractor pulling and monster truck racing.",
"title": ""
},
{
"docid": "9269204",
"text": "This is an alphabetical list of films featuring giant monsters, known in Japan as kaiju. One of the first films involving giant monsters was the 1933 classic \"King Kong\", as developments in cinema and animation enabled the creation of realistic giant creatures. The film influenced many giant-monster films in its wake, including many produced in Japan, starting with the adaptation \"King Kong Appears in Edo\" in 1938, which is now presumed to be a lost film. The visual effects in \"King Kong\", created by Willis O'Brien, inspired future monster film effects artists such as Ray Harryhausen and Dennis Muren. Early giant-monster films often had themes of adventure and exploration of unknown regions, and incorporated fights with giant monsters as a climactic element.",
"title": ""
},
{
"docid": "5293771",
"text": "\"The Next Episode\" is a single by American rapper Dr. Dre, released on July 4, 2000 as the third single from his second studio album, \"2001\", which was released in 1999. The track features Snoop Dogg, Kurupt, and Nate Dogg, the last being uncredited. It is a sequel to Dre's famous single from \"The Chronic\", \"Nuthin' but a 'G' Thang\".",
"title": ""
},
{
"docid": "46687604",
"text": "Steph Honde (born Stéphane Honde; 5 September 1975) is a French singer, songwriter and multi-instrumentalist (vocals, guitar, piano, bass guitar). Honde is most famous for being the frontman and songwriter of the American hard rock supergroup, Hollywood Monsters which he founded in 2013. Before Hollywood Monsters, Honde was the guitarist of the French rock band from 2004 to 2010, when he resigned from the band and joined Paul Di'Anno band as the guitarist on tour across France.",
"title": ""
},
{
"docid": "4435357",
"text": "This is a list of Beetleborgs monsters featured in both versions of the American children's television series.",
"title": ""
},
{
"docid": "3729539",
"text": "Monsters is a 1989 album by the Meat Puppets. Their last release on SST Records, it was reissued on Rykodisc in 1999 with additional bonus tracks, recording notes by Derrick Bostrom and liner notes by music journalist Mark Kemp. As an added bonus, the reissue includes an \"Enhanced CD\" partition for play on home computers. \"Monsters\" offers the promotional video for \"Light\". The clip was produced and directed by Bill Taylor and features shots of the Puppets live in concert.",
"title": ""
},
{
"docid": "10812453",
"text": "Monsters vs. Aliens is a 2009 American 3D computer-animated science fiction film produced by DreamWorks Animation and distributed by Paramount Pictures. It was DreamWorks Animation's first feature film to be directly produced in a stereoscopic 3-D format instead of being converted into 3-D after completion, which added $15 million to the film's budget.",
"title": ""
}
] |
PLAIN-961
|
corn
|
[
{
"docid": "MED-3000",
"text": "An increased risk for colorectal cancer has been consistently reported for long-time consumption of cooked and processed red meat. This has frequently been attributed to chemical carcinogens arising during the cooking process of meat. Long-time fish or poultry consumption apparently does not increase the risk, although similar or higher concentrations of chemical carcinogens were recorded in their preparation for consumption. The geographic epidemiology of colorectal cancer seems to correspond to regions with a high rate of beef consumption. Countries with a virtual absence of beef in the diet (India) or where preferably lamb or goat meat is consumed (several Arabic countries) reveal low rates of colorectal cancer. In China, pork consumption has a long tradition, with an intermediate colorectal cancer rate. In Japan and Korea, large scale beef and pork imports started after World War II or after the Korean War. A steep rise in colorectal cancer incidence was noted after 1970 in Japan and 1990 in Korea. The consumption of undercooked beef (e.g., shabu-shabu, Korean yukhoe and Japanese yukke) became very popular in both countries. The available data are compatible with the interpretation that a specific beef factor, suspected to be one or more thermoresistant potentially oncogenic bovine viruses (e.g., polyoma-, papilloma- or possibly single-stranded DNA viruses) may contaminate beef preparations and lead to latent infections in the colorectal tract. Preceding, concomitant or subsequent exposure to chemical carcinogens arising during cooking procedures should result in increased risk for colorectal cancer synergistic with these infections. Copyright © 2011 UICC.",
"title": "Red meat consumption and cancer: reasons to suspect involvement of bovine infectious factors in colorectal cancer."
},
{
"docid": "MED-2150",
"text": "Previous investigations, of adolescent diet recalled in adulthood, found lower risk for benign breast disease (BBD) with higher intakes of vegetable fat and nuts during high school. We investigate whether vegetable protein and fat, derived from diets reported during pre-adolescence and adolescence, are associated with subsequent risk for BBD in young women. The Growing Up Today Study includes 9,039 females, 9–15 years in 1996, who completed questionnaires annually through 2001, and then in 2003, 2005, 2007, and 2010. Food frequency questionnaires (1996–2001) obtained intake data on a variety of foods. Beginning in 2005, women (18–30 years) reported whether they had ever been diagnosed with BBD that was confirmed by breast biopsy (n = 112 cases). Logistic regression estimated associations between intakes of vegetable protein and fat and biopsy-confirmed BBD. Those individual foods that were the largest contributors of protein and fat in this cohort were also investigated. In analyses of intakes from 1996 through 1998, when our cohort was youngest, vegetable fat (OR = 0.72/(10 gm/day), 95 % CI 0.53–0.98; p = 0.04) was inversely associated with BBD risk. The greatest sources of vegetable fat and protein in these girls were peanut butter, peanuts, nuts, beans (beans, lentils, and soybeans), and corn. A daily serving of any one of these was associated with lower risk (OR = 0.32/(serv/day), 95 % CI 0.13–0.79; p = 0.01). Peanut butter (and nuts) at age 11 years was inversely associated with risk (p = 0.01). In analyses of intakes at age 14 years, vegetable protein was associated with lower BBD risk (OR = 0.64/(10 gm/day), 95 % CI 0.43–0.95; p = 0.03). A daily serving at 14 years of any one of the foods was associated with lower risk (OR = 0.34, 95 % CI 0.16–0.75; p = 0.01), as was peanut butter (and nuts) (p = 0.02). Girls with a family history of breast cancer had significantly lower risk if they consumed these foods or vegetable fat. In conclusion, consumption of vegetable protein, fat, peanut butter, or nuts by older girls may help reduce their risk of BBD as young women.",
"title": "Vegetable protein and vegetable fat intakes in pre-adolescent and adolescent girls, and risk for benign breast disease in young women"
},
{
"docid": "MED-4687",
"text": "Vegetarian diets are rich in antioxidant phytochemicals. However, they may not act as antioxidants in vivo, and yet still have important signaling and regulatory functions. Some may act as pro-oxidants, modulating cellular redox tone and oxidizing redox sensitive sites. In this review, evidence for health benefits of vegetarian diets is presented from different perspectives: epidemiological, biomarker, evolutionary, and public health, as well as antioxidant. From the perspective of molecular connections between diet and health, evidence of a role for plasma ascorbic acid as a biomarker for future disease risk is presented. Basic concepts of redox-based cell signaling are presented, and effects of antioxidant phytochemicals on signaling, especially via redox tone, sulfur switches and the Antioxidant Response Element (ARE), are explored. Sufficient scientific evidence exists for public health policy to promote a plant-rich diet for health promotion. This does not need to wait for science to provide all the answers as to why and how. However, action and interplay of dietary antioxidants in the nonequilibrium systems that control redox balance, cell signaling, and cell function provide rich ground for research to advance understanding of orthomolecular nutrition and provide science-based evidence to advance public health in our aging population.",
"title": "Vegetarian diets and public health: biomarker and redox connections."
},
{
"docid": "MED-2884",
"text": "Two carotenoids found in egg yolk, lutein and zeaxanthin, accumulate in the macular retina where they may reduce photostress. Increases in serum lutein and zeaxanthin were observed in previous egg interventions, but no study measured macular carotenoids. The objective of this project was to determine whether increased consumption of eggs would increase retinal lutein and zeaxanthin, or macular pigment. Twenty-four females, between 24 and 59 y, were assigned to a pill treatment (PILL) or 1 of 2 egg treatments for 12 wk. Individuals in the PILL treatment consumed 1 sugar-filled capsule/d. Individuals in the egg treatments consumed 6 eggs/wk, containing either 331 microg (EGG 1) or 964 microg (EGG 2) of lutein and zeaxanthin/yolk. Serum cholesterol, serum carotenoids, and macular pigment OD (MPOD) were measured at baseline and after 4, 8, and 12 wk of intervention. Serum cholesterol concentrations did not change in either egg treatment group, but total cholesterol (P = 0.04) and triglycerides (P = 0.02) increased in the PILL group. Serum zeaxanthin, but not serum lutein, increased in both the EGG 1 (P = 0.04) and EGG 2 (P = 0.01) groups. Likewise, MPOD increased in both the EGG 1 (P = 0.001) and EGG 2 (P = 0.049) groups. Although the aggregate concentration of carotenoid in 1 egg yolk may be modest relative to other sources, such as spinach, their bioavailability to the retina appears to be high. Increasing egg consumption to 6 eggs/wk may be an effective method to increase MPOD.",
"title": "A 12-wk egg intervention increases serum zeaxanthin and macular pigment optical density in women."
},
{
"docid": "MED-1752",
"text": "The transforming growth factor-beta (TGF-beta) superfamily encompasses a large group of growth and differentiation factors playing important roles in regulating embryonic development and in maintaining tissue homeostasis in adult animals. Using degenerate polymerase chain reaction, we have identified a new murine TGF-beta family member, growth/differentiation factor-8 (GDF-8), which is expressed specifically in developing and adult skeletal muscle. During early stages of embryogenesis, GDF-8 expression is restricted to the myotome compartment of developing somites. At later stages and in adult animals, GDF-8 is expressed in many different muscles throughout the body. To determine the biological function of GDF-8, we disrupted the GDF-8 gene by gene targeting in mice. GDF-8 null animals are significantly larger than wild-type animals and show a large and widespread increase in skeletal muscle mass. Individual muscles of mutant animals weigh 2-3 times more than those of wild-type animals, and the increase in mass appears to result from a combination of muscle cell hyperplasia and hypertrophy. These results suggest that GDF-8 functions specifically as a negative regulator of skeletal muscle growth.",
"title": "Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member."
},
{
"docid": "MED-2152",
"text": "Walnuts contain bioactive molecules that may contribute to their beneficial effects, including alpha-linolenic acid (ALA) and phytosterols. In these studies, extracts of walnut, purified compounds, or postprandial serum were examined for effects on breast cancer cell proliferation and gene expression. Extracts derived from walnut oil decreased proliferation of MCF-7 cells, as did ALA and β-sitosterol. The gene expression response of ALA in the mouse breast cancer cell line TM2H indicates this molecule has multiple cellular targets with peroxisome proliferator-activated receptor (PPAR) target genes, liver X receptor (LXR), and farnesoid X receptor (FXR) target genes being affected. In transactivation assays, walnut oil extracts increased activity of FXR to a greater extent than the other tested nuclear receptors. When examined separately, walnut components ALA and β-sitosterol were the most efficacious activators of FXR. When serum from individuals fed walnut components were applied to MCF-7 cells, there was a correlation between body mass index and breast cancer cell proliferation in vitro. Taken together, these data support an effect of walnut and its bioactive constituents on mammary epithelial cells and that multiple molecular targets may be involved.",
"title": "Mechanistic examination of walnuts in prevention of breast cancer."
},
{
"docid": "MED-2891",
"text": "BACKGROUND: Patients who report use of herbs to their physicians may not be able to accurately describe the ingredients or recommended dosage because the products for the same herb may differ. The purpose of this study was to describe variations in label information of products for each of the 10 most commonly purchased herbs. METHODS: Products for each of 10 herbs were surveyed in a convenience sample of 20 retail stores in a large metropolitan area. Herbs were those with the greatest sales dollars in 1998: echinacea, St John's wort, Ginkgo biloba, garlic, saw palmetto, ginseng, goldenseal, aloe, Siberian ginseng, and valerian. RESULTS: Each herb had a large range in label ingredients and recommended daily dose (RDD) across available products. Strengths were not directly comparable because of ingredient variability. Among 880 products, 43% were consistent with a benchmark in ingredients and RDD, 20% in ingredients only, and 37% were either not consistent or label information was insufficient. Price per RDD was a significant predictor of consistency with the benchmark, but store type was not. CONCLUSIONS: Persons self-medicating with an herb may be ingesting ingredients substantially different from that recommended by a benchmark, both in quantity and content. Higher price per label RDD was the best predictor of consistency with a benchmark. This study demonstrates that health providers and consumers need to closely examine label ingredients of presumably the same or similar herbal products.",
"title": "Variations in product choices of frequently purchased herbs: caveat emptor."
},
{
"docid": "MED-2890",
"text": "Myopia is a worldwide public health problem. However, its understanding is incomplete, and many of its preventative and therapeutic aspects remain controversial. Nearwork is a primary, environmentally based factor in the aetiology of permanent myopia (PM), with nearwork-induced transient myopia (NITM) being a possible contributory component. A relationship between PM and NITM has been suggested, but that connection has remained somewhat indirect and elusive. However, based on recent converging evidence from clinical, laboratory and modelling studies, a five-fold argument will be advanced for a possible link between PM and NITM.",
"title": "Nearwork-induced transient myopia (NITM) and permanent myopia--is there a link?"
},
{
"docid": "MED-2886",
"text": "PURPOSE: Goji berry (Lycium barbarum L.) is purported to benefit vision because of its high antioxidant (especially zeaxanthin) content, although this effect has not been demonstrated in high-quality human studies. The purpose of this study was to evaluate the effects of daily supplementation with a proprietary milk-based formulation of goji berry, Lacto-Wolfberry (LWB), on macular characteristics and plasma zeaxanthin and antioxidant capacity levels in elderly subjects. METHODS: This was a double-masked, randomized, placebo-controlled trial in healthy elderly subjects (range, 65 to 70 years) receiving 13.7 g/d of LWB (n = 75) or placebo (n = 75) for 90 days. Subjects underwent direct ophthalmic examination to assess pigmentation and soft drusen count in the macula and a blood draw to measure plasma zeaxanthin level and total antioxidant capacity. RESULTS: The placebo group demonstrated hypopigmentation and soft drusen accumulation in the macula, whereas the LWB group remained stable. Both plasma zeaxanthin level and antioxidant capacity increased significantly in the LWB group, by 26% and 57%, respectively, but did not change in the placebo group. No product-related adverse events were reported in either group. CONCLUSIONS: Overall, daily dietary supplementation with goji berry for 90 days increases plasma zeaxanthin and antioxidant levels as well as protects from hypopigmentation and soft drusen accumulation in the macula of elderly subjects. However, the mechanism of action is unclear, given the lack of relationship between change in plasma zeaxanthin and change in macular characteristics.",
"title": "Goji berry effects on macular characteristics and plasma antioxidant levels."
},
{
"docid": "MED-4154",
"text": "Daily diet may have implications for skin ageing. However, data on the relationship between diet and the parameters of skin conditions are scarce. The present study aimed to examine the associations of biophysical properties of the skin of women with intakes of fats and antioxidant micronutrients as well as food groups as sources of these nutrients. In a cross-sectional study, we measured the hydration, surface lipids and elasticity of the skin of 716 Japanese women using non-invasive techniques. The extent of facial wrinkles in the crow's-foot area was determined by observation using the Daniell scale. Each subject's usual diet was determined with the use of a validated FFQ. After controlling for covariates including age, smoking status, BMI and lifetime sun exposure, the results showed that higher intakes of total fat, saturated fat and monounsaturated fat were significantly associated with increased skin elasticity. A higher intake of green and yellow vegetables was significantly associated with a decreased Daniell wrinkling score. Intake of saturated fat was significantly inversely associated with the Daniell wrinkling score after additional adjustment for green and yellow vegetable intake. Further studies with more accurate measurement methods are needed to investigate the role of daily diet in skin ageing.",
"title": "Association of dietary fat, vegetables and antioxidant micronutrients with skin ageing in Japanese women."
},
{
"docid": "MED-2889",
"text": "Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. Cataract extraction is the most common surgical procedure in developed countries. Lutein (L) and zeaxanthin (Z), retinal carotenoids, are the most powerful retinal anti-oxidants and absorb the harmful blue light. The depletion of L+Z induces the development of the lens opacification-cataract. Cataract reduces the retinal oxidative stress (OS), which causes a reduction of the probability to develop AMD. Oxidative Stress at the retinal level is the common pathway in the development of AMD and cataract. AMD and cataract are not two independent processes. Cataract is a self-defense reaction of the retina to reduce OS and retinal damage. Restoring the anti-oxidative capabilities of the retina by increasing intake of L+Z reduces the likelihood of AMD and cataract. Extracting the opaque lens elevates the retinal OS and increases the rate of AMD. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Cataract is a self-defence reaction to protect the retina from oxidative damage."
},
{
"docid": "MED-5083",
"text": "A predominantly plant-based diet reduces the risk for development of several chronic diseases. It is often assumed that antioxidants contribute to this protection, but results from intervention trials with single antioxidants administered as supplements quite consistently do not support any benefit. Because dietary plants contain several hundred different antioxidants, it would be useful to know the total concentration of electron-donating antioxidants (i.e., reductants) in individual items. Such data might be useful in the identification of the most beneficial dietary plants. We have assessed systematically total antioxidants in a variety of dietary plants used worldwide, including various fruits, berries, vegetables, cereals, nuts and pulses. When possible, we analyzed three or more samples of dietary plants from three different geographic regions in the world. Total antioxidants was assessed by the reduction of Fe(3+) to Fe(2+) (i.e., the FRAP assay), which occurred rapidly with all reductants with half-reaction reduction potentials above that of Fe(3+)/Fe(2+). The values, therefore, expressed the corresponding concentration of electron-donating antioxidants. Our results demonstrated that there is more than a 1000-fold difference among total antioxidants in various dietary plants. Plants that contain most antioxidants included members of several families, such as Rosaceae (dog rose, sour cherry, blackberry, strawberry, raspberry), Empetraceae (crowberry), Ericaceae (blueberry), Grossulariaceae (black currant), Juglandaceae (walnut), Asteraceae (sunflower seed), Punicaceae (pomegranate) and Zingiberaceae (ginger). In a Norwegian diet, fruits, berries and cereals contributed 43.6%, 27.1% and 11.7%, respectively, of the total intake of plant antioxidants. Vegetables contributed only 8.9%. The systematic analysis presented here will facilitate research into the nutritional role of the combined effect of antioxidants in dietary plants.",
"title": "A systematic screening of total antioxidants in dietary plants."
},
{
"docid": "MED-2885",
"text": "OBJECTIVE: This overview of ultraviolet (UV) phototoxicity considers the interaction of UVA and short-wavelength VIS light with the retina and retinal pigment epithelium. METHODS: The damage mechanisms underlying UV retinal phototoxicity are illustrated with a literature survey and presentation of experimental results. RESULTS: Depending on the wavelength and exposure duration, light interacts with tissue by three general mechanisms: thermal, mechanical, or photochemical. Although the anterior structures of the eye absorb much of the UV component of the optical radiation spectrum, a portion of the UVA band (315-400 nm) penetrates into the retina. Natural sources, such as the sun, emit energetic UV photons in relatively long durations, which typically do not result in energy confinement in the retina, and thus do not produce thermal or mechanical damage but are capable of inducing photochemical damage. Photochemical damage in the retina proceeds through Type 1 (direct reactions involving proton or electron transfers) and Type 2 (reactions involving reactive oxygen species) mechanisms. Commonly used drugs, such as certain antibiotics, nonsteroidal anti-inflammatory drugs, psychotherapeutic agents, and even herbal medicines, may act as photosensitizers that promote retinal UV damage, if they are excited by UVA or visible light and have sufficient retinal penetration. CONCLUSIONS: Although the anterior portion of the eye is the most susceptible to UV damage, the retina is at risk to the longer UV wavelengths that propagate through the ocular media. Some phototoxicity may be counteracted or reduced by dietary intake of antioxidants and protective phytonutrients.",
"title": "Ultraviolet phototoxicity to the retina."
},
{
"docid": "MED-1754",
"text": "Conspiracist ideation has been repeatedly implicated in the rejection of scientific propositions, although empirical evidence to date has been sparse. A recent study involving visitors to climate blogs found that conspiracist ideation was associated with the rejection of climate science and the rejection of other scientific propositions such as the link between lung cancer and smoking, and between HIV and AIDS (Lewandowsky et al., in press; LOG12 from here on). This article analyses the response of the climate blogosphere to the publication of LOG12. We identify and trace the hypotheses that emerged in response to LOG12 and that questioned the validity of the paper’s conclusions. Using established criteria to identify conspiracist ideation, we show that many of the hypotheses exhibited conspiratorial content and counterfactual thinking. For example, whereas hypotheses were initially narrowly focused on LOG12, some ultimately grew in scope to include actors beyond the authors of LOG12, such as university executives, a media organization, and the Australian government. The overall pattern of the blogosphere’s response to LOG12 illustrates the possible role of conspiracist ideation in the rejection of science, although alternative scholarly interpretations may be advanced in the future.",
"title": "Recursive Fury: Conspiracist Ideation in the Blogosphere in Response to Research on Conspiracist Ideation"
},
{
"docid": "MED-1749",
"text": "Pesticides associated to genetically modified foods (PAGMF), are engineered to tolerate herbicides such as glyphosate (GLYP) and gluphosinate (GLUF) or insecticides such as the bacterial toxin bacillus thuringiensis (Bt). The aim of this study was to evaluate the correlation between maternal and fetal exposure, and to determine exposure levels of GLYP and its metabolite aminomethyl phosphoric acid (AMPA), GLUF and its metabolite 3-methylphosphinicopropionic acid (3-MPPA) and Cry1Ab protein (a Bt toxin) in Eastern Townships of Quebec, Canada. Blood of thirty pregnant women (PW) and thirty-nine nonpregnant women (NPW) were studied. Serum GLYP and GLUF were detected in NPW and not detected in PW. Serum 3-MPPA and CryAb1 toxin were detected in PW, their fetuses and NPW. This is the first study to reveal the presence of circulating PAGMF in women with and without pregnancy, paving the way for a new field in reproductive toxicology including nutrition and utero-placental toxicities. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "Maternal and fetal exposure to pesticides associated to genetically modified foods in Eastern Townships of Quebec, Canada."
},
{
"docid": "MED-1748",
"text": "Our bloodstream is considered to be an environment well separated from the outside world and the digestive tract. According to the standard paradigm large macromolecules consumed with food cannot pass directly to the circulatory system. During digestion proteins and DNA are thought to be degraded into small constituents, amino acids and nucleic acids, respectively, and then absorbed by a complex active process and distributed to various parts of the body through the circulation system. Here, based on the analysis of over 1000 human samples from four independent studies, we report evidence that meal-derived DNA fragments which are large enough to carry complete genes can avoid degradation and through an unknown mechanism enter the human circulation system. In one of the blood samples the relative concentration of plant DNA is higher than the human DNA. The plant DNA concentration shows a surprisingly precise log-normal distribution in the plasma samples while non-plasma (cord blood) control sample was found to be free of plant DNA.",
"title": "Complete Genes May Pass from Food to Human Blood"
},
{
"docid": "MED-1884",
"text": "We previously evaluated the responses to dietary cholesterol in children and young adults. In this study, the effects of dietary cholesterol on plasma lipids and LDL atherogenicity were evaluated in 42 elderly subjects (29 postmenopausal women and 13 men > 60 y old). Our exclusion criteria were diabetes, heart disease, and the use of reductase inhibitors. The study followed a randomized crossover design in which subjects were assigned to consume the equivalent of 3 large eggs (EGG) daily or the same amount of a cholesterol-free, fat-free egg substitute (SUB) for a 1-mo period. After a 3-wk washout period, subjects were assigned to the alternate treatment. The concentration of plasma cholesterol after the EGG period varied among subjects. When all subjects were evaluated, there were significant increases in LDL cholesterol (LDL-C) (P < 0.05) and HDL-C (P < 0.001) for both men and women during the EGG period, resulting in no alterations in the LDL-C:HDL-C or the total cholesterol:HDL-C ratios. In addition, the LDL peak diameter was increased during the EGG period for all subjects. In contrast, the measured parameters of LDL oxidation, conjugated diene formation, and LDL lag time did not differ between the EGG and the SUB periods. We conclude from this study that dietary cholesterol provided by eggs does not increase the risk for heart disease in a healthy elderly population.",
"title": "Maintenance of the LDL cholesterol:HDL cholesterol ratio in an elderly population given a dietary cholesterol challenge."
},
{
"docid": "MED-1747",
"text": "Knowledge of the US Public Health Syphilis Study at Tuskegee is sometime cited as a principal reason for the relatively low participation rates seen among racial/ethnic minorities, particularly African Americans, in biomedical research. However, only a few studies have actually explored this possibility. We use data from a random digit dial telephone survey of 510 African-Americans and 253 Latinos, age 18 to 45 years, to investigate associations between knowledge of the USPHS Syphilis Study at Tuskegee and endorsement of HIV/AIDS conspiracy theories. All respondents were drawn from an area of low-income, predominantly race-segregated inner city households in Los Angeles. Results indicate that African Americans were significantly more likely than Latinos to endorse HIV/AIDS conspiracy theories. Further, African Americans were more aware of the USPHS Syphilis Study at Tuskegee (SST). Nevertheless, 72% of African Americans and 94% of Latinos reported that they have never heard of the Syphilis Study at Tuskegee. Further, while awareness of the Syphilis Study at Tuskegee was a significant predictor of endorsing HIV/AIDS conspiracy theories, results suggest that other factors may be more important in accounting for low biomedical and behavioral study participation rates.",
"title": "Is there a legacy of the U.S. Public Health Syphilis Study at Tuskegee in HIV/AIDS-related beliefs among heterosexual African-Americans and Latinos?"
},
{
"docid": "MED-2894",
"text": "AIM: To examine the influence of the black currant anthocyanins (BCACs) on the disease progression of open-angle glaucoma (OAG), a randomized, placebo-controlled, double-masked trial was made in 38 patients with OAG treated by antiglaucoma drops. METHODS: BCACs (50 mg/day, n = 19) or their placebos (n = 19) were orally administered once daily for a 24-month period. Systemic blood pressure, pulse rates, intraocular pressure (IOP), ocular blood circulation by laser-speckle flowgraphy, and Humphrey visual field mean deviation (MD) were measured during the 24-month period. RESULTS: As a main outcome measurement, we evaluated the difference between the groups in MD deterioration in the eye with a better MD from the trial's baseline through 24 months. A statistically significant difference was observed between the treatment groups in mean change from baseline in MD 24 months after therapy (p = 0.039, unpaired t test). Upon administration of BCACs, the ocular blood flows during the 24-month observational period increased in comparison with placebo-treated patients. However, no significant changes were observed in systemic and ocular conditions including IOP during the 24-month period. CONCLUSIONS: Our results suggest that oral administration of BCACs may be a safe and promising supplement for patients with OAG in addition to antiglaucoma medication. Copyright © 2012 S. Karger AG, Basel.",
"title": "Two-year randomized, placebo-controlled study of black currant anthocyanins on visual field in glaucoma."
},
{
"docid": "MED-2153",
"text": "Background: Increasing nut intake has been associated with reduced risk of diabetes mellitus, which is a risk factor for pancreatic cancer. Methods: We prospectively followed 75 680 women in the Nurses' Health Study, and examined the association between nut consumption and pancreatic cancer risk. Participants with a previous history of cancer were excluded. Nut consumption was assessed at baseline and updated every 2 to 4 years. Relative risks (RRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards models. Results: We documented 466 incident cases of pancreatic cancer. After adjusting for age, height, smoking, physical activity, and total energy intake, women who consumed a 28-g (1 oz) serving size of nuts ⩾2 times per week experienced a significantly lower risk of pancreatic cancer (RR, 0.65; 95% CI, 0.47–0.92; P for trend=0.007) when compared with those who largely abstained from nuts. The results did not appreciably change after further adjustment for body mass index (BMI) and history of diabetes mellitus (RR, 0.68; 95% CI, 0.48–0.95; P for trend=0.01). The inverse association persisted within strata defined by BMI, physical activity, smoking, and intakes of red meat, fruits, and vegetables. Conclusion: Frequent nut consumption is inversely associated with risk of pancreatic cancer in this large prospective cohort of women, independent of other potential risk factors for pancreatic cancer.",
"title": "Nut consumption and risk of pancreatic cancer in women"
},
{
"docid": "MED-2895",
"text": "PURPOSE: The retinal carotenoids lutein (L) and zeaxanthin (Z) that form the macular pigment (MP) may help to prevent neovascular age-related macular degeneration. The purpose of this study was to determine whether MP density in the retina could be raised by increasing dietary intake of L and Z from foods. METHODS: Macular pigment was measured psychophysically for 13 subjects. Serum concentrations of L, Z, and beta-carotene were measured by high-performance liquid chromatography. Eleven subjects modified their usual daily diets by adding 60 g of spinach (10.8 mg L, 0.3 mg Z, 5 mg beta-carotene) and ten also added 150 g of corn (0.3 mg Z, 0.4 mg L); two other subjects were given only corn. Dietary modification lasted up to 15 weeks. RESULTS: For the subjects fed spinach or spinach and corn, three types of responses to dietary modification were identified: Eight \"retinal responders\" had increases in serum L (mean, 33%; SD, 22%) and in MP density (mean, 19%; SD, 11%); two \"retinal nonresponders\" showed substantial increases in serum L (mean, 31%) but not in MP density (mean, -11%); one \"serum and retinal nonresponder\" showed no changes in serum L, Z, or beta-carotene and no change in MP density. For the two subjects given only corn, serum L changed little (+11%, -6%), but in one subject serum Z increased (70%) and MP density increased (25%). CONCLUSIONS: Increases in MP density were obtained within 4 weeks of dietary modification for most, but not all, subjects. When MP density increased with dietary modification, it remained elevated for at least several months after resuming an unmodified diet. Augmentation of MP for both experimental and clinical investigation appears to be feasible for many persons.",
"title": "Dietary modification of human macular pigment density."
},
{
"docid": "MED-1750",
"text": "The discovery of myostatin and our introduction to the “Mighty Mouse” over a decade ago spurred both basic and applied research and impacted popular culture as well. The myostatin-null genotype produces “double muscling” in mice and livestock and was recently described in a child. The field’s rapid growth is by no means surprising considering the potential benefits of enhancing muscle growth in clinical and agricultural settings. Indeed, several recent studies suggest that blocking myostatin’s inhibitory effects could improve the clinical treatment of several muscle growth disorders, whereas comparative studies suggest that these actions are at least partly conserved. Thus, neutralizing myostatin’s effects could also have agricultural significance. Extrapolating between studies that use different vertebrate models, particularly fish and mammals, is somewhat confusing because whole genome duplication events have resulted in the production and retention of up to four unique myostatin genes in some fish species. Such comparisons, however, suggest that myostatin’s actions may not be limited to skeletal muscle per se, but may additionally influence other tissues including cardiac muscle, adipocytes, and the brain. Thus, therapeutic intervention in the clinic or on the farm must consider the potential of alternative side effects that could impact these or other tissues. In addition, the presence of multiple and actively diversifying myostatin genes in most fish species provides a unique opportunity to study adaptive molecular evolution. It may also provide insight into myostatin’s nonmuscle actions as results from these and other comparative studies gain visibility in biomedical fields.",
"title": "Clinical, Agricultural, and Evolutionary Biology of Myostatin: A Comparative Review"
},
{
"docid": "MED-4689",
"text": "Background A plant-based diet protects against chronic oxidative stress-related diseases. Dietary plants contain variable chemical families and amounts of antioxidants. It has been hypothesized that plant antioxidants may contribute to the beneficial health effects of dietary plants. Our objective was to develop a comprehensive food database consisting of the total antioxidant content of typical foods as well as other dietary items such as traditional medicine plants, herbs and spices and dietary supplements. This database is intended for use in a wide range of nutritional research, from in vitro and cell and animal studies, to clinical trials and nutritional epidemiological studies. Methods We procured samples from countries worldwide and assayed the samples for their total antioxidant content using a modified version of the FRAP assay. Results and sample information (such as country of origin, product and/or brand name) were registered for each individual food sample and constitute the Antioxidant Food Table. Results The results demonstrate that there are several thousand-fold differences in antioxidant content of foods. Spices, herbs and supplements include the most antioxidant rich products in our study, some exceptionally high. Berries, fruits, nuts, chocolate, vegetables and products thereof constitute common foods and beverages with high antioxidant values. Conclusions This database is to our best knowledge the most comprehensive Antioxidant Food Database published and it shows that plant-based foods introduce significantly more antioxidants into human diet than non-plant foods. Because of the large variations observed between otherwise comparable food samples the study emphasizes the importance of using a comprehensive database combined with a detailed system for food registration in clinical and epidemiological studies. The present antioxidant database is therefore an essential research tool to further elucidate the potential health effects of phytochemical antioxidants in diet.",
"title": "The total antioxidant content of more than 3100 foods, beverages, spices, herbs and supplements used worldwide"
},
{
"docid": "MED-3001",
"text": "Over the last three decades, the concept of Western disease has become well established. Medicine has approached this group of diseases by searching for new cures but has achieved relatively little success. We argue that medicine should now accept the failure of this strategy and place a major emphasis on prevention. The key objective is to change the climate of opinion so that prevention is taken seriously by the general population. The chief activity should be a wide ranging public education campaign so as to persuade people to live a healthier lifestyle. Medicine will require restructuring in order to carry out this work. Medical education needs to be reformed so that medical students receive the necessary training. This must be done as part of an integrated approach in which government, industry and medical research all play a major role. Governments should use taxation and subsidies in areas such as food and tobacco so as to shift consumption patterns towards healthier products. Governments must also tighten laws on tobacco sales and advertising, support health education, and improve food labelling. Industry must be made far more responsive to the health needs of the population. This should be done both by public education, so as to alter demand, and by government action. Medical research should change its emphasis from studying the detailed mechanisms of disease (\"complex research\") to studying the role of lifestyle factors (\"simple research\").",
"title": "Towards a new system of health: the challenge of Western disease."
},
{
"docid": "MED-2997",
"text": "If disease patterns emerge which show that certain diseases can be related, this is a valuable pointer to a common cause. This article traces the principle of interpreting disease relationships, illustrated by several common conditions of western civilization, for which the common cause is postulated as being removal of fiber from the diet.",
"title": "The Etiological Significance of Related Diseases"
},
{
"docid": "MED-1888",
"text": "BACKGROUND Recent studies in animals have shown a mechanistic link between intestinal microbial metabolism of the choline moiety in dietary phosphatidylcholine (lecithin) and coronary artery disease through the production of a proatherosclerotic metabolite, trimethylamine-N-oxide (TMAO). We investigated the relationship among intestinal microbiota-dependent metabolism of dietary phosphatidylcholine, TMAO levels, and adverse cardiovascular events in humans. METHODS We quantified plasma and urinary levels of TMAO and plasma choline and betaine levels by means of liquid chromatography and online tandem mass spectrometry after a phosphatidylcholine challenge (ingestion of two hard-boiled eggs and deuterium [d9]-labeled phosphatidylcholine) in healthy participants before and after the suppression of intestinal microbiota with oral broad-spectrum antibiotics. We further examined the relationship between fasting plasma levels of TMAO and incident major adverse cardiovascular events (death, myocardial infarction, or stroke) during 3 years of follow-up in 4007 patients undergoing elective coronary angiography. RESULTS Time-dependent increases in levels of both TMAO and its d9 isotopologue, as well as other choline metabolites, were detected after the phosphatidylcholine challenge. Plasma levels of TMAO were markedly suppressed after the administration of antibiotics and then reappeared after withdrawal of antibiotics. Increased plasma levels of TMAO were associated with an increased risk of a major adverse cardiovascular event (hazard ratio for highest vs. lowest TMAO quartile, 2.54; 95% confidence interval, 1.96 to 3.28; P<0.001). An elevated TMAO level predicted an increased risk of major adverse cardiovascular events after adjustment for traditional risk factors (P<0.001), as well as in lower-risk subgroups. CONCLUSIONS The production of TMAO from dietary phosphatidylcholine is dependent on metabolism by the intestinal microbiota. Increased TMAO levels are associated with an increased risk of incident major adverse cardiovascular events. (Funded by the National Institutes of Health and others.)",
"title": "Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk"
},
{
"docid": "MED-1753",
"text": "Given the history of GMO conflict and debate, the GM animal future is dependent on the response of the regulatory landscape and its associated range of interest groups at national, regional and international levels. Focusing on the EU and the USA, this article examines the likely form of that multi-level response, the increased role of cultural values, the contribution of new and existing interest groups and the consequent implications for the commercialization of both green and red GM animal biotechnology. Copyright © 2012. Published by Elsevier Inc.",
"title": "The current state of GMO governance: are we ready for GM animals?"
},
{
"docid": "MED-1889",
"text": "Consumption of eggs for a long period was shown to result in hypercholesterolemia and is generally restricted for this reason. In the present study we analyzed the effect of eggs consumption for 3 weeks on lipoprotein atherogenicity. Consumption of 2 eggs per day with the meals, for 3 weeks resulted in a minor elevation in plasma glucose and urea concentrations. Plasma cholesterol concentration increased by 11% (p < 0.05) as a result of increased plasma low-density lipoprotein (LDL) cholesterol levels. Plasma triglycerides decreased by 13% (p < 0.01), but there were no significant alterations in plasma apolipoproteins A-I or B-100 concentrations. Plasma high-density lipoprotein (HDL) cholesterol decreased by 11% (p < 0.05). There was a 13% reduction, though not significant, in the cholesterol efflux from J-774 A.1 macrophages by HDL that was derived after eggs consumption in comparison to HDL that was obtained at baseline. The susceptibility of plasma [using 100 mM of 2,2' azobis 2-amidinopropane (AAPH)] as well as that of LDL (using 10 microM of copper ions) to lipid peroxidation was increased by 42% and 34%, respectively, as measured by the thiobarbituric acid reactive substance (TBARS) assay (p < 0.01). Kinetic analysis of LDL oxidation by copper ions revealed a 37% reduction in the lag time required for the initiation of LDL oxidation after 3 weeks of eggs consumption. The total plasma fatty acids concentration increased from 2.2 +/- 0.5 to 3.2 +/- 0.6 mg/ml. The plasma antioxidants, vitamin E and carotenoids were not significantly affected by eggs consumption. We conclude that eggs consumption, in addition to its hypercholesterolemic effect, increases plasma and LDL oxidizability, a phenomenon which was shown to enhance the progression of atherosclerosis. The atherogenic properties may contribute to the accelerated atherosclerosis prevalent in populations with high cholesterol intake.",
"title": "Consumption of eggs with meals increases the susceptibility of human plasma and low-density lipoprotein to lipid peroxidation."
},
{
"docid": "MED-4859",
"text": "Fresh blueberries were processed into sugar and sugar-free jams and stored for 6 months at 4 and 25 degrees C. The jams were analyzed immediately after processing and over 6 months of storage for polyphenolic content, percent polymeric color, and antioxidant capacity. Processing resulted in losses of anthocyanins, procyanidins, chlorogenic acid, and ORAC in both jam types, but flavonols were well retained. Marked losses of anthocyanins and procyanidins occurred over 6 months of storage and were accompanied by increased polymeric color values. Chlorogenic acid levels also declined during storage, but flavonols and ORAC changed little. Jams stored at 4 degrees C retained higher levels of anthocyanins, procyanidins, and ORAC and had lower polymeric color values than jams stored at 25 degrees C. Sugar-free jams retained higher levels of anthocyanins and had lower polymeric color values than sugar jams late during storage. Blueberry jams should be refrigerated to better retain polyphenolics and antioxidant capacity.",
"title": "Jam processing and storage effects on blueberry polyphenolics and antioxidant capacity."
},
{
"docid": "MED-5084",
"text": "We assessed the contribution of culinary and medicinal herbs to the total intake of dietary antioxidants. Our results demonstrate that there is more than a 1000-fold difference among antioxidant concentrations of various herbs. Of the dried culinary herbs tested, oregano, sage, peppermint, garden thyme, lemon balm, clove, allspice and cinnamon as well as the Chinese medicinal herbs Cinnamomi cortex and Scutellariae radix all contained very high concentrations of antioxidants (i.e., >75 mmol/100 g). In a normal diet, intake of herbs may therefore contribute significantly to the total intake of plant antioxidants, and be an even better source of dietary antioxidants than many other food groups such as fruits, berries, cereals and vegetables. In addition, the herbal drug, Stronger Neo-Minophagen C, a glycyrrhizin preparation used as an intravenous injection for the treatment of chronic hepatitis, boosts total antioxidant intake. It is tempting to speculate that several of the effects due to these herbs are mediated by their antioxidant activities.",
"title": "Several culinary and medicinal herbs are important sources of dietary antioxidants."
},
{
"docid": "MED-2489",
"text": "A historical view on how our agricultural systems evolved and how they are contributing to obesity and disease.",
"title": "Agricultural policies, food and public health"
},
{
"docid": "MED-2888",
"text": "Age-related macular degeneration (AMD) is a common disorder that causes irreversible loss of central vision. Increased intake of foods containing zeaxanthin may be effective in preventing AMD because the macula accumulates zeaxanthin and lutein, oxygenated carotenoids with antioxidant and blue light-absorbing properties. Lycium barbarum L. is a small red berry known as Fructus lycii and wolfberry in the West, and Kei Tze and Gou Qi Zi in Asia. Wolfberry is rich in zeaxanthin dipalmitate, and is valued in Chinese culture for being good for vision. The aim of this study, which was a single-blinded, placebo-controlled, human intervention trial of parallel design, was to provide data on how fasting plasma zeaxanthin concentration changes as a result of dietary supplementation with whole wolfberries. Fasting blood was collected from healthy, consenting subjects; fourteen subjects took 15 g/d wolfberry (estimated to contain almost 3 mg zeaxanthin) for 28 d. Repeat fasting blood was collected on day 29. Age- and sex-matched controls (n 13) took no wolfberry. Responses in the two groups were compared using the Mann-Whitney test. After supplementation, plasma zeaxanthin increased 2.5-fold: mean values on day 1 and 29 were 0.038 (sem 0.003) and 0.096 (sem 0.009) micromol/l (P<0.01), respectively, for the supplementation group; and 0.038 (sem 0.003) and 0.043 (sem 0.003) micromol/l (P>0.05), respectively, for the control group. This human supplementation trial shows that zeaxanthin in whole wolfberries is bioavailable and that intake of a modest daily amount markedly increases fasting plasma zeaxanthin levels. These new data will support further study of dietary strategies to maintain macular pigment density.",
"title": "Fasting plasma zeaxanthin response to Fructus barbarum L. (wolfberry; Kei Tze) in a food-based human supplementation trial."
},
{
"docid": "MED-1882",
"text": "BACKGROUND: Changes in conventional lipid risk factors with gemfibrozil treatment only partially explain the reductions in coronary heart disease (CHD) events experienced by men in the Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT). We examined whether measurement of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particle subclasses provides additional information relative to CHD risk reduction. METHODS AND RESULTS: This is a prospective nested case-control study of 364 men with a new CHD event (nonfatal myocardial infarction or cardiac death) during a 5.1-year (median) follow-up and 697 age-matched controls. Nuclear magnetic resonance (NMR) spectroscopy was used to quantify levels of LDL and HDL particle subclasses and mean particle sizes in plasma obtained at baseline and after 7 months of treatment with gemfibrozil or placebo. Odds ratios for a 1-SD increment of each lipoprotein variable were calculated with adjusted logistic regression models. Gemfibrozil treatment increased LDL size and lowered numbers of LDL particles (-5%) while raising numbers of HDL particles (10%) and small HDL subclass particles (21%). Concentrations of these LDL and HDL particles achieved with gemfibrozil were significant, independent predictors of new CHD events. For total LDL and HDL particles, odds ratios predicting CHD benefit were 1.28 (95% CI, 1.12 to 1.47) and 0.71 (95% CI, 0.61 to 0.81), respectively. Mean LDL and HDL particle sizes were not associated with CHD events. CONCLUSIONS: The effects of gemfibrozil on NMR-measured LDL and HDL particle subclasses, which are not reflected by conventional lipoprotein cholesterol measures, help to explain the demonstrated benefit of this therapy in patients with low HDL cholesterol.",
"title": "Low-density lipoprotein and high-density lipoprotein particle subclasses predict coronary events and are favorably changed by gemfibrozil therapy i..."
},
{
"docid": "MED-1887",
"text": "Some practitioners use advanced lipoprotein analysis with the goal of better predicting risk and individualizing lifestyle and drug therapy for cardiovascular prevention. Unfortunately, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particle number and size, other lipoprotein subfractionation, apolipoproteins B and A, and lipoprotein(a) have not yet met current standards for biomarker evaluation, and it remains to be determined whether these tests incrementally add to cardiovascular risk predicted by traditional risk factors. More importantly, it has yet to be determined whether treatment strategies guided by, or targeting, these measures improve cardiovascular outcomes. Drug therapies known to alter advanced lipoprotein analysis parameters, specifically niacin and fenofibrate, have not been shown to additionally reduce cardiovascular risk in recent randomized trials of high-risk patients treated with statin therapy. These findings suggest advanced lipoprotein analysis-guided strategies may not further reduce cardiovascular events and could lead to increased adverse effects and costs; this approach needs further research to establish its role in individualizing therapies for cardiovascular prevention. In contrast, a large body of evidence supports focusing on LDL cholesterol reduction and intensification of statin therapy to reduce cardiovascular risk. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.",
"title": "What is the role of advanced lipoprotein analysis in practice?"
},
{
"docid": "MED-2898",
"text": "PURPOSE: Age and advanced disease in the fellow eye are the two most important risk factors for age-related macular degeneration (AMD). In this study, the authors investigated the relationship between these variables and the optical density of macular pigment (MP) in a group of subjects from a northern European population. METHODS: The optical density of MP was measured psychophysically in 46 subjects ranging in age from 21 to 81 years with healthy maculae and in 9 healthy eyes known to be at high-risk of AMD because of advanced disease in the fellow eye. Each eye in the latter group was matched with a control eye on the basis of variables believed to be associated with the optical density of MP (iris color, gender, smoking habits, age, and lens density). RESULTS: There was an age-related decline in the optical density of macular pigment among volunteers with no ocular disease (right eye: r(2) = 0.29, P = 0.0006; left eye: r(2) = 0.29, P < 0.0001). Healthy eyes predisposed to AMD had significantly less MP than healthy eyes at no such risk (Wilcoxon's signed rank test: P = 0.015). CONCLUSIONS: The two most important risk factors for AMD are associated with a relative absence of MP. These findings are consistent with the hypothesis that supplemental lutein and zeaxanthin may delay, avert, or modify the course of this disease.",
"title": "Macular pigment and risk for age-related macular degeneration in subjects from a Northern European population."
},
{
"docid": "MED-2999",
"text": "Many of the commonest diseases in the economically more developed communities are characteristic of modern Western culture. Evidence is presented suggesting that they represent a failure of adaptation to the dramatic changes in diet that have been associated with the emergence of modern Western culture. Dietary changes aimed at the alleviation and prevention of these diseases are discussed and recommended.",
"title": "Western diseases and their emergence related to diet."
},
{
"docid": "MED-1890",
"text": "BACKGROUND: Several epidemiologic studies found no effect of egg consumption on the risk of coronary heart disease. It is possible that the adverse effect of eggs on LDL-cholesterol is offset by their favorable effect on HDL cholesterol. OBJECTIVE: The objective was to review the effect of dietary cholesterol on the ratio of total to HDL cholesterol. DESIGN: Studies were identified by MEDLINE and Biological s searches (from 1974 to June 1999) and by reviewing reference lists. In addition, we included data from a more recently published study. Studies were included if they had a crossover or parallel design with a control group, if the experimental diets differed only in the amount of dietary cholesterol or number of eggs and were fed for > or =14 d, and if HDL-cholesterol concentrations were reported. Of the 222 studies identified, 17 studies involving 556 subjects met these criteria. RESULTS: The addition of 100 mg dietary cholesterol/d increased the ratio of total to HDL cholesterol by 0.020 units (95% CI: 0.010, 0.030), total cholesterol concentrations by 0.056 mmol/L (2.2 mg/dL) (95% CI: 0.046, 0.065 mmol/L; 1.8, 2.5 mg/dL), and HDL-cholesterol concentrations by 0.008 mmol/L (0.3 mg/dL) (95% CI: 0.005, 0.010 mmol/L; 0.2, 0.4 mg/dL). CONCLUSIONS: Dietary cholesterol raises the ratio of total to HDL cholesterol and, therefore, adversely affects the cholesterol profile. The advice to limit cholesterol intake by reducing consumption of eggs and other cholesterol-rich foods may therefore still be valid.",
"title": "Dietary cholesterol from eggs increases the ratio of total cholesterol to high-density lipoprotein cholesterol in humans: a meta-analysis."
},
{
"docid": "MED-2765",
"text": "To prevent or delay the occurrence of chronic diseases, scientific bodies from the cardiologic and oncologic disciplines have made recommendations regarding the daily dietary intake of certain macro- and micronutrients. This study assessed the knowledge of a random population of 2,305 individuals comprising members of the public, health care workers, university graduate students, and health club attendees. Segments of this population might be expected to have a greater understanding and ability to implement these dietary recommendations. We found that over 90% of the participants were unaware of the recommendations for calcium, salt, vitamin A, and fiber, and the fiber content in a high fiber cereal. Approximately 80% of the participants were unaware of the recommendations regarding fat intake and could not calculate the fat content of a food product. Almost half of the study population took a vitamin pill daily. Of the subjects who were aware of the correct unit measurement for vitamin A (IU), almost 25% of gave a response that exceeded the recommended daily intake. A majority of this study population were unaware of the dietary recommendations regarding the prevention of cardiovascular events and cancer. Subgroups of this study population that might be expected to have more information regarding these recommendations (i.e., having higher education or being a health care professional) did not display a satisfactory level of knowledge. To further compound the problems of adhering to the recommended guidelines, the labeling of many food products is misleading. The recommendations on dietary intake and the information on food product content must be transmitted to the public in a form that allows for ready application when purchasing and consuming food.",
"title": "The value of current nutrition information."
},
{
"docid": "MED-2893",
"text": "Lutein and zeaxanthin are thought to decrease the incidence of age-related macular degeneration (AMD); however, findings have been inconsistent. We conducted a systematic literature review and meta-analysis to evaluate the relationship between dietary intake of lutein and zeaxanthin and AMD risk. Relevant studies were identified by searching five databases up to April 2010. Reference lists of articles were retrieved, and experts were contacted. Literature search, data extraction and study quality assessment were performed independently by two reviewers and results were pooled quantitatively using meta-analysis methods. The potential sources of heterogeneity and publication bias were also estimated. The search yielded six longitudinal cohort studies. The pooled relative risk (RR) for early AMD, comparing the highest with the lowest category of lutein and zeaxanthin intake, was 0·96 (95 % CI 0·78, 1·17). Dietary intake of these carotenoids was significantly related with a reduction in risk of late AMD (RR 0·74; 95 % CI 0·57, 0·97); and a statistically significant inverse association was observed between lutein and zeaxanthin intake and neovascular AMD risk (RR 0·68; 95 % CI 0·51, 0·92). The results were essentially consistent among subgroups stratified by participant characteristics. The findings of the present meta-analysis indicate that dietary lutein and zeaxanthin is not significantly associated with a reduced risk of early AMD, whereas an increase in the intake of these carotenoids may be protective against late AMD. However, additional studies are needed to confirm these relationships.",
"title": "Lutein and zeaxanthin intake and the risk of age-related macular degeneration: a systematic review and meta-analysis."
},
{
"docid": "MED-1886",
"text": "Background Nuclear magnetic resonance (NMR) spectroscopy measures the number and size of lipoprotein particles, instead of their cholesterol or triglyceride content, but its clinical utility is uncertain. Methods and Results Baseline lipoproteins were measured by NMR in 27,673 initially healthy women followed for incident cardiovascular disease (CVD, N=1,015) over 11 years. Adjusting for non-lipid risk factors, hazard ratios (HRs) and 95% confidence intervals (CIs) for top vs bottom quintile of NMR-measured lipoprotein particle concentration (particles/L) were, for low-density lipoprotein (LDLNMR) 2.51 (1.91−3.30), high-density lipoprotein (HDLNMR) 0.91 (0.75−1.12), very-low-density lipoprotein (VLDLNMR) 1.71 (1.38−2.12), and LDLNMR/HDLNMR ratio 2.25 (1.80−2.81). Similarly-adjusted results for NMR-measured lipoprotein particle size (nanometers) were, for LDLNMR size 0.64 (0.52−0.79), HDLNMR size 0.65 (0.51−0.81), and VLDLNMR size 1.37 (1.10−1.70). Hazard ratios for NMR measures were comparable but not superior to standard lipids: total cholesterol 2.08 (1.63−2.67), LDL cholesterol 1.74 (1.40−2.16), HDL cholesterol 0.52 (0.42−0.64), triglycerides 2.58 (1.95−3.41), non-HDL cholesterol 2.52 (1.95−3.25), total/HDL cholesterol ratio 2.82 (2.23−3.58); and apolipoproteins: B100 2.57 (1.98−3.33), A-1 0.63 (0.52−0.77), B100/A-1 ratio 2.79 (2.21−3.54). There was essentially no reclassification improvement with adding LDLNMR particle concentration or apolipoprotein B100 to a model that already included the total/HDL cholesterol ratio and non-lipid risk factors (net reclassification index [NRI], 0% and 1.9%, respectively), nor did the addition of either variable result in a statistically significant improvement in the c-index. Conclusions In this prospective study of healthy women, CVD risk prediction associated with lipoprotein profiles evaluated by NMR was comparable but not superior to standard lipids or apolipoproteins.",
"title": "Lipoprotein Particle Profiles by Nuclear Magnetic Resonance Compared with Standard Lipids and Apolipoproteins in Predicting Incident Cardiovascular Disease in Women"
},
{
"docid": "MED-2899",
"text": "The present study was designed to assess the relationship between iris color and macular pigment optical density. Both melanin and carotenoids (responsible for iris color and macular pigment composition, respectively) appear to protect the retina through similar mechanisms and higher concentrations may reduce the incidence of retinal degenerations. To evaluate this relationship, 95 subjects were examined and the following variables were measured: iris color; macular pigment optical density (MP); plasma concentrations of lutein and zeaxanthin and beta-carotene; dietary intake of lutein and zeaxanthin and beta-carotene; and total fat intake. Iris color was determined by self assessment and classified as blue or gray (group I), green or hazel (group II) or brown or black (group III). MP density was measured psychophysically by measuring foveal and parafoveal sensitivities to lights of 460 and 550 nm, using the method of heterochromatic flicker photometry. Plasma carotenoid concentrations were measured using reverse-phase high-performance liquid chromatography. Dietary intake was determined by a detailed food-frequency questionnaire. Despite similarities in diet and in blood concentrations of carotenoids, significant differences in macular pigment density (P < 0.02) were found for different colored irises (group I, n = 38, MP = 0.25; group II, n = 26, MP = 0.32; group III, n = 31, MP = 0.38). The covariation of iris color and MP indicates that past epidemiologic studies have not adequately determined the independent effects of either factor. The relationship of MP and iris color may be the result of one or two factors: the evolution of a shared tendency to accumulate melanin and carotenoids due to similar environmental pressures (e.g. light and oxygen); and/or MP might be depleted due to the tendency for eyes with light irises to transmit more light than eyes with dark irises, thus causing increased oxidative stress.",
"title": "Iris color and macular pigment optical density."
},
{
"docid": "MED-2488",
"text": "Cardiovascular diseases (CVD) cost Americans billions of dollars per year. High cholesterol levels, which are closely related to dietary habits, are a major contributor to CVD. In this article, we study whether changes in food prices are related to cholesterol levels and whether taxes or subsidies on particular foods would be effective in lowering cholesterol levels and, consequently, CVD costs. We find that prices of vegetables, processed foods, whole milk and whole grains are significantly associated with blood cholesterol levels. Having analyzed the costs and benefits of government interventions, we find that a subsidy of vegetables and whole grains would be an efficient way to reduce CVD expenditures. Published by Elsevier B.V.",
"title": "Food prices and blood cholesterol."
},
{
"docid": "MED-2892",
"text": "PURPOSE: The purpose of this study was to investigate the effect of bilberry on night visual acuity (VA) and night contrast sensitivity (CS). METHODS: This study utilized a double-blind, placebo-controlled, crossover design. The subjects were young males with good vision; eight received placebo and seven received active capsules for three weeks. Active capsules contained 160 mg of bilberry extract (25-percent anthocyanosides), and the placebo capsules contained only inactive ingredients. Subjects ingested one active or placebo capsule three times daily for 21 days. After the three-week treatment period, a one-month washout period was employed to allow any effect of bilberry on night vision to dissipate. In the second three-week treatment period, the eight subjects who first received placebo were given active capsules, and the seven who first received active capsules were given placebo. Night VA and night CS was tested throughout the three-month experiment. RESULTS: There was no difference in night VA during any of the measurement periods when examining the average night VA or the last night VA measurement during active and placebo treatments. In addition, there was no difference in night CS during any of the measurement periods when examining the average night CS or the last night CS measurement during active and placebo treatments. CONCLUSION: The current study failed to find an effect of bilberry on night VA or night CS for a high dose of bilberry taken for a significant duration. Hence, the current study casts doubt on the proposition that bilberry supplementation, in the forms currently available and in the doses recommended, is an effective treatment for the improvement of night vision in this population.",
"title": "The effect of bilberry nutritional supplementation on night visual acuity and contrast sensitivity."
},
{
"docid": "MED-1751",
"text": "There are many ways to categorise conspiracy theories. In the present study, we examined individual and demographic predictors of beliefs in commercial conspiracy theories among a British sample of over 300 women and men. Results showed many people were cynical and sceptical with regard to advertising tricks, as well as the tactics of organisations like banks and alcohol, drug and tobacco companies. Beliefs sorted into four identifiable clusters, labelled sneakiness, manipulative, change-the-rules and suppression/prevention. The high alpha for the overall scale suggested general beliefs in commercial conspiracy. Regressions suggested that those people who were less religious, more left-wing, more pessimistic, less (self-defined as) wealthy, less Neurotic and less Open-to-Experience believed there was more commercial conspiracy. Overall the individual difference variables explained relatively little of the variance in these beliefs. The implications of these findings for the literature on conspiracy theories are discussed. Limitations of the study are also discussed.",
"title": "Commercial conspiracy theories: a pilot study"
},
{
"docid": "MED-1885",
"text": "PURPOSE OF REVIEW: The perceived notion that dietary cholesterol is associated with increased risk for coronary heart disease (CHD) has led to dietary recommendations of no more than 300 mg/day for healthy populations in the USA. This study will review the recent evidence that challenges the current dietary restrictions regarding cholesterol while it presents some beneficial effects of eggs (an icon for dietary cholesterol) in healthy individuals. RECENT FINDINGS: The European countries, Australia, Canada, New Zealand, Korea and India among others do not have an upper limit for cholesterol intake in their dietary guidelines. Further, existing epidemiological data have clearly demonstrated that dietary cholesterol is not correlated with increased risk for CHD. Although numerous clinical studies have shown that dietary cholesterol challenges may increase plasma LDL cholesterol in certain individuals, who are more sensitive to dietary cholesterol (about one-quarter of the population), HDL cholesterol also rises resulting in the maintenance of the LDL/HDL cholesterol ratio, a key marker of CHD risk. SUMMARY: The lines of evidence coming from current epidemiological studies and from clinical interventions utilizing different types of cholesterol challenges support the notion that the recommendations limiting dietary cholesterol should be reconsidered.",
"title": "Rethinking dietary cholesterol."
},
{
"docid": "MED-2882",
"text": "Retinal pigment epithelium (RPE) cells are vital for retinal health. However, they are susceptible to injury with ageing and exposure to excessive light, including UV (100-380 nm) and visible (380-760 nm) radiation. To evaluate the protective effect of blueberry anthocyanins on RPE cells, in vitro cell models of replicative senescent and light-induced damage were established in the present study. After purification and fractionation, blueberry anthocyanin extracts (BAE) were yielded with total anthocyanin contents of 31·0 (SD 0·5) % and were used in this study. Replicative senescence of RPE cells was induced by repeatedly passaging cells from the fourth passage to the tenth. From the fifth passage, cultured RPE cells began to enter a replicative senescence, exhibiting reduced cell proliferation along with an increase in the number of β-galactosidase-positive cells. RPE cells maintained high cell viability (P < 0·01) and a low (P < 0·01) percentage of β-galactosidase-positive cells when treated with 0·1 μg/ml BAE. In contrast, after exposure to 2500 (SD 500) lx light (420-800 nm) for 12 h, RPE cells in the positive control (light exposure, no BAE treatment) exhibited premature senescence, low (P < 0·01) cell viability and increased (P < 0·01) vascular endothelial growth factor (VEGF) release compared with negative control cells, which were not subjected to light irradiation and BAE exposure. Correspondingly, BAE is beneficial to RPE cells by protecting these cells against light-induced damage through the suppression of ageing and apoptosis as well as the down-regulation of the over-expressed VEGF to normal level. These results demonstrate that BAE is efficacious against senescence and light-induced damage of RPE cells.",
"title": "Blueberry anthocyanins: protection against ageing and light-induced damage in retinal pigment epithelial cells."
},
{
"docid": "MED-4646",
"text": "Objective We examined the association between adolescent fiber intake and proliferative BBD, a marker of increased breast cancer risk, in the Nurses’ Health Study II. Methods Among 29,480 women who completed a high school diet questionnaire in 1998, 682 proliferative BBD cases were identified and confirmed by centralized pathology review between 1991 and 2001. Multivariate-adjusted Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results Women in the highest quintile of adolescent fiber intake had a 25% lower risk of proliferative BBD (multivariate HR (95% CI): 0.75 (0.59, 0.96), p-trend = 0.01) than women in the lowest quintile. High school intake of nuts and apples was also related to significantly reduced BBD risk. Women consuming ≥2 servings of nuts/week had a 36% lower risk (multivariate HR (95% CI): 0.64 (0.48, 0.85), p-trend < 0.01) than women consuming <1 serving/month. Results were essentially the same when the analysis was restricted to prospective cases (n = 142) diagnosed after return of the high school diet questionnaire. Conclusions These findings support the hypothesis that dietary intake of fiber and nuts during adolescence influence subsequent risk of breast disease and may suggest a viable means for breast cancer prevention.",
"title": "Intake of Fiber and Nuts during Adolescence and Incidence of Proliferative Benign Breast Disease"
}
] |
[
{
"docid": "MED-5012",
"text": "This study investigated the effect of coconut flakes on serum cholesterol levels of humans with moderately raised serum cholesterol in 21 subjects. The serum total cholesterol of subjects differed and ranged from 259 to 283 mg/dL. The study was conducted in a double-blind randomized crossover design on a 14-week period, consisting of four 2-week experimental periods, with each experimental period separated by a 2-week washout period. The test foods were as follows: corn flakes as the control food, oat bran flakes as the reference food, and corn flakes with 15% and 25% dietary fiber from coconut flakes (made from coconut flour production). Results showed a significant percent reduction in serum total and low-density lipoprotein (LDL) cholesterol (in mg/dL) for all test foods, except for corn flakes, as follows: oat bran flakes, 8.4 +/- 1.4 and 8.8 +/- 6.0, respectively; 15% coconut flakes, 6.9 +/- 1.1 and 11.0 +/- 4.0, respectively; and 25% coconut flakes, 10.8 +/- 1.3 and 9.2 +/- 5.4, respectively. Serum triglycerides were significantly reduced for all test foods: corn flakes, 14.5 +/- 6.3%; oat bran flakes, 22.7 +/- 2.9%; 15% coconut flakes, 19.3 +/- 5.7%; and 25% coconut flakes, 21.8 +/- 6.0%. Only 60% of the subjects were considered for serum triglycerides reduction (serum triglycerides >170 mg/dL). In conclusion, both 15% and 25% coconut flakes reduced serum total and LDL cholesterol and serum triglycerides of humans with moderately raised serum cholesterol levels. Coconut flour is a good source of both soluble and insoluble dietary fiber, and both types of fiber may have significant role in the reduction of the above lipid biomarker. To our knowledge, this is the first study conducted to show a relationship between dietary fiber from a coconut by-product and a lipid biomarker. Results from this study serves as a good basis in the development of coconut flakes/flour as a functional food, justifying the increased production of coconut and coconut by-products.",
"title": "The cholesterol-lowering effect of coconut flakes in humans with moderately raised serum cholesterol."
},
{
"docid": "MED-5167",
"text": "OBJECTIVES: The phytoestrogen (plant estrogen) genistein, present in soy products, is of interest because in utero exposure to genistein can cause hypospadias in our mouse model and maternal consumption of soy is prevalent in human populations. Another compound of interest is the fungicide vinclozolin, which also causes hypospadias in the mouse and rat and can occur concurrently with genistein in the diet as a residue on exposed foods. A study in the United Kingdom found no relationship between a maternal organic vegetarian diet and hypospadias frequency, but women who consumed nonorganic vegetarian diets had a greater percentage of sons with hypospadias. Because nonorganic diets can include residues of pesticides such as vinclozolin, we sought to assess the interaction of realistic daily exposures to genistein and vinclozolin and their effects on the incidence of hypospadias. METHODS: Pregnant mice were fed a soy-free diet and orally gavaged from gestational days 13 to 17 with 0.17 mg/kg/day of genistein, 10 mg/kg/day of vinclozolin, or genistein and vinclozolin together at the same doses, all in 100 microL of corn oil. The controls received the corn oil vehicle. The male fetuses were examined at gestational day 19 for hypospadias, both macroscopically and histologically. RESULTS: We identified no hypospadias in the corn oil group. The incidence of hypospadias was 25% with genistein alone, 42% with vinclozolin alone, and 41% with genistein and vinclozolin together. CONCLUSIONS: These findings support the idea that exposure to these compounds during gestation could contribute to the development of hypospadias.",
"title": "Endocrine disruptors and hypospadias: role of genistein and the fungicide vinclozolin."
},
{
"docid": "MED-1710",
"text": "Sugar intake in the United States has increased by >40 fold since the American Revolution. The health concerns that have been raised about the amounts of sugar that are in the current diet, primarily as beverages, are the subject of this review. Just less than 50% of the added sugars (sugar and high-fructose corn syrup) are found in soft drinks and fruit drinks. The intake of soft drinks has increased 5-fold between 1950 and 2000. Most meta-analyses have shown that the risk of obesity, diabetes, cardiovascular disease, and metabolic syndrome are related to consumption of beverages sweetened with sugar or high-fructose corn syrup. Calorically sweetened beverage intake has also been related to the risk of nonalcoholic fatty liver disease, and, in men, gout. Calorically sweetened beverages contribute to obesity through their caloric load, and the intake of beverages does not produce a corresponding reduction in the intake of other food, suggesting that beverage calories are “add-on” calories. The increase in plasma triglyceride concentrations by sugar-sweetened beverages can be attributed to fructose rather than glucose in sugar. Several randomized trials of sugar-containing soft drinks versus low-calorie or calorie-free beverages show that either sugar, 50% of which is fructose, or fructose alone increases triglycerides, body weight, visceral adipose tissue, muscle fat, and liver fat. Fructose is metabolized primarily in the liver. When it is taken up by the liver, ATP decreases rapidly as the phosphate is transferred to fructose in a form that makes it easy to convert to lipid precursors. Fructose intake enhances lipogenesis and the production of uric acid. By worsening blood lipids, contributing to obesity, diabetes, fatty liver, and gout, fructose in the amounts currently consumed is hazardous to the health of some people.",
"title": "Energy and Fructose From Beverages Sweetened With Sugar or High-Fructose Corn Syrup Pose a Health Risk for Some People"
},
{
"docid": "MED-2054",
"text": "OBJECTIVE: To determine the prevalence of constipation in children <or=2 years, describe the symptoms of constipation, and review how often specific interventions were effective. STUDY DESIGN: Retrospective chart review. RESULTS: Of 4,157 children <2 years of age, 185 children had constipation. The prevalence rate for constipation in the first year of life was 2.9%, and in the second year of life, the rate was 10.1%. Functional constipation was the cause in 97% of the children. Boys and girls were affected with equal frequency. Constipation was caused by an underlying organic disease in 1.6% of cases, and 97% of the children had functional constipation. Dietary changes and corn syrup were the initial treatment suggestions for 116 children; 93% of these children underwent follow-up examinations, and the constipation resolved in 25% of the children. Of 100 children treated with milk of magnesia or polyethylene glycol 3350 without electrolytes, 93 children underwent follow-up examinations, and the constipation was resolved with treatment in 92% of the children. CONCLUSIONS: Dietary changes, corn syrup, or both resolved constipation in 25% of children, and laxatives resolved constipation in 92% of children. Both milk of magnesia and polyethylene glycol were efficient and safe in infants and toddlers.",
"title": "Prevalence, symptoms and outcome of constipation in infants and toddlers."
},
{
"docid": "MED-3143",
"text": "BACKGROUND: Olestra is a nonabsorbable, energy-free fat substitute. Because it is not absorbed, it may cause digestive symptoms when consumed in large amounts. OBJECTIVE: To compare the frequency and impact of gastrointestinal symptoms in adults and children who freely consume snacks containing olestra or regular snacks in the home. DESIGN: 6-week, double-blind, randomized, parallel, placebo-controlled trial. SETTING: General community. PARTICIPANTS: 3181 volunteers 2 to 89 years of age. INTERVENTION: Households received identical packages labeled as containing olestra corn or potato chips. These packages contained either olestra or regular chips (control). MEASUREMENT: Gastrointestinal symptoms and their impact on daily activities were reported in a daily record. RESULTS: At least one gastrointestinal symptom was reported by 619 of 1620 (38.2%) persons in the olestra group and 576 of 1561 (36.9%) controls (difference, 1.3 percentage points [95% CI, -3.6 to 6.2 percentage points]; P = 0.60). In general, the groups did not differ significantly in the proportion of participants who reported individual gastrointestinal symptoms; however, more controls reported nausea (8.4% compared with 5.7%; difference, -2.7 percentage points [CI, -4.9 to -0.4 percentage points]; P = 0.02). The only difference between groups for the mean numbers of days on which symptoms were reported was that participants in the olestra group had 1 more symptom-day of more frequent bowel movements than did controls (3.7 symptom-days compared with 2.8 symptom days; difference, 0.9 symptom-days [CI, 0.1 to 1.8 symptom-days]; P = 0.04). The groups did not differ in the impact of symptoms on daily activities. CONCLUSIONS: Clinically meaningful or bothersome gastrointestinal effects are not associated with unregulated consumption of olestra corn and potato chips in the home.",
"title": "Gastrointestinal symptoms in 3181 volunteers ingesting snack foods containing olestra or triglycerides. A 6-week randomized, placebo-controlled trial."
},
{
"docid": "MED-5056",
"text": "BACKGROUND: Oxidative damage is implicated in the etiology of cancer, cardiovascular disease, and other degenerative disorders. Recent nutritional research has focused on the antioxidant potential of foods, while current dietary recommendations are to increase the intake of antioxidant-rich foods rather than supplement specific nutrients. Many alternatives to refined sugar are available, including raw cane sugar, plant saps/syrups (eg, maple syrup, agave nectar), molasses, honey, and fruit sugars (eg, date sugar). Unrefined sweeteners were hypothesized to contain higher levels of antioxidants, similar to the contrast between whole and refined grain products. OBJECTIVE: To compare the total antioxidant content of natural sweeteners as alternatives to refined sugar. DESIGN: The ferric-reducing ability of plasma (FRAP) assay was used to estimate total antioxidant capacity. Major brands of 12 types of sweeteners as well as refined white sugar and corn syrup were sampled from retail outlets in the United States. RESULTS: Substantial differences in total antioxidant content of different sweeteners were found. Refined sugar, corn syrup, and agave nectar contained minimal antioxidant activity (<0.01 mmol FRAP/100 g); raw cane sugar had a higher FRAP (0.1 mmol/100 g). Dark and blackstrap molasses had the highest FRAP (4.6 to 4.9 mmol/100 g), while maple syrup, brown sugar, and honey showed intermediate antioxidant capacity (0.2 to 0.7 mmol FRAP/100 g). Based on an average intake of 130 g/day refined sugars and the antioxidant activity measured in typical diets, substituting alternative sweeteners could increase antioxidant intake an average of 2.6 mmol/day, similar to the amount found in a serving of berries or nuts. CONCLUSION: Many readily available alternatives to refined sugar offer the potential benefit of antioxidant activity.",
"title": "Total antioxidant content of alternatives to refined sugar."
},
{
"docid": "MED-717",
"text": "OBJECTIVE: Fructose intake has increased considerably in the United States, primarily as a result of increased consumption of high-fructose corn syrup, fruits and juices, and crystalline fructose. The purpose was to determine how often fructose, in amounts commonly consumed, would result in malabsorption and/or symptoms in healthy persons. DESIGN: Fructose absorption was measured using 3-hour breath hydrogen tests and symptom scores were used to rate subjective responses for gas, borborygmus, abdominal pain, and loose stools. SUBJECTS/SETTING: The study included 15 normal, free-living volunteers from a medical center community and was performed in a gastrointestinal specialty clinic. INTERVENTION: Subjects consumed 25- and 50-g doses of crystalline fructose with water after an overnight fast on separate test days. MAIN OUTCOME MEASURES: Mean peak breath hydrogen, time of peak, area under the curve (AUC) for breath hydrogen and gastrointestinal symptoms were measured during a 3-hour period after subjects consumed both 25- and 50-g doses of fructose. STATISTICAL ANALYSES: Differences in mean breath hydrogen, AUC, and symptom scores between doses were analyzed using paired t tests. Correlations among peak breath hydrogen, AUC, and symptoms were also evaluated. RESULTS: More than half of the 15 adults tested showed evidence of fructose malabsorption after 25 g fructose and greater than two thirds showed malabsorption after 50 g fructose. AUC, representing overall breath hydrogen response, was significantly greater after the 50-g dose. Overall symptom scores were significantly greater than baseline after each dose, but scores were only marginally greater after 50 g than 25 g. Peak hydrogen levels and AUC were highly correlated, but neither was significantly related to symptoms. CONCLUSIONS: Fructose, in amounts commonly consumed, may result in mild gastrointestinal distress in normal people. Additional study is warranted to evaluate the response to fructose-glucose mixtures (as in high-fructose corn syrup) and fructose taken with food in both normal people and those with gastrointestinal dysfunction. Because breath hydrogen peaks occurred at 90 to 114 minutes and were highly correlated with 180-minute breath hydrogen AUC, the use of peak hydrogen measures may be considered to shorten the duration of the exam.",
"title": "Fructose intake at current levels in the United States may cause gastrointestinal distress in normal adults."
},
{
"docid": "MED-3382",
"text": "Artificial food colors (AFCs) have not been established as the main cause of attention-deficit hyperactivity disorder (ADHD), but accumulated evidence suggests that a subgroup shows significant symptom improvement when consuming an AFC-free diet and reacts with ADHD-type symptoms on challenge with AFCs. Of children with suspected sensitivities, 65% to 89% reacted when challenged with at least 100 mg of AFC. Oligoantigenic diet studies suggested that some children in addition to being sensitive to AFCs are also sensitive to common nonsalicylate foods (milk, chocolate, soy, eggs, wheat, corn, legumes) as well as salicylate-containing grapes, tomatoes, and orange. Some studies found \"cosensitivity\" to be more the rule than the exception. Recently, 2 large studies demonstrated behavioral sensitivity to AFCs and benzoate in children both with and without ADHD. A trial elimination diet is appropriate for children who have not responded satisfactorily to conventional treatment or whose parents wish to pursue a dietary investigation.",
"title": "Dietary sensitivities and ADHD symptoms: thirty-five years of research."
},
{
"docid": "MED-1672",
"text": "The intake of added sugars, such as from table sugar (sucrose) and high-fructose corn syrup has increased dramatically in the last hundred years and correlates closely with the rise in obesity, metabolic syndrome, and diabetes. Fructose is a major component of added sugars and is distinct from other sugars in its ability to cause intracellular ATP depletion, nucleotide turnover, and the generation of uric acid. In this article, we revisit the hypothesis that it is this unique aspect of fructose metabolism that accounts for why fructose intake increases the risk for metabolic syndrome. Recent studies show that fructose-induced uric acid generation causes mitochondrial oxidative stress that stimulates fat accumulation independent of excessive caloric intake. These studies challenge the long-standing dogma that “a calorie is just a calorie” and suggest that the metabolic effects of food may matter as much as its energy content. The discovery that fructose-mediated generation of uric acid may have a causal role in diabetes and obesity provides new insights into pathogenesis and therapies for this important disease.",
"title": "Sugar, Uric Acid, and the Etiology of Diabetes and Obesity"
},
{
"docid": "MED-3494",
"text": "Americans are becoming more health conscious in their food choices and many are interested in reducing dietary fat intake. Fat replacers can affect meat flavor both by adding flavors of their own, by reducing the original aroma-generating substrate (fat) and by altering release of aroma compounds. When fat is removed from meat, water is generally added to replace it. Water-binding compounds can be added to prevent the added water from cooking out or evaporating and to prevent patty shrinkage. Fat replacers are generally classified by their composition: protein-based replacers including whey, soy and collagen, lipid-based substances such as soy lecithin which function as emulsifiers maintaining the fat that is retained distributed in the product, and carbohydrate-based substances including flours (wheat, soy, oat), starches (potato, modified corn starch, tapioca) and gums (carrageenan, xanthin). Duplication of the characteristics contributed by fat often requires a combination of replacers to address juiciness and texture (firmness) without negatively impacting flavor. Published by Elsevier Ltd.",
"title": "Reducing the fat content in ground beef without sacrificing quality: a review."
},
{
"docid": "MED-4446",
"text": "Twenty-four plant lignans were analyzed by high-performance liquid chromatography-tandem mass spectrometry in bran extracts of 16 cereal species, in four nut species, and in two oilseed species (sesame seeds and linseeds). Eighteen of these were lignans previously unidentified in these species, and of these, 16 were identified in the analyzed samples. Four different extraction methods were applied as follows: alkaline extraction, mild acid extraction, a combination of alkaline and mild acid extraction, or accelerated solvent extraction. The extraction method was of great importance for the lignan yield. 7-Hydroxymatairesinol, which has not previously been detected in cereals because of destructive extraction methods, was the dominant lignan in wheat, triticale, oat, barley, millet, corn bran, and amaranth whole grain. Syringaresinol was the other dominant cereal lignan. Wheat and rye bran had the highest lignan content of all cereals; however, linseeds and sesame seeds were by far the most lignan-rich of the studied species.",
"title": "Quantification of a broad spectrum of lignans in cereals, oilseeds, and nuts."
},
{
"docid": "MED-906",
"text": "Annatto dye is an orange-yellow food coloring extracted from the seeds of the tree Bixa orellana. It is commonly used in cheeses, snack foods, beverages, and cereals. Previously reported adverse reactions associated with annatto dye have included urticaria and angioedema. We present a patient who developed urticaria, angioedema, and severe hypotension within 20 minutes following ingestion of milk and Fiber One cereal, which contained annatto dye. Subsequent skin tests to milk, wheat, and corn were negative. The patient had a strong positive skin test to annatto dye, while controls had no response. The nondialyzable fraction of annatto dye on SDS-PAGE demonstrated two protein staining bands in the range of 50 kD. Immunoblotting demonstrated patient IgE-specific for one of these bands, while controls showed no binding. Annatto dye may contain contaminating or residual seed proteins to which our patient developed IgE hypersensitivity. Annatto dye is a potential rare cause of anaphylaxis.",
"title": "Anaphylaxis to annatto dye: a case report."
},
{
"docid": "MED-5263",
"text": "High postprandial serum lipid concentrations are associated with increased oxidative stress which, in turn, increases the risk of atherosclerosis. Epidemiological studies correlate lower incidence of cardiovascular disease with adherence to the Mediterranean diet. The aim of this study was to evaluate changes in inflammatory (TXB(2) and LTB(4)) and oxidative stress markers (urinary hydrogen peroxide levels and serum antioxidant capacity), in addition to classic lipid parameters, after a fat-rich meal administered to 12 normolipemic, healthy subjects. Following a Latin square design, subjects were divided into three groups, each one receiving a different kind of oil (extra virgin olive oil; EVOO, olive oil; OO or corn oil; CO, together with 150g of potatoes), with 2-week washout periods between treatments. Blood samples were drawn at baseline and after 1, 2, and 6h after the meal. A significant decrease in inflammatory markers, namely TXB(2) and LTB(4), after 2 and 6h after EVOO (but not OO or CO) consumption and a concomitant increase of serum antioxidant capacity were recorded. These data reinforce the notion that the Mediterranean diet reduces the incidence of coronary heart disease partially due to the protective role of its phenolic components, including those of extra virgin olive oil.",
"title": "Postprandial anti-inflammatory and antioxidant effects of extra virgin olive oil."
},
{
"docid": "MED-1837",
"text": "Because manganese (Mn) is potentially toxic, and because dietary fat type may affect Mn absorption, the objectives of the current study were to determine whether diets containing very low or very high amounts of Mn and enriched in either saturated or unsaturated fats affected measures of neuropsychological and basic metabolic function. Healthy young women were fed for 8 wk each, in a crossover design, diets that provided 0.8 or 20 mg of Mn/d. One half of the subjects received 15% of energy as cocoa butter, and one half received 15% of energy as corn oil. A meal containing (54)Mn was fed after 4 wk, and subjects underwent whole-body counting for the next 21 d. Blood draws and neuropsychological tests were administered at regular intervals during the dietary periods. When subjects consumed the diets low in Mn, compared with the high Mn diets, they absorbed a significantly higher percentage of (54)Mn, but had a significantly longer biological half-life of the absorbed (54)Mn. Manganese intake did not affect any neurological measures and only minimally affected psychologic variables. These data show that efficient mechanisms operate to maintain Mn homeostasis over the range of intakes that may be encountered in a mixed Western diet. Thus, dietary intakes of Mn from 0.8 to 20 mg for 8 wk likely do not result in Mn deficiency or toxicity signs in healthy adults.",
"title": "Dietary manganese intake and type of lipid do not affect clinical or neuropsychological measures in healthy young women."
},
{
"docid": "MED-3821",
"text": "Reducing the concentration of polyamines (spermine, spermidine, and putrescine) in the body pool may slow the cancer process. Because dietary spermine, spermidine, and putrescine contribute to the body pool of polyamines, quantifying them in the diet is important. Limited information about polyamine content of food is available, especially for diets in the United States. This brief report describes the development of a polyamine database linked to the Fred Hutchinson Cancer Center food frequency questionnaire (FFQ). Values for spermine, spermidine, and putrescine were calculated and reported per serving size (nmol/serving). Of the foods from the database that were evaluated, fresh and frozen corn contain the highest levels of putrescine (560,000 nmol/serving and 902,880 nmol/serving) and spermidine (137,682 nmol/serving and 221,111 nmol/serving), and green pea soup contains the highest concentration of spermine (36,988 nmol/serving). The polyamine database and FFQ were tested with a convenience sample (n=165). Average daily polyamine intakes from the sample were: 159,133 nmol/day putrescine, 54,697 nmol/day spermidine, and 35,698 nmol/day spermine. Orange and grapefruit juices contributed the greatest amount of putrescine (44,441 nmol/day) to the diet. Green peas contributed the greatest amount of spermidine (3,283 nmol/day) and ground meat contributed the greatest amount of spermine (2,186 nmol/day). Development of this database linked to an FFQ provides a means of estimating polyamine intake and contributes to investigations relating polyamines to cancer.",
"title": "Development of a Polyamine Database for Assessing Dietary Intake"
},
{
"docid": "MED-5034",
"text": "The association between cured and broiled meat consumption by the mother during pregnancy and by the child was examined in relation to childhood cancer. Five meat groups (ham, bacon, or sausage; hot dogs; hamburgers; bologna, pastrami, corned beef, salami, or lunch meat; charcoal broiled foods) were assessed. Exposures among 234 cancer cases (including 56 acute lymphocytic leukemia [ALL], 45 brain tumor) and 206 controls selected by random-digit dialing in the Denver, Colorado (United States) standard metropolitan statistical area were compared, with adjustment for confounders. Maternal hot-dog consumption of one or more times per week was associated with childhood brain tumors (odds ratio [OR] = 2.3, 95 percent confidence interval [CI] = 1.0-5.4). Among children, eating hamburgers one or more times per week was associated with risk of ALL (OR = 2.0, CI = 0.9-4.6) and eating hot dogs one or more times per week was associated with brain tumors (OR = 2.1, CI = 0.7-6.1). Among children, the combination of no vitamins and eating meats was associated more strongly with both ALL and brain cancer than either no vitamins or meat consumption alone, producing ORs of two to seven. The results linking hot dogs and brain tumors (replicating an earlier study) and the apparent synergism between no vitamins and meat consumption suggest a possible adverse effect of dietary nitrites and nitrosamines.",
"title": "Cured and broiled meat consumption in relation to childhood cancer: Denver, Colorado (United States)"
},
{
"docid": "MED-2490",
"text": "Background: Rice can be a major source of inorganic arsenic (Asi) for many sub-populations. Rice products are also used as ingredients in prepared foods, some of which may not be obviously rice based. Organic brown rice syrup (OBRS) is used as a sweetener in organic food products as an alternative to high-fructose corn syrup. We hypothesized that OBRS introduces As into these products. Objective: We determined the concentration and speciation of As in commercially available brown rice syrups and in products containing OBRS, including toddler formula, cereal/energy bars, and high-energy foods used by endurance athletes. Methods: We used inductively coupled plasma mass spectrometry (ICP-MS) and ion chromatography coupled to ICP-MS to determine total As (Astotal) concentrations and As speciation in products purchased via the Internet or in stores in the Hanover, New Hampshire, area. Discussion: We found that OBRS can contain high concentrations of Asi and dimethyl-arsenate (DMA). An “organic” toddler milk formula containing OBRS as the primary ingredient had Astotal concentrations up to six times the U.S. Environmental Protection Agency safe drinking water limit. Cereal bars and high-energy foods containing OBRS also had higher As concentrations than equivalent products that did not contain OBRS. Asi was the main As species in most food products tested in this study. Conclusions: There are currently no U.S. regulations applicable to As in food, but our findings suggest that the OBRS products we evaluated may introduce significant concentrations of Asi into an individual’s diet. Thus, we conclude that there is an urgent need for regulatory limits on As in food.",
"title": "Arsenic, Organic Foods, and Brown Rice Syrup"
},
{
"docid": "MED-3734",
"text": "Cranberry products and especially cranberry juice (CJ) have been consumed for health reasons primarily due to their effect on urinary tract infections. We investigated the quantity of both free and total (after hydrolysis) phenolic antioxidants in cranberry products using the Folin assay. The order of amount of total polyphenols in cranberry foods on a fresh weight basis was as follows: dried > frozen > sauce > jellied sauce. On a serving size basis for all cranberry products, the order was as follows: frozen > 100% juice > dried > 27% juice > sauce > jellied sauce. High fructose corn syrup (HFCS) is a major source of sugar consumption in the U.S. and contains both glucose and fructose, potential mediators of oxidative stress. We investigated the effect of the consumption of HFCS and ascorbate with CJ antioxidants or without CJ (control) given to 10 normal individuals after an overnight fast. Plasma antioxidant capacity, glucose, triglycerides, and ascorbate were measured 6 times over 7 h after the consumption of a single 240 mL serving of the two different beverages. The control HFCS caused a slight decrease in plasma antioxidant capacity at all time points and thus an oxidative stress in spite of the presence of ascorbate. CJ produced an increase in plasma antioxidant capacity that was significantly greater than control HFCS at all time points. Postprandial triglycerides, due to fructose in the beverages, were mainly responsible for the oxidative stress and were significantly correlated with the oxidative stress as measured by the antioxidant capacity. Cranberries are an excellent source of high quality antioxidants and should be examined in human supplementation studies.",
"title": "Cranberries and cranberry products: powerful in vitro, ex vivo, and in vivo sources of antioxidants."
},
{
"docid": "MED-5057",
"text": "High fructose corn syrup (HFCS) has become an increasingly common food ingredient in the last 40 years. However, there is concern that HFCS consumption increases the risk for obesity and other adverse health outcomes compared to other caloric sweeteners. The most commonly used types of HFCS (HFCS-42 and HFCS-55) are similar in composition to sucrose (table sugar), consisting of roughly equal amounts of fructose and glucose. The primary difference is that these monosaccharides exist free in solution in HFCS, but in disaccharide form in sucrose. The disaccharide sucrose is easily cleaved in the small intestine, so free fructose and glucose are absorbed from both sucrose and HFCS. The advantage to food manufacturers is that the free monosaccharides in HFCS provide better flavor enhancement, stability, freshness, texture, color, pourability, and consistency in foods in comparison to sucrose. Because the composition of HFCS and sucrose is so similar, particularly on absorption by the body, it appears unlikely that HFCS contributes more to obesity or other conditions than sucrose does. Nevertheless, few studies have evaluated the potentially differential effect of various sweeteners, particularly as they relate to health conditions such as obesity, which develop over relatively long periods of time. Improved nutrient databases are needed to analyze food consumption in epidemiologic studies, as are more strongly designed experimental studies, including those on the mechanism of action and relationship between fructose dose and response. At the present time, there is insufficient evidence to ban or otherwise restrict use of HFCS or other fructose-containing sweeteners in the food supply or to require the use of warning labels on products containing HFCS. Nevertheless, dietary advice to limit consumption of all added caloric sweeteners, including HFCS, is warranted.",
"title": "The effects of high fructose syrup."
},
{
"docid": "MED-5085",
"text": "In this study, the adhesion factors examined were time between frying and coating, surface oil content, chip temperature, oil composition, NaCl size, NaCl shape, and electrostatic coating. Three different surface oil content potato chips, high, low, and no, were produced. Oils used were soybean, olive, corn, peanut, and coconut. After frying, chips were coated immediately, after 1 d, and after 1 mo. NaCl crystals of 5 different particle sizes (24.7, 123, 259, 291, and 388 microm) were coated both electrostatically and nonelectrostatically. Adhesion of cubic, dendritic, and flake crystals was examined. Chips were coated at different temperatures. Chips with high surface oil had the highest adhesion of salt, making surface oil content the most important factor. Decreasing chip temperature decreased surface oil and adhesion. Increasing time between frying and coating reduced adhesion for low surface oil chips, but did not affect high and no surface oil chips. Changing oil composition did not affect adhesion. Increasing salt size decreased adhesion. Salt size had a greater effect on chips with lower surface oil content. When there were significant differences, cubic crystals gave the best adhesion followed by flake crystals then dendritic crystals. For high and low surface oil chips, electrostatic coating did not change adhesion of small size crystals but decreased adhesion of large salts. For no surface oil content chips, electrostatic coating improved adhesion for small salt sizes but did not affect adhesion of large crystals.",
"title": "Factors dominating adhesion of NaCl onto potato chips."
},
{
"docid": "MED-5164",
"text": "Exogenous dietary putrescine (1,4-diaminobutane) can increase growth rates of neonatal animals, including calves, chicks, and piglets, under nutritional stress. Turkey poults often have a high mortality rate and this may be due to poor initial feeding behavior and inadequate development of the intestinal tract. We conducted an experiment to determine the effect of dietary putrescine supplementation on growth performance and the role of dietary putrescine in prevention and recovery from a coccidial challenge. A total of 160 1-d-old turkey poults were fed a corn and soybean meal-based starter diet supplemented with 0.0 (control), 0.1, 0.2, and 0.3 g/100 g purified putrescine (8 birds/pen, 5 pens/diet). At 14 d of age, half the birds were infected with approximately 43,000 sporulated oocysts. The experiment lasted 24 d. Fecal samples were gathered from d 3 to d 5 postinfection by total collection. Ten control and 10 infected birds fed each diet were sampled on d 6 and d 10 postinfection. The induced infection produced significant depressions in growth and feed intake and detrimental morphological changes in the small intestine of poults in the absence of mortality. Weight gains, protein content of jejunum, and morphometric indices of duodenum, jejunum, and ileum were greater in challenged poults fed 0.3 g/100 g putrescine than in controls. We conclude that dietary putrescine supplementation may be beneficial to poult growth, mucosal development of the small intestine, and to recovery from subclinical coccidiosis.",
"title": "Dietary putrescine (1,4-diaminobutane) influences recovery of Turkey poults challenged with a mixed coccidial infection."
},
{
"docid": "MED-913",
"text": "In recent years, there has been a notable concern on the safety of genetically modified (GM) foods/plants, an important and complex area of research, which demands rigorous standards. Diverse groups including consumers and environmental Non Governmental Organizations (NGO) have suggested that all GM foods/plants should be subjected to long-term animal feeding studies before approval for human consumption. In 2000 and 2006, we reviewed the information published in international scientific journals, noting that the number of references concerning human and animal toxicological/health risks studies on GM foods/plants was very limited. The main goal of the present review was to assess the current state-of-the-art regarding the potential adverse effects/safety assessment of GM plants for human consumption. The number of citations found in databases (PubMed and Scopus) has dramatically increased since 2006. However, new information on products such as potatoes, cucumber, peas or tomatoes, among others was not available. Corn/maize, rice, and soybeans were included in the present review. An equilibrium in the number research groups suggesting, on the basis of their studies, that a number of varieties of GM products (mainly maize and soybeans) are as safe and nutritious as the respective conventional non-GM plant, and those raising still serious concerns, was currently observed. Nevertheless, it should be noted that most of these studies have been conducted by biotechnology companies responsible of commercializing these GM plants. These findings suggest a notable advance in comparison with the lack of studies published in recent years in scientific journals by those companies. All this recent information is herein critically reviewed. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "A literature review on the safety assessment of genetically modified plants."
},
{
"docid": "MED-1674",
"text": "What do the Atkins Diet and the traditional Japanese diet have in common? The Atkins Diet is low in carbohydrate and usually high in fat; the Japanese diet is high in carbohydrate and usually low in fat. Yet both work to promote weight loss. One commonality of both diets is that they both eliminate the monosaccharide fructose. Sucrose (table sugar) and its synthetic sister high fructose corn syrup consist of 2 molecules, glucose and fructose. Glucose is the molecule that when polymerized forms starch, which has a high glycemic index, generates an insulin response, and is not particularly sweet. Fructose is found in fruit, does not generate an insulin response, and is very sweet. Fructose consumption has increased worldwide, paralleling the obesity and chronic metabolic disease pandemic. Sugar (i.e., fructose-containing mixtures) has been vilified by nutritionists for ages as a source of “empty calories,” no different from any other empty calorie. However, fructose is unlike glucose. In the hypercaloric glycogen-replete state, intermediary metabolites from fructose metabolism overwhelm hepatic mitochondrial capacity, which promotes de novo lipogenesis and leads to hepatic insulin resistance, which drives chronic metabolic disease. Fructose also promotes reactive oxygen species formation, which leads to cellular dysfunction and aging, and promotes changes in the brain’s reward system, which drives excessive consumption. Thus, fructose can exert detrimental health effects beyond its calories and in ways that mimic those of ethanol, its metabolic cousin. Indeed, the only distinction is that because fructose is not metabolized in the central nervous system, it does not exert the acute neuronal depression experienced by those imbibing ethanol. These metabolic and hedonic analogies argue that fructose should be thought of as “alcohol without the buzz.”",
"title": "Fructose: It’s “Alcohol Without the Buzz”"
},
{
"docid": "MED-5032",
"text": "The relation between the intake of certain food items thought to be precursors or inhibitors of N-nitroso compounds (NOC) and risk of leukemia was investigated in a case-control study among children from birth to age 10 years in Los Angeles County, California (United States). Cases were ascertained through a population-based tumor registry from 1980 to 1987. Controls were drawn from friends and by random-digit dialing. Interviews were obtained from 232 cases and 232 controls. Food items of principal interest were: breakfast meats (bacon, sausage, ham); luncheon meats (salami, pastrami, lunch meat, corned beef, bologna); hot dogs; oranges and orange juice; and grapefruit and grapefruit juice. We also asked about intake of apples and apple juice, regular and charcoal broiled meats, milk, coffee, and coke or cola drinks. Usual consumption frequencies were determined for both parents and the child. When the risks were adjusted for each other and other risk factors, the only persistent significant associations were for children's intake of hot dogs (odds ratio [OR] = 9.5, 95 percent confidence interval [CI] = 1.6-57.6 for 12 or more hot dogs per month, trend P = 0.01), and fathers' intake of hot dogs (OR = 11.0, CI = 1.2-98.7 for highest intake category, trend P = 0.01). There was no evidence that fruit intake provided protection. While these results are compatible with the experimental animal literature and the hypothesis that human NOC intake is associated with leukemia risk, given potential biases in the data, further study of this hypothesis with more focused and comprehensive epidemiologic studies is warranted.",
"title": "Processed meats and risk of childhood leukemia (California, USA)."
},
{
"docid": "MED-3945",
"text": "The pomegranate fruit ( Punica granatum ) has become an international high-value crop for the production of commercial pomegranate juice (PJ). The perceived consumer value of PJ is due in large part to its potential health benefits based on a significant body of medical research conducted with authentic PJ. To establish criteria for authenticating PJ, a new International Multidimensional Authenticity Specifications (IMAS) algorithm was developed through consideration of existing databases and comprehensive chemical characterization of 45 commercial juice samples from 23 different manufacturers in the United States. In addition to analysis of commercial juice samples obtained in the United States, data from other analyses of pomegranate juice and fruits including samples from Iran, Turkey, Azerbaijan, Syria, India, and China were considered in developing this protocol. There is universal agreement that the presence of a highly constant group of six anthocyanins together with punicalagins characterizes polyphenols in PJ. At a total sugar concentration of 16 degrees Brix, PJ contains characteristic sugars including mannitol at >0.3 g/100 mL. Ratios of glucose to mannitol of 4-15 and of glucose to fructose of 0.8-1.0 are also characteristic of PJ. In addition, no sucrose should be present because of isomerase activity during commercial processing. Stable isotope ratio mass spectrometry as > -25 per thousand assures that there is no added corn or cane sugar added to PJ. Sorbitol was present at <0.025 g/100 mL; maltose and tartaric acid were not detected. The presence of the amino acid proline at >25 mg/L is indicative of added grape products. Malic acid at >0.1 g/100 mL indicates adulteration with apple, pear, grape, cherry, plum, or aronia juice. Other adulteration methods include the addition of highly concentrated aronia, blueberry, or blackberry juices or natural grape pigments to poor-quality juices to imitate the color of pomegranate juice, which results in abnormal anthocyanin profiles. To adjust the astringent taste of poor-quality juice or peel extract, addition of nonpomegranate sugars is a commonly detected adulteration method. The profile generated from these analyses combined with information from existing databases and published literature has been integrated into a validated IMAS for PJ, which can be utilized to detect PJ adulteration. In this survey of commercial pomegranate juices, only 6 of 23 strictly met all of the IMAS criteria.",
"title": "International multidimensional authenticity specification (IMAS) algorithm for detection of commercial pomegranate juice adulteration."
},
{
"docid": "MED-4188",
"text": "Depressive disorders are very common in clinical practice, with approximately 11.3 of all adults afflicted during any a year. Saffron is the world's most expensive spice and apart from its traditional value as a food additive, recent studies indicate several therapeutic effects for saffron. It is used for depression in Persian traditional medicine. Our objective was to compare the efficacy of hydro-alcoholic extract of Crocus sativus (stigma) with fluoxetine in the treatment of mild to moderate depression in a 6-week double-blind, randomized trial. Forty adult outpatients who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition for major depression based on the structured clinical interview for DSM-IV and with mild to moderate depression participated in the trial. In this double-blind, single-center trial and randomized trial, patients were randomly assigned to receive capsules of saffron 30 mg/day (BD) (Group 1) and capsule of fluoxetine 20 mg/day (BD) (Group 2) for a 6-week study. Saffron at this dose was found to be effective similar to fluoxetine in the treatment of mild to moderate depression (F = 0.13, d.f. = 1, P = 0.71). There were no significant differences in the two groups in terms of observed side effects. The results of this study indicate the efficacy of Crocus sativus in the treatment of mild to moderate depression. A large-scale trial is justified.",
"title": "Hydro-alcoholic extract of Crocus sativus L. versus fluoxetine in the treatment of mild to moderate depression: a double-blind, randomized pilot tr..."
},
{
"docid": "MED-5284",
"text": "Objective Habitual chocolate intake was recently found to be associated with lower body weight in three cross-sectional epidemiological studies. Our objective was to assess whether these cross-sectional results hold up in a more rigorous prospective analysis. Methods We used data from the Atherosclerosis Risk in Communities cohort. Usual dietary intake was assessed by questionnaire at baseline (1987–98), and after six years. Participants reported usual chocolate intake as the frequency of eating a 1-oz (∼28 g) serving. Body weight and height were measured at the two visits. Missing data were replaced by multiple imputation. Linear mixed-effects models were used to evaluate cross-sectional and prospective associations between chocolate intake and adiposity. Results Data were from 15,732 and 12,830 participants at the first and second visit, respectively. More frequent chocolate consumption was associated with a significantly greater prospective weight gain over time, in a dose-response manner. For instance, compared to participants who ate a chocolate serving less often than monthly, those who ate it 1–4 times a month and at least weekly experienced an increase in Body Mass Index (kg/m2) of 0.26 (95% CI 0.08, 0.44) and 0.39 (0.23, 0.55), respectively, during the six-year study period. In cross-sectional analyses the frequency of chocolate consumption was inversely associated with body weight. This inverse association was attenuated after excluding participants with preexisting obesity-related illness. Compared to participants without such illness, those with it had higher BMI and reported less frequent chocolate intake, lower caloric intake, and diets richer in fruits and vegetables. They tended to make these dietary changes after becoming ill. Conclusions Our prospective analysis found that a chocolate habit was associated with long-term weight gain, in a dose-response manner. Our cross-sectional finding that chocolate intake was associated with lower body weight did not apply to participants without preexisting serious illness.",
"title": "Habitual Chocolate Consumption May Increase Body Weight in a Dose-Response Manner"
},
{
"docid": "MED-3308",
"text": "An occupational health survey conducted in a workshop in which asbestos cement was used showed initial atmospheric asbestos levels ranging from 1.9 to 27.5 fibres per millilitre of air. Radiological changes suggestive of asbestos-related pleural disease were found in 2 workers (2.5%), while 3 (3.8%) had borderline features of asbestosis. The survey confirmed that uncontrolled and hazardous use of asbestos continues in industry despite public awareness of its dangers and the Asbestos Regulations of 1987.",
"title": "Third wave of asbestos-related disease from secondary use of asbestos. A case report from industry."
},
{
"docid": "MED-4825",
"text": "Pancreatic cancer kills more than 250,000 people each year worldwide and has a poor prognosis. The aim of this article is to critically review the epidemiologic evidence for exposures that may either increase or decrease the risk. A Medline search was performed for epidemiologic studies and reviews published up to April 2007. Consistent evidence of a positive association was found for family history and cigarette smoking. Many studies documented a positive association with diabetes mellitus and chronic pancreatitis, although the etiologic mechanisms are unclear. Other associations were detected, but the results were either inconsistent or from few studies. These included positive associations with red meat, sugar, fat, body mass index, gallstones, and Helicobacter pylori, and protective effects of increasing parity, dietary folate, aspirin, and statins. There was no evidence linking alcohol or coffee consumption with an increased risk of pancreatic cancer. The associations with many exposures need to be clarified from further epidemiologic work in which there is both precise measurement of risk factors, adjustment for potential confounders, and, for dietary studies, information recorded on the method of food preparation and pattern of consumption. Such work is important to reduce the incidence of this fatal disease.",
"title": "Pancreatic cancer: a review of the evidence on causation."
},
{
"docid": "MED-4178",
"text": "A method has been developed to identify pesticide residues and foodstuffs for inclusion in national monitoring programs with different priority levels. It combines two chronic dietary intake indicators: ATMDI based on maximum residue levels and agricultural uses, and EDI on food contamination data. The mean and 95th percentile of exposure were calculated for 490 substances using individual and national consumption data. The results show that mean ATMDI exceeds the acceptable daily intake (ADI) for 10% of the pesticides, and the mean upper-bound EDI is above the ADI for 1.8% of substances. A seven-level risk scale is presented for substances already analyzed in food in France and substances not currently sought. Of 336 substances analyzed, 70 pesticides of concern (levels 2-5) should be particularly monitored, 22 of which are priority pesticides (levels 4 and 5). Of 154 substances not sought, 36 pesticides of concern (levels 2-4) should be included in monitoring programs, including 8 priority pesticides (level 4). In order to refine exposure assessment, analytical improvements and developments are needed to lower the analytical limits for priority pesticide/commodity combinations. Developed nationally, this method could be applied at different geographic scales. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Chronic dietary risk characterization for pesticide residues: a ranking and scoring method integrating agricultural uses and food contamination data."
}
] |
4482
|
How is not paying off mortgage better in normal circumstances?
|
[
{
"docid": "375438",
"text": "One way of looking at it is that your equity in your house is an investment in a particular class of asset, and investing further in that asset class may drive you away from, rather than towards, your preferred asset mix. It's pretty common here in New Zealand for people's only investments to be their homes and rental properties. I wish those people luck when our current property boom ends.",
"title": ""
},
{
"docid": "537721",
"text": "Lets do the math, using your numbers. We start off with $100K, a desire to buy a house and invest, and 30 years to do it. Scenario #1 We buy a house for $100K mortgage at 5% interest over 30 years. Monthly payment ends up being $536.82/month. We then take the $100K we still have and invest it in stocks, earning an average of 9% annually and paying 15% taxes. Scenario #2 We buy a house for our $100K cash, and then, every month, we invest the $536.82 we would have paid for the mortgage. Again, investments make 9% annually long term, and we pay 15% taxes. How would it look in 30 years? Scenario #1 Results: 30 years later we would have a paid off house and $912,895 in investments Scenario #2 Results: 30 years later we would have a paid off house and $712,745 in investments Conclusion: NOT paying off your mortgage early results in an additional $200,120 in networth after 30 years. That's 28% more. Therefore, not paying off your mortgage is the superior scenario. Caveats/Notes/Things to consider Play with the numbers yourself:",
"title": ""
},
{
"docid": "287656",
"text": "\"In some respects the analysis for this question is similar to comparing a \"\"safe\"\" return on a government bond vs. holding the stock market. Typically, the stock market's expected return will be higher -- i.e., there's a positive equity risk premium -- vs. a government bond (assuming it's held to maturity). There's no guarantee that the stock market will outperform, although the probability of outperformance rises (some analysts argue) the longer the holding period for equities beyond, say, 10 years. That's why there's generally a positive equity risk premium, otherwise no one (or relatively few investors) would hold equities.\"",
"title": ""
},
{
"docid": "169171",
"text": "There are several reasons:",
"title": ""
},
{
"docid": "542463",
"text": "Certainly there are people who do pay off their homes. Others do not. It's a question of risk tolerance and preference. Some considerations relevant to this question: Taxes - Interest on a mortgage is tax deductible. Particularly for high earners, this is a significant incentive to maintain a mortgage balance and place extra money in the market instead. Liquidity - If you lose your job, you can sell stocks to pay the mortgage. But if you have made principle payments on your mortgage but still owe some outstanding balance, you are still required to make monthly payments without any source of income. Rates - In recent years it is been common to get a mortgage for 3.2% to 3.5%. The difference between those rates and 9% rate of return for the market is substantial. There are other considerations but the answer in the end is that for many people the risk / reward calculus says the ~5% difference in rate of return is worth the potential risks.",
"title": ""
},
{
"docid": "356100",
"text": "\"The reason is that although the American economy is functioning normally, mortgage rates are stupid-low, and are below a prudent expectation of long-term (30 year) rates of return in the market. I manage endowments, so I say \"\"prudent\"\" in the context of endowment investment, which is the picture of caution and subject to UPMIFA law (the P being prudent). What's more, there are tax benefits. Yes, you pay 15% long-term capital gains tax on investment income. But your mortgage interest is tax deductible at your \"\"tax bracket\"\" rate of 25, 28 or 33% - this being the tax you would pay on your next dollar of earned income. And in the early years of a mortgage, mortgage payments are nearly 100% interest. So even if it's a wash: you gain $10k in the market but pay $10k in mortgage interest -- you pay $1500 tax on the gains, but the interest deduction redudes tax by $2800. So you are still $1300 ahead. TLDR: the government pays us to do this.\"",
"title": ""
}
] |
[
{
"docid": "454287",
"text": "\"None of what I say is advice directed to you. It is how I would continue to analyse the situation you have, were it mine. First off, I prefer to work in certainties more than possibilities. Saying that, paying down the mortgage makes sense as I can calculate the amount I will save. I also believe that rate rises are coming in the future, based on the talk from the BofE, so any money I pay off now means guaranteed less interest to pay in the future. Also, the lower my loan-to-value ratio, the better/lower interest rates I can receive in the mortgage market. If I do not want to work until retirement age, it'd be nice to have as few bills as possible in the decade or so prior to retirement age. I could then do early-retirement or part-time work in the run-up to retirement. I could use my savings to fund life until retirement pays out. I'd be aiming to put 15% of my gross income into \"\"future investing\"\" - using ISAs to build up a savings pot, taking advantage of retirement products. That way all the money is not tied to a normal retirement age before it can accessed. And it's not touchable by future greedy Government taxation... Any income leftover above the 15%, I'd be throwing at the mortgage - taking advantage of the 10% overpay window, remortgaging as LTV comes down. In theory, overpaid mortgage equity is money that could still be accessed (provided house prices don't decline and remortgaging is a possibility). So, in short, I'd follow a plan along these lines of logic. 1) Make sure I have 4-6 months of living expenses as a Rainy Day Fund. Insulate myself from fluctuations in my financial situation. 2) Put away 15% of annual gross income towards \"\"future saving\"\". ISAs first, pension second. 3) Overpay the mortgage and look to remortgage as LTV drops. When LTV nears 60%, look to lock in to a longer-term fix. eg. 2 year fixes at 90% LTV, 5 year fixes at 60%. 4) Reassess steps 2 & 3 as life happens, circumstances change, work fluctuates, etc. 5) Once the mortgage is paid off, build as much wealth as possible - ISAs first, then non-tax efficient savings products. Aim for keeping expenses down and raising my savings % rate as much as possible. [Your analysis was thorough and shows you are thinking through consequences. Never forget to factor in the risk of carrying debt. Having no/low debt as you get older means there's more income left to build wealth. Ignore the American view of carrying debt for life and trusting investments to outperform the debt. You have to pay monthly to keep that debt around - and it ain't a pet!]\"",
"title": ""
},
{
"docid": "556072",
"text": "It depends what rate mortgage you can get for any extra loans... If you remortgage you are likely to get a rate of 3.5-4%... depending who you go with. With deposit accounts in the UK maying around 1% (yes, you can get more by tying it up for longer but not a huge amount more) clearly you're better off not having a mortgage rather than money in the bank. Does your 8k income allow for tax? If it does, you are getting 6% return on the money tied up in the flat. If you are getting 6% after tax on the invested money, that's way better than you would get on any left over cash paid into an investment. Borrowing money on a mortgage would cost you less than 6%... so you are better off borrowing rather than selling the flat. If you are getting 6% before tax... depending on your tax rate... it probably makes very little difference. You'd need to work out how much an extra 80k mortgage would cost you, how much the 50k on deposit would earn you and how much you make after tax. There is a different route. Set up a mortgage on the rental flat. You can claim the interest payment off the flat's income... reduce your tax bill so the effective mortgage rate on the flat would be less than what you could get with a mortgage on the new house. Use the money from the flat's mortgage to finance the difference in house price. In fact from a tax view, you may be better off having a mortgage free house and maxing out the mortgage on the flat so you can write off as much as possible against your tax bill. All of the above assume ... that the flat is rented all the time. The odd dry spell on the flat could influence the sums a lot. All of the above assume that your cash flow works whichever route you choose. As no-one on stack exchange has all of the numbers for your specific circumstances it may be worth talking to a tax accountant. They could advise you properly, knowing the numbers, which makes the best sense for you in terms of overall cost, cash flow, risk and so on.",
"title": ""
},
{
"docid": "150607",
"text": "\"In England, currently and for most of the last fifty years, the standard length of the mortgage term is 25 years. A mortgage can be either a capital-and-interest mortgage, or interest-only. In the former, you pay off part of the original loan each month, plus the interest on the amount borrowed. In the latter, you only pay interest each month, and the original amount borrowed never reduces: you pay premiums on a life insurance policy, additionally, which is designed to pay off the original sum borrowed at the end of the 25 years. No one in England thinks that a 25 year loan has any drawbacks. The main point to appreciate is that the longer the period of the loan, the less you need to pay each month, because you are repaying the original loan - the capital - over a longer period of time. Thus, in principle, a mortgage is easier to repay the longer the term is, because the monthly payment is less. If you have a 12 year mortgage, you must pay back the original amount borrowed in half the time: the capital element in your payment each month is double what it would be if repaid over 25 years - i.e. if repaid over a period twice as long. Only if the borrower is less than 25 years away from retirement is a 25 years mortgage seen as a bad idea, by the lender - because, obviously, the lender relies on the borrower having an income sufficient to keep up the repayments. There are many complicating factors: an interest-only mortgage, where you pay back the original amount borrowed from the maturity proceeds from a life policy, puts you in a situation where the original capital sum never reduces, so you always pay the same each month. But on a straight repayment mortgage, the traditional type, you pay less and less each month as time goes by, for you are reducing the capital outstanding each month, and because that is reducing so is the amount of interest you pay each month (as this is calculated on the outstanding capital amount). There are snags to avoid, if you can. For example, some mortgage contracts impose penalties if the borrower repays more than the due monthly amount, hence in effect the borrower faces a - possibly heavy - financial penalty for early repayment of the loan. But not all mortgages include such a condition. If house prices are on a rising trend, the market value of the property will soon be worth considerably more than the amount owed on the mortgage, especially where the mortgage debt is reducing every month, as each repayment is made; so the bank or other lender will not be worried about lending over a 25 year term, because if it forecloses there should normally be no difficulty in recovering the outstanding amount from the sale proceeds. If the borrower falls behind on the repayments, or house prices fall, he may soon get into difficulties; but this could happen to anyone - it is not a particular problem of a 25 year term. Where a default in repayment occurs, the bank will often suggest lengthening the mortgage term, from 25 years to 30 years, in order to reduce the amount of the monthly repayment, as a means of helping the borrower. So longer terms than 25 years are in fact a positive solution in a case of financial difficulty. Of course, the longer the term the greater the amount that the borrower will pay in total. But the longer the term, the less he will pay each month - at least on a traditional capital-and-interest mortgage. So it is a question of balancing those two competing factors. As long as you do not have a mortgage condition that penalises the borrower for paying off the loan more quickly, it can make sense to have as long a term as possible, to begin with, which can be shortened by increasing the monthly repayment as fast as circumstances allow. In England, we used to have tax relief on mortgage payments, and so in times gone by it did make sense to let the mortgage run the full 25 years, in order to get maximum tax relief - the rules were very complex, but it tended to maximise your tax relief by paying over the longest possible period. But today, with no income tax relief given on mortgage payments, that is no longer a consideration in this country. The practical position is, of course, that you can never tell how long it might take you to pay off a mortgage. It is a gamble as to whether your income will rise in future years, and whether your job will last until your mortgage is paid off. You might fall ill, you might be made redundant, you might be demoted. Mortgage interest rates might rise. It is never possible to say that you \"\"can\"\" pay off the loan in a short time. If you hope to do so, the only matters that actually fall within your control are the conditions of the mortgage contract itself. Get a good lawyer. Tell him to watch out for early-redemption penalties. Get a good financial adviser. Tell him to work out what you will need to pay in additional premiums on your life policy if you are considering taking an interest-only mortgage. Try to fix your mortgage rate in the first few years, for as long as possible, so that in your most vulnerable period, with the greatest amount owing, you are insulated against unexpected interest rate fluctuations. Only the initial conditions can be controlled, so it might be prudent to take as long a term as possible, even though a prudent borrower will leave himself room to reduce that term, and a prudent lender will leave room to extend it, in case of unpredictable changes in the financial circumstances. In England, most lenders are, in my experience, reluctant to grant mortgages for less than 25 years. That is simply a policy. Rightly or wrongly, the borrower usually has no choice about the length of the mortgbage term. Hence, in the UK it can be difficult to find a choice of interest rates based on differing mortgage terms. I am aware that the situation in the USA is rather different, but if I personally were faced with the choice I would be uncomfortable about taking on a short term mortgage, because of the factors I have outlined above.\"",
"title": ""
},
{
"docid": "599499",
"text": "This is more of an interesting question then it looks on first sight. In the USA there are some tax reliefs for mortgage payments, which we don’t have in the UK unless you are renting out the property with the mortgage. So firstly work out the interest rate on each loan taking into account any tax reliefs, etc. Then you need to consider the charges for paying off a loan, for example often there is a charge if you pay off a mortgage. These days in the UK, most mortgagees allow you to pay off at least 10% a year without hitting such a charge – but check your mortgage offer document. How interest is calculated when you make an early payment may be different between your loans – so check. Then you need to consider what will happen if you need another loan. Some mortgages allow you to take back any overpayments, most don’t. Re-mortgaging to increase the size of your mortgage often has high charges. Then there is the effect on your credit rating: paying more of a loan each month then you need to, often improves your credit rating. You also need to consider how interest rates may change, for example if you mortgage is a fixed rate but your car loan is not and you expect interest rates to rise, do the calculations based on what you expect interest rates to be over the length of the loans. However, normally it is best to pay off the loan with the highest interest rate first. Reasons for penalties for paying of some loans in the UK. In the UK some short term loans (normally under 3 years) add on all the interest at the start of the loan, so you don’t save any interest if you pay of the loan quicker. This is due to the banks having to cover their admin costs, and there being no admin charge to take out the loan. Fixed rate loans/mortgagees have penalties for overpayment, as otherwise when interest rates go down, people will change to other lenders, so making it a “one way bet” that the banks will always loose. (I believe in the USA, the central bank will under right such loans, so the banks don’t take the risk.)",
"title": ""
},
{
"docid": "243065",
"text": "\"This is a very complicated thing to try to do. There are many variables, and some will come down to personal taste and buying habits. First you need to look at each of the loans and find out two very important things. Some times you pay a huge penalty for paying off a loan early. Usually this is on larger loans (like your mortgage) but it's not on heard of in car loans. If there is a penalty for early re-payment, then just pay off on the schedule, or at least take that penalty into consideration. Another dirty trick that some banks do is force you to pay \"\"the interest first\"\" when making a early payment. Essentially this is a penalty that ensures you pay the \"\"full price\"\" of the loan and not a lessor amount because you borrowed for less time. The way it really works is complicated, but it's not usually to your benefit to pay these off early either. These usually show up on smaller loans, but better look for it anyway. Next up on the list you need to look at your long term goals and buying habits. When are you going to re-model your kitchen. You can get another loan on the equity of the house, it's much harder to get a loan on the equity of a car (even once the car is paid off). So, depending on your goals you may do better to pay extra into your mortgage, then paying off your other loans early. Also consider your credit score. A big part of it is amount of money remaining on credit lines/total credit lines. Paying of a loan will reduce your credit score (short term). It will also give you the ability to take out another loan (long term). Finally, consider simplification of debtors. If something goes wrong it's much easier to work with a single debtor, then three separate debtors. This could mean moving your car loans into your mortgage, even if it's at a higher interest rate, should the need arise. Should you need to do that you will need the equity in your home. Bonus Points: As others have stated, there are tax breaks for people with mortgages in some circumstances. You should consider those as well. Car loans usually require a different level of insurance. Make sure to count that as well. Taking these points into consideration, I would suggest, paying off the 2.54% car loan first, then putting the extra $419.61 into your mortgage to build up more equity, and leaving the 0% loan to run it's full course. You all ready \"\"paid for\"\" that loan, so might as well use it. Side note: If you can find a savings account or other investment platform with a decent enough interest rate, you would be better served putting the $419.61 there. A decent rate ROTH-IRA would work very nicely for this, as you would get tax deferment on that as well. Sadly it may be hard to find an account with a high enough interest rate to make it a more attractive option the paying off the mortgage early.\"",
"title": ""
},
{
"docid": "119351",
"text": "\"I've heard that the bank may agree to a \"\"one time adjustment\"\" to lower the payments on Mortgage #2 because of paying a very large payment. Is this something that really happens? It's to the banks advantage to reduce the payments in that situation. If they were willing to loan you money previously, they should still be willing. If they keep the payments the same, then you'll pay off the loan faster. Just playing with a spreadsheet, paying off a third of the mortgage amount would eliminate the back half of the payments or reduces payments by around two fifths (leaving off any escrow or insurance). If you can afford the payments, I'd lean towards leaving them at the current level and paying off the loan early. But you know your circumstances better than we do. If you are underfunded elsewhere, shore things up. Fully fund your 401k and IRA. Fill out your emergency fund. Buy that new appliance that you don't quite need yet but will soon. If you are paying PMI, you should reduce the principal down to the point where you no longer have to do so. That's usually more than 20% equity (or less than an 80% loan). There is an argument for investing the remainder in securities (stocks and bonds). If you itemize, you can deduct the interest on your mortgage. And then you can deduct other things, like local and state taxes. If you're getting a higher return from securities than you'd pay on the mortgage, it can be a good investment. Five or ten years from now, when your interest drops closer to the itemization threshold, you can cash out and pay off more of the mortgage than you could now. The problem is that this might not be the best time for that. The Buffett Indicator is currently higher than it was before the 2007-9 market crash. That suggests that stocks aren't the best place for a medium term investment right now. I'd pay down the mortgage. You know the return on that. No matter what happens with the market, it will save you on interest. I'd keep the payments where they are now unless they are straining your budget unduly. Pay off your thirty year mortgage in fifteen years.\"",
"title": ""
},
{
"docid": "233472",
"text": "Other people have belabored the point that you will get a better rate on a 15 year mortgage, typically around 1.25 % lower. The lower rate makes the 15 year mortgage financially wiser than paying a 30 year mortgage off in 15 years. So go with the 15 year if your income is stable, you will never lose your job, your appliances never break, your vehicles never need major repairs, the pipes in your house never burst, you and your spouse never get sick, and you have no kids. Or if you do have kids, they happen to have good eyesight, straight teeth, they have no aspirations for college, don't play any expensive sports, and they will never ask for help paying the rent when they get older and move out. But if any of those things are likely possibilities, the 30 year mortgage would give you some flexibility to cover short term cash shortages by reverting to your normal 30 year payment for a month or two. Now, the financially wise may balk at this because you are supposed to have enough cash in reserves to cover stuff like this, and that is good advice. But how many people struggle to maintain those reserves when they buy a new house? Consider putting together spreadsheet and calculating the interest cost difference between the two strategies. How much more will the 30 year mortgage cost you in interest if you pay it off in 15 years? That amount equates to the cost of an insurance policy for dealing with an occasional cash shortage. Do you want to pay thousands in extra interest for that insurance? (it is pretty pricey insurance) One strategy would be to go with the 30 year now, make the extra principal payments to keep you on a 15 year schedule, see how life goes, and refinance to a 15 year mortgage after a couple years if everything goes well and your cash reserves are strong. Unfortunately, rates are likely to rise over the next couple years, which makes this strategy less attractive. If at all possible, go with the 15 year so you lock in these near historic low rates. Consider buying less house or dropping back to the 30 year if you are worried that your cash reserves won't be able to handle life's little surprises.",
"title": ""
},
{
"docid": "333219",
"text": "\"All of the provided advice is great, but a slightly different viewpoint on debt is worth mentioning. Here are the areas that you should concentrate your efforts and the (rough) order you should proceed. Much of the following is predicated upon your having a situation where you need to get out of debt, and learn to better budget and control your spending. You may already have accomplished some of these steps, or you may prioritize differently. Many people advise prioritizing contributing to a 401(k) savings plan. But with the assumption that you need advise because you have debt trouble, you are probably paying absurd interest rates, and any savings you might have will be earning much lower rates than you are paying on consumer debt. If you are already contributing, continue the plan. But remember, you are looking for advice because your financial situation is in trouble, so you need to put out the fire (your present problem), and learn how to manage your money and plan for the future. Compose a budget, comprised of the following three areas (the exact percentages are fungible, fit them to your circumstances). Here is where planning can get fun, when you have freed yourself from debt, and you can make choices that resonate with your individual goals. Once you have \"\"put out the fire\"\" of debt, then you should do two things at the same time. As you pay off debt (and avoid further debt), you will find that saving for both independence and retirement become easier. The average American household may have $8000+ credit card debt, and at 20-30%, the interest payments are $150-200/month, and the average car payment is nearly $500/month. Eliminate debt and you will have $500-800/month that you can comfortably allocate towards retirement. But you also need to learn (educate yourself) how to invest your money to grow your money, and earn income from your savings. This is an area where many struggle, because we are taught to save, but we are not taught how to invest, choose investments wisely and carefully, and how to decide our goals. Investing needs to be addressed separately, but you need to learn how. Live in an affordable house, and pay off your mortgage. Consider that the payment on a mortgage on even a modest $200K house is over $1000/month. Combine saving the money you would have paid towards a mortgage payment with the money you would have paid towards credit card debt or a car loan. Saving becomes easy when you are freed from these large debts.\"",
"title": ""
},
{
"docid": "282816",
"text": "You almost never want to repay a pre-2012 student loan early. As you've realised, you can put the money in an ISA instead and earn more interest than you're paying on the loan. If you withdrew money from the ISA each month to replace the repayments being taken from your salary, there'd be money left in the ISA when you finished repaying the loan. This is also the cheapest debt you'll ever have, so if you repay it now and then end up borrowing money elsewhere in the future, you'll probably be worse off. In particular, if you expect to have a mortgage at some point, you'll probably be better off keeping the money to add to a deposit rather than repaying it now and then borrowing more on the mortgage. You should also consider how long it'll take you to repay the loan normally. If you don't expect to finish repaying within 25 years, you'd be throwing money away by repaying early. This is more of an issue for the larger post-2012 loans.",
"title": ""
},
{
"docid": "154181",
"text": "Why won't anyone just answer the original question? The question was not about opportunity cost or flexibility or family expenses. There are no right answers to any of those things and they all depend on individual circumstances. I believe the answer to the question of whether paying off a 30-year mortgage in 15 years would cost the same amount as a 15-year mortgage of the same interest rate is yes but ONLY if you pay it off on the exact same schedule as your supposed 15-year. In reality, the answer is NO for two reasons: the amortization schedule; and the fact that the 30-year will always have a higher interest rate than the 15-year. The way mortgages are amortized, the interest is paid first, essentially. For most people the majority of the monthly payment is interest for the first half of the loan's life. This is good for most people because, in reality, most mortgages only last a couple years after which people refinance or move and for those first couple years the majority of one's housing costs (interest) are tax deductible. It is arguable whether perpetuating this for one's entire life is wise... but that's the reality of most mortgages. So, unless you pay off your 30-year on the exact same amortization schedule of your theoretical 15-year, you will pay more in interest. A common strategy people pursue is paying an extra monthly payment (or more) each year. By the time you get around to chipping away at your principal in that way, you will already have paid a lot more interest than you would have on a 15-year. And, really, if you can afford to substantially pay down principal in the first year or two of your mortgage, you probably should've borrowed less money to begin with. In theory, IF the rates were the same (they're not) and IF you paid the 30 off every month in the EXACT same way as you would've paid a 15 (you won't) you will pay the same amount in the end. You have to decide if the flexibility is worth more to you than the cost savings. For example: a 300k mortgage at 3.5% will have a monthly payment of ~$2150 for a 15-year and ~$1350 for a 30-year, both will start with ~$875/month of that being in interest (gradually declining with time). What I think most people undervalue is the freedom and peace of mind that comes with a paid off or nearly paid off home... and 15 years is a lot more tangible than 30, plus a lot cheaper over all. If you can afford a 15-year mortgage without putting too much stress on your budget, it is definitely the better option for financial security. And be careful of the index fund opportunity cost advice. On average it may be a good idea when you look at the very long run, historically, but a lot of people get less than average returns depending on when they buy and what the market does in the short run. There is no certainty around what returns you will get from the stock market, but if you have a 30-year mortgage there is a lot of certainty around what you will owe every month for the next 30-years. Different mixes of investments make sense for different people, and most people would be wise to get some exposure to the stock market for its returns and liquidity. However, if someone's goal is borrowing more money for their house in order to invest more money in the stock market for their retirement, they would actually be better served in achieving security and independence 15 years sooner.",
"title": ""
},
{
"docid": "323475",
"text": "First off, putting extra cash toward a mortgage early on, when most of the payments are going to interest, is the BEST time. If you pay an extra $1 on your mortgage today, you will save 30 years worth of interest (assuming a 30 year mortgage). If in 29 years you pay an extra dollar, you will only save 1 year worth of interest. That said, there are lots of things that go into a decision like this. Do you have other debts? How stable is your income? What is the interest rate on your mortgage compared to any other debts you may have or potential investments you might make? How much risk are you willing to take? Etc. Mortgages tend to be very low interest, and, at least in the U.S., the interest on them is tax-deductible, making the effective interest rate even lower. If you have some other loan, you are almost always better to pay the other loan off first. If you don't mind a little risk, you are usually better off to invest your money rather than pay off the mortgage. Suppose your mortgage is 5%. The average return on the stock market is something like 7% (according to my buddy who works for Wells Fargo). So if you put $1000 toward your mortgage, you'd save $50 the first year. (Ignoring compounding for simplicity, changes the exact numbers but not the basic idea.) If you put that same $1000 in the stock market, than if it's a typical year you'd make $70. You could put $50 of that toward paying the interest on your mortgage and you'd have $20 left to go on a wild spending spree. The catch is that the interest on a mortgage is fixed, while the return on an investment is highly variable. In an AVERAGE year the stock market might return 7%, but this year it might return 20% or it might lose 10% or a wide range of other possible numbers. (Well, you might have a variable rate mortgage, but there are still usually some defined limits on how much it can vary.)",
"title": ""
},
{
"docid": "65532",
"text": "The first thing you need to do is look at your terms and conditions of your credit card, or ask your bank, how they will apply the payments. As Dilip notes in his answer, in the US, they will likely apply the minimum payment to the lower rate balance, and then must apply the rest above the minimum to the higher rate balance. In other countries, this will vary by law and custom. Do not assume it will pay off the higher balance, or proportionally, without asking. Let's take the following example. You owe $6000. $5000 is at 13.5% (normal purchase rate) and $1000 is at 22% (cash advance rate). If your bank applies payments to both balances proportionally, then a payment of $600 will reduce your purchase balance by $500 and your cash advance balance by $100. The average APR, then, is simply sum of the product of the APR times balance. So here, (.135*5000 + .225*1000)/6000 = 15%. This is called a weighted average. If the bank applies the payment differently - such as to the lower rate first, or some specified part to the lower rate and the rest to the higher rate - then this will be misleading if you enter it into a calculator, because your average APR will rise over time as you pay off the purchase balance but don't pay off the cash advance balance, or may decrease if the opposite happens. The weighted average is probably reasonably close in the circumstance that you describe, even if you have rules applying the balance differently, so long as they don't 100% pay down the lower rate - so it may be the simplest option for you in terms of rough calculations (where it's not critical to be correct, just close). One approach using the online calculators that might be better, is to treat these like two separate loans/cards. Many calculators exist for multiple balances. Then you can allocate funds differently to the two 'cards'. This would allow you to see how long you will need until you've paid off the higher balance, for example, although it probably won't perfectly match things - unless you find a site that has this specific option available you probably will have to either live with a small error in your calculations or do the math by hand.",
"title": ""
},
{
"docid": "135005",
"text": "The set of circumstances that 401k loans make sense, are very small. As you would expect yours is not one of them. You make 70K per year and need 6500. Interest rate is not your problem, budgeting is the problem. Pay this off in three months not the 48 you are proposing. Why is borrowing from your 401K a bad idea, especially in this case? Look, been there done that, been the over spender. The sooner that you learn how to handle your money the better. I was in my 40s when I learned, if you can do this now you can be really wealthy by the time you get to be my age. Dream a bit. How much margin would you have in your life if you were able to pay this off in 3 months? How much better would your life be? Go forth and do great things. I believe in you.",
"title": ""
},
{
"docid": "104857",
"text": "\"A re-financing, or re-fi, is when a debtor takes out a new loan for the express purpose of paying off an old one. This can be done for several reasons; usually the primary reason is that the terms of the new loan will result in a lower monthly payment. Debt consolidation (taking out one big loan at a relatively low interest rate to pay off the smaller, higher-interest loans that rack up, like credit card debt, medical bills, etc) is a form of refinancing, but you most commonly hear the term when referring to refinancing a home mortgage, as in your example. To answer your questions, most of the money comes from a new bank. That bank understands up front that this is a re-fi and not \"\"new debt\"\"; the homeowner isn't asking for any additional money, but instead the money they get will pay off outstanding debt. Therefore, the net amount of outstanding debt remains roughly equal. Even then, a re-fi can be difficult for a homeowner to get (at least on terms he'd be willing to take). First off, if the homeowner owes more than the home's worth, a re-fi may not cover the full principal of the existing loan. The bank may reject the homeowner outright as not creditworthy (a new house is a HUGE ding on your credit score, trust me), or the market and the homeowner's credit may prevent the bank offering loan terms that are worth it to the homeowner. The homeowner must often pony up cash up front for the closing costs of this new mortgage, which is money the homeowner hopes to recoup in reduced interest; however, the homeowner may not recover all the closing costs for many years, or ever. To answer the question of why a bank would do this, there are several reasons: The bank offering the re-fi is usually not the bank getting payments for the current mortgage. This new bank wants to take your business away from your current bank, and receive the substantial amount of interest involved over the remaining life of the loan. If you've ever seen a mortgage summary statement, the interest paid over the life of a 30-year loan can easily equal the principal, and often it's more like twice or three times the original amount borrowed. That's attractive to rival banks. It's in your current bank's best interest to try to keep your business if they know you are shopping for a re-fi, even if that means offering you better terms on your existing loan. Often, the bank is itself \"\"on the hook\"\" to its own investors for the money they lent you, and if you pay off early without any penalty, they no longer have your interest payments to cover their own, and they usually can't pay off early (bonds, which are shares of corporate debt, don't really work that way). The better option is to keep those scheduled payments coming to them, even if they lose a little off the top. Often if a homeowner is working with their current bank for a lower payment, no new loan is created, but the terms of the current loan are renegotiated; this is called a \"\"loan modification\"\" (especially when the Government is requiring the bank to sit down at the bargaining table), or in some cases a \"\"streamlining\"\" (if the bank and borrower are meeting in more amicable circumstances without the Government forcing either one to be there). Historically, the idea of giving a homeowner a break on their contractual obligations would be comical to the bank. In recent times, though, the threat of foreclosure (the bank's primary weapon) doesn't have the same teeth it used to; someone facing 30 years of budget-busting payments, on a house that will never again be worth what he paid for it, would look at foreclosure and even bankruptcy as the better option, as it's theoretically all over and done with in only 7-10 years. With the Government having a vested interest in keeping people in their homes, making whatever payments they can, to keep some measure of confidence in the entire financial system, loan modifications have become much more common, and the banks are usually amicable as they've found very quickly that they're not getting anywhere near the purchase price for these \"\"toxic assets\"\". Sometimes, a re-fi actually results in a higher APR, but it's still a better deal for the homeowner because the loan doesn't have other associated costs lumped in, such as mortgage insurance (money the guarantor wants in return for underwriting the loan, which is in turn required by the FDIC to protect the bank in case you default). The homeowner pays less, the bank gets more, everyone's happy (including the guarantor; they don't really want to be underwriting a loan that requires PMI in the first place as it's a significant risk). The U.S. Government is spending a lot of money and putting a lot of pressure on FDIC-insured institutions (including virtually all mortgage lenders) to cut the average Joe a break. Banks get tax breaks when they do loan modifications. The Fed's buying at-risk bond packages backed by distressed mortgages, and where the homeowner hasn't walked away completely they're negotiating mortgage mods directly. All of this can result in the homeowner facing a lienholder that is willing to work with them, if they've held up their end of the contract to date.\"",
"title": ""
},
{
"docid": "243520",
"text": "\"Check the terms of your mortgage. If you are in a fixed-term mortgage, you can likely \"\"over-pay\"\" a fixed amount of the capital each year: typically 10%. Eg if you owe £300,000 on the mortgage, you can pay off an additional £30,000 this year. Next year you'd owe something like £260,000 so could pay off £26,000. You'd need to check the terms of your mortgage to see what this limit is. You can actually pay off more than this, but would become liable to pay an \"\"early repayment fee\"\" or similar, which is usually something like 3-5% of the mortgage amount. Note that this usually means you would need to re-finance the mortgage anyway If you are not on a fixed-term mortgage than, in the UK at least, you are pretty much free to over-pay as much as you would like or refinance the mortgage. If you are in a fixed-term mortgage, it is usually better to simply over-pay by that maximum allowed amount until the fixed period ends, at which point you can re-finance onto a mortgage that allows higher overpayments. This isn't always the case, though, depending on your interest rate, how high the early repayment charge is, and how much you are able to over-pay. At the very least, you're going to need to do some sums! If you do choose to over-pay up to the limit, then you'd want to over-pay as much as you can at the start of the year (ie don't divide the over-payment by 12, pay it all as early as you can) to reduce interest payments. Then once you hit the limit, put the rest into a savings account: once you are out of the fixed term you can then pay the rest as a lump sum when refinancing.\"",
"title": ""
},
{
"docid": "310780",
"text": "\"I'm an American so I don't claim to know anything about Scottish tax law. But just based on what you say above: First, think about how it would work if there were no taxes. If you make a payment against the mortgage, you save 5% in interest. If you put money into a retirement account, you make whatever the profits are on the investment. If that amount comes to more than 5%, then you are better of investing in the retirement account. If it's less than 5%, you are better off paying off the mortgage. As most investments pay significantly better than 5%, this is the superior strategy. On the other hand, apparently you are paying a variable-rate mortgage, but still, mortgage rates are relatively stable. Investment returns vary all over the place and can be negative. So if you are very cautious, that's a reason to pay off the mortgage rather than invest. The younger you are, the less of a concern this should be, as in the long term, investments pretty much always recover lost ground. If you were planning to retire next year I'd have very different advice than if you are planning to retire in 30 years. But sadly, you do have to pay taxes, and that needs to be factored in. So you say that you would have to pay 25% dividend tax on any money you used to pay the mortgage. But the effective tax rate on the retirement money is 15%. So in effect money put against the mortgage pays a 25% tax, and so effectively generates only 5% * .75 = 3.75%. But money invested in the retirement plan pays only 15% tax, and so if the investment returns 3.75% / .85 = 4.4% it would give the same effective return. So if you can invest in something that gives returns of at least 4.4% per year, you're better off putting into the retirement plan than paying off the mortgage. There may be other Scottish tax implications I don't know about. As to \"\"Substantially less paperwork\"\", I have no idea how much paperwork is involved in putting money into a retirement account in Scotland. Here in the U.S., you basically call a financial management company of one sort or another and say \"\"hey, I want to open a retirement account with your company\"\", and they'll prepare most of the forms for you and you just sign them. It could be done with half an hour of your time. Of course the more you research different investment options, etc, the more time it will take. \"\"More flexible e.g. if I want to retire early\"\" If there are restrictions on when you can withdraw money from a retirement account and receive that 25% freebie you mentioned, yes, this could be a factor. Again, I don't know Scottish tax law, there may be other considerations. Here in the U.S., there's a 10% tax penalty if you withdraw money from a retirement account before the legal retirement age. Realistically that's a minor issue, if you have money in there for several years the tax benefits will be more than 10%. But yeah, it would be stupid to put money in in December and then take it out the following January and have to pay the 10% penalty. \"\"Doesn't incur the risk that the government will change the pension rules between now and when I retire\"\" Maybe. But then laws might change in your favor, too. And as you indicated that your mortgage interest rate could change, there could be risk on that side too. That all comes down to what you think the risks are all around.\"",
"title": ""
},
{
"docid": "7243",
"text": "Normally interest only mortgages are taken incase one planning to sell off the property after a few years and purchase of the property is for investment. In such a case instead of burdening oneself with a huge EMI, one opts for an interest only mortgage, and towards the end of the term, sell off the house at profit and repay back the entire principal. I am not to sure if interest only mortgages are encouraged for properties you plan to live in. Although I do not know about the ING scheme, normally there is no prepayment option on interest only mortgages, its Bank way of earning a fixed income for the contracted period and thats the reason why the interest rates are lower than a regular mortgage. If you do the math, you may be paying more in total interest than on a regular mortgage.",
"title": ""
},
{
"docid": "176415",
"text": "In your case it's all going to come down to the rates and how long you expect to live in the new house: As for whether to pay down the student loans or the mortgage first, you'll need to compare the rates, and also adjust for the tax deduction you'll get on the mortgage interest. (You make too much money to deduct any of the student loan interest.) If the student loan and morgage rates are similar, then most likely you're going to be better off paying down the student loans first. As for 15 vs 30 year, typically the rates are better on the 15 year. If they were somehow the same, then you'd be better off with the 30 yr and making the equivalent payments to the 15 year simply so you have the choice of making a lower payment in the future if you ever want to. But generally, if you plan on always making the 15 year payment amount, then you would be better off going with the 15 year just to secure the lower rate. In your case though, sticking with the 30 year and throwing the difference at the student loan may actually benefit you even more, again due to the tax deduction of mortgage interest.",
"title": ""
},
{
"docid": "141935",
"text": "\"The value of getting into the landlord business -- or any other business -- depends on circumstances at the time. How much will it cost you to buy the property? How much can you reasonably expect to collect in rent? How easy or difficult is it to find a tenant? Etc. I owned a rental property for about ten years and I lost a bundle of money on it. Things people often don't consider when calculating likely rental income are: There will be times when you have no tenant. Someone moves out and you don't always find a new tenant right away. Maintenance. There's always something that the tenant expects you to fix. Tenants aren't likely to take as good a care of the property as someone who owned it would. And while a homeowner might fix little things himself, like a broken light switch or doorknob, the tenant expects the landlord to fix such things. If you live nearby and have the time and ability to do minor maintenance, this may be no big deal. If you have to call a professional, this can get very expensive very quickly. Like for example, I once had a tenant complain that the water heater wasn't working. I called a plumber. He found that the knob on the water heater was set to \"\"low\"\". So he turned it up. He charged me, I think it was $200. I can't really complain about the charge. He had to drive to the property, figure out that that was all the problem was, turn the knob, and then verify that that really solved the problem. Tenants don't always pay the rent on time, or at all. I had several tenants who apparently saw the rent as something optional, to be paid if they had money left over that they couldn't think of anything better to do with. You may get bad tenants who destroy the place. I had one tenant who did $10,000 worth of damage. That include six inches deep of trash all over the house that had to be cleared out, rotting food all over, excrement smeared on walls, holes in the walls, and many things broken. I thought it was disgusting just to have to go in to clean it up, I can't imagine living like that, but whatever. Depending on the laws in your area, it may be very difficult to kick out a bad tenant. In my case, I had to evict two tenants, and it took about three months each time to go through the legal process. On the slip side, the big advantage to owning real estate is that once you pay it off, you own it and can continue to collect rent. And as most currencies in the world are subject to inflation, the rent you can charge will normally go up while your mortgage payments are constant.\"",
"title": ""
},
{
"docid": "234286",
"text": "\"If you are investing in a mortgage strictly to avoid taxes, the answer is \"\"pay cash now.\"\" A mortgage buys you flexibility, but at the cost of long term security, and in most cases, an overall decrease in wealth too. At a very basic level, I have to ask anyone why they would pay a bank a dollar in order to avoid paying the government 28 - 36 cents depending on your tax rate. After all, one can only deduct interest- not principal. Interest is like rent, it accrues strictly to the lender, not equity. In theory the recipient should be irrelevant. If you have a need to stiff the government, go ahead. Just realize you making a banker three times as happy. Additionally the peace of mind that comes from having a house that no banker can take away from you is, at least for me, compelling. If I have a $300,000 house with no mortgage, no payments, etc. I feel quite safe. Even if my money is tied up in equity, if a serious situation came along (say a huge doctors bill) I always have the option of a reverse mortgage later on. So, to directly counter other claims, yes, I'd rather have $300k in equity then $50k in equity and $225k in liquid assets. (Did you notice that the total net worth is $25k less? And that's even before one considers the cash flow implication of a continuing mortgage. I have no mortgage, and I'm 41. I have a lot of net worth, but the thing that I really like is that I have a roof over my head that no on e can take away from me, and sufficient savings to weather most crises). That said, a mortgage is not about total cost. It is about cash flow. To the extent that a mortgage makes your cash flow situation better, it provides a benefit- just not one that is quantifiable in dollars and cents. Rather, it is a risk/reward situation. By taking a mortgage even when you have the cash, you pay a premium (the interest rate) in order to have your funds available when you need it. A very simple strategy to calculate and/or minimize this risk would be to invest the funds in another investment. If your rate of return exceeds the interest rate minus any tax preference (e.g. 4% minus say a 25% deduction = 3%), your money is better off there, obviously. And, indeed, when interest rates are only 4%, it may may be possible to find that. That said, in most instances, a CD or an inflation protected bond or so won't give you that rate of return. There, you'd need to look at stocks- slightly more risky. When interest rates are back to normal- say 5 or 6%, it gets even harder. If you could, however, find a better return than the effective interest rate, it makes the most sense to do that investment, hold it as a hedge to pay off the mortgage (see, you get your security back if you decide not to work!), and pocket the difference. If you can't do that, your only real reason to hold the cash should be the cash flow situation.\"",
"title": ""
},
{
"docid": "147243",
"text": "\"While a lot of the answers focus on cost to replace and how much money you should have for tangible goods. There are a few more issues to consider. However before we get started, these issues are not related to ones net worth. They are related to other factors. Having money certainly helps, but someone worth only $10 may not need to insure their stuff under some circumstances. Insurance is a risk avoidance strategy. As such, it should be used to avoid risks that would otherwise cause issues for you. The normal example is a house. If you lost your house due to fire, would you be able to \"\"make it\"\" while you paid the mortgage off, and got a new mortgage to pay for a new house? This is a relatively simple view, but a good one. These days people tend to look at insurance as a savings account. I payed in X so I am entitled to Y. Heath insurance (a bit more on this later) is exacerbating the issue by selling it's self that way, but it simply isn't true. What your paying the premium for to avoid the risk of loss. Not so you can have a pool of money to draw from in time of need, but so that a time of need should never arise. Which brings us back to, should you get insurance? Tangible Assets Let's assume you have no legal or contractual obligation to have insurance. If you put the money you were spending aside would you have enough money to secure a new asset should your current one just vanish? This is the normal argument. But it has a second side. Do you need the asset at all, or can you just accept the loss. Lets pick on a red neck for a second. While certainly not millionaires, or \"\"well off\"\" by conventional means, the guy with 6 cars on bricks in his lawn does not need to insure 6 cars. If one were to vanish, it may make a hardship but hey, he's got 5 more. So with tangible goods it's more of a question of can you afford to replace the item, do you need to replace the item, and how big a risk is it to you to loose the item? What would you rather loose, the item, or the cost of the insurance? Non-tangible Assets I am going to try to keep this as un-rant like as I can manage, but be aware that I am biased. There are two big examples of non-tangible assets that are commonly insured. Life Insurance, and Health insurance. There are others, but it's very hard to get people to pay money to insure something that they don't actually have. Ideas can be insured, for example, but in order to insure an idea you have to spell it out, at that point why not just file for the patent etc. etc. Keep in mind that a lot of people and companies will insure against losses due to IP theft or other such intangible things. Largely these follow the same rules as tangible assets. This section is meant to focus on those insurances that do not. Life Insurance Life insurance is a bit odd. Were all going to die, so it seems like a \"\"good bet\"\" but what your insuring against with life insurance is an early death. For term life insurance it's a gamble. Will you die before your term runs out. For full life insurance (with no term) it's a different gamble. Will you die before you have paid in what they agreed to pay out. In many cases it's also a gamble that you will miss a payment or two and cancel the policy before you die. If the risk of your death worth the insurance. Usually while young the answer is yes. Do you leave your Family short one earner? Will they make it without the insurance? But as you get older, as life insurance becomes more of a sure thing it also becomes less needed. Your kids move out, there not dependent on you any more. You have retirement accounts setup so your partner need not worry should something happen. What risk exactly are your trying to avoid at this point. You will die. You have planned for that eventuality, it's not a risk anymore, it's a fact. Heath Insurance Is another beast all together. Historically you insured against some catastrophic event, that you couldn't really plan for. Say a heart attack. Surgery and treatment would run in the tens of thousands, so it would ruin you if you didn't have insurance to cover that. That was the risk that you were avoiding. A big, expensive event, causing financial ruin. However, over time it has shifted into something else. The general concept is still there, insure to avoid a risk. But the \"\"risk\"\" has been widened to include all manor of things that are not actually risks. For example a flu. You would go to your doctor, pay your co-pay, and your insurance would pay the rest of the visit. Then you would go to the drug store and get the drugs, pay your co-pay and the insurance pays the rest. But what risk, in this instance are you insuring against? That you can't cover the cost of a doctors visit? That you can't cover the cost of the medication? In this example, a common one, historically the \"\"mother of the house\"\" would go you have a flu, have some chicken noodle soup and go to bed. That would be the end of it. Cost of care is a day's lost wages (or maybe a weeks) and a few cans of soup. However today, because we choose to, the cost of care is much higher. We go to the doctor, pay our co-pays, the insurance has to pay it's part. The doctors office has to carry the cost of the staff it takes to see you, and the staff it takes to handle the claims with the insurance company. And now your flu, cost $1,500. But again that's not exactly true either. With heath insurance and \"\"normal\"\" medical care (like sprained ankles, and colds, etc.) the insurance only really covers the cost of having insurance. In that same flu example, if you went to the doctor as a \"\"self pay\"\" (no insurance) you would often time get a much lower, and reasonable rate. Frequently, under the cost of your standard co-pay. This seems like the doctors being \"\"bad\"\" but it's not. They don't have to file a claim, they don't have to keep track of it. They get immediate payment, not payment 6 months down the line that they need to share with other businesses. With \"\"critical\"\" or \"\"catastrophic\"\" care, heath insurance is still a good thing. If you have a big, unforeseen event, then heath insurance is great at helping you avoid that risk. With chronic (long term) care, your back in the same boat as the flu. Often times you can get better, and cheaper, care as a self pay patent, then as a insured patent. That is not always the case however. So you have to measure your own circumstance, and decide if insurance is right for you. But remember insurance is about risk avoidance, and not about paying less. You will ALWAYS pay more for insurance. It's designed that way. Even if the cost is hidden in many ways. (Taxes, spread out over visits, or prescriptions, etc.)\"",
"title": ""
},
{
"docid": "98294",
"text": "Pay off the Highest interest loan rate first. You must be doing something funky with how long your terms are... If you give a bit more info about your loan's such as the term and how much extra you have right now to spend it could be explained in detail why that would be the better choice using your numbers. You have to make sure when you are analyzing your different loan options that you make sure you are comparing apples to apples. IE make sure that you are either comparing the present value, future value or amortization payments... EDIT: using some of your numbers lets say you have 5000 dollars in your pocket you have 3 options. excel makes these calculations easier... Do nothing: in 80 months your Student Loan will be payed in full and you will have 54676.08 owing on your mortgage and 5000 in your pocket(assuming no bank interest) for mortgage: Pay off Student loan and allocate Student loans amortization to Mortgage: in 80 months you will have $47,910.65 owing on mortgage and student loan will be paid in full For mortgage: Pay 5000 on Mortgage: in 80 months student loan will be paid in full and you will have $48,204.92 owing on mortgage For mortgage:",
"title": ""
},
{
"docid": "298776",
"text": "Similar to what Adam F says above, except instead of just transfering the amount you spend on the credit card into the high interest account, why not keep the majority of your funds (apart from a small amount, say a couple of hundred for emergencies) in the high interest account until the credit card needs to be paid off. Even better, if you have a mortgage with an 100% offset account keep all your funds in this, and pay off your credit card in full from it on or before the due date. Being a 100% offset to your mortgage interest rate you will be saving at a higher rate than a high interest rate savings account, and you will be able to do all your normal banking from it unlike a high interest account which you usually have to link to an additional account to deposit and withdrawl money to and from. If you are to use a credit card keep these simple rules in mind: Hope this has helped, Regards Victor",
"title": ""
},
{
"docid": "194382",
"text": "Use the $11k to pay down either car loan (your choice). You should be able to clear one loan very quickly after that lump sum. After that, continue to aggressively pay down the other car loan until it is clear. Lastly, pay off the mortgage while making sure you are financially stable in other areas (cash-on-hand, retirement, etc) Reasoning: The car loans are very close in value, making it a wash as far as payoff speed. The 2.54% interest is not a large factor here. As a percentage of all these numbers, the few bucks a month isn't going to change your financial situation. This is assuming you will pay off both loans well ahead of schedule, making the interest rate negligible in the answer. Paying off the mortgage last is due to the risk associated with the car loans. The cars are guaranteed to lose value at an alarming rate. While a house certainly may lose value, it is far from an expectation. It is likely that your house will maintain and/or increase in value, unless you have specific circumstances not disclosed here. This makes the mortgage a lower risk loan in your financial world. You can probably sell the house to clear the loan balance if necessary. The cars are far more likely to depreciate beyond the loan balance.",
"title": ""
},
{
"docid": "9390",
"text": "\"Residential mortgages normally explicitly state that the property cannot be let without explicit permission, whereas BTL mortgages typically require that the property be let. There are other differences. Residential mortgages are regulated, which means that consumers have a degree of protection from mis-selling; most BTLs are not, as landlords are expected to know what they're doing. Affordability of residential mortgages are based on your income, since that is how you are going to pay for them. BTLs are (mostly) assessed based on the property's rental income, since it's that that will fund the mortgage. Finally, residential mortgages are typically done on a repayment basis, so that at the end of the term, you've paid off the entire loan, whereas BTLs are typically interest-only, on the assumption that you'll either sell the property, or remortgage, at the end of the term. (I've used words like \"\"typically\"\" a lot to give an overall picture of the differences. Obviously it's a bit more complicated than that, and there are exceptions to a lot of the above descriptions.)\"",
"title": ""
},
{
"docid": "386994",
"text": "The main reason for paying your mortgage off quickly is to reduce risk should a crisis happen. If you don't have a house payment, you have much higher cash flow every month, and your day-to-day living expenses are much lower, so if an illness or job loss happens, you'll be in a much better position to handle it. You should have a good emergency fund in place before throwing extra money at the mortgage so that you can cover the bigger surprises that come along. There is the argument that paying off your mortgage ties up cash that could be used for other things, but you need to be honest with yourself: would you really invest that money at a high enough rate of return to make up your mortgage interest rate after taxes? Or would you spend it on other things? If you do invest it, how certain are you of that rate of return? Paying off the mortgage saves you your mortgage interest rate guaranteed. Finally, there is the more intangible aspect of what it feels like to be completely debt free with no payments whatsoever. That feeling can be a game-changer for people, and it can free you up to do things that you could never do when you're saddled with a mortgage payment every month.",
"title": ""
},
{
"docid": "391819",
"text": "Besides the reason in @rhaskett's answer, it is important to consider that paying off a 30-year mortgage as if it was a 15-year is much more inconvenient than just paying the regular payments of a 15-year mortgage. When you pay extra on your mortgage, some lenders do not know what to do with the extra payment, and need to be told explicitly that the extra needs to be applied toward the principal. You might need to do this every month with every payment. In addition, some lenders won't allow you to set up an automatic payment for more than the mortgage payment, so you might need to explicitly submit your payment with instructions for the lender each month, and then follow up each month to make sure that your payment was credited properly. Some lenders are better about this type of thing than others, and you won't really know how much of a hassle it will be with your lender until you start making payments. If you intend to pay it off in 15 years, then just get the 15-year mortgage.",
"title": ""
},
{
"docid": "543365",
"text": "\"In most cases of purchases the general advice is to save the money and then make the purchase. Paying cash for a car is recommended over paying credit for example. For a house, getting a mortgage is recommended. Says who? These rules of thumb hide the actual equations behind them; they should be understood as heuristics, not as the word of god. The Basics The basic idea is, if you pay for something upfront, you pay some fixed cost, call it X, where as with a loan you need to pay interest payments on X, say %I, as well as at least fixed payments P at timeframe T, resulting in some long term payment IX. Your Assumption To some, this obviously means upfront payments are better than interest payments, as by the time the loan is paid off, you will have paid more than X. This is a good rule of thumb (like Newtonian's equations) at low X, high %I, and moderate T, because all of that serves to make the end result IX > X. Counter Examples Are there circumstances where the opposite is true? Here's a simple but contrived one: you don't pay the full timeframe. Suppose you die, declare bankruptcy, move to another country, or any other event that reduces T in such a way that XI is less than X. This actually is a big concern for older debtors or those who contract terminal illnesses, as you can't squeeze those payments out of the dead. This is basically manipulating the whole concept. Let's try a less contrived example: suppose you can get a return higher than %I. I can currently get a loan at around %3 due to good credit, but index funds in the long run tend to pay %4-%5. Taking a loan and investing it may pay off, and would be better than waiting to have the money, even in some less than ideal markets. This is basically manipulating T to deal with IX. Even less contrived and very real world, suppose you know your cash flow will increase soon; a promotion, an inheritance, a good market return. It may be better to take the loan now, enjoy whatever product you get until that cash flows in, then pay it all off at once; the enjoyment of the product will make the slight additional interest worth it. This isn't so much manipulating any part of the equation, it's just you have different goals than the loan. Home Loan Analysis For long term mortgages, X is high, usually higher than a few years pay; it would be a large burden to save that money for most people. %I is also typically fairly low; P is directly related to %I, and the bank can't afford to raise payments too much, or people will rent instead, meaning P needs to be affordable. This does not apply in very expensive areas, which is why cities are often mostly renters. T is also extremely long; usually mortgages are for 15 or 30 years, though 10 year options are available. Even with these shorter terms, it's basically the longest term loan a human will ever take. This long term means there is plenty of time for the market to have a fluctuation and raise the investments current price above the remainder of the loan and interest accrued, allowing you to sell at a profit. As well, consider the opportunity cost; while saving money for a home, you still need a place to live. This additional cost is comparable to mortgage payments, meaning X has a hidden constant; the cost of renting. Often X + R > IX, making taking a loan a better choice than saving up. Conclusion \"\"The general advice\"\" is a good heuristic for most common human payments; we have relatively long life spans compared to most common payments, and the opportunity cost of not having most goods is relatively low. However, certain things have a high opportunity cost; if you can't talk to HR, you can't apply for jobs (phone), if you can't get to work, you can't eat (car), and if you have no where to live, it's hard to keep a job (house). For things with high opportunity costs, the interest payments are more than worth it.\"",
"title": ""
},
{
"docid": "274108",
"text": "Can I pay $12,000 extra once a year or $1000 every month - which option is better? Depends when. If you mean 12K now vs 1K a month over the next 12 months, repeating this each year, now wins. If you mean saving 1K a month for 12 months then doing a lumpsum, the 1K a month wins. Basically, a sooner payment saves you more money than a later payment. The first option does sound better, but for a 30 year mortgage, is it that significant? Your number one issue is that you have a thirty year mortgage. The interest you pay on it is monstrous. For the 30 year term, you pay around 500K in interest. A 15-year mortgage is 300K cheaper (only 200K in interest will be paid). The monthly payment would be 1250 more. How much money and years on a mortgage can I save? When is the best time to pay? At the end of each year? You can knock off about a dozen years. Save I think ~250K. You can find mortgage calculators online or talk to your mortgage advisor to play around with the numbers.",
"title": ""
},
{
"docid": "155358",
"text": "You would have to find someone in the other state who wanted to swap. This is conceivable but difficult if you want the houses to be the same value. How do you find the one person who lives in the right place now and wants to move to the right area? The normal way this situation is handled is to simply put your house on the market. At the same time, you find a new house in the new location. You arrange for a new mortgage for the new house and make purchase contingent on selling the old house. Your buyer pays off your mortgage and gives you a bit left over that you use as a downpayment on the new house. Note that you take a loss on closing costs when you do this. This is why if you are in the position where you move frequently, you may be better off renting. Sometimes an employer will help with this, paying for a long term hotel or short term rental. This can give you more room to sell and buy the houses. If you have to move right now, immediately, not in a few months when your housing situation is fixed, consider double renting. You rent out your mortgaged house to someone and pay rent on a new place. You may put some of your stuff in storage until you get into your permanent place. The downside is that it can be harder to sell a house with a tenant until you are close to the end of the lease. And of course, you are probably not in the best position to get or pay good rent. Your situation restricts your options. You might get stuck in this situation for a year so as to get the time that you need to line up a buyer. Of course, you may get lucky and find someone who wants your old house as an investment property. Such a person won't be bothered by a tenant. But they usually want a good price. After all, they want to make money off it. There are those operations that advertise that they buy ugly houses. They want a good deal. You'll probably take a bath. But they can buy quickly, so you can move on quickly. No waiting until they find a buyer. And I'm not saying that you can't do a swap like you want. I'm just saying that you may find it difficult to find a swapping partner. Perhaps an investment person would be up for it. They take your house in trade for their house, letting you stay in their house until they can fix up your old house and either rent it or sell it. The problem is that it may be hard to find such an investor who can handle a house where you are and has a house where you need to be. I don't have a good suggestion for finding a swapping partner other than calling a lot of realtors and asking for suggestions. Maybe a bit of online checking for properties where the owner's business is managing the sale.",
"title": ""
}
] |
7760
|
What is the best strategy for after hours trading?
|
[
{
"docid": "16806",
"text": "I would never trade after hours and I have 30 years of trading experience. It is a very volatile emotion driven market without a lot of the big players that arbitrage wrong pricing. If I were you I would simply use limit orders you input while the market is closed. If you want to get kute you can put in low-ball offers (and vice versa) to see if they get filled in the volatility at market open. Then check in (when?) when you wake up (or before you go to bed, etc) and revise the limit if not filled. In other words don't 'trade'. Know what your company is worth and put in orders that reflect that.",
"title": ""
},
{
"docid": "240744",
"text": "First you will need a plan stating three main points: You will have to decide what criteria you will use to answer these points. You might use Fundamental Analysis to find what to buy and Technical Analysis to decide when to buy and when to sell (your buy and sell triggers). Once you have a Trading Plan in place you would need to find a broker with conditional orders. You can place conditional buy orders to get in a trade (for example if the price moves above or below a target price). You can place conditional stop loss orders if your trade goes against you, and you can also place conditional profit target stops to automatically get out if rises to your desired profit target. You can place one, two or many conditional orders after hours which will enable you to trade without being in front of your screen all day long.",
"title": ""
}
] |
[
{
"docid": "396657",
"text": "The study of technical analysis is generally used (sometimes successfully) to time the markets. There are many aspects to technical analysis, but the simplest form is to look for uptrends and downtrends in the charts. Generally higher highs and higher lows is considered an uptrend. And lower lows and lower highs is considered a downtrend. A trend follower would go with the trend, for example see a dip to the trend-line and buy on the rebound. A simple strategy for this is shown in the chart below: I would be buying this stock when the price hits or gets very close to the trendline and then it bounces back above it. I would then have sold this stock once it has broken through below the trendline. This may also be an appropriate time if you were looking to short this stock. Other indicators could also be used in combination for additional confirmation of what is happening to the price. Another type of trader is called a bottom fisher. A bottom fisher would wait until a break above the downtrend line (second chart) and buy after confirmation of a higher high and possibly a higher low (as this could be the start of a new uptrend). There are many more strategies dealing with the study of technical analysis, and if you are interested you would need to find and learn about ones that suit your investment styles, whether you prefer short term trading or longer term investing, and your appetite for risk. You can develop strategies using various indicators and then paper trade or backtest these strategies. You can also manually backtest a strategy in most charting packages. You can go back in time on the chart so that the right side of the chart shows a date in the past (say one year ago or 10 years ago), then you can click forward one day at a time (or one week at a time if using weekly charts). With your indicators on the chart you can do virtual trades to buy or sell whenever a signal is given as you move forward in time. This way you may be able to check years of data in a day to see if your strategy works. Whatever you do, you need to document your strategies in writing in a written trading or investment plan together with a risk management strategy. You should always follow the rules in your written plan to avoid you making decisions based on emotions. By backtesting or paper trading your strategies it will give you confidence that they will work over the long term. There is a lot of work involved at the start, but once you have developed a documented strategy that has been thoroughly backtested, it will take you minimal time to successfully manage your investments. In my shorter term trading (positions held from a couple of days to a few weeks) I spend about half an hour per night to manage my trades and am up about 50% over the last 7 months. For my longer term investing (positions held from months to years) I spend about an hour per week and have been averaging over 25% over the last 4 years. Technical Analysis does work for those who have a documented plan, have approached it in a systematic way and use risk management to protect their existing and future capital. Most people who say that is doesn't work either have not used it themselves or have used it ad-hock without putting in the initial time and work to develop a documented and systematic approach to their trading or investing.",
"title": ""
},
{
"docid": "220110",
"text": "Very common question. There is no any rule of thumb. This solely depends on your trading strategy. I will share my own experience. My day starts with the daily chart, if I have a signal, either I open my position or I check 30 minute chart to make sure that it won't go too much against my trade. and I open my position. If I am waiting for the signal the minimum timeframe is 4 hours for me. I use 30 minutes to find the best time to enter the market. So, this is totally something special for my trading strategy, that is why those things can change based on the different strategies. I also check weekly and monthly charts to confirm trend. I have been busy with forex since 2007 and I am a verified investor on etoro At the end, I never use 1,5,15,60 minute charts as they are against my strategy.",
"title": ""
},
{
"docid": "118712",
"text": "In general a stock can open at absolutely any price with no regard for the closing price or after hours price the previous day. The opening price will be determined by the best bid and offer made by people who decide to trade the next day. Some of the those people may have put orders in on a prior day that are still on the books and matter, but there's a lot of time overnight for people to cancel orders and enter new ones, which is especially likely to happen if there was substantive news overnight. As for what you can do in your case, you have the same options that you always had: Sell or hold. If you're selling, you can sell after hours, in the pre-open hours, or during the trading day. There's nothing we can say about this case that's really any different than we can say about any other stock on any other day.",
"title": ""
},
{
"docid": "361163",
"text": "The sentiment is because between closing and opening a lot can happen, and between opening and the time your order actually goes through, even more can happen. An after-hours trade has an extra amount of short-term risk attached; the price of a stock at the opening bell is technically the same as its price as of the closing the previous trading day, but within a tenth of a second, which is forever in a computerized exchange, that price may move drastically one way or the other, based on news and on other markets. The sentiment, therefore, is simple; if you're trading after-hours, you're trading risky. You're not trading based on what the market's actually doing, you're trading based on what you think the market will do in the morning, and there's still more math going on every second in the privately-held supercomputers in rented cubes in the NYSE basement than you could do all night, digesting this news and projecting what it's going to do to the stocks. Now, if you've done your homework and the stock looks like a good long-term buy, with or without any after-hours news, then place the order at 3 in the morning; who cares what the stock's gonna do at the opening bell. You're gonna hold that stock for the next ten years, maybe; what it does in 5 seconds of opening turmoil is relatively minor compared to the monthly trends that you should be worrying about.",
"title": ""
},
{
"docid": "532599",
"text": "The two answers so far are right, but there's a third factor - for many stocks, there's after hours trading. So the official 4PM close is not what the stock's last trade was when they open again. Regardless, even that after hour price is not the starting point as Muro points out.",
"title": ""
},
{
"docid": "255396",
"text": "Unless you have a lot of money to get rid of you should spend at least a year trading with a dummy account. It takes a long time to work out what is gong on and your training will get very expensive if you start using real money. Don't start trading with real money until you : Have a strategy. Never trade on a whim. Only trade if your strategy says it is time to trade. Are able to stick to that strategy. It is amazing how easy it is to stray from your strategy just because you feel it is right or you have to try to make up some losses. You will lose money doing this. You are making significant profits for at least 6 months using 1. and 2. with your dummy account. Even after all this, you will probably still lose money. Make sure you only trade with money you can afford to lose. ie. Never trade with this months rent money.",
"title": ""
},
{
"docid": "467463",
"text": "Typically the settlement price for a financial instrument (such as AAPL stock) underlying a derivative contract is determined from the average price of trading in that instrument during some short time window specified by the exchange offering the derivative. (Read the fine print on your contract to learn the exact date and time of that settlement period.) Because it's in an exchange's best interest to appear as fair as possible, the exchange will in general pick a high-volume period of time -- such as the close of trading on the expiry date -- in which to determine the settlement price. Now, the expiry date/time may be different from the last time at which the option can be traded, which may be different from the underlying settlement time. For example, most US equity options currently expire on the Saturday following the third Friday of the month, whereas they can last be traded at end-of-day on the third Friday of the month, and the settlement period may be at a slightly different time on the third Friday of the month. (Again, read the contract to know for sure.) Moreover, your broker may demand to know whether you plan to exercise the option at an even earlier date/time. So, to answer your question: After-hours trading can only affect the settlement price of an underlying instrument if the exchange in question decides that the settlement period should happen during after-hours trading. But since no exchange that wants to stay in business would possibly do that, the answer is no. Contract expiry time, contract exercise time, final contract trading time, and underlying settlement time may all fall at different dates/times. The important one for your question is settlement time.",
"title": ""
},
{
"docid": "131117",
"text": "Disclaimer: I don't work in the finance industry, and simply took a few classes in corporate finance and management during my undergrad. It depends on what type of investing you're talking about. If you're talking about building a portfolio of securities, then CAPM is the basis for most valuation models. Generally, CAPM will have you discount based on your best available risk-free rate (usually t-bills or some other fixed income source with a reliable backer). Even after your valuation, the basic theory of risk management for an investment portfolio is still to maintain a diverse basket of poorly correlated products. If you're talking about corporate finance where a firm is considering an investment such as a new project, then a determining a WACC and using it as a discount rate for your cash flow is a basic strategy. This is a basic strategy, but there are better ones depending on the specifics of the investment. This is where evaluating exposures is important. To hedge counterparty risk, you might discount by the estimated probability of non-payment or buy trade insurance. To hedge currency risk, you might buy forwards, options, or look into a money market hedge. To hedge political risks like repatriation or changes in tax laws or regulation you might buy political risk insurance. To hedge exposure to a particular commodity price, you can trade futures.",
"title": ""
},
{
"docid": "576632",
"text": "\"If I really understood it, you bet that a quote/currency/stock market/anything will rise or fall within a period of time. So, what is the relationship with trading ? I see no trading at all since I don't buy or sell quotes. You are not betting as in \"\"betting on the outcome of an horse race\"\" where the money of the participants is redistributed to the winners of the bet. You are betting on the price movement of a security. To do that you have to buy/sell the option that will give you the profit or the loss. In your case, you would be buying or selling an option, which is a financial contract. That's trading. Then, since anyone should have the same technic (call when a currency rises and put when it falls)[...] How can you know what will be the future rate of exchange of currencies? It's not because the price went up for the last minutes/hours/days/months/years that it will continue like that. Because of that everyone won't have the same strategy. Also, not everyone is using currencies to speculate, there are firms with real needs that affect the market too, like importers and exporters, they will use financial products to protect themselves from Forex rates, not to make profits from them. [...] how the brokers (websites) can make money ? The broker (or bank) will either: I'm really afraid to bet because I think that they can bankrupt at any time! Are my fears correct ? There is always a probability that a company can go bankrupt. But that's can be very low probability. Brokers are usually not taking risks and are just being intermediaries in financial transactions (but sometime their computer systems have troubles.....), thanks to that, they are not likely to go bankrupt you after you buy your option. Also, they are regulated to insure that they are solid. Last thing, if you fear losing money, don't trade. If you do trade, only play with money you can afford to lose as you are likely to lose some (maybe all) money in the process.\"",
"title": ""
},
{
"docid": "241059",
"text": "\"NASDAQ has Pre and After market : NASDAQ Trading Schedule Regular Trading Session Schedule The NASDAQ Stock Market Trading Sessions (Eastern Time) Pre-Market Trading Hours from 4:00 a.m. to 9:30 a.m. Market Hours from 9:30 a.m. to 4:00 p.m. After-Market Hours from 4:00 p.m. to 8:00 p.m. Quote and order-entry from 4:00 a.m. to 8:00 p.m. Quotes are open and firm from 4:00 a.m. to 8:00 p.m. You can trade in Pre/After Market but liquidity is very low. If an \"\"unexpected world events\"\" occurs, the volume/liquidity will most certainly increase. Another example is the Forex Market that's open 24/7 around the world. As one major forex market closes, another one opens. According to GMT, for instance, forex trading hours move around the world like this: available in New York between 01:00 pm – 10:00 pm GMT; at 10:00 pm GMT Sydney comes online; Tokyo opens at 00:00 am and closes at 9:00 am GMT; and to complete the loop, London opens at 8:00 am and closes at 05:00 pm GMT. This enables traders and brokers worldwide, together with the participation of the central banks from all continents, to trade online 24 hours a day. src\"",
"title": ""
},
{
"docid": "106817",
"text": "1. It is difficult. There is no formal process outside of undergrad and MBA programs to easily gain access to interviews. At your level, its mostly about connections. If willing to start near bottom, go to your business school and start applying to bank associate programs. Sounds like you would like sales and trading more than M&A, so focus there. 2. If you got in at associate level, you would do 1-3 months of training and then get assigned a desk. Finance going through a tough time right now, so trajectory isn't what it used to be. Expect to be a VP after 2-4 years, then its all dependent on luck and skill. 3. If you land a job at a top 15 bank, you should be making total comp of 150k or more after the first year. Salaries not quite at 150k, but most VPS make over 150k salary, not to mention bigger bonus's. 4. If you did M&A you would be working very serious hours. If you go into Sales and Trading your hours will be anywhere from 40 to 60 hours a week depending on the desk. Trading hours tend to be the shortest. 5. Boston isn't a hot bed for i-banking finance. NYC, London, Sing, Hong Kong tend to be the places to be. I know nobody in Boston that could help.",
"title": ""
},
{
"docid": "360059",
"text": "\"There are people (well, companies) who make money doing roughly what you describe, but not exactly. They're called \"\"market makers\"\". Their value for X% is somewhere on the scale of 1% (that is to say: a scale at which almost everything is \"\"volatile\"\"), but they use leverage, shorting and hedging to complicate things to the point where it's nothing like a simple as making a 1% profit every time they trade. Their actions tend to reduce volatility and increase liquidity. The reason you can't do this is that you don't have enough capital to do what market makers do, and you don't receive any advantages that the exchange might offer to official market makers in return for them contracting to always make both buy bids and sell offers (at different prices, hence the \"\"bid-offer spread\"\"). They have to be able to cover large short-term losses on individual stocks, but when the stock doesn't move too much they do make profits from the spread. The reason you can't just buy a lot of volatile stocks \"\"assuming I don't make too many poor choices\"\", is that the reason the stocks are volatile is that nobody knows which ones are the good choices and which ones are the poor choices. So if you buy volatile stocks then you will buy a bunch of losers, so what's your strategy for ensuring there aren't \"\"too many\"\"? Supposing that you're going to hold 10 stocks, with 10% of your money in each, what do you do the first time all 10 of them fall the day after you bought them? Or maybe not all 10, but suppose 75% of your holdings give no impression that they're going to hit your target any time soon. Do you just sit tight and stop trading until one of them hits your X% target (in which case you start to look a little bit more like a long-term investor after all), or are you tempted to change your strategy as the months and years roll by? If you will eventually sell things at a loss to make cash available for new trades, then you cannot assess your strategy \"\"as if\"\" you always make an X% gain, since that isn't true. If you don't ever sell at a loss, then you'll inevitably sometimes have no cash to trade with through picking losers. The big practical question then is when that state of affairs persists, for how long, and whether it's in force when you want to spend the money on something other than investing. So sure, if you used a short-term time machine to know in advance which volatile stocks are the good ones today, then it would be more profitable to day-trade those than it would be to invest for the long term. Investing on the assumption that you'll only pick short-term winners is basically the same as assuming you have that time machine ;-) There are various strategies for analysing the market and trying to find ways to more modestly do what market makers do, which is to take profit from the inherent volatility of the market. The simple strategy you describe isn't complete and cannot be assessed since you don't say how to decide what to buy, but the selling strategy \"\"sell as soon as I've made X% but not otherwise\"\" can certainly be improved. If you're keen you can test a give strategy for yourself using historical share price data (or current share price data: run an imaginary account and see how you're doing in 12 months). When using historical data you have to be realistic about how you'd choose what stocks to buy each day, or else you're just cheating at solitaire. When using current data you have to beware that there might not be a major market slump in the next 12 months, in which case you won't know how your strategy performs under conditions that it inevitably will meet eventually if you run it for real. You also have to be sure in either case to factor in the transaction costs you'd be paying, and the fact that you're buying at the offer price and selling at the bid price, you can't trade at the headline mid-market price. Finally, you have to consider that to do pure technical analysis as an individual, you are in effect competing against a bank that's camped on top of the exchange to get fastest possible access to trade, it has a supercomputer and a team of whizz-kids, and it's trying to find and extract the same opportunities you are. This is not to say the plucky underdog can't do well, but there are systematic reasons not to just assume you will. So folks investing for their retirement generally prefer a low-risk strategy that plays the averages and settles for taking long-term trends.\"",
"title": ""
},
{
"docid": "251300",
"text": "The answer is to your question is somewhat complicated. You will be unable to compete with the firms traditionally associated with High Frequency Trading in any of their strategies. Most of these strategies which involve marketing making, latency arbitrage, and rebate collection. The amount of engineering required to build the infrastructure required to run this at scale makes it something which can only be undertaken by a team of highly skilled engineers. Indeed, the advantage of firms competing in this space such as TradeBot, TradeWorx, and Getco comes from this infrastructure as most of the strategies that are developed are necessarily simple due to the latency requirements. Now if you expand the definition of HFT to include all computerized automated trading you most certainly can build strategies that are profitable. It is not something that you probably want to tackle on your own but I know of a couple of people that did go it alone successfully for a couple of years before joining an established firm to run a book for them. In order to be successful you will most likely need to develop a unique strategies. The good news is because that you are trying to deploy a very tiny amount of capital you can engage in trades that larger firms would not because the strategies cannot hold enough capital relative to the firms capital base. I am the co-founder of a small trading firm that successfully trades the US Equities and Equity Derivatives markets. A couple of things to note is that if you want to do this you should consider building a real business. Having some more smart brains around you will help. You don't need exchange colocation for all strategies. Many firms, including ours, colocate in a data center that simply has proximity to the exchanges data centers. You will need to keep things simple to be effective. Don't except all the group think that this is impossible. It is possible although as a single individual it will be more difficult. It will require long, long hours as you climb the algorithmic trading learning curve. Good luck.",
"title": ""
},
{
"docid": "414036",
"text": "\"During market hours, there are a lot of dealers offering to buy and sell all exchange traded stocks. Dealers don't actually care about the company's fundamentals and they set their prices purely based on order flow. If more people start to buy than sell, the dealer notices his inventory going down and starts upping the price (both his bid and ask). There are also traders who may not be \"\"dealers\"\", but are willing to sell if the price goes high enough or buy if the price goes low enough. This keeps the prices humming along smoothly. During normal trading hours, if you buy something and turn around and sell it two minutes later, you'll probably be losing a couple cents per share. Outside normal market hours, the dealers who continue to have a bid and ask listed know that they don't have access to good price information -- there isn't a liquid market of continuous buying and selling for the dealer to set prices he considers safe. So what does he do? He widens the spread. He doesn't know what the market will open tomorrow at and doesn't know if he'll be able to react quickly to news. So instead of bidding $34.48 and offering at $34.52, he'll move that out to $33 and $36. The dealer still makes money sometimes off this because maybe some trader realized that he has options expiring tomorrow, or a short position that he's going to get a margin call on, or some kind of event that pretty much forces him to trade. Or maybe he's just panicking and overreacting to some news. So why not trade after hours? Because there's no liquidity, and trading when there's no liquidity costs you a lot.\"",
"title": ""
},
{
"docid": "177424",
"text": "\"No, a jump in market capitalization does not equal the amount that has been invested. Market cap is simply the stock price times the total number of shares. This represents a theoretical value of the company. I say \"\"theoretical\"\" because the company might not be able to be sold for that at all. The quoted stock price is simply what the last buyer and seller of stock agreed upon for the price of their trade. They really only represent themselves; other investors may decide that the stock is worth more or less than that. The stock price can move on very little volume. In this case, Amazon had released a very good earnings report after the bell yesterday, and the price jumped in after hours trading. The stock price is up, but that simply means that the few shares traded overnight sold for much higher than the closing price yesterday. After the market opens today and many more shares are traded, we'll get a better idea what large numbers of investors feel about the price. But no matter what the price does, the change in market cap does not equal the amount of new money being invested in the company. Market cap is the price of the most recent trades extrapolated out across all the shares.\"",
"title": ""
},
{
"docid": "481298",
"text": "Stop orders and stop limit orders typically do not execute during extended hours after the general market session has closed. Stop orders are market orders and market orders especially are not executed during extended hours. Although there are exceptions because a broker can say one thing and do another thing with the way order types are presented to customers vs what their programming actually does. The regulatory burden is a slap on the wrist, so you need to ask the broker what their practices are. Orders created during normal market hours do not execute in extended sessions, different orders would have to be made during the extended session. Your stop order should execute if the normal market hour price stays below your stop price. So a stop limit would actually be worse here, because a stop limit will create a limit order which may never get hit (since it is above the best bid best ask)",
"title": ""
},
{
"docid": "498014",
"text": "It looks like GOOG did not have a pre-market trade until 7:14 am ET, so Google Finance was still reporting the last trade it had, which was in the after-hours session yesterday. FB, on the other hand, was trading like crazy after-hours yesterday and pre-market today as it had an earnings report yesterday.",
"title": ""
},
{
"docid": "355548",
"text": "As a futures trader, I can tell you that the highs and lows for the ES futures diverge simply because they trade around the clock, from 6PM ET to 5PM ET the next day. The SPX is only open during market hours, as is the SPY, but the SPY also trades in the extended hours sessions for about 3.5 hours before and after the regular hours of 930 AM ET to 4PM ET ET. So bottom line, while they pretty much track each other, the difference in their trading hours results in the highs and lows being different.",
"title": ""
},
{
"docid": "265365",
"text": "There are several reasons it is not recommended to trade stocks pre- or post-market, meaning outside of RTH (regular trading hours). Since your question is not very detailed I have to assume you trade with a time horizon of at least more than a day, meaning you do not trade intra-day. If this is true, all of the above points are a non-issue for you and a different set of points becomes important. As a general rule, using (3) is the safest regardless of what and how you trade because you get price guarantee in trade for execution guarantee. In the case of mid to longer term trading (1 week+) any of those points is viable, depending on how you want to do things, what your style is and what is the most comfortable for you. A few remarks though: (2) are market orders, so if the open is quite the ride and you are in the back of the execution queue, you can get significant slippage. (1) may require (live) data of the post-market session, which is often not easy to come by for the entire US stock universe. Depending on your physical execution method (phone, fax, online), you may lack accurate information of the post-market. If you want to execute orders based on RTH and only want to do that after hours because of personal schedule constraints, this is not really important. Personally I would always recommend (3), independent of the use case because it allows you more control over your orders and their fills. TL;DR: If you are trading long-term it does not really matter. If you go down to the intra-day level of holding time, it becomes relevant.",
"title": ""
},
{
"docid": "57520",
"text": "Pre-Market trading activity is shown on the site from 4:15 - 9:30 AM (actual trading starts at 4:00 AM EST) The NASDAQ Stock Market Trading Sessions (Eastern Time) Pre-Market Trading Hours from 4:00 a.m. to 9:30 a.m. Market Hours from 9:30 a.m. to 4:00 p.m. After-Market Hours from 4:00 p.m. to 8:00 p.m. Read more: http://www.nasdaq.com/about/trading-schedule.aspx#ixzz38OtcISrq In this case GOOG did not trade in the Pre-market until that time and FB was.",
"title": ""
},
{
"docid": "378889",
"text": "\"Often these types of trades fall into two different categories. An error by broker or exchange. Exchange clearing out part of their books incorrectly is an example. Most exchanges make firms reopen their positions for after market hours. There may have been an issue doing so or exchange could incorrectly cancel positions. I was in the direct feed industry for years and this was a big issue. At the same time the broker can issue a no limit buy on accident (or has software that is prospecting and said software has a bug or written poorly). unscrupulous parties looking to feign an upswing or downswing in market. Let's say you hold 500k shares in a stock that sells for $11. You could possibly buy 100 shares for $13. Trust me you will find a seller. Then you are hoping that people see that trade as a \"\"norm\"\" and trade from there, allowing you to rake in $1M for spending an extra $200 - NOTE this is not normal and an extreme example. This was so common in the early days of NASDAQ after hours that they discontinued using the after hours trades as part of historical information that they keep like daily/yearly high or closing price. The liquidity allows for manipulation. It isn't seen as much now since this has been done a million times but it does still happen.\"",
"title": ""
},
{
"docid": "515579",
"text": "If I understand you correctly, you are noticing that a stock's price can change drastically when the time changes from pre-market trading hours to open market hours. This could occur because a much smaller pool of investors make trades during pre-market and after-market hours. When the regular market opens there is a large influx of trades, causing the prices to jump.",
"title": ""
},
{
"docid": "176883",
"text": "\"A 'Call' gives you the right, but not the obligation, to buy a stock at a particular price. The price, called the \"\"strike price\"\" is fixed when you buy the option. Let's run through an example - AAPL trades @ $259. You think it's going up over the next year, and you decide to buy the $280 Jan11 call for $12. Here are the details of this trade. Your cost is $1200 as options are traded on 100 shares each. You start to have the potential to make money only as Apple rises above $280 and the option trades \"\"in the money.\"\" It would take a move to $292 for you to break even, but after that, you are making $100 for each dollar it goes higher. At $300, your $1200 would be worth $2000, for example. A 16% move on the stock and a 67% increase on your money. On the other hand, if the stock doesn't rise enough by January 2011, you lose it all. A couple points here - American options are traded at any time. If the stock goes up next week, your $1200 may be worth $1500 and you can sell. If the option is not \"\"in the money\"\" its value is pure time value. There have been claims made that most options expire worthless. This of course is nonsense, you can see there will always be options with a strike below the price of the stock at expiration and those options are \"\"in the money.\"\" Of course, we don't know what those options were traded at. On the other end of this trade is the option seller. If he owns Apple, the sale is called a \"\"covered call\"\" and he is basically saying he's ok if the stock goes up enough that the buyer will get his shares for that price. For him, he knows that he'll get $292 (the $280, plus the option sale of $12) for a stock that is only $259 today. If the stock stays under $280, he just pocketed $12, 4.6% of the stock value, in just 3 months. This is why call writing can be a decent strategy for some investors. Especially if the market goes down, you can think of it as the investor lowering his cost by that $12. This particular strategy works best in a flat to down market. Of course in a fast rising market, the seller misses out on potentially high gains. (I'll call it quits here, just to say a Put is the mirror image, you have the right to sell a stock at a given price. It's the difference similar to shorting a stock as opposed to buying it.) If you have a follow up question - happy to help. EDIT - Apple closed on Jan 21, 2011 at $326.72, the $280 call would have been worth $46.72 vs the purchase price of $12. Nearly 4X return (A 289% gain) in just over 4 months for a stock move of 26%. This is the leverage you can have with options. Any stock could just as easily trade flat to down, and the entire option premium, lost.\"",
"title": ""
},
{
"docid": "69395",
"text": "\"Your plan already answers your own question in the best possible way: If you want to be able to make the most possible profit from a large downward move in a stock (in this case, a stock that tracks gold), with a limited, defined risk if there is an upward move, the optimal strategy is to buy a put option. There are a few Exchange Traded Funds (ETFs) that track the price of gold. think of them as stocks that behave like gold, essentially. Two good examples that have options are GLD and IAU. (When you talk about gold, you'll hear a lot about futures. Forget them, for now. They do the same essential thing for your purposes, but introduce more complexity than you need.) The way to profit from a downward move without protection against an upward move is by shorting the stock. Shorting stock is like the opposite of buying it. You make the amount of money the stock goes down by, or lose the amount it goes up by. But, since stocks can go up by an infinite amount, your possible loss is unlimited. If you want to profit on a large downward move without an unlimited loss if you're wrong and it goes up, you need something that makes money as the stock drops, but can only lose so much if it goes up. (If you want to be guaranteed to lose nothing, your best investment option is buying US Treasuries, and you're technically still exposed to the risk that US defaults on its debt, although if you're a US resident, you'll likely have bigger problems than your portfolio in that situation.) Buying a put option has the exact asymmetrical exposure you want. You pay a limited premium to buy it, and at expiration you essentially make the full amount that the stock has declined below the strike price, less what you paid for the option. That last part is important - because you pay a premium for the option, if it's down just a little, you might still lose some or all of what you paid for it, which is what you give up in exchange for it limiting your maximum loss. But wait, you might say. When I buy an option, I can lose all of my money, cant I? Yes, you can. Here's the key to understanding the way options limit risk as compared to the corresponding way to get \"\"normal\"\" exposure through getting long, or in your case, short, the stock: If you use the number of options that represent the number of shares you would have bought, you will have much, much less total money at risk. If you spend the same \"\"bag 'o cash\"\" on options as you would have spent on stock, you will have exposure to way more shares, and have the same amount of money at risk as if you bought the stock, but will be much more likely to lose it. The first way limits the total money at risk for a similar level of exposure; the second way gets you exposure to a much larger amount of the stock for the same money, increasing your risk. So the best answer to your described need is already in the question: Buy a put. I'd probably look at GLD to buy it on, simply because it's generally a little more liquid than IAU. And if you're new to options, consider the following: \"\"Paper trade\"\" first. Either just keep track of fake buys and sells on a spreadsheet, or use one of the many online services where you can track investments - they don't know or care if they're real or not. Check out www.888options.com. They are an excellent learning resource that isn't trying to sell you anything - their only reason to exist is to promote options education. If you do put on a trade, don't forget that the most frustrating pitfall with buying options is this: You can be basically right, and still lose some or all of what you invest. This happens two ways, so think about them both before you trade: If the stock goes in the direction you think, but not enough to make back your premium, you can still lose. So you need to make sure you know how far down the stock has to be to make back your premium. At expiration, it's simple: You need it to be below the strike price by more than what you paid for the option. With options, timing is everything. If the stock goes down a ton, or even to zero - free gold! - but only after your option expires, you were essentially right, but lose all your money. So, while you don't want to buy an option that's longer than you need, since the premium is higher, if you're not sure if an expiration is long enough out, it isn't - you need the next one. EDIT to address update: (I'm not sure \"\"not long enough\"\" was the problem here, but...) If the question is just how to ensure there is a limited, defined amount you can lose (even if you want the possible loss to be much less than you can potentially make, the put strategy described already does that - if the stock you use is at $100, and you buy a put with a 100 strike for $5, you can make up to $95. (This occurs if the stock goes to zero, meaning you could buy it for nothing, and sell it for $100, netting $95 after the $5 you paid). But you can only lose $5. So the put strategy covers you. If the goal is to have no real risk of loss, there's no way to have any real gain above what's sometimes called the \"\"risk-free-rate\"\". For simplicity's sake, think of that as what you'd get from US treasuries, as mentioned above. If the goal is to make money whether the stock (or gold) goes either up or down, that's possible, but note that you still have (a fairly high) risk of loss, which occurs if it fails to move either up or down by enough. That strategy, in its most common form, is called a straddle, which basically means you buy a call and a put with the same strike price. Using the same $100 example, you could buy the 100-strike calls for $5, and the 100-strike puts for $5. Now you've spent $10 total, and you make money if the stock is up or down by more than $10 at expiration (over 110, or under 90). But if it's between 90 and 100, you lose money, as one of your options will be worthless, and the other is worth less than the $10 total you paid for them both.\"",
"title": ""
},
{
"docid": "448952",
"text": "I don't think that the trading volume would impact a broker's ability to find shares to short. You might think that a lot more people are trying to short a stock during regular trading hours than in the pre-market, and that's probably true. But what's also true is that a lot more people are covering their shorts during regular trading hours than in the pre-market. For stocks that have difficulty in finding shares to short, any time someone covers a short is an opportunity for you to enter a short. If you want to short a stock and your broker is rejecting your order because they can't find shares to short, then I would recommend that you continue placing that order throughout the day. You might get lucky and submit one of those orders right after someone else has covered their short and before anyone else can enter a short. I have had success doing this in the past.",
"title": ""
},
{
"docid": "151587",
"text": "This is dependent on the broker according to The Options Industry Council. Your broker will specify what they would do upon expiry (or hours before last trade) if you did not indicate your preference. Most likely they will conduct a probabilistic simulation to see whether exercising the contracts may result in margin deficit even after selling the delivered shares under extreme circumstances. In most cases, brokers tend to liquidate the option for you (sell to close) before expiry. I've seen people complain about certain brokers forcing liquidation at terrible bid-ask spreads even though the options are still days to expiry. It is better for you to close the position on your own beforehand. The best brokers would allow margin deficit and let you deposit the required amount of money afterward. Please consult your broker's materials. If you can't find them, use live chat or email tickets.",
"title": ""
},
{
"docid": "376179",
"text": "Coolness - It's not only a matter of staying calm when being up or down. You must keep yourself from chasing a stock that appears to be running away. Or from betting all your money that something(like say a crash) will happen tomorrow because that would be great for you. Use your head not your heart. Empathy - You need to understand what other speculators, investors, institutions and algorithms are going to do when there is a new development or technical signal. And why. For publicly traded corporations, fundamentals and technical indicators only have the value that people(and their algorithms) choose to assign to them at that particular moment. And every stock has a different population trading it. There is no rule of thumb. Patience - To trade successfully, you must avoid trading at all costs. Heh. If you can't find any good trade to do, don't open positions in order to meet your targets, buy a new smartphone, or to fight boredom. Diligence - If your strategy relies on tight stops, don't make exceptions. If your strategy relies on position sizing, don't close when you are a few points down. Luck - In the end almost every trade can turn against you very badly. You must prepare for the worst and hope for the best. You can't buy luck, or get luckier, but you can attempt to stack probabilities: diversify, buy options to insure your positions, reduce holding time, avoid known volatility events, etc.",
"title": ""
},
{
"docid": "585447",
"text": "Before you go filling your head with useless information as there is way too much stuff out there on the stock market. First ask yourself a few questions: There is going to be a balance between the three... don't kid yourself. After you answer these questions find a trading strategy to get the returns you are looking for. Remember the higher returns you expect... the more time you have to put in. Find a trading strategy you like and that works for you. Ounce you have your strategy then find the stocks or ETF that work for that strategy.... Ignore everything else, it is designed to separate you from your money. Making money in the stock market is easy, don't let the media hype and negative people tell you any different. Find something that works for you and perfect it... stick to it.",
"title": ""
},
{
"docid": "116599",
"text": "Well the article did mention that if you continually beat your bookmaker you're likely to get rejected in future which is hilarious, but personally I have actually bet on sports and I've found that it's a fairly easy game to win at if you don't go for bets with huge odds and I don't think I've ever placed a bet where after I lost and said 'what the hell just happened'. I only really bet on rugby and soccer though, so team sports may be a bit less prone to corruption from the bookmakers. I'm not saying I think this is a safe way to do business though, I don't think day trading is either. I think they are both speculation. I just think that sports betting has a lot more for a speculator to work with before they develop a strategy. For instance, I always bet on New Zealand winning a rugby game, their players line up as the top in their respective positions and their game strategy essentially has the rules of the game exploited to the maximum. All of the data on this team based on their past performance is actually applicable to their future performance, skilled players usually continue to be so up till a certain age, skilled coaches who stay in their position mean no variation in team strategy. That makes me feel confident that even though New Zealand might lose a game here or there, that they will continue to be winners, and even though the gains on their wins aren't much, consistently winning with them over time builds up to a nice bit of profit. With day trading in the stock market, so much of the variation in prices is due to non accounting fundamentals, and even though historical data can be useful we know that investor sentiment, secret information, and a myriad of other factors mean that unless you are extremely experienced or have a natural eye for reading markets that most traders will lose. I know developing strategies do work for some people, but I think I've seen it said on this sub a couple times that 'trading strategies work - until they don't.' I only speak as a uni student who has limited research beyond Bloomberg articles etc... but from what I can tell, the majority of day traders lose money eventually, and even with AI, the profits are only noteable when the capital input is extremely high. Sports events can't really be swung by the confidence of supporters, and yes corruption is rampant in sports as with every industry, but at least the data you have tells a fairly good story about where the bets will head in the future.",
"title": ""
},
{
"docid": "234892",
"text": "Yes, exactly. VaR is just a single tailed confidence interval. To go from model to strategy, you need to design some kind of indicator (i.e. when to buy and when to short or stay out). In practice, this will look like a large matrix with values ranging from -1 to 1 (corresponding to shorting and holding respectively) for each security and each day (or hour, or minute, or tick, etc.), which you then just multiply with the matrix of the stock returns. The resulting matrix will be your daily returns for each stock, you can then just row sum for daily returns of a portfolio, or calculate a cumulative product for cumulative returns. A simple example of an indicator would be something like a value of 1 when the price of the stock is below the 30 day moving average, and 0 otherwise. You can use a battery of econometric models to design these indicators, but the rest of the strategy design is essentially the same, and it's *relatively* easy to build a one-size-fits-all back-testing code. I'll try to edit this post later and link a blog that goes through some of the code. Edit: [Here](http://www.signalplot.com/simple-machine-learning-model-trade-spy/) is a post that discusses implementing a simple ML strategy. You can ignore most of the content but if you go through the github, you'll see how the ML model is implemented as a strategy. An even easier example can be found from [the github connected to this post](http://www.signalplot.com/how-to-measure-the-performance-of-a-trading-strategy/), where the author is just using a totally arbitrary signal. As you can see, deriving a signal can be a ton of work, but once you have, actually simulating the strategy can be done in just a few lines of code. Hopefully the author won't mind me linking his page here, but I find his coding style to be very clean and good for educational purposes.",
"title": ""
}
] |
1046
|
Ribosomal protein (RP) expression is controlled in part by stress-activated regulators.
|
[
{
"docid": "4324278",
"text": "The rapamycin-sensitive TOR signalling pathway in Saccharomyces cerevisiae activates a cell-growth program in response to nutrients such as nitrogen and carbon. The TOR1 and TOR2 kinases (TOR) control cytoplasmic protein synthesis and degradation through the conserved TAP42 protein. Upon phosphorylation by TOR, TAP42 binds and possibly inhibits type 2A and type-2A-related phosphatases; however, the mechanism by which TOR controls nuclear events such as global repression of starvation-specific transcription is unknown. Here we show that TOR prevents transcription of genes expressed upon nitrogen limitation by promoting the association of the GATA transcription factor GLN3 with the cytoplasmic protein URE2. The binding of GLN3 to URE2 requires TOR-dependent phosphorylation of GLN3. Phosphorylation and cytoplasmic retention of GLN3 are also dependent on the TOR effector TAP42, and are antagonized by the type-2A-related phosphatase SIT4. TOR inhibits expression of carbon-source-regulated genes by stimulating the binding of the transcriptional activators MSN2 and MSN4 to the cytoplasmic 14-3-3 protein BMH2. Thus, the TOR signalling pathway broadly controls nutrient metabolism by sequestering several transcription factors in the cytoplasm.",
"title": "The TOR signalling pathway controls nuclear localization of nutrient-regulated transcription factors."
},
{
"docid": "16712164",
"text": "Healthy cells utilize intricate systems to monitor their environment and mount robust responses in the event of cellular stress. Whether stress arises from external insults or defects due to mutation and disease, cells must be able to respond precisely to mount the appropriate defenses. Multi-faceted stress responses are generally coupled with arrest of growth and cell-cycle progression, which both limits the transmission of damaged materials and serves to reallocate limited cellular resources toward defense. Therefore, stress defense versus rapid growth represent competing interests in the cell. How eukaryotic cells set the balance between defense versus proliferation, and in particular knowledge of the regulatory networks that control this decision, are poorly understood. In this perspective, we expand upon our recent work inferring the stress-activated signaling network in budding yeast, which captures pathways controlling stress defense and regulators of growth and cell-cycle progression. We highlight similarities between the yeast and mammalian stress responses and explore how stress-activated signaling networks in yeast can inform on signaling defects in human cancers.",
"title": "Exploiting the yeast stress-activated signaling network to inform on stress biology and disease signaling"
},
{
"docid": "418246",
"text": "Stressed cells coordinate a multi-faceted response spanning many levels of physiology. Yet knowledge of the complete stress-activated regulatory network as well as design principles for signal integration remains incomplete. We developed an experimental and computational approach to integrate available protein interaction data with gene fitness contributions, mutant transcriptome profiles, and phospho-proteome changes in cells responding to salt stress, to infer the salt-responsive signaling network in yeast. The inferred subnetwork presented many novel predictions by implicating new regulators, uncovering unrecognized crosstalk between known pathways, and pointing to previously unknown 'hubs' of signal integration. We exploited these predictions to show that Cdc14 phosphatase is a central hub in the network and that modification of RNA polymerase II coordinates induction of stress-defense genes with reduction of growth-related transcripts. We find that the orthologous human network is enriched for cancer-causing genes, underscoring the importance of the subnetwork's predictions in understanding stress biology.",
"title": "Pathway connectivity and signaling coordination in the yeast stress-activated signaling network"
}
] |
[
{
"docid": "12486491",
"text": "Historically, the ribosome has been viewed as a complex ribozyme with constitutive rather than regulatory capacity in mRNA translation. Here we identify mutations of the Ribosomal Protein L38 (Rpl38) gene in mice exhibiting surprising tissue-specific patterning defects, including pronounced homeotic transformations of the axial skeleton. In Rpl38 mutant embryos, global protein synthesis is unchanged; however the translation of a select subset of Homeobox mRNAs is perturbed. Our data reveal that RPL38 facilitates 80S complex formation on these mRNAs as a regulatory component of the ribosome to confer transcript-specific translational control. We further show that Rpl38 expression is markedly enriched in regions of the embryo where loss-of-function phenotypes occur. Unexpectedly, a ribosomal protein (RP) expression screen reveals dynamic regulation of individual RPs within the vertebrate embryo. Collectively, these findings suggest that RP activity may be highly regulated to impart a new layer of specificity in the control of gene expression and mammalian development.",
"title": "Ribosome-Mediated Specificity in Hox mRNA Translation and Vertebrate Tissue Patterning"
},
{
"docid": "12240507",
"text": "Diamond-Blackfan anemia (DBA) is a congenital erythroid hypoplasia caused by haploinsufficiency of genes encoding ribosomal proteins (RPs). Perturbed ribosome biogenesis in DBA has been shown to induce a p53-mediated ribosomal stress response. However, the mechanisms of p53 activation and its relevance for the erythroid defect remain elusive. Previous studies have indicated that activation of p53 is caused by the inhibition of mouse double minute 2 (Mdm2), the main negative regulator of p53, by the 5S ribonucleoprotein particle (RNP). Meanwhile, it is not clear whether this mechanism solely mediates the p53-dependent component found in DBA. To approach this question, we crossed our mouse model for RPS19-deficient DBA with Mdm2C305F knock-in mice that have a disrupted 5S RNP–Mdm2 interaction. Upon induction of the Rps19 deficiency, Mdm2C305F reversed the p53 response and improved expansion of hematopoietic progenitors in vitro, and ameliorated the anemia in vivo. Unexpectedly, disruption of the 5S RNP–Mdm2 interaction also led to selective defect in erythropoiesis. Our findings highlight the sensitivity of erythroid progenitor cells to aberrations in p53 homeostasis mediated by the 5S RNP–Mdm2 interaction. Finally, we provide evidence indicating that physiological activation of the 5S RNP-Mdm2-p53 pathway may contribute to functional decline of the hematopoietic system in a cell-autonomous manner over time.",
"title": "Disruption of the 5S RNP–Mdm2 interaction significantly improves the erythroid defect in a mouse model for Diamond-Blackfan anemia"
},
{
"docid": "22482024",
"text": "Diamond-Blackfan anemia (DBA) is a congenital erythroid aplasia characterized as a normochromic macrocytic anemia with a selective deficiency in red blood cell precursors in otherwise normocellular bone marrow. In 40% of DBA patients, various physical anomalies are also present. Currently two genes are associated with the DBA phenotype--the ribosomal protein (RP) S19 mutated in 25% of DBA patients and RPS24 mutated in approximately 1.4% of DBA patients. Here we report the identification of a mutation in yet another ribosomal protein, RPS17. The mutation affects the translation initiation start codon, changing T to G (c.2T>G), thus eliminating the natural start of RPS17 protein biosynthesis. RNA analysis revealed that the mutated allele was expressed, and the next downstream start codon located at position +158 should give rise to a short peptide of only four amino acids (Met-Ser-Arg-Ile). The mutation arose de novo, since all healthy family members carry the wild-type alleles. The identification of a mutation in the third RP of the small ribosomal subunit in DBA patients further supports the theory that impaired translation may be the main cause of DBA pathogenesis.",
"title": "Ribosomal protein S17 gene (RPS17) is mutated in Diamond-Blackfan anemia."
},
{
"docid": "6670101",
"text": "It is long been known that cancer and non-cancer cells can be distinguished on the basis of their nucleolar morphologies. As early as the 19th century, it was reported that cancer cells have larger and more irregularly shaped nucleoli. Since then, pathologists have used nucleolar morphology to predict the clinical outcome [1]. Nucleolar morphology is altered due to the up-regulation of ribosomal gene transcription. Within nucleoli, ribosomal genes (rDNA) are transcribed by RNA polymerase I (pol I). The pre-ribosomal RNA (pre-rRNA) transcripts are subsequently modified and processed into the mature 18S, 5.8S and 28S rRNAs. 5S rRNA is transcribed by RNA polymerase III in the nucleoplasm. Together with the ribosomal proteins, the 5S rRNA is imported into the nucleolus where 40S and 60S ribosomal subunits are assembled prior to export to the cytoplasm [1, 2]. Oncogenes such as c-Myc can both directly and indirectly upregulate rDNA transcription, while tumour suppressors like p53 and Rb suppress ribosome biogenesis. Mutations in these genes not only result in deregulated cell cycle control, but also upregulated ribosome biogenesis. In addition to ribosome biogenesis, the nucleolus is a key cellular stress sensor and plays a central role in p53 activation [1, 2]. The increased translational capacity of cancer cells enables them to maintain higher proliferation rates. As stated by Ruggero, “compared with normal cells, cancer cells may be addicted to increases in ribosome biogenesis and number” [1]. This provides new therapeutic opportunities. As it turns out many chemotherapeutic drugs used in cancer treatment already inhibit ribosome biogenesis. In one recent survey it was shown that 20 out of 36 drugs in clinical use inhibit ribosome biogenesis [3]. Most of these drugs were originally designed to target highly proliferating cells by damaging DNA, interfering with DNA synthesis or with mitosis. These targeting modalities of these drugs also lead to toxicity in normal highly proliferating tissues. An example is ActinomycinD (AMD), a DNA intercalator which has a preference for GC-rich DNA sequences. As rDNA has above average GC-richness and because of its open chromatin conformation, low concentrations of AMD preferentially inhibit RNA polymerase I transcription and upon prolonged exposure causes genome wide DNA damage. Alkylating drugs like cisplatin and oxaliplatin or topoisomerases poisons like camptothecin inhibit pol I transcription. The degree to which inhibition of ribosome biogenesis contributes to the efficacy of these drugs is difficult to establish [3]. This raises an important question. Can targeting ribosome biogenesis without DNA damage offer any therapeutic potential? Two recently described drugs CX-5461 and BMH-21 are now providing evidence that inhibition of ribosome biogenesis by targeting transcription of rDNA by pol I has promising therapeutic potential. CX-5461 was designed to specifically inhibit pol I transcription by disrupting pre-initiation complex formation at the rDNA promoter. CX-5461 has been shown to activate p53 via nucleolar stress. It induces autophagy as well as senescence in a multiple types of cancer cells in a p53-dependent manner. Especially in leukaemia and lymphoma cells, treatment with CX-5461 induces p53-dependent apoptosis, while normal cells tolerate it [4, 5]. Whether the drug also induces DNA damage was not fully addressed, but it was demonstrated that it could induce cell death in cells lacking ATM - a key mediator of DNA double strand break responses. However, more recently Laiho and colleagues have shown that at high concentrations, CX-5461 does induce a γH2AX response, raising concerns about DNA damage [6]. BMH-21 was identified in a screen performed by Laiho and colleagues aimed at identifying novel p53 activators. Like AMD, BMH-21 is a DNA intercalator with preference for GC rich sequences [7]. Continuing the parallel with AMD, BMH-21 is a potent and specific inhibitor rDNA transcription and induces nucleolar reorganisation often referred to as nucleolar capping. Interestingly, transcription inhibition was followed by the degradation of the main pol I subunit, RPA194, by the proteasome [6]. In contrast with AMD, initial indications were that BMH-21 did not appear to induce DNA damage as evidenced by the lack of a γH2AX response [7]. Inhibition of transcription by BMH-21 causes nucleolar stress, resulting in decreased proliferation and cell death. P53 is activated in BMH-21 treated cells but is not required for its anti-proliferative effects. Intriguingly, it appears that cancer cells with high demands for ribosome biogenesis are selectively targeted [6]. The current publication in Oncotarget now rules out any role for DNA damage signalling and repair pathways in the BMH-21 response. Moreover, BMH-21 derivatives that can induce DNA damage display lower efficiency in inducing nucleolar stress and inhibiting proliferation [8]. The central importance of this study is that it finally uncouples DNA damage and nucleolar stress and reveals an Achilles heel in cancer cells, their addiction to ribosome biogenesis.",
"title": "Ribosome biogenesis: Achilles heel of cancer?"
},
{
"docid": "18987782",
"text": "The Myc oncogene regulates the expression of several components of the protein synthetic machinery, including ribosomal proteins, initiation factors of translation, RNA polymerase III and ribosomal DNA. Whether and how increasing the cellular protein synthesis capacity affects the multistep process leading to cancer remains to be addressed. Here we use ribosomal protein heterozygote mice as a genetic tool to restore increased protein synthesis in Emu-Myc/+ transgenic mice to normal levels, and show that the oncogenic potential of Myc in this context is suppressed. Our findings demonstrate that the ability of Myc to increase protein synthesis directly augments cell size and is sufficient to accelerate cell cycle progression independently of known cell cycle targets transcriptionally regulated by Myc. In addition, when protein synthesis is restored to normal levels, Myc-overexpressing precancerous cells are more efficiently eliminated by programmed cell death. Our findings reveal a new mechanism that links increases in general protein synthesis rates downstream of an oncogenic signal to a specific molecular impairment in the modality of translation initiation used to regulate the expression of selective messenger RNAs. We show that an aberrant increase in cap-dependent translation downstream of Myc hyperactivation specifically impairs the translational switch to internal ribosomal entry site (IRES)-dependent translation that is required for accurate mitotic progression. Failure of this translational switch results in reduced mitotic-specific expression of the endogenous IRES-dependent form of Cdk11 (also known as Cdc2l and PITSLRE), which leads to cytokinesis defects and is associated with increased centrosome numbers and genome instability in Emu-Myc/+ mice. When accurate translational control is re-established in Emu-Myc/+ mice, genome instability is suppressed. Our findings demonstrate how perturbations in translational control provide a highly specific outcome for gene expression, genome stability and cancer initiation that have important implications for understanding the molecular mechanism of cancer formation at the post-genomic level.",
"title": "Suppression of Myc oncogenic activity by ribosomal protein haploinsufficiency"
},
{
"docid": "26596106",
"text": "In the yeast S. cerevisiae, ribosome assembly is linked to environmental conditions by the coordinate transcriptional regulation of genes required for ribosome biogenesis. In this study we show that two nonessential stress-responsive genes, YAR1 and LTV1, function in 40S subunit production. We provide genetic and biochemical evidence that Yar1, a small ankyrin-repeat protein, physically interacts with RpS3, a component of the 40S subunit, and with Ltv1, a protein recently identified as a substoichiometric component of a 43S preribosomal particle. We demonstrate that cells lacking YAR1 or LTV1 are hypersensitive to particular protein synthesis inhibitors and exhibit aberrant polysome profiles, with a reduced absolute number of 40S subunits and an excess of free 60S subunits. Surprisingly, both mutants are also hypersensitive to a variety of environmental stress conditions. Overexpression of RPS3 suppresses both the stress sensitivity and the ribosome biogenesis defect of Deltayar1 mutants, but does not suppress either defect in Deltaltv1 mutants. We propose that YAR1 and LTV1 play distinct, nonessential roles in 40S subunit production. The stress-sensitive phenotypes of strains lacking these genes reveal a hitherto unknown link between ribosome biogenesis factors and environmental stress sensitivity.",
"title": "Genetic and biochemical interactions among Yar1, Ltv1 and Rps3 define novel links between environmental stress and ribosome biogenesis in Saccharomyces cerevisiae."
},
{
"docid": "24737389",
"text": "Ribosome biogenesis and protein synthesis are two of the most energy consuming processes in a growing cell. Moreover, defects in their molecular components can alter the pattern of gene expression. Thus it is understandable that cells have developed a surveillance system to monitor the status of the translational machinery. Recent discoveries of causative mutations and deletions in genes linked to ribosome biogenesis have defined a group of similar pathologies termed ribosomopathies. Over the past decade, much has been learned regarding the relationship between growth control and ribosome biogenesis. The discovery of extra-ribosomal functions of several ribosome proteins and their regulation of p53 levels has provided a link from ribosome impairment to cell cycle regulation. Yet, evidence suggesting p53 and/or Hdm2 independent pathways also exists. In this review, we summarize recent advances in understanding the mechanisms underlying the pathologies of ribosomopathies and discuss the relationship between ribosome production and tumorigenesis.",
"title": "Growth control and ribosomopathies."
},
{
"docid": "2851611",
"text": "Expression of particular drug transporters in response to antibiotic pressure is a critical element in the development of bacterial multidrug resistance, and represents a serious concern for human health. To obtain a better understanding of underlying regulatory mechanisms, we have dissected the transcriptional activation of the ATP-binding cassette (ABC) transporter BmrC/BmrD of the Gram-positive model bacterium Bacillus subtilis. By using promoter-GFP fusions and live cell array technology, we demonstrate a temporally controlled transcriptional activation of the bmrCD genes in response to antibiotics that target protein synthesis. Intriguingly, bmrCD expression only occurs during the late-exponential and stationary growth stages, irrespective of the timing of the antibiotic challenge. We show that this is due to tight transcriptional control by the transition state regulator AbrB. Moreover, our results show that the bmrCD genes are co-transcribed with bmrB (yheJ), a small open reading frame immediately upstream of bmrC that harbors three alternative stem-loop structures. These stem-loops are apparently crucial for antibiotic-induced bmrCD transcription. Importantly, the antibiotic-induced bmrCD expression requires translation of bmrB, which implies that BmrB serves as a regulatory leader peptide. Altogether, we demonstrate for the first time that a ribosome-mediated transcriptional attenuation mechanism can control the expression of a multidrug ABC transporter.",
"title": "The multidrug ABC transporter BmrC/BmrD of Bacillus subtilis is regulated via a ribosome-mediated transcriptional attenuation mechanism"
},
{
"docid": "36904081",
"text": "The yeast ribosomal protein gene RPL32 of Saccharomyces cerevisiae is of particular interest for two reasons: 1) it is adjacent to another ribosomal protein gene, RP29, whose divergent transcription may be driven from the same control sequences, and 2) it appears that the splicing of its transcript is regulated by the product of the gene, ribosomal protein in L32. RPL32 has been analyzed in detail. It is essential for cell growth. Its sequence predicts L32 to be a protein of 105 amino acids, somewhat basic near the NH2 terminus, rather acidic near the COOH terminus, and homologous to ribosomal protein L30 of mammals. The reading frame has been confirmed by partial NH2-terminal analysis of L32. The nucleotide sequence also predicts an intron of 230 nucleotides, which begins with the unusual sequence GTCAGT and ends 40 nucleotides downstream of the consensus sequence TAC-TAAC. The intron has been confirmed by determination of the sequence of a cDNA clone. Transcription initiates 58 nucleotides upstream of the AUG initiation codon, and the polyadenylation site occurs 100 nucleotides downstream of the termination codon. Regulation of the transcription of ribosomal protein genes has been linked to two related consensus sequences. Analysis of the intergenic region between RP29 and RPL32 reveals three copies of these sequences. A deletion removing all three sequences reduces synthesis of a L32-LacZ fusion protein by more than 90%. Some residual activity, however, remains.",
"title": "The yeast ribosomal protein L32 and its gene."
},
{
"docid": "25488034",
"text": "Increases in the intracellular levels of reactive oxygen species (ROS), frequently referred to as oxidative stress, represents a potentially toxic insult which if not counteracted will lead to membrane dysfunction, DNA damage and inactivation of proteins. Chronic oxidative stress has numerous pathological consequences including cancer, arthritis and neurodegenerative disease. Glutathione-associated metabolism is a major mechanism for cellular protection against agents which generate oxidative stress. It is becoming increasingly apparent that the glutathione tripeptide is central to a complex multifaceted detoxification system, where there is substantial inter-dependence between separate component members. Glutathione participates in detoxification at several different levels, and may scavenge free radicals, reduce peroxides or be conjugated with electrophilic compounds. Thus, glutathione provides the cell with multiple defences not only against ROS but also against their toxic products. This article discusses how glutathione biosynthesis, glutathione peroxidases, glutathione S-transferases and glutathione S-conjugate efflux pumps function in an integrated fashion to allow cellular adaption to oxidative stress. Co-ordination of this response is achieved, at least in part, through the antioxidant responsive element (ARE) which is found in the promoters of many of the genes that are inducible by oxidative and chemical stress. Transcriptional activation through this enhancer appears to be mediated by basic leucine zipper transcription factors such as Nrf and small Maf proteins. The nature of the intracellular sensor(s) for ROS and thiol-active chemicals which induce genes through the ARE is described. Gene activation through the ARE appears to account for the enhanced antioxidant and detoxification capacity of normal cells effected by many cancer chemopreventive agents. In certain instances it may also account for acquired resistance of tumours to cancer chemotherapeutic drugs. It is therefore clear that determining the mechanisms involved in regulation of ARE-driven gene expression has enormous medical implications.",
"title": "Glutathione and glutathione-dependent enzymes represent a co-ordinately regulated defence against oxidative stress."
},
{
"docid": "10029970",
"text": "CDD, the Conserved Domain Database, is part of NCBI's Entrez query and retrieval system and is also accessible via http://www.ncbi.nlm.nih.gov/Structure/cdd/cdd.shtml. CDD provides annotation of protein sequences with the location of conserved domain footprints and functional sites inferred from these footprints. Pre-computed annotation is available via Entrez, and interactive search services accept single protein or nucleotide queries, as well as batch submissions of protein query sequences, utilizing RPS-BLAST to rapidly identify putative matches. CDD incorporates several protein domain and full-length protein model collections, and maintains an active curation effort that aims at providing fine grained classifications for major and well-characterized protein domain families, as supported by available protein three-dimensional (3D) structure and the published literature. To this date, the majority of protein 3D structures are represented by models tracked by CDD, and CDD curators are characterizing novel families that emerge from protein structure determination efforts.",
"title": "CDD: conserved domains and protein three-dimensional structure"
},
{
"docid": "7506409",
"text": "Human mesenchymal stem cells (hMSCs) have been widely studied as a source of primary adult stem cells for cell therapy because of their multidifferentiation potential; however, the growth arrest (also known as \"premature senescence\") often found in hMSCs cultured in vitro has been a major obstacle to the in-depth characterization of these cells. In addition, the inability to maintain constant cell growth hampers the development of additional genetic modifications aimed at achieving desired levels of differentiation to specific tissues; however, the molecular mechanisms that govern this phenomenon remain unclear, with the exception of a few studies demonstrating that induction of p16INK4a is responsible for this senescence-like event. Here, we observed that the premature growth arrest in hMSCs occurs in parallel with the induction of p16INK4a, following abrogation of inhibitory phosphorylation of retinoblastoma protein. These stress responses were concurrent with increased formation of reactive oxygen species (ROSs) from mitochondria and increased p38 mitogen-activated protein kinase (MAPK) activity. The introduction of Wip1 (wild-type p53 inducible phosphatase-1), a well-studied stress modulator, significantly lowered p16INK4a expression and led to p38 MAPK inactivation, although it failed to affect the levels of ROSs. Moreover, the suppression of stress responses by Wip1 apparently extended the life span of hMSCs, compared with control conditions, while maintaining their multilineage differentiation potential. Based on these results, we suggest that senescent growth arrest in hMSCs may result from activation of stress signaling pathways and consequent onset of stress responses, due in part to ROS production during prolonged in vitro culture.",
"title": "Senescent growth arrest in mesenchymal stem cells is bypassed by Wip1-mediated downregulation of intrinsic stress signaling pathways."
},
{
"docid": "2582169",
"text": "The importance of coordinating cell growth with proliferation has been recognized for a long time. The molecular basis of this relationship, however, is poorly understood. Here we show that the ribosomal protein L23 interacts with HDM2. The interaction involves the central acidic domain of HDM2 and an N-terminal domain of L23. L23 and L11, another HDM2-interacting ribosomal protein, can simultaneously yet distinctly interact with HDM2 together to form a ternary complex. We show that, when overexpressed, L23 inhibits HDM2-induced p53 polyubiquitination and degradation and causes a p53-dependent cell cycle arrest. On the other hand, knocking down L23 causes nucleolar stress and triggers translocation of B23 from the nucleolus to the nucleoplasm, leading to stabilization and activation of p53. Our data suggest that cells may maintain a steady-state level of L23 during normal growth; alternating the levels of L23 in response to changing growth conditions could impinge on the HDM2-p53 pathway by interrupting the integrity of the nucleolus.",
"title": "Inhibition of HDM2 and activation of p53 by ribosomal protein L23."
},
{
"docid": "16527698",
"text": "To shed further light on the primary alterations of insulin secretion in type 2 diabetes and the possible mechanisms involved, we studied several functional and molecular properties of islets isolated from the pancreata of 13 type 2 diabetic and 13 matched nondiabetic cadaveric organ donors. Glucose-stimulated insulin secretion from type 2 diabetic islets was significantly lower than from control islets, whereas arginine- and glibenclamide-stimulated insulin release was less markedly affected. The defects were accompanied by reduced mRNA expression of GLUT1 and -2 and glucokinase and by diminished glucose oxidation. In addition, AMP-activated protein kinase activation was reduced. Furthermore, the expression of insulin was decreased, and that of pancreatic duodenal homeobox-1 (PDX-1) and forkhead box O1 (Foxo-1) was increased. Nitrotyrosine and 8-hydroxy-2'-deoxyguanosine concentrations, markers of oxidative stress, were significantly higher in type 2 diabetic than control islets, and they were correlated with the degree of glucose-stimulated insulin release impairment. Accordingly, 24-h exposure to glutathione significantly improved glucose-stimulated insulin release and decreased nitrotyrosine concentration, with partial recovery of insulin mRNA expression. These results provide direct evidence that the defects of insulin secretion in type 2 diabetic islets are associated with multiple islet cell alterations. Most importantly, the current study shows that the functional impairment of type 2 diabetic islets can be, at least in part, reversible. In this regard, it is suggested that reducing islet cell oxidative stress is a potential target of human type 2 diabetes therapy.",
"title": "Functional and molecular defects of pancreatic islets in human type 2 diabetes."
},
{
"docid": "7487927",
"text": "The production of ribosomes is ubiquitous and fundamental to life. As such, it is surprising that defects in ribosome biogenesis underlie a growing number of symptomatically distinct inherited disorders, collectively called ribosomopathies. We previously determined that the nucleolar protein, NOL11, is essential for optimal pre-rRNA transcription and processing in human tissue culture cells. However, the role of NOL11 in the development of a multicellular organism remains unknown. Here, we reveal a critical function for NOL11 in vertebrate ribosome biogenesis and craniofacial development. Nol11 is strongly expressed in the developing cranial neural crest (CNC) of both amphibians and mammals, and knockdown of Xenopus nol11 results in impaired pre-rRNA transcription and processing, increased apoptosis, and abnormal development of the craniofacial cartilages. Inhibition of p53 rescues this skeletal phenotype, but not the underlying ribosome biogenesis defect, demonstrating an evolutionarily conserved control mechanism through which ribosome-impaired craniofacial cells are removed. Excessive activation of this mechanism impairs craniofacial development. Together, our findings reveal a novel requirement for Nol11 in craniofacial development, present the first frog model of a ribosomopathy, and provide further insight into the clinically important relationship between specific ribosome biogenesis proteins and craniofacial cell survival.",
"title": "The Ribosome Biogenesis Factor Nol11 Is Required for Optimal rDNA Transcription and Craniofacial Development in Xenopus "
},
{
"docid": "22908536",
"text": "Nonreplicating and metabolically quiescent bacteria are implicated in latent tuberculosis infections and relapses following \"sterilizing\" chemotherapy. However, evidence linking bacterial dormancy and persistence in vivo is largely inconclusive. Here we measure the single-cell dynamics of Mycobacterium tuberculosis replication and ribosomal activity using quantitative time-lapse microscopy and a reporter of ribosomal RNA gene expression. Single-cell dynamics exhibit heterogeneity under standard growth conditions, which is amplified by stressful conditions such as nutrient limitation, stationary phase, intracellular replication, and growth in mouse lungs. Additionally, the lungs of chronically infected mice harbor a subpopulation of nongrowing but metabolically active bacteria, which are absent in mice lacking interferon-γ, a cytokine essential for antituberculosis immunity. These cryptic bacterial forms are prominent in mice treated with the antituberculosis drug isoniazid, suggesting a role in postchemotherapeutic relapses. Thus, amplification of bacterial phenotypic heterogeneity in response to host immunity and drug pressure may contribute to tuberculosis persistence.",
"title": "Stress and host immunity amplify Mycobacterium tuberculosis phenotypic heterogeneity and induce nongrowing metabolically active forms."
},
{
"docid": "12909503",
"text": "DNA damage encountered by DNA replication forks poses risks of genome destabilization, a precursor to carcinogenesis. Damage checkpoint systems cause cell cycle arrest, promote repair and induce programed cell death when damage is severe. Checkpoints are critical parts of the DNA damage response network that act to suppress cancer. DNA damage and perturbation of replication machinery causes replication stress, characterized by accumulation of single-stranded DNA bound by replication protein A (RPA), which triggers activation of ataxia telangiectasia and Rad3 related (ATR) and phosphorylation of the RPA32, subunit of RPA, leading to Chk1 activation and arrest. DNA-dependent protein kinase catalytic subunit (DNA-PKcs) [a kinase related to ataxia telangiectasia mutated (ATM) and ATR] has well characterized roles in DNA double-strand break repair, but poorly understood roles in replication stress-induced RPA phosphorylation. We show that DNA-PKcs mutant cells fail to arrest replication following stress, and mutations in RPA32 phosphorylation sites targeted by DNA-PKcs increase the proportion of cells in mitosis, impair ATR signaling to Chk1 and confer a G2/M arrest defect. Inhibition of ATR and DNA-PK (but not ATM), mimic the defects observed in cells expressing mutant RPA32. Cells expressing mutant RPA32 or DNA-PKcs show sustained H2AX phosphorylation in response to replication stress that persists in cells entering mitosis, indicating inappropriate mitotic entry with unrepaired damage.",
"title": "Distinct roles for DNA-PK, ATM and ATR in RPA phosphorylation and checkpoint activation in response to replication stress"
},
{
"docid": "24185667",
"text": "The stress-activated kinase JNK mediates key cellular responses to oxidative stress. Here we show that DAP kinase (DAPk), a cell death promoting Ser/Thr protein kinase, plays a main role in oxidative stress-induced JNK signaling. We identify protein kinase D (PKD) as a novel substrate of DAPk and demonstrate that DAPk physically interacts with PKD in response to oxidative stress. We further show that DAPk activates PKD in cells and that induction of JNK phosphorylation by ectopically expressed DAPk can be attenuated by knocking down PKD expression or by inhibiting its catalytic activity. Moreover, knockdown of DAPk expression caused a marked reduction in JNK activation under oxidative stress, indicating that DAPk is indispensable for the activation of JNK signaling under these conditions. Finally, DAPk is shown to be required for cell death under oxidative stress in a process that displays the characteristics of caspase-independent necrotic cell death. Taken together, these findings establish a major role for DAPk and its specific interaction with PKD in regulating the JNK signaling network under oxidative stress.",
"title": "DAP kinase regulates JNK signaling by binding and activating protein kinase D under oxidative stress"
},
{
"docid": "17055665",
"text": "FoxO transcription factors, inhibited by insulin/insulin-like growth factor signalling (IIS), are crucial players in numerous organismal processes including lifespan. Using genomic tools, we uncover over 700 direct dFOXO targets in adult female Drosophila. dFOXO is directly required for transcription of several IIS components and interacting pathways, such as TOR, in the wild-type fly. The genomic locations occupied by dFOXO in adults are different from those observed in larvae or cultured cells. These locations remain unchanged upon activation by stresses or reduced IIS, but the binding is increased and additional targets activated upon genetic reduction in IIS. We identify the part of the IIS transcriptional response directly controlled by dFOXO and the indirect effects and show that parts of the transcriptional response to IIS reduction do not require dfoxo. Promoter analyses revealed GATA and other forkhead factors as candidate mediators of the indirect and dfoxo-independent effects. We demonstrate genome-wide evolutionary conservation of dFOXO targets between the fly and the worm Caenorhabditis elegans, enriched for a second tier of regulators including the dHR96/daf-12 nuclear hormone receptor.",
"title": "Genome-wide dFOXO targets and topology of the transcriptomic response to stress and insulin signalling"
},
{
"docid": "22896970",
"text": "Protein synthesis in all organisms is catalyzed by ribosomes. In comparison to their prokaryotic counterparts, eukaryotic ribosomes are considerably larger and are subject to more complex regulation. The large ribosomal subunit (60S) catalyzes peptide bond formation and contains the nascent polypeptide exit tunnel. We present the structure of the 60S ribosomal subunit from Tetrahymena thermophila in complex with eukaryotic initiation factor 6 (eIF6), cocrystallized with the antibiotic cycloheximide (a eukaryotic-specific inhibitor of protein synthesis), at a resolution of 3.5 angstroms. The structure illustrates the complex functional architecture of the eukaryotic 60S subunit, which comprises an intricate network of interactions between eukaryotic-specific ribosomal protein features and RNA expansion segments. It reveals the roles of eukaryotic ribosomal protein elements in the stabilization of the active site and the extent of eukaryotic-specific differences in other functional regions of the subunit. Furthermore, it elucidates the molecular basis of the interaction with eIF6 and provides a structural framework for further studies of ribosome-associated diseases and the role of the 60S subunit in the initiation of protein synthesis.",
"title": "Crystal structure of the eukaryotic 60S ribosomal subunit in complex with initiation factor 6."
},
{
"docid": "471735",
"text": "Escherichia coli responds to the redox stress imposed by superoxide-generating agents such as paraquat by activating the synthesis of as many as 80 polypeptides. Expression of a key group of these inducible proteins is controlled at the transcriptional level by the soxRS locus (the soxRS regulon). A two-stage control system was hypothesized for soxRS, in which an intracellular redox signal would trigger the SoxR protein as a transcriptional activator of the soxS gene and the resulting increased levels of SoxS protein would activate transcription of the various soxRS regulon genes (B. Demple and C.F. Amábile Cuevas, Cell 67:837-839, 1990). We have constructed operon fusions of the E. coli lac genes to the soxS promoter to monitor soxS transcription. Expression from the soxS promoter is strongly inducible by paraquat in a manner strictly dependent on a functional soxR gene. Several other superoxide-generating agents also trigger soxR(+)-dependent soxS expression, and the inductions by paraquat and phenazine methosulfate were dependent on the presence of oxygen. Numerous other oxidative stress agents (H2O2, gamma rays, heat shock, etc.) failed to induce soxS, while aerobic growth of superoxide dismutase-deficient bacteria triggered soxR-dependent soxS expression. These results indicate a specific redox signal for soxS induction. A direct role for SoxR protein in the activation of the soxS gene is indicated by band-shift and DNase I footprinting experiments that demonstrate specific binding of the SoxR protein in cell extracts to the soxS promoter. The mode of SoxR binding to DNA appears to be similar to that of its homolog MerR in that the SoxR footprint spans the -10 to -35 region of the soxS promoter.",
"title": "Two-stage control of an oxidative stress regulon: the Escherichia coli SoxR protein triggers redox-inducible expression of the soxS regulatory gene."
},
{
"docid": "12086599",
"text": "Major eukaryotic genomic elements, including the ribosomal DNA (rDNA), are composed of repeated sequences with well-defined copy numbers that must be maintained by regulated recombination. Although mechanisms that instigate rDNA recombination have been identified, none are directional and they therefore cannot explain precise repeat number control. Here, we show that yeast lacking histone chaperone Asf1 undergo reproducible rDNA repeat expansions. These expansions do not require the replication fork blocking protein Fob1 and are therefore independent of known rDNA expansion mechanisms. We propose the existence of a regulated rDNA repeat gain pathway that becomes constitutively active in asf1Δ mutants. Cells lacking ASF1 accumulate rDNA repeats with high fidelity in a processive manner across multiple cell divisions. The mechanism of repeat gain is dependent on highly repetitive sequence but, surprisingly, is independent of the homologous recombination proteins Rad52, Rad51 and Rad59. The expansion mechanism is compromised by mutations that decrease the processivity of DNA replication, which leads to progressive loss of rDNA repeats. Our data suggest that a novel mode of break-induced replication occurs in repetitive DNA that is dependent on high homology but does not require the canonical homologous recombination machinery.",
"title": "Repeat expansion in the budding yeast ribosomal DNA can occur independently of the canonical homologous recombination machinery"
},
{
"docid": "43602749",
"text": "Chromosome breakage elicits transient silencing of ribosomal RNA synthesis, but the mechanisms involved remained elusive. Here we discover an in trans signalling mechanism that triggers pan-nuclear silencing of rRNA transcription in response to DNA damage. This is associated with transient recruitment of the Nijmegen breakage syndrome protein 1 (NBS1), a central regulator of DNA damage responses, into the nucleoli. We further identify TCOF1 (also known as Treacle), a nucleolar factor implicated in ribosome biogenesis and mutated in Treacher Collins syndrome, as an interaction partner of NBS1, and demonstrate that NBS1 translocation and accumulation in the nucleoli is Treacle dependent. Finally, we provide evidence that Treacle-mediated NBS1 recruitment into the nucleoli regulates rRNA silencing in trans in the presence of distant chromosome breaks.",
"title": "The NBS1–Treacle complex controls ribosomal RNA transcription in response to DNA damage"
},
{
"docid": "6259170",
"text": "Nuclear factor erythroid-derived 2-related factor 2 (Nrf2) was originally identified as a positive regulator of drug detoxifying enzyme gene expression during exposure to environmental electrophiles. Currently, Nrf2 is known to regulate the expression of hundreds of cytoprotective genes to counteract endogenously or exogenously generated oxidative stress. Furthermore, when activated in human tumors by somatic mutations, Nrf2 confers growth advantages and chemoresistance by regulating genes involved in various processes such as the pentose phosphate pathway and nucleotide synthesis in addition to antioxidant proteins. Interestingly, increasing evidence shows that Nrf2 is associated with mitochondrial biogenesis during environmental stresses in certain tissues such as the heart. Furthermore, SKN-1, a functional homolog of Nrf2 in C. elegans, is activated by mitochondrial reactive oxygen species and extends life span by promoting mitochondrial homeostasis (i.e., mitohormesis). Similarly, Nrf2 activation was recently observed in the heart of surfeit locus protein 1 (Surf1) -/- mice in which cellular respiration was decreased due to cytochrome c oxidase defects. In this review, we critically examine the relationship between Nrf2 and mitochondria and argue that the Nrf2 stress pathway intimately communicates with mitochondria to maintain cellular homeostasis during oxidative stress.",
"title": "Emerging functional cross-talk between the Keap1-Nrf2 system and mitochondria"
},
{
"docid": "935538",
"text": "RNA-binding proteins are at the heart of posttranscriptional gene regulation, coordinating the processing, storage, and handling of cellular RNAs. We show here that GRSF1, previously implicated in the binding and selective translation of influenza mRNAs, is targeted to mitochondria where it forms granules that colocalize with foci of newly synthesized mtRNA next to mitochondrial nucleoids. GRSF1 preferentially binds RNAs transcribed from three contiguous genes on the light strand of mtDNA, the ND6 mRNA, and the long noncoding RNAs for cytb and ND5, each of which contains multiple consensus binding sequences. RNAi-mediated knockdown of GRSF1 leads to alterations in mitochondrial RNA stability, abnormal loading of mRNAs and lncRNAs on the mitochondrial ribosome, and impaired ribosome assembly. This results in a specific protein synthesis defect and a failure to assemble normal amounts of the oxidative phosphorylation complexes. These data implicate GRSF1 as a key regulator of posttranscriptional mitochondrial gene expression.",
"title": "The mitochondrial RNA-binding protein GRSF1 localizes to RNA granules and is required for posttranscriptional mitochondrial gene expression."
},
{
"docid": "3943235",
"text": "During physiological or psychological stress, catecholamines produced by the sympathetic nervous system (SNS) regulate the immune system. Previous studies report that the activation of β-adrenergic receptors (βARs) mediates the actions of catecholamines and increases pro-inflammatory cytokine production in a number of different cell types. The impact of the SNS on the immune modulation of social defeat has not been examined. The following studies were designed to determine whether SNS activation during social disruption stress (SDR) influences anxiety-like behavior as well as the activation, priming, and glucocorticoid resistance of splenocytes after social stress. CD-1 mice were exposed to one, three, or six cycles of SDR and HPLC analysis of the plasma and spleen revealed an increase in catecholamines. After six cycles of SDR the open field test was used to measure behaviors characteristic of anxiety and indicated that the social defeat induced increase in anxiety-like behavior was blocked by pre-treatment with the β-adrenergic antagonist propranolol. Pre-treatment with the β-adrenergic antagonist propranolol did not significantly alter corticosterone levels indicating no difference in activation of the hypothalamic-pituitary-adrenal axis. In addition to anxiety-like behavior the SDR induced splenomegaly and increase in plasma IL-6, TNFα, and MCP-1 were each reversed by pre-treatment with propranolol. Furthermore, flow cytometric analysis of cells from propranolol pretreated mice reduced the SDR-induced increase in the percentage of CD11b(+) splenic macrophages and significantly decreased the expression of TLR2, TLR4, and CD86 on the surface of these cells. In addition, supernatants from 18h LPS-stimulated ex vivo cultures of splenocytes from propranolol-treated SDR mice contained less IL-6. Likewise propranolol pre-treatment abrogated the glucocorticoid insensitivity of CD11b(+) cells ex vivo when compared to splenocytes from SDR vehicle-treated mice. Together, this study demonstrates that the immune activation and priming effects of SDR result, in part, as a consequence of SNS activation.",
"title": "Beta adrenergic blockade decreases the immunomodulatory effects of social disruption stress"
},
{
"docid": "34386619",
"text": "The Bacillus subtilis clpC operon is regulated by two stress induction pathways relying on either sigmaB or a class III stress induction mechanism acting at a sigmaA-like promoter. When the clpC operon was placed under the control of the isopropyl-beta-D-thiogalactopyranoside (IPTG)-inducible Pspac promoter, dramatic repression of the natural clpC promoters fused to a lacZ reporter gene was noticed after IPTG induction. This result strongly indicated negative regulation of the clpC operon by one of its gene products. Indeed, the negative regulator could be identified which is encoded by the first gene of the clpC operon, ctsR, containing a predicted helix-turn-helix DNA-binding motif. Deletion of ctsR abolished the negative regulation and resulted in high expression of both the clpC operon and the clpP gene under nonstressed conditions. Nevertheless, a further increase in clpC and clpP mRNA levels was observed after heat shock, even in the absence of sigmaB, suggesting a second induction mechanism at the vegetative promoter. Two-dimensional gel analysis and mRNA studies showed that the expression of other class III stress genes was at least partially influenced by the ctsR deletion. Studies with different clpC promoter fragments either fused to the reporter gene bgaB or used in gel mobility shift experiments with the purified CtsR protein revealed a possible target region where the repressor seemed to bind in vivo and in vitro. Our data demonstrate that the CtsR protein acts as a global repressor of the clpC operon, as well as other class III heat shock genes, by preventing unstressed transcription from either the sigmaB- or sigmaA-dependent promoter and might be inactivated or dissociate under inducing stress conditions.",
"title": "The first gene of the Bacillus subtilis clpC operon, ctsR, encodes a negative regulator of its own operon and other class III heat shock genes."
},
{
"docid": "26071782",
"text": "Latent membrane protein 1 (LMP1), an oncoprotein encoded by Epstein–Barr virus (EBV), is an integral membrane protein, which acts like a constitutively active receptor. LMP1 is critical for some facet of EBV's induction and maintenance of proliferation of infected B cells. It, in part, mimics signaling by the CD40 receptor and has been implicated in regulating proliferation, survival, or both properties of EBV-infected cells. We established a conditional LMP1 allele in the context of the intact EBV genome to define the immediate-early cellular target genes regulated by LMP1 in order to assess its contributions to infected human B cells. The functional analysis of this conditional system indicated that LMP1 specifically induces mitogenic B-cell activation through c-myc and Jun/AP1 family members and confirms its direct role in upregulating expression of multiple genes with opposing activities involved in cell survival. LMP1's signals were found to be essential for the G1/S transition in human B cells; cells lacking LMP1's signals are cell cycle arrested and survive quiescently. LMP1's activities are therefore not required to maintain survival in nonproliferating cells. LMP1 does induce both pro- and antiapoptotic genes whose balance seems to permit survival during LMP1's induction and maintenance of proliferation.",
"title": "Latent membrane protein 1 of Epstein–Barr virus coordinately regulates proliferation with control of apoptosis"
},
{
"docid": "14874811",
"text": "Oxygen (O2) deprivation, or hypoxia, has profound effects on cell metabolism and growth. Cells can adapt to low O2 in part through activation of hypoxia-inducible factor (HIF). We report here that hypoxia inhibits mRNA translation by suppressing multiple key regulators, including eIF2alpha, eEF2, and the mammalian target of rapamycin (mTOR) effectors 4EBP1, p70S6K, and rpS6, independent of HIF. Hypoxia results in energy starvation and activation of the AMPK/TSC2/Rheb/mTOR pathway. Hypoxic AMP-activated protein kinase (AMPK) activation also leads to eEF2 inhibition. Moreover, hypoxic effects on cellular bioenergetics and mTOR inhibition increase over time. Mutation of the TSC2 tumor suppressor gene confers a growth advantage to cells by repressing hypoxic mTOR inhibition and hypoxia-induced G1 arrest. Together, eIF2alpha, eEF2, and mTOR inhibition represent important HIF-independent mechanisms of energy conservation that promote survival under low O2 conditions.",
"title": "Hypoxia-induced energy stress regulates mRNA translation and cell growth."
},
{
"docid": "6669242",
"text": "Although protein acetylation is widely observed, it has been associated with few specific regulatory functions making it poorly understood. To interrogate its functionality, we analyzed the acetylome in Escherichia coli knockout mutants of cobB, the only known sirtuin-like deacetylase, and patZ, the best-known protein acetyltransferase. For four growth conditions, more than 2,000 unique acetylated peptides, belonging to 809 proteins, were identified and differentially quantified. Nearly 65% of these proteins are related to metabolism. The global activity of CobB contributes to the deacetylation of a large number of substrates and has a major impact on physiology. Apart from the regulation of acetyl-CoA synthetase, we found that CobB-controlled acetylation of isocitrate lyase contributes to the fine-tuning of the glyoxylate shunt. Acetylation of the transcription factor RcsB prevents DNA binding, activating flagella biosynthesis and motility, and increases acid stress susceptibility. Surprisingly, deletion of patZ increased acetylation in acetate cultures, which suggests that it regulates the levels of acetylating agents. The results presented offer new insights into functional roles of protein acetylation in metabolic fitness and global cell regulation.",
"title": "Protein acetylation affects acetate metabolism, motility and acid stress response in Escherichia coli"
}
] |
3703
|
How do 'payday money' stores fund their 'buy now, pay later' loans?
|
[
{
"docid": "551009",
"text": "Payday loan companies basically are banks (although they are incredibly terrible ones). Banks make money in two ways: (1) They charge fees for services they provide (bank account fees, etc.); and (2) The interest rate differential: They borrow money from individuals and corporations (your savings account is essentially money you are loaning to the bank) for a small % paid to individuals, and then lend that money back to other people for a higher %. ie: You might earn 0.5% on your savings account, but then the bank takes that money and lends it to your neighbor for 2.5% as part of their mortgage. Payday loan companies make money in one way: They charge an enormous markup on money lent out to other people. The rates in some cases are so high (annualized interest rates of >1000% are not uncommon in countries without full regulation of this industry), that it barely matters where they get money from. They might get money from investors [who bought shares in the company, giving the company initial cash in the hope that they give dividends down the road], they might get money from other 'real' banks [who lend money just like they would lend money to any other business, with a regular interest rate], or they might have many from many other sources. They might even issue their debt publically, so that individuals could buy bonds from the company and receive a small amount of interest every year. The point is that the rates of return on the money leant by payday loan companies are so high, that the cost of where the money comes from is not terribly relevant.",
"title": ""
}
] |
[
{
"docid": "343457",
"text": "\"What could a small guy with $100 do to make himself not poor? The first priority is an emergency fund. One of the largest expenses of poor people are short-term loans for emergencies. Being able to avoid those will likely be more lucrative than an S&P investment. Remember, just like a loan, if you use your emergency fund, you'll need to refill it. Be smart, and pay yourself 10% interest when you do. It's still less than you'd pay for a payday loan, and yet it means that after every emergency you're better prepared for the next event. To get an idea for how much you'd need: you probably own a car. How much would you spend, if you suddenly had to replace it? That should be money you have available. If you think \"\"must\"\" buy a new car, better have that much available. If you can live with a clunker, you're still going to need a few K. Having said that, the next goal after the emergency fund should be savings for the infrequent large purchases. The emergency fund if for the case where your car unexpectedly gets totaled; the saving is for the regular replacement. Again, the point here is to avoid an expensive loan. Paying down a mortgage is not that important. Mortgage loans are cheaper than car loans, and much cheaper than payday loans. Still, it would be nice if your house is paid when you retire. But here chances are that stocks are a better investment than real estate, even if it's the real estate you live in.\"",
"title": ""
},
{
"docid": "265832",
"text": "I can't find the underlying legislation, but a few online resources suggest that if you contact a lender about a payment plan, they should put repayments on hold temporarily: http://www.financial-ombudsman.org.uk/keeps-you-awake/payday-rights.html We don’t think it’s fair if your lender: [...] Doesn’t help you get on top of things if you ask for help or “breathing space” to sort things out. https://www.citizensadvice.org.uk/debt-and-money/borrowing-money/types-of-borrowing/loans/payday-loans/payday-loans-reasons-to-complain-about-your-lender/ If you've had problems repaying the loan, you can complain if your payday lender: [...] did not offer to freeze interest and charges if you are able to make payments under a reasonable repayment plan https://www.moneyadviceservice.org.uk/en/articles/problems-paying-back-payday-loans By law, they must: [...] Suspend recovery of the debt for a reasonable period if you’re developing a repayment plan with a debt adviser or on your own I'd start by making an immediate complaint to the lender. Make them aware that you're unable to meet basic living expenses because of the money they took, and ask for them to suspend collection temporarily and for the money to be returned. I would also dispute the charge with your bank on the grounds that it should not have been taken given the circumstances, and ask for them to credit your account while they investigate the dispute. They may not be too keen given it'll leave you overdrawn if they later reject the dispute, but it's worth asking. In parallel with that, contact Citizens Advice and/or the Financial Ombudsman (details in the links) and see if there's anything they can do or suggest.",
"title": ""
},
{
"docid": "462036",
"text": "\"This may be a bit advanced now, but once you start really working and get a place, I think this will apply more... Do I set up a bank account now? Yes. There is no reason not to. As an adult you will be using this much more than you think. Assuming you have a little money, you can walk in to any bank almost any day of the week and set up an account with them in very little time. Note that they may require you to be 18 if your parents won't be with you on the account. Otherwise, just ask any bank representative to help you do this. Just to be clear, if you can get a credit union account over a typical bank account, this is a great idea. Credit unions provide exactly the same financial services as a normal bank, but typically have variety of advantages over banks. Bank Account Parts Bank accounts typically have two parts, a checking account and a savings account. Your checking account typically is what you use for most day-to-day transactions and your savings account is generally used for, well, saving money. Having a bank account often gives you the following advantages: They give you an ability to store money without having large amounts of cash on hand. Once you start working regularly, you'll find you won't want to keep ~$600+ cash every two weeks in your wallet or apartment. They help you pay bills. When you set up your bank account, you will likely be able to get a Visa debit card which will process like a regular credit card but simply deduct funds from your checking account. You can use this card online to pay utilities (i.e. electricity and water), general bills (e.g. your cell phone and cable), purchase items (ex. at Amazon) or use it in stores to pay in lieu of cash. Be aware -- some banks will give you an ATM-only card before they send you the Visa debit card in the mail. This ATM-only card can only be used at ATMs as it's name implies. Similarly, if you can invest about ~$200 to build your credit, you can often get a deposit secured credit card attached to your account (basically a credit card where the bank keeps your money in case you can't pay your bill). If you treat this card with responsibility, you can eventually transition to an unsecured credit card. They save you hassles when cashing your check. If you don't have a bank where you can cash your check (e.g. you don't have an account), you will likely be charged check cashing fees (usually by places such as grocery stores or payday loan chains, or even other banks). Furthermore, if your check is over a certain amount, some places may refuse to cash your check period and a bank may be your only option. They give you a way to receive money electronically. The most common example of this is direct deposit. Many employers will send your money directly to your bank account instead of requiring you to cash a check. If they are prompt, this money gets to you faster and saves you trouble (on payday, you'll just receive a pay stub detailing your wages and the amount deposited rather than a check). Also, since you asked about taxes, you should know that when you do eventually file with the IRS, they have an option to receive your tax refund electronically as well (e.g. direct deposit into your bank account) and that can literally save you months in some cases depending on when you file your return and how many paper checks they have to process. Does it cost money to setup? It depends. Some banks have special offers, some don't. Most places will set up an account for free, but may require a minimum deposit to open the account (typically $50-$100). The Visa debit card mentioned above generally comes free. If you want a secured credit card as above, you will want about an additional $200 (so $250 - $300 total). Note that this is absolutely NOT required. You can exclusively use the Visa debit card above if you wish. Bank Account Fees Any fees charged when you have a bank account are usually minor anymore. Regardless, the bank will hand you a whole bunch of paperwork (mostly in legalese) detailing exactly how your account works. That said, the bank person helping set things up will cover what you need to know about keeping the account in plain English. The most common types of fee associated with a bank account are monthly maintenance fees and overdraft fees, but these aren't always necessarily charged. Likewise, there may be some other fees associated with the account but these vary from bank to bank. Monthly Maintenance Fees To give some examples... Overdraft Fees Overdraft fees are typically charged when you attempt to spend more money than you have in your bank account and the bank has to cover these charges. Overdraft fees typically apply to using paper checks (which it is unlikely you will be using), but not always. That said, it is very unlikely you will be charged overdraft fees for three reasons: Many banks have done away with these fees in lieu of other ways of generating revenue. Banks that still charge these fees usually have \"\"overdraft protection\"\" options for a little more money a month, effectively negating the possibility you will be charged these fees. The ability to deduct an amount of money from your checking account is now typically checked electronically before the payment is authorized. That is, using a Visa debit card, the card balance is checked immediately, and even when using paper check, most retailers have check scanning machines that do roughly the same thing. On a personal note, the bank that I have allows my account to be deducted below my checking account balance only if the payment is requested electronically (e.g. someone who has my card information charges me for a monthly service). In this case, the funds are simply listed in the negative and deducted from any amount I deposit till the proper amount is repaid (e.g. if I'm at -$25 dollars due to a charge when my account balance was $0 and then I deposit $100, my available balance will then be $75, not $100). Finally, per the comment by @Thebluefish, while I minimize the likelihood you will be charged overdraft fees, it is good to check into the exact circumstances under which you might be charged unexpectedly by your bank. Read the documentation they give you carefully, including any mailed updates, and you'll reduce the chance of receiving a nasty surprise. For reference, here are some of the fees charged by Bank of America. What about taxes? When you begin working, an employer will usually have you fill out a tax form such as a W-4 Employee's Withholding Allowance Certificate so that your employer can withhold the correct federal income tax from your wages. If they don't, then it is your responsibility to calculate and file your own income taxes (if you are self-employed, an independent contractor or paid under the table). If your employer is reputable, they will send you additional information (generally in February) you need to properly file your taxes prior to April 15th (the IRS tax deadline for most people). This additional information will likely be some variation of a W-2 Wage and Tax Statement or possibly a Form 1099-MISC. Do I have to worry about money in my bank account? Unless you have a significant amount in your bank savings account earning interest (see \"\"Should I save for the future?\"\" below), you won't have to pay any sort of tax on money in your bank account. If you do earn enough taxable interest, the bank will send you the proper forms to file your taxes. How do I file taxes? While it won't apply till next year, you will likely be able to fill out a Form 1040EZ Income Tax Return for Single and Joint Filers With No Dependents, as long as you don't have any kids in the meantime. ;-) You will either mail in the paper form (available at your local IRS office, post office, public library, etc.) or file electronically. There will be a lot of information on how to do this when the time comes, so don't worry about details just yet. Assuming your all paid up on your taxes (very likely unless you get a good paying job and take a lot of deductions throughout the year on your W-4), you'll probably get money back from the IRS when you file your tax return. As I mentioned above, if you have a bank account, you can opt to have your refund money returned electronically and get it much sooner than if you didn't have a bank account (again, possibly saving you literal months of waiting). Should I save for my future? If so, how much? Any good articles? Yes, you should save for the future, and start as soon as possible. It's outside the scope of this answer, but listen to your Economics professor talk about compound interest. In short, the later you start saving, the less money you have when you retire. Not that it makes much difference now, but you have to think that over 45 years of working (age 20-65), you likely have to have enough money for another 20+ years of not working (65-85+). So if you want $25,000 a year for retirement, you need to make ~$50,000 - $75,000 a year between your job and any financial instruments you have (savings account, stocks, bonds, CDs, mutual funds, IRAs, job retirement benefits, etc.) Where you should stick money your money is a complicated question which you can investigate at length as you get older. Personally, though, I would recommend some combination of IRA (Individual Retirement Account), long term mutual funds, and some sort of savings bonds. There is a metric ton of information regarding financial planning, but you can always read something like Investing For Dummies or you can try the Motley Fool's How To Invest (online and highly recommended). But I'm Only 17... So what should you do now? Budget. Sounds dumb, but just look at your basic expenses and total them all up (rent, utilities, phone, cable, food, gas, other costs) and divide by two. Out of each paycheck, this is how much money you need to save not to go into debt. Try to save a little each month. $50 - $100 a month is a good starting amount if you can swing it. You can always try to save more later. Invest early. You may not get great returns, but you don't need much money to start investing. Often you can get started with as little as $20 - $100. You'll have to do research but it is possible. Put money in your savings account. Checking accounts do not typically earn interest but money in savings accounts often do (that is, the bank will actually add money to your savings assuming you leave it in there long enough). Unfortunately, this rate of interest is only about 3.5% on average, which for most people means they don't get rich off it. You have to have a significant amount of money ($5,000+) to see even modest improvements in your savings account balance each month. But still, you may eventually get there. Get into the habit of putting money places that make you money in the long run. Don't go into debt. Don't get payday loans, pawn items, or abuse credit cards. Besides wrecking your credit, even a small amount of debt ($500+) can be very hard to break out of if you don't have a great paying job and can even make you homeless (no rent means no apartment). Remember, be financially responsible -- but assuming your parents aren't totally tight with money, don't be afraid to ask for cash when you really need it. This is a much better option than borrowing from some place that charges outrageous interest or making your payments late. Have an emergency account. As already mentioned in another excellent answer, you need to have money to \"\"smooth things out\"\" when you encounter unexpected events (your employer has trouble with your check, you have to pay for some sort of repair bill, you use more gas in your car in a month than normal, etc.) Anywhere from $200 - $2000+ should do it, but ideally you should have at least enough to cover a month of basic expenses. Build good credit. Avoid the temptation to get a lot of credit cards, even if stores and banks are dying to give them to you. You really only need one to build good credit (preferably a secured one from your bank, as mentioned above). Never charge more than you can pay off in a single month. Charging, then paying that amount off before the due date on your next statement, will help your credit immensely. Likewise, pay attention to your rent, utilities and monthly services (cell phone, cable, etc.). Even though these seem like options you can put off (\"\"Oh my electric bill is only $40? I'll pay that next month...\"\") late payments on all of these can negatively affect your credit score, which you will need later to get good loans and buy a house. Get health insurance. Now that the Affordable Care Act (ACA a.k.a Obamacare) has been enacted, it is now simpler to get health insurance, and it is actually required you have some. Hopefully, your employer will offer health coverage, you can find reasonably priced coverage on your own, or you live in a state with a health exchange. Even if you can't otherwise get/afford insurance, you may qualify for some sort of state coverage depending on income. If you don't have some sort of health insurance (private or otherwise), the IRS can potentially fine you when you file your taxes. Not to be too scary, but the fine as currently proposed is jumping up to about $700 for individuals in 2016 or so. So... even if you don't grab health insurance (which you absolutely should), you need to save about $60 a month, even if just for the fine. This answer turned out a bit longer than intended, but hopefully it will help you a little bit. Welcome to the wonderful world of adult financial responsibility. :-)\"",
"title": ""
},
{
"docid": "249006",
"text": "\"This summer I used a loan from my 401(k) to help pay for the down payment of a new house. We planned on selling a Condo a few months later, so we only needed the loan for a short period but wanted to keep monthly payments low since we would be paying two mortgages for a few months. I also felt like the market might take a dip in the future, so I liked the idea of trying to cash out high and buy back low (spoiler alert: this didn't happen). So in July 2017 I withdrew $17,000 from my account (Technically $16,850.00 principal and $150 processing fee) at an effective 4.19% APR (4% rate and then the fee), with 240 scheduled payments of $86.00 (2 per month for 10 years). Over the lifetime of the loan the total finance charge was $3,790, but that money would be paid back into my account. I was happy with the terms, and it helped tide things over until the condo was sold a few months later. But then I decided to change jobs, and ended up having to pay back the loan ~20 weeks after it was issued (using the proceeds from the sale of the condo). During this time the market had done well, so when I paid back the funds the net difference in shares that I now owned (including shares purchased with the interest payments) was $538.25 less than today's value of the original count of shares that were sold to fund the loan. Combined with the $150 fee, the overall \"\"cost\"\" of the 20 week loan was about 4.05%. That isn't the interest rate (interest was paid back to my account balance), but the value lost due to the principal having been withdrawn. On paper, my account would be worth that much more if I hadn't withdrawn the money. Now if you extrapolate the current market return into 52 weeks, you can think of that loan having an APR \"\"cost\"\" of around 10.5% (Probably not valid for a multi year calculation, but seems accurate for a 12 month projection). Again, that is not interest paid back to the account, but instead the value lost due to the money not being in the account. Sure, the market could take a dip and I may be able to buy the shares back at a reduced cost, but that would require keeping sizable liquid assets around and trying to time the market. It also is not something you can really schedule very well, as the loan took 6 days to fund (not including another week of clarifying questions back/forth before that) and 10 day to repay (from the time I initiated the paperwork to when the check was cashed and shares repurchased). So in my experience, the true cost of the loan greatly depends on how the market does, and if you have the ability to pay back the loan it probably is worth doing so. Especially since you may be forced to do so at any time if you change jobs or your employment is terminated.\"",
"title": ""
},
{
"docid": "516444",
"text": "\"I'd like to suggest a plan. First, I know you want to buy a house. I get that, and that is an awesome goal to work for. You need to really sit down and decide why you want a house. People often tell we that they want a house because they are throwing their money away renting. This is just not true. There is a cost of renting, that is true, but there is also a cost of owning. There are many things with a house that you will have to pay for that will add little or no equity/value. Now that equity is nice to have, but make no mistake under no circumstance does every dime you put into your house increase its value. This is a huge misconception. There is interest, fees, repairs, taxes, and a bunch of other stuff that you will spend money on that will not increase the value of your home. You will do no harm, waiting a bit, renting, and getting to a better place before you buy a house. With that out of the way, time for the plan. Note: I'm not saying wait to buy a house; I am saying think of these as steps in the large house buying plan. Get your current debt under control. Your credit score doesn't suck, but it's not good either. It's middle of the road. Your going to want that higher if you can, but more importantly than that, you want to get into a pattern of making debt then honoring it. The single best advise I can give you is what my wife and I did. Get a credit card (you have one; don't get more) and then get into a habit of not spending more on that credit card than you actually have in the bank. If you have $50 in the bank, only spend that on your credit card. Then pay it in full, 100%, every payday (twice a month). This will improve your score quite a bit, and will, in time, get you in the habit of buying only what you can afford. Unless there has been an emergency, you should not be spending more on credit than you actually have. Your car loan needs to get under control. I'm not going to tell you to pay it off completely, but see point 2. Your car debt should not be more than you have in the bank. This, again is a credit building step. If you have 7.5k in the bank and own 7.5k on your car, your ability to get a loan will improve greatly. Start envelope budgeting. There are many systems out there, but I like YNAB a lot. It can totally turn your situation around in just a few months. It will also allow you to see your \"\"house fund\"\" growing. Breaking Point So far this sounds like a long wait, but it's not. It also sounds like I am saying to wait to actually buy a house, and I'm not. I am not saying get your debt to 0, nor do I think you should wait that long. The idea is that you get your debt under control and build a nice solid set of habits to keep it under control. A look at your finances at this point Now, at this point you still have debt, but your credit cards are at 0 and have been, every payday for a few months. Your car loan still exists, but you have money in the bank to cover this debt, and you could pay it off. It would eat your nest egg, but you could. You also have 15k set aside, just for the house. As you take longer looking for that perfect house, that number keeps growing. Your bank account now has over $25,000 in it. That's a good feeling on its own, and if you stick with your plan, buy your house and put down $15k, you still have plenty of wiggle room between credit cards that are not maxed out, and a $7.5k \"\"padding\"\" in case the roof falls in. Again it sounds like I'm saying wait. But I'm not, I'm saying plan better. All of these goals are very doable inside one year, a rough year to be sure, but doable. If you want to do it comfortably, then take two years. In that time you're looking, searching and learning.\"",
"title": ""
},
{
"docid": "494583",
"text": "\"The big difference is that you get your money earlier at the start. Suppose you start on a random day with payday on the last day of the month (monthly), or on every 2nd wednesday (biweekly), and it takes 3 days for payroll to \"\"ramp up\"\" (ie, if payday is within 3 days on your start date, your next paycheck is not on the next payday, but on the one after). If we assume every month has 30 days (to keep things simple), it is an average of 4+5+...+33 days until you get your first paycheck with monthly pay, an average of 18.5 days. For weekly it is a bit trickier Assuming you get hired at a random date here, with * being a paydate: time until you get paid: an average of 10.5 days. So you get your first pay an average of 8 days earlier. Later on, that 3 day thing no longer occurs, and now the company holds an average of 6.5 days of your pay \"\"due to you\"\" with biweekly paychecks, and about 14.5 days with weekly paychecks if you have monthly pay. So with monthly pay, on average your bank account has 8 fewer days of your pay in it at all times. This happens when you are first hired, and persists over the length of your employment. Now suppose you save that extra money (on average): Suppose you have an investment at 4% (after inflation). Over 40 years those 8 days of pay invested at 4% grow to 38 days of pay, a free month. What more, if the company has problems making payroll, you'll get a warning (to, say, look for another job) an average of 8 days sooner, and/or have the money in your account. Having someone owe you money is usually worse than having the money in your bank account.\"",
"title": ""
},
{
"docid": "217322",
"text": "\"A bank is a technology that allows society to consume now at the expense of later. Think about it this way: to consume later at the expense of now, all you have to do is save your stuff. If you want to eat pizza in a year, you can buy a bunch of pizza now, freeze it, then eat it a year later. Or you can hide money under your mattress now, and buy pizza a year later from now. But what if you want to eat pizza now, but you don't have the money to buy it? Well, you're stuck. There's no time travel: you can't go into the future and get resources from your future self to buy the pizza now with! Well, you could go to your wealthy friend who has a lot of pizza, and say, hey, if you give me pizza/money now, I will pay you back with more later! Except then your ability to get pizza/money depends on the whims of some really wealthy people who may not like you. And what if your wealthy friend really wants to keep all of his pizza? There is nothing you can do to get it now. A bank is an entity that can provide the resources/purchasing power for you to get your pizza now *without anyone in the economy eating less now as a result*. It does this via what is known as \"\"Fractional Reserve Banking,\"\" which is pretty simple. I borrow $100 from person A, keep $10 in reserve, then lend the remaining $90 to person B, who deposits it back into his bank. I keep $9 of person B's deposit in reserve, then lend $89 to person C, who deposits it in the bank, and so on and so forth. The total amount of purchasing power I can create is $1000 out of the initial $100 I borrowed from person A. As long as all my depositors don't all try to get their money out at once, society can essentially \"\"cheat time\"\" by pretending there is $1000 in existence when in reality there is only $100. Thus I have increased the purchasing power of the economy now at the expense of later (when the loans have to be repaid), and no one has to stop consuming now for me to do it! Note that this is not the typical academic answer. Neoclassical economists will say that banks are \"\"mere intermediaries\"\" between savers and borrowers. They are wrong. Banks provide the ability to consume now at the expense of later *even if no one in society is saving now*. That means when there is lots of lending going on, that we have an economic boom. But when there is little to no lending going on, and people are paying back their debts, we don't have as much (if any) growth.\"",
"title": ""
},
{
"docid": "510810",
"text": "Ok so apple doesn't store money over seas because we now have a no loophole 25% tax. You're so smart, this benefits anyone how? Now they're magically going to build factories because they pay the exact same in taxes it's just not over seas? They're going to pay more to their employees? How much did intel pull in 15b? What are they going to do now that they save a few billion or pay the same? Sorry but if you don't do anything now you won't later on.",
"title": ""
},
{
"docid": "444941",
"text": "\"This election only applies to payments that you make within 120 days of your having received loan money. These wouldn't be required payments, which is why they are called \"\"early\"\" payments. For example, let's say that you've just received $10,000 from your lender for a new loan. One month later, you pay $500 back. This election decides how that $500 will be applied. The first choice, \"\"Apply as Refund,\"\" means that you are essentially returning some of the money that you initially borrowed. It's like you never borrowed it. Instead of a $10,000 loan, it is now a $9,500 loan. The accrued interest will be recalculated for the new loan amount. The second choice, \"\"Apply as Payment,\"\" means that your payment will first be applied to any interest that has accrued, then applied to the principal. While you are in school, you don't need to make payments on student loans. However, interest is accruing from the day you get the money. This interest is simple interest, which means that the interest is only based on the loan principal; the interest is not compounding, and you are not paying interest on interest. After you leave school and your grace period expires, you enter repayment, and you have to start making payments. At this point, all the interest that has accrued from the time you first received the money until now is capitalized. This means that the interest is added to your loan principal, and interest will now be calculated on this new, larger amount. To avoid this, you can pay the interest as you go before it is capitalized, which will save you from having to pay even more interest later on. As to which method is better, just as they told you right on the form, the \"\"Apply as Refund\"\" method will save you the most money in the long run. However, as I said at the beginning, this election only applies if you make a payment within 120 days from receiving loan funds. Since you are already out of school and in repayment, I don't think it matters at all what you select here. For any students reading this and thinking about loans, I want to issue a warning. Student loans can ruin people later in life. If you truly feel that taking out a loan is the only way you'll be able to get the education you need, minimize these as much as possible. Borrow as little as possible, pay as much as you can as early as you can, and plan on knocking these out ASAP. Great Lakes has a few pages that discuss these topics:\"",
"title": ""
},
{
"docid": "173163",
"text": "Get a credit card is NOT the answer. The reason people have a bad (or no) credit score is often because they're new to the country, have just turned 18, have previously fallen into arrears or are just bad with money. Getting a credit card is risky because, if you don't stay on top of your payments, it'll just damage your score even more. Now, it sounds like I hate credit cards - but I don't, and they do have their benefits. But avoid them if possible because they can be more hassle than they're worth (ie, paying the credit back on-time, cancelling accounts when the interest comes in, moving money in and out of accounts). It's risky borrowing money from anywhere whether it's a payday lender, a bank, a credit card, etc., so use them as a last resort. If you've got your own income then that's amazing!, try not to live outside of your means and your credit score will look after (and increase) itself. It takes time to build a good credit score, but always make sure you pay the people you owe on time and the full amount. I'd stick with paying your phone provider (and any other direct debits you have setup) and avoid getting a credit card. I'd recommend Noddle to keep track of your credit score and read their FAQ on how to help build it. Unlike Experian, it's free forever so not quite as detailed... but Noddle are owned by CallCredit - one of the biggest Credit Reference Agencies in the UK so they should have the latest information on yourself. In conclusion, if you already have financial commitments like a mobile phone bill, gym membership, store cards, anything that gets paid monthly by direct debit... your credit score will increase (provided you pay the full-amount on time). I hope this helps. PS. I don't work for any of the companies here, but I've been working in the finance sector (more specifically, short-term loans) for 3+ years now.",
"title": ""
},
{
"docid": "90927",
"text": "Hard to give an answer without knowing more details (interest rates, remaining principle on loans, especially how soon the new roof is needed). Maintaining the value in your home (unless you are planning to walk away from it or short-sell or something) is of paramount importance, and the cost of a leak should it happen can be substantial. If the roof is a few years out, and you have loans with interest rates about oh I'd say around 6%or more then I would pay off those loans and take the money you were paying there and start putting it into a fund to pay for the roof. I am also a huge fan of doing whatever you can to max out your 401K contributions. Money put into a 401K early has a LOT more value than money put in later, and since you don't pay taxes on it, the cost out of your pocket is much lower (eg. at a 20% tax rate it costs you only $80 out of pocket to put $100 into your 401.. (look at that, you just made like 25% return on that $80) Paying off loans is pretty much equivalent to making a risk free return on the money equal to the interest rate on the loan. But to REALLY make that work, what you need to do is in a virtual sense, keep making the loan payment just now pay it to yourself, putting that money into a savings account, or towards your 401K or whatever. If you just torn around and start spending that money, then you are not really getting as much value to paying off the loan early.",
"title": ""
},
{
"docid": "30324",
"text": "\"The time value of money is very important in understanding this issue. Money today is worth more than money next year, two years from now, etc. It's a well understood economics concept, and well worth reading about if you have some, well, time. Not only is money literally worth more now than later due to inflation, but there is the simple fact that, assuming you have money for the purpose of doing something, being able to do that thing today is better than doing that same thing tomorrow. \"\"A bird in the hand is worth two in the bush\"\" gets to this rather directly; having it now is better than probably having it later. Would you rather have a nice meal tonight, or eat beans and rice tonight and then have the same nice meal next year? That's why interest exists, in part: you're offered some money now, for more money later; or in the case of buying a bond, you're offered more money later for some money now. The fact that people have different discount rates for money later is why the loan market can exist: people with more money than they can use now have a lower discount for future money than people who really need money right now (to buy a house, to pay their rent, whatever). So when choosing to buy a bond, you look at the money you're going to get, both over the short term (the coupon rate) and the long term (the face value), and you consider whether $80 now is worth $100 in 20 years, plus $2 per year. For some people it is - for some people it isn't, and that's why the price is as it is ($80). Odds are if you have a few thousand USD, you're probably not going to be interested in this - or if you have a very long term outlook; there are better ways to make money over that long term. But, if you're a bank needing a secure investment that won't lose value, or a trust that needs high stability, you might be willing to take that deal.\"",
"title": ""
},
{
"docid": "379445",
"text": "\"The fundamental concept of the time value of money is that money now is worth more than the same amount of money later, because of what you can do with money between now and later. If I gave you a choice between $1000 right now and $1000 in six months, if you had any sense whatsoever you would ask for the money now. That's because, in the six months, you could use the thousand dollars in ways that would improve your net worth between now and six months from now; paying down debt, making investments in your home or business, saving for retirement by investing in interest-bearing instruments like stocks, bonds, mutual funds, etc. There's absolutely no advantage and every disadvantage to waiting 6 months to receive the same amount of money that you could get now. However, if I gave you a choice between $1000 now and $1100 in six months, that might be a harder question; you will get more money later, so the question becomes, how much can you improve your net worth in six months given $1000 now? If it's more than $100, you still want the money now, but if nothing you can do will make more than $100, or if there is a high element of risk to what you can do that will make $100 that might in fact cause you to lose money, then you might take the increased, guaranteed money later. There are two fundamental formulas used to calculate the time value of money; the \"\"future value\"\" and the \"\"present value\"\" formulas. They're basically the same formula, rearranged to solve for different values. The future value formula answers the question, \"\"how much money will I have if I invest a certain amount now, at a given rate of return, for a specified time\"\"?. The formula is FV = PV * (1+R)N, where FV is the future value (how much you'll have later), PV is the present value (how much you'll have now), R is the periodic rate of return (the percentage that your money will grow in each unit period of time, say a month or a year), and N is the number of unit periods of time in the overall time span. Now, you asked what \"\"compounding\"\" is. The theory is very simple; if you put an amount of money (the \"\"principal\"\") into an investment that pays you a rate of return (interest), and don't touch the account (in effect reinvesting the interest you earn in the account back into the same account), then after the first period during which interest is calculated and paid, you'll earn interest on not just the original principal, but the amount of interest already earned. This allows your future value to grow faster than if you were paid \"\"simple interest\"\", where interest is only ever paid on the principal (for instance, if you withdrew the amount of interest you earned each time it was paid). That's accounted for in the future value formula using the exponent term; if you're earning 8% a year on your investment, then after 1 year you'll have 108% of your original investment, then after two years you'll have 1.082 = 116.64% (instead of just 116% which you'd get with simple interest). That .64% advantage to compounding doesn't sound like much of an advantage, but stay tuned; after ten years you'll have 215.89% (instead of 180%) of your original investment, after 20 you'll have 466.10% (instead of 260%) and after 30 your money will have grown by over 1000% as opposed to a measly 340% you'd get with simple interest. The present value formula is based on the same fundamental formula, but it's \"\"solved\"\" for the PV term and assumes you'll know the FV amount. The present value formula answers questions like \"\"how much money would I have to invest now in order to have X dollars at a specific future time?\"\". That formula is PV = FV / (1+R)N where all the terms mean the same thing, except that R in this form is typically called the \"\"discount rate\"\", because its purpose here is to lower (discount) a future amount of money to show what it's worth to you now. Now, the discount rate (or yield rate) used in these calculations isn't always the actual yield rate that the investment promises or has been shown to have over time. Investors will calculate the discount rate for a stock or other investment based on the risks they see in the company's financial numbers or in the market as a whole. The models used by professional investors to quantify risk are rather complex (the people who come up with them for the big investment banks are called \"\"quants\"\", and the typical quant graduates with an advanced math degree and is hired out of college with a six-figure salary), but it's typically enough for the average investor to understand that there is an inherent risk in any investment, and the longer the time period, the higher the chance that something bad will happen that reduces the return on your investment. This is why the 30-year Treasury note carries a higher interest rate than the 10-year T-note, which carries higher interest than the 6-month, 1-year and 5-year T-bills. In most cases, you as an individual investor (or even an institutional investor like a hedge fund manager for an investment bank) cannot control the rate of return on an investment. The actual yield is determined by the market as a whole, in the form of people buying and selling the investments at a price that, coupled with the investment's payouts, determines the yield. The risk/return numbers are instead used to make a \"\"buy/don't buy\"\" decision on a particular investment. If the amount of risk you foresee in an investment would require you to be earning 10% to justify it, but in fact the investment only pays 6%, then don't buy it. If however, you'd be willing to accept 4% on the same investment given your perceived level of risk, then you should buy.\"",
"title": ""
},
{
"docid": "353369",
"text": "Determine how much you are going to save first. Then determine where you can spend your money. If you're living with your parents, try to build an emergency fund of six months income. The simplest way is to put half of your income in the emergency fund for a year. Try to save at least 10% of your income for retirement. The earlier you start this, the longer you'll have to let the magic of compounding work on it. If your employer offers a 401k with a match, do that first. If not, consider an IRA. You probably want to do a Roth now (because you probably pay little in taxes so the deduction from a standard IRA won't help you). After the year, you'll have an emergency fund. Work out how much money you'll need for rent, utilities, and groceries when you're on your own. Invest that in some way. Pay off student loans if you have any. Buy a car that you can keep a long time if you need one. Go to night school. Put any excess money in a savings account or mutual fund. This is money for doing things related to housing. Perhaps you'll need to buy a washer/dryer. Or pay a down payment on a mortgage eventually. Saving this money now does two things: first, it gives you savings for when you need it; second, it keeps you from getting used to spending your entire paycheck. If you are used to only having $200 of spending cash out of each check, you will fit your spending into that. If you are used to spending $800 every two weeks, it will be hard to cut your spending to make room for rent, etc.",
"title": ""
},
{
"docid": "502686",
"text": "\"Thanks for your question. Definitely pay the car down as soon as possible (reasoning to follow). In fact, I would go even further and recommend the following: Why? 1) Make money risk free - the key here is RISK FREE. By paying down the loan now, you can avoid paying interest on the additional amount paid toward principal risk free. Imagine this scenario: if you walked into a bank and they said, \"\"If you give us $100, we'll give you $103 back today\"\", would you do it? That is exactly what you get to do by not paying interest on the remaining loan principal. 2) The spread you might make by investing is not as large as you may think. Let's assume that by investing, you can make a market return of 10%. However, these are future cash flows, so let's discount this for inflation to a \"\"real\"\" 8% return. Then let's assume that after fees and taxes this would be a 7% real after-tax return. You also have to remember that this money is at risk in the market and may not get this return in some years. Assuming that your friend's average tax rate on earned income is 25%, this means that he'd need to earn $400 pre-tax to pay the after-tax payment of $300. So this is a 4% risk-free return after tax compared to a 7% average after tax return from the market, but one where the return is at risk. The equivalent after-tax risk-free return from the market (think T-Bills) is much lower than 7%. You are also reducing risk by paying the car loan off first in a few other ways, which is a great way to increase peace of mind. First, since cars decline in value over time, you are minimizing the possibility that you will eventually end up \"\"under water\"\" on the loan, where the loan balance is greater than the value of the car. This also gives you more flexibility in terms of being able to sell the car at any point if desired. Additionally, if the car breaks down and must be replaced, you would not need to continue making payments on the old loan, of if your friend loses his job, he would own the car outright and would not need to make payments. Finally, ideally you would only be investing in the market when you intend to leave the money there for 5+ years. Otherwise, you might need to pull money out of the market at a bad time. Remember, annual market returns vary quite a bit, but over 5-10 year periods, they are much more stable. Unfortunately, most people don't keep cars 5-10+ years, so you are likely to need the money back for another car more frequently than this. If you are pulling money out of the market every 5-10 years, you are more likely to need to pull money out at a bad time. 3) Killing off the \"\"buy now, pay later\"\" mindset will result in long-term financial benefits. Stop paying interest on things that go down in value. Save up and buy them outright, and invest the extra money into things that generate income/dividends. This is a good long-term habit to have. People also tend to be more prudent when considering the total cost of a purchase rather than just the monthly payment because it \"\"feels\"\" like more money when you buy outright. As a gut check for whether this is a good idea, here is an example that Dave Ramsey likes to use: Suppose that your friend did not have the emergency fund, and also did not have the car loan and owned the car outright. In that case, would your friend take out a title loan on the car in order to have an emergency fund? I think that a lot of people would say no, which may be a good indicator that it is wise to reduce the emergency fund in order to wipe out the debt, rather than maintaining both.\"",
"title": ""
},
{
"docid": "259517",
"text": "I heard somewhere that the average cycle for people who take out payday loans is 8 loans. Like they have to keep taking out loans to pay for the last one, and it goes around 8 times before you can get out of it. Granted that's dependent on how much you take out. I'm just wary of them now.",
"title": ""
},
{
"docid": "577479",
"text": "\"I recently moved out from my parents place, after having built up sufficient funds, and gone through these questions myself. I live near Louisville, KY which has a significant effect on my income, cost of living, and cost of housing. Factor that into your decisions. To answer your questions in order: When do I know that I'm financially stable to move out? When you have enough money set aside for all projected expenses for 3-6 months and an emergency fund of 4-10K, depending on how large a safety net you want or need. Note that part of the reason for the emergency fund is as a buffer for the things you won't realize you need until you move out, such as pots or chairs. It also covers things being more expensive than anticipated. Should I wait until both my emergency fund is at least 6 months of pay and my loans in my parents' names is paid off (to free up money)? 6 months of pay is not a good measuring stick. Use months of expenses instead. In general, student loans are a small enough cost per month that you just need to factor them into your costs. When should I factor in the newer car investment? How much should I have set aside for the car? Do the car while you are living at home. This allows you to put more than the minimum payment down each month, and you can get ahead. That looks good on your credit, and allows refinancing later for a lower minimum payment when you move out. Finally, it gives you a \"\"sense\"\" of the monthly cost while you still have leeway to adjust things. Depending on new/used status of the car, set aside around 3-5K for a down payment. That gives you a decent rate, without too much haggling trouble. Should I get an apartment for a couple years before looking for my own house? Not unless you want the flexibility of an apartment. In general, living at home is cheaper. If you intend to eventually buy property in the same area, an apartment is throwing money away. If you want to move every few years, an apartment can, depending on the lease, give you that. How much should I set aside for either investment (apartment vs house)? 10-20K for a down payment, if you live around Louisville, KY. Be very choosy about the price of your house and this gives you the best of everything. The biggest mistake you can make is trying to get into a place too \"\"early\"\". Banks pay attention to the down payment for a good reason. It indicates commitment, care, and an ability to go the distance. In general, a mortgage is 30 years. You won't pay it off for a long time, so plan for that. Is there anything else I should be doing/taking advantage of with my money during this \"\"living at home\"\" period before I finally leave the nest? If there is something you want, now's the time to get it. You can make snap purchases on furniture/motorcycles/games and not hurt yourself. Take vacations, since there is room in the budget. If you've thought about moving to a different state for work, travel there for a weekend/week and see if you even like the place. Look for deals on things you'll need when you move out. Utensils, towels, brooms, furniture, and so forth can be bought cheaply, and you can get quality, but it takes time to find these deals. Pick up activities with monthly expenses. Boxing, dancing, gym memberships, hackerspaces and so forth become much more difficult to fit into the budget later. They also give you a better credit rating for a recurring expense, and allow you to get a \"\"feel\"\" for how things like a monthly utility bill will work. Finally, get involved in various investments. A 401k is only the start, so look at penny stocks, indexed funds, ETFs or other things to diversify with. Check out local businesses, or start something on the side. Experiment, and have fun.\"",
"title": ""
},
{
"docid": "62047",
"text": "\"I think this question is perfectly on topic, and probably has been asked and answered many times. However, I cannot help myself. Here are some basics however: Personal Finance is not only about math. As a guy who \"\"took vector calculus just for fun\"\", I have learned that superior math skills do not translate into superior net worth. Personal finance is about 50% behavior. Take a look at the housing crisis, car loans, or payday lenders and you will understand that the desire to be accepted by others often trumps the math surrounding a transaction. Outline your goals What is it that you want in life? A pile of money or to retire early? What does your business look like? How much cash will you need? Do you want to own a ton of rental properties? How does all this happen (set intermediate goals). Then get on a budget A budget is a plan to spend your money in advance. Stick to it. From there you can see how much money you have to implement various goals. Are your goals to aggressive? This is really important as people have a tendency to spend more money then they have. Often times when people receive a bonus at work, they spend that one bonus on two or three times over. A budget will prevent this from happening. Get an Emergency Fund Without an emergency fund, you be subject to the financial whims of people involved in your own life and that of the broader marketplace. Once you have one, you are free to invest with impunity and have less stress in a world that deals out plenty. Bad things will happen to you financially, protect against them. The best first investments are simple: Invest in yourself. Find a way to make a very healthy income with upward mobility. Also get out and stay out of debt. These things are not sexy, but they pay off in the long run. The next best investment is also simple: Index funds. These become the bench mark for all other investments. If you do not stand a good chance of beating the S&P 500 index fund, why bother? Just dump the money in the fund and sleep well at night.\"",
"title": ""
},
{
"docid": "69623",
"text": "\"In my experience (in the US), the main draw of check-cashing businesses (like \"\"CheckN2Cash\"\" is that they will hold your check for a certain period of time. This is also known as a \"\"payday loan\"\". Rather than bringing them a check someone else has written you, you write them a check yourself, postdated, and they pay you the amount on the check less their fees, and agree not to cash the check until a future date. So if you don't have the money right now but you need it before your next payday, you visit a check-cashing business and get the money, and it'll be withdrawn from your account after your next paycheck.\"",
"title": ""
},
{
"docid": "355084",
"text": "\"Chit funds started as group of people pooling money every month and drawing a lot to determine who would get the entire funds that month. For example 5 people pool together Rs 1000/- on first month person \"\"A\"\" gets the draw and takes the Rs 5000/-. Next month again same set of people pool Rs 1000/-, the person who got the money last month is removed from the list and again a draw is made. Thus everyone pays Rs 1000/- for 5 month and gets back Rs 5000/- some sooner and some later. This was done more to buy big ticket purchases, or group of ladies getting together. There is always a leader who would ensure that everyone pays and manages the process. In more business oriented chit fund, unknown people come together and contribute Rs 1000/-. There is a organiser who is a local strong man who runs this and ensures that everyone pays. The variation here is that every month instead of a lucky draw, you can buy for discount. Say this month you need the money badly, you are willing to take only Rs 4800/-, there maybe some one who is more desperate and may say he is OK with only Rs 4600/-. The balance Rs 400 is distributed amongst the other 4 members. Thus the other who had contributed Rs 5000/- over 5 months now get Rs 100 more. The next month this person is eliminated from bidding, and others 4 can bid for Rs 5000 or less. The balance is again re-distributed amongst others. This is typically run by people who do not get loans at good rates from bank and essentially borrow outside the financial industry. The people who are part of this most of the times make good returns / better than banks. But this entire industry is unregulated and hence the Strong man can dupe you, there are cases where people who take the first shot at money vanish without trace. Every city has quite a few of such funds running. It is advisable you do not indulge in such funds.\"",
"title": ""
},
{
"docid": "175019",
"text": "You are neglecting a few very important things around real estate transactions in Belgium So in the end a 300K building may cost you more than 340K, let's take some unexpected costs into account and use 350K for remainder of calculation. Even worse if it's newly built (which I doubt) the first percentage is 21% (VAT) instead of 10%. All these costs can be checked on the useful site www.hoeveelkostmijnhuis.be Now, aside from that most banks will and actually have to demand you pay part of all this yourself. So you can't do 5*60K (or 5*70K now). Mostly banks will only finance up to about 90% of the value of the building, so 90% of 300K, which is 270K (5*54K), the other 80K (5*16K) you have to pay yourselves. But it could be the bank goes as low as 80%. Another part to complicate the loan is how much you can pay a month. Since the mortgage crisis they're very strict on this. There are lots of banks that will not allow you to make monthly payments of more than 33% of your monthly income when you are going to live there. This is a nuisance even when buying one house, you want to buy 2. Odds seem low they'll accept high monthly payments because you either need an additional loan or need to pay rent, so don't count on a 5y deal. Now this is all based on a single loan, it will probably be a bit different with multiple loans. However, it is unlikely any bank will accept this, even if all loans are with the same bank. You need to consider the basics of a real-estate loan: A bank trusts you can pay it off and if not they can seize the real-estate hoping to regain their initial investment. It's very hard to seize a complete asset if only one out of 5 loan-takers defected. You could maybe do this with another less restrictive/higher risk type of loan but rates will be a lot higher (think 5-6% instead of 1.5%). And don't underestimate the running costs: for that price and 5 rooms in that city you're likely looking at an older building. Expect lots of cost for maintenance and keeping the building according to code. Also expect costs for repairs (you rent to students...). You'll also have to pay quite a bit of money on insurances and of course on real estate taxes (which are average in Ghent). Also factor in that currently there is not a housing shortage for Ghent students so you might not always have a guaranteed occupation. Also take into account responsibility: if a fire breaks out or the house collapses or a gas leak occurs, you might be sued. It doesn't matter if you're at fault, it's costly and a big nuisance. Simply because you didn't think of any of this: don't do this. It's better to invest in real estate funds. But if you still think you can do better then all the landlords Ghent is riddled with, don't do it as a personal investment. Create a BVBA, put some investment in here (like 10-20K each), approach a bank with a serious business plan to get the rest of the money as a loan (towards a single entity - your BVBA) and get things going. When the money comes in you can either give yourselves a salary or pay out profits on the shares. You may be confused about how rich you can become because we as a nation tend to overestimate the profitability of real estate. It's really not that much better than other investments (otherwise everybody would only invest in real estate funds). There are a few things that skew our vision however:",
"title": ""
},
{
"docid": "79083",
"text": "\"All right, I will try to take this nice and slow. This is going to be a little long; try to bear with me. Suppose you contribute $100 to your newly opened 401(k). You now have $100 in cash and $0 in mutual funds in your 401(k) (and $100 less than you used to somewhere else). At some later date, you use that money within the 401(k) to buy a single share of the Acme World All-Market Index Fund which happens to trade at exactly $100 per share on the day your purchase goes through. As a result, you have $0 in cash and exactly one share of that fund (corresponding to $100) within your 401(k). Some time later, the price of the fund is up 10%, so your share is now worth $110. Since you haven't contributed anything more to your 401(k) for whatever reason, your cash holding is still $0. Because your holding is really denominated in shares of this mutual fund, of which you still have exactly one, the cash equivalent of your holding is now $110. Now, you can basically do one of two things: By selling the share, you protect against it falling in price, thus in a sense \"\"locking in\"\" your gain. But where do you put the money instead? You obviously can't put the money in anything else that might fall in price; doing so would mean that you could lose a portion of your gains. The only way to truly \"\"lock in\"\" a gain is to remove the money from your investment portfolio altogether. Roughly speaking, that means withdrawing the money and spending it. (And then you have to consider if the value of what you spent the money on can fluctuate, and as a consequence, fall. What's the value of that three weeks old jug of milk in the back of your refrigerator?) The beauty of compounding is that it doesn't care when you bought an investment. Let's say that you kept the original fund, which was at $110. Now, since that day, it is up another 5%. Since we are looking at the change of price of the fund over some period of time, that's 5% of $110, not 5% of the $100 you bought at (which was an arbitrary point, anyway). 5% of $110 is $5.50, which means that the value of your holding is now at $115.50 from a gain first of 10% followed by another 5%. If at the same day when the original fund was at $110 you buy another $100 worth of it, the additional 5% gain is realized on the sum of the two at the time of the purchase, or $210. Thus after the additional 5% gain, you would have not $210 (($100 + $100) + 5%), nor $205 (($100 + 5%) + $100), but $220.50 (($110 + $100) + 5%). See how you don't need to do anything in particular to realize the beauty of compounding growth? There is one exception to the above. Some investments pay out dividends, interest or equivalent in cash equivalents. (Basically, deposit money into an account of yours somewhere; in the case of retirement plans, usually within the same container where you are holding the investment. These dividends are generally not counted against your contribution limits, but check the relevant legal texts if you want to be absolutely certain.) This is somewhat uncommon in mutual funds, but very common in other investments such as stocks or bonds that you purchase directly (which you really should not do if you are just starting out and/or feel the need to ask this type of question). In that case, you need to place a purchase order yourself for whatever you want to invest the dividend in. If you don't, then the extra money of the dividend will not be growing along with your original investment.\"",
"title": ""
},
{
"docid": "459724",
"text": "Danger. The affidavit is a legal document. Understand the risk of getting caught. If you are planning on using the condo to generate income the chances that you default on the loan are higher than an owner occupied property. That is why they demand more down payment (20%+) and charge a higher rate. The document isn't about making sure you spend 183+ nights a year in the property, it is making sure that it isn't a business, and you aren't letting a 3rd party live in the property. If you within the first year tell the mortgage company to send the bill to a new address, or you change how the property is insured, they will suspect that it is now a rental property. What can they do? Undo the loan; ask for penalty fee; limit your ability to get a mortgage in the future; or a percentage of the profits How likely is it? The exact penalty will be in the packet of documents you receive. It will depend on which government agency is involved in the loan, and the lenders plan to sell it on the secondary market. It can also depend on the program involved in the sale of the property. HUD and sister agencies lock out investors during the initial selling period, They don't want somebody to represent themselves as homeowner, but is actually an investor. Note: some local governments are interested not just in non-investors but in properties being occupied. Therefore they may offer tax discounts to residents living in their homes. Then they will be looking at the number of nights that you occupy the house in a year. If they detect that you aren't really a resident living in the house, that has tax penalties. Suggestion: If you don't want to wait a year buy the condo and let the loan officer know what your plan is. You will have to meet the down payment and interest rate requirements for an investment property. Your question implies that you will have enough money to pay the required 20% down payment. Then when you are ready buy the bigger house and move in. If you try and buy the condo with a non-investment loan you will have to wait a year. If you try and pay cash now, and then get a home equity loan later you will have to admit it is a rental. And still have to meet the investor requirements.",
"title": ""
},
{
"docid": "489561",
"text": "I have a car loan paid in full and even paid off early, and 2 personal loans paid in full from my credit union that don't seem to reflect in a positive way and all 3 were in good standing. But you also My credit card utilization is 95%. I have a total of 4 store credit cards, a car loan, 2 personal loans. So assuming no overlap, you've paid off three of your ten loans (30%). And you still have 95% utilization. What would you do if you were laid off for six months? Regardless of payment history, you would most likely stop making payments on your loans. This is why your credit score is bad. You are in fact a credit risk. Not due to payment history. If your payment history was bad, you'd likely rank worse. But simple fiscal reality is that you are an adverse event away from serious fiscal problems. For that matter, the very point that you are considering bankruptcy says that they are right to give you a poor score. Bankruptcy has adverse effects on you, but for your creditors it means that many of them will never get paid or get paid less than what they loaned. The hard advice that we can give is to reduce your expenses. Stop going to restaurants. Prepare breakfast and supper from scratch and bag your lunch. Don't put new expenses on your credit cards unless you can pay them this month. Cut up your store cards and don't shop for anything but necessities. Whatever durables (furniture, appliances, clothes, shoes, etc.) you have now should be enough for the next year or so. Cut your expenses. Have premium channels on your cable or the extra fast internet? Drop back to the minimum instead. Turn the heat down and the A/C temperature up (so it cools less). Turn off the lights if you aren't using them. If you move, move to a cheaper apartment. Nothing to do? Get a second job. That will not only keep you from being bored, it will help with your financial issues. Bankruptcy will not itself fix the problems you describe. You are living beyond your means. Bankruptcy might make you stop living beyond your means. But it won't fix the problem that you make less money than you want to spend. Only you can do that. Better to stop the spending now rather than waiting until bankruptcy makes your credit even worse and forces you to cut spending. If you have extra money at the end of the month, pick the worst loan and pay as much of it as you can. By worst, I mean the one with the worst terms going forward. Highest interest rate, etc. If two loans have the same rate, pay the smaller one first. Once you pay off that loan, it will increase the amount of money you have left to pay off your other loans. This is called the debt snowball (snowball effect). After you finish paying off your debt, save up six months worth of expenses or income. These will be your emergency savings. Once you have your emergency fund, write out a budget and stick to it. You can buy anything you want, so long as it fits in your budget. Avoid borrowing unless absolutely necessary. Instead, save your money for bigger purchases. With savings, you not only avoid paying interest, you may actually get paid interest. Even if it's a low rate, paid to you is better than paying someone else. One of the largest effects of bankruptcy is that it forces you to act like this. They offer you even less credit at worse terms. You won't be able to shop on credit anymore. No new car loan. No mortgage. No nice clothes on credit. So why declare bankruptcy? Take charge of your spending now rather than waiting until you can't do anything else.",
"title": ""
},
{
"docid": "239611",
"text": "\"The most important thing in my view is flexibility, to avoid running into problems. One useful thing in the UK would be an arranged overdraft. You go to your bank, and they'll agree that you can overdraw your account by a certain number of pounds, depending on your income etc. It will cost you a very high interest rate, but only for each day where you are overdrawn. So paying a bill two days before your salary comes in isn't too bad. Obviously avoid using the overdraft if you can, having an overdraft while not using it is free. It's meant for an emergency; being regularly overdrawn is expensive. But once it is arranged with your bank, an arranged overdraft is much much cheaper than bouncing cheques etc. and possibly high fees for overdrawing your account. And it takes the pressure of you. Now things to need before you get a loan (again, UK): The real interest rate that you are paying is called APR. That's the number that counts, and that cannot be manipulated. No \"\"payday loans\"\" to avoid getting yourself into deep, deep trouble. No loan sharks, obviously. If you buy things with \"\"interest free credit\"\", that's (a) included in the price, so you pay more, and (b) if you miss paying by one day they'll hit you with huge interest payments, and some will try this intentionally. Interest rate depends on loan amount. I once had to borrow 20% more than I needed because it reduced the interest rate by half... The 20% went straight into a savings account. Credit cards and overdrafts are much more expensive than loans. Mortgage is again cheaper than a loan usually. Make sure that you only use money from sources that charge the least amount. Make sure you pay back regularly so cheap sources stay available to you. Just do yourself a favour and if at all possible, spend less instead of getting a loan.\"",
"title": ""
},
{
"docid": "92649",
"text": "\"The balance sheet for a bank is the list of assets and liabilities that the bank directly is responsible for. This would be things like loans the bank issues and accounts with the bank. Banks can make both \"\"balance sheet\"\" loans, meaning a loan that says on the balance sheet - one the bank gains the profits from but holds the risks for also. They can also make \"\"off balance sheet\"\" loans, meaning they securitize the loan (sell it off, such as the mortgage backed securities). Most major banks, i.e. Chase, Citibank, etc., could be called \"\"balance sheet\"\" banks because at least some portion of their lending comes from their balance sheet. Not 100% by any means, they participate in the security swaps extensively just like everyone does, but they do at least some normal, boring lending just as you would explain a bank to a five year old. Bank takes in deposits from account holders, loans that money out to people who want to buy homes or start businesses. However, some (particularly smaller) firms don't work this way - they don't take responsibility for the money or the loans. They instead \"\"manage assets\"\" or some similar term. I think of it like the difference between Wal-Mart and a consignment store. Wal-Mart buys things from its distributors, and sells them, taking the risk (of the item not selling) and the reward (of the profit from selling) to itself. On the other hand, a consignment store takes on neither: it takes a flat fee to host your items in its store, but takes no risk (you own the items) nor the majority of the profit. In this case, Mischler Financial Group is not a bank per se - they don't have accounts; they manage funds, instead. Note the following statement on their Services page for example: Mischler Financial Group holds no risk positions and no unwanted inventory of securities, which preserves the integrity of our capital and assures our clients that we will be able to obtain bids and offers for them regardless of adverse market conditions. They're not taking your money and then making their own investments; they're advising you how to invest your money, or they're helping do it for you, but it's your money going out and your risk (and reward).\"",
"title": ""
},
{
"docid": "481021",
"text": "Cash Advance Plus will be of use to you as long as you pay attention to how much you owe and when it is due. If you take these steps, you’ll be ready for an Eastside Lenders payday loan or a Zoom payday loan. In fact, you may find yourself feeling ready for just about anything.",
"title": ""
},
{
"docid": "285033",
"text": "\"Here I thought I would not ever answer a question on this site and boom first ten minutes. First and foremost I am in the automotive industry, specifically one of our core competencies is finance department management consulting and the sales process both for the sale of the care as well as the financial transaction. First and foremost new vehicle gross profits are nowhere near 20% for the dealership. In an entry level vehicle like say a Toyota Corolla there is only a few hundreds of dollars in markup from invoice to M.S.R.P. There is also something called holdback that dealers get for achieving certain goals such as sales volume. These are usually pretty easy to hit. As a matter of fact I have never heard of a dealer not getting the hold back on a deal. This hold back is there to cover overhead for the car, the cost of getting it ready to sell, having a lot to park it on, making it ready for delivery, offset some of the cost of sales labor etc. Most dealerships consider the holdback portion of the invoice to not be part of the deal when it comes to negotiations. Certain brands such as KIA and Chrysler have something called \"\"Dealer Cash\"\" these payouts are usually stair stepped according to volume and vary by dealer, location, past history, how the guys at the factory feel that day and any number of combinations. Then there is CSI or Customer Service Index payments, these payments are usually made every 1/4 are on the Parts Statement not the Sales Doc and while they effect the dealers bottom line they almost never affect the sales managers or sales persons payroll so they are not considered a part of the cost of the car. They are however extremely important to the dealer and this is why after you have your new car they want you to bring in your survey for a free oil change or something. IF you are going to give a bad survey they want to throw it away and not send it in, if you are going to give a good survey they want to make sure you fill it out correctly. This is because lets say they ask you on a scale of 1-10 how was your sales person and you put a 9 that is a failing score. Dumb I know but that is how every factory CSI score system I have seen worked. According to NADA the average New Vehicle gross profit including hold back and dealer cash is around $1000.00. No where near 20%. Dealerships would love it if they made 20% on your new F250 Supercrew Diesel at around $50,000.00. One last thing there is something on the invoice called Wholesale Finance Reserve. This is the amount of money the factory forwards to the Dealership to offset the cost of financing vehicle on the floor plan so they can have it for you to look at before you buy. This is usually equal to around 3 months of interest and while you might buy a vehicle that has been on the lot for 2 days they have plenty that have been there much longer so this equals out in a fair to middling run store. General Mangers that know what they are doing can make this really pad their net profit to statement. On to incentives, there are basically 3 kinds. Cash to customer in the form of rebates, Dealer Cash in the form of incentives to dealerships based on volume or the undesirability of a vehicle, and incentive rates or Subvented leases. The rates are pretty self explanatory as they advertised as such (example 0% for 60 Months). Subvented Leased are harder to figure out and usually not disclosed as they are hard to explain and also a source of increased profit. Subvented leases are usually powered by lower cost of money called a money factor (think of it as an interest rate) that is discounted from the lease company or a subsidized residual. Subsidized residuals are virtually verboten on domestic vehicles due to their poor resell values. A subsidized residual works like this, you buy a Toyota Camry and the ALG (automotive lease guide) says it has a residual at 36 months of 48%. Well Toyota Motor Credit says we will give you a subvented residual of 60% basically subsidizing a 2% increase in residual. Since they do not expect to be able to sell the car at auction for that amount they have to set aside the 2% as a future expense. What does this mean to you, it means a lower payment. Also a good rule of thumb if you are told a money factor by your salesperson to figure out what the interest rate is just multiply it by 2400. So if a money factor is give of .00345 you know your actual interest rate is a little bit lower than 8.28% (illustration purposes only money factors are much lower than that right now). So how does this save you money well a lease is basically calculated by multiplying the MSRP by the residual and then subtracting that amount from the \"\"Capitalized Cost\"\" which is the Price paid for the car - trade in + payoff + TT&L-Rebate-Down Payment. That is the depreciation. Then you divide that number by the term of the loan and you have the depreciation amount. So if you have 20K CC and 10K R your D = 10K / 36 = 277 monthly payment. For the rest of the monthly payment you add (I think been a long time since I did this with out a computer) the Residual plus the CC for $30,000 * MF of .00345 = 107 for a total payment of 404 ish. This is not completely accurate but you can use it to make sure a salesperson/finance person is not trying to do one thing and say another as so often happens on leases. 0% how the heck do they make money at that, well its simple. First in 2008 the Fed made all the \"\"Captive\"\" lenders into actual banks instead of whatever they were before. So now they have access to the Fed's discounting window which with todays monetary policies make it almost free money. In the past these lenders had to go through all kinds of hoops to raise funds and securitize loans even for super prime credit. Those days are essentially over. Now they get their short term money just like Bank of America does. Eventually they still bundle these loans and sell them. So in the short term YOU pay for the 0% by giving up part or all of your rebate. This is really important DO NOT GIVE up your rebate for 0% unless it makes sense to do so. When you can get the money at 2.5% and get a $7000.00 rebate (customer cash) on that F250 or 0% take the cash. First of all make the finance guy/gal show you the the difference in total cost they can do do this using the federal truth in lending disclosures on a finance contract. Secondly how long will you keep the vehicle? If you come out ahead by say $1500 by taking the lower rate but you usually trade out every three years this is not going to work. Also and this is important if you are involved in a situation with a total loss like a stolen car or even worse a bad wreck before the breakeven point you lose that price break. Finally on judging what is right for you, just know that future value of the vehicle on for resell or trade-in will take into effect all of these past rebates and value the car accordingly. So if a vehicle depreciates 20% a year for the first 3 years the starting point will essentially be $7000.00 less than you actually paid, using rough numbers. How does this help the dealers and car companies? Well while a dealer struggles to make money on new cars the factory makes all of their money on the new cars and the new car financing. While your individual loan might lose money that money is offset by the loss of rebate and I think Ford does actually pay Ford Motor Credit Company the difference in the rate. The most important thing is what happens later FMCC now has 2500 loans with people with perfect credit. They can now use those loans to budle with people with not so perfect credit that they financed at 12%-18% and buy that money with interest rates in the 2%-3% range. Well that is a hell of a lot of profit. 'How does it help the dealership, well the more super prime credit they have in their portfolio the more subprime credit the banks will buy for them. This means they have more loans originated that are more profitable for them. Say you come in for the 0% but have 590 credit score, they get FMCC to buy the deal because they have a good portfolio and you win because the dealer gets to buy the money at say 9% and sell it to you at say 12% making the spread. You win there because you actually qualified for a rate of around 18% with a subprime company like Santander or Capital One (yes that capital one) so you save a ton on your overall cost of the car. Any dealership that is half way well run makes as much or money in the finance and insurance office than the rest of the dealership. When you factor in what a good F&I Director can do to get deals done with favorable terms that really goes up. Think about that the guys sitting a desk drinking coffee making more than the service department guys all put together. Well that was long winded but there I broke down the car business for whoever read this far.\"",
"title": ""
},
{
"docid": "110046",
"text": "Everybody on the car title will need to participate in the selling process. The person who is buying the car will need everybody to sign the paperwork so that nobody months later tries to say they never agreed to sell the car. The money will have to be sent to the lender to pay off the rest of the loan. If the money isn't enough to pay off the loan everybody will have to decide how the extra money will be sent to the lender. This will have to be done as part of the selling process because the lender doesn't want you to sell the car and keep the cash. Once the car is gone so is the collateral and they can't take it back if you miss payments. If the cousin is too far away to participate in the selling of the car, you may need the buyer and the lender to tell you how to proceeded. If you are selling at a dealership they will know what documents and signatures will be needed, the bank will also know what to do. If the loan is almost paid off it may be easier to pay the loan first, and then get the title without the lenders name before trying to sell it.",
"title": ""
},
{
"docid": "372657",
"text": "\"Let's talk interest rates on your junk bonds. Even after all that the US has been through (and is still going through), the United States dollar is widely regarded as one of the safest safe havens for your money. As such it serves as a de facto baseline against which all other investments can be measured, the bar everyone has to pass: if you could earn 4% on a 5-year US Treasury bond, or earn 4% on anything else over the next 5 years, you pick the Treasury bond. In many ways this means that the interest rate on a Treasury bond is the closest single measure we have to the price of money all by itself. If someone is loaning you money, they could be loaning it to the Treasury instead; they are losing out by making this loan to you, and must charge you at least this rate just to break even. But most people/governments/countries aren't as credit-worthy as the US Treasury. A few are (the US treasury isn't magical, after all, just really good at what it does), but generally they are not. There is a possibility when loaning money to these entities that you will not get your money back. That is risk. All entities have some risk (even the US treasury!), and some have more than others; \"\"junk bonds\"\" have a somewhat elevated level of this risk. Now, you don't just take a risk on for free (unless you're being charitable or something, but I hope you can find better beneficiaries of charity than the average junk bond). You need to be compensated for that risk. Lenders will demand compensation commensurate with that risk - or they will just walk away without making any loans or buying any bonds because it's not worth it. The difference between the interest rate on a US Treasury bond and the interest rate on another bond, such as a junk bond, is the risk premium - the cost of carrying that risk. Therefore you can see that the interest rate on a junk bond is the price of money plus the risk premium. Now, the Federal Reserve adjusts the price of money from time to time, by buying and selling US Treasury bonds until the price is something they like. This means that one component of interest rate on a junk bond is the interest rate on the US Treasury bond, and it is effectively controlled by the Federal Reserve (through that layer of indirection). The other component of the interest rate on a junk bond is the risk premium. It's not generally possible to know in advance whether or not some company will actually default. People have to guess, and decide how comfortable they are taking that risk. This means that risk is more expensive (and interest rates are higher) when they think the companies in question are going through some hard times, and risk will also be more expensive when people decide that they can't take as many risks (perhaps they've already lost some money and need to take additional steps to protect the rest). It's definitely very hard for an individual to decide what the risk on a particular bond is. The good news is that you generally don't have to. There are a bunch of rich jerks, hedge funds, retirement funds, insurance companies, and other investment entities out there who spend all day looking at things like bonds, trying to estimate the risk. Their willingness to exploit minuscule differences between the interest rate on a bond and the real risk means that the average bond on the market will be fairly priced, according to what all those people think. Plenty of them can still be wrong, mind you (cf. mortgage-backed securities) but in the general case the price of any security reflects all the information everyone in the world has on it on average, so if you're wrong you're in good company. When you buy a nice diversified bond fund, you have access to a bunch of bonds at a pretty-standard price. So that's interest rates for you. But you asked about prices. As it turns out, they're the same thing! - just expressed slightly differently. One way or another a bond is essentially meant to be a stream of payments worth a certain amount in the end - this is why you'll hear them referred to sometimes as a \"\"fixed-income security\"\". The interest rate is essentially the difference between the price you pay now, and the value you receive later, except expressed as a rate. Technically, you could structure the bonds differently (e.g. does the bond pay little bits of interest as you go along, or just pay one big lump sum in the end?) but you can use Math to convert between these two situations, and figure out how much money is worth which when, so it doesn't really matter. Anyway. This means that rising interest rates means lower bond prices on bonds you already own (and falling interest rates means higher bond prices). So if the Federal Reserve increases interest rates, the face value of your bond funds will fall. Also, if people think that the companies issuing the bonds are too risky, the face value of those bonds will also fall. (You were probably expecting the latter effect, though.) Mind you, you will still get the same amount of future money out of them as you would otherwise: that's why they're fixed-income securities. However, a higher interest rate means \"\"I can get more money in the future for less money now\"\", and so people will be willing to pay you less for your bond in the present. This is known as interest rate risk. It is higher on longer term bonds, because those have more time to earn interest.\"",
"title": ""
}
] |
5110
|
Why does shorting a call option have potential for unlimited loss?
|
[
{
"docid": "281533",
"text": "\"You are likely making an assumption that the \"\"Short call\"\" part of the article you refer to isn't making: that you own the underlying stock in the first place. Rather, selling short a call has two primary cases with considerably different risk profiles. When you short-sell (or \"\"write\"\") a call option on a stock, your position can either be: covered, which means you already own the underlying stock and will simply need to deliver it if you are assigned, or else uncovered (or naked), which means you do not own the underlying stock. Writing a covered call can be a relatively conservative trade, while writing a naked call (if your broker were to permit such) can be extremely risky. Consider: With an uncovered position, should you be assigned you will be required to buy the underlying at the prevailing price. This is a very real cost — certainly not an opportunity cost. Look a little further in the article you linked, to the Option strategies section, and you will see the covered call mentioned there. That's the kind of trade you describe in your example.\"",
"title": ""
}
] |
[
{
"docid": "140371",
"text": "To expand on the comment made by @NateEldredge, you're looking to take a short position. A short position essentially functions as follows: Here's the rub: you have unlimited loss potential. Maybe you borrow a share and sell it at $10. Maybe in a month you still haven't closed the position and now the share is trading at $1,000. The share lender comes calling for their share and you have to close the position at $1,000 for a loss of $990. Now what if it was $1,000,000 per share, etc. To avoid this unlimited loss risk, you can instead buy a put option contract. In this situation you buy a contract that will expire at some point in the future for the right to sell a share of stock for $x. You get to put that share on to someone else. If the underlying stock price were to instead rise above the put's exercise price, the put will expire worthless — but your loss is limited to the premium paid to acquire the put option contract. There are all sorts of advanced options trades sometimes including taking a short or long position in a security. It's generally not advisable to undertake these sorts of trades until you're very comfortable with the mechanics of the contracts. It's definitely not advisable to take an unhedged short position, either by borrowing someone else's share(s) to sell or selling an option (when you sell the option you take the risk), because of the unlimited loss potential described above.",
"title": ""
},
{
"docid": "118633",
"text": "\"There are three ways to do this. So far the answers posted have only mentioned two. The three ways are: Selling short means that you borrow stock from your broker and sell it with the intent of buying it back later to repay the loan. As others have noted, this has unlimited potential losses and limited potential gains. Your profit or loss will go $1:$1 with the movement of the price of the stock. Buying a put option gives you the right to sell the stock at a later date on a price that you choose now. You pay a premium to have this right, and if the stock moves against you, you won't exercise your option and will lose the premium. Options move non-linearly with the price of the stock, especially when the expiration is far in the future. They probably are not for a beginner, although they can be powerful if used properly. The third option is a synthetic short position. You form this by simultaneously buying a put option and selling short a call option, both at the same strike price. This has a risk profile that is very much like the selling the stock short, but you can accomplish it entirely with stock options. Because you're both buying an selling, in theory you might even collect a small net premium when you open. You might ask why you'd do this given that you could just sell the stock short, which certainly seems simpler. One reason is that it is not always possible to sell the stock short. Recall that you have to borrow shares from your broker to sell short. When many people want to short the stock, brokers will run out of shares to loan. The stock is then said to be \"\"hard to borrow,\"\" which effectively prevents further short selling of the stock. In this case the synthetic short is still potentially possible.\"",
"title": ""
},
{
"docid": "307518",
"text": "\"The stock market is not a zero-sum game. Some parts are (forex, some option trading), but plain old stock trading is not zero sum. That is to say, if you were to invest \"\"at random\"\", you would on average make money. That's because the market as a whole makes money - it goes up over time (6-10% annually, averaged over time). That's because you're not just gambling when you buy a stock; you're actually contributing money to a company (directly or indirectly), which it uses to fund activities that (on average) make money. When you buy Caterpillar stock, you're indirectly funding Caterpillar building tractors, which they then sell for a profit, and thus your stock appreciates in value. While not every company makes a profit, and thus not every stock appreciates in true value, the average one does. To some extent, buying index funds is pretty close to \"\"investing at random\"\". It has a far lower risk quotient, of course, since you're not buying a few stocks at random but instead are buying all stocks in an index; but buying stocks from the S&P 500 at random would on average give the same return as VOO (with way more volatility). So for one, you definitely could do worse than 50/50; if you simply sold the market short (sold random stocks short), you would lose money over time on average, above and beyond the transaction cost, since the market will go up over time on average. Secondly, there is the consideration of limited and unlimited gains or losses. Some trades, specifically some option trades, have limited potential gains, and unlimited potential losses. Take for example, a simple call option. If you sell a naked call option - meaning you sell a call option but don't own the stock - for $100, at a strike price of $20, for 100 shares, you make money as long as the price of that stock is under $21. You have a potential to make $100, because that's what you sold it for; if the price is under $20, it's not exercised, and you just get that $100, free. But, on the other hand, if the stock goes up, you could potentially be out any amount of money. If the stock trades at $24, you're out $400-100 = $300, right? (Plus transaction costs.) But what if it trades at $60? Or $100? Or $10000? You're still out 100 * that amount, so in the latter case, $1 million. It's not likely to trade at that point, but it could. If you were to trade \"\"at random\"\", you'd probably run into one of those types of situations. That's because there are lots of potential trades out there that nobody expects anyone to take - but that doesn't mean that people wouldn't be happy to take your money if you offered it to them. That's the reason your 16.66 vs 83.33 argument is faulty: you're absolutely right that if there were a consistently losing line, that the consistently winning line would exist, but that requires someone that is willing to take the losing line. Trades require two actors, one on each side; if you're willing to be the patsy, there's always someone happy to take advantage of you, but you might not get a patsy.\"",
"title": ""
},
{
"docid": "105231",
"text": "The important thing to realize is, what would you do, if you didn't have the call? If you didn't have call options, but you wanted to have a position in that particular stock, you would have to actually purchase it. But, having purchased the shares, you are at risk to lose up to the entire value of them-- if the company folded or something like that. A call option reduces the potential loss, since you are at worst only out the cost of the call, and you also lose a little on the upside, since you had to pay for the call, which will certainly have some premium over buying the underlying share directly. Risk can be defined as reducing the variability of outcomes, so since calls/shorts etc. reduce potential losses and also slightly reduce potential gains, they pretty much by definition reduce risk. It's also worth noting, that when you buy a call, the seller could also be seen as hedging the risk of price decreases while also guaranteeing that they have a buyer at a certain price. So, they may be more concerned about having cash flow at the right time, while at the same time reducing the cost of the share losing in value than they are losing the potential upside if you do exercise the option. Shorts work in the same way but opposite direction to calls, and forwards and futures contracts are more about cash flow management: making sure you have the right amount of money in the right currency at the right time regardless of changes in the costs of raw materials or currencies. While either party may lose on the transaction due to price fluctuations, both parties stand to gain by being able to know exactly what they will get, and exactly what they will have to pay for it, so that certainty is worth something, and certainly better for some firms than leaving positions exposed. Of course you can use them for speculative purposes, and a good number of firms/people do but that's not really why they were invented.",
"title": ""
},
{
"docid": "107045",
"text": "Rich's answer captures the basic essence of short selling with example. I'd like to add these additional points: You typically need a specially-privileged brokerage account to perform short selling. If you didn't request short selling when you opened your account, odds are good you don't have it, and that's good because it's not something most people should ever consider doing. Short selling is an advanced trading strategy. Be sure you truly grok selling short before doing it. Consider that when buying stock (a.k.a. going long or taking a long position, in contrast to short) then your potential loss as a buyer is limited (i.e. stock goes to zero) and your potential gain unlimited (stock keeps going up, if you're lucky!) Whereas, with short selling, it's reversed: Your loss can be unlimited (stock keeps going up, if you're unlucky!) and your potential gain is limited (i.e. stock goes to zero.) The proceeds you receive from a short sale – and then some – need to stay in your account to offset the short position. Brokers require this. Typically, margin equivalent to 150% the market value of the shares sold short must be maintained in the account while the short position is open. The owner of the borrowed shares is still expecting his dividends, if any. You are responsible for covering the cost of those dividends out of your own pocket. To close or cover your short position, you initiate a buy to cover. This is simply a buy order with the intention that it will close out your matching short position. You may be forced to cover your short position before you want to and when it is to your disadvantage! Even if you have sufficient margin available to cover your short, there are cases when lenders need their shares back. If too many short sellers are forced to close out positions at the same time, they push up demand for the stock, increasing price and deepening their losses. When this happens, it's called a short squeeze. In the eyes of the public who mostly go long buying stock, short sellers are often reviled. However, some people and many short sellers believe they are providing balance to the market and preventing it sometimes from getting ahead of itself. [Disambiguation: A short sale in the stock market is not related to the real estate concept of a short sale, which is when a property owner sells his property for less than he owes the bank.] Additional references:",
"title": ""
},
{
"docid": "272547",
"text": "\"Ok, I think what you're really asking is \"\"how can I benefit from a collapse in the price of gold?\"\" :-) And that's easy. (The hard part's making that kind of call with money on the line...) The ETF GLD is entirely physical gold sitting in a bank vault. In New York, I believe. You could simply sell it short. Alternatively, you could buy a put option on it. Even more risky, you could sell a (naked) call option on it. i.e. you receive the option premium up front, and if it expires worthless you keep the money. Of course, if gold goes up, you're on the hook. (Don't do this.) (the \"\"Don't do this\"\" was added by Chris W. Rea. I agree that selling naked options is best avoided, but I'm not going to tell you what to do. What I should have done was make clear that your potential losses are unlimited when selling naked calls. For example, if you sold a single GLD naked call, and gold went to shoot to $1,000,000/oz, you'd be on the hook for around $10,000,000. An unrealistic example, perhaps, but one that's worth pondering to grasp the risk you'd be exposing yourself to with selling naked calls. -- Patches) Alternative ETFs that work the same, holding physical gold, are IAU and SGOL. With those the gold is stored in London and Switzerland, respectively, if I remember right. Gold peaked around $1900 and is now back down to the $1500s. So, is the run over, and it's all downhill from here? Or is it a simple retracement, gathering strength to push past $2000? I have no idea. And I make no recommendations.\"",
"title": ""
},
{
"docid": "363043",
"text": "\"A covered call risks the disparity between the purchase price and the potential forced or \"\"called\"\" sale price less the premium received. So buy a stock for $10.00 believing it will drop you or not rise above $14.00 for a given period of days. You sell a call for a $1.00 agreeing to sell your stock for $14.00 and your wrong...the stock rises and at 14.00 or above during the option period the person who paid you the $1.00 premium gets the stock for a net effective price of $15.00. You have a gain of 5$. Your hypothecated loss is unlimited in that the stock could go to $1mil a share. That loss is an opportunity loss you still had a modest profit in actual $. The naked call is a different beast. you get the 1.00 in commission to sell a stock you don't own but must pay for that right. so lets say you net .75 in commission per share after your sell the option. as long as the stock trades below $14.00 during the period of the option you sold your golden. It rises above the strike price you must now buy that stock at market to fill the order when the counter party choses to exercise the option which results in a REAL loss of 100% of the stocks market price less the .75 a share you made. in the scenarios a 1000 shares that for up $30.00 a share over the strike price make you $5,000 in a covered call and lose you $29,250 in a naked call.Naked calls are speculative. Covered calls are strategic.\"",
"title": ""
},
{
"docid": "69395",
"text": "\"Your plan already answers your own question in the best possible way: If you want to be able to make the most possible profit from a large downward move in a stock (in this case, a stock that tracks gold), with a limited, defined risk if there is an upward move, the optimal strategy is to buy a put option. There are a few Exchange Traded Funds (ETFs) that track the price of gold. think of them as stocks that behave like gold, essentially. Two good examples that have options are GLD and IAU. (When you talk about gold, you'll hear a lot about futures. Forget them, for now. They do the same essential thing for your purposes, but introduce more complexity than you need.) The way to profit from a downward move without protection against an upward move is by shorting the stock. Shorting stock is like the opposite of buying it. You make the amount of money the stock goes down by, or lose the amount it goes up by. But, since stocks can go up by an infinite amount, your possible loss is unlimited. If you want to profit on a large downward move without an unlimited loss if you're wrong and it goes up, you need something that makes money as the stock drops, but can only lose so much if it goes up. (If you want to be guaranteed to lose nothing, your best investment option is buying US Treasuries, and you're technically still exposed to the risk that US defaults on its debt, although if you're a US resident, you'll likely have bigger problems than your portfolio in that situation.) Buying a put option has the exact asymmetrical exposure you want. You pay a limited premium to buy it, and at expiration you essentially make the full amount that the stock has declined below the strike price, less what you paid for the option. That last part is important - because you pay a premium for the option, if it's down just a little, you might still lose some or all of what you paid for it, which is what you give up in exchange for it limiting your maximum loss. But wait, you might say. When I buy an option, I can lose all of my money, cant I? Yes, you can. Here's the key to understanding the way options limit risk as compared to the corresponding way to get \"\"normal\"\" exposure through getting long, or in your case, short, the stock: If you use the number of options that represent the number of shares you would have bought, you will have much, much less total money at risk. If you spend the same \"\"bag 'o cash\"\" on options as you would have spent on stock, you will have exposure to way more shares, and have the same amount of money at risk as if you bought the stock, but will be much more likely to lose it. The first way limits the total money at risk for a similar level of exposure; the second way gets you exposure to a much larger amount of the stock for the same money, increasing your risk. So the best answer to your described need is already in the question: Buy a put. I'd probably look at GLD to buy it on, simply because it's generally a little more liquid than IAU. And if you're new to options, consider the following: \"\"Paper trade\"\" first. Either just keep track of fake buys and sells on a spreadsheet, or use one of the many online services where you can track investments - they don't know or care if they're real or not. Check out www.888options.com. They are an excellent learning resource that isn't trying to sell you anything - their only reason to exist is to promote options education. If you do put on a trade, don't forget that the most frustrating pitfall with buying options is this: You can be basically right, and still lose some or all of what you invest. This happens two ways, so think about them both before you trade: If the stock goes in the direction you think, but not enough to make back your premium, you can still lose. So you need to make sure you know how far down the stock has to be to make back your premium. At expiration, it's simple: You need it to be below the strike price by more than what you paid for the option. With options, timing is everything. If the stock goes down a ton, or even to zero - free gold! - but only after your option expires, you were essentially right, but lose all your money. So, while you don't want to buy an option that's longer than you need, since the premium is higher, if you're not sure if an expiration is long enough out, it isn't - you need the next one. EDIT to address update: (I'm not sure \"\"not long enough\"\" was the problem here, but...) If the question is just how to ensure there is a limited, defined amount you can lose (even if you want the possible loss to be much less than you can potentially make, the put strategy described already does that - if the stock you use is at $100, and you buy a put with a 100 strike for $5, you can make up to $95. (This occurs if the stock goes to zero, meaning you could buy it for nothing, and sell it for $100, netting $95 after the $5 you paid). But you can only lose $5. So the put strategy covers you. If the goal is to have no real risk of loss, there's no way to have any real gain above what's sometimes called the \"\"risk-free-rate\"\". For simplicity's sake, think of that as what you'd get from US treasuries, as mentioned above. If the goal is to make money whether the stock (or gold) goes either up or down, that's possible, but note that you still have (a fairly high) risk of loss, which occurs if it fails to move either up or down by enough. That strategy, in its most common form, is called a straddle, which basically means you buy a call and a put with the same strike price. Using the same $100 example, you could buy the 100-strike calls for $5, and the 100-strike puts for $5. Now you've spent $10 total, and you make money if the stock is up or down by more than $10 at expiration (over 110, or under 90). But if it's between 90 and 100, you lose money, as one of your options will be worthless, and the other is worth less than the $10 total you paid for them both.\"",
"title": ""
},
{
"docid": "232880",
"text": "A long put - you have a small initial cost (the option premium) but profit as the stock goes down. You have no additional risk if the shock rises, even a lot. Short a stock - you gain if the stock drops, but have unlimited risk if it rises, the call mitigates this, by capping that rising stock risk. The profit/loss graph looks similar to the long put when you hold both the short position and the long call. You might consider producing a graph or spreadsheet to compare positions. You can easily sketch put, call, long stock, short stock, and study how combinations of positions can synthetically look like other positions. Often, when a stock has no shares to short, the synthetic short can help you put your stock position in place.",
"title": ""
},
{
"docid": "336541",
"text": "\"There is unlimited risk in taking a naked call option position. The only risk in taking a covered call position is that you will be required to sell your shares for less than the going market price. I don't entirely agree with the accepted answer given here. You would not lose the amount you paid to buy the shares. Naked Call Option Suppose take a naked call option position by selling a call option. Since there is no limit on how high the price of the underlying share can go, you can be forced to either buy back the option at a very high price, or, in the case that the option is exercised, you can be force. to buy the underlying shares at a very high price and then sell them to the option holder at a very low price. For example, suppose you sell an Apple call option with a strike price of $100 at a premium of $2.50, and for this you receive a payment of $250. Now, if the price of Apple skyrockets to, say, $1000, then you would either have to buy back the option for about $90,000 = 100 x ($1000-$100), or, if the holder exercised the option, then you would need to buy 100 Apple shares at the market price of $1000 per share, costing you $100,000, and then sell them to the option holder at the strike price of $100 for $10,000 = 100 x $100. In either case, you would show a loss of $90,000 on the share transaction, which would be slightly offset by a $250 credit for the premium you received selling the call. There is no limit on the potential loss since there is no limit on how high the underlying share price can go. Covered Call Option Consider now the case of a covered call option. Since you hold the underlying shares, any loss you make on the option position would be \"\"covered\"\" by the profit you make on the underlying shares. Again, suppose you own 100 Apple shares and sell a call option with a strike price of $100 at a premium of $2.50 to earn a payment of $250. If the price of Apple skyrockets to $1000, then there are again two possible scenarios. One, you buy back the option at a premium of about $900 costing you $90,000. In order to cover this cost you would then sell your 100 Apple shares at the market price of $1000 per share to realise $100,000 = 100 x $1000. On the other hand, if your option is exercised, then you would deliver your 100 Apple shares to the option holder at the contracted strike price of $100 per share, thus receiving just $10,000 = 100 x $100. The only \"\"loss\"\" is that you have had to sell your shares for much less than the market price.\"",
"title": ""
},
{
"docid": "209359",
"text": "When you short a stock, you can lose an unlimited amount of money if the trade goes against you. If the shorted stock gaps up overnight you can lose more money than you have in your account. The best case is you make 100% if the stock goes to zero. And then you have margin fees on top of that. With long positions, it's the other way around. Your max loss is 100% and your gains are potentially unlimited.",
"title": ""
},
{
"docid": "12542",
"text": "Short selling can be a good strategy to hedge, but you have almost unlimited downside. If a stock price skyrockets, you may be forced to cover your short by the brokerage before you want to or put up more capital. A smarter strategy to hedge, that limits your potential downside is to buy puts if you think the market is going down. Your downside is limited to the total amount that you purchased the put for and no more. Another way to hedge is to SELL calls that are covered because you own the shares the calls refer to. You might do this if you thought your stock was going to go down but you didn't want to sell your shares right now. That way the only downside if the price goes up is you give up your shares at a predetermined price and you miss out on the upside, but your downside is now diminished by the premium you were paid for the option. (You'd still lose money if the shares went down since you still own them, but you got paid the option premium so that helps offset that).",
"title": ""
},
{
"docid": "240215",
"text": "\"The process of borrowing shares and selling them is called shorting a stock, or \"\"going short.\"\" When you use money to buy shares, it is called \"\"going long.\"\" In general, your strategy of going long and short in the same stock in the same amounts does not gain you anything. Let's look at your two scenarios to see why. When you start, LOOT is trading at $20 per share. You purchased 100 shares for $2000, and you borrowed and sold 100 shares for $2000. You are both long and short in the stock for $2000. At this point, you have invested $2000, and you got your $2000 back from the short proceeds. You own and owe 100 shares. Under scenario A, the price goes up to $30 per share. Your long shares have gone up in value by $1000. However, you have lost $1000 on your short shares. Your short is called, and you return your 100 shares, and have to pay interest. Under this scenario, after it is all done, you have lost whatever the interest charges are. Under scenario B, the prices goes down to $10 per share. Your long shares have lost $1000 in value. However, your short has gained $1000 in value, because you can buy the 100 shares for only $1000 and return them, and you are left with the $1000 out of the $2000 you got when you first sold the shorted shares. However, because your long shares have lost $1000, you still haven't gained anything. Here again, you have lost whatever the interest charges are. As explained in the Traders Exclusive article that @RonJohn posted in the comments, there are investors that go long and short on the same stock at the same time. However, this might be done if the investor believes that the stock will go down in a short-term time frame, but up in the long-term time frame. The investor might buy and hold for the long term, but go short for a brief time while holding the long position. However, that is not what you are suggesting. Your proposal makes no prediction on what the stock might do in different periods of time. You are only attempting to hedge your bets. And it doesn't work. A long position and a short position are opposites to each other, and no matter which way the stock moves, you'll lose the same amount with one position that you have gained in the other position. And you'll be out the interest charges from the borrowed shares every time. With your comment, you have stated that your scenario is that you believe that the stock will go up long term, but you also believe that the stock is at a short-term peak and will drop in the near future. This, however, doesn't really change things much. Let's look again at your possible scenarios. You believe that the stock is a long-term buy, but for some reason you are guessing that the stock will drop in the short-term. Under scenario A, you were incorrect about your short-term guess. And, although you might have been correct about the long-term prospects, you have missed this gain. You are out the interest charges, and if you still think the stock is headed up over the long term, you'll need to buy back in at a higher price. Under scenario B, it turns out that you were correct about the short-term drop. You pocket some cash, but there is no guarantee that the stock will rise anytime soon. Your investment has lost value, and the gain that you made with your short is still tied up in stocks that are currently down. Your strategy does prevent the possibility of the unlimited loss inherent in the short. However, it also prevents the possibility of the unlimited gain inherent in the long position. And this is a shame, since you fundamentally believe that the stock is undervalued and is headed up. You are sabotaging your long-term gains for a chance at a small short-term gain.\"",
"title": ""
},
{
"docid": "171819",
"text": "\"There some specific circumstances when you would have a long-term gain. Option 1: If you meet all of these conditions: Then you've got a long-term gain on the stock. The premium on the option gets rolled into the capital gain on the stock and is not taxed separately. From the IRS: If a call you write is exercised and you sell the underlying stock, increase your amount realized on the sale of the stock by the amount you received for the call when figuring your gain or loss. The gain or loss is long term or short term depending on your holding period of the stock. https://www.irs.gov/publications/p550/ch04.html#en_US_2015_publink100010630 Option 2: If you didn't hold the underlying and the exercise of the call that you wrote resulted in a short position, you might also be able to get to a long-term gain by buying the underlying while keeping your short position open and then \"\"crossing\"\" them to close both positions after one year. (In other words, don't \"\"buy to cover\"\" just \"\"buy\"\" so that your account shows both a long and a short position in the same security. Your broker probably allows this, but if not you, could buy in a different account than the one with the short position.) That would get you to this rule: As a general rule, you determine whether you have short-term or long-term capital gain or loss on a short sale by the amount of time you actually hold the property eventually delivered to the lender to close the short sale. https://www.irs.gov/publications/p550/ch04.html#en_US_2015_publink100010586 Option 1 is probably reasonably common. Option 2, I would guess, is uncommon and likely not worthwhile. I do not think that the wash sale rules can help string along options from expiration to expiration though. Option 1 has some elements of what you wrote in italics (I find that paragraph a bit confusing), but the wash sale does not help you out.\"",
"title": ""
},
{
"docid": "521644",
"text": "Buying the underlying asset will not completely hedge you, only what lies above 155 dollars (strike + price of option) - you still have the risk of losing everything but 5. You have a maximum earnings-potential of 55 dollars (strike of 150 - investment of 100 + option of 5) but you have a risk of losing 95$ (investment of 100 - option of 5). Say chance of winning everything or losing everything is 50-50, your expected outcome is 0.5 x -95 + 0.5 x 55 = -20$. Is this a great investment? Sure you don't know your odds - otherwise it would be a sure thing. You shouldn't sell the call option if you do not expect prices to go up - but in that case - why not just buy the underlying alone? Speculating in options is a dangerous game with infinite earnings-potential but also infinite loss potential. (Consider selling a call option and not buying the underlying and the price goes from 100 to 1.000.000.000).",
"title": ""
},
{
"docid": "22916",
"text": "On expiry, with the underlying share price at $46, we have : You ask : How come they substract 600-100. Why ? Because you have sold the $45 call to open you position, you must now buy it back to close your position. This will cost you $100, so you are debited for $100 and this debit is being represented as a negative (subtracted); i.e., -$100 Because you have purchased the $40 call to open your position, you must now sell it to close your position. Upon selling this option you will receive $600, so you are credited with $600 and this credit is represented as a positive (added) ; i.e., +$600. Therefore, upon settlement, closing your position will get you $600-$100 = $500. This is the first point you are questioning. (However, you should also note that this is the value of the spread at settlement and it does not include the costs of opening the spread position, which are given as $200, so you net profit is $500-$200 = $300.) You then comment : I know I am selling 45 Call that means : As a writer: I want stock price to go down or stay at strike. As a buyer: I want stock price to go up. Here, note that for every penny that the underlying share price rises above $45, the money you will pay to buy back your short $45 call option will be offset by the money you will receive by selling the long $40 call option. Your $40 call option is covering the losses on your short $45 call option. No matter how high the underlying price settles above $45, you will receive the same $500 net credit on settlement. For example, if the underlying price settles at $50, then you will receive a credit of $1000 for selling your $40 call, but you will incur a debit of $500 against for buying back your short $45 call. The net being $500 = $1000-$500. This point is made in response to your comments posted under Dr. Jones answer.",
"title": ""
},
{
"docid": "507828",
"text": "\"I'm adding to @Dilip's basic answer, to cover the additional points in your question. I'll assume you are referring to publicly traded stock options, such as those found on the CBOE, and not an option contract entered into privately between two specific counterparties (e.g. as in an employer stock option plan). Since you are not obligated to exercise a call option you purchased on the market, you don't need to maintain funds on account for possible exercising. You could instead let the option expire, or resell the option, neither of which requires funds available for purchase of the underlying shares. However, should you actually choose to exercise the call option (and usually this is done close to expiration, if at all), you will be required to fund your account much like if you bought the underlying shares in the first place. Call your broker to determine the exact rules and timing for when they need the money for a call-option exercise. And to expand on the idea of \"\"cancelling\"\" an option you purchased: No, you cannot \"\"cancel\"\" an option contract, per se. But, you are permitted to sell the call option to somebody else willing to buy, via the market. When you sell your call option, you'll either make or lose money on the sale – depending on the price of the underlying shares at the time (are they in- or out- of the money?), volatility in the market, and remaining time value. Once you sell, you're back to \"\"no position\"\". That's not the same as \"\"cancelled\"\", but you are out of the trade, whether at profit or loss. Furthermore, the option writer (i.e. the seller who \"\"sold to open\"\" a position, in writing the call in the first place) is also not permitted to cancel the option he wrote. However, the option writer is permitted to close out the original short position by simply buying back a matching call option on the market. Again, this would occur at either profit or loss based on market prices at the time. This second kind of buy order – i.e. made by someone who initially wrote a call option – is called a \"\"buy to close\"\", meaning the purchase of an offsetting position. (The other kind of buy is the \"\"buy to open\"\".) Then, consider: Since an option buyer is free to re-sell the option purchased, and since an option writer (who \"\"sold to open\"\" the new contract) is also free to buy back an offsetting option, a process known as clearing is required to match remaining buyers exercising the call options held with the remaining option writers having open short positions for the contract. For CBOE options, this clearing is performed by the Options Clearing Corporation. Here's how it works (see here): What is the OCC? The Options Clearing Corporation is the sole issuer of all securities options listed at the CBOE, four other U.S. stock exchanges and the National Association of Securities Dealers, Inc. (NASD), and is the entity through which all CBOE option transactions are ultimately cleared. As the issuer of all options, OCC essentially takes the opposite side of every option traded. Because OCC basically becomes the buyer for every seller and the seller for every buyer, it allows options traders to buy and sell in a secondary market without having to find the original opposite party. [...] [emphasis above is mine] When a call option writer must deliver shares to a call option buyer exercising a call, it's called assignment. (I have been assigned before, and it isn't pleasant to see a position called away that otherwise would have been very profitable if the call weren't written in the first place!) Also, re: \"\"I know my counter party cannot sell his shares\"\" ... that's not strictly true. You are thinking of a covered call. But, an option writer doesn't necessarily need to own the underlying shares. Look up Naked call (Wikipedia). Naked calls aren't frequently undertaken because a naked call \"\"is one of the riskiest options strategies because it carries unlimited risk\"\". The average individual trader isn't usually permitted by their broker to enter such an order, but there are market participants who can do such a trade. Finally, you can learn more about options at The Options Industry Council (OIC).\"",
"title": ""
},
{
"docid": "388754",
"text": "\"The question you are asking concerns the exercise of a short option position. The other replies do not appear to address this situation. Suppose that Apple is trading at $96 and you sell a put option with a strike price of $95 for some future delivery date - say August 2016. The option contract is for 100 shares and you sell the contract for a premium of $3.20. When you sell the option your account will be credited with the premium and debited with the broker commission. The premium you receive will be $320 = 100 x $3.20. The commission you pay will depend on you broker. Now suppose that the price of Apple drops to $90 and your option is exercised, either on expiry or prior to expiry. Then you would be obliged to take delivery of 100 Apple shares at the contracted option strike price of $95 costing you $9,500 plus broker commission. If you immediately sell the Apple shares you have purchased under your contract obligations, then assuming you sell the shares at the current market price of $90 you would realise a loss of $500 ( = 100x($95-$90) )plus commission. Since you received a premium of $320 when you sold the put option, your net loss would be $500-$320 = $180 plus any commissions paid to your broker. Now let's look at the case of selling a call option. Again assume that the price of Apple is $96 and you sell a call option for 100 shares with a strike price of $97 for a premium of $3.60. The premium you receive would be $360 = 100 x $3.60. You would also be debited for commission by your broker. Now suppose that the price of Apple shares rises to $101 and your option is exercised. Then you would be obliged to deliver 100 Apple shares to the party exercising the option at the contracted strike price of $97. If you did not own the shares to effect delivery, then you would need to purchase those shares in the market at the current market price of $101, and then sell them to the party exercising the option at the strike price of $97. This would realise an immediate loss of $400 = 100 x ($101-$97) plus any commission payable. If you did own the shares, then you would simply deliver them and possibly pay some commission or a delivery fee to your broker. Since you received $360 when you sold the option, your net loss would be $40 = $400-$360 plus any commission and fees payable to the broker. It is important to understand that in addition to these accounting items, short option positions carry with them a \"\"margin\"\" requirement. You will need to maintain a margin deposit to show \"\"good faith\"\" so long as the short option position is open. If the option you have sold moves against you, then you will be called upon to put up extra margin to cover any potential losses.\"",
"title": ""
},
{
"docid": "578022",
"text": "\"You owe no tax on the option transaction in 2015 in this case. How you ultimately get taxed depends on how you dispose of the position. If it expires, then you will have a short-term capital gain on the option position at expiration. If it is exercised, then the option is \"\"gone\"\" for tax purposes and your basis in the underlying is adjusted. From IRS Publication 550: If a call you write is exercised and you sell the underlying stock, increase your amount realized on the sale of the stock by the amount you received for the call when figuring your gain or loss. The gain or loss is long term or short term depending on your holding period of the stock. In your case, this will be a long-term capital gain. For completeness, if you buy to cover the option back from the market before expiration or exercise, then it is also a short-term capital gain. Also, keep in mind that this all assumes that this covered call is \"\"qualified\"\" so that it does not count as a straddle. You can find more about that in Pub 550. https://www.irs.gov/publications/p550/ch04.html#en_US_2014_publink100010630 All of this is for US tax purposes.\"",
"title": ""
},
{
"docid": "557356",
"text": "\"There are two reasons why most options aren't exercised. The first is obvious, and the second, less so. The obvious: An option that's practically worthless doesn't get exercised. Options that reach expiry and remain unexercised are almost always worthless bets that simply didn't pay off. This includes calls with strikes above the current underlying price, and puts with strikes below it. A heck of a lot of options. If an option with value was somehow left to expire, it was probably a mistake, or else the transaction costs outweighed the value remaining; not quite worthless, but not \"\"worth it\"\" either. The less obvious: An option with value can be cancelled any time before expiration. A trader that buys an option may at some point show a gain sooner than anticipated, or a loss in excess of his tolerance. If a gain, he may want to sell before expiry to realize the gain sooner. Similarly, if a loss, he may want to take the loss sooner. In both cases, his capital is freed up and he can take another position. And — this is the key part — the other end matched up with that option sale is often a buyer that had created (written) exactly such an option contract in the first place – the option writer – and who is looking to get out of his position. Option writers are the traders responsible, in the first place, for creating options and increasing the \"\"open interest.\"\" Anybody with the right kind and level of options trading account can do this. A trader that writes an option does so by instructing his broker to \"\"sell to open\"\" a new instance of the option. The trader then has a short position (negative quantity) in that option, and all the while may be subject to the obligations that match the option's exercise rights. The only way for the option writer to get out of that short position and its obligations are these: Not by choice: To get assigned. That is to say: a buyer exercised the option. The writer has to fulfill his obligation by delivering the underlying (if a call) to the option holder, or buying the underlying (if a put) from the option holder. Not by choice: The option expires worthless. This is the ideal scenario for a writer because 100% of the premium received (less transaction costs) is profit. By choice: The writer is free to buy back exactly the same kind of option before expiry using a \"\"buy to close\"\" order with their broker. Once the option has been purchased with a \"\"buy to close\"\", it eliminates the short position and obligation. The option is cancelled. The open interest declines. Options thus cancelled just don't live long enough to either expire or be exercised.\"",
"title": ""
},
{
"docid": "268802",
"text": "Without commenting on your view of the TV market: Let's have a look at the main ways to get negative exposure: 1.Short the stocks Pros: Relatively Easy Cons: Interest rate, costs of shorting, linear bet 2.Options a. Write Calls b. Buy puts Pros: Convexity, leveraged, relatively cheap Cons: Zero Sum bet that expires with time, theta 3.Short Stock, Buy Puts, Write Calls Short X Units of each stock, Write calls on them , use call premiums to finance puts. Pros: 3x the power!, high kickout Cons: Unlimited pain",
"title": ""
},
{
"docid": "393418",
"text": "By buying the call option, you are getting the benefit of purchasing the underlying shares (that is, if the shares go up in value, you make money), but transferring the risk of the shares reducing in value. This is more apparent when you are using the option to offset an explicit risk that you hold. For example, if you have a short position, you are at unlimited risk of the position going up in value. You could decide you only want to take the risk that it might rise to $X. In that case, you could buy a call option with $X strike price. Then you have transferred the risk that the position goes over $X to the counterpart, since, even if the shares are trading at $X+$Y you can close out the short position by purchasing the shares at $X, while the option counterpart will lose $Y.",
"title": ""
},
{
"docid": "520098",
"text": "\"A derivative contract can be an option, and you can take a short (sell) position , much the same way you would in a stock. When BUYING options you risk only the money you put in. However when selling naked(you don't have the securities or cash to cover all potential losses) options, you are borrowing. Brokers force you to maintain a required amount of cash called, a maintenance requirement. When selling naked calls - theoretically you are able to lose an INFINITE amount of money, so in order to sell this type of options you have to maintain a certain level of cash in your account. If you fail to maintain this level you will enter into whats often referred to as a \"\"margin-call\"\". And yes they will call your phone and tell you :). Your broker has the right to liquidate your positions in order to meet requirements. PS: From experience my broker has never liquidated any of my holdings, but then again I've never been in a margin call for longer then a few days and never with a severe amount. The margin requirement for investors is regulated and brokers follow these regulations.\"",
"title": ""
},
{
"docid": "314478",
"text": "\"And what exactly do I profit from the short? I understand it is the difference in the value of the stock. So if my initial investment was $4000 (200 * $20) and I bought it at $3800 (200 * $19) I profit from the difference, which is $200. Do I also receive back the extra $2000 I gave the bank to perform the trade? Either this is extremely poorly worded or you misunderstand the mechanics of a short position. When you open a short position, your are expecting that the stock will decline from here. In a short position you are borrowing shares you don't own and selling them. If the price goes down you get to buy the same shares back for less money and return them to the person you borrowed from. Your profit is the delta between the original sell price and the new lower buy price (less commissions and fees/interest). Opening and closing a short position is two trades, a sell then a buy. Just like a long trade there is no maximum holding period. If you place your order to sell (short) 200 shares at $19, your initial investment is $3,800. In order to open your $3,800 short position your broker may require your account to have at least $5,700 (according to the 1.5 ratio in your question). It's not advisable to open a short position this close to the ratio requirement. Most brokers require a buffer in your account in case the stock goes up, because in a short trade if the stock goes up you're losing money. If the stock goes up such that you've exhausted your buffer you'll receive what's known as a \"\"margin call\"\" where your broker either requires you to wire in more money or sell part or all of your position at a loss to avoid further losses. And remember, you may be charged interest on the value of the shares you're borrowing. When you hold a position long your maximum loss is the money you put in; a position can only fall to zero (though you may owe interest or other fees if you're trading on margin). When you hold a position short your maximum loss is unlimited; there's no limit to how high the value of something can go. There are less risky ways to make short trades by using put options, but you should ensure that you have a firm grasp on what's happening before you use real money. The timing of the trades and execution of the trades is no different than when you take a plain vanilla long position. You place your order, either market or limit or whatever, and it executes when your trade criteria occurs.\"",
"title": ""
},
{
"docid": "242663",
"text": "\"Some thoughts on your questions in order, Duration: You might want to look at the longest-dated option (often a \"\"LEAP\"\"), for a couple reasons. One is that transaction costs (spread plus commission, especially spread) are killer on options, so a longer option means fewer transactions, since you don't have to keep rolling the option. Two is that any fundamentals-based views on stocks might tend to require 3-5 years to (relatively) reliably work out, so if you're a fundamental investor, a 3-6 month option isn't great. Over 3-6 months, momentum, short-term news, short squeezes, etc. can often dominate fundamentals in determining the price. One exception is if you just want to hedge a short-term event, such as a pending announcement on drug approval or something, and then you would buy the shortest option that still expires after the event; but options are usually super-expensive when they span an event like this. Strike: Strike price on a long option can be thought of as a tradeoff between the max loss and minimizing \"\"insurance costs.\"\" That is, if you buy a deeply in-the-money put or call, the time value will be minimal and thus you aren't paying so much for \"\"insurance,\"\" but you may have 1/3 or 1/2 of the value of the underlying tied up in the option and subject to loss. If you buy a put or call \"\"at the money,\"\" then you might have only say 10% of the value of the underlying tied up in the option and subject to loss, but almost the whole 10% may be time value (insurance cost), so you are losing 10% if the underlying stock price stays flat. I think of the deep in-the-money options as similar to buying stocks on margin (but the \"\"implied\"\" interest costs may be less than consumer margin borrowing rates, and for long options you can't get a margin call). The at-the-money options are more like buying insurance, and it's expensive. The commissions and spreads add significant cost, on top of the natural time value cost of the option. The annual costs would generally exceed the long-run average return on a diversified stock fund, which is daunting. Undervalued/overvalued options, pt. 1: First thing is to be sure the options prices on a given underlying make sense at all; there are things that \"\"should\"\" hold, for example a synthetic long or short should match up to an actual long or short. These kinds of rules can break, for example on LinkedIn (LNKD) after its IPO, when shorting was not permitted, the synthetic long was quite a bit cheaper than a real long. Usually though this happens because the arbitrage is not practical. For example on LNKD, the shares to short weren't really available, so people doing synthetic shorts with options were driving up the price of the synthetic short and down the price of the synthetic long. If you did actually want to be long the stock, then the synthetic long was a great deal. However, a riskless arbitrage (buy synthetic long, short the stock) was not possible, and that's why the prices were messed up. Another basic relationship that should hold is put-call parity: http://en.wikipedia.org/wiki/Put%E2%80%93call_parity Undervalued/overvalued options, pt. 2: Assuming the relationship to the underlying is sane (synthetic positions equivalent to actual positions) then the valuation of the option could focus on volatility. That is, the time value of the option implies the stock will move a certain amount. If the time value is high and you think the stock won't move much, you might short the option, while if the time value is low and you think the stock will move a lot, you might buy the option. You can get implied volatility from your broker perhaps, or Morningstar.com for example has a bunch of data on option prices and the implied components of the price model. I don't know how useful this really is though. The spreads on options are so wide that making money on predicting volatility better than the market is pretty darn hard. That is, the spread probably exceeds the amount of the mispricing. The price of the underlying is more important to the value of an option than the assumed volatility. How many contracts: Each contract is 100 shares, so you just match that up. If you want to hedge 100 shares, buy one contract. To get the notional value of the underlying multiply by 100. So say you buy a call for $30, and the stock is trading at $100, then you have a call on 100 shares which are currently priced at $10,000 and the option will cost $30*100=3,000. You are leveraged about 3 to 1. (This points to an issue with options for individual investors, which is that one contract is a pretty large notional value relative to most portfolios.)\"",
"title": ""
},
{
"docid": "326599",
"text": "Gold's valuation is so stratospheric right now that I wonder if negative numbers (as in, you should short it) are acceptable in the short run. In the long run I'd say the answer is zero. The problem with gold is that its only major fundamental value is for making jewelry and the vast majority is just being hoarded in ways that can only be justified by the Greater Fool Theory. In the long run gold shouldn't return more than inflation because a pile of gold creates no new wealth like the capital that stocks are a claim on and doesn't allow others to create new wealth like money lent via bonds. It's also not an important and increasingly scarce resource for wealth creation in the global economy like oil and other more useful commodities are. I've halfway-thought about taking a short position in gold, though I haven't taken any position, short or long, in gold for the following reasons: Straight up short-selling of a gold ETF is too risky for me, given its potential for unlimited losses. Some other short strategy like an inverse ETF or put options is also risky, though less so, and ties up a lot of capital. While I strongly believe such an investment would be profitable, I think the things that will likely rise when the flight-to-safety is over and gold comes back to Earth (mainly stocks, especially in the more beaten-down sectors of the economy) will be equally profitable with less risk than taking one of these positions in gold.",
"title": ""
},
{
"docid": "142110",
"text": "\"He didn't sell in the \"\"normal\"\" way that most people think of when they hear the term \"\"sell.\"\" He engaged in a (perfectly legitimate) technique known as short selling, in which he borrows shares from his broker and sells them immediately. He's betting that the price of the stock will drop so he can buy them back at a lower price to return the borrowed shares back to his broker. He gets to pocket the difference. He had about $37,000 of cash in his account. Since he borrowed ~8400 shares and sold them immediately at $2/share, he got $16,800 in cash and owed his broker 8400 shares. So, his net purchasing power at the time of the short sale was $37,000 + $16,800 - 4800 shares * $2/share. As the price of the stock changes, his purchasing power will change according to this equation. He's allowed to continue to borrow these 8400 shares as long as his purchasing power remains above 0. That is, the broker requires him to have enough cash on hand to buy back all of his borrowed shares at any given moment. If his purchasing power ever goes negative, he'll be subject to a margin call: the broker will make him either deposit cash into his account or close his positions (sell long positions or buy back short positions) until it's positive again. The stock jumped up to $13.85 the next morning before the market opened (during \"\"before-hours\"\" trading). His purchasing power at that time was $37,000 + $16,800 - 8400 shares * $13.85/share = -$62,540. Since his purchasing power was negative, he was subject to a margin call. By the time he got out, he had to pay $17.50/share to buy back the 8400 shares that he borrowed, making his purchasing power -$101,600. This $101,600 was money that he borrowed from his broker to buy back the shares to fulfill his margin call. His huge loss was from borrowing shares from his broker. Note that his maximum potential loss is unlimited, since there is no limit to how much a stock can grow. Evidently, he failed to grasp the most important concept of short selling, which is that he's borrowing stock from his broker and he's obligated to give that stock back whenever his broker wants, no matter what it costs him to fulfill that obligation.\"",
"title": ""
},
{
"docid": "16747",
"text": "\"The previous answers make valid points regarding the risks, and why you can't reasonably compare trading for profit/loss to a roll of the die. This answer looks at the math instead. Your assumption: I have an equal probability to make a profit or a loss. Is incorrect, for the reasons stated in other answers. However, the answer to your question: Can I also assume that probabilistically speaking, a trader cannot do worst than random? Is \"\"yes\"\". But only because the question is flawed. Consequently it's throwing people in all directions with their answers. But quite simply, in a truly random environment the worst case scenario, no matter how improbable, is that you lose over and over again until you have nothing left. This can happen in sequential rolls of the dice AND in trading securities/bonds/whatever. You could guess wrong for every roll of the die AND all of your stock picks could become worthless. Both outcomes result in $0 (assuming you do not gamble with credit). Tell me, which $0 is \"\"worse\"\"? Given the infinite number of plays that \"\"random\"\" implies, the chance of losing your entire bankroll exists in both scenarios, and that is enough by itself to make neither option \"\"worse\"\" than the other. Of course, the opposite is also true. You could only pick winners, with an unlimited upside potential, but again that could happen with either dice rolls or stock picks. It's just highly improbable. my chances cannot be worse than random and if my trading system has an edge that is greater than the percentage of the transaction that is transaction cost, then I am probabilistically likely to make a profit? Nope. This is where it all falls apart. Just because your chances of losing it all are similarly improbable, does not make you more likely to win with one method or the other. Regression to the mean, when given infinite, truly random outcomes, makes it impossible to \"\"have an edge\"\". Also, \"\"probabilistically\"\" isn't a word, but \"\"probably\"\" is.\"",
"title": ""
},
{
"docid": "147361",
"text": "\"Yes, long calls, and that's a good point. Let's see... if I bought one contract at the Bid price above... $97.13 at expiry of $96.43 option = out of the money =- option price(x100) = $113 loss. $97.13 at expiry of $97.00 option = out of the money =- option price(x100) = $77 loss. $97.13 at expiry of $97.14 option = in the money by 1-cent=$1/contract profit - option price(x100) = $1-$58 = $57 loss The higher strike prices have much lower losses if they expire with the underlying stock at- or near-the-money. So, they carry \"\"gentler\"\" downside potential, and are priced much higher to reflect that \"\"controlled\"\" risk potential. That makes sense. Thanks.\"",
"title": ""
},
{
"docid": "485760",
"text": "\"Do you want to do it pre or post correction? If you're bearish on the market the obvious thing to do is short an index. I would say this is kind of dumb. The main problem is that it may take months or years for the market to crash, and by then it will have gone up so much that even the crash doesn't bring you profit, and you're paying borrowing fees meanwhile as well. You need to watch the portfolio also, when you short sell you'll get a bunch of cash, which you most likely will want to invest, but once you invest it, the market can spike and pummel your short position, resulting in negative remaining cash (since you already spent it). At that point you get a margin call from your broker. If you check your account regularly, not a big deal, but bad things can happen if you treat it as a fire and forget strategy. These days they have inverse funds so you don't have to borrow anything. The fund manager borrows for you. I'd say those are much better. The less cumbersome choice is to simply sell call options on the index or buy puts. These are even cash options, so when you exercise you get/lose money, not shares. You can even arrange them so that your potential loss is capped. (but honestly, same goes for shorts - it's called a stop loss) You could also wait for the correction and buy the dip. Less worrying about shorts and such, but of course the issue is timing the crash. Usually the crashes are very quick, and there are several \"\"pre-crashes\"\" that look like it bottomed out but then it crashes more. So actually very difficult thing to tell. You have to know either exactly when the correction will be, or exactly what the price floor is (and set a limit buy). Hope your crystal ball works! Yet another choice is finding asset classes uncorrelated or even anticorrelated with the broader market. For instance some emerging markets (developing countries), some sectors, individual stocks that are not inflated, bonds, gold and so on can have these characteristics where if S&P goes down they go up. Buying those may be a safer approach since at least you are still holding a fundamentally valuable thing even if your thesis flops, meanwhile shorts and puts and the like are purely speculative.\"",
"title": ""
}
] |
7397
|
When a company reports it earnings, when does the SEC EDGAR system show the report online?
|
[
{
"docid": "594641",
"text": "\"IT appears the company you're talking about did not report as you expected them to, which is not unusual for OTC companies because, as Milo stated, they are not well-managed. That being said, reports on EDGAR are available as soon as they're posted. I'm not aware of any lag between when the company uploads their report and it is available on the EDGAR site. Looking at the profile of the company you're referring to, I'm curious why you'd be so interested in a company with huge negative earnings, a near-zero share price, and an obviously spotty history of reporting its numbers. In order to make any money with this stock, you'd have to buy a huge number of shares, which could be difficult to unload. Further, the fees you're going to pay to make your trades are very likely to outstrip your return, so you'd be upside down on it. This company has pretty negative financials, and in a world of cheap oil, alternative energy (and the companies that deal in it) are out of vogue, so they're not likely to see a turnaround anytime soon. They're spending money on R & D at a rate almost 17 times earnings, and the losses are deepening, while revenues are not improving all that much. These guys are bleeding to death, and there's little prospect of a financial transfusion on the horizon. This is, as they say, a \"\"dog with fleas\"\", so your best bet is to find something else to put your money into. I hope this helps. Good luck!\"",
"title": ""
}
] |
[
{
"docid": "305544",
"text": "\"The SEC requires a certain format when submitting filings, which generally does not line up with how documents are typeset for printing. Rather than typeset the entire document again, it's just sort of accepted that the format in EDGAR will suck. Typesetters actually call the process \"\"EDGARizing.\"\" (I'm not making this up, I used to work in the department at a mutual fund company that put together the financial reports for the funds.) My guess is it's a relic from legacy systems at the SEC that can't handle newer formats like PDF.\"",
"title": ""
},
{
"docid": "391291",
"text": "Yes it is true. The US based companies have to meet the requirements placed on them by the US government. The agency with all these reports is the Security and Exchange Commission. They run the EDGAR system to hold all those required reports The SEC’s EDGAR database provides free public access to corporate information, allowing you to quickly research a company’s financial information and operations by reviewing registration statements, prospectuses and periodic reports filed on Forms 10-K and 10-Q. You also can find information about recent corporate events reported on Form 8-K but that a company does not have to disclose to investors. EDGAR also provides access to comment and response letters relating to disclosure filings made after August 1, 2004, and reviewed by either the Division of Corporation Finance or the Division of Investment Management. On May 22, 2006, the staffs of the Divisions of Corporation Finance and Investment Management began to use the EDGAR system to issue notifications of effectiveness for Securities Act registration statements and post-effective amendments, other than those that become effective automatically by law. These notifications will be posted to the EDGAR system the morning after a filing is determined to be effective. As pointed out by Grade 'Eh' Bacon: Other countries may require different types of information to be reported to the public, in particular, financial statements. To find the financial statements released for a particular company, you can go to the appropriate stock exchange, or often simply the company's corporate website.",
"title": ""
},
{
"docid": "399284",
"text": "Compensation information is available in the annual reports (10-k filings) which are available from the SEC EDGAR system or, generally, the company's website. Additionally, insider transactions are reported to the SEC so you can see when an insider buys or sells stock or exercises options received as compensation. Background: Nowadays board and officers seem to secretly steal money from shareholders through options and other ways. The stock buybacks that people think should boost the earnings per stock is in reality issued back to the management of the company and is a more stealth way to take money from the company compared to take higher salaries. ... How do you know this is happening if you don't know where to go to get the data needed to determine whether or not this is happening? Do you really think company share buybacks involve just the amount of shares to pay an executive? Apple has bought back $117,000,000,000 worth of shares from the fourth quarter 2012 through the second quarter 2016, and paid a pretty substantial amount in dividends over the same period. Do you really think these shares were simply handed to the executives? The huge pension funds and other huge investors would not let this slide for very long if it were even close to being true. Don't come to an unfounded conclusion then seek data to prove your position. Look at and analyze data THEN come to a conclusion.",
"title": ""
},
{
"docid": "56292",
"text": "\"Edgar Online has this information for companies under SEC regulations and they are reported in \"\"Form 4\"\" so that should help guide your search\"",
"title": ""
},
{
"docid": "92593",
"text": "Edgar Online is the SEC's reporting repository where public companies post their forms, these forms contain financial data Stock screeners allow you to compare many companies based on many financial metrics. Many sites have them, Google Finance has one with a decent amount of utility",
"title": ""
},
{
"docid": "125981",
"text": "You can find out the general types of investments by reading the public corporation 10-Q report that is filed with the SEC it can be accessed via the EDGAR system. It will not tell you what securities they have, but it does identify the short term and long term investments categories and their value.",
"title": ""
},
{
"docid": "441155",
"text": "Schedule 13D (or the abbreviated version, schedule 13G) would be the most likely place to find this info. When a person or group of persons acquires beneficial ownership of more than 5% of a voting class of a company’s equity securities registered under Section 12 of the Securities Exchange Act of 1934, they are required to file a Schedule 13D with the SEC. Schedule 13D reports the acquisition and other information within ten days after the purchase. Any material changes in the facts contained in the schedule require a prompt amendment. You can find the Schedules 13D for most publicly traded companies in the SEC’s EDGAR database. A 1% change in the amount of ownership is considered material.",
"title": ""
},
{
"docid": "502560",
"text": "\"Crowdfunding can be a legitimate means of funding very small startups. It is an innovative, but obviously risky, method of raising small amounts of money. As such it is now regulated by the SEC under \"\"Regulation Crowdfunding\"\" They have published guides for these types of business startups to help them with required disclosures and reporting requirements: https://www.sec.gov/info/smallbus/secg/rccomplianceguide-051316.htm Here's the introduction to the relevant regulatory authority of the SEC: Under the Securities Act of 1933, the offer and sale of securities must be registered unless an exemption from registration is available. Title III of the Jumpstart Our Business Startups (JOBS) Act of 2012 added Securities Act Section 4(a)(6) that provides an exemption from registration for certain crowdfunding transactions.[2] In 2015, the Commission adopted Regulation Crowdfunding to implement the requirements of Title III.[3] Under the rules, eligible companies will be allowed to raise capital using Regulation Crowdfunding starting May 16, 2016. It is obviously a new form of investment but you should be able to get historical data on the SEC's real time Edgar reporting system once there is some history. This is a search for all Form C's filed as of 12/2/16\"",
"title": ""
},
{
"docid": "347523",
"text": "according to the SEC: Shareholder Reports A mutual fund and a closed-end fund respectively must provide shareholders with annual and semi-annual reports 60 days after the end of the fund’s fiscal year and 60 days after the fund’s fiscal mid-year. These reports contain updated financial information, a list of the fund’s portfolio securities, and other information. The information in the shareholder reports will be current as of the date of the particular report (that is, the last day of the fund’s fiscal year for the annual report, and the last day of the fund’s fiscal mid-year for the semi-annual report). Other Reports A mutual fund and a closed-end fund must file a Form N-Q each quarter and a Form N-PX each year on the SEC’s EDGAR database, although funds are not required to mail these reports to shareholders. Funds disclose portfolio holdings on Form N-Q. Form N-PX identifies specific proposals on which the fund has voted portfolio securities over the past year and discloses how the fund voted on each. This disclosure enables fund shareholders to monitor their funds’ involvement in the governance activities of portfolio companies. which means that sixty days after the end of each quarter they will tell you what they owned 60 days ago. This makes sense; why would they want to tell the world what companies they are buying and selling.",
"title": ""
},
{
"docid": "545558",
"text": "There could be an impact on Facebook because just before the IPO, Morgan Stanley apparently sent information to selected clients that their analysts had just lowered their valuation of the company. There were also reports yesterday that the lowered valuation came about because Facebook sent some revised preliminary estimates of second quarter earnings (showing lower than expected earnings) to Morgan Stanley, and least one talking head said that Facebook might also face charges depending on what the cover letters and the e-mails back and forth between Facebook and Morgan Stanley said. Investigations have already been opened. Yes, a company wants to sell the stock being offered at the IPO at the highest price possible, but if it misled the public when offering the stock for sale (through its underwriters), it can also be liable, possibly even criminally liable. Material added in Edit: In fact, a lawsuit has already been filed in the US District Court in Manhattan in this matter. Whether the SEC ever does anything about the matter remains to be seen.",
"title": ""
},
{
"docid": "63848",
"text": "The only way for a mutual fund to default is if it inflated the NAV. I.e.: it reports that its investments worth more than they really are. Then, in case of a run on the fund, it may end up defaulting since it won't have the money to redeem shares at the NAV it published. When does it happen? When the fund is mismanaged or is a scam. This happened, for example, to the fund Madoff was managing. This is generally a sign of a Ponzi scheme or embezzlement. How can you ensure the funds you invest in are not affected by this? You'll have to read the fund reports, check the independent auditors' reports and check for clues. Generally, this is the job of the SEC - that's what they do as regulators. But for smaller funds, and private (i.e.: not public) investment companies, SEC may not be posing too much regulations.",
"title": ""
},
{
"docid": "31516",
"text": "You can take a look at EDGAR (Electronic Data Gathering, Analysis, and Retrieval), a big database run by the SEC where all companies, foreign and domestic, are required to file registration statements, periodic reports, and other forms electronically.",
"title": ""
},
{
"docid": "553066",
"text": "SEC forms are required when declaring insider activity. An insider is defined by the SEC to be a person or entity which (i) beneficially owns 10% or more of the outstanding shares of the company, (ii) is an officer or director of the company, or (iii), in the case of insider trading, does so based on knowledge which is not otherwise publically available at the time. At any rate, the person or entity trading the stock is required to file certain forms. Form 3 is filed when a person first transitions into the status of an insider (by becoming an officer, director, or beneficial owner of a certain percentage of stock). Form 4 is filed when an existing insider trades stock under the company's symbol. Form 5 is filed when certain insider trades of small value are reported later than usual. *More information can be found at the SEC's website. Another possibility is that a large number of options or derivatives were exercised by an officer, director, or lending institution. In the cases of officers or directors, this would need to be declared with an SEC form 4. For an institution exercising warrants obtained as a result of a lending agreement, either form 3 or 4 would need to be filed. In addition to the above possibilities, username passing through pointed out a very likely scenario in his answer, as well.",
"title": ""
},
{
"docid": "27067",
"text": "My company has a dashboard that basically does this. We select industries / companies we want to be notified of and we get an email in outlook when a new analyst note, research report, or SEC filing is posted on that industry or company.",
"title": ""
},
{
"docid": "161411",
"text": "\"For US equities, Edgar Online is where companies post their government filings to the SEC. On Google Finance, you would look at the \"\"SEC filings\"\" link on the page, and then find their 10K and 10Q documents, where that information is listed and already calculated. Many companies also have these same documents posted on their Investor Relations web pages.\"",
"title": ""
},
{
"docid": "11263",
"text": "The actual financial statements should always be referenced first before opening or closing a position. For US companies, they are freely available on EDGAR. Annual reports are called 10-Ks, and quarterly reports are called 10-Qs. YHOO and GOOG do a great job of posting financials that are quickly available, but money.msn has the best. These should be starting point, quick references. As you can see, they may all have the same strange accounting. Sometimes, it's difficult to find the information one seeks in the consolidated financial statements as in this case, so searching through the filing is necessary. The notes can be helpful, but Ctrl-F seems to do everything I need when I want something in a report. In AAPL's case, the Interest expense can be found in Note 3.",
"title": ""
},
{
"docid": "327814",
"text": "First utilize a security screener to identify the security profiles you are looking to identify for identifying your target securities for shorting. Most online brokers have stock screeners that you can utilize. At this point you may want to look at your target list of securities to find out those that are eligible for shorting. The SHO thresold list is also a good place to look for securities that are hard to borrow to eliminate potential target securities. http://regsho.finra.org/regsho-Index.html Also your broker can let you know the stocks that are available for borrowing. You can then take your target securities and then you can look at the corporate filings on the SEC's Edgar site to look for the key words you are looking for. I would suggest that you utilize XBRL so you can electronically run your key word searched in an automated manner. I would further suggest that you can run the key word XBRL daily for issuer filings of your target list of securities. Additional word searches you may want to consider are those that could indicate a dilution of the companies stock such as the issuance of convertible debt. Also the below link detailing real short interest may be helpful. Clearing firms are required to report short interest every two weeks. http://www.nasdaq.com/quotes/short-interest.aspx",
"title": ""
},
{
"docid": "251303",
"text": "You can avoid companies that might go bankrupt by not buying the stock of companies with debt. Every quarter, a public company must file financials with the EDGAR system called a 10-Q. This filing includes unaudited financial statements and provides a continuing view of the company's financial position during the year. Any debt the company has acquired will appear on this filing and their annual report. If servicing the debt is costing the company a substantial fraction of their income, then the company is a bankruptcy risk.",
"title": ""
},
{
"docid": "174714",
"text": "\"When you pay the flight, hotel, conference attendance fees of $100: When you repay the credit card debt of $100: When you receive the gross salary of $5000: Your final balance sheet will show: Your final income statement will show: Under this method, your \"\"Salary\"\" account will show the salary net of business expense. The drawback is that the $4900 does not agree with your official documentation. For tax reporting purposes, you report $5000 to the tax agency, and if possible, report the $100 as Unreimbursed Employee Expenses (you weren't officially reimbursed). For more details see IRS Publication 529.\"",
"title": ""
},
{
"docid": "146076",
"text": "\"Publicly traded companies files 10-Ks with the SEC, searchable on the EDGAR system. If you want basic financial statement info then look for 10-Ks that are marked \"\"Interactive Data\"\", as for those the SEC has broken everything out by statement into standard formats. You could also use marketwatch which puts everything in financial statements into the same or as similar of categories as it can to make it easier to compare companies.\"",
"title": ""
},
{
"docid": "191677",
"text": "10-Q is the quarterly report, and accordingly is filed quarterly. Similarly, 10-K is the annual report. 8-K is a general form for notification of material events. It is filed every time a material event is required to be reported to the shareholders. It may accompany the periodical reports, but doesn't have to. It can be filed on its own. If you're only interested in the financial statements, then you should be looking for the 10K/10Q forms. SEC will tell you when the forms were filed (dates), but it won't tell you what's more material and what's less. So you can plot a stock price graph on these dates, and see what was deemed more material by the investors based on the price fluctuations, but be prepared to find fluctuations that have no correlation to filings - because the market as a whole can drag the stock up or down. Also, some events may not be required to be reported to SEC, but may be deemed material by the investors. For example, a Cupertino town hall meeting discussing the zoning for the new AAPL HQ building may be deemed material by the investors, based on the sentiments, even if no decision was made to be reported to SEC.",
"title": ""
},
{
"docid": "246586",
"text": "Brokerage firms are required to report the number of shares being shorted. This information is reported to the exchange (NYSE of NASDAQ) and is made public. Most financial sites indicate the number of shares being shorted for a particular stock. The image below from Yahoo finance shows 3.29 million shares of CMG were being shorted at the close of 9-28-2012. This is over 12% of the total outstanding shares of CMG. For naked short selling additional information is tracked. If the brokerage is unable to borrow shares to deliver before the settlement date of a short sale then the transaction is recorded as fails-to-deliver. No money or shares are exchanged since the brokerage is unable to deliver the shares that were agreed upon. A large amount of fails-to-deliver transactions for a stock usually indicates an excessive amount of naked shorting. When investors and brokerage firms start to aggressively short a stock they will do so without having borrowed the shares to sell. This will result in a large amount of naked short selling. When there are a large number of naked short sellers not all the sellers will be able to borrow the necessary shares before the settlement date and many fails-to-deliver transactions will be recorded. The SEC records the number of fails-to-deliver transactions. The table below summarizes the fails-to-deliver transactions from 1-1-2012 through 9-14-2012 (data obtained from here). The “Ext Amount” column shows the total dollar value of the transactions that failed ( i.e. Fail Qty * Share price ). The “Volume” column is the total number of shares traded in the same time period. The “% Volume” shows the percentage of shares that failed to deliver as a percentage of the total market volume. The table orders the data in descending order by the quantity of shares that were not delivered. Most of the companies at the top of the list no longer exist. For many of these companies, the quantity of shares that failed to deliver where many multiples of the number of shares traded during the same time period. This indicates massive naked short selling as many brokerages where unable to find shares to borrow before the settlement date. More information here.",
"title": ""
},
{
"docid": "45718",
"text": "\"I use online banking as much as possible and I think it may help you get closer to your goal. I see you want to know where the money goes and save time so it should work for you like it did for me. I used to charge everything or write checks and then pay a big visa bill. My problem was I never knew exactly how much I spent because neither Visa or check writing are record systems. They just generate transactions records. I made it a goal use online banking to match my spending to the available cash and ended up ok usually 9-10 months out of the year. I started with direct deposit of my paycheck. Each Saturday, I sit down and within a half hour, I've paid the bills for the week and know where I stand for the following week. Any new bill that comes in, I add it to online banking even if it's not a recurring expense. I also pull down cash from the ATM but just enough to allow me to do what I have to do. If it's more than $30 or $40 bucks, I use the debit card so that expense goes right to the online bank statement. My monthly bank statement gives me a single report with everything listed. Mortgage, utilities, car payment, cable bill, phone bill, insurance, newspaper, etc... It does not record these transactions in generic categories; they actually say Verizon or Comcast or Shop Rite. I found this serves as the only report I need to see what's happening with my budget. It may take a while to change to a plan like this one. but you'll now have a system that shows you in a single place where the money goes. Move all bills that are \"\"auto-pay\"\" to the online system and watch your Visa bill go down. The invested time is likely what you're doing now writing checks. Hope this helps.\"",
"title": ""
},
{
"docid": "457667",
"text": "I've been budgeting with MS Money since 2004 and was pretty disappointed to hear it's being discontinued. Budgeting is actually a stress-relieving hobby for me, and I can be a bit of a control-freak when it comes to finances, so I decided to start early looking for a replacement rather than waiting until MS Money can no longer download transactions. Here are the pros and cons of the ones I've tried (updated 10/2010): You Need A Budget Pro (YNAB) - Based on the old envelopes system, YNAB has you allot money from each paycheck to a specific budget category (envelope). It encourages you to live on last money's income, and if you have trouble with overspending, that can be a great plan. Personally, I'm a big believer in the envelope concept, so that's the biggest pro I found. Also, it's a downloaded software, so once I've bought it (for about $50) it's mine, without forced upgrades as far as I've seen. The big con for me was that it does not automatically download transactions. I would have to sign on to each institution's website and manually download to the program. Also, coming from Money, I'm used to having features that YNAB doesn't offer, like the ability to store information about my accounts. Overall, it's forward-thinking and a good budgeting system, but will take some extra time to download transactions and isn't really a comprehensive management tool for all my financial needs. You can try it out with their free trial. Mint - This is a free online program. The free part was a major pro. It also looks pretty, if that's important to you. Updating is automatic, once you've got it all set up, so that's a pro. Mint's budgeting tools are so-so. Basically, you choose a category and tell it your limit. It yells at you (by text or email) when you cross the line, but doesn't seem to offer any other incentive to stay on budget. When I first looked at Mint, it did not connect with my credit union, but it currently connects to all my banks and all but one of my student loan institutions. Another recent improvement is that Mint now allows you to manually add transactions, including pending checks and cash transactions. The cons for me are that it does not give me a good end-of-the-month report, doesn't allow me to enter details of my paychecks, and doesn't give me any cash-flow forecasting. Overall, Mint is a good casual, retrospective, free online tool, but doesn't allow for much planning ahead. Mvelopes - Here's another online option, but this one is subscription-based. Again, we find the old envelopes system, which I think is smart, so that's a pro for me. It's online, so it downloads transactions automatically, but also allows you to manually add transactions, so another pro. The big con on this one is the cost. Depending on how you far ahead you choose to pay (quarterly, yearly or biannually), you're paying $7.60 to $12 per month. They do offer a free trial for 14 days (plus another 14 days offered when you try to cancel). Another con is that they don't provide meaningful reports. Overall, a good concept, but not worth the cost for me. Quicken - I hadn't tried Quicken earlier because they don't offer a free trial, but after the last few fell short, I landed with Quicken 2009. Pro for Quicken, as an MS Money user is that it is remarkably similar in format and options. The registers and reports are nearly identical. One frustration I'd had with Money was that it was ridiculously slow at start-up, and after a year or so of entering data, Quicken is dragging. Con for Quicken, again as an MS Money user, is that it's budgeting is not as detailed as I would like. Also, it does not download transactions smoothly now that my banks all ask security questions as part of sign-in. I have to sign in to my bank's website and manually download. Quicken 2011 is out now, but I haven't tried it yet. Hopefully they've solved the problem of security questions. Quicken 2011 promises an improved cash-flow forecast, which sounds promising, and was a feature of MS Money that I have very much missed. Haven't decided yet if it's worth the $50 to upgrade to 2011.",
"title": ""
},
{
"docid": "548596",
"text": "For months prior to going public a company has to file financial documents with the SEC. These are available to the public at www.sec.gov on their Edgar database. For instance, Eagleline is listed as potentially IPOing next week. You can find out all the details of any IPO including correspondence between the company and the SEC on Edgar. Here's the link for Eagleline (disclaimer, I have not investigated this company. It is an example only) https://www.sec.gov/cgi-bin/browse-edgar?action=getcompany&CIK=0001675776&owner=exclude&count=40 The most important, complex, and thorough document is the initial registration statement, usually an S-1, and subsequent amendments that occur as a result of new information or SEC questions. You can often get insight into a new public company by looking at the changes that have occurred in amendments since their initial filings. I highly advise people starting out to first look at the filings of companies they work for or know the industry intimately. This will help you to better understand the filings from companies you may not be so familiar with. A word of caution. Markets and company filings are followed by very large numbers of smart people experienced in each business area so don't assume there is fast and easy money to be made. Still, you will be a bit ahead if you learn to read and understand the filings public companies are required to make.",
"title": ""
},
{
"docid": "291903",
"text": "\"Pink Sheets is not a stock exchange per se, and securities traded through it are not as \"\"safe\"\" as the ones on a stock exchange regulated by SEC. Many companies are traded there because they failed to comply with the SEC regulations, or are bankrupt or don't want the level of reporting to the public that the SEC regulations require. Since you're talking about an ADR of a company traded on LSE, it might be much safer that other, \"\"regular\"\", securities, but still it means that you're buying an unregulated security (even if it is of a company regulated elsewhere). Notice the volume of trades: mere thousands of dollars per day (in a good day, in some days there are no trades at all). It makes it harder to sell the security when needed. Why not buying at LSE?\"",
"title": ""
},
{
"docid": "534734",
"text": "\"Systemic and well know patterns in sales are priced in to the security. Typically companies with very cyclical earnings like this will issue guidance of earnings per share within a range. These expected earnings are priced in before the earnings are actually booked. If a company meets these expectations the stock will likely stay relatively flat. If the company misses this expectation, the stock, generally, will get slammed. This kind of Wall Street behavior typically mystifies media outlets when a company's stock declines after reporting a record high level of whatever metric. The record high is irrelevant if it misses the expectation. There is no crystal ball but if something is both well known and expected it's already been \"\"priced in.\"\" If the well known expected event doesn't occur, maybe it's a new normal.\"",
"title": ""
},
{
"docid": "220772",
"text": "\"The following is only an overview and does not contain all of the in-depth reasons why you should look more deeply. When you look at a stock's financials in depth you are looking for warning signs. These may warn of many things but one important thing to look for is ratio and growth rate manipulation. Using several different accounting methods it is possible to make a final report reflect a PE ratio (or any other ratio) that is inconsistent with the realities of the company's position. Earnings manipulation (in the way that Enron in particular manipulated them) is more widespread than you might think as \"\"earnings smoothing\"\" is a common way of keeping earnings in line (or smooth) in a recession or a boom. The reason that PE ratio looks so good could well be because professional investors have avoided the stock as there appear to be \"\"interesting\"\" (but legal) accounting decisions that are of concern. Another issue that you don't consider is growth. earnings may look good in the current reporting period but may have been stagnant or falling when considered over multiple periods. The low price may indicate falling revenues, earnings and market share that you would not be aware of when taking only your criteria into account. Understanding a firm will also give you an insight into how future news might affect the company. If the company has a lot of debt and market interest rates rise or fall how will that effect their debt, if another company brings out a competing product next week how will it effect the company? How will it effect their bottom line? How much do they rely on a single product line? How likely is it that their flagship product will become obsolete? How would that effect the company? Looking deeply into a company's financial statements will allow you to see any issues in their accounting practices and give you a feel for how they are preforming over time, it will also let you look into their cost of capital and investment decisions. Looking deeply into their products, company structure and how news will effect them will give you an understanding of potential issues that could threaten your investment before they occur. When looking for value you shouldn't just look at part of the value of the company; you wouldn't just look at sales of a single T-shirt range at Wallmart when deciding whether to invest in them. It is exactly the same argument for why you should look at the whole of the company's state when choosing to invest rather than a few small metrics.\"",
"title": ""
},
{
"docid": "156816",
"text": "The cause of incomplete/inaccurate financial data's appearing on free sites is that it is both complicated and expensive to obtain and parse these data. Even within a single country, different pieces of financial data are handled by different authorities. In the US, for example, there is one generally recognized authority for stock prices and volumes (CQS), but a completely different authority for corporate earnings data (SEC). For futures and options data the only authority is each individual exchange. Each of these sources might have a vastly different interface to their data; some may have websites, others may have FTPs, others may have TCP datastreams to which you must subscribe, etc. Now throw in the rest of the world and all their exchanges and regulatory agencies, and you can see how it's a difficult job to gather all this information, parse it on a daily (or more frequent) basis, and check it all for errors. There are some companies (e.g. Bloomberg) whose entire business model is to do the above. They spend tens of millions of dollars per year to support the infrastructure and manpower required to keep such a complex system working, and they charge their consumers a pretty penny in return. Do Google/Yahoo pay for Bloomberg data access just to display information that we then consume for free? Maybe. Maybe they pay for some less expensive reduced data set. Or a data set that is less rigorously checked for errors. Even if they pay for the best data available, there's no guarantee that a company's last earnings report didn't have a glitch in it, or that Bloomberg's latest download from the Canadian Agency for Corporate Dividends and Moose Census-Taking didn't get cut off in the middle, or that the folks at Yahoo built a robust system that can handle a particular file's not arriving on time. Bloomberg has dozens or even hundreds of employees focused on just this one task; Yahoo probably has 5. Moral: If you really need the best available data you must go to the source(s), or you must pay a provider to whom you can then complain when something is wrong. With free data you get what you pay for.",
"title": ""
},
{
"docid": "390529",
"text": "\"In the US, a private company with less than 500 owners can dictate who can or can't become a shareholder (this is true in general, but I'm sure there are loopholes). Prior to Google's IPO I could not buy shares in Google at any price. The reason Google was \"\"forced\"\" to go public is the 500 shareholder rule. At a high level, with 500 shareholders the company is forced to do some extra financial accounting and they no longer can control who owns a share of the company, allowing me to purchase shares of google at that point. At that point, it typically becomes in the companies best interest to go public. See this article about Google approaching the 500 shareholder limit in 2003. Further, Sorkin is not quite correct that \"\"securities laws mandate that the company go public\"\" if by \"\"go public\"\" we mean list on a stock exchange, available for general purchase. Securities laws mandate what has to be reported in financial reporting and when you have to report it. Securities laws also can dictate restrictions on ownership of stock and if a company can impose their own restrictions. A group of investors cannot force a company onto a stock exchange. If shares of Facebook are already for sale to anyone, then having >500 shareholders will force Facebook to file more paperwork with the SEC, it won't force Facebook onto the NYSE or NASDAQ. When that point is reached, it may be in Facebook's best interest to have an IPO, but they will not be required by law to do so. Update: CNN article discusses likely Facebook IPO in 2012. When companies have more than 500 shareholders, they're required to make significant financial disclosures -- though they can choose to remain private and keep their stock from trading publicly. However, most companies facing mandatory disclosures opt to go public. The Securities and Exchange Commission gives businesses lots of time to prepare for that milestone. Companies have until 120 days after the end of the fiscal year in which they cross the 500-shareholder line to begin making their disclosures. If Facebook tips the scale this year, that gives it until April 2012 to start filing financial reports.\"",
"title": ""
}
] |
714
|
Low expression of miR7a does not repress target genes or exert a biological function in testis.
|
[
{
"docid": "18421962",
"text": "Recent studies have reported that competitive endogenous RNAs (ceRNAs) can act as sponges for a microRNA (miRNA) through their binding sites and that changes in ceRNA abundances from individual genes can modulate the activity of miRNAs. Consideration of this hypothesis would benefit from knowing the quantitative relationship between a miRNA and its endogenous target sites. Here, we altered intracellular target site abundance through expression of an miR-122 target in hepatocytes and livers and analyzed the effects on miR-122 target genes. Target repression was released in a threshold-like manner at high target site abundance (≥1.5 × 10(5) added target sites per cell), and this threshold was insensitive to the effective levels of the miRNA. Furthermore, in response to extreme metabolic liver disease models, global target site abundance of hepatocytes did not change sufficiently to affect miRNA-mediated repression. Thus, modulation of miRNA target abundance is unlikely to cause significant effects on gene expression and metabolism through a ceRNA effect.",
"title": "Assessing the ceRNA hypothesis with quantitative measurements of miRNA and target abundance."
}
] |
[
{
"docid": "15635366",
"text": "L3mbtl2 has been implicated in transcriptional repression and chromatin compaction but its biological function has not been defined. Here we show that disruption of L3mbtl2 results in embryonic lethality with failure of gastrulation. This correlates with compromised proliferation and abnormal differentiation of L3mbtl2(-/-) embryonic stem (ES) cells. L3mbtl2 regulates genes by recruiting a Polycomb Repressive Complex1 (PRC1)-related complex, resembling the previously described E2F6-complex, and including G9A, Hdac1, and Ring1b. The presence of L3mbtl2 at target genes is associated with H3K9 dimethylation, low histone acetylation, and H2AK119 ubiquitination, but the latter is neither dependent on L3mbtl2 nor sufficient for repression. Genome-wide studies revealed that the L3mbtl2-dependent complex predominantly regulates genes not bound by canonical PRC1 and PRC2. However, some developmental regulators are repressed by the combined activity of all three complexes. Together, we have uncovered a highly selective, essential role for an atypical PRC1-family complex in ES cells and early development.",
"title": "The polycomb group protein L3mbtl2 assembles an atypical PRC1-family complex that is essential in pluripotent stem cells and early development."
},
{
"docid": "6828370",
"text": "The canonical role of messenger RNA (mRNA) is to deliver protein-coding information to sites of protein synthesis. However, given that microRNAs bind to RNAs, we hypothesized that RNAs could possess a regulatory role that relies on their ability to compete for microRNA binding, independently of their protein-coding function. As a model for the protein-coding-independent role of RNAs, we describe the functional relationship between the mRNAs produced by the PTEN tumour suppressor gene and its pseudogene PTENP1 and the critical consequences of this interaction. We find that PTENP1 is biologically active as it can regulate cellular levels of PTEN and exert a growth-suppressive role. We also show that the PTENP1 locus is selectively lost in human cancer. We extended our analysis to other cancer-related genes that possess pseudogenes, such as oncogenic KRAS. We also demonstrate that the transcripts of protein-coding genes such as PTEN are biologically active. These findings attribute a novel biological role to expressed pseudogenes, as they can regulate coding gene expression, and reveal a non-coding function for mRNAs.",
"title": "A coding-independent function of gene and pseudogene mRNAs regulates tumour biology"
},
{
"docid": "18895793",
"text": "The relationship between chromatin structure and gene expression is a subject of intense study. The universal transcriptional activator Gal4 removes promoter nucleosomes as it triggers transcription, but how it does so has remained obscure. The reverse process, repression of transcription, has often been correlated with the presence of nucleosomes. But it is not known whether nucleosomes are required for that effect. A new quantitative assay describes, for any given location, the fraction of DNA molecules in the population that bears a nucleosome at any given instant. This allows us to follow the time courses of nucleosome removal and reformation, in wild-type and mutant cells, upon activation (by galactose) and repression (by glucose) of the GAL genes of yeast. We show that upon being freed of its inhibitor Gal80 by the action of galactose, Gal4 quickly recruits SWI/SNF to the genes, and that nucleosome \"remodeler\" rapidly removes promoter nucleosomes. In the absence of SWI/SNF, Gal4's action also results in nucleosome removal and the activation of transcription, but both processes are significantly delayed. Addition of glucose to cells growing in galactose represses transcription. But if galactose remains present, Gal4 continues to work, recruiting SWI/SNF and maintaining the promoter nucleosome-free despite it being repressed. This requirement for galactose is obviated in a mutant in which Gal4 works constitutively. These results show how an activator's recruiting function can control chromatin structure both during gene activation and repression. Thus, both under activating and repressing conditions, the activator can recruit an enzymatic machine that removes promoter nucleosomes. Our results show that whereas promoter nucleosome removal invariably accompanies activation, reformation of nucleosomes is not required for repression. The finding that there are two routes to nucleosome removal and activation of transcription-one that requires the action of SWI/SNF recruited by the activator, and a slower one that does not-clarifies our understanding of the early events of gene activation, and in particular corrects earlier reports that SWI/SNF plays no role in GAL gene induction. Our finding that chromatin structure is irrelevant for repression as studied here-that is, repression sets in as efficiently whether or not promoter nucleosomes are allowed to reform-contradicts the widely held, but little tested, idea that nucleosomes are required for repression. These findings were made possible by our nucleosome occupancy assay. The assay, we believe, will prove useful in studying other outstanding issues in the field.",
"title": "Activator Control of Nucleosome Occupancy in Activation and Repression of Transcription"
},
{
"docid": "6820680",
"text": "MicroRNAs (miRNAs) are short noncoding RNAs that exert posttranscriptional gene silencing and regulate gene expression. In addition to the hundreds of conserved cellular miRNAs that have been identified, miRNAs of viral origin have been isolated and found to modulate both the viral life cycle and the cellular transcriptome. Thus far, detection of virus-derived miRNAs has been largely limited to DNA viruses, suggesting that RNA viruses may be unable to exploit this aspect of transcriptional regulation. Lack of RNA virus-produced miRNAs has been attributed to the replicative constraints that would incur following RNase III processing of a genomic hairpin. To ascertain whether the generation of viral miRNAs is limited to DNA viruses, we investigated whether influenza virus could be designed to deliver functional miRNAs without affecting replication. Here, we describe a modified influenza A virus that expresses cellular microRNA-124 (miR-124). Insertion of the miR-124 hairpin into an intron of the nuclear export protein transcript resulted in endogenous processing and functional miR-124. We demonstrate that a viral RNA genome incorporating a hairpin does not result in segment instability or miRNA-mediated genomic targeting, thereby permitting the virus to produce a miRNA without having a negative impact on viral replication. This work demonstrates that RNA viruses can produce functional miRNAs and suggests that this level of transcriptional regulation may extend beyond DNA viruses.",
"title": "Engineered RNA viral synthesis of microRNAs."
},
{
"docid": "10024681",
"text": "Deregulation of microRNA (miRNA) expression can have a critical role in carcinogenesis. Here we show in prostate cancer that miRNA-205 (miR-205) transcription is commonly repressed and the MIR-205 locus is hypermethylated. LOC642587, the MIR-205 host gene of unknown function, is also concordantly inactivated. We show that miR-205 targets mediator 1 (MED1, also called TRAP220 and PPARBP) for transcriptional silencing in normal prostate cells, leading to reduction in MED1 mRNA levels, and in total and active phospho-MED1 protein. Overexpression of miR-205 in prostate cancer cells negatively affects cell viability, consistent with a tumor suppressor function. We found that hypermethylation of the MIR-205 locus was strongly related with a decrease in miR-205 expression and an increase in MED1 expression in primary tumor samples (n=14), when compared with matched normal prostate (n=7). An expanded patient cohort (tumor n=149, matched normal n=30) also showed significant MIR-205 DNA methylation in tumors compared with normal, and MIR-205 hypermethylation is significantly associated with biochemical recurrence (hazard ratio=2.005, 95% confidence interval (1.109, 3.625), P=0.02), in patients with low preoperative prostate specific antigen. In summary, these results suggest that miR-205 is an epigenetically regulated tumor suppressor that targets MED1 and may provide a potential biomarker in prostate cancer management.",
"title": "Epigenetic-induced repression of microRNA-205 is associated with MED1 activation and a poorer prognosis in localized prostate cancer"
},
{
"docid": "16550075",
"text": "BCL-6, a transcriptional repressor frequently translocated in lymphomas, regulates germinal center B cell differentiation and inflammation. DNA microarray screening identified genes repressed by BCL-6, including many lymphocyte activation genes, suggesting that BCL-6 modulates B cell receptor signals. BCL-6 repression of two chemokine genes, MIP-1alpha and IP-10, may also attenuate inflammatory responses. Blimp-1, another BCL-6 target, is important for plasmacytic differentiation. Since BCL-6 expression is silenced in plasma cells, repression of blimp-1 by BCL-6 may control plasmacytic differentiation. Indeed, inhibition of BCL-6 function initiated changes indicative of plasmacytic differentiation, including decreased expression of c-Myc and increased expression of the cell cycle inhibitor p27kip1. These data suggest that malignant transformation by BCL-6 involves inhibition of differentiation and enhanced proliferation.",
"title": "BCL-6 represses genes that function in lymphocyte differentiation, inflammation, and cell cycle control."
},
{
"docid": "23581096",
"text": "The SRY gene on the mammalian Y chromosome undoubtedly acts to determine testis, but it is still quite unclear how. It was originally supposed that SRY acts directly to activate other genes in the testis-determining pathway. This paper presents an alternative hypothesis that SRY functions indirectly, by interacting with related genes SOX3 (from which SRY evolved) and SOX9 (which appears to be intimately involved in vertebrate gonad differentiation). Specifically, I propose that in females SOX3 inhibits SOX9 function, but in males, SRY inhibits SOX3 and permits SOX9 to enact its testis-determining role. This hypothesis makes testable predictions of the phenotypes of XX and XY individuals with deficiencies or overproduction of any of the three genes, and is able to account for the difficult cases of XX(SRY-) males and transdifferentiation in the absence of SRY. The hypothesis also suggests a way that the dominant SRY sex-determining system of present-day mammals may have evolved from an ancient system relying on SOX3 dosage.",
"title": "Interactions between SRY and SOX genes in mammalian sex determination."
},
{
"docid": "20028729",
"text": "Nuclear receptors regulate many biologically important processes in development and homeostasis by their bimodal function as repressors and activators of gene transcription. A finely tuned modulation of the transcriptional activities of nuclear receptors is crucial for determining highly specific and diversified programmes of gene expression. Recent studies have provided insights into the molecular mechanisms that are required to switch between repression and activation functions, the combinatorial roles of the multiple cofactor complexes that are required for mediating transcriptional regulation, and the central question of how several different signalling pathways can be integrated at the nuclear level to achieve specific profiles of gene expression.",
"title": "Controlling nuclear receptors: the circular logic of cofactor cycles"
},
{
"docid": "2000038",
"text": "MicroRNAs (miRNAs) are short, highly conserved noncoding RNA molecules that repress gene expression in a sequence-dependent manner. We performed single-cell measurements using quantitative fluorescence microscopy and flow cytometry to monitor a target gene's protein expression in the presence and absence of regulation by miRNA. We find that although the average level of repression is modest, in agreement with previous population-based measurements, the repression among individual cells varies dramatically. In particular, we show that regulation by miRNAs establishes a threshold level of target mRNA below which protein production is highly repressed. Near this threshold, protein expression responds sensitively to target mRNA input, consistent with a mathematical model of molecular titration. These results show that miRNAs can act both as a switch and as a fine-tuner of gene expression.",
"title": "MicroRNAs can generate thresholds in target gene expression"
},
{
"docid": "6455142",
"text": "Although regulation of histone methylation is believed to contribute to embryonic stem cell (ESC) self-renewal, the mechanisms remain obscure. We show here that the histone H3 trimethyl lysine 4 (H3K4me3) demethylase, KDM5B, is a downstream Nanog target and critical for ESC self-renewal. Although KDM5B is believed to function as a promoter-bound repressor, we find that it paradoxically functions as an activator of a gene network associated with self-renewal. ChIP-Seq reveals that KDM5B is predominantly targeted to intragenic regions and that it is recruited to H3K36me3 via an interaction with the chromodomain protein MRG15. Depletion of KDM5B or MRG15 increases intragenic H3K4me3, increases cryptic intragenic transcription, and inhibits transcriptional elongation of KDM5B target genes. We propose that KDM5B activates self-renewal-associated gene expression by repressing cryptic initiation and maintaining an H3K4me3 gradient important for productive transcriptional elongation.",
"title": "KDM5B regulates embryonic stem cell self-renewal and represses cryptic intragenic transcription."
},
{
"docid": "4434951",
"text": "BACKGROUND Age-associated epigenetic changes are implicated in aging. Notably, age-associated DNA methylation changes comprise a so-called aging \"clock\", a robust biomarker of aging. However, while genetic, dietary and drug interventions can extend lifespan, their impact on the epigenome is uncharacterised. To fill this knowledge gap, we defined age-associated DNA methylation changes at the whole-genome, single-nucleotide level in mouse liver and tested the impact of longevity-promoting interventions, specifically the Ames dwarf Prop1 df/df mutation, calorie restriction and rapamycin. RESULTS In wild-type mice fed an unsupplemented ad libitum diet, age-associated hypomethylation was enriched at super-enhancers in highly expressed genes critical for liver function. Genes harbouring hypomethylated enhancers were enriched for genes that change expression with age. Hypermethylation was enriched at CpG islands marked with bivalent activating and repressing histone modifications and resembled hypermethylation in liver cancer. Age-associated methylation changes are suppressed in Ames dwarf and calorie restricted mice and more selectively and less specifically in rapamycin treated mice. CONCLUSIONS Age-associated hypo- and hypermethylation events occur at distinct regulatory features of the genome. Distinct longevity-promoting interventions, specifically genetic, dietary and drug interventions, suppress some age-associated methylation changes, consistent with the idea that these interventions exert their beneficial effects, in part, by modulation of the epigenome. This study is a foundation to understand the epigenetic contribution to healthy aging and longevity and the molecular basis of the DNA methylation clock.",
"title": "Diverse interventions that extend mouse lifespan suppress shared age-associated epigenetic changes at critical gene regulatory regions"
},
{
"docid": "15058155",
"text": "EBI2, aka GPR183, is a G-couple receptor originally identified in 1993 as one of main genes induced in Burkitt's lymphoma cell line BL41 by Epstein-Barr virus (EBV) infection. After it was reported in 2009 that the receptor played a key role in regulating B cell migration and responses, we initiated an effort in looking for its endogenous ligand. In 2011 we and another group reported the identification of 7α, 25-dihydroxyxcholesterol (7α, 25-OHC), an oxysterol, as the likely physiological ligand of EBI2. A few subsequently published studies further elucidated how 7α, 25-OHC bound to EBI2, and how a gradient of 7α, 25-OHC could be generated in vivo and regulated migration, activation, and functions of B cells, T cells, dendritic cells (DCs), monocytes/macrophages, and astrocytes. The identification of 7α, 25-OHC as a G protein-coupled receptor ligand revealed a previously unknown signaling system of oxysterols, a class of molecules which exert profound biological functions. Dysregulation of the synthesis or functions of these molecules is believed to contribute to inflammation and autoimmune diseases, cardiovascular diseases, neurodegenerative diseases, cancer as well as metabolic diseases such as diabetes, obesity, and dyslipidemia. Therefore EBI2 may represent a promising target for therapeutic interventions for human diseases.",
"title": "7α, 25-dihydroxycholesterol-mediated activation of EBI2 in immune regulation and diseases"
},
{
"docid": "21487212",
"text": "Ex-FABP, an extracellular fatty acid binding lipocalin, is physiologically expressed by differentiating chicken chondrocytes and myoblasts. Its expression is enhanced after cell treatment with inflammatory stimuli and repressed by anti-inflammatory agents, behaving as an acute phase protein. Chicken liver fragments in culture show enhanced protein expression after bacterial endotoxin treatment. To investigate the biological role of Ex-FABP, we stably transfected proliferating chondrocytes with an expression vector carrying antisense oriented Ex-FABP cDNA. We observed a dramatic loss of cell viability and a strong inhibition of cell proliferation and differentiation. When chondrocytes were transfected with the antisense oriented Ex-FABP cDNA we observed that Ex-FABP down-modulation increased apoptotic cell number. Myoblasts transfected with the same expression vector showed extensive cell death and impaired myotube formation. We suggest that Ex-FABP acts as a constitutive survival protein and that its expression and activation are fundamental to protect chondrocytes from cell death.",
"title": "Inhibition of cell proliferation and induction of apoptosis by ExFABP gene targeting."
},
{
"docid": "9159495",
"text": "Expression levels of many microRNAs (miRNAs) change during aging, notably declining globally in a number of organisms and tissues across taxa. However, little is known about the mechanisms or the biological relevance for this change. We investigated the network of genes that controls miRNA transcription and processing during C. elegans aging. We found that miRNA biogenesis genes are highly networked with transcription factors and aging-associated miRNAs. In particular, miR-71, known to influence life span and itself up-regulated during aging, represses alg-1/Argonaute expression post-transcriptionally during aging. Increased ALG-1 abundance in mir-71 loss-of-function mutants led to globally increased miRNA expression. Interestingly, these mutants demonstrated widespread mRNA expression dysregulation and diminished levels of variability both in gene expression and in overall life span. Thus, the progressive molecular decline often thought to be the result of accumulated damage over an organism's life may be partially explained by a miRNA-directed mechanism of age-associated decline.",
"title": "A microRNA feedback loop regulates global microRNA abundance during aging."
},
{
"docid": "37204802",
"text": "Jumonji domain-containing 6 (JMJD6) is a member of the Jumonji C domain-containing family of proteins. Compared to other members of the family, the cellular activity of JMJD6 is still not clearly defined and its biological function is still largely unexplored. Here we report that JMJD6 is physically associated with the tumor suppressor p53. We demonstrated that JMJD6 acts as an α-ketoglutarate- and Fe(II)-dependent lysyl hydroxylase to catalyze p53 hydroxylation. We found that p53 indeed exists as a hydroxylated protein in vivo and that the hydroxylation occurs mainly on lysine 382 of p53. We showed that JMJD6 antagonizes p53 acetylation, promotes the association of p53 with its negative regulator MDMX, and represses transcriptional activity of p53. Depletion of JMJD6 enhances p53 transcriptional activity, arrests cells in the G1 phase, promotes cell apoptosis, and sensitizes cells to DNA damaging agent-induced cell death. Importantly, knockdown of JMJD6 represses p53-dependent colon cell proliferation and tumorigenesis in vivo, and significantly, the expression of JMJD6 is markedly up-regulated in various types of human cancer especially in colon cancer, and high nuclear JMJD6 protein is strongly correlated with aggressive clinical behaviors of colon adenocarcinomas. Our results reveal a novel posttranslational modification for p53 and support the pursuit of JMJD6 as a potential biomarker for colon cancer aggressiveness and a potential target for colon cancer intervention.",
"title": "JMJD6 Promotes Colon Carcinogenesis through Negative Regulation of p53 by Hydroxylation"
},
{
"docid": "14380875",
"text": "Glucocorticoids repress NFkappaB-mediated activation of proinflammatory genes such as interleukin-8 (IL-8) and ICAM-1. Our experiments suggest that the glucocorticoid receptor (GR) confers this effect by associating through protein-protein interactions with NFkappaB bound at each of these genes. That is, we show that the GR zinc binding region (ZBR), which includes the DNA binding and dimerization functions of the receptor, binds directly to the dimerization domain of the RelA subunit of NFkappaB in vitro and that the ZBR is sufficient to associate with RelA bound at NFkappaB response elements in vivo. Moreover, we demonstrate in vivo and in vitro that GR does not disrupt DNA binding by NFkappaB. In transient transfections, we found that the GR ligand binding domain is essential for repression of NFkappaB but not for association with it and that GR can repress an NFkappaB derivative bearing a heterologous activation domain. We used chromatin immunoprecipitation assays in untransfected A549 cells to infer the mechanism by which the tethered GR represses NFkappaB-activated transcription. As expected, we found that the inflammatory signal TNFalpha stimulated preinitiation complex (PIC) assembly at the IL-8 and ICAM-1 promoters and that the largest subunit of RNA polymerase II (pol II) in those complexes became phosphorylated at serines 2 and 5 in its carboxy-terminal domain (CTD) heptapeptide repeats (YSPTSPS); these modifications are required for transcription initiation. Remarkably, GR did not inhibit PIC assembly under repressing conditions, but rather interfered with phosphorylation of serine 2 of the pol II CTD.",
"title": "The Glucocorticoid Receptor Inhibits"
},
{
"docid": "43156471",
"text": "We have conducted a genomewide investigation into the enzymatic specificity, expression profiles, and binding locations of four histone deacetylases (HDACs), representing the three different phylogenetic classes in fission yeast (Schizosaccharomyces pombe). By directly comparing nucleosome density, histone acetylation patterns and HDAC binding in both intergenic and coding regions with gene expression profiles, we found that Sir2 (class III) and Hos2 (class I) have a role in preventing histone loss; Clr6 (class I) is the principal enzyme in promoter-localized repression. Hos2 has an unexpected role in promoting high expression of growth-related genes by deacetylating H4K16Ac in their open reading frames. Clr3 (class II) acts cooperatively with Sir2 throughout the genome, including the silent regions: rDNA, centromeres, mat2/3 and telomeres. The most significant acetylation sites are H3K14Ac for Clr3 and H3K9Ac for Sir2 at their genomic targets. Clr3 also affects subtelomeric regions which contain clustered stress- and meiosis-induced genes. Thus, this combined genomic approach has uncovered different roles for fission yeast HDACs at the silent regions in repression and activation of gene expression.",
"title": "Genomewide analysis of nucleosome density histone acetylation and HDAC function in fission yeast."
},
{
"docid": "13777706",
"text": "Polycomb repressor complexes (PRCs) are important chromatin modifiers fundamentally implicated in pluripotency and cancer. Polycomb silencing in embryonic stem cells (ESCs) can be accompanied by active chromatin and primed RNA polymerase II (RNAPII), but the relationship between PRCs and RNAPII remains unclear genome-wide. We mapped PRC repression markers and four RNAPII states in ESCs using ChIP-seq, and found that PRC targets exhibit a range of RNAPII variants. First, developmental PRC targets are bound by unproductive RNAPII (S5p(+)S7p(-)S2p(-)) genome-wide. Sequential ChIP, Ring1B depletion, and genome-wide correlations show that PRCs and RNAPII-S5p physically bind to the same chromatin and functionally synergize. Second, we identify a cohort of genes marked by PRC and elongating RNAPII (S5p(+)S7p(+)S2p(+)); they produce mRNA and protein, and their expression increases upon PRC1 knockdown. We show that this group of PRC targets switches between active and PRC-repressed states within the ESC population, and that many have roles in metabolism.",
"title": "Polycomb Associates Genome-wide with a Specific RNA Polymerase II Variant, and Regulates Metabolic Genes in ESCs"
},
{
"docid": "18358026",
"text": "Cancer cells simultaneously harbor global losses and gains in DNA methylation. We demonstrate that inducing cellular oxidative stress by hydrogen peroxide treatment recruits DNA methyltransferase 1 (DNMT1) to damaged chromatin. DNMT1 becomes part of a complex(es) containing DNMT3B and members of the polycomb repressive complex 4. Hydrogen peroxide treatment causes relocalization of these proteins from non-GC-rich to GC-rich areas. Key components are similarly enriched at gene promoters in an in vivo colitis model. Although high-expression genes enriched for members of the complex have histone mark and nascent transcription changes, CpG island-containing low-expression genes gain promoter DNA methylation. Thus, oxidative damage induces formation and relocalization of a silencing complex that may explain cancer-specific aberrant DNA methylation and transcriptional silencing.",
"title": "Oxidative damage targets complexes containing DNA methyltransferases, SIRT1, and polycomb members to promoter CpG Islands."
},
{
"docid": "9752604",
"text": "In light of the emerging interplay between redox and metabolic signaling pathways we investigated the potential cross talk between nuclear factor E2-related factor 2 (Nrf2) and AMP-activated kinase (AMPK), central regulators of the cellular redox and energy balance, respectively. Making use of xanthohumol (XN) as an activator of both the AMPK and the Nrf2 signaling pathway we show that AMPK exerts a positive influence on Nrf2/heme oxygenase (HO)-1 signaling in mouse embryonic fibroblasts. Genetic ablation and pharmacological inhibition of AMPK blunts Nrf2-dependent HO-1 expression by XN already at the mRNA level. XN leads to AMPK activation via interference with mitochondrial function and activation of liver kinase B1 as upstream AMPK kinase. The subsequent AMPK-mediated enhancement of the Nrf2/HO-1 response does not depend on inhibition of the mammalian target of rapamycin, inhibition of glycogen synthase kinase 3β, or altered abundance of Nrf2 (total and nuclear). However, reduced endoplasmic reticulum stress was identified and elaborated as a step in the AMPK-augmented Nrf2/HO-1 response. Overall, we shed more light on the hitherto incompletely understood cross talk between the LKB1/AMPK and the Nrf2/HO-1 axis revealing for the first time involvement of the unfolded protein response as an additional player and suggesting tight cooperation between signaling pathways controlling cellular redox, energy, or protein homeostasis.",
"title": "Activated AMPK boosts the Nrf2/HO-1 signaling axis—A role for the unfolded protein response"
},
{
"docid": "4455466",
"text": "Recognition of modified histones by ‘reader’ proteins plays a critical role in the regulation of chromatin. H3K36 trimethylation (H3K36me3) is deposited onto the nucleosomes in the transcribed regions after RNA polymerase II elongation. In yeast, this mark in turn recruits epigenetic regulators to reset the chromatin to a relatively repressive state, thus suppressing cryptic transcription. However, much less is known about the role of H3K36me3 in transcription regulation in mammals. This is further complicated by the transcription-coupled incorporation of the histone variant H3.3 in gene bodies. Here we show that the candidate tumour suppressor ZMYND11 specifically recognizes H3K36me3 on H3.3 (H3.3K36me3) and regulates RNA polymerase II elongation. Structural studies show that in addition to the trimethyl-lysine binding by an aromatic cage within the PWWP domain, the H3.3-dependent recognition is mediated by the encapsulation of the H3.3-specific ‘Ser 31’ residue in a composite pocket formed by the tandem bromo–PWWP domains of ZMYND11. Chromatin immunoprecipitation followed by sequencing shows a genome-wide co-localization of ZMYND11 with H3K36me3 and H3.3 in gene bodies, and its occupancy requires the pre-deposition of H3.3K36me3. Although ZMYND11 is associated with highly expressed genes, it functions as an unconventional transcription co-repressor by modulating RNA polymerase II at the elongation stage. ZMYND11 is critical for the repression of a transcriptional program that is essential for tumour cell growth; low expression levels of ZMYND11 in breast cancer patients correlate with worse prognosis. Consistently, overexpression of ZMYND11 suppresses cancer cell growth in vitro and tumour formation in mice. Together, this study identifies ZMYND11 as an H3.3-specific reader of H3K36me3 that links the histone-variant-mediated transcription elongation control to tumour suppression.",
"title": "ZMYND11 links histone H3.3K36me3 to transcription elongation and tumour suppression"
},
{
"docid": "7645565",
"text": "Hepatitis B X protein (HBx) plays an essential role in the hepatitis B virus (HBV) replication cycle, but the function of HBx has been elusive until recently. It was recently shown that transcription from the HBV genome (covalently-closed circular DNA, cccDNA) is inhibited by the structural maintenance of chromosome 5/6 complex (Smc5/6), and that a key function of HBx is to redirect the DNA-damage binding protein 1 (DDB1) E3 ubiquitin ligase to target this complex for degradation. By doing so, HBx alleviates transcriptional repression by Smc5/6 and stimulates HBV gene expression. In this review, we discuss in detail how the interplay between HBx and Smc5/6 was identified and characterized. We also discuss what is known regarding the repression of cccDNA transcription by Smc5/6, the timing of HBx expression, and the potential role of HBx in promoting hepatocellular carcinoma (HCC).",
"title": "Identifying and Characterizing Interplay between Hepatitis B Virus X Protein and Smc5/6"
},
{
"docid": "18882947",
"text": "The HMG-box factor Tcf1 is required during T-cell development in the thymus and mediates the nuclear response to Wnt signals. Tcf1(-/-) mice have previously been characterized and show developmental blocks at the CD4-CD8- double negative (DN) to CD4+CD8+ double positive transition. Due to the blocks in T-cell development, Tcf1(-/-) mice normally have a very small thymus. Unexpectedly, a large proportion of Tcf1(-/-) mice spontaneously develop thymic lymphomas with 50% of mice developing a thymic lymphoma/leukemia at the age of 16 wk. These lymphomas are clonal, highly metastatic, and paradoxically show high Wnt signaling when crossed with Wnt reporter mice and have high expression of Wnt target genes Lef1 and Axin2. In wild-type thymocytes, Tcf1 is higher expressed than Lef1, with a predominance of Wnt inhibitory isoforms. Loss of Tcf1 as repressor of Lef1 leads to high Wnt activity and is the initiating event in lymphoma development, which is exacerbated by activating Notch1 mutations. Thus, Notch1 and loss of Tcf1 functionally act as collaborating oncogenic events. Tcf1 deficiency predisposes to the development of thymic lymphomas by ectopic up-regulation of Lef1 due to lack of Tcf1 repressive isoforms and frequently by cooperating activating mutations in Notch1. Tcf1 therefore functions as a T-cell-specific tumor suppressor gene, besides its established role as a Wnt responsive transcription factor. Thus, Tcf1 acts as a molecular switch between proliferative and repressive signals during T-lymphocyte development in the thymus.",
"title": "The Nuclear Effector of Wnt-Signaling, Tcf1, Functions as a T-Cell–Specific Tumor Suppressor for Development of Lymphomas"
},
{
"docid": "23356816",
"text": "The mammalian A-type cyclin family consists of two members, cyclin A1 (encoded by Ccna1) and cyclin A2 (encoded by Ccna2). Cyclin A2 promotes both G1/S and G2/M transitions, and targeted deletion of Ccna2 in mouse is embryonic lethal. Cyclin A1 is expressed in mice exclusively in the germ cell lineage and is expressed in humans at highest levels in the testis and certain myeloid leukaemia cells. To investigate the role of cyclin A1 and possible redundancy among the cyclins in vivo, we generated mice bearing a null mutation of Ccna1. Ccna1-/- males were sterile due to a block of spermatogenesis before the first meiotic division, whereas females were normal. Meiosis arrest in Ccna1–/– males was associated with increased germ cell apoptosis, desynapsis abnormalities and reduction of Cdc2 kinase activation at the end of meiotic prophase. Cyclin A1 is therefore essential for spermatocyte passage into the first meiotic division in male mice, a function that cannot be complemented by the concurrently expressed B-type cyclins.",
"title": "Cyclin A1 is required for meiosis in the male mouse"
},
{
"docid": "8909176",
"text": "Maltose metabolism of baker's yeast (Saccharomyces cerevisiae) in lean dough is negatively influenced by glucose repression, thereby delaying the dough fermentation. To improve maltose metabolism and leavening ability, it is necessary to alleviate glucose repression. The Snf1 protein kinase is well known to be essential for the response to glucose repression and required for transcription of glucose-repressed genes including the maltose-utilization genes (MAL). In this study, the SNF1 overexpression and deletion industrial baker's yeast strains were constructed and characterized in terms of maltose utilization, growth and fermentation characteristics, mRNA levels of MAL genes (MAL62 encoding the maltase and MAL61 encoding the maltose permease) and maltase and maltose permease activities. Our results suggest that overexpression of SNF1 was effective to glucose derepression for enhancing MAL expression levels and enzymes (maltase and maltose permease) activities. These enhancements could result in an 18% increase in maltose metabolism of industrial baker's yeast in LSMLD medium (the low sugar model liquid dough fermentation medium) containing glucose and maltose and a 15% increase in leavening ability in lean dough. These findings provide a valuable insight of breeding industrial baker's yeast for rapid fermentation.",
"title": "Effects of SNF1 on Maltose Metabolism and Leavening Ability of Baker's Yeast in Lean Dough."
},
{
"docid": "8331432",
"text": "The transcription factor HNF3 and linker histones H1 and H5 possess winged-helix DNA-binding domains, yet HNF3 and other fork head-related proteins activate genes during development whereas linker histones compact DNA in chromatin and repress gene expression. We compared how the two classes of factors interact with chromatin templates and found that HNF3 binds DNA at the side of nucleosome cores, similarly to what has been reported for linker histone. A nucleosome structural binding site for HNF3 is occupied at the albumin transcriptional enhancer in active and potentially active chromatin, but not in inactive chromatin in vivo. While wild-type HNF3 protein does not compact DNA extending from the nucleosome, as does linker histone, site-directed mutants of HNF3 can compact nucleosomal DNA if they contain basic amino acids at positions previously shown to be essential for nucleosomal DNA compaction by linker histones. The results illustrate how transcription factors can possess special nucleosome-binding activities that are not predicted from studies of factor interactions with free DNA.",
"title": "Binding of the winged-helix transcription factor HNF3 to a linker histone site on the nucleosome."
},
{
"docid": "12652963",
"text": "MicroRNAs (miRNAs) are ∼22 nt non-coding RNAs that typically bind to the 3' UTR of target mRNAs in the cytoplasm, resulting in mRNA destabilization and translational repression. Here, we report that miRNAs can also regulate gene expression by targeting non-coding antisense transcripts in human cells. Specifically, we show that miR-671 directs cleavage of a circular antisense transcript of the Cerebellar Degeneration-Related protein 1 (CDR1) locus in an Ago2-slicer-dependent manner. The resulting downregulation of circular antisense has a concomitant decrease in CDR1 mRNA levels, independently of heterochromatin formation. This study provides the first evidence for non-coding antisense transcripts as functional miRNA targets, and a novel regulatory mechanism involving a positive correlation between mRNA and antisense circular RNA levels.",
"title": "miRNA-dependent gene silencing involving Ago2-mediated cleavage of a circular antisense RNA."
},
{
"docid": "37438296",
"text": "Age-dependent decline in skeletal muscle function leads to several inherited and acquired muscular disorders in elderly individuals. The levels of microRNAs (miRNAs) could be altered during muscle maintenance and repair. We therefore performed a comprehensive investigation for miRNAs from five different periods of bovine skeletal muscle development using next-generation small RNA sequencing. In total, 511 miRNAs, including one putatively novel miRNA, were identified. Thirty-six miRNAs were differentially expressed between prenatal and postnatal stages of muscle development including several myomiRs (miR-1, miR-206 and let-7 families). Compared with miRNA expression between different muscle tissues, 14 miRNAs were up-regulated and 22 miRNAs were down-regulated in the muscle of postnatal stage. In addition, a novel miRNA was predicted and submitted to the miRBase database as bta-mir-10020. A dual luciferase reporter assay was used to demonstrate that bta-mir-10020 directly targeted the 3'-UTR of the bovine ANGPT1 gene. The overexpression of bta-mir-10020 significantly decreased the DsRed fluorescence in the wild-type expression cassette compared to the mutant type. Using three computational approaches - miranda, pita and rnahybrid - these differentially expressed miRNAs were also predicted to target 3609 bovine genes. Disease and biological function analyses and the KEGG pathway analysis revealed that these targets were statistically enriched in functionality for muscle growth and disease. Our miRNA expression analysis findings from different states of muscle development and aging significantly expand the repertoire of bovine miRNAs now shown to be expressed in muscle and could contribute to further studies on growth and developmental disorders in this tissue type.",
"title": "Altered microRNA expression in bovine skeletal muscle with age."
},
{
"docid": "27949347",
"text": "TP53 is the most frequently mutated gene in human cancer. Functionally, p53 is activated by a host of stress stimuli and, in turn, governs an exquisitely complex anti-proliferative transcriptional program that touches upon a bewildering array of biological responses. Despite the many unveiled facets of the p53 network, a clear appreciation of how and in what contexts p53 exerts its diverse effects remains unclear. How can we interpret p53's disparate activities and the consequences of its dysfunction to understand how cell type, mutation profile, and epigenetic cell state dictate outcomes, and how might we restore its tumor-suppressive activities in cancer?",
"title": "Putting p53 in Context"
},
{
"docid": "31882215",
"text": "We describe robust induction of autophagy during the reprogramming of mouse fibroblasts to induced pluripotent stem cells by four reprogramming factors (Sox2, Oct4, Klf4 and c-Myc), henceforth 4F. This process occurs independently of p53 activation, and is mediated by the synergistic downregulation of mechanistic target of rapamycin complex 1 (mTORC1) and the induction of autophagy-related genes. The 4F coordinately repress mTORC1, but bifurcate in their regulation of autophagy-related genes, with Klf4 and c-Myc inducing them but Sox2 and Oct4 inhibiting them. On one hand, inhibition of mTORC1 facilitates reprogramming by promoting cell reshaping (mitochondrial remodelling and cell size reduction). On the other hand, mTORC1 paradoxically impairs reprogramming by triggering autophagy. Autophagy does not participate in cell reshaping in reprogramming but instead degrades p62, whose accumulation in autophagy-deficient cells facilitates reprogramming. Our results thus reveal a complex signalling network involving mTORC1 inhibition and autophagy induction in the early phase of reprogramming, whose delicate balance ultimately determines reprogramming efficiency.",
"title": "Autophagy and mTORC1 regulate the stochastic phase of somatic cell reprogramming"
}
] |
4900
|
How to calculate lump sum required to generate desired monthly income?
|
[
{
"docid": "477062",
"text": "The product you seek is called a fixed immediate annuity. You also want to be clear it's inflation adjusted. In the US, the standard fixed annuity for a 40year old male (this is the lowest age I find on the site I use) has a 4.6% return. $6000/ yr means one would pay about $130,000 for this. The cost to include the inflation adder is about 50%, from what I recall. So close to $200,000. This is an insurance product, by the way, and you need to contact a local provider to get a better quote.",
"title": ""
}
] |
[
{
"docid": "254245",
"text": "What's the present value of using the payment plan? In all common sense the present value of a loan is the value that you can pay in the present to avoid taking a loan, which in this case is the lump sum payment of $2495. That rather supposes the question is a trick, providing irrelevant information about the stock market. However, if some strange interpretation is required which ignores the lump sum and wants to know how much you need in the present to pay the loan while being able to make 8% on the stock market that can be done. I will initially assume that since the lender's APR works out about 9.6% per month that the 8% from the stock market is also per month, but will also calculate for 8% annual effective and an 8% annual nominal rate. The calculation If you have $x in hand (present value) and it is exactly enough to take the loan while investing in the stock market, the value in successive months is $x plus the market return less the loan payment. In the third month the loan is paid down so the balance is zero. I.e. So the present value of using the payment plan while investing is $2569.37. You would need $2569.37 to cover the loan while investing, which is more than the $2495 lump sum payment requires. Therefore, it would be advisable to make the lump sum payment because it is less expensive: If you have $2569.37 in hand it would be best to pay the lump sum and invest the remaining $74.37 in the stock market. Otherwise you invest $2569.37 (initially), pay the loan and end up with $0 in three months. One might ask, what rate of return would the stock market need to yield to make it worth taking the loan? The APR proposed by the loan can be calculated. The present value of a loan is equal to the sum of the payments discounted to present value. I.e. with ∴ by induction So by comparing the $2495 lump sum payment with $997 over 3 x monthly instalments the interest rate implied by the loan can be found. Solving for r If you could obtain 9.64431% per month on the stock market the $x cash in hand required would be calculated by This is equal to the lump sum payment, so the calculated interest is comparable to the stock market rate of return. If you could gain more than 9.64431% per month on the stock market it would be better to invest and take the loan. Recurrence Form Solving the recurrence form shows the calculation is equivalent to the loan formula, e.g. becomes v[m + 1] = (1 + y) v[m] - p where v[0] = pv where In the final month v[final] = 0, i.e. when m = 3 Compare with the earlier loan formula: s = (d - d (1 + r)^-n) / r They are exactly equivalent, which is quite interesting, (because it wasn't immediately obvious to me that what the lender charges is the mirror opposite of what you gain by investing). The present value can be now be calculated using the formula. Still assuming the 8% stock market return is per month. If the stock market yield is 8% per annum effective rate and if it is given as a nominal annual yield, 8% compounded monthly",
"title": ""
},
{
"docid": "4734",
"text": "First let's define some terms. Your accrued benefit is a monthly benefit payable at your normal retirement age (usually 65). It is usually a life-only benefit but may have a number of years guaranteed or may have a survivor piece. It is defined by a plan formula (ie, it is a defined benefit). A lump sum is how much that accrued benefit is worth right now. Lump sums are based on applicable interest rates and mortality tables specified by the IRS (interest rates are released monthly, mortality annually). Your plan can either use the same interest rates for a whole year, or they can use new ones each month. Affecting your lump sum is whether your accrued benefit is payable now (immediately, you are age 65), or later (deferred, you are now age 30). For example, instead of being paid an annuity assume you are paid just one payment of $1,000 on your 65th birthday. The lump sum of that for a 65 year old would be $1,000 since there would be no interest discount, and no chance of dying before payment. For a 30 year old, at 4% interest the lump sum would be about $237 (including mortality discount). At age 36 the lump sum is $246. So the lump sum will get bigger just because you get older. Very important is the interest discount. At age 30 in the example, 2% interest would produce a $467 lump sum. And at 6% $122. The bigger the rate, the smaller the lump sum because interest helps an amount now grow bigger in the future. To complicate things, since 2008 the IRS bases lump sums on 3 different interest rates. The monthy annuity payments made within 5 years of the lump sum date use the 1st rate, past 5 and within 20 years use the 2nd rate, and past that use the 3rd rate. Since you are age 30, all of your monthly annuity payments would be made after 20 years, so that makes it simple since we'll only have to look at the 3rd rate. When you reach age 45 the 2nd rate will kick in. Here is the table of interest rates published by the IRS: http://www.irs.gov/Retirement-Plans/Minimum-Present-Value-Segment-Rates You'll find your rates above on the 2013 line for Aug-12. That means your lump sum is being made in 2013 and it is being based on the month August 2012. Most likely your plan will use the same rates for its entire plan year. But what is your plan year? If it is the calendar year, then you would have a 5 month lookback for the rates. But if is a September to August plan year with a 1 month lookback, the rates would have changed between August and September. Your August lump sum would be based on 4.52%, your September on would be based on 5.58% (see the All line for Aug-13). For comparison, a 30 year old with a $100 annuity payable at age 65 would have a lump sum value of $3,011 at 4.52%, but a lump sum value of $1,931 at 5.58%. The change in your accrued benefit by month will obviously have some impact on the lump sum value, but not as much as the change in interest rates if there is one. The amount they actually contribute to the plan has nothing to do with the value of the lump sum though.",
"title": ""
},
{
"docid": "188384",
"text": "\"I got $3394.83 The first problem with this is that it is backwards. The NPV (Net Present Value) of three future payments of $997 has to be less than the nominal value. The nominal value is simple: $2991. First step, convert the 8% annual return from the stock market to a monthly return. Everyone else assumed that the 8% is a monthly return, but that is clearly absurd. The correct way to do this would be to solve for m in But we often approximate this by dividing 8% by 12, which would be .67%. Either way, you divide each payment by the number of months of compounding. Sum those up using m equal to about .64% (I left the calculated value in memory and used that rather than the rounded value) and you get about $2952.92 which is smaller than $2991. Obviously $2952.92 is much larger than $2495 and you should not do this. If the three payments were $842.39 instead, then it would about break even. Note that this neglects risk. In a three month period, the stock market is as likely to fall short of an annualized 8% return as to beat it. This would make more sense if your alternative was to pay off some of your mortgage immediately and take the payments or yp pay a lump sum now and increase future mortgage payments. Then your return would be safer. Someone noted in a comment that we would normally base the NPV on the interest rate of the payments. That's for calculating the NPV to the one making the loan. Here, we want to calculate the NPV for the borrower. So the question is what the borrower would do with the money if making payments and not the lump sum. The question assumes that the borrower would invest in the stock market, which is a risky option and not normally advisable. I suggest a mortgage based alternative. If the borrower is going to stuff the money under the mattress until needed, then the answer is simple. The nominal value of $2991 is also the NPV, as mattresses don't pay interest. Similarly, many banks don't pay interest on checking these days. So for someone facing a real decision like this, I'd almost always recommend paying the lump sum and getting it over with. Even if the payments are \"\"same as cash\"\" with no premium charged.\"",
"title": ""
},
{
"docid": "407726",
"text": "\"An annuity is a product. In simple terms, you hand over a lump sum of cash and receive an agreed annual income until you die. The underlying investment required to reach that income level is not your concern, it's the provider's worry. So there is a huge mount of security to the retiree in having an annuity. It is worth pointing out that with simple annuities where one gives a lump sum of money to (typically) an insurance company, the annuity payments cease upon the death of the annuitant. If any part of the lump sum is still left, that money belongs to the company, not to the heirs of the deceased. Fancier versions of annuities cover the spouse of the annuitant as well (joint and survivor annuity) or guarantee a certain number of payments (e.g. 10-year certain) regardless of when the annuitant dies (payments for the remaining certain term go to the residual beneficiary) etc. How much of an annuity payment the company offers for a fixed lump sum of £X depends on what type of annuity is chosen; usually simple annuities give the maximum bang for the buck. Also, different companies may offer slightly different rates. So, why should one choose to buy an annuity instead of keeping the lump sum in a bank or in fixed deposits (CDs in US parlance), or invested in the stock market or the bond market, etc., and making periodic withdrawals from these assets at a \"\"safe rate of withdrawal\"\"? Safe rates of withdrawal are often touted as 4% per annum in the US, though there are newer studies saying that a smaller rate should be used. Well, safe rates of withdrawal are designed to ensure that the retiree does not use up all the money and is left destitute just when medical bills and other costs are likely to be peaking. Indeed, if all the money were kept in a sock at home (no growth at all), a 4% per annum withdrawal rate will last the retiree for 25 years. With some growth of the lump sum in an investment, somewhat larger withdrawals might be taken in good years, but that 4% is needed even when the investments have declined in value because of economic conditions beyond one's control. So, there are good things and bad things that can happen if one chooses to not buy an annuity. On the other hand, with an annuity, the payments will continue till death and so the retiree feels safer, as Chris mentioned. There is also the serenity in not having to worry how the investments are doing; that's the company's business. A down side, of course, is that the payments are fixed and if inflation is raging, the retiree still gets the same amount. If extra cash is needed one year for unavoidable expenses, the annuity will not provide it, whereas the lump sum (whether kept in a sock or invested) can be drawn on for the extra expense. Another down side is that any money remaining is gone, with nothing left for the heirs. On the plus side, the annuity payments are usually larger than those that the retiree will get via the safe rate of withdrawal method from the lump sum. This is because the insurance company is applying the laws of large numbers: many annuitants will not survive past their life expectancy, and their leftover monies are pure profit to the insurance company, often more than enough (when invested properly by the company) to pay those old codgers who continue to live past their life expectancy. Personally, I wouldn't want to buy an annuity with all my money, but getting an annuity with part of the money is worthwhile. Important: The annuity discussed in this answer is what is sometimes called a single-premium or an immediate annuity. It is purchased at the time of retirement with a single (large) lump sum payment. This is not the kind of annuity that is described in JAGAnalyst's answer which requires payment of (much smaller) premiums over many years. Search this forum for variable annuity to learn about these types of annuities.\"",
"title": ""
},
{
"docid": "487621",
"text": "So my advice for your financial situation depends on your aims. Are you aiming to: - Completely clear your debt - Clear one card to free up more monthly income. - Clear some debt to allow further controlled spending - Clear one card and focus on just using one, having 2nd as emergency. There are other things you may wish to do but you said to pay off some / all of 2 credit card bills. If you want to contact me I can plan this more precisely. Some seem the same but other factors can come into play as well. Differing rates of interest make the options clearer. My first advice would be to call the card companies and see if you can get better rates first. SCENARIO (some figures made up for visual) Credit Card Debts 8,000 8,000 Monthly payment 100 100 APR % 10 10 Ignoring APR this will be 80 months to repay (otherwise 140 months using my example amounts above) £28,000 repaid over 11 years 8 months. Your Suggestion As per your suggestion originally, paying off cards equally will allow smaller debt on both cards. Credit Card Debt 3,000 3,000 Monthly payment 100 100 APR % 10 10 With a 0% APR this would be paid off in 2 years 6 months. Cards are available to get free balance transfers, need to look into this. With the 10% APR this would take 3 years 1 month. £10,000 lump and £7,400 repaid over 3 years 1 month (saving £10,600 and 8 years 7 months) AIM: To clear debt completely. My advice here is to use the £10,000 lump sum to pay off one credit card, the remaining £2,000 can then come off the other card. This will free up your outgoings (was 2 x £100) by £100. But then use this £100 to pay off the card, this will result in the following: Credit Card Debt 6,000 Monthly payment 200 APR % 10 With a 0% APR this would be paid off in 2 years 6 months. Cards are available to get free balance transfers, need to look into this. With 10% APR this would take roughly 3 years 1 month. £10,000 lump and £7,400 repaid over 3 years 1 month (saving £10,600 and 8 years 7 months). This option is the same as above, but you have the options on the odd tight month to reduce payments to £100. This also will allow the 2nd card to be used interest free for an emergency purchase (to be paid off without any interest charge) If rates are different, pay of the one with the higher APR AIM: Clear one card to free up more monthly income. AIM: Clear one card and focus on just using one, having 2nd as emergency. Same as above, but don’t increase to £200, leave monthly payment at £100. Credit Card Debt 6,000 Monthly payment 100 APR % 10 With a 0% APR this would be paid off in 5 years. With the 10% APR this would take 88 months (7 years 4 months) £10,000 lump and £8,800 repaid over 7 years and 4 months (saving £9,200 and 4 years 4 months). This also allows for some extra spending (even racking back up the debt – although not advised) AIM: Clear some debt to allow further controlled spending As above apart from this will allow you to spend to get back up to full £16,000 debt. NOTE My figures are theoretical, paying off £500 (£250x2) a month instead of the £100 (10%APR) would take: Lump sum 10,000, remaining 6,000 – 14 months (£17,000 paid) Lump sum 5,000, remaining 2 x 5,500 – 26 months (£18,000 paid) Lump Sum 0, remaining 2 x 8,000 – 40 months (£20,000 paid) Now I have finished waffling, I hope you have an idea on what you are aiming to achieve and a better idea of what to do when you receive the income Stephen.",
"title": ""
},
{
"docid": "323238",
"text": "Have her pay something like a friendly monthly rent. This should be less than half of the monthly mortgage cost, since you are assuming the risk (and benefits) of a mortgage and closer to the rent of similar places near you. For when you get married and she is to have half the apartment, have a pre-agreed way to calculate a lump-sum that she needs to provide to match your own contributions up to that time, as if you two had equal contributions from the beginning. The financially precise way to do it would be to have her pay more than the mere sum of the amount (since she will be providing the amount at a later time than you), but I would be generous and skip this in your place if the difference is not too big. If you break up, she will have payed what would be a fair amount of rent, as if you two were renting, so, in this sense, it is fair that she would not have a claim on the apartment. In case that you two would like that she keeps the apartment, you can just sell it to her, having her pay this same amount as above and assume responsibility for the rest of the mortgage.",
"title": ""
},
{
"docid": "432280",
"text": "\"This is a bit pornographic, isn't it, in that we're looking at something we'd like to do (namely, \"\"win the big lottery!\"\") but probably won't ever have this happen to us. :) Anyway. Ignoring the fact that this is kind of a hypothetical question... Gotta go with The Straight Dope on this one, when deciding whether to take an annuity or a lump sum: What assumed interest rate is underlying the calculations? Do you think you can earn significantly more than that rate on your own? If so, take the lump sum cash value. If not, go with the annuity. What are your financial needs, both immediate and over the next twenty years? Do you need a steady flow of income? If you take the lump sum and invest it poorly or lose it, how much will it hurt you? If you give up your job to enjoy your wealth, what will happen if you're still alive when the annuity payments stop? You don't want to blow it all in a spree and then find yourself in poverty in your old age. What happens if you die before the annuity has been fully paid? As noted, there's the question of whether to ask in advance for an annuity - the tax treatment alone could overwhelm any other considerations.\"",
"title": ""
},
{
"docid": "8601",
"text": "Setting aside for the moment the very relevant issue of whether you need the full amount quickly, I'll just tackle comparing which option gives you to maximum amount of money (in terms of real dollars). The trick is, unless you think inflation will suddenly reverse itself or stop entirely (not likely), $50K today is worth a LOT more than $50K in 20 years. If you don't believe me, consider that just 30 years ago the average price for a mid-level new car was around $3k. When you grandfather says he got a burger for a nickel, he isn't talking about 2010 dollars. So, how do you account for this? Well, the way financial people and project managers do it to estimate how much to pay today for $1 at some point in the future is through a net present value (NPV) calculation. You can find a calculator here. In your question, you gave some numbers for the payout, but not the lump sum prize amount. Going solely on what you have provided, I calculate that you should take the lump sum if it is greater than $766,189.96 which is the net present value of 20 years of $50K Payments assuming 3% annual inflation, which is fairly a fairly reasonable number given history. However, if you think the out-of-control Gov't spending is going to send inflation through the roof (possible, but not a given), then you almost certainly would want the lump sum. I suppose in that scenario you might want the lump sum anyway because if the Govt starts filching on their obligations, doing it to a small number of lottery winners might be politically more popular than cutting other programs that affect a large number of voters.",
"title": ""
},
{
"docid": "559745",
"text": "\"@fredsbend, Hope this helps! \"\"I understand that a reverse mortgage can be paid out in two ways: A lump sum and monthly payments. I figure that if you take the lump sum, eventually, the bank wants you to start paying it back.\"\" Answer: Actually, there are 3 payout options, or 4 if you consider a combination payout as another one. There's a lump sum, a line of credit, or the monthly payout, or a combination. \"\"I figure that if you take the monthly payments, eventually, the bank stops paying out and wants you to pay it back. In both situations, interest accrues and this is how the bank makes money off of the deal\"\". Answer: The only time the monthly payments would stop would be if the borrower defaults on the lenders' terms or they no longer live at home. You are right though, and interest does accrue on whichever payment is decided on. I'm not sure how the lender makes money, probably by the interest, but I know borrowers are protected against high rates and owing more than your house. Here's an article I found that goes over the protections more in detail: https://www.americanadvisorsgroup.com/news/6-consumer-protections-reverse-mortgage-loan-borrowers. \"\"But what determines when you have to begin paying back the reverse mortgage? Some sources online seem to say that it's based only on if you die or would like to sell/move. That can't be right in all situations, because you could end up with a massive debt on a property more than its value.\"\" Answer: There are a lot of protections or regulations in place to protect anyone who takes out a reverse mortgage. One being, you can't owe MORE than your house is valued at during the time of repayment, a reverse mortgage is a non-recourse loan. In the instance that your house is less than you owe, you either sell the home and the proceeds are used to pay the loan and you keep the rest OR if you owe more than the house proceeds of the home go to the lender. Either way, you're not left paying for a \"\"mortgage\"\" without the house. In the case the parent, grandparent passes, then the heirs would have a choice of either paying back the reverse mortgage in payments, OR they can sell the house, heirs are protected during this as well to make sure they're not left with major debt in case of anything. Is there a formula to figure out when the bank stops the monthly payments and then wants it back? **Answer:**The amount becomes due if loan terms are not met, but the lender will discuss the options if it comes to that. Is there a different formula for when the lump sum would have to be paid back?\"\" Answer: Each payout option has the same terms and the same pay back terms. As long as terms are met, the lender can't ask for early repayment.\"",
"title": ""
},
{
"docid": "391583",
"text": "Retirement calculation, in general, should be based on the amount of money needed per year/month and the expected life expectancy. Life expectancy, if calculated to 90 years (let's say) indicates that post retirement age (60 yrs.) your accumulated/invested money should generate adequate income to cover your expenses till 90 years. The problem in general is not how long you shall live but what would be your expected spending from retirement to end of life expectancy. The idea is at the minimum your investments should generate income that is inflation adjusted. One way to do this is to consider your monthly expense now i.e. the expense that is absolute minimum for carrying on (food, electricity, water, medicines, household consumables, car petrol, insurance, servicing, entertainment, newspaper etc.) this does not contain the amortizable liabilities (home loan, child's education, other debts). It is better to take this amount per family rather than per person and yearly rather than monthly (as we tend to miss a lot of yearly expenses). This amount that you need today will increase at a Compounded Annual Growth Rate (CAGR) of the average inflation. For example, if today you spend 100 per year in 7 years you will need to spend appx. 200 at 10% inflation. Now, your investments will not increase post your retirement, so your current investment needs to do two things (1) give you your yearly requirement (2) grow by a fixed amount so that next year it can give you CAGR adjusted returns. In general, this kind of investment grows by high net amounts initially and slowly the growth decrease. The above can be calculated by Net Present value (NPV) formulae (http://en.wikipedia.org/wiki/Net_present_value). The key is to remember that the money that is invested when you retire should be able to give you inflation adjusted returns to cover your yearly expenses. How much money you need depends on your life style/expectation and how much return is received depends on the instruments that you invest on. As for your question above on the difference between the age of you and your spouse, it better to go with the consolidated family requirement and get an idea of how much investment is necessary and provision the same as soon as possible from your as well as your spouse's income. Hope this helps.- thanks",
"title": ""
},
{
"docid": "180071",
"text": "\"There are two options (according to Wells Fargo). You can either apply for a Business/Commercial Equity Loan or a Line of Credit. A loan is what it sounds like - they give you a lump sum of money for you to use and you have to pay it in monthly installments. A line of credit is like a credit card, you have money that you can borrow (up to a certain amount) and you have to make monthly payments. The process can differ for different business, they probably look at what your real estate is worth, how much money you are generating from it, etc. I am not recommending or endorsing Wells Fargo, other major banks offer the same types of products, Wells Fargo just happened to appear first when I searched for \"\"business line of credit\"\".\"",
"title": ""
},
{
"docid": "539112",
"text": "\"The specific \"\"State Pension\"\" plan you have linked to is provided by the government of the U.K. to workers resident there. More generally speaking, many countries provide some kind of basic worker's pension (or \"\"social security\"\") to residents. In the United States, it is called (surprise!) \"\"Social Security\"\", and in Canada most of us call ours \"\"Canada Pension Plan\"\". Such pensions are typically funded by payroll deductions distinct & separate from income tax deducted at source. You can learn about the variety of social security programs around the world courtesy of the U.S. Social Security Administration's own survey. What those and many other government or state pensions have in common, and the term or concept that I think you are looking for, is that they are typically defined benefit type of plans. A defined benefit or DB plan is where there is a promised (or \"\"defined\"\") benefit, i.e. a set lump sum amount (such as with a \"\"cash balance\"\" type of DB plan) or income per year in retirement (more typical). (Note: Defined benefit plans are not restricted to be offered by governments only. Many companies also offer DB plans to their employees, but DB plans in the private sector are becoming more rare due to the funding risk inherent in making such a long-term promise to employees.) Whereas a defined contribution or DC plan is one where employee and/or employer put money into a retirement account, the balance of which is invested in a selection of funds. Then, at retirement the resulting lump sum amount or annual income amounts (if the resulting balance is annuitized) are based on the performance of the investments selected. That is, with a DC plan, there is no promise of you getting either a set lump sum amount or a set amount of annual income at retirement! The promise was up front, on how much money they would contribute. So, the contributions are defined (often according to a matching contribution scheme), yet the resulting benefit itself is not defined (i.e. promised.) Summary: DB plans promise you the money (the benefit) you'll get at retirement. DC plans only promise you the money (the contributions) you get now.\"",
"title": ""
},
{
"docid": "217222",
"text": "The equation is the same one used for mortgage amortization. You first want to calculate the PV (present value) for a stream of $50K payments over 20 years at a10% rate. Then that value is the FV (future value) that you want to save for, and you are looking to solve the payment stream needed to create that future value. Good luck achieving the 10% return, and in knowing your mortality down to the exact year. Unless this is a homework assignment, which need not reflect real life. Edit - as indicated above, the first step is to get that value in 20 years: The image is the user-friendly entry screen for the PV calculation. It walks you though the need to enter rate as per period, therefore I enter .1/12 as the rate. The payment you desire is $50K/yr, and since it's a payment, it's a negative number. The equation in excel that results is: =PV(0.1/12,240,-50000/12,0) and the sum calculated is $431,769 Next you wish to know the payments to make to arrive at this number: In this case, you start at zero PV with a known FV calculated above, and known rate. This solves for the payment needed to get this number, $568.59 The excel equation is: =PMT(0.1/12,240,0,431769) Most people have access to excel or a public domain spreadsheet application (e.g. Openoffice). If you are often needing to perform such calculations, a business finance calculator is recommended. TI used to make a model BA-35 finance calculator, no longer in production, still on eBay, used. One more update- these equations whether in excel or a calculator are geared toward per period interest, i.e. when you state 10%, they assume a monthly 10/12%. With that said, you required a 20 year deposit period and 20 year withdrawal period. We know you wish to take out $4166.67 per month. The equation to calculate deposit required becomes - 4166.67/(1.00833333)^240= 568.59 HA! Exact same answer, far less work. To be clear, this works only because you required 240 deposits to produce 240 withdrawals in the future.",
"title": ""
},
{
"docid": "17633",
"text": "There can be Federal estate tax as well as State estate tax due on an estate, but it is not of direct concern to you. Estate taxes are paid by the estate of the decedent, not by the beneficiaries, and so you do not owe any estate tax. As a matter of fact, most estates in the US do not pay Federal estate tax at all because only the amount that exceeds the Federal exemption ($5.5M) is taxable, and most estates are smaller. State estate taxes might be a different matter because while many states exempt exactly what the Federal Government does, others exempt different (usually smaller) amounts. But in any case, estate taxes are not of concern to you except insofar as what you inherit is reduced because the estate had to pay estate tax before distributing the inheritances. As JoeTaxpayer's answer says more succinctly, what you inherit is net of estate tax, if any. What you receive as an inheritance is not taxable income to you either. If you receive stock shares or other property, your basis is the value of the property when you inherit it. Thus, if you sell at a later time, you will have to pay taxes only on the increase in the value of the property from the time you inherit it. The increase in value from the time the decedent acquired the property till the date of death is not taxable income to you. Exceptions to all these favorable rules to you is the treatment of Traditional IRAs, 401ks, pension plans etc that you inherit that contain money on which the decedent never paid income tax. Distributions from such inherited accounts are (mostly) taxable income to you; any part of post-tax money such as nondeductible contributions to Traditional IRAs that is included in the distribution is tax-free. Annuities present another source of complications. For annuities within IRAs, even the IRS throws up its hands at explaining things to mere mortals who are foolhardy enough to delve into Pub 950, saying in effect, talk to your tax advisor. For other annuities, questions arise such as is this a tax-deferred annuity and whether it was purchased with pre-tax money or with post-tax money, etc. One thing that you should check out is whether it is beneficial to take a lump sum distribution or just collect the money as it is distributed in monthly, quarterly, semi-annual, or annual payments. Annuities in particular have heavy surrender charges if they are terminated early and the money taken as a lump sum instead of over time as the insurance company issuing the annuity had planned on happening. So, taking a lump sum would mean more income tax immediately due not just on the lump sum but because the increase in AGI might reduce deductions for medical expenses as well as reduce the overall amount of itemized deductions that can be claimed, increase taxability of social security benefits, etc. You say that you have these angles sussed out, and so I will merely re-iterate Beware the surrender charges.",
"title": ""
},
{
"docid": "197576",
"text": "First of all depending on the type of IRA you may not have to pay taxes on withdrawals in the US at all. If you are withdrawing your principle from a Roth IRA then you don't owe taxes. Only when you withdraw the gains do you pay taxes on it. You have two options for withdrawals: Lump Sum Withdrawal: If you take a lump sum withdrawal you will owe taxes to the US (30% for non-resident aliens of the US), and according to DTAA; Article 23, you will file your taxes with India declaring your IRA or 401(k) withdrawal proceeds and claim credit on the taxes you paid to the US. Monthly Pension Withdrawal: You can also receive monthly pension payments and you will only be taxed in the country in which you are a resident of. This is according to DTAA, Article 20. You would then have to submit necessary documentation to your payer in the US so that they do not withhold any taxes in the US. Just as a side note it might be just better to keep the money where it is and let it grow or roll it over to a Roth IRA if you are currently in a lower tax bracket for maximum savings of your principle. Here is a link with more detailed information of what I provided you: http://articles.economictimes.indiatimes.com/2012-01-25/news/30663129_1_taxable-income-nri-401k-plan",
"title": ""
},
{
"docid": "465283",
"text": "After some thought, I follow Dave Ramsey's advice because it's simple and I can do the math in my head - no online calculator needed. :) You need Life Insurance if someone depends on your income. You can replace your income with a single lump sum of 8-10 times your current income where those who need your income, can get roughly your salary each year from the life insurance proceeds.",
"title": ""
},
{
"docid": "34538",
"text": "\"Some details in case you are interested: Being a defined benefit kind of pension plan, the formula for your Social Security benefits isn't tied directly to FICA contributions, and I'm not aware of any calculator that performs an ROI based on FICA contributions. Rather, how much you'll get in retirement is based on your average indexed monthly earnings. Here's some information on the Social Security calculation from the Social Security Administration - Primary Insurance Amount (PIA): For an individual who first becomes eligible for old-age insurance benefits or disability insurance benefits in 2013, or who dies in 2013 before becoming eligible for benefits, his/her PIA will be the sum of: (a) 90 percent of the first $791 of his/her average indexed monthly earnings, plus (b) 32 percent of his/her average indexed monthly earnings over $791 and through $4,768, plus (c) 15 percent of his/her average indexed monthly earnings over $4,768. Here's an example. Of course, to calculate a benefit in the future, you'll need to calculate projected average indexed monthly earnings; more details here. You'll also need to make assumptions about what those bend points might be in the future. The average wage indexing values for calculating the AIME are available from the Social Security Administration's site, but future indexing values will also need to be projected based on an assumption about their inflation. You'll also need to project the Contribution and Benefit Base which limits the earnings used to calculate contributions and benefits. Also, the PIA calculation assumes benefits are taken at the normal retirement age. Calculating an early or late retirement factor is required to adjust benefits for another age. Then, whatever benefits you get will increase each year, because the benefit is increased based on annual changes in the cost of living. Performing the series of calculations by hand isn't my idea of fun, but implementing it as a spreadsheet (or a web page) and adding in some \"\"ROI based on FICA contributions\"\" calculations might be an interesting exercise if you are so inclined? For completeness sake, I'll mention that the SSA also provides source code for a Social Security Benefit Calculator.\"",
"title": ""
},
{
"docid": "320362",
"text": "\"You'd need to talk with an attorney familiar with Social Security, or an appropriately qualified SSA representative to be sure - but all signs point to the idea that unfortunately Social Security does not work the way your father was told it would. And if he doesn't file to receive benefits the reality is actually much worse than \"\"throwing away free money\"\"! However, this is not due to a complete misunderstanding of the system! Social Security does work the way he thinks in some instances, just that the rules don't apply to his exact situation! First of all, retroactive benefits come in a few forms: File and suspend to get a lump only if you really need it - BEFORE the age of 70 only! In this method you apply for retirement, but you tell the SSA to suspend/delay your benefits. You are entitled to full lump sum of the payments you deferred...but at a cost of getting lower monthly benefits permanently (and that also lowers spousal and dependent children's benefits, too - if those could apply to your dad). But note that at the age of 70, Social Security will stop deferring the payments and start paying you the full maximum retirement benefit monthly, with no lump sum. This is a kind of emergency insurance policy for those who want to try to defer retirement benefits, but who want the opportunity to cash out and get the money they would have been getting \"\"just in case\"\". You can get up to 6 months of retroactive benefits, such as if you wait past your exact retirement age to apply for benefits. But no more: \"\"we cannot pay retroactive benefits for any month before you reached full retirement age or more than 6 months in the past\"\". As for after-death benefits, an estate can only get benefits that were already due to be paid, which generally means a person died and did not get their benefits for that month, so SSA can re-issue a check to the estate following these rules. But as a person cannot be due a lump sum payment after age 70 (for more than 6 months at most), the estate will only be able to get at most 1-6 months of payments (and 6 months is doubtful - you'll need to ask a lawyer if that much would even be possible). If your father was below 70 and wanted to file-and-suspend, the question of lump on death would be more complex and I don't know that answer - but once you are past 70 this doesn't matter any more as you aren't due a lump anymore. Given the above, we've established pretty clearly that if you don't claim your benefits within 6 months after age 70, any months of payment you would have gotten are just forfeited to the system. But if you claim the benefits and stick them in the bank, can they be taken? Well, if a lawsuit is really a worry, then yes these accumulated funds can required to pay a debt - but this potential for loss can be protected against without forfeiting the benefits entirely! This is not very common, but if your father doesn't need the money now he may be able to deposit some of the money into a special partially-lawsuit protected format of the Roth IRA (which has no age limits) as detailed here. If he never gets sued, that's OK - it's still his money! If he passes away, the value goes to his estate and does not disappear. And he doesn't forfeit any of his earned retirement benefits. Finally, I would like to share one last thing with you and your father. These benefits aren't free - he has been paying a portion of his paycheck for decades into Social Security, and now he is eligible for the maximum amount of benefits per month that he will qualify for - and if he wants to keep working he loses no benefit and the amount could potentially even go up. That's up to him. But not filing for benefits now will mean that all this money he's been paying in for decades will just be lost - they'll basically just be a tax he's paid out to other retirees. His estate (which means you kids) won't get any of it, either. That'd just be a waste for everyone involved. If you have continued doubts or questions, I wouldn't hesitate to consult a specialist lawyer or talk with the SSA directly to make sure this is all correct. It's his money, and he has earned his benefits for many years. I very much hope he gets to enjoy as much of them as he can!\"",
"title": ""
},
{
"docid": "308010",
"text": "As mentioned in other answers the interest you make is negligible and the calculations would depend on the bank. In saying that the general trend is calculate daily, pay monthly. A typical scenario would be that every night at midnight the interest for your account at that point in time is calculated. This occurs every midnight and at the end of the month the sum of those calculations will be added to your account. You could have had several significant transactions pass through your account in one day although if the interest is calculated at a specific point in time some transactions may not contribute to any interest. These calculations are worth thinking about, even in circumstances of negligible returns, as it could assist when considering combining credit cards with home loan offset accounts so it is not a complete waste of time to understand how interest is calculated. The more you know ;)",
"title": ""
},
{
"docid": "181732",
"text": "\"You can use the 6900 to make an investment. Or to buy something. That's why people keep reminding you that you could make interest. Because most people think of either 7200 now or paying the same 7200 over time. So you could just be storing the 7200 under the mattress until you pay it out. Obviously in that case, inflation doesn't matter (\"\"is not applicable\"\"). You've given up the use of the 7200 from the beginning. Think of it instead as 7200 now and twenty-three payments of 300 each. So 14,100 total. Then you can spend 6900 on something else at the beginning or spend 300 a month on other things. The difference between spending 6900 now and 300 in each of twenty-three months would be measured in inflation. Of course, this requires you to have both 7200 now and an income stream producing at least 300 a month. Another way of doing things is to take 6900 and invest it. Each month you remove 300 and use it to make a payment. We're now back to just one 7200, plus the interest over time. I would argue that this is still an inflation advantage. It's just that instead of spending the money, you invested it. And that of course is your prerogative. The point being that you would not have that opportunity if you paid up front. Now to calculate the difference in monthly payments of 300 euro using the above webpage what should I do? As already said, you would have to calculate twenty-three values and then sum them with the 300 you pay up front in the monthly. There are other ways to calculate it, if you are not using that particular tool. For example, there are formulas to calculate the net present value of an annuity. E.g. see Investopedia. Where: P = the present value of an annuity stream PMT = the dollar amount of each annuity payment r = the inflation rate n = the number of periods in which payments will be made Investopedia talks about interest rates, but you can put inflation there for this purpose. In that case, r might better be called the \"\"discount rate\"\". PMT is 300. r is whatever estimate you are using for inflation. E.g. .003 per period. n is 23. Note that the monthly inflation rate is smaller than the annual rate. So .003 is about 3.66% annually. 3.04% annually is more like .0025 a month. I found calculators for this with search terms \"\"present value of annuity calculator\"\". Some of the calculators will take the annual rate (3.66%) and number of periods per year as input. Or the calculator may take a monthly rate as a percentage (.3%) rather than as a decimal (.003). So be careful of the inputs. This gives me a net present value (NPV) of 6,657.69 for the 23 payments of 300, assuming .3%. Or 6957.69 is the NPV of the monthly payments and 7200 is the NPV of the 7200 up front. Obviously if you can pay less than 6957.69 up front rather than 7200, then it makes more sense to pay up front. Even without a discount though, it still may make more sense to pay up front. How much those intangibles are worth is up to you.\"",
"title": ""
},
{
"docid": "131451",
"text": "\"For example, for my employer I received a signing bonus, and a \"\"relocation lump sum\"\" separate from that signing bonus. The relocation lump sum is taxed and will appear as income on my W-2, and I can spend it on anything I want. That said, should the relocation lump sum count towards the entry quoted above in Form 3903, or would it be considered the same as any other bonus; thus allowing me to take a full deduction for all of my deductible travel expenses? The signing bonus and relocation lump sum will appear as regular income on your W-2. You can think of the relocation bonus as something to cover the pain and suffering the cost of moving, without needing to send in receipts. Lets assume that you meet the distance and time tests, so there is potential to save money on your taxes. Lets also put your actual moving expenses as $2500. If you have valid moving expenses the IRS will allow you to use them to reduce your AGI. So now you can reduce your AGI by the $2500. Enter the total amount your employer paid you for the expenses listed on lines 1 and 2 that is not included in box 1 of your Form W-2 (wages). This amount should be shown in box 12 of your Form W-2 with code P. My question is: what exact payments from your employer should be entered here? I realize that you can just write the number you get in box 12 with code P on your W-2, but I'm curious how they come up with this number. In some cases the company will reimburse you your moving expenses up to a maximum of $x. For example a maximum of $1000 That means you submit receipts for those expenses and they give you a check or add it to your next paycheck. The check will either be for the amount on your receipts or the maximum amount, whichever is smaller. In this situation with actual expenses of $2500 and a reimbursement of $1000 you can reduce your AGI by $1500.\"",
"title": ""
},
{
"docid": "270022",
"text": "As I see it the two main considerations are: Total amount of money received, for which the key variable is life expectancy. 41000 * 0.8 = 32800, so at £86 / week she would only be better off with the lump sum if she expected to live for less than ~7.3 years. Obviously none of us have a crystal ball, but you could make some assessment based on her current health, risk factors etc. to see whether that seemed feasible. Also you do have to bear in mind that the value of £86 in 7 years' time will be less than it is now - but I guess the £86 would be inflation adjusted? Her need for income (versus capital). If she takes a lump sum and invests it in a house, that is great but doesn't provide any income at all. If she has sufficient income from other sources (and forecasts this other income to continue until her death) then the lump sum might be more attractive, but if not then she would need to be sure that she wasn't tying up the money unnecessarily. Another option here would be using the lump sum to buy an annuity, and it might be wroth exploring this, but I doubt whether the rates would be good enough to beat the £86 / week she is being offered as an alternative. Another (lesser?) consideration is her future entitlement to state-funded care if needed in her later years. If you have assets above a certain amount you are expected to fund your own care, in which case having an expensive house might actually be more of a liability than a help.",
"title": ""
},
{
"docid": "30935",
"text": "\"No, I do not. The advice is to take advice :-) but it is not required. Several \"\"low cost\"\" SIPPs allow an \"\"Execution Only\"\" transfer from some pensions (generally not occupational or defined benefits schemes [where transfers are generally a bad idea anyway] but FAVCs such as mine are ok). Best Invest is one such, and the fees are indeed relatively low. As far as anyone knows, the government's plans for changes to rules on using pension funds would still apply even once I've transferred my pension pot and begun to withdraw funds (provided I don't commit myself to an annuity or other irrevocable investment). I am not a financial adviser, nor employed or otherwise connected with Best Invest, and I'm not endorsing their SIPP schemes, just giving them as an example of what can be done. [Added after I carried out my plan] I found the process very straightforward; I needed to apply for a pension fund with my new provider and fill in a transfer form, which set up the scheme and transferred the funds with no expense required. Once the money arrived in my pension account I filled in another form to take the lump sum and set up regular withdrawals from the fund. I had my lump sum within a couple of months of initiating the transfer. I'm very happy I did not take independent advice because it would have been very poor value for money. During my researches I was approached eagerly by one firm promising to get me my money quick and claiming to be an independent financial advisor. Luckily I mistrusted the service they offered.\"",
"title": ""
},
{
"docid": "173213",
"text": "\"Looking at some large lotto games out there, it seems that the lump sum (cash) option comes in at anywhere from about 50 to 70 percent of the jackpot amount (sum of annual payouts, typically over 20 to 30 years). I'm a fan of the phrase \"\"money today is better than money tomorrow.\"\" There's no telling how laws will change, taxes will change, if inflation will skyrocket, if you'll die early, if you or a family member will encounter a life-changing event, etc. By taking the lump sum option you trade a percentage of the winnings for the risk of the future unknowns. How much are those unknowns worth to you? The tax implications are something else to consider. In your example of a \"\"small\"\" jackpot with $50,000 annual payouts, it's likely that you could still avoid the highest tax bracket each year, whereas taking the lump sum would be taxed at the highest rate (35% of the amount above $373k, for a single filer in 2010). However, this might not make much of a difference for large jackpots with higher annual payouts. With the lump sum option, you also have a greater potential of investment returns (and losses) since you can put all the money to work for you right away. It also allows you to purchase larger assets sooner, if that's something that interests you. In the end, I'd say the reduced risk and the higher return potential of the lump sum option is well worth the reduced payout. I'd also suggest not playing the lottery :)\"",
"title": ""
},
{
"docid": "488638",
"text": "\"Really this is no different from any kind of large lump sum and having a mortgage. There are probably many questions and answers on this subject. It really doesn't matter that the proceeds were the result of a sale, an inheritance would not change the answer. I think it is important to note that the proceeds will not eliminate the house 2 mortgage. A high level choice of investment one makes is between equity (such as stock) and debt investments (such as bonds and mortgages). You are in a unique case of being able to invest in your own mortgage with no investment fee. This may tip the scales in favor of paying down the mortgage. It is difficult to answer in your specific case as we don't know the rest of your finances. Do you have a sizable 401K that is heavily invested in stocks? Do you have the need for a college fund? Do you have an emergency fund? Do you have a desire to own several homes generating income property? If it was me I'd do the following in order, skipping steps I may have already completed: I've heard that the bank may agree to a \"\"one time adjustment\"\" to lower the payments on Mortgage #2 because of paying a very large payment. Is this something that really happens? I really kind of hate this attitude. Your goal is to get rid of the mortgage in a timely manner. Doing such makes paying for kids college a snap, reduces the income one might need in retirement, basically eliminates the need for life insurance, and gives one a whole lot of money to have fun with.\"",
"title": ""
},
{
"docid": "497281",
"text": "There are a number of scholarly articles on the subject including a number at the end of the Vanguard article you reference. However, unfortunately like much of financial research you can't look at the articles without paying quite a bit. It is not easy to make a generic comparison between lump-sum and dollar cost averaging because there are many ways to do dollar cost averaging. How long do you average over? Do you evenly average or exponentially put the money to work? The easiest way to think about this problem though is does the extra compounding from investing more of the money immediately outweigh the chance that you may have invested all the money when the market is overvalued. Since the market is usually near the correct value investing in lump sum will usually win out as the Vanguard article suggests. As a side note, while using DCA on a large one time sum of money is generally not optimal, if you have a consistent salary DCA by frequently investing a portion of your salary has been frequently shown to be a very good idea of long periods over saving up a bunch of money and investing it all at once. In this case you get the compounding advantage of investing early and you avoid investing a large chunk of money when the market is overvalued.",
"title": ""
},
{
"docid": "68872",
"text": "\"Note - this is a complicated topic. I've read the rules multiple times and I'm still not sure I understand them perfectly. So please take this with a pinch of salt and read the rules for yourself. The time(s) at which a test is done against the LTA are known as a \"\"Benefit Crystallization Event\"\" (BCE). There are 13 of these (!) - they're numbered 1-9 with the addition of some extras numbered 5A-D. However, the most important ones for those with defined contribution pensions are: Broadly, the idea is that a BCE occurs when you start taking money out of your pension, and when you reach age 75. Each time one happens, the amount you are taking out (\"\"crystallizing\"\") gets compared against the LTA and a certain percentage of your LTA gets designated as being used. Crystallising doesn't necessarily mean you actually receive the money immediately, just that some of your money is switched into a mode where you can start receiving it in different ways. The rules are designed to avoid double counting, so broadly anything that was taken off your LTA won't be taken off a second time. The cumulative use of your LTA is tracked as a percentage rather than an absolute amount, to take account of any changes in the LTA between the different times you crystallise money. For example if you crystallise £100K when the LTA is £1mn, that's 10% of your LTA gone. If later on the LTA has risen to £1.1mn and you take out £110K, that's another 10%. Once you hit 100%, you start paying a LTA charge on any excess. The really simple path here is if you just get an annuity with your entire pot, before hitting age 75 (and you don't make any further pension contributions after). Then only BCE 4 applies: your pension pot, all of which is being used to buy the annuity, is compared with the LTA. After this point your entire pension pot is considered to be crystallized, so no more BCEs will apply - the tests at age 75 only apply if you still have money that you haven't taken out or used to buy an annuity. The annuity payments themselves will be subject to income tax at your normal rate at the time you receive them, i.e. 0%, 20%, 40% or 45% depending on how much other income you have. In reality most people would want to take 25% of their pot as a lump sum at the same time as buying an annuity, given that it's tax-free if you're under the LTA. At this point BCE 6 applies in addition to BCE 4, but again the overall effect of the test is pretty simple, look at the total pension pot (lump sum + cost of annuity), and if it's under the LTA you're fine. Again, at this point no more BCEs will apply as all the money is considered to have been fully distributed. If you only use part of the money for an annuity/lump sum, then only that part of the money is compared against the LTA, and the rest stays in your pension and will be compared later. The 25% limit for a tax-free lump sum applies to the total you are taking out at that point: if you have £200K and are taking out £100K, you can take out £25K as a tax-free lump sum and use £75K for the annuity. The other £100K stays in your pension. Many people see annuity rates as very low and will want to take on more risk (and reward) by using \"\"Drawdown\"\" for at least part of their pension. Essentially, you can designate part of your pension for drawdown, and at that point BCE 1 applies to the money you designate. Once designated, you can start drawing the money out as income, which will be taxed at your normal income tax rate at the time you receive it. Again, you can take 25% as a lump sum at this point which will be subject to BCE 6. There's also an alternative route where you put everything into \"\"flexi-access drawdown\"\" without taking any lump sum immediately, and then as you actually withdraw income, 25% is tax-free and the rest is taxed as income. The overall effect is the same, but it gives you more control over when you get the tax-free bit. However, because with drawdown you can actually leave the money in your pension and growing tax-free, there's a further test against the LTA at age 75 under BCE 5A. To avoid double-counting (\"\"prevention of overlap\"\"), the amount left in the drawdown fund at that point is reduced by whatever was previously tested against BCE 1. So if you put £150K into drawdown initially, and it's grown to £200K by age 75, then another £50K will crystallise under BCE 5A. I think that if you put £150K into drawdown initially and it grows by £50K, but you take that out as income so that only £150K (or less) remains at age 75, then the amount crystallising under BCE 5A is nil. Also, when money is in drawdown, you can choose to use it to buy an annuity. BCE 4 is applied at this point (if before age 75), but as with BCE 5A, this is reduced by anything that was previously crystallised under BCE 1. If you only use some of it to buy an annuity, the reduction is pro-rataed, e.g. if you started out with £150K moved into drawdown, and later it has grown to £200K and you use £100K to buy an annuity, then the reduction is £75K so £25K is considered to have crystallised under BCE 4. Once you reach age 75, as well as any money that's still in drawdown, anything you haven't yet crystallised at all gets tested against the LTA under BCE 5B. Broadly, once you go over the LTA, the charges are simple: There's never any explanation given for these two rates, but I think it's all based on trying to at least cancel out the benefit you got from using your pension, on the assumption that: So with the 25% charge + 20% income tax, if you take out £100, you'll end up with £75 gross income, so £60 net income - just the same as if you'd originally paid 40% tax. (This ignores the effect of investment growth, but if you would have saved the £60 in an ISA, the end result is the same: if you had growth of say 50% over the time the money was in your pension, it'll be the same effect if you had £100 growing to £150 and now received 60% of it, or if you had £60 growing to £90 untaxed in an ISA.) The 55% lump sum charge is in case you are paying 40% tax when you take it out, to make sure that it's not a more attractive option than the 25%+income tax: if you have £100, either you get £45 tax free via a lump sum, or you get £75 gross and hence £45 net. I haven't covered lots of cases here: defined benefit pensions. Roughly, when you start receiving the pension, 20x the initial income from the pension is deemed to crystallise under BCE 2 and any lump sum you receive crystallises under BCE 6. In the former case, you could end up having to pay the LTA charge with money you haven't actually got yet, and you can ask the pension administrator to instead reduce your pension to pay it. However, there are lots of special cases for defined benefit pensions, mostly for historical reasons, so you should make sure you check with your pension administrator about this. if you die before age 75, at which point the LTA test is applied via either BCE 5C/5D, or BCE 7. After paying the LTA charge if any, your dependents or whoever else you leave it to gets the remainder tax-free. transferring overseas (BCE 8). \"\"scheme pensions\"\" under BCE 2 and BCE 3 (I think these are relatively uncommon) some corner cases covered by regulations (BCE 9)\"",
"title": ""
},
{
"docid": "481475",
"text": "I have had pension programs with two companies. The first told you what your benefit would be if you retired at age X with Y years of service. Each year of service got you a percentage of your final years salary. There was a different formula for early retirement, and there was an offset for social security. They were responsible for putting enough money away each year to meet their obligations. Just before I left they did add a new feature. You could get the funds in the account in a lump sum when you left. If you left early you got the money in the account. If you left at retirement age you got the money that was needed to produce the benefit you were promised. Which was based on current interest rates. The second company had a plan where they published the funding formula. You knew with every quarterly statement how much was in your account, and what interest it had earned, and what benefit they estimated you would receive if you stayed until retirement age. This fund felt almost like a defined contribution, because the formula was published. If most people took the lump sum that was the only part that mattered. Both pension plans had a different set of formulas based on marriage status and survivor rules. The interest rates are important because they are used to determine how much money is needed to produce the promised monthly benefit. They are also used to determine how much they need to allocate each year to cover their obligations. If you can't make the math work you need to keep contacting HR. You need to understand how much should be flowing into the account each month.",
"title": ""
},
{
"docid": "232700",
"text": "\"Firstly, you should familiarise yourself with your options for your pension fund. They changed as of 6th April 2015 so it's all quite new. The Government's guidance on it is here. If you haven't already taken a tax-free lump sum from your pension fund, you can take up to 25% totally tax free immediately. That makes getting a house for 40K very accessible. Beyond the 25%, you can take any of it out whenever you want (\"\"flexi-access drawdown\"\" or \"\"lump sum payment\"\", depending on whether you take the 25% out up front or not). That'll be taxed, as if you earned it as income. So if you didn't have any other income, you can take another £10600 without tax this tax year, and then another £10600 or whatever the allowance goes up to next tax year, and so on. Above that you'd have to pay 20% tax until you reach the higher-rate tax threshold at about £40K/year. You say you do have other income so you'll have to take that into account as well when calculating what tax you'd have to pay. If you've reached state pension age that will add some more income, of course. Or, as you suggest, you can buy an annuity. You can do that with some or all of the money, and you can still take the 25% tax-free first. If you do buy an annuity the income from it will all be taxed, but again your personal allowance will apply. Essentially an annuity is the least risky option, particularly if you get one that is uprated with inflation. Uprating with inflation makes the initial income even lower but protects you against cost of living rises as you get older. In exchange for avoiding that risk, you probably lose out on average compared to some more risky options. You might choose to get an annuity large enough to cover your basic needs and take more chances with the rest.\"",
"title": ""
},
{
"docid": "325185",
"text": "We can't know the future, of course, but we know that on average it's better to invest a lump sum. We can look at some periods of recent history to get a sense of the difference between a lump sum 450k investment and maybe say 5 years of 90k. Using S&P 500 return rates, let's say you started investing on Jan 1, 2008: Here, spreading your investing over 5 years earns you an extra $163k. Starting a year later, the same strategy would earn you $327k less than a lump investment: I looked at some other periods, but the story doesn't change from what we already knew; you can reduce risk of losing a big chunk due to a bad year, but it comes at the cost of potential gains. Perhaps you could make a killing by waiting for the next down-turn and buying on the cheap, or maybe you'll just be wasting time and money as the market enjoys sustained growth. I'd go with a lump, trusting the averages; but you're right, another 2008 with no recovery would suck. As for holding $50k back it depends primarily on your monthly budget, many people suggest a 3-8 month liquid emergency fund, I like 6 months. Go with what you're comfortable with.",
"title": ""
}
] |
5a891a6f55429951533612c3
|
What other film, beside the American neo-noir dystopian science fiction action film directed by Alex Proyas was considered a blockbuster in 2004?
|
[
{
"docid": "294634",
"text": "The year 2004 in film involved some significant events. Major releases of sequels took place. It included blockbuster films like \"Shrek 2\", \"Harry Potter and the Prisoner of Azkaban\", \"The Bourne Supremacy\", \"Van Helsing\", \"The Passion of the Christ\", \"\", \"Thunderbirds\", \"Meet the Fockers\", \"Harold and Kumar\", \"The Day After Tomorrow\", \"Anchorman\", \"Saw\", \"\", \"Spider-Man 2\", \"Alien vs. Predator\", \"The Incredibles\", \"Kill Bill Vol. 2\", \"Fahrenheit 9/11\", \"I, Robot\", \"Ocean's Twelve\" and \"\".",
"title": ""
},
{
"docid": "564947",
"text": "I, Robot (stylized as i,robot ) is a 2004 American neo-noir dystopian science fiction action film directed by Alex Proyas. The screenplay by Jeff Vintar and Akiva Goldsman is from a screen story by Vintar, suggested by Isaac Asimov's short-story collection of the same name. The film stars Will Smith, Bridget Moynahan, Bruce Greenwood, James Cromwell, Chi McBride, Alan Tudyk and Shia LaBeouf.",
"title": ""
}
] |
[
{
"docid": "1884712",
"text": "Dark City is a 1998 American-Australian neo-noir science fiction film directed by Alex Proyas. The screenplay was written by Proyas, Lem Dobbs and David S. Goyer. The film stars Rufus Sewell, Kiefer Sutherland, Jennifer Connelly, and William Hurt. Sewell plays John Murdoch, an amnesiac man who finds himself suspected of murder. Murdoch attempts to discover his true identity and clear his name while on the run from the police and a mysterious group known only as the \"Strangers\".",
"title": ""
},
{
"docid": "574909",
"text": "Alien Nation is a 1988 American buddy cop neo-noir science fiction action film directed by Graham Baker. The ensemble cast features James Caan, Mandy Patinkin and Terence Stamp. The film depicts the assimilation of the \"Newcomers\", an alien race settling in Los Angeles, much to the initial dismay of the local population. The plot integrates the neo-noir and buddy cop film genres with a science fiction theme, centering on a union between a veteran police investigator (Caan) and an extraterrestrial (Patinkin); the first Newcomer detective. The duo probe a criminal underworld attempting to solve a homicide.",
"title": ""
},
{
"docid": "25493",
"text": "Sir Ridley Scott (born 30 November 1937) is an English film director and producer. Following his commercial breakthrough with the science-fiction horror film \"Alien\" (1979), his best known works include the neo-noir dystopian science fiction film \"Blade Runner\" (1982), historical drama and Best Picture Oscar winner \"Gladiator\" (2000), and science fiction film \"The Martian\" (2015).",
"title": ""
},
{
"docid": "314444",
"text": "Alexander \"Alex\" Proyas ( ; born 23 September 1963) is an Australian film director, screenwriter, and producer. Proyas is best known for directing the films \"The Crow\" (1994), \"Dark City\" (1998), \"I, Robot\" (2004), \"Knowing\" (2009), and \"Gods of Egypt\" (2016).",
"title": ""
},
{
"docid": "44059",
"text": "Harrison Ford (born July 13, 1942) is an American actor and film producer. He gained worldwide fame for his starring roles as Han Solo in the \"Star Wars\" film series and as the title character of the \"Indiana Jones\" film series. Ford is also known for his roles as Rick Deckard in the neo-noir dystopian science fiction film \"Blade Runner\" (1982); John Book in the thriller \"Witness\" (1985), for which he was nominated for the Academy Award for Best Actor; and Jack Ryan in the action films \"Patriot Games\" (1992) and \"Clear and Present Danger\" (1994).",
"title": ""
},
{
"docid": "234537",
"text": "Equilibrium is a 2002 American dystopian science fiction action film written and directed by Kurt Wimmer and starring Christian Bale, Emily Watson, and Taye Diggs.",
"title": ""
},
{
"docid": "5869916",
"text": "Omega Doom is a 1996 American science-fiction action film directed by Albert Pyun and starring Rutger Hauer. It was written by Pyun and Ed Naha. The story, set in a dystopian future, concerns a robot warrior who, during a nuclear winter, plays both sides of a robot civil war in a small town. The film is mostly based on \"Yojimbo\" by Akira Kurosawa, and it was the third movie in Pyun's \"Cyborg Trilogy\". It is considered a cult film.",
"title": ""
},
{
"docid": "8960083",
"text": "Megaville is an independent/low-budget direct-to-video 1990 American science fiction film, starring Billy Zane in his first lead role. \"Megaville\" is a neo-noir psychological thriller which utilizes elements of science fiction such as cyberpunk and existentialism.",
"title": ""
},
{
"docid": "47404924",
"text": "What Happened to Monday (known as Seven Sisters in France) is a dystopian science fiction thriller film, written by Max Botkin and Kerry Williamson, directed by Tommy Wirkola and starring Noomi Rapace, Glenn Close, and Willem Dafoe. Netflix bought the streaming rights to the film for the United States and other markets. Netflix released the film on August 18, 2017.",
"title": ""
},
{
"docid": "17544255",
"text": "Knowing (stylized as KNOW1NG) is a 2009 science fiction thriller film directed by Alex Proyas and starring Nicolas Cage. The project was originally attached to a number of directors under Columbia Pictures, but it was placed in turnaround and eventually picked up by Escape Artists. Production was financially backed by Summit Entertainment. \"Knowing\" was filmed in Docklands Studios Melbourne, Australia, using various locations to represent the film's Boston-area setting.",
"title": ""
},
{
"docid": "469019",
"text": "Thunderbirds is a 2004 British-American-French science fiction action-adventure film based on the 1960s television series of the same name, directed by Jonathan Frakes. The film, written by William Osborne and Michael McCullers, was released on 24 July 2004 in the United Kingdom and 30 July 2004 in the United States, with later opening dates in other countries. Whereas the original TV series used a form of puppetry termed \"Supermarionation\", the film's characters are portrayed by live-action actors.",
"title": ""
},
{
"docid": "6944155",
"text": "Mark Robert Michael Wahlberg (born June 5, 1971) is an American actor, producer, businessman, former model, and former rapper. Wahlberg was known as Marky Mark in his early career as frontman for the group Marky Mark and the Funky Bunch, releasing the albums \"Music for the People\" and \"You Gotta Believe\". Wahlberg later transitioned to acting, appearing in films such as the drama \"Boogie Nights\" and the satirical war comedy-drama \"Three Kings\" during the 1990s. In the 2000s, he starred in the biographical disaster drama \"The Perfect Storm\", the science fiction film \"Planet of the Apes\", the heist film \"The Italian Job\", and the Martin Scorsese-directed neo-noir crime drama \"The Departed\", for which he received an Academy Award nomination for Best Supporting Actor. In the 2010s, he starred in the action comedy \"The Other Guys\" alongside Will Ferrell, the biographical sports drama \"The Fighter\" (for which he earned an Academy Award nomination as a producer for Best Picture), the comedy \"Ted\", the war film \"Lone Survivor\", the crime comedy \"Pain & Gain\", the science fiction action film \"\" and the sequel \"\", the comedy \"Daddy's Home\", the disaster film \"Deepwater Horizon\", and the thriller \"Patriots Day\".",
"title": ""
},
{
"docid": "406339",
"text": "The Crow is a 1994 American dark fantasy action film directed by Alex Proyas, written by David J. Schow and John Shirley. The film stars Brandon Lee in his final film appearance. The film is based on James O'Barr's 1989 comic book \"The Crow\", and tells the story of Eric Draven (Lee), a rock musician who is revived from the dead to avenge his own death as well as the rape and murder of his fiancée.",
"title": ""
},
{
"docid": "26054678",
"text": "Virtual Revolution is a 2016 indie science fiction film directed and written by Guy-Roger Duvert, and starring Mike Dopud, Jane Badler, Jochen Hägele and Maximilien Poullein.The film is set in dystopian Neo Paris in which people have embraced virtual reality completely.",
"title": ""
},
{
"docid": "2983487",
"text": "Ultraviolet is a 2006 American dystopian science fiction action thriller film written and directed by Kurt Wimmer and produced by Screen Gems. It stars Milla Jovovich as Violet Song, Cameron Bright as Six, and Nick Chinlund as Ferdinand Daxus. It was released in North America on March 3, 2006. The film was released on DVD and Blu-ray Disc on June 27, 2006.",
"title": ""
},
{
"docid": "30007",
"text": "The Matrix is a 1999 science fiction action film written and directed by The Wachowskis, starring Keanu Reeves, Laurence Fishburne, Carrie-Anne Moss, Hugo Weaving, and Joe Pantoliano. It depicts a dystopian future in which reality as perceived by most humans is actually a simulated reality called \"the Matrix\", created by sentient machines to subdue the human population, while their bodies' heat and electrical activity are used as an energy source. Computer programmer Neo learns this truth and is drawn into a rebellion against the machines, which involves other people who have been freed from the \"dream world.\"",
"title": ""
},
{
"docid": "4327099",
"text": "Blade Runner is a 1982 American neo-noir science fiction film directed by Ridley Scott, and starring Harrison Ford, Rutger Hauer, Sean Young, and Edward James Olmos. The film, written by Hampton Fancher and David Peoples, is an adaptation of the 1968 novel \"Do Androids Dream of Electric Sheep?\" by Philip K. Dick.",
"title": ""
},
{
"docid": "44569317",
"text": "The Maze Runner film series consists of science-fiction dystopian action adventure films based on \"The Maze Runner\" novels by the American author James Dashner. Produced by Ellen Goldsmith-Vein and distributed by 20th Century Fox, the films star Dylan O'Brien, Kaya Scodelario, Thomas Brodie-Sangster, Ki Hong Lee, Dexter Darden and Patricia Clarkson. Wes Ball directed all three films.",
"title": ""
},
{
"docid": "826409",
"text": "Collateral is a 2004 American neo-noir crime action thriller directed by Michael Mann and written by Stuart Beattie. It stars Tom Cruise cast against type as a contract killer and Jamie Foxx as a taxi driver who becomes Cruise's hostage during an evening of the hitman's work. The film also features Jada Pinkett Smith and Mark Ruffalo.",
"title": ""
},
{
"docid": "27383563",
"text": "Looper is a 2012 American neo-noir science fiction thriller film written and directed by Rian Johnson, and produced by Ram Bergman and James D. Stern. It stars Bruce Willis, Joseph Gordon-Levitt, and Emily Blunt. It revolves around criminal syndicates using contracted killers called \"loopers\" to kill victims sent through time travel.",
"title": ""
},
{
"docid": "826026",
"text": "Noir is a science fiction novel by K. W. Jeter, published in 1998. It uses the conventions of film noir – the alienated, doomed hero, the cynical private detective, the femme fatale, universal corruption and moral breakdown – to portray a dystopian vision of capitalism run riot.",
"title": ""
},
{
"docid": "46788290",
"text": "Maze Runner: The Death Cure (also known simply as The Death Cure) is an upcoming American dystopian science-fiction action thriller film directed by Wes Ball, based on \"The Death Cure\", the final book in \"The Maze Runner\" trilogy, written by James Dashner, with a screenplay by T.S. Nowlin. It is the sequel to the 2015 film \"\" and the third and final installment in the \"Maze Runner\" film series.",
"title": ""
},
{
"docid": "29446866",
"text": "In Time is a 2011 American dystopian science fiction action thriller film written, directed, and produced by Andrew Niccol and starring Justin Timberlake, Amanda Seyfried and Cillian Murphy that takes place in a society where people stop aging at 25 and each has a clock on their arm that counts down how long they have to live. The film was released on October 28, 2011.",
"title": ""
},
{
"docid": "8776448",
"text": "A Dirty Carnival (; lit: <nowiki></nowiki>\"The Mean Street\"<nowiki></nowiki>) is a South Korean neo-noir action thriller film directed by Yoo Ha. It is Yoo Ha's fourth feature film, his previous work being the 2004 drama, \"Once Upon a Time in High School\".",
"title": ""
},
{
"docid": "30575",
"text": "12 Monkeys, also known as Twelve Monkeys, is a 1995 American neo-noir science fiction film directed by Terry Gilliam, inspired by Chris Marker's 1962 short film \"La Jetée\", and starring Bruce Willis, Madeleine Stowe, and Brad Pitt, with Christopher Plummer and David Morse in supporting roles. After Universal Studios acquired the rights to remake \"La Jetée\" as a full-length film, David and Janet Peoples were hired to write the script.",
"title": ""
},
{
"docid": "27588976",
"text": "I Am Number Four is a 2011 American teen science fiction action thriller film directed by D. J. Caruso and starring Alex Pettyfer, Timothy Olyphant, Teresa Palmer, Dianna Agron, and Callan McAuliffe. The screenplay, by Alfred Gough, Miles Millar, and Marti Noxon, is based on novel of the same name, one of the \"Lorien Legacies\" young adult science fiction novels.",
"title": ""
},
{
"docid": "339403",
"text": "The Omega Man (stylized as The Ωmega Man) is a 1971 American science fiction film directed by Boris Sagal and starring Charlton Heston. It was written by John William Corrington and Joyce Corrington, based on the 1954 novel \"I Am Legend\" by the American writer Richard Matheson. The film's producer, Walter Seltzer, went on to work with Heston again in the dystopian science fiction film \"Soylent Green\" in 1973.",
"title": ""
},
{
"docid": "1051653",
"text": "Rollerball is a 1975 British-American dystopian science fiction sports action film, produced and directed by Norman Jewison, that stars James Caan, John Houseman, Maud Adams, John Beck, Moses Gunn, and Ralph Richardson. The screenplay by William Harrison adapted his own short story, \"Roller Ball Murder\", which had first appeared in the September 1973 issue of \"Esquire.\"",
"title": ""
},
{
"docid": "39321668",
"text": "The Maze Runner is a 2014 American dystopian science fiction action thriller film directed by Wes Ball, in his directorial debut, based on James Dashner's 2009 novel of the same name. The film is the first installment in \"The Maze Runner\" film series and was produced by Ellen Goldsmith-Vein, Wyck Godfrey, Marty Bowen, and Lee Stollman with a screenplay by Noah Oppenheim, Grant Pierce Myers, and T.S. Nowlin. The film stars Dylan O'Brien, Kaya Scodelario, Aml Ameen, Thomas Brodie-Sangster, Ki Hong Lee, Will Poulter, and Patricia Clarkson. The story follows sixteen-year-old Thomas, portrayed by O'Brien, who awakens in a rusty elevator with no memory of who he is, only to learn he's been delivered to the middle of an intricate maze, along with a large number of other boys, who have been trying to find their way out of the ever-changing labyrinth — all while establishing a functioning society in what they call the Glade.",
"title": ""
},
{
"docid": "4882569",
"text": "Yesterday Was a Lie is a 2008 neo-noir film written and directed by James Kerwin and starring Kipleigh Brown, Chase Masterson, John Newton, and Mik Scriba. In publicity materials, the film has been described as a combination of science fantasy and film noir.",
"title": ""
}
] |
PLAIN-3137
|
Improving Mood Through Diet
|
[
{
"docid": "MED-3968",
"text": "Humans have evolved with oral exposure to dietary microparticles and nanoparticles as a normal occurrence but the ever-growing exploitation of nanotechnology is likely to increase exposure further, both qualitatively and quantitatively. Moreover, unlike the situation with respirable particles, relatively little is known about gastrointestinal intake and handling of nanoparticles. With a long term interest in gut exposure and responses to dietary microparticles, our group is now applying its expertise to nanoparticles in the gastrointestinal tract. Here we aim to address (i) the current challenges associated with the characterisation of particle-host or particle-cell interactions, (ii) the origin and mechanisms of uptake of particles in the gastrointestinal tract, especially via the Peyer's patch and (iii) potential cellular effects of nanoparticles in the generation of reactive oxygen species and inflammasome activation, or microparticles in their adjuvant activity in pro-inflammatory signalling and immune responsiveness. Copyright 2010 Elsevier Ltd. All rights reserved.",
"title": "Origin and fate of dietary nanoparticles and microparticles in the gastrointestinal tract."
},
{
"docid": "MED-3542",
"text": "The behavior of inhibitors of monoamine oxidase-A (MAO-A) is considered in terms of the possibility of having an effective antidepressant that does not give rise to hypertensive interactions with dietary tyramine. Studies with punch-biopsy samples of human intestine and rat intestinal samples show MAO-A to be the predominant form of the enzyme in both species. Transport studies with everted rat intestinal preparations indicate that tyramine is extensively metabolized during transport through the intestine. Selective inhibition of MAO-A by clorgyline results in a large increase in the amount of unchanged tyramine transported, whereas selective inhibition of MAO-B with L-deprenyl (selegiline) has no significant effect. The behavior of reversible MAO-A inhibitors can significantly reduce, but not entirely eliminate, these effects on the intestinal metabolism of tyramine, but only if the inhibition is competitive in nature.",
"title": "Monoamine oxidase inhibitors and the cheese effect."
},
{
"docid": "MED-3964",
"text": "BACKGROUND: A better understanding of the environmental factors leading to inflammatory bowel disease should help to prevent occurrence of the disease and its relapses. AIM: To review current knowledge on dietary risk factors for inflammatory bowel disease. METHODS: The PubMed, Medline and Cochrane Library were searched for studies on diet and risk of inflammatory bowel disease. RESULTS: Established non-diet risk factors include family predisposition, smoking, appendectomy, and antibiotics. Retrospective case-control studies are encumbered with methodological problems. Prospective studies on European cohorts, mainly including middle-aged adults, suggest that a diet high in protein from meat and fish is associated with a higher risk of inflammatory bowel disease. Intake of the n-6 polyunsaturated fatty acid linoleic acid may confer risk of ulcerative colitis, whereas n-3 polyunsaturated fatty acids may be protective. No effect was found of intake of dietary fibres, sugar, macronutrients, total energy, vitamin C, D, E, Carotene, or Retinol (vitamin A) on risk of ulcerative colitis. No prospective data was found on risk related to intake of fruits, vegetables or food microparticles (titanium dioxide and aluminium silicate). CONCLUSIONS: A diet high in protein, particular animal protein, may be associated with increased risk of inflammatory bowel disease and relapses. N-6 polyunsaturated fatty acids may predispose to ulcerative colitis whilst n-3 polyunsaturated fatty acid may protect. These results should be confirmed in other countries and in younger subjects before dietary counselling is recommended in high risk subjects. Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.",
"title": "Diet and risk of inflammatory bowel disease."
},
{
"docid": "MED-3965",
"text": "BACKGROUND: Ultrafine and fine particles are potent adjuvants in antigen-mediated immune responses, and cause inflammation in susceptible individuals. Following recent findings that microparticles accumulate in the phagocytes of intestinal lymphoid aggregates, this study is the first investigation of whether their reduction in the diet improves the symptoms of Crohn's disease. METHODS: In a double blind study, 20 patients with active corticosteroid-treated ileal or ileo-colonic Crohn's disease randomly received either a low microparticle diet (trial group; n = 10) or a control diet (n = 10) for 4 months. Crohn's disease activity index (CDAI) and corticosteroid requirements were compared. RESULTS: One patient in each group was withdrawn. In the trial group there was a progressive decrease in CDAI from entry (392 +/- 25) to month 4 (145 +/- 47) (P = 0.002 vs control group) and seven patients were in remission (CDAI <150). In contrast, the control group had returned to baseline levels (302 +/- 28 on entry and 295 +/- 25 at month 4), with none in remission. Corticosteroid intake was reduced more in the trial group although this did not reach significance. CONCLUSIONS: A low microparticle diet may be effective in the management of ileal Crohn's disease and could explain the efficacy of elemental diets, which similarly are low in microparticles.",
"title": "Efficacy and tolerability of a low microparticle diet in a double blind, randomized, pilot study in Crohn's disease."
},
{
"docid": "MED-3963",
"text": "Dietary microparticles are non-biological, bacterial-sized particles. Endogenous sources are derived from intestinal Ca and phosphate secretion. Exogenous sources are mainly titanium dioxide (TiO2) and mixed silicates (Psil); they are resistant to degradation and accumulate in human Peyer's patch macrophages and there is some evidence that they exacerbate inflammation in Crohn's disease (CD). However, whether their intake differs between those with and without CD has not been studied. We aimed to identify dietary microparticle sources and intakes in subjects with and without CD. Patients with inactive CD and matched general practice-based controls (ninety-one per group) completed 7 d food diaries. Intake data for dietary fibre and sucrose were compared as positive controls. All foods, pharmaceuticals and toothpastes were examined for microparticle content, and intakes of Ca and exogenous microparticles were compared between the two groups. Dietary intakes were significantly different between cases and controls for dietary fibre (12 (SD 5) v. 14 (SD 5) g/d; P=0.001) and sucrose (52 (SD 27) v. 45 (SD 18) g/d; P=0.04) but not for Ca. Estimated median TiO2 and Psil intakes (2.5 and 35 mg/individual per d respectively, totalling 10(12)-10(13) microparticles/individual per d) were broadly similar to per capita estimates and while there was wide variation in intakes between individuals there was no significant difference between subjects with CD and controls. Hence, if exposure to microparticles is associated with the inflammation of CD, then the present study rules out excess intake as the problem. Nonetheless, microparticle-containing foods have now been identified which allows a low-microparticle diet to be further assessed in CD.",
"title": "Dietary sources of inorganic microparticles and their intake in healthy subjects and patients with Crohn's disease."
},
{
"docid": "MED-3714",
"text": "The present study was conducted to determine differences in antioxidant levels of fresh, frozen, and freeze-dried strawberries, and strawberry jam. Hydrophilic antioxidant activity (HAA) and lipophilic antioxidant activity (LAA) were measured using the ABTS/H₂O₂/HRP decoloration method. HAA and LAA were then summed to calculate the total antioxidant activity (TAA). Mean differences in HAA and LAA were analyzed using one-way analysis of variance and Dunnett's T3 pairwise comparisons. The mean TAA for freeze-dried strawberries based on an 'as consumed' weight (95% confidence interval [CI]: 29.58, 30.58) was significantly higher than for fresh (95% CI: 3.18, 3.66), frozen (95% CI: 2.58, 2.79), and jam (95% CI: 1.10, 1.22). The mean TAA based on dry weight for fresh strawberries (95% CI: 40.48, 46.67) was significantly higher than for freeze-dried (95% CI: 29.58, 30.58), frozen (95% CI: 24.62, 26.59), and jam (95% CI: 1.48, 1.64). Results agree with previous studies reporting that strawberries are a valuable source of antioxidants for consumers.",
"title": "Differences in antioxidant levels of fresh, frozen and freeze-dried strawberries and strawberry jam."
},
{
"docid": "MED-3962",
"text": "Pathological colonic tissues were investigated with an Environmental Scanning Electron Microscope technique to verify the presence of inorganic, non-biodegradable pollutants, i.e. micro- and nano-debris of exogenous origin, after debris in liver and kidney had been discovered. In all, 18 samples of colon tissues affected by cancer and Crohn's disease were evaluated and found in all the cases to contain micro- and nano-particles. Their chemistry, detected with an X-ray microprobe, indicated a heterogeneous nature, whereas the size of the particles was homogeneous. Three control samples of healthy, young, cadavers were analysed and showed the absence of debris within the normal, healthy colon mucosa. The study reveals the presence of particulate debris, generally considered as biocompatible, in pathological specimens of human colon. The findings suggest a possible link between the presence of such particles and the underlying pathology in the cases analysed.",
"title": "Biocompatibility of micro- and nano-particles in the colon. Part II."
},
{
"docid": "MED-3969",
"text": "Titanium dioxide is a common additive in many food, personal care, and other consumer products used by people, which after use can enter the sewage system, and subsequently enter the environment as treated effluent discharged to surface waters or biosolids applied to agricultural land, incinerated wastes, or landfill solids. This study quantifies the amount of titanium in common food products, derives estimates of human exposure to dietary (nano-) TiO2, and discusses the impact of the nanoscale fraction of TiO2 entering the environment. The foods with the highest content of TiO2 included candies, sweets and chewing gums. Among personal care products, toothpastes and select sunscreens contained 1% to >10% titanium by weight. While some other crèmes contained titanium, despite being colored white, most shampoos, deodorants, and shaving creams contained the lowest levels of titanium (<0.01 μg/mg). For several high-consumption pharmaceuticals, the titanium content ranged from below the instrument detection limit (0.0001 μg Ti/mg) to a high of 0.014 μg Ti/mg. Electron microscopy and stability testing of food-grade TiO2 (E171) suggests that approximately 36% of the particles are less than 100 nm in at least one dimension and that it readily disperses in water as fairly stable colloids. However, filtration of water solubilized consumer products and personal care products indicated that less than 5% of the titanium was able to pass through 0.45 or 0.7 μm pores. Two white paints contained 110 μg Ti/mg while three sealants (i.e., prime coat paint) contained less titanium (25 to 40 μg Ti/mg). This research showed that while many white-colored products contained titanium, it was not a prerequisite. Although several of these product classes contained low amounts of titanium, their widespread use and disposal down the drain and eventually to WWTPs deserves attention. A Monte Carlo human exposure analysis to TiO2 through foods identified children as having the highest exposures because TiO2 content of sweets is higher than other food products, and that a typical exposure for a US adult may be on the order of 1 mg Ti per kilogram body weight per day. Thus, because of the millions of tons of titanium based white pigment used annually, testing should focus on food-grade TiO2 (E171) rather than that adopted in many environmental health and safety tests (i.e., P25), which is used in much lower amounts in products less likely to enter the environment (e.g., catalyst supports, photocatalytic coatings).",
"title": "Titanium Dioxide Nanoparticles in Food and Personal Care Products"
},
{
"docid": "MED-4634",
"text": "OBJECTIVE: Since conventional food questionnaires are not precise in assessing the dietary fatty acids, the purpose of this study was to determine the relationship between the salivary fatty acid profile and the alimentary habits of two different groups in an attempt to develop a more reliable way to determine the lipidic intake. DESIGN: Twenty adults of both sexes, with mixed (M) or vegetarian (V) diets were studied. Data about the fat intake were obtained by means of a Food Frequency Questionnaire (FFQ) and the presence of the main salivary fatty acids was determined by gas chromatography. RESULTS: A greater salivary concentration of alpha-linolenic acid (18:3 n-3) (2.82) was found in V than in M subjects (1.65) (p = 0.001), whilst arachidonic acid (20:4 n-6) was lower in V (3.93) than in M (4.52) (p = 0.045). The same difference regarding arachidonic acid was observed in the dietary fatty acid intake, also showing a significant correlation between its dietary and salivary levels in vegetarian subjects. CONCLUSIONS: These results show that salivary arachidonic acid, relevant for their eicosanoid production related to the tumourigenesis process and cardiovascular diseases, is influenced by dietary fats.",
"title": "Fatty acid profile of human saliva: a possible indicator of dietary fat intake."
},
{
"docid": "MED-3721",
"text": "Reduced expression of proapoptotic and terminal differentiation genes in conjunction with increased levels of the proinflammatory and angiogenesis-inducing enzymes, cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS), correlate with malignant transformation of oral intraepithelial neoplasia (IEN). Accordingly, this study investigated the effects of a 10% (w/w) freeze-dried black raspberry gel on oral IEN histopathology, gene expression profiles, intraepithelial COX-2 and iNOS proteins, and microvascular densities. Our laboratories have shown that freeze-dried black raspberries possess antioxidant properties and also induce keratinocyte apoptosis and terminal differentiation. Oral IEN tissues were hemisected to provide samples for pretreatment diagnoses and establish baseline biochemical and molecular variables. Treatment of the remaining lesional tissue (0.5 g gel applied four times daily for 6 weeks) began 1 week after the initial biopsy. RNA was isolated from snap-frozen IEN lesions for microarray analyses, followed by quantitative reverse transcription-PCR validation. Additional epithelial gene-specific quantitative reverse transcription-PCR analyses facilitated the assessment of target tissue treatment effects. Surface epithelial COX-2 and iNOS protein levels and microvascular densities were determined by image analysis quantified immunohistochemistry. Topical berry gel application uniformly suppressed genes associated with RNA processing, growth factor recycling, and inhibition of apoptosis. Although the majority of participants showed posttreatment decreases in epithelial iNOS and COX-2 proteins, only COX-2 reductions were statistically significant. These data show that berry gel application modulated oral IEN gene expression profiles, ultimately reducing epithelial COX-2 protein. In a patient subset, berry gel application also reduced vascular densities in the superficial connective tissues and induced genes associated with keratinocyte terminal differentiation.",
"title": "Topical Application of a Bioadhesive Black Raspberry Gel Modulates Gene Expression and Reduces Cyclooxygenase 2 Protein in Human Premalignant Oral Lesions"
},
{
"docid": "MED-4632",
"text": "Vegetarians have an apparent diminished risk for the development of ischemic coronary heart disease. This may be secondary to dietary effects of plasma lipids and lipoproteins, but platelets, which may also play a role, have also been observed to have aberrant functions in vegetarians. We measured plasma lipid and lipoprotein levels, platelet function, platelet fatty acid levels, and platelet active prostaglandins in ten strict vegetarians (vegans), 15 lactovegetarians, and 25 age- and sex-matched omnivorous controls. The most striking observations were a highly significant rise in platelet linoleic acid concentration and a decline in platelet arachidonic acid concentration in both vegetarian subgroups as compared with omnivorous controls. Serum thromboxane and prostacyclin levels as well as results of platelet aggregation studies did not differ among the groups tested. Cholesterol levels were significantly lower in both vegetarian groups as compared with controls, but plasma high- and low-density lipoprotein levels were lower only in the vegan subgroup as compared with omnivores. If diet produces these changes in platelet fatty acid and plasma lipid levels it may contribute to the decreased risk of coronary heart disease and possibly atherosclerosis in vegetarians.",
"title": "The effect of vegetarian diets on plasma lipid and platelet levels."
},
{
"docid": "MED-3960",
"text": "Dietary microparticles are non-biological bacterial-sized particles of the gastrointestinal lumen that occur due to endogenous formation (calcium phosphate) or following oral exposure (exogenous microparticle). In the UK, about 40 mg (1012) of exogenous microparticles are ingested per person per day, through exposure to food additives, pharmaceutical/supplement excipients or toothpaste constituents. Once ingested, exogenous microparticles are unlikely to pass through the gastrointestinal tract without adsorbing to their surfaces some ions and molecules of the intestinal lumen. Both entropy and ionic attraction drive such interactions. Calcium ions are especially well adsorbed by dietary microparticles which then provide a positively charged surface for the attraction (adsorption) of other organic molecules such as lipopolysaccharides, peptidoglycans or protein antigen from the diet or commensal flora. The major (but not only) sites of microparticle entry into intestinal tissue are the M-cell rich lymphoid aggregates (termed Peyer’s patches in the small bowel). Indeed, it is well established that this is an efficient transport route for non-biological microparticles although it is unclear why. We hypothesise that this pathway exists for “endogenous microparticles” of calcium phosphate, with immunological and physiological benefit, and that “exogenous dietary microparticles”, such as titanium dioxide and the silicates, hijack this route. This overview focuses on what is known of these microparticles and outlines their potential role in immune tolerance of the gut (endogenous microparticles) or immune activation (exogenous microparticles) and inflammation of the gut.",
"title": "Dietary microparticles and their impact on tolerance and immune responsiveness of the gastrointestinal tract"
},
{
"docid": "MED-3540",
"text": "The 1950s saw the clinical introduction of the first two specifically antidepressant drugs: iproniazid, a monoamine-oxidase inhibitor that had been used in the treatment of tuberculosis, and imipramine, the first drug in the tricyclic antidepressant family. Iproniazid and imipramine made two fundamental contributions to the development of psychiatry: one of a social-health nature, consisting in an authentic change in the psychiatric care of depressive patients; and the other of a purely pharmacological nature, since these agents have constituted an indispensable research tool for neurobiology and psychopharmacology, permitting, among other things, the postulation of the first aetiopathogenic hypotheses of depressive disorders. The clinical introduction of fluoxetine, a selective serotonin reuptake inhibitor, in the late 1980s, once again revolutionized therapy for depression, opening the way for new families of antidepressants. The present work reviews, from a historical perspective, the entire process that led to the discovery of these drugs, as well as their contribution to the development of the neuroscientific disciplines. However, all of these antidepressants, like the rest of those currently available for clinical practice, share the same action mechanism, which involves the modulation of monoaminergic neurotransmission at a synaptic level, so that the future of antidepressant therapy would seem to revolve around the search for extraneuronal non-aminergic mechanisms or mechanisms that modulate the intraneuronal biochemical pathways.",
"title": "Monoaminergic neurotransmission: the history of the discovery of antidepressants from 1950s until today."
},
{
"docid": "MED-3967",
"text": "OBJECTIVE AND DESIGN: Western diets regularly expose the gastrointestinal tract (GI) to large quantities ( > 10(12)/day) of man-made, submicron-sized, particles derived from food additives and excipients. These are taken up by M cells, accumulate in gut macrophages, and may influence the aetiology of inflammatory bowel diseases (IBD). MATERIALS: We investigated the effects of common dietary microparticles on the function of macrophages from healthy donors or active Crohn's disease (CD) patients. METHODS: Macrophages were incubated for 24 h with microparticles before being assayed for cytokine production and phagocytic activity. RESULTS: Microparticles alone were non-stimulatory but, in the presence of bacterial antigens such as LPS, they could act as adjuvants to induce potent cytokine responses. Uptake of high concentrations of microparticles also impaired macrophage phagocytic capacity - but not their ability - to take up 2microM fluorescent beads. CONCLUSIONS: While dietary microparticles alone have limited effects on basic macrophage functions, their ability to act as adjuvants could aggravate ongoing inflammatory responses towards bacterial antigens in the GI tract.",
"title": "Dietary microparticles implicated in Crohn's disease can impair macrophage phagocytic activity and act as adjuvants in the presence of bacterial st..."
},
{
"docid": "MED-3546",
"text": "CONTEXT: The monoamine theory of depression proposes that monoamine levels are lowered, but there is no explanation for how monoamine loss occurs. Monoamine oxidase A (MAO-A) is an enzyme that metabolizes monoamines, such as serotonin, norepinephrine, and dopamine. OBJECTIVE: To determine whether MAO-A levels in the brain are elevated during untreated depression. SETTING: Tertiary care psychiatric hospital. PATIENTS: Seventeen healthy and 17 depressed individuals with major depressive disorder that met entry criteria were recruited from the care of general practitioners and psychiatrists. All study participants were otherwise healthy and nonsmoking. Depressed individuals had been medication free for at least 5 months. MAIN OUTCOME MEASURE: Harmine labeled with carbon 11, a radioligand selective for MAO-A and positron emission tomography, was used to measure MAO-A DVS (specific distribution volume), an index of MAO-A density, in different brain regions (prefrontal cortex, anterior cingulate cortex, posterior cingulate cortex, caudate, putamen, thalamus, anterior temporal cortex, midbrain, hippocampus, and parahippocampus). RESULTS: The MAO-A DVS was highly significantly elevated in every brain region assessed (t test; P=.001 to 3x10(-7)). The MAO-A DVS was elevated on average by 34% (2 SDs) throughout the brain during major depression. CONCLUSIONS: The sizable magnitude of this finding and the absence of other compelling explanations for monoamine loss during major depressive episodes led to the conclusion that elevated MAO-A density is the primary monoamine-lowering process during major depression.",
"title": "Elevated monoamine oxidase a levels in the brain: an explanation for the monoamine imbalance of major depression."
},
{
"docid": "MED-3961",
"text": "BACKGROUND AND AIMS: Dietary microparticles, which are bacteria-sized and non-biological, found in the modern Western diet, have been implicated in both the aetiology and pathogenesis of Crohn's disease. Following on from the findings of a previous pilot study, we aimed to confirm whether a reduction in the amount of dietary microparticles facilitates induction of remission in patients with active Crohn's disease, in a single-blind, randomized, multi-centre, placebo controlled trial. METHODS: Eighty-three patients with active Crohn's disease were randomly allocated in a 2 x 2 factorial design to a diet low or normal in microparticles and/or calcium for 16 weeks. All patients received a reducing dose of prednisolone for 6 weeks. Outcome measures were Crohn's disease activity index, Van Hees index, quality of life and a series of objective measures of inflammation including erythrocyte sedimentation rate, C-reactive protein, intestinal permeability and faecal calprotectin. After 16 weeks patients returned to their normal diet and were followed up for a further 36 weeks. RESULTS: Dietary manipulation provided no added effect to corticosteroid treatment on any of the outcome measures during the dietary trial (16 weeks) or follow-up (to 1 year); e.g., for logistic regression of Crohn's disease activity index based rates of remission (P=0.1) and clinical response (P=0.8), in normal versus low microparticle groups. CONCLUSIONS: Our adequately powered and carefully controlled dietary trial found no evidence that reducing microparticle intake aids remission in active Crohn's disease.",
"title": "Lack of efficacy of a reduced microparticle diet in a multi-centred trial of patients with active Crohn's disease."
},
{
"docid": "MED-3547",
"text": "Monoamine theories associate depression with reduced brain monoamine levels. These theories achieved broad popularity in the mid-1960s. The present article reviews the historical development of monoamine theories and their subsequent impact on biomedical research. Alleged divisions between West European and US researchers over competing versions of the theories are investigated using bibliometrics. Subsequently, the application of monoamine theories in the NIMH Collaborative Program on the Psychobiology of Depression is covered. The article argues that the impact of monoamine theories is best explained by the ability of researchers, governmental agencies, and pharmaceutical companies to invoke theories that advance various projects and agendas.",
"title": "Monoamine theories of depression: historical impact on biomedical research."
},
{
"docid": "MED-3720",
"text": "Black raspberries are a rich natural source of chemopreventive phytochemicals. Recent studies have shown that freeze-dried black raspberries inhibit the development of oral, esophageal, and colon cancer in rodents, and extracts of black raspberries inhibit benzo(a)pyrene-induced cell transformation of hamster embryo fibroblasts. However, the molecular mechanisms and the active components responsible for black raspberry chemoprevention are unclear. In this study, we found that 2 major chemopreventive components of black raspberries, ferulic acid and beta-sitosterol, and a fraction eluted with ethanol (RO-ET) during silica column chromatography of the organic extract of freeze-dried black raspberries inhibit the growth of premalignant and malignant but not normal human oral epithelial cell lines. Another fraction eluted with CH2Cl2/ethanol (DM:ET) and ellagic acid inhibited the growth of normal as well as premalignant and malignant human oral cell lines. We investigated the molecular mechanisms by which ferulic acid and beta-sitosterol and the RO-ET fraction selectively inhibited the growth of premalignant and malignant oral cells using flow cytometry and Western blotting of cell cycle regulatory proteins. There was no discernable change in the cell cycle distribution following treatment of cells with the RO-ET fraction. Premalignant and malignant cells redistributed to the G2/M phase of the cell cycle following incubation with ferulic acid. beta-sitosterol treated premalignant and malignant cells accumulated in the G0/G1 and G2/M phases, respectively. The RO-ET fraction reduced the levels of cyclin A and cell division cycle gene 2 (cdc2) in premalignant cells and cyclin B1, cyclin D1, and cdc2 in the malignant cell lines. This fraction also elevated the levels of p21waf1/cip1 in the malignant cell line. Ferulic acid treatment led to increased levels of cyclin B1 and cdc2 in both cell lines, and p21waf1/cip1 was induced in the malignant cell line. beta-sitosterol reduced the levels of cyclin B1 and cdc2 while increasing p21waf1/cip1 in both the premalignant and malignant cell lines. These results show for the first time that the growth inhibitory effects of black raspberries on premalignant and malignant human oral cells may reside in specific components that target aberrant signaling pathways regulating cell cycle progression.",
"title": "Inhibition of the growth of premalignant and malignant human oral cell lines by extracts and components of black raspberries."
},
{
"docid": "MED-4633",
"text": "Background The physical health status of vegetarians has been extensively reported, but there is limited research regarding the mental health status of vegetarians, particularly with regard to mood. Vegetarian diets exclude fish, the major dietary source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), critical regulators of brain cell structure and function. Omnivorous diets low in EPA and DHA are linked to impaired mood states in observational and experimental studies. Methods We examined associations between mood state and polyunsaturated fatty acid intake as a result of adherence to a vegetarian or omnivorous diet in a cross-sectional study of 138 healthy Seventh Day Adventist men and women residing in the Southwest. Participants completed a quantitative food frequency questionnaire, Depression Anxiety Stress Scale (DASS), and Profile of Mood States (POMS) questionnaires. Results Vegetarians (VEG:n = 60) reported significantly less negative emotion than omnivores (OMN:n = 78) as measured by both mean total DASS and POMS scores (8.32 ± 0.88 vs 17.51 ± 1.88, p = .000 and 0.10 ± 1.99 vs 15.33 ± 3.10, p = .007, respectively). VEG reported significantly lower mean intakes of EPA (p < .001), DHA (p < .001), as well as the omega-6 fatty acid, arachidonic acid (AA; p < .001), and reported higher mean intakes of shorter-chain α-linolenic acid (p < .001) and linoleic acid (p < .001) than OMN. Mean total DASS and POMS scores were positively related to mean intakes of EPA (p < 0.05), DHA (p < 0.05), and AA (p < 0.05), and inversely related to intakes of ALA (p < 0.05), and LA (p < 0.05), indicating that participants with low intakes of EPA, DHA, and AA and high intakes of ALA and LA had better mood. Conclusions The vegetarian diet profile does not appear to adversely affect mood despite low intake of long-chain omega-3 fatty acids.",
"title": "Vegetarian diets are associated with healthy mood states: a cross-sectional study in Seventh Day Adventist adults"
},
{
"docid": "MED-3545",
"text": "Background Omnivorous diets are high in arachidonic acid (AA) compared to vegetarian diets. Research shows that high intakes of AA promote changes in brain that can disturb mood. Omnivores who eat fish regularly increase their intakes of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), fats that oppose the negative effects of AA in vivo. In a recent cross-sectional study, omnivores reported significantly worse mood than vegetarians despite higher intakes of EPA and DHA. This study investigated the impact of restricting meat, fish, and poultry on mood. Findings Thirty-nine omnivores were randomly assigned to a control group consuming meat, fish, and poultry daily (OMN); a group consuming fish 3-4 times weekly but avoiding meat and poultry (FISH), or a vegetarian group avoiding meat, fish, and poultry (VEG). At baseline and after two weeks, participants completed a food frequency questionnaire, the Profile of Mood States questionnaire and the Depression Anxiety and Stress Scales. After the diet intervention, VEG participants reduced their EPA, DHA, and AA intakes, while FISH participants increased their EPA and DHA intakes. Mood scores were unchanged for OMN or FISH participants, but several mood scores for VEG participants improved significantly after two weeks. Conclusions Restricting meat, fish, and poultry improved some domains of short-term mood state in modern omnivores. To our knowledge, this is the first trial to examine the impact of restricting meat, fish, and poultry on mood state in omnivores.",
"title": "Restriction of meat, fish, and poultry in omnivores improves mood: A pilot randomized controlled trial"
},
{
"docid": "MED-3970",
"text": "Various specific and non-specific environmental factors have been associated with the induction and/or exacerbation of disease activity in patients with Crohn's disease and ulcerative colitis. One such factor is the potential role of ingested ultrafine particles. In fact, based on a Western diet, recent data suggest that more than 10(12)ultrafine particles are ingested per person every day. These microparticles have been considered inert although they adsorb endogenous constituents of the intestinal lumen and are taken up by human intestinal lymphoid aggregates. Based on these observations, we determined whether one such dietary microparticle, titanium dioxide (TiO(2)), alters intestinal cell responsiveness to lipopolysaccharide (LPS) using colonic biopsy specimens from 28 patients with ulcerative colitis, 21 with Crohn's disease, and 36 healthy controls. These samples, as well as peripheral blood mononuclear cells when available, were incubated alone (control), or with either (a) LPS (1-2,000 ng/ml), (b) TiO(2)(5 microg/ml) or (c) LPS (1 ng/ml) adsorbed to TiO(2)(5 microg/ml). In each case, the levels of interleukin 1 (IL-1) produced in these assays were quantitated by bioassay and by ELISA. Interestingly, there was dramatic stimulation of peripheral blood mononuclear cells using the TiO(2)-LPS conjugate, with values 30-60-fold above controls and only minor stimulation with LPS or TiO(2)alone. In intestinal organ cultures there was no increase in IL-1 secretion when challenged with TiO(2)alone or with up to 2,000 ng/ml LPS. However, the TiO(2)-LPS conjugate produced a two-to-three-fold, significant increase in the intestinal secretion of IL-1. Our data demonstrate that ultrafine dietary particles are not immunologically inert and may be important adjuncts in overcoming normal gut cell hyporesponsiveness to endogenous luminal molecules. This may be particularly relevant to patients with inflammatory bowel disease where there is abnormal intestinal permeability. Copyright 2000 Academic Press.",
"title": "Immune potentiation of ultrafine dietary particles in normal subjects and patients with inflammatory bowel disease."
},
{
"docid": "MED-3543",
"text": "Inhibition of monoamine oxidase is one way to treat depression and anxiety. The information now available on the pharmacokinetics of flavonoids and of the components of tobacco prompted an exploration of whether a healthy diet (with or without smoking) provides active compounds in amounts sufficient to partially inhibit monoamine oxidase. A literature search was used to identify dietary monoamine oxidase inhibitors, the levels of these compounds in foods, the pharmacokinetics of the absorption and distribution, and tissue levels observed. An estimated daily intake and the expected tissue concentrations were compared with the measured efficacies of the compounds as inhibitors of monoamine oxidases. Norharman, harman and quercetin dietary presence, pharmacokinetics, and tissue levels were consistent with significant levels reaching neuronal monoamine oxidase from the diet or smoking; 1,2,3,4-tetrahydroisoquinoline, eugenol, 1-piperoylpiperidine, and coumarin were not. Quercetin was equipotent with norharman as a monoamine oxidase A inhibitor and its metabolite, isorhamnetin, also inhibits. Total quercetin was the highest of the compounds in the sample diet. Although bioavailability was variable depending on the source, a healthy diet contains amounts of quercetin that might give sufficient amounts in brain to induce, by monoamine oxidase A inhibition, a small decrease in neurotransmitter breakdown.",
"title": "Dietary inhibitors of monoamine oxidase A."
},
{
"docid": "MED-3966",
"text": "Crohn's disease is a modern Western disease characterised by transmural inflammation of the gastrointestinal tract. It is of unknown aetiology, but evidence suggests that it results from a combination of genetic predisposition and environmental factors. Bacterial-sized microparticles (0.1-1.0 microm) are potent adjuvants in model antigen-mediated immune responses and are increasingly associated with disease. Microparticles of TiO2 and aluminosilicate accumulate in macrophages of human gut-associated lymphoid tissue where the earliest signs of lesions in Crohn's disease are observed. Dietary microparticles are of endogenous or exogenous origin. Endogenous microparticles dominate and are calcium phosphate (most probably hydroxyapatite), which precipitates in the lumen of the mid-distal gastrointestinal tract due to secretion of Ca and phosphate in the succus entericus. Exogenous dietary microparticles are contaminants (soil and/or dust) and food additives. TiO2, for example, is a food colourant, and aluminosilicates are anti-caking agents, although some aluminosilicates occur as natural contaminants. Food additives alone account for ingestion of approximately 10(12) particles/person per d. Possible mechanisms for the role of exogenous and endogenous dietary microparticles in promoting toleragenic or immune responses of gastrointestinal mucosal phagocytosis are discussed. In a double-blind randomised pilot study we have shown that a diet low in Ca and exogenous microparticles appears to alleviate the symptoms of ileal Crohn's disease, with a significant (P= 0.002) improvement in the Crohn's disease activity index. A multi-centre trial and further mechanistic studies at the cellular level are underway.",
"title": "Fine and ultrafine particles of the diet: influence on the mucosal immune response and association with Crohn's disease."
},
{
"docid": "MED-3544",
"text": "Whole-body PET-scan studies in brains of tobacco smokers have shown a decrease in monoamine oxidase (MAO) activity, which reverts to control level when they quit smoking. The observed decrease in MAO activity in smokers is presumably due to their exposure to tobacco constituents that possess MAO-inhibiting properties. The inhibition of MAO activity seems, however, not to be a unique feature of tobacco smoking as subjects with Type II alcoholism have been reported to show a similar decrease in MAO activity that reverses when they cease to use alcohol. The present review summarizes the data on MAO-inhibiting tobacco constituents and explains that the decrease in MAO activity observed in alcoholics is probably due to concomitant tobacco use. It is concluded that the inhibition of MAO by constituents contained in tobacco and tobacco smoke, enhances the addiction induced by tobacco smoking.",
"title": "Contribution of monoamine oxidase (MAO) inhibition to tobacco and alcohol addiction."
},
{
"docid": "MED-3541",
"text": "OBJECTIVE: The study evaluated the association between consumption frequencies of the major food categories and the risk of new depression four years later in older Taiwanese. DESIGN: A prospective cohort study with multistage random sampling. Logistic regression analysis evaluated the significance of the longitudinal associations of intake frequencies of the major food categories with future (4 years later) risk of new depression, controlled for possible confounding factors with or without adjustment for cognitive status. SETTING: Population-based free-living elderly. SUBJECTS: Men and women (n 1609) ≥65 years of age. RESULTS: In a regression model that controlled for demographic, socio-economic, lifestyle and disease/health-related variables but not cognitive status, both fruits (OR = 0·66, 95 % CI 0·45, 0·98, P = 0·038) and vegetables (OR = 0·38, 95 % CI 0·17, 0·86, P = 0·021) were protective against depressive symptoms 4 years later. However, when the same regression model was also adjusted for cognitive status, only vegetables (OR = 0·40, 95 % CI 0·17, 0·95, P = 0·039) were protective against depressive symptoms. Higher consumption of eggs was close to being significant in both regression models (P = 0·087 and 0·069, respectively). Other food categories including meat/poultry, fish, seafood, dairy, legumes, grains and tea showed no significant associations. CONCLUSIONS: Results suggest that although confounding factors cannot be totally ruled out, more frequent consumption of vegetables seems to be protective against depressive symptoms in the elderly. Further studies are needed to elucidate the causal role and the mechanism of the association.",
"title": "Frequent consumption of vegetables predicts lower risk of depression in older Taiwanese - results of a prospective population-based study."
}
] |
[
{
"docid": "MED-2707",
"text": "Essential oils have been used as remedies for a long time in different cultures across the world. However, scientific proof of such application is scarce. We included 72 patients between the ages of 22 and 57 while waiting for dental treatment in our study. The participants were assigned to either a control group (14 men, 23 women) or to an odor group (18 men and 17 women). Ambient odor of orange was diffused in the waiting room through an electrical dispenser in the odor group whereas in the control group no odor was in the air. We assessed by means of self-report demographic and cognitive variables, trait and state anxiety, and current pain, mood, alertness, and calmness. In this study, we report that exposure to ambient odor of orange has a relaxant effect. Specifically, compared to the controls, women who were exposed to orange odor had a lower level of state anxiety, a more positive mood, and a higher level of calmness. Our data support the previous notion of sedative properties of the natural essential oil of orange (Citrus sinensis).",
"title": "Ambient odor of orange in a dental office reduces anxiety and improves mood in female patients."
},
{
"docid": "MED-1299",
"text": "OBJECTIVE: Several studies have shown a baker's yeast beta-1,3/1,6-d-glucan, extracted from Saccharomyces cerevisiae, is effective in reducing the incidence of cold and flu symptoms. This study evaluated the effect of a specific beta-glucan supplement (Wellmune) on upper respiratory tract symptoms and psychological well-being in women with moderate levels of psychological stress. METHODS: Healthy women (38 ± 12 years old) prescreened for moderate levels of psychological stress, self-administered a placebo (n = 38) or 250 mg of Wellmune (n = 39) daily for 12 weeks. We used the Profile of Mood States (POMS) psychological survey to assess changes in mental/physical energy levels (vigor) and overall well-being (global mood state). A quantitative health perception log was used to track upper respiratory symptoms. RESULTS: Subjects in the Wellmune group reported fewer upper respiratory symptoms compared to placebo (10% vs 29%), better overall well-being (global mood state: 99 ± 19 vs 108 ± 23, p < 0.05), and superior mental/physical energy levels (vigor: 19.9 ± 4.7 vs 15.8 ± 6.3, p < 0.05). CONCLUSIONS: These data show that daily dietary supplementation with Wellmune reduces upper respiratory symptoms and improves mood state in stressed subjects, and thus it may be a useful approach for maintaining immune protection against daily stressors.",
"title": "Baker's yeast beta-glucan supplement reduces upper respiratory symptoms and improves mood state in stressed women."
},
{
"docid": "MED-4305",
"text": "Influence of diet composition on mood during weight-reducing diets was studied in healthy young women of normal weight. A broad range of macronutrient intake was achieved by means of divergent dietary instructions for the composition of a 1,000 kcal per day diet adhered to for six weeks. Global mood during the last three weeks of the diet was significantly better in the \"vegetarian\" than in the \"mixed\" diet group. During this time a significant correlation was observed between relative carbohydrate intake and global mood (r = -0.74; p less than 0.01) and between the ratio of plasma tryptophan to other large neutral amino acids (a predictor of tryptophan flow into brain) and global mood (r = -0.52; p less than 0.05). Results suggest that group differences are related to differences in carbohydrate intake. It is hypothesized that impairment of central serotonergic function due to reduced tryptophan availability can prompt mood deterioration in situations of relatively low carbohydrate intake.",
"title": "Macronutrient intake, plasma large neutral amino acids and mood during weight-reducing diets."
},
{
"docid": "MED-4308",
"text": "We examined the occurrence and coincidence of depressed mood and excessive carbohydrate intake in 19 patients who claimed to suffer from severe premenstrual syndrome and in nine control subjects, all as inpatients, during the early follicular and late luteal phases of their menstrual cycles. Mood was assessed with the Hamilton Depression Scale and an addendum that evaluated fatigue, sociability, appetite, and carbohydrate craving. Calorie and nutrient intakes were measured directly. The subjects with premenstrual syndrome significantly increased calorie intake during the late luteal phase (from 1892 +/- 104 to 2395 +/- 93 kcal, mean +/- SEM); carbohydrate intake increased by 24% from meals and by 43% from snacks. Protein intake failed to change, whereas intake of fat, a fixed constituent of all of the test foods, rose in proportion to calorie intake. The Hamilton Depression Scale and addendum scores rose from 2.0 +/- 0.5 to 21.2 +/- 0.8 (Hamilton Scale) and from 0.5 +/- 0.5 to 10.2 +/- 0.6 (addendum) among subjects with premenstrual syndrome during the luteal phase but failed to change among the controls (2.1 +/- 0.8 to 2.4 +/- 0.8, and 0.4 +/- 0.3 to 0.6 +/- 0.3). Consumption of a carbohydrate-rich, protein-poor evening test meal during the late luteal phase of the menstrual cycle improved depression, tension, anger, confusion, sadness, fatigue, alertness, and calmness scores (p less than 0.01) among patients with premenstrual syndrome. No effect of the meal was observed during the follicular phase or among the control subjects during either phase. Because synthesis of brain serotonin, which is known to be involved in mood and appetite, increases after carbohydrate intake, premenstrual syndrome subjects may overconsume carbohydrates in an attempt to improve their dysphoric mood state.",
"title": "Effect of nutrient intake on premenstrual depression."
},
{
"docid": "MED-5342",
"text": "Background The physical health status of vegetarians has been extensively reported, but there is limited research regarding the mental health status of vegetarians, particularly with regard to mood. Vegetarian diets exclude fish, the major dietary source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), critical regulators of brain cell structure and function. Omnivorous diets low in EPA and DHA are linked to impaired mood states in observational and experimental studies. Methods We examined associations between mood state and polyunsaturated fatty acid intake as a result of adherence to a vegetarian or omnivorous diet in a cross-sectional study of 138 healthy Seventh Day Adventist men and women residing in the Southwest. Participants completed a quantitative food frequency questionnaire, Depression Anxiety Stress Scale (DASS), and Profile of Mood States (POMS) questionnaires. Results Vegetarians (VEG:n = 60) reported significantly less negative emotion than omnivores (OMN:n = 78) as measured by both mean total DASS and POMS scores (8.32 ± 0.88 vs 17.51 ± 1.88, p = .000 and 0.10 ± 1.99 vs 15.33 ± 3.10, p = .007, respectively). VEG reported significantly lower mean intakes of EPA (p < .001), DHA (p < .001), as well as the omega-6 fatty acid, arachidonic acid (AA; p < .001), and reported higher mean intakes of shorter-chain α-linolenic acid (p < .001) and linoleic acid (p < .001) than OMN. Mean total DASS and POMS scores were positively related to mean intakes of EPA (p < 0.05), DHA (p < 0.05), and AA (p < 0.05), and inversely related to intakes of ALA (p < 0.05), and LA (p < 0.05), indicating that participants with low intakes of EPA, DHA, and AA and high intakes of ALA and LA had better mood. Conclusions The vegetarian diet profile does not appear to adversely affect mood despite low intake of long-chain omega-3 fatty acids.",
"title": "Vegetarian diets are associated with healthy mood states: a cross-sectional study in Seventh Day Adventist adults"
},
{
"docid": "MED-939",
"text": "Snacking is an uncontrolled eating behavior, predisposing weight gain and obesity. It primarily affects the female population and is frequently associated with stress. We hypothesized that oral supplementation with Satiereal (Inoreal Ltd, Plerin, France), a novel extract of saffron stigma, may reduce snacking and enhance satiety through its suggested mood-improving effect, and thus contribute to weight loss. Healthy, mildly overweight women (N = 60) participated in this randomized, placebo-controlled, double-blind study that evaluated the efficacy of Satiereal supplementation on body weight changes over an 8-week period. Snacking frequency, the main secondary variable, was assessed by daily self-recording of episodes by the subjects in a nutrition diary. Twice a day, enrolled subjects consumed 1 capsule of Satiereal (176.5 mg extract per day (n = 31) or a matching placebo (n = 29). Caloric intake was left unrestricted during the study. At baseline, both groups were homogeneous for age, body weight, and snacking frequency. Satiereal caused a significantly greater body weight reduction than placebo after 8 weeks (P < .01). The mean snacking frequency was significantly decreased in the Satiereal group as compared with the placebo group (P < .05). Other anthropometric dimensions and vital signs remained almost unchanged in both groups. No subject withdrawal attributable to a product effect was reported throughout the trial, suggesting a good tolerability to Satiereal. Our results indicate that Satiereal consumption produces a reduction of snacking and creates a satiating effect that could contribute to body weight loss. The combination of an adequate diet with Satiereal supplementation might help subjects engaged in a weight loss program in achieving their objective. Copyright 2010 Elsevier Inc. All rights reserved.",
"title": "Satiereal, a Crocus sativus L extract, reduces snacking and increases satiety in a randomized placebo-controlled study of mildly overweight, health..."
},
{
"docid": "MED-3153",
"text": "This was a placebo-controlled, double-blind study designed to evaluate the effect of a commercially available dietary supplement on upper-respiratory tract symptoms (URTI) and mood state. Seventy-five marathon runners (35 men, 40 women) ranging in age from 18-53 years, mean age: 36 ± 9, self-administered placebo, 250 mg or 500 mg of BETA 1,3/1,6 GLUCAN (commercial name Wellmune WGP®) daily during the 4 week post-marathon trial period following the 2007 Carlsbad Marathon. Subjects filled out the profile of mood state (POMS) assessment and a questionnaire style health log measuring health status and URTI symptoms after 2- and 4-week treatment administrations. During the course of the 4-week study, subjects in the treatment groups (250 mg and 500 mg BETA-GLUCAN per day) reported significantly fewer URTI symptoms, better overall health and decreased confusion, fatigue, tension, and anger, and increased vigor based on the POMS survey compared to placebo. BETA-GLUCAN may prevent URTI symptoms, and improve overall health and mood following a competitive marathon. Key points",
"title": "Effect of BETA 1, 3/1, 6 GLUCAN on Upper Respiratory Tract Infection Symptoms and Mood State in Marathon Athletes"
},
{
"docid": "MED-1198",
"text": "BACKGROUND: Ascorbic acid (AA) modulates catecholaminergic activity, decreases stress reactivity, approach anxiety and prolactin release, improves vascular function, and increases oxytocin release. These processes are relevant to sexual behavior and mood. METHODS: In this randomized double-blind, placebo-controlled 14 day trial of sustained-release AA (42 healthy young adults; 3000 mg/day Cetebe) and placebo (39 healthy young adults), subjects with partners recorded penile-vaginal intercourse (FSI), noncoital partner sex, and masturbation in daily diaries, and also completed the Beck Depression Inventory before and after the trial. RESULTS: The AA group reported greater FSI (but, as hypothesized, not other sexual behavior) frequency, an effect most prominent in subjects not cohabiting with their sexual partner, and in women. The AA but not placebo group also experienced a decrease in Beck Depression scores. CONCLUSIONS: AA appears to increase FSI, and the differential benefit to noncohabitants suggests that a central activation or disinhibition, rather than peripheral mechanism may be responsible.",
"title": "High-dose ascorbic acid increases intercourse frequency and improves mood: a randomized controlled clinical trial."
},
{
"docid": "MED-3665",
"text": "There is widespread belief that the use of aromatherapy and massage in an intensive care environment offers a means of increasing the quality of sensory input that patients receive, as well as reducing levels of stress and anxiety. Despite a wealth of anecdotal evidence in support of these claims, there have been few objective studies to evaluate the effects of these therapies. In this experimental study 122 patients admitted to a general intensive care unit were randomly allocated to receive either massage, aromatherapy using essential oil of lavender, or a period of rest. Both pre- and post-therapy assessments included physiological stress indicators and patients' evaluation of their anxiety levels, mood and ability to cope with their intensive care experience. Ninety-three patients (77%) were able to complete subjective assessments. There were no statistically significant differences in the physiological stress indicators or observed or reported behaviour of patients' ability to cope following any of the three interventions. However, those patients who received aromatherapy reported significantly greater improvement in their mood and perceived levels of anxiety. They also felt less anxious and more positive immediately following the therapy, although this effect was not sustained or cumulative.",
"title": "Sensing an improvement: an experimental study to evaluate the use of aromatherapy, massage and periods of rest in an intensive care unit."
},
{
"docid": "MED-1630",
"text": "Despite its widespread use, the artificial sweetener aspartame remains one of the most controversial food additives, due to mixed evidence on its neurobehavioral effects. Healthy adults who consumed a study-prepared high-aspartame diet (25 mg/kg body weight/day) for 8 days and a low-aspartame diet (10 mg/kg body weight/day) for 8 days, with a 2-week washout between the diets, were examined for within-subject differences in cognition, depression, mood, and headache. Measures included weight of foods consumed containing aspartame, mood and depression scales, and cognitive tests for working memory and spatial orientation. When consuming high-aspartame diets, participants had more irritable mood, exhibited more depression, and performed worse on spatial orientation tests. Aspartame consumption did not influence working memory. Given that the higher intake level tested here was well below the maximum acceptable daily intake level of 40-50 mg/kg body weight/day, careful consideration is warranted when consuming food products that may affect neurobehavioral health. © 2014 Wiley Periodicals, Inc.",
"title": "Neurobehavioral effects of aspartame consumption."
},
{
"docid": "MED-3810",
"text": "The typical spices used in winter include nutmeg, cinnamon, clove and anise. These spices contain two groups of chemicals, the allylbenzenes and their isomers, the propenylbenzenes. It was suggested 40 years ago by Alexander Shulgin that these substances act as metabolic precursors of amphetamines. The biotransformation of these precursors to nitrogen-containing metabolites is reviewed. These reactions have not been reported in humans. Whether or not the pharmacology and toxicology of spices such as nutmeg can be explained on the basis of their allylbenzene or propenylbenzene content is speculative. Humans may be exposed to amphetamines derived from these precursors in forno, the formation during baking and cooking, for example in the preparation of Lebkuchen, or Christmas gingerbread. It is possible that this may be responsible, in part, for uplifting our mood in winter. However, the role of these aromatic substances, acting simply as odours, evoking old memories of winters past, cannot be ignored. Whether spices have a true pharmacological effect or they act as aromatherapy remains to be elucidated through clinical and laboratory studies.",
"title": "Christmas gingerbread (Lebkuchen) and Christmas cheer--review of the potential role of mood elevating amphetamine-like compounds formed in vivo and..."
},
{
"docid": "MED-1617",
"text": "Background Dietary modification via caloric restriction is associated with multiple effects related to improved metabolic and cardiovascular health. However, a mandated reduction in kilocalories is not well-tolerated by many individuals, limiting the long-term application of such a plan. The Daniel Fast is a widely utilized fast based on the Biblical book of Daniel. It involves a 21 day ad libitum food intake period, devoid of animal products and preservatives, and inclusive of fruits, vegetables, whole grains, legumes, nuts, and seeds. The purpose of the present study was to determine the efficacy of the Daniel Fast to improve markers of metabolic and cardiovascular disease risk. Methods 43 subjects (13 men; 30 women; 35 ± 1 yrs; range: 20-62 yrs) completed a 21 day period of modified food intake in accordance with detailed guidelines provided by investigators. All subjects purchased and prepared their own food. Following initial screening, subjects were given one week to prepare for the fast, after which time they reported to the lab for their pre-intervention assessment (day 1). After the 21 day fast, subjects reported to the lab for their post-intervention assessment (day 22). For both visits, subjects reported in a 12 hr fasted state, performing no strenuous physical activity during the preceding 24-48 hrs. At each visit, mental and physical health (SF-12 form), resting heart rate and blood pressure, and anthropometric variables were measured. Blood was collected for determination of complete blood count, metabolic panel, lipid panel, insulin, HOMA-IR, and C-reactive protein (CRP). Subjects' self-reported compliance, mood, and satiety in relation to the fast were also recorded. Diet records were maintained by all subjects during the 7 day period immediately prior to the fast (usual intake) and during the final 7 days of the fast. Results Subjects' compliance to the fast was 98.7 ± 0.2% (mean ± SEM). Using a 10 point scale, subjects' mood and satiety were both 7.9 ± 0.2. The following variables were significantly (p < 0.05) lower following the fast as compared to before the fast: white blood cell count (5.68 ± 0.24 vs. 4.99 ± 0.19 103·μL-1), blood urea nitrogen (13.07 ± 0.58 vs. 10.14 ± 0.59 mg·dL-1), blood urea nitrogen/creatinine (14.74 ± 0.59 vs. 11.67 ± 0.68), protein (6.95 ± 0.07 vs. 6.77 ± 0.06 g·dL-1), total cholesterol (171.07 ± 4.57 vs. 138.69 ± 4.39 mg·dL-1), LDL-C (98.38 ± 3.89 vs. 76.07 ± 3.53 mg·dL-1), HDL-C (55.65 ± 2.50 vs. 47.58 ± 2.19 mg·dL-1), SBP (114.65 ± 2.34 vs. 105.93 ± 2.12 mmHg), and DBP (72.23 ± 1.59 vs. 67.00 ± 1.43 mmHg). Insulin (4.42 ± 0.52 vs. 3.37 ± 0.35 μU·mL-1; p = 0.10), HOMA-IR (0.97 ± 0.13 vs.0.72 ± 0.08; p = 0.10), and CRP (3.15 ± 0.91 vs. 1.60 ± 0.42 mg·L-1; p = 0.13), were lowered to a clinically meaningful, albeit statistically insignificant extent. No significant difference was noted for any anthropometric variable (p > 0.05). As expected, multiple differences in dietary intake were noted (p < 0.05), including a reduction in total kilocalorie intake (2185 ± 94 vs. 1722 ± 85). Conclusion A 21 day period of modified dietary intake in accordance with the Daniel Fast is 1) well-tolerated by men and women and 2) improves several risk factors for metabolic and cardiovascular disease. Larger scale, randomized studies, inclusive of a longer time period and possibly a slight modification in food choice in an attempt to maintain HDL cholesterol, are needed to extend these findings.",
"title": "Effect of a 21 day Daniel Fast on metabolic and cardiovascular disease risk factors in men and women"
},
{
"docid": "MED-3038",
"text": "The effects of 50 mg naltrexone on eating and subjective appetite were assessed in a double-blind placebo-controlled study with 20 male volunteers. Appetite was monitored using a disguised digital balance connected to a micro-computer, which constantly monitored the amount of food remaining, and which automatically interrupted feeding for 30 s after every 50 g consumed to allow appetite ratings to be made. Half the subjects ate pasta with a cheese sauce, and the remainder pasta with a tomato sauce. Subjects ate significantly less of both foods after 50 mg naltrexone than in either the placebo condition or on the initial (familiarisation) day. Naltrexone also reduced the rated pleasantness of both foods, and reduced overall eating rate. When best-fit quadratic functions were used to describe changes in rated hunger in relation to intake within the meal, naltrexone abolished the positive linear component reflecting the initial stimulation of appetite without altering either intercept or the negative quadratic function. Although mood ratings suggested that naltrexone had a mild sedative effect, mood changes alone could not explain the effects of naltrexone on appetite. Overall, these data suggest a specific role for opioids in the stimulation of appetite through palatability.",
"title": "Effects of naltrexone on food intake and changes in subjective appetite during eating: evidence for opioid involvement in the appetizer effect."
},
{
"docid": "MED-4854",
"text": "In a controlled clinical trial we have recently shown that patients with rheumatoid arthritis (RA) improved after fasting for 7-10 d and that the improvement could be sustained through 3.5 months with a vegan diet and 9 months with a lactovegetarian diet. Other studies have indicated that the inflammatory process in RA can be reduced through manipulation of dietary fatty acids. A switch to a vegetarian diet significantly alters the intake of fatty acids. Therefore, we have analysed the changes in fatty acid profiles of the plasma phospholipid fraction and related these changes to disease activity. The concentrations of the fatty acids 20:3n-6 and 20:4n-6 were significantly reduced after 3.5 months with a vegan diet (P < 0.0001 and P < 0.01 respectively), but the concentration increased to baseline values with a lactovegetarian diet. The concentration of 20:5n-3 was significantly reduced after the vegan diet (P < 0.0001) and the lactovegetarian diet periods (P < 0.01). There was no significant difference in fatty acid concentrations between diet responders and diet non-responders after the vegan or lactovegetarian diet periods. Our results indicate that the changes in the fatty acid profiles cannot explain the clinical improvement.",
"title": "Changes in plasma phospholipid fatty acids and their relationship to disease activity in rheumatoid arthritis patients treated with a vegetarian diet."
},
{
"docid": "MED-1203",
"text": "BACKGROUND: Clinical mood disorders often become clinically manifest in the later teenage years and early twenties and can be associated with a poor long-term prognosis. The primary prevention of these disorders would therefore have great public health value. Nutritional supplements are a feasible intervention for primary prevention and several epidemiological studies have indicated links between low folate status and depressive symptomatology in the general population. METHOD: A randomised, double blind, parallel group, placebo-controlled trial in which participants, aged 14-24 years, at increased familial risk of mood disorder, were randomised to folic acid (2.5 mg daily) or identical placebo liquid for a maximum of 36 months. Primary outcome data (the onset of a DSM-IV mood disorder) were collected from 112 participants; 56 per group. RESULTS: The incidence of mood disorder in the folic acid and placebo groups were 14.3% and 17.9% respectively, a non-significant difference. However, there was post-hoc evidence that folic acid delayed the time to onset of mood disorder in those participants who became unwell. LIMITATIONS: Small sample size and rate of onset of mood disorders lower than expected. CONCLUSIONS: Although long term folic acid supplementation was well tolerated, with high levels of adherence, there was no evidence that it reduced the incidence of mood disorder compared to those taking placebo. Copyright © 2014 Elsevier B.V. All rights reserved.",
"title": "Folic acid supplementation for prevention of mood disorders in young people at familial risk: a randomised, double blind, placebo controlled trial."
},
{
"docid": "MED-1524",
"text": "Ever since smoking was prohibited in restaurants, bars, and clubs, undesirable smells that were previously masked by cigarette smoke became noticeable. This opens up opportunities to improve the dance club environment by introducing pleasant ambient scents that mask the unwanted odors and to allow competing clubs to differentiate themselves. A field study was conducted at three dance clubs using a 3 × 3 Latin square design with pre- and post-measurements of no-scent control conditions. The three scents tested were orange, seawater, and peppermint. These scents were shown to enhance dancing activity and to improve the evaluation of the evening, the evaluation of the music, and the mood of the visitors over no added scent. However, no significant differences were found between the three scents.",
"title": "Can Ambient Scent Enhance the Nightlife Experience?"
},
{
"docid": "MED-4580",
"text": "Preclinical studies demonstrate that apple juice exerts multiple beneficial effects including reduction of central nervous system oxidative damage, suppression of Alzheimer's disease (AD) hallmarks, improved cognitive performance, and organized synaptic signaling. Herein, we initiated an open-label clinical trial in which 21 institutionalized individuals with moderate-to-severe AD consumed 2 4-oz glasses of apple juice daily for 1 month. Participants demonstrated no change in the Dementia Rating Scale, and institutional caregivers reported no change in Alzheimer's Disease Cooperative Study (ADCS)-Activities of Daily Living (ADL) in this brief study. However, caregivers reported an approximate 27% (P < .01) improvement in behavioral and psychotic symptoms associated with dementia as quantified by the Neuropsychiatric Inventory, with the largest changes in anxiety, agitation, and delusion. This pilot study suggests that apple juice may be a useful supplement, perhaps to augment pharmacological approaches, for attenuating the decline in mood that accompanies progression of AD, which may also reduce caregiver burden.",
"title": "Apple juice improved behavioral but not cognitive symptoms in moderate-to-late stage Alzheimer's disease in an open-label pilot study."
},
{
"docid": "MED-1348",
"text": "Background Meta-analyses of antidepressant medications have reported only modest benefits over placebo treatment, and when unpublished trial data are included, the benefit falls below accepted criteria for clinical significance. Yet, the efficacy of the antidepressants may also depend on the severity of initial depression scores. The purpose of this analysis is to establish the relation of baseline severity and antidepressant efficacy using a relevant dataset of published and unpublished clinical trials. Methods and Findings We obtained data on all clinical trials submitted to the US Food and Drug Administration (FDA) for the licensing of the four new-generation antidepressants for which full datasets were available. We then used meta-analytic techniques to assess linear and quadratic effects of initial severity on improvement scores for drug and placebo groups and on drug–placebo difference scores. Drug–placebo differences increased as a function of initial severity, rising from virtually no difference at moderate levels of initial depression to a relatively small difference for patients with very severe depression, reaching conventional criteria for clinical significance only for patients at the upper end of the very severely depressed category. Meta-regression analyses indicated that the relation of baseline severity and improvement was curvilinear in drug groups and showed a strong, negative linear component in placebo groups. Conclusions Drug–placebo differences in antidepressant efficacy increase as a function of baseline severity, but are relatively small even for severely depressed patients. The relationship between initial severity and antidepressant efficacy is attributable to decreased responsiveness to placebo among very severely depressed patients, rather than to increased responsiveness to medication. Editors' Summary Background. Everyone feels miserable occasionally. But for some people—those with depression—these sad feelings last for months or years and interfere with daily life. Depression is a serious medical illness caused by imbalances in the brain chemicals that regulate mood. It affects one in six people at some time during their life, making them feel hopeless, worthless, unmotivated, even suicidal. Doctors measure the severity of depression using the “Hamilton Rating Scale of Depression” (HRSD), a 17–21 item questionnaire. The answers to each question are given a score and a total score for the questionnaire of more than 18 indicates severe depression. Mild depression is often treated with psychotherapy or talk therapy (for example, cognitive–behavioral therapy helps people to change negative ways of thinking and behaving). For more severe depression, current treatment is usually a combination of psychotherapy and an antidepressant drug, which is hypothesized to normalize the brain chemicals that affect mood. Antidepressants include “tricyclics,” “monoamine oxidases,” and “selective serotonin reuptake inhibitors” (SSRIs). SSRIs are the newest antidepressants and include fluoxetine, venlafaxine, nefazodone, and paroxetine. Why Was This Study Done? Although the US Food and Drug Administration (FDA), the UK National Institute for Health and Clinical Excellence (NICE), and other licensing authorities have approved SSRIs for the treatment of depression, some doubts remain about their clinical efficacy. Before an antidepressant is approved for use in patients, it must undergo clinical trials that compare its ability to improve the HRSD scores of patients with that of a placebo, a dummy tablet that contains no drug. Each individual trial provides some information about the new drug's effectiveness but additional information can be gained by combining the results of all the trials in a “meta-analysis,” a statistical method for combining the results of many studies. A previously published meta-analysis of the published and unpublished trials on SSRIs submitted to the FDA during licensing has indicated that these drugs have only a marginal clinical benefit. On average, the SSRIs improved the HRSD score of patients by 1.8 points more than the placebo, whereas NICE has defined a significant clinical benefit for antidepressants as a drug–placebo difference in the improvement of the HRSD score of 3 points. However, average improvement scores may obscure beneficial effects between different groups of patient, so in the meta-analysis in this paper, the researchers investigated whether the baseline severity of depression affects antidepressant efficacy. What Did the Researchers Do and Find? The researchers obtained data on all the clinical trials submitted to the FDA for the licensing of fluoxetine, venlafaxine, nefazodone, and paroxetine. They then used meta-analytic techniques to investigate whether the initial severity of depression affected the HRSD improvement scores for the drug and placebo groups in these trials. They confirmed first that the overall effect of these new generation of antidepressants was below the recommended criteria for clinical significance. Then they showed that there was virtually no difference in the improvement scores for drug and placebo in patients with moderate depression and only a small and clinically insignificant difference among patients with very severe depression. The difference in improvement between the antidepressant and placebo reached clinical significance, however, in patients with initial HRSD scores of more than 28—that is, in the most severely depressed patients. Additional analyses indicated that the apparent clinical effectiveness of the antidepressants among these most severely depressed patients reflected a decreased responsiveness to placebo rather than an increased responsiveness to antidepressants. What Do These Findings Mean? These findings suggest that, compared with placebo, the new-generation antidepressants do not produce clinically significant improvements in depression in patients who initially have moderate or even very severe depression, but show significant effects only in the most severely depressed patients. The findings also show that the effect for these patients seems to be due to decreased responsiveness to placebo, rather than increased responsiveness to medication. Given these results, the researchers conclude that there is little reason to prescribe new-generation antidepressant medications to any but the most severely depressed patients unless alternative treatments have been ineffective. In addition, the finding that extremely depressed patients are less responsive to placebo than less severely depressed patients but have similar responses to antidepressants is a potentially important insight into how patients with depression respond to antidepressants and placebos that should be investigated further. Additional Information. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050045.",
"title": "Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration"
},
{
"docid": "MED-823",
"text": "While lifestyle management is recommended as first-line treatment of polycystic ovary syndrome (PCOS), the optimal dietary composition is unclear. The aim of this study was to compare the effect of different diet compositions on anthropometric, reproductive, metabolic, and psychological outcomes in PCOS. A literature search was conducted (Australasian Medical Index, CINAHL, EMBASE, Medline, PsycInfo, and EBM reviews; most recent search was performed January 19, 2012). Inclusion criteria were women with PCOS not taking anti-obesity medications and all weight-loss or maintenance diets comparing different dietary compositions. Studies were assessed for risk of bias. A total of 4,154 articles were retrieved and six articles from five studies met the a priori selection criteria, with 137 women included. A meta-analysis was not performed due to clinical heterogeneity for factors including participants, dietary intervention composition, duration, and outcomes. There were subtle differences between diets, with greater weight loss for a monounsaturated fat-enriched diet; improved menstrual regularity for a low-glycemic index diet; increased free androgen index for a high-carbohydrate diet; greater reductions in insulin resistance, fibrinogen, total, and high-density lipoprotein cholesterol for a low-carbohydrate or low-glycemic index diet; improved quality of life for a low-glycemic index diet; and improved depression and self-esteem for a high-protein diet. Weight loss improved the presentation of PCOS regardless of dietary composition in the majority of studies. Weight loss should be targeted in all overweight women with PCOS through reducing caloric intake in the setting of adequate nutritional intake and healthy food choices irrespective of diet composition. Copyright © 2013 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.",
"title": "Dietary composition in the treatment of polycystic ovary syndrome: a systematic review to inform evidence-based guidelines."
},
{
"docid": "MED-2441",
"text": "Many patients with atopic dermatitis are dissatisfied with conventional treatments based on topical steroids and have experienced some traditional remedies and alternative therapies. However, most of such therapies have not been evaluated scientifically and clinically by specialists. This study was designed to assess whether a certain vegetarian diet might be effective for atopic dermatitis and if so, to identify the mechanisms of this remedy through analyses of immunological parameters. An open-trial study was carried out in twenty patients with atopic dermatitis. An improvement of dermatitis was evaluated by SCORAD index and serological and immunological parameters were monitored. After a two-month treatment, the severity of dermatitis was strikingly inhibited, as assessed by SCORAD index and serological parameters including LDH5 activity and a number of peripheral eosinophils. A sharp reduction in eosinophils and neutrophils was observed prior to improvement in the skin inflammation. In addition, PGE2 production by peripheral blood mononuclear cells was reduced by this treatment. In contrast, serum IgE levels did not change during the same period. Although this study is an open-trial one, it suggests that this treatment may be useful for the treatment of adult patients with severe atopic dermatitis.",
"title": "Vegetarian diet ameliorates symptoms of atopic dermatitis through reduction of the number of peripheral eosinophils and of PGE2 synthesis by monocy..."
},
{
"docid": "MED-1358",
"text": "This paper documents the recent (1976-1995) literature on the acute mood effects associated with participation in single sessions of exercise. Issues regarding experimental design, \"ecological validity' and the operational definition of mood are addressed. Results from these studies suggest that both clinical and nonclinical subjects may benefit acutely from even a single bout of exercise. Finally, possible mechanisms and recommendations for future research are discussed.",
"title": "The acute effects of exercise on mood state."
},
{
"docid": "MED-5367",
"text": "Objective We examined the cross-sectional and longitudinal relationship between plasma carotenoids and depressive symptoms over a six-year follow-up in older persons. Methods and Materials This research is part of the InCHIANTI Study, a prospective population-based study of older persons in Tuscany, Italy. The sample for this analysis included 958 women and men aged 65 years and older. Plasma total carotenoids were assessed at baseline. Depressive symptoms were assessed at baseline and at the 3- and 6-year follow-up using the Center for Epidemiological Studies-Depression Scale (CES-D). Depressed mood was defined as CES-D≥20. Results At baseline, higher total carotenoids level were associated with lower probability of depressed mood (OR=0.82, 95%CI=0.68–0.99, p=0.04) after adjustment for sociodemographic, health and inflammation. After the exclusion of participants with baseline depressed mood and use of antidepressants, higher total carotenoids level were associated with lower risk of incident depressed mood (OR=0.72, 95%CI=0.52–0.99, p=0.04) at 6-year follow-up, after adjustment for confounders plus baseline CES-D. Inflammatory marker Interleukin-1 receptor antagonist partially mediated this association. Discussion Low plasma concentrations of carotenoids are associated with depressive symptoms and predict the development of new depressive symptoms in older persons. Understanding the mechanism of this association may reveal potential targets for prevention and treatment.",
"title": "The relationship between plasma carotenoids and depressive symptoms in older persons"
},
{
"docid": "MED-3673",
"text": "Chronic fatigue syndrome (CFS) is a debilitating disease characterized by unexplained disabling fatigue and a combination of accompanying symptoms the pathology of which is incompletely understood. Many CFS patients complain of gut dysfunction. In fact, patients with CFS are more likely to report a previous diagnosis of irritable bowel syndrome (IBS), a common functional disorder of the gut, and experience IBS-related symptoms. Recently, evidence for interactions between the intestinal microbiota, mucosal barrier function, and the immune system have been shown to play a role in the disorder's pathogenesis. Studies examining the microecology of the gastrointestinal (GI) tract have identified specific microorganisms whose presence appears related to disease; in CFS, a role for altered intestinal microbiota in the pathogenesis of the disease has recently been suggested. Mucosal barrier dysfunction promoting bacterial translocation has also been observed. Finally, an altered mucosal immune system has been associated with the disease. In this article, we discuss the interplay between these factors in CFS and how they could play a significant role in GI dysfunction by modulating the activity of the enteric nervous system, the intrinsic innervation of the gut. If an altered intestinal microbiota, mucosal barrier dysfunction, and aberrant intestinal immunity contribute to the pathogenesis of CFS, therapeutic efforts to modify gut microbiota could be a means to modulate the development and/or progression of this disorder. For example, the administration of probiotics could alter the gut microbiota, improve mucosal barrier function, decrease pro-inflammatory cytokines, and have the potential to positively influence mood in patients where both emotional symptoms and inflammatory immune signals are elevated. Probiotics also have the potential to improve gut motility, which is dysfunctional in many CFS patients.",
"title": "Gut inflammation in chronic fatigue syndrome"
},
{
"docid": "MED-2710",
"text": "A systematic review of scientific experimentation addressing olfactory effects on mood, physiology and behavior was undertaken. From this review, 18 studies meeting stringent empirical criteria were then analyzed in detail and it was found that credible evidence that odors can affect mood, physiology and behavior exists. To explain these effects, pharmacological and psychological mechanisms were explored and a psychological interpretation of the data was found to be more comprehensive. Methodological problems regarding dependent measures and stimuli, which led to inconsistencies in the data were discussed, as were the mediating variables of culture, experience, sex differences, and personality.",
"title": "Aromatherapy facts and fictions: a scientific analysis of olfactory effects on mood, physiology and behavior."
},
{
"docid": "MED-3668",
"text": "OBJECTIVE: Investigate the effects of lavender oil on the central nervous system, autonomic nervous system, and mood responses in humans after inhalation. MATERIAL AND METHOD: Twenty healthy volunteers participated in the experiments. The present study assessed autonomic parameters such as blood pressure, heart rate, respiratory rate, and skin temperature to determine the arousal level of the autonomic nervous system. In addition, subjects were asked to estimate their mood responses such as feeling pleasant or unpleasant, uncomfortable, sensuality, relaxation, or refreshing in order to assess subjective behavioral arousal. Finally, electroencephalogram (EEG) was recorded from 31 electrodes on the scalp according to the international 10 to 20 system, and EEG power spectra were calculated by Fast Fourier Transform (FFT). Data was analyzed by comparing the effects of lavender oil on physiological and mood states with sweet almond oil. These assessments were measured before and after using paired t-test statistical procedure. RESULTS: The results revealed that lavender oil caused significant decreases of blood pressure, heart rate, and skin temperature, which indicated a decrease of autonomic arousal. In terms of mood responses, the subjects in the lavender oil group categorized themselves as more active, fresher relaxed than subjects just inhaling base oil. Compared with base oil, lavender oil increased the power of theta (4-8 Hz) and alpha (8-13 Hz) brain activities. The topographic map showed obviously more scattering power in alpha range waves particularly in bilateral temporal and central area. CONCLUSION: The findings provided evidence the relaxing effect of inhaling lavender oil.",
"title": "The effects of lavender oil inhalation on emotional states, autonomic nervous system, and brain electrical activity."
},
{
"docid": "MED-4848",
"text": "We have previously reported that a significant improvement can be obtained in rheumatoid arthritis patients by fasting followed by an individually adjusted vegetarian diet for one year. The patients who changed their diet could be divided into diet responders and diet nonresponders. After the clinical trial the patients were free to change diet or medication and after approximately one year they were asked to attend a new clinical examination. We compared the change from baseline (i.e. at the time of study entry) to the time of the follow-up examination for diet responders, diet nonresponders and controls who ate an omnivorous diet. The following variables favoured diet responders: pain score, duration of morning stiffness, Stanford Health Assessment Questionnaire index, number of tender joints, Ritchie's articular index, number of swollen joints, ESR and platelet count [corrected]. The difference between the three groups were significant for all the clinical variables, except for grip strength. There was no significant difference between the groups with regard to laboratory or anthropometric variables. At the time of the follow-up examination all diet responders but only half of the diet nonresponders still followed a diet. Our findings indicate that a group of patients with rheumatoid arthritis benefit from dietary manipulations and that the improvement can be sustained through a two-year period.",
"title": "Vegetarian diet for patients with rheumatoid arthritis--status: two years after introduction of the diet."
},
{
"docid": "MED-825",
"text": "BACKGROUND: Some evidence has suggested that a diet with a higher ratio of protein to carbohydrates has metabolic advantages in the treatment of polycystic ovary syndrome (PCOS). OBJECTIVE: The objective of this study was to compare the effect of a high-protein (HP) diet to a standard-protein (SP) diet in women with PCOS. DESIGN: A controlled, 6-mo trial was conducted in 57 PCOS women. The women were assigned through rank minimization to one of the following 2 diets without caloric restriction: an HP diet (>40% of energy from protein and 30% of energy from fat) or an SP diet (<15% of energy from protein and 30% of energy from fat). The women received monthly dietary counseling. At baseline and 3 and 6 mo, anthropometric measurements were performed, and blood samples were collected. RESULTS: Seven women dropped out because of pregnancy, 23 women dropped out because of other reasons, and 27 women completed the study. The HP diet produced a greater weight loss (mean: 4.4 kg; 95% CI: 0.3, 8.6 kg) and body fat loss (mean: 4.3 kg; 95% CI: 0.9, 7.6 kg) than the SP diet after 6 mo. Waist circumference was reduced more by the HP diet than by the SP diet. The HP diet produced greater decreases in glucose than did the SP diet, which persisted after adjustment for weight changes. There were no differences in testosterone, sex hormone-binding globulin, and blood lipids between the groups after 6 mo. However, adjustment for weight changes led to significantly lower testosterone concentrations in the SP-diet group than in the HP-diet group. CONCLUSION: Replacement of carbohydrates with protein in ad libitum diets improves weight loss and improves glucose metabolism by an effect that seems to be independent of the weight loss and, thus, seems to offer an improved dietary treatment of PCOS women.",
"title": "Effects of increased dietary protein-to-carbohydrate ratios in women with polycystic ovary syndrome."
},
{
"docid": "MED-3669",
"text": "EEG activity, alertness, and mood were assessed in 40 adults given 3 minutes of aromatherapy using two aromas, lavender (considered a relaxing odor) or rosemary (considered a stimulating odor). Participants were also given simple math computations before and after the therapy. The lavender group showed increased beta power, suggesting increased drowsiness, they had less depressed mood (POMS) and reported feeling more relaxed and performed the math computations faster and more accurately following aromatherapy. The rosemary group, on the other hand, showed decreased frontal alpha and beta power, suggesting increased alertness. They also had lower state anxiety scores, reported feeling more relaxed and alert and they were only faster, not more accurate, at completing the math computations after the aromatherapy session.",
"title": "Aromatherapy positively affects mood, EEG patterns of alertness and math computations."
},
{
"docid": "MED-2527",
"text": "BACKGROUND: One of the major issues in controlling serum cholesterol through dietetic intervention appears to be the need to improve patient adherence. AIMS: To explore the many questions regarding barriers to, and motivators for, cholesterol-lowering diet adherence. METHODS: We surveyed French general practitioners' dietetic practices for patients with hypercholesterolaemia, and looked at their patients' attitudes towards such an approach. RESULTS: We analysed 234 doctors' personal questionnaires and 356 patient self-survey questionnaires. Patients' reasons for not complying with the prescribed diet included: 'already having satisfactory food habits' (34.7%), 'unwillingness to suffer nutritional deprivation' (33.3%), 'difficulties to conciliate a diet with family life' (27.8%) and 'taking cholesterol-lowering drugs' (22.2%). Despite a generally good understanding by patients of doctors' recommendations, some discrepancies were seen between their respective declarations. While doctors largely thought that patients needed more explanation on why and how a diet can lower cholesterol (and avoid taking drugs), only 39.4% of patients declared needing this kind of information. Other discrepancies were observed concerning barriers to, and motivators for, patient adherence. Moreover, some dietetic rules appeared to be more difficult to comply with than others, e.g. 82.6% patients remembered they should 'eat more fish' but only 51.3% actually did so. Finally, physicians, as well as patients, displayed a lack of confidence in lipid-lowering diet efficiency. CONCLUSION: Improving patient education, especially concerning their perception of risk, as well as increasing the involvement of dieticians, are motivators to explore in order to improve adherence. Copyright © 2012 Elsevier Masson SAS. All rights reserved.",
"title": "Cross-analysis of dietary prescriptions and adherence in 356 hypercholesterolaemic patients."
},
{
"docid": "MED-3675",
"text": "Chronic fatigue syndrome (CFS) is complex illness of unknown etiology. Among the broad range of symptoms, many patients report disturbances in the emotional realm, the most frequent of which is anxiety. Research shows that patients with CFS and other so-called functional somatic disorders have alterations in the intestinal microbial flora. Emerging studies have suggested that pathogenic and non-pathogenic gut bacteria might influence mood-related symptoms and even behavior in animals and humans. In this pilot study, 39 CFS patients were randomized to receive either 24 billion colony forming units of Lactobacillus casei strain Shirota (LcS) or a placebo daily for two months. Patients provided stool samples and completed the Beck Depression and Beck Anxiety Inventories before and after the intervention. We found a significant rise in both Lactobacillus and Bifidobacteria in those taking the LcS, and there was also a significant decrease in anxiety symptoms among those taking the probiotic vs controls (p = 0.01). These results lend further support to the presence of a gut-brain interface, one that may be mediated by microbes that reside or pass through the intestinal tract.",
"title": "A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome"
}
] |
930
|
Patients with panic anxiety show decreased CSF levels of hypocretin.
|
[
{
"docid": "16056514",
"text": "Panic disorder is a severe anxiety disorder with recurrent, debilitating panic attacks. In individuals with panic disorder there is evidence of decreased central gamma-aminobutyric acid (GABA) activity as well as marked increases in autonomic and respiratory responses after intravenous infusions of hypertonic sodium lactate. In a rat model of panic disorder, chronic inhibition of GABA synthesis in the dorsomedial-perifornical hypothalamus of rats produces anxiety-like states and a similar vulnerability to sodium lactate-induced cardioexcitatory responses. The dorsomedial-perifornical hypothalamus is enriched in neurons containing orexin (ORX, also known as hypocretin), which have a crucial role in arousal, vigilance and central autonomic mobilization, all of which are key components of panic. Here we show that activation of ORX-synthesizing neurons is necessary for developing a panic-prone state in the rat panic model, and either silencing of the hypothalamic gene encoding ORX (Hcrt) with RNAi or systemic ORX-1 receptor antagonists blocks the panic responses. Moreover, we show that human subjects with panic anxiety have elevated levels of ORX in the cerebrospinal fluid compared to subjects without panic anxiety. Taken together, our results suggest that the ORX system may be involved in the pathophysiology of panic anxiety and that ORX antagonists constitute a potential new treatment strategy for panic disorder.",
"title": "A KEY ROLE FOR OREXIN IN PANIC ANXIETY"
}
] |
[
{
"docid": "44830890",
"text": "OBJECTIVE To investigate the frequency of depressive and anxiety disorders in patients with chronic daily headache. BACKGROUND There is a lack of data in the literature on the extent of psychiatric comorbidity in patients with different subtypes of chronic daily headache. METHODS We recruited consecutive patients with chronic daily headache seen in a headache clinic from November 1998 to December 1999. The subtypes of chronic daily headache were classified according to the criteria proposed by Silberstein et al. A psychiatrist evaluated the patients according to the structured Mini-International Neuropsychiatric Interview to assess the comorbidity of depressive and anxiety disorders. RESULTS Two hundred sixty-one patients with chronic daily headache were recruited. The mean age was 46 years, and 80% were women. Transformed migraine was diagnosed in 152 patients (58%) and chronic tension-type headache in 92 patients (35%). Seventy-eight percent of patients with transformed migraine had psychiatric comorbidity, including major depression (57%), dysthymia (11%), panic disorder (30%), and generalized anxiety disorder (8%). Sixty-four percent of patients with chronic tension-type headache had psychiatric diagnoses, including major depression (51%), dysthymia (8%), panic disorder (22%), and generalized anxiety disorder (1%). The frequency of anxiety disorders was significantly higher in patients with transformed migraine after controlling for age and sex (P =.02). Both depressive and anxiety disorders were significantly more frequent in women. CONCLUSION Psychiatric comorbidity, especially major depression and panic disorders, was highly prevalent in patients with chronic daily headache seen in a headache clinic. These results demonstrate that women and patients with transformed migraine are at higher risk of psychiatric comorbidity.",
"title": "Comorbidity of depressive and anxiety disorders in chronic daily headache and its subtypes."
},
{
"docid": "52874170",
"text": "CONTEXT Diagnostic lumbar punctures (LPs), commonly used to rule out meningitis, are associated with adverse events. OBJECTIVE To systematically review the evidence about diagnostic LP techniques that may decrease the risk of adverse events and the evidence about test accuracy of cerebrospinal fluid (CSF) analysis in adult patients with suspected bacterial meningitis. DATA SOURCES We searched the Cochrane Library, MEDLINE (using Ovid and PubMed) from 1966 to January 2006 and EMBASE from 1980 to January 2006 without language restrictions to identify relevant studies and identified others from the bibliographies of retrieved articles. STUDY SELECTION We included randomized trials of patients aged 18 years or older undergoing interventions to facilitate a successful diagnostic LP or to potentially reduce adverse events. Studies assessing the accuracy of biochemical analysis of the CSF for possible bacterial meningitis were also identified. DATA EXTRACTION Two investigators independently appraised study quality and extracted relevant data. For studies of the LP technique, data on the intervention and the outcome were extracted. For studies of the laboratory diagnosis of bacterial meningitis, data on the reference standard and test accuracy were extracted. DATA SYNTHESIS We found 15 randomized trials. A random-effects model was used for quantitative synthesis. Five studies of 587 patients compared atraumatic needles with standard needles and found a nonsignificant decrease in the odds of headache with an atraumatic needle (absolute risk reduction [ARR], 12.3%; 95% confidence interval [CI], -1.72% to 26.2%). Reinsertion of the stylet before needle removal decreased the risk of headache (ARR, 11.3%; 95% CI, 6.50%-16.2%). The combined results from 4 studies of 717 patients showed a nonsignificant decrease in headache in patients who were mobilized after LP (ARR, 2.9%; 95% CI, -3.4 to 9.3%). Four studies on the accuracy of biochemical analysis of CSF in patients with suspected meningitis met inclusion criteria. A CSF-blood glucose ratio of 0.4 or less (likelihood ratio [LR], 18; 95% CI, 12-27]), CSF white blood cell count of 500/muL or higher (LR, 15; 95% CI, 10-22), and CSF lactate level of 31.53 mg/dL or more (> or =3.5 mmol/L; LR, 21; 95% CI, 14-32) accurately diagnosed bacterial meningitis. CONCLUSIONS These data suggest that small-gauge, atraumatic needles may decrease the risk of headache after diagnostic LP. Reinsertion of the stylet before needle removal should occur and patients do not require bed rest after the procedure. Future research should focus on evaluating interventions to optimize the success of a diagnostic LP and to enhance training in procedural skills.",
"title": "How do I perform a lumbar puncture and analyze the results to diagnose bacterial meningitis?"
},
{
"docid": "24770122",
"text": "To assess the clinical and personality characteristics of patients with chronic daily headache before and after treatment, 20 patients were examined and the Minnesota Multiphasic Personality Inventory (MMPI [Italian 356-item abbreviated version]) and the Strait and Trait Anxiety Index 1,2 (STAI) administered. There were two groups: group 1 (n = 6), with a \"conversion V\" configuration (with elevation of hypochondria and hysteria scales, the depression scale being somewhat lower); and group 2 (n = 13) with elevation of depression and of other MMPI scales. One patient had no scale elevation. STAI 1,2 scores were high in both groups. Several psychosomatic symptoms and some migraine features were present in almost all patients. Occurrence, severity, and duration of headache were recorded regularly and the MMPI and the STAI administered again after treatment. Improvement of headaches and a decrease of several MMPI and STAI 2 scores were observed. However, 12 of 20 patients showed a conversion V configuration after treatment. It is concluded that chronic daily headache was transformed migraine in most cases and was accompanied by anxiety levels in all patients and hysteric traits in some. With time, these patients may develop a depressive disorder. After treatment, hysterical traits are still present at a lower level in those showing these traits before treatment and may be unmasked in those that had depression.",
"title": "Chronic daily headache. A clinical and psychological profile before and after treatment."
},
{
"docid": "36721932",
"text": "OBJECTIVE Nociceptive and neuropathic components both contribute to pain. Since these components require different pain management strategies, correct pain diagnosis before and during treatment is highly desirable. As low back pain (LBP) patients constitute an important subgroup of chronic pain patients, we addressed the following issues: (i) to establish a simple, validated screening tool to detect neuropathic pain (NeP) components in chronic LBP patients, (ii) to determine the prevalence of neuropathic pain components in LBP in a large-scale survey, and (iii) to determine whether LBP patients with an NeP component suffer from worse, or different, co-morbidities. METHODS In co-operation with the German Research Network on Neuropathic Pain we developed and validated the painDETECT questionnaire (PD-Q) in a prospective, multicentre study and subsequently applied it to approximately 8000 LBP patients. RESULTS The PD-Q is a reliable screening tool with high sensitivity, specificity and positive predictive accuracy; these were 84% in a palm-top computerised version and 85%, 80% and 83%, respectively, in a corresponding pencil-and-paper questionnaire. In an unselected cohort of chronic LBP patients, 37% were found to have predominantly neuropathic pain. Patients with NeP showed higher ratings of pain intensity, with more (and more severe) co-morbidities such as depression, panic/anxiety and sleep disorders. This also affected functionality and use of health-care resources. On the basis of given prevalence of LBP in the general population, we calculated that 14.5% of all female and 11.4% of all male Germans suffer from LBP with a predominant neuropathic pain component. CONCLUSION Simple, patient-based, easy-to-use screening questionnaires can determine the prevalence of neuropathic pain components both in individual LBP patients and in heterogeneous cohorts of such patients. Since NeP correlates with more intense pain, more severe co-morbidity and poorer quality of life, accurate diagnosis is a milestone in choosing appropriate therapy.",
"title": "painDETECT: a new screening questionnaire to identify neuropathic components in patients with back pain."
},
{
"docid": "27024392",
"text": "Cannabis has a potential for clinical use often obscured by unreliable and purely anecdotal reports. The most important natural cannabinoid is the psychoactive tetrahydrocannabinol (Δ9-THC); others include cannabidiol (CBD) and cannabigerol (CBG). Not all the observed effects can be ascribed to THC, and the other constituents may also modulate its action; for example CBD reduces anxiety induced by THC. A standardised extract of the herb may be therefore be more beneficial in practice and clinical trial protocols have been drawn up to assess this. The mechanism of action is still not fully understood, although cannabinoid receptors have been cloned and natural ligands identified. Cannabis is frequently used by patients with multiple sclerosis (MS) for muscle spasm and pain, and in an experimental model of MS low doses of cannabinoids alleviated tremor. Most of the controlled studies have been carried out with THC rather than cannabis herb and so do not mimic the usual clincal situation. Small clinical studies have confirmed the usefulness of THC as an analgesic; CBD and CBG also have analgesic and antiinflammatory effects, indicating that there is scope for developing drugs which do not have the psychoactive properties ofTHC. Patients taking the synthetic derivative nabilone for neurogenic pain actually preferred cannabis herb and reported that it relieved not only pain but the associated depression and anxiety. Cannabinoids are effective in chemotherapy-induced emesis and nabilone has been licensed for this use for several years. Currently, the synthetic cannabinoid HU211 is undergoing trials as a protective agent after brain trauma. Anecdotal reports of cannabis use include case studies in migraine and Tourette’s syndrome, and as a treatment for asthma and glaucoma. Apart from the smoking aspect, the safety profile of cannabis is fairly good. However, adverse reactions include panic or anxiety attacks, which are worse in the elderly and in women, and less likely in children. Although psychosis has been cited as a consequence of cannabis use, an examination of psychiatric hospital admissions found no evidence of this, however, it may exacerbate existing symptoms. The relatively slow elimination from the body of the cannabinoids has safety implications for cognitive tasks, especially driving and operating machinery; although driving impairment with cannabis is only moderate, there is a significant interaction with alcohol. Natural materials are highly variable and multiple components need to be standardised to ensure reproducible effects. Pure natural and synthetic compounds do not have these disadvantages but may not have the overall therapeutic effect of the herb.",
"title": "Cannabinoids in Clinical Practice"
},
{
"docid": "654735",
"text": "Glioma is a most common type of primary brain tumors. Extracellular vesicles, in the form of exosomes, are known to mediate cell-cell communication by transporting cell-derived proteins and nucleic acids, including various microRNAs (miRNAs). Here we examined the cerebrospinal fluid (CSF) from patients with recurrent glioma for the levels of cancer-related miRNAs, and evaluated the values for prognosis by comparing the measures of CSF-, serum-, and exosome-contained miR-21 levels. Samples from seventy glioma patients following surgery were compared with those from brain trauma patients as a non-tumor control group. Exosomal miR-21 levels in the CSF of glioma patients were found significantly higher than in the controls; whereas no difference was detected in serum-derived exosomal miR-21 expression. The CSF-derived exosomal miR-21 levels correlated with tumor spinal/ventricle metastasis and the recurrence with anatomical site preference. From additional 198 glioma tissue samples, we verified that miR-21 levels associated with tumor grade of diagnosis and negatively correlated with the median values of patient overall survival time. We further used a lentiviral inhibitor to suppress miR-21 expression in U251 cells. The results showed that the levels of miR-21 target genes of PTEN, RECK and PDCD4 were up-regulated at protein levels. Therefore, we concluded that the exosomal miR-21 levels could be demonstrated as a promising indicator for glioma diagnosis and prognosis, particularly with values to predict tumor recurrence or metastasis.",
"title": "Exosomal levels of miRNA-21 from cerebrospinal fluids associated with poor prognosis and tumor recurrence of glioma patients"
},
{
"docid": "5260382",
"text": "Serotonin signaling suppresses generation of amyloid-β (Aβ) in vitro and in animal models of Alzheimer’s disease (AD). We show that in an aged transgenic AD mouse model (APP/PS1 plaque-bearing mice), the antidepressant citalopram, a selective serotonin reuptake inhibitor, decreased Aβ in brain interstitial fluid in a dose-dependent manner. Growth of individual amyloid plaques was assessed in plaque-bearing mice that were chronically administered citalopram. Citalopram arrested the growth of preexisting plaques and reduced the appearance of new plaques by 78%. In healthy human volunteers, citalopram’s effects on Aβ production and Aβ concentrations in cerebrospinal fluid (CSF) were measured prospectively using stable isotope labeling kinetics, with CSF sampling during acute dosing of citalopram. Aβ production in CSF was slowed by 37% in the citalopram group compared to placebo. This change was associated with a 38% decrease in total CSF Aβ concentrations in the drug-treated group. The ability to safely decrease Aβ concentrations is potentially important as a preventive strategy for AD. This study demonstrates key target engagement for future AD prevention trials.",
"title": "An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice"
},
{
"docid": "25440070",
"text": "Testosterone (T) and its 5alpha-reduced metabolite, dihydrotestosterone (DHT), can decrease anxiety-like behavior; however, the mechanisms underlying these effects have not been established. First, we hypothesized that if T reduces anxiety-like behavior through actions of its 5alpha-reduced metabolite, DHT, then gonadectomy (GDX) would increase anxiety-like behavior, an effect which would be reversed by systemic administration of DHT. Second, we hypothesized that if T and DHT reduce anxiety-like behavior in part through actions at intracellular androgen receptors in the hippocampus, then administration of an androgen receptor antagonist, flutamide, directly to the hippocampus should increase anxiety-like behavior of intact and DHT-replaced, but not GDX, male rats. Inserts that were empty or contained flutamide were applied directly to the dorsal hippocampus of intact, GDX, or GDX and DHT-replaced rats 2 h prior to testing in the open field, elevated plus maze, or defensive freezing tasks. GDX rats exhibited significantly more anxiety-like behaviors than intact or DHT-replaced rats. Intact and DHT-replaced rats administered flutamide to the hippocampus showed significantly more anxiety-like behavior than did intact and DHT-replaced controls. However, flutamide alone did not increase anxiety-like behavior of GDX rats. Together, these findings suggest that androgens can decrease anxiety-like behavior of male rats in part through DHT's actions at androgen receptors in the hippocampus.",
"title": "Intrahippocampal administration of an androgen receptor antagonist, flutamide, can increase anxiety-like behavior in intact and DHT-replaced male rats."
},
{
"docid": "46565020",
"text": "BACKGROUND AN1792 (beta-amyloid [Abeta]1-42) immunization reduces Abeta plaque burden and preserves cognitive function in APP transgenic mice. The authors report the results of a phase IIa immunotherapy trial of AN1792(QS-21) in patients with mild to moderate Alzheimer disease (AD) that was interrupted because of meningoencephalitis in 6% of immunized patients. METHODS This randomized, multicenter, placebo-controlled, double-blind trial of IM AN1792 225 microg plus the adjuvant QS-21 50 microg (300 patients) and saline (72 patients) included patients aged 50 to 85 years with probable AD, Mini-Mental State Examination (MMSE) 15 to 26. Injections were planned for months 0, 1, 3, 6, 9, and 12. Safety and tolerability were evaluated, and pilot efficacy (AD Assessment Scale-Cognitive Subscale [ADAS-Cog], MRI, neuropsychological test battery [NTB], CSF tau, and Abeta42) was assessed in anti-AN1792 antibody responder patients (immunoglobulin G titer > or = 1:2,200). RESULTS Following reports of meningoencephalitis (overall 18/300 [6%]), immunization was stopped after one (2 patients), two (274 patients), or three (24 patients) injections. Of the 300 AN1792(QS-21)-treated patients, 59 (19.7%) developed the predetermined antibody response. Double-blind assessments were maintained for 12 months. No significant differences were found between antibody responder and placebo groups for ADAS-Cog, Disability Assessment for Dementia, Clinical Dementia Rating, MMSE, or Clinical Global Impression of Change, but analyses of the z-score composite across the NTB revealed differences favoring antibody responders (0.03 +/- 0.37 vs -0.20 +/- 0.45; p = 0.020). In the small subset of subjects who had CSF examinations, CSF tau was decreased in antibody responders (n = 11) vs placebo subjects (n = 10; p < 0.001). CONCLUSION Although interrupted, this trial provides an indication that Abeta immunotherapy may be useful in Alzheimer disease.",
"title": "Clinical effects of Abeta immunization (AN1792) in patients with AD in an interrupted trial."
},
{
"docid": "3943235",
"text": "During physiological or psychological stress, catecholamines produced by the sympathetic nervous system (SNS) regulate the immune system. Previous studies report that the activation of β-adrenergic receptors (βARs) mediates the actions of catecholamines and increases pro-inflammatory cytokine production in a number of different cell types. The impact of the SNS on the immune modulation of social defeat has not been examined. The following studies were designed to determine whether SNS activation during social disruption stress (SDR) influences anxiety-like behavior as well as the activation, priming, and glucocorticoid resistance of splenocytes after social stress. CD-1 mice were exposed to one, three, or six cycles of SDR and HPLC analysis of the plasma and spleen revealed an increase in catecholamines. After six cycles of SDR the open field test was used to measure behaviors characteristic of anxiety and indicated that the social defeat induced increase in anxiety-like behavior was blocked by pre-treatment with the β-adrenergic antagonist propranolol. Pre-treatment with the β-adrenergic antagonist propranolol did not significantly alter corticosterone levels indicating no difference in activation of the hypothalamic-pituitary-adrenal axis. In addition to anxiety-like behavior the SDR induced splenomegaly and increase in plasma IL-6, TNFα, and MCP-1 were each reversed by pre-treatment with propranolol. Furthermore, flow cytometric analysis of cells from propranolol pretreated mice reduced the SDR-induced increase in the percentage of CD11b(+) splenic macrophages and significantly decreased the expression of TLR2, TLR4, and CD86 on the surface of these cells. In addition, supernatants from 18h LPS-stimulated ex vivo cultures of splenocytes from propranolol-treated SDR mice contained less IL-6. Likewise propranolol pre-treatment abrogated the glucocorticoid insensitivity of CD11b(+) cells ex vivo when compared to splenocytes from SDR vehicle-treated mice. Together, this study demonstrates that the immune activation and priming effects of SDR result, in part, as a consequence of SNS activation.",
"title": "Beta adrenergic blockade decreases the immunomodulatory effects of social disruption stress"
},
{
"docid": "10207180",
"text": "INTRODUCTION The β-secretase enzyme, β-site amyloid precursor protein-cleaving enzyme 1 (BACE1), cleaves amyloid precursor protein (APP) in the first step in β-amyloid (Aβ) peptide production. Thus, BACE1 is a key target for candidate disease-modifying treatment of Alzheimer's disease. In a previous exploratory Aβ biomarker study, we found that BACE1 inhibitor treatment resulted in decreased levels of Aβ1-34 together with increased Aβ5-40, suggesting that these Aβ species may be novel pharmacodynamic biomarkers in clinical trials. We have now examined whether the same holds true in humans. METHODS In an investigator-blind, placebo-controlled and randomized study, healthy subjects (n =18) were randomly assigned to receive a single dose of 30 mg of LY2811376 (n =6), 90 mg of LY2811376 (n =6), or placebo (n =6). We used hybrid immunoaffinity-mass spectrometry (HI-MS) and enzyme-linked immunosorbent assays to monitor a variety of Aβ peptides. RESULTS Here, we demonstrate dose-dependent changes in cerebrospinal fluid (CSF) Aβ1-34, Aβ5-40 and Aβ5-X after treatment with the BACE1-inhibitor LY2811376. Aβ5-40 and Aβ5-X increased dose-dependently, as reflected by two independent methods, while Aβ1-34 dose-dependently decreased. CONCLUSION Using HI-MS for the first time in a study where subjects have been treated with a BACE inhibitor, we confirm that CSF Aβ1-34 may be useful in clinical trials on BACE1 inhibitors to monitor target engagement. Since it is less hydrophobic than longer Aβ species, it is less susceptible to preanalytical confounding factors and may thus be a more stable marker. By independent measurement techniques, we also show that BACE1 inhibition in humans is associated with APP-processing into N-terminally truncated Aβ peptides via a BACE1-independent pathway. TRIAL REGISTRATION ClinicalTrials.gov NCT00838084. Registered: First received: January 23, 2009, Last updated: July 14, 2009, Last verified: July 2009.",
"title": "β-site amyloid precursor protein-cleaving enzyme 1(BACE1) inhibitor treatment induces Aβ5-X peptides through alternative amyloid precursor protein cleavage"
},
{
"docid": "2436602",
"text": "Psychosocial stress is associated with altered immune function and development of psychological disorders including anxiety and depression. Here we show that repeated social defeat in mice increased c-Fos staining in brain regions associated with fear and threat appraisal and promoted anxiety-like behavior in a β-adrenergic receptor-dependent manner. Repeated social defeat also significantly increased the number of CD11b(+)/CD45(high)/Ly6C(high) macrophages that trafficked to the brain. In addition, several inflammatory markers were increased on the surface of microglia (CD14, CD86, and TLR4) and macrophages (CD14 and CD86) after social defeat. Repeated social defeat also increased the presence of deramified microglia in the medial amygdala, prefrontal cortex, and hippocampus. Moreover, mRNA analysis of microglia indicated that repeated social defeat increased levels of interleukin (IL)-1β and reduced levels of glucocorticoid responsive genes [glucocorticoid-induced leucine zipper (GILZ) and FK506 binding protein-51 (FKBP51)]. The stress-dependent changes in microglia and macrophages were prevented by propranolol, a β-adrenergic receptor antagonist. Microglia isolated from socially defeated mice and cultured ex vivo produced markedly higher levels of IL-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 after stimulation with lipopolysaccharide compared with microglia from control mice. Last, repeated social defeat increased c-Fos activation in IL-1 receptor type-1-deficient mice, but did not promote anxiety-like behavior or microglia activation in the absence of functional IL-1 receptor type-1. These findings indicate that repeated social defeat-induced anxiety-like behavior and enhanced reactivity of microglia was dependent on activation of β-adrenergic and IL-1 receptors.",
"title": "β-Adrenergic receptor antagonism prevents anxiety-like behavior and microglial reactivity induced by repeated social defeat."
},
{
"docid": "23816832",
"text": "Diagnosis of multiple sclerosis (MS) requires the exclusion of other possible diagnoses. For this reason, the cerebrospinal fluid (CSF) should be routinely analysed in patients with a first clinical event suggestive of MS. CSF analysis is no longer mandatory for diagnosis of relapsing–remitting MS, as long as MRI diagnostic criteria are fulfilled. However, caution is required in diagnosing MS in patients with negative MRI findings or in the absence of CSF analysis, as CSF investigation is useful to eliminate other causes of disease. The detection of oligoclonal IgG bands in CSF has potential prognostic value and is helpful for clinical decision-making. In addition, CSF analysis is important for research into the pathogenesis of MS. Pathophysiological and neurodegenerative findings of inflammation in MS have been derived from CSF investigations. Novel CSF biomarkers, though not yet validated, have been identified for diagnosis of MS and for ascertaining disease activity, prognosis and response to treatment, and are likely to increase in number with modern detection techniques. In this Review, we summarize CSF findings that shed light on the differential diagnosis of MS, and highlight the potential of novel biomarkers for this disease that could advance understanding of its pathophysiology.",
"title": "The utility of cerebrospinal fluid analysis in patients with multiple sclerosis"
},
{
"docid": "15248287",
"text": "Neutrophil apoptosis is a highly regulated process essential for inflammation resolution, the molecular mechanisms of which are only partially elucidated. In this study, we describe a survival pathway controlled by proliferating cell nuclear antigen (PCNA), a nuclear factor involved in DNA replication and repairing of proliferating cells. We show that mature neutrophils, despite their inability to proliferate, express high levels of PCNA exclusively in their cytosol and constitutively associated with procaspases, presumably to prevent their activation. Notably, cytosolic PCNA abundance decreased during apoptosis, and increased during in vitro and in vivo exposure to the survival factor granulocyte colony-stimulating factor (G-CSF). Peptides derived from the cyclin-dependent kinase inhibitor p21, which compete with procaspases to bind PCNA, triggered neutrophil apoptosis thus demonstrating that specific modification of PCNA protein interactions affects neutrophil survival. Furthermore, PCNA overexpression rendered neutrophil-differentiated PLB985 myeloid cells significantly more resistant to TNF-related apoptosis-inducing ligand- or gliotoxin-induced apoptosis. Conversely, a decrease in PCNA expression after PCNA small interfering RNA transfection sensitized these cells to apoptosis. Finally, a mutation in the PCNA interdomain-connecting loop, the binding site for many partners, significantly decreased the PCNA-mediated antiapoptotic effect. These results identify PCNA as a regulator of neutrophil lifespan, thereby highlighting a novel target to potentially modulate pathological inflammation.",
"title": "Proliferating cell nuclear antigen acts as a cytoplasmic platform controlling human neutrophil survival"
},
{
"docid": "12122482",
"text": "We compared the diagnostic capabilities of MRI to CT, evoked potentials (EP), and CSF oligoclonal banding analysis in a prospective evaluation of 200 patients with suspected multiple sclerosis (MS). MRI was the best method for demonstrating dissemination in space. An abnormal appropriate EP in monosymptomatic disease was usually supported by MRI and CSF analysis as being predictive of MS as a clinical diagnosis. A normal appropriate EP study was not satisfactory because MRI and CSF analysis often did not support a diagnosis of non-MS. When there is agreement between three of these paraclinical studies, the diagnosis of MS is probably unequivocal. For use in research studies, laboratory-supported definite MS (LSDMS) could be diagnosed in 85 patients of the total 200 (42.5%), in 19/38 (50%) of optic neuritis (ON) patients, and in 24/52 (46%) of chronic progressive myelopathy (CPM) patients. MRI was 100% successful in identifying patients who qualified for LSDMS in the ON and CPM groups. In a short follow-up (less than 1 year), 19/200 (10%) went on to develop clinically definite MS (CDMS), and MRI predicted that diagnosis in 18/19 (95%). Only long-term follow-up will show how well these studies and the category of LSDMS predict the development of CDMS. The clinical diagnosis of MS (CDMS), even though only 95% accurate, must remain the gold standard.",
"title": "MRI in the diagnosis of MS: a prospective study with comparison of clinical evaluation, evoked potentials, oligoclonal banding, and CT."
},
{
"docid": "2014909",
"text": "Myeloid-derived suppressor cells (MDSCs) play critical roles in primary and metastatic cancer progression. MDSC regulation is widely variable even among patients harbouring the same type of malignancy, and the mechanisms governing such heterogeneity are largely unknown. Here, integrating human tumour genomics and syngeneic mammary tumour models, we demonstrate that mTOR signalling in cancer cells dictates a mammary tumour's ability to stimulate MDSC accumulation through regulating G-CSF. Inhibiting this pathway or its activators (for example, FGFR) impairs tumour progression, which is partially rescued by restoring MDSCs or G-CSF. Tumour-initiating cells (TICs) exhibit elevated G-CSF. MDSCs reciprocally increase TIC frequency through activating Notch in tumour cells, forming a feedforward loop. Analyses of primary breast cancers and patient-derived xenografts corroborate these mechanisms in patients. These findings establish a non-canonical oncogenic role of mTOR signalling in recruiting pro-tumorigenic MDSCs and show how defined cancer subsets may evolve to promote and depend on a distinct immune microenvironment.",
"title": "Oncogenic mTOR signaling recruits myeloid-derived suppressor cells to promote tumor initiation"
},
{
"docid": "4505748",
"text": "BACKGROUND The apolipoprotein E (APOE) genotype provides information on the risk of Alzheimer's disease, but the genotyping of patients and their family members has been discouraged. We examined the effect of genotype disclosure in a prospective, randomized, controlled trial. METHODS We randomly assigned 162 asymptomatic adults who had a parent with Alzheimer's disease to receive the results of their own APOE genotyping (disclosure group) or not to receive such results (nondisclosure group). We measured symptoms of anxiety, depression, and test-related distress 6 weeks, 6 months, and 1 year after disclosure or nondisclosure. RESULTS There were no significant differences between the two groups in changes in time-averaged measures of anxiety (4.5 in the disclosure group and 4.4 in the nondisclosure group, P=0.84), depression (8.8 and 8.7, respectively; P=0.98), or test-related distress (6.9 and 7.5, respectively; P=0.61). Secondary comparisons between the nondisclosure group and a disclosure subgroup of subjects carrying the APOE epsilon4 allele (which is associated with increased risk) also revealed no significant differences. However, the epsilon4-negative subgroup had a significantly lower level of test-related distress than did the epsilon4-positive subgroup (P=0.01). Subjects with clinically meaningful changes in psychological outcomes were distributed evenly among the nondisclosure group and the epsilon4-positive and epsilon4-negative subgroups. Baseline scores for anxiety and depression were strongly associated with post-disclosure scores of these measures (P<0.001 for both comparisons). CONCLUSIONS The disclosure of APOE genotyping results to adult children of patients with Alzheimer's disease did not result in significant short-term psychological risks. Test-related distress was reduced among those who learned that they were APOE epsilon4-negative. Persons with high levels of emotional distress before undergoing genetic testing were more likely to have emotional difficulties after disclosure. (ClinicalTrials.gov number, NCT00571025.)",
"title": "Disclosure of APOE genotype for risk of Alzheimer's disease."
},
{
"docid": "45449835",
"text": "Myelin-directed autoimmunity is considered to play a key role in the pathogenesis of multiple sclerosis (MS). Increased production of both pro- and anti-inflammatory cytokines is a common finding in MS. Interleukin-17 (IL-17) is a recently described cytokine produced in humans almost exclusively by activated memory T cells, which can induce the production of proinflammatory cytokines and chemokines from parenchymal cells and macrophages. In situ hybridisation with synthetic oligonucleotide probes was adopted to detect and enumerate IL-17 mRNA expressing mononuclear cells (MNC) in blood and cerebrospinal fluid (CSF) from patients with MS and control individuals. Numbers of IL-17 mRNA expressing blood MNC were higher in patients with MS and acute aseptic meningoencephalitis (AM) compared to healthy individuals. Higher numbers of IL-17 mRNA expressing blood MNC were detected in MS patients examined during clinical exacerbation compared to remission. Patients with MS had higher numbers of IL-17 mRNA expressing MNC in CSF compared to blood. This increase in numbers of IL-17 mRNA expressing MNC in CSF was not observed in patients with AM. Our results thus demonstrate increased numbers of IL-17 mRNA expressing MNC in MS with higher numbers in CSF than blood, and with the highest numbers in blood during clinical exacerbations.",
"title": "Interleukin-17 mRNA expression in blood and CSF mononuclear cells is augmented in multiple sclerosis."
},
{
"docid": "3078080",
"text": "UNLABELLED Fast, definitive diagnosis of Creutzfeldt-Jakob disease (CJD) is important in assessing patient care options and transmission risks. Real-time quaking-induced conversion (RT-QuIC) assays of cerebrospinal fluid (CSF) and nasal-brushing specimens are valuable in distinguishing CJD from non-CJD conditions but have required 2.5 to 5 days. Here, an improved RT-QuIC assay is described which identified positive CSF samples within 4 to 14 h with better analytical sensitivity. Moreover, analysis of 11 CJD patients demonstrated that while 7 were RT-QuIC positive using the previous conditions, 10 were positive using the new assay. In these and further analyses, a total of 46 of 48 CSF samples from sporadic CJD patients were positive, while all 39 non-CJD patients were negative, giving 95.8% diagnostic sensitivity and 100% specificity. This second-generation RT-QuIC assay markedly improved the speed and sensitivity of detecting prion seeds in CSF specimens from CJD patients. This should enhance prospects for rapid and accurate ante mortem CJD diagnosis. IMPORTANCE A long-standing problem in dealing with various neurodegenerative protein misfolding diseases is early and accurate diagnosis. This issue is particularly important with human prion diseases, such as CJD, because prions are deadly, transmissible, and unusually resistant to decontamination. The recently developed RT-QuIC test allows for highly sensitive and specific detection of CJD in human cerebrospinal fluid and is being broadly implemented as a key diagnostic tool. However, as currently applied, RT-QuIC takes 2.5 to 5 days and misses 11 to 23% of CJD cases. Now, we have markedly improved RT-QuIC analysis of human CSF such that CJD and non-CJD patients can be discriminated in a matter of hours rather than days with enhanced sensitivity. These improvements should allow for much faster, more accurate, and practical testing for CJD. In broader terms, our study provides a prototype for tests for misfolded protein aggregates that cause many important amyloid diseases, such as Alzheimer's, Parkinson's, and tauopathies.",
"title": "Rapid and Sensitive RT-QuIC Detection of Human Creutzfeldt-Jakob Disease Using Cerebrospinal Fluid"
},
{
"docid": "791050",
"text": "OBJECTIVE To determine whether higher past exposure to particulate air pollution is associated with prevalent high symptoms of anxiety. DESIGN Observational cohort study. SETTING Nurses' Health Study. PARTICIPANTS 71,271 women enrolled in the Nurses' Health Study residing throughout the contiguous United States who had valid estimates on exposure to particulate matter for at least one exposure period of interest and data on anxiety symptoms. MAIN OUTCOME MEASURES Meaningfully high symptoms of anxiety, defined as a score of 6 points or greater on the phobic anxiety subscale of the Crown-Crisp index, administered in 2004. RESULTS The 71,271 eligible women were aged between 57 and 85 years (mean 70 years) at the time of assessment of anxiety symptoms, with a prevalence of high anxiety symptoms of 15%. Exposure to particulate matter was characterized using estimated average exposure to particulate matter <2.5 μm in diameter (PM2.5) and 2.5 to 10 μm in diameter (PM2.5-10) in the one month, three months, six months, one year, and 15 years prior to assessment of anxiety symptoms, and residential distance to the nearest major road two years prior to assessment. Significantly increased odds of high anxiety symptoms were observed with higher exposure to PM2.5 for multiple averaging periods (for example, odds ratio per 10 µg/m(3) increase in prior one month average PM2.5: 1.12, 95% confidence interval 1.06 to 1.19; in prior 12 month average PM2.5: 1.15, 1.06 to 1.26). Models including multiple exposure windows suggested short term averaging periods were more relevant than long term averaging periods. There was no association between anxiety and exposure to PM2.5-10. Residential proximity to major roads was not related to anxiety symptoms in a dose dependent manner. CONCLUSIONS Exposure to fine particulate matter (PM2.5) was associated with high symptoms of anxiety, with more recent exposures potentially more relevant than more distant exposures. Research evaluating whether reductions in exposure to ambient PM2.5 would reduce the population level burden of clinically relevant symptoms of anxiety is warranted.",
"title": "The relation between past exposure to fine particulate air pollution and prevalent anxiety: observational cohort study"
},
{
"docid": "4695046",
"text": "OBJECTIVES To examine the effect of routinely administered psychiatric questionnaires on the recognition, management, and outcome of psychiatric disorders in non-psychiatric settings. DATA SOURCES Embase, Medline, PsycLIT, Cinahl, Cochrane Controlled Trials Register, and hand searches of key journals. METHODS A systematic review of randomised controlled trials of the administration and routine feedback of psychiatric screening and outcome questionnaires to clinicians in non-psychiatric settings. Narrative overview of key design features and end points, together with a random effects quantitative synthesis of comparable studies. MAIN OUTCOME MEASURES Recognition of psychiatric disorders after feedback of questionnaire results; interventions for psychiatric disorders; and outcome of psychiatric disorders. RESULTS Nine randomised studies were identified that examined the use of common psychiatric instruments in primary care and general hospital settings. Studies compared the effect of the administration of these instruments followed by the feedback of the results to clinicians, with administration with no feedback. Meta-analytic pooling was possible for four of these studies (2457 participants), which measured the effect of feedback on the recognition of depressive disorders. Routine administration and feedback of scores for all patients (irrespective of score) did not increase the overall rate of recognition of mental disorders such as anxiety and depression (relative risk of detection of depression by clinician after feedback 0.95, 95% confidence interval 0.83 to 1.09). Two studies showed that routine administration followed by selective feedback for only high scorers increased the rate of recognition of depression (relative risk of detection of depression after feedback 2.64, 1.62 to 4.31). This increased recognition, however, did not translate into an increased rate of intervention. Overall, studies of routine administration of psychiatric measures did not show an effect on patient outcome. CONCLUSIONS The routine measurement of outcome is a costly exercise. Little evidence shows that it is of benefit in improving psychosocial outcomes of those with psychiatric disorder managed in non-psychiatric settings.",
"title": "Anxiety"
},
{
"docid": "10190462",
"text": "Background: Reduced brain insulin signaling and low CSF-to-plasma insulin ratios have been observed in patients with Alzheimer disease (AD). Furthermore, intracerebroventricular or IV insulin administration improve memory, alter evoked potentials, and modulate neurotransmitters, possibly by augmenting low brain levels. After intranasal administration, insulin-like peptides follow extracellular pathways to the brain within 15 minutes. Objective: We tested the hypothesis that daily intranasal insulin treatment would facilitate cognition in patients with early AD or its prodrome, amnestic mild cognitive impairment (MCI). The proportion of verbal information retained after a delay period was the planned primary outcome measure. Secondary outcome measures included attention, caregiver rating of functional status, and plasma levels of insulin, glucose, β-amyloid, and cortisol. Methods: Twenty-five participants were randomly assigned to receive either placebo (n = 12) or 20 IU BID intranasal insulin treatment (n = 13) using an electronic atomizer, and 24 participants completed the study. Participants, caregivers, and all clinical evaluators were blinded to treatment assignment. Cognitive measures and blood were obtained at baseline and after 21 days of treatment. Results: Fasting plasma glucose and insulin were unchanged with treatment. The insulin-treated group retained more verbal information after a delay compared with the placebo-assigned group ( p = 0.0374). Insulin-treated subjects also showed improved attention ( p = 0.0108) and functional status ( p = 0.0410). Insulin treatment raised fasting plasma concentrations of the short form of the β-amyloid peptide (Aβ40; p = 0.0471) without affecting the longer isoform (Aβ42), resulting in an increased Aβ40/42 ratio ( p = 0.0207). Conclusions: The results of this pilot study support further investigation of the benefits of intranasal insulin for patients with Alzheimer disease, and suggest that intranasal peptide administration may be a novel approach to the treatment of neurodegenerative disorders.",
"title": "INTRANASAL INSULIN IMPROVES COGNITION AND MODULATES β-AMYLOID IN EARLY AD"
},
{
"docid": "44500794",
"text": "The aim of this study was to compare the effects of the genetic and pharmacological disruption of CB1 cannabinoid receptors on the elevated plus-maze test of anxiety. In the first experiment, the behaviour of CB1-knockout mice and wild-type mice was compared. In the second experiment, the cannabinoid antagonist SR141716A (0, 1, and 3 mg/kg) was administered to both CB1-knockout and wild type mice. Untreated CB1-knockout mice showed a reduced exploration of the open arms of the plus-maze apparatus, thus appearing more anxious than the wild-type animals, however no changes in locomotion were noticed. The vehicle-injected CB1-knockout mice from the second experiment also showed increased anxiety as compared with wild types. Surprisingly, the cannabinoid antagonist SR141716A reduced anxiety in both wild type and CB1 knockout mice. Locomotor behaviour was only marginally affected. Recent evidence suggests the existence of a novel cannabinoid receptor in the brain. It has also been shown that SR141716A binds to both the CB1 and the putative novel receptor. The data presented here supports these findings, as the cannabinoid receptor antagonist affected anxiety in both wild type and CB1-knockout mice. Tentatively, it may be suggested that the discrepancy between the effects of the genetic and pharmacological blockade of the CB1 receptor suggests that the novel receptor plays a role in anxiety.",
"title": "The effects of genetic and pharmacological blockade of the CB1 cannabinoid receptor on anxiety."
},
{
"docid": "21246752",
"text": "OBJECTIVE Mitochondrial disorders are caused by gene mutations in mitochondrial or nuclear DNA and affect energy-dependent organs such as the brain. Patients with psychiatric illness, particularly those with medical comorbidities, may have primary mitochondrial disorders. To date, this issue has received little attention in the literature, and mitochondrial disorders are likely underdiagnosed in psychiatric patients. DATA SOURCES This article describes a patient who presented with borderline personality disorder and treatment-resistant depression and was ultimately diagnosed with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) 3271. We also searched the literature for all case reports of patients with mitochondrial disorders who initially present with prominent psychiatric symptoms by using MEDLINE (from 1948-February 2011), Embase (from 1980-February 2011), PsycINFO (from 1806-February 2011), and the search terms mitochondrial disorder, mitochondria, psychiatry, mental disorders, major depression, anxiety, schizophrenia, and psychosis. STUDY SELECTION Fifty cases of mitochondrial disorders with prominent psychiatric symptomatology were identified. DATA EXTRACTION Information about the psychiatric presentation of the cases was extracted. This information was combined with our case, the most common psychiatric manifestations of mitochondrial disorders were identified, and the important diagnostic and treatment implications for patients with psychiatric illness were reviewed. RESULTS The most common psychiatric presentations in the cases of mitochondrial disorders included mood disorder, cognitive deterioration, psychosis, and anxiety. The most common diagnosis (52% of cases) was a MELAS mutation. Other genetic mitochondrial diagnoses included polymerase gamma mutations, Kearns-Sayre syndrome, mitochondrial DNA deletions, point mutations, twinkle mutations, and novel mutations. CONCLUSIONS Patients with mitochondrial disorders can present with primary psychiatric symptomatology, including mood disorder, cognitive impairment, psychosis, and anxiety. Psychiatrists need to be aware of the clinical features that are indicative of a mitochondrial disorder, investigate patients with suggestive presentations, and be knowledgeable about the treatment implications of the diagnosis.",
"title": "The psychiatric manifestations of mitochondrial disorders: a case and review of the literature."
},
{
"docid": "9604301",
"text": "UNLABELLED Cryptococcosis is a multifaceted fungal infection with variable clinical presentation and outcome. As in many infectious diseases, this variability is commonly assigned to host factors. To investigate whether the diversity of Cryptococcus neoformans clinical (ClinCn) isolates influences the interaction with host cells and the clinical outcome, we developed and validated new quantitative assays using flow cytometry and J774 macrophages. The phenotype of ClinCn-macrophage interactions was determined for 54 ClinCn isolates recovered from cerebrospinal fluids (CSF) from 54 unrelated patients, based on phagocytic index (PI) and 2-h and 48-h intracellular proliferation indexes (IPH2 and IPH48, respectively). Their phenotypes were highly variable. Isolates harboring low PI/low IPH2 and high PI/high IPH2 values were associated with nonsterilization of CSF at week 2 and death at month 3, respectively. A subset of 9 ClinCn isolates with different phenotypes exhibited variable virulence in mice and displayed intramacrophagic expression levels of the LAC1, APP1, VAD1, IPC1, PLB1, and COX1 genes that were highly variable among the isolates and correlated with IPH48. Variation in the expression of virulence factors is thus shown here to depend on not only experimental conditions but also fungal background. These results suggest that, in addition to host factors, the patient's outcome can be related to fungal determinants. Deciphering the molecular events involved in C. neoformans fate inside host cells is crucial for our understanding of cryptococcosis pathogenesis. IMPORTANCE Cryptococcus neoformans is a life-threatening human fungal pathogen that is responsible for an estimated 1 million cases of meningitis/year, predominantly in HIV-infected patients. The diversity of infecting isolates is well established, as is the importance of the host factors. Interaction with macrophages is a major step in cryptococcosis pathogenesis. How the diversity of clinical isolates influences macrophages' interactions and impacts cryptococcosis outcome in humans remains to be elucidated. Using new assays, we uncovered how yeast-macrophage interactions were highly variable among clinical isolates and found an association between specific behaviors and cryptococcosis outcome. In addition, gene expression of some virulence factors and intracellular proliferation were correlated. While many studies have established that virulence factors can be differentially expressed as a function of experimental conditions, our study demonstrates that, under the same experimental conditions, clinical isolates behaved differently, a diversity that could participate in the variable outcome of infection in humans.",
"title": "Dynamics of Cryptococcus neoformans-Macrophage Interactions Reveal that Fungal Background Influences Outcome during Cryptococcal Meningoencephalitis in Humans"
},
{
"docid": "5132358",
"text": "Chimeric antigen receptor-modified T cells with specificity for CD19 have shown promise in the treatment of chronic lymphocytic leukemia (CLL). It remains to be established whether chimeric antigen receptor T cells have clinical activity in acute lymphoblastic leukemia (ALL). Two children with relapsed and refractory pre-B-cell ALL received infusions of T cells transduced with anti-CD19 antibody and a T-cell signaling molecule (CTL019 chimeric antigen receptor T cells), at a dose of 1.4×10(6) to 1.2×10(7) CTL019 cells per kilogram of body weight. In both patients, CTL019 T cells expanded to a level that was more than 1000 times as high as the initial engraftment level, and the cells were identified in bone marrow. In addition, the chimeric antigen receptor T cells were observed in the cerebrospinal fluid (CSF), where they persisted at high levels for at least 6 months. Eight grade 3 or 4 adverse events were noted. The cytokine-release syndrome and B-cell aplasia developed in both patients. In one child, the cytokine-release syndrome was severe; cytokine blockade with etanercept and tocilizumab was effective in reversing the syndrome and did not prevent expansion of chimeric antigen receptor T cells or reduce antileukemic efficacy. Complete remission was observed in both patients and is ongoing in one patient at 11 months after treatment. The other patient had a relapse, with blast cells that no longer expressed CD19, approximately 2 months after treatment. Chimeric antigen receptor-modified T cells are capable of killing even aggressive, treatment-refractory acute leukemia cells in vivo. The emergence of tumor cells that no longer express the target indicates a need to target other molecules in addition to CD19 in some patients with ALL.",
"title": "Chimeric antigen receptor-modified T cells for acute lymphoid leukemia."
},
{
"docid": "10430148",
"text": "CONTEXT No antidiabetic regimen has demonstrated the ability to reduce progression of coronary atherosclerosis. Commonly used oral glucose-lowering agents include sulfonylureas, which are insulin secretagogues, and thiazolidinediones, which are insulin sensitizers. OBJECTIVE To compare the effects of an insulin sensitizer, pioglitazone, with an insulin secretagogue, glimepiride, on the progression of coronary atherosclerosis in patients with type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS Double-blind, randomized, multicenter trial at 97 academic and community hospitals in North and South America (enrollment August 2003-March 2006) in 543 patients with coronary disease and type 2 diabetes. INTERVENTIONS A total of 543 patients underwent coronary intravascular ultrasonography and were randomized to receive glimepiride, 1 to 4 mg, or pioglitazone, 15 to 45 mg, for 18 months with titration to maximum dosage, if tolerated. Atherosclerosis progression was measured by repeat intravascular ultrasonography examination in 360 patients at study completion. MAIN OUTCOME MEASURE Change in percent atheroma volume (PAV) from baseline to study completion. RESULTS Least squares mean PAV increased 0.73% (95% CI, 0.33% to 1.12%) with glimepiride and decreased 0.16% (95% CI, -0.57% to 0.25%) with pioglitazone(P = .002). An alternative analysis imputing values for noncompleters based on baseline characteristics showed an increase in PAV of 0.64% (95% CI, 0.23% to 1.05%) for glimepiride and a decrease of 0.06% (-0.47% to 0.35%) for pioglitazone (between-group P = .02). Mean (SD) baseline HbA(1c) levels were 7.4% (1.0%) in both groups and declined during treatment an average 0.55% (95% CI, -0.68% to -0.42%) with pioglitazone and 0.36% (95% CI, -0.48% to -0.24%) with glimepiride (between-group P = .03). In the pioglitazone group, compared with glimepiride, high-density lipoprotein levels increased 5.7 mg/dL (95% CI, 4.4 to 7.0 mg/dL; 16.0%) vs 0.9 mg/dL (95% CI, -0.3 to 2.1 mg/dL; 4.1%), and median triglyceride levels decreased 16.3 mg/dL (95% CI, -27.7 to -11.0 mg/dL; 15.3%) vs an increase of 3.3 mg/dL (95% CI, -10.7 to 11.7 mg/dL; 0.6%) (P < .001 for both comparisons). Median fasting insulin levels decreased with pioglitazone and increased with glimepiride (P < .001). Hypoglycemia was more common in the glimepiride group and edema, fractures, and decreased hemoglobin levels occurred more frequently in the pioglitazone group. CONCLUSION In patients with type 2 diabetes and coronary artery disease, treatment with pioglitazone resulted in a significantly lower rate of progression of coronary atherosclerosis compared with glimepiride. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00225277.",
"title": "Comparison of pioglitazone vs glimepiride on progression of coronary atherosclerosis in patients with type 2 diabetes: the PERISCOPE randomized controlled trial."
},
{
"docid": "24612804",
"text": "IL-17 is a novel, CD4+ T cell-restricted cytokine. In vivo, it stimulates hematopoiesis and causes neutrophilia consisting of mature granulocytes. In this study, we show that IL-17-mediated granulopoiesis requires G-CSF release and the presence or induction of the transmembrane form of stem cell factor (SCF) for optimal granulopoiesis. However, IL-17 also protects mice from G-CSF neutralization-induced neutropenia. G-CSF neutralization completely reversed IL-17-induced BM progenitor expansion, whereas splenic CFU-GM/CFU-granulocyte-erythrocyte-megakaryocyte-monocyte was only reduced by 50% in both Sl/Sld and littermate control mice. Thus, there remained a significant SCF/G-CSF-independent effect of IL-17 on splenic granulopoiesis, resulting in a preservation of mature circulating granulocytes. IL-17 is a cytokine that potentially interconnects lymphocytic and myeloid host defense and may have potential for therapeutic development.",
"title": "Requirement of endogenous stem cell factor and granulocyte-colony-stimulating factor for IL-17-mediated granulopoiesis."
},
{
"docid": "38886345",
"text": "BACKGROUND JX-594 is a targeted oncolytic poxvirus designed to selectively replicate in and destroy cancer cells with cell-cycle abnormalities and epidermal growth factor receptor (EGFR)-ras pathway activation. Direct oncolysis plus granulocyte-macrophage colony-stimulating factor (GM-CSF) expression also stimulates shutdown of tumour vasculature and antitumoral immunity. We aimed to assess intratumoral injection of JX-594 in patients with refractory primary or metastatic liver cancer. METHODS Between Jan 4, 2006, and July 4, 2007, 14 patients with histologically confirmed refractory primary or metastatic liver tumours (up to 10.9 cm total diameter) that were amenable to image-guided intratumoral injections were enrolled into this non-comparative, open-label, phase I dose-escalation trial (standard 3x3 design; two to six patients for each dose with 12-18 estimated total patients). Patients received one of four doses of intratumoral JX-594 (10(8) plaque-forming units [pfu], 3x10(8) pfu, 10(9) pfu, or 3x10(9) pfu) every 3 weeks at Dong-A University Hospital (Busan, South Korea). Patients were monitored after treatment for at least 48 h in hospital and for at least 4 weeks as out-patients. Adverse event-monitoring according to the National Cancer Institute Common Toxicity Criteria (version 3) and standard laboratory toxicity grading for haematology, liver and renal function, coagulation studies, serum chemistry, and urinalysis were done. The primary aims were to ascertain the maximum-tolerated dose (MTD) and safety of JX-594 treatment. Data were also collected on pharmacokinetics, pharmacodynamics, and efficacy. Analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00629759. FINDINGS Of 22 patients with liver tumours who were assessed for eligibility, eight patients did not meet inclusion criteria. Therefore, 14 patients, including those with hepatocellular, colorectal, melanoma, and lung cancer, were enrolled. Patients were heavily pretreated (5.6 previous treatments, SD 2.8, range 2.0-12.0) and had large tumours (7.0 cm diameter, SD 2.7, range 1.8-10.9). Patients received a mean of 3.4 (SD 2.2, range 1.0-8.0) cycles of JX-594. All patients were evaluable for toxicity. All patients experienced grade I-III flu-like symptoms, and four had transient grade I-III dose-related thrombocytopenia. Grade III hyperbilirubinaemia was dose-limiting in both patients at the highest dose; the MTD was therefore 1x10(9) pfu. JX-594 replication-dependent dissemination in blood was shown, with resultant infection of non-injected tumour sites. GM-CSF expression resulted in grade I-III increases in neutrophil counts in four of six patients at the MTD. Tumour responses were shown in injected and non-injected tumours. Ten patients were radiographically evaluable for objective responses; non-evaluable patients had contraindications to contrast medium (n=2) or no post-treatment scans (n=2). According to Response Evaluation Criteria in Solid Tumors (RECIST), three patients had partial response, six had stable disease, and one had progressive disease. INTERPRETATION Intratumoral injection of JX-594 into primary or metastatic liver tumours was generally well-tolerated. Direct hyperbilirubinaemia was the dose-limiting toxicity. Safety was acceptable in the context of JX-594 replication, GM-CSF expression, systemic dissemination, and JX-594 had anti-tumoral effects against several refractory carcinomas. Phase II trials are now underway.",
"title": "Use of a targeted oncolytic poxvirus, JX-594, in patients with refractory primary or metastatic liver cancer: a phase I trial."
},
{
"docid": "20764484",
"text": "The psychoactive constituent of cannabis, Δ9-tetrahydrocannabinol, produces in humans subjective responses mediated by CB1 cannabinoid receptors, indicating that endogenous cannabinoids may contribute to the control of emotion. But the variable effects of Δ9-tetrahydrocannabinol obscure the interpretation of these results and limit the therapeutic potential of direct cannabinoid agonists. An alternative approach may be to develop drugs that amplify the effects of endogenous cannabinoids by preventing their inactivation. Here we describe a class of potent, selective and systemically active inhibitors of fatty acid amide hydrolase, the enzyme responsible for the degradation of the endogenous cannabinoid anandamide. Like clinically used anti-anxiety drugs, in rats the inhibitors exhibit benzodiazepine-like properties in the elevated zero-maze test and suppress isolation-induced vocalizations. These effects are accompanied by augmented brain levels of anandamide and are prevented by CB1 receptor blockade. Our results indicate that anandamide participates in the modulation of emotional states and point to fatty acid amide hydrolase inhibition as an innovative approach to anti-anxiety therapy.",
"title": "Modulation of anxiety through blockade of anandamide hydrolysis"
}
] |
804
|
Monoclonal antibody targeting of N-cadherin inhibits growth.
|
[
{
"docid": "22180793",
"text": "The transition from androgen-dependent to castration-resistant prostate cancer (CRPC) is a lethal event of uncertain molecular etiology. Comparing gene expression in isogenic androgen-dependent and CRPC xenografts, we found a reproducible increase in N-cadherin expression, which was also elevated in primary and metastatic tumors of individuals with CRPC. Ectopic expression of N-cadherin in nonmetastatic, androgen-dependent prostate cancer models caused castration resistance, invasion and metastasis. Monoclonal antibodies against the ectodomain of N-cadherin reduced proliferation, adhesion and invasion of prostate cancer cells in vitro. In vivo, these antibodies slowed the growth of multiple established CRPC xenografts, blocked local invasion and metastasis and, at higher doses, led to complete regression. N-cadherin–specific antibodies markedly delayed the time to emergence of castration resistance, markedly affected tumor histology and angiogenesis, and reduced both AKT serine-threonine kinase activity and serum interleukin-8 (IL-8) secretion. These data indicate that N-cadherin is a major cause of both prostate cancer metastasis and castration resistance. Therapeutic targeting of this factor with monoclonal antibodies may have considerable clinical benefit.",
"title": "Monoclonal antibody targeting of N-cadherin inhibits prostate cancer growth, metastasis and castration resistance"
}
] |
[
{
"docid": "6550579",
"text": "Epidermal growth factor receptor (EGFR) and HER3 each form heterodimers with HER2 and have independently been implicated as key coreceptors that drive HER2-amplified breast cancer. Some studies suggest a dominant role for EGFR, a notion of renewed interest given the development of dual HER2/EGFR small-molecule inhibitors. Other studies point to HER3 as the primary coreceptor. To clarify the relative contributions of EGFR and HER3 to HER2 signaling, we studied receptor knockdown via small interfering RNA technology across a panel of six HER2-overexpressing cell lines. Interestingly, HER3 was as critical as HER2 for maintaining cell proliferation in most cell lines, whereas EGFR was dispensable. Induction of HER3 knockdown in the HER2-overexpressing BT474M1 cell line was found to inhibit growth in three-dimensional culture and induce rapid tumor regression of in vivo xenografts. Furthermore, preferential phosphorylation of HER3, but not EGFR, was observed in HER2-amplified breast cancer tissues. Given these data suggesting HER3 as an important therapeutic target, we examined the activity of pertuzumab, a HER2 antibody that inhibits HER3 signaling by blocking ligand-induced HER2/HER3 heterodimerization. Pertuzumab inhibited ligand-dependent morphogenesis in three-dimensional culture and induced tumor regression in the heregulin-dependent MDA-MB-175 xenograft model. Importantly, these activities of pertuzumab were distinct from those of trastuzumab, a monoclonal antibody currently used for treatment of HER2-amplified breast cancer patients. Our data suggest that inhibition of HER3 may be more clinically relevant than inhibition of EGFR in HER2-amplified breast cancer and also suggest that adding pertuzumab to trastuzumab may augment therapeutic benefit by blocking HER2/HER3 signaling.",
"title": "A central role for HER3 in HER2-amplified breast cancer: implications for targeted therapy."
},
{
"docid": "23160444",
"text": "Neuronal growth cones move forward by dynamically connecting actin-based motility to substrate adhesion, but the mechanisms at the individual molecular level remain unclear. We cultured primary neurons on N-cadherin-coated micropatterned substrates, and imaged adhesion and cytoskeletal proteins at the ventral surface of growth cones using single particle tracking combined to photoactivated localization microscopy (sptPALM). We demonstrate transient interactions in the second time scale between flowing actin filaments and immobilized N-cadherin/catenin complexes, translating into a local reduction of the actin retrograde flow. Normal actin flow on micropatterns was rescued by expression of a dominant negative N-cadherin construct competing for the coupling between actin and endogenous N-cadherin. Fluorescence recovery after photobleaching (FRAP) experiments confirmed the differential kinetics of actin and N-cadherin, and further revealed a 20% actin population confined at N-cadherin micropatterns, contributing to local actin accumulation. Computer simulations with relevant kinetic parameters modeled N-cadherin and actin turnover well, validating this mechanism. Such a combination of short- and long-lived interactions between the motile actin network and spatially restricted adhesive complexes represents a two-tiered clutch mechanism likely to sustain dynamic environment sensing and provide the force necessary for growth cone migration.",
"title": "Two-tiered coupling between flowing actin and immobilized N-cadherin/catenin complexes in neuronal growth cones."
},
{
"docid": "27772649",
"text": "BACKGROUND & AIMS Celiac disease is characterized by disturbed jejunal crypt-villus axis biology with immunoglobulin (Ig) A deposits underlining the epithelium. The aim of this study was to test whether celiac disease serum IgA (reticulin/endomysial autoantibodies) interferes with the mesenchymal-epithelial cell cross-talk. METHODS Differentiation of T84 epithelial cells was induced with IMR-90 fibroblasts or transforming growth factor beta in three-dimensional collagen gel cultures. The effects of purified celiac IgA and monoclonal tissue transglutaminase antibodies (CUB7402) were studied by adding the antibodies to the cocultures. RESULTS Active celiac disease IgA, reactive for tissue transglutaminase, significantly inhibited T84 epithelial cell differentiation (P < 0.001) and increased epithelial cell proliferation (P = 0.024). Similar effects were obtained with antibodies against tissue transglutaminase. CONCLUSIONS Celiac disease-associated IgA class antibodies disturb transforming growth factor beta-mediated fibroblast-epithelial cell cross-talk in this in vitro crypt-villus axis model. This primary finding indicates that celiac disease-specific autoantibodies may also contribute to the formation of the gluten-triggered jejunal mucosal lesion in celiac disease.",
"title": "Serum immunoglobulin A from patients with celiac disease inhibits human T84 intestinal crypt epithelial cell differentiation."
},
{
"docid": "17188921",
"text": "Cell migration is a process which is essential during embryonic development, throughout adult life and in some pathological conditions. Cadherins, and more specifically the neural cell adhesion molecule N-cadherin, play an important role in migration. In embryogenesis, N-cadherin is the key molecule during gastrulation and neural crest development. N-cadherin mediated contacts activate several pathways like Rho GTPases and function in tyrosine kinase signalling (for example via the fibroblast growth factor receptor). In cancer, cadherins control the balance between suppression and promotion of invasion. E-cadherin functions as an invasion suppressor and is downregulated in most carcinomas, while N-cadherin, as an invasion promoter, is frequently upregulated. Expression of N-cadherin in epithelial cells induces changes in morphology to a fibroblastic phenotype, rendering the cells more motile and invasive. However in some cancers, like osteosarcoma, N-cadherin may behave as a tumour suppressor. N-cadherin can have multiple functions: promoting adhesion or induction of migration dependent on the cellular context.",
"title": "N-cadherin in the spotlight of cell-cell adhesion, differentiation, embryogenesis, invasion and signalling."
},
{
"docid": "4373433",
"text": "Broadly neutralizing antibodies against highly variable viral pathogens are much sought after to treat or protect against global circulating viruses. Here we probed the neutralizing antibody repertoires of four human immunodeficiency virus (HIV)-infected donors with remarkably broad and potent neutralizing responses and rescued 17 new monoclonal antibodies that neutralize broadly across clades. Many of the new monoclonal antibodies are almost tenfold more potent than the recently described PG9, PG16 and VRC01 broadly neutralizing monoclonal antibodies and 100-fold more potent than the original prototype HIV broadly neutralizing monoclonal antibodies. The monoclonal antibodies largely recapitulate the neutralization breadth found in the corresponding donor serum and many recognize novel epitopes on envelope (Env) glycoprotein gp120, illuminating new targets for vaccine design. Analysis of neutralization by the full complement of anti-HIV broadly neutralizing monoclonal antibodies now available reveals that certain combinations of antibodies should offer markedly more favourable coverage of the enormous diversity of global circulating viruses than others and these combinations might be sought in active or passive immunization regimes. Overall, the isolation of multiple HIV broadly neutralizing monoclonal antibodies from several donors that, in aggregate, provide broad coverage at low concentrations is a highly positive indicator for the eventual design of an effective antibody-based HIV vaccine.",
"title": "Broad neutralization coverage of HIV by multiple highly potent antibodies"
},
{
"docid": "7986878",
"text": "We previously reported that intetumumab (CNTO 95), a fully human anti-αv integrin monoclonal antibody, is a radiosensitizer in mice with xenograft tumors. Because intetumumab does not cross-react with mouse integrins, but has cross-reactivity with rat integrins, we next studied the potential combined use of radiation therapy and intetumumab in human cancer xenograft models in nude rats to assess effects on both tumor cells and the tumor microenvironment. Nude rats bearing human head and neck cancer and non-small cell lung cancer (NSCLC) xenografts were treated with intetumumab and fractionated local tumor radiotherapy. Effects on tumor growth and metastasis, blood perfusion, oxygenation, and gastrointestinal toxicity were studied. Intetumumab alone had a moderate effect on tumor growth. When combined with fractionated radiation therapy, intetumumab significantly inhibited tumor growth and produced a tumor response rate that was significantly better than with radiation therapy alone. Treatment with intetumumab also significantly reduced lung metastasis in the A549 NSCLC xenograft model. The oxygenation and blood perfusion in xenograft tumors measured by microbubble-enhanced ultrasound imaging were substantially increased after treatment with intetumumab. The combined use of intetumumab and radiation therapy reduced the microvessel density and increased apoptosis in tumor cells and the tumor microenvironment. Toxicity studies showed that treatment with intetumumab did not cause the histopathologic changes in the lungs and did not sensitize the sensitive gastrointestinal epithelium to the effect of radiation therapy. Intetumumab can potentiate the efficacy of fractionated radiation therapy in human cancer xenograft tumors in nude rats without increased toxicity.",
"title": "Anti-alphav integrin monoclonal antibody intetumumab enhances the efficacy of radiation therapy and reduces metastasis of human cancer xenografts in nude rats."
},
{
"docid": "13235609",
"text": "Inhibition of VEGF signaling leads to a proinvasive phenotype in mouse models of glioblastoma multiforme (GBM) and in a subset of GBM patients treated with bevacizumab. Here, we demonstrate that vascular endothelial growth factor (VEGF) directly and negatively regulates tumor cell invasion through enhanced recruitment of the protein tyrosine phosphatase 1B (PTP1B) to a MET/VEGFR2 heterocomplex, thereby suppressing HGF-dependent MET phosphorylation and tumor cell migration. Consequently, VEGF blockade restores and increases MET activity in GBM cells in a hypoxia-independent manner, while inducing a program reminiscent of epithelial-to-mesenchymal transition highlighted by a T-cadherin to N-cadherin switch and enhanced mesenchymal features. Inhibition of MET in GBM mouse models blocks mesenchymal transition and invasion provoked by VEGF ablation, resulting in substantial survival benefit.",
"title": "VEGF inhibits tumor cell invasion and mesenchymal transition through a MET/VEGFR2 complex."
},
{
"docid": "3825472",
"text": "Neural activity induces the remodeling of pre- and postsynaptic membranes, which maintain their apposition through cell adhesion molecules. Among them, N-cadherin is redistributed, undergoes activity-dependent conformational changes, and is required for synaptic plasticity. Here, we show that depolarization induces the enlargement of the width of spine head, and that cadherin activity is essential for this synaptic rearrangement. Dendritic spines visualized with green fluorescent protein in hippocampal neurons showed an expansion by the activation of AMPA receptor, so that the synaptic apposition zone may be expanded. N-cadherin-venus fusion protein laterally dispersed along the expanding spine head. Overexpression of dominant-negative forms of N-cadherin resulted in the abrogation of the spine expansion. Inhibition of actin polymerization with cytochalasin D abolished the spine expansion. Together, our data suggest that cadherin-based adhesion machinery coupled with the actin-cytoskeleton is critical for the remodeling of synaptic apposition zone.",
"title": "Cadherin activity is required for activity-induced spine remodeling"
},
{
"docid": "14149065",
"text": "E-cadherin has been linked to the suppression of tumor growth and the inhibition of cell proliferation in culture. We observed that progressively decreasing the seeding density of normal rat kidney-52E (NRK-52E) or MCF-10A epithelial cells from confluence, indeed, released cells from growth arrest. Unexpectedly, a further decrease in seeding density so that cells were isolated from neighboring cells decreased proliferation. Experiments using microengineered substrates showed that E-cadherin engagement stimulated the peak in proliferation at intermediate seeding densities, and that the proliferation arrest at high densities did not involve E-cadherin, but rather resulted from a crowding-dependent decrease in cell spreading against the underlying substrate. Rac1 activity, which was induced by E-cadherin engagement specifically at intermediate seeding densities, was required for the cadherin-stimulated proliferation, and the control of Rac1 activation by E-cadherin was mediated by p120-catenin. Together, these findings demonstrate a stimulatory role for E-cadherin in proliferative regulation, and identify a simple mechanism by which cell–cell contact may trigger or inhibit epithelial cell proliferation in different settings.",
"title": "E-cadherin engagement stimulates proliferation via Rac1"
},
{
"docid": "5123516",
"text": "Significant endeavor has been applied to identify functional therapeutic targets in glioblastoma (GBM) to halt the growth of this aggressive cancer. We show that the receptor tyrosine kinase EphA3 is frequently overexpressed in GBM and, in particular, in the most aggressive mesenchymal subtype. Importantly, EphA3 is highly expressed on the tumor-initiating cell population in glioma and appears critically involved in maintaining tumor cells in a less differentiated state by modulating mitogen-activated protein kinase signaling. EphA3 knockdown or depletion of EphA3-positive tumor cells reduced tumorigenic potential to a degree comparable to treatment with a therapeutic radiolabelled EphA3-specific monoclonal antibody. These results identify EphA3 as a functional, targetable receptor in GBM.",
"title": "EphA3 maintains tumorigenicity and is a therapeutic target in glioblastoma multiforme."
},
{
"docid": "31311495",
"text": "We have previously demonstrated that, following acquisition of endocrine resistance, breast cancer cells display an altered growth rate together with increased aggressive behaviour in vitro. Since dysfunctional cell-cell adhesive interactions can promote an aggressive phenotype, we investigated the integrity of this protein complex in our breast cancer model of tamoxifen resistance. In culture, tamoxifen-resistant MCF7 (TamR) cells grew as loosely packed colonies with loss of cell-cell junctions and demonstrated altered morphology characteristic of cells undergoing epithelial-to-mesenchymal transition (EMT). Neutralising E-cadherin function promoted the invasion and inhibited the aggregation of endocrine-sensitive MCF7 cells, whilst having little effect on the behaviour of TamR cells. Additionally, TamR cells had increased levels of tyrosine-phosphorylated beta-catenin, whilst serine/threonine-phosphorylated beta-catenin was decreased. These cells also displayed loss of association between beta-catenin and E-cadherin, increased cytoplasmic and nuclear beta-catenin and elevated transcription of beta-catenin target genes known to be involved in tumour progression and EMT. Inhibition of EGFR kinase activity in TamR cells reduced beta-catenin tyrosine phosphorylation, increased beta-catenin-E-cadherin association and promoted cell-cell adhesion. In such treated cells, the association of beta-catenin with Lef-1 and the transcription of c-myc, cyclin-D1, CD44 and COX-2 were also reduced. These results suggest that homotypic adhesion in tamoxifen-resistant breast cancer cells is dysfunctional due to EGFR-driven modulation of the phosphorylation status of beta-catenin and may contribute to an enhanced aggressive phenotype and transition towards a mesenchymal phenotype in vitro.",
"title": "Tamoxifen resistance in MCF7 cells promotes EMT-like behaviour and involves modulation of beta-catenin phosphorylation."
},
{
"docid": "1454773",
"text": "The programmed death-1 (PD-1) receptor serves as an immunologic checkpoint, limiting bystander tissue damage and preventing the development of autoimmunity during inflammatory responses. PD-1 is expressed by activated T cells and downmodulates T-cell effector functions upon binding to its ligands, PD-L1 and PD-L2, on antigen-presenting cells. In patients with cancer, the expression of PD-1 on tumor-infiltrating lymphocytes and its interaction with the ligands on tumor and immune cells in the tumor microenvironment undermine antitumor immunity and support its rationale for PD-1 blockade in cancer immunotherapy. This report details the development and characterization of nivolumab, a fully human IgG4 (S228P) anti-PD-1 receptor-blocking monoclonal antibody. Nivolumab binds to PD-1 with high affinity and specificity, and effectively inhibits the interaction between PD-1 and its ligands. In vitro assays demonstrated the ability of nivolumab to potently enhance T-cell responses and cytokine production in the mixed lymphocyte reaction and superantigen or cytomegalovirus stimulation assays. No in vitro antibody-dependent cell-mediated or complement-dependent cytotoxicity was observed with the use of nivolumab and activated T cells as targets. Nivolumab treatment did not induce adverse immune-related events when given to cynomolgus macaques at high concentrations, independent of circulating anti-nivolumab antibodies where observed. These data provide a comprehensive preclinical characterization of nivolumab, for which antitumor activity and safety have been demonstrated in human clinical trials in various solid tumors.",
"title": "In vitro characterization of the anti-PD-1 antibody nivolumab, BMS-936558, and in vivo toxicology in non-human primates."
},
{
"docid": "36642096",
"text": "BACKGROUND Type 1 diabetes mellitus is a chronic autoimmune disease caused by the pathogenic action of T lymphocytes on insulin-producing beta cells. Previous clinical studies have shown that continuous immune suppression temporarily slows the loss of insulin production. Preclinical studies suggested that a monoclonal antibody against CD3 could reverse hyperglycemia at presentation and induce tolerance to recurrent disease. METHODS We studied the effects of a nonactivating humanized monoclonal antibody against CD3--hOKT3gamma1(Ala-Ala)--on the loss of insulin production in patients with type 1 diabetes mellitus. Within 6 weeks after diagnosis, 24 patients were randomly assigned to receive either a single 14-day course of treatment with the monoclonal antibody or no antibody and were studied during the first year of disease. RESULTS Treatment with the monoclonal antibody maintained or improved insulin production after one year in 9 of the 12 patients in the treatment group, whereas only 2 of the 12 controls had a sustained response (P=0.01). The treatment effect on insulin responses lasted for at least 12 months after diagnosis. Glycosylated hemoglobin levels and insulin doses were also reduced in the monoclonal-antibody group. No severe side effects occurred, and the most common side effects were fever, rash, and anemia. Clinical responses were associated with a change in the ratio of CD4+ T cells to CD8+ T cells 30 and 90 days after treatment. CONCLUSIONS Treatment with hOKT3gamma1(Ala-Ala) mitigates the deterioration in insulin production and improves metabolic control during the first year of type 1 diabetes mellitus in the majority of patients. The mechanism of action of the anti-CD3 monoclonal antibody may involve direct effects on pathogenic T cells, the induction of populations of regulatory cells, or both.",
"title": "Anti-CD3 monoclonal antibody in new-onset type 1 diabetes mellitus."
},
{
"docid": "25543207",
"text": "Platelet inhibitors are the mainstay treatment for patients with vascular diseases. The current 'gold standard' antiplatelet agent clopidogrel has several pharmacological and clinical limitations that have prompted the search for more effective platelet antagonists. The candidates include various blockers of the purinergic P2Y12 receptor such as prasugrel, an oral irreversible thienopyridine; two adenosine triphosphate analogues that bind reversibly to the P2Y12 receptor: ticagrelor (oral) and cangrelor (intravenous); elinogrel, a direct-acting reversible P2Y12 receptor inhibitor (the only antiplatelet compound that can be administered both intravenously and orally); BX 667, an orally active and reversible small-molecule P2Y12 receptor antagonist; SCH 530348, SCH 205831, SCH 602539 and E5555, highly selective and orally active antagonists on the protease-activated receptor 1. A number of drugs also hit new targets: terutroban, an oral, selective and specific inhibitor of the thromboxane receptor; ARC1779, a second-generation, nuclease resistant aptamer which inhibits von Willebrand factor-dependent platelet aggregation; ALX-0081, a bivalent humanized nanobody targeting the GPIb binding site of von Willebrand factor and AJW200, an IgG4 monoclonal antibody of von Willebrand factor. The pharmacology and clinical profiles of new platelet antagonists indicate that they provide more consistent, more rapid and more potent platelet inhibition than agents currently used. Whether these potential advantages will translate into clinical advantages will require additional comparisons in properly powered, randomized, controlled trials.",
"title": "Pharmacokinetic, pharmacodynamic and clinical profile of novel antiplatelet drugs targeting vascular diseases."
},
{
"docid": "2593298",
"text": "Receptor endocytosis is a fundamental step in controlling the magnitude, duration, and nature of cell signaling events. Confluent endothelial cells are contact inhibited in their growth and respond poorly to the proliferative signals of vascular endothelial growth factor (VEGF). In a previous study, we found that the association of vascular endothelial cadherin (VEC) with VEGF receptor (VEGFR) type 2 contributes to density-dependent growth inhibition (Lampugnani, G.M., A. Zanetti, M. Corada, T. Takahashi, G. Balconi, F. Breviario, F. Orsenigo, A. Cattelino, R. Kemler, T.O. Daniel, and E. Dejana. 2003. J. Cell Biol. 161:793–804). In the present study, we describe the mechanism through which VEC reduces VEGFR-2 signaling. We found that VEGF induces the clathrin-dependent internalization of VEGFR-2. When VEC is absent or not engaged at junctions, VEGFR-2 is internalized more rapidly and remains in endosomal compartments for a longer time. Internalization does not terminate its signaling; instead, the internalized receptor is phosphorylated, codistributes with active phospholipase C–γ, and activates p44/42 mitogen-activated protein kinase phosphorylation and cell proliferation. Inhibition of VEGFR-2 internalization reestablishes the contact inhibition of cell growth, whereas silencing the junction-associated density-enhanced phosphatase-1/CD148 phosphatase restores VEGFR-2 internalization and signaling. Thus, VEC limits cell proliferation by retaining VEGFR-2 at the membrane and preventing its internalization into signaling compartments.",
"title": "Vascular endothelial cadherin controls VEGFR-2 internalization and signaling from intracellular compartments"
},
{
"docid": "19485649",
"text": "Transmembrane cadherins are calcium-dependent intercellular adhesion molecules. Recently, they have also been shown to be sites of actin assembly during adhesive contact formation. However, the roles of actin assembly on transmembrane cadherins during development are not fully understood. We show here, using the developing ectoderm of the Xenopus embryo as a model, that F-actin assembly is a primary function of both N-cadherin in the neural ectoderm and E-cadherin in the non-neural (epidermal) ectoderm, and that each cadherin is essential for the characteristic morphogenetic movements of these two tissues. However, depletion of N-cadherin and E-cadherin did not cause dissociation in these tissues at the neurula stage, probably owing to the expression of C-cadherin in each tissue. Depletion of each of these cadherins is not rescued by the other, nor by the expression of C-cadherin, which is expressed in both tissues. One possible reason for this is that each cadherin is expressed in a different domain of the cell membrane. These data indicate the combinatorial nature of cadherin function, the fact that N- and E-cadherin play primary roles in F-actin assembly in addition to roles in cell adhesion, and that this function is specific to individual cadherins. They also show how cell adhesion and motility can be combined in morphogenetic tissue movements that generate the form and shape of the embryonic organs.",
"title": "N- and E-cadherins in Xenopus are specifically required in the neural and non-neural ectoderm, respectively, for F-actin assembly and morphogenetic movements."
},
{
"docid": "9142761",
"text": "Plasmodium falciparum surface protein 25 (Pfs25) is a candidate for transmission-blocking vaccines (TBVs). Anti-Pfs25 antibodies block the development of oocysts in membrane-feeding assays and we have shown the activity correlates with antibody titer. In this study, we purified Pfs25-specific IgGs to convert antibody titer to microg/mL and determined the amount of antibody required to inhibit 50% of oocyst development (IC(50)). The IC(50) were, 15.9, 4.2, 41.2, and 85.6microg/mL for mouse, rabbit, monkey and human, respectively, and the differences among species were significant. Anti-Pfs25 sera from rabbit, monkey and human showed different patterns of competition against 6 mouse monoclonal antibodies, and the avidity of antibodies among four species were also different. These data suggests that information obtained from animal studies which assess efficacy of TBV candidates may be difficult to translate to human immunization.",
"title": "The IC(50) of anti-Pfs25 antibody in membrane-feeding assay varies among species."
},
{
"docid": "21185923",
"text": "CD25+CD4+ regulatory T cells in normal animals are engaged in the maintenance of immunological self-tolerance. We show here that glucocorticoid-induced tumor necrosis factor receptor family–related gene (GITR, also known as TNFRSF18)—a member of the tumor necrosis factor–nerve growth factor (TNF-NGF) receptor gene superfamily—is predominantly expressed on CD25+CD4+ T cells and on CD25+CD4+CD8− thymocytes in normal naïve mice. We found that stimulation of GITR abrogated CD25+CD4+ T cell–mediated suppression. In addition, removal of GITR-expressing T cells or administration of a monoclonal antibody to GITR produced organ-specific autoimmune disease in otherwise normal mice. Thus, GITR plays a key role in dominant immunological self-tolerance maintained by CD25+CD4+ regulatory T cells and could be a suitable molecular target for preventing or treating autoimmune disease.",
"title": "Stimulation of CD25+CD4+ regulatory T cells through GITR breaks immunological self-tolerance"
},
{
"docid": "2060137",
"text": "Cell-to-cell adhesions are crucial in maintaining the structural and functional integrity of cardiac cells. Little is known about the mechanosensitivity and mechanotransduction of cell-to-cell interactions. Most studies of cardiac mechanotransduction and myofibrillogenesis have focused on cell-extracellular matrix (ECM)-specific interactions. This study assesses the direct role of intercellular adhesion, specifically that of N-cadherin-mediated mechanotransduction, on the morphology and internal organization of neonatal ventricular cardiac myocytes. The results show that cadherin-mediated cell attachments are capable of eliciting a cytoskeletal network response similar to that of integrin-mediated force response and transmission, affecting myofibrillar organization, myocyte shape, and cortical stiffness. Traction forces mediated by N-cadherin were shown to be comparable to those sustained by ECM. The directional changes in predicted traction forces as a function of imposed loads (gel stiffness) provide the added evidence that N-cadherin is a mechanoresponsive adhesion receptor. Strikingly, the mechanical sensitivity response (gain) in terms of the measured cell-spread area as a function of imposed load (adhesive substrate rigidity) was consistently higher for N-cadherin-coated surfaces compared with ECM protein-coated surfaces. In addition, the cytoskeletal architecture of myocytes on an N-cadherin adhesive microenvironment was characteristically different from that on an ECM environment, suggesting that the two mechanotransductive cell adhesion systems may play both independent and complementary roles in myocyte cytoskeletal spatial organization. These results indicate that cell-to-cell-mediated force perception and transmission are involved in the organization and development of cardiac structure and function.",
"title": "Cardiac myocyte remodeling mediated by N-cadherin-dependent mechanosensing."
},
{
"docid": "7343711",
"text": "Successful cancer treatment requires understanding host immune response against tumor cells. PD-1 belongs to the CD28 superfamily of receptors that work as “checkpoints” of immune activation. PD-1 maintains immune self-tolerance to prevent autoimmunity and controls T-cell reaction during infection to prevent excessive tissue damage. Tumor cells that arise from normal tissue acquire mutations that can be targeted by lymphocytes. Accumulating lines of evidence suggest that tumor cells evade host immune attack by expressing physiological PD-1 ligands and stimulating PD-1 on the lymphocytes. Based on this idea, researchers have successfully demonstrated that systemic administration of monoclonal antibodies that inhibit the binding of PD-1 to the ligands reactivated T cells and augmented the anti-cancer immune response. In this review, I summarize the basics of T-cell biology and its regulation by PD-1 and discuss the current understanding and questions about this multifaceted molecule.",
"title": "Basics of PD-1 in self-tolerance, infection, and cancer immunity"
},
{
"docid": "3727986",
"text": "Cancer-associated fibroblasts (CAFs) promote tumour invasion and metastasis. We show that CAFs exert a physical force on cancer cells that enables their collective invasion. Force transmission is mediated by a heterophilic adhesion involving N-cadherin at the CAF membrane and E-cadherin at the cancer cell membrane. This adhesion is mechanically active; when subjected to force it triggers β-catenin recruitment and adhesion reinforcement dependent on α-catenin/vinculin interaction. Impairment of E-cadherin/N-cadherin adhesion abrogates the ability of CAFs to guide collective cell migration and blocks cancer cell invasion. N-cadherin also mediates repolarization of the CAFs away from the cancer cells. In parallel, nectins and afadin are recruited to the cancer cell/CAF interface and CAF repolarization is afadin dependent. Heterotypic junctions between CAFs and cancer cells are observed in patient-derived material. Together, our findings show that a mechanically active heterophilic adhesion between CAFs and cancer cells enables cooperative tumour invasion.",
"title": "A mechanically active heterotypic E-cadherin/N-cadherin adhesion enables fibroblasts to drive cancer cell invasion"
},
{
"docid": "26038789",
"text": "3BNC117 is a broad and potent neutralizing antibody to HIV-1 that targets the CD4 binding site on the viral envelope spike. When administered passively, this antibody can prevent infection in animal models and suppress viremia in HIV-1–infected individuals. Here we report that HIV-1 immunotherapy with a single injection of 3BNC117 affects host antibody responses in viremic individuals. In comparison to untreated controls that showed little change in their neutralizing activity over a 6-month period, 3BNC117 infusion significantly improved neutralizing responses to heterologous tier 2 viruses in nearly all study participants. We conclude that 3BNC117-mediated immunotherapy enhances host humoral immunity to HIV-1.",
"title": "HIV-1 therapy with monoclonal antibody 3BNC117 elicits host immune responses against HIV-1"
},
{
"docid": "4421578",
"text": "Characterization of human monoclonal antibodies is providing considerable insight into mechanisms of broad HIV-1 neutralization. Here we report an HIV-1 gp41 membrane-proximal external region (MPER)-specific antibody, named 10E8, which neutralizes ∼98% of tested viruses. An analysis of sera from 78 healthy HIV-1-infected donors demonstrated that 27% contained MPER-specific antibodies and 8% contained 10E8-like specificities. In contrast to other neutralizing MPER antibodies, 10E8 did not bind phospholipids, was not autoreactive, and bound cell-surface envelope. The structure of 10E8 in complex with the complete MPER revealed a site of vulnerability comprising a narrow stretch of highly conserved gp41-hydrophobic residues and a critical arginine or lysine just before the transmembrane region. Analysis of resistant HIV-1 variants confirmed the importance of these residues for neutralization. The highly conserved MPER is a target of potent, non-self-reactive neutralizing antibodies, suggesting that HIV-1 vaccines should aim to induce antibodies to this region of HIV-1 envelope glycoprotein.",
"title": "Broad and potent neutralization of HIV-1 by a gp41-specific human antibody"
},
{
"docid": "7177329",
"text": "Neutralizing antibodies are likely to play a crucial part in a preventative HIV-1 vaccine. Although efforts to elicit broadly cross-neutralizing (BCN) antibodies by vaccination have been unsuccessful, a minority of individuals naturally develop these antibodies after many years of infection. How such antibodies arise, and the role of viral evolution in shaping these responses, is unknown. Here we show, in two HIV-1–infected individuals who developed BCN antibodies targeting the glycan at Asn332 on the gp120 envelope, that this glycan was absent on the initial infecting virus. However, this BCN epitope evolved within 6 months, through immune escape from earlier strain-specific antibodies that resulted in a shift of a glycan to position 332. Both viruses that lacked the glycan at amino acid 332 were resistant to the Asn332-dependent BCN monoclonal antibody PGT128 (ref. 8), whereas escaped variants that acquired this glycan were sensitive. Analysis of large sequence and neutralization data sets showed the 332 glycan to be significantly under-represented in transmitted subtype C viruses compared to chronic viruses, with the absence of this glycan corresponding with resistance to PGT128. These findings highlight the dynamic interplay between early antibodies and viral escape in driving the evolution of conserved BCN antibody epitopes.",
"title": "Evolution of an HIV glycan–dependent broadly neutralizing antibody epitope through immune escape"
},
{
"docid": "5700349",
"text": "The morphology of neuronal dendritic spines is a critical indicator of synaptic function. It is regulated by several factors, including the intracellular actin/myosin cytoskeleton and transcellular N-cadherin adhesions. To examine the mechanical relationship between these molecular components, we performed quantitative live-imaging experiments in primary hippocampal neurons. We found that actin turnover and structural motility were lower in dendritic spines than in immature filopodia and increased upon expression of a nonadhesive N-cadherin mutant, resulting in an inverse relationship between spine motility and actin enrichment. Furthermore, the pharmacological stimulation of myosin II induced the rearward motion of actin structures in spines, showing that myosin II exerts tension on the actin network. Strikingly, the formation of stable, spine-like structures enriched in actin was induced at contacts between dendritic filopodia and N-cadherin-coated beads or micropatterns. Finally, computer simulations of actin dynamics mimicked various experimental conditions, pointing to the actin flow rate as an important parameter controlling actin enrichment in dendritic spines. Together these data demonstrate that a clutch-like mechanism between N-cadherin adhesions and the actin flow underlies the stabilization of dendritic filopodia into mature spines, a mechanism that may have important implications in synapse initiation, maturation, and plasticity in the developing brain.",
"title": "Mechanical coupling between transsynaptic N-cadherin adhesions and actin flow stabilizes dendritic spines"
},
{
"docid": "33904789",
"text": "Measurements of carcinoembryonic antigen (CEA) in blood increased dramatically in some patients who were receiving injections of monoclonal antibody. CEA titers were measured with a monoclonal antibody-based double-determinant enzyme immunoassay in which untreated plasma specimens were diluted with an equal volume of buffer containing mouse serum. Increasing CEA titers were accompanied by the appearance and coincident increase in titers of human antibody against mouse Ig (HAMA). Adsorption of these sera with solid-phase anti-human IgG or Protein A restored antigen titers to pretreatment values; evidently the serum factor eliciting false-positive CEA titers was most probably HAMA. Neither addition of undiluted mouse serum to the assay mixture nor pretreatment by heating plasma specimens to 70 degrees C effectively abolished HAMA interference. By contrast, protein precipitation with polyethylene glycol (130 g/L) or heating plasma samples to 90 degrees C eliminated false-positive titers caused by HAMA, but did not reduce authentic CEA titers.",
"title": "\"Sandwich\"-type immunoassay of carcinoembryonic antigen in patients receiving murine monoclonal antibodies for diagnosis and therapy."
},
{
"docid": "27907205",
"text": "A monoclonal antibody was raised against cells from an experimental rat myelocytic leukemia (BNML). The major characteristics of the rat leukemia model resemble those of human acute myelocytic leukemia. The monoclonal antibody (MCA) RM124 was characterized with respect to its labeling pattern of BNML leukemia cells, normal rat bone marrow cells, and the hemopoietic stem cell (HSC), by flow cytometric methods and complement-dependent cytotoxicity assays. Flow cytometry revealed a much higher labeling of the leukemic cells by the MCA-RM124 compared with normal bone marrow cells, including CFU-S and CFU-C. Only a subpopulation of the normal granulocytes showed cross reactivity, however, at a lower labeling density. On using the cytotoxicity assays, it was evident that there was a selective killing of leukemic cells as compared with the activity towards the normal hemopoietic stem cells (CFU-S).",
"title": "Characteristics of a monoclonal antibody (RM124) against acute myelocytic leukemia cells."
},
{
"docid": "46266579",
"text": "BACKGROUND The amyloid fibril deposits that cause systemic amyloidosis always contain the nonfibrillar normal plasma protein, serum amyloid P component (SAP). The drug (R)-1-[6-[(R)-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid (CPHPC) efficiently depletes SAP from the plasma but leaves some SAP in amyloid deposits that can be specifically targeted by therapeutic IgG anti-SAP antibodies. In murine amyloid A type amyloidosis, the binding of these antibodies to the residual SAP in amyloid deposits activates complement and triggers the rapid clearance of amyloid by macrophage-derived multinucleated giant cells. METHODS We conducted an open-label, single-dose-escalation, phase 1 trial involving 15 patients with systemic amyloidosis. After first using CPHPC to deplete circulating SAP, we infused a fully humanized monoclonal IgG1 anti-SAP antibody. Patients with clinical evidence of cardiac involvement were not included for safety reasons. Organ function, inflammatory markers, and amyloid load were monitored. RESULTS There were no serious adverse events. Infusion reactions occurred in some of the initial recipients of larger doses of antibody; reactions were reduced by slowing the infusion rate for later patients. At 6 weeks, patients who had received a sufficient dose of antibody in relation to their amyloid load had decreased liver stiffness, as measured with the use of transient elastography. These patients also had improvements in liver function in association with a substantial reduction in hepatic amyloid load, as shown by means of SAP scintigraphy and measurement of extracellular volume by magnetic resonance imaging. A reduction in kidney amyloid load and shrinkage of an amyloid-laden lymph node were also observed. CONCLUSIONS Treatment with CPHPC followed by an anti-SAP antibody safely triggered clearance of amyloid deposits from the liver and some other tissues. (Funded by GlaxoSmithKline; ClinicalTrials.gov number, NCT01777243.).",
"title": "Therapeutic Clearance of Amyloid by Antibodies to Serum Amyloid P Component."
},
{
"docid": "9600826",
"text": "Angiogenesis and cancer invasiveness greatly contribute to cancer malignancy. Arf6 and its effector, AMAP1, are frequently overexpressed in breast cancer, and constitute a central pathway to induce the invasion and metastasis. In this pathway, Arf6 is activated by EGFR via GEP100. Arf6 is highly expressed also in human umbilical vein endothelial cells (HUVECs) and is implicated in angiogenesis. Here, we found that HUVECs also highly express AMAP1, and that vascular endothelial growth factor receptor-2 (VEGFR2) recruits GEP100 to activate Arf6. AMAP1 functions by binding to cortactin in cancer invasion and metastasis. We demonstrate that the same GEP100-Arf6-AMAP1-cortactin pathway is essential for angiogenesis activities, including cell migration and tubular formation, as well as for the enhancement of cell permeability and VE-cadherin endocytosis of VEGF-stimulated HUVECs. Components of this pathway are highly expressed in pathologic angiogenesis, and blocking of this pathway effectively inhibits VEGF- or tumor-induced angiogenesis and choroidal neovascularization. The GEP100-Arf6-AMAP1-cortactin pathway, activated by receptor tyrosine kinases, appears to be common in angiogenesis and cancer invasion and metastasis, and provides their new therapeutic targets.",
"title": "GEP100-Arf6-AMAP1-Cortactin Pathway Frequently Used in Cancer Invasion Is Activated by VEGFR2 to Promote Angiogenesis"
},
{
"docid": "4340509",
"text": "Pattern formation of biological structures involves organizing different types of cells into a spatial configuration. In this study, we investigate the physical basis of biological patterning of the Drosophila retina in vivo. We demonstrate that E- and N-cadherins mediate apical adhesion between retina epithelial cells. Differential expression of N-cadherin within a sub-group of retinal cells (cone cells) causes them to form an overall shape that minimizes their surface contact with surrounding cells. The cells within this group, in both normal and experimentally manipulated conditions, pack together in the same way as soap bubbles do. The shaping of the cone cell group and packing of its components precisely imitate the physical tendency for surfaces to be minimized. Thus, simple patterned expression of N-cadherin results in a complex spatial pattern of cells owing to cellular surface mechanics.",
"title": "Surface mechanics mediate pattern formation in the developing retina"
}
] |
PLAIN-2533
|
PCBs in Children’s Fish Oil Supplements
|
[
{
"docid": "MED-2644",
"text": "Alkylphenols are widely used as plastic additives and surfactants. We report the identification of an alkylphenol, nonylphenol, as an estrogenic substance released from plastic centrifuge tubes. This compound was extracted with methanol, purified by flash chromatography and reverse-phase high performance liquid chromatography, and identified by gas chromatography-mass spectrometry. Nonylphenol induced both cell proliferation and progesterone receptor in human estrogen-sensitive MCF7 breast tumor cells. Nonylphenol also triggered mitotic activity in rat endometrium; this result confirms the reliability of the MCF7 cell proliferation bioassay. The estrogenic properties of alkylphenols, specifically nonylphenols, indicate that the use of plasticware containing these chemicals in experimental and diagnostic tests may lead to spurious results, and these compounds as well as alkylphenol polyethoxylates may also be potentially harmful to exposed humans and the environment at large.",
"title": "p-Nonyl-phenol: an estrogenic xenobiotic released from \"modified\" polystyrene."
},
{
"docid": "MED-2652",
"text": "The exposure to some chemicals can lead to hormone disrupting effects. Presently, much attention is focused on so-called xeno-estrogens, synthetic compounds that interact with hormone receptors causing a number of reactions that eventually lead to effects related to reproduction and development. The current study was initiated to investigate the presence of a number of such compounds in precipitation as a follow-up on a previous study in which pesticide concentrations in air and precipitation were determined. Rainwater samples were collected at about 50 locations in The Netherlands in a four week period. The samples were analysed for bisphenol-A, alkylphenols and alkylphenol ethoxylates, phthalates, flame retardants and synthetic musk compounds. The results clearly indicated the presence of these compounds in precipitation. The concentrations ranged from the low ng l(-1) range for flame retardants to several thousands of ng l(-1) for the phthalates. Bisphenol-A was found in 30% of the samples in concentrations up to 130 ng l(-1), while alkylphenols and alkylphenol ethoxylates were found in virtually all locations in concentrations up to 920 ng l(-1) for the individual compounds. Phthalates were by far the most abundant xeno-estrogens in the precipitation samples and were found in every sample. Di-isodecyl phthalate was found in a surprisingly high concentration of almost 100 000 ng l(-1). Polybrominated flame retardants were found in the low ng l(-1) range and generally in less than 20% of the samples. Noticeable was the finding of hexabromocyclododecane, a replacement for the polybrominted diphenyl ethers at one location in a concentration of almost 2000 ng l(-1). Finally, as expected, synthetic musk compounds were detected in almost all samples. This is especially true for the polycyclic musks HHCB and AHTN. Nitro musks were found, but only on a few locations. Kriging techniques were used to calculate precipitation concentrations in between actual sampling locations to produce contour plots for a number of compounds. These plots clearly show located emission sources for a number of compounds such as bisphenol-A, nonylphenol ethoxylate, phthalates and AHTN. On the contrary, the results for HHCB and some phthalates indicated diffuse emission patterns, probably as the result of the use of consumer products containing these compounds.",
"title": "Xeno-estrogenic compounds in precipitation."
},
{
"docid": "MED-2754",
"text": "BACKGROUND: Although previous randomized, double-blind, placebo-controlled trials reported the efficacy of omega-3 fatty acid supplements in the secondary prevention of cardiovascular disease (CVD), the evidence remains inconclusive. Using a meta-analysis, we investigated the efficacy of eicosapentaenoic acid and docosahexaenoic acid in the secondary prevention of CVD. METHODS: We searched PubMed, EMBASE, and the Cochrane Library in April 2011. Two of us independently reviewed and selected eligible randomized controlled trials. RESULTS: Of 1007 articles retrieved, 14 randomized, double-blind, placebo-controlled trials (involving 20 485 patients with a history of CVD) were included in the final analyses. Supplementation with omega-3 fatty acids did not reduce the risk of overall cardiovascular events (relative risk, 0.99; 95% CI, 0.89-1.09), all-cause mortality, sudden cardiac death, myocardial infarction, congestive heart failure, or transient ischemic attack and stroke. There was a small reduction in cardiovascular death (relative risk, 0.91; 95% CI, 0.84-0.99), which disappeared when we excluded a study with major methodological problems. Furthermore, no significant preventive effect was observed in subgroup analyses by the following: country location, inland or coastal geographic area, history of CVD, concomitant medication use, type of placebo material in the trial, methodological quality of the trial, duration of treatment, dosage of eicosapentaenoic acid or docosahexaenoic acid, or use of fish oil supplementation only as treatment. CONCLUSION: Our meta-analysis showed insufficient evidence of a secondary preventive effect of omega-3 fatty acid supplements against overall cardiovascular events among patients with a history of cardiovascular disease.",
"title": "Efficacy of omega-3 fatty acid supplements (eicosapentaenoic acid and docosahexaenoic acid) in the secondary prevention of cardiovascular disease: ..."
},
{
"docid": "MED-2655",
"text": "Background Broad dietary patterns have been linked to asthma but the relative contribution of specific nutrients is unclear. Soy genistein has important anti-inflammatory and other biological effects that might be beneficial in asthma. A positive association was previously reported between soy genistein intake and lung function but not with asthma exacerbations. Aims To conduct a post-hoc analysis of patients with inadequately controlled asthma enrolled in a prospective multicentre clinical trial to replicate this association. Methods A total of 300 study participants were included in the analysis. Dietary soy genistein intake was measured using the Block Soy Foods Screener. The level of soy genistein intake (little or no intake, moderate intake, or high intake) was compared with baseline lung function (pre-bronchodilator forced expiratory volume in 1 second (FEV1)) and asthma control (proportion of participants with an episode of poor asthma control (EPAC) and annualised rates of EPACs over a 6-month follow-up period. Results Participants with little or no genistein intake had a lower baseline FEV1 than those with a moderate or high intake (2.26L vs. 2.53L and 2.47L, respectively; p=0.01). EPACs were more common among those with no genistein intake than in those with a moderate or high intake (54% vs. 35% vs. 40%, respectively; p<0.001). These findings remained significant after adjustment for patient demographics and body mass index. Conclusions In patients with asthma, consumption of a diet with moderate to high amounts of soy genistein is associated with better lung function and better asthma control.",
"title": "Association of dietary soy genistein intake with lung function and asthma control: a post-hoc analysis of patients enrolled in a prospective multicentre clinical trial"
},
{
"docid": "MED-5072",
"text": "Antioxidant-rich diets are associated with reduced asthma prevalence. However, direct evidence that altering intake of antioxidant-rich foods affects asthma is lacking. The objective was to investigate changes in asthma and airway inflammation resulting from a low antioxidant diet and subsequent use of lycopene-rich treatments. Asthmatic adults (n=32) consumed a low antioxidant diet for 10 days, then commenced a randomized, cross-over trial involving 3 x 7 day treatment arms (placebo, tomato extract (45 mg lycopene/day) and tomato juice (45 mg lycopene/day)). With consumption of a low antioxidant diet, plasma carotenoid concentrations decreased, Asthma Control Score worsened, %FEV(1) and %FVC decreased and %sputum neutrophils increased. Treatment with both tomato juice and extract reduced airway neutrophil influx. Treatment with tomato extract also reduced sputum neutrophil elastase activity. In conclusion, dietary antioxidant consumption modifies clinical asthma outcomes. Changing dietary antioxidant intake may be contributing to rising asthma prevalence. Lycopene-rich supplements should be further investigated as a therapeutic intervention.",
"title": "Lycopene-rich treatments modify noneosinophilic airway inflammation in asthma: proof of concept."
},
{
"docid": "MED-2758",
"text": "Context Though multivitamins aim to prevent vitamin and mineral deficiency, there is a perception that multivitamins may prevent cardiovascular disease (CVD). Observational studies examining regular multivitamin use have been inconsistently associated with CVD, with no long-term clinical trials of multivitamin use. Objective To determine whether long-term multivitamin supplementation decreases the risk of major cardiovascular events among men. Design The Physicians' Health Study II is a randomized, double-blind, placebo-controlled trial of a common daily multivitamin, that began in 1997 with continued treatment and follow-up through June 1, 2011. Setting and Participants A total of 14,641 male U.S. physicians initially aged ≥50 years (mean [± SD] age; 64.3 [± 9.2] years), including 754 men with a history of CVD at randomization, were enrolled. Intervention Daily multivitamin, as Centrum Silver. Main Outcome Measures The primary cardiovascular outcome was a composite endpoint of major cardiovascular events, including nonfatal myocardial infarction (MI), nonfatal stroke, and fatal CVD. Secondary outcomes included MI and stroke individually. Results During a median (interquartile range) follow-up of 11.2 (10.7 to 13.3) years, there were 1,732 confirmed major cardiovascular events. Compared with placebo, there was no significant effect of a daily multivitamin on major cardiovascular events (active and placebo multivitamin groups, 11.0 and 10.8 events per 1,000 person-years; hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.91–1.10; P=0.91). Further, a daily multivitamin had no effect on total MI (active and placebo multivitamin groups, 3.9 and 4.2 events per 1,000 person-years; HR, 0.93; 95% CI, 0.80–1.09; P=0.39), total stroke (active and placebo multivitamin groups, 4.1 and 3.9 events per 1,000 person-years; HR, 1.06; 95% CI, 0.91–1.23; P=0.48), or cardiovascular mortality (active and placebo multivitamin groups, 5.0 and 5.1 events per 1,000 person-years; HR, 0.95; 95% CI, 0.83–1.09; P=0.47). A daily multivitamin was also not significantly associated with total mortality (HR, 0.94; 95% CI, 0.88–1.02; P=0.13). The effect of a daily multivitamin on major cardiovascular events did not differ between men with or without a baseline history of CVD (P, interaction = 0.62). Conclusions A daily multivitamin did not reduce major cardiovascular events, MI, stroke, and CVD mortality after more than a decade of treatment and follow-up.",
"title": "Multivitamins in the Prevention of Cardiovascular Disease in Men: The Physicians' Health Study II Randomized Controlled Trial"
},
{
"docid": "MED-2452",
"text": "A role for diet in the pathophysiology of asthma may be mediated by altered immune or antioxidant activity with consequent effects on airway inflammation. We evaluated associations between several dietary factors assessed by a semiquantitative food frequency questionnaire, and incidence of asthma over a 10-yr period in 77,866 women 34 to 68 yr of age. Women in the highest quintile of vitamin E intake from diet, but not from supplements, had a risk of 0.53 (95% confidence interval [CI] = 0.33 to 0.86) compared with women in the lowest quintile. This relationship, however, was attenuated when the contribution from nuts, a major source of vitamin E in these data and a possible allergen, was removed (relative risk = 0.74 [0.50 to 1.10], p for trend = 0.007). Positive associations were found for vitamins C and E from supplements, but appeared to be explained by women at high risk of asthma initiating use of vitamin supplements prior to diagnosis. A nonsignificant inverse association with carotene intake was noted, but no clear relations with asthma were demonstrated for intake of linoleic acid or omega-3 fatty acids. These data suggest that antioxidant supplementation and intake of various fats during adulthood are not important determinants of asthma, although vitamin E from diet may have a modest protective effect.",
"title": "A prospective study of diet and adult-onset asthma."
},
{
"docid": "MED-3034",
"text": "In the 1970s several states in the Great Lakes region became concerned about mercury contamination in lakes and rivers and were the first to issue local fish consumption advisories. In 2001, the Food and Drug Administration (FDA) advised pregnant women, nursing mothers, young children, and women who may become pregnant not to consume shark, swordfish, king mackerel, and tilefish and recommended that these women not exceed 12 ounces of other fish per week. In 2004, FDA reissued this advice jointly with the U.S. Environmental Protection Agency (EPA) and modified it slightly to provide information about consumption of canned tuna and more details about consumption of recreationally caught fish. Though several studies have examined consumers' awareness of the joint FDA and EPA advisory as well as different state advisories, few used representative data. We examined the changes in awareness and knowledge of mercury as a problem in fish using the pooled nationally representative 2001 and 2006 Food Safety Surveys (FSS) with sample sizes of 4482 in 2001 and 2275 in 2006. Our results indicated an increase in consumers' awareness of mercury as a problem in fish (69% in 2001 to 80% in 2006, p<.001). In our regression models, we found that in both years, parents having children less than 5 years of age were more aware of mercury in fish and knowledgeable about the information contained in the national advisories about mercury in fish (p<.01) than other adults. In both 2001 and 2006, women of childbearing age (aged 18-45) were less aware and knowledgeable about this information than other women. However, women of all age groups had larger gains in awareness and knowledge than their male counterparts during this time. Participants' race, education, income, region, fish preparation experiences, having a foodborne illness in the past year, and risk perceptions about the safety of food were significant predictors of their awareness and knowledge. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "Awareness and knowledge of methylmercury in fish in the United States."
},
{
"docid": "MED-2444",
"text": "This is a review of the side-effects of cyclosporin A (CyA) in patients with severe psoriasis; renal dysfunction and hypertension are discussed elsewhere. In particular, paraesthesia, hypertrichosis, gingival hyperplasia and gastrointestinal disorders may occur, but are generally transient, mild-to-moderate in severity and only rarely require discontinuation of CyA. Infections are not a problem. As expected with an immunosuppressive drug, there is the possible risk of tumour development, particularly squamous cell carcinomas. However, these skin malignancies developed almost exclusively in patients previously treated with PUVA and/or methotrexate. The few lymphoproliferative disorders regressed spontaneously on discontinuation of the drug. Whether the isolated cases of solid tumours were CyA-related is not known. Apart from a raised serum creatinine, an important indicator of renal dysfunction, the laboratory abnormalities included hypomagnesaemia, hyperkalaemia, increased uric acid, changes in liver function tests, and fluctuations in the serum cholesterol and triglyceride levels. Although most of these changes were not clinically relevant, laboratory monitoring of patients with psoriasis treated with CyA is essential.",
"title": "Side-effect profile of cyclosporin A in patients treated for psoriasis."
},
{
"docid": "MED-3021",
"text": "The hair-to-blood ratio and biological half-life of methylmercury in a one-compartment model seem to differ between past and recent studies. To reevaluate them, 27 healthy volunteers were exposed to methylmercury at the provisional tolerable weekly intake (3.4 µg/kg body weight/week) for adults through fish consumption for 14 weeks, followed by a 15-week washout period after the cessation of exposure. Blood was collected every 1 or 2 weeks, and hair was cut every 4 weeks. Total mercury (T-Hg) concentrations were analyzed in blood and hair. The T-Hg levels of blood and hair changed with time (p < 0.001). The mean concentrations increased from 6.7 ng/g at week 0 to 26.9 ng/g at week 14 in blood, and from 2.3 to 8.8 µg/g in hair. The mean hair-to-blood ratio after the adjustment for the time lag from blood to hair was 344 ± 54 (S.D.) for the entire period. The half-lives of T-Hg were calculated from raw data to be 94 ± 23 days for blood and 102 ± 31 days for hair, but the half-lives recalculated after subtracting the background levels from the raw data were 57 ± 18 and 64 ± 22 days, respectively. In conclusion, the hair-to-blood ratio of methylmercury, based on past studies, appears to be underestimated in light of recent studies. The crude half-life may be preferred rather than the recalculated one because of the practicability and uncertainties of the background level, though the latter half-life may approximate the conventional one.",
"title": "Hair-to-blood ratio and biological half-life of mercury: experimental study of methylmercury exposure through fish consumption in humans."
},
{
"docid": "MED-3026",
"text": "Background Prenatal exposure to mercury has been associated with adverse childhood neurologic outcomes in epidemiologic studies. Dose–response information for this relationship is useful for estimating benefits of reduced mercury exposure. Objectives We estimated a dose–response relationship between maternal mercury body burden and subsequent childhood decrements in intelligence quotient (IQ), using a Bayesian hierarchical model to integrate data from three epidemiologic studies. Methods Inputs to the model consist of dose–response coefficients from studies conducted in the Faroe Islands, New Zealand, and the Seychelles Islands. IQ coefficients were available from previous work for the latter two studies, and a coefficient for the Faroe Islands study was estimated from three IQ subtests. Other tests of cognition/achievement were included in the hierarchical model to obtain more accurate estimates of study-to-study and end point–to–end point variability. Results We find a central estimate of −0.18 IQ points (95% confidence interval, −0.378 to −0.009) for each parts per million increase of maternal hair mercury, similar to the estimates for both the Faroe Islands and Seychelles studies, and lower in magnitude than the estimate for the New Zealand study. Sensitivity analyses produce similar results, with the IQ coefficient central estimate ranging from −0.13 to −0.25. Conclusions IQ is a useful end point for estimating neurodevelopmental effects, but may not fully represent cognitive deficits associated with mercury exposure, and does not represent deficits related to attention and motor skills. Nevertheless, the integrated IQ coefficient provides a more robust description of the dose–response relationship for prenatal mercury exposure and cognitive functioning than results of any single study.",
"title": "Dose–Response Relationship of Prenatal Mercury Exposure and IQ: An Integrative Analysis of Epidemiologic Data"
},
{
"docid": "MED-2657",
"text": "BACKGROUND: Japanese cedar pollinosis, caused by the pollen of the Japanese cedar tree (Cryptomeria japonica), is the commonest seasonal allergic disease in Japan. A number of epidemiological surveys have been reported on Japanese cedar pollinosis, but it has never been assessed systematically or quantitatively. To confirm the increasing prevalence of Japanese cedar pollinosis and related factors, we conducted a meta-regression analysis on population-based surveys in Japan. METHODS: We searched for data from population-based surveys in which serological methods were used to test all participants. Weighted regression of logit-transformed prevalence and sensitization rates were used to evaluate the effects of the year of survey, age, and degree of urbanization. We also analyzed the relationship between prevalence and sensitization rate. RESULTS: Thirty-eight reports with 27 subgroups for prevalence and 134 subgroups for sensitization rate were selected from the literature published in the years between 1986 and 2000. The Japanese cedar pollen sensitization rate was found to be significantly correlated with the year of survey, age, and degree of urbanization (adjusted R(2) = 0.55). The coefficient for the correlation between the prevalence and the sensitization rate revealed a statistically significant correlation (Pearson's r = 0.70, p < 0.001). CONCLUSIONS: The prevalence of Japanese cedar pollinosis among adolescents was predicted to be 28.7% in metropolitan areas and 24.5% in the general population in urban areas in the year 2004, derived from the estimated sensitization rate and the relationship between sensitization rate and prevalence. The prevalence of Japanese cedar pollinosis increased 2.6-fold between 1980 and 2000, and the prevalence differed considerably according to age and degree of urbanization. Copyright (c) 2005 S. Karger AG, Basel",
"title": "Increasing prevalence of Japanese cedar pollinosis: a meta-regression analysis."
},
{
"docid": "MED-2479",
"text": "BACKGROUND: The prevalence of allergic diseases seems to have increased particularly over the past 35-40 years. Furthermore, allergic disease is less common among children in the formerly socialist countries of central and Eastern Europe as compared with Western Europe. It has been suggested that a reduced microbial stimulation during infancy and early childhood would result in a slower postnatal maturation of the immune system and development of an optimal balance between TH1- and TH2-like immunity. AIMS: To test the hypothesis that allergic disease among children may be associated with differences in their intestinal microflora in two countries with a low (Estonia) and a high (Sweden) prevalence of allergy. METHODS: From a prospective study of the development of allergy in relation to environmental factors, 29 Estonian and 33 Swedish 2-year-old children were selected. They were either nonallergic (n = 36) or had a confirmed diagnosis of allergy (n = 27) as verified by typical history and at least one positive skin prick test to egg or cow's milk. Weighed samples of faeces were serially diluted (10-2-10-9) and grown under anaerobic conditions. The counts of the various genera and species were calculated for each child. In addition, the relative amounts of the particular microbes were expressed as a proportion of the total count. RESULTS: The allergic children in Estonia and Sweden were less often colonized with lactobacilli (P < 0.01), as compared with the nonallergic children in the two countries. In contrast, the allergic children harboured higher counts of aerobic micro-organisms (P < 0. 05), particularly coliforms (P < 0.01) and Staphylococcus aureus (P < 0.05). The proportions of aerobic bacteria of the intestinal flora were also higher in the allergic children (P < 0.05), while the opposite was true for anaerobes (P < 0.05). Similarly, in the allergic children the proportions of coliforms were higher (P < 0. 05) and bacteroides lower (P < 0.05) than in the nonallergic children. CONCLUSIONS: Differences in the indigenous intestinal flora might affect the development and priming of the immune system in early childhood, similar to what has been shown in rodents. The role of intestinal microflora in relation to the development of infant immunity and the possible consequences for allergic diseases later in life requires further study, particularly as it would be readily available for intervention as a means for primary prevention of allergy by the administration of probiotic bacteria.",
"title": "The intestinal microflora in allergic Estonian and Swedish 2-year-old children."
},
{
"docid": "MED-1831",
"text": "In children, omega-3 polyunsaturated fatty acids (PUFAs) may elicit a suite of health benefits including enhancement of cognitive development. Subsequently, dietary supplements containing omega-3 PUFAs have become increasingly popular. Often, the largest source of beneficial PUFAs in these supplements is fish oil, which may contain significant levels of contaminants such as polychlorinated biphenyls (PCBs). The objectives of this study were to evaluate congener-specific PCB concentrations in 13 over-the-counter children's dietary supplements containing fish oils/powders and assess potential PCB exposures through ingestion of these products on a daily basis. Every supplement analysed contained PCBs, with a mean concentration of 9 ± 8 ng PCBs/g supplement. When following serving size suggestions, mean daily exposure values ranged from 2.5 to 50.3 ng PCBs/day. Daily exposures for children's supplements were significantly lower than those previously reported for adult supplements and may be explained, in part, by the variability in the amount of fish oil (and PUFA content) in a serving size. Based on this study, factors such as fish oil purification methods (e.g., molecular distillation) and the trophic level of the fish species used to make the fish oil cannot be used as indicators of PCB levels within children's supplements. Fish supplements may decrease or increase daily PCB exposure compared with ingestion of fresh fish. However, eating fish high in omega-3 PUFAs and low in PCBs may reduce PCB exposure compared with daily supplementation with fish oils for some products studied.",
"title": "Children's daily exposure to polychlorinated biphenyls from dietary supplements containing fish oils."
},
{
"docid": "MED-2464",
"text": "BACKGROUND: In recent decades, children's diet quality has changed and asthma prevalence has increased, although it remains unclear if these events are associated. OBJECTIVE: To examine children's total and component diet quality and asthma and airway hyperresponsiveness (AHR), a proxy for asthma severity. METHODS: Food frequency questionnaires adapted from the Nurses' Health Study and supplemented with foods whose nutrients which have garnered interest of late in relation to asthma were administered. From these data, diet quality scores (total and component), based on the Youth Healthy Eating Index (YHEI adapted) were developed. Asthma assessments were performed by pediatric allergists and classified by atopic status: Allergic asthma (≥1 positive skin prick test to common allergens >3 mm compared to negative control) versus non-allergic asthma (negative skin prick test). AHR was assessed via the Cockcroft technique. Participants included 270 boys (30% with asthma) and 206 girls (33% with asthma) involved in the 1995 Manitoba Prospective Cohort Study nested case-control study. Logistic regression was used to examine associations between diet quality and asthma, and multinomial logistic regression was used to examine associations between diet quality and AHR. RESULTS: Four hundred seventy six children (56.7% boys) were seen at 12.6 ± 0.5 years. Asthma and AHR prevalence were 26.2 and 53.8%, respectively. In fully adjusted models, high vegetable intake was protective against allergic asthma (OR 0.49; 95% CI 0.29-0.84; P < 0.009) and moderate/severe AHR (OR 0.58; 0.37-0.91; P < 0.019). CONCLUSIONS: Vegetable intake is inversely associated with allergic asthma and moderate/severe AHR. Copyright © 2012 Wiley Periodicals, Inc.",
"title": "Low vegetable intake is associated with allergic asthma and moderate-to-severe airway hyperresponsiveness."
},
{
"docid": "MED-2456",
"text": "Several studies have suggested that the increasing prevalence of symptoms of asthma, rhinitis and eczema, could be associated with dietary factors. In the present paper, a global analysis of prevalence rates of wheeze, allergic rhinoconjunctivitis and atopic eczema was performed in relation to diet, as defined by national food intake data. Analyses were based on the International Study of Asthma and Allergies in Childhood (ISAAC) data for 6-7 and 13-14 yr old children. Symptoms of wheeze, allergic rhinoconjunctivitis and atopic eczema symptom prevalence were regressed against per capita food intake, and adjusted for gross national product to account for economic development. Dietary data were based on 1995 Food and Agriculture Organisation of the United Nations data for 53 of the 56 countries that took part in ISAAC phase I (1994/1995). The 13-14 year age group showed a consistent pattern of decreases in symptoms of wheeze (current and severe), allergic rhinoconjunctivitis and atopic eczema, associated with increased per capita consumption of calories from cereal and rice, protein from cereals and nuts, starch, as well as vegetables and vegetable nutrients. The video questionnaire data for 13-14 yr olds and the ISAAC data for 6-7 yr olds showed similar patterns for these foods. A consistent inverse relationship was seen between prevalence rates of the three conditions and the intake of starch, cereals, and vegetables. If these findings could be generalised, and if the average daily consumption of these foods increased, it is speculated that an important decrease in symptom prevalence may be achieved.",
"title": "Diet and asthma, allergic rhinoconjunctivitis and atopic eczema symptom prevalence: an ecological analysis of the International Study of Asthma and..."
},
{
"docid": "MED-4365",
"text": "A myriad of health claims are being made in favor of the consumption of green tea. However, mostly due to the easy availability and greater than ever popularity of highly concentrated green tea extracts, sometimes combined with an attitude of more-is-better, certain health risks of green tea consumption have begun to emerge. Among such risks are the possibility of liver damage, the potential to interact with prescription drugs to alter their therapeutic efficacy, and the chance to cause harm when combined with other highly popular herbal remedies. This review will summarize documented examples of adverse effects of green tea in humans, and will discuss risks of copious consumption of highly concentrated green tea extracts as indicated by studies in animals. While there is no intention to minimize any of the scientifically established benefits of the use of green tea, the purpose of this review is to focus primarily on the potential for adverse effects and raise awareness of the rare, yet under-appreciated risks. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",
"title": "Adverse effects of concentrated green tea extracts."
},
{
"docid": "MED-3013",
"text": "A 2002 analysis documented $54.9 billion in annual costs of environmentally mediated diseases in US children. However, few important changes in federal policy have been implemented to prevent exposures to toxic chemicals. We therefore updated and expanded the previous analysis and found that the costs of lead poisoning, prenatal methylmercury exposure, childhood cancer, asthma, intellectual disability, autism, and attention deficit hyperactivity disorder were $76.6 billion in 2008. To prevent further increases in these costs, efforts are needed to institute premarket testing of new chemicals; conduct toxicity testing on chemicals already in use; reduce lead-based paint hazards; and curb mercury emissions from coal-fired power plants.",
"title": "Reducing the staggering costs of environmental disease in children, estimated at $76.6 billion in 2008."
},
{
"docid": "MED-1833",
"text": "BACKGROUND: Cod liver oil is an important source of vitamin D, but also contains other fat-soluble components such as vitamin A. Before 1999, the cod liver oil formula in Norway contained a high concentration of vitamin A (1000 µg per 5 ml). High vitamin A status is associated with increased risks of several chronic diseases. OBJECTIVE: To investigate the association between cod liver oil intake and asthma development. METHODS: In the Nord-Trøndelag Health Study, a total of 25 616 Norwegian adults aged 19-55 years were followed up from 1995-1997 to 2006-2008. Current analysis based on 17 528 subjects who were free of asthma and had complete information on cod liver oil intake at baseline. Cod liver oil intake was defined as daily intake ≥ 1 month during the year prior to baseline. Incident asthma was reported as new-onset asthma during the 11-year follow-up. RESULTS: Of the 17 528 subjects, 18% (n=3076) consumed cod liver oil daily for ≥ 1 month over the past year. Cod liver oil intake was significantly associated with incident asthma with an OR of 1.62 (95% CI 1.32 to 1.98) after adjustment for age, sex, daily smoking, physical activity, education, socio-economic status, family history of asthma, and body mass index (BMI). The positive association was consistent across age (< 40/≥ 40 years), sex (men/women), family history of asthma (yes/no) and BMI subgroups (< 25/≥ 25 kg/m(2)). CONCLUSIONS: Intake of cod liver oil with high vitamin A content was significantly associated with increased incidence of adult-onset asthma.",
"title": "Cod liver oil intake and incidence of asthma in Norwegian adults--the HUNT study."
},
{
"docid": "MED-3687",
"text": "This study was aimed at determining the probiotic potential of a large number of autochthonous lactic acid bacteria isolated from fruit and vegetables. Survival under simulated gastric and intestinal conditions showed that 35% of the strains, mainly belonging to the species Lactobacillus plantarum maintained high cell densities. Selected strains did not affect the immune-mediation by Caco-2 cells. All strains stimulated all 27 immune-mediators by peripheral blood mononuclear cells (PBMC). A significant (P<0.05; P<0.01) increase of the major part of cytokines and growth factors was found. A few chemokines were stimulated. Immune-mediators with pro-inflammatory activity (IL-17, EOTAXIN and IFNγ) were significantly (P<0.01) stimulated by all strains, followed by IL-1b>IP-10>IL-6>MIP1α. Stimulation of IL-12, IL-2 and IL-7 was strain dependent. Only a few strains increased the synthesis of cytokines with anti-inflammatory activity. Six L. plantarum strains were further selected. Four were defined as the strongly adhesive strains (more than 40 bacteria adhering to one Caco-2 cell), and 2 as the adhesive strains (5-40 bacteria adhering to one Caco-2 cell). Five strains grew and acidified chemically defined medium with fructo-oligosaccharides (FOS) as the only carbon source. End-products of FOS fermentation were found. All strains inhibited enterohemorragic Escherichia coli K12 and Bacillus megaterium F6 isolated from human sources. The results of this study showed that some autochthonous lactic acid bacteria from raw fruit and vegetables have functional features to be considered as novel probiotic candidates. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Novel probiotic candidates for humans isolated from raw fruits and vegetables."
},
{
"docid": "MED-2755",
"text": "A randomised controlled trial with a factorial design was done to examine the effects of dietary intervention in the secondary prevention of myocardial infarction (MI). 2033 men who had recovered from MI were allocated to receive or not to receive advice on each of three dietary factors: a reduction in fat intake and an increase in the ratio of polyunsaturated to saturated fat, an increase in fatty fish intake, and an increase in cereal fibre intake. The advice on fat was not associated with any difference in mortality, perhaps because it produced only a small reduction (3-4%) in serum cholesterol. The subjects advised to eat fatty fish had a 29% reduction in 2 year all-cause mortality compared with those not so advised. This effect, which was significant, was not altered by adjusting for ten potential confounding factors. Subjects given fibre advice had a slightly higher mortality than other subjects (not significant). The 2 year incidence of reinfarction plus death from ischaemic heart disease was not significantly affected by any of the dietary regimens. A modest intake of fatty fish (two or three portions per week) may reduce mortality in men who have recovered from MI.",
"title": "Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART)."
},
{
"docid": "MED-3019",
"text": "Background: Methylmercury (MeHg) is a known neuro-toxicant. Emerging evidence indicates it may have adverse effects on the neuro-logic and other body systems at common low levels of exposure. Impacts of MeHg exposure could vary by individual susceptibility or be confounded by bene-ficial nutrients in fish containing MeHg. Despite its global relevance, synthesis of the available literature on low-level MeHg exposure has been limited. Objectives: We undertook a synthesis of the current knowledge on the human health effects of low-level MeHg exposure to provide a basis for future research efforts, risk assessment, and exposure remediation policies worldwide. Data sources and extraction: We reviewed the published literature for original human epidemio-logic research articles that reported a direct biomarker of mercury exposure. To focus on high-quality studies and those specifically on low mercury exposure, we excluded case series, as well as studies of populations with unusually high fish consumption (e.g., the Seychelles), marine mammal consumption (e.g., the Faroe Islands, circumpolar, and other indigenous populations), or consumption of highly contaminated fish (e.g., gold-mining regions in the Amazon). Data synthesis: Recent evidence raises the possibility of effects of low-level MeHg exposure on fetal growth among susceptible subgroups and on infant growth in the first 2 years of life. Low-level effects of MeHg on neuro-logic outcomes may differ by age, sex, and timing of exposure. No clear pattern has been observed for cardio-vascular disease (CVD) risk across populations or for specific CVD end points. For the few studies evaluating immunologic effects associated with MeHg, results have been inconsistent. Conclusions: Studies targeted at identifying potential mechanisms of low-level MeHg effects and characterizing individual susceptibility, sexual dimorphism, and non-linearity in dose response would help guide future prevention, policy, and regulatory efforts surrounding MeHg exposure.",
"title": "Evidence on the Human Health Effects of Low-Level Methylmercury Exposure"
},
{
"docid": "MED-2662",
"text": "A human breast cancer cell line (MCF-7) was used to develop an in vitro screening assay for the detection of xenoestrogenic environmental pollutants. MCF-7 cells were cultured in DMEM containing 5% fetal bovine serum (FBS). An estrogenic response was defined as an increase in the frequency of proliferating MCF-7 cells, and was measured using a thymidine analog, bromodeoxyuridine, and flow cytometry. Di-2-ethylhexyl phthalate (DEHP) and 4-n-nonylphenol (4-n-NP) were used as model chemicals. The proliferation rate of S-phase cells after 24 h of exposure to various concentrations of 17beta-estradiol and to model compounds was compared with a positive and a negative control, containing 1 nM 17beta-estradiol and 0.1% ethanol, respectively. DEHP and 4-n-NP increased the frequency of proliferating MCF-7 cells in a dose-dependent manner. The lowest concentration that significantly increased the proliferation of MCF-7 cells was 10 microM for DEHP and 1 microM for 4-n-NP. The results showed that the assay is accurate and quick to perform. It may prove a valuable tool for screening potential estrogen-mimicking environmental pollutants.",
"title": "Effects of xenoestrogenic environmental pollutants on the proliferation of a human breast cancer cell line (MCF-7)."
},
{
"docid": "MED-3028",
"text": "OBJECTIVE The evidence on the association between fish consumption, dietary long-chain n-3 fatty acids, and risk of type 2 diabetes is inconsistent. We therefore performed a systematic review and meta-analysis of the available prospective evidence. RESEARCH DESIGN AND METHODS Studies were identified by searching the PubMed and EMBASE databases through 15 December 2011 and by reviewing the reference lists of retrieved articles. Prospective studies were included if they reported relative risk (RR) estimates with 95% CIs for the association between fish consumption and/or dietary long-chain n-3 fatty acids and incidence of type 2 diabetes. A dose-response random-effects model was used to combine study-specific RRs. Potential sources of heterogeneity were explored by prespecified stratifications. RESULTS Sixteen studies involving 527,441 participants and 24,082 diabetes cases were included. Considerable statistical heterogeneity in the overall summary estimates was partly explained by geographical differences. For each serving per week increment in fish consumption, the RRs (95% CIs) of type 2 diabetes were 1.05 (1.02–1.09), 1.03 (0.96–1.11), and 0.98 (0.97–1.00) combining U.S., European, and Asian/Australian studies, respectively. For each 0.30 g per day increment in long-chain n-3 fatty acids, the corresponding summary estimates were 1.17 (1.09–1.26), 0.98 (0.70–1.37), and 0.90 (0.82–0.98). CONCLUSIONS Results from this meta-analysis indicate differences between geographical regions in observed associations of fish consumption and dietary intake of long-chain n-3 fatty acids with risk of type 2 diabetes. In consideration of the heterogeneous results, the relationship warrants further investigation. Meanwhile, current public health recommendations on fish consumption should be upheld unchanged.",
"title": "Fish Consumption, Dietary Long-Chain n-3 Fatty Acids, and Risk of Type 2 Diabetes"
},
{
"docid": "MED-5092",
"text": "BACKGROUND: While there is a large body of data on the effects of long-chain polyunsaturated fatty acid supplementation of infant formula on visual and cognitive maturation during infancy, longterm visual and cognitive outcome data from randomized trials are scarce. AIM: To evaluate docosahexaenoic acid (DHA) and arachidonic acid (ARA)-supplementation of infant formula on visual and cognitive outcomes at 4 years of age. METHODS: Fifty-two of 79 healthy term infants who were enrolled in a single-center, double-blind, randomized clinical trial of DHA and ARA supplementation of infant formula were available for follow-up at 4 years of age. In addition, 32 breast-fed infants served as a \"gold standard\". Outcome measures were visual acuity and the Wechsler Preschool and Primary Scale of Intelligence--Revised. RESULTS: At 4 years, the control formula group had poorer visual acuity than the breast-fed group; the DHA- and DHA+ARA-supplemented groups did not differ significantly from the breast-fed group. The control formula and DHA-supplemented groups had Verbal IQ scores poorer than the breast-fed group. CONCLUSION: DHA and ARA-supplementation of infant formula supports visual acuity and IQ maturation similar to that of breast-fed infants.",
"title": "Visual acuity and cognitive outcomes at 4 years of age in a double-blind, randomized trial of long-chain polyunsaturated fatty acid-supplemented in..."
},
{
"docid": "MED-3023",
"text": "Exposure to methylmercury at any stage of central nervous system development could induce alterations and result in severe congenital abnormalities. Total mercury level in maternal hair during pregnancy correlates well with blood levels of methylmercury and with total mercury levels in fetal brain. A prospective study has been conducted and a total of 137 childbearing women living at the coastal region with term, normal pregnancies were included and their newborns evaluated by ultrasonography. Mothers and their newborns are divided in two groups according to their hair mercury levels; examined group with high body levels of mercury (≥ 1 μg/g) and control group with low body levels of mercury (<1 μg/g). Neurosonographic examination was conducted to all newborns. Two dimensions of cerebellum in the sagital-medial plane have been measured: maximum height and width starting from the roof of the fourth chamber. Majority of mothers had hair mercury levels lower than 1 μg/g (N = 107). Mean value was 0.88 μg/g (SD 1.24), ranging from 0.02 to 8.71 μg/g. There was no significant difference between the two groups when it comes to the width of cerebellum (Mann-Whitney test: Z = 1471; p = 0.141). However, comparison related to the length of cerebellum shows statistically significant smaller cerebellum in newborns whose mother had hair mercury levels higher than 1 μg/g (Mann-Whitney test: Z = 2329; p = 0.019). Our results lead to a conclusion that prenatal exposure to, what we consider to be, low-levels of methylmercury does influence fetal brain development detected as decreased size of newborn's cerebellum. From a clinical point of view, a question related to the influence of prenatal low-level methylmercury exposure on fetal neurodevelopment remains open. Our further objectives are to direct the research towards performing detailed neuropshychological tests on children at the age of 18 months. Such tests could indicate the presence of subtle neurological or neuropsychological deficits. Copyright © 2010 Elsevier Ltd. All rights reserved.",
"title": "Relationship between the prenatal exposure to low-level of mercury and the size of a newborn's cerebellum."
},
{
"docid": "MED-2643",
"text": "The incidence and/or prevalence of health problems associated with endocrine-disruption have increased. Many chemicals have endocrine-disrupting properties, including bisphenol A, some organochlorines, polybrominated flame retardants, perfluorinated substances, alkylphenols, phthalates, pesticides, polycyclic aromatic hydrocarbons, alkylphenols, solvents, and some household products including some cleaning products, air fresheners, hair dyes, cosmetics, and sunscreens. Even some metals were shown to have endocrine-disrupting properties. Many observations suggesting that endocrine disruptors do contribute to cancer, diabetes, obesity, the metabolic syndrome, and infertility are listed in this paper. An overview is presented of mechanisms contributing to endocrine disruption. Endocrine disruptors can act through classical nuclear receptors, but also through estrogen-related receptors, membrane-bound estrogen-receptors, and interaction with targets in the cytosol resulting in activation of the Src/Ras/Erk pathway or modulation of nitric oxide. In addition, changes in metabolism of endogenous hormones, cross-talk between genomic and nongenomic pathways, cross talk with estrogen receptors after binding on other receptors, interference with feedback regulation and neuroendocrine cells, changes in DNA methylation or histone modifications, and genomic instability by interference with the spindle figure can play a role. Also it was found that effects of receptor activation can differ in function of the ligand.",
"title": "Endocrine-Disrupting Chemicals: Associated Disorders and Mechanisms of Action"
},
{
"docid": "MED-3035",
"text": "Prenatal and early childhood exposure to methylmercury (MeHg) or polychlorinated biphenyls (PCBs) are associated with deficits in cognitive, sensory, motor and other functions measured by neurobehavioral tests. The main objective of this pilot study was to determine whether functional magnetic resonance imaging (fMRI) is effective for visualization of brain function alterations related to neurobehavior in subjects with high prenatal exposure to the two neurotoxicants, MeHg and PCBs. Twelve adolescents (all boys) from a Faroese birth cohort assembled in 1986–1987 were recruited based on their prenatal exposures to MeHg and PCB. All underwent fMRI scanning during behavioral tasks at age 15 years. Subjects with high mixed exposure to MeHg and PCBs were compared to those with low mixed exposure on fMRI photic stimulation and a motor task. Boys with low mixed exposures showed patterns of fMRI activation during visual and motor tasks that are typical of normal control subjects. However, those with high exposures showed activation in more areas of the brain and different and wider patterns of activation than the low mixed exposure group. The brain activation patterns observed in association with increased exposures to MeHg and PCBs are meaningful in regard to the known neurotoxicity of these substances. This methodology therefore has potential utility in visualizing structural neural system determinants of exposure-induced neurobehavioral dysfunction.",
"title": "Functional MRI approach to developmental methylmercury and polychlorinated biphenyl neurotoxicity"
},
{
"docid": "MED-2441",
"text": "Many patients with atopic dermatitis are dissatisfied with conventional treatments based on topical steroids and have experienced some traditional remedies and alternative therapies. However, most of such therapies have not been evaluated scientifically and clinically by specialists. This study was designed to assess whether a certain vegetarian diet might be effective for atopic dermatitis and if so, to identify the mechanisms of this remedy through analyses of immunological parameters. An open-trial study was carried out in twenty patients with atopic dermatitis. An improvement of dermatitis was evaluated by SCORAD index and serological and immunological parameters were monitored. After a two-month treatment, the severity of dermatitis was strikingly inhibited, as assessed by SCORAD index and serological parameters including LDH5 activity and a number of peripheral eosinophils. A sharp reduction in eosinophils and neutrophils was observed prior to improvement in the skin inflammation. In addition, PGE2 production by peripheral blood mononuclear cells was reduced by this treatment. In contrast, serum IgE levels did not change during the same period. Although this study is an open-trial one, it suggests that this treatment may be useful for the treatment of adult patients with severe atopic dermatitis.",
"title": "Vegetarian diet ameliorates symptoms of atopic dermatitis through reduction of the number of peripheral eosinophils and of PGE2 synthesis by monocy..."
},
{
"docid": "MED-2750",
"text": "OBJECTIVE: To see whether mortality among men with angina can be reduced by dietary advice. DESIGN: A randomized controlled factorial trial. SETTING: Male patients of general practitioners in south Wales. SUBJECTS: A total of 3114 men under 70 y of age with angina. INTERVENTIONS: Subjects were randomly allocated to four groups: (1) advised to eat two portions of oily fish each week, or to take three fish oil capsules daily; (2) advised to eat more fruit, vegetables and oats; (3) given both the above types of advice; and (4) given no specific dietary advice. Mortality was ascertained after 3-9 y. RESULTS: Compliance was better with the fish advice than with the fruit advice. All-cause mortality was not reduced by either form of advice, and no other effects were attributable to fruit advice. Risk of cardiac death was higher among subjects advised to take oily fish than among those not so advised; the adjusted hazard ratio was 1.26 (95% confidence interval 1.00, 1.58; P=0.047), and even greater for sudden cardiac death (1.54; 95% CI 1.06, 2.23; P=0.025). The excess risk was largely located among the subgroup given fish oil capsules. There was no evidence that it was due to interactions with medication. CONCLUSIONS: Advice to eat more fruit was poorly complied with and had no detectable effect on mortality. Men advised to eat oily fish, and particularly those supplied with fish oil capsules, had a higher risk of cardiac death. This result is unexplained; it may arise from risk compensation or some other effect on patients' or doctors' behaviour.",
"title": "Lack of benefit of dietary advice to men with angina: results of a controlled trial."
},
{
"docid": "MED-2448",
"text": "A double-blind comparative study was conducted on cedar pollinosis patients in order to evaluate the treatment efficacy of apple polyphenol (Ap). Ap was administered (500 mg) once daily for 12 weeks, starting about 2 weeks prior to cedar pollen dispersion. Pollinosis symptoms during the study were evaluated according to the classification in the guidelines for allergic rhinitis diagnosis and treatment. The results show that the sneezing score was significantly lower for the Ap group than with the placebo group during the early period of pollen dispersion and during the main dispersion period. In addition, no adverse reactions were induced by Ap during the study. These results suggest that Ap may alleviate the symptoms of cedar pollinosis.",
"title": "Clinical efficacy of apple polyphenol for treating cedar pollinosis."
},
{
"docid": "MED-2649",
"text": "Background Dietary fat exerts numerous complex effects on proinflammatory and immunologic pathways. Several epidemiological studies have examined the relationships between intake of fatty acids and/or foods high in fat and allergic rhinitis, but have provided conflicting findings. The current cross-sectional study investigated such relationships in Japan. Methods Study subjects were 1745 pregnant women. The definition of rhinoconjunctivitis was based on criteria from the International Study of Asthma and Allergies in Childhood. Information on dietary factors was collected using a validated self-administered diet history questionnaire. Adjustment was made for age; gestation; region of residence; number of older siblings; number of children; smoking; secondhand smoke exposure at home and at work; family history of asthma, atopic eczema, and allergic rhinitis; household income; education; and body mass index. Results The prevalence of rhinoconjunctivitis in the past 12 months was 25.9%. Higher meat intake was significantly associated with an increased prevalence of rhinoconjunctivitis: the adjusted odds ratio between extreme quartiles was 1.71 (95% confidence interval: 1.25-2.35, P for trend = 0.002). No measurable association was found between fish intake and rhinoconjunctivitis. Intake of total fat, saturated fatty acids, monounsaturated fatty acids, n-3 polyunsaturated fatty acids, α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, n-6 polyunsaturated fatty acids, linoleic acid, arachidonic acid, and cholesterol and the ratio of n-3 to n-6 polyunsaturated fatty acid intake were not evidently related to the prevalence of rhinoconjunctivitis. Conclusions The current results suggest that meat intake may be positively associated with the prevalence of rhinoconjunctivitis in young adult Japanese women.",
"title": "Dietary meat and fat intake and prevalence of rhinoconjunctivitis in pregnant Japanese women: baseline data from the Kyushu Okinawa Maternal and Child Health Study"
},
{
"docid": "MED-2661",
"text": "This paper presents the results of an investigation on the occurrence of alkylphenols (APs) and their ethoxylates (APEs) in 8 edible marine species from the Adriatic Sea and tries to estimate the corresponding intake for the Italian population. Two crustaceans, Nephrops norvegicus (Norway lobster) and Squilla mantis (spottail mantis shrimp), plus six fish species, Engraulis enchrascicolus (anchovy), Scomber scombrus (Atlantic mackerel), Merluccius merluccius (European hake), Mullus barbatus (red mullet), Solea vulgaris (common sole) and Lophius piscatorius (angler) were analyzed for their content of nonylphenol (NP), octylphenol (OP) and octylphenol polyethoxylates (OPEs). These compounds were found in all analysed samples. NP was detected at the highest concentrations: 118-399 and 9.5-1431 ng g(-1) fresh weight (fw) respectively in crustaceans and fish. OP was found at respective levels of 2.7-4.7 and 0.3-3.8 ng g(-1) fw in crustaceans and fish, whereas OPE was determined at respective concentrations of 1.2-16.8 and 0.2-21.1 ng g(-1) fw in the same species. These results, together with those from a previous study on 4 edible mollusc, allow to estimate respective daily intakes for NP, OP, and OPE of about 12, 0.1, and 0.1 microg day(-1) for an Italian adult living along the Adriatic Coast. In relation to NP and OP, these intakes are much lower than the doses associated with toxic effects in laboratory animals (9 mg kg(-1) bw for rats). Nevertheless, data of exposure from other sources to these chemicals and others with similar biological characteristics are needed.",
"title": "Alkylphenols and alkylphenol ethoxylates contamination of crustaceans and fishes from the Adriatic Sea (Italy)."
},
{
"docid": "MED-2646",
"text": "BACKGROUND: Certain foods may increase or decrease the risk of developing asthma, rhinoconjunctivitis and eczema. We explored the impact of the intake of types of food on these diseases in Phase Three of the International Study of Asthma and Allergies in Childhood. METHODS: Written questionnaires on the symptom prevalence of asthma, rhinoconjunctivitis and eczema and types and frequency of food intake over the past 12 months were completed by 13-14-year-old adolescents and by the parents/guardians of 6-7-year-old children. Prevalence ORs were estimated using logistic regression, adjusting for confounders, and using a random (mixed) effects model. RESULTS: For adolescents and children, a potential protective effect on severe asthma was associated with consumption of fruit ≥3 times per week (OR 0.89, 95% CI 0.82 to 0.97; OR 0.86, 95% CI 0.76 to 0.97, respectively). An increased risk of severe asthma in adolescents and children was associated with the consumption of fast food ≥3 times per week (OR 1.39, 95% CI 1.30 to 1.49; OR 1.27, 95% CI 1.13 to 1.42, respectively), as well as an increased risk of severe rhinoconjunctivitis and severe eczema. Similar patterns for both ages were observed for regional analyses, and were consistent with gender and affluence categories and with current symptoms of all three conditions. CONCLUSIONS: If the association between fast foods and the symptom prevalence of asthma, rhinoconjunctivitis and eczema is causal, then the findings have major public health significance owing to the rising consumption of fast foods globally.",
"title": "Do fast foods cause asthma, rhinoconjunctivitis and eczema? Global findings from the International Study of Asthma and Allergies in Childhood (ISAA..."
},
{
"docid": "MED-2762",
"text": "BACKGROUND: Vitamin and mineral supplements are commonly used to prevent chronic diseases. PURPOSE: To systematically review evidence for the benefit and harms of vitamin and mineral supplements in community-dwelling, nutrient-sufficient adults for the primary prevention of cardiovascular disease (CVD) and cancer. DATA SOURCES: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Database of s of Reviews of Effects were searched from January 2005 to 29 January 2013, with manual searches of reference lists and gray literature. STUDY SELECTION: Two investigators independently selected and reviewed fair- and good-quality trials for benefit and fair- and good-quality trials and observational studies for harms. DATA EXTRACTION: Dual quality assessments and data abstraction. DATA SYNTHESIS: Two large trials (n = 27 658) reported lower cancer incidence in men taking a multivitamin for more than 10 years (pooled unadjusted relative risk, 0.93 [95% CI, 0.87 to 0.99]). The study that included women showed no effect in that group. High-quality studies (k = 24; n = 324 653) of single and paired nutrients (such as vitamins A, C, or D; folic acid; selenium; or calcium) were scant and heterogeneous and showed no clear evidence of benefit or harm. Neither vitamin E nor β-carotene prevented CVD or cancer, and β-carotene increased lung cancer risk in smokers. LIMITATIONS: The analysis included only primary prevention studies in adults without known nutritional deficiencies. Studies were conducted in older individuals and included various supplements and doses under the set upper tolerable limits. Duration of most studies was less than 10 years. CONCLUSION: Limited evidence supports any benefit from vitamin and mineral supplementation for the prevention of cancer or CVD. Two trials found a small, borderline-significant benefit from multivitamin supplements on cancer in men only and no effect on CVD. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.",
"title": "Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer: An updated systematic evidence review for the U.S. ..."
},
{
"docid": "MED-2450",
"text": "Background Atopy is not uncommon among children living in rural Crete, but wheeze and rhinitis are rare. A study was undertaken to examine whether this discrepancy could be attributed to a high consumption of fresh fruit and vegetables or adherence to a traditional Mediterranean diet. Methods A cross‐sectional survey was performed in 690 children aged 7–18 years in rural Crete. Parents completed a questionnaire on their child's respiratory and allergic symptoms and a 58‐item food frequency questionnaire. Adherence to a Mediterranean diet was measured using a scale with 12 dietary items. Children underwent skin prick tests with 10 common aeroallergens. Results 80% of children ate fresh fruit (and 68% vegetables) at least twice a day. The intake of grapes, oranges, apples, and fresh tomatoes—the main local products in Crete—had no association with atopy but was protective for wheezing and rhinitis. A high consumption of nuts was found to be inversely associated with wheezing (OR 0.46; 95% CI 0.20 to 0.98), whereas margarine increased the risk of both wheeze (OR 2.19; 95% CI 1.01 to 4.82) and allergic rhinitis (OR 2.10; 95% CI 1.31 to 3.37). A high level of adherence to the Mediterranean diet was protective for allergic rhinitis (OR 0.34; 95% CI 0.18 to 0.64) while a more modest protection was observed for wheezing and atopy. Conclusion The results of this study suggest a beneficial effect of commonly consumed fruits, vegetables and nuts, and of a high adherence to a traditional Mediterranean diet during childhood on symptoms of asthma and rhinitis. Diet may explain the relative lack of allergic symptoms in this population.",
"title": "Protective effect of fruits, vegetables and the Mediterranean diet on asthma and allergies among children in Crete"
},
{
"docid": "MED-2757",
"text": "BACKGROUND: Multivitamins are the most commonly used supplement in the developed world. Recent epidemiologic findings suggest that multivitamin use increases the risk of mortality. OBJECTIVE: We aimed to determine whether multivitamin-multimineral treatment, used for primary or secondary prevention, increases the risk of mortality in independently living adults. DESIGN: We performed a meta-analysis of randomized controlled trials. Multiple electronic databases were systematically searched from March to October 2012. Randomized controlled primary or secondary prevention trials were considered for inclusion. Eligible trials investigated daily multivitamin-multimineral supplementation for ≥1 y. Cohorts described as institutionalized or as having terminal illness (tertiary prevention) were excluded. The number of deaths and the sample size of each study arm were extracted independently by 2 researchers. Twenty-one articles were included in the analysis, which generated a total pooled sample of 91,074 people and 8794 deaths. These trials were pooled in a meta-analysis, and the outcomes were expressed as RRs and 95% CIs. RESULTS: The average age of the pooled sample was 62 y, and the average duration of supplementation was 43 mo. Across all studies, no effect of multivitamin-multimineral treatment on all-cause mortality (RR: 0.98; 95% CI: 0.94, 1.02) was observed. There was a trend for a reduced risk of all-cause mortality across primary prevention trials (RR: 0.94; 95% CI: 0.89, 1.00). Multivitamin-multimineral treatment had no effect on mortality due to vascular causes (RR: 1.01; 95% CI: 0.93, 1.09) or cancer (RR: 0.96; 95% CI: 0.88, 1.04). No statistical evidence of heterogeneity or publication bias was observed. CONCLUSION: Multivitamin-multimineral treatment has no effect on mortality risk.",
"title": "Multivitamin-multimineral supplementation and mortality: a meta-analysis of randomized controlled trials."
},
{
"docid": "MED-2658",
"text": "The prevalence of allergic diseases has increased in recent decades. Allergic diseases, particularly asthma, are complex diseases with strong gene-environment interactions. Epidemiological studies have identified a variety of risk factors for the development of allergic diseases. Among them, endocrine-disrupting chemicals (EDCs) play an important role in triggering or exacerbating these diseases. 4-Nonylphenol (NP) and 4-octylphenol (OP)--two major alkylphenols--have been recognized as common toxic and xenobiotic endocrine disrupters. Due to their low solubility, high hydrophobicity, and low estrogenic activity, they tend to accumulate in the human body and may be associated with the adverse effects of allergic diseases. Recently, new evidence has supported the importance of alkylphenols in the in vitro allergic response. This review focuses on the effects of alkylphenols on several key cell types in the context of allergic inflammation. Copyright © 2012. Published by Elsevier B.V.",
"title": "Alkylphenols--potential modulators of the allergic response."
},
{
"docid": "MED-2455",
"text": "BACKGROUND: It has been postulated that dietary antioxidants may influence the expression of allergic diseases and asthma. To test this hypothesis a case-control study was performed, nested in a cross sectional study of a random sample of adults, to investigate the relationship between allergic disease and dietary antioxidants. METHODS: The study was performed in rural general practices in Grampian, Scotland. A validated dietary questionnaire was used to measure food intake of cases, defined, firstly, as people with seasonal allergic-type symptoms and, secondly, those with bronchial hyperreactivity confirmed by methacholine challenge, and of controls without allergic symptoms or bronchial reactivity. RESULTS: Cases with seasonal symptoms did not differ from controls except with respect to the presence of atopy and an increased risk of symptoms associated with the lowest intake of zinc. The lowest intakes of vitamin C and manganese were associated with more than fivefold increased risks of bronchial reactivity. Decreasing intakes of magnesium were also significantly associated with an increased risk of hyperreactivity. CONCLUSIONS: This study provides evidence that diet may have a modulatory effect on bronchial reactivity, and is consistent with the hypothesis that the observed reduction in antioxidant intake in the British diet over the last 25 years has been a factor in the increase in the prevalence of asthma over this period.",
"title": "Bronchial reactivity and dietary antioxidants"
},
{
"docid": "MED-2756",
"text": "BACKGROUND: Fish consumption and omega-3 polyunsaturated fatty acid (PUFA) intake are shown to protect from cardiovascular diseases (CVD). However, most fish contain environmental contaminants such as dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), and methylmercury (MeHg) that may have adverse effects on cardiovascular health. OBJECTIVE: Our aim was to elucidate the associations of fish consumption, omega-3 PUFAs, environmental contaminants with low-grade inflammation, early atherosclerosis, and traditional CVD risk factors. METHODS: The Health 2000 survey participants (n=1173) represented the general Finnish population and the Fishermen study participants (n=255) represented a population with high fish consumption and high exposure to environmental contaminants. Model-adjusted geometric means and tests for linear trend were calculated for CVD risk factors by tertiles of fish consumption and serum omega-3 PUFAs, and additionally in the Fishermen study only, by tertiles of serum PCDD/F+PCB, and blood MeHg. RESULTS: Serum triglyceride decreased across omega-3 PUFA tertiles in both sexes and studies. Insulin resistance, C-reactive protein, tumour necrosis factor α, and interleukin 6 decreased across omega-3 PUFA tertiles among the Health 2000 survey participants. Among the Fishermen study men, insulin resistance and arterial stiffness indicated by β-stiffness index tended to increase and the RR estimate for carotid artery plaque tended to decrease across tertiles of PCDD/F+PCB and MeHg. CONCLUSION: Previously established hypotriglyceridemic and anti-inflammatory effects of omega-3 PUFAs were seen also in this study. The hypothesised favourable effect on insulin sensitivity and arterial elasticity was suggested to be counteracted by high exposure to environmental contaminants but the effect on plaque prevalence appeared not to be harmful. Copyright © 2012 Elsevier Inc. All rights reserved.",
"title": "Fish consumption, omega-3 fatty acids, and environmental contaminants in relation to low-grade inflammation and early atherosclerosis."
},
{
"docid": "MED-2461",
"text": "This study aimed to evaluate the association of diet with respiratory symptoms and asthma in schoolchildren in Taipei, Taiwan. An in-class interview survey elicited experiences of asthma and respiratory symptoms and consumption frequencies of the major food categories in 2290 fifth graders. Respiratory symptoms surveyed included persistent cough, chest tightness, wheezing with cold, wheezing without cold, dyspnea-associated wheezing, and exercise-induced cough or wheezing. Results showed that the consumption of sweetened beverages had the strongest association with respiratory symptoms and was positively associated with six of the seven respiratory symptoms (all p < 0.05). The adjusted odds ratios (aOR) ranged from 1.05 (95% confidence interval (CI = 1.01-1.09) for exercise-induced cough to 1.09 (95% CI = 1.03-1.16) for wheezing without cold. Egg consumption was associated with 5 of the 7 respiratory symptoms. Consumptions of seafood, soy products, and fruits were each negatively associated with one of the seven respiratory symptoms (all p < 0.05). Consumption of seafood was negatively associated with physician-diagnosed asthma and consumptions of sweetened beverages and eggs were positively associated with suspected asthma (p < 0.05). In conclusion, the study suggests that diet is associated with the respiratory symptoms in schoolchildren in Taipei. Consumptions of sweetened beverages and eggs are associated with increased risk of respiratory symptoms and asthma whereas consumptions of soy products and fruits are associated with reduced risk of respiratory symptoms.",
"title": "The association of diet with respiratory symptoms and asthma in schoolchildren in Taipei, Taiwan."
},
{
"docid": "MED-2753",
"text": "The Diet and Reinfarction Trial (DART) involved 2033 men (mean age 56.5 years) recovering from myocardial infarction. They were randomly allocated to receive advice or to receive no advice on each of three dietary factors: an increase in fatty fish intake; a reduction in fat intake with an increase in polyunsaturated fat:saturated fat; an increased intake of cereal fibre. Compliance was satisfactory with the fish and fibre advice, but less so with the fat advice. The men given fish advice had 29% lower 2-year all-cause mortality; the other forms of advice did not have any significant effects. The Diet and Angina Randomized Trial (DART-2) involved 3114 men (mean age 61.1 years) with stable angina, who were followed up for 3-9 years. Advice to eat oily fish or take fish oil did not affect all-cause mortality, but it was associated with a significant increase in sudden cardiac death (P=0.018), and this effect was largely confined to the subgroup given fish oil capsules. Advice to eat more fruit and vegetables had no effect, probably because of poor compliance. The outcome of DART-2 appears to conflict with that of DART and some other studies; various possible explanations are considered. Nutritional interventions are not equally acceptable and should be tailored to the individuals for whom they are intended. Various distinct groups have a raised risk of CHD, and it cannot be assumed that the same nutritional interventions are appropriate to them all. Nutritional supplements do not necessarily have the same effects as the foods from which they are derived.",
"title": "Secondary prevention of CHD in UK men: the Diet and Reinfarction Trial and its sequel."
},
{
"docid": "MED-2469",
"text": "The intestinal flora is considered to have an impact on the development of the immune system. In the anthroposophic lifestyle, a diet comprising vegetables spontaneously fermented by lactobacilli, and a restrictive use of antibiotics, anti-pyretics and vaccinations, is typical. The aim of this study was to assess the gut flora in infants in relation to certain lifestyle characteristics associated with anthroposophy. Sixty-nine children < 2 years of age with an anthroposophic lifestyle, and 59 infants of a similar age with a traditional lifestyle, were clinically examined and questionnaire replies assessed. Fecal samples were analyzed by bacterial enumeration, bacterial typing through biochemical fingerprinting and by measuring microflora-associated characteristics (MACs). The numbers of colony-forming units (CFU)/g of feces were significantly higher for enterococci and lactic acid bacteria in children who had never been exposed to antibiotics (5.5 x 107 vs. 2.1 x 107; p < 0.001 and 10 x 107 vs. 4.1 x 107; p < 0.01, respectively). Furthermore, the number of enterococci was significantly higher in breastfed and vegetarian infants (p < 0.01). The diversity (Simpson's diversity index) of lactobacilli, as determined by biochemical fingerprinting, was higher in infants born at home than in those born in hospital (p < 0.01). Several MACs were related to specific lifestyle features, and infants with an anthroposophic lifestyle had a higher proportion of acetic acid and a lower proportion of propionic acid in their stool as compared to the control children. In conclusion, lifestyle factors related to the anthroposophic way of life influenced the composition of the gut flora in the infants. These differences may contribute to the lower prevalence of atopic disease previously observed in children in anthroposophic families.",
"title": "An anthroposophic lifestyle and intestinal microflora in infancy."
},
{
"docid": "MED-2459",
"text": "BACKGROUND: Free radical-mediated oxidative damage to lipids is thought to be an important process in the pathogenesis of atherosclerosis. Although previous studies have demonstrated a beneficial impact of antioxidant vitamin supplements on lipid peroxidation, the effect of dietary patterns on lipid peroxidation is unknown. METHODS AND RESULTS: During the 3-week run-in period of a randomized trial, 123 healthy individuals were fed a control diet, low in fruits, vegetables, and dairy products, with 37% of calories from fat. Participants were then randomized to consume for 8 weeks: (1) the control diet, (2) a diet rich in fruits and vegetables but otherwise similar to the control diet, and (3) a combination diet rich in fruits, vegetables, and low-fat dairy products and reduced in fat. Serum oxygen radical-absorbing capacity, malondialdehyde (an in vitro measure of lipid peroxidation), and breath ethane (an in vivo measure of lipid peroxidation) were measured at the end of run-in and intervention periods. Between run-in and intervention, mean (95% CI) change in oxygen radical-absorbing capacity (U/mL) was -35 (-93, 13) in the control diet, 26 (-15, 67) in the fruits and vegetables diet (P=0.06 compared with control), and 19 (-22, 54) in the combination diet (P=0.10 compared with control). Median (interquartile range) change in ethane was 0.84 (0.10, 1.59) in the control diet, 0.02 (-0.61, 0.83) in the fruits and vegetables diet (P=0.04 compared with control), and -1.00 (-1.97, 0.25) in the combination diet (P=0.005 compared with control). Change in malondialdehyde did not differ between diets. CONCLUSIONS: This study demonstrates that modification of diet can favorably affect serum antioxidant capacity and protect against lipid peroxidation.",
"title": "Effect of dietary patterns on measures of lipid peroxidation: results from a randomized clinical trial."
},
{
"docid": "MED-3030",
"text": "Consumption of marine fish provides both benefits (lean protein, omega-3 fatty acids and essential nutrients) and risks (main source of mercury (Hg) exposure for humans). Mercury is a potent neurotoxin and the source of more fish advisories nationwide than any other toxicant. Despite the widespread nature of Hg, it is unknown whether local Hg contamination reflects national and regional levels often used as bases to inform consumers of potential fish consumption risk. Thus, the objectives of our study were to examine Hg levels of six commonly consumed marine species harvested locally off the North Carolina coast and to compare our results to published regional (Monterey Bay Aquarium's Seafood Watch List) and national (Environmental Protection Agency, EPA, and Food and Drug Administration, FDA) Hg averages, action levels, and guidelines. We found significant differences in Hg concentrations among collected species, and we identified correlations between Hg concentration and fish length and trophic levels. Collected mahi mahi and triggerfish were below the EPA fish tissue action level (0.3ppm). Wahoo and grouper exceeded the EPA action level but were below the FDA action level (1.0ppm). King mackerel had the highest Hg concentration among targeted species, exceeding both EPA and FDA action levels. Further, our local results were not always consistent with calculated averages from EPA and FDA databases for the same species, and although many of our findings were consistent with Monterey Bay Aquarium's Seafood Watch List (southeast region), recommendations based on Hg levels would conflict with recommendations they provide based on sustainability. We find regional and national averages are not always reflective of local Hg contamination and suggest local data may be needed to accurately assess consumer risk.",
"title": "Do national advisories serve local consumers: an assessment of mercury in economically important North Carolina fish."
},
{
"docid": "MED-2759",
"text": "A commercial weight loss program with a client base composed of >95% women experienced sporadic complaints of nausea and vomiting after changing its multivitamin supplier. This retrospective and observational study was designed to determine if related adverse event reports were significant, and to investigate potential mechanism for their occurrence in this group of subjects, many of whom were concurrently receiving oral contraceptives or hormone replacement therapy. Incidence of nausea, vomiting, rash, and total complaints in the 3 months following the change of the multivitamin formulation was compared with the same complaints in the 3 months before the change. In the 3 months following the multivitamin change, there were 166 complaints of nausea and vomiting, 9 complaints of rash and 194 total complaints from a group of 88,468 patients. In the 3 months before the change in the multivitamin, there had been 2 complaints of nausea and vomiting, no complaints of rash, and 11 total complaints from 88,252 patients. The difference detected by a chi-squared test was significant for all events studied; nausea and vomiting (P < 0.0001), rash (P < 0.02), and total complaints (P < 0.0001). The altered multivitamins contained added citrus bioflavanoids not included in the original formula. Citrus bioflavanoids decrease the clearance of exogenous estrogens by inhibiting cytochrome P450 enzyme systems. Elevated estrogen levels could account for the increased incidence of nausea and vomiting. This experience demonstrates that adding dietary herbal supplements to multivitamins may be associated with adverse interactions with prescription drugs.",
"title": "Vomiting from multivitamins: a potential drug interaction."
},
{
"docid": "MED-2751",
"text": "Recent data on fishmeal and fish-oil supply are presented identifying key producer countries and raw material sources and distinguishing between whole fish and by-products. The conversion of these raw materials into marine ingredients is discussed and global volumes presented. This is followed by a summary of the main countries using these marine ingredients over recent years. Uses of fishmeal and fish-oil by market segment are then presented. From this, a global mass balance of inputs and outputs is derived which allows the calculation of the input-to-output ratios (fish in:fish out; FIFO) for the main aquaculture production types to be made. Current areas of focus by the industry include the need to demonstrate sustainable practice, more strategic use of marine ingredients, greater use of fishery and land-animal by-products as well as vegetable substitutes, and novel sources of essential omega-3 fats, notably the long-chain polyunsaturated fatty acids, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. Implications are drawn for future supply prospects of fishmeal and fish-oil and their future role in aquaculture, agriculture and human health. © 2013 The Fisheries Society of the British Isles.",
"title": "Global fishmeal and fish-oil supply: inputs, outputs and markets."
},
{
"docid": "MED-3027",
"text": "Background Some persistent environmental chemicals are suspected of causing an increased risk of type 2 diabetes mellitus, a disease particularly common after age 70. This concern was examined in a cross-sectional study of elderly subjects in a population with elevated contaminant exposures from seafood species high in the food chain. Methods Clinical examinations of 713 Faroese residents aged 70-74 years (64% of eligible population) included fasting plasma concentrations of glucose and insulin, and glycosylated hemoglobin. Lifetime exposure to persistent environmental chemicals from pilot whale and other traditional food was estimated from a dietary questionnaire and by analysis of blood samples for polychlorinated biphenyls (PCBs) and related food contaminants. Results Septuagenarians with type 2 diabetes or impaired fasting glycemia tended to have higher PCB concentrations and higher past intake of traditional foods, especially during childhood and adolescence. In non-diabetic subjects, the fasting insulin concentration decreased by 7% (95% CI= −12% to −2%) for each doubling of the PCB concentration after adjustment for sex and body mass index at age 20. Conversely, the fasting glucose concentration increased by 6% (−1% to 13%) for each doubling in PCB. Similar associations were seen in subjects without impaired fasting glycemia, while further adjustment for current body mass index and lipid metabolism parameters attenuated some of the associations. Conclusions Impaired insulin secretion appears to constitute an important part of the type 2 diabetes pathogenesis associated with exposure to persistent lipophilic food contaminants.",
"title": "Marine Food Pollutants as a Risk Factor for Hypoinsulinemia and Type 2 Diabetes"
},
{
"docid": "MED-1832",
"text": "The need for a dietary supply of docosahexaenoic acid (DHA) and arachidonic aid (AA) in term infants was evaluated in a double-masked randomized clinical trial of the effects of supplementation of term infant formula with DHA (0.35% of total fatty acids) or with DHA (0.36%) and AA (0.72%) on visual acuity development. One hundred and eight healthy term infants were enrolled in the study; 79 were exclusively formula-fed from birth (randomized group) and 29 were exclusively breast-fed (gold standard group). Infants were evaluated at four time points during the first 12 mo of life for blood fatty acid composition, growth, sweep visual evoked potential (VEP) acuity, and forced choice preferential looking acuity. Supplementation of term infant formula with DHA or with DHA and AA during the first 4 mo of life yields clear differences in total red blood cell (RBC) lipid composition. Supplementation of term infant formula with DHA or with DHA and AA also yields better sweep VEP acuity at 6, 17, and 52 wk of age but not at 26 wk of age, when acuity development reaches a plateau. The RBC lipid composition and sweep VEP acuity of supplemented infants was similar to that of human milk-fed infants, whereas the RBC lipid composition and sweep VEP acuity of unsupplemented infants was significantly different from human milk-fed infants. Differences in acuity among diet groups were too subtle to be detected by the forced choice preferential looking protocol. Infants in all diet groups had similar rates of growth and tolerated all diets well. Thus, early dietary intake of preformed DHA and AA appears necessary for optimal development of the brain and eye of the human infant.",
"title": "Visual acuity and the essentiality of docosahexaenoic acid and arachidonic acid in the diet of term infants."
},
{
"docid": "MED-3032",
"text": "Fish consumption during gestation can provide the fetus with long chain polyunsaturated fatty acids (LCPUFA) and other nutrients essential for growth and development of the brain. However, fish consumption also exposes the fetus to the neurotoxicant, methyl mercury (MeHg). We studied the association between these fetal exposures and early child development in the Seychelles Child Development Nutrition Study (SCDNS). Specifically, we examined a priori models of Ω-3 and Ω-6 LCPUFA measures in maternal serum to test the hypothesis that these LCPUFA families before or after adjusting for prenatal MeHg exposure would reveal associations with child development assessed by the BSID-II at ages 9 and 30 months. There were 229 children with complete outcome and covariate data available for analysis. At 9 months, the PDI was positively associated with total Ω-3 LCPUFA and negatively associated with the ratio of Ω-6/Ω-3 LCPUFA. These associations were stronger in models adjusted for prenatal MeHg exposure. Secondary models suggested that the MeHg effect at 9 months varied by the ratio of Ω-6/Ω-3 LCPUFA. There were no significant associations between LCPUFA measures and the PDI at 30 months. There were significant adverse associations, however, between prenatal MeHg and the 30 month PDI when the LCPUFA measures were included in the regression analysis. The BSID-II Mental Developmental Index (MDI) was not associated with any exposure variable. These data support the potential importance to child development of prenatal availability of Ω-3 LCPUFA present in fish and of LCPUFA in the overall diet. Furthermore, they indicate that the beneficial effects of LCPUFA can obscure the determination of adverse effects of prenatal MeHg exposure in longitudinal observational studies.",
"title": "Associations of maternal long chain polyunsaturated fatty acids, methyl mercury, and infant development in the Seychelles Child Development Nutrition Study"
},
{
"docid": "MED-2468",
"text": "BACKGROUND AND METHODS: We estimated the prevalence of self-reported asthma in adult Indians and examined several risk factors influencing disease prevalence. Analysis is based on 99 574 women and 56 742 men aged 20–49 years included in India’s third National Family Health Survey, 2005–2006. Multiple logistic regression analysis was used to estimate the prevalence odds ratios for asthma, adjusting for various risk factors. RESULTS: The prevalence of self-reported asthma was 1.8% (95%CI 1.6–2.0) among men and 1.9% (95%CI 1.8–2.0) among women, with higher rates in rural than in urban areas and marked geographic differences. After adjustment for known asthma risk factors, women were 1.2 times more likely to have asthma than men. Daily/weekly consumption of milk/milk products, green leafy vegetables and fruits were associated with a lower asthma risk, whereas consumption of chicken/meat, a lower body mass index (BMI; <16 kg/m2, OR 2.08, 95%CI 1.73–2.50) as well as a higher BMI (>30 kg/m2, OR 1.67, 95%CI 1.36–2.06), current tobacco smoking (OR 1.30, 95%CI 1.12–1.50) and ever use of alcohol (OR 1.21, 95%CI 1.05–1.39) were associated with an increased asthma risk. CONCLUSIONS: There are wide regional variations in the prevalence of asthma in India. With the exception of the findings for BMI, however, most of the associations of asthma with the risk factors are relatively weak and account for only a small proportion of cases. RÉSUMÉ CONTEXTE ET MÉTHODES: Nous avons estimé la prévalence auto-rapportée de l’asthme chez les Indiens adultes et examiné plusieurs facteurs de risque influençant la prévalence de la maladie. L’analyse repose sur 99 574 femmes et 56 742 hommes âgés de 20 à 49 ans et inclus dans la troisième Enquête Nationale des Familles en Inde, 2005–2006. On a utilisé l’analyse de régression logistique multiple pour estimer les odds ratio de prévalence pour l’asthme, après ajustement pour divers facteurs de risque. RÉSULTATS: La prévalence auto-rapportée de l’asthme est de 1,8% (IC95% 1,6–2,0) parmi les hommes et de 1,9% (IC95% 1,8–2,0) parmi les femmes, les taux étant plus élevés dans les zones rurales que dans les zones urbaines, et les différences géographiques étant marquées. Après ajustement pour les facteurs de risque d’asthme connus, les femmes sont 1,2 fois plus susceptibles de souffrir de l’asthme que les hommes. La consommation quotidienne ou hebdomadaire de lait/produits laitiers, de légumes à feuilles vertes et de fruits est en association avec un risque plus faible d’asthme alors que la consommation de poulet ou de viande, un index de masse corporelle (BMI) plus bas (<16 kg/m2, OR 2,08 ; IC95% 1,73–2,50) ainsi qu’un BMI plus élevé (>30 kg/m2, OR 1,67 ; IC95% 1,36–2,06), le fait de fumer du tabac actuellement (OR 1,30 ; IC95% 1,12–1,50) et l’utilisation de l’alcool à un moment quelconque (OR 1,21 ; IC95% 1,05–1,39) sont en association avec un risque accru d’asthme. La prévalence de l’asthme en Inde varie largement selon les régions. Toutefois, à l’exception des observations sur le BMI, l’association de l’asthme avec les facteurs de risque est relativement faible et ne rend compte que d’une petite proportion des cas seulement. RESUMEN MARCO DE REFERENCIA Y MÉTODOS: Se calculó la prevalencia de asma autorreferida en los adultos en la India y se evaluaron varios factores de riesgo que influyen sobre la prevalencia de la enfermedad. El estudio se basó en las 99 574 mujeres y los 56 742 hombres de 20 a 49 años de edad que participaron en la tercera Encuesta Nacional sobre la Salud de la Familia en la India entre el 2005 y el 2006. Mediante un análisis de regresión logística multifactorial se calculó la prevalencia de asma y el cociente de posibilidades de padecerla, al corregir diversos factores de riesgo. RESULTADOS: La prevalencia de asma autorreferida fue 1,8% en los hombres (intervalo de confianza [IC] del 95% 1,6 a 2,0) y 1,9% en las mujeres (IC95% 1,8 a 2,0); se observaron tasas más altas en las zonas rurales que en las zonas urbanas y se presentaron diferencias geográficas considerables. Tras corregir en función de algunos factores de riesgo de padecer asma conocidos, las mujeres presentaron una probabilidad 1,2 veces superior a los hombres de sufrir la enfermedad. El consumo diario o semanal de leche o productos lácteos, hortalizas de hojas verdes y frutas se asoció con un menor riesgo de asma y el consumo de carne de pollo o de res, un bajo índice de masa corporal (<16 kg/m2; OR 2,08; IC95% 1,73 a 2,50) igual que un alto índice de masa corporal (>30 kg/m2; OR 1,67; IC95% 1,36 a 2,06), el tabaquismo actual (OR 1,30; IC95% 1,12 a 1,50) y el consumo de alcohol en algún momento de la vida (OR 1,21; IC95% 1,05 a 1,39) se asociaron con un mayor riesgo de padecer la enfermedad. CONCLUSIÓN: Existen amplias variaciones geográficas en la prevalencia de asma en la India. Sin embargo, con la excepción del índice de masa corporal, la mayor parte de las asociaciones del asma con los factores de riesgo fueron débiles y explican solo una pequeña proporción de los casos.",
"title": "Prevalence and risk factors for self-reported asthma in an adult Indian population: a cross-sectional survey"
},
{
"docid": "MED-2472",
"text": "Thirty-five patients who had suffered from bronchial asthma for an average of 12 yr, all receiving long-term medication, 20 including cortisone, were subject to therapy with vegan food for 1 yr. In almost all cases, medication was withdrawn or drastically reduced. There was a significant decrease in asthma symptoms. Twenty-four patients (69%) fulfilled the treatment. Of these, 71% reported improvement at 4 months and 92% at 1 yr. There was a significant improvement in a number of clinical variables; for example, vital capacity, forced expiratory volume at one sec and physical working capacity, as well as a significant change in various biochemical indices as haptoglobin, IgM, IgE, cholesterol, and triglycerides in blood. Selected patients, with a fear of side-effects of medication, who are interested in alternative health care, might get well and replace conventional medication with this regimen.",
"title": "Vegan regimen with reduced medication in the treatment of bronchial asthma."
},
{
"docid": "MED-1834",
"text": "Observations of increasing allergy prevalence with decreasing distance from the Equator and positive associations with ambient ultraviolet radiation have contributed to a growing interest in the possible role of vitamin D in the etiology of allergy. The aims of this study were to describe any latitudinal variation in the prevalence of childhood allergy in Australia and to evaluate, in parallel, the individual associations between ultraviolet radiation (UVR)- and vitamin D-related measures and hayfever asthma and both conditions. Participants were population-based controls who took part in a multicenter case-control study, aged 18-61 yr and resident in one of four study regions ranging in latitude from 27°S to 43°S. Data were derived from a self-administered questionnaire, interview and examination by a research officer and biologic sampling. Latitude and longitude coordinates were geocoded from participants' residential locations and climatic data were linked to postcodes of current residence. Stored serum was analyzed for 25-hydroxyvitamin D concentrations and silicone rubber casts of the skin were used as an objective measure of cumulative actinic damage. There was an inverse latitude gradient for asthma (a 9% decrease per increasing degree of latitude); however, this pattern did not persist after adjusting for average daily temperature. There was no association between any of the UVR- or vitamin D-related measures and childhood asthma, but greater time in the sun in winter between the ages 6-15 yr was associated with an increase in the odds of having hayfever [adjusted odds ratios (OR) 1.29; 95% CI 1.01-1.63]. Oral supplementation with cod liver oil in childhood increased the odds of a history of having both asthma and hayfever (2.87; 1.00-8.32). Further investigation of the possible role of early vitamin D supplementation in the development of allergy is warranted. Our results also suggest that solar exposure during childhood may be important in allergic sensitization. Plausible explanations, including biologic mechanisms, exist for both observations. © 2010 John Wiley & Sons A/S.",
"title": "The role of latitude, ultraviolet radiation exposure and vitamin D in childhood asthma and hayfever: an Australian multicenter study."
},
{
"docid": "MED-3012",
"text": "The fish ingredient N3-docosahexaenoic acid 22:6 n-3 (DHA) stimulates brain development. On the other hand methylmercury (MeHg) in fish disturbs the developing central nervous system. In this Context the IQ score in children is considered as an aggregate measure of in utero brain development. To determine the effect of DHA exposure on prenatal neurodevelopment the maternal DHA intake during pregnancy was compared with its epidemiologically observed effect on the IQ score of children. For MeHg the maternal intake was converted into its accumulation in the maternal body. The maternal body burden then was compared with its epidemiologically observed relationship with the IQ score. Taking the MeHg and DHA content of 33 fish species the net effect of these compounds on the IQ score was quantified. For most fish species the adverse effect of MeHg on the IQ score exceeded the beneficial effect of DHA. In the case of long-living predators a negative effect up to 10 points on the IQ score was found. The results of this study indicate that food interventions aiming at the beneficial effects of fish consumption should focus on fish species with a high DHA content, while avoiding fish species with a high MeHg content. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Fish consumption during child bearing age: a quantitative risk-benefit analysis on neurodevelopment."
},
{
"docid": "MED-2760",
"text": "Context Multivitamin preparations are the most common dietary supplement, taken by at least one-third of all US adults. Limited observational studies have not provided evidence regarding associations of multivitamin use with total and site-specific cancer incidence or mortality. Objective To determine whether long-term multivitamin supplementation decreases the risk of total and site-specific cancer events among men. Design The Physicians’ Health Study II is a randomized, double-blind, placebo-controlled trial of a common multivitamin that began in 1997 with treatment and follow-up through June 1, 2011. Setting and Participants A total of 14,641 male U.S. physicians initially aged ≥50 years (mean [± SD] age; 64.3 [± 9.2] years), including 1,312 men with a history of cancer at randomization, were enrolled. Intervention Daily multivitamin, as Centrum Silver. Main Outcome Measures A primary outcome was total cancer (excluding non-melanoma skin cancer), with prostate, colorectal, and other site-specific cancers among secondary endpoints included in this report. Results During a median (interquartile range) follow-up of 11.2 (10.7 to 13.3) years, there were 2,669 men with confirmed cancer, including 1,373 cases of prostate cancer and 210 cases of colorectal cancer. Compared with placebo, men taking a daily multivitamin had a statistically significant reduction in the incidence of total cancer (active and placebo multivitamin groups, 17.0 and 18.3 events, respectively, per 1,000 person-years; hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.86–0.998; P=0.044). There was no significant effect of a daily multivitamin on prostate cancer (HR, 0.98; 95% CI, 0.88–1.09; P=0.76), colorectal cancer (HR, 0.89; 95% CI, 0.68–1.17; P=0.39), or other site-specific cancers There was a lower risk of cancer mortality that did not reach statistical significance (HR, 0.88; 95% CI, 0.77–1.01; P=0.07). Daily multivitamin use was associated with a reduction in total cancer among 1,312 men with a baseline history of cancer (HR, 0.73; 95% CI, 0.56–0.96; P=0.022), but this did not differ significantly from that among 13,329 men initially free of cancer (HR, 0.94; 95% CI, 0.87–1.02; P=0.15) (P, interaction = 0.07). Conclusions In this large prevention trial of male physicians, daily multivitamin supplementation modestly but significantly reduced the risk of total cancer.",
"title": "Multivitamins in the Prevention of Cancer in Men: The Physicians’ Health Study II Randomized Controlled Trial"
},
{
"docid": "MED-2442",
"text": "A few patients remain severely affected by atopic dermatitis into adult life despite treatment with systemic steroids, azathioprine, and photochemotherapy. 33 patients took part in a double-blind, placebo-controlled, crossover study to assess the efficacy and safety of cyclosporin (5 mg/kg per day) in adults with severe refractory atopic dermatitis. Treatments were given for eight weeks each with one group (n = 16) receiving placebo followed by cyclosporin and another (n = 17) receiving cyclosporin and then placebo. Disease activity, extent of disease, sleep and itch, topical steroid use, and adverse events were assessed every two weeks. Both extent and activity of dermatitis were significantly improved (p less than 0.001) as were subjective measures of disease. 20 patients receiving cyclosporin reported adverse events compared with 8 taking placebo, although no patient required withdrawal from the study. Cyclosporin therapy led to an increase in the mean serum urea, creatinine, and bilirubin concentrations, although only the rise in bilirubin was significant (p = 0.001). Our results confirm that cyclosporin is a safe and effective short-term treatment for severe, refractory atopic dermatitis.",
"title": "Double-blind, controlled, crossover study of cyclosporin in adults with severe refractory atopic dermatitis."
},
{
"docid": "MED-2656",
"text": "The aim of previous research into the causes of allergic diseases, including asthma was mostly to identify potential risk factors in the environment. No major risk factors have been identified, however. Over the past 10 years, focus has, therefore, more been directed towards protective factors that could enhance the development of tolerance to allergens which were previously encountered early in life, but are now lost in modern affluent societies. In particular, the role of childhood infections has been discussed, but so far these studies have not been conclusive. Recent epidemiological studies and experimental research suggest that the microbial environment and exposure to microbial products in infancy modifies immune responses and enhances the development of tolerance to ubiquitous allergens. The intestinal microflora may play a particular role in this respect, as it is the major external driving force in the maturation of the immune system after birth, and animal experiments have shown it to be a prerequisite for normal development of oral tolerance. Recent studies have shown differences in the composition of the microflora between healthy and allergic infants in countries with a high and low prevalence of allergies and between healthy and allergic infants within such countries. These differences are apparent within the first week of life and thus precede clinical symptoms. The use of live microorganisms that might be beneficial to health has a long tradition and the safety is well documented. Very recently, several prospective intervention studies, modifying the gut flora from birth have yielded encouraging results and may suggest a new mode of primary prevention of allergy in the future.",
"title": "Effects of intestinal microflora and the environment on the development of asthma and allergy."
},
{
"docid": "MED-3022",
"text": "Methylmercury (MM) is a very potent neurotoxic agent. Its role in polluting the environment is well documented. A vast amount of study over the past several decades has finally provided insight into many aspects of its effect. Exposure to MM may be through ingestion of poisoned fish or inadvertent misuse of grain treated with the poison as a fungicide. Major epidemics have occurred in Japan (Fetal Minamata disease), Iraq, Pakistan, Guatemala, and Ghana. Sporadic incidences have occurred in the United States and Canada. There is no effective antidote to counteract the effect of MM on the central nervous system, although the information documented should provide hope for more effective therapy in acute cases.",
"title": "The many faces of methylmercury poisoning."
},
{
"docid": "MED-2482",
"text": "Previous studies have suggested that probiotic administration may have therapeutic and/or preventive effects on atopic dermatitis in infants; however, its role in allergic airway diseases remains controversial. To determine whether daily supplementation with specific Lactobacillus gasseri A5 for 8 weeks can improve the clinical symptoms and immunoregulatory changes in school children suffering from asthma and allergic rhinitis (AR). We conducted a randomized, double-blind, placebo-controlled study on school children (age, 6-12 years) with asthma and AR. The eligible study subjects received either L. gasseri A5 (n = 49) or a placebo (n = 56) daily for 2 months. Pulmonary function tests were performed, and the clinical severity of asthma and AR was evaluated by the attending physicians in the study period. Diary cards with records of the day- and nighttime peak expiratory flow rates (PEFR), symptoms of asthma, and AR scores of the patients were used for measuring the outcome of the treatment. Immunological parameters such as the total IgE and cytokine production by the peripheral blood mononuclear cells (PBMCs) were determined before and after the probiotic treatments. Our results showed the pulmonary function and PEFR increased significantly, and the clinical symptom scores for asthma and AR decreased in the probiotic-treated patients as compared to the controls. Further, there was a significant reduction in the TNF-α, IFN-γ, IL-12, and IL-13 production by the PBMCs following the probiotic treatment. In conclusion, probiotic supplementation may have clinical benefits for school children suffering from allergic airway diseases such as asthma and AR.",
"title": "Randomized placebo-controlled trial of lactobacillus on asthmatic children with allergic rhinitis."
},
{
"docid": "MED-2474",
"text": "This ISAAC Phase Three synthesis provides summarised information on the main findings of the study, regional tables and figures related to the prevalence and severity of current symptoms of asthma, rhinoconjunctivitis and eczema in the main regions of the world. The large number of surveyed children (≈1,200,000), the large number of centres (233) and countries (98) that participated in ISAAC Phase Three makes this study the most comprehensive survey of these diseases ever undertaken. Globally, the prevalence for current asthma, rhinoconjunctivitis and eczema in the 13-14-year age group was 14.1%, 14.6% and 7.3%, respectively. In the 6-7-year age group the prevalence for current asthma, rhinoconjunctivitis and eczema was 11.7%, 8.5% and 7.9%, respectively. The study shows a wide variability in the prevalence and severity of asthma, rhinoconjunctivitis and eczema which occurs not just between regions and countries but between centres in the same country and centres in the same city. This study definitively establishes that the prevalence of those diseases can be very high in non-affluent centres with low socioeconomic conditions. The large variability also suggests a crucial role of local environment characteristics to determine the differences in prevalence between one place and another. Thus, ISAAC Phase Three has provided a large body of epidemiological information on asthma, rhinoconjunctivitis and eczema in childhood from contrasting environments which is expected to yield new clues about the aetiology of those conditions and reasons for their marked global variability. Copyright © 2012 SEICAP. Published by Elsevier Espana. All rights reserved.",
"title": "The International Study of Asthma and Allergies in Childhood (ISAAC) Phase Three: a global synthesis."
},
{
"docid": "MED-2449",
"text": "BACKGROUND: Recently, some common foods in daily life have been found to have anti-allergic effects. We have reported that tomato extract (TE) could possibly inhibit histamine release and mouse ear-swelling responses. Moreover, it is reported that TE could relieve the symptoms for Japanese cedar pollinosis. METHODS: To evaluate the anti-allergic effect of TE, we performed a randomized, double-blind, placebo-controlled study in 33 patients with perennial allergic rhinitis (PAR) using oral administration of TE (360 mg per day) or placebo for 8 weeks. RESULTS: We found that the sneezing score significantly decreased in the TE group at the end of the trial compared to the beginning (P < 0.05). There were decreasing tendencies of rhinorrhea and nasal obstruction in the TE group. The patients' quality of life was significantly improved in the TE group after 8 weeks of treatment (P < 0.05), but not in placebo group. A significant improvement in total symptom scores, combining sneezing, rhinorrhea and nasal obstruction, was observed after oral administration of TE for 8 weeks (P < 0.01). The safety of TE treatment was confirmed by laboratory tests and inspection of general conditions. CONCLUSIONS: TE can be expected to safely improve the nasal symptoms of PAR.",
"title": "An evaluation of the clinical efficacy of tomato extract for perennial allergic rhinitis."
},
{
"docid": "MED-2446",
"text": "BACKGROUND: Allergic diseases have risen in prevalence over recent decades. The aetiology remains unclear but is likely to be a result of changing lifestyle and/or environment. A reduction in antioxidant intake, consequent to reduced intake of fresh fruits and vegetables, has been suggested as a possible cause. OBJECTIVE: To investigate whether dietary antioxidant intake at age 5 was related to atopy at 5 and 8 years of age amongst children in an unselected birth cohort. METHODS: Children were followed from birth. Parents completed a validated respiratory questionnaire and children were skin prick tested at 5 and 8 years of age. Serum IgE levels were measured at age 5. At age 5, antioxidant intake was assessed using a semi-quantitative food frequency questionnaire (FFQ). A nutrient analysis program computed nutrient intake, and frequency counts of foods high in the antioxidant vitamins A, C and E were assessed. RESULTS: Eight hundred and sixty-one children completed both the respiratory and FFQ. Beta-carotene intake was associated with reduced risk of allergic sensitization at age 5 [0.80 (0.68-0.93)] and 8 [0.81 (0.70-0.94)]. In addition, beta-carotene intake was negatively associated with total IgE levels (P = 0.002). Vitamin E intake was associated with an increased risk of allergic sensitization [1.19 (1.02-1.39)], only at age 5. There was no association between antioxidant intakes and wheeze or eczema. CONCLUSION: Increased beta-carotene intake was associated with a reduced risk of allergic sensitization and lower IgE levels, in 5- and 8-year-old children. Dietary antioxidants may play a role in the development of allergic sensitization.",
"title": "Dietary antioxidant intake, allergic sensitization and allergic diseases in young children."
},
{
"docid": "MED-2659",
"text": "U.S. and European regulators and researchers disagree over risks of a common class of surfactants.",
"title": "European bans on surfactant trigger transatlantic debate."
},
{
"docid": "MED-4366",
"text": "BACKGROUND: Many different dietary supplements are being sold in North America. The quality of the evidence supporting their efficacy covers a wide spectrum: Some are based on solid science (such as vitamin D and fish oil), whereas with most supplements there is little or no supporting evidence. Types of supplements commonly sold include exotic fruit juices (such as goji juice) and single herbs or mixture of herbs. Common claims made in support of particular supplements are that they are rich in antioxidants, induce detoxification, stimulate the immune system, and cause weight loss. Supplements are commonly sold through health food stores and by multilevel marketing. Sales may be promoted using bulk mail (\"junk mail\"), spam e-mails, and Web sites. A large part of marketing is based on claims that are blatantly dishonest. CONCLUSIONS: Whereas supplements for which good supporting evidence exists generally cost around $3-$4 per month, those that are heavily promoted for which there is little supporting evidence cost about $20-$60 per month. The major cause of this problem in the United States is weakness of the law. There is an urgent need for stricter regulation and for giving better advice to the general public.",
"title": "The marketing of dietary supplements in North America: the emperor is (almost) naked."
},
{
"docid": "MED-2453",
"text": "BACKGROUND: Fresh fruit consumption and vitamin C intake have been associated with improved lung function in adults. Whether this is due to enhancement of lung growth, to a reduction in lung function decline, or to protection against bronchospasm is unclear. METHODS: In a cross- sectional school based survey of 2650 children aged 8-11 from 10 towns in England and Wales the main outcome measure was forced expiratory volume in one second (FEV1) standardised for body size and sex. Exposure was assessed by a food frequency questionnaire to parents and by measurement of plasma levels of vitamin C in a subsample of 278 children. RESULTS: FEV1 was positively associated with frequency of fresh fruit consumption. After adjustment for possible confounding variables including social class and passive smoking, those who never ate any fresh fruit had an estimated FEV1 some 79 ml (4.3%) lower than those who ate these items more than once a day (95% CI 22 to 136 ml). The association between FEV1 and fruit consumption was stronger in subjects with wheeze than in non-wheezers (p = 0.020 for difference in trend), though wheeze itself was not related to fresh fruit consumption. Frequency of consumption of salads and of green vegetables were both associated with FEV1 but the relationships were weaker than for fresh fruit. Plasma vitamin C levels were unrelated to FEV1 (r = - 0.01, p = 0.92) or to wheeze and were only weakly related to fresh fruit consumption (r = 0.13, p = 0.055). CONCLUSIONS: Fresh fruit consumption appears to have a beneficial effect on lung function in children. Further work is needed to confirm whether the effect is restricted to subjects who wheeze and to identify the specific nutrient involved.",
"title": "Effect of fresh fruit consumption on lung function and wheeze in children"
},
{
"docid": "MED-2476",
"text": "An increase in asthma and atopic disease has been recorded in many countries where society has become more prosperous. We have investigated two possible explanations: a reduction in childhood infections and a change in diet. In a cohort of people followed up since 1964, originally selected as a random sample of primary school children, we have investigated the relevance of family size and the common childhood infectious diseases to development of eczema, hay fever and asthma. Although membership of a large family reduced risks of hay fever and eczema (but not asthma), this was not explained by the infections the child had suffered. Indeed, the more infections the child had had, the greater the likelihood of asthma, although measles gave a modest measure of protection. We have investigated dietary factors in two separate studies. In the first, we have shown the risks of bronchial hyper-reactivity are increased seven-fold among those with the lowest intake of vitamin C, while the lowest intake of saturated fats gave a 10-fold protection. In the second, we have shown that the risk of adult-onset wheezy illness is increased five-fold by the lowest intake of vitamin E and doubled by the lowest intake of vitamin C. These results were supported by direct measurements of the vitamins and triglycerides in plasma. We have proposed that changes in the diet of pregnant women may have reflected those observed in the population as a whole and that these may have resulted in the birth of cohorts of children predisposed to atopy and asthma. The direct test of this is to study the diet and nutritional status of a large cohort of pregnant women and to follow their offspring forward. This is our current research.",
"title": "Diet, infection and wheezy illness: lessons from adults."
},
{
"docid": "MED-2475",
"text": "Current understanding of the use of exclusion diets in the management of asthma in children is limited and controversial. The aim of this study was to examine the effects of excluding eggs and milk on the occurrence of symptoms in children with asthma and involved 22 children aged between three and 14 years clinically diagnosed as having mild to moderate disease. The investigation was single blind and prospective, and parents were given the option of volunteering to join the 'experiment' group, avoiding eggs, milk and their products for eight weeks, or the 'control' group, who consumed their customary food. Thirteen children were recruited to the experimental group and nine to the control group. A trained paediatrician at the beginning and end of the study period assessed the children. A seven-day assessment of food intake was made before, during and immediately after the period of dietary intervention in both groups. A blood sample was taken from each child for determination of food specific antibodies and in those children who could do so, the peak expiratory flow rate (PEFR) was measured. Based on the recommended nutrient intake (RNI), the mean percentage energy intake of the children in the experimental group was significantly lower (p < 0.05) in the experimental group. After the eight-week study period and compared with baseline values, the mean serum anti-ovalbumin IgG and anti-beta lactoglobulin IgG concentrations were statistically significantly reduced (p < 0.05) for both in the experimental group. In contrast, the values for anti-ovalbumin IgG in the control group were significantly increased and those for anti-beta lactoglobulin IgG were practically unchanged. The total IgE values were unchanged in both groups. Over the study period, the PEFR in those children in the experimental group able to perform the test was significantly increased, but no such change was noted in the children in the control group who could do the test. These results suggest that even over the short time period of eight weeks, an egg- and milk-free diet can reduce atopic symptoms and improve lung function in asthmatic children.",
"title": "The effects of exclusion of dietary egg and milk in the management of asthmatic children: a pilot study."
},
{
"docid": "MED-3025",
"text": "Detailed clinical and neuropathological studies have been made in two fullterm newborn human infants who were exposed to methylmercury in utero as a result of maternal ingestion of methylmercury-contaminated bread in early phases of pregnancy. High levels of mercury were detected in various regions of the brain at autopsy. Study of the brains revealed a disturbance in the development in both cases, consisting essentially of an incomplete or abnormal migration of neurons to the cerebellar and cerebral cortices, and deranged cortical organization of the cerebrum. There were numerous heterotopic neurons, both isolated and in groups, in the white matter of cerebrum and cerebellum and the laminar cortical pattern of the laminar cortical pattern of the cerebrum was disturbed in many regions as was shown by the irregular groupings and the deranged alignment of cortical. Prominent in the white matter of the cerebrum and the cerebellum was diffuse gemistocytic astrocytosis accompanied by an accumulation of mercury grains in their cytoplasm. These findings indicate a high degree of vulnerability of human fetal brain to maternal intoxication by methylmercury. A major effect appears to be related to faulty development and not to destructive focal neuronal damage as has been observed in mercury intoxicaiton in adults and children exposed postnatally.",
"title": "Abnormal neuronal migration, deranged cerebral cortical organization, and diffuse white matter astrocytosis of human fetal brain: a major effect of..."
},
{
"docid": "MED-2761",
"text": "PURPOSE: The aim of this study was to examine the prevalence of self-reported multivitamin use in the Physicians' Health Study (PHS) cohort and its association with various lifestyle, clinical, and dietary factors to improve our understanding of who tends to use multivitamins. METHODS: Among 18,040 middle-aged and older men, information on lifestyle and clinical factors was collected from a baseline enrollment questionnaire, and supplement use and dietary factors were assessed through a food-frequency questionnaire. Four categories of multivitamin use were considered: (1) no supplement use, (2) use of multivitamins only, (3) use of multivitamins with other individual vitamin/mineral supplements, and (4) use of other supplements only. We used logistic regression to calculate multivariate odds ratios and 95% confidence intervals of taking multivitamin supplements for various lifestyle, clinical and dietary factors. RESULTS: Overall, 36% of men reported current multivitamin use. Men who were older, current smokers, and currently using aspirin were 143, 43, and 74% more likely to use multivitamins only. Men having a history of hypercholesterolemia were 16% more likely to use multivitamins only. A 14, 24, and 26% greater likelihood of using multivitamins was also observed among men consuming more fruits and vegetables, whole grains, and tea, respectively. Similar associations were observed for the likelihood of using multivitamins with other supplements; however, men with higher physical activity, history of cancer, hypertension, higher consumption of nuts, and lower consumption of red meat and coffee were also more likely to use multivitamins with other supplements (all P < 0.05). CONCLUSION: Self-reported multivitamin use associated with lifestyle, clinical and dietary factors may be an indicator of healthy behaviors. These results provide important information for the interpretation of the recent findings from the PHS II trial and consideration of results from observational studies of multivitamin use and chronic disease.",
"title": "Who uses multivitamins? A cross-sectional study in the Physicians' Health Study."
},
{
"docid": "MED-2445",
"text": "Allergic disorders encompass skin, food and respiratory allergies. Sensitization to a normally harmless allergen results in the immune system being biased to a predominant T-helper type 2 response. Re-exposure to the same allergen leads to a robust secretion of allergy-related mediators that eventually triggers symptoms. Our understanding of these disorders has enabled the search of therapeutic approaches that can either modulate the sensitization process or impact on allergic mediators, thus helping manage allergic symptoms. Polyphenols are one such class of compounds that are found in foods and plant sources and have been investigated for their anti-allergic effect in different disease models and in human clinical trials. Their anti-inflammatory profile is known to impact on the recruitment of immune cells to the skin and in preventing the development of secondary infections following disruption of the skin barrier. The interaction of polyphenols with proteins can modulate the process of allergic sensitization and their direct effect on allergic effector cells such as mast cells inhibit mediator release, resulting in the alleviation of symptoms. In addition, their endogenous anti-oxidant ability limits the extent of cellular injury from free radicals during the allergic insult. Overall, polyphenols hold promise as anti-allergy agents capable of influencing multiple biological pathways and immune cell functions in the allergic immune response and deserve further investigation. The objective of the current review is to summarize the key findings and progress made in studying polyphenols as anti-allergic ingredients. Special emphasis is placed in this review to highlight key physiological, cellular and signalling pathways implicated in the mechanism of action of different polyphenols in the context of allergic disorders and their manifestations. © 2011 Blackwell Publishing Ltd.",
"title": "Dietary polyphenols in the prevention and treatment of allergic diseases."
},
{
"docid": "MED-2460",
"text": "BACKGROUND: Elevated oxidative stress and impaired antioxidant defences are increasingly recognised features of asthma. Carotenoids are potent dietary antioxidants that may protect against asthma by reducing oxidative damage. OBJECTIVES: This study aimed firstly, to characterise circulating and airway levels of carotenoids in asthma compared to healthy controls, in relation to dietary intake. Secondly, the study aimed to test whether airway lycopene defences can be improved using oral supplements. METHODS: Induced sputum and peripheral blood samples were collected from subjects with asthma (n = 15) and healthy controls (n = 16). Dietary carotenoid intakes were estimated using the 24-hour recall method and analysed using a modified version of the Foodworks 210 Nutrient Calculation Software. Another group of healthy controls (n = 9) were supplemented with 20 mg/day lycopene for 4 weeks. Carotenoids (beta-carotene, lycopene, alpha-carotene, beta-cryptoxanthin, lutein/zeaxanthin) were measured by HPLC. RESULTS: Despite similar dietary intake, whole blood levels of total carotenoids, lycopene, lutein, beta-cryptoxanthin, alpha-carotene and beta-carotene were significantly lower in asthma than controls. However, there were no differences in plasma or sputum carotenoid levels. Induced sputum carotenoid levels were significantly lower than plasma and whole blood levels, but correlated strongly with plasma levels (r = 0.798, p < 0.001). Although there were no overall increases in either plasma or sputum lycopene levels following supplementation, changes in airway lycopene levels correlated with changes in plasma levels (r = 0.908, p < 0.002). CONCLUSIONS: Whole blood, but not plasma or sputum, carotenoid levels are deficient in asthma. Plasma carotenoid levels reflect airway carotenoid levels and when plasma levels are improved using oral supplements this is reflected in the airways.",
"title": "Airway and circulating levels of carotenoids in asthma and healthy controls."
},
{
"docid": "MED-3024",
"text": "This experiment aimed to study the molecular toxicity of methylmercury (MeHg) in liver, brain and white muscle of Atlantic salmon fed a diet based on fish oil (FO, high dietary n-3/n-6 ratio) compared to an alternative diet mainly based on vegetable oil (VO, low dietary n-3/n-6 ratio). Juvenile salmon were fed decontaminated diets or the FO and VO diets enriched with 5 mg Hg/kg (added as MeHg) for three months. The dietary lipid composition affected the fatty acid composition in the tissues, especially in liver and white muscle. After 84 days of exposure, the liver accumulated three times as much MeHg as the brain and white muscle. Vitamin C content and heme oxygenase, tubulin alpha (TUBA) and Cpt1 transcriptional levels all showed significant effects of MeHg exposure in the liver. TBARS, α-tocopherol, γ-tocopherol, and the transcriptional levels of thioredoxin, heme oxygenase, TUBA, PPARB1, D5D and D6D showed an effect of dietary lipid composition in liver tissue. Effects of dietary lipids were observed in brain tissue for MT-A, HIF1, Bcl-X and TUBA. Interaction effects between MeHg exposure and dietary lipid composition were observed in all tissues. Our data suggest that dietary fats have modulating effects on MeHg toxicity in Atlantic salmon. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Dietary lipids modulate methylmercury toxicity in Atlantic salmon."
},
{
"docid": "MED-2451",
"text": "BACKGROUND—A prospective cohort study of 2512 Welshmen aged 45-59 living in Caerphilly in 1979-1983 was used to investigate associations between diet and lung function. METHODS—At baseline (phase I) and at five year follow up (phase II), forced expiratory volume in one second (FEV1) was measured using a McDermott spirometer and dietary data were obtained using a semi-quantitative food frequency questionnaire. RESULTS—Good lung function, indicated by high maximum FEV1 given age and height, was associated with high intakes of vitamin C, vitamin E, β-carotene, citrus fruit, apples, and the frequent consumption of fruit juices/squashes. Lung function was inversely associated with magnesium intake but there was no evidence of an association with fatty fish. Following adjustment for confounders including body mass index, smoking history, social class, exercise, and total energy intake, only the associations with vitamin E and apples persisted, with lung function estimated to be 39 ml (95% confidence interval (CI) 9 to 69) higher for vitamin E intakes one standard deviation (SD) apart and 138 ml higher (95% CI 58to 218) for those eating five or more apples per week compared with non-consumers. Decline in lung function between phases was not significantly associated with the changing intakes of apples or vitamin E. An association between high average apple consumption and slow decline in lung function lost significance after adjustment for confounders. CONCLUSIONS—A strong positive association is seen between lung function and the number of apples eaten per week cross sectionally, consistent with a protective effect of hard fruit rather than soft/citrus fruit. The recent suggestion that such effects are reversible was not supported by our longitudinal analysis.",
"title": "Diet, lung function, and lung function decline in a cohort of 2512 middle aged men"
},
{
"docid": "MED-3029",
"text": "Background: Diverse perspectives have influenced fish consumption choices. Objectives: We summarized the issue of fish consumption choice from toxicological, nutritional, ecological, and economic points of view; identified areas of overlap and disagreement among these viewpoints; and reviewed effects of previous fish consumption advisories. Methods: We reviewed published scientific literature, public health guidelines, and advisories related to fish consumption, focusing on advisories targeted at U.S. populations. However, our conclusions apply to groups having similar fish consumption patterns. Discussion: There are many possible combinations of matters related to fish consumption, but few, if any, fish consumption patterns optimize all domains. Fish provides a rich source of protein and other nutrients, but because of contamination by methylmercury and other toxicants, higher fish intake often leads to greater toxicant exposure. Furthermore, stocks of wild fish are not adequate to meet the nutrient demands of the growing world population, and fish consumption choices also have a broad economic impact on the fishing industry. Most guidance does not account for ecological and economic impacts of different fish consumption choices. Conclusion: Despite the relative lack of information integrating the health, ecological, and economic impacts of different fish choices, clear and simple guidance is necessary to effect desired changes. Thus, more comprehensive advice can be developed to describe the multiple impacts of fish consumption. In addition, policy and fishery management inter-ventions will be necessary to ensure long-term availability of fish as an important source of human nutrition.",
"title": "Which Fish Should I Eat? Perspectives Influencing Fish Consumption Choices"
},
{
"docid": "MED-3033",
"text": "Rates of lung cancer in American men have greatly exceeded those in Japanese men for several decades despite the higher smoking prevalence in Japanese men. It is not known whether the relative risk of lung cancer associated with cigarette smoking is lower in Japanese men than American men and whether these risks vary by the amount and duration of smoking. To estimate smoking-specific relative risks for lung cancer in men, a multicentric case-control study was carried out in New York City, Washington, DC, and Nagoya, Japan from 1992 to 1998. A total of 371 cases and 373 age-matched controls were interviewed in United States hospitals and 410 cases and 252 hospital controls in Japanese hospitals; 411 Japanese age-matched healthy controls were also randomly selected from electoral rolls. The odds ratio (OR) for lung cancer in current United States smokers relative to nonsmokers was 40.4 [95% confidence interval (CI) = 21.8-79.6], which was >10 times higher than the OR of 3.5 for current smokers in Japanese relative to hospital controls (95% CI = 1.6-7.5) and six times higher than in Japanese relative to community controls (OR = 6.3; 95% CI = 3.7-10.9). There were no substantial differences in the mean number of years of smoking or average daily number of cigarettes smoked between United States and Japanese cases or between United States and Japanese controls, but American cases began smoking on average 2.5 years earlier than Japanese cases. The risk of lung cancer associated with cigarette smoking was substantially higher in United States than in Japanese males, consistent with population-based statistics on smoking prevalence and lung cancer incidence. Possible explanations for this difference in risk include a more toxic cigarette formulation of American manufactured cigarettes as evidenced by higher concentrations of tobacco-specific nitrosamines in both tobacco and mainstream smoke, the much wider use of activated charcoal in the filters of Japanese than in American cigarettes, as well as documented differences in genetic susceptibility and lifestyle factors other than smoking.",
"title": "Smoking and lung cancer risk in American and Japanese men: an international case-control study."
},
{
"docid": "MED-2471",
"text": "The International Study of Asthma and Allergies in Childhood (ISAAC) Phase One showed large worldwide variations in the prevalence of symptoms of asthma, rhinoconjunctivitis and eczema, up to 10 to 20 fold between countries. Ecological analyses were undertaken with ISAAC Phase One data to explore factors that may have contributed to these variations, and are summarised and reviewed here. In ISAAC Phase One the prevalence of symptoms in the past 12 months of asthma, rhinoconjunctivitis and eczema were estimated from studies in 463,801 children aged 13 - 14 years in 155 centres in 56 countries, and in 257,800 children aged 6-7 years in 91 centres in 38 countries. Ecological analyses were undertaken between symptom prevalence and the following: Gross National Product per capita (GNP), food intake, immunisation rates, tuberculosis notifications, climatic factors, tobacco consumption, pollen, antibiotic sales, paracetamol sales, and outdoor air pollution. Symptom prevalence of all three conditions was positively associated with GNP, trans fatty acids, paracetamol, and women smoking, and inversely associated with food of plant origin, pollen, immunisations, tuberculosis notifications, air pollution, and men smoking. The magnitude of these associations was small, but consistent in direction between conditions. There were mixed associations of climate and antibiotic sales with symptom prevalence. The potential causality of these associations warrant further investigation. Factors which prevent the development of these conditions, or where there is an absence of a positive correlation at a population level may be as important from the policy viewpoint as a focus on the positive risk factors. Interventions based on small associations may have the potential for a large public health benefit.",
"title": "Which population level environmental factors are associated with asthma, rhinoconjunctivitis and eczema? Review of the ecological analyses of ISAAC Phase One"
},
{
"docid": "MED-2484",
"text": "Paediatric asthma is a major clinical concern worldwide and represents a huge burden on family and society. It accounts for a large number of lost school days and may deprive the child of both academic achievement and social interaction. Childhood asthma also places strain on healthcare resources as a result of doctor and hospital visits and the cost of treatment. The prevalence of asthma varies worldwide, possibly because of different exposure to respiratory infection, indoor and outdoor pollution, and diet. Certain risk factors appear to predispose children to developing asthma and atopic disease, including incidence and severity of wheezing, atopy, maternal smoking, and number of fever episodes. This paper discusses the burden, prevalence, and risk factors associated with paediatric asthma.",
"title": "The burden of childhood asthma"
},
{
"docid": "MED-2645",
"text": "The development of the male reproductive ducts and external genitalia in vertebrates is dependent on elevated androgen concentrations during embryonic development and the period of postnatal growth. We have observed that a population of juvenile alligators living on Lake Apopka exhibit significantly smaller penis size (24% average decrease) and lower plasma concentrations of testosterone (70% lower concentrations) when compared to animals of similar size on Lake Woodruff. In addition to smaller phalli, no relationship exists between plasma testosterone concentrations and penile size in males from Lake Apopka, whereas a positive relationship exists for males from Lake Woodruff. The alligators on Lake Apopka are known to have elevated concentrations of the antiandrogenic DDT breakdown product p.p'-DDE stored in their fat. We suggest a number of hypotheses that could explain the modification in the phenotype of the juvenile male living in Lake Apopka. These modifications in phenotype include a smaller penis size, lower plasma androgen concentrations, and lack of responsiveness of the penis to the plasma androgens present.",
"title": "Reduction in penis size and plasma testosterone concentrations in juvenile alligators living in a contaminated environment."
},
{
"docid": "MED-2752",
"text": "CONTEXT: Considerable controversy exists regarding the association of omega-3 polyunsaturated fatty acids (PUFAs) and major cardiovascular end points. OBJECTIVE: To assess the role of omega-3 supplementation on major cardiovascular outcomes. DATA SOURCES: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials through August 2012. STUDY SELECTION: Randomized clinical trials evaluating the effect of omega-3 on all-cause mortality, cardiac death, sudden death, myocardial infarction, and stroke. DATA EXTRACTION: Descriptive and quantitative information was extracted; absolute and relative risk (RR) estimates were synthesized under a random-effects model. Heterogeneity was assessed using the Q statistic and I2. Subgroup analyses were performed for the presence of blinding, the prevention settings, and patients with implantable cardioverter-defibrillators, and meta-regression analyses were performed for the omega-3 dose. A statistical significance threshold of .0063 was assumed after adjustment for multiple comparisons. DATA SYNTHESIS: Of the 3635 citations retrieved, 20 studies of 68,680 patients were included, reporting 7044 deaths, 3993 cardiac deaths, 1150 sudden deaths, 1837 myocardial infarctions, and 1490 strokes. No statistically significant association was observed with all-cause mortality (RR, 0.96; 95% CI, 0.91 to 1.02; risk reduction [RD] -0.004, 95% CI, -0.01 to 0.02), cardiac death (RR, 0.91; 95% CI, 0.85 to 0.98; RD, -0.01; 95% CI, -0.02 to 0.00), sudden death (RR, 0.87; 95% CI, 0.75 to 1.01; RD, -0.003; 95% CI, -0.012 to 0.006), myocardial infarction (RR, 0.89; 95% CI, 0.76 to 1.04; RD, -0.002; 95% CI, -0.007 to 0.002), and stroke (RR, 1.05; 95% CI, 0.93 to 1.18; RD, 0.001; 95% CI, -0.002 to 0.004) when all supplement studies were considered. CONCLUSION: Overall, omega-3 PUFA supplementation was not associated with a lower risk of all-cause mortality, cardiac death, sudden death, myocardial infarction, or stroke based on relative and absolute measures of association.",
"title": "Association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events: a systematic review and meta-analysis."
},
{
"docid": "MED-2458",
"text": "BACKGROUND: Antioxidant-rich diets are associated with reduced asthma prevalence in epidemiologic studies. We previously showed that short-term manipulation of antioxidant defenses leads to changes in asthma outcomes. OBJECTIVE: The objective was to investigate the effects of a high-antioxidant diet compared with those of a low-antioxidant diet, with or without lycopene supplementation, in asthma. DESIGN: Asthmatic adults (n = 137) were randomly assigned to a high-antioxidant diet (5 servings of vegetables and 2 servings of fruit daily; n = 46) or a low-antioxidant diet (≤2 servings of vegetables and 1 serving of fruit daily; n = 91) for 14 d and then commenced a parallel, randomized, controlled supplementation trial. Subjects who consumed the high-antioxidant diet received placebo. Subjects who consumed the low-antioxidant diet received placebo or tomato extract (45 mg lycopene/d). The intervention continued until week 14 or until an exacerbation occurred. RESULTS: After 14 d, subjects consuming the low-antioxidant diet had a lower percentage predicted forced expiratory volume in 1 s and percentage predicted forced vital capacity than did those consuming the high-antioxidant diet. Subjects in the low-antioxidant diet group had increased plasma C-reactive protein at week 14. At the end of the trial, time to exacerbation was greater in the high-antioxidant than in the low-antioxidant diet group, and the low-antioxidant diet group was 2.26 (95% CI: 1.04, 4.91; P = 0.039) times as likely to exacerbate. Of the subjects in the low-antioxidant diet group, no difference in airway or systemic inflammation or clinical outcomes was observed between the groups that consumed the tomato extract and those who consumed placebo. CONCLUSIONS: Modifying the dietary intake of carotenoids alters clinical asthma outcomes. Improvements were evident only after increased fruit and vegetable intake, which suggests that whole-food interventions are most effective. This trial was registered at http://www.actr.org.au as ACTRN012606000286549.",
"title": "Manipulating antioxidant intake in asthma: a randomized controlled trial."
},
{
"docid": "MED-4551",
"text": "Interest has increased in the possibility that maternal dietary intake during pregnancy might influence the development of allergic disorders in children. The present prospective study examined the association of maternal intake of selected foods high in fatty acids and specific types of fatty acids during pregnancy with the risk of suspected atopic eczema among Japanese infants aged 3-4 months. Subjects were 771 mother-child pairs. Information on maternal dietary intake during pregnancy was assessed with a validated self-administered diet history questionnaire. The term 'suspected atopic eczema' was used to define an outcome based on results of our questionnaire completed by mothers 3-4 months postpartum. The risk of suspected atopic eczema was 8.4% (n = 65). Higher maternal intake of meat during pregnancy was significantly associated with an increased risk of suspected atopic eczema in the offspring: the multivariate odds ratio (OR) for the highest vs. lowest quartile was 2.59 [95% confidence interval (CI): 1.15-6.17, p for trend = 0.01]. The positive association was strengthened when the definition of the outcome was confined to a definite physician's diagnosis of atopic eczema (n = 35): the multivariate OR between extreme quartiles was 3.53 (95% CI: 1.19-12.23, p for trend = 0.02). No material exposure-response relationships were observed between maternal intake of eggs, dairy products, fish, total fat, saturated fatty acids, monounsaturated fatty acids, n-3 polyunsaturated fatty acids, alpha-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, n-6 polyunsaturated fatty acids, linoleic acid, arachidonic acid and cholesterol and the ratio of n-3 to n-6 polyunsaturated fatty acid consumption and the risk of suspected atopic eczema. Higher maternal meat intake may increase the risk of infantile atopic eczema, whereas we found no evidence that maternal intake of fish and n-3 polyunsaturated fatty acids are preventive against infantile atopic eczema. (c) 2009 John Wiley & Sons A/S",
"title": "Maternal meat and fat consumption during pregnancy and suspected atopic eczema in Japanese infants aged 3-4 months: the Osaka Maternal and Child He..."
}
] |
[
{
"docid": "MED-4943",
"text": "Fish and seal oil dietary supplements, marketed to be rich in omega-3 fatty acids, are frequently consumed by Canadians. Samples of these supplements (n = 30) were collected in Vancouver, Canada, between 2005 and 2007. All oil supplements were analyzed for polychlorinated biphenyls (PCBs) and organochlorine insecticides (OCs) and each sample was found to contain detectable residues. The highest SigmaPCB and SigmaDDT (1,1,1-trichloro-di-(4-chlorophenyl)ethane) concentrations (10400 ng/g and 3310 ng/g, respectively) were found in a shark oil sample while lowest levels were found in supplements prepared using mixed fish oils (anchovy, mackerel, and sardine) (0.711 ng SigmaPCB/g and 0.189 ng SigmaDDT/g). Mean SigmaPCB concentrations in oil supplements were 34.5, 24.2, 25.1, 95.3, 12.0, 5260, 321, and 519 ng/g in unidentified fish, mixed fish containing no salmon, mixed fish with salmon, salmon, vegetable with mixed fish, shark, menhaden (n = 1), and seal (n = 1), respectively. Maximum concentrations of the other OCs were generally observed in the seal oil. The hexachlorinated PCB congeners were the dominant contributors to SigmaPCB levels, while SigmaDDT was the greatest contributor to organochlorine levels. Intake estimates were made using maximum dosages on manufacturers' labels and results varied widely due to the large difference in residue concentrations obtained. Average SigmaPCB and SigmaDDT intakes were calculated to be 736 +/- 2840 ng/d and 304 +/- 948 ng/d, respectively.",
"title": "Persistent organic pollutants in fish oil supplements on the Canadian market: polychlorinated biphenyls and organochlorine insecticides."
},
{
"docid": "MED-4730",
"text": "We successfully optimized an analytical method using gel permeation chromatography followed by direct sample introduction comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry to quantify multiple groups of targeted persistent organic pollutants and halogenated natural products (HNPs) simultaneously in fish oil samples. This new method has a wider analytical scope than the traditional approach to use multiple methods to cover each class of compounds. Our analysis revealed that the relatively more volatile and lighter organic compounds, such as polychlorinated biphenyls (PCBs), organochlorine pesticides, and other smaller organohalogen compounds, were still present in two brands of \"PCB-free\" cod liver oils, albeit at much lower levels than in an untreated commercial sample. Moreover, the less volatile organic compounds, such as polybrominated diphenyl ethers and brominated HNPs, were detected at similar levels in all three cod liver oils. This suggests that the commercial molecular distillation treatment used for removal of organic/inorganic toxic contaminants is only effective for the lighter organic contaminants.",
"title": "Simultaneous quantitation of multiple classes of organohalogen compounds in fish oils with direct sample introduction comprehensive two-dimensional..."
},
{
"docid": "MED-4731",
"text": "BACKGROUND: A high intake of n-3 polyunsaturated fatty acids (PUFAs), mainly present in fish, may be associated with decreased inflammation. Previous intervention studies on fish PUFA and inflammatory markers in healthy individuals did not analyze a broad spectrum of inflammatory cytokines, chemokines and cell adhesion molecules, or their interrelationships. Therefore, we determined the effects of fish oil supplementation on 19 serum inflammatory markers and their interrelationships in healthy, middle-aged individuals. METHODS: Individuals (n=77) aged 50-70 years completed a randomized, double-blind placebo-controlled intervention study. Participants received 3.5 g/day fish oil (1.5 g/day total n-3 PUFA) (n=39) or placebo (high oleic sunflower oil) (n=38) for 12 weeks. Serum concentrations of 19 inflammatory markers were determined using a multiplex immunoassay before and after intervention. Changes in concentrations were analyzed using analysis of covariance and differences in patterns in inflammatory markers between the fish oil and placebo group were analyzed by principal component analysis. RESULTS: Fish oil supplementation did not significantly affect serum concentrations of cytokines, chemokines or cell adhesion molecules as compared with placebo. However, there was a trend for all inflammatory markers to increase after fish oil supplementation. PCA did not result in markedly distinctive patterns of inflammatory markers for the fish oil and placebo group. CONCLUSION: In conclusion, this 12-week randomized, double-blind placebo-controlled intervention trial did not show that 1.5 g/day n-3 PUFA significantly affected the serum inflammatory response in healthy individuals, nor did patterns of inflammatory markers. Thus, a healthy middle-aged population may not benefit from fish oil as an anti-inflammatory agent.",
"title": "No effect of fish oil supplementation on serum inflammatory markers and their interrelationships: a randomized controlled trial in healthy, middle-..."
},
{
"docid": "MED-2412",
"text": "OBJECTIVE: To determine the effects of fish oil supplementation on lipid levels and glycemic control in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A comprehensive search of Medline, Embase, Lilacs, the Cochrane Clinical Trials Registry bibliographies of relevant papers, and expert input updated through September 1998 was undertaken. All randomized placebo-controlled trials were included in which fish oil supplementation was the only intervention in subjects with type 2 diabetes. Three investigators performed data extraction and quality scoring independently with discrepancies resolved by consensus. Eighteen trials including 823 subjects followed for a mean of 12 weeks were included. Doses of fish oil used ranged from 3 to 18 g/day The outcomes studied were glycemic control and lipid levels. RESULTS: Meta-analysis of pooled data demonstrated a statistically significant effect of fish oil on lowering triglycerides (-0.56 mmol/l [95% CI -0.71 to -0.41]) and raising LDL cholesterol (0.21 mmol/l [0.02 to 0.41]). No statistically significant effect was observed for fasting glucose. HbA1c total cholesterol, or HDL cholesterol. The triglyceride-lowering effect and the elevation in LDL cholesterol were most marked in those trials that recruited hypertriglyceridemic subjects and used higher doses of fish oil. Heterogeneity was observed and explained by the recruitment of subjects with baseline hypertriglyceridemia in some studies. CONCLUSIONS: Fish oil supplementation in type 2 diabetes lowers triglycerides, raises LDL cholesterol, and has no statistically significant effect on glycemic control. Trials with hard clinical end points are needed.",
"title": "Fish oil supplementation in type 2 diabetes: a quantitative systematic review."
},
{
"docid": "MED-839",
"text": "Long-chain EPA/DHA omega-3 fatty acid supplementation can be co-preventative and co-therapeutic. Current research suggests increasing accumulated long chain omega-3s for health benefits and as natural medicine in several major diseases. But many believe plant omega-3 sources are nutritionally and therapeutically equivalent to the EPA/DHA omega-3 in fish oil. Although healthy, precursor ALA bio-conversion to EPA is inefficient and production of DHA is nearly absent, limiting the protective value of ALA supplementation from flax-oil, for example. Along with pollutants certain fish acquire high levels of EPA/DHA as predatory species. However, the origin of EPA/DHA in aquatic ecosystems is algae. Certain microalgae produce high levels of EPA or DHA. Now, organically produced DHA-rich microalgae oil is available. Clinical trials with DHA-rich oil indicate comparable efficacies to fish oil for protection from cardiovascular risk factors by lowering plasma triglycerides and oxidative stress. This review discusses 1) omega-3 fatty acids in nutrition and medicine; 2) omega-3s in physiology and gene regulation; 3) possible protective mechanisms of EPA/DHA in major diseases such as coronary heart disease, atherosclerosis, cancer and type 2 diabetes; 4) EPA and DHA requirements considering fish oil safety; and 5) microalgae EPA and DHA-rich oils and recent clinical results.",
"title": "Omega-3 fatty acids for nutrition and medicine: considering microalgae oil as a vegetarian source of EPA and DHA."
},
{
"docid": "MED-4114",
"text": "Induced apoptosis of autoreactive T-lymphocyte precursors in the thymus is crucial for the prevention of autoimmune disorders. IGF-I and prolactin, which are lymphocyte growth factors, may have the potential to suppress apoptosis in thymocytes and thus encourage autoimmunity; conversely, dietary fish oil rich in omega-3 fats appears to upregulate apoptosis in lymphocytes. Since whole-food vegan diets may downregulate systemic IGF-I activity, it is proposed that such a diet, in conjunction with fish oil supplementation and treatment with dopamine agonists capable of suppressing prolactin secretion, may have utility for treating and preventing autoimmune disorders. This prediction is consistent with the extreme rarity of autoimmune disorders among sub-Saharan black Africans as long as they followed their traditional quasi-vegan lifestyles, and with recent ecologic studies correlating risks for IDDM and for multiple sclerosis mortality with animal product and/or saturated fat consumption. Moreover, there is evidence that vegan or quasi-vegan diets are useful in the management of rheumatoid arthritis, multiple sclerosis, and possibly SLE. The dopamine agonist bromocryptine exerts anti-inflammatory effects in rodent models of autoimmunity, and there is preliminary evidence that this drug may be clinically useful in several human autoimmune diseases; better tolerated D2-specific agonists such as cabergoline may prove to be more practical for use in therapy. The moderate clinical utility of supplemental fish oil in rheumatoid arthritis and certain other autoimmune disorders is documented. It is not unlikely that extra-thymic anti-inflammatory effects contribute importantly to the clinical utility of vegan diets, bromocryptine, and fish oil in autoimmunity. The favorable impact of low latitude or high altitude on autoimmune risk may be mediated by superior vitamin D status, which is associated with decreased secretion of parathyroid hormone; there are theoretical grounds for suspecting that parathyroid hormone may inhibit apoptosis in thymocytes. Androgens appear to up-regulate thymocyte apoptosis, may be largely responsible for the relative protection from autoimmunity enjoyed by men, and merit further evaluation for the management of autoimmunity in women. It will probably prove more practical to prevent autoimmune disorders than to reverse them once established; a whole-food vegan diet, coupled with fish oil and vitamin D supplementation, may represent a practical strategy for achieving this prevention, while concurrently lowering risk for many other life-threatening 'Western' diseases. Copyright 2001 Harcourt Publishers Ltd.",
"title": "Upregulation of lymphocyte apoptosis as a strategy for preventing and treating autoimmune disorders: a role for whole-food vegan diets, fish oil an..."
},
{
"docid": "MED-5100",
"text": "Historically, concerns with fish consumption have addressed risks from contaminants (e.g., methylmercury (MeHg), and PCBs). More recently public health concerns have widened in appreciation of the specific benefits of fish consumption such as those arising from polyunsaturated fatty acids (PUFAs) in fish oil. Fish contains varying levels of PUFAs and MeHg. Since both address the same health outcomes (in opposite directions) and occur together in fish, great care must be exercised in providing public health guidance. Mozaffarian and Rimm in a recent article (JAMA. 2006, 296:1885–99) have made a strong case for the beneficial effects of PUFAs in reducing the risk of coronary heart disease, but at the same time, have also broadly discounted the increased risks of coronary heart disease posed by MeHg in fish, stating that \"... among adults... the benefits of fish intake exceed the potential risks.\" This conclusion appears to be based on an inaccurate and insufficiently critical analysis of the literature. This literature is re-examined in light of their conclusions, and the available and appropriate public health options are considered.",
"title": "Public health guidance on cardiovascular benefits and risks related to fish consumption"
},
{
"docid": "MED-4631",
"text": "BACKGROUND: Patients with rheumatoid arthritis (RA) improve on a vegetarian diet or supplementation with fish oil. We investigated the effects of both dietary measures, alone and in combination, on inflammation, fatty acid composition of erythrocyte lipids, eicosanoids, and cytokine biosynthesis in patients with RA. METHODS: Sixty-eight patients with definitive RA were matched into two groups of 34 subjects each. One group was observed for 8 months on a normal western diet (WD) and the other on an anti-inflammatory diet (AID) providing an arachidonic acid intake of less than 90 mg/day. Patients in both groups were allocated to receive placebo or fish oil capsules (30 mg/kg body weight) for 3 months in a double-blind crossover study with a 2-month washout period between treatments. Clinical examination and routine laboratory findings were evaluated every month, and erythrocyte fatty acids, eicosanoids, and cytokines were evaluated before and after each 3-month experimental period. RESULTS: Sixty patients completed the study. In AID patients, but not in WD patients, the numbers of tender and swollen joints decreased by 14% during placebo treatment. In AID patients, as compared to WD patients, fish oil led to a significant reduction in the numbers of tender (28% vs 11%) and swollen (34% vs 22%) joints (P<0.01). Compared to baseline levels, higher enrichment of eicosapentaenoic acid in erythrocyte lipids (244% vs 217%) and lower formation of leukotriene B(4) (34% vs 8%, P>0.01), 11-dehydro-thromboxane B(2) (15% vs 10%, P<0.05), and prostaglandin metabolites (21% vs 16%, P<0.003) were found in AID patients, especially when fish oil was given during months 6-8 of the experiment. CONCLUSION: A diet low in arachidonic acid ameliorates clinical signs of inflammation in patients with RA and augments the beneficial effect of fish oil supplementation.",
"title": "Anti-inflammatory effects of a low arachidonic acid diet and fish oil in patients with rheumatoid arthritis."
},
{
"docid": "MED-2391",
"text": "Objectives The objective of this article is to extend our previous studies of persistent organic pollutant (POP) contamination of U.S. food by measuring perfluorinated compounds (PFCs), organochlorine pesticides, and polychlorinated biphenyls (PCBs) in composite food samples. This study is part of a larger study reported in two articles, the other of which reports levels of polybrominated diphenyl ethers and hexabromocyclododecane brominated flame retardants in these composite foods [Schecter et al. 2010. Polybrominated diphenyl ethers (PBDEs) and hexabromocyclodecane (HBCD) in composite U.S. food samples, Environ Health Perspect 118:357–362]. Methods In this study we measured concentrations of 32 organochlorine pesticides, 7 PCBs, and 11 PFCs in composite samples of 31 different types of food (310 individual food samples) purchased from supermarkets in Dallas, Texas (USA), in 2009. Dietary intake of these chemicals was calculated for an average American. Results Contamination varied greatly among chemical and food types. The highest level of pesticide contamination was from the dichlorodiphenyltrichloroethane (DDT) metabolite p,p′- dichlorodiphenyldichloroethylene, which ranged from 0.028 ng/g wet weight (ww) in whole milk yogurt to 2.3 ng/g ww in catfish fillets. We found PCB congeners (28, 52, 101, 118, 138, 153, and 180) primarily in fish, with highest levels in salmon (PCB-153, 1.2 ng/g ww; PCB-138, 0.93 ng/g ww). For PFCs, we detected perfluorooctanoic acid (PFOA) in 17 of 31 samples, ranging from 0.07 ng/g in potatoes to 1.80 ng/g in olive oil. In terms of dietary intake, DDT and DDT metabolites, endosulfans, aldrin, PCBs, and PFOA were consumed at the highest levels. Conclusion Despite product bans, we found POPs in U.S. food, and mixtures of these chemicals are consumed by the American public at varying levels. This suggests the need to expand testing of food for chemical contaminants.",
"title": "Perfluorinated Compounds, Polychlorinated Biphenyls, and Organochlorine Pesticide Contamination in Composite Food Samples from Dallas, Texas, USA"
},
{
"docid": "MED-928",
"text": "Background Bioavailability of omega-3 fatty acids (FA) depends on their chemical form. Superior bioavailability has been suggested for phospholipid (PL) bound omega-3 FA in krill oil, but identical doses of different chemical forms have not been compared. Methods In a double-blinded crossover trial, we compared the uptake of three EPA+DHA formulations derived from fish oil (re-esterified triacylglycerides [rTAG], ethyl-esters [EE]) and krill oil (mainly PL). Changes of the FA compositions in plasma PL were used as a proxy for bioavailability. Twelve healthy young men (mean age 31 y) were randomized to 1680 mg EPA+DHA given either as rTAG, EE or krill oil. FA levels in plasma PL were analyzed pre-dose and 2, 4, 6, 8, 24, 48, and 72 h after capsule ingestion. Additionally, the proportion of free EPA and DHA in the applied supplements was analyzed. Results The highest incorporation of EPA+DHA into plasma PL was provoked by krill oil (mean AUC0-72 h: 80.03 ± 34.71%*h), followed by fish oil rTAG (mean AUC0-72 h: 59.78 ± 36.75%*h) and EE (mean AUC0-72 h: 47.53 ± 38.42%*h). Due to high standard deviation values, there were no significant differences for DHA and the sum of EPA+DHA levels between the three treatments. However, a trend (p = 0.057) was observed for the differences in EPA bioavailability. Statistical pair-wise group comparison's revealed a trend (p = 0.086) between rTAG and krill oil. FA analysis of the supplements showed that the krill oil sample contained 22% of the total EPA amount as free EPA and 21% of the total DHA amount as free DHA, while the two fish oil samples did not contain any free FA. Conclusion Further studies with a larger sample size carried out over a longer period are needed to substantiate our findings and to determine differences in EPA+DHA bioavailability between three common chemical forms of LC n-3 FA (rTAG, EE and krill oil). The unexpected high content of free EPA and DHA in krill oil, which might have a significant influence on the availability of EPA+DHA from krill oil, should be investigated in more depth and taken into consideration in future trials.",
"title": "Incorporation of EPA and DHA into plasma phospholipids in response to different omega-3 fatty acid formulations - a comparative bioavailability study of fish oil vs. krill oil"
},
{
"docid": "MED-5105",
"text": "Food, especially dairy products, meat, and fish, is the primary source of environmental exposure to dioxins in the general population. Little data exists on dioxin levels in the popular and widely consumed \"fast foods\". Data presented in a previously published pilot study was limited to measuring only the levels of dioxins and dibenzofurans in three types of U.S. fast food. This study adds to the previous paper by presenting data, in addition to dioxins and dibenzofurans, on the closely related dioxin-like polychlorinated biphenyls (PCBs), and the persistent metabolite of DDT, 1,1-dichloro-2,2-bis (p-chlorophenyl) ethylene (DDE), in four types of popular U.S. fast food. These include McDonald's Big Mac Hamburger, Pizza Hut's Personal Pan Pizza Supreme, Kentucky Fried Chicken (KFC) three piece original recipe mixed dark and white meat luncheon package, and Häagen-Daz chocolate-chocolate chip ice cream. Dioxin plus dibenzofuran dioxin toxic equivalents (TEQ) ranged from 0.03 to 0.28 TEQ pg/g wet or whole weight for the Big Mac, from 0.03 to 0.29 for the Pizza, from 0.01 to 0.31 for the KFC, and from 0.03 to 0.49 TEQ pg/g for the ice cream. Daily TEQ consumption per kilogram body weight (kg/BW), assuming an average 65 kg adult and a 20 kg child, from one serving of each of these fast food ranged between 0.046 and 1.556 pg/kg in adults whereas in children the values were between 0.15 and 5.05 pg/kg. Total measured PCDD/Fs in the Big Mac, Personal Pan Pizza, KFC, and the Häagen-Daz ice cream varied from 0.58 to 9.31 pg/g. Measured DDE levels in the fast foods ranged from 180 to 3170 pg/g. Total mono-ortho PCB levels ranged up to 500 pg/g or 1.28 TEQ pg/g for the KFC and for di-ortho PCBs up to 740 pg/g or 0.014 TEQ pg/g for the pizza sample. Total PCB values in the four samples ranged up to 1170 pg/g or 1.29 TEQ pg/g for the chicken sample.",
"title": "Dioxins, dibenzofurans, dioxin-like PCBs, and DDE in U.S. fast food, 1995."
},
{
"docid": "MED-1098",
"text": "The first U.S. nationwide food sampling with measurement of dioxins, dibenzofurans, and coplanar, mono-ortho and di-ortho polychlorinated biphenyls (PCBs) is reported in this study. Twelve separate analyses were conducted on 110 food samples divided into pooled lots by category. The samples were purchased in 1995 in supermarkets in Atlanta, GA, Binghamton, NY, Chicago, IL, Louisville, KY, and San Diego, CA. Human milk also was collected to estimate nursing infants' consumption. The food category with highest World Health Organization (WHO) dioxin toxic equivalent (TEQ) concentration was farm-grown freshwater fish fillet with 1.7 pg/g, or parts per trillion (ppt), wet, or whole, weight. The category with the lowest TEQ level was a simulated vegandiet, with 0.09 ppt. TEQ concentrations in ocean fish, beef, chicken, pork, sandwich meat, eggs, cheese, and ice cream, as well as human milk, were in the range O.33 to 0.51 ppt, wet weight. In whole dairy milk TEQ was 0.16 ppt, and in butter 1.1 ppt. Mean daily intake of TEQ for U.S. breast-fed infants during the first year of life was estimated at 42 pg/kg body weight. For children aged 1-11 yr the estimated daily TEQ intake was 6.2 pg/kg body weight. For males and females aged 12-19 yr, the estimated TEQ intake was 3.5 and 2.7 pg/kg body weight, respectively. For adult men and women aged 20-79 yr, estimated mean daily TEQ intakes were 2.4 and 2.2 pg/kg body weight, respectively. Estimated mean daily intake of TEQ declined with age to a low of 1.9 pg/kg body weight at age 80 yr and older. For all ages except 80 yr and over, estimates were higher for males than females. For adults, dioxins, dibenzofurans, and PCBs contributed 42%, 30%, and 28% of dietary TEQ intake, respectively. DDE was also analyzed in the pooled food samples.",
"title": "Intake of dioxins and related compounds from food in the U.S. population."
},
{
"docid": "MED-2397",
"text": "Background Studies have demonstrated ubiquitous human exposure to persistent organic pollutants (POPs) such as p,p′-diphenyldichloroethene (DDE) and polychlorinated biphenyls (PCBs). Although there is considerable evidence that POP exposures are associated with prevalent diabetes, these studies do not establish causality because the cross-sectional study design does not allow for assessment of temporality of the exposure–disease association. Prospective studies, however, have been lacking. Objectives This study was designed to determine whether POP body burdens are related to incidence of diabetes in a cohort of Great Lakes sport fish consumers. Methods The cohort was established in the early 1990s and followed through 2005. We tested serum for DDE and PCB congeners and assessed diabetes diagnosis, demographics, and fish consumption. Associations of diabetes with exposures were examined prospectively in participants without diabetes in 1994–1995, followed through 2005. Annual percent changes in DDE and PCB-132/153 from 1994 to 2005 were examined by diabetes status. Results DDE exposure was associated with incident diabetes. Incident diabetes was not associated with mono-ortho PCB-118, total PCBs, or years of sport fish consumption. Annual percent change in DDE and PCB-132/153 did not differ significantly by diabetes status. Conclusions This study demonstrates an association between DDE exposure and incident diabetes. The findings of an association of DDE with incident diabetes and the lack of effect of diabetes on annual percent change in POPs do not support the hypothesis that associations of POPs with diabetes are attributable to reverse causality. Additional studies should address the biological pathways by which DDE could affect glucose homeostasis.",
"title": "Organochlorine Exposure and Incidence of Diabetes in a Cohort of Great Lakes Sport Fish Consumers"
},
{
"docid": "MED-4180",
"text": "The aim was to determine half-life of six most abundant PCB congeners in the body of early adolescents. In 304 environmentally exposed children, PCB serum concentration was determined at the age of 8 and 12years. Half-life was determined for each child assuming exponential decrease or for the whole cohort using multiple regression. Results obtained by both approaches were in agreement. PCB reuptakes corrupting half-life estimates for each child and each congener were evaluated. If one of the serum PCB concentration values fell below the level of detection (LOD) the pair was excluded and if PCB half-life value exceeded the arbitrary value of 30years. The following median half-lives in years 4.46, 10.59, 9.7, 4.7, 9.1 and 9.8 were obtained for PCB congeners 118, 138(+163), 153, 156(+171), 170 and 180, respectively. The elimination half-life values were not systematically related to PCB serum concentration at any examination age. Between half-life values, percentage of children with significant reuptakes and PCB congener abundance in serum were found significant associations. Copyright © 2010 Elsevier Ltd. All rights reserved.",
"title": "Half-lives of serum PCB congener concentrations in environmentally exposed early adolescents."
},
{
"docid": "MED-2496",
"text": "Persistent organic pollutants (POPs) exert harmful effects on cognitive, endocrine and immune functions and bioaccumulate in the environment and human tissues. The aim of this study was to investigate the body burden of several POPs in the adult population (n=246) and their association to diet and other lifestyle factors in a Swedish national survey. Serum concentrations of several polychlorinated biphenyls (PCBs), and the pesticides hexachlorobenzene (HCB), β-hexachlorocyclohexane (β-HCH), chlordane compounds and dichlorodiphenyldichloroethylene (DDE) were determined by liquid-liquid extraction, silica column cleanup and gas chromatography high resolution mass spectrometry. Diet was assessed using 4-day food records and complementary dietary and lifestyle factors by questionnaire. Fish intake was additionally assessed by plasma fatty acid composition. Clustering of the compounds revealed that PCBs were separated into two clusters, one including low-chlorinated PCB 28 and 52, and the other high-chlorinated mono- and di-ortho PCBs, suggesting similarities and dissimilarities in exposure sources and possibly also toxicokinetics. Men had 24% and 32% higher levels of PCB 138-180 and chlordane compounds, respectively, compared with women. This may partly be explained by elimination of the POPs among women reporting a history of breastfeeding. The proportion of very long-chain n-3 fatty acids in plasma were positively correlated with the pollutants: r=0.24 (PCB 28), r=0.33 (PCB 118), r=0.35 (PCB 138-180), r=0.29 (HCB), r=0.18 (β-HCH), r=0.34 (chlordane compounds), r=0.34 (p,p'-DDE), p≤0.005. Individuals consuming fatty Baltic fish≥1 time per months had 45% higher serum levels of PCB 118 compared with non-consumers. Levels of PCB 28 were associated with the age of the residential building. To conclude, the population-distributed approach of surveying dietary habits, lifestyle factors and POP body burdens, made it possible to identify personal characteristics associated with the POP body burdens in Sweden. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Fish intake and breastfeeding time are associated with serum concentrations of organochlorines in a Swedish population."
},
{
"docid": "MED-4170",
"text": "Researchers have long debated the adverse effects of exposure to polychlorinated biphenyls (PCBs) on children versus the benefits of breastfeeding. In this article, the authors provide an overview of the known health effects of PCBs in children and examine the level of evidence regarding the risk of postnatal exposure via breastfeeding. The major source of PCBs is environmental, with over 90% of human exposure through the food chain. PCB exposure in infants is predominantly via breast milk, but limited evidence exists of significant toxicity associated with this mode of transmission. Breastfeeding should, therefore, continue to be encouraged on the basis of evidence of the benefits derived from human milk coupled with inconclusive proof that lactational PCB exposure has major detrimental effects on the overall health and development of infants.",
"title": "To breastfeed or not to breastfeed: a review of the impact of lactational exposure to polychlorinated biphenyls (PCBs) on infants."
},
{
"docid": "MED-4936",
"text": "Food and nutrition professionals question whether supplement-sourced nutrients appear to be equivalent to those derived from natural food sources. We compared the nutritional availability of docosahexaenoic acid (DHA) from algal-oil capsules to that from assayed cooked salmon in 32 healthy men and women, ages 20 to 65 years, in a randomized, open-label, parallel-group study. In this 2-week study comparing 600 mg DHA/day from algal-oil capsules to that from assayed portions of cooked salmon, mean change from baseline in plasma phospholipids and erythrocyte DHA levels was analyzed and DHA levels were compared by Student's t tests. In post-hoc analyses to determine bioequivalence, least-squares mean ratios of percent change from baseline in plasma phospholipid and erythrocyte DHA levels were compared. DHA levels increased by approximately 80% in plasma phospholipids and by approximately 25% in erythrocytes in both groups. Changes in DHA levels in plasma phospholipids and erythrocytes were similar between groups. As measured by delivery of DHA to both plasma and erythrocytes, fish and algal-oil capsules were equivalent. Both regimens were generally well-tolerated. These results indicate that algal-oil DHA capsules and cooked salmon appear to be bioequivalent in providing DHA to plasma and red blood cells and, accordingly, that algal-oil DHA capsules represent a safe and convenient source of non-fish-derived DHA.",
"title": "Algal-oil capsules and cooked salmon: nutritionally equivalent sources of docosahexaenoic acid."
},
{
"docid": "MED-4934",
"text": "Concentrations of polybrominated diphenyl ethers (PBDEs), pesticides, polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons were measured in 136 fish from 14 remote lakes in 8 western US National Parks/Preserves between 2003 and 2005 and compared to human and wildlife contaminant health thresholds. A sensitive (median detection limit −18 pg/g wet weight), efficient (61% recovery at 8 ng/g), reproducible (4.1 %RSD), and accurate (7 % deviation from SRM) analytical method was developed and validated for these analyses. Concentrations of PCBs, hexachlorobenzene, hexachlorocyclohexanes, DDTs and chlordanes in western US fish were comparable to or lower than mountain fish recently collected from Europe, Canada, and Asia. Dieldrin and PBDE concentrations were higher than recent measurements in mountain fish and Pacific Ocean salmon. Concentrations of most contaminants in western US fish were 1–6 orders of magnitude below calculated recreational fishing contaminant health thresholds. However, contaminant concentrations exceeded subsistence fishing cancer screening values in 8 of 14 lakes. Average contaminant concentrations in fish exceeded wildlife contaminant health thresholds for piscivorous mammals in 5 lakes, and piscivorous birds in all 14 lakes. These results indicate that atmospherically deposited organic contaminants can accumulate in high elevation fish, reaching concentrations relevant to human and wildlife health.",
"title": "Atmospherically Deposited PBDEs, Pesticides, PCBs, and PAHs in Western US National Park Fish: Concentrations and Consumption Guidelines"
},
{
"docid": "MED-2917",
"text": "The effect of alternative dietary habits and prolonged lactation on the nutrient and contaminant concentrations in human milk was studied. The study sample consisted of mothers on macrobiotic diets, containing little or no diary products and meat, at 2-3 months postpartum (n = 9) and 9-13 months postpartum (n = 12), and mothers on omnivorous diets at 2-3 months postpartum (n = 10). Protein and zinc concentrations in breast-milk from macrobiotic mothers decreased with stage of lactation. After adjustment for stage of lactation, milk from macrobiotic mothers contained less calcium, magnesium and saturated fatty acids C15:0-C20:0, and more polyunsaturated fatty acids. Observed tendencies for lower protein and fat and higher lactose concentrations in the macrobiotic group were not statistically significant. Concentrations of vitamin B12, HCB and polychlorinated biphenyls (PCB 118, PCB 138, PCB 153 and PCB 180) were lower in the macrobiotic group. After adjustment for confounding variables, meat and fish consumption, but not dairy products, contributed to vitamin B12 concentrations. Meat and diary products strongly contributed to breast-milk concentrations of dieldrin and PCBs, fish to PCB 118, and smoking to DDT and dieldrin. Our findings suggest that breast-milk contamination could be reduced by abstinence from smoking and a moderate intake of animal products. However, risk of nutritional deficiencies rules out complete avoidance of meat, fish or diary products. Quantitative research on the effects of a reduced consumption of animal products, as well as smoking, on breast-milk contamination is warranted.",
"title": "Nutrients and contaminants in human milk from mothers on macrobiotic and omnivorous diets."
},
{
"docid": "MED-1171",
"text": "A number of chemicals have been shown to demonstrate neurotoxic effects either in human or laboratory animal studies. This article aims at evaluating the impact of exposure to several chemicals including: organophosphate, organochlorine pesticides, polychlorinated biphenyls (PCBs), mercury and lead on the neurodevelopment of children by reviewing the most recent published literature, and answer the question whether any progress has been made in the epidemiology of the neurodevelopment of children induced by exposure to those chemicals. The result of the presented studies show that exposure to the above-mentioned chemicals may impair the neurodevelopment of children. Neonates exposed to organophosphate pesticides demonstrated a higher proportion of abnormal reflexes, and young children had more attention problems. Exposure to organochlorine pesticides in children was associated with alertness, quality of alert responsiveness, cost of attention and other potential attention associated measures. The majority of studies indicate the negative impact of lead exposure at the level <10 µg/dl or even <5 µg/dl on the neurodevelopment of children. The results of studies on exposure to PCBs, mercury, and their effect on neurodevelopment are inconsistent. Some suggest that prenatal exposure to PCBs and mercury is related to performance impairments, attention and concentration problems, while other do not present any statistically significant association. The studies were mostly well designed, using prospective cohorts with the exposure assessment based on the biomarker of exposure. Concerning the covariates and confounders affecting the endpoints in most of the presented studies, confounders were included in data analysis. In order to recognize the early cognitive, motor and language outcomes of chemical exposures, well standardized tools were used for evaluating the neurodevelopmental effects and offer an early and fairly comprehensive measure of child development. Because the neurotoxicants may cross the placenta and the fetal brain, exposure consideration regarding the reduction of exposure to those chemicals should be implemented.",
"title": "Chemical exposure early in life and the neurodevelopment of children--an overview of current epidemiological evidence."
},
{
"docid": "MED-4735",
"text": "BACKGROUND/OBJECTIVES: To assess biomarkers and frequency questions as measures of fish consumption. SUBJECTS/METHODS: Participants in the Fishermen substudy numbered 125 men and 139 women (aged 22-74), and in the Health 2000 substudy, 577 men and 712 women (aged 45-74) participated. The aim of the Fishermen study was to examine the overall health effect of fish consumption in a high-consumption population, whereas the aim of the Health 2000 substudy was to obtain in-depth information on cardiovascular diseases and diabetes. Fish consumption was measured by the same validated food frequency questionnaire (FFQ) in both the studies, with a further two separate frequency questions used in the Fishermen substudy. Dioxins, polychlorinated biphenyls (PCBs) and methyl mercury (MeHg) (in the Fishermen substudy alone), and omega-3 polyunsaturated fatty acids (omega-3 PUFAs) (in both studies) were analyzed from fasting serum/blood samples. RESULTS: The Spearman's correlation coefficients between FFQ fish consumption and dioxins, PCBs, MeHg and omega-3 PUFAs were respectively 0.46, 0.48, 0.43 and 0.38 among the Fishermen substudy men, and 0.28, 0.36, 0.45 and 0.31 among women. Similar correlation coefficients were observed between FFQ fish consumption and serum omega-3 PUFAs in the Health 2000 substudy, and also between FFQ fish consumption and the frequency questions on fish consumption in the Fishermen substudy. According to multiple regression modeling and LMG metrics, the most important fish consumption biomarkers were dioxins and PCBs among the men and MeHg among the women. CONCLUSIONS: Environmental contaminants seemed to be slightly better fish consumption biomarkers than omega-3 PUFAs in the Baltic Sea area. The separate frequency questions measured fish consumption equally well when compared with the FFQ.",
"title": "Dioxins, polychlorinated biphenyls, methyl mercury and omega-3 polyunsaturated fatty acids as biomarkers of fish consumption."
},
{
"docid": "MED-3554",
"text": "A great deal of effort is now being devoted to the development of new drugs that hopefully will control the spread of inoperable cancer by safely inhibiting tumor-evoked angiogenesis. However, there is growing evidence that certain practical nutritional measures have the potential to slow tumor angiogenesis, and it is reasonable to anticipate that, by combining several measures that work in distinct but complementary ways to impede the angiogenic process, a clinically useful 'multifocal angiostatic therapy' (MAT) might be devised. Several measures which might reasonably be included in such a protocol are discussed below, and include: a low-fat, low-glycemic index vegan diet, which may down-regulate the systemic IGF-I activity that supports angiogenesis; supplemental omega-3-rich fish oil, which has been shown to inhibit endothelial expression of Flk-1, a functionally crucial receptor for VEGF, and also can suppress tumor production of pro-angiogenic eicosanoids; high-dose selenium, which has recently been shown to inhibit tumor production of VEGF; green tea polyphenols, which can suppress endothelial responsiveness to both VEGF and fibroblast growth factor; and high-dose glycine, whose recently reported angiostatic activity may reflect inhibition of endothelial cell mitosis, possibly mediated by activation of glycine-gated chloride channels. In light of evidence that tumor-evoked angiogenesis has a high requirement for copper, copper depletion may have exceptional potential as an angiostatic measure, and is most efficiently achieved with the copper-chelating drug tetrathiomolybdate. If logistical difficulties make it difficult to acquire this experimental drug, high-dose zinc supplementation can achieve a slower depletion of the body's copper pool, and in any case can be used as maintenance therapy to maintain an adequate level of copper depletion. A provisional protocol is offered for a nutritionally based MAT entailing a vegan diet and supplemental intakes of fish oil, selenium, green tea polyphenols, glycine, and zinc. Inasmuch as cox-2 is overexpressed in many cancers, and cAMP can boost tumor production of various angiogenic factors as well as autogenous growth factors, adjunctive use of cox-2-specific NSAIDS may be warranted in some cases.",
"title": "A wholly nutritional 'multifocal angiostatic therapy' for control of disseminated cancer."
},
{
"docid": "MED-3241",
"text": "The diagnosis of cancer can motivate survivors to alter their lifestyle habits. Healthcare providers need to be aware of what changes patients are likely to make in order to derive more pertinent recommendations; however, few studies have reported pre- and post-diagnostic lifestyle behaviours. Semi-quantitative food frequency questionnaires (FFQs) completed approximately 1 year after diagnosis were used to evaluate dietary intake and supplement use before and after diagnosis in a cohort of 1,560 breast cancer patients participating in the UK, prospective DietCompLyf study. Intake of fruit and vegetables, wholegrains and lean sources of protein increased significantly post-diagnosis (P < 0.05, each). Conversely, after diagnosis consumption of high-fat, high-sugar products, red meat, coffee, some alcoholic drinks and refined grains significantly decreased (P < 0.05, each). Post-diagnostic changes in diet were accompanied by changes in the intake of macronutrients and a number of vitamins and minerals. Supplement use was highly prevalent (56.1%) pre-diagnosis, increasing to 62.8% after diagnosis (P = 0.001). Fish oils, multivitamin and minerals, and evening primrose oil were most often used and the proportion of users significantly increased (P < 0.05, each) after diagnosis. The percentage of women using oestrogenic botanical supplements (OBSs) was small but more than doubled to 8.4% after diagnosis (P < 0.05). British women participating in the DietCompLyf study reported significant changes in dietary intake and supplement use after their breast cancer diagnosis. These findings contribute to our understanding of female cancer survivors' dietary behaviours which is crucial for developing and implementing recommendations.",
"title": "Significant changes in dietary intake and supplement use after breast cancer diagnosis in a UK multicentre study."
},
{
"docid": "MED-2913",
"text": "The elimination kinetics of polychlorinated biphenyls (PCBs) in humans is difficult to assess in observational studies, because PCB exposure is never completely abolished. In a community with high dietary PCB exposures from whale blubber, we examined two groups of children with increased body burdens from breast-feeding. Follow-up was from ages 4.5 years to 7.5 years (99 subjects) and 7 to 14 years (101 subjects). The calculations were performed by the use of structural equation models, with adjustment for body weight and dietary blubber intake as the main source of postnatal exposure. As a likely result of background exposures, apparent elimination half-lives were unexpectedly long when based on results from all cohort members. Subjects with exposures above the median and in the highest quartile showed half-lives of about 3-4 years for CB-138, and 4.5-5.5 years for CB-105 and CB-118; 6.5-7.5 years for CB-156, CB-170, and CB-187; and 7-9 years for CB-153 and CB-180. The longest half-lives correspond to elimination of the parent PCB solely with a daily fat excretion rate of 1-2 g, while shorter half-lives assume metabolic break-down.",
"title": "Elimination Half-lives of Polychlorinated Biphenyl Congeners in Children"
},
{
"docid": "MED-5095",
"text": "Docosahexaenoic acid (DHA), a long-chain omega-3 fatty acid, is important for eye and brain development and ongoing visual, cognitive, and cardiovascular health. Unlike fish-sourced oils, the bioavailability of DHA from vegetarian-sourced (algal) oils has not been formally assessed. We assessed bioequivalence of DHA oils in capsules from two different algal strains versus bioavailability from an algal-DHA-fortified food. Our 28-day randomized, placebo-controlled, parallel group study compared bioavailability of (a) two different algal DHA oils in capsules (\"DHASCO-T\" and \"DHASCO-S\") at doses of 200, 600, and 1,000 mg DHA per day (n = 12 per group) and of (b) an algal-DHA-fortified food (n = 12). Bioequivalence was based on changes in plasma phospholipid and erythrocyte DHA levels. Effects on arachidonic acid (ARA), docosapentaenoic acid-n-6 (DPAn-6), and eicosapentaenoic acid (EPA) were also determined. Both DHASCO-T and DHASCO-S capsules produced equivalent DHA levels in plasma phospholipids and erythrocytes. DHA response was dose-dependent and linear over the dose range, plasma phospholipid DHA increased by 1.17, 2.28 and 3.03 g per 100 g fatty acid at 200, 600, and 1,000 mg dose, respectively. Snack bars fortified with DHASCO-S oil also delivered equivalent amounts of DHA on a DHA dose basis. Adverse event monitoring revealed an excellent safety and tolerability profile. Two different algal oil capsule supplements and an algal oil-fortified food represent bioequivalent and safe sources of DHA.",
"title": "Bioequivalence of Docosahexaenoic acid from different algal oils in capsules and in a DHA-fortified food."
},
{
"docid": "MED-4951",
"text": "OBJECTIVE: To evaluate the role of the environmental estrogens polychlorinated biphenyls (PCBs) and phthalate esters (PEs) as potential environmental hazards in the deterioration of semen parameters in infertile men without an obvious etiology. DESIGN: Randomized controlled study. SETTING: Tertiary care referral infertility clinic and academic research center. PATIENT(S): Twenty-one infertile men with sperm counts <20 million/mL and/or rapid progressive motility <25% and/or <30% normal forms without evidence of an obvious etiology and 32 control men with normal semen analyses and evidence of conception. Semen and blood samples were obtained as part of the treatment protocol. MAIN OUTCOME MEASURE(S): Evaluation of semen parameters such as ejaculate volume, sperm count, motility, morphology, vitality, osmoregulatory capacity, sperm chromatin stability, and sperm nuclear DNA integrity. RESULT(S): PCBs were detected in the seminal plasma of infertile men but not in controls, and the concentration of PEs was significantly higher in infertile men compared with controls. Ejaculate volume, sperm count, progressive motility, normal morphology, and fertilizing capacity were significantly lower in infertile men compared with controls. The highest average PCB and PE concentrations were found in urban fish eaters, followed by rural fish eaters, urban vegetarians, and rural vegetarians. The total motile sperm counts in infertile men were inversely proportional to their xenoestrogen concentrations and were significantly lower than those in the respective controls. CONCLUSION(S): PCBs and PEs may be instrumental in the deterioration of semen quality in infertile men without an obvious etiology.",
"title": "Role of environmental estrogens in the deterioration of male factor fertility."
},
{
"docid": "MED-2497",
"text": "The birth cohort BraMat (n = 205; a sub-cohort of the Norwegian Mother and Child Cohort Study (MoBa) conducted by the Norwegian Institute of Public Health) was established to study whether prenatal exposure to toxicants from the maternal diet affects immunological health outcomes in children. We here report on the environmental pollutants polychlorinated biphenyls (PCBs) and dioxins, as well as acrylamide generated in food during heat treatment. The frequency of common infections, eczema or itchiness, and periods of more than 10 days of dry cough, chest tightness or wheeze (called wheeze) in the children during the first year of life was assessed by questionnaire data (n = 195). Prenatal dietary exposure to the toxicants was estimated using a validated food frequency questionnaire from MoBa. Prenatal exposure to PCBs and dioxins was found to be associated with increased risk of wheeze and exanthema subitum, and also with increased frequency of upper respiratory tract infections. We found no associations between prenatal exposure to acrylamide and the health outcomes investigated. Our results suggest that prenatal dietary exposure to dioxins and PCBs may increase the risk of wheeze and infectious diseases during the first year of life. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Prenatal exposure to polychlorinated biphenyls and dioxins is associated with increased risk of wheeze and infections in infants."
},
{
"docid": "MED-4937",
"text": "In the late 1960s the first scientific studies on contamination in Antarctica demonstrated the presence of pollutants in Antarctic ecosystems. Many Persistent Organic Pollutants (POPs) are transported globally from the areas in which they are produced and released into the environment in remote areas, including Antarctica. Here we report results obtained concerning the accumulation of polybrominated diphenyl ethers (PBDEs), mono- and non-ortho-polychlorobiphenyls (PCBs), polychlorodibenzodioxins (PCDDs) and polychlorodibenzofurans (PCDFs) in the tissues of two species of Antarctic fish (Chionodraco hamatus and Trematomus bernacchii). The 2,3,7,8-TCDD toxic equivalents (TEQs) were also calculated to evaluate the potential risk of these compounds for the two species. In general, POP levels were higher in the tissues of T. bernacchii than in C. hamatus and the highest concentrations were found in the liver of both species. The PBDE levels varied from 160.5 pg g(-1) wet wt in C. hamatus muscle to 789.9 pg g(-1) wet wt in T. bernacchii liver and were lower than the levels of PCBs. PCBs were the main organochlorine compounds detected and their concentrations ranged from 0.3 ng g(-1) wet wt in C. hamatus muscle to 15.1 ng g(-1) wet wt in T. bernacchii liver. TEQ concentrations resulted higher in C. hamatus than in T. bernacchii and were due mainly to PCDDs. The presence of PBDEs and organochlorine pollutants in the tissues of Antarctic organisms confirms their global transport and distribution.",
"title": "Levels of polybrominated diphenyl ethers (PBDEs) and organochlorine pollutants in two species of Antarctic fish (Chionodraco hamatus and Trematomus..."
},
{
"docid": "MED-2495",
"text": "We investigated whether prenatal exposure from the maternal diet to the toxicants polychlorinated biphenyls (PCBs) and dioxins is associated with the development of immune-related diseases in childhood. Children participating in BraMat, a sub-cohort of the Norwegian Mother and Child Cohort Study (MoBa), were followed in the three first years of life using annual questionnaires (0-3years; n=162, 2-3years; n=180), and blood parameters were examined at three years of age (n=114). The maternal intake of the toxicants was calculated using a validated food frequency questionnaire from MoBa. Maternal exposure to PCBs and dioxins was found to be associated with an increased risk of wheeze and more frequent upper respiratory tract infections. Furthermore, maternal exposure to PCBs and dioxins was found to be associated with reduced antibody response to a measles vaccine. No associations were found between prenatal exposure and immunophenotype data, allergic sensitization and vaccine-induced antibody responses other than measles. Our results suggest that prenatal dietary exposure to PCBs and dioxins may increase the risk of wheeze and the susceptibility to infectious diseases in early childhood. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Prenatal exposure to polychlorinated biphenyls and dioxins from the maternal diet may be associated with immunosuppressive effects that persist int..."
},
{
"docid": "MED-927",
"text": "OBJECTIVE: To assess the effects of krill oil on blood lipids, specifically total cholesterol, triglycerides, low-density lipoprotein (LDL), and high-density lipoprotein (HDL). METHODS: A multi-center, three-month, prospective, randomized study followed by a three-month, controlled follow-up of patients treated with 1 g and 1.5 g krill oil daily. Patients with hyperlipidemia able to maintain a healthy diet and with blood cholesterol levels between 194 and 348 mg per dL were eligible for enrollment in the trial. A sample size of 120 patients (30 patients per group) was randomly assigned to one of four groups. Group A received krill oil at a body mass index (BMI)-dependent daily dosage of 2-3 g daily. Patients in Group B were given 1-1.5 g krill oil daily, and Group C was given fish oil containing 180 mg eicosapentaenoic acid (EPA) and 120 mg docosahexaenoic acid (DHA) per gram of oil at a dose of 3 g daily. Group D was given a placebo containing microcrystalline cellulose. The krill oil used in this study was Neptune Krill Oil, provided by Neptune Technologies and Bioresources, Laval, Quebec, Canada. OUTCOME MEASURES: Primary parameters tested (baseline and 90-day visit) were total blood cholesterol, triglycerides, LDL, HDL, and glucose. RESULTS: Krill oil 1-3 g per day (BMI-dependent) was found to be effective for the reduction of glucose, total cholesterol, triglycerides, LDL, and HDL, compared to both fish oil and placebo. CONCLUSIONS: The results of the present study demonstrate within high levels of confidence that krill oil is effective for the management of hyperlipidemia by significantly reducing total cholesterol, LDL, and triglycerides, and increasing HDL levels. At lower and equal doses, krill oil was significantly more effective than fish oil for the reduction of glucose, triglycerides, and LDL levels.",
"title": "Evaluation of the effects of Neptune Krill Oil on the clinical course of hyperlipidemia."
}
] |
4602
|
As an investing novice, what to do with my money?
|
[
{
"docid": "41357",
"text": "3-5 years is long enough of a timeframe that I'd certainly invest it, assuming you have enough (which $10k is). Even conservatively you can guess at 4-5% annual growth; if you invest reasonably conservatively (60/40 mix of stocks/bonds, with both in large ETFs or similar) you should have a good chance to gain along those lines and still be reasonably safe in case the market tanks. Of course, the market could tank at any time and wipe out 20-30% of that or even more, even if you invest conservatively - so you need to think about that risk, and decide if it's worth it or not. But, particularly if your 3-5 year time frame is reasonably flexible (i.e., if in 2019 the market tanks, you can wait the 2-3 years it may take to come back up) you should be investing. And - as usual, the normal warnings apply. Past performance is not a guarantee of future performance, we are not your investment advisors, and you may lose 100% of your investment...",
"title": ""
},
{
"docid": "466552",
"text": "I'd keep the risk inside the well-funded retirement accounts. Outside those accounts, I'd save to have a proper emergency fund, not based on today's expenses, but on expenses post house. The rest, I'd save toward the downpayment. 20% down, with a reserve for the spending that comes with a home purchase. It's my opinion that 3-5 years isn't enough to put this money at risk.",
"title": ""
},
{
"docid": "422739",
"text": "A lot of people on here will likely disagree with me and this opinion. In my opinion the answer lies in your own motives and intentions. If you'd like to be more cognizant of the market, I'd just dive in and buy a few companies you like. Many people will say you shouldn't pick your own stocks, you should buy an index fund, or this ETF or this much bonds, etc. You already have retirement savings, capital allocation is important there. You're talking about an account total around 10% of your annual salary, and assuming you have sufficient liquid emergency funds; there's a lot of non-monetary benefit to being more aware of the economy and the stock market. But if you find the house you're going to buy, you may have to liquidate this account at a time that's not ideal, possibly at a loss. If all you're after is a greater return on your savings than the paltry 0.05% (or whatever) the big deposit banks are paying, then a high yield savings account is the way I'd go, or a CD ladder. Yes, the market generally goes up but it doesn't ALWAYS go up. Get your money somewhere that it's inured and you can be certain how much you'll have tomorrow. Assuming a gain, the gain you'll see will PALE in comparison to the deposits you'll make. Deposits grow accounts. Consider these scenarios if you allocate $1,000 per month to this account. 1) Assuming an investment return of 5% you're talking about $330 return in the first year (not counting commissions or possible losses). 2) Assuming a high yield savings account at 1.25% you're talking about $80 in the first year. Also remember, both of these amounts would be taxable. I'll admit in the event of 5% return you'll have about four times the gain but you're talking about a difference of ~$250 on $12,000. Over three to five years the most significant contributor to the account, by far, will be your deposits. Anyway, as I'm sure you know this is not investment advice and you may lose money etc.",
"title": ""
},
{
"docid": "219563",
"text": "I'm normally not a fan of partitioning investment money into buckets but your case may be the clearest case for it I've seen in awhile. Your income and saving is good and you have two clearly defined goals of retirement saving and saving for a house each with very different time frames ~30 years and 3-5 years respectively. For medium term money, like saving for a house, just building up cash is not actually a bad idea. This minimizes the chance that a market crash will happen at the same time you need to withdraw the money. However, given you have the means to take more risk a generally smarter scheme would be to invest much of the money in a broad liquid bond funds with a somewhat lower percentage in stocks and then reduce the amount of stock each year as you get closer even moving some into cash. This gives reasonable positive expected return while lowering the risk of having to sell during a crisis as the time to purchase gets shorter and shorter. The retirement money should be invested for the long term as usual. A majority in low-fee index stock funds/etfs is the standard advice for good reason.",
"title": ""
}
] |
[
{
"docid": "35518",
"text": "Alright so you have $12,000 and you want to know what to do with it. The main thing here is, you're new to investments. I suggest you don't do anything quick and start learning about the different kinds of investment options that can be available to you with returns you might appreciate. The most important questions to ask yourself is what are your life goals? What kind of financial freedom do you want, and how important is this $12,000 dollars to you in achieving your life goals. My best advice to you and to anyone else who is looking for a place to put their money in big or small amounts when they have earned this money not from an investment but hard work is to find a talented and professional financial advisor. You need to be educated on the options you have, and keep them in lines of what risks you are willing to take and how important that principal investment is to you. Investing your money is not easy at all, and novices tend to lose their money a lot. The same way you would ask a lawyer for law advice, its best to consult a financial planner for advice, or so they can invest that money for you.",
"title": ""
},
{
"docid": "382415",
"text": "\"There's not nearly enough information here for anyone to give you good advice. Additionally, /r/personalfinance will probably be a bit more relevant and helpful for what you're asking. Aside from that, if you don't know what you're doing, stay out of currency trading and mutual funds. If you don't care about losing your money, go right ahead and play in some markets, but remember there are people paid millions of dollars/year who don't make consistent profit. What are the chances a novice with no training will perform well? My $.02, pay your debt, make a general theory about the economy a year from now (e.g. \"\"Things will be worse in Europe than they are now\"\") and then invest your money in an index fund that matches that goal (e.g. Some sort of Europe-Short investment vehicle). Reassess a year from now and don't stress about it.\"",
"title": ""
},
{
"docid": "170594",
"text": "You might want to just keep it in cash. For one step further you could do an even split of USD, EUR and silver. USD hedges against loss of value in the euro, precious metal hedges against a global financial problem. Silver over gold because of high gold:silver ratio is high. You could lose money this way. There are some bad things that can happen that will make your portfolio fall, but there are also many bad things that can happen that would result in no change or gain. With careful trades in stocks and even more aggressive assets, you could conceivably see large returns. But since you're novice, you won't be able to make these trades, and you'll just lose your investment. Ordinarily, novices can buy an S&P ETF and enjoy decent return (7-8% annual on average) at reasonable risk, but that only works if you stay invested for many years. In the short term, S&P can crash pretty badly, and stay low for a year or more. If you can just wait it out, great (it has always recovered eventually), but if some emergency forces you to take the money out you'd have to do so at a big loss. Lately, the index has shown signs of being overvalued. If you buy it now, you could luck out and be 10-15% up in a year, but you could also end up 30% down - not a very favorable risk/reward rate. Which is why I would hold on to my cash until it does crash (or failing that, starts looking more robust again) and then think about investing.",
"title": ""
},
{
"docid": "535737",
"text": "If your investment returns are the main variable you use to determine if your advisor is doing a good job you are using his or her services incorrectly Also, if you are using a good advisor, he or she needs to know how your investments are doing, not you. However, my thoughts are based on the idea that you can't go it alone. If you are not among the people concerned about the market, waiting for the market to go down 'so you can find a better buying opportunity', or making one of many other novice mistakes, I'm not speaking directly to you with my comments.",
"title": ""
},
{
"docid": "216757",
"text": "\"Great question! While investing in individual stocks can be very useful as a learning experience, my opinion is that concentrating an entire portfolio in a few companies' stock is a mistake for most investors, and especially for a novice for several reasons. After all, only a handful of professional investors have ever beaten the market over the long term by picking stocks, so is it really worth trying? If you could, I'd say go work on Wall Street and good luck to you. Diversification For many investors, diversification is an important reason to use an ETF or index fund. If they were to focus on a few sectors or companies, it is more likely that they would have a lop-sided risk profile and might be subject to a larger downside risk potential than the market as a whole, i.e. \"\"don't put all your eggs in one basket\"\". Diversification is important because of the nature of compound investing - if you take a significant hit, it will take you a long time to recover because all of your future gains are building off of a smaller base. This is one reason that younger investors often take a larger position in equities, as they have longer to recover from significant market declines. While it is very possible to build a balanced, diversified portfolio from individual stocks, this isn't something I'd recommend for a new investor and would require a substantial college-level understanding of investments, and in any case, this portfolio would have a more discrete efficient frontier than the market as a whole. Lower Volatility Picking individual stocks or sectors would could also significantly increase or decrease the overall volatility of the portfolio relative to the market, especially if the stocks are highly cyclical or correlated to the same market factors. So if they are buying tech stocks, they might see bigger upswings and downswings compared to the market as a whole, or see the opposite effect in the case of utilities. In other words, owning a basket of individual stocks may result in an unintended volatility/beta profile. Lower Trading Costs and Taxes Investors who buy individual stocks tend to trade more in an attempt to beat the market. After accounting for commission fees, transaction costs (bid/ask spread), and taxes, most individual investors get only a fraction of the market average return. One famous academic study finds that investors who trade more trail the stock market more. Trading also tends to incur higher taxes since short term gains (<1 year) are taxed at marginal income tax rates that are higher than long term capital gains. Investors tend to trade due to behavioral failures such as trying to time the market, being overconfident, speculating on stocks instead of long-term investing, following what everyone else is doing, and getting in and out of the market as a result of an emotional reaction to volatility (ie buying when stocks are high/rising and selling when they are low/falling). Investing in index funds can involve minimal fees and discourages behavior that causes investors to incur excessive trading costs. This can make a big difference over the long run as extra costs and taxes compound significantly over time. It's Hard to Beat the Market since Markets are Quite Efficient Another reason to use funds is that it is reasonable to assume that at any point in time, the market does a fairly good job of pricing securities based on all known information. In other words, if a given stock is trading at a low P/E relative to the market, the market as a whole has decided that there is good reason for this valuation. This idea is based on the assumption that there are already so many professional analysts and traders looking for arbitrage opportunities that few such opportunities exist, and where they do exist, persist for only a short time. If you accept this theory generally (obviously, the market is not perfect), there is very little in the way of insight on pricing that the average novice investor could provide given limited knowledge of the markets and only a few hours of research. It might be more likely that opportunities identified by the novice would reflect omissions of relevant information. Trying to make money in this way then becomes a bet that other informed, professional investors are wrong and you are right (options traders, for example). Prices are Unpredictable (Behave Like \"\"Random\"\" Walks) If you want to make money as a long-term investor/owner rather than a speculator/trader, than most of the future change in asset prices will be a result of future events and information that is not yet known. Since no one knows how the world will change or who will be tomorrow's winners or losers, much less in 30 years, this is sometimes referred to as a \"\"random walk.\"\" You can point to fundamental analysis and say \"\"X company has great free cash flow, so I will invest in them\"\", but ultimately, the problem with this type of analysis is that everyone else has already done it too. For example, Warren Buffett famously already knows the price at which he'd buy every company he's interested in buying. When everyone else can do the same analysis as you, the price already reflects the market's take on that public information (Efficent Market theory), and what is left is the unknown (I wouldn't use the term \"\"random\"\"). Overall, I think there is simply a very large potential for an individual investor to make a few mistakes with individual stocks over 20+ years that will really cost a lot, and I think most investors want a balance of risk and return versus the largest possible return, and don't have an interest in developing a professional knowledge of stocks. I think a better strategy for most investors is to share in the future profits of companies buy holding a well-diversified portfolio for the long term and to avoid making a large number of decisions about which stocks to own.\"",
"title": ""
},
{
"docid": "493671",
"text": "\"i'm absolutely a newcomer in economics and i wish to understand how things work around finance. This is a pretty loaded question. To understand finance, you need the basics of economics. In almost every economics school in the country, you first study microeconomics and then economics. So, we'll start with micro. One of, if not the, most popular books is \"\"Principles of Microeconomics\"\" by Mankiw. This book covers the fundamentals of micro econ (opportunity, supply, demand, consumer choice, production, costs, basic game theory, and allocation of resources) in a clear and effective manner. It's designed for the novice and very easy to read. Like Mankiw's other book, \"\"Principles of Macroeconomics\"\" is also top notch. There is some overlap in key areas (i.e. opportunity cost, supply, demand, indifference curves, elasticity, taxation) because they are fundamental to economics and the overlap will always be there, but from there the book goes into key macro concepts like GDP, CPI, Employment, Monetary and Fiscal policy, and Inflation. An excellent intro primer indeed. Now that you have the fundamentals down, it's time to learn about finance. The best resource, in my opinion, is \"\"Financial Markets\"\" by Robert Shiller on Open Yale Courses. I've personally taken Prof. Shiller's class last semester, and the man is brilliant. The lectures cover every single aspect of finance and can turn the complete novice into a fairly experienced finance student. The first lecture also covers all the math required so you don't get lost at any point. Be warned, however, that the course is very deep. We used Fabozzi's textbook \"\"Foundations of Financial Markets and Institutions,\"\" which is over 600 pages deep and we were required to know essentially all of it. Watch the videos and follow the readings and you'll be a finance whiz soon! Financial Markets on Open Yale And that's your roadmap to what you want. There are other economics books and it's true that the first few chapters of both Mankiw books are largely the same, but that's because any economics course always covers the basics first. If you want to look at other books, Krugman has written some good books as well. Be sure to read reviews because some books are meant for 2nd/3rd year econ students, so you don't want to get a too advanced book. At the novice level, we're interested in understanding the basic concepts so we can master Fabozzi. As for finance books - Fabozzi teaches you all the fundamentals of financial markets so you've got a powerful foundation. From there you can expand to more niche books such as books on investing or on monetary policy or whatever you want. Best of luck!\"",
"title": ""
},
{
"docid": "214174",
"text": "\"A Roth IRA is simply a tax-sheltered account that you deposit funds into, and then invest however you choose (within the limits of the firm you deposit the funds with). For example, you could open a Roth IRA account with Vanguard. You could then invest the $3000 by purchasing shares of VOO, which tracks the S&P 500 index and has a very low expense ratio (0.04 as of last time I checked). Fidelity has a similar option, or Schwab, or whatever brokerage firm you prefer. IRAs are basically just normal investment accounts, except they don't owe taxes until you withdraw them (and Roth don't even owe them then, though you paid taxes on the funds you deposit). They have some limitations regarding options trading and such, but if you're a novice investor just looking to do basic investments, you'll not notice. Then, your IRA would go up or down in value as the market went up or down in value. You do have some restrictions on when you can withdraw the funds; Roth IRA has fewer than a normal IRA, as you can withdraw the capital (the amount you deposited) without penalty, but the profits cannot be withdrawn until you're retirement age (I won't put an actual year, as I suspect that actual year will change by the time you're that old; but think 60s). The reason not to invest in an IRA is if you plan on using the money in the near future - even as an \"\"emergency fund\"\". You should have some money that is not invested aggressively, that is in something very safe and very accessible, for your emergency fund; and if you plan to buy a house or whatever with the funds, don't start an IRA. But if this is truly money you want to save for retirement, that's the best place to start. **Note, this is not investment advice, and you should do your own homework prior to making any investment. You can lose some or all of the value of your account while investing.\"",
"title": ""
},
{
"docid": "406711",
"text": "No, SPDR ETFs are not a good fit for a novice investor with a low level of financial literacy. In fact, there is no investment that is safe for an absolute beginner, not even a savings account. (An absolute beginner could easily overdraw his savings account, leading to fees and collections.) I would say that an investment becomes a good fit for an investor as soon as said investor understands how the investment works. A savings account at a bank or credit union is fairly easy to understand and is therefore a suitable place to hold money after a few hours to a day of research. (Even after 0 hours of research, however, a savings account is still better than a sock drawer.) Money market accounts (through a bank), certificates of deposit (through a bank), and money market mutual funds (through a mutual fund provider) are probably the next easiest thing to understand. This could take a few hours to a few weeks of research depending on the learner. Equities, corporate bonds, and government bonds are another step up in complexity, and could take weeks or months of schooling to understand well enough to try. Equity or bond mutual funds -- or the ETF versions of those, which is what you asked about -- are another level after that. Also important to understand along the way are the financial institutions and market infrastructure that exist to provide these products: banks, credit unions, public corporations, brokerages, stock exchanges, bond exchanges, mutual fund providers, ETF providers, etc.",
"title": ""
},
{
"docid": "169004",
"text": "Basically there are 2 ways you can make money from an investment, through income (eg: rent or dividends) and through the price of the investment going up (capital growth or gains). Most people associate negative gearing with investment properties but it can be done with shares and other investments where you borrow money to buy the investment and it produces an income of some sort. If the investment does not produce an income then you cannot negative gear it. Using a property as an example (in Australia), if all your expenses each month (loan interest payments, council and water rates, insurance and/or strata, advertising and management fees, depreciation, and maintenance expense) are greater than your income (rent), then you are negative gearing the investment property. This is a monthly loss on your investment which can be used to offset and reduce the amount of tax you pay during the year. So most people negative gearing an investment property will get a nice sum back when they do their tax returns. The problem with negative gearing is that you have to lose money in order to save some tax. So as an example, if you are on a marginal tax rate of 30%, for every $1 you lose from the investment property you will save 30c in tax. If your marginal tax rate is 45% then will save 45c in tax for every $1 lost on the investment property. Thus negative gearing becomes more tax effective the higher your income (and tax bracket). But you are still losing money overall. The problem is that most novice investors buy an investment property for the main purpose of reducing their taxes. This can be dangerous because the main reason to buy any investment should be that you consider it to be a good investment, not to save you tax. Because if the investment is not a good one, then you will not only lose money on the income side but also on the capital side. Negative gearing should be looked at as a bonus or additional benefit when chosing a good investment to buy, not as the reason to buy the investment.",
"title": ""
},
{
"docid": "379546",
"text": "It sounds like you are interested in investing in the stock market but you don't want to take too much risk. Investing in an Index EFT will provide some diversification and can be less risky than investing in individual stocks, however with potentially lower returns. If you want to invest your money, the first thing you should do is learn about managing your risk. You are still young and you should spend your time now to increase your education and knowledge. There are plenty of good books to start with, and you should prepare an investment plan which incorporates a risk management strategy. $1000 is a little low to start investing in the stock market, so whilst you are building your education and preparing your plan, you can continue building up more funds for when you are ready to start investing. Place your funds in an high interest savings account for now, and whilst you are learning you can practice your strategies using virtual accounts. In fact the ASX has a share market game which is held 2 or 3 times per year. The ASX website also has some good learning materials for novices and they hold regular seminars. It is another good source for improving your education in the subject. Remember, first get educated, then plan and practice, and then invest.",
"title": ""
},
{
"docid": "199181",
"text": "If you are a novice investor and want to diversify, I'd recommend looking into targeted mutual funds. They couldn't be easier. You just put your money in the fund with the year that you anticipating needing to take the money out and the fund manager handles diversification and adjusting the risk appropriately over the life of the fund based on the remaining time horizon. The only downside is that the annual expenses tend to be higher on these than if you just invested in the underlying securities/funds, but you are pretty much paying them to manage it for you.",
"title": ""
},
{
"docid": "564475",
"text": "\"You can file an LLC yourself in most states, although it might be helpful to use a service if you're not sure what to do to ensure it is correct. I filed my LLC here in Colorado online with the Secretary of State's office, which provided the fill-in-the-blank forms and made it easy. In the U.S., taxation of an LLC is \"\"pass-through\"\", meaning the LLC itself does not have any tax liability. Taxes are based on what you take out of the LLC as distributions to yourself, so you pay personal income tax on that. There are many good books on how to form and then operate an LLC, and I personally like NoLo (link to their web site) because they cater to novices. As for hiring people in India, I can't speak to that, so hopefully someone else can answer that specific topic. As for what you need to know about how to run it, I'll refer back to the NoLo books and web site.\"",
"title": ""
},
{
"docid": "206298",
"text": "Your question is actually quite broad, so will try to split it into it's key parts: Yes, standard bank ISAs pay very poor rates of interest at the moment. They are however basically risk free and should track inflation. Any investment in the 6-7% return range at the moment will be linked to stock. Stock always carries large risks (~50% swings in capital are pretty standard in the short run. In the long run it generally beats every other asset class by miles). If you can’t handle those types of short terms swings, you shouldn’t get involved. If you do want to invest in stock, there is a hefty ignorance tax waiting at every corner in terms of how brokers construct their fees. In a nutshell, there is a different best value broker in the UK for virtually every band of capital, and they make their money through people signing up when they are in range x, and not moving their money when they reach band y; or just having a large marketing budget and screwing you from the start (Nutmeg at ~1% a year is def in this category). There isn't much of an obvious way around this if you are adamant you don't want to learn about it - the way the market is constructed is just a total predatory minefield for the complete novice. There are middle ground style investments between the two extremes you are looking at: bonds, bond funds and mixes of bonds and small amounts of stock (such as the Vanguard income or Conservative Growth funds outlined here), can return more than savings accounts with less risk than stocks, but again its a very diverse field that's hard to give specific advice about without knowing more about what your risk tolerance, timelines and aims are. If you do go down this (or the pure stock fund) route, it will need to be purchased via a broker in an ISA wrapper. The broker charges a platform fee, the fund charges a fund fee. In both cases you want these as low as possible. The Telegraph has a good heat map for the best value ISA platform providers by capital range here. Fund fees are always in the key investor document (KIID), under 'ongoing charges'.",
"title": ""
},
{
"docid": "233732",
"text": "One possibility would be to invest in a crude oil ETF (or maybe technically they're an ETP), which should be easily accessible through any stock trading platform. In theory, the value of these investments is directly tied to the oil price. There's a list of such ETFs and some comments here. But see also here about some of the problems with such things in practice, and some other products aiming to avoid those issues. Personally I find the idea of putting all my savings into such a vehicle absolutely horrifying; I wouldn't contemplate having more than a small percentage of a much more well diversified portfolio invested in something like that myself, and IMHO it's a completely unsuitable investment for a novice investor. I strongly suggest you read up on topics like portfolio construction and asset allocation (nice introductory article here and here, although maybe UK oriented; US SEC has some dry info here) before proceeding further and putting your savings at risk.",
"title": ""
},
{
"docid": "234196",
"text": "I was thinking that. However, again sorry for the novice questions. Would I be better off getting a manager for the area, or just finding employees willing to work/contact me on a daily basis and I would manage from a different state? I mean the former would make sense to me but what do I know, never owned a business before.",
"title": ""
},
{
"docid": "84870",
"text": "My interpretation of that sentence is that you can't do the buying/selling of shares outright (sans margin) because of the massive quantity of shares he's talking about. So you have to use margin to buy the stocks. However, because in order to make significant money with this sort of strategy you probably need to be working dozens of stocks at the same time, you need to be familiar with portfolio margin. Since your broker does not calculate margin calls based on individual stocks, but rather on the value of your whole portfolio, you should have experience handling margin not just on individual stock movements but also on overall portfolio movements. For example, if 10% (by value) of the stocks you're targeting tend to have a correlation of -0.8 with the price of oil you should probably target another 10% (by value) in stocks that tend to have a correlation of +0.8 with the price of oil. And so on and so forth. That way your portfolio can weather big (or even small) changes in market conditions that would cause a margin call on a novice investor's portfolio.",
"title": ""
},
{
"docid": "475273",
"text": "If someone invest certain amount on my company and after a year I am able to return the exact capital with the profit, what will I do to that investor? Did the investor receive shares in the company for the money that was invested in the company? This is the big question here as if so then there isn't the need to return the money but rather grow the business so that the investor's shares are worth more. Will that person still invest in my company? You may need to consider what you mean by invest as generally there are a couple of ways to finance a business: Equity - Ownership of the company is sold to raise money to run the company. Debt - The company is lent money that is to be repaid over time. Investing is usually the first case not the second. What if I have enough profit to continue my business, do I still need that investor? You wouldn't need the investor. However, you may want that investor as they could provide more funds, connections or other benefits to the company that may be worth considering here.",
"title": ""
},
{
"docid": "67625",
"text": "It appears your company is offering roughly a 25% discount on its shares. I start there as a basis to give you a perspective on what the 30% matching offer means to you in terms of value. Since you are asking for things to consider not whether to do it, below are a few considerations (there may be others) in general you should think about your sources of income. if this company is your only source of income, it is more prudent to make your investment in their shares a smaller portion of your overall investment/savings strategy. what is the holding period for the shares you purchase. some companies institute a holding period or hold duration which restricts when you can sell the shares. Generally, the shorter the duration period the less risk there is for you. So if you can buy the shares and immediately sell the shares that represents the least amount of relative risk. what are the tax implications for shares offered at such a discount. this may be something you will need to consult a tax adviser to get a better understanding. your company should also be able to provide a reasonable interpretation of the tax consequences for the offering as well. is the stock you are buying liquid. liquid, in this case, is just a fancy term for asking how many shares trade in a public market daily. if it is a very liquid stock you can have some confidence that you may be able to sell out of your shares when you need. personally, i would review the company's financial statements and public statements to investors to get a better understanding of their competitive positioning, market size and prospects for profitability and growth. given you are a novice at this it may be good idea to solicit the opinion of your colleagues at work and others who have insight on the financial performance of the company. you should consider other investment options as well. since this seems to be your first foray into investing you should consider diversifying your savings into a few investments areas (such as big market indices which typically should be less volatile). last, there is always the chance that your company could fail. Companies like Enron, Lehman Brothers and many others that were much smaller than those two examples have failed in the past. only you can gauge your tolerance for risk. As a young investor, the best place to start is to use index funds which track a broader universe of stocks or bonds as the first step in building an investment portfolio. once you own a good set of index funds you can diversify with smaller investments.",
"title": ""
},
{
"docid": "5223",
"text": "Are you one who cannot invest high efforts and time to enhance the profit in trading? However, you have strong desire to gain profits in trading binary options. Then, binary today is just for you. It encompasses the features, which is highly applicable for novice and experience person.",
"title": ""
},
{
"docid": "503742",
"text": "\"I have been a landlord in Texas for just over 3 years now. I still feel like a novice, but I will give you the benefit of my experience. If you are relying on rental properties for current income versus a long term return you are going to have to do a good job at shopping for bargains to get monthly cash flow versus equity growth that is locked up in the property until you sell it. If you want to pull a lot of cash out of a property on a regular basis you probably are going to have to get into flipping them, which is decidedly not passive investing. Also, it is easy to underestimate the expenses associated with rental properties. Texas is pretty landlord friendly legally, however it does have higher than usual property taxes, which will eat into your return. Also, you need to factor in maintenance, vacancy, tenant turnover costs, etc. It can add up to a lot more than you would expect. If you are handy and can do a lot of repairs yourself you can increase your return, but that makes it less of a passive investment. The two most common rules I have heard for initially evaluating whether an investment property is likely to be cash flow positive are the 1% and 50% rules. The 1% rule says the expected monthly rent needs to be 1% or greater of the purchase price of the house. So your hypothetical $150K/$10K scenario doesn't pass that test. Some people say this rule is 2% for new landlords, but in my experience you'd have to get lucky in Texas to find a house priced that competitively that didn't need a lot of work to get rents that high. The 50% rule says that the rent needs to be double your mortgage payment to account for expenses. You also have to factor in the hassle of dealing with tenants, the following are not going to happen when you own a mutual fund, but are almost inevitable if you are a landlord long enough: For whatever reason you have to go to court and evict a tenant. A tenant that probably lost their job, or had major medical issues. The nicest tenant you ever met with the cutest kids in the world that you are threatening to make homeless. Every fiber of your being wants to cut them some slack, but you have a mortgage to pay and can't set an expectation that paying the rent on time is a suggestion not a rule. or the tenant, who seemed nice at first, but now considers you \"\"the man\"\" decides to fight the eviction and won't move out. You have to go through a court process, then eventually get the Sheriff to come out and forcibly remove them from the property, which they are treating like crap because they are mad at you. All the while not paying rent or letting you re-let the place. The tenant isn't maintaining the lawn and the HOA is getting on your butt about it. Do you pay someone to mow the grass for them and then try to squeeze the money out of the tenant who \"\"never agreed to pay for that\"\"? You rent to a college kid who has never lived on their own and has adopted you as their new parent figure. \"\"The light in the closet went out, can you come replace the bulb?\"\" Tenants flat out lying to your face. \"\"Of course I don't have any pets that I didn't pay the deposit for!\"\" (Pics all over facebook of their kids playing with a dog in the \"\"pet-free\"\" house)\"",
"title": ""
},
{
"docid": "498631",
"text": "\"Do I need an Investment Adviser? No, but you may want to explore the idea of having one. Is he going to tell me anything that my accountant can't? Probably. How much expertise are you expecting from your accountant here? Do you think your accountant knows everything within the realms of money from taxes, insurance products, investments and all your choices and what would work or wouldn't? Seems like it could be a tall order to my mind. My accountant did say to come to him for advice on investment/business issues. So, he is willing, but is he able? Not asking about his competence, but rather \"\"is there something that only an Investment Adviser can provide, by law, that an accountant can't\"\"? Not that I know though don't forget how much expertise are you expecting here from one person. Is this person intended to answer all your money questions? But isn't that something that my accountant could/should do? Perhaps though how well are you expecting one person to be aware of so much stuff? I want you to know all the tax law so I can minimize taxes, maximize my investment returns, cover me with adequate insurance, and protect my savings seems like a bit much to put on one entity. Do I need either of them? Won't the Internet and sites like this one suffice? Need no. However, how much time are you prepared to spend learning the basics of strategies that work for you? How much money are you prepared to put into things to learn what works and doesn't? While it is your decision, consider how to what extent do you diagnose your medical issues through the internet versus going to see a doctor? Be careful of how much of a do it yourself approach you want to go here and recognize that there are multiple approaches that may work. The question is which trade-offs are OK for you.\"",
"title": ""
},
{
"docid": "319928",
"text": "I switched from engineering into finance, into an entry level position as an analyst on the investment side. I can tell you about my experience and how I did it. Yes, it is incredibly hard to get a position on the buyside. Investment management doesn't scale well with numbers, adding more analysts typically doesn't improve results (i.e. Buffett and Munger made all the investment decisions at Berkshire Hathaway, the most successful investment team is a two man team running more than a hundred billion dollars of assets). So teams are very small. A large amount of money goes through the hands of very few people, so naturally the pay is very big. The recruiters are not lying when they say there are hundreds of applicants chasing each one of those jobs. I tried asking my friends and family, but being a first generation American, most of the people I know are blue-collar types that work with their hands. I had some success tapping into the alumni network, I got many responses with advice but no interviews. It doesn't help that the finance world is currently shrinking and there are talented people losing their jobs. I had the most success attending my schools career fair. If you graduated from one of the top schools, the firms that are recruiting will still show up. Also, check your schools career office. All the top schools I know of have on-campus interviews. They are generally open to alumni. It is summer right now, but on-campus recruiting season will start in the fall. You should be able to get some interviews through your school. Now the most important thing you need to do is to differentiate yourself. What are you doing right now? Are you working in some other area of finance or a different field altogether? I think the best way to do it (and it is how I did it) is to invest your own money. If you are in an interview and you say you invest your own money, you are pretty much guaranteed that you will be explaining one of your investment theses for the next half hour. This is effectively what you will be doing in the real job if you get it. Firms want to hire someone who can start working, they don't want to pay you that big money only to find that you can't do anything for the next year or two before they cut you. So you have to prove that you can do the job. Interns do it by working for cheap for a summer or two. Someone who graduated already can do it by claiming that they do it on the side, and then backing that up by being able to explaining positions intelligently (you will NOT get the job if it looks anything like /r/investing). There is also something hypocritical if you say that you should be paid boatloads of money because you are capable of managing money well (that is what you are claiming by applying to an investment job) and you don't manage your own money and you haven't formulated any investment theses. Students typically won't be able to do this because they don't have any money to invest, so they get their jobs through the internship route.",
"title": ""
},
{
"docid": "188596",
"text": "You are always best off investing in things you understand. If you have a deep understanding of the aeronautical industry, say, you are a Vice President at Boeing and have been working at Boeing for 40 years, then that would be a reason for investing in that sector: because you may be able to better evaluate different companies in that sector. If you are a novice in the sector, or just have an amateur interest in it, then it may not be a good idea, because your knowledge may not be sufficient to give you much of an advantage. Before focusing on one investment of any type, industry sector based, or otherwise, you want to ask yourself: am I an expert in this subject? The answer to that question will have a big impact on your success.",
"title": ""
},
{
"docid": "133935",
"text": "\"I have money to invest. Where should I put it? Anyone who answers with \"\"Give it to me, I'll invest it for you, don't worry.\"\" needs to be avoided. If your financial advisor gives you this line or equivalent, fire him/her and find another. Before you think about where you should put your money, learn about investing. Take courses, read books, consume blogs and videos on investing in stocks, businesses, real estate, and precious metals. Learn what the risks and rewards are for each, and make an informed decision based on what you learned. Find differing opinions on each type of investment and come to your own conclusions for each. I for example, do not understand stocks, and so do not seriously work the stock market. Mutual funds make money for the folks selling them whether or not the price goes up or down. You assume all the risk while the mutual fund advisor gets the reward. If you find a mutual fund advisor who cannot recommend the purchase of a product he doesn't sell, he's not an advisor, he's a salesman. Investing in business requires you either to intimately understand businesses and how to fund them, or to hire someone who can make an objective evaluation for you. Again this requires training. I have no such training, and avoid investing in businesses. Investing in real estate also requires you to know what to look for in a property that produces cash flow or capital gains. I took a course, read some books, gained experience and have a knowledgeable team at my disposal so my wins are greater than my losses. Do not be fooled by people telling you that higher risk means higher reward. Risks that you understand and have a detailed plan to mitigate are not risks. It is possible to have higher reward without increasing risk. Again, do your own research. The richest people in the world do not own mutual funds or IRAs or RRSPs or TFSAs, they do their own research and invest in the things I mentioned above.\"",
"title": ""
},
{
"docid": "129255",
"text": "Investing is really about learning your own comfort level. You will make money and lose money. You will make mistakes but you will also learn a great deal. First off, invest in your own financial knowledge, this doesn't require capital at all but a commitment. No one will watch or care for your own money better than yourself. Read books, and follow some companies in a Google Finance virtual portfolio. Track how they're doing over time - you can do this as a virtual portfolio without actually spending or losing money. Have you ever invested before? What is your knowledge level? Investing long term is about trying to balance risk while reducing losses and trying not to get screwed along the way (by people). My personal advice: Go to an independent financial planner, go to one that charges you per hour only. Financial planners that don't charge you hourly get paid in commissions. They will be biased to sell you what puts the most money in their pockets. Do not go to the banks investment people, they are employed by the banks who have sales and quota requirements to have you invest and push their own investment vehicles like mutual funds. Take $15k to the financial planner and see what they suggest. Keep the other $5K in something slow and boring and $1k under your mattress in actual cash as an emergency. While you're young, compound interest is the magic that will make that $25k increase hand over fist in time. But you need to have it consistently make money. I'm young too and more risk tolerant because I have time. While I get older I can start to scale back my risk because I'm nearing retirement and preserve instead of try to make returns.",
"title": ""
},
{
"docid": "136307",
"text": "I like to put money I am going to spend in my Quicken register (similar to Money in my limited experience) and that is the big ticket feature missing from mint.com. Mint.com can only tell you what you did, or in a very general sense what you plan to do. As a register, mint.com is flexible enough for me to categorize my transactions. As a planning / budgeting tool mint.com is very simple and fast to get going, but lacks the depth of a budget I want to manage every week. Mint.com also tracks my investments, but I freely admit my investment management is nothing more than putting money into the same accounts. I bother with investment tracking other than looking to see it isn't zero. I say try mint.com. Mint.com has a place to totally delete your account.",
"title": ""
},
{
"docid": "410322",
"text": "\"Since I, personally, agree with the investment thesis of Peter Schiff, I would take that sum and put it with him in a managed account, and leave it there. I'm not sure how to find a firm that you like the investment strategy of. I think that it's too complicated to do as a side thing. Someone needs to be spending a lot of time researching various instruments and figuring out what is undervalued or what is exposed to changing market trends or whatever. I basically just want to give my money to someone and say \"\"I agree with your investment philosophy, let me pay you to manage my money, too.\"\" No one knows who is right, of course. I think Schiff is right, so that's where I would put the amount of money you're talking about. If you disagree with his investment philosophy, this doesn't really make any sense to do. For that amount of money, though, I think firms would be willing to sit down with you and sell you their services. You could ask them how they would diversify this money given the goals that you have for it, and pick one that you agree with the most.\"",
"title": ""
},
{
"docid": "582161",
"text": "\"As others have pointed out, leveraged investing is investing borrowed money. To do so, you need to convince a lender that you're good for the loan. This usually means you need to have collateral worth what you're trying to borrow, or you need to pay a higher rate to account for the fact that they're gambling that you will remain employed and pay off the loan. Leveraged investing is, in general, a risky move for exactly this reason. You can lose not just your original investment, but everything you borrowed as well. The only time it really makes sense, in my admittedly conservative opinion, is when you (a) can afford to suffer that loss, (b) are pretty confident of your investment, and (c) have assets which you have no intention to sell for the duration of the loan. An \"\"unneeded\"\" mortgage on a house is a classic example, thusly: When I purchased my house, I had enough savings that I could have bought it without taking a mortgage. Instead, I took out a mortgage for a large part of that, and left the remainder in my investment accounts -- essentially building the leveraging loan into the mortgage. I then got obscenely \"\"lucky\"\" when interest rates fell through the floor due to the Great Recession, and was able to refinance the mortgage to near record low rates. As a result, on that loan -- which, as I say, I'm in the position of being able to pay off at any time without killing my finances -- I'm currently paying about 3.5%, while the cash this has let me leave in my investments is earning several times that... a net win. But again, note that this required collateral. Essentially, all I'm doing is paying a bit to to borrow my own money (part of the value of the house). There really is no easy way to \"\"convert 25k to 250k\"\" -- if there was, everyone would be doing it. There's no magic in investment. Just time and compounding returns and trading off risk against potential gain. The more you try to push it and win big, the more you risk losing big. I really recommend not attempting anything fancy until you're wealthy enough that you can afford those losses. But if you insist on playing in this space, the answer to your question is to buy options. Options are a packaged form of borrowing to invest. Note that they're still considered high-risk unless you know EXACTLY what you're doing, and again I strongly recommend you not put money into them unless you can afford to lose it -- options have a nasty habit of turning from apparent gains on paper to losses remarkably quickly.\"",
"title": ""
},
{
"docid": "473949",
"text": "\"Many of my friends said I should invest my money on stocks or something else, instead of put them in the bank forever. I do not know anything about finance, so my questions are: First let me say that your friends may have the best intentions, but don't trust them. It has been my experience that friends tell you what they would do if they had your money, and not what they would actually do with their money. Now, I don't mean that they would be malicious, or that they are out to get you. What I do mean, is why would you take advise from someone about what they would do with 100k when they don't have 100k. I am in your financial situation (more or less), and I have friends that make more then I do, and have no savings. Or that will tell you to get an IRA -so-and-so but don't have the means (discipline) to do so. Do not listen to your friends on matters of money. That's just good all around advise. Is my financial status OK? If not, how can I improve it? Any financial situation with no or really low debt is OK. I would say 5% of annual income in unsecured debt, or 2-3 years in annual income in secured debt is a good place to be. That is a really hard mark to hit (it seems). You have hit it. So your good, right now. You may want to \"\"plan for the future\"\". Immediate goals that I always tell people, are 6 months of income stuck in a liquid savings account, then start building a solid investment situation, and a decent retirement plan. This protects you from short term situations like loss of job, while doing something for the future. Is now a right time for me to see a financial advisor? Is it worthy? How would she/he help me? Rather it's worth it or not to use a financial adviser is going to be totally opinion based. Personally I think they are worth it. Others do not. I see it like this. Unless you want to spend all your time looking up money stuff, the adviser is going to have a better grasp of \"\"money stuff\"\" then you, because they do spend all their time doing it. That being said there is one really important thing to consider. That is going to be how you pay the adviser. The following are my observations. You will need to make up your own mind. Free Avoid like the plague. These advisers are usually provided by the bank and make their money off commission or kickbacks. That means they will advise you of the product that makes them the most money. Not you. Flat Rate These are not a bad option, but they don't have any real incentive to make you money. Usually, they do a decent job of making you money, but again, it's usually better for them to advise you on products that make them money. Per Hour These are my favorite. They charge per hour. Usually they are a small shop, and will walk you through all the advise. They advise what's best for you, because they have to sit there and explain their choices. They can be hard to find, but are generally the best option in my opinion. % of Money These are like the flat rate advisers to me. They get a percentage of the money you give them to \"\"manage\"\". Because they already have your money they are more likely to recommend products that are in their interest. That said, there not all bad. % or Profit These are the best (see notes later). They get a percentage of the money they make for you. They have the most interest in making you money. They only get part of what you get, so there going to make sure you get the biggest pie, so they can get a bigger slice. Notes In the real world, all advisers are likely to get kickbacks on products they recommend. Make sure to keep an eye for that. Also most advisers will use 2-3 of the methods listed above for billing. Something like z% of profit +$x per hour is what I like to see. You will have to look around and see what is available. Just remember that you are paying someone to make you money (or to advise you on how to make money) so long as what they take leaves you with some profit your in a better situation then your are now. And that's the real goal.\"",
"title": ""
},
{
"docid": "47973",
"text": "\"First, I applaud you for caring. Most people don't! In fact, I was in that category. You bring up several issues and I'll try to address them separately. (1) Getting a financial planner to talk with you. I had the same experience! My belief is that they don't want to admit that they don't know how things work. I even asked if I could pay them an hourly fee to ask questions and review stocks with them. Most declined. You'll find that very few people actually take the time to get trained to evaluate stocks and the stock market as a whole. (See later Investools.com). After looking, however, I did find people who would spend an hour or two with me when we met once a quarter to review my \"\"portfolio\"\"/investments. I later found training that companies offered. I would attend any free training I could get because they actually wanted to spend time and talk and teach investors. Bottom line is: Talking to their clients is the job of a financial planner. If he (or she) is not willing to take this time, it is in your best interest to find someone who will spend that time. (2) Learning about investing! I'm not affiliated with anyone. I'm a software developer and I do my own trading/investments. The opinions I share are my own. When I was 20 years away from retirement, I started learning about the stock market so that I would know how it worked before I retired so that (a) I could influence a change if one was needed, and (b) so I wouldn't have to blindly accept the advice of the \"\"experts\"\" even when the stock market is crashing. I have used Investools.com, and TDAmeritrade's Think-or-Swim platform. I've learned a tremendous amount from the Investools training. I recommend them. But don't expect to learn how to get rich from them or any training you take. The TDA Think-or-swim platform I highly recommend BECAUSE it has a feature called \"\"Paper Money\"\". It lets you trade using the real market but with play money. I highly recommend ANY platform that you can use to trade IN PAPER money! The think-or-swim platform would allow you to invest $30,000 in paper money (you can have as much as you want) into any stock. This would let you see if you can make more money than your current investment advisor. You could invest $10K in one SPY, $10K in DIA and $10K in IWM (these are symbols for the S&P 500, Dow 30, and Small Cap stocks). This is just an example, I'm not suggesting any investment advise! It's important that you actually do this not just write down on a piece of paper or Excel spreadsheet what you were going to do because it's common to \"\"cheat\"\" and change the dates to meet your needs. I have found it incredibly helpful to understand how the market works by trying to do my own paper and now real money investing. I was and you will be surprised to find that many trades lose money during the initial start part of the trade because it's very difficult to buy at the exact right time. An important part of managing your own investments is learning to trade with rules and not get \"\"emotionally involved\"\" in your trades. (3) Return on investment. You were not happy with $12 return. Low returns are a byproduct of the way most investment firms (financial planners) take (diversification). They diversify to take a \"\"hands off\"\" approach toward investment because that approach has been the only approach that they have found that works relatively well in all market conditions. It's not (necessarily) a bad approach. It avoids large losses in down markets (most riskier approaches lose more than the market). The downside is it also avoids the high returns. If the market goes up 15% the investment might only go up 5%. 30K is enough to give to multiple investment firms a try. I gave two different firms $25K each to see how they would invest. The direction was to accept LOTS of risk (with the potential for large losses or large gains). In a year that the market did very well, one lost money, and one made a small gain. It was a learning experience. I, now, have taken the money back and invest it myself. NOTE: I would be happy with a guy who made me 10-15% year over year (in good times and bad) and didn't talk with me, but I haven't found someone who can do that. :-) NOTE 2: Don't believe what you hear from the news about the stock market being up 5% year to date. Do your own analysis. NOTE 3: Investing in \"\"the market\"\" (S&P 500 for example) is a great way to go if you're just starting. Few investment firms can beat \"\"the market\"\" although many try to do so. I too have found it's easier to do that than other approaches I've learned. So, it might be a good long term approach as well. Best wishes to you in your learning about the market and desires to make money with your money. That is what is all about.\"",
"title": ""
}
] |
6299
|
What should a 19 year old with a moderate inheritance look for in a financial advisor?
|
[
{
"docid": "551849",
"text": "\"I think your question is pretty wise, and the comments indicate that you understand the magnitude of the situation. First off, there could be nothing that your friend could do. Step parent relationships can be strained and this could make it worse, add the age of the girl and grief and he could make this a lot worse then it potentially is. She may spend it all to spite step-dad. Secondly, there is a need to understand by all involved that personal finance is about 75-90% behavior. Very high income people can wind up bankrupt, and lower income people can end up wealthy. The difference between two people's success or failure often boils down to behavior. Thirdly, I think you understand that there needs to be a \"\"why\"\", not only a \"\"what\"\" to do. I think that is the real tricky part. There has to be a teaching component along with an okay this is what you should do. Finding a person will be difficult. First off there is not a lot of money involved. Good financial advisers handle much larger cash positions and this young lady will probably need to spend some of it down. Secondly most FAs are willing to provide a cookie cutter solution to the problem at hand. This will likely leave a bad taste in the daughter's mouth. If it was me, I would encourage two things: Both of those things buy time. If she comes out of this with an education in a career field with a 50-60K starting salary, a nice used car, and no student loans that would be okay. I would venture to say mom would be happy. If she is very savvy, she might be able to come out of this with a down payment on a place of her own; or, if she has education all locked up perhaps purchasing a home for mostly cash. In the interim period a search for a good teaching FA could occur. Finding such a person could also help you and your friend in addition to the daughter. Now my own step-daughter and I have a good financial relationship. There are other areas where our relationship can be strained but as far as finances we relate well. We took Financial Peace University ($100 offered through many local churches) together when she was at the tender age of 16. The story of \"\"Ben and Arthur\"\" really spoke to her and we have had many subsequent conversations on the matter. That may work in this case. A youTube video on part of the lesson.\"",
"title": ""
}
] |
[
{
"docid": "500986",
"text": "\"This is always a judgement call based on your own tolerance for risk. Yes, you have a fairly long time horizon and that does mean you can accept more risk/more volatility than someone closer to starting to draw upon those savings, but you're old enough and have enough existing savings that you want to start thinking about reducing the risk a notch. So most folks in your position would not put 100% in stocks, though exactly how much should be moved to bonds is debatable. One traditional rule of thumb for a moderately conservative position is to subtract your age from 100 and keep that percentage of your investments in stock. Websearch for \"\"stock bond age\"\" will find lots of debate about whether and how to modify this rule. I have gone more aggressive myself, and haven't demonstrably hurt myself, but \"\"past results are no guarantee of future performance\"\". A paid financial planning advisor can interview you about your risk tolerance, run some computer models, and recommend a strategy, with some estimate of expected performance and volatility. If you are looking for a semi-rational approach, that may be worth considering, at least as a starting point.\"",
"title": ""
},
{
"docid": "286461",
"text": "Yes, there is a profession that does exactly what you're looking for. It's called a fee-only financial advisor. These are professionals who (in the United States) enter into a fiduciary relationship with a client, meaning they are legally required to put your financial interests above all other considerations (such as any behind-the-scenes incentives to promote certain products). Between that requirement and the fact that they are paid for their time (and not on commission), they have zero incentive to try to sell you anything that you do not need. Their only job is to help you with your financial situation. (Of course, some of them may be better than others.) See the profession's website here to find such an advisor near you. (Credit to Marketplace Money, the old name for Marketplace Weekend, for mentioning fee-only advisors at least 87 times per show.)",
"title": ""
},
{
"docid": "266481",
"text": "Not sure if you mean that your SO stands to inherit $18 million or has inherited it already. I would hope that her family already has a team of financial advisors at that point. The name of the game at that asset level is protection. You have enough money so you want to keep up with inflation and generate some income. Most of my firm's clients at that size have at least 50% in tax-free municipal bonds the other half is about 10% in aggressive investments (private equity, aggressive stock managers), and 25% in conservative stock investments, 5% in international investments, and 10% in alternative investments (long/short, GTAA, hedged equity) . They also tend to have quite a bit of income producing real estate. Make sure you meet with a financial advisory firm the specializes in high net worth clients. I work for an independent RIA so I may be biased towards independent and fee-only firms but it seems like the best arrangement. You pay a percentage of assets under management and get objective investment advice with no commissions. For $18 mil anything over .50% as an advisory fee is a ripoff. You all in investment cost should be less than 0.90%. Also you should look into a high net worth insurance broker. You current insurance salesman will be in way over his head. Feel free to PM me with specific questions. Also, if you want to hire my firm that would be great haha!",
"title": ""
},
{
"docid": "57646",
"text": "You can't actually transfer shares directly unless they were obtained as part of an employee share scheme - see the answers to questions 19 and 20 on this page: http://www.hmrc.gov.uk/isa/faqs.htm#19 Q. Can I put shares from my employee share scheme into my ISA? A. You can transfer any shares you get from into a stocks and shares component of an ISA without having to pay Capital Gains Tax - provided your ISA manager agrees to take them. The value of the shares at the date of transfer counts towards the annual limit. This means you can transfer up to £11,520 worth of shares in the tax year 2013-14 (assuming that you make no other subscriptions to ISAs, in those years). You must transfer the shares within 90 days from the day they cease to be subject to the Plan, or (for approved SAYE share option schemes) 90 days of the exercise of option date. Your employer should be able to tell you more. Q. Can I put windfall or inherited shares in my ISA? A. No. You can only transfer shares you own into an ISA if they have come from an employee share scheme. Otherwise, the ISA manager must purchase shares on the open market. The situation is the same if you have shares that you have inherited. You are not able to transfer them into an ISA.",
"title": ""
},
{
"docid": "185443",
"text": "\"First, decide on your asset allocation; are you looking for a fund with 60% stocks/risky-stuff, or 40% or 20%? Second, look for funds that have a mix of stocks and bonds. Good keywords would be: \"\"target retirement,\"\" \"\"lifecycle,\"\" \"\"balanced,\"\" \"\"conservative/moderate allocation.\"\" As you discover these funds, probably the fund website (but at least Morningstar.com) will tell you the percentage in stocks and risk assets, vs. in conservative bonds. Look for funds that have the percentage you decided on, or as close to it as possible. Third, build a list of funds that meet your allocation goal, and compare the details. Are they based on index funds, or are they actively managed? What is the expense ratio? Is the fund from a reputable company? You could certainly ask more questions here if you have several candidates and aren't sure how to choose. For investing in US dollars one can't-go-wrong choice is Vanguard and they have several suitable funds, but unfortunately if you spend in NIS then you should probably invest in that currency, and I don't know anything about funds in Israel. Update: two other options here. One is a financial advisor who agrees to do rebalancing for you. If you get a cheap one, it could be worth it. Two is that some 401k plans have an automatic rebalancing feature, where you have multiple funds but you can set it up so their computer auto-rebalances you. That's almost as good as having a single fund, though it does still encourage some \"\"mental accounting\"\" so you'd have to try to only look at the total balance, not the individual fund balances, over time. Anyway both of these could be alternatives ways to go on autopilot, besides a single fund.\"",
"title": ""
},
{
"docid": "418652",
"text": "Oh, you were looking for proof? > i got a 19% raise this year. prices aren't up 19% this year. That's a good question you asked there. It's very clear and concise what you were looking for. With your added: > i wasn't looking for an explanation - i was looking for proof, as you provided none. three posts later, it all suddenly becomes so clear. You should be a writer. Just yell at anyone who doesn't get your subtlety and tell them they're wrong.",
"title": ""
},
{
"docid": "404732",
"text": "As a young investor, you should know that the big secret is that profitable long term investing is boring. It is is not buying one day and selling the next and keeping very close tabs on your investments and jumping on the computer and going 'Buy!' , 'Sell'. That makes brokers rich, but not you. So look at investments but not everyday and find something else that's exciting, whether it's dirt biking or WOW or competitive python coding. As a 19 year old, you have a ton of time and you don't need to swing for the fences and make 50% or 30% or even 20% returns every year to do well. And you don't have to pick the best performing stocks, and if you do, you don;t have to buy them at their lowest or sell them at their highest. Go read A Random Walk's guide to Investing by Burton Malkiel and The only Investment Guide you'll ever need by Andrew Tobias. Buy them at used bookstores because it's cheaper that way. And if you want more excitement read You Can Be a Stock Market Genius by Joel GreenBlatt, One up On Wall Street By Peter Lynch, something by Warren Buffet and if you want to be really whacked, read Fooled By Randomness by Nassim Nicholas Talib, But never forget about Tobias and Malkiel, invest a regular amount of money every month from 19 to 65 according to what they write and you'll be a wealthy guy by 65.",
"title": ""
},
{
"docid": "444234",
"text": "You need to find a fiduciary advisor pronto. Yes, you are getting a large amount of money, but you'll probably have to deal with higher than average health expenses and lower earning potential for years to come. You need to make sure the $1.2 million lasts you, and for that you need professional advice, not something you read on the Internet. Finding a knowledgeable advisor who has your interests at heart at a reasonable rate is the key here. These articles are a good start on what to look for: http://www.investopedia.com/articles/financialcareers/08/fiduciary-planner.asp https://www.forbes.com/sites/janetnovack/2013/09/20/6-pointed-questions-to-ask-before-hiring-a-financial-advisor/#2e2b91c489fe http://www.investopedia.com/articles/professionaleducation/11/suitability-fiduciary-standards.asp You should also consider what your earning potential is. You rule out college but at 26, you can have a long productive career and earn way more money than the $1.2 million you are going to get.",
"title": ""
},
{
"docid": "166826",
"text": "\"It's never too early to start estate planning, and if you already have a family, getting your personal affairs in order is a must. The sooner you start planning, the more prepared you will be for life's unexpected twists and turns. The following tips, aimed at those under 40, can help you approach and simplify the estate planning process: Start now, regardless of net worth. [Estate planning](http://money.usnews.com/money/personal-finance/articles/2013/09/19/estate-planning-tips-for-people-under-40) is a crucial process for everyone, regardless of wealth level, says Marc Henn, a certified financial planner and president of Harvest Financial Advisors. \"\"Many people will say, 'Well, I don't have a lot of assets, therefore I don't need an estate plan,'\"\" he says. \"\"Maybe you only have debt, but it still applies. If you want the people around you to appropriately deal with your finances, a plan is still just as important.\"\" This is especially true if you are responsible for financially dependent individuals, such as young children. \"\"The less you have, the more important every bit you've got is to you and the people you care about,\"\" says Lawrence Lehmann, a partner at Lehmann, Norman and Marcus L.C. in New Orleans. \"\"If you don't have much money, you really can't afford to make a mistake.\"\" Have the \"\"what if?\"\" conversation with friends and family. Before jumping into the estate planning process, it's important to establish exactly what you want, and need, to happen after you die and relay those wishes to those around you. \"\"We find that the best transitions and financial transfers happen when all family members are involved in the [decision making](http://corlisslawgroup.com),\"\" says John Sweeney, executive vice president of retirement and investing strategies at Fidelity Investments. \"\"This way, after a loved one is gone, no one is squabbling over a couch or going, 'Why did person A get more than person B?' If wishes are laid out clearly while the individual is living, they can share the rationale behind the decisions.\"\" Focus on the basic estate plan components. Experts say life insurance, a will, a living will and a durable power of attorney are all important aspects of an estate plan that should be established at the start of the planning process. In the event of an untimely death, life insurance can replace lost earnings, which can be especially beneficial for younger individuals, says Bill Kirchick, a partner with Bingham McCutchen law firm in Boston. \"\"Young people can't afford to die,\"\" he says. \"\"They are going to lose a source of income if something happens to a young couple and they haven't had enough time to accumulate wealth from earnings to put aside in savings or a retirement plan.\"\" Also, the earlier you take out a life insurance policy, the more likely you are to be approved for reduced rates compared to older individuals. Utilize estate planning professionals. To draft these basic estate plans, experts recommend carefully selecting a team of professionals who will educate you and draft what you need based on your individual situation. \"\"Don't feel like you have to jump at the first person whose name is given to you,\"\" Kirchick says. \"\"I think that people should interview two or more attorneys, accountants, trust officers, financial advisors and so on.\"\" According to financial planning experts, the average initial cost for the legal drafting of a will, living will and durable power of attorney documentation is between $500 and $1,200, depending on the family size and location. Continue to review your plan over time. Finally, your estate plan should never be a \"\"one and done thing,\"\" according to Henn. \"\"Every five to seven years, the documents should be readdressed to adapt to significant life events, tax law changes or even the addition of more children,\"\" he says. It is also important to keep tabs on your insurance policies and investments, as they all tie into the estate plan and can fluctuate based on the economic environment. If you have to make revisions, Henn says it will cost as much as it did to create the documents in the first place.\"",
"title": ""
},
{
"docid": "597627",
"text": "\"There is no simple answer to your question. It depends on many things, perhaps most notably what college your daughter ends up going to and what kind of aid you hope to receive. Your daughter will probably fill out the FAFSA as part of her financial aid application. Here is one discussion of what parental assets \"\"count\"\" towards the Expected Family Contribution on the FAFSA. You can find many similar pages by googling. Retirement accounts and primary residence are notable categories that do not count. So, if you were looking to reduce your \"\"apparent\"\" assets for aid purposes, dumping money into your mortgage or retirement account is a possibility. However, you should be cautious when doing this type of gaming, because it's not always clear exactly how it will affect financial aid. For one thing, \"\"financial aid\"\" includes both grants and loans. Everyone wants grants, but sometimes increasing your \"\"eligibility\"\" may just make you (or your daughter) eligible for larger loans, which may not be so great. Also, each college has its own system for allocating financial aid. Individual schools may ask for more detailed information (such as the CSS Profile). So strategies for minimizing your apparent assets that work for one school may not work for others. Some elite schools with large endowments have generous aid policies that allow even families with sizable incomes to pay little or nothing (e.g., Stanford waives tuition for most families with incomes under $125,000). You should probably research the financial aid policies of schools your daughter is interested in. It can be helpful to talk to financial aid advisors at colleges, as well as high school counselors, not to mention general financial advisors if you really want to start getting technical about what assets to move around. Needless to say, it all begins with talking with your daughter about her thoughts on where to go.\"",
"title": ""
},
{
"docid": "98704",
"text": "\"When you hear advice to buy index funds, that usually comes with two additional pieces of investment discipline advice that are important: These two elements are important to give you relative predictability in your outcome 20 years from now. In this old blog post of mine I linked to Warren Buffett talking about this, also mentioned it in a comment on another answer: http://blog.ometer.com/2008/03/27/index-funds/ It's perfectly plausible to do poorly over 20 years if you buy 100% stocks at once, without dollar-cost averaging or rebalancing. It's very very very plausible to do poorly over 10 years, such as the last 10 in fact. Can you really say you know your financial situation in 20-30 years, and for sure won't need that money? Because predictability is important, I like buying a balanced fund and not \"\"pure stocks\"\": http://blog.ometer.com/2010/11/10/take-risks-in-life-for-savings-choose-a-balanced-fund/ (feel a little bad linking to my blog, but retyping all that into this answer seems dumb!) Here's another tip. You can go one step past dollar cost averaging and try value averaging: http://www.amazon.com/Value-Averaging-Strategy-Investment-Classics/dp/0470049774 However, chances are you aren't even going to be good about rebalancing if it's done \"\"by hand,\"\" so personally I would not do value averaging unless you can find either a fund or a financial advisor to do it for you automatically. (Finance Buff blog makes a case for a financial advisor, in case you like that more than my balanced fund suggestion: http://thefinancebuff.com/the-average-investor-should-use-an-investment-advisor-how-to-find-one.html) Like rebalancing, value averaging makes you buy more when you're depressed about the market and less when it's exciting. It's hard. (Dollar cost averaging is easily done by setting up automatic investment, of course, so you don't have to do it manually in the way you would with value averaging.) If you read the usual canonical books on index funds and efficient markets it's easy to remember the takeaway that nobody knows whether the market will go up or down, and yes you won't successfully time the market. But what you can do successfully is use an investment discipline with risk control: assume that the market will fluctuate, that both up and down are likely and possible, and optimize for predictability in light of that. Most importantly, optimize to take your emotions and behavior out of the picture. Some disciplines for example are: there are dozens out there, many of them snake oil, I think these I mentioned are valid. Anyway, you need some form of risk control, and putting all your money in stocks at once doesn't give you a lot of risk control. There's no real need to get creative. A balanced fund that uses index funds for equity and bond portions is a great choice.\"",
"title": ""
},
{
"docid": "504785",
"text": "In such a situation, is it really safe to give financial info to a person who does not encrypt it? Encryption only helps to an extent. i.e. during transmission of data or during brute force makes it more difficult to get the real data. However you concern is more of staff using this data, which encryption will not help much as they would be able to decrypt and see the data. In what ways could it be misused? This depends on the type of data. The financial data can be used to hack into your accounts if other bits of info are known. i.e. most of the times on Telephone requests; say putting card on hold, requesting balance on account, etc; only your address, mother maiden name, last few transaction details are asked. Some critical requests need more ID proofs; so generally not of concern. The other misuse would be selling this to marketing companies, so that you can be bombarded with sales pitch for anything and everything. The PAN and other ID documents are becoming more prone to mis-use. i.e. give a copy of PAN to open fraudulent accounts etc. A good practise would be to mark every copy of ID proof you give with the purpose as to why its given and a date. This would make the ID proof stale to an extent. If she is not going to encrypt it, should I ask her to delete all my old data and then create a new profile for my communication with her; the new profile not being my name, but a fake name? The regulations would not allow her to create fake accounts and may lead to issues and as such any recognised financial advisor would not allow this to be done. Quite a few countries have regulations for financial advisor's that need to be adhered to.",
"title": ""
},
{
"docid": "156253",
"text": "At 19 years old you can and should be investing to see your money grow over the years. Reinvesting the dividends does get to be pretty significant because they compound over many years. Historically this dividend compounding accounts for about half of the total gains from stocks. At 70 years old I am not investing to see my money grow, although that's nice. I am investing to eat. I live on the dividends, and they tend to come in fairly reliably even as the market bounces up and down. For stocks selected with this in mind I get about 4% per year from the dividends.",
"title": ""
},
{
"docid": "595427",
"text": "\"It sounds like the kinds of planners you're talking to might be a poor fit, because they are essentially salespersons selling investments for a commission. Some thoughts on finding a financial planner The good kind of financial planner is going to be able to do a comprehensive plan - look at your whole life, goals, and non-investment issues such as insurance. You should expect to get a document with a Monte Carlo simulation showing your odds of success if you stick to the plan; for investments, you should expect to see a recommended asset allocation and an emphasis on low-cost no-commission (commission is \"\"load\"\") funds. See some of the other questions from past posts, for example What exactly can a financial advisor do for me, and is it worth the money? A good place to start for a planner might be http://napfa.org ; there's also a franchise of planners providing hourly advice called the Garrett Planning Network, I helped my mom hire someone from them and she was very happy, though I do think your results would depend mostly on the individual rather than the franchise. Anyway see http://www.garrettplanningnetwork.com/map.html , they do require planners to be fee-only and working on their CFP credential. You should really look for the Certified Financial Planner (CFP) credential. There are a lot of credentials out there, but many of them mean very little, and others might be hard to get but not mean the right thing. Some other meaningful ones include Chartered Financial Analyst (CFA) which would be a solid investment expert, though not necessarily someone knowledgeable in financial planning generally; and IRS Enrolled Agent, which means someone who knows a lot about taxes. A CPA (accountant) would also be pretty meaningful. A law degree (and estate law know-how) is very relevant to many planning situations, too. Some not-very-meaningful certifications include Certified Mutual Fund Specialist (which isn't bogus, but it's much easier to get than CFP or CFA); Registered Investment Adviser (RIA) which mostly means the person is supposed to understand securities fraud laws, but doesn't mean they know a lot about financial planning. There are some pretty bogus certifications out there, many have \"\"retirement\"\" or \"\"senior\"\" in the name. A good question for any planner is \"\"Are you a fiduciary?\"\" which means are they legally required to act in your interests and not their own. Most sales-oriented advisors are not fiduciaries; they wouldn't charge you a big sales commission if they were, and they are not \"\"on your side\"\" legally speaking. It's a good idea to check with your state regulators or the SEC to confirm that your advisor is registered and ask if they have had any complaints. (Small advisors usually register with the state and larger ones with the federal SEC). If they are registered, they may still be a salesperson who isn't acting in your interests, but at least they are following the law. You can also see if they've been in trouble in the past. When looking for a planner, one firm I found had a professional looking web site and didn't seem sketchy at all, but the state said they were not properly registered and not in compliance. Other ideas A good book is: http://www.amazon.com/Smart-Simple-Financial-Strategies-People/dp/0743269942 it's very approachable and you'd feel more confident talking to someone maybe with more background information. For companies to work with, stick to the ones that are very consumer-friendly and sell no-load funds. Vanguard is probably the one you'll hear about most. But T. Rowe Price, Fidelity, USAA are some other good names. Fidelity is a bit of a mixture, with some cheap consumer-friendly investments and other products that are less so. Avoid companies that are all about charging commission: pretty much anyone selling an annuity is probably bad news. Annuities have some valid uses but mostly they are a bad deal. Not knowing your specific situation in any detail, it's very likely that 60k is not nearly enough, and that making the right investment choices will make only a small difference. You could invest poorly and maybe end up with 50K when you retire, or invest well and maybe end up with 80-90k. But your goal is probably more like a million dollars, or more, and most of that will come from future savings. This is what a planner can help you figure out in detail. It's virtually certain that any planner who is for real, and not a ripoff salesperson, will talk a lot about how much you need to save and so forth, not just about choosing investments. Don't be afraid to pay for a planner. It's well worth it to pay someone a thousand dollars for a really thorough, fiduciary plan with your interests foremost. The \"\"free\"\" planners who get a commission are going to get a whole lot more than a thousand dollars out of you, even though you won't write a check directly. Be sure to convert those mutual fund expense ratios and sales commissions into actual dollar amounts! To summarize: find someone you're paying, not someone getting a commission; look for that CFP credential showing they passed a demanding exam; maybe read a quick and easy book like the one I mentioned just so you know what the advisor is talking about; and don't rush into anything! And btw, I think you ought to be fine with a solid plan. You and your husband have time remaining to work with. Good luck.\"",
"title": ""
},
{
"docid": "275581",
"text": "TL; DR version: What you propose to do might not save you taxes, and may well be illegal. Since you mention your wife, I assume that the Inherited IRA has been inherited from someone other than your spouse; your mother, maybe, who passed away in Fall 2015 as mentioned in your other question (cf. the comment by Ben Miller above)? If so, you must take (at least) the Required Minimum Distribution (RMD) from the Inherited IRA each year and pay taxes on the distribution. What the RMD is depends on how old the Owner of the IRA was when the Owner passed away, but in most cases, it works out to be the RMD for you, the Beneficiary, considered to be a Single Person (see Publication 590b, available on the IRS web site for details). So, Have you taken the (at least) the RMD amount for 2016 from this Inherited IRA? If not, you will owe a 50% penalty of the difference between the amount withdrawn and the RMD amount. No, it is not a typo; the penalty (it is called an excise tax) is indeed 50%. Assuming that the total amount that you have taken as a Distribution from the Inherited IRA during 2016 is the RMD for 2016 plus possibly some extra amount $X, then that amount is included in your taxable income for that year. You cannot rollover any part of the total amount distributed into your own IRA and thereby avoid taxation on the money. Note that it does not matter whether you will be rolling over the money into an existing IRA in your name or will be establishing a new rollover IRA account in your name with the money: the prohibition applies to both ways of handling the matter. If you wish, you can roll over up to $X (the amount over and above the RMD) into a new Inherited IRA account titled exactly the same as the existing Inherited IRA account with a different custodian. If you choose to do so, then the amount that you roll over into the new Inherited IRA account will not included in your taxable income for 2016. To my mind, there is no point to doing such a rollover unless you are unhappy with the current custodian of your Inherited IRA, but the option is included for completeness. Note that the RMD amount cannot be rolled over in this fashion; only the excess over the RMD. If you don't really need to spend the money distributed from your Inherited IRA for your household expenses (your opening statement that your income for 2016 is low might make this unlikely), and (i) you and/or your spouse received compensation (earned income such as wages, salary, self-employment income, commissions for sales, nontaxable combat pay for US Military Personnel, etc) in 2016, and (ii) you were not 70.5 years of age by December 2016, then you and your wife can make contributions to existing IRAs in your names or establish new IRAs in your names. The amount that can be contributed for each IRA is limited to the smaller of $5500 ($6500 for people over 50) and that person's compensation for 2016, but if a joint tax return is filed for 2016, then both can make contributions to their IRAs as long as the sum of the amounts contributed to the IRAs does not exceed the total compensation reported on the joint return. The deadline for making such IRA contributions is the due date for your 2016 Federal income tax return. Since your income for 2016 is less than $98K, you can deduct the entire IRA contribution even if you or your wife are covered by an employer plan such as a 401(k) plan. Thus, your taxable income will be reduced by the IRA contributions (up to a maximum of $11K (or $12 K or $13K depending on ages)) and this can offset the increase in taxable income due to the distribution from the Inherited IRA. Since money is fungible, isn't this last bullet point achieving the same result as rolling over the entire $9.6K (including the RMD) into an IRA in your name, the very thing that the first bullet point above says cannot be done? The answer is that it really isn't the same result and differs from what you wanted to do in several different ways. First, the $9.6K is being put into IRAs for two different people (you and your wife) and not just you alone. Should there, God forbid, be an end to the marriage, that part of your inheritance is gone. Second, you might not even be entitled to make contributions to IRAs (no compensation, or over 70.5 years old in 2016) which would make the whole thing moot. Third, the amount that can be contributed to an IRA is limited to $5500/$6500 for each person. While this does not affect the present case, if the distribution had been $15K instead of $9.6K, not all of that money could be contributed to IRAs for you and your wife. Finally, the contribution to a Traditional IRA might be non-deductible for income tax purposes because the Adjusted Gross Income is too high; once again, not an issue for you for 2016 but something to keep in mind for future years. In contrast, rollovers from one IRA into another IRA (both titled the same) can be in any amount, and they can be done at any time regardless of whether there is compensation for that year or not or what the Adjusted Gross Income is or whether there is coverage by a 401(k) plan. There are no tax consequences to rollovers unless the rollover is from a Traditional IRA to a Roth IRA in which case, the distribution is included in taxable income for that year. What is prohibited is taking the entire amount of the $9.6K distribution from an Inherited IRA and rolling it over into your existing IRA (or establishing a Rollover IRA in your name with that $9.6K); ditto for some money going into your IRA and some into your wife's IRA. I expect that any IRA custodian will likely refuse to allow you to carry out such a rollover transaction but will be glad to accept 2016 contributions (in amounts of up to $5500/$6500) from you into existing IRAs or open a new IRA for you. The custodian will not ask whether you have compensation for 2016 or not (but will check your age!); it is your responsibility to ensure that you do not contribute more than the compensation etc. Incidentally, subject to the $5500/6500 maximum limit, you can (if you choose to do so) contribute the entire amount of your compensation to an IRA, not just the take-home pay amount (which will be smaller than your compensation because of withholding for Social Security and Medicare tax, State and Federal income tax, etc).",
"title": ""
},
{
"docid": "403017",
"text": "\"Most financial \"\"advisors\"\" are actually financial-product salesmen. Their job is to sweet-talk you into parting with as much money as possible - either in management fees, or in commissions (kickbacks) on high-fee investment products** (which come from fees charged to you, inside the investment.) This is a scrappy, cutthroat business for the salesmen themselves. Realistically that is how they feed their family, and I empathize, but I can't afford to buy their product. I wish they would sell something else. These people prey on people's financial lack of knowledge. For instance, you put too much importance on \"\"returns\"\". Why? because the salesman told you that's important. It's not. The market goes up and down, that's normal. The question is how much of your investment is being consumed by fees. How do you tell that (and generally if you're invested well)? You compare your money's performance to an index that's relevant to you. You've heard of the S&P 500, that's an index, relevant to US investors. Take 2015. The S&P 500 was $2058.20 on January 2, 2015. It was $2043.94 on December 31, 2015. So it was flat; it dropped 0.7%. If your US investments dropped 0.7%, you broke even. If you made less, that was lost to the expenses within the investment, or the investment performing worse than the S&P 500 index. I lost 0.8% in 2015, the extra 0.1% being expenses of the investment. Try 2013: S&P 500 was $1402.43 on December 28, 2012 and $1841.10 on Dec. 27, 2013. That's 31.2% growth. That's amazing, but it also means 31.2% is holding even with the market. If your salesman proudly announced that you made 18%... problem! All this to say: when you say the investments performed \"\"poorly\"\", don't go by absolute numbers. Find a suitable index and compare to the index. A lot of markets were down in 2015-16, and that is not your investment's fault. You want to know if were down compared to your index. Because that reflects either a lousy funds manager, or high fees. This may leave you wondering \"\"where can I invest that is safe and has sensible fees? I don't know your market, but here we have \"\"discount brokers\"\" which allow self-selection of investments, charge no custodial fees, and simply charge by the trade (commonly $10). Many mutual funds and ETFs are \"\"index funds\"\" with very low annual fees, 0.20% (1 in 500) or even less. How do you pick investments? Look at any of numerous books, starting with John Bogle's classic \"\"Common Sense on Mutual Funds\"\" book which is the seminal work on the value of keeping fees low. If you need the cool, confident professional to hand-hold you through the process, a fee-only advisor is a true financial advisor who actually acts in your best interest. They honestly recommend what's best for you. But beware: many commission-driven salespeople pretend to be fee-only advisors. The good advisor will be happy to advise investment types, and let you pick the brand (Fidelity vs Vanguard) and buy it in your own discount brokerage account with a password you don't share. Frankly, finance is not that hard. But it's made hard by impossibly complex products that don't need to exist, and are designed to confuse people to conceal hidden fees. Avoid those products. You just don't need them. Now, you really need to take a harder look at what this investment is. Like I say, they make these things unnecessarily complex specifically to make them confusing, and I am confused. Although it doesn't seem like much of a question to me. 1.5% a quarter is 6% a year or 60% in 10 years (to ignore compounding). If the market grows 6% a year on average so growth just pays the fees, they will consume 60% of the $220,000, or $132,000. As far as the $60,000, for that kind of money it's definitely worth talking to a good lawyer because it sounds like they misrepresented something to get your friend to sign up in the first place. Put some legal pressure on them, that $60k penalty might get a lot smaller. ** For instance they'll recommend JAMCX, which has a 5.25% buy-in fee (front-end load) and a 1.23% per year fee (expense ratio). Compare to VIMSX with zero load and a 0.20% fee. That front-end load is kicked back to your broker as commission, so he literally can't recommend VIMSX - there's no commission! His company would, and should, fire him for doing so.\"",
"title": ""
},
{
"docid": "17633",
"text": "There can be Federal estate tax as well as State estate tax due on an estate, but it is not of direct concern to you. Estate taxes are paid by the estate of the decedent, not by the beneficiaries, and so you do not owe any estate tax. As a matter of fact, most estates in the US do not pay Federal estate tax at all because only the amount that exceeds the Federal exemption ($5.5M) is taxable, and most estates are smaller. State estate taxes might be a different matter because while many states exempt exactly what the Federal Government does, others exempt different (usually smaller) amounts. But in any case, estate taxes are not of concern to you except insofar as what you inherit is reduced because the estate had to pay estate tax before distributing the inheritances. As JoeTaxpayer's answer says more succinctly, what you inherit is net of estate tax, if any. What you receive as an inheritance is not taxable income to you either. If you receive stock shares or other property, your basis is the value of the property when you inherit it. Thus, if you sell at a later time, you will have to pay taxes only on the increase in the value of the property from the time you inherit it. The increase in value from the time the decedent acquired the property till the date of death is not taxable income to you. Exceptions to all these favorable rules to you is the treatment of Traditional IRAs, 401ks, pension plans etc that you inherit that contain money on which the decedent never paid income tax. Distributions from such inherited accounts are (mostly) taxable income to you; any part of post-tax money such as nondeductible contributions to Traditional IRAs that is included in the distribution is tax-free. Annuities present another source of complications. For annuities within IRAs, even the IRS throws up its hands at explaining things to mere mortals who are foolhardy enough to delve into Pub 950, saying in effect, talk to your tax advisor. For other annuities, questions arise such as is this a tax-deferred annuity and whether it was purchased with pre-tax money or with post-tax money, etc. One thing that you should check out is whether it is beneficial to take a lump sum distribution or just collect the money as it is distributed in monthly, quarterly, semi-annual, or annual payments. Annuities in particular have heavy surrender charges if they are terminated early and the money taken as a lump sum instead of over time as the insurance company issuing the annuity had planned on happening. So, taking a lump sum would mean more income tax immediately due not just on the lump sum but because the increase in AGI might reduce deductions for medical expenses as well as reduce the overall amount of itemized deductions that can be claimed, increase taxability of social security benefits, etc. You say that you have these angles sussed out, and so I will merely re-iterate Beware the surrender charges.",
"title": ""
},
{
"docid": "591168",
"text": "\"You have a few options: Option #1 - Leave the money where it is If your balance is over $5k - you should be able to leave the money in your former-employer's 401(k). The money will stay there and continue to be invested in the funds that you elect to invest in. You should at the very least be receiving quarterly statements for the account. Even better - you should have access to some type of an online account where you can transfer your investments, rebalance your account, conform to target, etc. If you do not have online account access than I'm sure you can still transfer investments and make trades via a paper form. Just reach out to the 401(k) TPA or Recordkeeper that administers your plan. Their contact info is on the quarterly statements you should be receiving. Option #2 - Rollover the money into your current employer's 401(k) plan. This is the option that I tend to recommend the most. Roll the money over into your current employer's 401(k) plan - this way all the money is in the same place and is invested in the funds that you elect. Let's say you wanted to transfer your investments to a new fund lineup. Right now - you have to fill out the paperwork or go through the online process twice (for both accounts). Moving the money to your current-employer's plan and having all the money in the same place eliminates this redundancy, and allows you to make one simple transfer of all your assets. Option #3 - Roll the money from your former-employer's plan into an IRA. This is a cool option, because now you have a new IRA with a new set of dollar limits. You can roll the money into a separate IRA - and contribute an additional $5,500 (or $6,500 if you are 50+ years of age). So this is cool because it gives you a chance to save even more for retirement. Many IRA companies give you a \"\"sign on bonus\"\" where if you rollover your former-employers 401(k)...they will give you a bonus (typically a few hundred bucks - but hey its free money!). Other things to note: Take a look at your plan document from your former-employer's 401(k) plan. Take a look at the fees. Compare the fees to your current-employer's plan. There could be a chance that the fees from your former-employer's plan are much higher than your current-employer. So this would just be yet another reason to move the money to your current-employer's plan. Don't forget you most likely have a financial advisor that oversees your current-employer's 401(k) plan. This financial advisor also probably takes fees from your account. So use his services! You are probably already paying for it! Talk to your HR at your employer and ask who the investment advisor is. Call the advisor and set up an appointment to talk about your retirement and financial goals. Ask him for his advice - its always nice talking to someone with experience face to face. Good luck with everything!\"",
"title": ""
},
{
"docid": "90153",
"text": "\"You want a fee-only advisor. He charges like an architect or plumber: by the hour or some other \"\"flat fee\"\". That is his only compensation. He is not paid on commission at all. He is not affiliated with any financial services company of any kind. His office is Starbucks. He does not have a well lit office like the commission broker down the street. He does not want you to hand him your money - it stays in the brokerage account of your choice (within reason - some brokerage accounts are terrible and he'll tell you to get out of those). He never asks for the password to your brokerage account. Edit: The UK recently outlawed commission brokers. These guys were competitive \"\"sales types\"\" who thrive on commissions, and probably went into other sales jobs. So right now, everyone is clamoring for the few proper financial advisors available. High demand is making them expensive. It may not be cost-effective to hire an advisor; you may need to learn it yourself. It's not that hard. Ever hear of a plumber who works totally for free, and makes his money selling you wildly overpriced pipe? That's what regular \"\"financial advisors\"\" are. They sell products that are deliberately made unnecessarily complex. The purpose is first, to conceal sales commissions and high internal fees; and second to confuse you, so the financial world feels so daunting that you feel like you need their help just to navigate it. They're trying to fry your brain so you'l just give up and trust them. Products like whole life and variable annuities are only the poster children for how awful all of their financial products are. These products exist to fleece the consumer without quite breaking the law. Of course, everyone goes to see them because they have well lit offices in every town, and they're free and easy to deal with. Don't feel like you need to know everything about finance to invest. You don't need to understand every complex financial product that the brokerage houses bave dreamed up: they are designed to conceal and confuse, as I discuss above, and you don't want them. The core of it is fairly simple, and that's all you really need to know. Look at any smaller university and how they manage their endowments. If whole life, annuities and those complex financial \"\"products\"\" actually worked, university endowments would be full of them. But they're not! Endowments are generally made of investments you can understand. Partly because university boards are made of investment bankers who invented those products, and know what a ripoff they are. Some people refuse to learn anything. They are done with college and refuse to learn anything more. I hope that's not you. Because you should learn the workings of everything you're investing in. If you don't understand it, don't buy itl And a fee-only financial advisor won't ask you to. 1000 well-heeled, well-advised university endowments seek the most successful products on the market... And end up choosing products you can understand. That's good news for you.\"",
"title": ""
},
{
"docid": "215620",
"text": "The way this works, as I understand it, is that financial advisers come in two kinds. Some are free to recommend you any financial products they think fit, but many are restricted in what they can recommend. Most advisers who work for finance companies are the second kind, and will only offer you products that their company sells. I believe they should tell you up front if they are the second kind. They should certainly tell you that if you ask. So in essence, your Scotiabank advisor is not necessarily making bad decisions for you - but they are restricted in what they will offer, and will not tell you if there is a better product for you that Scotiabank doesn't sell. In most cases, 'management fees' means something you pay to the actual managers of the fund you buy, not to the person who sells you the fund. You can compare the funds you are invested in yourself, both for performance and for the fees charged. Making frequent unnecessary changes of investment is another way that an advisor can milk you for money, but that is not necessarily restricted to bank-employed advisors. if you think that is happening to you, ask question, and change advisors if you are not happy.",
"title": ""
},
{
"docid": "271769",
"text": "Thanks for including a summary for lurkers in your comment. I didn't realize how quickly I was responding, and I did not know you edited. I appreciate you not letting me look ridiculous to browsers. To change course a little bit, I'd like to talk to the idea that if successful people deserve success, unsuccessful people must deserve their lot also. Outside of money, the biggest thing I think we will leave to our kids is what we have learned about money, nutrition, health, and social interaction. Nothing we know is secret knowledge, but at the same time these are fields that are not taught to competence in school, and plenty of hucksters advertise nonsense that make it difficult to quickly learn what makes sense. If you're a 25 year old guy making 35-40k, and you eat at subway because it is endorsed by the American heart association and you assume it's healthy, and you spend 30% of your pre tax income on a house because your mortgage broker said that's normal and your financial advisor said houses are assets, and you buy what you like on credit cards and pay monthly minimums, and you take out an auto lease or a 6 year loan on a purchase to keep payments low, and you diversify what little you have left into mutual funds and bonds, you are doing two things - you are acting like a totally responsible young adult according to societal norms and people who are supposed to give you advice, and you are totally fucking yourself. You are burdening yourself with debt, you aren't investing in yourself, you're neutering your money's ability to help you live a life you actually want to live, and you are shackling yourself to monthly payments that limit your ability to make choices about what you want and how you want to live. Is that your fault? You followed common wisdom and your trusted advisors. Unless you happen to see a different way, or someone comes along and tells you otherwise, you may never know what opportunities you could've had. I'll even concede that having the opportunity to think differently may be luck. But here is where I have a point of contention. What if you've concluded generational wealth is simply luck by the time you have someone try to show you differently? You may dismiss your opportunity as bullshit, and remained trapped in the standard American day to day wage/debt slavery. This is why I hate these semantics so much - I think they rob people of their opportunities.",
"title": ""
},
{
"docid": "132078",
"text": "\"Technically, anyone who advises how you should spend or proportion your money is a financial adviser. A person that does it for money is a Financial Advisor (difference in spelling). Financial Advisors are people that basically build, manage, or advise on your portfolio. They have a little more institutional knowledge on how/where to invest, given your goals, since they do it on a daily basis. They may know a little more than you since, they deal with many different assets: stocks, ETFs, mutual funds, bonds, insurances (home/health/life), REITs, options, futures, LEAPS, etc. There is risk in everything you do, which is why what they propose is generally according to the risk-level you want to assume. Since you're younger, your risk level could be a little higher, as you approach retirement, your risk level will be lower. Risk level should be associated with how likely you're able to reacquire your assets if you lose it all as well as, your likelihood to enjoy the fruits from your investments. Financial Advisors are great, however, be careful about them. Some are payed on commissions, which are given money for investing in packages that they support. Basically, they could get paid $$ for putting you in a losing situation. Also be careful because some announce that they are fee-based - these advisers often receive fees as well as commissions. Basically, associate the term \"\"commission\"\" with \"\"conflict-of-interest\"\", so you want a fee-only Advisor, which isn't persuaded to steer you wrong. Another thing worth noting is that some trading companies (like e*trade) has financial services that may be free, depending how much money you have with them. Generally, $50K is on the lower end to get a Financial Advisors. There has been corruption in the past, where Financial Advisors are only given a limited number of accounts to manage, that means they took the lower-valued ones and basically ran them into the ground, so they could get newer ones from the lot that were hopefully worth more - the larger their portfolio, the more $$ they could make (higher fees or more commissions) and subjectively less work (less accounts to have to deal with), that's subjective, since the spread of the wealth was accross many markets.\"",
"title": ""
},
{
"docid": "248368",
"text": "I'd advise you to look for an advisor who is a NAPFA-Registered Financial Advisor. If you visit the National Association of Personal Financial Advisors (NAPFA) website (http://www.napfa.org) and understand why they are different, I think you'll agree that the NAPFA-Registered Financial Advisor is the highest standard of excellence you will find in a financial planner.",
"title": ""
},
{
"docid": "134037",
"text": "\"I know your \"\"pain\"\". But don't worry about investing the money right now -- leave it uninvested in the short term. You have other stuff you need to school up on. Investment will come, and it's not that hard. In the short term, focus on taxes. Do some \"\"mock\"\" run-throughs of your expected end-of-year taxes (use last year's forms if this year's aren't available yet). Must you pay estimated tax periodically throughout the year? The tax authorities charge hefty penalties for \"\"forgetting\"\" to do it or \"\"not knowing you have to\"\". Keep an eye out for any other government gotchas. Do not overlook this! This is the best investment you could possibly make. Max out your government sanctioned retirement funds - in the US we have employer plans like 401K or Keogh, and personal plans like the IRA. This is fairly straightforward. Avoid any \"\"products\"\" the financial advisors want to sell you, like annuities. Also if you have the Roth type IRA, learn the difference between that and a normal one. There are some tricks you can do if you expect to have an \"\"off\"\" year in the future. Charitable giving is worth considering at high income levels. Do not donate directly to charities. Instead, use a Donor Advised Fund. It is a charity of its own, which accepts your tax deductible donation, and holds it. You take the tax deduction that year. Then later, when the spirit moves, tell your DAF to donate to the charity of your choice. This eliminates most of the headaches associated with giving. You don't get on the soft-hearted sucker lists, because you tell the DAF not to disclose your address, phone or email. You don't need the charity's acknowledgement letter for your taxes, since your donation was actually to the DAF. It shuts down scams and non-charities, since the DAF confirms their nonprofit status and sends the check to their official address only. (This also bypasses those evil for-profit \"\"fundraising companies\"\".) It's a lot simpler than they want you to know. So-called \"\"financial advisors\"\" are actually salesmen working on commission. They urge you to invest, because that's what they sell. They sell financial products you can't understand because they are intentionally unduly complex, specifically to confuse you. They are trying to psych you into believing all investments are too complex to understand, so you'll give up and \"\"just trust them\"\". Simple investments exist. They actually perform better since they aren't burdened down with overhead and internal complexity. Follow this rule: If you don't understand a financial product, don't buy it. But seriously, do commit and take the time to learn investment. You are the best friend your money will have - or its worst enemy. The only way to protect your money from inflation or financial salesmen is to understand investment yourself. You can have a successful understanding of how to invest from 1 or 2 books. (Certainly not everything; those ingenious salesmen keep making the financial world more complicated, but you don't need any of that junk.) For instance how do you allocate domestic stocks, foreign stocks, bonds, etc. in an IRA if you're under 40? Well... how do smaller universities invest their endowments? They all want the same thing you do. If you look into it, you'll find they all invest about the same. And that's quite similar to the asset mix Suze Orman recommends for young people's IRAs. See? Not that complicated. Then take the time to learn why. It isn't stupid easy, but it is learnable. For someone in your tier of income, I recommend Suze Orman's books. I know that some people don't like her, but that segues into a big problem you'll run into: People have very strong feelings about money. Intense, irrational emotions. People get it from their parents or they get sucked into the \"\"trust trap\"\" I mentioned with so-called financial advisors. They bet their whole savings on whatever they're doing, and their ego is very involved. When they push you toward their salesman or his variable annuity, they want you to agree they invested well. So you kinda have to keep your head low, not listen too much to friends/family, and do your research for yourself. John Bogle's book on mutual funds is a must-read for picking mutual funds and allocating assets. Certain financial advisors are OK. They are \"\"fee only\"\" advisors. They deal with all their customers on a fee-only basis, and are not connected to a company which sells financial products. They will be happy for you to keep your money in your account at your discount brokerage, and do your own trading on asset types (not brands) they recommend. They don't need your password. Here's what not to do: A good friend strongly recommended his financial advisor. In the interview, I said I wanted a fee-only advisor, and he agreed to charge me $2000 flat rate. Later, I figured out he normally works on commissions, because he was selling me the exact same products he'd sell to a commission (free advice) customer, and they were terrible products of course. I fired him fast.\"",
"title": ""
},
{
"docid": "491629",
"text": "\"Others have mentioned the term fiduciary but haven't really gone in to what that is. Despite the name \"\"financial advisor\"\" there is no legal (In the US) mandate as to what that means. Often times a financial advisor is little more than a sales rep whose job it is to sell particular financial instruments. These people will give you good generic advice such as \"\"make sure you have a nest egg\"\" and \"\"don't spend more than you make\"\". However when the rubber hits the road in terms of how to save they will often recommend/insist/pressure a particular asset/security which doesn't necessarily meet your risk/reward preference/tolerance. Often times the assets they pitch have high fees. These people won't charge you for their time because their time is a loss leader for the commissions they make on selling their products. In contrast a fiduciary's job responsibility is to look out for your interests. They shouldn't receive any kind of payment based on what assets you buy. This means that you have to pay them for their time. The NAPFA website seems to have good ideas on choosing an advisor. http://www.napfa.org/HowtoFindAnAdvisor.asp\"",
"title": ""
},
{
"docid": "529324",
"text": "I thought the Finance Buff made a pretty solid argument for a financial advisor the other day: http://thefinancebuff.com/the-average-investor-should-use-an-investment-advisor-how-to-find-one.html But 1.5% is too expensive. The blog post at Finance Buff suggests several alternatives. He also has the great suggestion to use Vanguard's cheap financial planning service if you go with Vanguard. A lot of investing advice fails to consider the human factor. Sure it'd be great to rebalance exactly every 6 months and take precisely the amount of risk to theoretically maximize returns. But, yeah right. It's well-known that in the aggregate individual investors go to cash near market bottoms and then buy near market tops. It's not that they don't know the right thing to do necessarily, it's just that the emotional aspect is stronger than any of us expect. You shouldn't rely on sticking to your investments any more than you rely on sticking to your diet and exercise program ;-) the theoretically optimal solution is not the real-world-people-are-involved optimal solution. My own blog post on this suggests a balanced fund rather than a financial advisor, but I think the right financial advisor could well be a better approach: http://blog.ometer.com/2010/11/10/take-risks-in-life-for-savings-choose-a-balanced-fund/ Anyway, I think people are too quick to think of the main risk as volatility, and to think of investing as simple. Sure in theory it is simple. But the main risk is yourself. Fear at market bottoms, greed at market tops, laziness the rest of the time... so there's potential value in taking yourself out of the picture. The human part is the part that isn't simple. On whether to get a financial advisor in general (not just for investments), see also: What exactly can a financial advisor do for me, and is it worth the money?",
"title": ""
},
{
"docid": "545996",
"text": "What you are positioning as a loan was not a loan at all. Your father bought something to be delivered in the future. Your aunt does not want to deliver it, so she should buy it back at whatever the current market value is. What is the price that your dad believes her share of the inheritance is currently worth? Is that based on actual appraisals and some sort of objective audit? If so, your aunt doesn't have much of a case. If not, then she could seek an audit to bolster her bargaining position. How much did your aunt benefit from having a place to live for the last 15 years. Was that benefit greater than some larger amount of money at an unknown future date? That's probably why she sold her inheritance 15 years ago. Now that the inheritance looks like it is going to be available soon, she wants to trade back after having enjoyed the use of your father's money. That might be okay, but simply paying back the original sum with inflation, but without interest, doesn't seem fair to your father. She may not be able to afford to give any more than what she is offering, in which case, she might want to consider offering the original sum now and some portion of her inheritance as interest on that original sum. I'm not taking sides in this one. If it were one of my siblings, I'd be inclined to give the benefit of the doubt and take a smaller amount back if I felt that the lesson was learned (and if I felt that he/she would make wise use of my gift to him/her). I have no idea what your father's current economic situation is, nor am I aware of any other baggage that might influence his feelings about his sister. It's as likely as not that money isn't really what is bothering him, in which case, the amount she repays may have little to do with bridging the divide between them. You might need to ask different questions in the Interpersonal Skills stack if you want to help your father feel better.",
"title": ""
},
{
"docid": "133935",
"text": "\"I have money to invest. Where should I put it? Anyone who answers with \"\"Give it to me, I'll invest it for you, don't worry.\"\" needs to be avoided. If your financial advisor gives you this line or equivalent, fire him/her and find another. Before you think about where you should put your money, learn about investing. Take courses, read books, consume blogs and videos on investing in stocks, businesses, real estate, and precious metals. Learn what the risks and rewards are for each, and make an informed decision based on what you learned. Find differing opinions on each type of investment and come to your own conclusions for each. I for example, do not understand stocks, and so do not seriously work the stock market. Mutual funds make money for the folks selling them whether or not the price goes up or down. You assume all the risk while the mutual fund advisor gets the reward. If you find a mutual fund advisor who cannot recommend the purchase of a product he doesn't sell, he's not an advisor, he's a salesman. Investing in business requires you either to intimately understand businesses and how to fund them, or to hire someone who can make an objective evaluation for you. Again this requires training. I have no such training, and avoid investing in businesses. Investing in real estate also requires you to know what to look for in a property that produces cash flow or capital gains. I took a course, read some books, gained experience and have a knowledgeable team at my disposal so my wins are greater than my losses. Do not be fooled by people telling you that higher risk means higher reward. Risks that you understand and have a detailed plan to mitigate are not risks. It is possible to have higher reward without increasing risk. Again, do your own research. The richest people in the world do not own mutual funds or IRAs or RRSPs or TFSAs, they do their own research and invest in the things I mentioned above.\"",
"title": ""
},
{
"docid": "76530",
"text": "\"All transactions within an IRA are irrelevant as far as the taxation of the distributions from the IRA are concerned. You can only take cash from an IRA, and a (cash) distribution from a Traditional IRA is taxable as ordinary income (same as interest from a bank, say) without the advantage of any of the special tax rates for long-term capital gains or qualified dividends even if that cash was generated within the IRA from sales of stock etc. In short, just as with what is alleged to occur with respect to Las Vegas, what happens within the IRA stays within the IRA. Note: some IRA custodians are willing to make a distribution of stock or mutual fund shares to you, so that ownership of the 100 shares of GE, say, that you hold within your IRA is transferred to you in your personal (non-IRA) brokerage account. But, as far as the IRS is concerned, your IRA custodian sold the stock as the closing price on the day of the distribution, gave you the cash, and you promptly bought the 100 shares (at the closing price) in your personal brokerage account with the cash that you received from the IRA. It is just that your custodian saved the transaction fees involved in selling 100 shares of GE stock inside the IRA and you saved the transaction fee for buying 100 shares of GE stock in your personal brokerage account. Your basis in the 100 shares of GE stock is the \"\"cash_ that you imputedly received as a distribution from the IRA, so that when you sell the shares at some future time, your capital gains (or losses) will be with respect to this basis. The capital gains that occurred within the IRA when the shares were imputedly sold by your IRA custodian remain within the IRA, and you don't get to pay taxes on that at capital gains rates. That being said, I would like to add to what NathanL told you in his answer. Your mother passed away in 2011 and you are now 60 years old (so 54 or 55 in 2011?). It is likely that your mother was over 70.5 years old when she passed away, and so she likely had started taking Required Minimum Distributions from her IRA before her death. So, You should have been taking RMDs from the Inherited IRA starting with Year 2012. (The RMD for 2011, if not taken already by your mother before she passed away, should have been taken by her estate, and distributed to her heirs in accordance with her will, or, if she died intestate, in accordance with state law and/or probate court directives). There would not have been any 10% penalty tax due on the RMDs taken by you on the grounds that you were not 59.5 years old as yet; that rule applies to owners (your mom in this case) and not to beneficiaries (you in this case). So, have you taken the RMDs for 2012-2016? Or were you waiting to turn 59.5 before taking distributions in the mistaken belief that you would have to pay a 10% penalty for early wthdrawal? The penalty for not taking a RMD is 50% of the amount not distributed; yes, 50%. If you didn't take RMDs from the Inherited IRA for years 2012-2016, I recommend that you consult a CPA with expertise in tax law. Ask the CPA if he/she is an Enrolled Agent with the IRS: Enrolled Agents have to pass an exam administered by the IRS to show that they really understand tax law and are not just blowing smoke, and can represent you in front of the IRS in cases of audit etc,\"",
"title": ""
},
{
"docid": "74402",
"text": "You want CFP or CFA who is also a fiduciary, meaning that by law they have to put your interests ahead of their own. Financial planners who are not fiduciaries can, and often do, recommend investment vehicles that earn them the most commission with little regard of your financial goals. If you already have $500,000 to invest and racking up $100,000 a month you probably qualify for most institutions private client programs. That means that the firm/advisor will look at your financial situation and come up with a custom-tailored investment plan for you which should also include tax planning. I would start with whatever financial institutions you already work with - Schwab, your bank etc. Set up a meeting and see what they have to offer. Make sure you interrogate them about their fees, their licenses/certifications and above all if they are a fiduciary.",
"title": ""
}
] |
251
|
Chenodeoxycholic acid treatment increases brown adipose tissue activity.
|
[
{
"docid": "1568684",
"text": "The interest in brown adipose tissue (BAT) as a target to combat metabolic disease has recently been renewed with the discovery of functional BAT in humans. In rodents, BAT can be activated by bile acids, which activate type 2 iodothyronine deiodinase (D2) in BAT via the G-coupled protein receptor TGR5, resulting in increased oxygen consumption and energy expenditure. Here we examined the effects of oral supplementation of the bile acid chenodeoxycholic acid (CDCA) on human BAT activity. Treatment of 12 healthy female subjects with CDCA for 2 days resulted in increased BAT activity. Whole-body energy expenditure was also increased upon CDCA treatment. In vitro treatment of primary human brown adipocytes derived with CDCA or specific TGR5 agonists increased mitochondrial uncoupling and D2 expression, an effect that was absent in human primary white adipocytes. These findings identify bile acids as a target to activate BAT in humans.",
"title": "The Bile Acid Chenodeoxycholic Acid Increases Human Brown Adipose Tissue Activity."
}
] |
[
{
"docid": "4319174",
"text": "All homeotherms use thermogenesis to maintain their core body temperature, ensuring that cellular functions and physiological processes can continue in cold environments. In the prevailing model of thermogenesis, when the hypothalamus senses cold temperatures it triggers sympathetic discharge, resulting in the release of noradrenaline in brown adipose tissue and white adipose tissue. Acting via the β(3)-adrenergic receptors, noradrenaline induces lipolysis in white adipocytes, whereas it stimulates the expression of thermogenic genes, such as PPAR-γ coactivator 1a (Ppargc1a), uncoupling protein 1 (Ucp1) and acyl-CoA synthetase long-chain family member 1 (Acsl1), in brown adipocytes. However, the precise nature of all the cell types involved in this efferent loop is not well established. Here we report in mice an unexpected requirement for the interleukin-4 (IL-4)-stimulated program of alternative macrophage activation in adaptive thermogenesis. Exposure to cold temperature rapidly promoted alternative activation of adipose tissue macrophages, which secrete catecholamines to induce thermogenic gene expression in brown adipose tissue and lipolysis in white adipose tissue. Absence of alternatively activated macrophages impaired metabolic adaptations to cold, whereas administration of IL-4 increased thermogenic gene expression, fatty acid mobilization and energy expenditure, all in a macrophage-dependent manner. Thus, we have discovered a role for alternatively activated macrophages in the orchestration of an important mammalian stress response, the response to cold.",
"title": "Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis"
},
{
"docid": "14865329",
"text": "Brown fat is a specialized fat depot that can increase energy expenditure and produce heat. After the recent discovery of the presence of active brown fat in human adults and novel transcription factors controlling brown adipocyte differentiation, the field of the study of brown fat has gained great interest and is rapidly growing. Brown fat expansion and/or activation results in increased energy expenditure and a negative energy balance in mice and limits weight gain. Brown fat is also able to utilize blood glucose and lipid and results in improved glucose metabolism and blood lipid independent of weight loss. Prolonged cold exposure and beta adrenergic agonists can induce browning of white adipose tissue. The inducible brown adipocyte, beige adipocyte evolving by thermogenic activation of white adipose tissue have different origin and molecular signature from classical brown adipocytes but share the characteristics of high mitochondria content, UCP1 expression and thermogenic capacity when activated. Increasing browning may also be an efficient way to increase whole brown fat activity. Recent human studies have shown possibilities that findings in mice can be reproduced in human, making brown fat a good candidate organ to treat obesity and its related disorders.",
"title": "Brown Fat and Browning for the Treatment of Obesity and Related Metabolic Disorders"
},
{
"docid": "29691654",
"text": "Until recently, the mechanism of adaptive thermogenesis was ascribed to the expression of uncoupling protein 1 (UCP1) in brown and beige adipocytes. UCP1 is known to catalyze a proton leak of the inner mitochondrial membrane, resulting in uncoupled oxidative metabolism with no production of adenosine triphosphate and increased energy expenditure. Thus increasing brown and beige adipose tissue with augmented UCP1 expression is a viable target for obesity-related disorders. Recent work demonstrates an UCP1-independent pathway to uncouple mitochondrial respiration. A secreted enzyme, PM20D1, enriched in UCP1+ adipocytes, exhibits catalytic and hydrolytic activity to reversibly form N-acyl amino acids. N-acyl amino acids act as endogenous uncouplers of mitochondrial respiration at physiological concentrations. Administration of PM20D1 or its products, N-acyl amino acids, to diet-induced obese mice improves glucose tolerance by increasing energy expenditure. In short-term studies, treated animals exhibit no toxicity while experiencing 10% weight loss primarily of adipose tissue. Further study of this metabolic pathway may identify novel therapies for diabesity, the disease state associated with diabetes and obesity.",
"title": "Uncoupling Mitochondrial Respiration for Diabesity."
},
{
"docid": "29381091",
"text": "Brown adipocytes dissipate energy, whereas white adipocytes are an energy storage site. We explored the plasticity of different white adipose tissue depots in acquiring a brown phenotype by cold exposure. By comparing cold-induced genes in white fat to those enriched in brown compared with white fat, at thermoneutrality we defined a \"brite\" transcription signature. We identified the genes, pathways, and promoter regulatory motifs associated with \"browning,\" as these represent novel targets for understanding this process. For example, neuregulin 4 was more highly expressed in brown adipose tissue and upregulated in white fat upon cold exposure, and cell studies showed that it is a neurite outgrowth-promoting adipokine, indicative of a role in increasing adipose tissue innervation in response to cold. A cell culture system that allows us to reproduce the differential properties of the discrete adipose depots was developed to study depot-specific differences at an in vitro level. The key transcriptional events underpinning white adipose tissue to brown transition are important, as they represent an attractive proposition to overcome the detrimental effects associated with metabolic disorders, including obesity and type 2 diabetes.",
"title": "Brown and white adipose tissues: intrinsic differences in gene expression and response to cold exposure in mice"
},
{
"docid": "52865789",
"text": "OBJECTIVE IL-15 is an inflammatory cytokine secreted by many cell types. IL-15 is also produced during physical exercise by skeletal muscle and has been reported to reduce weight gain in mice. Contrarily, our findings on IL-15 knockout (KO) mice indicate that IL-15 promotes obesity. The aim of this study is to investigate the mechanisms underlying the pro-obesity role of IL-15 in adipose tissues. METHODS Control and IL-15 KO mice were maintained on high fat diet (HFD) or normal control diet. After 16 weeks, body weight, adipose tissue and skeletal mass, serum lipid levels and gene/protein expression in the adipose tissues were evaluated. The effect of IL-15 on thermogenesis and oxygen consumption was also studied in primary cultures of adipocytes differentiated from mouse preadipocyte and human stem cells. RESULTS Our results show that IL-15 deficiency prevents diet-induced weight gain and accumulation of lipids in visceral and subcutaneous white and brown adipose tissues. Gene expression analysis also revealed elevated expression of genes associated with adaptive thermogenesis in the brown and subcutaneous adipose tissues of IL-15 KO mice. Accordingly, oxygen consumption was increased in the brown adipocytes from IL-15 KO mice. In addition, IL-15 KO mice showed decreased expression of pro-inflammatory mediators in their adipose tissues. CONCLUSIONS Absence of IL-15 results in decreased accumulation of fat in the white adipose tissues and increased lipid utilization via adaptive thermogenesis. IL-15 also promotes inflammation in adipose tissues that could sustain chronic inflammation leading to obesity-associated metabolic syndrome.",
"title": "Deficiency of Interleukin-15 Confers Resistance to Obesity by Diminishing Inflammation and Enhancing the Thermogenic Function of Adipose Tissues"
},
{
"docid": "26902591",
"text": "Cancer-associated cachexia (CAC) is a wasting syndrome characterized by systemic inflammation, body weight loss, atrophy of white adipose tissue (WAT) and skeletal muscle. Limited therapeutic options are available and the underlying mechanisms are poorly defined. Here we show that a phenotypic switch from WAT to brown fat, a phenomenon termed WAT browning, takes place in the initial stages of CAC, before skeletal muscle atrophy. WAT browning is associated with increased expression of uncoupling protein 1 (UCP1), which uncouples mitochondrial respiration toward thermogenesis instead of ATP synthesis, leading to increased lipid mobilization and energy expenditure in cachectic mice. Chronic inflammation and the cytokine interleukin-6 increase UCP1 expression in WAT, and treatments that reduce inflammation or β-adrenergic blockade reduce WAT browning and ameliorate the severity of cachexia. Importantly, UCP1 staining is observed in WAT from CAC patients. Thus, inhibition of WAT browning represents a promising approach to ameliorate cachexia in cancer patients.",
"title": "A switch from white to brown fat increases energy expenditure in cancer-associated cachexia."
},
{
"docid": "38023457",
"text": "Severe quantitative and qualitative brown adipocyte defects are common in obesity. To investigate whether aberrant expression of tumor necrosis factor alpha (TNF-alpha) in obesity is involved in functional brown fat atrophy, we have studied genetically obese (ob/ob) mice with targeted null mutations in the genes encoding the two TNF receptors. The absence of both TNF receptors or p55 receptor alone resulted in a significant reduction in brown adipocyte apoptosis and an increase in beta(3)-adrenoreceptor and uncoupling protein-1 expression in obese mice. Increased numbers of multilocular functionally active brown adipocytes, and improved thermoregulation was also observed in obese animals lacking TNF-alpha function. These results indicate that TNF-alpha plays an important role in multiple aspects of brown adipose tissue biology and mediates the abnormalities that occur at this site in obesity.",
"title": "Tumor necrosis factor alpha mediates apoptosis of brown adipocytes and defective brown adipocyte function in obesity."
},
{
"docid": "2605032",
"text": "We investigated if whether intrauterine protein restriction in combination with overfeeding during lactation would cause adult-onset obesity and metabolic disorders. After birth, litters from dams fed with control (17% protein) and low protein (6% protein) diets were adjusted to a size of four (CO and LO groups, respectively) or eight (CC and LC groups, respectively) pups. All of the offspring were fed a diet containing 12% protein from the time of weaning until they were 90 d old. Compared to the CC and LC groups, the CO and LO groups had higher relative and absolute food intakes, oxygen consumption and carbon dioxide production; lower brown adipose tissue weight and lipid content and greater weight gain and absolute and relative white adipose tissue weight and absolute lipid content. Compared with the CO and CC rats, the LC and LO rats exhibited higher relative food intake, brown adipose tissue weight and lipid content, reduced oxygen consumption, carbon dioxide production and spontaneous activity, increased relative retroperitoneal adipose tissue weight and unaltered absolute white adipose tissue weight and lipid content. The fasting serum glucose was similar among the groups. The area under the glucose curve was higher in the LO and CO rats than in the LC and CC rats. The basal insulinemia and homeostasis model assessment of insulin resistance (HOMA-IR) were lower in the LO group than in the other groups. The total area under the insulin curve for the LO rats was similar to the CC rats, and both were lower than the CO and LC rats. Kitt was higher in the LO, LC and CO groups than in the CC group. Thus, intrauterine protein restriction followed by overfeeding during lactation did not induce obesity, but produced glucose intolerance by impairing pancreatic function in adulthood.",
"title": "Intrauterine protein restriction combined with early postnatal overfeeding was not associated with adult-onset obesity but produced glucose intolerance by pancreatic dysfunction"
},
{
"docid": "40232172",
"text": "The research on mitochondrial functions in adipocytes has increasingly evidenced that mitochondria plays an important role in the onset and/or progression of obesity and related pathologies. Mitochondrial function in brown adipose tissue (BAT) has been classically assessed by measuring either the levels/activity of mitochondrial enzymes, or the respiration in isolated mitochondria. Isolation of mitochondria is not advantageous because it demands significant time and amount of tissue and, as tissue homogenates, disrupts biochemical and physical connections of mitochondria within the cell. Here, we described a new and efficient protocol to analyze the mitochondrial respiratory states in BAT biopsies that relies on intracellular triglyceride depletion followed by tissue permeabilization. In addition to minimizing tissue requirements to ∼17 mg wet weight, the proposed protocol enabled analysis of all mitochondrial respiratory states, including phosphorylation (OXPHOS), no-phosphorylation (LEAK), and uncoupled (ETS) states, as well as the use of substrates for complex I, complex II, and cytochrome c; together, these features demonstrated mitochondrial integrity and validated the preparation efficacy. Therefore, the protocol described here increases the possibilities of answering physiological questions related to small BAT regions of human and animal models, which shall help to unravel the mechanisms that regulate mitochondrial function in health and disease.",
"title": "Triglyceride depletion of brown adipose tissue enables analysis of mitochondrial respiratory function in permeabilized biopsies."
},
{
"docid": "4854076",
"text": "The rising incidence of obesity and associated metabolic diseases has increased the urgency in understanding all aspects of adipose tissue biology. This includes the function of adipocytes, how adipose tissue expands in obesity, and how expanded adipose tissues in adults can impact physiology. Here, we highlight the growing appreciation for the importance of de novo adipocyte differentiation to adipose tissue expansion in adult humans and animals. We detail recent efforts to identify adipose precursor populations that contribute to the physiological postnatal recruitment of white, brown, and beige adipocytes in mice, and summarize new data that reveal the complexity of adipose tissue development in vivo.",
"title": "The expanding problem of adipose depot remodeling and postnatal adipocyte progenitor recruitment."
},
{
"docid": "36838958",
"text": "Uncoupling protein 1 (Ucp1), which is localized in the mitochondrial inner membrane of mammalian brown adipose tissue (BAT), generates heat by uncoupling oxidative phosphorylation. Upon cold exposure or nutritional abundance, sympathetic neurons stimulate BAT to express Ucp1 to induce energy dissipation and thermogenesis. Accordingly, increased Ucp1 expression reduces obesity in mice and is correlated with leanness in humans. Despite this significance, there is currently a limited understanding of how Ucp1 expression is physiologically regulated at the molecular level. Here, we describe the involvement of Sestrin2 and reactive oxygen species (ROS) in regulation of Ucp1 expression. Transgenic overexpression of Sestrin2 in adipose tissues inhibited both basal and cold-induced Ucp1 expression in interscapular BAT, culminating in decreased thermogenesis and increased fat accumulation. Endogenous Sestrin2 is also important for suppressing Ucp1 expression because BAT from Sestrin2(-/-) mice exhibited a highly elevated level of Ucp1 expression. The redox-inactive mutant of Sestrin2 was incapable of regulating Ucp1 expression, suggesting that Sestrin2 inhibits Ucp1 expression primarily through reducing ROS accumulation. Consistently, ROS-suppressing antioxidant chemicals, such as butylated hydroxyanisole and N-acetylcysteine, inhibited cold- or cAMP-induced Ucp1 expression as well. p38 MAPK, a signaling mediator required for cAMP-induced Ucp1 expression, was inhibited by either Sestrin2 overexpression or antioxidant treatments. Taken together, these results suggest that Sestrin2 and antioxidants inhibit Ucp1 expression through suppressing ROS-mediated p38 MAPK activation, implying a critical role of ROS in proper BAT metabolism.",
"title": "Sestrin2 inhibits uncoupling protein 1 expression through suppressing reactive oxygen species."
},
{
"docid": "3621011",
"text": "Proper regulation of energy storage in adipose tissue is crucial for maintaining insulin sensitivity and molecules contributing to this process have not been fully revealed. Here we show that type II transmembrane protein tenomodulin (TNMD) is upregulated in adipose tissue of insulin-resistant versus insulin-sensitive individuals, who were matched for body mass index (BMI). TNMD expression increases in human preadipocytes during differentiation, whereas silencing TNMD blocks adipogenesis. Upon high-fat diet feeding, transgenic mice overexpressing Tnmd develop increased epididymal white adipose tissue (eWAT) mass, and preadipocytes derived from Tnmd transgenic mice display greater proliferation, consistent with elevated adipogenesis. In Tnmd transgenic mice, lipogenic genes are upregulated in eWAT, as is Ucp1 in brown fat, while liver triglyceride accumulation is attenuated. Despite expanded eWAT, transgenic animals display improved systemic insulin sensitivity, decreased collagen deposition and inflammation in eWAT, and increased insulin stimulation of Akt phosphorylation. Our data suggest that TNMD acts as a protective factor in visceral adipose tissue to alleviate insulin resistance in obesity.",
"title": "Tenomodulin promotes human adipocyte differentiation and beneficial visceral adipose tissue expansion."
},
{
"docid": "17973161",
"text": "Uncoupling protein 1 (UCP1) is highly expressed in brown adipose tissue, where it generates heat by uncoupling electron transport from ATP production. UCP1 is also found outside classical brown adipose tissue depots, in adipocytes that are termed 'brite' (brown-in-white) or 'beige'. In humans, the presence of brite or beige (brite/beige) adipocytes is correlated with a lean, metabolically healthy phenotype, but whether a causal relationship exists is not clear. Here we report that human brite/beige adipocyte progenitors proliferate in response to pro-angiogenic factors, in association with expanding capillary networks. Adipocytes formed from these progenitors transform in response to adenylate cyclase activation from being UCP1 negative to being UCP1 positive, which is a defining feature of the beige/brite phenotype, while displaying uncoupled respiration. When implanted into normal chow-fed, or into high-fat diet (HFD)-fed, glucose-intolerant NOD-scid IL2rg(null) (NSG) mice, brite/beige adipocytes activated in vitro enhance systemic glucose tolerance. These adipocytes express neuroendocrine and secreted factors, including the pro-protein convertase PCSK1, which is strongly associated with human obesity. Pro-angiogenic conditions therefore drive the proliferation of human beige/brite adipocyte progenitors, and activated beige/brite adipocytes can affect systemic glucose homeostasis, potentially through a neuroendocrine mechanism.",
"title": "Human ‘brite / beige’ adipocytes develop from capillary networks and their implantation improves metabolic homeostasis in mice"
},
{
"docid": "6227220",
"text": "Despite growing interest and a recent surge in papers, the role of autophagy in glucose and lipid metabolism is unclear. We produced mice with skeletal muscle–specific deletion of Atg7 (encoding autophagy-related 7). Unexpectedly, these mice showed decreased fat mass and were protected from diet-induced obesity and insulin resistance; this phenotype was accompanied by increased fatty acid oxidation and browning of white adipose tissue (WAT) owing to induction of fibroblast growth factor 21 (Fgf21). Mitochondrial dysfunction induced by autophagy deficiency increased Fgf21 expression through induction of Atf4, a master regulator of the integrated stress response. Mitochondrial respiratory chain inhibitors also induced Fgf21 in an Atf4-dependent manner. We also observed induction of Fgf21, resistance to diet-induced obesity and amelioration of insulin resistance in mice with autophagy deficiency in the liver, another insulin target tissue. These findings suggest that autophagy deficiency and subsequent mitochondrial dysfunction promote Fgf21 expression, a hormone we consequently term a 'mitokine', and together these processes promote protection from diet-induced obesity and insulin resistance.",
"title": "Autophagy deficiency leads to protection from obesity and insulin resistance by inducing Fgf21 as a mitokine"
},
{
"docid": "11428884",
"text": "Adipose tissue is an important metabolic organ, the dysfunction of which is associated with the development of obesity, diabetes mellitus, and cardiovascular disease. The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) is considered the master regulator of adipocyte differentiation and function. Although its cell-autonomous role in adipogenesis has been clearly demonstrated in cell culture, previous fat-specific knockouts of the murine PPARγ gene did not demonstrate a dramatic phenotype in vivo. Here, using Adipoq-Cre mice to drive adipose-specific recombination, we report a unique fat-specific PPARγ knockout (PPARγ FKO) mouse model with almost no visible brown and white adipose tissue at age 3 mo. As a consequence, PPARγ FKO mice had hugely enlarged pancreatic islets, massive fatty livers, and dramatically elevated levels of blood glucose and serum insulin accompanied by extreme insulin resistance. PPARγ FKO mice also exhibited delayed hair coat formation associated with absence of dermal fat, disrupted mammary gland development with loss of mammary fat pads, and high bone mass with loss of bone marrow fat, indicating the critical roles of adipose PPARγ in these tissues. Together, our data reveal the necessity of fat PPARγ in adipose formation, whole-body metabolic homeostasis, and normal development of fat-containing tissues.",
"title": "Lipoatrophy and severe metabolic disturbance in mice with fat-specific deletion of PPARγ."
},
{
"docid": "34582256",
"text": "The object of this study was to assess the role of brown adipose tissue (BAT) and the sympathetic nervous system in the rise in heat production associated with endotoxin-induced fever. Oxygen consumption (VO2) was found to be significantly increased (28%) over a 4-h period after two doses of endotoxin (Escherichia coli lipopolysaccharide, 0.3 mg/100 g body wt) given 24 h apart. Injection of a mixed beta-adrenoceptor antagonist (propranolol) reduced VO2 by 14% in endotoxin-treated rats, whereas the selective beta 1- (atenolol) or beta 2- (ICI 118551) antagonists suppressed VO2 by 10%. These drugs did not affect VO2 in control animals. BAT thermogenic activity assessed from measurements of in vitro mitochondrial guanosine 5'-diphosphate (GDP) binding was elevated by 54% in interscapular BAT and by 171% in other BAT depots. Surgical denervation of one lobe of the interscapular depot prevented these responses. Endotoxin failed to stimulate GDP binding in rats fed protein-deficient diets. This may have been because BAT thermogenic activity was already elevated in control rats fed these diets or because endotoxin caused a marked suppression of food intake in the protein-deficient animals. The results indicate that sympathetic activation of BAT is involved in the thermogenic responses to endotoxin and that these can be modified by dietary manipulation.",
"title": "Involvement of sympathetic nervous system and brown fat in endotoxin-induced fever in rats."
},
{
"docid": "25687558",
"text": "The genetically obese (ob/ob) mouse exhibits defective thermoregulatory responses to cold exposure. Pathophysiological explanations for this phenomenon have focused on abnormalities in intracellular metabolism or insensitivity of peripheral tissues to the thermogenic effects of catecholamines. Because the sympathetic nervous system (SNS) is subject to feedback regulation, a peripheral impairment in thermogenesis should be associated with a compensatory increase in SNS activity. To examine SNS activity in the ob/ob mouse, norepinephrine (NE) turnover was measured in heart and interscapular brown adipose tissue (IBAT) of ob/ob and lean mice. The results from studies utilizing radiolabeled NE or inhibition of NE biosynthesis with alpha-methyl-p-tyrosine to measure NE turnover demonstrated reductions in SNS activity of 33-56% in heart and of 45-73% in IBAT in ob/ob mice at ambient temperature (22 degrees C) compared with measurements in lean controls. During cold exposure (4 degrees C) NE turnover increased in heart and IBAT to a similar extent in both ob/ob and lean mice, but NE turnover rates in heart, and probably in IBAT as well, remained lower in the obese mice than in the lean despite the gradual development of hypothermia in the ob/ob mice during this period. Administration of naltrexone, a long-acting opiate antagonist, failed to reverse the suppression of SNS activity observed in the ob/ob mice. These data indicate that diminished SNS activity in ob/ob mice may be an additional factor contributing to the defective thermogenesis characteristic of these animals.",
"title": "Diminished sympathetic nervous system activity in genetically obese (ob/ob) mouse."
},
{
"docid": "20363389",
"text": "In order to elucidate energy balance in the skeletal muscle, we cloned cDNA of a homologue of uncoupling protein (UCP) from rat skeletal muscle. We also cloned rat UCP-2 cDNA from rat brown adipose tissue (BAT). The UCP cloned from rat skeletal muscle showed 57% and 72% identity with rat UCP-1 and UCP-2. The mRNA was expressed abundantly in the skeletal muscle, moderately in the BAT, and slightly in the white adipose tissue (WAT) with a major band at 2.5 kb and a minor band at 2.8 kb, while the UCP-2 gene expression was widely detected in the whole body with substantial levels in the WAT and with slight levels in the skeletal muscle and BAT. The rat UCP cloned in the present study showed 86% identity with the recently cloned human UCP-3, which was also expressed abundantly in the skeletal muscle with a signal of 2.4 kb. Therefore, the rat UCP was considered to be rat UCP-3. In rats fed high-fat diet the UCP-3 gene expression was augmented 2-fold in the skeletal muscle while UCP-2 mRNA levels were increased significantly (1.6-fold) in the epididymal WAT. Augmented expression of UCPs may provide defense against high-fat induced obesity and impairment of glucose metabolism.",
"title": "Cloning of rat uncoupling protein-3 and uncoupling protein-2 cDNAs: their gene expression in rats fed high-fat diet."
},
{
"docid": "1507222",
"text": "Weight loss in cancer cachexia is attributable to decreased food intake and/or enhanced energy expenditure. We investigated the roles of the uncoupling proteins (UCPs) UCPI, -2, and -3 in a murine model of cachexia, the MAC16 adenocarcinoma. Weight fell to 24% below that of non-tumor-bearing controls (P < 0.01) 18 days after MAC16 inoculation, with significant reductions in fat-pad mass (-67%; P < 0.01) and muscle mass (-20%; P < 0.01). Food intake was 26-60% lower (P < 0.01) than in controls on days 17-18. Non-tumor-bearing mice, pair-fed to match MAC16-induced hypophagia, showed less weight loss (10% below controls, P < 0.01; 16% above MAC-16, P < 0.01) and smaller decreases in fat-pad mass (21% below controls, P < 0.01). Core temperature in MAC16 mice was significantly lower (-2.4 degrees C, P < 0.01) than in controls, and pair-feeding had no effect. MAC16 mice showed significantly higher UCP1 mRNA levels in brown adipose tissue (BAT) than in controls (+63%, P < 0.01), and pair-feeding had no effect. UCP2 and -3 expression in BAT did not differ significantly between groups. By contrast, UCP2 mRNA levels in skeletal muscle were comparably increased in both MAC16 and pair-fed groups (respectively, 183 and 163% above controls; both, P < 0.05), with no significant difference between these two groups. Similarly, UCP3 mRNA was significantly higher than controls in both MAC16 (+163%, P < 0.05) and pair-fed (+253%, P < 0.01) groups, with no significant difference between the two experimental groups. Overexpression of UCP1 in BAT in MAC16-bearing mice may be an adaptive response to hypothermia, which is apparently induced by tumor products; increased thermogenesis in BAT could increase total energy expenditure and, thus, contribute to tissue wasting. Increased UCP2 and -3 expression in muscle are both attributable to reduced food intake and may be involved in lipid utilization during lipolysis in MAC16-induced cachexia.",
"title": "Increased gene expression of brown fat uncoupling protein (UCP)1 and skeletal muscle UCP2 and UCP3 in MAC16-induced cancer cachexia."
},
{
"docid": "36889513",
"text": "Bile acids regulate the transcription of genes that control cholesterol homeostasis through molecular mechanisms that are poorly understood. Physiological concentrations of free and conjugated chenodeoxycholic acid, lithocholic acid, and deoxycholic acid activated the farnesoid X receptor (FXR; NR1H4), an orphan nuclear receptor. As ligands, these bile acids and their conjugates modulated interaction of FXR with a peptide derived from steroid receptor coactivator 1. These results provide evidence for a nuclear bile acid signaling pathway that may regulate cholesterol homeostasis.",
"title": "Bile acids: natural ligands for an orphan nuclear receptor."
},
{
"docid": "20532591",
"text": "White adipose tissue displays high plasticity. We developed a system for the inducible, permanent labeling of mature adipocytes that we called the AdipoChaser mouse. We monitored adipogenesis during development, high-fat diet (HFD) feeding and cold exposure. During cold-induced 'browning' of subcutaneous fat, most 'beige' adipocytes stem from de novo–differentiated adipocytes. During HFD feeding, epididymal fat initiates adipogenesis after 4 weeks, whereas subcutaneous fat undergoes hypertrophy for a period of up to 12 weeks. Gonadal fat develops postnatally, whereas subcutaneous fat develops between embryonic days 14 and 18. Our results highlight the extensive differences in adipogenic potential in various fat depots.",
"title": "Tracking adipogenesis during white adipose tissue development, expansion and regeneration"
},
{
"docid": "45153864",
"text": "Treatment with second-generation antipsychotic agents such as olanzapine frequently results in metabolic adverse effects, e.g. hyperphagia, weight gain and dyslipidaemia in patients of both genders. The molecular mechanisms underlying metabolic adverse effects are still largely unknown, and studies in rodents represent an important approach in their exploration. However, the validity of the rodent model is hampered by the fact that antipsychotics induce weight gain in female, but not male, rats. When administered orally, the short half-life of olanzapine in rats prevents stable plasma concentrations of the drug. We recently showed that a single intramuscular injection of long-acting olanzapine formulation yields clinically relevant plasma concentrations accompanied by several dysmetabolic features in the female rat. In the current study, we show that depot injections of 100-250 mg/kg olanzapine yielded clinically relevant plasma olanzapine concentrations also in male rats. In spite of transient hyperphagia, however, olanzapine resulted in weight loss rather than weight gain. The resultant negative feed efficiency was accompanied by a slight elevation of thermogenesis markers in brown adipose tissue for the highest olanzapine dose, but the olanzapine-related reduction in weight gain remains to be explained. In spite of the absence of weight gain, an olanzapine dose of 200mg/kg or above induced significantly elevated plasma cholesterol levels and pronounced activation of lipogenic gene expression in the liver. These results confirm that olanzapine stimulates lipogenic effects, independent of weight gain, and raise the possibility that endocrine factors may influence gender specificity of metabolic effects of antipsychotics in the rat.",
"title": "Olanzapine depot exposure in male rats: Dose-dependent lipogenic effects without concomitant weight gain."
},
{
"docid": "970012",
"text": "Molecular mechanisms underlying the cold-associated high cardiovascular risk remain unknown. Here, we show that the cold-triggered food-intake-independent lipolysis significantly increased plasma levels of small low-density lipoprotein (LDL) remnants, leading to accelerated development of atherosclerotic lesions in mice. In two genetic mouse knockout models (apolipoprotein E(-/-) [ApoE(-/-)] and LDL receptor(-/-) [Ldlr(-/-)] mice), persistent cold exposure stimulated atherosclerotic plaque growth by increasing lipid deposition. Furthermore, marked increase of inflammatory cells and plaque-associated microvessels were detected in the cold-acclimated ApoE(-/-) and Ldlr(-/-) mice, leading to plaque instability. Deletion of uncoupling protein 1 (UCP1), a key mitochondrial protein involved in thermogenesis in brown adipose tissue (BAT), in the ApoE(-/-) strain completely protected mice from the cold-induced atherosclerotic lesions. Cold acclimation markedly reduced plasma levels of adiponectin, and systemic delivery of adiponectin protected ApoE(-/-) mice from plaque development. These findings provide mechanistic insights on low-temperature-associated cardiovascular risks.",
"title": "Cold Exposure Promotes Atherosclerotic Plaque Growth and Instability via UCP1-Dependent Lipolysis"
},
{
"docid": "120626",
"text": "Obesity is associated with an increased risk of developing insulin resistance and type 2 diabetes. In obese individuals, adipose tissue releases increased amounts of non-esterified fatty acids, glycerol, hormones, pro-inflammatory cytokines and other factors that are involved in the development of insulin resistance. When insulin resistance is accompanied by dysfunction of pancreatic islet β-cells — the cells that release insulin — failure to control blood glucose levels results. Abnormalities in β-cell function are therefore critical in defining the risk and development of type 2 diabetes. This knowledge is fostering exploration of the molecular and genetic basis of the disease and new approaches to its treatment and prevention.",
"title": "Mechanisms linking obesity to insulin resistance and type 2 diabetes"
},
{
"docid": "10463997",
"text": "Objectives: Autophagy is a highly regulated process that has an important role in the control of a wide range of cellular functions, such as organelle recycling, nutrient availability and tissue differentiation. A recent study has shown an increased autophagic activity in the adipose tissue of obese subjects, and a role for autophagy in obesity-associated insulin resistance was proposed. Body mass reduction is the most efficient approach to tackle insulin resistance in over-weight subjects; however, the impact of weight loss in adipose tissue autophagy is unknown. Subjects:Adipose tissue autophagy was evaluated in mice and humans. Results:First, a mouse model of diet-induced obesity and diabetes was maintained on a 15-day, 40% caloric restriction. At baseline, markers of autophagy were increased in obese mice as compared with lean controls. Upon caloric restriction, autophagy increased in the lean mice, whereas it decreased in the obese mice. The reintroduction of ad libitum feeding was sufficient to rapidly reduce autophagy in the lean mice and increase autophagy in the obese mice. In the second part of the study, autophagy was evaluated in the subcutaneous adipose tissue of nine obese-non-diabetic and six obese-diabetic subjects undergoing bariatric surgery for body mass reduction. Specimens were collected during the surgery and approximately 1 year later. Markers of systemic inflammation, such as tumor necrosis factor-1α, interleukin (IL)-6 and IL-1β were evaluated. As in the mouse model, human obesity was associated with increased autophagy, and body mass reduction led to an attenuation of autophagy in the adipose tissue. Conclusion:Obesity and caloric overfeeding are associated with the defective regulation of autophagy in the adipose tissue. The studies in obese-diabetic subjects undergoing improved metabolic control following calorie restriction suggest that autophagy and inflammation are regulated independently.",
"title": "Defective regulation of adipose tissue autophagy in obesity"
},
{
"docid": "12658073",
"text": "The gut microbiota has been proposed as an environmental factor that affects the development of metabolic and inflammatory diseases in mammals. Recent reports indicate that gut bacteria-derived lipopolysaccharide (LPS) can initiate obesity and insulin resistance in mice; however, the molecular interactions responsible for microbial regulation of host metabolism and mediators of inflammation have not been studied in detail. Hepatic serum amyloid A (SAA) proteins are markers and proposed mediators of inflammation that exhibit increased levels in serum of insulin-resistant mice. Adipose tissue-derived SAA3 displays monocyte chemotactic activity and may play a role in metabolic inflammation associated with obesity and insulin resistance. To investigate a potential mechanistic link between the intestinal microbiota and induction of proinflammatory host factors, we performed molecular analyses of germ-free, conventionally raised and genetically modified Myd88-/- mouse models. SAA3 expression was determined to be significantly augmented in adipose (9.9+/-1.9-fold; P<0.001) and colonic tissue (7.0+/-2.3-fold; P<0.05) by the presence of intestinal microbes. In the colon, we provided evidence that SAA3 is partially regulated through the Toll-like receptor (TLR)/MyD88/NF-kappaB signaling axis. We identified epithelial cells and macrophages as cellular sources of SAA3 in the colon and found that colonic epithelial expression of SAA3 may be part of an NF-kappaB-dependent response to LPS from gut bacteria. In vitro experiments showed that LPS treatments of both epithelial cells and macrophages induced SAA3 expression (27.1+/-2.5-fold vs. 1.6+/-0.1-fold, respectively). Our data suggest that LPS, and potentially other products of the indigenous gut microbiota, might elevate cytokine expression in tissues and thus exacerbate chronic low-grade inflammation observed in obesity.",
"title": "Regulation of Serum Amyloid A3 (SAA3) in Mouse Colonic Epithelium and Adipose Tissue by the Intestinal Microbiota"
},
{
"docid": "31564409",
"text": "Objectives:The orexigenic hormone ghrelin circulates mainly in two forms, acylated and desacyl ghrelin. We evaluated the impact of obesity and obesity-associated type 2 diabetes (T2D) on ghrelin forms and the potential role of acylated and desacyl ghrelin in the control of adipogenesis in humans. Methods:Plasma concentrations of the different ghrelin forms were measured in 80 subjects. The expression of the ghrelin receptor (growth hormone secretagogue receptor, GHS-R) was analyzed in omental adipose tissue using western blot and immunohistochemistry, and the effect of acylated ghrelin and desacyl ghrelin (0.1–1000 pmol l−1) on adipogenesis was determined in vitro in omental adipocytes. Results:Circulating concentrations of acylated ghrelin were increased, whereas desacyl ghrelin levels were decreased, in obesity and obesity-associated T2D. Body mass index, waist circumference, insulin and HOMA (homeostasis model assessment) index were positively correlated with acylated ghrelin levels. Obese individuals showed a lower protein expression of GHS-R in omental adipose tissue. In differentiating omental adipocytes, incubation with both acylated and desacyl ghrelin significantly increased PPARγ (peroxisome proliferator-activated receptor γ) and SREBP1 (sterol-regulatory element binding protein-1) mRNA levels, as well as several fat storage-related proteins, including acetyl-CoA carboxylase, fatty acid synthase, lipoprotein lipase and perilipin. Consequently, both the ghrelin forms stimulated intracytoplasmatic lipid accumulation. Conclusions:Both acylated and desacyl ghrelin stimulate lipid accumulation in human visceral adipocytes. Given the lipogenic effect of acylated ghrelin on visceral adipocytes, the herein-reported elevation of its circulating concentrations in obese individuals may play a role in excessive fat accumulation in obesity.",
"title": "Acylated and desacyl ghrelin stimulate lipid accumulation in human visceral adipocytes"
},
{
"docid": "44614949",
"text": "OBJECTIVE To investigate the role of skeletal muscle (SkM) interleukin (IL)-6 in the regulation of adipose tissue metabolism. METHODS Muscle-specific IL-6 knockout (IL-6 MKO) and IL-6(loxP/loxP) (Floxed) mice were subjected to standard rodent diet (Chow), high-fat diet (HFD), or HFD in combination with exercise training (HFD ExTr) for 16 weeks. RESULTS Total fat mass increased (P < 0.05) in both genotypes with HFD. However, HFD IL-6 MKO mice had lower (P < 0.05) inguinal adipose tissue (iWAT) mass than HFD Floxed mice. Accordingly, iWAT glucose transporter 4 (GLUT4) protein content, 5'AMP activated protein kinase (AMPK)(Thr172) phosphorylation, and fatty acid synthase (FAS) mRNA content were lower (P < 0.05) in IL-6 MKO than Floxed mice on Chow. In addition, iWAT AMPK(Thr172) and hormone-sensitive lipase (HSL)(Ser565) phosphorylation as well as perilipin protein content was higher (P < 0.05) in HFD IL-6 MKO than HFD Floxed mice, and pyruvate dehydrogenase E1α (PDH-E1α) protein content was higher (P < 0.05) in HFD ExTr IL-6 MKO than HFD ExTr Floxed mice. CONCLUSIONS These findings indicate that SkM IL-6 affects iWAT mass through regulation of glucose uptake capacity as well as lipogenic and lipolytic factors.",
"title": "Skeletal muscle interleukin‐6 regulates metabolic factors in iWAT during HFD and exercise training"
},
{
"docid": "1907601",
"text": "Adipose tissue hypoxia and inflammation have been causally implicated in obesity-induced insulin resistance. Here, we report that, early in the course of high-fat diet (HFD) feeding and obesity, adipocyte respiration becomes uncoupled, leading to increased oxygen consumption and a state of relative adipocyte hypoxia. These events are sufficient to trigger HIF-1α induction, setting off the chronic adipose tissue inflammatory response characteristic of obesity. At the molecular level, these events involve saturated fatty acid stimulation of the adenine nucleotide translocase 2 (ANT2), an inner mitochondrial membrane protein, which leads to the uncoupled respiratory state. Genetic or pharmacologic inhibition of either ANT2 or HIF-1α can prevent or reverse these pathophysiologic events, restoring a state of insulin sensitivity and glucose tolerance. These results reveal the sequential series of events in obesity-induced inflammation and insulin resistance.",
"title": "Increased Adipocyte O2 Consumption Triggers HIF-1α, Causing Inflammation and Insulin Resistance in Obesity"
},
{
"docid": "43192375",
"text": "Adipose tissue macrophages (ATMs) infiltrate adipose tissue during obesity and contribute to insulin resistance. We hypothesized that macrophages migrating to adipose tissue upon high-fat feeding may differ from those that reside there under normal diet conditions. To this end, we found a novel F4/80(+)CD11c(+) population of ATMs in adipose tissue of obese mice that was not seen in lean mice. ATMs from lean mice expressed many genes characteristic of M2 or \"alternatively activated\" macrophages, including Ym1, arginase 1, and Il10. Diet-induced obesity decreased expression of these genes in ATMs while increasing expression of genes such as those encoding TNF-alpha and iNOS that are characteristic of M1 or \"classically activated\" macrophages. Interestingly, ATMs from obese C-C motif chemokine receptor 2-KO (Ccr2-KO) mice express M2 markers at levels similar to those from lean mice. The antiinflammatory cytokine IL-10, which was overexpressed in ATMs from lean mice, protected adipocytes from TNF-alpha-induced insulin resistance. Thus, diet-induced obesity leads to a shift in the activation state of ATMs from an M2-polarized state in lean animals that may protect adipocytes from inflammation to an M1 proinflammatory state that contributes to insulin resistance.",
"title": "Obesity induces a phenotypic switch in adipose tissue macrophage polarization."
}
] |
5954
|
I have made all the payments on a car I cosigned. Do I have to fight for possession of the vehicle?
|
[
{
"docid": "347050",
"text": "Ordinarily a cosigner does not appear on the car's title (thus, no ownership at all in the vehicle), but they are guaranteeing payment of the loan if the primary borrower does not make the payment. You have essentially two options: Stop making payments for him. If he does not make them, the car will be repossessed and the default will appear on both his and your credit. You will have a credit ding to live with, but he will to and he won't have the car. Continue to make payments if he does not, to preserve your credit, and sue him for the money you have paid. In your suit you could request repayment of the money or have him sign over the title (ownership) to you, if you would be happy with either option. I suspect that he will object to both, so the judge is going to have to decide if he finds your case has merit. If you go with option 1 and he picks up the payments so the car isn't repossessed, you can then still take option 2 to recover the money you have paid. Be prepared to provide documentation to the court of the payments you have made (bank statements showing the out-go, or other form of evidence you made the payment - the finance company's statements aren't going to show who made them).",
"title": ""
}
] |
[
{
"docid": "57211",
"text": "\"I am not sure how anyone is answering this unless they know what the loan was for. For instance if it is for a house you can put a lien on the house. If it is for the car in most states you can take over ownership of it. Point being is that you need to go after the asset. If there is no asset you need to go after you \"\"friend\"\". Again we need more specifics to determine the best course of action which could range from you suing and garnishing wages from your friend to going to small claims court. Part of this process is also getting a hold of the lending institution. By letting them know what is going on they may be able to help you - they are good at tracking people down for free. Also the lender may be able to give you options. For example if it is for a car a bank may help you clear this out if you get the car back plus penalty. If a car is not in the red on the loan and it is in good condition the bank turns a profit on the default. If they can recover it for free they will be willing to work with you. I worked in repo when younger and on more than a few occasions we had the cosigner helping. It went down like this... Co-signer gets pissed like you and calls bank, bank works out a plan and tells cosigner to default, cosigner defaults, banks gives cosigner rights to repo vehicle, cosigner helps or actually repos vehicle, bank gets car back, bank inspects car, bank asks cosigner for X amount (sometimes nothing but not usually), cosigner pays X, bank does not hit cosigners credit, bank releases loan and sells car. I am writing this like it is easy but it really requires that asset is still in good condition, that cosigner can get to the asset, and that the \"\"friend\"\" still is around and trusts cosigner. I have seen more than a few cosigners promise to deliver and come up short and couple conspiring with the \"\"friend\"\". I basically think most of the advice you have gotten so far is crap and you haven't provided enough info to give perfect advice. Seeking a lawyer is a joke. Going after a fleeing party could eat up 40-50 billable hours. It isn't like you are suing a business or something. The lawyer could cost as much as repaying the loan - and most lawyers will act like it is a snap of their fingers until they have bled you dry - just really unsound advice. For the most part I would suggest talking to the bank and defaulting but again need 100% of the details. The other part is cosigning the loan. Why the hell would you cosign a loan for a friend? Most parents won't cosign a loan for their own kids. And if you are cosigning a loan, you write up a simple contract and make the non-payment penalties extremely costly for your friend. I have seen simple contracts that include 30% interests rates that were upheld by courts.\"",
"title": ""
},
{
"docid": "247371",
"text": "\"I'm sorry to hear you've made a mistake. Having read the contract of sale we signed, I do not see any remedy to your current situation. However, I'm interested in making sure I do not take advantage of you. As such, I'll return the vehicle, you can return my money plus the bank fees I paid for the cashiers check, tax, title, and registration, and I will look at buying a vehicle from another dealership. This seems to be the most fair resolution. If I were to pay for your mistake at a price I did not agree to, it would not be fair to me. If you were to allow this vehicle to go to me at the price we agreed to, it wouldn't be fair to you. If I were to return the car and begin negotiations again, or find a different car in your lot, it would be difficult for us to know that you were not going to make a similar mistake again. At this point I consider the sale final, but if you'd prefer to have the vehicle back as-is, returning to us the money we gave you as well as the additional costs incurred by the sale, then we will do so in order to set things right. Chances are good you will see them back down. Perhaps they will just cut the additional payment in half, and say, \"\"Well, it's our mistake, so we will eat half the cost,\"\" or similar, but this is merely another way to get you to pay more money. Stand firm. \"\"I appreciate the thought, but I cannot accept that offer. When will you have payment ready so we can return the car?\"\" If you are firm that the only two solutions is to keep the car, or return it for a full refund plus associated costs, I'd guess they'd rather you keep the car - trust me, they still made a profit - but if they decide to have it returned, do so and make sure they pay you in full plus other costs. Bring all your receipts, etc and don't hand over the keys until you have the check in hand. Then go, gladly, to another dealership that doesn't abuse its customers so badly. If you do end up keeping the car, don't plan on going back to that dealership. Use another dealership for warranty work, and find a good mechanic for non-warranty work. Note that this solution isn't legally required in most jurisdictions. Read your contract and all documentation they provided at the time of sale to be sure, but it's unlikely that you are legally required to make another payment for a vehicle after the sale is finalized. Even if they haven't cashed the check, the sale has already been finalized. What this solution does, though, is put you back in the driver's seat in negotiating. Right now they are treating it as though you owe them something, and thus you might feel an obligation toward them. Re-asserting your relationship with them as a customer rather than a debtor is very important regardless of how you proceed. You aren't legally culpable, and so making sure they understand you aren't will ultimately help you. Further, dealerships operate on negotiation. The primary power the customer has in the dealership is the power to walk away from a deal. They've set the situation up as though you no longer have the power to walk away. They didn't threaten with re-possession because they can't - the sale is final. They presented as a one-path situation - you pay. Period. You do have many options, though, and they are very familiar with the \"\"walk away\"\" option. Present that as your chosen option - either they stick with the original deal, or you walk away - and they will have to look at getting another car off the lot (which is often more important than making a profit for a dealership) or selling a slightly used car. If they've correctly pushed the title transfer through (or you, if that's your task in your state) then your brief ownership will show up on carfax and similar reports, and instantly reduces the car's worth. Having the title transfer immediately back to the dealership doesn't look good to future buyers. So the dealership doesn't want the car back. They are just trying to extract more money, and probably illegally, depending on the laws in your jurisdiction. Reassert your position as customer, and decide now that you'll be fine if you have to return it and walk away. Then when you communicate that to them, chances are good they'll simply cave and let the sale stand as-is.\"",
"title": ""
},
{
"docid": "13975",
"text": "\"Imagine that, a car dealership lied to someone trusting. Who would have thought. A big question is how well do you get along with your \"\"ex\"\"? Can you be in the same room without fighting? Can you agree on things that are mutually beneficial? The car will have to be paid off, and taken out of his name. The mechanics on how to do this is a bit tricky and you may want to see a lawyer about it. Having you being the sole owner of the car benefits him because he is no longer a cosigner on a loan. This will help him get additional loans if he chooses, or cosign on his next gf's car. And of course this benefits you as you \"\"own\"\" the car instead of both of you. You will probably have to refinance the car in your name only. Do you have sufficient credit? Once this happens can you pay off the car in like a year or so? If you search this site a similar questions is asked about once per month. Car loans are pretty terrible, in the future you should avoid them. Cosigning is even worse and you should never again participate in such a thing. Another option is to just sell the car and start over with your own car hopefully paid for in cash.\"",
"title": ""
},
{
"docid": "361646",
"text": "\"I'm sorry you are going through this, but what you are dealing with is exactly is how cosigning works. It is among other reasons why you should never cosign a loan for someone unless you are 100% prepared to pay the loan on their behalf. Unfortunately, the main \"\"benefit\"\" to cosigning a loan is to the bank - they don't care who makes payments, only that someone does. It is not in their interest to educate purchasers who can easily get themselves into the situation you are in. What your options are depends a fair bit on the type of loan it is. The biggest problem is that normally as cosigner you cannot force your friend to do anything. If it is for a car, your best bet is to convince them to sell the car and hopefully recoup more than the cost of the loan. Many workplaces have some sort of free service to provide counseling/guidance on this sort of thing. Look into your employee benefits as you may have some free services there. You can sue your friend in small claims court, but keep in mind: It also depends on how big the loan is relative to your income. While it might feel good to sue your friend in small claims court, if it's for $500 it probably isn't worthwhile - but if your friend just stopped paying off their $30k vehicle assuming you will pay for it, even though they can pay for it themselves?\"",
"title": ""
},
{
"docid": "285033",
"text": "\"Here I thought I would not ever answer a question on this site and boom first ten minutes. First and foremost I am in the automotive industry, specifically one of our core competencies is finance department management consulting and the sales process both for the sale of the care as well as the financial transaction. First and foremost new vehicle gross profits are nowhere near 20% for the dealership. In an entry level vehicle like say a Toyota Corolla there is only a few hundreds of dollars in markup from invoice to M.S.R.P. There is also something called holdback that dealers get for achieving certain goals such as sales volume. These are usually pretty easy to hit. As a matter of fact I have never heard of a dealer not getting the hold back on a deal. This hold back is there to cover overhead for the car, the cost of getting it ready to sell, having a lot to park it on, making it ready for delivery, offset some of the cost of sales labor etc. Most dealerships consider the holdback portion of the invoice to not be part of the deal when it comes to negotiations. Certain brands such as KIA and Chrysler have something called \"\"Dealer Cash\"\" these payouts are usually stair stepped according to volume and vary by dealer, location, past history, how the guys at the factory feel that day and any number of combinations. Then there is CSI or Customer Service Index payments, these payments are usually made every 1/4 are on the Parts Statement not the Sales Doc and while they effect the dealers bottom line they almost never affect the sales managers or sales persons payroll so they are not considered a part of the cost of the car. They are however extremely important to the dealer and this is why after you have your new car they want you to bring in your survey for a free oil change or something. IF you are going to give a bad survey they want to throw it away and not send it in, if you are going to give a good survey they want to make sure you fill it out correctly. This is because lets say they ask you on a scale of 1-10 how was your sales person and you put a 9 that is a failing score. Dumb I know but that is how every factory CSI score system I have seen worked. According to NADA the average New Vehicle gross profit including hold back and dealer cash is around $1000.00. No where near 20%. Dealerships would love it if they made 20% on your new F250 Supercrew Diesel at around $50,000.00. One last thing there is something on the invoice called Wholesale Finance Reserve. This is the amount of money the factory forwards to the Dealership to offset the cost of financing vehicle on the floor plan so they can have it for you to look at before you buy. This is usually equal to around 3 months of interest and while you might buy a vehicle that has been on the lot for 2 days they have plenty that have been there much longer so this equals out in a fair to middling run store. General Mangers that know what they are doing can make this really pad their net profit to statement. On to incentives, there are basically 3 kinds. Cash to customer in the form of rebates, Dealer Cash in the form of incentives to dealerships based on volume or the undesirability of a vehicle, and incentive rates or Subvented leases. The rates are pretty self explanatory as they advertised as such (example 0% for 60 Months). Subvented Leased are harder to figure out and usually not disclosed as they are hard to explain and also a source of increased profit. Subvented leases are usually powered by lower cost of money called a money factor (think of it as an interest rate) that is discounted from the lease company or a subsidized residual. Subsidized residuals are virtually verboten on domestic vehicles due to their poor resell values. A subsidized residual works like this, you buy a Toyota Camry and the ALG (automotive lease guide) says it has a residual at 36 months of 48%. Well Toyota Motor Credit says we will give you a subvented residual of 60% basically subsidizing a 2% increase in residual. Since they do not expect to be able to sell the car at auction for that amount they have to set aside the 2% as a future expense. What does this mean to you, it means a lower payment. Also a good rule of thumb if you are told a money factor by your salesperson to figure out what the interest rate is just multiply it by 2400. So if a money factor is give of .00345 you know your actual interest rate is a little bit lower than 8.28% (illustration purposes only money factors are much lower than that right now). So how does this save you money well a lease is basically calculated by multiplying the MSRP by the residual and then subtracting that amount from the \"\"Capitalized Cost\"\" which is the Price paid for the car - trade in + payoff + TT&L-Rebate-Down Payment. That is the depreciation. Then you divide that number by the term of the loan and you have the depreciation amount. So if you have 20K CC and 10K R your D = 10K / 36 = 277 monthly payment. For the rest of the monthly payment you add (I think been a long time since I did this with out a computer) the Residual plus the CC for $30,000 * MF of .00345 = 107 for a total payment of 404 ish. This is not completely accurate but you can use it to make sure a salesperson/finance person is not trying to do one thing and say another as so often happens on leases. 0% how the heck do they make money at that, well its simple. First in 2008 the Fed made all the \"\"Captive\"\" lenders into actual banks instead of whatever they were before. So now they have access to the Fed's discounting window which with todays monetary policies make it almost free money. In the past these lenders had to go through all kinds of hoops to raise funds and securitize loans even for super prime credit. Those days are essentially over. Now they get their short term money just like Bank of America does. Eventually they still bundle these loans and sell them. So in the short term YOU pay for the 0% by giving up part or all of your rebate. This is really important DO NOT GIVE up your rebate for 0% unless it makes sense to do so. When you can get the money at 2.5% and get a $7000.00 rebate (customer cash) on that F250 or 0% take the cash. First of all make the finance guy/gal show you the the difference in total cost they can do do this using the federal truth in lending disclosures on a finance contract. Secondly how long will you keep the vehicle? If you come out ahead by say $1500 by taking the lower rate but you usually trade out every three years this is not going to work. Also and this is important if you are involved in a situation with a total loss like a stolen car or even worse a bad wreck before the breakeven point you lose that price break. Finally on judging what is right for you, just know that future value of the vehicle on for resell or trade-in will take into effect all of these past rebates and value the car accordingly. So if a vehicle depreciates 20% a year for the first 3 years the starting point will essentially be $7000.00 less than you actually paid, using rough numbers. How does this help the dealers and car companies? Well while a dealer struggles to make money on new cars the factory makes all of their money on the new cars and the new car financing. While your individual loan might lose money that money is offset by the loss of rebate and I think Ford does actually pay Ford Motor Credit Company the difference in the rate. The most important thing is what happens later FMCC now has 2500 loans with people with perfect credit. They can now use those loans to budle with people with not so perfect credit that they financed at 12%-18% and buy that money with interest rates in the 2%-3% range. Well that is a hell of a lot of profit. 'How does it help the dealership, well the more super prime credit they have in their portfolio the more subprime credit the banks will buy for them. This means they have more loans originated that are more profitable for them. Say you come in for the 0% but have 590 credit score, they get FMCC to buy the deal because they have a good portfolio and you win because the dealer gets to buy the money at say 9% and sell it to you at say 12% making the spread. You win there because you actually qualified for a rate of around 18% with a subprime company like Santander or Capital One (yes that capital one) so you save a ton on your overall cost of the car. Any dealership that is half way well run makes as much or money in the finance and insurance office than the rest of the dealership. When you factor in what a good F&I Director can do to get deals done with favorable terms that really goes up. Think about that the guys sitting a desk drinking coffee making more than the service department guys all put together. Well that was long winded but there I broke down the car business for whoever read this far.\"",
"title": ""
},
{
"docid": "409647",
"text": "\"I was in a similar situation about a year ago, and the expedient thing to do would be to remove your grandfather from the Title. He would probably have to agree with this, but I think he will if you approach it correctly. In my case, I was the cosigner for my son's car loan and was told by the dealer that I \"\"had to be on the title\"\". This is not true as far as Virginia is concerned (Illinois may be different). I know this because when my son dropped his auto insurance I got the fine for having an uninsured vehicle and was told during the hearing that the dealer was mistaken. It all worked out in the end, but all we had to do was go down to the DMV and get my name taken off of the title. I'm sure if you approach it this way - you do not want him to be responsible for things that you do (who would get sued if you caused an accident?) he would agree to have his name removed from the title.\"",
"title": ""
},
{
"docid": "142876",
"text": "I am 17 and currently have a loan out for a car. My parents also have terrible credit, and because I knew this I was able to get around it. Your co-signer on your loan does not have to be your parent, at least in Wisconsin, I used my grandmother, who has excellent credit, as my cosigner. With my loan, we had made it so it doesn't hurt her credit if I don't get my payments in on time, maybe this is something for you to look into.",
"title": ""
},
{
"docid": "417800",
"text": "\"http://www.nadaguides.com/ and http://www.kbb.com/ and http://www.edmunds.com/ are the leading sites to check vehicle values. Also, great how to at: http://www.ehow.com/how_2003079_sell-used-car-california.html Where to sell? You could sell it in your local newspaper classified, small auto newsprint mags/publications, Craigslist, ebay, or just put a sign in the window. The advertising method is up to you. You could also trade the car in to a dealer if you purchase another vehicle from a dealer if they offer that option. (Trade-In's generally bring in less money than private sales as a general rule). Some car places will do consignment requests to help you sell your car. However, they will normally take a percentage of the sale as payment for this service. What paperwork? If you own your car, you should have the title in hand. There are instructions on title on how to sign it over to another person. If you have a loan through a bank, the bank would have this title and you would need to express your interest in selling the property to the bank and work out the details with them. You do not hand over a title to anyone until full payment is made and the property will become theirs. Beyond the title, you will need to fill out a release of liability or report of sale form for the state. Titles have a portion you can mail in or you can fill it out online. This is to report the sale to the state to release liability from your name. You will also need to create a \"\"bill of sale\"\" between you and the buyer. There are many examples online or you can just create your own. You really need just a statement saying I release all interest of the vehicle and no warranty implied to this person with the VIN of the car, model, make, year, the buyers name and signature, and the sellers name and signature. This is your contract with the seller and they use this when they go to register the car in their name. Maintenance Disclosure? This is completely up to the seller on what they want to disclose. You are selling a used car and the buyer should know that. Vehicles with detailed records sell for more money and buyers are more interested in cars that have history records. This is where buyers should be the most careful, so the more records and history you can show, the better they will feel about the purchase. I believe you should share everything you know and any information about the history of the car. The more positive information you can prove/share, the more money or chance of sale you could have. Most money? First, clean the car out. I am amazed at the amount of people that try to sell a car and don't even bother to clean it out. A detail job would be great to get. You are trying to sell it, so you want it to look the best. Next, I would fix anything minor and cheap to fix. The less things wrong can mean more money. Back to your maintenance question, you will want to show how you have maintained the car. People might also ask for a carfax report to prove its clean history. Irresponsible and deceiving people tend to leave out important details in a car history like accidents, flood damage, or having re-built titles. You want to give the most information you can. Do not lie about any detail. Though, this can be a little tough when you are a 2nd or 3rd owner of a car and do not know about the original owners.\"",
"title": ""
},
{
"docid": "403969",
"text": "\"You promised to pay the loan if he didn't. That was a commitment, and I recommend \"\"owning\"\" your choice and following it through to its conclusion, even if you never do that again. TLDR: You made a mistake: own it, keep your word, and embrace the lesson. Why? Because you keep your promises. (Nevermind that this is a rare time where your answer will be directly recorded, in your credit report.) This isn't moralism. I see this as a \"\"defining moment\"\" in a long game: 10 years down the road I'd like you to be wise, confident and unafraid in financial matters, with a healthy (if distant) relationship with our somewhat corrupt financial system. I know austerity stinks, but having a strong financial life will bring you a lot more money in the long run. Many are leaping to the conclusions that this is an \"\"EX-friend\"\" who did this deliberately. Don't assume this. For instance, it's quite possible your friend sold the (car?) at a dealer, who failed to pay off this note, or did and the lender botched the paperwork. And when the collector called, he told them that, thinking the collector would fix it, which they don't do. The point is, you don't know: your friend may be an innocent party here. Creditors generally don't report late payments to the credit bureaus until they're 30 days late. But as a co-signer, you're in a bad spot: you're liable for the payments, but they don't send you a bill. So when you hear about it, it's already nearly 30 days late. You don't get any extra grace period as a co-signer. So you need to make a payment right away to keep that from going 30 late, or if it's already 30 late, to keep it from going any later. If it is later determined that it was not necessary for you to make those payments, the lender should give them back to you. A less reputable lender may resist, and you may have to threaten small claims court, which is a great expense to them. Cheaper to pay you. They say France is the nation of love. They say America is the nation of commerce. So it's not surprising that here, people are quick to burn a lasting friendship over a temporary financial issue. Just saying, that isn't necessarily the right answer. I don't know about you, but my friends all have warts. Nobody's perfect. Financial issues are just another kind of wart. And financial life in America is hard, because we let commerce run amok. And because our obsession with it makes it a \"\"loaded\"\" issue and thus hard to talk about. Perhaps your friend is in trouble but the actual villain is a predatory lender. Point is, the friendship may be more important than this temporary adversity. The right answer may be to come together and figure out how to make it work. Yes, it's also possible he's a human leech who hops from person to person, charming them into cosigning for him. But to assume that right out of the gate is a bit silly. The first question I'd ask is \"\"where's the car?\"\" (If it's a car). Many lenders, especially those who loan to poor credit risks, put trackers in the car. They can tell you where it is, or at least, where it was last seen when the tracker stopped working. If that is a car dealer's lot, for instance, that would be very informative. Simply reaching out to the lender may get things moving, if there's just a paperwork issue behind this. Many people deal with life troubles by fleeing: they dread picking up the phone, they fearfully throw summons in the trash. This is a terrifying and miserable way to deal with such a situation. They learn nothing, and it's pure suffering. I prefer and recommend the opposite: turn into it, deal with it head-on, get ahead of it. Ask questions, google things, read, become an expert on the thing. Be the one calling the lender, not the other way round. This way it becomes a technical learning experience that's interesting and fun for you, and the lender is dreading your calls instead of the other way 'round. I've been sued. It sucked. But I took it on boldly, and and actually led the fight and strategy (albeit with counsel). And turned it around so he wound up paying my legal bills. HA! With that precious experience, I know exactly what to do... I don't fear being sued, or if absolutely necessary, suing. You might as well get the best financial education. You're paying the tuition!\"",
"title": ""
},
{
"docid": "16606",
"text": "\"Given the state of the economy, and the potential of a rough near future for us recent grads (i.e. on/off work), I would recommend holding off on large purchases while your life is in flux. This includes both a NEW car and purchasing a house. My short answer is: you need a reliable vehicle, so purchase a used car, from a major dealer (yes this will add a fairly high premium, but easier financing), that is 4-5 years old, or more. Barring the major dealer purchase, be sure to get a mechanic to check out a vehicle, many will offer this service for a reasonable payment. As people point out, cars these days will run for another 100k miles. You will NOT have to pay anywhere near $27,000 for this vehicle. You may need to leverage your 10k for a loan if you choose to finance, but it should not be a problem, especially as you seem to imply an established credit history. In addition to this, start saving your money for the house you would like to eventually get. We have no idea where you live, but, picking rough numbers, assuming a 2 year buy period, 20% down, and a $250,000 home, the down payment alone will require you to save ~$2,000/month starting now. Barring either of these options, max out your money to tax sheltered accounts (your Roth IRA, work 401k, or a regular IRA) asap. Obviously, do not deplete your emergency fund, if anything, increase it. 10k can be burned through in a heartbeat. Long Answer: I purchased a brand new car, right out of school, at a reasonable interest rate. Like you, I can afford this vehicle, however, if someone were to come to me today (3.5 years later) and offer me the opportunity to take it back and purchase a 4-5 year used vehicle, at a 4-5 year used car price, albeit at a much higher interest rate (since I financed), it would be about a 0.02 second decision. I like my car, but, I'd like the differential cash savings between it and a reliable used car more. $27,000 is also fairly expensive for a new vehicle, there are many, very nice vehicles, for 21-23k. I still would not consider these priced appropriate to spend your money on them, but they exist. However, you do very much need a reliable vehicle, and I think you should get one. On the home front, your $400 all inclusive rent is insanely cheap. Many people spend more than that on property tax and PMI each year, so anyone who throws the \"\"You're throwing money away!\"\" line at you is blowing smoke to justify their own home purchase. Take the money you would have spent on a mortgage, and squirrel it away. Do your own due diligence and research the home market in your area and decide for yourself if you think home prices have bottomed and will stay there, have further to go, or are going to begin to rise. That is a decision only you can make for yourself. I'd add a section about getting expenses under control, but you said you could save 50% of your takehome pay. This is an order of magnitude above the average. Good job. Try doing 50% for 4 months, then calculate your actual amount. Then try to beat it.\"",
"title": ""
},
{
"docid": "129350",
"text": "There are many reasons for buying new versus used vehicles. Price is not the only factor. This is an individual decision. Although interesting to examine from a macro perspective, each vehicle purchase is made by an individual, weighing many factors that vary in importance by that individual, based upon their specific needs and values. I have purchased both new and used cars, and I have weighted each of these factors as part of each decision (and the relative weightings have varied based upon my individual situation). Read Freakonomics to gain a better understanding of the reasons why you cannot find a good used car. The summary is the imbalance of knowledge between the buyer and seller, and the lack of trust. Although much of economics assumes perfect market information, margin (profit) comes from uncertainty, or an imbalance of knowledge. Buying a used car requires a certain amount of faith in people, and you cannot always trust the trading partner to be honest. Price - The price, or more precisely, the value proposition of the vehicle is a large concern for many of us (larger than we might prefer that it be). Selection - A buyer has the largest selection of vehicles when they shop for a new vehicle. Finding the color, features, and upgrades that you want on your vehicle can be much harder, even impossible, for the used buyer. And once you have found the exact vehicle you want, now you have to determine whether the vehicle has problems, and can be purchased at your price. Preference - A buyer may simply prefer to have a vehicle that looks new, smells new, is clean, and does not have all the imperfections that even a gently used vehicle would exhibit. This may include issues of pride, image, and status, where the buyer may have strong emotional or psychological needs to statisfy through ownership of a particular vehicle with particular features. Reviews - New vehicles have mountains of information available to buyers, who can read about safety and reliability ratings, learn about problems from the trade press, and even price shop and compare between brands and models. Contrasted with the minimal information available to used vehicle shoppers. Unbalanced Knowledge - The seller of a used car has much greater knowledge of the vehicle, and thus much greater power in the negotiation process. Buying a used car is going to cost you more money than the value of the car, unless the seller has poor knowledge of the market. And since many used cars are sold by dealers (who have often taken advantage of the less knowledgeable sellers in their transaction), you are unlikely to purchase the vehicle at a good price. Fear/Risk - Many people want transportation, and buying a used car comes with risk. And that risk includes both the direct cost of repairs, and the inconvenience of both the repair and the loss of work that accompanies problems. Knowing that the car has not been abused, that there are no hidden or lurking problems waiting to leave you stranded is valuable. Placing a price on the risk of a used car is hard, especially for those who only want a reliable vehicle to drive. Placing an estimate on the risk cost of a used car is one area where the seller has a distinct advantage. Warranties - New vehicles come with substantial warranties, and this is another aspect of the Fear/Risk point above. A new vehicle does not have unknown risk associated with the purchase, and also comes with peace of mind through a manufacturer warranty. You can purchase a used car warranty, but they are expensive, and often come with (different) problems. Finance Terms - A buyer can purchase a new vehicle with lower financing rate than a used vehicle. And you get nothing of value from the additional finance charges, so the difference between a new and used car also includes higher finance costs. Own versus Rent - You are assuming that people actually want to 'own' their cars. And I would suggest that people want to 'own' their car until it begins to present problems (repair and maintenance issues), and then they want a new vehicle to replace it. But renting or leasing a vehicle is an even more expensive, and less flexible means to obtain transportation. Expense Allocation - A vehicle is an expense. As the owner of a vehicle, you are willing to pay for that expense, to fill your need for transportation. Paying for the product as you use the product makes sense, and financing is one way to align the payment with the consumption of the product, and to pay for the expense of the vehicle as you enjoy the benefit of the vehicle. Capital Allocation - A buyer may need a vehicle (either to commute to work, school, doctor, or for work or business), but either lack the capital or be unwilling to commit the capital to the vehicle purchase. Vehicle financing is one area banks have been willing to lend, so buying a new vehicle may free capital to use to pay down other debts (credit cards, loans). The buyer may not have savings, but be able to obtain financing to solve that need. Remember, people need transportation. And they are willing to pay to fill their need. But they also have varying needs for all of the above factors, and each of those factors may offer value to different individuals.",
"title": ""
},
{
"docid": "30800",
"text": "I think you are making this more complicated that it has to be. In the end you will end up with a car that you paid X, and is worth Y. Your numbers are a bit hard to follow. Hopefully I got this right. I am no accountant, this is how I would figure the deal: The payments made are irrelevant. The downpayment is irrelevant as it is still a reduction in net worth. Your current car has a asset value of <29,500>. That should make anyone pause a bit. In order to get into this new car you will have to finance the shortfall on the current car (29,500), the price of the vehicle (45,300), the immediate depreciation (say 7,000). In the end you will have a car worth 38K and owe 82K. So you will have a asset value of <44,000>. Obviously a much worse situation. To do this car deal it would cost the person 14,500 of net worth the day the deal was done. As time marched on, it would be more as the reduction in debt is unlikely to keep up with the depreciation. Additionally the new car purchase screen shows a payment of $609/month if you bought the car with zero down. Except you don't have zero down, you have -29,500 down. Making the car payment higher, I estamate 1005/month with 3.5%@84 months. So rather than having a hit to your cash flow of $567 for 69 more months, you would have a payment of about $1000 for 84 months if you could obtain the interest rate of 3.5%. Those are the two things I would focus on is the reduction in net worth and the cash flow liability. I understand you are trying to get a feel for things, but there are two things that make this very unrealistic. The first is financing. It is unlikely that financing could be obtained with this deal and if it could this would be considered a sub-prime loan. However, perhaps a relative could finance the deal. Secondly, there is no way even a moderately financially responsible spouse would approve this deal. That is provided there were not sigificant assets, like a few million. If that is the case why not just write a check?",
"title": ""
},
{
"docid": "541865",
"text": "The general rule is to spend as little as possible on transportation, as it is an expense. Many people can get by without a car at all, but you say you can not. So, what you need is the cheapest car that is sufficiently reliable for your needs. I suggest you do not need three cars. You don't need to loan cars to your children; if they need a car, they can get a job and buy one, or borrow your reliable vehicle if (but only if) you are not using it. I would suggest, then, selling two of your vehicles and holding on to one for your daily commute. Pick the car you judge to be the most reliable. However, not all decisions are made purely rationally. My vehicle is a 2012 Subaru Forester. AWD is very nice in my snowy climate, but I could have picked up a second hand vehicle for a lot less money. Similarly, you may choose to hold on to a second or even a third vehicle because you judge it a reasonable use of your money. It's an unnecessary expense, but so is coffee and you can have my coffee when you pry it from my cold, dead fingers. More generally, there's a rule of 28/36. Roughly speaking, that says that a household should spend a maximum of 28% of its gross income on housing expenses (mortage, heating, etc. etc.), and no more than 36% on total debt (the aforementioned housing, plus also car loans, credit cards, and other loan repayments). If you are spending significantly more than that, it's time to seriously consider selling one or two of your cars, plus cutting back elsewhere. If you are significantly below that, the fact that you may be underwater on your home may be a far less pressing matter.",
"title": ""
},
{
"docid": "85373",
"text": "If you plan to keep this asset for ten years then you can take the deprecation of its cost over that time period. For simplicity lets treat that as 120 monthly payments. So at a purchase price of $60,000 you are committing around $500 per month not including vehicle maintenance. I typically allocate around 20 percent of the purchase price of my vehicles for future maintenance costs. Since you have the cash to purchase this outright you have an option not afforded to most people. This adds for additional consideration. Here is an example. You purchase a $60,000 car and put $10,000 down. You finance $50,000 at 2.84% over 60 months. Your total finance cost is $53,693 if you do not miss any payments. The question here is can you make more than $3,693 on the $50,000 that you would retain in this situation over a five year period? I know that I most certainly can and is an excellent example of why I finance my vehicles. Obviously this all goes out the window if you do not have the credit for top rates. I have also negotiated a vehicle maintenance plan with the dealership at the time of my vehicle purchases. Most dealerships offer this service, the key here is negotiating. On my last truck I was able to get an all inclusive maintenance policy for 72 months for 8% of the purchase price. Your mileage will vary with manufacturer and dealership. As described in the comments above it is never beneficial for an individual to lease. You end up paying more for the newer models. I consider that to be a lifestyle choice as it is most certainly not a sound financial decision.",
"title": ""
},
{
"docid": "323284",
"text": "I don't see how allowing usage of your vehicle is less support than giving money to buy their own vehicle. If that's the only vehicle your mother has - then you're supporting her. Quantifying that support may be difficult though, but if you are providing her all of her needs - it doesn't matter. If she does have income of her own, I do not think that you can put the actual amount you're paying as part of the calculation towards the 50% rule since she would otherwise have bought a much cheaper car. But if you pass the 50% threshold even without the car payments - then you're fine either way.",
"title": ""
},
{
"docid": "338663",
"text": "But.. what I really want to know.... is it illegal, particularly the clause REQUIRING a trade in to qualify for the advertised price? The price is always net of all the parts of the deal. As an example they gave the price if you have $4000 trade in. If you have no trade in, or a trade in worth less than 4K, your final price for the new car will be more. Of course how do you know that the trade in value they are giving you is fair. It could be worth 6K but they are only giving you a credit of 4K. If you are going to trade in a vehicle while buying another vehicle the trade in should be a separate transaction. I always get a price quote for selling the old car before visiting the new car dealer. I do that to have a price point that I can judge while the pressure is on at the dealership.. Buying a car is a complex deal. The price, interest rate, length of loan, and the value of the trade in are all moving parts. It is even more complex if a lease is involved. They want to adjust the parts to be the highest profit that you are willing to agree to, while you think that you are getting a good deal. This is the fine print: All advertised amounts include all Hyundai incentives/rebates, dealer discounts and $2500 additional down from your trade in value. +0% APR for 72 months on select models subject to credit approval through HMF. *No payments or 90 days subject to credit approval. Value will be added to end of loan balance. 15MY Sonata - Price excludes tax, title, license, doc, and dealer fees. MSRP $22085- $2036 Dealer Discount - $500 HMA Lease Cash - $500 HMA Value Owner Coupon - $1000 HMA Retail Bonus Cash - $500 HMA Military Rebate - $500 HMA Competitive Owner Coupon - $400 HMA College Grad Rebate - $500 HMA Boost Program - $4000 Trade Allowance = Net Price $12149. On approved credit. Certain qualifications apply to each rebate. See dealer for details. Payment is 36 month lease with $0 due at signing. No security deposit required. All payment and prices include HMA College Grad Rebate, HMA Military Rebate, HMA Competitive Owner Coupon and HMA Valued Owner Coupon. Must be active military or spouse of same to qualify for HMA Military Rebate. Must graduate college in the next 6 months or within the last 2 years to qualify for HMA College Grad rebate. Must own currently registered Hyundai to qualify for HMA Valued Owner Coupon. Must own qualifying competitive vehicle to qualify for HMA Competitive Owner Coupon.",
"title": ""
},
{
"docid": "322238",
"text": "That totally sucks! I use Avis for work once a year when I'm flown out to corporate and both times I've done so they've managed to fuck up in regards to my reservation. The first time I received an email from them thanking me for using their service when I still had the car and saw a new $300 charge on my credit card. When I called to inquire about the car I had rented 3 days earlier that was still in my possession they informed me that the vehicle had been checked into one of their depots 2300 miles away and they were citing a fee for returning the vehicle to another location. When I asked the agent how many miles were recorded driven on the vehicle she responded with 108. I then asked her how far she thought Chicago was from San Francisco and if it was possible to drive that distance in 3 days while only incurring 108 miles on the vehicle. In the end, they refused to back down and I had to involve corporate to settle everything. The second issue was much less eventful but happened a week ago when I checked out a car. I received an email 2 hours later saying they're sorry my car hadn't been available and to call them for an explanation. Puzzled as I had gotten the car I had asked for I called and was told that their system says I had checked out and in the very same car I had the previous day at 8:34pm (check in and check out were recorded as the same time, same day) and they charged me $50 for a single day's rental. This time they recognized that it was an error and credited me back the money on my CC but I don't know why they have so many issues with their reservation system.",
"title": ""
},
{
"docid": "288701",
"text": "Yes, there are times when co-signing is the right choice. One is when you know more about the person than the loan issuer does. Consider a young person who has just started working in a volatile field, the kind of job where you can be told on Friday that you only get one shift next week but things might pick up the week after, and who makes maybe $12 an hour in that job. You've done the math and with 40 hour weeks they can easily afford the loan. Furthermore, you know this person well and you know that after a few weeks of not enough shifts, they've got the gumption to go out and find a second job or a different job that will give them 40 hours or more a week. And you know that they have some savings they could use to ensure that no payments will be missed even on low-wage weeks. You can cosign for this person, say for a car loan to get them a car they can drive to that job, knowing that they aren't going to walk away and just stop making the payments. The loan issuer doesn't know any of that. Or consider a young person with poor credit but good income who has recently decided to get smart about money, has written out a budget and a plan to rehabilitate their credit, and who you know will work passionately to make every payment and get the credit score up to a place where they can buy a house or whatever their goal is. Again, you can cosign for this person to make that happen, because you know something the lender doesn't. Or consider a middle aged person who's had some very hard knocks: laid off in a plant closing perhaps, marriage failure, lost all their house equity when the market collapsed, that sort of thing. They have a chance to start over again somewhere else and you have a chance to help. Again you know this isn't someone who is going to mismanage their money and walk away from the payments and leave you holding the bag. If you would give the person the money anyway (say, a car for your newly graduated child) then cosigning instead gives them more of a sense of accomplishment, since they paid for it, and gives them a great credit rating too. If you would not give the person the entire loan amount, but would make their payments for many months or even a year (say, your brother's mortgage for the house where he lives with a sick wife and 3 small children), then cosigning is only making official what you would have done anyway. Arrange with the borrower that if they can't make their payments any more, you will backstop them AND the item (car, house, whatever) is going up for sale to cover your losses. If you don't think you could enforce that just from the strength of the relationship, reconsider co-signing. Then sign what you need to sign and step away from it. It's their loan, not yours. You want them to pay it and to manage it and to leave you out of it until it's all paid off and they thank you for your help. If things go south, you will have to pay, and it may take a while for you to sell the item or otherwise stop the paying, so you do need to be very confident that the borrower is going to make every single payment on time. My point is just that you can have that confidence, based on personal knowledge of character, employment situation, savings and other resources, in a way that a lender really cannot.",
"title": ""
},
{
"docid": "190225",
"text": "If you have no credit history but you have a job, buying an inexpensive used car should still be doable with only a marginally higher interest rate on the car. This can be offset with a cosigner, but it probably isn't that big of a deal if you purchase a car that you can pay off in under a year. The cost of insurance for a car is affected by your credit score in many locations, so regardless you should also consider selling your other car rather than maintaining and insuring it while it's not your primary mode of transportation. The main thing to consider is that the terms of the credit will not be advantageous, so you should pay the full balance on any credit cards each month to not incur high interest expenses. A credit card through a credit union is advantageous because you can often negotiate a lower rate after you've established the credit with them for a while (instead of closing the card and opening a new credit card account with a lower rate--this impacts your credit score negatively because the average age of open accounts is a significant part of the score. This advice is about the same except that it will take longer for negative marks like missed payments to be removed from your report, so expect 7 years to fully recover from the bad credit. Again, minimizing how long you have money borrowed for will be the biggest benefit. A note about cosigners: we discourage people from cosigning on other people's loans. It can turn out badly and hurt a relationship. If someone takes that risk and cosigns for you, make every payment on time and show them you appreciate what they have done for you.",
"title": ""
},
{
"docid": "98221",
"text": "\"> In Germany most terror attacks are made by right-wing guys who want to save Germany from the muslim terrorists That's absolutely not true. You know that! Please tell me about the recent right-wing \"\"terror attack\"\" against **civilians** in Germany! Also, how many terror attacks were done by Muslims at the same time against **civilians**? (I am not pro far-right wing people, but they are not the level of Muslims.) **Hey! Did you just say hate speech about right-wing guys? Are they terrorists?** > So the problems comes fron people saying things like you did: Muslims are terrorists. Taking a group as a whole and given them an attribute. If you say americans are fat idiots you say all of them Repeating over and over that if someone says \"\"group X does such and such\"\" means that all members of the group do it will not work. You just said: \"\"*most terror attacks are made by right-wing guys*\"\" and also \"\"*americans are fat idiots*\"\" I say \"\"terrorist attacks are carried out by Muslims\"\" (I did not say \"\"Muslims are terrorists\"\") and the Swedish old lady said \"\"Muslims shit in the street and burn cars\"\". Only the \"\"*americans are fat idiots*\"\" implies that ALL Americans are fat and are also Idiots. Do you understand why? If not, I will explain further. **Do you think I think all Muslims are terrorists?** > heres a link to the sweden Problem No thanks! I don't needs stats from a Swedish source. Here are the stats from a [non-Swedish source](https://en.wikipedia.org/wiki/Crime_in_Sweden): Crime is up a lot. Why? One quote: \"\"**In januray 2017, the the Löfven Cabinet denied the request from member parliament Staffan Danielsson to update the BRÅ statistics on crime with respect to national or immigration background of the perpetrator, as had previously been done in 1995, 2005 but the 2015 was overdue.**\"\" > Your Right about the nazis though. Ignoring isn't helping. Sadly I have other fights to fight ... You have other more important fights? Like to fight \"\"haters\"\" of Muslims? Anyway, my question was: > **As you know, Nazis hate Jews despite Jews being one of the best and most contributing groups in society throughout history. Would you defend Jews being criticized by Nazis? If you do, do you realize what you just did?**\"",
"title": ""
},
{
"docid": "276163",
"text": "\"The lead story here is you owe $12,000 on a car worth $6000!! That is an appalling situation and worth a lot to get out of it. ($6000, or a great deal more if the car is out of warranty and you are at risk of a major repair too.) I'm sorry if it feels like the payments you've made so far are wasted; often the numbers do work out like this, and you did get use of the car for that time period. Now comes an \"\"adversary\"\", who is threatening to snatch the car away from you. I have to imagine they are emotionally motivated. How convenient :) Let them take it. But it's important to fully understand their motivations here. Because financially speaking, the smart play is to manage the situation so they take the car. Preferably unbeknownst that the car is upside down. Whatever their motivation is, give them enough of a fight; keep them wrapped up in emotions while your eye is on the numbers. Let them win the battle; you win the war: make sure the legal details put you in the clear of it. Ideally, do this with consent with the grandfather \"\"in response to his direct family's wishes\"\", but keep up the theater of being really mad about it. Don't tell anyone for 7 years, until the statute of limitations has passed and you can't be sued for it. Eventually they'll figure out they took a $6000 loss taking the car from you, and want to talk with you about that. Stay with blind rage at how they took my car. If they try to explain what \"\"upside down\"\" is, feign ignorance and get even madder, say they're lying and they won, why don't they let it go? If they ask for money, say they're swindling. \"\"You forced me, I didn't have a choice\"\". (which happens to be a good defense. They wanted it so bad; they shoulda done their homework. Since they were coercive it's not your job to disclose, nor your job to even know.) If they want you to take the car back, say \"\"can't, you forced me to buy another and I have to make payments on that one now.\"\"\"",
"title": ""
},
{
"docid": "34722",
"text": "\"This will probably require asking the SO to sign a quitclaim and/or to \"\"sell\"\" him her share of the vehicle's ownership and getting it re-titled in his own name alone, which is the question you actually asked. To cancel the cosigner arrangement, he has to pay off the loan. If he can't or doesn't want to do that in cash, he'd have to qualify for a new loan to refinasnce in his name only, or get someone else (such as yourself) to co-sign. Alternatively, he might sell the car (or something else) to pay what he still owes on it. As noted in other answers, this kind of mess is why you shouldn't get into either cosigning or joint ownership without a written agreement spelling out exactly what happens should one of the parties wish to end this arrangement. Doing business with friends is still doing business.\"",
"title": ""
},
{
"docid": "249017",
"text": "\"Your arrangements with the bank are irrelevant. Whoever is named on the title of the vehicle owns it. If she is the \"\"primary\"\", then I assume her name is on the title, therefore she owns the car. If you drive off with the car and it is titled in her name, she can report it stolen and have you arrested for grand theft auto unless you have a dated and signed permission in writing from her to use the car. Point #2: If a car loan was involved, then you didn't \"\"purchase\"\" the car, the bank did. If you want to gain ownership of the car, then you need to have her name removed from the title and have yours put in its place. Since the bank has possession of the title, this will require the cooperation of both your girlfriend and the bank.\"",
"title": ""
},
{
"docid": "205946",
"text": "Some questions: Will you need a car after 18 months? What are you going to do then? How likely are you able to go over the mileage? Granted paying $300 per month seems somewhat attractive as a fixed cost. However lease are notorious for forcing people into making bad decisions. If your car is over miles, or there is some slight damage (even normal wear and tear), or you customize your car (such as window tint) the dealer can demand extra dollars or force you to purchase the car for more than it is actually worth. The bottom line is leasing is one of the most expensive ways to own a vehicle, and while you have a great income you have a poor net worth. So yes I would say it is somewhat irresponsible for you to own a vehicle. If I was in your shoes, I would cut my gym expenses, cut my retirement contributions to the match, and buy another used car. I understand you may have some burnout over your last car, but it is the best mathematical choice. Having said all that you have a great income and you can absorb a lot of less than efficient decisions. You will probably be okay leasing the car. I would suggest going for a longer term, or cutting something to pay off the student loans earlier. This way there is some cushion between when the lease ends and the student loan ends. This way, when lease turn in comes, you will have some room in your budget to pay some fees as you won't have your student loan payment (assuming around 1400/month) that you can then pay to the dealer.",
"title": ""
},
{
"docid": "162519",
"text": "\"Numbers: Estimate you still owe around 37000 (48500 - 4750, 5% interest, 618 per month payment). Initial price, down payment, payments made - none of these mean anything. Ask your lender, \"\"What is the payoff of the current loan?\"\" Next, sell or trade the current vehicle. Compare to the amount owed. Any shortfall has to be repaid, out of pocket, or in some cases added to the price of the new car and included in the principal of the new loan. You cannot calculate how much you still owe the way you have, because it totally ignores interest. Advice on practicality: Don't do this. You will be upside down even worse on the new car from the instant you drive off the lot. Sell the current vehicle, find a way to pay the difference - one that doesn't involve financing. Cut your losses on the upside down vehicle. Then purchase a new vehicle. I'm in the \"\"Pay cash for gently used\"\" school, YMMV. Another option is to go to your bank. Refinance your car now to get a lower interest rate. Pay as much of the principal as you can. Keep that car until it is paid off. Then you will not be upside down. If you're asking how to use the estimator on the webpage. Put the payoff in the downpayment as a negative and the trade in value in the trade in spot. Expect the payment to go up significantly. Another opinion that might be practical advice. Nothing we say here will convince your financially responsible spouse that this is a good idea.\"",
"title": ""
},
{
"docid": "494616",
"text": "There are some who argue that you should lease an electric car. These factors are in addition to all the normal pros and cons of leasing vs. buying. The technology is still new and is advancing rapidly. In 2-3 years, the newer model may have significantly improved features, range, and efficiency, as well as lower prices. If you are the type of person to upgrade regularly to the latest and greatest, leasing can make it a smoother transition. It is hard to predict the depreciation of the vehicles. This is both because of the above factors, but also because these kinds of cars are newer and so the statistical models used to predict their future values are less refined. The models for predicting gas car prices have been honed for decades. EV Manufacturers have in the past made some mistakes in their residual value estimations. When you lease a car, you get essentially an option to buy the car at the future predicted residual value. If, at the end of the lease, the market value of the car is higher than the residual value, you can purchase the car at the predetermined price, making yourself some extra money. If the value is lower than the residual, you can return the car or renegotiate. I know a relatively large number of electric vehicle owners. Most or all of the ones who got the vehicle new leased it. The rest bought used vehicles coming off lease, which can also be a good deal.",
"title": ""
},
{
"docid": "545305",
"text": "Regarding auto insurance, you have to look at the different parts. In the United Sates most states do require a level of specific coverage for all drivers. That is to make sure that if you are at fault there is money available to pay the victims. That payment may be for damage to their car or other property, but it also covers medical costs. Many policies also cover you if the other driver doesn't have insurance. The policy that covers the loss of the vehicle is required if you have a loan or are leasing the car. Somebody else owns it while there is a loan, so they can and do require you to pay to protect the vehicle. If there i no loan you don't have to have that portion of a policy. Other parts such as towing, roadside assistance, and rental cars replacement may be required by the insurance standards for your state, or might be almost impossible to drop because all insurance companies include it to stay competitive with their competition. Dropping the non-required parts of the coverage is acceptable when you don't have a loan. Some people do drop it to save money. But that does mean you are self insuring. If you can afford to self insure a new car, great. The interesting thing is that some people have more than enough assets to self inure the non-required part of auto insurance. But then they realize that they do need to up their umbrella liability insurance. This is to protect them from somebody deciding that their resources make them a tempting target when they are involved in a collision.",
"title": ""
},
{
"docid": "346628",
"text": "\"I worked for a major car rental company (not Hertz, but comparable) for quite a while, taking reservations by phone. I completely agree that the reservation system is terrible, and is only vaguely based on the reality of their vehicles in stock at best. The problem is, from a strictly business perspective, taking more reservations than they have cars is currently considered the most profitable model for them. To play devil's advocate just a little, switching to a \"\"take only one reservation per vehicle, reserve it to 100% lock it in\"\" model is a bit more complicated than it sounds. In order to guarantee a specific car for a customer at a specific time, they either have to leave that car sitting on their lot until you rent it (not making money), or keep renting it out to other people in the interim. If they rent it out to someone else before your rental comes up, that removes the vehicle from their control. Bordering on constantly, renters don't return the vehicle within their promised schedule or return it in a damaged or otherwise unsuitable condition. To be clear I'm not trying to make excuses for the rental car company (there are many reasons I no longer work there), but it's objectively hard for them to get a specific vehicle if, say, all but one of them were in wrecks the previous night, and the person renting the last one drove it across the country without warning the rental office and refuses to come back. Those problems all get solved eventually, but that doesn't help you when you show up and can't get the car you reserved. So, they continue to take excessive reservations, and just give people whatever they happen to have when they show up, if they have any cars at all. There's definitely better ways to do it for the customer, but like many businesses, they'll continue to do it whatever way they determine is best for their profits. Edit: Words.\"",
"title": ""
},
{
"docid": "495710",
"text": "\"Hi there, I'm a Tesla owner. I think, for the Model S and X segment currently buying cars, you're right. Environmentalism isn't the first and foremost thing in their mind. However, that isn't to say being environmentally conscious isn't a credit they should receive for their purchase, because other informing factors, like charging at home instead of needing to refuel, is a perk AND it reduces oil/gas usage. I didn't buy my car to \"\"lower my carbon footprint\"\", as buying an EV doesn't necessarily do so in the big picture. I do, however, LOVE the fact I can charge my car at home and never visit a gas station. Every day, I get in my car with a \"\"full tank\"\", and I'm one less paying customer at the pump. As far as a status symbol, for me, it's the opposite. I don't want a showy, iconic vehicle that people will gawk at me over. I'm fairly low key, I'd rather not have the attention. I just needed/wanted a car with great interior cargo space, but was an electric vehicle I could charge at home. The Chevy Bolt, VW eGolf, Fiat 500e, and other EV options didn't fit the bill for me. Also, and most importantly, I wanted a vehicle that's future proofed (at least for a few years) to offer full self driving capability the moment it was allowed. Tesla became the icon for offering attractive electric vehicles at a time when most available options looked phoned in. Remember what you said in your first post: \"\"$500,000,000 loan for a car they've never seen and many won't receive for well over a year?\"\" A lot of people, myself included, never saw the \"\"official prototype\"\" until after we made our reservations on March 31, 2016. So the notion that it's purely an icon seems incomplete. I will say this, though: as soon as other auto makers take the EV market seriously, and design cars that actually look attractive, I think you'll see the Tesla demand drop for those who are looking for EV options pure and simple. I think, in the next few years, as more EV makers step up, what will differentiate the vehicles is the underlying tech in the car first and foremost, closely followed by design aesthetic. Tesla will retain buyers if they beat everyone to market with an available, fully self-driving capable vehicle, but they'll see some of that market shift away if other makers break in.\"",
"title": ""
},
{
"docid": "455851",
"text": "If you buy a new car, the odds that it will require repairs are fairly low, and if it does, they should be covered by the warranty. If you buy a used car, there is a fair chance that it will need some sort of repairs, and there probably is no warranty. But think about how much repairs are likely to cost. A new car these days costs like $25,000 or more. You can find reasonably decent used cars for a few thousand dollars. Say you bought a used car for $2,000. Is it likely that it will need $23,000 in repairs? No way. Even if you had to make thousands of dollars worth of repairs to the used car, it would almost certainly be cheaper than buying a new car. I've bought three used vehicles in the last few years, one for me, one for my son, and one for my daughter. I paid, let's see, I think between $4,000 and $6,000 each. We've had my son's car for about 9 months and to date had $40 in repairs. My daughter's car turned out to have a bunch of problems; I ended up putting maybe another $2,000 into it. But now she's got a car she's very happy with that cost me maybe $6,000 between purchase and repairs, still way less than a new car. My pickup had big time problems, including needing a new transmission and a new engine. I've put, hmm, maybe $7,000 into it. It's definitely debatable if it was worth replacing the engine. But even at all that, if I had bought that truck new it would have cost over $30,000. Presumably if I bought new I would have had a nicer vehicle and I could have gotten exactly the options I wanted, so I'm not entirely happy with how this one turned out, but I still saved money by buying used. Here's what I do when I buy a used car: I go into it expecting that there will be repairs. Depending on the age and condition of the car, I plan on about $1000 within the first few months, probably another $1000 stretched out over the next year or so. I plan for this both financially and emotionally. By financially I mean that I have money set aside for repairs or have available credit or one way or another have planned for it in my budget. By emotionally I mean, I have told myself that I expect there to be problems, so I don't get all upset when there are and start screaming and crying about how I was ripped off. When you buy a used car, take it for granted that there will be problems, but you're still saving money over buying new. Sure, it's painful when the repair bills hit. But if you buy a new car, you'll have a monthly loan payment EVERY MONTH. Oh, and if you have a little mechanical aptitude and can do at least some of the maintenance yourself, the savings are bigger. Bear in mind that while you are saving money, you are paying for it in uncertainty and aggravation. With a new car, you can be reasonably confidant that it will indeed start and get you to work each day. With a used car, there's a much bigger chance that it won't start or will leave you stranded. $2,000 is definitely the low end, and you say that that would leave you no reserve for repairs. I don't know where you live or what used cars prices are like in your area. Where I live, in Michigan, you can get a pretty decent used car for about $5,000. If I were you I'd at least look into whether I could get a loan for $4,000 or $5,000 to maybe get a better used car. Of course that all depends on how much money you will be making and what your other expenses are. When you're a little richer and better established, then if a shiny new car is important to you, you can do that. Me, I'm 56 years old, I've bought new cars and I've bought used cars and I've concluded that having a fancy new car just isn't something that I care about, so these days I buy used.",
"title": ""
}
] |
10337
|
Technical Analysis not working
|
[
{
"docid": "527105",
"text": "I would echo @Victor's comments. One book and 1000 web pages doesnt make you a good investor/trader. There are some basic things you should be aware of and read up on There are a few books that I would recommend I have been trading for over 10 years, my dad for over 30 years and we are both continually learning new things. Don't read one book and assume you know it all. Bear in mind that there are always new indicators being thought up and new ways of using and interpreting the same information, so keep reading and educating yourself.",
"title": ""
},
{
"docid": "432608",
"text": "\"You cannot just read one book and some articles on Technical Analysis and some indicators and expect to be an expert and everything to just start falling into place and give you signals that will tell you when to buy and sell with precision and massive profits all the time. It is like someone reading a book on how to drive a car and then expecting to drive flawlessly the first time they sit in the driver's seat, or someone reading a book on brain surgery and expecting to be able to operate on a live patient the next day. It looks like you are using 3 or 4 indicators to get daily buy and sell signals on a daily chart for an EFT you're looking to hold for decades. So firstly you are using short term indicators for a long term outlook. You need to decide what timeframe you plan to hold your investments for and use chart periods and indicators that suit that timeframe. Secondly, each indicator can be used in a number of ways and the settings you use for each indicator can determine whether you get earlier or later signals. Also, you need to work out which indicators work well together and are complementary, compared to those that don't work well together and give conflicting signals. All this information will come together for you the more you read about and practice the art of Technical Analysis. If your timeframe is very long-term (decades) I would be using mainly a weekly chart, with a longer period MA, the ROC indicator and possibly some trend lines. Keep it simple. The price itself is very important too. You can determine when a trend is starting or has ended purely using the price. The definition of an uptrend is higher highs and higher lows, so on the weekly chart if there is a lower high followed by a lower low - this could be the end of the uptrend. If we get a lower low followed by a lower high - this again could be the end of the uptrend. These could be a good time to start getting cautious and maybe looking to sell. If you are using stop losses (which I recommend) this may be a good time to tighten your stops. Similarly, a downtrend is defined as lower lows and lower highs. If we get a higher low followed by a higher high it could be the end of the downtrend and maybe the start of an uptrend. This could be a good time to start getting ready to buy. You need to learn about how and where to set your buy and sell orders (including stops) and whether you wait for confirmation when you get a signal. All this takes some time, but the more you read, the more you attend live events and the more you practice the more they will become second nature. In order to get the best out of Technical Analysis you will need to learn, plan, practice and execute. A good book to help you prepare your trading plan is \"\"Smart Trading Plans\"\" by Justine Pollard. One of my favourite books is \"\"The Complete Trading Course - Price Patterns, Strategies, Setups, and Execution Tactics\"\" by Corey Rosenbloom. And another good book is \"\"Trade your Way to Financial Freedom\"\" by Van Tharp.\"",
"title": ""
}
] |
[
{
"docid": "148019",
"text": "Technical Analysis in general is something to be cognizant of, I don't use a majority of studies and consider them a waste of time. I also use quantitative analysis more so than technical analysis, and prefer the insight it gives into the market. The markets are more about predicting other people's behavior, psychology. So if you are trading an equity that you know retail traders love, retail traders use technical analysis and you can use their fabled channel reversals and support levels against them, as examples. Technical analysis is an extremely broad subject. So I suggest getting familiar, but if your historical pricing charts are covered in various studies, I would say you are doing it wrong. A more objective criticism of technical analysis is that many of the studies were created in the 1980s or earlier. Edges in the market do not typically last more than a few weeks. On the other side of that realization, some technical analysis works if everyone also thinks it will work, if everyone's charts say buy when the stock reaches the $90 price level and everyone does, the then stock will go higher. But the market makers and the actions of the futures markets and the actions of options traders, can undermine the collective decisions of retail traders using technical analysis.",
"title": ""
},
{
"docid": "180644",
"text": "Your question is a bit odd in that you are mixing long-term fundamental analysis signals which are generally meant to work on longer time frames with medium term trading where these fundamental signals are mostly irrelevant. Generally you would buy-and-hold on a fundamental signal and ride the short-term fluctuations if you believe you have done good analysis. If you would like to trade on the 2-6 month time scale you would need a signal that works on that sort of time scale. Some people believe that technical analysis can give you those kind of signals, but there are many, many, many different technical signals and how you would trade using them is highly dependent on which one you believe works. Some people do mix fundamental and technical signals, but that can be very complicated. Learning a good amount about technical analysis could get you started. I will note, though, that studies of non-professionals continuously show that the more frequently people trade the more on they underperform on average in the long term when compared with people that buy-and-hold. An aside on technical analysis: michael's comment is generally correct though not well explained. Say Bob found a technical signal that works and he believes that a stock that costs $10 dollars should be $11. He buys it and makes money two months later when the rest of the market figures out the right price is $11 and he sells at that price. This works a bunch of times and he now publishes how the signal works on Stack Exchange to show everyone how awesome he is. Next time, Bob's signal finds a different stock at $10 that should be $11, but Anna just wrote a computer program that checks that signal Bob published faster than he ever could. The computer program buys as much as it can in milliseconds until the price is $11. Bob goes to buy, but now it is too late the price is already $11 and he can't make any money. Eventually, people learn to anticipate/adjust for this signal and even Anna's algorithms don't even work anymore and the hunt for new signals starts again.",
"title": ""
},
{
"docid": "508152",
"text": "\"Remember the 1st Law of Technical Analysis: \"\"For every analysis there exists an equal and opposite analysis.\"\" And the 2nd Law of Technical Analysis: \"\"They're both wrong.\"\" Technical analysis in the absence of hard data is just a lot of hand-waving meant to dazzle CNBC viewers and rope would-be day traders into paying for colored-plot-filled trading platforms. How, mathematically, do you define a bull trap? Does the lead in trendline have to have a certain minimum/maximum slope? Does the trough have to be below/above a certain percentage of the peaks? Does the entire period have to encompass less/more than a certain number of trading days? Etc. Before you attempt to use such an analysis to predict the future direction of a stock price you need to be able to answer the above questions (and more) rigorously. Only then can you test your definition against historical stock movements to see whether it has predictive power. If it doesn't have predictive power, then you start over or tweak your definition until it does. Notice that once you're done with all of the above work you are no longer doing technical analysis and are now doing statistics!\"",
"title": ""
},
{
"docid": "224695",
"text": "\"Below is just a little information on this topic from my small unique book \"\"The small stock trader\"\": The most significant non-company-specific factor affecting stock price is the market sentiment, while the most significant company-specific factor is the earning power of the company. Perhaps it would be safe to say that technical analysis is more related to psychology/emotions, while fundamental analysis is more related to reason – that is why it is said that fundamental analysis tells you what to trade and technical analysis tells you when to trade. Thus, many stock traders use technical analysis as a timing tool for their entry and exit points. Technical analysis is more suitable for short-term trading and works best with large caps, for stock prices of large caps are more correlated with the general market, while small caps are more affected by company-specific news and speculation…: Perhaps small stock traders should not waste a lot of time on fundamental analysis; avoid overanalyzing the financial position, market position, and management of the focus companies. It is difficult to make wise trading decisions based only on fundamental analysis (company-specific news accounts for only about 25 percent of stock price fluctuations). There are only a few important figures and ratios to look at, such as: perhaps also: Furthermore, single ratios and figures do not tell much, so it is wise to use a few ratios and figures in combination. You should look at their trends and also compare them with the company’s main competitors and the industry average. Preferably, you want to see trend improvements in these above-mentioned figures and ratios, or at least some stability when the times are tough. Despite all the exotic names found in technical analysis, simply put, it is the study of supply and demand for the stock, in order to predict and follow the trend. Many stock traders claim stock price just represents the current supply and demand for that stock and moves to the greater side of the forces of supply and demand. If you focus on a few simple small caps, perhaps you should just use the basic principles of technical analysis, such as: I have no doubt that there are different ways to make money in the stock market. Some may succeed purely on the basis of technical analysis, some purely due to fundamental analysis, and others from a combination of these two like most of the great stock traders have done (Jesse Livermore, Bernard Baruch, Gerald Loeb, Nicolas Darvas, William O’Neil, and Steven Cohen). It is just a matter of finding out what best fits your personality. I hope the above little information from my small unique book was a little helpful! Mika (author of \"\"The small stock trader\"\")\"",
"title": ""
},
{
"docid": "577498",
"text": "Technical analysis is based more on psychology than anything else. As an example, if an analyst estimates or believes that a stock is undervalued, or simply wants to re-balance their portfolio, then they will buy some amount, moving the price up. Others in the market see the upwards move as the start of an upwards trend, an indication that the stock is undervalued or perhaps even that an insider is trading ahead of better than expected data from the firm. They then buy the stock creating a self-fulfilling prophecy and pulling more traders in as they see an upward trend being confirmed. This is even more pronounced in a bear market as fear is an even stronger driver. When a trader sees a stock is falling they are more likely to jump to the conclusion that it is due to expected poor performance of the firm and that the firm and the economy are both in trouble and going down than to think that it is simply a retrenching or a large investor re-balancing etc. To quote Credit Suisse [1] A chart is a mirror of the mood of the crowd and not of the fundamental factors. Thus, technical analysis is the analysis of human mass psychology. Therefore, it is also called behavioral finance. The underlying truth that makes technical analysis work is that people are predictably irrational, at least in the short run and tend to follow the same patterns of thought. references: [1] https://www.credit-suisse.com/pwp/pb/pb_research/technical_tutorial_de.pdf [2] http://www.amazon.com/The-Psychology-Technical-Analysis-Profiting/dp/1557385432 [3] CFA level 1 syllabus",
"title": ""
},
{
"docid": "263464",
"text": "I'd recommend looking at fundamental analysis as well -- technical analysis seems to be good for buy and sell points, but not for picking what to buy. You can get better outperformance by buying the right stuff, and it can be surprisingly easy to create a formula that works. I'd check out Morningstar, AAII, or Equities Lab (fairly complicated but it lets you do technical and fundamental analysis together). Also read Benjamin Graham, and/or Ken Fisher (they are wildly different, which is why I recommend them both).",
"title": ""
},
{
"docid": "55002",
"text": "\"Your questions In the world of technical analysis, is candlestick charting an effective trading tool in timing the markets? It depends on how you define effective. But as a standalone and systematic strategy, it tends not to be profitable. See for example Market Timing with Candlestick Technical Analysis: Using robust statistical techniques, we find that candlestick trading rules are not profitable when applied to DJIA component stocks over 1/1/1992 – 31/12/2002 period. Neither bullish or bearish candlestick single lines or patterns provide market timing signals that are any better than what would be expected by chance. Basing ones trading decisions solely on these techniques does not seem sensible but we cannot rule out the possibility that they compliment some other market timing techniques. There are many other papers that come to the same conclusion. If used correctly, how accurate can they be in picking turning points in the market? Technical analysts generally fall into two camps: (i) those that argue that TA can't be fully automated and that interpretation is part of the game; (ii) those that use TA as part of a systematic investment model (automatically executed by a machine) but generally use a combination of indicators to build a working model. Both groups would argue (for different reasons) that the conclusions of the paper I quoted above should be disregarded and that TA can be applied profitably with the proper framework. Psychological biases It is very easy to get impressed by technical analysis because we all suffer from \"\"confirmation bias\"\" whereby we tend to acknowledge things that confirm our beliefs more than those that contradict them. When looking at a chart, it is very easy to see all the occurences when a certain pattern worked and \"\"miss\"\" the occurences when it did not work (and not missing those is much harder than it sounds). Conclusions\"",
"title": ""
},
{
"docid": "442897",
"text": "I recall the name Martin Pring. As my fundamental analysis book from grad school was the work of Graham and Dodd titled Security Analysis, Pring was the author of the books I read on technical analysis. If you've not read his work, your education has a ways to go before you hit the tools.",
"title": ""
},
{
"docid": "367391",
"text": "\"Strategy would be my top factor. While this may be implied, I do think it helps to have an idea of what is causing the buy and sell signals in speculating as I'd rather follow a strategy than try to figure things out completely from scratch that doesn't quite make sense to me. There are generally a couple of different schools of analysis that may be worth passing along: Fundamental Analysis:Fundamental analysis of a business involves analyzing its financial statements and health, its management and competitive advantages, and its competitors and markets. When applied to futures and forex, it focuses on the overall state of the economy, interest rates, production, earnings, and management. When analyzing a stock, futures contract, or currency using fundamental analysis there are two basic approaches one can use; bottom up analysis and top down analysis. The term is used to distinguish such analysis from other types of investment analysis, such as quantitative analysis and technical analysis. Technical Analysis:In finance, technical analysis is a security analysis methodology for forecasting the direction of prices through the study of past market data, primarily price and volume. Behavioral economics and quantitative analysis use many of the same tools of technical analysis, which, being an aspect of active management, stands in contradiction to much of modern portfolio theory. The efficacy of both technical and fundamental analysis is disputed by the efficient-market hypothesis which states that stock market prices are essentially unpredictable. There are tools like \"\"Stock Screeners\"\" that will let you filter based on various criteria to use each analysis in a mix. There are various strategies one could use. Wikipedia under Stock Speculator lists: \"\"Several different types of stock trading strategies or approaches exist including day trading, trend following, market making, scalping (trading), momentum trading, trading the news, and arbitrage.\"\" Thus, I'd advise research what approach are you wanting to use as the \"\"Make it up as we go along losing real money all the way\"\" wouldn't be my suggested approach. There is something to be said for there being numerous columnists and newsletter peddlers if you want other ideas but I would suggest having a strategy before putting one's toe in the water.\"",
"title": ""
},
{
"docid": "396657",
"text": "The study of technical analysis is generally used (sometimes successfully) to time the markets. There are many aspects to technical analysis, but the simplest form is to look for uptrends and downtrends in the charts. Generally higher highs and higher lows is considered an uptrend. And lower lows and lower highs is considered a downtrend. A trend follower would go with the trend, for example see a dip to the trend-line and buy on the rebound. A simple strategy for this is shown in the chart below: I would be buying this stock when the price hits or gets very close to the trendline and then it bounces back above it. I would then have sold this stock once it has broken through below the trendline. This may also be an appropriate time if you were looking to short this stock. Other indicators could also be used in combination for additional confirmation of what is happening to the price. Another type of trader is called a bottom fisher. A bottom fisher would wait until a break above the downtrend line (second chart) and buy after confirmation of a higher high and possibly a higher low (as this could be the start of a new uptrend). There are many more strategies dealing with the study of technical analysis, and if you are interested you would need to find and learn about ones that suit your investment styles, whether you prefer short term trading or longer term investing, and your appetite for risk. You can develop strategies using various indicators and then paper trade or backtest these strategies. You can also manually backtest a strategy in most charting packages. You can go back in time on the chart so that the right side of the chart shows a date in the past (say one year ago or 10 years ago), then you can click forward one day at a time (or one week at a time if using weekly charts). With your indicators on the chart you can do virtual trades to buy or sell whenever a signal is given as you move forward in time. This way you may be able to check years of data in a day to see if your strategy works. Whatever you do, you need to document your strategies in writing in a written trading or investment plan together with a risk management strategy. You should always follow the rules in your written plan to avoid you making decisions based on emotions. By backtesting or paper trading your strategies it will give you confidence that they will work over the long term. There is a lot of work involved at the start, but once you have developed a documented strategy that has been thoroughly backtested, it will take you minimal time to successfully manage your investments. In my shorter term trading (positions held from a couple of days to a few weeks) I spend about half an hour per night to manage my trades and am up about 50% over the last 7 months. For my longer term investing (positions held from months to years) I spend about an hour per week and have been averaging over 25% over the last 4 years. Technical Analysis does work for those who have a documented plan, have approached it in a systematic way and use risk management to protect their existing and future capital. Most people who say that is doesn't work either have not used it themselves or have used it ad-hock without putting in the initial time and work to develop a documented and systematic approach to their trading or investing.",
"title": ""
},
{
"docid": "377466",
"text": "\"A lot of investors prefer to start jumping into tools and figuring out from there, but I've always said that you should learn the theory before you go around applying it, so you can understand its shortcomings. A great starting point is Investopedia's Introduction to Technical Analysis. There you can read about the \"\"idea\"\" of technical analysis, how it compares to other strategies, what some of the big ideas are, and quite a bit about various chart patterns (cup and handle, flags, pennants, triangles, head & shoulders, etc). You'll also cover ideas like moving averages and trendlines. After that, Charting and Technical Analysis by Fred McAllen should be your next stop. The material in the book overlaps with what you've read on Investopedia, but McAllen's book is great for learning from examples and seeing the concepts applied in action. The book is for new comers and does a good job explaining how to utilize all these charts and patterns, and after finishing it, you should be ready to invest on your own. If you make it this far, feel free to jump into Fidelity's tools now and start applying what you've learned. You always want to make the connection between theory and practice, so start figuring out how you can use your new knowledge to generate good returns. Eventually, you should read the excellent reference text Technical Analysis of the Financial Markets by John Murphy. This book is like a toolbox - Murphy covers almost all the major techniques of technical analysts and helps you intuitively understand the reasoning behind them. I'd like to quote a part of a review here to show my point: What I like about Mr. Murphy is his way of showing and proving a point. Let me digress here to show you what I mean: Say you had a daughter and wanted to show her how to figure out the area of an Isosceles triangle. Well, you could tell her to memorize that it is base*height/2. Or if you really wanted her to learn it thoroughly you can show her how to draw a parallel line to the height, then join the ends to make a nice rectangle. Then to compute the area of a rectangle just multiply the two sides, one being the height, the other being half the base. She will then \"\"derive\"\" this and \"\"understand\"\" how they got the formula. You see, then she can compute the area under a hexagon or a tetrahedron or any complex object. Well, Mr. Murphy will show us the same way and \"\"derive\"\" for us concepts such as how a resistance line later becomes a support line! The reson for this is so amusing that after one reads about it we just go \"\"wow...\"\"\"\" Now I understand why this occurs\"\". Murphy's book is not about strategy or which tools to use. He takes an objective approach to describing the basics about various tools and techniques, and leaves it up to the reader to decide which tools to apply and when. That's why it's 576 pages and a great reference whenever you're working. If you make it through and understand Murphy, then you'll be golden. Again, understand the theory first, but make sure to see how it's applied as well - otherwise you're just reading without any practical knowledge. To quote Richard Feynman: It doesn't matter how beautiful your theory is, it doesn't matter how smart you are. If it doesn't agree with experiment, it's wrong. Personally, I think technical analysis is all BS and a waste of time, and most of the top investors would agree, but at the end of the day, ignore everyone and stick to what works for you. Best of luck!\"",
"title": ""
},
{
"docid": "305117",
"text": "From my experience you don't need knowledge of accounting to pick good stocks. The type of investing you are referring to is fundamental. This is finding out about the company, this websites should help you start off: http://en.tradehero.mobi/how-to-choose-a-stock-fundamental-analysis/ Investopedia will also be a useful website in techniques. A bit of knowledge in economics will be helpful in understanding how current affairs will affect a market, which will affect stock prices. However you need neither economics or accounting knowledge if you were to learn technical analysis, many doubt the workings of this technique, but in my experience it is easier to learn and practise. For example looking at charts from previous years it shows the last time there was a huge recession the dollar did well and commodities didn't. In this recession we are entering you can see the same thing happening. Read about the different techniques before limiting yourself to just looking at financial statements you may find a better technique suited to you, like these technical analysts: http://etfhq.com/blog/2013/03/02/top-technical-analysts/ Hope this helps.",
"title": ""
},
{
"docid": "204297",
"text": "\"I interned for about six months at a firm that employed a few technical analysts, so I'll try to provide what little information I can. Since the bulk of the intra-day trading was decided algorithmically, technical analysts had two main functions: This basically boils down to my answer to your question. There are still enough people, trading firms, etc. who believe in candlestick charting and other visually subjective patterns that if you notice a trend, pattern, etc. before the majority of traders observing, you may be able to time the market successfully and profit. This is becoming increasingly dangerous, however, because of the steps I outlined above. Over time, the charting patterns that have been proven effective (often in many firms individually since the algorithms are all proprietary) are incorporated into computer algorithms, so the \"\"traders\"\" you're competing with to see the pattern are increasingly low-latency computer clusters less than a few blocks from the exchange. Summary: Candlestick charting, along with other forms of subjective technical analysis, has its believers, and assuming enough of these believers trade the standard strategies based on the standard patterns, one could conceivably time the market with enough skill to anticipate these traders acting on the pattern and therefore profit. However, the marginal benefits of doing so are decreasing rapidly as computers take over more trading responsibility. Caveats: I know you're in Australia, where the market penetration of HF/algo traders isn't as high as in the US, so it might be a few more years before the marginal benefits cease to be profitable; that being said, if various forms of technical analysis proved wildly profitable in Australia, above and beyond profits available in other markets, rest assured that large American or British trading firms would already have moved in. My experience is limited to one trading firm, so I certainly can't speak for the industry as a whole. I know I didn't address candlestick charts specifically, but since they're only one piece of visual technical analysis, I tried to address the issue as a whole. This somewhat ties into the debate between fundamental or technical analysis, which I won't get into. Investopedia has a short article on the subject. As I said, I won't get into this because while it's a nice debate for small traders, at large trading firms, they don't care; they want to make profit, and any strategy that can be vetted, whether it's fundamental, technical, or astrological, will be vetted. I want to add more information to my answer to clear up some of the misconceptions in the comments, including those talking about biased studies and a lack of evidence for or against technical analysis (and candlestick charts; I'll explore this relationship further down). It's important to keep in mind that charting methods, including candlestick charts, are visually subjective ways of representing data, and that any interpretations drawn from such charts should, ideally, represent objective technical indicators. A charting method is only as good as the indicators it's used to represent. Therefore, an analysis of the underlying indicators provides a suitable analysis for the visual medium in which they're presented. One important study that evaluates several of these indicators is Foundations of Technical Analysis: Computational Algorithms, Statistical Inference, and Empirical Implementation by Lo, Mamaysky, and Wang. Lest anyone accuse its authors of bias, I should point out that not only is it published by the National Bureau of Economic Research (a highly reputable organization within economics and finance), but also that the majority of its authors come from MIT's Sloan school, which holds a reputation second to none. This study finds that several technical indicators, e.g. head-and-shoulder, double-bottom, and various rectangle techniques, do provide marginal value. They also find that although human judgment is still superior to most computational algorithms in the area of visual pattern recognition, ... technical analysis can be improved by using automated algorithms Since this paper was published in 2000, computing power and statistical analysis have gained significant ground against human ability to identify and exploit for visual pattern detection like candlestick charts. Second, I suggest you look into David Aaronson's book, Evidence-Based Technical Analysis: Applying the Scientific Method and Statistical Inference to Trading Signals. He finds similar results to the Lo, et. al. paper, in that some technical indicators do add value to the investment process, but those that do are those that can be represented mathematically and thus programmed directly into trading algorithms (thus bypassing visual tools like candlestick charts). He describes how studies, including Lo, et al., have found that head and shoulders patterns are worse than random, i.e. you would earn higher returns if you simply traded at random. That point is worth than repeating. If a day-trader is using a candlestick chart and using head-and-shoulders patterns as part of their toolkit, he's rolling the dice when he uses that pattern and returns that come from its application come from chance. This reminds me of that old story about a company that sends out pamphlets predicting the results of sports games, complete with \"\"strategies\"\" and \"\"data\"\" to back up the predictions. The company sends out several versions of the pamphlet every game, each predicting a different winner. Given a large enough sample size, by the end of the season, there are a few people who have received a pamphlet that accurately predicted the winner for every game and they're convinced the system is perfect. The others weren't so lucky, however. Relying on candlestick charts and TA patterns that are relics from the pre-computerized era is reassuring to some traders and gives them a sense of control and \"\"beating the market,\"\" but how long will chance remain on your side? This is why I maintain that visual tools like candlestick charts are a slowly dying medium. They certainly still add value to some trading firms, which is why Bloomberg terminals still ship with this functionality built in, but as more and more research shows, automated algorithms and statistical indicators can provide more value. It's also important to think about whether the majority of the value added by visual tools like candlestick charts comes in the form of profit or a sense of security to traders who learned the field using them over the past few decades. Finally, it's extremely important to realize that the actions of retail investors in the equities market cannot begin to represent the behaviors of the market as a whole. In the equities markets alone, trading firms and institutional investors dwarf retail investors, and the difference in scale is even more vastly pronounced in derivatives and currency markets. The fact that some retail investors use candlestick charts and the technical indicators they (hope) underlie them provides nothing but minor anecdotal evidence as to their effectiveness.\"",
"title": ""
},
{
"docid": "129309",
"text": "\"I was wondering how \"\"future cash flows of the asset\"\" are predicted? Are they also predicted using fundamental and/or technical analysis? There are a many ways to forecast the future cash flows of assets. For example, for companies: It seems like calculating expected/required rate using CAPM does not belong to either fundamental or technical analysis, does it? I would qualify the CAPM as quantitative analysis because it's mathematics and statistics. It's not really fundamental since its does not relies on economical data (except the prices). And as for technical analysis, the term is often used as a synonym for graphical analysis or chartism, but quantitative analysis can also be referred as technical analysis. the present value of future cash flows [...] (called intrinsic price/value, if I am correct?) Yes you are correct. I wonder when deciding whether an asset is over/fair/under-valued, ususally what kind of price is compared to what other kind of price? If it's only to compare with the price, usually, the Net asset value (which is the book value), the Discount Cash flows (the intrinsic value) and the price of comparable companies and the CAPM are used in comparison to current market price of the asset that you are studying. Why is it in the quote to compare the first two kinds of prices, instead of comparing the current real price on the markets to any of the other three kinds? Actually the last line of the quote says that the comparison is done on the observed price which is the market price (the other prices can't really be observed). But, think that the part: an asset is correctly priced when its estimated price is the same as the present value of future cash flows of the asset means that, since the CAPM gives you an expected rate of return, by using this rate to compute the present value of future cash flows of the asset, you should have the same predicted price. I wrote this post explaining some valuation strategies. Maybe you can find some more information by reading it.\"",
"title": ""
},
{
"docid": "185809",
"text": "The study of technical analysis is generally used (sometimes successfully) to time the markets. There are many aspects to technical analysis, but the simplest form is to look for uptrends and downtrends in the charts. Generally higher highs and higher lows is considered an uptrend. And lower lows and lower highs is considered a downtrend. A trend follower would go with the trend, for example see a dip to the trend-line and buy on the rebound. Whilst a bottom fisher would wait until a break in the downtrend line and buy after confirmation of a higher high (as this could be the start of a new uptrend). There are many more strategies dealing with the study of technical analysis, and if you are interested you would need to find and learn about ones that suit your investment styles and your appetite for risk.",
"title": ""
},
{
"docid": "120288",
"text": "Technical Analysis assumes that the only relevant number(s) regarding a security is (are) price (and price momentum, price patterns, price harmonics, price trends, price aberrations, etc.). Technical is all based on price. Technical is not based on any of the fundamentals. Technical Analysis is for traders (speculators) not for long term investors. A long term investor is more concerned with the dividend payment history and such similar data as he makes his money from the dividend payments not from the changes in price (because he buys and holds, not buy low sell high).",
"title": ""
},
{
"docid": "324779",
"text": "In fact markets are not efficient and participants are not rational. That is why we have booms and busts in markets. Emotions and psychology play a role when investors and/or traders make decisions, sometimes causing them to behave in unpredictable or irrational ways. That is why stocks can be undervalued or overvalued compared to their true value. Also, different market participants may put a different true value on a stock (depending on their methods of analysis and the information they use to base their analysis on). This is why there are always many opportunities to profit (or lose your money) in liquid markets. Doing your research, homework, or analysis can be related to fundamental analysis, technical analysis, or a combination of the two. For example, you could use fundamental analysis to determine what to buy and then use technical analysis to determine when to buy. To me, doing your homework means to get yourself educated, to have a plan, to do your analysis (both FA and TA), to invest or trade according to your plan and to have a risk management strategy in place. Most people are too lazy to do their homework so will pay someone else to do it for them or they will just speculate (on the latest hot tip) and lose most of their money.",
"title": ""
},
{
"docid": "425020",
"text": "I think by definition there aren't, generally speaking, any indicators (as in chart indicators, I assume you mean) for fundamental analysis. Off the top of my head I can't think of one chart indicator that I wouldn't call 'technical', even though a couple could possibly go either way and I'm sure someone will help prove me wrong. But the point I want to make is that to do fundamental analysis, it is most certainly more time consuming. Depending on what instrument you're investing in, you need to have a micro perspective (company specific details) and a macro perspective (about the industry it's in). If you're investing in sector ETFs or the like, you'd be more reliant on the macro analysis. If you're investing in commodities, you'll need to consider macro analysis in multiple countries who are big producers/consumers of the item. There's no cut and dried way to do it, however I personally opt for a macro analysis of sector ETFs and then use technical analysis to determine my entry and/or exit.",
"title": ""
},
{
"docid": "81655",
"text": "Fundamental Analysis can be used to help you determine what to buy, but they won't give you an entry signal for when to buy. Technical Analysis can be used to help you determine when to buy, and can give you entry signals for when to buy. There are many Technical Indicator which can be used as an entry signal, from as simple as the price crossing above a moving average line and then selling when the price crosses back below the moving average line, to as complicated as using a combination of indicators to all line up for an entry signal to be valid. You need to find the entry signals that would suit your investing or trading and incorporate them as part of your trading plan. If you want to learn more about entry signals you are better off learning more about Technical Analysis.",
"title": ""
},
{
"docid": "484897",
"text": "To answer your original question: There is proof out there. Here is a paper from the Federal Reserve Bank of St. Louis that might be worth a read. It has a lot of references to other publications that might help answer your question(s) about TA. You can probably read the whole article then research some of the other ones listed there to come up with a conclusion. Below are some excerpts: Abstract: This article introduces the subject of technical analysis in the foreign exchange market, with emphasis on its importance for questions of market efficiency. “Technicians” view their craft, the study of price patterns, as exploiting traders’ psychological regularities. The literature on technical analysis has established that simple technical trading rules on dollar exchange rates provided 15 years of positive, risk-adjusted returns during the 1970s and 80s before those returns were extinguished. More recently, more complex and less studied rules have produced more modest returns for a similar length of time. Conventional explanations that rely on risk adjustment and/or central bank intervention do not plausibly justify the observed excess returns from following simple technical trading rules. Psychological biases, however, could contribute to the profitability of these rules. We view the observed pattern of excess returns to technical trading rules as being consistent with an adaptive markets view of the world. and The widespread use of technical analysis in foreign exchange (and other) markets is puzzling because it implies that either traders are irrationally making decisions on useless information or that past prices contain useful information for trading. The latter possibility would contradict the “efficient markets hypothesis,” which holds that no trading strategy should be able to generate unusual profits on publicly available information—such as past prices—except by bearing unusual risk. And the observed level of risk-adjusted profitability measures market (in)efficiency. Therefore much research effort has been directed toward determining whether technical analysis is indeed profitable or not. One of the earliest studies, by Fama and Blume (1966), found no evidence that a particular class of TTRs could earn abnormal profits in the stock market. However, more recent research by Brock, Lakonishok and LeBaron (1992) and Sullivan, Timmermann an d White (1999) has provided contrary evidence. And many studies of the foreign exchange market have found evidence that TTRs can generate persistent profits (Poole 6 (1967), Dooley and Shafer (1984), Sweeney (1986), Levich and Thomas (1993), Neely, Weller and Dittmar (1997), Gençay (1999), Lee, Gleason and Mathur (2001) and Martin (2001)).",
"title": ""
},
{
"docid": "361976",
"text": "I love technical analysis, and use candlesticks as part of my technical analysis system for trading mutual funds in my 401K. However, I would never use a candlestick chart on its own. I use combination of candlesticks, 2 different EMAs, MACD, bollinger bands, RSI and hand drawn trend lines that I constantly tweak. That's about as much data input as I can handle, but it is possible to graph it all at once and see it at a glance if you have the right trading platform. My approach is very personal, not very aggressive, and took me years to develop. But it's fairly effective - 90% + of my trades are winners. The big advantage of technical analysis is that it forces you to create repeatable rules around which you base your trading. A lot of the time I have little attention at all on what fund I am trading or why it is doing well in that particular market condition. It's basically irrelevant as the technical system tells when to buy and sell, and stops you trying to second guess whether housing, chemicals, gold or asian tigers are is doing well right now. If you don't keep to your own rules, you have only yourself to blame. This keeps you from blaming the market, which is completely out of your control. I explain many of my trades with anotated graphs at http://neurotrade.blogspot.com/",
"title": ""
},
{
"docid": "221277",
"text": "There are Patterns inside of Patterns. You will see short term patterns (flags / pennants) inside of long term patterns (trend lines, channels) and typically you want to trade those short term patterns in line with the direction of the long term pattern. Take a look at the attached chart of GPN. I would like to recommend two excellent books on Chart Patterns. Richard W. Schabacker book he wrote in the 1930's. It is the basis for modern technical pattern analysis. Technical Analysis and Stock Market Profits Peter Brandt Diary of a Professional Commodity Trader. He takes you through analysis and trades.",
"title": ""
},
{
"docid": "169076",
"text": "It is called the Monday Effect or the Weekend Effect. There are a number of similar theories including the October Effect and January Effect. It's all pretty much bunk. If there were any truth to traders would be all over it and the resulting market forces would wipe it out. Personally, I think all technical analysis has very little value other than to fuel conversations at dinner parties about investments. You might also consider reading about Market efficiency to see further discussion about why technical approaches like this might, but probably don't work.",
"title": ""
},
{
"docid": "275171",
"text": "\"I (and probably most considering trading) had a similar thought as you. I thought if I just skimmed the peaks and sold before the troughs, perhaps aided by computer, I'd be able to make a 2% here, 2% there, and that would add up quickly to a nice amount of money. It almost did seem \"\"foolproof\"\". Then I realized that sometimes a stock just slides...down...and there is no peak higher than what I bought it for. \"\"That's OK,\"\" I'd think, \"\"I'm sure it will recover and surpass the price I bought it for...so now I play the waiting game.\"\" But then it continues sliding, and my $10k is now worth $7k. Do I sell? Did I build a stop loss point into my computer program? If so, what is the right place to put that stop? What if there is a freak dip down and it triggers the stop loss but THEN my stock recovers? I just lost $14,000 like this last week--luckily, only virtually! The point is, your idea only has half a chance to work when there is a mildly volatile stock that stays around some stable baseline, and even then it is not easy. And then you factor in fees as others mentioned... People do make money doing this (day traders), and some claim you can use technical analysis to time orders well, so if you want to try that, read about technical analysis on this site or elsewhere.\"",
"title": ""
},
{
"docid": "504992",
"text": "They do pitchdecks every week with the industry coverage groups presenting biweekly. Fundamental analysis included industry overview/company overview/investment rationale/valuation (usually DCF or public comps)/risk. PM then uses pitchdeck and technical analysis to set orders but buys the stock for the long run and makes and monitors it daily. 21% in a year and high growth picks by the OC for industries in tech usually are high growth so cap gains there are evn higher U probably went to some retard school. I said back office bc I highly doubt your dumb ass works in IB based on how socially incompetent and arrogant u sound.",
"title": ""
},
{
"docid": "111091",
"text": "\"Unfortunately, there is very little data supporting fundamental analysis or technical analysis as appropriate tools to \"\"time\"\" the market. I will be so bold to say that technical analysis is meaningless. On the other hand, fundamental analysis has some merits. For example, the realization that CDOs were filled with toxic mortgages can be considered a product of fundamental analysis and hence provided traders with a directional assumption to buy CDSs. However, there is no way to tell when there is a good or bad time to buy or sell. The market behaves like a random 50/50 motion. There are many reasons for this and interestingly, there are many fundamentally sound companies that take large dips for no reason at all. Depending on your goal, you can either believe that this volatility will smooth over long periods and that the market has generally positive drift. On the other hand, I feel that the appropriate approach is to remain active. You will be able to mitigate the large downswings by simply staying small and diversifying - not in the sense of traditional finance but rather looking for uncorrelated products. Remember, volatility brings higher levels of correlation. My second suggestion is to look towards products like options to provide a method of shaping your P/L - giving up upside by selling calls against a long equity position is a great example. Ground your trades with fundamental beliefs if need be, but use your tools and knowledge to combat risks that may create long periods of drawdown.\"",
"title": ""
},
{
"docid": "590879",
"text": "I would go even farther than Victor's answer. There is little evidence that candlestick patterns and technical analysis in general have any predictive power. Even if they did in the past, of which there is some evidence, in modern times they are so easy to do on computers that if they worked algorithmic traders would have scanned almost all traded stocks and bought/sold the stock before you even had a chance to look at the graph. While the best technical traders who are very good at quickly using pattern recognition across many indicators as Victor mentioned might be able to add some advantage. The odds that a pattern so simple to code such as Bullish Engulfing would have predictive power is tiny.",
"title": ""
},
{
"docid": "142320",
"text": "\"Most articles on investing recommend that investors that are just starting out to invest in index stock or bonds funds. This is the easiest way to get rolling and limit risk by investing in bonds and stocks, and not either one of the asset classes alone. When you start to look deeper into investing there are so many options: Small Cap, Large Cap, technical analysis, fundamental analysis, option strategies, and on and on. This can end up being a full time job or chewing into a lot of personal time. It is a great challenge to learn various investment strategies frankly for the average person that works full time it is a huge effort. I would recommend also reading \"\"The Intelligent Asset Allocator\"\" to get a wider perspective on how asset allocation can help grow a portfolio and reduce risk. This book covers a simple process.\"",
"title": ""
},
{
"docid": "194240",
"text": "\"One idea: If you came up with a model to calculate a \"\"fair price range\"\" for a stock, then any time the market price were to go below the range it could be a buy signal, and above the range it could be a sell signal. There are many ways to do stock valuation using fundamental analysis tools and ratios: dividend discount model, PEG, etc. See Wikipedia - Stock valuation. And while many of the inputs to such a \"\"fair price range\"\" calculation might only change once per quarter, market prices and peer/sector statistics move more frequently or at different times and could generate signals to buy/sell the stock even if its own inputs to the calculation remain static over the period. For multinationals that have a lot of assets and income denominated in other currencies, foreign exchange rates provide another set of interesting inputs. I also think it's important to recognize that with fundamental analysis, there will be extended periods when there are no buy signals for a stock, because the stocks of many popular, profitable companies never go \"\"on sale\"\", except perhaps during a panic. Moreover, during a bull market and especially during a bubble, there may be very few stocks worth buying. Fundamental analysis is designed to prevent one from overpaying for a stock, so even if there is interesting volume and price movement for the stock, there should still be no signal if that action happens well beyond the stock's fair price. (Otherwise, it isn't fundamental analysis — it's technical analysis.) Whereas technical analysis can, by definition, generate far more signals because it largely ignores the fundamentals, which can make even an overvalued stock's movement interesting enough to generate signals.\"",
"title": ""
},
{
"docid": "56065",
"text": "Cool! Financial IT is fun. Banks wouldn't run without us :). I'm doing a Master's while working part time in IT in an investment bank. I'm kind of on the fence of if I should go for a more technical profile (software development) or business profile (IT business analysis). It's quite the different career tracks...",
"title": ""
}
] |
PLAIN-2431
|
Flame Retardant Pollutants and Child Development
|
[
{
"docid": "MED-2656",
"text": "The aim of previous research into the causes of allergic diseases, including asthma was mostly to identify potential risk factors in the environment. No major risk factors have been identified, however. Over the past 10 years, focus has, therefore, more been directed towards protective factors that could enhance the development of tolerance to allergens which were previously encountered early in life, but are now lost in modern affluent societies. In particular, the role of childhood infections has been discussed, but so far these studies have not been conclusive. Recent epidemiological studies and experimental research suggest that the microbial environment and exposure to microbial products in infancy modifies immune responses and enhances the development of tolerance to ubiquitous allergens. The intestinal microflora may play a particular role in this respect, as it is the major external driving force in the maturation of the immune system after birth, and animal experiments have shown it to be a prerequisite for normal development of oral tolerance. Recent studies have shown differences in the composition of the microflora between healthy and allergic infants in countries with a high and low prevalence of allergies and between healthy and allergic infants within such countries. These differences are apparent within the first week of life and thus precede clinical symptoms. The use of live microorganisms that might be beneficial to health has a long tradition and the safety is well documented. Very recently, several prospective intervention studies, modifying the gut flora from birth have yielded encouraging results and may suggest a new mode of primary prevention of allergy in the future.",
"title": "Effects of intestinal microflora and the environment on the development of asthma and allergy."
},
{
"docid": "MED-2644",
"text": "Alkylphenols are widely used as plastic additives and surfactants. We report the identification of an alkylphenol, nonylphenol, as an estrogenic substance released from plastic centrifuge tubes. This compound was extracted with methanol, purified by flash chromatography and reverse-phase high performance liquid chromatography, and identified by gas chromatography-mass spectrometry. Nonylphenol induced both cell proliferation and progesterone receptor in human estrogen-sensitive MCF7 breast tumor cells. Nonylphenol also triggered mitotic activity in rat endometrium; this result confirms the reliability of the MCF7 cell proliferation bioassay. The estrogenic properties of alkylphenols, specifically nonylphenols, indicate that the use of plasticware containing these chemicals in experimental and diagnostic tests may lead to spurious results, and these compounds as well as alkylphenol polyethoxylates may also be potentially harmful to exposed humans and the environment at large.",
"title": "p-Nonyl-phenol: an estrogenic xenobiotic released from \"modified\" polystyrene."
},
{
"docid": "MED-4727",
"text": "The objective of this study was to estimate the intake of organic tin compounds from foodstuffs in a Finnish market basket. The study was conducted by collecting 13 market baskets from supermarkets and market places in the city of Kuopio, eastern Finland. Altogether 115 different food items were bought. In each basket, foodstuffs were mixed in proportion to their consumption and analysed by GC/MS for seven organic tin compounds (mono-, di-, and tributyltin, mono-, di-, and triphenyltin, and dioctyltin). Organotin compounds were detected in only four baskets, with the fish basket containing the largest number of different organotins. The European Food Safety Authority has established a tolerable daily intake of 250 ng kg(-1) body weight for the sum of dibutyltin, tributyltin, triphenyltin and dioctyltin. According to this study, the daily intake of these compounds was 2.47 ng kg(-1) body weight, of which 81% originated from the fish basket. This exposure is only 1% of the tolerable daily intake and poses negligible risk to the average consumer. However, for consumers eating large quantities of fish from contaminated areas, the intake may be much higher.",
"title": "Dietary intake of organotin compounds in Finland: a market-basket study."
},
{
"docid": "MED-2652",
"text": "The exposure to some chemicals can lead to hormone disrupting effects. Presently, much attention is focused on so-called xeno-estrogens, synthetic compounds that interact with hormone receptors causing a number of reactions that eventually lead to effects related to reproduction and development. The current study was initiated to investigate the presence of a number of such compounds in precipitation as a follow-up on a previous study in which pesticide concentrations in air and precipitation were determined. Rainwater samples were collected at about 50 locations in The Netherlands in a four week period. The samples were analysed for bisphenol-A, alkylphenols and alkylphenol ethoxylates, phthalates, flame retardants and synthetic musk compounds. The results clearly indicated the presence of these compounds in precipitation. The concentrations ranged from the low ng l(-1) range for flame retardants to several thousands of ng l(-1) for the phthalates. Bisphenol-A was found in 30% of the samples in concentrations up to 130 ng l(-1), while alkylphenols and alkylphenol ethoxylates were found in virtually all locations in concentrations up to 920 ng l(-1) for the individual compounds. Phthalates were by far the most abundant xeno-estrogens in the precipitation samples and were found in every sample. Di-isodecyl phthalate was found in a surprisingly high concentration of almost 100 000 ng l(-1). Polybrominated flame retardants were found in the low ng l(-1) range and generally in less than 20% of the samples. Noticeable was the finding of hexabromocyclododecane, a replacement for the polybrominted diphenyl ethers at one location in a concentration of almost 2000 ng l(-1). Finally, as expected, synthetic musk compounds were detected in almost all samples. This is especially true for the polycyclic musks HHCB and AHTN. Nitro musks were found, but only on a few locations. Kriging techniques were used to calculate precipitation concentrations in between actual sampling locations to produce contour plots for a number of compounds. These plots clearly show located emission sources for a number of compounds such as bisphenol-A, nonylphenol ethoxylate, phthalates and AHTN. On the contrary, the results for HHCB and some phthalates indicated diffuse emission patterns, probably as the result of the use of consumer products containing these compounds.",
"title": "Xeno-estrogenic compounds in precipitation."
},
{
"docid": "MED-2650",
"text": "Over the last 40 years there have been constant reports concerning environmental chemicals with hormone-like effects in wildlife. An endocrine disruptor is an exogenous substance that causes adverse health effects in an intact organism or its progeny, secondary to changes in endocrine function. Endocrine disruptors of widely diverse chemical structures that have oestrogenic properties are known as oestrogenic xenobiotics or xenoestrogens. Some of these substances, such as phytoestrogens and mycoestrogens, can come from diet or from the environment. Although the oestrogenic activity of these substances is weaker than that of oestradiol, new chemicals with endocrine disrupting potential continue to be discovered, inadvertent forms of exposure are constantly being identified, and there is increasing concern about cumulative effects. Studies in the 1960s and 1970s characterized the oestrogenicity of a number of industrial compounds and the pesticides o,p-DDT, kepone, methoxychlor, phenolic derivatives and polychlorinated biphenyls (PCBs). In the last 5 years, several environmental chemicals have been added to the list of xenoestrogens, including the pesticides toxaphene, dieldrin and endosulphan, and several different compounds used in the food industry, antioxidants such a t-butylhydroxyanisole; plasticizers such as benzylbutylphthalate and 4-OH-alkylphenols; and substances used in dental restorations, such as bisphenol-A. The relevance of these newly discovered endocrine disruptors to human health is now starting to emerge. The few studies that have investigated their effect in humans point in the same direction: if there is indeed an association between exposure to substances with hormone-disruptive activity and certain disorders of endocrine organs, the incidence of such disorders would be greater in areas where exposure to agents with this activity is high. A closer scrutiny is required to determine whether these newly discovered endocrine disrupting chemicals contribute, together with oestrogenic pesticides, to the exposure of humans to xenoestrogens.",
"title": "Inadvertent exposure to xenoestrogens."
},
{
"docid": "MED-2655",
"text": "Background Broad dietary patterns have been linked to asthma but the relative contribution of specific nutrients is unclear. Soy genistein has important anti-inflammatory and other biological effects that might be beneficial in asthma. A positive association was previously reported between soy genistein intake and lung function but not with asthma exacerbations. Aims To conduct a post-hoc analysis of patients with inadequately controlled asthma enrolled in a prospective multicentre clinical trial to replicate this association. Methods A total of 300 study participants were included in the analysis. Dietary soy genistein intake was measured using the Block Soy Foods Screener. The level of soy genistein intake (little or no intake, moderate intake, or high intake) was compared with baseline lung function (pre-bronchodilator forced expiratory volume in 1 second (FEV1)) and asthma control (proportion of participants with an episode of poor asthma control (EPAC) and annualised rates of EPACs over a 6-month follow-up period. Results Participants with little or no genistein intake had a lower baseline FEV1 than those with a moderate or high intake (2.26L vs. 2.53L and 2.47L, respectively; p=0.01). EPACs were more common among those with no genistein intake than in those with a moderate or high intake (54% vs. 35% vs. 40%, respectively; p<0.001). These findings remained significant after adjustment for patient demographics and body mass index. Conclusions In patients with asthma, consumption of a diet with moderate to high amounts of soy genistein is associated with better lung function and better asthma control.",
"title": "Association of dietary soy genistein intake with lung function and asthma control: a post-hoc analysis of patients enrolled in a prospective multicentre clinical trial"
},
{
"docid": "MED-1002",
"text": "Prenatal exposure to polybrominated diphenyl ethers (PBDEs) may disrupt thyroid function and contribute to adverse neurodevelopmental outcomes. We conducted a pilot study to explore the relationship between serum concentrations of lower-brominated PBDEs (BDE-17 to -154), higher-brominated PBDEs (BDE-183 to -209), and hydroxylated PBDE metabolites (OH-PBDEs) with measures of thyroid function in pregnant women. Concentrations of PBDEs, OH-PBDEs, thyroid-stimulating hormone (TSH), total thyroxine (T4), and free T4 were measured in serum samples collected between 2008 and 2009 from 25 second trimester pregnant women in California. Median concentrations of lower-brominated PBDEs and OH-PBDEs were the highest reported to date in pregnant women. Median concentrations of BDE-47 and the sum of lower-brominated PBDEs (ΣPBDE5) were 43.1 ng/g lipid and 85.8 ng/g lipid; and 0.084 ng/mL for the sum of OH-PBDEs (ΣOH-PBDE4). We observed a positive association between the weighted sum of chemicals known to bind to transthyretin (ΣTTR binders) and TSH levels. We also found positive associations between TSH and ΣPBDE5, ΣOH-PBDE4, BDE-47, BDE-85, 5-OH-BDE47, and 4′-OH-BDE49; and an inverse association with BDE-207. Relationships with free and total T4 were weak and inconsistent. Our results indicate that PBDE exposures are elevated in pregnant women in California, and suggest a relationship with thyroid function. Further investigation is warranted to characterize the risks of PBDE exposures during pregnancy.",
"title": "Polybrominated diphenyl ethers (PBDEs), hydroxylated PBDEs (OH-PBDEs), and measures of thyroid function in second trimester pregnant women in California"
},
{
"docid": "MED-4175",
"text": "In this study, 10 perfluorochemicals (PFCs) were measured in meat, meat products, and eggs, and in indoor dust, collected in China. Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) were the most frequently detected PFCs in these samples. Mean concentrations of PFOS and PFOA in foodstuffs were in the range of 0.05-1.99 ng/g fresh wt and 0.06-12.5 ng/g fresh wt, respectively. The mean concentrations of PFOA, perfluoroheptanoic acid (PFHpA), and PFOS in indoor dust were 205, 14.0, and 4.86 ng/g, dry wt, respectively. The estimated daily intake of PFOS and PFOA from meat, meat products and eggs (EDI(meat&eggs)) ranged from 6.00 to 9.64 ng/d and from 254 to 576 ng/d, respectively, when the values below the limit of quantitation (LOQ) were assigned as 0, and from 8.80 to 15.0 ng/d and from 255 to 577 ng/d, respectively, when the values below the LOQ were set at 1/2LOQ. The EDI(meat&eggs) of PFOS and PFOA increased with increasing family income. The estimated daily intake of PFOS and PFOA through inhalation of dust (EDI(dust)) ranged from 0.23 to 0.31 ng/d and from 9.68 to 13.4 ng/d, respectively. The daily intakes of PFOS and PFOA from the consumption of meat, meat products, and eggs, and from dust ingestion, as calculated from our samples in this study, were compared with estimated daily intake of PFCs reported from the concentrations in drinking water, fish and seafood from China. Our calculations indicate that dietary sources (EDI(dietary)) account for the overwhelming proportion of (>99% for PFOS and 98% for PFOA) total daily intake (TDI) in adults. The analyzed foodstuffs (meat, meat products, and eggs) were not the major contributors to dietary exposure to PFOS, whereas, meat was the primary contributor to dietary exposure to PFOA.",
"title": "Perfluorochemicals in meat, eggs and indoor dust in China: assessment of sources and pathways of human exposure to perfluorochemicals."
},
{
"docid": "MED-998",
"text": "Background: There is increasing interest in the potential effects of polybrominated diphenyl ethers (PBDEs) on children’s neuropsychological development, but only a few small studies have evaluated such effects. Objectives: Our goal was to examine the association between PBDE concentrations in colostrum and infant neuropsychological development and to assess the influence of other persistent organic pollutants (POPs) on such association. Methods: We measured concentrations of PBDEs and other POPs in colostrum samples of 290 women recruited in a Spanish birth cohort. We tested children for mental and psychomotor development with the Bayley Scales of Infant Development at 12–18 months of age. We analyzed the sum of the seven most common PBDE congeners (BDEs 47, 99, 100, 153, 154, 183, 209) and each congener separately. Results: Increasing Σ7PBDEs concentrations showed an association of borderline statistical significance with decreasing mental development scores (β per log ng/g lipid = –2.25; 95% CI: –4.75, 0.26). BDE-209, the congener present in highest concentrations, appeared to be the main congener responsible for this association (β = –2.40, 95% CI: –4.79, –0.01). There was little evidence for an association with psychomotor development. After adjustment for other POPs, the BDE-209 association with mental development score became slightly weaker (β = –2.10, 95% CI: –4.66, 0.46). Conclusions: Our findings suggest an association between increasing PBDE concentrations in colostrum and a worse infant mental development, particularly for BDE-209, but require confirmation in larger studies. The association, if causal, may be due to unmeasured BDE-209 metabolites, including OH-PBDEs (hydroxylated PBDEs), which are more toxic, more stable, and more likely to cross the placenta and to easily reach the brain than BDE-209.",
"title": "Polybrominated Diphenyl Ethers (PBDEs) in Breast Milk and Neuropsychological Development in Infants"
},
{
"docid": "MED-1098",
"text": "The first U.S. nationwide food sampling with measurement of dioxins, dibenzofurans, and coplanar, mono-ortho and di-ortho polychlorinated biphenyls (PCBs) is reported in this study. Twelve separate analyses were conducted on 110 food samples divided into pooled lots by category. The samples were purchased in 1995 in supermarkets in Atlanta, GA, Binghamton, NY, Chicago, IL, Louisville, KY, and San Diego, CA. Human milk also was collected to estimate nursing infants' consumption. The food category with highest World Health Organization (WHO) dioxin toxic equivalent (TEQ) concentration was farm-grown freshwater fish fillet with 1.7 pg/g, or parts per trillion (ppt), wet, or whole, weight. The category with the lowest TEQ level was a simulated vegandiet, with 0.09 ppt. TEQ concentrations in ocean fish, beef, chicken, pork, sandwich meat, eggs, cheese, and ice cream, as well as human milk, were in the range O.33 to 0.51 ppt, wet weight. In whole dairy milk TEQ was 0.16 ppt, and in butter 1.1 ppt. Mean daily intake of TEQ for U.S. breast-fed infants during the first year of life was estimated at 42 pg/kg body weight. For children aged 1-11 yr the estimated daily TEQ intake was 6.2 pg/kg body weight. For males and females aged 12-19 yr, the estimated TEQ intake was 3.5 and 2.7 pg/kg body weight, respectively. For adult men and women aged 20-79 yr, estimated mean daily TEQ intakes were 2.4 and 2.2 pg/kg body weight, respectively. Estimated mean daily intake of TEQ declined with age to a low of 1.9 pg/kg body weight at age 80 yr and older. For all ages except 80 yr and over, estimates were higher for males than females. For adults, dioxins, dibenzofurans, and PCBs contributed 42%, 30%, and 28% of dietary TEQ intake, respectively. DDE was also analyzed in the pooled food samples.",
"title": "Intake of dioxins and related compounds from food in the U.S. population."
},
{
"docid": "MED-2651",
"text": "The aims of this study were to determine the concentrations of 4-nonylphenol (NP) and 4-octylphenol (OP) in 59 human milk samples and to examine related factors including mothers' demographics and dietary habits. Women who consumed over the median amount of cooking oil had significantly higher OP concentrations (0.98 ng/g) than those who consumed less (0.39 ng/g) (P < 0.05). OP concentration was significantly associated with the consumption of cooking oil (beta = 0.62, P < 0.01) and fish oil capsules (beta = 0.39, P < 0.01) after adjustment for age and body mass index (BMI). NP concentration was also significantly associated with the consumption of fish oil capsules (beta = 0.38, P < 0.01) and processed fish products (beta = 0.59, P < 0.01). The food pattern of cooking oil and processed meat products from factor analysis was strongly associated with OP concentration in human milk (P < 0.05). These determinations should aid in suggesting foods for consumption by nursing mothers in order to protect their infants from NP/OP exposure. 2010 Elsevier Ltd. All rights reserved.",
"title": "Alkylphenols in human milk and their relations to dietary habits in central Taiwan."
},
{
"docid": "MED-2660",
"text": "BACKGROUND: Rapid socioeconomic development in Japan since the beginning of the Seven Countries Study in 1958 has brought remarkable changes in lifestyle and dietary patterns. We investigated the relationship between time trends in nutrient intake and serum cholesterol levels in a Japanese cohort of the Seven Countries Study, in Tanushimaru, a typical farming town on Kyushu Island. METHODS: Subjects totaled 628 in 1958, 539 in 1977, 602 in 1982, 752 in 1989, and 402 in 1999, and all of the subjects were men aged 40-64 years. Eating patterns were evaluated by 24-hour dietary recall from 1958 through 1989, and by a food frequency questionnaire in 1999. We also measured serum cholesterol levels in each health examination. RESULTS: The total daily energy intake decreased from 2837 kcal in 1958 to 2202 kcal in 1999. The carbohydrate intake in percentage of total daily energy intake decreased markedly, from 84% in 1958 to 62% in 1999, in contrast to large increases during this period in protein intake (from 11% to 18%) and fat intake (from 5% to 20%). In proportion to the dramatic change in protein and fat intake, serum cholesterol levels showed large increases (from 152.5mg/dl to 194.2 mg/ dL). CONCLUSIONS: In spite of such big dietary changes toward a westernized diet, the incidence of coronary artery disease in a rural Japanese area remains low. However, careful surveillance is needed in the future because of the remarkably increasing intake of fats, especially saturated fatty acids.",
"title": "Trends in nutritional intake and serum cholesterol levels over 40 years in Tanushimaru, Japanese men."
},
{
"docid": "MED-4176",
"text": "Perfluorooctanesulfonylfluoride (POSF)-based compounds have been manufactured and used in a variety of industrial applications. These compounds degrade to perfluorooctanesulfonate (PFOS) which is regarded as a persistent end-stage metabolite and is found to accumulate in tissues of humans and wildlife. PFOS, perfluorohexanesulfonate (PFHxS), perfluorooctanoate (PFOA), and perfluorooctanesulfonamide (PFOSA) have been found in human sera from the United States. In this study, concentrations of PFHxS, perfluorobutanesulfonate (PFBS), PFOS, perfluorohexanoic acid (PFHxA), PFOA, perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorododecanoic acid (PFDoDA), and PFOSA were measured in 85 samples of whole human blood collected from nine cities (eight provinces) in China, including Shenyang (Liaoning), Beijing (Hebei), Zhengzhou (Henan), Jintan (Jiangsu), Wuhan (Hubei), Zhoushan (Zhejiang), Guiyang (Guizhou), Xiamen (Fujian), and Fuzhou (Fujian). Among the 10 perfluorinated compounds (PFCs) measured, PFOS was the predominant compound. The mean concentration of PFOS was greatest in samples collected from Shenyang (79.2 ng/mL) and least in samples from Jintan (3.72 ng/mL). PFHxS was the next most abundant perfluorochemical in the samples. No age-related differences in the concentrations of PFOA, PFOS, PFOSA, and PFHxS were observed. Gender-related differences were found,with males higher for PFOS and PFHxS, and females higher in PFUnDA. Concentrations of PFHxS were positively correlated with those of PFOS, while concentrations of PFNA, PFDA, and PFUnDA were positively correlated with those of PFOA. There were differences in the concentration profiles (percentage composition) of various PFCs in the samples among the nine cities.",
"title": "Perfluorooctanesulfonate and related fluorochemicals in human blood samples from China."
},
{
"docid": "MED-4177",
"text": "Fifty-six seasonal snowpack samples were collected at remote alpine, sub-arctic, and arctic sites in eight Western US national parks during three consecutive years (2003–2005). Four current-use pesticides (CUPs) (dacthal (DCPA), chlorpyrifos, endosulfan, and γ-hexachlorocyclohexane (HCH)) and four historic-use pesticides (HUPs) (dieldrin, α-HCH, chlordane, and hexachlorobenzene (HCB)) were commonly measured at all sites, during all years. The mean coefficient of variation for pesticide concentrations was 15% for site replicate samples, 41% for intra-park replicate samples, and 59% for inter-annual replicate samples. The relative pesticide concentration profiles were consistent from year to year but unique for individual parks, indicating a regional source effect. HUP concentrations were well-correlated with regional cropland intensity when the effect of temperature on snow-air partitioning was considered. The mass of individual CUPs used in regions located one-day upwind of the parks was calculated using air mass back trajectories and this was used to explain the distribution of CUPs among the parks. The percent of the snowpack pesticide concentration due to regional transport was high (>75%) for the majority of pesticides in all parks. These results suggest that the majority of pesticide contamination in US national parks is due to pesticide use in North America.",
"title": "Variability in Pesticide Deposition and Source Contributions to Snowpack in Western US National Parks"
},
{
"docid": "MED-2654",
"text": "4-Nonylphenols (NPs) are common products of biodegradation of a widely used group of nonionic surfactants, the nonylphenol ethoxylates (NPEs). These compounds are known to be persistent, toxic, and estrogen active. There is a worldwide scientific and public discussion on the potential consequences of human long term dietary exposure to such endocrine disrupters. Despite numerous determinations of NPs in environmental samples no systematical reports exist relating to concentrations of NPs in food. We analyzed NPs in 60 different foodstuff commercially available in Germany. The results indicate that NPs are ubiquitous in food. The concentrations of NPs on a fresh weight basis varied between 0.1 and 19.4 microg/kg regardless of the fat content of the foodstuff. Based on data on German food consumption rates and these first analyses of NPs in food, the daily intake for an adult was calculated to be 7.5 microg/day NPs. For infants exclusively fed with breast milk or infant formulas daily intakes of 0.2 microg/day and 1.4 microg/day NPs, respectively, can be estimated.",
"title": "Endocrine disrupting nonylphenols are ubiquitous in food."
},
{
"docid": "MED-2643",
"text": "The incidence and/or prevalence of health problems associated with endocrine-disruption have increased. Many chemicals have endocrine-disrupting properties, including bisphenol A, some organochlorines, polybrominated flame retardants, perfluorinated substances, alkylphenols, phthalates, pesticides, polycyclic aromatic hydrocarbons, alkylphenols, solvents, and some household products including some cleaning products, air fresheners, hair dyes, cosmetics, and sunscreens. Even some metals were shown to have endocrine-disrupting properties. Many observations suggesting that endocrine disruptors do contribute to cancer, diabetes, obesity, the metabolic syndrome, and infertility are listed in this paper. An overview is presented of mechanisms contributing to endocrine disruption. Endocrine disruptors can act through classical nuclear receptors, but also through estrogen-related receptors, membrane-bound estrogen-receptors, and interaction with targets in the cytosol resulting in activation of the Src/Ras/Erk pathway or modulation of nitric oxide. In addition, changes in metabolism of endogenous hormones, cross-talk between genomic and nongenomic pathways, cross talk with estrogen receptors after binding on other receptors, interference with feedback regulation and neuroendocrine cells, changes in DNA methylation or histone modifications, and genomic instability by interference with the spindle figure can play a role. Also it was found that effects of receptor activation can differ in function of the ligand.",
"title": "Endocrine-Disrupting Chemicals: Associated Disorders and Mechanisms of Action"
},
{
"docid": "MED-1000",
"text": "Background Animal and in vitro studies demonstrated a neurotoxic potential of brominated flame retardants, a group of chemicals used in many household and commercial products to prevent fire. Although the first reports of detrimental neurobehavioral effects in rodents appeared more than ten years ago, human data are sparse. Methods As a part of a biomonitoring program for environmental health surveillance in Flanders, Belgium, we assessed the neurobehavioral function with the Neurobehavioral Evaluation System (NES-3), and collected blood samples in a group of high school students. Cross-sectional data on 515 adolescents (13.6-17 years of age) was available for the analysis. Multiple regression models accounting for potential confounders were used to investigate the associations between biomarkers of internal exposure to brominated flame retardants [serum levels of polybrominated diphenyl ether (PBDE) congeners 47, 99, 100, 153, 209, hexabromocyclododecane (HBCD), and tetrabromobisphenol A (TBBPA)] and cognitive performance. In addition, we investigated the association between brominated flame retardants and serum levels of FT3, FT4, and TSH. Results A two-fold increase of the sum of serum PBDE’s was associated with a decrease of the number of taps with the preferred-hand in the Finger Tapping test by 5.31 (95% CI: 0.56 to 10.05, p = 0.029). The effects of the individual PBDE congeners on the motor speed were consistent. Serum levels above the level of quantification were associated with an average decrease of FT3 level by 0.18 pg/mL (95% CI: 0.03 to 0.34, p = 0.020) for PBDE-99 and by 0.15 pg/mL (95% CI: 0.004 to 0.29, p = 0.045) for PBDE-100, compared with concentrations below the level of quantification. PBDE-47 level above the level of quantification was associated with an average increase of TSH levels by 10.1% (95% CI: 0.8% to 20.2%, p = 0.033), compared with concentrations below the level of quantification. We did not observe effects of PBDE’s on neurobehavioral domains other than the motor function. HBCD and TBBPA did not show consistent associations with performance in the neurobehavioral tests. Conclusions This study is one of few studies and so far the largest one investigating the neurobehavioral effects of brominated flame retardants in humans. Consistently with experimental animal data, PBDE exposure was associated with changes in the motor function and the serum levels of the thyroid hormones.",
"title": "Neurobehavioral function and low-level exposure to brominated flame retardants in adolescents: a cross-sectional study"
},
{
"docid": "MED-2659",
"text": "U.S. and European regulators and researchers disagree over risks of a common class of surfactants.",
"title": "European bans on surfactant trigger transatlantic debate."
},
{
"docid": "MED-999",
"text": "Polybrominated diphenyl ethers (PBDEs) are a class of brominated flame retardants (BFRs) used to protect people from fires by reducing the flammability of combustible materials. In recent years, PBDEs have become widespread environmental pollutants, while body burden in the general population has been increasing. A number of studies have shown that, as for other persistent organic pollutants, dietary intake is one of the main routes of human exposure to PBDEs. The most recent scientific literature concerning the levels of PBDEs in foodstuffs and the human dietary exposure to these BFRs are here reviewed. It has been noted that the available information on human total daily intake through food consumption is basically limited to a number of European countries, USA, China, and Japan. In spite of the considerable methodological differences among studies, the results show notable coincidences such as the important contribution to the sum of total PBDEs of some congeners such as BDEs 47, 49, 99 and 209, the comparatively high contribution of fish and seafood, and dairy products, and the probably limited human health risks derived from dietary exposure to PBDEs. Various issues directly related to human exposure to PBDEs through the diet still need investigation. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Polybrominated diphenyl ethers in food and human dietary exposure: a review of the recent scientific literature."
},
{
"docid": "MED-3959",
"text": "Context: Earlier age at menarche is associated with rapid infancy weight gain and childhood obesity. The role of hormone levels in mediating these associations is unclear. Objective: The aim of this study was to identify childhood hormone levels at age 8 yr that are associated with early menarche, independent of body size. Design, Settings, and Subjects: A total of 329 girls from a prospective United Kingdom birth cohort study provided blood samples at mean age 8.1 yr (range, 8.0–8.5) for hormone measurements and were followed longitudinally to establish age at menarche. Main Outcome Measures: Fasting plasma levels of IGF-I, androstenedione, dehydroepiandrosterone sulfate (DHEAS), leptin, insulin, IGF binding protein-1, and SHBG were measured. Age at menarche was reported by questionnaire and categorized as before 12.0, 12.0–13.0, or later than 13 yr. Results: Earlier menarche was associated with greater body weight, height, and body mass index at age 8 yr (all P-trend <0.001). Before adjustment for body size, earlier menarche was associated with higher levels of IGF-I, androstenedione, DHEAS, leptin, and fasting insulin, and with lower levels of IGF binding protein-1 and SHBG at age 8 yr (all P < 0.01). After adjustment for body mass index and height at age 8 yr, only IGF-I (P = 0.004), androstenedione (P = 0.01), and DHEAS (P = 0.01) remained associated with earlier menarche. Conclusions: Associations between higher levels of IGF-I and adrenal androgens at age 8 yr with earlier menarche, independent of body size, support functional roles of these hormones in regulating puberty timing in girls. Higher levels of these hormones reported in children who exhibited rapid weight gain during infancy may indicate their role in developmental pathways leading to earlier sexual maturation.",
"title": "Higher Levels of IGF-I and Adrenal Androgens at Age 8 Years Are Associated with Earlier Age at Menarche in Girls"
},
{
"docid": "MED-2627",
"text": "Human exposure to endocrine disrupters (EDs) is widespread and is considered to pose a growing threat to human health. Recent advances in molecular and genetic research and better understanding of mechanisms of blastic cell transformation have led to efforts to improve cancer risk assessment for populations exposed to this family of xenobiotics. In risk assessment, low dose extrapolation of cancer incidence data from both experimental animals and epidemiology studies has been largely based on models assuming linear correlation at low doses, despite existence of evidence showing otherwise. Another weakness of ED risk assessment is poor exposure data in ecological studies. Those are frequently rough estimates derived from contaminated items of local food basket surveys. Polyhalogenated hydrocarbons are treated as examples. There is growing sense of urgency to develop a biologically based dose response model of cancer risk, integrating emerging data from molecular biology and epidemiology to provide more realistic data for risk assessors, public, public health managers and environmental issues administrators.",
"title": "Human exposure to endocrine disrupters: carcinogenic risk assessment."
},
{
"docid": "MED-2657",
"text": "BACKGROUND: Japanese cedar pollinosis, caused by the pollen of the Japanese cedar tree (Cryptomeria japonica), is the commonest seasonal allergic disease in Japan. A number of epidemiological surveys have been reported on Japanese cedar pollinosis, but it has never been assessed systematically or quantitatively. To confirm the increasing prevalence of Japanese cedar pollinosis and related factors, we conducted a meta-regression analysis on population-based surveys in Japan. METHODS: We searched for data from population-based surveys in which serological methods were used to test all participants. Weighted regression of logit-transformed prevalence and sensitization rates were used to evaluate the effects of the year of survey, age, and degree of urbanization. We also analyzed the relationship between prevalence and sensitization rate. RESULTS: Thirty-eight reports with 27 subgroups for prevalence and 134 subgroups for sensitization rate were selected from the literature published in the years between 1986 and 2000. The Japanese cedar pollen sensitization rate was found to be significantly correlated with the year of survey, age, and degree of urbanization (adjusted R(2) = 0.55). The coefficient for the correlation between the prevalence and the sensitization rate revealed a statistically significant correlation (Pearson's r = 0.70, p < 0.001). CONCLUSIONS: The prevalence of Japanese cedar pollinosis among adolescents was predicted to be 28.7% in metropolitan areas and 24.5% in the general population in urban areas in the year 2004, derived from the estimated sensitization rate and the relationship between sensitization rate and prevalence. The prevalence of Japanese cedar pollinosis increased 2.6-fold between 1980 and 2000, and the prevalence differed considerably according to age and degree of urbanization. Copyright (c) 2005 S. Karger AG, Basel",
"title": "Increasing prevalence of Japanese cedar pollinosis: a meta-regression analysis."
},
{
"docid": "MED-2649",
"text": "Background Dietary fat exerts numerous complex effects on proinflammatory and immunologic pathways. Several epidemiological studies have examined the relationships between intake of fatty acids and/or foods high in fat and allergic rhinitis, but have provided conflicting findings. The current cross-sectional study investigated such relationships in Japan. Methods Study subjects were 1745 pregnant women. The definition of rhinoconjunctivitis was based on criteria from the International Study of Asthma and Allergies in Childhood. Information on dietary factors was collected using a validated self-administered diet history questionnaire. Adjustment was made for age; gestation; region of residence; number of older siblings; number of children; smoking; secondhand smoke exposure at home and at work; family history of asthma, atopic eczema, and allergic rhinitis; household income; education; and body mass index. Results The prevalence of rhinoconjunctivitis in the past 12 months was 25.9%. Higher meat intake was significantly associated with an increased prevalence of rhinoconjunctivitis: the adjusted odds ratio between extreme quartiles was 1.71 (95% confidence interval: 1.25-2.35, P for trend = 0.002). No measurable association was found between fish intake and rhinoconjunctivitis. Intake of total fat, saturated fatty acids, monounsaturated fatty acids, n-3 polyunsaturated fatty acids, α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, n-6 polyunsaturated fatty acids, linoleic acid, arachidonic acid, and cholesterol and the ratio of n-3 to n-6 polyunsaturated fatty acid intake were not evidently related to the prevalence of rhinoconjunctivitis. Conclusions The current results suggest that meat intake may be positively associated with the prevalence of rhinoconjunctivitis in young adult Japanese women.",
"title": "Dietary meat and fat intake and prevalence of rhinoconjunctivitis in pregnant Japanese women: baseline data from the Kyushu Okinawa Maternal and Child Health Study"
},
{
"docid": "MED-996",
"text": "Polybrominated diphenyl ethers (PBDEs) are persistent organic chemicals used as flame retardants in textiles, plastics, and consumer products. Although PBDE accumulation in humans has been noted since the 1970s, few studies have investigated PBDEs within the gestational compartment, and none to date has identified levels in amniotic fluid. The present study reports congener-specific brominated diphenyl ether (BDE) concentrations in second-trimester clinical amniotic fluid samples collected in 2009 from fifteen women in southeast Michigan, USA. Twenty-one BDE congeners were measured by GC/MS/NCI. The average total PBDE concentration was 3795 pg/ml amniotic fluid (range: 337 – 21842 pg/ml). BDE-47 and BDE-99 were identified in all samples. Based on median concentrations, the dominant congeners were BDE-208, 209, 203, 206, 207, and 47 representing 23, 16, 12, 10, 9 and 6%, respectively, of the total detected PBDEs. PBDE concentrations were identified in all amniotic fluid samples from southeast Michigan, supporting a need for further investigations of fetal exposure pathways and potential impacts on perinatal health.",
"title": "Concentrations and speciation of polybrominated diphenyl ethers in human amniotic fluid"
},
{
"docid": "MED-1003",
"text": "background: California children’s exposures to polybrominated diphenyl ether flame retardants (PBDEs) are among the highest worldwide. PBDEs are known endocrine disruptors and neurotoxicants in animals. Objective: Here we investigate the relation of in utero and child PBDE exposure to neurobehavioral development among participants in CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas), a California birth cohort. Methods: We measured PBDEs in maternal prenatal and child serum samples and examined the association of PBDE concentrations with children’s attention, motor functioning, and cognition at 5 (n = 310) and 7 years of age (n = 323). Results: Maternal prenatal PBDE concentrations were associated with impaired attention as measured by a continuous performance task at 5 years and maternal report at 5 and 7 years of age, with poorer fine motor coordination—particularly in the nondominant—at both age points, and with decrements in Verbal and Full-Scale IQ at 7 years. PBDE concentrations in children 7 years of age were significantly or marginally associated with concurrent teacher reports of attention problems and decrements in Processing Speed, Perceptual Reasoning, Verbal Comprehension, and Full-Scale IQ. These associations were not altered by adjustment for birth weight, gestational age, or maternal thyroid hormone levels. Conclusions: Both prenatal and childhood PBDE exposures were associated with poorer attention, fine motor coordination, and cognition in the CHAMACOS cohort of school-age children. This study, the largest to date, contributes to growing evidence suggesting that PBDEs have adverse impacts on child neurobehavioral development.",
"title": "In Utero and Childhood Polybrominated Diphenyl Ether (PBDE) Exposures and Neurodevelopment in the CHAMACOS Study"
},
{
"docid": "MED-2646",
"text": "BACKGROUND: Certain foods may increase or decrease the risk of developing asthma, rhinoconjunctivitis and eczema. We explored the impact of the intake of types of food on these diseases in Phase Three of the International Study of Asthma and Allergies in Childhood. METHODS: Written questionnaires on the symptom prevalence of asthma, rhinoconjunctivitis and eczema and types and frequency of food intake over the past 12 months were completed by 13-14-year-old adolescents and by the parents/guardians of 6-7-year-old children. Prevalence ORs were estimated using logistic regression, adjusting for confounders, and using a random (mixed) effects model. RESULTS: For adolescents and children, a potential protective effect on severe asthma was associated with consumption of fruit ≥3 times per week (OR 0.89, 95% CI 0.82 to 0.97; OR 0.86, 95% CI 0.76 to 0.97, respectively). An increased risk of severe asthma in adolescents and children was associated with the consumption of fast food ≥3 times per week (OR 1.39, 95% CI 1.30 to 1.49; OR 1.27, 95% CI 1.13 to 1.42, respectively), as well as an increased risk of severe rhinoconjunctivitis and severe eczema. Similar patterns for both ages were observed for regional analyses, and were consistent with gender and affluence categories and with current symptoms of all three conditions. CONCLUSIONS: If the association between fast foods and the symptom prevalence of asthma, rhinoconjunctivitis and eczema is causal, then the findings have major public health significance owing to the rising consumption of fast foods globally.",
"title": "Do fast foods cause asthma, rhinoconjunctivitis and eczema? Global findings from the International Study of Asthma and Allergies in Childhood (ISAA..."
},
{
"docid": "MED-2647",
"text": "Continuing evidence of the feminising effects of xenoestrogens on a range of wildlife species increases the need to assess the human health risk of these estrogen mimics. We have estimated the exposure of New Zealand males, females and young men to a range of naturally occurring and synthetic xenoestrogens found in food. Only estrogenic compounds that act by interaction with the estrogen receptor have been included. Theoretical plasma estrogen activity levels were derived from estrogen exposure estimates and estrogenic potency data. Theoretical plasma levels were compared with published data for specific xenoestrogens. There was surprisingly close agreement. Xenoestrogenicity from dietary intake was almost equally attributed to naturally occurring and synthetic xenoestrogens. Relative contributions for a male, for example were isoflavones (genistein and daidzein) (36%) and bisphenol A (34%) with smaller contributions from alkyl phenols (18%) and the flavonoids (phloretin and kaempferol) (12%). It is suggested that dietary xenoestrogens might have a pharmacological effect on New Zealand males and postmenopausal women, but are unlikely to be significant for pre-menopausal women.",
"title": "Dietary exposure to xenoestrogens in New Zealand."
},
{
"docid": "MED-2661",
"text": "This paper presents the results of an investigation on the occurrence of alkylphenols (APs) and their ethoxylates (APEs) in 8 edible marine species from the Adriatic Sea and tries to estimate the corresponding intake for the Italian population. Two crustaceans, Nephrops norvegicus (Norway lobster) and Squilla mantis (spottail mantis shrimp), plus six fish species, Engraulis enchrascicolus (anchovy), Scomber scombrus (Atlantic mackerel), Merluccius merluccius (European hake), Mullus barbatus (red mullet), Solea vulgaris (common sole) and Lophius piscatorius (angler) were analyzed for their content of nonylphenol (NP), octylphenol (OP) and octylphenol polyethoxylates (OPEs). These compounds were found in all analysed samples. NP was detected at the highest concentrations: 118-399 and 9.5-1431 ng g(-1) fresh weight (fw) respectively in crustaceans and fish. OP was found at respective levels of 2.7-4.7 and 0.3-3.8 ng g(-1) fw in crustaceans and fish, whereas OPE was determined at respective concentrations of 1.2-16.8 and 0.2-21.1 ng g(-1) fw in the same species. These results, together with those from a previous study on 4 edible mollusc, allow to estimate respective daily intakes for NP, OP, and OPE of about 12, 0.1, and 0.1 microg day(-1) for an Italian adult living along the Adriatic Coast. In relation to NP and OP, these intakes are much lower than the doses associated with toxic effects in laboratory animals (9 mg kg(-1) bw for rats). Nevertheless, data of exposure from other sources to these chemicals and others with similar biological characteristics are needed.",
"title": "Alkylphenols and alkylphenol ethoxylates contamination of crustaceans and fishes from the Adriatic Sea (Italy)."
},
{
"docid": "MED-4179",
"text": "Rainfall samples were collected during the 2003 and 2004 growing seasons at four agricultural locales across the USA in Maryland, Indiana, Nebraska, and California. The samples were analyzed for 21 insecticides, 18 herbicides, three fungicides, and 40 pesticide degradates. Data from all sites combined show that 7 of the 10 most frequently detected pesticides were herbicides, with atrazine (70%) and metolachlor (83%) detected at every site. Dacthal, acetochlor, simazine, alachlor, and pendimethalin were detected in more than 50% of the samples. Chlorpyrifos, carbaryl, and diazinon were the only insecticides among the 10 most frequently detected compounds. Of the remaining pesticide parent compounds, 18 were detected in fewer than 30% of the samples, and 13 were not detected. The most frequently detected degradates were deethylatrazine; the oxygen analogs (OAs) of the organophosphorus insecticides chlorpyrifos, diazinon, and malathion; and 1-napthol (degradate of carbaryl). Deethylatrazine was detected in nearly 70% of the samples collected in Maryland, Indiana, and Nebraska but was detected only once in California. The OAs of chlorpyrifos and diazinon were detected primarily in California. Degradates of the acetanilide herbicides were rarely detected in rain, indicating that they are not formed in the atmosphere or readily volatilized from soils. Herbicides accounted for 91 to 98% of the total pesticide mass deposited by rain except in California, where insecticides accounted for 61% in 2004. The mass of pesticides deposited by rainfall was estimated to be less than 2% of the total applied in these agricultural areas.",
"title": "Pesticides in rain in four agricultural watersheds in the United States."
},
{
"docid": "MED-4728",
"text": "Over the last two decades, the incidence of obesity and associated metabolic syndrome diseases has risen dramatically, becoming a global health crisis. Increased caloric intake and decreased physical activity are believed to represent the root causes of this dramatic rise. However, recent findings highlight the possible involvement of environmental obesogens, xenobiotic chemicals that can disrupt the normal developmental and homeostatic controls over adipogenesis and energy balance. Environmental estrogens, i.e. chemicals with estrogenic potential, have been reported to perturb adipogenic mechanisms using in vitro model systems, but other classes of endocrine-disrupting chemicals are now coming under scrutiny as well. Organotins represent one class of widespread persistent organic pollutants with potent endocrine-disrupting properties in both invertebrates and vertebrates. New data identify tributyltin chloride and triphenyltin chloride as nanomolar agonist ligands for retinoid X receptor (RXR alpha, RXR beta, and RXR gamma) and peroxisome proliferator-activated receptor gamma, nuclear receptors that play pivotal roles in lipid homeostasis and adipogenesis. The environmental obesogen hypothesis predicts that inappropriate receptor activation by organotins will lead directly to adipocyte differentiation and a predisposition to obesity and/or will sensitize exposed individuals to obesity and related metabolic disorders under the influence of the typical high-calorie, high-fat Western diet. The linking of organotin exposure to adipocyte differentiation and obesity opens an important new area of research into potential environmental influences on human health and disease.",
"title": "Environmental obesogens: organotins and endocrine disruption via nuclear receptor signaling."
},
{
"docid": "MED-3955",
"text": "BACKGROUND Polybrominated Diphenyl Ethers (PBDEs), widely used as flame retardants since the 1970s, have exhibited endocrine disruption in experimental studies. Tetra- to hexa-BDE congeners are estrogenic, while hepta-BDE and 6-OH-BDE-47 are antiestrogenic. Most PBDEs also have antiandrogenic activity. It is not clear, however, whether PBDEs affect human reproduction. OBJECTIVES The analysis was designed to investigate the potential endocrine disruption of PBDEs on the age at menarche in adolescent girls. METHODS We analyzed the data from a sample of 271 adolescent girls (age 12–19 years) in the National Health and Nutrition Examination Survey (NHANES), 2003–2004. We estimated the associations between individual and total serum BDEs (BDE-28, -47, -99, -100, -153, and -154, lipid adjusted) and mean age at menarche. We also calculated the risk ratios (RRs) and 95% confidence intervals (CI) for menarche prior to age 12 years in relation to PBDE exposure. RESULTS The median total serum BDE concentration was 44.7 ng/g lipid. Higher serum PBDE concentrations were associated with slightly earlier ages at menarche. Each natural log unit of total BDEs was related to a change of −0.10 (95% CI: −0.33, 0.13) years of age at menarche and a RR of 1.60 (95% CI: 1.12, 2.28) for experiencing menarche before 12 years of age, after adjustment for potential confounders. CONCLUSION These data suggest high concentrations of serum PBDEs during adolescence are associated with a younger age of menarche.",
"title": "Serum PBDEs and Age at Menarche in Adolescent Girls: Analysis of the National Health and Nutrition Examination Survey 2003–2004"
},
{
"docid": "MED-4182",
"text": "Polybrominated diphenyl ether (PBDE) body burdens in the general U.S. population have been linked to the consumption of red meat and poultry. Exposure estimates have also indicated that meat products are a major contributor to PBDE dietary intake. To establish solid estimates of PBDE concentrations in domestic meat and poultry, samples from two statistically designed surveys of U.S. meat and poultry were analyzed for PBDEs. The two surveys were conducted in 2002-2003 and 2007-2008, between which times the manufacturing of penta-BDE and octa-BDE formulations had ceased in the United States (December 2004). Thus, the data provided an opportunity to observe prevalence and concentration trends that may have occurred during this time frame and to compare the mean PBDE levels among the meat and poultry industries. On the basis of composite samples, the average sum of the seven most prevalent PBDEs (BDE-28, -47, -99, -100, -153, -154, and -183) decreased by >60% from 1.95 ng/g lipid in 2002-2003 to 0.72 ng/g lipid in 2007-2008 for meat and poultry. PBDEs measured in individual samples in 2008 showed that beef samples had the lowest PBDE levels followed by hogs and chickens and then by turkeys. The PBDE congener pattern was the same for both surveys and resembled the penta-BDE formulation with BDE-47 and -99 accounting for 30 and 40% of the total, respectively. On the basis of the data from the two surveys, it appears that PBDE levels in U.S. meat and poultry have declined since manufacturing ceased; however, exposure pathways of PBDEs to livestock are still not known.",
"title": "Polybrominated diphenyl ethers in U.S. Meat and poultry from two statistically designed surveys showing trends and levels from 2002 to 2008."
},
{
"docid": "MED-2648",
"text": "The aim of this study was to compare results obtained by eight different short-term assays of estrogenlike actions of chemicals conducted in 10 different laboratories in five countries. Twenty chemicals were selected to represent direct-acting estrogens, compounds with estrogenic metabolites, estrogenic antagonists, and a known cytotoxic agent. Also included in the test panel were 17beta++-estradiol as a positive control and ethanol as solvent control. The test compounds were coded before distribution. Test methods included direct binding to the estrogen receptor (ER), proliferation of MCF-7 cells, transient reporter gene expression in MCF-7 cells, reporter gene expression in yeast strains stably transfected with the human ER and an estrogen-responsive reporter gene, and vitellogenin production in juvenile rainbow trout. 17beta-Estradiol, 17alpha-ethynyl estradiol, and diethylstilbestrol induced a strong estrogenic response in all test systems. Colchicine caused cytotoxicity only. Bisphenol A induced an estrogenic response in all assays. The results obtained for the remaining test compounds--tamoxifen, ICI 182.780, testosterone, bisphenol A dimethacrylate, 4-n-octylphenol, 4-n-nonylphenol, nonylphenol dodecylethoxylate, butylbenzylphthalate, dibutylphthalate, methoxychlor, o,p'-DDT, p,p'-DDE, endosulfan, chlomequat chloride, and ethanol--varied among the assays. The results demonstrate that careful standardization is necessary to obtain a reasonable degree of reproducibility. Also, similar methods vary in their sensitivity to estrogenic compounds. Thus, short-term tests are useful for screening purposes, but the methods must be further validated by additional interlaboratory and interassay comparisons to document the reliability of the methods.",
"title": "Comparison of Short-Term Estrogenicity Tests for Identification of Hormone-Disrupting Chemicals"
},
{
"docid": "MED-4183",
"text": "A previous study from our laboratory showed that pet cats had much higher serum levels of flame retardants compared to humans, despite sharing the same household environment. Dogs, on the other hand, are expected to have lower serum levels of flame retardants because they are metabolically better equipped to degrade these compounds. Thus, we hypothesized that dogs might be more similar to humans in their response to these environmental stressors and be better indicators of human exposures to these contaminants. Serum samples and their food were collected from 18 dogs and analyzed for PBDEs and other emerging flame retardants. The concentrations of PBDEs in dog serum and dog food averaged 1.8 ± 0.4 ng/g wet weight (ww) and 1.1 ± 0.2 ng/g ww, respectively. While the dog serum samples were dominated by the tetra to hepta BDE congeners, BDE-209 was the most abundant congener in the dog food. This difference in congener pattern was analyzed in terms of half-lives. Assuming food as the main exposure source, the average half-life in dog serum was 450 ± 170 days for the less brominated congeners and 2.3 ± 0.5 days for BDE-209. Dust was also considered as an additional exposure source, giving unreasonable residence times. In addition to PBDEs, other flame retardants, including Dechlorane Plus, decabromodiphenylethane, and hexabromocyclododecane, were identified in these samples.",
"title": "Flame retardants in the serum of pet dogs and in their food."
},
{
"docid": "MED-2653",
"text": "Human milk is the most important form of nourishment for newborn children. Its consumption is strongly recommended by health authorities also for other important advantages. Unfortunately, in the last three decades a great number of investigations have shown the occurrence of several environmental contaminants in human milk, especially those with lipophilic properties. This study investigates the presence of nonylphenol, octylphenol (OP), nonylphenol monoethoxylate (NP1EO) and two octylphenol ethoxylates (OPEOs) (namely OP1EO and OP2EO), in human breast milk of Italian women. NP was the contaminant found at the highest levels with mean concentrations of 32 ng/mL, about two orders of magnitude higher than OP (0.08 ng/mL), OP1EO (0.07 ng/mL) and OP2EO (0.16 ng/mL). In the group of study a positive correlation among fish consumption and levels of NP in the milk was observed, in accordance with the evidence that seafood represents one of the most important sources of exposure to this group of contaminants in Italy. On the basis of the concentrations found in the breast milk samples, a maximum NP daily intake of 3.94 microg/kg/day can be calculated, which is close to the Tolerable Daily Intake (TDI) of 5 microg/kg body weight (bw) proposed by the Danish Institute of Safety and Toxicology. In the cases of OP no TDI is available, but its intake is at least six orders of magnitude lower than the NOAEL of 10 mg/kg/day derived from a two generation study on rats.",
"title": "Nonylphenol and octylphenol in human breast milk."
},
{
"docid": "MED-3958",
"text": "Flanders is densely populated with much industry and intensive farming. Sexual maturation of adolescents (aged 14-15 years) was studied in relation to internal exposure to pollutants. Serum levels of pollutants and sex hormones were measured in 1679 participants selected as a random sample of the adolescents residing in the study areas. Data on sexual development were obtained from the medical school examination files. Self-assessment questionnaires provided information on health, use of medication and lifestyle factors. In boys, serum levels of hexachlorobenzene (HCB), p,p'-DDE and polychlorinated biphenyls (sum of marker PCB138, 153 and 180) were significantly and positively associated with pubertal staging (pubic hair and genital development). Higher levels of serum HCB and blood lead were associated with, respectively, a lower and a higher risk of gynecomastia. In girls, significant and negative associations were detected between blood lead and pubic hair development; higher exposure to PCBs was significantly associated with a delay in timing of menarche. Environmental exposures to pollutants at levels actually present in the Flemish population are associated with measurable effects on pubertal development. However, further understanding of toxic mode of action and sensitive windows of exposure is needed to explain the current findings.",
"title": "Internal exposure to pollutants and sexual maturation in Flemish adolescents."
},
{
"docid": "MED-3956",
"text": "Early onset of puberty may confer adverse health consequences. Thus, modifiable factors influencing the timing of puberty are of public health interest. Childhood overweight as a factor in the earlier onset of menarche has been supported by prospective evidence; nonetheless, its overall contribution may have been overemphasized, since secular trends toward a younger age at menarche have not been a universal finding during the recent obesity epidemic. Current observational studies suggest notable associations between dietary intakes and pubertal timing beyond contributions to an energy imbalance: children with the highest intakes of vegetable protein or animal protein experience pubertal onset up to 7 months later or 7 months earlier, respectively. Furthermore, girls with high isoflavone intakes may experience the onset of breast development and peak height velocity approximately 7-8 months later. These effect sizes are on the order of those observed for potentially neuroactive steroid hormones. Thus, dietary patterns characterized by higher intakes of vegetable protein and isoflavones and lower intakes of animal protein may contribute to a lower risk of breast cancer or a lower total mortality. © 2012 International Life Sciences Institute.",
"title": "Beyond overweight: nutrition as an important lifestyle factor influencing timing of puberty."
},
{
"docid": "MED-4178",
"text": "A method has been developed to identify pesticide residues and foodstuffs for inclusion in national monitoring programs with different priority levels. It combines two chronic dietary intake indicators: ATMDI based on maximum residue levels and agricultural uses, and EDI on food contamination data. The mean and 95th percentile of exposure were calculated for 490 substances using individual and national consumption data. The results show that mean ATMDI exceeds the acceptable daily intake (ADI) for 10% of the pesticides, and the mean upper-bound EDI is above the ADI for 1.8% of substances. A seven-level risk scale is presented for substances already analyzed in food in France and substances not currently sought. Of 336 substances analyzed, 70 pesticides of concern (levels 2-5) should be particularly monitored, 22 of which are priority pesticides (levels 4 and 5). Of 154 substances not sought, 36 pesticides of concern (levels 2-4) should be included in monitoring programs, including 8 priority pesticides (level 4). In order to refine exposure assessment, analytical improvements and developments are needed to lower the analytical limits for priority pesticide/commodity combinations. Developed nationally, this method could be applied at different geographic scales. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Chronic dietary risk characterization for pesticide residues: a ranking and scoring method integrating agricultural uses and food contamination data."
},
{
"docid": "MED-995",
"text": "This study was designed to determine the body burden of polybrominated diphenyl ethers (PBDEs) among first-time mothers in the Greater Boston, Massachusetts area and to explore key routes of exposure. We collected breast milk samples from 46 first-time mothers, 2-8 weeks after birth. We also sampled house dust from the homes of a subset of participants by vacuuming commonly used areas. Data on personal characteristics, diet, home furniture, and electrical devices were gathered from each participant using a questionnaire. Breast milk and dust samples were analyzed for PBDEs using gas chromatography/ mass spectrometry. PBDE concentrations were log-normally distributed in breast milk and dust. We found statistically significant, positive associations between PBDE concentrations in breast milk and house dust (r = 0.76, p = 0.003, not including BDE-209), as well as with reported dietary habits, particularly the consumption of dairy products (r = 0.41, p = 0.005) and meat (r = 0.37, p = 0.01). Due to low detection rates, it was not possible to draw conclusions about the association between BDE-209 in milk and dust. Our results support the hypothesis that the indoor environment and diet both play prominent roles in adult human exposure to PBDEs.",
"title": "Human exposure to PBDEs: associations of PBDE body burdens with food consumption and house dust concentrations."
},
{
"docid": "MED-2658",
"text": "The prevalence of allergic diseases has increased in recent decades. Allergic diseases, particularly asthma, are complex diseases with strong gene-environment interactions. Epidemiological studies have identified a variety of risk factors for the development of allergic diseases. Among them, endocrine-disrupting chemicals (EDCs) play an important role in triggering or exacerbating these diseases. 4-Nonylphenol (NP) and 4-octylphenol (OP)--two major alkylphenols--have been recognized as common toxic and xenobiotic endocrine disrupters. Due to their low solubility, high hydrophobicity, and low estrogenic activity, they tend to accumulate in the human body and may be associated with the adverse effects of allergic diseases. Recently, new evidence has supported the importance of alkylphenols in the in vitro allergic response. This review focuses on the effects of alkylphenols on several key cell types in the context of allergic inflammation. Copyright © 2012. Published by Elsevier B.V.",
"title": "Alkylphenols--potential modulators of the allergic response."
},
{
"docid": "MED-1004",
"text": "Background Exposure of the U.S. population to polybrominated diphenyl ethers (PBDEs) is thought to be via exposure to dust and diet. However, little work has been done to empirically link body burdens of these compounds to either route of exposure. Objectives The primary goal of this research was to evaluate the dietary contribution to PBDE body burdens in the United States by linking serum levels to food intake. Methods We used two dietary instruments—a 24-hr food recall (24FR) and a 1-year food frequency questionnaire (FFQ)—to examine food intake among participants of the 2003–2004 National Health and Nutrition Examination Survey. We regressed serum concentrations of five PBDEs (BDE congeners 28, 47, 99, 100, and 153) and their sum (∑PBDE) against diet variables while adjusting for age, sex, race/ethnicity, income, and body mass index. Results ∑PBDE serum concentrations among vegetarians were 23% (p = 0.006) and 27% (p = 0.009) lower than among omnivores for 24FR and 1-year FFQ, respectively. Serum levels of five PBDE congeners were associated with consumption of poultry fat: Low, medium, and high intake corresponded to geometric mean ∑PBDE concentrations of 40.6, 41.9, and 48.3 ng/g lipid, respectively (p = 0.0005). We observed similar trends for red meat fat, which were statistically significant for BDE-100 and BDE-153. No association was observed between serum PBDEs and consumption of dairy or fish. Results were similar for both dietary instruments but were more robust using 24FR. Conclusions Intake of contaminated poultry and red meat contributes significantly to PBDE body burdens in the United States.",
"title": "Diet Contributes Significantly to the Body Burden of PBDEs in the General U.S. Population"
},
{
"docid": "MED-4680",
"text": "OBJECTIVE: To investigate associations between dietary intakes throughout childhood and age at menarche, a possible indicator of future risk of disease, in a contemporary cohort of British girls. DESIGN: Diet was assessed by FFQ at 3 and 7 years of age, and by a 3 d unweighed food diary at 10 years. Age at menarche was categorised as before or after 12 years 8 months, a point close to the median age in this cohort. SETTING: Bristol, South-West England. SUBJECTS: Girls (n 3298) participating in the Avon Longitudinal Study of Parents and Children. RESULTS: Higher energy intakes at 10 years were positively associated with the early occurrence of menarche, but this association was removed on adjusting for body size. Total and animal protein intakes at 3 and 7 years were positively associated with age at menarche ≤12 years 8 months (adjusted OR for a 1 sd increase in protein at 7 years: 1·14 (95 % CI 1·04, 1·26)). Higher PUFA intakes at 3 and 7 years were also positively associated with early occurrence of menarche. Meat intake at 3 and 7 years was strongly positively associated with reaching menarche by 12 years 8 months (OR for menarche in the highest v. lowest category of meat consumption at 7 years: 1·75 (95 % CI 1·25, 2·44)). CONCLUSIONS: These data suggest that higher intakes of protein and meat in early to mid-childhood may lead to earlier menarche. This may have implications for the lifetime risk of breast cancer and osteoporosis.",
"title": "Diet throughout childhood and age at menarche in a contemporary cohort of British girls."
},
{
"docid": "MED-2645",
"text": "The development of the male reproductive ducts and external genitalia in vertebrates is dependent on elevated androgen concentrations during embryonic development and the period of postnatal growth. We have observed that a population of juvenile alligators living on Lake Apopka exhibit significantly smaller penis size (24% average decrease) and lower plasma concentrations of testosterone (70% lower concentrations) when compared to animals of similar size on Lake Woodruff. In addition to smaller phalli, no relationship exists between plasma testosterone concentrations and penile size in males from Lake Apopka, whereas a positive relationship exists for males from Lake Woodruff. The alligators on Lake Apopka are known to have elevated concentrations of the antiandrogenic DDT breakdown product p.p'-DDE stored in their fat. We suggest a number of hypotheses that could explain the modification in the phenotype of the juvenile male living in Lake Apopka. These modifications in phenotype include a smaller penis size, lower plasma androgen concentrations, and lack of responsiveness of the penis to the plasma androgens present.",
"title": "Reduction in penis size and plasma testosterone concentrations in juvenile alligators living in a contaminated environment."
},
{
"docid": "MED-3954",
"text": "BACKGROUND: A male epidemic of ischaemic heart disease (IHD) emerges with economic development. It has previously been hypothesised that this epidemic is due to nutritionally driven levels of pubertal sex steroids, which lead to a more atherogenic body shape and lipid profile in boys but not girls, without any sex-specific effects on glucose metabolism. This study tests this hypothesis by examining the association of childhood meat eating with IHD risk in a developing Chinese population. METHODS: Multivariable linear and censored regression was used in a cross-sectional study of 19,418 Chinese older (≥ 50 years) men and women from the Guangzhou Biobank Cohort Study (phases 2 and 3) to assess the adjusted associations of childhood meat eating with waist to hip ratio (WHR), high-density lipoprotein cholesterol and fasting plasma glucose. RESULTS: Adjusted for age, childhood hunger, life-course socioeconomic position and current lifestyle childhood almost daily meat eating compared with less than weekly meat eating was associated with higher WHR (0.007, 95% CI 0.0003 to 0.01) in men but not women. No association with fasting glucose was observed. CONCLUSIONS: Given the potential limitations of this study, especially the crude nature of the exposure and modest findings, the results should be considered as preliminary. However, they do lend support to the hypothesis that the male epidemic of premature IHD and sexual divergence in IHD rates that occur with economic development may be nutritionally driven in childhood. In elucidating the developmental origins of non-communicable chronic diseases, more attention should be focused on the sociohistorical context and the role of puberty.",
"title": "Does childhood meat eating contribute to sex differences in risk factors for ischaemic heart disease in a developing population?"
},
{
"docid": "MED-4174",
"text": "Perfluorooctanesulfonyl fluoride based compounds have been used in a wide variety of consumer products, such as carpets, upholstery, and textiles. These compounds degrade to perfluorooctanesulfonate (PFOS), a persistent metabolite that accumulates in tissues of humans and wildlife. Previous studies have reported the occurrence of PFOS, perfluorohexanesulfonate (PFHxS), perfluorooctanoate (PFOA), and perfluorooctanesulfonamide (PFOSA) in human sera collected from the United States. In this study, concentrations of PFOS, PFHxS, PFOA, and PFOSA were measured in 473 human blood/serum/plasma samples collected from the United States, Colombia, Brazil, Belgium, Italy, Poland, India, Malaysia, and Korea. Among the four perfluorochemicals measured, PFOS was the predominant compound found in blood. Concentrations of PFOS were the highest in the samples collected from the United States and Poland (>30 ng/mL); moderate in Korea, Belgium, Malaysia, Brazil, Italy, and Colombia (3 to 29 ng/mL); and lowest in India (<3 ng/mL). PFOA was the next most abundant perfluorochemical in blood samples, although the frequency of occurrence of this compound was relatively low. No age- or gender-related differences in the concentrations of PFOS and PFOA were found in serum samples. The degree of association between the concentrations of four perfluorochemicals varied, depending on the origin of the samples. These results suggested the existence of sources with varying levels and compositions of perfluorochemicals, and differences in exposure patterns to these chemicals, in various countries. In addition to the four target fluorochemicals measured, qualitative analysis of selected blood samples showed the presence of other perfluorochemicals such as perfluorodecanesulfonate (PFDS), perfluoroheptanoic acid (PFHpA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluorododecanoic acid (PFDoA), and perfluoroundecanoic acid (PFUnDA) in serum samples, at concentrations approximately 5- to 10-fold lower than the concentration of PFOS. Further studies should focus on identifying sources and pathways of human exposure to perfluorochemicals.",
"title": "Perfluorooctanesulfonate and related fluorochemicals in human blood from several countries."
},
{
"docid": "MED-2662",
"text": "A human breast cancer cell line (MCF-7) was used to develop an in vitro screening assay for the detection of xenoestrogenic environmental pollutants. MCF-7 cells were cultured in DMEM containing 5% fetal bovine serum (FBS). An estrogenic response was defined as an increase in the frequency of proliferating MCF-7 cells, and was measured using a thymidine analog, bromodeoxyuridine, and flow cytometry. Di-2-ethylhexyl phthalate (DEHP) and 4-n-nonylphenol (4-n-NP) were used as model chemicals. The proliferation rate of S-phase cells after 24 h of exposure to various concentrations of 17beta-estradiol and to model compounds was compared with a positive and a negative control, containing 1 nM 17beta-estradiol and 0.1% ethanol, respectively. DEHP and 4-n-NP increased the frequency of proliferating MCF-7 cells in a dose-dependent manner. The lowest concentration that significantly increased the proliferation of MCF-7 cells was 10 microM for DEHP and 1 microM for 4-n-NP. The results showed that the assay is accurate and quick to perform. It may prove a valuable tool for screening potential estrogen-mimicking environmental pollutants.",
"title": "Effects of xenoestrogenic environmental pollutants on the proliferation of a human breast cancer cell line (MCF-7)."
},
{
"docid": "MED-4551",
"text": "Interest has increased in the possibility that maternal dietary intake during pregnancy might influence the development of allergic disorders in children. The present prospective study examined the association of maternal intake of selected foods high in fatty acids and specific types of fatty acids during pregnancy with the risk of suspected atopic eczema among Japanese infants aged 3-4 months. Subjects were 771 mother-child pairs. Information on maternal dietary intake during pregnancy was assessed with a validated self-administered diet history questionnaire. The term 'suspected atopic eczema' was used to define an outcome based on results of our questionnaire completed by mothers 3-4 months postpartum. The risk of suspected atopic eczema was 8.4% (n = 65). Higher maternal intake of meat during pregnancy was significantly associated with an increased risk of suspected atopic eczema in the offspring: the multivariate odds ratio (OR) for the highest vs. lowest quartile was 2.59 [95% confidence interval (CI): 1.15-6.17, p for trend = 0.01]. The positive association was strengthened when the definition of the outcome was confined to a definite physician's diagnosis of atopic eczema (n = 35): the multivariate OR between extreme quartiles was 3.53 (95% CI: 1.19-12.23, p for trend = 0.02). No material exposure-response relationships were observed between maternal intake of eggs, dairy products, fish, total fat, saturated fatty acids, monounsaturated fatty acids, n-3 polyunsaturated fatty acids, alpha-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, n-6 polyunsaturated fatty acids, linoleic acid, arachidonic acid and cholesterol and the ratio of n-3 to n-6 polyunsaturated fatty acid consumption and the risk of suspected atopic eczema. Higher maternal meat intake may increase the risk of infantile atopic eczema, whereas we found no evidence that maternal intake of fish and n-3 polyunsaturated fatty acids are preventive against infantile atopic eczema. (c) 2009 John Wiley & Sons A/S",
"title": "Maternal meat and fat consumption during pregnancy and suspected atopic eczema in Japanese infants aged 3-4 months: the Osaka Maternal and Child He..."
}
] |
[
{
"docid": "MED-5104",
"text": "We and others recently began studying brominated flame retardant levels in various matrices in the US including human milk and other food. This paper reviews the food studies. In our studies, ten to thirteen polybrominated diphenyl ether (PBDE) congeners were measured, usually including BDE 209. All US women's milk samples were contaminated with PBDEs from 6 to 419 ng/g, lipid, orders of magnitude higher than levels reported in European studies, and are the highest reported worldwide. We compared our market basket studies of meat, fish and dairy products with other US food studies of meat and fish. US studies showed somewhat higher levels of PBDEs than reported elsewhere. Fish were most highly contaminated (median 616 pg/g), then meat (median190 pg/g) and dairy products (median 32.2 pg/g). However, unlike some European countries where fish predominates, dietary intake of PBDEs in the US is mostly from meat, then fish and then dairy products. Broiling can decrease the amount of PBDEs per serving. We also measured levels of hexabromocyclododecane (HBCD), another brominated flame retardant, in human milk. The levels are lower than PBDEs, 0.16-1.2 ng/g, similar to European levels, unlike PBDEs where US levels are much higher than European levels.",
"title": "Brominated flame retardants in US food."
},
{
"docid": "MED-2391",
"text": "Objectives The objective of this article is to extend our previous studies of persistent organic pollutant (POP) contamination of U.S. food by measuring perfluorinated compounds (PFCs), organochlorine pesticides, and polychlorinated biphenyls (PCBs) in composite food samples. This study is part of a larger study reported in two articles, the other of which reports levels of polybrominated diphenyl ethers and hexabromocyclododecane brominated flame retardants in these composite foods [Schecter et al. 2010. Polybrominated diphenyl ethers (PBDEs) and hexabromocyclodecane (HBCD) in composite U.S. food samples, Environ Health Perspect 118:357–362]. Methods In this study we measured concentrations of 32 organochlorine pesticides, 7 PCBs, and 11 PFCs in composite samples of 31 different types of food (310 individual food samples) purchased from supermarkets in Dallas, Texas (USA), in 2009. Dietary intake of these chemicals was calculated for an average American. Results Contamination varied greatly among chemical and food types. The highest level of pesticide contamination was from the dichlorodiphenyltrichloroethane (DDT) metabolite p,p′- dichlorodiphenyldichloroethylene, which ranged from 0.028 ng/g wet weight (ww) in whole milk yogurt to 2.3 ng/g ww in catfish fillets. We found PCB congeners (28, 52, 101, 118, 138, 153, and 180) primarily in fish, with highest levels in salmon (PCB-153, 1.2 ng/g ww; PCB-138, 0.93 ng/g ww). For PFCs, we detected perfluorooctanoic acid (PFOA) in 17 of 31 samples, ranging from 0.07 ng/g in potatoes to 1.80 ng/g in olive oil. In terms of dietary intake, DDT and DDT metabolites, endosulfans, aldrin, PCBs, and PFOA were consumed at the highest levels. Conclusion Despite product bans, we found POPs in U.S. food, and mixtures of these chemicals are consumed by the American public at varying levels. This suggests the need to expand testing of food for chemical contaminants.",
"title": "Perfluorinated Compounds, Polychlorinated Biphenyls, and Organochlorine Pesticide Contamination in Composite Food Samples from Dallas, Texas, USA"
},
{
"docid": "MED-2484",
"text": "Paediatric asthma is a major clinical concern worldwide and represents a huge burden on family and society. It accounts for a large number of lost school days and may deprive the child of both academic achievement and social interaction. Childhood asthma also places strain on healthcare resources as a result of doctor and hospital visits and the cost of treatment. The prevalence of asthma varies worldwide, possibly because of different exposure to respiratory infection, indoor and outdoor pollution, and diet. Certain risk factors appear to predispose children to developing asthma and atopic disease, including incidence and severity of wheezing, atopy, maternal smoking, and number of fever episodes. This paper discusses the burden, prevalence, and risk factors associated with paediatric asthma.",
"title": "The burden of childhood asthma"
},
{
"docid": "MED-5238",
"text": "The prevalence of diabetes and obesity has increased rapidly over the last few decades in both developed and developing countries. While it is intuitively appealing to suggest that lifestyle risk factors such as decreased physical activity and adoption of poor diets can explain much of the increase, the evidence to support this is poor. Given this, there has been an impetus to look more widely than traditional lifestyle and biomedical risk factors, especially those risk factors, which arise from the environment. Since the industrial revolution, there has been an introduction of many chemicals into our environment, which have now become environmental pollutants. There has been growing interest in one key class of environmental pollutants known as persistent organic pollutants (POPs) and their potential role in the development of diabetes. This review will summarise and appraise the current epidemiological evidence relating POPs to diabetes and highlight gaps and flaws in this evidence. Copyright © 2013 Elsevier Masson SAS. All rights reserved.",
"title": "Persistent organic pollutants and diabetes: a review of the epidemiological evidence."
},
{
"docid": "MED-2905",
"text": "Fish consumption during gestation can provide the fetus with long chain polyunsaturated fatty acids (LCPUFA) and other nutrients essential for growth and development of the brain. However, fish consumption also exposes the fetus to the neurotoxicant, methyl mercury (MeHg). We studied the association between these fetal exposures and early child development in the Seychelles Child Development Nutrition Study (SCDNS). Specifically, we examined a priori models of Ω-3 and Ω-6 LCPUFA measures in maternal serum to test the hypothesis that these LCPUFA families before or after adjusting for prenatal MeHg exposure would reveal associations with child development assessed by the BSID-II at ages 9 and 30 months. There were 229 children with complete outcome and covariate data available for analysis. At 9 months, the PDI was positively associated with total Ω-3 LCPUFA and negatively associated with the ratio of Ω-6/Ω-3 LCPUFA. These associations were stronger in models adjusted for prenatal MeHg exposure. Secondary models suggested that the MeHg effect at 9 months varied by the ratio of Ω-6/Ω-3 LCPUFA. There were no significant associations between LCPUFA measures and the PDI at 30 months. There were significant adverse associations, however, between prenatal MeHg and the 30 month PDI when the LCPUFA measures were included in the regression analysis. The BSID-II Mental Developmental Index (MDI) was not associated with any exposure variable. These data support the potential importance to child development of prenatal availability of Ω-3 LCPUFA present in fish and of LCPUFA in the overall diet. Furthermore, they indicate that the beneficial effects of LCPUFA can obscure the determination of adverse effects of prenatal MeHg exposure in longitudinal observational studies.",
"title": "Associations of maternal long chain polyunsaturated fatty acids, methyl mercury, and infant development in the Seychelles Child Development Nutrition Study"
},
{
"docid": "MED-3032",
"text": "Fish consumption during gestation can provide the fetus with long chain polyunsaturated fatty acids (LCPUFA) and other nutrients essential for growth and development of the brain. However, fish consumption also exposes the fetus to the neurotoxicant, methyl mercury (MeHg). We studied the association between these fetal exposures and early child development in the Seychelles Child Development Nutrition Study (SCDNS). Specifically, we examined a priori models of Ω-3 and Ω-6 LCPUFA measures in maternal serum to test the hypothesis that these LCPUFA families before or after adjusting for prenatal MeHg exposure would reveal associations with child development assessed by the BSID-II at ages 9 and 30 months. There were 229 children with complete outcome and covariate data available for analysis. At 9 months, the PDI was positively associated with total Ω-3 LCPUFA and negatively associated with the ratio of Ω-6/Ω-3 LCPUFA. These associations were stronger in models adjusted for prenatal MeHg exposure. Secondary models suggested that the MeHg effect at 9 months varied by the ratio of Ω-6/Ω-3 LCPUFA. There were no significant associations between LCPUFA measures and the PDI at 30 months. There were significant adverse associations, however, between prenatal MeHg and the 30 month PDI when the LCPUFA measures were included in the regression analysis. The BSID-II Mental Developmental Index (MDI) was not associated with any exposure variable. These data support the potential importance to child development of prenatal availability of Ω-3 LCPUFA present in fish and of LCPUFA in the overall diet. Furthermore, they indicate that the beneficial effects of LCPUFA can obscure the determination of adverse effects of prenatal MeHg exposure in longitudinal observational studies.",
"title": "Associations of maternal long chain polyunsaturated fatty acids, methyl mercury, and infant development in the Seychelles Child Development Nutrition Study"
},
{
"docid": "MED-5099",
"text": "There is controversy about the risks and benefits of consuming fish. Fish consumption provides nutrients, some of which are essential for brain growth and development. All fish, however, contain methyl mercury (MeHg), a known neurotoxicant. The toxic effect of MeHg seems most damaging during brain development, and thus, prenatal exposure is of greatest concern. At present the level of prenatal exposure associated with risk to a child's neurodevelopment is not known. Balancing the rewards and possible risks of fish consumption presents a dilemma to consumers and regulatory authorities. We review the nutrients in fish that are important in brain development and the current evidence of risk from MeHg at exposure levels achieved by consuming fish. We then review the findings from a large prospective cohort study of a population that consumes fish daily, the Seychelles Child Development Study. The MeHg content of the fish consumed in the Seychelles is similar to that of ocean fish available in industrialized countries, so they represent a sentinel population for any risk from fish consumption. In the Seychelles, evaluations of the children through 9 y of age show no consistent pattern of adverse associations with prenatal MeHg exposure. Recent studies in the Seychelles have focused on nutrients in fish that might influence a child's development, including long-chain polyunsaturated fatty acids, iodine, iron, and choline. Preliminary findings from this study suggest that the beneficial influence of nutrients from fish may counter any adverse effects of MeHg on the developing nervous system.",
"title": "Nutrient and methyl mercury exposure from consuming fish."
},
{
"docid": "MED-2497",
"text": "The birth cohort BraMat (n = 205; a sub-cohort of the Norwegian Mother and Child Cohort Study (MoBa) conducted by the Norwegian Institute of Public Health) was established to study whether prenatal exposure to toxicants from the maternal diet affects immunological health outcomes in children. We here report on the environmental pollutants polychlorinated biphenyls (PCBs) and dioxins, as well as acrylamide generated in food during heat treatment. The frequency of common infections, eczema or itchiness, and periods of more than 10 days of dry cough, chest tightness or wheeze (called wheeze) in the children during the first year of life was assessed by questionnaire data (n = 195). Prenatal dietary exposure to the toxicants was estimated using a validated food frequency questionnaire from MoBa. Prenatal exposure to PCBs and dioxins was found to be associated with increased risk of wheeze and exanthema subitum, and also with increased frequency of upper respiratory tract infections. We found no associations between prenatal exposure to acrylamide and the health outcomes investigated. Our results suggest that prenatal dietary exposure to dioxins and PCBs may increase the risk of wheeze and infectious diseases during the first year of life. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Prenatal exposure to polychlorinated biphenyls and dioxins is associated with increased risk of wheeze and infections in infants."
},
{
"docid": "MED-2396",
"text": "Rates of type 2 diabetes mellitus (T2DM), both in the United States and worldwide, have been rising at an alarming rate over the last two decades. Because this disease is viewed as primarily being attributable to unhealthy lifestyle habits, a great deal of emphasis has been placed on encouraging increased exercise, better dietary habits, and weight loss. Recent studies reveal that the presence of several persistent organic pollutants (POPs) can confer greater risk for developing the disease than some of the established lifestyle risk factors. In fact, evidence suggests the hypothesis that obesity might only be a significant risk factor when adipose tissue contains high amounts of POPs. Chlorinated pesticides and polychlorinated biphenyls, in particular, have been strongly linked to the development of metabolic syndrome, insulin resistance, and T2DM. In addition to reviewing the evidence associating POPs to these conditions, this article explores the possible contribution of farmed Atlantic salmon - a significant and common dietary source of POPs - with blood sugar dysregulation conditions.",
"title": "The role of persistent organic pollutants in the worldwide epidemic of type 2 diabetes mellitus and the possible connection to Farmed Atlantic Salm..."
},
{
"docid": "MED-4739",
"text": "Contemporary reproductive aged women and their offspring are facing an unprecedented onslaught of toxicant exposures from myriad sources in their day-to-day life. Public health recommendations regarding optimal diet and nutrition in pregnancy must incorporate several considerations including safety of available foodstuffs, cultural practices and lifestyle issues. Gestational consumption of contaminated seafood remains a potential source of toxicant exposure, including mercury, for the developing child. Health care professionals responsible for the care of women and their developing children need to become apprised of: a) risks associated with toxicant bioaccumulation in pregnancy; b) ongoing information emerging in the important field of reproductive toxicology; and c) strategies within the clinical setting to facilitate nutritional sufficiency and precautionary avoidance of adverse exposure among young women.",
"title": "Nowhere to hide: Chemical toxicants and the unborn child."
},
{
"docid": "MED-5097",
"text": "Purpose of review To summarize recent evidence regarding associations of early life exposure to mercury from maternal fish consumption during pregnancy, thimerosal in vaccines and dental amalgam with child neurodevelopment. Recent findings Recent publications have built upon previous evidence demonstrating mild detrimental neurocognitive effects from prenatal methylmercury exposure from maternal fish consumption during pregnancy. New studies examining the effects of prenatal fish consumption as well as methylmercury suggest there are benefits from prenatal fish consumption, but also that consumption of fish high in mercury should be avoided. Future studies incorporating information on both the methylmercury and the docosahexaenoic acid contained within fish will help to refine recommendations to optimize outcomes for mothers and children. Additional recent studies have supported the safety of vaccines containing thimerosal and of dental amalgam for repair of dental caries in children. Summary Exposure to mercury may harm child development. Interventions intended to reduce exposure to low levels of mercury in early life must, however, be carefully evaluated in consideration of the potential attendant harm from resultant behavior changes, such as reduced docosahexaenoic acid exposure from lower seafood intake, reduced uptake of childhood vaccinations and suboptimal dental care.",
"title": "Fish consumption, methylmercury and child neurodevelopment"
},
{
"docid": "MED-853",
"text": "OBJECTIVE: To present a child who developed gastric ulcers and duodenal erosions after ingestion of hydrogen peroxide 3% and delineate the epidemiology, medical outcomes, and toxicity of exposures to this agent managed by a poison control center. METHODS: A retrospective chart review of exposures to hydrogen peroxide 3% reported to the Long Island Regional Poison Control Center from January 1992 to April 1995 was conducted. Data extracted included age, route of exposure, amount of agent, symptoms, therapy, and medical outcome. RESULTS: There were 670 exposures to hydrogen peroxide 3% of 81,126 total exposures reported during the 40 months. Most exposures were by oral route (77%), occurred in children < 17 years old (67%), and were asymptomatic (85.6%). All but one exposure resulted in a benign outcome. One child, who presented with bloody emesis, developed multiple gastric ulcers and duodenal erosions after ingestion of hydrogen peroxide 2-4 oz. CONCLUSIONS: Exposure to hydrogen peroxide 3% is usually benign, however, severe gastric injury may occur following small ingestions in children. Patients who report persistent vomiting or bloody emesis require medical evaluation and consideration of endoscopy to evaluate gastrointestinal injury.",
"title": "Hydrogen peroxide 3% exposures."
},
{
"docid": "MED-2407",
"text": "Background Persistent organic pollutants (POPs) are hazardous chemicals omnipresent in our food chain, which have been internationally regulated to ensure public health. Initially described for their potency to affect reproduction and promote cancer, recent studies have highlighted an unexpected implication of POPs in the development of metabolic diseases like type 2 diabetes and obesity. Based on this novel knowledge, this article aims at stimulating discussion and evaluating the effectiveness of current POP legislation to protect humans against the risk of metabolic diseases. Furthermore, the regulation of POPs in animal food products in the European Union (EU) is addressed, with a special focus on marine food since it may represent a major source of POP exposure to humans. Discussion There is mounting scientific evidence showing that current POP risk assessment and regulation cannot effectively protect humans against metabolic disorders. Better regulatory control of POPs in dietary products should be of high public health priority. Summary The general population is exposed to sufficient POPs, both in term of concentration and diversity, to induce metabolic disorders. This situation should attract the greatest attention from the public health and governmental authorities.",
"title": "Public health concern behind the exposure to persistent organic pollutants and the risk of metabolic diseases"
},
{
"docid": "MED-4949",
"text": "Methyl mercury is a developmental neurotoxicant. Exposure results principally from consumption by pregnant women of seafood contaminated by mercury from anthropogenic (70%) and natural (30%) sources. Throughout the 1990s, the U.S. Environmental Protection Agency (EPA) made steady progress in reducing mercury emissions from anthropogenic sources, especially from power plants, which account for 41% of anthropogenic emissions. However, the U.S. EPA recently proposed to slow this progress, citing high costs of pollution abatement. To put into perspective the costs of controlling emissions from American power plants, we have estimated the economic costs of methyl mercury toxicity attributable to mercury from these plants. We used an environmentally attributable fraction model and limited our analysis to the neurodevelopmental impacts—specifically loss of intelligence. Using national blood mercury prevalence data from the Centers for Disease Control and Prevention, we found that between 316,588 and 637,233 children each year have cord blood mercury levels > 5.8 μg/L, a level associated with loss of IQ. The resulting loss of intelligence causes diminished economic productivity that persists over the entire lifetime of these children. This lost productivity is the major cost of methyl mercury toxicity, and it amounts to $8.7 billion annually (range, $2.2–43.8 billion; all costs are in 2000 US$). Of this total, $1.3 billion (range, $0.1–6.5 billion) each year is attributable to mercury emissions from American power plants. This significant toll threatens the economic health and security of the United States and should be considered in the debate on mercury pollution controls.",
"title": "Public Health and Economic Consequences of Methyl Mercury Toxicity to the Developing Brain"
},
{
"docid": "MED-2471",
"text": "The International Study of Asthma and Allergies in Childhood (ISAAC) Phase One showed large worldwide variations in the prevalence of symptoms of asthma, rhinoconjunctivitis and eczema, up to 10 to 20 fold between countries. Ecological analyses were undertaken with ISAAC Phase One data to explore factors that may have contributed to these variations, and are summarised and reviewed here. In ISAAC Phase One the prevalence of symptoms in the past 12 months of asthma, rhinoconjunctivitis and eczema were estimated from studies in 463,801 children aged 13 - 14 years in 155 centres in 56 countries, and in 257,800 children aged 6-7 years in 91 centres in 38 countries. Ecological analyses were undertaken between symptom prevalence and the following: Gross National Product per capita (GNP), food intake, immunisation rates, tuberculosis notifications, climatic factors, tobacco consumption, pollen, antibiotic sales, paracetamol sales, and outdoor air pollution. Symptom prevalence of all three conditions was positively associated with GNP, trans fatty acids, paracetamol, and women smoking, and inversely associated with food of plant origin, pollen, immunisations, tuberculosis notifications, air pollution, and men smoking. The magnitude of these associations was small, but consistent in direction between conditions. There were mixed associations of climate and antibiotic sales with symptom prevalence. The potential causality of these associations warrant further investigation. Factors which prevent the development of these conditions, or where there is an absence of a positive correlation at a population level may be as important from the policy viewpoint as a focus on the positive risk factors. Interventions based on small associations may have the potential for a large public health benefit.",
"title": "Which population level environmental factors are associated with asthma, rhinoconjunctivitis and eczema? Review of the ecological analyses of ISAAC Phase One"
},
{
"docid": "MED-2067",
"text": "A number of natural compounds with inhibitory effects on tumorigenesis have been identified from our diet. Several studies have documented the cancer-preventive activity of a significant number of isothiocyanates (ITCs), the majority of which occur in plants, especially in Cruciferous vegetables. The most characterized ITC is sulforaphane (SFN). SFN has received a great deal of attention because of its ability to simultaneously modulate multiple cellular targets involved in cancer development, including: (i) DNA protection by modulating carcinogen-metabolizing enzymes and blocking the action of mutagens; (ii) inhibition of cell proliferation and induction of apoptosis, thereby retarding or eliminating clonal expansion of initiated, transformed, and/or neoplastic cells; (iii) inhibition of neoangiogenesis, progression of benign tumors to malignant tumors, and metastasis formation. SFN is therefore able to prevent, delay, or reverse preneoplastic lesions, as well as to act on cancer cells as a therapeutic agent. Taking into account this evidence and its favorable toxicological profile, SFN can be viewed as a conceptually promising agent in cancer prevention and/or therapy.",
"title": "Sulforaphane as a promising molecule for fighting cancer."
},
{
"docid": "MED-4744",
"text": "OBJECTIVES: To quantify maternal perceptions regarding the quality of their child's diet, and to identify factors associated with misperceptions. STUDY DESIGN: A representative sample of 2287 children aged 2-5 years from a cross-sectional study (GENESIS study) was used. METHODS: Maternal perceptions of the quality of their child's diet, child's and mother's anthropometric characteristics, and other characteristics (i.e. socio-demographic and lifestyle) were recorded. The actual quality of each child's diet was estimated using the Healthy Eating Index (HEI) score. RESULTS: Based on the HEI score, 18.3% of participants had a 'poor' diet, 81.5% had a diet which 'needs improvement' and only 0.2% had a 'good' diet. Almost 83% of mothers overestimated the quality of their child's diet. The overestimation rate was 86% among mothers who declared that they choose their child's food based on what they consider to be healthy, and 72% among those who reported that other factors play the predominant role in food choices for their child (P<0.001). Moreover, total energy intake as well as the intake of fruits, grains, vegetables, meat and milk was significantly higher among children whose mothers overestimated the quality of their diet. CONCLUSION: The vast majority of mothers overestimate the quality of their child's diet. Given that maternal perceptions regarding the quality of their child's diet are likely to be one of the predominant factors determining the child's food intake, health professionals should make mothers aware of the existence of particular dietary recommendations that their children should meet in order to eat a healthy diet.",
"title": "Diet quality of preschool children and maternal perceptions/misperceptions: the GENESIS study."
},
{
"docid": "MED-3601",
"text": "Experimentation involving children is not a new phenomenon. Children have been used as research subjects in a diverse set of experiments, including the trials of new vaccines and sera, in efforts to understand normal pediatric anatomy and physiology and in the development of new drugs and procedures. Concern about child participants in research is also not a new development. For more than a century, critics of medical research have called attention to the fact that children and other vulnerable populations--pregnant women, prisoners, the mentally ill--have too often served as the unwitting and unwilling subjects of medical experiments. This paper looks at several early cases in which children participated, including the first trial of cowpox vaccine, the first human trial of rabies vaccine, and the first treatment of Listerian wound antisepsis. The history of concern for children, especially institutionalized children, in medical research is considered along with the development of regulations or guidelines, including the Declaration of Helsinki (1964).",
"title": "Children as guinea pigs: historical perspective."
},
{
"docid": "MED-5209",
"text": "A 5-year-old boy with autism developed dry eye and xerophthalmia. Serum vitamin A was undetectable. Dietary history revealed a markedly altered intake consisting of only fried potatoes and rice balls for 2 years. Fried potatoes contain no vitamin A. Autism is a multifaceted developmental disorder infrequently accompanied by abnormal eating practices. To the authors' knowledge, most children with autism who develop dietary vitamin A deficiency have consumed an excess of fried potatoes. Attention to possible vitamin A deficiency is essential when fried potatoes are consumed exclusively.",
"title": "Fried-potato diet causes vitamin A deficiency in an autistic child."
},
{
"docid": "MED-2476",
"text": "An increase in asthma and atopic disease has been recorded in many countries where society has become more prosperous. We have investigated two possible explanations: a reduction in childhood infections and a change in diet. In a cohort of people followed up since 1964, originally selected as a random sample of primary school children, we have investigated the relevance of family size and the common childhood infectious diseases to development of eczema, hay fever and asthma. Although membership of a large family reduced risks of hay fever and eczema (but not asthma), this was not explained by the infections the child had suffered. Indeed, the more infections the child had had, the greater the likelihood of asthma, although measles gave a modest measure of protection. We have investigated dietary factors in two separate studies. In the first, we have shown the risks of bronchial hyper-reactivity are increased seven-fold among those with the lowest intake of vitamin C, while the lowest intake of saturated fats gave a 10-fold protection. In the second, we have shown that the risk of adult-onset wheezy illness is increased five-fold by the lowest intake of vitamin E and doubled by the lowest intake of vitamin C. These results were supported by direct measurements of the vitamins and triglycerides in plasma. We have proposed that changes in the diet of pregnant women may have reflected those observed in the population as a whole and that these may have resulted in the birth of cohorts of children predisposed to atopy and asthma. The direct test of this is to study the diet and nutritional status of a large cohort of pregnant women and to follow their offspring forward. This is our current research.",
"title": "Diet, infection and wheezy illness: lessons from adults."
},
{
"docid": "MED-3372",
"text": "The purpose of this study was to investigate the role of parent and child characteristics in explaining children's fruit and vegetable intakes. In 2008, parents of preschoolers (mean age 3.5 years) from 56 schools in Belgium-Flanders completed questionnaires including a parent and child fruit and vegetable food frequency questionnaire, general parenting styles (laxness, overreactivity and positive interactions), specific food parenting practices (child-centered and parent-centered feeding practices) and children's characteristics (children's shyness, emotionality, stubbornness, activity, sociability, and negative reactions to food). Multiple linear regression analyses (n = 755) indicated a significant positive association between children's fruit and vegetable intake and parent's intake and a negative association with children's negative reactions to food. No general parenting style dimension or child personality characteristic explained differences in children's fruit and vegetable intakes. Child-centered feeding practices were positively related to children's fruit and vegetable intakes, while parent-centered feeding practices were negatively related to children's vegetable intakes. In order to try to increase children's fruit and vegetable consumption, parents should be guided to improve their own diet and to use child-centered parenting practices and strategies known to decrease negative reactions to food. Copyright © 2010 Elsevier Ltd. All rights reserved.",
"title": "Associations of parenting styles, parental feeding practices and child characteristics with young children's fruit and vegetable consumption."
},
{
"docid": "MED-4937",
"text": "In the late 1960s the first scientific studies on contamination in Antarctica demonstrated the presence of pollutants in Antarctic ecosystems. Many Persistent Organic Pollutants (POPs) are transported globally from the areas in which they are produced and released into the environment in remote areas, including Antarctica. Here we report results obtained concerning the accumulation of polybrominated diphenyl ethers (PBDEs), mono- and non-ortho-polychlorobiphenyls (PCBs), polychlorodibenzodioxins (PCDDs) and polychlorodibenzofurans (PCDFs) in the tissues of two species of Antarctic fish (Chionodraco hamatus and Trematomus bernacchii). The 2,3,7,8-TCDD toxic equivalents (TEQs) were also calculated to evaluate the potential risk of these compounds for the two species. In general, POP levels were higher in the tissues of T. bernacchii than in C. hamatus and the highest concentrations were found in the liver of both species. The PBDE levels varied from 160.5 pg g(-1) wet wt in C. hamatus muscle to 789.9 pg g(-1) wet wt in T. bernacchii liver and were lower than the levels of PCBs. PCBs were the main organochlorine compounds detected and their concentrations ranged from 0.3 ng g(-1) wet wt in C. hamatus muscle to 15.1 ng g(-1) wet wt in T. bernacchii liver. TEQ concentrations resulted higher in C. hamatus than in T. bernacchii and were due mainly to PCDDs. The presence of PBDEs and organochlorine pollutants in the tissues of Antarctic organisms confirms their global transport and distribution.",
"title": "Levels of polybrominated diphenyl ethers (PBDEs) and organochlorine pollutants in two species of Antarctic fish (Chionodraco hamatus and Trematomus..."
},
{
"docid": "MED-3012",
"text": "The fish ingredient N3-docosahexaenoic acid 22:6 n-3 (DHA) stimulates brain development. On the other hand methylmercury (MeHg) in fish disturbs the developing central nervous system. In this Context the IQ score in children is considered as an aggregate measure of in utero brain development. To determine the effect of DHA exposure on prenatal neurodevelopment the maternal DHA intake during pregnancy was compared with its epidemiologically observed effect on the IQ score of children. For MeHg the maternal intake was converted into its accumulation in the maternal body. The maternal body burden then was compared with its epidemiologically observed relationship with the IQ score. Taking the MeHg and DHA content of 33 fish species the net effect of these compounds on the IQ score was quantified. For most fish species the adverse effect of MeHg on the IQ score exceeded the beneficial effect of DHA. In the case of long-living predators a negative effect up to 10 points on the IQ score was found. The results of this study indicate that food interventions aiming at the beneficial effects of fish consumption should focus on fish species with a high DHA content, while avoiding fish species with a high MeHg content. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Fish consumption during child bearing age: a quantitative risk-benefit analysis on neurodevelopment."
},
{
"docid": "MED-1099",
"text": "Pollutant chemicals that are widespread in the environment can affect endocrine signaling, as evidenced in laboratory experiments and in wildlife with relatively high exposures. Although humans are commonly exposed to such pollutant chemicals, the exposures are generally low, and clear effects on endocrine function from such exposures have been difficult to demonstrate. Several instances in which there are data from humans on exposure to the chemical agent and the endocrine outcome are reviewed, including age at weaning, age at puberty, and sex ratio at birth, and the strength of the evidence is discussed. Although endocrine disruption in humans by pollutant chemicals remains largely undemonstrated, the underlying science is sound and the potential for such effects is real.",
"title": "Evidence of effects of environmental chemicals on the endocrine system in children."
},
{
"docid": "MED-4932",
"text": "Annual global aquaculture production has more than tripled within the past 15 years, and by 2015, aquaculture is predicted to account for 39% of total global seafood production by weight. Given that lack of adequate nutrition is a leading contributor to the global burden of disease, increased food production through aquaculture is a seemingly welcome sign. However, as production surges, aquaculture facilities increasingly rely on the heavy input of formulated feeds, antibiotics, antifungals, and agrochemicals. This review summarizes our current knowledge concerning major chemical, biological and emerging agents that are employed in modern aquaculture facilities and their potential impacts on public health. Findings from this review indicate that current aquaculture practices can lead to elevated levels of antibiotic residues, antibiotic-resistant bacteria, persistent organic pollutants, metals, parasites, and viruses in aquacultured finfish and shellfish. Specific populations at risk of exposure to these contaminants include individuals working in aquaculture facilities, populations living around these facilities, and consumers of aquacultured food products. Additional research is necessary not only to fully understand the human health risks associated with aquacultured fish versus wild-caught fish but also to develop appropriate interventions that could reduce or prevent these risks. In order to adequately understand, address and prevent these impacts at local, national and global scales, researchers, policy makers, governments, and aquaculture industries must collaborate and cooperate in exchanging critical information and developing targeted policies that are practical, effective and enforceable.",
"title": "Aquaculture practices and potential human health risks: current knowledge and future priorities."
},
{
"docid": "MED-2518",
"text": "Aging is not and cannot be programmed. Instead, aging is a continuation of developmental growth, driven by genetic pathways such as mTOR. Ironically, this is often misunderstood as a sort of programmed aging. In contrast, aging is a purposeless quasi-program or, figuratively, a shadow of actual programs. “The brightest flame casts the darkest shadow.” -George Martin",
"title": "Aging is not programmed"
},
{
"docid": "MED-2493",
"text": "There is now compelling evidence that developmental exposure to chemicals from our environment contributes to disease later in life, with animal models supporting this concept in reproductive, metabolic, and neurodegenerative diseases. In contrast, data regarding how developmental exposures impact the susceptibility of the immune system to functional alterations later in life are surprisingly scant. Given that the immune system forms an integrated network that detects and destroys invading pathogens and cancer cells, it provides the body’s first line of defense. Thus, the consequences of early-life exposures that reduce immune function are profound. This review summarizes available data for pollutants such as cigarette smoke and dioxin-like compounds, which consistently support the idea that developmental exposures critically impact the immune system. These findings suggest that exposure to common chemicals from our daily environment represent overlooked contributors to the fact that infectious diseases remain among the top five causes of death worldwide.",
"title": "Environmental toxicants and the developing immune system: a missing link in the global battle against infectious disease?"
},
{
"docid": "MED-923",
"text": "The effects of glucocorticoid on lipid metabolism of broiler chicken (Gallus gallus domesticus) skeletal muscle were investigated. Male Arbor Acres chickens (35 days old) were subjected to dexamethasone treatment for 3 days. We found that dexamethasone retards body growth while facilitating lipid accumulation. In M. pectoralis major (PM), dexamethasone increased the expression of glucocorticoid receptor (GR), fatty acid transport protein 1 (FATP1), heart fatty acid-binding protein (H-FABP) and long-chain acyl-CoA dehydrogenase (LCAD) mRNA and decreased the expression of liver carnitine palmitoyltransferase 1 (L-CPT1), adenosine-monophosphate-activated protein kinase (AMPK) α2 and lipoprotein lipase (LPL) mRNA. LPL activity was also decreased. In M. biceps femoris (BF), the levels of GR, FATP1 and L-CPT1 mRNA were increased. AMPKα (Thr172) phosphorylation and CTP1 activity of skeletal muscle were decreased by dexamethasone. In fed chickens, dexamethasone enhanced very low-density lipoprotein receptor (VLDLR) expression and AMPK activity in muscle, but it impaired the expression of LPL and L-CPT1 mRNA and LPL activity in PM and augmented the expression of GR, LPL, H-FABP, L-CPT1, LCAD and AMPKα2 mRNA in BF. Adipose triglyceride lipase (ATGL) protein expression was not affected by dexamethasone. In conclusion, in the fasting state, dexamethasone-induced-retarded fatty acid utilisation may be involved in the augmented intramyocellular lipid accumulation in both glycolytic (PM) and oxidative (BF) muscle tissues. In the fed state, dexamethasone promoted the transcriptional activity of genes related to lipid uptake and oxidation in muscles. Unmatched lipid uptake and utilisation are suggested to be involved in the augmented intramyocellular lipid accumulation.",
"title": "Dexamethasone facilitates lipid accumulation in chicken skeletal muscle."
},
{
"docid": "MED-1763",
"text": "The current trends of increasing incidences of testis, breast and prostate cancers are poorly understood, although it is assumed that sex hormones play a role. Disrupted sex hormone action is also believed to be involved in the increased occurrence of genital abnormalities among newborn boys and precocious puberty in girls. In this article, recent literature on sex steroid levels and their physiological roles during childhood is reviewed. It is concluded that (i) circulating levels of estradiol in prepubertal children are lower than originally claimed; (ii) children are extremely sensitive to estradiol and may respond with increased growth and/or breast development even at serum levels below the current detection limits; (iii) no threshold has been established, below which no hormonal effects can be seen in children exposed to exogenous steroids or endocrine disruptors; (iv) changes in hormone levels during fetal and prepubertal development may have severe effects in adult life and (v) the daily production rates of sex steroids in children estimated by the Food and Drug Administration in 1999 and still used in risk assessments are highly overestimated and should be revised. Because no lower threshold for estrogenic action has been established, caution should be taken to avoid unnecessary exposure of fetuses and children to exogenous sex steroids and endocrine disruptors, even at very low levels.",
"title": "The sensitivity of the child to sex steroids: possible impact of exogenous estrogens."
},
{
"docid": "MED-4724",
"text": "We report on the case of an infant who was hospitalized because of failure to thrive, megaloblastic anemia, and delayed psychomotor development. He was 10 months old and had been exclusively breast-fed by his vegan mother. Investigations showed vitamin B(12) deficiency with hematocytopenia and pervasive developmental disorders as well as vitamin K and vitamin D deficiencies. The infant's mother presented the same deficiencies. Introduction of vitamin supplementation normalized the biological disorders, and the infant showed weight gain and neurological improvement. This case highlights that a vegan diet during pregnancy followed by exclusive breast-feeding can induce nutritional deficiencies in the newborn, with clinical consequences. Detecting mother and child vitamin deficiencies and preventing them is essential.",
"title": "[Consequences of exclusive breast-feeding in vegan mother newborn--case report]."
}
] |
PLAIN-2733
|
Beans and the Second Meal Effect
|
[
{
"docid": "MED-4440",
"text": "BACKGROUND: Contrary to earlier clinical studies suggesting that soy may promote breast tumor growth, two recent studies show that soy-containing foods are not adversely related to breast cancer prognosis. We examined, using data from the Women's Healthy Eating and Living (WHEL) study, the effect of soy intake on breast cancer prognosis. METHODS: Three thousand eighty-eight breast cancer survivors, diagnosed between 1991 and 2000 with early-stage breast cancer and participating in WHEL, were followed for a median of 7.3 years. Isoflavone intakes were measured postdiagnosis by using a food frequency questionnaire. Women self-reported new outcome events semiannually, which were then verified by medical records and/or death certificates. HRs and 95% CIs representing the association between either a second breast cancer event or death and soy intake were computed, adjusting for study group and other covariates, using the delayed entry Cox proportional hazards model. RESULTS: As isoflavone intake increased, risk of death decreased (P for trend = 0.02). Women at the highest levels of isoflavone intake (>16.3 mg isoflavones) had a nonsignificant 54% reduction in risk of death. CONCLUSION: Our study is the third epidemiologic study to report no adverse effects of soy foods on breast cancer prognosis. IMPACT: These studies, taken together, which vary in ethnic composition (two from the United States and one from China) and by level and type of soy consumption, provide the necessary epidemiologic evidence that clinicians no longer need to advise against soy consumption for women with a diagnosis of breast cancer. ©2011 AACR.",
"title": "Soy food consumption and breast cancer prognosis."
},
{
"docid": "MED-721",
"text": "Bismuth therapy has shown efficacy against two major gastrointestinal disorders: peptic ulcer disease and diarrhea. In peptic ulcer disease it is as effective as the H2-receptor antagonists, costs considerably less, and offers a lower rate of relapse. When Helicobacter pylori is implicated, bismuth acts as an antimicrobial agent, suppressing the organism but not eliminating it. In recent studies, bismuth compounds have been used with conventional antibiotics, producing elimination of the organism, histological improvement, and amelioration of symptoms for periods longer than one year. Bismuth subsalicylate has shown modest efficacy in treating traveler's diarrhea and acute and chronic diarrhea in children, and it is effective prophylactically for traveler's diarrhea. An epidemic of neurological toxicity was reported in France in the 1970's with prolonged bismuth treatment, usually bismuth subgallate and subnitrate. Such toxicity has been rare with bismuth subsalicylate and colloidal bismuth subcitrate. However, recent studies have demonstrated intestinal absorption of bismuth (about 0.2% of the ingested dose) and sequestration of this heavy metal in multiple tissue sites, even occurring with conventional dosing over a 6-week period. These findings have inspired recommendations that treatment periods with any bismuth-containing compound should last no longer than 6-8 weeks, followed by 8-week bismuth-free intervals.",
"title": "Bismuth therapy in gastrointestinal diseases."
},
{
"docid": "MED-4681",
"text": "BACKGROUND: It has been suggested that phytoestrogens and dietary fiber can affect puberty timing. OBJECTIVE: We examined whether intake of isoflavone and fiber in healthy white children before their pubertal growth spurt [age at take-off (ATO)] was associated with puberty timing. DESIGN: Multivariate regression analyses were performed in 227 DONALD (DOrtmund Nutritional and Anthropometric Longitudinally Designed) Study participants with 3-d weighed dietary records and information on potential confounders at baseline (1 and 2 y before ATO). In a subsample (n = 111), urinary isoflavones were determined in 24-h urine samples by gas chromatography-mass spectrometry analysis. Puberty timing was examined by using ATO and chronologic ages at pubertal stage 2 for breast development (B2) or gonadal development, peak height velocity (PHV), and menarche or voice break. RESULTS: Girls whose diet was in the highest dietary isoflavone tertile experienced Tanner stage 2 for breast development ap 0.7 y later and reached PHV ap 0.6 y later than did girls whose diet was in the lowest isoflavone tertile [age (95% CI) at B2: 10.7 y (10.4, 10.9 y) compared with 10.0 y ( 9.7, 10.3 y), respectively; P for trend = 0.04; age at PHV: 11.9 y (11.6, 12.2 y) compared with 11.3 y (11.0, 11.6 y), respectively; P for trend = 0.04; adjusted for body mass index z score and fiber intake]. In boys, dietary isoflavones were not associated with pubertal markers. Urinary isoflavone and dietary fiber intakes were not associated with pubertal markers. CONCLUSIONS: Girls, but not boys, with higher prepubertal isoflavone intakes appear to enter puberty at a later age. Fiber intake in this sample of healthy white girls and boys was not relevant for puberty timing.",
"title": "Relation of isoflavones and fiber intake in childhood to the timing of puberty."
},
{
"docid": "MED-3893",
"text": "Seven cyclists exercised at 70% of maximal O2 uptake (VO2max) until fatigue (170 +/- 9 min) on three occasions, 1 wk apart. During these trials, plasma glucose declined from 5.0 +/- 0.1 to 3.1 +/- 0.1 mM (P less than 0.001) and respiratory exchange ratio (R) fell from 0.87 +/- 0.01 to 0.81 +/- 0.01 (P less than 0.001). After resting 20 min the subjects attempted to continue exercise either 1) after ingesting a placebo, 2) after ingesting glucose polymers (3 g/kg), or 3) when glucose was infused intravenously (\"euglycemic clamp\"). Placebo ingestion did not restore euglycemia or R. Plasma glucose increased (P less than 0.001) initially to approximately 5 mM and R rose (P less than 0.001) to approximately 0.83 with glucose infusion or carbohydrate ingestion. Plasma glucose and R then fell gradually to 3.9 +/- 0.3 mM and 0.81 +/- 0.01, respectively, after carbohydrate ingestion but were maintained at 5.1 +/- 0.1 mM and 0.83 +/- 0.01, respectively, by glucose infusion. Time to fatigue during this second exercise bout was significantly longer during the carbohydrate ingestion (26 +/- 4 min; P less than 0.05) or glucose infusion (43 +/- 5 min; P less than 0.01) trials compared with the placebo trial (10 +/- 1 min). Plasma insulin (approximately 10 microU/ml) and vastus lateralis muscle glycogen (approximately 40 mmol glucosyl U/kg) did not change during glucose infusion, with three-fourths of total carbohydrate oxidation during the second exercise bout accounted for by the euglycemic glucose infusion rate (1.13 +/- 0.08 g/min).(ABSTRACT TRUNCATED AT 250 WORDS)",
"title": "Reversal of fatigue during prolonged exercise by carbohydrate infusion or ingestion."
},
{
"docid": "MED-724",
"text": "In addition to causing embarrassment and unease, flatulence is linked to a variety of symptoms, some of which may be distressing. This review describes the origins of intestinal gas, its composition and methods which have been developed for its analysis. Emphasis is placed upon the effects of legumes in the diet in producing excessive intestinal gas and, particularly, on the role of raffinose-type oligosaccharides, containing alpha-galactosidic groupings. Suggestions for overcoming the problem are presented, including drug treatment, enzyme treatment, food processing and plant breeding. It is emphasised that removal of all raffinose-oligosaccharides from beans does not remove the problem of flatulence in animals and man; the compounds responsible--though assumed to be polysaccharides (or polysaccharide-derived oligomers formed by processing or cooking)--have yet to be characterised.",
"title": "Flatulence--causes, relation to diet and remedies."
},
{
"docid": "MED-720",
"text": "Bloating, abdominal distention, and flatulence represent very frequent complaints in functional disorders but their pathophysiology and treatment are largely unknown. Patients frequently associate these symptoms with excessive intestinal gas and the reduction of gas production may represent an effective strategy. The aim was to evaluate the effect of alpha-galactosidase administration, in a randomized double-blind placebo-controlled protocol, on intestinal gas production and gas-related symptoms after a challenge test meal in healthy volunteers. Eight healthy volunteers ingested 300 or 1200 GalU of alpha-galactosidase or placebo during a test meal containing 420 g of cooked beans. Breath hydrogen excretion and occurrence of bloating, abdominal pain, discomfort, flatulence, and diarrhea were measured for 8 hr. The administration of 1200 GalU of alpha-galactosidase induced a significant reduction of both breath hydrogen excretion and severity of flatulence. A reduction in severity was apparent for all considered symptoms, but both 300 and 1200 GalU induced a significant reduction in the total symptom score. Alpha-galactosidase reduced gas production following a meal rich in fermentable carbohydrates and may be helpful in patients with gas-related symptoms.",
"title": "The effect of oral alpha-galactosidase on intestinal gas production and gas-related symptoms."
},
{
"docid": "MED-4863",
"text": "Chemical and cellular antioxidant activities and phenolic profiles of 11 lentil cultivars grown in the cool northern parts of the United States were investigated. Individual phenolic compounds, including phenolic acids, flavan-3-ols, flavones, and anthocyanins, were further quantitatively investigated by HPLC. Cellular antioxidant activities (CAA) and peroxyl radical scavenging capacity (PRSC) were evaluated by fluorescence microplate reader. Cultivar Morton exhibited the highest individual flavan-3-ols (catechin and epicatechin) and total flavonoids, as well as the highest antioxidant properties (PRSC and CAA) among all lentils tested. Five phenolic acids of the benzoic types and their derivates (gallic, protocatechuic, 2,3,4-trihydroxybenzoic, p-hydroxybenzoic acid, and protocatechualdehyde) and four phenolic acids of the cinnamic type (chlorogenic, p-coumaric, m-coumaric, and sinapic acid) were detected in all lentil cultivars. Two flavan-3-ols [(+)-catechin and (-)-epicatechin] and one flavone (luteolin) were detected in all lentil cultivars. Among all phenolic compounds detected, sinapic acid was the predominant phenolic acid, and (+)-catechin and (-)-epicatechin were the predominant flavonoids. These results showed that different phenotype lentils possessed considerable variations in their individual phenolic compounds, as well as chemical and cellular antioxidant activities. Caffeic acid, catechin, epicatechin, and total flavonoids significantly (p < 0.05) correlated with peroxyl radical scavenging assay. Cellular antioxidant assay significantly correlated with chemical antioxidant assay ORAC. The results from this study could be very interesting for breeding programs to improve lentils for use as functional foods.",
"title": "Phenolic substance characterization and chemical and cell-based antioxidant activities of 11 lentils grown in the northern United States."
},
{
"docid": "MED-722",
"text": "Complaints of \"excessive gas\" from patients are very common but are difficult, if not impossible, for the physician to document. This review addresses the pathophysiology and management of such complaints, looking at the sources and routes of elimination, excessive eructation, bloating, and distention. In addition, common flatulence problems are summarized, including excessive flatus volume and noxious flatus.",
"title": "An understanding of excessive intestinal gas."
},
{
"docid": "MED-4768",
"text": "The rapid increase in obesity and the associated health care costs have prompted a search for better approaches for its prevention and management. Such efforts may be facilitated by better understanding the etiology of obesity. Of the several etiological factors, infection, an unusual causative factor, has recently started receiving greater attention. In the last two decades, 10 adipogenic pathogens were reported, including human and nonhuman viruses, scrapie agents, bacteria, and gut microflora. Some of these pathogens are associated with human obesity, but their causative role in human obesity has not been established. This chapter presents information about the natural hosts, signs and symptoms, and pathogenesis of the adipogenic microorganisms. If relevant to humans, \"Infectobesity\" would be a relatively novel, yet extremely significant concept. A new perspective about the infectious etiology of obesity may stimulate additional research to assess the contribution of hitherto unknown pathogens to human obesity and possibly to prevent or treat obesity of infectious origins.",
"title": "Infectobesity: obesity of infectious origin."
},
{
"docid": "MED-4509",
"text": "Hypercholesterolemia is a major modifiable risk factor for cardiovascular disease. Some, but not all, studies have shown that soy protein intake decreases total and low-density lipoprotein cholesterol and triglycerides and increases high-density lipoprotein cholesterol. The objective of this meta-analysis was to examine the effect of soy protein supplementation on serum lipid levels in adults. English language articles were retrieved by searching MEDLINE (1966 to February 2005) and the bibliographies of the retrieved articles. A total of 41 randomized controlled trials in which isolated soy protein supplementation was the only intervention and the net changes in serum lipids during intervention were reported. Information on study design, sample size, participant characteristics, intervention, follow-up duration, and treatment outcomes was independently abstracted using a standardized protocol. Using a random-effects model, data from each study were pooled and weighted by the inverse of their variance. Soy protein supplementation was associated with a significant reduction in mean serum total cholesterol (-5.26 mg/dl, 95% confidence interval [CI] -7.14 to -3.38), low-density lipoprotein cholesterol (-4.25 mg/dl, 95% CI -6.00 to -2.50), and triglycerides (-6.26 mg/dl, 95% CI -9.14 to -3.38) and a significant increase in high-density lipoprotein cholesterol (0.77 mg/dl, 95% CI 0.20 to 1.34). Meta-regression analyses showed a dose-response relation between soy protein and isoflavone supplementation and net changes in serum lipids. These results indicate that soy protein supplementation reduces serum lipids among adults with or without hypercholesterolemia. In conclusion, replacing foods high in saturated fat, trans-saturated fat, and cholesterol with soy protein may have a beneficial effect on coronary risk factors.",
"title": "A meta-analysis of the effect of soy protein supplementation on serum lipids."
},
{
"docid": "MED-4106",
"text": "OBJECTIVES: The objective of this study was to assess the relation between the level of habitual potassium intake and the incidence of cardiovascular disease (CVD). BACKGROUND: Prospective cohort studies have evaluated the relationship between habitual potassium intake and incidence of vascular disease, but their results have not been not entirely consistent. METHODS: We performed a systematic search for prospective studies published, without language restrictions (1966 to December 2009). Criteria for inclusion were prospective adult population study, assessment of baseline potassium intake, assessment of vascular events as outcome, and follow-up of at least 4 years. For each study, relative risks (RRs) and 95% confidence intervals (CIs) were extracted and pooled using a random-effect model, weighted for the inverse of the variance. Heterogeneity, publication bias, subgroup, and meta-regression analyses were performed. RESULTS: Eleven studies were identified, providing 15 cohort samples that included 247,510 male and female participants (follow-up 5 to 19 years), 7,066 strokes, 3,058 coronary heart disease (CHD) events, and 2,497 total CVD events. Potassium intake was assessed by 24-h dietary recall (n = 2), food frequency questionnaire (n = 6), or 24-h urinary excretion (n = 3). In the pooled analysis, a 1.64-g (42 mmol) per day higher potassium intake was associated with a 21% lower risk of stroke (RR: 0.79; 95% CI: 0.68 to 0.90; p = 0.0007), with a trend toward lower risk of CHD and total CVD that attained statistical significance after the exclusion of a single cohort, based on sensitivity analysis (RR: 0.93; 95% CI: 0.87 to 0.99; p = 0.03 and RR: 0.74; 95% CI: 0.60 to 0.91; p = 0.0037). CONCLUSIONS: Higher dietary potassium intake is associated with lower rates of stroke and might also reduce the risk of CHD and total CVD. These results support recommendations for higher consumption of potassium-rich foods to prevent vascular diseases. Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.",
"title": "Potassium intake, stroke, and cardiovascular disease a meta-analysis of prospective studies."
},
{
"docid": "MED-4678",
"text": "The aim of this study was to obtain a better understanding of the role of hormonal factors in breast cancer risk and to determine whether the effect of reproductive events differs according to age at diagnosis. It analysed the effect of age at menarche, age at first full-term pregnancy, number of full-term pregnancies and number of spontaneous abortions both on the overall risk of breast cancer and on its pre- or postmenopausal onset, using the data on 1718 breast cancer cases, obtained from a large sample of around 100 000 French women participating in the E3N cohort study. The results provide further evidence that the overall risk of breast cancer increases with decreasing age at menarche, increasing age at first pregnancy and low parity. No overall effect of spontaneous abortions was observed. The effect of these reproductive factors differed according to menopausal status. Age at menarche had an effect on premenopausal breast cancer risk, with a decrease in risk with increasing age of 7% per year (P<0.05). Compared to those who had their first menstrual periods at 11 or before, women experiencing menarche at 15 or after had an RR of 0.66 (95% CI 0.45–0.97) in the premenopausal group. Age at first full-term pregnancy had an effect on both pre- and postmenopausal breast cancer risk, with significant tests showing increasing risk per year of increasing age (P=0.001 and P<0.05 respectively). A first full-term pregnancy above age 30 conveyed a risk of 1.63 (95% CI 1.12–2.38) and 1.35 (95% CI 1.02–1.78) in the pre- and postmenopausal groups respectively. A protective effect of high parity was observed only for postmenopausal breast cancer risk (P for trend test =0.001), with point estimates of 0.79 (95% CI 0.60–1.04), 0.69 (95% CI 0.54–0.88), 0.66 (95% CI 0.51–0.85) and 0.64 (95% CI 0.48–0.86) associated to a one, two, three and four or more full-term pregnancies. A history of spontaneous abortion had no significant effect on the risk of breast cancer diagnosed before or after menopause. Our results suggest that reproductive events have complex effects on the risk of breast cancer. British Journal of Cancer (2002) 86, 723–727. DOI: 10.1038/sj/bjc/6600124 www.bjcancer.com © 2002 Cancer Research UK",
"title": "Differential effects of reproductive factors on the risk of pre- and postmenopausal breast cancer. Results from a large cohort of French women"
},
{
"docid": "MED-4679",
"text": "OBJECTIVES The objective of this study was to describe the assessment methods and maturation status for a multisite cohort of girls at baseline recruitment and at ages 7 and 8 years. METHODS The method for pubertal maturation staging was developed collaboratively across 3 sites. Girls at ages 6 to 8 years were recruited at 3 sites: East Harlem, New York; greater Cincinnati metropolitan area; and San Francisco Bay area, California. Baseline characteristics were obtained through interviews with caregivers and anthropometric measurements by trained examiners; breast stage 2 was defined as onset of pubertal maturation. The κ statistic was used to evaluate agreement between master trainers and examiners. Logistic regression models were used to identify factors that are associated with pubertal maturation and linear regression models to examine factors that are associated with height velocity. RESULTS The baseline cohort included 1239 girls. The proportion of girls who had attained breast stage 2 varied by age, race/ethnicity, BMI percentile, and site. At 7 years, 10.4% of white, 23.4% of black non-Hispanic, and 14.9% of Hispanic girls had attained breast stage ≥2; at 8 years, 18.3%, 42.9%, and 30.9%, respectively, had attained breast stage ≥2. The prime determinant of height velocity was pubertal status. CONCLUSIONS In this multisite study, there was substantial agreement regarding pubertal staging between examiners across sites. The proportion of girls who had breast development at ages 7 and 8 years, particularly among white girls, is greater than that reported from studies of girls who were born 10 to 30 years earlier.",
"title": "Pubertal Assessment Method and Baseline Characteristics in a Mixed Longitudinal Study of Girls"
},
{
"docid": "MED-3584",
"text": "Background: A high intake of white rice is associated with the metabolic syndrome and type 2 diabetes. Costa Ricans follow a staple dietary pattern that includes white rice and beans, yet the combined role of these foods on cardiometabolic risk factors has not been studied. Objective: We aimed to determine the association between intake of white rice and beans and the metabolic syndrome and its components in Costa Rican adults (n = 1879) without diabetes. Design: Multivariate-adjusted means were calculated for components of the metabolic syndrome by daily servings of white rice and beans (<1, 1, or >1) and by the ratio of beans to white rice. The OR for the metabolic syndrome was calculated by substituting one serving of beans for one serving of white rice. Results: An increase in daily servings of white rice was positively associated with systolic blood pressure (BP), triglycerides, and fasting glucose and inversely associated with HDL cholesterol (P-trend <0.01 for all). An increase in servings of beans was inversely associated with diastolic BP (P = 0.049). Significant trends for higher HDL cholesterol and lower BP and triglycerides were observed for 1:3, 1:2, 1:1, and 2:1 ratios of beans to white rice. Substituting one serving of beans for one serving of white rice was associated with a 35% (95% CI: 15%, 50%) lower risk of the metabolic syndrome. Conclusion: Increasing the ratio of beans to white rice, or limiting the intake of white rice by substituting beans, may lower cardiometabolic risk factors.",
"title": "A higher ratio of beans to white rice is associated with lower cardiometabolic risk factors in Costa Rican adults"
},
{
"docid": "MED-5322",
"text": "BACKGROUND/AIMS: This study aimed to investigate the quantitative and qualitative changes of bacteria, Bacteroides, Bifidobacterium and Clostridium cluster IV in faecal microbiota associated with a vegetarian diet. METHODS: Bacterial abundances were measured in faecal samples of 15 vegetarians and 14 omnivores using quantitative PCR. Diversity was assessed with PCR-DGGE fingerprinting, principal component analysis (PCA) and Shannon diversity index. RESULTS: Vegetarians had a 12% higher abundance of bacterial DNA than omnivores, a tendency for less Clostridium cluster IV (31.86 +/- 17.00%; 36.64 +/- 14.22%) and higher abundance of Bacteroides (23.93 +/- 10.35%; 21.26 +/- 8.05%), which were not significant due to high interindividual variations. PCA suggested a grouping of bacteria and members of Clostridium cluster IV. Two bands appeared significantly more frequently in omnivores than in vegetarians (p < 0.005 and p < 0.022). One was identified as Faecalibacterium sp. and the other was 97.9% similar to the uncultured gut bacteriumDQ793301. CONCLUSIONS: A vegetarian diet affects the intestinal microbiota, especially by decreasing the amount and changing the diversity of Clostridium cluster IV. It remains to be determined how these shifts might affect the host metabolism and disease risks. Copyright 2009 S. Karger AG, Basel.",
"title": "Characterization of bacteria, clostridia and Bacteroides in faeces of vegetarians using qPCR and PCR-DGGE fingerprinting."
},
{
"docid": "MED-4600",
"text": "Enough solid evidence now exists to offer women several fundamental strategies for healthy eating. They include emphasizing healthful unsaturated fats, whole grains, good protein “packages,” and fruits and vegetables; limiting consumption of trans and saturated fats, highly refined grains, and sugary beverages; and taking a multivitamin with folic acid and extra vitamin D as a nutritional safety net. A diet based on these principles is healthy through virtually all life stages, from young adulthood through planning for pregnancy, pregnancy, and on into old age.",
"title": "Essentials of Healthy Eating: A Guide"
},
{
"docid": "MED-3895",
"text": "Research suggests that pre-exercise sources of dietary carbohydrate with varying glycemic indexes may differentially affect metabolism and endurance. This study was designed to examine potential differences in metabolism and cycling performance after consumption of moderate glycemic raisins vs. a high glycemic commercial sports gel. Eight endurance-trained male (n = 4) and female (n = 4) cyclists 30 +/- 5 years of age completed 2 trials in random order. Subjects were fed 1 g carbohydrate per kilogram body weight from either raisins or sports gel 45 minutes prior to exercise on a cycle ergometer at 70% V(.-)O2max. After 45 minutes of submaximal exercise, subjects completed a 15-minute performance trial. Blood was collected prior to the exercise bout, as well as after the 45th minute of exercise, to determine serum concentrations of glucose, insulin, lactate, free fatty acids (FFAs), triglycerides, and beta-hydroxybutyrate. Performance was not different (p > 0.05) between the raisin (189.5 +/- 69.9 kJ) and gel (188.0 +/- 64.8 kJ) trials. Prior to exercise, serum concentrations of glucose and other fuel substrates did not differ between trials; however, insulin was higher (p < 0.05) for the gel (110.0 +/- 70.4 microU x ml(-1)) vs. raisin trial (61.4 +/- 37.4 microU x ml(-1)). After 45 minutes of exercise, insulin decreased to 14.2 +/- 6.2 microU x ml(-1) and 13.3 +/- 18.9 microU x ml(-1) for gel and raisin trials, respectively. The FFA concentration increased (+0.2 +/- 0.1 mmol x L(-1)) significantly (p < 0.05) during the raisin trial. Overall, minor differences in metabolism and no difference in performance were detected between the trials. Raisins appear to be a cost-effective source of carbohydrate for pre-exercise feeding in comparison to sports gel for short-term exercise bouts.",
"title": "Metabolic and performance effects of raisins versus sports gel as pre-exercise feedings in cyclists."
},
{
"docid": "MED-718",
"text": "OBJECTIVE: To determine the relation of gas passage and abdominal bloating to the production of gas in the colon. DESIGN: Randomized, double-blind, crossover study of gaseous symptoms during a 1-week period. SETTING: A Veterans Affairs medical center. PARTICIPANTS: 25 healthy medical center employees. INTERVENTION: Participants' diets were supplemented with either a placebo (10 g of lactulose, a nonabsorbable sugar), psyllium (a fermentable fiber), or methylcellulose (a nonfermentable fiber). MEASUREMENTS: All participants were polled for gaseous symptoms (including number of gas passages, impression of increased rectal gas, and abdominal bloating), and five were examined for breath hydrogen excretion. RESULTS: Participants passed gas 10 +/- 5.0 times per day (mean +/- SD) during the placebo period. A significant increase in gas passages (to 19 +/- 12 times per day) and a subjective impression of increased rectal gas were reported with lactulose but not with either of the two fiber preparations. Breath hydrogen excretion, an indicator of hydrogen production in the colon, did not increase after ingestion of either of the fibers. However, a statistically significant (P < 0.05) increase in feelings of abdominal bloating (which the participants perceived as excessive gas in the bowel) was reported with both fiber preparations and with lactulose. CONCLUSIONS: The physician should distinguish between excessive gas (which indicates excessive gas production) and feelings of bloating (which are usually unrelated to excessive gas production). Treatment of the former consists of limiting the supply of fermentable material to the colonic bacteria. Symptoms of bloating usually indicate the irritable bowel syndrome, and therapy should be directed accordingly.",
"title": "The relation of passage of gas an abdominal bloating to colonic gas production."
},
{
"docid": "MED-4785",
"text": "Purpose Soy isoflavones, structurally similar to endogenous estrogens, may affect breast cancer through both hormonally-mediated and non-hormonally related mechanisms. Although the effects of soy are not well understood, some breast cancer survivors increase their soy intake post-diagnosis in attempt to improve their prognosis. Therefore, we examined the role of soy isoflavone intake and the risk of breast cancer recurrence by hormone receptor status, menopausal status, and tamoxifen therapy. Materials and methods A cohort of 1954 female breast cancer survivors, diagnosed during 1997–2000, was prospective followed for 6.31 years and 282 breast cancer recurrences were ascertained. Isoflavone intake was assessed by mailing modified Block and supplemental soy food frequency questionnaires to participants, on average 23 months post-diagnosis. Risk of breast cancer recurrence, measured by hazard ratios (HR) and 95% confidence intervals (CI), was estimated using multivariable delayed-entry Cox proportional hazards models. Results Suggestive trends for a reduced risk of cancer recurrence were observed with increasing quintiles of daidzein and glycetin intake compared to no intake among postmenopausal women (P for trend: P = .08 for daidzein, P = .06 for glycetin) and among tamoxifen users (P = .10 for daidzein, P = .05 for glycetin). Among postmenopausal women treated with tamoxifen, there was an approximately 60% reduction in breast cancer recurrence comparing the highest to the lowest daidzein intakes (>1453 micrograms (µg)/day versus < 7.7 µg/day) (HR, 0.48; 95% CI, 0.21–0.79, P = .008). Conclusion Soy isoflavones consumed at levels comparable to those in Asian populations may reduce the risk of cancer recurrence in women receiving tamoxifen therapy and moreover, appears not to interfere with tamoxifen efficacy. Further confirmation is required in other large prospective studies before recommendations regarding soy intake can be issued to breast cancer survivors.",
"title": "Soy Isoflavones and Risk of Cancer Recurrence in a Cohort of Breast Cancer Survivors: Life After Cancer Epidemiology (LACE) Study"
},
{
"docid": "MED-3583",
"text": "Pulses are low-glycemic appetite-suppressing foods, but it is not known whether these properties persist after being consumed as part of a meal and after a second meal. The objective of this study was to determine the effects of a fixed-size pulse meal on appetite and blood glucose (BG) before and after an ad libitum test meal (pizza) and on food intake (FI) at the test meal. Males (n = 25; 21.3 ± 0.5 years; 21.6 ± 0.3 kg·m(-2)) randomly consumed 4 isocaloric meals: chickpea; lentil; yellow split pea; and macaroni and cheese (control). Commercially available canned pulses provided 250 kcal, and were consumed with macaroni and tomato sauce. FI was measured at a pizza meal 260 min after consumption of the isocaloric meal. BG and appetite were measured from 0 to 340 min. The lentil and yellow pea, but not chickpea, treatments led to lower appetite ratings during the 260 min prepizza meal period, and less FI at the pizza meal, compared with macaroni and cheese (p < 0.05). All pulse treatments lowered BG immediately following consumption (at 20 min) (p < 0.05), but there was no effect of treatment on prepizza meal BG AUC (p = 0.07). Immediately after the pizza meal, BG was lower following the chickpea and lentil treatments, but not the yellow pea treatment (p < 0.05). Postpizza meal BG AUC was lower following the chickpea and lentil treatments than in the yellow pea treatment (p < 0.05). The beneficial effects of consuming a pulse meal on appetite, FI at a later meal, and the BG response to a later meal are dependent on pulse type.",
"title": "First and second meal effects of pulses on blood glucose, appetite, and food intake at a later meal."
},
{
"docid": "MED-3580",
"text": "The effects of the glycemic index (GI) of carbohydrate eaten the previous night on the glycemic response to a standard test meal eaten subsequently in the morning (breakfast) was studied. On separate evenings normal subjects ate low- or high-GI test meals of the same nutrient composition. The dinners consisted of single foods in two experiments and mixed meals containing several foods in the third. The differences between the observed glycemic responses to low- and high-GI dinners were predicted by their GIs. The glycemic responses to breakfast were significantly lower on mornings after low-GI dinners than after high-GI dinners. Eating, at dinner, foods with different fiber contents but the same GI had no effect on postbreakfast glycemia. We conclude that the GI predicts the difference between glycemic responses of mixed dinner meals; breakfast carbohydrate tolerance is improved when low-GI foods are eaten the previous evening.",
"title": "Second-meal effect: low-glycemic-index foods eaten at dinner improve subsequent breakfast glycemic response."
},
{
"docid": "MED-4917",
"text": "AIMS: To review current research on the effects of soy consumption on menopausal symptoms. METHODS: To review results of recent meta-analyses and individual clinical trials. MAIN RESULTS: One recent meta-analysis reported that isoflavone supplementation was associated with a 34% reduction in hot flashes, with increased efficacy as the baseline number of flashes and isoflavone dose increased. A second review concluded that consumption of at least 15 mg genistein, rather than total isoflavones, is responsible for the reduction in symptoms. Results of these two reviews are supported by most subsequent randomized controlled trials. CONCLUSIONS: Consumption of 30 mg/day of soy isoflavones (or at least 15 mg genistein) reduces hot flashes by up to 50 %. This total reduction includes that provided by \"the placebo effect\". The greatest benefit may be realized when the isoflavone-rich food or supplement is taken in divided doses by subjects who experience at least four hot flashes/day.",
"title": "Soy consumption for reduction of menopausal symptoms."
},
{
"docid": "MED-4271",
"text": "Dietary fibres are indigestible food ingredients that reach the colon and are then fermented by colonic bacteria, resulting mainly in the formation of short-chain fatty acids (SCFA) such as acetate, propionate, and butyrate. Those SCFA, especially butyrate, are recognised for their potential to act on secondary chemoprevention by slowing growth and activating apoptosis in colon cancer cells. Additionally, SCFA can also act on primary prevention by activation of different drug metabolising enzymes. This can reduce the burden of carcinogens and, therefore, decrease the number of mutations, reducing cancer risk. Activation of GSTs by butyrate has been studied on mRNA, protein, and enzyme activity level by real-time RT-PCR, cDNA microarrays, Western blotting, or photometrical approaches, respectively. Butyrate had differential effects in colon cells of different stages of cancer development. In HT29 tumour cells, e.g., mRNA GSTA4, GSTP1, GSTM2, and GSTT2 were induced. In LT97 adenoma cells, GSTM3, GSTT2, and MGST3 were induced, whereas GSTA2, GSTT2, and catalase (CAT) were elevated in primary colon cells. Colon cells of different stages of carcinogenesis differed in post-transcriptional regulatory mechanisms because butyrate increased protein levels of different GST isoforms and total GST enzyme activity in HT29 cells, whereas in LT97 cells, GST protein levels and activity were slightly reduced. Because butyrate increased histone acetylation and phosphorylation of ERK in HT29 cells, inhibition of histone deacetylases and the influence on MAPK signalling are possible mechanisms of GST activation by butyrate. Functional consequences of this activation include a reduction of DNA damage caused by carcinogens like hydrogen peroxide or 4-hydroxynonenal (HNE) in butyrate-treated colon cells. Treatment of colon cells with the supernatant from an in vitro fermentation of inulin increased GST activity and decreased HNE-induced DNA damage in HT29 cells. Additional animal and human studies are needed to define the exact role of dietary fibre and butyrate in inducing GST activity and reducing the risk of colon cancer.",
"title": "Mechanisms of primary cancer prevention by butyrate and other products formed during gut flora-mediated fermentation of dietary fibre."
},
{
"docid": "MED-723",
"text": "OBJECTIVE: A variety of charcoal-containing devices are purported to minimize problems with odoriferous rectal gas; however, the evidence supporting the efficacy of these products is virtually all anecdotal. We objectively evaluated the ability of these devices to adsorb two malodorous, sulfide gases (hydrogen sulfide and methylmercaptan) instilled at the anus. METHODS: Via a tube, 100 ml of nitrogen containing 40 ppm of sulfide gases and 0.5% H(2) was instilled at the anus of six healthy volunteers who wore gas impermeable Mylar pantaloons over their garments. Since H(2) is not adsorbed by charcoal, the fraction of the sulfide gases removed could be determined from the concentration ratio of sulfide gas: H(2) in the pantaloon space relative to the ratio in instilled gas. RESULTS: Measurements with no device in place showed that subjects' garments removed 22.0 +/- 5.3% of the sulfide gases, and results obtained with each device were corrected for this removal. The only product that adsorbed virtually all of the sulfide gases was briefs constructed from an activated carbon fiber fabric. Pads worn inside the underwear removed 55-77% of the sulfide gases. Most cushions were relatively ineffective, adsorbing about 20% of the gases. CONCLUSIONS: The ability of charcoal-containing devices to adsorb odoriferous rectal gases is limited by incomplete exposure of the activated carbon to the gases. Briefs made from carbon fiber are highly effective; pads are less effective, removing 55-77% of the odor; cushions are relatively ineffective.",
"title": "Effectiveness of devices purported to reduce flatus odor."
},
{
"docid": "MED-717",
"text": "OBJECTIVE: Fructose intake has increased considerably in the United States, primarily as a result of increased consumption of high-fructose corn syrup, fruits and juices, and crystalline fructose. The purpose was to determine how often fructose, in amounts commonly consumed, would result in malabsorption and/or symptoms in healthy persons. DESIGN: Fructose absorption was measured using 3-hour breath hydrogen tests and symptom scores were used to rate subjective responses for gas, borborygmus, abdominal pain, and loose stools. SUBJECTS/SETTING: The study included 15 normal, free-living volunteers from a medical center community and was performed in a gastrointestinal specialty clinic. INTERVENTION: Subjects consumed 25- and 50-g doses of crystalline fructose with water after an overnight fast on separate test days. MAIN OUTCOME MEASURES: Mean peak breath hydrogen, time of peak, area under the curve (AUC) for breath hydrogen and gastrointestinal symptoms were measured during a 3-hour period after subjects consumed both 25- and 50-g doses of fructose. STATISTICAL ANALYSES: Differences in mean breath hydrogen, AUC, and symptom scores between doses were analyzed using paired t tests. Correlations among peak breath hydrogen, AUC, and symptoms were also evaluated. RESULTS: More than half of the 15 adults tested showed evidence of fructose malabsorption after 25 g fructose and greater than two thirds showed malabsorption after 50 g fructose. AUC, representing overall breath hydrogen response, was significantly greater after the 50-g dose. Overall symptom scores were significantly greater than baseline after each dose, but scores were only marginally greater after 50 g than 25 g. Peak hydrogen levels and AUC were highly correlated, but neither was significantly related to symptoms. CONCLUSIONS: Fructose, in amounts commonly consumed, may result in mild gastrointestinal distress in normal people. Additional study is warranted to evaluate the response to fructose-glucose mixtures (as in high-fructose corn syrup) and fructose taken with food in both normal people and those with gastrointestinal dysfunction. Because breath hydrogen peaks occurred at 90 to 114 minutes and were highly correlated with 180-minute breath hydrogen AUC, the use of peak hydrogen measures may be considered to shorten the duration of the exam.",
"title": "Fructose intake at current levels in the United States may cause gastrointestinal distress in normal adults."
},
{
"docid": "MED-4278",
"text": "OBJECTIVE: To describe the lifestyle characteristics and nutrient intakes of the Oxford cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC). DESIGN: Cohort of men and women recruited through general practices or by post to include a high proportion of non meat-eaters. Dietary, anthropometric and lifestyle data were collected at baseline and four diet groups were defined. SETTING: United Kingdom. PARTICIPANTS: In total, 65 429 men and women aged 20 to 97 years, comprising 33 883 meat-eaters, 10 110 fish-eaters, 18 840 lacto-ovo vegetarians and 2596 vegans. RESULTS: Nutrient intakes and lifestyle factors differed across the diet groups, with striking differences between meat-eaters and vegans, and fish-eaters and vegetarians usually having intermediate values. Mean fat intake in each diet group was below the UK dietary reference value of 33% of total energy intake. The mean intake of saturated fatty acids in vegans was approximately 5% of energy, less than half the mean intake among meat-eaters (10-11%). Vegans had the highest intakes of fibre, vitamin B1, folate, vitamin C, vitamin E, magnesium and iron, and the lowest intakes of retinol, vitamin B12, vitamin D, calcium and zinc. CONCLUSIONS: The EPIC-Oxford cohort includes 31 546 non meat-eaters and is one of the largest studies of vegetarians in the world. The average nutrient intakes in the whole cohort are close to those currently recommended for good health. Comparisons of the diet groups show wide ranges in the intakes of major nutrients such as saturated fat and dietary fibre. Such variation should increase the ability of the study to detect associations of diet with major cancers and causes of death.",
"title": "EPIC-Oxford: lifestyle characteristics and nutrient intakes in a cohort of 33 883 meat-eaters and 31 546 non meat-eaters in the UK."
},
{
"docid": "MED-5323",
"text": "This study reviewed the literature on the relations between exposure to chemicals with endocrine-disrupting abilities and obesity in humans. The studies generally indicated that exposure to some of the endocrine-disrupting chemicals was associated with an increase in body size in humans. The results depended on the type of chemical, exposure level, timing of exposure and gender. Nearly all the studies investigating dichlorodiphenyldichloroethylene (DDE) found that exposure was associated with an increase in body size, whereas the results of the studies investigating polychlorinated biphenyl (PCB) exposure were depending on dose, timing and gender. Hexachlorobenzene, polybrominated biphenyls, beta-hexachlorocyclohexane, oxychlordane and phthalates were likewise generally associated with an increase in body size. Studies investigating polychlorinated dibenzodioxins and polychlorinated dibenzofurans found either associations with weight gain or an increase in waist circumference, or no association. The one study investigating relations with bisphenol A found no association. Studies investigating prenatal exposure indicated that exposure in utero may cause permanent physiological changes predisposing to later weight gain. The study findings suggest that some endocrine disruptors may play a role for the development of the obesity epidemic, in addition to the more commonly perceived putative contributors. © 2011 The Authors. obesity reviews © 2011 International Association for the Study of Obesity.",
"title": "Endocrine-disrupting chemicals and obesity development in humans: a review."
},
{
"docid": "MED-4276",
"text": "Propionate is produced along with acetate and butyrate as a result of fermentative activity of gut microflora on dietary fiber. It has long been known to exhibit hypophagic effects in ruminants, however, its potential physiological roles in non-ruminants as well as humans remained unnoticed over the years. In view of various studies pointing towards the hypophagic as well as hypocholesterolemic effects of propionate in humans, it may act as an important factor in amelioration of obesity, a lifestyle disease arising due to energy imbalance and growing at a startling rate globally. Short chain fatty acids have recently been ascribed as ligands to G-protein coupled receptors (GPRs) 41 and 43. Thus, propionate along with acetate may also be involved in the regulation of adipogenesis and adipokine release mediated via GPRs. The present review summarizes the evidence which collectively raise the possibility of propionate as a dietary factor to depress appetite and combat the obesity epidemic. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Propionate. Anti-obesity and satiety enhancing factor?"
},
{
"docid": "MED-4269",
"text": "PURPOSE OF REVIEW: High-fiber diets have been shown to reduce plasma concentrations of inflammation markers. Increased production of fermentation-derived short-chain fatty acids (SCFAs) is one of the factors that could exert these positive effects. This review examines the effects of SCFAs on immune cells and discusses the relevance of their effects on systemic inflammation, as frequently seen in obesity. RECENT FINDINGS: SCFAs have been shown to reduce chemotaxis and cell adhesion; this effect is dependent on type and concentration of SCFA. In spite of conflicting results, especially butyrate seems to have an anti-inflammatory effect, mediated by signaling pathways like nuclear factor-κB and inhibition of histone deacetylase. The discrepancies in the results could be explained by differences in cell types used and their proliferative and differentiation status. SUMMARY: SCFAs show anti-inflammatory effects and seem to have the potency to prevent infiltration of immune cells from the bloodstream in, for example, the adipose tissue. In addition, their ability to inhibit the proliferation and activation of T cells and to prevent adhesion of antigen-presenting cells could be important as it recently has been shown that obesity-associated inflammation might be antigen-dependent. More studies with concentrations in micromolar range are needed to approach more physiological concentrations.",
"title": "Butyrate and other short-chain fatty acids as modulators of immunity: what relevance for health?"
},
{
"docid": "MED-4313",
"text": "BACKGROUND: Population-based studies have shown that vegetarians have lower body mass index than nonvegetarians, suggesting that vegetarian diet plans may be an approach for weight management. However, a perception exists that vegetarian diets are deficient in certain nutrients. OBJECTIVE: To compare dietary quality of vegetarians, nonvegetarians, and dieters, and to test the hypothesis that a vegetarian diet would not compromise nutrient intake when used to manage body weight. DESIGN: Cross-sectional analysis of National Health and Nutrition Examination Survey (1999-2004) dietary and anthropometric data. Diet quality was determined using United States Department of Agriculture's Healthy Eating Index 2005. Participants included adults aged 19 years and older, excluding pregnant and lactating women (N = 13,292). Lacto-ovo vegetarian diets were portrayed by intakes of participants who did not eat meat, poultry, or fish on the day of the survey (n = 851). Weight-loss diets were portrayed by intakes of participants who consumed 500 kcal less than their estimated energy requirements (n = 4,635). Mean nutrient intakes and body mass indexes were adjusted for energy, sex, and ethnicity. Using analysis of variance, all vegetarians were compared to all nonvegetarians, dieting vegetarians to dieting nonvegetarians, and nondieting vegetarians to nondieting nonvegetarians. RESULTS: Mean intakes of fiber, vitamins A, C, and E, thiamin, riboflavin, folate, calcium, magnesium, and iron were higher for all vegetarians than for all nonvegetarians. Although vegetarian intakes of vitamin E, vitamin A, and magnesium exceeded that of nonvegetarians (8.3 ± 0.3 vs 7.0 ± 0.1 mg; 718 ± 28 vs 603 ± 10 μg; 322 ± 5 vs 281 ± 2 mg), both groups had intakes that were less than desired. The Healthy Eating Index score did not differ for all vegetarians compared to all nonvegetarians (50.5 ± 0.88 vs 50.1 ± 0.33, P = 0.6). CONCLUSIONS: These findings suggest that vegetarian diets are nutrient dense, consistent with dietary guidelines, and could be recommended for weight management without compromising diet quality. Copyright © 2011 American Dietetic Association. Published by Elsevier Inc. All rights reserved.",
"title": "A vegetarian dietary pattern as a nutrient-dense approach to weight management: an analysis of the national health and nutrition examination survey..."
},
{
"docid": "MED-5333",
"text": "BACKGROUND/AIM: A vegetarian diet is known to prevent a series of diseases but may influence the balance of carbohydrate and fat metabolism as well as collagen synthesis. This study compares expression patterns of relevant genes in oral mucosa of omnivores and vegetarians. METHODS: Quantitative reverse transcriptase polymerase chain reaction was applied for analysis of mRNA levels from carnitine transporter OCTN2, hepatic CPT1A and nonhepatic CPT1B isoforms of carnitine palmitoyltransferase and collagen (CCOL2A1) in oral mucosa. RESULTS: Compared with volunteers with traditional eating habits, carbohydrate consumption was significantly higher (+22%) in vegetarians. This was associated with a significant stimulation of CPT1A (+50%) and OCTN2 (+10%) and a lowered collagen synthesis (-10%). CONCLUSION: These novel findings provide further insight into the association of a changed fat metabolism and reduced collagen synthesis in vegetarians, which could also play a role in the aging process. Copyright 2008 S. Karger AG, Basel.",
"title": "Vegetarian diet affects genes of oxidative metabolism and collagen synthesis."
},
{
"docid": "MED-5332",
"text": "The gastrointestinal microbiota produces short-chain fatty acids, especially butyrate, which affect colonic health, immune function and epigenetic regulation. To assess the effects of nutrition and aging on the production of butyrate, the butyryl-CoA:acetate CoA-transferase gene and population shifts of Clostridium clusters lV and XlVa, the main butyrate producers, were analysed. Faecal samples of young healthy omnivores (24 ± 2.5 years), vegetarians (26 ± 5 years) and elderly (86 ± 8 years) omnivores were evaluated. Diet and lifestyle were assessed in questionnaire-based interviews. The elderly had significantly fewer copies of the butyryl-CoA:acetate CoA-transferase gene than young omnivores (P=0.014), while vegetarians showed the highest number of copies (P=0.048). The thermal denaturation of the butyryl-CoA:acetate CoA-transferase gene variant melting curve related to Roseburia/Eubacterium rectale spp. was significantly more variable in the vegetarians than in the elderly. The Clostridium cluster XIVa was more abundant in vegetarians (P=0.049) and in omnivores (P<0.01) than in the elderly group. Gastrointestinal microbiota of the elderly is characterized by decreased butyrate production capacity, reflecting increased risk of degenerative diseases. These results suggest that the butyryl-CoA:acetate CoA-transferase gene is a valuable marker for gastrointestinal microbiota function. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.",
"title": "Quantification of butyryl CoA:acetate CoA-transferase genes reveals different butyrate production capacity in individuals according to diet and age."
},
{
"docid": "MED-3582",
"text": "Breakfasts of lentils or wholemeal bread of identical carbohydrate content were taken by seven healthy volunteers. The lentils produced a significant 71% (p less than 0.001) reduction in the blood glucose area and flattened the plasma insulin and gastric inhibitory polypeptide responses by comparison with the bread. In addition, the lentil breakfast was followed by a significantly flatter blood glucose response to the standard bread lunch which followed 4 h later (by 38%, p less than 0.01). The blood glucose pattern was mimicked by feeding the bread breakfast slowly over the 4 h before lunch. Giving a bread breakfast containing a quarter of the carbohydrate reduced the breakfast glucose profile but resulted in a significantly impaired blood glucose response to lunch (168% of control, p less than 0.01). These results, together with breath hydrogen studies, performed on a separate group of four volunteers, indicate that the flattened response to lentils is not due to carbohydrate malabsorption. Slow release or \"lente\" carbohydrate foods such as lentils may form a useful part of the diets of those with impaired carbohydrate tolerance.",
"title": "Slow release dietary carbohydrate improves second meal tolerance."
},
{
"docid": "MED-3894",
"text": "The purpose of this study was to examine the effects of a natural carbohydrate (CHO) source in the form of sun-dried raisins (SDRs) vs. Sports Jelly Beans™ (SJBs) on endurance performance in trained cyclists and triathletes. Ten healthy men (18-33 years) completed 1 water-only acclimatization exercise trial and 2 randomized exercise trials administered in a crossover fashion. Each trial consisted of a 120-minute constant-intensity glycogen depletion period followed by a 10-km time trial (TT). During each experimental trial, participants consumed isocaloric amounts of SDRs or SJBs in 20-minute intervals. Measurements included time to complete 10-km TT, power output during 10-km TT, blood glucose levels and respiratory exchange ratio during glycogen depletion period, rate of perceived exertion (RPE), 'flow' questionnaire responses, and a hedonic (i.e., pleasantness) sensory acceptance test. There were no significant differences in endurance performance for TT time (SDRs vs. SJBs, 17.3 ± 0.4 vs. 17.3 ± 0.4 seconds) or power (229.3 ± 13.0 vs. 232.0 ± 13.6 W), resting blood glucose levels (5.8 ± 04 mmol·L(-1) for SDRs and 5.4 ± 0.2 mmol·L(-1) for SJBs), RPE, or flow experiences between SDR and SJB trials. However, the mean sensory acceptance scores were significantly higher for the SDRs compared to the SJBs (50.7 ± 1.7 vs. 44.3 ± 2.7). Consuming SDRs or SJBs during 120 minutes of intense cycling results in similar subsequent TT performances and are equally effective in maintaining blood glucose levels during exercise. Therefore, SDRs are a natural, pleasant, cost-effective CHO alternative to commercial SJBs that can be used during moderate- to high-intensity endurance exercise.",
"title": "Sun-dried raisins are a cost-effective alternative to Sports Jelly Beans in prolonged cycling."
},
{
"docid": "MED-719",
"text": "In addition to causing embarrassment and unease, flatulence is linked to a variety of symptoms, some of which may be distressing. This review describes the origins of intestinal gas, its composition and methods which have been developed for its analysis. Emphasis is placed upon the effects of legumes in the diet in producing excessive intestinal gas and, particularly, on the role of raffinose-type oligosaccharides, containing alpha-galactosidic groupings. Suggestions for overcoming the problem are presented, including drug treatment, enzyme treatment, food processing and plant breeding. It is emphasised that removal of all raffinose-oligosaccharides from beans does not remove the problem of flatulence in animals and man; the compounds responsible--though assumed to be polysaccharides (or polysaccharide-derived oligomers formed by processing or cooking)--have yet to be characterised.",
"title": "Flatulence--causes, relation to diet and remedies."
},
{
"docid": "MED-3581",
"text": "BACKGROUND: Low postprandial blood glucose is associated with low risk of metabolic diseases. A meal's ability to diminish the glucose response to carbohydrates eaten during the following meal is known as the \"second-meal effect\" (SME). The reduced glycemia elicited by low-glycemic-index (LGI) foods consumed during the first meal has been suggested as the main mechanism for SME. However, LGI foods often increase colonic fermentation because of the presence of fiber and resistant starch. OBJECTIVE: The objective was to study the SME of greater fermentation of high-glycemic-index (HGI) and LGI carbohydrates eaten during a previous meal. DESIGN: Ten healthy volunteers ate 3 breakfast test meals consisting of sponge cakes made with rapidly digestible, nonfermentable amylopectin starch plus cellulose (HGI meal), amylopectin starch plus the fermentable disaccharide lactulose (HGI-Lac meal), or slowly digestible, partly fermentable amylose starch plus cellulose (LGI meal). Five hours later, subjects were fed the same standard lunch containing 93 g available carbohydrates. Blood was collected for measurement of glucose, insulin, and nonesterified fatty acids (NEFAs). Breath hydrogen was measured as a marker of colonic fermentation. Postlunch gastric emptying was measured by using ultrasonography. RESULTS: Both the HGI-Lac and LGI meals improved glucose tolerance at lunch. In the case of the HGI-Lac meal, this effect was concomitant with low NEFA concentrations and delayed gastric emptying. CONCLUSION: Fermentable carbohydrates, independent of their effect on a food's glycemic index, have the potential to regulate postprandial responses to a second meal by reducing NEFA competition for glucose disposal and, to a minor extent, by affecting intestinal motility.",
"title": "Colonic fermentation of indigestible carbohydrates contributes to the second-meal effect."
},
{
"docid": "MED-4510",
"text": "Background and Aims Studies evaluating the effect of legume consumption on cholesterol have focused on soybeans, however non-soy legumes, such as a variety of beans, peas, and some seeds, are commonly consumed in Western countries. We conducted a meta-analysis of randomized controlled trials evaluating the effects of non-soy legume consumption on blood lipids. Methods and Results Studies were retrieved by searching MEDLINE (from January 1966 through July 2009), EMBASE (from January 1980 to July 2009), and the Cochrane Collaboration's Central Register of Controlled Clinical Trials using the following terms as medical subject headings and keywords: fabaceae not soybeans not isoflavones and diet or dietary fiber and cholesterol or hypercholesterolemia or triglycerides or cardiovascular diseases. Bibliographies of all retrieved articles were also searched. From 140 relevant reports, 10 randomized clinical trials were selected which compared a non-soy legume diet to control, had a minimum duration of 3 weeks, and reported blood lipid changes during intervention and control. Data on sample size, participant characteristics, study design, intervention methods, duration, and treatment results were independently abstracted by 2 investigators using a standardized protocol. Data from 10 trials representing 268 participants were examined using a random-effects model. Pooled mean net change in total cholesterol for those treated with a legume diet compared to control was −11.8 mg/dL (95% confidence interval [CI], −16.1 to −7.5); mean net change in low density lipoprotein cholesterol was −8.0 mg/dL (95% CI, −11.4 to −4.6). Conclusion These results indicate that a diet rich in legumes other than soy decreases total and LDL cholesterol.",
"title": "Non-Soy Legume Consumption Lowers Cholesterol Levels: A Meta-Analysis of Randomized Controlled Trials"
},
{
"docid": "MED-4680",
"text": "OBJECTIVE: To investigate associations between dietary intakes throughout childhood and age at menarche, a possible indicator of future risk of disease, in a contemporary cohort of British girls. DESIGN: Diet was assessed by FFQ at 3 and 7 years of age, and by a 3 d unweighed food diary at 10 years. Age at menarche was categorised as before or after 12 years 8 months, a point close to the median age in this cohort. SETTING: Bristol, South-West England. SUBJECTS: Girls (n 3298) participating in the Avon Longitudinal Study of Parents and Children. RESULTS: Higher energy intakes at 10 years were positively associated with the early occurrence of menarche, but this association was removed on adjusting for body size. Total and animal protein intakes at 3 and 7 years were positively associated with age at menarche ≤12 years 8 months (adjusted OR for a 1 sd increase in protein at 7 years: 1·14 (95 % CI 1·04, 1·26)). Higher PUFA intakes at 3 and 7 years were also positively associated with early occurrence of menarche. Meat intake at 3 and 7 years was strongly positively associated with reaching menarche by 12 years 8 months (OR for menarche in the highest v. lowest category of meat consumption at 7 years: 1·75 (95 % CI 1·25, 2·44)). CONCLUSIONS: These data suggest that higher intakes of protein and meat in early to mid-childhood may lead to earlier menarche. This may have implications for the lifetime risk of breast cancer and osteoporosis.",
"title": "Diet throughout childhood and age at menarche in a contemporary cohort of British girls."
},
{
"docid": "MED-4149",
"text": "Oxidative stress, i.e. excessive content of reactionary, oxygen, and nitrogen compounds (ROAC), including free radicals, is one of the causes of various dangerous diseases as well as premature aging. The adverse effect of free radicals can be neutralized by antioxidants. In order to carry out antioxidant therapy, one needs to know the contents of antioxidants in food products. We have created the databank for the contents of antioxidants in 1,140 food products, beverages, etc. Apart from water-soluble antioxidants, fat-soluble antioxidants in dairy and fish products, cacao, chocolate, nuts etc. were determined for the first time using an amperometric method.",
"title": "Creation of a databank for content of antioxidants in food products by an amperometric method."
}
] |
[
{
"docid": "MED-2140",
"text": "Background Around the world, beans and rice are commonly consumed together as a meal. With type 2 diabetes increasing, the effect of this traditional diet pattern on glycemic response has not been studied fully. Methods We evaluated the glycemic response of bean and rice traditional meals compared to rice alone in adults with type 2 diabetes. Seventeen men and women with type 2 diabetes controlled by metformin (n = 14) or diet/exercise (n = 3) aged 35–70 years participated in the randomized 4 × 4 crossover trial. The white long grain rice control, pinto beans/rice, black beans/rice, red kidney beans/rice test meals, matched for 50 grams of available carbohydrate, were consumed at breakfast after a 12 hour fast. Capillary blood glucose concentrations at baseline and at 30 minute intervals up to 180 minutes postprandial were collected. MANOVA for repeated measures established glucose differences between treatments. Paired t tests identified differences between bean types and the rice control following a significant MANOVA. Results Postprandial net glucose values were significantly lower for the three bean/rice treatments in contrast to the rice control at 90, 120 and 150 minutes. Incremental area under the curve values were significantly lower for the pinto and black bean/rice meals compared to rice alone, but not for kidney beans. Conclusions Pinto, dark red kidney and black beans with rice attenuate the glycemic response compared to rice alone. Promotion of traditional foods may provide non-pharmaceutical management of type 2 diabetes and improve dietary adherence with cultural groups. Trial registration Clinical Trials number NCT01241253",
"title": "Bean and rice meals reduce postprandial glycemic response in adults with type 2 diabetes: a cross-over study"
},
{
"docid": "MED-1612",
"text": "Type II diabetic subjects were given 50 g protein, 50 g glucose, or 50 g glucose with 50 g protein as a single meal in random sequence. The plasma glucose and insulin response was determined over the subsequent 5 h. The plasma glucose area above the baseline following a glucose meal was reduced 34% when protein was given with the glucose. When protein was given alone, the glucose concentration remained stable for 2 h and then declined. The insulin area following glucose was only modestly greater than with a protein meal (97 +/- 35, 83 +/- 19 microU X h/ml, respectively). When glucose was given with protein, the mean insulin area was considerably greater than when glucose or protein was given alone (247 +/- 33 microU X h/ml). When various amounts of protein were given with 50 g glucose, the insulin area response was essentially first order. Subsequently, subjects were given 50 g glucose or 50 g glucose with 50 g protein as two meals 4 h apart in random sequence. The insulin areas were not significantly different for each meal but were higher when protein + glucose was given. After the second glucose meal the plasma glucose area was 33% less than after the first meal. Following the second glucose + protein meal the plasma glucose area was markedly reduced, being only 7% as large as after the first meal. These data indicate that protein given with glucose will increase insulin secretion and reduce the plasma glucose rise in at least some type II diabetic persons.",
"title": "Effect of protein ingestion on the glucose and insulin response to a standardized oral glucose load."
},
{
"docid": "MED-3136",
"text": "The objective of this study was to determine the influence of frequent and long-term consumption of legume seeds on colonic function. Two groups of subjects were studied--one group habitually consumed legume seeds as part of their normal diet, a second group only infrequently consumed legumes. No differences between these groups could be detected for fecal output and frequency, intestinal transit time, VFA excretion or fecal pH during 23-day study periods in which subjects consumed either their usual diet or 100 g red kidney beans, daily. However, the addition of beans to the diets of both groups provided significantly more dietary fiber, and produced greater fecal output and a higher concentration of VFA in feces. Fecal output appeared to be determined by two independent parameters--dietary fiber intake and VFA excretion. Beans provided a physiologically useful source of dietary fiber and favorably influenced colonic function.",
"title": "Influence of frequent and long-term bean consumption on colonic function and fermentation."
},
{
"docid": "MED-2970",
"text": "There is increasing evidence that the postprandial state is an important contributing factor to chronic disease. The role of fruit phenolic compounds to protect health and lower disease risk through their actions in mitigating fed-state metabolic and oxidative stressors is of interest and the topic of the present paper. Two main questions are posed: first, what is the role of plant foods, specifically fruits rich in complex and simple phenolic compounds in postprandial metabolic management; and second, does the evidence support consuming these fruits with meals as a practical strategy to preserve health and lower risk for disease? This review provides an overview of the postprandial literature, specifically on the effect of fruits and their inherent phenolic compounds in human subjects on postprandial lipaemia, glycaemia/insulinaemia and associated events, such as oxidative stress and inflammation. Among the identified well-controlled human trials using a postprandial paradigm, >50 % of the trials used wine or wine components and the remaining used various berries. Notwithstanding the need for more research, the collected data suggest that consuming phenolic-rich fruits increases the antioxidant capacity of the blood, and when they are consumed with high fat and carbohydrate 'pro-oxidant and pro-inflammatory' meals, they may counterbalance their negative effects. Given the content and availability of fat and carbohydrate in the Western diet, regular consumption of phenolic-rich foods, particularly in conjunction with meals, appears to be a prudent strategy to maintain oxidative balance and health.",
"title": "Postprandial metabolic events and fruit-derived phenolics: a review of the science."
},
{
"docid": "MED-5260",
"text": "OBJECTIVES: The goal of this study was to evaluate the effects of the phenolic content of virgin olive oil on endothelial reactivity. BACKGROUND: Endothelial-dependent vasodilatation is impaired during the postprandial state, and oxidative stress could play a key role in its development. METHODS: Twenty-one hypercholesterolemic volunteers received two breakfasts, using a randomized sequential crossover design. Both arms received the same olive oil, but one had its phenolic acid content reduced from 400 to 80 ppm. Ischemic reactive hyperemia (IRH) was measured with a laser-Doppler procedure at baseline and 2 h and 4 h after oil intake. Postprandial plasma concentrations of lipid fractions, lipoperoxides (LPO), 8-epi prostaglandin-F(2alpha), and nitrates/nitrites (NO(x)) were obtained at baseline and after 2 h of the fat meal. RESULTS: The intake of the polyphenol-rich breakfast was associated with an improvement in endothelial function, as well as a greater increase in concentrations of NO(x) (p < 0.001) and a lower increase in LPO (p < 0.005) and 8-epi prostaglandin-F2alpha (p < 0.001) than the ones induced by the low polyphenol fat meal. A positive correlation was found to exist between NO(x) and enhanced endothelial function at the second hour (r = 0.669; p < 0.01). Furthermore, a negative correlation was found between IRH and LPO (r = -0.203; p < 0.05) and 8-epi prostaglandin-F2alpha levels (r = -0.440; p < 0.05). CONCLUSIONS: A meal containing high-phenolic virgin olive oil improves ischemic reactive hyperemia during the postprandial state. This phenomenon might be mediated via reduction in oxidative stress and the increase of nitric oxide metabolites.",
"title": "Phenolic content of virgin olive oil improves ischemic reactive hyperemia in hypercholesterolemic patients."
},
{
"docid": "MED-1671",
"text": "BACKGROUND: Sucrose induces high postprandial glucose and insulin responses. In vitro studies suggest that berries may reduce the digestion and absorption of sucrose and thereby suppress postprandial glycemia, but the evidence in humans is limited. OBJECTIVE: We investigated the effects of sucrose ingested with blackcurrants (Ribes nigrum) and lingonberries (Vaccinium vitis-idaea) on postprandial glucose, insulin, and free fatty acid responses. DESIGN: Twenty healthy women participated in a randomized, controlled, crossover meal study. They consumed whole blackcurrants or lingonberries (150 g served as purées) or blackcurrant or lingonberry nectars (300 mL), each with 35 g added sucrose. Sucrose alone (35 g in 300 mL water) was used as a reference. Blood samples were collected at 0, 15, 30, 45, 60, 90, and 120 min. RESULTS: In comparison with sucrose alone, ingestion of sucrose with whole berries resulted in reduced glucose and insulin concentrations during the first 30 min and a slower decline during the second hour and a significantly improved glycemic profile. Berries prevented the sucrose-induced late postprandial hypoglycemic response and the compensatory free fatty acid rebound. Nearly similar effects were observed when sucrose was consumed with berry nectars. The improved responses were evident despite the higher content of available carbohydrate in the berry and nectar meals, because of the natural sugars present in berries. CONCLUSIONS: Blackcurrants and lingonberries, as either whole berries or nectars, optimize the postprandial metabolic responses to sucrose. The responses are consistent with delayed digestion of sucrose and consequent slower absorption of glucose.",
"title": "Postprandial glucose, insulin, and free fatty acid responses to sucrose consumed with blackcurrants and lingonberries in healthy women."
},
{
"docid": "MED-1880",
"text": "Legumes are the basés diet in several countries. They hold a high nutritional value, but other properties related to human health are nowadays being studied. The aim of this work was to study the influence of processes (boiling or germination) on the phenolic composition of dark beans (Phaseolus vulgaris L. c.v. Tolosana) and their effect on their antioxidant, neuroprotective and anticancer ability. Phenolic composition of raw and processed dark beans was analysed by HPLC-PAD and HPLC-ESI/MS. The antioxidant activity was evaluated by ORAC. Astrocytes cultures (U-373) have been used to test their neuroprotective effect. Anticancer activities were evaluated on three different cell lines (renal adenocarcinoma (TK-10), breast adenocarcinoma (MCF-7) and melanoma (UACC-62)) by sulphorhodamine B method. Qualitative and quantitative differences in phenolic composition have been observed between raw and processed dark beans that influence the antioxidant activity, mainly for germinated samples which show a decrease of antioxidant capacity. Although every assayed extracts decreased reactive oxygen species release and exhibited cytotoxicity activities on cancer cell lines, raw beans proved to be the most active in neuroprotective and antitumoral effects; this sample is especially rich in phenolic compounds, mainly anthocyanins. This study further demonstrated that phenolic composition of dark beans is related with cooking process and so with their neuroprotective and anticancer activity; cooking of dark beans improves their digestion and absorption at intestinal level, while maintaining its protective ability on oxidative process at cellular level. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Effect of cooking and germination on phenolic composition and biological properties of dark beans (Phaseolus vulgaris L.)."
},
{
"docid": "MED-5079",
"text": "OBJECTIVE: To determine effects of daily intake of 1/2 cup pinto beans, black-eyed peas or carrots (placebo) on risk factors for coronary heart disease (CHD) and diabetes mellitus (DM) in free-living, mildly insulin resistant adults over an 8 week period. METHODS: Randomized, crossover 3x3 block design. Sixteen participants (7 men, 9 women) received each treatment for eight-weeks with two-week washouts. Fasting blood samples collected at beginning and end of periods were analyzed for total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol, triacylglycerols, high-sensitivity C-reactive protein, insulin, glucose, and hemoglobin A1c. RESULTS: A significant treatment-by-time effect impacted serum TC (p = 0.026) and LDL (p = 0.033) after eight weeks. Paired t-tests indicated that pinto beans were responsible for this effect (p = 0.003; p = 0.008). Mean change of serum TC for pinto bean, black-eyed pea and placebo were -19 +/- 5, 2.5 +/- 6, and 1 +/- 5 mg/dL, respectively (p = 0.011). Mean change of serum LDL-C for pinto bean, black-eyed pea and placebo were -14 +/- 4, 4 +/- 5, and 1 +/- 4 mg/dL, in that order (p = 0.013). Pinto beans differed significantly from placebo (p = 0.021). No significant differences were seen with other blood concentrations across the 3 treatment periods. CONCLUSIONS: Pinto bean intake should be encouraged to lower serum TC and LDL-C, thereby reducing risk for CHD.",
"title": "Pinto bean consumption reduces biomarkers for heart disease risk."
},
{
"docid": "MED-3138",
"text": "Background Many consumers avoid eating beans because they believe legume consumption will cause excessive intestinal gas or flatulence. An increasing body of research and the 2010 Dietary Guidelines for Americans supports the benefits of a plant-based diet, and legumes specifically, in the reduction of chronic disease risks. The purpose of the current research was to investigate the perception of increased flatulence and gastrointestinal discomfort among participants who consumed a ½ cup of beans daily for 8 or 12 weeks. Methods Participants in three studies to test the effects of beans on heart disease biomarkers completed the same weekly questionnaire to assess gastrointestinal discomfort issues such as increased flatulence, stool changes, and bloating. Studies 1 and 2 were randomized crossover trials. Participants consumed ½ cup of pinto beans, black-eyed peas, and canned carrots as control (n = 17) in Study 1 for three randomized 8-week phases. For Study 2, participants ate ½ cup baked beans or canned carrots as control (n = 29) for two randomized 8-week phases. Study 3 was a parallel arm trial with 40 subjects receiving ½ cup pinto beans and 40 consuming a control soup for 12 weeks. Changes in the frequency of perceived flatulence, stool characteristics, and bloating were the primary outcome measures. Chi-square distributions were examined for the presence or absence of symptoms and demographic characteristics to determine differences by gender, age, body mass index (BMI), and bean type. Results Less than 50% reported increased flatulence from eating pinto or baked beans during the first week of each trial, but only 19% had a flatulence increase with black-eyed peas. A small percentage (3-11%) reported increased flatulence across the three studies even on control diets without flatulence-producing components. Conclusions People's concerns about excessive flatulence from eating beans may be exaggerated. Public health nutritionists should address the potential for gastrointestinal discomfort when increasing fiber intake from beans with clients. It is important to recognize there is individual variation in response to different bean types.",
"title": "Perceptions of flatulence from bean consumption among adults in 3 feeding studies"
},
{
"docid": "MED-2570",
"text": "The functional properties, including antioxidant and chemopreventative capacities as well as the inhibitory effects on angiotensin-converting enzyme (ACE), α-glucosidase and pancreatic lipase, of three Australian-grown faba bean genotypes (Nura, Rossa and TF(Ic*As)*483/13) were investigated using an array of in vitro assays. Chromatograms of on-line post column derivatisation assay coupled with HPLC revealed the existence of active phenolics (hump) in the coloured genotypes, which was lacking in the white-coloured breeding line, TF(Ic*As)*483/13. Roasting reduced the phenolic content, and diminished antioxidant activity by 10-40 % as measured by the reagent-based assays (diphenylpicrylhydrazyl, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) and oxygen radical absorbance capacity) in all genotypes. Cell culture-based antioxidant activity assay (cellular antioxidant activity) showed an increase of activity in the coloured genotypes after roasting. Faba bean extracts demonstrated cellular protection ability against H₂O₂-induced DNA damage (assessed using RAW264.7 cells), and inhibited the proliferation of all human cancer cell lines (BL13, AGS, Hep G2 and HT-29) evaluated. However, the effect of faba bean extracts on the non-transformed human cells (CCD-18Co) was negligible. Flow cytometric analyses showed that faba bean extracts successfully induced apoptosis of HL-60 (acute promyelocytic leukaemia) cells. The faba bean extracts also exhibited ACE, α-glucosidase and pancreatic lipase inhibitory activities. Overall, extracts from Nura (buff-coloured) and Rossa (red-coloured) were comparable, while TF(Ic*As)*483/13 (white-coloured) contained the lowest phenolic content and exhibited the least antioxidant and enzyme inhibition activities. These results are important to promote the utilisation of faba beans in human diets for various health benefits.",
"title": "In vitro investigations of the potential health benefits of Australian-grown faba beans (Vicia faba L.): chemopreventative capacity and inhibitory ..."
},
{
"docid": "MED-3141",
"text": "OBJECTIVE: To evaluate the associations with chronic disease risk and mortality of the consequences of bean-free diets in Taiwanese adults with regard to gender. DESIGN: A sub-sample of the National Health Interview Survey (NHIS) in 2001 agreed to physical examination in the subsequent year. This group then took part in the Taiwanese Survey of Hyperglycaemia, Hyperlipidaemia and Hypertension (TwSHHH) in 2002. SETTING: Individual records were linked to the eventual death files from 2002 to 2008. SUBJECTS: Up to the end of 2008, a total of 2820 men and 2950 women were tracked by death registry over the 6·8 years of follow-up. RESULTS: Among 38,077 person-years, an average follow-up 6·5 years, 225 all-cause deaths were identified. Generalized linear models showed beans to be favourable for metabolic syndrome (other than for fasting glucose) in men; in women, beans were favourable for waist circumference and HbA1c. Cumulative logistic regression models for the effect of a bean-free diet on metabolic syndrome scores according to the Taiwanese-modified National Cholesterol Education Program-Adult Treatment Panel III (NCEP-tw) gave adjusted odds ratios of 1·83 in men and 1·45 in women. Cox regression models for the bean-free diet showed an increased hazard ratio for all-cause mortality among women (1·98, 95% CI 1·03, 3·81) but not men (1·28, 95% CI 0·76, 2·16). CONCLUSIONS: A bean-free diet may play a role in developing the metabolic syndrome in both genders, and is a significant predictor of all-cause mortality in Taiwanese women but not men.",
"title": "A bean-free diet increases the risk of all-cause mortality among Taiwanese women: the role of the metabolic syndrome."
},
{
"docid": "MED-2144",
"text": "Bean pods (Phaseolus vulgaris) are among the most widely used traditional remedies against diabetes mellitus. Historical knowledge is summarized and compared to recent study results. Reports dating from the first half of the 20(th) century as well as recent publications show contradictory results. It seems that Phaseolus preparations should not be considered the first choice in phytopharmaceutical treatment of diabetes or lead structure research. To be effective, fairly high doses of aqueous extracts need to be given. Because of their fiber content and an alpha-amylase inhibitory effect, beans might be more useful as food components in preventing or ameliorating type 2 diabetes.",
"title": "Beans and diabetes: Phaseolus vulgaris preparations as antihyperglycemic agents."
},
{
"docid": "MED-4991",
"text": "BACKGROUND: Epidemiological studies have shown positive findings associated with legume consumption and measures of cardiovascular disease and obesity. However, few observational trials have examined beans as a separate food variable when determining associations with health parameters. OBJECTIVE: To determine the association of consuming beans on nutrient intakes and physiological parameters using the National Health and Examination Survey (NHANES) 1999-2002. METHODS: Using data from NHANES 1999-2002, a secondary analysis was completed with a reliable 24-hour dietary recall where three groups of bean consumers were identified (N = 1,475). We determined mean nutrient intakes and physiological values between bean consumers and non-consumers. Least square means, standard errors and ANOVA were calculated using appropriate sample weights following adjustment for age, gender, ethnicity and energy. RESULTS: Relative to non-consumers, bean consumers had higher intakes of dietary fiber, potassium, magnesium, iron, and copper (p's < 0.05). Those consuming beans had a lower body weight (p = 0.008) and a smaller waist size (p = 0.043) relative to non-consumers. Additionally, consumers of beans had a 23% reduced risk of increased waist size (p = 0.018) and a 22% reduced risk of being obese (p = 0.026). Also, baked bean consumption was associated with a lower systolic blood pressure. CONCLUSIONS: Bean consumers had better overall nutrient intake levels, better body weights and waist circumferences, and lower systolic blood pressure in comparison to non-consumers. These data support the benefits of bean consumption on improving nutrient intake and health parameters.",
"title": "Bean consumption is associated with greater nutrient intake, reduced systolic blood pressure, lower body weight, and a smaller waist circumference ..."
},
{
"docid": "MED-5078",
"text": "In this study, solid fermentation of steamed black soybean with various GRAS (Generally recognized as safe) filamentious-fungi including Aspergillus awamori, Aspergillus oryzae BCRC 30222, Aspergillus sojae BCRC 30103, Rhizopus azygosporus BCRC 31158 and Rhizopus sp. No. 2 was performed. Mutagenicity and antimutagenicity of the methanol extracts of unfermented and fermented steamed black soybeans against 4-nitroquinoline-N-oxide (4-NQO), a direct mutagen and Benzo[a]pyrene (B[a]P), an indirect mutagen, on Salmonella Typhimurium TA100 and TA 98, were examined. The methanol extracts of unfermented and fermented steamed black soybeans show no mutagenic activity for either test strains at the doses tested. The extracts inhibited mutagenesis by either 4-NQO or B[a]P in S. Typhimurium TA100 and TA98. Fermentation with fungi also enhanced the antimutagenic effect of black soybean while the antimutagenic effect of the fermented black soybeans extract varied with the starter organism, mutagen, and test strain of S. Typhimurium examined. Generally, the extracts of A. awamori-fermented black soybean exhibited the highest antimutagenic effect. With strain TA100, the inhibitory effects of 5.0 mg of A. awamori-fermented black soybean extract per plate on the mutagenic effects of 4-NQO and B[a]P were 92% and 89%, respectively, while the corresponding rates for extract of unfermented were 41% and 63%, respectively. With strain 98, the inhibition rates were 94 and 81% for the fermented bean extract and 58% and 44% for the unfermented bean extracts. Testing of extracts prepared from black soybean by A. awamori at temperatures 25, 30 and 35 degrees C and for times of 1-5 days revealed that, generally, the extract prepared from beans fermented at 30 degrees C for 3 days exhibited the greatest inhibition against the mutagenic effects of 4-NQO and B[a]P.",
"title": "Mutagenic and antimutagenic effects of methanol extracts of unfermented and fermented black soybeans."
},
{
"docid": "MED-4989",
"text": "BACKGROUND: A high nutrient density (HND) vegetable-based diet offers a dietary model extremely low in saturated fat as well as refined carbohydrates and emphasizes a liberal intake of fresh fruits, vegetables, beans, and nuts. We conducted a retrospective chart review of patients who came to a family practice office seeking nutritional counseling for weight loss. All of these patients were prescribed an HND diet in an extended counseling session with a family physician. METHODS: A convenience sample (N = 56) of all patients seeking dietary counseling for weight loss from a family practice physician in a 3-year period was included in the chart review. No personal identifying data were recorded. The initial counseling sessions averaged 1 hour in length. Patients were provided with a sample HND daily meal plan and recipes and with verbal and written information about the rationale for the diet. Data recorded from patients' charts at 6-month intervals for up to 2 years of follow-up (when available) included weight, blood pressure, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and cholesterol:HDL ratio. Non-parametric statistical testing using the Friedman rank order (exact) test for k-related samples was conducted. A follow-up survey on adherence and medication use was completed by 38 patients. RESULTS: Of the 33 patients who returned for follow-up after 1 year, the mean weight loss was 31 lbs (P = .000). Of the 19 patients who returned after 2 years, the mean weight loss was 53 lbs (P = .000), mean cholesterol fell by 13 points, LDL by 15 points, triglycerides by 17 points, and cardiac risk ratio dropped from 4.5 to 3.8. Changes in systolic and diastolic blood pressure were highly significant at all follow-up time intervals (P < or = .001). There was a significant correlation between adherence and degree of weight loss (P = .011). CONCLUSIONS: Weight loss was sustained in patients who returned for follow-up and was more substantial in those who reported good adherence to the recommendations. However, many patients were lost to follow-up. Favorable changes in lipid profile and blood pressure were noted. An HND diet has the potential to provide sustainable, significant, long-term weight loss and may provide substantial lowering of cardiac risk in patients who are motivated and provided with extended one-on-one counseling and follow-up visits. Development of tools to aid in patient retention is an area for possible further study. Clinical trials with long-term follow-up are needed to further test the therapeutic potential and to examine adherence and follow-up issues related to this dietary approach. An HND diet as demonstrated with this group may be the most health-favorable and effective way to lose weight for appropriately motivated patients.",
"title": "Effect of a high nutrient density diet on long-term weight loss: a retrospective chart review."
},
{
"docid": "MED-2010",
"text": "Legumes (including alfalfa, clover, lupins, green beans and peas, peanuts, soybeans, dry beans, broad beans, dry peas, chickpeas, and lentils) represent an important component of the human diet in several areas of the world, especially in the developing countries, where they complement the lack of proteins from cereals, roots, and tubers. In some regions of the world, legume seeds are the only protein supply in the diet. The health benefits of legume consumption have received rising interest from researchers, and their consumption and production extends worldwide. Among European countries, higher legume consumption is observed around the Mediterranean, with per capita daily consumption between 8 and 23 g, while in Northern Europe, the daily consumption is less than 5 g per capita. The physiological effects of different legumes vary significantly. These differences may result from the polysaccharides composition, in particular, the quantity and variety of dietary fibers and starch, protein make-up, and variability in phytochemical content. The majority of legumes contain phytochemicals: bioactive compounds, including enzyme inhibitors, phytohemagglutinins (lectins), phytoestrogens, oligosaccharides, saponins, and phenolic compounds, which play metabolic roles in humans who frequently consume these foods. Dietary intake of phytochemicals may provide health benefits, protecting against numerous diseases or disorders, such as coronary heart disease, diabetes, high blood pressure and inflammation. The synergistic or antagonistic effects of these phytochemical mixtures from food legumes, their interaction with other components of the diet, and the mechanism of their action have remained a challenge with regard to understanding the role of phytochemicals in health and diseases. Their mitigating effects and the mechanism of their action need to be further addressed if we are to understand the role of phytochemicals in health and diseases. This review provides an overview of the nutritional quality of legumes and their potential contribution in cardiometabolic risk prevention.",
"title": "Nutritional quality of legumes, and their role in cardiometabolic risk prevention: a review."
},
{
"docid": "MED-4559",
"text": "The cardiovascular risk reduction associated with different statins for the prevention of cardiovascular disease and the cardiovascular risk increase associated with excess dietary intake of fat have been quantified. However, these relative risks have never been directly juxtaposed to determine whether an increase in relative risk by 1 activity could be neutralized by an opposing change in relative risk from a second activity. The investigators compared the increase in relative risk for cardiovascular disease associated with the total fat and trans fat content of fast foods against the relative risk decrease provided by daily statin consumption from a meta-analysis of statins in primary prevention of coronary artery disease (7 randomized controlled trials including 42,848 patients). The risk reduction associated with the daily consumption of most statins, with the exception of pravastatin, is more powerful than the risk increase caused by the daily extra fat intake associated with a 7-oz hamburger (Quarter Pounder) with cheese and a small milkshake. In conclusion, statin therapy can neutralize the cardiovascular risk caused by harmful diet choices. In other spheres of human activity, individuals choosing risky pursuits (motorcycling, smoking, driving) are advised or compelled to use measures to minimize the risk (safety equipment, filters, seatbelts). Likewise, some individuals eat unhealthily. Routine accessibility of statins in establishments providing unhealthy food might be a rational modern means to offset the cardiovascular risk. Fast food outlets already offer free condiments to supplement meals. A free statin-containing accompaniment would offer cardiovascular benefits, opposite to the effects of equally available salt, sugar, and high-fat condiments. Although no substitute for systematic lifestyle improvements, including healthy diet, regular exercise, weight loss, and smoking cessation, complimentary statin packets would add, at little cost, 1 positive choice to a panoply of negative ones.",
"title": "Can a statin neutralize the cardiovascular risk of unhealthy dietary choices?"
},
{
"docid": "MED-5265",
"text": "BACKGROUND: Persons following current dietary guidelines have a lower risk of mortality from coronary heart disease. OBJECTIVE: The objective was to compare the short-term effect of a high-fat meal and a high-carbohydrate meal, with and without dietary antioxidants, on vasomotor, antiplatelet, and hemostatic functions of the endothelium in healthy subjects. DESIGN: In an observer-blinded, randomized crossover study, 25 (13 men and 12 women) healthy subjects were given each of 3 meals in random order at 1-wk intervals: a high-fat meal (760 kcal), an isoenergetic high-carbohydrate meal, and a high-fat meal with dietary antioxidants from vegetables (865 kcal). Endothelial functions, as assessed by hemodynamic and rheologic responses to L-arginine--the natural precursor of nitric oxide--were evaluated before and 4 h after each meal. RESULTS: Unlike the high-carbohydrate meal, the high-fat meal increased the plasma concentrations of triacylglycerol (P < 0.01); both meals activated hemostasis. The high-carbohydrate meal did not modify blood pressure, and platelet aggregation decreased in response to the L-arginine load (-7.1 +/- 2.3 mm Hg and -8.5 +/- 4.5%, respectively). After the high-fat meal, the decrease in blood pressure in response to L-arginine was reduced (-1 +/- 0.8 mm Hg), and platelet aggregation showed a paradoxical increase (4.1 +/- 2.1%; P < 0.01 compared with the high-carbohydrate meal). The high-fat meal with antioxidants partially restored the vascular response to L-arginine. CONCLUSION: Compared with a high-carbohydrate meal, a high-fat meal can modify endothelial functions toward a more atherogenetic profile, which is partially prevented by dietary antioxidants.",
"title": "Effect of dietary antioxidants on postprandial endothelial dysfunction induced by a high-fat meal in healthy subjects."
},
{
"docid": "MED-5153",
"text": "OBJECTIVES: We sought to investigate whether the addition of walnuts or olive oil to a fatty meal have differential effects on postprandial vasoactivity, lipoproteins, markers of oxidation and endothelial activation, and plasma asymmetric dimethylarginine (ADMA). BACKGROUND: Compared with a Mediterranean diet, a walnut diet has been shown to improve endothelial function in hypercholesterolemic patients. We hypothesized that walnuts would reverse postprandial endothelial dysfunction associated with consumption of a fatty meal. METHODS: We randomized in a crossover design 12 healthy subjects and 12 patients with hypercholesterolemia to 2 high-fat meal sequences to which 25 g olive oil or 40 g walnuts had been added. Both test meals contained 80 g fat and 35% saturated fatty acids, and consumption of each meal was separated by 1 week. Venipunctures and ultrasound measurements of brachial artery endothelial function were performed after fasting and 4 h after test meals. RESULTS: In both study groups, flow-mediated dilation (FMD) was worse after the olive oil meal than after the walnut meal (p = 0.006, time-period interaction). Fasting, but not postprandial, triglyceride concentrations correlated inversely with FMD (r = -0.324; p = 0.024). Flow-independent dilation and plasma ADMA concentrations were unchanged, and the concentration of oxidized low-density lipoproteins decreased (p = 0.051) after either meal. The plasma concentrations of soluble inflammatory cytokines and adhesion molecules decreased (p < 0.01) independently of meal type, except for E-selectin, which decreased more (p = 0.033) after the walnut meal. CONCLUSIONS: Adding walnuts to a high-fat meal acutely improves FMD independently of changes in oxidation, inflammation, or ADMA. Both walnuts and olive oil preserve the protective phenotype of endothelial cells.",
"title": "Acute effects of high-fat meals enriched with walnuts or olive oil on postprandial endothelial function."
},
{
"docid": "MED-5075",
"text": "The isothiocyanate, sulforaphane, has been implicated in the cancer-protective effects of brassica vegetables. When broccoli is consumed, sulforaphane is released from hydrolysis of glucoraphanin by plant myrosinase and/or colonic microbiota. The influence of meal composition and broccoli-cooking duration on isothiocyanate uptake was investigated in a designed experiment. Volunteers (n 12) were each offered a meal, with or without beef, together with 150 g lightly cooked broccoli (microwaved 2.0 min) or fully cooked broccoli (microwaved 5.5 min), or a broccoli seed extract. They received 3 g mustard containing pre-formed allyl isothiocyanate (AITC) with each meal. Urinary output of allyl (AMA) and sulforaphane (SFMA) mercapturic acids, the biomarkers of production of AITC and sulforaphane respectively, were measured for 24 h after meal consumption. The estimated yield of sulforaphane in vivo was about 3-fold higher after consumption of lightly cooked broccoli than fully cooked broccoli. Absorption of AITC from mustard was about 1.3-fold higher following consumption of the meat-containing meal compared with the non meat-containing alternative. The meal matrix did not significantly influence the hydrolysis of glucoraphanin and its excretion as SFMA from broccoli. Isothiocyanates may interact with the meal matrix to a greater extent if they are ingested pre-formed rather than after their production from hydrolysis of glucosinolates in vivo. The main influence on the production of isothiocyanates in vivo is the way in which brassica vegetables are cooked, rather than the effect of the meal matrix.",
"title": "Effect of meal composition and cooking duration on the fate of sulforaphane following consumption of broccoli by healthy human subjects."
},
{
"docid": "MED-5261",
"text": "OBJECTIVE—To examine the acute effects of consumption of monounsaturated (MUFAs) and saturated fatty acids (SAFAs) on endothelial function in subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS—A total of 33 participants were examined after consumption of two different isocaloric meals: one rich in MUFA and one rich in SAFA, in the form of extra-virgin olive oil and butter, respectively. Endothelial function was assessed by determination of flow-mediated dilatation (FMD). RESULTS—FMD did not change significantly after the MUFA-rich meal but declined after the SAFA-rich meal. The FMD during the experiment, expressed as incremental area under the curve, increased after the MUFA-rich meal by 5.2 ± 2.5% and decreased after the SAFA-rich meal by 16.7 ± 6.0% (Δ = −11.5 ± 6.4%; P = 0.008). CONCLUSIONS—Consumption of an SAFA-rich meal is harmful for the endothelium, while a MUFA-rich meal does not impair endothelial function in subjects with type 2 diabetes.",
"title": "Differential Effects of Two Isoenergetic Meals Rich in Saturated or Monounsaturated Fat on Endothelial Function in Subjects With Type 2 Diabetes"
},
{
"docid": "MED-2147",
"text": "Consumption of Phaseolus vulgaris bean species such as pinto, black, navy or kidney may be beneficial in the prevention and treatment of chronic diseases. In particular, conditions that are promoted by increased glycaemic stress (hyperglycaemia and hyperinsulinaemia) including diabetes, CVD and cancer seem to be reduced in individuals who eat more of these beans. The present paper discusses the influence of P. vulgaris species on glycaemic response and the impact that relationship may have on the risk of developing diabetes, CVD and cancer.",
"title": "Phaseolus beans: impact on glycaemic response and chronic disease risk in human subjects."
},
{
"docid": "MED-2580",
"text": "Adequate fruit and vegetable intake was suggested to protect against colorectal cancer and colorectal adenomas; however, several recent prospective studies reported no association. We examined the association between fruits and vegetables and adenomatous polyp recurrence in the Polyp Prevention Trial (PPT). The PPT was a low-fat, high-fiber, high-fruit, and vegetable dietary intervention trial of adenoma recurrence, in which there were no differences in the rate of adenoma recurrence in participants in the intervention and control arms of the trial. In this analysis of the entire PPT trial–based cohort, multiple logistic regression analysis was used to estimate the odds ratio (OR) of advanced and nonadvanced adenoma recurrence within quartiles of baseline and change (baseline minus the mean over 3 y) in fruit and vegetable intake, after adjustment for age, total energyy intake, use of nonsteroidal anti-inflammatory drugs, BMI, and gender. There were no significant associations between nonadvanced adenoma recurrence and overall change in fruit and vegetable consumption; however, those in the highest quartile of change in dry bean intake (greatest increase) compared with those in the lowest had a significantly reduced OR for advanced adenoma recurrence (OR = 0.35; 95% CI, 0.18–0.69; P for trend = 0.001). The median in the highest quartile of change in dry bean intake was 370% higher than the baseline intake. The PPT trial–based cohort provides evidence that dry beans may be inversely associated with advanced adenoma recurrence.",
"title": "High Dry Bean Intake and Reduced Risk of Advanced Colorectal Adenoma Recurrence among Participants in the Polyp Prevention Trial"
},
{
"docid": "MED-5118",
"text": "OBJECTIVE: To compare the effects of two commercially available soy milks (one made using whole soy beans, the other using soy protein isolate) with low-fat dairy milk on plasma lipid, insulin, and glucose responses. DESIGN: Randomized clinical trial, cross-over design. SUBJECTS: Participants were 30-65 years of age, n = 28, with pre-study LDL-cholesterol (LDL-C) concentrations of 160-220 mg/dL, not on lipid lowering medications, and with an overall Framingham risk score of <or=10%. INTERVENTION: Participants were required to consume sufficient milk to provide 25 g protein/d from each source. The protocol included three 4-week treatment phases, each separated from the next by a wash-out period of >or=4 weeks. RESULTS: Mean LDL-C concentration at the end of each phase (+/- SD) was 161 +/- 20, 161 +/- 26 and 170 +/- 24 mg/dL for the whole bean soy milk, the soy protein isolate milk, and the dairy milk, respectively (p = 0.9 between soy milks, p = 0.02 for each soy milk vs. dairy milk). No significant differences by type of milk were observed for HDL-cholesterol, triacylglycerols, insulin, or glucose. CONCLUSION: A 25 g dose of daily soy protein from soy milk led to a modest 5% lowering of LDL-C relative to dairy milk among adults with elevated LDL-C. The effect did not differ by type of soy milk and neither soy milk significantly affected other lipid variables, insulin or glucose.",
"title": "Effect of two types of soy milk and dairy milk on plasma lipids in hypercholesterolemic adults: a randomized trial."
},
{
"docid": "MED-5013",
"text": "INTRODUCTION: Endothelial dysfunction is known to occur in patients with coronary artery disease. Flow-mediated dilation of the brachial artery using Doppler ultrasound is a non-invasive technique for the assessment of endothelial function. The objective of the study was to use the above method to evaluate the pathophysiology of high-fat (HF) intake on endothelial function in a local population. A popular local dish \"nasi-lemak\", a source of high saturated fat content from coconut milk, was chosen to represent a local high-fat meal (LHF). In addition, the effects of a Western high-fat (WHF) (\"McDonald's\") meal and a low-fat (LF) meal control on endothelial function were studied. MATERIALS AND METHODS: The study population consisted of 10 healthy male non-smoker (mean age 22 +/- 2 years) with normal body mass index, normal fasting sugar and lipid profiles. Nitric oxide dependent flow-mediated dilation and nitric oxide independent (GTN) dilation was assessed by Doppler flow in the brachial artery before and 4 hours after each meal on separate occasions by 2 experienced sonographers blinded to the type of meals. RESULTS: The baseline brachial artery size, baseline vessel flow and increase in flow after cuff deflation were similar for each of the six arterial studies. In response to reactive hyperaemia after cuff deflation, the endothelium-dependent dilation was significantly different between the meals. There was a marked decrease in endothelium-dependent dilation after the WHF meal compared to the LF meal (8.6 +/- 2.2% vs. -0.8 +/- 1.1%, P < 0.006). There was also a marked decrease in endothelium-dependent dilation after the LHF meal compared to the LF meal (7.7 +/- 2.1% vs. -0.8 +/- 1.1%, P < 0.001). When comparing between the two HF meals, the change in endothelium-dependent dilation was not significant (7.7 vs. 8.6%, P = 0.678). GTN-induced dilation was not significantly different before and after the LF, WHF or LHF (0.1 +/- 0.5% vs. 0.2 +/- 0.9% vs. 1.3 +/- 0.5%, P = 0.094). CONCLUSION: The results suggest that in a local population, impairment of endothelial function is a possible mechanism in the pathophysiology of atherosclerosis from HF intake, beyond just affecting lipid levels. This effect is observed after both a LHF and a WHF meal intake. This technique to study endothelial function may be a useful non-invasive screening tool in the study of other HF diet choices and provides further information for the education of the influence of dietary choices on atherosclerosis.",
"title": "Impairment of endothelial function--a possible mechanism for atherosclerosis of a high-fat meal intake."
},
{
"docid": "MED-1968",
"text": "Our aim was to determine the effects of increasing amounts of dietary cholesterol (0-710 mg) on the postprandial plasma lipid responses and lipoprotein changes in normolipidemic human subjects. Ten subjects were fed five different test meals in a random order: one meal did not contain fat or cholesterol while the four others contained a fixed amount of lipids (45 g) and 0, 140, 280, and 710 mg cholesterol, respectively. Fasting and post-meal blood samples were obtained for 7 h. Large and small triglyceride-rich lipoproteins (TRL), low density (LDL), and high density (HDL) lipoproteins were isolated. Compared to the no-fat, no-cholesterol meal, the fat-enriched meals raised (P < 0.05) plasma triglycerides, phospholipids, and free cholesterol and lowered cholesteryl esters postprandially. The meals containing zero or 140 mg cholesterol generally elicited comparable postprandial plasma and lipoprotein lipid responses. The meals providing 280 or 710 mg cholesterol significantly increased postprandial plasma phospholipids and large TRL triglycerides and decreased plasma esterified cholesterol. The lipid composition of the large TRLs and the concentrations of the small TRL lipid components were not altered postprandially by cholesterol intake. On the other hand, LDL free cholesterol increased after 3 h, LDL cholesteryl esters dropped after 3 and 7 h, HDL cholesteryl esters dropped after 3 h, and HDL phospholipids increased 7 h after ingesting meals highly enriched in cholesterol. Blood insulin, apoA-I and apoB were not altered postprandially by cholesterol intake. Thus, the data show that ingesting more than 140 mg cholesterol per meal significantly alters the postprandial lipoprotein response in healthy subjects.",
"title": "Effects of increasing amounts of dietary cholesterol on postprandial lipemia and lipoproteins in human subjects."
},
{
"docid": "MED-2253",
"text": "Twenty three adults ingested 203Pb as lead acetate on the 12th hour of a 19 h fast. Retention measured 7 days later in a whole-body counter was 61% and whole-body turnover rates suggested that initial uptake had been considerably greater. Balanced meals eaten with 203Pb reduced lead uptake to 4% and the influence of the food lasted for up to 3 h. The effects of phytate, ethylene-diaminetetra acetate (EDTA), caffeine, alcohol, glucose, a liquid meal and a light snack were tested separately with intermediate results. The effect of a meal was probably largely due to its content of calcium and phosphate salts but lead uptake was probably further reduced by phytate which is plentiful in whole cereals and it was probably increased by a factor in milk. Uptake with skimmed milk was the same as with whole milk and we suggested that the factor was not fat. Comestibles with low mineral and phytate contents reduced lead uptake by intermediate amounts, possibly by stimulation of digestive secretions. The avid uptake of lead during a fast, the large reduction of lead uptake with meals and the likelihood of variations in gastric-emptying rates and dietary habits may be major causes of variation in body burdens of lead in the population.",
"title": "Effects of meals and meal times on uptake of lead from the gastrointestinal tract in humans."
},
{
"docid": "MED-5271",
"text": "OBJECTIVES: This study investigated the postprandial effect of components of the Mediterranean diet on endothelial function, which may be an atherogenic factor. BACKGROUND: The Mediterranean diet, containing olive oil, pasta, fruits, vegetables, fish, and wine, is associated with an unexpectedly low rate of cardiovascular events. The Lyon Diet Heart Study found that a Mediterranean diet, which substituted omega-3-fatty-acid-enriched canola oil for the traditionally consumed omega-9 fatty-acid-rich olive oil, reduced cardiovascular events. METHODS: We fed 10 healthy, normolipidemic subjects five meals containing 900 kcal and 50 g fat. Three meals contained different fat sources: olive oil, canola oil, and salmon. Two olive oil meals also contained antioxidant vitamins (C and E) or foods (balsamic vinegar and salad). We measured serum lipoproteins and glucose and brachial artery flow-mediated vasodilation (FMD), an index of endothelial function, before and 3 h after each meal. RESULTS: All five meals significantly raised serum triglycerides, but did not change other lipoproteins or glucose 3 h postprandially. The olive oil meal reduced FMD 31% (14.3 +/- 4.2% to 9.9 +/- 4.5%, p = 0.008). An inverse correlation was observed between postprandial changes in serum triglycerides and FMD (r = -0.47, p < 0.05). The remaining four meals did not significantly reduce FMD. CONCLUSIONS: In terms of their postprandial effect on endothelial function, the beneficial components of the Mediterranean and Lyon Diet Heart Study diets appear to be antioxidant-rich foods, including vegetables, fruits, and their derivatives such as vinegar, and omega-3-rich fish and canola oils.",
"title": "The postprandial effect of components of the Mediterranean diet on endothelial function."
},
{
"docid": "MED-4318",
"text": "Preliminary data in the literature indicate that iron absorption from a meal may be increased when consumed with low-pH beverages such as cola, and it is also possible that sugar iron complexes may alter iron availability. A randomized, crossover trial was conducted to compare the bioavailability of nonheme iron from a vegetarian pizza meal when consumed with 3 different beverages (cola, diet cola, and mineral water). Sixteen women with serum ferritin concentrations of 11-54 µg/L were recruited and completed the study. The pizza meal contained native iron and added ferric chloride solution as a stable isotope extrinsic label; the total iron content of the meal was ~5.3 mg. Incorporation of iron from the meal into RBC was not affected by the type of drink (9.9% with cola, 9.4% with diet cola, and 9.6% with water). Serum ferritin and plasma hepcidin were correlated (r = 0.66; P<0.001) and both were significant predictors of iron bioavailability, but their combined effect explained only 30% of the inter-individual variation (P<0.001) and illustrates the current lack of understanding of mechanisms responsible for the fine-tuning of iron absorption. Although there was no effect of low-pH drinks on iron bioavailability in healthy women, their effect on absorption of fortification iron that requires solubilization in dilute acid, such as reduced iron, and in individuals with low gastric acid production, such as older people and individuals with Helicobacter pylori infection, warrants further investigation.",
"title": "Low-pH cola beverages do not affect women's iron absorption from a vegetarian meal."
},
{
"docid": "MED-760",
"text": "There is much interest in the potential of dietary antioxidants to attenuate in vivo oxidative stress, but little characterization of the time course of plasma effects exists. Culinary spices have demonstrated potent in vitro antioxidant properties. The objective of this study was to examine whether adding 14 g of a high antioxidant spice blend to a 5060-kJ (1200 kcal) meal exerted significant postprandial effects on markers of plasma antioxidant status and metabolism. Healthy overweight men (n = 6) consumed a control and spiced meal in a randomized crossover design with 1 wk between testing sessions. Blood was sampled prior to the meal and at 30-min intervals for 3.5 h (total of 8 samples). Mixed linear models demonstrated a treatment × time interaction (P < 0.05) for insulin and TG, corresponding with 21 and 31% reductions in postprandial levels with the spiced meal, respectively. Adding spices to the meal significantly increased the ferric reducing antioxidant power, such that postprandial increases following the spiced meal were 2-fold greater than after the control meal (P = 0.009). The hydrophilic oxygen radical absorbance capacity (ORAC) of plasma also was increased by spices (P = 0.02). There were no treatment differences in glucose, total thiols, lipophilic ORAC, or total ORAC. The incorporation of spices into the diet may help normalize postprandial insulin and TG and enhance antioxidant defenses.",
"title": "A High Antioxidant Spice Blend Attenuates Postprandial Insulin and Triglyceride Responses and Increases Some Plasma Measures of Antioxidant Activity in Healthy, Overweight Men"
}
] |
PLAIN-2625
|
Turmeric Curcumin Reprogramming Cancer Cell Death
|
[
{
"docid": "MED-2781",
"text": "Our previous study demonstrated that curcumin, an active compound of Curcuma xanthorrhiza and C. domestica, produces a positive cholekinetic effect. A 20 mg amount of curcumin is capable of contracting the gall bladder by up to 29% within an observation time of 2 h. The aim of the current study was to define the dosage of curcumin capable of producing a 50% contraction of the gall bladder, and to determine if there is a linear relationship between doubling the curcumin dosage and the doubling of gall bladder contraction. A randomised, single-blind, three-phase, crossover-designed examination was carried out on 12 healthy volunteers. Ultrasonography was carried out serially to measure the gall bladder volume. The data obtained was analysed by analysis of variance (ANOVA). The fasting volumes of gall bladders were similar (P > 0.50), with 17.28 +/- 5.47 mL for 20 mg curcumin, 18.34 +/- 3.75 mL for 40 mg and 18.24 +/- 3.72 mL for 80 mg. The percentage decrease in gall bladder volume 2 h after administration of 20, 40 and 80 mg was 34.10 +/- 10.16, 51.15 +/- 8.08 and 72.25 +/- 8.22, respectively, which was significantly different (P < 0.01). On the basis of the present findings, it appears that the dosage of cucumin capable of producing a 50% contraction of the bladder was 40 mg. This study did not show any linear relationship between doubling curcumin dosage and the doubling of gall bladder contraction.",
"title": "Effect of different curcumin dosages on human gall bladder."
},
{
"docid": "MED-2819",
"text": "OBJECTIVES: Curcumin (diferuloylmethane) is the principal biochemical component of the spice turmeric and has been shown to possess potent anti-catabolic, anti-inflammatory and antioxidant, properties. This article aims to provide a summary of the actions of curcumin on articular chondrocytes from the available literature with the use of a text-mining tool. We highlight both the potential benefits and drawbacks of using this chemopreventive agent for treating osteoarthritis (OA). We also explore the recent literature on the molecular mechanisms of curcumin mediated alterations in gene expression mediated via activator protein 1 (AP-1)/nuclear factor-kappa B (NF-kappaB) signalling in chondrocytes, osteoblasts and synovial fibroblasts. METHODS: A computer-aided search of the PubMed/Medline database aided by a text-mining tool to interrogate the ResNet Mammalian database 6.0. RESULTS: Recent work has shown that curcumin protects human chondrocytes from the catabolic actions of interleukin-1 beta (IL-1beta) including matrix metalloproteinase (MMP)-3 up-regulation, inhibition of collagen type II and down-regulation of beta1-integrin expression. Curcumin blocks IL-1beta-induced proteoglycan degradation, AP-1/NF-kappaB signalling, chondrocyte apoptosis and activation of caspase-3. CONCLUSIONS: The available data from published in vitro and in vivo studies suggest that curcumin may be a beneficial complementary treatment for OA in humans and companion animals. Nevertheless, before initiating extensive clinical trials, more basic research is required to improve its solubility, absorption and bioavailability and gain additional information about its safety and efficacy in different species. Once these obstacles have been overcome, curcumin and structurally related biochemicals may become safer and more suitable nutraceutical alternatives to the non-steroidal anti-inflammatory drugs that are currently used for the treatment of OA. Copyright 2009 Osteoarthritis Research Society International. All rights reserved.",
"title": "Biological actions of curcumin on articular chondrocytes."
},
{
"docid": "MED-2825",
"text": "Turmeric, a dried powder derived from the rhizome of Curcuma longa, has been used for centuries in certain parts of the world and has been linked to numerous biological activities including antioxidant, anti-inflammatory, anticancer, antigrowth, anti-arthritic, anti-atherosclerotic, antidepressant, anti-aging, antidiabetic, antimicrobial, wound healing, and memory-enhancing activities. One component of turmeric is curcumin, which has been extensively studied, as indicated by more than 5600 citations, most of which have appeared within the past decade. Recent research has identified numerous chemical entities from turmeric other than curcumin. It is unclear whether all of the activities ascribed to turmeric are due to curcumin or whether other compounds in turmeric can manifest these activities uniquely, additively, or synergistically with curcumin. However, studies have indicated that turmeric oil, present in turmeric, can enhance the bioavailability of curcumin. Studies over the past decade have indicated that curcumin-free turmeric (CFT) components possess numerous biological activities including anti-inflammatory, anticancer, and antidiabetic activities. Elemene derived from turmeric is approved in China for the treatment of cancer. The current review focuses on the anticancer and anti-inflammatory activities exhibited by CFT and by some individual components of turmeric, including turmerin, turmerone, elemene, furanodiene, curdione, bisacurone, cyclocurcumin, calebin A, and germacrone. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",
"title": "Curcumin-free turmeric exhibits anti-inflammatory and anticancer activities: Identification of novel components of turmeric."
},
{
"docid": "MED-4239",
"text": "BACKGROUND: Prostate cancer is the most common solid-tumor cancer in US males but is rare in Asian males. When Asian men adopt the US lifestyle, clinical prostate cancer increases greatly. Epidemiological data from men in the US indicate that regular activity may reduce the risk for prostate cancer. METHODS: Serum was obtained from three groups of similar-aged men, Control, Diet and Exercise, and Exercise alone were used to stimulate LNCaP cells in culture. Growth and apoptosis of tumor cells were measured. Serum samples were also used to measure insulin, IGF-1, IGFBP-1. RESULTS: The Diet and Exercise and the Exercise alone groups had lower serum insulin and IGF-1 but higher IGFBP-1 compared to Controls. LNCaP cell growth was reduced in both groups compared to Control and there was a major increase in apoptosis of tumor cells. CONCLUSIONS: A low-fat diet and/or intensive exercise results in change in serum hormones and growth factors in vivo that can reduce growth and induce apoptosis of LNCaP prostate tumor cells in vitro. Copyright 2003 Wiley-Liss, Inc.",
"title": "A low-fat diet and/or strenuous exercise alters the IGF axis in vivo and reduces prostate tumor cell growth in vitro."
},
{
"docid": "MED-2812",
"text": "Curcumin derived from the tropical plant Curcuma longa has a long history of use as a dietary agent, food preservative, and in traditional Asian medicine. It has been used for centuries to treat biliary disorders, anorexia, cough, diabetic wounds, hepatic disorders, rheumatism, and sinusitis. The preventive and therapeutic properties of curcumin are associated with its antioxidant, anti-inflammatory, and anticancer properties. Extensive research over several decades has attempted to identify the molecular mechanisms of curcumin action. Curcumin modulates numerous molecular targets by altering their gene expression, signaling pathways, or through direct interaction. Curcumin regulates the expression of inflammatory cytokines (e.g., TNF, IL-1), growth factors (e.g., VEGF, EGF, FGF), growth factor receptors (e.g., EGFR, HER-2, AR), enzymes (e.g., COX-2, LOX, MMP9, MAPK, mTOR, Akt), adhesion molecules (e.g., ELAM-1, ICAM-1, VCAM-1), apoptosis related proteins (e.g., Bcl-2, caspases, DR, Fas), and cell cycle proteins (e.g., cyclin D1). Curcumin modulates the activity of several transcription factors (e.g., NF-κB, AP-1, STAT) and their signaling pathways. Based on its ability to affect multiple targets, curcumin has the potential for the prevention and treatment of various diseases including cancers, arthritis, allergies, atherosclerosis, aging, neurodegenerative disease, hepatic disorders, obesity, diabetes, psoriasis, and autoimmune diseases. This review summarizes the molecular mechanisms of modulation of gene expression by curcumin. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.",
"title": "Molecular mechanisms of curcumin action: gene expression."
},
{
"docid": "MED-2604",
"text": "Cancer is a hyperproliferative disorder that is usually treated by chemotherapeutic agents that are toxic not only to tumor cells but also to normal cells, so these agents produce major side effects. In addition, these agents are highly expensive and thus not affordable for most. Moreover, such agents cannot be used for cancer prevention. Traditional medicines are generally free of the deleterious side effects and usually inexpensive. Curcumin, a component of turmeric (Curcuma longa), is one such agent that is safe, affordable, and efficacious. How curcumin kills tumor cells is the focus of this review. We show that curcumin modulates growth of tumor cells through regulation of multiple cell signaling pathways including cell proliferation pathway (cyclin D1, c-myc), cell survival pathway (Bcl-2, Bcl-xL, cFLIP, XIAP, c-IAP1), caspase activation pathway (caspase-8, 3, 9), tumor suppressor pathway (p53, p21) death receptor pathway (DR4, DR5), mitochondrial pathways, and protein kinase pathway (JNK, Akt, and AMPK). How curcumin selectively kills tumor cells, and not normal cells, is also described in detail.",
"title": "Curcumin and Cancer Cells: How Many Ways Can Curry Kill Tumor Cells Selectively?"
},
{
"docid": "MED-2605",
"text": "Curcumin (diferuloylmethane), the yellow pigment in turmeric (Curcuma longa), is known to inhibit proliferation of cancer cells by arresting them at various phases of the cell cycle and to induce apoptosis in tumor cells. Curcumin-induced apoptosis mainly involves the activation of caspase-3 and mitochondria-mediated pathway in various cancer cells of different tissue origin. In the present study, the induction of apoptosis and cytotoxicity by curcumin in colon cancer colo 205 cells was investigated by using flow cytometry. The results demonstrated that curcumin induced cytotoxicity and apoptosis dose- and time-depedently. Curcumin induced the production of reactive oxygen species (ROS) and Ca+2, decreased the levels of mitochondria membrane potential and induced caspase-3 activity. Curcumin also promoted the expression of Bax, cytochrome C, p53 and p21 but inhibited the expression of Bcl-2. These observations suggest that curcumin may have a possible therapeutic potential in colon cancer patients.",
"title": "Curcumin-induced apoptosis of human colon cancer colo 205 cells through the production of ROS, Ca2+ and the activation of caspase-3."
},
{
"docid": "MED-2826",
"text": "Background Curcumin extracts of turmeric are proposed to produce health benefits. To date, human intervention studies have focused mainly on people with existing health problems given high doses of poorly absorbed curcumin. The purpose of the current study was to check whether in healthy people, a low dose of a lipidated curcumin extract could alter wellness-related measures. Methods The present study was conducted in healthy middle aged people (40–60 years old) with a low dose of curcumin (80 mg/day) in a lipidated form expected to have good absorption. Subjects were given either curcumin (N = 19) or placebo (N = 19) for 4 wk. Blood and saliva samples were taken before and after the 4 weeks and analyzed for a variety of blood and saliva measures relevant to health promotion. Results Curcumin, but not placebo, produced the following statistically significant changes: lowering of plasma triglyceride values, lowering of salivary amylase levels, raising of salivary radical scavenging capacities, raising of plasma catalase activities, lowering of plasma beta amyloid protein concentrations, lowering of plasma sICAM readings, increased plasma myeloperoxidase without increased c-reactive protein levels, increased plasma nitric oxide, and decreased plasma alanine amino transferase activities. Conclusion Collectively, these results demonstrate that a low dose of a curcumin-lipid preparation can produce a variety of potentially health promoting effects in healthy middle aged people.",
"title": "Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people"
},
{
"docid": "MED-2794",
"text": "Turmeric, a plant rhizome that is often dried, ground and used as a cooking spice, has also been used medicinally for several thousand years. Curcumin, the phytochemical that gives turmeric its golden color, is responsible for most of the therapeutic effects of turmeric. In recent years curcumin has been studied for its effects on chronic diseases such as diabetes, Alzheimer's, and cancer. Though many researchers are investigating turmeric/curcumin in cancer therapy, there is little epidemiologic information on the effects of turmeric consumption. With limited availability of pharmacologic interventions in many areas of the world, use of turmeric in the diet may help to alleviate some of the disease burden through prevention. Here we provide a brief overview of turmeric consumption in different parts of the world, cancer rates in those regions, possible biochemical mechanisms by which turmeric acts and practical recommendations based on the information available.",
"title": "Dietary turmeric potentially reduces the risk of cancer."
},
{
"docid": "MED-2814",
"text": "Curcumin (diferuloylmethane), an active constituent of turmeric, is a well-described phytochemical, which has been used since ancient times for the treatment of various diseases. The dysregulation of cell signaling pathways by the gradual alteration of regulatory proteins is the root cause of cancers. Curcumin modulates regulatory proteins through various molecular mechanisms. Several research studies have provided in-depth analysis of multiple targets through which curcumin induces protective effects against cancers including gastrointestinal, genitourinary, gynecological, hematological, pulmonary, thymic, brain, breast, and bone. The molecular mechanisms of action of curcumin in treating different types of cancers remain under investigation. The multifaceted role of this dietary agent is mediated through its inhibition of several cell signaling pathways at multiple levels. Curcumin has the ability to inhibit carcinogenicity through the modulation of the cell cycle by binding directly and indirectly to molecular targets including transcription factors (NF-kB, STAT3, β-catenin, and AP-1), growth factors (EGF, PDGF, and VEGF), enzymes (COX-2, iNOS, and MMPs), kinases (cyclin D1, CDKs, Akt, PKC, and AMPK), inflammatory cytokines (TNF, MCP, IL-1, and IL-6), upregulation of proapoptotic (Bax, Bad, and Bak) and downregulation of antiapoptotic proteins (Bcl(2) and Bcl-xL). A variety of animal models and human studies have proven that curcumin is safe and well tolerated even at very high doses. This study elaborates the current understanding of the chemopreventive effects of curcumin through its multiple molecular pathways and highlights its therapeutic value in the treatment and prevention of a wide range of cancers. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.",
"title": "Curcumin in various cancers."
},
{
"docid": "MED-2810",
"text": "Although turmeric (Curcuma longa; an Indian spice) has been described in Ayurveda, as a treatment for inflammatory diseases and is referred by different names in different cultures, the active principle called curcumin or diferuloylmethane, a yellow pigment present in turmeric (curry powder) has been shown to exhibit numerous activities. Extensive research over the last half century has revealed several important functions of curcumin. It binds to a variety of proteins and inhibits the activity of various kinases. By modulating the activation of various transcription factors, curcumin regulates the expression of inflammatory enzymes, cytokines, adhesion molecules, and cell survival proteins. Curcumin also downregulates cyclin D1, cyclin E and MDM2; and upregulates p21, p27, and p53. Various preclinical cell culture and animal studies suggest that curcumin has potential as an antiproliferative, anti-invasive, and antiangiogenic agent; as a mediator of chemoresistance and radioresistance; as a chemopreventive agent; and as a therapeutic agent in wound healing, diabetes, Alzheimer disease, Parkinson disease, cardiovascular disease, pulmonary disease, and arthritis. Pilot phase I clinical trials have shown curcumin to be safe even when consumed at a daily dose of 12g for 3 months. Other clinical trials suggest a potential therapeutic role for curcumin in diseases such as familial adenomatous polyposis, inflammatory bowel disease, ulcerative colitis, colon cancer, pancreatic cancer, hypercholesteremia, atherosclerosis, pancreatitis, psoriasis, chronic anterior uveitis and arthritis. Thus, curcumin, a spice once relegated to the kitchen shelf, has moved into the clinic and may prove to be \"Curecumin\".",
"title": "Curcumin as \"Curecumin\": from kitchen to clinic."
},
{
"docid": "MED-2599",
"text": "Curcumin exhibits anti-inflammatory and antitumor activities. Although its functional mechanism has not been elucidated so far, numerous studies have shown that curcumin induces apoptosis in cancer cells. In the present study, we show that subtoxic concentrations of curcumin sensitize human renal cancer cells to the tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-mediated apoptosis. This apoptosis induced by the combination of curcumin and TRAIL is not interrupted by Bcl-2 overexpression. We found that treatment with curcumin significantly induces death receptor 5 (DR5) expression both at its mRNA and protein levels, accompanying the generation of the reactive oxygen species (ROS). Not only the pretreatment with N-acetylcystine but also the ectopic expression of peroxiredoxin II, an antioxidative protein, dramatically inhibited the apoptosis induced by curcumin and TRAIL in combination, blocking the curcumin-mediated DR5 upregulation. Taken together, the present study demonstrates that curcumin enhances TRAIL-induced apoptosis by ROS-mediated DR5 upregulation.",
"title": "Curcumin sensitizes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through reactive oxygen species-mediated upre..."
},
{
"docid": "MED-5337",
"text": "PURPOSE: Men with prostate cancer are often advised to make changes in diet and lifestyle, although the impact of these changes has not been well documented. Therefore, we evaluated the effects of comprehensive lifestyle changes on prostate specific antigen (PSA), treatment trends and serum stimulated LNCaP cell growth in men with early, biopsy proven prostate cancer after 1 year. MATERIALS AND METHODS: Patient recruitment was limited to men who had chosen not to undergo any conventional treatment, which provided an unusual opportunity to have a nonintervention randomized control group to avoid the confounding effects of interventions such as radiation, surgery or androgen deprivation therapy. A total of 93 volunteers with serum PSA 4 to 10 ng/ml and cancer Gleason scores less than 7 were randomly assigned to an experimental group that was asked to make comprehensive lifestyle changes or to a usual care control group. RESULTS: None of the experimental group patients but 6 control patients underwent conventional treatment due to an increase in PSA and/or progression of disease on magnetic resonance imaging. PSA decreased 4% in the experimental group but increased 6% in the control group (p = 0.016). The growth of LNCaP prostate cancer cells (American Type Culture Collection, Manassas, Virginia) was inhibited almost 8 times more by serum from the experimental than from the control group (70% vs 9%, p <0.001). Changes in serum PSA and also in LNCaP cell growth were significantly associated with the degree of change in diet and lifestyle. CONCLUSIONS: Intensive lifestyle changes may affect the progression of early, low grade prostate cancer in men. Further studies and longer term followup are warranted.",
"title": "Intensive lifestyle changes may affect the progression of prostate cancer."
},
{
"docid": "MED-2805",
"text": "Obesity is a significant risk factor for developing osteoarthritis in weight-bearing and non-weight-bearing joints. Although the pathogenesis of obesity-associated osteoarthritis is not completely understood, recent studies indicate that pro-inflammatory metabolic factors contribute to an increase in osteoarthritis risk. Adipose tissue, and in particular infrapatellar fat, is a local source of pro-inflammatory mediators that are increased with obesity and have been shown to increase cartilage degradation in cell and tissue culture models. One adipokine in particular, leptin, may be a critical mediator of obesity-associated osteoarthritis via synergistic actions with other inflammatory cytokines. Biomechanical factors may also increase the risk of osteoarthritis by activating cellular inflammation and promoting oxidative stress. However, some types of biomechanical stimulation, such as physiologic cyclic loading, inhibit inflammation and protect against cartilage degradation. A high percentage of obese individuals with knee osteoarthritis are sedentary, suggesting that a lack of physical activity may increase the susceptibility to inflammation. A more comprehensive approach to understanding how obesity alters daily biomechanical exposures within joint tissues may provide new insight into the protective and damaging effects of biomechanical factors on inflammation in osteoarthritis.",
"title": "Pathobiology of obesity and osteoarthritis: integrating biomechanics and inflammation"
},
{
"docid": "MED-2815",
"text": "Curcumin, an active polyphenol of the golden spice turmeric, is a highly pleiotropic molecule with the potential to modulate the biological activity of a number of signaling molecules. Traditionally, this polyphenol has been used in Asian countries to treat such human ailments as acne, psoriasis, dermatitis, and rash. Recent studies have indicated that curcumin can target newly identified signaling pathways including those associated with microRNA, cancer stem cells, and autophagy. Extensive research from preclinical and clinical studies has delineated the molecular basis for the pharmaceutical uses of this polyphenol against cancer, pulmonary diseases, neurological diseases, liver diseases, metabolic diseases, autoimmune diseases, cardiovascular diseases, and numerous other chronic diseases. Multiple studies have indicated the safety and efficacy of curcumin in numerous animals including rodents, monkeys, horses, rabbits, and cats and have provided a solid basis for evaluating its safety and efficacy in humans. To date, more than 65 human clinical trials of curcumin, which included more than 1000 patients, have been completed, and as many as 35 clinical trials are underway. Curcumin is now used as a supplement in several countries including the United States, India, Japan, Korea, Thailand, China, Turkey, South Africa, Nepal, and Pakistan. In this review, we provide evidence for the pharmaceutical uses of curcumin for various diseases. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.",
"title": "Curcumin, a component of turmeric: from farm to pharmacy."
},
{
"docid": "MED-2802",
"text": "OBJECTIVE: The objective of this study was to determine the efficacy and safety of Curcuma domestica extracts in pain reduction and functional improvement in patients with knee osteoarthritis. STUDY DESIGN AND SETTING: The design and setting were a randomized controlled study at a university hospital in Bangkok, Thailand. METHODS: One-hundred and seven (107) patients with primary knee osteoarthritis (OA) with pain score of > or =5 were randomized to receive ibuprofen 800 mg per day or C. domestica extracts 2 g per day for 6 weeks. The main outcomes were improvement in pain on level walking, pain on stairs, and functions of knee assessed by time spent during 100-m walk and going up and down a flight of stairs. The adverse events were also recorded. RESULTS: Fifty-two (52) and 55 patients were randomized to C. domestica extracts and ibuprofen groups, respectively. Baseline characteristics of the patients in both groups were not different. The mean scores of the aforementioned outcomes at weeks 0, 2, 4, and 6 were significantly improved when compared with the baseline values in both groups. There was no difference in those parameters between the patients receiving ibuprofen and C. domestica extracts, except pain on stairs (p = 0.016). No significant difference of adverse events between both groups was found (33.3% versus 44.2%, p = 0.36 in C. domestica extracts and ibuprofen groups, respectively). CONCLUSIONS: C. domestica extracts seem to be similarly efficacious and safe as ibuprofen for the treatment of knee OA.",
"title": "Efficacy and safety of Curcuma domestica extracts in patients with knee osteoarthritis."
},
{
"docid": "MED-2813",
"text": "The use of turmeric, derived from the root of the plant Curcuma longa, for treatment of different inflammatory diseases has been described in Ayurveda and in traditional Chinese medicine for thousands of years. The active component of turmeric responsible for this activity, curcumin, was identified almost two centuries ago. Modern science has revealed that curcumin mediates its effects by modulation of several important molecular targets, including transcription factors (e.g., NF-kappaB, AP-1, Egr-1, beta-catenin, and PPAR-gamma), enzymes (e.g., COX2, 5-LOX, iNOS, and hemeoxygenase-1), cell cycle proteins (e.g., cyclin D1 and p21), cytokines (e.g., TNF, IL-1, IL-6, and chemokines), receptors (e.g., EGFR and HER2), and cell surface adhesion molecules. Because it can modulate the expression of these targets, curcumin is now being used to treat cancer, arthritis, diabetes, Crohn's disease, cardiovascular diseases, osteoporosis, Alzheimer's disease, psoriasis, and other pathologies. Interestingly, 6-gingerol, a natural analog of curcumin derived from the root of ginger (Zingiber officinalis), exhibits a biologic activity profile similar to that of curcumin. The efficacy, pharmacologic safety, and cost effectiveness of curcuminoids prompt us to \"get back to our roots.\"",
"title": "Curcumin: getting back to the roots."
},
{
"docid": "MED-2583",
"text": "Inositol hexaphosphate (IP(6)), a naturally polyphosphorylated carbohydrate, has been reported to have significant in vivo and in vitro anticancer activity against numerous tumours, such as colon, prostate, breast, liver and rhabdomyosarcomas. To confirm this activity in haematological malignancies and to characterize some of the mechanisms of IP(6) action, we analysed its effects on human leukaemic cell lines and fresh chronic myelogenous leukaemia (CML) progenitor cells using a combined cellular and molecular approach. IP(6) had a dose-dependent cytotoxic effect on all of the evaluated cell lines, with accumulation in the G2M phase in two out of five cell lines tested. At the molecular level, cDNA microarray analysis after IP(6) exposure showed an extensive downmodulation of genes involved in transcription and cell cycle regulation and a coherent upregulation of cell cycle inhibitors. Furthermore, IP(6) treatment of fresh leukaemic samples of bone marrow CD34+ CML progenitor cells significantly inhibited granulocyte-macrophage colony-forming unit (CFU-GM) formation (P = 0.0062) in comparison to normal bone marrow specimens, which were not affected. No differentiating effect on HL60 cells was observed. Taken together, our results confirm the antiproliferative activity of IP(6) and suggest that it may have a specific antitumour effect also in chronic myeloid leukaemias, via active gene modulation.",
"title": "Effect of inositol hexaphosphate (IP(6)) on human normal and leukaemic haematopoietic cells."
},
{
"docid": "MED-2786",
"text": "Alzheimer's disease (AD) is the most common form of dementia. There is limited choice in modern therapeutics, and drugs available have limited success with multiple side effects in addition to high cost. Hence, newer and alternate treatment options are being explored for effective and safer therapeutic targets to address AD. Turmeric possesses multiple medicinal uses including treatment for AD. Curcuminoids, a mixture of curcumin, demethoxycurcumin, and bisdemethoxycurcumin, are vital constituents of turmeric. It is generally believed that curcumin is the most important constituent of the curcuminoid mixture that contributes to the pharmacological profile of parent curcuminoid mixture or turmeric. A careful literature study reveals that the other two constituents of the curcuminoid mixture also contribute significantly to the effectiveness of curcuminoids in AD. Therefore, it is emphasized in this review that each component of the curcuminoid mixture plays a distinct role in making curcuminoid mixture useful in AD, and hence, the curcuminoid mixture represents turmeric in its medicinal value better than curcumin alone. The progress in understanding the disease etiology demands a multiple-site-targeted therapy, and the curcuminoid mixture of all components, each with different merits, makes this mixture more promising in combating the challenging disease. Copyright © 2013 John Wiley & Sons, Ltd.",
"title": "Therapeutic potential of turmeric in Alzheimer's disease: curcumin or curcuminoids?"
},
{
"docid": "MED-2809",
"text": "Extensive research over the past half century has shown that curcumin (diferuloylmethane), a component of the golden spice turmeric (Curcuma longa), can modulate multiple cell signaling pathways. Extensive clinical trials over the past quarter century have addressed the pharmacokinetics, safety, and efficacy of this nutraceutical against numerous diseases in humans. Some promising effects have been observed in patients with various pro-inflammatory diseases including cancer, cardiovascular disease, arthritis, uveitis, ulcerative proctitis, Crohn’s disease, ulcerative colitis, irritable bowel disease, tropical pancreatitis, peptic ulcer, gastric ulcer, idiopathic orbital inflammatory pseudotumor, oral lichen planus, gastric inflammation, vitiligo, psoriasis, acute coronary syndrome, atherosclerosis, diabetes, diabetic nephropathy, diabetic microangiopathy, lupus nephritis, renal conditions, acquired immunodeficiency syndrome, β-thalassemia, biliary dyskinesia, Dejerine-Sottas disease, cholecystitis, and chronic bacterial prostatitis. Curcumin has also shown protection against hepatic conditions, chronic arsenic exposure, and alcohol intoxication. Dose-escalating studies have indicated the safety of curcumin at doses as high as 12 g/day over 3 months. Curcumin’s pleiotropic activities emanate from its ability to modulate numerous signaling molecules such as pro-inflammatory cytokines, apoptotic proteins, NF–κB, cyclooxygenase-2, 5-LOX, STAT3, C-reactive protein, prostaglandin E2, prostate-specific antigen, adhesion molecules, phosphorylase kinase, transforming growth factor-β, triglyceride, ET-1, creatinine, HO-1, AST, and ALT in human participants. In clinical trials, curcumin has been used either alone or in combination with other agents. Various formulations of curcumin, including nanoparticles, liposomal encapsulation, emulsions, capsules, tablets, and powder, have been examined. In this review, we discuss in detail the various human diseases in which the effect of curcumin has been investigated.",
"title": "Therapeutic Roles of Curcumin: Lessons Learned from Clinical Trials"
},
{
"docid": "MED-4220",
"text": "OBJECTIVE: Accumulating evidence indicates that prostate cancer is associated with high levels of serum IGF-I. This study was conducted to determine whether a low-fat diet and exercise (DE) intervention may modulate the IGF axis and reduce prostate cancer cell growth in vitro. METHODS: Fasting serum was obtained from 14 men (age 60 +/- 3 years) participating in an 11-day DE program and from eight similarly aged men who had followed the DE program for 14.2 +/- 1.7 years (long-term). Insulin, IGF-I, IGFBP-1, and IGFBP-3 were measured by ELISA, and serum was used to stimulate LNCaP cell growth in vitro. RESULTS: Serum IGF-I levels decreased by 20% while IGFBP-1 increased by 53% after 11-day DE. In the long-term group, IGF-I was 55% lower, while IGFBP-1 was 150% higher relative to baseline. Serum insulin decreased by 25% after 11-day DE and was 68% lower in the long-term group, relative to baseline. No changes in serum IGFBP-3 were observed. Serum-stimulated LNCaP cell growth was reduced by 30% in post-11-day serum and by 44% in long-term serum relative to baseline. LNCaP cells incubated with post-DE serum showed increased apoptosis/ necrosis, compared to baseline. CONCLUSIONS: A low-fat diet and exercise intervention induces in-vivo changes in the circulating IGF axis and is associated with reduced growth and enhanced apoptosis/necrosis of LNCaP tumor cells in vitro.",
"title": "Effect of diet and exercise on serum insulin, IGF-I, and IGFBP-1 levels and growth of LNCaP cells in vitro (United States)."
},
{
"docid": "MED-2822",
"text": "Curcumin is known to possess potent antiinflammatory and antiarthritic properties. This pilot clinical study evaluated the safety and effectiveness of curcumin alone, and in combination with diclofenac sodium in patients with active rheumatoid arthritis (RA). Forty-five patients diagnosed with RA were randomized into three groups with patients receiving curcumin (500 mg) and diclofenac sodium (50 mg) alone or their combination. The primary endpoints were reduction in Disease Activity Score (DAS) 28. The secondary endpoints included American College of Rheumatology (ACR) criteria for reduction in tenderness and swelling of joint scores. Patients in all three treatment groups showed statistically significant changes in their DAS scores. Interestingly, the curcumin group showed the highest percentage of improvement in overall DAS and ACR scores (ACR 20, 50 and 70) and these scores were significantly better than the patients in the diclofenac sodium group. More importantly, curcumin treatment was found to be safe and did not relate with any adverse events. Our study provides the first evidence for the safety and superiority of curcumin treatment in patients with active RA, and highlights the need for future large-scale trials to validate these findings in patients with RA and other arthritic conditions. Copyright © 2012 John Wiley & Sons, Ltd.",
"title": "A randomized, pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis."
},
{
"docid": "MED-2793",
"text": "Piperine, a major active component of black and long peppers, has been reported to enhance drug bioavailability. The present studies were aimed at understanding the interaction of piperine with enzymatic drug biotransforming reactions in hepatic tissue in vitro and in vivo. Piperine inhibited arylhydrocarbon hydroxylation, ethylmorphine-N-demethylation, 7-ethoxycoumarin-O-deethylation and 3-hydroxy-benzo(a)pyrene glucuronidation in rat postmitochondrial supernatant in vitro in a dose-dependent manner. Piperine inhibition of these reactions in postmitochondrial supernatant from 3-methylcholanthrene- and phenobarbital-treated rats was similar to the controls. Inhibition by piperine of arylhydrocarbon hydroxylase (AHH) from 3-methylcholanthrene-treated rats was comparable to that observed with 7,8-benzoflavone. Piperine caused noncompetitive inhibition of hepatic microsomal AHH from the untreated and 3-methylcholanthrene-treated rats with a Ki of 30 microM which was close to the apparent Km of AHH observed in the controls. Similarly, the kinetics of inhibition of ethylmorphine-N-demethylase from control rat liver microsomes exhibited noncompetitive inhibition with an apparent Km of 0.8 mM and Ki of 35 microM. These studies demonstrated that piperine is a nonspecific inhibitor of drug metabolism which shows little discrimination between different cytochrome P-450 forms. Oral administration of piperine in rats strongly inhibited the hepatic AHH and UDP-glucuronyltransferase activities. The maximal inhibition of AHH observed within 1 hr restored to normal value in 6 hr. Pretreatment with piperine prolonged hexobarbital sleeping time and zoxazolamine paralysis time in mice at half the dose of SKF-525A. These results demonstrate that piperine is a potent inhibitor of drug metabolism.",
"title": "Biochemical basis of enhanced drug bioavailability by piperine: evidence that piperine is a potent inhibitor of drug metabolism."
},
{
"docid": "MED-2601",
"text": "It has been reported that curcumin inhibited various types of cancer cells in vitro and in vivo. However, mechanisms of curcumin-inhibited cell growth and -induced apoptosis in human non-small cell lung cancer cells (NCI-H460) still remain unclear. In this study, NCI-H460 cells were treated with curcumin to determine its anticancer activity. Different concentrations of curcumin were used for different durations in NCI-H460 cells and the subsequent changes in the cell morphology, viability, cell cycle, mRNA and protein expressions were determined. Curcumin induced apoptotic morphologic changes in NCI-H460 cells in a dose-dependent manner. After curcumin treatment, BAX and BAD were up-regulated, BCL-2, BCL-X(L) and XIAP were down-regulated. In addition, reactive oxygen species (ROS), intracellular Ca(2+) and endoplasmic reticulum (ER) stress were increased in NCI-H460 cells after exposure to curcumin. These signals led to a loss of mitochondrial membrane potential (Delta Psi(m)) and culminated in caspase-3 activation. Curcumin-induced apoptosis was also stimulated through the FAS/caspase-8 (extrinsic) pathway and ER stress proteins, growth arrest- and DNA damage-inducible gene 153 (GADD153) and glucose-regulated protein 78 (GRP78) were activated in the NCI-H460 cells. Apoptotic cell death induced by curcumin was significantly reversed by pretreatment with ROS scavenger or caspase-8 inhibitor. Furthermore, the NCI-H460 cells tended to be arrested at the G(2)/M cell cycle stage after curcumin treatment and down-regulation of cyclin-dependent kinase 1 (CDK1) may be involved. In summary, curcumin exerts its anticancer effects on lung cancer NCI-H460 cells through apoptosis or cell cycle arrest.",
"title": "Curcumin induces apoptosis in human non-small cell lung cancer NCI-H460 cells through ER stress and caspase cascade- and mitochondria-dependent pat..."
},
{
"docid": "MED-4543",
"text": "Phyllanthus emblica Linn. (PE) is a medicinal fruit used in many Asian traditional medicine systems for the treatment of various diseases including cancer. The present study tested the potential anticancer effects of aqueous extract of PE in four ways: (1) against cancer cell lines, (2) in vitro apoptosis, (3) mouse skin tumourigenesis and (4) in vitro invasiveness. The PE extract at 50-100 microg/mL significantly inhibited cell growth of six human cancer cell lines, A549 (lung), HepG2 (liver), HeLa (cervical), MDA-MB-231 (breast), SK-OV3 (ovarian) and SW620 (colorectal). However, the extract was not toxic against MRC5 (normal lung fibroblast). Apoptosis in HeLa cells was also observed as PE extract caused DNA fragmentation and increased activity of caspase-3/7 and caspase-8, but not caspase-9, and up-regulation of the Fas protein indicating a death receptor-mediated mechanism of apoptosis. Treatment of PE extract on mouse skin resulted in over 50% reduction of tumour numbers and volumes in animals treated with DMBA/TPA. Lastly, 25 and 50 microg/mL of PE extract inhibited invasiveness of MDA-MB-231 cells in the in vitro Matrigel invasion assay. These results suggest P. emblica exhibits anticancer activity against selected cancer cells, and warrants further study as a possible chemopreventive and antiinvasive agent. Copyright 2010 John Wiley & Sons, Ltd.",
"title": "Antitumour effects of Phyllanthus emblica L.: induction of cancer cell apoptosis and inhibition of in vivo tumour promotion and in vitro invasion o..."
},
{
"docid": "MED-2585",
"text": "Inositol hexaphosphate (IP6) is a naturally occurring polyphosphorylated carbohydrate that is present in substantial amounts in almost all plant and mammalian cells. It was recently recognized to possess multiple biological functions. A striking anticancer effect of IP6 was demonstrated in different experimental models. Inositol is also a natural constituent possessing moderate anticancer activity. The most consistent and best anticancer results were obtained from the combination of IP6 plus inositol. In addition to reducing cell proliferation, IP6 increases differentiation of malignant cells, often resulting in a reversion to normal phenotype. Exogenously administered IP6 is rapidly taken into the cells and dephosphorylated to lower-phosphate inositol phosphates, which further interfere with signal transduction pathways and cell cycle arrest. Enhanced immunity and antioxidant properties can also contribute to tumor cell destruction. However, the molecular mechanisms underlying this anticancer action are not fully understood. Because it is abundantly present in regular diet, efficiently absorbed from the gastrointestinal tract, and safe, IP6 holds great promise in our strategies for the prevention and treatment of cancer. IP6 plus inositol enhances the anticancer effect of conventional chemotherapy, controls cancer metastases, and improves the quality of life, as shown in a pilot clinical trial. The data strongly argue for the use of IP6 plus inositol in our strategies for cancer prevention and treatment. However, the effectiveness and safety of IP6 plus inositol at therapeutic doses needs to be determined in phase I and phase II clinical trials in humans.",
"title": "Cancer inhibition by inositol hexaphosphate (IP6) and inositol: from laboratory to clinic."
},
{
"docid": "MED-2572",
"text": "In traditional cultures, balancing health with a balanced lifestyle was a core belief. The diseases of modern civilization were rare. Indigenous people have patterns of illness very different from Western civilization; yet, they rapidly develop diseases once exposed to Western foods and lifestyles. Food and medicine were interwoven. All cultures used special or functional foods to prevent disease. Food could be used at different times either as food or medicine. Foods, cultivation, and cooking methods maximized community health and well-being. With methods passed down through generations, cooking processes were utilized that enhanced mineral and nutrient bioavailability. This article focuses on what researchers observed about the food traditions of indigenous people, their disease patterns, the use of specific foods, and the environmental factors that affect people who still eat traditional foods.",
"title": "Traditional non-Western diets."
},
{
"docid": "MED-2820",
"text": "Scope The incidence of cancer is significantly lower in regions where turmeric is heavily consumed. Whether lower cancer incidence is due to turmeric was investigated by examining its effects on tumor cell proliferation, on pro-inflammatory transcription factors NF-κB and STAT3, and on associated gene products. Methods and results Cell proliferation and cell cytotoxicity were measured by the MTT method, NF-κB activity by EMSA, protein expression by Western blot analysis, ROS generation by FACS analysis, and osteoclastogenesis by TRAP assay. Turmeric inhibited NF-κB activation and down-regulated NF-κB-regulated gene products linked to survival (Bcl-2, cFLIP, XIAP, and cIAP1), proliferation (cyclin D1 and c-Myc), and metastasis (CXCR4) of cancer cells. The spice suppressed the activation of STAT3, and induced the death receptors (DR)4 and DR5. Turmeric enhanced the production of ROS, and suppressed the growth of tumor cell lines. Furthermore, turmeric sensitized the tumor cells to chemotherapeutic agents capecitabine and taxol. Turmeric was found to be more potent than pure curcumin for cell growth inhibition. Turmeric also inhibited NF-κB activation induced by RANKL that correlated with the suppression of osteoclastogenesis. Conclusion Our results indicate that turmeric can effectively block the proliferation of tumor cells through the suppression of NF-κB and STAT3 pathways.",
"title": "Turmeric (Curcuma longa) inhibits inflammatory nuclear factor (NF)-κB and NF-κB-regulated gene products and induces death receptors leading to suppressed proliferation, induced chemosensitization, and suppressed osteoclastogenesis"
},
{
"docid": "MED-2787",
"text": "BACKGROUND: The extract of medicinal plants containing curcumin is traditionally believed to have a positive contraction effect on the human gall-bladder. AIMS: To compare the effect of 20 mg curcumin or placebo on the gall-bladder volume of healthy volunteers. METHODS: A randomized, double blind and crossover design study was carried out in 12 healthy volunteers (seven males and five females). Ultrasonography examination was carried out serially to measure the gall-bladder volume. The data obtained was analysed by paired Student's t-test. RESULTS: The fasting gall-bladder volumes of 15.74 +/- 4.29 mL on curcumin and 15.98 +/- 4.08 mL on placebo were similar (P > 0.20). The gall-bladder volume was reduced within the period after curcumin administration. The percentage of gall-bladder volume reduction at 0.5, 1.0, 1.5 and 2.0 h after 20 mg curcumin administration were 11.8 +/- 6.9, 16.8 +/- 7.4, 22.0 +/- 8.5 and 29. 3 +/- 8.3%, respectively, which was statistically significant compared to placebo. CONCLUSION: On the basis of the present findings, it appears that curcumin induces contraction of the human gall-bladder.",
"title": "The effect of curcumin and placebo on human gall-bladder function: an ultrasound study."
},
{
"docid": "MED-2790",
"text": "Vasa (Adhatoda vasica Linn.) is a well known and easily available drug in almost all the seasons. Easy availability of any drug gains popularity among physicians as well as pharmaceuticals and this is the reason why almost every Kalpana of Vasa is found described in the Ayurvedika text. The different dosage forms of Vasa like Kvatha, Avaleha, Sneha, and Sandhana have been used for the treatment of Shwasa Roga. A number of research studies have been performed on different formulations of Vasa and its effect on Shwasa Roga. Therefore, a review study has been carried out on the Vasa extract, Vasa Avaleha (prepared from Svarasa and Kvatha), Vasa Ghrita, Vasarishta, and Vasakasava on Shwasa Roga, to know which formulation is better. It was found in the review that Vasa Ghana, Vasa Ghrita (1), and Vasa Avaleha have shown good results on Tamaka Shwasa.",
"title": "A clinical review of different formulations of Vasa (Adhatoda vasica) on Tamaka Shwasa (asthma)"
},
{
"docid": "MED-2777",
"text": "BACKGROUND: Gout, an inflammatory arthritis, reportedly afflicts more than 2 million men and women in the United States. Previous reports have suggested an association between gout and kidney stone disease; however, these studies did not adjust for such important potential confounders as obesity and the presence of hypertension. To our knowledge, no published study has examined the independent association between gout and kidney stone disease. METHODS: We used a national probability sample of the US population to determine the independent association between reported gout and history of kidney stone disease. RESULTS: Among men and women 20 years and older, 5.6% (10 million) reported the previous passage of a kidney stone and 2.7% (5.1 million) reported a diagnosis of gout by a physician. Moreover, 8.6% of individuals who reported the passage of a kidney stone on two or more occasions had a history of gout. Conversely, the prevalence of previous kidney stones in subjects with reported gout was 13.9%. In the age-adjusted model, gout was associated with an increased odds ratio (OR) for previous kidney stones (OR, 1.97; 95% confidence interval [CI], 1.37 to 2.83). After further adjustment for sex, race, body mass index, and presence of hypertension, the OR for previous kidney stones in individuals with gout decreased to 1.49 (95% CI, 1.04 to 2.14). CONCLUSION: Showing an independent association between kidney stone disease and gout strongly suggests that they share common underlying pathophysiological mechanisms. Identification of these mechanisms may lead to improved preventive strategies for both conditions. Copyright 2002 by the National Kidney Foundation, Inc.",
"title": "The association between gout and nephrolithiasis: the National Health and Nutrition Examination Survey III, 1988-1994."
},
{
"docid": "MED-4612",
"text": "Amino acids modulate the secretion of both insulin and glucagon; the composition of dietary protein therefore has the potential to influence the balance of glucagon and insulin activity. Soy protein, as well as many other vegan proteins, are higher in non-essential amino acids than most animal-derived food proteins, and as a result should preferentially favor glucagon production. Acting on hepatocytes, glucagon promotes (and insulin inhibits) cAMP-dependent mechanisms that down-regulate lipogenic enzymes and cholesterol synthesis, while up-regulating hepatic LDL receptors and production of the IGF-I antagonist IGFBP-1. The insulin-sensitizing properties of many vegan diets--high in fiber, low in saturated fat--should amplify these effects by down-regulating insulin secretion. Additionally, the relatively low essential amino acid content of some vegan diets may decrease hepatic IGF-I synthesis. Thus, diets featuring vegan proteins can be expected to lower elevated serum lipid levels, promote weight loss, and decrease circulating IGF-I activity. The latter effect should impede cancer induction (as is seen in animal studies with soy protein), lessen neutrophil-mediated inflammatory damage, and slow growth and maturation in children. In fact, vegans tend to have low serum lipids, lean physiques, shorter stature, later puberty, and decreased risk for certain prominent 'Western' cancers; a vegan diet has documented clinical efficacy in rheumatoid arthritis. Low-fat vegan diets may be especially protective in regard to cancers linked to insulin resistance--namely, breast and colon cancer--as well as prostate cancer; conversely, the high IGF-I activity associated with heavy ingestion of animal products may be largely responsible for the epidemic of 'Western' cancers in wealthy societies. Increased phytochemical intake is also likely to contribute to the reduction of cancer risk in vegans. Regression of coronary stenoses has been documented during low-fat vegan diets coupled with exercise training; such regimens also tend to markedly improve diabetic control and lower elevated blood pressure. Risk of many other degenerative disorders may be decreased in vegans, although reduced growth factor activity may be responsible for an increased risk of hemorrhagic stroke. By altering the glucagon/insulin balance, it is conceivable that supplemental intakes of key non-essential amino acids could enable omnivores to enjoy some of the health advantages of a vegan diet. An unnecessarily high intake of essential amino acids--either in the absolute sense or relative to total dietary protein--may prove to be as grave a risk factor for 'Western' degenerative diseases as is excessive fat intake.",
"title": "Vegan proteins may reduce risk of cancer, obesity, and cardiovascular disease by promoting increased glucagon activity."
},
{
"docid": "MED-2831",
"text": "TNFs are major mediators of inflammation and inflammation-related diseases, hence, the United States Food and Drug Administration (FDA) has approved the use of blockers of the cytokine, TNF-α, for the treatment of osteoarthritis, inflammatory bowel disease, psoriasis and ankylosis. These drugs include the chimeric TNF antibody (infliximab), humanized TNF-α antibody (Humira) and soluble TNF receptor-II (Enbrel) and are associated with a total cumulative market value of more than $20 billion a year. As well as being expensive ($15 000–20 000 per person per year), these drugs have to be injected and have enough adverse effects to be given a black label warning by the FDA. In the current report, we describe an alternative, curcumin (diferuloylmethane), a component of turmeric (Curcuma longa) that is very inexpensive, orally bioavailable and highly safe in humans, yet can block TNF-α action and production in in vitro models, in animal models and in humans. In addition, we provide evidence for curcumin's activities against all of the diseases for which TNF blockers are currently being used. Mechanisms by which curcumin inhibits the production and the cell signalling pathways activated by this cytokine are also discussed. With health-care costs and safety being major issues today, this golden spice may help provide the solution. Linked Articles This article is part of a themed section on Emerging Therapeutic Aspects in Oncology. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.169.issue-8",
"title": "Curcumin: an orally bioavailable blocker of TNF and other pro-inflammatory biomarkers"
},
{
"docid": "MED-2574",
"text": "Inositol hexaphosphate (IP(6)) is a naturally occurring polyphosphorylated carbohydrate, abundantly present in many plant sources and in certain high-fiber diets, such as cereals and legumes. In addition to being found in plants, IP(6) is contained in almost all mammalian cells, although in much smaller amounts, where it is important in regulating vital cellular functions such as signal transduction, cell proliferation, and differentiation. For a long time IP(6) has been recognized as a natural antioxidant. Recently IP(6) has received much attention for its role in cancer prevention and control of experimental tumor growth, progression, and metastasis. In addition, IP(6) possesses other significant benefits for human health, such as the ability to enhance immune system, prevent pathological calcification and kidney stone formation, lower elevated serum cholesterol, and reduce pathological platelet activity. In this review we show the efficacy and discuss some of the molecular mechanisms that govern the action of this dietary agent. Exogenously administered IP(6) is rapidly taken up into cells and dephosphorylated to lower inositol phosphates, which further affect signal transduction pathways resulting in cell cycle arrest. A striking anticancer action of IP(6) was demonstrated in different experimental models. In addition to reducing cell proliferation, IP(6) also induces differentiation of malignant cells. Enhanced immunity and antioxidant properties also contribute to tumor cell destruction. Preliminary studies in humans show that IP(6) and inositol, the precursor molecule of IP(6), appear to enhance the anticancer effect of conventional chemotherapy, control cancer metastases, and improve quality of life. Because it is abundantly present in regular diet, efficiently absorbed from the gastrointestinal tract, and safe, IP(6) + inositol holds great promise in our strategies for cancer prevention and therapy. There is clearly enough evidence to justify the initiation of full-scale clinical trials in humans.",
"title": "Protection against cancer by dietary IP6 and inositol."
},
{
"docid": "MED-4114",
"text": "Induced apoptosis of autoreactive T-lymphocyte precursors in the thymus is crucial for the prevention of autoimmune disorders. IGF-I and prolactin, which are lymphocyte growth factors, may have the potential to suppress apoptosis in thymocytes and thus encourage autoimmunity; conversely, dietary fish oil rich in omega-3 fats appears to upregulate apoptosis in lymphocytes. Since whole-food vegan diets may downregulate systemic IGF-I activity, it is proposed that such a diet, in conjunction with fish oil supplementation and treatment with dopamine agonists capable of suppressing prolactin secretion, may have utility for treating and preventing autoimmune disorders. This prediction is consistent with the extreme rarity of autoimmune disorders among sub-Saharan black Africans as long as they followed their traditional quasi-vegan lifestyles, and with recent ecologic studies correlating risks for IDDM and for multiple sclerosis mortality with animal product and/or saturated fat consumption. Moreover, there is evidence that vegan or quasi-vegan diets are useful in the management of rheumatoid arthritis, multiple sclerosis, and possibly SLE. The dopamine agonist bromocryptine exerts anti-inflammatory effects in rodent models of autoimmunity, and there is preliminary evidence that this drug may be clinically useful in several human autoimmune diseases; better tolerated D2-specific agonists such as cabergoline may prove to be more practical for use in therapy. The moderate clinical utility of supplemental fish oil in rheumatoid arthritis and certain other autoimmune disorders is documented. It is not unlikely that extra-thymic anti-inflammatory effects contribute importantly to the clinical utility of vegan diets, bromocryptine, and fish oil in autoimmunity. The favorable impact of low latitude or high altitude on autoimmune risk may be mediated by superior vitamin D status, which is associated with decreased secretion of parathyroid hormone; there are theoretical grounds for suspecting that parathyroid hormone may inhibit apoptosis in thymocytes. Androgens appear to up-regulate thymocyte apoptosis, may be largely responsible for the relative protection from autoimmunity enjoyed by men, and merit further evaluation for the management of autoimmunity in women. It will probably prove more practical to prevent autoimmune disorders than to reverse them once established; a whole-food vegan diet, coupled with fish oil and vitamin D supplementation, may represent a practical strategy for achieving this prevention, while concurrently lowering risk for many other life-threatening 'Western' diseases. Copyright 2001 Harcourt Publishers Ltd.",
"title": "Upregulation of lymphocyte apoptosis as a strategy for preventing and treating autoimmune disorders: a role for whole-food vegan diets, fish oil an..."
},
{
"docid": "MED-2816",
"text": "Plants contain numerous polyphenols, which have been shown to reduce inflammation and hereby to increase resistance to disease. Examples of such polyphenols are isothiocyanates in cabbage and broccoli, epigallocatechin in green tee, capsaicin in chili peppers, chalones, rutin and naringenin in apples, resveratrol in red wine and fresh peanuts and curcumin/curcuminoids in turmeric. Most diseases are maintained by a sustained discreet but obvious increased systemic inflammation. Many studies suggest that the effect of treatment can be improved by a combination of restriction in intake of proinflammatory molecules such as advanced glycation end products (AGE), advanced lipoperoxidation end products (ALE), and rich supply of antiinflammatory molecules such as plant polyphenols. To the polyphenols with a bulk of experimental documentation belong the curcuminoid family and especially its main ingredient, curcumin. This review summarizes the present knowledge about these turmericderived ingredients, which have proven to be strong antioxidants and inhibitors of cyclooxigenase-2 (COX-2), lipoxygenase (LOX) and nuclear factor kappa B (NF-kappaB) but also AGE. A plethora of clinical effects are reported in various experimental diseases, but clinical studies in humans are few. It is suggested that supply of polyphenols and particularly curcuminoids might be value as complement to pharmaceutical treatment, but also prebiotic treatment, in conditions proven to be rather therapy-resistant such as Crohn's, long-stayed patients in intensive care units, but also in conditions such as cancer, liver cirrhosis, chronic renal disease, chronic obstructive lung disease, diabetes and Alzheimer's disease.",
"title": "Plant-derived health: the effects of turmeric and curcuminoids."
},
{
"docid": "MED-2780",
"text": "Spices, such as cinnamon, cloves, cardamom, garlic, ginger, cumin, coriander and turmeric are used all over the world as flavouring and colouring ingredients in Indian foods. Previous studies have shown that spices contain variable amounts of total oxalates but there are few reports of soluble oxalate contents. In this study, the total, soluble and insoluble oxalate contents of ten different spices commonly used in Indian cuisine were measured. Total oxalate content ranged from 194 (nutmeg) to 4,014 (green cardamom) mg/100 g DM, while the soluble oxalate contents ranged from 41 (nutmeg) to 3,977 (green cardamom) mg/100 g DM. Overall, the percentage of soluble oxalate content of the spices ranged from 4.7 to 99.1% of the total oxalate content which suggests that some spices present no risk to people liable to kidney stone formation, while other spices can supply significant amounts of soluble oxalates and therefore should be used in moderation.",
"title": "Total and soluble oxalate content of some Indian spices."
},
{
"docid": "MED-2800",
"text": "The management of osteoarthritis represents a real challenge. This complex and multi-factorial disease evolves over decades and requires not only the alleviation of symptoms, i.e. pain and joint function but also the preservation of articular structure without side effects. Nutraceuticals are good candidates for the management of OA due to their safety profile and potential efficacy. However, they are not part of the treatment guidelines and published recommendations. Curcumin is the yellow pigment isolated from the rhizomes of Curcuma longa, commonly known as turmeric. Curcumin is a highly pleiotropic molecule with an excellent safety profile. Strong molecular evidence has been published for its potency to target multiple inflammatory diseases. However, naturally occurring curcumin cannot achieve its optimum therapeutic outcomes due to its low solubility and poor bioavailability. Nevertheless, curcumin presents great potential for treating OA and has been categorized as having preclinical evidence of efficacy. This review aimed at gathering most of the available information to document the potential efficacy of curcumin based on the results obtained in in vitro models of cartilage and osteoarthritis and in other diseases.",
"title": "Curcumin: a new paradigm and therapeutic opportunity for the treatment of osteoarthritis: curcumin for osteoarthritis management"
},
{
"docid": "MED-2582",
"text": "Nonstarch polysaccharide (NSP) intake was measured in representative samples of 30 men aged 50-59 in 2 urban and 2 rural Scandinavian populations that exhibited a 3-4 fold difference in incidence of large bowel cancer. Intake was measured by chemical analysis of complete duplicate portions of all food eaten over one day by each individual. NSP intakes showed a rural-urban gradient, with 18.4 +/- 7.8 g/day in rural Finland and 18.0 +/- 6.4 g/day in rural Denmark versus 14.5 +/- 5.4 g/day in urban Finland and 13.2 +/- 4.8 g/day in urban Denmark. NSP intakes were also calculated (using food tables) from weighed food records kept over 4 days, one of which was the day on which the duplicate collection was made. Intakes were 2-2.5 g/day higher with this method than with direct chemical analysis, mainly because published tables of values have become outdated and inaccurate as a result of improved methods for measuring NSP in food. Individual variation from day to day in NSP intake was considerable. Average NSP intake and intake of some of its component sugars were inversely related to colon cancer incidence in this geographical comparison. To show a relationship at the individual level between diet and cancer risk in a prospective study would require detailed and accurate methods for the assessment of NSP consumption.",
"title": "Nonstarch polysaccharide consumption in four Scandinavian populations."
},
{
"docid": "MED-2782",
"text": "BACKGROUND & AIMS: Curcumin is a biologically active phytochemical substance present in turmeric and has pharmacologic actions that might benefit patients with ulcerative colitis (UC). The aim in this trial was to assess the efficacy of curcumin as maintenance therapy in patients with quiescent ulcerative colitis (UC). METHODS: Eighty-nine patients with quiescent UC were recruited for this randomized, double-blind, multicenter trial of curcumin in the prevention of relapse. Forty-five patients received curcumin, 1g after breakfast and 1g after the evening meal, plus sulfasalazine (SZ) or mesalamine, and 44 patients received placebo plus SZ or mesalamine for 6 months. Clinical activity index (CAI) and endoscopic index (EI) were determined at entry, every 2 months (CAI), at the conclusion of 6-month trial, and at the end of 6-month follow-up. RESULTS: Seven patients were protocol violators. Of 43 patients who received curcumin, 2 relapsed during 6 months of therapy (4.65%), whereas 8 of 39 patients (20.51%) in the placebo group relapsed (P=.040). Recurrence rates evaluated on the basis of intention to treat showed significant difference between curcumin and placebo (P=.049). Furthermore, curcumin improved both CAI (P=.038) and EI (P=.0001), thus suppressing the morbidity associated with UC. A 6-month follow-up was done during which patients in both groups were on SZ or mesalamine. Eight additional patients in the curcumin group and 6 patients in the placebo group relapsed. CONCLUSIONS: Curcumin seems to be a promising and safe medication for maintaining remission in patients with quiescent UC. Further studies on curcumin should strengthen our findings.",
"title": "Curcumin maintenance therapy for ulcerative colitis: randomized, multicenter, double-blind, placebo-controlled trial."
},
{
"docid": "MED-2785",
"text": "Curcumin is extensively used as a spice and pigment and has anticarcinogenic effects that could be linked to its antioxidant properties. However, some studies suggest that this natural compound possesses both pro- and antioxidative effects. In this study, we found that curcumin induced DNA damage to both the mitochondrial and nuclear genomes in human hepatoma G2 cells. Using quantitative polymerase chain reaction and immunocytochemistry staining of 8-hydroxydeoxyguanosine, we demonstrated that curcumin induced dose-dependent damage in both the mitochondrial and nuclear genomes and that the mitochondrial damage was more extensive. Nuclear DNA fragments were also evident in comet assays. The mechanism underlies the elevated level of reactive oxygen species and lipid peroxidation generated by curcumin. The lack of DNA damage at low doses suggested that low levels of curcumin does not induce DNA damage and may play an antioxidant role in carcinogenesis. But at high doses, we found that curcumin imposed oxidative stress and damaged DNA. These data reinforce the hypothesis that curcumin plays a conflicting dual role in carcinogenesis. Also, the extensive mitochondrial DNA damage might be an initial event triggering curcumin-induced cell death.",
"title": "Mitochondrial and nuclear DNA damage induced by curcumin in human hepatoma G2 cells."
},
{
"docid": "MED-2559",
"text": "Inositol hexaphosphate (IP6) has anti-cancer properties, but recently other extracellular functions have been observed for IP6, including enhancing superoxide production and phagocytosis by neutrophils in the presence of microbial stimuli. This study investigated other inflammatory functions of IP6 on adherent neutrophils. The effect of IP6 on the release of IL-8, tumour necrosis factor (TNF-alpha) and IL-6 by neutrophils attached to either plastic or laminin for up to 6 hours in response to stimulation with lipopolysaccharide or N-formyl-Met-Leu-Phe (fMLP) was investigated. An increase in IL-8 secretion by stimulated cells occurred in the presence of IP6. The incubation of cells attached to laminin with IP6 alone (100-250 BM) did not effect cell morphology, but in the presence of 10(-7) M fMLP altered cell shape. A direct effect of IP6 on cell function was to trigger a sustained assembly of F-actin. Thus, exposure of neutrophils to low levels of IP6 appears to modulate selective neutrophil functions.",
"title": "Effect of IP6 on human neutrophil cytokine production and cell morphology."
},
{
"docid": "MED-2568",
"text": "Inositol hexaphosphate (InsP6 or IP6) is ubiquitous. At 10 microM to 1 mM concentrations, IP6 and its lower phosphorylated forms (IP(1-5)) as well as inositol (Ins) are contained in most mammalian cells, wherein they are important in regulating vital cellular functions such as signal transduction, cell proliferation and differentiation. A striking anti-cancer action of IP6 has been demonstrated both in vivo and in vitro, which is based on the hypotheses that exogenously administered IP6 may be internalized, dephosphorylated to IP(1-5), and inhibit cell growth. There is additional evidence that Ins alone may further enhance the anti-cancer effect of IP6. Besides decreasing cellular proliferation, IP6 also causes differentiation of malignant cells often resulting in a reversion to normal phenotype. These data strongly point towards the involvement of signal transduction pathways, cell cycle regulatory genes, differentiation genes, oncogenes and perhaps, tumor suppressor genes in bringing about the observed anti-neoplastic action of IP6.",
"title": "IP6: a novel anti-cancer agent."
},
{
"docid": "MED-2575",
"text": "Introduction Matrix metalloproteinases (MMPs) have repeatedly been shown to play a very active role in extracellular matrix degradation associated with tumor invasion and metastasis. Tissue inhibitors of MMPs (TIMPs) are well-known for their ability to inhibit MMP activity thereby inhibiting malignant progression. Inositol hexaphosphate (IP6 phytic acid) has been recognized to have both preventive and therapeutic effects against various cancers including that of colon. In in vitro studies, IP6 has been demonstrated to inhibit cancer cell adhesion and migration. In the present study, the effect of IP6 on the expression of MMP and TIMP genes was evaluated in unstimulated and IL-1β-stimulated colon cancer cell line Caco-2. Materials and methods Real-time QRT-PCR was used to validate the transcription level of selected MMP and TIMP genes in Caco-2 cells after treatment with 1 ng/ml of IL-1β, 2.5 mM of IP6, and both for 6, 12, and 24 h. Results Stimulation of cells with IL-1β only resulted in an overexpression of MMP and their TIMP mRNAs. A significant decrease in MMP-13, MMP-3, MMP-2, and TIMP-1 basal expression was achieved by IP6. IP6 was also an efficient downregulator of MMP-1, MMP-9, and TIMP-2 genes transcription stimulated by IL-1β in 6 h lasting culture. After 12 h, IL-1β-induced MMP-2 mRNA expression was significantly reduced by IP6. Conclusion Proinflammatory cytokine IL-1β upregulates MMP and TIMP mRNAs expression in colon cancer epithelial cells Caco-2. IP6 (2.5 mM) influences constitutive expression of both MMP and TIMP genes and downregulates IL-1β stimulated transcription of some of these genes. IP6 exerts its anti-metastatic activity through modulation of MMP and TIMP genes expression to prevent cancer cell migration and invasion.",
"title": "The effect of inositol hexaphosphate on the expression of selected metalloproteinases and their tissue inhibitors in IL-1β-stimulated colon cancer cells"
},
{
"docid": "MED-2791",
"text": "Curcumin, a polyphenolic compound derived from dietary spice turmeric, possesses diverse pharmacologic effects including anti-inflammatory, antioxidant, antiproliferative and antiangiogenic activities. Phase I clinical trials have shown that curcumin is safe even at high doses (12 g/day) in humans but exhibit poor bioavailability. Major reasons contributing to the low plasma and tissue levels of curcumin appear to be due to poor absorption, rapid metabolism, and rapid systemic elimination. To improve the bioavailability of curcumin, numerous approaches have been undertaken. These approaches involve, first, the use of adjuvant like piperine that interferes with glucuronidation; second, the use of liposomal curcumin; third, curcumin nanoparticles; fourth, the use of curcumin phospholipid complex; and fifth, the use of structural analogues of curcumin (e.g., EF-24). The latter has been reported to have a rapid absorption with a peak plasma half-life. Despite the lower bioavailability, therapeutic efficacy of curcumin against various human diseases, including cancer, cardiovascular diseases, diabetes, arthritis, neurological diseases and Crohn's disease, has been documented. Enhanced bioavailability of curcumin in the near future is likely to bring this promising natural product to the forefront of therapeutic agents for treatment of human disease.",
"title": "Bioavailability of curcumin: problems and promises."
},
{
"docid": "MED-2807",
"text": "In a previous three-month study of Meriva, a proprietary curcumin-phosphatidylcholine phytosome complex, decreased joint pain and improvement in joint function were observed in 50 osteoarthritis (OA) patients. Since OA is a chronic condition requiring prolonged treatment, the long-term efficacy and safety of Meriva were investigated in a longer (eight months) study involving 100 OA patients. The clinical end points (Western Ontario and McMaster Universities [WOMAC] score, Karnofsky Performance Scale Index, and treadmill walking performance) were complemented by the evaluation of a series of inflammatory markers (interleukin [IL]-1beta, IL-6, soluble CD40 ligand [sCD40L], soluble vascular cell adhesion molecule (sVCAM)-1, and erythrocyte sedimentation rate [ESR]). This represents the most ambitious attempt, to date, to evaluate the clinical efficacy and safety of curcumin as an anti-inflammatory agent. Significant improvements of both the clinical and biochemical end points were observed for Meriva compared to the control group. This, coupled with an excellent tolerability, suggests that Meriva is worth considering for the long-term complementary management of osteoarthritis.",
"title": "Efficacy and safety of Meriva®, a curcumin-phosphatidylcholine complex, during extended administration in osteoarthritis patients."
},
{
"docid": "MED-2578",
"text": "The incidence of colonic cancer differs widely between various human populations. It has been suggested that dietary fiber content is of utmost importance and is inversely related to the occurrence of colonic cancer. However, high-fiber diets are not always correlated with low frequency of colonic cancer, suggesting the involvement of additional dietary constituents. Inositol hexaphosphate (phytic acid) is an abundant plant seed component present in many, but not all, fiber-rich diets. The authors have found that phytic acid is a potent inhibitor of iron-mediated generation of the hazardous oxidant, hydroxyl radical. Herein, the authors propose that inhibition of intracolonic hydroxyl radical generation, via the chelation of reactive iron by phytic acid, may help explain the suppression of colonic carcinogenesis and other inflammatory bowel diseases by diets rich in phytic acid.",
"title": "Dietary suppression of colonic cancer. Fiber or phytate?"
},
{
"docid": "MED-2804",
"text": "Osteoarthritis (OA) is the most common form of arthritis in the US, and a leading cause of disability. It is typically defined in epidemiologic studies on the basis of radiographic findings and consideration of symptoms. Its incidence and prevalence are rising, likely related to the aging of the population and increasing obesity. Risk factors for OA include a number of person-level factors, such as age, sex, obesity, and genetics, as well as joint-specific factors that are likely reflective of abnormal loading of the joints. A number of methodologic challenges exist in studying OA that can hamper our ability to identify pertinent relationships.",
"title": "Epidemiology of OA"
},
{
"docid": "MED-2797",
"text": "Osteoarthritis (OA) has long been considered a \"wear and tear\" disease leading to loss of cartilage. OA used to be considered the sole consequence of any process leading to increased pressure on one particular joint or fragility of cartilage matrix. Progress in molecular biology in the 1990s has profoundly modified this paradigm. The discovery that many soluble mediators such as cytokines or prostaglandins can increase the production of matrix metalloproteinases by chondrocytes led to the first steps of an \"inflammatory\" theory. However, it took a decade before synovitis was accepted as a critical feature of OA, and some studies are now opening the way to consider the condition a driver of the OA process. Recent experimental data have shown that subchondral bone may have a substantial role in the OA process, as a mechanical damper, as well as a source of inflammatory mediators implicated in the OA pain process and in the degradation of the deep layer of cartilage. Thus, initially considered cartilage driven, OA is a much more complex disease with inflammatory mediators released by cartilage, bone and synovium. Low-grade inflammation induced by the metabolic syndrome, innate immunity and inflammaging are some of the more recent arguments in favor of the inflammatory theory of OA and highlighted in this review. Copyright © 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.",
"title": "Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!)."
},
{
"docid": "MED-2788",
"text": "Turmeric root has been used medicinally in China and India for thousands of years. The active components are thought to be the curcuminoids, primarily curcumin, which is commonly available worldwide as a standardized extract. This article reviews the pharmacology of curcuminoids, their use and efficacy, potential adverse effects, and dosage and standardization. Preclinical studies point to mechanisms of action that are predominantly anti-inflammatory and antineoplastic, while early human clinical trials suggest beneficial effects for dyspepsia, peptic ulcer, inflammatory bowel disease, rheumatoid arthritis, osteoarthritis, uveitis, orbital pseudotumor, and pancreatic cancer. Curcumin is well-tolerated; the most common side effects are nausea and diarrhea. Theoretical interactions exist due to purported effects on metabolic enzymes and transport proteins, but clinical reports do not support any meaningful interactions. Nonetheless, caution, especially with chemotherapy agents, is advised. Late-phase clinical trials are still needed to confirm most beneficial effects.",
"title": "Clinical utility of curcumin extract."
},
{
"docid": "MED-2602",
"text": "In this study, we investigated the molecular pathways targeted by curcumin during apoptosis of human melanoma cell lines. We found that curcumin caused cell death in eight melanoma cell lines, four with wild-type and four with mutant p53. We demonstrate that curcumin-induced apoptosis is both dose- and time-dependent. We found that curcumin did not induce p53, suggesting that curcumin activates other apoptosis pathways. Our data show that curcumin activates caspases-3 and -8 but not caspase-9, supporting the rationale that apoptosis occurs via a membrane-mediated mechanism. Both a caspase-8 and broad-based caspase inhibitor, but not a caspase-9 specific inhibitor, suppressed curcumin-induced cell death. To further support our hypothesis that curcumin induces activation of a death receptor pathway, we show that curcumin induces Fas receptor aggregation in a FasL-independent manner and that low-temperature incubation, previously shown to inhibit receptor aggregation, prevented curcumin-induced cell death. Moreover, we demonstrate that expression of dominant negative FADD significantly inhibited curcumin-induced cell death. In addition, our results indicate that curcumin also blocks the NF-kappaB cell survival pathway and suppresses the apoptotic inhibitor, XIAP. Since melanoma cells with mutant p53 are strongly resistant to conventional chemotherapy, curcumin may overcome the chemoresistance of these cells and provide potential new avenues for treatment.",
"title": "Curcumin induces apoptosis in human melanoma cells through a Fas receptor/caspase-8 pathway independent of p53."
},
{
"docid": "MED-5341",
"text": "The present study investigated the effects of a diet and exercise intervention on known breast cancer (BCa) risk factors, including estrogen, obesity, insulin, and insulin-like growth factor-I (IGF-I), in overweight/obese, postmenopausal women. In addition, using the subjects' pre- and postintervention serum in vitro, serum-stimulated growth and apoptosis of three estrogen receptor-positive BCa cell lines were studied. The women where placed on a low-fat (10-15% kcal), high-fiber (30-40 g per 1,000 kcal/day) diet and attended daily exercise classes for 2 wk. Serum estradiol was reduced in the women on hormone treatment (HT; n = 28) as well as those not on HT (n = 10). Serum insulin and IGF-I were significantly reduced in all women, whereas IGF binding protein-1 was increased significantly. In vitro growth of the BCa cell lines was reduced by 6.6% for the MCF-7 cells, 9.9% for the ZR-75-1 cells, and 18.5% for the T-47D cells. Apoptosis was increased by 20% in the ZR-75-1 cells, 23% in the MCF-7 cells, and 30% in the T-47D cells (n = 12). These results show that a very-low-fat, high-fiber diet combined with daily exercise results in major reductions in risk factors for BCa while subjects remained overweight/obese. These in vivo serum changes slowed the growth and induced apoptosis in serum-stimulated BCa cell lines in vitro.",
"title": "Effects of a low-fat, high-fiber diet and exercise program on breast cancer risk factors in vivo and tumor cell growth and apoptosis in vitro."
},
{
"docid": "MED-2579",
"text": "There are now extensive scientific data suggesting the potential role of dietary and non-dietary phytochemicals in the prevention and control of prostate cancer (PCA) growth and progression. PCA is a disease of elderly male populations with a relatively slower rate of growth and progression as compared to most other cancers and, therefore, is a candidate disease for preventive intervention. Overall, PCA growth and progression involve aberrant mitogenic and survival signaling and deregulated cell cycle progression, accompanied by gradual accumulation of genetic and epigenetic changes over a period of years. Several mechanisms, including overexpression of growth, survival and angiogenic factors and their receptors, together with a loss/decrease of tumor suppressor p53, retinoblastoma and cyclin-dependent kinase inhibitor, have been implicated in PCA growth and progression. Therefore, phytochemicals targeting these molecular events could have a promising role in PCA prevention and/or therapy. Inositol hexaphosphate (IP6) is a major constituent of most cereals, legumes, nuts, oil seeds and soybean. Taken orally as an over-the-counter dietary/nutrient supplement, and is recognised as offering several health benefits without any known toxicity. In vitro anticancer efficacy of IP6 has been observed in many human, mouse and rat prostate cancer cells. Completed studies also show that oral feeding of IP6 inhibits human PCA xenograft growth in nude mice without toxicity. In a recently completed pilot study, we observed similar preventive effects of IP6 on prostate tumorigenesis in the TRAMP model. Mechanistic studies indicate that IP6 targets mitogenic and survival signaling, as well as cell cycle progression, in PCA cells. IP6 is also shown to target molecular events associated with angiogenesis. Moreover, IP6 has pleiotropic molecular targets for its overall efficacy against PCA and, therefore, could be a suitable candidate agent for preventive intervention of this malignancy in humans.",
"title": "Prostate cancer and inositol hexaphosphate: efficacy and mechanisms."
},
{
"docid": "MED-2570",
"text": "The functional properties, including antioxidant and chemopreventative capacities as well as the inhibitory effects on angiotensin-converting enzyme (ACE), α-glucosidase and pancreatic lipase, of three Australian-grown faba bean genotypes (Nura, Rossa and TF(Ic*As)*483/13) were investigated using an array of in vitro assays. Chromatograms of on-line post column derivatisation assay coupled with HPLC revealed the existence of active phenolics (hump) in the coloured genotypes, which was lacking in the white-coloured breeding line, TF(Ic*As)*483/13. Roasting reduced the phenolic content, and diminished antioxidant activity by 10-40 % as measured by the reagent-based assays (diphenylpicrylhydrazyl, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) and oxygen radical absorbance capacity) in all genotypes. Cell culture-based antioxidant activity assay (cellular antioxidant activity) showed an increase of activity in the coloured genotypes after roasting. Faba bean extracts demonstrated cellular protection ability against H₂O₂-induced DNA damage (assessed using RAW264.7 cells), and inhibited the proliferation of all human cancer cell lines (BL13, AGS, Hep G2 and HT-29) evaluated. However, the effect of faba bean extracts on the non-transformed human cells (CCD-18Co) was negligible. Flow cytometric analyses showed that faba bean extracts successfully induced apoptosis of HL-60 (acute promyelocytic leukaemia) cells. The faba bean extracts also exhibited ACE, α-glucosidase and pancreatic lipase inhibitory activities. Overall, extracts from Nura (buff-coloured) and Rossa (red-coloured) were comparable, while TF(Ic*As)*483/13 (white-coloured) contained the lowest phenolic content and exhibited the least antioxidant and enzyme inhibition activities. These results are important to promote the utilisation of faba beans in human diets for various health benefits.",
"title": "In vitro investigations of the potential health benefits of Australian-grown faba beans (Vicia faba L.): chemopreventative capacity and inhibitory ..."
},
{
"docid": "MED-2817",
"text": "Curcumin (diferuloylmethane), a yellow coloring agent extracted from turmeric is also used as a remedy for the treatment and prevention of inflammatory diseases. Acute and chronic inflammation is a major factor in the progression of obesity, type II diabetes, arthritis, pancreatitis, cardiovascular, neurodegenerative and metabolic diseases, as well as certain types of cancer. Turmeric has a long history of use in Ayurvedic medicine for the treatment of inflammatory disorders. Recent studies on the efficacy and therapeutic applicability of turmeric have suggested that the active ingredient of tumeric is curcumin. Further, compelling evidence has shown that curcumin has the ability to inhibit inflammatory cell proliferation, invasion, and angiogenesis through multiple molecular targets and mechanisms of action. Curcumin is safe, non-toxic, and mediates its anti-inflammatory effects through the down-regulation of inflammatory transcription factors, cytokines, redox status, protein kinases, and enzymes that all promote inflammation. In addition, curcumin induces apoptosis through mitochondrial and receptor-mediated pathways, as well as activation of caspase cascades. In the current study, the anti-inflammatory effects of curcumin were evaluated relative to various chronic inflammatory diseases. Based on the available pharmacological data obtained from in vitro and in vivo research, as well as clinical trials, an opportunity exists to translate curcumin into clinics for the prevention of inflammatory diseases in the near future. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.",
"title": "Curcumin in inflammatory diseases."
},
{
"docid": "MED-4113",
"text": "Clonal deletion is arguably the most important mechanism of eliminating self-reactive thymocytes from the T-cell repertoire. Recent work has identified new players in this process. On the thymocyte side, several molecules have been newly implicated in the pathway from initial T-cell receptor signaling through to the final result: gene transcription and thymocyte apoptosis. In addition, several proapoptotic molecules have been found to be necessary for the death of self-reactive thymocytes. On the antigen-presenting cell side, the expression of peripheral self-antigens, regulated at least in part by the autoimmune regulator (AIRE) protein, is crucial for complete elimination of autoreactive thymocytes. The importance of thymic peripheral antigen expression and clonal deletion to self-tolerance is demonstrated in the autoimmune diseases autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy and type-1 diabetes mellitus.",
"title": "Good riddance: Thymocyte clonal deletion prevents autoimmunity."
},
{
"docid": "MED-2598",
"text": "Death receptors belong to the TNF receptor family and are characterised by an intracellular death domain that serves to recruit adapter proteins such as TRADD and FADD and cysteine proteases such as Caspase-8. Activation of Caspase-8 on the aggregated receptor leads to apoptosis. Triggering of death receptors is mediated through the binding of specific ligands of the TNF family, which are homotrimeric type-2 membrane proteins displaying three receptor binding sites. There are various means of modulating the activation of death receptors. The status of the ligand (membrane-bound vs. soluble) is critical in the activation of Fas and of TRAIL receptors. Cleavage of membrane-bound FasL to a soluble form (sFasL) does not affect its ability to bind to Fas but drastically decreases its cytotoxic activity. Conversely, cross-linking epitope-tagged sFasL with anti-tag antibodies to mimic membrane-bound ligand results in a 1000-fold increase in cytotoxicity. This suggests that more than three Fas molecules need to be aggregated to efficiently signal apoptosis. Death receptors can also be regulated by decoy receptors. The cytotoxic ligand TRAIL interacts with five receptors, only two of which (TRAIL-R1 and -R2) have a death domain. TRAIL-R3 is anchored to the membrane by a glycolipid and acts as a dominant negative inhibitor of TRAIL-mediated apoptosis when overexpressed on TRAIL-sensitive cells. Intracellular proteins interacting with the apoptotic pathway are potential modulators of death receptors. FLIP resembles Caspase-8 in structure but lacks protease activity. It interacts with both FADD and Caspase-8 to inhibits the apoptotic signal of death receptors and, at the same time, can activate other signalling pathways such as that leading to NF-kappa B activation.",
"title": "Apoptosis induced by death receptors."
},
{
"docid": "MED-2803",
"text": "Osteoarthritis is a condition caused in part by injury, loss of cartilage structure and function, and an imbalance in inflammatory and anti-inflammatory pathways. It primarily affects the articular cartilage and subchondral bone of synovial joints and results in joint failure, leading to pain upon weight bearing including walking and standing. There is no cure for osteoarthritis, as it is very difficult to restore the cartilage once it is destroyed. The goals of treatment are to relieve pain, maintain or improve joint mobility, increase the strength of the joints and minimize the disabling effects of the disease. Recent studies have shown an association between dietary polyphenols and the prevention of osteoarthritis-related musculoskeletal inflammation. This review discusses the effects of commonly consumed polyphenols, including curcumin, epigallocatechin gallate and green tea extract, resveratrol, nobiletin and citrus fruits, pomegranate, as well as genistein and soy protein, on osteoarthritis with an emphasis on molecular antiosteoarthritic mechanisms. Copyright © 2012 Elsevier Inc. All rights reserved.",
"title": "Dietary polyphenols and mechanisms of osteoarthritis."
},
{
"docid": "MED-2830",
"text": "OBJECTIVE: The aim of this work was to determine the bioavailability of herbs and spices after human consumption by measuring the ability to protect lymphocytes from an oxidative injury and by examining the impact on inflammatory biomarkers in activated THP-1 cells. METHODS: Ten to 12 subjects in each of 13 groups consumed a defined amount of herb or spice for 7 days. Blood was drawn from subjects before consumption and 1 hour after taking the final herb or spice capsules. Subject serum and various extractions of the herbs and spices were analyzed for antioxidant capacity by oxygen radical absorbance capacity (ORAC) analysis or by 1,1-diphenyl-2-picrylhydrzyl (DPPH). Subject peripheral blood mononuclear cells (PBMCs) in medium with10% autologous serum were incubated with hydrogen peroxide to induce DNA strand breaks. Subject serum was also used to treat activated THP-1 cells to determine relative quantities of 3 inflammatory cytokine (tumor necrosis factor-α [TNF-α], interleukin-1α [IL-1α], and IL-6) mRNAs. RESULTS: Herbs and spices that protected PBMCs against DNA strand breaks were paprika, rosemary, ginger, heat-treated turmeric, sage, and cumin. Paprika also appeared to protect cells from normal apoptotic processes. Of the 3 cytokine mRNAs studied (TNF-α, IL-1α, and IL-6), TNF-α was the most sensitive responder to oxidized LDL-treated macrophages. Clove, ginger, rosemary, and turmeric were able to significantly reduce oxidized LDL-induced expression of TNF-α. Serum from those consuming ginger reduced all three inflammatory biomarkers. Ginger, rosemary, and turmeric showed protective capacity by both oxidative protection and inflammation measures. CONCLUSIONS: DNA strand breaks and inflammatory biomarkers are a good functional measure of a food's bioavailability.",
"title": "Bioavailability of herbs and spices in humans as determined by ex vivo inflammatory suppression and DNA strand breaks."
},
{
"docid": "MED-4319",
"text": "The article gives an overview of phytic acid in food and of its significance for human nutrition. It summarises phytate sources in foods and discusses problems of phytic acid/phytate contents of food tables. Data on phytic acid intake are evaluated and daily phytic acid intake depending on food habits is assessed. Degradation of phytate during gastro-intestinal passage is summarised, the mechanism of phytate interacting with minerals and trace elements in the gastro-intestinal chyme described and the pathway of inositol phosphate hydrolysis in the gut presented. The present knowledge of phytate absorption is summarised and discussed. Effects of phytate on mineral and trace element bioavailability are reported and phytate degradation during processing and storage is described. Beneficial activities of dietary phytate such as its effects on calcification and kidney stone formation and on lowering blood glucose and lipids are reported. The antioxidative property of phytic acid and its potentional anticancerogenic activities are briefly surveyed. Development of the analysis of phytic acid and other inositol phosphates is described, problems of inositol phosphate determination and detection discussed and the need for standardisation of phytic acid analysis in foods argued.",
"title": "Phytate in foods and significance for humans: food sources, intake, processing, bioavailability, protective role and analysis."
},
{
"docid": "MED-2821",
"text": "The purpose of this review is to summarize the pertinent literature published in the present era regarding the antiulcerogenic property of curcumin against the pathological changes in response to ulcer effectors (Helicobacter pylori infection, chronic ingestion of non-steroidal anti-inflammatory drugs, and exogenous substances). The gastrointestinal problems caused by different etiologies was observed to be associated with the alterations of various physiologic parameters such as reactive oxygen species, nitric oxide synthase, lipid peroxidation, and secretion of excessive gastric acid. Gastrointestinal ulcer results probably due to imbalance between the aggressive and the defensive factors. In 80% of the cases, gastric ulcer is caused primarily due to the use of non-steroidal anti-inflammatory category of drug, 10% by H. pylori, and about 8-10% by the intake of very spicy and fast food. Although a number of antiulcer drugs and cytoprotectants are available, all these drugs have side effects and limitations. In the recent years a widespread search has been launched to identify new antiulcer drugs from synthetic and natural resources. An Indian dietary derivative (curcumin), a yellow pigment found in the rhizome of Curcuma longa, has been widely used for the treatment of several diseases. Epidemiologically, it was suggested that curcumin might reduce the risk of inflammatory disorders, such as cancer and ulcer. These biological effects are attributed to its anti-inflammatory and antioxidant activities. It can, therefore, be reported from the literature that curcumin PRevents gastrointestinal-induced ulcer and can be recommended as a novel drug for ulcer treatment.",
"title": "Turmeric (curcumin) remedies gastroprotective action"
},
{
"docid": "MED-4112",
"text": "Co-stimulatory signals through the CD28 receptor enhance the survival of T cells that have their antigen receptor (TCR) engaged. Here we show that stimulation through the CD28 receptor in the absence of TCR engagement with either an anti-CD28 cross-linking antibody or the CD80 ligand transiently increases expression of the insulin-like growth factor-I receptor (IGF-IR) on T cells. Antibodies that block signaling through the IGF-IR decrease the survival of T cells activated through the TCR and CD28 in the presence of IL-2 by more than 50%, and also enhance susceptibility to Fas-induced apoptosis. CD28 stimulation increases IGF-IR expression on Jurkat cells, and exogenously added IGF-I can protect these cells from Fas-induced apoptosis. We conclude that CD28-mediated enhancement of IGF-IR expression provides activated T cells with essential survival signals that are independent of survival mediated by IL-2 and Bcl-xl.",
"title": "The insulin-like growth factor-I receptor is regulated by CD28 and protects activated T cells from apoptosis."
},
{
"docid": "MED-2581",
"text": "A hospital-based case-control study of diet and colorectal cancer was conducted among Chinese in Singapore (who constitute 77% of the population). A total of 203 cases and 425 controls were included. A history of the usual dietary intake one year prior to interview was taken using a quantitative food frequency questionnaire. Daily intakes of nutrients and selected food items were computed and stratified by tertiles of the control range, to assess risk in low-, medium- and high-intake categories. Effects were adjusted in analysis for age, sex, Chinese dialect group and occupation. For cancers of colon and rectum combined, significant observations were a protective effect of high cruciferous vegetable intake (OR = 0.50, p less than 0.01) and a predisposing effect of a high meat/vegetable consumption ratio (OR = 1.77, p less than 0.05). Similar results were observed for colon cancer alone. For rectal cancer alone (only 71 cases), significant (p less than 0.05) protective effects were observed for high intakes of protein (OR = 0.61), fibre (OR = 0.46), beta-carotene (OR = 0.54), cruciferous vegetables (OR = 0.51) and total vegetables (OR = 0.51). When further assessed by multiple logistic regression, tests for trend and assessment of risk in the extreme highest and lowest quintiles of the control range, the factors consistently significant were cruciferous vegetable intake and the meat/vegetable ratio. A particularly high relative risk was also noted in association with low coffee consumption (OR = 1.59, with p less than 0.05 for trend). No consistent trends were noted for fat or fibre intakes. For non-dietary variables investigated, a history of cholecystectomy increased the risk of both cancers combined (OR = 3.43, p less than 0.05) and colon cancer alone (OR = 4.39, p less than 0.01). This study in an Asian population of countries of Southern and Eastern Asia newly undergoing industrialization and in which rapid economic change is reflected in changing cancer patterns, suggests that the protective effects of certain dietary constituents, notably the cruciferous vegetables, may be more important than the hitherto stressed carcinogenic potential of fat and protein.",
"title": "Colorectal cancer and diet in an Asian population--a case-control study among Singapore Chinese."
},
{
"docid": "MED-2603",
"text": "FAS-associated protein with death domain (FADD) is the key adaptor protein transmitting apoptotic signals mediated by the main death receptors (DRs). Besides being an essential instrument in cell death, FADD is also implicated in proliferation, cell cycle progression, tumor development, inflammation, innate immunity, and autophagy. Recently, many of these new functions of FADD were shown to be independent of DRs. Moreover, FADD function is dictated by protein localization and phosphorylation state. Thus, FADD is a crucial and unique controller of many essential cellular processes. The full understanding of the networks dictating the ultimate function of FADD may provide a new paradigm for other multifaceted proteins. Copyright 2010 Elsevier Ltd. All rights reserved.",
"title": "FADD: a regulator of life and death."
},
{
"docid": "MED-2808",
"text": "Chemotherapy remains the core of anticancer treatment. However, despite the tremendous strides made in the development of targeted anticancer therapies, emergence of resistance to chemotherapeutic drugs is still a major obstacle in the successful management of resistant tumours. Therefore, profound investigation into the in-depth molecular mechanisms of drug resistance is essential and may hopefully translate into effective therapies that can flip the switch from drug resistance to susceptibility. Mechanistically, resistance phenomena may be explained by (i) overexpression of drug efflux pumps, (ii) enhanced drug detoxification, (iii) rapid DNA repair efficiency, (iv) defects in apoptosis regulation, and (v) active cell survival signals. Several adverse effects associated with multidrug resistance and the need for safe multi-targeted anticancer drugs instigated the use of the phytochemical, curcumin, the yellow pigment of the spice turmeric, which has pleotropic activities. We performed a structured literature review using PubMed and Medline searches with secondary review of cited publications, identifying studies on the role of curcumin in conquering drug resistance in cancer. This review describes how curcumin sensitizes cancer cells through regulation of multiple multidrug resistance pathways, thus employing one drug for multiple targets. Curcumin helps the cancer cells to regain their 'forgotten' apoptosis, modulates drug-target interaction at different levels, restrains survival pathways when their proteins are overexpressed, and finds an alternate way to carry forward the process of sensitization of different resistant tumours. Additionally, the review dissects the role of curcumin, if any, in targeting the major culprit of drug resistance, cancer stem cells (CSC), thereby circumventing resistance. Taken together, this review strongly suggests that curcumin is a promising chemosensitizing agent and that the unique properties of curcumin may be exploited for successful management of resistant tumours.",
"title": "Death by design: where curcumin sensitizes drug-resistant tumours."
},
{
"docid": "MED-4115",
"text": "Cui and associates show that healthy individuals have natural autoantibodies (NAAs) specific for myeloperoxidase, proteinase 3, and glomerular basement membrane (GBM) with the same specificity as anti-neutrophil cytoplasmic antibodies and anti-GBM antibodies that are pathogenic. Although Ehrlich proposed horror autotoxicus and Burnet envisioned elimination of forbidden clones, NAAs are present in all healthy individuals and play beneficial homeostatic roles. Pathogenic autoimmunity is dysregulation of natural homeostatic autoimmunity rather than onset of a previously absent self-recognition.",
"title": "The rise and fall of horror autotoxicus and forbidden clones."
},
{
"docid": "MED-2580",
"text": "Adequate fruit and vegetable intake was suggested to protect against colorectal cancer and colorectal adenomas; however, several recent prospective studies reported no association. We examined the association between fruits and vegetables and adenomatous polyp recurrence in the Polyp Prevention Trial (PPT). The PPT was a low-fat, high-fiber, high-fruit, and vegetable dietary intervention trial of adenoma recurrence, in which there were no differences in the rate of adenoma recurrence in participants in the intervention and control arms of the trial. In this analysis of the entire PPT trial–based cohort, multiple logistic regression analysis was used to estimate the odds ratio (OR) of advanced and nonadvanced adenoma recurrence within quartiles of baseline and change (baseline minus the mean over 3 y) in fruit and vegetable intake, after adjustment for age, total energyy intake, use of nonsteroidal anti-inflammatory drugs, BMI, and gender. There were no significant associations between nonadvanced adenoma recurrence and overall change in fruit and vegetable consumption; however, those in the highest quartile of change in dry bean intake (greatest increase) compared with those in the lowest had a significantly reduced OR for advanced adenoma recurrence (OR = 0.35; 95% CI, 0.18–0.69; P for trend = 0.001). The median in the highest quartile of change in dry bean intake was 370% higher than the baseline intake. The PPT trial–based cohort provides evidence that dry beans may be inversely associated with advanced adenoma recurrence.",
"title": "High Dry Bean Intake and Reduced Risk of Advanced Colorectal Adenoma Recurrence among Participants in the Polyp Prevention Trial"
},
{
"docid": "MED-2823",
"text": "Curcumin, the yellow pigment from the rhizoma of Curcuma longa, is a widely studied phytochemical which has a variety of biological activities: anti-inflammatory and anti-oxidative. In this review we discuss the biological mechanisms and possible clinical effects of curcumin treatment on cancer therapy, and neurodegenerative diseases such as Alzheimer's Disease, with particular attention to the cell death processes induced by curcumin. Since oxidative stress and inflammation are major determinants of the aging process, we also argue that curcumin can have a more general effect that slows down the rate of aging. Finally, the effects of curcumin can be described as xenohormetic, since it activates a sort of stress response in mammalian cells.",
"title": "Curcumin in Cell Death Processes: A Challenge for CAM of Age-Related Pathologies"
},
{
"docid": "MED-2607",
"text": "Numerous natural compounds have been extensively investigated for their potential for cancer prevention over decades. Curcumin, from Curcuma longa, is a highly promising natural compound that can be potentially used for chemoprevention of multiple cancers. Curcumin modulates multiple molecular pathways involved in the lengthy carcinogenesis process to exert its chemopreventive effects through several mechanisms: promoting apoptosis, inhibiting survival signals, scavenging reactive oxidative species (ROS), and reducing the inflammatory cancer microenvironment. Curcumin fulfills the characteristics for an ideal chemopreventive agent with its low toxicity, affordability, and easy accessibility. Nevertheless, the clinical application of curcumin is currently compromised by its poor bioavailability. Here we review the potential of curcumin in cancer prevention, its molecular targets, and action mechanisms. Finally, we suggest specific recommendations to improve its efficacy and bioavailability for clinical applications.",
"title": "New perspectives of curcumin in cancer prevention"
},
{
"docid": "MED-2799",
"text": "Objective: To compare selected immunohistological features of inflammation in synovial tissue from patients with early and late osteoarthritis (OA). Methods: Synovial tissue samples were obtained from 10 patients with knee pain, normal radiographs, and arthroscopic manifestations of OA (early OA), and from 15 patients with OA undergoing knee joint arthroplasty (late OA). Conventional immunohistochemical techniques were used to measure microscopic manifestations of inflammation. The inflammatory cell infiltrate, blood vessel formation, and angiogenic factors, NF-κB activation, expression of tumour necrosis factor α (TNFα) and interleukin 1ß (IL1ß), and the presence of cyclo-oxygenase (COX)-1 and COX-2 were quantified. Fibroblast-like synoviocytes (FLS) were isolated from early and late OA tissue samples to compare in vitro production of prostaglandin E2 (PGE2) Results: Synovial tissue from patients with early OA demonstrated significantly greater CD4+ (p = 0.017) and CD68+ (p<0.001) cell infiltration, blood vessel formation (p = 0.01), vascular endothelial growth factor (p = 0.001), and intercellular adhesion molecule-1 expression (p<0.001). Numbers of cells producing TNFα and IL1ß were also significantly greater in early OA (p<0.001). Manifestations of inflammation in early OA were associated with increased expression of the NF-κB1 (p<0.001) and RelA (p = 0.015) subunits, and with increased COX-2 expression (p = 0.04). Cytokine-induced PGE2 production by cultured FLS was similar in both groups. Conclusion: Increased mononuclear cell infiltration and overexpression of mediators of inflammation were seen in early OA, compared with late OA. Isolated FLS were functionally similar in both groups, consistent with microenvironmental differences in the synovial tissue during different phases of OA. These observations may have important therapeutic implications for some patients during the early evolution of OA.",
"title": "Synovial tissue inflammation in early and late osteoarthritis"
},
{
"docid": "MED-2577",
"text": "A case-control study probing the role of diet on the incidence of colorectal cancer was undertaken in Athens, Greece, in a population characterized by ethnic homogeneity but substantial heterogeneity with respect to dietary habits. The case series consisted of 100 consecutive patients with histologically confirmed colorectal cancer admitted to two large hospitals of Athens during a 16-month period; the control series consisted of orthopaedic patients, admitted to the same hospitals during the same time period, individually matched to the index cases by age and sex. Dietary histories concerning the frequency of consumption (per month or per week) of about 80 food items were obtained by the same interviewer. Cases reported significantly less frequent consumption of vegetables (particularly beets, spinach, lettuce and cabbage) and, independently, significantly more frequent consumption of meat (notably lamb and beef). Between the two extremes (high-vegetable, low-meat diet versus high-meat, low-vegetable diet) a risk ratio of about 8 appears to exist, sufficient (in size and direction) to explain a substantial part of the international variation in the incidence of colorectal cancer. Significant associations were not found with beer or other alcoholic beverages, and significant interactions were not noted with respect to age, sex and anatomic localization (colon vs. rectum).",
"title": "Diet and colorectal cancer: a case-control study in Greece."
},
{
"docid": "MED-2571",
"text": "Background Prospective, randomized, pilot clinical study was conducted to evaluate the beneficial effects of inositol hexaphosphate (IP6) + Inositol in breast cancer patients treated with adjuvant therapy. Patients and methods Patients with invasive ductal breast cancer where polychemotherapy was indicated were monitored in the period from 2005-2007. Fourteen patients in the same stage of ductal invasive breast cancer were involved in the study, divided in two randomized groups. One group was subjected to take IP6 + Inositol while the other group was taking placebo. In both groups of patients the same laboratory parameters were monitored. When the treatment was finished, all patients have filled questionnaires QLQ C30 and QLQ-BR23 to determine the quality of life. Results Patients receiving chemotherapy, along with IP6 + Inositol did not have cytopenia, drop in leukocyte and platelet counts. Red blood cell counts and tumor markers were unaltered in both groups. However, patients who took IP6 + Inositol had significantly better quality of life (p = 0.05) and functional status (p = 0.0003) and were able to perform their daily activities. Conclusion IP6 + Inositol as an adjunctive therapy is valuable help in ameliorating the side effects and preserving quality of life among the patients treated with chemotherapy.",
"title": "Efficacy of IP6 + inositol in the treatment of breast cancer patients receiving chemotherapy: prospective, randomized, pilot clinical study"
},
{
"docid": "MED-2811",
"text": "Inflammatory bowel disease (IBD) comprising of ulcerative colitis (UC) and Crohn's disease (CD) is a major ailment affecting the small and large bowel. In clinics, IBD is treated using 5-amninosalicylates, antibiotics, the steroids and immunomodulators. Unfortunately, the long term usages of these agents are associated with undue side effects and compromise the therapeutic advantage. Accordingly, there is a need for novel agents that are effective, acceptable and non toxic to humans. Preclinical studies in experimental animals have shown that curcumin, an active principle of the Indian spice turmeric (Curcuma longa Linn) is effective in preventing or ameliorating UC and inflammation. Over the last few decades there has been increasing interest in the possible role of curcumin in IBD and several studies with various experimental models of IBD have shown it to be effective in mediating the inhibitory effects by scavenging free radicals, increasing antioxidants, influencing multiple signaling pathways, especially the kinases (MAPK, ERK), inhibiting myeloperoxidase, COX-1, COX-2, LOX, TNF-α, IFN-γ, iNOS; inhibiting the transcription factor NF-κB. Clinical studies have also shown that co-administration of curcumin with conventional drugs was effective, to be well-tolerated and treated as a safe medication for maintaining remission, to prevent relapse and improve clinical activity index. Large randomized controlled clinical investigations are required to fully understand the potential of oral curcumin for treating IBD.",
"title": "Curcumin, an active component of turmeric in the prevention and treatment of ulcerative colitis: preclinical and clinical observations."
},
{
"docid": "MED-2818",
"text": "Curcumin is a polyphenol derived from the herbal remedy and dietary spice turmeric. It possesses diverse anti-inflammatory and anti-cancer properties following oral or topical administration. Apart from curcumin's potent antioxidant capacity at neutral and acidic pH, its mechanisms of action include inhibition of several cell signalling pathways at multiple levels, effects on cellular enzymes such as cyclooxygenase and glutathione S-transferases, immuno-modulation and effects on angiogenesis and cell-cell adhesion. Curcumin's ability to affect gene transcription and to induce apoptosis in preclinical models is likely to be of particular relevance to cancer chemoprevention and chemotherapy in patients. Although curcumin's low systemic bioavailability following oral dosing may limit access of sufficient concentrations for pharmacological effect in certain tissues, the attainment of biologically active levels in the gastrointestinal tract has been demonstrated in animals and humans. Sufficient data currently exist to advocate phase II clinical evaluation of oral curcumin in patients with invasive malignancy or pre-invasive lesions of the gastrointestinal tract, particularly the colon and rectum.",
"title": "Curcumin: the story so far."
},
{
"docid": "MED-2792",
"text": "Two populations of immigrants to London and to the West Indies from the Indian subcontinent have higher than expected morbidity and mortality from atherosclerosis but do not show the commonly accepted major risk factors. This study investigated the hypothesis that ghee, a clarified butter product prized in Indian cooking, contains cholesterol oxides and could therefore be an important source of dietary exposure to cholesterol oxides and an explanation for the high atherosclerosis risk. Substantial amounts of cholesterol oxides were found in ghee (12.3% of sterols), but not in fresh butter, by thin-layer and high-performance-liquid chromatography. Dietary exposure to cholesterol oxides from ghee may offer a logical explanation for the high frequency of atherosclerotic complications in these Indian populations.",
"title": "Cholesterol oxides in Indian ghee: possible cause of unexplained high risk of atherosclerosis in Indian immigrant populations."
},
{
"docid": "MED-4390",
"text": "The medicinal properties of curcumin obtained from Curcuma longa L. cannot be utilised because of poor bioavailability due to its rapid metabolism in the liver and intestinal wall. In this study, the effect of combining piperine, a known inhibitor of hepatic and intestinal glucuronidation, was evaluated on the bioavailability of curcumin in rats and healthy human volunteers. When curcumin was given alone, in the dose 2 g/kg to rats, moderate serum concentrations were achieved over a period of 4 h. Concomitant administration of piperine 20 mg/kg increased the serum concentration of curcumin for a short period of 1-2 h post drug. Time to maximum was significantly increased (P < 0.02) while elimination half life and clearance significantly decreased (P < 0.02), and the bioavailability was increased by 154%. On the other hand in humans after a dose of 2 g curcumin alone, serum levels were either undetectable or very low. Concomitant administration of piperine 20 mg produced much higher concentrations from 0.25 to 1 h post drug (P < 0.01 at 0.25 and 0.5 h; P < 0.001 at 1 h), the increase in bioavailability was 2000%. The study shows that in the dosages used, piperine enhances the serum concentration, extent of absorption and bioavailability of curcumin in both rats and humans with no adverse effects.",
"title": "Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers."
},
{
"docid": "MED-2584",
"text": "In a 6-year prospective study, the authors examined the relation between diet and incident colon cancer among 32,051 non-Hispanic white cohort members of the Adventist Health Study (California, 1976-1982) who, at baseline, had no documented or reported history of cancer. The risk of colon cancer was determined from proportional hazards regression with adjustment for age and other covariates. The authors found a positive association with total meat intake (risk ratio (RR) for > or =1 time/week vs. no meat intake = 1.85, 95% confidence interval (CI) 1.19-2.87; p for trend = 0.01) and, among subjects who favored specific types of meat, positive associations with red meat intake (RR for > or =1 time/week vs. no red meat intake = 1.90, 95% CI 1.16-3.11; p for trend = 0.02) and white meat intake (RR for > or =1 time/week vs. no white meat intake = 3.29, 95% CI 1.60-6.75; p for trend = 0.006). An inverse association with legume intake (RR for >2 times/week vs. <1 time/week = 0.53, 95% CI 0.33-0.86; p for trend = 0.03) was observed. Among men, a positive association with body mass index was observed (relative to the RR for tertile III (>25.6 kg/m2) vs. tertile I (<22.5 kg/m2) = 2.63, 95% CI 1.12-6.13; p for trend = 0.05). A complex relation was identified whereby subjects exhibiting a high red meat intake, a low legume intake, and a high body mass experienced a more than threefold elevation in risk relative to all other patterns based on these variables. This pattern of putative risk factors would likely contribute to increases in both insulin resistance (high body mass, high red meat intake) and glycemic load (low legume intake), a synergism that, if causal, implicates hyperinsulinemic exposure in colon carcinogenesis. The overall findings from this cohort identify both red meat intake and white meat intake as important dietary risk factors for colon cancer and raise the possibility that the risk due to red meat intake reflects a more complex etiology.",
"title": "Dietary risk factors for colon cancer in a low-risk population."
},
{
"docid": "MED-2824",
"text": "Cancer is primarily a disease of old age, and that life style plays a major role in the development of most cancers is now well recognized. While plant-based formulations have been used to treat cancer for centuries, current treatments usually involve poisonous mustard gas, chemotherapy, radiation, and targeted therapies. While traditional plant-derived medicines are safe, what are the active principles in them and how do they mediate their effects against cancer is perhaps best illustrated by curcumin, a derivative of turmeric used for centuries to treat a wide variety of inflammatory conditions. Curcumin is a diferuloylmethane derived from the Indian spice, turmeric (popularly called \"curry powder\") that has been shown to interfere with multiple cell signaling pathways, including cell cycle (cyclin D1 and cyclin E), apoptosis (activation of caspases and down-regulation of antiapoptotic gene products), proliferation (HER-2, EGFR, and AP-1), survival (PI3K/AKT pathway), invasion (MMP-9 and adhesion molecules), angiogenesis (VEGF), metastasis (CXCR-4) and inflammation (NF-kappaB, TNF, IL-6, IL-1, COX-2, and 5-LOX). The activity of curcumin reported against leukemia and lymphoma, gastrointestinal cancers, genitourinary cancers, breast cancer, ovarian cancer, head and neck squamous cell carcinoma, lung cancer, melanoma, neurological cancers, and sarcoma reflects its ability to affect multiple targets. Thus an \"old-age\" disease such as cancer requires an \"age-old\" treatment.",
"title": "Curcumin and cancer: an \"old-age\" disease with an \"age-old\" solution."
},
{
"docid": "MED-2783",
"text": "Although much has been published about curcumin, which is obtained from turmeric, comparatively little is known about turmeric itself. Turmeric, a golden spice obtained from the rhizome of the plant Curcuma longa, has been used to give color and taste to food preparations since ancient times. Traditionally, this spice has been used in Ayurveda and folk medicine for the treatment of such ailments as gynecological problems, gastric problems, hepatic disorders, infectious diseases, and blood disorders. Modern science has provided the scientific basis for the use of turmeric against such disorders. Various chemical constituents have been isolated from this spice, including polyphenols, sesquiterpenes, diterpenes, triterpenoids, sterols, and alkaloids. Curcumin, which constitutes 2-5% of turmeric, is perhaps the most-studied component. Although some of the activities of turmeric can be mimicked by curcumin, other activities are curcumin-independent. Cell-based studies have demonstrated the potential of turmeric as an antimicrobial, insecticidal, larvicidal, antimutagenic, radioprotector, and anticancer agent. Numerous animal studies have shown the potential of this spice against proinflammatory diseases, cancer, neurodegenerative diseases, depression, diabetes, obesity, and atherosclerosis. At the molecular level, this spice has been shown to modulate numerous cell-signaling pathways. In clinical trials, turmeric has shown efficacy against numerous human ailments including lupus nephritis, cancer, diabetes, irritable bowel syndrome, acne, and fibrosis. Thus, a spice originally common in the kitchen is now exhibiting activities in the clinic. In this review, we discuss the chemical constituents of turmeric, its biological activities, its molecular targets, and its potential in the clinic. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",
"title": "Multitargeting by turmeric, the golden spice: From kitchen to clinic."
},
{
"docid": "MED-4544",
"text": "Emblica officinalis Gaertn. or Phyllanthus emblica Linn, commonly known as Indian gooseberry or amla, is arguably the most important medicinal plant in the Indian traditional system of medicine, the Ayurveda. Various parts of the plant are used to treat a range of diseases, but the most important is the fruit. The fruit is used either alone or in combination with other plants to treat many ailments such as common cold and fever; as a diuretic, laxative, liver tonic, refrigerant, stomachic, restorative, alterative, antipyretic, anti-inflammatory, hair tonic; to prevent peptic ulcer and dyspepsia, and as a digestive. Preclinical studies have shown that amla possesses antipyretic, analgesic, antitussive, antiatherogenic, adaptogenic, cardioprotective, gastroprotective, antianemia, antihypercholesterolemia, wound healing, antidiarrheal, antiatherosclerotic, hepatoprotective, nephroprotective, and neuroprotective properties. In addition, experimental studies have shown that amla and some of its phytochemicals such as gallic acid, ellagic acid, pyrogallol, some norsesquiterpenoids, corilagin, geraniin, elaeocarpusin, and prodelphinidins B1 and B2 also possess antineoplastic effects. Amla is also reported to possess radiomodulatory, chemomodulatory, chemopreventive effects, free radical scavenging, antioxidant, anti-inflammatory, antimutagenic and immunomodulatory activities, properties that are efficacious in the treatment and prevention of cancer. This review for the first time summarizes the results related to these properties and also emphasizes the aspects that warrant future research to establish its activity and utility as a cancer preventive and therapeutic drug in humans.",
"title": "Amla (Emblica officinalis Gaertn), a wonder berry in the treatment and prevention of cancer."
},
{
"docid": "MED-2801",
"text": "Turmeric has been long recognized for its anti-inflammatory and health-promoting properties. Curcumin is one of the principal anti-inflammatory and healthful components of turmeric comprising 2-8% of most turmeric preparations. Experimental evidence supports the activity of curcumin in promoting weight loss and reducing the incidence of obesity-related diseases. With the discovery that obesity is characterized by chronic low-grade metabolic inflammation, phytochemicals like curcumin which have anti-inflammatory activity are being intensely investigated. Recent scientific research reveals that curcumin directly interacts with white adipose tissue to suppress chronic inflammation. In adipose tissue, curcumin inhibits macrophage infiltration and nuclear factor κB (NF-κB) activation induced by inflammatory agents. Curcumin reduces the expression of the potent proinflammatory adipokines tumor necrosis factor-α (TNFα), monocyte chemoattractant protein-1 (MCP-1), and plasminogen activator inhibitor type-1 (PAI-1), and it induces the expression of adiponectin, the principal anti-inflammatory agent secreted by adipocytes. Curcumin also has effects to inhibit adipocyte differentiation and to promote antioxidant activities. Through these diverse mechanisms curcumin reduces obesity and curtails the adverse health effects of obesity. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.",
"title": "Curcumin and obesity."
},
{
"docid": "MED-2573",
"text": "A significant anticancer activity of the naturally occurring carbohydrate inositol hexaphosphate (IP(6)) has been reported against numerous cancer models. Since tumors require angiogenesis for growth and metastasis, we hypothesize that IP(6) reduces tumor growth by inhibiting angiogenesis. Because angiogenesis depends on the interaction between endothelial and tumor cells, we investigated the effect of IP(6) on both. IP(6) inhibited the proliferation and induced the differentiation of endothelial cells in vitro; the growth of bovine aortic endothelial cells (BAECs) evaluated by MTT proliferation assay was inhibited in a dose-dependent manner (IC(50) = 0.74 mM). The combination of IP(6) and vasostatin, a calreticulin fragment with anti-angiogenic activity, was synergistically superior in growth inhibition than either compound. IP(6) inhibited human umbilical vein endothelial cell (HUVEC) tube formation (in vitro capillary differentiation) on a reconstituted extracellular matrix, Matrigel, and disrupted pre-formed tubes. IP(6) significantly reduced basic fibroblast growth factor (bFGF)-induced vessel formation (P < 0.01) in vivo in Matrigel plug assay. Exposure of HepG2, a human hepatoma cell line, to IP(6) for 8 h, resulted in a dose-dependent decrease in the mRNA levels of vascular endothelial growth factor (VEGF), as assessed by RT-PCR. IP(6) treatment of HepG2 cells for 24 h also significantly reduced the VEGF protein levels in conditioned medium, in a concentration-dependent manner (P = 0.012). Thus, IP(6) has an inhibitory effect on induced angiogenesis.",
"title": "Anti-angiogenic activity of inositol hexaphosphate (IP6)."
},
{
"docid": "MED-2988",
"text": "This review describes the present state of knowledge about phytic acid (phytate), which is often present in legume seeds. The antinutritional effects of phytic acid primarily relate to the strong chelating associated with its six reactive phosphate groups. Its ability to complex with proteins and particularly with minerals has been a subject of investigation from chemical and nutritional viewpoints. The hydrolysis of phytate into inositol and phosphates or phosphoric acid occurs as a result of phytase or nonenzymatic cleavage. Enzymes capable of hydrolysing phytates are widely distributed in micro-organisms, plants and animals. Phytases act in a stepwise manner to catalyse the hydrolysis of phytic acid. To reduce or eliminate the chelating ability of phytate, dephosphorylation of hexa- and penta-phosphate forms is essential since a high degree of phosphorylation is necessary to bind minerals. There are several methods of decreasing the inhibitory effect of phytic acid on mineral absorption (cooking, germination, fermentation, soaking, autolysis). Nevertheless, inositol hexaphosphate is receiving increased attention owing to its role in cancer prevention and/or therapy and its hypocholesterolaemic effect.",
"title": "The role of phytic acid in legumes: antinutrient or beneficial function?"
},
{
"docid": "MED-2827",
"text": "Alternative and complementary therapeutic approaches, such as the use of a wide array of herbal, nutritional, and physical manipulations, are becoming popular for relieving symptoms of osteoarthritis (OA). The present study evaluated the efficacy of soy protein (SP) supplementation in relieving the pain and discomfort associated with OA. One hundred and thirty-five free-living individuals (64 men and 71 women) with diagnosed OA or with self-reported chronic knee joint pain not attributed to injury or rheumatoid arthritis were recruited for this double-blind, placebo-controlled, parallel design study. Study participants were assigned randomly to consume 40 g of either supplemental SP or milk-based protein (MP) daily for 3 months. Pain, knee range of motion, and overall physical activity were evaluated prior to the start of treatment and monthly thereafter. Serum levels of glycoprotein 39 (YKL-40), a marker of cartilage degradation, and insulin-like growth factor-I (IGF-I), a growth factor associated with cartilage synthesis, were assessed at baseline and at the end of the study. Overall, SP improved OA-associated symptoms such as range of motion and several factors associated with pain and quality of life in comparison to MP. However, these beneficial effects were mainly due to the effect of SP in men rather than women. Biochemical markers of cartilage metabolism further support the efficacy of SP in men as indicated by a significant increase in serum level of IGF-I and a significant decrease in serum level of YKL-40 compared to MP. This study is the first to provide evidence of possible beneficial effects of SP in the management of OA. Examining and verifying the long-term effects of SP on improving symptoms of OA, particularly in men, is warranted.",
"title": "Soy protein may alleviate osteoarthritis symptoms."
}
] |
[
{
"docid": "MED-1819",
"text": "Gemcitabine is a first line cancer drug widely used for the treatment of pancreatic cancer. However, its therapeutic efficiency is significantly limited by resistance of pancreatic cancer cells to this and other chemotherapeutic drugs. We have investigated the cytotoxic effect of Turmeric Force (TF), a supercritical and hydroethanolic extract of turmeric, alone and in combination with gemcitabine in two pancreatic carcinoma cell lines (BxPC3 and Panc-1). TF is highly cytotoxic to BxPC3 and Panc-1 cell lines with IC50 values of 1.0 and 1.22 microg/ml, respectively with superior cytotoxicity than curcumin. Gemcitabine IC50 value for both of these cell line is 0.03 microg/ml; however, 30-48% of the pancreatic cancer cells are resistant to gemcitabine even at concentrations >100 microg/ml. In comparison, TF induced cell death in 96% of the cells at 50 microg/ml. The combination of gemcitabine and TF was synergistic with IC90 levels achieved in both pancreatic cancer cell lines at lower concentrations. CalcuSyn analysis of cytotoxicity data showed that the Gemcitabine + Turmeric Force combination has strong synergism with combination index (CI) values of 0.050 and 0.183 in BxPC3 and Panc-1 lines, respectively at IC50 level. This synergistic effect is due to the increased inhibitory effect of the combination on nuclear factor-kappaB activity and signal transducer and activator of transcription factor 3 expression as compared to the single agent.",
"title": "Potentiation of gemcitabine by Turmeric Force in pancreatic cancer cell lines."
},
{
"docid": "MED-4999",
"text": "Curcumin (Cur), a component of turmeric (Curcuma longa), has been reported to exhibit antimetastatic activities, but the mechanisms remain unclear. Other curcuminoids present in turmeric, demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC) have not been investigated whether they exhibit antimetastatic activity to the same extent as curcumin. The regulation of matrix metalloproteinases (MMPs) and urokinase plasminogen activator (uPA) play important role in cancer cell invasion by cleavage of extracellular matrix (ECM). In this line, we comparatively examined the influence of Cur, DMC and BDMC on the expressions of uPA, MMP-2, MMP-9, membrane Type 1 MMP (MT1-MMP), tissue inhibitor of metalloproteinases (TIMP-2), and in vitro invasiveness of human fibrosarcoma cells. The results indicate that the differential potency for inhibition of cancer cell invasion was BDMC> or =DMC>Cur, whereas the cell migration was not affected. Zymography analysis exhibited that curcumin, DMC and BDMC significantly decreased uPA, active-MMP-2 and MMP-9 but not pro-MMP-2 secretion from the cells in a dose-dependent manner, in which BDMC and DMC show higher potency than curcumin. The suppression of active MMP-2 level correlated with inhibition of MT1-MMP and TIMP-2 protein levels involved in pro-MMP-2 activation. Importantly, BDMC and DMC at 10 microM reduced MT1-MMP and TIMP-2 protein expression, but curcumin slightly reduced only MT1-MMP but not TIMP-2. In addition, three forms of curcuminoids significantly inhibited collagenase, MMP-2, and MMP-9 but not uPA activity. In summary, these data demonstrated that DMC and BDMC show higher antimetastasis potency than curcumin by the differentially down-regulation of ECM degradation enzymes.",
"title": "Curcumin, demethoxycurcumin and bisdemethoxycurcumin differentially inhibit cancer cell invasion through the down-regulation of MMPs and uPA."
},
{
"docid": "MED-5001",
"text": "We examine the possible evidence that the phytochemical curcumin may overcome resistance to hormonal and cytotoxic agents in breast cancer. We present our observations on MCF-7R, a multidrug-resistant (MDR) variant of the MCF-7 breast cancer cell line. In contrast to MCF-7, MCF-7R lacks aromatase and estrogen receptor alpha (ERalpha) and overexpresses the multidrug transporter ABCB1 and the products of different genes implicated in cell proliferation and survival, like c-IAP-1, NAIP, survivin, and COX-2. Nevertheless, in cytotoxicity and cell death induction assays, we found that the antitumor activity of curcumin is substantial both in MCF-7 and in MCF-7R. We elaborated the diketone system of curcumin into different analogues; the benzyloxime and the isoxazole and pyrazole heterocycles showed remarkable increases in the antitumor potency both in the parental and in the MDR MCF-7 cells. Furthermore, curcumin or, more potently, the isoxazole analogue, produced early reductions in the amounts of relevant gene transcripts that were diverse (i.e., they were relative to Bcl-2 and Bcl-X(L) in MCF-7 and the inhibitory of apoptosis proteins and COX-2 in MCF-7R) in the two cell lines. Thus, the two compounds exhibited the remarkable property of being able to modify their molecular activities according to the distinct characteristics of the parental and MDR cells. We discuss also how curcumin may (1) exert antitumor effects in breast cancer through ER-dependent and ER-independent mechanisms; and (2) act as a drug transporter-mediated MDR reversal agent. Overall, the structure of curcumin may represent the basis for the development of new, effective anticancer agents in hormone-independent MDR breast cancer.",
"title": "Curcumin as a possible lead compound against hormone-independent, multidrug-resistant breast cancer."
},
{
"docid": "MED-2243",
"text": "An ethanol extract of turmeric (\"Curcuma longa\") as well as an ointment of curcumin (its active ingredient) were found to produce remarkable symptomatic relief in patients with external cancerous lesions. Reduction in smell were noted in 90% of the cases and reduction in itching in almost all cases. Dry lesions were observed in 70% of the cases, and a small number of patients (10%) had a reduction in lesion size and pain. In many patients the effect continued for several months. An adverse reaction was noticed in only one of the 62 patients evaluated.",
"title": "Turmeric and curcumin as topical agents in cancer therapy."
},
{
"docid": "MED-2239",
"text": "OBJECTIVE: Human papillomavirus (HPV) infections remain a leading cause of mortality worldwide. In the U.S. strategies via screening and vaccination prevent HPV-associated cervical neoplasms, but consume immense healthcare costs. The spice component curcumin has potent anticancer and antiviral properties, which have been difficult to harness as a treatment, due to its poor systemic bioavailability. This project tests the possibility of developing a curcumin-based therapy for cervical cancer. METHODS: Using four HPV(+) cervical cancer cell lines and normal fibroblasts we first tested the selectivity and potency of curcumin in eliminating HPV(+) cells. Subsequently, we developed a curcumin-based cervical cream and tested its efficacy in eliminating apposed HPV(+) cells and also its possible side effects on the vaginal epithelium of healthy mice. RESULTS: Curcumin selectively eliminates a variety of HPV(+) cervical cancer cells (HeLa, ME-180, SiHa, and SW756), suppresses the transforming antigen E6, dramatically inhibits the expression of the pro-cancer protein epidermal growth factor receptor (EGFR), and concomitantly induces p53. Additionally, Vacurin, a uniform colloidal solution of curcumin in a clinically used amphipathic vaginal cream, eliminates apposed HeLa cells while suppressing the expression of EGFR. In mice, daily intravaginal application of Vacurin for three weeks produced no change in body weight and when the mice were sacrificed, the vaginal tract epithelium showed no Vacurin-evoked adverse effects. CONCLUSION: We have developed a curcumin-based vaginal cream, which effectively eradicates HPV(+) cancer cells and does not affect non-cancerous tissue. Our preclinical data support a novel approach for the treatment of cervical HPV infection. Copyright © 2012 Elsevier Inc. All rights reserved.",
"title": "A novel curcumin-based vaginal cream Vacurin selectively eliminates apposed human cervical cancer cells."
},
{
"docid": "MED-4998",
"text": "Curcumin has been reported to have the potential to prevent obesity as well as cancers. The downstream targets regulated by AMP-activated protein kinase (AMPK) for inhibiting adipocyte differentiation or cancer cell proliferation of curcumin were investigated. The activation of AMPK by curcumin was crucial for the inhibition of differentiation or growth in both adipocytes and cancer cells. Stimulation of AMPK by curcumin resulted in the down-regulation of PPAR (peroxisome proliferator-activated receptor)-gamma in 3T3-L1 adipocytes and the decrease in COX-2 in MCF-7 cells. Application of a synthetic AMPK activator also supported the evidence that AMPK acts as an upstream signal of PPAR-gamma in 3T3-L1 adipocytes. In cancer cells, AMPK was found to act as a regulator of ERK1/2, p38, and COX-2. Regulation of AMPK and its downstream targets such as PPAR-gamma, Mapkinases, and COX-2 by curcumin appears to be important in controlling adipocytes and cancerous cells.",
"title": "Curcumin exerts antidifferentiation effect through AMPKalpha-PPAR-gamma in 3T3-L1 adipocytes and antiproliferatory effect through AMPKalpha-COX-2 i..."
},
{
"docid": "MED-2606",
"text": "Curcumin, the active principle of turmeric, is known to act as an anti-oxidant, anti-mutagen and anti-carcinogen in experimental animals. In the present study, anti-mutagenic effects of turmeric were assessed in 16 chronic smokers. It was observed that turmeric, given in doses of 1.5 g/day for 30 days, significantly reduced the urinary excretion of mutagens in smokers. In contrast, in six non-smokers, who served as control, there was no change in the urinary excretion of mutagens after 30 days. Turmeric had no significant effect on serum aspartate aminotransferase and alanine aminotransferase, blood glucose, creatinine and lipid profile. These results indicate that dietary turmeric is an effective anti-mutagen and it may be useful in chemoprevention.",
"title": "Effect of turmeric on urinary mutagens in smokers."
},
{
"docid": "MED-2608",
"text": "The effects of curcumin, the yellow pigment of the spice, turmeric (Curcuma longa) on the mutagenicity of several environmental mutagens were investigated in the Salmonella/microsome test with or without Aroclor 1254-induced rat-liver homogenate (S-9 mix). With Salmonella typhimurium strain TA98 in the presence of S-9 mix, curcumin inhibited the mutagenicity of bidi and cigarette smoke condensates, tobacco and masheri extracts, benzo[a]pyrne and dimethyl benzo[a]anthracene in a dose-dependent manner. Curcumin did not influence the mutagenicity without S-9 mix of sodium azide, monoacetylhydrazine and streptozocin in strain TA100 nor of 4-nitrophenylenediamine in strain TA98. Our observations indicate that curcumin may alter the metabolic activation and detoxification of mutagens.",
"title": "In vitro antimutagenicity of curcumin against environmental mutagens."
},
{
"docid": "MED-1507",
"text": "Vascular endothelial function is declines with aging and is associated with an increased risk of cardiovascular disease. Lifestyle modification, particularly aerobic exercise and dietary adjustment, has a favorable effect on vascular aging. Curcumin is a major component of turmeric with known anti-inflammatory and anti-oxidative effects. We investigated the effects of curcumin ingestion and aerobic exercise training on flow-mediated dilation as an indicator endothelial function in postmenopausal women. A total of 32 postmenopausal women were assigned to 3 groups: control, exercise, and curcumin groups. The curcumin group ingested curcumin orally for 8 weeks. The exercise group underwent moderate aerobic exercise training for 8 weeks. Before and after each intervention, flow-mediated dilation was measured. No difference in baseline flow-mediated dilation or other key dependent variables were detected among the groups. Flow-mediated dilation increased significantly and equally in the curcumin and exercise groups, whereas no changes were observed in the control group. Our results indicated that curcumin ingestion and aerobic exercise training can increase flow-mediated dilation in postmenopausal women, suggesting that both can potentially improve the age-related decline in endothelial function. Copyright © 2012 Elsevier Inc. All rights reserved.",
"title": "Curcumin ingestion and exercise training improve vascular endothelial function in postmenopausal women."
},
{
"docid": "MED-1813",
"text": "PURPOSE: Pancreatic cancer is almost always lethal, and the only U.S. Food and Drug Administration-approved therapies for it, gemcitabine and erlotinib, produce objective responses in <10% of patients. We evaluated the clinical biological effects of curcumin (diferuloylmethane), a plant-derived dietary ingredient with potent nuclear factor-kappaB (NF-kappaB) and tumor inhibitory properties, against advanced pancreatic cancer. EXPERIMENTAL DESIGN: Patients received 8 g curcumin by mouth daily until disease progression, with restaging every 2 months. Serum cytokine levels for interleukin (IL)-6, IL-8, IL-10, and IL-1 receptor antagonists and peripheral blood mononuclear cell expression of NF-kappaB and cyclooxygenase-2 were monitored. RESULTS: Twenty-five patients were enrolled, with 21 evaluable for response. Circulating curcumin was detectable as drug in glucuronide and sulfate conjugate forms, albeit at low steady-state levels, suggesting poor oral bioavailability. Two patients showed clinical biological activity. One had ongoing stable disease for >18 months; interestingly, one additional patient had a brief, but marked, tumor regression (73%) accompanied by significant increases (4- to 35-fold) in serum cytokine levels (IL-6, IL-8, IL-10, and IL-1 receptor antagonists). No toxicities were observed. Curcumin down-regulated expression of NF-kappaB, cyclooxygenase-2, and phosphorylated signal transducer and activator of transcription 3 in peripheral blood mononuclear cells from patients (most of whom had baseline levels considerably higher than those found in healthy volunteers). Whereas there was considerable interpatient variation in plasma curcumin levels, drug levels peaked at 22 to 41 ng/mL and remained relatively constant over the first 4 weeks. CONCLUSIONS: Oral curcumin is well tolerated and, despite its limited absorption, has biological activity in some patients with pancreatic cancer.",
"title": "Phase II trial of curcumin in patients with advanced pancreatic cancer."
},
{
"docid": "MED-2245",
"text": "Curcumin (diferuloylmethane) is being considered as a potential chemopreventive agent in humans. In vitro it inhibits transcription by NF-kappaB, and the activity of lipoxygenase or cyclooxygenase enzymes, which facilitate tumor progression. In vivo it is protective in rodent models of chemical carcinogenesis. Curcumin contains an alpha,beta-unsaturated ketone, a reactive chemical substituent that is responsible for its repression of NF-kappaB. In compounds other than curcumin this same electrophilic moiety is associated with inactivation of the tumor suppressor, p53. Here we report that curcumin behaves analogously to these compounds. It disrupts the conformation of the p53 protein required for its serine phosphorylation, its binding to DNA, its transactivation of p53-responsive genes and p53-mediated cell cycle arrest.",
"title": "Curcumin impairs tumor suppressor p53 function in colon cancer cells."
},
{
"docid": "MED-2246",
"text": "Curcuma spp. extracts, particularly the dietary polyphenol curcumin, prevent colon cancer in rodents. In view of the sparse information on the pharmacodynamics and pharmacokinetics of curcumin in humans, a dose-escalation pilot study of a novel standardized Curcuma extract in proprietary capsule form was performed at doses between 440 and 2200 mg/day, containing 36-180 mg of curcumin. Fifteen patients with advanced colorectal cancer refractory to standard chemotherapies received Curcuma extract daily for up to 4 months. Activity of glutathione S-transferase and levels of a DNA adduct (M(1)G) formed by malondialdehyde, a product of lipid peroxidation and prostaglandin biosynthesis, were measured in patients' blood cells. Oral Curcuma extract was well tolerated, and dose-limiting toxicity was not observed. Neither curcumin nor its metabolites were detected in blood or urine, but curcumin was recovered from feces. Curcumin sulfate was identified in the feces of one patient. Ingestion of 440 mg of Curcuma extract for 29 days was accompanied by a 59% decrease in lymphocytic glutathione S-transferase activity. At higher dose levels, this effect was not observed. Leukocytic M(1)G levels were constant within each patient and unaffected by treatment. Radiologically stable disease was demonstrated in five patients for 2-4 months of treatment. The results suggest that (a) Curcuma extract can be administered safely to patients at doses of up to 2.2 g daily, equivalent to 180 mg of curcumin; (b) curcumin has low oral bioavailability in humans and may undergo intestinal metabolism; and (c) larger clinical trials of Curcuma extract are merited.",
"title": "Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer."
},
{
"docid": "MED-3724",
"text": "Drug resistance remains an on-going challenge in ovarian cancer chemotherapy. The objective of this study was to determine the effect on synergism in activity from the sequenced combinations of cisplatin (Cis) with curcumin (Cur) and epigallocatechin-3-gallate (EGCG) in the human ovarian cancer cell lines. The drugs were added in binary combinations: Cis combined with Cur, and Cis combined with EGCG to the human ovarian A2780 and A2780(cisR) cancer cell lines, using five different sequences of administration: 0/0 h, 4/0 h, 0/4 h, 24/0 h and 0/24 h. The combination index (CI) was used to assess the combined action of the drugs. CIs <1, =1 and >1 indicated synergism, additiveness and antagonism respectively. Cellular accumulation of platinum and platinum-DNA binding levels from Cis and its combination with the phytochemicals were determined using graphite furnace atomic absorption spectrometry. Addition of Cis 4 h before Cur and EGCG (0/4 h combination) produced the most synergistic outcomes in both the A2780 and A2780(cisR) cell lines. The cellular accumulations of platinum and platinum-DNA binding resulting from the 0/4 h combinations were greater as compared to the values using Cis alone, thus providing an explanation for the synergistic action. When sequenced combinations of Cis with Cur and with EGCG are applied to human ovarian A2780 and A2780(cisR) cancer cell lines, lower concentrations and shorter time gap between the two additions seem to produce a higher cytotoxic effect.",
"title": "Synergism from sequenced combinations of curcumin and epigallocatechin-3-gallate with cisplatin in the killing of human ovarian cancer cells."
},
{
"docid": "MED-1112",
"text": "Because of the central role of the transcription factor nuclear factor-kappaB (NF-kappaB) in cell survival and proliferation in human multiple myeloma (MM), we explored the possibility of using it as a target for MM treatment by using curcumin (diferuloylmethane), an agent known to have very little or no toxicity in humans. We found that NF-kappaB was constitutively active in all human MM cell lines examined and that curcumin, a chemopreventive agent, down-regulated NF-kappaB in all cell lines as indicated by electrophoretic mobility gel shift assay and prevented the nuclear retention of p65 as shown by immunocytochemistry. All MM cell lines showed consitutively active IkappaB kinase (IKK) and IkappaBalpha phosphorylation. Curcumin suppressed the constitutive IkappaBalpha phosphorylation through the inhibition of IKK activity. Curcumin also down-regulated the expression of NF-kappaB-regulated gene products, including IkappaBalpha, Bcl-2, Bcl-x(L), cyclin D1, and interleukin-6. This led to the suppression of proliferation and arrest of cells at the G(1)/S phase of the cell cycle. Suppression of NF-kappaB complex by IKKgamma/NF-kappaB essential modulator-binding domain peptide also suppressed the proliferation of MM cells. Curcumin also activated caspase-7 and caspase-9 and induced polyadenosine-5'-diphosphate-ribose polymerase (PARP) cleavage. Curcumin-induced down-regulation of NF-kappaB, a factor that has been implicated in chemoresistance, also induced chemosensitivity to vincristine and melphalan. Overall, our results indicate that curcumin down-regulates NF-kappaB in human MM cells, leading to the suppression of proliferation and induction of apoptosis, thus providing the molecular basis for the treatment of MM patients with this pharmacologically safe agent.",
"title": "Curcumin (diferuloylmethane) down-regulates the constitutive activation of nuclear factor-kappa B and IkappaBalpha kinase in human multiple myeloma..."
},
{
"docid": "MED-4461",
"text": "The objective of this study was to investigate, whether the plant-derived isothiocyanate Sulforaphane (SFN) enhances the antitumor activities of the chemotherapeutic agent oxaliplatin (Ox) in a cell culture model of colorectal cancer. Caco-2 cells were cultured under standard conditions and treated with increasing concentrations of SFN [1-20 μM] and/or Ox [100 nM-10 μM]. For co-incubation, cells were pre-treated with SFN for 24 h. Cell growth was determined by BrdU incorporation. Drug interactions were assessed using the combination-index method (CI) (Cl < 1 indicates synergism). Apoptotic events were characterized by different ELISA techniques. Protein levels were examined by Western blot analysis. Annexin V- and propidium iodide (PI) staining followed by FACS analysis was used to differentiate between apoptotic and necrotic events. SFN and Ox alone inhibited cell growth of Caco-2 cells in a dose-dependent manner, an effect, which could be synergistically enhanced, when cells were incubated with the combination of both agents. Co-treated cells further displayed distinctive morphological changes that occurred during the apoptotic process, such as cell surface exposure of phosphatidylserine, membrane blebbing as well as the occurence of cytoplasmic histone-associated DNA fragments. Further observations thereby pointed toward simultaneous activation of both extrinsic and intrinsic apoptotic pathways. With increasing concentrations and treatment duration, a shift from apoptotic to necrotic cell death could be observed. In conclusion, the data suggest that the isothiocyanate SFN sensitizes colon cancer cells to Ox-induced cell growth inhibition via induction of different modes of cell death.",
"title": "Sulforaphane potentiates oxaliplatin-induced cell growth inhibition in colorectal cancer cells via induction of different modes of cell death."
},
{
"docid": "MED-2240",
"text": "Curcumin interacts with a large number of extra- and intracellular targets in a biphasic dose-dependent manner. It controls inflammation, oxidative stress, cell survival, cell secretion, homeostasis, and proliferation. Its mechanisms of action are generally directed toward cells that exhibit disordered physiology or blatant mutation-based abnormal states. Optimizing preventative or therapeutic applications require delivering appropriate quantities of curcumin to lesioned cellular targets. Since diseased conditions anatomically are located from topical to systemic sites, efficient application of curcumin requires specific lesion-oriented delivery methods, representatives of which are here reviewed. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.",
"title": "Curcumin (diferuloylmethane) delivery methods: a review."
},
{
"docid": "MED-938",
"text": "Saffron (dried stigmas of Crocus sativus L.) has been used as a spice, food colorant and medicinal plant for millennia. In this study cytotoxic effect of saffron extract was evaluated in HepG2 and HeLa cell lines. Meanwhile role of apoptosis and ROS were explored. Malignant and non-malignant cells (L929) were cultured in DMEM medium and incubated with different concentrations of ethanolic saffron extract. Cell viability was quantitated by MTT assay. Apoptotic cells were determined using PI staining of DNA fragmentation by flow cytometry (sub-G1 peak). ROS was measured using DCF-DA by flow cytometry analysis. Saffron could decrease cell viability in malignant cells as a concentration and time-dependent manner. The IC50 values against HeLa and HepG2 were determined 800 and 950 microg/ml after 48 h, respectively. Saffron induced a sub-G1 peak in flow cytometry histogram of treated cells compared to control indicating apoptotic cell death is involved in saffron toxicity. This toxicity was also independent of ROS production. It might be concluded that saffron could cause cell death in HeLa and HepG2 cells, in which apoptosis or programmed cell death plays an important role. Saffron could be also considered as a promising chemotherapeutic agent in cancer treatment in future.",
"title": "Study of cytotoxic and apoptogenic properties of saffron extract in human cancer cell lines."
},
{
"docid": "MED-1942",
"text": "Curcumin, from the curry spice turmeric, has been shown to possess potent antioxidant and antiinflammatory properties and to reduce beta-amyloid and plaque burden in experimental studies, but epidemiologic evidence is lacking. The authors investigated the association between usual curry consumption level and cognitive function in elderly Asians. In a population-based cohort (n = 1,010) of nondemented elderly Asian subjects aged 60-93 years in 2003, the authors compared Mini-Mental State Examination (MMSE) scores for three categories of regular curry consumption, taking into account known sociodemographic, health, and behavioral correlates of MMSE performance. Those who consumed curry \"occasionally\" and \"often or very often\" had significantly better MMSE scores than did subjects who \"never or rarely\" consumed curry. The authors reported tentative evidence of better cognitive performance from curry consumption in nondemented elderly Asians, which should be confirmed in future studies.",
"title": "Curry consumption and cognitive function in the elderly."
},
{
"docid": "MED-1811",
"text": "BACKGROUND: A growing number of preclinical studies have demonstrated that curcumin could be a promising anticancer drug; however, poor bioavailability has been the major obstacle for its clinical application. To overcome this problem, we developed a new form of curcumin (Theracurmin) and reported high plasma curcumin levels could be safely achieved after a single administration of Theracurmin in healthy volunteers. In this study, we aimed to evaluate the safety of repetitive administration of Theracurmin in cancer patients. METHODS: Pancreatic or biliary tract cancer patients who failed standard chemotherapy were eligible for this study. Based on our previous pharmacokinetic study, we selected Theracurmin containing 200 mg of curcumin (Level 1) as a starting dose, and the dose was safely escalated to Level 2, which contained 400 mg of curcumin. Theracurmin was orally administered every day with standard gemcitabine-based chemotherapy. In addition to safety and pharmacokinetics data, NF-κB activity, cytokine levels, efficacy, and quality-of-life score were evaluated. RESULTS: Ten patients were assigned to level 1 and six were to level 2. Peak plasma curcumin levels (median) after Theracurmin administration were 324 ng/mL (range, 47-1,029 ng/mL) at Level 1 and 440 ng/mL (range, 179-1,380 ng/mL) at Level 2. No unexpected adverse events were observed and 3 patients safely continued Theracurmin administration for >9 months. CONCLUSIONS: Repetitive systemic exposure to high concentrations of curcumin achieved by Theracurmin did not increase the incidence of adverse events in cancer patients receiving gemcitabine-based chemotherapy.",
"title": "A phase I study investigating the safety and pharmacokinetics of highly bioavailable curcumin (Theracurmin) in cancer patients."
},
{
"docid": "MED-1110",
"text": "PURPOSE: To determine the effect of curcumin on plasma cells and osteoclasts in patients with MGUS. EXPERIMENTAL DESIGN: Twenty-six patients with MGUS were recruited into the study and administered 4 grams/day oral curcumin. Blood and urine samples were collected at specified visits after initiating therapy. Full blood count, B2 microglobulin, serum paraprotein, and immunoglobulin electrophoresis (IEPG and EPG) were determined for all patients at each visit. Serum calcium, 25 hydroxyvitamin D3, and bone-specific alkaline phosphatase were determined at baseline only. Urine, as a morning second-void sample, was collected at each visit for urinary N-telopeptide of type I collagen. RESULTS: Our results show that oral curcumin is able to decrease paraprotein load in a select group (i.e., those having a paraprotein level of >20 g/L) of patients with MGUS. Fifty percent (5 of 10) of these patients had a 12% to 30% reduction in their paraprotein levels, while on curcumin therapy. In addition, 27% of patients on curcumin had a >25% decrease in urinary N-telopeptide of type I collagen. CONCLUSION: Due to the possible progression of MGUS to multiple myeloma, the potential role of curcumin as a therapeutic intervention for MGUS patients warrants further investigation.",
"title": "The potential role of curcumin in patients with monoclonal gammopathy of undefined significance--its effect on paraproteinemia and the urinary N-te..."
},
{
"docid": "MED-2427",
"text": "Lipid rafts/caveolae are membrane platforms for signaling molecules that regulate various cellular functions, including cell survival. To better understand the role of rafts in tumor progression and therapeutics, we investigated the effect of raft disruption on cell viability and compared raft levels in human cancer cell lines versus their normal counterparts. Here, we report that cholesterol depletion using methyl-β cyclodextrin caused anoikis-like apoptosis, which in A431 cells involved decreased raft levels, Bcl-xL down-regulation, caspase-3 activation, and Akt inactivation regardless of epidermal growth factor receptor activation. Cholesterol repletion replenished rafts on the cell surface and restored Akt activation and cell viability. Moreover, the breast cancer and the prostate cancer cell lines contained more lipid rafts and were more sensitive to cholesterol depletion-induced cell death than their normal counterparts. These results indicate that cancer cells contain increased levels of rafts and suggest a potential use of raft-modulating agents as anti-cancer drugs.",
"title": "Elevated Levels of Cholesterol-Rich Lipid Rafts in Cancer Cells Are Correlated with Apoptosis Sensitivity Induced by Cholesterol-Depleting Agents"
},
{
"docid": "MED-3947",
"text": "Hibiscus sabdariffa Linne (Malvaceae), an attractive plant believed to be native to Africa, is cultivated in the Sudan and Eastern Taiwan. Anthocyanins exist widely in many vegetables and fruits. Some reports demonstrated that anthocyanins extracted from H. sabdariffa L., Hibiscus anthocyanins (HAs) (which are a group of natural pigments existing in the dried calyx of H. sabdariffa L.) exhibited antioxidant activity and liver protection. Therefore, in this study, we explored the effect of HAs on human cancer cells. The result showed that HAs could cause cancer cell apoptosis, especially in HL-60 cells. Using flow cytometry, we found that HAs treatment (0-4 mg/ml) markedly induced apoptosis in HL-60 cells in a dose- and time-dependent manner. The result also revealed increased phosphorylation in p38 and c-Jun, cytochrome c release, and expression of tBid, Fas, and FasL in the HAs-treated HL-60 cells. We further used SB203580 (p38 inhibitor), PD98059 (MEK inhibitor), SP600125 (JNK inhibitor), and wortmannin (phosphatidylinositol 3-kinase; PI-3K inhibitor) to evaluate their effect on the HAs-induced HL-60 death. The data showed that only SB203580 had strong potential in inhibiting HL-60 cell apoptosis and related protein expression and phosphorylation. Therefore, we suggested that HAs mediated HL-60 apoptosis via the p38-FasL and Bid pathway. According to these results, HAs could be developed as chemopreventive agents. However, further investigations into the specificity and mechanism(s) of HAs are needed.",
"title": "Hibiscus anthocyanins rich extract-induced apoptotic cell death in human promyelocytic leukemia cells."
},
{
"docid": "MED-2044",
"text": "Cancer incidence increases with advancing age. Over 60% of new cancers and 70% of cancer deaths occur in individuals aged 65 years or older. One factor that may contribute to this is immunosenescence - a canopy term that is used to describe age-related declines in the normal functioning of the immune system. There are multiple age-related deficits in both the innate and adaptive systems that may play a role in the increased incidence of cancer. These include decreased NK-cell function, impaired antigen uptake and presentation by monocytes and dendritic cells, an increase in 'inflammaging', a decline in the number of naïve T-cells able to respond to evolving tumor cells, and an increase in functionally exhausted senescent cells. There is consensus that habitual physical exercise can offer protection against certain types of cancer; however the evidence linking immunological mechanisms, exercise, and reduced cancer risk remain tentative. Multiple studies published over the last two decades suggest that exercise can mitigate the deleterious effects of age on immune function, thus increasing anti-cancer immunity. The potential ameliorative effect of exercise on these mechanisms include evidence that physical activity is able to stimulate greater NK-cell activity, enhance antigen-presentation, reduce inflammation, and prevent senescent cell accumulation in the elderly. Here we discuss the role played by the immune system in preventing and controlling cancer and how aging may retard these anti-cancer mechanisms. We also propose a pathway by which exercise-induced alterations in immunosenescence may decrease the incidence of cancer and help improve prognosis in cancer patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.",
"title": "Can exercise-related improvements in immunity influence cancer prevention and prognosis in the elderly?"
},
{
"docid": "MED-874",
"text": "BACKGROUND: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent which selectively kills cancer cells with little effect on normal cells. However, TRAIL resistance is widely found in cancer cells. We have previously reported antimetatstatic and antiangiogenic effects of vanillin, a flavoring agent from vanilla. Here we have evaluated the sensitizing effect of vanillin on a TRAIL-resistant human cervical cancer cell line, HeLa. MATERIALS AND METHODS: Cell viability after treatments was determined by the WST-1 cell counting kit. Apoptosis was demonstrated by detection of caspase-3 activation and cleavage of poly (ADP-ribose) polymerase using immunoblot analysis. Effect of treatments on TRAIL signaling pathway and nuclear factor kappaB (FN-kappaB) activation was studied using immunoblot analysis and luciferase reporter assay. RESULTS: Pretreatment of HeLa cells with vanillin enhanced TRAIL-induced cell death through the apoptosis pathway. Vanillin pretreatment inhibited TRAIL-induced phosphorylation of p65 and transcriptional activity of NF-kappaB. CONCLUSION: Vanillin sensitizes HeLa cells to TRAIL-induced apoptosis by inhibiting NF-kappaB activation.",
"title": "Vanillin enhances TRAIL-induced apoptosis in cancer cells through inhibition of NF-kappaB activation."
},
{
"docid": "MED-865",
"text": "Prostate cancer remains the second leading cause of cancer deaths among American men. Earlier diagnosis increases survival rate in patients. However, treatments for advanced disease are limited to hormone ablation techniques and palliative care. Thus, new methods of treatment and prevention are necessary for inhibiting disease progression to a hormone refractory state. One of the approaches to control prostate cancer is prevention through diet, which inhibits one or more neoplastic events and reduces the cancer risk. For centuries, Ayurveda has recommended the use of bitter melon (Momordica charantia) as a functional food to prevent and treat human health related issues. In this study, we have initially used human prostate cancer cells, PC3 and LNCaP, as an in vitro model to assess the efficacy of bitter melon extract (BME) as an anti-cancer agent. We observed that prostate cancer cells treated with BME accumulate during the S phase of the cell cycle, and modulate cyclin D1, cyclin E and p21 expression. Treatment of prostate cancer cells with BME enhanced Bax expression, and induced poly(ADP-ribose) polymerase cleavage. Oral gavage of BME, as a dietary compound, delayed the progression to high grade prostatic intraepithelial neoplasia (PIN) in TRAMP (transgenic adenocarcinoma of mouse prostate) mice (31%). Prostate tissue from BME-fed mice displayed ~51% reduction of PCNA expression. Together, our results suggest for the first time that oral administration of BME inhibits prostate cancer progression in TRAMP mice by interfering cell cycle progression and proliferation.",
"title": "Bitter melon extract impairs prostate cancer cell cycle progression and delays prostatic intraepithelial neoplasia in TRAMP model"
},
{
"docid": "MED-1512",
"text": "BACKGROUND: Lifestyle modification (i.e., regular physical activity and diet) is effective in preventing the age-related increase in cardiovascular disease risks. Potential therapeutic effects of curcumin (diferuloylmethane) have been confirmed on various diseases, including cancer and Alzheimer's disease, but the effects of curcumin have not been tested on central arterial hemodynamics. The aim of this pilot study was to test the hypothesis that the regular endurance exercise combined with daily curcumin ingestion lowers the age-related increase in left ventricular (LV) afterload to a greater extent than monotherapy with either intervention alone in postmenopausal women using a randomized, double-blind, placebo-controlled, parallel manner. METHODS: Forty-five women were randomly assigned to four interventions: \"placebo ingestion\" (n = 11), \"curcumin ingestion\" (n = 11), \"exercise training with placebo ingestion\" (n = 11), or \"exercise training with curcumin ingestion\" (n = 12). Curcumin or placebo pills (150 mg/day) were administered for 8 weeks. Aortic blood pressure (BP) and augmentation index (AIx), an index of LV afterload, were evaluated by pulse wave analysis from tonometrically measured radial arterial pressure waveforms. RESULTS: There were no significant differences in baseline hemodynamic variables among four groups. After the interventions, brachial systolic BP (SBP) significantly decreased in both exercise-trained groups (P < 0.05 for both), whereas aortic SBP significantly decreased only in the combined-treatment (e.g., exercise and curcumin) group (P < 0.05). Heart rate (HR) corrected aortic AIx significantly decreases only in the combined-treatment group. CONCLUSIONS: These findings suggest that regular endurance exercise combined with daily curcumin ingestion may reduce LV afterload to a greater extent than monotherapy with either intervention alone in postmenopausal women.",
"title": "Effect of endurance exercise training and curcumin intake on central arterial hemodynamics in postmenopausal women: pilot study."
},
{
"docid": "MED-4711",
"text": "Licorice is a common Chinese medicinal herb with antitumor activity. Some components in licorice root have been shown to induce cell cycle arrest or apoptosis in cancer cells. This paper demonstrates for the first time that licorice Glycyrrhiza glabra and its component licochalcone-A (LA) can induce autophagy in addition to apoptosis in human LNCaP prostate cancer cells. Exposure of cells to licorice or LA resulted in several confirmed characteristics of autophagy, including the appearance of autophagic vacuoles revealed by monodansylcadaverine (MDC) staining, formation of acidic vesicular organelles (AVOs), and autophagosome membrane association of microtubule-associated protein 1 light chain 3 (LC3) characterized by cleavage of LC3 and its punctuate redistribution, as well as ultrastructural observation of autophagic vacuoles by transmission electron microscopy. Autophagy induction was accompanied by down-regulation of Bcl-2 and inhibition of the mammalian target of rapamycin (mTOR) pathway. In summary, licorice can induce caspase-dependent and autophagy-related cell death in LNCaP cells.",
"title": "Licorice and licochalcone-A induce autophagy in LNCaP prostate cancer cells by suppression of Bcl-2 expression and the mTOR pathway."
},
{
"docid": "MED-3548",
"text": "Cancer metastasis refers to the spread of cancer cells from the primary neoplasm to distant sites, where secondary tumors are formed, and is the major cause of death from cancer. Natural phytochemicals containing phenolic compounds have been widely demonstrated to have the capability to prevent cancer metastasis. Among phenolic compounds, flavonoids are a very large subclass, and they are abundant in food and nutraceuticals. The number of reports demonstrating that flavonoids are an effective natural inhibitor of cancer invasion and metastasis is increasing in the scientific literature. Catechin derivatives, (−)-epigallocatechin-3-gallate, (−)-epigallocatechin, (−)-epicatechin-3-gallate,and (−)-epicatechin, are the most studied compounds in this topic so far; genistein/genistin, silibinin, quercetin, and anthocyanin have also been widely investigated for their inhibitory activities on invasion/metastasis. Other flavonoids in dietary vegetable foods that are responsible for anti-invasive and anti-metastatic activities of tumors include luteolin,apigenin, myricetin, tangeretin, kaempferol, glycitein, licoricidin,daidzein, and naringenin. To effectively overcome the metastatic cascade, including cell-cell attachment, tissue barrier degradation, migration, invasion, cell-matrix adhesion,and angiogenesis, it is essential that a bioactive compound prevent tumor cells from metastasizing. This review summarizes the effects of flavonoids on the metastatic cascade and the related proteins, the in vitro anti-invasive activity of flavonoids against cancer cells, and the effects of flavonoids on antiangiogenic and in vivo anti-metastatic models. The available scientific evidence indicates that flavonoids are a ubiquitous dietary phenolics subclass and exert extensive in vitro anti-invasive and in vivo anti-metastatic activities.",
"title": "Flavonoids, a ubiquitous dietary phenolic subclass, exert extensive in vitro anti-invasive and in vivo anti-metastatic activities."
},
{
"docid": "MED-4907",
"text": "Tumor metastasis is the most important cause of cancer death and various treatment strategies have targeted on preventing the occurrence of metastasis. Anthocyanins are natural colorants belonging to the flavonoid family, and are wildly used for their antioxidant properties. Here, we provided molecular evidence associated with the anti-metastatic effects of peonidin 3-glucoside and cyanidin 3-glucoside, major anthocyanins extracted from black rice (Oryza sativa L. indica), by showing a marked inhibition on the invasion and motility of SKHep-1 cells. This effect was associated with a reduced expression of matrix metalloproteinase (MMP)-9 and urokinase-type plasminogen activator (u-PA). Peonidin 3-glucoside and cyanidin 3-glucoside also exerted an inhibitory effect on the DNA binding activity and the nuclear translocation of AP-1. Furthermore, these compounds also exerted an inhibitory effect of cell invasion on various cancer cells (SCC-4, Huh-7, and HeLa). Finally, anthocyanins from O. sativa L. indica (OAs) were evidenced by its inhibition on the growth of SKHep-1 cells in vivo.",
"title": "Black rice anthocyanins inhibit cancer cells invasion via repressions of MMPs and u-PA expression."
},
{
"docid": "MED-2244",
"text": "BACKGROUND & AIMS: Familialadenomatous polyposis (FAP) is an autosomal-dominant disorder characterized by the development of hundreds of colorectal adenomas and eventual colorectal cancer. Regression of adenomas in this syndrome occurs with the administration of nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors, but these compounds can have considerable side effects. We evaluated the efficacy of the combination of diet-derived nonprescription supplements curcumin and quercetin to regress adenomas in patients with FAP. METHODS: Five FAP patients with prior colectomy (4 with retained rectum and 1 with an ileal anal pouch) received curcumin 480 mg and quercetin 20 mg orally 3 times a day. The number and size of polyps were assessed at baseline and after therapy. The Wilcoxon signed-rank test was used to determine differences in the number and size of polyps. Treatment side effects and medication compliance also were evaluated. RESULTS: All 5 patients had a decreased polyp number and size from baseline after a mean of 6 months of treatment with curcumin and quercetin. The mean percent decrease in the number and size of polyps from baseline was 60.4% (P < .05) and 50.9% (P < .05), respectively. Minimal adverse side effects and no laboratory abnormalities were noted. CONCLUSIONS: The combination of curcumin and quercetin appears to reduce the number and size of ileal and rectal adenomas in patients with FAP without appreciable toxicity. Randomized controlled trials are needed to validate these findings.",
"title": "Combination treatment with curcumin and quercetin of adenomas in familial adenomatous polyposis."
}
] |
7640
|
What happens when a company stops trading? (pink sheets)
|
[
{
"docid": "350095",
"text": "\"What will happen if the stock price just continues to decline? Nothing. What would happen if folks just stop trading it? Nothing. What if the company goes private? Then they will have to buy you out based on some agreed upon price, as voted by the board and (potentially) approved by the shareholders. Depending on the corporation charter, the board may not be required to seek the shareholders' approval, but if the price the board agreed upon is unreasonable you can sue and prevent the transaction. How do they decide the fair value of the outstanding stocks? Through a process called \"\"valuation\"\", there are accounting firms which specialize in this area of public accounting.\"",
"title": ""
}
] |
[
{
"docid": "278889",
"text": "\"Changing my answer based on clarification in comments. It appears that some of the securities you mentioned, including GEAPP, are traded on what is colloquially known as the Grey Market. Grey Sheets, and also known as the \"\"Gray Market\"\" is another category of OTC stocks that is completely separate from Pink Sheets and the OTCBB. From investopedia The grey market is an over-the-counter market where dealers may execute orders for preferred customers as well as provide support for a new issue before it is actually issued. This activity allows underwriters and the issuer to determine demand and price the securities accordingly before the IPO. Some additional information on this type of stocks. (Source) Unlike other financial markets... No recent bid or ask quotes are available because no market makers share data or quote such stocks. There is no quoting system available to record and settle trades. All Grey sheet trading is moderated by a broker and done between consenting individuals at a price they agree on. The only documentation that can be publicly found regarding the trades is when the last trade took place. No SEC registration and little SEC regulation. Regulation of Grey Sheet stocks takes place mainly on a state level. Unlike Pink Sheets, these stocks have no SEC registration to possess a stock symbol or to possess shares or trade shares of that stock. Such penny stocks, similar to Pink Sheets, are not required to file SEC (Securities and Exchange Commission) financial and business reports. These stocks may not be solicited or advertised to the public unless a certain number of shares are qualified to be traded publicly under 504 of Regulation D. Extremely Illiquid. Gray sheet trading is infrequent, and for good reason... Difficult to trade, not advertised, difficult to follow the price, the least regulation possible, hard to find any information on the stock, very small market cap, little history, and most such stocks do not yet offer public shares. The lack of information (bids, history, financial reports) alone causes most investors to be very skeptical of Gray Sheets and avoid them altogether. Gray Sheets are commonly associated with Initial public offering (IPO) stocks or start up companies or spin-off companies, even though not all are IPO's, start-ups or spin-offs. Grey Sheets is also Home to delisted stocks from other markets. Some stocks on this financial market were once traded on the NASDAQ, OTCBB, or the Pink Sheets but ran into serious misfortune - usually financial - and thus failed to meet the minimum requirements of the registered SEC filings and/or stock exchange regulations for a financial market. Such stocks were delisted or removed and may begin trading on the Grey Sheets. So to answer your question, I think the cause of the wild swings is that: Great question, BTW.\"",
"title": ""
},
{
"docid": "107227",
"text": "popularity that you are referring to is just known as liquidity when discussing markets. More liquid securities tend to trade more shares per day and have very tight bid/ask spreads as many investors are buying and selling the shares at one time. Some larger securities, especially on exchanges, further enhance liquidity by providing market makers. These are individuals on the NYSE, for example, that will make the market in large securities by handling large orders and providing liquidity through their own book of capital. The individuals on the floor on the NYSE you often see on TV are those market makers. However, as trading becomes more electronic, market markers are becoming less and less required. A previous comment suggested pink sheets are risky companies. This is not entirely factual. While the majority of pink sheets are very highly risky companies, many very solid international companies trade their ADRs (American Depository Receipt) on the pink sheets to avoid the high cost of setting up a large exchange at the NYSE and register and report through the SEC. As a TD Ameritrade user, I would be willing to help you out if you have any other questions.",
"title": ""
},
{
"docid": "261640",
"text": "\"The penny/pink sheet stocks you tend to see promoted are the ones a) with small public floats or, b) they are thinly traded. This means that any appreciable change in buy/sell volume will have an outsized effect on the stock's share price, even when the underlying fundamentals are not so great. Promoters are frequently paid based on how much they can move a stock's price, but such moves are not long-lasting. They peter out when the trading volumes return to more normal ranges for the stock because all of the hype has died out. There are some small-cap NASDAQ stocks which can be susceptible to promotion for the same reason -- they have small floats and/or are thinly traded. Once someone figures out the best targets, they'll accumulate a position and then start posting all kinds of \"\"news\"\" on the web in an effort to drum up interest so they can sell off their position into the buying that follows. The biggest problem with penny/pink sheet stocks is that they frequently fail to publish reliable financial statements, and their ownership is of a dubious nature. In the past, these types of stocks have been targeted by organized crime syndicates, which ran their own \"\"pump and dump\"\" operations as a way to make relatively easy money. This may still be true to some extent today. Be wary of investing in any publicly-traded firm that has to use promoters to drum up investor interest, because it can be a serious red flag. Even if it means missing out on a short-term opportunity, research the company before investing. Read its financials, understand how it has behaved through its trading history, learn about the products/services it is selling. Do your homework. Otherwise you are doing the investing equivalent of taking your money and lighting it on fire. Remember, there's a good reason these companies are trading as penny/pink sheet stocks, and it generally has nothing to do with the notion (the promoters will tell you) that somehow the \"\"market has missed out on this amazing opportunity.\"\" Pump and dump schemes, which lie at the heart of almost all stock promotion, rely on convincing you, the investor, that you're smart enough to see what others haven't. I hope this helps. Good luck!\"",
"title": ""
},
{
"docid": "510163",
"text": "\"The Minnesota Mining and Manufacturing Company was established in 1902 as a private company. It first raised public funds around 1903 but had a limited shareholder base. By around 1929, it was reported as being tradeable as an OTC (over-the-counter) stock but it's likely that shares were traded well before this. On 14 Jan 1946, the stock was listed on NYSE. On 26 Sep 1962 it became a constituent of the the S&P 500 index. On 9 Aug 1976 it became a constituent of the Dow Jones Industrial Average. In 2002, the company's name changed to 3M Co. It appears that the data on Crunchbase's \"\"IPO Date\"\" is wrong on this one. However, there are several companies that appear to do an \"\"IPO\"\" and have trading prices prior. This is quite typical of early-stage biotech companies that trade OTC prior to a major exchange listing and \"\"IPO\"\". An example of an IPO happening after a company became publicly tradeable is NASDAQ:IMRN (Immuron). They had an \"\"IPO\"\" on Nasdaq on 9 Jun 2017, yet they had been trading as an OTC/Pink Sheet stock for months prior. They also have been listed in Australia since 30 Apr 1999. http://www.nasdaq.com/markets/ipos/activity.aspx?tab=pricings&month=2017-06 Another example is NASDAQ:GNTY (Guaranty Banchshares Inc) which had an \"\"IPO\"\" and NASDAQ listing in May 2017. This was a Nasdaq stock in 1998, went OTC/pink sheet stock in 2005. It has been paying regular dividends since that time. Clearly the word \"\"Initial\"\" is subjective! http://www.nasdaq.com/markets/ipos/activity.aspx?tab=pricings&month=2017-05\"",
"title": ""
},
{
"docid": "165973",
"text": "It depends on what site you're looking on and what exchange they're pulling the data from. Even though funds and stocks are called the same thing, they have different ticker symbols in each country's exchange or could be traded as pink sheet stocks in the US. If a company or fund is based in another country (like Canada or the UK) they probably also trade on that country's exchange (Toronto or London) under a different symbol. This can cause a lot of confusion when researching these tickers.",
"title": ""
},
{
"docid": "253847",
"text": "While most all Canadian brokers allow us access to all the US stocks, the reverse is not true. But some US brokers DO allow trading on foreign exchanges. (e.g. Interactive Brokers at which I have an account). You have to look and be prepared to switch brokers. Americans cannot use Canadian brokers (and vice versa). Trading of shares happens where-ever two people get together - hence the pink sheets. These work well for Americans who want to buy-sell foreign stocks using USD without the hassle of FX conversions. You get the same economic exposure as if the actual stock were bought. But the exchanges are barely policed, and liquidity can dry up, and FX moves are not necessarily arbitraged away by 'the market'. You don't have the same safety as ADRs because there is no bank holding any stash of 'actual' stocks to backstop those traded on the pink sheets.",
"title": ""
},
{
"docid": "291903",
"text": "\"Pink Sheets is not a stock exchange per se, and securities traded through it are not as \"\"safe\"\" as the ones on a stock exchange regulated by SEC. Many companies are traded there because they failed to comply with the SEC regulations, or are bankrupt or don't want the level of reporting to the public that the SEC regulations require. Since you're talking about an ADR of a company traded on LSE, it might be much safer that other, \"\"regular\"\", securities, but still it means that you're buying an unregulated security (even if it is of a company regulated elsewhere). Notice the volume of trades: mere thousands of dollars per day (in a good day, in some days there are no trades at all). It makes it harder to sell the security when needed. Why not buying at LSE?\"",
"title": ""
},
{
"docid": "54257",
"text": "\"If you own 1% of a company, you are technically entitled to 1% of the current value and future profits of that company. However, you cannot, as you seem to imply, just decide at some point to take your ball and go home. You cannot call up the company and ask for 1% of their assets to be liquidated and given to you in cash. What the 1% stake in the company actually entitles you to is: 1% of total shareholder voting rights. Your \"\"aye\"\" or \"\"nay\"\" carries the weight of 1% of the total shareholder voting block. Doesn't sound like much, but when the average little guy has on the order of ten-millionths of a percentage point ownership of any big corporation, your one vote carries more weight than those of millions of single-share investors. 1% of future dividend payments made to shareholders. For every dollar the corporation makes in profits, and doesn't retain for future growth, you get a penny. Again, doesn't sound like much, but consider that the Simon property group, ranked #497 on the Fortune 500 list of the world's biggest companies by revenue, made $1.4 billion in profits last year. 1% of that, if the company divvied it all up, is $14 million. If you bought your 1% stake in March of 2009, you would have paid a paltry $83 million, and be earning roughly 16% on your initial investment annually just in dividends (to say nothing of the roughly 450% increase in stock price since that time, making the value of your holdings roughly $460 million; that does reduce your actual dividend yield to about 3% of holdings value). If this doesn't sound appealing, and you want out, you would sell your 1% stake. The price you would get for this total stake may or may not be 1% of the company's book value. This is for many reasons: Now, to answer your hypothetical: If Apple's stock, tomorrow, went from $420b market cap to zero, that would mean that the market unanimously thought, when they woke up tomorrow morning, that the company was all of a sudden absolutely worthless. In order to have this unanimous consent, the market must be thoroughly convinced, by looking at SEC filings of assets, liabilities and profits, listening to executive statements, etc that an investor wouldn't see even one penny returned of any cash investment made in this company's stock. That's impossible; the price of a share is based on what someone will pay to have it (or accept to be rid of it). Nobody ever just gives stock away for free on the trading floor, so even if they're selling 10 shares for a penny, they're selling it, and so the stock has a value ($0.001/share). We can say, however, that a fall to \"\"effectively zero\"\" is possible, because they've happened. Enron, for instance, lost half its share value in just one week in mid-October as the scope of the accounting scandal started becoming evident. That was just the steepest part of an 18-month fall from $90/share in August '00, to just $0.12/share as of its bankruptcy filing in Dec '01; a 99.87% loss of value. Now, this is an extreme example, but it illustrates what would be necessary to get a stock to go all the way to zero (if indeed it ever really could). Enron's stock wasn't delisted until a month and a half after Enron's bankruptcy filing, it was done based on NYSE listing rules (the stock had been trading at less than a dollar for 30 days), and was still traded \"\"over the counter\"\" on the Pink Sheets after that point. Enron didn't divest all its assets until 2006, and the company still exists (though its mission is now to sue other companies that had a hand in the fraud, get the money and turn it around to Enron creditors). I don't know when it stopped becoming a publicly-traded company (if indeed it ever did), but as I said, there is always someone willing to buy a bunch of really cheap shares to try and game the market (buying shares reduces the number available for sale, reducing supply, increasing price, making the investor a lot of money assuming he can offload them quickly enough).\"",
"title": ""
},
{
"docid": "454465",
"text": "If you are trying to invest in closely held / private companies (things that don't trade on the stock market), you will run into a variety of regulatory problems. For various reasons, most private companies only raise funds with accredited investors. To be an accredited investor you basically have to have $1,000,000 in net worth - NOT including your primary residence, OR you have to make over $200,000 a year for the last two years and expect to keep making that much. This is a class distinction the Federal government created, you will see different but similar wealth and investment classes worldwide. So your best most organized opportunities are left out, unless you do qualify as an accredited investor. There are tons of other companies, things you will find locally, that will let you invest in their smaller time operations. (Think like a local yoga studio looking for $20,000 and willing to split the profits with you). But the problem here is lack of accountability, where partners skip town or just stop answering your calls, and the legal remedies cost you more than your claim. That being said there are people that provide capital to smaller publicly traded companies on the bulletin boards and pink sheets. They have opportunities do much better than the actual stock market investors in these companies, because you can negotiate contracts that let you cash out in their inevitable financing death spirals with very little risk to you. You can do these things as an individual or as a holding company, but the holding company will limit your liability to the amount your holding company invested, instead of your personal assets, in case your financing starts to incur liability with the company.",
"title": ""
},
{
"docid": "404936",
"text": "Depends on the structure of the company and what shares are outstanding. If the pink sheet stock has no voting power then buying all that stock doesn't get you any control at all. On the other hand, if the outstanding shares only represent 20% of the company's overall shares, then buying all the shares isn't likely enough to have a controlling interest. Thus, you'll have to dig into the details. If you want an example of where I'd have my doubts, look at Nestle's stock which has the ticker of NSRGY. There can be companies that are structured with stock on multiple exchanges that can also be a challenge at times. There is also something to be said if you own enough stock in a company that this has to be disclosed to the SEC when you buy more.",
"title": ""
},
{
"docid": "319599",
"text": "Well I'm not going to advise whether it's a good idea to invest in this company (though often OTC is pretty scary), but it DOES have a product (vivio, an ad blocker), it did post financials and it's trading on the OTC-QB (which is better than the pink sheets), so you need to look these over and study up on the product to decide if it is overpriced or not. What might have occurred (viz the Patriot Berry Farm becoming Cyberfort) is that the latter bought up the stock of the former (this is, I believe, called using a shell, which is not necessarily a bad thing) and is using this as a way to be registered, i.e. sell to non-accredited investors via the OTC market. So I'm really just answering your third question: yes, you have to do a lot of due diligence to see if buying this stock is a good deal or not. It might be the next big thing. Or it might not. It certainly is the case that low trading volume allows a relatively small trade to really change the stock price, so the penny stocks do tend to be easier to 'inflate'. Side comment: the bid/ask spreads are pretty big, with a best bid of 0.35 and best ask of 0.44.",
"title": ""
},
{
"docid": "110584",
"text": "For the lazy, Wikipedia says: The term microcap stock (also micro-cap) refers to the stock of public companies in the United States which have a market capitalization of roughly $300 million or less. The shares of companies with a market capitalization of less than $50 million are typically referred to as nano-cap stocks. Many micro-cap and nano-cap stocks are traded over-the-counter with their prices quoted on the OTCBB or the Pink Sheets. A few of the larger, more established microcaps are listed on the NASDAQ Capital Market or American Stock Exchange (AMEX). Micro-cap and especially nano-cap stocks are notorious for their volatility. A high percentage of these companies fail to execute their business plans and go out of business. Fraud and market manipulation are not uncommon, and the transactions costs in trading can be quite high. Pricing is more likely to be inefficient, since fewer institutional investors and analysts operate in this space, due to the relatively small dollar amounts involved and the lack of liquidity.",
"title": ""
},
{
"docid": "495255",
"text": "I'd call it pretty worrisome. HOOB is trading over the counter, in fact, on the pink sheets, so it has been delisted from the major exchanges. It appears that it lacks recent financial disclosures. You'll have to investigate to see if you think it's worth keeping, but trading is thin.",
"title": ""
},
{
"docid": "555047",
"text": "I traded futures for a brief period in school using the BrokersXpress platform (now part of OptionsXpress, which is in turn now part of Charles Schwab). They had a virtual trading platform, and apparently still do, and it was excellent. Since my main account was enabled for futures, this carried over to the virtual account, so I could trade a whole range of futures, options, stocks, etc. I spoke with OptionsXpress, and you don't need to fund your acount to use the virtual trading platform. However, they will cancel your account after an arbitrary period of time if you don't log in every few days. According to their customer service, there is no inactivity fee on your main account if you don't fund it and make no trades. I also used Stock-Trak for a class and despite finding the occasional bug or website performance issue, it provided a good experience. I received a discount because I used it through an educational institution, and customer service was quite good (probably for the same reason), but I don't know if those same benefits would apply to an individual signing up for it. I signed up for top10traders about seven years ago when I was in secondary school, and it's completely free. Unfortunately, you get what you pay for, and the interface was poorly designed and slow. Furthermore, at that time, there were no restrictions that limited the number of shares you could buy to the number of outstanding shares, so you could buy as many as you could afford, even if you exceeded the number that physically existed. While this isn't an issue for large companies, it meant you could earn a killing trading highly illiquid pink sheet stocks because you could purchase billions of shares of companies with only a few thousand shares actually outstanding. I don't know if these issues have been corrected or not, but at the time, I and several other users took advantage of these oversights to rack up hundreds of trillions of dollars in a matter of days, so if you want a realistic simulation, this isn't it. Investopedia also has a stock simulator that I've heard positive things about, although I haven't used it personally.",
"title": ""
},
{
"docid": "390779",
"text": "\"The assumption that companies listed OTC are not serious is far from the truth. Many companies on the OTC are just starting off there because they don't meet the requirements to be listed on the NASDAQ or NYSE. Major stock exchanges like the NASDAQ and the NYSE only want the best companies to trade on their exchanges.The NASDAQ, for example, has three sets of listing requirements. A company must meet at least one of the three requirement sets, as well as the main rules for all companies. These include: Now don't assume that the OTC doesn't have rules either, as this is far from the truth as well. While there are no minimum level of revenue, profits or assets required to get listed on the OTC there are requirements for audited financial statements and ongoing filing and reporting to the SEC and NASD. Additionally there are several different levels of the OTC, including the OTCQX, the OTCCB and the OTC Pink, each with their own set of requirements. For more information about what it takes to be listed on OTC look here: http://www.otcmarkets.com/learn/otc-trading A company deciding to trade on the OTC is making the decision to take their company public, and they are investing to make it happen. Currently the fees to get listed on the OTC range from $30,000 to $150,000 depending on the firm you decide to go with and the services they offer as part as their package. Now, I know I wouldn't consider $30K (or more) to not be serious money! When I looked into the process of getting a company listed on the TSX the requirements seemed a lot more relaxed than those of the major U.S. markets as well, consisting of an application, records submission and then a decision made by a TSX committee about whether you get listed. More information about the TSX here: http://apps.tmx.com/en/listings/listing_with_us/process/index.html I think the way that the OTC markets have gotten such a bad reputation is from these \"\"Get Rich on Penny Stock\"\" companies that you see pumping up OTC company stocks and getting massive amounts of people to buy without doing their due diligence and investigating the company and reading its prospectus. Then when they loose a bunch of money on an ill-informed investment decision they blame it on the company being an OTC stock. Whether you decide to trade the OTC market or not, I wouldn't make a decision based on how many exchanges the company is listed on, but rather based on the research you do into the company.\"",
"title": ""
},
{
"docid": "129481",
"text": "I'm going to guess that you found this because of a stock screener. This company went through a 1:20 reverse split on June 30, so every 20 shares outstanding became a single share. Where before you had 20 shares worth $100 you now have 1 share worth $100, the value of the company doesn't change because of a split. This company was never trading for $30+ per share. Reverse splits are typical of a floundering company trading on an exchange that has a minimum share price requirement. While reverse splits don't change the value of the company, just the number of shares outstanding and the price per share, no healthy company performs a reverse split. Reverse splits are generally a massive signal to jump ship... The company seems to be trading for $1 right now, why the value fell from a pre-split $1.65 ($33/20) to $1 is anyone's guess; how the company ever got to $1.65 is also anyone's guess. But looking at the most recent 10-Q there are numerous causes for concern: Note 2. Capital Stock On March 6, 2017, the Company issued as compensation for services provided a total of 650,000 common shares with a fair value of $390,000 to a third party. The fair value of the shares was based on the price quoted on the OTC pink sheets on the grant date. this indicates a share price of $0.60 ($390,000/650,000) as of 3/6/2017, just to reinforce that the google price chart doesn't show the true past but a past adjusted for the split Results of Operations The three months ended March 31, 2017 compared to the three months ended March 31, 2016 For the three months ended March 31, 2017 compared to the three months ended March 31, 2016, total revenues were $0 and $0, respectively, and net losses from operations were $414,663 and $26,260, respectively. The net losses were attributable to costs attributable to operating as a public company, in particular, common stock with a valuation of $390,000 that was issued to an investor relations firm in the first quarter of 2017. Going Concern As of March 31, 2017, there is substantial doubt regarding our ability to continue as a going concern as we have not generated sufficient cash flow to fund our proposed business. We have suffered recurring losses from operations since our inception. In addition, we have yet to generate an internal cash flow from our business operations or successfully raised the financing required to develop our proposed business. As a result of these and other factors, our independent auditor has expressed substantial doubt about our ability to continue as a going concern. Liquidity and Capital Resources We had no cash as of the date of March 31, 2017. Additionally, since there is no balance sheet in the last 10-Q (another bad sign), the last annual report 10-K has this balance sheet: So the company: So why did the stock value plummet? It's anyones' guess but there is no shortage of ways to justify it. In fact, it's reasonable to ask how is this company still worth $3mm ($1 * 3mm shares outstanding)...",
"title": ""
},
{
"docid": "151871",
"text": "\"Their is no arbitrage opportunity with \"\"buying dividends.\"\" You're buying a taxable event. This is a largely misunderstood topic. The stock always drops by the amount if the dividend on the ex date. The stock opens that day trading \"\"ex\"\" (excluding) the dividend. It then pays out later based in the shareholders on record. There is a lot of talk about price movement and value here. That can happen but it's from trading not from the dividend per se. Yes sometimes you do see a stock pop the day prior to ex date because people are buying the stock for the dividend but the trading aspect of a stock is determined by supply and demand from people trading the stock. The dividends are paid out from the owners equity section of the balance sheet. This is a return of equity to shareholders. The idea is to give owners of the company some of their investment back (from when they bought the stock) without having the owners sell the shares of the company. After all if it's a good company you want to keep holding it so it will appreciate. Another similar way to think of it is like a bonds interest payment. People sometimes forget when trading that these are actual companies meant to be invested in. Your buying an ownership in the company with your cash. It really makes no difference to buy the dividend or not, all other things constant. Though market activity can add or lose value from trading as normal.\"",
"title": ""
},
{
"docid": "506460",
"text": "First, I want to point out that your question contains an assumption. Does anyone make significant money trading low volume stocks? I'm not sure this is the case - I've never heard of a hedge fund trading in the pink sheets, for example. Second, if your assumption is valid, here are a few ideas how it might work: Accumulate slowly, exit slowly. This won't work for short-term swings, but if you feel like a low-volume stock will be a longer-term winner, you can accumulate a sizable portion in small enough chunks not to swing the price (and then slowly unwind your position when the price has increased sufficiently). Create additional buyers/sellers. Your frustration may be one of the reasons low-volume stock is so full of scammers pumping and dumping (read any investing message board to see examples of this). If you can scare holders of the stock into selling, you can buy significant portions without driving the stock price up. Similarly, if you can convince people to buy the stock, you can unload without destroying the price. This is (of course) morally and legally dubious, so I would not recommend this practice.",
"title": ""
},
{
"docid": "160421",
"text": "When I read that part of his post, it reminded me more of credit companies rather than banks. People default on credit all the time. I have no idea what the regulations are on the amount of credit that a company can issue, though. And this is sort of part of what actually happened in the beginning of the economic crunch. A bunch of people began to trade for credit (debt) against what they thought the *future* value of their house or other real estate would be. After a while, people stopped being able to afford property at its future value, so they stopped buying it. When people then tried to sell their property for the future value that they had borrowed against, they couldn't, so they couldn't pay back their debt. Because real estate had become a popular investment vehicle for the middle class, this was able to reach a kind of critical mass, and shortly afterward the effects rippled back into the credit market, which also had its own crunch -- a bunch of credit just disappeared overnight because so many people had assumed a level of debt that they could not actually fulfill their promises on once the future value of their home became completely imaginary.",
"title": ""
},
{
"docid": "365465",
"text": "\"Very simple. You open an account with a broker who will do the trades for you. Then you give the broker orders to buy and sell (and the money to pay for the purchases). That's it. In the old days, you would call on the phone (remember, in all the movies, \"\"Sell, sell!!!!\"\"? That's how), now every decent broker has an online trading platform. If you don't want to have \"\"additional value\"\" and just trade - there are many online discount brokers (ETrade, ScotTrade, TD Ameritrade, and others) who offer pretty cheap trades and provide decent services and access to information. For more fees, you can also get advices and professional management where an investment manager will make the decisions for you (if you have several millions to invest, that is). After you open an account and login, you'll find a big green (usually) button which says \"\"BUY\"\". Stocks are traded on exchanges. For example the NYSE and the NASDAQ are the most common US exchanges (there's another one called \"\"pink sheets\"\", but its a different kind of animal), there are also stock exchanges in Europe (notably London, Frankfurt, Paris, Moscow) and Asia (notably Hong Kong, Shanghai, Tokyo). Many trading platforms (ETrade, that I use, for example) allow investing on some of those as well.\"",
"title": ""
},
{
"docid": "593644",
"text": "NSCC illiquid charges are charges that apply to the trading of low-priced over-the counter (OTC) securities with low volumes. Open net buy quantity represents the total unsettled share amount per stock at any given time during a 3-day settlement cycle. Open net buy quantity must be less than 5,000,000 shares per stock for your entire firm Basically, you can't hold a long position of more than 5 million shares in an illiquid OTC stock without facing a fee. You'll still be assessed this fee if you accumulate a long position of this size by breaking your purchase up into multiple transactions. Open net sell quantity represents the total unsettled share amount per stock at any given time during a 3-day settlement cycle. Open net sell quantity must be less than 10% percent of the 20-day average volume If you attempt to sell a number of shares greater than 10% of the stock's average volume over the last 20 days, you'll also be assessed a fee. The first link I included above is just an example, but it makes the important point: you may still be assessed a fee for trading OTC stocks even if your account doesn't meet the criteria because these restrictions are applied at the level of the clearing firm, not the individual client. This means that if other investors with your broker, or even at another broker that happens to use the same clearing firm, purchase more than 5 million shares in an individual OTC stock at the same time, all of your accounts may face fees, even though individually, you don't exceed the limits. Technically, these fees are assessed to the clearing firm, not the individual investor, but usually the clearing firm will pass the fees along to the broker (and possibly add other charges as well), and the broker will charge a fee to the individual account(s) that triggered the restriction. Also, remember that when buying OTC/pink sheet stocks, your ability to buy or sell is also contingent on finding someone else to buy from/sell to. If you purchase 10,000 shares one day and attempt to sell them sometime in the future, but there aren't enough buyers to buy all 10,000 from you, you might not be able to complete your order at the desired price, or even at all.",
"title": ""
},
{
"docid": "61418",
"text": "\">BPI took such a hard hit because they showed the world that they're the type of company willing to sell people really nasty shit just to make a buck (in my opinion). Honestly, if there was a news expose on 90% of the processed food that is on grocery store shelves, people would have the same reaction. You would be shocked as to what happens in food manufacturing facilities. Yes, there are FDA, USDA, and many other agencies that do both announced and surprise audits of food manufacturers to ensure food safety, but this is just a snapshot in time, and the food is only deemed as safe as to the standards of that company and what the definition of \"\"safe\"\" is. IMO, yes, BPI took a huge hit because of this being called pink slime. Are they manufacturing something that is potentially dangerous for consumption? Possibly. That all depends on who you ask what \"\"safe for consumption\"\" means. Are lobbyists involved? Bet your ass they are. But the market at the time was demanding a type of beef that was super lean. All BPI did was find a way to fulfill that need. I don't know what the outcome of this will be, but I can absolutely see both sides of the argument. The press needs to be free to report on anything and everything. However, there needs to be regulation regarding what they can and can not say from a slander standpoint. Coming up with a cute catch phrase such as \"\"pink slime\"\" is slanderous, and potentially damaging. That's where I agree with you and believe that they should have reported on the factual inclusions in the finished product. /rant\"",
"title": ""
},
{
"docid": "393925",
"text": "Many of the major indices retreated today because of this news. Why? How do the rising budget deficits and debt relate to the stock markets? It does seem strange that there is a correlation between government debt and the stock market. But I could see many reasons for the reaction. The downgrade by S&P may make it more expensive for the government to borrow money (i.e. higher interest rates). This means it becomes more expensive for the government to borrow money and the government will probably need to raise taxes to cover the cost of borrowing. Rising taxes are not good for business. Also, many banks in the US hold US government debt. Rising yields will push down the value of their holdings which in turn will reduce the value of US debt on the businesses' balance sheets. This weakens the banks' balance sheets. They may even start to unload US bonds. Why is there such a large emphasis on the S&P rating? I don't know. I think they have proven they are practically useless. That's just my opinion. Many, though, still think they are a credible ratings agency. What happens when the debt ceiling is reached? Theoretically the government has to stop borrowing money once the debt ceiling is reached. If this occurs and the government does not raise the debt ceiling then the government faces three choices:",
"title": ""
},
{
"docid": "542765",
"text": "Using Fundamental and Technical Analysis together is actually a good idea for longer term trading of up to 6 months or longer. The whole idea behind trading with Technical Analysis is to increase the probabilities of a trade going in the desired direction by using uncorrelated indicators that produce the same signal to buy or sell at the same time. For example, you might use a Moving Average (MA) as a buy signal when the price falls for a few days, hits the MA and then reverses and starts moving back up. If however, you also include a Stochastic Oscillator (SO) to indicate when the stock is oversold (under 20%), and if the price rebounds from the MA average at the same time as the Stochastic is crossing over in the oversold position, then this may be a higher probability trade. If you also only trade stocks that are Fundamentally healthy (as fundamentally good stocks are more likely to go up than fundamentally bad stocks) then this might increase the probabilities again. Then if you only buy when the market as a whole is moving up, then this will increase your chances again. A few weeks ago at a seminar, the presenter totalled the men in the room to be 76 and the women in the room to be 8. He then asked what will most likely be the next person to walk in the room - a man or a woman? The statistics are on the side of a wan walking in next. This is what we try to do with Technical Analysis, increase our chances when we take a trade. Of course a woman could be the next person to walk in the room, just like any trade can go against you, and this is why we use money management and risk management and take a small loss when a trade does go against you. Lets look at an example where you could incorporate FA with TA to increase your chances of profits: Above is a candlestick chart of Select Harvest (SHV), the green line above the price is the perceived value, the pink line is the 40 day MA, the blue line is the EPS, and the white lines is the Stochastic Oscillator (above 80% being overbought and below 20% is oversold). From Feb 2015 to start of Aug 2015 the stock was uptrending, since then the price reversed and started to downtrend. The stock was determined to be fundamentally good early in 2015 with the perceived value gradually increasing and greater than the share price, and the EPS starting to increase regularly from mid April. Thus, as the stock is seen as fundamentally healthy any price reversal in the vicinity of the MA could be seen as a buy opportunity. In fact there where 2 such opportunities on 31st March and 11th June where price had reversed and rebounded off the MA whist the SO crossed over in or near the oversold area. The price did reverse and then rebounded off the MA again on 9th July, however the SO was not in or near the oversold area on this occasion, so not as high in probability terms. The price still rebounded and went up again, however another momentum indicator (not shown here) shows some bearish divergence in this case - so another reason to possibly keep away at this point in time. A good signal to get out of the trade, that is your stop loss has not already taken you out, is when the price breaks and closes below the MA line. This occurred on 7th August. So if we had bought on the first signal on 31st March for $7.41 and sold when the priced broke through the MA on 7th August for $11.76, we would have made a profit of approx. 59% in just over 4 months. If bought on the second signal on 11th June for $9.98 and again sold on 7th August for $11.76, we would have made about 18% in under 2 months. So the fundamentals, the Price (in relation to MA) and the SO where all lining up to provide two high probability trades. Of course you would need to incorporate you risk management (including stops) in case the price did not continue upwards after you bought. If the market is also moving up on the day of the signal this will further increase your chances. Unless you day trade, which I would avoid, a good way to enter your trades after a signal is to enter a stop buy order after market close to buy if the price moves above the high of the signal day. That way if the market and the stock open and move lower during the day after the signal you avoid entering the trade altogether. This can be incorporated as part of your risk management and trading rules. After the price broke down through the MA we can see that a downtrend commenced which is still current today (in fact I just took a short trade on this stock yesterday). We can also see that the perceived value, whilst still above the price, has reached a peak and is currently moving downwards and the EPS after being flat for a few months has just moved down for the first time in 10 months. So maybe the fundamentals are starting to waver a bit on this stock. It may be a good stock to continue shorting into the future. So basically you can continue using Fundamental Analysis to select which stocks to buy, place them in a watch-list, and then use Technical Analysis to determine when these stocks are starting to uptrend and use a combination of uncorrelated indicators to produce higher probability signals for when to enter your trades.",
"title": ""
},
{
"docid": "565971",
"text": ">PI’s attorney, Dan Webb, said in court Monday that ABC used the term “pink slime” 350 times over the course of its reporting, and that ABC willfully spread this preconceived, negative message. Webb also showed the jurors a picture of lean finely textured beef. “It physically doesn’t look like slime,” he said. It physically doesn't look like slime, and presumably it isn't slime chemically. What's their reason for calling it 'pink slime'? >In fact, the term “pink slime” was coined by one of the segment’s whistleblowing USDA scientists in a 2002 email to colleagues, and a 2009 New York Times piece using the term to describe BPI’s meat product won a Pulitzer Prize. So, they coined a word to describe something that was intentionally designed to sensationalize it, in a negative way. If I were on the jury this is the point of fact that I'd base my vote on. The media needs to be slapped pretty hard when they start actively damaging people and companies to sell stories.",
"title": ""
},
{
"docid": "287325",
"text": "\"What could the tax issues with the IRS be? I thought (but not totally certain) that the tax treatment of an ISO option was based on difference between exercise price and FMV at the time of the sale. This is an accounting issue. There were times not so long ago that companies actually did these things on purpose, to boost the stock grant values for their employees (especially senior employees). They would give a grant but date it with an earlier date with a more favorable valuation. This is called \"\"backdating\"\", and it brought companies down and CEOs into criminal courts. In addition, only reasonable compensation is allowed as a deduction for the company, and incorrectly set strike price may be deemed unreasonable. Thus, the deduction the company would take for your compensation can be denied, leading to loss of tax benefit (this was also a weapon used by the IRS at the time against companies doing backdating). Last but not least, company that has intentions of going public cannot allow itself such a blatant disregard of the accounting rules. Even if the mistake was not made on purpose (as it sounds), it is a mistake that has to be corrected. What should I take into consideration to determine whether a 27% increase in shares is a fair exchange for an increase in 270% increase in strike price. Did you know the strike price when you signed the contract? Was it a consideration for you? For most people, the strike price is determined at the board approval, since the valuations are not public and are not disclosed before you actually join, which is already after you've agreed to the terms. So basically, you agreed to get 100 sheets of toilet paper, and instead getting 127 sheets. So you're getting 27 sheets more than you initially agreed to. Why are you complaining? In other words, options are essentially random numbers which are quite useless. By the time you get to exercise them, they'll be diluted through a bunch of additional financing rounds, and their value will be determined for real only after the IPO, or at least when your company's stocks are trading OTC with some reasonable volume. Until then - it's just a number with not much of a meaning. The FMV does matter for early exercise and 83(b) election, if that is an option, but even then - I doubt you can actually negotiate anything.\"",
"title": ""
},
{
"docid": "316673",
"text": "We constantly hear that there are not enough trades-people to fill manufacturing roles. This is what happens when you offshore everything possible for the last 30 years. No one wants to go into a trade that will be offshored plus there are too few of those positions to apprentice in. Stop the boo-hooing big business, man-up and invest in some of your fellow citizens.",
"title": ""
},
{
"docid": "312811",
"text": "\"Share sales & purchases are accounted only on the balance sheet & cash flow statement although their effects are seen on the income statement. Remember, the balance sheet is like a snapshot in time of all accrued accounts; it's like looking at a glass of water and noting the level. The cash flow and income statements are like looking at the amount of water, \"\"actually\"\" and \"\"imaginary\"\" respectively, pumped in and out of the glass. So, when a corporation starts, it sells shares to whomever. The amount of cash received is accounted for in the investing section of the cash flow statement under the subheading \"\"issuance (retirement) of stock\"\" or the like, so when shares are sold, it is \"\"issuance\"\"; when a company buys back their shares, it's called \"\"retirement\"\", as cash inflows and outflows respectively. If you had a balance sheet before the shares were sold, you'd see under the \"\"equity\"\" heading a subheading common stock with a nominal (irrelevant) par value (this is usually something obnoxiously low like $0.01 per share used for ease of counting the shares from the Dollar amount in the account) under the subaccount almost always called \"\"common stock\"\". If you looked at the balance sheet after the sale, you'd see the number of shares in a note to the side. When shares trade publicly, the corporation usually has very little to do with it unless if they are selling or buying new shares under whatever label such as IPO, secondary offering, share repurchase, etc, but the corporation's volume from such activity would still be far below the activity of the third parties: shares are trading almost exclusively between third parties. These share sales and purchases will only be seen on the income statement under earnings per share (EPS), as EPS will rise and fall with stock repurchases and sales assuming income is held constant. While not technically part of the income statement but printed with it, the \"\"basic weighted average\"\" and \"\"diluted weighted average\"\" number of shares are also printed which are the weighted average over the reporting period of shares actually issued and expected if all promises to issue shares with employee stock options, grants, convertibles were made kept. The income statement is the accrual accounts of the operations of the company. It has little detail on investing (depreciation & appreciation) or financing (interest expenses & preferred dividends).\"",
"title": ""
},
{
"docid": "407274",
"text": "There are lots of good points here already, but something that hasn't been mentioned yet is what would happen if the purchased items break or are somehow defective? Depending on the warranty and how trustworthy the company is, there could be an advantage to not having fully paid for the item yet when a defect is discovered, as it might incentivize the company to be more attentive to your warranty claim, since they are faced with knowing that you could stop making payments if they don't act in a timely manner. Note I'm not suggesting you stop making payments in this case, just that companies (and banks) are oftentimes more willing to work with you when you owe them money.",
"title": ""
},
{
"docid": "301547",
"text": "\"To my knowledge, there's no universal equation, so this could vary by individual/company. The equation I use (outside of sentiment measurement) is the below - which carries its own risks: This equations assumes two key points: Anything over 1.2 is considered oversold if those two conditions apply. The reason for the bear market is that that's the time stocks generally go on \"\"sale\"\" and if a company has a solid balance sheet, even in a downturn, while their profit may decrease some, a value over 1.2 could indicate the company is oversold. An example of this is Warren Buffett's investment in Wells Fargo in 2009 (around March) when WFC hit approximately 7-9 a share. Although the banking world was experiencing a crisis, Buffett saw that WFC still had a solid balance sheet, even with a decrease in profit. The missing logic with many investors was a decrease in profits - if you look at the per capita income figures, Americans lost some income, but not near enough to justify the stock falling 50%+ from its high when evaluating its business and balance sheet. The market quickly caught this too - within two months, WFC was almost at $30 a share. As an interesting side note on this, WFC now pays $1.20 dividend a year. A person who bought it at $7 a share is receiving a yield of 17%+ on their $7 a share investment. Still, this equation is not without its risks. A company may have a solid balance sheet, but end up borrowing more money while losing a ton of profit, which the investor finds out about ad-hoc (seen this happen several times). Suddenly, what \"\"appeared\"\" to be a good sale, turns into a person buying a penny with a dollar. This is why, to my knowledge, no universal equation applies, as if one did exist, every hedge fund, mutual fund, etc would be using it. One final note: with robotraders becoming more common, I'm not sure we'll see this type of opportunity again. 2009 offered some great deals, but a robotrader could easily be built with the above equation (or a similar one), meaning that as soon as we had that type of environment, all stocks fitting that scenario would be bought, pushing up their PEs. Some companies might be willing to take an \"\"all risk\"\" if they assess that this equation works for more than n% of companies (especially if that n% returns an m% that outweighs the loss). The only advantage that a small investor might have is that these large companies with robotraders are over-leveraged in bad investments and with a decline, they can't make the good investments until its too late. Remember, the equation ultimately assumes a person/company has free cash to use it (this was also a problem for many large investment firms in 2009 - they were over-leveraged in bad debt).\"",
"title": ""
}
] |
896
|
Overexpressing Cnp1 N-tail variants exacerbates the temperature-sensitive growth defect of scm3-139.
|
[
{
"docid": "14338915",
"text": "The mechanisms ensuring specific incorporation of CENP-A at centromeres are poorly understood. Mis16 and Mis18 are required for CENP-A localization at centromeres and form a complex that is conserved from fission yeast to human. Fission yeast sim1 mutants that alleviate kinetochore domain silencing are defective in Scm3(Sp), the ortholog of budding yeast Scm3(Sc). Scm3(Sp) depends on Mis16/18 for its centromere localization and like them is recruited to centromeres in late anaphase. Importantly, Scm3(Sp) coaffinity purifies with CENP-A(Cnp1) and associates with CENP-A(Cnp1) in vitro, yet localizes independently of intact CENP-A(Cnp1) chromatin and is differentially released from chromatin. While Scm3(Sc) has been proposed to form a unique hexameric nucleosome with CENP-A(Cse4) and histone H4 at budding yeast point centromeres, we favor a model in which Scm3(Sp) acts as a CENP-A(Cnp1) receptor/assembly factor, cooperating with Mis16 and Mis18 to receive CENP-A(Cnp1) from the Sim3 escort and mediate assembly of CENP-A(Cnp1) into subkinetochore chromatin.",
"title": "Fission Yeast Scm3: A CENP-A Receptor Required for Integrity of Subkinetochore Chromatin"
}
] |
[
{
"docid": "10189634",
"text": "CENP-A chromatin forms the foundation for kinetochore assembly. Replication-independent incorporation of CENP-A at centromeres depends on its chaperone HJURP(Scm3), and Mis18 in vertebrates and fission yeast. The recruitment of Mis18 and HJURP(Scm3) to centromeres is cell cycle regulated. Vertebrate Mis18 associates with Mis18BP1(KNL2), which is critical for the recruitment of Mis18 and HJURP(Scm3). We identify two novel fission yeast Mis18-interacting proteins (Eic1 and Eic2), components of the Mis18 complex. Eic1 is essential to maintain Cnp1(CENP-A) at centromeres and is crucial for kinetochore integrity; Eic2 is dispensable. Eic1 also associates with Fta7(CENP-Q/Okp1), Cnl2(Nkp2) and Mal2(CENP-O/Mcm21), components of the constitutive CCAN/Mis6/Ctf19 complex. No Mis18BP1(KNL2) orthologue has been identified in fission yeast, consequently it remains unknown how the key Cnp1(CENP-A) loading factor Mis18 is recruited. Our findings suggest that Eic1 serves a function analogous to that of Mis18BP1(KNL2), thus representing the functional counterpart of Mis18BP1(KNL2) in fission yeast that connects with a module within the CCAN/Mis6/Ctf19 complex to allow the temporally regulated recruitment of the Mis18/Scm3(HJURP) Cnp1(CENP-A) loading factors. The novel interactions identified between CENP-A loading factors and the CCAN/Mis6/Ctf19 complex are likely to also contribute to CENP-A maintenance in other organisms.",
"title": "Eic1 links Mis18 with the CCAN/Mis6/Ctf19 complex to promote CENP-A assembly"
},
{
"docid": "16686383",
"text": "The centromeric histone H3 variant (CenH3) is essential for chromosome segregation in eukaryotes. We identify posttranslational modifications of Saccharomyces cerevisiae CenH3, Cse4. Functional characterization of cse4 phosphorylation mutants shows growth and chromosome segregation defects when combined with kinetochore mutants okp1 and ame1. Using a phosphoserine-specific antibody, we show that the association of phosphorylated Cse4 with centromeres increases in response to defective microtubule attachment or reduced cohesion. We determine that evolutionarily conserved Ipl1/Aurora B contributes to phosphorylation of Cse4, as levels of phosphorylated Cse4 are reduced at centromeres in ipl1 strains in vivo, and in vitro assays show phosphorylation of Cse4 by Ipl1. Consistent with these results, we observe that a phosphomimetic cse4-4SD mutant suppresses the temperature-sensitive growth of ipl1-2 and Ipl1 substrate mutants dam1 spc34 and ndc80, which are defective for chromosome biorientation. Furthermore, cell biology approaches using a green fluorescent protein-labeled chromosome show that cse4-4SD suppresses chromosome segregation defects in dam1 spc34 strains. On the basis of these results, we propose that phosphorylation of Cse4 destabilizes defective kinetochores to promote biorientation and ensure faithful chromosome segregation. Taken together, our results provide a detailed analysis, in vivo and in vitro, of Cse4 phosphorylation and its role in promoting faithful chromosome segregation.",
"title": "Phosphorylation of centromeric histone H3 variant regulates chromosome segregation in Saccharomyces cerevisiae"
},
{
"docid": "21425864",
"text": "Glycosyl phosphatidylinositols (GPIs) anchor many proteins to the surface of eukaryotic cells and may also serve as sorting signals on proteins and participate in signal transduction. We have isolated a Saccharomyces cerevisiae GPI anchoring mutant, gpi1, using a colony screen for cells blocked in [3H]inositol incorporation into protein. The gpi1 mutant is defective in vitro in the synthesis of N-acetylglucosaminyl phosphatidylinositol, the first intermediate in GPI synthesis, and is also temperature-sensitive for growth. Completion of the first step in GPI assembly is therefore required for growth of the unicellular eukaryote S. cerevisiae. GPI synthesis could therefore be exploited as a target for antifungal or antiparasitic agents.",
"title": "A conditionally lethal yeast mutant blocked at the first step in glycosyl phosphatidylinositol anchor synthesis."
},
{
"docid": "26117607",
"text": "Down syndrome cell adhesion molecule (Dscam) seems likely to play a key role in the \"alternative adaptive immunity\" that has been reported in invertebrates. Dscam consists of a cytoplasmic tail that is involved in signal transduction and a hypervariable extracellular region that might use a pathogen recognition mechanism similar to that used by the vertebrate antibodies. In our previous paper, we isolated a unique tail-less form of Dscam from Litopenaeus vannamei. In this study, we report the first membrane-bound form of shrimp Dscam: PmDscam was isolated from Penaeus monodon, and it occurred in both membrane-bound and tail-less forms. Phylogenetic analysis showed that while the crustacean Dscams from shrimp and water flea did not share a single subclade, they were distinct from the invertebrate Dscam-like molecules and from the insecta Dscams. In the extracellular region, the variable regions of PmDscam were located in N-terminal Ig2, N-terminal Ig3 and the entire Ig7 domain. The PmDscam extracellular variants and transmembrane domain variants were produced by mutually exclusive alternative splicing events. The cytoplasmic tail variants were produced by exon inclusion/exclusion. Based on the genomic organization of Daphnia Dscam's cytoplasmic tail, we propose a model of how the shrimp Dscam genomic locus might use Type III polyadenylation to generate both the tail-less and membrane-bound forms.",
"title": "Penaeus monodon Dscam (PmDscam) has a highly diverse cytoplasmic tail and is the first membrane-bound shrimp Dscam to be reported."
},
{
"docid": "17671145",
"text": "The androgen receptor (AR) is overexpressed and hyperactivated in human castration-resistant prostate cancer (CRPC). However, the determinants of AR overexpression in CRPC are poorly defined. Here we show that retinoic acid receptor-related orphan receptor γ (ROR-γ) is overexpressed and amplified in metastatic CRPC tumors, and that ROR-γ drives AR expression in the tumors. ROR-γ recruits nuclear receptor coactivator 1 and 3 (NCOA1 and NCOA3, also known as SRC-1 and SRC-3) to an AR-ROR response element (RORE) to stimulate AR gene transcription. ROR-γ antagonists suppress the expression of both AR and its variant AR-V7 in prostate cancer (PCa) cell lines and tumors. ROR-γ antagonists also markedly diminish genome-wide AR binding, H3K27ac abundance and expression of the AR target gene network. Finally, ROR-γ antagonists suppressed tumor growth in multiple AR-expressing, but not AR-negative, xenograft PCa models, and they effectively sensitized CRPC tumors to enzalutamide, without overt toxicity, in mice. Taken together, these results establish ROR-γ as a key player in CRPC by acting upstream of AR and as a potential therapeutic target for advanced PCa.",
"title": "ROR-γ drives androgen receptor expression and represents a therapeutic target in castration-resistant prostate cancer"
},
{
"docid": "4312169",
"text": "Glioblastoma multiforme (GBM) is a lethal brain tumour in adults and children. However, DNA copy number and gene expression signatures indicate differences between adult and paediatric cases. To explore the genetic events underlying this distinction, we sequenced the exomes of 48 paediatric GBM samples. Somatic mutations in the H3.3-ATRX-DAXX chromatin remodelling pathway were identified in 44% of tumours (21/48). Recurrent mutations in H3F3A, which encodes the replication-independent histone 3 variant H3.3, were observed in 31% of tumours, and led to amino acid substitutions at two critical positions within the histone tail (K27M, G34R/G34V) involved in key regulatory post-translational modifications. Mutations in ATRX (α-thalassaemia/mental retardation syndrome X-linked) and DAXX (death-domain associated protein), encoding two subunits of a chromatin remodelling complex required for H3.3 incorporation at pericentric heterochromatin and telomeres, were identified in 31% of samples overall, and in 100% of tumours harbouring a G34R or G34V H3.3 mutation. Somatic TP53 mutations were identified in 54% of all cases, and in 86% of samples with H3F3A and/or ATRX mutations. Screening of a large cohort of gliomas of various grades and histologies (n = 784) showed H3F3A mutations to be specific to GBM and highly prevalent in children and young adults. Furthermore, the presence of H3F3A/ATRX-DAXX/TP53 mutations was strongly associated with alternative lengthening of telomeres and specific gene expression profiles. This is, to our knowledge, the first report to highlight recurrent mutations in a regulatory histone in humans, and our data suggest that defects of the chromatin architecture underlie paediatric and young adult GBM pathogenesis.",
"title": "Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma"
},
{
"docid": "13293033",
"text": "Down syndrome (DS) is the most frequent cause of human congenital mental retardation. Cognitive deficits in DS result from perturbations of normal cellular processes both during development and in adult tissues, but the mechanisms underlying DS etiology remain poorly understood. To assess the ability of induced pluripotent stem cells (iPSCs) to model DS phenotypes, as a prototypical complex human disease, we generated bona fide DS and wild-type (WT) nonviral iPSCs by episomal reprogramming. DS iPSCs selectively overexpressed chromosome 21 genes, consistent with gene dosage, which was associated with deregulation of thousands of genes throughout the genome. DS and WT iPSCs were neurally converted at >95% efficiency and had remarkably similar lineage potency, differentiation kinetics, proliferation, and axon extension at early time points. However, at later time points DS cultures showed a twofold bias toward glial lineages. Moreover, DS neural cultures were up to two times more sensitive to oxidative stress-induced apoptosis, and this could be prevented by the antioxidant N-acetylcysteine. Our results reveal a striking complexity in the genetic alterations caused by trisomy 21 that are likely to underlie DS developmental phenotypes, and indicate a central role for defective early glial development in establishing developmental defects in DS brains. Furthermore, oxidative stress sensitivity is likely to contribute to the accelerated neurodegeneration seen in DS, and we provide proof of concept for screening corrective therapeutics using DS iPSCs and their derivatives. Nonviral DS iPSCs can therefore model features of complex human disease in vitro and provide a renewable and ethically unencumbered discovery platform.",
"title": "Integration-free induced pluripotent stem cells model genetic and neural developmental features of down syndrome etiology."
},
{
"docid": "26625002",
"text": "The outer membrane channel TolC is a key component of multidrug efflux and type I secretion transporters in Escherichia coli. Mutational inactivation of TolC renders cells highly susceptible to antibiotics and leads to defects in secretion of protein toxins. Despite impairment of various transport functions, no growth defects were reported in cells lacking TolC. Unexpectedly, we found that the loss of TolC notably impairs cell division and growth in minimal glucose medium. The TolC-dependent phenotype was further exacerbated by the loss of ygiB and ygiC genes expressed in the same operon as tolC and their homologues yjfM and yjfC located elsewhere on the chromosome. Our results show that this growth deficiency is caused by depletion of the critical metabolite NAD(+) and high NADH/NAD(+) ratios. The increased amounts of PspA and decreased rates of NADH oxidation in Delta tolC membranes indicated stress on the membrane and dissipation of a proton motive force. We conclude that inactivation of TolC triggers metabolic shutdown in E. coli cells grown in minimal glucose medium. The Delta tolC phenotype is partially rescued by YgiBC and YjfMC, which have parallel functions independent from TolC.",
"title": "Metabolic shutdown in Escherichia coli cells lacking the outer membrane channel TolC."
},
{
"docid": "24725136",
"text": "BACKGROUND The combination of ataxia and hypogonadism was first described more than a century ago, but its genetic basis has remained elusive. METHODS We performed whole-exome sequencing in a patient with ataxia and hypogonadotropic hypogonadism, followed by targeted sequencing of candidate genes in similarly affected patients. Neurologic and reproductive endocrine phenotypes were characterized in detail. The effects of sequence variants and the presence of an epistatic interaction were tested in a zebrafish model. RESULTS Digenic homozygous mutations in RNF216 and OTUD4, which encode a ubiquitin E3 ligase and a deubiquitinase, respectively, were found in three affected siblings in a consanguineous family. Additional screening identified compound heterozygous truncating mutations in RNF216 in an unrelated patient and single heterozygous deleterious mutations in four other patients. Knockdown of rnf216 or otud4 in zebrafish embryos induced defects in the eye, optic tectum, and cerebellum; combinatorial suppression of both genes exacerbated these phenotypes, which were rescued by nonmutant, but not mutant, human RNF216 or OTUD4 messenger RNA. All patients had progressive ataxia and dementia. Neuronal loss was observed in cerebellar pathways and the hippocampus; surviving hippocampal neurons contained ubiquitin-immunoreactive intranuclear inclusions. Defects were detected at the hypothalamic and pituitary levels of the reproductive endocrine axis. CONCLUSIONS The syndrome of hypogonadotropic hypogonadism, ataxia, and dementia can be caused by inactivating mutations in RNF216 or by the combination of mutations in RNF216 and OTUD4. These findings link disordered ubiquitination to neurodegeneration and reproductive dysfunction and highlight the power of whole-exome sequencing in combination with functional studies to unveil genetic interactions that cause disease. (Funded by the National Institutes of Health and others.).",
"title": "Ataxia, dementia, and hypogonadotropism caused by disordered ubiquitination."
},
{
"docid": "7717468",
"text": "Microbial survival in a host is usually dependent on the ability of a pathogen to undergo changes that promote escape from host defense mechanisms. The human-pathogenic fungus Cryptococcus neoformans undergoes phenotypic switching in vivo that promotes persistence in tissue. By microarray and real-time PCR analyses, the allergen 1 gene (ALL1) was found to be downregulated in the hypervirulent mucoid switch variant, both during logarithmic growth and during intracellular growth in macrophages. The ALL1 gene encodes a small cytoplasmic protein that is involved in capsule formation. Growth of an all1Delta gene deletion mutant was normal. Similar to cells of the mucoid switch variant, all1Delta cells produced a larger polysaccharide capsule than cells of the smooth parent and the complemented strain produced, and the enlarged capsule inhibited macrophage phagocytosis. The mutant exhibited a modest defect in capsule induction compared to all of the other variants. In animal models the phenotype of the all1Delta mutant mimicked the hypervirulent phenotype of the mucoid switch variant, which is characterized by decreased host survival and elevated intracranial pressure. Decreased survival is likely the result of both an ineffective cell-mediated immune response and impaired phagocytosis by macrophages. Consequently, we concluded that, unlike loss of most virulence-associated genes, where loss of gene function results in attenuated virulence, loss of the ALL1 gene enhances virulence by altering the host-pathogen interaction and thereby impairing clearance. Our data identified the first cryptococcal gene associated with elevated intracranial pressure and support the hypothesis that an environmental opportunistic pathogen has modified its virulence in vivo by epigenetic downregulation of gene function.",
"title": "Loss of allergen 1 confers a hypervirulent phenotype that resembles mucoid switch variants of Cryptococcus neoformans."
},
{
"docid": "14471161",
"text": "Circadian disruption accelerates cancer progression, whereas circadian reinforcement could halt it. Mice with P03 pancreatic adenocarcinoma (n = 77) were synchronized and fed ad libitum (AL) or with meal timing (MT) from Zeitgeber time (ZT) 2 to ZT6 with normal or fat diet. Tumor gene expression profiling was determined with DNA microarrays at endogenous circadian time (CT) 4 and CT16. Circadian mRNA expression patterns were determined for clock genes Rev-erbalpha, Per2, and Bmal1, cellular stress genes Hspa8 and Cirbp, and cyclin A2 gene Ccna2 in liver and tumor. The 24-hour patterns in telemetered rest-activity and body temperature and plasma corticosterone and insulin-like growth factor-I (IGF-I) were assessed. We showed that MT inhibited cancer growth by approximately 40% as compared with AL (P = 0.011) irrespective of calorie intake. Clock gene transcription remained arrhythmic in tumors irrespective of feeding schedule or diet. Yet, MT upregulated or downregulated the expression of 423 tumor genes, according to CT. Moreover, 36 genes involved in cellular stress, cell cycle, and metabolism were upregulated at one CT and downregulated 12 h apart. MT induced >10-fold circadian expression of Hspa8, Cirbp, and Ccna2 in tumors. Corticosterone or IGF-I patterns played no role in tumor growth inhibition. In contrast, MT consistently doubled the circadian amplitude of body temperature. Peak and trough respectively corresponded to peak expressions of Hspa8 and Cirbp in tumors. The reinforcement of the host circadian timing system with MT induced 24-hour rhythmic expression of critical genes in clock-deficient tumors, which translated into cancer growth inhibition. Targeting circadian clocks represents a novel potential challenge for cancer therapeutics.",
"title": "Cancer inhibition through circadian reprogramming of tumor transcriptome with meal timing."
},
{
"docid": "29564505",
"text": "IMPORTANCE Exacerbations of respiratory symptoms in chronic obstructive pulmonary disease (COPD) have profound and long-lasting adverse effects on patients. OBJECTIVE To test the hypothesis that elevated levels of inflammatory biomarkers in individuals with stable COPD are associated with an increased risk of having exacerbations. DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study examining 61,650 participants with spirometry measurements from the Copenhagen City Heart Study (2001-2003) and the Copenhagen General Population Study (2003-2008). Of these, 6574 had COPD, defined as a ratio between forced expiratory volume in 1 second (FEV1) and forced vital capacity below 0.7. MAIN OUTCOMES AND MEASURES Baseline levels of C-reactive protein (CRP) and fibrinogen and leukocyte count were measured in participants at a time when they were not experiencing symptoms of exacerbations. Exacerbations were recorded and defined as short-course treatment with oral corticosteroids alone or in combination with an antibiotic or as a hospital admission due to COPD. Levels of CRP and fibrinogen and leukocyte count were defined as high or low according to cut points of 3 mg/L, 14 μmol/L, and 9 ×10(9)/L, respectively. RESULTS During follow-up, 3083 exacerbations were recorded (mean, 0.5/participant). In the first year of follow-up, multivariable-adjusted odds ratios for having frequent exacerbations were 1.2 (95% CI, 0.7-2.2; 17 events/1000 person-years) for individuals with 1 high biomarker, 1.7 (95% CI, 0.9-3.2; 32 events/1000 person-years) for individuals with 2 high biomarkers, and 3.7 (95% CI, 1.9-7.4; 81 events/1000 person-years) for individuals with 3 high biomarkers compared with individuals who had no elevated biomarkers (9 events/1000 person-years; trend: P = 2 × 10(-5)). Corresponding hazard ratios using maximum follow-up time were 1.4 (95% CI, 1.1-1.8), 1.6 (95% CI, 1.3-2.2), and 2.5 (95% CI, 1.8-3.4), respectively (trend: P = 1 × 10(-8)). The addition of inflammatory biomarkers to a basic model including age, sex, FEV1 percent predicted, smoking, use of any inhaled medication, body mass index, history of previous exacerbations, and time since most recent prior exacerbation improved the C statistics from 0.71 to 0.73 (comparison: P = 9 × 10(-5)). Relative risks were consistent in those with milder COPD, in those with no history of frequent exacerbations, and in the 2 studies separately. The highest 5-year absolute risks of having frequent exacerbations in those with 3 high biomarkers (vs no high biomarkers) were 62% (vs 24%) for those with Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades C-D (n = 558), 98% (vs 64%) in those with a history of frequent exacerbations (n = 127), and 52% (vs 15%) for those with GOLD grades 3-4 (n = 465). CONCLUSIONS AND RELEVANCE Simultaneously elevated levels of CRP and fibrinogen and leukocyte count in individuals with COPD were associated with increased risk of having exacerbations, even in those with milder COPD and in those without previous exacerbations. Further investigation is needed to determine the clinical value of these biomarkers for risk stratification.",
"title": "Inflammatory biomarkers and exacerbations in chronic obstructive pulmonary disease."
},
{
"docid": "23117928",
"text": "Infection of Sulfolobus islandicus REY15A with mixtures of different Sulfolobus viruses, including STSV2, did not induce spacer acquisition by the host CRISPR immune system. However, coinfection with the tailed fusiform viruses SMV1 and STSV2 generated hyperactive spacer acquisition in both CRISPR loci, exclusively from STSV2, with the resultant loss of STSV2 but not SMV1. SMV1 was shown to activate adaptation while itself being resistant to CRISPR-mediated adaptation and DNA interference. Exceptionally, a single clone S-1 isolated from an SMV1 + STSV2-infected culture, that carried STSV2-specific spacers and had lost STSV2 but not SMV1, acquired spacers from SMV1. This effect was also reproducible on reinfecting wild-type host cells with a variant SMV1 isolated from the S-1 culture. The SMV1 variant lacked a virion protein ORF114 that was shown to bind DNA. This study also provided evidence for: (i) limits on the maximum sizes of CRISPR loci; (ii) spacer uptake strongly retarding growth of infected cultures; (iii) protospacer selection being essentially random and non-directional, and (iv) the reversible uptake of spacers from STSV2 and SMV1. A hypothesis is presented to explain the interactive conflicts between SMV1 and the host CRISPR immune system.",
"title": "Inter-viral conflicts that exploit host CRISPR immune systems of Sulfolobus."
},
{
"docid": "6766459",
"text": "Fever is commonly used to diagnose disease and is consistently associated with increased mortality in critically ill patients. However, the molecular controls of elevated body temperature are poorly understood. We discovered that the expression of RNA-binding motif protein 3 (RBM3), known to respond to cold stress and to modulate microRNA (miRNA) expression, was reduced in 30 patients with fever, and in THP-1-derived macrophages maintained at a fever-like temperature (40 °C). Notably, RBM3 expression is reduced during fever whether or not infection is demonstrable. Reduced RBM3 expression resulted in increased expression of RBM3-targeted temperature-sensitive miRNAs, we termed thermomiRs. ThermomiRs such as miR-142-5p and miR-143 in turn target endogenous pyrogens including IL-6, IL6ST, TLR2, PGE2 and TNF to complete a negative feedback mechanism, which may be crucial to prevent pathological hyperthermia. Using normal PBMCs that were exogenously exposed to fever-like temperature (40 °C), we further demonstrate the trend by which decreased levels of RBM3 were associated with increased levels of miR-142-5p and miR-143 and vice versa over a 24 h time course. Collectively, our results indicate the existence of a negative feedback loop that regulates fever via reduced RBM3 levels and increased expression of miR-142-5p and miR-143.",
"title": "RBM3 regulates temperature sensitive miR-142–5p and miR-143 (thermomiRs), which target immune genes and control fever"
},
{
"docid": "26596106",
"text": "In the yeast S. cerevisiae, ribosome assembly is linked to environmental conditions by the coordinate transcriptional regulation of genes required for ribosome biogenesis. In this study we show that two nonessential stress-responsive genes, YAR1 and LTV1, function in 40S subunit production. We provide genetic and biochemical evidence that Yar1, a small ankyrin-repeat protein, physically interacts with RpS3, a component of the 40S subunit, and with Ltv1, a protein recently identified as a substoichiometric component of a 43S preribosomal particle. We demonstrate that cells lacking YAR1 or LTV1 are hypersensitive to particular protein synthesis inhibitors and exhibit aberrant polysome profiles, with a reduced absolute number of 40S subunits and an excess of free 60S subunits. Surprisingly, both mutants are also hypersensitive to a variety of environmental stress conditions. Overexpression of RPS3 suppresses both the stress sensitivity and the ribosome biogenesis defect of Deltayar1 mutants, but does not suppress either defect in Deltaltv1 mutants. We propose that YAR1 and LTV1 play distinct, nonessential roles in 40S subunit production. The stress-sensitive phenotypes of strains lacking these genes reveal a hitherto unknown link between ribosome biogenesis factors and environmental stress sensitivity.",
"title": "Genetic and biochemical interactions among Yar1, Ltv1 and Rps3 define novel links between environmental stress and ribosome biogenesis in Saccharomyces cerevisiae."
},
{
"docid": "34016944",
"text": "PURPOSE Tyrosine kinase (TK) inhibitors are emerging as a promising new approach to the treatment of HER overexpressing tumors, however optimal use of these agents awaits further definition of the downstream signaling pathways that mediate their effects. We reported previously that both EGFR- and Her2-overexpressing tumors are sensitive to the new EGFR-selective TK inhibitor gefitinib (ZD1839, \"Iressa\"), and sensitivity to this agent correlated with its ability to down-regulate Akt. However, EGFR-overexpressing MDA-468 cells, which lack PTEN function, are resistant to ZD1839, and ZD1839 is unable to down-regulate Akt activity in these cells. EXPERIMENTAL DESIGN To study the role of PTEN function, we generated MDA468 cells with tet-inducible PTEN expression. RESULTS We show here that the resistance of MDA-468 cells to ZD1839 is attributable to EGFR-independent constitutive Akt activation caused by loss of PTEN function in these cells. Reconstitution of PTEN function through tet-inducible expression restores ZD1839 sensitivity to these cells and reestablishes EGFR-stimulated Akt signaling. Although restoration of PTEN function to tumors is difficult to implement clinically, much of the effects of PTEN loss are attributable to overactive PI3K/Akt pathway signaling, and this overactivity can be modulated by pharmacologic approaches. We show here that pharmacologic down-regulation of constitutive PI3K/Akt pathway signaling using the PI3K inhibitor LY294002 similarly restores EGFR-stimulated Akt signaling and sensitizes MDA-468 cells to ZD1839. CONCLUSIONS Sensitivity to ZD1839 requires intact growth factor receptor-stimulated Akt signaling activity. PTEN loss leads to uncoupling of this signaling pathway and results in ZD1839 resistance, which can be reversed with reintroduction of PTEN or pharmacologic down-regulation of constitutive PI3K/Akt pathway activity. These data have important predictive and therapeutic clinical implications.",
"title": "Resistance to gefitinib in PTEN-null HER-overexpressing tumor cells can be overcome through restoration of PTEN function or pharmacologic modulation of constitutive phosphatidylinositol 3'-kinase/Akt pathway signaling."
},
{
"docid": "22362025",
"text": "Small regulatory RNAs are key regulators of gene expression. One class of small regulatory RNAs, termed the endogenous small interfering RNAs (endo siRNAs), is thought to negatively regulate cellular transcripts via an RNA interference (RNAi)-like mechanism termed endogenous RNAi (endo RNAi). A complex of proteins composed of ERI-1/3/5, RRF-3, and DICER (the ERI/DICER complex) mediates endo RNAi processes in Caenorhabditis elegans. We conducted a genetic screen to identify additional components of the endo RNAi machinery. Our screen recovered alleles of eri-9, which encodes a novel DICER-interacting protein, and a missense mutation within the helicase domain of DICER [DCR-1(G492R)]. ERI-9(-) and DCR-1(G492) animals exhibit defects in endo siRNA expression and a concomitant failure to regulate mRNAs that exhibit sequence homology to these endo siRNAs, indicating that ERI-9 and the DCR-1 helicase domain function in the C. elegans endo RNAi pathway. We define a subset of Eri mutant animals (including eri-1, rrf-3, eri-3, and dcr-1, but not eri-9 or ergo-1) that exhibit temperature-sensitive, sperm-specific sterility and defects in X chromosome segregation. Among these mutants we find multiple aberrations in sperm development beginning with cytokinesis and extending through terminal differentiation. These results identify novel components of the endo RNAi machinery, demonstrate differential requirements for the Eri factors in the sperm-producing germline, and begin to delineate the functional requirement for the ERI/DICER complex in sperm development.",
"title": "Requirement for the ERI/DICER complex in endogenous RNA interference and sperm development in Caenorhabditis elegans."
},
{
"docid": "9315213",
"text": "BACKGROUND Fibroblast growth factor 21 (FGF21) is a metabolic hormone with pleiotropic effects on glucose and lipid metabolism and insulin sensitivity. It acts as a key downstream target of both peroxisome proliferator-activated receptor α and γ, the agonists of which have been used for lipid lowering and insulin sensitization, respectively. However, the role of FGF21 in the cardiovascular system remains elusive. METHODS AND RESULTS The roles of FGF21 in atherosclerosis were investigated by evaluating the impact of FGF21 deficiency and replenishment with recombinant FGF21 in apolipoprotein E(-/-) mice. FGF21 deficiency causes a marked exacerbation of atherosclerotic plaque formation and premature death in apolipoprotein E(-/-) mice, which is accompanied by hypoadiponectinemia and severe hypercholesterolemia. Replenishment of FGF21 protects against atherosclerosis in apolipoprotein E(-/-)mice via 2 independent mechanisms, inducing the adipocyte production of adiponectin, which in turn acts on the blood vessels to inhibit neointima formation and macrophage inflammation, and suppressing the hepatic expression of the transcription factor sterol regulatory element-binding protein-2, thereby leading to reduced cholesterol synthesis and attenuation of hypercholesterolemia. Chronic treatment with adiponectin partially reverses atherosclerosis without obvious effects on hypercholesterolemia in FGF21-deficient apolipoprotein E(-/-) mice. By contrast, the cholesterol-lowering effects of FGF21 are abrogated by hepatic expression of sterol regulatory element-binding protein-2. CONCLUSIONS FGF21 protects against atherosclerosis via fine tuning the multiorgan crosstalk among liver, adipose tissue, and blood vessels.",
"title": "Fibroblast Growth Factor 21 Prevents Atherosclerosis by Suppression of Hepatic Sterol Regulatory Element-Binding Protein-2 and Induction of Adiponectin in Mice"
},
{
"docid": "10169908",
"text": "PURPOSE We have previously identified solute-linked carrier family A1 member 5 (SLC1A5) as an overexpressed protein in a shotgun proteomic analysis of stage I non-small cell lung cancer (NSCLC) when compared with matched controls. We hypothesized that overexpression of SLC1A5 occurs to meet the metabolic demand for lung cancer cell growth and survival. EXPERIMENTAL DESIGN To test our hypothesis, we first analyzed the protein expression of SLC1A5 in archival lung cancer tissues by immunohistochemistry and immunoblotting (N = 98) and in cell lines (N = 36). To examine SLC1A5 involvement in amino acid transportation, we conducted kinetic analysis of l-glutamine (Gln) uptake in lung cancer cell lines in the presence and absence of a pharmacologic inhibitor of SLC1A5, gamma-l-Glutamyl-p-Nitroanilide (GPNA). Finally, we examined the effect of Gln deprivation and uptake inhibition on cell growth, cell-cycle progression, and growth signaling pathways of five lung cancer cell lines. RESULTS Our results show that (i) SLC1A5 protein is expressed in 95% of squamous cell carcinomas (SCC), 74% of adenocarcinomas (ADC), and 50% of neuroendocrine tumors; (ii) SLC1A5 is located at the cytoplasmic membrane and is significantly associated with SCC histology and male gender; (iii) 68% of Gln is transported in a Na(+)-dependent manner, 50% of which is attributed to SLC1A5 activity; and (iv) pharmacologic and genetic targeting of SLC1A5 decreased cell growth and viability in lung cancer cells, an effect mediated in part by mTOR signaling. CONCLUSIONS These results suggest that SLC1A5 plays a key role in Gln transport controlling lung cancer cells' metabolism, growth, and survival.",
"title": "SLC1A5 mediates glutamine transport required for lung cancer cell growth and survival."
},
{
"docid": "22522432",
"text": "The stable contact of ISW2 with nucleosomal DNA approximately 20 bp from the dyad was shown by DNA footprinting and photoaffinity labeling using recombinant histone octamers to require the histone H4 N-terminal tail. Efficient ISW2 remodeling also required the H4 N-terminal tail, although the lack of the H4 tail can be mostly compensated for by increasing the incubation time or concentration of ISW2. Similarly, the length of extranucleosomal DNA affected the stable contact of ISW2 with this same internal nucleosomal site, with the optimal length being 70 to 85 bp. These data indicate the histone H4 tail, in concert with a favorable length of extranucleosomal DNA, recruits and properly orients ISW2 onto the nucleosome for efficient nucleosome remodeling. One consequence of this property of ISW2 is likely its previously observed nucleosome spacing activity.",
"title": "Regulation of ISW2 by concerted action of histone H4 tail and extranucleosomal DNA."
},
{
"docid": "12225214",
"text": "Ubiquitination controls a broad range of cellular functions. The last step of the ubiquitination pathway is regulated by enzyme type 3 (E3) ubiquitin ligases. E3 enzymes are responsible for substrate specificity and catalyze the formation of an isopeptide bond between a lysine residue of the substrate (or the N terminus of the substrate) and ubiquitin. MIR1 and MIR2 are two E3 ubiquitin ligases encoded by Kaposi's sarcoma-associated herpesvirus that mediate the ubiquitination of major histocompatibility complex class I (MHC I) molecules and subsequent internalization. Here, we found that MIR1, but not MIR2, promoted down-regulation of MHC I molecules lacking lysine residues in their intracytoplasmic domain. In the presence of MIR1, these MHC I molecules were ubiquitinated, and their association with ubiquitin was sensitive to beta2-mercaptoethanol, unlike lysine-ubiquitin bonds. This form of ubiquitination required a cysteine residue in the intracytoplasmic tail of MHC I molecules. An MHC I molecule containing a single cysteine residue in an artificial glycine and alanine intracytoplasmic domain was endocytosed and degraded in the presence of MIR1. Thus, ubiquitination can occur on proteins lacking accessible lysines or an accessible N terminus.",
"title": "Ubiquitination on nonlysine residues by a viral E3 ubiquitin ligase."
},
{
"docid": "435529",
"text": "HEN1-mediated 2'-O-methylation has been shown to be a key mechanism to protect plant microRNAs (miRNAs) and small interfering RNAs (siRNAs) as well as animal piwi-interacting RNAs (piRNAs) from degradation and 3' terminal uridylation [1-8]. However, enzymes uridylating unmethylated miRNAs, siRNAs, or piRNAs in hen1 are unknown. In this study, a genetic screen identified a second-site mutation hen1 suppressor1-2 (heso1-2) that partially suppresses the morphological phenotypes of the hypomorphic hen1-2 allele and the null hen1-1 allele in Arabidopsis. HESO1 encodes a terminal nucleotidyl transferase that prefers to add untemplated uridine to the 3' end of RNA, which is completely abolished by 2'-O-methylation. heso1-2 affects the profile of u-tailed miRNAs and siRNAs and increases the abundance of truncated and/or normal sized ones in hen1, which often results in increased total amount of miRNAs and siRNAs in hen1. In contrast, overexpressing HESO1 in hen1-2 causes more severe morphological defects and less accumulation of miRNAs. These results demonstrate that HESO1 is an enzyme uridylating unmethylated miRNAs and siRNAs in hen1. These observations also suggest that uridylation may destabilize unmethylated miRNAs through an unknown mechanism and compete with 3'-to-5' exoribonuclease activities in hen1. This study shall have implications on piRNA uridylation in hen1 in animals.",
"title": "Uridylation of miRNAs by HEN1 SUPPRESSOR1 in Arabidopsis"
},
{
"docid": "4455466",
"text": "Recognition of modified histones by ‘reader’ proteins plays a critical role in the regulation of chromatin. H3K36 trimethylation (H3K36me3) is deposited onto the nucleosomes in the transcribed regions after RNA polymerase II elongation. In yeast, this mark in turn recruits epigenetic regulators to reset the chromatin to a relatively repressive state, thus suppressing cryptic transcription. However, much less is known about the role of H3K36me3 in transcription regulation in mammals. This is further complicated by the transcription-coupled incorporation of the histone variant H3.3 in gene bodies. Here we show that the candidate tumour suppressor ZMYND11 specifically recognizes H3K36me3 on H3.3 (H3.3K36me3) and regulates RNA polymerase II elongation. Structural studies show that in addition to the trimethyl-lysine binding by an aromatic cage within the PWWP domain, the H3.3-dependent recognition is mediated by the encapsulation of the H3.3-specific ‘Ser 31’ residue in a composite pocket formed by the tandem bromo–PWWP domains of ZMYND11. Chromatin immunoprecipitation followed by sequencing shows a genome-wide co-localization of ZMYND11 with H3K36me3 and H3.3 in gene bodies, and its occupancy requires the pre-deposition of H3.3K36me3. Although ZMYND11 is associated with highly expressed genes, it functions as an unconventional transcription co-repressor by modulating RNA polymerase II at the elongation stage. ZMYND11 is critical for the repression of a transcriptional program that is essential for tumour cell growth; low expression levels of ZMYND11 in breast cancer patients correlate with worse prognosis. Consistently, overexpression of ZMYND11 suppresses cancer cell growth in vitro and tumour formation in mice. Together, this study identifies ZMYND11 as an H3.3-specific reader of H3K36me3 that links the histone-variant-mediated transcription elongation control to tumour suppression.",
"title": "ZMYND11 links histone H3.3K36me3 to transcription elongation and tumour suppression"
},
{
"docid": "18676539",
"text": "FANCM is a component of the Fanconi anemia (FA) core complex and one FA patient (EUFA867) with biallelic mutations in FANCM has been described. Strikingly, we found that EUFA867 also carries biallelic mutations in FANCA. After correcting the FANCA defect in EUFA867 lymphoblasts, a \"clean\" FA-M cell line was generated. These cells were hypersensitive to mitomycin C, but unlike cells defective in other core complex members, FANCM(-/-) cells were proficient in monoubiquitinating FANCD2 and were sensitive to the topoisomerase inhibitor camptothecin, a feature shared only with the FA subtype D1 and N. In addition, FANCM(-/-) cells were sensitive to UV light. FANCM and a C-terminal deletion mutant rescued the cross-linker sensitivity of FANCM(-/-) cells, whereas a FANCM ATPase mutant did not. Because both mutants restored the formation of FANCD2 foci, we conclude that FANCM functions in an FA core complex-dependent and -independent manner.",
"title": "Impaired FANCD2 monoubiquitination and hypersensitivity to camptothecin uniquely characterize Fanconi anemia complementation group M."
},
{
"docid": "519974",
"text": "Mammals detect temperature with specialized neurons in the peripheral nervous system. Four TRPV-class channels have been implicated in sensing heat, and one TRPM-class channel in sensing cold. The combined range of temperatures that activate these channels covers a majority of the relevant physiological spectrum sensed by most mammals, with a significant gap in the noxious cold range. Here, we describe the characterization of ANKTM1, a cold-activated channel with a lower activation temperature compared to the cold and menthol receptor, TRPM8. ANKTM1 is a distant family member of TRP channels with very little amino acid similarity to TRPM8. It is found in a subset of nociceptive sensory neurons where it is coexpressed with TRPV1/VR1 (the capsaicin/heat receptor) but not TRPM8. Consistent with the expression of ANKTM1, we identify noxious cold-sensitive sensory neurons that also respond to capsaicin but not to menthol.",
"title": "ANKTM1, a TRP-like Channel Expressed in Nociceptive Neurons, Is Activated by Cold Temperatures"
},
{
"docid": "2820454",
"text": "BACKGROUND Pulmonary hypertension (PH) is associated with restricted physical capacity, limited quality of life, and a poor prognosis because of right heart failure. The present study is the first prospective randomized study to evaluate the effects of exercise and respiratory training in patients with severe symptomatic PH. METHODS AND RESULTS Thirty patients with PH (21 women; mean age, 50+/-13 years; mean pulmonary artery pressure, 50+/-15 mm Hg; mean World Health Organization [WHO] class, 2.9+/-0.5; pulmonary arterial hypertension, n=23; chronic thromboembolic PH, n=7) on stable disease-targeted medication were randomly assigned to a control (n=15) and a primary training (n=15) group. Medication remained unchanged during the study period. Primary end points were the changes from baseline to week 15 in the distance walked in 6 minutes and in scores of the Short Form Health Survey quality-of-life questionnaire. Changes in WHO functional class, Borg scale, and parameters of echocardiography and gas exchange also were assessed. At week 15, patients in the primary and secondary training groups had an improved 6-minute walking distance; the mean difference between the control and the primary training group was 111 m (95% confidence interval, 65 to 139 m; P<0.001). Exercise training was well tolerated and improved scores of quality of life, WHO functional class, peak oxygen consumption, oxygen consumption at the anaerobic threshold, and achieved workload. Systolic pulmonary artery pressure values at rest did not change significantly after 15 weeks of exercise and respiratory training (from 61+/-18 to 54+/-18 mm Hg) within the training group. CONCLUSIONS This study indicates that respiratory and physical training could be a promising adjunct to medical treatment in severe PH. The effects add to the beneficial results of modern medical treatment.",
"title": "Exercise and respiratory training improve exercise capacity and quality of life in patients with severe chronic pulmonary hypertension."
},
{
"docid": "5760247",
"text": "Chromosome segregation during mitosis requires assembly of the kinetochore complex at the centromere. Kinetochore assembly depends on specific recognition of the histone variant CENP-A in the centromeric nucleosome by centromere protein C (CENP-C). We have defined the determinants of this recognition mechanism and discovered that CENP-C binds a hydrophobic region in the CENP-A tail and docks onto the acidic patch of histone H2A and H2B. We further found that the more broadly conserved CENP-C motif uses the same mechanism for CENP-A nucleosome recognition. Our findings reveal a conserved mechanism for protein recruitment to centromeres and a histone recognition mode whereby a disordered peptide binds the histone tail through hydrophobic interactions facilitated by nucleosome docking.",
"title": "A conserved mechanism for centromeric nucleosome recognition by centromere protein CENP-C."
},
{
"docid": "121581019",
"text": "High-quality indium–tin–oxide (ITO) thin films (200–850 nm) have been grown by pulsed laser deposition (PLD) on glass substrates without a postdeposition annealing treatment. The structural, electrical, and optical properties of these films have been investigated as a function of target composition, substrate deposition temperature, background gas pressure, and film thickness. Films were deposited from various target compositions ranging from 0 to 15 wt % of SnO2 content. The optimum target composition for high conductivity was 5 wt % SnO2+95 wt % In2O3. Films were deposited at substrate temperatures ranging from room temperature to 300 °C in O2 partial pressures ranging from 1 to 100 mTorr. Films were deposited using a KrF excimer laser (248 nm, 30 ns full width at half maximum) at a fluence of 2 J/cm2. For a 150-nm-thick ITO film grown at room temperature in an oxygen pressure of 10 mTorr, the resistivity was 4×10−4 Ω cm and the average transmission in the visible range (400–700 nm) was 85%. For a 170-n...",
"title": "Electrical, optical, and structural properties of indium-tin-oxide thin films for organic light-emitting devices"
},
{
"docid": "1970884",
"text": "Viruses that replicate in the cytoplasm cannot access the host nuclear capping machinery. These viruses have evolved viral methyltransferase(s) to methylate N-7 and 2'-O cap of their RNA; alternatively, they \"snatch\" host mRNA cap to form the 5' end of viral RNA. The function of 2'-O methylation of viral RNA cap is to mimic cellular mRNA and to evade host innate immune restriction. A cytoplasmic virus defective in 2'-O methylation is replicative, but its viral RNA lacks 2'-O methylation and is recognized and eliminated by the host immune response. Such a mutant virus could be rationally designed as a live attenuated vaccine. Here, we use Japanese encephalitis virus (JEV), an important mosquito-borne flavivirus, to prove this novel vaccine concept. We show that JEV methyltransferase is responsible for both N-7 and 2'-O cap methylations as well as evasion of host innate immune response. Recombinant virus completely defective in 2'-O methylation was stable in cell culture after being passaged for >30 days. The mutant virus was attenuated in mice, elicited robust humoral and cellular immune responses, and retained the engineered mutation in vivo. A single dose of immunization induced full protection against lethal challenge with JEV strains in mice. Mechanistically, the attenuation phenotype was attributed to the enhanced sensitivity of the mutant virus to the antiviral effects of interferon and IFIT proteins. Collectively, the results demonstrate the feasibility of using 2'-O methylation-defective virus as a vaccine approach; this vaccine approach should be applicable to other flaviviruses and nonflaviviruses that encode their own viral 2'-O methyltransferases.",
"title": "Rational design of a flavivirus vaccine by abolishing viral RNA 2'-O methylation."
},
{
"docid": "43014661",
"text": "Xeroderma pigmentosum variant (XPV) patients with mutations in the DNA polymerase eta (pol eta) gene are hypersensitive to sunlight and have greatly increased susceptibility to sunlight-induced skin cancer. Consistent with the ability of Pol eta to efficiently bypass UV light-induced cyclobutane pyrimidine dimers, XPV cells lacking Pol eta have diminished capacity to replicate UV-damaged DNA and are sensitive to UV light-induced killing and mutagenesis. To better understand these and other Pol eta functions, we generated Pol eta-deficient mice. Mice homozygous for a null mutation in pol eta are viable, fertile, and do not show any obvious spontaneous defects during the first year of life. However, fibroblasts derived from these mutant mice are sensitive to killing by exposure to UV light, and all Pol eta-deficient mice develop skin tumors after UV irradiation, in contrast to the wild-type littermate controls that did not develop such tumors. These results and biochemical studies of translesion synthesis by mouse Pol eta indicate that Pol eta-dependent bypass of cyclobutane pyrimidine dimers suppresses UV light-induced skin cancer in mice. Moreover, 37.5% of pol eta heterozygous mice also developed skin cancer during 5 months after a 5-month exposure to UV light, suggesting that humans who are heterozygous for mutations in pol eta may also have an increased risk of skin cancer.",
"title": "Increased susceptibility to UV-induced skin carcinogenesis in polymerase eta-deficient mice."
}
] |
5abf7dd75542994516f454b4
|
What continent is the home of both Alternanthera and Platycodon species?
|
[
{
"docid": "937482",
"text": "Alternanthera is a genus of flowering plants in the amaranth family, Amaranthaceae. It is a widespread genus with most species occurring in the tropical Americas, and others in Asia, Africa, and Australia. Plants of the genus may be known generally as joyweeds, or Joseph's coat. Several species are notorious noxious weeds.",
"title": ""
},
{
"docid": "2180238",
"text": "Platycodon grandiflorus (from Ancient Greek πλατύς \"wide\" and κώδων \"bell\") is a species of herbaceous flowering perennial plant of the family Campanulaceae, and the only member of the genus Platycodon. It is native to East Asia (China, Korea, Japan, and the Russian Far East). It is commonly known as balloon flower (referring to the balloon-shaped flower buds), Chinese bellflower, or platycodon.",
"title": ""
}
] |
[
{
"docid": "12854725",
"text": "Alternanthera flavicoma is a species of plant in the Amaranthaceae family. It is endemic to Ecuador.",
"title": ""
},
{
"docid": "12854732",
"text": "Alternanthera galapagensis is a species of plant in the Amaranthaceae family. It is endemic to Ecuador.",
"title": ""
},
{
"docid": "12854755",
"text": "Alternanthera snodgrassii is a species of plant in the Amaranthaceae family. It is endemic to Ecuador.",
"title": ""
},
{
"docid": "47045917",
"text": "Alternanthera echinocephala, known as spiny-headed chaff flower, is a shrubby plant in the amaranth family (Amaranthaceae) native to the Galápagos Islands, mainland Ecuador, and Peru. Its relatively large spiny \"heads\" of flowers distinguish it from other species of \"Alternanthera\" found in the Galápagos.",
"title": ""
},
{
"docid": "11540265",
"text": "Alternanthera littoralis is an African species in the botanical family Amaranthaceae. The leaves are eaten as a vegetable.",
"title": ""
},
{
"docid": "12854721",
"text": "Alternanthera filifolia is a species of flowering plant in the amaranth family, Amaranthaceae. It is native to the Galápagos Islands.",
"title": ""
},
{
"docid": "12854746",
"text": "Alternanthera nesiotes is a species of flowering plant in the family Amaranthaceae. It is endemic to the Galápagos Islands, where it is limited to Floreana Island. There are five subpopulations which are susceptible to habitat degradation due to invasive species of plants and animals.",
"title": ""
},
{
"docid": "7064435",
"text": "Alternanthera reineckii is a species of aquatic plant in the amaranth family, Amaranthaceae. Several cultivars are used as ornamental plants in aquaria.",
"title": ""
},
{
"docid": "12854709",
"text": "Alternanthera areschougii is a species of plant in the Amaranthaceae family. It is endemic to Ecuador. Its natural habitats are subtropical or tropical dry forests and subtropical or tropical dry shrubland. It is threatened by habitat loss.",
"title": ""
},
{
"docid": "1118925",
"text": "Alternanthera philoxeroides, commonly referred to as alligator weed, is a native species to the temperate regions of South America, which includes Argentina, Brazil, Paraguay and Uruguay. Argentina alone, hosts around 27 species that fall within the range of the genus Alternanthera. Its geographic range once used to cover only the Parana River region of South America, but it has since expanded to cover over 30 countries, such as the United States, New Zealand, China and many more. This invasive species is believed to have been accidentally introduced to these non-native regions through sediments trapped/attached to tanks and cargo of ships travelling from South America to these various areas.",
"title": ""
},
{
"docid": "12854716",
"text": "Alternanthera corymbiformis is a species of plant in the Amaranthaceae family. It is endemic to Ecuador. Its natural habitats are subtropical or tropical moist montane forests and subtropical or tropical dry shrubland. It is threatened by habitat loss.",
"title": ""
},
{
"docid": "12854738",
"text": "Alternanthera grandis is a species of plant in the Amaranthaceae family. It is endemic to Ecuador. Its natural habitats are subtropical or tropical dry forests, subtropical or tropical dry shrubland, and subtropical or tropical high-altitude grassland. It is threatened by habitat loss. This plant is known for its connection to the Memphis Grizzlies. The players on this team all have an insignia of Alternanthera grandis on their shorts during every away game. The species name, Grandis, refers to the Spanish word for large. This plant can be found throughout northern Ecuador and, most notably, in the Basilica of Nuestra Señora de la Merced. The plant is found near the Ark of the Holy Emblem.",
"title": ""
},
{
"docid": "12854743",
"text": "Alternanthera helleri is a species of plant in the Amaranthaceae family. It is endemic to Ecuador. It is believed to be green in color anywhere from 90 to 100% of the year depending on altitude. The leaves are considered to be highly toxic to humans and should not be consumed under any circumstances.",
"title": ""
},
{
"docid": "14611595",
"text": "Alternanthera pungens Kunth is a creeping, prostrate perennial pioneer plant of the Amaranthaceae family, spreading by seed and vegetatively, with roots often developing at the nodes of spreading stems. A plant of roadsides, path verges and waste places (ruderal), it is thought to have come from Central and South America, and to have become widely established in Australia and Southern Africa. Other species of this genus, e.g. \"Alternanthera sessilis\" (L.) R.Br. ex DC., have long been recorded from Tropical Africa, and would be difficult to prove as invaders.",
"title": ""
},
{
"docid": "25671333",
"text": "Alternanthera bettzickiana (syn. \"A. amoena\") is a species of flowering plant in the amaranth family, Amaranthaceae. It is commonly used as an ornamental edging plant. It is particularly popular in China, where it is \"cultivated in nearly all the large cities\". It is native to South America. Its common names include calico-plant.",
"title": ""
},
{
"docid": "48166751",
"text": "The North American Continent is home to a wide variety of carnivorous plant species. Species from seven genera are native to the continent, and three of these genera are found nowhere else on the planet.",
"title": ""
},
{
"docid": "48886105",
"text": "Alternanthera ficoidea is a type of herb belonging to the Amarathaceae family. It is also known as \"Alternanthera tenella,\" and is common and widespread throughout the tropics. It is in fact an endemic herb in the Western Ghats of India. However it is invasive to the island of Palau, and Philippines. The herb has been introduced to Japan, and many other Pacific islands, where they are not invasive. Propagation occurs via seeds.",
"title": ""
},
{
"docid": "9649914",
"text": "Alternanthera sessilis is an aquatic plant known by several common names, including ponnanganni (in Tamil), ponnaganti aaku (in Telugu),",
"title": ""
},
{
"docid": "21006160",
"text": "Alternanthera mosaic virus (AltMV) is a plant pathogenic virus. AltMV belongs to the virus genus \"Potexvirus\" and the virus family \"Alphaflexiviridae\".",
"title": ""
},
{
"docid": "852063",
"text": "The family Campanulaceae (also bellflower family), of the order Asterales, contains nearly 2400 species in 84 genera of herbaceous plants, shrubs, and rarely small trees, often with milky non-toxic sap. Among them are the familiar garden plants \"Campanula\" (bellflower), \"Lobelia\", and \"Platycodon\" (balloonflower).",
"title": ""
},
{
"docid": "53092133",
"text": "People who choose to run a marathon on all seven continents are generally considered to be a part of the 7 continents club. However, there is some dispute over what counts for each continent, with specific issue being taken due to races being run in \"Antarctica\" that actually take place on outlying islands of the continent and not within the continent itself.",
"title": ""
},
{
"docid": "19885253",
"text": "Sissoo spinach, also known as Brazilian spinach, Sambu or Samba lettuce, is a tropical edible groundcover of the genus \"Alternanthera\" used as a leaf vegetable. Although it is referred to scientifically as Alternanthera sissoo , there are no known scientific descriptions of its taxonomy.",
"title": ""
},
{
"docid": "689",
"text": "Asia ( ) is Earth's largest and most populous continent, located primarily in the Eastern and Northern Hemispheres. It shares the continental landmass of Eurasia with the continent of Europe and the continental landmass of Afro-Eurasia with both Europe and Africa. Asia covers an area of 44,579,000 km2 , about 30% of Earth's total land area and 8.7% of the Earth's total surface area. The continent, which has long been home to the majority of the human population, was the site of many of the first civilizations. Asia is notable for not only its overall large size and population, but also dense and large settlements as well as vast barely populated regions within the continent of /1e9 round 1 billion people, or roughly 60% of the world's population.",
"title": ""
},
{
"docid": "15478054",
"text": "Amynothrips andersoni is a species of thrips known as alligator weed thrips. It has been used as an agent of biological pest control against the noxious aquatic plant known as alligator weed (\"Alternanthera philoxeroides\").",
"title": ""
},
{
"docid": "51067860",
"text": "Gualicho (named in reference to the gualichu) is a genus of theropod dinosaur. The type species is Gualicho shinyae. \"Gualicho\" lived in what is now northern Patagonia, on what was then a South American island continent split off from the supercontinent Gondwana. The fossils were found in the Huincul Formation, dating to the late Cenomanian-early Turonian age of the upper Cretaceous Period, around 93 million years ago.",
"title": ""
},
{
"docid": "35538251",
"text": "The Biceratopsinae is an extinct subfamily of trilobites, fossil marine arthropods, with species of small to average size. Species belonging to this subfamily lived during the Toyonian stage (Upper \"Olenellus\"-zone), 516-513 million years ago, in the former continent of Laurentia, including what are today the South-Western United States and Canada.",
"title": ""
},
{
"docid": "36184564",
"text": "Biceratopsidae is an extinct family of redlichiid trilobites, with species of small to average size. Species of belonging to this family lived during the Toyonian stage (\"Olenellus\"-zone), 522–513 million years ago, in the former continent of Laurentia, including what are today the south-western United States and Canada. It contains the subfamilies Biceratopsinae and Bristoliinae.",
"title": ""
},
{
"docid": "15478247",
"text": "Arcola malloi (formerly \"Vogtia malloi\") is a species of snout moth known as the alligator weed stem borer. It is used as an agent of biological pest control against the noxious aquatic plant known as alligator weed (\"Alternanthera philoxeroides\").",
"title": ""
},
{
"docid": "1460408",
"text": "Cyperus is a large genus of about 700 species of sedges, distributed throughout all continents in both tropical and temperate regions.",
"title": ""
},
{
"docid": "1935780",
"text": "The Birmingham Zoo is a zoological park that opened in 1955 in Birmingham, Alabama (USA). The 122 acre zoo is home to almost 800 animals representing over 200 species, including many endangered species from six continents.",
"title": ""
}
] |
PLAIN-1946
|
protein
|
[
{
"docid": "MED-3302",
"text": "In November 2007 a novel neuropathy, immune-mediated polyradiculoneuropathy (IP), was identified among workers at a Minnesota swine abattoir where a unique compressed air technique was used to remove porcine brains. An epidemiologic investigation at another abattoir in Indiana that also uses this process was launched to evaluate workers self-reporting neurologic illness compatible with IP. A nested case-control study was performed to identify cases and risk factors. Six confirmed, one probable, and three possible IP cases were detected. IP cases were 28-52 years old, of Latino origin, and 62.5% female. Onset dates ranged from April 2005-December 2007; 60% were hospitalized. IP cases at this plant were similar in clinical presentation and exposure risks to those detected in Minnesota. Swine abattoirs using similar brain extraction methods should discontinue this process.",
"title": "A clustering of immune-mediated polyradiculoneuropathy among swine abattoir workers exposed to aerosolized porcine brains, Indiana, United States."
},
{
"docid": "MED-2644",
"text": "Alkylphenols are widely used as plastic additives and surfactants. We report the identification of an alkylphenol, nonylphenol, as an estrogenic substance released from plastic centrifuge tubes. This compound was extracted with methanol, purified by flash chromatography and reverse-phase high performance liquid chromatography, and identified by gas chromatography-mass spectrometry. Nonylphenol induced both cell proliferation and progesterone receptor in human estrogen-sensitive MCF7 breast tumor cells. Nonylphenol also triggered mitotic activity in rat endometrium; this result confirms the reliability of the MCF7 cell proliferation bioassay. The estrogenic properties of alkylphenols, specifically nonylphenols, indicate that the use of plasticware containing these chemicals in experimental and diagnostic tests may lead to spurious results, and these compounds as well as alkylphenol polyethoxylates may also be potentially harmful to exposed humans and the environment at large.",
"title": "p-Nonyl-phenol: an estrogenic xenobiotic released from \"modified\" polystyrene."
},
{
"docid": "MED-2210",
"text": "We investigated the effects of sporamin, the major soluble protein with a kunitz-type trypsin inhibitory activity in the root tuber of the sweet potato, on cell proliferation, apoptosis, Akt/GSK-3 signaling and its related genes to provide more insights in the mechanism behind the inhibitory effects of sporamin in a human tongue cancer line Tca8113. In this study, sporamin inhibited cell proliferation and induced apoptosis in Tca8113 cells in a concentration-dependent and time-dependent manner. Consistently, Bax was up-regulated and Bcl-2 was down-regulated in sporamin-treated cells. Furthermore, Akt/GSK-3 signaling was down-regulated in sporamin-treated cells. Consistently, the phosphorylated Bad was significantly declined in sporamin-treated Tca8113 cells. These results suggest the antiproliferative effects of sporamin in Tca8113 cells might result partly from induction of apoptosis by down-regulating Akt/GSK-3 pathway. © 2010 The Authors Fundamental and Clinical Pharmacology © 2010 Société Française de Pharmacologie et de Thérapeutique.",
"title": "Sporamin induce apoptosis in human tongue carcinoma cells by down-regulating Akt/GSK-3 signaling."
},
{
"docid": "MED-2652",
"text": "The exposure to some chemicals can lead to hormone disrupting effects. Presently, much attention is focused on so-called xeno-estrogens, synthetic compounds that interact with hormone receptors causing a number of reactions that eventually lead to effects related to reproduction and development. The current study was initiated to investigate the presence of a number of such compounds in precipitation as a follow-up on a previous study in which pesticide concentrations in air and precipitation were determined. Rainwater samples were collected at about 50 locations in The Netherlands in a four week period. The samples were analysed for bisphenol-A, alkylphenols and alkylphenol ethoxylates, phthalates, flame retardants and synthetic musk compounds. The results clearly indicated the presence of these compounds in precipitation. The concentrations ranged from the low ng l(-1) range for flame retardants to several thousands of ng l(-1) for the phthalates. Bisphenol-A was found in 30% of the samples in concentrations up to 130 ng l(-1), while alkylphenols and alkylphenol ethoxylates were found in virtually all locations in concentrations up to 920 ng l(-1) for the individual compounds. Phthalates were by far the most abundant xeno-estrogens in the precipitation samples and were found in every sample. Di-isodecyl phthalate was found in a surprisingly high concentration of almost 100 000 ng l(-1). Polybrominated flame retardants were found in the low ng l(-1) range and generally in less than 20% of the samples. Noticeable was the finding of hexabromocyclododecane, a replacement for the polybrominted diphenyl ethers at one location in a concentration of almost 2000 ng l(-1). Finally, as expected, synthetic musk compounds were detected in almost all samples. This is especially true for the polycyclic musks HHCB and AHTN. Nitro musks were found, but only on a few locations. Kriging techniques were used to calculate precipitation concentrations in between actual sampling locations to produce contour plots for a number of compounds. These plots clearly show located emission sources for a number of compounds such as bisphenol-A, nonylphenol ethoxylate, phthalates and AHTN. On the contrary, the results for HHCB and some phthalates indicated diffuse emission patterns, probably as the result of the use of consumer products containing these compounds.",
"title": "Xeno-estrogenic compounds in precipitation."
},
{
"docid": "MED-4954",
"text": "BACKGROUND To look at possible long-term risks from anabolic steroids and other xenobiotics in beef, we examined men's semen quality in relation to their mother's self-reported beef consumption during pregnancy. METHODS: The study was carried out in five US cities between 1999 and 2005. We used regression analyses to examine semen parameters in 387 partners of pregnant women in relation to the amount of beef their mothers reported eating while pregnant. Mothers' beef consumption was also analysed in relation to the son's history of previous subfertility. RESULTS Sperm concentration was inversely related to mothers' beef meals per week (P = 0.041). In sons of \"high beef consumers\" (>7 beef meals/week), sperm concentration was 24.3% lower (P = 0.014) and the proportion of men with sperm concentration below 20 x 10(6)/ml was three times higher (17.7 versus 5.7%, P = 0.002) than in men whose mothers ate less beef. A history of previous subfertility was also more frequent among sons of \"high beef consumers\" (P = 0.015). Sperm concentration was not significantly related to mother's consumption of other meat or to the man's consumption of any meat. CONCLUSIONS These data suggest that maternal beef consumption, and possibly xenobiotics in beef, may alter a man's testicular development in utero and adversely affect his reproductive capacity.",
"title": "Semen quality of fertile US males in relation to their mothers' beef consumption during pregnancy."
},
{
"docid": "MED-1253",
"text": "OBJECTIVES: To investigate the effect of replacing lean meat with a soy product, tofu, on serum lipoprotein concentrations. STUDY AND DESIGN: Randomized cross-over dietary intervention study. SUBJECTS: Forty-two free-living healthy males aged 35-62 y completed the dietary intervention. Three additional subjects were non-compliant and excluded prior to analysis. INTERVENTIONS: A diet containing lean meat (150 g/d) was compared with one with 290 g/d tofu in an isocaloric and isoprotein substitution. Both diet periods were 1 month, and fat intake was carefully controlled. RESULTS: Seven-day diet records showed the two diets were similar in energy, macronutrients and fibre. Total cholesterol (mean difference 0.23 mmol/l, 95% CI 0.02, 0.43; P=0.03) and triglycerides (mean difference 0.15 mmol/l, 95% CI 0.02, 0.31; P=0.017) were significantly lower on the tofu diet than the lean meat diet. However, HDL-C was also significantly lower on the tofu diet (mean difference 0.08 mmol/l, 95% CI 0.02, 0.14; P=0.01) although the LDL-C:HDL-C ratio was similar. CONCLUSION: The effect on HDL-C and the small LDL-C reduction differ from some other studies, where fat was often less controlled, and the comparison was of soy as textured protein or soymilk against casein. This suggests a differential effect of the various proteins compared to the soy may influence the findings. In practice, the replacement of meat with tofu would usually be associated with a decrease in saturated fat and an increase in polyunsaturated fat and this should enhance any small benefits due to the soy protein. SPONSOR: Deakin University with some contribution from a Commonwealth Department of Veterans Affairs research grant. European Journal of Clinical Nutrition (2000) 54, 14-19",
"title": "Effects of soy as tofu vs meat on lipoprotein concentrations."
},
{
"docid": "MED-3784",
"text": "Dietary choline and betaine have been hypothesized to decrease the risk of cancer because of their role as methyl donors in the one-carbon metabolism. However, it remains unknown whether dietary intake of choline and betaine is associated with colorectal cancer risk. We prospectively examined the associations between dietary choline and betaine intake and risk of colorectal cancer in men in the Health Professionals Follow-up Study. We followed 47,302 men and identified a total of 987 incident colorectal cancer cases from 1986 to 2004. We assessed dietary and supplemental choline and betaine intake every four years using a validated semi-quantitative food frequency questionnaire. The Cox proportional hazards model was used to estimate multivariate relative risks (RRs) and 95% confidence intervals (95% CIs). All statistical tests were two-sided. We did not find any statistically significant associations between choline intake or betaine intake and risk of colorectal cancer. Comparing the top quintile with bottom quintile, multivariate RRs (95% CI) were 0.97 (0.79-1.20; Ptrend = 0.87) for choline intake and 0.94 (0.77-1.16; Ptrend = 0.79) for betaine intake. Similarly, we observed no associations between colorectal cancer risk and choline from free choline, glycerophosphocholine, phosphocholine, phosphatidylcholine, or sphingomyelin. Our data do not support that choline and betaine intake is inversely associated with colorectal cancer risk.",
"title": "Choline and betaine intake and the risk of colorectal cancer in men"
},
{
"docid": "MED-1252",
"text": "The effect of substituting soy for animal protein in mixed diets was determined in young men with mildly elevated plasma cholesterol, 218 to 307 mg/dl. The diets were low in cholesterol, 200 mg/day, with 13 to 16% of energy as protein, 30 to 35% as fat, and a polyunsaturated to saturated fat ratio of 0.5. Of protein 65% was from either mixed animal proteins or isolated soy protein products made comparable by the addition of extracted animal fats. Fresh egg yolk was added to balance the cholesterol content of the diets. Proteins from grains and vegetables were identical in both menus and contributed about 35% of dietary protein. Twenty of 24 subjects decreased plasma cholesterol at the end of the protocol. Subjects were classified as responders or nonresponders as a function of greater or lesser than mean reduction in cholesterol for the groups. Mean decreases in plasma cholesterol, 16 and 13%, for responders in the animal and soy groups were significant, p less than 0.01 and 0.05, respectively. Responders in both groups had higher initial plasma cholesterol values than nonresponders. Although plasma high-density lipoprotein cholesterol decreased slightly, the high-density lipoprotein cholesterol to cholesterol ratio (high-density lipoprotein cholesterol/total cholesterol) remained constant for most individuals. The hypocholesterolemic effects were similar for both animal and soy protein (p less than 0.05) and fat (p less than 0.05) while on the experimental diet. All groups significantly decreased dietary cholesterol (p less than 0.001).",
"title": "Determinants of hypocholesterolemic response to soy and animal protein-based diets."
},
{
"docid": "MED-3220",
"text": "Background Maintaining muscle mass while aging is important to prevent falls and fractures. Metabolic acidosis promotes muscle wasting, and the net acid load from diets that are rich in net acid–producing protein and cereal grains relative to their content of net alkali–producing fruit and vegetables may therefore contribute to a reduction in lean tissue mass in older adults. Objective We aimed to determine whether there was an association of 24-h urinary potassium and an index of fruit and vegetable content of the diet with the percentage lean body mass (%LBM) or change in %LBM in older subjects. Design Subjects were 384 men and women ≥65 y old who participated in a 3-y trial comparing calcium and vitamin D with placebo. Potassium was measured in 24-h urine collections at baseline. The %LBM, defined as total body nonfat, nonbone tissue weight ÷ weight × 100, was measured by using dual-energy X-ray absorptiometry at baseline and at 3 y. Physical activity, height, and weight were assessed at baseline and at 3 y. Results At baseline, the mean urinary potassium excretion was 67.0 ± 21.1 mmol/d. Urinary potassium (mmol/d) was significantly positively associated with %LBM at baseline (β = 0.033, P = 0.006; adjusted for sex, weight, and nitrogen excretion) but not with 3-y change in %LBM. Over the 3-y study, %LBM increased by 2.6 ± 3.6%. Conclusion Higher intake of foods rich in potassium, such as fruit and vegetables, may favor the preservation of muscle mass in older men and women.",
"title": "Alkaline diets favor lean tissue mass in older adults"
},
{
"docid": "MED-3878",
"text": "Diet, nutritional status, and certain dietary supplements are postulated to influence the development and progression of prostate cancer. Angiogenesis and inflammation are central to tumor growth and progression, but the effect of diet on these processes remains uncertain. We explored changes in 50 plasma cytokines and angiogenic factors (CAFs) in 145 men with prostate cancer enrolled in a pre-operative, randomized controlled phase-II trial with four arms: control (usual diet); low-fat (LF) diet; flaxseed-supplemented (FS) diet; and flaxseed-supplemented, low-fat diet. The mean duration of dietary intervention was 30–31 days. Among the individual arms, the largest number of significant changes (baseline vs pre-operative follow-up) was observed in the LF arm, with 19 CAFs decreasing and one increasing (p<.05). Compared to the control arm, 6 CAFs—including pro-angiogenic factors (stromal-cell derived-1α and myeloid factors (granulocyte-colony-stimulating factor, macrophage colony-stimulating factor — all decreased in the LF arm compared to controls; 3 and 4 CAFs changed in the FS and FS+LF arms, respectively. Weight loss occurred in the LF arms and significantly correlated with VEGF decreases (P <0.001). The CAFs that changed in the LF arm are all known to be regulated by nuclear factor-kappa B (NF-κB), and a pathway analysis identified NF-κB as the most likely regulatory network associated with these changes in the LF arm, but not in the FS-containing arms. These results suggest that a low-fat diet without flaxseed may reduce levels of specific inflammatory cytokines and angiogenic factors and suggests that the NF-κB pathway may be a mediator of these changes.",
"title": "Effect of Low-fat Diets on Plasma Levels of NFκB-regulated Inflammatory Cytokines and Angiogenic Factors in Men with Prostate Cancer"
},
{
"docid": "MED-2452",
"text": "A role for diet in the pathophysiology of asthma may be mediated by altered immune or antioxidant activity with consequent effects on airway inflammation. We evaluated associations between several dietary factors assessed by a semiquantitative food frequency questionnaire, and incidence of asthma over a 10-yr period in 77,866 women 34 to 68 yr of age. Women in the highest quintile of vitamin E intake from diet, but not from supplements, had a risk of 0.53 (95% confidence interval [CI] = 0.33 to 0.86) compared with women in the lowest quintile. This relationship, however, was attenuated when the contribution from nuts, a major source of vitamin E in these data and a possible allergen, was removed (relative risk = 0.74 [0.50 to 1.10], p for trend = 0.007). Positive associations were found for vitamins C and E from supplements, but appeared to be explained by women at high risk of asthma initiating use of vitamin supplements prior to diagnosis. A nonsignificant inverse association with carotene intake was noted, but no clear relations with asthma were demonstrated for intake of linoleic acid or omega-3 fatty acids. These data suggest that antioxidant supplementation and intake of various fats during adulthood are not important determinants of asthma, although vitamin E from diet may have a modest protective effect.",
"title": "A prospective study of diet and adult-onset asthma."
},
{
"docid": "MED-2126",
"text": "Increased protein supply by feeding cow-milk-based infant formula in comparison to lower protein content of human milk is a well-recognized major risk factor of childhood obesity. However, there is yet no conclusive biochemical concept explaining the mechanisms of formula-induced childhood obesity. It is the intention of this article to provide the biochemical link between leucine-mediated signalling of mammalian milk proteins and adipogenesis as well as early adipogenic programming. Leucine has been identified as the predominant signal transducer of mammalian milk, which stimulates the nutrient-sensitive kinase mammalian target of rapamycin complex 1 (mTORC1). Leucine thus functions as a maternal-neonatal relay for mTORC1-dependent neonatal β-cell proliferation and insulin secretion. The mTORC1 target S6K1 plays a pivotal role in stimulation of mesenchymal stem cells to differentiate into adipocytes and to induce insulin resistance. It is of most critical concern that infant formulas provide higher amounts of leucine in comparison to human milk. Exaggerated leucine-mediated mTORC1-S6K1 signalling induced by infant formulas may thus explain increased adipogenesis and generation of lifelong elevated adipocyte numbers. Attenuation of mTORC1 signalling of infant formula by leucine restriction to physiologic lower levels of human milk offers a great chance for the prevention of childhood obesity and obesity-related metabolic diseases.",
"title": "Excessive Leucine-mTORC1-Signalling of Cow Milk-Based Infant Formula: The Missing Link to Understand Early Childhood Obesity"
},
{
"docid": "MED-4060",
"text": "Heteroyclic aromatic amines (HAAs) are a class of hazardous chemicals that are receiving heightened attention as a risk factor for human cancer. HAAs arise during the cooking of meats, fish, and poultry, and several HAAs also occur in tobacco smoke condensate and diesel exhaust. Many HAAs are carcinogenic and induce tumors at multiple sites in rodents. A number of epidemiologic studies have reported that frequent consumption of well-done cooked meats containing HAAs can result in elevated risks for colon, prostate, and mammary cancers. Moreover, DNA adducts of HAAs have been detected in human tissues, demonstrating that HAAs induce genetic damage even though the concentrations of these compounds in cooked meats are generally in the low parts-per-billion (ppb) range. With recent improvements in sensitivity of mass spectrometry instrumentation, HAAs, their metabolites, and DNA adducts can be detected at trace amounts in biological fluids and tissues of humans. The incorporation of HAA biomarkers in epidemologic studies will help to clarify the role of these dietary genotoxicants in the etiology of human cancer.",
"title": "Formation and biochemistry of carcinogenic heterocyclic aromatic amines in cooked meats."
},
{
"docid": "MED-2332",
"text": "Plants have evolved a variety of responses to elevated temperatures that minimize damage and ensure protection of cellular homeostasis. New information about the structure and function of heat stress proteins and molecular chaperones has become available. At the same time, transcriptome analysis of Arabidopsis has revealed the involvement of factors other than classical heat stress responsive genes in thermotolerance. Recent reports suggest that both plant hormones and reactive oxygen species also contribute to heat stress signaling. Additionally, an increasing number of mutants that have altered thermotolerance have extended our understanding of the complexity of the heat stress response in plants.",
"title": "Complexity of the heat stress response in plants."
},
{
"docid": "MED-2333",
"text": "Until recently, the study and understanding of plant and animal signalling and response mechanisms have developed independently. Recent biochemical and molecular work is producing a growing list of elements involved in responses to biotic and abiotic stimuli that are very similar across kingdoms. Some of the more interesting examples of these include prostaglandin/octadecanoid-mediated responses to wounding, steroid-based signalling systems, and pathogen-recognition mechanisms. Some of these similarities probably represent evolutionary convergence; others may be ancestral to plants and animals. Ecological and evolutionary implications of such overlaps include the existence of pathogens that can cause disease in plants and animals, the ability of herbivores to manipulate plant responses, usurpation of microbial mechanisms and genes by herbivorous animals and plants, evolution of plant defenses exploiting shared signals in animals, and the medicinal use of plants by humans. Comparative study of the signalling and response mechanisms used by plants, animals, and microbes provides novel and useful insights to the ecology and evolution of interactions across kingdoms.",
"title": "Shared signals and the potential for phylogenetic espionage between plants and animals."
},
{
"docid": "MED-3450",
"text": "Although assays for the most popular markers of exercise-induced oxidative stress may experience methodological flaws, there is sufficient credible evidence to suggest that exercise is accompanied by an increased generation of free radicals, resulting in a measurable degree of oxidative modifications to various molecules. However, the mechanisms responsible are unclear. A common assumption that increased mitochondrial oxygen consumption leads per se to increased reactive oxygen species (ROS) production is not supported by in vitro and in vivo data. The specific contributions of other systems (xanthine oxidase, inflammation, haem protein auto-oxidation) are poorly characterised. It has been demonstrated that ROS have the capacity to contribute to the development of muscle fatigue in situ, but there is still a lack of convincing direct evidence that ROS impair exercise performance in vivo in humans. It remains unclear whether exercise-induced oxidative modifications have little significance, induce harmful oxidative damage, or are an integral part of redox regulation. It is clear that ROS play important roles in numerous physiological processes at rest; however, the detailed physiological functions of ROS in exercise remain to be elucidated.",
"title": "Exercise-induced oxidative stress:myths, realities and physiological relevance."
},
{
"docid": "MED-4040",
"text": "The consumption of cooked meat appears to predispose individuals to colonic cancer and heterocyclic aromatic amines (HA), formed during the cooking of meat, have been suggested as aetiological agents. Consumption of cruciferous vegetables is thought to protect against cancer. To study the effect of cruciferous vegetables on heterocyclic aromatic amine metabolism in man, a three-period, dietary intervention study has been carried out with 20 non-smoking Caucasian male subjects consuming cooked meat meals containing known amounts of these carcinogens. A high cruciferous vegetable diet (250 g each of Brussels sprouts and broccoli per day) was maintained during period 2 but such vegetables were excluded from periods 1 and 3. At the end of each period, subjects consumed a cooked meat meal and urinary excretion of the HA 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) was measured. Following a 12 day period of cruciferous vegetable consumption (period 2), induction of hepatic CYP1A2 activity was apparent from changes in the kinetics of caffeine metabolism. Excretion of MeIQx and PhIP in urine at the end of this period of the study was reduced by 23 and 21%, respectively, compared with period 1. This reduction in excretion is probably due to an increase in amine metabolism that might be expected given the observed increase in CYP1A2 activity, since this enzyme has been shown to be primarily responsible for the oxidative activation of MeIQx and PhIP in man. In period 2, urinary mutagenicity was increased relative to period 1 by 52 and 64% in the absence and presence, respectively, of a human liver microsomal activation system, yet no evidence was found of PhIP adduction to lymphocyte DNA, a potential biomarker of the activation process. After another 12 days without cruciferous vegetables (period 3 of the study), the kinetics of caffeine metabolism had returned to original values but excretion of MeIQx and PhIP was still reduced by 17 and 30%, respectively, and urinary mutagenicity (with metabolic activation) was still elevated compared with period 1. This prolonged response of amine metabolism to the cruciferous vegetable diet, shown especially with PhIP, suggests that enzyme systems other than CYP1A2 are involved and affected by a cruciferous vegetable diet.",
"title": "Effect of cruciferous vegetable consumption on heterocyclic aromatic amine metabolism in man."
},
{
"docid": "MED-2479",
"text": "BACKGROUND: The prevalence of allergic diseases seems to have increased particularly over the past 35-40 years. Furthermore, allergic disease is less common among children in the formerly socialist countries of central and Eastern Europe as compared with Western Europe. It has been suggested that a reduced microbial stimulation during infancy and early childhood would result in a slower postnatal maturation of the immune system and development of an optimal balance between TH1- and TH2-like immunity. AIMS: To test the hypothesis that allergic disease among children may be associated with differences in their intestinal microflora in two countries with a low (Estonia) and a high (Sweden) prevalence of allergy. METHODS: From a prospective study of the development of allergy in relation to environmental factors, 29 Estonian and 33 Swedish 2-year-old children were selected. They were either nonallergic (n = 36) or had a confirmed diagnosis of allergy (n = 27) as verified by typical history and at least one positive skin prick test to egg or cow's milk. Weighed samples of faeces were serially diluted (10-2-10-9) and grown under anaerobic conditions. The counts of the various genera and species were calculated for each child. In addition, the relative amounts of the particular microbes were expressed as a proportion of the total count. RESULTS: The allergic children in Estonia and Sweden were less often colonized with lactobacilli (P < 0.01), as compared with the nonallergic children in the two countries. In contrast, the allergic children harboured higher counts of aerobic micro-organisms (P < 0. 05), particularly coliforms (P < 0.01) and Staphylococcus aureus (P < 0.05). The proportions of aerobic bacteria of the intestinal flora were also higher in the allergic children (P < 0.05), while the opposite was true for anaerobes (P < 0.05). Similarly, in the allergic children the proportions of coliforms were higher (P < 0. 05) and bacteroides lower (P < 0.05) than in the nonallergic children. CONCLUSIONS: Differences in the indigenous intestinal flora might affect the development and priming of the immune system in early childhood, similar to what has been shown in rodents. The role of intestinal microflora in relation to the development of infant immunity and the possible consequences for allergic diseases later in life requires further study, particularly as it would be readily available for intervention as a means for primary prevention of allergy by the administration of probiotic bacteria.",
"title": "The intestinal microflora in allergic Estonian and Swedish 2-year-old children."
},
{
"docid": "MED-1718",
"text": "The number of cancer cases caused by being obese is estimated to be 20% with the increased risk of malignancies being influenced by diet, weight change, and body fat distribution together with physical activity. Reports from the International Agency for Research into Cancer and the World Cancer Research Fund (WCRF) have shown that the strongest evidence exists for an association of obesity with the following cancer types: endometrial, esophageal adenocarcinoma, colorectal, postmenopausal breast, prostate, and renal, whereas the less common malignancies are leukemia, non-Hodgkin's lymphoma, multiple myeloma, malignant melanoma, and thyroid tumours. To be able to develop novel methods in prevention and treatment, we first must understand the underlying processes which link cancer to obesity. Four main systems have been identified as potential producers of cancer in obesity: insulin, insulin-like growth factor-I, sex steroids, and adipokines. Various novel candidate mechanisms have been proposed: chronic inflammation, oxidative stress, crosstalk between tumour cells and surrounding adipocytes, migrating adipose stromal cells, obesity-induced hypoxia, shared genetic susceptibility, and the functional defeat of immune function. Herein, we review the major pathogenic links between obesity and susceptibility to cancer.",
"title": "Obesity as a Major Risk Factor for Cancer"
},
{
"docid": "MED-1717",
"text": "BACKGROUND: Excess bodyweight, expressed as increased body-mass index (BMI), is associated with the risk of some common adult cancers. We did a systematic review and meta-analysis to assess the strength of associations between BMI and different sites of cancer and to investigate differences in these associations between sex and ethnic groups. METHODS: We did electronic searches on Medline and Embase (1966 to November 2007), and searched reports to identify prospective studies of incident cases of 20 cancer types. We did random-effects meta-analyses and meta-regressions of study-specific incremental estimates to determine the risk of cancer associated with a 5 kg/m2 increase in BMI. FINDINGS: We analysed 221 datasets (141 articles), including 282,137 incident cases. In men, a 5 kg/m2 increase in BMI was strongly associated with oesophageal adenocarcinoma (RR 1.52, p<0.0001) and with thyroid (1.33, p=0.02), colon (1.24, p<0.0001), and renal (1.24, p <0.0001) cancers. In women, we recorded strong associations between a 5 kg/m2 increase in BMI and endometrial (1.59, p<0.0001), gallbladder (1.59, p=0.04), oesophageal adenocarcinoma (1.51, p<0.0001), and renal (1.34, p<0.0001) cancers. We noted weaker positive associations (RR <1.20) between increased BMI and rectal cancer and malignant melanoma in men; postmenopausal breast, pancreatic, thyroid, and colon cancers in women; and leukaemia, multiple myeloma, and non-Hodgkin lymphoma in both sexes. Associations were stronger in men than in women for colon (p<0.0001) cancer. Associations were generally similar in studies from North America, Europe and Australia, and the Asia-Pacific region, but we recorded stronger associations in Asia-Pacific populations between increased BMI and premenopausal (p=0.009) and postmenopausal (p=0.06) breast cancers. INTERPRETATION: Increased BMI is associated with increased risk of common and less common malignancies. For some cancer types, associations differ between sexes and populations of different ethnic origins. These epidemiological observations should inform the exploration of biological mechanisms that link obesity with cancer.",
"title": "Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies."
},
{
"docid": "MED-3228",
"text": "A precise understanding of the role of dietary protein in bone health has been evasive despite decades of research. It is known that a dietary acid load is harmful to bone, and sulfur-containing amino acids are metabolized to provide such an acid load. It is also known that protein elevates urine calcium loss. However, recent clinical studies and a meta-analysis have indicated either no effect or a modest benefit associated with higher protein intakes. These contradictory considerations may be explained by the existence of a two-faced relationship between protein and bone, with simultaneous positive and negative pathways. In opposition to the negative effects of dietary acid load, protein may exert positive effects related to improving calcium absorption, increasing insulin-like growth factor 1, or improving lean body mass, which, in turn, improves bone strength. Putative mechanisms behind these pathways are reviewed here, and some limitations in the historical literature as well as suggested measures to counter these in the future are identified. When positive and negative pathways are considered in tandem, protein may offer modest benefits to bone in the presence of adequate dietary calcium and acid-neutralizing fruits and vegetables. © 2011 International Life Sciences Institute.",
"title": "Dietary protein and bone health: harmonizing conflicting theories."
},
{
"docid": "MED-3318",
"text": "Smoking is an established risk factor for pancreatic cancer; however, detailed examination of the association of smoking intensity, smoking duration, and cumulative smoking dose with pancreatic cancer is limited. The authors analyzed pooled data from the international Pancreatic Cancer Cohort Consortium nested case-control study (1,481 cases, 1,539 controls). Odds ratios and 95% confidence intervals were calculated by using unconditional logistic regression. Smoking intensity effects were examined with an excess odds ratio model that was linear in pack-years and exponential in cigarettes smoked per day and its square. When compared with never smokers, current smokers had a significantly elevated risk (odds ratio (OR) = 1.77, 95% confidence interval (CI): 1.38, 2.26). Risk increased significantly with greater intensity (≥30 cigarettes/day: OR = 1.75, 95% CI: 1.27, 2.42), duration (≥50 years: OR = 2.13, 95% CI: 1.25, 3.62), and cumulative smoking dose (≥40 pack-years: OR = 1.78, 95% CI: 1.35, 2.34). Risk more than 15 years after smoking cessation was similar to that for never smokers. Estimates of excess odds ratio per pack-year declined with increasing intensity, suggesting greater risk for total exposure delivered at lower intensity for longer duration than for higher intensity for shorter duration. This finding and the decline in risk after smoking cessation suggest that smoking has a late-stage effect on pancreatic carcinogenesis.",
"title": "Cigarette Smoking and Pancreatic Cancer: A Pooled Analysis From the Pancreatic Cancer Cohort Consortium"
},
{
"docid": "MED-2207",
"text": "The objective of this study was to investigate the antiproliferative effect and the mechanism of trypsin inhibitor (TI) from sweet potato [Ipomoea batatas (L.) Lam. 'Tainong 57'] storage roots on NB4 promyelocytic leukemia cells. The results showed that TI inhibited cellular growth of NB4 promyelocytic leukemia cells in a time-dependent and dose-dependent manner, and treatment for 72 h induced a marked inhibition of cellular growth, showing an IC50 of 57.1 +/- 8.26 microg/mL. TI caused cell cycle arrest at the G1 phase as determined by flow cytometric analysis and apoptosis as shown by DNA laddering. TI-induced cell apoptosis involved p53, Bcl-2, Bax, and cytochrome c protein in NB4 cells. P53 and Bax proteins were accumulated, and antiapoptotic molecule Bcl-2 was decreased in the tested cells in a time-dependent manner during TI treatment. TI also induced a substantial release of cytochrome c from the mitochondria into the cytosol. Hence, TI induced apoptosis in NB4 cells through a mitochondria-dependent pathway, which was associated with the activation of caspase-3 and -8. These results demonstrated that TI induces NB4 cell apoptosis through the inhibition of cell growth and the activation of the pathway of caspase-3 and -8 cascades.",
"title": "Growth inhibition and induction of apoptosis in NB4 promyelocytic leukemia cells by trypsin inhibitor from sweet potato storage roots."
},
{
"docid": "MED-1186",
"text": "We investigated the effect of resistant starch (RS) on markers of colonic protein metabolism. Eleven subjects participated in a randomized crossover study in which they consumed either high-RS (39 +/- 3 g/d, -chi +/- SEM) or low-RS (5 +/- 0.4 g/d) diets for 3 wk. All other macronutrients were kept constant. During the high-RS diet daily excretion of fecal nitrogen increased from 1.84 +/- 0.15 to 2.86 +/- 0.42 g/d (P < 0.01) and excretion of fecal phenols fell from 9.2 +/- 1.4 to 5.3 +/- 0.8 mg/d (P < 0.01). Fecal concentrations of ammonia decreased from 397 +/- 33 to 278 +/- 49 microgram/g (P < 0.01) and phenols decreased from 69 +/- 8 to 39 +/- 10 microgram/g (P < 0.001). Daily output of urinary ammonia, urea, phenols, and total nitrogen did not change significantly, but pH decreased from 6.4 +/- 0.1 to 6.2 +/- 0.1 (P < 0.05) during the high-RS period. These results suggest that RS significantly attenuates the accumulation of potentially harmful byproducts of protein fermentation in the human colon.",
"title": "Resistant starch lowers fecal concentrations of ammonia and phenols in humans."
},
{
"docid": "MED-3279",
"text": "Various pesticides are being used to destabilize, perturb, or inhibit crucial biochemical and physiological targets related to metabolism, growth, development, nervous communication, or behavior in pestiferous organisms. Chitin is an eukaryotic extracellular aminosugar biopolymer, massively produced by most fungal systems and by invertebrates, notably arthropods. Being an integral supportive component in fungal cell wall, insect cuticle, and nematode egg shell, chitin has been considered as a selective target for pesticide action. Throughout the elaborate processes of chitin formation and deposition, only the polymerization events associated with the cell membrane compartment are so far available for chemical interference. Currently, the actinomycetes-derived nucleoside peptide fungicides such as the polyoxins and the insecticidal benzoylaryl ureas have reached commercial pesticide status. The polyoxins and other structurally-related antibiotics like nikkomycins are strong competitive inhibitors of the polymerizing enzyme chitin synthase. The exact biochemical lesion inflicted by the benzoylaryl ureas is still elusive, but a post-polymerization event, such as translocation of chitin chains across the cell membrane, is suggested. Hydrolytic degradation of the chitin polymer is essential for hyphal growth, branching, and septum formation in fungal systems as well as for the normal molting of arthropods. Recently, insect chitinase activity was strongly and specifically suppressed by allosamidin, an actimomycetes-derived metabolite. In part, the defense mechanism in plants against invasion of pathogens is associated with induced chitinases. Chitin, chitosan, and their oligomers are able to act as elicitors which induce enhanced levels of chitinases in various plants. Lectins which bind to N-acetyl-D-glucosamine strongly interfere with fungal and insect chitin synthases. Plant lectins with similar properties may be involved in plant-pathogen interaction inter alia by suppressing fungal invasion.",
"title": "Chitin synthesis and degradation as targets for pesticide action."
},
{
"docid": "MED-4233",
"text": "OBJECTIVES: Dietary fat and fiber affect hormonal levels and may influence cancer progression. Flaxseed is a rich source of lignan and omega-3 fatty acids and may thwart prostate cancer. The potential effects of flaxseed may be enhanced with concomitant fat restriction. We undertook a pilot study to explore whether a flaxseed-supplemented, fat-restricted diet could affect the biomarkers of prostatic neoplasia. METHODS: Twenty-five patients with prostate cancer who were awaiting prostatectomy were instructed on a low-fat (20% of kilocalories or less), flaxseed-supplemented (30 g/day) diet. The baseline and follow-up levels of prostate-specific antigen, testosterone, free androgen index, and total serum cholesterol were determined. The tumors of diet-treated patients were compared with those of historic cases (matched by age, race, prostate-specific antigen level at diagnosis, and biopsy Gleason sum) with respect to apoptosis (terminal deoxynucleotidyl transferase [TdT]-mediated dUTP-biotin nick end-labeling [TUNEL]) and proliferation (MIB-1). RESULTS: The average duration on the diet was 34 days (range 21 to 77), during which time significant decreases were observed in total serum cholesterol (201 +/- 39 mg/dL to 174 +/- 42 mg/dL), total testosterone (422 +/- 122 ng/dL to 360 +/- 128 ng/dL), and free androgen index (36.3% +/- 18.9% to 29.3% +/- 16.8%) (all P <0.05). The baseline and follow-up levels of prostate-specific antigen were 8.1 +/- 5.2 ng/mL and 8.5 +/- 7.7 ng/mL, respectively, for the entire sample (P = 0.58); however, among men with Gleason sums of 6 or less (n = 19), the PSA values were 7.1 +/- 3.9 ng/mL and 6.4 +/- 4.1 ng/mL (P = 0.10). The mean proliferation index was 7.4 +/- 7.8 for the historic controls versus 5.0 +/- 4.9 for the diet-treated patients (P = 0.05). The distribution of the apoptotic indexes differed significantly (P = 0.01) between groups, with most historic controls exhibiting TUNEL categorical scores of 0; diet-treated patients largely exhibited scores of 1. Both the proliferation rate and apoptosis were significantly associated with the number of days on the diet (P = 0.049 and P = 0.017, respectively). CONCLUSIONS: These pilot data suggest that a flaxseed-supplemented, fat-restricted diet may affect prostate cancer biology and associated biomarkers. Further study is needed to determine the benefit of this dietary regimen as either a complementary or preventive therapy.",
"title": "Pilot study of dietary fat restriction and flaxseed supplementation in men with prostate cancer before surgery: exploring the effects on hormonal l..."
},
{
"docid": "MED-3237",
"text": "The modern Western-type diet is deficient in fruits and vegetables and contains excessive animal products, generating the accumulation of non-metabolizable anions and a lifespan state of overlooked metabolic acidosis, whose magnitude increases progressively with aging due to the physiological decline in kidney function. In response to this state of diet-derived metabolic acidosis, the kidney implements compensating mechanisms aimed to restore the acid-base balance, such as the removal of the non-metabolizable anions, the conservation of citrate, and the enhancement of kidney ammoniagenesis and urinary excretion of ammonium ions. These adaptive processes lower the urine pH and induce an extensive change in urine composition, including hypocitraturia, hypercalciuria, and nitrogen and phosphate wasting. Low urine pH predisposes to uric acid stone formation. Hypocitraturia and hypercalciuria are risk factors for calcium stone disease. Even a very mild degree of metabolic acidosis induces skeletal muscle resistance to the insulin action and dietary acid load may be an important variable in predicting the metabolic abnormalities and the cardiovascular risk of the general population, the overweight and obese persons, and other patient populations including diabetes and chronic kidney failure. High dietary acid load is more likely to result in diabetes and systemic hypertension and may increase the cardiovascular risk. Results of recent observational studies confirm an association between insulin resistance and metabolic acidosis markers, including low serum bicarbonate, high serum anion gap, hypocitraturia, and low urine pH. Copyright © 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.",
"title": "Diet-induced metabolic acidosis."
},
{
"docid": "MED-5116",
"text": "BACKGROUND: Laboratory research and a growing number of epidemiologic studies have provided evidence for a reduced risk of breast cancer associated with dietary intake of certain classes of flavonoids. However, the effects of flavonoids on survival are not known. In a population-based cohort of breast cancer patients, we investigated whether dietary flavonoid intake before diagnosis is associated with subsequent survival. METHODS: Women ages 25 to 98 years who were newly diagnosed with a first primary invasive breast cancer between August 1, 1996, and July 31, 1997, and participated in a population-based, case-control study (n=1,210) were followed for vital status through December 31, 2002. At the case-control interview conducted shortly after diagnosis, respondents completed a FFQ that assessed dietary intake in the previous 12 months. All-cause mortality (n=173 deaths) and breast cancer-specific mortality (n=113 deaths) were determined through the National Death Index. RESULTS: Reduced hazard ratios [age- and energy-adjusted hazard ratio (95% confidence interval)] for all-cause mortality were observed among premenopausal and postmenopausal women for the highest quintile of intake, compared with the lowest, for flavones [0.63 (0.41-0.96)], isoflavones [0.52 (0.33-0.82)], and anthocyanidins [0.64 (0.42-0.98)]. No significant trends in risk were observed. Results were similar for breast cancer-specific mortality only. CONCLUSION: Mortality may be reduced in association with high levels of dietary flavones and isoflavones among postmenopausal U.S. breast cancer patients. Larger studies are needed to confirm our findings.",
"title": "Dietary flavonoid intake and breast cancer survival among women on Long Island."
},
{
"docid": "MED-2502",
"text": "Dietary restriction (DR) without malnutrition is widely regarded to be a universal mechanism for prolonging lifespan. It is generally believed that the benefits of DR arise from eating fewer calories (termed caloric restriction, CR). Here we argue that, rather than calories, the key determinant of the relationship between diet and longevity is the balance of protein to non-protein energy ingested. This ratio affects not only lifespan, but also total energy intake, metabolism, immunity and the likelihood of developing obesity and associated metabolic disorders. Among various possible mechanisms linking macronutrient balance to lifespan, the nexus between the TOR and AMPK signaling pathways is emerging as a central coordinator.",
"title": "Macronutrient balance and lifespan"
},
{
"docid": "MED-1227",
"text": "To correct methodologic flaws (Type II error, confounding variables, and nonblinding) in previous studies relating infant feeding to later obesity, we conducted case-control studies of 639 patients 12 to 18 years of age attending our Adolescent Clinic, and 533 similarly aged healthy children attending a Montreal high school. Each subject was classified as either obese, overweight, or nonobese based on measurements of height, weight, and triceps and subscapular skinfolds. Feeding history, family history, and demographic data were later ascertained \"blindly\" by telephone interview. Analysis of the raw data revealed a significantly elevated estimated relative risk of not breast-feeding and a significant trend for rates of breast-feeding among the three weight groups. The magnitude of the protective effect appeared to rise slightly with increased duration of breast-feeding. Delayed introduction of solid foods provided little if any additional benefit. Several demographic and clinical variables proved to be confounding, but the significant protective effect of breast-feeding persisted even after controlling for confounders. We conclude that breast-feeding does protect against later obesity and attribute the conflicting results of previous studies to insufficient attention to methodologic standards.",
"title": "Do breast-feeding and delayed introduction of solid foods protect against subsequent obesity?"
},
{
"docid": "MED-4163",
"text": "OBJECTIVE: The health benefits of vegetarian diets are well-recognized; however, long-term adherence to these diets may be associated with nutrient inadequacies, particularly vitamins B12 and D, calcium, iron, zinc, and protein. The dietary reference intakes (DRIs) expert panels recommended adjustments to the iron, zinc, and calcium DRIs for vegetarians to account for decreased bioavailability, but no adjustments were considered necessary for the protein DRI under the assumption that vegetarians consume about 50% of protein from animal (dairy/egg) sources. This study examined dietary protein sources in a convenience sample of 21 young adult vegetarian women who completed food logs on 4 consecutive days (3 weekdays and 1 weekend day). METHODS: The daily contribution percentages of protein consumed from cereals, legumes, nuts/seeds, fruits/vegetables, and dairy/egg were computed, and the protein digestibility corrected amino acid score of the daily diets was calculated. RESULTS: The calculated total dietary protein digestibility score for participants was 82 ± 1%, which differed significantly (P < 0.001) from the DRI reference score, 88%, and the 4-d average protein digestibility corrected amino acid score for the sample was 80 ± 2%, which also differed significantly (P < 0.001) from the DRI reference value, 100%. The analyses indicated that animal protein accounted for only 21% of dietary protein. CONCLUSION: This research suggests that the protein DRI for vegetarians consuming less than the expected amounts of animal protein (45% to 50% of total protein) may need to be adjusted from 0.8 to about 1.0 g/kg to account for decreased protein bioavailability. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "Protein dietary reference intakes may be inadequate for vegetarians if low amounts of animal protein are consumed."
},
{
"docid": "MED-2082",
"text": "BACKGROUND: Reliable and timely information on the leading causes of death in populations, and how these are changing, is a crucial input into health policy debates. In the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010), we aimed to estimate annual deaths for the world and 21 regions between 1980 and 2010 for 235 causes, with uncertainty intervals (UIs), separately by age and sex. METHODS: We attempted to identify all available data on causes of death for 187 countries from 1980 to 2010 from vital registration, verbal autopsy, mortality surveillance, censuses, surveys, hospitals, police records, and mortuaries. We assessed data quality for completeness, diagnostic accuracy, missing data, stochastic variations, and probable causes of death. We applied six different modelling strategies to estimate cause-specific mortality trends depending on the strength of the data. For 133 causes and three special aggregates we used the Cause of Death Ensemble model (CODEm) approach, which uses four families of statistical models testing a large set of different models using different permutations of covariates. Model ensembles were developed from these component models. We assessed model performance with rigorous out-of-sample testing of prediction error and the validity of 95% UIs. For 13 causes with low observed numbers of deaths, we developed negative binomial models with plausible covariates. For 27 causes for which death is rare, we modelled the higher level cause in the cause hierarchy of the GBD 2010 and then allocated deaths across component causes proportionately, estimated from all available data in the database. For selected causes (African trypanosomiasis, congenital syphilis, whooping cough, measles, typhoid and parathyroid, leishmaniasis, acute hepatitis E, and HIV/AIDS), we used natural history models based on information on incidence, prevalence, and case-fatality. We separately estimated cause fractions by aetiology for diarrhoea, lower respiratory infections, and meningitis, as well as disaggregations by subcause for chronic kidney disease, maternal disorders, cirrhosis, and liver cancer. For deaths due to collective violence and natural disasters, we used mortality shock regressions. For every cause, we estimated 95% UIs that captured both parameter estimation uncertainty and uncertainty due to model specification where CODEm was used. We constrained cause-specific fractions within every age-sex group to sum to total mortality based on draws from the uncertainty distributions. FINDINGS: In 2010, there were 52·8 million deaths globally. At the most aggregate level, communicable, maternal, neonatal, and nutritional causes were 24·9% of deaths worldwide in 2010, down from 15·9 million (34·1%) of 46·5 million in 1990. This decrease was largely due to decreases in mortality from diarrhoeal disease (from 2·5 to 1·4 million), lower respiratory infections (from 3·4 to 2·8 million), neonatal disorders (from 3·1 to 2·2 million), measles (from 0·63 to 0·13 million), and tetanus (from 0·27 to 0·06 million). Deaths from HIV/AIDS increased from 0·30 million in 1990 to 1·5 million in 2010, reaching a peak of 1·7 million in 2006. Malaria mortality also rose by an estimated 19·9% since 1990 to 1·17 million deaths in 2010. Tuberculosis killed 1·2 million people in 2010. Deaths from non-communicable diseases rose by just under 8 million between 1990 and 2010, accounting for two of every three deaths (34·5 million) worldwide by 2010. 8 million people died from cancer in 2010, 38% more than two decades ago; of these, 1·5 million (19%) were from trachea, bronchus, and lung cancer. Ischaemic heart disease and stroke collectively killed 12·9 million people in 2010, or one in four deaths worldwide, compared with one in five in 1990; 1·3 million deaths were due to diabetes, twice as many as in 1990. The fraction of global deaths due to injuries (5·1 million deaths) was marginally higher in 2010 (9·6%) compared with two decades earlier (8·8%). This was driven by a 46% rise in deaths worldwide due to road traffic accidents (1·3 million in 2010) and a rise in deaths from falls. Ischaemic heart disease, stroke, chronic obstructive pulmonary disease (COPD), lower respiratory infections, lung cancer, and HIV/AIDS were the leading causes of death in 2010. Ischaemic heart disease, lower respiratory infections, stroke, diarrhoeal disease, malaria, and HIV/AIDS were the leading causes of years of life lost due to premature mortality (YLLs) in 2010, similar to what was estimated for 1990, except for HIV/AIDS and preterm birth complications. YLLs from lower respiratory infections and diarrhoea decreased by 45-54% since 1990; ischaemic heart disease and stroke YLLs increased by 17-28%. Regional variations in leading causes of death were substantial. Communicable, maternal, neonatal, and nutritional causes still accounted for 76% of premature mortality in sub-Saharan Africa in 2010. Age standardised death rates from some key disorders rose (HIV/AIDS, Alzheimer's disease, diabetes mellitus, and chronic kidney disease in particular), but for most diseases, death rates fell in the past two decades; including major vascular diseases, COPD, most forms of cancer, liver cirrhosis, and maternal disorders. For other conditions, notably malaria, prostate cancer, and injuries, little change was noted. INTERPRETATION: Population growth, increased average age of the world's population, and largely decreasing age-specific, sex-specific, and cause-specific death rates combine to drive a broad shift from communicable, maternal, neonatal, and nutritional causes towards non-communicable diseases. Nevertheless, communicable, maternal, neonatal, and nutritional causes remain the dominant causes of YLLs in sub-Saharan Africa. Overlaid on this general pattern of the epidemiological transition, marked regional variation exists in many causes, such as interpersonal violence, suicide, liver cancer, diabetes, cirrhosis, Chagas disease, African trypanosomiasis, melanoma, and others. Regional heterogeneity highlights the importance of sound epidemiological assessments of the causes of death on a regular basis. FUNDING: Bill & Melinda Gates Foundation. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease S..."
},
{
"docid": "MED-5110",
"text": "Americans consume billions of hotdogs per year resulting in more than a billion dollars in retail sales. Package labels typically list some type of meat as the primary ingredient. The purpose of this study is to assess the meat and water content of several hotdog brands to determine if the package labels are accurate. Eight brands of hotdogs were evaluated for water content by weight. A variety of routine techniques in surgical pathology including routine light microscopy with hematoxylin-eosin-stained sections, special staining, immunohistochemistry, and electron microscopy were used to assess for meat content and for other recognizable components. Package labels indicated that the top-listed ingredient in all 8 brands was meat; the second listed ingredient was water (n = 6) and another type of meat (n = 2). Water comprised 44% to 69% (median, 57%) of the total weight. Meat content determined by microscopic cross-section analysis ranged from 2.9% to 21.2% (median, 5.7%). The cost per hotdog ($0.12-$0.42) roughly correlated with meat content. A variety of tissues were observed besides skeletal muscle including bone (n = 8), collagen (n = 8), blood vessels (n = 8), plant material (n = 8), peripheral nerve (n = 7), adipose (n = 5), cartilage (n = 4), and skin (n = 1). Glial fibrillary acidic protein immunostaining was not observed in any of the hotdogs. Lipid content on oil red O staining was graded as moderate in 3 hotdogs and marked in 5 hotdogs. Electron microscopy showed recognizable skeletal muscle with evidence of degenerative changes. In conclusion, hotdog ingredient labels are misleading; most brands are more than 50% water by weight. The amount of meat (skeletal muscle) in most brands comprised less than 10% of the cross-sectional surface area. More expensive brands generally had more meat. All hotdogs contained other tissue types (bone and cartilage) not related to skeletal muscle; brain tissue was not present.",
"title": "Applying morphologic techniques to evaluate hotdogs: what is in the hotdogs we eat?"
},
{
"docid": "MED-3139",
"text": "Background: Soy isoflavones have antiestrogenic and anticancer properties but also possess estrogen-like properties, which has raised concern about soy food consumption among breast cancer survivors. Objective: We prospectively evaluated the association between postdiagnosis soy food consumption and breast cancer outcomes among US and Chinese women by using data from the After Breast Cancer Pooling Project. Design: The analysis included 9514 breast cancer survivors with a diagnosis of invasive breast cancer between 1991 and 2006 from 2 US cohorts and 1 Chinese cohort. Soy isoflavone intake (mg/d) was measured with validated food-frequency questionnaires. HRs and 95% CIs were estimated by using delayed-entry Cox regression models, adjusted for sociodemographic, clinical, and lifestyle factors. Results: After a mean follow-up of 7.4 y, we identified 1171 total deaths (881 from breast cancer) and 1348 recurrences. Despite large differences in soy isoflavone intake by country, isoflavone consumption was inversely associated with recurrence among both US and Chinese women, regardless of whether data were analyzed separately by country or combined. No heterogeneity was observed. In the pooled analysis, consumption of ≥10 mg isoflavones/d was associated with a nonsignificant reduced risk of all-cause (HR: 0.87; 95% CI: 0.70, 1.10) and breast cancer–specific (HR: 0.83; 95% CI: 0.64, 1.07) mortality and a statistically significant reduced risk of recurrence (HR: 0.75; 95% CI: 0.61, 0.92). Conclusion: In this large study of combined data on US and Chinese women, postdiagnosis soy food consumption of ≥10 mg isoflavones/d was associated with a nonsignificant reduced risk of breast cancer–specific mortality and a statistically significant reduced risk of recurrence. One of the studies included in the After Breast Cancer Pooling Project, the Women's Healthy Eating & Living Study, was registered at clinicaltrials.gov as NCT00003787.",
"title": "Soy food intake after diagnosis of breast cancer and survival: an in-depth analysis of combined evidence from cohort studies of US and Chinese women"
},
{
"docid": "MED-4203",
"text": "Oxygen is vital for most organisms but, paradoxically, damages key biological sites. Oxygenic threat is met by antioxidants that evolved in parallel with our oxygenic atmosphere. Plants employ antioxidants to defend their structures against reactive oxygen species (ROS; oxidants) produced during photosynthesis. The human body is exposed to these same oxidants, and we have also evolved an effective antioxidant system. However, this is not infallible. ROS breach defences, oxidative damage ensues, accumulates with age, and causes a variety of pathological changes. Plant-based, antioxidant-rich foods traditionally formed the major part of the human diet, and plant-based dietary antioxidants are hypothesized to have an important role in maintaining human health. This hypothesis is logical in evolutionary terms, especially when we consider the relatively hypoxic environment in which humans may have evolved. In this paper, the human diet is discussed briefly in terms of its evolutionary development, different strategies of antioxidant defence are outlined, and evolution of dietary antioxidants is discussed from the perspectives of plant need and our current dietary requirements. Finally, possibilities in regard to dietary antioxidants, evolution, and human health are presented, and an evolutionary cost-benefit analysis is presented in relation to why we lost the ability to make ascorbic acid (vitamin C) although we retained an absolute requirement for it.",
"title": "Evolution of dietary antioxidants."
},
{
"docid": "MED-2352",
"text": "BACKGROUND: Carbohydrate-specific IgE antibodies present on nonprimate mammalian proteins were incriminated recently in delayed meat anaphylaxis. The aim of this study was to explore whether anaphylaxis to mammalian kidney is also associated with galactose-α-1,3-galactose (αGal)-specific IgE. METHODS: Fourteen patients with anaphylaxis to pork or beef kidney underwent prick tests to meat and kidney. Some patients also underwent skin tests to Erbitux(®) (cetuximab). IgE antibodies to αGal, swine urine proteins, beef and pork meat, serum albumin proteins, cat, and rFel d 1 were measured by ImmunoCAP(®). The αGal levels were estimated in meats and kidney by ELISA inhibition assay. Cross-reactivity between αGal and pork kidney was studied with the ImmunoCAP(®) inhibition assay. RESULTS: Among the 14 patients, 12 presented with anaphylactic shock. Reactions occurred within 2 h from exposure in 67% of patients. Associated risk factors were observed in 10 cases, and alcohol was the main cofactor. Three patients underwent an oral challenge to pork kidney, and anaphylaxis occurred after ingestion of small quantities (1-2 g). Prick tests to kidney were positive in 54% of patients. All tested patients showed positive skin tests to Erbitux(®). All patients tested positive for IgE to αGal, with levels ranging from 0.4 to 294 kU/l. IgE binding to αGal was inhibited by raw pork kidney extract (mean, 77%; range, 55-87%), which showed a high amount of αGal determinants. CONCLUSIONS: Pork or beef kidney anaphylaxis is related to αGal IgE. Its peculiar severity could be due to an elevated content of αGal epitopes in kidney. © 2012 John Wiley & Sons A/S.",
"title": "Anaphylaxis to pork kidney is related to IgE antibodies specific for galactose-alpha-1,3-galactose."
},
{
"docid": "MED-3129",
"text": "BRCA1 mutations have been associated with hereditary breast cancer only. Recent studies indicate that a subgroup of sporadic breast cancer might also be associated with reduction in BRCA1 mRNA levels and protein expression. However, the mechanism of reduced mRNA and protein expression is yet not fully elucidated. This study aims to assess BRCA1 protein expression and the role of BRCA1 promoter methylation in sporadic breast cancer in North Indian population and to correlate these with known prognostic factors and molecular profiles of breast cancer. BRCA1 protein expression was normal (>50 % tumour cells) in 41 (43 %) cases, reduced (20-50 % tumour cells) in 33 (35 %) cases and absent/markedly reduced (<20 % tumour cells) in 21 (22.1 %) cases. Cases which were negative for BRCA1 protein were more frequently positive for basal markers (29 versus 5 %) and were more often ER-negative (62 versus 39 %) than BRCA1-positive tumours. Methylation of BRCA1 promoter region was seen in 11/45 cases (24 %). All 11 cases showing BRCA1 methylation had absent (eight cases) or reduced (three cases) BRCA1 protein expression. BRCA1 protein-negative tumours were more frequently basal marker-positive and ER-negative, highlighting the 'BRCAness' of sporadic breast cancer with loss of BRCA1 protein expression through promoter hypermethylation similar to hereditary breast cancer with BRCA1 mutations. Loss of BRCA1 in sporadic breast cancer suggests that therapeutics targeting BRCA1 pathway in hereditary breast cancer like PARP inhibitors might be used as therapeutic targets for sporadic breast tumours.",
"title": "BRCA1-methylated sporadic breast cancers are BRCA-like in showing a basal phenotype and absence of ER expression."
},
{
"docid": "MED-2356",
"text": "Background In 2009, we reported a novel form of delayed anaphylaxis to red meat, which is related to serum IgE antibodies to the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal). Most of these patients had tolerated meat for many years previously. The implication is that some exposure in adult life had stimulated the production of these IgE antibodies. Objectives To investigate possible causes of this IgE antibody response, focusing on evidence related to tick bites, which are common in the region where these reactions occur. Methods Serum assays were carried out using biotinylated proteins and extracts bound to a streptavidin ImmunoCAP. Results Prospective studies on IgE antibodies in three subjects following tick bites showed an increase in IgE to alpha-gal of twenty-fold or greater. Other evidence included i) a strong correlation between histories of tick bites and IgE to alpha-gal (χ2=26.8, p<0.001), ii) evidence that these IgE antibodies are common in areas where the tick Amblyomma americanum is common, and iii) a significant correlation between IgE antibodies to alpha-gal and IgE antibodies to proteins derived from A. americanum (rs=0.75, p<0.001). Conclusion The results presented here provide evidence that tick bites are a cause, or possibly the only cause, of IgE specific for alpha-gal in this area of the United States. Both the number of subjects becoming sensitized and the titer of IgE antibodies to alpha-gal are striking. Here we report the first example of a response to an ectoparasite giving rise to an important form of food allergy.",
"title": "The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose"
},
{
"docid": "MED-4212",
"text": "Soya foods may protect against the development of breast cancer. Insulin-like growth factor (IGF)-1 is under investigation as a possible link between nutrition and cancer. We examined the effect of soya foods on circulating IGF-1 and IGF binding protein (BP)-3 levels among 196 healthy premenopausal women in a 2-year randomised nutritional trial. The intervention group consumed two daily servings of soya foods including tofu, soya milk, soya nuts and soya protein powder (equivalent to 50 mg isoflavones and 5-22 g soya protein per serving); the controls maintained their regular diet. Five serum samples at baseline, 3, 6, 12, and 24 months were collected in the morning during the luteal phase and analysed for IGF-1 and IGFBP-3 by double-antibody ELISA. We applied mixed models to investigate the intervention effect and predictors of serum levels while considering the repeated measurement design. Adherence with the study regimen was high and dropout rates were acceptable. Randomisation resulted in similar mean IGF-1 and IGFBP-3 levels by group. We did not observe a significant intervention effect on IGF-1, IGFBP-3, and their molar ratio during the entire study period. However, urinary isoflavone excretion during the study period was positively associated with IGF-1 (P=0.04) and the IGF-1:IGFBP-3 ratio (P=0.06). The effect was consistent over time. Adding soya foods to the diet of premenopausal women does not appear to lower serum levels of IGF-1 and IGFBP-3; if anything, the greater protein intake from soya may lead to a small increase in IGF-1 serum levels.",
"title": "Insulin-like growth factor-1 and binding protein-3 in a 2-year soya intervention among premenopausal women."
},
{
"docid": "MED-3245",
"text": "Cruciferous vegetables, tomato sauce, and legumes have been associated with reduced risk of incident advanced prostate cancer. In vitro and animal studies suggest these foods may inhibit progression of prostate cancer, but there are limited data in men. Therefore, we prospectively examined whether intake of total vegetables, and specifically cruciferous vegetables, tomato sauce, and legumes, after diagnosis reduce risk of prostate cancer progression among 1,560 men diagnosed with non-metastatic prostate cancer and participating in the Cancer of the Prostate Strategic Urologic Research Endeavor, a United States prostate cancer registry. As a secondary analysis, we also examined other vegetable sub-groups, total fruit, and subgroups of fruits. The participants were diagnosed primarily at community-based clinics and followed from 2004–2009. We assessed vegetable and fruit intake via a semi-quantitative food frequency questionnaire, and ascertained prostate cancer outcomes via urologist report and medical records. We observed 134 events of progression (53 biochemical recurrences, 71 secondary treatments likely due to recurrence, six bone metastases, four prostate cancer deaths) during 3,171 person-yrs. Men in the fourth quartile of post-diagnostic cruciferous vegetable intake had a statistically significant 59% decreased risk of prostate cancer progression compared to men in the lowest quartile (hazard ratio (HR): 0.41; 95% confidence interval (CI): 0.22, 0.76; p-trend: 0.003). No other vegetable or fruit group was statistically significantly associated with risk of prostate cancer progression. In conclusion, cruciferous vegetable intake after diagnosis may reduce risk of prostate cancer progression.",
"title": "Vegetable and fruit intake after diagnosis and risk of prostate cancer progression"
},
{
"docid": "MED-1723",
"text": "The lower rates of some cancers in Asian countries than in Western countries may be partly because of diet, although the mechanisms are unknown. The aim of this cross-sectional study was to determine whether a plant-based (vegan) diet is associated with a lower circulating level of insulin-like growth factor I (IGF-I) compared with a meat-eating or lacto-ovo-vegetarian diet among 292 British women, ages 20-70 years. The mean serum IGF-I concentration was 13% lower in 92 vegan women compared with 99 meat-eaters and 101 vegetarians (P = 0.0006). The mean concentrations of both serum IGF-binding protein (IGFBP)-1 and IGFBP-2 were 20-40% higher in vegan women compared with meat-eaters and vegetarians (P = 0.005 and P = 0.0008 for IGFBP-1 and IGFBP-2, respectively). There were no significant differences in IGFBP-3, C-peptide, or sex hormone-binding globulin concentrations between the diet groups. Intake of protein rich in essential amino acids was positively associated with serum IGF-I (Pearson partial correlation coefficient; r = 0.27; P < 0.0001) and explained most of the differences in IGF-I concentration between the diet groups. These data suggest that a plant-based diet is associated with lower circulating levels of total IGF-I and higher levels of IGFBP-1 and IGFBP-2.",
"title": "The associations of diet with serum insulin-like growth factor I and its main binding proteins in 292 women meat-eaters, vegetarians, and vegans."
},
{
"docid": "MED-4053",
"text": "Heterocyclic amines (HCAs), potent mutagens and a risk factor for human cancers, are produced in meats cooked at high temperature. The aim of this study was to determine the HCA content in cooked meat products (beef, chicken, pork, fish) prepared by various cooking methods (pan frying, oven broiling, and oven baking at 170 to 230°C) that are preferred by U.S. meat consumers. The primary HCAs in these samples were PhIP (2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine) (1.49-10.89ng/g), MeIQx (2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline) (not detected-4.0ng/g), and DiMeIQx (2-amino-3,4,8-trimethyl-imidazo [4,5-f]quinoxaline) (not detected-3.57ng/g). Type and content of HCAs in cooked meat samples were highly dependent on cooking conditions. The total HCA content in well-done meat was 3.5 times higher than that of medium-rare meat. Fried pork (13.91ng/g) had higher levels of total HCAs than fried beef (8.92ng/g) and fried chicken (7.00ng/g). Among the samples, fried bacon contained the highest total HCA content (17.59ng/g). Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Occurrence of heterocyclic amines in cooked meat products."
},
{
"docid": "MED-2450",
"text": "Background Atopy is not uncommon among children living in rural Crete, but wheeze and rhinitis are rare. A study was undertaken to examine whether this discrepancy could be attributed to a high consumption of fresh fruit and vegetables or adherence to a traditional Mediterranean diet. Methods A cross‐sectional survey was performed in 690 children aged 7–18 years in rural Crete. Parents completed a questionnaire on their child's respiratory and allergic symptoms and a 58‐item food frequency questionnaire. Adherence to a Mediterranean diet was measured using a scale with 12 dietary items. Children underwent skin prick tests with 10 common aeroallergens. Results 80% of children ate fresh fruit (and 68% vegetables) at least twice a day. The intake of grapes, oranges, apples, and fresh tomatoes—the main local products in Crete—had no association with atopy but was protective for wheezing and rhinitis. A high consumption of nuts was found to be inversely associated with wheezing (OR 0.46; 95% CI 0.20 to 0.98), whereas margarine increased the risk of both wheeze (OR 2.19; 95% CI 1.01 to 4.82) and allergic rhinitis (OR 2.10; 95% CI 1.31 to 3.37). A high level of adherence to the Mediterranean diet was protective for allergic rhinitis (OR 0.34; 95% CI 0.18 to 0.64) while a more modest protection was observed for wheezing and atopy. Conclusion The results of this study suggest a beneficial effect of commonly consumed fruits, vegetables and nuts, and of a high adherence to a traditional Mediterranean diet during childhood on symptoms of asthma and rhinitis. Diet may explain the relative lack of allergic symptoms in this population.",
"title": "Protective effect of fruits, vegetables and the Mediterranean diet on asthma and allergies among children in Crete"
},
{
"docid": "MED-2295",
"text": "BACKGROUND: Intake of dietary fiber has been recommended for many years as part of the guidelines from the American Heart Association, the Institute of Medicine, and other groups. The recommended Adequate Intake for dietary fiber for adults is 25 to 38 g/day (14 g/1,000 kcal/day). OBJECTIVE: To determine the average daily intake of dietary fiber among adults during the past decade and, specifically, to document progress toward national goals. DESIGN: Cross-sectional weighted data from the National Health and Nutrition Examination Survey among adults aged 18 years and older. PARTICIPANTS/SETTING: Data were collected from noninstitutionalized adults aged 18 years and older using a nationally representative, complex, multistage, probability-based survey of people living in the United States that was conducted by the National Center for Health Statistics. MAIN OUTCOME MEASURES: Daily dietary fiber intake by members of the US population based on 2-year groupings of the continuous survey from 1999 to 2008. RESULTS: Mean daily dietary fiber intake for 1999-2000 was 15.6 g/day, for 2001-2002 intake was 16.1g/day, for 2003-2004 intake was 15.5 g/day, for 2005-2006 intake was 15.8 g/day, and for 2007-2008 intake was 15.9 g/day. Participants with obesity (body mass index ≥30) consistently reported lower fiber intake than did individuals with normal weight or overweight (14.6 to 15.4 g/day and 15.6 to 16.8 g/day, respectively; P<0.0001). Mexican Americans had significantly higher intake in 1999-2000 than non-Hispanic whites (18.0 vs 16.1g/day; P<0.05), but Mexican Americans' intake did not increase over time (17.7 g/day in 2007-2008). Non-Hispanic blacks had fiber intake of 12.5 g/day at baseline that increased modestly to 13.1 g/day by 2007-2008. CONCLUSIONS: Daily fiber intake generally has not progressed toward national goals during the past decade, but there are some differences according to health and social factors. Additional clinical practice and public health strategies are needed. Copyright © 2012 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.",
"title": "Trends in dietary fiber intake in the United States, 1999-2008."
},
{
"docid": "MED-4305",
"text": "Influence of diet composition on mood during weight-reducing diets was studied in healthy young women of normal weight. A broad range of macronutrient intake was achieved by means of divergent dietary instructions for the composition of a 1,000 kcal per day diet adhered to for six weeks. Global mood during the last three weeks of the diet was significantly better in the \"vegetarian\" than in the \"mixed\" diet group. During this time a significant correlation was observed between relative carbohydrate intake and global mood (r = -0.74; p less than 0.01) and between the ratio of plasma tryptophan to other large neutral amino acids (a predictor of tryptophan flow into brain) and global mood (r = -0.52; p less than 0.05). Results suggest that group differences are related to differences in carbohydrate intake. It is hypothesized that impairment of central serotonergic function due to reduced tryptophan availability can prompt mood deterioration in situations of relatively low carbohydrate intake.",
"title": "Macronutrient intake, plasma large neutral amino acids and mood during weight-reducing diets."
},
{
"docid": "MED-2658",
"text": "The prevalence of allergic diseases has increased in recent decades. Allergic diseases, particularly asthma, are complex diseases with strong gene-environment interactions. Epidemiological studies have identified a variety of risk factors for the development of allergic diseases. Among them, endocrine-disrupting chemicals (EDCs) play an important role in triggering or exacerbating these diseases. 4-Nonylphenol (NP) and 4-octylphenol (OP)--two major alkylphenols--have been recognized as common toxic and xenobiotic endocrine disrupters. Due to their low solubility, high hydrophobicity, and low estrogenic activity, they tend to accumulate in the human body and may be associated with the adverse effects of allergic diseases. Recently, new evidence has supported the importance of alkylphenols in the in vitro allergic response. This review focuses on the effects of alkylphenols on several key cell types in the context of allergic inflammation. Copyright © 2012. Published by Elsevier B.V.",
"title": "Alkylphenols--potential modulators of the allergic response."
},
{
"docid": "MED-2511",
"text": "Residents of Okinawa, the southernmost prefecture of Japan, are known for their long average life expectancy, high numbers of centenarians, and accompanying low risk of age-associated diseases. Much of the longevity advantage in Okinawa is thought to be related to a healthy lifestyle, particularly the traditional diet, which is low in calories yet nutritionally dense, especially with regard to phytonutrients in the form of antioxidants and flavonoids. Research suggests that diets associated with a reduced risk of chronic diseases are similar to the traditional Okinawan diet, that is, vegetable and fruit heavy (therefore phytonutrient and antioxidant rich) but reduced in meat, refined grains, saturated fat, sugar, salt, and full-fat dairy products. Many of the characteristics of the diet in Okinawa are shared with other healthy dietary patterns, such as the traditional Mediterranean diet or the modern DASH (Dietary Approaches to Stop Hypertension) diet. Features such as the low levels of saturated fat, high antioxidant intake, and low glycemic load in these diets are likely contributing to a decreased risk for cardiovascular disease, some cancers, and other chronic diseases through multiple mechanisms, including reduced oxidative stress. A comparison of the nutrient profiles of the three dietary patterns shows that the traditional Okinawan diet is the lowest in fat intake, particularly in terms of saturated fat, and highest in carbohydrate intake, in keeping with the very high intake of antioxidant-rich yet calorie-poor orange-yellow root vegetables, such as sweet potatoes, and green leafy vegetables. Deeper analyses of the individual components of the Okinawan diet reveal that many of the traditional foods, herbs, or spices consumed on a regular basis could be labeled \"functional foods\" and, indeed, are currently being explored for their potential health-enhancing properties.",
"title": "The Okinawan diet: health implications of a low-calorie, nutrient-dense, antioxidant-rich dietary pattern low in glycemic load."
},
{
"docid": "MED-1714",
"text": "BACKGROUND: Western diets, obesity, and sedentary lifestyles are associated with increased cancer risk. The mechanisms responsible for this increased risk, however, are not clear. OBJECTIVE: We hypothesized that long-term low protein, low calorie intake and endurance exercise are associated with low concentrations of plasma growth factors and hormones that are linked to an increased risk of cancer. DESIGN: Plasma growth factors and hormones were evaluated in 21 sedentary subjects, who had been eating a low-protein, low-calorie diet for 4.4 +/- 2.8 y (x +/- SD age: 53.0 +/- 11 y); 21 endurance runners matched by body mass index (BMI; in kg/m2); and 21 age- and sex-matched sedentary subjects eating Western diets. RESULTS: BMI was lower in the low-protein, low-calorie diet (21.3 +/- 3.1) and runner (21.6 +/- 1.6) groups than in the Western diet (26.5 +/- 2.7; P < 0.005) group. Plasma concentrations of insulin, free sex hormones, leptin, and C-reactive protein were lower and sex hormone-binding globulin was higher in the low-protein, low-calorie diet and runner groups than in the sedentary Western diet group (all P < 0.05). Plasma insulin-like growth factor I (IGF-I) and the concentration ratio of IGF-I to IGF binding protein 3 were lower in the low-protein, low-calorie diet group (139 +/- 37 ng/mL and 0.033 +/- 0.01, respectively) than in the runner (177 +/- 37 ng/mL and 0.044 +/- 0.01, respectively) and sedentary Western (201 +/- 42 ng/mL and 0.046 +/- 0.01, respectively) diet groups (P < 0.005). CONCLUSIONS: Exercise training, decreased adiposity, and long-term consumption of a low-protein, low-calorie diet are associated with low plasma growth factors and hormones that are linked to an increased risk of cancer. Low protein intake may have additional protective effects because it is associated with a decrease in circulating IGF-I independent of body fat mass.",
"title": "Long-term low-protein, low-calorie diet and endurance exercise modulate metabolic factors associated with cancer risk."
},
{
"docid": "MED-3929",
"text": "Objective: To prospectively examine whether higher intakes of total flavonoids and their subclasses (flavanones, anthocyanins, flavan-3-ols, flavonols, flavones, and polymers) were associated with a lower risk of developing Parkinson disease (PD). Methods: In the current analysis, we included 49,281 men in the Health Professional Follow-up Study and 80,336 women from the Nurses' Health Study. Five major sources of flavonoid-rich foods (tea, berry fruits, apples, red wine, and orange/orange juice) were also examined. Flavonoid intake was assessed using an updated food composition database and a validated food frequency questionnaire. Results: We identified 805 participants (438 men and 367 women) who developed PD during 20–22 years of follow-up. In men, after adjusting for multiple confounders, participants in the highest quintile of total flavonoids had a 40%lower PD risk than those in the lowest quintile (hazard ratio [HR] = 0.60; 95% confidence interval 0.43, 0.83; p trend = 0.001). No significant relationship was observed in women (p trend = 0.62) or in pooled analyses (p trend = 0.23). In the pooled analyses for the subclasses, intakes of anthocyanins and a rich dietary source, berries, were significantly associated with a lower PD risk (HR comparing 2 extreme intake quintiles were 0.76 for anthocyanins and 0.77 for berries, respectively; p trend < 0.02 for both). Conclusions: Our findings suggest that intake of some flavonoids may reduce PD risk, particularly in men, but a protective effect of other constituents of plant foods cannot be excluded.",
"title": "Habitual intake of dietary flavonoids and risk of Parkinson disease"
},
{
"docid": "MED-2278",
"text": "OBJECTIVES: To investigate the anti-inflammatory and anti-oxidative effects of anthocyanins from cherries on Freund's adjuvant-induced arthritis (AIA) in rats. METHODS: Arthritis was induced intradermally by injection with 0.1 mL of complete Freund's adjuvant (CFA) into the right hind footpad of male Sprague Dawley (SD) rats. Anthocyanins at 40, 20 and 10 mg/kg (body weight) were administered orally to the treated rats for 28 days after the injection. Tumour necrosis factor-alpha (TNFalpha) in serum and prostaglandin E2 (PGE2) in paws were assayed by radioimmunoassay (RIA), and anti-oxidative effects was assayed by measuring total anti-oxidative capacity (T-AOC), superoxide dismutase (SOD) and malondialdehyde (MDA) in serum. RESULTS: Anthocyanins at 40 mg/kg significantly decreased the levels of TNFalpha in serum and PGE2 in paws, simultaneously improving the anti-oxidative status of AIA. We found that at this dosage T-AOC was potentized, the activity of SOD increased and the level of MDA in serum decreased. However, anthocyanins at 20 and 10 mg/kg had less effect on the inflammatory factors and anti-oxidative capacity of AIA. CONCLUSIONS: Anthocyanins have potential anti-inflammatory and anti-oxidative effects on AIA.",
"title": "Anti-inflammatory and anti-oxidative effects of cherries on Freund's adjuvant-induced arthritis in rats."
},
{
"docid": "MED-1616",
"text": "The role of very-low-carbohydrate ketogenic diets (VLCKD) in the long-term management of obesity is not well established. The present meta-analysis aimed to investigate whether individuals assigned to a VLCKD (i.e. a diet with no more than 50 g carbohydrates/d) achieve better long-term body weight and cardiovascular risk factor management when compared with individuals assigned to a conventional low-fat diet (LFD; i.e. a restricted-energy diet with less than 30% of energy from fat). Through August 2012, MEDLINE, CENTRAL, ScienceDirect,Scopus, LILACS, SciELO, ClinicalTrials.gov and grey literature databases were searched, using no date or language restrictions, for randomised controlled trials that assigned adults to a VLCKD or a LFD, with 12 months or more of follow-up. The primary outcome was bodyweight. The secondary outcomes were TAG, HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), systolic and diastolic blood pressure,glucose, insulin, HbA1c and C-reactive protein levels. A total of thirteen studies met the inclusion/exclusion criteria. In the overall analysis,five outcomes revealed significant results. Individuals assigned to a VLCKD showed decreased body weight (weighted mean difference 20·91 (95% CI 21·65, 20·17) kg, 1415 patients), TAG (weighted mean difference 20·18 (95% CI 20·27, 20·08) mmol/l, 1258 patients)and diastolic blood pressure (weighted mean difference 21·43 (95% CI 22·49, 20·37) mmHg, 1298 patients) while increased HDL-C(weighted mean difference 0·09 (95% CI 0·06, 0·12) mmol/l, 1257 patients) and LDL-C (weighted mean difference 0·12 (95% CI 0·04,0·2) mmol/l, 1255 patients). Individuals assigned to a VLCKD achieve a greater weight loss than those assigned to a LFD in the longterm; hence, a VLCKD may be an alternative tool against obesity.",
"title": "Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss: a meta-analysis of randomised controlled trials."
},
{
"docid": "MED-4556",
"text": "Tolerable upper intake levels (ULs) set by the Institute of Medicine (IOM) are important, in part because they are used for estimating the percentage of the population at potential risk of adverse effects from excessive nutrient intake. The IOM did not set ULs for trans fat, saturated fat, and cholesterol because any intake level above 0% of energy increased LDL cholesterol concentration and these three food components are unavoidable in ordinary diets. The purpose of the analysis presented in this review was to evaluate clinical trial and prospective observational data that were not previously considered for setting a UL with the aim of determining whether the current UL model could be used for saturated fat, trans fat, and cholesterol. The results of this analysis confirm the limitations of the risk assessment model for setting ULs because of its inability to identify a UL for food components, such as cholesterol, that lack an intake threshold associated with increased chronic disease risk. © 2011 International Life Sciences Institute.",
"title": "Tolerable upper intake levels for trans fat, saturated fat, and cholesterol."
},
{
"docid": "MED-2461",
"text": "This study aimed to evaluate the association of diet with respiratory symptoms and asthma in schoolchildren in Taipei, Taiwan. An in-class interview survey elicited experiences of asthma and respiratory symptoms and consumption frequencies of the major food categories in 2290 fifth graders. Respiratory symptoms surveyed included persistent cough, chest tightness, wheezing with cold, wheezing without cold, dyspnea-associated wheezing, and exercise-induced cough or wheezing. Results showed that the consumption of sweetened beverages had the strongest association with respiratory symptoms and was positively associated with six of the seven respiratory symptoms (all p < 0.05). The adjusted odds ratios (aOR) ranged from 1.05 (95% confidence interval (CI = 1.01-1.09) for exercise-induced cough to 1.09 (95% CI = 1.03-1.16) for wheezing without cold. Egg consumption was associated with 5 of the 7 respiratory symptoms. Consumptions of seafood, soy products, and fruits were each negatively associated with one of the seven respiratory symptoms (all p < 0.05). Consumption of seafood was negatively associated with physician-diagnosed asthma and consumptions of sweetened beverages and eggs were positively associated with suspected asthma (p < 0.05). In conclusion, the study suggests that diet is associated with the respiratory symptoms in schoolchildren in Taipei. Consumptions of sweetened beverages and eggs are associated with increased risk of respiratory symptoms and asthma whereas consumptions of soy products and fruits are associated with reduced risk of respiratory symptoms.",
"title": "The association of diet with respiratory symptoms and asthma in schoolchildren in Taipei, Taiwan."
},
{
"docid": "MED-2591",
"text": "Low-carbohydrate diets have become increasingly popular for weight loss. Although they may improve some metabolic markers, particularly in type 2 diabetes mellitus (T2D) or the metabolic syndrome (MS), their net effect on arterial wall function remains unclear. The objective was to evaluate the relation between dietary macronutrient composition and the small artery reactive hyperaemia index (saRHI), a marker of small artery endothelial function, in a cohort of patients at increased cardiovascular (CV) risk. The present cross-sectional study included 247 patients. Diet was evaluated by a 3-d food-intake register and reduced to a novel low-carbohydrate diet score (LCDS). Physical examination, demographic, biochemical and anthropometry parameters were recorded, and the saRHI was measured in each patient. Individuals in the lowest LCDS quartile (Q1, 45 % carbohydrate; 20 % protein; 32 % fat) had higher saRHI values than those in the top quartile (Q4, 29 % carbohydrate, 24 % protein, 40 % fat; 1.66 (sd 0.41) v. 1.52 (sd 0.22), P= 0.037). These results were particularly strong in patients with the MS (Q1 = 1.82 (sd 0.32) v. Q4 = 1.61 (sd 027); P= 0.021) and T2D (Q1 = 1.78 (sd 0.31) v. Q4 = 1.62 (sd 0.35); P= 0.011). Multivariate analysis demonstrated that individuals in the highest LCDS quartile had a significantly negative coefficient of saRHI, which was independent of confounders (OR -0.85; 95 % CI 0.19, 0.92; P= 0.031). These findings suggest that a dietary pattern characterised by a low amount of carbohydrate, but high amounts of protein and fat, is associated with a poorer small artery vascular reactivity in patients with increased CV risk.",
"title": "Negative effect of a low-carbohydrate, high-protein, high-fat diet on small peripheral artery reactivity in patients with increased cardiovascular ..."
},
{
"docid": "MED-1184",
"text": "It has been shown that feces of patients with ulcerative colitis uniformly contain sulfate reducing bacteria. Sulfide produced by these bacteria interferes with butyrate-dependent energy metabolism of cultured colonocytes and may be involved in the pathogenesis of ulcerative colitis. Mucosal biopsies from the sigmoid rectum of 10 patients (no caner, polyps, inflammatory bowel disease) were incubated with either NaCl, sodium hydrogen sulfide (1 mmol/L), a combination of both sodium hydrogen sulfide and butyrate (10 mmol/L), or butyrate. Mucosal proliferation was assessed by bromodeoxyuridine labeling of cells in S-phase. Compared to NaCl, sulfide increased the labeling of the entire crypt significantly, by 19% (p < 0.05). This effect was due to an expansion of the proliferative zone to the upper crypt (compartments 3-5), where the increase in proliferation was 54%. Sulfide-induced hyperproliferation was reversed when samples were coincubated with sulfide and butyrate. The study shows that sodium hydrogen sulfide induces mucosal hyperproliferation. Our data support a possible role of sulfide in the pathogenesis of UC and confirm the role of butyrate in the regulation of colonic proliferation and in the treatment of UC.",
"title": "Antagonistic effects of sulfide and butyrate on proliferation of colonic mucosa: a potential role for these agents in the pathogenesis of ulcerativ..."
},
{
"docid": "MED-4976",
"text": "Airborne cooking by-products from frying beef (hamburgers), pork (bacon strips) and soybean-based food (tempeh burgers) were collected, extracted, tested for mutagenicity and chemically analysed. The fumes generated by frying pork and beef were mutagenic, with 4900 and 1300 revertants/g of food cooked, respectively. No mutagenicity was detected in fumes from frying tempeh burgers. Bacon fried to a well-done but non-charred state was eight times more mutagenic in a microsuspension Ames/Salmonella test (TA98 with S-9) than hamburgers and about 350 times more mutagenic than tempeh burgers. Among food samples cooked to a well-done, non-charred state, bacon strips had almost 15-fold more mass (109.5 ng/g) than that of the beef, whereas no heterocyclic amine (HCA) was detected in the fried tempeh burgers. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was the most abundant HCA, followed by 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx). No 2-amino-9H-pyrido[2,3-b]indole (A alpha C) was detected in the food samples fried at about 200 degrees C, although it was present in the collected airborne products. The total amounts of HCAs in the smoke condensates were 3 ng/g from fried bacon, 0.37 ng/g from fried beef and 0.177 ng/g from fried soy-based food. This study indicates that cooks are potentially exposed to relatively high levels of airborne mutagens and carcinogens and that long-term sampling inside restaurants and kitchens may be warranted in order to assess the potential risk of prolonged exposure.",
"title": "Airborne mutagens produced by frying beef, pork and a soy-based food."
},
{
"docid": "MED-4216",
"text": "High levels of insulin-like growth factor 1 (IGF-1) are associated with increased risk of prostate cancer, whereas increased levels of some of its binding proteins (IGFBPs) seem to be protective. High intakes of dietary protein, especially animal and soy protein, appear to increase IGF-1. However, soy isoflavones have demonstrated anti-proliferative and apoptotic effects both in vitro and in vivo. We evaluated dietary intakes of total protein and soy isoflavones in relation to the IGF axis in prostate cancer patients making comprehensive lifestyle changes including a very low-fat vegan diet supplemented with soy protein (58 g/day). After one year, intervention group patients reported significantly higher intakes of dietary protein and soy isoflavones compared to usual-care controls (P < 0.001). IGF-1 increased significantly in both groups, whereas IGFBP-1 rose in the experimental group only (P < 0.01). Increases in vegetable protein over one year were associated with increases in IGFBP-1 among intervention group patients (P < 0.05). These results suggest that dietary protein and soy isoflavones, in the context of comprehensive lifestyle changes, may not significantly alter IGF-1. However, given the recent literature indicating that high intake of protein rich in essential amino acids (animal or soy protein) may increase IGF-1, it may be prudent for men with early stage prostate cancer not to exceed dietary protein recommendations.",
"title": "Relationship of dietary protein and soy isoflavones to serum IGF-1 and IGF binding proteins in the Prostate Cancer Lifestyle Trial."
},
{
"docid": "MED-4600",
"text": "Enough solid evidence now exists to offer women several fundamental strategies for healthy eating. They include emphasizing healthful unsaturated fats, whole grains, good protein “packages,” and fruits and vegetables; limiting consumption of trans and saturated fats, highly refined grains, and sugary beverages; and taking a multivitamin with folic acid and extra vitamin D as a nutritional safety net. A diet based on these principles is healthy through virtually all life stages, from young adulthood through planning for pregnancy, pregnancy, and on into old age.",
"title": "Essentials of Healthy Eating: A Guide"
},
{
"docid": "MED-3001",
"text": "Over the last three decades, the concept of Western disease has become well established. Medicine has approached this group of diseases by searching for new cures but has achieved relatively little success. We argue that medicine should now accept the failure of this strategy and place a major emphasis on prevention. The key objective is to change the climate of opinion so that prevention is taken seriously by the general population. The chief activity should be a wide ranging public education campaign so as to persuade people to live a healthier lifestyle. Medicine will require restructuring in order to carry out this work. Medical education needs to be reformed so that medical students receive the necessary training. This must be done as part of an integrated approach in which government, industry and medical research all play a major role. Governments should use taxation and subsidies in areas such as food and tobacco so as to shift consumption patterns towards healthier products. Governments must also tighten laws on tobacco sales and advertising, support health education, and improve food labelling. Industry must be made far more responsive to the health needs of the population. This should be done both by public education, so as to alter demand, and by government action. Medical research should change its emphasis from studying the detailed mechanisms of disease (\"complex research\") to studying the role of lifestyle factors (\"simple research\").",
"title": "Towards a new system of health: the challenge of Western disease."
},
{
"docid": "MED-2202",
"text": "The overall objective of this chapter is to review the past, present, and future role of the sweet potato (Ipomoea batatas [L.] Lam) in human nutrition. Specifically, the chapter describes the role of the sweet potato in human diets; outlines the biochemical and nutritional composition of the sweet potato with emphasis on its beta-carotene and anthocyanin contents; highlights sweet potato utilization, and its potential as value-added products in human food systems; and demonstrates the potential of the sweet potato in the African context. Early records have indicated that the sweet potato is a staple food source for many indigenous populations in Central and South Americas, Ryukyu Island, Africa, the Caribbean, the Maori people, Hawaiians, and Papua New Guineans. Protein contents of sweet potato leaves and roots range from 4.0% to 27.0% and 1.0% to 9.0%, respectively. The sweet potato could be considered as an excellent novel source of natural health-promoting compounds, such as beta-carotene and anthocyanins, for the functional food market. Also, the high concentration of anthocyanin and beta-carotene in sweet potato, combined with the high stability of the color extract make it a promising and healthier alternative to synthetic coloring agents in food systems. Starch and flour processing from sweet potato can create new economic and employment activities for farmers and rural households, and can add nutritional value to food systems. Repositioning sweet potato production and its potential for value-added products will contribute substantially to utilizing its benefits and many uses in human food systems. Multidisciplinary, integrated research and development activities aimed at improving production, storage, postharvest and processing technologies, and quality of the sweet potato and its potential value-added products are critical issues, which should be addressed globally.",
"title": "Sweet potato: a review of its past, present, and future role in human nutrition."
},
{
"docid": "MED-1612",
"text": "Type II diabetic subjects were given 50 g protein, 50 g glucose, or 50 g glucose with 50 g protein as a single meal in random sequence. The plasma glucose and insulin response was determined over the subsequent 5 h. The plasma glucose area above the baseline following a glucose meal was reduced 34% when protein was given with the glucose. When protein was given alone, the glucose concentration remained stable for 2 h and then declined. The insulin area following glucose was only modestly greater than with a protein meal (97 +/- 35, 83 +/- 19 microU X h/ml, respectively). When glucose was given with protein, the mean insulin area was considerably greater than when glucose or protein was given alone (247 +/- 33 microU X h/ml). When various amounts of protein were given with 50 g glucose, the insulin area response was essentially first order. Subsequently, subjects were given 50 g glucose or 50 g glucose with 50 g protein as two meals 4 h apart in random sequence. The insulin areas were not significantly different for each meal but were higher when protein + glucose was given. After the second glucose meal the plasma glucose area was 33% less than after the first meal. Following the second glucose + protein meal the plasma glucose area was markedly reduced, being only 7% as large as after the first meal. These data indicate that protein given with glucose will increase insulin secretion and reduce the plasma glucose rise in at least some type II diabetic persons.",
"title": "Effect of protein ingestion on the glucose and insulin response to a standardized oral glucose load."
},
{
"docid": "MED-2505",
"text": "BACKGROUND: Relative risk estimates suggest that effective implementation of behaviors commonly advocated in preventive medicine should increase life expectancy, although there is little direct evidence. OBJECTIVE: To test the hypothesis that choices regarding diet, exercise, and smoking influence life expectancy. METHODS: A total of 34 192 California Seventh-Day Adventists (75% of those eligible) were enrolled in a cohort and followed up from 1976 to 1988. A mailed questionnaire provided dietary and other exposure information at study baseline. Mortality for all subjects was ascertained by matching to state death tapes and the National Death Index. RESULTS: California Adventists have higher life expectancies at the age of 30 years than other white Californians by 7.28 years (95% confidence interval, 6.59-7.97 years) in men and by 4.42 years (95% confidence interval, 3.96-4.88 years) in women, giving them perhaps the highest life expectancy of any formally described population. Commonly observed combinations of diet, exercise, body mass index, past smoking habits, and hormone replacement therapy (in women) can account for differences of up to 10 years of life expectancy among Adventists. A comparison of life expectancy when these factors take high-risk compared with low-risk values shows independent effects that vary between 1.06 and 2.74 years for different variables. The effect of each variable is assessed with all others at either medium- or high-risk levels. CONCLUSIONS: Choices regarding diet, exercise, cigarette smoking, body weight, and hormone replacement therapy, in combination, appear to change life expectancy by many years. The longevity experience of Adventists probably demonstrates the beneficial effects of more optimal behaviors.",
"title": "Ten years of life: Is it a matter of choice?"
},
{
"docid": "MED-3305",
"text": "BACKGROUND AND AIM: The occurrence of malignant pleural mesothelioma (MPM) has been reported among population groups with no documented professional exposure to asbestos fibres living in different geographic areas. This paper reviews existing data related to non occupational MPM including its occurrence in the province of Catania (Sicily, Italy). METHODS: An electronic search of literature related to non occupational MPM was performed including the year 2005. RESULTS: Non occupational MPM in subjects living in areas contaminated by a variety of asbestos and non asbestos fibres has been well documented through a number of epidemiologic studies including cases series, case-control studies, and a cohort study. In addition, the observation of familial clustering of MPM, suggests that genetic factors may play a role in the pathogenesis of this malignancy. The epidemiological evidence also suggests that MPM may occur as a result of the interaction between environmental carcinogens, genetic factors, and virus infection. CONCLUSION: It is likely that genetic predisposition and non-occupational exposure to low doses of asbestos and asbestos-like fibres may concur to the development of malignant mesothelioma. However, additional epidemiological and laboratory studies are needed to further understand the relationship between environmental exposure and individual susceptibility to this malignancy.",
"title": "Non-occupational malignant pleural mesothelioma due to asbestos and non-asbestos fibres."
},
{
"docid": "MED-3454",
"text": "To determine if 6 weeks of supplementation with antioxidants could alleviate exercise-induced DNA damage, we studied 21 runners during a 50 km ultramarathon. Subjects were randomly assigned to one of two groups: (1) placebos (PL) or (2) antioxidants (AO) (1000 mg vitamin C and 400 IU RRR-alpha-tocopheryl acetate). The comet assay was used to assess DNA damage in circulating leukocytes at selected time points: pre-, mid-, and 2 h postrace and daily for 6 days postrace. All subjects completed the race: run time 7.1 +/- 0.1 h, energy expenditure 5008 +/- 80 kcal for women (n = 10) and 6932 +/- 206 kcal for men (n = 11). Overall, the percentage DNA damage increased at midrace (p <.02), but returned to baseline by 2 h postrace, indicating that the exercise bout induced nonpersistent DNA damage. There was a gender x treatment x time interaction (p <.01). One day postrace, women taking AO had 62% less DNA damage than women taking PL (p <.0008). In contrast, there were no statistically significant differences between the two treatment groups of men at any time point. Thus, endurance exercise resulted in DNA damage as shown by the comet assay and AO seemed to enhance recovery in women but not in men.",
"title": "Endurance exercise results in DNA damage as detected by the comet assay."
},
{
"docid": "MED-3783",
"text": "Fish odour syndrome (trimethylaminuria) is a metabolic syndrome caused by abnormal excretion of trimethylamine in the breath, urine, sweat, saliva and vaginal secretions. Trimethylamine is derived from the intestinal bacterial degradation of foods rich in choline and carnitine and is normally oxidised by the liver to odourless trimethylamine N-oxide which is then excreted in the urine. Impaired oxidation of trimethylamine is thought to be the cause of the fish odour syndrome and is responsible for the smell of rotting fish. Certain foods rich in choline exacerbate the condition and the patients have a variety of psychological problems. Recognition of the condition is important as dietary adjustments reduce the excretion of trimethylamine and may reduce the odour. Occasionally, a short course of metronidazole, neomycin and lactulose may suppress production of trimethylamine by reducing the activity of gut microflora. Keywords: fish odour syndrome; trimethylaminuria",
"title": "Fish odour syndrome"
},
{
"docid": "MED-4055",
"text": "Heterocyclic amines (HCAs) are formed when meat products such as beef, chicken, pork and fish are cooked at high temperatures. The most abundant HCA found in the human diet is 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP). PhIP causes mammary carcinomas in female rats and mice, and is associated with an increased risk of developing colon, breast, and prostate cancer in humans. PhIP is metabolized by cytochrome P-450s producing N-OH-PhIP. The N-OH-PhIP can be esterified by phase II enzymes forming an arylnitrenium ion that binds to DNA causing adducts. Furthermore, N-OH-PhIP may be reduced by cytochrome b5 reductase producing superoxide anions and hydroxyl radicals causing DNA strand breaks. Diallyl sulfide (DAS) has been shown to prevent cancer in several animal models, presumably by metabolic modulation. We hypothesize that PhIP produces reactive oxygen species causing DNA strand breaks and that DAS will inhibit the formation of PhIP induced DNA strand breaks. To test this hypothesis we treated normal breast epithelial (MCF-10A) cells with PhIP, DAS and a combination of PhIP and DAS. The detection of lipid peroxides was used as a surrogate for ROS. Lipid peroxides were detected using a PeroxiDetect kit (Sigma). PhIP increased the production of lipid peroxides and DAS decreased the PhIP-induced peroxidation by 47%. To determine if PhIP causes DNA strand breaks in MCF-10A cells, cells were treated for 3, 6, 9, and 24 h with PhIP (100 microM), DAS (100 microM) and a combination of PhIP (100 microM) and DAS (100 microM). DNA strand breaks were evaluated using the Comet assay. PhIP produced DNA strand breaks in a dose- and time-dependent fashion. We have shown that DAS inhibits PhIP-induced DNA strand breaks by inhibiting the production of reactive oxygen species. Therefore, we propose that DAS can prevent PhIP-induced breast cancer.",
"title": "Diallyl sulfide inhibits PhIP-induced DNA strand breaks in normal human breast epithelial cells."
},
{
"docid": "MED-5186",
"text": "We evaluated the role of dietary nutrients in the etiology of endometrial cancer in a population-based case-control study of 1,204 newly diagnosed endometrial cancer cases and 1,212 age frequency-matched controls. Information on usual dietary habits was collected during an in-person interview using a validated, quantitative food frequency questionnaire. Logistic regression analysis was conducted to evaluate the association of nutrients with endometrial cancer risk using an energy density method (e.g., nutrient intake/1,000 kilocalories of intake). Higher energy intake was associated with increased risk, which was attributable to animal source energy and a high proportion of energy from protein and fat. Odds ratios comparing highest versus lowest quintiles of intake were elevated for intake of animal protein (Odds ratio (OR) 5 2.0, 95% confidential interval: 1.5–2.7) and fat (OR 5 1.5, 1.2–2.0), but reduced for plant sources of these nutrients (OR 5 0.7, 0.5–0.9 for protein and OR 5 0.6, 0.5–0.8 for fat). Further analysis showed that saturated and monounsaturated fat intake was associated with elevated risk, while polyunsaturated fat intake was unrelated to risk. Dietary retinol, β-carotene, vitamin C, vitamin E, fiber, and vitamin supplements were inversely associated with risk. No significant association was observed for dietary vitamin B1 or vitamin B2. Our findings suggest that associations of dietary macronutrients with endometrial cancer risk may depend on their sources, with intake of animal origin nutrients being related to higher risk and intake of plant origin nutrients related to lower risk. Dietary fiber, retinol, β-carotene, vitamin C, vitamin E, and vitamin supplementation may decrease the risk of endometrial cancer.",
"title": "Nutritional factors in relation to endometrial cancer: A report from a population-based case-control study in Shanghai, China"
},
{
"docid": "MED-3193",
"text": "Background Multiple Myeloma (MM) is a B cell neoplasm causing lytic or osteopenic bone abnormalities. Whole body skeletal survey (WBSS), Magnetic resonance (MR) and 18F-FDG PET/CT are imaging techniques routinely used for the evaluation of bone involvement in MM patients. Aim As MM bone lesions may present low 18F-FDG uptake; the aim of this study was to assess the possible added value and limitations of 11C-Choline to that of 18F-FDG PET/CT in patients affected with MM. Methods Ten patients affected with MM underwent a standard 11C-Choline PET/CT and an 18F-FDG PET/CT within one week. The results of the two scans were compared in terms of number, sites and SUVmax of lesions. Results Four patients (40%) had a negative concordant 11C-Choline and 18F-FDG PET/CT scans. Two patients (20%) had a positive 11C-Choline and 18F-FDG PET/CT scans that identified the same number and sites of bone lesions. The remaining four patients (40%) had a positive 11C-Choline and 18F-FDG PET/CT scan, but the two exams identified different number of lesions. Choline showed a mean SUVmax of 5 while FDG showed a mean SUVmax of 3.8 (P = 0.042). Overall, 11C-Choline PET/CT scans detected 37 bone lesions and 18F-FDG PET/CT scans detected 22 bone lesions but the difference was not significant (P = 0.8). Conclusion According to these preliminary data, 11C-Choline PET/CT appears to be more sensitive than 18F-FDG PET/CT for the detection of bony myelomatous lesions. If these data are confirmed in larger series of patients, 11C-Choline may be considered a more appropriate functional imaging in association with MRI for MM bone staging.",
"title": "11C-choline vs. 18F-FDG PET/CT in assessing bone involvement in patients with multiple myeloma"
},
{
"docid": "MED-2519",
"text": "To date, the only intervention that has consistently been shown to slow the rate of aging, and to increase mean and maximum lifespan in short-lived species, is life-long calorie restriction. It is yet unclear whether long-term calorie restriction in longer lived species (i.e. primates and humans) will have a similar effect. In humans, several studies investigating short-term calorie restriction or \"weight loss\" programs suggest beneficial outcomes on parameters of cardiovascular disease. Studies on long-term calorie restriction are performed on a self-selected group of human subjects and show similar effects. However, few studies are currently investigating the quality of life and potential pitfalls of long-term calorie restriction in humans. It is likely that some of the physiological and psychological effects of caloric restriction that occur in animals may impact the human life very differently. For certain, calorie restriction has a plethora of health benefits in mammals, such as a reduction in age-related diseases such as cancer. However, despite the \"magic\" of CR, this intervention in humans may present itself with a number of health concerns, which may not be applicable to or impact the life of experimental animals, but may do so in humans. These potential pitfalls and \"side effects\" are not clearly addressed in the literature and will be a focus of this review.",
"title": "Caloric restriction in humans: potential pitfalls and health concerns."
},
{
"docid": "MED-2296",
"text": "This study aimed to investigate health belief as a major motive for diet and lifestyle behaviors of 100 vegans in the United States; and to determine congruence with selected health and nutrition outcomes. Response data from an administered questionnaire was analyzed. Statistical analyses determined the most common factors influencing diet choice; the number of vegans practicing particular lifestyle behaviors; body mass index; and prevalence of self-reported chronic disease diagnoses. Nutrient intakes were analyzed and assessed against Dietary Reference Intakes. Health was the most reported reason for diet choice (47%). In the health belief, animal welfare, and religious/other motive categories, low percentages of chronic disease diagnoses were reported: 27%, 11%, and 15%, respectively. There were no significant differences in health behaviors and indices among vegan motive categories, except for product fat content choices. Within the entire study population, health-related vegan motive coincided with regular exercise; 71% normal BMI (mean=22.6); minimal alcohol and smoking practices; frequently consumed vegetables, nuts, and grains; healthy choices in meal types, cooking methods, and low-fat product consumption; and adequate intakes for most protective nutrients when compared to reference values. But incongruence was found with 0% intake adequacy for vitamin D; and observation of excessive sodium use. Copyright © 2013 Elsevier Ltd. All rights reserved.",
"title": "Vegan lifestyle behaviors: an exploration of congruence with health-related beliefs and assessed health indices."
},
{
"docid": "MED-2659",
"text": "U.S. and European regulators and researchers disagree over risks of a common class of surfactants.",
"title": "European bans on surfactant trigger transatlantic debate."
},
{
"docid": "MED-3132",
"text": "Little is known about dietitians current practice in counselling clients about the use of legumes in a low fat, high fibre diet. An exploratory e-mail questionnaire was sent to members of Dietitians of Canada to assess: dietitian use and preferences for legumes, dietitian practice, opinions about clients attitudes and preferences, and resource needs. Counsellors (n=256) had high personal use of legumes (64% > or = 1 serving/week) and frequently recommended legumes in counselling. The legumes most preferred by respondents and their clients were: peanuts, kidney beans, split peas, chickpeas, and lentils. Respondents often recommended canned bean products (76%) and tofu (61%), but other legume grocery products were less often recommended. The most common client issues identified were: flatulence (87% agreed), lack of familiarity (85%), and knowledge of preparation (82%). Dietitians were not satisfied with current resources to support practice, especially those respondents providing primarily clinical counselling services. The most requested resources were: recipes (90%), pamphlets (82%), food demonstrations (75%) and Internet sites (63%). Client level research is now needed to confirm the importance of the issues identified and to develop and test strategies for legume promotion in counselling.",
"title": "Legume promotion in counselling: an e-mail survey of dietitians."
},
{
"docid": "MED-2453",
"text": "BACKGROUND: Fresh fruit consumption and vitamin C intake have been associated with improved lung function in adults. Whether this is due to enhancement of lung growth, to a reduction in lung function decline, or to protection against bronchospasm is unclear. METHODS: In a cross- sectional school based survey of 2650 children aged 8-11 from 10 towns in England and Wales the main outcome measure was forced expiratory volume in one second (FEV1) standardised for body size and sex. Exposure was assessed by a food frequency questionnaire to parents and by measurement of plasma levels of vitamin C in a subsample of 278 children. RESULTS: FEV1 was positively associated with frequency of fresh fruit consumption. After adjustment for possible confounding variables including social class and passive smoking, those who never ate any fresh fruit had an estimated FEV1 some 79 ml (4.3%) lower than those who ate these items more than once a day (95% CI 22 to 136 ml). The association between FEV1 and fruit consumption was stronger in subjects with wheeze than in non-wheezers (p = 0.020 for difference in trend), though wheeze itself was not related to fresh fruit consumption. Frequency of consumption of salads and of green vegetables were both associated with FEV1 but the relationships were weaker than for fresh fruit. Plasma vitamin C levels were unrelated to FEV1 (r = - 0.01, p = 0.92) or to wheeze and were only weakly related to fresh fruit consumption (r = 0.13, p = 0.055). CONCLUSIONS: Fresh fruit consumption appears to have a beneficial effect on lung function in children. Further work is needed to confirm whether the effect is restricted to subjects who wheeze and to identify the specific nutrient involved.",
"title": "Effect of fresh fruit consumption on lung function and wheeze in children"
},
{
"docid": "MED-2476",
"text": "An increase in asthma and atopic disease has been recorded in many countries where society has become more prosperous. We have investigated two possible explanations: a reduction in childhood infections and a change in diet. In a cohort of people followed up since 1964, originally selected as a random sample of primary school children, we have investigated the relevance of family size and the common childhood infectious diseases to development of eczema, hay fever and asthma. Although membership of a large family reduced risks of hay fever and eczema (but not asthma), this was not explained by the infections the child had suffered. Indeed, the more infections the child had had, the greater the likelihood of asthma, although measles gave a modest measure of protection. We have investigated dietary factors in two separate studies. In the first, we have shown the risks of bronchial hyper-reactivity are increased seven-fold among those with the lowest intake of vitamin C, while the lowest intake of saturated fats gave a 10-fold protection. In the second, we have shown that the risk of adult-onset wheezy illness is increased five-fold by the lowest intake of vitamin E and doubled by the lowest intake of vitamin C. These results were supported by direct measurements of the vitamins and triglycerides in plasma. We have proposed that changes in the diet of pregnant women may have reflected those observed in the population as a whole and that these may have resulted in the birth of cohorts of children predisposed to atopy and asthma. The direct test of this is to study the diet and nutritional status of a large cohort of pregnant women and to follow their offspring forward. This is our current research.",
"title": "Diet, infection and wheezy illness: lessons from adults."
},
{
"docid": "MED-2475",
"text": "Current understanding of the use of exclusion diets in the management of asthma in children is limited and controversial. The aim of this study was to examine the effects of excluding eggs and milk on the occurrence of symptoms in children with asthma and involved 22 children aged between three and 14 years clinically diagnosed as having mild to moderate disease. The investigation was single blind and prospective, and parents were given the option of volunteering to join the 'experiment' group, avoiding eggs, milk and their products for eight weeks, or the 'control' group, who consumed their customary food. Thirteen children were recruited to the experimental group and nine to the control group. A trained paediatrician at the beginning and end of the study period assessed the children. A seven-day assessment of food intake was made before, during and immediately after the period of dietary intervention in both groups. A blood sample was taken from each child for determination of food specific antibodies and in those children who could do so, the peak expiratory flow rate (PEFR) was measured. Based on the recommended nutrient intake (RNI), the mean percentage energy intake of the children in the experimental group was significantly lower (p < 0.05) in the experimental group. After the eight-week study period and compared with baseline values, the mean serum anti-ovalbumin IgG and anti-beta lactoglobulin IgG concentrations were statistically significantly reduced (p < 0.05) for both in the experimental group. In contrast, the values for anti-ovalbumin IgG in the control group were significantly increased and those for anti-beta lactoglobulin IgG were practically unchanged. The total IgE values were unchanged in both groups. Over the study period, the PEFR in those children in the experimental group able to perform the test was significantly increased, but no such change was noted in the children in the control group who could do the test. These results suggest that even over the short time period of eight weeks, an egg- and milk-free diet can reduce atopic symptoms and improve lung function in asthmatic children.",
"title": "The effects of exclusion of dietary egg and milk in the management of asthmatic children: a pilot study."
},
{
"docid": "MED-1716",
"text": "Obesity has reached epidemic proportions in the developed world. The progression from obesity to diabetes mellitus type 2, via metabolic syndrome, is recognised, and the significant associated increase in the risk of major human cancers acknowledged. We review the molecular basis of the involvement of morbidly high concentrations of endogenous or therapeutic insulin and of insulin-like growth factors in the progression from obesity to diabetes and finally to cancer. Epidemiological and biochemical studies establish the role of insulin and hyperinsulinaemia in cancer risk and progression. Insulin-like growth factors, IGF-1 and IGF-2, secreted by visceral or mammary adipose tissue have significant paracrine and endocrine effects. These effects can be exacerbated by increased steroid hormone production. Structural studies elucidate how each of the three ligands, insulin, IGF-1, and IGF-2, interacts differently with isoforms A and B of the insulin receptor and with type I IGF receptor and explain how these protagonists contribute to diabetes-associated cancer. The above should inform appropriate treatment of cancers that arise in obese individuals and in those with diabetes mellitus type 2. Novel drugs that target the insulin and insulin-like growth factor signal transduction pathways are in clinical trial and should be effective if appropriate biomarker-informed patient stratification is implemented.",
"title": "A Twenty-First Century Cancer Epidemic Caused by Obesity: The Involvement of Insulin, Diabetes, and Insulin-Like Growth Factors"
},
{
"docid": "MED-3216",
"text": "Increasing dietary protein results in an increase in urinary calcium. Despite over 80 y of research, the source of the additional urinary calcium remains unclear. Because most calcium balance studies found little effect of dietary protein on intestinal calcium absorption, it was assumed that the skeleton was the source of the calcium. The hypothesis was that the high endogenous acid load generated by a protein-rich diet would increase bone resorption and skeletal fracture. However, there are no definitive nutrition intervention studies that show a detrimental effect of a high protein diet on the skeleton and the hypothesis remains unproven. Recent studies from our laboratory demonstrate that dietary protein affects intestinal calcium absorption. We conducted a series of short-term nutrition intervention trials in healthy adults where dietary protein was adjusted to either low, medium or high. The highest protein diet resulted in hypercalciuria with no change in serum parathyroid hormone. Surprisingly, within 4 d, the low protein diet induced secondary hyperparathyroidism that persisted for 2 wk. The secondary hyperparathyroidism induced by the low protein diet was attributed to a reduction in intestinal calcium absorption (as assessed by dual stable calcium isotopes). The long-term consequences of these low protein-induced changes in calcium metabolism are not known, but they could be detrimental to skeletal health. Several recent epidemiological studies demonstrate reduced bone density and increased rates of bone loss in individuals habitually consuming low protein diets. Therefore, studies are needed to determine whether low protein intakes directly affect rates of bone resorption, bone formation or both.",
"title": "Low protein intake: the impact on calcium and bone homeostasis in humans."
},
{
"docid": "MED-3236",
"text": "A first objective of the present study was to estimate the acid-base balance of the food intake in vegetarians and non-vegetarians. A second objective was to evaluate if additional input of specific food items on the existing potential renal acid load (PRAL) list was necessary for the comparison of the two dietary patterns. Thirty vegetarians between the age of 18 and 30 years were matched for sex, age and BMI with 30 non-vegetarians. Based on the 3-days food diaries the acid-base status of the food intake was estimated using the PRAL method. Mean PRAL values as estimated with the standard table yielded an alkaline load of -5.4 +/- 14.4 mEq/d in the vegetarians compared to an acid load of 10.3 +/- 14.4 mEq/d in the nonvegetarians (p<0.001). Mean PRAL values as estimated with the extended table yielded an alkaline load of -10.9 +/-19.7 mEq/d in the vegetarians compared to an acid load of 13.8 +/- 17.1 mEq/d for the non-vegetarians (p<0.001). The findings of this study indicate that vegetarian food intake produces more alkaline outcomes compared to non-vegetarian diets. The use of the standard PRAL table was sufficient for discrimination between the two diets.",
"title": "Nutrient based estimation of acid-base balance in vegetarians and non-vegetarians."
},
{
"docid": "MED-3315",
"text": "PURPOSE: To test the hypothesis that exposure to poultry oncogenic viruses that widely occurs occupationally in poultry workers and in the general population, may be associated with increased risks of deaths from liver and pancreatic cancers, and to identify new risk factors. METHODS: A pilot case-cohort study of both cancers within a combined cohort of 30,411 highly exposed poultry workers and 16,408 control subjects was conducted, and risk assessed by logistic regression odds ratios (OR) and proportional hazards risk ratios. RESULTS: New occupational findings were recorded respectively for pancreatic/liver cancers, for slaughtering of poultry (OR = 8.9, 95% confidence interval [CI]: 2.7-29.3)/OR = 9.1, 95% CI: 1.9-42.9); catching of live chickens (OR = 3.6, 95% CI: 1.2-10.9)/OR = 1.0, 95% CI: 0.1-8.5); killing other types of animals for food (OR = 4.8, 95% CI: 1.5-16.6)/OR = 2.0, 95% CI: 0.2-18.2), and ever worked on a pig raising farm (OR = 3.0, 95% CI: 1.0-8.2) for pancreatic cancer only. New non-occupational findings for liver cancer were for receiving immunization with yellow fever vaccine (OR = 8.7, 95% CI: 1.0-76.3); and vaccination with typhoid vaccine (OR = 6.3, 95% CI: 1.1-37.4). The study also confirmed previously reported risk factors for both diseases. CONCLUSIONS: This study provides preliminary evidence that exposure to poultry oncogenic viruses may possibly be associated with the occurrence of liver and pancreatic cancers. Case-control studies nested within occupational cohorts of highly exposed subjects of sufficient statistical power may provide an efficient and valid method of investigating/confirming these findings. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "A pilot case-cohort study of liver and pancreatic cancers in poultry workers."
},
{
"docid": "MED-3358",
"text": "BACKGROUND & AIMS: Taste sensitivity to fatty acids influences food ingestion and may regulate fat intake and body weight status. Fatty acids are detected via homologous receptors within the mouth and gastrointestinal (GI) tract, where attenuated sensitivity may be associated with greater fat intake and BMI. This study aimed to extend observations surrounding fatty acid taste, specifically the types of foods consumed and dietary behaviours that may be associated with fatty acid taste sensitivity. METHODS: 51 subjects (41 female; BMI, 21.4 ± 0.46 kg/m², age, 20 ± 0.52 yrs, 10 male; BMI, 23.6 ± 1.4 kg/m², age, 22 ± 1 yrs) were screened for oral sensitivity to oleic acid (3.8 mM) using triplicate sensory evaluations, and classified as hypersensitive; (3/3 correct identifications), or hyposensitive, (<3/3). Fat-taste perception (using sensory-matched custards made with 0, 2, 6, 10% oil), recent diet (4-day diet record) and food habits and behaviours (food habits and behaviours questionnaire) were also established. RESULTS: 75% (n = 38) of subjects were classified as hyposensitive to oleic acid and these subjects differed from those who were classified as hypersensitive. Hyposensitive subjects consumed significantly more energy, fat, saturated fat, fatty foods (butter, meat, dairy), had greater BMI and were less perceptive of small changes in the fat content of custard (all P < 0.05), compared to hypersensitive subjects. CONCLUSION: An inability to perceive low concentrations of fatty acids in foods was associated with greater consumption of fatty foods, specifically butter, meat, dairy, and increasing BMI. 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.",
"title": "Oral sensitivity to oleic acid is associated with fat intake and body mass index."
},
{
"docid": "MED-3780",
"text": "Metabolomics studies hold promise for discovery of pathways linked to disease processes. Cardiovascular disease (CVD) represents the leading cause of death and morbidity worldwide. A metabolomics approach was used to generate unbiased small molecule metabolic profiles in plasma that predict risk for CVD. Three metabolites of the dietary lipid phosphatidylcholine, namely choline, trimethylamine N-oxide (TMAO), and betaine, were identified and then shown to predict risk for CVD in an independent large clinical cohort. Dietary supplementation of mice with choline, TMAO or betaine promoted up-regulation of multiple macrophage scavenger receptors linked to atherosclerosis, and supplementation with choline or TMAO promoted atherosclerosis. Studies using germ-free mice confirmed a critical role for dietary choline and gut flora in TMAO production, augmented macrophage cholesterol accumulation and foam cell formation. Suppression of intestinal microflora in atherosclerosis-prone mice inhibited dietary choline-enhanced atherosclerosis. Genetic variations controlling expression of flavin monooxygenases (FMOs), an enzymatic source of TMAO, segregated with atherosclerosis in hyperlipidemic mice. Discovery of a relationship between gut flora-dependent metabolism of dietary phosphatidylcholine and CVD pathogenesis provides opportunities for development of both novel diagnostic tests and therapeutic approaches for atherosclerotic heart disease.",
"title": "Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease"
},
{
"docid": "MED-3227",
"text": "Although high-protein diets induce hypercalciuria in humans, the source of the additional urinary calcium remains unclear. One hypothesis is that the high endogenous acid load of a high-protein diet is partially buffered by bone, leading to increased skeletal resorption and hypercalciuria. We used dual stable calcium isotopes to quantify the effect of a high-protein diet on calcium kinetics in women. The study consisted of 2 wk of a lead-in, well-balanced diet followed by 10 d of an experimental diet containing either moderate (1.0 g/kg) or high (2.1 g/kg) protein. Thirteen healthy women received both levels of protein in random order. Intestinal calcium absorption increased during the high-protein diet in comparison with the moderate (26.2 +/- 1.9% vs. 18.5 +/- 1.6%, P < 0.0001, mean +/- sem) as did urinary calcium (5.23 +/- 0.37 vs. 3.57 +/- 0.35 mmol/d, P < 0.0001, mean +/- sem). The high-protein diet caused a significant reduction in the fraction of urinary calcium of bone origin and a nonsignificant trend toward a reduction in the rate of bone turnover. There were no protein-induced effects on net bone balance. These data directly demonstrate that, at least in the short term, high-protein diets are not detrimental to bone.",
"title": "The impact of dietary protein on calcium absorption and kinetic measures of bone turnover in women."
},
{
"docid": "MED-3352",
"text": "The popularity of low- and reduced-fat foods has increased as consumers seek to decrease their energy consumption. Fat replacers may be used in fat-reduced products to maintain their sensory properties. However, these ingredients have been largely formulated to replicate nongustatory properties of fats to foods and have only achieved moderate success. There is increasing evidence that fats also activate the taste system and uniquely evoke responses that may influence product acceptance. Work supporting a taste component of fat has prompted questions about whether fat constitutes an additional \"primary\" or \"basic\" taste quality. This review briefly summarizes this evidence, focusing on human studies, when possible. Effective stimuli, possible receptors, and physiological changes due to oral fat exposure are discussed. Some studies suggest that there are fatty acid tasters and nontasters and if verified could have implications for targeted product development. © 2011 Institute of Food Technologists®",
"title": "Are free fatty acids effective taste stimuli in humans? Presented at the symposium \"The Taste for Fat: New Discoveries on the Role of Fat in Sensor..."
},
{
"docid": "MED-3138",
"text": "Background Many consumers avoid eating beans because they believe legume consumption will cause excessive intestinal gas or flatulence. An increasing body of research and the 2010 Dietary Guidelines for Americans supports the benefits of a plant-based diet, and legumes specifically, in the reduction of chronic disease risks. The purpose of the current research was to investigate the perception of increased flatulence and gastrointestinal discomfort among participants who consumed a ½ cup of beans daily for 8 or 12 weeks. Methods Participants in three studies to test the effects of beans on heart disease biomarkers completed the same weekly questionnaire to assess gastrointestinal discomfort issues such as increased flatulence, stool changes, and bloating. Studies 1 and 2 were randomized crossover trials. Participants consumed ½ cup of pinto beans, black-eyed peas, and canned carrots as control (n = 17) in Study 1 for three randomized 8-week phases. For Study 2, participants ate ½ cup baked beans or canned carrots as control (n = 29) for two randomized 8-week phases. Study 3 was a parallel arm trial with 40 subjects receiving ½ cup pinto beans and 40 consuming a control soup for 12 weeks. Changes in the frequency of perceived flatulence, stool characteristics, and bloating were the primary outcome measures. Chi-square distributions were examined for the presence or absence of symptoms and demographic characteristics to determine differences by gender, age, body mass index (BMI), and bean type. Results Less than 50% reported increased flatulence from eating pinto or baked beans during the first week of each trial, but only 19% had a flatulence increase with black-eyed peas. A small percentage (3-11%) reported increased flatulence across the three studies even on control diets without flatulence-producing components. Conclusions People's concerns about excessive flatulence from eating beans may be exaggerated. Public health nutritionists should address the potential for gastrointestinal discomfort when increasing fiber intake from beans with clients. It is important to recognize there is individual variation in response to different bean types.",
"title": "Perceptions of flatulence from bean consumption among adults in 3 feeding studies"
},
{
"docid": "MED-3140",
"text": "To identify protective dietary predictors amongst long-lived elderly people (N= 785), the \"Food Habits in Later Life \"(FHILL) study was undertaken among five cohorts in Japan, Sweden, Greece and Australia. Between 1988 and 1991, baseline data on food intakes were collected. There were 785 participants aged 70 and over that were followed up to seven years. Based on an alternative Cox Proportional Hazard model adjusted to age at enrollment (in 5-year intervals), gender and smoking, the legume food group showed 7-8% reduction in mortality hazard ratio for every 20g increase in daily intake with or without controlling for ethnicity (RR 0.92; 95% CI 0.85-0.99 and RR 0.93; 95% CI 0.87-0.99, respectively). Other food groups were not found to be consistently significant in predicting survival amongst the FHILL cohorts.",
"title": "Legumes: the most important dietary predictor of survival in older people of different ethnicities."
},
{
"docid": "MED-2200",
"text": "Cancer of the gallbladder is rare but fatal, and has an unusual geographic and demographic distribution. Gallstones and obesity have been suggested as possible risk factors. As diet is known to influence both these factors, we carried out the present study to evaluate the possible role of diet in gallbladder carcinogenesis. A case-control study involving 64 newly diagnosed cases of gallbladder cancer and 101 cases of gallstones was carried out. The dietary evaluation was carried out by the dietary recall method based on a preset questionnaire developed specifically for the present study, keeping in mind the common dietary habits prevailing in this part of the world. Odds ratios (OR) and 95% confidence interval (CI) were calculated for various dietary items. A significant reduction in odds ratio was seen with the consumption of radish (OR 0.4; 95% CI 0.17-0.94), green chilli (OR 0.45; 95% CI 0.21-0.94) and sweet potato (OR 0.33; 95% CI 0.13-0.83) among vegetables, and mango (OR 0.4; 95% CI 0.16-0.99), orange (OR; 0.45; 95% CI 0.22-0.93), melon (OR 0.3; 95% CI 0.14-0.64) and papaya (OR 0.44; 95% 0.2-0.64) among fruits. A reduction in odds was also seen with the consumption of cruciferous vegetables, beans, onion and turnip, however the difference was not statistically significant. On the other hand, an increase in the odds was observed with consumption of capsicum (OR 2.2), beef (OR 2.58), tea (OR 1.98), red chilli (OR 1.29) and mutton (OR 1.2), however the difference was statistically not significant. In conclusion, the results of the present study show a protective effect of vegetables and fruits on gallbladder carcinogenesis, but red meat (beef and mutton) was found to be associated with increased risk of gallbladder cancer.",
"title": "Diet and gallbladder cancer: a case-control study."
},
{
"docid": "MED-2367",
"text": "Naturally developing xenospecific Abs are well-documented barriers to xenograft transplantation in humans, but whether analogous xenoreactive T cell immunity develops is not known. We used an enzyme-linked immunospot assay to determine the frequency and cytokine profiles of xenoreactive PBLs from a panel of human volunteers. Because naive T cells produce only IL-2 in short term culture, IFN-gamma production by this approach is a measure of a memory immune response. Stimulation of human PBLs or purified T lymphocytes with stimulator cells from inbred swine revealed a high frequency of IFN-gamma producers with 5-fold fewer IL-2 producers. In contrast, lymphocytes obtained from neonatal umbilical cord blood contained swine-specific IL-2 producers but few IFN-gamma producers, which is what one would expect to find with a naive phenotype. Moreover, PBLs from adults with a history of abstention from pork consumption responded to swine cells with a significantly lower frequency of IFN-gamma producers than PBLs from adults with unrestricted diets did, suggesting that pork consumption may result in priming of swine-specific T cell immunity. Our findings provide the first evidence for naturally occurring xenospecific T cell immunity in humans. The detected strength of this memory response suggests that it will present a formidable barrier to transplantation of swine organs.",
"title": "Naturally developing memory T cell xenoreactivity to swine antigens in human peripheral blood lymphocytes."
},
{
"docid": "MED-4299",
"text": "The evolution of the human diet over the past 10,000 years from a Paleolithic diet to our current modern pattern of intake has resulted in profound changes in feeding behavior. Shifts have occurred from diets high in fruits, vegetables, lean meats, and seafood to processed foods high in sodium and hydrogenated fats and low in fiber. These dietary changes have adversely affected dietary parameters known to be related to health, resulting in an increase in obesity and chronic disease, including cardiovascular disease (CVD), diabetes, and cancer. Some intervention trials using Paleolithic dietary patterns have shown promising results with favorable changes in CVD and diabetes risk factors. However, such benefits may be offset by disadvantages of the Paleolithic diet, which is low in vitamin D and calcium and high in fish potentially containing environmental toxins. More advantageous would be promotion of foods and food ingredients from our ancestral era that have been shown to possess health benefits in the form of functional foods. Many studies have investigated the health benefits of various functional food ingredients, including omega-3 fatty acids, polyphenols, fiber, and plant sterols. These bioactive compounds may help to prevent and reduce incidence of chronic diseases, which in turn could lead to health cost savings ranging from $2 to $3 billion per year as estimated by case studies using omega-3 and plant sterols as examples. Thus, public health benefits should result from promotion of the positive components of Paleolithic diets as functional foods.",
"title": "Evolution of the human diet: linking our ancestral diet to modern functional foods as a means of chronic disease prevention."
},
{
"docid": "MED-2451",
"text": "BACKGROUND—A prospective cohort study of 2512 Welshmen aged 45-59 living in Caerphilly in 1979-1983 was used to investigate associations between diet and lung function. METHODS—At baseline (phase I) and at five year follow up (phase II), forced expiratory volume in one second (FEV1) was measured using a McDermott spirometer and dietary data were obtained using a semi-quantitative food frequency questionnaire. RESULTS—Good lung function, indicated by high maximum FEV1 given age and height, was associated with high intakes of vitamin C, vitamin E, β-carotene, citrus fruit, apples, and the frequent consumption of fruit juices/squashes. Lung function was inversely associated with magnesium intake but there was no evidence of an association with fatty fish. Following adjustment for confounders including body mass index, smoking history, social class, exercise, and total energy intake, only the associations with vitamin E and apples persisted, with lung function estimated to be 39 ml (95% confidence interval (CI) 9 to 69) higher for vitamin E intakes one standard deviation (SD) apart and 138 ml higher (95% CI 58to 218) for those eating five or more apples per week compared with non-consumers. Decline in lung function between phases was not significantly associated with the changing intakes of apples or vitamin E. An association between high average apple consumption and slow decline in lung function lost significance after adjustment for confounders. CONCLUSIONS—A strong positive association is seen between lung function and the number of apples eaten per week cross sectionally, consistent with a protective effect of hard fruit rather than soft/citrus fruit. The recent suggestion that such effects are reversible was not supported by our longitudinal analysis.",
"title": "Diet, lung function, and lung function decline in a cohort of 2512 middle aged men"
},
{
"docid": "MED-3320",
"text": "OBJECTIVES: Reticuloendotheliosis viruses (REV) are a group of retroviruses like avian leukosis/sarcoma viruses (ALSV) that naturally infect and cause cancers in chickens. We recently found that ALSV antibody levels were associated with job tasks in the poultry industry. The objectives of this study are to examine whether a similar association can be found with REV antibody levels and to examine the correlation between REV and ALSV antibody levels. METHODS: Relative risk was estimated comparing REV antibody levels of 45 poultry workers with those of 44 controls. The expected mean antibody level was predicted for the association with employment by a generalized linear model. Correlation coefficient was measured between ALSV and REV antibody levels. RESULTS: REV antibody levels were significantly higher in poultry workers than in control subjects and were associated with gender and employment conditions, especially employment duration. The relative risk was significantly higher for some job categories. A significant correlation was observed between REV and ALSV antibody levels, which was strong among poultry workers, but weak among the control subjects. CONCLUSION: Antibody levels can be validly used to identify certain job tasks associated with high risk of exposure to REV in the workplace, and the practical implication is recommendations for protection at these job tasks. Importantly, in situations where there is exposure to multiple pathogens in the workplace, the analysis of antibody levels of one pathogen may sufficiently represent exposure to the other correlated pathogens. This suggested exposure assessment may hold true for pathogens with a similar route of transmission.",
"title": "Industrial hygiene assessment of reticuloendotheliosis viruses exposure in the poultry industry."
},
{
"docid": "MED-4515",
"text": "BACKGROUND: Low-carbohydrate, high-animal protein diets, which are advocated for weight loss, may not promote the desired reduction in low-density lipoprotein cholesterol (LDL-C) concentration. The effect of exchanging the animal proteins and fats for those of vegetable origin has not been tested. Our objective was to determine the effect on weight loss and LDL-C concentration of a low-carbohydrate diet high in vegetable proteins from gluten, soy, nuts, fruits, vegetables, cereals, and vegetable oils compared with a high-carbohydrate diet based on low-fat dairy and whole grain products. METHODS: A total of 47 overweight hyperlipidemic men and women consumed either (1) a low-carbohydrate (26% of total calories), high-vegetable protein (31% from gluten, soy, nuts, fruit, vegetables, and cereals), and vegetable oil (43%) plant-based diet or (2) a high-carbohydrate lacto-ovo vegetarian diet (58% carbohydrate, 16% protein, and 25% fat) for 4 weeks each in a parallel study design. The study food was provided at 60% of calorie requirements. RESULTS: Of the 47 subjects, 44 (94%) (test, n = 22 [92%]; control, n = 22 [96%]) completed the study. Weight loss was similar for both diets (approximately 4.0 kg). However, reductions in LDL-C concentration and total cholesterol-HDL-C and apolipoprotein B-apolipoprotein AI ratios were greater for the low-carbohydrate compared with the high-carbohydrate diet (-8.1% [P = .002], -8.7% [P = .004], and -9.6% [P = .001], respectively). Reductions in systolic and diastolic blood pressure were also seen (-1.9% [P = .052] and -2.4% [P = .02], respectively). CONCLUSION: A low-carbohydrate plant-based diet has lipid-lowering advantages over a high-carbohydrate, low-fat weight-loss diet in improving heart disease risk factors not seen with conventional low-fat diets with animal products.",
"title": "The effect of a plant-based low-carbohydrate (\"Eco-Atkins\") diet on body weight and blood lipid concentrations in hyperlipidemic subjects."
},
{
"docid": "MED-3456",
"text": "Pharmacological antioxidant vitamins have previously been investigated for a prophylactic effect against exercise-induced oxidative stress. However, large doses are often required and may lead to a state of pro-oxidation and oxidative damage. Watercress contains an array of nutritional compounds such as β-carotene and α-tocopherol which may increase protection against exercise-induced oxidative stress. The present randomised controlled investigation was designed to test the hypothesis that acute (consumption 2 h before exercise) and chronic (8 weeks consumption) watercress supplementation can attenuate exercise-induced oxidative stress. A total of ten apparently healthy male subjects (age 23 (SD 4) years, stature 179 (SD 10) cm and body mass 74 (SD 15) kg) were recruited to complete the 8-week chronic watercress intervention period (and then 8 weeks of control, with no ingestion) of the experiment before crossing over in order to compete the single-dose acute phase (with control, no ingestion). Blood samples were taken at baseline (pre-supplementation), at rest (pre-exercise) and following exercise. Each subject completed an incremental exercise test to volitional exhaustion following chronic and acute watercress supplementation or control. The main findings show an exercise-induced increase in DNA damage and lipid peroxidation over both acute and chronic control supplementation phases (P< 0.05 v. supplementation), while acute and chronic watercress attenuated DNA damage and lipid peroxidation and decreased H₂O₂ accumulation following exhaustive exercise (P< 0.05 v. control). A marked increase in the main lipid-soluble antioxidants (α-tocopherol, γ-tocopherol and xanthophyll) was observed following watercress supplementation (P< 0.05 v. control) in both experimental phases. These findings suggest that short- and long-term watercress ingestion has potential antioxidant effects against exercise-induced DNA damage and lipid peroxidation.",
"title": "Acute and chronic watercress supplementation attenuates exercise-induced peripheral mononuclear cell DNA damage and lipid peroxidation."
},
{
"docid": "MED-2471",
"text": "The International Study of Asthma and Allergies in Childhood (ISAAC) Phase One showed large worldwide variations in the prevalence of symptoms of asthma, rhinoconjunctivitis and eczema, up to 10 to 20 fold between countries. Ecological analyses were undertaken with ISAAC Phase One data to explore factors that may have contributed to these variations, and are summarised and reviewed here. In ISAAC Phase One the prevalence of symptoms in the past 12 months of asthma, rhinoconjunctivitis and eczema were estimated from studies in 463,801 children aged 13 - 14 years in 155 centres in 56 countries, and in 257,800 children aged 6-7 years in 91 centres in 38 countries. Ecological analyses were undertaken between symptom prevalence and the following: Gross National Product per capita (GNP), food intake, immunisation rates, tuberculosis notifications, climatic factors, tobacco consumption, pollen, antibiotic sales, paracetamol sales, and outdoor air pollution. Symptom prevalence of all three conditions was positively associated with GNP, trans fatty acids, paracetamol, and women smoking, and inversely associated with food of plant origin, pollen, immunisations, tuberculosis notifications, air pollution, and men smoking. The magnitude of these associations was small, but consistent in direction between conditions. There were mixed associations of climate and antibiotic sales with symptom prevalence. The potential causality of these associations warrant further investigation. Factors which prevent the development of these conditions, or where there is an absence of a positive correlation at a population level may be as important from the policy viewpoint as a focus on the positive risk factors. Interventions based on small associations may have the potential for a large public health benefit.",
"title": "Which population level environmental factors are associated with asthma, rhinoconjunctivitis and eczema? Review of the ecological analyses of ISAAC Phase One"
},
{
"docid": "MED-2484",
"text": "Paediatric asthma is a major clinical concern worldwide and represents a huge burden on family and society. It accounts for a large number of lost school days and may deprive the child of both academic achievement and social interaction. Childhood asthma also places strain on healthcare resources as a result of doctor and hospital visits and the cost of treatment. The prevalence of asthma varies worldwide, possibly because of different exposure to respiratory infection, indoor and outdoor pollution, and diet. Certain risk factors appear to predispose children to developing asthma and atopic disease, including incidence and severity of wheezing, atopy, maternal smoking, and number of fever episodes. This paper discusses the burden, prevalence, and risk factors associated with paediatric asthma.",
"title": "The burden of childhood asthma"
},
{
"docid": "MED-3233",
"text": "Our objective in this study was to determine the effects of a high-protein and high-potential renal acid load (PRAL) diet on calcium (Ca) absorption and retention and markers of bone metabolism. In a randomized crossover design, 16 postmenopausal women consumed 2 diets: 1 with low protein and low PRAL (LPLP; total protein: 61 g/d; PRAL: -48 mEq/d) and 1 with high protein and high PRAL (HPHP; total protein: 118 g/d; PRAL: 33 mEq/d) for 7 wk each separated by a 1-wk break. Ca absorption was measured by whole body scintillation counting of radio-labeled (47)Ca. Compared with the LPLP diet, the HPHP diet increased participants' serum IGF-I concentrations (P < 0.0001), decreased serum intact PTH concentrations (P < 0.001), and increased fractional (47)Ca absorption (mean ± pooled SD: 22.3 vs. 26.5 ± 5.4%; P < 0.05) and urinary Ca excretion (156 vs. 203 ± 63 mg/d; P = 0.005). The net difference between the amount of Ca absorbed and excreted in urine did not differ between 2 diet periods (55 vs. 28 ± 51 mg/d). The dietary treatments did not affect other markers of bone metabolism. In summary, a diet high in protein and PRAL increases the fractional absorption of dietary Ca, which partially compensates for increased urinary Ca, in postmenopausal women. The increased IGF-I and decreased PTH concentrations in serum, with no change in biomarkers of bone resorption or formation, indicate a high-protein diet has no adverse effects on bone health.",
"title": "A diet high in meat protein and potential renal acid load increases fractional calcium absorption and urinary calcium excretion without affecting m..."
},
{
"docid": "MED-3373",
"text": "Objectives. We considered the relationship between an urban adult population's fruit and vegetable consumption and several selected social and psychological processes, beneficial aesthetic experiences, and garden participation. Methods. We conducted a population-based survey representing 436 residents across 58 block groups in Denver, Colorado, from 2006 to 2007. We used multilevel statistical models to evaluate the survey data. Results. Neighborhood aesthetics, social involvement, and community garden participation were significantly associated with fruit and vegetable intake. Community gardeners consumed fruits and vegetables 5.7 times per day, compared with home gardeners (4.6 times per day) and nongardeners (3.9 times per day). Moreover, 56% of community gardeners met national recommendations to consume fruits and vegetables at least 5 times per day, compared with 37% of home gardeners and 25% of nongardeners. Conclusions. Our study results shed light on neighborhood processes that affect food-related behaviors and provides insights about the potential of community gardens to affect these behaviors. The qualities intrinsic to community gardens make them a unique intervention that can narrow the divide between people and the places where food is grown and increase local opportunities to eat better.",
"title": "The Influence of Social Involvement, Neighborhood Aesthetics, and Community Garden Participation on Fruit and Vegetable Consumption"
},
{
"docid": "MED-3453",
"text": "There has been no investigation to determine if the widely used over-the-counter, water-soluble antioxidants vitamin C and N-acetyl-cysteine (NAC) could act as pro-oxidants in humans during inflammatory conditions. We induced an acute-phase inflammatory response by an eccentric arm muscle injury. The inflammation was characterized by edema, swelling, pain, and increases in plasma inflammatory indicators, myeloperoxidase and interleukin-6. Immediately following the injury, subjects consumed a placebo or vitamin C (12.5 mg/kg body weight) and NAC (10 mg/kg body weight) for 7 d. The resulting muscle injury caused increased levels of serum bleomycin-detectable iron and the amount of iron was higher in the vitamin C and NAC group. The concentrations of lactate dehydrogenase (LDH), creatine kinase (CK), and myoglobin were significantly elevated 2, 3, and 4 d postinjury and returned to baseline levels by day 7. In addition, LDH and CK activities were elevated to a greater extent in the vitamin C and NAC group. Levels of markers for oxidative stress (lipid hydroperoxides and 8-iso prostaglandin F2alpha; 8-Iso-PGF2alpha) and antioxidant enzyme activities were also elevated post-injury. The subjects receiving vitamin C and NAC had higher levels of lipid hydroperoxides and 8-Iso-PGF2alpha 2 d after the exercise. This acute human inflammatory model strongly suggests that vitamin C and NAC supplementation immediately post-injury, transiently increases tissue damage and oxidative stress.",
"title": "Supplementation with vitamin C and N-acetyl-cysteine increases oxidative stress in humans after an acute muscle injury induced by eccentric exercise."
},
{
"docid": "MED-3789",
"text": "Background: Meat, milk, and eggs have been inconsistently associated with the risk of advanced prostate cancer. These foods are sources of choline—a nutrient that may affect prostate cancer progression through cell membrane function and one-carbon metabolism. No study has examined dietary choline and the risk of lethal prostate cancer. Objective: Our objective was to examine whether dietary choline, choline-containing compounds, and betaine (a choline metabolite) increase the risk of lethal prostate cancer. Design: We prospectively examined the intake of these nutrients and the risk of lethal prostate cancer among 47,896 men in the Health Professionals Follow-Up Study. In a case-only survival analysis, we examined the postdiagnostic intake of these nutrients and the risk of lethal prostate cancer among 4282 men with an initial diagnosis of nonmetastatic disease during follow-up. Diet was assessed with a validated questionnaire 6 times during 22 y of follow-up. Results: In the incidence analysis, we observed 695 lethal prostate cancers during 879,627 person-years. Men in the highest quintile of choline intake had a 70% increased risk of lethal prostate cancer (HR: 1.70; 95% CI: 1.18, 2.45; P-trend = 0.005). In the case-only survival analysis, we observed 271 lethal cases during 33,679 person-years. Postdiagnostic choline intake was not statistically significantly associated with the risk of lethal prostate cancer (HR for quintile 5 compared with quintile 1: 1.69; 95% CI: 0.93, 3.09; P-trend = 0.20). Conclusion: Of the 47,896 men in our study population, choline intake was associated with an increased risk of lethal prostate cancer.",
"title": "Choline intake and risk of lethal prostate cancer: incidence and survival"
},
{
"docid": "MED-2205",
"text": "AIM: To investigate the effects of proteins purified from sweet potato storage roots on human colorectal cancer cell lines. METHODS: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Hoechst 33258 nuclear staining and Boyden transwell chamber methods were used to determine whether purified sweet potato protein (SPP) from fresh sweet potato roots affected proliferation, migration and invasion, respectively, of human colorectal cancer SW480 cells in vitro. The inhibitory effects of SPP on growth of human colorectal cancer HCT-8 cells intraperitoneally xenografted in nude mice and spontaneous lung metastasis of murine Lewis lung carcinoma 3LL cells subcutaneously transplanted in C57 BL/6 mice were also investigated in vivo. RESULTS: SPP inhibited the proliferation of SW480 cells in a dose-dependent manner, with an IC50 value of 38.732 μmol/L (r2 = 0.980, P = 0.003) in the MTT assay. Hoechst 33258 nuclear staining further revealed inhibition of cell viability and induction of apoptosis by SPP. The transwell assay disclosed significant reduction in migrated cells/field by 8 μmol/L SPP (8.4 ± 2.6 vs 23.3 ± 5.4, P = 0.031) and invaded cells/field through the ECMatrix by 0.8 μmol/L SPP, compared with the control (25.2 ± 5.2 vs 34.8 ± 6.1, P = 0.038). Both intraperitoneal (ip) and intragastric (ig) administration of SPP led to significant suppression of growth of intraperitoneally inoculated HCT-8 cells in nude mice to 58.0% ± 5.9% (P = 0.037) and 43.5% ± 7.1% (P = 0.004) of the controls, respectively, after 9 d treatment. Bloody ascites additionally disappeared after ip injection of trypsin inhibitor. Notably, ig and ip administration of SPP induced a significant decrease in spontaneous pulmonary metastatic nodule formation in C57 BL/6 mice (21.0 ± 12.3 and 27.3 ± 12.7 nodules/lung vs 42.5 ± 4.5 nodules/lung in controls, respectively, P < 0.05) after 25 d treatment. Moreover, the average weight of primary tumor nodules in the hind leg of mice decreased from 8.2 ± 1.3 g/mice in the control to 6.1 ± 1.4 g/mice in the ip group (P = 0.035). CONCLUSION: SPP exerts significant antiproliferative and antimetastatic effects on human colorectal cancer cell lines, both in vitro and in vivo.",
"title": "Anticancer effects of sweet potato protein on human colorectal cancer cells"
},
{
"docid": "MED-3294",
"text": "In the past two decades or so, a number of viruses have emerged in the global swine population. Some, such as porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2), cause economically important diseases in pigs, whereas others such as porcine torque teno virus (TTV), now known as Torque teno sus virus (TTSuV), porcine bocavirus (PBoV) and related novel parvoviruses, porcine kobuvirus, porcine toroviruses (PToV) and porcine lymphotropic herpesviruses (PLHV), are mostly subclinical in swine herds. Although some emerging swine viruses such as swine hepatitis E virus (swine HEV), porcine endogenous retrovirus (PERV) and porcine sapovirus (porcine SaV) may have a limited clinical implication in swine health, they do pose a potential public health concern in humans due to zoonotic (swine HEV) or potential zoonotic (porcine SaV) and xenozoonotic (PERV, PLHV) risks. Other emerging viruses such as Nipah virus, Bungowannah virus and Menangle virus not only cause diseases in pigs but some also pose important zoonotic threat to humans. This article focuses on emerging and re-emerging swine viruses that have a limited or uncertain clinical and economic impact on pig health. The transmission, epidemiology and pathogenic potential of these viruses are discussed. In addition, the two economically important emerging viruses, PRRSV and PCV2, are also briefly discussed to identify important knowledge gaps. © 2012 Blackwell Verlag GmbH.",
"title": "Emerging and re-emerging swine viruses."
},
{
"docid": "MED-1257",
"text": "Meat protein is associated with an increase in risk of heart disease. Recent data have shown that meat protein appeared to be associated with weight gain over 6.5 years, with 1 kg of weight increase per 125 g of meat per day. In the Nurses' Health Study, diets low in red meat, containing nuts, low-fat dairy, poultry, or fish, were associated with a 13% to 30% lower risk of CHD compared with diets high in meat. Low-carbohydrate diets high in animal protein were associated with a 23% higher total mortality rate whereas low-carbohydrate diets high in vegetable protein were associated with a 20% lower total mortality rate. Recent soy interventions have been assessed by the American Heart Association and found to be associated with only small reductions in LDL cholesterol. Although dairy intake has been associated with a lower weight and lower insulin resistance and metabolic syndrome, the only long-term (6 months) dairy intervention performed so far has shown no effects on these parameters.",
"title": "Protein and coronary heart disease: the role of different protein sources."
},
{
"docid": "MED-2364",
"text": "We have recently demonstrated that both antibodies to Gal alpha(1,3)Gal, and the Gal alpha(1,3)Gal binding lectin (IB4), bind a synthetic peptide (DAHWESWL), there being a similar recognition of carbohydrate and peptide structures. We now report that the anti-Gal alpha(1,3)Gal antibodies and IB4 lectin also react with peptides encoded by mucin genes (MUC 1, 3, 4)-sequences known to be rich in serine, threonine and proline. This activity was demonstrated (1) by the ability of mucin derived peptides to block the reaction of anti-Gal alpha(1,3)Gal antibodies and IB4 lectin with a Gal alpha(1,3)Gal+ pig endothelial cell line; the reactions were specific and did not occur with a random peptide containing the same sequences or with other mucin peptides; (2) by the fact that anti-mucin1 antibodies could react with the Gal alpha(1,3)Gal expressed after transfection of COS cells (Gal alpha(1,3)Gal-,Muc1-) with cDNA encoding the pig alpha, 3galactosyltransferase; and (3) that the IB4 lectin and anti-Gal alpha(1,3)Gal antibodies could react with mucin 1 found on the surface of human breast cancer cells. Thus natural occurring anti-Gal alpha(1,3)Gal antibodies found in all human serum can react with self (Muc1) peptides expressed in large amounts on the surface of tumour cells but not on normal cells. The findings are of interest and serve to explain the previously reported findings that human cells can, at times, express Gal alpha(1,3)Gal; such expression is an artefact, the reaction is due to the phenomenon described herein, i.e. that anti-Gal alpha(1,3)Gal antibodies react with mucin peptides.",
"title": "Natural human anti-Gal alpha(1,3)Gal antibodies react with human mucin peptides."
},
{
"docid": "MED-3353",
"text": "Skin blood perfusion and oxygenation depends upon cardiovascular, hormonal and circulatory health in humans and provides socio-sexual signals of underlying physiology, dominance and reproductive status in some primates. We allowed participants to manipulate colour calibrated facial photographs along empirically-measured oxygenated and deoxygenated blood colour axes both separately and simultaneously, to optimise healthy appearance. Participants increased skin blood colour, particularly oxygenated, above basal levels to optimise healthy appearance. We show, therefore, that skin blood perfusion and oxygenation influence perceived health in a way that may be important to mate choice.",
"title": "Skin Blood Perfusion and Oxygenation Colour Affect Perceived Human Health"
},
{
"docid": "MED-3371",
"text": "Background: The overconsumption of energy-dense foods leads to excessive energy intakes. The substitution of low-energy-dense vegetables for foods higher in energy density can help decrease energy intakes but may be difficult to implement if individuals dislike the taste of vegetables. Objective: We investigated whether incorporating puréed vegetables to decrease the energy density of entrées at multiple meals reduced daily energy intakes and increased daily vegetable intakes. Design: In this crossover study, 20 men and 21 women ate ad libitum breakfast, lunch, and dinner in the laboratory once a week for 3 wk. Across conditions, entrées at meals varied in energy density from standard versions (100% condition) to reduced versions (85% and 75% conditions) by the covert incorporation of 3 or 4.5 times the amount of puréed vegetables. Entrées were accompanied by unmanipulated side dishes. Participants rated their hunger and fullness before and after meals. Results: Subjects consumed a consistent weight of foods across conditions of energy density; thus, the daily energy intake significantly decreased by 202 ± 60 kcal in the 85% condition (P < 0.001) and by 357 ± 47 kcal in the 75% condition (P < 0.0001). Daily vegetable consumption significantly increased from 270 ± 17 g of vegetables in the 100% condition to 487 ± 25 g of vegetables in the 75% condition (P < 0.0001). Despite the decreased energy intake, ratings of hunger and fullness did not significantly differ across conditions. Entrées were rated as similar in palatability across conditions. Conclusions: Large amounts of puréed vegetables can be incorporated into various foods to decrease the energy density. This strategy can lead to substantial reductions in energy intakes and increases in vegetable intakes. This trial was registered at clinicaltrials.gov as NCT01165086.",
"title": "Hidden vegetables: an effective strategy to reduce energy intake and increase vegetable intake in adults"
},
{
"docid": "MED-3243",
"text": "OBJECTIVES: Considerable evidence has shown that diet can affect both the incidence and the progression of prostate cancer. The objective of this study was to determine whether men in this situation could make a change to a diet emphasizing plant-based foods and fish and to examine the effect on quality of life (QOL) and prostate-specific antigen (PSA) velocity. METHODS: A total of 36 men and their partners were randomly assigned to attend a series of 11 dietary and cooking classes that also integrated mindfulness practice as a support in making the change or a wait-list control group. Assessments were made of dietary intake, QOL, and PSA at baseline, after intervention (11 weeks), and 3 months after intervention. RESULTS: The intervention group showed significant reductions in the consumption of saturated fat and increased consumption of vegetable proteins with accompanying reductions in animal proteins, including dairy products. They also showed increased QOL. Although no significant change was found in the rate of PSA increase between the two groups, the mean PSA doubling time for the intervention group was substantially longer at the 3-month follow-up visit than that of the controls. CONCLUSIONS: Men with a increasing PSA level after primary treatment were able to make a change to a prostate-healthy diet, accompanied by increases in QOL. No significant difference was found in the log PSA slope between the two groups; however, the PSA doubling time increased substantially in the intervention group compared with that in the controls. Future trials should examine the effect of the prostate-healthy diet with a larger sample of men for a longer period.",
"title": "A dietary intervention for recurrent prostate cancer after definitive primary treatment: results of a randomized pilot trial."
},
{
"docid": "MED-3317",
"text": "Twenty-four patients, all of whom were exposed to aerosolized porcine brain tissue through work-place environment (abattoir), developed a syndrome of immune-mediated polyradiculoneuropathy; three also had central nervous system manifestations (transverse myelitis, meningoencephalitis, and aseptic meningitis). Patients had characteristic electrophysiological findings of very distal and proximal conduction slowing (prolonged distal and F-wave latencies, regions where the blood-nerve barrier is the most permeable) and all patients' serum contained a novel IgG immunofluorescence pattern. Nerve pathology, when available, showed mild changes of segmental demyelination, axonal degeneration, and inflammatory changes. Patients had meaningful improvement of symptoms and electrophysiologic findings with immune therapy and with removal of exposure to aerosolized brain tissue. We postulate that this outbreak is an auto-immune polyradiculoneuropathy triggered by occupational exposure to multiple aerosolized porcine neural tissue antigens that result in neural damage where the blood-nerve barrier is the least robust. © 2011 Peripheral Nerve Society.",
"title": "Auto-immune polyradiculoneuropathy and a novel IgG biomarker in workers exposed to aerosolized porcine brain."
},
{
"docid": "MED-2292",
"text": "In industrialized nations, diverticular disease affects up to 70% of individuals by 60 years of age, with symptoms that can range from mild gastrointestinal disturbance to incapacitating pain. Diverticular disease appears to be related to increasing affluence and changed diet: Current theory holds that diverticular disease's origin is low-fiber diet. This explains why its incidence is highest and accelerating in the more prosperous countries where intake of fiber has decreased and intake of milled grains and refined sugars has increased over time. Not all patients develop symptoms, but if they do, the most frequent complaints associated with diverticulosis are cramping in the left-lower quadrant, bloating, constipation, and soiling. If diverticula perforate the gut's wall into the pericolic tissue, small and large abscesses, accompanied by bleeding, can form. Fistulization, when it occurs, most often penetrates to the bladder. Treatment addresses symptoms and may require hospitalization. During symptomatic periods, patients do best on low-fiber, bland diets. Once the acute episode or highly symptomatic period resolves or chronic disease is managed, patients should gradually increase dietary fiber to 20 to 30 grams daily or take dietary fiber in the form of bulk stimulants like psyllium.",
"title": "Diverticular disease: eat your fiber!"
},
{
"docid": "MED-2354",
"text": "A new natural anti-alpha-galactosyl IgG antibody (anti-Gal) was found to be present in high titer in the serum of every normal individual studied. The antibody was isolated by affinity chromatography on a melibiose-Sepharose column. The reactivity of the antibody was assessed by its interaction with alpha-galactosyl residues on rabbit erythrocytes (RabRBC). The specificity was determined by inhibition experiments with various carbohydrates. The anti-Gal interacts with alpha-galactosyl residues, possibly on glycolipids of human RBC (HuRBC), after removal of membrane proteins by treatment with pronase. In addition, the anti-Gal bind specifically to normal and pathologically senescent HuRBC, suggesting a physiological role for this natural antibody in the aging of RBC. The ubiquitous presence of anti-Gal in high titers throughout life implies a constant antigenic stimulation. In addition to the theoretical interest in the antibody, the study of the anti-Gal reactivity seems to bear immunodiagnostic significance. Decrease in the antibody titer was found to reflect humoral immunodeficiency disorders.",
"title": "A unique natural human IgG antibody with anti-alpha-galactosyl specificity"
},
{
"docid": "MED-3687",
"text": "This study was aimed at determining the probiotic potential of a large number of autochthonous lactic acid bacteria isolated from fruit and vegetables. Survival under simulated gastric and intestinal conditions showed that 35% of the strains, mainly belonging to the species Lactobacillus plantarum maintained high cell densities. Selected strains did not affect the immune-mediation by Caco-2 cells. All strains stimulated all 27 immune-mediators by peripheral blood mononuclear cells (PBMC). A significant (P<0.05; P<0.01) increase of the major part of cytokines and growth factors was found. A few chemokines were stimulated. Immune-mediators with pro-inflammatory activity (IL-17, EOTAXIN and IFNγ) were significantly (P<0.01) stimulated by all strains, followed by IL-1b>IP-10>IL-6>MIP1α. Stimulation of IL-12, IL-2 and IL-7 was strain dependent. Only a few strains increased the synthesis of cytokines with anti-inflammatory activity. Six L. plantarum strains were further selected. Four were defined as the strongly adhesive strains (more than 40 bacteria adhering to one Caco-2 cell), and 2 as the adhesive strains (5-40 bacteria adhering to one Caco-2 cell). Five strains grew and acidified chemically defined medium with fructo-oligosaccharides (FOS) as the only carbon source. End-products of FOS fermentation were found. All strains inhibited enterohemorragic Escherichia coli K12 and Bacillus megaterium F6 isolated from human sources. The results of this study showed that some autochthonous lactic acid bacteria from raw fruit and vegetables have functional features to be considered as novel probiotic candidates. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Novel probiotic candidates for humans isolated from raw fruits and vegetables."
},
{
"docid": "MED-2203",
"text": "Constipation is a common health problem that adversely affects quality of life and the prognosis of hospitalized patients with acute coronary syndromes (ACS). The purpose of this study was to develop and test the sweet potato/footbath/acupressure massage (SFA) intervention as a safe treatment for prevention of constipation and to increase satisfaction with bowel emptying in hospitalized patients with ACS. The study was a prospective, randomized controlled trial with a sample of 93 patients (SFA group, n = 44; usual care group, n = 49). Patients in the SFA group received SFA intervention combined with usual care. The results showed that there were statistical differences between the two groups in terms of (1) the incidence of constipation; (2) the use of laxatives and enemas; (3) patients' subjective satisfaction with their bowel emptying during hospitalization; and (4) sensation of incomplete evacuation and anorectal obstruction/blockade. The SFA intervention was more effective, economical, and practical than usual care alone in managing constipation and satisfaction with defecation in patients hospitalized with ACS.",
"title": "The effect of a sweet potato, footbath, and acupressure intervention in preventing constipation in hospitalized patients with acute coronary syndro..."
},
{
"docid": "MED-2498",
"text": "Dietary restriction (DR) and reduced growth factor signaling both elevate resistance to oxidative stress, reduce macromolecular damage, and increase lifespan in model organisms. In rodents, both DR and decreased growth factor signaling reduce the incidence of tumors and slow down cognitive decline and aging. DR reduces cancer and cardiovascular disease and mortality in monkeys, and reduces metabolic traits associated with diabetes, cardiovascular disease and cancer in humans. Neoplasias and diabetes are also rare in humans with loss of function mutations in the growth hormone receptor. DR and reduced growth factor signaling may thus slow aging by similar, evolutionarily conserved, mechanisms. We review these conserved anti-aging pathways in model organisms, discuss their link to disease prevention in mammals, and consider the negative side effects that might hinder interventions intended to extend healthy lifespan in humans.",
"title": "Dietary Restriction, Growth Factors and Aging: from yeast to humans"
},
{
"docid": "MED-3351",
"text": "Based on evidence that the color red elicits avoidance motivation across contexts (Mehta & Zhu, 2009), two studies investigated the effect of the color red on snack food and soft drink consumption. In line with our hypothesis, participants drank less from a red labeled cup than from a blue labeled cup (Study 1), and ate less snack food from a red plate than from a blue or white plate (Study 2). The results suggest that red functions as a subtle stop signal that works outside of focused awareness and thereby reduces incidental food and drink intake. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "The color red reduces snack food and soft drink intake."
},
{
"docid": "MED-5239",
"text": "Epidemiological evidence points to increased dairy and meat consumption, staples of the Western diet, as major risk factors for the development of type 2 diabetes (T2D). This paper presents a new concept and comprehensive review of leucine-mediated cell signaling explaining the pathogenesis of T2D and obesity by leucine-induced over-stimulation of mammalian target of rapamycin complex 1 (mTORC1). mTORC1, a pivotal nutrient-sensitive kinase, promotes growth and cell proliferation in response to glucose, energy, growth factors and amino acids. Dairy proteins and meat stimulate insulin/insulin-like growth factor 1 signaling and provide high amounts of leucine, a primary and independent stimulator for mTORC1 activation. The downstream target of mTORC1, the kinase S6K1, induces insulin resistance by phosphorylation of insulin receptor substrate-1, thereby increasing the metabolic burden of β-cells. Moreover, leucine-mediated mTORC1-S6K1-signaling plays an important role in adipogenesis, thus increasing the risk of obesity-mediated insulin resistance. High consumption of leucine-rich proteins explains exaggerated mTORC1-dependent insulin secretion, increased β-cell growth and β-cell proliferation promoting an early onset of replicative β-cell senescence with subsequent β-cell apoptosis. Disturbances of β-cell mass regulation with increased β-cell proliferation and apoptosis as well as insulin resistance are hallmarks of T2D, which are all associated with hyperactivation of mTORC1. In contrast, the anti-diabetic drug metformin antagonizes leucine-mediated mTORC1 signaling. Plant-derived polyphenols and flavonoids are identified as natural inhibitors of mTORC1 and exert anti-diabetic and anti-obesity effects. Furthermore, bariatric surgery in obesity reduces increased plasma levels of leucine and other branched-chain amino acids. Attenuation of leucine-mediated mTORC1 signaling by defining appropriate upper limits of the daily intake of leucine-rich animal and dairy proteins may offer a great chance for the prevention of T2D and obesity, as well as other epidemic diseases of civilization with increased mTORC1 signaling, especially cancer and neurodegenerative diseases, which are frequently associated with T2D.",
"title": "Leucine signaling in the pathogenesis of type 2 diabetes and obesity"
},
{
"docid": "MED-3925",
"text": "This study describes how foods rich in fisetin and hexacosanol added to a strict diet reversed most symptoms of Parkinson's disease (PD) in one patient. This is a case report involving outpatient care. The subject was a dietitian diagnosed with idiopathic PD in 2000 at the age of 53 years old, with a history of exposure to neurotoxins and no family history of PD. A basic diet started in 2000 consisted of predominantly fruits, vegetables, 100% whole grains, extra virgin olive oil, nuts, seeds, nonfat milk products, tea, coffee, spices, small amounts of dark chocolate, and less than 25 g of animal fat daily. The basic diet alone failed to prevent decline due to PD. In 2009, the basic diet was enhanced with a good dietary source of both fisetin and hexacosanol. Six months after the patient started the enhanced diet rich in fisetin and hexacosanol, a clinically significant improvement in symptoms was noted; the patient's attending neurologist reported that the clinical presentation of cogwheel rigidity, micrographia, bradykinesia, dystonia, constricted arm swing with gait, hypomimia, and retropulsion appeared to be resolved. The only worsening of symptoms occurred when the diet was not followed precisely. Little improvement in tremor or seborrhea was observed. The clinical improvement has persisted to date. To the best of our knowledge, this is the first case where adjunctive diet therapy resulted in a significant reduction of symptoms of PD without changing the type or increasing the amount of medications.",
"title": "A diet low in animal fat and rich in N-hexacosanol and fisetin is effective in reducing symptoms of Parkinson's disease."
},
{
"docid": "MED-3773",
"text": "The present study assessed the effects of mild dehydration on cognitive performance and mood of young males. A total of twenty-six men (age 20·0 (sd 0·3) years) participated in three randomised, single-blind, repeated-measures trials: exercise-induced dehydration plus a diuretic (DD; 40 mg furosemide); exercise-induced dehydration plus placebo containing no diuretic (DN); exercise while maintaining euhydration plus placebo (EU; control condition). Each trial included three 40 min treadmill walks at 5·6 km/h, 5 % grade in a 27·7°C environment. A comprehensive computerised six-task cognitive test battery, the profile of mood states questionnaire and the symptom questionnaire (headache, concentration and task difficulty) were administered during each trial. Paired t tests compared the DD and DN trials resulting in >1 % body mass loss (mean 1·59 (sd 0·42) %) with the volunteer's EU trial (0·01 (sd 0·03) %). Dehydration degraded specific aspects of cognitive performance: errors increased on visual vigilance (P = 0·048) and visual working memory response latency slowed (P = 0·021). Fatigue and tension/anxiety increased due to dehydration at rest (P = 0·040 and 0·029) and fatigue during exercise (P = 0·026). Plasma osmolality increased due to dehydration (P < 0·001) but resting gastrointestinal temperature was not altered (P = 0·238). In conclusion, mild dehydration without hyperthermia in men induced adverse changes in vigilance and working memory, and increased tension/anxiety and fatigue.",
"title": "Mild dehydration impairs cognitive performance and mood of men."
},
{
"docid": "MED-3354",
"text": "The luminance contrast between facial features and facial skin is greater in women than in men, and women's use of make-up enhances this contrast. In black-and-white photographs, increased luminance contrast enhances femininity and attractiveness in women's faces, but reduces masculinity and attractiveness in men's faces. In Caucasians, much of the contrast between the lips and facial skin is in redness. Red lips have been considered attractive in women in geographically and temporally diverse cultures, possibly because they mimic vasodilation associated with sexual arousal. Here, we investigate the effects of lip luminance and colour contrast on the attractiveness and sex typicality (masculinity/femininity) of human faces. In a Caucasian sample, we allowed participants to manipulate the colour of the lips in colour-calibrated face photographs along CIELab L* (light--dark), a* (red--green), and b* (yellow--blue) axes to enhance apparent attractiveness and sex typicality. Participants increased redness contrast to enhance femininity and attractiveness of female faces, but reduced redness contrast to enhance masculinity of men's faces. Lip blueness was reduced more in female than male faces. Increased lightness contrast enhanced the attractiveness of both sexes, and had little effect on perceptions of sex typicality. The association between lip colour contrast and attractiveness in women's faces may be attributable to its association with oxygenated blood perfusion indicating oestrogen levels, sexual arousal, and cardiac and respiratory health.",
"title": "Lip colour affects perceived sex typicality and attractiveness of human faces."
},
{
"docid": "MED-5197",
"text": "BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) and heterocyclic amines (HCAs) are carcinogens formed in or on the surface of well-done meat, cooked at high temperature. METHODS: We estimated breast cancer risk in relation to intake of cooked meat in a population-based, case-control study (1508 cases and 1556 controls) conducted in Long Island, NY from 1996 to 1997. Lifetime intakes of grilled or barbecued and smoked meats were derived from the interviewer-administered questionnaire data. Dietary intakes of PAH and HCA were derived from the self-administered modified Block food frequency questionnaire of intake 1 year before reference date. Unconditional logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Modest increased risk was observed among postmenopausal, but not premenopausal, women consuming the most grilled or barbecued and smoked meats over the life course (OR = 1.47; CI = 1.12-1.92 for highest vs. lowest tertile of intake). Postmenopausal women with low fruit and vegetable intake, but high lifetime intake of grilled or barbecued and smoked meats, had a higher OR of 1.74 (CI = 1.20-2.50). No associations were observed with the food frequency questionnaire-derived intake measures of PAHs and HCAs, with the possible exception of benzo(alpha)pyrene from meat among postmenopausal women whose tumors were positive for both estrogen receptors and progesterone receptors (OR = 1.47; CI = 0.99-2.19). CONCLUSIONS: These results support the accumulating evidence that consumption of meats cooked by methods that promote carcinogen formation may increase risk of postmenopausal breast cancer.",
"title": "Cooked meat and risk of breast cancer--lifetime versus recent dietary intake."
},
{
"docid": "MED-3933",
"text": "In this study, the effects of a diet rich in insoluble fiber (DRIF) on motor disability and the peripheral pharmacokinetics of orally administered L-dopa in Parkinsonian patients with marked constipation are analyzed. We found a useful effect of a DRIF on plasma L-dopa concentration and motor function. The greatest effect on the plasma L-dopa levels was found early (at 30 and 60 min) after oral administration. There was a relationship between the improvement of constipation and the higher bioavailability of L-dopa. DRIF can be a coadjuvant treatment in patients with Parkinson's disease.",
"title": "Clinical and pharmacokinetic effects of a diet rich in insoluble fiber on Parkinson disease."
},
{
"docid": "MED-2831",
"text": "TNFs are major mediators of inflammation and inflammation-related diseases, hence, the United States Food and Drug Administration (FDA) has approved the use of blockers of the cytokine, TNF-α, for the treatment of osteoarthritis, inflammatory bowel disease, psoriasis and ankylosis. These drugs include the chimeric TNF antibody (infliximab), humanized TNF-α antibody (Humira) and soluble TNF receptor-II (Enbrel) and are associated with a total cumulative market value of more than $20 billion a year. As well as being expensive ($15 000–20 000 per person per year), these drugs have to be injected and have enough adverse effects to be given a black label warning by the FDA. In the current report, we describe an alternative, curcumin (diferuloylmethane), a component of turmeric (Curcuma longa) that is very inexpensive, orally bioavailable and highly safe in humans, yet can block TNF-α action and production in in vitro models, in animal models and in humans. In addition, we provide evidence for curcumin's activities against all of the diseases for which TNF blockers are currently being used. Mechanisms by which curcumin inhibits the production and the cell signalling pathways activated by this cytokine are also discussed. With health-care costs and safety being major issues today, this golden spice may help provide the solution. Linked Articles This article is part of a themed section on Emerging Therapeutic Aspects in Oncology. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.169.issue-8",
"title": "Curcumin: an orally bioavailable blocker of TNF and other pro-inflammatory biomarkers"
},
{
"docid": "MED-2448",
"text": "A double-blind comparative study was conducted on cedar pollinosis patients in order to evaluate the treatment efficacy of apple polyphenol (Ap). Ap was administered (500 mg) once daily for 12 weeks, starting about 2 weeks prior to cedar pollen dispersion. Pollinosis symptoms during the study were evaluated according to the classification in the guidelines for allergic rhinitis diagnosis and treatment. The results show that the sneezing score was significantly lower for the Ap group than with the placebo group during the early period of pollen dispersion and during the main dispersion period. In addition, no adverse reactions were induced by Ap during the study. These results suggest that Ap may alleviate the symptoms of cedar pollinosis.",
"title": "Clinical efficacy of apple polyphenol for treating cedar pollinosis."
},
{
"docid": "MED-2365",
"text": "Twenty-five patients living in a tick-endemic region of Sydney, New South Wales developed red meat allergy after experiencing large local reactions to tick bites. This represents a potentially novel cross-reaction between an arthropod and a food protein. (MJA 2009; 190: 510-511).",
"title": "An association between tick bite reactions and red meat allergy in humans."
},
{
"docid": "MED-3307",
"text": "OBJECTIVE: workers in slaughterhouses and processing plants that handle pigs, and pork butchers/meatcutters have been little studied for health risks associated with employment, in spite of the fact that they are potentially exposed to oncogenic and non-oncogenic transmissible agents and chemical carcinogens at work. We report here on an update of mortality in 510 workers employed in abattoirs and processing plants that almost exclusively handled pigs and pork products. METHODS: standardized mortality ratios (SMRs) were estimated for the cohort as a whole, and in subgroups defined by race and sex, using the corresponding US general population mortality rates for comparison. Study subjects were followed up from January 1950 to December 2006, during which time 45% of them died. RESULTS: mortality was significantly increased overall in the cohort. A statistically significant excess of deaths was observed for colon and lung cancers in the entire cohort, SMR=2.7 (95% CI, 1.2-5.1), SMR=1.8 (95% CI, 1.1-2.7), respectively. Significant SMRs in the cohort as a whole were also observed for senile and pre-senile psychotic conditions (SMR=5.1, 95% CI, 1.4-13.1), and pneumonia (SMR=2.6, 95% CI, 1.3-4.8). An observed excess of subarachnoid hemorrhage was seen mainly in whites (SMR=10.1, 95% CI, 1.2-36.3). There was a suggestion of an excess of deaths from ischemic heart disease also, but the elevated SMR was confined to men and was not statistically significant. CONCLUSION: this study confirms the excess occurrence of lung and colon cancers, and stroke previously reported in this occupational group. New findings are the excess of risk for senile and pre-senile psychotic conditions and pneumonia, which together with the excess of colon cancer appear specific for pig/pork workers, as they were not evident in much larger studies of workers in abattoirs and processing plants handling cattle and sheep. However, caution should be exercised in interpreting these findings, since some of them could have occurred by chance, resulting from our examination of a large number of causes of death in multiple study subgroups. For the moment, the significance of these findings remains unknown until they are confirmed in larger studies of adequate statistical power. Studies that will take into account possible occupational and non-occupational confounding factors are needed. Copyright © 2011. Published by Elsevier Inc.",
"title": "Mortality in workers employed in pig abattoirs and processing plants."
},
{
"docid": "MED-3280",
"text": "Conventional chemotherapies have showed their limits, notably for patients with advanced cancer. New therapeutic strategies must be identified, and the metabolic abnormalities of cancer cells offer such opportunities. Many human cancer cell lines and primary tumors have absolute requirements for methionine, an essential amino acid. In contrast, normal cells are relatively resistant to exogenous methionine restriction. The biochemical mechanism for methionine dependency has been studied extensively, but the fundamental mechanism remains unclear. A number of investigators have attempted to exploit the methionine dependence of tumors for therapeutic effects in vivo. To reduce in vivo methionine in plasma and tumours, dietary and pharmacological treatments have been used. Methionine-free diet or methionine-deprived total parenteral nutrition causes regression of a variety of animal tumours. Alternatively, methionine depletion was achieved by the use of methioninase. This enzyme specifically degrades methionine and inhibits tumour growth in preclinical models. Because of potential toxicity and quality of life problems, prolonged methionine restriction with diet or with methioninase is not suitable for clinical use. Methionine restriction may find greater application in association with various chemotherapeutic agents. Several preclinical studies have demonstrated synergy between methionine restriction and various cytotoxic chemotherapy drugs. The experimental results accumulated during the last three decades suggest that methionine restriction can become an additional cancer therapeutic strategy, notably in association with chemotherapy.",
"title": "Methionine dependency and cancer treatment."
},
{
"docid": "MED-3137",
"text": "A longstanding goal of dietary surveillance has been to estimate the proportion of the population with intakes above or below a target, such as a recommended level of intake. However, until now, statistical methods for assessing the alignment of food intakes with recommendations have been lacking. The purposes of this study were to demonstrate the National Cancer Institute’s method of estimating the distribution of usual intake of foods and determine the proportion of the U.S. population who does not meet federal dietary recommendations. Data were obtained from the 2001–2004 NHANES for 16,338 persons, aged 2 y and older. Quantities of foods reported on 24-h recalls were translated into amounts of various food groups using the MyPyramid Equivalents Database. Usual dietary intake distributions were modeled, accounting for sequence effect, weekend/weekday effect, sex, age, poverty income ratio, and race/ethnicity. The majority of the population did not meet recommendations for all of the nutrient-rich food groups, except total grains and meat and beans. Concomitantly, overconsumption of energy from solid fats, added sugars, and alcoholic beverages (“empty calories”) was ubiquitous. Over 80% of persons age ≥71 y and over 90% of all other sex-age groups had intakes of empty calories that exceeded the discretionary calorie allowances. In conclusion, nearly the entire U.S. population consumes a diet that is not on par with recommendations. These findings add another piece to the rather disturbing picture that is emerging of a nation’s diet in crisis.",
"title": "Americans Do Not Meet Federal Dietary Recommendations"
},
{
"docid": "MED-4921",
"text": "BACKGROUND & AIMS: The diagnostic criteria for celiac disease require small-bowel mucosal villous atrophy with crypt hyperplasia (Marsh III). However, mucosal damage develops gradually and patients may evince clinical symptoms before histologic changes appear. Endomysial antibodies are specific in predicting forthcoming villous atrophy. We hypothesized that patients with mild enteropathy but positive endomysial antibodies benefit from a gluten-free diet (GFD) similarly to patients with more severe enteropathy. METHODS: Small-bowel endoscopy together with clinical evaluations was performed in all together 70 consecutive adults with positive endomysial antibodies. Of these, 23 had only mild enteropathy (Marsh I-II) and they were randomized either to continue on a gluten-containing diet or start a GFD. After 1 year, clinical, serologic, and histologic evaluations were repeated. A total of 47 participants had small-bowel mucosal lesions compatible with celiac disease (Marsh III), and these served as disease controls. RESULTS: In the gluten-containing diet group (Marsh I-II) the small-bowel mucosal villous architecture deteriorated in all participants, and the symptoms and abnormal antibody titers persisted. In contrast, in the GFD group (Marsh I-II) the symptoms were alleviated, antibody titers decreased, and mucosal inflammation diminished equally to celiac controls (Marsh III). When the trial was completed, all participants chose to continue on a life-long GFD. CONCLUSIONS: Patients with endomysial antibodies benefit from a GFD regardless of the degree of enteropathy. The diagnostic criteria for celiac disease need re-evaluation: endomysial antibody positivity without atrophy belongs to the spectrum of genetic gluten intolerance, and warrants dietary treatment.",
"title": "Diagnosing mild enteropathy celiac disease: a randomized, controlled clinical study."
},
{
"docid": "MED-1256",
"text": "BACKGROUND: Limited consumption of red meat, including beef, is one of many often-suggested strategies to reduce the risk of coronary heart disease (CHD). However, the role that beef consumption specifically plays in promoting adverse changes in the cardiovascular risk factor profile is unclear. OBJECTIVE: A meta-analysis of randomized, controlled, clinical trials (RCTs) was conducted to evaluate the effects of beef, independent of other red and processed meats, compared with poultry and/or fish consumption, on lipoprotein lipids. METHODS: RCTs published from 1950 to 2010 were considered for inclusion. Studies were included if they reported fasting lipoprotein lipid changes after beef and poultry/fish consumption by subjects free of chronic disease. A total of 124 RCTs were identified, and 8 studies involving 406 subjects met the prespecified entry criteria and were included in the analysis. RESULTS: Relative to the baseline diet, mean ± standard error changes (in mg/dL) after beef versus poultry/fish consumption, respectively, were -8.1 ± 2.8 vs. -6.2 ± 3.1 for total cholesterol (P = .630), -8.2 ± 4.2 vs. -8.9 ± 4.4 for low-density lipoprotein cholesterol (P = .905), -2.3 ± 1.0 vs. -1.9 ± 0.8 for high-density lipoprotein cholesterol (P = .762), and -8.1 ± 3.6 vs. -12.9 ± 4.0 mg/dL for triacylglycerols (P = .367). CONCLUSION: Changes in the fasting lipid profile were not significantly different with beef consumption compared with those with poultry and/or fish consumption. Inclusion of lean beef in the diet increases the variety of available food choices, which may improve long-term adherence with dietary recommendations for lipid management. Copyright © 2012 National Lipid Association. Published by Elsevier Inc. All rights reserved.",
"title": "A meta-analysis of randomized controlled trials that compare the lipid effects of beef versus poultry and/or fish consumption."
},
{
"docid": "MED-4680",
"text": "OBJECTIVE: To investigate associations between dietary intakes throughout childhood and age at menarche, a possible indicator of future risk of disease, in a contemporary cohort of British girls. DESIGN: Diet was assessed by FFQ at 3 and 7 years of age, and by a 3 d unweighed food diary at 10 years. Age at menarche was categorised as before or after 12 years 8 months, a point close to the median age in this cohort. SETTING: Bristol, South-West England. SUBJECTS: Girls (n 3298) participating in the Avon Longitudinal Study of Parents and Children. RESULTS: Higher energy intakes at 10 years were positively associated with the early occurrence of menarche, but this association was removed on adjusting for body size. Total and animal protein intakes at 3 and 7 years were positively associated with age at menarche ≤12 years 8 months (adjusted OR for a 1 sd increase in protein at 7 years: 1·14 (95 % CI 1·04, 1·26)). Higher PUFA intakes at 3 and 7 years were also positively associated with early occurrence of menarche. Meat intake at 3 and 7 years was strongly positively associated with reaching menarche by 12 years 8 months (OR for menarche in the highest v. lowest category of meat consumption at 7 years: 1·75 (95 % CI 1·25, 2·44)). CONCLUSIONS: These data suggest that higher intakes of protein and meat in early to mid-childhood may lead to earlier menarche. This may have implications for the lifetime risk of breast cancer and osteoporosis.",
"title": "Diet throughout childhood and age at menarche in a contemporary cohort of British girls."
},
{
"docid": "MED-3244",
"text": "Diet may represent a modifiable prostate cancer (CaP) risk factor, but a vegetable-based prostate-healthy diet is a major change for most men. We used a ratio of animal:vegetable proteins (A:V ratio) to evaluate whether a comprehensive dietary change was self-sustaining following completion of 11 weekly dietary and cooking classes that integrated mindfulness training (MT). Thirty-six men with recurring CaP were randomized to the intervention or wait-list control. Assessments were at baseline, three months and six months. Of the 17 men randomized to the intervention, 14 completed the requirements. Nineteen were randomized to control and 17 completed requirements. Compared to controls, a significant post-intervention (3 months) decrease in A:V ratio in the intervention group (p=.01) was self-maintained 3 months post-intervention (p=0.049). At each assessment, the A:V ratio was correlated with lycopene, fiber, saturated fat, and dietary cholesterol; four dietary components linked to clinically relevant outcomes in CaP. Change in A:V ratio was also significantly correlated with changes in fiber, saturated fat and dietary cholesterol intake. Participants reported regular MT practice and there was a significant correlation between MT practice and changes in both initiation and maintenance of the change in the A:V ratio. These pilot results provide encouraging evidence for the feasibility of a dietary program that includes MT in supporting dietary change for men with recurrent CaP and invite further study to explore the possible role of MT as a means of supporting both initiation of dietary changes and maintenance of those changes over time.",
"title": "A Novel Measure of Dietary Change in a Prostate Cancer Dietary Program Incorporating Mindfulness Training"
},
{
"docid": "MED-1230",
"text": "This study examined the relationship between funding sources and the outcomes of published obesity-related research. A list of funded projects for human nutrition research linking food intake to obesity in 2001-2005 was drawn from two distinct sources: (a) the federal government's semi-public generic commodity promotion or \"checkoff\" programs for Fluid Milk and Dairy and (b) the National Institutes of Health (NIH). The Principal Investigator for each funded project was determined. Published literature by that individual was located using an Ovid MEDLINE and PubMed author search. All articles related to both dairy and obesity were included. Financial sponsorship for each article and article conclusions were classified by independent groups of co-investigators. Seventy-nine relevant articles were included in the study. Of these, 62 were sponsored by the checkoff programs and 17 by the NIH. The study did not find consistent evidence that checkoff-funded projects were more likely to support an obesity prevention benefit from dairy consumption. The study did identify a new research methodology for the investigation of bias by source of sponsorship. Copyright © 2012 Elsevier Inc. All rights reserved.",
"title": "Relationship between funding sources and outcomes of obesity-related research."
},
{
"docid": "MED-3000",
"text": "An increased risk for colorectal cancer has been consistently reported for long-time consumption of cooked and processed red meat. This has frequently been attributed to chemical carcinogens arising during the cooking process of meat. Long-time fish or poultry consumption apparently does not increase the risk, although similar or higher concentrations of chemical carcinogens were recorded in their preparation for consumption. The geographic epidemiology of colorectal cancer seems to correspond to regions with a high rate of beef consumption. Countries with a virtual absence of beef in the diet (India) or where preferably lamb or goat meat is consumed (several Arabic countries) reveal low rates of colorectal cancer. In China, pork consumption has a long tradition, with an intermediate colorectal cancer rate. In Japan and Korea, large scale beef and pork imports started after World War II or after the Korean War. A steep rise in colorectal cancer incidence was noted after 1970 in Japan and 1990 in Korea. The consumption of undercooked beef (e.g., shabu-shabu, Korean yukhoe and Japanese yukke) became very popular in both countries. The available data are compatible with the interpretation that a specific beef factor, suspected to be one or more thermoresistant potentially oncogenic bovine viruses (e.g., polyoma-, papilloma- or possibly single-stranded DNA viruses) may contaminate beef preparations and lead to latent infections in the colorectal tract. Preceding, concomitant or subsequent exposure to chemical carcinogens arising during cooking procedures should result in increased risk for colorectal cancer synergistic with these infections. Copyright © 2011 UICC.",
"title": "Red meat consumption and cancer: reasons to suspect involvement of bovine infectious factors in colorectal cancer."
},
{
"docid": "MED-3274",
"text": "Objective To determine whether dogs can be trained to identify people with bladder cancer on the basis of urine odour more successfully than would be expected by chance alone. Design Experimental, “proof of principle” study in which six dogs were trained to discriminate between urine from patients with bladder cancer and urine from diseased and healthy controls and then evaluated in tests requiring the selection of one bladder cancer urine sample from six controls. Participants 36 male and female patients (age range 48-90 years) presenting with new or recurrent transitional cell carcinoma of the bladder (27 samples used for training; 9 used for formal testing); 108 male and female controls (diseased and healthy, age range 18-85 years—54 samples used in training; 54 used for testing). Main outcome measure Mean proportion of successes per dog achieved during evaluation, compared with an expected value of 1 in 7 (14%). Results Taken as a group, the dogs correctly selected urine from patients with bladder cancer on 22 out of 54 occasions. This gave a mean success rate of 41% (95% confidence intervals 23% to 58% under assumptions of normality, 26% to 52% using bootstrap methods), compared with 14% expected by chance alone. Multivariate analysis suggested that the dogs' capacity to recognise a characteristic bladder cancer odour was independent of other chemical aspects of the urine detectable by urinalysis. Conclusions Dogs can be trained to distinguish patients with bladder cancer on the basis of urine odour more successfully than would be expected by chance alone. This suggests that tumour related volatile compounds are present in urine, imparting a characteristic odour signature distinct from those associated with secondary effects of the tumour, such as bleeding, inflammation, and infection.",
"title": "Olfactory detection of human bladder cancer by dogs: proof of principle study"
},
{
"docid": "MED-2469",
"text": "The intestinal flora is considered to have an impact on the development of the immune system. In the anthroposophic lifestyle, a diet comprising vegetables spontaneously fermented by lactobacilli, and a restrictive use of antibiotics, anti-pyretics and vaccinations, is typical. The aim of this study was to assess the gut flora in infants in relation to certain lifestyle characteristics associated with anthroposophy. Sixty-nine children < 2 years of age with an anthroposophic lifestyle, and 59 infants of a similar age with a traditional lifestyle, were clinically examined and questionnaire replies assessed. Fecal samples were analyzed by bacterial enumeration, bacterial typing through biochemical fingerprinting and by measuring microflora-associated characteristics (MACs). The numbers of colony-forming units (CFU)/g of feces were significantly higher for enterococci and lactic acid bacteria in children who had never been exposed to antibiotics (5.5 x 107 vs. 2.1 x 107; p < 0.001 and 10 x 107 vs. 4.1 x 107; p < 0.01, respectively). Furthermore, the number of enterococci was significantly higher in breastfed and vegetarian infants (p < 0.01). The diversity (Simpson's diversity index) of lactobacilli, as determined by biochemical fingerprinting, was higher in infants born at home than in those born in hospital (p < 0.01). Several MACs were related to specific lifestyle features, and infants with an anthroposophic lifestyle had a higher proportion of acetic acid and a lower proportion of propionic acid in their stool as compared to the control children. In conclusion, lifestyle factors related to the anthroposophic way of life influenced the composition of the gut flora in the infants. These differences may contribute to the lower prevalence of atopic disease previously observed in children in anthroposophic families.",
"title": "An anthroposophic lifestyle and intestinal microflora in infancy."
},
{
"docid": "MED-3785",
"text": "PURPOSE: Components of one-carbon metabolism are believed to influence cancer development with suggested mechanisms, including DNA methylation and DNA repair mechanisms. However, few prospective studies have investigated one-carbon metabolism in relation to prostate cancer risk, and the results have been conflicting. The aim of this study was to do a comprehensive investigation of the components of one-carbon metabolism in relation to prostate cancer risk. A panel of seven circulating B vitamins and related metabolites was selected, most of which have not been studied before. MATERIALS AND METHODS: We analyzed plasma concentrations of betaine, choline, cysteine, methionine, methylmalonic acid (MMA), vitamin B2, and vitamin B6 in 561 cases and 1,034 controls matched for age and recruitment date, nested within the population-based Northern Sweden Health and Disease Cohort. Relative risks of prostate cancer were estimated by conditional logistic regression. RESULTS: Positive associations with prostate cancer risk were observed for choline and vitamin B2, and an inverse association was observed for MMA. The relative risks for a doubling in concentrations were 1.46 [95% confidence interval (95% CI), 1.04-2.05; P(trend) = 0.03] for choline, 1.11 (95% CI, 1.00-1.23; P(trend) = 0.04) for vitamin B2, and 0.78 (95% CI, 0.63-0.97; P(trend) = 0.03) for MMA. Concentrations of betaine, cysteine, methionine, and vitamin B6 were not associated with prostate cancer risk. CONCLUSION: The results of this large prospective study suggest that elevated plasma concentrations of choline and vitamin B2 may be associated with an increased risk of prostate cancer. These novel findings support a role of one-carbon metabolism in prostate cancer etiology and warrant further investigation.",
"title": "One-carbon metabolism and prostate cancer risk: prospective investigation of seven circulating B vitamins and metabolites."
},
{
"docid": "MED-3350",
"text": "Normotensive adults on low-sodium, weight-loss, and control diets recorded preferences and perceived saltiness for sodium chloride (NaCl) added to cream soup at intervals over 1 yr. Reduction in sodium intake and excretion accompanied a shift in preference toward less salt: preferred concentrations by ad libitum salting declined from 0.72% at the onset to 0.33% NaCl at week 24; hedonic scores for high concentrations of NaCl decreased significantly while scores for low concentrations increased. After 3 mo of sodium restriction, NaCl preferences readjusted to a lower level: ad libitum additions of NaCl were similar after 13, 24, and 52 wk. Less hedonic variation was observed among controls than among Na-restricted groups. The weight-loss group showed increased liking for mid-range NaCl levels. Mechanisms underlying preference changes, including physiological, behavioral, and context effects, may provide insights into maintenance of low-sodium diets for treatment and prevention of hypertension.",
"title": "Effect of dietary sodium restriction on taste responses to sodium chloride: a longitudinal study."
},
{
"docid": "MED-1720",
"text": "BACKGROUND: Insulin-like growth factor (IGF)-I and its main binding protein, IGFBP-3, modulate cell growth and survival, and are thought to be important in tumour development. Circulating concentrations of IGF-I might be associated with an increased risk of cancer, whereas IGFBP-3 concentrations could be associated with a decreased cancer risk. METHODS: We did a systematic review and meta-regression analysis of case-control studies, including studies nested in cohorts, of the association between concentrations of IGF-I and IGFBP-3 and prostate, colorectal, premenopausal and postmenopausal breast, and lung cancer. Study-specific dose-response slopes were obtained by relating the natural log of odds ratios for different exposure levels to blood concentrations normalised to a percentile scale. FINDINGS: We identified 21 eligible studies (26 datasets), which included 3609 cases and 7137 controls. High concentrations of IGF-I were associated with an increased risk of prostate cancer (odds ratio comparing 75th with 25th percentile 1.49, 95% CI 1.14-1.95) and premenopausal breast cancer (1.65, 1.26-2.08) and high concentrations of IGFBP-3 were associated with increased risk of premenopausal breast cancer (1.51, 1.01-2.27). Associations were larger in assessments of plasma samples than in serum samples, and in standard case-control studies compared with nested studies. INTERPRETATION: Circulating concentrations of IGF-I and IGFBP-3 are associated with an increased risk of common cancers, but associations are modest and vary between sites. Although laboratory methods need to be standardised, these epidemiological observations could have major implications for assessment of risk and prevention of cancer.",
"title": "Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis."
},
{
"docid": "MED-2517",
"text": "Many experts in the biology of ageing believe that pharmacological interventions to slow ageing are a matter of ‘when’ rather than ‘if’. A leading target for such interventions is the nutrient response pathway defined by the mechanistic target of rapamycin (mTOR). Inhibition of this pathway extends lifespan in model organisms and confers protection against a growing list of age-related pathologies. Characterized inhibitors of this pathway are already clinically approved, and others are under development. Although adverse side effects currently preclude use in otherwise healthy individuals, drugs that target the mTOR pathway could one day become widely used to slow ageing and reduce age-related pathologies in humans.",
"title": "mTOR is a key modulator of ageing and age-related disease"
},
{
"docid": "MED-4831",
"text": "Dyslipidemia is a primary risk factor for cardiovascular disease, peripheral vascular disease, and stroke. Current guidelines recommend diet as first-line therapy for patients with elevated plasma cholesterol concentrations. However, what constitutes an optimal dietary regimen remains a matter of controversy. Large prospective trials have demonstrated that populations following plant-based diets, particularly vegetarian and vegan diets, are at lower risk for ischemic heart disease mortality. The investigators therefore reviewed the published scientific research to determine the effectiveness of plant-based diets in modifying plasma lipid concentrations. Twenty-seven randomized controlled and observational trials were included. Of the 4 types of plant-based diets considered, interventions testing a combination diet (a vegetarian or vegan diet combined with nuts, soy, and/or fiber) demonstrated the greatest effects (up to 35% plasma low-density lipoprotein cholesterol reduction), followed by vegan and ovolactovegetarian diets. Interventions allowing small amounts of lean meat demonstrated less dramatic reductions in total cholesterol and low-density lipoprotein levels. In conclusion, plant-based dietary interventions are effective in lowering plasma cholesterol concentrations.",
"title": "Effects of plant-based diets on plasma lipids."
},
{
"docid": "MED-3143",
"text": "BACKGROUND: Olestra is a nonabsorbable, energy-free fat substitute. Because it is not absorbed, it may cause digestive symptoms when consumed in large amounts. OBJECTIVE: To compare the frequency and impact of gastrointestinal symptoms in adults and children who freely consume snacks containing olestra or regular snacks in the home. DESIGN: 6-week, double-blind, randomized, parallel, placebo-controlled trial. SETTING: General community. PARTICIPANTS: 3181 volunteers 2 to 89 years of age. INTERVENTION: Households received identical packages labeled as containing olestra corn or potato chips. These packages contained either olestra or regular chips (control). MEASUREMENT: Gastrointestinal symptoms and their impact on daily activities were reported in a daily record. RESULTS: At least one gastrointestinal symptom was reported by 619 of 1620 (38.2%) persons in the olestra group and 576 of 1561 (36.9%) controls (difference, 1.3 percentage points [95% CI, -3.6 to 6.2 percentage points]; P = 0.60). In general, the groups did not differ significantly in the proportion of participants who reported individual gastrointestinal symptoms; however, more controls reported nausea (8.4% compared with 5.7%; difference, -2.7 percentage points [CI, -4.9 to -0.4 percentage points]; P = 0.02). The only difference between groups for the mean numbers of days on which symptoms were reported was that participants in the olestra group had 1 more symptom-day of more frequent bowel movements than did controls (3.7 symptom-days compared with 2.8 symptom days; difference, 0.9 symptom-days [CI, 0.1 to 1.8 symptom-days]; P = 0.04). The groups did not differ in the impact of symptoms on daily activities. CONCLUSIONS: Clinically meaningful or bothersome gastrointestinal effects are not associated with unregulated consumption of olestra corn and potato chips in the home.",
"title": "Gastrointestinal symptoms in 3181 volunteers ingesting snack foods containing olestra or triglycerides. A 6-week randomized, placebo-controlled trial."
},
{
"docid": "MED-4261",
"text": "BACKGROUND: Meat intake may be related to weight gain because of its high energy and fat content. Some observational studies have shown that meat consumption is positively associated with weight gain, but intervention studies have shown mixed results. OBJECTIVE: Our objective was to assess the association between consumption of total meat, red meat, poultry, and processed meat and weight gain after 5 y of follow-up, on average, in the large European population who participated in the European Prospective Investigation into Cancer and Nutrition-Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating Out of Home and Obesity (EPIC-PANACEA) project. DESIGN: A total of 103,455 men and 270,348 women aged 25-70 y were recruited between 1992 and 2000 in 10 European countries. Diet was assessed at baseline with the use of country-specific validated questionnaires. A dietary calibration study was conducted in a representative subsample of the cohort. Weight and height were measured at baseline and self-reported at follow-up in most centers. Associations between energy from meat (kcal/d) and annual weight change (g/y) were assessed with the use of linear mixed models, controlled for age, sex, total energy intake, physical activity, dietary patterns, and other potential confounders. RESULTS: Total meat consumption was positively associated with weight gain in men and women, in normal-weight and overweight subjects, and in smokers and nonsmokers. With adjustment for estimated energy intake, an increase in meat intake of 250 g/d (eg, one steak at approximately 450 kcal) would lead to a 2-kg higher weight gain after 5 y (95% CI: 1.5, 2.7 kg). Positive associations were observed for red meat, poultry, and processed meat. CONCLUSION: Our results suggest that a decrease in meat consumption may improve weight management.",
"title": "Meat consumption and prospective weight change in participants of the EPIC-PANACEA study."
},
{
"docid": "MED-2830",
"text": "OBJECTIVE: The aim of this work was to determine the bioavailability of herbs and spices after human consumption by measuring the ability to protect lymphocytes from an oxidative injury and by examining the impact on inflammatory biomarkers in activated THP-1 cells. METHODS: Ten to 12 subjects in each of 13 groups consumed a defined amount of herb or spice for 7 days. Blood was drawn from subjects before consumption and 1 hour after taking the final herb or spice capsules. Subject serum and various extractions of the herbs and spices were analyzed for antioxidant capacity by oxygen radical absorbance capacity (ORAC) analysis or by 1,1-diphenyl-2-picrylhydrzyl (DPPH). Subject peripheral blood mononuclear cells (PBMCs) in medium with10% autologous serum were incubated with hydrogen peroxide to induce DNA strand breaks. Subject serum was also used to treat activated THP-1 cells to determine relative quantities of 3 inflammatory cytokine (tumor necrosis factor-α [TNF-α], interleukin-1α [IL-1α], and IL-6) mRNAs. RESULTS: Herbs and spices that protected PBMCs against DNA strand breaks were paprika, rosemary, ginger, heat-treated turmeric, sage, and cumin. Paprika also appeared to protect cells from normal apoptotic processes. Of the 3 cytokine mRNAs studied (TNF-α, IL-1α, and IL-6), TNF-α was the most sensitive responder to oxidized LDL-treated macrophages. Clove, ginger, rosemary, and turmeric were able to significantly reduce oxidized LDL-induced expression of TNF-α. Serum from those consuming ginger reduced all three inflammatory biomarkers. Ginger, rosemary, and turmeric showed protective capacity by both oxidative protection and inflammation measures. CONCLUSIONS: DNA strand breaks and inflammatory biomarkers are a good functional measure of a food's bioavailability.",
"title": "Bioavailability of herbs and spices in humans as determined by ex vivo inflammatory suppression and DNA strand breaks."
},
{
"docid": "MED-2209",
"text": "This study investigated the effect of different traditional cooking methods on glycemic index (GI) and glycemic response of ten Sweet potato (Ipomoea batatas) cultivars commonly eaten in Jamaica. Matured tubers were cooked by roasting, baking, frying, or boiling then immediately consumed by the ten nondiabetic test subjects (5 males and 5 females; mean age of 27 ± 2 years). The GI varied between 41 ± 5–93 ± 5 for the tubers studied. Samples prepared by boiling had the lowest GI (41 ± 5–50 ± 3), while those processed by baking (82 ± 3–94 ± 3) and roasting (79 ± 4–93 ± 2) had the highest GI values. The study indicates that the glycemic index of Jamaican sweet potatoes varies significantly with the method of preparation and to a lesser extent on intravarietal differences. Consumption of boiled sweet potatoes could minimize postprandial blood glucose spikes and therefore, may prove to be more efficacious in the management of type 2 diabetes mellitus.",
"title": "Relationship between Processing Method and the Glycemic Indices of Ten Sweet Potato (Ipomoea batatas) Cultivars Commonly Consumed in Jamaica"
},
{
"docid": "MED-3242",
"text": "Previous studies have suggested that dietary factors may be important in the development of bladder cancer. We examined macronutrient intake in relation to risk of urothelial cell carcinoma among 469,339 men and women in the European Prospective Investigation into Cancer and Nutrition. Associations were examined using Cox regression, stratified by sex, age at recruitment and centre and further adjusted for smoking status and duration, body mass index and total energy intake. After an average of 11.3 years of follow-up, 1,416 new cases of urothelial cell carcinoma were identified. After allowing for measurement error, a 3% increase in the consumption of energy intake from animal protein was associated with a 15% higher risk (95% confidence interval [CI]: 3-30%; p(trend) = 0.01) and a 2% increase in energy from plant protein intake was associated with a 23% lower risk (95% CI: 36-7%, p(trend) = 0.006). Dietary intake of fat, carbohydrate, fibre or calcium was not associated with risk. These findings suggest that animal and/or plant protein may affect the risk of urothelial cell carcinoma, and examination of these associations in other studies is needed. Copyright © 2012 UICC.",
"title": "Macronutrient intake and risk of urothelial cell carcinoma in the European prospective investigation into cancer and nutrition."
},
{
"docid": "MED-4258",
"text": "The objective of the present study was to assess animal and plant protein intakes in the Belgian population and to examine their relationship with overweight and obesity (OB). The subjects participated in the Belgian National Food Consumption Survey conducted in 2004. Food consumption was assessed by using two non-consecutive 24 h dietary recalls. About 3083 participants ( ≥ 15 years of age; 1546 males, 1537 females) provided completed dietary information. Animal protein intake (47 g/d) contributed more to total protein intakes of 72 g/d than plant protein intake, which accounted for 25 g/d. Meat and meat products were the main contributors to total animal protein intakes (53 %), whereas cereals and cereal products contributed most to plant protein intake (54 %). Males had higher animal and plant protein intakes than females (P < 0·001). Legume and soya protein intakes were low in the whole population (0·101 and 0·174 g/d, respectively). In males, animal protein intake was positively associated with BMI (β = 0·013; P = 0·001) and waist circumference (WC; β = 0·041; P = 0·002). Both in males and females, plant protein intake was inversely associated with BMI (males: β = - 0·036; P < 0·001; females: β = - 0·046; P = 0·001) and WC (male: β = - 0·137; P < 0·001; female: β = - 0·096; P = 0·024). In conclusion, plant protein intakes were lower than animal protein intakes among a representative sample of the Belgian population and decreased with age. Associations with anthropometric data indicated that plant proteins could offer a protective effect in the prevention of overweight and OB in the Belgian population.",
"title": "Plant and animal protein intake and its association with overweight and obesity among the Belgian population."
},
{
"docid": "MED-3455",
"text": "Exercise-induced deoxyribonucleic acid (DNA) damage is often associated with an increase in free radicals; however, there is a lack of evidence examining the two in parallel. This study tested the hypothesis that high-intensity exercise has the ability to produce free radicals that may be capable of causing DNA damage. Twelve apparently healthy male subjects (age: 23 ± 4 years; stature: 181 ± 8 cm; body mass: 80 ± 9 kg; and VO(2max) : 49 ± 5 ml/kg/min) performed three 5 min consecutive and incremental stages (40, 70, and 100% of VO(2max) ) of aerobic exercise with a 15-min period separating each stage. Blood was drawn after each bout of exercise for the determination of ex vivo free radicals, DNA damage, protein carbonyls, lipid hydroperoxide (LOOH) concentration, and a range of lipid-soluble antioxidants. Lipid-derived oxygen-centered free radicals (hyperfine coupling constants a(Nitrogen) = 13.7 Gauss (G) and aβ(Hydrogen) = 1.8 G) increased as a result of acute moderate and high-intensity exercise (P < 0.05), while DNA damage was also increased (P < 0.05). Systemic changes were observed in LOOH and for lipid-soluble antioxidants throughout exercise (P < 0.05); however, there was no observed change in protein carbonyl concentration (P > 0.05). These findings identify lipid-derived free radical species as possible contributors to peripheral mononuclear cell DNA damage in the human exercising model. This damage occurs in the presence of lipid oxidation but in the absence of any change to protein carbonyl concentration. The significance of these findings may have relevance in terms of immune function, the aging process, and the pathology of carcinogenesis. Copyright © 2010 Wiley-Liss, Inc.",
"title": "Exercise-induced lipid peroxidation: Implications for deoxyribonucleic acid damage and systemic free radical generation."
},
{
"docid": "MED-4049",
"text": "More than 85% of breast cancers are sporadic and attributable to long-term exposure to environmental carcinogens, such as those in the diet, through a multistep disease process progressing from non-cancerous to premalignant and malignant stages. The chemical carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is one of the most abundant heterocyclic amines found in high-temperature cooked meats and is recognized as a mammary carcinogen. However, the PhIP’s mechanism of action in breast cell carcinogenesis is not clear. Here, we demonstrated, for the first time, that cumulative exposures to PhIP at physiologically achievable, pico to nanomolar concentrations effectively induced progressive carcinogenesis of human breast epithelial MCF10A cells from a non-cancerous stage to premalignant and malignant stages in a dose- and exposure-dependent manner. Progressive carcinogenesis was measured by increasingly- acquired cancer-associated properties of reduced dependence on growth factors, anchorage-independent growth, acinar-conformational disruption, proliferation, migration, invasion, tumorigenicity with metastasis and increased stem-like cell populations. These biological changes were accompanied by biochemical and molecular changes, including upregulated H-Ras gene expression, extracellular signal-regulated kinase (ERK) pathway activation, Nox-1 expression, reactive oxygen species (ROS) elevation, increased HIF-1α, Sp1, tumor necrosis factor-α, matrix metalloproteinase (MMP)-2, MMP-9, aldehyde dehydrogenase activity and reduced E-cadherin. The Ras-ERK-Nox-ROS pathway played an important role in not only initiation but also maintenance of cellular carcinogenesis induced by PhIP. Using biological, biochemical and molecular changes as targeted endpoints, we identified that the green tea catechin components epicatechin-3-gallate and epigallocatechin-3-gallate, at non-cytotoxic doses, were capable of suppressing PhIP-induced cellular carcinogenesis and tumorigenicity.",
"title": "Intervention of human breast cell carcinogenesis chronically induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine"
},
{
"docid": "MED-3273",
"text": "Recent studies confirm that dietary methionine restriction increases both mean and maximal lifespan in rats and mice, achieving \"aging retardant\" effects very similar to those of caloric restriction, including a suppression of mitochondrial superoxide generation. Although voluntary caloric restriction is never likely to gain much popularity as a pro-longevity strategy for humans, it may be more feasible to achieve moderate methionine restriction, in light of the fact that vegan diets tend to be relatively low in this amino acid. Plant proteins - especially those derived from legumes or nuts - tend to be lower in methionine than animal proteins. Furthermore, the total protein content of vegan diets, as a function of calorie content, tends to be lower than that of omnivore diets, and plant protein has somewhat lower bioavailability than animal protein. Whole-food vegan diets that moderate bean and soy intake, while including ample amounts of fruit and wine or beer, can be quite low in methionine, while supplying abundant nutrition for health (assuming concurrent B12 supplementation). Furthermore, low-fat vegan diets, coupled with exercise training, can be expected to promote longevity by decreasing systemic levels of insulin and free IGF-I; the latter effect would be amplified by methionine restriction - though it is not clear whether IGF-I down-regulation is the sole basis for the impact of low-methionine diets on longevity in rodents.",
"title": "The low-methionine content of vegan diets may make methionine restriction feasible as a life extension strategy."
},
{
"docid": "MED-3359",
"text": "Background Fruit and vegetable consumption and ingestion of carotenoids have been found to be associated with human skin-color (yellowness) in a recent cross-sectional study. This carotenoid-based coloration contributes beneficially to the appearance of health in humans and is held to be a sexually selected cue of condition in other species. Methodology and Principal Findings Here we investigate the effects of fruit and vegetable consumption on skin-color longitudinally to determine the magnitude and duration of diet change required to change skin-color perceptibly. Diet and skin-color were recorded at baseline and after three and six weeks, in a group of 35 individuals who were without makeup, self-tanning agents and/or recent intensive UV exposure. Six-week changes in fruit and vegetable consumption were significantly correlated with changes in skin redness and yellowness over this period, and diet-linked skin reflectance changes were significantly associated with the spectral absorption of carotenoids and not melanin. We also used psychophysical methods to investigate the minimum color change required to confer perceptibly healthier and more attractive skin-coloration. Modest dietary changes are required to enhance apparent health (2.91 portions per day) and attractiveness (3.30 portions). Conclusions Increased fruit and vegetable consumption confers measurable and perceptibly beneficial effects on Caucasian skin appearance within six weeks. This effect could potentially be used as a motivational tool in dietary intervention.",
"title": "You Are What You Eat: Within-Subject Increases in Fruit and Vegetable Consumption Confer Beneficial Skin-Color Changes"
},
{
"docid": "MED-2656",
"text": "The aim of previous research into the causes of allergic diseases, including asthma was mostly to identify potential risk factors in the environment. No major risk factors have been identified, however. Over the past 10 years, focus has, therefore, more been directed towards protective factors that could enhance the development of tolerance to allergens which were previously encountered early in life, but are now lost in modern affluent societies. In particular, the role of childhood infections has been discussed, but so far these studies have not been conclusive. Recent epidemiological studies and experimental research suggest that the microbial environment and exposure to microbial products in infancy modifies immune responses and enhances the development of tolerance to ubiquitous allergens. The intestinal microflora may play a particular role in this respect, as it is the major external driving force in the maturation of the immune system after birth, and animal experiments have shown it to be a prerequisite for normal development of oral tolerance. Recent studies have shown differences in the composition of the microflora between healthy and allergic infants in countries with a high and low prevalence of allergies and between healthy and allergic infants within such countries. These differences are apparent within the first week of life and thus precede clinical symptoms. The use of live microorganisms that might be beneficial to health has a long tradition and the safety is well documented. Very recently, several prospective intervention studies, modifying the gut flora from birth have yielded encouraging results and may suggest a new mode of primary prevention of allergy in the future.",
"title": "Effects of intestinal microflora and the environment on the development of asthma and allergy."
},
{
"docid": "MED-3535",
"text": "Cherries, and in particular sweet cherries, are a nutritionally dense food rich in anthocyanins, quercetin, hydroxycinnamates, potassium, fiber, vitamin C, carotenoids, and melatonin. UV concentration, degree of ripeness, postharvest storage conditions, and processing, each can significantly alter the amounts of nutrients and bioactive components. These constituent nutrients and bioactive food components support the potential preventive health benefits of cherry intake in relation to cancer, cardiovascular disease, diabetes, inflammatory diseases, and Alzheimer's disease. Mechanistically, cherries exhibit relatively high antioxidant activity, low glycemic response, COX 1 and 2 enzyme inhibition, and other anti-carcinogenic effects in vitro and in animal experiments. Well-designed cherry feeding studies are needed to further substantiate any health benefits in humans.",
"title": "Cherries and health: a review."
},
{
"docid": "MED-3876",
"text": "BACKGROUND: Chinese men have lower incidences of prostate cancer compared to men from Europe and North America. Asians consume large quantities of soya, a rich source of isoflavanoids phyto-oestrogens and have high plasma and urinary levels of these compounds. The mammalian lignans, enterolactone and enterodiol, are another group of weak plant oestrogens and are derived from seeds, cereals and grains. Vegetarians have high plasma and urinary concentrations of lignans. METHODS: The concentrations lignans and isoflavonic phyto-oestrogens were determined by gas chromatography-mass spectrometry (GC-MS) in plasma and prostatic fluid from Portuguese, Chinese and British men consuming their traditional diets. RESULTS: In prostatic fluid the mean concentrations of enterolactone were 31, 162 and 20.3 ng/ml for Hong Kong, Portugal and Britain respectively. Very high levels of enterolactone (> 600 ng/ml) were observed in the prostatic fluid of some of the men from Portugal. High concentrations of equol (3270 ng/ml) and daidzein (532 ng/ml) were found in a sample of prostatic fluid from Hong Kong. Higher mean levels of daidzein were observed in prostatic fluid from Hong Kong at 70 ng/ml, compared to 4.6 and 11.3 ng/ml in samples from Portugal and Britain respectively. Mean levels of daidzein were higher in the plasma samples from Hong Kong (31.3 ng/ml) compared to those from Portugal (1.3 ng/ml) and Britain (8.2 ng/ml). In general, the mean plasma concentrations of enterolactone from the three centres were similar, at 6.2, 3.9 and 3.9 ng/ml in samples from Hong Kong Portugal and Britain respectively. CONCLUSIONS: Higher concentrations of the isoflavanoid phyto-oestrogens, daidzein and equol, were found in the plasma and prostatic fluid of men from Hong Kong compared to those from Britain and Portugal. However, the levels of the lignan, enterolactone, were very much higher in prostatic fluid of Portuguese men. Isoflavanoids and lignans have many interesting properties and may, in part, be responsible for lower incidences of prostate cancer in men from Asia and also some Mediterranean countries. The isoflavanoids from soya, which are present in high concentrations in the prostatic fluid of Asian men, may be protective against prostate disease.",
"title": "Lignans and isoflavonoids in plasma and prostatic fluid in men: samples from Portugal, Hong Kong, and the United Kingdom."
},
{
"docid": "MED-2513",
"text": "Over the last several years, new evidence has kept pouring in about the remarkable effect of caloric restriction (CR) on the conspicuous bedfellows- aging and cancer. Through the use of various animal models, it is now well established that by reducing calorie intake one can not only increase life span but, also, lower the risk of various age related diseases such as cancer. Cancer cells are believed to be more dependent on glycolysis for their energy requirements than normal cells and, therefore, can be easily targeted by alteration in the energy-metabolic pathways, a hallmark of CR. Apart from inhibiting the growth of transplantable tumors, CR has been also shown to inhibit the development of spontaneous, radiation, and chemically induced tumors. The question regarding the potentiality of the anti-tumor effect of CR in humans has been in part answered by the resistance of a cohort of women, who had suffered from anorexia in their early life, to breast cancer. However, human research on the beneficial effect of CR is still at an early stage and needs further validation. Though the complete mechanism of the anti-tumor effect of CR is far from clear, the plausible involvement of nutrient sensing pathways or IGF-1 pathways proposed for its anti-aging action cannot be overruled. In fact, cancer cell lines, mutant for proteins involved in IGF-1 pathways, failed to respond to CR. In addition, CR decreases the levels of many growth factors, anabolic hormones, inflammatory cytokines, and oxidative markers that are deregulated in several cancers. In this review, we discuss the anti-tumor effect of CR, describing experiments done in vitro in tumor models and in vivo in mouse models in which the tumor was induced by means of radiation or chemical exposure, expressing oncogenes or deleting tumor suppression genes. We also discuss the proposed mechanisms of CR anti-tumor action. Lastly, we argue the necessity of gene expression studies in cancerous versus normal cells upon CR.",
"title": "Insights into the beneficial effect of caloric/ dietary restriction for a healthy and prolonged life"
},
{
"docid": "MED-3141",
"text": "OBJECTIVE: To evaluate the associations with chronic disease risk and mortality of the consequences of bean-free diets in Taiwanese adults with regard to gender. DESIGN: A sub-sample of the National Health Interview Survey (NHIS) in 2001 agreed to physical examination in the subsequent year. This group then took part in the Taiwanese Survey of Hyperglycaemia, Hyperlipidaemia and Hypertension (TwSHHH) in 2002. SETTING: Individual records were linked to the eventual death files from 2002 to 2008. SUBJECTS: Up to the end of 2008, a total of 2820 men and 2950 women were tracked by death registry over the 6·8 years of follow-up. RESULTS: Among 38,077 person-years, an average follow-up 6·5 years, 225 all-cause deaths were identified. Generalized linear models showed beans to be favourable for metabolic syndrome (other than for fasting glucose) in men; in women, beans were favourable for waist circumference and HbA1c. Cumulative logistic regression models for the effect of a bean-free diet on metabolic syndrome scores according to the Taiwanese-modified National Cholesterol Education Program-Adult Treatment Panel III (NCEP-tw) gave adjusted odds ratios of 1·83 in men and 1·45 in women. Cox regression models for the bean-free diet showed an increased hazard ratio for all-cause mortality among women (1·98, 95% CI 1·03, 3·81) but not men (1·28, 95% CI 0·76, 2·16). CONCLUSIONS: A bean-free diet may play a role in developing the metabolic syndrome in both genders, and is a significant predictor of all-cause mortality in Taiwanese women but not men.",
"title": "A bean-free diet increases the risk of all-cause mortality among Taiwanese women: the role of the metabolic syndrome."
},
{
"docid": "MED-3281",
"text": "INTRODUCTION: Amino acid auxotrophy or the metabolic defect which renders cancer incapable of surviving under amino acid depleted conditions is being exploited and explored as a therapeutic against cancer. Early clinical data on asparagine- and arginine-depleting drugs have demonstrated low toxicity and efficacy in melanoma, hepatocellular carcinoma and acute lymphoblastic leukemia. Methionine auxotrophy is a novel niche currently under exploration for targeting certain cancers. AREAS COVERED: In this review we explore the discovery of methionine auxotrophy followed by in vitro, in vivo and patient data on targeting cancer with methionine depletion. We end with a small discussion on bioengineering, pegylation and red blood cell encapsulation as mechanisms for decreasing immunogenicity of methionine-depleting drugs. We hope to provide a platform for future pharmacology, toxicology and cytotoxicity studies with methionine depletion therapy and drugs. EXPERT OPINION: Although methionine auxotrophy seems as a viable target, extensive research addressing normal versus cancer cell toxicity needs to be conducted. Further research also needs to be conducted into the molecular mechanism associated with methionine depletion therapy. Finally, novel methods need to be developed to decrease the immunogenicity of methionine-depleting drugs, a current issue with protein therapeutics.",
"title": "Targeting methionine auxotrophy in cancer: discovery & exploration."
},
{
"docid": "MED-3874",
"text": "Background Prostate cancer affects one-out-of-six men during their lifetime. Dietary factors are postulated to influence the development and progression of prostate cancer. Low-fat diets and flaxseed supplementation may offer potentially protective strategies. Methods We undertook a multi-site, randomized controlled trial to test the effects of low-fat and/or flaxseed-supplemented diets on the biology of the prostate and other biomarkers. Prostate cancer patients (n=161) scheduled at least 21 days before prostatectomy were randomly assigned to one of the following arms: 1) control (usual diet); 2) flaxseed-supplemented diet (30 g/day); 2) low-fat diet (<20% total energy); or 4) flaxseed-supplemented, low-fat diet. Blood was drawn at baseline and prior to surgery and analyzed for prostate specific antigen (PSA), sex hormone binding globulin, testosterone, insulin-like growth factor-1 and binding protein-3, c-reactive protein, and total and low density lipoprotein cholesterol. Tumors were assessed for proliferation (Ki-67, the primary endpoint) and apoptosis. Results Men were on protocol an average of 30 days. Proliferation rates were significantly lower (P < 0.002) among men assigned to the flaxseed arms. Median Ki-67 positive cells/total nuclei ratios (x100) were 1.66 (flaxseed-supplemented diet) and 1.50 (flaxseed-supplemented, low-fat diet) vs. 3.23 (control) and 2.56 (low-fat diet). No differences were observed between arms with regard to side effects, apoptosis, and most serological endpoints; however, men on low-fat diets experienced significant decreases in serum cholesterol (P=0.048). Conclusions Findings suggest that flaxseed is safe, and associated with biologic alterations that may be protective for prostate cancer. Data also further support low-fat diets to manage serum cholesterol.",
"title": "Flaxseed Supplementation (not Dietary Fat Restriction) Reduces Prostate Cancer Proliferation Rates in Men Presurgery"
},
{
"docid": "MED-4050",
"text": "Green tea is a commonly consumed beverage in Asia and has been suggested to have anti-inflammatory and possible anti-carcinogenic properties in laboratory studies. We sought to examine the association between green tea consumption and risk of breast cancer incidence or recurrence, using all available epidemiologic evidence to date. We conducted a systematic search of five databases and performed a meta-analysis of studies of breast cancer risk and recurrence published between 1998 and 2009, encompassing 5,617 cases of breast cancer. Summary relative risks (RR) were calculated using a fixed effects model, and tests of heterogeneity across combined studies were conducted. We identified two studies of breast cancer recurrence and seven studies of breast cancer incidence. Increased green tea consumption (more than three cups a day) was inversely associated with breast cancer recurrence (Pooled RR = 0.73, 95% CI: 0.56-0.96). An analysis of case-control studies of breast cancer incidence suggested an inverse association with a pooled RR of 0.81 (95% CI: 0.75, 0.88) while no association was found among cohort studies of breast cancer incidence. Combining all studies of breast cancer incidence resulted in significant heterogeneity. Available epidemiologic evidence supports the hypothesis that increased green tea consumption may be inversely associated with risk of breast cancer recurrence. The association between green tea consumption and breast cancer incidence remains unclear based on the current evidence.",
"title": "Green tea consumption and breast cancer risk or recurrence: a meta-analysis."
},
{
"docid": "MED-3197",
"text": "Background: A Step I diet with lean beef compared with lean white meat both decrease LDL cholesterol. To our knowledge, no studies have evaluated a low–saturated fatty acid (SFA) (<7% calories) diet that contains lean beef. Objective: We studied the effect on LDL cholesterol of cholesterol-lowering diets with varying amounts of lean beef [ie, Dietary Approaches to Stop Hypertension (DASH): 28 g beef/d; Beef in an Optimal Lean Diet (BOLD): 113 g beef/d; and Beef in an Optimal Lean Diet plus additional protein (BOLD+): 153 g beef/d] compared with that of a healthy American diet (HAD). Design: Thirty-six hypercholesterolemic participants (with LDL-cholesterol concentrations >2.8 mmol/L) were randomly assigned to consume each of the 4 diets (HAD: 33% total fat, 12% SFA, 17% protein, and 20 g beef/d), DASH (27% total fat, 6% SFA, 18% protein, and 28 g beef/d), BOLD (28% total fat, 6% SFA, 19% protein, and 113 g beef/d), and BOLD+ (28% total fat, 6% SFA, 27% protein, and 153 g beef/d) for 5 wk. Results: There was a decrease in total cholesterol (TC) and LDL-cholesterol concentrations (P < 0.05) after consumption of the DASH (−0.49 ± 0.11 and −0.37 ± 0.09 mmol/L, respectively), BOLD (−0.48 ± 0.10 and −0.35 ± 0.9 mmol/L, respectively), and BOLD+ (−0.50 ± 0.10 and −0.345 ± 0.09 mmol/L, respectively) diets compared with after consumption of the HAD (−0.22 ± 0.10 and −0.14 ± 0.10 mmol/L, respectively). Apolipoprotein A-I, C-III, and C-III bound to apolipoprotein A1 particles decreased after BOLD and BOLD+ diets compared with after the HAD, and there was a greater decrease in apolipoprotein B after consumption of the BOLD+ diet than after consumption of the HAD (P < 0.05 for both). LDL cholesterol and TC decreased after consumption of the DASH, BOLD, and BOLD+ diets when the baseline C-reactive protein (CRP) concentration was <1 mg/L; LDL cholesterol and TC decreased when baseline CRP concentration was >1 mg/L with the BOLD and BOLD+ diets. Conclusions: Low-SFA, heart-healthy dietary patterns that contain lean beef elicit favorable effects on cardiovascular disease (CVD) lipid and lipoprotein risk factors that are comparable to those elicited by a DASH dietary pattern. These results, in conjunction with the beneficial effects on apolipoprotein CVD risk factors after consumption of the BOLD and BOLD+ diets, which were greater with the BOLD+ diet, provide support for including lean beef in a heart-healthy dietary pattern. This trial was registered at clinicaltrials.gov as NCT00937898.",
"title": "Beef in an Optimal Lean Diet study: effects on lipids, lipoproteins, and apolipoproteins"
},
{
"docid": "MED-1721",
"text": "Objective To examine the relation between body mass index (kg/m2) and cancer incidence and mortality. Design Prospective cohort study. Participants 1.2 million UK women recruited into the Million Women Study, aged 50-64 during 1996-2001, and followed up, on average, for 5.4 years for cancer incidence and 7.0 years for cancer mortality. Main outcome measures Relative risks of incidence and mortality for all cancers, and for 17 specific types of cancer, according to body mass index, adjusted for age, geographical region, socioeconomic status, age at first birth, parity, smoking status, alcohol intake, physical activity, years since menopause, and use of hormone replacement therapy. Results 45 037 incident cancers and 17 203 deaths from cancer occurred over the follow-up period. Increasing body mass index was associated with an increased incidence of endometrial cancer (trend in relative risk per 10 units=2.89, 95% confidence interval 2.62 to 3.18), adenocarcinoma of the oesophagus (2.38, 1.59 to 3.56), kidney cancer (1.53, 1.27 to 1.84), leukaemia (1.50, 1.23 to 1.83), multiple myeloma (1.31, 1.04 to 1.65), pancreatic cancer (1.24, 1.03 to 1.48), non-Hodgkin's lymphoma (1.17, 1.03 to 1.34), ovarian cancer (1.14, 1.03 to 1.27), all cancers combined (1.12, 1.09 to 1.14), breast cancer in postmenopausal women (1.40, 1.31 to 1.49) and colorectal cancer in premenopausal women (1.61, 1.05 to 2.48). In general, the relation between body mass index and mortality was similar to that for incidence. For colorectal cancer, malignant melanoma, breast cancer, and endometrial cancer, the effect of body mass index on risk differed significantly according to menopausal status. Conclusions Increasing body mass index is associated with a significant increase in the risk of cancer for 10 out of 17 specific types examined. Among postmenopausal women in the UK, 5% of all cancers (about 6000 annually) are attributable to being overweight or obese. For endometrial cancer and adenocarcinoma of the oesophagus, body mass index represents a major modifiable risk factor; about half of all cases in postmenopausal women are attributable to overweight or obesity.",
"title": "Cancer incidence and mortality in relation to body mass index in the Million Women Study: cohort study"
},
{
"docid": "MED-1724",
"text": "A considerable amount of evidence is consistent with the proposition that systemic IGF-I activity acts as pacesetter in the aging process. A reduction in IGF-I activity is the common characteristic of rodents whose maximal lifespan has been increased by a wide range of genetic or dietary measures, including caloric restriction. The lifespans of breeds of dogs and strains of rats tend to be inversely proportional to their mature weight and IGF-I levels. The link between IGF-I and aging appears to be evolutionarily conserved; in worms and flies, lifespan is increased by reduction-of-function mutations in signaling intermediates homologous to those which mediate insulin/IGF-I activity in mammals. The fact that an increase in IGF-I activity plays a key role in the induction of sexual maturity, is consistent with a broader role for-IGF-I in aging regulation. If down-regulation of IGF-I activity could indeed slow aging in humans, a range of practical measures for achieving this may be at hand. These include a low-fat, whole-food, vegan diet, exercise training, soluble fiber, insulin sensitizers, appetite suppressants, and agents such as flax lignans, oral estrogen, or tamoxifen that decrease hepatic synthesis of IGF-I. Many of these measures would also be expected to decrease risk for common age-related diseases. Regimens combining several of these approaches might have a sufficient impact on IGF-I activity to achieve a useful retardation of the aging process. However, in light of the fact that IGF-I promotes endothelial production of nitric oxide and may be of especial importance to cerebrovascular health, additional measures for stroke prevention-most notably salt restriction-may be advisable when attempting to down-regulate IGF-I activity as a pro-longevity strategy.",
"title": "A low-fat, whole-food vegan diet, as well as other strategies that down-regulate IGF-I activity, may slow the human aging process."
},
{
"docid": "MED-1711",
"text": "Summary Objectives The insulin-like growth factor (IGF) signaling pathway has been implicated in the pathogenesis of numerous tumor types, including non-small cell lung cancer (NSCLC). Figitumumab is a fully human IgG2 monoclonal antibody against IGF-1 receptor (IGF-1R). Methods This phase I, open-label, dose-escalation study (ClinicalTrials.gov: NCT00603538) assessed the safety and tolerability of figitumumab (6, 10 and 20 mg/kg) in combination with carboplatin (area under the curve: 6 mg·min/mL) and paclitaxel (200 mg/m2) in Japanese patients (N = 19) with chemotherapy-naïve, advanced NSCLC. Treatments were administered intravenously on day 1 of a 21-day cycle for four to six cycles. Pharmacokinetics, biomarkers, and antitumor activity were also evaluated. Results Figitumumab in combination with carboplatin and paclitaxel was well tolerated at doses up to 20 mg/kg; no dose-limiting toxicities were observed at this dose level. When given in combination, figitumumab plasma exposure increased in an approximately dose-proportional manner. The approximate 2-fold accumulation following repeated administration supported the 21-day regimen as appropriate for figitumumab administration. Serum total IGF-1 and IGF binding protein-3 concentrations increased following figitumumab dosing, but a clear dose-dependent relationship was not demonstrated. Seven of 18 evaluable patients experienced a partial response. Conclusions Figitumumab 20 mg/kg in combination with carboplatin and paclitaxel was well tolerated in chemotherapy-naïve Japanese patients with NSCLC. Further analysis of biomarker data is necessary for the development of figitumumab therapy.",
"title": "Figitumumab combined with carboplatin and paclitaxel in treatment-naïve Japanese patients with advanced non-small cell lung cancer"
},
{
"docid": "MED-1258",
"text": "Reductions in low-density lipoprotein-cholesterol (LDL-C) result from diets containing almonds, or diets that are either low in saturated fat or high in viscous fibers, soy proteins, or plant sterols. We have therefore combined all of these interventions in a single diet (portfolio diet) to determine whether cholesterol reductions could be achieved of similar magnitude to those reported in recent statin trials which reduced cardiovascular events. Twenty-five hyperlipidemic subjects consumed either a portfolio diet (n=13), very low in saturated fat and high in plant sterols (1.2 g/1,000 kcal), soy protein (16.2 g/1,000 kcal), viscous fibers (8.3 g/1,000 kcal), and almonds (16.6 g/1,000 kcal), or a low-saturated fat diet (n=12) based on whole-wheat cereals and low-fat dairy foods. Fasting blood, blood pressure, and body weight were obtained at weeks 0, 2, and 4 of each phase. LDL-C was reduced by 12.1% +/- 2.4% (P<.001) on the low-fat diet and by 35.0% +/- 3.1% (P<.001) on the portfolio diet, which also reduced the ratio of LDL-C to high-density lipoprotein-cholesterol (HDL-C) significantly (30.0% +/- 3.5%; P<.001). The reductions in LDL-C and the LDL:HDL-C ratio were both significantly lower on the portfolio diet than on the control diet (P<.001 and P<.001, respectively). Mean weight loss was similar on test and control diets (1.0 kg and 0.9 kg, respectively). No difference was seen in blood pressure, HDL-C, serum triglycerides, lipoprotein(a) [Lp(a)], or homocysteine concentrations between diets. Combining a number of foods and food components in a single dietary portfolio may lower LDL-C similarly to statins and so increase the potential effectiveness of dietary therapy.",
"title": "The effect of combining plant sterols, soy protein, viscous fibers, and almonds in treating hypercholesterolemia."
},
{
"docid": "MED-3775",
"text": "We investigated the beneficial effects of drinking supplementary water during the school day on the cognitive performance and transitory subjective states, such as fatigue or vigor, in 168 children aged between 9 and 11years who were living in a hot climate (South Italy, Sardinia). The classes were randomly divided into an intervention group, which received water supplementation, and a control group. Dehydration was determined by urine sampling and was defined as urine osmolality greater than 800mOsm/kg H(2)O (Katz, Massry, Agomn, & Toor, 1965). The change in the scores from the morning to the afternoon of hydration levels, cognitive performance and transitory subjective states were correlated. In line with a previous observational study that evaluated the hydration status of school children living in a country with a hot climate (Bar-David, Urkin, & Kozminsky, 2005), our results showed that a remarkable proportion of children were in a state of mild, voluntary dehydration at the beginning of the school day (84%). We found a significant negative correlation between dehydration and the auditory number span, which indicates a beneficial effect of drinking supplementary water at school on short-term memory. Moreover, there was a positive correlation between dehydration and performance in the verbal analogy task. The results are discussed in the light of the complexity of the neurobiological mechanisms involved in the relationship between hydration status and cognition. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Effects of drinking supplementary water at school on cognitive performance in children."
},
{
"docid": "MED-2445",
"text": "Allergic disorders encompass skin, food and respiratory allergies. Sensitization to a normally harmless allergen results in the immune system being biased to a predominant T-helper type 2 response. Re-exposure to the same allergen leads to a robust secretion of allergy-related mediators that eventually triggers symptoms. Our understanding of these disorders has enabled the search of therapeutic approaches that can either modulate the sensitization process or impact on allergic mediators, thus helping manage allergic symptoms. Polyphenols are one such class of compounds that are found in foods and plant sources and have been investigated for their anti-allergic effect in different disease models and in human clinical trials. Their anti-inflammatory profile is known to impact on the recruitment of immune cells to the skin and in preventing the development of secondary infections following disruption of the skin barrier. The interaction of polyphenols with proteins can modulate the process of allergic sensitization and their direct effect on allergic effector cells such as mast cells inhibit mediator release, resulting in the alleviation of symptoms. In addition, their endogenous anti-oxidant ability limits the extent of cellular injury from free radicals during the allergic insult. Overall, polyphenols hold promise as anti-allergy agents capable of influencing multiple biological pathways and immune cell functions in the allergic immune response and deserve further investigation. The objective of the current review is to summarize the key findings and progress made in studying polyphenols as anti-allergic ingredients. Special emphasis is placed in this review to highlight key physiological, cellular and signalling pathways implicated in the mechanism of action of different polyphenols in the context of allergic disorders and their manifestations. © 2011 Blackwell Publishing Ltd.",
"title": "Dietary polyphenols in the prevention and treatment of allergic diseases."
},
{
"docid": "MED-3278",
"text": "Lung cancer (LC) continues to represent a heavy burden for health care systems worldwide. Epidemiological studies predict that its role will increase in the near future. While patient prognosis is strongly associated with tumour stage and early detection of disease, no screening test exists so far. It has been suggested that electronic sensor devices, commonly referred to as ‘electronic noses’, may be applicable to identify cancer-specific volatile organic compounds in the breath of patients and therefore may represent promising screening technologies. However, three decades of research did not bring forward a clinically applicable device. Here, we propose a new research approach by involving specially trained sniffer dogs into research strategies by making use of their ability to identify LC in the breath sample of patients.",
"title": "Sniffer dogs as part of a bimodal bionic research approach to develop a lung cancer screening"
},
{
"docid": "MED-3958",
"text": "Flanders is densely populated with much industry and intensive farming. Sexual maturation of adolescents (aged 14-15 years) was studied in relation to internal exposure to pollutants. Serum levels of pollutants and sex hormones were measured in 1679 participants selected as a random sample of the adolescents residing in the study areas. Data on sexual development were obtained from the medical school examination files. Self-assessment questionnaires provided information on health, use of medication and lifestyle factors. In boys, serum levels of hexachlorobenzene (HCB), p,p'-DDE and polychlorinated biphenyls (sum of marker PCB138, 153 and 180) were significantly and positively associated with pubertal staging (pubic hair and genital development). Higher levels of serum HCB and blood lead were associated with, respectively, a lower and a higher risk of gynecomastia. In girls, significant and negative associations were detected between blood lead and pubic hair development; higher exposure to PCBs was significantly associated with a delay in timing of menarche. Environmental exposures to pollutants at levels actually present in the Flemish population are associated with measurable effects on pubertal development. However, further understanding of toxic mode of action and sensitive windows of exposure is needed to explain the current findings.",
"title": "Internal exposure to pollutants and sexual maturation in Flemish adolescents."
},
{
"docid": "MED-3451",
"text": "Oxidative stress is a natural physiological process that describes an imbalance between free radical production and the ability of the antioxidant defence system of the body to neutralize free radicals. Free radicals can be beneficial as they may promote wound healing and contribute to a healthy immune response. However, free radicals can have a detrimental impact when they interfere with the regulation of apoptosis and thus play a role in the promotion of some cancers and conditions such as cardiovascular disease. Antioxidants are molecules that reduce the damage associated with oxidative stress by counteracting free radicals. Regular exercise is a vital component of a healthy lifestyle, although it can increase oxidative stress. As a typical vegetarian diet comprises a wide range of antioxidant-rich foods, it is plausible that the consumption of these foods will result in an enhanced antioxidant system capable of reducing exercise-induced oxidative stress. In addition, a relationship between a vegetarian diet and lower risks of cardiovascular disease and some cancers has been established. This review explores the current available evidence linking exercise, vegetarians, antioxidants, and oxidative stress.",
"title": "Could a vegetarian diet reduce exercise-induced oxidative stress? A review of the literature."
},
{
"docid": "MED-3954",
"text": "BACKGROUND: A male epidemic of ischaemic heart disease (IHD) emerges with economic development. It has previously been hypothesised that this epidemic is due to nutritionally driven levels of pubertal sex steroids, which lead to a more atherogenic body shape and lipid profile in boys but not girls, without any sex-specific effects on glucose metabolism. This study tests this hypothesis by examining the association of childhood meat eating with IHD risk in a developing Chinese population. METHODS: Multivariable linear and censored regression was used in a cross-sectional study of 19,418 Chinese older (≥ 50 years) men and women from the Guangzhou Biobank Cohort Study (phases 2 and 3) to assess the adjusted associations of childhood meat eating with waist to hip ratio (WHR), high-density lipoprotein cholesterol and fasting plasma glucose. RESULTS: Adjusted for age, childhood hunger, life-course socioeconomic position and current lifestyle childhood almost daily meat eating compared with less than weekly meat eating was associated with higher WHR (0.007, 95% CI 0.0003 to 0.01) in men but not women. No association with fasting glucose was observed. CONCLUSIONS: Given the potential limitations of this study, especially the crude nature of the exposure and modest findings, the results should be considered as preliminary. However, they do lend support to the hypothesis that the male epidemic of premature IHD and sexual divergence in IHD rates that occur with economic development may be nutritionally driven in childhood. In elucidating the developmental origins of non-communicable chronic diseases, more attention should be focused on the sociohistorical context and the role of puberty.",
"title": "Does childhood meat eating contribute to sex differences in risk factors for ischaemic heart disease in a developing population?"
},
{
"docid": "MED-2361",
"text": "The most common clinical manifestation of Lyme disease is the characteristic rash, erythema migrans (EM). In the 1980s EM-like eruptions were reported in Missouri and other southeastern states. The EM-like eruptions, which were of unknown etiology, often followed the bite of the Lone Star tick (Amblyomma americanum) and the rash is called STARI (southern tick-associated rash illness). Although the Lone Star tick is found in the Lyme disease-endemic areas of New England and Mid-Atlantic regions of the United States, STARI has been reported only once from the Northeast and Mid-Atlantic regions. We report a child from Connecticut who visited Long Island, New York, and developed a rash that was thought to be EM. Because the patient failed to respond to antibiotics used to treat Lyme disease, an investigation ensued, and the diagnosis of STARI was established.",
"title": "Southern Tick-Associated Rash Illness (STARI) in the North: STARI following a tick bite in Long Island, New York."
},
{
"docid": "MED-3776",
"text": "Little research has examined the effect of water consumption on cognition in children. We examined whether drinking water improves performance from baseline to test in twenty-three 6-7-year-old children. There were significant interactions between time of test and water group (water/no water), with improvements in the water group on thirst and happiness ratings, visual attention and visual search, but not visual memory or visuomotor performance. These results indicate that even under conditions of mild dehydration, not as a result of exercise, intentional water deprivation or heat exposure, children's cognitive performance can be improved by having a drink of water.",
"title": "Does having a drink help you think? 6-7-Year-old children show improvements in cognitive performance from baseline to test after having a drink of ..."
},
{
"docid": "MED-4897",
"text": "Consumption of cow's milk and cow's milk protein result in changes of the hormonal axis of insulin, growth hormone and insulin-like growth factor-1(IGF-1) in humans. Milk consumption raises IGF-1 serum levels in the perinatal period, adolescence and adulthood. During puberty with the physiological onset of increased secretion of growth hormone, IGF-1 serum levels increase and are further enhanced by milk consumption. IGF-1 is a potent mitogen; after binding to its receptor in various tissues, it induces cell proliferation and inhibits apoptosis. Keratinocytes and sebocytes, as well as the androgen-synthesizing adrenals and gonads, are stimulated by IGF-1. The epidemic incidence of adolescent acne in Western milk-consuming societies can be explained by the increased insulin- and IGF-1-stimulation of sebaceous glands mediated by milk consumption. Acne can be regarded as a model for chronic Western diseases with pathologically increased IGF-1-stimulation. Many other organs, such as the thymus, bones, all glands, and vascular smooth muscle cells as well as neurons are subject to this abnormally increased hormonal stimulation. The milk-induced change of the IGF-1-axis most likely contributes to the development of fetal macrosomia, induction of atopy, accelerated linear growth, atherosclerosis, carcinogenesis and neurodegenerative diseases. Observations of molecular biology are supported by epidemiologic data and unmask milk consumption as a promoter of chronic diseases of Western societies.",
"title": "Milk consumption: aggravating factor of acne and promoter of chronic diseases of Western societies."
},
{
"docid": "MED-2826",
"text": "Background Curcumin extracts of turmeric are proposed to produce health benefits. To date, human intervention studies have focused mainly on people with existing health problems given high doses of poorly absorbed curcumin. The purpose of the current study was to check whether in healthy people, a low dose of a lipidated curcumin extract could alter wellness-related measures. Methods The present study was conducted in healthy middle aged people (40–60 years old) with a low dose of curcumin (80 mg/day) in a lipidated form expected to have good absorption. Subjects were given either curcumin (N = 19) or placebo (N = 19) for 4 wk. Blood and saliva samples were taken before and after the 4 weeks and analyzed for a variety of blood and saliva measures relevant to health promotion. Results Curcumin, but not placebo, produced the following statistically significant changes: lowering of plasma triglyceride values, lowering of salivary amylase levels, raising of salivary radical scavenging capacities, raising of plasma catalase activities, lowering of plasma beta amyloid protein concentrations, lowering of plasma sICAM readings, increased plasma myeloperoxidase without increased c-reactive protein levels, increased plasma nitric oxide, and decreased plasma alanine amino transferase activities. Conclusion Collectively, these results demonstrate that a low dose of a curcumin-lipid preparation can produce a variety of potentially health promoting effects in healthy middle aged people.",
"title": "Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people"
},
{
"docid": "MED-2655",
"text": "Background Broad dietary patterns have been linked to asthma but the relative contribution of specific nutrients is unclear. Soy genistein has important anti-inflammatory and other biological effects that might be beneficial in asthma. A positive association was previously reported between soy genistein intake and lung function but not with asthma exacerbations. Aims To conduct a post-hoc analysis of patients with inadequately controlled asthma enrolled in a prospective multicentre clinical trial to replicate this association. Methods A total of 300 study participants were included in the analysis. Dietary soy genistein intake was measured using the Block Soy Foods Screener. The level of soy genistein intake (little or no intake, moderate intake, or high intake) was compared with baseline lung function (pre-bronchodilator forced expiratory volume in 1 second (FEV1)) and asthma control (proportion of participants with an episode of poor asthma control (EPAC) and annualised rates of EPACs over a 6-month follow-up period. Results Participants with little or no genistein intake had a lower baseline FEV1 than those with a moderate or high intake (2.26L vs. 2.53L and 2.47L, respectively; p=0.01). EPACs were more common among those with no genistein intake than in those with a moderate or high intake (54% vs. 35% vs. 40%, respectively; p<0.001). These findings remained significant after adjustment for patient demographics and body mass index. Conclusions In patients with asthma, consumption of a diet with moderate to high amounts of soy genistein is associated with better lung function and better asthma control.",
"title": "Association of dietary soy genistein intake with lung function and asthma control: a post-hoc analysis of patients enrolled in a prospective multicentre clinical trial"
},
{
"docid": "MED-3458",
"text": "The single cell gel electrophoresis (SCG) assay (comet assay) is a sensitive technique for detecting the presence of DNA strand-breaks and alkali-labile damage in individual cells. This technique was used to study peripheral blood cells from three volunteers after physical activity. The test subjects had to run on a treadmill and were checked for blood pressure and ECG, lactate concentration and creatine kinase activity. Blood was taken before and several times during and after the run. In a first multiple step test, the volunteers ran as long as possible with increasing speed. In a second test they had to run for 45 min with a fixed individual speed which was defined to ensure an aerobic metabolism. In the first test, the white blood cells of all subjects showed increased DNA migration in the SCG assay. The effect was seen 6 h after the end of the exercise and reached its maximum 24 h later. After 72 h, DNA migration decreased to about control level. The distribution of DNA migration among cells clearly demonstrated that the majority of white blood cells exhibited increased DNA migration and that the effect was not only due to a small fraction of damaged cells. From the same blood samples, blood cultures were set up to study a possible effect on the frequency of sister chromatid exchanges (SCE), another indicator for genotoxic effects. However, there was no significant increase in SCE in any of the cultures. In the second exercise, during aerobic metabolism, the effect on DNA migration was not seen.(ABSTRACT TRUNCATED AT 250 WORDS)",
"title": "Does physical activity induce DNA damage?"
},
{
"docid": "MED-2586",
"text": "A systematic review and meta-analysis were carried out to study the effects of low-carbohydrate diet (LCD) on weight loss and cardiovascular risk factors (search performed on PubMed, Cochrane Central Register of Controlled Trials and Scopus databases). A total of 23 reports, corresponding to 17 clinical investigations, were identified as meeting the pre-specified criteria. Meta-analysis carried out on data obtained in 1,141 obese patients, showed the LCD to be associated with significant decreases in body weight (-7.04 kg [95% CI -7.20/-6.88]), body mass index (-2.09 kg m(-2) [95% CI -2.15/-2.04]), abdominal circumference (-5.74 cm [95% CI -6.07/-5.41]), systolic blood pressure (-4.81 mm Hg [95% CI -5.33/-4.29]), diastolic blood pressure (-3.10 mm Hg [95% CI -3.45/-2.74]), plasma triglycerides (-29.71 mg dL(-1) [95% CI -31.99/-27.44]), fasting plasma glucose (-1.05 mg dL(-1) [95% CI -1.67/-0.44]), glycated haemoglobin (-0.21% [95% CI -0.24/-0.18]), plasma insulin (-2.24 micro IU mL(-1) [95% CI -2.65/-1.82]) and plasma C-reactive protein, as well as an increase in high-density lipoprotein cholesterol (1.73 mg dL(-1) [95%CI 1.44/2.01]). Low-density lipoprotein cholesterol and creatinine did not change significantly, whereas limited data exist concerning plasma uric acid. LCD was shown to have favourable effects on body weight and major cardiovascular risk factors; however the effects on long-term health are unknown. © 2012 The Authors. obesity reviews © 2012 International Association for the Study of Obesity.",
"title": "Systematic review and meta-analysis of clinical trials of the effects of low carbohydrate diets on cardiovascular risk factors."
},
{
"docid": "MED-4058",
"text": "A facile method was established to measure heterocyclic aromatic amines (HAAs) accumulated in human hair and rodent fur. The samples were digested by base hydrolysis, and the liberated HAAs were isolated by tandem solvent/solid-phase extraction. Quantification was done by liquid chromatography/tandem mass spectrometry, using a triple stage quadrupole mass spectrometer in the selected reaction monitoring mode. In a pilot study of 12 human volunteers, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was detected in hair of six meat-eaters at levels ranging from 290 to 890 pg/g hair. 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-9H-pyrido[2,3-b]indole (AαC) were below the limit of quantification (LOQ) (50 pg/g hair) in hair from meat-eaters and six vegetarians. PhIP was detected in the hair from one vegetarian, and at level just above the LOQ (65 pg/g hair), indicating PhIP exposure occurs primarily through meat consumption. The levels of PhIP in hair samples from two meat-eaters varied by less than 24% over a 6-month interval, signifying that the exposure to PhIP and its accumulation in hair are relatively constant over time. In a controlled feeding study, female C57BL/6 mice were given these HAAs in their drinking water for 1 month, at six daily dose concentrations ranging from 0, 0.080 to 800 µg/kg body weight. PhIP was detected in fur of mice at all doses, whereas AαC and MeIQx were detected in fur at dosages ≥0.8 µg AαC/kg body weight and ≥8 µg MeIQx/kg body weight. There was a strong positive relationship between dosage and each of the HAAs accumulated in fur and their DNA adducts formed in liver and colon (p-values <0.0001); however, the levels of HAA in fur did not correlate to the levels of DNA adducts after adjustment of dose. Thus, hair appears to be a promising long-lived biomarker with by which we can assess the exposure to PhIP, a potential human carcinogen.",
"title": "Biomonitoring of Carcinogenic Heterocyclic Aromatic Amines in Hair: A Validation Study"
},
{
"docid": "MED-2293",
"text": "The CODEX Alimentarius definition of dietary fiber includes all nondigestible carbohydrate polymers with a degree of polymerization of 3 or more as dietary fiber with the proviso that they show health benefits. The global definition, if accepted by all authoritative bodies, offers a chance for international harmonization in research, food composition tables, and food labeling. Its nonacceptance highlights problems that may develop when definitions vary by region. The definition requires that the research community agrees upon physiological effects for which there is substantial scientific agreement, e.g., fibers’ effects on laxation and gut health, on attenuating blood lipids and blood glucose and insulin, and in promoting fermentation in the large bowel. The definition also necessitates the delineation of research protocols to prove the benefits of various isolated and synthesized fibers. These should emanate from evidence-based reviews that fairly weigh epidemiological data while considering that added fibers are not reflected in many food composition databases. They then should include well-controlled, randomized, control trials and utilize animal studies to determine mechanisms. Agreement on many study variables such as the type of subject and the type of baseline diet that best fits the question under investigation will also be needed. Finally, the definition establishes that all types of fiber can address the severe fiber consumption gap that exists throughout the world by recognizing that the combination of fiber-rich and -fortified foods increases fiber intake while allowing consumers to stay within allowed energy levels.",
"title": "Dietary Fiber Future Directions: Integrating New Definitions and Findings to Inform Nutrition Research and Communication"
},
{
"docid": "MED-3959",
"text": "Context: Earlier age at menarche is associated with rapid infancy weight gain and childhood obesity. The role of hormone levels in mediating these associations is unclear. Objective: The aim of this study was to identify childhood hormone levels at age 8 yr that are associated with early menarche, independent of body size. Design, Settings, and Subjects: A total of 329 girls from a prospective United Kingdom birth cohort study provided blood samples at mean age 8.1 yr (range, 8.0–8.5) for hormone measurements and were followed longitudinally to establish age at menarche. Main Outcome Measures: Fasting plasma levels of IGF-I, androstenedione, dehydroepiandrosterone sulfate (DHEAS), leptin, insulin, IGF binding protein-1, and SHBG were measured. Age at menarche was reported by questionnaire and categorized as before 12.0, 12.0–13.0, or later than 13 yr. Results: Earlier menarche was associated with greater body weight, height, and body mass index at age 8 yr (all P-trend <0.001). Before adjustment for body size, earlier menarche was associated with higher levels of IGF-I, androstenedione, DHEAS, leptin, and fasting insulin, and with lower levels of IGF binding protein-1 and SHBG at age 8 yr (all P < 0.01). After adjustment for body mass index and height at age 8 yr, only IGF-I (P = 0.004), androstenedione (P = 0.01), and DHEAS (P = 0.01) remained associated with earlier menarche. Conclusions: Associations between higher levels of IGF-I and adrenal androgens at age 8 yr with earlier menarche, independent of body size, support functional roles of these hormones in regulating puberty timing in girls. Higher levels of these hormones reported in children who exhibited rapid weight gain during infancy may indicate their role in developmental pathways leading to earlier sexual maturation.",
"title": "Higher Levels of IGF-I and Adrenal Androgens at Age 8 Years Are Associated with Earlier Age at Menarche in Girls"
},
{
"docid": "MED-2273",
"text": "Objective To examine and quantify the relation between purine intake and the risk of recurrent gout attacks among gout patients. Methods The authors conducted a case-crossover study to examine associations of a set of putative risk factors with recurrent gout attacks. Individuals with gout were prospectively recruited and followed online for 1 year. Participants were asked about the following information when experiencing a gout attack: the onset date of the gout attack, clinical symptoms and signs, medications (including antigout medications), and presence of potential risk factors (including daily intake of various purine-containing food items) during the 2-day period prior to the gout attack. The same exposure information was also assessed over 2-day control periods. Results This study included 633 participants with gout. Compared with the lowest quintile of total purine intake over a 2-day period, OR of recurrent gout attacks were 1.17, 1.38, 2.21 and 4.76, respectively, with each increasing quintile (p for trend <0.001). The corresponding OR were 1.42, 1.34, 1.77 and 2.41 for increasing quintiles of purine intake from animal sources (p for trend <0.001), and 1.12, 0.99, 1.32 and 1.39 from plant sources (p=0.04), respectively. The effect of purine intake persisted across subgroups by sex, use of alcohol, diuretics, allopurinol, NSAIDs and colchicine. Conclusions The study findings suggest that acute purine intake increases the risk of recurrent gout attacks by almost fivefold among gout patients. Avoiding or reducing amount of purine-rich foods intake, especially of animal origin, may help reduce the risk of gout attacks.",
"title": "Purine-rich foods intake and recurrent gout attacks"
},
{
"docid": "MED-3781",
"text": "In this study, a panel of normal human prostate cells (HPCs) and tumor cells derived from metastases were studied by (1)H NMR spectroscopy to determine whether the malignant transformation of HPCs results in the elevation of choline compounds. Although an elevated choline signal has been observed previously in clinical studies, the contribution of the different Cho compounds to this elevation, as well as their quantification, has not been established until now. Here we have shown that HPCs derived from metastases exhibit significantly higher phosphocholine as well as glycerophosphocholine levels compared with normal prostate epithelial and stromal cells. Thus the elevation of the choline peak observed clinically in prostate cancer is attributable to an alteration of phospholipid metabolism and not simply to increased cell density, doubling time, or other nonspecific effects. Androgen deprivation of the androgen receptor-positive cell lines resulted in a significant increase of choline compounds after chronic androgen deprivation of the LNCaP cell line and in a decrease of choline compounds after a more acute androgen deprivation of the LAPC-4 cell line. These data strongly support the use of proton magnetic resonance spectroscopic imaging to detect the presence of prostate cancer for diagnosis, to detect response subsequent to androgen ablation therapy, and to detect recurrence.",
"title": "Detection of increased choline compounds with proton nuclear magnetic resonance spectroscopy subsequent to malignant transformation of human prosta..."
},
{
"docid": "MED-2363",
"text": "We have previously shown that an antibody pool present in normal human serum binds cytokine receptors in vitro and may therefore interfere with assays that capture cytokines using their receptors. Here we show that this antibody pool is the same as the natural antibody termed anti-gal, that binds to the alpha-galactosyl carbohydrate epitope (alpha-gal) and which is the predominant obstacle to xenotransplantation. We report that there are high levels of IgD anti alpha-gal in most volunteers, in addition to the IgG2, IgA and IgM immunoglobulin isotypes against alpha-gal previously described. To determine if anti-gal may interfere with assays that depend on capture of cytokine with its receptor, we measured levels of several anti-carbohydrate antibodies in a cohort of patients with advanced atherosclerosis that had previously been used to measure levels of active TGF-beta using such an assay. For many isotype / carbohydrate combinations, there is a large and significant difference between the levels of anti-carbohydrate antibodies in patients with atherosclerosis and controls, after adjustment for age, sex and blood group. These results are similar to the previous data obtained for active TGF-beta, and therefore we cannot discount the possibility that anti-gal contributed to the previous data. Following further adjustment for several risk factors associated with cardiovascular disease, several anti-carbohydrate antibodies were still significantly different between patients and controls. Therefore, anti-carbohydrate antibodies may represent a new class of risk factors that may be associated with presence of advanced atherosclerosis, although larger studies will be required to confirm this hypothesis.",
"title": "A pattern of anti-carbohydrate antibody responses present in patients with advanced atherosclerosis."
},
{
"docid": "MED-1609",
"text": "To examine extra-alimentary effects of high-carbohydrate, high-fiber (HCF) diets, insulin-mediated glucose disposal employing the euglycemic clamp and hepatic glucose output (HGO) employing [6,6-2H2]glucose were measured in 12 healthy young and old individuals before and after 21-28 d of an HCF diet. Diet lowered fasting concentrations of glucose from 5.3 +/- 0.2 to 5.1 +/- 0.1 mmol/L (p less than 0.01) and insulin from 66.0 +/- 7.9 to 49.5 +/- 5.7 pmol/L (p less than 0.01). Fasting serum cholesterol decreased from 5.17 +/- 0.18 to 3.80 +/- 0.20 mmol/L (p less than 0.01) in young individuals and from 6.15 +/- 0.52 to 4.99 +/- 0.49 mmol/L (p less than 0.01) in elderly individuals. Fasting serum triglyceride concentrations, basal HGO, and insulin suppression of HGO were unchanged by the diet. Glucose disposal rates increased from 18.87 +/- 1.66 before 23.87 +/- 2.78 mumol.kg-1.min-1 after the diet (p less than 0.02). Therefore, HCF diets may improve carbohydrate economy by enhanced peripheral sensitivity to insulin.",
"title": "High-carbohydrate, high-fiber diets increase peripheral insulin sensitivity in healthy young and old adults."
},
{
"docid": "MED-3927",
"text": "Objective: Epidemiologic studies consistently link caffeine, a nonselective adenosine antagonist, to lower risk of Parkinson disease (PD). However, the symptomatic effects of caffeine in PD have not been adequately evaluated. Methods: We conducted a 6-week randomized controlled trial of caffeine in PD to assess effects upon daytime somnolence, motor severity, and other nonmotor features. Patients with PD with daytime somnolence (Epworth >10) were given caffeine 100 mg twice daily ×3 weeks, then 200 mg twice daily ×3 weeks, or matching placebo. The primary outcome was the Epworth Sleepiness Scale score. Secondary outcomes included motor severity, sleep markers, fatigue, depression, and quality of life. Effects of caffeine were analyzed with Bayesian hierarchical models, adjusting for study site, baseline scores, age, and sex. Results: Of 61 patients, 31 were randomized to placebo and 30 to caffeine. On the primary intention-to-treat analysis, caffeine resulted in a nonsignificant reduction in Epworth Sleepiness Scale score (−1.71 points; 95% confidence interval [CI] −3.57, 0.13). However, somnolence improved on the Clinical Global Impression of Change (+0.64; 0.16, 1.13, intention-to-treat), with significant reduction in Epworth Sleepiness Scale score on per-protocol analysis (−1.97; −3.87, −0.05). Caffeine reduced the total Unified Parkinson's Disease Rating Scale score (−4.69 points; −7.7, −1.6) and the objective motor component (−3.15 points; −5.50, −0.83). Other than modest improvement in global health measures, there were no changes in quality of life, depression, or sleep quality. Adverse events were comparable in caffeine and placebo groups. Conclusions: Caffeine provided only equivocal borderline improvement in excessive somnolence in PD, but improved objective motor measures. These potential motor benefits suggest that a larger long-term trial of caffeine is warranted. Classification of evidence: This study provides Class I evidence that caffeine, up to 200 mg BID for 6 weeks, had no significant benefit on excessive daytime sleepiness in patients with PD.",
"title": "Caffeine for treatment of Parkinson disease"
},
{
"docid": "MED-4308",
"text": "We examined the occurrence and coincidence of depressed mood and excessive carbohydrate intake in 19 patients who claimed to suffer from severe premenstrual syndrome and in nine control subjects, all as inpatients, during the early follicular and late luteal phases of their menstrual cycles. Mood was assessed with the Hamilton Depression Scale and an addendum that evaluated fatigue, sociability, appetite, and carbohydrate craving. Calorie and nutrient intakes were measured directly. The subjects with premenstrual syndrome significantly increased calorie intake during the late luteal phase (from 1892 +/- 104 to 2395 +/- 93 kcal, mean +/- SEM); carbohydrate intake increased by 24% from meals and by 43% from snacks. Protein intake failed to change, whereas intake of fat, a fixed constituent of all of the test foods, rose in proportion to calorie intake. The Hamilton Depression Scale and addendum scores rose from 2.0 +/- 0.5 to 21.2 +/- 0.8 (Hamilton Scale) and from 0.5 +/- 0.5 to 10.2 +/- 0.6 (addendum) among subjects with premenstrual syndrome during the luteal phase but failed to change among the controls (2.1 +/- 0.8 to 2.4 +/- 0.8, and 0.4 +/- 0.3 to 0.6 +/- 0.3). Consumption of a carbohydrate-rich, protein-poor evening test meal during the late luteal phase of the menstrual cycle improved depression, tension, anger, confusion, sadness, fatigue, alertness, and calmness scores (p less than 0.01) among patients with premenstrual syndrome. No effect of the meal was observed during the follicular phase or among the control subjects during either phase. Because synthesis of brain serotonin, which is known to be involved in mood and appetite, increases after carbohydrate intake, premenstrual syndrome subjects may overconsume carbohydrates in an attempt to improve their dysphoric mood state.",
"title": "Effect of nutrient intake on premenstrual depression."
},
{
"docid": "MED-2510",
"text": "Dietary restriction (DR) extends the lifespan of a wide range of species, although the universality of this effect has never been quantitatively examined. Here, we report the first comprehensive comparative meta-analysis of DR across studies and species. Overall, DR significantly increased lifespan, but this effect is modulated by several factors. In general, DR has less effect in extending lifespan in males and also in non-model organisms. Surprisingly, the proportion of protein intake was more important for life extension via DR than the degree of caloric restriction. Furthermore, we show that reduction in both age-dependent and age-independent mortality rates drives life extension by DR among the well-studied laboratory model species (yeast, nematode worms, fruit flies and rodents). Our results suggest that convergent adaptation to laboratory conditions better explains the observed DR-longevity relationship than evolutionary conservation although alternative explanations are possible. © 2012 The Authors. Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.",
"title": "Comparative and meta-analytic insights into life extension via dietary restriction."
},
{
"docid": "MED-3771",
"text": "OBJECTIVE: Hyperosmotic stress on cells limits many aspects of cell function, metabolism and health. International data suggest that schoolchildren may be at risk of hyperosmotic stress on cells because of suboptimal water intake. The present study explored the cell hydration status of two samples of children in the USA. DESIGN: Cross-sectional study describing the urine osmolality (an index of hyperosmotic cell shrinkage) and water intake of convenience samples from Los Angeles (LA) and New York City (NYC). SETTING: Each participant collected a urine sample at an outpatient clinic on the way to school on a weekday morning in spring 2009. Each was instructed to wake, eat, drink and do as usual before school, and complete a dietary record form describing the type and amounts of all foods and beverages consumed after waking, before giving the sample. SUBJECTS: The children (9-11 years) in LA (n 337) and NYC (n 211) considered themselves healthy enough to go to school on the day they gave the urine sample. RESULTS: Elevated urine osmolality (>800 mmol/kg) was observed in 63 % and 66 % of participants in LA and NYC, respectively. In multivariable-adjusted logistic regression models, elevated urine osmolality was associated with not reporting intake of drinking water in the morning (LA: OR = 2·1, 95 % CI 1·2, 3·5; NYC: OR = 1·8, 95 % CI 1·0, 3·5). Although over 90 % of both samples had breakfast before giving the urine sample, 75 % did not drink water. CONCLUSIONS: Research is warranted to confirm these results and pursue their potential health implications.",
"title": "What is the cell hydration status of healthy children in the USA? Preliminary data on urine osmolality and water intake."
},
{
"docid": "MED-4306",
"text": "When plasma tryptophan is elevated by the injection of tryptophan or insulin, or by the consumption of carbohydrates, brain tryptophan and serotonin also rise; however, when even larger elevations of plasma tryptophan are produced by the ingestion of protein-containing diets, brain tryptophan and serotonin do not change. The main determinant of brain tryptophan and serotonin concentrations does not appear to be plasma tryptophan alone, but the ratio of this amino acid to other plasma neutral amino acids (that is, tyrosine, phenylalanine, leucine, isoleucine, and valine) that compete with it for uptake into the brain.",
"title": "Brain serotonin content: physiological regulation by plasma neutral amino acids."
},
{
"docid": "MED-3930",
"text": "Studies that have addressed the association between the intake of coffee or caffeine and Parkinson's disease (PD) were conducted mainly in Western countries. Little is known about this relationship in an Asian population. Therefore, we performed an assessment of the association of the intake of coffee, other caffeine-containing beverages, and caffeine with the risk of PD in Japan. The study involved 249 PD cases and 368 control subjects. Information on dietary factors was obtained through a self-administered diet history questionnaire. Adjustment was made for sex, age, region of residence, educational level, pack-years of smoking, body mass index, the dietary glycemic index, and intake of cholesterol, vitamin E, β-carotene, vitamin B(6,) alcohol, and iron. Intake of coffee, black tea, and Japanese and Chinese teas was significantly inversely associated with the risk of PD: the adjusted odds ratios in comparison of the highest with the lowest quartile were 0.52, 0.58, and 0.59, respectively (95% confidence intervals = 0.30-0.90, 0.35-0.97, and 0.35-0.995, respectively). A clear inverse dose-response relationship between total caffeine intake and PD risk was observed. We confirmed that the intake of coffee and caffeine reduced the risk of PD. Furthermore, this is the first study to show a significant inverse relationship between the intake of Japanese and Chinese teas and the risk of PD. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Intake of Japanese and Chinese teas reduces risk of Parkinson's disease."
},
{
"docid": "MED-4953",
"text": "Objective To evaluate whether intake of protein from animal and vegetable origin is associated with ovulatory infertility. Study Design 18,555 married women without a history of infertility were followed as they attempted a pregnancy or became pregnant during an eight year period. Dietary assessments were related to the incidence of ovulatory infertility. Results During follow-up, 438 women reported ovulatory infertility. The multivariate-adjusted relative risk [RR] (95% CI; P, trend) of ovulatory infertility comparing the highest to the lowest quintile of animal protein intake was 1.39 (1.01 – 1.90; 0.03). The corresponding RR (95% CI; P, trend) for vegetable protein intake was 0.78 (0.54 – 1.12; 0.07). Further, consuming 5% of total energy intake as vegetable protein rather than as animal protein was associated with a more than 50% lower risk of ovulatory infertility (P = 0.007). Conclusions Replacing animal sources of protein with vegetable sources of protein may reduce ovulatory infertility risk.",
"title": "Protein intake and ovulatory infertility"
},
{
"docid": "MED-1611",
"text": "A growing body of evidence from observational studies and meta-analyses of the data suggest that diabetes mellitus is associated with an increased risk of cancer. Meta-analyses have shown that diabetes increases the risks of total cancer, and of site-specific cancers of the breast, endometrium, bladder, liver, colorectum and pancreas, and that it decreases the risk of prostate cancer. Insulin resistance and secondary hyperinsulinemia is the most frequently proposed hypothesis, and hyperglycemia itself might promote carcinogenesis. In addition to several facets of lifestyle including obesity, smoking and lack of exercise, treatment for diabetes might affect the risk of cancer. For instance, metformin, an insulin sensitizer, reportedly has a potential anticancer effect. In light of the exploding global epidemic of diabetes, even a modest increase in the cancer risk will translate into a substantial socioeconomic burden. The current insights underscore the need for clinical attention and better-designed studies of the complex interactions between diabetes and cancer.",
"title": "Latest insights into the risk of cancer in diabetes"
},
{
"docid": "MED-3449",
"text": "Watercress (Cruciferae), an integral part of Mediterranean diets, is a nutritive food which is used in the treatment of several diseases. Oxidative DNA damage seems to play a crucial role in chronic, aging-related diseases and it is considered an important and probably carcinogenic factor. The aim of this work was to determine the impact of watercress extract on cell viability and its potential antigenotoxic properties against induced oxidative damage, using a comet assay and peripheral blood cells as an in vitro model. An aqueous extract of the leaves was prepared using a juice processor, centrifuged, filtered and preserved at -20 °C. Two concentrations of the aqueous extract (13.2 and 26.4 mg/mL) were assayed. No differences were found in cell viability between the control and treated groups at any time. Significant antigenotoxic effects were observed for both concentrations, expressed as the damage index (p = 0.005 at 30 min; p < 0.001 at 60 and 90 min), the percentage reductions in damage being similar between them (67.1-75.2% respectively). These results suggest that the consumption watercress in the diet is a powerful tool for improving health and the quality of life. Copyright © 2011 John Wiley & Sons, Ltd.",
"title": "Antigenotoxic activity of watercress extract in an in vitro mammalian system using comet assay."
},
{
"docid": "MED-1582",
"text": "Background & Aims Increased intake of dietary fiber has been proposed to reduce risk of inflammatory bowel diseases (Crohn’s disease [CD], ulcerative colitis [UC]). However, few prospective studies have examined associations between long-term intake of dietary fiber and risk of incident CD or UC. Methods We collected and analyzed data from 170,776 women, followed over 26 y, who participated in the Nurses’ Health Study, followed for 3,317,425 person-y. Dietary information was prospectively ascertained via administration of a validated semi-quantitative food frequency questionnaire every 4 y. Self-reported CD and UC were confirmed through review of medical records. Cox proportional hazards models, adjusting for potential confounders, were used to calculate hazard ratios (HRs). Results We confirmed 269 incident cases of CD (incidence 8/100,000 person-y) and 338 cases of UC (incidence 10/100,000 person-y). Compared to the lowest quintile of energy-adjusted cumulative average intake of dietary fiber, intake of the highest quintile (median of 24.3 g/day) was associated with a 40% reduction in risk of CD (multivariate HR for CD, 0.59; 95% confidence interval [CI], 0.39–0.90). This apparent reduction appeared to be greatest for fiber derived from fruits; fiber from cereals, whole grains, or legumes did not modify risk. In contrast, neither total intake of dietary fiber (multivariate HR, 0.82; 95% CI 0.58–1.17) nor intake of fiber from specific sources appeared to be significantly associated with risk of UC. Conclusion Based on data from the Nurses’ Health Study, long-term intake of dietary fiber, particularly from fruit, is associated with lower risk of CD but not UC. Further studies are needed to determine the mechanisms that mediate this association.",
"title": "A Prospective Study of Long-term Intake of Dietary Fiber and Risk of Crohn’s Disease and Ulcerative Colitis"
},
{
"docid": "MED-2662",
"text": "A human breast cancer cell line (MCF-7) was used to develop an in vitro screening assay for the detection of xenoestrogenic environmental pollutants. MCF-7 cells were cultured in DMEM containing 5% fetal bovine serum (FBS). An estrogenic response was defined as an increase in the frequency of proliferating MCF-7 cells, and was measured using a thymidine analog, bromodeoxyuridine, and flow cytometry. Di-2-ethylhexyl phthalate (DEHP) and 4-n-nonylphenol (4-n-NP) were used as model chemicals. The proliferation rate of S-phase cells after 24 h of exposure to various concentrations of 17beta-estradiol and to model compounds was compared with a positive and a negative control, containing 1 nM 17beta-estradiol and 0.1% ethanol, respectively. DEHP and 4-n-NP increased the frequency of proliferating MCF-7 cells in a dose-dependent manner. The lowest concentration that significantly increased the proliferation of MCF-7 cells was 10 microM for DEHP and 1 microM for 4-n-NP. The results showed that the assay is accurate and quick to perform. It may prove a valuable tool for screening potential estrogen-mimicking environmental pollutants.",
"title": "Effects of xenoestrogenic environmental pollutants on the proliferation of a human breast cancer cell line (MCF-7)."
},
{
"docid": "MED-5182",
"text": "BACKGROUND: Reports of relationships between dietary fibre intake and breast cancer have been inconsistent. Previous cohort studies have been limited by a narrow range of intakes. METHODS: Women who developed invasive breast cancer, 350 post-menopausally and 257 pre-menopausally, during 240,959 person-years of follow-up in the UK Women's Cohort Study (UKWCS) were studied. This cohort has 35,792 subjects with a wide range of exposure to dietary fibre with intakes of total fibre in the lowest quintile of <20 g/day up to >30 g/day in the top quintile. Fibre and breast cancer relationships were explored using Cox regression modelling adjusted for measurement error. Effects of fibre, adjusting for confounders were examined for pre- and post-menopausal women separately. RESULTS: In pre-menopausal, but not post-menopausal women a statistically significant inverse relationship was found between total fibre intake and risk of breast cancer (P for trend = 0.01). The top quintile of fibre intake was associated with a hazard ratio of 0.48 [95% confidence interval (CI) 0.24-0.96] compared with the lowest quintile. Pre-menopausally, fibre from cereals was inversely associated with risk of breast cancer (P for trend = 0.05) and fibre from fruit had a borderline inverse relationship (P for trend = 0.09). A further model including dietary folate strengthened the significance of the inverse relationship between total fibre and pre-menopausal breast cancer. CONCLUSIONS: These findings suggest that in pre-menopausal women, total fibre is protective against breast cancer; in particular, fibre from cereals and possibly fruit.",
"title": "Dietary fibre and risk of breast cancer in the UK Women's Cohort Study."
},
{
"docid": "MED-1187",
"text": "Background and aims: The causes of relapses of ulcerative colitis (UC) are unknown. Dietary factors have been implicated in the pathogenesis of UC. The aim of this study was to determine which dietary factors are associated with an increased risk of relapse of UC. Methods: A prospective cohort study was performed with UC patients in remission, recruited from two district general hospitals, who were followed for one year to determine the effect of habitual diet on relapse. Relapse was defined using a validated disease activity index. Nutrient intake was assessed using a food frequency questionnaire and categorised into tertiles. Adjusted odds ratios for relapse were determined using multivariate logistic regression, controlling for non-dietary factors. Results: A total of 191 patients were recruited and 96% completed the study. Fifty two per cent of patients relapsed. Consumption of meat (odds ratio (OR) 3.2 (95% confidence intervals (CI) 1.3–7.8)), particularly red and processed meat (OR 5.19 (95% CI 2.1–12.9)), protein (OR 3.00 (95% CI 1.25–7.19)), and alcohol (OR 2.71 (95% CI 1.1–6.67)) in the top tertile of intake increased the likelihood of relapse compared with the bottom tertile of intake. High sulphur (OR 2.76 (95% CI 1.19–6.4)) or sulphate (OR 2.6 (95% CI 1.08–6.3)) intakes were also associated with relapse and may offer an explanation for the observed increased likelihood of relapse. Conclusions: Potentially modifiable dietary factors, such as a high meat or alcoholic beverage intake, have been identified that are associated with an increased likelihood of relapse for UC patients. Further studies are needed to determine if it is the sulphur compounds within these foods that mediates the likelihood of relapse and if reducing their intake would reduce relapse frequency.",
"title": "Influence of dietary factors on the clinical course of ulcerative colitis: a prospective cohort study"
},
{
"docid": "MED-3226",
"text": "Context and Objective: Dietary intake of animal proteins is associated with an increase in urinary calcium and nephrolithiasis risk. We tested the hypothesis that the acid load imposed by dietary proteins causes this hypercalciuria. Design and Setting: In a short-term crossover metabolic study, an alkali salt was provided with a high-protein diet (HPD) to neutralize the acid load imparted by dietary proteins. Participants and Interventions: Eleven healthy volunteers were evaluated at the end of each of four phases while consuming metabolic diets with fixed calcium and sodium content. Phases 1 and 3 consisted of a control diet (CD). Phases 2 and 4 consisted of a eucaloric HPD (60 g/d animal proteins added to CD). Along with HPD in phases 2 and 4, subjects ingested 30 mEq twice daily of either potassium citrate (KCitrate, alkaline salt) or potassium chloride (KCl, control neutral salt). Results: KCitrate completely neutralized the acid load imparted by HPD (based on changes in urine pH and net acid excretion) and increased urinary citrate. Urinary calcium increased during both HPD phases compared with CD but was not significantly different between the HPD + KCl and HPD + KCitrate phases (182 ± 85 vs. 170 ± 85 mg/d; P = 0.28). Increased urinary saturation with respect to calcium oxalate and uric acid with HPD was abrogated by KCitrate. Conclusions: This study suggests that, at least in the short-term, mechanism(s) other than acid load account for hypercalciuria induced by HPD. The beneficial effect of KCitrate on nephrolithiasis risk with HPD is through correction of declines in urine pH and citrate.",
"title": "Hypercalciuria Associated with High Dietary Protein Intake Is Not Due to Acid Load"
},
{
"docid": "MED-2506",
"text": "Long-term caloric restriction (CR) is a robust means of reducing age-related diseases and extending life span in multiple species, but the effects in humans are unknown. The low caloric intake, long life expectancy, and the high prevalence of centenarians in Okinawa have been used as an argument to support the CR hypothesis in humans. However, no long-term, epidemiologic analysis has been conducted on traditional dietary patterns, energy balance, and potential CR phenotypes for the specific cohort of Okinawans who are purported to have had a calorically restricted diet. Nor has this cohort's subsequent mortality experience been rigorously studied. Therefore, we investigated six decades of archived population data on the elderly cohort of Okinawans (aged 65-plus) for evidence of CR. Analyses included traditional diet composition, energy intake, energy expenditure, anthropometry, plasma DHEA, mortality from age-related diseases, and current survival patterns. Findings include low caloric intake and negative energy balance at younger ages, little weight gain with age, life-long low BMI, relatively high plasma DHEA levels at older ages, low risk for mortality from age-related diseases, and survival patterns consistent with extended mean and maximum life span. This study lends epidemiologic support for phenotypic benefits of CR in humans and is consistent with the well-known literature on animals with regard to CR phenotypes and healthy aging.",
"title": "Caloric restriction, the traditional Okinawan diet, and healthy aging: the diet of the world's longest-lived people and its potential impact on mor..."
},
{
"docid": "MED-1254",
"text": "OBJECTIVE: To investigate the effect of replacing lean meat with a soy product, tofu, on coronary heart disease risk factors including serum lipoproteins, lipoprotein (a), factor VII, fibrinogen and in vitro susceptibility of LDL to oxidation. DESIGN: A randomized cross over dietary intervention study. SETTING: Free-living individuals studied at Deakin University. SUBJECTS: Forty-five free-living healthy males aged 35 to 62 years completed the dietary intervention. Three subjects were non-compliant and excluded prior to analysis. INTERVENTIONS: A diet containing 150 grams of lean meat per day was compared to a diet containing 290 grams of tofu per day in an isocaloric and isoprotein substitution. Each dietary period was one month duration. RESULTS: Analysis of the seven-day diet record showed that diets were similar in energy, protein, carbohydrate, total fat, saturated and unsaturated fat, polyunsaturated to saturated fat ratio, alcohol and fiber. Total cholesterol and triglycerides were significantly lower, and in vitro LDL oxidation lag phase was significantly longer on the tofu diet compared to the meat diet. The hemostatic factors, factor VII and fibrinogen, and lipoprotein(a) were not significantly affected by the tofu diet. CONCLUSIONS: The increase in LDL oxidation lag phase would be expected to be associated with a decrease in coronary heart disease risk.",
"title": "Effect of meat replacement by tofu on CHD risk factors including copper induced LDL oxidation."
},
{
"docid": "MED-2272",
"text": "To assess the physiologic effects of cherry consumption, we measured plasma urate, antioxidant and inflammatory markers in 10 healthy women who consumed Bing sweet cherries. The women, age 22-40 y, consumed two servings (280 g) of cherries after an overnight fast. Blood and urine samples were taken before the cherry dose, and at 1.5, 3 and 5 h postdose. Plasma urate decreased 5 h postdose, mean +/- SEM = 183 +/- 15 micro mol/L compared with predose baseline of 214 +/- 13 micro mol/L (P < 0.05). Urinary urate increased postdose, with peak excretion of 350 +/- 33 micro mol/mmol creatinine 3 h postdose compared with 202 +/- 13 at baseline (P < 0.01). Plasma C-reactive protein (CRP) and nitric oxide (NO) concentrations had decreased marginally 3 h postdose (P < 0.1), whereas plasma albumin and tumor necrosis factor-alpha were unchanged. The vitamin C content of the cherries was solely as dehydroascorbic acid, but postdose increases in plasma ascorbic acid indicated that dehydroascorbic acid in fruits is bioavailable as vitamin C. The decrease in plasma urate after cherry consumption supports the reputed anti-gout efficacy of cherries. The trend toward decreased inflammatory indices (CRP and NO) adds to the in vitro evidence that compounds in cherries may inhibit inflammatory pathways.",
"title": "Consumption of cherries lowers plasma urate in healthy women."
},
{
"docid": "MED-2504",
"text": "It is well established that the target of rapamycin (TOR) protein kinase has pivotal roles in controlling cell functions (including protein synthesis, cell growth and cell proliferation) and is implicated in numerous human diseases. Mammalian TOR complex 1 (mTORC1) signalling is activated by hormones and growth factors, and is also stimulated by intracellular amino acids. Recent research has provided important new insight into the poorly understood mechanism by which amino acids activate mTORC1 signalling, showing that the protein kinase MAP4K3 and Rag GTPases have important roles in this. mTORC1 is known to control the G1/S transition of the cell cycle: new data show that (m)TORC1 also controls G2/M progression in yeast and mammals, albeit in contrasting ways.",
"title": "Nutrient control of TORC1, a cell-cycle regulator."
},
{
"docid": "MED-4886",
"text": "OBJECTIVES: Previous research has demonstrated that patients with prostate cancer participating in the Prostate Cancer Lifestyle Trial had a reduction in prostate-specific antigen (PSA) levels, inhibition of LNCaP cell growth, and fewer prostate cancer-related clinical events at the end of 1 year compared with controls. The aim of this study was to examine the clinical events in this trial during a 2-year period. METHODS: The Prostate Cancer Lifestyle Trial was a 1-year randomized controlled clinical trial of 93 patients with early-stage prostate cancer (Gleason score <7, PSA 4-10 ng/mL) undergoing active surveillance. The patients in the experimental arm were encouraged to adopt a low-fat, plant-based diet, to exercise and practice stress management, and to attend group support sessions. The control patients received the usual care. RESULTS: By 2 years of follow-up, 13 of 49 (27%) control patients and 2 of 43 (5%) experimental patients had undergone conventional prostate cancer treatment (radical prostatectomy, radiotherapy, or androgen deprivation, P < .05). No differences were found between the groups in other clinical events (eg, cardiac), and no deaths occurred. Three of the treated control patients but none of the treated experimental patients had a PSA level of >or=10 ng/mL, and 1 treated control patient but no treated experimental patients had a PSA velocity of >2 ng/mL/y before treatment. No significant differences were found between the untreated experimental and untreated control patients in PSA change or velocity at the end of 2 years. CONCLUSIONS: Patients with early-stage prostate cancer choosing active surveillance might be able to avoid or delay conventional treatment for at least 2 years by making changes in their diet and lifestyle.",
"title": "Clinical events in prostate cancer lifestyle trial: results from two years of follow-up."
},
{
"docid": "MED-3271",
"text": "Most metastatic tumors, such as those originating in the prostate, lung, and gastrointestinal tract, respond poorly to conventional chemotherapy. Novel treatment strategies for advanced cancer are therefore desperately needed. Dietary restriction of the essential amino acid methionine offers promise as such a strategy, either alone or in combination with chemotherapy or other treatments. Numerous in vitro and animal studies demonstrate the effectiveness of dietary methionine restriction in inhibiting growth and eventually causing death of cancer cells. In contrast, normal host tissues are relatively resistant to methionine restriction. These preclinical observations led to a phase I clinical trial of dietary methionine restriction for adults with advanced cancer. Preliminary findings from this trial indicate that dietary methionine restriction is safe and feasible for the treatment of patients with advanced cancer. In addition, the trial has yielded some preliminary evidence of antitumor activity. One patient with hormone-independent prostate cancer experienced a 25% reduction in serum prostate-specific antigen (PSA) after 12 weeks on the diet, and a second patient with renal cell cancer experienced an objective radiographic response. The possibility that methionine restriction may act synergistically with other cancer treatments such as chemotherapy is being explored. Findings to date support further investigation of dietary methionine restriction as a novel treatment strategy for advanced cancer.",
"title": "Can dietary methionine restriction increase the effectiveness of chemotherapy in treatment of advanced cancer?"
},
{
"docid": "MED-3127",
"text": "AIM: Isoflavones in soy foods are part of a larger class of flayonoid compounds that have have been demonstrated to be potent dietary anti-cancer agents, and the effect of soy intake on the survival of ovarian cancer is conflicting. Therefore, we aimed to explore the whether soy intake is related to the risk of death of breast cancer. METHODS: A prospective study was conducted. A total of 256 patients included in this study had breast cancer and were recruited between January 2004 and January 2006. All of them were followed up from since January 2011. A univariate Cox's regression analysis was used to assess the association between soy intake and survival. RESULTS: The education level, menopausal status, ER/PR status and TNM stage were significant difference in the survival of breast cancer. The highest soy isoflavone was associated with a decreased death risk of breast cancer (OR=0.25, 95% CI=0.09-0.54). Moreover, the higher consumption of soy protein also presented a trend decreased breast cancer risk, and the highest consumption significantly reduced the cancer risk compared with the lowest consumption (OR=0.38, 95% CI=0.17-0.86). CONCLUSION: The present study suggests soy intake is associated with a significant reduced death risk of breast cancer in Chinese population. Further large sample studies are warranted to confirm the inverse association of soy consumption and breast cancer survival by menopausal status.",
"title": "Study on soy isoflavone consumption and risk of breast cancer and survival."
},
{
"docid": "MED-3230",
"text": "OBJECTIVE: Diet affects urine pH and acid-base balance. Both excess acid/alkaline ash (EAA) and estimated net acid excretion (NAE) calculations have been used to estimate the effects of diet on urine pH. This study's goal was to determine if free-living vegans, lacto-ovo vegetarians, and omnivores have increasingly acidic urine, and to assess the ability of EAA and estimated NAE calculations to predict urine pH. DESIGN: This study used a cross-sectional design. SETTING AND PARTICIPANTS: This study assessed urine samples of 10 vegan, 16 lacto-ovo vegetarian, and 16 healthy omnivorous women in the Boston metropolitan area. Six 3-day food records from each dietary group were analyzed for EAA content and estimated NAE, and correlations with measured urine pH were calculated. RESULTS: The mean (+/- SD) urine pH was 6.15 +/- 0.40 for vegans, 5.90 +/- 0.36 for lacto-ovo vegetarians, and 5.74 +/- 0.21 for omnivores (analysis of variance, P = .013). Calculated EAA values were not significantly different among the three groups, whereas mean estimated NAE values were significantly different: 17.3 +/- 14.5 mEq/day for vegans, 31.3 +/- 8.5 mEq/day for lacto-ovo vegetarians, and 42.6 +/- 13.2 mEq/day for omnivores (analysis of variance, P = .01). The average deattenuated correlation between urine pH and EAA was 0.333; this value was -0.768 for estimated NAE and urine pH, with a regression equation of pH = 6.33 - 0.014 NAE (P = .02, r = -0.54). CONCLUSIONS: Habitual diet and estimated NAE calculations indicate the probable ranking of urine pH by dietary groups, and may be used to determine the likely acid-base status of an individual; EAA calculations were not predictive of urine pH.",
"title": "Estimated net acid excretion inversely correlates with urine pH in vegans, lacto-ovo vegetarians, and omnivores."
},
{
"docid": "MED-3235",
"text": "Background Maintaining muscle mass while aging is important to prevent falls and fractures. Metabolic acidosis promotes muscle wasting, and the net acid load from diets that are rich in net acid–producing protein and cereal grains relative to their content of net alkali–producing fruit and vegetables may therefore contribute to a reduction in lean tissue mass in older adults. Objective We aimed to determine whether there was an association of 24-h urinary potassium and an index of fruit and vegetable content of the diet with the percentage lean body mass (%LBM) or change in %LBM in older subjects. Design Subjects were 384 men and women ≥65 y old who participated in a 3-y trial comparing calcium and vitamin D with placebo. Potassium was measured in 24-h urine collections at baseline. The %LBM, defined as total body nonfat, nonbone tissue weight ÷ weight × 100, was measured by using dual-energy X-ray absorptiometry at baseline and at 3 y. Physical activity, height, and weight were assessed at baseline and at 3 y. Results At baseline, the mean urinary potassium excretion was 67.0 ± 21.1 mmol/d. Urinary potassium (mmol/d) was significantly positively associated with %LBM at baseline (β = 0.033, P = 0.006; adjusted for sex, weight, and nitrogen excretion) but not with 3-y change in %LBM. Over the 3-y study, %LBM increased by 2.6 ± 3.6%. Conclusion Higher intake of foods rich in potassium, such as fruit and vegetables, may favor the preservation of muscle mass in older men and women.",
"title": "Alkaline diets favor lean tissue mass in older adults"
},
{
"docid": "MED-1618",
"text": "To study the effect of a moderate increase in insulin secretion produced by an increased daily protein intake on dehydroepiandrosterone sulfate (DHEAS), a balanced randomized crossover trial consisting of three strictly controlled dietary regimens was performed in six healthy male volunteers. The basic diet (B) contained 50 g protein/d; diets P and M (also basic diets) were enriched with either 32 g protein/d (P) or 10 mmol L-methionine/d (M). Methionine was given (as a specific nonprotein source of endogenously derived sulfate) to control for possible confounding effects on DHEAS due to an increased sulfate supply. At the end of each 4-day diet period, blood and 24-hour urine samples were collected. Fasting plasma levels of testosterone, cortisol, insulin-like growth factor-I (IGF-I), and insulin, as well as urinary output of total (hot acid-cleaved) testosterone conjugates and 3alpha-androstanediol glucuronide, did not show significant changes in response to dietary manipulations. Endogenous sulfate availability (as reflected by renal sulfate output per 24 hours) approximately doubled with diets P and M. However, plasma levels (6.3 +/- 1.5, 6.8 +/- 1.8, and 6.9 +/- 2.1 micromol/L for B, P, and M, respectively) and urinary excretion (8.8 +/- 9.8, 9.4 +/- 11.2, 8.0 +/- 8.3 micromol/d) of DHEAS remained unaffected. Considering the clear increments (P < .01) in urinary C-peptide excretion with diet P (20.4 +/- 10.3 nmol/d) versus diets B and M (12.6 +/- 5.1 and 13.2 +/- 3.6 nmol/d), respectively, our results suggest that a moderately strong diet-induced increase in daily insulin secretion does not alter urinary and plasma levels of DHEAS.",
"title": "A moderate increase in daily protein intake causing an enhanced endogenous insulin secretion does not alter circulating levels or urinary excretion..."
},
{
"docid": "MED-2208",
"text": "BACKGROUND: Bikunin, a Kunitz-type protease inhibitor, specifically inhibits tumor invasion and metastasis. METHODS: The authors initially evaluated the therapeutic efficacy of once-daily oral administration of different doses of bikunin against human ovarian carcinoma HRA cells growing in the peritonea of nude mice. For the in vivo studies, female 7-week-old nude mice were randomized to 1 of 4 groups: bikunin-treated groups (n = 9 in each group) received 3, 10, or 30 microg/g body weight per day bikunin for 7 days via gastrointestinal gavage, and a control group (n = 9) received the vehicle solution (phosphate-buffered saline) via gastrointestinal gavage. On Day 9, the abdominal cavity was examined by two observers who were blinded to treatment. RESULTS: After oral administration, intact bikunin was detectable in mouse serum specimens at 3 and 6 hours. This was followed by a decline at 12 hours. The mice given bikunin at the highest dose level had a 40% decrease in tumor load. The highest uptake in the tumor was obtained with [125I]bikunin 12 hours postadministration. No effect on either food intake or body weight was observed in the treated versus sham groups. The current study was the first to report the potent activity of once-daily oral administration of bikunin against ovarian carcinoma. Next, the authors performed a Phase I trial to determine the maximum-tolerated dose (MTD) and safety of a once-daily oral administration schedule. The indication was locally advanced uterine cervical carcinoma after definitive treatment. An escalating dose (3, 10, and 30 mg/kg per day) of bikunin was administered orally to nine patients for 7 days. There were no dose-limiting toxicities and the MTD of the bikunin schedule was not defined. The authors also obtained preliminary data on its effect on urokinase-type plasminogen activator expression at the highest dose level. CONCLUSIONS: Once-daily oral administration of bikunin was found to be safe in humans and exhibited signs of biologic activity. Copyright 2004 American Cancer Society.",
"title": "Therapeutic efficacy of once-daily oral administration of a Kunitz-type protease inhibitor, bikunin, in a mouse model and in human cancer."
},
{
"docid": "MED-1226",
"text": "Background Several components of dairy products have been linked to earlier menarche. Methods/Findings This study assessed whether positive associations exist between childhood milk consumption and age at menarche or the likelihood of early menarche (<12 yrs) in a U.S sample. Data derive from the National Health and Nutrition Examination Survey (NHANES) 1999–2004. Two samples were utilized: 2657 women age 20–49 yrs and 1008 girls age 9–12 yrs. In regression analysis, a weak negative relationship was found between frequency of milk consumption at 5–12 yrs and age at menarche (daily milk intake β = −0.32, P<0.10; “sometimes/variable milk intake” β = −0.38, P<0.06, each compared to intake rarely/never). Cox regression yielded no greater risk of early menarche among those who drank milk “sometimes/varied” or daily vs. never/rarely (HR: 1.20, P<0.42, HR: 1.25, P<0.23, respectively). Among the 9–12 yr olds, Cox regression indicated that neither total dairy kcal, calcium and protein, nor daily milk intake in the past 30 days contributed to early menarche. Girls in the middle tertile of milk intake had a marginally lower risk of early menarche than those in the highest tertile (HR: 0.6, P<0.06). Those in the lowest tertiles of dairy fat intake had a greater risk of early menarche than those in the highest (HR: 1.5, P<0.05, HR: 1.6, P<0.07, lowest and middle tertile, respectively), while those with the lowest calcium intake had a lower risk of early menarche (HR: 0.6, P<0.05) than those in the highest tertile. These relationships remained after adjusting for overweight or overweight and height percentile; both increased the risk of earlier menarche. Blacks were more likely than Whites to reach menarche early (HR: 1.7, P<0.03), but not after controlling for overweight. Conclusions There is some evidence that greater milk intake is associated with an increased risk of early menarche, or a lower age at menarche.",
"title": "Milk Intake and Total Dairy Consumption: Associations with Early Menarche in NHANES 1999-2004"
},
{
"docid": "MED-2290",
"text": "Background Differences in nutrient profiles between vegetarian and non vegetarian dietary patterns reflect nutritional differences that may contribute to the development of disease. Objective To compare nutrient intakes between dietary patterns characterized by consumption or exclusion of meat and dairy products. Design Cross-sectional study of 71751 subjects (mean age 59 years) from the Adventist-Health-Study-2. Data was collected between 2002 and 2007. Participants completed a 204-item validated semi-quantitative food frequency questionnaire. Dietary patterns compared were: non vegetarian, semi vegetarian, pesco vegetarian, lacto-ovo vegetarian and strict vegetarian. ANCOVA was used to analyze differences in nutrient intakes by dietary patterns and were adjusted for age, and sex and race. BMI and other relevant demographic data were reported and compared by dietary pattern using chi-square tests and ANOVA. Results Many nutrient intakes varied significantly between dietary patterns. Non vegetarians had the lowest intakes of plant proteins, fiber, β-Carotene, and Mg than those following vegetarian dietary patterns and the highest intakes of saturated, trans, arachidonic, and docosahexaenoic fatty acids. The lower tails of some nutrient distributions in strict vegetarians suggested inadequate intakes by a portion of the subjects. Energy intake was similar among dietary patterns at close to 2000 kcal/d with the exception of semi vegetarians that had an intake of 1713 kcal/d. Mean BMI was highest in non-vegetarians (mean; standard deviation [SD]) (28.7; [6.4]) and lowest in strict vegetarians (24.0; [4.8]). Conclusions Nutrient profiles varied markedly between dietary patterns that were defined by meat and dairy intakes. These differences can be of interest in the etiology of obesity and chronic diseases.",
"title": "Nutrient Profiles of Vegetarian and Non Vegetarian Dietary Patterns"
},
{
"docid": "MED-1722",
"text": "Overexpression of growth factors and/or their receptors is a common event in malignancy and provides the underlying mechanisms for one of the hallmarks of cancer, uncontrolled proliferation. Mounting evidence suggests that IGF-1 is involved in the pathogenesis and progression of different types of human cancer such as colon, breast, prostate and lung. However, only a few studies have investigated the association between IGF-1 levels and childhood cancer risk. We aimed to compare the IGF-1 serum level in children with de novo malignancies to healthy children, and to assess its relationship with cancer type, stage, metastasis and different disease characteristics. The study was carried out on 100 children; 50 children with de novo malignancies and 50 healthy children of matched age and gender as a control group. The patients were subjected to a routine work-up for their cancers according to our local standards. Estimation of the serum level of IGF-1 was carried out in the two groups using ELISA. Our results showed that children with cancer had significantly higher levels of IGF-1 than healthy controls of the same age and gender. No association was found between IGF-1 and tumor type, stage, metastasis and other disease characteristics. In conclusion, the IGF-1 serum level is an important indicator of risk for the most prevalent forms of childhood cancer. It may be used to identify children at the highest risk for these cancers and aid in determing who may benefit most from preventive strategies. Given the small number of children in our study, studies with larger populations are required to confirm these results.",
"title": "Insulin-like growth factor-1 and childhood cancer risk"
},
{
"docid": "MED-2649",
"text": "Background Dietary fat exerts numerous complex effects on proinflammatory and immunologic pathways. Several epidemiological studies have examined the relationships between intake of fatty acids and/or foods high in fat and allergic rhinitis, but have provided conflicting findings. The current cross-sectional study investigated such relationships in Japan. Methods Study subjects were 1745 pregnant women. The definition of rhinoconjunctivitis was based on criteria from the International Study of Asthma and Allergies in Childhood. Information on dietary factors was collected using a validated self-administered diet history questionnaire. Adjustment was made for age; gestation; region of residence; number of older siblings; number of children; smoking; secondhand smoke exposure at home and at work; family history of asthma, atopic eczema, and allergic rhinitis; household income; education; and body mass index. Results The prevalence of rhinoconjunctivitis in the past 12 months was 25.9%. Higher meat intake was significantly associated with an increased prevalence of rhinoconjunctivitis: the adjusted odds ratio between extreme quartiles was 1.71 (95% confidence interval: 1.25-2.35, P for trend = 0.002). No measurable association was found between fish intake and rhinoconjunctivitis. Intake of total fat, saturated fatty acids, monounsaturated fatty acids, n-3 polyunsaturated fatty acids, α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, n-6 polyunsaturated fatty acids, linoleic acid, arachidonic acid, and cholesterol and the ratio of n-3 to n-6 polyunsaturated fatty acid intake were not evidently related to the prevalence of rhinoconjunctivitis. Conclusions The current results suggest that meat intake may be positively associated with the prevalence of rhinoconjunctivitis in young adult Japanese women.",
"title": "Dietary meat and fat intake and prevalence of rhinoconjunctivitis in pregnant Japanese women: baseline data from the Kyushu Okinawa Maternal and Child Health Study"
},
{
"docid": "MED-2646",
"text": "BACKGROUND: Certain foods may increase or decrease the risk of developing asthma, rhinoconjunctivitis and eczema. We explored the impact of the intake of types of food on these diseases in Phase Three of the International Study of Asthma and Allergies in Childhood. METHODS: Written questionnaires on the symptom prevalence of asthma, rhinoconjunctivitis and eczema and types and frequency of food intake over the past 12 months were completed by 13-14-year-old adolescents and by the parents/guardians of 6-7-year-old children. Prevalence ORs were estimated using logistic regression, adjusting for confounders, and using a random (mixed) effects model. RESULTS: For adolescents and children, a potential protective effect on severe asthma was associated with consumption of fruit ≥3 times per week (OR 0.89, 95% CI 0.82 to 0.97; OR 0.86, 95% CI 0.76 to 0.97, respectively). An increased risk of severe asthma in adolescents and children was associated with the consumption of fast food ≥3 times per week (OR 1.39, 95% CI 1.30 to 1.49; OR 1.27, 95% CI 1.13 to 1.42, respectively), as well as an increased risk of severe rhinoconjunctivitis and severe eczema. Similar patterns for both ages were observed for regional analyses, and were consistent with gender and affluence categories and with current symptoms of all three conditions. CONCLUSIONS: If the association between fast foods and the symptom prevalence of asthma, rhinoconjunctivitis and eczema is causal, then the findings have major public health significance owing to the rising consumption of fast foods globally.",
"title": "Do fast foods cause asthma, rhinoconjunctivitis and eczema? Global findings from the International Study of Asthma and Allergies in Childhood (ISAA..."
},
{
"docid": "MED-1610",
"text": "The effects of three different meat-containing breakfast meals (pork, beef or chicken) on acute satiety and appetite regulatory hormones were compared using a within-subjects study design. Thirty fasting non-smoking pre-menopausal women attended a research centre on three test days to consume, a meat-containing meal matched in energy (kJ) and protein content, palatability, and appearance. No difference was found between meat groups for either energy intake or macronutrient profile of food consumed at a subsequent ad libitum buffet lunch, or over the rest of the day. Visual Analogue Scale (VAS) ratings for hunger and satiety over an 180 min period did not differ between test meals. After consumption of the test meals, a significant difference was found in PYY response between pork and chicken meals (P=0.027) but not for levels of CCK, ghrelin, insulin or glucose. This study positions pork, beef, and chicken as equal in their effect on satiety and release of appetite-related intestinal hormones and of insulin. Copyright © 2010 Elsevier Ltd. All rights reserved.",
"title": "Pork, beef and chicken have similar effects on acute satiety and hormonal markers of appetite."
},
{
"docid": "MED-3464",
"text": "The purpose of this study was to determine the effects of consuming sweet cherries on plasma lipids and markers of inflammation in healthy humans. Healthy men and women (n = 18) supplemented their diets with Bing sweet cherries (280 g/d) for 28 d. After a 12-h fast, blood samples were taken before the start of cherry consumption (study d 0 and 7), 14 and 28 d after the start of cherry supplementation (study d 21 and 35), and 28 d after the discontinuation (study d 64) of cherry consumption. After cherries were consumed for 28 d, circulating concentrations of C-reactive protein (CRP), regulated upon activation, normal T-cell expressed, and secreted (RANTES), and NO decreased by 25 (P < 0.05), 21 (P < 0.05), and 18% (P = 0.07) respectively. After the discontinuation of cherry consumption for 28 d (d 64), concentrations of RANTES continued to decrease (P = 0.001), whereas those of CRP and NO did not differ from either d 7 (pre-cherries) or d 35 (post-cherries). Plasma concentrations of IL-6 and its soluble receptor, intercellular adhesion molecule-1, and tissue inhibitor of metalloproteinases-2 did not change during the study. Cherry consumption did not affect the plasma concentrations of total-, HDL-, LDL-, and VLDL- cholesterol, triglycerides, subfractions of HDL, LDL, VLDL, and their particle sizes and numbers. It also did not affect fasting blood glucose or insulin concentrations or a number of other chemical and hematological variables. Results of the present study suggest a selective modulatory effect of sweet cherries on CRP, NO, and RANTES. Such anti-inflammatory effects may be beneficial for the management and prevention of inflammatory diseases.",
"title": "Consumption of Bing sweet cherries lowers circulating concentrations of inflammation markers in healthy men and women."
},
{
"docid": "MED-2362",
"text": "The study of the expression of Gal alpha 1----3Gal beta 1----4GlcNAc residues on mammalian glycoconjugates is of particular interest since as many as 1% of circulating IgG antibodies in man (the natural anti-Gal antibody) interact specifically with this carbohydrate residue. In recent studies, we have found that Gal alpha 1----3Gal beta 1----4GlcNAc residues are abundant on red cells and nucleated cells of nonprimate mammals, prosimians, and New World monkeys, but their expression is diminished in Old World monkeys, apes, and humans. In the present work, we have analyzed the expression of these residues on secreted mammalian glycoproteins. For this purpose, we have developed a radioimmunoassay (RIA) which enables the quantification of Gal alpha 1----3Gal beta 1----4GlcNAc residues on the secreted glycoproteins. Purified biotinylated anti-Gal was used as the antibody in the RIA, and bovine thyroglobulin enriched for Gal alpha 1----3Gal beta 1----4GlcNAc residues served as a solid-phase antigen. In this study, it is reported for the first time that the evolutionary pattern of Gal alpha 1----3Gal beta 1----4GlcNAc residue distribution in in vivo secreted glycoproteins is similar to that observed in membranes of cell lines and of red cells. Thyroglobulin, fibrinogen, or IgG molecules from nonprimate mammals and from New World monkeys express varying amounts of Gal alpha 1----3Gal beta 1----4GlcNAc residues ranging between 0.01 and 11 residues per molecule, whereas no such residues are present on any of these glycoproteins of human or Old World monkey origin.(ABSTRACT TRUNCATED AT 250 WORDS)",
"title": "Distribution of Gal alpha 1----3Gal beta 1----4GlcNAc residues on secreted mammalian glycoproteins (thyroglobulin, fibrinogen, and immunoglobulin G..."
},
{
"docid": "MED-3149",
"text": "Many health conditions are treated, at least in part, by therapeutic diets. Although the success of any intervention depends on its acceptability to the patient, the acceptability of therapeutic diets and factors that influence it have been largely neglected in nutrition research. A working definition of acceptability is proposed and an examination and summary are provided of available data on the acceptability of common diet regimens used for medical conditions. The goal is to suggest ways to improve the success of therapeutic diets. The proposed working definition of \"acceptability\" refers to the user's judgment of the advantages and disadvantages of a therapeutic diet-in relation to palatability, costs, and effects on eating behaviour and health-that influence the likelihood of adherence. Very low-calorie, reduced-fat omnivorous, vegetarian and vegan, and low-carbohydrate diets all achieve acceptability among the majority of users in studies of up to one year, in terms of attrition and adherence rates and results of questionnaires assessing eating behaviours. Longer studies are fewer, but they suggest that vegetarian, vegan, and reduced-fat diets are acceptable, as indicated by sustained changes in nutrient intake. Few studies of this length have been published for very low-calorie or low-carbohydrate diets. Long-term studies of adherence and acceptability of these and other therapeutic diets are warranted.",
"title": "Four therapeutic diets: adherence and acceptability."
},
{
"docid": "MED-3774",
"text": "While dehydration has well-documented negative effects on adult cognition, there is little research on hydration and cognitive performance in children. We investigated whether having a drink of water improved children's performance on cognitive tasks. Fifty-eight children aged 7-9 years old were randomly allocated to a group that received additional water or a group that did not. Results showed that children who drank additional water rated themselves as significantly less thirsty than the comparison group (p=0.002), and they performed better on visual attention tasks (letter cancellation, p=0.02; spot the difference memory tasks, ps=0.019 and 0.014).",
"title": "Should children drink more water?: the effects of drinking water on cognition in children."
},
{
"docid": "MED-2763",
"text": "Despite compelling statistics that show we could eliminate 80%of all heart disease and strokes, 90% of all diabetes, and 60% of all cancers with basic lifestyle changes, we have failed to motivate the public to make these changes and failed to motivate policy makers to make healthy choices the easiest choice. Dr. Katz suggests we have failed because we have focused too much on statistics and too little on passion. He implores all of us to tap into people's passion by connecting each of these statistics with a human story.",
"title": "Facing the facelessness of public health: what's the public got to do with it?"
},
{
"docid": "MED-2291",
"text": "PURPOSE: This review focuses on the health benefits of viscous versus nonviscous soluble fibers, why symptoms can occur with increased fiber consumption, and how to avoid symptoms to improve adherence with a high-fiber diet. DATA SOURCES: Review of scientific literature as well as evidence-based guidelines and resources. CONCLUSIONS: While it is generally known that \"fiber is good for you,\" it is less well known that specific health benefits are associated with specific fiber characteristics. Many of the health benefits of fiber can be directly correlated with the viscosity of soluble fibers when hydrated (i.e., gel-forming). A reduction in viscosity of a given fiber will attenuate these health benefits, and a nonviscous fiber does not exhibit these health benefits. IMPLICATIONS FOR PRACTICE: Increasing the viscosity of chyme with a viscous soluble fiber has been shown clinically to lower cholesterol for cardiovascular health, improve glycemic control in type 2 diabetes, normalize stool form in both constipation (softens hard stool) and diarrhea (firms loose/liquid stool), and improve the objective clinical measures of metabolic syndrome (glycemic control, lipoprotein profile, body mass index/weight loss, and blood pressure). ©2012 The Author(s) Journal compilation ©2012 American Academy of Nurse Practitioners.",
"title": "Viscous versus nonviscous soluble fiber supplements: mechanisms and evidence for fiber-specific health benefits."
},
{
"docid": "MED-3457",
"text": "Reactive oxygen species produced during vigorous exercise may permeate into cell nuclei and induce oxidative DNA damage, but the supporting evidence is still lacking. By using a 42 km marathon race as a model of massive aerobic exercise, we demonstrated a significant degree of unrepaired DNA base oxidation in peripheral immunocompetent cells, despite a concurrent increase in the urinary excretion of 8-hydroxy-2'-deoxyguanosine. Single cell gel electrophoresis with the incorporation of lesion-specific endonucleases further revealed that oxidized pyrimidines (endonuclease III-sensitive sites) contributed to most of the postexercise nucleotide oxidation. The oxidative DNA damage correlated significantly with plasma levels of creatinine kinase and lipid peroxidation metabolites, and lasted for more than 1 week following the race. This phenomenon may be one of the mechanisms behind the immune dysfunctions after exhaustive exercise.",
"title": "Oxidative DNA damage in human peripheral leukocytes induced by massive aerobic exercise."
},
{
"docid": "MED-4290",
"text": "BACKGROUND AND AIMS: Nut intake has been inversely related to body mass index (BMI) in prospective studies. We examined dietary determinants of adiposity in an elderly Mediterranean population with customarily high nut consumption. METHODS AND RESULTS: A cross-sectional study was conducted in 847 subjects (56% women, mean age 67 years, BMI 29.7kg/m(2)) at high cardiovascular risk recruited into the PREDIMED study. Food consumption was evaluated by a validated semi-quantitative questionnaire, energy expenditure in physical activity by the Minnesota Leisure Time Activity questionnaire, and anthropometric variables by standard measurements. Nut intake decreased across quintiles of both BMI and waist circumference (P-trend <0.005; both). Alcohol ingestion was inversely related to BMI (P-trend=0.020) and directly to waist (P-trend=0.011), while meat intake was directly associated with waist circumference (P-trend=0.018). In fully adjusted multivariable models, independent dietary associations of BMI were the intake of nuts inversely (P=0.002) and that of meat and meat products directly (P=0.042). For waist circumference, independent dietary associations were intake of nuts (P=0.002) and vegetables (P=0.040), both inversely, and intake of meat and meat products directly (P=0.009). From the regression coefficients, it was predicted that BMI and waist circumference decreased by 0.78kg/m(2) and 2.1cm, respectively, for each serving of 30g of nuts. Results were similar in men and women. CONCLUSION: Nut consumption was inversely associated with adiposity independently of other lifestyle variables. It remains to be explored whether residual confounding related to a healthier lifestyle of nut eaters might in part explain these results. Copyright © 2009 Elsevier B.V. All rights reserved.",
"title": "Cross-sectional association of nut intake with adiposity in a Mediterranean population."
},
{
"docid": "MED-3314",
"text": "OBJECTIVES: Evidence suggests that certain occupations and related exposures may increase the risk of malignant lymphoma. Farming, printing and paper industry, wood processing, meat handling and processing, welding, shoe and leather manufacturing and teaching profession are among the categories that have been implicated in previous studies. The relationship between occupation and malignant lymphoma has been investigated in a large European prospective study. METHODS: We investigated occupational risks for lymphomas in the European Prospective Investigation into Cancer and Nutrition (EPIC). The mean follow-up time for 348,555 subjects was 9 years (SD: 2 years). The analysis was based on 866 and 48 newly diagnosed cases of non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL). These were identified in the EPIC subcohorts with occupational data. Data on 52 occupations were collected through standardised questionnaires. Cox proportional hazard models were used to explore the association between occupation and risk of malignant lymphoma. RESULTS: The following occupations were positively associated with malignant NHL after adjustment for study centre, age, sex, socioeconomic status (SES), smoking and alcohol: butchers (HR=1.53, 95% CI 1.05 to 2.48, including multiple myeloma/plasmacytoma; HR=1.30, 95% CI 1.00 to 2.66, excluding multiple myeloma/plasmacytoma) and car repair workers (HR=1.50, 95% CI 1.01 to 2.00, including multiple myeloma/plasmacytoma; HR=1.51, 95% CI 1.01 to 2.31, excluding multiple myeloma/plasmacytoma). HL was associated with gasoline station occupation (HR=4.59, 95% CI 1.08 to 19.6). CONCLUSION: The findings in this current study of a higher risk of NHL among car repair workers and butchers and a higher risk of HL among gasoline station workers suggest a possible role from occupationally related exposures, such as solvents and zoonotic viruses, as risk factors for malignant lymphoma.",
"title": "Occupation and risk of lymphoma: a multicentre prospective cohort study (EPIC)."
},
{
"docid": "MED-3135",
"text": "Background: Only 5% of all breast cancers are the result of BRCA1/2 mutations. Methylation silencing of tumor suppressor genes is well described in sporadic breast cancer; however, its role in familial breast cancer is not known. Methods: CpG island promoter methylation was tested in the initial random periareolar fine-needle aspiration sample from 109 asymptomatic women at high risk for breast cancer. Promoter methylation targets included RARB (M3 and M4), ESR1, INK4a/ARF, BRCA1, PRA, PRB, RASSF1A, HIN-1, and CRBP1. Results: Although the overall frequency of CpG island promoter methylation events increased with age (P < 0.0001), no specific methylation event was associated with age. In contrast, CpG island methylation of RARB M4 (P = 0.051), INK4a/ARF (P = 0.042), HIN-1 (P = 0.044), and PRA (P = 0.032), as well as the overall frequency of methylation events (P = 0.004), was associated with abnormal Masood cytology. The association between promoter methylation and familial breast cancer was tested in 40 unaffected premenopausal women in our cohort who underwent BRCA1/2 mutation testing. Women with BRCA1/2 mutations had a low frequency of CpG island promoter methylation (15 of 15 women had ≤4 methylation events), whereas women without a mutation showed a high frequency of promoter methylation events (24 of 25 women had 5-8 methylation events; P < 0.0001). Of women with a BRCA1/2 mutation, none showed methylation of HIN-1 and only 1 of 15 women showed CpG island methylation of RARB M4, INK4a/ARF, or PRB promoters. Conclusions: This is the first evidence of CpG island methylation of tumor suppressor gene promoters in non-BRCA1/2 familial breast cancer.",
"title": "CpG Island Tumor Suppressor Promoter Methylation in Non-BRCA-Associated Early Mammary Carcinogenesis"
},
{
"docid": "MED-4559",
"text": "The cardiovascular risk reduction associated with different statins for the prevention of cardiovascular disease and the cardiovascular risk increase associated with excess dietary intake of fat have been quantified. However, these relative risks have never been directly juxtaposed to determine whether an increase in relative risk by 1 activity could be neutralized by an opposing change in relative risk from a second activity. The investigators compared the increase in relative risk for cardiovascular disease associated with the total fat and trans fat content of fast foods against the relative risk decrease provided by daily statin consumption from a meta-analysis of statins in primary prevention of coronary artery disease (7 randomized controlled trials including 42,848 patients). The risk reduction associated with the daily consumption of most statins, with the exception of pravastatin, is more powerful than the risk increase caused by the daily extra fat intake associated with a 7-oz hamburger (Quarter Pounder) with cheese and a small milkshake. In conclusion, statin therapy can neutralize the cardiovascular risk caused by harmful diet choices. In other spheres of human activity, individuals choosing risky pursuits (motorcycling, smoking, driving) are advised or compelled to use measures to minimize the risk (safety equipment, filters, seatbelts). Likewise, some individuals eat unhealthily. Routine accessibility of statins in establishments providing unhealthy food might be a rational modern means to offset the cardiovascular risk. Fast food outlets already offer free condiments to supplement meals. A free statin-containing accompaniment would offer cardiovascular benefits, opposite to the effects of equally available salt, sugar, and high-fat condiments. Although no substitute for systematic lifestyle improvements, including healthy diet, regular exercise, weight loss, and smoking cessation, complimentary statin packets would add, at little cost, 1 positive choice to a panoply of negative ones.",
"title": "Can a statin neutralize the cardiovascular risk of unhealthy dietary choices?"
},
{
"docid": "MED-3348",
"text": "Fruit and vegetable consumption is inadequate among adults in the United States; this contributes to preventable morbidity and mortality. More effective dietary intervention strategies are needed. Recently, interventions that advertise the consequences of behavior for appearance have been successful in modifying sun-exposure habits and tobacco use. Such an approach might also facilitate dietary improvement. Consumption of carotenoid-rich fruit and vegetables positively affects skin color, which influences perceptions of health and attractiveness, and promoting such an effect may motivate target audiences to increase consumption of this important food group. This approach represents a novel direction for the field and is potentially suitable for cost-effective, population-level dissemination through the visual media.",
"title": "Appealing to Vanity: Could Potential Appearance Improvement Motivate Fruit and Vegetable Consumption?"
},
{
"docid": "MED-2336",
"text": "Accumulated evidence shows that some phytochemicals provide beneficial effects for human health. Recently, a number of mechanistic studies have revealed that direct interactions between phytochemicals and functional proteins play significant roles in exhibiting their bioactivities. However, their binding selectivities to biological molecules are considered to be lower due to their small and simple structures. In this study, we found that zerumbone, a bioactive sesquiterpene, binds to numerous proteins with little selectivity. Similar to heat-denatured proteins, zerumbone-modified proteins were recognized by heat shock protein 90, a constitutive molecular chaperone, leading to heat shock factor 1-dependent heat shock protein induction in hepa1c1c7 mouse hepatoma cells. Furthermore, oral administration of this phytochemical up-regulated heat shock protein expressions in the livers of Sprague-Dawley rats. Interestingly, pretreatment with zerumbone conferred a thermoresistant phenotype to hepa1c1c7 cells as well as to the nematode Caenorhabditis elegans. It is also important to note that several phytochemicals with higher hydrophobicity or electrophilicity, including phenethyl isothiocyanate and curcumin, markedly induced heat shock proteins, whereas most of the tested nutrients did not. These results suggest that non-specific protein modifications by xenobiotic phytochemicals cause mild proteostress, thereby inducing heat shock response and leading to potentiation of protein quality control systems. We considered these bioactivities to be xenohormesis, an adaptation mechanism against xenobiotic chemical stresses. Heat shock response by phytochemicals may be a fundamental mechanism underlying their various bioactivities.",
"title": "Non-Specific Protein Modifications by a Phytochemical Induce Heat Shock Response for Self-Defense"
},
{
"docid": "MED-4920",
"text": "BACKGROUND: Celiac disease (CD) is an immune-mediated enteropathic condition triggered in genetically susceptible individuals by the ingestion of gluten. Although common in Europe, CD is thought to be rare in the United States, where there are no large epidemiologic studies of its prevalence. The aim of this study was to determine the prevalence of CD in at-risk and not-at-risk groups in the United States. METHODS: Serum antigliadin antibodies and anti-endomysial antibodies (EMA) were measured. In EMA-positive subjects, human tissue transglutaminase IgA antibodies and CD-associated human leukocyte antigen DQ2/DQ8 haplotypes were determined. Intestinal biopsy was recommended and performed whenever possible for all EMA-positive subjects. A total of 13 145 subjects were screened: 4508 first-degree and 1275 second-degree relatives of patients with biopsy-proven CD, 3236 symptomatic patients (with either gastrointestinal symptoms or a disorder associated with CD), and 4126 not-at-risk individuals. RESULTS: In at-risk groups, the prevalence of CD was 1:22 in first-degree relatives, 1:39 in second-degree relatives, and 1:56 in symptomatic patients. The overall prevalence of CD in not-at-risk groups was 1:133. All the EMA-positive subjects who underwent intestinal biopsy had lesions consistent with CD. CONCLUSIONS: Our results suggest that CD occurs frequently not only in patients with gastrointestinal symptoms, but also in first- and second-degree relatives and patients with numerous common disorders even in the absence of gastrointestinal symptoms. The prevalence of CD in symptomatic patients and not-at-risk subjects was similar to that reported in Europe. Celiac disease appears to be a more common but neglected disorder than has generally been recognized in the United States.",
"title": "Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: a large multicenter study."
},
{
"docid": "MED-1719",
"text": "OBJECTIVE: Overexpression of IGF-I occurs in tumors diagnosed in childhood (osteosarcoma, Wilms tumor, neuroblastoma, etc.) and in adults (breast, ovaries, colon and prostate cancer). The aim of our study was to establish the prevalence of malignancies in states of congenital IGF-I deficiency. SUBJECTS: We surveyed 222 patients with congenital IGF-I deficiency (Laron syndrome, GH gene deletion, GHRH receptor defects and IGF-I resistance) and 338 first and second-degree relatives. RESULTS: None of the IGF-I deficient patients had cancer, whereas 9-24% of the family members had a history of malignancy. CONCLUSIONS: Congenital IGF-I deficiency acts as a protecting factor for the development of cancer.",
"title": "Patients with congenital deficiency of IGF-I seem protected from the development of malignancies: a preliminary report."
},
{
"docid": "MED-1613",
"text": "The present study was designed to examine the effects of habitual consumption of Taiwanese vegetarian diets on hormonal secretion, and on lipid and glycaemic control. Of the ninety-eight healthy female adults recruited from Hualien, Taiwan (aged 31-45 years), forty-nine were Buddhist lactovegetarians and forty-nine were omnivores. Dietary intakes were measured, and blood levels of nutrients and hormones were analysed. Vegetarians consumed less energy, fat and protein, but more fibre than the omnivores. Compared with the omnivores, the vegetarians had, on average, lower BMI and smaller waist circumference. Except for slightly lower levels of thyroxine (T4) in vegetarians, vegetarians and omnivores both showed similar levels of triiodothyronine (T3), free T4, thyroid-stimulating hormone, T3:T4 ratio and cortisol. Compared with the omnivores, the vegetarians had significantly lower levels of fasting insulin (median: 35.3 v. 50.6 pmol/l) and plasma glucose (mean: 4.7 (se 0.05) v. 4.9 (se 0.05) mmol/l). Insulin resistance, as calculated by the homeostasis model assessment method, was significantly lower in the vegetarians than in the omnivores (median: 1.10 v. 1.56), while beta-cell function was not different between the two groups. BMI and diet were both independent predictors for insulin resistance, and contributed 18 and 15 % of the variation in insulin resistance, respectively. In conclusion, Taiwanese vegetarians had lower glucose and insulin levels and higher insulin sensitivity than did the omnivores. Diet and lower BMI were partially responsible for the high insulin sensitivity observed in young Taiwanese vegetarians.",
"title": "Taiwanese vegetarians have higher insulin sensitivity than omnivores."
},
{
"docid": "MED-1185",
"text": "Endogenous sulfite is generated as a consequence of the body's normal processing of sulfur-containing amino acids. Sulfites occur as a consequence of fermentation and also occur naturally in a number of foods and beverages. As food additives, sulfiting agents were first used in 1664 and approved in the United States as long ago as the 1800s. With such long experience with their use, it is easy to understand why these substances have been regarded as safe. They are currently used for a variety of preservative properties, including controlling microbial growth, preventing browning and spoilage, and bleaching some foods. It is estimated that up to 500,000 (< .05% of the population) sulfite-sensitive individuals live in the United States. Sulfite sensitivity occurs most often in asthmatic adults--predominantly women; it is uncommonly reported in preschool children. Adverse reactions to sulfites in nonasthmatics are extremely rare. Asthmatics who are steroid-dependent or who have a higher degree of airway hyperreactivity may be at greater risk of experiencing a reaction to sulfite-containing foods. Even within this limited population, sulfite sensitivity reactions vary widely, ranging from no reaction to severe. The majority of reactions are mild. These manifestations may include dermatologic, respiratory, or gastrointestinal signs and symptoms. Severe nonspecific signs and symptoms occur less commonly. Broncho-constriction is the most common sensitivity response in asthmatics. The precise mechanisms of the sensitivity responses have not been completely elucidated. Inhalation of sulfur dioxide (SO2) generated in the stomach following ingestion of sulfite-containing foods or beverages, a deficiency in a mitochondrial enzyme, and an IgE-mediated immune response have all been implicated.(ABSTRACT TRUNCATED AT 250 WORDS)",
"title": "Sulfite sensitivity: significance in human health."
},
{
"docid": "MED-1614",
"text": "AIM: To compare the insulin sensitivity indices between Chinese vegetarians and omnivores. METHODS: The study included 36 healthy volunteers (vegetarian, n=19; omnivore, n=17) who had normal fasting plasma glucose levels. Each participant completed an insulin suppression test. We compared steady-state plasma glucose (SSPG), fasting insulin, the homeostasis model assessment for insulin sensitivity (HOMA-IR and HOMA %S) and beta-cell function (HOMA %beta) between the groups. We also tested the correlation of SSPG with years on a vegetarian diet. RESULTS: The omnivore subjects were younger than the vegetarians (55.7+/-3.7 vs 58.6+/-3.6 year of age, P=0.022). There was no difference between the two groups in sex, blood pressure, renal function tests and lipid profiles. The omnivores had higher serum uric acid levels than vegetarians (5.25+/-0.84 vs 4.54+/-0.75 mg/dl, P=0.011). The results of the indices were different between omnivores and vegetarians (SSPG (mean+/-s.d.) 105.4+/-10.2 vs 80.3+/-11.3 mg/dl, P<0.001; fasting insulin, 4.06+/-0.77 vs 3.02+/-1.19 microU/ml, P=0.004; HOMA-IR, 6.75+/-1.31 vs 4.78+/-2.07, P=0.002; HOMA %S, 159.2+/-31.7 vs 264.3+/-171.7%, P=0.018) except insulin secretion index, HOMA %beta (65.6+/-18.0 vs 58.6+/-14.8%, P=0.208). We found a clear linear relation between years on a vegetarian diet and SSPG (r=-0.541, P=0.017). CONCLUSIONS: The vegetarians were more insulin sensitive than the omnivore counterparts. The degree of insulin sensitivity appeared to be correlated with years on a vegetarian diet.",
"title": "Insulin sensitivity in Chinese ovo-lactovegetarians compared with omnivores."
},
{
"docid": "MED-3277",
"text": "Methionine dependence is a metabolic defect that occurs in many human tumor cell lines but not normal in unestablished cell strains. Methionine-dependent tumor cell lines are unable to proliferate and arrest in the late S/G2 phase of the cell cycle when methionine is replaced by its immediate precursor homocysteine in the culture medium (MET-HCY+ medium). However, it is not known whether methionine dependence occurs in fresh patient tumors as it does in cell lines. In order to determine whether methionine dependence occurs in fresh patient tumors as well as whether methionine dependence occurs in fresh patient tumors as well as in cell lines we took advantage of the technique of sponge-gel-supported histoculture to grow tumors directly from surgery. We then measured nuclear DNA content by image analysis to determine the cell cycle position in MET-HCY+ compared to MET+HCY- medium in 21 human patient tumors. Human tumor cell lines found to be methionine dependent by cell count were used as positive controls and were found to have marked reduction of cells in G1 compared to total cells in the cell cycle in MET-HCY+ medium with respect to the G1: total cell ratio in MET+HCY- medium. Therefore late cell cycle arrest was used as a marker of methionine dependence for histocultured patient tumors. We found that 5 human tumors of 21, including tumors of the colon, breast, ovary, prostate, and a melanoma, were methionine dependent based on cell cycle analysis. These data on fresh human tumors indicate that methionine dependence may frequently occur in the cancer patient population. Implications for potential therapy based on methionine dependence are discussed.",
"title": "Expression of the biochemical defect of methionine dependence in fresh patient tumors in primary histoculture."
},
{
"docid": "MED-2276",
"text": "A limited number of studies have demonstrated that some modulators of inflammation can be altered by the consumption of sweet cherries. We have taken a proteomics approach to determine the effects of dietary cherries on targeted gene expression. The purpose was then to determine changes caused by cherry consumption in the plasma concentrations of multiple biomarkers for several chronic inflammatory diseases in healthy humans with modestly elevated C-reactive protein (CRP; range, 1-14 mg/L; mean, 3.5 mg/L; normal, <1.0 mg/L). Eighteen men and women (45-61 y) supplemented their diets with Bing sweet cherries (280 g/d) for 28 d. Fasting blood samples were taken before the start of consuming the cherries (study d 7), 28 d after the initiation of cherry supplementation (d 35), and 28 d after the discontinuation (d 63). Of the 89 biomarkers assessed, cherry consumption for 28 d altered concentrations of 9, did not change those of 67, and the other 13 were below the detection limits. Cherry consumption decreased (P < 0.05) plasma concentrations of extracellular newly identified ligand for the receptor for advanced glycation end products (29.0%), CRP (20.1%), ferritin (20.3%), plasminogen activator inhibitor-1 (19.9%), endothelin-1 (13.7%), epidermal growth factor (13.2%), and IL-18 (8.1%) and increased that of IL-1 receptor antagonist (27.9%) compared with corresponding values on study d 7. The ferritin concentration continued to decrease between d 35 and 63 and it was significantly lower on d 63 than on d 7. Because the participants in this study were healthy, no clinical pathology end points were measured. However, results from the present study demonstrate that cherry consumption selectively reduced several biomarkers associated with inflammatory diseases.",
"title": "Sweet bing cherries lower circulating concentrations of markers for chronic inflammatory diseases in healthy humans."
},
{
"docid": "MED-1223",
"text": "OBJECTIVE: To assess the life history consequences of cow milk consumption at different stages in early life (prenatal to adolescence), especially with regard to linear growth and age at menarche and the role of insulin-like growth factor I (IGF-I) in mediating a relationship among milk, growth and development, and long-term biological outcomes. METHODS: United States National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2004 and review of existing literature. RESULTS: The literature tends to support milk's role in enhancing growth early in life (prior to age 5 years), but there is less support for this relationship during middle childhood. Milk has been associated with early menarche and with acceleration of linear growth in adolescence. NHANES data show a positive relationship between milk intake and linear growth in early childhood and adolescence, but not middle childhood, a period of relatively slow growth. IGF-I is a candidate bioactive molecule linking milk consumption to more rapid growth and development, although the mechanism by which it may exert such effects is unknown. CONCLUSIONS: Routine milk consumption is an evolutionarily novel dietary behavior that has the potential to alter human life history parameters, especially vis-à-vis linear growth, which in turn may have negative long-term biological consequences. Copyright © 2011 Wiley Periodicals, Inc.",
"title": "Cow milk consumption, insulin-like growth factor-I, and human biology: a life history approach."
},
{
"docid": "MED-2368",
"text": "BACKGROUND: Microparticles (MPs) with procoagulant activity are present in human atherosclerosis, but no detailed information is available on their composition. METHODS AND RESULTS: To obtain insights into the role of MPs in atherogenesis, MP proteins were identified by tandem mass spectrometry, metabolite profiles were determined by high-resolution nuclear magnetic resonance spectroscopy, and antibody reactivity was assessed against combinatorial antigen libraries. Plaque MPs expressed surface antigens consistent with their leukocyte origin, including major histocompatibility complex classes I and II, and induced a dose-dependent stimulatory effect on T-cell proliferation. Notably, taurine, the most abundant free organic acid in human neutrophils, which scavenges myeloperoxidase-catalyzed free radicals, was highly enriched in plaque MPs. Moreover, fluorescent labeling of proteins on the MP surface suggested immunoglobulins to be trapped inside, which was confirmed by flow cytometry analysis on permeabilized and nonpermeabilized plaque MPs. Colabeling for CD14 and IgG established that more than 90% of the IgG containing MPs were CD14(+), indicating a macrophage origin. Screening against an antigen library revealed that the immunologic profiles of antibodies in MPs were similar to those found in plaques but differed profoundly from antibodies in plasma and unexpectedly, showed strong reactions with oligosaccharide antigens, in particular blood group antigen A. CONCLUSIONS: This study provides the first evidence that immunoglobulins are present within MPs derived from plaque macrophages, that the portfolio of plaque antibodies is different from circulating antibodies in plasma, and that anticarbohydrate antibodies are retained in human atherosclerotic lesions.",
"title": "Proteomics, metabolomics, and immunomics on microparticles derived from human atherosclerotic plaques."
},
{
"docid": "MED-2468",
"text": "BACKGROUND AND METHODS: We estimated the prevalence of self-reported asthma in adult Indians and examined several risk factors influencing disease prevalence. Analysis is based on 99 574 women and 56 742 men aged 20–49 years included in India’s third National Family Health Survey, 2005–2006. Multiple logistic regression analysis was used to estimate the prevalence odds ratios for asthma, adjusting for various risk factors. RESULTS: The prevalence of self-reported asthma was 1.8% (95%CI 1.6–2.0) among men and 1.9% (95%CI 1.8–2.0) among women, with higher rates in rural than in urban areas and marked geographic differences. After adjustment for known asthma risk factors, women were 1.2 times more likely to have asthma than men. Daily/weekly consumption of milk/milk products, green leafy vegetables and fruits were associated with a lower asthma risk, whereas consumption of chicken/meat, a lower body mass index (BMI; <16 kg/m2, OR 2.08, 95%CI 1.73–2.50) as well as a higher BMI (>30 kg/m2, OR 1.67, 95%CI 1.36–2.06), current tobacco smoking (OR 1.30, 95%CI 1.12–1.50) and ever use of alcohol (OR 1.21, 95%CI 1.05–1.39) were associated with an increased asthma risk. CONCLUSIONS: There are wide regional variations in the prevalence of asthma in India. With the exception of the findings for BMI, however, most of the associations of asthma with the risk factors are relatively weak and account for only a small proportion of cases. RÉSUMÉ CONTEXTE ET MÉTHODES: Nous avons estimé la prévalence auto-rapportée de l’asthme chez les Indiens adultes et examiné plusieurs facteurs de risque influençant la prévalence de la maladie. L’analyse repose sur 99 574 femmes et 56 742 hommes âgés de 20 à 49 ans et inclus dans la troisième Enquête Nationale des Familles en Inde, 2005–2006. On a utilisé l’analyse de régression logistique multiple pour estimer les odds ratio de prévalence pour l’asthme, après ajustement pour divers facteurs de risque. RÉSULTATS: La prévalence auto-rapportée de l’asthme est de 1,8% (IC95% 1,6–2,0) parmi les hommes et de 1,9% (IC95% 1,8–2,0) parmi les femmes, les taux étant plus élevés dans les zones rurales que dans les zones urbaines, et les différences géographiques étant marquées. Après ajustement pour les facteurs de risque d’asthme connus, les femmes sont 1,2 fois plus susceptibles de souffrir de l’asthme que les hommes. La consommation quotidienne ou hebdomadaire de lait/produits laitiers, de légumes à feuilles vertes et de fruits est en association avec un risque plus faible d’asthme alors que la consommation de poulet ou de viande, un index de masse corporelle (BMI) plus bas (<16 kg/m2, OR 2,08 ; IC95% 1,73–2,50) ainsi qu’un BMI plus élevé (>30 kg/m2, OR 1,67 ; IC95% 1,36–2,06), le fait de fumer du tabac actuellement (OR 1,30 ; IC95% 1,12–1,50) et l’utilisation de l’alcool à un moment quelconque (OR 1,21 ; IC95% 1,05–1,39) sont en association avec un risque accru d’asthme. La prévalence de l’asthme en Inde varie largement selon les régions. Toutefois, à l’exception des observations sur le BMI, l’association de l’asthme avec les facteurs de risque est relativement faible et ne rend compte que d’une petite proportion des cas seulement. RESUMEN MARCO DE REFERENCIA Y MÉTODOS: Se calculó la prevalencia de asma autorreferida en los adultos en la India y se evaluaron varios factores de riesgo que influyen sobre la prevalencia de la enfermedad. El estudio se basó en las 99 574 mujeres y los 56 742 hombres de 20 a 49 años de edad que participaron en la tercera Encuesta Nacional sobre la Salud de la Familia en la India entre el 2005 y el 2006. Mediante un análisis de regresión logística multifactorial se calculó la prevalencia de asma y el cociente de posibilidades de padecerla, al corregir diversos factores de riesgo. RESULTADOS: La prevalencia de asma autorreferida fue 1,8% en los hombres (intervalo de confianza [IC] del 95% 1,6 a 2,0) y 1,9% en las mujeres (IC95% 1,8 a 2,0); se observaron tasas más altas en las zonas rurales que en las zonas urbanas y se presentaron diferencias geográficas considerables. Tras corregir en función de algunos factores de riesgo de padecer asma conocidos, las mujeres presentaron una probabilidad 1,2 veces superior a los hombres de sufrir la enfermedad. El consumo diario o semanal de leche o productos lácteos, hortalizas de hojas verdes y frutas se asoció con un menor riesgo de asma y el consumo de carne de pollo o de res, un bajo índice de masa corporal (<16 kg/m2; OR 2,08; IC95% 1,73 a 2,50) igual que un alto índice de masa corporal (>30 kg/m2; OR 1,67; IC95% 1,36 a 2,06), el tabaquismo actual (OR 1,30; IC95% 1,12 a 1,50) y el consumo de alcohol en algún momento de la vida (OR 1,21; IC95% 1,05 a 1,39) se asociaron con un mayor riesgo de padecer la enfermedad. CONCLUSIÓN: Existen amplias variaciones geográficas en la prevalencia de asma en la India. Sin embargo, con la excepción del índice de masa corporal, la mayor parte de las asociaciones del asma con los factores de riesgo fueron débiles y explican solo una pequeña proporción de los casos.",
"title": "Prevalence and risk factors for self-reported asthma in an adult Indian population: a cross-sectional survey"
},
{
"docid": "MED-3283",
"text": "Available information indicates that long-lived mammals have low rates of reactive oxygen species (ROS) generation and oxidative damage at their mitochondria. On the other hand, many studies have consistently shown that dietary restriction (DR) in rodents also decreases mitochondrial ROS (mtROS) production and oxidative damage to mitochondrial DNA and proteins. It has been observed that protein restriction also decreases mtROS generation and oxidative stress in rat liver, whereas neither carbohydrate nor lipid restriction change these parameters. This is interesting because protein restriction also increases maximum longevity in rodents (although to a lower extent than DR) and is a much more practicable intervention for humans than DR, whereas neither carbohydrate nor lipid restriction seem to change rodent longevity. Moreover, it has been found that isocaloric methionine restriction also decreases mtROS generation and oxidative stress in rodent tissues, and this manipulation also increases maximum longevity in rats and mice. In addition, excessive dietary methionine also increases mtROS generation in rat liver. These studies suggest that the reduced intake of dietary methionine can be responsible for the decrease in mitochondrial ROS generation and the ensuing oxidative damage that occurs during DR, as well as for part of the increase in maximum longevity induced by this dietary manipulation. In addition, the mean intake of proteins (and thus methionine) of Western human populations is much higher than needed. Therefore, decreasing such levels to the recommended ones has a great potential to lower tissue oxidative stress and to increase healthy life span in humans while avoiding the possible undesirable effects of DR diets.",
"title": "Lowered methionine ingestion as responsible for the decrease in rodent mitochondrial oxidative stress in protein and dietary restriction possible i..."
},
{
"docid": "MED-1250",
"text": "The effect of plant and animal protein on blood lipid levels was investigated in eight healthy normolipidemic men aged 18 to 27 yr. All subjects were fed both plant and animal protein diets in a cross-over design. Each diet was consumed for a 21-day period. Proteins from commonly used plant sources made up the plant protein diet. Beef protein was substituted for 55% of the plant proteins in the animal protein diet. Fasting venous blood samples were collected at the beginning of the study and at 7-day intervals throughout the 42-day study. Serum was analyzed for total cholesterol and triglycerides. Plasma low-density and high-density lipoprotein cholesterol were determined. There were not any statistically significant differences in mean serum total cholesterol or mean plasma low-density lipoprotein cholesterol when subjects consumed the diets. Mean plasma high-density lipoprotein cholesterol levels were significantly (p less than 0.05) elevated at the end of the 21-day period when the animal protein diet was consumed (48 +/- 3 mg/dl) compared to the period when the plant protein diet was fed (42 +/- 2 mg/dl). Mean serum triglyceride values were significantly (p less than 0.05) increased at day 7 of the plant protein diet period (136 +/- 19 mg/dl) compared to the same time period when the animal protein diet was consumed (84 +/- 12 mg/dl). The results of the study indicated that the ingestion of a diet in which 55% of the protein was supplied by beef protein was not associated with a hypercholesterolemic effect in healthy normolipidemic young men.",
"title": "A comparison of the effect of diets containing beef protein and plant proteins on blood lipids of healthy young men."
},
{
"docid": "MED-1229",
"text": "Milk has been recognized to represent a functionally active nutrient system promoting neonatal growth of mammals. Cell growth is regulated by the nutrient-sensitive kinase mechanistic target of rapamycin complex 1 (mTORC1). There is still a lack of information on the mechanisms of mTORC1 up-regulation by milk consumption. This review presents milk as a materno-neonatal relay system functioning by transfer of preferential amino acids, which increase plasma levels of glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), insulin, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) for mTORC1 activation. Importantly, milk exosomes, which regularly contain microRNA-21, most likely represent a genetic transfection system enhancing mTORC1-driven metabolic processes. Whereas human breast milk is the ideal food for infants allowing appropriate postnatal growth and species-specific metabolic programming, persistent high milk signaling during adolescence and adulthood by continued cow´s milk consumption may promote mTORC1-driven diseases of civilization.",
"title": "Milk is not just food but most likely a genetic transfection system activating mTORC1 signaling for postnatal growth"
},
{
"docid": "MED-2472",
"text": "Thirty-five patients who had suffered from bronchial asthma for an average of 12 yr, all receiving long-term medication, 20 including cortisone, were subject to therapy with vegan food for 1 yr. In almost all cases, medication was withdrawn or drastically reduced. There was a significant decrease in asthma symptoms. Twenty-four patients (69%) fulfilled the treatment. Of these, 71% reported improvement at 4 months and 92% at 1 yr. There was a significant improvement in a number of clinical variables; for example, vital capacity, forced expiratory volume at one sec and physical working capacity, as well as a significant change in various biochemical indices as haptoglobin, IgM, IgE, cholesterol, and triglycerides in blood. Selected patients, with a fear of side-effects of medication, who are interested in alternative health care, might get well and replace conventional medication with this regimen.",
"title": "Vegan regimen with reduced medication in the treatment of bronchial asthma."
},
{
"docid": "MED-3311",
"text": "OBJECTIVES: We studied mortality in two separate cohorts of workers in abattoirs (N=4996) and meat processing plants (N=3642) belonging to a meatcutters' union, because they were exposed to viruses that cause cancer in food animals, and also to chemical carcinogens at work. METHODS: Standardized mortality ratios (SMRs) and proportional mortality ratios (PMRs) were estimated for each cohort as a whole and in subgroups defined by race and sex, using the US general population mortality rates for comparison. Study subjects were followed up from January 1950 to December 2006, during which time over 60% of them died. RESULTS: An excess of deaths from cancers of the base of the tongue, esophagus, lung, skin, bone and bladder, lymphoid leukemia, and benign tumors of the thyroid and other endocrine glands, and possibly Hodgkin's disease, was observed in abattoir and meat processing workers. Significantly lower SMRs were recorded for cancer of the thymus, mediastinum, pleura, etc., breast cancer, and non-Hodgkin's lymphoma. CONCLUSION: This study confirms the excess occurrence of cancer in workers in abattoirs and meat processing plants, butchers, and meatcutters, previously reported in this cohort and other similar cohorts worldwide. Large nested case-control studies are now needed to examine which specific occupational and non-occupational exposures are responsible for the excess. There is now sufficient evidence for steps to be taken to protect workers from carcinogenic exposures at the workplace. There are also serious implications for the general population which may also be exposed to some of these viruses. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Cancer mortality in workers employed in cattle, pigs, and sheep slaughtering and processing plants."
},
{
"docid": "MED-2357",
"text": "Patients with cancer have circulating heterophile antibodies that agglutinate animal red cells via recognition of the mammalian cell surface sialic acid N-glycolylneuraminic acid (Neu5Gc), which was long considered an oncofetal antigen in humans. However, humans are genetically deficient in Neu5Gc production and instead metabolically accumulate Neu5Gc from dietary sources, particularly red meats and milk products. Moreover, mice with a human-like defect showed no alternate pathway for Neu5Gc synthesis and even normal humans express anti-Neu5Gc antibodies. We show here that human tumors accumulate Neu5Gc that is covalently attached to multiple classes of glycans. The paradox of human tumor Neu5Gc accumulation in the face of circulating anti-Neu5Gc antibodies was hypothesized to be due to facilitation of tumor progression by the resulting low-grade chronic inflammation. Indeed, murine tumors expressing human-like levels of Neu5Gc show accelerated growth in syngeneic mice with a human-like Neu5Gc deficiency, coincident with the induction of anti-Neu5Gc antibodies and increased infiltration of inflammatory cells. Transfer of polyclonal monospecific syngeneic mouse anti-Neu5Gc serum also enhanced growth of transplanted syngeneic tumors bearing human-like levels of Neu5Gc, with tumors showing evidence for antibody deposition, enhanced angiogenesis and chronic inflammation. These effects were suppressed by a cyclooxygenase-2 inhibitor, a drug type known to reduce human carcinoma risk. Finally, affinity-purified human anti-Neu5Gc antibodies also accelerate growth of Neu5Gc-containing tumors in Neu5Gc-deficient mice. Taken together, the data suggest that the human propensity to develop diet-related carcinomas is contributed to by local chronic inflammation, resulting from interaction of metabolically-accumulated dietary Neu5Gc with circulating anti-Neu5Gc antibodies.",
"title": "Evidence for a human-specific mechanism for diet and antibody-mediated inflammation in carcinoma progression"
},
{
"docid": "MED-3282",
"text": "BACKGROUND AND AIMS: The mechanisms of cancer cell growth and metastasis are still not entirely understood, especially from the viewpoint of chemical reactions in tumours. Glycolytic metabolism is markedly accelerated in cancer cells, causing the accumulation of glucose (a reducing sugar) and methionine (an amino acid), which can non-enzymatically react and form carcinogenic substances. There is speculation that this reaction produces gaseous sulfur-containing compounds in tumour tissue. The aims of this study were to clarify the products in tumour and to investigate their effect on tumour proliferation. METHODS: Products formed in the reaction between glucose and methionine or its metabolites were analysed in vitro using gas chromatography. Flatus samples from patients with colon cancer and exhaled air samples from patients with lung cancer were analysed using near-edge x-ray fine adsorption structure spectroscopy and compared with those from healthy individuals. The tumour proliferation rates of mice into which HT29 human colon cancer cells had been implanted were compared with those of mice in which the cancer cells were surrounded by sodium hyaluronate gel to prevent diffusion of gaseous material into the healthy cells. RESULTS: Gaseous sulfur-containing compounds such as methanethiol and hydrogen sulfide were produced when glucose was allowed to react with methionine or its metabolites homocysteine or cysteine. Near-edge x-ray fine adsorption structure spectroscopy showed that the concentrations of sulfur-containing compounds in the samples of flatus from patients with colon cancer and in the samples of exhaled air from patients with lung cancer were significantly higher than in those from healthy individuals. Animal experiments showed that preventing the diffusion of sulfur-containing compounds had a pronounced antitumour effect. CONCLUSIONS: Gaseous sulfur-containing compounds are the main products in tumours and preventing the diffusion of these compounds reduces the tumour proliferation rate, which suggests the possibility of a new approach to cancer treatment.",
"title": "Generation of gaseous sulfur-containing compounds in tumour tissue and suppression of gas diffusion as an antitumour treatment."
},
{
"docid": "MED-3356",
"text": "OBJECTIVE: This study examined changes in desires to eat high-fat and low-fat foods across an obesity treatment program. The hypotheses under examination were (1) preferences for low-fat foods would increase across time and (2) preferences for high-fat foods would decrease across time. DESIGN: Single-group, prospective examination of desires to eat 48 foods, categorized according to fat content, before and after the 16-week treatment program. SETTING: University clinic, Memphis, Tennessee. PARTICIPANTS: 118 obese (mean weight = 194.4 lbs) women (mean age = 45.24 years) participating in an obesity treatment program. INTERVENTION: A 16-week cognitive-behavioral program for obesity. VARIABLES MEASURED: Desires to eat 48 foods varying in fat content and whether or not participants actually ate these foods. ANALYSIS: Analysis of variance, multiple regression, and paired t tests. RESULTS: The results indicate that during the program, preferences for low-fat foods increased, whereas preferences for high-fat foods decreased. These changes mirrored the changes in consumption of both low-fat and high-fat foods. CONCLUSIONS AND IMPLICATIONS: Within a behavioral economic perspective, the reinforcement value of low-fat foods may increase following a low-fat dietary intervention, whereas the reinforcing properties of high-fat foods may decline. This is desirable as low-fat foods hold many advantages over high-fat foods in terms of weight maintenance.",
"title": "Desire to eat high- and low-fat foods following a low-fat dietary intervention."
},
{
"docid": "MED-2512",
"text": "Ageing is a challenge for any living organism and human longevity is a complex phenotype. With increasing life expectancy, maintaining long-term health, functionality and well-being during ageing has become an essential goal. To increase our understanding of how ageing works, it may be advantageous to analyze the phenotype of centenarians, perhaps one of the best examples of successful ageing. Healthy ageing involves the interaction between genes, the environment, and lifestyle factors, particularly diet. Besides evaluating specific gene-environment interactions in relation to exceptional longevity, it is important to focus attention on modifiable lifestyle factors such as diet and nutrition to achieve extension of health span. Furthermore, a better understanding of human longevity may assist in the design of strategies to extend the duration of optimal human health. In this article we briefly discuss relevant topics on ageing and longevity with particular focus on dietary patterns of centenarians and nutrient-sensing pathways that have a pivotal role in the regulation of life span. Finally, we also discuss the potential role of Nrf2 system in the pro-ageing signaling emphasizing its phytohormetic activation.",
"title": "Extending healthy ageing: nutrient sensitive pathway and centenarian population"
},
{
"docid": "MED-3931",
"text": "Although a plant-based diet can provide some benefits in Parkinson's disease (PD), no study to date has evaluated the effectiveness of a plant-food diet in the management of the disease. In this pilot study, we compared the effect of a plant-food menu (PFD) and of a omnivorous menu on motor performance of 25 PD patients, 12 in the intervention group (PDi) and 13 in the control group (PDc). After 4 weeks, the PDi group showed a significant reduction (Mann-Whitney test) in the Unified Parkinson's Disease Rating Scale, total score (47.67 vs. 74.46, P = 0.008) and sub-score III motor performances (25.42 vs. 46.46, P = 0.001), and the modified Hoehn and Yahr Staging Scale (1.96 vs. 3.15, P = 0.005). These data suggest that PFD may be useful in the management of PD patients by improving their motor performances. Additional studies are needed in order to confirm these preliminary results.",
"title": "Pilot dietary study with normoproteic protein-redistributed plant-food diet and motor performance in patients with Parkinson's disease."
},
{
"docid": "MED-4433",
"text": "BACKGROUND: The role of zoonotic biological agents in human cancer occurrence has been little studied. Humans are commonly exposed to viruses that naturally infect and cause cancer in food animals such as poultry that constitute part of the biological environment. It is not known if these viruses cause cancer in humans. OBJECTIVE: To study cancer mortality in the largest cohort to date, of 20,132 workers in poultry slaughtering and processing plants, a group with the highest human exposures to these viruses. METHODS: Mortality in poultry workers was compared with that in the US general population through the estimation of standardized mortality ratios. RESULTS: Significantly increased risks were observed in the cohort as a whole or in subgroups, for several cancer sites, viz: cancers of the buccal cavity and pharynx; pancreas; trachea/bronchus/lung; brain; cervix; lymphoid leukemia; monocytic leukemia; and tumors of the hemopoietic and lymphatic systems. Elevated SMRs that were not statistically significant were observed for cancers of the liver, nasopharynx, myelofibrosis, and myeloma. New sites observed to be significantly in excess in this study were cancers of the cervix and penis. CONCLUSION: This large study provides evidence that a human group with high exposure to poultry oncogenic viruses has increased risk of dying from several cancers. Other occupational carcinogenic exposures could be of importance in explaining some of the findings, such as fumes from wrapping machines. These findings may have implications for public health amongst persons in the general population who may also be exposed to these viruses. What is needed now are epidemiologic studies that can demonstrate whether the excess of specific cancers can be attributed to specific occupational exposures while adequately controlling for other potential occupational and non-occupational carcinogenic exposures. Copyright 2010 Elsevier Inc. All rights reserved.",
"title": "Cancer mortality in poultry slaughtering/processing plant workers belonging to a union pension fund."
},
{
"docid": "MED-2474",
"text": "This ISAAC Phase Three synthesis provides summarised information on the main findings of the study, regional tables and figures related to the prevalence and severity of current symptoms of asthma, rhinoconjunctivitis and eczema in the main regions of the world. The large number of surveyed children (≈1,200,000), the large number of centres (233) and countries (98) that participated in ISAAC Phase Three makes this study the most comprehensive survey of these diseases ever undertaken. Globally, the prevalence for current asthma, rhinoconjunctivitis and eczema in the 13-14-year age group was 14.1%, 14.6% and 7.3%, respectively. In the 6-7-year age group the prevalence for current asthma, rhinoconjunctivitis and eczema was 11.7%, 8.5% and 7.9%, respectively. The study shows a wide variability in the prevalence and severity of asthma, rhinoconjunctivitis and eczema which occurs not just between regions and countries but between centres in the same country and centres in the same city. This study definitively establishes that the prevalence of those diseases can be very high in non-affluent centres with low socioeconomic conditions. The large variability also suggests a crucial role of local environment characteristics to determine the differences in prevalence between one place and another. Thus, ISAAC Phase Three has provided a large body of epidemiological information on asthma, rhinoconjunctivitis and eczema in childhood from contrasting environments which is expected to yield new clues about the aetiology of those conditions and reasons for their marked global variability. Copyright © 2012 SEICAP. Published by Elsevier Espana. All rights reserved.",
"title": "The International Study of Asthma and Allergies in Childhood (ISAAC) Phase Three: a global synthesis."
},
{
"docid": "MED-2823",
"text": "Curcumin, the yellow pigment from the rhizoma of Curcuma longa, is a widely studied phytochemical which has a variety of biological activities: anti-inflammatory and anti-oxidative. In this review we discuss the biological mechanisms and possible clinical effects of curcumin treatment on cancer therapy, and neurodegenerative diseases such as Alzheimer's Disease, with particular attention to the cell death processes induced by curcumin. Since oxidative stress and inflammation are major determinants of the aging process, we also argue that curcumin can have a more general effect that slows down the rate of aging. Finally, the effects of curcumin can be described as xenohormetic, since it activates a sort of stress response in mammalian cells.",
"title": "Curcumin in Cell Death Processes: A Challenge for CAM of Age-Related Pathologies"
},
{
"docid": "MED-3295",
"text": "Background Few studies have investigated mortality in seafood workers worldwide, and no such study has been conducted in the United States. The objective of this study was to investigate mortality in American seafood workers. Methods The study population was derived from 4 states and consisted of 4116 subjects who worked mainly in seafood processing plants. They were followed up from 1966 to 2003. Standardized mortality ratios (SMRs) and proportional mortality ratios (PMRs) were estimated, using the US general population for comparison. Results About 45% of the cohort was born after 1949. A total of 788 deaths were recorded; 53% of the decedents were female, and 88% were white. The SMRs for stomach cancer and disorders of the thyroid gland in the cohort as a whole were 2.1 (95% confidence interval [CI], 1.1–3.8) and 6.1 (95% CI 1.3–18.0), respectively. The SMRs for breast cancer, and occlusion/stenosis of the pre-cerebral/cerebral arteries in the cohort as a whole were 0.5 (95% CI, 0.3–0.9) and 0.5 (95% CI, 0.2–0.8), respectively. The SMR for ischemic heart disease in white females was 0.8 (95% CI, 0.6–0.9). Conclusions This cohort had excess deaths from stomach cancer and disorders of the thyroid gland, and deficit of deaths from breast cancer, stroke and ischemic heart disease. The significance of these findings is unknown, especially as less than 20% of the cohort were deceased. Nevertheless, the cohort is unique and important, and further follow-up may shed more light on mortality patterns in this occupational group.",
"title": "Cancer and Noncancer Mortality Among American Seafood Workers"
},
{
"docid": "MED-3321",
"text": "Avian leukosis/sarcoma viruses (ALSV) infect and cause cancers in chickens. Poultry workers are exposed to ALSV and other infectious agents in the workplace. This study examines if industrial hygiene assessment of antibody levels in poultry workers can identify risky job tasks at the higher exposure risk to an infectious agent, i.e., ALSV. We compared ALSV antibody levels in poultry workers and control subjects. Occupational and demographical factors were examined for an association with the exposure risk in poultry workers. We found that the antibody levels were significantly higher in poultry workers than in control subjects. Job category and age together were significantly associated with the antibody levels in workers. Certain job tasks were identified with significantly higher antibody levels as compared to others, implying that recommendations should be made to protect workers at these jobs. The findings of this study indicate that the measurement of antibody levels in workers can be useful for industrial hygiene assessment of exposure to infectious agents.",
"title": "Occupational exposure assessment using antibody levels: exposure to avian leukosis/sarcoma viruses in the poultry industry."
},
{
"docid": "MED-3232",
"text": "High dietary acid load (DAL) may be detrimental to bone mineral density (BMD). The objectives of the study were to: 1) evaluate the cross-sectional relation between DAL and BMD; 2) determine whether calcium intake modifies this association. Men (n=1218) and women (n=907) ≥60y were included from the National Health and Nutrition Examination Survey 2005–2008. Nutrient intake from 2–24h recalls was used to calculate net endogenous acid production (NEAP) and potential renal acid load (PRAL) (mEq/d). PRAL was calculated from dietary calcium (PRALdiet) and diet + supplemental calcium (PRALtotal). Tests for linear trend in adjusted mean BMD of the hip and lumbar spine were performed across energy adjusted NEAP and PRAL quartiles. Modification by calcium intake (dietary or total) above or below 800 mg/d was assessed by interaction terms. Overall, mean age was 69 ± 0.3y. Among women, there was no association between NEAP and BMD. PRALdiet was positively associated with proximal femur BMD (p trend=0.04). No associations were observed with PRALtotal at any BMD site (P-range: 0.38–0.82). Among men, no significant associations were observed of BMD with NEAP or PRAL. However, an interaction between PRALdiet and calcium intake was observed with proximal femur BMD (p=0.08). An inverse association between PRALdiet and proximal femur BMD was detected among men <800 mg/d dietary calcium (p=0.02); and no associations ≥800 mg/d (p=0.98). A significant interaction with PRALtotal was not observed. In conclusion, when supplemental calcium is considered, there is no association between DAL and BMD among adults. Men with low dietary calcium showed an inverse relation with PRAL at the proximal femur; in women no interaction was observed. This study highlights the importance of calcium intakes in counteracting the adverse effect of DAL on bone health. Further research should determine the relation between DAL and change in BMD with very low calcium intake.",
"title": "Dietary acid load is associated with lower bone mineral density in men with low intake of dietary calcium"
},
{
"docid": "MED-4198",
"text": "In this study, silkworm moth (Bombyx mori L.) larvae were regarded as an animal protein source for astronauts in the bioregenerative life support system during long-term deep space exploration in the future. They were fed with mulberry and stem lettuce leaves during the first three instars and the last two instars, respectively. In addition, this kind of environmental approach, which utilised inedible biomass of plants to produce animal protein of high quality, can likewise be applied terrestrially to provide food for people living in extreme environments and/or impoverished agro-ecosystems, such as in polar regions, isolated military bases, ships, submarines, etc. Respiration characteristics of the larvae during development under two main physiological conditions, namely eating and not-eating of leaves, were studied. Nutrient compositions of silkworm powder (SP), ground and freeze-dried silkworms on the 3rd day of the 5th instar larvae, including protein, fat, vitamins, minerals and fatty acids, were measured using international standard methods. Silkworms' respiration rates, measured when larvae were eating mulberry leaves, were higher than those of similar larvae that hadn't eaten such leaves. There was a significant difference between silkworms fed on mulberry leaves and those fed on stem lettuce in the 4th and 5th instars (P<0.01). Amounts of CO2 exhaled by the silkworms under the two physiological regimes differed from each other (P<0.01). There was also a significant difference between the amount of O2 inhaled when the insects were under the two physiological statuses (P<0.01). Moreover, silkworms' respiration quotient under the eating regime was larger than when under the not-eating regime. The SP was found to be rich in protein and amino acids in total; 12 essential vitamins, nine minerals and twelve fatty acids were detected. Moreover, 359 kcal could be generated per 100 gram of SP (dry weight).",
"title": "Insect food for astronauts: gas exchange in silkworms fed on mulberry and lettuce and the nutritional value of these insects for human consumption ..."
},
{
"docid": "MED-2446",
"text": "BACKGROUND: Allergic diseases have risen in prevalence over recent decades. The aetiology remains unclear but is likely to be a result of changing lifestyle and/or environment. A reduction in antioxidant intake, consequent to reduced intake of fresh fruits and vegetables, has been suggested as a possible cause. OBJECTIVE: To investigate whether dietary antioxidant intake at age 5 was related to atopy at 5 and 8 years of age amongst children in an unselected birth cohort. METHODS: Children were followed from birth. Parents completed a validated respiratory questionnaire and children were skin prick tested at 5 and 8 years of age. Serum IgE levels were measured at age 5. At age 5, antioxidant intake was assessed using a semi-quantitative food frequency questionnaire (FFQ). A nutrient analysis program computed nutrient intake, and frequency counts of foods high in the antioxidant vitamins A, C and E were assessed. RESULTS: Eight hundred and sixty-one children completed both the respiratory and FFQ. Beta-carotene intake was associated with reduced risk of allergic sensitization at age 5 [0.80 (0.68-0.93)] and 8 [0.81 (0.70-0.94)]. In addition, beta-carotene intake was negatively associated with total IgE levels (P = 0.002). Vitamin E intake was associated with an increased risk of allergic sensitization [1.19 (1.02-1.39)], only at age 5. There was no association between antioxidant intakes and wheeze or eczema. CONCLUSION: Increased beta-carotene intake was associated with a reduced risk of allergic sensitization and lower IgE levels, in 5- and 8-year-old children. Dietary antioxidants may play a role in the development of allergic sensitization.",
"title": "Dietary antioxidant intake, allergic sensitization and allergic diseases in young children."
},
{
"docid": "MED-2201",
"text": "Measuring food prices per gram, rather than per calorie, is one way to make healthful vegetables appear less expensive. However, a better measure of affordability would take the nutrient content of vegetables into account. This study, based on analyses of US Department of Agriculture datasets, aimed to identify which vegetables, including juices and soups, provided the most nutrients per unit cost. Nutrient density was measured using the Nutrient Rich Foods (NRF) index, based on nine nutrients to encourage: protein; fiber; vitamins A, C, and E; calcium; iron; magnesium; and potassium; and on three nutrients to limit: saturated fat, added sugar, and sodium. Food cost in dollars was calculated per 100 g, per 100 kcal, per serving, and per nutrient content. One-way analyses of variance with post hoc tests were used to determine statistical significance. Results showed that tomato juices and tomato soups, dark green leafy and nonleafy vegetables, and deep yellow vegetables, including sweet potatoes, had the highest NRF scores overall. Highest NRF scores per dollar were obtained for sweet potatoes, white potatoes, tomato juices and tomato soups, carrots, and broccoli. Tomato sauces, raw tomatoes, and potato chips were eaten more frequently than were many other vegetables that were both more affordable and more nutrient-rich. These new measures of affordable nutrition can help foodservice and health professionals identify those vegetables that provide the highest nutrient density per unit cost. Processed vegetables, including soups and juices, can contribute to the quality and the affordability of the diet. Copyright © 2013 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.",
"title": "New metrics of affordable nutrition: which vegetables provide most nutrients for least cost?"
},
{
"docid": "MED-3306",
"text": "OBJECTIVES: Occupation as a farmer has been associated with increased risks of haematological cancers in adults. This study aimed to examine whether farm exposures in childhood contribute to these risks, by using parental occupation in farming as a proxy for growing up on a farm. METHODS: New Zealand death records (1998-2003) of persons aged 35-85 were extracted (n=114 289). For 82.3% usual occupation and the occupation of at least one of the parents could be coded (n=94 054). Unconditional logistic regression analyses included 3119 haematological cancer deaths (cases) and 90 935 deaths from other causes (controls). ORs for farming and growing up on a farm were adjusted for each other, year of birth, age at death, socio-economic status, Māori ethnicity, immigration status and sex. RESULTS: Growing up on a livestock farm was positively associated with haematological cancer (OR 1.22, 95% CI 1.05 to 1.41), particularly for poultry farms (OR 2.99, 95% CI 1.44 to 6.21), while growing up on a crop farm was not (OR 0.81, 95% CI 0.64 to 1.03). Crop farming in adulthood was associated with an increased haematological cancer risk (OR 1.49, 95% CI 1.13 to 1.96), while livestock farming was not (OR 0.80, 95% CI 0.63 to 1.00), except for beef cattle farming (OR 2.99, 95% CI 1.28 to 7.00). These results did not change appreciably when different control groups with different causes of death were used. CONCLUSIONS: These results could suggest a role for early life biological exposures in the development of haematological cancers.",
"title": "Farming, growing up on a farm, and haematological cancer mortality."
},
{
"docid": "MED-3231",
"text": "This review looks at the role of an alkaline diet in health. Pubmed was searched looking for articles on pH, potential renal acid loads, bone health, muscle, growth hormone, back pain, vitamin D and chemotherapy. Many books written in the lay literature on the alkaline diet were also reviewed and evaluated in light of the published medical literature. There may be some value in considering an alkaline diet in reducing morbidity and mortality from chronic diseases and further studies are warranted in this area of medicine.",
"title": "The Alkaline Diet: Is There Evidence That an Alkaline pH Diet Benefits Health?"
},
{
"docid": "MED-3452",
"text": "Vitamins have traditionally been considered as food components that are required in the normal diet to prevent deficiencies. However, a newer concept of the function of vitamins in nutrition has taken them beyond simply prevention of deficiency symptoms. This concept considers that many vitamins, when taken in relatively large doses, have important functions beyond preventing deficiencies. Linus Pauling was instrumental in putting forward this concept, particularly for vitamin C. Thus, relatively high intakes of vitamins, and in particular vitamins C and E which are antioxidants, are considered to be healthy for the human population. This may be true in some special situations such as, for instance, the prevention of Alzheimer's disease progression. However, recent epidemiological evidence has not supported the claim that antioxidant vitamins increase well-being and prolong life span. In fact, vitamin supplementation may be even detrimental and reduce life span. A new concept that we would like to put forward is that nutrients up-regulate the endogenous antioxidant defences. This is particularly true in the case of phytoestrogens for example, which bind to oestrogen receptors and eventually up-regulate the expression of antioxidant genes. In this review we discuss the pros and cons of antioxidant vitamin supplementation and also the possibility that the ingestion of some nutrients may be very effective in increasing antioxidant defences by up-regulating the activity of antioxidant enzymes which are normally present in the cell.",
"title": "Fostering antioxidant defences: up-regulation of antioxidant genes or antioxidant supplementation?"
},
{
"docid": "MED-4950",
"text": "Previously used standards for the diagnosis of precocious puberty in girls no longer appear to be appropriate in the USA, in that a significant number of girls are being seen in paediatricians' offices with breast budding before 8 years of age. The timing of menarche, however, has changed little over the past few decades. Early maturing girls are more likely to become obese in adolescence and adulthood than normal or late maturing girls. Early maturing white girls are heavier at the onset of puberty, but this is not the case for African-American girls or boys of either race. Boys and girls with premature pubarche may be more hyperinsulinaemic than normal children, and girls with premature pubarche more likely to develop functional ovarian and adrenal hyperandrogenism. Early menarche is preceded by prepubertal hyperinsulinaemia. It is proposed that pubertal onset, although not necessarily the tempo of puberty, is influenced by hyperinsulinaemia and insulin resistance. If this hypothesis is correct, insulin resistance may be more prevalent in US children than previously recognized. An advance in timing of onset of puberty has not been noted in other countries, although it is likely that this phenomenon may become more prevalent as other countries adopt a more American lifestyle and diet.",
"title": "The pubertal timing controversy in the USA, and a review of possible causative factors for the advance in timing of onset of puberty."
},
{
"docid": "MED-2501",
"text": "Amino acids play fundamental roles in the cell both as the building blocks of new proteins and as metabolic precursors. To adapt to their limitation during periods of protein starvation, multiple adaptive mechanisms have evolved, including a rapid cessation of new protein synthesis, an increase in amino acid biosynthesis and transport, and autophagy. Here, we discuss what we currently know about how amino acid limitation is sensed, and how this sensing might be transmitted to mTORC1 to regulate protein synthesis and autophagy. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Amino acid sensing and regulation of mTORC1."
},
{
"docid": "MED-1097",
"text": "Moses Maimonides (1135-1204), physician and philosopher, was the greatest Jewish thinker of the Middle Ages. Faced with a life of persecution, exile, and tragedy, Maimonides overcame obstacles to become the leading physician in his era, a clinician whose skills were sought across continents. Despite long days caring for patients, Maimonides wrote extensively about both medicine and philosophy. His medical works span all topics of clinical medicine and reflect rational thinking and an understanding of the relationship between mind and body. Well known for his philosophical writings, such as The Guide for the Perplexed, Maimonides codified Jewish law and revolutionized Jewish thinking. This review of his life and achievements provides insight into the world of a remarkable 12th-century physician and may offer valuable lessons for physicians today.",
"title": "Moses Maimonides: medieval physician and scholar."
},
{
"docid": "MED-4722",
"text": "BACKGROUND: There has been a resurgence of interest in the controversial relation between dietary protein and bone health. OBJECTIVE: This article reports on the first systematic review and meta-analysis of the relation between protein and bone health in healthy human adults. DESIGN: The MEDLINE (January 1966 to September 2007) and EMBASE (1974 to July 2008) databases were electronically searched for all relevant studies of healthy adults; studies of calcium excretion or calcium balance were excluded. RESULTS: In cross-sectional surveys, all pooled r values for the relation between protein intake and bone mineral density (BMD) or bone mineral content at the main clinically relevant sites were significant and positive; protein intake explained 1-2% of BMD. A meta-analysis of randomized placebo-controlled trials indicated a significant positive influence of all protein supplementation on lumbar spine BMD but showed no association with relative risk of hip fractures. No significant effects were identified for soy protein or milk basic protein on lumbar spine BMD. CONCLUSIONS: A small positive effect of protein supplementation on lumbar spine BMD in randomized placebo-controlled trials supports the positive association between protein intake and bone health found in cross-sectional surveys. However, these results were not supported by cohort study findings for hip fracture risk. Any effects found were small and had 95% CIs that were close to zero. Therefore, there is a small benefit of protein on bone health, but the benefit may not necessarily translate into reduced fracture risk in the long term.",
"title": "Dietary protein and bone health: a systematic review and meta-analysis."
},
{
"docid": "MED-3272",
"text": "Objective Early detection and early treatment are of vital importance to the successful treatment of various cancers. The development of a novel screening method that is as economical and non-invasive as the faecal occult blood test (FOBT) for early detection of colorectal cancer (CRC) is needed. A study was undertaken using canine scent detection to determine whether odour material can become an effective tool in CRC screening. Design Exhaled breath and watery stool samples were obtained from patients with CRC and from healthy controls prior to colonoscopy. Each test group consisted of one sample from a patient with CRC and four control samples from volunteers without cancer. These five samples were randomly and separately placed into five boxes. A Labrador retriever specially trained in scent detection of cancer and a handler cooperated in the tests. The dog first smelled a standard breath sample from a patient with CRC, then smelled each sample station and sat down in front of the station in which a cancer scent was detected. Results 33 and 37 groups of breath and watery stool samples, respectively, were tested. Among patients with CRC and controls, the sensitivity of canine scent detection of breath samples compared with conventional diagnosis by colonoscopy was 0.91 and the specificity was 0.99. The sensitivity of canine scent detection of stool samples was 0.97 and the specificity was 0.99. The accuracy of canine scent detection was high even for early cancer. Canine scent detection was not confounded by current smoking, benign colorectal disease or inflammatory disease. Conclusions This study shows that a specific cancer scent does indeed exist and that cancer-specific chemical compounds may be circulating throughout the body. These odour materials may become effective tools in CRC screening. In the future, studies designed to identify cancer-specific volatile organic compounds will be important for the development of new methods for early detection of CRC.",
"title": "Colorectal cancer screening with odour material by canine scent detection"
},
{
"docid": "MED-4038",
"text": "We previously reported an association between prenatal exposure to airborne PAH and lower birth weight, birth length and head circumference. The main goal of the present analysis was to assess the possible impact of co-exposure to PAH-containing of barbecued meat consumed during pregnancy on birth outcomes. The birth cohort consisted of 432 pregnant women who gave birth at term (>36 weeks of gestation). Only non-smoking women with singleton pregnancies, 18-35 years of age, and who were free from chronic diseases such as diabetes and hypertension were included in the study. Detailed information on diet over pregnancy was collected through interviews and the measurement of exposure to airborne PAHs was carried out by personal air monitoring during the second trimester of pregnancy. The effect of barbecued meat consumption on birth outcomes (birthweight, length and head circumference at birth) was adjusted in multiple linear regression models for potential confounding factors such as prenatal exposure to airborne PAHs, child’s sex, gestational age, parity, size of mother (maternal prepregnancy weight, weight gain in pregnancy) and prenatal environmental tobacco smoke (ETS). The multivariable regression model showed a significant deficit in birthweight associated with barbecued meat consumption in pregnancy (coeff = −106.0 g; 95%CI: −293.3, −35.8); The effect of exposure to airborne PAHs was about the same magnitude order (coeff. = −164.6 g; 95%CI: −172.3, − 34.7). Combined effect of both sources of exposure amounted to birth weight deficit of 214.3 g (95%CI: −419.0, − 9.6). Regression models performed for birth length and head circumference showed similar trends but the estimated effects were of borderline significance level. As the intake of barbecued meat did not affect the duration of pregnancy, the reduced birthweight could not have been mediated by shortened gestation period. In conclusion, the study results provided epidemiologic evidence that prenatal PAH exposure from diet including grilled meat might be hazardous for fetal development.",
"title": "IMPACT OF BARBECUED MEAT CONSUMED IN PREGNANCY ON BIRTH OUTCOMES ACCOUNTING FOR PERSONAL PRENATAL EXPOSURE TO AIRBORNE POLYCYCLIC AROMATIC HYDROCARBONS. BIRTH COHORT STUDY IN POLAND"
},
{
"docid": "MED-2589",
"text": "BACKGROUND: Determination of the effects of dietary modification and hyperlipidemic medications in the elderly (> sixty-five years of age) patient has not been significantly investigated to date despite knowledge that elevated cholesterol (TC) and triglyceride (TG) levels increase the risk of coronary artery disease (CAD). METHODS: Twenty-seven individuals were placed into one of three treatment groups and longitudinally followed up to examine the effects of diet and hyperlipidemic medications on TC and TG levels. Group 1 (n = 14) received neither dietary nor drug therapy. Group 2 (n = 9) received dietary counseling without concomitant hyperlipidemic medications. Subjects in group 3 (n = 4) underwent dietary instruction for six months and hyperlipidemic medication(s) for eighteen months. RESULTS: Subjects in group 1 demonstrated a statistical increase in TC (P < or = 0.001) during the study. Patients in groups 2 (P < or = 0.001) and 3 (P < or = 0.05) demonstrated statistical improvement in TC reduction during dietary counseling. The effect on TC was blunted in group 3 after dietary counseling was discontinued. Reductions in TG levels were significant (P < or = 0.001) only for patients in group 2. CONCLUSION: Elderly individuals were able to significantly reduce both TC and TG levels by dietary modification alone. Minimal improvement was seen with the addition of hyperlipidemic medications.",
"title": "Treating hyperlipidemia in the elderly."
},
{
"docid": "MED-4211",
"text": "Circulating levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) have each been associated with premenopausal breast cancer risks. We analyzed data from a cross-sectional study of 261 premenopausal Japanese women aged 20-54 yr with adequate nutritional status to evaluate the relationships between concentrations of IGF-1 and IGFBP-3 in serum and dietary intakes of soy, fats and other nutrients. Diet was assessed by a semiquantitative food frequency questionnaire. There was no significant correlation between soy product as well as soy isoflavone intake and serum IGF-1 or IGFBP-3 levels after controlling for age, total energy, percent body fat, and education level. Total fat intake was significantly inversely correlated with serum IGFBP-3 level (r = -0.13, P = 0.04). The correlations of saturated and monounsaturated fats with serum IGFBP-3 were of borderline significance (r = -0.12, P = 0.06 and r = -0.11, P = 0.07, respectively).",
"title": "Dietary soy and fats in relation to serum insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 levels in premenopausal Jap..."
},
{
"docid": "MED-3316",
"text": "BACKGROUND: Between November, 2006, and May, 2008, a subacute neurological syndrome affected workers from two swine abattoirs in Minnesota and Indiana who had occupational exposure to aerosolised porcine brain. We aimed to describe the pathogenic and immunological characteristics of this illness. METHODS: All patients from two abattoirs who presented or were referred to the Mayo Clinic (Rochester, MN, USA) with neurological symptoms were included. We recorded details of exposure to aerosolised brain tissue and did comprehensive neurological, laboratory, neuroimaging, electrophysiological, pathological, and autoimmune serological assessments. Healthy controls were recruited from the community and from workers at the plant in Minnesota. FINDINGS: 24 patients were identified (21 from Minnesota, three from Indiana). The shortest duration from first exposure to symptom onset was 4 weeks. No infectious agent that could trigger disease was identified. All patients developed polyradiculoneuropathy, which was usually sensory predominant and painful. Two patients had initial CNS manifestations: transverse myelitis and meningoencephalitis. Nerve conduction studies localised abnormalities to the most proximal and distal nerve segments. Quantitative sensory and autonomic testing revealed involvement of large and small sensory fibres and sweat fibres. MRI showed prominent abnormalities of roots and ganglia. Nerve biopsies identified mild demyelination, axonal degeneration, and perivascular inflammation. Protein concentrations were high in the CSF of 18 (86%) of 21 patients. Sera from all patients and 29 (34%) of 85 unaffected workplace controls (but none of 178 community controls) had a distinctive neural-reactive IgG; 75% of patients' sera contained an IgG specific to myelin basic protein. Seropositivity correlated directly with exposure risk in patients and controls. 17 patients required immunomodulatory therapies, six improved spontaneously, and one was lost to follow-up after exposure stopped. INTERPRETATION: The neurological disorder described is autoimmune in origin and is related to occupational exposure to multiple aerosolised porcine brain tissue antigens. The pattern of nerve involvement suggests vulnerability of nerve roots and terminals where the blood-nerve barrier is most permeable. FUNDING: Mayo Clinic Foundation; Minnesota Department of Health; Centers for Disease Control and Prevention. Copyright 2010 Elsevier Ltd. All rights reserved.",
"title": "An outbreak of neurological autoimmunity with polyradiculoneuropathy in workers exposed to aerosolised porcine neural tissue: a descriptive study."
},
{
"docid": "MED-2507",
"text": "Increased plasma levels of adiponectin, metformin therapy of diabetes, rapamycin administration in transplant patients, and lifelong consumption of low-protein plant-based diets have all been linked to decreased risk for various cancers. These benefits may be mediated, at least in part, by down-regulated activity of the mTORC1 complex, a key regulator of protein translation. By boosting the effective availability of the translation initiator eIF4E, mTORC1 activity promotes the translation of a number of \"weak\" mRNAs that code for proteins, often up-regulated in cancer, that promote cellular proliferation, invasiveness, and angiogenesis, and that abet cancer promotion and chemoresistance by opposing apoptosis. Measures which inhibit eIF4E activity, either directly or indirectly, may have utility not only for cancer prevention, but also for the treatment of many cancers in which eIF4E drives malignancy. Since eIF4E is overexpressed in many cancers, strategies which target eIF4E directly--some of which are now being assessed clinically--may have the broadest efficacy in this regard. Many of the \"weak\" mRNAs coding for proteins that promote malignant behavior or chemoresistance are regulated transcriptionally by NF-kappaB and/or Stat3, which are active in a high proportion of cancers; thus, regimens concurrently targeting eIF4E, NF-kappaB, and Stat3 may suppress these proteins at both the transcriptional and translational levels, potentially achieving a very marked reduction in their expression. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "mTORC1 activity as a determinant of cancer risk--rationalizing the cancer-preventive effects of adiponectin, metformin, rapamycin, and low-protein ..."
},
{
"docid": "MED-2509",
"text": "DR (dietary restriction), or reduced food intake without malnutrition, is associated with extended longevity, improved metabolic fitness and increased stress resistance in a wide range of organisms. DR is often referred to as calorie restriction, implying that reduced energy intake is responsible for its widespread and evolutionarily conserved benefits. However, recent data indicate dietary amino acid restriction as a key mediator of DR benefits. In fruitflies, an imbalance in essential amino acid intake is thought to underlie longevity benefits of DR. In mammals, reduced dietary protein or essential amino acid intake can extend longevity, improve metabolic fitness and increase stress resistance. In the present paper we review two evolutionarily conserved signal transduction pathways responsible for sensing amino acid levels. The eIF2α (eukaryotic initiation factor 2α) kinase GCN2 (general amino acid control non-derepressible 2) senses the absence of one or more amino acids by virtue of direct binding to uncharged cognate tRNAs. The presence of certain amino acids, such as leucine, permits activation of the master growth regulating kinase TOR (target of rapamycin). These two signal transduction pathways react to amino acid deprivation by inhibiting general protein translation while at the same time increasing translation of specific mRNAs involved in restoring homoeostasis. Together, these pathways may contribute to the regulation of longevity, metabolic fitness and stress resistance.",
"title": "Amino acid sensing in dietary-restriction-mediated longevity: roles of signal-transducing kinases GCN2 and TOR"
},
{
"docid": "MED-2288",
"text": "In recent years there has been considerable interest in the benefits of high-protein diets. This study determined current usual intake of protein in America. Using the most recent data from the National Health and Nutrition Examination Survey, 2003-2004, usual protein intake for Americans aged 2+ years was estimated. Usual protein intake was calculated on a grams per day, grams per kilogram ideal body weight, and a percentage of calories basis. Protein intake averaged 56 +/- 14 g/d in young children, increased to a high of approximately 91 +/- 22 g/d in adults aged 19-30 y, and decreased to approximately 66 +/- 17 g/d in the elderly. The percentage of the male population who consumed less than the estimated average requirement was very low. Our estimates indicated that 7.7% of adolescent females and 7.2-8.6% of older adult women reported consuming protein levels below their estimated average requirement. The median intake of protein on a percentage of calories basis ranged from 13.4% in children aged 4-8 y to 16.0% in men aged 51-70 y. Even the 95th percentile of protein intake did not approach the highest acceptable macronutrient distribution range of 35% for an age/sex group. The highest 95th percentile of protein intake was 20.8% of calories in men aged 51-70 y. Given the demonstrated benefits of higher protein intake on weight management, sarcopenia, and other physiologic functions, efforts should be undertaken to ensure that Americans consume the recommended amount of protein (17-21% of calories as expected from MyPyramid food patterns).",
"title": "Current protein intake in America: analysis of the National Health and Nutrition Examination Survey, 2003-2004."
},
{
"docid": "MED-2645",
"text": "The development of the male reproductive ducts and external genitalia in vertebrates is dependent on elevated androgen concentrations during embryonic development and the period of postnatal growth. We have observed that a population of juvenile alligators living on Lake Apopka exhibit significantly smaller penis size (24% average decrease) and lower plasma concentrations of testosterone (70% lower concentrations) when compared to animals of similar size on Lake Woodruff. In addition to smaller phalli, no relationship exists between plasma testosterone concentrations and penile size in males from Lake Apopka, whereas a positive relationship exists for males from Lake Woodruff. The alligators on Lake Apopka are known to have elevated concentrations of the antiandrogenic DDT breakdown product p.p'-DDE stored in their fat. We suggest a number of hypotheses that could explain the modification in the phenotype of the juvenile male living in Lake Apopka. These modifications in phenotype include a smaller penis size, lower plasma androgen concentrations, and lack of responsiveness of the penis to the plasma androgens present.",
"title": "Reduction in penis size and plasma testosterone concentrations in juvenile alligators living in a contaminated environment."
},
{
"docid": "MED-3956",
"text": "Early onset of puberty may confer adverse health consequences. Thus, modifiable factors influencing the timing of puberty are of public health interest. Childhood overweight as a factor in the earlier onset of menarche has been supported by prospective evidence; nonetheless, its overall contribution may have been overemphasized, since secular trends toward a younger age at menarche have not been a universal finding during the recent obesity epidemic. Current observational studies suggest notable associations between dietary intakes and pubertal timing beyond contributions to an energy imbalance: children with the highest intakes of vegetable protein or animal protein experience pubertal onset up to 7 months later or 7 months earlier, respectively. Furthermore, girls with high isoflavone intakes may experience the onset of breast development and peak height velocity approximately 7-8 months later. These effect sizes are on the order of those observed for potentially neuroactive steroid hormones. Thus, dietary patterns characterized by higher intakes of vegetable protein and isoflavones and lower intakes of animal protein may contribute to a lower risk of breast cancer or a lower total mortality. © 2012 International Life Sciences Institute.",
"title": "Beyond overweight: nutrition as an important lifestyle factor influencing timing of puberty."
},
{
"docid": "MED-3148",
"text": "We examined the resting metabolic rate (RMR) and sympathetic nervous system activity of young male vegetarians (n = 17) and nonvegetarians (n = 40). Subjects were characterized for RMR by indirect calorimetry, norepinephrine kinetics from infusions of tritiated norepinephrine, energy and macronutrient intake from a 3-day food diary, and body composition by underwater weighing. Vegetarians reported a greater relative intake of carbohydrates (62% +/- 5% v 51% +/- 6%, P < .01) and a lower relative intake of fat (25% +/- 5% v 33% +/- 6%, P < .01) than nonvegetarians, whereas no differences were observed in daily energy intake, body composition, or maximal aerobic capacity (VO2max) between groups. Vegetarians exhibited an 11% higher absolute RMR (1.29 +/- 0.15 v 1.16 +/- 0.13 kcal/min, P < .01), a higher plasma concentration of norepinephrine (216 +/- 33 v 165 +/- 18 pg/mL, P < .01), and a greater norepinephrine appearance rate (0.50 +/- 0.08 v 0.36 +/- 0.09 micrograms/min, P < .01) than nonvegetarians. After statistically controlling for differences in relative amounts of carbohydrate and fat in the diet and for norepinephrine concentrations, no significant differences in adjusted RMR between vegetarians and nonvegetarians were noted. These results suggest that the higher RMR observed in young male vegetarians is partially mediated by differences in dietary macronutrient composition and increased sympathetic nervous system activity.",
"title": "Sympathetic nervous system activity and resting metabolic rate in vegetarians."
},
{
"docid": "MED-1615",
"text": "Hyperinsulinemia, hypertension, hypertriglyceridemia and obesity are independent risk factors for coronary artery disease and are often found in the same person. This study investigated the effects of an intensive, 3-week, dietary and exercise program on these risk factors. The group was divided into diabetic patients (non-insulin-dependent diabetes mellitus [NIDDM], n = 13), insulin-resistant persons (n = 29) and those with normal insulin, less than or equal to 10 microU/ml (n = 30). The normal groups had very small but statistically significant decreases in all of the risk factors. The patients with NIDDM had the greatest decreases. Insulin was reduced from 40 +/- 15 to 27 +/- 11 microU/ml, blood pressure from 142 +/- 9/83 +/- 3 to 132 +/- 6/71 +/- 3 mm Hg, triglycerides from 353 +/- 76 to 196 +/- 31 mg/dl and body mass index from 31.1 +/- 4.0 to 29.7 +/- 3.7 kg/m2. Although there was a significant weight loss for the group with NIDDM, resulting in the decrease in body mass index, 8 of 9 patients who were initially overweight were still overweight at the end of the program, and 5 of the 8 were still obese (body mass index greater than 30 kg/m2), indicating that normalization of body weight is not a requisite for a reduction or normalization of other risk factors. Insulin was reduced from 18.2 +/- 1.8 to 11.6 +/- 1.2 microU/ml in the insulin-resistant group, with 17 of the 29 subjects achieving normal fasting insulin (less than 10 microU/ml).(ABSTRACT TRUNCATED AT 250 WORDS)",
"title": "Role of diet and exercise in the management of hyperinsulinemia and associated atherosclerotic risk factors."
},
{
"docid": "MED-3308",
"text": "An occupational health survey conducted in a workshop in which asbestos cement was used showed initial atmospheric asbestos levels ranging from 1.9 to 27.5 fibres per millilitre of air. Radiological changes suggestive of asbestos-related pleural disease were found in 2 workers (2.5%), while 3 (3.8%) had borderline features of asbestosis. The survey confirmed that uncontrolled and hazardous use of asbestos continues in industry despite public awareness of its dangers and the Asbestos Regulations of 1987.",
"title": "Third wave of asbestos-related disease from secondary use of asbestos. A case report from industry."
},
{
"docid": "MED-1224",
"text": "In adults, dietary protein seems to induce weight loss and dairy proteins may be insulinotropic. However, the effect of milk proteins in adolescents is unclear. The objective was to test whether milk and milk proteins reduce body weight, waist circumference, homeostatic model assessment, plasma insulin, and insulin secretion estimated as the plasma C-peptide concentration in overweight adolescents. Overweight adolescents (n = 203) aged 12-15 y with a BMI of 25.4 ± 2.3 kg/m(2) (mean ± SD) were randomized to 1 L/d of skim milk, whey, casein, or water for 12 wk. All milk drinks contained 35 g protein/L. Before randomization, a subgroup of adolescents (n = 32) was studied for 12 wk before the intervention began as a pretest control group. The effects of the milk-based test drinks were compared with baseline (wk 0), the water group, and the pretest control group. Diet and physical activity were registered. Outcomes were BMI-for-age Z-scores (BAZs), waist circumference, plasma insulin, homeostatic model assessment, and plasma C-peptide. We found no change in BAZ in the pretest control and water groups, whereas it was greater at 12 wk in the skim milk, whey, and casein groups compared with baseline and with the water and pretest control groups. The plasma C-peptide concentration increased from baseline to wk 12 in the whey and casein groups and increments were greater than in the pretest control (P < 0.02). There were no significant changes in plasma C-peptide in the skim milk or water group. These data suggest that high intakes of skim milk, whey, and casein increase BAZs in overweight adolescents and that whey and casein increase insulin secretion. Whether the effect on body weight is primary or secondary to the increased insulin secretion remains to be elucidated.",
"title": "Skim milk, whey, and casein increase body weight and whey and casein increase the plasma C-peptide concentration in overweight adolescents."
},
{
"docid": "MED-3288",
"text": "In the fall of 2007, the Minnesota Department of Health was notified of 11 cases of an unexplained neurological illness, all linked to a pork processing plant, Quality Pork Processors, Inc., in Austin, MN. The cluster of workers had been experiencing similar symptoms, including fatigue, pain, numbness, and tingling in their extremities as well as weakness. The symptoms were described as more sensory than motor, and all patients had evidence of polyradiculoneuropathy with signs of nerve root irritation. An epidemiological investigation revealed that the only commonality between cases was their exposure to a pork brain extraction procedure involving compressed air. As relatives of the cases remained asymptomatic and all cultures for known pathogens were negative, the etiology of the syndrome seemed not to be infectious. Clinically, the syndrome was most akin to chronic inflammatory demyelinating polyneuropathy. Laboratory tests corroborated the clinical findings, revealing inflammation of peripheral nerves and nerve roots; however, these cases also had features clinically distinct from chronic inflammatory demyelinating polyneuropathy as well as laboratory testing revealing a novel immunoglobulin G immunostaining pattern. This suggested that the observed inflammation was the result of 1 or more unidentified antigens. This syndrome was ultimately dubbed progressive inflammatory neuropathy and was theorized to be an autoimmune reaction to aerosolized porcine neural tissue. Since the investigation's outset, 18 cases of progressive inflammatory neuropathy have been identified at the Minnesota pork processing plant, with 5 similar cases at an Indiana plant and 1 case at a Nebraskan plant. The plants in which cases have been identified have since stopped the use of compressed air in removing pork brains. All cases have stabilized or improved, with some requiring immunosuppressive and analgesic treatment. The study of progressive inflammatory neuropathy is ongoing, and the details of this investigation highlight the value of epidemiological principles in the identification and containment of outbreaks while researchers attempt to uncover the unique pathophysiology and potential etiology of the illness. Mt Sinai J Med 76:442-447, 2009. (c) 2009 Mount Sinai School of Medicine.",
"title": "Outbreak of progressive inflammatory neuropathy following exposure to aerosolized porcine neural tissue."
},
{
"docid": "MED-5185",
"text": "There is some evidence that dietary factors may modify the risk of squamous cell carcinoma (SCC) of the skin, but the association between food intake and SCC has not been evaluated prospectively. We examined the association between food intake and SCC incidence among 1,056 randomly selected adults living in an Australian sub-tropical community. Measurement-error corrected estimates of intake in 15 food groups were defined from a validated food frequency questionnaire in 1992. Associations with SCC risk were assessed using Poisson and negative binomial regression to the persons affected and tumour counts, respectively, based on incident, histologically confirmed tumours occurring between 1992 and 2002. After multivariable adjustment, none of the food groups was significantly associated with SCC risk. Stratified analysis in participants with a past history of skin cancer showed a decreased risk of SCC tumours for high intakes of green leafy vegetables (RR = 0.45, 95% CI = 0.22-0.91; p for trend = 0.02) and an increased risk for high intake of unmodified dairy products (RR = 2.53, 95% CI: 1.15-5.54; p for trend = 0.03). Food intake was not associated with SCC risk in persons who had no past history of skin cancer. These findings suggest that consumption of green leafy vegetables may help prevent development of subsequent SCCs of the skin among people with previous skin cancer and that consumption of unmodified dairy products, such as whole milk, cheese and yoghurt, may increase SCC risk in susceptible persons. Copyright 2006 Wiley-Liss, Inc.",
"title": "Food intake and risk of squamous cell carcinoma of the skin in a community: the Nambour skin cancer cohort study."
},
{
"docid": "MED-4047",
"text": "The total phenolic contents and antioxidant activities of garlics from California, Oregon, Washington, and New York were determined by Fourier transform infrared (FT-IR) spectroscopy (400-4000 cm(-1)). The total phenolic content was quantified [Folin-Ciocalteu assay (FC)] and three antioxidant activity assays, 2,2-diphenyl-picrylhydrazyl (DPPH) assay, Trolox equivalent antioxidant capacity (TEAC) assay, and ferric reducing antioxidant power (FRAP), were employed for reference measurements. Four independent partial least-squares regression (PLSR) models were constructed with spectra from 25 extracts and their corresponding FC, DPPH, TEAC, and FRAP with values for 20 additional extracts predicted (R > 0.95). The standard errors of calibration and standard error of cross-validation were <1.45 (TEAC), 0.36 (FRAP), and 0.33 μmol Trolox/g FW (DPPH) and 0.55 mg gallic acid/g FW (FC). Cluster and dendrogram analyses could segregate garlic grown at different locations. Hydroxyl and phenolic functional groups most closely correlated with garlic antioxidant activity.",
"title": "Determination of total phenolic content and antioxidant activity of garlic (Allium sativum) and elephant garlic (Allium ampeloprasum) by attenuated..."
},
{
"docid": "MED-3130",
"text": "Although soy phytoestrogens have been postulated to exert a protective effect against breast cancer, the attendant mechanisms, in particular epigenetics underpinnings, have remained elusive. We investigated the putative effects on DNA methylation by two naturally occurring isoflavones, genistein and daidzein, in a study of the BRCA1 and BRCA2 oncosuppressor genes in breast cancer cell lines (MCF-7, MDA-MB 231, and MCF10a). A demethylant agent, the 5-azacytidine, and a methylant, the budesonide, were used as treatment controls. DNA methylation of BRCA1 and BRCA2 was investigated with methylated DNA immunoprecipitation coupled with PCR. In parallel, protein expression was determined by Western blot, immunohistochemistry, and confocal microscopy. Our results suggest that treatment with 18.5 μM Genistein or 78.5 μM Daidzein might reverse DNA hypermethylation and restore the expression of the oncosuppressor genes BRCA1 and BRCA2. 5-Azacitydine also enhanced the reexpression of these genes while budesonide had an opposite effect. To the best of our knowledge, these observations, while requiring replication, provide new evidence on potential epigenetic mechanisms by which genistein and daidzein might contribute to regulation of the BRCA1 and BRCA2. Future studies are warranted on whether the demethylating effect of genistein and daidzein is global or focused on select candidate genes.",
"title": "Can soy phytoestrogens decrease DNA methylation in BRCA1 and BRCA2 oncosuppressor genes in breast cancer?"
},
{
"docid": "MED-2204",
"text": "The initial investigation of the nature of the proteins in the tuber of sweet potato (Ipomoea batatas Lam.) revealed a globulin-designated \"ipomoein,\" which was reported by Jones and Gersdorff, (1931). Later, \"ipomoein\" was renamed \"sporamin\" and was found to be a major storage protein that accounted for over 80% of the total protein in the tuberous root. To date, sporamin has been studied by a series of biochemical and molecular approaches. The first purification of sporamin into two major fractions, A and B, was successfully completed in 1985. Several characteristics of the protein, such as the diversification of the nucleotide sequences in the gene family, the protein structure, the biological functions of storage, defense, inhibitory activity and ROS scavenging, were identified. In the past decade, sporamin was classified as a Kunitz-type trypsin inhibitor, and its insect-resistance capability has been examined in transgenic tobacco and cauliflower plants, indicating the multiple functions of this protein has evolved to facilitate the growth and development of sweet potato. Sporamin is constitutively expressed in the tuberous root and is not normally expressed in the stem or leaves. However, this protein is expressed systemically in response to wounding and other abiotic stresses. These dual expression patterns at the transcriptional level revealed that the complex regulatory mechanism of sporamin was modulated by environmental stresses. The versatile functions of sporamin make this storage protein a good research model to study molecular evolution, regulatory mechanisms and physiological functions in plants. This review summarizes and discusses recent approaches and future perspectives in agricultural biotechnology. Copyright © 2012 Elsevier Inc. All rights reserved.",
"title": "Multiple biological functions of sporamin related to stress tolerance in sweet potato (Ipomoea batatas Lam)."
},
{
"docid": "MED-2657",
"text": "BACKGROUND: Japanese cedar pollinosis, caused by the pollen of the Japanese cedar tree (Cryptomeria japonica), is the commonest seasonal allergic disease in Japan. A number of epidemiological surveys have been reported on Japanese cedar pollinosis, but it has never been assessed systematically or quantitatively. To confirm the increasing prevalence of Japanese cedar pollinosis and related factors, we conducted a meta-regression analysis on population-based surveys in Japan. METHODS: We searched for data from population-based surveys in which serological methods were used to test all participants. Weighted regression of logit-transformed prevalence and sensitization rates were used to evaluate the effects of the year of survey, age, and degree of urbanization. We also analyzed the relationship between prevalence and sensitization rate. RESULTS: Thirty-eight reports with 27 subgroups for prevalence and 134 subgroups for sensitization rate were selected from the literature published in the years between 1986 and 2000. The Japanese cedar pollen sensitization rate was found to be significantly correlated with the year of survey, age, and degree of urbanization (adjusted R(2) = 0.55). The coefficient for the correlation between the prevalence and the sensitization rate revealed a statistically significant correlation (Pearson's r = 0.70, p < 0.001). CONCLUSIONS: The prevalence of Japanese cedar pollinosis among adolescents was predicted to be 28.7% in metropolitan areas and 24.5% in the general population in urban areas in the year 2004, derived from the estimated sensitization rate and the relationship between sensitization rate and prevalence. The prevalence of Japanese cedar pollinosis increased 2.6-fold between 1980 and 2000, and the prevalence differed considerably according to age and degree of urbanization. Copyright (c) 2005 S. Karger AG, Basel",
"title": "Increasing prevalence of Japanese cedar pollinosis: a meta-regression analysis."
},
{
"docid": "MED-3877",
"text": "OBJECTIVES: Dietary factors may influence the prostate and have an impact on prostatic growth and disease. A small number of studies have suggested that flaxseed-supplemented, fat-restricted diets may thwart prostate cancer growth in both animals and humans. Unknown, however, is the potential effect of such a diet on benign prostatic epithelium. METHODS: We undertook a pilot study to explore whether a flaxseed-supplemented, fat-restricted diet affects the proliferation rates in benign epithelium. We also explored the effects on circulating levels of prostate-specific antigen (PSA), total testosterone, and cholesterol. Fifteen men who were scheduled to undergo repeat prostate biopsy were instructed to follow a low-fat (less than 20% kcal), flaxseed-supplemented (30 g/day) diet and were provided with a supply of flaxseed to last throughout the 6-month intervention period. The PSA, total testosterone, and cholesterol levels were determined at baseline and at 6 months of follow-up. Reports from the original and repeat biopsies were compared, and proliferation (MIB-1) rates were quantified in the benign prostatic epithelium. RESULTS: Statistically significant decreases in PSA (8.47 +/- 3.82 to 5.72 +/- 3.16 ng/mL; P = 0.0002) and cholesterol (241.1 +/- 30.8 to 213.3 +/- 51.2 mg/dL; P = 0.012) were observed. No statistically significant change was seen in total testosterone (434.5 +/- 143.6 to 428.3 +/- 92.5 ng/dL). Although 6-month repeat biopsies were not performed in 2 cases because of PSA normalization, of the 13 men who underwent repeat biopsy, the proliferation rates in the benign epithelium decreased significantly from 0.022 +/- 0.027 at baseline to 0.007 +/- 0.014 at 6 months of follow-up (P = 0.0168). CONCLUSIONS: These pilot data suggest that a flaxseed-supplemented, fat-restricted diet may affect the biology of the prostate and associated biomarkers. A randomized controlled trial is needed to determine whether flaxseed supplementation, a low-fat diet, or a combination of the two regimens may be of use in controlling overall prostatic growth.",
"title": "Pilot study to explore effects of low-fat, flaxseed-supplemented diet on proliferation of benign prostatic epithelium and prostate-specific antigen."
},
{
"docid": "MED-5181",
"text": "Recent evidence suggests overall dietary patterns, rather than specific dietary components, may be a better predictor of colorectal adenomas or cancers. Using cluster analysis, we aimed to assess the association between dietary patterns and colorectal adenomas and whether adjusting for total energy consumption prior to creating clusters affects this relation. Data from a case-control study of 725 individuals undergoing a colonoscopy were utilized. Cases (n = 203) had > or =1 adenoma on colonoscopy, and controls (n = 522) were those who had no adenomas. Dietary data were obtained from an FFQ. Daily intake for 18 different food groups was calculated. The values were transformed into Z-scores. Participants were first clustered without energy adjustment, then again based on their consumption per 1000 kcal (4187 kJ). There was no association between dietary patterns and colorectal adenomas without energy adjustment prior to creating dietary clusters, as clusters formed as a by-product of energy consumption. After adjusting for energy consumption, 3 distinct clusters emerged: 1) high fruit-low meat cluster; 2) high vegetable-moderate meat cluster; and 3) high meat cluster. After adjusting for potential confounders, the high vegetable-moderate meat cluster (odds ratio [OR] 2.17: [95% CI] 1.20-3.90) and high meat cluster (OR 1.70: [95% CI] 1.04-2.80) were at significantly increased odds of having had an adenoma compared with the high fruit-low meat cluster. A high-fruit, low-meat diet appears to be protective against colorectal adenomas compared with a dietary pattern of increased vegetable and meat consumption.",
"title": "A diet high in fruits and low in meats reduces the risk of colorectal adenomas."
},
{
"docid": "MED-5183",
"text": "Dietary phytochemical compounds, including isoflavones and isothiocyanates, may inhibit cancer development but have not yet been examined in prospective epidemiologic studies of ovarian cancer. The authors have investigated the association between consumption of these and other nutrients and ovarian cancer risk in a prospective cohort study. Among 97,275 eligible women in the California Teachers Study cohort who completed the baseline dietary assessment in 1995–1996, 280 women developed invasive or borderline ovarian cancer by December 31, 2003. Multivariable Cox proportional hazards regression, with age as the timescale, was used to estimate relative risks and 95% confidence intervals; all statistical tests were two sided. Intake of isoflavones was associated with lower risk of ovarian cancer. Compared with the risk for women who consumed less than 1 mg of total isoflavones per day, the relative risk of ovarian cancer associated with consumption of more than 3 mg/day was 0.56 (95% confidence interval: 0.33, 0.96). Intake of isothiocyanates or foods high in isothiocyanates was not associated with ovarian cancer risk, nor was intake of macronutrients, antioxidant vitamins, or other micronutrients. Although dietary consumption of isoflavones may be associated with decreased ovarian cancer risk, most dietary factors are unlikely to play a major role in ovarian cancer development.",
"title": "Diet and Risk of Ovarian Cancer in the California Teachers Study Cohort"
},
{
"docid": "MED-2464",
"text": "BACKGROUND: In recent decades, children's diet quality has changed and asthma prevalence has increased, although it remains unclear if these events are associated. OBJECTIVE: To examine children's total and component diet quality and asthma and airway hyperresponsiveness (AHR), a proxy for asthma severity. METHODS: Food frequency questionnaires adapted from the Nurses' Health Study and supplemented with foods whose nutrients which have garnered interest of late in relation to asthma were administered. From these data, diet quality scores (total and component), based on the Youth Healthy Eating Index (YHEI adapted) were developed. Asthma assessments were performed by pediatric allergists and classified by atopic status: Allergic asthma (≥1 positive skin prick test to common allergens >3 mm compared to negative control) versus non-allergic asthma (negative skin prick test). AHR was assessed via the Cockcroft technique. Participants included 270 boys (30% with asthma) and 206 girls (33% with asthma) involved in the 1995 Manitoba Prospective Cohort Study nested case-control study. Logistic regression was used to examine associations between diet quality and asthma, and multinomial logistic regression was used to examine associations between diet quality and AHR. RESULTS: Four hundred seventy six children (56.7% boys) were seen at 12.6 ± 0.5 years. Asthma and AHR prevalence were 26.2 and 53.8%, respectively. In fully adjusted models, high vegetable intake was protective against allergic asthma (OR 0.49; 95% CI 0.29-0.84; P < 0.009) and moderate/severe AHR (OR 0.58; 0.37-0.91; P < 0.019). CONCLUSIONS: Vegetable intake is inversely associated with allergic asthma and moderate/severe AHR. Copyright © 2012 Wiley Periodicals, Inc.",
"title": "Low vegetable intake is associated with allergic asthma and moderate-to-severe airway hyperresponsiveness."
},
{
"docid": "MED-4894",
"text": "SUMMARY: This cross-sectional study showed that, although vegans had lower dietary calcium and protein intakes than omnivores, veganism did not have adverse effect on bone mineral density and did not alter body composition. INTRODUCTION: Whether a lifelong vegetarian diet has any negative effect on bone health is a contentious issue. We undertook this study to examine the association between lifelong vegetarian diet and bone mineral density and body composition in a group of postmenopausal women. METHODS: One hundred and five Mahayana Buddhist nuns and 105 omnivorous women (average age = 62, range = 50-85) were randomly sampled from monasteries in Ho Chi Minh City and invited to participate in the study. By religious rule, the nuns do not eat meat or seafood (i.e., vegans). Bone mineral density (BMD) at the lumbar spine (LS), femoral neck (FN), and whole body (WB) was measured by DXA (Hologic QDR 4500). Lean mass, fat mass, and percent fat mass were also obtained from the DXA whole body scan. Dietary calcium and protein intakes were estimated from a validated food frequency questionnaire. RESULTS: There was no significant difference between vegans and omnivores in LSBMD (0.74 +/- 0.14 vs. 0.77 +/- 0.14 g/cm(2); mean +/- SD; P = 0.18), FNBMD (0.62 +/- 0.11 vs. 0.63 +/- 0.11 g/cm(2); P = 0.35), WBBMD (0.88 +/- 0.11 vs. 0.90 +/- 0.12 g/cm(2); P = 0.31), lean mass (32 +/- 5 vs. 33 +/- 4 kg; P = 0.47), and fat mass (19 +/- 5 vs. 19 +/- 5 kg; P = 0.77) either before or after adjusting for age. The prevalence of osteoporosis (T scores < or = -2.5) at the femoral neck in vegans and omnivores was 17.1% and 14.3% (P = 0.57), respectively. The median intake of dietary calcium was lower in vegans compared to omnivores (330 +/- 205 vs. 682 +/- 417 mg/day, P < 0.001); however, there was no significant correlation between dietary calcium and BMD. Further analysis suggested that whole body BMD, but not lumbar spine or femoral neck BMD, was positively correlated with the ratio of animal protein to vegetable protein. CONCLUSION: These results suggest that, although vegans have much lower intakes of dietary calcium and protein than omnivores, veganism does not have adverse effect on bone mineral density and does not alter body composition.",
"title": "Veganism, bone mineral density, and body composition: a study in Buddhist nuns."
},
{
"docid": "MED-3221",
"text": "Background The finding reported in a previous paper - alkalization of urine facilitates uric acid excretion - is contradictory to what one might expect to occur: because food materials for the alkalization of urine contain fewer purine bodies than those for acidification, less uric acid in alkaline urine should have been excreted than in acid urine. To make clear what component of uric acid excretion mechanisms is responsible for this unexpected finding, we simultaneously collected data for the concentration of both creatinine and uric acid in serum as well as in urine, in order to calculate both uric acid and creatinine clearances. Methods Within the framework of the Japanese government’s health promotion program, we made recipes which consisted of protein-rich and less vegetable-fruit food materials for H + -load (acidic diet) and others composed of less protein and more vegetable-fruit rich food materials (alkaline diet). This is a crossover study within some limitations. Healthy female students, who had no medical problems at the regular physical examination provided by the university, were enrolled in this consecutive 5-day study for each test. From whole-day collected urine, total volume, pH, organic acid, creatinine, uric acid, titratable acid and all cations (Na+,K+,Ca2+,Mg2+,NH4+) and anions (Cl−,SO42−,PO4−) necessary for the estimation of acid–base balance were measured. In the early morning before breakfast of the 1st, 3rd and 5th experimental day, we sampled 5 mL of blood to estimate the creatinine and uric acid concentration in serum. Results and discussion Urine pH reached a steady state 3 days after switching from ordinary daily diets to specified regimens. The amount of acid generated ([SO42−] + organic acid − gut alkali)was linearly related with the excretion of acid (titratable acid + [NH4+] − [HCO3−]), indicating that H + in urine is generated by the metabolic degradation of food materials. Uric acid and excreted urine pH retained a linear relationship, as reported previously. Among the five factors which are associated with calculating clearances for both uric acid and creatinine, we identified a conspicuous difference between acidic and alkaline diets in the uric acid concentration in serum as well as in urine; uric acid in the serum was higher in the acidic group than in the alkaline group, while uric acid in the urine in the acidic group was lower than that in the alkaline group. These changes of uric acid in acidic urine and in serum were reflected in the reduction of its clearance. From these observations, it is considered that uric acid may be reabsorbed more actively in acidic urine than in alkaline urine. Conclusion We conclude that alkalization of urine by eating nutritionally well-designed alkaline -prone food is effective for removing uric acid from the body.",
"title": "Effect of urine pH changed by dietary intervention on uric acid clearance mechanism of pH-dependent excretion of urinary uric acid"
},
{
"docid": "MED-3786",
"text": "This article describes the development of a series of choline- and betaine-controlled diets that were served to research subjects as part of an ongoing study of diet requirements in humans. These diets were developed based on the analysis of choline and betaine in individual foods. The calculated diets were compared with analyses of all foods combined into a single sample for each day. The laboratory analyses of choline and betaine in the whole-diet aliquots matched the estimated amounts in the diets that were calculated from the analyses of individual foods. These diets were adjusted for several levels of choline and betaine and were well accepted by research subjects who consumed them for a time period of up to 2 months. This article describes applications of this diet for use in clinical research on methyl-group requirements in humans and for use in clinical practice for counseling the client who requires a choline-controlled diet.",
"title": "Choline- and betaine-defined diets for use in clinical research and for the management of trimethylaminuria."
},
{
"docid": "MED-5184",
"text": "We examined the association of dietary lignan intake with estrogen receptor negative (ER-) and ER positive (ER+) breast cancer risk in a breast cancer case-control study. Among premenopausal women only, there was a reduced risk of ER- breast cancer for those in the highest compared to the lowest quartile of lignan intake suggesting that the observed negative association of lignans with breast cancer may be limited to ER- tumors.",
"title": "Dietary lignan intakes and risk of breast cancer by tumor estrogen receptor status."
},
{
"docid": "MED-3198",
"text": "BACKGROUND: Despite its high content of saturated fatty acids, cheese does not seem to increase plasma total and LDL-cholesterol concentrations when compared with an equivalent intake of fat from butter. This effect may be due to the high calcium content of cheese, which results in a higher excretion of fecal fat. OBJECTIVES: The objective was to compare the effects of diets of equal fat content rich in either hard cheese or butter or a habitual diet on blood pressure and fasting serum blood lipids, C-reactive protein, glucose, and insulin. We also examined whether fecal fat excretion differs with the consumption of cheese or butter. DESIGN: The study was a randomized dietary intervention consisting of two 6-wk crossover periods and a 14-d run-in period during which the subjects consumed their habitual diet. The study included 49 men and women who replaced part of their habitual dietary fat intake with 13% of energy from cheese or butter. RESULTS: After 6 wk, the cheese intervention resulted in lower serum total, LDL-, and HDL-cholesterol concentrations and higher glucose concentrations than did the butter intervention. Cheese intake did not increase serum total or LDL-cholesterol concentrations compared with the run-in period, during which total fat and saturated fat intakes were lower. Fecal fat excretion did not differ between the cheese and butter periods. CONCLUSION: Cheese lowers LDL cholesterol when compared with butter intake of equal fat content and does not increase LDL cholesterol compared with a habitual diet. This trial is registered at clinicaltrials.gov as NCT01140165.",
"title": "Cheese intake in large amounts lowers LDL-cholesterol concentrations compared with butter intake of equal fat content."
},
{
"docid": "MED-3369",
"text": "Background: Strategies are needed to increase children's intake of a variety of vegetables, including vegetables that are not well liked. Objective: We investigated whether incorporating puréed vegetables into entrées to reduce the energy density (ED; in kcal/g) affected vegetable and energy intake over 1 d in preschool children. Design: In this crossover study, 3- to 5-y-old children (n = 40) were served all meals and snacks 1 d/wk for 3 wk. Across conditions, entrées at breakfast, lunch, dinner, and evening snack were reduced in ED by increasing the proportion of puréed vegetables. The conditions were 100% ED (standard), 85% ED (tripled vegetable content), and 75% ED (quadrupled vegetable content). Entrées were served with unmanipulated side dishes and snacks, and children were instructed to eat as much as they liked. Results: The daily vegetable intake increased significantly by 52 g (50%) in the 85% ED condition and by 73 g (73%) in the 75% ED condition compared with that in the standard condition (both P < 0.0001). The consumption of more vegetables in entrées did not affect the consumption of the vegetable side dishes. Children ate similar weights of food across conditions; thus, the daily energy intake decreased by 142 kcal (12%) from the 100% to 75% ED conditions (P < 0.05). Children rated their liking of manipulated foods similarly across ED amounts. Conclusion: The incorporation of substantial amounts of puréed vegetables to reduce the ED of foods is an effective strategy to increase the daily vegetable intake and decrease the energy intake in young children. This trial was registered at clinicaltrials.gov as NCT01252433.",
"title": "Hiding vegetables to reduce energy density: an effective strategy to increase children's vegetable intake and reduce energy intake"
},
{
"docid": "MED-4919",
"text": "OBJECTIVE: Mass screening for celiac disease is controversial. The objective of this study was to determine whether detection of childhood celiac disease by mass screening improves long-term health status and health-related quality of life. METHODS: We conducted a prospective 10-year follow-up study of 32 children who were aged 2 to 4 years, had celiac disease identified by mass screening, and had a gluten-free diet (19) or a normal gluten-containing diet (13). The follow-up included assessments of general health status, celiac disease-associated symptoms, celiac disease-associated serum antibodies, and health-related quality of life. RESULTS: Ten years after mass screening, 81% of the children were adhering to a gluten-free diet. The health status improved in 66% of the treated children: in 41% by early treatment and in 25% by prevention of the gluten-dependent symptoms that they developed after diagnosis. For 19% of the children, treatment after screening would not have improved their health status, because they had no symptoms at screening and have remained symptom-free while consuming gluten. The health-related quality of life of the children with symptoms improved significantly after 1 year of gluten-free diet. Ten years after screening, the health-related quality of life of the children with celiac disease was similar to that of the reference population. CONCLUSION: Identification by mass screening led 10 years later to health improvement in 66% of children without deterioration of generic health-related quality of life. There is a good compliance after mass screening. In a research setting, delaying treatment for children without symptoms seems to be an option after a positive screening test. Long-term follow-up studies are needed to assess possible long-term complications in untreated, nonsymptomatic celiac disease.",
"title": "Long-term health and quality-of-life consequences of mass screening for childhood celiac disease: a 10-year follow-up study."
},
{
"docid": "MED-2588",
"text": "Objective Low-carbohydrate diets and their combination with high-protein diets have been gaining widespread popularity to control weight. In addition to weight loss, they may have favorable short-term effects on the risk factors of cardiovascular disease (CVD). Our objective was to elucidate their long-term effects on mortality and CVD incidence. Data sources MEDLINE, EMBASE, ISI Web of Science, Cochrane Library, and ClinicalTrials.gov for relevant articles published as of September 2012. Cohort studies of at least one year’s follow-up period were included. Review methods Identified articles were systematically reviewed and those with pertinent data were selected for meta-analysis. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) for all-cause mortality, CVD mortality and CVD incidence were calculated using the random-effects model with inverse-variance weighting. Results We included 17 studies for a systematic review, followed by a meta-analysis using pertinent data. Of the 272,216 people in 4 cohort studies using the low-carbohydrate score, 15,981 (5.9%) cases of death from all-cause were reported. The risk of all-cause mortality among those with high low-carbohydrate score was significantly elevated: the pooled RR (95% CI) was 1.31 (1.07–1.59). A total of 3,214 (1.3%) cases of CVD death among 249,272 subjects in 3 cohort studies and 5,081 (2.3%) incident CVD cases among 220,691 people in different 4 cohort studies were reported. The risks of CVD mortality and incidence were not statistically increased: the pooled RRs (95% CIs) were 1.10 (0.98–1.24) and 0.98 (0.78–1.24), respectively. Analyses using low-carbohydrate/high-protein score yielded similar results. Conclusion Low-carbohydrate diets were associated with a significantly higher risk of all-cause mortality and they were not significantly associated with a risk of CVD mortality and incidence. However, this analysis is based on limited observational studies and large-scale trials on the complex interactions between low-carbohydrate diets and long-term outcomes are needed.",
"title": "Low-Carbohydrate Diets and All-Cause Mortality: A Systematic Review and Meta-Analysis of Observational Studies"
},
{
"docid": "MED-4205",
"text": "Since the Second World War the consumer behaviour in developed countries changed drastically. Primarily there existed the demand for sufficient food after a period of starvation, afterwards the desire for higher quality was arising, whereas today most people ask for safe and healthy food with high quality. Therefore a united approach comprising consistent standards, sound science and robust controls is required to ensure consumers' health and to maintain consumers' confidence and satisfaction. Chemical analysis along the whole food chain downstream (tracking) from primary production to the consumer and upstream (tracing) from the consumer to primary production is an important prerequisite to ensure food safety and quality. In this frame the focus of the following paper is the \"chemical safety of meat and meat products\" taking into account inorganic as well as organic residues and contaminants, the use of nitrite in meat products, the incidence of veterinary drugs, as well as a Failure Mode and Effect Analysis (FMEA) system assessing (prioritizing) vulnerable food chain steps to decrease or eliminate vulnerability.",
"title": "Chemical safety of meat and meat products."
},
{
"docid": "MED-2353",
"text": "Summary Anti-Gal is the most abundant natural antibody in humans, constituting ∼ 1% of immunoglobulins. Anti-Gal is naturally produced also in apes and Old World monkeys. The ligand of anti-Gal is a carbohydrate antigen called the ‘α-gal epitope’ with the structure Galα1-3Galβ1-4GlcNAc-R. The α-gal epitope is present as a major carbohydrate antigen in non-primate mammals, prosimians and New World monkeys. Anti-Gal can contributes to several immunological pathogeneses. Anti-Gal IgE produced in some individuals causes allergies to meat and to the therapeutic monoclonal antibody cetuximab, all presenting α-gal epitopes. Aberrant expression of the α-gal epitope or of antigens mimicking it in humans may result in autoimmune processes, as in Graves' disease. α-Gal epitopes produced by Trypanosoma cruzi interact with anti-Gal and induce ‘autoimmune like’ inflammatory reactions in Chagas' disease. Anti-Gal IgM and IgG further mediate rejection of xenografts expressing α-gal epitopes. Because of its abundance, anti-Gal may be exploited for various clinical uses. It increases immunogenicity of microbial vaccines (e.g. influenza vaccine) presenting α-gal epitopes by targeting them for effective uptake by antigen-presenting cells. Tumour lesions are converted into vaccines against autologous tumour-associated antigens by intra-tumoral injection of α-gal glycolipids, which insert into tumour cell membranes. Anti-Gal binding to α-gal epitopes on tumour cells targets them for uptake by antigen-presenting cells. Accelerated wound healing is achieved by application of α-gal nanoparticles, which bind anti-Gal, activate complement, and recruit and activate macrophages that induce tissue regeneration. This therapy may be of further significance in regeneration of internally injured tissues such as ischaemic myocardium and injured nerves.",
"title": "Anti-Gal: an abundant human natural antibody of multiple pathogeneses and clinical benefits"
},
{
"docid": "MED-1801",
"text": "OBJECTIVE: In 1976, the Royal College of Physicians and the British Cardiac Society recommended eating less fatty red meat and more poultry instead because it was lean. However, the situation has changed since that time, with a striking increase in fat content of the standard broiler chicken. The aim of the present study was to report a snapshot of data on fat in chickens now sold to the public. DESIGN: Samples were obtained randomly between 2004 and 2008 from UK supermarkets, farm shops and a football club. The amount of chicken fat was estimated by emulsification and chloroform/methanol extraction. SETTING: Food sold in supermarkets and farms in England. SUBJECTS: Chicken samples. RESULTS: The fat energy exceeded that of protein. There has been a loss of n-3 fatty acids. The n-6:n-3 ratio was found to be as high as 9:1, as opposed to the recommendation of about 2:1. Moreover, the TAG level in the meat and whole bird mostly exceeded the proportion of phospholipids, which should be the higher for muscle function. The n-3 fatty acid docosapentaenoic acid (DPA, 22 : 5n-3) was in excess of DHA (22 : 6n-3). Previous analyses had, as usual for birds, more DHA than DPA. CONCLUSIONS: Traditional poultry and eggs were one of the few land-based sources of long-chain n-3 fatty acids, especially DHA, which is synthesized from its parent precursor in the green food chain. In view of the obesity epidemic, chickens that provide several times the fat energy compared with protein seem illogical. This type of chicken husbandry needs to be reviewed with regard to its implications for animal welfare and human nutrition.",
"title": "Modern organic and broiler chickens sold for human consumption provide more energy from fat than protein."
},
{
"docid": "MED-3928",
"text": "Seven patients with Parkinson's disease who experienced severe motor fluctuations in response to levodopa were studied in detail with relation to the effect of dietary protein on their motor function. The levodopa dose for each patient was not changed during the period of study, and no other antiparkinsonian drugs were used. Regular and high-protein diets resulted in a marked elevation in the plasma concentrations of large neutral amino acids (LNAAs) that are known to compete with levodopa for transport across the blood-brain barrier. Despite elevated plasma levodopa levels, all patients with elevated LNAA levels experienced parkinsonian symptoms. When the amino acid level dropped while plasma levodopa levels were elevated, patients experienced relief of these symptoms. On a low-protein diet, LNAA levels remained low and all patients were consistently dyskinetic throughout the day, even though the mean plasma levodopa levels were somewhat lower than when the patients consumed a high-protein diet. A redistribution diet that is virtually protein free until supper and then unrestricted until bedtime is tolerated by patients because this simple manipulation permits near-normal daytime motor function.",
"title": "Plasma levels of amino acids correlate with motor fluctuations in parkinsonism."
},
{
"docid": "MED-1715",
"text": "Summary Reduced function mutations in the insulin/IGF-I signaling pathway increase maximal lifespan and health span in many species. Calorie restriction (CR) decreases serum IGF-1 concentration by ~40%, protects against cancer and slows aging in rodents. However, the long-term effects of CR with adequate nutrition on circulating IGF-1 levels in humans are unknown. Here we report data from two long-term CR studies (1 and 6 years) showing that severe CR without malnutrition did not change IGF-1 and IGF-1 : IGFBP-3 ratio levels in humans. In contrast, total and free IGF-1 concentrations were significantly lower in moderately protein-restricted individuals. Reducing protein intake from an average of 1.67 g kg −1 of body weight per day to 0.95 g kg −1 of body weight per day for 3 weeks in six volunteers practicing CR resulted in a reduction in serum IGF-1 from 194 ng mL −1 to 152 ng mL −1 . These findings demonstrate that, unlike in rodents, long-term severe CR does not reduce serum IGF-1 concentration and IGF-1 : IGFBP-3 ratio in humans. In addition, our data provide evidence that protein intake is a key determinant of circulating IGF-1 levels in humans, and suggest that reduced protein intake may become an important component of anticancer and anti-aging dietary interventions.",
"title": "Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans"
},
{
"docid": "MED-1619",
"text": "BACKGROUND: Diets rich in carbohydrates with a low glycemic index and with high fiber content are associated with flat post-prandial rises of blood glucose, minimal post-prandial insulin secretion and maintenance of insulin sensitivity. Protective food commodities in the prevention of cardiovascular disease, insulin resistance syndrome or diabetes are crucial components of the vegetarian diet. AIM OF THE STUDY: Insulin resistance values were assessed in relation to different nutrition. Metabolic abnormality is a predictor of age-related diseases and can be more pronounced in obese subjects. Insulin resistance values in normal weight subjects of two different nutritional habits were correlated with age. METHODS: Fasting concentrations of glucose and insulin as well as calculated values of insulin resistance IR (HOMA) were assessed in two nutritional groups of apparently healthy adult subjects (age range 19 - 64 years) with normal weight (body mass index 18.6 - 25.0 kg/m(2)): a vegetarian group (95 long-term lacto-ovo-vegetarians; duration of vegetarianism 10.2 +/- 0.5 years) and a non-vegetarian control group (107 subjects of general population on traditional western diet). Intake of energy and main nutrients (fats, saccharides, proteins) was similar in both groups. RESULTS: Glucose and insulin concentrations and IR (HOMA) values were significantly lower in vegetarians (glucose 4.47 +/- 0.05 vs. 4.71 +/- 0.07 mmol/l; insulin 4.96 +/- 0.23 vs. 7.32 +/- 0.41 mU/l; IR (HOMA) 0.99 +/- 0.05 vs. 1.59 +/- 0.10). IR (HOMA) dependence on age was only significant in subjects on a western diet. A significant increase of IR was found already in the age range 31-40 years, compared to vegetarians and it continued in later age decades. Age independent and low insulin resistance values in vegetarians are a consequence of an effective diet prevention by long-term frequent consumption of protective food. Vegetarians had a significantly higher consumption of whole grain products, pulses, products from oat and barley. CONCLUSION: The results of age independent and low values of insulin resistance document a beneficial effect of long-term vegetarian nutrition in prevention of metabolic syndrome, diabetes and cardiovascular disease.",
"title": "No evidence of insulin resistance in normal weight vegetarians. A case control study."
},
{
"docid": "MED-2360",
"text": "Lyme-like illness (also known as southern tick-associated rash illness [STARI] or Masters disease) is vectored by the Lone Star tick (Amblyomma americanum). Lyme-like illness lesions, which are similar to the erythema migrans rash of Lyme disease, tend to have lymphocytic dermal infiltrates. With the exception of Borrelia lonestari, the possible causative agent or agents of Lyme-like illness have not been cultured. More research is needed to fully understand this newly recognized zoonosis. Clinicians are encouraged to increase their knowledge and awareness of this Lyme disease mimic.",
"title": "STARI, or Masters disease: Lone Star tick-vectored Lyme-like illness."
},
{
"docid": "MED-4051",
"text": "The food mutagens IQ (2-amino-3-methylimidazo[4,5-f]quinoline) and PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) are heterocyclic amines (HCA), generated when heating proteinaceous food. This study investigates the protective potential of the flavonoids quercetin (Q) and rutin (R) against oxidative stress induced in vitro by IQ and PhIP in lymphocytes from healthy individuals and untreated, newly diagnosed colon cancer patients using the Comet assay. In the presence of up to 500μM Q and R, the DNA damage resulting from a high dose of PhIP (75μM) or IQ (150μM) was significantly reduced (P<0.001) to levels comparable to six times lower IQ or 7.5 times lower PhIP doses. Lymphocytes from colon cancer patients had greater baseline DNA damage than those from healthy individuals (P<0.01) and this higher level of damage was also observed throughout in vitro treatment. Except for the >50years of age group and male gender, confounding factors such as smoking, drinking and/or dietary habits were not found to be significant. In conclusion, flavonoids reduced oxidative stress caused by food mutagens in vitro in lymphocytes of healthy individuals and colon cancer patients. Thus, dietary supplementation with flavonoid-rich vegetables and fruits may prove very effective in protecting against oxidative stress. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "The protective effect of the flavonoids on food-mutagen-induced DNA damage in peripheral blood lymphocytes from colon cancer patients."
},
{
"docid": "MED-2643",
"text": "The incidence and/or prevalence of health problems associated with endocrine-disruption have increased. Many chemicals have endocrine-disrupting properties, including bisphenol A, some organochlorines, polybrominated flame retardants, perfluorinated substances, alkylphenols, phthalates, pesticides, polycyclic aromatic hydrocarbons, alkylphenols, solvents, and some household products including some cleaning products, air fresheners, hair dyes, cosmetics, and sunscreens. Even some metals were shown to have endocrine-disrupting properties. Many observations suggesting that endocrine disruptors do contribute to cancer, diabetes, obesity, the metabolic syndrome, and infertility are listed in this paper. An overview is presented of mechanisms contributing to endocrine disruption. Endocrine disruptors can act through classical nuclear receptors, but also through estrogen-related receptors, membrane-bound estrogen-receptors, and interaction with targets in the cytosol resulting in activation of the Src/Ras/Erk pathway or modulation of nitric oxide. In addition, changes in metabolism of endogenous hormones, cross-talk between genomic and nongenomic pathways, cross talk with estrogen receptors after binding on other receptors, interference with feedback regulation and neuroendocrine cells, changes in DNA methylation or histone modifications, and genomic instability by interference with the spindle figure can play a role. Also it was found that effects of receptor activation can differ in function of the ligand.",
"title": "Endocrine-Disrupting Chemicals: Associated Disorders and Mechanisms of Action"
},
{
"docid": "MED-1655",
"text": "In 1940, a young German refugee physician scientist at Duke University in Durham, North Carolina began to treat patients with accelerated or \"malignant\" hypertension with a radical diet consisting of only white rice and fruit, with strikingly favorable results. He reported rapid reduction in blood pressure, rapid improvement in renal failure, papilledema, congestive heart failure and other manifestations of this previously fatal illness. This treatment was based on his theory that the kidney had both an excretory and a metabolic function, and that removing most of the sodium and protein burden from this organ enabled it to regain its normal ability to perform its more important metabolic functions. It was also effective in \"ordinary\" hypertension, in the absence of the dramatic vasculopathy of the accelerated form. The results were so dramatic that many experienced physicians suspected him of falsifying data. Among these results was the normalization of the ECG changes seen with hypertension. This paper reviews his published experience with this radical therapy, its controversial rise to fame, and its decline in popularity with the advent of effective antihypertensive drugs. It features the ECG changes seen in this then fatal disease, and the reversal of these changes by the rice diet. This treatment, though very difficult for the patient, produced effects which make it equal or superior to current multi-drug treatment of hypertension. A poorly known but important observation was that patients who were able to follow the regime, and who were slowly guided through a gradual modification of the diet over many months, were able to transition into a very tolerable low fat, largely vegetarian diet, while leading a normal, active life, without medications, indicating that the disease state had been permanently modified. Copyright © 2014 Elsevier Inc. All rights reserved.",
"title": "An archaeologic dig: a rice-fruit diet reverses ECG changes in hypertension."
},
{
"docid": "MED-3275",
"text": "In tissue cultures of normal adult and malignant mammalian cells, homocystine has been substituted for methionine in a medium rich in folic acid and cyanocobalamin. Normal adult cells thrive. Three highly malignant cell types from three different species, including man, die.",
"title": "The Effect of Replacement of Methionine by Homocystine on Survival of Malignant and Normal Adult Mammalian Cells in Culture"
},
{
"docid": "MED-2661",
"text": "This paper presents the results of an investigation on the occurrence of alkylphenols (APs) and their ethoxylates (APEs) in 8 edible marine species from the Adriatic Sea and tries to estimate the corresponding intake for the Italian population. Two crustaceans, Nephrops norvegicus (Norway lobster) and Squilla mantis (spottail mantis shrimp), plus six fish species, Engraulis enchrascicolus (anchovy), Scomber scombrus (Atlantic mackerel), Merluccius merluccius (European hake), Mullus barbatus (red mullet), Solea vulgaris (common sole) and Lophius piscatorius (angler) were analyzed for their content of nonylphenol (NP), octylphenol (OP) and octylphenol polyethoxylates (OPEs). These compounds were found in all analysed samples. NP was detected at the highest concentrations: 118-399 and 9.5-1431 ng g(-1) fresh weight (fw) respectively in crustaceans and fish. OP was found at respective levels of 2.7-4.7 and 0.3-3.8 ng g(-1) fw in crustaceans and fish, whereas OPE was determined at respective concentrations of 1.2-16.8 and 0.2-21.1 ng g(-1) fw in the same species. These results, together with those from a previous study on 4 edible mollusc, allow to estimate respective daily intakes for NP, OP, and OPE of about 12, 0.1, and 0.1 microg day(-1) for an Italian adult living along the Adriatic Coast. In relation to NP and OP, these intakes are much lower than the doses associated with toxic effects in laboratory animals (9 mg kg(-1) bw for rats). Nevertheless, data of exposure from other sources to these chemicals and others with similar biological characteristics are needed.",
"title": "Alkylphenols and alkylphenol ethoxylates contamination of crustaceans and fishes from the Adriatic Sea (Italy)."
},
{
"docid": "MED-4313",
"text": "BACKGROUND: Population-based studies have shown that vegetarians have lower body mass index than nonvegetarians, suggesting that vegetarian diet plans may be an approach for weight management. However, a perception exists that vegetarian diets are deficient in certain nutrients. OBJECTIVE: To compare dietary quality of vegetarians, nonvegetarians, and dieters, and to test the hypothesis that a vegetarian diet would not compromise nutrient intake when used to manage body weight. DESIGN: Cross-sectional analysis of National Health and Nutrition Examination Survey (1999-2004) dietary and anthropometric data. Diet quality was determined using United States Department of Agriculture's Healthy Eating Index 2005. Participants included adults aged 19 years and older, excluding pregnant and lactating women (N = 13,292). Lacto-ovo vegetarian diets were portrayed by intakes of participants who did not eat meat, poultry, or fish on the day of the survey (n = 851). Weight-loss diets were portrayed by intakes of participants who consumed 500 kcal less than their estimated energy requirements (n = 4,635). Mean nutrient intakes and body mass indexes were adjusted for energy, sex, and ethnicity. Using analysis of variance, all vegetarians were compared to all nonvegetarians, dieting vegetarians to dieting nonvegetarians, and nondieting vegetarians to nondieting nonvegetarians. RESULTS: Mean intakes of fiber, vitamins A, C, and E, thiamin, riboflavin, folate, calcium, magnesium, and iron were higher for all vegetarians than for all nonvegetarians. Although vegetarian intakes of vitamin E, vitamin A, and magnesium exceeded that of nonvegetarians (8.3 ± 0.3 vs 7.0 ± 0.1 mg; 718 ± 28 vs 603 ± 10 μg; 322 ± 5 vs 281 ± 2 mg), both groups had intakes that were less than desired. The Healthy Eating Index score did not differ for all vegetarians compared to all nonvegetarians (50.5 ± 0.88 vs 50.1 ± 0.33, P = 0.6). CONCLUSIONS: These findings suggest that vegetarian diets are nutrient dense, consistent with dietary guidelines, and could be recommended for weight management without compromising diet quality. Copyright © 2011 American Dietetic Association. Published by Elsevier Inc. All rights reserved.",
"title": "A vegetarian dietary pattern as a nutrient-dense approach to weight management: an analysis of the national health and nutrition examination survey..."
},
{
"docid": "MED-3136",
"text": "The objective of this study was to determine the influence of frequent and long-term consumption of legume seeds on colonic function. Two groups of subjects were studied--one group habitually consumed legume seeds as part of their normal diet, a second group only infrequently consumed legumes. No differences between these groups could be detected for fecal output and frequency, intestinal transit time, VFA excretion or fecal pH during 23-day study periods in which subjects consumed either their usual diet or 100 g red kidney beans, daily. However, the addition of beans to the diets of both groups provided significantly more dietary fiber, and produced greater fecal output and a higher concentration of VFA in feces. Fecal output appeared to be determined by two independent parameters--dietary fiber intake and VFA excretion. Beans provided a physiologically useful source of dietary fiber and favorably influenced colonic function.",
"title": "Influence of frequent and long-term bean consumption on colonic function and fermentation."
},
{
"docid": "MED-3217",
"text": "To investigate whether systemic acid-base equilibrium changes with aging in normal adult humans, we reviewed published articles reporting the acid-base composition of arterial, arterialized venous, or capillary blood in age-identified healthy subjects. We extracted or calculated blood hydrogen ion concentration ([H+]), plasma bicarbonate concentration ([HCO3(-)]), blood PCO2, and age, and computed a total of 61 age-group means, distributed among eight 10-year intervals from age 20 to 100 years. Using linear regression analysis, we found that with increasing age, there is a significant increase in the steady-state blood [H+] (p < .001), and reduction in steady-state plasma [HCO3(-)] (p < .001), indicative of a progressively worsening low-level metabolic acidosis. Blood PCO2 decreased with age (p < .05), in keeping with the expected respiratory adaptation to metabolic acidosis. Such age-related increasing metabolic acidosis may reflect in part the normal decline of renal function with increasing age. The role of age-related metabolic acidosis in the pathogenesis of the degenerative diseases of aging warrants consideration.",
"title": "Age and systemic acid-base equilibrium: analysis of published data."
},
{
"docid": "MED-4918",
"text": "Background & Aims The historical prevalence and long-term outcome of undiagnosed celiac disease (CD) are unknown. We investigated the long-term outcome of undiagnosed CD and whether the prevalence of undiagnosed CD has changed during the past 50 years. Methods This study included 9,133 healthy young adults at Warren Air Force Base (sera were collected between 1948 and 1954) and 12,768 sex-matched subjects from 2 recent cohorts from Olmsted County, Minnesota, with either similar years of birth (n=5,558) or age at sampling (n=7,210) to that of the Air Force cohort. Sera were tested for tissue transglutaminase and, if abnormal, for endomysial antibodies. Survival was measured during a follow-up period of 45 years in the Air Force cohort. The prevalence of undiagnosed CD between the Air Force cohort and recent cohorts was compared. Results Of 9,133 persons from the Air Force cohort, 14 (0.2%) had undiagnosed CD. In this cohort, during 45 years of follow-up, all-cause mortality was greater in persons with undiagnosed CD than among those who were seronegative (hazard ratio=3.9; 95% CI, 2.0–7.5; P<.001). Undiagnosed CD was found in 68 (0.9%) persons with similar age at sampling and 46 (0.8%) persons with similar years of birth. The rate of undiagnosed CD was 4.5-fold and 4-fold greater in the recent cohorts (respectively) than in the Air Force cohort (both P ≤ .0001). Conclusions During 45 years of follow-up, undiagnosed CD was associated with a nearly 4-fold increased risk of death. The prevalence of undiagnosed CD appears to have increased dramatically in the United States during the past 50 years.",
"title": "Increased Prevalence and Mortality in Undiagnosed Celiac Disease"
},
{
"docid": "MED-3215",
"text": "The average American diet, which is high in protein and low in fruits and vegetables, generates a large amount of acid, mainly as sulfates and phosphates. The kidneys respond to this dietary acid challenge with net acid excretion, as well as ammonium and titratable acid excretion. Concurrently, the skeleton supplies buffer by active resorption of bone. Indeed, calciuria is directly related to net acid excretion. Different food proteins differ greatly in their potential acid load, and therefore in their acidogenic effect. A diet high in acid-ash proteins causes excessive calcium loss because of its acidogenic content. The addition of exogenous buffers, as chemical salts or as fruits and vegetables, to a high protein diet results in a less acid urine, a reduction in net acid excretion, reduced ammonium and titratable acid excretion, and decreased calciuria. Bone resorption may be halted, and bone accretion may actually occur. Alkali buffers, whether chemical salts or dietary fruits and vegetables high in potassium, reverse acid-induced obligatory urinary calcium loss. We conclude that excessive dietary protein from foods with high potential renal acid load adversely affects bone, unless buffered by the consumption of alkali-rich foods or supplements.",
"title": "Excess dietary protein can adversely affect bone."
},
{
"docid": "MED-3229",
"text": "High-protein (HP) diets exert a hypercalciuric effect at constant levels of calcium intake, even though the effect may depend on the nature of the dietary protein. Lower urinary pH is also consistently observed for subjects consuming HP diets. The combination of these two effects was suspected to be associated with a dietary environment favorable for demineralization of the skeleton. However, increased calcium excretion due to HP diet does not seem to be linked to impaired calcium balance. In contrast, some data indicate that HP intakes induce an increase of intestinal calcium absorption. Moreover, no clinical data support the hypothesis of a detrimental effect of HP diet on bone health, except in a context of inadequate calcium supply. In addition, HP intake promotes bone growth and retards bone loss and low-protein diet is associated with higher risk of hip fractures. The increase of acid and calcium excretion due to HP diet is also accused of constituting a favorable environment for kidney stones and renal diseases. However, in healthy subjects, no damaging effect of HP diets on kidney has been found in either observational or interventional studies and it seems that HP diets might be deleterious only in patients with preexisting metabolic renal dysfunction. Thus, HP diet does not seem to lead to calcium bone loss, and the role of protein seems to be complex and probably dependent on other dietary factors and the presence of other nutrients in the diet.",
"title": "Protein intake, calcium balance and health consequences."
},
{
"docid": "MED-3313",
"text": "INTRODUCTION: Asbestos is banned in most Western countries but related malignancies are still of clinical concern because of their long latencies. This review identifies and addresses some controversial occupational and clinical aspects of asbestos-related malignancies. METHODS: Papers published in English from 1980 to 2009 were retrieved from PubMed. A total of 307 original articles were identified and 159 were included. ASSESSMENT OF EXPOSURE: The retrospective assessment of exposure is usually performed by using questionnaires and job exposure matrices and by careful collection of medical history. In this way crucial information about manufacturing processes and specific jobs can be obtained. In addition, fibers and asbestos bodies are counted in lung tissue, broncho-alveolar lavage, and sputum, but different techniques and interlaboratory variability hamper the interpretation of reported measurements. SCREENING FOR MALIGNANCIES: The effectiveness of low-dose chest CT screening in exposed workers is debatable. Several biomarkers have also been considered to screen individuals at risk for lung cancer and mesothelioma but reliable signatures are still missing. ATTRIBUTION OF LUNG CANCER: Exposures correlating with lung cancer are high and in the same range where asbestosis occurs. However, the unresolved question is whether the presence of fibrosis is a requirement for the attribution of lung cancer to asbestos. The etiology of lung cancer is difficult to define in cases of low-level asbestos exposure and concurrent smoking habits. MESOTHELIOMA: The diagnosis of malignant mesothelioma may also be difficult, because of procedures in sampling, fixation, and processing, and uses of immunohistochemical probes. CONCLUSIONS: Assessment of exposure is crucial and requires accurate medical and occupational histories. Quantitative analysis of asbestos body burden is better performed in digested lung tissues by counting asbestos bodies by light microscopy and/or uncoated fibers by transmission electron microscopy. The benefits of screenings for asbestos-related malignancies are equivocal. The attribution of lung cancer to asbestos exposure is difficult in a clinical setting because of the need to assess asbestos body burden and the fact that virtually all these patients are also tobacco smokers or former smokers. Given the premise that asbestosis is necessary to causally link lung cancer to asbestos, it follows that the assessment of both lung fibrosis and asbestos body burden is necessary.",
"title": "Occupational toxicology of asbestos-related malignancies."
},
{
"docid": "MED-2366",
"text": "Glycoconjugates and their antibodies are vital components of host-tumor interaction. This review concentrates on the oncological implications of research concerning the alpha gal triad; the alpha 1-->3 galactosyl epitope (alpha Gal), the enzyme responsible for its construction, alpha 1,3 galactosyl transferase (alpha 1-3GT), and its associated antibody: anti-gal. Alpha gal epitopes, previously assumed to be absent from human tissue, have been demonstrated on several human cancer cell lines, senescent red blood cells, and Graves' disease thyrocytes. Alpha-gal presence on neoplastic lines is correlated with increased metastatic formation in animal models. The mechanisms of human response to these neoantigens are complex, as natural anti-gal antibodies exist in high titers in normal sera, thus predicting immunological recognition of cells expressing alpha gal epitopes. Hypotheses vary regarding the pathogenic contributions of metastasis-associated phenomena such as de novo expression of alpha gal and its unmasking by desialylation. The means by which alpha gal is sporadically expressed in human tissue remain unknown, as the galactosyl transferase which produces this epitope in constitutively expressive animals has undergone significant mutation at the genomic level in humans. Pathological re-expression is presumed to require permissive changes at a cellular level. Detailing these alterations is a prerequisite to the comprehension of the metastatic phenotype. In this context, the possibility of therapeutic strategies affecting alpha gal expression are also discussed.",
"title": "A possible role for the alpha 1-->3 galactosyl epitope and the natural anti-gal antibody in oncogenesis."
},
{
"docid": "MED-3276",
"text": "Methionine is an essential amino acid with many key roles in mammalian metabolism such as protein synthesis, methylation of DNA and polyamine synthesis. Restriction of methionine may be an important strategy in cancer growth control particularly in cancers that exhibit dependence on methionine for survival and proliferation. Methionine dependence in cancer may be due to one or a combination of deletions, polymorphisms or alterations in expression of genes in the methionine de novo and salvage pathways. Cancer cells with these defects are unable to regenerate methionine via these pathways. Defects in the metabolism of folate may also contribute to the methionine dependence phenotype in cancer. Selective killing of methionine dependent cancer cells in co-culture with normal cells has been demonstrated using culture media deficient in methionine. Several animal studies utilizing a methionine restricted diet have reported inhibition of cancer growth and extension of a healthy life-span. In humans, vegan diets, which can be low in methionine, may prove to be a useful nutritional strategy in cancer growth control. The development of methioninase which depletes circulating levels of methionine may be another useful strategy in limiting cancer growth. The application of nutritional methionine restriction and methioninase in combination with chemotherapeutic regimens is the current focus of clinical studies. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "A review of methionine dependency and the role of methionine restriction in cancer growth control and life-span extension."
},
{
"docid": "MED-3292",
"text": "The human APOBEC3G protein is an innate anti-viral factor that can dominantly inhibit the replication of some endogenous and exogenous retroviruses. The prospects of purposefully harnessing such an anti-viral defense are under investigation. Here, long-term co-culture experiments were used to show that porcine endogenous retrovirus (PERV) transmission from pig to human cells is reduced to nearly undetectable levels by expressing human APOBEC3G in virus-producing pig kidney cells. Inhibition occurred by a deamination-independent mechanism, likely after particle production but before the virus could immortalize by integration into human genomic DNA. PERV inhibition did not require the DNA cytosine deaminase activity of APOBEC3G and, correspondingly, APOBEC3G-attributable hypermutations were not detected. In contrast, over-expression of the sole endogenous APOBEC3 protein of pigs failed to interfere significantly with PERV transmission. Together, these data constitute the first proof-of-principle demonstration that APOBEC3 proteins can be used to fortify the innate anti-viral defenses of cells to prevent the zoonotic transmission of an endogenous retrovirus. These studies suggest that human APOBEC3G-transgenic pigs will provide safer, PERV-less xenotransplantation resources and that analogous cross-species APOBEC3-dependent restriction strategies may be useful for thwarting other endogenous as well as exogenous retrovirus infections.",
"title": "The Restriction of Zoonotic PERV Transmission by Human APOBEC3G"
},
{
"docid": "MED-3310",
"text": "We observed five consecutive cases of Hypersensitivity Pneumonitis in subjects working in a salami factory. The workers had to clean the white mould growing on salami surface using a manual wire brush. The five patients (four female) had a mean age of 39 +/- 15 years; two were smokers. Three patients had an acute clinical presentation with fever, dyspnoea, dry cough, oxygen desaturation, and presented at the emergency department with suspected diagnosis of community acquired pneumonia. The mean latency for developing respiratory symptoms was 11.6 days. Pulmonary function test demonstrated a reduction in diffusing capacity (DLCO) in all 5 patients (60 +/- 15% of predicted value). Skin prick test was positive for Penicillium spp in 3 cases and for Cladosporium and Aspergillus spp in 2 others. Specific IgG antibodies against Penicillium spp were positive in 3 subjects; 2 were positive for Aspergillus Fumigatus. The prevailing radiological pattern was a ground glass appearance in the three patients with acute clinical onset and a centrilobular one in patients with subacute onset. All patients were advised to avoid exposure to the antigens. Follow-up visits including pulmonary function testing, and DLCO measurement were conducted at one, three and six months. HRCT was performed at six month. Four subjects had a complete radiological and clinical resolution after changing work. Only one patient was treated with oral steroids for severe dyspnoea and progressive reduction of DLCO, gaining a complete radiological and clinical stability at six months.",
"title": "A new type of Hypersensitivity Pneumonitis: salami brusher's disease."
},
{
"docid": "MED-1617",
"text": "Background Dietary modification via caloric restriction is associated with multiple effects related to improved metabolic and cardiovascular health. However, a mandated reduction in kilocalories is not well-tolerated by many individuals, limiting the long-term application of such a plan. The Daniel Fast is a widely utilized fast based on the Biblical book of Daniel. It involves a 21 day ad libitum food intake period, devoid of animal products and preservatives, and inclusive of fruits, vegetables, whole grains, legumes, nuts, and seeds. The purpose of the present study was to determine the efficacy of the Daniel Fast to improve markers of metabolic and cardiovascular disease risk. Methods 43 subjects (13 men; 30 women; 35 ± 1 yrs; range: 20-62 yrs) completed a 21 day period of modified food intake in accordance with detailed guidelines provided by investigators. All subjects purchased and prepared their own food. Following initial screening, subjects were given one week to prepare for the fast, after which time they reported to the lab for their pre-intervention assessment (day 1). After the 21 day fast, subjects reported to the lab for their post-intervention assessment (day 22). For both visits, subjects reported in a 12 hr fasted state, performing no strenuous physical activity during the preceding 24-48 hrs. At each visit, mental and physical health (SF-12 form), resting heart rate and blood pressure, and anthropometric variables were measured. Blood was collected for determination of complete blood count, metabolic panel, lipid panel, insulin, HOMA-IR, and C-reactive protein (CRP). Subjects' self-reported compliance, mood, and satiety in relation to the fast were also recorded. Diet records were maintained by all subjects during the 7 day period immediately prior to the fast (usual intake) and during the final 7 days of the fast. Results Subjects' compliance to the fast was 98.7 ± 0.2% (mean ± SEM). Using a 10 point scale, subjects' mood and satiety were both 7.9 ± 0.2. The following variables were significantly (p < 0.05) lower following the fast as compared to before the fast: white blood cell count (5.68 ± 0.24 vs. 4.99 ± 0.19 103·μL-1), blood urea nitrogen (13.07 ± 0.58 vs. 10.14 ± 0.59 mg·dL-1), blood urea nitrogen/creatinine (14.74 ± 0.59 vs. 11.67 ± 0.68), protein (6.95 ± 0.07 vs. 6.77 ± 0.06 g·dL-1), total cholesterol (171.07 ± 4.57 vs. 138.69 ± 4.39 mg·dL-1), LDL-C (98.38 ± 3.89 vs. 76.07 ± 3.53 mg·dL-1), HDL-C (55.65 ± 2.50 vs. 47.58 ± 2.19 mg·dL-1), SBP (114.65 ± 2.34 vs. 105.93 ± 2.12 mmHg), and DBP (72.23 ± 1.59 vs. 67.00 ± 1.43 mmHg). Insulin (4.42 ± 0.52 vs. 3.37 ± 0.35 μU·mL-1; p = 0.10), HOMA-IR (0.97 ± 0.13 vs.0.72 ± 0.08; p = 0.10), and CRP (3.15 ± 0.91 vs. 1.60 ± 0.42 mg·L-1; p = 0.13), were lowered to a clinically meaningful, albeit statistically insignificant extent. No significant difference was noted for any anthropometric variable (p > 0.05). As expected, multiple differences in dietary intake were noted (p < 0.05), including a reduction in total kilocalorie intake (2185 ± 94 vs. 1722 ± 85). Conclusion A 21 day period of modified dietary intake in accordance with the Daniel Fast is 1) well-tolerated by men and women and 2) improves several risk factors for metabolic and cardiovascular disease. Larger scale, randomized studies, inclusive of a longer time period and possibly a slight modification in food choice in an attempt to maintain HDL cholesterol, are needed to extend these findings.",
"title": "Effect of a 21 day Daniel Fast on metabolic and cardiovascular disease risk factors in men and women"
},
{
"docid": "MED-3932",
"text": "Background Caffeine consumption has been associated with a reduced risk of Parkinson disease. The association is strong and consistent in men, but uncertain in women, possibly because of an interaction with hormone replacement therapy. We sought to confirm these findings using data on Parkinson disease incidence in the CPS II Nutrition Cohort, a large prospective study of men and women. Methods We conducted a prospective study of caffeine intake and risk of PD within the Cancer Prevention Study II Nutrition Cohort. Intakes of coffee and other sources of caffeine were assessed at baseline. Incident cases of PD (n = 317; 197 men and 120 women) were confirmed by treating physicians and medical record review. Relative risks (RR) were estimated using proportional hazards models, adjusting for age, smoking and alcohol consumption. Results After adjustment for age, smoking and alcohol intake, high caffeine consumption was associated with a reduced risk of PD. The relative risk comparing the 5th to the 1st quintile of caffeine intake was 0.43 (CI: 0.26, 0.71, p-trend = <0.002) in men, and 0.61 (95% CI: 0.34, 1.09; p for trend =0.05) in women. Among women, this association was stronger among never users of hormone replacement therapy (RR=0.32) than among ever users (RR=0.81, p-interaction = 0.15). Consumption of decaffeinated coffee was not associated with PD risk. Conclusion Findings from this large prospective study of men and women are consistent with a protective effect of caffeine intake on PD incidence, with an attenuating influence of hormone replacement therapy in women.",
"title": "Caffeine and risk of Parkinson disease in a large cohort of men and women"
},
{
"docid": "MED-2359",
"text": "INTRODUCTION: ALPHA-GAL is a glycoconjugate present on cell membranes of mammals and bacteria but not humans who display anti-Gal antibodies (AB) in high titers provoked by the commensal gut flora. In the present study, we sought to determine the longitudinal course of alpha-Gal specific AB titers of all isotypes over 8 weeks among healthy adult subjects. Furthermore, we hypothesized that inflammatory bowel disease (IBD) patients display increased anti-Gal titers. MATERIALS AND METHODS: We drew serum from healthy probands (n=20) weekly for 8 weeks and obtained plasma samples of from patients suffering from Crohn's disease (n=20) and ulcerative colitis (n=20). We measured anti-Gal ABs of all isotypes and total immunoglobulin (Ig) content using an enzyme-linked immunosorbent assay technique. For statistical evaluation of the longitudinal titers, we calculated confidence intervals for the slopes of a random intercept model, comparing variances between and within the probands. For group comparisons, we performed paired student t-tests and Pearson correlations. RESULTS: Alpha-Gal specific IgG, IgM, IgD, and IgA titers remained unvaried within a narrow range upon longitudinal observation. Most probands did not display alpha-Gal specific IgE ABs. Crohn's disease patients showed highly increased alpha-Gal-specific IgA titers compared with control subjects (P<.01). CONCLUSION: Apart from IgE, alpha-Gal-specific ABs of all isotypes remained constant over longer time periods in healthy subjects. Thus, significant titer changes actually represent increased antigen exposure and a specific anti-alpha-Gal response. Crohn's disease patients display increased anti-Gal IgA titers compared with healthy controls, which reflects a chronically impaired mucosal gut barrier in this patient cohort. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "Anti-Gal titers in healthy adults and inflammatory bowel disease patients."
},
{
"docid": "MED-2587",
"text": "Recent research has demonstrated that successful simultaneous treatment of multiple risk factors including cholesterol, triglycerides, homocysteine, lipoprotein (a) [Lp(a)], fibrinogen, antioxidants, endothelial dysfunction, inflammation, infection, and dietary factors can lead to the regression of coronary artery disease and the recovery of viable myocardium. However, preliminary work revealed that a number of individuals enrolled in the original study went on popular high-protein diets in an effort to lose weight. Despite increasing numbers of individuals following high-protein diets, little or no information is currently available regarding the effect of these diets on coronary artery disease and coronary blood flow. Twenty-six people were studied for 1 year by using myocardial perfusion imaging (MPI), echocardiography (ECHO), and serial blood work to evaluate the extent of changes in regional coronary blood flow, regional wall motion abnormalities, and several independent variables known to be important in the development and progression of coronary artery disease. Treatment was based on homocysteine, Lp (a), C-reactive protein (C-RP), triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and fibrinogen levels. Each variable was independently treated as previously reported. MPI and ECHO were performed at the beginning and end of the study for each individual. The 16 people (treatment group/TG) studied modified their dietary intake as instructed. Ten additional individuals elected a different dietary regimen consisting of a \"high-protein\" (high protein group/HPG) diet, which they believed would \"improve\" their overall health. Patients in the TG demonstrated a reduction in each of the independent variables studied with regression in both the extent and severity of coronary artery disease (CAD) as quantitatively measured by MPI. Recovery of viable myocardium was seen in 43.75% of myocardial segments in these patients, documented with both MPI and ECHO evaluations. Individuals in the HPG showed worsening of their independent variables. Most notably, fibrinogen, Lp (a), and C-RP increased by an average of 14%, 106%, and 61% respectively. Progression of the extent and severity of CAD was documented in each of the vascular territories with an overall cumulative progression of 39.7%. The differences between progression and extension of disease in the HPG and the regression of disease in the TG were statistically (p<0.001) significant. Patients following recommended treatment for each of the independent variables were able to regress both the extent and severity of their coronary artery disease (CAD), as well as improve their myocardial wall motion (function) while following the prescribed medical and dietary guidelines. However, individuals receiving the same medical treatment but following a high-protein diet showed a worsening of independent risk factors, in addition to progression of CAD. These results would suggest that high-protein diets may precipitate progression of CAI) through increases in lipid deposition and inflammatory and coagulation pathways.",
"title": "The effect of high-protein diets on coronary blood flow."
},
{
"docid": "MED-1249",
"text": "The effect of dietary protein on the level of plasma cholesterol in young, healthy, normolipidemic women was investigated in two separate studies by feeding either a conventional diet containing mixed protein, or a plant protein diet in which the animal protein of the first diet was replaced by soy protein meat analogues and soy milk. The diets were similar with respect to carbohydrate, fat and sterol composition. The first study, lasting 73 days and involving six subjects, gave an indication that plasma cholesterol levels were lower on the plant protein diet. The second study, which incorporated a number of improvements based on experience, lasted 78 days and used a cross-over design involving two groups of five subjects each. In this study, the mean plasma cholesterol level was found to be significantly lower on the plant protein diet.",
"title": "Hypocholesterolemic effect of substituting soybean protein for animal protein in the diet of healthy young women."
},
{
"docid": "MED-4164",
"text": "PURPOSE OF REVIEW: This review discusses recent evidence that suggests a significant underestimation of protein requirements in adult humans. RECENT FINDINGS: Traditionally, total protein requirements for humans have been determined using nitrogen balance. The recent Dietary Reference Intake recommendations for mean and population-safe intakes of 0.66 and 0.8 g/kg/day, respectively, of high-quality protein in adult humans are based on a meta-analysis of nitrogen balance studies using single linear regression analysis. We reanalyzed existing nitrogen balance studies using two-phase linear regression analysis and obtained mean and safe protein requirements of 0.91 and 0.99 g/kg/day, respectively. The two-phase linear regression analysis is considered more appropriate for biological analysis of dose-response curves. Considering the inherent problems associated with the nitrogen balance method, we developed an alternative method, the indicator amino acid oxidation technique, to determine protein requirements The mean and population-safe requirements in adult men were determined to be 0.93 and 1.2 g/kg/day and are 41 and 50%, respectively, higher than the current Dietary Reference Intakes recommendations. SUMMARY: The indicator amino acid oxidation-based requirement values of 0.93 and 1.2 g protein/kg/day and the reanalysis of existing nitrogen balance studies are significantly higher than current recommendations. Therefore, there is an urgent need to reassess recommendations for protein intake in adult humans.",
"title": "Evidence that protein requirements have been significantly underestimated."
},
{
"docid": "MED-2355",
"text": "Anaphylaxis is a severe allergic reaction that can be rapidly progressing and fatal. In instances where the triggering allergen is not known, establishing the etiology of anaphylaxis is pivotal to long-term risk management. Our recent work has identified a novel IgE antibody (Ab) response to a mammalian oligosaccharide epitope, galactose-alpha-1,3-galactose (alpha-gal), that has been associated with two distinct forms of anaphylaxis: (1) immediate onset anaphylaxis during first exposure to intravenous cetuximab, and (2) delayed onset anaphylaxis 3–6 h after ingestion of mammalian food products (e.g., beef and pork). The results of our studies strongly suggest that tick bites are a cause, if not the only significant cause, of IgE Ab responses to alpha-gal in the southern, eastern and central United States. Patients with IgE Ab to alpha-gal continue to emerge and, increasingly, these cases involve children. This IgE Ab response cross-reacts with cat and dog but does not appear to pose a risk for asthma; however, it may impair diagnostic testing in some situations.",
"title": "Delayed Anaphylaxis to Red Meat in Patients with IgE Specific for Galactose alpha-1,3-Galactose (alpha-gal)"
},
{
"docid": "MED-3875",
"text": "BACKGROUND: Mammalian lignans, enterolactone (EL) and enterodiol (ED), have been shown to inhibit breast and colon carcinoma. To date, there have been no reports of the effect of lignans on prostatic carcinoma. We investigated the effects of ED and EL on three human prostate cancer cell lines (PC-3, DU-145 and LNCaP). MATERIALS AND METHODS: Cells were treated with either 0.1% (v/v) DMSO (vehicle) or 10-100 microM of EL, ED or genistein (positive control) for 72 hours. Cell viability was measured by the propidium iodide nuclei staining fluorometric assay with each assay performed in triplicate. RESULTS: At 10-100 microM, EL significantly inhibited the growth of all cell lines, whereas ED only inhibited PC-3 and LNCaP cells. While EL was a more potent growth inhibitor than ED, both were less potent than genistein. The dose for 50% growth inhibition of LNCaP cells (IC50) by EL was 57 microM, whereas IC50 was 100 microM for ED, (the observed IC50 for genistein was 25 microM). CONCLUSION: ED and EL suppress the growth of prostate cancer cells, and may do so via hormonally-dependent and independent mechanisms.",
"title": "Effect of mammalian lignans on the growth of prostate cancer cell lines."
},
{
"docid": "MED-3926",
"text": "Sixteen parkinsonian patients with daily fluctuations in the clinical response to levodopa have been placed on a redistribution protein diet. The diet was virtually protein-free until the evening meal and then unrestricted until bedtime. While on the redistribution protein diet, a group of patients (5 out of 16) had a clear and significant benefit from dietary therapy showing a definite reduction of diurnal motor performance fluctuations. In addition, all patients tended to show an improvement and a more constant response to levodopa treatment. A trial of redistribution protein diet appears a simple, reasonable, worthwhile approach to PD patients who begin to experience oscillating clinical response to levodopa treatment.",
"title": "Protein redistribution diet and antiparkinsonian response to levodopa."
},
{
"docid": "MED-2590",
"text": "Nineteen people without prior history of documented heart disease were studied for 8 months to determine the effect of treatment based on an immunologic unified theory of vascular disease. Subjects underwent myocardial perfusion imaging to quantify the extent and severity of coronary artery disease, along with assessment of wall motion abnormalities and ejection fraction by both nuclear and echocardiographic methods. These tests were repeated at the end of the study. Treatment consisted of dietary changes, treatment of cholesterol, triglycerides, homocysteine, lipoprotein (a), fibrinogen, C-reactive protein, and infection. Patients who followed the dietary recommendations demonstrated statistically reduced disease in all three major coronary arteries, whereas those individuals who followed high-protein diets demonstrated statistically greater levels of disease.",
"title": "Reversing heart disease in the new millennium--the Fleming unified theory."
},
{
"docid": "MED-3955",
"text": "BACKGROUND Polybrominated Diphenyl Ethers (PBDEs), widely used as flame retardants since the 1970s, have exhibited endocrine disruption in experimental studies. Tetra- to hexa-BDE congeners are estrogenic, while hepta-BDE and 6-OH-BDE-47 are antiestrogenic. Most PBDEs also have antiandrogenic activity. It is not clear, however, whether PBDEs affect human reproduction. OBJECTIVES The analysis was designed to investigate the potential endocrine disruption of PBDEs on the age at menarche in adolescent girls. METHODS We analyzed the data from a sample of 271 adolescent girls (age 12–19 years) in the National Health and Nutrition Examination Survey (NHANES), 2003–2004. We estimated the associations between individual and total serum BDEs (BDE-28, -47, -99, -100, -153, and -154, lipid adjusted) and mean age at menarche. We also calculated the risk ratios (RRs) and 95% confidence intervals (CI) for menarche prior to age 12 years in relation to PBDE exposure. RESULTS The median total serum BDE concentration was 44.7 ng/g lipid. Higher serum PBDE concentrations were associated with slightly earlier ages at menarche. Each natural log unit of total BDEs was related to a change of −0.10 (95% CI: −0.33, 0.13) years of age at menarche and a RR of 1.60 (95% CI: 1.12, 2.28) for experiencing menarche before 12 years of age, after adjustment for potential confounders. CONCLUSION These data suggest high concentrations of serum PBDEs during adolescence are associated with a younger age of menarche.",
"title": "Serum PBDEs and Age at Menarche in Adolescent Girls: Analysis of the National Health and Nutrition Examination Survey 2003–2004"
},
{
"docid": "MED-3270",
"text": "Aging affects all organisms and its basic mechanisms are expected to be conserved across species. Oxidation of proteins has been proposed to be one of the basic mechanisms linking oxygen radicals with the basic aging process. If oxidative damage to proteins is involved in aging, long-lived animals (which age slowly) should show lower levels of markers of this kind of damage than short-lived ones. However, this possibility has not been investigated yet. In this study, steady-state levels of markers of different kinds of protein damage--oxidation (glutamic and aminoadipic semialdehydes), mixed glyco- and lipoxidation (carboxymethyl- and carboxyethyllysine), lipoxidation (malondialdehydelysine) and amino acid composition--were measured in the heart of eight mammalian species ranging in maximum life span (MLSP) from 3.5 to 46 years. Oxidation markers were directly correlated with MLSP across species. Mixed glyco- and lipoxidation markers did not correlate with MLSP. However, the lipoxidation marker malondialdehydelysine was inversely correlated with MLSP (r2=0.85; P<0.001). The amino acid compositional analysis revealed that methionine is the only amino acid strongly correlated MLSP and that such correlation is negative (r2=0.93; P<0.001). This trait may contribute to lower steady-state levels of oxidized methionine residues in cellular proteins. These results reinforce the notion that high longevity in homeothermic vertebrates is achieved in part by constitutively decreasing the sensitivity of both tissue proteins and lipids to oxidative damage. This is obtained by modifying the constituent structural components of proteins and lipids, selecting those less sensitive to oxidative modifications.",
"title": "Protein methionine content and MDA-lysine adducts are inversely related to maximum life span in the heart of mammals."
},
{
"docid": "MED-2999",
"text": "Many of the commonest diseases in the economically more developed communities are characteristic of modern Western culture. Evidence is presented suggesting that they represent a failure of adaptation to the dramatic changes in diet that have been associated with the emergence of modern Western culture. Dietary changes aimed at the alleviation and prevention of these diseases are discussed and recommended.",
"title": "Western diseases and their emergence related to diet."
},
{
"docid": "MED-4037",
"text": "In the present study, 21 polycyclic aromatic hydrocarbon (PAH) congeners were measured in the exhaust stack of 3 types of restaurants: 9 Chinese, 7 Western, and 4 barbeque (BBQ). The total PAH concentration of BBQ restaurants (58.81 ± 23.89 μg m(-3)) was significantly higher than that of Chinese (20.99 ± 13.67 μg m(-3)) and Western (21.47 ± 11.44 μg m(-3)) restaurants. The total benzo[a]pyrene potency equivalent (B[a]P(eq)) concentrations, however, were highest in Chinese restaurants (1.82 ± 2.24 μg m(-3)), followed by Western (0.86 ± 1.43 μg m(-3), p<0.01) and BBQ-type restaurants (0.59 ± 0.55 μg m(-3), p<0.01). We further developed a probabilistic risk model to assess the incremental lifetime cancer risk (ILCR) for people exposed to carcinogenic PAHs. Because the exhaust stack directly affected the back-door neighbors of these restaurants, we were concerned with the real exposure of groups near the exhaust stack outlets of these restaurants. The ILCRs for total exposure of the neighbors (inhalation+dermal contact+ingestion) were 2.6-31.3, 1.5-14.8, and 1.3-12.2 × 10(-6) in Chinese, Western, and BBQ restaurants, respectively. We suggest that the maximum acceptable exposure time to the exhaust stack outlet area for Chinese, Western, and BBQ restaurants ranges between 5-19, 17-42, and 18-56 h month(-1), respectively, based on an ILCR of less than 10(-6). Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.",
"title": "Carcinogenic potencies of polycyclic aromatic hydrocarbons for back-door neighbors of restaurants with cooking emissions."
},
{
"docid": "MED-2369",
"text": "Background Carbohydrate moieties are frequently encountered in food and can elicit IgE responses, the clinical significance of which has been unclear. Recent work, however, has shown that IgE antibodies to galactose-α-1,3-galactose (α-gal), a carbohydrate commonly expressed on nonprimate mammalian proteins, are capable of eliciting serious, even fatal, reactions. Objective We sought to determine whether IgE antibodies to α-gal are present in sera from patients who report anaphylaxis or urticaria after eating beef, pork, or lamb. Methods Detailed histories were taken from patients presenting to the University of Virginia Allergy Clinic. Skin prick tests (SPTs), intradermal skin tests, and serum IgE antibody analysis were performed for common indoor, outdoor, and food allergens. Results Twenty-four patients with IgE antibodies to α-gal were identified. These patients described a similar history of anaphylaxis or urticaria 3 to 6 hours after the ingestion of meat and reported fewer or no episodes when following an avoidance diet. SPTs to mammalian meat produced wheals of usually less than 4 mm, whereas intradermal or fresh-food SPTs provided larger and more consistent wheal responses. CAP-RAST testing revealed specific IgE antibodies to beef, pork, lamb, cow’s milk, cat, and dog but not turkey, chicken, or fish. Absorption experiments indicated that this pattern of sensitivity was explained by an IgE antibody specific for α-gal. Conclusion We report a novel and severe food allergy related to IgE antibodies to the carbohydrate epitope α-gal. These patients experience delayed symptoms of anaphylaxis, angioedema, or urticaria associated with eating beef, pork, or lamb.",
"title": "Delayed anaphylaxis, angioedema, or urticaria after consumption of red meat in patients with IgE antibodies specific for galactose-α-1,3-galactose"
},
{
"docid": "MED-1620",
"text": "Background The Daniel Fast is a vegan diet that prohibits the consumption of animal products, refined foods, white flour, preservatives, additives, sweeteners, flavorings, caffeine, and alcohol. Following this dietary plan for 21 days has been demonstrated to improve blood pressure, LDL-C, and certain markers of oxidative stress, but it has also been shown to lower HDL-C. Krill oil supplementation has been shown to increase HDL-C. Methods We investigated the effects of following a Daniel Fast dietary plan with either krill oil supplementation (2 g/day) or placebo supplementation (coconut oil; 2 g/day) for 21 days. The subjects in this study (12 men and 27 women) were heterogeneous with respect to body mass index (BMI) (normal weight, overweight, and obese), blood lipids (normolipidemic and hyperlipidemic), blood glucose (normal fasting glucose, impaired fasting glucose, and type 2 diabetic), and blood pressure (normotensive and hypertensive). Results Krill oil supplementation had no effect on any outcome measure (all p > 0.05), and so the data from the krill oil group and the placebo group were collapsed and analyzed to examine the effects of following a 21-day Daniel Fast. Significant reductions were observed in LDL-C (100.6 ± 4.3 mg/dL vs. 80.0 ± 3.7 mg/dL), the LDL:HDL ratio (2.0 ± 0.1 vs. 1.7 ± 0.1), fasting blood glucose (101.4 ± 7.5 mg/dL vs. 91.7 ± 3.4 mg/dL), fasting blood insulin (7.92 ± 0.80 μU/mL vs. 5.76 ± 0.59 μU/mL), homeostasis model assessment of insulin resistance (HOMA-IR) (2.06 ± 0.30 vs. 1.40 ± 0.21), systolic BP (110.7 ± 2.2 mm Hg vs. 105.5 ± 1.7 mm Hg), and body weight (74.1 ± 2.4 kg vs. 71.5 ± 2.3 kg) (all p < 0.05). Conclusion Following a Daniel Fast dietary plan improves a variety of cardiometabolic parameters in a wide range of individuals in as little as 21 days, and these improvements are unaffected by krill oil supplementation. Trial registration Clinicaltrial.govNCT01378767",
"title": "A 21-day Daniel fast with or without krill oil supplementation improves anthropometric parameters and the cardiometabolic profile in men and women"
},
{
"docid": "MED-3142",
"text": "AIM: Soy foods are the major source of isoflavones, which are believed to play important roles in genesis of breast cancer and its progression. We here conducted a prospective study to evaluate the association of soy isoflavone food consumption with breast cancer prognosis. METHODS: A prospective study was performed from January 2004 and January 2006 in China. Trained interviewers conducted face-to-face interviews using a structured questionnaire to collect information on dietary habits and potential confounding factors. The relative risk [hazard ratio (HR)] and 95% CI were calculated from the Cox regression model for all significant predictors from cancer diagnosis to the endpoint of the study (event). RESULTS: After a median follow up of 52.1 months (range, 9-60 months), a total of 79 breast cancer related deaths were recorded in our study, risk being inversely associated with a high intake of soy isoflavone. With an average intake of soy isoflavone above 17.3 mg/day, the mortality of breast cancer can be reduced by about 38-36%. We also found the decreased breast cancer death with high soy protein intake, with a HR (95% CI) of 0.71 (0.52-0.98). Stratified analysis with reference to the ER status, further demonstrated a better prognosis of ER positive breast cancer with a high intake of soy isoflavone (HR 0.59, 0.40-0.93). CONCLUSION: Our study shows the soy food intake is associated with longer survival and low recurrence among breast cancer patients. A cohort study with a larger sample size and long term follow-up is now needed.",
"title": "Positive effects of soy isoflavone food on survival of breast cancer patients in China."
},
{
"docid": "MED-1188",
"text": "One hundred and eighteen missionaries working on 75 mission stations or hospitals in 24 sub-Saharan African countries provided information about their medical practice in the preceding year of 1981. Details were collected of the total number of patients seen and admitted during the year, and the number of cases of bloody diarrhoea, typhoid and inflammatory bowel disease. Over 1 million outpatients and about 190,000 inpatients were treated. These included 12,859 cases of bloody diarrhoea, of whom 1,914 had typhoid. Twenty-two cases of inflammatory bowel disease were also reported. Histological support was least available in West Africa and only 25% of hospitals had access to this facility. Nevertheless, the frequency with which inflammatory bowel disease in sub-Saharan Africa is difficult and limited by access to diagnostic facilities. It is likely to be some time before reliable estimates of the incidence and prevalence of Crohn's disease and ulcerative colitis in the rural African population can be made.",
"title": "Inflammatory bowel disease in rural sub-Saharan Africa: rarity of diagnosis in patients attending mission hospitals."
},
{
"docid": "MED-1712",
"text": "Diet contributes to over one-third of cancer deaths in the Western world, yet the factors in the diet that influence cancer are not elucidated. A reduction in caloric intake dramatically slows cancer progression in rodents, and this may be a major contribution to dietary effects on cancer. Insulin-like growth factor I (IGF-I) is lowered during dietary restriction (DR) in both humans and rats. Because IGF-I modulates cell proliferation, apoptosis, and tumorigenesis, the mechanisms behind the protective effects of DR may depend on the reduction of this multifaceted growth factor. To test this hypothesis, IGF-I was restored during DR to ascertain if lowering of IGF-I was central to slowing bladder cancer progression during DR. Heterozygous p53-deficient mice received a bladder carcinogen, p-cresidine, to induce preneoplasia. After confirmation of bladder urothelial preneoplasia, the mice were divided into three groups: (a) ad libitum; (b) 20% DR; and (c) 20% DR plus IGF-I (IGF-I/DR). Serum IGF-I was lowered 24% by DR but was completely restored in the IGF-I/DR-treated mice using recombinant IGF-I administered via osmotic minipumps. Although tumor progression was decreased by DR, restoration of IGF-I serum levels in DR-treated mice increased the stage of the cancers. Furthermore, IGF-I modulated tumor progression independent of changes in body weight. Rates of apoptosis in the preneoplastic lesions were 10 times higher in DR-treated mice compared to those in IGF/DR- and ad libitum-treated mice. Administration of IGF-I to DR-treated mice also stimulated cell proliferation 6-fold in hyperplastic foci. In conclusion, DR lowered IGF-I levels, thereby favoring apoptosis over cell proliferation and ultimately slowing tumor progression. This is the first mechanistic study demonstrating that IGF-I supplementation abrogates the protective effect of DR on neoplastic progression.",
"title": "Dietary restriction reduces insulin-like growth factor I levels, which modulates apoptosis, cell proliferation, and tumor progression in p53-defici..."
},
{
"docid": "MED-2482",
"text": "Previous studies have suggested that probiotic administration may have therapeutic and/or preventive effects on atopic dermatitis in infants; however, its role in allergic airway diseases remains controversial. To determine whether daily supplementation with specific Lactobacillus gasseri A5 for 8 weeks can improve the clinical symptoms and immunoregulatory changes in school children suffering from asthma and allergic rhinitis (AR). We conducted a randomized, double-blind, placebo-controlled study on school children (age, 6-12 years) with asthma and AR. The eligible study subjects received either L. gasseri A5 (n = 49) or a placebo (n = 56) daily for 2 months. Pulmonary function tests were performed, and the clinical severity of asthma and AR was evaluated by the attending physicians in the study period. Diary cards with records of the day- and nighttime peak expiratory flow rates (PEFR), symptoms of asthma, and AR scores of the patients were used for measuring the outcome of the treatment. Immunological parameters such as the total IgE and cytokine production by the peripheral blood mononuclear cells (PBMCs) were determined before and after the probiotic treatments. Our results showed the pulmonary function and PEFR increased significantly, and the clinical symptom scores for asthma and AR decreased in the probiotic-treated patients as compared to the controls. Further, there was a significant reduction in the TNF-α, IFN-γ, IL-12, and IL-13 production by the PBMCs following the probiotic treatment. In conclusion, probiotic supplementation may have clinical benefits for school children suffering from allergic airway diseases such as asthma and AR.",
"title": "Randomized placebo-controlled trial of lactobacillus on asthmatic children with allergic rhinitis."
},
{
"docid": "MED-2206",
"text": "Sweet potato is one of the crops selected for NASA's Advanced Life Support Program for potential long-duration lunar/Mars missions. This article presents recipes of products made from sweet potato and determines the consumer acceptability of products containing from 6% to 20% sweet potato on a dry weight basis. These products were developed for use in nutritious and palatable meals for future space explorers. Sensory evaluation (appearance/color, aroma, texture, flavor/taste, and overall acceptability) studies were conducted to determine the consumer acceptability of vegetarian products made with sweet potato using panelists at NASA/Johnson Space Center in Houston, TX. None of these products including the controls, contained any ingredient of animal origin with the exception of sweet potato pie. A 9-point hedonic scale (9 being like extremely and 1 being dislike extremely) was used to evaluate 10 products and compare them to similar commercially available products used as controls. The products tested were pancakes, waffles, tortillas, bread, pie, pound cake, pasta, vegetable patties, doughnuts, and pretzels. All of the products were either liked moderately or liked slightly with the exception of the sweet potato vegetable patties, which were neither liked nor disliked. Mean comparisons of sensory scores of sweet potato recipes and their controls were accomplished by using the Student t-test. Because of their nutritional adequacy and consumer acceptability, these products are being recommended to NASA's Advanced Life Support Program for inclusion in a vegetarian menu plan designed for lunar/Mars space missions.",
"title": "Consumer acceptance of vegetarian sweet potato products intended for space missions."
},
{
"docid": "MED-2449",
"text": "BACKGROUND: Recently, some common foods in daily life have been found to have anti-allergic effects. We have reported that tomato extract (TE) could possibly inhibit histamine release and mouse ear-swelling responses. Moreover, it is reported that TE could relieve the symptoms for Japanese cedar pollinosis. METHODS: To evaluate the anti-allergic effect of TE, we performed a randomized, double-blind, placebo-controlled study in 33 patients with perennial allergic rhinitis (PAR) using oral administration of TE (360 mg per day) or placebo for 8 weeks. RESULTS: We found that the sneezing score significantly decreased in the TE group at the end of the trial compared to the beginning (P < 0.05). There were decreasing tendencies of rhinorrhea and nasal obstruction in the TE group. The patients' quality of life was significantly improved in the TE group after 8 weeks of treatment (P < 0.05), but not in placebo group. A significant improvement in total symptom scores, combining sneezing, rhinorrhea and nasal obstruction, was observed after oral administration of TE for 8 weeks (P < 0.01). The safety of TE treatment was confirmed by laboratory tests and inspection of general conditions. CONCLUSIONS: TE can be expected to safely improve the nasal symptoms of PAR.",
"title": "An evaluation of the clinical efficacy of tomato extract for perennial allergic rhinitis."
},
{
"docid": "MED-4514",
"text": "Background Data on the long-term association between low-carbohydrate diets and mortality are sparse. Objective To examine the association of low-carbohydrate diets with mortality during 26 years of follow-up in women and 20 years in men. Design A prospective cohort study of women and men, followed from 1980 (women) or 1986 (men) until 2006. Low-carbohydrate diets, either animal-based (emphasizing animal sources of fat and protein), or vegetable-based (emphasizing vegetable sources of fat and protein) were computed from multiple validated food frequency questionnaire assessed during follow-up. Setting Nurses' Health Study and Health Professionals' Follow-up Study Participants 85,168 women (aged 34-59 years at baseline) and 44,548 men (aged 40-75 years at baseline) without heart disease, cancer, or diabetes. Measurement Investigator documented 12,555 deaths (2,458 cardiovascular, 5,780 cancer) in women and 8,678 deaths (2,746 cardiovascular, 2,960 cancer) in men. Results The overall low-carbohydrate score was associated with a modest increase in overall mortality in pooled analysis (Hazard Ratio, HR, comparing extreme deciles=1.12 (95% CI=1.01-1.24, p-trend=0.14). The animal low-carbohydrate score was associated with a higher all-cause mortality (pooled HR comparing extreme deciles=1.23, 95% CI=1.11-1.37, p-trend=0.05), cardiovascular mortality (corresponding HR=1.14, 95% CI=1.01-1.29, p-trend=0.029), and cancer mortality (corresponding HR=1.28, 95% CI 1.02-1.60, p for trend = 0.09). In contrast, a higher vegetable low-carbohydrate score was associated with lower all-cause (HR=0.80, 95% CI=0.75-0.85, p-trend<0.001) and cardiovascular mortality (HR=0.77, 95% CI=0.68-0.87, p-trend<0.001). Limitations Diet and lifestyle characteristics were assessed with some degree of error, however, sensitivity analyses indicated that results were not unlikely to be substantially affected by residual or confounding or an unmeasured confounder. In addition, participants were not a representative sample of the U.S. population. Conclusion A low-carbohydrate diet based on animal sources was associated with higher all-cause mortality in both men and women, whereas a vegetable-based low-carbohydrate diet was associated with lower all-cause and cardiovascular disease mortality rates. Primary funding source NIH grants CA87969, HL60712, and CA95589",
"title": "Low-carbohydrate diets and all-cause and cause-specific mortality: Two cohort Studies"
},
{
"docid": "MED-5204",
"text": "It is generally accepted that carbohydrate fermentation results in beneficial effects for the host because of the generation of short chain fatty acids, whereas protein fermentation is considered detrimental for the host's health. Protein fermentation mainly occurs in the distal colon, when carbohydrates get depleted and results in the production of potentially toxic metabolites such as ammonia, amines, phenols and sulfides. However, the effectivity of these metabolites has been established mainly in in vitro studies. In addition, some important bowel diseases such as colorectal cancer (CRC) and ulcerative colitis appear most often in the distal colon, which is the primary site of protein fermentation. Finally, epidemiological studies revealed that diets rich in meat are associated with the prevalence of CRC, as is the case in Western society. Importantly, meat intake not only increases fermentation of proteins but also induces increased intake of fat, heme and heterocyclic amines, which may also play a role in the development of CRC. Despite these indications, the relationship between gut health and protein fermentation has not been thoroughly investigated. In this review, the existing evidence about the potential toxicity of protein fermentation from in vitro animal and human studies will be summarized. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",
"title": "Relevance of protein fermentation to gut health."
},
{
"docid": "MED-2294",
"text": "The number of studies comparing nutritional quality of restrictive diets is limited. Data on vegan subjects are especially lacking. It was the aim of the present study to compare the quality and the contributing components of vegan, vegetarian, semi-vegetarian, pesco-vegetarian and omnivorous diets. Dietary intake was estimated using a cross-sectional online survey with a 52-items food frequency questionnaire (FFQ). Healthy Eating Index 2010 (HEI-2010) and the Mediterranean Diet Score (MDS) were calculated as indicators for diet quality. After analysis of the diet questionnaire and the FFQ, 1475 participants were classified as vegans (n = 104), vegetarians (n = 573), semi-vegetarians (n = 498), pesco-vegetarians (n = 145), and omnivores (n = 155). The most restricted diet, i.e., the vegan diet, had the lowest total energy intake, better fat intake profile, lowest protein and highest dietary fiber intake in contrast to the omnivorous diet. Calcium intake was lowest for the vegans and below national dietary recommendations. The vegan diet received the highest index values and the omnivorous the lowest for HEI-2010 and MDS. Typical aspects of a vegan diet (high fruit and vegetable intake, low sodium intake, and low intake of saturated fat) contributed substantially to the total score, independent of the indexing system used. The score for the more prudent diets (vegetarians, semi-vegetarians and pesco-vegetarians) differed as a function of the used indexing system but they were mostly better in terms of nutrient quality than the omnivores.",
"title": "Comparison of Nutritional Quality of the Vegan, Vegetarian, Semi-Vegetarian, Pesco-Vegetarian and Omnivorous Diet"
},
{
"docid": "MED-2335",
"text": "Xenohormesis is a biological principle that explains how environmentally stressed plants produce bioactive compounds that can confer stress resistance and survival benefits to animals that consume them. Animals can piggyback off products of plants' sophisticated stress response which has evolved as a result of their stationary lifestyle. Factors eliciting the plant stress response can judiciously be employed to maximize yield of health-promoting plant compounds. The xenohormetic plant compounds can, when ingested, improve longevity and fitness by activating the animal's cellular stress response and can be applied in drug discovery, drug production, and nutritional enhancement of diet.",
"title": "Xenohormesis: health benefits from an eon of plant stress response evolution"
},
{
"docid": "MED-2351",
"text": "Anti-Gal is a natural Ab abundantly produced in humans. It interacts specifically with the carbohydrate epitope Gal alpha 1-3Gal beta 1-4GlcNAc-R (termed the alpha-galactosyl epitope). This epitope is expressed in large amounts on thyrocytes of nonprimate mammals, but not of humans. We have previously found that binding of anti-Gal to alpha-galactosyl epitopes on porcine thyrocytes results in stimulatory effects similar to those exerted by thyroid-stimulating hormone (thyrotropin). In the present study, we tested the hypothesis that anti-Gal may contribute to Graves' disease (GD) pathogenesis by stimulation of the thyrocytes of patients with this autoimmune disorder. Anti-Gal binding and stimulatory effects were assessed in primary thyrocyte cultures. Anti-Gal specifically bound to GD thyrocytes and induced an increase in cAMP synthesis, 125I uptake, and DNA synthesis in these cells. Furthermore, the stimulatory effects of autologous sera on GD thyrocytes were greatly reduced after specific depletion of anti-Gal from these sera. No binding and no stimulatory effects of anti-Gal were observed, however, with normal human thyrocytes and with thyrocytes from thyrotoxic patients who lack thyroid-stimulating Igs or thyrotropin binding inhibiting Igs. These in vitro stimulatory effects of anti-Gal on GD thyrocytes suggest that this natural Ab may contribute to the in vivo continuous stimulation of thyrocytes in GD patients. The possibility that anti-Gal may stimulate GD thyrocytes via interaction with aberrantly expressed alpha-galactosyl epitopes on the thyroid-stimulating hormone receptor is discussed.",
"title": "Specific stimulation of Graves' disease thyrocytes by the natural anti-Gal antibody from normal and autologous serum."
},
{
"docid": "MED-3355",
"text": "OBJECTIVE: To evaluate the effects of a high-fat and low-fat diet on taste sensitivity to oleic acid (C18:1) in lean and overweight/obese (OW/OB) subjects. DESIGN: Randomized cross-over dietary intervention involving the consumption of a high-fat (>45% fat) and low-fat (<20% fat) diet, both consumed over a 4-week period. SUBJECTS: A total of 19 lean, mean age 33±13 years, mean body mass index (BMI) 23.2±2.2 kg m(-2) and 12 OW/OB, mean age 39.5±3 years, mean BMI 28±2.6 kg m(-2), subjects participated in the study, which measured taste thresholds for C18:1, fat perception and hedonic ratings for regular (RF) and lowered-fat (LF) foods before, and following consumption of a high- and low-fat diet. RESULTS: Consumption of the low-fat diet increased taste sensitivity to C18:1 among lean and OW/OB subjects (P<0.05) and increased the subjects ability to perceive small differences in the fat content of custard (P=0.05). Consumption of the high-fat diet significantly decreased taste sensitivity to C18:1 among lean subjects (P<0.05), with no change in sensitivity among OW/OB persons (P=0.609). The hedonic ratings for several RF and LF foods differed following the diets. CONCLUSION: Alterations in the fat content of the diet modulated taste sensitivity to C18:1 among lean subjects, which was increased following a 4-week period of fat restriction and attenuated following the high-fat diet. The failure of the high-fat diet to alter fatty acid taste thresholds among OW/OB subjects suggests that these individuals were 'adapted' to high-fat exposure, perhaps because of differences in habitual fat consumption. Taken together, these data suggest that excessive dietary fat attenuates nutrient sensing epithelia response in the oral cavity, which could be associated with changes in diet and weight status.",
"title": "Recent fat intake modulates fat taste sensitivity in lean and overweight subjects."
},
{
"docid": "MED-4206",
"text": "Vegetarian diets are rich in antioxidant phytochemicals. However, they may not act as antioxidants in vivo, and yet still have important signaling and regulatory functions. Some may act as pro-oxidants, modulating cellular redox tone and oxidizing redox sensitive sites. In this review, evidence for health benefits of vegetarian diets is presented from different perspectives: epidemiological, biomarker, evolutionary, and public health, as well as antioxidant. From the perspective of molecular connections between diet and health, evidence of a role for plasma ascorbic acid as a biomarker for future disease risk is presented. Basic concepts of redox-based cell signaling are presented, and effects of antioxidant phytochemicals on signaling, especially via redox tone, sulfur switches and the Antioxidant Response Element (ARE), are explored. Sufficient scientific evidence exists for public health policy to promote a plant-rich diet for health promotion. This does not need to wait for science to provide all the answers as to why and how. However, action and interplay of dietary antioxidants in the nonequilibrium systems that control redox balance, cell signaling, and cell function provide rich ground for research to advance understanding of orthomolecular nutrition and provide science-based evidence to advance public health in our aging population.",
"title": "Vegetarian diets and public health: biomarker and redox connections."
},
{
"docid": "MED-3772",
"text": "A clinical link exists between severe dehydration and cognitive performance. Using rapid and severe water loss induced either by intense exercise and/or heat stress, initial studies suggested there were alterations in short-term memory and cognitive function related to vision, but more recent studies have not all confirmed these data. Some studies argue that water loss is not responsible for the observations made, and studies compensating water losses have failed to prevent the symptoms. Studies in children have suggested that drinking extra water helps cognitive performance, but these data rely on a small number of children. In older adults (mean age around 60) the data are not strong enough to support a relationship between mild dehydration and cognitive function. Data on frail elderly and demented people are lacking. Methodological heterogeneity in these studies are such that the relationship between mild dehydration and cognitive performance cannot be supported.",
"title": "Hydration and cognitive performance."
},
{
"docid": "MED-5293",
"text": "Summary Background Quantification of the disease burden caused by different risks informs prevention by providing an account of health loss different to that provided by a disease-by-disease analysis. No complete revision of global disease burden caused by risk factors has been done since a comparative risk assessment in 2000, and no previous analysis has assessed changes in burden attributable to risk factors over time. Methods We estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010. We estimated exposure distributions for each year, region, sex, and age group, and relative risks per unit of exposure by systematically reviewing and synthesising published and unpublished data. We used these estimates, together with estimates of cause-specific deaths and DALYs from the Global Burden of Disease Study 2010, to calculate the burden attributable to each risk factor exposure compared with the theoretical-minimum-risk exposure. We incorporated uncertainty in disease burden, relative risks, and exposures into our estimates of attributable burden. Findings In 2010, the three leading risk factors for global disease burden were high blood pressure (7·0% [95% uncertainty interval 6·2–7·7] of global DALYs), tobacco smoking including second-hand smoke (6·3% [5·5–7·0]), and alcohol use (5·5% [5·0–5·9]). In 1990, the leading risks were childhood underweight (7·9% [6·8–9·4]), household air pollution from solid fuels (HAP; 7·0% [5·6–8·3]), and tobacco smoking including second-hand smoke (6·1% [5·4–6·8]). Dietary risk factors and physical inactivity collectively accounted for 10·0% (95% UI 9·2–10·8) of global DALYs in 2010, with the most prominent dietary risks being diets low in fruits and those high in sodium. Several risks that primarily affect childhood communicable diseases, including unimproved water and sanitation and childhood micronutrient deficiencies, fell in rank between 1990 and 2010, with unimproved water we and sanitation accounting for 0·9% (0·4–1·6) of global DALYs in 2010. However, in most of sub-Saharan Africa childhood underweight, HAP, and non-exclusive and discontinued breastfeeding were the leading risks in 2010, while HAP was the leading risk in south Asia. The leading risk factor in Eastern Europe, most of Latin America, and southern sub-Saharan Africa in 2010 was alcohol use; in most of Asia, North Africa and Middle East, and central Europe it was high blood pressure. Despite declines, tobacco smoking including second-hand smoke remained the leading risk in high-income north America and western Europe. High body-mass index has increased globally and it is the leading risk in Australasia and southern Latin America, and also ranks high in other high-income regions, North Africa and Middle East, and Oceania. Interpretation Worldwide, the contribution of different risk factors to disease burden has changed substantially, with a shift away from risks for communicable diseases in children towards those for non-communicable diseases in adults. These changes are related to the ageing population, decreased mortality among children younger than 5 years, changes in cause-of-death composition, and changes in risk factor exposures. New evidence has led to changes in the magnitude of key risks including unimproved water and sanitation, vitamin A and zinc deficiencies, and ambient particulate matter pollution. The extent to which the epidemiological shift has occurred and what the leading risks currently are varies greatly across regions. In much of sub-Saharan Africa, the leading risks are still those associated with poverty and those that affect children. Funding Bill & Melinda Gates Foundation.",
"title": "A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010"
},
{
"docid": "MED-2274",
"text": "Objective To study the relation between cherry intake and the risk of recurrent gout attacks among individuals with gout. Methods We conducted a case-crossover study to examine associations of a set of putative risk factors with recurrent gout attacks. Individuals with gout were prospectively recruited and followed online for one year. Participants were asked about the following information when experiencing a gout attack: the onset date of the gout attack, symptoms and signs, medications (including anti-gout medications), and potential risk factors (including daily intake of cherries and cherry extract) during the 2-day period prior to the gout attack. We assessed the same exposure information over 2-day control periods. We estimated the risk of recurrent gout attacks related to cherry intake using conditional logistic regression. Results Our study included 633 individuals with gout. Cherry intake over a 2-day period was associated with a 35% lower risk of gout attacks compared with no intake (multivariate odds ratio [OR] = 0.65, 95% CI: 0.50-0.85). Cherry extract intake showed a similar inverse association (multivariate OR=0.55, 95% CI: 0.30-0.98). The effect of cherry intake persisted across subgroups by sex, obesity status, purine intake, alcohol use, diuretic use, and use of anti-gout medications. When cherry intake was combined with allopurinol use, the risk of gout attacks was 75% lower than periods without either exposure (OR=0.25, 95% CI: 0.15-0.42). Conclusions These findings suggest that cherry intake is associated with a lower risk of gout attacks.",
"title": "Cherry Consumption and the Risk of Recurrent Gout Attacks"
},
{
"docid": "MED-3312",
"text": "BACKGROUND: Heavy alcohol consumption, viral hepatitis, and diabetes are risk factors for hepatocellular carcinoma (HCC). However, to the authors' knowledge, the information concerning their interaction effect in patients with risk of HCC is sparse. METHODS: A population-based, case-control study of HCC was conducted during 1984-2002. The study involved 295 HCC cases and 435 age-, gender-, and race-matched control subjects among Hispanic and non-Hispanic whites and blacks in Los Angeles County, California. Lifestyle risk factors were ascertained through in-person interviews. Infections with the hepatitis B and C (HCV) viruses were determined using their serologic markers. RESULTS: Fourteen HCC cases but no control subjects tested positive for the hepatitis B surface antigen. Seropositivity for antibodies to HCV was associated with an odds ratio (OR) of 125 (95% confidence interval [95% CI], 17-909) for HCC, whereas seropositivity for antibodies to the hepatitis B core antigen was related to an OR of 2.9 (95% CI, 1.7-5.0). Heavy alcohol consumption and cigarette smoking were found to be independently associated with a statistically significant two to threefold increase in risk of HCC after adjustment for hepatitis B and C serology. Subjects with a history of diabetes had an OR of 2.7 (95% CI, 1.6-4.3) for HCC compared with nondiabetic subjects. A synergistic interaction on HCC risk was observed between heavy alcohol consumption and diabetes (OR = 4.2; 95% CI, 2.6-5.8), heavy alcohol consumption and viral hepatitis (OR = 5.5; 95% CI, 3.9-7.0), or between diabetes and viral hepatitis (OR = 4.8; 95% CI, 2.7-6.9). CONCLUSIONS: Heavy alcohol consumption, diabetes, and viral hepatitis were found to exert independent and synergistic effects on risk of HCC in U.S. blacks and whites. Copyright 2004 American Cancer Society.",
"title": "Synergism of alcohol, diabetes, and viral hepatitis on the risk of hepatocellular carcinoma in blacks and whites in the U.S."
},
{
"docid": "MED-3123",
"text": "DietCompLyf is a multi-centre prospective study designed to investigate associations between phytoestrogens - naturally occurring plant compounds with oestrogenic properties - and other diet and lifestyle factors with breast cancer recurrence and survival. 3159 women with grades I-III breast cancer were recruited 9-15 months post-diagnosis from 56 UK hospitals. Detailed information on clinico-pathological, diet, lifestyle and quality of life is collected annually up to 5 years. Biological samples have also been collected as a resource for subsequent evaluation. The characteristics of the patients and associations between pre-diagnosis intake of phytoestrogens (isoflavones and lignans; assessed using the EPIC-Norfolk UK 130 question food frequency questionnaire) and breast cancer (i) risk factors and (ii) prognostic factors are described for 1797 women who had complete data for all covariates and phytoestrogens of interest. Isoflavone intakes were higher in the patients who were younger at diagnosis, in the non-smokers, those who had breast-fed and those who took supplements. Lignan intakes were higher in patients with a higher age at diagnosis, in ex-smokers, those who had breast-fed, who took supplements, had a lower BMI at diagnosis, lower age at menarche and were nulliparous. No significant associations between pre-diagnosis phytoestrogen intake and factors associated with improved breast cancer prognosis were observed. The potential for further exploration of the relationship between phytoestrogens and breast cancer recurrence and survival, and for the establishment of evidence to improve dietary and lifestyle advice offered to patients following breast cancer diagnosis using DietCompLyf data is discussed. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.",
"title": "The DietCompLyf study: a prospective cohort study of breast cancer survival and phytoestrogen consumption."
},
{
"docid": "MED-2827",
"text": "Alternative and complementary therapeutic approaches, such as the use of a wide array of herbal, nutritional, and physical manipulations, are becoming popular for relieving symptoms of osteoarthritis (OA). The present study evaluated the efficacy of soy protein (SP) supplementation in relieving the pain and discomfort associated with OA. One hundred and thirty-five free-living individuals (64 men and 71 women) with diagnosed OA or with self-reported chronic knee joint pain not attributed to injury or rheumatoid arthritis were recruited for this double-blind, placebo-controlled, parallel design study. Study participants were assigned randomly to consume 40 g of either supplemental SP or milk-based protein (MP) daily for 3 months. Pain, knee range of motion, and overall physical activity were evaluated prior to the start of treatment and monthly thereafter. Serum levels of glycoprotein 39 (YKL-40), a marker of cartilage degradation, and insulin-like growth factor-I (IGF-I), a growth factor associated with cartilage synthesis, were assessed at baseline and at the end of the study. Overall, SP improved OA-associated symptoms such as range of motion and several factors associated with pain and quality of life in comparison to MP. However, these beneficial effects were mainly due to the effect of SP in men rather than women. Biochemical markers of cartilage metabolism further support the efficacy of SP in men as indicated by a significant increase in serum level of IGF-I and a significant decrease in serum level of YKL-40 compared to MP. This study is the first to provide evidence of possible beneficial effects of SP in the management of OA. Examining and verifying the long-term effects of SP on improving symptoms of OA, particularly in men, is warranted.",
"title": "Soy protein may alleviate osteoarthritis symptoms."
},
{
"docid": "MED-2458",
"text": "BACKGROUND: Antioxidant-rich diets are associated with reduced asthma prevalence in epidemiologic studies. We previously showed that short-term manipulation of antioxidant defenses leads to changes in asthma outcomes. OBJECTIVE: The objective was to investigate the effects of a high-antioxidant diet compared with those of a low-antioxidant diet, with or without lycopene supplementation, in asthma. DESIGN: Asthmatic adults (n = 137) were randomly assigned to a high-antioxidant diet (5 servings of vegetables and 2 servings of fruit daily; n = 46) or a low-antioxidant diet (≤2 servings of vegetables and 1 serving of fruit daily; n = 91) for 14 d and then commenced a parallel, randomized, controlled supplementation trial. Subjects who consumed the high-antioxidant diet received placebo. Subjects who consumed the low-antioxidant diet received placebo or tomato extract (45 mg lycopene/d). The intervention continued until week 14 or until an exacerbation occurred. RESULTS: After 14 d, subjects consuming the low-antioxidant diet had a lower percentage predicted forced expiratory volume in 1 s and percentage predicted forced vital capacity than did those consuming the high-antioxidant diet. Subjects in the low-antioxidant diet group had increased plasma C-reactive protein at week 14. At the end of the trial, time to exacerbation was greater in the high-antioxidant than in the low-antioxidant diet group, and the low-antioxidant diet group was 2.26 (95% CI: 1.04, 4.91; P = 0.039) times as likely to exacerbate. Of the subjects in the low-antioxidant diet group, no difference in airway or systemic inflammation or clinical outcomes was observed between the groups that consumed the tomato extract and those who consumed placebo. CONCLUSIONS: Modifying the dietary intake of carotenoids alters clinical asthma outcomes. Improvements were evident only after increased fruit and vegetable intake, which suggests that whole-food interventions are most effective. This trial was registered at http://www.actr.org.au as ACTRN012606000286549.",
"title": "Manipulating antioxidant intake in asthma: a randomized controlled trial."
},
{
"docid": "MED-4551",
"text": "Interest has increased in the possibility that maternal dietary intake during pregnancy might influence the development of allergic disorders in children. The present prospective study examined the association of maternal intake of selected foods high in fatty acids and specific types of fatty acids during pregnancy with the risk of suspected atopic eczema among Japanese infants aged 3-4 months. Subjects were 771 mother-child pairs. Information on maternal dietary intake during pregnancy was assessed with a validated self-administered diet history questionnaire. The term 'suspected atopic eczema' was used to define an outcome based on results of our questionnaire completed by mothers 3-4 months postpartum. The risk of suspected atopic eczema was 8.4% (n = 65). Higher maternal intake of meat during pregnancy was significantly associated with an increased risk of suspected atopic eczema in the offspring: the multivariate odds ratio (OR) for the highest vs. lowest quartile was 2.59 [95% confidence interval (CI): 1.15-6.17, p for trend = 0.01]. The positive association was strengthened when the definition of the outcome was confined to a definite physician's diagnosis of atopic eczema (n = 35): the multivariate OR between extreme quartiles was 3.53 (95% CI: 1.19-12.23, p for trend = 0.02). No material exposure-response relationships were observed between maternal intake of eggs, dairy products, fish, total fat, saturated fatty acids, monounsaturated fatty acids, n-3 polyunsaturated fatty acids, alpha-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, n-6 polyunsaturated fatty acids, linoleic acid, arachidonic acid and cholesterol and the ratio of n-3 to n-6 polyunsaturated fatty acid consumption and the risk of suspected atopic eczema. Higher maternal meat intake may increase the risk of infantile atopic eczema, whereas we found no evidence that maternal intake of fish and n-3 polyunsaturated fatty acids are preventive against infantile atopic eczema. (c) 2009 John Wiley & Sons A/S",
"title": "Maternal meat and fat consumption during pregnancy and suspected atopic eczema in Japanese infants aged 3-4 months: the Osaka Maternal and Child He..."
}
] |
[
{
"docid": "MED-1807",
"text": "BACKGROUND: As protein is considered to increase thermogenesis and satiety more than other macronutrients, it may have beneficial effects on prevention of weight gain and weight maintenance. OBJECTIVE: The objective of this study is to assess the association between the amount and type of dietary protein, and subsequent changes in weight and waist circumference (WC). METHODS: 89,432 men and women from five countries participating in European Prospective Investigation into Cancer and Nutrition (EPIC) were followed for a mean of 6.5 years. Associations between the intake of protein or subgroups of protein (from animal and plant sources) and changes in weight (g per year) or WC (cm per year) were investigated using gender and centre-specific multiple regression analyses. Adjustments were made for other baseline dietary factors, baseline anthropometrics, demographic and lifestyle factors and follow-up time. We used random effect meta-analyses to obtain pooled estimates across centres. RESULTS: Higher intake of total protein, and protein from animal sources was associated with subsequent weight gain for both genders, strongest among women, and the association was mainly attributable to protein from red and processed meat and poultry rather than from fish and dairy sources. There was no overall association between intake of plant protein and subsequent changes in weight. No clear overall associations between intakes of total protein or any of the subgroups and changes in WC were present. The associations showed some heterogeneity between centres, but pooling of estimates was still considered justified. CONCLUSION: A high intake of protein was not found associated with lower weight or waist gain in this observational study. In contrast, protein from food items of animal origin, especially meat and poultry, seemed to be positively associated with long-term weight gain. There were no clear associations for waist changes.",
"title": "Intake of total, animal and plant protein and subsequent changes in weight or waist circumference in European men and women: the Diogenes project."
},
{
"docid": "MED-1446",
"text": "Literature on the association of protein intake with body weight is inconsistent. Little is known about the relation of long-term protein intake to obesity. This study aimed to determine the association between protein intake and obesity. A cohort of 1,730 employed white men ages 40–55 years from the Chicago Western Electric Study was followed from 1958 to 1966. Diet was assessed twice with Burke’s comprehensive diet history method, at two baseline examinations; height, weight, and other covariates were measured annually by trained interviewers. Generalized estimating equation (GEE) was used to examine the relation of baseline total, animal, and vegetable protein intake to likelihood of being overweight or obese at sequential annual examinations. Dietary animal protein was positively related to overweight and obesity over seven years of follow up. With adjustment for potential confounders (age, education, cigarette smoking, alcohol intake, energy, carbohydrate and saturated fat intake, and history of diabetes or other chronic disease), the odds ratios (95% confidence intervals) for obesity were 4.62 (2.68–7.98, p for trend<0.01) for participants in the highest compared to the lowest quartile of animal protein and 0.58 (0.36, 0.95, p for trend=0.053) for those in the highest quartile of vegetable protein intake. A statistically significant, positive association was seen between animal protein intake and obesity; those in higher quartiles of vegetable protein intake had lower odds of being obese. These results indicate that animal and vegetable protein may relate differently to occurrence of obesity in the long run.",
"title": "Longitudinal association between animal and vegetable protein intake and obesity among adult males in the United States: the Chicago Western Electric Study"
},
{
"docid": "MED-1869",
"text": "Observational and clinical studies suggest that high protein intake, particularly protein from plant sources, might reduce blood pressure (BP). To examine the association of dietary protein with BP, we analysed data from PREMIER, an 18-month clinical trial (n=810) that examined the effects of two multi-component lifestyle modifications on BP. We examined the association of protein intake with BP, and in particular the independent relationship of plant and animal protein with BP. Multivariable linear regression analyses were performed with both cross-sectional and longitudinal data. Dietary plant protein was inversely associated with both systolic and diastolic BP in cross-sectional analyses at the 6-month follow-up (P=0.0045 and 0.0096, respectively). Fruit and vegetable intake was also inversely associated with both systolic and diastolic BP cross-sectionally at 6 months (P=0.0003 and 0.0157, respectively). In longitudinal analyses, a high intake of plant protein at 6 months was marginally associated with a reduction of both systolic and diastolic BP from baseline to 6 months only (P=0.0797 and 0.0866, respectively), independent of change in body weight and waist circumference. Furthermore, increased intake of plant protein, and fruits and vegetables was significantly associated with a lower risk of hypertension at 6 but not at 18 months. Results of this study indicate that plant protein had a beneficial effect on BP and was associated with a lower risk of hypertension at 6 months. Our data, in conjunction with other research, suggest that an increased intake of plant protein may be useful as a means to prevent and treat hypertension.",
"title": "The relationship between dietary protein intake and blood pressure: results from the PREMIER study."
},
{
"docid": "MED-1281",
"text": "The calcium ion (Ca2+) is a ubiquitous second messenger that is crucial for the regulation of a wide variety of cellular processes. The diverse transient signals transduced by Ca2+ are mediated by intracellular Ca2+-binding proteins, also known as Ca2+ sensors. A key obstacle to studying many Ca2+-sensing proteins is the difficulty in identifying the numerous downstream target interactions that respond to Ca2+-induced conformational changes. Among a number of Ca2+ sensors in the eukaryotic cell, calmodulin (CaM) is the most widespread and the best studied. Employing the mRNA display technique, we have scanned the human proteome for CaM-binding proteins and have identified and characterized a large number of both known and previously uncharacterized proteins that interact with CaM in a Ca2+-dependent manner. The interactions of several identified proteins with Ca2+/CaM were confirmed by using pull-down assays and coimmunoprecipitation. Many of the CaM-binding proteins identified belong to protein families such as the DEAD/H box proteins, ribosomal proteins, proteasome 26S subunits, and deubiquitinating enzymes, suggesting the possible involvement of Ca2+/CaM in different signaling pathways. The selection method described herein could be used to identify the binding partners of other calcium sensors on the proteome-wide scale.",
"title": "Scanning the human proteome for calmodulin-binding proteins"
},
{
"docid": "MED-5199",
"text": "Studies attempting to evaluate protein assimilation in humans have hitherto relied on either ileostomy subjects or intubation techniques. The availability of stable isotope-labeled protein allowed us to determine the amount and fate of dietary protein escaping digestion and absorption in the small intestine of healthy volunteers using noninvasive tracer techniques. Ten healthy volunteers were studied once after ingestion of a cooked test meal, consisting of 25 g of (13)C-, (15)N-, and (2)H-labeled egg protein, and once after ingestion of the same but raw meal. Amounts of 5.73% and 35.10% (P < 0.005) of cooked and raw test meal, respectively, escaped digestion and absorption in the small intestine. A significantly higher percentage of the malabsorbed raw egg protein was recovered in urine as fermentation metabolites. These results 1) confirm that substantial amounts of even easily digestible proteins may escape assimilation in healthy volunteers and 2) further support the hypothesis that the metabolic fate of protein in the colon is affected by the amount of protein made available.",
"title": "Amount and fate of egg protein escaping assimilation in the small intestine of humans."
},
{
"docid": "MED-1425",
"text": "We examined the correlation between the incidence of Crohn disease and dietary change in a relatively homogeneous Japanese population. The incidence and daily intake of each dietary component were compared annually from 1966 to 1985. The univariate analysis showed that the increased incidence of Crohn disease was strongly (P < 0.001) correlated with increased dietary intake of total fat (r = 0.919). animal fat (r = 0.880), n-6 polyunsaturated fatty acids (r = 0.883), animal protein (r = 0.908), milk protein (r = 0.924), and the ratio of n-6 to n-3 fatty acid intake (r = 0.792). It was less correlated with intake of total protein (r = 0.482, P < 0.05), was not correlated with intake of fish protein (r = 0.055, P > 0.1), and was inversely correlated with intake of vegetable protein (r = -0.941, P < 0.001). The multivariate analysis showed that increased intake of animal protein was the strongest independent factor with a weaker second factor, an increased ration of n-6 to n-3 polyunsaturated fatty acids. The present study in association with reported clinical studies suggests that increased dietary intake of animal protein and n-6 polyunsaturated fatty acids with less n-3 polyunsaturated fatty acids may contribute to the development of Crohn disease.",
"title": "Epidemiologic analysis of Crohn disease in Japan: increased dietary intake of n-6 polyunsaturated fatty acids and animal protein relates to the inc..."
},
{
"docid": "MED-2943",
"text": "BACKGROUND: Western diets, which typically contain large amounts of energy-dense processed foods, together with a sedentary lifestyle are associated with increased cardiometabolic risk. We evaluated the long-term effects of consuming a low-calorie low-protein vegan diet or performing regular endurance exercise on cardiometabolic risk factors. METHODS: In this cross-sectional study, cardiometabolic risk factors were evaluated in 21 sedentary subjects, who had been on a low-calorie low-protein raw vegan diet for 4.4 +/- 2.8 years, (mean age, 53.1 +/- 11 yrs), 21 body mass index (BMI)-matched endurance runners consuming Western diets, and 21 age- and gender-matched sedentary subjects, consuming Western diets. RESULTS: BMI was lower in the low-calorie low-protein vegan diet (21.3 +/- 3.1 kg/m(2)) and endurance runner (21.1 +/- 1.6 kg/m(2)) groups than in the sedentary Western diet group (26.5 +/- 2.7 kg/m(2)) (p < 0.005). Plasma concentrations of lipids, lipoproteins, glucose, insulin, C-reactive protein, blood pressure (BP), and carotid artery intima-media thickness were lower in the low-calorie low-protein vegan diet and runner groups than in the Western diet group (all p < 0.05). Both systolic and diastolic BP were lower in the low-calorie low-protein vegan diet group (104 +/- 15 and 62 +/- 11 mm Hg) than in BMI-matched endurance runners (122 +/- 13 and 72 +/- 9 mmHg) and Western diet group (132 +/- 14 and 79 +/- 8 mm Hg) (p < 0.001); BP values were directly associated with sodium intake and inversely associated with potassium and fiber intake. CONCLUSIONS: Long-term consumption of a low-calorie low-protein vegan diet or regular endurance exercise training is associated with low cardiometabolic risk. Moreover, our data suggest that specific components of a low-calorie low-protein vegan diet provide additional beneficial effects on blood pressure.",
"title": "Long-term low-calorie low-protein vegan diet and endurance exercise are associated with low cardiometabolic risk."
},
{
"docid": "MED-4509",
"text": "Hypercholesterolemia is a major modifiable risk factor for cardiovascular disease. Some, but not all, studies have shown that soy protein intake decreases total and low-density lipoprotein cholesterol and triglycerides and increases high-density lipoprotein cholesterol. The objective of this meta-analysis was to examine the effect of soy protein supplementation on serum lipid levels in adults. English language articles were retrieved by searching MEDLINE (1966 to February 2005) and the bibliographies of the retrieved articles. A total of 41 randomized controlled trials in which isolated soy protein supplementation was the only intervention and the net changes in serum lipids during intervention were reported. Information on study design, sample size, participant characteristics, intervention, follow-up duration, and treatment outcomes was independently abstracted using a standardized protocol. Using a random-effects model, data from each study were pooled and weighted by the inverse of their variance. Soy protein supplementation was associated with a significant reduction in mean serum total cholesterol (-5.26 mg/dl, 95% confidence interval [CI] -7.14 to -3.38), low-density lipoprotein cholesterol (-4.25 mg/dl, 95% CI -6.00 to -2.50), and triglycerides (-6.26 mg/dl, 95% CI -9.14 to -3.38) and a significant increase in high-density lipoprotein cholesterol (0.77 mg/dl, 95% CI 0.20 to 1.34). Meta-regression analyses showed a dose-response relation between soy protein and isoflavone supplementation and net changes in serum lipids. These results indicate that soy protein supplementation reduces serum lipids among adults with or without hypercholesterolemia. In conclusion, replacing foods high in saturated fat, trans-saturated fat, and cholesterol with soy protein may have a beneficial effect on coronary risk factors.",
"title": "A meta-analysis of the effect of soy protein supplementation on serum lipids."
},
{
"docid": "MED-1323",
"text": "Background: Fat and protein sources may influence whether low-carbohydrate diets are associated with type 2 diabetes (T2D). Objective: The objective was to compare the associations of 3 low-carbohydrate diet scores with incident T2D. Design: A prospective cohort study was conducted in participants from the Health Professionals Follow-Up Study who were free of T2D, cardiovascular disease, or cancer at baseline (n = 40,475) for up to 20 y. Cumulative averages of 3 low-carbohydrate diet scores (high total protein and fat, high animal protein and fat, and high vegetable protein and fat) were calculated every 4 y from food-frequency questionnaires and were associated with incident T2D by using Cox models. Results: We documented 2689 cases of T2D during follow-up. After adjustments for age, smoking, physical activity, coffee intake, alcohol intake, family history of T2D, total energy intake, and body mass index, the score for high animal protein and fat was associated with an increased risk of T2D [top compared with bottom quintile; hazard ratio (HR): 1.37; 95% CI: 1.20, 1.58; P for trend < 0.01]. Adjustment for red and processed meat attenuated this association (HR: 1.11; 95% CI: 0.95, 1.30; P for trend = 0.20). A high score for vegetable protein and fat was not significantly associated with the risk of T2D overall but was inversely associated with T2D in men aged <65 y (HR: 0.78; 95% CI: 0.66, 0.92; P for trend = 0.01, P for interaction = 0.01). Conclusions: A score representing a low-carbohydrate diet high in animal protein and fat was positively associated with the risk of T2D in men. Low-carbohydrate diets should obtain protein and fat from foods other than red and processed meat.",
"title": "Low-carbohydrate diet scores and risk of type 2 diabetes in men"
},
{
"docid": "MED-4745",
"text": "Early puberty onset is associated with hormone-related cancers, but whether diet in childhood influences pubertal timing is controversial. We examined the association of protein intake in early and mid-childhood with the ages at take-off of the pubertal growth spurt (ATO), peak height velocity (APHV), and menarche in girls and voice break in boys using data from the longitudinal Dortmund Nutritional and Anthropometric Longitudinally Designed Study. Among participants who provided 3-d weighed dietary records at 12 mo, 18-24 mo, 3-4 y, and 5-6 y, 112 had sufficient anthropometric measurements between 6 and 13 y to allow estimation of ATO. Life-course plots were used to identify critical periods of total, animal, and vegetable protein intake (percentage of total energy intake) for pubertal timing. At these ages, the association between tertiles of protein intake (T1-T3) and the outcomes was investigated using multiple linear regression analysis. A higher total and animal protein intake at 5-6 y was related to an earlier ATO. In the highest tertile of animal protein intake at 5-6 y, ATO occurred 0.6 y earlier than in the lowest [(mean, 95% CI) T1: 9.6, 9.4-9.9 vs. T2: 9.4, 9.1-9.7 vs. T3: 9.0, 8.7-9.3 y; P-trend = 0.003, adjusted for sex, total energy, breast-feeding, birth year, and paternal university degree]. Similar findings were seen for APHV (P-trend = 0.001) and the timing of menarche/voice break (P-trend = 0.02). Conversely, a higher vegetable protein intake at 3-4 and 5-6 y was related to later ATO, APHV, and menarche/voice break (P-trend = 0.02-0.04). These results suggest that animal and vegetable protein intake in mid-childhood might be differentially related to pubertal timing.",
"title": "Dietary protein intake throughout childhood is associated with the timing of puberty."
},
{
"docid": "MED-1135",
"text": "The hypothesis that the incidence of calcium stone disease is related to the consumption of animal protein has been examined. Within the male population, recurrent idiopathic stone formers consumed more animal protein than did normal subjects. Single stone formers had animal protein intakes intermediate between those of normal men and those of recurrent stone formers. A high animal protein intake caused a significant increase in the urinary excretion of calcium, oxalate and uric acid, 3 of the 6 main urinary risk factors for calcium stone formation. The overall relative probability of forming stones, calculated from the combination of the 6 main urinary risk factors, was markedly increased by a high animal protein diet. Conversely, a low animal protein intake, such as taken by vegetarians, was associated with a low excretion of calcium, oxalate and uric acid and a low relative probability of forming stones.",
"title": "Should recurrent calcium oxalate stone formers become vegetarians?"
},
{
"docid": "MED-1426",
"text": "BACKGROUND: To evaluate the influence of increased dietary protein intake on bacterial colonic metabolism in healthy volunteers. METHODS: Short chain fatty acids, ammonia, and volatile organic compounds in faecal samples, and phenols in the urine of five volunteers were measured after one week of basal nutrient intake and and after one week of a diet supplemented with a protein rich food (Fortimel; Nutricia, Zoetermeer, The Netherlands). Paired t tests and factor analysis were used for statistical analysis. RESULTS: Total energy and resistant carbohydrate intake remained unchanged in each study period. The percentage energy intake delivered as dietary protein, increased significantly (from 15.4% to 23.8%; p = 0.007) during supplement intake. A significant increase in faecal ammonia (p = 0.002), faecal valeric acid (p = 0.02), and urinary p-cresol (p = 0.04) was noted during supplementary protein intake. A total of 120 different volatile compounds were isolated from the faecal samples of which 10 increased significantly during dietary protein supplementation. The change in volatile pattern, especially for S containing metabolites, was clearly shown by a factor analysis model which made a distinction between the two dietary regimens for all volunteers. CONCLUSION: An increase in dietary protein leads to altered products formation by colonic metabolism, mainly reflected by an increase in faecal ammonia, faecal volatile S substances, and urinary p-cresol.",
"title": "Influence of dietary protein supplements on the formation of bacterial metabolites in the colon."
},
{
"docid": "MED-5334",
"text": "Until recently, intact protein that is rich in tryptophan was not seen as an alternative to pharmaceutical-grade tryptophan because protein also contains large neutral amino acids (LNAAs) that compete for transport sites across the blood-brain barrier. Recent evidence indicates that when deoiled gourd seed (a rich source of tryptophan with approximately 22 mg/g protein) is combined with glucose (a carbohydrate that reduces serum levels of competing LNAAs) a clinical effect similar to that of pharmaceutical-grade tryptophan is achieved. Objective and subjective measures of anxiety in those suffering from social phobia (also known as social anxiety disorder) were employed to measure changes in anxiety in response to a stimulus as part of a double-blind, placebo-controlled, crossover study with a wash-out period of 1 week between study sessions. Subjects were randomly assigned to start with either (i) protein-source tryptophan (deoiled gourd seed) in combination with carbohydrate or (ii) carbohydrate alone. One week after the initial session, subjects returned for a follow-up session and received the opposite treatment of that received at the first session. All 7 subjects who began the study completed the 2-week protocol. Protein-source tryptophan with carbohydrate, but not carbohydrate alone, resulted in significant improvement on an objective measure of anxiety. Protein-source tryptophan combined with a high glycemic carbohydrate is a potential anxiolytic to those suffering from social phobia.",
"title": "Protein-source tryptophan as an efficacious treatment for social anxiety disorder: a pilot study."
},
{
"docid": "MED-3093",
"text": "BACKGROUND: Dietary intake of phosphorus is derived largely from protein sources and is a critical determinant of phosphorus balance in patients with chronic kidney disease. Information about the phosphorus content of prepared foods generally is unavailable, but it is believed to contribute significantly to the phosphorus burden of patients with chronic kidney disease. DESIGN: Analysis of dietary components. SETTING: We measured the phosphorus content of 44 food products, including 30 refrigerated or frozen precooked meat, poultry, and fish items, generally national brands. OUTCOMES: Measured and reported phosphorus content of foods. MEASUREMENTS: Phosphorus by using Association of Analytical Communities official method 984.27; protein by using Association of Analytical Communities official method 990.03. RESULTS: We found that the ratio of phosphorus to protein content in these items ranged from 6.1 to 21.5 mg of phosphorus per 1 g of protein. The mean ratio in the 19 food products with a label listing phosphorus as an additive was 14.6 mg/g compared with 9.0 mg/g in the 11 items without listed phosphorus. The phosphorus content of only 1 precooked food product was available in a widely used dietary database. LIMITATIONS: Results cannot be extrapolated to other products. Manufacturers also may alter the phosphorus content of foods at any time. Protein content was not directly measured for all foods. CONCLUSION: Better reporting of phosphorus content of foods by manufacturers could result in improved dietary phosphorus control without risk of protein malnutrition.",
"title": "Dietary phosphorus restriction in dialysis patients: potential impact of processed meat, poultry, and fish products as protein sources."
},
{
"docid": "MED-4353",
"text": "We have compared the effects of dietary soy protein and casein in diets low in cholesterol (less than 100 mg/d) and in diets enriched in cholesterol (500 mg/d) to examine whether the level of cholesterol intake affects the response of plasma lipoproteins to dietary proteins of plant and animal origin. Normal men and women consumed formula diets containing 20% of calories as soy protein or casein, 27% as fat and 53% as carbohydrate in 2 crossover studies. The dietary periods lasted for 31 days and were separated by a month-long interim period on self-chosen food. Following an initial reduction of plasma total cholesterol and low-density lipoprotein-cholesterol (LDL-C) levels on all diets, the plasma lipid and lipoprotein concentrations stabilized. On low-cholesterol diets the concentration of each of the major lipoprotein classes were similar during the soy and the casein dietary periods. On cholesterol-enriched diets, the concentration of LDL-C stabilized at a 16% lower level on soy protein than on the casein diet (p less than 0.02), while the concentration of high-density lipoprotein-cholesterol (HDL-C) was 16% higher (p less than 0.01). Since the difference in LDL-C (p less than 0.05) and in HDL-C (p less than 0.025) levels on casein and on soy protein diets were significantly greater on the high than on the low cholesterol intake, the findings indicate that the level of dietary cholesterol may determine whether plant and animal dietary proteins have similar or different effects on plasma LDL-C and HDL-C concentrations.",
"title": "Effects of dietary proteins on plasma lipoprotein levels in normal subjects: interaction with dietary cholesterol."
},
{
"docid": "MED-4408",
"text": "The influence of protein oxidation, as measured by the dinitrophenylhydrazine (DNPH) method, on colour and texture changes during chill storage (2 degrees C, 12days) of cooked burger patties was studied. Extracts from arbutus-berries (Arbutus unedoL., AU), common hawthorns (Crataegus monogynaL., CM), dog roses (Rosa caninaL., RC) and elm-leaf blackberries (Rubus ulmifoliusSchott., RU) were prepared, added to burger patties (3% of total weight) and evaluated as inhibitors of protein oxidation and colour and texture changes. Negative (no added extract, C) and positive control (added quercetin; 230mg/kg, Q) groups were also considered. The significant increase of protein carbonyls during chill storage of control burger patties reflect the intense oxidative degradation of the muscle proteins. Concomitantly, an intense loss of redness and increase of hardness was found to take place in burger patties throughout refrigerated storage. Most fruit extracts as well as Q significantly reduced the formation of protein carbonyls and inhibited colour and texture deterioration during chill storage. Likely mechanisms through which protein oxidation could play a major role on colour and texture changes during chill storage of burger patties are discussed. Amongst the extracts, RC was most suitable for use as a functional ingredient in processed meats since it enhanced oxidative stability, colour and texture properties of burger patties with no apparent drawbacks. Copyright 2010 Elsevier Ltd. All rights reserved.",
"title": "Protein oxidation in emulsified cooked burger patties with added fruit extracts: Influence on colour and texture deterioration during chill storage."
},
{
"docid": "MED-2978",
"text": "Diets high in protein have shown positive effects on short-term weight reduction and glycaemic control. However, the understanding of how dietary macronutrient composition relates to long-term risk of type 2 diabetes is limited. The aim of the present study was to examine intakes of macronutrients, fibre and protein sources in relation to incident type 2 diabetes. In total, 27 140 individuals, aged 45-74 years, from the population-based Malmö Diet and Cancer cohort, were included. Dietary data were collected with a modified diet history method, including registration of cooked meals. During 12 years of follow-up, 1709 incident type 2 diabetes cases were identified. High protein intake was associated with increased risk of type 2 diabetes (hazard ratio (HR) 1.27 for highest compared with lowest quintile; 95 % CI 1.08, 1.49; P for trend = 0.01). When protein consumption increased by 5 % of energy at the expense of carbohydrates (HR 1.20; 95 % CI 1.09, 1.33) or fat (HR 1.21; 95 % CI 1.09, 1.33), increased diabetes risk was observed. Intakes in the highest quintiles of processed meat (HR 1.16; 95 % CI 1.00, 1.36; P for trend = 0.01) and eggs (HR 1.21; 95 % CI 1.04, 1.41; P for trend = 0.02) were associated with increased risk. Intake of fibre-rich bread and cereals was inversely associated with type 2 diabetes (HR 0.84; 95 % CI 0.73, 0.98; P for trend = 0.004). In conclusion, results from the present large population-based prospective study indicate that high protein intake is associated with increased risk of type 2 diabetes. Replacing protein with carbohydrates may be favourable, especially if fibre-rich breads and cereals are chosen as carbohydrate sources.",
"title": "High intakes of protein and processed meat associate with increased incidence of type 2 diabetes."
},
{
"docid": "MED-825",
"text": "BACKGROUND: Some evidence has suggested that a diet with a higher ratio of protein to carbohydrates has metabolic advantages in the treatment of polycystic ovary syndrome (PCOS). OBJECTIVE: The objective of this study was to compare the effect of a high-protein (HP) diet to a standard-protein (SP) diet in women with PCOS. DESIGN: A controlled, 6-mo trial was conducted in 57 PCOS women. The women were assigned through rank minimization to one of the following 2 diets without caloric restriction: an HP diet (>40% of energy from protein and 30% of energy from fat) or an SP diet (<15% of energy from protein and 30% of energy from fat). The women received monthly dietary counseling. At baseline and 3 and 6 mo, anthropometric measurements were performed, and blood samples were collected. RESULTS: Seven women dropped out because of pregnancy, 23 women dropped out because of other reasons, and 27 women completed the study. The HP diet produced a greater weight loss (mean: 4.4 kg; 95% CI: 0.3, 8.6 kg) and body fat loss (mean: 4.3 kg; 95% CI: 0.9, 7.6 kg) than the SP diet after 6 mo. Waist circumference was reduced more by the HP diet than by the SP diet. The HP diet produced greater decreases in glucose than did the SP diet, which persisted after adjustment for weight changes. There were no differences in testosterone, sex hormone-binding globulin, and blood lipids between the groups after 6 mo. However, adjustment for weight changes led to significantly lower testosterone concentrations in the SP-diet group than in the HP-diet group. CONCLUSION: Replacement of carbohydrates with protein in ad libitum diets improves weight loss and improves glucose metabolism by an effect that seems to be independent of the weight loss and, thus, seems to offer an improved dietary treatment of PCOS women.",
"title": "Effects of increased dietary protein-to-carbohydrate ratios in women with polycystic ovary syndrome."
},
{
"docid": "MED-4612",
"text": "Amino acids modulate the secretion of both insulin and glucagon; the composition of dietary protein therefore has the potential to influence the balance of glucagon and insulin activity. Soy protein, as well as many other vegan proteins, are higher in non-essential amino acids than most animal-derived food proteins, and as a result should preferentially favor glucagon production. Acting on hepatocytes, glucagon promotes (and insulin inhibits) cAMP-dependent mechanisms that down-regulate lipogenic enzymes and cholesterol synthesis, while up-regulating hepatic LDL receptors and production of the IGF-I antagonist IGFBP-1. The insulin-sensitizing properties of many vegan diets--high in fiber, low in saturated fat--should amplify these effects by down-regulating insulin secretion. Additionally, the relatively low essential amino acid content of some vegan diets may decrease hepatic IGF-I synthesis. Thus, diets featuring vegan proteins can be expected to lower elevated serum lipid levels, promote weight loss, and decrease circulating IGF-I activity. The latter effect should impede cancer induction (as is seen in animal studies with soy protein), lessen neutrophil-mediated inflammatory damage, and slow growth and maturation in children. In fact, vegans tend to have low serum lipids, lean physiques, shorter stature, later puberty, and decreased risk for certain prominent 'Western' cancers; a vegan diet has documented clinical efficacy in rheumatoid arthritis. Low-fat vegan diets may be especially protective in regard to cancers linked to insulin resistance--namely, breast and colon cancer--as well as prostate cancer; conversely, the high IGF-I activity associated with heavy ingestion of animal products may be largely responsible for the epidemic of 'Western' cancers in wealthy societies. Increased phytochemical intake is also likely to contribute to the reduction of cancer risk in vegans. Regression of coronary stenoses has been documented during low-fat vegan diets coupled with exercise training; such regimens also tend to markedly improve diabetic control and lower elevated blood pressure. Risk of many other degenerative disorders may be decreased in vegans, although reduced growth factor activity may be responsible for an increased risk of hemorrhagic stroke. By altering the glucagon/insulin balance, it is conceivable that supplemental intakes of key non-essential amino acids could enable omnivores to enjoy some of the health advantages of a vegan diet. An unnecessarily high intake of essential amino acids--either in the absolute sense or relative to total dietary protein--may prove to be as grave a risk factor for 'Western' degenerative diseases as is excessive fat intake.",
"title": "Vegan proteins may reduce risk of cancer, obesity, and cardiovascular disease by promoting increased glucagon activity."
},
{
"docid": "MED-2150",
"text": "Previous investigations, of adolescent diet recalled in adulthood, found lower risk for benign breast disease (BBD) with higher intakes of vegetable fat and nuts during high school. We investigate whether vegetable protein and fat, derived from diets reported during pre-adolescence and adolescence, are associated with subsequent risk for BBD in young women. The Growing Up Today Study includes 9,039 females, 9–15 years in 1996, who completed questionnaires annually through 2001, and then in 2003, 2005, 2007, and 2010. Food frequency questionnaires (1996–2001) obtained intake data on a variety of foods. Beginning in 2005, women (18–30 years) reported whether they had ever been diagnosed with BBD that was confirmed by breast biopsy (n = 112 cases). Logistic regression estimated associations between intakes of vegetable protein and fat and biopsy-confirmed BBD. Those individual foods that were the largest contributors of protein and fat in this cohort were also investigated. In analyses of intakes from 1996 through 1998, when our cohort was youngest, vegetable fat (OR = 0.72/(10 gm/day), 95 % CI 0.53–0.98; p = 0.04) was inversely associated with BBD risk. The greatest sources of vegetable fat and protein in these girls were peanut butter, peanuts, nuts, beans (beans, lentils, and soybeans), and corn. A daily serving of any one of these was associated with lower risk (OR = 0.32/(serv/day), 95 % CI 0.13–0.79; p = 0.01). Peanut butter (and nuts) at age 11 years was inversely associated with risk (p = 0.01). In analyses of intakes at age 14 years, vegetable protein was associated with lower BBD risk (OR = 0.64/(10 gm/day), 95 % CI 0.43–0.95; p = 0.03). A daily serving at 14 years of any one of the foods was associated with lower risk (OR = 0.34, 95 % CI 0.16–0.75; p = 0.01), as was peanut butter (and nuts) (p = 0.02). Girls with a family history of breast cancer had significantly lower risk if they consumed these foods or vegetable fat. In conclusion, consumption of vegetable protein, fat, peanut butter, or nuts by older girls may help reduce their risk of BBD as young women.",
"title": "Vegetable protein and vegetable fat intakes in pre-adolescent and adolescent girls, and risk for benign breast disease in young women"
},
{
"docid": "MED-1324",
"text": "Six noninsulin-dependent diabetic subjects received meals containing 25 g carbohydrate either as potato or as spaghetti. The meals were repeated with the addition of 25 g protein and with 25 g protein and 25 g fat. Blood glucose and insulin responses were measured for 4 h after the test meal. When carbohydrate was given alone, the blood glucose and serum insulin increments were higher for the potato meal. The addition of protein increased the insulin responses to both carbohydrates and slightly reduced the glycemic response to mashed potato (F = 2.04, p less than 0.05). The further addition of fat reduced the glycemic response to mashed potato (F = 14.63, p less than 0.001) without any change in the blood glucose response to spaghetti (F = 0.94, NS). The different responses to coingestion of protein and fat reduced the difference between the glycemic responses to the two carbohydrates.",
"title": "Differential effect of protein and fat ingestion on blood glucose responses to high- and low-glycemic-index carbohydrates in noninsulin-dependent d..."
},
{
"docid": "MED-1134",
"text": "BACKGROUND: The purpose of this article is to evaluate the impact of low protein and high fiber intakes on risk factors of stone recurrence in idiopathic calcium stone formers (ICSFs). METHODS: Ninety-six ICSFs were randomly assigned a low animal protein diet (< 10% of total energy), a high-fiber diet (> 25 g/day), or a usual diet (control group); all patients were recommended to increase their fluid intake. Their daily urine compositions were analyzed at baseline and at four months. Compliance with dietary recommendations was checked by validated food frequency questionnaires. Compliance with total and animal protein intakes was assessed by 24-hour urea and sulfate outputs, respectively. The nutritional intervention (oral instructions, written leaflet, phoning) and food assessment were carried out by a research dietitian. RESULTS: At baseline, diets and the daily urine composition did not differ between the three groups. At four months, while diets differed significantly, the 24-hour output of calcium and oxalate did not differ significantly within and between groups after adjustment for potential confounders (age, sex, and personal and family history of calcium stones) and baseline values. However, as many as 12 out of 31 ICSFs (95% CI, 22 to 58%) assigned to a low animal protein diet achieved a reduction in the urine urea excretion rate of more than 50 mmol/day and also exhibited a significant decrease in urinary calcium excretion that averaged 1.8 mmol/day. A significant correlation between urea and calcium outputs was observed only among patients with hypercalciuria. CONCLUSIONS: These results show that only ICSFs who markedly decrease their animal protein intake, especially those with hypercalciuria, can expect to benefit from dietary recommendations.",
"title": "Effects of low animal protein or high-fiber diets on urine composition in calcium nephrolithiasis."
},
{
"docid": "MED-4342",
"text": "OBJECTIVES: Diet composition has long been suspected to contribute to inflammatory bowel disease (IBD), but has not been thoroughly assessed, and has been assessed only in retrospective studies that are prone to recall bias. The aim of the present study was to evaluate the role of dietary macronutrients in the etiology of IBD in a large prospective cohort. METHODS: The Etude Épidémiologique des femmes de la Mutuelle Générale de l'Education Nationale cohort consists of women living in France, aged 40-65 years, and free of major diseases at inclusion. A self-administered questionnaire was used to record dietary habits at baseline. Questionnaires on disease occurrence and lifestyle factors were completed every 24 months. IBDs were assessed in each questionnaire until June 2005, and subsequently validated using clinical and pathological criteria. We estimated the association between nutrients or foods and IBD using Cox proportional hazards models adjusted for energy intake. RESULTS: Among 67,581 participants (705,445 person-years, mean follow-up since completion of the baseline dietary questionnaire 10.4 years), we validated 77 incident IBD cases. High total protein intake, specifically animal protein, was associated with a significantly increased risk of IBD, (hazards ratio for the third vs. first tertile and 95% confidence interval being 3.31 and 1.41-7.77 (P trend=0.007), and 3.03 and 1.45-6.34 (P trend=0.005) for total and animal protein, respectively). Among sources of animal protein, high consumption of meat or fish but not of eggs or dairy products was associated with IBD risk. CONCLUSIONS: High protein intake is associated with an increased risk of incident IBD in French middle-aged women.",
"title": "Animal protein intake and risk of inflammatory bowel disease: The E3N prospective study."
},
{
"docid": "MED-4352",
"text": "Changes in the concentration and composition of serum VLDL, LDL, and HDL were studied in rabbits transferred from Chow diets to cholesterol-free, semipurified diets containing casein or isolated soy protein. During the first week on the casein diet, there was a marked increase in LDL-cholesterol and these higher levels were maintained during the subsequent 3 weeks of the study. Similar but less marked changes were obtained with the soy protein diet. When the percent composition of the particles was determined, both VLDL and LDL had a higher proportion of cholesterol. Turnover studies indicated that the FCRs for radiolabelled VLDL and LDL were reduced in casein-fed animals compared to those fed soy protein. The elevated LDL levels in casein-fed rabbits were primarily due to a reduction in receptor-mediated catabolism of LDL-apo B. Receptor-independent removal in the two groups was similar. These studies show that the hypercholesterolemia in casein-fed rabbits, compared to those fed soy protein, is associated with cholesterol enrichment of LDL and impaired receptor-dependent removal of LDL-apo B.",
"title": "Effects of dietary protein on composition and metabolism of plasma lipoproteins in rabbits."
},
{
"docid": "MED-4898",
"text": "We examined consumption of animal foods, protein and calcium in relation to risk of prostate cancer among 142 251 men in the European Prospective Investigation into Cancer and Nutrition. Associations were examined using Cox regression, stratified by recruitment centre and adjusted for height, weight, education, marital status and energy intake. After an average of 8.7 years of follow-up, there were 2727 incident cases of prostate cancer, of which 1131 were known to be localised and 541 advanced-stage disease. A high intake of dairy protein was associated with an increased risk, with a hazard ratio for the top versus the bottom fifth of intake of 1.22 (95% confidence interval (CI): 1.07–1.41, Ptrend=0.02). After calibration to allow for measurement error, we estimated that a 35-g day−1 increase in consumption of dairy protein was associated with an increase in the risk of prostate cancer of 32% (95% CI: 1–72%, Ptrend=0.04). Calcium from dairy products was also positively associated with risk, but not calcium from other foods. The results support the hypothesis that a high intake of protein or calcium from dairy products may increase the risk for prostate cancer.",
"title": "Animal foods, protein, calcium and prostate cancer risk: the European Prospective Investigation into Cancer and Nutrition"
},
{
"docid": "MED-1440",
"text": "Aging and metabolism-related disorders are risk factors for Alzheimer disease (AD). Since sirtuins may increase the lifespan through regulation of cellular metabolism, we compared the concentration of sirtuin 1 (SIRT1) in the brains of AD patients (n = 19) and controls (n = 22) using Western immunoblots and in situ hybridization. We report a significant reduction of SIRT1 (mRNA: −29%; protein: −45%) in the parietal cortex of AD patients, but not in the cerebellum. Further analyses in a second cohort of 36 subjects confirmed that cortical SIRT1 was decreased in the cortex of AD patients but not in individuals with mild cognitive impairment. SIRT1 mRNA and its translated protein correlated negatively with the duration of symptoms (mRNA: r2 = −0.367; protein: r2 = −0.326) and the accumulation of paired helical filament tau (mRNA: r2 = −0.230; protein: r2 = −0.119), but weakly with insoluble amyloid-β(Aβ42 (mRNA: r2 = −0.090; protein: r2 = −0.072). A significant relationship between SIRT1 levels and global cognition scores proximate to death was also found (r2 = +0.09; p = 0.049). In contrast, cortical SIRT1 levels remained unchanged in a triple-transgenic animal model of AD. Collectively, our results indicate that loss of SIRT1 is closely associated with the accumulation of Aβ and tau in the cerebral cortex of patients with AD.",
"title": "SIRT1 Decrease Parallels the Accumulation of tau in Alzheimer Disease"
},
{
"docid": "MED-2315",
"text": "Background The word selectivity describes a drug's ability to affect a particular cell population in preference to others. As part of the current state of art in the search for new therapeutic agents, the property of selectivity is a mode of action thought to have a high degree of desirability. Consequently there is a growing activity in this area of research. Selectivity is generally a worthy property in a drug because a drug having high selectivity may have a dramatic effect when there is a single agent that can be targeted against the appropriate molecular-driver involved in the pathogenesis of a disease. An example is chronic myeloid leukemia (CML). CML has a specific chromosomal abnormality, the Philadelphia chromosome, that results in a single gene that produces an abnormal protein Discussion There is a burgeoning understanding of the cellular mechanisms that control the etiology and pathogeneses of diseases. This understanding both enables and motivates the development of drugs that induce a specific action in a selected cell population; i.e., a targeted treatment. Consequently, drugs that can target distinct molecular targets involved in pathologic/pathogenetic processes, or signal-transduction pathways, are being developed. However, in most cases, diseases involve multiple abnormalities. A disease may be associated with more than one dysfunctional protein and these may be out-of-balance with each other. Likewise a drug might strongly target a protein that shares a similar active domain with other proteins. A drug may also target pleiotropic cytokines, or other proteins that have multi-physiological functions. In this way multiple normal cellular pathways can be simultaneously influenced. Long term experience with drugs supposedly designed for only a single target, but which unavoidably involve other functional effects, is uncovering the fact that molecular targeting is not medically flawless. Summary We contend that an ideal drug may be one whose efficacy is based not on the inhibition of a single target, but rather on the rebalancing of the several proteins or events, that contribute to the etiology, pathogeneses, and progression of diseases, i.e., in effect a promiscuous drug. Ideally, if this could be done at minimum drug concentration, side effects could be minimized. Corollaries to this argument are that the growing fervor for researching truly selective drugs may be imprudent when considering the totality of responses; and that the expensive screening techniques used to discover these, may be both medically and financially inefficient.",
"title": "Promiscuous drugs compared to selective drugs (promiscuity can be a virtue)"
},
{
"docid": "MED-2603",
"text": "FAS-associated protein with death domain (FADD) is the key adaptor protein transmitting apoptotic signals mediated by the main death receptors (DRs). Besides being an essential instrument in cell death, FADD is also implicated in proliferation, cell cycle progression, tumor development, inflammation, innate immunity, and autophagy. Recently, many of these new functions of FADD were shown to be independent of DRs. Moreover, FADD function is dictated by protein localization and phosphorylation state. Thus, FADD is a crucial and unique controller of many essential cellular processes. The full understanding of the networks dictating the ultimate function of FADD may provide a new paradigm for other multifaceted proteins. Copyright 2010 Elsevier Ltd. All rights reserved.",
"title": "FADD: a regulator of life and death."
},
{
"docid": "MED-2136",
"text": "Prostate cancer (PCa) is dependent on androgen receptor signaling and aberrations of the PI3K-Akt-mTORC1 pathway mediating excessive and sustained growth signaling. The nutrient-sensitive kinase mTORC1 is upregulated in nearly 100% of advanced human PCas. Oncogenic mTORC1 signaling activates key subsets of mRNAs that cooperate in distinct steps of PCa initiation and progression. Epidemiological evidence points to increased dairy protein consumption as a major dietary risk factor for the development of PCa. mTORC1 is a master regulator of protein synthesis, lipid synthesis and autophagy pathways that couple nutrient sensing to cell growth and cancer. This review provides evidence that PCa initiation and progression are promoted by cow´s milk, but not human milk, stimulation of mTORC1 signaling. Mammalian milk is presented as an endocrine signaling system, which activates mTORC1, promotes cell growth and proliferation and suppresses autophagy. Naturally, milk-mediated mTORC1 signaling is restricted only to the postnatal growth phase of mammals. However, persistent consumption of cow´s milk proteins in humans provide highly insulinotropic branched-chain amino acids (BCAAs) provided by milk´s fast hydrolysable whey proteins, which elevate postprandial plasma insulin levels, and increase hepatic IGF-1 plasma concentrations by casein-derived amino acids. BCAAs, insulin and IGF-1 are pivotal activating signals of mTORC1. Increased cow´s milk protein-mediated mTORC1 signaling along with constant exposure to commercial cow´s milk estrogens derived from pregnant cows may explain the observed association between high dairy consumption and increased risk of PCa in Westernized societies. As well-balanced mTORC1-signaling plays an important role in appropriate prostate morphogenesis and differentiation, exaggerated mTORC1-signaling by high cow´s milk consumption predominantly during critical growth phases of prostate development and differentiation may exert long-term adverse effects on prostate health. Attenuation of mTORC1 signaling by contemporary Paleolithic diets and restriction of dairy protein intake, especially during mTORC1-dependent phases of prostate development and differentiation, may offer protection from the most common dairy-promoted cancer in men of Western societies.",
"title": "The impact of cow's milk-mediated mTORC1-signaling in the initiation and progression of prostate cancer"
},
{
"docid": "MED-4852",
"text": "OBJECTIVES: A dietary link to rheumatoid arthritis (RA) has been suspected and an influence on arthritic symptoms by different diets has been reported. Our primary aim was to record the self-experienced adverse food reactions in patients with RA. A secondary aim was to relate self-experienced adverse reactions to dairy produce and wheat to the local mucosal reactivity observed after rectal challenge with cow's milk protein (CM) and wheat gluten. METHODS: A questionnaire about self-experienced adverse reaction to food was sent to 347 RA patients. Rectal challenge with CM and gluten was performed in 27 of these patients and in healthy controls (n = 18). After a 15-h challenge the mucosal production of nitric oxide (NO) and the mucosal release of myeloperoxidase (MPO) and eosinophil cationic protein (ECP) were measured by using the mucosal patch technique. RESULTS: Twenty-seven per cent of the RA patients reported food intolerance (FI) to various foods, and in particular to CM, meat, and wheat gluten. Strong mucosal reactivity to CM was observed in 11% of the patients. Moderately increased mucosal reactivity to CM and gluten was found in 22% and 33%, respectively, of the patients. No relationship was found between self-experienced adverse reactions to CM or gluten and mucosal reactivity to these proteins. CONCLUSIONS: Perceived FI is reported frequently by RA patients, with a prevalence similar to that reported previously in the general population. Mucosal reactivity to CM and gluten is seen in a minor fraction of RA patients and is not related to the frequently perceived intolerance to these proteins.",
"title": "Self-reported food intolerance and mucosal reactivity after rectal food protein challenge in patients with rheumatoid arthritis."
}
] |
7085
|
Canadian Citizen and Non Resident for tax purposes
|
[
{
"docid": "456968",
"text": "However, you might have to pay taxes on capital gains if these stocks were acquired during your prior residency.",
"title": ""
}
] |
[
{
"docid": "518624",
"text": "\"The other answer has mentioned \"\"factual resident\"\", and you have raised the existence of a U.S./Canada tax treaty in your comment, and provided a link to a page about determining residency. I'd like to highlight part of the first link: You are a factual resident of Canada for tax purposes if you keep significant residential ties in Canada while living or travelling outside the country. The term factual resident means that, although you left Canada, you are still considered to be a resident of Canada for income tax purposes. Notes If you have established ties in a country that Canada has a tax treaty with and you are considered to be a resident of that country, but you are otherwise a factual resident of Canada, meaning you maintain significant residential ties with Canada, you may be considered a deemed non-resident of Canada for tax purposes. [...] I'll emphasize that \"\"considered to be a resident of Canada for income tax purposes\"\" means you do need to file Canadian income tax returns. The Notes section does indicate the potential treaty exemption that you mentioned, but it is only a potential exemption. Note the emphasis (theirs, not mine) on the word \"\"may\"\" in the last paragraph above. Please don't assume \"\"may\"\" is necessarily favorable with respect to your situation. The other side of the \"\"may\"\" coin is \"\"may not\"\". The Determining your residency status page you mentioned in your comment says this: If you want the Canada Revenue Agency's opinion on your residency status, complete either Form NR74, Determination of Residency Status (Entering Canada) or Form NR73, Determination of Residency Status (Leaving Canada), whichever applies, and send it to the International and Ottawa Tax Services Office. To get the most accurate opinion, provide as many details as possible on your form. So, given your ties to Canada, I would suggest that until and unless you have obtained an opinion from the Canada Revenue Agency on your tax status, you would be making a potentially unsafe assumption if you yourself elect not to file your Canadian income tax returns based on your own determination. You could end up liable for penalties and interest if you don't file while you are outside of Canada. Tax residency in Canada is not a simple topic. For instances, let's have a look at S5-F1-C1, Determining an Individual’s Residence Status. It's a long page, but here's one interesting piece: 1.44 The Courts have stated that holders of a United States Permanent Residence Card (otherwise referred to as a Green Card) are considered to be resident in the United States for purposes of paragraph 1 of the Residence article of the Canada-U.S. Tax Convention. For further information, see the Federal Court of Appeal's comments in Allchin v R, 2004 FCA 206, 2004 DTC 6468. [...] ... whereas you are in the U.S. on a TN visa, intended to be temporary. So you wouldn't be exempt just on the basis of your visa and the existence of the treaty. The CRA would look at other circumstances. Consider the \"\"Centre of vital interests test\"\": Centre of vital interests test [...] “If the individual has a permanent home in both Contracting States, it is necessary to look at the facts in order to ascertain with which of the two States his personal and economic relations are closer. Thus, regard will be had to his family and social relations, his occupations, his political, cultural or other activities, his place of business, the place from which he administers his property, etc. The circumstances must be examined as a whole, but it is nevertheless obvious that considerations based on the personal acts of the individual must receive special attention. If a person who has a home in one State sets up a second in the other State while retaining the first, the fact that he retains the first in the environment where he has always lived, where he has worked, and where he has his family and possessions, can, together with other elements, go to demonstrate that he has retained his centre of vital interests in the first State.” [emphasis on last sentence is mine] Anyway, I'm acquainted with somebody who left Canada for a few years to work abroad. They assumed that living in the other country for that length of time (>2 years) meant they were non-resident here and so did not have to file. Unfortunately, upon returning to Canada, the CRA deemed them to have been resident all that time based on significant ties maintained, and they subsequently owed many thousands of dollars in back taxes, penalties, and interest. If it were me in a similar situation, I would err on the side of caution and continue to file Canadian income taxes until I got a determination I could count on from the people that make the rules.\"",
"title": ""
},
{
"docid": "594784",
"text": "If you're a US citizen/resident - you pay taxes on your worldwide income regardless of where you live. The logic is that Americans generally don't agree to the view that there's more than one country in the world. If you're non-US person, not physically present in the US, and provide contract work for a US employer - you generally don't pay taxes in the US. The logic is that the US doesn't actually have any jurisdiction over that money, you didn't earn it in the US. That said, your employer might withheld tax and remit it to the IRS, and you'll have to chase them for refund. If you receive income from the US rental property or dividends from a US company - you pay income tax to the US on that income, and then bargain with your home tax authority on refunds of the difference between what you paid in the US and what you should have paid at home. You can also file non-resident tax return in the US to claim what you have paid in excess. The logic is that the money sourced in the US should be taxed in the US. You earned that money in the US. There are additional rules to more specific situation, and there are also bilateral treaties between countries (including a US-Canadian treaty) that supersede national laws. Bottom line, not only that each country has its own laws, there are also different laws for different situations, and if some of the international treaties apply to you - it further complicates the situation. If something is not clear - get a professional advice form a tax accountant licensed in the relevant jurisdictions (in your case - any of the US states, and the Canadian province where you live).",
"title": ""
},
{
"docid": "347186",
"text": "Tax liability in US: You would need to determine if you are a resident alien or non resident alien. Resident alien are taxed normally as per US citizens. For the annual remuneration you have quoted it would be in the range of 25%. Refer http://www.moneychimp.com/features/tax_brackets.htm To determine if you are resident alien or non resident alien, you need to be present for certain period in US. There is also an exemption even if you meet this you can still be treated as non resident alien if your tax home is outside US [India in this case] Refer to the link for details to determine your category, the durations are for number of days in financial year, hence it matters when you are in US and the exact durations. http://www.irs.gov/taxtopics/tc851.html Also note that if you are assessed as resident alien, even the income from India will be taxed in US unless you declare there is no income in India. Tax liability in India: The tax liability in India would be depending on your NRI status. This again is tied to the financial year and the number of days you are in country. While the year you are going out of India you need to be away for atleast 183 days for you be considred are NRI. So if you are treated as Indian resident, you would have to pay tax in India on entire income. In the worst case, depending on the period you travel and the dates you travel, you could get classified as citizen in US as well as India and have to pay tax at both places. India and US do not have a dual tax avoidance treaty for individuals. Its there for certain category like small business and certain professions like teacher, research etc.",
"title": ""
},
{
"docid": "272173",
"text": "Assuming you are Indian Citizen / Resident for Tax purposes. Your friend in US Citizen / Resident for tax purposes. As you are borrowing these funds and returning, this would NOT be treated as Gift but as Loan. Ensure that you have the right documentation in place. There is no tax when you receive the funds/loan or rebate when you pay back the loan. From India FEMA (Foreign Exchange Management Act) point of view, if you take loan from friends, you cannot by default repatriate funds. You have to take special permission to repatriate the funds out of India.",
"title": ""
},
{
"docid": "570639",
"text": "\"Transferring the money or keeping it in US does has no effect on taxes. Your residency status has. Assuming you are Resident Alien in US for tax purpose and have paid the taxes to IRS and you are \"\"Non-Resident\"\" Indian for tax purposes in India as you are more than 182 outside India. How would it effect my Tax in US and India If you are \"\"Non-Resident\"\" in India for tax purposes, there is no tax liability of this in India. I have transferred an amount of approx 15-20k$ to Indian Account (not NRE) By RBI regulation, if you are \"\"Non-Resident\"\" then you should get your savings account converted to \"\"NRO\"\". You may not may not choose to open an NRE account. To keep the paper work clear it helps that you open an NRE account in India. Any investment needed ? Where do i need to declare if any ? These are not relevant. Note any income generated in India, i.e. interest in Savings account / FDs / Rent etc; taxes need to be paid in India and declared in US and taxes paid in US as well. There is some relief under DTAA. There are quite a few question on this site that will help you clarify what needs to be done.\"",
"title": ""
},
{
"docid": "575899",
"text": "Found a great article (with bibliography) that covers taxation on investment activity by non resident aliens - even covers the special 15% tax on dividends for Canadian residents. It's (dividend tax rate) generally 30% for other NRAs (your 2nd question). And it confirmed my suspicion that there are no capital gains taxes for NRAs. (1st Q) Source: http://invest-faq.com/articles/tax-non-us-nat.html",
"title": ""
},
{
"docid": "352266",
"text": "Canada doesn't tax non-residents on income earned/incurred outside of Canada. So, your sister should start with this page to determine the residency status. If she is indeed determined to be non-resident - she should look here to see her obligations. If all she earns she earns outside of Canada - her obligations will be very little, if at all. This is similar to almost any other country in the world, with the notable exception of the United States of America. US citizens are taxed regardless of their residency status, everywhere in the world on worldwide income (unless tax treaty says otherwise).",
"title": ""
},
{
"docid": "214690",
"text": "Gifts from your parents are not treated as income for tax purposes. You should not include that in your subsidy calculation. If you are here on a student-visa and have been in the US for less than 5 years, then you are considered a non-resident alien, and you are not required to buy a qualified plan through the insurance marketplace. You might be able to get a cheaper student plan through your school, but the subsidy might be enough that it's still worth it when calculated correctly. If you are a resident-alien or you are a citizen of the US, then you are required to get coverage, though you can choose not to purchase coverage and pay the tax for not having creditable coverage. That tax cannot be collected by the IRS unless you have already had federal tax withheld. They can only confiscate your tax return money to recoup that money. I don't have enough information to recommend one way or the other what you should do, but I would bet that if you recalculated your subsidy without including your parents income it would cover the majority of the cost. You should also consider applying for Medicaid if you meet the eligibility requirements in your state.",
"title": ""
},
{
"docid": "298796",
"text": "The finance team from your company should be able to advise you. From what I understand you are Indian Citizen for Tax purposes. Any income you receive globally is taxable in India. In this specific case you are still having a Employee relationship with your employer and as such the place of work does not matter. You are still liable to pay tax in India on the salary. If you are out of India for more than 182 days, you can be considered as Non-Resident from tax point of view. However this clause would not be of any benefit to you as are having a Employee / Employer relationship and being paid in India. Edit: This is only about the India portion of taxes. There maybe a UK protion of it as well, plus legally can you work and your type of Visa in UK may have a bearing on the answer",
"title": ""
},
{
"docid": "228445",
"text": "Yes, you have to file a tax return in Canada. Non residents that have earned employment income in Canada are required to file a Canadian personal income tax return. Usually, your employer will have deducted sufficient taxes from your pay-cheques, resulting in a tax refund upon filing your Canadian tax return. You will also receive a tax credit on your US tax return for taxes paid in Canada.",
"title": ""
},
{
"docid": "457455",
"text": "It essentially works the same. Some states don't have any income taxes at all (like Florida or Wyoming), some only tax income derived in the state, and some tax worldwide income (like New York or California), similarly to the Federal income taxes. However, if you're living abroad (i.e.: you're a citizen or resident of a foreign country and you live there), you're not considered resident by most of the states (check with your state for specific definitions) for most, if not all, the time of your residency abroad. In such case - you don't pay state taxes, only Federal. You have to remember that foreign income exclusion doesn't apply to the income from your 401k, so you pay the taxes as if you're in the US. You can not use foreign taxes credit as well (but depending on the tax treaty with the country you're moving to, your 401k income might not be taxable there). In some cases you may end up with double taxation: US will tax your 401k income as you're a US citizen and the income is derived from the US sources, and the foreign country will tax the income based on its own laws. This is not a tax advice, and this answer was not intended or written to be used, and it cannot be used by any taxpayer, for the purpose of avoiding penalties that may be imposed on the taxpayer.",
"title": ""
},
{
"docid": "241048",
"text": "Taxability depends on your tax residency status. Assuming you are non-resident Indian for tax purposes, then your income is non taxable in India. If you keep the money in Saudi or transfer to India it would be same and non taxable",
"title": ""
},
{
"docid": "360773",
"text": "Though non-resident Indians (NRIs) earn their living abroad, their obligation to file tax returns in India doesn't end. With the July 31 deadline for filing returns barely a month away, NRIs need to gear up to file their return if they have income in India that exceeds the basic exemption limit. How to Determine tax residency status: An NRI first needs to determine his tax residency status, that is, whether he falls in the category of resident or non-resident Indian (NRI) for tax purposes. While there may be no ambiguity regarding the status of an NRI who has lived abroad for a long time, those who have moved abroad recently or have returned to India after a long stay abroad need to ascertain their residency status properly.",
"title": ""
},
{
"docid": "475115",
"text": "Per the IRS instructions on filing as Head of Household as a Citizen Living Abroad, if you choose to file only your own taxes, and you qualify for Head of Household without them, the IRS does not consider you married: If you are a U.S. citizen married to a nonresident alien you may qualify to use the head of household tax rates. You are considered unmarried for head of household purposes if your spouse was a nonresident alien at any time during the year and you do not choose to treat your nonresident spouse as a resident alien. However, your spouse is not a qualifying person for head of household purposes. You must have another qualifying person and meet the other tests to be eligible to file as a head of household. As such, you could file as Married Filing Separately (if you have no children) or Head of Household (if you have one or more children, a parent, etc. for whom you paid more than half of their upkeep - see the document for more information). You also may choose to file as Married Filing Jointly, if it benefits you to do so (it may, if she earns much less than you). See the IRS document Nonresident Spouse Treated As Resident for more information. If you choose to treat her as a resident, then you must declare her worldwide income. In some circumstances this will be beneficial for you, if you earn substantially more than her and it lowers your tax rate overall to do so. Married Filing Separately severely limits your ability to take some deductions and credits, so it's well worth seeing which is better.",
"title": ""
},
{
"docid": "367562",
"text": "I can only answer about the U.S. For question 2, I believe the answer is no. If you are a non-resident alien for tax purposes, then only income connected to the U.S. is reported as income on the tax return. Unless there were any non-deductible contributions to your pre-tax IRAs, when you convert to Roth IRA, the entire amount of the conversion is added to your income. So the tax consequence is the same as if you had that much additional U.S. income. If you are a non-resident alien with no other income in the U.S., then the income you have to report on your U.S. tax return will basically consist of the conversion. Non-resident aliens do not have a standard deduction. However, all people have a personal exemption. If we take 2013 as an example, the exemption is $3900 per person. We will assume that you will file as single or married filing separately (non-resident aliens cannot file as married filing jointly). The first $3900 of income is covered by the exemption, and is not counted in taxable income. For single and MFS, the next $8925 of income is taxed at 10%, then next $27325 of income is taxed at 15%, and so on. So if you convert less than the personal exemption amount every year ($3900 in 2013), then in theory you do not pay any taxes. If you convert a little bit more, then some of the conversion will be taxed at 10%, etc.",
"title": ""
},
{
"docid": "30343",
"text": "\"You've asked a number of questions. I can answer a few. I've quoted your question before each answer. What are the ins and outs of a foreigner like myself buying rental property in Canada? This is a pretty broad question which can address location, finances, basic suggestions etc. Here's some things to consider: Provincial considerations: Some ins and outs will depend on what province you are considering and what area in that Province. If you plan on owning in Montreal, for example, that's in the province of Quebec and that means you (or someone) will need to be able to operate in the French language. There are other things that might be different from province to province. See stat info below. Canadian vs. US Dollar: Now might be a great time to buy property in Canada since the Canada dollar is weak right now. To give you an idea, at a non-cash rate of 1.2846, a little over $76,000 US will get you over $100k Canadian. That's using the currency converter at rbcroyalbank.com. Taxes for non-resident rental property owners: According to the T4144 Income Tax Guide for Electing Under Section 216 – 2015: \"\"When you receive rental income from real or immovable property in Canada, the payer, such as the tenant or a property manager, has to withhold non-resident tax at the rate of 25% on the gross rental income paid or credited to you. The payer has to pay us the tax on or before the 15th day of the month following the month the rental income is paid or credited to you.\"\" If you prefer to send a separate Canadian tax return, you can choose to elect under section 216 of the Income Tax Act. A benefit of this way is that \"\"electing under section 216 allows you to pay tax on your net Canadian-source rental income instead of on the gross amount. If the non-resident tax withheld by the payer is more than the amount of tax payable calculated on your section 216 return, [they] will refund the excess to you.\"\" You can find this guide at Canada Revenue's site: http://www.cra-arc.gc.ca/E/pub/tg/t4144/README.html Stats: A good place for stats is the Canada Mortgage and Housing Corporation (CMHC). So, if you are interesting in vacancy rates for example, you can see a table that will show you that the vacancy rate in Ontario is 2.3% and in British Columbia it's 1.5%. However, in New Brunswick it's 8%. The rate for metropolitan areas across Canada is 2.8%. If you want to see or download this table showing the vacancy rates by province and also by metropolitan areas, go to the Canada Mortgage and Housing Corporation site http://www.cmhc.ca/housingmarketinformation/. You can get all sorts of housing information, reports and market information there. I've done well with Condos/Town-homes and would be interested in the same thing over there. Is it pretty much all the same? See the stat site mentioned above to get market info about condos, etc. What are the down payment requirements? For non-owner occupied properties, the down payment is at least 20%. Update in response to comments about being double taxed: Regarding being taxed on income received from the property, if you claim the foreign tax credit you will not be double taxed. According to the IRS, \"\"The foreign tax credit intends to reduce the double tax burden that would otherwise arise when foreign source income is taxed by both the United States and the foreign country from which the income is derived.\"\" (from IRS Topic 856 - Foreign Tax Credit) About property taxes: From my understanding, these would not be claimed for the foreign tax credit but can be deducted as business expenses. There are various exceptions and stipulations based on your circumstance, so you need to read Publication 856 - Foreign Tax Credit for Individuals. Here's an excerpt: \"\"In most cases, only foreign income taxes qualify for the foreign tax credit. Other taxes, such as foreign real and personal property taxes, do not qualify. But you may be able to deduct these other taxes even if you claim the foreign tax credit for foreign income taxes. In most cases, you can deduct these other taxes only if they are expenses incurred in a trade or business or in the production of income. However, you can deduct foreign real property taxes that are not trade or business expenses as an itemized deduction on Schedule A (Form 1040).\"\" Disclaimers: Sources: IRS Topic 514 Foreign Tax Credit and Publication 856 Foreign Tax Credit for Individuals\"",
"title": ""
},
{
"docid": "259602",
"text": "I can't give you a specific answer because I'm not a tax accountant, so you should seek advice from a tax professional with experience relevant to your situation. This could be a complicated situation. That being said, one place you could start is the Canada Revenue Agency's statement on investment income, which contains this paragraph: Interest, foreign interest and dividend income, foreign income, foreign non-business income, and certain other income are all amounts you report on your return. They are usually shown on the following slips: T5, T3, T5013, T5013A To avoid double taxation, Canada and the US almost certainly have a foreign tax treaty that ensures you are only taxed in your country of residence. I'm assuming you're a resident of Canada. Also, this page states that: If you received foreign interest or dividend income, you have to report it in Canadian dollars. Use the Bank of Canada exchange rate that was in effect on the day you received the income. If you received the income at different times during the year, use the average annual exchange rate. You should consult a tax professional. I'm not a tax professional, let alone one who specializes in the Canadian tax system. A professional is the only one you should trust to answer your question with 100% accuracy.",
"title": ""
},
{
"docid": "481601",
"text": "In theory, when you obtained ownership of your USD cash as a Canadian resident [*resident for tax purposes, which is generally a quicker timeline than being resident for immigration purposes], it is considered to have been obtained by you for the CAD equivalent on that date. For example if you immigrated on Dec 31, 2016 and carried $10k USD with you, when the rate was ~1.35, then Canada deems you to have arrived with $13.5k CAD. If you converted that CAD to USD when the rate was 1.39, you would have received 13.9k CAD, [a gain of $400 to show as income on your tax return]. Receiving the foreign inheritances is a little more complex; those items when received may or may not have been taxable on that day. However whether or not they were taxable, you would calculate a further gain as above, if the fx rate gave you more CAD when you ultimately converted it. If the rate went the other way and you lost CAD-value, you may or may not be able to claim a loss. If it was a small loss, I wouldn't bother trying to claim it due to hassle. If it's a large loss, I would be very sure to research thoroughly before claiming, because something like that probably has a high chance of being audited.",
"title": ""
},
{
"docid": "84528",
"text": "\"Tax US corporate \"\"persons (citizens)\"\" under the same regime as US human persons/citizens, i.e., file/pay taxes on all income earned annually with deductions for foreign taxes paid. Problem solved for both shareholders and governments. [US Citizens and Resident Aliens Abroad - Filing Requirements](https://www.irs.gov/individuals/international-taxpayers/us-citizens-and-resident-aliens-abroad-filing-requirements) >If you are a U.S. citizen or resident alien living or traveling outside the United States, **you generally are required to file income tax returns, estate tax returns, and gift tax returns and pay estimated tax in the same way as those residing in the United States.** Thing is, we know solving this isn't the point. It is to misdirect and talk about everything, but the actual issues, i.e., the discrepancy between tax regimes applied to persons and the massive inequality it creates in tax responsibility. Because that would lead to the simple solutions that the populace need/crave. My guess is most US human persons would LOVE to pay taxes only on what was left AFTER they covered their expenses.\"",
"title": ""
},
{
"docid": "235266",
"text": "In the general case if you have income coming in from a foreign source you need to declare it on your Canadian tax form, and nominally pay tax on it. However Canada has a tax agreement with the UK to ensure that you are not taxed twice. You also declare how much tax you have paid to the UK, and that is deducted from your Canadian tax bill. You may need to consult a tax professional, or maybe just read the Revenue Canada website to get the details. If you are holding this money for a friend, then you may find that this does not count as income to you. If you are getting it transferred to you in Canada, and then immediately passed on to your friend, it probably doesn't count as income (though again a tax professional will probably be helpful). This would mean you don't have to pay Canadian tax. But it's also a bummer because you've paid UK tax, which you might also have avoided, and you can't get that back without a lot of form filling. If this is going to be an ongoing situation, and the amount is significant, then you might look at getting your friend's money (and any you have in a UK account yourself) transferred to an offshore account, where UK tax is not automatically deducted. Most UK banks will do this for non-UK residents.",
"title": ""
},
{
"docid": "288993",
"text": "To build a US credit record, you need a Social Security Number (SSN), which is now not available for most non-residents. An alternative is an ITIN number, which is now available to non-residents only if they have US income giving a reason to file a US tax return (do you really want to get into all that...). Assuming you did have a reason to get a ITIN (one reason would be if you sold some ebooks via Amazon US, and need a withholding refund under the tax treaty), then recent reports on Flyertalk give mixed results on whether it's possible to get a credit card with an ITIN, and whether that would build a credit record. It does sound possible in some cases. A credit record in any other country would not help. You would certainly need a US address, and banks are increasingly asking for a physical address, rather than just a mailbox. Regardless, building this history would be of limited benefit to you if you later became a US resident, at that point you would be eligible for a new SSN (different from the ITIN) and have to largely start again. If getting a card is the aim, rather than the credit record, you may find some banks that will offer a secured card (or a debit card), to non-residents, especially in areas with lots of Canadian visitors (border, Florida, Arizona). You'd find it a lot easier with a US address though, and you'd need to shop around a lot of banks in person until you find one with the right rules. Most will simply avoid anyone without an SSN.",
"title": ""
},
{
"docid": "265861",
"text": "This answer applies only to corporation tax, not income tax. Different things, income tax is much higher. 12.5% is the low rate for corporation tax. The standard rate is 25%. Or if you're Apple 0%. Like many countries Ireland will only consider you eligible for the low rate of corporation tax if you (your Irish company) can demonstrably prove yourself resident in Ireland. This is more than just address, and you must be able to evidence that your staff work there, your directors are both European Economic Area citizens and have their board meetings in Ireland, and most importantly that they run the company from Ireland, etc. If you're a one man corporation, unless you want to live in Ireland, it's not going to work. Referring to the Irish government's website: The term 'residence' was not, until recently, defined in law. The general rule was that companies, whose 'central management and control' was exercised in the State, were treated as resident here. This rule or test emerged as a result of judicial decisions set down in case law. Factors to be taken into account in establishing where the company's central management and control lie include, for example, where the important questions of company policy are determined, where the majority of directors reside, where the negotiation of major contracts is undertaken and where the company's head office is located. Long story short: An Irish incorporated company is not treated as Irish resident for tax purposes if it is a 'relevant company' ... A Relevant Company is a company that ... is ultimately controlled by persons resident in the EU or in a country with which Ireland has concluded a double taxation treaty",
"title": ""
},
{
"docid": "141458",
"text": "\"Not really, no. The assumption you're making—withdrawals from a corporation are subject to \"\"[ordinary] income tax\"\"—is simplistic. \"\"Income tax\"\" encompasses many taxes, some more benign than others, owing to credits and exemptions based on the kind of income. Moreover, the choices you listed as benefits in the sole-proprietor case—the RRSP, the TFSA, and capital gains treatment for non-registered investments—all remain open to the owner of a small corporation ... the RRSP to the extent that the owner has received salary to create contribution room. A corporation can even, at some expense, establish a defined benefit (DB) pension plan and exceed individual RRSP contribution limits. Yes, there is a more tax-efficient way for small business owners to benefit when it comes time to retirement. Here is an outline of two things I'm aware of: If your retirement withdrawals from your Canadian small business corporation would constitute withdrawal from the corporation's retained earnings (profits), i.e. income to the corporation that had already been subject to corporate income tax in prior years, then the corporation is able to declare such distributions as dividends and issue you a T5 slip (Statement of Investment Income) instead of a T4 slip (Statement of Remuneration Paid). Dividends received by Canadian residents from Canadian corporations benefit from the Dividend Tax Credit (DTC), which substantially increases the amount of income you can receive without incurring income tax. See TaxTips.ca - Non-eligible (small business) dividend tax credit (DTC). Quote: For a single individual with no income other than taxable Canadian dividends which are eligible for the small business dividend tax credit, in 2014 approximately $35,551 [...] could be earned before any federal* taxes were payable. * Provincial DTCs vary, and so combined federal/provincial maximums vary. See here. If you're wondering about \"\"non-eligible\"\" vs. \"\"eligible\"\": private small business corporation dividends are generally considered non-eligible for the best DTC benefit—but they get some benefit—while a large public corporation's dividends would generally be considered eligible. Eligible/non-eligible has to do with the corporation's own income tax rates; since Canadian small businesses already get a big tax break that large companies don't enjoy, the DTC for small businesses isn't as good as the DTC for public company dividends. Finally, even if there is hardly any same-year income tax advantage in taking dividends over salary from an active small business corporation (when you factor in both the income tax paid by the corporation and the individual), dividends still allow a business owner to smooth his income over time, which can result in a lower lifetime average tax rate. So you can use your business as a retained earnings piggy bank to spin off dividends that attract less tax than ordinary income. But! ... if you can convince somebody to buy your business from you, then you can benefit from the lifetime capital gains exemption of up to $800,000 on qualifying small business shares. i.e. you can receive up to $800K tax-free on the sale of your small business shares. This lifetime capital gains exemption is a big carrot—designed, I believe, to incentivize Canadian entrepreneurs to develop going-concern businesses that have value beyond their own time in the business. This means building things that would make your business worth buying, e.g. a valued brand or product, a customer base, intellectual property, etc. Of course, there are details and conditions with all of what I described, and I am not an accountant, so please consult a qualified, conflict-free professional if you need advice specific to your situation.\"",
"title": ""
},
{
"docid": "102287",
"text": "\"I'm assuming that by saying \"\"I'm a US resident now\"\" you're referring to the residency determination for tax purposes. Should I file a return in the US even though there is no income here ? Yes. US taxes its residents for tax purposes (which is not the same as residents for immigration or other purposes) on worldwide income. If yes, do I get credits for the taxes I paid in India. What form would I need to submit for the same ? I am assuming this form has to be issued by IT Dept in India or the employer in India ? The IRS doesn't require you to submit your Indian tax return with your US tax return, however they may ask for it later if your US tax return comes under examination. Generally, you claim foreign tax credits using form 1116 attached to your tax return. Specifically for India there may also be some clause in the Indo-US tax treaty that might be relevant to you. Treaty claims are made using form 8833 attached to your tax return, and I suggest having a professional (EA/CPA licensed in your State) prepare such a return. Although no stock transactions were done last year, should I still declare the value of total stocks I own ? If so what is an approx. tax rate or the maximum tax rate. Yes, this is done using form 8938 attached to your tax return and also form 114 (FBAR) filed separately with FinCEN. Pay attention: the forms are very similar with regard to the information you provide on them, but they go to different agencies and have different filing requirements and penalties for non-compliance. As to tax rates - that depends on the types of stocks and how you decide to treat them. Generally, the tax rate for PFIC is very high, so that if any of your stocks are classified as PFIC - you'd better talk to a professional tax adviser (EA/CPA licensed in your State) about how to deal with them. Non-PFIC stocks are dealt with the same as if they were in the US, unless you match certain criteria described in the instructions to form 5471 (then a different set of rules apply, talk to a licensed tax adviser). I will be transferring most of my stock to my father this year, will this need to be declared ? Yes, using form 709. Gift tax may be due. Talk to a licensed tax adviser (EA/CPA licensed in your State). I have an apartment in India this year, will this need to be declared or only when I sell the same later on ? If there's no income from it - then no (assuming you own it directly in your own name, for indirect ownership - yes, you do), but when you sell you will have to declare the sale and pay tax on the gains. Again, treaty may come into play, talk to a tax adviser. Also, be aware of Section 121 exclusion which may make it more beneficial for you to sell earlier.\"",
"title": ""
},
{
"docid": "157712",
"text": "I am a US citizen and I want to transfer some amount 10 lakhs+ to my brother from my NRE account in India to his account. My brother is going to purchase something for his business. He is going to return my amount after 3-4 Months From the description it looks like you would like to loan to your brother on repatriation basis. Yes this is allowed. See the RBI Guide here and here for more details. There are some conditions; (iv) Scheme for raising loans from NRIs on repatriation basis Borrowings not exceeding US$ 2,50,000 or its equivalent in foreign exchange by an individual resident in India from his close relatives resident outside India, subject to the conditions that - a) the loan is free of interest; b) the minimum maturity period of the loan is seven years; c) The amount of loan is received by inward remittance in free foreign exchange through normal banking channels or by debit to the NRE/FCNR account of the non-resident lender; d) The loan is utilised for the borrower's personal purposes or for carrying on his normal business activity but not for carrying on agricultural/plantation activities, purchase of immovable property or shares/debentures/bonds issued by companies in India or for re-lending. Although it is mentioned as Seven years, this is revised to one year. Since he cannot deposit into my NRE account I guess he has to deposit it into my NRO account. A repatriate-able loan as above can be deposited into NRE Account. Is there any illegality here doing such transaction? No. Please ensure proper paper work to show this as loan and document the money trail. Also once I get my money in NRO account do I need to pay taxes in India on the money he deposited? This question does not arise.",
"title": ""
},
{
"docid": "14817",
"text": "\"All the other answers posted thus far discuss matters from the perspective of US tax laws and are unanimous in declaring that what the OP wants to do is indeed a very bad idea. I fully agree: it is a bad idea from the perspective of US tax laws, and is likely a bad idea from the perspective of Indian tax laws too, but what the OP wants to do is (or used to be) common practice in India. In more recent times, India has created a Permanent Account Number (\"\"PAN number\"\") for each taxpayer for income tax purposes, and each bank account or investment must have the owner's (or first-named owner's, in case of a joint account) PAN number associated with it. This most likely has decreased the popularity of such arrangements, or has led to new twists being used. The OP has not indicated the residence and citizenship of his family (or his own status for that matter), but if they are all Indian citizens resident in India and are Hindus, then there might be one mechanism for doing what the OP wants to do: apply for a PAN number in the name of the Hindu Undivided Family and use this number to carry out the investments in the name of the Hindu Undivided Family. (There presumably are similar statuses for undivided families for other religions, but I am not familiar with them). There are lots of matters here which are more legal questions than personal finance questions: e.g. if the OP is a US tax resident, then the family presumably will not be able to claim Hindu Undivided Family status since the OP has been divided from the family for tax purposes (or so I think). Even if HUF status is available, the OP might not be able to act as the pater familias while his father is alive, and so on. Consultation with tax lawyers, not just chartered accountants, in India is certainly advisable.\"",
"title": ""
},
{
"docid": "256395",
"text": "With a question like this you should talk to a tax professional who knows about international tax and knows about both the UK and the country you will be working in. They will give you up to date advice on what can be an extremely complex question. However to get you started I'll tell you what I was told when I did this nearly twenty years ago. It's all about whether you are resident in the UK for tax purposes or not. If you are, you will pay UK tax. If not, you wont (assuming you are being paid outside the UK - check with your professional exactly what is involved). In those days you could be counted as 'non resident' if you spent a complete period of twelve months outside the UK. You can make occasional visits to the UK without invalidating that. Again, check exactly how much you are allowed to return while still being not resident. Usually you will have to pay tax in the country where you are resident, but check the rules there. With some skilful timing you may be able to be considered non-resident in bouth countries, at least for some of the time. Again, your tax professional will know. The bank account question - again get a professional. I don't think it's a problem, but you may have to establish that you are being paid in the foreign country. In general you are going to need an account in the country where you work, so if its a problem get paid there and transfer any money you need in the UK.",
"title": ""
},
{
"docid": "282844",
"text": "If you have non Residency status in Canada you don't need to file Canadian tax return. To confirm your status you need to contact Canada Revenue (send them letter, probably to complete some form).",
"title": ""
},
{
"docid": "75568",
"text": "Here's the real reason OKPay (actually the banks they interface with) won't accept US Citizens. The Foreign Account Tax Compliance Act Congress passed the Foreign Account Tax Compliance Act (FATCA) in 2010 without much fanfare. One reason the act was so quiet was its four-year long ramp up; FATCA did not really take effect until 2014. Never before had a single national government attempted, and so far succeeded in, forcing compliance standards on banks across the world. FATCA requires any non-U.S. bank to report accounts held by American citizens worth over $50,000 or else be subject to 30% withholding penalties and possible exclusion from U.S. markets. By mid-2015, more than 100,000 foreign entities had agreed to share financial information with the IRS. Even Russia and China agreed to FATCA. The only major global economy to fight the Feds is Canada; however it was private citizens, not the Canadian government, who filed suit to block FATCA under the International Governmental Agreement clause making it illegal to turn over private bank account information. Read more: The Tax Implications of Opening a Foreign Bank Account | Investopedia http://www.investopedia.com/articles/personal-finance/102915/tax-implications-opening-foreign-bank-account.asp#ixzz4TzEck9Yo Follow us: Investopedia on Facebook",
"title": ""
},
{
"docid": "239030",
"text": "\"Congrats on the upcoming wedding! Here is the official answer to this question, from the IRS. They note that you can choose to treat your spouse as a US resident for tax purposes and file jointly if you want to, by attaching a certain declaration to your tax return. Though I'm not a tax expert, if your partner has significant income it seems like this might increase your taxes due. You can also apply for an SSN (used for tax filings, joint or separate return) at a social security office or US consulate, by form SS-5, or file form W-7 with the IRS to get a Taxpayer Identification Number which is just as useful for this purpose. Without that, you can write \"\"Non Resident Alien\"\" (or \"\"NRA\"\") in the box for your partner's SSN, and mail in a paper return like that. See IRS Publication 17 page 22 (discussions on TurboTax here, here, etc.).\"",
"title": ""
}
] |
PLAIN-564
|
angiogenesis
|
[
{
"docid": "MED-4089",
"text": "Studies have shown an inverse relationship between the consumption of apples and the risk of several cancers. The peels of apple, which have been shown to possess exceptionally high concentrations of antioxidants, are often discarded. In this study, we evaluated the antiproliferative effects of apple peel extract (APE) in variety of cancer cell types. Our data demonstrated that APE, obtained from organic Gala apples, imparted significant reduction in the viability of a variety of cancer cell lines. Further, our data showed a significant decrease in growth and clonogenic survival of human prostate carcinoma CWR22Rnu1 and DU145 cells and breast carcinoma Mcf-7 and Mcf-7:Her18 cells. Also, the antiproliferative effects of APE were found to be accompanied by a G0-G1 phase arrest of prostate and breast cancer cells. Furthermore, APE treatment resulted in a marked concentration-dependent decrease in the protein levels of proliferative cell nuclear antigen, a marker for proliferation. In addition, APE treatment resulted in a marked increase in maspin, a tumor suppressor protein that negatively regulates cell invasion, metastasis, and angiogenesis. Our data suggested that APE possesses strong antiproliferative effects against cancer cells, and apple peels should not be discarded from the diet. Detailed mechanistic studies, especially in appropriate in vivo animal models, are needed to further examine the antiproliferative and preventive effects of APE against cancer.",
"title": "Antiproliferative effects of apple peel extract against cancer cells."
},
{
"docid": "MED-2572",
"text": "In traditional cultures, balancing health with a balanced lifestyle was a core belief. The diseases of modern civilization were rare. Indigenous people have patterns of illness very different from Western civilization; yet, they rapidly develop diseases once exposed to Western foods and lifestyles. Food and medicine were interwoven. All cultures used special or functional foods to prevent disease. Food could be used at different times either as food or medicine. Foods, cultivation, and cooking methods maximized community health and well-being. With methods passed down through generations, cooking processes were utilized that enhanced mineral and nutrient bioavailability. This article focuses on what researchers observed about the food traditions of indigenous people, their disease patterns, the use of specific foods, and the environmental factors that affect people who still eat traditional foods.",
"title": "Traditional non-Western diets."
},
{
"docid": "MED-3549",
"text": "Studies have shown that fisetin, a small phytochemical molecule, has antitumor activity; however, its antiangiogenic activity has not yet been examined. Accordingly, herein, we investigated the antiangiogenic efficacy and associated mechanisms of fisetin in human umbilical vein endothelial cells (HUVECs). Fisetin (10-50 μM) strongly inhibited the regular serum plus growth supplement- and vascular endothelial growth factor (VEGF)-induced growth (up to 92%, P < 0.001) and survival (up to 16%, P < 0.001) of HUVEC in a dose- and time-dependent manner. Fisetin also caused cell cycle arrest at G(1) (strong) and G(2)/M (moderate) phases together with a decrease in cyclin D1 and an increase in p53 levels. Fisetin-caused cell death was accompanied by decreased expression of survivin and an increase in cleaved levels of caspases-3 and -7 and poly-(ADP-ribose) polymerase along with an increased ratio of Bax to Bcl-2. Furthermore, fisetin inhibited capillary-like tube formation on Matrigel (up to 85%, P < 0.001) as well as migration (up to 66%, P < 0.001), which were associated with decreased expression of endothelial nitric oxide synthase (eNOS) and VEGF in HUVEC. It also decreased the expression of eNOS, VEGF, inducible nitric oxide synthase, matrix metalloproteinase-2 and -9 in A549 and DU145 human cancer cells. In vivo matrigel plug assay in mice showed significant decrease in size (up to 43%, P < 0.001), vascularization and hemoglobin content (up to 94%, P < 0.001) in the plugs from fisetin-treated, compared with control mice. Overall, these results suggest that fisetin inhibits various attributes of angiogenesis, which might contribute to its reported antitumor effects, and therefore, fisetin warrants further investigation for its angiopreventive potential toward cancer control.",
"title": "Fisetin inhibits various attributes of angiogenesis in vitro and in vivo--implications for angioprevention."
},
{
"docid": "MED-2580",
"text": "Adequate fruit and vegetable intake was suggested to protect against colorectal cancer and colorectal adenomas; however, several recent prospective studies reported no association. We examined the association between fruits and vegetables and adenomatous polyp recurrence in the Polyp Prevention Trial (PPT). The PPT was a low-fat, high-fiber, high-fruit, and vegetable dietary intervention trial of adenoma recurrence, in which there were no differences in the rate of adenoma recurrence in participants in the intervention and control arms of the trial. In this analysis of the entire PPT trial–based cohort, multiple logistic regression analysis was used to estimate the odds ratio (OR) of advanced and nonadvanced adenoma recurrence within quartiles of baseline and change (baseline minus the mean over 3 y) in fruit and vegetable intake, after adjustment for age, total energyy intake, use of nonsteroidal anti-inflammatory drugs, BMI, and gender. There were no significant associations between nonadvanced adenoma recurrence and overall change in fruit and vegetable consumption; however, those in the highest quartile of change in dry bean intake (greatest increase) compared with those in the lowest had a significantly reduced OR for advanced adenoma recurrence (OR = 0.35; 95% CI, 0.18–0.69; P for trend = 0.001). The median in the highest quartile of change in dry bean intake was 370% higher than the baseline intake. The PPT trial–based cohort provides evidence that dry beans may be inversely associated with advanced adenoma recurrence.",
"title": "High Dry Bean Intake and Reduced Risk of Advanced Colorectal Adenoma Recurrence among Participants in the Polyp Prevention Trial"
},
{
"docid": "MED-3555",
"text": "A number of epidemiological studies have investigated associations between various phytochemicals and cancer risk. Phytoestrogens and carotenoids are the two most commonly studied classes of phytochemicals; phytosterols, isothiocyanates, and chlorophyll also have been investigated, although to a much lesser extent. Because there have been no systematic reviews of the literature on all phytochemicals and cancer risk to date, this article systematically reviews 96 published epidemiological studies that examined associations between phytochemicals and cancer risk. Most studies found null associations between individual phytochemicals and cancer risk at various sites. In addition, results from past studies have been largely inconsistent, and observed associations have been of relatively modest magnitude. The most consistent protective effects were observed for higher levels--dietary intake, serum, plasma, or urinary metabolites--of β-carotene and renal cell cancer, β-cryptoxanthin and lung cancer, isothiocyanates and lung cancer, isothiocyanates and gastrointestinal cancer, lignans and postmenopausal breast cancer, and flavonoids and lung cancer. Although elevated risk of certain cancers with higher levels of certain phytochemicals was observed, an insufficient pool of studies examining the same associations or inconsistent findings across studies limit the ability to conclude that any one phytochemical increases cancer risk. Additional research is needed to support previously identified associations in cases where only one study has examined a particular relationship. Importantly, continued research efforts are needed to evaluate the cumulative and interactive effects of numerous phytochemicals and phytochemical-rich foods on cancer risk.",
"title": "Phytochemicals and cancer risk: a review of the epidemiological evidence."
},
{
"docid": "MED-2577",
"text": "A case-control study probing the role of diet on the incidence of colorectal cancer was undertaken in Athens, Greece, in a population characterized by ethnic homogeneity but substantial heterogeneity with respect to dietary habits. The case series consisted of 100 consecutive patients with histologically confirmed colorectal cancer admitted to two large hospitals of Athens during a 16-month period; the control series consisted of orthopaedic patients, admitted to the same hospitals during the same time period, individually matched to the index cases by age and sex. Dietary histories concerning the frequency of consumption (per month or per week) of about 80 food items were obtained by the same interviewer. Cases reported significantly less frequent consumption of vegetables (particularly beets, spinach, lettuce and cabbage) and, independently, significantly more frequent consumption of meat (notably lamb and beef). Between the two extremes (high-vegetable, low-meat diet versus high-meat, low-vegetable diet) a risk ratio of about 8 appears to exist, sufficient (in size and direction) to explain a substantial part of the international variation in the incidence of colorectal cancer. Significant associations were not found with beer or other alcoholic beverages, and significant interactions were not noted with respect to age, sex and anatomic localization (colon vs. rectum).",
"title": "Diet and colorectal cancer: a case-control study in Greece."
},
{
"docid": "MED-2579",
"text": "There are now extensive scientific data suggesting the potential role of dietary and non-dietary phytochemicals in the prevention and control of prostate cancer (PCA) growth and progression. PCA is a disease of elderly male populations with a relatively slower rate of growth and progression as compared to most other cancers and, therefore, is a candidate disease for preventive intervention. Overall, PCA growth and progression involve aberrant mitogenic and survival signaling and deregulated cell cycle progression, accompanied by gradual accumulation of genetic and epigenetic changes over a period of years. Several mechanisms, including overexpression of growth, survival and angiogenic factors and their receptors, together with a loss/decrease of tumor suppressor p53, retinoblastoma and cyclin-dependent kinase inhibitor, have been implicated in PCA growth and progression. Therefore, phytochemicals targeting these molecular events could have a promising role in PCA prevention and/or therapy. Inositol hexaphosphate (IP6) is a major constituent of most cereals, legumes, nuts, oil seeds and soybean. Taken orally as an over-the-counter dietary/nutrient supplement, and is recognised as offering several health benefits without any known toxicity. In vitro anticancer efficacy of IP6 has been observed in many human, mouse and rat prostate cancer cells. Completed studies also show that oral feeding of IP6 inhibits human PCA xenograft growth in nude mice without toxicity. In a recently completed pilot study, we observed similar preventive effects of IP6 on prostate tumorigenesis in the TRAMP model. Mechanistic studies indicate that IP6 targets mitogenic and survival signaling, as well as cell cycle progression, in PCA cells. IP6 is also shown to target molecular events associated with angiogenesis. Moreover, IP6 has pleiotropic molecular targets for its overall efficacy against PCA and, therefore, could be a suitable candidate agent for preventive intervention of this malignancy in humans.",
"title": "Prostate cancer and inositol hexaphosphate: efficacy and mechanisms."
},
{
"docid": "MED-2571",
"text": "Background Prospective, randomized, pilot clinical study was conducted to evaluate the beneficial effects of inositol hexaphosphate (IP6) + Inositol in breast cancer patients treated with adjuvant therapy. Patients and methods Patients with invasive ductal breast cancer where polychemotherapy was indicated were monitored in the period from 2005-2007. Fourteen patients in the same stage of ductal invasive breast cancer were involved in the study, divided in two randomized groups. One group was subjected to take IP6 + Inositol while the other group was taking placebo. In both groups of patients the same laboratory parameters were monitored. When the treatment was finished, all patients have filled questionnaires QLQ C30 and QLQ-BR23 to determine the quality of life. Results Patients receiving chemotherapy, along with IP6 + Inositol did not have cytopenia, drop in leukocyte and platelet counts. Red blood cell counts and tumor markers were unaltered in both groups. However, patients who took IP6 + Inositol had significantly better quality of life (p = 0.05) and functional status (p = 0.0003) and were able to perform their daily activities. Conclusion IP6 + Inositol as an adjunctive therapy is valuable help in ameliorating the side effects and preserving quality of life among the patients treated with chemotherapy.",
"title": "Efficacy of IP6 + inositol in the treatment of breast cancer patients receiving chemotherapy: prospective, randomized, pilot clinical study"
},
{
"docid": "MED-3552",
"text": "The study evaluated the protective effects of purple rice (Oryza sativa L.) bran extract (PRE) and its constituents, cyanidin and peonidin, against angiogenesis induced by vascular endothelial growth factor (VEGF). The effects of VEGF and PRE were examined by in vitro tube formation assays and following 14-day co-culture of human umbilical vein endothelial cells (HUVECs) and fibroblasts. The antiangiogenic mechanism of PRE was evaluated by VEGF-induced proliferation and migration of HUVECs and/or human retinal microvascular endothelial cells (HRMECs) and phosphorylation of extracellular signal-regulated kinase (ERK) and p38. The PRE significantly suppressed VEGF-induced tube formation, proliferation and migration in HUVECs and HRMECs as well as phosphorylation of ERK and p38. Cyanidin and peonidin also suppressed the proliferation and migration induced by VEGF. These findings indicate that PRE and anthocyanidins suppress VEGF-induced angiogenesis by inhibiting proliferation and migration and suggest that the inhibition of phosphorylated-ERK and -p38 may be involved in the underlying mechanism. Copyright © 2011 John Wiley & Sons, Ltd.",
"title": "Purple rice (Oryza sativa L.) extract and its constituents inhibit VEGF-induced angiogenesis."
},
{
"docid": "MED-2570",
"text": "The functional properties, including antioxidant and chemopreventative capacities as well as the inhibitory effects on angiotensin-converting enzyme (ACE), α-glucosidase and pancreatic lipase, of three Australian-grown faba bean genotypes (Nura, Rossa and TF(Ic*As)*483/13) were investigated using an array of in vitro assays. Chromatograms of on-line post column derivatisation assay coupled with HPLC revealed the existence of active phenolics (hump) in the coloured genotypes, which was lacking in the white-coloured breeding line, TF(Ic*As)*483/13. Roasting reduced the phenolic content, and diminished antioxidant activity by 10-40 % as measured by the reagent-based assays (diphenylpicrylhydrazyl, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) and oxygen radical absorbance capacity) in all genotypes. Cell culture-based antioxidant activity assay (cellular antioxidant activity) showed an increase of activity in the coloured genotypes after roasting. Faba bean extracts demonstrated cellular protection ability against H₂O₂-induced DNA damage (assessed using RAW264.7 cells), and inhibited the proliferation of all human cancer cell lines (BL13, AGS, Hep G2 and HT-29) evaluated. However, the effect of faba bean extracts on the non-transformed human cells (CCD-18Co) was negligible. Flow cytometric analyses showed that faba bean extracts successfully induced apoptosis of HL-60 (acute promyelocytic leukaemia) cells. The faba bean extracts also exhibited ACE, α-glucosidase and pancreatic lipase inhibitory activities. Overall, extracts from Nura (buff-coloured) and Rossa (red-coloured) were comparable, while TF(Ic*As)*483/13 (white-coloured) contained the lowest phenolic content and exhibited the least antioxidant and enzyme inhibition activities. These results are important to promote the utilisation of faba beans in human diets for various health benefits.",
"title": "In vitro investigations of the potential health benefits of Australian-grown faba beans (Vicia faba L.): chemopreventative capacity and inhibitory ..."
},
{
"docid": "MED-4090",
"text": "Apple peel is a waste product from dried apple manufacture. The content of phenolic compounds, dietary fiber, and mineral are higher in apple peel, compared to other edible parts of this fruits. The objective of this study was to develop an ingredient from Granny Smith apple peel, using a pilot scale double drum-dryer, as drying technology. The control of all steps to maximize the retention of phenolic compounds and dietary fiber was considered. Operational conditions, such as drying temperature and time were determined, as well as important preprocessing steps like grinding and PPO inhibition. In addition, the physical-chemical characteristics, mineral and sugar content, and technological functional properties such as water retention capacity, solubility index, and dispersability among others, were analyzed. A simple, economical, and suitable pilot scale process, to produce a powder ingredient from apple peel by-product, was obtained. The drying process includes the application of ascorbic acid at 0.5% in the fresh apple peel slurry, drum-dryer operational conditions were 110 degrees C, 0.15 rpm and 0.2 mm drum clearance. The ingredient developed could be considered as a source of phenolic compounds (38.6 mg gallic acid equivalent/g dry base) and dietary fiber (39.7% dry base) in the formulation of foods. Practical Application: A method to develop an ingredient from Granny Smith apple peel using a pilot scale double drum-dryer as drying technology was developed. The method is simple, economical, feasible, and suitable and maximizes the retention of phenolic compounds and dietary fiber present in the raw matter. The ingredient could be used in the formulation of foods.",
"title": "Development of an ingredient containing apple peel, as a source of polyphenols and dietary fiber."
},
{
"docid": "MED-3548",
"text": "Cancer metastasis refers to the spread of cancer cells from the primary neoplasm to distant sites, where secondary tumors are formed, and is the major cause of death from cancer. Natural phytochemicals containing phenolic compounds have been widely demonstrated to have the capability to prevent cancer metastasis. Among phenolic compounds, flavonoids are a very large subclass, and they are abundant in food and nutraceuticals. The number of reports demonstrating that flavonoids are an effective natural inhibitor of cancer invasion and metastasis is increasing in the scientific literature. Catechin derivatives, (−)-epigallocatechin-3-gallate, (−)-epigallocatechin, (−)-epicatechin-3-gallate,and (−)-epicatechin, are the most studied compounds in this topic so far; genistein/genistin, silibinin, quercetin, and anthocyanin have also been widely investigated for their inhibitory activities on invasion/metastasis. Other flavonoids in dietary vegetable foods that are responsible for anti-invasive and anti-metastatic activities of tumors include luteolin,apigenin, myricetin, tangeretin, kaempferol, glycitein, licoricidin,daidzein, and naringenin. To effectively overcome the metastatic cascade, including cell-cell attachment, tissue barrier degradation, migration, invasion, cell-matrix adhesion,and angiogenesis, it is essential that a bioactive compound prevent tumor cells from metastasizing. This review summarizes the effects of flavonoids on the metastatic cascade and the related proteins, the in vitro anti-invasive activity of flavonoids against cancer cells, and the effects of flavonoids on antiangiogenic and in vivo anti-metastatic models. The available scientific evidence indicates that flavonoids are a ubiquitous dietary phenolics subclass and exert extensive in vitro anti-invasive and in vivo anti-metastatic activities.",
"title": "Flavonoids, a ubiquitous dietary phenolic subclass, exert extensive in vitro anti-invasive and in vivo anti-metastatic activities."
},
{
"docid": "MED-2574",
"text": "Inositol hexaphosphate (IP(6)) is a naturally occurring polyphosphorylated carbohydrate, abundantly present in many plant sources and in certain high-fiber diets, such as cereals and legumes. In addition to being found in plants, IP(6) is contained in almost all mammalian cells, although in much smaller amounts, where it is important in regulating vital cellular functions such as signal transduction, cell proliferation, and differentiation. For a long time IP(6) has been recognized as a natural antioxidant. Recently IP(6) has received much attention for its role in cancer prevention and control of experimental tumor growth, progression, and metastasis. In addition, IP(6) possesses other significant benefits for human health, such as the ability to enhance immune system, prevent pathological calcification and kidney stone formation, lower elevated serum cholesterol, and reduce pathological platelet activity. In this review we show the efficacy and discuss some of the molecular mechanisms that govern the action of this dietary agent. Exogenously administered IP(6) is rapidly taken up into cells and dephosphorylated to lower inositol phosphates, which further affect signal transduction pathways resulting in cell cycle arrest. A striking anticancer action of IP(6) was demonstrated in different experimental models. In addition to reducing cell proliferation, IP(6) also induces differentiation of malignant cells. Enhanced immunity and antioxidant properties also contribute to tumor cell destruction. Preliminary studies in humans show that IP(6) and inositol, the precursor molecule of IP(6), appear to enhance the anticancer effect of conventional chemotherapy, control cancer metastases, and improve quality of life. Because it is abundantly present in regular diet, efficiently absorbed from the gastrointestinal tract, and safe, IP(6) + inositol holds great promise in our strategies for cancer prevention and therapy. There is clearly enough evidence to justify the initiation of full-scale clinical trials in humans.",
"title": "Protection against cancer by dietary IP6 and inositol."
},
{
"docid": "MED-3553",
"text": "Several epidemiological studies have indicated that abundant consumption of foods from plant origin is associated with a reduced risk of developing several types of cancers. This chemopreventive effect is related to the high content of these foods in phytochemicals, such as polyphenols, that interfere with several processes involved in cancer progression including tumor cell growth, survival and angiogenesis. In addition to the low intake of plant-based foods, increased body mass and physical inactivity have recently emerged as other important lifestyle factors influencing cancer risk, leading to the generation of low-grade chronic inflammatory conditions which are a key process involved in tumor progression. The objectives of the current study are to investigate the inhibitory effects of these polyphenols on angiogenesis triggered by an inflammatory cytokine (IL-6) and to determine the mechanisms underlying this action. We found that, among the tested polyphenols, apigenin and luteolin were the most potent angiogenesis inhibitors through their inhibitory effect on the inflammatory cytokine IL-6/STAT3 pathway. These effects resulted in modulation of the activation of extracellular signal-regulated kinase-1/2 signaling triggered by IL-6, as well as in a marked reduction in the proliferation, migration and morphogenic differentiation of endothelial cells. Interestingly, these polyphenols also modulated the expression of IL-6 signal transducing receptor (IL-6Rα) and the secretion of the extracellular matrix degrading enzyme MMP-2 as well as the expression of suppressor of cytokine signaling (SOCS3) protein. Overall, these results may provide important new information on the role of diet in cancer prevention. Copyright © 2012 Elsevier Inc. All rights reserved.",
"title": "Diet-derived polyphenols inhibit angiogenesis by modulating the interleukin-6/STAT3 pathway."
},
{
"docid": "MED-2583",
"text": "Inositol hexaphosphate (IP(6)), a naturally polyphosphorylated carbohydrate, has been reported to have significant in vivo and in vitro anticancer activity against numerous tumours, such as colon, prostate, breast, liver and rhabdomyosarcomas. To confirm this activity in haematological malignancies and to characterize some of the mechanisms of IP(6) action, we analysed its effects on human leukaemic cell lines and fresh chronic myelogenous leukaemia (CML) progenitor cells using a combined cellular and molecular approach. IP(6) had a dose-dependent cytotoxic effect on all of the evaluated cell lines, with accumulation in the G2M phase in two out of five cell lines tested. At the molecular level, cDNA microarray analysis after IP(6) exposure showed an extensive downmodulation of genes involved in transcription and cell cycle regulation and a coherent upregulation of cell cycle inhibitors. Furthermore, IP(6) treatment of fresh leukaemic samples of bone marrow CD34+ CML progenitor cells significantly inhibited granulocyte-macrophage colony-forming unit (CFU-GM) formation (P = 0.0062) in comparison to normal bone marrow specimens, which were not affected. No differentiating effect on HL60 cells was observed. Taken together, our results confirm the antiproliferative activity of IP(6) and suggest that it may have a specific antitumour effect also in chronic myeloid leukaemias, via active gene modulation.",
"title": "Effect of inositol hexaphosphate (IP(6)) on human normal and leukaemic haematopoietic cells."
},
{
"docid": "MED-2584",
"text": "In a 6-year prospective study, the authors examined the relation between diet and incident colon cancer among 32,051 non-Hispanic white cohort members of the Adventist Health Study (California, 1976-1982) who, at baseline, had no documented or reported history of cancer. The risk of colon cancer was determined from proportional hazards regression with adjustment for age and other covariates. The authors found a positive association with total meat intake (risk ratio (RR) for > or =1 time/week vs. no meat intake = 1.85, 95% confidence interval (CI) 1.19-2.87; p for trend = 0.01) and, among subjects who favored specific types of meat, positive associations with red meat intake (RR for > or =1 time/week vs. no red meat intake = 1.90, 95% CI 1.16-3.11; p for trend = 0.02) and white meat intake (RR for > or =1 time/week vs. no white meat intake = 3.29, 95% CI 1.60-6.75; p for trend = 0.006). An inverse association with legume intake (RR for >2 times/week vs. <1 time/week = 0.53, 95% CI 0.33-0.86; p for trend = 0.03) was observed. Among men, a positive association with body mass index was observed (relative to the RR for tertile III (>25.6 kg/m2) vs. tertile I (<22.5 kg/m2) = 2.63, 95% CI 1.12-6.13; p for trend = 0.05). A complex relation was identified whereby subjects exhibiting a high red meat intake, a low legume intake, and a high body mass experienced a more than threefold elevation in risk relative to all other patterns based on these variables. This pattern of putative risk factors would likely contribute to increases in both insulin resistance (high body mass, high red meat intake) and glycemic load (low legume intake), a synergism that, if causal, implicates hyperinsulinemic exposure in colon carcinogenesis. The overall findings from this cohort identify both red meat intake and white meat intake as important dietary risk factors for colon cancer and raise the possibility that the risk due to red meat intake reflects a more complex etiology.",
"title": "Dietary risk factors for colon cancer in a low-risk population."
},
{
"docid": "MED-4465",
"text": "Adult stem cells of the mammary gland (MaSCs) are a highly dynamic population of cells that are responsible for the generation of the gland during puberty and its expansion during pregnancy. In recent years significant advances have been made in understanding how these cells are regulated during these developmentally important processes both in humans and in mice. Understanding how MaSCs are regulated is becoming a particularly important area of research, given that they may be particularly susceptible targets for transformation in breast cancer. Here, we summarize the identification of MaSCs, how they are regulated and the evidence for their serving as the origins of breast cancer. In particular, we focus on how changes in MaSC populations may explain both the increased risk of developing aggressive ER/PR(−) breast cancer shortly after pregnancy and the long-term decreased risk of developing ER/PR(+) tumors.",
"title": "From milk to malignancy: the role of mammary stem cells in development, pregnancy and breast cancer"
},
{
"docid": "MED-4464",
"text": "Over the last decade, the notion that tumors are maintained by their own stem cells, the so-called cancer stem cells, has created great excitement in the research community. This review attempts to summarize the underlying concepts of this notion, to distinguish hard facts from beliefs and to define the future challenges of the field.",
"title": "The cancer stem cell: premises, promises and challenges."
},
{
"docid": "MED-2559",
"text": "Inositol hexaphosphate (IP6) has anti-cancer properties, but recently other extracellular functions have been observed for IP6, including enhancing superoxide production and phagocytosis by neutrophils in the presence of microbial stimuli. This study investigated other inflammatory functions of IP6 on adherent neutrophils. The effect of IP6 on the release of IL-8, tumour necrosis factor (TNF-alpha) and IL-6 by neutrophils attached to either plastic or laminin for up to 6 hours in response to stimulation with lipopolysaccharide or N-formyl-Met-Leu-Phe (fMLP) was investigated. An increase in IL-8 secretion by stimulated cells occurred in the presence of IP6. The incubation of cells attached to laminin with IP6 alone (100-250 BM) did not effect cell morphology, but in the presence of 10(-7) M fMLP altered cell shape. A direct effect of IP6 on cell function was to trigger a sustained assembly of F-actin. Thus, exposure of neutrophils to low levels of IP6 appears to modulate selective neutrophil functions.",
"title": "Effect of IP6 on human neutrophil cytokine production and cell morphology."
},
{
"docid": "MED-3554",
"text": "A great deal of effort is now being devoted to the development of new drugs that hopefully will control the spread of inoperable cancer by safely inhibiting tumor-evoked angiogenesis. However, there is growing evidence that certain practical nutritional measures have the potential to slow tumor angiogenesis, and it is reasonable to anticipate that, by combining several measures that work in distinct but complementary ways to impede the angiogenic process, a clinically useful 'multifocal angiostatic therapy' (MAT) might be devised. Several measures which might reasonably be included in such a protocol are discussed below, and include: a low-fat, low-glycemic index vegan diet, which may down-regulate the systemic IGF-I activity that supports angiogenesis; supplemental omega-3-rich fish oil, which has been shown to inhibit endothelial expression of Flk-1, a functionally crucial receptor for VEGF, and also can suppress tumor production of pro-angiogenic eicosanoids; high-dose selenium, which has recently been shown to inhibit tumor production of VEGF; green tea polyphenols, which can suppress endothelial responsiveness to both VEGF and fibroblast growth factor; and high-dose glycine, whose recently reported angiostatic activity may reflect inhibition of endothelial cell mitosis, possibly mediated by activation of glycine-gated chloride channels. In light of evidence that tumor-evoked angiogenesis has a high requirement for copper, copper depletion may have exceptional potential as an angiostatic measure, and is most efficiently achieved with the copper-chelating drug tetrathiomolybdate. If logistical difficulties make it difficult to acquire this experimental drug, high-dose zinc supplementation can achieve a slower depletion of the body's copper pool, and in any case can be used as maintenance therapy to maintain an adequate level of copper depletion. A provisional protocol is offered for a nutritionally based MAT entailing a vegan diet and supplemental intakes of fish oil, selenium, green tea polyphenols, glycine, and zinc. Inasmuch as cox-2 is overexpressed in many cancers, and cAMP can boost tumor production of various angiogenic factors as well as autogenous growth factors, adjunctive use of cox-2-specific NSAIDS may be warranted in some cases.",
"title": "A wholly nutritional 'multifocal angiostatic therapy' for control of disseminated cancer."
},
{
"docid": "MED-4319",
"text": "The article gives an overview of phytic acid in food and of its significance for human nutrition. It summarises phytate sources in foods and discusses problems of phytic acid/phytate contents of food tables. Data on phytic acid intake are evaluated and daily phytic acid intake depending on food habits is assessed. Degradation of phytate during gastro-intestinal passage is summarised, the mechanism of phytate interacting with minerals and trace elements in the gastro-intestinal chyme described and the pathway of inositol phosphate hydrolysis in the gut presented. The present knowledge of phytate absorption is summarised and discussed. Effects of phytate on mineral and trace element bioavailability are reported and phytate degradation during processing and storage is described. Beneficial activities of dietary phytate such as its effects on calcification and kidney stone formation and on lowering blood glucose and lipids are reported. The antioxidative property of phytic acid and its potentional anticancerogenic activities are briefly surveyed. Development of the analysis of phytic acid and other inositol phosphates is described, problems of inositol phosphate determination and detection discussed and the need for standardisation of phytic acid analysis in foods argued.",
"title": "Phytate in foods and significance for humans: food sources, intake, processing, bioavailability, protective role and analysis."
},
{
"docid": "MED-2568",
"text": "Inositol hexaphosphate (InsP6 or IP6) is ubiquitous. At 10 microM to 1 mM concentrations, IP6 and its lower phosphorylated forms (IP(1-5)) as well as inositol (Ins) are contained in most mammalian cells, wherein they are important in regulating vital cellular functions such as signal transduction, cell proliferation and differentiation. A striking anti-cancer action of IP6 has been demonstrated both in vivo and in vitro, which is based on the hypotheses that exogenously administered IP6 may be internalized, dephosphorylated to IP(1-5), and inhibit cell growth. There is additional evidence that Ins alone may further enhance the anti-cancer effect of IP6. Besides decreasing cellular proliferation, IP6 also causes differentiation of malignant cells often resulting in a reversion to normal phenotype. These data strongly point towards the involvement of signal transduction pathways, cell cycle regulatory genes, differentiation genes, oncogenes and perhaps, tumor suppressor genes in bringing about the observed anti-neoplastic action of IP6.",
"title": "IP6: a novel anti-cancer agent."
},
{
"docid": "MED-2573",
"text": "A significant anticancer activity of the naturally occurring carbohydrate inositol hexaphosphate (IP(6)) has been reported against numerous cancer models. Since tumors require angiogenesis for growth and metastasis, we hypothesize that IP(6) reduces tumor growth by inhibiting angiogenesis. Because angiogenesis depends on the interaction between endothelial and tumor cells, we investigated the effect of IP(6) on both. IP(6) inhibited the proliferation and induced the differentiation of endothelial cells in vitro; the growth of bovine aortic endothelial cells (BAECs) evaluated by MTT proliferation assay was inhibited in a dose-dependent manner (IC(50) = 0.74 mM). The combination of IP(6) and vasostatin, a calreticulin fragment with anti-angiogenic activity, was synergistically superior in growth inhibition than either compound. IP(6) inhibited human umbilical vein endothelial cell (HUVEC) tube formation (in vitro capillary differentiation) on a reconstituted extracellular matrix, Matrigel, and disrupted pre-formed tubes. IP(6) significantly reduced basic fibroblast growth factor (bFGF)-induced vessel formation (P < 0.01) in vivo in Matrigel plug assay. Exposure of HepG2, a human hepatoma cell line, to IP(6) for 8 h, resulted in a dose-dependent decrease in the mRNA levels of vascular endothelial growth factor (VEGF), as assessed by RT-PCR. IP(6) treatment of HepG2 cells for 24 h also significantly reduced the VEGF protein levels in conditioned medium, in a concentration-dependent manner (P = 0.012). Thus, IP(6) has an inhibitory effect on induced angiogenesis.",
"title": "Anti-angiogenic activity of inositol hexaphosphate (IP6)."
},
{
"docid": "MED-3550",
"text": "Between 2000 and 2050, the number of new cancer patients diagnosed annually is expected to double, with an accompanying increase in treatment costs of more than $80 billion over just the next decade. Efficacious strategies for cancer prevention will therefore be vital for improving patients' quality of life and reducing healthcare costs. Judah Folkman first proposed antiangiogenesis as a strategy for preventing dormant microtumors from progressing to invasive cancer. Although antiangiogenic drugs are now available for many advanced malignancies (colorectal, lung, breast, kidney, liver, brain, thyroid, neuroendocrine, multiple myeloma, myelodysplastic syndrome), cost and toxicity considerations preclude their broad use for cancer prevention. Potent antiangiogenic molecules have now been identified in dietary sources, suggesting that a rationally designed antiangiogenic diet could provide a safe, widely available, and novel strategy for preventing cancer. This paper presents the scientific, epidemiologic, and clinical evidence supporting the role of an antiangiogenic diet for cancer prevention.",
"title": "Tumor Angiogenesis as a Target for Dietary Cancer Prevention"
},
{
"docid": "MED-2575",
"text": "Introduction Matrix metalloproteinases (MMPs) have repeatedly been shown to play a very active role in extracellular matrix degradation associated with tumor invasion and metastasis. Tissue inhibitors of MMPs (TIMPs) are well-known for their ability to inhibit MMP activity thereby inhibiting malignant progression. Inositol hexaphosphate (IP6 phytic acid) has been recognized to have both preventive and therapeutic effects against various cancers including that of colon. In in vitro studies, IP6 has been demonstrated to inhibit cancer cell adhesion and migration. In the present study, the effect of IP6 on the expression of MMP and TIMP genes was evaluated in unstimulated and IL-1β-stimulated colon cancer cell line Caco-2. Materials and methods Real-time QRT-PCR was used to validate the transcription level of selected MMP and TIMP genes in Caco-2 cells after treatment with 1 ng/ml of IL-1β, 2.5 mM of IP6, and both for 6, 12, and 24 h. Results Stimulation of cells with IL-1β only resulted in an overexpression of MMP and their TIMP mRNAs. A significant decrease in MMP-13, MMP-3, MMP-2, and TIMP-1 basal expression was achieved by IP6. IP6 was also an efficient downregulator of MMP-1, MMP-9, and TIMP-2 genes transcription stimulated by IL-1β in 6 h lasting culture. After 12 h, IL-1β-induced MMP-2 mRNA expression was significantly reduced by IP6. Conclusion Proinflammatory cytokine IL-1β upregulates MMP and TIMP mRNAs expression in colon cancer epithelial cells Caco-2. IP6 (2.5 mM) influences constitutive expression of both MMP and TIMP genes and downregulates IL-1β stimulated transcription of some of these genes. IP6 exerts its anti-metastatic activity through modulation of MMP and TIMP genes expression to prevent cancer cell migration and invasion.",
"title": "The effect of inositol hexaphosphate on the expression of selected metalloproteinases and their tissue inhibitors in IL-1β-stimulated colon cancer cells"
},
{
"docid": "MED-2581",
"text": "A hospital-based case-control study of diet and colorectal cancer was conducted among Chinese in Singapore (who constitute 77% of the population). A total of 203 cases and 425 controls were included. A history of the usual dietary intake one year prior to interview was taken using a quantitative food frequency questionnaire. Daily intakes of nutrients and selected food items were computed and stratified by tertiles of the control range, to assess risk in low-, medium- and high-intake categories. Effects were adjusted in analysis for age, sex, Chinese dialect group and occupation. For cancers of colon and rectum combined, significant observations were a protective effect of high cruciferous vegetable intake (OR = 0.50, p less than 0.01) and a predisposing effect of a high meat/vegetable consumption ratio (OR = 1.77, p less than 0.05). Similar results were observed for colon cancer alone. For rectal cancer alone (only 71 cases), significant (p less than 0.05) protective effects were observed for high intakes of protein (OR = 0.61), fibre (OR = 0.46), beta-carotene (OR = 0.54), cruciferous vegetables (OR = 0.51) and total vegetables (OR = 0.51). When further assessed by multiple logistic regression, tests for trend and assessment of risk in the extreme highest and lowest quintiles of the control range, the factors consistently significant were cruciferous vegetable intake and the meat/vegetable ratio. A particularly high relative risk was also noted in association with low coffee consumption (OR = 1.59, with p less than 0.05 for trend). No consistent trends were noted for fat or fibre intakes. For non-dietary variables investigated, a history of cholecystectomy increased the risk of both cancers combined (OR = 3.43, p less than 0.05) and colon cancer alone (OR = 4.39, p less than 0.01). This study in an Asian population of countries of Southern and Eastern Asia newly undergoing industrialization and in which rapid economic change is reflected in changing cancer patterns, suggests that the protective effects of certain dietary constituents, notably the cruciferous vegetables, may be more important than the hitherto stressed carcinogenic potential of fat and protein.",
"title": "Colorectal cancer and diet in an Asian population--a case-control study among Singapore Chinese."
},
{
"docid": "MED-3551",
"text": "Breast cancer is the leading cause of cancer-related deaths for women in the United States and the rest of the world. About 8% of women develop breast cancer during the course of their lives. Dietary habits are closely associated with both the risk and progression of breast cancer. Dietary agents have accumulated increasing importance with regards to the prevention and treatment of breast cancer. One such manner by which these compounds can target breast cancer development and progression is through interference with the angiogenic pathways. Angiogenesis is an intricate process that involves the development of new capillaries from previously existing blood vessels. Disruption of this pathway, therefore, provides a novel and effective avenue for therapeutic intervention of breast cancer. Various phytochemicals found in the diet kill breast cancer cells in vitro and prevent as well as suppress breast cancer progression in various preclinical animal models. This review examines the value of dietary phytoconstituents in the prevention and treatment of breast cancer through modulation of the intricate and complex process of angiogenesis. In addition, the potential benefits, challenges, and future directions of research on anti-angiogenic dietary phytochemicals in the prevention and intervention of breast cancer are also addressed. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",
"title": "Modulation of angiogenesis by dietary phytoconstituents in the prevention and intervention of breast cancer."
},
{
"docid": "MED-2578",
"text": "The incidence of colonic cancer differs widely between various human populations. It has been suggested that dietary fiber content is of utmost importance and is inversely related to the occurrence of colonic cancer. However, high-fiber diets are not always correlated with low frequency of colonic cancer, suggesting the involvement of additional dietary constituents. Inositol hexaphosphate (phytic acid) is an abundant plant seed component present in many, but not all, fiber-rich diets. The authors have found that phytic acid is a potent inhibitor of iron-mediated generation of the hazardous oxidant, hydroxyl radical. Herein, the authors propose that inhibition of intracolonic hydroxyl radical generation, via the chelation of reactive iron by phytic acid, may help explain the suppression of colonic carcinogenesis and other inflammatory bowel diseases by diets rich in phytic acid.",
"title": "Dietary suppression of colonic cancer. Fiber or phytate?"
},
{
"docid": "MED-2988",
"text": "This review describes the present state of knowledge about phytic acid (phytate), which is often present in legume seeds. The antinutritional effects of phytic acid primarily relate to the strong chelating associated with its six reactive phosphate groups. Its ability to complex with proteins and particularly with minerals has been a subject of investigation from chemical and nutritional viewpoints. The hydrolysis of phytate into inositol and phosphates or phosphoric acid occurs as a result of phytase or nonenzymatic cleavage. Enzymes capable of hydrolysing phytates are widely distributed in micro-organisms, plants and animals. Phytases act in a stepwise manner to catalyse the hydrolysis of phytic acid. To reduce or eliminate the chelating ability of phytate, dephosphorylation of hexa- and penta-phosphate forms is essential since a high degree of phosphorylation is necessary to bind minerals. There are several methods of decreasing the inhibitory effect of phytic acid on mineral absorption (cooking, germination, fermentation, soaking, autolysis). Nevertheless, inositol hexaphosphate is receiving increased attention owing to its role in cancer prevention and/or therapy and its hypocholesterolaemic effect.",
"title": "The role of phytic acid in legumes: antinutrient or beneficial function?"
},
{
"docid": "MED-2585",
"text": "Inositol hexaphosphate (IP6) is a naturally occurring polyphosphorylated carbohydrate that is present in substantial amounts in almost all plant and mammalian cells. It was recently recognized to possess multiple biological functions. A striking anticancer effect of IP6 was demonstrated in different experimental models. Inositol is also a natural constituent possessing moderate anticancer activity. The most consistent and best anticancer results were obtained from the combination of IP6 plus inositol. In addition to reducing cell proliferation, IP6 increases differentiation of malignant cells, often resulting in a reversion to normal phenotype. Exogenously administered IP6 is rapidly taken into the cells and dephosphorylated to lower-phosphate inositol phosphates, which further interfere with signal transduction pathways and cell cycle arrest. Enhanced immunity and antioxidant properties can also contribute to tumor cell destruction. However, the molecular mechanisms underlying this anticancer action are not fully understood. Because it is abundantly present in regular diet, efficiently absorbed from the gastrointestinal tract, and safe, IP6 holds great promise in our strategies for the prevention and treatment of cancer. IP6 plus inositol enhances the anticancer effect of conventional chemotherapy, controls cancer metastases, and improves the quality of life, as shown in a pilot clinical trial. The data strongly argue for the use of IP6 plus inositol in our strategies for cancer prevention and treatment. However, the effectiveness and safety of IP6 plus inositol at therapeutic doses needs to be determined in phase I and phase II clinical trials in humans.",
"title": "Cancer inhibition by inositol hexaphosphate (IP6) and inositol: from laboratory to clinic."
}
] |
[
{
"docid": "MED-3840",
"text": "The incidence of breast cancer is increasing in the Western world and there is an urgent need for studies of the mechanisms of sex steroids in order to develop novel preventive strategies. Diet modifications may be among the means for breast cancer prevention. Angiogenesis, key in tumor progression, is regulated by the balance between pro- and anti-angiogenic factors, which are controlled in the extracellular space. Sampling of these molecules at their bioactive compartment is therefore needed. The aims of this study were to explore if tamoxifen, one of the most used anti-estrogen treatments for breast cancer affected some of the most important endogenous angiogenesis regulators, vascular endothelial growth factor (VEGF), angiogenin, and endostatin in normal breast tissue in vivo and if a diet supplementation with flaxseed had similar effects as tamoxifen in the breast. Microdialysis was used for in situ sampling of extracellular proteins in normal breast tissue of women before and after six weeks of tamoxifen treatment or before and after addition of 25 g/day of ground flaxseed to the diet or in control women. We show significant correlations between estradiol and levels of VEGF, angiogenin, and endostatin in vivo, which was verified in ex vivo breast tissue culture. Moreover, tamoxifen decreased the levels of VEGF and angiogenin in the breast whereas endostatin increased significantly. Flaxseed did not alter VEGF or angiogenin levels but similar to tamoxifen the levels of endostatin increased significantly. We conclude that one of the mechanisms of tamoxifen in normal breast tissue include tipping of the angiogenic balance into an anti-angiogenic state and that flaxseed has limited effects on the pro-angiogenic factors whereas the anti-angiogenic endostatin may be modified by diet. Further studies of diet modifications for breast cancer prevention are warranted.",
"title": "Tamoxifen and Flaxseed Alter Angiogenesis Regulators in Normal Human Breast Tissue In Vivo"
},
{
"docid": "MED-4224",
"text": "Metastatic, rather than primary tumours are responsible for ninety percent cancer deaths. Despite significant advances in the understanding of molecular and cellular mechanisms in tumour metastases, there are limitations in preventive treatment of metastatic tumours. Much evidence arising from laboratory and clinical studies suggests that growth factors and their receptors are implicated in cancer metastases development. We review the origin and production of growth factors and their receptors in all stages of cancer metastases including epithelial-mesenchymal transition, cancer cell invasion and migration, survival within the circulation, seeding at distant organs and metastatic tumour angiogenesis. The functions of growth factors and their receptors are also discussed. This review presents the efforts made in understanding this challenge to aid in the development of new treatment strategies for cancer metastases.",
"title": "Growth Factors and their receptors in cancer metastases."
},
{
"docid": "MED-2818",
"text": "Curcumin is a polyphenol derived from the herbal remedy and dietary spice turmeric. It possesses diverse anti-inflammatory and anti-cancer properties following oral or topical administration. Apart from curcumin's potent antioxidant capacity at neutral and acidic pH, its mechanisms of action include inhibition of several cell signalling pathways at multiple levels, effects on cellular enzymes such as cyclooxygenase and glutathione S-transferases, immuno-modulation and effects on angiogenesis and cell-cell adhesion. Curcumin's ability to affect gene transcription and to induce apoptosis in preclinical models is likely to be of particular relevance to cancer chemoprevention and chemotherapy in patients. Although curcumin's low systemic bioavailability following oral dosing may limit access of sufficient concentrations for pharmacological effect in certain tissues, the attainment of biologically active levels in the gastrointestinal tract has been demonstrated in animals and humans. Sufficient data currently exist to advocate phase II clinical evaluation of oral curcumin in patients with invasive malignancy or pre-invasive lesions of the gastrointestinal tract, particularly the colon and rectum.",
"title": "Curcumin: the story so far."
},
{
"docid": "MED-2817",
"text": "Curcumin (diferuloylmethane), a yellow coloring agent extracted from turmeric is also used as a remedy for the treatment and prevention of inflammatory diseases. Acute and chronic inflammation is a major factor in the progression of obesity, type II diabetes, arthritis, pancreatitis, cardiovascular, neurodegenerative and metabolic diseases, as well as certain types of cancer. Turmeric has a long history of use in Ayurvedic medicine for the treatment of inflammatory disorders. Recent studies on the efficacy and therapeutic applicability of turmeric have suggested that the active ingredient of tumeric is curcumin. Further, compelling evidence has shown that curcumin has the ability to inhibit inflammatory cell proliferation, invasion, and angiogenesis through multiple molecular targets and mechanisms of action. Curcumin is safe, non-toxic, and mediates its anti-inflammatory effects through the down-regulation of inflammatory transcription factors, cytokines, redox status, protein kinases, and enzymes that all promote inflammation. In addition, curcumin induces apoptosis through mitochondrial and receptor-mediated pathways, as well as activation of caspase cascades. In the current study, the anti-inflammatory effects of curcumin were evaluated relative to various chronic inflammatory diseases. Based on the available pharmacological data obtained from in vitro and in vivo research, as well as clinical trials, an opportunity exists to translate curcumin into clinics for the prevention of inflammatory diseases in the near future. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.",
"title": "Curcumin in inflammatory diseases."
},
{
"docid": "MED-2507",
"text": "Increased plasma levels of adiponectin, metformin therapy of diabetes, rapamycin administration in transplant patients, and lifelong consumption of low-protein plant-based diets have all been linked to decreased risk for various cancers. These benefits may be mediated, at least in part, by down-regulated activity of the mTORC1 complex, a key regulator of protein translation. By boosting the effective availability of the translation initiator eIF4E, mTORC1 activity promotes the translation of a number of \"weak\" mRNAs that code for proteins, often up-regulated in cancer, that promote cellular proliferation, invasiveness, and angiogenesis, and that abet cancer promotion and chemoresistance by opposing apoptosis. Measures which inhibit eIF4E activity, either directly or indirectly, may have utility not only for cancer prevention, but also for the treatment of many cancers in which eIF4E drives malignancy. Since eIF4E is overexpressed in many cancers, strategies which target eIF4E directly--some of which are now being assessed clinically--may have the broadest efficacy in this regard. Many of the \"weak\" mRNAs coding for proteins that promote malignant behavior or chemoresistance are regulated transcriptionally by NF-kappaB and/or Stat3, which are active in a high proportion of cancers; thus, regimens concurrently targeting eIF4E, NF-kappaB, and Stat3 may suppress these proteins at both the transcriptional and translational levels, potentially achieving a very marked reduction in their expression. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "mTORC1 activity as a determinant of cancer risk--rationalizing the cancer-preventive effects of adiponectin, metformin, rapamycin, and low-protein ..."
},
{
"docid": "MED-2824",
"text": "Cancer is primarily a disease of old age, and that life style plays a major role in the development of most cancers is now well recognized. While plant-based formulations have been used to treat cancer for centuries, current treatments usually involve poisonous mustard gas, chemotherapy, radiation, and targeted therapies. While traditional plant-derived medicines are safe, what are the active principles in them and how do they mediate their effects against cancer is perhaps best illustrated by curcumin, a derivative of turmeric used for centuries to treat a wide variety of inflammatory conditions. Curcumin is a diferuloylmethane derived from the Indian spice, turmeric (popularly called \"curry powder\") that has been shown to interfere with multiple cell signaling pathways, including cell cycle (cyclin D1 and cyclin E), apoptosis (activation of caspases and down-regulation of antiapoptotic gene products), proliferation (HER-2, EGFR, and AP-1), survival (PI3K/AKT pathway), invasion (MMP-9 and adhesion molecules), angiogenesis (VEGF), metastasis (CXCR-4) and inflammation (NF-kappaB, TNF, IL-6, IL-1, COX-2, and 5-LOX). The activity of curcumin reported against leukemia and lymphoma, gastrointestinal cancers, genitourinary cancers, breast cancer, ovarian cancer, head and neck squamous cell carcinoma, lung cancer, melanoma, neurological cancers, and sarcoma reflects its ability to affect multiple targets. Thus an \"old-age\" disease such as cancer requires an \"age-old\" treatment.",
"title": "Curcumin and cancer: an \"old-age\" disease with an \"age-old\" solution."
},
{
"docid": "MED-2922",
"text": "Overwhelming evidence suggests that edible small and soft-fleshed berry fruits may have beneficial effects against several types of human cancers. The anticancer potential of berries has been related, at least in part, to a multitude of bioactive phytochemicals that these colorful fruits contain, including polyphenols (flavonoids, proanthocyanidins, ellagitannins, gallotannins, phenolic acids), stilbenoids, lignans, and triterpenoids. Studies show that the anticancer effects of berry bioactives are partially mediated through their abilities to counteract, reduce, and also repair damage resulting from oxidative stress and inflammation. In addition, berry bioactives also regulate carcinogen and xenobiotic metabolizing enzymes, various transcription and growth factors, inflammatory cytokines, and subcellular signaling pathways of cancer cell proliferation, apoptosis, and tumor angiogenesis. Berry phytochemicals may also potentially sensitize tumor cells to chemotherapeutic agents by inhibiting pathways that lead to treatment resistance, and berry fruit consumption may provide protection from therapy-associated toxicities. Although a wide variety of berry fruits are consumed worldwide, this paper focuses on those commonly consumed in North America, namely, blackberries, black raspberries, blueberries, cranberries, red raspberries, and strawberries. In addition, a large body of studies on singly purified berry bioactives is available, but this paper focuses on studies of \"whole berries\" per se, that is, as berry extracts and purified fractions, juices, and freeze-dried powders. Potential mechanisms of anticancer action and bioavailability of berry phenolics, as well as gaps in knowledge and recommendations for future berry research, are also briefly discussed.",
"title": "Berry fruits for cancer prevention: current status and future prospects."
},
{
"docid": "MED-2357",
"text": "Patients with cancer have circulating heterophile antibodies that agglutinate animal red cells via recognition of the mammalian cell surface sialic acid N-glycolylneuraminic acid (Neu5Gc), which was long considered an oncofetal antigen in humans. However, humans are genetically deficient in Neu5Gc production and instead metabolically accumulate Neu5Gc from dietary sources, particularly red meats and milk products. Moreover, mice with a human-like defect showed no alternate pathway for Neu5Gc synthesis and even normal humans express anti-Neu5Gc antibodies. We show here that human tumors accumulate Neu5Gc that is covalently attached to multiple classes of glycans. The paradox of human tumor Neu5Gc accumulation in the face of circulating anti-Neu5Gc antibodies was hypothesized to be due to facilitation of tumor progression by the resulting low-grade chronic inflammation. Indeed, murine tumors expressing human-like levels of Neu5Gc show accelerated growth in syngeneic mice with a human-like Neu5Gc deficiency, coincident with the induction of anti-Neu5Gc antibodies and increased infiltration of inflammatory cells. Transfer of polyclonal monospecific syngeneic mouse anti-Neu5Gc serum also enhanced growth of transplanted syngeneic tumors bearing human-like levels of Neu5Gc, with tumors showing evidence for antibody deposition, enhanced angiogenesis and chronic inflammation. These effects were suppressed by a cyclooxygenase-2 inhibitor, a drug type known to reduce human carcinoma risk. Finally, affinity-purified human anti-Neu5Gc antibodies also accelerate growth of Neu5Gc-containing tumors in Neu5Gc-deficient mice. Taken together, the data suggest that the human propensity to develop diet-related carcinomas is contributed to by local chronic inflammation, resulting from interaction of metabolically-accumulated dietary Neu5Gc with circulating anti-Neu5Gc antibodies.",
"title": "Evidence for a human-specific mechanism for diet and antibody-mediated inflammation in carcinoma progression"
},
{
"docid": "MED-3878",
"text": "Diet, nutritional status, and certain dietary supplements are postulated to influence the development and progression of prostate cancer. Angiogenesis and inflammation are central to tumor growth and progression, but the effect of diet on these processes remains uncertain. We explored changes in 50 plasma cytokines and angiogenic factors (CAFs) in 145 men with prostate cancer enrolled in a pre-operative, randomized controlled phase-II trial with four arms: control (usual diet); low-fat (LF) diet; flaxseed-supplemented (FS) diet; and flaxseed-supplemented, low-fat diet. The mean duration of dietary intervention was 30–31 days. Among the individual arms, the largest number of significant changes (baseline vs pre-operative follow-up) was observed in the LF arm, with 19 CAFs decreasing and one increasing (p<.05). Compared to the control arm, 6 CAFs—including pro-angiogenic factors (stromal-cell derived-1α and myeloid factors (granulocyte-colony-stimulating factor, macrophage colony-stimulating factor — all decreased in the LF arm compared to controls; 3 and 4 CAFs changed in the FS and FS+LF arms, respectively. Weight loss occurred in the LF arms and significantly correlated with VEGF decreases (P <0.001). The CAFs that changed in the LF arm are all known to be regulated by nuclear factor-kappa B (NF-κB), and a pathway analysis identified NF-κB as the most likely regulatory network associated with these changes in the LF arm, but not in the FS-containing arms. These results suggest that a low-fat diet without flaxseed may reduce levels of specific inflammatory cytokines and angiogenic factors and suggests that the NF-κB pathway may be a mediator of these changes.",
"title": "Effect of Low-fat Diets on Plasma Levels of NFκB-regulated Inflammatory Cytokines and Angiogenic Factors in Men with Prostate Cancer"
},
{
"docid": "MED-3721",
"text": "Reduced expression of proapoptotic and terminal differentiation genes in conjunction with increased levels of the proinflammatory and angiogenesis-inducing enzymes, cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS), correlate with malignant transformation of oral intraepithelial neoplasia (IEN). Accordingly, this study investigated the effects of a 10% (w/w) freeze-dried black raspberry gel on oral IEN histopathology, gene expression profiles, intraepithelial COX-2 and iNOS proteins, and microvascular densities. Our laboratories have shown that freeze-dried black raspberries possess antioxidant properties and also induce keratinocyte apoptosis and terminal differentiation. Oral IEN tissues were hemisected to provide samples for pretreatment diagnoses and establish baseline biochemical and molecular variables. Treatment of the remaining lesional tissue (0.5 g gel applied four times daily for 6 weeks) began 1 week after the initial biopsy. RNA was isolated from snap-frozen IEN lesions for microarray analyses, followed by quantitative reverse transcription-PCR validation. Additional epithelial gene-specific quantitative reverse transcription-PCR analyses facilitated the assessment of target tissue treatment effects. Surface epithelial COX-2 and iNOS protein levels and microvascular densities were determined by image analysis quantified immunohistochemistry. Topical berry gel application uniformly suppressed genes associated with RNA processing, growth factor recycling, and inhibition of apoptosis. Although the majority of participants showed posttreatment decreases in epithelial iNOS and COX-2 proteins, only COX-2 reductions were statistically significant. These data show that berry gel application modulated oral IEN gene expression profiles, ultimately reducing epithelial COX-2 protein. In a patient subset, berry gel application also reduced vascular densities in the superficial connective tissues and induced genes associated with keratinocyte terminal differentiation.",
"title": "Topical Application of a Bioadhesive Black Raspberry Gel Modulates Gene Expression and Reduces Cyclooxygenase 2 Protein in Human Premalignant Oral Lesions"
},
{
"docid": "MED-3702",
"text": "BACKGROUND: Increased prevalence of allergic diseases in western societies has been described as an epidemic. The precise turning point for the epidemic and the antigens responsible for it remain obscure. OBJECTIVE: To evaluate how the prevalence of atopic disease has changed in terms of detectable sensitization to aeroallergens and dietary allergens in a cross-sectional comparison of subjects from birth cohorts more than 60 years apart. METHODS: We studied four groups of 100 subjects each (at ages 7, 27, 47 and 67 years), representing those born in 1990, 1963-66, 1943-46 and in 1923-26, respectively. Serum total and specific IgE concentrations against aeroallergens and dietary allergens were determined. A questionnaire elicited information on symptoms, allergic diseases and medication. RESULTS: The proportion of subjects with detectable IgE antibodies against aeroallergens increased consistently from the oldest to the youngest birth cohorts; chi2 trend=56.809, P<0.0001. Similar progression was not seen in sensitization to dietary allergens. The proportion of those with diagnosed asthma differed significantly (chi2=13.45, P=0.004) across the birth cohorts. The lowest prevalence of asthma and sensitization to dietary allergens was detected in those born in 1943-46, i.e. during or immediately after World War II. CONCLUSION: Prevalence of sensitization to airborne allergens, unlike that to dietary allergens, has increased over a long period of time. Our results support the concept of the immune function being programmed by external factors early in life. They also call for caution when interpretations of the pace and possible causes of the allergy epidemic are made on the basis of short-term studies.",
"title": "The allergy epidemic extends beyond the past few decades."
},
{
"docid": "MED-3541",
"text": "OBJECTIVE: The study evaluated the association between consumption frequencies of the major food categories and the risk of new depression four years later in older Taiwanese. DESIGN: A prospective cohort study with multistage random sampling. Logistic regression analysis evaluated the significance of the longitudinal associations of intake frequencies of the major food categories with future (4 years later) risk of new depression, controlled for possible confounding factors with or without adjustment for cognitive status. SETTING: Population-based free-living elderly. SUBJECTS: Men and women (n 1609) ≥65 years of age. RESULTS: In a regression model that controlled for demographic, socio-economic, lifestyle and disease/health-related variables but not cognitive status, both fruits (OR = 0·66, 95 % CI 0·45, 0·98, P = 0·038) and vegetables (OR = 0·38, 95 % CI 0·17, 0·86, P = 0·021) were protective against depressive symptoms 4 years later. However, when the same regression model was also adjusted for cognitive status, only vegetables (OR = 0·40, 95 % CI 0·17, 0·95, P = 0·039) were protective against depressive symptoms. Higher consumption of eggs was close to being significant in both regression models (P = 0·087 and 0·069, respectively). Other food categories including meat/poultry, fish, seafood, dairy, legumes, grains and tea showed no significant associations. CONCLUSIONS: Results suggest that although confounding factors cannot be totally ruled out, more frequent consumption of vegetables seems to be protective against depressive symptoms in the elderly. Further studies are needed to elucidate the causal role and the mechanism of the association.",
"title": "Frequent consumption of vegetables predicts lower risk of depression in older Taiwanese - results of a prospective population-based study."
},
{
"docid": "MED-5122",
"text": "BACKGROUND: Drinking mate has been associated with cancers of the esophagus, oropharynx, larynx, lung, kidney, and bladder. We conducted this study to determine whether drinking mate could lead to substantial exposure to polycyclic aromatic hydrocarbons (PAH), including known carcinogens, such as benzo[a]pyrene. METHODS: The concentrations of 21 individual PAHs were measured in dry leaves of eight commercial brands of yerba mate and in infusions made with hot (80 degrees C) or cold (5 degrees C) water. Measurements were done using gas chromatography/mass spectrometry, with deuterated PAHs as the surrogates. Infusions were made by adding water to the leaves, removing the resulting infusion after 5 min, and then adding more water to the remaining leaves. This process was repeated 12 times for each infusion temperature. RESULTS: The total concentrations of the 21 PAHs in different brands of yerba mate ranged from 536 to 2,906 ng/g dry leaves. Benzo[a]pyrene concentrations ranged from 8.03 to 53.3 ng/g dry leaves. For the mate infusions prepared using hot water and brand 1, 37% (1,092 of 2,906 ng) of the total measured PAHs and 50% (25.1 of 50 ng) of the benzo[a]pyrene content were released into the 12 infusions. Similar results were obtained for other hot and cold infusions. CONCLUSION: Very high concentrations of carcinogenic PAHs were found in yerba mate leaves and in hot and cold mate infusions. Our results support the hypothesis that the carcinogenicity of mate may be related to its PAH content.",
"title": "High levels of carcinogenic polycyclic aromatic hydrocarbons in mate drinks."
},
{
"docid": "MED-4722",
"text": "BACKGROUND: There has been a resurgence of interest in the controversial relation between dietary protein and bone health. OBJECTIVE: This article reports on the first systematic review and meta-analysis of the relation between protein and bone health in healthy human adults. DESIGN: The MEDLINE (January 1966 to September 2007) and EMBASE (1974 to July 2008) databases were electronically searched for all relevant studies of healthy adults; studies of calcium excretion or calcium balance were excluded. RESULTS: In cross-sectional surveys, all pooled r values for the relation between protein intake and bone mineral density (BMD) or bone mineral content at the main clinically relevant sites were significant and positive; protein intake explained 1-2% of BMD. A meta-analysis of randomized placebo-controlled trials indicated a significant positive influence of all protein supplementation on lumbar spine BMD but showed no association with relative risk of hip fractures. No significant effects were identified for soy protein or milk basic protein on lumbar spine BMD. CONCLUSIONS: A small positive effect of protein supplementation on lumbar spine BMD in randomized placebo-controlled trials supports the positive association between protein intake and bone health found in cross-sectional surveys. However, these results were not supported by cohort study findings for hip fracture risk. Any effects found were small and had 95% CIs that were close to zero. Therefore, there is a small benefit of protein on bone health, but the benefit may not necessarily translate into reduced fracture risk in the long term.",
"title": "Dietary protein and bone health: a systematic review and meta-analysis."
},
{
"docid": "MED-1118",
"text": "OBJECTIVE: To measure Proteus mirabilis and Escherichia coli antibody levels in patients with rheumatoid arthritis (RA) during treatment by vegetarian diet. METHODS: Sera were collected from 53 RA patients who took part in a controlled clinical trial of fasting and a one year vegetarian diet. P mirabilis and E coli antibody levels were measured by an indirect immunofluorescence technique and an enzyme immunoassay, respectively. RESULTS: The patients on the vegetarian diet had a significant reduction in the mean anti-proteus titres at all time points during the study, compared with baseline values (all p < 0.05). No significant change in titre was observed in patients who followed an omnivorous diet. The decrease in anti-proteus titre was greater in the patients who responded well to the vegetarian diet compared with diet non-responders and omnivores. The total IgG concentration and levels of antibody against E coli, however, were almost unchanged in all patient groups during the trial. The decrease from baseline in proteus antibody levels correlated significantly (p < 0.001) with the decrease in a modified Stoke disease activity index. CONCLUSION: The decrease in P mirabilis antibody levels in the diet responders and the correlation between the decrease in proteus antibody level and decrease in disease activity supports the suggestion of an aetiopathogenetic role for P mirabilis in RA.",
"title": "Decrease in anti-Proteus mirabilis but not anti-Escherichia coli antibody levels in rheumatoid arthritis patients treated with fasting and a one year vegetarian diet."
},
{
"docid": "MED-3177",
"text": "Neurocysticercosis (NCC) is an infection of the central nervous system (CNS) caused by the metacestode larval form of the parasite Taenia sp. Many factors can contribute to the endemic nature of cysticercosis. The inflammatory process that occurs in the tissue surrounding the parasite and/or distal from it can result from several associated mechanisms and may be disproportionate with the number of cysts. This discrepancy may lead to difficulty with the proper diagnosis in people from low endemic regions or regions that lack laboratory resources. In the CNS, the cysticerci have two basic forms, isolated cysts (Cysticercus cellulosae=CC) and racemose cysts (Cysticercus racemosus=CR), and may be meningeal, parenchymal, or ventricular or have a mixed location. The clinical manifestations are based on two fundamental syndromes that may occur in isolation or be associated: epilepsy and intracranial hypertension. They may be asymptomatic, symptomatic or fatal; have an acute, sub-acute or chronic picture; or may be in remission or exacerbated. The cerebrospinal fluid (CSF) may be normal, even in patients with viable cysticerci, until the patients begin to exhibit the classical syndrome of NCC in the CSF, or show changes in one or more routine analysed parameters. Computed tomography (CT) and magnetic resonance imaging (MRI) have allowed non-invasive diagnoses, but can lead to false negatives. Treatment is a highly controversial issue and is characterised by individualised therapy sessions. Two drugs are commonly used, praziquantel (PZQ) and albendazole (ABZ). The choice of anti-inflammatory drugs includes steroids and dextrochlorpheniramine (DCP). Hydrocephalus is a common secondary effect of NCC. Surgical cases of hydrocephalus must be submitted to ventricle-peritoneal shunt (VPS) immediately before cysticidal treatment, and surgical extirpation of the cyst may lead to an absence of the surrounding inflammatory process. The progression of NCC may be simple or complicated, have remission with or without treatment and may exhibit symptoms that can disappear for long periods of time or persist until death. Unknown, neglected and controversial aspects of NCC, such as the impaired fourth ventricle syndrome, the presence of chronic brain oedema and psychic complaints, in addition to the lack of detectable glucose in the CSF and re-infection are discussed.",
"title": "Neurocysticercosis: the enigmatic disease."
},
{
"docid": "MED-4351",
"text": "The past decade has seen an explosion in research focusing on innate immunity. Through a wide range of mechanisms including phagocytosis, intracellular killing, and activation of pro-inflammatory or antiviral cytokine production via pattern recognition receptors, the cells of the innate immune system initiate and support adaptive immunity. The effects of aging on innate immune responses remain incompletely understood, particularly in humans. Here, we review advances in the study of human immunosenescence in the diverse cells of the innate immune system, including neutrophils, monocytes, macrophages, NK and NKT cells, and dendritic cells—with a focus on consequences for the response to infection or vaccination in old age.",
"title": "Human innate Immunosenescence: causes and consequences for immunity in old age"
},
{
"docid": "MED-1038",
"text": "We examined effects of fiber on stool output, since this is one of the primary mediating variables for the hypothesized relationship between fiber and disease. Total neutral detergent fiber in the dietary fiber source was predictive of stool weight but not frequency. Substantial individual differences in stool output remained when dietary factors were controlled. Personality measures were used to predict stool weight and frequency independently of diet, and accounted for about as much variance in stool output as did dietary fiber. These results suggest that personality factors predispose some persons to low stool output. These individuals may benefit particularly from dietary fiber.",
"title": "Dietary fiber and personality factors as determinants of stool output."
},
{
"docid": "MED-983",
"text": "BACKGROUND: Our goal was to forecast the global burden of Alzheimer's disease and evaluate the potential impact of interventions that delay disease onset or progression. METHODS: A stochastic, multistate model was used in conjunction with United Nations worldwide population forecasts and data from epidemiological studies of the risks of Alzheimer's disease. RESULTS: In 2006, the worldwide prevalence of Alzheimer's disease was 26.6 million. By 2050, the prevalence will quadruple, by which time 1 in 85 persons worldwide will be living with the disease. We estimate about 43% of prevalent cases need a high level of care, equivalent to that of a nursing home. If interventions could delay both disease onset and progression by a modest 1 year, there would be nearly 9.2 million fewer cases of the disease in 2050, with nearly the entire decline attributable to decreases in persons needing a high level of care. CONCLUSIONS: We face a looming global epidemic of Alzheimer's disease as the world's population ages. Modest advances in therapeutic and preventive strategies that lead to even small delays in the onset and progression of Alzheimer's disease can significantly reduce the global burden of this disease.",
"title": "Forecasting the global burden of Alzheimer's disease."
},
{
"docid": "MED-2757",
"text": "BACKGROUND: Multivitamins are the most commonly used supplement in the developed world. Recent epidemiologic findings suggest that multivitamin use increases the risk of mortality. OBJECTIVE: We aimed to determine whether multivitamin-multimineral treatment, used for primary or secondary prevention, increases the risk of mortality in independently living adults. DESIGN: We performed a meta-analysis of randomized controlled trials. Multiple electronic databases were systematically searched from March to October 2012. Randomized controlled primary or secondary prevention trials were considered for inclusion. Eligible trials investigated daily multivitamin-multimineral supplementation for ≥1 y. Cohorts described as institutionalized or as having terminal illness (tertiary prevention) were excluded. The number of deaths and the sample size of each study arm were extracted independently by 2 researchers. Twenty-one articles were included in the analysis, which generated a total pooled sample of 91,074 people and 8794 deaths. These trials were pooled in a meta-analysis, and the outcomes were expressed as RRs and 95% CIs. RESULTS: The average age of the pooled sample was 62 y, and the average duration of supplementation was 43 mo. Across all studies, no effect of multivitamin-multimineral treatment on all-cause mortality (RR: 0.98; 95% CI: 0.94, 1.02) was observed. There was a trend for a reduced risk of all-cause mortality across primary prevention trials (RR: 0.94; 95% CI: 0.89, 1.00). Multivitamin-multimineral treatment had no effect on mortality due to vascular causes (RR: 1.01; 95% CI: 0.93, 1.09) or cancer (RR: 0.96; 95% CI: 0.88, 1.04). No statistical evidence of heterogeneity or publication bias was observed. CONCLUSION: Multivitamin-multimineral treatment has no effect on mortality risk.",
"title": "Multivitamin-multimineral supplementation and mortality: a meta-analysis of randomized controlled trials."
},
{
"docid": "MED-1200",
"text": "Oxidative stress has been implicated in the pathophysiology of many neuropsychiatric disorders such as schizophrenia, bipolar disorder, major depression etc. Both genetic and nongenetic factors have been found to cause increased cellular levels of reactive oxygen species beyond the capacity of antioxidant defense mechanism in patients of psychiatric disorders. These factors trigger oxidative cellular damage to lipids, proteins and DNA, leading to abnormal neural growth and differentiation. Therefore, novel therapeutic strategies such as supplementation with antioxidants can be effective for long-term treatment management of neuropsychiatric disorders. The use of antioxidants and PUFAs as supplements in the treatment of neuropsychiatric disorders has provided some promising results. At the same time, one should be cautious with the use of antioxidants since excessive antioxidants could dangerously interfere with some of the protective functions of reactive oxygen species. The present article will give an overview of the potential strategies and outcomes of using antioxidants as therapeutics in psychiatric disorders.",
"title": "Antioxidants as potential therapeutics for neuropsychiatric disorders"
},
{
"docid": "MED-1131",
"text": "To clarify the role of the faecal flora in the diet-induced decrease of rheumatoid arthritis (RA) activity, 43 RA patients were randomized into two groups: the test group to receive living food, a form of uncooked vegan diet rich in lactobacilli, and the control group to continue their ordinary omnivorous diets. Based on clinical assessments before, during and after the intervention period, a disease improvement index was constructed for each patient. According to the index, patients were assigned either to a group with a high improvement index (HI) or to a group with a low improvement index (LO). Stool samples collected from each patient before the intervention and at 1 month were analysed by direct stool sample gas-liquid chromatography of bacterial cellular fatty acids. This method has proved to be a simple and sensitive way to detect changes and differences in the faecal microbial flora between individual stool samples or groups of them. A significant, diet-induced change in the faecal flora (P = 0.001) was observed in the test group, but not in the control group. Further, in the test group, a significant (P = 0.001) difference was detected between the HI and LO categories at 1 month, but not in the pre-test samples. We conclude that a vegan diet changes the faecal microbial flora in RA patients, and changes in the faecal flora are associated with improvement in RA activity.",
"title": "Faecal microbial flora and disease activity in rheumatoid arthritis during a vegan diet."
},
{
"docid": "MED-1786",
"text": "Fertility status may predict later mortality, but no studies have examined the effect of semen quality on subsequent mortality. Men referred to the Copenhagen Sperm Analysis Laboratory by general practitioners and urologists from 1963 to 2001 were, through a unique personal identification number, linked to the Danish central registers that hold information on all cases of cancer, causes of death, and number of children in the Danish population. The men were followed until December 31, 2001, death, or censoring, whichever occurred first, and the total mortality and cause-specific mortality of the cohort were compared with those of all age-standardized Danish men or according to semen characteristics. Among 43,277 men without azospermia referred for infertility problems, mortality decreased as the sperm concentration increased up to a threshold of 40 million/mL. As the percentages of motile and morphologically normal spermatozoa and semen volume increased, mortality decreased in a dose-response manner (P(trend) < 0.05). The decrease in mortality among men with good semen quality was due to a decrease in a wide range of diseases and was found among men both with and without children; therefore, the decrease in mortality could not be attributed solely to lifestyle and/or social factors. Semen quality may therefore be a fundamental biomarker of overall male health.",
"title": "Good semen quality and life expectancy: a cohort study of 43,277 men."
},
{
"docid": "MED-5361",
"text": "OBJECTIVE: To compare 2 omega-3 (n-3) preparations enriched with eicosapentaenoic acid (EPA) versus docosahexaenoic acid (DHA) as monotherapy for major depressive disorder (MDD) in a 2-site, placebo-controlled, randomized, double-blind clinical trial. METHOD: 196 adults (53% female; mean [SD] age = 44.7 [13.4] years) with DSM-IV MDD and a baseline 17-item Hamilton Depression Rating Scale (HDRS-17) score ≥ 15 were randomized equally from May 18, 2006, to June 30, 2011, to 8 weeks of double-blind treatment with oral EPA-enriched n-3 1000 mg/d, DHA-enriched n-3 1,000 mg/d, or placebo. RESULTS: 154 subjects completed the study. Modified intent-to-treat (mITT) analysis (n = 177 subjects with ≥ 1 postbaseline visit; 59.3% female, mean [SD] age 45.8 [12.5] years) employed mixed-model repeated measures (MMRM). All 3 groups demonstrated statistically significant improvement in the HDRS-17 (primary outcome measure), 16-item Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR-16), and Clinical Global Improvement-Severity Scale (CGI-S) (P < .05), but neither n-3 preparation separated from placebo (P > .05). Response and remission rates were in the range of 40%-50% and 30%, respectively, for all treatments, with no significant differences between groups. One subject receiving EPA-enriched n-3 discontinued due to worsening depression, and 1 subject receiving placebo discontinued due to an unspecified \"negative reaction\" to pills. CONCLUSIONS: Neither EPA-enriched nor DHA-enriched n-3 was superior to placebo for the treatment of MDD. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00517036. © Copyright 2015 Physicians Postgraduate Press, Inc.",
"title": "A double-blind, randomized controlled clinical trial comparing eicosapentaenoic acid versus docosahexaenoic acid for depression."
},
{
"docid": "MED-2658",
"text": "The prevalence of allergic diseases has increased in recent decades. Allergic diseases, particularly asthma, are complex diseases with strong gene-environment interactions. Epidemiological studies have identified a variety of risk factors for the development of allergic diseases. Among them, endocrine-disrupting chemicals (EDCs) play an important role in triggering or exacerbating these diseases. 4-Nonylphenol (NP) and 4-octylphenol (OP)--two major alkylphenols--have been recognized as common toxic and xenobiotic endocrine disrupters. Due to their low solubility, high hydrophobicity, and low estrogenic activity, they tend to accumulate in the human body and may be associated with the adverse effects of allergic diseases. Recently, new evidence has supported the importance of alkylphenols in the in vitro allergic response. This review focuses on the effects of alkylphenols on several key cell types in the context of allergic inflammation. Copyright © 2012. Published by Elsevier B.V.",
"title": "Alkylphenols--potential modulators of the allergic response."
},
{
"docid": "MED-3637",
"text": "There are over 750 species of bacteria that inhabit the human oral cavity, but only a small fraction of those are attributed to causing plaque-related diseases such as caries. Streptococcus mutans is accepted as the main cariogenic agent and there is substantial knowledge regarding the specific virulence factors that render the organism a pathogen. There has been rising interest in alternative, target-specific treatment options as opposed to nonspecific mechanical plaque removal or application of broad-spectrum antibacterials that are currently in use. The impact of diet on oral health is undeniable, and this is directly observable in populations that consume high quantities of polyphenol-rich foods or beverages. Such populations have low caries incidence and better overall oral health. Camellia sinensis, the plant from which various forms of tea are derived, and Vaccinium macrocarpon (American cranberry fruit) have received notable attention both for their prevalence in the human diet as well as for their unique composition of polyphenols. The biologically active constituents of these plants have demonstrated potent enzyme-inhibitory properties without being bactericidal, a key quality that is important in developing therapies that will not cause microorganisms to develop resistance. The aim of this review is to consider studies that have investigated the feasibility of tea, cranberry, and other select plant derivatives as a potential basis for alternative therapeutic agents against Streptococcus mutans and to evaluate their current and future clinical relevance.",
"title": "Antimicrobial Traits of Tea- and Cranberry-Derived Polyphenols against Streptococcus mutans"
},
{
"docid": "MED-3981",
"text": "The aim of this study was to investigate the relationship between child characteristics, parental and environmental factors and the occurrence of acute respiratory illness (ARI) and acute otitis media (AOM) among Finnish children attending day care centres (DCCs). The study was a cross-sectional questionnaire of 594 children aged 1-6 y from 18 DCCs in Helsinki, Finland. Recurrent (> or =4 diseases/y) ARI was present in 44% of the 1-3-y-olds and 23% of the 4-6-y-olds, and recurrent AOM in 15% and 2.5%, respectively. Parent atopic disease (odds ratio (OR) 1.53, p = 0.033), mother's academic education (OR 1.77, p = 0.008) and a medium length of DCC attendance compared to a short period (OR 1.67, p = 0.049) increased, while furry pets (OR 0.44, p = 0.003) and older child age (OR 0.38, p < 0.001) reduced the risk of recurrent ARI. Recurrent ARI (OR 3.96, p = 0.008), mother's academic education (OR 5.02, p = 0.003), and a medium length of DCC attendance compared to a short period (OR 3.34, p = 0.044) increased, while partial breastfeeding > or =6 months (OR 0.20, p = 0.002) and older child age (OR 0.05, p < 0.001) reduced the risk of recurrent AOM. Parental and environmental factors had a significant impact on recurrent ARI and AOM episodes in children attending DCCs. These risk factors should be considered in future studies intending to reduce DCC infections.",
"title": "Factors associated with acute respiratory illness in day care children."
},
{
"docid": "MED-719",
"text": "In addition to causing embarrassment and unease, flatulence is linked to a variety of symptoms, some of which may be distressing. This review describes the origins of intestinal gas, its composition and methods which have been developed for its analysis. Emphasis is placed upon the effects of legumes in the diet in producing excessive intestinal gas and, particularly, on the role of raffinose-type oligosaccharides, containing alpha-galactosidic groupings. Suggestions for overcoming the problem are presented, including drug treatment, enzyme treatment, food processing and plant breeding. It is emphasised that removal of all raffinose-oligosaccharides from beans does not remove the problem of flatulence in animals and man; the compounds responsible--though assumed to be polysaccharides (or polysaccharide-derived oligomers formed by processing or cooking)--have yet to be characterised.",
"title": "Flatulence--causes, relation to diet and remedies."
},
{
"docid": "MED-2272",
"text": "To assess the physiologic effects of cherry consumption, we measured plasma urate, antioxidant and inflammatory markers in 10 healthy women who consumed Bing sweet cherries. The women, age 22-40 y, consumed two servings (280 g) of cherries after an overnight fast. Blood and urine samples were taken before the cherry dose, and at 1.5, 3 and 5 h postdose. Plasma urate decreased 5 h postdose, mean +/- SEM = 183 +/- 15 micro mol/L compared with predose baseline of 214 +/- 13 micro mol/L (P < 0.05). Urinary urate increased postdose, with peak excretion of 350 +/- 33 micro mol/mmol creatinine 3 h postdose compared with 202 +/- 13 at baseline (P < 0.01). Plasma C-reactive protein (CRP) and nitric oxide (NO) concentrations had decreased marginally 3 h postdose (P < 0.1), whereas plasma albumin and tumor necrosis factor-alpha were unchanged. The vitamin C content of the cherries was solely as dehydroascorbic acid, but postdose increases in plasma ascorbic acid indicated that dehydroascorbic acid in fruits is bioavailable as vitamin C. The decrease in plasma urate after cherry consumption supports the reputed anti-gout efficacy of cherries. The trend toward decreased inflammatory indices (CRP and NO) adds to the in vitro evidence that compounds in cherries may inhibit inflammatory pathways.",
"title": "Consumption of cherries lowers plasma urate in healthy women."
},
{
"docid": "MED-2117",
"text": "Recent evidence underlines the role of Western diet in the pathogenesis of acne. Acne is absent in populations consuming Palaeolithic diets with low glycaemic load and no consumption of milk or dairy products. Two randomized controlled studies, one of which is presented in this issue of Acta Dermato-Venereologica, have provided evidence for the beneficial therapeutic effects of low glycaemic load diets in acne. Epidemiological evidence confirms that milk consumption has an acne-promoting or acne-aggravating effect. Recent progress in understanding the nutrient-sensitive kinase mammalian target of rapamycin complex 1 (mTORC1) allows a new view of nutrient signalling in acne by both high glycaemic load and increased insulin-, IGF-1-, and leucine signalling due to milk protein consumption. Acne should be regarded as an mTORC1-driven disease of civilization, like obesity, type 2 diabetes and cancer induced by Western diet. Early dietary counselling of teenage acne patients is thus a great opportunity for dermatology, which will not only help to improve acne but may reduce the long-term adverse effects of Western diet on more serious mTORC1-driven diseases of civilization.",
"title": "Diet in acne: further evidence for the role of nutrient signalling in acne pathogenesis."
}
] |
PLAIN-3369
|
The Healthiest Beverage
|
[
{
"docid": "MED-2827",
"text": "Alternative and complementary therapeutic approaches, such as the use of a wide array of herbal, nutritional, and physical manipulations, are becoming popular for relieving symptoms of osteoarthritis (OA). The present study evaluated the efficacy of soy protein (SP) supplementation in relieving the pain and discomfort associated with OA. One hundred and thirty-five free-living individuals (64 men and 71 women) with diagnosed OA or with self-reported chronic knee joint pain not attributed to injury or rheumatoid arthritis were recruited for this double-blind, placebo-controlled, parallel design study. Study participants were assigned randomly to consume 40 g of either supplemental SP or milk-based protein (MP) daily for 3 months. Pain, knee range of motion, and overall physical activity were evaluated prior to the start of treatment and monthly thereafter. Serum levels of glycoprotein 39 (YKL-40), a marker of cartilage degradation, and insulin-like growth factor-I (IGF-I), a growth factor associated with cartilage synthesis, were assessed at baseline and at the end of the study. Overall, SP improved OA-associated symptoms such as range of motion and several factors associated with pain and quality of life in comparison to MP. However, these beneficial effects were mainly due to the effect of SP in men rather than women. Biochemical markers of cartilage metabolism further support the efficacy of SP in men as indicated by a significant increase in serum level of IGF-I and a significant decrease in serum level of YKL-40 compared to MP. This study is the first to provide evidence of possible beneficial effects of SP in the management of OA. Examining and verifying the long-term effects of SP on improving symptoms of OA, particularly in men, is warranted.",
"title": "Soy protein may alleviate osteoarthritis symptoms."
},
{
"docid": "MED-5052",
"text": "OBJECTIVE: Habitual green tea consumption has long been associated with health benefits including chemoprevention and cardiovascular protection. This non-systematic literature review presents the clinical evidence to date. METHOD: A literature review of peer-reviewed articles on observational and interventional studies was conducted to include green tea, its extract or its purified polyphenol (-)-epigallocatechin-3-gallate (EGCG). Electronic databases searched included PubMed (1966-2009) and the Cochrane Library (Issue 4, 2008). RESULTS: Observational studies are inconclusive on the benefits of habitual consumption of green tea in the prevention of most cancers. However, there are trends towards prevention in breast and prostate cancers. Interventional studies have demonstrated reduction in relapses following surgical resection in colorectal adenomas and increased survival rates in epithelial ovarian cancer. Observational studies indicate that green tea may provide protection against hypertension and reduce the risk for stroke, and interventional studies are providing biochemical and physiological evidence. CONCLUSION: Although the overall clinical evidence is inconclusive, habitual green tea consumption may be providing some level of chemoprevention in prostate and breast cancer. Green tea may also attenuate the risk factors association with the development of atherosclerosis thus reducing the incidence of cardiovascular events and stoke.",
"title": "Can green tea do that? A literature review of the clinical evidence."
},
{
"docid": "MED-2826",
"text": "Background Curcumin extracts of turmeric are proposed to produce health benefits. To date, human intervention studies have focused mainly on people with existing health problems given high doses of poorly absorbed curcumin. The purpose of the current study was to check whether in healthy people, a low dose of a lipidated curcumin extract could alter wellness-related measures. Methods The present study was conducted in healthy middle aged people (40–60 years old) with a low dose of curcumin (80 mg/day) in a lipidated form expected to have good absorption. Subjects were given either curcumin (N = 19) or placebo (N = 19) for 4 wk. Blood and saliva samples were taken before and after the 4 weeks and analyzed for a variety of blood and saliva measures relevant to health promotion. Results Curcumin, but not placebo, produced the following statistically significant changes: lowering of plasma triglyceride values, lowering of salivary amylase levels, raising of salivary radical scavenging capacities, raising of plasma catalase activities, lowering of plasma beta amyloid protein concentrations, lowering of plasma sICAM readings, increased plasma myeloperoxidase without increased c-reactive protein levels, increased plasma nitric oxide, and decreased plasma alanine amino transferase activities. Conclusion Collectively, these results demonstrate that a low dose of a curcumin-lipid preparation can produce a variety of potentially health promoting effects in healthy middle aged people.",
"title": "Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people"
},
{
"docid": "MED-2830",
"text": "OBJECTIVE: The aim of this work was to determine the bioavailability of herbs and spices after human consumption by measuring the ability to protect lymphocytes from an oxidative injury and by examining the impact on inflammatory biomarkers in activated THP-1 cells. METHODS: Ten to 12 subjects in each of 13 groups consumed a defined amount of herb or spice for 7 days. Blood was drawn from subjects before consumption and 1 hour after taking the final herb or spice capsules. Subject serum and various extractions of the herbs and spices were analyzed for antioxidant capacity by oxygen radical absorbance capacity (ORAC) analysis or by 1,1-diphenyl-2-picrylhydrzyl (DPPH). Subject peripheral blood mononuclear cells (PBMCs) in medium with10% autologous serum were incubated with hydrogen peroxide to induce DNA strand breaks. Subject serum was also used to treat activated THP-1 cells to determine relative quantities of 3 inflammatory cytokine (tumor necrosis factor-α [TNF-α], interleukin-1α [IL-1α], and IL-6) mRNAs. RESULTS: Herbs and spices that protected PBMCs against DNA strand breaks were paprika, rosemary, ginger, heat-treated turmeric, sage, and cumin. Paprika also appeared to protect cells from normal apoptotic processes. Of the 3 cytokine mRNAs studied (TNF-α, IL-1α, and IL-6), TNF-α was the most sensitive responder to oxidized LDL-treated macrophages. Clove, ginger, rosemary, and turmeric were able to significantly reduce oxidized LDL-induced expression of TNF-α. Serum from those consuming ginger reduced all three inflammatory biomarkers. Ginger, rosemary, and turmeric showed protective capacity by both oxidative protection and inflammation measures. CONCLUSIONS: DNA strand breaks and inflammatory biomarkers are a good functional measure of a food's bioavailability.",
"title": "Bioavailability of herbs and spices in humans as determined by ex vivo inflammatory suppression and DNA strand breaks."
},
{
"docid": "MED-2831",
"text": "TNFs are major mediators of inflammation and inflammation-related diseases, hence, the United States Food and Drug Administration (FDA) has approved the use of blockers of the cytokine, TNF-α, for the treatment of osteoarthritis, inflammatory bowel disease, psoriasis and ankylosis. These drugs include the chimeric TNF antibody (infliximab), humanized TNF-α antibody (Humira) and soluble TNF receptor-II (Enbrel) and are associated with a total cumulative market value of more than $20 billion a year. As well as being expensive ($15 000–20 000 per person per year), these drugs have to be injected and have enough adverse effects to be given a black label warning by the FDA. In the current report, we describe an alternative, curcumin (diferuloylmethane), a component of turmeric (Curcuma longa) that is very inexpensive, orally bioavailable and highly safe in humans, yet can block TNF-α action and production in in vitro models, in animal models and in humans. In addition, we provide evidence for curcumin's activities against all of the diseases for which TNF blockers are currently being used. Mechanisms by which curcumin inhibits the production and the cell signalling pathways activated by this cytokine are also discussed. With health-care costs and safety being major issues today, this golden spice may help provide the solution. Linked Articles This article is part of a themed section on Emerging Therapeutic Aspects in Oncology. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.169.issue-8",
"title": "Curcumin: an orally bioavailable blocker of TNF and other pro-inflammatory biomarkers"
}
] |
[
{
"docid": "MED-4994",
"text": "BACKGROUND: The cardioprotective properties of moderate alcohol consumption, compared with abstinence or heavy drinking, are widely reported, but whether the benefits are experienced equally by all moderate drinkers is less well known. AIMS: To examine the association between average alcohol intake per week and the incidence of fatal and non-fatal myocardial infarction during 17 years of follow-up for 9655 men and women without prevalent disease in the general population; and to test whether the level of cardioprotection differs according to subjects' other health behaviours (healthy, moderately healthy, unhealthy) at entry to the study. METHOD: A longitudinal, British civil service-based cohort study, baseline in 1985-8. RESULTS: A significant benefit of moderate drinking compared with abstinence or heavy drinking was found among those with poor health behaviours (little exercise, poor diet and smokers). No additional benefit from alcohol was found among those with the healthiest behaviour profile (> or =3 hours of vigorous exercise per week, daily fruit or vegetable consumption and non-smokers). CONCLUSION: The cardioprotective benefit from moderate drinking does not apply equally to all drinkers, and this variability should be emphasised in public health messages.",
"title": "Who benefits most from the cardioprotective properties of alcohol consumption--health freaks or couch potatoes?"
},
{
"docid": "MED-1743",
"text": "This article describes the nutrient and elemental composition, including residues of herbicides and pesticides, of 31 soybean batches from Iowa, USA. The soy samples were grouped into three different categories: (i) genetically modified, glyphosate-tolerant soy (GM-soy); (ii) unmodified soy cultivated using a conventional \"chemical\" cultivation regime; and (iii) unmodified soy cultivated using an organic cultivation regime. Organic soybeans showed the healthiest nutritional profile with more sugars, such as glucose, fructose, sucrose and maltose, significantly more total protein, zinc and less fibre than both conventional and GM-soy. Organic soybeans also contained less total saturated fat and total omega-6 fatty acids than both conventional and GM-soy. GM-soy contained high residues of glyphosate and AMPA (mean 3.3 and 5.7 mg/kg, respectively). Conventional and organic soybean batches contained none of these agrochemicals. Using 35 different nutritional and elemental variables to characterise each soy sample, we were able to discriminate GM, conventional and organic soybeans without exception, demonstrating \"substantial non-equivalence\" in compositional characteristics for 'ready-to-market' soybeans. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.",
"title": "Compositional differences in soybeans on the market: glyphosate accumulates in Roundup Ready GM soybeans."
},
{
"docid": "MED-1646",
"text": "The Beverage Guidance Panel was assembled to provide guidance on the relative health and nutritional benefits and risks of various beverage categories. The beverage panel was initiated by the first author. The Panel's purpose is to attempt to systematically review the literature on beverages and health and provide guidance to the consumer. An additional purpose of the Panel is to develop a deeper dialog among the scientific community on overall beverage consumption patterns in the United States and on the great potential to change this pattern as a way to improve health. Over the past several decades, levels of overweight and obesity have increased across all population groups in the United States. Concurrently, an increased daily intake of 150-300 kcal (for different age-sex groups) has occurred, with approximately 50% of the increased calories coming from the consumption of calorically sweetened beverages. The panel ranked beverages from the lowest to the highest value based on caloric and nutrient contents and related health benefits and risks. Drinking water was ranked as the preferred beverage to fulfill daily water needs and was followed in decreasing value by tea and coffee, low-fat (1.5% or 1%) and skim (nonfat) milk and soy beverages, noncalorically sweetened beverages, beverages with some nutritional benefits (fruit and vegetable juices, whole milk, alcohol, and sports drinks), and calorically sweetened, nutrient-poor beverages. The Panel recommends that the consumption of beverages with no or few calories should take precedence over the consumption of beverages with more calories.",
"title": "A new proposed guidance system for beverage consumption in the United States."
},
{
"docid": "MED-1710",
"text": "Sugar intake in the United States has increased by >40 fold since the American Revolution. The health concerns that have been raised about the amounts of sugar that are in the current diet, primarily as beverages, are the subject of this review. Just less than 50% of the added sugars (sugar and high-fructose corn syrup) are found in soft drinks and fruit drinks. The intake of soft drinks has increased 5-fold between 1950 and 2000. Most meta-analyses have shown that the risk of obesity, diabetes, cardiovascular disease, and metabolic syndrome are related to consumption of beverages sweetened with sugar or high-fructose corn syrup. Calorically sweetened beverage intake has also been related to the risk of nonalcoholic fatty liver disease, and, in men, gout. Calorically sweetened beverages contribute to obesity through their caloric load, and the intake of beverages does not produce a corresponding reduction in the intake of other food, suggesting that beverage calories are “add-on” calories. The increase in plasma triglyceride concentrations by sugar-sweetened beverages can be attributed to fructose rather than glucose in sugar. Several randomized trials of sugar-containing soft drinks versus low-calorie or calorie-free beverages show that either sugar, 50% of which is fructose, or fructose alone increases triglycerides, body weight, visceral adipose tissue, muscle fat, and liver fat. Fructose is metabolized primarily in the liver. When it is taken up by the liver, ATP decreases rapidly as the phosphate is transferred to fructose in a form that makes it easy to convert to lipid precursors. Fructose intake enhances lipogenesis and the production of uric acid. By worsening blood lipids, contributing to obesity, diabetes, fatty liver, and gout, fructose in the amounts currently consumed is hazardous to the health of some people.",
"title": "Energy and Fructose From Beverages Sweetened With Sugar or High-Fructose Corn Syrup Pose a Health Risk for Some People"
},
{
"docid": "MED-1858",
"text": "As a hard tissue dental disease, dental erosion has a multifactorial etiology. The majority of dental erosion that originates from extrinsic sources is the result of dietary intake, particularly acidic beverages. Several preventive means have been proposed to minimize the damage to the dentition, including a reduction in the consumption of causative beverages and the adoption of a specific method of drinking, utilizing a straw instead of a cup. This article presents two cases involving the clinical and radiographic features of erosion lesions associated with chronic and excessive intake of acidic carbonated beverages. These examples embody how drinking patterns influence the formation of erosion lesions in various anatomic locations within the dentition. The clinical and radiographic evidence presented in this report cautions against the use of nonspecific terms, such as \"cup versus straw,\" and instead suggests implementing a more precise description of the suggested method. In view of the extensive damage inflicted by the chronic, excessive intake of carbonated beverages, preventive measures are considered to be the only effective course of management. This article offers illustrative examples of erosion lesions associated with long-term excessive intake of carbonated beverages. The influence of the drinking method--that is, a straw positioned into the labial vestibule versus a cup--on the anatomic location of the erosion lesions will be demonstrated through clinical and radiographic evidence.",
"title": "Influence of drinking patterns of carbonated beverages on dental erosion."
},
{
"docid": "MED-713",
"text": "The effect of beverages prepared from the dried calyx of the flowers of Hibiscus sabdariffa on the excretion of diclofenac was investigated using a controlled study in healthy human volunteers. A high pressure liquid chromatographic method was used to analyse the 8 h urine samples collected after the administration of diclofenac with 300 mL (equivalent to 8.18 mg anthocyanins) of the beverage administered daily for 3 days. An unpaired two-tailed t-test was used to analyse for significant difference observed in the amount of diclofenac excreted before and after administration of the beverage. There was a reduction in the amount of diclofenac excreted and the wide variability observed in the control with the water beverage of Hibiscus sabdariffa (p < 0.05). There is an increasing need to counsel patients against the use of plant beverages with drugs.",
"title": "Effects of water extract of Hibiscus sabdariffa, Linn (Malvaceae) 'Roselle' on excretion of a diclofenac formulation."
},
{
"docid": "MED-1627",
"text": "Sweetened beverages, coffee, and tea are the most consumed non-alcoholic beverages and may have important health consequences. We prospectively evaluated the consumption of various types of beverages assessed in 1995–1996 in relation to self-reported depression diagnosis after 2000 among 263,923 participants of the NIH-AARP Diet and Health Study. Odds ratios (OR) and 95% confidence intervals (CI) were derived from multivariate logistic regressions. The OR (95% CI) comparing ≥4 cans/cups per day with none were 1.30 (95%CI: 1.17–1.44) for soft drinks, 1.38 (1.15–1.65) for fruit drinks, and 0.91 (0.84–0.98) for coffee (all P for trend<0.0001). Null associations were observed for iced-tea and hot tea. In stratified analyses by drinkers of primarily diet versus regular beverages, the ORs were 1.31 (1.16–1.47) for diet versus 1.22 (1.03–1.45) for regular soft drinks, 1.51 (1.18–1.92) for diet versus 1.08 (0.79–1.46) for regular fruit drinks, and 1.25 (1.10–1.41) for diet versus 0.94 (0.83–1.08) for regular sweetened iced-tea. Finally, compared to nondrinkers, drinking coffee or tea without any sweetener was associated with a lower risk for depression, adding artificial sweeteners, but not sugar or honey, was associated with higher risks. Frequent consumption of sweetened beverages, especially diet drinks, may increase depression risk among older adults, whereas coffee consumption may lower the risk.",
"title": "Sweetened Beverages, Coffee, and Tea and Depression Risk among Older US Adults"
},
{
"docid": "MED-897",
"text": "The effects of different polyphenol-containing beverages on Fe absorption from a bread meal were estimated in adult human subjects from the erythrocyte incorporation of radio-Fe. The test beverages contained different polyphenol structures and were rich in either phenolic acids (chlorogenic acid in coffee), monomeric flavonoids (herb teas, camomile (Matricaria recutita L.), vervain (Verbena officinalis L.), lime flower (Tilia cordata Mill.), pennyroyal (Mentha pulegium L.) and peppermint (Mentha piperita L.), or complex polyphenol polymerization products (black tea and cocoa). All beverages were potent inhibitors of Fe absorption and reduced absorption in a dose-dependent fashion depending on the content of total polyphenols. Compared with a water control meal, beverages containing 20-50 mg total polyphenols/serving reduced Fe absorption from the bread meal by 50-70%, whereas beverages containing 100-400 mg total polyphenols/serving reduced Fe absorption by 60-90%. Inhibition by black tea was 79-94%, peppermint tea 84%, pennyroyal 73%, cocoa 71%, vervain 59%, lime flower 52% and camomile 47%. At an identical concentration of total polyphenols, black tea was more inhibitory than cocoa, and more inhibitory than herb teas camomile, vervain, lime flower and pennyroyal, but was of equal inhibition to peppermint tea. Adding milk to coffee and tea had little or no influence on their inhibitory nature. Our findings demonstrate that herb teas, as well as black tea, coffee and coca can be potent inhibitors of Fe absorption. This property should be considered when giving dietary advice in relation to Fe nutrition.",
"title": "Inhibition of non-haem iron absorption in man by polyphenolic-containing beverages."
},
{
"docid": "MED-3763",
"text": "The aim of this study was to explore oral exposure to carcinogenic (group 1) acetaldehyde after single sips of strong alcoholic beverages containing no or high concentrations of acetaldehyde. Eight volunteers tasted 5 ml of ethanol diluted to 40 vol.% with no acetaldehyde and 40 vol.% calvados containing 2400 μM acetaldehyde. Salivary acetaldehyde and ethanol concentrations were measured by gas chromatography. The protocol was repeated after ingestion of ethanol (0.5 g/kg body weight). Salivary acetaldehyde concentration was significantly higher after sipping calvados than after sipping ethanol at 30s both with (215 vs. 128 μmol/l, p<0.05) and without (258 vs. 89 μmol/l, p<0.05) alcohol ingestion. From 2 min onwards there were no significant differences in the decreasing salivary acetaldehyde concentration, which remained above the level of carcinogenicity still at 10 min. The systemic alcohol distribution from blood to saliva had no additional effect on salivary acetaldehyde after sipping of the alcoholic beverages. Carcinogenic concentrations of acetaldehyde are produced from ethanol in the oral cavity instantly after a small sip of strong alcoholic beverage, and the exposure continues for at least 10 min. Acetaldehyde present in the beverage has a short-term effect on total acetaldehyde exposure. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "A single sip of a strong alcoholic beverage causes exposure to carcinogenic concentrations of acetaldehyde in the oral cavity."
},
{
"docid": "MED-918",
"text": "Consumption of a large amount of dietary fructose induces gastrointestinal intolerance, and glucose has been known as an enhancer of fructose absorption. Erythritol is a nonglycemic sugar alcohol, and it has been suggested that erythritol is absorbed paracellularly. It was hypothesized that paracellular absorption of erythritol could also enhance paracellular absorption of fructose in healthy adults. This is one of the proposed pathways for how additional glucose enhances the absorption of fructose. Thirty-seven nondiabetic, healthy adults participated in a randomized, double-masked, controlled crossover study. After an overnight fast, participants consumed beverages containing either 50 g fructose and 50 g glucose, 50 g fructose and 33.3 g erythritol (an equimolar concentration of fructose), or 50 g fructose alone. Breath hydrogen response was determined for 8 hours postprandially. Gastrointestinal intolerance symptoms and the number and consistency of bowel movements were recorded for 24 hours postprandially. The breath hydrogen area under the curve (AUC) of the fructose and erythritol beverage was 2 times the AUC of the fructose beverage and 8.75 times the AUC of the fructose and glucose beverage (P < .001, respectively). Compared with fructose and glucose beverage and fructose alone, frequency of watery stools increased (P < .05) and gastrointestinal tolerance worsened (P < .05) when participants consumed fructose and erythritol. These data suggest that coingestion of equimolar concentrations of fructose and erythritol increased carbohydrate malabsorption. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "Combination of erythritol and fructose increases gastrointestinal symptoms in healthy adults."
},
{
"docid": "MED-1637",
"text": "Epidemiologic studies suggest that tea consumption decreases the risk for cardiovascular events. However, there has been no clinical report examining the effects of tea consumption on coronary circulation. The purpose of this study was to evaluate the effects of black tea on coronary flow velocity reserve (CFVR) using transthoracic Doppler echocardiography (TTDE). This was a double-blind crossover study of 10 healthy male volunteers conducted to compare the effects of black tea and caffeine on coronary circulation. The coronary flow velocity of the left anterior descending coronary artery was measured at baseline and at hyperemia during adenosine triphosphate infusion by TTDE to determine CFVR. The CFVR ratio was defined as the ratio of CFVR after beverage consumption to CFVR before beverage consumption. All data were divided into 2 groups according to beverage type: group T (black tea) and group C (caffeine). Two-way analysis of variance showed a significant group effect and interaction in CFVR before and after beverage consumption (p = 0.001). CFVR significantly increased after tea consumption in group T (4.5 +/- 0.9 vs 5.2 +/- 0.9, p <0.0001). The CFVR ratio of group T was larger than that of group C (1.18 +/- 0.07 vs 1.04 +/- 0.08, p = 0.002). Acute black tea consumption improves coronary vessel function, as determined by CFVR.",
"title": "Black tea increases coronary flow velocity reserve in healthy male subjects."
},
{
"docid": "MED-1707",
"text": "Sugar-sweetened drinks have been associated with several health problems. In the point narrative as presented below, we provide our opinion and review of the data to date that we need to reconsider consumption of dietary sugar based on the growing concern of obesity and type 2 diabetes. In the counterpoint narrative following our contribution, Drs. Kahn and Sievenpiper provide a defense and suggest that dietary sugar is not the culprit. Data from the National Health and Nutrition Examination Survey and U.S. Department of Agriculture dietary surveys along with commercial Homescan data on household purchases were used to understand changes in sugar and fructose consumption. Meta-analyses and randomized clinical trials were used to evaluate outcomes of beverage and fructose intake. About 75% of all foods and beverages contain added sugar in a large array of forms. Consumption of soft drinks has increased fivefold since 1950. Meta-analyses suggest that consumption of sugar-sweetened beverages (SSBs) is related to the risk of diabetes, the metabolic syndrome, and cardiovascular disease. Drinking two 16-ounce SSBs per day for 6 months induced features of the metabolic syndrome and fatty liver. Randomized controlled trials in children and adults lasting 6 months to 2 years have shown that lowering the intake of soft drinks reduced weight gain. Recent studies suggest a gene-SSB potential relationship. Consumption of calorie-sweetened beverages has continued to increase and plays a role in the epidemic of obesity, the metabolic syndrome, and fatty liver disease. Reducing intake of soft drinks is associated with less weight gain.",
"title": "Dietary sugar and body weight: have we reached a crisis in the epidemic of obesity and diabetes?: health be damned! Pour on the sugar."
},
{
"docid": "MED-3533",
"text": "This study ascertained whether a proprietary tart cherry juice blend (CherryPharm, Inc., Geneva, NY, USA) associated with anecdotal reports of sleep enhancement improves subjective reports of insomnia compared to a placebo beverage. The pilot study used a randomized, double-blind, crossover design where each participant received both treatment and placebo for 2 weeks with an intervening 2-week washout period. Sleep continuity (sleep onset, wake after sleep onset, total sleep time, and sleep efficiency) was assessed by 2-week mean values from daily sleep diaries and disease severity by the Insomnia Severity Index in a cohort of 15 older adults with chronic insomnia who were otherwise healthy. The tart cherry juice beverage was associated with statistically significant pre- to post-treatment improvements on all sleep variables. When compared to placebo, the study beverage produced significant reductions in insomnia severity (minutes awake after sleep onset); no such improvements were observed for sleep latency, total sleep time, or sleep efficiency compared to placebo. Effect sizes were moderate and in some cases negligible. The results of this pilot study suggest that CherryPharm, a tart cherry juice blend, has modest beneficial effects on sleep in older adults with insomnia with effect sizes equal to or exceeding those observed in studies of valerian and in some, but not all, studies of melatonin, the two most studied natural products for insomnia. These effects, however, were considerably less than those for evidence-based treatments of insomnia: hypnotic agents and cognitive-behavioral therapies for insomnia.",
"title": "Effects of a Tart Cherry Juice Beverage on the Sleep of Older Adults with Insomnia: A Pilot Study"
},
{
"docid": "MED-4822",
"text": "Objective We examined the associations between sweets, sweetened and unsweetened beverages, and sugars and pancreatic cancer risk. Methods We conducted a population-based case–control study (532 cases, 1,701 controls) and used multivariate logistic regression models to calculate odds ratios (OR) and 95% confidence intervals (CI). Because associations were often different by sex, we present results for men and women combined and separately. Results Among men, greater intakes of total and specific sweets were associated with pancreatic cancer risk (total sweets: OR = 1.9, 95% CI: 1.0, 3.6; sweet condiments: OR = 1.9, 95% CI: 1.2, 3.1; chocolate candy: OR = 2.4, 95% CI: 1.1, 5.0; other mixed candy bars: OR = 3.3, 95% CI: 1.5, 7.3 for 1 + servings/day versus none/rarely). Sweets were not consistently associated with risk among women. Sweetened beverages were not associated with increased pancreatic cancer risk. In contrast, low-calorie soft drinks were associated with increased risk among men only; while other low-/non-caloric beverages (e.g., coffee, tea, and water) were unassociated with risk. Of the three sugars assessed (lactose, fructose, and sucrose), only the milk sugar lactose was associated with pancreatic cancer risk (OR = 2.0, 95% CI: 1.5, 2.7 comparing extreme quartiles). Conclusion These results provide limited support for the hypothesis that sweets or sugars increase pancreatic cancer risk.",
"title": "Sweets, sweetened beverages, and risk of pancreatic cancer in a large population-based case–control study"
},
{
"docid": "MED-5046",
"text": "Epidemiological evidence suggests a role for tea catechins in reduction of chronic disease risk. However, stability of catechins under digestive conditions is poorly understood. The objective of this study was to characterize the effect of common food additives on digestive recovery of tea catechins. Green tea water extracts were formulated in beverages providing 4.5, 18, 23, and 3.5 mg per 100 mL epicatechin (EC), epigallocatechin (EGC), epigallocatechin-gallate (EGCG), and epicatechin-gallate (ECG), respectively. Common commercial beverage additives; citric acid (CA), BHT, EDTA, ascorbic acid (AA), milk (bovine, soy, and rice), and citrus juice (orange, grapefruit, lemon, and lime) were formulated into finished tea beverages at incremental dosages. Samples were then subjected to in vitro digestion simulating gastric and small intestinal conditions with pre- and post-digestion catechin profiles assessed by HPLC. Catechin stability in green tea was poor with <20% total catechins remaining post-digestion. EGC and EGCG were most sensitive with less, not double equals 10% recovery. Teas formulated with 50% bovine, soy, and rice milk increased total catechin recovery significantly to 52, 55, and 69% respectively. Including 30 mg AA in 250 mL of tea beverage significantly (p<0.05) increased catechin recovery of EGC, EGCG, EC, and ECG to 74, 54, 82, and 45% respectively. Juice preparation resulted in the highest recovery of any formulation for EGC (81-98%), EGCG (56-76%), EC (86-95%), and ECG (30-55%). These data provide evidence that tea consumption practices and formulation factors likely impact catechin digestive recovery and may result in diverse physiological profiles.",
"title": "Common tea formulations modulate in vitro digestive recovery of green tea catechins."
},
{
"docid": "MED-2219",
"text": "Our laboratory recently reported that a 3-month exposure of rats to cola-like beverages induced sex hormone changes. The aim of the study was to investigate the effects of various types of Coca-cola intake with different composition for 6 months on oxidative status in testes and testosterone in adult male rats. Fifty adult male Wistar rats were divided into control group drinking water, and groups drinking different Coca-cola beverages (regular Coca-cola, Coca-cola caffeine-free, Coca-cola Light and Coca-cola Zero). Oxidative and carbonyl stress markers were measured in the testicular tissue to assess oxidative status together with testicular and plasma testosterone. StAR expression in testes as a marker of steroidogenesis was quantified. No significant differences were found between the groups in any of the measured parameters. In conclusion, oxidative and carbonyl stress in testicular tissue were not influenced by drinking any type of Coca-cola. Additionally, testosterone in testes and in plasma, as well as testicular StAR expression were comparable among the groups. Copyright © 2013 Elsevier Ltd. All rights reserved.",
"title": "No harmful effect of different Coca-cola beverages after 6 months of intake on rat testes."
},
{
"docid": "MED-3375",
"text": "OBJECTIVE: To describe food and beverage types offered and consumed during classroom celebrations at an elementary school in a low-income, urban community. In addition, to report student intake of fresh fruit provided alongside other party foods. METHODS: Observations held during 4 classroom celebrations. Food and beverage items were measured and counted before and after each celebration. Consumption data were recorded in aggregate for the entire classroom and later adjusted to mean intake per student. RESULTS: Majority of items offered were low-nutrient, energy-dense foods. Mean caloric intake during celebrations ranged from 259 to 455 cal. Fruit provided during 2 of the 4 classroom celebrations resulted in a mean intake of 1 full serving per student. CONCLUSIONS AND IMPLICATIONS: Caloric intake from low-nutrient, energy-dense foods and beverages offered during classroom celebrations contributed 20% or more of daily caloric needs. However, fresh fruit may be a reasonable addition to the party food table. Copyright © 2012 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.",
"title": "Classroom \"cupcake\" celebrations: observations of foods offered and consumed."
},
{
"docid": "MED-2461",
"text": "This study aimed to evaluate the association of diet with respiratory symptoms and asthma in schoolchildren in Taipei, Taiwan. An in-class interview survey elicited experiences of asthma and respiratory symptoms and consumption frequencies of the major food categories in 2290 fifth graders. Respiratory symptoms surveyed included persistent cough, chest tightness, wheezing with cold, wheezing without cold, dyspnea-associated wheezing, and exercise-induced cough or wheezing. Results showed that the consumption of sweetened beverages had the strongest association with respiratory symptoms and was positively associated with six of the seven respiratory symptoms (all p < 0.05). The adjusted odds ratios (aOR) ranged from 1.05 (95% confidence interval (CI = 1.01-1.09) for exercise-induced cough to 1.09 (95% CI = 1.03-1.16) for wheezing without cold. Egg consumption was associated with 5 of the 7 respiratory symptoms. Consumptions of seafood, soy products, and fruits were each negatively associated with one of the seven respiratory symptoms (all p < 0.05). Consumption of seafood was negatively associated with physician-diagnosed asthma and consumptions of sweetened beverages and eggs were positively associated with suspected asthma (p < 0.05). In conclusion, the study suggests that diet is associated with the respiratory symptoms in schoolchildren in Taipei. Consumptions of sweetened beverages and eggs are associated with increased risk of respiratory symptoms and asthma whereas consumptions of soy products and fruits are associated with reduced risk of respiratory symptoms.",
"title": "The association of diet with respiratory symptoms and asthma in schoolchildren in Taipei, Taiwan."
},
{
"docid": "MED-4318",
"text": "Preliminary data in the literature indicate that iron absorption from a meal may be increased when consumed with low-pH beverages such as cola, and it is also possible that sugar iron complexes may alter iron availability. A randomized, crossover trial was conducted to compare the bioavailability of nonheme iron from a vegetarian pizza meal when consumed with 3 different beverages (cola, diet cola, and mineral water). Sixteen women with serum ferritin concentrations of 11-54 µg/L were recruited and completed the study. The pizza meal contained native iron and added ferric chloride solution as a stable isotope extrinsic label; the total iron content of the meal was ~5.3 mg. Incorporation of iron from the meal into RBC was not affected by the type of drink (9.9% with cola, 9.4% with diet cola, and 9.6% with water). Serum ferritin and plasma hepcidin were correlated (r = 0.66; P<0.001) and both were significant predictors of iron bioavailability, but their combined effect explained only 30% of the inter-individual variation (P<0.001) and illustrates the current lack of understanding of mechanisms responsible for the fine-tuning of iron absorption. Although there was no effect of low-pH drinks on iron bioavailability in healthy women, their effect on absorption of fortification iron that requires solubilization in dilute acid, such as reduced iron, and in individuals with low gastric acid production, such as older people and individuals with Helicobacter pylori infection, warrants further investigation.",
"title": "Low-pH cola beverages do not affect women's iron absorption from a vegetarian meal."
},
{
"docid": "MED-2226",
"text": "BACKGROUND: Studies of cocoa suggest an array of cardiovascular benefits; however, the effects of daily intake of sugar-free and sugar-sweetened cocoa beverages on endothelial function (EF) have yet to be established. METHODS: 44 adults (BMI 25-35 kg/m2) participated in a randomized, controlled, crossover trial. Participants were randomly assigned to a treatment sequence: sugar-free cocoa beverage, sugar-sweetened cocoa beverage, and sugar-sweetened cocoa-free placebo. Treatments were administered daily for 6 weeks, with a 4-week washout period. RESULTS: Cocoa ingestion improved EF measured as flow-mediated dilation (FMD) compared to placebo (sugar-free cocoa: change, 2.4% [95% CI, 1.5 to 3.2] vs. -0.8% [95% CI, -1.9 to 0.3]; difference, 3.2% [95% CI, 1.8 to 4.6]; p<0.001 and sugar-sweetened cocoa: change, 1.5% [95% CI, 0.6 to 2.4] vs. -0.8% [95% CI, -1.9 to 0.3]; difference, 2.3% [95% CI, 0.9 to 3.7]; p=0.002). The magnitude of improvement in FMD after consumption of sugar-free versus sugar-sweetened cocoa was greater, but not significantly. Other biomarkers of cardiac risk did not change appreciably from baseline. BMI remained stable throughout the study. CONCLUSIONS: Daily cocoa ingestion improves EF independently of other biomarkers of cardiac risk, and does not cause weight gain. Sugar-free preparations may further augment endothelial function. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.",
"title": "Effects of sugar-sweetened and sugar-free cocoa on endothelial function in overweight adults."
},
{
"docid": "MED-2155",
"text": "Coffee, after water, is the most widely consumed beverage in the United States, and is the principal source of caffeine intake among adults. The biological effects of coffee may be substantial and are not limited to the actions of caffeine. Coffee is a complex beverage containing hundreds of biologically active compounds, and the health effects of chronic coffee intake are wide ranging. From a cardiovascular (CV) standpoint, coffee consumption may reduce the risk of type 2 diabetes mellitus and hypertension, as well as other conditions associated with CV risk such as obesity and depression; but it may adversely affect lipid profiles depending on how the beverage is prepared. Regardless, a growing body of data suggests that habitual coffee consumption is neutral to beneficial regarding the risks of a variety of adverse CV outcomes including coronary heart disease, congestive heart failure, arrhythmias, and stroke. Moreover, large epidemiological studies suggest that regular coffee drinkers have reduced risks of mortality, both CV and all-cause. The potential benefits also include protection against neurodegenerative diseases, improved asthma control, and lower risk of select gastrointestinal diseases. A daily intake of ∼2 to 3 cups of coffee appears to be safe and is associated with neutral to beneficial effects for most of the studied health outcomes. However, most of the data on coffee's health effects are based on observational data, with very few randomized, controlled studies, and association does not prove causation. Additionally, the possible advantages of regular coffee consumption have to be weighed against potential risks (which are mostly related to its high caffeine content) including anxiety, insomnia, tremulousness, and palpitations, as well as bone loss and possibly increased risk of fractures. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.",
"title": "Effects of habitual coffee consumption on cardiometabolic disease, cardiovascular health, and all-cause mortality."
},
{
"docid": "MED-4878",
"text": "Background Telomere length reflects biological aging and may be influenced by environmental factors, including those that affect inflammatory processes. Objective With data from 840 white, black, and Hispanic adults from the Multi-Ethnic Study of Atherosclerosis, we studied cross-sectional associations between telomere length and dietary patterns and foods and beverages that were associated with markers of inflammation. Design Leukocyte telomere length was measured by quantitative polymerase chain reaction. Length was calculated as the amount of telomeric DNA (T) divided by the amount of a single-copy control DNA (S) (T/S ratio). Intake of whole grains, fruit and vegetables, low-fat dairy, nuts or seeds, nonfried fish, coffee, refined grains, fried foods, red meat, processed meat, and sugar-sweetened soda were computed with responses to a 120-item food-frequency questionnaire completed at baseline. Scores on 2 previously defined empirical dietary patterns were also computed for each participant. Results After adjustment for age, other demographics, lifestyle factors, and intakes of other foods or beverages, only processed meat intake was associated with telomere length. For every 1 serving/d greater intake of processed meat, the T/S ratio was 0.07 smaller (β ± SE: −0.07 ± 0.03, P = 0.006). Categorical analysis showed that participants consuming ≥1 serving of processed meat each week had 0.017 smaller T/S ratios than did nonconsumers. Other foods or beverages and the 2 dietary patterns were not associated with telomere length. Conclusions Processed meat intake showed an expected inverse association with telomere length, but other diet features did not show their expected associations.",
"title": "Dietary patterns, food groups, and telomere length in the Multi-Ethnic Study of Atherosclerosis (MESA)"
},
{
"docid": "MED-5244",
"text": "Coffee, after water, is the most widely consumed beverage in the United States, and is the principal source of caffeine intake among adults. The biological effects of coffee may be substantial and are not limited to the actions of caffeine. Coffee is a complex beverage containing hundreds of biologically active compounds, and the health effects of chronic coffee intake are wide ranging. From a cardiovascular (CV) standpoint, coffee consumption may reduce the risk of type 2 diabetes mellitus and hypertension, as well as other conditions associated with CV risk such as obesity and depression; but it may adversely affect lipid profiles depending on how the beverage is prepared. Regardless, a growing body of data suggests that habitual coffee consumption is neutral to beneficial regarding the risks of a variety of adverse CV outcomes including coronary heart disease, congestive heart failure, arrhythmias, and stroke. Moreover, large epidemiological studies suggest that regular coffee drinkers have reduced risks of mortality, both CV and all-cause. The potential benefits also include protection against neurodegenerative diseases, improved asthma control, and lower risk of select gastrointestinal diseases. A daily intake of ∼2 to 3 cups of coffee appears to be safe and is associated with neutral to beneficial effects for most of the studied health outcomes. However, most of the data on coffee's health effects are based on observational data, with very few randomized, controlled studies, and association does not prove causation. Additionally, the possible advantages of regular coffee consumption have to be weighed against potential risks (which are mostly related to its high caffeine content) including anxiety, insomnia, tremulousness, and palpitations, as well as bone loss and possibly increased risk of fractures. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.",
"title": "Effects of habitual coffee consumption on cardiometabolic disease, cardiovascular health, and all-cause mortality."
},
{
"docid": "MED-2491",
"text": "Exposure limits for arsenic and lead in drinking water have long been established by the U.S. Environmental Protection Agency and new regulations regarding the presence of these contaminants in bottled water went into effect in California in 2009. No comparable exposure limits or regulations are available, however, for juices and other beverages that may contain arsenic and lead. In the study described in this article, 20 apple juices (or ciders), 15 apple-containing juices, one grape, and one citrus juice were analyzed for arsenic and lead. Arsenic was detected in all juices while lead was detected in more than 94% of juices analyzed. Twelve samples (32%) demonstrated arsenic levels nearly at or above the drinking water exposure limit of 10 parts per billion. No juices contained lead above drinking water exposure limits. Expanding drinking water limits to include juices (and other frequently consumed beverages) would better protect consumers while regular testing of these juices would better inform consumers of the risks posed by specific juices and brands.",
"title": "Arsenic and lead in juice: apple, citrus, and apple-base."
},
{
"docid": "MED-5123",
"text": "The present paper explores the level of evidence required to justify giving dietary advice to the public. There are important practical differences between the development of public health nutrition guidelines and guidelines for clinical practice. While the gold standard for evidence for clinical practice guidelines is a meta-analysis of a number of randomised controlled trials, this is often unrealistic and sometimes unethical for the evaluation of public health nutrition interventions. Hence, epidemiological studies make up the bulk of evidence for nutrition guidelines. Tea and coffee are an interesting case study in relation to this issue. They are two of the most commonly consumed beverages worldwide, yet there is little dietary advice on their use. The evidence for a relationship between coffee or tea consumption and several diseases is discussed. The available studies, predominantly epidemiological, together with animal and in vitro studies, indicate that coffee and tea are both safe beverages. However, tea is the healthier option because it has a possible role in the prevention of several cancers and CVD. While the evidence for such relationships is not strong, the public will continue to drink both tea and coffee, and will continue to ask nutritionists to make recommendations. It is therefore argued that advice should be given on the best available data, as waiting for complete data to become available could have severe consequences for public health.",
"title": "Tea or coffee? A case study on evidence for dietary advice."
},
{
"docid": "MED-1621",
"text": "Except for conflicting evidence about coffee and risk of coronary disease, coffee and tea are not linked to major causes of death. Because of widespread use of both beverages and limitations of prior studies, concern persists. Using Cox models (ten covariates) we studied relations in 128,934 persons to 4501 subsequent deaths. Except for slightly increased risk from acute myocardial infarction among heavier (> or = 4 cups/d) coffee users (relative risk versus nondrinkers = 1.4, 95% confidence interval = 1.0 to 1.9, P = 0.07), there was no increased risk of mortality for all deaths (relative risk per cup of coffee per day = 0.99, 95% confidence interval = 0.97 to 1.01; relative risk per cup of tea per day = 0.98, 95% confidence interval = 0.96 to 1.00) or major causes in adjusted analyses. Coffee was related to lower risk of liver cirrhosis death (relative risk per cup of coffee per day = 0.77, 95% confidence interval = 0.67 to 0.89). Use of both beverages was related to a lower risk of suicide, progressively lower at higher coffee intake (relative risk per cup of coffee per day = 0.87, 95% confidence interval = 0.77 to 0.98). We conclude that coffee and tea have no overall relation to mortality risk. If coffee increases coronary risk, this is balanced by an unexplained lower risk of other conditions, notably cirrhosis and suicide.",
"title": "Coffee, tea, and mortality."
},
{
"docid": "MED-2677",
"text": "Population differences in age-related diseases and cancer could stem from differences in diet. To characterize DNA strand-breaking activities in selected foods/beverages, flavorings, and some of their constituent chemicals, we used p53R cells, a cellular assay sensitive to such breaks. Substances testing positive included reference chemicals: quinacrine (peak response, 51X) and etoposide (33X); flavonoids: EGCG (19X), curcumin (12X), apigenin (9X), and quercetin (7X); beverages: chamomile (11X), green (21X), and black tea (26X) and coffee (3 to 29X); and liquid smoke (4 to 28X). Damage occurred at dietary concentrations: etoposide near 5 μg/ml produced responses similar to a 1:1000 dilution of liquid smoke, a 1:20 dilution of coffee, and a 1:5 dilution of tea. Pyrogallol-related chemicals and tannins are present in dietary sources and individually produced strong activity: pyrogallol (30X), 3-methoxycatechol (25X), gallic acid (21X), and 1,2,4-benzenetriol (21X). From structure-activity relationships, high activities depended on specific orientations of hydroxyls on the benzene ring. Responses accompanied cellular signals characteristic of DNA breaks such as H2AX phosphorylation. Breaks were also directly detected by comet assay. Cellular toxicological effects of foods and flavorings could guide epidemiologic and experimental studies of potential disease risks from DNA strand-breaking chemicals in diets.",
"title": "Biological Clues to Potent DNA-Damaging Activities in Food and Flavoring"
},
{
"docid": "MED-3588",
"text": "Background Many studies have examined whether caffeine, alcohol, or specific beverages containing these affect fertility in women. However most of these studies have retrospectively collected information on alcohol and caffeine intake, making the results susceptible to biases. Methods We followed 18,555 married women without a history of infertility for 8 years as they attempted to become (or became) pregnant. Diet was measured twice during this period and prospectively related to the incidence of ovulatory disorder infertility. Results There were 438 incident report of ovulatory disorder infertility during follow-up. Intakes of alcohol and caffeine were unrelated to the risk of ovulatory disorder infertility. The multivariate-adjusted relative risk (RR), 95% confidence interval (CI), P for trend comparing the highest to lowest categories of intake were 1.11 (0.76–1.64; 0.78) for alcohol and 0.86 (0.61–1.20; 0.44) for total caffeine. However, intake of caffeinated soft drinks was positively related to ovulatory disorder infertility. The multivariate-adjusted RR 95% CI, and P for trend comparing the highest to lowest categories of caffeinated soft drink consumption were 1.47 (1.09–1.98; 0.01). Similar associations were observed for noncaffeinated, sugared, diet and total soft drinks. Conclusions Our findings do not support the hypothesis that alcohol and caffeine impair ovulation to the point of decreasing fertility. The association between soft drinks and ovulatory disorder infertility appears not to be attributable to their caffeine or sugar content, and deserves further investigation.",
"title": "Caffeinated and alcoholic beverage intake in relation to ovulatory disorder infertility"
},
{
"docid": "MED-1185",
"text": "Endogenous sulfite is generated as a consequence of the body's normal processing of sulfur-containing amino acids. Sulfites occur as a consequence of fermentation and also occur naturally in a number of foods and beverages. As food additives, sulfiting agents were first used in 1664 and approved in the United States as long ago as the 1800s. With such long experience with their use, it is easy to understand why these substances have been regarded as safe. They are currently used for a variety of preservative properties, including controlling microbial growth, preventing browning and spoilage, and bleaching some foods. It is estimated that up to 500,000 (< .05% of the population) sulfite-sensitive individuals live in the United States. Sulfite sensitivity occurs most often in asthmatic adults--predominantly women; it is uncommonly reported in preschool children. Adverse reactions to sulfites in nonasthmatics are extremely rare. Asthmatics who are steroid-dependent or who have a higher degree of airway hyperreactivity may be at greater risk of experiencing a reaction to sulfite-containing foods. Even within this limited population, sulfite sensitivity reactions vary widely, ranging from no reaction to severe. The majority of reactions are mild. These manifestations may include dermatologic, respiratory, or gastrointestinal signs and symptoms. Severe nonspecific signs and symptoms occur less commonly. Broncho-constriction is the most common sensitivity response in asthmatics. The precise mechanisms of the sensitivity responses have not been completely elucidated. Inhalation of sulfur dioxide (SO2) generated in the stomach following ingestion of sulfite-containing foods or beverages, a deficiency in a mitochondrial enzyme, and an IgE-mediated immune response have all been implicated.(ABSTRACT TRUNCATED AT 250 WORDS)",
"title": "Sulfite sensitivity: significance in human health."
},
{
"docid": "MED-1640",
"text": "Coffee is one of the most widely used pharmacologically active beverages. The present study was designed to evaluate the acute effect of coffee ingestion on endothelial function in healthy individuals, and the potential role of caffeine. We studied 17 healthy young adults (28.9+/-3.0 years old; nine men), who were regular non-heavy coffee drinkers. The endothelial performance was estimated by endothelium-dependent FMD (flow-mediated dilatation) of the brachial artery before and 30, 60, 90 and 120 min after ingestion of a cup of caffeinated coffee (80 mg of caffeine) or the corresponding decaffeinated beverage (< 2 mg of caffeine) in two separate sessions, following a randomized single-blind cross-over design. There was no difference in baseline FMD values between the two sessions [7.78 compared with 7.07% after caffeinated and decaffeinated coffee respectively; P = NS (not significant)]. Caffeinated coffee led to a decline of FMD (7.78, 2.86, 2.12, 4.44 and 4.57% at baseline, 30, 60, 90 and 120 min respectively; P < 0.001). This adverse effect was focused at 30 (P = 0.004) and 60 min (P < 0.001). No significant effect on FMD was found with the decaffeinated coffee session (7.07, 6.24, 5.21, 7.41 and 5.20%; P = NS). The composite effect of the type of coffee consumed over time on FMD was significantly different (P = 0.021). In conclusion, coffee exerts an acute unfavourable effect on the endothelial function in healthy adults, lasting for at least 1 h after intake. This effect might be attributed to caffeine, given that decaffeinated coffee was not associated with any change in the endothelial performance.",
"title": "Effect of coffee on endothelial function in healthy subjects: the role of caffeine."
}
] |
5a88b2a55542994846c1cebe
|
Carol Thurston starred in eight episodes of "The Life and Legend of Wyatt Earp" and also in which 1953 film directed by Spencer G. Bennet?
|
[
{
"docid": "40512719",
"text": "Killer Ape (1953) is the twelfth Jungle Jim film produced by Columbia Pictures. It features Johnny Weissmuller in his twelfth performance as the protagonist adventurer Jungle Jim. Carol Thurston also stars. The film was directed by Spencer G. Bennet and written by Arthur Hoerl and Carroll Young.",
"title": ""
},
{
"docid": "30110136",
"text": "Carol Thurston (September 27, 1920 – December 31, 1969) was an American film and television actress who played the fictitious Emma Clanton in eight episodes (1959-1961) of the ABC/Desilu western television series, \"The Life and Legend of Wyatt Earp\", starring Hugh O'Brian as frontier peace officer Wyatt Earp.",
"title": ""
}
] |
[
{
"docid": "42773781",
"text": "Jimmy Noel (May 15, 1903–January 31, 1985) was a Massachusetts-born actor and stuntman who appeared in hundreds of largely uncredited roles in film and television between 1949 and 1975. He appeared 202 times on CBS's western series, \"Gunsmoke\", starring James Arness, and in 144 episodes of the ABC/Desilu production, \"The Life and Legend of Wyatt Earp\", with Hugh O'Brian in the title role of deputy Marshal Wyatt Earp. Buddy Roosevelt made similar appearances in sixty-five \"Wyatt Earp\" episodes.",
"title": ""
},
{
"docid": "16537645",
"text": "Frederick Hazlitt Brennan (September 23, 1901 – June 30, 1962) was an American screenwriter of more than thirty films between 1929 and 1953 and the director of the ABC/Desilu western television series, \"The Life and Legend of Wyatt Earp\" (1955-1961), starring Hugh O'Brian as deputy Marshal Wyatt Earp.",
"title": ""
},
{
"docid": "1998796",
"text": "The Life and Legend of Wyatt Earp is the first western television series written for adults, premiering four days before \"Gunsmoke\" on September 6, 1955. It is loosely based on the life of frontier marshal Wyatt Earp. The half-hour black-and-white program aired for 6 seasons (229 episodes) on ABC from 1955 to 1961 and featured Hugh O'Brian in the title role.",
"title": ""
},
{
"docid": "36406131",
"text": "Wyatt Earp: Return to Tombstone is a 1994 independent film starring Hugh O'Brian as Wyatt Earp, featuring new footage mixed with colorized sequences from O'Brian's 1955-1961 television series \"The Life and Legend of Wyatt Earp\". The supporting cast for the new footage includes Bruce Boxleitner, Paul Brinegar, Harry Carey, Jr., Bo Hopkins, and Don Meredith. The colorized flashback archival footage from the original television series features Douglas Fowley as Doc Holliday and Lloyd Corrigan as Ned Buntline. The movie was directed by Paul Landres and Frank McDonald.",
"title": ""
},
{
"docid": "42543113",
"text": "Raymond C. Boyle, known as Ray Boyle or as the screen name Dirk London (born June 28, 1925), is an American actor known principally for his sporadic role as Morgan Earp, the brother of Wyatt Earp in fifteen episodes of the ABC/Desilu Productions western television series, \"The Life and Legend of Wyatt Earp,\" starring Hugh O'Brian in the title role. Boyle's episodes began with \"The Assassins\" in 1956 and ended with \"The Outlaws Cry Murder\" in 1961.",
"title": ""
},
{
"docid": "23440679",
"text": "Carol Montgomery Stone (February 1, 1915 – June 10, 2011) was an actress who played \"Big Nose Kate\", or Kate Holliday, the common law wife of Doc Holliday, in ten episodes in the 1957-1958 season of the ABC/Desilu western television series, \"The Life and Legend of Wyatt Earp\".",
"title": ""
},
{
"docid": "39941754",
"text": "Mason Alan Dinehart (born April 30, 1936), also known as Mason Alan Dinehart III, Alan Dinehart III, or Mase Dinehart, is an American businessman and former actor best known for his role as a youthful Bat Masterson in thirty-four episodes between 1955 and 1959 of the ABC/Desilu television series \"The Life and Legend of Wyatt Earp\", starring Hugh O'Brian in the title role of the frontier marshal Wyatt Earp.",
"title": ""
},
{
"docid": "42767819",
"text": "Americo Zorilla \"Rico\" Alaniz (October 25, 1919 – March 9, 2015) was a Mexican-born American actor in film and television best known for his role of the peaceful Cheyenne informer \"Mr. Cousin\" in sixteen episodes from 1955 to 1959 of the ABC/Desilu western television series, \"The Life and Legend of Wyatt Earp\", with Hugh O'Brian in the title role as deputy Marshal Wyatt Earp.",
"title": ""
},
{
"docid": "2233445",
"text": "Trevor Bardette (November 19, 1902 – November 28, 1977) was an American film and television actor. He appeared in several memorable episodes of \"Adventures of Superman\" and as Newman Haynes Clanton, or Old Man Clanton, in 21 episodes of the ABC/Desilu western series, \"The Life and Legend of Wyatt Earp.\"",
"title": ""
},
{
"docid": "42694161",
"text": "William Tannen (November 17, 1911 – December 2, 1976) was an American actor originally from New York City, who was best known for his role of Deputy Hal Norton in fifty-six episodes from 1956 to 1958 of the ABC/Desilu western television series, \"The Life and Legend of Wyatt Earp\", with Hugh O'Brian as Deputy Marshal Wyatt Earp.",
"title": ""
},
{
"docid": "3039544",
"text": "Wyatt Earp is a 1994 American semi-biographical Western film directed by Lawrence Kasdan and co-written by Kasdan and Dan Gordon. It stars Kevin Costner in the title role as lawman Wyatt Earp, and features an ensemble cast that includes Gene Hackman, Mark Harmon, Michael Madsen, Bill Pullman, Dennis Quaid, Isabella Rossellini, Tom Sizemore, JoBeth Williams, and Mare Winningham.",
"title": ""
},
{
"docid": "40501707",
"text": "Voodoo Tiger (1952) is the ninth Jungle Jim film produced by Columbia Pictures. It features Johnny Weissmuller in his ninth performance as the protagonist adventurer Jungle Jim, and James Seay as the film's antagonist. Jean Byron also stars. The film was directed by Spencer G. Bennet and written by Samuel Newman.",
"title": ""
},
{
"docid": "32035024",
"text": "Wyatt Earp's Revenge is a 2012 American Western film about the legendary lawman Wyatt Earp. It is a fictionalized account of an actual Old West event, the slaying of beautiful singer Dora Hand in Dodge City, Kansas, when Earp was a deputy there. In one of its many instances of dramatic license, the movie depicts Hand as Earp's sweetheart. The film's framing device is a reporter's interview with an aging Earp, who reminisces about the tragedy. (Val Kilmer plays the older Earp, while Shawn Roberts plays the younger one.) The film was released on March 6, 2012, in the United States. The film was produced by Jeff Schenck and Barry Barnholtz and directed by Michael Feifer. The screenplay was written by Darren Benjamin Shepherd.",
"title": ""
},
{
"docid": "643710",
"text": "Michael Søren Madsen (born September 25, 1958) is an American actor, producer, director, writer, poet and photographer. He has starred in over 200 films, including \"Thelma & Louise\", \"Reservoir Dogs\", \"Wyatt Earp\", \"Free Willy\", \"Species\", \"Donnie Brasco\", \"Sin City\", \"Kill Bill\", \"The Hateful Eight\" and many direct-to-video films. He has also guest starred in numerous television series and has done voice work in several video games. Madsen is known for making many films with Quentin Tarantino.",
"title": ""
},
{
"docid": "9426146",
"text": "Frontier Marshal is a 1939 western film directed by Allan Dwan and starring Randolph Scott as Wyatt Earp. The movie is the second film produced by Sol M. Wurtzel based on Stuart N. Lake's biography of Earp, \"\" (later found to be largely fictionalized). An earlier version was Wurtzel's \"Frontier Marshal\", filmed in 1934. A later version of the story was filmed by John Ford in 1946, \"My Darling Clementine\", which included whole scenes reshot from the 1939 film.",
"title": ""
},
{
"docid": "6592954",
"text": "Celia Ann \"Mattie\" Blaylock (January 1850 – July 3, 1888) was a prostitute who became the romantic companion and common-law wife of Old West lawman and gambler Wyatt Earp for about eight years. Knowledge of her place in Wyatt's life was concealed by Josephine Earp, his later common-law wife, who worked hard to protect her and Wyatt's reputation in their later years.",
"title": ""
},
{
"docid": "40389243",
"text": "Devil Goddess (1955) is the sixteenth and final Jungle Jim film produced by Columbia Pictures. It features Johnny Weissmuller in his third and last performance as the protagonist adventurer Johnny Weissmuller (a character previously called \"Jungle Jim\") and Ed Hinton and William Tannen as the film's antagonists, Leopold and Nels Comstock, respectively. Angela Stevens also stars. The film was directed by Spencer G. Bennet and written by Dwight Babcock and George H. Plympton.",
"title": ""
},
{
"docid": "2160135",
"text": "Tombstone: The Town Too Tough to Die is a 1942 Western film directed by William McGann and starring Richard Dix as Wyatt Earp, Kent Taylor as Doc Holliday and Edgar Buchanan as Curly Bill Brocious. The supporting cast of this movie about the gunfight at the OK Corral also features Rex Bell as Virgil Earp and Victor Jory as Ike Clanton.",
"title": ""
},
{
"docid": "47983208",
"text": "Jewels of Brandenburg is a 1947 American crime film directed by Eugene Forde and written by Irving Cummings Jr. and Robert G. North. The film stars Richard Travis, Micheline Cheirel, Leonard Strong, Carol Thurston, Lewis Russell and Louis Mercier. The film was released on May 27, 1947, by 20th Century Fox.",
"title": ""
},
{
"docid": "6592405",
"text": "Warren Baxter Earp (March 9, 1855 – July 6, 1900) was the youngest brother of Wyatt, Morgan, Virgil, James, and Newton Earp. Although he was not present during the Gunfight at the O.K. Corral, after Virgil was maimed in an ambush, Warren joined Wyatt and was in town when Morgan was assassinated. He also helped Wyatt in the hunt for the outlaws they believed responsible. Later in life, Warren developed a reputation as a bully and was killed in an argument in 1900.",
"title": ""
},
{
"docid": "4052442",
"text": "Sunset is a 1988 American mystery action film written and directed by Blake Edwards and starring Bruce Willis as legendary Western actor Tom Mix, who teams up with legendary lawman Wyatt Earp, portrayed for the second time in a theatrical film by James Garner. Based on an unpublished novel by Rod Amateau, the plot has Mix and Earp team up to solve a murder in Hollywood in 1929.",
"title": ""
},
{
"docid": "1483025",
"text": "Gunfight at the O.K. Corral is a 1957 American western film starring Burt Lancaster as Wyatt Earp and Kirk Douglas as Doc Holliday, based on a real event which took place on October 26, 1881. The picture was directed by John Sturges from a screenplay written by novelist Leon Uris.",
"title": ""
},
{
"docid": "47278547",
"text": "Riders of the Frontier, also known as Ridin' the Frontier, is a 1939 American western film directed by Spencer Gordon Bennet and starring Tex Ritter and Jack Rutherford. It is a remake of the 1936 film \"The Cattle Thief\".",
"title": ""
},
{
"docid": "44172999",
"text": "Shark River is a 1953 American Florida Western adventure film directed by John Rawlins and written by Louis Lantz and Lewis Meltzer. It stars Steve Cochran, Carole Mathews, Warren Stevens, Robert Cunningham, Ruth Foreman, Spencer Fox and Bill Piper, and was released on November 13, 1953, by United Artists.",
"title": ""
},
{
"docid": "1558601",
"text": "Hugh O'Brian (born Hugh Charles Krampe; April 19, 1925 – September 5, 2016) was an American actor and humanitarian, best known for his starring roles in the ABC western television series \"The Life and Legend of Wyatt Earp\" (1955–1961) and the NBC action television series \"Search\" (1972–1973), as well as films including the Agatha Christie adaptation \"Ten Little Indians\" (1965); he also had a notable supporting role in John Wayne's last film, \"The Shootist\" (1976). He was highly regarded for creating the Hugh O'Brian Youth Leadership Foundation, a non-profit youth leadership development program for high school scholars which has sponsored over 400,000 students since he founded the program in 1958 following an extended visit with Nobel Peace Prize-winning theologian and physician Albert Schweitzer.",
"title": ""
},
{
"docid": "5455247",
"text": "Hour of the Gun is a 1967 Western film depicting Wyatt Earp and Doc Holliday during their 1881 battles against Ike Clanton and his brothers in the Gunfight at the O.K. Corral, and the gunfight's aftermath in and around Tombstone, Arizona, starring James Garner as Earp, Jason Robards as Holliday, and Robert Ryan as Clanton. The movie was directed by John Sturges.",
"title": ""
},
{
"docid": "31925499",
"text": "The 1976 book I Married Wyatt Earp was believed to be a memoir of his widow Josephine Earp, but was many years later described as a fraud, creative exercise, and a hoax. Originally published by the respected University of Arizona Press, it is the second best-selling book about western Deputy U.S. Marshal Wyatt Earp ever sold. It was regarded for many years as a factual account that shed considerable light on the life of Wyatt Earp and his brothers in Tombstone, Arizona Territory. It was cited in scholarly works, assigned as classroom work, and used as a source by filmmakers. Amateur Earp historian Glenn Boyer said that the retouched image on the cover of a scantily-clad woman was of Josephine in her 20s, and based on his statements, copies of the image were later sold at auction for up to $2,875.",
"title": ""
},
{
"docid": "11192988",
"text": "Paul Brinegar (December 19, 1917 – March 27, 1995) was an American character actor best known for his roles in three western series: \"The Life and Legend of Wyatt Earp\", \"Rawhide\", and \"Lancer\".",
"title": ""
},
{
"docid": "38578122",
"text": "Glenn G. Boyer (January 5, 1924 - February 14, 2013) was a controversial author who published three books and a number of articles about Wyatt Earp and related figures in the American Old West. He was the first person to reveal the existence of Wyatt Earp's second wife, Mattie Blaylock. His publications were for many years regarded as the authoritative source on Wyatt Earp's life. However, when other experts began to seek evidence supporting Boyer's work, he would or could not prove the existence of documents that he said he owned and had cited as essential sources. In one case, an individual he cited as a key source was exposed as a complete fabrication. His reputation and the authenticity of his work was seriously damaged. Although he retained many supporters, his work became surrounded by controversy.",
"title": ""
},
{
"docid": "3214830",
"text": "John Maxwell (March 11, 1918 Spokane, Washington – July 18, 1982) was an American film and television actor who appeared in over 100 films of the 1940s and 1950s. Many times the actor appeared in films uncredited. Occasionally he played larger roles in movies, such as in \"The Prowler\". He was born in Spokane, Washington. His television guest appearances included \"The Lone Ranger\", \"Lassie\", \"The Life and Legend of Wyatt Earp\", \"The Rifleman\" and \"Bonanza\".",
"title": ""
}
] |
PLAIN-2203
|
Taiwan
|
[
{
"docid": "MED-1959",
"text": "Since 1991 the US Department of Agriculture (USDA) has conducted annual surveys of pesticide residues in foods under the Agricultural Marketing Service's Pesticide Data Program (PDP). To assess chemical residues in domestically marketed catfish products, 1479 catfish samples were collected during the 2008-2010 PDPs. A subset of 202 samples was analysed for 17 toxic polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs). The average pattern of the individual PCDD/F congener concentrations in the catfish was rather unique in that it had almost no measurable amounts of polychlorinated dibenzofurans (PCDFs), but all PCDDs were present. This pattern was more dominant in the domestically produced catfish products than in the imported products (China/Taiwan). Comparison of the pattern to known sources of PCDD/Fs showed strong similarities to the pattern of PCDD/Fs found in kaolin clays which have often been used as anti-caking agents in animal feeds. To investigate whether catfish feeds may be the source of the PCDD/Fs found in the catfish, archived catfish feed data from a US Food and Drug Administration (USFDA) database were examined. In 61 out of 112 feed samples, the PCDD concentrations were 50 times higher than the PCDF concentrations and resembled the pattern found in the catfish products and in clays mined in the south-eastern United States. Although the source of PCDD/Fs in domestically marketed catfish products cannot be definitively established, mined clay products used in feeds should be considered a likely source and, given the wide concentration range of PCDD/Fs that has been found in clays, a critical control point for PCDD/Fs entrance to the food supply.",
"title": "Dioxin congener patterns in commercial catfish from the United States and the indication of mineral clays as the potential source."
},
{
"docid": "MED-2179",
"text": "OBJECTIVE: To investigate the association between cooking behaviour and long-term survival among elderly Taiwanese. DESIGN: Cohort study. The duration of follow-up was the interval between the date of interview and the date of death or 31 December 2008, when censored for survivors. Information used included demographics, socio-economic status, health behaviours, cooking frequencies, physical function, cognitive function, nutrition knowledge awareness, eating out habits and food and nutrient intakes. These data were linked to death records. Cox proportional-hazards models were used to evaluate cooking frequency on death from 1999 to 2008 with related covariate adjustments. SETTING: Elderly Nutrition and Health Survey in Taiwan, 1999-2000. SUBJECTS: Nationally representative free-living elderly people aged ≥65 years (n 1888). RESULTS: During a 10-year follow-up, 695 participants died. Those who cooked most frequently were younger, women, unmarried, less educated, non-drinkers of alcohol, non-smokers, without chewing difficulty, had spouse as dinner companion, normal cognition, who walked or shopped more than twice weekly, who ate less meat and more vegetables. Highly frequent cooking (>5 times/week, compared with never) predicted survival (hazard ratio (HR) = 0·47; 95 % CI, 0·36, 0·61); with adjustment for physical function, cognitive function, nutrition knowledge awareness and other covariates, HR was 0·59 (95 % CI, 0·41, 0·86). Women benefited more from cooking more frequently than did men, with decreased HR, 51 % v. 24 %, when most was compared with least. A 2-year delay in the assessment of survivorship led to similar findings. CONCLUSIONS: Cooking behaviour favourably predicts survivorship. Highly frequent cooking may favour women more than men.",
"title": "Cooking frequency may enhance survival in Taiwanese elderly."
},
{
"docid": "MED-2311",
"text": "BACKGROUND: The association between fruit and vegetable (FV) consumption and overall mortality has seldom been investigated in large cohort studies. Findings from the few available studies are inconsistent. OBJECTIVE: The objective was to examine the dose-response relation between FV consumption and mortality, in terms of both time and rate, in a large prospective cohort of Swedish men and women. DESIGN: FV consumption was assessed through a self-administrated questionnaire in a population-based cohort of 71,706 participants (38,221 men and 33,485 women) aged 45-83 y. We performed a dose-response analysis to evaluate 10th survival percentile differences (PDs) by using Laplace regression and estimated HRs by using Cox regression. RESULTS: During 13 y of follow-up, 11,439 deaths (6803 men and 4636 women) occurred in the cohort. In comparison with 5 servings FV/d, a lower consumption was progressively associated with shorter survival and higher mortality rates. Those who never consumed FV lived 3 y shorter (PD: -37 mo; 95% CI: -58, -16 mo) and had a 53% higher mortality rate (HR: 1.53; 95% CI: 1.19, 1.99) than did those who consumed 5 servings FV/d. Consideration of fruit and vegetables separately showed that those who never consumed fruit lived 19 mo shorter (PD: -19 mo; 95% CI: -29, -10 mo) than did those who ate 1 fruit/d. Participants who consumed 3 vegetables/d lived 32 mo longer than did those who never consumed vegetables (PD: 32 mo; 96% CI: 13, 51 mo). CONCLUSION: FV consumption <5 servings/d is associated with progressively shorter survival and higher mortality rates. The Swedish Mammography Cohort and the Cohort of Swedish Men were registered at clinicaltrials.gov as NCT01127698 and NCT01127711, respectively.",
"title": "Fruit and vegetable consumption and all-cause mortality: a dose-response analysis."
},
{
"docid": "MED-1958",
"text": "Food, especially meat, milk, and fish, is the immediate source of almost all polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and dioxinlike compounds in the general population. To estimate intake of these highly toxic compounds, we performed congener-specific dioxin analyses for the first time on U.S. food for 18 dairy meat, and fish samples from a supermarket in upstate New York. 2,3,7,8 Tetrachlorodibenzo-p-dioxin (TCDD, \"dioxin\") toxic equivalents (TEqs) on a wet weight basis for the dairy products ranged for 0.04 to 0.7 ppt, meat TEqs ranged from 0.03 to 1.5 ppt, and fish TEqs ranged from 0.02 to 0.13 ppt. Previous human breast milk and infant formula analyses were used with the current preliminary food data to estimate a range of dioxin intake for Americans. Average daily food intake of TEqs for an adult weighing 65 kg was estimated to be between 0.3 and 3.0 pg/kg body weight, for a total of 18-192 pg TEq, using 1986 American consumption rates. Due to the relatively high level of PCDDs and PCDFs commonly found in human breast milk from American women and from women in other industrial countries, a nursing infant may consume an average of 35-53 pg TEq/kg body weight/day in its first year of life. This may be compared with the current U.S. EPA virtually safe dose of 0.006 pg TCDD/kg body weight per day over a 70-year lifetime based on an upper limit cancer risk of 10(-6), or the 10 pg/kg/day used by some European government agencies.",
"title": "Congener-specific levels of dioxins and dibenzofurans in U.S. food and estimated daily dioxin toxic equivalent intake."
},
{
"docid": "MED-1963",
"text": "In 1994, we analyzed 43 foodstuff samples from local supermarkets in southern Mississippi, USA, for PCDD/PCDF. 2,3,7,8-Cl4DD could be quantified in 31 of these samples. On a lipid basis, levels in meat (0.53-1.10 pg I-TEQ/g) and dairy products (0.42-1.10 pg I-TEQ/g) were slightly lower than those reported from other industrialized countries. While levels in dairy samples from the United States and Europe are comparable, there is a difference in the contribution of individual congeners to the I-TEQ: for example, in milk samples from Germany approximately 40% of the I-TEQ is due to the presence of 2,3, 4,7,8-Cl5DF while in the Mississippi samples this congener only contributes 16%. The highest concentrations of PCDD/PCDF in our study were detected in the farm-raised catfish (10.2-27.8 pg I-TEQ/g). A unique finding was that in addition to the 2,3,7,8-substituted PCDD/PCDF the catfish samples contained many non-2,3,7,8-substituted congeners. This is unusual because vertebrate animals selectively eliminate or metabolize the non-2,3,7,8-substituted congeners.",
"title": "Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/PCDF) in food samples collected in southern Mississippi, USA."
},
{
"docid": "MED-1962",
"text": "The concentrations of the 2,3,7,8-Cl substituted dibenzo-p-dioxins/-furans (PCDDs/PCDFs) were determined in the edible tissues of whole chicken fryers and compared with the values found in their abdominal fat. The values are presented both on a whole weight basis and on a lipid adjusted basis for each tissue. While there is a marked difference in the concentration of the 2,3,7,8-dibenzo-p-dioxins in the edible tissues expressed on a whole weight basis, the lipid-adjusted concentrations of the individual dioxins were not statistically different in the various tissues. This validates the use of lipid adjusted concentrations of 2,3,7,8-PCDDs/PCDFs in abdominal fat for the determination of the presence of these compounds in different tissues.",
"title": "The concentration and distribution of 2,3,7,8-dibenzo-p-dioxins/-furans in chickens."
},
{
"docid": "MED-2182",
"text": "Over the past century, a major shift in North American food practices has been taking place. However, the literature on this topic is lacking in several areas. Some available research on food and cooking practices in the current context is presented, with a focus on how these are affecting health and how they might be contributing to health inequalities within the population. First, cooking and cooking skills are examined, along with the ambiguities related to terms associated with cooking in the research literature. Food choice, cooking, and health are described, particularly in relation to economic factors that may lead to health inequalities within the population. The importance of developing an understanding of factors within the wider food system as part of food choice and cooking skills is presented, and gaps in the research literature are examined and areas for future research are presented. Cooking practices are not well studied but are important to an understanding of human nutritional health as it relates to cultural, environmental, and economic factors.",
"title": "Food, cooking skills, and health: a literature review."
},
{
"docid": "MED-1957",
"text": "One combined catfish feed sample from Arkansas, USA, and its eight ingredients were analyzed for PCDDs and PCDFs. One of the ingredients, soybean meal, was highly contaminated by PCDDs, especially the toxic 2,3,7,8-substituted congeners, e.g., 7.3 pg/g dry weight or 370 pg/g lipid for the 2,3,7,8-tetra CDD. The I-TEQ value for the soybean meal was 11.4 pg/g dry weight or 576 pg/g fat. The corresponding values for the combined catfish feed concentrations were approximately 3 times lower. The congener pattern, the congener profile and the ratio sigma PCDDs/sigma PCDFs for the soybean meal were quite unique. We are not aware of any environmental sample or technical product with similar characteristics. As a result, natural formation of the PCDDs found in the soybean meal cannot be ruled out.",
"title": "PCDD and PCDF contamination in catfish feed from Arkansas, USA."
},
{
"docid": "MED-2310",
"text": "OBJECTIVES To examine the relationship between fruit and vegetable intake, physical activity, and all-cause mortality in older women. DESIGN Six Cox proportional hazards models examined independent and additive relationships between physical activity, carotenoids, and all-cause mortality. Additional models tested whether physical activity and carotenoids were conjointly related to mortality. Models were adjusted for age, education, and race and ethnicity. SETTING Baltimore, Maryland. PARTICIPANTS Seven hundred thirteen women aged 70 to 79 participating in the Women’s Health and Aging Studies. MEASUREMENTS Total serum carotenoids, a marker of fruit and vegetable intake, and physical activity were measured at baseline. Physical activity was measured according to kilocalorie expenditure. RESULTS During 5 years of follow-up, 82 (11.5%) participants died. Measured continuously, physical activity improved survival (HR = 0.52, 95% CI = 0.41–0.66, P < .001). The most active women were more likely to survive than the least physically active women (HR = 0.28, 95% CI = 0.13–0.59, P < .001). Continuous measures of carotenoids improved survival (HR = 0.67, 95% CI = 0.51–0.89, P = .01). Women in the highest tertile of total carotenoids were more likely to survive those in the lowest (HR = 0.50, 95% CI = 0.27–0.91, P = .03). When examined in the same model, continuous measures of physical activity (HR = 0.54, 95% CI = 0.42–0.68, P < .001) and carotenoids (HR = 0.76, 95% CI = 0.59–0.98, P = .04) predicted survival during follow-up. CONCLUSION The combination of low total serum carotenoids and low physical activity, both modifiable risk factors, strongly predicted earlier mortality. These findings provide preliminary support that higher fruit and vegetable intake and exercise improve survival.",
"title": "Fruit and Vegetable Intake, Physical Activity, and Mortality in Older Community-Dwelling Women"
},
{
"docid": "MED-1961",
"text": "Dioxins and related compounds are undesirable and unintended contaminants in the food supply, and dietary intake is the major route of exposure. Reducing dietary exposure to dioxins among the most vulnerable segments of the population (i.e., pregnant women, infants, and young girls) is an effective strategy for reducing body burdens in future generations. Exposure to dioxins through foods can be minimized by selecting lower-fat versions of meats, poultry, and dairy products. Consuming all foods, including fatty fish, in recommended amounts is congruent with the goal of reducing dioxin intake exposure and maintaining good health.",
"title": "Reducing exposure to dioxins and related compounds through foods in the next generation."
},
{
"docid": "MED-1541",
"text": "We propose the hypothesis that a vegetarian diet reduces the risk of developing diabetes. Findings that have generated this hypothesis are from a population of 25,698 adult White Seventh-day Adventists identified in 1960. During 21 years of follow-up, the risk of diabetes as an underlying cause of death in Adventists was approximately one-half the risk for all US Whites. Within the male Adventist population, vegetarians had a substantially lower risk than non-vegetarians of diabetes as an underlying or contributing cause of death. Within both the male and female Adventist populations, the prevalence of self-reported diabetes also was lower in vegetarians than in non-vegetarians. The associations observed between diabetes and meat consumption were apparently not due to confounding by over- or under-weight, other selected dietary factors, or physical activity. All of the associations between meat consumption and diabetes were stronger in males than in females.",
"title": "Does a vegetarian diet reduce the occurrence of diabetes?"
},
{
"docid": "MED-2181",
"text": "Background Little is known about the impact of location of food consumption and preparation upon daily energy intake for children. Objective To examine trends in daily energy intake by children for foods eaten at home or away-from-home, by source of preparation, and for combined categories of eating location and food source. Subjects The analysis uses data from 29,217 children aged 2–18 years from the 1977–1978 Nationwide Food Consumption Survey, 1989–1991 and 1994–1998 Continuing Survey of Food Intake by Individuals, and 2003–2006 National Health and Nutrition Examination Surveys. Methods Nationally representative weighted percentages and means of daily energy intake by eating location were analyzed for trends from 1977 to 2006. Comparisons by food source were examined from 1994 to 2006. Analyses were repeated for 3 age groups: 2–6, 7–12, and 13–18 year olds. Difference testing was conducted using a t test. Results Increased energy intake (+179 kcal/d) by children from 1977–2006 was associated with a major increase in calories eaten away-from-home (+255 kcal/d). The percentage of kcal/d eaten away-from-home increased from 23.4% to 33.9% from 1977–2006. No further increase was observed from 1994–2006, but the sources of calories shifted. The percentage of calories from fast food increased to surpass intake from schools and become the largest contributor to foods prepared away-from-home for all age groups. For foods eaten away-from-home, the percentage of kcal/d from stores increased to become the largest source of calories eaten away-from-home. Fast food eaten at home and store-bought food eaten away-from-home increased significantly. Conclusion Eating location and food source significantly impact daily energy intake for children. Foods prepared away-from-home, including fast food eaten at home and store-prepared food eaten away-from-home, are fueling the increase in total calorie intake. However, further research using alternative data sources is necessary to verify that store-bought foods eaten away-from-home are increasingly store-prepared.",
"title": "Trends in energy intake among US children by eating location and food source, 1977–2006"
},
{
"docid": "MED-2180",
"text": "Objectives To compare the energy and macronutrient content of main meals created by television chefs with ready meals sold by supermarkets, and to compare both with nutritional guidelines published by the World Health Organization and UK Food Standards Agency. Design Cross sectional study. Setting Three supermarkets with the largest share of the grocery market in the United Kingdom, 2010. Samples 100 main meal recipes from five bestselling cookery books by UK television chefs and 100 own brand ready meals from the three leading UK supermarkets. Main outcome measures Number of meals for which the nutritional content complied with WHO recommendations, and the proportion of nutrients classified as red, amber, or green using the UK FSA’s “traffic light” system for labelling food. Results No recipe or ready meal fully complied with the WHO recommendations. The ready meals were more likely to comply with the recommended proportions of energy derived from carbohydrate (18% v 6%, P=0.01) and sugars (83% v 81%, P=0.05) and fibre density (56% v 14% P<0.01). The recipes were more likely to comply with the recommended sodium density (36% v 4%, P<0.01), although salt used for seasoning was not assessed. The distributions of traffic light colours under the FSA’s food labelling recommendations differed: the modal traffic light was red for the recipes (47%) and green for ready meals (42%). Overall, the recipes contained significantly more energy (2530 kJ v 2067 kJ), protein (37.5 g v 27.9 g), fat (27.1 g v 17.2 g), and saturated fat (9.2 g v 6.8 g; P<0.01 for all) and significantly less fibre (3.3 g v 6.5 g, P<0.01) per portion than the ready meals. Conclusions Neither recipes created by television chefs nor ready meals sold by three of the leading UK supermarkets complied with WHO recommendations. Recipes were less healthy than ready meals, containing significantly more energy, protein, fat, and saturated fat, and less fibre per portion than the ready meals.",
"title": "Christmas 2012: Research: Nutritional content of supermarket ready meals and recipes by television chefs in the United Kingdom: cross sectional study"
},
{
"docid": "MED-2308",
"text": "Background Few studies have evaluated the linkage between food cost and mortality among older adults. This study considers the hypothesis that greater food expenditure in general, and particularly on more nutritious plant and animal-derived foods, decreases mortality in older adults. Methods This study uses the 1999–2000 Elderly Nutrition and Health Survey in Taiwan and follows the cohort until 2008, collecting 24-hr dietary recall data for 1781 participants (874 men and 907 women) aged 65 y or older. Using monthly mean national food prices and 24-hr recall, this study presents an estimate of daily expenditures for vegetable, fruit, animal-derived, and grain food categories. Participants were linked to the national death registry. Results Of the 1781 original participants, 625 died during the 10-y follow-up period. Among the 4 food categories, the fourth and fifth expenditure quintiles for vegetables and for fruits had the highest survival rates. After adjusting for co-variates, higher (Q4) vegetable and higher fruit (Q4) food expenditures referent to Q1 were significantly predictive of reduced mortality (HR = 0.55, 95% CI: 0.39-0.78 and HR = 0.64, 95% CI: 0.42–0.99, respectively) and the risk decreased by 12% and 10% for every NT$15 (US$0.50) increase in their daily expenditures. Animal-derived and grain food spending was not predictive of mortality. Conclusion Greater and more achievable vegetable and fruit affordability may improve food security and longevity for older adults.",
"title": "Spending on vegetable and fruit consumption could reduce all-cause mortality among older adults"
},
{
"docid": "MED-1960",
"text": "Nine catfish fillets, three catfish nuggets, two feed samples, and one pond sediment were analyzed for PCDD, PCDF, and PCB. Farm-raised catfish from Mississippi, Alabama, and Arkansas contained significant levels of 2,3,7,8-substituted PCDD and PCDF. In addition, a large number of non-2,3,7,8-substituted congeners were present in all samples. The catfish fillets and catfish nuggets also contained high concentrations of dioxin-like PCB, as well as a number of non-dioxin-like PCB. The TEQ based on PCDD and PCDF ranged from 9.5 to 43.0 pg/g lipid and the TEQ based on PCB ranged from 0.45 to 4.9 pg/g lipid for all catfish samples. The dioxin-like PCB contributed 4-16% to the total TEQ (PCDD/PCDF/PCB) for the catfish samples. The major source for the PCDD, PCDF, and PCB appears to be from feed and not from pond sediment. Immunoreactive CYP1A protein was elevated 2.5 fold in the pond-raised catfish compared to the aquarium-raised one. The results of this study suggest that the PCDD/PCDF are more important than the PCB in the CYP1A induction.",
"title": "PCDD, PCDF, and PCB in farm-raised catfish from southeast United States--concentrations, sources, and CYP1A induction."
},
{
"docid": "MED-1540",
"text": "A number of studies have evaluated the health of vegetarians. Others have studied the health effects of foods that are preferred or avoided by vegetarians. The purpose of this review is to look critically at the evidence on the health effects of vegetarian diets and to seek possible explanations where results appear to conflict. There is convincing evidence that vegetarians have lower rates of coronary heart disease, largely explained by low LDL cholesterol, probable lower rates of hypertension and diabetes mellitus, and lower prevalence of obesity. Overall, their cancer rates appear to be moderately lower than others living in the same communities, and life expectancy appears to be greater. However, results for specific cancers are much less convincing and require more study. There is evidence that risk of colorectal cancer is lower in vegetarians and in those who eat less meat; however, results from British vegetarians presently disagree, and this needs explanation. It is probable that using the label “vegetarian” as a dietary category is too broad and that our understanding will be served well by dividing vegetarians into more descriptive subtypes. Although vegetarian diets are healthful and are associated with lower risk of several chronic diseases, different types of vegetarians may not experience the same effects on health.",
"title": "Vegetarian diets: what do we know of their effects on common chronic diseases?"
},
{
"docid": "MED-1956",
"text": "The U.S. Food and Drug Administration (FDA) terminated the use of ball clay from a mine in Mississippi as an additive in animal feed after discovering nanogram per gram concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD). The FDA collected chicken eggs and farm-raised catfish in affected areas and throughout the remaining continental United States to assess levels of 2,3,7,8-TCDD. A new method using quadrupole ion storage tandem-in-time mass spectrometry (QISTMS) measured the 2,3,7,8-TCDD levels in 42 catfish fillet composites, 3 Tilapia fillet composites, 46 chicken egg samples, and 6 chicken feeds. Six catfish composites and 20 egg samples had 2,3,7,8-TCDD concentrations significantly above 1.0 pg/g wet weight of fillet or whole egg. Farm-raised catfish not exposed to feed containing ball clay had a mean 2,3,7,8-TCDD concentration of 0.12 pg/g. The TCDD isomer pattern in ball clay differed from the TCDD isomer pattern in a fly ash sample and from the \"chick edema factor\" TCDD pattern in a sample of reference toxic fat used as a feed ingredient in the 1950s.",
"title": "Elevated TCDD in chicken eggs and farm-raised catfish fed a diet with ball clay from a Southern United States mine."
},
{
"docid": "MED-2183",
"text": "Objective Cooking programs are growing in popularity; however an extensive review has not examined overall impact. Therefore, this study reviewed previous research on cooking/home food preparation interventions and diet and health-related outcomes among adults and identified implications for practice and research. Design Literature review and descriptive summative method. Main outcome measures Dietary intake, knowledge/skills, cooking attitudes and self-efficacy/confidence, health outcomes. Analysis Articles evaluating effectiveness of interventions that included cooking/home food preparation as the primary aim (January 1980 through December 2011) were identified via OVID MEDLINE, Agricola and Web of Science databases. Studies grouped according to design and outcomes were reviewed for validity using an established coding system. Results were summarized for several outcome categories. Results Of 28 studies identified, 12 included a control group with six as non-randomized and six as randomized controlled trials. Evaluation was done post-intervention for five studies, pre- and post-intervention for 23 and beyond post-intervention for 15. Qualitative and quantitative measures suggested a positive influence on main outcomes. However, non-rigorous study designs, varying study populations, and use of non-validated assessment tools limited stronger conclusions. Conclusions and Implications Well-designed studies are needed that rigorously evaluate long-term impact on cooking behavior, dietary intake, obesity and other health outcomes.",
"title": "Impact of cooking and home food preparation interventions among adults: outcomes and implications for future programs"
},
{
"docid": "MED-2184",
"text": "Objectives. We examined the effects of state-level unemployment rates during the recession of 2008 on patterns of home food preparation and away-from-home (AFH) eating among low-income and minority populations. Methods. We analyzed pooled cross-sectional data on 118 635 adults aged 18 years or older who took part in the American Time Use Study. Multinomial logistic regression models stratified by gender were used to evaluate the associations between state-level unemployment, poverty, race/ethnicity, and time spent cooking, and log binomial regression was used to assess respondents’ AFH consumption patterns. Results. High state-level unemployment was associated with only trivial increases in respondents’ cooking patterns and virtually no change in their AFH eating patterns. Low-income and racial/ethnic minority groups were not disproportionately affected by the recession. Conclusions. Even during a major economic downturn, US adults are resistant to food-related behavior change. More work is needed to understand whether this reluctance to change is attributable to time limits, lack of knowledge or skill related to food preparation, or lack of access to fresh produce and raw ingredients.",
"title": "Resistant to the Recession: Low-Income Adults’ Maintenance of Cooking and Away-From-Home Eating Behaviors During Times of Economic Turbulence"
},
{
"docid": "MED-2309",
"text": "BACKGROUND: Similar to the general population in Taiwan, the health of aborigines has steadily improved over the last 30 years, but the gap remains wide, especially in males, despite an infusion of substantial medical resources. The objectives of this study are to quantify the contribution of major causes of death to the gap in life expectancy and to propose initiatives to bridge the health gap between aborigines and the general population. METHODS: This study included residents (slightly over 200000) from 30 'aboriginal townships' in Taiwan. The gap in life expectancy between aborigines and the general population was analysed by decomposing these gaps according to major causes of deaths. This analysis quantifies the contribution of different causes of deaths to the gap in life expectancy between the two populations. RESULTS: The overall mortality of aborigines in these townships was approximately 70% higher than the respective male and female general populations over the past 30 years. Mortality from infectious disease, cirrhosis of the liver, accidents, and suicide are substantially higher than the general population. The gap in life expectancy at birth in males was 8.5 years during 1971-1973, increasing to 13.5 years by 1998-2000, however, the gap in females remained relatively stable (8.0 years and 8.4 years, respectively). Of the 13.5-year difference in life expectancy in males, the differential mortality from diseases of the digestive system (mainly due to cirrhosis of the liver), accidents (from both motor vehicle and non-motor vehicle accidents), and infectious and parasitic disease contributed half (50%) of the gap in life expectancy. In females, the above primarily preventable causes of deaths accounted for 41% of the life expectancy gap. CONCLUSIONS: Based on the findings of this study, we suggest that future focus should be in the area of primary prevention in order to reduce the incidence of infectious and parasitic diseases, liver cirrhosis, and accidents.",
"title": "Bridging the gap in life expectancy of the aborigines in Taiwan."
}
] |
[
{
"docid": "MED-3378",
"text": "BACKGROUND AND OBJECTIVE: In 1981, a Petrol-Lead Phase-Out Program (PLPOP) was launched in Taiwan for the abatement of environmental lead emissions. The present study was intended to examine whether the high Petrol-Lead Emission Areas (PLEA) would result in an increase in the incidence rate of brain cancer based on a national data bank. METHODS: The national brain cancer incidence data was obtained from the Taiwan National Cancer Registry. Age standardized incidence rates were calculated based on the 2000 WHO world standard population, and gasoline consumption data was obtained from the Bureau of Energy. The differences in the trend tests for age-standardized incidence rates of brain cancer between high, median, low, and small PLEA were analyzed. RESULTS: A significant increase was found from small to high PLEA in age-standardized incidence rates of brain cancer. By taking six possible confounders into account, the age-standardized incidence rates for brain cancer were highly correlated with the median and high PLEA by reference to the small PLEA. CONCLUSION: After being adjusted for a number of relevant confounders, it could be concluded that high PLEA might result in an increase in the incidence rate of brain cancer resulting from high lead exposures. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Brain cancer associated with environmental lead exposure: evidence from implementation of a National Petrol-Lead Phase-Out Program (PLPOP) in Taiwa..."
},
{
"docid": "MED-2461",
"text": "This study aimed to evaluate the association of diet with respiratory symptoms and asthma in schoolchildren in Taipei, Taiwan. An in-class interview survey elicited experiences of asthma and respiratory symptoms and consumption frequencies of the major food categories in 2290 fifth graders. Respiratory symptoms surveyed included persistent cough, chest tightness, wheezing with cold, wheezing without cold, dyspnea-associated wheezing, and exercise-induced cough or wheezing. Results showed that the consumption of sweetened beverages had the strongest association with respiratory symptoms and was positively associated with six of the seven respiratory symptoms (all p < 0.05). The adjusted odds ratios (aOR) ranged from 1.05 (95% confidence interval (CI = 1.01-1.09) for exercise-induced cough to 1.09 (95% CI = 1.03-1.16) for wheezing without cold. Egg consumption was associated with 5 of the 7 respiratory symptoms. Consumptions of seafood, soy products, and fruits were each negatively associated with one of the seven respiratory symptoms (all p < 0.05). Consumption of seafood was negatively associated with physician-diagnosed asthma and consumptions of sweetened beverages and eggs were positively associated with suspected asthma (p < 0.05). In conclusion, the study suggests that diet is associated with the respiratory symptoms in schoolchildren in Taipei. Consumptions of sweetened beverages and eggs are associated with increased risk of respiratory symptoms and asthma whereas consumptions of soy products and fruits are associated with reduced risk of respiratory symptoms.",
"title": "The association of diet with respiratory symptoms and asthma in schoolchildren in Taipei, Taiwan."
},
{
"docid": "MED-118",
"text": "The aims of this study were to determine the concentrations of 4-nonylphenol (NP) and 4-octylphenol (OP) in 59 human milk samples and to examine related factors including mothers' demographics and dietary habits. Women who consumed over the median amount of cooking oil had significantly higher OP concentrations (0.98 ng/g) than those who consumed less (0.39 ng/g) (P < 0.05). OP concentration was significantly associated with the consumption of cooking oil (beta = 0.62, P < 0.01) and fish oil capsules (beta = 0.39, P < 0.01) after adjustment for age and body mass index (BMI). NP concentration was also significantly associated with the consumption of fish oil capsules (beta = 0.38, P < 0.01) and processed fish products (beta = 0.59, P < 0.01). The food pattern of cooking oil and processed meat products from factor analysis was strongly associated with OP concentration in human milk (P < 0.05). These determinations should aid in suggesting foods for consumption by nursing mothers in order to protect their infants from NP/OP exposure. 2010 Elsevier Ltd. All rights reserved.",
"title": "Alkylphenols in human milk and their relations to dietary habits in central Taiwan."
},
{
"docid": "MED-2651",
"text": "The aims of this study were to determine the concentrations of 4-nonylphenol (NP) and 4-octylphenol (OP) in 59 human milk samples and to examine related factors including mothers' demographics and dietary habits. Women who consumed over the median amount of cooking oil had significantly higher OP concentrations (0.98 ng/g) than those who consumed less (0.39 ng/g) (P < 0.05). OP concentration was significantly associated with the consumption of cooking oil (beta = 0.62, P < 0.01) and fish oil capsules (beta = 0.39, P < 0.01) after adjustment for age and body mass index (BMI). NP concentration was also significantly associated with the consumption of fish oil capsules (beta = 0.38, P < 0.01) and processed fish products (beta = 0.59, P < 0.01). The food pattern of cooking oil and processed meat products from factor analysis was strongly associated with OP concentration in human milk (P < 0.05). These determinations should aid in suggesting foods for consumption by nursing mothers in order to protect their infants from NP/OP exposure. 2010 Elsevier Ltd. All rights reserved.",
"title": "Alkylphenols in human milk and their relations to dietary habits in central Taiwan."
},
{
"docid": "MED-1613",
"text": "The present study was designed to examine the effects of habitual consumption of Taiwanese vegetarian diets on hormonal secretion, and on lipid and glycaemic control. Of the ninety-eight healthy female adults recruited from Hualien, Taiwan (aged 31-45 years), forty-nine were Buddhist lactovegetarians and forty-nine were omnivores. Dietary intakes were measured, and blood levels of nutrients and hormones were analysed. Vegetarians consumed less energy, fat and protein, but more fibre than the omnivores. Compared with the omnivores, the vegetarians had, on average, lower BMI and smaller waist circumference. Except for slightly lower levels of thyroxine (T4) in vegetarians, vegetarians and omnivores both showed similar levels of triiodothyronine (T3), free T4, thyroid-stimulating hormone, T3:T4 ratio and cortisol. Compared with the omnivores, the vegetarians had significantly lower levels of fasting insulin (median: 35.3 v. 50.6 pmol/l) and plasma glucose (mean: 4.7 (se 0.05) v. 4.9 (se 0.05) mmol/l). Insulin resistance, as calculated by the homeostasis model assessment method, was significantly lower in the vegetarians than in the omnivores (median: 1.10 v. 1.56), while beta-cell function was not different between the two groups. BMI and diet were both independent predictors for insulin resistance, and contributed 18 and 15 % of the variation in insulin resistance, respectively. In conclusion, Taiwanese vegetarians had lower glucose and insulin levels and higher insulin sensitivity than did the omnivores. Diet and lower BMI were partially responsible for the high insulin sensitivity observed in young Taiwanese vegetarians.",
"title": "Taiwanese vegetarians have higher insulin sensitivity than omnivores."
},
{
"docid": "MED-3947",
"text": "Hibiscus sabdariffa Linne (Malvaceae), an attractive plant believed to be native to Africa, is cultivated in the Sudan and Eastern Taiwan. Anthocyanins exist widely in many vegetables and fruits. Some reports demonstrated that anthocyanins extracted from H. sabdariffa L., Hibiscus anthocyanins (HAs) (which are a group of natural pigments existing in the dried calyx of H. sabdariffa L.) exhibited antioxidant activity and liver protection. Therefore, in this study, we explored the effect of HAs on human cancer cells. The result showed that HAs could cause cancer cell apoptosis, especially in HL-60 cells. Using flow cytometry, we found that HAs treatment (0-4 mg/ml) markedly induced apoptosis in HL-60 cells in a dose- and time-dependent manner. The result also revealed increased phosphorylation in p38 and c-Jun, cytochrome c release, and expression of tBid, Fas, and FasL in the HAs-treated HL-60 cells. We further used SB203580 (p38 inhibitor), PD98059 (MEK inhibitor), SP600125 (JNK inhibitor), and wortmannin (phosphatidylinositol 3-kinase; PI-3K inhibitor) to evaluate their effect on the HAs-induced HL-60 death. The data showed that only SB203580 had strong potential in inhibiting HL-60 cell apoptosis and related protein expression and phosphorylation. Therefore, we suggested that HAs mediated HL-60 apoptosis via the p38-FasL and Bid pathway. According to these results, HAs could be developed as chemopreventive agents. However, further investigations into the specificity and mechanism(s) of HAs are needed.",
"title": "Hibiscus anthocyanins rich extract-induced apoptotic cell death in human promyelocytic leukemia cells."
},
{
"docid": "MED-3681",
"text": "OBJECTIVE: To determine the effects of the probiotic lactic acid bacterium, Lactobacillus rhamnosus HN001, on natural cellular immunity when delivered orally in normal low-fat milk (LFM) or lactose-hydrolyzed low-fat milk (LFM-LH). DESIGN: A three stage, pre-post intervention trial, spanning nine weeks. SETTING: Taipei Medical College Hospital, Taipei, Taiwan. SUBJECTS: Fifty-two healthy middle-aged and elderly volunteers (17 males, 35 females; median age 63.5, range 44-80). INTERVENTIONS: Stage 1 (run-in diet): 25 g/200 mL reconstituted LFM powder, twice daily for 3 weeks. Stage 2 (probiotic intervention): LFM or LFM-LH, supplemented with 10(9) CFUs/g L. rhamnosus HN001 in each case, for 3 weeks. Stage 3 (wash-out): LFM for 3 weeks. MEASURES OF OUTCOME: In vitro phagocytic capacity of peripheral blood polymorphonuclear (PMN) leukocytes; in vitro tumoricidal activity of natural killer (NK) leukocytes. RESULTS: Immunological responses were unaffected by the run-in diet of LFM alone. In contrast, the relative proportion of PMN cells showing phagocytic activity increased by 19% and 15%, respectively, following consumption of HN001 in either LFM or LFM-LH; the relative level of NK cell tumor killing activity increased by 71% and 147%. In most cases these levels declined following cessation, but remained above baseline. CONCLUSIONS: Dietary consumption of L. rhamnosus HN001, in a base of low-fat milk or lactose-hydrolyzed low-fat milk, appears to enhance systemic cellular immune responses and may be useful as a dietary supplement to boost natural immunity.",
"title": "Systemic immunity-enhancing effects in healthy subjects following dietary consumption of the lactic acid bacterium Lactobacillus rhamnosus HN001."
},
{
"docid": "MED-4832",
"text": "Cardiovascular disease (CVD) is the most important adult health problem in the world. Epidemiological studies and laboratory experiments have shown that fruit and vegetable consumption has protective effects against CVD. The purpose of the study was to investigate the effects of consumption of two kiwifruit per day on the lipid profile, antioxidants and markers of lipid peroxidation in hyperlipidemic adult men and women in Taiwan. Forty-three subjects who had hyperlipidemia, including 13 males and 30 females, participated in this study. They were asked to consume two kiwifruit per day for 8 weeks. Anthropometric measurements were made. Before the intervention and at 4 and 8 weeks of the intervention, fasting blood samples were analyzed for total cholesterol, triacylglycerol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein cholesterol (HDL-C). Additionally vitamin E and vitamin C, the malondialdehyde + 4-hydroxy-2(E)-nonenal concentration, and the lag time of LDL oxidation were determined. No significant differences from baseline to 8 weeks of the intervention were detected for triacylglycerol, total cholesterol, or LDL cholesterol. However, after 8 weeks of consumption of kiwifruit, the HDL-C concentration was significantly increased and the LDL cholesterol/HDL-C ratio and total cholesterol/HDL-C ratio were significantly decreased. Vitamin C and vitamin E also increased significantly. In addition, the lag time of LDL oxidation and malondialdehyde + 4-hydroxy-2(E)-nonenal had significantly changed at 4 and 8 weeks during the kiwifruit intervention. Regular consumption of kiwifruit might exert beneficial effects on the antioxidative status and the risk factors for CVD in hyperlipidemic subjects.",
"title": "Effects of kiwifruit consumption on serum lipid profiles and antioxidative status in hyperlipidemic subjects."
},
{
"docid": "MED-4093",
"text": "OBJECTIVE: The association between hyperuricemia and cardiovascular events has been documented in high-risk groups, but is still undetermined in general populations, especially Chinese. This study assessed the temporal association between serum uric acid level, hyperuricemia, and cardiovascular mortality. METHODS: A prospective cohort study of 41,879 men and 48,514 women ages > or = 35 years was conducted using data from the MJ Health Screening Centers in Taiwan. Mortality from all causes, total cardiovascular disease (CVD), ischemic stroke, congestive heart failure, hypertensive disease, and coronary heart disease were compared according to increasing serum uric acid levels. RESULTS: A total of 1,151 (21.2%) events of 5,427 total deaths were ascribed to CVD (mean followup 8.2 years). Hazard ratios (HRs) for hyperuricemia (serum uric acid level >7 mg/dl) were estimated with Cox regression model after adjusting for age, sex, body mass index, cholesterol, triglycerides, diabetes, hypertension, heavy cigarette smoking, and frequent alcohol consumption. In all patients, HRs were 1.16 (P < 0.001) for all-cause mortality, 1.39 (P < 0.001) for total CVD, and 1.35 (P = 0.02) for ischemic stroke. In subgroup analysis, the HRs for cardiovascular risk remained significant in patients with hypertension (1.44, P < 0.001) and in patients with diabetes (1.64, P < 0.001). In addition, in a low metabolic risk subgroup, the HRs for all-cause mortality and total cardiovascular morbidity were 1.24 (P = 0.02) and 1.48 (P = 0.16), respectively. CONCLUSION: Hyperuricemia was an independent risk factor of mortality from all causes, total CVD, and ischemic stroke in the Taiwanese general population, in high-risk groups, and potentially in low-risk groups.",
"title": "Serum uric acid level as an independent risk factor for all-cause, cardiovascular, and ischemic stroke mortality: a Chinese cohort study."
},
{
"docid": "MED-3435",
"text": "INTRODUCTION: Previous cross-sectional studies have suggested that erectile dysfunction (ED) represents an independent risk factor for future cardiovascular events. However, very few studies have attempted to examine the association between ED and subsequent stroke. AIM: The aim of this study is to estimate the risk of stroke during a 5-year follow-up period after the first ambulatory care visit for the treatment of ED using nationwide, population-based data and a retrospective case-control cohort design in Taiwan. METHODS: This study used data sourced from the \"Longitudinal Health Insurance Database.\" The study cohort comprised 1,501 patients who received a principal diagnosis of ED between 1997 and 2001 and 7,505 randomly selected subjects as the comparison cohort. Each patient (N = 9,006) was then individually tracked for 5 years from their index ambulatory care visit to identify those who had diagnosed episodes of stroke. MAIN OUTCOME MEASURE: Stratified Cox proportional hazard regressions were performed as a means of comparing the 5-year stroke-free survival rate for the two cohorts. RESULTS: Of the sampled patients, 918 (10.2%) developed stroke within the 5-year follow-up period, that is, 188 individuals (12.5% of the patients with ED) from the study cohort and 730 individuals (9.7% of patients in the comparison cohort) from the comparison cohort. The log-rank test indicated that patients with ED had significantly lower 5-year stroke-free survival rates than those in the comparison cohort (P < 0.001). After adjusting for the patient's monthly income, geographical location, hypertension, diabetes, coronary heart disease, peripheral vascular disease, atrial fibrillation, and hyperlipidemia, patients with ED were more likely to have a stroke during the 5-year follow-up period than patients in the comparison cohort (hazard ratio = 1.29, 95% confidence interval = 1.08 - 1.54, P < 0.01). CONCLUSIONS: These results suggest that ED is a surrogate marker for future stroke in men. © 2010 International Society for Sexual Medicine.",
"title": "Increased risk of stroke among men with erectile dysfunction: a nationwide population-based study."
},
{
"docid": "MED-931",
"text": "This study evaluated the toxicological sensitivity of non-feeding larval stages of a key Antarctic species (Antarctic krill, Euphausia superba) to p,p'-dichlorodiphenyl dichloroethylene (p,p'-DDE) exposure. The aqueous uptake clearance rate of 84 mL g(-1) preserved weight (p.w.) h(-1) determined for p,p'-DDE in Antarctic krill larvae is comparable to previous findings for small cold water crustaceans and five times slower than the rates reported for an amphipod inhabiting warmer waters. Natural variations in larval physiology appear to influence contaminant uptake and larval krill behavioural responses, strongly highlighting the importance of time of measurement for ecotoxicological testing. Sublethal narcosis (immobility) was observed in larval Antarctic krill from p,p'-DDE body residues of 0.2 mmol/kg p.w., which is in agreement with findings for adult krill and temperate aquatic species. The finding of comparable body residue-based toxicity of p,p'-DDE between polar and temperate species supports the tissue residue approach for environmental risk assessment of polar ecosystems. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Aqueous uptake and sublethal toxicity of p,p'-DDE in non-feeding larval stages of Antarctic krill (Euphausia superba)."
},
{
"docid": "MED-3371",
"text": "Background: The overconsumption of energy-dense foods leads to excessive energy intakes. The substitution of low-energy-dense vegetables for foods higher in energy density can help decrease energy intakes but may be difficult to implement if individuals dislike the taste of vegetables. Objective: We investigated whether incorporating puréed vegetables to decrease the energy density of entrées at multiple meals reduced daily energy intakes and increased daily vegetable intakes. Design: In this crossover study, 20 men and 21 women ate ad libitum breakfast, lunch, and dinner in the laboratory once a week for 3 wk. Across conditions, entrées at meals varied in energy density from standard versions (100% condition) to reduced versions (85% and 75% conditions) by the covert incorporation of 3 or 4.5 times the amount of puréed vegetables. Entrées were accompanied by unmanipulated side dishes. Participants rated their hunger and fullness before and after meals. Results: Subjects consumed a consistent weight of foods across conditions of energy density; thus, the daily energy intake significantly decreased by 202 ± 60 kcal in the 85% condition (P < 0.001) and by 357 ± 47 kcal in the 75% condition (P < 0.0001). Daily vegetable consumption significantly increased from 270 ± 17 g of vegetables in the 100% condition to 487 ± 25 g of vegetables in the 75% condition (P < 0.0001). Despite the decreased energy intake, ratings of hunger and fullness did not significantly differ across conditions. Entrées were rated as similar in palatability across conditions. Conclusions: Large amounts of puréed vegetables can be incorporated into various foods to decrease the energy density. This strategy can lead to substantial reductions in energy intakes and increases in vegetable intakes. This trial was registered at clinicaltrials.gov as NCT01165086.",
"title": "Hidden vegetables: an effective strategy to reduce energy intake and increase vegetable intake in adults"
},
{
"docid": "MED-1218",
"text": "There has been a recent increase in community-associated infections linked to methicillin-resistant Staphylococcus aureus (MRSA) and Clostridium difficile. It is established that both pathogens can be recovered from retail pork, although it is unclear to what degree contamination is acquired at the farm in comparison to that acquired during processing. To address this gap, the following study reports on the carriage of MRSA and C. difficile on pigs from birth through to the end of processing. C. difficile was isolated from 28 (93%) of 30 pigs at 1 day of age, but prevalence declined sharply to 1 of 26 by market age (188 days). MRSA prevalence peaked at 74 days of age, with 19 (68%) of 28 pigs testing positive, but declined to 3 of 26 at 150 days of age, with no pig being detected as positive at market age. At the processing facility, C. difficile was isolated from the holding area, with a single carcass testing positive for the pathogen at preevisceration. MRSA was primarily isolated from nasal swabs with 8 (31%) carcasses testing positive at postbleed, which increased to 14 (54%) positive at postscald tanks. Only one carcass (sampled at postbleed) tested positive for MRSA, with no recovery of the pathogen from environmental samples taken. C. difficile ribotype 078 predominated in the longitudinal portion of the study, accounting for all of the 68 isolates recovered from pigs. Only three C. difficile isolates, which were identified as ribotype 078, were recovered at the slaughterhouse. MRSA spa type 539 (t034) predominated in pigs on the farm and samples taken at the slaughterhouse, accounting for 80% of all isolates recovered. The study demonstrated that both C. difficile and MRSA acquired on the farm can be transferred through to processing, although no evidence for significant cross-contamination between carcasses or the slaughterhouse environment was evident.",
"title": "Longitudinal study of Clostridium difficile and Methicillin-resistant Staphylococcus aureus associated with pigs from weaning through to the end of..."
},
{
"docid": "MED-2972",
"text": "BACKGROUND: Elevated levels of lipids, such as total cholesterol (TC), low-density lipoprotein cholesterol (LDL), and triglycerides (TG), are widely recognized as risk factors for cardiovascular disease (CVD). Oxidized LDL (OxLDL) is an emerging risk factor considered relevant in oxidative stress and endothelial dysfunction, which is implicated in the progression of CVD. Consumption of a diet rich in polyphenols may be cardioprotective through its impact on oxidative stress and protecting LDL from oxidation. OBJECTIVES: This study was designed to test the ability of strawberry phenolic compounds to mitigate the postprandial effects of a high-fat meal on OxLDL as well as investigate the effects of phenolic compounds on lipid metabolism. METHODS: Twenty-four hyperlipidemic men and women (14 women, 10 men; mean age 50.9 +/- SD 15 years) were recruited to participate in this randomized, single-blind, placebo-controlled, 12-wk crossover trial. After a 10-day run-in period, subjects consumed either an active strawberry beverage (Str; containing 10 g freeze-dried fruit) or a placebo (Pbo) beverage matched in energy and macronutrient composition for 6 weeks. Twice before randomization and once at the 6-week crossover point, subjects received either Str or Pbo with a high-fat challenge meal (HFM). TC, LDL, high-density lipoprotein cholesterol, TG, and OxLDL were measured at defined intervals for 6 h before and after HFM challenge. Fasting concentrations of blood variables at 0, 6, and 12 weeks were compared to assess chronic intake of Str or Pbo. RESULTS: After the HFM during the run-in period, TG and OxLDL were lower after Str than Pbo (p = 0.005, p = 0.01, and p = 0.0008, respectively). HFM responses after 6 weeks of Str versus Pbo resulted in decreased lipid levels and a sex by treatment interaction for OxLDL (p = < 0.0001, and p = 0.0002). CONCLUSION: The present results support a role for strawberry in mitigating fed-state oxidative stressors that may contribute to atherogenesis.",
"title": "Strawberry modulates LDL oxidation and postprandial lipemia in response to high-fat meal in overweight hyperlipidemic men and women."
},
{
"docid": "MED-3161",
"text": "Intense exercise is directly related to muscular damage and oxidative stress due to excessive reactive oxygen species (ROS) in both, plasma and white blood cells. Nevertheless, exercise-derived ROS are essential to regulate cellular adaptation to exercise. Studies on antioxidant supplements have provided controversial results. The purpose of this study was to determine the effect of moderate antioxidant supplementation (lemon verbena extract) in healthy male volunteers that followed a 90-min running eccentric exercise protocol for 21 days. Antioxidant enzymes activities and oxidative stress markers were measured in neutrophils. Besides, inflammatory cytokines and muscular damage were determined in whole blood and serum samples, respectively. Intense running exercise for 21 days induced antioxidant response in neutrophils of trained male through the increase of the antioxidant enzymes catalase, glutathione peroxidase and glutathione reductase. Supplementation with moderate levels of an antioxidant lemon verbena extract did not block this cellular adaptive response and also reduced exercise-induced oxidative damage of proteins and lipids in neutrophils and decreased myeloperoxidase activity. Moreover, lemon verbena supplementation maintained or decreased the level of serum transaminases activity indicating a protection of muscular tissue. Exercise induced a decrease of interleukin-6 and interleukin-1β levels after 21 days measured in basal conditions, which was not inhibited by antioxidant supplementation. Therefore, moderate antioxidant supplementation with lemon verbena extract protects neutrophils against oxidative damage, decreases the signs of muscular damage in chronic running exercise without blocking the cellular adaptation to exercise.",
"title": "Effect of lemon verbena supplementation on muscular damage markers, proinflammatory cytokines release and neutrophils' oxidative stress in chronic ..."
},
{
"docid": "MED-3981",
"text": "The aim of this study was to investigate the relationship between child characteristics, parental and environmental factors and the occurrence of acute respiratory illness (ARI) and acute otitis media (AOM) among Finnish children attending day care centres (DCCs). The study was a cross-sectional questionnaire of 594 children aged 1-6 y from 18 DCCs in Helsinki, Finland. Recurrent (> or =4 diseases/y) ARI was present in 44% of the 1-3-y-olds and 23% of the 4-6-y-olds, and recurrent AOM in 15% and 2.5%, respectively. Parent atopic disease (odds ratio (OR) 1.53, p = 0.033), mother's academic education (OR 1.77, p = 0.008) and a medium length of DCC attendance compared to a short period (OR 1.67, p = 0.049) increased, while furry pets (OR 0.44, p = 0.003) and older child age (OR 0.38, p < 0.001) reduced the risk of recurrent ARI. Recurrent ARI (OR 3.96, p = 0.008), mother's academic education (OR 5.02, p = 0.003), and a medium length of DCC attendance compared to a short period (OR 3.34, p = 0.044) increased, while partial breastfeeding > or =6 months (OR 0.20, p = 0.002) and older child age (OR 0.05, p < 0.001) reduced the risk of recurrent AOM. Parental and environmental factors had a significant impact on recurrent ARI and AOM episodes in children attending DCCs. These risk factors should be considered in future studies intending to reduce DCC infections.",
"title": "Factors associated with acute respiratory illness in day care children."
},
{
"docid": "MED-2469",
"text": "The intestinal flora is considered to have an impact on the development of the immune system. In the anthroposophic lifestyle, a diet comprising vegetables spontaneously fermented by lactobacilli, and a restrictive use of antibiotics, anti-pyretics and vaccinations, is typical. The aim of this study was to assess the gut flora in infants in relation to certain lifestyle characteristics associated with anthroposophy. Sixty-nine children < 2 years of age with an anthroposophic lifestyle, and 59 infants of a similar age with a traditional lifestyle, were clinically examined and questionnaire replies assessed. Fecal samples were analyzed by bacterial enumeration, bacterial typing through biochemical fingerprinting and by measuring microflora-associated characteristics (MACs). The numbers of colony-forming units (CFU)/g of feces were significantly higher for enterococci and lactic acid bacteria in children who had never been exposed to antibiotics (5.5 x 107 vs. 2.1 x 107; p < 0.001 and 10 x 107 vs. 4.1 x 107; p < 0.01, respectively). Furthermore, the number of enterococci was significantly higher in breastfed and vegetarian infants (p < 0.01). The diversity (Simpson's diversity index) of lactobacilli, as determined by biochemical fingerprinting, was higher in infants born at home than in those born in hospital (p < 0.01). Several MACs were related to specific lifestyle features, and infants with an anthroposophic lifestyle had a higher proportion of acetic acid and a lower proportion of propionic acid in their stool as compared to the control children. In conclusion, lifestyle factors related to the anthroposophic way of life influenced the composition of the gut flora in the infants. These differences may contribute to the lower prevalence of atopic disease previously observed in children in anthroposophic families.",
"title": "An anthroposophic lifestyle and intestinal microflora in infancy."
},
{
"docid": "MED-870",
"text": "Ilex paraguariensis dried and minced leaves are made into a brewed tea, prepared in a sui generis manner by large populations in South America, having evolved from a tea drunk by the Guarani ethnic group to a beverage that has a social and almost ritualistic role in some South American modern societies. It is used both as a source of caffeine, in lieu or in parallel with tea and coffee, but also as a therapeutic agent for its alleged pharmacological properties. Although with some exceptions, research on biomedical properties of this herb has had a late start and strongly lags behind the impressive amount of literature on green tea and coffee. However, in the past 15 years, there was a several-fold increase in the literature studying Ilex paraguariensis properties showing effects such as antioxidant properties in chemical models and ex vivo lipoprotein studies, vaso-dilating and lipid reduction properties, antimutagenic effects, controversial association with oropharyngeal cancer, anti-glycation effects and weight reduction properties. Lately, promising results from human intervention studies have surfaced and the literature offers several developments on this area. The aim of this review is to provide a concise summary of the research published in the past three years, with an emphasis on translational studies, inflammation and lipid metabolism. Ilex paraguariensis reduces LDL-cholesterol levels in humans with Ilex paraguariensis dyslipoproteinemia and the effect is synergic with that of statins. Plasma antioxidant capacity as well as expression of antioxidant enzymes is positively modulated by intervention with Ilex paraguariensis in human cohorts. A review on the evidence implicating Ilex paraguariensis heavy consumption with some neoplasias show data that are inconclusive but indicate that contamination with alkylating agents during the drying process of the leaves should be avoided. On the other hand, several new studies confirm the antimutagenic effects of Ilex paraguariensis in different models, from DNA double breaks in cell culture models to mice studies. Novel interesting work has emerged showing significant effect on weight reduction both in mice and in rat models. Some mechanisms involved are inhibition of pancreatic lipase, activation of AMPK and uncoupling of electron transport. Intervention studies in animals have provided strong evidence of anti-inflammatory effects of Ilex paraguariensis, notably protecting cigarette-induced lung inflammation acting on macrophage migration and inactivating matrix-metalloproteinase. Research on the effects of Ilex paraguariensis in health and disease has confirmed its antioxidant, anti-inflammatory, antimutagenic and lipid-lowering activities. Although we are still waiting for the double-blind, randomized prospective clinical trial, the evidence seems to provide support for beneficial effects of mate drinking on chronic diseases with inflammatory component and lipid metabolism disorders. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.",
"title": "Recent advances on Ilex paraguariensis research: minireview."
},
{
"docid": "MED-1151",
"text": "Background: Organically produced foods are less likely than conventionally produced foods to contain pesticide residues. Methods: We examined the hypothesis that eating organic food may reduce the risk of soft tissue sarcoma, breast cancer, non-Hodgkin lymphoma and other common cancers in a large prospective study of 623 080 middle-aged UK women. Women reported their consumption of organic food and were followed for cancer incidence over the next 9.3 years. Cox regression models were used to estimate adjusted relative risks for cancer incidence by the reported frequency of consumption of organic foods. Results: At baseline, 30%, 63% and 7% of women reported never, sometimes, or usually/always eating organic food, respectively. Consumption of organic food was not associated with a reduction in the incidence of all cancer (n=53 769 cases in total) (RR for usually/always vs never=1.03, 95% confidence interval (CI): 0.99–1.07), soft tissue sarcoma (RR=1.37, 95% CI: 0.82–2.27), or breast cancer (RR=1.09, 95% CI: 1.02–1.15), but was associated for non-Hodgkin lymphoma (RR=0.79, 95% CI: 0.65–0.96). Conclusions: In this large prospective study there was little or no decrease in the incidence of cancer associated with consumption of organic food, except possibly for non-Hodgkin lymphoma.",
"title": "Organic food consumption and the incidence of cancer in a large prospective study of women in the United Kingdom"
},
{
"docid": "MED-4846",
"text": "The effects of a strict uncooked vegan diet on serum lipid and sterol concentrations were studied in patients with rheumatoid arthritis. The subjects were randomized into a vegan diet group (n 16), who consumed a vegan diet for 2-3 months, or into a control group (n 13), who continued their usual omnivorous diets. Serum total and LDL-cholesterol and -phospholipid concentrations were significantly decreased by the vegan diet. The levels of serum cholestanol and lathosterol also decreased, but serum cholestanol:total cholesterol and lathosterol:total cholesterol did not change. The effect of a vegan diet on serum plant sterols was divergent as the concentration of campesterol decreased while that of sitosterol increased. This effect resulted in a significantly greater sitosterol:campesterol value in the vegan diet group than in the control group (1.48 (SD 0.39) v. 0.72 (SD 0.14); P < 0.001). A higher concentration of campesterol compared with sitosterol is normal in omnivorous subjects and can be explained by lower absorption and esterification rates of sitosterol. Our results suggest that a strict uncooked vegan diet changes the relative absorption rates of these sterols and/or their biliary clearance.",
"title": "Divergent changes in serum sterols during a strict uncooked vegan diet in patients with rheumatoid arthritis."
},
{
"docid": "MED-2122",
"text": "OBJECTIVE: To clarify the hormonal context of breast cancer etiology we used data from a large, population-based case-control study to investigate the relationship between breast cancer risk and a history of diabetes mellitus, disorders associated with estrogen stimulation (uterine fibroids, endometriosis, gallstones), and disorders associated with androgen stimulation (acne, hirsutism, and polycystic ovaries). METHODS: Breast cancer patients between 50 and 75 years old were identified from state-wide tumor registries in Wisconsin, Massachusetts, and New Hampshire; controls were randomly selected from drivers' license lists (age less than 65) or Medicare enrollment files (age 65-74). Information on reproductive history, medical history, and personal habits was obtained by telephone interview. A total of 5659 cases and 5928 controls were interviewed and provided suitable data. RESULTS: There was no overall association between breast cancer risk and reported history of diabetes mellitus, endometriosis, uterine fibroids, gallstones, or cholecystectomy. However, the disorders with androgenic associations all conferred an increased risk: the overall odds ratio (OR) for a history of acne was 1.4 (95% CI 1.0-1.9), that for hirsutism was 1.2 (95% CI 0.81-1.8), and that for polycystic ovaries 1.6 (95% CI 0.8-3.2). Diabetes mellitus diagnosed before age 35 conferred an odds ratio of 0.52 (95% 0.25-1.1), while diabetes diagnosed at a later age was associated with an increased risk (OR = 1.2, 95% CI 1.0-1.4). CONCLUSIONS: Androgen-related phenomena are likely to be important in the etiology of breast cancer.",
"title": "Metabolic disorders and breast cancer risk (United States)."
},
{
"docid": "MED-1338",
"text": "Objective To examine whether high milk consumption is associated with mortality and fractures in women and men. Design Cohort studies. Setting Three counties in central Sweden. Participants Two large Swedish cohorts, one with 61 433 women (39-74 years at baseline 1987-90) and one with 45 339 men (45-79 years at baseline 1997), were administered food frequency questionnaires. The women responded to a second food frequency questionnaire in 1997. Main outcome measure Multivariable survival models were applied to determine the association between milk consumption and time to mortality or fracture. Results During a mean follow-up of 20.1 years, 15 541 women died and 17 252 had a fracture, of whom 4259 had a hip fracture. In the male cohort with a mean follow-up of 11.2 years, 10 112 men died and 5066 had a fracture, with 1166 hip fracture cases. In women the adjusted mortality hazard ratio for three or more glasses of milk a day compared with less than one glass a day was 1.93 (95% confidence interval 1.80 to 2.06). For every glass of milk, the adjusted hazard ratio of all cause mortality was 1.15 (1.13 to 1.17) in women and 1.03 (1.01 to 1.04) in men. For every glass of milk in women no reduction was observed in fracture risk with higher milk consumption for any fracture (1.02, 1.00 to 1.04) or for hip fracture (1.09, 1.05 to 1.13). The corresponding adjusted hazard ratios in men were 1.01 (0.99 to 1.03) and 1.03 (0.99 to 1.07). In subsamples of two additional cohorts, one in males and one in females, a positive association was seen between milk intake and both urine 8-iso-PGF2α (a biomarker of oxidative stress) and serum interleukin 6 (a main inflammatory biomarker). Conclusions High milk intake was associated with higher mortality in one cohort of women and in another cohort of men, and with higher fracture incidence in women. Given the observational study designs with the inherent possibility of residual confounding and reverse causation phenomena, a cautious interpretation of the results is recommended.",
"title": "Milk intake and risk of mortality and fractures in women and men: cohort studies"
},
{
"docid": "MED-762",
"text": "The Ethiopian Field Epidemiology and Laboratory Training Program (EFELTP) is a comprehensive two-year competency-based training and service program designed to build sustainable public health expertise and capacity. Established in 2009, the program is a partnership between the Ethiopian Federal Ministry of Health, the Ethiopian Health and Nutrition Research Institute, Addis Ababa University School of Public Health, the Ethiopian Public Health Association and the US Centers of Disease Control and Prevention. Residents of the program spend about 25% of their time undergoing didactic training and the 75% in the field working at program field bases established with the MOH and Regional Health Bureaus investigating disease outbreaks, improving disease surveillance, responding to public health emergencies, using health data to make recommendations and undertaking other field Epidemiology related activities on setting health policy. Residents from the first 2 cohorts of the program have conducted more than 42 outbreaks investigations, 27analyses of surveillance data, evaluations of 11 surveillance systems, had28oral and poster presentation abstracts accepted at 10 scientific conferences and submitted 8 manuscripts of which 2are already published. The EFELTP has provided valuable opportunities to improve epidemiology and laboratory capacity building in Ethiopia. While the program is relatively young, positive and significant impacts are assisting the country better detect and respond to epidemics and address diseases of major public health significance.",
"title": "The Ethiopian Field Epidemiology and Laboratory Training Program: strengthening public health systems and building human resource capacity."
},
{
"docid": "MED-2115",
"text": "Dietary PUFA, mainly those of the n-3 family, are known to play essential roles in the maintenance of energy balance and in the reduction of body fat deposition through the upregulation of mitochondrial uncoupling that is the main source of reactive oxygen species. We hypothesized that rat supplementation with raw donkey's milk (DM), characterized by low-fat content and higher n3:n6 ratio, may affect energy balance, lipid metabolism, and prooxidant status as compared to animals treated with cow's milk. In the present study, the effects of drinking raw DM (for 4 weeks) on energy balance, lipid metabolism, antiinflammatory, and antioxidant/detoxifying defences was compared to that produced by rat intake of an iso-energetic amount of raw cow's milk. The hypolipidemic effect produced by DM paralleled with the enhanced mitochondrial activity/proton leakage and with the increased activity or expression of mitochondrial markers namely, carnitine palmitoyl transferase and uncoupling protein 2. The association of decreased energy efficiency with reduced proinflammatory signs (TNF-α and LPS levels) with the significant increase antioxidant (total thiols) and detoxifying enzyme activities (glutathione-S-transferase NADH quinone oxidoreductase) in DM-treated animals, indicated that beneficial effects were attributable, at least in part, to the activation of nuclear factor 2 erythroid-related factor 2 pathway. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",
"title": "Diet supplementation with donkey milk upregulates liver mitochondrial uncoupling, reduces energy efficiency and improves antioxidant and antiinflam..."
},
{
"docid": "MED-2052",
"text": "The addition of direct-acting antivirals (DAAs) to hepatitis C virus (HCV) treatment regimens has made treatment more effective and patient management more complex. Shepherding patients through a full course of HCV therapy requires motivation and involvement on the part of the patient and the physician. Indeed, physician inexperience and lack of confidence in guiding patients through the challenges of treatment appears to be a primary reason for early discontinuation of therapy. Among the many complications of HCV treatment that must be managed efficiently and effectively are depression and other psychiatric disorders; hematologic abnormalities including DAA- and ribavirin-associated anemia and peginterferon alfa-associated neutropenia and thrombocytopenia; rash and drug eruptions, including telaprevir-associated rash; and weight loss. Practical considerations in management of these common complications are offered. This article summarizes a presentation by Kenneth E. Sherman, MD, PhD, at the IAS-USA live continuing medical education course held in New York in June 2012.",
"title": "Managing adverse effects and complications in completing treatment for hepatitis C virus infection."
},
{
"docid": "MED-4969",
"text": "Transmission of viruses, bacteria, and parasites to food by way of improperly washed hands is a major contributing factor in the spread of foodborne illnesses. Field observers have assessed compliance with hand washing regulations, yet few studies have included consideration of frequency and methods used by sectors of the food service industry or have included benchmarks for hand washing. Five 3-h observation periods of employee (n = 80) hand washing behaviors during menu production, service, and cleaning were conducted in 16 food service operations for a total of 240 h of direct observation. Four operations from each of four sectors of the retail food service industry participated in the study: assisted living for the elderly, childcare, restaurants, and schools. A validated observation form, based on 2005 Food Code guidelines, was used by two trained researchers. Researchers noted when hands should have been washed, when hands were washed, and how hands were washed. Overall compliance with Food Code recommendations for frequency during production, service, and cleaning phases ranged from 5% in restaurants to 33% in assisted living facilities. Procedural compliance rates also were low. Proposed benchmarks for the number of times hand washing should occur by each employee for each sector of food service during each phase of operation are seven times per hour for assisted living, nine times per hour for childcare, 29 times per hour for restaurants, and 11 times per hour for schools. These benchmarks are high, especially for restaurant employees. Implementation would mean lost productivity and potential for dermatitis; thus, active managerial control over work assignments is needed. These benchmarks can be used for training and to guide employee hand washing behaviors.",
"title": "Hand washing frequencies and procedures used in retail food services."
},
{
"docid": "MED-1638",
"text": "OBJECTIVE: Migratory capacity of endothelial progenitor cells (EPCs) and mature endothelial cells (ECs) is a key prerequisite for endothelial repair after denuding injury or endothelial damage. METHODS AND RESULTS: We demonstrate that caffeine in physiologically relevant concentrations (50 to 100 micromol/L) induces migration of human EPCs as well as mature ECs. In patients with coronary artery disease (CAD), caffeinated coffee increased caffeine serum concentration from 2 micromol/L to 23 micromol/L, coinciding with a significant increase in migratory activity of patient-derived EPCs. Decaffeinated coffee neither affected caffeine serum levels nor migratory capacity of EPCs. Treatment with caffeine for 7 to 10 days in a mouse-model improved endothelial repair after denudation of the carotid artery. The enhancement of reendothelialization by caffeine was significantly reduced in AMPK knockout mice compared to wild-type animals. Transplantation of wild-type and AMPK(-/-) bone marrow into wild-type mice revealed no difference in caffeine challenged reendothelialization. ECs which were depleted of mitochondrial DNA did not migrate when challenged with caffeine, suggesting a potential role for mitochondria in caffeine-dependent migration. CONCLUSIONS: These results provide evidence that caffeine enhances endothelial cell migration and reendothelialization in part through an AMPK-dependent mechanism, suggesting a beneficial role for caffeine in endothelial repair.",
"title": "Caffeine enhances endothelial repair by an AMPK-dependent mechanism."
},
{
"docid": "MED-2585",
"text": "Inositol hexaphosphate (IP6) is a naturally occurring polyphosphorylated carbohydrate that is present in substantial amounts in almost all plant and mammalian cells. It was recently recognized to possess multiple biological functions. A striking anticancer effect of IP6 was demonstrated in different experimental models. Inositol is also a natural constituent possessing moderate anticancer activity. The most consistent and best anticancer results were obtained from the combination of IP6 plus inositol. In addition to reducing cell proliferation, IP6 increases differentiation of malignant cells, often resulting in a reversion to normal phenotype. Exogenously administered IP6 is rapidly taken into the cells and dephosphorylated to lower-phosphate inositol phosphates, which further interfere with signal transduction pathways and cell cycle arrest. Enhanced immunity and antioxidant properties can also contribute to tumor cell destruction. However, the molecular mechanisms underlying this anticancer action are not fully understood. Because it is abundantly present in regular diet, efficiently absorbed from the gastrointestinal tract, and safe, IP6 holds great promise in our strategies for the prevention and treatment of cancer. IP6 plus inositol enhances the anticancer effect of conventional chemotherapy, controls cancer metastases, and improves the quality of life, as shown in a pilot clinical trial. The data strongly argue for the use of IP6 plus inositol in our strategies for cancer prevention and treatment. However, the effectiveness and safety of IP6 plus inositol at therapeutic doses needs to be determined in phase I and phase II clinical trials in humans.",
"title": "Cancer inhibition by inositol hexaphosphate (IP6) and inositol: from laboratory to clinic."
},
{
"docid": "MED-4226",
"text": "Bone, as well as liver and lung, is one of the most preferential metastatic target sites for cancers including breast, prostate, and lung cancers and the consequences are always devastating. Like other metastasis, breast cancer bone metastasis consists of several steps from the escape of primary site to the colonization in target site. This review focuses on several key steps including: 1. Invasion and escape from primary tumor site. 2. Target migration toward bone. 3. Specific adhesion and arrest in bone. 4. Establishment of metastasis in bone. The factors involved in this process will provide good targets for therapy. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.",
"title": "Mechanisms of breast cancer bone metastasis."
},
{
"docid": "MED-5120",
"text": "Human gammadeltaT lymphocytes are a subset of T cells and are a first line of defense against microbes and tumors. These gammadeltaT cells can be primed by nitrogen-containing bisphosphonates, and certain short-chain alkylamines. These primed gammadeltaT cells have an enhanced capacity to proliferate and to secrete cytokines upon ex vivo exposure to a wide variety of microbes and tumor cells. The largest dietary source of alkylamines is L-theanine, an amino acid unique to tea beverages that is catabolized to ethylamine. Supplementation of subjects with capsules containing L-theanine and catechins has recently been shown to decrease the incidence of cold and flu symptoms, while enhancing gammadeltaT cell function.",
"title": "L-theanine intervention enhances human gammadeltaT lymphocyte function."
}
] |
10500
|
How do government bond yields work?
|
[
{
"docid": "189761",
"text": "Imagine a $1,000 face value bond paying 10% interest semi-annually. That means every 6 months there is $50 being paid. Now, if the price of that bond doubled to $2,000, what is the yield? It is still paying $50 every 6 months but now sports a 5% yield as the price went up a great deal. Similarly, if the price of the bond was cut in half to $500, now it is yielding 20% because it is still paying out the $50 every 6 months. The dollar figure is fixed. What percentage of the price it is can vary and that is why there is the inverse relationship between prices and yields. Note that the length of the bond isn't mentioned here where while usually longer bonds will have higher yields, there can be inverted yield curves as well as calls on some bonds. Also, inflation-indexed and convertible bonds could have different calculations used as principal adjustments or possible conversion to stock can change a perception on the overall return.",
"title": ""
},
{
"docid": "466315",
"text": "Why does the rising price of a bond pushes it's yield down? The bond price and its yield are linked; if one goes up, the other must go down. This is because the cash flows from the bond are fixed, predetermined. The market price of the bond fluctuates. Now what if people are suddenly willing to pay more for the same fixed payments? It must mean that the return, i.e. the yield, will be lower. Here we see that risk associated with the bonds in question has skyrocketed, and thus bonds' returns has skyrocketed, too. Am I right? The default risk has increased, yes. Now, I assume that bonds' price is determined by the market (issued by a state, traded at the market). Is that correct? Correct, as long as you are talking about the market price. Then who determines bonds' yields? I mean, isn't it fixed? Or - in the FT quote above - they are talking about the yields for the new bonds issued that particular month? The yield is not fixed - the cash flows are. Yield is the internal rate of return. See my answer above to your first question.",
"title": ""
}
] |
[
{
"docid": "416513",
"text": "Yield is the term used to describe how much income the bond will generate if the bond was purchased at a particular moment in time. If I pay $100 for a one year, $100 par value bond that pays 5% interest then the bond yields 5% since I will receive $5 from a $100 investment if I held the bond to maturity. If I pay $90 for the same one year bond then the bond yields 17% since I will receive $15 from a $90 investment if I held the bond to maturity. There are many factors that affect what yield creditors will accept: It is the last bullet that ultimately determines yield. The other factors feed into the creditor’s desire to hold money today versus receiving money in the future. I desire money in my hand more than a promise to receive money in the future. In order to entice me to lend my money someone must offer me an incentive. Thus, they must offer me more money in the future in order for me to part with money I have. A yield curve is a snapshot of the yields for different loan durations. The x-axis is the amount of time left on the bond while the y-axis is the yield. The most cited yield curve is the US treasury curve which displays the yields for loans to the US government. The yield curve changes while bonds are being traded thus it is always a snapshot of a particular moment in time. Short term loans typically have less yield than longer term loans since there is less uncertainty about the near future. Yield curves will flatten or slightly invert when creditors desire to keep their money instead of loaning it out. This can occur because of a sudden disruption in the market that causes uncertainty about the future which leads to an increase in the demand for cash on hand. The US government yield curve should be looked at with some reservation however since there is a very large creditor to the US government that has the ability to loan the government an unlimited amount of funds.",
"title": ""
},
{
"docid": "127434",
"text": "You’ve really got three or four questions going here… and it’s clear that a gap in understanding one component of how bonds work (pricing) is having a ripple effect across the other facets of your question. The reality is that everybody’s answers so far touch on various pieces of your general question, but maybe I can help by integrating. So, let’s start by nailing down what your actual questions are: 1. Why do mortgage rates (tend to) increase when the published treasury bond rate increases? I’m going to come back to this, because it requires a lot of building blocks. 2. What’s the math behind a bond yield increasing (price falling?) This gets complicated, fast. Especially when you start talking about selling the bond in the middle of its time period. Many people that trade in bonds use financial calculators, Excel, or pre-calculated tables to simplify or even just approximate the value of a bond. But here’s a simple example that shows the math. Let’s say we’ve got a bond that is issued by… Dell for $10,000. The company will pay it back in 5 years, and it is offering an 8% rate. Interest payments will only be paid annually. Remember that the amount Dell has promised to pay in interest is fixed for the life of the bond, and is called the ‘coupon’ rate. We can think about the way the payouts will be paid in the following table: As I’m sure you know, the value of a bond (its yield) comes from two sources: the interest payments, and the return of the principal. But, if you as an investor paid $14,000 for this bond, you would usually be wrong. You need to ‘discount’ those amounts to take into account the ‘time value of money’. This is why when you are dealing in bonds it is important to know the ‘coupon rate’ (what is Dell paying each period?). But it is also important to know your sellers’/buyers’ own personal discount rates. This will vary from person to person and institution to institution, but it is what actually sets the PRICE you would buy this bond for. There are three general cases for the discount rate (or the MARKET rate). First, where the market rate == the coupon rate. This is known as “par” in bond parlance. Second, where the market rate < the coupon rate. This is known as “premium” in bond parlance. Third, where the market rate > coupon rate. This is known as a ‘discount’ bond. But before we get into those in too much depth, how does discounting work? The idea behind discounting is that you need to account for the idea that a dollar today is not worth the same as a dollar tomorrow. (It’s usually worth ‘more’ tomorrow.) You discount a lump sum, like the return of the principal, differently than you do a series of equal cash flows, like the stream of $800 interest payments. The formula for discounting a lump sum is: Present Value=Future Value* (1/(1+interest rate))^((# of periods)) The formula for discounting a stream of equal payments is: Present Value=(Single Payment)* (〖1-(1+i)〗^((-n))/i) (i = interest rate and n = number of periods) **cite investopedia So let’s look at how this would look in pricing the pretend Dell bond as a par bond. First, we discount the return of the $10,000 principal as (10,000 * (1 / 1.08)^5). That equals $6,807.82. Next we discount the 5 equal payments of $800 as (800* (3.9902)). I just plugged and chugged but you can do that yourself. That equals $3,192.18. You may get slightly different numbers with rounding. So you add the two together, and it says that you would be willing to pay ($6,807.82 + $3,192.18) = $10,000. Surprise! When the bond is a par bond you’re basically being compensated for the time value of money with the interest payments. You purchase the bond at the ‘face value’, which is the principal that will be returned at the end. If you worked through the math for a 6% discount rate on an 8% coupon bond, you would see that it’s “premium”, because you would pay more than the principal that is returned to obtain the bond [10,842.87 vs 10,000]. Similarly, if you work through the math for a 10% discount rate on an 8% coupon bond, it’s a ‘discount’ bond because you will pay less than the principal that is returned for the bond [9,241.84 vs 10,000]. It’s easy to see how an investor could hold our imaginary Dell bond for one year, collect the first interest payment, and then sell the bond on to another investor. The mechanics of the calculations are the same, except that one less interest payment is available, and the principal will be returned one year sooner… so N=4 in both formulae. Still with me? Now that we’re on the same page about how a bond is priced, we can talk about “Yield To Maturity”, which is at the heart of your main question. Bond “yields” like the ones you can access on CNBC or Yahoo!Finance or wherever you may be looking are actually taking the reverse approach to this. In these cases the prices are ‘fixed’ in that the sellers have listed the bonds for sale, and specified the price. Since the coupon values are fixed already by whatever organization issued the bond, the rate of return can be imputed from those values. To do that, you just do a bit of algebra and swap “present value” and “future value” in our two equations. Let’s say that Dell has gone private, had an awesome year, and figured out how to make robot unicorns that do wonderful things for all mankind. You decide that now would be a great time to sell your bond after holding it for one year… and collecting that $800 interest payment. You think you’d like to sell it for $10,500. (Since the principal return is fixed (+10,000); the number of periods is fixed (4); and the interest payments are fixed ($800); but you’ve changed the price... something else has to adjust and that is the discount rate.) It’s kind of tricky to actually use those equations to solve for this by hand… you end up with two equations… one unknown, and set them equal. So, the easiest way to solve for this rate is actually in Excel, using the function =RATE(NPER, PMT, PV, FV). NPER = 4, PMT = 800, PV=-10500, and FV=10000. Hint to make sure that you catch the minus sign in front of the present value… buyer pays now for the positive return of 10,000 in the future. That shows 6.54% as the effective discount rate (or rate of return) for the investor. That is the same thing as the yield to maturity. It specifies the return that a bond investor would see if he or she purchased the bond today and held it to maturity. 3. What factors (in terms of supply and demand) drive changes in the bond market? I hope it’s clear now how the tradeoff works between yields going UP when prices go DOWN, and vice versa. It happens because the COUPON rate, the number of periods, and the return of principal for a bond are fixed. So when someone sells a bond in the middle of its term, the only things that can change are the price and corresponding yield/discount rate. Other commenters… including you… have touched on some of the reasons why the prices go up and down. Generally speaking, it’s because of the basics of supply and demand… higher level of bonds for sale to be purchased by same level of demand will mean prices go down. But it’s not ‘just because interest rates are going up and down’. It has a lot more to do with the expectations for 1) risk, 2) return and 3) future inflation. Sometimes it is action by the Fed, as Joe Taxpayer has pointed out. If they sell a lot of bonds, then the basics of higher supply for a set level of demand imply that the prices should go down. Prices going down on a bond imply that yields will go up. (I really hope that’s clear by now). This is a common monetary lever that the government uses to ‘remove money’ from the system, in that they receive payments from an investor up front when the investor buys the bond from the Fed, and then the Fed gradually return that cash back into the system over time. Sometimes it is due to uncertainty about the future. If investors at large believe that inflation is coming, then bonds become a less attractive investment, as the dollars received for future payments will be less valuable. This could lead to a sell-off in the bond markets, because investors want to cash out their bonds and transfer that capital to something that will preserve their value under inflation. Here again an increase in supply of bonds for sale will lead to decreased prices and higher yields. At the end of the day it is really hard to predict exactly which direction bond markets will be moving, and more importantly WHY. If you figure it out, move to New York or Chicago or London and work as a trader in the bond markets. You’ll make a killing, and if you’d like I will be glad to drive your cars for you. 4. How does the availability of money supply for banks drive changes in other lending rates? When any investment organization forms, it builds its portfolio to try to deliver a set return at the lowest risk possible. As a corollary to that, it tries to deliver the maximum return possible for a given level of risk. When we’re talking about a bank, DumbCoder’s answer is dead on. Banks have various options to choose from, and a 10-year T-bond is broadly seen as one of the least risky investments. Thus, it is a benchmark for other investments. 5. So… now, why do mortgage rates tend to increase when the published treasury bond yield rate increases? The traditional, residential 30-year mortgage is VERY similar to a bond investment. There is a long-term investment horizon, with fixed cash payments over the term of the note. But the principal is returned incrementally during the life of the loan. So, since mortgages are ‘more risky’ than the 10-year treasury bond, they will carry a certain premium that is tied to how much more risky an individual is as a borrower than the US government. And here it is… no one actually directly changes the interest rate on 10-year treasuries. Not even the Fed. The Fed sets a price constraint that it will sell bonds at during its periodic auctions. Buyers bid for those, and the resulting prices imply the yield rate. If the yield rate for current 10-year bonds increases, then banks take it as a sign that everyone in the investment community sees some sign of increased risk in the future. This might be from inflation. This might be from uncertain economic performance. But whatever it is, they operate with some rule of thumb that their 30-year mortgage rate for excellent credit borrowers will be the 10-year plus 1.5% or something. And they publish their rates.",
"title": ""
},
{
"docid": "231268",
"text": "Companies do not support their stock. Once the security is out on the wild (market), its price fluctuates according to what investors think they are worth. Support is a whole different concept, financially speaking: Support or support level refers to the price level below which, historically, a stock has had difficulty falling. It is the level at which buyers tend to enter the stock. So it is the lowest assumed price for that stock. Once it reaches its price, buyers will rush to the stock, raising its price. The company wants to keep the stock price at acceptable levels, as it can be seen as the general view of the company's health. Also several employees/executives in the company have stock or stock options, so it is in their interest to keep their stock price up. A bond that goes down in value may indicate a believe the bond issuer (government in this case) won't honor the bond when it matures. As for bonds, there is a wealth of reading in this site: Can someone explain how government bonds work? Who sets the prices on government bonds? Basic understanding of bonds, values, rates and yields",
"title": ""
},
{
"docid": "285176",
"text": "The assumption that bonds have been issued with a negative coupon is not correct, or at least is has not occurred thus far. We'll look at this future possibility in the final paragraph. For now, lets look at the current bond market. The issuance of government bonds which carry a negative gross redemption yield is the result of governments issuing bonds at an issue price which exceed the nominal/redemption price and any coupon yield receivable over the life of the bond. I can find no instances of bonds with a negative coupon, though many have tiny positive coupon yields. The short seller of a bond with a negative gross redemption yield will be liable to pay the buyer the interest amount determined by the coupon. If the short seller has borrowed the bonds in order to sell them, then the short seller will receive the interest due from the lender to offset the interest paid to the buyer. If the short seller has not borrowed the bonds, but has sold them using some sort of synthetic contract such as a Contract for Difference, then the short seller will pay the coupon without receiving any offsetting payment. I thought this was an interesting question and it will be interesting to see if, at some time in the future, governments do ever issue bonds with a negative coupon. To date, this does not appear to have happened. So what would happen if we assume that a government issues a bond with a negative coupon. The buyer of the bond would be required to pay the equivalent yield to the government according to the bond contract specification. If an investor sells short such a bond, they would then become entitled to receive the interest from the buyer. If they have borrowed the bonds in order to sell them short, then they would pay any interest received back to the lender - this chain should eventually end with the ultimate owner/lender paying the government their dues. If they have sold short using a synthetic contract, then presumably they would keep the interest from themselves.",
"title": ""
},
{
"docid": "388391",
"text": "\"So \"\"Operation Twist\"\" is actually a pretty simple concept. Here's the break down: The Fed sells short-term treasury bonds that it already holds on its books. Short-term treasury bonds refer to - bonds that mature in less than three years. Then: Uses that money to buy long term treasury bonds. Long-term treasury bonds refer to - bonds that mature in six to 30 years The reason: The fed buys these longer-term treasuries to lower longer-term interest rates and encourage more borrowing and spending. Diving deeper into how it works: So the Fed can easily determine short-term rates by using the Federal funds rate this rate has a direct effect on the following: However this does not play a direct role in influencing the rate of long-term loans (what you might pay on a 30-year fixed mortgage). Instead, long-term rates are determined by investors who buy and sell bonds in the bond market, which changes daily. These bond yields fluctuate depending on the health of the economy and inflation. However, the Fed funds rate does play an indirect role in these rates. So now that we know a little more about what effects what rate, why does lower long-term rates in treasuries influence my 30yr fixed mortgage? Well when you are looking for a loan you are entering a market and competing against other people, by people I mean anyone looking for money (e.g: my grandmother, companies, or the US government). The bank that lends you money has to decide weather the deal you are offering them is better then another deal on the market. If the risk of lending to one person is the same as the risk of lending to another, the bank will make whichever loan yields the higher interest rate. The U.S. government is considered a very safe borrower, so much so that government bonds are considered almost “risk free”, but because of the lower risk the rate of return is lower. So now the bank has to factor in this risk and make its decision weather to lend you money, or the government. So, if the government were to go to the market and buy its own long-term bonds it is adding demand in the market causing the price of the bond to rise in effect lowering the interest rate (when price goes up, yield goes down). So when you go back and ask for a loan it has to re-evaluate and decide \"\"Is it worth giving this money to Joe McFreeBeer instead and collecting a higher yield?\"\" (After all, Joe McFreeBeer is a nice guy). Here's an example: Lets say the US has a rating of 10 out of 10 and its bonds pay a 2% yield. Now lets say for each lower mark in rating the bank will lend at a minimum of 1% higher and your rating is 8 of 10. So if you go to market, the lowest rate you can get will be 4%. Now lets say price rises on the US treasury and causes the rate to go down by 1%. In this scenario you will now be able to get a loan for 3% and someone with a rating of 7 of 10 would be able to get that 4% loan. Here's some more info and explinations: Why is the Government Buying Long-Term Bonds? What Is 'Operation Twist'? A Q&A on US Fed Program Federal Reserve for Beginners Federal Open Market Committee\"",
"title": ""
},
{
"docid": "144177",
"text": "\"If you owned a bank how would you invest the bank's money? Typically banks are involved in loaning out money to businesses, people, and government at a higher interest rate then what they are paying to depositors. This is the spread and how they make money. If the bank determines that the yields on government bonds is more attractive then loaning the money out to businesses and people then the bank will purchase government bonds. It can also decide the other way. In this manner the mortgage and bond markets are always competing for capital and tend to offer very similar yields. Certain banks have the unique privilege of being able to borrow money from the FED at the Federal Funds rate and use this money to purchase government debt or loan it out to other banks or purchase other debt products. In this manner you see a high correlation between the FED funds rate, mortgage rates, and treasury yields. Other political factors include legislation that encourages mortgage lending (see Community Reinvestment Act) where banks may not have made the loans without said legislation. In short, keep your eye on the FED and ask yourself: \"\"Does the FED want rates to rise?\"\" and \"\"Can the US government afford rising rates?\"\" The answer to these two questions is no. However, the FED may be pressured to \"\"stop the presses\"\" if inflation becomes unwieldy and the FED actually starts to care about food and energy prices. So far this hasn't been the case.\"",
"title": ""
},
{
"docid": "446214",
"text": "\"What is a bond price? A bond is an asset, and like any tradeable asset it has a price. If I hold $10K face value of a certain GM bond, then I would be willing to sell it at some price, which may be more or less than $10K. Whoever is willing to sell it for the lowest amount determines the price. The price is determined by the market, just as all prices are. It's what you can sell a bond for. Bond prices may be quoted in various funny ways, like as a discount or premium relative to the face value or as a premium over a treasury, but at the end it all should be converted to how much you have to pay today. In this case, it's how much you would pay today to get a set of future coupon and principal payments. What is Yield to Maturity? A bond is a contract entitling you to a certain set of predefined cash flows. If you take that set of cash flows and discount them using a single rate at all maturities such that the discounted value is equal to the price, the single rate you have identified is the YTM. Mathematically, this is the same as finding the IRR (internal rate of return) of some set of cash flows. In this case the cash flows are the coupons and principal repayment. Other bond concepts. Note that the other aspects of a bond, like maturity, coupon rate, and face value, are immutably written into the bond contract. All they do is define what payments the bond entitles the owner to. They don't say how much someone would pay today in order to be entitled to those payments. One can't know how much a future payment is worth without discounting. If you know the appropriate discount rate at every relevant maturity, you could calculate the fair price of a bond. That's the other direction. YTM looks at the market price and associated cash flows and imputes what single discount rate would make that price fair. What is YTM good for? Recall what I said about IRR above. Why would anyone want to know what discount rate equates the cash flows of a project to its cost? Because it's an easy way to summarize how profitable the project is expected to be. YTM is a quick way to summarize the yield one would get on a bond if they were to buy it today and hold to maturity. If one bond has a higher YTM than another, than heuristically we believe it pays out more and should be associated with greater risk if the market is working properly. It can be used to compare bonds or to look at how changes in bond prices are affecting expected yields. Ask yourself, how would you compare two different bonds with different maturities and coupon rates? Which one is riskier or more profitable? The simplest way to summarize this information is with the yield to maturity. YTM is used frequently enough that when you just say a bond's \"\"yield,\"\" people will assume you are talking about its yield to maturity. What is YTM not good for? One thing to be wary of is using YTM as a discount rate. It looks like a discount rate but it works for that bond and that bond only. In reality each individual coupon payment has a true discount rate, and the discount rate at each horizon is different from each other horizon. Those are true discount rates that can be applied to any cash flow of similar risk to get the right price. We can think of YTM as some kind of average of those discount rates that produces the correct price for that bond only. You should never use it for discounting something else.\"",
"title": ""
},
{
"docid": "342485",
"text": "just pick a good bond and invest all your money there (since they're fairly low risk) No. That is basically throwing away your money and why would you do that. And who told you they are low risk. That is a very wrong premise. What factors should I consider in picking a bond and how would they weigh against each other? Quite a number of them to say, assuming these aren't government bonds(US, UK etc) How safe is the institution issuing the bond. Their income, business they are in, their past performance business wise and the bonds issued by them, if any. Check for the bond ratings issued by the rating agencies. Read the prospectus and check for any specific conditions i.e. bonds are callable, bonds can be retired under certain conditions, what happens if they default and what order will you be reimbursed(senior debt take priority). Where are interest rates heading, which will decide the price you are paying for the bond. And also the yield you will derive from the bond. How do you intend to invest the income, coupon, you will derive from the bonds. What is your time horizon to invest in bonds and similarly the bond's life. I have invested in stocks previously but realized that it isn't for me Bonds are much more difficult than equities. Stick to government bonds if you can, but they don't generate much income, considering the low interest rates environment. Now that QE is over you might expect interest rates to rise, but you can only wait. Or go for bonds from stable companies i.e. GE, Walmart. And no I am not saying you buy their bonds in any imaginable way.",
"title": ""
},
{
"docid": "395111",
"text": "The 10yr bond pays coupons semi annually. The yield % is what you would get annually if you hold the bond to full term. The coupon payment won't be exactly 1.65%/2 because of how bond pricing and yields work. The yield commonly quoted does not tell you how much each interest payment is. You have to look at the price and coupon of a specific individual bond. The rate you see is the market equilibrium yield at the present. Example, I offer two different people two different bonds. Joe buys a 10yr bond paying 5% coupons semi annually at a par value of $1000. I charge him $1000. Bob wants to buy a 10yr bond paying 10% coupons semi annually at a par value of $1000. I charge him $1500 for this. The yield is similar between the two (not equal due to math details but lets assume). So at the end of 10 yrs, the two have roughly the same total amount of $. Bob's paid more each year but he paid more up front. This is why the federal govt can issue bonds with diff coupons and the market prices them so the yield rises/falls to the market clearing yield.",
"title": ""
},
{
"docid": "498645",
"text": "\"Bonds might not be simple, but in general there are only a few variables that need to be understood: bid, coupon (interest) rate, maturity, and yield. Bond tables clearly lay those out, and if you're talking about government bonds a lot of things (like convertibles) don't apply (although default is still a concern). This might be overly simplistic, but I view ETF's primarily as an easy way to bring somewhat esoteric instruments (like grain futures) into the easily available markets of Nasdaq and the NYSE. That they got \"\"enhanced\"\" with leveraged funds and the such is interesting, but perhaps not the original intent of the instrument. Complicating your situation a bit more is the fee that gets tacked onto the ETF. Even Vanguard government bond funds hang out north of 0.1%. That's not huge, but it's not particularly appealing either considering that (unlike rounding up live cattle futures), it's not that much work to buy US government bonds, so the expense might not seem worth it to someone who's comfortable purchasing the securities directly. I'd be interested to see someone else's view on this, but in general I'd say that if you know what you want and know how to buy it, the government bond ETF becomes a lot less relevant as the liquidity offered (including the actual \"\"ease of transacting\"\") seem to to be the biggest factors in favor. From Investopedia's description: The bond ETF is an exciting new addition to the bond market, offering an excellent alternative to self-directed investors who, looking for ease of trading and increased price transparency, want to practice indexing or active bond trading. However, bond ETFs are suitable for particular strategies. If, for instance, you are looking to create a specific income stream, bond ETFs may not be for you. Be sure to compare your alternatives before investing.\"",
"title": ""
},
{
"docid": "260984",
"text": "There are a few other factors possible here: Taxes - Something you don't mention is what are the tax rates on each of those choices. If the 4% gain is taxed at 33% while the 3% government bond is taxed at 0% then it may well make more sense to have the government bond that makes more money after taxes. Potential changes in rates - Could that 4% rate change at any time? Yield curves are an idea here to consider where at times they can become inverted where short-term bonds yield more than long-term bonds due to expectations about rates. Some banks may advertise a special rate for a limited time to try to get more deposits and then change the rate later. Beware the fine print. Could the bond have some kind of extra feature on it? For example, in the US there are bonds known as TIPS that while the interest rate may be low, there is a principal adjustment that comes as part of the inflation adjustment that is part how the security is structured.",
"title": ""
},
{
"docid": "411966",
"text": "\"The most fundamental observation of bond pricing is this: Bond price is inversely proportional to bond yields When bond yields rise, the price of the bond falls. When bond yields fall, the price of the bond rises. Higher rates are \"\"bad\"\" for bonds. If a selloff occurs in the Russian government bond space (i.e. prices are going down), the yield on that bond is going to increase as a consequence.\"",
"title": ""
},
{
"docid": "538898",
"text": "The Fed sets the overnight borrowing costs by setting its overnight target rate. The markets determine the rates at which the treasury can borrow through the issuance of bonds. The Fed's actions will certainly influence the price of very short term bonds, but the Fed's influence on anything other than very short term bonds in the current environment is very muted. Currently, the most influential factor keeping bond prices high and yields low is the high demand for US treasuries coming from overseas governments and institutions. This is being caused by two factors : sluggish growth in overseas economies and the ongoing strength of the US dollar. With many European government bonds offering negative redemption yields, income investors see US yields as relatively attractive. Those non-US economies which do not have negative bond yields either have near zero yields or large currency risks or both. Political issues such as the survival of the Euro also weigh heavily on market perceptions of the current attractiveness of the US dollar. Italian banks may be about to deliver a shock to the Eurozone, and the Spanish and French banks may not be far behind. Another factor is the continued threat of deflation. Growth is slowing around the world which negatively effects demand. Commodity prices remain depressed. Low growth and recession outside of the US translate into a prolonged period of near zero interest rates elsewhere together with renewed QE programmes in Europe, Japan, and possibly elsewhere. This makes the US look relatively attractive and so there is huge demand for US dollars and bonds. Any significant move in US interest rates risks driving to dollar ever higher which would be very negative for the future earning of US companies which rely on exports and foreign income. All of this makes the market believe that the Fed's hands are tied and low bond yields are here for the foreseeable future. Of course, even in the US growth is relatively slow and vulnerable to a loss of steam following a move in interest rates.",
"title": ""
},
{
"docid": "587032",
"text": "\"The simple answer is that, even though mortgages can go for 10, 15, 20 and 30 year terms in the U.S., they're typically backed by bonds sold to investors that mature in 10 years, which is the standard term for most bonds. These bonds, in the open market, are compared by investors with the 10-year Treasury note, which is the gold standard for low-risk investment; the U.S. Government has a solid history of always paying its bills (though this reputation is being tested in recent years with fights over the debt ceiling and government budgets). The savvy investor, therefore, knows that he or she can make at least the yield from the 10-year T-note in that time frame, with virtually zero risk. Anything else on the market is seen as being a higher risk, and so investors demand higher yields (by making lower bids, forcing the issuer to issue more bonds to get the money it needs up front). Mortgage-backed securities are usually in the next tier above T-debt in terms of risk; when backed by prime-rate mortgages they're typically AAA-rated, making them available to \"\"institutional investors\"\" like banks, mutual funds, etc. This forms a balancing act; mortgage-backed securities issuers typically can't get the yield of a T-note, because no matter how low their risk, T-debt is lower (because one bank doesn't have the power to tax the entire U.S. population). But, they're almost as good because they're still very stable, low-risk debt. This bond price, and the resulting yield, is in turn the baseline for a long-term loan by the bank to an individual. The bank, watching the market and its other bond packages, knows what it can get for a package of bonds backed by your mortgage (and others with similar credit scores). It will therefore take this number, add a couple of percentage points to make some money for itself and its stockholders (how much the bank can add is tacitly controlled by other market forces; you're allowed to shop around for the lowest rate you can get, which limits any one bank's ability to jack up rates), and this is the rate you see advertised and - hopefully - what shows up on your paperwork after you apply.\"",
"title": ""
},
{
"docid": "495600",
"text": "\"Question 1: How do I start? or \"\"the broker\"\" problem Get an online broker. You can do a wire transfer to fund the account from your bank. Question 2: What criticism do you have for my plan? Dividend investing is smart. The only problem is that everyone's currently doing it. There is an insatiable demand for yield, not just individual investors but investment firms and pension funds that need to generate income to fund retirements for their clients. As more investors purchase the shares of dividend paying securities, the share price goes up. As the share price goes up, the dividend yield goes down. Same for bonds. For example, if a stock pays $1 per year in dividends, and you purchase the shares at $20/each, then your yearly return (not including share price fluctuations) would be 1/20 = 5%. But if you end up having to pay $30 per share, then your yearly return would be 1/30 or 3.3% yield. The more money you invest, the bigger this difference becomes; with $100K invested you'd make about $1.6K more at 5%. (BTW, don't put all your money in any small group of stocks, you want to diversify). ETFs work the same way, where new investors buying the shares cause the custodian to purchase more shares of the underlying securities, thus driving up the price up and yield down. Instead of ETFs, I'd have a look at something called closed end funds, or CEFs which also hold an underlying basket of securities but often trade at a discount to their net asset value, unlike ETFs. CEFs usually have higher yields than their ETF counterparts. I can't fully describe the ins and outs here in this space, but you'll definately want to do some research on them to better understand what you're buying, and HOW to successfully buy (ie make sure you're buying at a historically steep discount to NAV [https://seekingalpha.com/article/1116411-the-closed-end-fund-trifecta-how-to-analyze-a-cef] and where to screen [https://www.cefconnect.com/closed-end-funds-screener] Regardless of whether you decide to buy stocks, bonds, ETFs, CEFs, sell puts, or some mix, the best advice I can give is to a) diversify (personally, with a single RARE exception, I never let any one holding account for more than 2% of my total portfolio value), and b) space out your purchases over time. b) is important because we've been in a low interest rate environment since about 2009, and when the risk free rate of return is very low, investors purchase stocks and bonds which results in lower yields. As the risk free rate of return is expected to finally start slowly rising in 2017 and gradually over time, there should be gradual downward pressure (ie selling) on the prices of dividend stocks and especially bonds meaning you'll get better yields if you wait. Then again, we could hit a recession and the central banks actually lower rates which is why I say you want to space your purchases out.\"",
"title": ""
},
{
"docid": "239271",
"text": "Big money, by vitue of its own existence, produces value. What's a person to do with it? Stuff it under a mattress and earn 0 yield? No. If you want safety, you'll put it in AAA rated US gov't bonds and help fund the government. If you want yield, you'll put it in broadly diversified equities investments, small companies, big companies, energy companies, tech companies, media companies, and so on, and soak up the net gain while injecting much needed capital investment directly into those industries, financing start up costs like construction and equipment procurement costs, as well as staffing costs. Yes, big money absolutely creates value. The trains, cars, roads, and sidewalks you travel through to get to work? All financed by filthy rich people money. The building you work in and the equipment you use? Likely financed by filthy rich people money as well. Its called financial intermediation and capital arbitrage, and you can thank your Gods you live in a country where the government allows it to operate efficiently.",
"title": ""
},
{
"docid": "215189",
"text": "\"All of the other answers here are accurate, but (I think) are missing the point as to the question, which rests on how Bonds work in the first place. The bond specifies a payback AMOUNT and DATE. Let's say it is $10,000 and one year from today. If you buy that today for $9900, your yield will be 1%. If you buy it today for $11,000, your yield will be less than 0% (please don't make me do the math - it's just under negative 1%). You might be willing to pay that 1% (rather than receive 1%) for the certainty that you will definitely get your money back. The combined actions of all the people who may be willing to pay a little more or a little less for the safety of a US Treasury Bond is what people call \"\"the Market.\"\" Market forces (generally, investor confidence) will drive the price up and down, which affects the yield. All the other stuff - coupons and inflation and whatnot - all of that only makes sense if you understand that you aren't buying a rate of return, you are buying a payback amount and date.\"",
"title": ""
},
{
"docid": "97729",
"text": "You can look at TIPS (which have some inflation protection built in). Generally short term bonds are better than long if you expect rates to rise soon. Other ways that you can protect yourself are to choose higher yield corporate bonds instead of government bonds, or to use foreign bonds. There are plenty of bond funds like Templeton Global or ETFs that offer such features. Find one that will work for you.",
"title": ""
},
{
"docid": "227433",
"text": "\"Why does the yield go up if the country is economically unstable? The yield will rise when instability increases because the risk of default increases. If the case of Greece, the instability of government finances resulted in a 50% \"\"haircut\"\" for bond holders in 2011. In other words, bond holders suffered a 50% write down in the nominal value of their bonds. This means that holding these bonds until maturity will mean they will only receive half of the original nominal value of the bond, and that is assuming no further write downs occur. Why does selling a bond drive up the yield? Significant selling of bonds means that sellers are worried about future prospects. Sellers will outnumber buyers, so sellers will have to reduce their offer price in order to attract new buyers. So if you think Greece is not going to default as it's highly likely a country would completely default, wouldn't it make sense to hold onto the bonds? If you think that it is highly unlikely that Greece will default and the prices and yields are attractive, then Greek bonds may look like an attractive investment. However, keep in mind the fate of bond holders in 2011. They were attracted to Greek bonds by the price and yield, but they suffered a 50% haircut.\"",
"title": ""
},
{
"docid": "269550",
"text": "Buy a fund of bonds, there are plenty and are registered on your stockbroker account as 'funds' rather than shares. Otherwise, to the individual investor, they can be considered as the same thing. Funds (of bonds, rather than funds that contain property or shares or other investments) are often high yield, low volatility. You buy the fund, and let the manager work it for you. He buys bonds in accordance to the specification of the fund (ie some funds will say 'European only', or 'global high yield' etc) and he will buy and sell the bonds regularly. You never hold to maturity as this is handled for you - in many cases, the manager will be buying and selling bonds all the time in order to give you a stable fund that returns you a dividend. Private investors can buy bonds directly, but its not common. Should you do it? Up to you. Bonds return, the company issuing a corporate bond will do so at a fixed price with a fixed yield. At the end of the term, they return the principal. So a 20-year bond with a 5% yield will return someone who invests £10k, £500 a year and at the end of the 20 years will return the £10k. The corporate doesn't care who holds the bond, so you can happily sell it to someone else, probably for £10km give or take. People say to invest in bonds because they do not move much in value. In financially difficult times, this means bonds are more attractive to investors as they are a safe place to hold money while stocks drop, but in good times the opposite applies, no-one wants a fund returning 5% when they think they can get 20% growth from a stock.",
"title": ""
},
{
"docid": "457122",
"text": "\"For a two year time frame, a good insured savings account or a low-cost short-term government bond fund is most likely the way I would go. Depending on the specific amount, it may also be reasonable to look into directly buying government bonds. The reason for this is simply that in such a short time period, the stock market can be extremely volatile. Imagine if you had gone all in with the money on the stock market in, say, 2007, intending to withdraw the money after two years. Take a broad stock market index of your choice and see how much you'd have got back, and consider if you'd have felt comfortable sticking to your plan for the duration. Since you would likely be focused more on preservation of capital than returns during such a relatively short period, the risk of the stock market making a major (or even relatively minor) downturn in the interim would (should) be a bigger consideration than the possibility of a higher return. The \"\"return of capital, not return on capital\"\" rule. If the stock market falls by 10%, it must go up by 11% to break even. If it falls by 25%, it must go up by 33% to break even. If you are looking at a slightly longer time period, such as the example five years, then you might want to add some stocks to the mix for the possibility of a higher return. Still, however, since you have a specific goal in mind that is still reasonably close in time, I would likely keep a large fraction of the money in interest-bearing holdings (bank account, bonds, bond funds) rather than in the stock market. A good compromise may be medium-to-high-yield corporate bonds. It shouldn't be too difficult to find such bond funds that can return a few percentage points above risk-free interest, if you can live with the price volatility. Over time and as you get closer to actually needing the money, shift the holdings to lower-risk holdings to secure the capital amount. Yes, short-term government bonds tend to have dismal returns, particularly currently. (It's pretty much either that, or the country is just about bankrupt already, which means that the risk of default is quite high which is reflected in the interest premiums demanded by investors.) But the risk in most countries' short-term government bonds is also very much limited. And generally, when you are looking at using the money for a specific purpose within a defined (and relatively short) time frame, you want to reduce risk, even if that comes with the price tag of a slightly lower return. And, as always, never put all your eggs in one basket. A combination of government bonds from various countries may be appropriate, just as you should diversify between different stocks in a well-balanced portfolio. Make sure to check the limits on how much money is insured in a single account, for a single individual, in a single institution and for a household - you don't want to chase high interest bank accounts only to be burned by something like that if the institution goes bankrupt. Generally, the sooner you expect to need the money, the less risk you should take, even if that means a lower return on capital. And the risk progression (ignoring currency effects, which affects all of these equally) is roughly short-term government bonds, long-term government bonds or regular corporate bonds, high-yield corporate bonds, stock market large cap, stock market mid and low cap. Yes, there are exceptions, but that's a resonable rule of thumb.\"",
"title": ""
},
{
"docid": "462668",
"text": "\"This is a hard question to answer. Government debt and mortgages are loosely related. Banks typically use yields on government bonds to determine mortgage interest rates. The banks must be able to get higher rates from the mortgage otherwise they would buy government bonds. Your question mentions default so I'm assuming a country has reneged on its promise to pay either the principal or interest on government bonds. The main thing to consider is \"\"Who does not get their money?\"\". In other words, who does the government decide not to pay. This is the important part. The government will have some money so they could pay some bond holders. They must decide who to shaft. For example, let's look at who holds Greek government debt. Around 70% of Greek government debt is held outside Greece. See table below. The Greek government could decide to default only on the debt to foreign holders. In that case the banks in France and Switzerland would take the loss on their bonds. This could cause severe problems in France and Switzerland depending on the percentage of Greek bonds that make up the banks' assets. Greek banks would still face losses, however, since the price of their Greek bond holdings would drop sharply when the government defaults. Interestingly, the losses for the Greek banks may be smaller than the losses faced by the French and Swiss banks. This is usually the favored option chosen by government since the French and Swiss don't vote in Greece. Yields on Greek government bonds would rise dramatically. If your Greek mortgage is an adjustable rate mortgage then you could see some big adjustments upward. If you live in France or Switzerland then the bank that owns your mortgage may go under if Greece defaults. During liquidation the bank will sell their assets which includes mortgages and you will probably not notice any difference in your mortgage. As I stated earlier: this is a hard question to answer since the two financial instruments involved (bonds and mortgages) are similar but may or may not be related.\"",
"title": ""
},
{
"docid": "237317",
"text": "A large number of bond holders decide to sell their bonds. If they all decide to do this at the same time then there will be a large supply of bonds being sold in the market. This will drive down the price of the bonds which will increase yields. Why do bond yields move inversely to bond prices? You purchase a $100 bond today that yields 5%. You spent $100. The very next day the same bonds are being sold with a yield of 10%. If you wanted to sell your bond to someone you would have to sell it so it competed with the new bonds being sold. You could not sell it for $100 which is what you paid for it. You would have to sell it for less than the $100 you paid for it in order for it to have the equivalent yield of the new bonds being sold with a 10% yield. This is why bond yields move inversely to bond prices. Why does rising yields increase the cost of borrowing? If someone is trying to sell new bonds they will have to sell bonds that compete with the yields of the current bonds already in the market. If yields are rising on the existing bonds then the issuer of the new bonds will have to pay higher interest rates to offer equivalent yields on the new bonds. The issuer is now paying more in interest making it more expensive to borrow money. What are the incentives for the bond vigilante to sell his/her bonds? One reason a bond holder will sell his/her bonds is they believe inflation will outpace the yield on the bond they are holding. If a bond yields 3% and inflation is at 5% then the bond holder is essentially losing purchasing power if they continue to hold onto the bond. Another reason to sell would be if the bond holder has doubts in the ability of the issuer to repay the interest and/or principal of the bond.",
"title": ""
},
{
"docid": "131380",
"text": "Theoretically the yield curve is an expectation of inflation, however in practice (currently) the government yield curve is an expectation of banking fear. As you put your money with the government if you think the bank is going to default. With the FED lowering the longer end and making government less attractive, operation twist should theoretically lower both long term corp bond rates and stop people from buying long gov bonds (crowding out of capital).",
"title": ""
},
{
"docid": "523140",
"text": "G spread - you have a 5.5 year bond, you take your yield minus the yield on the 5.5y point (interpolated) of the benchmark sovereign curve. Think of G = Government. I Spread - same as G Spread but you use the relevant Swap Curve. E.g. USD bond, compare against the USD Swaps curve. I = interpolated. Z Spread - stands for zero volatility curve spread. You strip the swaps curve to get zero rates (i.e. Zero coupon rates for each tenor), then find the constant spread on top of each part of the curve's zero rates to arrive at your bond's yield. In G and I Spread, you're basically discounting the bond's cash flows using one rate (i.e. The interpolated yield on the curve). With Z Spread, you're discounting using the entire portion of the curve that's relevant to your bond's maturity.",
"title": ""
},
{
"docid": "370121",
"text": "I'm going to make an educated guess on #1. Money markets invest in bonds with a very short time to maturity. An MMA at a bank will be invested in government bonds. Yields on these bonds are really low right now. Thus the yield on that MMA is going to be pretty low. When you make a deposit in a savings account, the bank uses some of that money to lend back out to its customers in the form of car loans, mortgages, etc. These rates are higher, so the bank is willing to pay you a bit more than the yield MMA so they can use your money for these loans. For #2, your time window is short, so there aren't really a lot of options for you. Keeping your money where it is will actually cost you money in fees. You can do as I suggested in my comment above: close the current savings account that's hitting you with fees and open a (free) high yield savings account. You might get 1.1%. If you average $60k in the account over the next 6 months you'll earn $200-250 after taxes. You didn't ask about CDs, but lately shorter term CDs are paying less than savings accounts. Going out to a year will get you just above the rate on a high yield savings account; two years just a little more. These are outside your goal window, so they aren't an option for you.",
"title": ""
},
{
"docid": "4180",
"text": "\"I don't understand the worker mentality of accepting to be part of pension plans. The downside risk to you is ridiculously high -- you're basically making an investment that the next 30 years of corporate management and the company as a whole are going to be good. Pension plans are among the first to go.. employees that retired 20-30 years ago add no current value to the company, unless you consider that current employees are motivated by the idea of a pension or working for a company that \"\"takes care\"\" of its employees. Also, part of the reason pension funds are blowing up is that the risk-free return rate is less than 1%. I don't know who to blame or thank for that, but with government bonds now trading at negative yields in real and sometimes even absolute terms (see: Swiss yields), what else are you supposed to do?\"",
"title": ""
},
{
"docid": "462697",
"text": "\"that would imply that a 30Y US Treasury bond only yields 2.78%, which is nonsensically low. Those are annualized yields. It would be more precise to say that \"\"a 30Y US Treasury bond yields 2.78% per year (annualized) over 30 years\"\", but that terminology is implied in bond markets. So if you invest $1,000 in a 30-year T-bond, you will earn roughly 2.78% in interest per year. Also note that yield is calculated as if it compounded, meaning that investing in a 30-year T-bind will give you a return that is equivalent to putting it in a savings account that earns 1.39% interest (half of 2.78%) every 6 months and compounds, meaning you earn interest on top of interest. The trade-off for these low yields is you have virtually no default risk. Unlike a company that could go bankrupt and not pay back the bond, the US Government is virtually certain to pay off these bonds because it can print or borrow more money to pay off the debts. In addition, bonds in general (and especially treasuries) have very low market risk, meaning that their value fluctuates much less that equities, even indicies. S&P 500 indices may move anywhere between -40% and 50% in any given year, while T-bonds' range of movement is much lower, between -10% and 30% historically).\"",
"title": ""
},
{
"docid": "175819",
"text": "Your question asked about a specific time the yield curve flattened or inverted. There are other times when the yield curve inverted or flattened. You also imply in your question that investors were flocking to long term bonds which lowered their yields. I don't believe this is the case. I believe investors were fleeing from short term bonds causing the yields on short term bonds to rise to meet those of long term bonds. The chart below shows the history of yields on US bonds over time. The shaded areas are where the yield curve flattened or inverted. Notice that after 1982 it is the short term yields that rise sharply to meet or cross the yields on longer term bonds. The yields on longer term bonds move little compared to the movement in yields on the short term bonds. Thus it is investors moving out of short term bonds that cause the yield curve to flatten or invert. These investors are not moving into longer term bonds since the yields on the longer term bonds do not move much at all at these times. In fact, in 2006 the longer term bond market was only 25% of the total US public debt while short term bonds made up 75%. It would take less money to move the yields on longer term bonds than it would on short term bonds yet the longer term yields did not move near as much as short term yields. So why are investors or banks moving out of short term bonds causing their yields to rise? I believe this happens for one of two reasons: they are moving into higher yielding investments or they need to raise cash to cover bad investments. Charts and more information here.",
"title": ""
},
{
"docid": "136515",
"text": "\"Bonds still definitely have a place in many passive portfolios. While it is true that interest rates have been unusually low, yields on reasonable passive bond exposures are still around 2-4%. This is significantly better than both recent past inflation and expected inflation both of which are near zero. This is reasonable if not great return, but Bonds continue to have other nice properties like relatively low risk and diversification of stock portfolios (the \"\"offset[ing] losses\"\" you mention in the OP). So to say that bonds are \"\"no longer a good idea\"\" is certainly not correct. One could say bonds may no longer be a good idea for some people that have a particularly high risk tolerance and very high return requirements. However, to some extent, that has always been true. It is worth remembering also that there is some compelling evidence that global growth is starting to broadly slow down and many people believe that future stock returns and, in general, returns on all investments will be lower. This is much much harder to estimate than bond returns though. Depending on who you believe, bond returns may actually look relatively better than the have in the past. Edit in response to comment: Corporate bond correlation with stocks is positive but generally not very strong (except for high-yield junk bonds) so while they don't offset stock volatility (negative correlation) they do help diversify a stock portfolio. Government bonds have essentially zero correlation so they don't really offset volatility as much as just not add any. Negative correlation assets are generally called insurance and you tend to have to pay for them. So there is no free lunch here. Assets that reduce risk cost money, assets that add little risk give less return and assets that are more risky tend to give more return in the long run but you can feel the pain. The mix that is right for you depends on a lot of things, but for many people that mix involves some corporate and government bonds.\"",
"title": ""
}
] |
178
|
Birth-weight is negatively associated with breast cancer.
|
[
{
"docid": "16322674",
"text": "BACKGROUND Birth size, perhaps a proxy for prenatal environment, might be a correlate of subsequent breast cancer risk, but findings from epidemiological studies have been inconsistent. We re-analysed individual participant data from published and unpublished studies to obtain more precise estimates of the magnitude and shape of the birth size-breast cancer association. METHODS AND FINDINGS Studies were identified through computer-assisted and manual searches, and personal communication with investigators. Individual participant data from 32 studies, comprising 22,058 breast cancer cases, were obtained. Random effect models were used, if appropriate, to combine study-specific estimates of effect. Birth weight was positively associated with breast cancer risk in studies based on birth records (pooled relative risk [RR] per one standard deviation [SD] [= 0.5 kg] increment in birth weight: 1.06; 95% confidence interval [CI] 1.02-1.09) and parental recall when the participants were children (1.02; 95% CI 0.99-1.05), but not in those based on adult self-reports, or maternal recall during the woman's adulthood (0.98; 95% CI 0.95-1.01) (p for heterogeneity between data sources = 0.003). Relative to women who weighed 3.000-3.499 kg, the risk was 0.96 (CI 0.80-1.16) in those who weighed < 2.500 kg, and 1.12 (95% CI 1.00-1.25) in those who weighed > or = 4.000 kg (p for linear trend = 0.001) in birth record data. Birth length and head circumference from birth records were also positively associated with breast cancer risk (pooled RR per one SD increment: 1.06 [95% CI 1.03-1.10] and 1.09 [95% CI 1.03-1.15], respectively). Simultaneous adjustment for these three birth size variables showed that length was the strongest independent predictor of risk. The birth size effects did not appear to be confounded or mediated by established breast cancer risk factors and were not modified by age or menopausal status. The cumulative incidence of breast cancer per 100 women by age 80 y in the study populations was estimated to be 10.0, 10.0, 10.4, and 11.5 in those who were, respectively, in the bottom, second, third, and top fourths of the birth length distribution. CONCLUSIONS This pooled analysis of individual participant data is consistent with birth size, and in particular birth length, being an independent correlate of breast cancer risk in adulthood.",
"title": "Birth Size and Breast Cancer Risk: Re-analysis of Individual Participant Data from 32 Studies"
},
{
"docid": "23557241",
"text": "BACKGROUND Emerging evidence suggests an association between female prenatal experience and her subsequent risk of developing breast cancer. Potential underlying mechanisms include variation in amounts of maternal endogenous sex hormones and growth hormones, germ-cell mutations, formation of cancer stem-cells, and other genetic or epigenetic events. We reviewed and summarised quantitatively the available data on intrauterine exposures and risk of breast cancer. METHODS We systematically searched for studies that assessed association between perinatal factors and risk of breast cancer. We reviewed separately each of the perinatal factors, including birthweight, birth length, parental age at delivery, gestational age, intrauterine exposure to diethylstilbestrol, twin membership, maternal pre-eclampsia or eclampsia, and other factors. FINDINGS We identified 57 studies published between Oct 1, 1980, and June 21, 2007. Increased risk of breast cancer was noted with increased birthweight (relative risk [RR] 1.15 [95% CI 1.09-1.21]), birth length (1.28 [1.11-1.48]), higher maternal age (1.13 [1.02-1.25]), and paternal age (1.12 [1.05-1.19]). Decreased risk of breast cancer was noted for maternal pre-eclampsia and eclampsia (0.48 [0.30-0.78]) and twin membership (0.93 [0.87-1.00]). No association was noted between risk of breast cancer and gestational age at birth (0.95 [0.71-1.26]) or maternal diethylstilbestrol treatment (1.40 [0.86-2.28]). INTERPRETATION The intrauterine environment contributes to the predisposition of women to breast cancer in adulthood. The in-utero mechanisms responsible for such predisposition need to be elucidated.",
"title": "Intrauterine factors and risk of breast cancer: a systematic review and meta-analysis of current evidence."
},
{
"docid": "17450673",
"text": "INTRODUCTION Various perinatal factors, including birth weight, birth order, maternal age, gestational age, twin status, and parental smoking, have been postulated to affect breast cancer risk in daughters by altering the hormonal environment of the developing fetal mammary glands. Despite ample biologic plausibility, epidemiologic studies to date have yielded conflicting results. We investigated the associations between perinatal factors and subsequent breast cancer risk through meta-analyses. METHODS We reviewed breast cancer studies published from January 1966 to February 2007 that included data on birth weight, birth order, maternal age, gestational age, twin status, and maternal or paternal smoking. Meta-analyses using random effect models were employed to summarize the results. RESULTS We found that heavier birth weights were associated with increased breast cancer risk, with studies involving five categories of birth weight identifying odds ratios (ORs) of 1.24 (95% confidence interval [CI] 1.04 to 1.48) for 4,000 g or more and 1.15 (95% CI 1.04 to 1.26) for 3,500 g to 3,999 g, relative to a birth weight of 2,500 to 2,599 g. These studies provided no support for a J-shaped relationship of birthweight to risk. Support for an association with birthweight was also derived from studies based on three birth weight categories (OR 1.15 [95% CI 1.01 to 1.31] for > or =4,000 g relative to <3,000 g) and two birth weight categories (OR 1.09 [95% CI 1.02 to 1.18] for > or =3,000 g relative to <3,000 g). Women born to older mothers and twins were also at some increased risk, but the results were heterogeneous across studies and publication years. Birth order, prematurity, and maternal smoking were unrelated to breast cancer risk. CONCLUSION Our findings provide some support for the hypothesis that in utero exposures reflective of higher endogenous hormone levels could affect risk for development of breast cancer in adulthood.",
"title": "Intrauterine environments and breast cancer risk: meta-analysis and systematic review"
},
{
"docid": "27123743",
"text": "Breast cancer may originate in utero. We reviewed the available evidence on the association between birthweight and the risk of breast cancer. To date, 26 research papers addressing this issue have been published. The majority of studies identified a positive link between birthweight and premenopausal, but not postmenopausal, breast cancer. The relative risk estimate for breast cancer comparing women with high birthweight to women with low birthweight combining all studies including both pre- and postmenopausal breast cancer was 1.23 (95% confidence interval 1.13-1.34). The mechanisms underlying this association likely include elevated levels of growth factors that may increase the number of susceptible stem cells in the mammary gland or initiate tumors through DNA mutations. Loss of imprinting (LOI) of growth hormone genes relevant for intrauterine growth, such as insulin-like growth factor 2 (IGF2), leads to abnormally high levels of these hormones evidenced by high birthweight. LOI of IGF2 has also been found in mammary tumor tissue. The role of environmental factors that stimulate such epigenetic regulation of gene expression remains to be elucidated.",
"title": "Role of birthweight in the etiology of breast cancer."
}
] |
[
{
"docid": "37480103",
"text": "CONTEXT During pregnancy, serum levels of estrogen, progesterone, and other hormones are markedly higher than during other periods of life. Pregnancy hormones primarily are produced in the placenta, and signs of placental impairment may serve as indirect markers of hormone exposures during pregnancy. During pregnancy, these markers have been inconsistently associated with subsequent risk of breast cancer in the mother. OBJECTIVE To examine associations between indirect markers of hormonal exposures, such as placental weight and other pregnancy characteristics, and maternal risk of developing breast cancer. DESIGN AND SETTING Population-based cohort study using data from the Swedish Birth Register, the Swedish Cancer Register, the Swedish Cause of Death Register, and the Swedish Register of Population and Population Changes. PARTICIPANTS Women included in the Sweden Birth Register who delivered singletons between 1982 and 1989, with complete information on date of birth and gestational age. Women were followed up until the occurrence of breast cancer, death, or end of follow-up (December 31, 2001). Cox proportional hazards models were used to estimate associations between hormone exposures and risks of breast cancer. MAIN OUTCOME MEASURE Incidence of invasive breast cancer. RESULTS Of 314,019 women in the cohort, 2216 (0.7%) developed breast cancer during the follow-up through 2001, of whom 2100 (95%) were diagnosed before age 50 years. Compared with women who had placentas weighing less than 500 g in 2 consecutive pregnancies, the risk of breast cancer was increased among women whose placentas weighed between 500 and 699 g in their first pregnancy and at least 700 g in their second pregnancy (or vice versa) (adjusted hazard ratio, 1.82; 95% confidence interval [CI], 1.07-3.08), and the corresponding risk was doubled among women whose placentas weighed at least 700 g in both pregnancies (adjusted hazard ratio, 2.05; 95% CI, 1.15-3.64). A high birth weight (> or =4000 g) in 2 successive births was associated with an increased risk of breast cancer before but not after adjusting for placental weight and other covariates (adjusted hazard ratio, 1.10; 95% CI, 0.76-1.59). CONCLUSIONS Placental weight is positively associated with maternal risk of breast cancer. These results further support the hypothesis that pregnancy hormones are important modifiers of subsequent maternal breast cancer risk.",
"title": "Pregnancy characteristics and maternal risk of breast cancer."
},
{
"docid": "5487448",
"text": "Birth weight is a significant predictor of breast cancer risk in adult life and mammary gland mass could be an intermediate stage in this long process. We have studied the association of birth size measurements with mammographic density, a marker of mammary gland mass. For a population-based sample of 893 postmenopausal women without previous cancer in Sweden, we retrieved information on birth size from birth records and their most recent mammography. Film mammograms of the medio-lateral oblique view were digitized and the Cumulus software was used for computer-assisted semi-automated thresholding of mammographic density. Results were analyzed using generalized linear models controlling for possible confounders. Mean percent mammographic density increased when comparing the extreme categories of birth weight (from 15.6% to 18.6%) and head circumference (from 15.5% to 20.4%), and the corresponding linear trends were statistically significant (p values 0.02 and 0.007, respectively). The associations were particularly strong when the cutoff for high versus low mammographic density was set at the relatively high value of 50%. Compared to women weighing 3001-3500 grams at birth, women with birth weights >4000g were at almost 3-fold risk of developing high mammographic density (odds ratio: 2.9, 95% confidence interval 1.1 to 7.9). No association with mammographic density was evident with respect to birth length which, however, is known to be less accurately measured. These results indicate that adult breast density, a powerful predictor of breast cancer risk, has intrauterine roots, as reflected in birth size.",
"title": "Birth weight and mammographic density among postmenopausal women in Sweden."
},
{
"docid": "38784540",
"text": "Objective To determine whether risk factors in childhood and early adulthood affect later mammographic breast density. Methods: Subjects were 628 women who attended a medical examination at the University of Glasgow Student Health Service (1948–1968), responded to a questionnaire (2001) and had a screening mammogram in Scotland (1989–2002). Mammograms (median age of 59years) were classified using a six category classification (SCC) of breast density percent. Logistic regression was used to determine associations between risk factors and having a high-risk mammogram (≥25 dense). Results: In multi-variable analyses, high-risk mammograms were associated with parity (adjusted odds ratio (OR) per child: 0.77 (95 confidence interval (CI) 0.61–0.99)), age at first birth, OR per year: 1.05 (0.99–1.11), smoking at university, OR smokers versus non-smokers: 0.58 (0.36–0.92) and body mass index (BMI) while at university, OR per 1kg/m20.75 (0.69–0.82). No associations with SCC were found for age at menarche, birth weight, oral contraceptive (OC) use, height, leg length or exercise at age 20. Conclusions: We confirm previous findings that breast density is affected by reproductive events and some anthropometric measures, however most of the risk factors acting throughout the life course which we examined were not closely related to adult breast density.",
"title": "Life course breast cancer risk factors and adult breast density (United Kingdom)"
},
{
"docid": "22007333",
"text": "Menstrual and reproductive factors may increase breast cancer risk through a pathway that includes increased mammographic density. We assessed whether known or suspected menstrual and reproductive breast cancer risk factors were cross-sectionally associated with mammographic density, by measuring area of radiographic density and total breast area on mammograms from 801 participants in the Study of Women’s Health Across the Nation (SWAN), a multi-ethnic cohort of pre- and early perimenopausal women. From multivariable linear regression, the following menstrual or reproductive factors were independently associated with percent mammographic density (area of dense breast/breast area): older age at menarche (β = 10.3, P < 0.01, for >13 vs. <12 years), premenstrual cravings and bloating (β = −3.36, P = 0.02), younger age at first full-term birth (β = −8.12, P < 0.01 for ≤23 years versus no births), greater number of births (β = −6.80, P < 0.01 for ≥3 births versus no births), and premenopausal status (β = 3.78, P < 0.01 versus early perimenopausal). Only number of births remained associated with percent density after adjustment for age, race/ethnicity, study site, body mass index (BMI), and smoking. In addition, stratified analyses revealed that the association with number of births was confined to women within the lowest BMI tertile (β = −12.2, P < 0.01 for ≥3 births versus no births). Our data support a mechanism for parity and breast cancer that involves mammographic density among pre- and early perimenopausal women that may be modified by body size.",
"title": "Menstrual and reproductive factors in relation to mammographic density: the Study of Women’s Health Across the Nation (SWAN)"
},
{
"docid": "13765757",
"text": "Ages at menarche and first birth are established risk factors for breast cancer. The interval between these ages may also affect risk, since the breast is more susceptible to carcinogenic insults during this period than during the parous period. However, few investigators have studied this relation. Using logistic regression, the authors evaluated associations between the timing of reproductive events and breast cancer risk among 4,013 cases and 4,069 controls enrolled in a multicenter, population-based US case-control study of White and African-American women (1994-1998). For White, parous premenopausal and postmenopausal women, those who had an interval of > or =16 years between the ages of menarche and first birth had 1.5-fold (95% confidence interval (CI): 1.0, 2.2) and 1.4-fold (95% CI: 1.1, 1.8) increased risks of breast cancer, respectively, in comparison with those who had < or =5 years between these ages. Adjusting for age at first birth altered these risk estimates somewhat, to odds ratios of 1.5 (95% CI: 0.8, 2.9) and 1.0 (95% CI: 0.6, 1.5), respectively. These associations were stronger for lobular and hormone-receptor-positive tumors but were absent among premenopausal African-American women. The authors conclude that the interval between age at menarche and age at first birth is associated with the risk of hormonally sensitive types of breast cancer, particularly among White women.",
"title": "Timing of menarche and first full-term birth in relation to breast cancer risk."
},
{
"docid": "16098747",
"text": "Evaluate known breast cancer risk factors in relation to breast density. We examined factors in relation to breast density in 144,018 New Hampshire (NH) women with at least one mammogram recorded in a statewide mammography registry. Mammographic breast density was measured by radiologists using the BI-RADS classification; risk factors of interest were obtained from patient intake forms and questionnaires. Initial analyses showed a strong inverse influence of age and body mass index (BMI) on breast density. In addition, women with late age at menarche, late age at first birth, premenopausal women, and those currently using hormone therapy (HT) tended to have higher breast density, while those with greater parity tended to have less dense breasts. Analyses stratified on age and BMI suggested interactions, which were formally assessed in a multivariable model. The impact of current HT use, relative to nonuse, differed across age groups, with an inverse association in younger women, and a positive association in older women (p < 0.0001 for the interaction). The positive effects of age at menarche and age at first birth, and the inverse influence of parity were less apparent in women with low BMI than in those with high BMI (p = 0.04, p < 0.0001 and p = 0.01, respectively, for the interactions). We also noted stronger positive effects for age at first birth in postmenopausal women (p = 0.004 for the interaction). The multivariable model indicated a slight positive influence of family history of breast cancer. The influence of age at menarche and reproductive factors on breast density is less evident in women with high BMI. Density is reduced in young women using HT, but increased in HT users of age 50 or more.",
"title": "Breast cancer risk factors in relation to breast density (United States)"
},
{
"docid": "13831842",
"text": "The association between anthropometric indices and the risk of breast cancer was analyzed using pooled data from seven prospective cohort studies. Together, these cohorts comprise 337,819 women and 4,385 incident invasive breast cancer cases. In multivariate analyses controlling for reproductive, dietary, and other risk factors, the pooled relative risk (RR) of breast cancer per height increment of 5 cm was 1.02 (95% confidence interval (CI): 0.96, 1.10) in premenopausal women and 1.07 (95% CI: 1.03, 1.12) in postmenopausal women. Body mass index (BMI) showed significant inverse and positive associations with breast cancer among pre- and postmenopausal women, respectively; these associations were nonlinear. Compared with premenopausal women with a BMI of less than 21 kg/m2, women with a BMI exceeding 31 kg/m2 had an RR of 0.54 (95% CI: 0.34, 0.85). In postmenopausal women, the RRs did not increase further when BMI exceeded 28 kg/m2; the RR for these women was 1.26 (95% CI: 1.09, 1.46). The authors found little evidence for interaction with other breast cancer risk factors. Their data indicate that height is an independent risk factor for postmenopausal breast cancer; in premenopausal women, this relation is less clear. The association between BMI and breast cancer varies by menopausal status. Weight control may reduce the risk among postmenopausal women.",
"title": "Pooled analysis of prospective cohort studies on height, weight, and breast cancer risk."
},
{
"docid": "3285322",
"text": "PURPOSE Mutations in the BRCA1 and BRCA2 genes confer greater risk of developing breast cancer. We determined whether tumor pathologic features and clinical features differ in patients with and without BRCA mutations. PATIENTS AND METHODS Tumor pathologic features and clinical characteristics were examined in 491 women with breast cancer who underwent genetic testing for BRCA mutations between 1997 and 2006. A retrospective review of medical records was conducted to determine clinical characteristics including ethnicity, age and clinical stage at diagnosis, age at parity, number of full-term pregnancies, use of oral contraceptives and hormone replacement therapy, and BRCA mutation status. Tumor pathology was reviewed to determine histologic type, tumor grade, and estrogen receptor, progesterone receptor, and HER-2/neu status. RESULTS Of the 491 patients with identified breast cancers, 391 patients were BRCA negative, and 86 patients were BRCA positive. Triple-negative breast cancer (ie, those with negative estrogen receptor, progesterone receptor, and HER-2/neu status) was diagnosed in 57.1% of the BRCA1-positive patients, 23.3% of the BRCA2-positive patients, and 13.8% of the BRCA-negative patients. BRCA1 mutation carriers had higher nuclear grade tumors than the other two groups (P < .001). Of the triple-negative cancer patients, BRCA2 mutation carriers were older when diagnosed than BRCA1 mutation carriers and noncarriers (P < .01). CONCLUSION These results suggest that tumors associated with BRCA1 mutations may be divided into two distinct groups, triple-negative and non-triple-negative groups. Future studies should seek to determine whether patients with BRCA1 mutations and triple-negative breast cancer respond to treatment better than BRCA-negative patients with similar tumor pathology.",
"title": "Clinical and pathologic characteristics of patients with BRCA-positive and BRCA-negative breast cancer."
},
{
"docid": "13831558",
"text": "BACKGROUND Extensive mammographic density is associated with an increased risk of breast cancer and makes the detection of cancer by mammography difficult, but the influence of density on risk according to method of cancer detection is unknown. METHODS We carried out three nested case-control studies in screened populations with 1112 matched case-control pairs. We examined the association of the measured percentage of density in the baseline mammogram with risk of breast cancer, according to method of cancer detection, time since the initiation of screening, and age. RESULTS As compared with women with density in less than 10% of the mammogram, women with density in 75% or more had an increased risk of breast cancer (odds ratio, 4.7; 95% confidence interval [CI], 3.0 to 7.4), whether detected by screening (odds ratio, 3.5; 95% CI, 2.0 to 6.2) or less than 12 months after a negative screening examination (odds ratio, 17.8; 95% CI, 4.8 to 65.9). Increased risk of breast cancer, whether detected by screening or other means, persisted for at least 8 years after study entry and was greater in younger than in older women. For women younger than the median age of 56 years, 26% of all breast cancers and 50% of cancers detected less than 12 months after a negative screening test were attributable to density in 50% or more of the mammogram. CONCLUSIONS Extensive mammographic density is strongly associated with the risk of breast cancer detected by screening or between screening tests. A substantial fraction of breast cancers can be attributed to this risk factor.",
"title": "Mammographic density and the risk and detection of breast cancer."
},
{
"docid": "313403",
"text": "The tumor microenvironment is composed of tumor cells, fibroblasts, endothelial cells and infiltrating immune cells, which may inhibit or promote tumor growth and progression. The objectives of this retrospective study were to characterize the density of tumor-associated macrophages (TAMs) in breast cancer, and to correlate the density of TAMs with clinicopathological parameters. Paraffin-embedded specimens and clinicopathological data, including up to 5 years follow-up information, were obtained from 172 breast cancer patients. Immunohistochemical staining for CD68 (marker for macrophages) was performed and evaluated in a blinded fashion. We found that TAMs were significantly frequent in high histopathological grade breast cancer patients. Breast cancer patients with a high density of TAMs had significantly lower rates of disease-free survival and 5-year overall survival than patients with low density of TAMs. Furthermore, high-infiltration of TAMs indicated worse survival rate for patients with node-negative breast cancer. In conclusion, the number of TAMs in the tumor stroma is an independent predictor of survival time for breast cancer patients. High-infiltration of TAMs is a significant unfavorable prognostic factor for patients with invasive breast cancer and, as such, is a potentially useful prognostic marker for breast cancer.",
"title": "High-Infiltration of Tumor-Associated Macrophages Predicts Unfavorable Clinical Outcome for Node-Negative Breast Cancer"
},
{
"docid": "25973484",
"text": "Obesity has a complicated relationship to both breast cancer risk and the clinical behavior of the established disease. In postmenopausal women, particularly the elderly, various measures of obesity have been positively associated with risk. However, before menopause increased body weight is inversely related to breast cancer risk. In both premenopausal and postmenopausal breast cancer, the mechanisms by which body weight and obesity affect risk have been related to estrogenic activity. Obesity has also been related to advanced disease at diagnosis and with a poor prognosis in both premenopausal and postmenopausal breast cancer. Breast cancer in African-American women, considering its relationship to obesity, exhibits some important differences from those described in white women, although the high prevalence of obesity in African-American women may contribute to the relatively poor prognosis compared with white American women. Despite the emphasis on estrogens to explain the effects of obesity on breast cancer, other factors may prove to be equally or more important, particularly as they relate to expression of an aggressive tumor phenotype. Among these, this review serves to stress insulin, insulin-like growth factor-I, and leptin, and their relationship to angiogenesis, and transcriptional factors.",
"title": "Breast cancer and obesity: an update."
},
{
"docid": "1171121",
"text": "A considerable subgroup of patients with early breast cancer does not address benefits of anthracycline based chemotherapy. The aim of this retrospective study was to investigate the effect of microvessel density (MVD) and status of p53 protein on 5-year disease free survival (DFS) in the group of breast cancer patients treated with anthracyclines in adjuvant setting. Correlations between MVD, p53 status and other clinicopathological parameters were also assessed. MVD and p53 status were analyzed immunohistochemically in the group of 172 women with breast cancer in clinical stage T1-2, N1-N2, M0. There were 123 tumors (71.5 %) with lower MVD (≤ 214.8 microvesells/mm(2)) and 49 (28.5 %) with higher MVD (>214.8 microvesells/mm(2)). The proportion of higher MVD tumors significantly increased in N2 (P = 0.000) and in estrogen (P = 0.046) or progesterone receptors (P = 0.029) negative tumors. p53 positivity was indicated in 50 cancers (29.1 %) and was significantly associated with higher grade (P = 0.000), steroid receptors negativity (P = 0.000), cytokeratin5/6 positivity (P = 0.026), topoisomerase IIα overexpression (P = 0.005) and higher proliferation rate (P = 0.001). In univariate analysis, higher MVD (P = 0.016) and p53 negativity (P = 0.023) were significantly related with longer DFS (median follow-up 36 months). In multivariate Cox regression analysis MVD was independently associated with DFS. These data suggest that higher MVD is favourable prognostic factors for early advanced breast cancer patients after adjuvant anthracycline based chemotherapy.",
"title": "Microvessel Density and Status of p53 Protein as Potential Prognostic Factors for Adjuvant Anthracycline Chemotherapy in Retrospective Analysis of Early Breast Cancer Patients Group"
},
{
"docid": "20280410",
"text": "Inherited mutations in the gene BRCA2 predispose carriers to early onset breast cancer, but such mutations account for fewer than 2% of all cases in East Anglia. It is likely that low penetrance alleles explain the greater part of inherited susceptibility to breast cancer; polymorphic variants in strongly predisposing genes, such as BRCA2, are candidates for this role. BRCA2 is thought to be involved in DNA double strand break-repair. Few mice in which Brca2 is truncated survive to birth; of those that do, most are male, smaller than their normal littermates and have high cancer incidence. Here we show that a common human polymorphism (N372H) in exon 10 of BRCA2 confers an increased risk of breast cancer: the HH homozygotes have a 1.31-fold (95% CI, 1.07–1.61) greater risk than the NN group. Moreover, in normal female controls of all ages there is a significant deficiency of homozygotes compared with that expected from Hardy-Weinberg equilibrium, whereas in males there is an excess of homozygotes: the HH group has an estimated fitness of 0.82 in females and 1.38 in males. Therefore, this variant of BRCA2 appears also to affect fetal survival in a sex-dependent manner.",
"title": "A common variant in BRCA2 is associated with both breast cancer risk and prenatal viability"
},
{
"docid": "5222182",
"text": "Understanding which factors influence mammographically dense and nondense areas is important because percent mammographic density adjusted for age is a strong, continuously distributed risk factor for breast cancer, especially when adjusted for weight or body mass index. Using computer-assisted methods, we measured mammographically dense areas for 571 monozygotic and 380 dizygotic Australian and North American twin pairs ages 40 to 70 years. We used a novel regression modeling approach in which each twin's measure of dense and nondense area was regressed against one or both of the twin's and co-twin's covariates. The nature of changes to regression estimates with the inclusion of the twin and/or co-twin's covariates can be evaluated for consistency with causal and/or other models. By causal, we mean that if it were possible to vary a covariate experimentally then the expected value of the outcome measure would change. After adjusting for the individual's weight, the co-twin associations with weight were attenuated, consistent with a causal effect of weight on mammographic measures, which in absolute log cm(2)/kg was thrice stronger for nondense than dense area. After adjusting for weight, later age at menarche, and greater height were associated with greater dense and lesser nondense areas in a manner inconsistent with causality. The associations of dense and nondense areas with parity are consistent with a causal effect and/or within-person confounding. The associations between mammographic density measures and height are consistent with shared early life environmental factors that predispose to both height and percent mammographic density and possibly breast cancer risk.",
"title": "Predictors of mammographic density: insights gained from a novel regression analysis of a twin study."
},
{
"docid": "16701509",
"text": "BACKGROUND The prevalence of metabolic syndrome (obesity, glucose intolerance, low serum high-density lipoprotein cholesterol [HDL-C], high serum triglycerides, hypertension) is high and increasing in parallel with an increasing breast cancer incidence worldwide. HDL-C represents an important aspect of the syndrome, yet its role in breast cancer is still undefined. METHODS In two population-based screening surveys during 1977-1983 and 1985-1987, serum HDL-C was assayed enzymatically among 38,823 Norwegian women aged 17-54 years at entry. Height, weight, blood pressure, serum lipids, fat and energy intake, physical activity, parity, oral contraceptive use, hormone therapy use, alcohol intake, and tobacco use were also assessed. We used Cox proportional hazards modeling to estimate the relative risk (RR) of breast cancer associated with serum HDL-C levels and to adjust for potential confounding variables. We performed stratified analyses to evaluate effect modification by body mass index (BMI) and menopausal status. All statistical tests were two-sided. RESULTS During a median follow-up of 17.2 years, we identified 708 cases of invasive breast cancer. In multivariable analysis, the risk of postmenopausal breast cancer was inversely related to quartile of HDL-C (P(trend) =.02). Among women with HDL-C above 1.64 mmol/L (highest quartile) versus below 1.20 mmol/L (lowest quartile), the relative risk was 0.75 (95% confidence interval [CI] = 0.58 to 0.97). The HDL-C association was confined to women in the heavier subgroup (BMI > or =25 kg/m2), for whom the relative risk of postmenopausal breast cancer in those with HDL-C above 1.64 mmol/L versus below 1.20 mmol/L was 0.43 (95% CI = 0.28 to 0.67; P(trend)<.001; P(interaction) =.001). CONCLUSION Low HDL-C, as part of the metabolic syndrome, is associated with increased postmenopausal breast cancer risk.",
"title": "Serum high-density lipoprotein cholesterol, metabolic profile, and breast cancer risk."
},
{
"docid": "18340282",
"text": "BACKGROUND Information is scarce about the combined effects on breast cancer incidence of low-penetrance genetic susceptibility polymorphisms and environmental factors (reproductive, behavioural, and anthropometric risk factors for breast cancer). To test for evidence of gene-environment interactions, we compared genotypic relative risks for breast cancer across the other risk factors in a large UK prospective study. METHODS We tested gene-environment interactions in 7610 women who developed breast cancer and 10 196 controls without the disease, studying the effects of 12 polymorphisms (FGFR2-rs2981582, TNRC9-rs3803662, 2q35-rs13387042, MAP3K1-rs889312, 8q24-rs13281615, 2p-rs4666451, 5p12-rs981782, CASP8-rs1045485, LSP1-rs3817198, 5q-rs30099, TGFB1-rs1982073, and ATM-rs1800054) in relation to prospectively collected information about ten established environmental risk factors (age at menarche, parity, age at first birth, breastfeeding, menopausal status, age at menopause, use of hormone replacement therapy, body-mass index, height, and alcohol consumption). FINDINGS After allowance for multiple testing none of the 120 comparisons yielded significant evidence of a gene-environment interaction. By contrast with previous suggestions, there was little evidence that the genotypic relative risks were affected by use of hormone replacement therapy, either overall or for oestrogen-receptor-positive disease. Only one of the 12 polymorphisms was correlated with any of the ten other risk factors: carriers of the high-risk C allele of MAP3K1-rs889312 were significantly shorter than non-carriers (mean height 162.4 cm [95% CI 162.1-162.7] vs 163.1 cm [162.9-163.2]; p=0.01 after allowance for multiple testing). INTERPRETATION Risks of breast cancer associated with low-penetrance susceptibility polymorphisms do not vary significantly with these ten established environmental risk factors. FUNDING Cancer Research UK and the UK Medical Research Council.",
"title": "Gene–environment interactions in 7610 women with breast cancer: prospective evidence from the Million Women Study"
},
{
"docid": "27240667",
"text": "PURPOSE Since 1990, overall breast cancer mortality rates in the United States decreased 24%. This decline has been attributed to mammography screening and adjuvant systemic therapy. However, the efficacy of these modalities may depend on estrogen receptor (ER) expression and age. We therefore examined breast cancer mortality trends in the United States according to ER status and age. METHODS Using the Surveillance, Epidemiology, and End Results (SEER) program (1990-2003), we calculated trends in incidence-based mortality (IBM), annual hazard rates for breast cancer deaths after diagnosis, and relative hazard rates for women with ER-positive and ER-negative tumors. Relative hazard rates were assessed with Cox proportional hazards models, adjusted for stage and grade, and stratified by age at diagnosis. RESULTS During the study period, IBM and annual hazard rates for breast cancer deaths decreased among women with ER-positive and ER-negative tumors, although declines were greater for those with ER-positive tumors. Among women younger than 70 years, relative hazard rates declined 38% for those with ER-positive tumors versus 19% for those with ER-negative tumors. Among women 70 years or older, relative hazard rates declined 14% for those with ER-positive tumors versus no significant decline for those with ER-negative tumors. CONCLUSION In the United States, breast cancer mortality rates have declined among women with ER-positive and ER-negative tumors, with greater declines among younger women and those with ER-positive tumors. Although mortality in all groups remains unacceptably high, additional emphasis should be placed on improving outcomes of breast cancer patients older than 70 years and those of all ages with ER-negative tumors.",
"title": "Breast cancer mortality trends in the United States according to estrogen receptor status and age at diagnosis."
},
{
"docid": "12762485",
"text": "AIM Several studies have investigated the expression of the cytokeratins (CKs), vimentin, the epithelial growth factor receptor (EGFR), the oestrogen receptor (ER), and the progesterone receptor (PgR), in breast cancer, but no study has directly compared p53 mutations with these phenotypic and differentiation markers in the same case. The present study was designed to provide some of this information. METHODS The expression of the p53 and bcl-2 proteins was evaluated by immunohistochemistry in relation to phenotypic characteristics and cellular kinetic parameters (mitotic index and apoptotic index) in 37 cases of ductal carcinoma in situ (DCIS) and 27 cases of infiltrating ductal carcinoma (IDC) of the breast. In addition, p53 gene mutation was examined by polymerase chain reaction single strand conformation polymorphism analysis (SSCP). RESULTS Thirteen cases (eight DCIS and five IDC) showed expression of CK8, CK14, CK18, vimentin, and EGFR, consistent with a stem cell phenotype, whereas 44 cases (27 DCIS and 17 IDC) showed expression of CK8 and CK1, weak or negative expression of CK18, but were negative for vimentin and EGFR, consistent with a luminal cell phenotype. DCIS and IDC cases with a stem cell phenotype were ER/PgR negative and intermediately or poorly differentiated. In contrast, the cases with luminal cell phenotype were ER/PgR positive and well or intermediately differentiated. In addition, intermediately or poorly differentiated cases with a stem cell phenotype showed higher proliferative activity (per cent of MIB-l positive cells) than did intermediately or well differentiated cases with a luminal cell phenotype. Both DCIS and IDC cases with a stem cell phenotype were p53 positive and bcl-2 negative by immunohistochemistry. In IDC, p53 expression was associated with a reduction of both mitotic index and apoptotic index compared with DCIS. Most of the tumours showing a more differentiated phenotype (luminal) were p53 negative and bcl-2 positive. In these cases, cell kinetic parameters increased from DCIS to IDC. These data suggest the existence of subsets of DCIS and IDC that, because of their phenotypic characteristics, could be derived from subpopulations of normal breast cells having different control mechanisms of cell proliferation and neoplastic progression. CONCLUSIONS These results are compatible with the hypothesis that the phenotype of the cell of origin constrains both tumour phenotype and the choice of genetic events; however, the occurrence of p53 mutants by chance during neoplastic transformation cannot be excluded.",
"title": "p53 mutation in breast cancer. Correlation with cell kinetics and cell of origin."
},
{
"docid": "4828631",
"text": "BACKGROUND High body-mass index (BMI) predisposes to several site-specific cancers, but a large-scale systematic and detailed characterisation of patterns of risk across all common cancers adjusted for potential confounders has not previously been undertaken. We aimed to investigate the links between BMI and the most common site-specific cancers. METHODS With primary care data from individuals in the Clinical Practice Research Datalink with BMI data, we fitted Cox models to investigate associations between BMI and 22 of the most common cancers, adjusting for potential confounders. We fitted linear then non-linear (spline) models; investigated effect modification by sex, menopausal status, smoking, and age; and calculated population effects. FINDINGS 5·24 million individuals were included; 166,955 developed cancers of interest. BMI was associated with 17 of 22 cancers, but effects varied substantially by site. Each 5 kg/m(2) increase in BMI was roughly linearly associated with cancers of the uterus (hazard ratio [HR] 1·62, 99% CI 1·56-1·69; p<0·0001), gallbladder (1·31, 1·12-1·52; p<0·0001), kidney (1·25, 1·17-1·33; p<0·0001), cervix (1·10, 1·03-1·17; p=0·00035), thyroid (1·09, 1·00-1·19; p=0·0088), and leukaemia (1·09, 1·05-1·13; p≤0·0001). BMI was positively associated with liver (1·19, 1·12-1·27), colon (1·10, 1·07-1·13), ovarian (1·09, 1.04-1.14), and postmenopausal breast cancers (1·05, 1·03-1·07) overall (all p<0·0001), but these effects varied by underlying BMI or individual-level characteristics. We estimated inverse associations with prostate and premenopausal breast cancer risk, both overall (prostate 0·98, 0·95-1·00; premenopausal breast cancer 0·89, 0·86-0·92) and in never-smokers (prostate 0·96, 0·93-0·99; premenopausal breast cancer 0·89, 0·85-0·94). By contrast, for lung and oral cavity cancer, we observed no association in never smokers (lung 0·99, 0·93-1·05; oral cavity 1·07, 0·91-1·26): inverse associations overall were driven by current smokers and ex-smokers, probably because of residual confounding by smoking amount. Assuming causality, 41% of uterine and 10% or more of gallbladder, kidney, liver, and colon cancers could be attributable to excess weight. We estimated that a 1 kg/m(2) population-wide increase in BMI would result in 3790 additional annual UK patients developing one of the ten cancers positively associated with BMI. INTERPRETATION BMI is associated with cancer risk, with substantial population-level effects. The heterogeneity in the effects suggests that different mechanisms are associated with different cancer sites and different patient subgroups. FUNDING National Institute for Health Research, Wellcome Trust, and Medical Research Council.",
"title": "Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5·24 million UK adults"
},
{
"docid": "20839751",
"text": "Apoptosis is a frequent phenomenon in breast cancer and it can be detected by light microscopy in conventional histopathological sections or by special staining techniques. The number of apoptotic cells as a percentage of cells present, or the number of apoptotic cells per square millimetre of neoplastic tissue, is usually described as the apoptotic index (AI). In breast cancer, the AI is not related to tumour size, axillary lymph node metastasis or distant metastasis at diagnosis. It is greater in invasive ductal carcinomas than in other histological types. High AI is also related to high histological grade, high nuclear grade, comedo-type necrosis, lack of tubule formation, and dense infiltration of the tumour by lymphocytes. Sex steroid receptor-negative tumours have greater AIs than the sex steroid receptor-positive ones. Aneuploid breast cancers with high S-phase fractions (SPFs) also have high AI values compared with diploid tumours with low SPFs. p53-Positive breast cancers have high AIs, whereas tumours that are Bcl-2 positive have low AIs. The AI shows a strong positive correlation to all direct or indirect indicators of cell proliferation, such as mitotic index and Ki67 immunolabelling. Univariate survival analyses show that a high AI is linked with unfavourable disease outcome in axillary lymph node-negative and -positive breast cancer, but multivariate analyses indicate that AI is not an independent prognostic factor. In conclusion, a high AI is related to malignant cellular features and indicators of invasiveness and cell proliferation in breast cancer.",
"title": "Apoptosis in breast cancer: relationship with other pathological parameters."
},
{
"docid": "2425364",
"text": "OBJECTIVE To assess the effect of 25-hydroxyvitamin D (25-OHD) levels on pregnancy outcomes and birth variables. DESIGN Systematic review and meta-analysis. DATA SOURCES Medline (1966 to August 2012), PubMed (2008 to August 2012), Embase (1980 to August 2012), CINAHL (1981 to August 2012), the Cochrane database of systematic reviews, and the Cochrane database of registered clinical trials. STUDY SELECTION Studies reporting on the association between serum 25-OHD levels during pregnancy and the outcomes of interest (pre-eclampsia, gestational diabetes, bacterial vaginosis, caesarean section, small for gestational age infants, birth weight, birth length, and head circumference). DATA EXTRACTION Two authors independently extracted data from original research articles, including key indicators of study quality. We pooled the most adjusted odds ratios and weighted mean differences. Associations were tested in subgroups representing different patient characteristics and study quality. RESULTS 3357 studies were identified and reviewed for eligibility. 31 eligible studies were included in the final analysis. Insufficient serum levels of 25-OHD were associated with gestational diabetes (pooled odds ratio 1.49, 95% confidence interval 1.18 to 1.89), pre-eclampsia (1.79, 1.25 to 2.58), and small for gestational age infants (1.85, 1.52 to 2.26). Pregnant women with low serum 25-OHD levels had an increased risk of bacterial vaginosis and low birthweight infants but not delivery by caesarean section. CONCLUSION Vitamin D insufficiency is associated with an increased risk of gestational diabetes, pre-eclampsia, and small for gestational age infants. Pregnant women with low 25-OHD levels had an increased risk of bacterial vaginosis and lower birth weight infants, but not delivery by caesarean section.",
"title": "Association between maternal serum 25-hydroxyvitamin D level and pregnancy and neonatal outcomes: systematic review and meta-analysis of observational studies."
},
{
"docid": "3524352",
"text": "High breast cancer mortality rates have been reported in the northeastern part of the United States, with recent attention focused on Long Island, New York. In this study, the authors investigate whether the high breast cancer mortality is evenly spread over the Northeast, in the sense that any observed clusters of deaths can be explained by chance alone, or whether there are clusters of statistical significance. Demographic data and age-specific breast cancer mortality rates for women were obtained for all 244 counties in 11 northeastern states and for the District of Columbia for 1988-1992. A recently developed spatial scan statistic is used, which searches for clusters of cases without specifying their size or location ahead of time, and which tests for their statistical significance while adjusting for the multiple testing inherent in such a procedure. The basic analysis is adjusted for age, with further analyses examining how the results are affected by incorporating race, urbanicity, and parity as confounding variables. There is a statistically significant and geographically broad cluster of breast cancer deaths in the New York City-Philadelphia, Pennsylvania, metropolitan area (p = 0.0001), which has a 7.4% higher mortality rate than the rest of the Northeast. The cluster remains significant when race, urbanicity, and/or parity are included as confounding variables. Four smaller subclusters within this area are also significant on their own strength: Philadelphia with suburbs (p = 0.0001), Long Island (p = 0.0001), central New Jersey (p = 0.0001), and northeastern New Jersey (p = 0.0001). The elevated breast cancer mortality on Long Island might be viewed less as a unique local phenomenon and more as part of a more general situation involving large parts of the New York City-Philadelphia metropolitan area. The several known and hypothesized risk factors for which we could not adjust and that may explain the detected cluster are most notably age at first birth, age at menarche, age at menopause, breastfeeding, genetic mutations, and environmental factors.",
"title": "Breast cancer clusters in the northeast United States: a geographic analysis."
},
{
"docid": "8529693",
"text": "In this paper we review the associations between maternal and child undernutrition with human capital and risk of adult diseases in low-income and middle-income countries. We analysed data from five long-standing prospective cohort studies from Brazil, Guatemala, India, the Philippines, and South Africa and noted that indices of maternal and child undernutrition (maternal height, birthweight, intrauterine growth restriction, and weight, height, and body-mass index at 2 years according to the new WHO growth standards) were related to adult outcomes (height, schooling, income or assets, offspring birthweight, body-mass index, glucose concentrations, blood pressure). We undertook systematic reviews of studies from low-income and middle-income countries for these outcomes and for indicators related to blood lipids, cardiovascular disease, lung and immune function, cancers, osteoporosis, and mental illness. Undernutrition was strongly associated, both in the review of published work and in new analyses, with shorter adult height, less schooling, reduced economic productivity, and--for women--lower offspring birthweight. Associations with adult disease indicators were not so clear-cut. Increased size at birth and in childhood were positively associated with adult body-mass index and to a lesser extent with blood pressure values, but not with blood glucose concentrations. In our new analyses and in published work, lower birthweight and undernutrition in childhood were risk factors for high glucose concentrations, blood pressure, and harmful lipid profiles once adult body-mass index and height were adjusted for, suggesting that rapid postnatal weight gain--especially after infancy--is linked to these conditions. The review of published works indicates that there is insufficient information about long-term changes in immune function, blood lipids, or osteoporosis indicators. Birthweight is positively associated with lung function and with the incidence of some cancers, and undernutrition could be associated with mental illness. We noted that height-for-age at 2 years was the best predictor of human capital and that undernutrition is associated with lower human capital. We conclude that damage suffered in early life leads to permanent impairment, and might also affect future generations. Its prevention will probably bring about important health, educational, and economic benefits. Chronic diseases are especially common in undernourished children who experience rapid weight gain after infancy.",
"title": "Maternal and child undernutrition: consequences for adult health and human capital"
},
{
"docid": "24249915",
"text": "To gain insights into the possible role of oestrogen receptor (ER) beta in breast carcinogenesis, immunohistochemical analysis of ER beta was performed on 512 breast specimens encompassing normal (n = 138), pure ductal carcinoma in situ (n = 16), invasive cancers (n = 319), lymph node metastases (n = 31), and recurrences (n = 8). Real-time polymerase chain reaction (PCR) was used to investigate the methylation status of the ER beta gene in the ER beta negative breast cancer cell lines SkBr3 and MDA-MB-435. A gradual reduction in, but not a complete loss of, ER beta expression was observed during the transition from normal and pre-invasive lesions to invasive cancers, where ER beta was lost in 21% of cases. This was more pronounced in invasive ductal than in lobular carcinomas, a significantly higher proportion of which were ER beta-positive (74% compared with 91%, respectively, p = 0.0004). Examination of paired primary cancers with their axillary lymph node metastases showed that if ER beta was present in the primary tumour, it persisted in the metastasis. Treatment of ER beta-negative cell lines with DNA methyl transferase inhibitors restored ER beta expression, providing experimental evidence that silencing of ER beta in breast carcinomas could be due to promoter hypermethylation. These results suggest that loss of ER beta expression is one of the hallmarks of breast carcinogenesis and that it may be a reversible process involving methylation.",
"title": "Reduced expression of oestrogen receptor beta in invasive breast cancer and its re-expression using DNA methyl transferase inhibitors in a cell line model."
},
{
"docid": "11360768",
"text": "OBJECTIVE To evaluate the effects of dietary and lifestyle interventions in pregnancy on maternal and fetal weight and to quantify the effects of these interventions on obstetric outcomes. DESIGN Systematic review and meta-analysis. DATA SOURCES Major databases from inception to January 2012 without language restrictions. STUDY SELECTION Randomised controlled trials that evaluated any dietary or lifestyle interventions with potential to influence maternal weight during pregnancy and outcomes of pregnancy. DATA SYNTHESIS Results summarised as relative risks for dichotomous data and mean differences for continuous data. RESULTS We identified 44 relevant randomised controlled trials (7278 women) evaluating three categories of interventions: diet, physical activity, and a mixed approach. Overall, there was 1.42 kg reduction (95% confidence interval 0.95 to 1.89 kg) in gestational weight gain with any intervention compared with control. With all interventions combined, there were no significant differences in birth weight (mean difference -50 g, -100 to 0 g) and the incidence of large for gestational age (relative risk 0.85, 0.66 to 1.09) or small for gestational age (1.00, 0.78 to 1.28) babies between the groups, though by itself physical activity was associated with reduced birth weight (mean difference -60 g, -120 to -10 g). Interventions were associated with a reduced the risk of pre-eclampsia (0.74, 0.60 to 0.92) and shoulder dystocia (0.39, 0.22 to 0.70), with no significant effect on other critically important outcomes. Dietary intervention resulted in the largest reduction in maternal gestational weight gain (3.84 kg, 2.45 to 5.22 kg), with improved pregnancy outcomes compared with other interventions. The overall evidence rating was low to very low for important outcomes such as pre-eclampsia, gestational diabetes, gestational hypertension, and preterm delivery. CONCLUSIONS Dietary and lifestyle interventions in pregnancy can reduce maternal gestational weight gain and improve outcomes for both mother and baby. Among the interventions, those based on diet are the most effective and are associated with reductions in maternal gestational weight gain and improved obstetric outcomes.",
"title": "Effects of interventions in pregnancy on maternal weight and obstetric outcomes: meta-analysis of randomised evidence"
},
{
"docid": "26611834",
"text": "CONTEXT Maternal depressive symptoms during pregnancy have been reported in some, but not all, studies to be associated with an increased risk of preterm birth (PTB), low birth weight (LBW), and intrauterine growth restriction (IUGR). OBJECTIVE To estimate the risk of PTB, LBW, and IUGR associated with antenatal depression. DATA SOURCES AND STUDY SELECTION We searched for English-language and non-English-language articles via the MEDLINE, PsycINFO, CINAHL, Social Work Abstracts, Social Services Abstracts, and Dissertation Abstracts International databases (January 1980 through December 2009). We aimed to include prospective studies reporting data on antenatal depression and at least 1 adverse birth outcome: PTB (<37 weeks' gestation), LBW (<2500 g), or IUGR (<10th percentile for gestational age). Of 862 reviewed studies, 29 US-published and non-US-published studies met the selection criteria. DATA EXTRACTION Information was extracted on study characteristics, antenatal depression measurement, and other biopsychosocial risk factors and was reviewed twice to minimize error. DATA SYNTHESIS Pooled relative risks (RRs) for the effect of antenatal depression on each birth outcome were calculated using random-effects methods. In studies of PTB, LBW, and IUGR that used a categorical depression measure, pooled effect sizes were significantly larger (pooled RR [95% confidence interval] = 1.39 [1.19-1.61], 1.49 [1.25-1.77], and 1.45 [1.05-2.02], respectively) compared with studies that used a continuous depression measure (1.03 [1.00-1.06], 1.04 [0.99-1.09], and 1.02 [1.00-1.04], respectively). The estimates of risk for categorically defined antenatal depression and PTB and LBW remained significant when the trim-and-fill procedure was used to correct for publication bias. The risk of LBW associated with antenatal depression was significantly larger in developing countries (RR = 2.05; 95% confidence interval, 1.43-2.93) compared with the United States (RR = 1.10; 95% confidence interval, 1.01-1.21) or European social democracies (RR = 1.16; 95% confidence interval, 0.92-1.47). Categorically defined antenatal depression tended to be associated with an increased risk of PTB among women of lower socioeconomic status in the United States. CONCLUSIONS Women with depression during pregnancy are at increased risk for PTB and LBW, although the magnitude of the effect varies as a function of depression measurement, country location, and US socioeconomic status. An important implication of these findings is that antenatal depression should be identified through universal screening and treated.",
"title": "A meta-analysis of depression during pregnancy and the risk of preterm birth, low birth weight, and intrauterine growth restriction."
},
{
"docid": "12438901",
"text": "BACKGROUND For women with oestrogen receptor (ER)-positive early breast cancer, treatment with tamoxifen for 5 years substantially reduces the breast cancer mortality rate throughout the first 15 years after diagnosis. We aimed to assess the further effects of continuing tamoxifen to 10 years instead of stopping at 5 years. METHODS In the worldwide Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) trial, 12,894 women with early breast cancer who had completed 5 years of treatment with tamoxifen were randomly allocated to continue tamoxifen to 10 years or stop at 5 years (open control). Allocation (1:1) was by central computer, using minimisation. After entry (between 1996 and 2005), yearly follow-up forms recorded any recurrence, second cancer, hospital admission, or death. We report effects on breast cancer outcomes among the 6846 women with ER-positive disease, and side-effects among all women (with positive, negative, or unknown ER status). Long-term follow-up still continues. This study is registered, number ISRCTN19652633. FINDINGS Among women with ER-positive disease, allocation to continue tamoxifen reduced the risk of breast cancer recurrence (617 recurrences in 3428 women allocated to continue vs 711 in 3418 controls, p=0·002), reduced breast cancer mortality (331 deaths vs 397 deaths, p=0·01), and reduced overall mortality (639 deaths vs 722 deaths, p=0·01). The reductions in adverse breast cancer outcomes appeared to be less extreme before than after year 10 (recurrence rate ratio [RR] 0·90 [95% CI 0·79–1·02] during years 5–9 and 0·75 [0·62–0·90] in later years; breast cancer mortality RR 0·97 [0·79–1·18] during years 5–9 and 0·71 [0·58–0·88] in later years). The cumulative risk of recurrence during years 5–14 was 21·4% for women allocated to continue versus 25·1% for controls; breast cancer mortality during years 5–14 was 12·2% for women allocated to continue versus 15·0% for controls (absolute mortality reduction 2·8%). Treatment allocation seemed to have no effect on breast cancer outcome among 1248 women with ER-negative disease, and an intermediate effect among 4800 women with unknown ER status. Among all 12,894 women, mortality without recurrence from causes other than breast cancer was little affected (691 deaths without recurrence in 6454 women allocated to continue versus 679 deaths in 6440 controls; RR 0·99 [0·89–1·10]; p=0·84). For the incidence (hospitalisation or death) rates of specific diseases, RRs were as follows: pulmonary embolus 1·87 (95% CI 1·13–3·07, p=0·01 [including 0·2% mortality in both treatment groups]), stroke 1·06 (0·83–1·36), ischaemic heart disease 0·76 (0·60–0·95, p=0·02), and endometrial cancer 1·74 (1·30–2·34, p=0·0002). The cumulative risk of endometrial cancer during years 5–14 was 3·1% (mortality 0·4%) for women allocated to continue versus 1·6% (mortality 0·2%) for controls (absolute mortality increase 0·2%). INTERPRETATION For women with ER-positive disease, continuing tamoxifen to 10 years rather than stopping at 5 years produces a further reduction in recurrence and mortality, particularly after year 10. These results, taken together with results from previous trials of 5 years of tamoxifen treatment versus none, suggest that 10 years of tamoxifen treatment can approximately halve breast cancer mortality during the second decade after diagnosis. FUNDING Cancer Research UK, UK Medical Research Council, AstraZeneca UK, US Army, EU-Biomed.",
"title": "Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial"
},
{
"docid": "16086778",
"text": "The biological antagonism between Notch and Numb controls the proliferative/differentiative balance in development and homeostasis. Although altered Notch signaling has been linked to human diseases, including cancer, evidence for a substantial involvement of Notch in human tumors has remained elusive. Here, we show that Numb-mediated control on Notch signaling is lost in ∼50% of human mammary carcinomas, due to specific Numb ubiquitination and proteasomal degradation. Mechanistically, Numb operates as an oncosuppressor, as its ectopic expression in Numb-negative, but not in Numb-positive, tumor cells inhibits proliferation. Increased Notch signaling is observed in Numb-negative tumors, but reverts to basal levels after enforced expression of Numb. Conversely, Numb silencing increases Notch signaling in normal breast cells and in Numb-positive breast tumors. Finally, growth suppression of Numb-negative, but not Numb-positive, breast tumors can be achieved by pharmacological inhibition of Notch. Thus, the Numb/Notch biological antagonism is relevant to the homeostasis of the normal mammary parenchyma and its subversion contributes to human mammary carcinogenesis.",
"title": "Loss of negative regulation by Numb over Notch is relevant to human breast carcinogenesis"
},
{
"docid": "36432234",
"text": "Wedelolactone, a plant coumestan, was shown to act as anti-cancer agent for breast and prostate carcinomas in vitro and in vivo targeting multiple cellular proteins including androgen receptors, 5-lipoxygenase and topoisomerase IIα. It is cytotoxic to breast, prostate, pituitary and myeloma cancer cell lines in vitro at μM concentrations. In this study, however, a novel biological activity of nM dose of wedelolactone was demonstrated. Wedelolactone acts as agonist of estrogen receptors (ER) α and β as demonstrated by transactivation of estrogen response element (ERE) in cells transiently expressing either ERα or ERβ and by molecular docking of this coumestan into ligand binding pocket of both ERα and ERβ. In breast cancer cells, wedelolactone stimulates growth of estrogen receptor-positive cells, expression of estrogen-responsive genes and activates rapid non-genomic estrogen signalling. All these effects can be inhibited by pretreatment with pure ER antagonist ICI 182,780 and they are not observed in ER-negative breast cancer cells. We conclude that wedelolactone acts as phytoestrogen in breast cancer cells by stimulating ER genomic and non-genomic signalling pathways.",
"title": "Wedelolactone induces growth of breast cancer cells by stimulation of estrogen receptor signalling."
},
{
"docid": "30786800",
"text": "BACKGROUND The International Lipid-Based Nutrient Supplements Project developed a small-quantity (20 g/d) lipid-based nutrient supplement (LNS) for pregnant and lactating women. OBJECTIVE We evaluated the effects of prenatal LNS supplementation on fetal growth. DESIGN In a community-based, partially double-blind, individually randomized controlled trial, 1320 women ≤20 wk pregnant received 60 mg Fe/400 μg folic acid (IFA), or 1-2 Recommended Dietary Allowances of 18 micronutrients, including 20 mg Fe (MMN), or LNS with the same micronutrients as the MMN group, plus 4 minerals and macronutrients contributing 118 kcal (LNS) daily until delivery. Fetal growth was compared across groups by using intention-to-treat analysis. The primary outcome was birth length. RESULTS This analysis included 1057 women (IFA = 349, MMN = 354, LNS = 354). Groups did not differ significantly in mean birth length, length-for-age z score (LAZ), head circumference, or percentage low birth length but differed in mean birth weight (P = 0.044), weight-for-age z score (WAZ; P = 0.046), and BMI-for-age z score (BMIZ; P = 0.040), with a trend toward differences in low birth weight (P = 0.069). In pairwise comparisons, the LNS group had greater mean birth weight (+85 g; P = 0.040), WAZ (+0.19; P = 0.045), and BMIZ (+0.21; P = 0.035) and a lower risk of low birth weight (RR: 0.61, 95% CI: 0.39, 0.96; P = 0.032) than did the IFA group. The other group differences were not significant. The effect of intervention was modified by mother's parity, age, height, baseline hemoglobin, household food insecurity, and child sex, with parity being the most consistent modifier. Among primiparous women (IFA = 131; MMN = 110; LNS = 128), the LNS group had greater mean birth length (+0.91 cm; P = 0.001), LAZ (+0.47; P = 0.001), weight (+237 g; P < 0.001), WAZ (+0.56; P < 0.001), BMIZ (+0.52; P < 0.001), head circumference (0.50 cm; P = 0.017), and head circumference-for-age z score (+0.40; P = 0.022) than did the IFA group; similar differences were found when comparing the LNS and MMN groups among primiparous women, and no group differences were found among multiparous women. CONCLUSION Prenatal LNS supplementation can improve fetal growth among vulnerable women in Ghana, particularly primiparous women. This trial was registered at clinicaltrials.gov as NCT00970866.",
"title": "Lipid-based nutrient supplement increases the birth size of infants of primiparous women in Ghana."
}
] |
698
|
Lmna knock-in models are appropriate for testing therapeutic approaches against Hutchinson-Gilford progeria syndrome (HGPS).
|
[
{
"docid": "22544171",
"text": "Hutchinson-Gilford progeria syndrome (HGPS) is a childhood premature aging disease caused by a spontaneous point mutation in lamin A (encoded by LMNA), one of the major architectural elements of the mammalian cell nucleus. The HGPS mutation activates an aberrant cryptic splice site in LMNA pre-mRNA, leading to synthesis of a truncated lamin A protein and concomitant reduction in wild-type lamin A. Fibroblasts from individuals with HGPS have severe morphological abnormalities in nuclear envelope structure. Here we show that the cellular disease phenotype is reversible in cells from individuals with HGPS. Introduction of wild-type lamin A protein does not rescue the cellular disease symptoms. The mutant LMNA mRNA and lamin A protein can be efficiently eliminated by correction of the aberrant splicing event using a modified oligonucleotide targeted to the activated cryptic splice site. Upon splicing correction, HGPS fibroblasts assume normal nuclear morphology, the aberrant nuclear distribution and cellular levels of lamina-associated proteins are rescued, defects in heterochromatin-specific histone modifications are corrected and proper expression of several misregulated genes is reestablished. Our results establish proof of principle for the correction of the premature aging phenotype in individuals with HGPS.",
"title": "Reversal of the cellular phenotype in the premature aging disease Hutchinson-Gilford progeria syndrome"
}
] |
[
{
"docid": "15692098",
"text": "Hutchinson-Gilford progeria syndrome (HGPS) is a rare but well known entity characterized by extreme short stature, low body weight, early loss of hair, lipodystrophy, scleroderma, decreased joint mobility, osteolysis, and facial features that resemble aged persons. Cardiovascular compromise leads to early demise. Cognitive development is normal. Data on 10 of our own cases and 132 cases from literature are presented. The incidence in the last century in the Netherlands was 1:4,000,000. Sex ratio was 1.2:1. Main first symptoms were failure to thrive (55%), hair loss (40%), skin problems (28%), and lipodystrophy (20%). Mean age at diagnosis was 2.9 years. Growth in weight was more disturbed than growth in height, and growth delay started already prenatally. Mean height > 13 years was 109.0 cm, mean weight was 14.5 kg. Osteolysis was wide-spread but not expressed, except in the viscerocranium, and remained limited to membranous formed bone. Lipodystrophy is generalized, only intra-abdominal fat depositions remain present. Cardiovascular problems are extremely variable, both in age of onset and nature. Stroke and coronary dysfunctioning are most frequent. Pathologic findings in coronaries and aorta resemble sometimes the findings in elderly persons, but can also be much more limited. Loss of smooth muscle cells seems the most important finding. Mean age of demise was 12.6 years. Patients can be subdivided in patients with classical HGPS, which follows an autosomal dominant pattern of inheritance, (almost) all cases representing spontaneous mutations, and in non-classical progeria, in whom growth can be less retarded, scalp hair remains present for a longer time, lipodystrophy is more slowly progressive, osteolysis is more expressed except in the face, and survival well into adulthood is not uncommon. Pattern of inheritance of non-classical progeria is most probably autosomal recessive. The cause of HGPS is an abnormally formed Lamin A, either directly by a mutated LMNA gene, or through abnormal posttranslational processing (ZMPSTE24 gene mutations). Of 34 LMNA mutations found in progeria patients, there were 26 classical p. G608G mutations (76%). Pathogenesis is most likely to follow several different pathways. Potential therapeutic strategies are developed along these lines and include RNA interference techniques and inhibition of the dominant-negative influence of abnormally formed Lamin A on polymerization with normally formed Lamin A.",
"title": "Hutchinson-Gilford progeria syndrome: review of the phenotype"
},
{
"docid": "834336",
"text": "Hutchinson–Gilford progeria syndrome (HGPS; OMIM 176670) is an extremely rare but devastating disorder that mimics premature aging.1–3 Affected children appear normal at birth but typically develop failure to thrive in the first two years. Other features include alopecia, micrognathia, loss of subcutaneous fat with prominent veins, abnormal dentition, sclerodermatous skin changes, and osteolysis of the clavicles and distal phalanges. The mean age of death is at age 13 years, most commonly due to atherosclerosis. HGPS is mainly sporadic in occurrence, but a genetic cause has now been implicated following the identification of de novo heterozygous mutations in the LMNA gene in the majority of HGPS patients.4,5 A single family showing autosomal recessive inheritance of homozygous LMNA mutations has also been reported.6 LMNA encodes lamins A and C, components of the nuclear lamina, a meshwork underlying the nuclear envelope that serves as a structural support and is also thought to contribute to chromatin organisation and the regulation of gene expression.7,8 Interestingly, mutations in LMNA have recently been associated with at least eight inherited disorders, known as laminopathies, with differential dystrophic effects on a variety of tissues including muscle, neurones, skin, bone, and adipose tissue (reviewed in Mounkes et al 9). However, the realisation that these disorders share common genetic defects has led to clinical re-evaluation, with emerging evidence of significant phenotypic overlap.10 Hence the laminopathies might reasonably be considered as a spectrum of related diseases. HGPS has phenotypic similarities to several other laminopathies, in particular the atypical Werner’s syndrome11 and mandibuloacral dysplasia (MAD; OMIM 248370 and 608612).12 These diseases are associated with lipodystrophy,3,13 which is the most prominent feature of another laminopathy, familial partial lipodystrophy of the Dunnigan variety (OMIM 151660).14 MAD has been further classified as two …",
"title": "Compound heterozygous ZMPSTE24 mutations reduce prelamin A processing and result in a severe progeroid phenotype."
},
{
"docid": "34747208",
"text": "Mutations in the nuclear structural protein lamin A cause the premature aging syndrome Hutchinson-Gilford progeria (HGPS). Whether lamin A plays any role in normal aging is unknown. We show that the same molecular mechanism responsible for HGPS is active in healthy cells. Cell nuclei from old individuals acquire defects similar to those of HGPS patient cells, including changes in histone modifications and increased DNA damage. Age-related nuclear defects are caused by sporadic use, in healthy individuals, of the same cryptic splice site in lamin A whose constitutive activation causes HGPS. Inhibition of this splice site reverses the nuclear defects associated with aging. These observations implicate lamin A in physiological aging.",
"title": "Lamin A-dependent nuclear defects in human aging."
},
{
"docid": "14178995",
"text": "The genetic diseases Hutchinson-Gilford progeria syndrome (HGPS) and restrictive dermopathy (RD) arise from accumulation of farnesylated prelamin A because of defects in the lamin A maturation pathway. Both of these diseases exhibit symptoms that can be viewed as accelerated aging. The mechanism by which accumulation of farnesylated prelamin A leads to these accelerated aging phenotypes is not understood. Here we present evidence that in HGPS and RD fibroblasts, DNA damage checkpoints are persistently activated because of the compromise in genomic integrity. Inactivation of checkpoint kinases Ataxia-telangiectasia-mutated (ATM) and ATR (ATM- and Rad3-related) in these patient cells can partially overcome their early replication arrest. Treatment of patient cells with a protein farnesyltransferase inhibitor (FTI) did not result in reduction of DNA double-strand breaks and damage checkpoint signaling, although the treatment significantly reversed the aberrant shape of their nuclei. This suggests that DNA damage accumulation and aberrant nuclear morphology are independent phenotypes arising from prelamin A accumulation in these progeroid syndromes. Since DNA damage accumulation is an important contributor to the symptoms of HGPS, our results call into question the possibility of treatment of HGPS with FTIs alone.",
"title": "Summary"
},
{
"docid": "7468449",
"text": "Ever since the first demonstration of their repetitive sequence and unique replication pathway, telomeres have beguiled researchers with how they function in protecting chromosome ends. Of course much has been learned over the years, and we now appreciate that telomeres are comprised of the multimeric protein/DNA shelterin complex and that the formation of t-loops provides protection from DNA damage machinery. Deriving their name from D-loops, t-loops are generated by the insertion of the 3' overhang into telomeric repeats facilitated by the binding of TRF2. Recent studies have uncovered novel forms of chromosome end-structure that may implicate telomere organization in cellular processes beyond its essential role in telomere protection and homeostasis. In particular, we have recently described that t-loops form in a TRF2-dependent manner at interstitial telomere repeat sequences, which we termed interstitial telomere loops (ITLs). These structures are also dependent on association of lamin A/C, a canonical component of the nucleoskeleton that is mutated in myriad human diseases, including human segmental progeroid syndromes. Since ITLs are associated with telomere stability and require functional lamin A/C, our study suggests a mechanistic link between cellular aging (replicative senescence induced by telomere shortening) and organismal aging (modeled by Hutchinson Gilford Progeria Syndrome). Here we speculate on other potential ramifications of ITL formation, from gene expression to genome stability to chromosome structure.",
"title": "A beginning of the end: new insights into the functional organization of telomeres"
},
{
"docid": "31324978",
"text": "Progerias are rare genetic diseases characterized by premature aging. Several progeroid disorders are caused by mutations that lead to the accumulation of a lipid-modified (farnesylated) form of prelamin A, a protein that contributes to the structural scaffolding for the cell nucleus. In progeria, the accumulation of farnesyl-prelamin A disrupts this scaffolding, leading to misshapen nuclei. Previous studies have shown that farnesyltransferase inhibitors (FTIs) reverse this cellular abnormality. We tested the efficacy of an FTI (ABT-100) in Zmpste24-deficient mice, a mouse model of progeria. The FTI-treated mice exhibited improved body weight, grip strength, bone integrity, and percent survival at 20 weeks of age. These results suggest that FTIs may have beneficial effects in humans with progeria.",
"title": "A protein farnesyltransferase inhibitor ameliorates disease in a mouse model of progeria."
},
{
"docid": "7239105",
"text": "Remarkable advances have been made in recent years towards therapeutics for cognitive impairment in individuals with Down syndrome (DS) by using mouse models. In this review, we briefly describe the phenotypes of mouse models that represent outcome targets for drug testing, the behavioral tests used to assess impairments in cognition and the known mechanisms of action of several drugs that are being used in preclinical studies or are likely to be tested in clinical trials. Overlaps in the distribution of targets and in the pathways that are affected by these diverse drugs in the trisomic brain suggest new avenues for DS research and drug development.",
"title": "The use of mouse models to understand and improve cognitive deficits in Down syndrome"
},
{
"docid": "38355793",
"text": "OBJECTIVE A20 is a TNF-inducible primary response gene, which has been found to have antiapoptotic function in several cancer cells. This study investigates A20 expression in human glioma tissues and four glioma cell lines, and its effect on tumorigenesis of glioma cells and a mouse tumor model. METHODS Human glioma tissue samples and cells were subject to reverse transcription-PCR (RT-PCR), western blotting and immunohistochemistry. Glioma cells was tested by flow cytometry. A xenograft tumor model in mice was utilized to examine the knock-down effect of specific A20 siRNAs on tumorigenesis. RESULTS A20 was overexpressed in clinical glioma tissue samples (63.9%) and correlated with clinical staging. All four human glioma cell lines expressed A20, among which U87 displayed the strongest expression signals. Inhibiting A20 expression by siRNAs in vitro reduced the growth rates of glioma cells and resulted in G1/S arrest and increased apoptosis. In a mouse tumor model, local administration of siRNA significantly suppressed solid tumor growth. CONCLUSIONS A20 was overexpressed both in human glioma tissues and cell lines, and inhibiting A20 expression greatly slowed tumor cell growth in culture and in mice. These findings indicated that A20 is involved in tumorigenesis of human glioma, and may serve as a future therapeutic target.",
"title": "A20 is overexpressed in glioma cells and may serve as a potential therapeutic target."
},
{
"docid": "31844040",
"text": "Two-component systems (TCSs) are widely employed by bacteria to sense specific external signals and conduct an appropriate response via a phosphorylation cascade within the cell. The TCS of the agr operon in the bacterium Staphylococcus aureus forms part of a regulatory process termed quorum sensing, a cell-to-cell communication mechanism used to assess population density. Since S. aureus manipulates this \"knowledge\" in order to co-ordinate production of its armoury of exotoxin virulence factors required to promote infection, it is important to understand fully how this process works. We present three models of the agr operon, each incorporating a different phosphorylation cascade for the TCS since the precise nature of the cascade is not fully understood. Using numerical and asymptotic techniques we examine the effects of inhibitor therapy, a novel approach to controlling bacterial infection through the attenuation of virulence, on each of these three cascades. We present results which, if evaluated against appropriate experimental data, provide insights into the potential effectiveness of such therapy. Moreover, the TCS models presented here are of broad relevance given that TCSs are widely conserved throughout the bacterial kingdom.",
"title": "A mathematical investigation of the effects of inhibitor therapy on three putative phosphorylation cascades governing the two-component system of the agr operon."
},
{
"docid": "18414462",
"text": "Although the lung is a defining feature of air-breathing animals, the pathway controlling the formation of type I pneumocytes, the cells that mediate gas exchange, is poorly understood. In contrast, the glucocorticoid receptor and its cognate ligand have long been known to promote type II pneumocyte maturation; prenatal administration of glucocorticoids is commonly used to attenuate the severity of infant respiratory distress syndrome (RDS). Here we show that knock-in mutations of the nuclear co-repressor SMRT (silencing mediator of retinoid and thyroid hormone receptors) in C57BL/6 mice (SMRTmRID) produces a previously unidentified respiratory distress syndrome caused by prematurity of the type I pneumocyte. Though unresponsive to glucocorticoids, treatment with anti-thyroid hormone drugs (propylthiouracil or methimazole) completely rescues SMRT-induced RDS, suggesting an unrecognized and essential role for the thyroid hormone receptor (TR) in lung development. We show that TR and SMRT control type I pneumocyte differentiation through Klf2, which, in turn, seems to directly activate the type I pneumocyte gene program. Conversely, mice without lung Klf2 lack mature type I pneumocytes and die shortly after birth, closely recapitulating the SMRTmRID phenotype. These results identify TR as a second nuclear receptor involved in lung development, specifically type I pneumocyte differentiation, and suggest a possible new type of therapeutic option in the treatment of RDS that is unresponsive to glucocorticoids.",
"title": "Thyroid Hormone Receptor Repression Linked to Type I Pneumocyte Associated Respiratory Distress Syndrome"
},
{
"docid": "16232581",
"text": "We develop a reversible jump Markov chain Monte Carlo approach to estimating the posterior distribution of phylogenies based on aligned DNA/RNA sequences under several hierarchical evolutionary models. Using a proper, yet nontruncated and uninformative prior, we demonstrate the advantages of the Bayesian approach to hypothesis testing and estimation in phylogenetics by comparing different models for the infinitesimal rates of change among nucleotides, for the number of rate classes, and for the relationships among branch lengths. We compare the relative probabilities of these models and the appropriateness of a molecular clock using Bayes factors. Our most general model, first proposed by Tamura and Nei, parameterizes the infinitesimal change probabilities among nucleotides (A, G, C, T/U) into six parameters, consisting of three parameters for the nucleotide stationary distribution, two rate parameters for nucleotide transitions, and another parameter for nucleotide transversions. Nested models include the Hasegawa, Kishino, and Yano model with equal transition rates and the Kimura model with a uniform stationary distribution and equal transition rates. To illustrate our methods, we examine simulated data, 16S rRNA sequences from 15 contemporary eubacteria, halobacteria, eocytes, and eukaryotes, 9 primates, and the entire HIV genome of 11 isolates. We find that the Kimura model is too restrictive, that the Hasegawa, Kishino, and Yano model can be rejected for some data sets, that there is evidence for more than one rate class and a molecular clock among similar taxa, and that a molecular clock can be rejected for more distantly related taxa.",
"title": "Bayesian selection of continuous-time Markov chain evolutionary models."
},
{
"docid": "2264455",
"text": "There is no licenced vaccine against any human parasitic disease and Plasmodium falciparum malaria, a major cause of infectious mortality, presents a great challenge to vaccine developers. This has led to the assessment of a wide variety of approaches to malaria vaccine design and development, assisted by the availability of a safe challenge model for small-scale efficacy testing of vaccine candidates. Malaria vaccine development has been at the forefront of assessing many new vaccine technologies including novel adjuvants, vectored prime-boost regimes and the concept of community vaccination to block malaria transmission. Most current vaccine candidates target a single stage of the parasite's life cycle and vaccines against the early pre-erythrocytic stages have shown most success. A protein in adjuvant vaccine, working through antibodies against sporozoites, and viral vector vaccines targeting the intracellular liver-stage parasite with cellular immunity show partial efficacy in humans, and the anti-sporozoite vaccine is currently in phase III trials. However, a more effective malaria vaccine suitable for widespread cost-effective deployment is likely to require a multi-component vaccine targeting more than one life cycle stage. The most attractive near-term approach to develop such a product is to combine existing partially effective pre-erythrocytic vaccine candidates.",
"title": "Vaccines against malaria"
},
{
"docid": "33884866",
"text": "OBJECTIVE The sphingosine-1-phosphate (S1P) receptor agonist fingolimod (FTY720), that has shown efficacy in advanced multiple sclerosis clinical trials, decreases reperfusion injury in heart, liver, and kidney. We therefore tested the therapeutic effects of fingolimod in several rodent models of focal cerebral ischemia. To assess the translational significance of these findings, we asked whether fingolimod improved long-term behavioral outcomes, whether delayed treatment was still effective, and whether neuroprotection can be obtained in a second species. METHODS We used rodent models of middle cerebral artery occlusion and cell-culture models of neurotoxicity and inflammation to examine the therapeutic potential and mechanisms of neuroprotection by fingolimod. RESULTS In a transient mouse model, fingolimod reduced infarct size, neurological deficit, edema, and the number of dying cells in the core and periinfarct area. Neuroprotection was accompanied by decreased inflammation, as fingolimod-treated mice had fewer activated neutrophils, microglia/macrophages, and intercellular adhesion molecule-1 (ICAM-1)-positive blood vessels. Fingolimod-treated mice showed a smaller infarct and performed better in behavioral tests up to 15 days after ischemia. Reduced infarct was observed in a permanent model even when mice were treated 4 hours after ischemic onset. Fingolimod also decreased infarct size in a rat model of focal ischemia. Fingolimod did not protect primary neurons against glutamate excitotoxicity or hydrogen peroxide, but decreased ICAM-1 expression in brain endothelial cells stimulated by tumor necrosis factor alpha. INTERPRETATION These findings suggest that anti-inflammatory mechanisms, and possibly vasculoprotection, rather than direct effects on neurons, underlie the beneficial effects of fingolimod after stroke. S1P receptors are a highly promising target in stroke treatment.",
"title": "Fingolimod provides long-term protection in rodent models of cerebral ischemia."
},
{
"docid": "34873974",
"text": "OBJECTIVE To obtain summary estimates of the accuracy of a single baseline measurement of the Elecsys Troponin T high-sensitive assay (Roche Diagnostics) for the diagnosis of acute myocardial infarction in patients presenting to the emergency department. DESIGN Systematic review and meta-analysis of diagnostic test accuracy studies. DATA SOURCES Medline, Embase, and other relevant electronic databases were searched for papers published between January 2006 and December 2013. STUDY SELECTION Studies were included if they evaluated the diagnostic accuracy of a single baseline measurement of Elecsys Troponin T high-sensitive assay for the diagnosis of acute myocardial infarction in patients presenting to the emergency department with suspected acute coronary syndrome. STUDY APPRAISAL AND DATA SYNTHESIS The first author screened all titles and abstracts identified through the searches and selected all potentially relevant papers. The screening of the full texts, the data extraction, and the methodological quality assessment, using the adapted QUADAS-2 tool, were conducted independently by two reviewers with disagreements being resolved through discussion or arbitration. If appropriate, meta-analysis was conducted using the hierarchical bivariate model. RESULTS Twenty three studies reported the performance of the evaluated assay at presentation. The results for 14 ng/L and 3-5 ng/L cut-off values were pooled separately. At 14 ng/L (20 papers), the summary sensitivity was 89.5% (95% confidence interval 86.3% to 92.1%) and the summary specificity was 77.1% (68.7% to 83.7%). At 3-5 ng/L (six papers), the summary sensitivity was 97.4% (94.9% to 98.7%) and the summary specificity was 42.4% (31.2% to 54.5%). This means that if 21 of 100 consecutive patients have the target condition (21%, the median prevalence across the studies), 2 (95% confidence interval 2 to 3) of 21 patients with acute myocardial infarction will be missed (false negatives) if 14 ng/L is used as a cut-off value and 18 (13 to 25) of 79 patients without acute myocardial infarction will test positive (false positives). If the 3-5 ng/L cut-off value is used, <1 (0 to 1) patient with acute myocardial infarction will be missed and 46 (36 to 54) patients without acute myocardial infarction will test positive. CONCLUSIONS The results indicate that a single baseline measurement of the Elecsys Troponin T high-sensitive assay could be used to rule out acute myocardial infarction if lower cut-off values such as 3 ng/L or 5 ng/L are used. However, this method should be part of a comprehensive triage strategy and may not be appropriate for patients who present less than three hours after symptom onset. Care must also be exercised because of the higher imprecision of the evaluated assay and the greater effect of lot-to-lot reagent variation at low troponin concentrations. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration number CRD42013003926.",
"title": "Diagnostic accuracy of single baseline measurement of Elecsys Troponin T high-sensitive assay for diagnosis of acute myocardial infarction in emergency department: systematic review and meta-analysis"
},
{
"docid": "24496245",
"text": "Genetic evidence implicates the loss of bone morphogenetic protein type II receptor (BMPR-II) signaling in the endothelium as an initiating factor in pulmonary arterial hypertension (PAH). However, selective targeting of this signaling pathway using BMP ligands has not yet been explored as a therapeutic strategy. Here, we identify BMP9 as the preferred ligand for preventing apoptosis and enhancing monolayer integrity in both pulmonary arterial endothelial cells and blood outgrowth endothelial cells from subjects with PAH who bear mutations in the gene encoding BMPR-II, BMPR2. Mice bearing a heterozygous knock-in allele of a human BMPR2 mutation, R899X, which we generated as an animal model of PAH caused by BMPR-II deficiency, spontaneously developed PAH. Administration of BMP9 reversed established PAH in these mice, as well as in two other experimental PAH models, in which PAH develops in response to either monocrotaline or VEGF receptor inhibition combined with chronic hypoxia. These results demonstrate the promise of direct enhancement of endothelial BMP signaling as a new therapeutic strategy for PAH.",
"title": "Selective enhancement of endothelial BMPR-II with BMP9 reverses pulmonary arterial hypertension"
},
{
"docid": "7317051",
"text": "Pancreatic ductal adenocarcinoma (PDA) represents an unmet therapeutic challenge. PDA is addicted to the activity of the mutated KRAS oncogene which is considered so far an undruggable therapeutic target. We propose an approach to target KRAS effectively in patients using RNA interference. To meet this challenge, we have developed a local prolonged siRNA delivery system (Local Drug EluteR, LODER) shedding siRNA against the mutated KRAS (siG12D LODER). The siG12D LODER was assessed for its structural, release, and delivery properties in vitro and in vivo. The effect of the siG12D LODER on tumor growth was assessed in s.c. and orthotopic mouse models. KRAS silencing effect was further assessed on the KRAS downstream signaling pathway. The LODER-encapsulated siRNA was stable and active in vivo for 155 d. Treatment of PDA cells with siG12D LODER resulted in a significant decrease in KRAS levels, leading to inhibition of proliferation and epithelial-mesenchymal transition. In vivo, siG12D LODER impeded the growth of human pancreatic tumor cells and prolonged mouse survival. We report a reproducible and safe delivery platform based on a miniature biodegradable polymeric matrix, for the controlled and prolonged delivery of siRNA. This technology provides the following advantages: (i) siRNA is protected from degradation; (ii) the siRNA is slowly released locally within the tumor for prolonged periods; and (iii) the siG12D LODER elicits a therapeutic effect, thereby demonstrating that mutated KRAS is indeed a druggable target.",
"title": "Mutant KRAS is a druggable target for pancreatic cancer."
},
{
"docid": "14116046",
"text": "Retinoic acid-related orphan receptors RORα and RORγ play a regulatory role in lipid/glucose homeostasis and various immune functions, and have been implicated in metabolic syndrome and several inflammatory diseases. RORα-deficient mice are protected against age- and diet-induced obesity, hepatosteatosis, and insulin resistance. The resistance to hepatosteatosis in RORα-deficient mice is related to the reduced expression of several genes regulating lipid synthesis, transport, and storage. Adipose tissue-associated inflammation, which plays a critical role in the development of insulin resistance, is considerably diminished in RORα-deficient mice as indicated by the reduced infiltration of M1 macrophages and decreased expression of many proinflammatory genes. Deficiency in RORγ also protects against diet-induced insulin resistance by a mechanism that appears different from that in RORα deficiency. Recent studies indicated that RORs provide an important link between the circadian clock machinery and its regulation of metabolic genes and metabolic syndrome. As ligand-dependent transcription factors, RORs may provide novel therapeutic targets in the management of obesity and associated metabolic diseases, including hepatosteatosis, adipose tissue-associated inflammation, and insulin resistance.",
"title": "Retinoic acid-related orphan receptors α and γ: key regulators of lipid/glucose metabolism, inflammation, and insulin sensitivity"
},
{
"docid": "2837758",
"text": "Epitope vaccine is a promising option for therapeutic vaccination against Helicobacter pylori (H. pylori) infection. In this study, we constructed a multi-epitope vaccine with five epitopes and mucosal adjuvant E. coli heat-labile enterotoxin B subunit (LTB) named HUepi-LTB and evaluated its therapeutic effect against H. pylori infection in BALB/c mice model. HUepi-LTB containing three Th epitopes from UreB and two B cell epitopes from UreB and HpaA was constructed and expressed in E. coli. Oral therapeutic immunization with HUepi-LTB significantly decreased H. pylori colonization compared with oral immunization with PBS, and the protection was correlated with antigen-specific CD4+ T cells and IgG and mucosal IgA antibody responses. This multi-epitope vaccine may be a promising vaccine candidate that may help to control H. pylori infection.",
"title": "Therapeutic efficacy of a multi-epitope vaccine against Helicobacter pylori infection in BALB/c mice model."
},
{
"docid": "8690595",
"text": "Although genetic association studies have been with us for many years, even for the simplest analyses there is little consensus on the most appropriate statistical procedures. Here I give an overview of statistical approaches to population association studies, including preliminary analyses (Hardy–Weinberg equilibrium testing, inference of phase and missing data, and SNP tagging), and single-SNP and multipoint tests for association. My goal is to outline the key methods with a brief discussion of problems (population structure and multiple testing), avenues for solutions and some ongoing developments.",
"title": "A tutorial on statistical methods for population association studies"
},
{
"docid": "878526",
"text": "Despite progress in the development of drugs that efficiently target cancer cells, treatments for metastatic tumours are often ineffective. The now well-established dependency of cancer cells on their microenvironment suggests that targeting the non-cancer-cell component of the tumour might form a basis for the development of novel therapeutic approaches. However, the as-yet poorly characterized contribution of host responses during tumour growth and metastatic progression represents a limitation to exploiting this approach. Here we identify neutrophils as the main component and driver of metastatic establishment within the (pre-)metastatic lung microenvironment in mouse breast cancer models. Neutrophils have a fundamental role in inflammatory responses and their contribution to tumorigenesis is still controversial. Using various strategies to block neutrophil recruitment to the pre-metastatic site, we demonstrate that neutrophils specifically support metastatic initiation. Importantly, we find that neutrophil-derived leukotrienes aid the colonization of distant tissues by selectively expanding the sub-pool of cancer cells that retain high tumorigenic potential. Genetic or pharmacological inhibition of the leukotriene-generating enzyme arachidonate 5-lipoxygenase (Alox5) abrogates neutrophil pro-metastatic activity and consequently reduces metastasis. Our results reveal the efficacy of using targeted therapy against a specific tumour microenvironment component and indicate that neutrophil Alox5 inhibition may limit metastatic progression.",
"title": "Neutrophils support lung colonization of metastasis-initiating breast cancer cells"
},
{
"docid": "20372201",
"text": "A growing body of evidence supports the notion that malignant tumors are heterogeneous and contain diverse subpopulations of cells with unique characteristics including the ability to initiate a tumor and metastasize. This phenomenon might be explained by the so-called cancer stem cell (CSC) theory. Recent technological developments have allowed a deeper understanding and characterization of CSCs. Even though the application of this theory to hematopoietic malignancies and solid tumors holds promise for new ways to treat cancer, it also brings some skepticism. Efficacious therapeutic approaches targeting the CSC population should be explored to overcome therapeutic failure and improve patient outcomes. This review will focus on the intrinsic and extrinsic regulation of CSCs, as well as the development of therapeutic approaches against CSCs, predominantly focusing on gastrointestinal malignancies.",
"title": "Cancer stem cell theory in gastrointestinal malignancies: recent progress and upcoming challenges"
},
{
"docid": "4544916",
"text": "To efficiently counteract pathogens, plants rely on a complex set of immune responses that are tightly regulated to allow the timely activation, appropriate duration and adequate amplitude of defense programs. The coordination of the plant immune response is known to require the activity of the ubiquitin/proteasome system, which controls the stability of proteins in eukaryotes. Here, we demonstrate that the N-end rule pathway, a subset of the ubiquitin/proteasome system, regulates the defense against a wide range of bacterial and fungal pathogens in the model plant Arabidopsis thaliana. We show that this pathway positively regulates the biosynthesis of plant-defense metabolites such as glucosinolates, as well as the biosynthesis and response to the phytohormone jasmonic acid, which plays a key role in plant immunity. Our results also suggest that the arginylation branch of the N-end rule pathway regulates the timing and amplitude of the defense program against the model pathogen Pseudomonas syringae AvrRpm1.",
"title": "The N-end rule pathway regulates pathogen responses in plants."
},
{
"docid": "17682477",
"text": "To test the feasibility of a single T-cell manipulation to eliminate alloreactivity while sparing antiviral and antitumor T cells, we infused 12 haploidentical hematopoietic stem cell transplant patients with increasing numbers of alloreplete haploidentical T cells expressing the inducible caspase 9 suicide gene (iC9-T cells). We determined whether the iC9-T cells produced immune reconstitution and if any resultant graft-versus-host disease (GVHD) could be controlled by administration of a chemical inducer of dimerization (CID; AP1903/Rimiducid). All patients receiving >10(4) alloreplete iC9-T lymphocytes per kilogram achieved rapid reconstitution of immune responses toward 5 major pathogenic viruses and concomitant control of active infections. Four patients received a single AP1903 dose. CID infusion eliminated 85% to 95% of circulating CD3(+)CD19(+) T cells within 30 minutes, with no recurrence of GVHD within 90 days. In one patient, symptoms and signs of GVHD-associated cytokine release syndrome (CRS-hyperpyrexia, high levels of proinflammatory cytokines, and rash) resolved within 2 hours of AP1903 infusion. One patient with varicella zoster virus meningitis and acute GVHD had iC9-T cells present in the cerebrospinal fluid, which were reduced by >90% after CID. Notably, virus-specific T cells recovered even after AP1903 administration and continued to protect against infection. Hence, alloreplete iC9-T cells can reconstitute immunity posttransplant and administration of CID can eliminate them from both peripheral blood and the central nervous system (CNS), leading to rapid resolution of GVHD and CRS. The approach may therefore be useful for the rapid and effective treatment of toxicities associated with infusion of engineered T lymphocytes. This trial was registered at www.clinicaltrials.gov as #NCT01494103.",
"title": "Inducible caspase-9 suicide gene controls adverse effects from alloreplete T cells after haploidentical stem cell transplantation."
},
{
"docid": "44827480",
"text": "BACKGROUND Few data exist about the implementation of contemporary oral antiplatelet treatment guidelines in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). METHODS GReek AntiPlatelet rEgistry (GRAPE), initiated on January 2012, is a prospective, observational, multicenter cohort study focusing on contemporary use of P2Y12 inhibitors. In 1434 patients we evaluated appropriateness of P2Y12 selection initially and at discharge by applying an eligibility-assessing algorithm based on P2Y12 inhibitors' contraindications/specific warnings and precautions. RESULTS Appropriate, less preferable and inappropriate P2Y12 inhibitor selections were made initially in 45.8%, 47.2% and 6.6% and at discharge in 64.1%, 29.2% and 6.6% of patients, respectively. The selection of clopidogrel was most commonly less preferable, both initially (69.7%) and at discharge (75.6%). Appropriate selection of newer agents was high initially (79.2%-82.8%), with further increase as selection at discharge (89.4%-89.8%). Inappropriate selection of the newer agents was 17.2%-20.8% initially, decreasing to 10.2%-10.6% at discharge. Conditions and co-medications related to increased bleeding risk, presentation with ST elevation myocardial infarction and the absence of reperfusion within the first 24h were the most powerful predictors of appropriate P2Y12 selection initially, whereas age ≥75 years, conditions and co-medications related to increased bleeding risk and regional trends mostly affected appropriate P2Y12 selection at discharge. CONCLUSIONS In GRAPE, adherence with the recently released guidelines on oral antiplatelet therapy was satisfactory. Clopidogrel was most commonly used as a less preferable selection, while prasugrel or ticagrelor selection was mostly appropriate. Certain factors may predict initial and at discharge guideline implementation. Clinical Trial Registration-clinicaltrials.gov Identifier: NCT01774955 http://clinicaltrials.gov/.",
"title": "Implementation of contemporary oral antiplatelet treatment guidelines in patients with acute coronary syndrome undergoing percutaneous coronary intervention: a report from the GReek AntiPlatelet rEgistry (GRAPE)."
},
{
"docid": "8133050",
"text": "Many microparasites infect new hosts with specialized life stages, requiring a subset of the parasite population to forgo proliferation and develop into transmission forms. Transmission stage production influences infectivity, host exploitation, and the impact of medical interventions like drug treatment. Predicting how parasites will respond to public health efforts on both epidemiological and evolutionary timescales requires understanding transmission strategies. These strategies can rarely be observed directly and must typically be inferred from infection dynamics. Using malaria as a case study, we test previously described methods for inferring transmission stage investment against simulated data generated with a model of within-host infection dynamics, where the true transmission investment is known. We show that existing methods are inadequate and potentially very misleading. The key difficulty lies in separating transmission stages produced by different generations of parasites. We develop a new approach that performs much better on simulated data. Applying this approach to real data from mice infected with a single Plasmodium chabaudi strain, we estimate that transmission investment varies from zero to 20%, with evidence for variable investment over time in some hosts, but not others. These patterns suggest that, even in experimental infections where host genetics and other environmental factors are controlled, parasites may exhibit remarkably different patterns of transmission investment.",
"title": "Quantifying Transmission Investment in Malaria Parasites"
},
{
"docid": "12030735",
"text": "OBJECTIVE Limited information is available about the metabolic syndrome in Asians. Furthermore, the definition of central obesity using waist circumference may not be appropriate for Asians. The objectives of this study were to determine the optimal waist circumference for diagnosing central obesity in Asians and to estimate the prevalence of the metabolic syndrome in an Asian population. RESEARCH DESIGN AND METHODS We used data from the 1998 Singapore National Health Survey, a cross-sectional survey involving 4,723 men and women of Chinese, Malay, and Asian-Indian ethnicity aged 18-69 years. Receiver operating characteristic analysis suggested that waist circumference >80 cm in women and >90 cm in men was a more appropriate definition of central obesity in this population. The prevalence of the metabolic syndrome was then determined using the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria with and without the modified waist circumference criteria. RESULTS In Asians, decreasing waist circumference increased the crude prevalence of the metabolic syndrome from 12.2 to 17.9%. Using the modified Asian criteria, the prevalence of the metabolic syndrome increased from 2.9% in those aged 18-30 years to 31.0% in those aged 60-69 years. It was more common in men (prevalence 20.9% in men versus 15.5% in women; P < 0.001) and Asian Indians (prevalence 28.8% in Asian-Indians, 24.2% in Malays, and 14.8% in Chinese; P < 0.001). CONCLUSIONS NCEP ATP III criteria, applied to an Asian population, will underestimate the population at risk. With a lower waist circumference cutoff, the prevalence of the metabolic syndrome is comparable to that in Western populations. Ethnic differences are likely to exist between populations across Asia.",
"title": "Can we apply the National Cholesterol Education Program Adult Treatment Panel definition of the metabolic syndrome to Asians?"
},
{
"docid": "28017005",
"text": "Assessment for selection in medicine and the health professions should follow the same quality assurance processes as in-course assessment. The literature on selection is limited and is not strongly theoretical or conceptual. For written testing, there is evidence of the predictive validity of Medical College Admission Test (MCAT) for medical school and licensing examination performance. There is also evidence for the predictive validity of grade point average, particularly in combination with MCAT for graduate entry but little evidence about the predictive validity of school leaver scores. Interviews have not been shown to be robust selection measures. Studies of multiple mini-interviews have indicated good predictive validity and reliability. Of other measures used in selection, only the growing interest in personality testing appears to warrant future work. Widening access to medical and health professional programmes is an increasing priority and relates to the social accountability mandate of medical and health professional schools. While traditional selection measures do discriminate against various population groups, there is little evidence on the effect of non-traditional measures in widening access. Preparation and outreach programmes show most promise. In summary, the areas of consensus for assessment for selection are small in number. Recommendations for future action focus on the adoption of principles of good assessment and curriculum alignment, use of multi-method programmatic approaches, development of interdisciplinary frameworks and utilisation of sophisticated measurement models. The social accountability mandate of medical and health professional schools demands that social inclusion, workforce issues and widening of access are embedded in the principles of good assessment for selection.",
"title": "Assessment for selection for the health care professions and specialty training: consensus statement and recommendations from the Ottawa 2010 Conference."
},
{
"docid": "13965483",
"text": "Epitope vaccine based on the enzyme urease of Helicobacter pylori is a promising option for prophylactic and therapeutic vaccination against H. pylori infection. In our previous study, the epitope vaccine CTB-UA, which was composed of the mucosal adjuvant cholera toxin B subunit (CTB) and an epitope (UreA183–203) from the H. pylori urease A subunit (UreA) was constructed. This particular vaccine was shown to have good immunogenicity and immunoreactivity and could induce specific neutralizing antibodies, which exhibited effectively inhibitory effects on the enzymatic activity of H. pylori urease. In this study, the prophylactic and therapeutic efficacy of the epitope vaccine CTB-UA was evaluated in a BALB/c mice model. The experimental results indicated that oral prophylactic or therapeutic immunization with CTB-UA significantly decreased H. pylori colonization compared with oral immunization with PBS. The results also revealed that the protection was correlated with antigen-specific IgG, IgA, and mucosal secretory IgA antibody responses. CTB-UA may be a promising vaccine candidate for the control of H. pylori infection.",
"title": "Prophylactic and therapeutic efficacy of the epitope vaccine CTB-UA against Helicobacter pylori infection in a BALB/c mice model"
},
{
"docid": "1967410",
"text": "Although significant progress has occurred in the past 20 years regarding our understanding of Alzheimer disease pathogenesis, we have yet to identify disease-modifying therapeutics capable of substantially altering the clinical course of this prevalent neurodegenerative disease. In this short review, we discuss 2 approaches that are currently being tested clinically (γ-secretase inhibition and γ-secretase modulation) and emphasize the significant differences between these 2 therapeutic approaches. We also discuss certain genetic- and biomarker-based translational and clinical trial paradigms that may assist in developing a useful therapeutic agent.",
"title": "Potential use of γ-secretase modulators in the treatment of Alzheimer disease."
},
{
"docid": "16605494",
"text": "BACKGROUND Whereas many causes and mechanisms of neurodegenerative diseases have been identified, very few therapeutic strategies have emerged in parallel. One possible explanation is that successful treatment strategy may require simultaneous targeting of more than one molecule of pathway. A new therapeutic approach to have emerged recently is the engagement of microRNAs (miRNAs), which affords the opportunity to target multiple cellular pathways simultaneously using a single sequence. METHODOLOGY/PRINCIPAL FINDINGS We identified miR-22 as a potentially neuroprotective miRNA based on its predicted regulation of several targets implicated in Huntington's disease (histone deacetylase 4 (HDAC4), REST corepresor 1 (Rcor1) and regulator of G-protein signaling 2 (Rgs2)) and its diminished expression in Huntington's and Alzheimer's disease brains. We then tested the hypothesis that increasing cellular levels of miRNA-22 would achieve neuroprotection in in vitro models of neurodegeneration. As predicted, overexpression of miR-22 inhibited neurodegeneration in primary striatal and cortical cultures exposed to a mutated human huntingtin fragment (Htt171-82Q). Overexpression of miR-22 also decreased neurodegeneration in primary neuronal cultures exposed to 3-nitropropionic acid (3-NP), a mitochondrial complex II/III inhibitor. In addition, miR-22 improved neuronal viability in an in vitro model of brain aging. The mechanisms underlying the effects of miR-22 included a reduction in caspase activation, consistent with miR-22's targeting the pro-apoptotic activities of mitogen-activated protein kinase 14/p38 (MAPK14/p38) and tumor protein p53-inducible nuclear protein 1 (Tp53inp1). Moreover, HD-specific effects comprised not only targeting HDAC4, Rcor1 and Rgs2 mRNAs, but also decreasing focal accumulation of mutant Htt-positive foci, which occurred via an unknown mechanism. CONCLUSIONS These data show that miR-22 has multipartite anti-neurodegenerative activities including the inhibition of apoptosis and the targeting of mRNAs implicated in the etiology of HD. These results motivate additional studies to evaluate the feasibility and therapeutic efficacy of manipulating miR-22 in vivo.",
"title": "MicroRNA-22 (miR-22) Overexpression Is Neuroprotective via General Anti-Apoptotic Effects and May also Target Specific Huntington’s Disease-Related Mechanisms"
}
] |
564
|
In British Men, haplogroup I increases risk of cardiovascular disease by 50%.
|
[
{
"docid": "2867345",
"text": "BACKGROUND A sexual dimorphism exists in the incidence and prevalence of coronary artery disease--men are more commonly affected than are age-matched women. We explored the role of the Y chromosome in coronary artery disease in the context of this sexual inequity. METHODS We genotyped 11 markers of the male-specific region of the Y chromosome in 3233 biologically unrelated British men from three cohorts: the British Heart Foundation Family Heart Study (BHF-FHS), West of Scotland Coronary Prevention Study (WOSCOPS), and Cardiogenics Study. On the basis of this information, each Y chromosome was tracked back into one of 13 ancient lineages defined as haplogroups. We then examined associations between common Y chromosome haplogroups and the risk of coronary artery disease in cross-sectional BHF-FHS and prospective WOSCOPS. Finally, we undertook functional analysis of Y chromosome effects on monocyte and macrophage transcriptome in British men from the Cardiogenics Study. FINDINGS Of nine haplogroups identified, two (R1b1b2 and I) accounted for roughly 90% of the Y chromosome variants among British men. Carriers of haplogroup I had about a 50% higher age-adjusted risk of coronary artery disease than did men with other Y chromosome lineages in BHF-FHS (odds ratio 1·75, 95% CI 1·20-2·54, p=0·004), WOSCOPS (1·45, 1·08-1·95, p=0·012), and joint analysis of both populations (1·56, 1·24-1·97, p=0·0002). The association between haplogroup I and increased risk of coronary artery disease was independent of traditional cardiovascular and socioeconomic risk factors. Analysis of macrophage transcriptome in the Cardiogenics Study revealed that 19 molecular pathways showing strong differential expression between men with haplogroup I and other lineages of the Y chromosome were interconnected by common genes related to inflammation and immunity, and that some of them have a strong relevance to atherosclerosis. INTERPRETATION The human Y chromosome is associated with risk of coronary artery disease in men of European ancestry, possibly through interactions of immunity and inflammation. FUNDING British Heart Foundation; UK National Institute for Health Research; LEW Carty Charitable Fund; National Health and Medical Research Council of Australia; European Union 6th Framework Programme; Wellcome Trust.",
"title": "Inheritance of coronary artery disease in men: an analysis of the role of the Y chromosome"
}
] |
[
{
"docid": "29253460",
"text": "OBJECTIVE To assess whether sex differences exist in the angiographic severity, management and outcomes of acute coronary syndromes (ACS). METHODS The study comprised 7638 women and 19 117 men with ACS who underwent coronary angiography and were included in GRACE (Global Registry of Acute Coronary Events) from 1999-2006. Normal vessels/mild disease was defined as <50% stenosis in all epicardial vessels; advanced disease was defined as >or=one vessel with >or=50% stenosis. RESULTS Women were older than men and had higher rates of cardiovascular risk factors. Men and women presented equally with chest pain; however, jaw pain and nausea were more frequent among women. Women were more likely to have normal/mild disease (12% vs 6%, p<0.001) and less likely to have left-main and three-vessel disease (27% vs 32%, p<0.001) or undergo percutaneous coronary intervention (65% vs 68%, p<0.001). Women and men with normal and mild disease were treated less aggressively than those with advanced disease. Women with advanced disease had a higher risk of death (4% vs 3%, p<0.01). After adjustment for age and extent of disease, women were more likely to have adverse outcomes (death, myocardial infarction, stroke and rehospitalisation) at six months compared to men (odds ratio 1.24, 95% confidence interval 1.14 to 1.34); however, sex differences in mortality were no longer statistically significant. CONCLUSIONS Women with ACS were more likely to have cardiovascular disease risk factors and atypical symptoms such as nausea compared with men, but were more likely to have normal/mild angiographic coronary artery disease. Further study regarding sex differences related to disease severity is warranted.",
"title": "Sex-related differences in the presentation, treatment and outcomes among patients with acute coronary syndromes: the Global Registry of Acute Coronary Events."
},
{
"docid": "5698494",
"text": "OBJECTIVES To investigate whether statins reduce all cause mortality and major coronary and cerebrovascular events in people without established cardiovascular disease but with cardiovascular risk factors, and whether these effects are similar in men and women, in young and older (>65 years) people, and in people with diabetes mellitus. DESIGN Meta-analysis of randomised trials. DATA SOURCES Cochrane controlled trials register, Embase, and Medline. Data abstraction Two independent investigators identified studies on the clinical effects of statins compared with a placebo or control group and with follow-up of at least one year, at least 80% or more participants without established cardiovascular disease, and outcome data on mortality and major cardiovascular disease events. Heterogeneity was assessed using the Q and I(2) statistics. Publication bias was assessed by visual examination of funnel plots and the Egger regression test. RESULTS 10 trials enrolled a total of 70 388 people, of whom 23 681 (34%) were women and 16 078 (23%) had diabetes mellitus. Mean follow-up was 4.1 years. Treatment with statins significantly reduced the risk of all cause mortality (odds ratio 0.88, 95% confidence interval 0.81 to 0.96), major coronary events (0.70, 0.61 to 0.81), and major cerebrovascular events (0.81, 0.71 to 0.93). No evidence of an increased risk of cancer was observed. There was no significant heterogeneity of the treatment effect in clinical subgroups. CONCLUSION In patients without established cardiovascular disease but with cardiovascular risk factors, statin use was associated with significantly improved survival and large reductions in the risk of major cardiovascular events.",
"title": "The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials"
},
{
"docid": "12770738",
"text": "BACKGROUND Questions remain as to whether higher levels of cardiorespiratory fitness, a measure of regular physical activity, are associated with lower risk of cardiovascular disease (CVD) mortality in overweight and obese individuals with diabetes. Our objective was to quantify the independent and joint relations of cardiorespiratory fitness (hereafter, fitness) and body mass index (BMI; calculated as weight in kilograms divided by the square of height in meters) with CVD mortality in men with diabetes. METHODS This study was conducted using prospective observational data from the Aerobics Center Longitudinal Study. Study participants comprised 2316 men with no history of stroke or myocardial infarction and who were diagnosed as having diabetes (mean [SD] age, 50 [10] years); had a medical examination, including a maximal exercise test during 1970 to 1997 with mortality surveillance to December 31, 1998; and had a BMI of 18.5 or greater and less than 35.0. The main outcome measure was CVD mortality across levels of fitness with stratification by BMI. RESULTS We identified 179 CVD deaths during a mean (SD) follow-up of 15.9 (7.9) years and 36,710 man-years of exposure. In a model containing age, examination year, fasting glucose level, systolic blood pressure, parental history of premature CVD, total cholesterol level, cigarette smoking, abnormal resting, and exercise electrocardiograms, a significantly higher adjusted risk of mortality was observed in men with a low fitness level who were normal weight (hazard ratio, 2.7 [95% confidence interval, 1.3-5.7]), overweight (hazard ratio, 2.7 [95% confidence interval, 1.4-5.1]), and class 1 obese (hazard ratio, 2.8 [95% confidence interval, 1.4-5.1]) compared with normal weight men with a high fitness level. CONCLUSION In this cohort of men with diabetes, low fitness level was associated with increased risk of CVD mortality within normal weight, overweight, and class 1 obese weight categories.",
"title": "Cardiorespiratory fitness and body mass index as predictors of cardiovascular disease mortality among men with diabetes."
},
{
"docid": "8780599",
"text": "OBJECTIVE Although the Polypill concept (proposed in 2003) is promising in terms of benefits for cardiovascular risk management, the potential costs and adverse effects are its main pitfalls. The objective of this study was to identify a tastier and safer alternative to the Polypill: the Polymeal. METHODS Data on the ingredients of the Polymeal were taken from the literature. The evidence based recipe included wine, fish, dark chocolate, fruits, vegetables, garlic, and almonds. Data from the Framingham heart study and the Framingham offspring study were used to build life tables to model the benefits of the Polymeal in the general population from age 50, assuming multiplicative correlations. RESULTS Combining the ingredients of the Polymeal would reduce cardiovascular disease events by 76%. For men, taking the Polymeal daily represented an increase in total life expectancy of 6.6 years, an increase in life expectancy free from cardiovascular disease of 9.0 years, and a decrease in life expectancy with cardiovascular disease of 2.4 years. The corresponding differences for women were 4.8, 8.1, and 3.3 years. CONCLUSION The Polymeal promises to be an effective, non-pharmacological, safe, cheap, and tasty alternative to reduce cardiovascular morbidity and increase life expectancy in the general population.",
"title": "The Polymeal: a more natural, safer, and probably tastier (than the Polypill) strategy to reduce cardiovascular disease by more than 75%."
},
{
"docid": "21003930",
"text": "BACKGROUND Long-term exposure to pollution can lead to an increase in the rate of decline of lung function, especially in older individuals and in those with chronic obstructive pulmonary disease (COPD), whereas shorter-term exposure at higher pollution levels has been implicated in causing excess deaths from ischaemic heart disease and exacerbations of COPD. We aimed to assess the effects on respiratory and cardiovascular responses of walking down a busy street with high levels of pollution compared with walking in a traffic-free area with lower pollution levels in older adults. METHODS In this randomised, crossover study, we recruited men and women aged 60 years and older with angiographically proven stable ischaemic heart disease or stage 2 Global initiative for Obstructive Lung Disease (GOLD) COPD who had been clinically stable for 6 months, and age-matched healthy volunteers. Individuals with ischaemic heart disease or COPD were recruited from existing databases or outpatient respiratory and cardiology clinics at the Royal Brompton & Harefield NHS Foundation Trust and age-matched healthy volunteers using advertising and existing databases. All participants had abstained from smoking for at least 12 months and medications were taken as recommended by participants' doctors during the study. Participants were randomly assigned by drawing numbered disks at random from a bag to do a 2 h walk either along a commercial street in London (Oxford Street) or in an urban park (Hyde Park). Baseline measurements of participants were taken before the walk in the hospital laboratory. During each walk session, black carbon, particulate matter (PM) concentrations, ultrafine particles, and nitrogen dioxide (NO2) concentrations were measured. FINDINGS Between October, 2012, and June, 2014, we screened 135 participants, of whom 40 healthy volunteers, 40 individuals with COPD, and 39 with ischaemic heart disease were recruited. Concentrations of black carbon, NO2, PM10, PM2.5, and ultrafine particles were higher on Oxford Street than in Hyde Park. Participants with COPD reported more cough (odds ratio [OR] 1·95, 95% CI 0·96-3·95; p<0·1), sputum (3·15, 1·39-7·13; p<0·05), shortness of breath (1·86, 0·97-3·57; p<0·1), and wheeze (4·00, 1·52-10·50; p<0·05) after walking down Oxford Street compared with Hyde Park. In all participants, irrespective of their disease status, walking in Hyde Park led to an increase in lung function (forced expiratory volume in the first second [FEV1] and forced vital capacity [FVC]) and a decrease in pulse wave velocity (PWV) and augmentation index up to 26 h after the walk. By contrast, these beneficial responses were attenuated after walking on Oxford Street. In participants with COPD, a reduction in FEV1 and FVC, and an increase in R5-20 were associated with an increase in during-walk exposure to NO2, ultrafine particles and PM2.5, and an increase in PWV and augmentation index with NO2 and ultrafine particles. In healthy volunteers, PWV and augmentation index were associated both with black carbon and ultrafine particles. INTERPRETATION Short-term exposure to traffic pollution prevents the beneficial cardiopulmonary effects of walking in people with COPD, ischaemic heart disease, and those free from chronic cardiopulmonary diseases. Medication use might reduce the adverse effects of air pollution in individuals with ischaemic heart disease. Policies should aim to control ambient levels of air pollution along busy streets in view of these negative health effects. FUNDING British Heart Foundation.",
"title": "Respiratory and cardiovascular responses to walking down a traffic-polluted road compared with walking in a traffic-free area in participants aged 60 years and older with chronic lung or heart disease and age-matched healthy controls: a randomised, crossover study"
},
{
"docid": "39368721",
"text": "OBJECTIVE to investigate the role of glucose tolerance in the development of hypertension. DESIGN Retrospective analysis of the results of a health check up in a group of clinically healthy middle aged men in the late 1960s (median year 1968). The subjects were invited to enter into a primary prevention trial for cardiovascular disease in 1974, when they underwent clinical examination for risk factors. The trial was completed in 1979, when the men were re-examined. Follow up was in 1986. SETTING Institute of Occupational Health, Helsinki, Finland and second department of medicine, University of Helsinki. SUBJECTS In all, 3490 men born during 1919-34 participated in a health check up in the late 1960s. In 1974, 1815 of these men who were clinically healthy were entered into a primary prevention trial for cardiovascular disease. On clinical examination 1222 of the men were considered at high risk of cardiovascular disease. Of these, 612 received an intervention and were excluded from the study. A total of 593 men were without risk factors. The study comprised all of the men who did not have an intervention (n = 1203). In 1979, 1120 men were re-examined, and in 1986 945 men attended follow up. There were two groups for analysis: one comprising all subjects and the other comprising only men who were normotensive in 1968 and for whom complete information was available. INTERVENTIONS By 1979, 103 men were taking antihypertensive drugs, and by 1986, 131 were taking antihypertensive drugs and 12 were taking drugs for hyperglycaemia. MAIN OUTCOME MEASURES Blood glucose concentration one hour after a glucose load, blood pressure, and body weight were measured in 1968, 1974, and 1979. In 1986 blood pressure and body weight were recorded. RESULTS Men who were hypertensive in 1986 had significantly higher blood pressures (p less than 0.0001) and (after adjustment for body mass index and alcohol intake) significantly higher blood glucose concentrations one hour after a glucose load at all examinations than those who were normotensive in 1986. Regression analysis showed that the higher the blood glucose concentration after a glucose load in 1968 the higher the blood pressure during the following years. Those men between the second and third tertiles of blood glucose concentration in 1968 had a significantly higher risk of developing hypertension (odds ratio 1.71, 95% confidence interval 1.05 to 2.77) compared with those below the first tertile. CONCLUSION In this study men who developed hypertension tended to have shown an increased intolerance to glucose up to 18 years before the clinical manifestation of their disorder. Blood glucose concentration one hour after a glucose load was an independent predictor of future hypertension.",
"title": "Glucose tolerance and blood pressure: long term follow up in middle aged men."
},
{
"docid": "12794099",
"text": "BACKGROUND There is overwhelming evidence that behavioural factors influence health, but their combined impact on the general population is less well documented. We aimed to quantify the potential combined impact of four health behaviours on mortality in men and women living in the general community. METHODS AND FINDINGS We examined the prospective relationship between lifestyle and mortality in a prospective population study of 20,244 men and women aged 45-79 y with no known cardiovascular disease or cancer at baseline survey in 1993-1997, living in the general community in the United Kingdom, and followed up to 2006. Participants scored one point for each health behaviour: current non-smoking, not physically inactive, moderate alcohol intake (1-14 units a week) and plasma vitamin C >50 mmol/l indicating fruit and vegetable intake of at least five servings a day, for a total score ranging from zero to four. After an average 11 y follow-up, the age-, sex-, body mass-, and social class-adjusted relative risks (95% confidence intervals) for all-cause mortality(1,987 deaths) for men and women who had three, two, one, and zero compared to four health behaviours were respectively, 1.39 (1.21-1.60), 1.95 (1.70--2.25), 2.52 (2.13-3.00), and 4.04 (2.95-5.54) p < 0.001 trend. The relationships were consistent in subgroups stratified by sex, age, body mass index, and social class, and after excluding deaths within 2 y. The trends were strongest for cardiovascular causes. The mortality risk for those with four compared to zero health behaviours was equivalent to being 14 y younger in chronological age. CONCLUSIONS Four health behaviours combined predict a 4-fold difference in total mortality in men and women, with an estimated impact equivalent to 14 y in chronological age.",
"title": "Combined Impact of Health Behaviours and Mortality in Men and Women: The EPIC-Norfolk Prospective Population Study"
},
{
"docid": "27466734",
"text": "Objectives To develop and validate updated QRISK3 prediction algorithms to estimate the 10 year risk of cardiovascular disease in women and men accounting for potential new risk factors. Design Prospective open cohort study. Setting General practices in England providing data for the QResearch database. Participants 1309 QResearch general practices in England: 981 practices were used to develop the scores and a separate set of 328 practices were used to validate the scores. 7.89 million patients aged 25-84 years were in the derivation cohort and 2.67 million patients in the validation cohort. Patients were free of cardiovascular disease and not prescribed statins at baseline. Methods Cox proportional hazards models in the derivation cohort to derive separate risk equations in men and women for evaluation at 10 years. Risk factors considered included those already in QRISK2 (age, ethnicity, deprivation, systolic blood pressure, body mass index, total cholesterol: high density lipoprotein cholesterol ratio, smoking, family history of coronary heart disease in a first degree relative aged less than 60 years, type 1 diabetes, type 2 diabetes, treated hypertension, rheumatoid arthritis, atrial fibrillation, chronic kidney disease (stage 4 or 5)) and new risk factors (chronic kidney disease (stage 3, 4, or 5), a measure of systolic blood pressure variability (standard deviation of repeated measures), migraine, corticosteroids, systemic lupus erythematosus (SLE), atypical antipsychotics, severe mental illness, and HIV/AIDs). We also considered erectile dysfunction diagnosis or treatment in men. Measures of calibration and discrimination were determined in the validation cohort for men and women separately and for individual subgroups by age group, ethnicity, and baseline disease status. Main outcome measures Incident cardiovascular disease recorded on any of the following three linked data sources: general practice, mortality, or hospital admission records. Results 363 565 incident cases of cardiovascular disease were identified in the derivation cohort during follow-up arising from 50.8 million person years of observation. All new risk factors considered met the model inclusion criteria except for HIV/AIDS, which was not statistically significant. The models had good calibration and high levels of explained variation and discrimination. In women, the algorithm explained 59.6% of the variation in time to diagnosis of cardiovascular disease (R2, with higher values indicating more variation), and the D statistic was 2.48 and Harrell's C statistic was 0.88 (both measures of discrimination, with higher values indicating better discrimination). The corresponding values for men were 54.8%, 2.26, and 0.86. Overall performance of the updated QRISK3 algorithms was similar to the QRISK2 algorithms. Conclusion Updated QRISK3 risk prediction models were developed and validated. The inclusion of additional clinical variables in QRISK3 (chronic kidney disease, a measure of systolic blood pressure variability (standard deviation of repeated measures), migraine, corticosteroids, SLE, atypical antipsychotics, severe mental illness, and erectile dysfunction) can help enable doctors to identify those at most risk of heart disease and stroke.",
"title": "Development and validation of QRISK3 risk prediction algorithms to estimate future risk of cardiovascular disease: prospective cohort study"
},
{
"docid": "12561083",
"text": "BACKGROUND Several studies have demonstrated that women with nonobstructive coronary disease have a high rate of subsequent investigations, rehospitalizations for recurrent chest pain, and repeat coronary angiography. The sex specificity of this finding is unclear. We therefore undertook an evaluation of sex differences in rehospitalization for acute coronary syndrome (ACS) or chest pain in patients with \"angiographically normal\" coronaries. METHODS A retrospective cohort study using prospectively collected angiographic and clinical data on all patients in British Columbia, Canada, presenting for their first cardiac catheterization with suspected ischemic heart disease but angiographically normal coronaries. RESULTS Among 32,856 patients, 7.1% of men versus 23.3% of women were angiographically normal (P < .001). Among angiographically normal patients, women were older and more likely to present with hypertension, prior stroke, chronic obstructive pulmonary disease, and peripheral vascular disease than men, but Canadian Cardiovascular Society class of angina did not vary by sex. Within 1 year, 1.0% died, (19 women, 18 men, P = .27) and 0.6% had a stroke (13 women, 9 men, P = .91). Readmission to hospital for ACS or chest pain requiring catheterization was significantly higher in women compared to men (adjusted OR 4.06; 95% CI 1.15-14.31). CONCLUSIONS In a contemporary, population-based cohort presenting for cardiac catheterization for suspected ischemia, women with angiographically normal coronaries were >4 times more likely to be readmitted to hospital for ACS/chest pain within 180 days compared to men. The observed sex difference has important social and economic implications and suggests that traditional diagnostic methods may not be optimal for women.",
"title": "Angina with \"normal\" coronary arteries: sex differences in outcomes."
},
{
"docid": "11630388",
"text": "BACKGROUND Obesity is associated with diverse health risks, but the role of body weight as a risk factor for death remains controversial. METHODS We examined the association between body weight and the risk of death in a 12-year prospective cohort study of 1,213,829 Koreans between the ages of 30 and 95 years. We examined 82,372 deaths from any cause and 48,731 deaths from specific diseases (including 29,123 from cancer, 16,426 from atherosclerotic cardiovascular disease, and 3362 from respiratory disease) in relation to the body-mass index (BMI) (the weight in kilograms divided by the square of the height in meters). RESULTS In both sexes, the average baseline BMI was 23.2, and the rate of death from any cause had a J-shaped association with the BMI, regardless of cigarette-smoking history. The risk of death from any cause was lowest among patients with a BMI of 23.0 to 24.9. In all groups, the risk of death from respiratory causes was higher among subjects with a lower BMI, and the risk of death from atherosclerotic cardiovascular disease or cancer was higher among subjects with a higher BMI. The relative risk of death associated with BMI declined with increasing age. CONCLUSIONS Underweight, overweight, and obese men and women had higher rates of death than men and women of normal weight. The association of BMI with death varied according to the cause of death and was modified by age, sex, and smoking history.",
"title": "Body-mass index and mortality in Korean men and women."
},
{
"docid": "15984735",
"text": "OBJECTIVE To evaluate the association between migraine and cardiovascular disease, including stroke, myocardial infarction, and death due to cardiovascular disease. DESIGN Systematic review and meta-analysis. DATA SOURCES Electronic databases (PubMed, Embase, Cochrane Library) and reference lists of included studies and reviews published until January 2009. Selection criteria Case-control and cohort studies investigating the association between any migraine or specific migraine subtypes and cardiovascular disease. Review methods Two investigators independently assessed eligibility of identified studies in a two step approach. Disagreements were resolved by consensus. Studies were grouped according to a priori categories on migraine and cardiovascular disease. DATA EXTRACTION Two investigators extracted data. Pooled relative risks and 95% confidence intervals were calculated. RESULTS Studies were heterogeneous for participant characteristics and definition of cardiovascular disease. Nine studies investigated the association between any migraine and ischaemic stroke (pooled relative risk 1.73, 95% confidence interval 1.31 to 2.29). Additional analyses indicated a significantly higher risk among people who had migraine with aura (2.16, 1.53 to 3.03) compared with people who had migraine without aura (1.23, 0.90 to 1.69; meta-regression for aura status P=0.02). Furthermore, results suggested a greater risk among women (2.08, 1.13 to 3.84) compared with men (1.37, 0.89 to 2.11). Age less than 45 years, smoking, and oral contraceptive use further increased the risk. Eight studies investigated the association between migraine and myocardial infarction (1.12, 0.95 to 1.32) and five between migraine and death due to cardiovascular disease (1.03, 0.79 to 1.34). Only one study investigated the association between women who had migraine with aura and myocardial infarction and death due to cardiovascular disease, showing a twofold increased risk. CONCLUSION Migraine is associated with a twofold increased risk of ischaemic stroke, which is only apparent among people who have migraine with aura. Our results also suggest a higher risk among women and risk was further magnified for people with migraine who were aged less than 45, smokers, and women who used oral contraceptives. We did not find an overall association between any migraine and myocardial infarction or death due to cardiovascular disease. Too few studies are available to reliably evaluate the impact of modifying factors, such as migraine aura, on these associations.",
"title": "Migraine and cardiovascular disease: systematic review and meta-analysis."
},
{
"docid": "25355575",
"text": "Since the beginning of the 1990s the public health situation in Russia has been characterized by an extremely high mortality and a significant reduction in life expectancy. Cardiovascular diseases remained the major cause of death. Only a few large population studies were conducted in Russia during this period. A total of 1968 men and 1737 women aged 18–75 years participated in a health survey in Arkhangelsk, Russia, over the period 1999–2000. Investigation included assessment of classic cardiovascular risk factors (family history, smoking, blood pressure, and blood lipids) along with general health variables. The paper presents sex specific data on risk factors for coronary heart disease. Though the cardiovascular mortality is high in Russia, the calculated risk for coronary heart disease (the Framingham risk score and the Norwegian risk score) was lower in all age groups of men and women in Arkhangelsk compared with studies from the Western Europe and USA. Our data suggest that high cardiovascular mortality in Russia may be driven not only by the classic risk factors for coronary heart disease.",
"title": "High cardiovascular mortality in Russia cannot be explained by the classical risk factors. The Arkhangelsk study 2000"
},
{
"docid": "752423",
"text": "BACKGROUND A reduction in compliance of the large-sized cardiothoracic (central) arteries is an independent risk factor for the development of cardiovascular disease with advancing age. METHODS AND RESULTS We determined the role of habitual exercise on the age-related decrease in central arterial compliance by using both cross-sectional and interventional approaches. First, we studied 151 healthy men aged 18 to 77 years: 54 were sedentary, 45 were recreationally active, and 53 were endurance exercise-trained. Central arterial compliance (simultaneous B-mode ultrasound and arterial applanation tonometry on the common carotid artery) was lower (P:<0.05) in middle-aged and older men than in young men in all 3 groups. There were no significant differences between sedentary and recreationally active men at any age. However, arterial compliance in the endurance-trained middle-aged and older men was 20% to 35% higher than in the 2 less active groups (P:<0.01). As such, age-related differences in central arterial compliance were smaller in the endurance-trained men than in the sedentary and recreationally active men. Second, we studied 20 middle-aged and older (53+/-2 years) sedentary healthy men before and after a 3-month aerobic exercise intervention (primarily walking). Regular exercise increased central arterial compliance (P:<0.01) to levels similar to those of the middle-aged and older endurance-trained men. These effects were independent of changes in body mass, adiposity, arterial blood pressure, or maximal oxygen consumption. CONCLUSIONS Regular aerobic-endurance exercise attenuates age-related reductions in central arterial compliance and restores levels in previously sedentary healthy middle-aged and older men. This may be one mechanism by which habitual exercise lowers the risk of cardiovascular disease in this population.",
"title": "Aging, habitual exercise, and dynamic arterial compliance."
},
{
"docid": "75636923",
"text": "Metabolic syndrome is diagnosed when three or more of the following criteria are met: abdominal obesity (waist circumference more than 102 cm in men and 88 cm in women); hypertriglyceridemia of 150 mg/dl or above; a high-density lipoprotein (HDL) cholesterol level less than 40 mg/dl in men or 50 mg/dl in women; blood pressure of 130/85 mm Hg or higher; or fasting glucose of at least 110 mg/dl. Individuals with metabolic syndrome are likelier than others to develop diabetes and cardiovascular disease and have increased mortality from all causes (and from cardiovascular disease in particular). The investigators attempted to determine the prevalence of the syndrome in the United States by analyzing data on 8814 men and women 20 years of age or older who took part in the Third National Health and Nutrition Examination Survey in the years 1988 to 1994. This is a cross-sectional health survey of a sample of the noninstitutionalized civilian American population. The overall age-adjusted prevalence of metabolic syndrome was 23.7%. The prevalence rose from 6.7% in persons 20 to 29 years of age to 42% in those aged 70 years and more. There was virtually no gender-related difference in prevalence rates for the combined racial groups. Metabolic syndrome was most prevalent in Mexican Americans and least prevalent in whites, African Americans, and \"others. \" Among both African Americans and Mexican Americans, women had higher prevalence rates than men. Extrapolating from age-specific prevalence rates and US census counts from the year 2000, 47 million US residents have metabolic syndrome. Considering its prevalence, it seems important to estimate the direct medical costs of metabolic syndrome. In the great majority of cases the critical causes are improper nutrition and insufficient physical activity, emphasizing the importance of controlling obesity and encouraging physical activity in the United States.",
"title": "Prevalence of the Metabolic Syndrome Among Us Adults: Findings From the Third National Health and Nutrition Examination Survey"
},
{
"docid": "3413083",
"text": "BACKGROUND Following widespread rollout of chlamydia testing to non-specialist and community settings in the UK, many individuals receive a chlamydia test without being offered comprehensive STI and HIV testing. We assess sexual behaviour among testers in different settings with a view to understanding their need for other STI diagnostic services. METHODS A probability sample survey of the British population undertaken 2010-2012 (the third National Survey of Sexual Attitudes and Lifestyles). We analysed weighted data on chlamydia testing (past year), including location of most recent test, and diagnoses (past 5 years) from individuals aged 16-44 years reporting at least one sexual partner in the past year (4992 women, 3406 men). RESULTS Of the 26.8% (95% CI 25.4% to 28.2%) of women and 16.7% (15.5% to 18.1%) of men reporting a chlamydia test in the past year, 28.4% of women and 41.2% of men had tested in genitourinary medicine (GUM), 41.1% and 20.7% of women and men respectively tested in general practice (GP) and the remainder tested in other non-GUM settings. Women tested outside GUM were more likely to be older, in a relationship and to live in rural areas. Individuals tested outside GUM reported fewer risk behaviours; nevertheless, 11.0% (8.6% to 14.1%) of women and 6.8% (3.9% to 11.6%) of men tested in GP and 13.2% (10.2% to 16.8%) and 9.6% (6.5% to 13.8%) of women and men tested in other non-GUM settings reported 'unsafe sex', defined as two or more partners and no condom use with any partner in the past year. Individuals treated for chlamydia outside GUM in the past 5 years were less likely to report an HIV test in that time frame (women: 54.5% (42.7% to 65.7%) vs 74.1% (65.9% to 80.9%) in GUM; men: 23.9% (12.7% to 40.5%) vs 65.8% (56.2% to 74.3%)). CONCLUSIONS Most chlamydia testing occurred in non-GUM settings, among populations reporting fewer risk behaviours. However, there is a need to provide pathways to comprehensive STI care to the sizeable minority at higher risk.",
"title": "Patterns of chlamydia testing in different settings and implications for wider STI diagnosis and care: a probability sample survey of the British population"
},
{
"docid": "17124832",
"text": "CONTEXT Previous studies indicate that the population attributable risk (PAR) of bladder cancer for tobacco smoking is 50% to 65% in men and 20% to 30% in women and that current cigarette smoking triples bladder cancer risk relative to never smoking. During the last 30 years, incidence rates have remained stable in the United States in men (123.8 per 100,000 person-years to 142.2 per 100,000 person-years) and women (32.5 per 100,000 person-years to 33.2 per 100,000 person-years); however, changing smoking prevalence and cigarette composition warrant revisiting risk estimates for smoking and bladder cancer. OBJECTIVE To evaluate the association between tobacco smoking and bladder cancer. DESIGN, SETTING, AND PARTICIPANTS Men (n = 281,394) and women (n = 186,134) of the National Institutes of Health-AARP (NIH-AARP) Diet and Health Study cohort completed a lifestyle questionnaire and were followed up between October 25, 1995, and December 31, 2006. Previous prospective cohort studies of smoking and incident bladder cancer were identified by systematic review and relative risks were estimated from fixed-effects models with heterogeneity assessed by the I(2) statistic. MAIN OUTCOME MEASURES Hazard ratios (HRs), PARs, and number needed to harm (NNH). RESULTS During 4,518,941 person-years of follow-up, incident bladder cancer occurred in 3896 men (144.0 per 100,000 person-years) and 627 women (34.5 per 100,000 person-years). Former smokers (119.8 per 100,000 person-years; HR, 2.22; 95% confidence interval [CI], 2.03-2.44; NNH, 1250) and current smokers (177.3 per 100,000 person-years; HR, 4.06; 95% CI, 3.66-4.50; NNH, 727) had higher risks of bladder cancer than never smokers (39.8 per 100,000 person-years). In contrast, the summary risk estimate for current smoking in 7 previous studies (initiated between 1963 and 1987) was 2.94 (95% CI, 2.45-3.54; I(2) = 0.0%). The PAR for ever smoking in our study was 0.50 (95% CI, 0.45-0.54) in men and 0.52 (95% CI, 0.45-0.59) in women. CONCLUSION Compared with a pooled estimate of US data from cohorts initiated between 1963 and 1987, relative risks for smoking in the more recent NIH-AARP Diet and Health Study cohort were higher, with PARs for women comparable with those for men.",
"title": "Association between smoking and risk of bladder cancer among men and women."
},
{
"docid": "1711571",
"text": "PURPOSE Patients with type 2 diabetes mellitus (T2DM) have an increased fracture risk despite having higher areal bone mineral density (aBMD). This study aimed to clarify the association between glycemic and insulin resistance status and bone microarchitecture, and whether pentosidine and bone turnover markers play any roles in the association. METHODS A total of 2012 community-dwelling men aged ≥65years completed baseline measurements of spine aBMD, fasting plasma glucose (FPG) and serum insulin, hemoglobin A1c (HbA1c), osteocalcin, type I procollagen N-terminal propeptide, type I collagen C-terminal crosslinking telopeptide, tartrate-resistant acid phosphatase isoenzyme 5b, pentosidine, height and weight and an interview regarding past disease history. Homeostasis model assessment-insulin resistance (HOMA-IR) was also calculated. T2DM was defined as physician-diagnosed middle age or elderly-onset diabetes mellitus, or according to biochemical test results. To evaluate bone microarchitecture, trabecular bone score (TBS) was calculated at the same vertebrae as those used for aBMD measurement. RESULTS After excluding participants who had a disease history and/or were taking medications affecting bone metabolism, 1683 men (age, 72.9±5.2years) were analyzed. Men with T2DM had significantly higher aBMD compared to those without T2DM. There was no significant difference in TBS. However, FPG, HbA1c and HOMA-IR levels were significantly inversely correlated with TBS after adjusting for age, BMI and aBMD. Multivariate linear regression analyses revealed that glycemic indices (FPG and HbA1c) were significantly associated with increased aBMD and decreased TBS, and that HOMA-IR was associated only with TBS. These associations did not change after further adjusting for bone turnover makers and pentosidine levels. CONCLUSIONS Hyperglycemia and elevated insulin-resistance were associated with low TBS independently of bone turnover and pentosidine levels.",
"title": "Hyperglycemia is associated with increased bone mineral density and decreased trabecular bone score in elderly Japanese men: The Fujiwara-kyo osteoporosis risk in men (FORMEN) study."
},
{
"docid": "409280",
"text": "BACKGROUND Few data have evaluated physician adherence to cardiovascular disease (CVD) prevention guidelines according to physician specialty or patient characteristics, particularly gender. METHODS AND RESULTS An online study of 500 randomly selected physicians (300 primary care physicians, 100 obstetricians/gynecologists, and 100 cardiologists) used a standardized questionnaire to assess awareness of, adoption of, and barriers to national CVD prevention guidelines by specialty. An experimental case study design tested physician accuracy and determinants of CVD risk level assignment and application of guidelines among high-, intermediate-, or low-risk patients. Intermediate-risk women, as assessed by the Framingham risk score, were significantly more likely to be assigned to a lower-risk category by primary care physicians than men with identical risk profiles (P<0.0001), and trends were similar for obstetricians/gynecologists and cardiologists. Assignment of risk level significantly predicted recommendations for lifestyle and preventive pharmacotherapy. After adjustment for risk assignment, the impact of patient gender on preventive care was not significant except for less aspirin (P<0.01) and more weight management recommended (P<0.04) for intermediate-risk women. Physicians did not rate themselves as very effective in their ability to help patients prevent CVD. Fewer than 1 in 5 physicians knew that more women than men die each year from CVD. CONCLUSIONS Perception of risk was the primary factor associated with CVD preventive recommendations. Gender disparities in recommendations for preventive therapy were explained largely by the lower perceived risk despite similar calculated risk for women versus men. Educational interventions for physicians are needed to improve the quality of CVD preventive care and lower morbidity and mortality from CVD for men and women.",
"title": "National study of physician awareness and adherence to cardiovascular disease prevention guidelines."
},
{
"docid": "5939172",
"text": "PURPOSE To analyze the relationship between an aspect of drinking pattern (i.e., drinking with or without meals) and risk of all-cause and specific-cause mortality. METHODS The Risk Factors and Life Expectancy Study, is a pooling of a series of epidemiological studies conducted in Italy. Eight-thousand six-hundred and forty-seven men and 6521 women, age 30-59 at baseline, and free of cardiovascular disease, were followed for mortality from all causes, cardiovascular and noncardiovascular, during an average follow-up of 7 years. RESULTS Drinkers of wine outside meals exhibited higher death rates from all causes, noncardiovascular diseases, and cancer, as compared to drinkers of wine with meals. This association was independent from the cardiovascular disease (CVD) risk factors measured at baseline and the amount of alcohol consumed and seemed to be stronger in women as compared to men. CONCLUSIONS The present results indicate that drinking patterns may have important health implications, and attention should be given to this aspect of alcohol use and its relationship to health outcomes. The relationship between alcohol consumption and disease has been the focus of intensive scientific investigation (1-9). Most studies to date, however, have limitations. A major drawback is that limited information has been collected regarding the complex issue of alcohol consumption. In many studies, ascertainment of alcohol consumption frequently focused only on quantity of alcohol consumed without considering the many different components of alcohol consumption, particularly drinking pattern (10-12). It has been hypothesized, and preliminary data support the notion, that drinking pattern could have important influences on determining the health effects of alcohol (13,14). The present study examines the relationship between one aspect of drinking pattern (drinking wine outside meals) and mortality in a large cohort of men and women.",
"title": "Drinking pattern and mortality: the Italian Risk Factor and Life Expectancy pooling project."
},
{
"docid": "23785605",
"text": "BACKGROUND Migraine, particularly with aura, is a risk factor for early-onset ischemic stroke. The underlying mechanisms are unknown, but may in part be due to migraineurs having an increased risk profile for cardiovascular disease. In this study, the authors compare the cardiovascular risk profile of adult migraineurs to that of nonmigraineurs. METHODS Participants (n = 5,755, 48% men, age 20 to 65 years) are from the Genetic Epidemiology of Migraine (GEM) study, a population-based study in the Netherlands. A total of 620 current migraineurs were identified: 31% with aura (MA), 64% without aura (MO), and 5% unclassified. Controls were 5,135 individuals without lifetime migraine. Measured cardiovascular risk factors included blood pressure (BP), serum total and high-density lipoprotein cholesterol (TC, HDL), smoking, oral contraceptive use, and the Framingham risk score for myocardial infarction or coronary heart disease (CHD) death. RESULTS Compared to controls, migraineurs were more likely to smoke (OR = 1.43 [1.1 to 1.8]), less likely to consume alcohol (OR = 0.58 [0.5 to 0.7]), and more likely to report a parental history of early myocardial infarction. Migraineurs with aura were more likely to have an unfavorable cholesterol profile (TC > or = 240 mg/dL [OR = 1.43 (0.97 to 2.1)], TC:HDL ratio > 5.0 [OR = 1.64 (1.1 to 2.4)]), have elevated BP (systolic BP > 140 mm Hg or diastolic BP > 90 mm Hg [OR = 1.76 (1.04 to 3.0)]), and report a history of early onset CHD or stroke (OR = 3.96 [1.1 to 14.3]); female migraineurs with aura were more likely to be using oral contraceptives (OR = 2.06 [1.05 to 4.0]). The odds of having an elevated Framingham risk score for CHD were approximately doubled for the migraineurs with aura. CONCLUSIONS Migraineurs, particularly with aura, have a higher cardiovascular risk profile than individuals without migraine.",
"title": "Cardiovascular risk factors and migraine: the GEM population-based study."
},
{
"docid": "43629704",
"text": "BACKGROUND Lowering the blood cholesterol level may reduce the risk of coronary heart disease. This double-blind study was designed to determine whether the administration of pravastatin to men with hypercholesterolemia and no history of myocardial infarction reduced the combined incidence of nonfatal myocardial infarction and death from coronary heart disease. METHODS We randomly assigned 6595 men, 45 to 64 years of age, with a mean (+/- SD) plasma cholesterol level of 272 +/- 23 mg per deciliter (7.0 +/- 0.6 mmol per liter) to receive pravastatin (40 mg each evening) or placebo. The average follow-up period was 4.9 years. Medical records, electrocardiographic recordings, and the national death registry were used to determine the clinical end points. RESULTS Pravastatin lowered plasma cholesterol levels by 20 percent and low-density-lipoprotein cholesterol levels by 26 percent, whereas there was no change with placebo. There were 248 definite coronary events (specified as nonfatal myocardial infarction or death from coronary heart disease) in the placebo group, and 174 in the pravastatin group (relative reduction in risk with pravastatin, 31 percent; 95 percent confidence interval, 17 to 43 percent; P < 0.001). There were similar reductions in the risk of definite nonfatal myocardial infarctions (31 percent reduction, P < 0.001), death from coronary heart disease (definite cases alone: 28 percent reduction, P = 0.13; definite plus suspected cases: 33 percent reduction, P = 0.042), and death from all cardiovascular causes (32 percent reduction, P = 0.033). There was no excess of deaths from noncardiovascular causes in the pravastatin group. We observed a 22 percent reduction in the risk of death from any cause in the pravastatin group (95 percent confidence interval, 0 to 40 percent; P = 0.051). CONCLUSIONS Treatment with pravastatin significantly reduced the incidence of myocardial infarction and death from cardiovascular causes without adversely affecting the risk of death from noncardiovascular causes in men with moderate hypercholesterolemia and no history of myocardial infarction.",
"title": "Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group."
},
{
"docid": "18199839",
"text": "BACKGROUND Persistent inflammation has been proposed to contribute to various stages in the pathogenesis of cardiovascular disease. Interleukin-6 receptor (IL6R) signalling propagates downstream inflammation cascades. To assess whether this pathway is causally relevant to coronary heart disease, we studied a functional genetic variant known to affect IL6R signalling. METHODS In a collaborative meta-analysis, we studied Asp358Ala (rs2228145) in IL6R in relation to a panel of conventional risk factors and inflammation biomarkers in 125,222 participants. We also compared the frequency of Asp358Ala in 51,441 patients with coronary heart disease and in 136,226 controls. To gain insight into possible mechanisms, we assessed Asp358Ala in relation to localised gene expression and to postlipopolysaccharide stimulation of interleukin 6. FINDINGS The minor allele frequency of Asp358Ala was 39%. Asp358Ala was not associated with lipid concentrations, blood pressure, adiposity, dysglycaemia, or smoking (p value for association per minor allele ≥0·04 for each). By contrast, for every copy of 358Ala inherited, mean concentration of IL6R increased by 34·3% (95% CI 30·4-38·2) and of interleukin 6 by 14·6% (10·7-18·4), and mean concentration of C-reactive protein was reduced by 7·5% (5·9-9·1) and of fibrinogen by 1·0% (0·7-1·3). For every copy of 358Ala inherited, risk of coronary heart disease was reduced by 3·4% (1·8-5·0). Asp358Ala was not related to IL6R mRNA levels or interleukin-6 production in monocytes. INTERPRETATION Large-scale human genetic and biomarker data are consistent with a causal association between IL6R-related pathways and coronary heart disease. FUNDING British Heart Foundation; UK Medical Research Council; UK National Institute of Health Research, Cambridge Biomedical Research Centre; BUPA Foundation.",
"title": "Interleukin-6 receptor pathways in coronary heart disease: a collaborative meta-analysis of 82 studies"
},
{
"docid": "2052720",
"text": "OBJECTIVE To investigate the association between gastric cancer and prior infection with Helicobacter pylori. DESIGN Case-control comparison of prevalence of IgG antibodies to H pylori in blood samples collected prospectively, before diagnosis of gastric cancer in the cases. Presence of H pylori antibody (greater than 10 micrograms IgG/ml) determined by enzyme linked immunosorbent assay (ELISA). SUBJECTS 29 men with a subsequent diagnosis of gastric cancer and 116 aged matched controls selected from over 22,000 middle aged men participating in two ongoing cohort studies (the British United Provident Association study and the Caerphilly collaborative heart disease study), who had provided blood samples during 1975-1982. RESULTS 20 of the 29 cases (69%) and 54 of the 116 controls (47%) were positive for H pylori specific antibody. The median specific IgG concentration was significantly higher in the cases than controls (90 micrograms/ml v 3.6 micrograms/ml, p less than 0.01). The estimated odds ratio for the risk of gastric cancer in those with a history of infection with H pylori was 2.77 (95% confidence interval 1.04 to 7.97, 2p = 0.039). CONCLUSIONS H pylori infection may be an important cause of gastric cancer; between 35% and 55% of all cases may be associated with such an infection.",
"title": "Association between infection with Helicobacter pylori and risk of gastric cancer: evidence from a prospective investigation."
},
{
"docid": "15925931",
"text": "BACKGROUND Whole-body magnetic resonance angiography (WB-MRA) has shown its potential for the non-invasive assessment of nearly the entire arterial vasculature within one examination. Since the presence of extra-cardiac atherosclerosis is associated with an increased risk of coronary events, our goal was to establish the relationship between WB-MRA findings, including a systemic atherosclerosis score index, and the presence of significant coronary artery disease (CAD). METHODS WB-MRA was performed on a 1.5T scanner in 50 patients scheduled to undergo elective cardiac catheterization for suspected CAD. In each patient, 40 extra-cardiac vessel segments were evaluated and assigned scores according to their luminal narrowing. The atherosclerosis score index (ASI) was generated as the ratio of summed scores to analyzable segments. RESULTS ASI was higher in patients with significant (> 50% stenosis) CAD (n = 27) vs. patients without CAD (n = 22; 1.56 vs. 1.28, p = 0.004). ASI correlated with PROCAM (R = 0.57, p < 0.001) and Framingham (R = 0.36, p = 0.01) risk scores as estimates of the 10-year risk of coronary events. A ROC derived ASI of > 1.54 predicted significant CAD with a sensitivity of 59%, specificity of 86% and a positive predictive value of 84%. Logistic regression revealed ASI > 1.54 as the strongest independent predictor for CAD with a 11-fold increase in likelihood to suffer from significant coronary disease. On the contrary, while 15/27 (55%) of patients with CAD exhibited at least one extra-cardiac stenosis > 50%, only 3/22 (14%) of those patients without CAD did (p = 0.003). The likelihood for an extra-cardiac stenosis when CAD is present differed between vascular territories and ranged from 15% for a carotid stenosis to 44% for a stenosis in the lower extremities. CONCLUSION This study provides important new evidence for the close association of extra-cardiac and coronary atherosclerosis. The novel findings that a WB-MRA derived systemic atherosclerosis score index is not only associated with established cardiovascular risk scores but is also predictive of significant CAD suggest its potential prognostic implications and underline the importance to screen for coronary disease in patients with extra-cardiac manifestations of atherosclerosis.",
"title": "Prediction of coronary artery disease by a systemic atherosclerosis score index derived from whole-body MR angiography"
},
{
"docid": "16252863",
"text": "The list of preventable and reversible risk factors for atherosclerotic cardiovascular disease continues to grow. Cigarette smoking, high blood pressure, physical inactivity, elevated cholesterol, underlying lipoprotein abnormalities, lipoprotein(a), diabetes, overweight, male gender, and age are well-established risk factors. During the 1990s, there have been many reports associating elevated plasma homocysteine levels with arteriosclerotic cardiovascular disease and consistent evidence that dietary and supplemental folic acid can reduce homocysteine levels.1 2 The article by Robinson and colleagues3 in this issue of Circulation presents further evidence of the importance of homocysteine and suggestive evidence that plasma folate and plasma pyrixodal-l-phosphate (vitamin B6) are protective factors. Their study is part of the European Concerted Action Project,4 which examined 750 patients younger than age 60 with diagnoses within the previous 12 months of coronary, cerebrovascular, or peripheral vascular disease and 800 healthy control subjects. The patient groups were young (47 years for cases and 44 years for control subjects) and heterogeneous, with nonfatal clinical events or symptoms of arteriosclerotic cardiovascular disease supported by ECG, angiographic, or Doppler evidence; the study involved 19 centers in nine European countries. Men in the highest quintile for fasting total homocysteine (tHcy), compared with the remainder of the population, had an estimated relative risk of 2.2 (95% confidence interval [CI], 1.6 to 2.9), with a striking dose-response relationship and a more-than-multiplicative interaction with cigarette smoking and high blood pressure on vascular disease risk4 ; the corresponding estimated relative risk for coronary heart disease was similar (2.0; 95% CI 1.6 to 2.8). (tHcy is the sum of homocysteine and homocysteinyl moieties of oxidized disulfides, homocystine, and cysteine- homocysteine. ) Robinson and colleagues3 examined three B vitamins in detail to determine their effects on fasting and post–methionine-loading tHcy levels and any independent effects on cardiovascular disease …",
"title": "Preventing coronary heart disease: B vitamins and homocysteine."
},
{
"docid": "44624045",
"text": "BACKGROUND Few previous prospective studies have examined differences in incident ischemic heart disease (IHD) risk between vegetarians and nonvegetarians. OBJECTIVE The objective was to examine the association of a vegetarian diet with risk of incident (nonfatal and fatal) IHD. DESIGN A total of 44,561 men and women living in England and Scotland who were enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Oxford study, of whom 34% consumed a vegetarian diet at baseline, were part of the analysis. Incident cases of IHD were identified through linkage with hospital records and death certificates. Serum lipids and blood pressure measurements were available for 1519 non cases, who were matched to IHD cases by sex and age. IHD risk by vegetarian status was estimated by using multivariate Cox proportional hazards models. RESULTS After an average follow-up of 11.6 y, there were 1235 IHD cases (1066 hospital admissions and 169 deaths). Compared with nonvegetarians, vegetarians had a lower mean BMI [in kg/m(2); -1.2 (95% CI: -1.3, -1.1)], non-HDL-cholesterol concentration [-0.45 (95% CI: -0.60, -0.30) mmol/L], and systolic blood pressure [-3.3 (95% CI: -5.9, -0.7) mm Hg]. Vegetarians had a 32% lower risk (HR: 0.68; 95% CI: 0.58, 0.81) of IHD than did nonvegetarians, which was only slightly attenuated after adjustment for BMI and did not differ materially by sex, age, BMI, smoking, or the presence of IHD risk factors. CONCLUSION Consuming a vegetarian diet was associated with lower IHD risk, a finding that is probably mediated by differences in non-HDL cholesterol, and systolic blood pressure.",
"title": "Risk of hospitalization or death from ischemic heart disease among British vegetarians and nonvegetarians: results from the EPIC-Oxford cohort study."
},
{
"docid": "45027320",
"text": "BACKGROUND The aim of this study was to examine the clustering of four major lifestyle risk factors (smoking, heavy drinking, lack of fruit and vegetables consumption, and lack of physical activity), and to examine the variation across different socio-demographic groups in the English adult population. METHODS The study population was derived from the 2003 Health Survey for England (n=11,492). Clustering was examined by comparing the observed and expected prevalence of the different possible combinations. A multinomial multilevel regression model was conducted to examine the socio-demographic variation in the clustering of the four risk factors. RESULTS The study found that, when using British health recommendations, a majority of the English population have multiple lifestyle risk factors at the same time. Clustering was found at both ends of the lifestyle spectrum and was more pronounced for women than for men. Overall, multiple risk factors were more prevalent among men, lower social class households, singles, and people who are economically inactive, but less prevalent among home owners and older age groups. CONCLUSIONS The clustering of multiple risk factors provides support for multiple-behavior interventions as opposed to single-behavior interventions.",
"title": "The prevalence and clustering of four major lifestyle risk factors in an English adult population."
},
{
"docid": "6327940",
"text": "Amino acids modulate the secretion of both insulin and glucagon; the composition of dietary protein therefore has the potential to influence the balance of glucagon and insulin activity. Soy protein, as well as many other vegan proteins, are higher in non-essential amino acids than most animal-derived food proteins, and as a result should preferentially favor glucagon production. Acting on hepatocytes, glucagon promotes (and insulin inhibits) cAMP-dependent mechanisms that down-regulate lipogenic enzymes and cholesterol synthesis, while up-regulating hepatic LDL receptors and production of the IGF-I antagonist IGFBP-1. The insulin-sensitizing properties of many vegan diets--high in fiber, low in saturated fat--should amplify these effects by down-regulating insulin secretion. Additionally, the relatively low essential amino acid content of some vegan diets may decrease hepatic IGF-I synthesis. Thus, diets featuring vegan proteins can be expected to lower elevated serum lipid levels, promote weight loss, and decrease circulating IGF-I activity. The latter effect should impede cancer induction (as is seen in animal studies with soy protein), lessen neutrophil-mediated inflammatory damage, and slow growth and maturation in children. In fact, vegans tend to have low serum lipids, lean physiques, shorter stature, later puberty, and decreased risk for certain prominent 'Western' cancers; a vegan diet has documented clinical efficacy in rheumatoid arthritis. Low-fat vegan diets may be especially protective in regard to cancers linked to insulin resistance--namely, breast and colon cancer--as well as prostate cancer; conversely, the high IGF-I activity associated with heavy ingestion of animal products may be largely responsible for the epidemic of 'Western' cancers in wealthy societies. Increased phytochemical intake is also likely to contribute to the reduction of cancer risk in vegans. Regression of coronary stenoses has been documented during low-fat vegan diets coupled with exercise training; such regimens also tend to markedly improve diabetic control and lower elevated blood pressure. Risk of many other degenerative disorders may be decreased in vegans, although reduced growth factor activity may be responsible for an increased risk of hemorrhagic stroke. By altering the glucagon/insulin balance, it is conceivable that supplemental intakes of key non-essential amino acids could enable omnivores to enjoy some of the health advantages of a vegan diet. An unnecessarily high intake of essential amino acids--either in the absolute sense or relative to total dietary protein--may prove to be as grave a risk factor for 'Western' degenerative diseases as is excessive fat intake.",
"title": "Vegan proteins may reduce risk of cancer, obesity, and cardiovascular disease by promoting increased glucagon activity."
},
{
"docid": "5884524",
"text": "BACKGROUND Although unstable coronary artery disease is the most common reason for admission to a coronary care unit, the long-term prognosis of patients with this diagnosis is unknown. This is particularly true for patients with diabetes mellitus, who are known to have a high morbidity and mortality after an acute myocardial infarction. METHODS AND RESULTS Prospectively collected data from 6 different countries in the Organization to Assess Strategies for Ischemic Syndromes (OASIS) registry were analyzed to determine the 2-year prognosis of diabetic and nondiabetic patients who were hospitalized with unstable angina or non-Q-wave myocardial infarction. Overall, 1718 of 8013 registry patients (21%) had diabetes. Diabetic patients had a higher rate of coronary bypass surgery than nondiabetic patients (23% versus 20%, P:<0.001) but had similar rates of catheterization and angioplasty. Diabetes independently predicted mortality (relative risk [RR], 1.57; 95% CI, 1.38 to 1.81; P:<0.001), as well as cardiovascular death, new myocardial infarction, stroke, and new congestive heart failure. Moreover, compared with their nondiabetic counterparts, women had a significantly higher risk than men (RR, 1.98; 95% CI, 1.60 to 2.44; and RR, 1.28; 95% CI, 1.06 to 1.56, respectively). Interestingly, diabetic patients without prior cardiovascular disease had the same event rates for all outcomes as nondiabetic patients with previous vascular disease. CONCLUSIONS Hospitalization for unstable angina or non-Q-wave myocardial infarction predicts a high 2-year morbidity and mortality; this is especially evident for patients with diabetes. Diabetic patients with no previous cardiovascular disease have the same long-term morbidity and mortality as nondiabetic patients with established cardiovascular disease after hospitalization for unstable coronary artery disease.",
"title": "Impact of diabetes on long-term prognosis in patients with unstable angina and non-Q-wave myocardial infarction: results of the OASIS (Organization to Assess Strategies for Ischemic Syndromes) Registry."
},
{
"docid": "9617381",
"text": "OBJECTIVE To evaluate long-term prognostic effect of serum noncholesterol sterols, including plant sterols, in middle-aged men with high cardiovascular disease (CVD) risk, without statins at baseline. METHODS This was a prospective study of 232 men (mean age 60 years) at high risk of CVD in 1985-1986. Most were hypercholesterolemic, 29 (12%) had a history of CVD or cancer, 6 (3%) had diabetes, and 46 (20%) had metabolic syndrome (MS). Measured noncholesterol sterols (expressed as absolute concentrations or ratios to serum cholesterol to standardize for cholesterol concentrations) included lathosterol and desmosterol (reflect cholesterol synthesis), and plant sterols (campesterol and sitosterol) and cholestanol (reflect cholesterol absorption). Main outcome measure was total mortality. RESULTS At baseline, markers of cholesterol synthesis and absorption showed expected inverse associations. During the 22-year follow-up 101 men (43%) died. At baseline, nonsurvivors smoked more, exercised less and had more components of MS (although not filling strict criteria), whereas traditional risk factors of CVD were not significantly different. Of the noncholesterol sterols (either absolute or ratio), only sitosterol was significantly higher in survivors than in nonsurvivors (P=0.02). In multivariable analyses, highest sitosterol-to-cholesterol tertile was associated with significantly lower mortality risk (HR 0.51, 95% CI 0.30-0.87) as compared to lowest tertile. Other associations were nonsignificant, although a \"global\" index of cholesterol metabolism (desmosterol-to-sitosterol ratio) suggested higher cholesterol synthesis and lower absorption to be associated with higher total and CVD mortality. CONCLUSION Higher serum plant sterol levels in middle-aged men predicted lower long-term mortality risk, possibly reflecting an association between higher synthesis/lower absorption of cholesterol and mortality.",
"title": "Serum plant and other noncholesterol sterols, cholesterol metabolism and 22-year mortality among middle-aged men."
}
] |
69
|
Activation of PPM1D enhances p53 function.
|
[
{
"docid": "4414547",
"text": "Improved sequencing technologies offer unprecedented opportunities for investigating the role of rare genetic variation in common disease. However, there are considerable challenges with respect to study design, data analysis and replication. Using pooled next-generation sequencing of 507 genes implicated in the repair of DNA in 1,150 samples, an analytical strategy focused on protein-truncating variants (PTVs) and a large-scale sequencing case–control replication experiment in 13,642 individuals, here we show that rare PTVs in the p53-inducible protein phosphatase PPM1D are associated with predisposition to breast cancer and ovarian cancer. PPM1D PTV mutations were present in 25 out of 7,781 cases versus 1 out of 5,861 controls (P = 1.12 × 10−5), including 18 mutations in 6,912 individuals with breast cancer (P = 2.42 × 10−4) and 12 mutations in 1,121 individuals with ovarian cancer (P = 3.10 × 10−9). Notably, all of the identified PPM1D PTVs were mosaic in lymphocyte DNA and clustered within a 370-base-pair region in the final exon of the gene, carboxy-terminal to the phosphatase catalytic domain. Functional studies demonstrate that the mutations result in enhanced suppression of p53 in response to ionizing radiation exposure, suggesting that the mutant alleles encode hyperactive PPM1D isoforms. Thus, although the mutations cause premature protein truncation, they do not result in the simple loss-of-function effect typically associated with this class of variant, but instead probably have a gain-of-function effect. Our results have implications for the detection and management of breast and ovarian cancer risk. More generally, these data provide new insights into the role of rare and of mosaic genetic variants in common conditions, and the use of sequencing in their identification.",
"title": "Mosaic PPM1D mutations are associated with predisposition to breast and ovarian cancer"
},
{
"docid": "5956380",
"text": "Gliomas arising in the brainstem and thalamus are devastating tumors that are difficult to surgically resect. To determine the genetic and epigenetic landscape of these tumors, we performed exomic sequencing of 14 brainstem gliomas (BSGs) and 12 thalamic gliomas. We also performed targeted mutational analysis of an additional 24 such tumors and genome-wide methylation profiling of 45 gliomas. This study led to the discovery of tumor-specific mutations in PPM1D, encoding wild-type p53-induced protein phosphatase 1D (WIP1), in 37.5% of the BSGs that harbored hallmark H3F3A mutations encoding p. Lys27Met substitutions. PPM1D mutations were mutually exclusive with TP53 mutations in BSG and attenuated p53 activation in vitro. PPM1D mutations were truncating alterations in exon 6 that enhanced the ability of PPM1D to suppress the activation of the DNA damage response checkpoint protein CHK2. These results define PPM1D as a frequent target of somatic mutation and as a potential therapeutic target in brainstem gliomas.",
"title": "Exome sequencing identifies somatic gain-of-function PPM1D mutations in brainstem gliomas"
}
] |
[
{
"docid": "23985464",
"text": "Wild-type p53 has recently been shown to repress transcription from several cellular and viral promoters. Since p53 mutations are the most frequently reported genetic defects in human cancers, it becomes important to study the effects of mutations of p53 on promoter functions. We, therefore, have studied the effects of wild-type and mutant human p53 on the human proliferating-cell nuclear antigen (PCNA) promoter and on several viral promoters, including the herpes simplex virus type 1 UL9 promoter, the human cytomegalovirus major immediate-early promoter-enhancer, and the long terminal repeat promoters of Rous sarcoma virus and human T-cell lymphotropic virus type I. HeLa cells were cotransfected with a wild-type or mutant p53 expression vector and a plasmid containing a chloramphenicol acetyltransferase reporter gene under viral (or cellular) promoter control. As expected, expression of the wild-type p53 inhibited promoter function. Expression of a p53 with a mutation at any one of the four amino acid positions 175, 248, 273, or 281, however, correlated with a significant increase of the PCNA promoter activity (2- to 11-fold). The viral promoters were also activated, although to a somewhat lesser extent. We also showed that activation by a mutant p53 requires a minimal promoter containing a lone TATA box. A more significant increase (25-fold) in activation occurs when the promoter contains a binding site for the activating transcription factor or cyclic AMP response element-binding protein. Using Saos-2 cells that do not express p53, we showed that activation by a mutant p53 was a direct enhancement. The mutant forms of p53 used in this study are found in various cancer cells. The activation of PCNA by mutant p53s may indicate a way to increase cell proliferation by the mutant p53s. Thus, our data indicate a possible functional role for the mutants of p53 found in cancer cells in activating several important loci, including PCNA.",
"title": "Modulation of cellular and viral promoters by mutant human p53 proteins found in tumor cells."
},
{
"docid": "21307488",
"text": "HER-2/neu amplification or overexpression can make cancer cells resistant to apoptosis and promotes their growth. p53 is crucial in regulating cell growth and apoptosis, and is often mutated or deleted in many types of tumour. Moreover, many tumours with a wild-type gene for p53 do not have normal p53 function, suggesting that some oncogenic signals suppress the function of p53. In this study, we show that HER-2/neu-mediated resistance to DNA-damaging agents requires the activation of Akt, which enhances MDM2-mediated ubiquitination and degradation of p53. Akt physically associates with MDM2 and phosphorylates it at Ser166 and Ser186. Phosphorylation of MDM2 enhances its nuclear localization and its interaction with p300, and inhibits its interaction with p19ARF, thus increasing p53 degradation. Our study indicates that blocking the Akt pathway mediated by HER-2/neu would increase the cytotoxic effect of DNA-damaging drugs in tumour cells with wild-type p53.",
"title": "HER-2/neu induces p53 ubiquitination via Akt-mediated MDM2 phosphorylation"
},
{
"docid": "9669099",
"text": "Binding within or nearby target genes involved in cell proliferation and survival enables the p53 tumor suppressor gene to regulate their transcription and cell-cycle progression. Using genome-wide chromatin-binding profiles, we describe binding of p53 also to regions located distantly from any known p53 target gene. Interestingly, many of these regions possess conserved p53-binding sites and all known hallmarks of enhancer regions. We demonstrate that these p53-bound enhancer regions (p53BERs) indeed contain enhancer activity and interact intrachromosomally with multiple neighboring genes to convey long-distance p53-dependent transcription regulation. Furthermore, p53BERs produce, in a p53-dependent manner, enhancer RNAs (eRNAs) that are required for efficient transcriptional enhancement of interacting target genes and induction of a p53-dependent cell-cycle arrest. Thus, our results ascribe transcription enhancement activity to p53 with the capacity to regulate multiple genes from a single genomic binding site. Moreover, eRNA production from p53BERs is required for efficient p53 transcription enhancement.",
"title": "eRNAs are required for p53-dependent enhancer activity and gene transcription."
},
{
"docid": "37204802",
"text": "Jumonji domain-containing 6 (JMJD6) is a member of the Jumonji C domain-containing family of proteins. Compared to other members of the family, the cellular activity of JMJD6 is still not clearly defined and its biological function is still largely unexplored. Here we report that JMJD6 is physically associated with the tumor suppressor p53. We demonstrated that JMJD6 acts as an α-ketoglutarate- and Fe(II)-dependent lysyl hydroxylase to catalyze p53 hydroxylation. We found that p53 indeed exists as a hydroxylated protein in vivo and that the hydroxylation occurs mainly on lysine 382 of p53. We showed that JMJD6 antagonizes p53 acetylation, promotes the association of p53 with its negative regulator MDMX, and represses transcriptional activity of p53. Depletion of JMJD6 enhances p53 transcriptional activity, arrests cells in the G1 phase, promotes cell apoptosis, and sensitizes cells to DNA damaging agent-induced cell death. Importantly, knockdown of JMJD6 represses p53-dependent colon cell proliferation and tumorigenesis in vivo, and significantly, the expression of JMJD6 is markedly up-regulated in various types of human cancer especially in colon cancer, and high nuclear JMJD6 protein is strongly correlated with aggressive clinical behaviors of colon adenocarcinomas. Our results reveal a novel posttranslational modification for p53 and support the pursuit of JMJD6 as a potential biomarker for colon cancer aggressiveness and a potential target for colon cancer intervention.",
"title": "JMJD6 Promotes Colon Carcinogenesis through Negative Regulation of p53 by Hydroxylation"
},
{
"docid": "14460402",
"text": "The molecular mechanisms that regulate adult neural precursor cell (NPC) survival, and thus maintain adult neurogenesis, are not well defined. Here, we investigate the role of p63, a p53 family member, in adult NPC function in mice. Conditional ablation of p63 in adult NPCs or p63 haploinsufficiency led to reduced numbers of NPCs and newborn neurons in the neurogenic zones of the hippocampus and lateral ventricles and in the olfactory bulb. These reductions were attributable to enhanced apoptosis of NPCs and newborn neurons and were rescued by inhibition of caspase activity, p53, or the p53 apoptotic effector PUMA (p53-upregulated modulator of apoptosis). Moreover, these cellular deficits were functionally important because they led to perturbations in hippocampus-dependent memory formation. These results indicate that p63 regulates the numbers of adult NPCs and adult-born neurons as well as neural stem cell-dependent cognitive functions, and that it does so, at least in part, by inhibiting p53-dependent cell death.",
"title": "p63 Regulates adult neural precursor and newly born neuron survival to control hippocampal-dependent Behavior."
},
{
"docid": "11903247",
"text": "Multiple cellular stressors, including activation of the tumour suppressor p53, can stimulate autophagy. Here we show that deletion, depletion or inhibition of p53 can induce autophagy in human, mouse and nematode cells subjected to knockout, knockdown or pharmacological inhibition of p53. Enhanced autophagy improved the survival of p53-deficient cancer cells under conditions of hypoxia and nutrient depletion, allowing them to maintain high ATP levels. Inhibition of p53 led to autophagy in enucleated cells, and cytoplasmic, not nuclear, p53 was able to repress the enhanced autophagy of p53−/− cells. Many different inducers of autophagy (for example, starvation, rapamycin and toxins affecting the endoplasmic reticulum) stimulated proteasome-mediated degradation of p53 through a pathway relying on the E3 ubiquitin ligase HDM2. Inhibition of p53 degradation prevented the activation of autophagy in several cell lines, in response to several distinct stimuli. These results provide evidence of a key signalling pathway that links autophagy to the cancer-associated dysregulation of p53.",
"title": "Regulation of autophagy by cytoplasmic p53"
},
{
"docid": "4460880",
"text": "Endothelial cells contribute to a subset of cardiac fibroblasts by undergoing endothelial-to-mesenchymal transition, but whether cardiac fibroblasts can adopt an endothelial cell fate and directly contribute to neovascularization after cardiac injury is not known. Here, using genetic fate map techniques, we demonstrate that cardiac fibroblasts rapidly adopt an endothelial-cell-like phenotype after acute ischaemic cardiac injury. Fibroblast-derived endothelial cells exhibit anatomical and functional characteristics of native endothelial cells. We show that the transcription factor p53 regulates such a switch in cardiac fibroblast fate. Loss of p53 in cardiac fibroblasts severely decreases the formation of fibroblast-derived endothelial cells, reduces post-infarct vascular density and worsens cardiac function. Conversely, stimulation of the p53 pathway in cardiac fibroblasts augments mesenchymal-to-endothelial transition, enhances vascularity and improves cardiac function. These observations demonstrate that mesenchymal-to-endothelial transition contributes to neovascularization of the injured heart and represents a potential therapeutic target for enhancing cardiac repair.",
"title": "Mesenchymal-endothelial-transition contributes to cardiac neovascularization"
},
{
"docid": "21521236",
"text": "In a search for mediators of the p53 tumor suppressor pathway, which induces pleiotropic and often antagonistic cellular responses, we identified the long noncoding RNA (lncRNA) NEAT1. NEAT1 is an essential architectural component of paraspeckle nuclear bodies, whose pathophysiological relevance remains unclear. Activation of p53, pharmacologically or by oncogene-induced replication stress, stimulated the formation of paraspeckles in mouse and human cells. Silencing Neat1 expression in mice, which prevents paraspeckle formation, sensitized preneoplastic cells to DNA-damage-induced cell death and impaired skin tumorigenesis. We provide mechanistic evidence that NEAT1 promotes ATR signaling in response to replication stress and is thereby engaged in a negative feedback loop that attenuates oncogene-dependent activation of p53. NEAT1 targeting in established human cancer cell lines induced synthetic lethality with genotoxic chemotherapeutics, including PARP inhibitors, and nongenotoxic activation of p53. This study establishes a key genetic link between NEAT1 paraspeckles, p53 biology and tumorigenesis and identifies NEAT1 as a promising target to enhance sensitivity of cancer cells to both chemotherapy and p53 reactivation therapy.",
"title": "p53 induces formation of NEAT1 lncRNA-containing paraspeckles that modulate replication stress response and chemosensitivity"
},
{
"docid": "10015292",
"text": "Highly regenerative tissues such as blood must possess effective DNA damage responses (DDR) that balance long-term regeneration with protection from leukemogenesis. Hematopoietic stem cells (HSCs) sustain life-long blood production, yet their response to DNA damage remains largely unexplored. We report that human HSCs exhibit delayed DNA double-strand break rejoining, persistent gammaH2AX foci, and enhanced p53- and ASPP1-dependent apoptosis after gamma-radiation compared to progenitors. p53 inactivation or Bcl-2 overexpression reduced radiation-induced apoptosis and preserved in vivo repopulating HSC function. Despite similar protection from irradiation-induced apoptosis, only Bcl-2-overexpressing HSCs showed higher self-renewal capacity, establishing that intact p53 positively regulates self-renewal independently from apoptosis. The reduced self-renewal of HSCs with inactivated p53 was associated with increased spontaneous gammaH2AX foci in secondary transplants of HSCs. Our data reveal distinct physiological roles of p53 that together ensure optimal HSC function: apoptosis regulation and prevention of gammaH2AX foci accumulation upon HSC self-renewal.",
"title": "A distinctive DNA damage response in human hematopoietic stem cells reveals an apoptosis-independent role for p53 in self-renewal."
},
{
"docid": "35684881",
"text": "Tumor-derived p53 mutants can transcriptionally activate a number of promoters of genes involved in cellular proliferation. For this transactivation, mutant p53 does not use the wild-type p53 DNA-binding site, suggesting a mechanism of transactivation that is independent of direct DNA binding. Here we describe our analysis of the domain requirements for mutant p53 to transactivate promoters of the human epidermal growth factor receptor (EGFR), human multiple drug resistance 1 (MDR-1) and human proliferating cell nuclear antigen (PCNA) genes. We also report the identification of a structural domain required for the `gain of function' property of mutant p53-281G. `Gain of function' is measured as the tumorigenicity (in nude mice) of 10(3) murine cells expressing mutant p53 constitutively. We have generated internal deletion mutants of p53-281G deleting conserved domains I, II, III, IV and V, individually. We have also generated one deletion mutant eliminating amino acids 100 through 300 that removes four of the five conserved domains (II–V); another mutant, p53-281G del 393-327, deletes the oligomerization and nonsequence-specific nucleic acid-binding domains of p53. For the EGFR and MDR-1 promoters, all these mutants have significantly lower transactivation ability than intact p53-281G. These deletion mutants, however, significantly activated the pCNA promoter, suggesting that the mechanism of transactivation of the PCNA promoter is different from that of the EGFR and MDR-1 promoters. When expressed constitutively in 10(3) cells, p53-281G del 393-327 was found to be defective in inducing tumor formation in nude mice although intact p53-281G was very efficient. Thus, our results suggest that structural domains near the C-terminus are needed for `gain of function'.",
"title": "`Gain of function' phenotype of tumor-derived mutant p53 requires the oligomerization/nonsequence-specific nucleic acid-binding domain"
},
{
"docid": "9169645",
"text": "The ability of p53 to induce apoptosis requires its sequence-specific DNA binding activity; however, the transactivation-deficient p53(Gln22-Ser23) can still induce apoptosis. Previously, we have shown that the region between residues 23 and 97 in p53 is necessary for such activity. In an effort to more precisely map a domain necessary for apoptosis within the N terminus, we found that deletion of the N-terminal 23 amino acids compromises, but does not abolish, p53 induction of apoptosis. Surprisingly, p53(Delta1-42), which lacks the N-terminal 42 amino acids and the previously defined activation domain, retains the ability to induce apoptosis to an even higher level than wild-type p53. A more extensive deletion, which eliminates the N-terminal 63 amino acids, renders p53 completely inert in mediating apoptosis. In addition, we found that both p53(Delta1-42) and p53(Gln22-Ser23) can activate a subset of cellular p53 targets. Furthermore, we showed that residues 53 and 54 are critical for the apoptotic and transcriptional activities of both p53(Delta1-42) and p53(Gln22-Ser23). Taken together, these data suggest that within residues 43-63 lie an apoptotic domain as well as another transcriptional activation domain. We therefore postulate that the apoptotic activity in p53(Gln22-Ser23) and p53(Delta1-42) is still transcription-dependent.",
"title": "Identification of a novel p53 functional domain that is necessary for mediating apoptosis."
},
{
"docid": "4389394",
"text": "The p53 tumour suppressor is a short-lived protein that is maintained at low levels in normal cells by Mdm2-mediated ubiquitination and subsequent proteolysis. Stabilization of p53 is crucial for its tumour suppressor function. However, the precise mechanism by which ubiquitinated p53 levels are regulated in vivo is not completely understood. By mass spectrometry of affinity-purified p53-associated factors, we have identified herpesvirus-associated ubiquitin-specific protease (HAUSP) as a novel p53-interacting protein. HAUSP strongly stabilizes p53 even in the presence of excess Mdm2, and also induces p53-dependent cell growth repression and apoptosis. Significantly, HAUSP has an intrinsic enzymatic activity that specifically deubiquitinates p53 both in vitro and in vivo. In contrast, expression of a catalytically inactive point mutant of HAUSP in cells increases the levels of p53 ubiquitination and destabilizes p53. These findings reveal an important mechanism by which p53 can be stabilized by direct deubiquitination and also imply that HAUSP might function as a tumour suppressor in vivo through the stabilization of p53.",
"title": "Deubiquitination of p53 by HAUSP is an important pathway for p53 stabilization"
},
{
"docid": "39637840",
"text": "BLM, WRN, and p53 are involved in the homologous DNA recombination pathway. The DNA structure-specific helicases, BLM and WRN, unwind Holliday junctions (HJ), an activity that could suppress inappropriate homologous recombination during DNA replication. Here, we show that purified, recombinant p53 binds to BLM and WRN helicases and attenuates their ability to unwind synthetic HJ in vitro. The p53 248W mutant reduces abilities of both to bind HJ and inhibit helicase activities, whereas the p53 273H mutant loses these abilities. Moreover, full-length p53 and a C-terminal polypeptide (residues 373-383) inhibit the BLM and WRN helicase activities, but phosphorylation at Ser(376) or Ser(378) completely abolishes this inhibition. Following blockage of DNA replication, Ser(15) phospho-p53, BLM, and RAD51 colocalize in nuclear foci at sites likely to contain DNA replication intermediates in cells. Our results are consistent with a novel mechanism for p53-mediated regulation of DNA recombinational repair that involves p53 post-translational modifications and functional protein-protein interactions with BLM and WRN DNA helicases.",
"title": "The processing of Holliday junctions by BLM and WRN helicases is regulated by p53."
},
{
"docid": "25901598",
"text": "Posttranslational modifications mediate important regulatory functions in biology. The acetylation of the p53 transcription factor, for example, promotes transcriptional activation of target genes including p21. Here we show that the acetylation of two lysine residues in p53 promotes recruitment of the TFIID subunit TAF1 to the p21 promoter through its bromodomains. UV irradiation of cells diacetylates p53 at lysines 373 and 382, which in turn recruits TAF1 to a distal p53-binding site on the p21 promoter prior to looping to the core promoter. Disruption of acetyl-p53/bromodomain interaction inhibits TAF1 recruitment to both the distal p53-binding site and the core promoter. Further, the TFIID subunits TAF4, TAF5, and TBP are detected on the core promoter prior to TAF1, suggesting that, upon DNA damage, distinct subunits of TFIID may be recruited separately to the p21 promoter and that the transcriptional activation depends on posttranslational modification of the p53 transcription factor.",
"title": "An acetylation switch in p53 mediates holo-TFIID recruitment."
},
{
"docid": "12240507",
"text": "Diamond-Blackfan anemia (DBA) is a congenital erythroid hypoplasia caused by haploinsufficiency of genes encoding ribosomal proteins (RPs). Perturbed ribosome biogenesis in DBA has been shown to induce a p53-mediated ribosomal stress response. However, the mechanisms of p53 activation and its relevance for the erythroid defect remain elusive. Previous studies have indicated that activation of p53 is caused by the inhibition of mouse double minute 2 (Mdm2), the main negative regulator of p53, by the 5S ribonucleoprotein particle (RNP). Meanwhile, it is not clear whether this mechanism solely mediates the p53-dependent component found in DBA. To approach this question, we crossed our mouse model for RPS19-deficient DBA with Mdm2C305F knock-in mice that have a disrupted 5S RNP–Mdm2 interaction. Upon induction of the Rps19 deficiency, Mdm2C305F reversed the p53 response and improved expansion of hematopoietic progenitors in vitro, and ameliorated the anemia in vivo. Unexpectedly, disruption of the 5S RNP–Mdm2 interaction also led to selective defect in erythropoiesis. Our findings highlight the sensitivity of erythroid progenitor cells to aberrations in p53 homeostasis mediated by the 5S RNP–Mdm2 interaction. Finally, we provide evidence indicating that physiological activation of the 5S RNP-Mdm2-p53 pathway may contribute to functional decline of the hematopoietic system in a cell-autonomous manner over time.",
"title": "Disruption of the 5S RNP–Mdm2 interaction significantly improves the erythroid defect in a mouse model for Diamond-Blackfan anemia"
},
{
"docid": "27949347",
"text": "TP53 is the most frequently mutated gene in human cancer. Functionally, p53 is activated by a host of stress stimuli and, in turn, governs an exquisitely complex anti-proliferative transcriptional program that touches upon a bewildering array of biological responses. Despite the many unveiled facets of the p53 network, a clear appreciation of how and in what contexts p53 exerts its diverse effects remains unclear. How can we interpret p53's disparate activities and the consequences of its dysfunction to understand how cell type, mutation profile, and epigenetic cell state dictate outcomes, and how might we restore its tumor-suppressive activities in cancer?",
"title": "Putting p53 in Context"
},
{
"docid": "6896063",
"text": "p53 functions as a transcription factor involved in cell-cycle control, DNA repair, apoptosis and cellular stress responses. However, besides inducing cell growth arrest and apoptosis, p53 activation also modulates cellular senescence and organismal aging. Senescence is an irreversible cell-cycle arrest that has a crucial role both in aging and as a robust physiological antitumor response, which counteracts oncogenic insults. Therefore, via the regulation of senescence, p53 contributes to tumor growth suppression, in a manner strictly dependent by its expression and cellular context. In this review, we focus on the recent advances on the contribution of p53 to cellular senescence and its implication for cancer therapy, and we will discuss p53’s impact on animal lifespan. Moreover, we describe p53-mediated regulation of several physiological pathways that could mediate its role in both senescence and aging.",
"title": "Senescence and aging: the critical roles of p53"
},
{
"docid": "29367554",
"text": "BACKGROUND & AIMS Although the p53 tumor suppressor has been extensively studied, many critical questions remain unanswered about the biological functions of p53 homologs, p73 and p63. Accumulating evidence suggests that both p73 and p63 play important roles in regulation of apoptosis, cell differentiation, and therapeutic drug sensitivity. METHODS Gastric epithelial cells were cocultured with Helicobacter pylori, and the roles of p63 and p73 proteins were assessed by luciferase reporter, real-time polymerase chain reaction, immunoblotting, and cell survival assays. Short hairpin RNA and dominant-negative mutants were used to inhibit activity of p73 and p63 isoforms. Human and murine gastric tissues were analyzed by immunohistochemistry with p73 and p63 antibodies and modified Steiner's silver method. RESULTS Interaction of H pylori with gastric epithelial cells leads to robust up-regulation of p73 protein in vitro and in vivo in human gastritis specimens and H pylori-infected mice. The p73 increase resulted in up-regulation of pro-apoptotic genes, NOXA, PUMA, and FAS receptor in gastric epithelial cells. Down-regulation of p73 activity suppressed cell death and Fas receptor induced by H pylori. Bacterial virulence factors within the cag pathogenicity island, c-Abl tyrosine kinase, and interaction with p63 isoforms control the activity of p73. CONCLUSION Our findings implicate p73 in H pylori-induced apoptosis and more generally suggest that the p53 family may play a role in the epithelial cell response to H pylori infection.",
"title": "Interaction of Helicobacter pylori with gastric epithelial cells is mediated by the p53 protein family."
},
{
"docid": "28107602",
"text": "The oncogene MDMX is overexpressed in many cancers, leading to suppression of the tumor suppressor p53. Inhibitors of the oncogene product MDMX therefore might help reactivate p53 and enhance the efficacy of DNA-damaging drugs. However, we currently lack a quantitative understanding of how MDMX inhibition affects the p53 signaling pathway and cell sensitivity to DNA damage. Live cell imaging showed that MDMX depletion triggered two distinct phases of p53 accumulation in single cells: an initial postmitotic pulse, followed by low-amplitude oscillations. The response to DNA damage was sharply different in these two phases; in the first phase, MDMX depletion was synergistic with DNA damage in causing cell death, whereas in the second phase, depletion of MDMX inhibited cell death. Thus a quantitative understanding of signal dynamics and cellular states is important for designing an optimal schedule of dual-drug administration.",
"title": "Schedule-dependent interaction between anticancer treatments"
},
{
"docid": "43880096",
"text": "Activation of p53 can occur in response to a number of cellular stresses, including DNA damage, hypoxia and nucleotide deprivation. Several forms of DNA damage have been shown to activate p53, including those generated by ionising radiation (IR), radio-mimetic drugs, ultraviolet light (UV) and chemicals such as methyl methane sulfonate (MMS). Under normal conditions, p53 levels are maintained at a low state by virtue of the extremely short-half life of the polypeptide. In addition to this, p53 normally exists in an largely inactive state that is relatively inefficient at binding to DNA and activating transcription. Activation of p53 in response to DNA damage is associated with a rapid increase in its levels and with an increased ability of p53 to bind DNA and mediate transcriptional activation. This then leads to the activation of a number of genes whose products trigger cell-cycle arrest, apoptosis, or DNA repair. Recent work has suggested that this regulation is brought about largely through DNA damage triggering a series of phosphorylation, de-phosphorylation and acetylation events on the p53 polypeptide. Here, we discuss the nature of these modifications, the enzymes that bring them about, and how changes in p53 modification lead to p53 activation.",
"title": "Regulation of p53 in response to DNA damage"
},
{
"docid": "42489926",
"text": "p53 regulates a key pathway which protects normal tissues from tumor development that may result from diverse forms of stress. In the absence of stress, growth suppressive and proapoptotic activity of p53 is inhibited by MDM2 which binds p53 and negatively regulates its activity and stability. MDM2 antagonists could activate p53 and may offer a novel therapeutic approach to cancer. Recently, we identified the first potent and selective low molecular weight inhibitors of MDM2-p53 binding, the Nutlins. These molecules activate the p53 pathway and suppress tumor growth in vitro and in vivo. They represent valuable new tools for studying the p53 pathway and its defects in cancer. Nutlins induce p53-dependent apoptosis in human cancer cells but appear cytostatic to proliferating normal cells. Their potent activity against osteosarcoma xenografts suggests that MDM2 antagonists may have clinical utility in the treatment of tumors with wild-type p53.",
"title": "Small-molecule antagonists of p53-MDM2 binding: research tools and potential therapeutics."
},
{
"docid": "34103335",
"text": "A long-standing hypothesis on tumorigenesis is that cell division failure, generating genetically unstable tetraploid cells, facilitates the development of aneuploid malignancies. Here we test this idea by transiently blocking cytokinesis in p53-null (p53-/-) mouse mammary epithelial cells (MMECs), enabling the isolation of diploid and tetraploid cultures. The tetraploid cells had an increase in the frequency of whole-chromosome mis-segregation and chromosomal rearrangements. Only the tetraploid cells were transformed in vitro after exposure to a carcinogen. Furthermore, in the absence of carcinogen, only the tetraploid cells gave rise to malignant mammary epithelial cancers when transplanted subcutaneously into nude mice. These tumours all contained numerous non-reciprocal translocations and an 8–30-fold amplification of a chromosomal region containing a cluster of matrix metalloproteinase (MMP) genes. MMP overexpression is linked to mammary tumours in humans and animal models. Thus, tetraploidy enhances the frequency of chromosomal alterations and promotes tumour development in p53-/- MMECs.",
"title": "Cytokinesis failure generating tetraploids promotes tumorigenesis in p53-null cells"
},
{
"docid": "47018050",
"text": "Here, we report that genome editing by CRISPR–Cas9 induces a p53-mediated DNA damage response and cell cycle arrest in immortalized human retinal pigment epithelial cells, leading to a selection against cells with a functional p53 pathway. Inhibition of p53 prevents the damage response and increases the rate of homologous recombination from a donor template. These results suggest that p53 inhibition may improve the efficiency of genome editing of untransformed cells and that p53 function should be monitored when developing cell-based therapies utilizing CRISPR–Cas9. CRISPR–Cas9-induced DNA damage triggers p53 to limit the efficiency of gene editing in immortalized human retinal pigment epithelial cells.",
"title": "CRISPR–Cas9 genome editing induces a p53-mediated DNA damage response"
},
{
"docid": "25682129",
"text": "The sequence-specific binding to DNA is crucial for the p53 tumor suppressor function. To investigate the constraints imposed on p53-DNA recognition by nucleosomal organization, we studied binding of the p53 DNA binding domain (p53DBD) and full-length wild-type p53 protein to a single p53 response element (p53RE) placed near the nucleosomal dyad in six rotational settings. We demonstrate that the strongest p53 binding occurs when the p53RE in the nucleosome is bent in the same direction as observed for the p53-DNA complexes in solution and in co-crystals. The p53RE becomes inaccessible, however, if its orientation in the core particle is changed by approximately 180 degrees. Our observations indicate that the orientation of the binding sites on a nucleosome may play a significant role in the initial p53-DNA recognition and subsequent cofactor recruitment.",
"title": "p53 binding to nucleosomal DNA depends on the rotational positioning of DNA response element."
},
{
"docid": "21295300",
"text": "The phosphatidylinositol-3-kinase-like kinase ATM (ataxia-telangiectasia mutated) has a central role in coordinating DNA damage responses, including cell-cycle checkpoint control, DNA repair and apoptosis. Mutations of ATM cause a spectrum of defects ranging from neurodegeneration to cancer predisposition. However, the mechanism by which DNA damage activates ATM is poorly understood. Here we show that Cdk5 (cyclin-dependent kinase 5), activated by DNA damage, directly phosphorylates ATM at Ser 794 in post-mitotic neurons. Phosphorylation at Ser 794 precedes, and is required for, ATM autophosphorylation at Ser 1981, and activates ATM kinase activity. The Cdk5-ATM signal regulates phosphorylation and function of the ATM targets p53 and H2AX. Interruption of the Cdk5-ATM pathway attenuates DNA-damage-induced neuronal cell cycle re-entry and expression of the p53 targets PUMA and Bax, protecting neurons from death. Thus, activation of Cdk5 by DNA damage serves as a critical signal to initiate the ATM response and regulate ATM-dependent cellular processes.",
"title": "Phosphorylation of ATM by Cdk5 mediates DNA damage signaling and regulates neuronal death"
},
{
"docid": "5468807",
"text": "ARID1A, encoding a subunit of the SWI/SNF chromatin-remodelling complex, is the most frequently mutated epigenetic regulator across all human cancers. ARID1A and TP53 mutations are typically mutually exclusive. Therapeutic approaches that correlate with this genetic characteristic remain to be explored. Here, we show that HDAC6 activity is essential in ARID1A-mutated ovarian cancers. Inhibition of HDAC6 activity using a clinically applicable small-molecule inhibitor significantly improved the survival of mice bearing ARID1A-mutated tumours. This correlated with the suppression of growth and dissemination of ARID1A-mutated, but not wild-type, tumours. The dependence on HDAC6 activity in ARID1A-mutated cells correlated with a direct transcriptional repression of HDAC6 by ARID1A. HDAC6 inhibition selectively promoted apoptosis of ARID1A-mutated cells. HDAC6 directly deacetylates Lys120 of p53, a pro-apoptotic post-translational modification. Thus, ARID1A mutation inactivates the apoptosis-promoting function of p53 by upregulating HDAC6. Together, these results indicate that pharmacological inhibition of HDAC6 is a therapeutic strategy for ARID1A-mutated cancers.",
"title": "ARID1A-mutated ovarian cancers depend on HDAC6 activity"
},
{
"docid": "21557055",
"text": "The tumor suppressor protein, p53, plays a critical role in mediating cellular response to stress signals by regulating genes involved in cell cycle arrest and apoptosis. p53 is believed to be inactive for DNA binding unless its C terminus is modified or structurally altered. We show that unmodified p53 actively binds to two sites at -1.4 and -2.3 kb within the chromatin-assembled p21 promoter and requires the C terminus and the histone acetyltransferase, p300, for transcription. Acetylation of the C terminus by p300 is not necessary for binding or promoter activation. Instead, p300 acetylates p53-bound nucleosomes in the p21 promoter with spreading to the TATA box. Thus, p53 is an active DNA and chromatin binding protein that may selectively regulate its target genes by recruitment of specific cofactors to structurally distinct binding sites.",
"title": "Transcriptional regulation by p53 through intrinsic DNA/chromatin binding and site-directed cofactor recruitment."
},
{
"docid": "9483851",
"text": "p53 is a crucial tumour suppressor that responds to diverse stress signals by orchestrating specific cellular responses, including transient cell cycle arrest, cellular senescence and apoptosis, which are all processes associated with tumour suppression. However, recent studies have challenged the relative importance of these canonical cellular responses for p53-mediated tumour suppression and have highlighted roles for p53 in modulating other cellular processes, including metabolism, stem cell maintenance, invasion and metastasis, as well as communication within the tumour microenvironment. In this Opinion article, we discuss the roles of classical p53 functions, as well as emerging p53-regulated processes, in tumour suppression.",
"title": "Unravelling mechanisms of p53-mediated tumour suppression"
},
{
"docid": "26059876",
"text": "Ku70, a known nonhomologous end-joining (NHEJ) factor, also functions in tumor suppression, although this molecular mechanism remains uncharacterized. Previously, we showed that mice deficient for DNA ligase IV (Lig4), another key NHEJ factor, succumbed to aggressive lymphoma in the absence of tumor suppressor p53. However, the tumor phenotype is abrogated by the introduction of a hypomorphic mutant p53R172P, which impaired p53-mediated apoptosis but not cell-cycle arrest. However, Lig4−/−p53R172P mice succumbed to severe diabetes. To further elucidate the role of NHEJ and p53-mediated apoptosis in vivo, we bred Ku70−/− p53R172P mice. Unexpectedly, these mice were free of diabetes, although 80% of the mutant mice had abnormally enlarged colons with pronounced inflammation. Remarkably, most of these mutant mice progressed to dysplasia, adenoma and adenocarcinoma; this is in contrast to the Lig4−/−p53R172P phenotype, strongly suggesting an NHEJ-independent function of Ku70. Significantly, our analyses of Ku70−/−p53R172P colonic epithelial cells show nuclear stabilization of β-catenin accompanied by higher expression of cyclin D1 and c-Myc in affected colon sections than in control samples. This is not due to the p53 mutation, as Ku70−/− mice share this phenotype. Our results not only unravel a novel function of Ku70 essential for colon homeostasis, but also establish an excellent in vivo model in which to study how chronic inflammation and abnormal cellular proliferation underlie tumorigenesis and tumor progression in the colon.",
"title": "A novel Ku70 function in colorectal homeostasis separate from nonhomologous end joining"
},
{
"docid": "7465900",
"text": "BACKGROUND & AIMS Helicobacter pylori-induced gastric epithelial cell (GEC) apoptosis is a complex process that includes activation of the tumor suppressor p53. p53-mediated apoptosis involves p53 activation, bax transcription, and cytochrome c release from mitochondria. Apurinic/apyrimidinic endonuclease-1 (APE-1) regulates transcriptional activity of p53, and H pylori induce APE-1 expression in human GECs. H pylori infection increases intracellular calcium ion concentration [Ca2+]i of GECs, which induces APE-1 acetylation. We investigated the effects of H pylori infection and APE-1 acetylation on GEC apoptosis. METHODS AGS cells (wild-type or with suppressed APE-1), KATO III cells, and cells isolated from gastric biopsy specimens were infected with H pylori. Effects were examined by immunoblotting, real-time reverse-transcription polymerase chain reaction, immunoprecipitation, immunofluorescence microscopy, chromatin immunoprecipitation, mobility shift, DNA binding, and luciferase assays. RESULTS H pylori infection increased [Ca2+]i and acetylation of APE-1 in GECs, but the acetylation status of APE-1 did not affect the transcriptional activity of p53. In GECs, expression of a form of APE-1 that could not be acetylated increased total and mitochondrial levels of Bax and induced release of cytochrome c and fragmentation of DNA; expression of wild-type APE-1 reduced these apoptotic events. We identified a negative calcium response element in the human bax promoter and found that poly (adenosine diphosphate-ribose) polymerase 1 recruited the acetylated APE-1/histone deacetylase-1 repressor complex to bax nCaRE. CONCLUSIONS H pylori-mediated acetylation of APE-1 suppresses Bax expression; this prevents p53-mediated apoptosis when H pylori infect GECs.",
"title": "Acetylation of apurinic/apyrimidinic endonuclease-1 regulates Helicobacter pylori-mediated gastric epithelial cell apoptosis."
}
] |
5497
|
What kinds of exchange-traded funds (ETFs) should specifically be avoided?
|
[
{
"docid": "210257",
"text": "\"As with ANY investment the first answer is....do not invest in any that you do not fully understand. ETF's are very versatile and can be used for many different people for many different parts of their portfolio, so I don't think there can be a blanket statement of \"\"this\"\" one is good or bad for all.\"",
"title": ""
},
{
"docid": "86627",
"text": "\"Stay away from leveraged or synthetic ETFs. This answer talks about why leveraged ETFs are dangerous. There are numerous articles to be found by searching for \"\"leveraged etf\"\". My answer to this question links to one of the more accessible explanations I've read.\"",
"title": ""
},
{
"docid": "324697",
"text": "One of the key things to look for is trading volume. I think the price spread will be better on high volume ETFs, which means you'll be able to sell for more when the time comes. Check Google or Yahoo finance for those stats.",
"title": ""
}
] |
[
{
"docid": "332924",
"text": "\"I recommend avoiding trading directly in commodities futures and options. If you're not prepared to learn a lot about how futures markets and trading works, it will be an experience fraught with pitfalls and lost money – and I am speaking from experience. Looking at stock-exchange listed products is a reasonable approach for an individual investor desiring added diversification for their portfolio. Still, exercise caution and know what you're buying. It's easy to access many commodity-based exchange-traded funds (ETFs) on North American stock exchanges. If you already have low-cost access to U.S. markets, consider this option – but be mindful of currency conversion costs, etc. Yet, there is also a European-based company, ETF Securities, headquartered in Jersey, Channel Islands, which offers many exchange-traded funds on European exchanges such as London and Frankfurt. ETF Securities started in 2003 by first offering a gold commodity exchange-traded fund. I also found the following: London Stock Exchange: Frequently Asked Questions about ETCs. The LSE ETC FAQ specifically mentions \"\"ETF Securities\"\" by name, and addresses questions such as how/where they are regulated, what happens to investments if \"\"ETF Securities\"\" were to go bankrupt, etc. I hope this helps, but please, do your own due diligence.\"",
"title": ""
},
{
"docid": "161201",
"text": "Your assumption that funds sold in GBP trade in GBP is incorrect. In general funds purchase their constituent stocks in the fund currency which may be different to the subscription currency. Where the subscription currency is different from the fund currency subscriptions are converted into the fund currency before the extra money is used to increase holdings. An ETF, on the other hand, does not take subscriptions directly but by creation (and redemption) of shares. The principle is the same however; monies received from creation of ETF shares are converted into the fund currency and then used to buy stock. This ensures that only one currency transaction is done. In your specific example the fund currency will be USD so your purchase of the shares (assuming there are no sellers and creation occurs) will be converted from GBP to USD and held in that currency in the fund. The fund then trades entirely in USD to avoid currency risk. When you want to sell your exposure (supposing redemption occurs) enough holdings required to redeem your money are sold to get cash in USD and then converted to GBP before paying you. This means that trading activity where there is no need to convert to GBP (or any other currency) does not incur currency conversion costs. In practice funds will always have some cash (or cash equivalents) on hand to pay out redemptions and will have an idea of the number and size of redemptions each calendar period so will use futures and swaps to mitigate FX risk. Where the same firm has two funds traded in different currencies with the same objectives it is likely that one is a wrapper for the other such that one simply converts the currency and buys the other currency denominated ETF. As these are exchange traded funds with a price in GBP the amount you pay for the ETF or gain on selling it is the price given and you will not have to consider currency exchange as that should be done internally as explained above. However, there can be a (temporary) arbitrage opportunity if the price in GBP does not reflect the price in USD and the exchange rate put together.",
"title": ""
},
{
"docid": "311192",
"text": "\"Bit hesitant to put this in an answer as I don't know if specific investment advice is appropriate, but this has grown way too long for a comment. The typical answer given for people who don't have the time, experience, knowledge or inclination to pick specific stocks to hold should instead invest in ETFs (exchange-traded index funds.) What these basically do is attempt to simulate a particular market or stock exchange. An S&P 500 index fund will (generally) attempt to hold shares in the stocks that make up that index. They only have to follow an index, not try to beat it so are called \"\"passively\"\" managed. They have very low expense ratios (far below 1%) and are considered a good choice for investors who want to hold stock without significant effort or expense and who's main goal is time in the market. It's a contentious topic but on average an index (and therefore an index fund) will go even with or outperform most actively managed funds. With a sufficiently long investment horizon, which you have, these may be ideal for you. Trading in ETFs is also typically cheap because they are traded like stock. There are plenty of low-fee online brokers and virtually all will allow trading in ETFs. My broker even has a list of several hundred popular ETFs that can be traded for free. The golden rule in investing is that you should never buy into something you don't understand. Don't buy individual stock with little information: it's often little more than gambling. The same goes for trading platforms like Loyal3. Don't use them unless you know their business model and what they stand to gain from your custom. As mentioned I can trade certain funds for free with my broker, but I know why they can offer that and how they're still making money.\"",
"title": ""
},
{
"docid": "29184",
"text": "\"Does the bolded sentence apply for ETFs and ETF companies? No, the value of an ETF is determined by an exchange and thus the value of the share is whatever the trading price is. Thus, the price of an ETF may go up or down just like other securities. Money market funds can be a bit different as the mutual fund company will typically step in to avoid \"\"Breaking the Buck\"\" that could happen as a failure for that kind of fund. To wit, must ETF companies invest a dollar in the ETF for every dollar that an investor deposited in this aforesaid ETF? No, because an ETF is traded as shares on the market, unless you are using the creation/redemption mechanism for the ETF, you are buying and selling shares like most retail investors I'd suspect. If you are using the creation/redemption system then there are baskets of other securities that are being swapped either for shares in the ETF or from shares in the ETF.\"",
"title": ""
},
{
"docid": "9672",
"text": "\"You're talking about money in a savings account, and avoiding the risks posed by an ongoing crisis, and avoiding risk. If you are risk-averse, and likely to need your money in the short term, you should not put your money in the stock market, even in \"\"safe\"\" stocks like P&G/Coca-Cola/etc. Even these safe stocks are at risk of wild price swings in the short- to intermediate-term, especially in the event of international crises such as major European debt defaults and the like. These stocks are suitable for long-term growth objectives, but they are not as a replacement for a savings account. Coca-Cola lost a third of its value between 2007 and 2009. (It's recovered, and is currently doing better than ever.) P&G went from $74/share to $46/share. (It's partially recovered and back at $63). On the other hand, these stocks may indeed be suitable as long-term investments to protect you against local currency inflation. And yes, they even pay dividends. If you're after this investment, a good option is probably a sector-specific exchange-traded fund, such as a consumer-staples ETF. It will likely be more diversified and safer than anything you could come up with using a list of individual stocks. You can also investigate recommendations that show up when you search for a \"\"defensive ETF\"\". If you do not wish to buy the ETF directly, you can also look at listings of the ETF's holdings. Read the prospectus for an idea of the risks associated with these funds. You can buy these funds with any brokerage that gives you access to US stock exchanges.\"",
"title": ""
},
{
"docid": "119819",
"text": "\"You seem to be assuming that ETFs must all work like the more traditional closed-end funds, where the market price per share tends—based on supply and demand—to significantly deviate from the underlying net asset value per share. The assumption is simplistic. What are traditionally referred to as closed-end funds (CEFs), where unit creation and redemption are very tightly controlled, have been around for a long time, and yes, they do often trade at a premium or discount to NAV because the quantity is inflexible. Yet, what is generally meant when the label \"\"ETF\"\" is used (despite CEFs also being both \"\"exchange-traded\"\" and \"\"funds\"\") are those securities which are not just exchange-traded, and funds, but also typically have two specific characteristics: (a) that they are based on some published index, and (b) that a mechanism exists for shares to be created or redeemed by large market participants. These characteristics facilitate efficient pricing through arbitrage. Essentially, when large market participants notice the price of an ETF diverging from the value of the shares held by the fund, new units of the ETF can get created or redeemed in bulk. The divergence quickly narrows as these participants buy or sell ETF units to capture the difference. So, the persistent premium (sometimes dear) or discount (sometimes deep) one can easily witness in the CEF universe tend not to occur with the typical ETF. Much of the time, prices for ETFs will tend to be very close to their net asset value. However, it isn't always the case, so proceed with some caution anyway. Both CEF and ETF providers generally publish information about their funds online. You will want to find out what is the underlying Net Asset Value (NAV) per share, and then you can determine if the market price trades at a premium or a discount to NAV. Assuming little difference in an ETF's price vs. its NAV, the more interesting question to ask about an ETF then becomes whether the NAV itself is a bargain, or not. That means you'll need to be more concerned with what stocks are in the index the fund tracks, and whether those stocks are a bargain, or not, at their current prices. i.e. The ETF is a basket, so look at each thing in the basket. Of course, most people buy ETFs because they don't want to do this kind of analysis and are happy with market average returns. Even so, sector-based ETFs are often used by traders to buy (or sell) entire sectors that may be undervalued (or overvalued).\"",
"title": ""
},
{
"docid": "130188",
"text": "ETFs trade on specific exchanges. If your broker deals with those exchanges, you should have access to the ETF. If your broker does not deal with that exchange, then you will not have access through that broker. This is different than, say, mutual funds, which don't trade on the exchanges are proprietary to certain brokerages or financial institutions.",
"title": ""
},
{
"docid": "489103",
"text": "\"Ask your trading site for their definition of \"\"ETF\"\". The term itself is overloaded/ambiguous. Consider: If \"\"ETF\"\" is interpreted liberally, then any fund that trades on a [stock] exchange is an exchange-traded fund. i.e. the most literal meaning implied by the acronym itself. Whereas, if \"\"ETF\"\" is interpreted more narrowly and in the sense that most market participants might use it, then \"\"ETF\"\" refers to those exchange-traded funds that specifically have a mechanism in place to ensure the fund's current price remains close to its net asset value. This is not the case with closed-end funds (CEFs), which often trade at either a premium or a discount to their underlying net asset value.\"",
"title": ""
},
{
"docid": "304023",
"text": "\"ETF Creation and Redemption Process notes the process: While ETF trading occurs on an exchange like stocks, the process by which their shares are created is significantly different. Unless a company decides to issue more shares, the supply of shares of an individual stock trading in the marketplace is finite. When demand increases for shares of an ETF, however, Authorized Participants (APs) have the ability to create additional shares on demand. Through an \"\"in kind\"\" transfer mechanism, APs create ETF units in the primary market by delivering a basket of securities to the fund equal to the current holdings of the ETF. In return, they receive a large block of ETF shares (typically 50,000), which are then available for trading in the secondary market. This ETF creation and redemption process helps keep ETF supply and demand in continual balance and provides a \"\"hidden\"\" layer of liquidity not evident by looking at trading volumes alone. This process also works in reverse. If an investor wants to sell a large block of shares of an ETF, even if there seems to be limited liquidity in the secondary market, APs can readily redeem a block of ETF shares by gathering enough shares of the ETF to form a creation unit and then exchanging the creation unit for the underlying securities. Thus, the in-kind swap to the underlying securities is only done by APs so the outflow would be these individuals taking a large block of the ETF and swapping it for the underlying securities. The APs would be taking advantage of the difference between what the ETF's trading value and the value of the underlying securities.\"",
"title": ""
},
{
"docid": "129070",
"text": "You could use a stock-only ISA and invest in Exchange Traded Funds (ETFs). ETFs are managed mutual funds that trade on open exchanges in the same manner as stocks. This changes the specific fund options you have open to you, but there are so many ETFs at this point that any sector you want to invest in is almost certainly represented.",
"title": ""
},
{
"docid": "402046",
"text": "Ending up with nothing is an unlikely situation unless you invest 100% in a company stock and the company goes under. In order to give you a good answer we need to see what options your employer gives for 401k investments. The best advice would be to take a list of all options that your employer allows and talk with a financial advisor. Here are a few options that you may or may not have as an option from an employer: Definitions from wikipedia: A target-date fund – also known as a lifecycle, dynamic-risk or age-based fund – is a collective investment scheme, usually a mutual fund, designed to provide a simple investment solution through a portfolio whose asset allocation mix becomes more conservative as the target date (usually retirement) approaches. An index fund or index tracker is a collective investment scheme (usually a mutual fund or exchange-traded fund) that aims to replicate the movements of an index of a specific financial market... An exchange-traded fund (ETF) is an investment fund traded on stock exchanges, much like stocks.[1] An ETF holds assets such as stocks, commodities, or bonds, and trades close to its net asset value over the course of the trading day. Most ETFs track an index, such as a stock index or bond index. ETFs may be attractive as investments because of their low costs, tax efficiency, and stock-like features. The capital stock (or stock) of an incorporated business constitutes the equity stake of its owners. Which one can you lose everything in? You can lose everything in stocks by the company going under. In Index funds the entire market that it follows would have to collapse. The chances are slim here since the index made up of several companies. The S&P 500 is made up of 500 leading companies publicly traded in the U.S. A Pacific-Europe index such as MSCI EAFE Index is made up of 907 companies. The chances of losing everything in an ETF are also slim. The ETF that follows the S&P 500 is made up of 500 companies. An Pacific-Europe ETF such as MSCI EAFE ETF is made up of 871 companies. Target date funds are also slim to lose everything. Target date funds are made up of several companies like indexes and etfs and also mix in bonds and other investments depending on your age. What would I recommend? I would recommend the Index funds and/or ETFs that have the lowest fee that make up the following strategy for your age: Why Not Target Date Funds or Stocks? Target date funds have high fees. Later in life when you are closer to retirement you may want to add bonds to your portfolio. At that time if this is the only option to add bonds then you can change your elections. Stocks are too risky for you with your current knowledge. If your company matches by buying their stock you may want to consider reallocating that stock at certain points to your Index funds or ETFs.",
"title": ""
},
{
"docid": "120059",
"text": "\"Generally, ETFs work on the basis that there exists a pair of values that can be taken at any moment in time: A Net Asset Value of each share in the fund and a trading market price of each share in the fund. It may help to picture these in baskets of about 50,000 shares for the creation/redemption process. If the NAV is greater than the market price, then arbitrageurs will buy up shares at the market price and do an \"\"in-kind\"\" transaction that will be worth the NAV value that the arbitrageurs could turn around and sell for an immediate profit. If the market price is greater than the NAV, then the arbitrageurs will buy up the underlying securities that can be exchanged \"\"in-kind\"\" for shares in the fund that can then be sold on the market for an immediate profit. What is the ETF Creation/Redemption Mechanism? would be a source on this though I imagine there are others. Now, in the case of VXX, there is something to be said for how much trading is being done and what impact this can have. From a July 8, 2013 Yahoo Finance article: At big option trade in the iPath S&P 500 VIX Short-Term Futures Note is looking for another jump in volatility. More than 250,000 VXX options have already traded, twice its daily average over the last month. optionMONSTER systems show that a trader bought 13,298 August 26 calls for the ask price of $0.24 in volume that was 6 times the strike's previous open interest, clearly indicating new activity. Now the total returns of the ETF are a combination of changes in share price plus what happens with the distributions which could be held as cash or reinvested to purchase more shares.\"",
"title": ""
},
{
"docid": "349668",
"text": "This is more than likely a thing about your financial institution and the exchanges where they trade shares. Some exchanges cannot/will not handle odd lot transactions. Most established brokerages have software and accounting systems that will deal in round lots with the exchanges, but can track your shares individually. Sometimes specific stocks cannot be purchased in odd lots due to circumstances specific to that stock (trading only on a specific exchange, for example). Most brokerages offer dollar-cost averaging programs, but may limit which stocks are eligible, due to odd lot and partial share purchases. Check with your brokerage to see if they can support odd lot and/or DCA purchases. You may find another similar ETF with similar holdings that has better trading conditions, or might consider an open-end mutual fund with similar objectives. Mutual funds allow partial share purchases (you have $100 to invest today, and they issue you 35.2 shares, for example).",
"title": ""
},
{
"docid": "472663",
"text": "\"An Exchange-Traded Fund (ETF) is a special type of mutual fund that is traded on the stock exchange like a stock. To invest, you buy it through a stock broker, just as you would if you were buying an individual stock. When looking at a mutual fund based in the U.S., the easiest way to tell whether or not it is an ETF is by looking at the ticker symbol. Traditional mutual funds have ticker symbols that end in \"\"X\"\", and ETFs have ticker symbols that do not end in \"\"X\"\". The JPMorgan Emerging Markets Equity Fund, with ticker symbol JFAMX, is a traditional mutual fund, not an ETF. JPMorgan does have ETFs; the JPMorgan Diversified Return Emerging Markets Equity ETF, with ticker symbol JPEM, is an example. This ETF invests in similar stocks as JFAMX; however, because it is an index-based fund instead of an actively managed fund, it has lower fees. If you aren't sure about the ticker symbol, the advertising/prospectus of any ETF should clearly state that it is an ETF. (In the example of JPEM above, they put \"\"ETF\"\" right in the fund name.) If you don't see ETF mentioned, it is most likely a traditional mutual fund. Another way to tell is by looking at the \"\"investment minimums\"\" of the fund. JFAMX has a minimum initial investment of $1000. ETFs, however, do not have an investment minimum listed; because it is traded like a stock, you simply buy whole shares at whatever the current share price is. So if you look at the \"\"Fees and Investment Minimums\"\" section of the JPEM page, you'll see the fees listed, but not any investment minimums.\"",
"title": ""
},
{
"docid": "367960",
"text": "\"I think you are asking about actively managed funds vs. indexes and possibly also vs. diversified funds like target date funds. This is also related to the question of mutual fund vs. ETF. First, a fund can be either actively managed or it can attempt to track an index. An actively managed fund has a fund manager who tries to find the best stocks to invest in within some constraints, like \"\"this fund invests in large cap US companies\"\". An index fund tries to match as closely as possible the performance of an index like the S&P 500. A fund may also try to offer a portfolio that is suitable for someone to put their entire account into. For example, a target date fund is a fund that may invest in a mix of stocks, bonds and foreign stock in a proportion that would be appropriate to someone expecting to retire in a certain year. These are not what people tend to think of as the canonical examples of mutual funds, even though they share the same legal structure and investment mechanisms. Secondly, a fund can either be a traditional mutual fund or it can be an exchange traded fund (ETF). To invest in a traditional mutual fund, you send money to the fund, and they give you a number of shares equal to what that money would have bought of the net asset value (NAV) of the fund at the end of trading on the day they receive your deposit, possibly minus a sales charge. To invest in an ETF, you buy shares of the ETF on the stock market like any other stock. Under the covers, an ETF does have something similar to the mechanism of depositing money to get shares, but only big traders can use that, and it's not used for investing, but only for people who are making a market in the stock (if lots of people are buying VTI, Big Dealer Co will get 100,000 shares from Vanguard so that they can sell them on the market the next day). Historically and traditionally, ETFs are associated with an indexing strategy, while if not specifically mentioned, people assume that traditional mutual funds are actively managed. Many ETFs, notably all the Vanguard ETFs, are actually just a different way to hold the same underlying fund. The best way to understand this is to read the prospectus for a mutual fund and an ETF. It's all there in reasonably plain English.\"",
"title": ""
},
{
"docid": "531180",
"text": "You can look into specific market targeted mutual funds or ETF's. For Norway, for example, look at NORW. If you want to purchase specific stocks, then you'd better be ready to trade on local stock exchanges in local currency. ETrade allows trading on some of the international stock exchanges (in Asia they have Hong Kong and Japan, in Europe they have the UK, Germany and France, and in the Americas they have the US and Canada). Some of the companies you're interested in might be trading there.",
"title": ""
},
{
"docid": "39265",
"text": "In addition to the higher risk as pointed out by @JamesRoth, you also need to consider that there are regulations against 'naked shorting' so you generally need to either own the security, or have someone that is willing to 'loan' the security to you in order to sell short. If you own a stock you are shorting, the IRS could view the transaction as a Sell followed by a buy taking place in a less than 30 day period and you could be subject to wash-sale rules. This added complexity (most often the finding of someone to loan you the security you are shorting) is another reason such trades are considered more advanced. You should also be aware that there are currently a number of proposals to re-instate the 'uptick rule' or some circuit-breaker variant. Designed to prevent short-sellers from driving down the price of a stock (and conducting 'bear raids etc) the first requires that a stock trade at the same or higher price as prior trades before you can submit a short. In the latter shorting would be prohibited after a stock price had fallen a given percentage in a given amount of time. In either case, should such a rule be (re)established then you could face limitations attempting to execute a short which you would not need to worry about doing simple buys or sells. As to vehicles that would do this kind of thing (if you are convinced we are in a bear market and willing to take the risk) there are a number of ETF's classified as 'Inverse Exchange Traded Funds (ETF's) for a variety of markets that via various means seek to deliver a return similar to that of 'shorting the market' in question. One such example for a common broad market is ticker SH the ProShares Short S&P500 ETF, which seeks to deliver a return that is the inverse of the S&P500 (and as would be predicted based on the roughly +15% performance of the S&P500 over the last 12 months, SH is down roughly -15% over the same period). The Wikipedia article on inverse ETF's lists a number of other such funds covering various markets. I think it should be noted that using such a vehicle is a pretty 'aggressive bet' to take in reaction to the belief that a bear market is imminent. A more conservative approach would be to simply take money out of the market and place it in something like CD's or Treasury instruments. In that case, you preserve your capital, regardless of what happens in the market. Using an inverse ETF OTOH means that if the market went bull instead of bear, you would lose money instead of merely holding your position.",
"title": ""
},
{
"docid": "369266",
"text": "A stock, bond or ETF is basically a commodity. Where you bought it does not really matter, and it has a value in USD only inasmuch as there is a current market price quoted at an American exchange. But nothing prevents you from turning around and selling it on a European exchange where it is also listed for an equivalent amount of EUR (arbitrage activities of investment banks ensure that the price will be equivalent in regard to the current exchange rate). In fact, this can be used as a cheap form of currency conversion. For blue chips at least this is trivial; exotic securities might not be listed in Europe. All you need is a broker who allows you to trade on European exchanges and hold an account denominated in EUR. If necessary, transfer your securities to a broker who does, which should not cost more than a nominal fee. Mutual funds are a different beast though; it might be possible to sell shares on an exchange anyway, or sell them back to the issuer for EUR. It depends. In any case, however, transferring 7 figure sums internationally can trigger all kinds of tax events and money laundering investigations. You really need to hire a financial advisor who has international investment experience for this kind of thing, not ask a web forum!",
"title": ""
},
{
"docid": "65663",
"text": "\"@sdg's answer is spot-on with the advice to avoid repeated conversions, but I'd like to provide some specifics on the fees involved: Each time you round-trip Canadian dollars (CAD) through a U.S.-dollar (USD) priced security at TD Waterhouse and leave your proceeds in CAD, you're paying a total foreign exchange fee – implied in their rate spread – of about 3%, give or take. That's ~3% per buy & sell combination, or ~1.5% on each end. You can imagine if you trade back & forth frequently, you can quickly lose a lot of money. Do it back and forth ten times in a year and you're out ~30% on the fees alone! The TD U.S. Money Market Fund (TDB166) that TD Waterhouse is referring to has no direct commission to buy or sell, but it does have a Management Expense Ratio (MER) of 0.20% per year – basically a fee which is deducted from the fund's returns (which, today, are also close to zero.) Practically speaking, that's a very slim fee to hold some USD in your Canadian dollar TFSA. While 0.20% is cheap, a point to keep in mind is if you maintain a significant USD balance, you are maintaining currency risk: You can lose money in CAD terms if the CAD appreciates vs. USD. Additional references: Canadian Capitalist describes TD Waterhouse and the use of TDB166 and \"\"wash trades\"\" at How to \"\"Wash\"\" Your Trade? He's referring to RRSPs, but the same applies to TFSAs, which came out after the post was written. Canadian Couch Potato has two relevant articles: Are US-listed ETFs Really Cheaper? and Lowering Your Currency Exchange Fees.\"",
"title": ""
},
{
"docid": "84800",
"text": "\"Your broker, Ameritrade, offers a variety of Exchange Traded Funds (ETFs) that you can buy and sell with zero commission. An ETF is like a mutual fund, but you buy and sell shares the same way you buy and sell shares of stocks. From your point of view, the relevance of this is that you can buy and sell as many or as few shares as you like, even down to a single share. Note that to get the commission-free trades on the available ETFs you have to sign up for it in your account profile. Be sure to do that before you enter any buy orders. You'll want to start by looking at the Ameritrade's list of commission-free ETFs. Notice that they are divided into different categories: stocks, bonds, international, and commodities. Which categories you pick from will depend on your personal investing goals, time horizon, risk tolerance, and so on. There are lots of questions and answers on this site that talk about asset allocation. You should read them, as it is the most important decision you will make with your portfolio. The other thing you want to be aware of is the expense ratio for each fund. These expenses reduce the fund's return (they are included in the calculation of the net asset value of the shares), so lower is definitely better. Personally, I wouldn't even consider paying more than about 0.10% (commonly read \"\"10 basis points\"\" or \"\"10 bp\"\") for a broad-based domestic stock fund. For a sectoral fund you might put up with as much as 20 bp in expenses. Bond funds tend to be a little more expensive, so maybe allow as much as 25 bp, and likewise for international funds. I've never invested in commodity funds, so I'll let someone else opine on appropriate expense ratios for those. Once you've decided what funds you want (and have signed up for commission-free trades), all you have to do is enter the trade orders. The website where you manage your account has tutorials on how to do that. After that you should be all set. Good luck with your investing!\"",
"title": ""
},
{
"docid": "224765",
"text": "\"An ETF does not track any one individual stock. It \"\"is a marketable security that tracks an index, a commodity, bonds, or a basket of assets like an index fund.\"\" Check out this link to learn more about ETFs. The easiest way see what ETF tracks a stock is to determine what sector and industry that company is in and find some ETF that trade it. The ETF will likely trade that stock, assuming that its market cap and exchange it trades on fits within the parameters of the ETF.\"",
"title": ""
},
{
"docid": "151203",
"text": "A derivative in finance is simply any asset whose value is based on the value of another asset or based on the value of a group of assets. A derivative contract is a type of contract (usually a 'standardized contract') with specific payout instruction based on the price changes of a different asset. The basic idea is that it becomes easier to make a claim to an asset or property (and profit from this claim), without needing to physically transfer it (or even the title to said asset), and use much less capital to do so (reduce risk). They become problematic when multiple people may have claims to the real asset, or when the value of the derivatives changes very quickly or are hard to calculate. There are also liquidity problems the further you get from the real asset. This is not a problem for all kinds of derivatives contracts. And you must recognize that derivatives are used colloquially in a way that has nothing to do with reality to cause fear in people/investors that are not financially savvy. Many derivatives also have dubious or no economic purposes such that regulators don't allow them to be traded since they can't see how it is different from gambling. This is seen in financial markets that are less liberalized or cultures with puritanical backgrounds. Typically the trick is to convince regulators that the derivative or financial product helps with reducing risk and hedging and it will get approved. I've mentioned some terminology, but this depends specifically on what kind of derivatives contract you become interested in. Swaps, Credit Default Swaps, Futures, Options, Options on Futures, Leveraged Exchange Traded Funds, Inverse Leveraged Exchange Traded Funds, warrants, and more all have their own terminology. How to trade them in a simulation? It all depends on which financial product you really become interested in.",
"title": ""
},
{
"docid": "276983",
"text": "You haven't looked very far if you didn't find index tracking exchange-traded funds (ETFs) on the Toronto Stock Exchange. There are at least a half dozen major exchange-traded fund families that I'm aware of, including Canadian-listed offerings from some of the larger ETF providers from the U.S. The Toronto Stock Exchange (TSX) maintains a list of ETF providers that have products listed on the TSX.",
"title": ""
},
{
"docid": "515643",
"text": "So, couple of things. Firstly, every international ETF includes risk disclosure language in the prospectus covering both market disruption events as well as geopolitical risk, so the sponsor would be pretty well insulated from direct liability for anything. If the Russian market were truly shut down there are true-up mechanisms in place but in the scenario you're describing the market is still open, it's just only a few participants can trade in it. First thing to do is shut down creates- that is, allow no new money to come into the fund. This at least prevents your problem from getting bigger. Second you're going to switch all redemptions to in kind only. MV itself can't trade in the underlying so they're kind of jammed here. An ETF sponsor can't really refuse your redemption request (can delay, but only for a short time), but they can control the form in which they respond to it. What theoretically should happen here is an AP not subject to sanctions will step in and handle redemptions. Issue is, they'll probably charge for this so you should expect the fund to start trading at a discount to NAV (you, as an investor, sell to them cheaply, they submit a redemption request, then sell the stocks locally). Someone else has pointed that market makers will start stat arbing the fund using correlated/substitute instruments, which totally will help keep things in line, but my guess is that you'd still see the name trading away from NAV regardless. Driver of this will be the amount of money desperate to get out - if investors are content to wait the sanctions out who knows.",
"title": ""
},
{
"docid": "205280",
"text": "\"According to what little information is available currently, this fund is most akin to an actively managed exchange traded fund rather than an investment trust. An investment trust is an actively managed, closed-end fund that is tradeable on the stock market. \"\"Closed-end\"\" means that there are a fixed number of shares available for trading, so if you wish to buy or sell shares in a closed-end fund you need to find someone willing to sell or buy shares. \"\"Actively managed\"\" means that the assets are selected by the fund managers in the belief that they will perform well. This is in contrast to a \"\"passively managed\"\" fund which simply tracks an underlying index. The closed-end nature of investment trusts means that the share price is not well correlated to the value of the underlying assets. Indeed, almost all UK investment trusts trade at a significant discount to their net asset value. This reflects their historic poor performance and relatively weak liquidity. Of course there are some exceptions to this. Examples of open-end funds are unit trust (US = mutual funds) and ETFs (exchange traded funds). They are \"\"open-end\"\" funds in the sense that the number of shares/units available will change according to demand. Most importantly, the price of a share/unit will be strongly correlated to the net asset value of the underlying portfolio. In general, for an open-end fund, if the net asset value of the fund is X and there are Y shares/units outstanding, then the price of a share/unit will be X/Y. Historic data shows that passively managed funds (index trackers) \"\"always\"\" outperform actively managed funds in the long term. One of the big issues with actively managed funds is they have relatively high management fees. The Peoples Trust will be charging about 1% with a promise that this should come down over time. Compare this to a fee of 0.05% on a large, major market index tracking ETF. Further, the 1% headline fee being touted by Peoples Trust is a somewhat misleading, since they are paying their employees bonuses with shares in the fund. This will cause dilution of the net asset value per share and can be read as addition management fees by proxy. Since competent fund managers will demand high incomes, bonus shares could easily double the management fees, depending on the size of the fund. In summary, history has shown that the promises of active fund managers rarely (if ever) come to fruition. Personally, I would not consider this to be an attractive investment and would look more towards a passively managed major market index ETF with low management fees.\"",
"title": ""
},
{
"docid": "479420",
"text": "Mutual funds buy (and sell) shares in companies in accordance with the policies set forth in their prospectus, not according to the individual needs of an investor, that is, when you invest money in (or withdraw money from) a mutual fund, the manager buys or sells whatever shares that, in the manager's judgement, will be the most appropriate ones (consistent with the investment policies). Thus, a large-cap mutual fund manager will not buy the latest hot small-cap stock that will likely be hugely profitable; he/she must choose only between various large capitalization companies. Some exchange-traded funds are fixed baskets of stocks. Suppose you will not invest in a company X as a matter of principle. Unless a mutual fund prospectus says that it will not invest in X, you may well end up having an investment in X at some time because the fund manager bought shares in X. With such an ETF, you know what is in the basket, and if the basket does not include stock in X now, it will not own stock in X at a later date. Some exchange-traded funds are constructed based on some index and track the index as a matter of policy. Thus, you will not be investing in X unless X becomes part of the index because Standard or Poor or Russell or somebody changed their minds, and the ETF buys X in order to track the index. Finally, some ETFs are exactly like general mutual funds except that you can buy or sell ETF shares at any time at the price at the instant that your order is executed whereas with mutual funds, the price of the mutual fund shares that you have bought or sold is the NAV of the mutual fund shares for that day, which is established based on the closing prices at the end of the trading day of the stocks, bonds etc that the fund owns. So, you might end up owning stock in X at any time based on what the fund manager thinks about X.",
"title": ""
},
{
"docid": "322725",
"text": "In the past 10 years there have been mutual funds that would act as a single bucket of stocks and bonds. A good example is Fidelity's Four In One. The trade off was a management fee for the fund in exchange for having to manage the portfolio itself and pay separate commissions and fees. These days though it is very simple and pretty cheap to put together a basket of 5-6 ETFs that would represent a balanced portfolio. Whats even more interesting is that large online brokerage houses are starting to offer commission free trading of a number of ETFs, as long as they are not day traded and are held for a period similar to NTF mutual funds. I think you could easily put together a basket of 5-6 ETFs to trade on Fidelity or TD Ameritrade commission free, and one that would represent a nice diversified portfolio. The main advantage is that you are not giving money to the fund manager but rather paying the minimal cost of investing in an index ETF. Overall this can save you an extra .5-1% annually on your portfolio, just in fees. Here are links to commission free ETF trading on Fidelity and TD Ameritrade.",
"title": ""
},
{
"docid": "328699",
"text": "\"The London Stock Exchange offers a wealth of exchange traded products whose variety matches those offered in the US. Here is a link to a list of exchange traded products listed on the LSE. The link will take you to the list of Vanguard offerings. To view those offered by other managers, click on the letter choices at the top of the page. For example, to view the iShares offerings, click on \"\"I\"\". In the case of Vanguard, the LSE listed S&P500 ETF is traded under the code VUSA. Similarly, the Vanguard All World ETF trades under the code VWRL. You will need to be patient viewing iShares offerings since there are over ten pages of them, and their description is given by the abbreviation \"\"ISH name\"\". Almost all of these funds are traded in GBP. Some offer both currency hedged and currency unhedged versions. Obviously, with the unhedged version you are taking on additional currency risk, so if you wish to avoid currency risk then choose a currency hedged version. Vanguard does not appear to offer currency hedged products in London while iShares does. Here is a list of iShares currency hedged products. As you can see, the S&P500 currency hedged trades under the code IGUS while the unhedged version trades under the code IUSA. The effects of BREXIT on UK markets and currency are a matter of opinion and difficult to quantify currently. The doom and gloom warnings of some do not appear to have materialised, however the potential for near-term volatility remains so longs as the exit agreement is not formalised. In the long-term, I personally believe that BREXIT will, on balance, be a positive for the UK, but that is just my opinion.\"",
"title": ""
},
{
"docid": "454224",
"text": "A mutual fund has several classes of shares that are charged different fees. Some shares are sold through brokers and carry a sales charge (called load) that compensates the broker in lieu of a fee that the broker would charge the client for the service. Vanguard does not have sales charge on its funds and you don't need to go through a broker to buy its shares; you can buy directly from them. Admiral shares of Vanguard funds are charged lower annual expenses than regular shares (yes, all mutual funds charge expenses for fund adninistration that reduce the return that you get, and Vanguard has some of the lowest expense ratios) but Admiral shares are available only for large investments, typically $50K or so. If you have invested in a Vanguard mutual fund, your shares can be set to automatically convert to Admiral shares when the investment reaches the right level. A mutual fund manager can buy and sell stocks to achieve the objectives of the fund, so what stockes you are invested in as a share holder in a mutual fund will typically be unknown to you on a day-to-day basis. On the other hand, Exchange-traded funds (ETFs) are fixed baskets of stocks, and you can buy shares in the ETF. These shares are bought and sold through a broker (so you pay a transaction fee each time) but expenses are lower since there is no manager to buy and sell stocks: the basket is fixed. Many ETFs follow specific market indexes (e.g. S&P 500). Another difference between ETFs and mutual funds is that you can buy and sell ETFs at any time of the day just as if you could if you held stocks. With mutual funds, any buy and sell requests made during the day are processed at the end of the day and the value of the shares that you buy or sell is determined by the closing price of the stocks held by the mutual fund. With ETFs, you are getting the intra-day price at the time the buy or sell order is executed by your broker.",
"title": ""
},
{
"docid": "183898",
"text": "It is true that this is possible, however, it's very remote in the case of the large and reputable fund companies such as Vanguard. FDIC insurance protects against precisely this for bank accounts, but mutual funds and ETFs do not have an equivalent to FDIC insurance. One thing that does help you in the case of a mutual fund or ETF is that you indirectly (through the fund) own actual assets. In a cash account at a bank, you have a promise from the bank to pay, and then the bank can go off and use your money to make loans. You don't in any sense own the bank's loans. With a fund, the fund company cannot (legally) take your money out of the fund, except to pay the expense ratio. They have to use your money to buy stocks, bonds, or whatever the fund invests in. Those assets are then owned by the fund. Legally, a mutual fund is a special kind of company defined in the Investment Company Act of 1940, and is a separate company from the investment advisor (such as Vanguard): http://www.sec.gov/answers/mfinvco.htm Funds have their own boards, and in principle a fund board can even fire the company advising the fund, though this is not likely since boards aren't usually independent. (a quick google found this article for more, maybe someone can find a better one: http://www.marketwatch.com/story/mutual-fund-independent-board-rule-all-but-dead) If Vanguard goes under, the funds could continue to exist and get a new adviser, or could be liquidated with investors receiving whatever the assets are worth. Of course, all this legal stuff doesn't help you with outright fraud. If a fund's adviser says it bought the S&P 500, but really some guy bought himself a yacht, Madoff-style, then you have a problem. But a huge well-known ETF has auditors, tons of different employees, lots of brokerage and exchange traffic, etc. so to me at least it's tough to imagine a risk here. With a small fund company with just a few people - and there are lots of these! - then there's more risk, and you'd want to carefully look at what independent agent holds their assets, who their auditors are, and so forth. With regular mutual funds (not ETFs) there are more issues with diversifying across fund companies: With ETFs, there probably isn't much downside to diversifying since you could buy them all from one brokerage account. Maybe it even happens naturally if you pick the best ETFs you can find. Personally, I would just pick the best ETFs and not worry about advisor diversity. Update: maybe also deserving a mention are exchange-traded notes (ETNs). An ETN's legal structure is more like the bank account, minus the FDIC insurance of course. It's an IOU from the company that runs the ETN, where they promise to pay back the value of some index. There's no investment company as with a fund, and therefore you don't own a share of any actual assets. If the ETN's sponsor went bankrupt, you would indeed have a problem, much more so than if an ETF's sponsor went bankrupt.",
"title": ""
}
] |
PLAIN-1513
|
lima beans
|
[
{
"docid": "MED-4509",
"text": "Hypercholesterolemia is a major modifiable risk factor for cardiovascular disease. Some, but not all, studies have shown that soy protein intake decreases total and low-density lipoprotein cholesterol and triglycerides and increases high-density lipoprotein cholesterol. The objective of this meta-analysis was to examine the effect of soy protein supplementation on serum lipid levels in adults. English language articles were retrieved by searching MEDLINE (1966 to February 2005) and the bibliographies of the retrieved articles. A total of 41 randomized controlled trials in which isolated soy protein supplementation was the only intervention and the net changes in serum lipids during intervention were reported. Information on study design, sample size, participant characteristics, intervention, follow-up duration, and treatment outcomes was independently abstracted using a standardized protocol. Using a random-effects model, data from each study were pooled and weighted by the inverse of their variance. Soy protein supplementation was associated with a significant reduction in mean serum total cholesterol (-5.26 mg/dl, 95% confidence interval [CI] -7.14 to -3.38), low-density lipoprotein cholesterol (-4.25 mg/dl, 95% CI -6.00 to -2.50), and triglycerides (-6.26 mg/dl, 95% CI -9.14 to -3.38) and a significant increase in high-density lipoprotein cholesterol (0.77 mg/dl, 95% CI 0.20 to 1.34). Meta-regression analyses showed a dose-response relation between soy protein and isoflavone supplementation and net changes in serum lipids. These results indicate that soy protein supplementation reduces serum lipids among adults with or without hypercholesterolemia. In conclusion, replacing foods high in saturated fat, trans-saturated fat, and cholesterol with soy protein may have a beneficial effect on coronary risk factors.",
"title": "A meta-analysis of the effect of soy protein supplementation on serum lipids."
},
{
"docid": "MED-4510",
"text": "Background and Aims Studies evaluating the effect of legume consumption on cholesterol have focused on soybeans, however non-soy legumes, such as a variety of beans, peas, and some seeds, are commonly consumed in Western countries. We conducted a meta-analysis of randomized controlled trials evaluating the effects of non-soy legume consumption on blood lipids. Methods and Results Studies were retrieved by searching MEDLINE (from January 1966 through July 2009), EMBASE (from January 1980 to July 2009), and the Cochrane Collaboration's Central Register of Controlled Clinical Trials using the following terms as medical subject headings and keywords: fabaceae not soybeans not isoflavones and diet or dietary fiber and cholesterol or hypercholesterolemia or triglycerides or cardiovascular diseases. Bibliographies of all retrieved articles were also searched. From 140 relevant reports, 10 randomized clinical trials were selected which compared a non-soy legume diet to control, had a minimum duration of 3 weeks, and reported blood lipid changes during intervention and control. Data on sample size, participant characteristics, study design, intervention methods, duration, and treatment results were independently abstracted by 2 investigators using a standardized protocol. Data from 10 trials representing 268 participants were examined using a random-effects model. Pooled mean net change in total cholesterol for those treated with a legume diet compared to control was −11.8 mg/dL (95% confidence interval [CI], −16.1 to −7.5); mean net change in low density lipoprotein cholesterol was −8.0 mg/dL (95% CI, −11.4 to −4.6). Conclusion These results indicate that a diet rich in legumes other than soy decreases total and LDL cholesterol.",
"title": "Non-Soy Legume Consumption Lowers Cholesterol Levels: A Meta-Analysis of Randomized Controlled Trials"
}
] |
[
{
"docid": "MED-3170",
"text": "Background Few studies have focused on the cognitive morbidity of neurocysticercosis (NCC), one of the most common parasitic infections of the central nervous system. We longitudinally assessed the cognitive status and quality of life (QoL) of patients with incident symptomatic NCC cases and matched controls. Methodology/Principal Findings The setting of the study was the Sabogal Hospital and Cysticercosis Unit, Department of Transmissible Diseases, National Institute of Neurological Sciences, Lima, Peru. The design was a longitudinal study of new onset NCC cases and controls. Participants included a total of 14 patients with recently diagnosed NCC along with 14 healthy neighborhood controls and 7 recently diagnosed epilepsy controls. A standardized neuropsychological battery was performed at baseline and at 6 months on NCC cases and controls. A brain MRI was performed in patients with NCC at baseline and 6 months. Neuropsychological results were compared between NCC cases and controls at both time points. At baseline, patients with NCC had lower scores on attention tasks (p<0.04) compared with epilepsy controls but no significant differences compared to healthy controls. Six months after receiving anti-parasitic treatment, the NCC group significantly improved on tasks involving psychomotor speed (p<0.02). QoL at baseline suggested impaired mental function and social function in both the NCC and epilepsy group compared with healthy controls. QoL gains in social function (p = 0.006) were noted at 6 months in patients with NCC. Conclusions/Significance Newly diagnosed patients with NCC in this sample had mild cognitive deficits and more marked decreases in quality of life at baseline compared with controls. Improvements were found in both cognitive status and quality of life in patients with NCC after treatment. Author Summary Neurocysticercosis (NCC) is one of the most common parasitic infections of the central nervous system. Cognitive changes have been frequently reported with this disease but have not been well studied. Our study team recruited a group of new onset NCC cases and a matched set of healthy neighborhood controls and new onset epilepsy controls in Lima, Peru for this study. A neuropsychological battery was administered at baseline and at 6 months to all groups. Brain MRI studies were also obtained on NCC cases at baseline and at 6 months. Newly diagnosed patients with NCC had mild cognitive deficits and more marked decreases in quality of life at baseline compared with controls. Improvements were found in both cognitive status and quality of life in patients with NCC after treatment. This study is the first to assess cognitive status and quality of life longitudinally in patients with NCC and provides new data on an important clinical morbidity outcome.",
"title": "Cognitive Changes and Quality of Life in Neurocysticercosis: A Longitudinal Study"
},
{
"docid": "MED-3584",
"text": "Background: A high intake of white rice is associated with the metabolic syndrome and type 2 diabetes. Costa Ricans follow a staple dietary pattern that includes white rice and beans, yet the combined role of these foods on cardiometabolic risk factors has not been studied. Objective: We aimed to determine the association between intake of white rice and beans and the metabolic syndrome and its components in Costa Rican adults (n = 1879) without diabetes. Design: Multivariate-adjusted means were calculated for components of the metabolic syndrome by daily servings of white rice and beans (<1, 1, or >1) and by the ratio of beans to white rice. The OR for the metabolic syndrome was calculated by substituting one serving of beans for one serving of white rice. Results: An increase in daily servings of white rice was positively associated with systolic blood pressure (BP), triglycerides, and fasting glucose and inversely associated with HDL cholesterol (P-trend <0.01 for all). An increase in servings of beans was inversely associated with diastolic BP (P = 0.049). Significant trends for higher HDL cholesterol and lower BP and triglycerides were observed for 1:3, 1:2, 1:1, and 2:1 ratios of beans to white rice. Substituting one serving of beans for one serving of white rice was associated with a 35% (95% CI: 15%, 50%) lower risk of the metabolic syndrome. Conclusion: Increasing the ratio of beans to white rice, or limiting the intake of white rice by substituting beans, may lower cardiometabolic risk factors.",
"title": "A higher ratio of beans to white rice is associated with lower cardiometabolic risk factors in Costa Rican adults"
},
{
"docid": "MED-2140",
"text": "Background Around the world, beans and rice are commonly consumed together as a meal. With type 2 diabetes increasing, the effect of this traditional diet pattern on glycemic response has not been studied fully. Methods We evaluated the glycemic response of bean and rice traditional meals compared to rice alone in adults with type 2 diabetes. Seventeen men and women with type 2 diabetes controlled by metformin (n = 14) or diet/exercise (n = 3) aged 35–70 years participated in the randomized 4 × 4 crossover trial. The white long grain rice control, pinto beans/rice, black beans/rice, red kidney beans/rice test meals, matched for 50 grams of available carbohydrate, were consumed at breakfast after a 12 hour fast. Capillary blood glucose concentrations at baseline and at 30 minute intervals up to 180 minutes postprandial were collected. MANOVA for repeated measures established glucose differences between treatments. Paired t tests identified differences between bean types and the rice control following a significant MANOVA. Results Postprandial net glucose values were significantly lower for the three bean/rice treatments in contrast to the rice control at 90, 120 and 150 minutes. Incremental area under the curve values were significantly lower for the pinto and black bean/rice meals compared to rice alone, but not for kidney beans. Conclusions Pinto, dark red kidney and black beans with rice attenuate the glycemic response compared to rice alone. Promotion of traditional foods may provide non-pharmaceutical management of type 2 diabetes and improve dietary adherence with cultural groups. Trial registration Clinical Trials number NCT01241253",
"title": "Bean and rice meals reduce postprandial glycemic response in adults with type 2 diabetes: a cross-over study"
},
{
"docid": "MED-4991",
"text": "BACKGROUND: Epidemiological studies have shown positive findings associated with legume consumption and measures of cardiovascular disease and obesity. However, few observational trials have examined beans as a separate food variable when determining associations with health parameters. OBJECTIVE: To determine the association of consuming beans on nutrient intakes and physiological parameters using the National Health and Examination Survey (NHANES) 1999-2002. METHODS: Using data from NHANES 1999-2002, a secondary analysis was completed with a reliable 24-hour dietary recall where three groups of bean consumers were identified (N = 1,475). We determined mean nutrient intakes and physiological values between bean consumers and non-consumers. Least square means, standard errors and ANOVA were calculated using appropriate sample weights following adjustment for age, gender, ethnicity and energy. RESULTS: Relative to non-consumers, bean consumers had higher intakes of dietary fiber, potassium, magnesium, iron, and copper (p's < 0.05). Those consuming beans had a lower body weight (p = 0.008) and a smaller waist size (p = 0.043) relative to non-consumers. Additionally, consumers of beans had a 23% reduced risk of increased waist size (p = 0.018) and a 22% reduced risk of being obese (p = 0.026). Also, baked bean consumption was associated with a lower systolic blood pressure. CONCLUSIONS: Bean consumers had better overall nutrient intake levels, better body weights and waist circumferences, and lower systolic blood pressure in comparison to non-consumers. These data support the benefits of bean consumption on improving nutrient intake and health parameters.",
"title": "Bean consumption is associated with greater nutrient intake, reduced systolic blood pressure, lower body weight, and a smaller waist circumference ..."
},
{
"docid": "MED-3138",
"text": "Background Many consumers avoid eating beans because they believe legume consumption will cause excessive intestinal gas or flatulence. An increasing body of research and the 2010 Dietary Guidelines for Americans supports the benefits of a plant-based diet, and legumes specifically, in the reduction of chronic disease risks. The purpose of the current research was to investigate the perception of increased flatulence and gastrointestinal discomfort among participants who consumed a ½ cup of beans daily for 8 or 12 weeks. Methods Participants in three studies to test the effects of beans on heart disease biomarkers completed the same weekly questionnaire to assess gastrointestinal discomfort issues such as increased flatulence, stool changes, and bloating. Studies 1 and 2 were randomized crossover trials. Participants consumed ½ cup of pinto beans, black-eyed peas, and canned carrots as control (n = 17) in Study 1 for three randomized 8-week phases. For Study 2, participants ate ½ cup baked beans or canned carrots as control (n = 29) for two randomized 8-week phases. Study 3 was a parallel arm trial with 40 subjects receiving ½ cup pinto beans and 40 consuming a control soup for 12 weeks. Changes in the frequency of perceived flatulence, stool characteristics, and bloating were the primary outcome measures. Chi-square distributions were examined for the presence or absence of symptoms and demographic characteristics to determine differences by gender, age, body mass index (BMI), and bean type. Results Less than 50% reported increased flatulence from eating pinto or baked beans during the first week of each trial, but only 19% had a flatulence increase with black-eyed peas. A small percentage (3-11%) reported increased flatulence across the three studies even on control diets without flatulence-producing components. Conclusions People's concerns about excessive flatulence from eating beans may be exaggerated. Public health nutritionists should address the potential for gastrointestinal discomfort when increasing fiber intake from beans with clients. It is important to recognize there is individual variation in response to different bean types.",
"title": "Perceptions of flatulence from bean consumption among adults in 3 feeding studies"
},
{
"docid": "MED-1880",
"text": "Legumes are the basés diet in several countries. They hold a high nutritional value, but other properties related to human health are nowadays being studied. The aim of this work was to study the influence of processes (boiling or germination) on the phenolic composition of dark beans (Phaseolus vulgaris L. c.v. Tolosana) and their effect on their antioxidant, neuroprotective and anticancer ability. Phenolic composition of raw and processed dark beans was analysed by HPLC-PAD and HPLC-ESI/MS. The antioxidant activity was evaluated by ORAC. Astrocytes cultures (U-373) have been used to test their neuroprotective effect. Anticancer activities were evaluated on three different cell lines (renal adenocarcinoma (TK-10), breast adenocarcinoma (MCF-7) and melanoma (UACC-62)) by sulphorhodamine B method. Qualitative and quantitative differences in phenolic composition have been observed between raw and processed dark beans that influence the antioxidant activity, mainly for germinated samples which show a decrease of antioxidant capacity. Although every assayed extracts decreased reactive oxygen species release and exhibited cytotoxicity activities on cancer cell lines, raw beans proved to be the most active in neuroprotective and antitumoral effects; this sample is especially rich in phenolic compounds, mainly anthocyanins. This study further demonstrated that phenolic composition of dark beans is related with cooking process and so with their neuroprotective and anticancer activity; cooking of dark beans improves their digestion and absorption at intestinal level, while maintaining its protective ability on oxidative process at cellular level. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Effect of cooking and germination on phenolic composition and biological properties of dark beans (Phaseolus vulgaris L.)."
},
{
"docid": "MED-3141",
"text": "OBJECTIVE: To evaluate the associations with chronic disease risk and mortality of the consequences of bean-free diets in Taiwanese adults with regard to gender. DESIGN: A sub-sample of the National Health Interview Survey (NHIS) in 2001 agreed to physical examination in the subsequent year. This group then took part in the Taiwanese Survey of Hyperglycaemia, Hyperlipidaemia and Hypertension (TwSHHH) in 2002. SETTING: Individual records were linked to the eventual death files from 2002 to 2008. SUBJECTS: Up to the end of 2008, a total of 2820 men and 2950 women were tracked by death registry over the 6·8 years of follow-up. RESULTS: Among 38,077 person-years, an average follow-up 6·5 years, 225 all-cause deaths were identified. Generalized linear models showed beans to be favourable for metabolic syndrome (other than for fasting glucose) in men; in women, beans were favourable for waist circumference and HbA1c. Cumulative logistic regression models for the effect of a bean-free diet on metabolic syndrome scores according to the Taiwanese-modified National Cholesterol Education Program-Adult Treatment Panel III (NCEP-tw) gave adjusted odds ratios of 1·83 in men and 1·45 in women. Cox regression models for the bean-free diet showed an increased hazard ratio for all-cause mortality among women (1·98, 95% CI 1·03, 3·81) but not men (1·28, 95% CI 0·76, 2·16). CONCLUSIONS: A bean-free diet may play a role in developing the metabolic syndrome in both genders, and is a significant predictor of all-cause mortality in Taiwanese women but not men.",
"title": "A bean-free diet increases the risk of all-cause mortality among Taiwanese women: the role of the metabolic syndrome."
},
{
"docid": "MED-5079",
"text": "OBJECTIVE: To determine effects of daily intake of 1/2 cup pinto beans, black-eyed peas or carrots (placebo) on risk factors for coronary heart disease (CHD) and diabetes mellitus (DM) in free-living, mildly insulin resistant adults over an 8 week period. METHODS: Randomized, crossover 3x3 block design. Sixteen participants (7 men, 9 women) received each treatment for eight-weeks with two-week washouts. Fasting blood samples collected at beginning and end of periods were analyzed for total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol, triacylglycerols, high-sensitivity C-reactive protein, insulin, glucose, and hemoglobin A1c. RESULTS: A significant treatment-by-time effect impacted serum TC (p = 0.026) and LDL (p = 0.033) after eight weeks. Paired t-tests indicated that pinto beans were responsible for this effect (p = 0.003; p = 0.008). Mean change of serum TC for pinto bean, black-eyed pea and placebo were -19 +/- 5, 2.5 +/- 6, and 1 +/- 5 mg/dL, respectively (p = 0.011). Mean change of serum LDL-C for pinto bean, black-eyed pea and placebo were -14 +/- 4, 4 +/- 5, and 1 +/- 4 mg/dL, in that order (p = 0.013). Pinto beans differed significantly from placebo (p = 0.021). No significant differences were seen with other blood concentrations across the 3 treatment periods. CONCLUSIONS: Pinto bean intake should be encouraged to lower serum TC and LDL-C, thereby reducing risk for CHD.",
"title": "Pinto bean consumption reduces biomarkers for heart disease risk."
},
{
"docid": "MED-2570",
"text": "The functional properties, including antioxidant and chemopreventative capacities as well as the inhibitory effects on angiotensin-converting enzyme (ACE), α-glucosidase and pancreatic lipase, of three Australian-grown faba bean genotypes (Nura, Rossa and TF(Ic*As)*483/13) were investigated using an array of in vitro assays. Chromatograms of on-line post column derivatisation assay coupled with HPLC revealed the existence of active phenolics (hump) in the coloured genotypes, which was lacking in the white-coloured breeding line, TF(Ic*As)*483/13. Roasting reduced the phenolic content, and diminished antioxidant activity by 10-40 % as measured by the reagent-based assays (diphenylpicrylhydrazyl, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) and oxygen radical absorbance capacity) in all genotypes. Cell culture-based antioxidant activity assay (cellular antioxidant activity) showed an increase of activity in the coloured genotypes after roasting. Faba bean extracts demonstrated cellular protection ability against H₂O₂-induced DNA damage (assessed using RAW264.7 cells), and inhibited the proliferation of all human cancer cell lines (BL13, AGS, Hep G2 and HT-29) evaluated. However, the effect of faba bean extracts on the non-transformed human cells (CCD-18Co) was negligible. Flow cytometric analyses showed that faba bean extracts successfully induced apoptosis of HL-60 (acute promyelocytic leukaemia) cells. The faba bean extracts also exhibited ACE, α-glucosidase and pancreatic lipase inhibitory activities. Overall, extracts from Nura (buff-coloured) and Rossa (red-coloured) were comparable, while TF(Ic*As)*483/13 (white-coloured) contained the lowest phenolic content and exhibited the least antioxidant and enzyme inhibition activities. These results are important to promote the utilisation of faba beans in human diets for various health benefits.",
"title": "In vitro investigations of the potential health benefits of Australian-grown faba beans (Vicia faba L.): chemopreventative capacity and inhibitory ..."
},
{
"docid": "MED-3136",
"text": "The objective of this study was to determine the influence of frequent and long-term consumption of legume seeds on colonic function. Two groups of subjects were studied--one group habitually consumed legume seeds as part of their normal diet, a second group only infrequently consumed legumes. No differences between these groups could be detected for fecal output and frequency, intestinal transit time, VFA excretion or fecal pH during 23-day study periods in which subjects consumed either their usual diet or 100 g red kidney beans, daily. However, the addition of beans to the diets of both groups provided significantly more dietary fiber, and produced greater fecal output and a higher concentration of VFA in feces. Fecal output appeared to be determined by two independent parameters--dietary fiber intake and VFA excretion. Beans provided a physiologically useful source of dietary fiber and favorably influenced colonic function.",
"title": "Influence of frequent and long-term bean consumption on colonic function and fermentation."
},
{
"docid": "MED-2147",
"text": "Consumption of Phaseolus vulgaris bean species such as pinto, black, navy or kidney may be beneficial in the prevention and treatment of chronic diseases. In particular, conditions that are promoted by increased glycaemic stress (hyperglycaemia and hyperinsulinaemia) including diabetes, CVD and cancer seem to be reduced in individuals who eat more of these beans. The present paper discusses the influence of P. vulgaris species on glycaemic response and the impact that relationship may have on the risk of developing diabetes, CVD and cancer.",
"title": "Phaseolus beans: impact on glycaemic response and chronic disease risk in human subjects."
},
{
"docid": "MED-2580",
"text": "Adequate fruit and vegetable intake was suggested to protect against colorectal cancer and colorectal adenomas; however, several recent prospective studies reported no association. We examined the association between fruits and vegetables and adenomatous polyp recurrence in the Polyp Prevention Trial (PPT). The PPT was a low-fat, high-fiber, high-fruit, and vegetable dietary intervention trial of adenoma recurrence, in which there were no differences in the rate of adenoma recurrence in participants in the intervention and control arms of the trial. In this analysis of the entire PPT trial–based cohort, multiple logistic regression analysis was used to estimate the odds ratio (OR) of advanced and nonadvanced adenoma recurrence within quartiles of baseline and change (baseline minus the mean over 3 y) in fruit and vegetable intake, after adjustment for age, total energyy intake, use of nonsteroidal anti-inflammatory drugs, BMI, and gender. There were no significant associations between nonadvanced adenoma recurrence and overall change in fruit and vegetable consumption; however, those in the highest quartile of change in dry bean intake (greatest increase) compared with those in the lowest had a significantly reduced OR for advanced adenoma recurrence (OR = 0.35; 95% CI, 0.18–0.69; P for trend = 0.001). The median in the highest quartile of change in dry bean intake was 370% higher than the baseline intake. The PPT trial–based cohort provides evidence that dry beans may be inversely associated with advanced adenoma recurrence.",
"title": "High Dry Bean Intake and Reduced Risk of Advanced Colorectal Adenoma Recurrence among Participants in the Polyp Prevention Trial"
},
{
"docid": "MED-2144",
"text": "Bean pods (Phaseolus vulgaris) are among the most widely used traditional remedies against diabetes mellitus. Historical knowledge is summarized and compared to recent study results. Reports dating from the first half of the 20(th) century as well as recent publications show contradictory results. It seems that Phaseolus preparations should not be considered the first choice in phytopharmaceutical treatment of diabetes or lead structure research. To be effective, fairly high doses of aqueous extracts need to be given. Because of their fiber content and an alpha-amylase inhibitory effect, beans might be more useful as food components in preventing or ameliorating type 2 diabetes.",
"title": "Beans and diabetes: Phaseolus vulgaris preparations as antihyperglycemic agents."
},
{
"docid": "MED-2010",
"text": "Legumes (including alfalfa, clover, lupins, green beans and peas, peanuts, soybeans, dry beans, broad beans, dry peas, chickpeas, and lentils) represent an important component of the human diet in several areas of the world, especially in the developing countries, where they complement the lack of proteins from cereals, roots, and tubers. In some regions of the world, legume seeds are the only protein supply in the diet. The health benefits of legume consumption have received rising interest from researchers, and their consumption and production extends worldwide. Among European countries, higher legume consumption is observed around the Mediterranean, with per capita daily consumption between 8 and 23 g, while in Northern Europe, the daily consumption is less than 5 g per capita. The physiological effects of different legumes vary significantly. These differences may result from the polysaccharides composition, in particular, the quantity and variety of dietary fibers and starch, protein make-up, and variability in phytochemical content. The majority of legumes contain phytochemicals: bioactive compounds, including enzyme inhibitors, phytohemagglutinins (lectins), phytoestrogens, oligosaccharides, saponins, and phenolic compounds, which play metabolic roles in humans who frequently consume these foods. Dietary intake of phytochemicals may provide health benefits, protecting against numerous diseases or disorders, such as coronary heart disease, diabetes, high blood pressure and inflammation. The synergistic or antagonistic effects of these phytochemical mixtures from food legumes, their interaction with other components of the diet, and the mechanism of their action have remained a challenge with regard to understanding the role of phytochemicals in health and diseases. Their mitigating effects and the mechanism of their action need to be further addressed if we are to understand the role of phytochemicals in health and diseases. This review provides an overview of the nutritional quality of legumes and their potential contribution in cardiometabolic risk prevention.",
"title": "Nutritional quality of legumes, and their role in cardiometabolic risk prevention: a review."
},
{
"docid": "MED-5078",
"text": "In this study, solid fermentation of steamed black soybean with various GRAS (Generally recognized as safe) filamentious-fungi including Aspergillus awamori, Aspergillus oryzae BCRC 30222, Aspergillus sojae BCRC 30103, Rhizopus azygosporus BCRC 31158 and Rhizopus sp. No. 2 was performed. Mutagenicity and antimutagenicity of the methanol extracts of unfermented and fermented steamed black soybeans against 4-nitroquinoline-N-oxide (4-NQO), a direct mutagen and Benzo[a]pyrene (B[a]P), an indirect mutagen, on Salmonella Typhimurium TA100 and TA 98, were examined. The methanol extracts of unfermented and fermented steamed black soybeans show no mutagenic activity for either test strains at the doses tested. The extracts inhibited mutagenesis by either 4-NQO or B[a]P in S. Typhimurium TA100 and TA98. Fermentation with fungi also enhanced the antimutagenic effect of black soybean while the antimutagenic effect of the fermented black soybeans extract varied with the starter organism, mutagen, and test strain of S. Typhimurium examined. Generally, the extracts of A. awamori-fermented black soybean exhibited the highest antimutagenic effect. With strain TA100, the inhibitory effects of 5.0 mg of A. awamori-fermented black soybean extract per plate on the mutagenic effects of 4-NQO and B[a]P were 92% and 89%, respectively, while the corresponding rates for extract of unfermented were 41% and 63%, respectively. With strain 98, the inhibition rates were 94 and 81% for the fermented bean extract and 58% and 44% for the unfermented bean extracts. Testing of extracts prepared from black soybean by A. awamori at temperatures 25, 30 and 35 degrees C and for times of 1-5 days revealed that, generally, the extract prepared from beans fermented at 30 degrees C for 3 days exhibited the greatest inhibition against the mutagenic effects of 4-NQO and B[a]P.",
"title": "Mutagenic and antimutagenic effects of methanol extracts of unfermented and fermented black soybeans."
},
{
"docid": "MED-2141",
"text": "We investigated the association between dietary patterns and insulin resistance in the 3871 healthy Korean adults from the 2007 to 2008 Korea National Health and Nutrition Examination Survey. The whole grains and beans pattern was associated with lower prevalence of insulin resistance (OR for highest quintile=0.80, 95% CI=0.61-1.03, P for trend=0.013). Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.",
"title": "High intake of whole grains and beans pattern is inversely associated with insulin resistance in healthy Korean adult population."
},
{
"docid": "MED-5080",
"text": "Bioactivity-guided fractionation of black bean (Phaseolus vulgaris) seed coats was used to determine the chemical identity of bioactive constituents, which showed potent antiproliferative and antioxidative activities. Twenty-four compounds including 12 triterpenoids, 7 flavonoids, and 5 other phytochemicals were isolated using gradient solvent fractionation, silica gel and ODS columns, and semipreparative and preparative HPLC. Their chemical structures were identified using MS, NMR, and X-ray diffraction analysis. Antiproliferative activities of isolated compounds against Caco-2 human colon cancer cells, HepG2 human liver cancer cells, and MCF-7 human breast cancer cells were evaluated. Among the compounds isolated, compounds 1, 2, 6, 7, 8, 13, 14, 15, 16, 19, and 20 showed potent inhibitory activities against the proliferation of HepG2 cells, with EC50 values of 238.8 +/- 19.2, 120.6 +/- 7.3, 94.4 +/- 3.4, 98.9 +/- 3.3, 32.1 +/- 6.3, 306.4 +/- 131.3, 156.9 +/- 11.8, 410.3 +/- 17.4, 435.9 +/- 47.7, 202.3 +/- 42.9, and 779.3 +/- 37.4 microM, respectively. Compounds 1, 2, 3, 5, 6, 7, 8, 9, 10, 11, 14, 15, 19, and 20 showed potent antiproliferative activities against Caco-2 cell growth, with EC50 values of 179.9 +/- 16.9, 128.8 +/- 11.6, 197.8 +/- 4.2, 105.9 +/- 4.7, 13.9 +/- 2.8, 35.1 +/- 2.9, 31.2 +/- 0.5, 71.1 +/- 11.9, 40.8 +/- 4.1, 55.7 +/- 8.1, 299.8 +/- 17.3, 533.3 +/- 126.0, 291.2 +/- 1.0, and 717.2 +/- 104.8 microM, respectively. Compounds 5, 7, 8, 9, 11, 19, 20 showed potent antiproliferative activities against MCF-7 cell growth in a dose-dependent manner, with EC50 values of 129.4 +/- 9.0, 79.5 +/- 1.0, 140.1 +/- 31.8, 119.0 +/- 7.2, 84.6 +/- 1.7, 186.6 +/- 21.1, and 1308 +/- 69.9 microM, respectively. Six flavonoids (compounds 14-19) showed potent antioxidant activity. These results showed the phytochemical extracts of black bean seed coats have potent antioxidant and antiproliferative activities.",
"title": "Phytochemicals of black bean seed coats: isolation, structure elucidation, and their antiproliferative and antioxidative activities."
},
{
"docid": "MED-3132",
"text": "Little is known about dietitians current practice in counselling clients about the use of legumes in a low fat, high fibre diet. An exploratory e-mail questionnaire was sent to members of Dietitians of Canada to assess: dietitian use and preferences for legumes, dietitian practice, opinions about clients attitudes and preferences, and resource needs. Counsellors (n=256) had high personal use of legumes (64% > or = 1 serving/week) and frequently recommended legumes in counselling. The legumes most preferred by respondents and their clients were: peanuts, kidney beans, split peas, chickpeas, and lentils. Respondents often recommended canned bean products (76%) and tofu (61%), but other legume grocery products were less often recommended. The most common client issues identified were: flatulence (87% agreed), lack of familiarity (85%), and knowledge of preparation (82%). Dietitians were not satisfied with current resources to support practice, especially those respondents providing primarily clinical counselling services. The most requested resources were: recipes (90%), pamphlets (82%), food demonstrations (75%) and Internet sites (63%). Client level research is now needed to confirm the importance of the issues identified and to develop and test strategies for legume promotion in counselling.",
"title": "Legume promotion in counselling: an e-mail survey of dietitians."
},
{
"docid": "MED-2085",
"text": "A diet rich in fruits and vegetables is known to decrease the risk of cardiovascular disease. However, the information regarding the antithrombotic activity (antiplatelet, anticoagulant, and fibrinolytic) of fruits and vegetables is scarce. The aim of this study was to assess the antithrombotic activity of extracts from fruits and vegetables widely consumed in central Chile. The study included samples of 19 fruits and 26 vegetables, representative of the local diet. The extracts prepared from each sample included an aqueous (juice or pressed solubles) and/or methanol-soluble fraction. The extracts were evaluated for antiplatelet, anticoagulant, and fibrinolytic activity in vitro at a final concentration of 1 mg/ml. The antiplatelet activity was assessed by platelet aggregation inhibition; anticoagulant activity was measured by the prothrombin time (PT), diluted prothrombin time (dPT), activated partial thromboplastin time (APTT), kaolin clotting time (KCT), and thrombin time. The fibrinolytic effect was determined with the euglobin clot lysis time and fibrin plate methods. Extracts of green beans and tomatoes inhibited platelet aggregation induced by ADP and arachidonic acid, in a concentration-dependent manner. The methanolic extracts of grapes prolonged the PT and dPT. Finally, extracts of raspberry prolonged the APTT and also presented fibrinolytic activity. In conclusion, from a screening that included a variety of fruits and vegetables, we found antiplatelet activity in green beans and tomatoes, anticoagulant activities in grapes and raspberries, whereas fibrinolytic activity was observed only in raspberries. Further investigations are necessary to advance in knowledge of the active compounds of these fruits and vegetables and their mechanisms of action.",
"title": "Antiplatelet, anticoagulant, and fibrinolytic activity in vitro of extracts from selected fruits and vegetables."
},
{
"docid": "MED-5118",
"text": "OBJECTIVE: To compare the effects of two commercially available soy milks (one made using whole soy beans, the other using soy protein isolate) with low-fat dairy milk on plasma lipid, insulin, and glucose responses. DESIGN: Randomized clinical trial, cross-over design. SUBJECTS: Participants were 30-65 years of age, n = 28, with pre-study LDL-cholesterol (LDL-C) concentrations of 160-220 mg/dL, not on lipid lowering medications, and with an overall Framingham risk score of <or=10%. INTERVENTION: Participants were required to consume sufficient milk to provide 25 g protein/d from each source. The protocol included three 4-week treatment phases, each separated from the next by a wash-out period of >or=4 weeks. RESULTS: Mean LDL-C concentration at the end of each phase (+/- SD) was 161 +/- 20, 161 +/- 26 and 170 +/- 24 mg/dL for the whole bean soy milk, the soy protein isolate milk, and the dairy milk, respectively (p = 0.9 between soy milks, p = 0.02 for each soy milk vs. dairy milk). No significant differences by type of milk were observed for HDL-cholesterol, triacylglycerols, insulin, or glucose. CONCLUSION: A 25 g dose of daily soy protein from soy milk led to a modest 5% lowering of LDL-C relative to dairy milk among adults with elevated LDL-C. The effect did not differ by type of soy milk and neither soy milk significantly affected other lipid variables, insulin or glucose.",
"title": "Effect of two types of soy milk and dairy milk on plasma lipids in hypercholesterolemic adults: a randomized trial."
},
{
"docid": "MED-3894",
"text": "The purpose of this study was to examine the effects of a natural carbohydrate (CHO) source in the form of sun-dried raisins (SDRs) vs. Sports Jelly Beans™ (SJBs) on endurance performance in trained cyclists and triathletes. Ten healthy men (18-33 years) completed 1 water-only acclimatization exercise trial and 2 randomized exercise trials administered in a crossover fashion. Each trial consisted of a 120-minute constant-intensity glycogen depletion period followed by a 10-km time trial (TT). During each experimental trial, participants consumed isocaloric amounts of SDRs or SJBs in 20-minute intervals. Measurements included time to complete 10-km TT, power output during 10-km TT, blood glucose levels and respiratory exchange ratio during glycogen depletion period, rate of perceived exertion (RPE), 'flow' questionnaire responses, and a hedonic (i.e., pleasantness) sensory acceptance test. There were no significant differences in endurance performance for TT time (SDRs vs. SJBs, 17.3 ± 0.4 vs. 17.3 ± 0.4 seconds) or power (229.3 ± 13.0 vs. 232.0 ± 13.6 W), resting blood glucose levels (5.8 ± 04 mmol·L(-1) for SDRs and 5.4 ± 0.2 mmol·L(-1) for SJBs), RPE, or flow experiences between SDR and SJB trials. However, the mean sensory acceptance scores were significantly higher for the SDRs compared to the SJBs (50.7 ± 1.7 vs. 44.3 ± 2.7). Consuming SDRs or SJBs during 120 minutes of intense cycling results in similar subsequent TT performances and are equally effective in maintaining blood glucose levels during exercise. Therefore, SDRs are a natural, pleasant, cost-effective CHO alternative to commercial SJBs that can be used during moderate- to high-intensity endurance exercise.",
"title": "Sun-dried raisins are a cost-effective alternative to Sports Jelly Beans in prolonged cycling."
},
{
"docid": "MED-4869",
"text": "This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of various food additives, including flavouring agents, with a view to recommending acceptable daily intakes (ADIs) and to preparing specifications for identity and purity. The first part of the report contains a general discussion of the principles governing the toxicological evaluation and assessment of intake of food additives (in particular, flavouring agents). A summary follows of the Committee's evaluations of technical, toxicological and intake data for certain food additives (asparaginase from Aspergillus niger expressed in A. niger, calcium lignosulfonate (40-65), ethyl lauroyl arginate, paprika extract, phospholipase C expressed in Pichia pastoris, phytosterols, phytostanols and their esters, polydimethylsiloxane, steviol glycosides and sulfites [assessment of dietary exposure]) and 10 groups of related flavouring agents (aliphatic branched-chain saturated and unsaturated alcohols, aldehydes, acids and related esters; aliphatic linear alpha,beta-unsaturated aldehydes, acids and related alcohols, acetals and esters; aliphatic secondary alcohols, ketones and related esters; alkoxy-substituted allylbenzenes present in foods and essential oils and used as flavouring agents; esters of aliphatic acyclic primary alcohols with aliphatic linear saturated carboxylic acids; furan-substituted aliphatic hydrocarbons, alcohols, aldehydes, ketones, carboxylic acids and related esters, sulfides, disulfides and ethers; miscellaneous nitrogen-containing substances; monocyclic and bicyclic secondary alcohols, ketones and related esters; hydroxy- and alkoxy-substituted benzyl derivatives; and substances structurally related to menthol). Specifications for the following food additives were revised: canthaxanthin; carob bean gum and carob bean gum (clarified); chlorophyllin copper complexes, sodium and potassium salts; Fast Green FCF; guar gum and guar gum (clarified); iron oxides; isomalt; monomagnesium phosphate; Patent Blue V; Sunset Yellow FCF; and trisodium diphosphate. Re-evaluation of flavouring agents for which estimated intake was based on anticipated poundage data was carried out for 2-isopropyl- N,2,3-trimethylbutyramide (No. 1595) and L-monomenthyl glutarate (No. 1414). Annexed to the report are tables summarizing the Committee's recommendations for intakes and toxicological evaluations of the food additives considered.",
"title": "Evaluation of certain food additives."
},
{
"docid": "MED-2150",
"text": "Previous investigations, of adolescent diet recalled in adulthood, found lower risk for benign breast disease (BBD) with higher intakes of vegetable fat and nuts during high school. We investigate whether vegetable protein and fat, derived from diets reported during pre-adolescence and adolescence, are associated with subsequent risk for BBD in young women. The Growing Up Today Study includes 9,039 females, 9–15 years in 1996, who completed questionnaires annually through 2001, and then in 2003, 2005, 2007, and 2010. Food frequency questionnaires (1996–2001) obtained intake data on a variety of foods. Beginning in 2005, women (18–30 years) reported whether they had ever been diagnosed with BBD that was confirmed by breast biopsy (n = 112 cases). Logistic regression estimated associations between intakes of vegetable protein and fat and biopsy-confirmed BBD. Those individual foods that were the largest contributors of protein and fat in this cohort were also investigated. In analyses of intakes from 1996 through 1998, when our cohort was youngest, vegetable fat (OR = 0.72/(10 gm/day), 95 % CI 0.53–0.98; p = 0.04) was inversely associated with BBD risk. The greatest sources of vegetable fat and protein in these girls were peanut butter, peanuts, nuts, beans (beans, lentils, and soybeans), and corn. A daily serving of any one of these was associated with lower risk (OR = 0.32/(serv/day), 95 % CI 0.13–0.79; p = 0.01). Peanut butter (and nuts) at age 11 years was inversely associated with risk (p = 0.01). In analyses of intakes at age 14 years, vegetable protein was associated with lower BBD risk (OR = 0.64/(10 gm/day), 95 % CI 0.43–0.95; p = 0.03). A daily serving at 14 years of any one of the foods was associated with lower risk (OR = 0.34, 95 % CI 0.16–0.75; p = 0.01), as was peanut butter (and nuts) (p = 0.02). Girls with a family history of breast cancer had significantly lower risk if they consumed these foods or vegetable fat. In conclusion, consumption of vegetable protein, fat, peanut butter, or nuts by older girls may help reduce their risk of BBD as young women.",
"title": "Vegetable protein and vegetable fat intakes in pre-adolescent and adolescent girls, and risk for benign breast disease in young women"
},
{
"docid": "MED-719",
"text": "In addition to causing embarrassment and unease, flatulence is linked to a variety of symptoms, some of which may be distressing. This review describes the origins of intestinal gas, its composition and methods which have been developed for its analysis. Emphasis is placed upon the effects of legumes in the diet in producing excessive intestinal gas and, particularly, on the role of raffinose-type oligosaccharides, containing alpha-galactosidic groupings. Suggestions for overcoming the problem are presented, including drug treatment, enzyme treatment, food processing and plant breeding. It is emphasised that removal of all raffinose-oligosaccharides from beans does not remove the problem of flatulence in animals and man; the compounds responsible--though assumed to be polysaccharides (or polysaccharide-derived oligomers formed by processing or cooking)--have yet to be characterised.",
"title": "Flatulence--causes, relation to diet and remedies."
},
{
"docid": "MED-724",
"text": "In addition to causing embarrassment and unease, flatulence is linked to a variety of symptoms, some of which may be distressing. This review describes the origins of intestinal gas, its composition and methods which have been developed for its analysis. Emphasis is placed upon the effects of legumes in the diet in producing excessive intestinal gas and, particularly, on the role of raffinose-type oligosaccharides, containing alpha-galactosidic groupings. Suggestions for overcoming the problem are presented, including drug treatment, enzyme treatment, food processing and plant breeding. It is emphasised that removal of all raffinose-oligosaccharides from beans does not remove the problem of flatulence in animals and man; the compounds responsible--though assumed to be polysaccharides (or polysaccharide-derived oligomers formed by processing or cooking)--have yet to be characterised.",
"title": "Flatulence--causes, relation to diet and remedies."
},
{
"docid": "MED-890",
"text": "A case-control study was carried out in Harbin city to assess the role of diet in the aetiology of colorectal cancer. A total of 336 incident cases of histologically confirmed colorectal cancer (111 colon cancer and 225 rectal cancer) and an equal number of controls with other non-neoplastic diseases were interviewed in hospital wards. Data concerning the average frequency of consumption and amount consumed of single food items were obtained by a dietary history questionnaire. Odds ratios and their confidence limits were computed. Multiple regression for risk status was also used. Vegetables, particularly green vegetables, chives and celery, have a strong protective effect against colorectal cancer. Reduced consumption of meat, eggs, bean products and grain was associated with increasing risk for cancer of the rectum. Alcohol intake was found to be an important risk factor for developing colon cancer and male rectal cancer.",
"title": "Diet and cancer of the colon and rectum: a case-control study in China."
},
{
"docid": "MED-4165",
"text": "Ergothioneine is a native membrane-impermeable thiol compound that is specifically accumulated in cells via the organic cation transporter OCTN1. In humans, OCTN1 and ergothioneine have been implicated in the etiopathogenesis of autoimmune disorders. However, available evidence about dietary sources and the functional role of ergothioneine in human physiology is scarce. Here, we analyzed the ergothioneine content in common foods using liquid chromatography tandem-mass spectrometry. Additionally, we assessed the protective potency of ergothioneine against various oxidative stressors in OCTN1-expressing cells in comparison with the main intracellular thiol antioxidant glutathione by evaluating cell viability with the MTT reduction assay. Only some food contained ergothioneine with highest concentrations detected in specialty mushrooms, kidney, liver, black and red beans, and oat bran. Ergothioneine exhibited cell protection only against copper(II)-induced toxicity but was far less potent than glutathione, indicting that ergothioneine is not involved in the intracellular antioxidant thiol defense system.",
"title": "Dietary sources and antioxidant effects of ergothioneine."
},
{
"docid": "MED-875",
"text": "AIMS: The purpose of this study was to search for a novel quorum sensing inhibitor and analyse its inhibitory activity. METHODS AND RESULTS: Quorum sensing inhibition was monitored using the Tn-5 mutant, Chromobacterium violaceum CV026. Vanilla beans (Vanilla planifolia Andrews) were extracted using 75% (v/v) aqueous methanol and added to C. violaceum CV026 cultures. Inhibitory activity was measured by quantifying violacein production using a spectrophotometer. The results have revealed that vanilla extract significantly reduced violacein production in a concentration-dependent manner, indicating inhibition of quorum sensing. CONCLUSIONS: Vanilla, a widely used spice and flavour, can inhibit bacterial quorum sensing. SIGNIFICANCE AND IMPACT OF THE STUDY: The results suggest that the intake of vanilla-containing food materials might promote human health by inhibiting quorum sensing and preventing bacterial pathogenesis. Further studies are required to isolate specific substances from vanilla extract acting as quorum sensing inhibitors.",
"title": "Inhibition of bacterial quorum sensing by vanilla extract."
},
{
"docid": "MED-5354",
"text": "This review focuses on the possible role in human health of the consumption of lignan-rich foods. Most of the plant lignans in human foods are converted by the intestinal microflora in the upper part of the large bowel to enterolactone and enterodiol, called mammalian or enterolignans. The protective role of these compounds, particularly in chronic Western diseases, is discussed. Evidence suggests that fiber- and lignan-rich whole-grain cereals, beans, berries, nuts, and various seeds are the main protective foods. Many factors, in addition to diet, such as intestinal microflora, smoking, antibiotics, and obesity affect circulating lignan levels in the body. Lignan-rich diets may be beneficial, particularly if consumed for life. Experimental evidence in animals has shown clear anticarcinogenic effects of flaxseed or pure lignans in many types of cancer. Many epidemiological results are controversial, partly because the determinants of plasma enterolactone are very different in different countries. The source of the lignans seems to play a role because other factors in the food obviously participate in the protective effects. The results are promising, but much work is still needed in this area of medicine.",
"title": "Lignans and human health."
},
{
"docid": "MED-2195",
"text": "The objective of this study was to evaluate the precursors of acrylamide formation in sweet potato (SP) (Ipomoea batatas L. Lam) chips and to determine the effect of different types of vegetable oils (VOs), that is, palm olein, coconut oil, canola oil, and soya bean oil, on acrylamide formation. The reducing sugars and amino acids in the SP slices were analyzed, and the acrylamide concentrations of SP chips were measured. SP chips that were fried in a lower degree of unsaturation oils contained a lower acrylamide concentration (1443 μg/kg), whereas those fried with higher degree of unsaturated oils contained a higher acrylamide concentration (2019 μg/kg). SP roots were found to contain acrylamide precursors, that is, 4.17 mg/g glucose and 5.05 mg/g fructose, and 1.63 mg/g free asparagine. The type of VO and condition used for frying, significantly influenced acrylamide formation. This study clearly indicates that the contribution of lipids in the formation of acrylamide should not be neglected. © 2013 Institute of Food Technologists®",
"title": "The influence of deep frying using various vegetable oils on acrylamide formation in sweet potato (Ipomoea batatas L. Lam) chips."
}
] |
8738
|
When to convert employee shares in an RRSP into cash, even if there is a penalty?
|
[
{
"docid": "432511",
"text": "The cost to you for selling is 3/8% of a years salary, this is what you won't get if you sell. Tough to calculate the what-if scenarios beyond this, since I can't quantify the risk of a price drop. Once the amount in he stock is say,10%, of a years salary, if you know a drop is coming, a sale is probably worth it, for a steep drop. My stronger focus would be on how much of your wealth is concentrated in that one stock, Enron, and all.",
"title": ""
}
] |
[
{
"docid": "432902",
"text": "\"Your question is based on incorrect assumptions. Generally, there's no \"\"penalty\"\", per se, to make a withdrawal from your RRSP, even if you make a withdrawal earlier than retirement, however you define it. A precise meaning for \"\"retirement\"\" with respect to RRSPs is largely irrelevant.* Our U.S. neighbours have a 10% penalty on non-hardship early withdrawals (before age 59 ½) from retirement accounts like the 401k and IRA. It's an additional measure designed to discourage early withdrawals, and raise more tax. Yet, in Canada, there is no similar penalty. Individual investments inside your RRSP may have associated penalties, such as the dreaded \"\"deferred sales charge\"\" (DSC) of some back-end loaded mutual funds, or such as LSVCC funds that generated additional special tax credits that could get clawed back. Yet, these early withdrawal penalties are distinct from the RRSP nature of your account. Choose your investments carefully to avoid these kinds of surprises. Rather, an RRSP is a tax-deferred account, and it works like this: The government allows you to claim a nice juicy tax deduction, which can reduce your income tax at your marginal rate in the year you make a contribution, or later if you should choose to defer the deduction. The resulting pre-tax money accumulated in your RRSP benefits from further tax deferral: assets can grow without attracting annual income tax on earned interest, dividends, or capital gains. You don't need to declare on your income tax return any of the income earned inside your RRSP, unlike a regular investment account. Here's the rub: Once you decide to withdraw money from your RRSP, the entire amount withdrawn is considered regular income in the year in which you make the withdrawal. Thus, your withdrawals are subject to income tax, and yes, at your marginal rate. This is always the case, whether before or after retirement. You mentioned two special programs: The Home Buyers' Plan (HBP), and the Lifelong Learning Plan (LLP). Neither the HBP nor the LLP permit tax-free withdrawals. Rather, each of these programs are special kinds of loans that you can borrow from your own RRSP. HBP and LLP loan money isn't taxed when you get it because you are required to pay it back, and you pay it back into your own RRSP: You always pay income tax at your marginal rate on your RRSP withdrawals.** * Above, I said a precise meaning for \"\"retirement\"\" with respect to RRSPs is largely irrelevant. Yet, there are ages that matter: By the end of the year in which you turn 71, you are required to convert your RRSP to a RRIF. It's similar, but you can no longer contribute, and you must withdraw a minimum amount each year. Other circumstances related to age may qualify for minor tax relief intended for retirees, such as the Age Amount or the Pension Income Credit. Generally, such measures don't significantly change the fact that you pay income tax on RRSP withdrawals at your marginal rate – these measures raise the minimum you can take out without attracting tax, but most do nothing at the margin.** ** Exception: One might split eligible pension income with a spouse or common-law partner, which may reduce tax at the margin.\"",
"title": ""
},
{
"docid": "51086",
"text": "\"The primary tax-sheltered investing vehicles in Canada include: The RRSP. You can contribute up to 18% of your prior year's earned income, up to a limit ($24,930 in 2015, plus past unused contribution allowance) and receive an income tax deduction for your contributions. In an RRSP, investments grow on a tax-deferred basis. No tax is due until you begin withdrawals. When you withdraw funds, the withdrawn amount will be taxed at marginal income tax rates in effect at that time. The RRSP is similar to the U.S. \"\"traditional\"\" IRA, being an individual account with pre-tax contributions, tax-deferred growth, and ordinary tax rates applied to withdrawals. Yet, RRSPs have contribution limits higher than IRAs; higher, even, than U.S. 401(k) employee contribution limits. But, the RRSP is dissimilar to the IRA and 401(k) since an individual's annual contribution allowance isn't use-it-or-lose-it—unused allowance accumulates. The TFSA. Once you turn 18, you can put in up to $5,500 each year, irrespective of earned income. Like the RRSP, contribution room accumulates. If you were 18 in 2009 (when TFSAs were introduced) you'd be able to contribute $36,500 if you'd never contributed to one before. Unlike the RRSP, contributions to a TFSA are made on an after-tax basis and you pay no tax when you withdraw money. The post-tax nature of the TFSA and completely tax-free withdrawals makes them comparable to Roth-type accounts in the U.S.; i.e. while you won't get a tax deduction for contributing, you won't pay tax on earnings when withdrawn. Yet, unlike U.S. Roth-type accounts, you are not required to use the TFSA strictly for retirement savings—there is no penalty for pre-retirement withdrawal of TFSA funds. There are also employer-sponsored defined benefit (DB) and defined contribution (DC) retirement pension plans. Generally, employees who participate in these kinds of plans have their annual RRSP contribution limits reduced. I won't comment on these kinds of plans other than to say they exist and if your employer has one, check it out—many employees lose out on free money by not participating. The under-appreciated RESP. Typically used for education savings. A lifetime $50,000 contribution limit per beneficiary, and you can put that all in at once if you're not concerned about maximizing grants (see below). No tax deduction for contributions, but investments grow on a tax-deferred basis. Original contributions can be withdrawn tax-free. Qualified educational withdrawals of earnings are taxed as regular income in the hands of the beneficiary. An RESP beneficiary is typically a child, and in a child's case the Canadian federal government provides matching grant money (called CESG) of 20% on the first $2500 contributed each year, up to age 18, to a lifetime maximum of $7200 per beneficiary. Grant money is subject to additional conditions for withdrawal. While RESPs are typically used to save for a child's future education, there's nothing stopping an adult from opening an RESP for himself. If you've never had one, you can deposit $50,000 of after-tax money to grow on a tax-deferred basis for up to 36 years ... as far as I understand. An adult RESP will not qualify for CESG. Moreover, if you use the RESP strictly as a tax shelter and don't make qualified educational withdrawals when the time comes, your original contributions still come out free of tax but you'll pay ordinary income tax plus 20% additional tax on the earnings portion. That's the \"\"catch\"\"*. *However, if at that time you have accumulated sufficient RRSP contribution room, you may move up to $50,000 of your RESP earnings into your RRSP without any tax consequences (i.e. also avoiding the 20% additional tax) at time of transfer. Perhaps there's something above you haven't considered. Still, be sure to do your own due diligence and to consult a qualified, experienced, and conflict-free financial advisor for advice particular to your own situation.\"",
"title": ""
},
{
"docid": "451301",
"text": "\"From Wikipedia - Stock: The stock (also capital stock) of a corporation constitutes the equity stake of its owners. It represents the residual assets of the company that would be due to stockholders after discharge of all senior claims such as secured and unsecured debt. Stockholders' equity cannot be withdrawn from the company in a way that is intended to be detrimental to the company's creditors Wikipedia - Dividend: A dividend is a payment made by a corporation to its shareholders, usually as a distribution of profits. When a corporation earns a profit or surplus, it can re-invest it in the business (called retained earnings), and pay a fraction of this reinvestment as a dividend to shareholders. Distribution to shareholders can be in cash (usually a deposit into a bank account) or, if the corporation has a dividend reinvestment plan, the amount can be paid by the issue of further shares or share repurchase. Wikipedia - Bond: In finance, a bond is an instrument of indebtedness of the bond issuer to the holders. It is a debt security, under which the issuer owes the holders a debt and, depending on the terms of the bond, is obliged to pay them interest (the coupon) and/or to repay the principal at a later date, termed the maturity date. Interest is usually payable at fixed intervals (semiannual, annual, sometimes monthly). Very often the bond is negotiable, i.e. the ownership of the instrument can be transferred in the secondary market. This means that once the transfer agents at the bank medallion stamp the bond, it is highly liquid on the second market. Thus, stock is about ownership in the company, dividends are the payments those owners receive, which may be additional shares or cash usually, and bonds are about lending money. Stocks are usually bought through brokers on various stock exchanges generally. An exception can be made under \"\"Employee Stock Purchase Plans\"\" and other special cases where an employee may be given stock or options that allow the purchase of shares in the company through various plans. This would apply for Canada and the US where I have experience just as a parting note. This is without getting into Convertible Bond that also exists: In finance, a convertible bond or convertible note or convertible debt (or a convertible debenture if it has a maturity of greater than 10 years) is a type of bond that the holder can convert into a specified number of shares of common stock in the issuing company or cash of equal value. It is a hybrid security with debt- and equity-like features. It originated in the mid-19th century, and was used by early speculators such as Jacob Little and Daniel Drew to counter market cornering. Convertible bonds are most often issued by companies with a low credit rating and high growth potential.\"",
"title": ""
},
{
"docid": "27671",
"text": "\"For an RRSP, you do not have to pay taxes on money or investments until you withdraw the money. If you do not reinvest the dividends but instead, take them out as cash, that would be withdrawing the money. For mutual funds, you would normally reinvest the dividends if holding the investment inside an RRSP. For stocks, I believe the dividends would end up sitting in the cash part of your RRSP account (and you'd probably use the money to buy more stocks, though would not be required to do so). Either way, you do not pay tax on this investment income unless you withdraw it from your RRSP. For example, you invest $10,000 inside your RRSP. You get the tax benefit from doing so. You get dividends of $1,000 (hey, it was a good year), and use these to buy more stock. As the money never left your RRSP account, you are considered to have invested only your initial $10,000. If instead, you withdraw the $1,000 in dividends, you are taxed on $1000 income. TFSA are slightly more complicated. You don't get a tax benefit from your initial contribution, but then do not pay tax when you withdraw from the TFSA. Your investment income is still tax-free, and you are (generally) much more limited in how much you can contribute. For example, you invest $10,000 inside your TFSA. You get dividends of $1,000, and use these to buy more stock. Your total contributions to your TFSA remains at $10,000 as the money never left your account. You could instead withdraw the $1000 from your TFSA and would not pay tax on it. In the next calendar year (or later) after the withdrawal, you could \"\"repay\"\" the $1000 you took out without suffering an overcontribution penalty. This makes TFSA an excellent place to park emergency funds, as you can withdraw and subsequently replace the investment while continuing to get the tax benefits on your investment income. RRSPs are better for retirement or for the home buyers plan. In general, you should not be withdrawing money from either your TFSA or RRSP, except in emergencies, when retiring, or when purchasing a home. I prefer indexed mutual funds or money market accounts for both my RRSP and TFSA rather than individual stocks, but that's up to you.\"",
"title": ""
},
{
"docid": "307832",
"text": "I don't believe from reading the responses above that Questrade is doing anything 'original' or 'different' much less 'bad'. In RRSPs you are not allowed to go into debt. So the costs of all trades must be covered. If there is not enough USD to pay the bill then enough CAD is converted to do so. What else would anyone expect? How margin accounts work depends on whether the broker sets up different accounts for different currencies. Some do, some don't. The whole point of using 'margin' is to buy securities when you don't have the cash to cover the cost. The result is a 'short' position in the cash. Short positions accrue interest expense which is added to the balance once a month. Every broker does this. If you buy a US stock in a USD account without the cash to cover it, you will end up with USD margin debt. If you buy US stock in an account that co-mingles both USD and CAD assets and cash, then there will be options during the trade asking if you want to settle in USD or CAD. If you settle in CAD then obviously the broker will convert the necessary CAD funds to pay for it. If you settle in US funds, but there is no USD cash in the account, then again, you have created a short position in USD.",
"title": ""
},
{
"docid": "312811",
"text": "\"Share sales & purchases are accounted only on the balance sheet & cash flow statement although their effects are seen on the income statement. Remember, the balance sheet is like a snapshot in time of all accrued accounts; it's like looking at a glass of water and noting the level. The cash flow and income statements are like looking at the amount of water, \"\"actually\"\" and \"\"imaginary\"\" respectively, pumped in and out of the glass. So, when a corporation starts, it sells shares to whomever. The amount of cash received is accounted for in the investing section of the cash flow statement under the subheading \"\"issuance (retirement) of stock\"\" or the like, so when shares are sold, it is \"\"issuance\"\"; when a company buys back their shares, it's called \"\"retirement\"\", as cash inflows and outflows respectively. If you had a balance sheet before the shares were sold, you'd see under the \"\"equity\"\" heading a subheading common stock with a nominal (irrelevant) par value (this is usually something obnoxiously low like $0.01 per share used for ease of counting the shares from the Dollar amount in the account) under the subaccount almost always called \"\"common stock\"\". If you looked at the balance sheet after the sale, you'd see the number of shares in a note to the side. When shares trade publicly, the corporation usually has very little to do with it unless if they are selling or buying new shares under whatever label such as IPO, secondary offering, share repurchase, etc, but the corporation's volume from such activity would still be far below the activity of the third parties: shares are trading almost exclusively between third parties. These share sales and purchases will only be seen on the income statement under earnings per share (EPS), as EPS will rise and fall with stock repurchases and sales assuming income is held constant. While not technically part of the income statement but printed with it, the \"\"basic weighted average\"\" and \"\"diluted weighted average\"\" number of shares are also printed which are the weighted average over the reporting period of shares actually issued and expected if all promises to issue shares with employee stock options, grants, convertibles were made kept. The income statement is the accrual accounts of the operations of the company. It has little detail on investing (depreciation & appreciation) or financing (interest expenses & preferred dividends).\"",
"title": ""
},
{
"docid": "304085",
"text": "Any time there is a share adjustment from spin-off, merger, stock split, or reverse slit; there is zero chance for the stockholders to hang on to fractional shares. They are turned into cash. For the employees in the 401K program or investors via a mutual fund or ETF this isn't a problem. Because the fraction of a share left over is compared to the thousands or millions of shares owned by the fund as a collective. For the individual investor in the company this can be a problem that they aren't happy about. In some cases the fractional share is a byproduct that will result from any of these events. In the case of a corporate merger or spin-off most investors will not have an integer number of shares, so that fraction leftover that gets converted to cash isn't a big deal. When they want to boost the price to a specific range to meet a regulatory requirement, they are getting desperate and don't care that some will be forced out. In other cases it is by design to force many shareholders out. They want to go private. They to 1-for-1000 split. If you had less than 1000 shares pre-split then you will end up with zero shares plus cash. They know exactly what number to use. The result after the split is that the number of investors is small enough they they can now fall under a different set of regulations. They have gone dark, they don't have to file as many reports, and they can keep control of the company. Once the Board of Directors or the majority stockholders votes on this, the small investors have no choice.",
"title": ""
},
{
"docid": "433069",
"text": "I personally spoke with a Questrade agent about my question. To make a long story short: in a margin account, you are automatically issued a loan when buying U.S. stock with a Canadian money. Whereas, in a registered account (e.g. RRSP), the amount is converted on your behalf to cover the debit balance. Me: What happens if I open an account and I place an order for U.S. stocks with Canadian money? Is the amount converted at the time of transfer? How does that work? Agent: In a margin account, you are automatically issued a loan for a currency you do not have, however, if you have enough buying power, it will go through. The interest on the overnight balance is calculated daily and is charged on a monthly basis. We do not convert funds automatically in a margin account because you can have a debit cash balance. Agent: In a registered account, the Canada Revenue Agency does not allow a debit balance and therefore, we must convert your funds on your behalf to cover the debit balance if possible. We convert automatically overnight for a registered account. Agent: For example, if you buy U.S. equity you will need USD to buy it, and if you only have CAD, we will loan you USD to cover for that transaction. For example, if you had only $100 CAD and then wanted to buy U.S. stock worth $100 USD, then we will loan you $100 USD to purchase the stock. In a margin account we will not convert the funds automatically. Therefore, you will remain to have a $100 CAD credit and a $100 USD debit balance (or a loan) in your account. Me: I see, it means the longer I keep the stock, the higher interest will be? Agent: Well, yes, however, in a registered account there will be not be any interest since we convert your funds, but in a margin account, there will be interest until the debit balance is covered, or you can manually convert your funds by contacting us.",
"title": ""
},
{
"docid": "177648",
"text": "Your first scenario, involving shareholders in a private corp being limited by a contractual agreement, is common in practice. Frequent clauses include methods of valuing the shares if someone wants to sell, first right of refusal [you have to attempt to sell to the other shareholders, before you can sell to a 3rd party], and many others. These clauses are governed by contract law [ie: some clauses may be illegal in contract law, and therefore couldn't be applied here]. A Universal Shareholders' Agreement is just the same as the above, but applied to more people. You would never get an already public company to convert to a universal shareholders' agreement - because even 1 share voting 'no' would block it [due to corporate law limiting the power of a corporation from abusing minority shareholder value]. In practice, these agreements universally exist at the start of incorporation, or at least at the first moment shares become available. An example is the Canadian mega-construction company PCL*, which is employee-owned. When the original owner transferred the corporation to his employees, there was a USA in place which still today governs how the corporation operates. In theory you could have a 'public company' where most shares are already owned by the founders, and 100% of remaining shares are owned by a specific group of individuals, in which case you may be able to get a USA signed. But it wouldn't really happen in practice. *[Note that while PCL is broadly owned by a large group of employees, it is not a 'public company' because any random schmuck can't simply buy a share on the Toronto Stock Exchange. I assume most exchanges would prevent corporations from being listed if they had ownership restrictions like this].",
"title": ""
},
{
"docid": "213767",
"text": "\"The first 3 are the same as owning stock in a company would be measured in shares and would constitute some percentage of the overall shares outstanding. If there are 100 shares in the company in total, then owning 80 shares is owning 80% is the same as owning 80% of the common stock. This would be the typical ownership case though there can also be \"\"Restricted stock\"\" as something to note here. Convertible debt would likely carry interest charges as well as the choice at the end of becoming stock in the company. In this case, until the conversion is done, the stock isn't issued and thus isn't counted. Taking the above example, one could have a note that could be worth 10 shares but until the conversion is done, the debt is still debt. Some convertible debt could carry options or warrants for the underlying stock as there was the Berkshire convertible notes years ago that carried a negative interest rate that was studied in \"\"The Negative Coupon Bond\"\" if you want an example here. Options would have the right but not the obligation to buy the stock where there are \"\"Incentive Stock Options\"\" to research this in more depth. In this case, one could choose to not exercise the option and thus no stock changes hands. This is where some companies will experience dilution of ownership as employees and management may be given options that put more shares out to the public. Issuing debt wouldn't change the ownership and isn't direct ownership unless the company goes through a restructuring where the creditors become the new stock holders in the case of a Chapter 11 situation in the US. Note that this isn't really investing in a small business as much as it is making a loan to the company that will be paid back in cash. If the company runs into problems then the creditor could try to pursue the assets of the company to be repaid.\"",
"title": ""
},
{
"docid": "19433",
"text": "I believe your question is based on a false premise. First, no broker, that I know of, provides an RRSP account that is a margin account. RRSP accounts follow cash settlement rules. If you don't have the cash available, you can't buy a stock. You can't borrow money from your broker within your RRSP. If you want to borrow money to invest in your RRSP, you must borrow outside from another source, and make a contribution to your RRSP. And, if you do this, the loan interest is not considered tax deductible. In order for investment loan interest to be tax deductible, you'd need to invest outside of a registered type of account, e.g. using a regular non-tax-sheltered account. Even then, what you can deduct may be limited. Refer to CRA - Line 221 - Carrying charges and interest expenses: You can claim the following carrying charges and interest [...] [...] You cannot deduct on line 221 any of the following amounts:",
"title": ""
},
{
"docid": "161201",
"text": "Your assumption that funds sold in GBP trade in GBP is incorrect. In general funds purchase their constituent stocks in the fund currency which may be different to the subscription currency. Where the subscription currency is different from the fund currency subscriptions are converted into the fund currency before the extra money is used to increase holdings. An ETF, on the other hand, does not take subscriptions directly but by creation (and redemption) of shares. The principle is the same however; monies received from creation of ETF shares are converted into the fund currency and then used to buy stock. This ensures that only one currency transaction is done. In your specific example the fund currency will be USD so your purchase of the shares (assuming there are no sellers and creation occurs) will be converted from GBP to USD and held in that currency in the fund. The fund then trades entirely in USD to avoid currency risk. When you want to sell your exposure (supposing redemption occurs) enough holdings required to redeem your money are sold to get cash in USD and then converted to GBP before paying you. This means that trading activity where there is no need to convert to GBP (or any other currency) does not incur currency conversion costs. In practice funds will always have some cash (or cash equivalents) on hand to pay out redemptions and will have an idea of the number and size of redemptions each calendar period so will use futures and swaps to mitigate FX risk. Where the same firm has two funds traded in different currencies with the same objectives it is likely that one is a wrapper for the other such that one simply converts the currency and buys the other currency denominated ETF. As these are exchange traded funds with a price in GBP the amount you pay for the ETF or gain on selling it is the price given and you will not have to consider currency exchange as that should be done internally as explained above. However, there can be a (temporary) arbitrage opportunity if the price in GBP does not reflect the price in USD and the exchange rate put together.",
"title": ""
},
{
"docid": "589127",
"text": "\"There are more than a few different ways to consider why someone may have a transaction in the stock market: Employee stock options - If part of my compensation comes from having options that vest over time, I may well sell shares at various points because I don't want so much of my new worth tied up in one company stock. Thus, some transactions may happen from people cashing out stock options. Shorting stocks - This is where one would sell borrowed stock that then gets replaced later. Thus, one could reverse the traditional buy and sell order in which case the buy is done to close the position rather than open one. Convertible debt - Some companies may have debt that come with warrants or options that allow the holder to acquire shares at a specific price. This would be similar to 1 in some ways though the holder may be a mutual fund or company in some cases. There is also some people that may seek high-yield stocks and want an income stream from the stock while others may just want capital appreciation and like stocks that may not pay dividends(Berkshire Hathaway being the classic example here). Others may be traders believing the stock will move one way or another in the short-term and want to profit from that. So, thus the stock market isn't necessarily as simple as you state initially. A terrorist attack may impact stocks in a couple ways to consider: Liquidity - In the case of the attacks of 9/11, the stock market was closed for a number of days which meant people couldn't trade to convert shares to cash or cash to shares. Thus, some people may pull out of the market out of fear of their money being \"\"locked up\"\" when they need to access it. If someone is retired and expects to get $x/quarter from their stocks and it appears that that may be in jeopardy, it could cause one to shift their asset allocation. Future profits - Some companies may have costs to rebuild offices and other losses that could put a temporary dent in profits. If there is a company that makes widgets and the factory is attacked, the company may have to stop making widgets for a while which would impact earnings, no? There can also be the perception that an attack is \"\"just the beginning\"\" and one could extrapolate out more attacks that may affect broader areas. Sometimes what recently happens with the stock market is expected to continue that can be dangerous as some people may believe the market has to continue like the recent past as that is how they think the future will be.\"",
"title": ""
},
{
"docid": "525390",
"text": "\"A company has 100,000 shares and 100,000 unexercised call options (company issued). Share price and strike price both at $1. What country is this related to? I ask because, in the US, most people I know associate a \"\"call\"\" option with the instrument that is equivalent to 100 shares. So 100,000 calls would be 10,000,000 shares, which exceeds the number of shares you're saying the company has. I don't know if that means you pulled the numbers out of thin air, or whether it means you're thinking of a different type of option? Perhaps you meant incentive stock options meant to be given to employees? Each one of those is equivalent to a single share. They just aren't called \"\"call options\"\". In the rest of my answer, I'm going to assume you meant stock options. I assume the fact that these options exist will slow any price increases on the underlying shares due to potential dilution? I don't think the company can just create stock options without creating the underlying shares in the first place. Said another way, a more likely scenario is that company creates 200,000 shares and agrees to float 50% of them while reserving the other 50% as the pool for incentive employee stock. They then choose to give the employees options on the stock in the incentive pool, rather than outright grants of the stock, for various reasons. (One of which is being nice to the employees in regards to taxes since there is no US tax due at grant time if the strike price is the current price of the underlying stock.) An alternative scenario when the company shares are liquidly traded is that the company simply plans to buy back shares from the market in order to give employees their shares when options are exercised. In this case, the company needs the cash on hand, or cash flow to take money from, to buy those shares at current prices. Anyway, in either case, there is no dilution happening WHEN the options get exercised. Any dilution happened before or at the time the options were created. Meaning, the total number of shares in the company was already pre-set at an earlier time. As a result, the fact that the options exist in themselves will not slow price changes on the stock. However, price changes will be impacted by the total float of shares in the company, or the impact to cash flow if the company has to buy shares to redeem its option commitments. This is almost the same thing you're asking about, but it is technically different as to timing. If this is the case, can this be factored into any option pricing models like black-scholes? You're including the effect just by considering the total float of shares and net profits from cash flow when doing your modelling.\"",
"title": ""
},
{
"docid": "76530",
"text": "\"All transactions within an IRA are irrelevant as far as the taxation of the distributions from the IRA are concerned. You can only take cash from an IRA, and a (cash) distribution from a Traditional IRA is taxable as ordinary income (same as interest from a bank, say) without the advantage of any of the special tax rates for long-term capital gains or qualified dividends even if that cash was generated within the IRA from sales of stock etc. In short, just as with what is alleged to occur with respect to Las Vegas, what happens within the IRA stays within the IRA. Note: some IRA custodians are willing to make a distribution of stock or mutual fund shares to you, so that ownership of the 100 shares of GE, say, that you hold within your IRA is transferred to you in your personal (non-IRA) brokerage account. But, as far as the IRS is concerned, your IRA custodian sold the stock as the closing price on the day of the distribution, gave you the cash, and you promptly bought the 100 shares (at the closing price) in your personal brokerage account with the cash that you received from the IRA. It is just that your custodian saved the transaction fees involved in selling 100 shares of GE stock inside the IRA and you saved the transaction fee for buying 100 shares of GE stock in your personal brokerage account. Your basis in the 100 shares of GE stock is the \"\"cash_ that you imputedly received as a distribution from the IRA, so that when you sell the shares at some future time, your capital gains (or losses) will be with respect to this basis. The capital gains that occurred within the IRA when the shares were imputedly sold by your IRA custodian remain within the IRA, and you don't get to pay taxes on that at capital gains rates. That being said, I would like to add to what NathanL told you in his answer. Your mother passed away in 2011 and you are now 60 years old (so 54 or 55 in 2011?). It is likely that your mother was over 70.5 years old when she passed away, and so she likely had started taking Required Minimum Distributions from her IRA before her death. So, You should have been taking RMDs from the Inherited IRA starting with Year 2012. (The RMD for 2011, if not taken already by your mother before she passed away, should have been taken by her estate, and distributed to her heirs in accordance with her will, or, if she died intestate, in accordance with state law and/or probate court directives). There would not have been any 10% penalty tax due on the RMDs taken by you on the grounds that you were not 59.5 years old as yet; that rule applies to owners (your mom in this case) and not to beneficiaries (you in this case). So, have you taken the RMDs for 2012-2016? Or were you waiting to turn 59.5 before taking distributions in the mistaken belief that you would have to pay a 10% penalty for early wthdrawal? The penalty for not taking a RMD is 50% of the amount not distributed; yes, 50%. If you didn't take RMDs from the Inherited IRA for years 2012-2016, I recommend that you consult a CPA with expertise in tax law. Ask the CPA if he/she is an Enrolled Agent with the IRS: Enrolled Agents have to pass an exam administered by the IRS to show that they really understand tax law and are not just blowing smoke, and can represent you in front of the IRS in cases of audit etc,\"",
"title": ""
},
{
"docid": "212783",
"text": "\"Federal taxes are generally lower in Canada. Canada's top federal income tax rate is 29%; the US rate is 35% and will go to 39.6% when Bush tax cuts expire. The healthcare surcharge will kick in in a few years, pushing the top bracket by a few more points and over 40%. State/provincial taxes are lower in the US. You may end up in the 12% bracket in New York City or around 10% in California or other \"\"bad\"\" income-tax states. But Alberta is considered a tax haven in Canada and has a 10% flat tax. Ontario's top rate is about 11%, but there are surtaxes that can push the effective rate to about 17%. Investment income taxes: Canada wins, narrowly. Income from capital gains counts as half, so if you're very rich and live in Ontario, your rate is about 23% and less than that in Alberta. The only way to match or beat this deal in the US in the long term is to live in a no-income-tax state. Dividends are taxed at rates somewhere between capital gains and ordinary income - not as good a deal as Bush's 15% rate on preferred dividends, but that 15% rate will probably expire soon. Sales taxes: US wins, but the gap is closing. Canada has a national VAT-like tax, called GST and its rate came down from 7% to 5% when Harper became the Prime Minister. Provinces have sales taxes on top of that, in the range of 7-8% (but Alberta has no sales tax). Some provinces \"\"harmonized\"\" their sales taxes with the GST and charge a single rate, e.g. Ontario has a harmonized sales tax (HST) of 13% (5+8). 13% is of course a worse rate than the 6-8% charged by most states, but then some states and counties already charge 10% and the rates have been going up in each recession. Payroll taxes: much lower in Canada. Canadian employees' CPP and EI deductions have a low threshold and top out at about $3,000. Americans' 7.65% FICA rate applies to even $100K, resulting in a tax of $7,650. Property taxes: too dependent on the location, hard to tell. Tax benefits for retirement savings: Canada. If you work in the US and don't have a 401(k), you get a really bad deal: your retirement is underfunded and you're stuck with a higher tax bill, because you can't get the deduction. In Canada, if you don't have an RRSP at work, you take the money to the financial company of your choice, invest it there, and take the deduction on your taxes. If you don't like the investment options in your 401(k), you're stuck with them. If you don't like them in your RRSP, contribute the minimum to get the match and put the rest of the money into your individual RRSP; you still get the same deduction. Annual 401(k) contribution limits are use-it-or-lose-it, while unused RRSP limits and deductions can be carried forward and used when you need to jump tax brackets. Canada used to lack an answer to Roth IRAs, but the introduction of TFSAs took care of that. Mortgage interest deduction: US wins here as mortgage interest is not deductible in Canada. Marriage penalty: US wins. Canadian tax returns are of single or married-filing-separately type. So if you have one working spouse in the family or a big disparity between spouses' incomes, you can save money by filing a joint return. But such option is not available in Canada (there are ways to transfer some income between spouses and fund spousal retirement accounts, but if the income disparity is big, that won't be enough). Higher education: cheaper in Canada. This is not a tax item, but it's a big expense for many families and something the government can do about with your tax dollars. To sum it up, you may face higher or lower or about the same taxes after moving from US to Canada, depending on your circumstances. Another message here is that the high-tax, socialist, investment-unfriendly Canada is mostly a convenient myth.\"",
"title": ""
},
{
"docid": "442741",
"text": "You don't seem to have any particular question to be answered. Your understanding of RRSPs seems to be very good. Have you considered whether you might be better off putting your retirement savings into a TFSA instead? Both types can protect your growth from taxation (provided you reinvest the refund from the RRSP). The main way in which the RRSP is better than TFSA is that you can pay the tax on the contribution at a time when your income is lower, and thus have a lower marginal tax rate. Most people retire with a lower income than during their earning years, but it's a matter of tax brackets. If you think you'll be in the same bracket (same marginal tax rate) when you retire, then the TFSA and RRSP work out even in that regard. So in your case, the question you want to ask yourself is: when I retire, will I have an income (including CPP, OAS, pension payments, etc) that exceeds $45,282 worth of today's dollars? If so, your RRSP holds no advantage over the TFSA. In fact, the RRSP may even be worse, since the withdrawals count as income and reduce the amount of OAS and perhaps GIS payments that the government gives you - at least under current regulations. If you're unsure, I suggest you try this calculator from taxtips.ca that runs both scenarios and helps you see which one is more beneficial. It even factors in the OAS/GIS clawbacks.",
"title": ""
},
{
"docid": "12899",
"text": "Full disclosure: I’m an intern for EquityZen, so I’m familiar with this space but can speak with the most accuracy about EquityZen. Observations about other players in the space are my own. The employee liquidity landscape is evolving. EquityZen and Equidate help shareholders (employees, ex-employees, etc.) in private companies get liquidity for shares they already own. ESOFund and 137 Ventures help with option financing, and provide loans (and exotic structures on loans) to cover costs of exercising options and any associated tax hit. EquityZen is a private company marketplace that led the second wave of VC-backed secondary markets starting early 2013. The mission is to help achieve liquidity for employees and other private company shareholder, but in a company-approved way. EquityZen transacts with share transfers and also a proprietary derivative structure which transfers economics of a company's shares without changing voting and information rights. This structure typically makes the transfer process cheaper and faster as less paperwork is involved. Accredited investors find the process appealing because they get access to companies they usually cannot with small check sizes. To address the questions in Dzt's post: 1). EquityZen doesn't take a 'loan shark' approach meaning they don't front shareholders money so that they can purchase their stock. With EquityZen, you’re either selling your shares or selling all the economic risk—upside and downside—in exchange for today’s value. 2). EquityZen only allows company approved deals on the platform. As a result, companies are more friendly towards the process and they tend to allow these deals to take place. Non-company approved deals pose risks for buyers and sellers and are ultimately unsustainable. As a buyer, without company blessing, you’re taking on significant counterparty risk from the seller (will they make good on their promise to deliver shares in the future?) or the risk that the transfer is impermissible under relevant restrictions and your purchase is invalid. As a seller, you’re running the risk of violating your equity agreements, which can have severe penalties, like forfeiture of your stock. Your shares are also much less marketable when you’re looking to transact without the company’s knowledge or approval. 3). Terms don't change depending an a shareholder's situation. EquityZen is a professional company and values all of the shareholders that use the platform. It’s a marketplace so the market sets the price. In other situations, you may be at the mercy of just one large buyer. This can happen when you’re facing a big tax bill on exercise but don’t have the cash (because you have the stock). 4). EquityZen doesn't offer loans so this is a non issue. 5). Not EquityZen! EquityZen creates a clean break from the economics. It’s not uncommon for the loan structures to use an interest component as well as some other complications, like upside participation and and also a liquidation preference. EquityZen strives for a simple structure where you’re not on the hook for the downside and you’ve transferred all the upside as well.",
"title": ""
},
{
"docid": "331268",
"text": "The term self-directed generally refers to RRSP accounts where the account holder has not only the ability to determine a basic investment asset mix (such as can be accomplished even with a limited selection of mutual funds) but, more specifically, the self-directed account holder has a much wider choice of financial instruments beyond mutual funds, GICs, and/or cash savings. A self-directed RRSP generally permits the account holder to also invest or trade directly in financial instruments such as: Those kinds of instruments are not typically available in a non-self-directed mutual fund or bank RRSP. Typical mutual fund or bank RRSPs offer you only their choice of products – often with higher fees attached. Related resources:",
"title": ""
},
{
"docid": "17208",
"text": "See my comment for some discussion of why one might choose an identical fund over an ETF. As to why someone would choose the higher cost fund in this instance ... The Admiral Shares version of the fund (VFIAX) has the same expense ratio as the ETF but has a minimum investment of $10K. Some investors may want to eventually own the Admiral Shares fund but do not yet have $10K. If they begin with the Investor Shares now and then convert to Admiral later, that conversion will be a non-taxable event. If, however, they start with ETF shares now and then sell them later to buy the fund, that sale will be a taxable event. Vanguard ETFs are only commission-free to Vanguard clients using Vanguard Brokerage Services. Some investors using other brokers may face all sorts of penalties for purchasing third-party ETFs. Some retirement plan participants (either at Vanguard or another broker) may not even be allowed to purchase ETFs.",
"title": ""
},
{
"docid": "103842",
"text": "Does the 5 year rule apply on the After-tax 401k -> Roth 401k -> Roth IRA conversion of the 20000 (including 10000 earnings that was originally pre-tax)? No. The after-tax amounts are not subject to the 5 years rule. The earnings are. How does this affect Roth IRA withdrawal ordering rules with respect to the taxable portion of a single conversion being withdrawn before the non-taxable portion? Taxable portion first until exhausted. To better understand how it works, you need to understand the rationale behind the 5-year rule. Consider you have $100K in your IRA (traditional) and you want to take it out. Just withdrawing it would trigger a 10K statutory penalty, on top of the taxes due. But, you can use the backdoor Roth IRA, right? So convert the 100K, and then it becomes after-tax contribution to Roth IRA, and can be withdrawn with no penalty. One form filled ad 10K saved. To block this loophole, here comes the 5 years rule: you cannot withdraw after-tax amounts for at least 5 years without penalty, if the source was taxable conversion. Thus, in order to avoid the 10K penalty in the above situation, you have a 5-year cooling period, which makes the loophole useless for most cases. However amounts that are after tax can be withdrawn without penalty already, even from the traditional IRA, so there's no need in the 5 years cooling period. The withdrawal attribution is in this order: Roth IRA rollovers are sourced to the origin. E.g.: if you converted $100 to the Roth IRA at firm X and then a year later rolled it over to firm Y - it doesn't affect anything and the clock is ticking from the original date of the conversion at firm X. 5-year period applies to each conversion/rollover from a qualified retirement plan (see here). Distributions are applied to the conversions in FIFO order, so in one distribution, depending on the amounts, you may hit several different incoming conversions. The 5 years should be check on each of them, and the penalty applied on the amounts attributable to those that don't have enough time. 5-year period for contributions applies starting from the beginning of the first year of the first contribution that established your Roth IRA plan. The penalty applies to the amounts that were included in your gross income when conversion occurred, i.e.: doesn't apply on the amounts converted from after-tax sources. Note the difference from the traditional IRA - distributions from pre-tax sources are prorated between the non-deductible (basis) amounts and the deductible/earnings amounts (taxable). That is why the taxable amounts are first in the ordering of the distributions.",
"title": ""
},
{
"docid": "481169",
"text": "Firstly a stock split is easy, for example each unit of stock is converted into 10 units. So if you owned 1% of the company before the stock split, you will still own 1% after the stock split, but have 10 times the number of shares. The company does not pay out any money when doing this and there is no effect on tax for the company or the share holder. Now onto stock dividend… When a company make a profit, the company gives some of the profit to the share holders as a dividend; this is normally paid in cash. An investor may then wish to buy more shares in the company using the money from the dividend. However buying shares used to have a large cost in broker charges etc. Therefore some companies allowed share holders to choose to have the dividend paid as shares. The company buys enough of their own shares to cover the payout, only having one set of broker charges and then sends the correct number of shares to each share holder that has opted for a stock dividend. (Along with any cash that was not enough to buy a complete share.) This made since when you had paper shares and admin costs where high for stock brokers. It does not make sense these days. A stock dividend is taxed as if you had been paid the dividend in cash and then brought the stock yourself.",
"title": ""
},
{
"docid": "88539",
"text": "There are two significant drawbacks to this type of transfer. They were the reasons why I kept my American 401(k) as-is and started funding my Canadian RRSP from zero balance. 1. Taxes - a large chunk of your 401(k) will be lost to taxes. There is probably no way to transfer the funds without making a 401(k)/IRA withdrawal, which will incur the US federal tax and the 10% early-withdrawal penalty. When the money went into the 401(k), you got a tax deduction in the US and the tax break is supposed be repaid later when you make a withdrawal (that's basically how tax deferral works). It's unlikely that any country will let you take a deduction first and send the payback to a foreign country. The withdrawal amount may also be taxable in Canada (Canadians generally pay taxes on their global income and that includes pensions and distributions from foreign retirement plans). Foreign tax credit will apply of course, to eliminate double taxation, but it's of little help if your marginal Canadian tax rate is higher than your average US tax rate. 2. Expenses. Your RRSP will have to be invested in something and mutual fund management expenses are generally higher in Canada than in the US. For example, my employer-sponsored RRSP has a Standard & Poor's stock index fund that charges 1.5% and that is considered low-cost. It also offers a number of managed funds with expenses in excess of 2% that I simply ignore. You can probably invest your American 401(k)/IRA in mutual funds more efficiently.",
"title": ""
},
{
"docid": "394734",
"text": "Employees were already cashing out their RSUs and selling stock on private markets. >Even if Facebook could resist, an eager army of Facebook employees is pushing hard for an I.P.O., according to Eric Eldon of TechCrunch. In 2008, Facebook adopted a new restricted stock program that prevented employees from selling their shares until an I.P.O. or a sale, or if Facebook permitted it. They still could have stayed private if they really wanted to. They were compensating employees in stock, and those employees wanted to cash out. The underwriters wanted to cash out before the financials became open to public scrutiny.",
"title": ""
},
{
"docid": "152049",
"text": "\"I have some money invested on Merrill Edge. 2 days ago I purchased some mutual funds with most of the rest of my money in my account. I logged in today to see how it did, and noticed that there are 3 sections: Priced Investments, Cash & Money Accounts, and Pending Activity. In the Cash & Money section, there shows a negative balance of Cash (let's say -$1,000) and a positive \"\"Money Account Value\"\" (let's say +$1,100). The \"\"Money Account\"\" appears to be made up of $1 shares of something called \"\"ML Direct Deposit Program\"\". However, even though the mutual fund purchase was made 2 days ago, and the shares of the mutual funds are officially in my account, I'm still showing all of my \"\"Money Account\"\" shares ($1000). The balance sheet effectively makes it look like I somehow needed to have \"\"sold\"\" back my money account shares, converted them to cash, and then bought the funds. I'm hoping that isn't the case, and for some reason, there is a multiday lag between me buying stock and money getting deducted from my \"\"Money Account\"\". Hope that all makes sense. TLDR: what's the diff between a Cash account and Money Account that's filled with shares of \"\" ML Direct Deposit Program\"\"? Edit: Today the cash and money account offset by equal values equal to one of my mutual fund purchases.\"",
"title": ""
},
{
"docid": "312679",
"text": "Here's the best explanation I found relating to why your T4 box 39 might not have an amount filled in, even when box 38 has one: Department of Finance – Explanatory Notes Relating to the Income Tax Act [...]. It's a long document, but here's the part I believe relevant, with my emphasis: Employee Stock Options ITA 110(1) [...] Paragraph 110(1)(d) is amended to include a requirement that the employee [...] exercise the employee’s rights under the stock option agreement and acquire the securities underlying the agreement in order for the deduction in computing taxable income to be available [...] ensures that only one deduction is available in respect of an employment benefit. In other words, if employee stock option rights are surrendered to an employer for cash or an in-kind payment, then (subject to new subsections 110(1.1) and (1.2)) the employer may deduct the payment but the employee cannot claim the stock option deduction. Conversely, where an employer issues securities pursuant to an employee’s exercise of stock options, the employer can not deduct an amount in respect of the issuance, but the employee may be eligible to claim a deduction under paragraph 110(1)(d). Did you receive real shares based on your participation in the ESPP, or did you get a cash payment for the net value of shares you would have been issued under the plan? From what I can tell, if you opted for a cash payment (or if your plan only allows for such), then the part I emphasized comes into play. Essentially, if conditions were such that your employer could claim a deduction on their corporate income tax return for the compensation paid to you as part of the plan, then you are not also able to claim a similar deduction on your personal income tax return. The money received in that manner is effectively taxed in your hands the same as any bonus employment income would be; i.e. it isn't afforded tax treatment equivalent to capital gains income. Your employer and/or ESPP administrator are best able to confirm the conditions which led to no amount in your box 39, but at least based on above you can see there are legitimate cases where box 38 would have an amount while box 39 doesn't.",
"title": ""
},
{
"docid": "127958",
"text": "I think you are having trouble understanding what 'liquid' means. Liquidity refers to how easily an asset can be converted to cash. More liquid = more easily converted to cash, less liquid, less so. Any kind of exit load is going to make an asset less liquid due to the penalties associated with making the sale. So, the whole point of liquid funds is to give people the option of selling quickly if they need to. Since an exit load is meant to discourage this behavior, liquid funds tend not to have one. The point isn't what the financial institution 'gets', it's about offering a service to clients with a particular investment need.",
"title": ""
},
{
"docid": "444568",
"text": "There are some great answers on this site similar to what you asked, with either a non-jurisdictional or a US-centric focus. I would read those answers as well to give yourself more points of view on early investing. There are a few differences between Canada and the US from an investing perspective that you should also then consider, namely tax rules, healthcare, and education. I'll get Healthcare and Education out of the way quickly. Just note the difference in perspective in Canada of having government healthcare; putting money into health-savings plans or focusing on insurance as a workplace benefit is not a key motivating factor, but more a 'nice-to-have'. For education, it is more common in Canada for a student to either pay for school while working summer / part-time jobs, or at least taking on manageable levels of debt [because it is typically not quite as expensive as private colleges in the US]. There is still somewhat of a culture of saving for your child's education here, but it is not as much of a necessity as it may be in the US. From an investing perspective, I will quickly note some common [though not universal] general advice, before getting Canadian specific. I have blatantly stolen the meat of this section from Ben Miller's great answer here: Oversimplify it for me: the correct order of investing Once you have a solid financial footing, some peculiarities of Canadian investing are below. For all the tax-specific plans I'm about to mention, note that the banks do a very good job here of tricking you into believing they are complex, and that you need your hand to be held. I have gotten some criminally bad tax advice from banking reps, so at the risk of sounding prejudiced, I recommend that you learn everything you can beforehand, and only go into your bank when you already know the right answer. The 'account types' themselves just involve a few pages of paperwork to open, and the banks will often do that for free. They make up their fees in offering investment types that earn them management fees once the accounts are created. Be sure to separate the investments (stocks vs bonds etc.) vs the investment vehicles. Canada has 'Tax Free Savings Accounts', where you can contribute a certain amount of money every year, and invest in just about anything you want, from bonds to stocks to mutual funds. Any Income you earn in this account is completely tax free. You can withdraw these investments any time you want, but you can't re-contribute until January 1st of next year. ie: you invest $5k today in stocks held in a TFSA, and they grow to $6k. You withdraw $6k in July. No tax is involved. On January 1st next year, you can re-contribute a new $6K, and also any additional amounts added to your total limit annually. TFSA's are good for short-term liquid investments. If you don't know for sure when you'll need the money, putting it in a TFSA saves you some tax, but doesn't commit you to any specific plan of action. Registered Retirement Savings Plans allow you to contribute money based on your employment income accrued over your lifetime in Canada. The contributions are deducted from your taxable income in the year you make them. When you withdraw money from your RRSP, the amount you withdraw gets added as additional income in that year. ie: you invest $5k today in stocks held in an RRSP, and get a $5k deduction from your taxable income this year. The investments grow to $6k. You withdraw $6k next year. Your taxable income increases by $6k [note that if the investments were held 'normally' {outside of an RRSP}, you would have a taxable gain of only 50% of the total gain; but withdrawing the amount from your RRSP makes the gain 100% taxable]. On January 1st next year, you CANNOT recontribute this amount. Once withdrawn, it cannot be recontributed [except for below items]. RRSP's are good for long-term investing for retirement. There are a few factors at play here: (1) you get an immediate tax deduction, thus increasing the original size of investment by deferring tax to the withdrawal date; (2) your investments compound tax-free [you only pay tax at the end when you withdraw, not annually on earnings]; and (3) many people expect that they will have a lower tax-rate when they retire, than they do today. Some warnings about RRSP's: (1) They are less liquid than TFSA's; you can't put money in, take it out, and put it in again. In general, when you take it out, it's out, and therefore useless unless you leave it in for a long time; (2) Income gets re-characterized to be fully taxable [no dividend tax credits, no reduced capital gains tax rate]; and (3) There is no guarantee that your tax rate on retirement will be less than today. If you contribute only when your tax rate is in the top bracket, then this is a good bet, but even still, in 30 years, tax rates might rise by 20% [who knows?], meaning you could end up paying more tax on the back-end, than you saved in the short term. Home Buyer Plan RRSP withdrawals My single favourite piece of advice for young Canadians is this: if you contribute to an RRSP at least 3 months before you make a down payment on your first house, you can withdraw up to $25k from your RRSP without paying tax! to use for the down payment. Then over the next ~10 years, you need to recontribute money back to your RRSP, and you will ultimately be taxed when you finally take the money out at retirement. This means that contributing up to 25k to an RRSP can multiply your savings available for a down payment, by the amount of your tax rate. So if you make ~60k, you'll save ~35% on your 25k deposited, turning your down payment into $33,750. Getting immediate access to the tax savings while also having access to the cash for a downpayment, makes the Home Buyer Plan a solid way to make the most out of your RRSP, as long as one of your near-term goals is to own your own home. Registered Pension Plans are even less liquid than RRSPs. Tax-wise, they basically work the same: you get a deduction in the year you contribute, and are taxed when you withdraw. The big difference is that there are rules on when you are allowed to withdraw: only in retirement [barring specific circumstances]. Typically your employer's matching program (if you have one) will be inside of an RPP. Note that RPP's and RRSP's reduce your taxes on your employment paycheques immediately, if you contribute through a work program. That means you get the tax savings during the year, instead of all at once a year later on April 30th. *Note that I have attempted at all times to keep my advice current with applicable tax legislation, but I do not guarantee accuracy. Research these things yourself because I may have missed something relevant to your situation, I may be just plain wrong, and tax law may have changed since I wrote this to when you read it.",
"title": ""
},
{
"docid": "399932",
"text": "As a rule of thumb, no. Only in very rare circumstances will it prove better than a RRSP. The media has overplayed the usefulness of this account type for retirement savings. That's just a general rule. Your specific situation will make a difference but it's very easy to show that RRSPs will always outperform if the marginal rates are lower on withdrawal than when you deduct contributions from income. If you plan to use the money before retirement or you're expecting to collect GIS on retirement then you may need to look at the specifics of your situation. If you plan to put money in a RRSP and carry forward the deduction to use at a later date then it doesn't matter whether you put it in a RRSP now or use the TFSA and transfer it later. The RRSP also has advantages of some tax treaties and creditor protection. It (as a RRIF) can also be used after 65 for income splitting and the pension credit. An RESP can also provide a greater return as you get free money, which is always good. There are many other things you can do with it but I'd say it's always better in a TFSA than paying tax in a regular account. Since you pay the mortgage with after tax dollars that could be another option for the cash and it's a guaranteed return, albeit small nowadays.",
"title": ""
},
{
"docid": "68609",
"text": "\"I was told if I moved my 401k into a Roth IRA that school purposes is one reasons you can withdraw money without having to pay a tax. Incorrect. You will need to pay tax on the amount converted, since a 401(k) is pre-tax and a Roth IRA is after-tax. It will be added to your regular income, so you will pay tax at your marginal tax rate. is there any hidden tax or fee at all for withdrawing money from a Roth IRA for educational purposes? You still will need to pay the tax on the amount converted, but you'll avoid the 10% penalty for early withdrawal. I know that tuition, books and fees are covered for educational purposes. Can I take out of my Roth IRA for living expenses while I'm attending school? Rent, gas, food, etc... Room and board, yes, so long as you are half-time, but not gas/food Possibly only room and board for staying on-campus, but I'm not certain, although I doubt you could call your normal house payment \"\"education expense\"\" with my 401k being smaller, would it just be better to go ahead and cash the whole thing and just pay the tax and use it for whatever I need it for? What is the tax if I just decide to cash the whole thing in? You pay your marginal tax rate PLUS a 10% penalty for early withdrawal. So no, this is probably not a wise move financially unless you're on the verge of bankruptcy or foreclosure (where distress costs are much higher then the 10% penalty) I can't answer the other questions regarding grants; I would talk to the financial aid department at your school. Bottom line, transferring your 401(k) is very likely a bad idea unless you can afford to pay the tax in cash (meaning without borrowing). My advice would be to leave your 401(k) alone (it's meant for retirement not for school or living expenses) Ideally, you should pay for as much as you can out of cash flow, and don't take out more student loans. That may mean taking fewer classes, getting another part time job, finding a different (cheaper) school, applying for more grants and scholarships, etc. I would not in ANY circumstance cash out your 401(k) to pay for school. You'll be much worse off in the long run, and there are much cheaper ways to get money.\"",
"title": ""
}
] |
687
|
Lamins are found within the inner layer of the nuclear membrane of all cells.
|
[
{
"docid": "4452659",
"text": "Macroautophagy (hereafter referred to as autophagy) is a catabolic membrane trafficking process that degrades a variety of cellular constituents and is associated with human diseases. Although extensive studies have focused on autophagic turnover of cytoplasmic materials, little is known about the role of autophagy in degrading nuclear components. Here we report that the autophagy machinery mediates degradation of nuclear lamina components in mammals. The autophagy protein LC3/Atg8, which is involved in autophagy membrane trafficking and substrate delivery, is present in the nucleus and directly interacts with the nuclear lamina protein lamin B1, and binds to lamin-associated domains on chromatin. This LC3-lamin B1 interaction does not downregulate lamin B1 during starvation, but mediates its degradation upon oncogenic insults, such as by activated RAS. Lamin B1 degradation is achieved by nucleus-to-cytoplasm transport that delivers lamin B1 to the lysosome. Inhibiting autophagy or the LC3-lamin B1 interaction prevents activated RAS-induced lamin B1 loss and attenuates oncogene-induced senescence in primary human cells. Our study suggests that this new function of autophagy acts as a guarding mechanism protecting cells from tumorigenesis.",
"title": "Autophagy mediates degradation of nuclear lamina"
}
] |
[
{
"docid": "34747208",
"text": "Mutations in the nuclear structural protein lamin A cause the premature aging syndrome Hutchinson-Gilford progeria (HGPS). Whether lamin A plays any role in normal aging is unknown. We show that the same molecular mechanism responsible for HGPS is active in healthy cells. Cell nuclei from old individuals acquire defects similar to those of HGPS patient cells, including changes in histone modifications and increased DNA damage. Age-related nuclear defects are caused by sporadic use, in healthy individuals, of the same cryptic splice site in lamin A whose constitutive activation causes HGPS. Inhibition of this splice site reverses the nuclear defects associated with aging. These observations implicate lamin A in physiological aging.",
"title": "Lamin A-dependent nuclear defects in human aging."
},
{
"docid": "10518721",
"text": "Our eyes send different 'images' of the outside world to the brain — an image of contours (line drawing), a colour image (watercolour painting) or an image of moving objects (movie). This is commonly referred to as parallel processing, and starts as early as the first synapse of the retina, the cone pedicle. Here, the molecular composition of the transmitter receptors of the postsynaptic neurons defines which images are transferred to the inner retina. Within the second synaptic layer — the inner plexiform layer — circuits that involve complex inhibitory and excitatory interactions represent filters that select 'what the eye tells the brain'.",
"title": "Parallel processing in the mammalian retina"
},
{
"docid": "22544171",
"text": "Hutchinson-Gilford progeria syndrome (HGPS) is a childhood premature aging disease caused by a spontaneous point mutation in lamin A (encoded by LMNA), one of the major architectural elements of the mammalian cell nucleus. The HGPS mutation activates an aberrant cryptic splice site in LMNA pre-mRNA, leading to synthesis of a truncated lamin A protein and concomitant reduction in wild-type lamin A. Fibroblasts from individuals with HGPS have severe morphological abnormalities in nuclear envelope structure. Here we show that the cellular disease phenotype is reversible in cells from individuals with HGPS. Introduction of wild-type lamin A protein does not rescue the cellular disease symptoms. The mutant LMNA mRNA and lamin A protein can be efficiently eliminated by correction of the aberrant splicing event using a modified oligonucleotide targeted to the activated cryptic splice site. Upon splicing correction, HGPS fibroblasts assume normal nuclear morphology, the aberrant nuclear distribution and cellular levels of lamina-associated proteins are rescued, defects in heterochromatin-specific histone modifications are corrected and proper expression of several misregulated genes is reestablished. Our results establish proof of principle for the correction of the premature aging phenotype in individuals with HGPS.",
"title": "Reversal of the cellular phenotype in the premature aging disease Hutchinson-Gilford progeria syndrome"
},
{
"docid": "5914739",
"text": "The CD3ε and ζ cytoplasmic domains of the T cell receptor bind to the inner leaflet of the plasma membrane (PM), and a previous nuclear magnetic resonance structure showed that both tyrosines of the CD3ε immunoreceptor tyrosine-based activation motif partition into the bilayer. Electrostatic interactions between acidic phospholipids and clusters of basic CD3ε residues were previously shown to be essential for CD3ε and ζ membrane binding. Phosphatidylserine (PS) is the most abundant negatively charged lipid on the inner leaflet of the PM and makes a major contribution to membrane binding by the CD3ε cytoplasmic domain. Here, we show that TCR triggering by peptide--MHC complexes induces dissociation of the CD3ε cytoplasmic domain from the plasma membrane. Release of the CD3ε cytoplasmic domain from the membrane is accompanied by a substantial focal reduction in negative charge and available PS in TCR microclusters. These changes in the lipid composition of TCR microclusters even occur when TCR signaling is blocked with a Src kinase inhibitor. Local changes in the lipid composition of TCR microclusters thus render the CD3ε cytoplasmic domain accessible during early stages of T cell activation.",
"title": "Local changes in lipid environment of TCR microclusters regulate membrane binding by the CD3ε cytoplasmic domain"
},
{
"docid": "15692098",
"text": "Hutchinson-Gilford progeria syndrome (HGPS) is a rare but well known entity characterized by extreme short stature, low body weight, early loss of hair, lipodystrophy, scleroderma, decreased joint mobility, osteolysis, and facial features that resemble aged persons. Cardiovascular compromise leads to early demise. Cognitive development is normal. Data on 10 of our own cases and 132 cases from literature are presented. The incidence in the last century in the Netherlands was 1:4,000,000. Sex ratio was 1.2:1. Main first symptoms were failure to thrive (55%), hair loss (40%), skin problems (28%), and lipodystrophy (20%). Mean age at diagnosis was 2.9 years. Growth in weight was more disturbed than growth in height, and growth delay started already prenatally. Mean height > 13 years was 109.0 cm, mean weight was 14.5 kg. Osteolysis was wide-spread but not expressed, except in the viscerocranium, and remained limited to membranous formed bone. Lipodystrophy is generalized, only intra-abdominal fat depositions remain present. Cardiovascular problems are extremely variable, both in age of onset and nature. Stroke and coronary dysfunctioning are most frequent. Pathologic findings in coronaries and aorta resemble sometimes the findings in elderly persons, but can also be much more limited. Loss of smooth muscle cells seems the most important finding. Mean age of demise was 12.6 years. Patients can be subdivided in patients with classical HGPS, which follows an autosomal dominant pattern of inheritance, (almost) all cases representing spontaneous mutations, and in non-classical progeria, in whom growth can be less retarded, scalp hair remains present for a longer time, lipodystrophy is more slowly progressive, osteolysis is more expressed except in the face, and survival well into adulthood is not uncommon. Pattern of inheritance of non-classical progeria is most probably autosomal recessive. The cause of HGPS is an abnormally formed Lamin A, either directly by a mutated LMNA gene, or through abnormal posttranslational processing (ZMPSTE24 gene mutations). Of 34 LMNA mutations found in progeria patients, there were 26 classical p. G608G mutations (76%). Pathogenesis is most likely to follow several different pathways. Potential therapeutic strategies are developed along these lines and include RNA interference techniques and inhibition of the dominant-negative influence of abnormally formed Lamin A on polymerization with normally formed Lamin A.",
"title": "Hutchinson-Gilford progeria syndrome: review of the phenotype"
},
{
"docid": "7481159",
"text": "Gram-negative bacteria use the Type VI secretion system (T6SS) to inject toxic proteins into rival bacteria or eukaryotic cells. However, the mechanism of the T6SS is incompletely understood. In the present study, we investigated a conserved component of the T6SS, TssK, using the antibacterial T6SS of Serratia marcescens as a model system. TssK was confirmed to be essential for effector secretion by the T6SS. The native protein, although not an integral membrane protein, appeared to localize to the inner membrane, consistent with its presence within a membrane-anchored assembly. Recombinant TssK purified from S. marcescens was found to exist in several stable oligomeric forms, namely trimer, hexamer and higher-order species. Native-level purification of TssK identified TssF and TssG as interacting proteins. TssF and TssG, conserved T6SS components of unknown function, were required for T6SS activity, but not for correct localization of TssK. A complex containing TssK, TssF and TssG was subsequently purified in vitro, confirming that these three proteins form a new subcomplex within the T6SS. Our findings provide new insight into the T6SS assembly, allowing us to propose a model whereby TssK recruits TssFG into the membrane-associated T6SS complex and different oligomeric states of TssK may contribute to the dynamic mechanism of the system.",
"title": "Biochemical analysis of TssK, a core component of the bacterial Type VI secretion system, reveals distinct oligomeric states of TssK and identifies a TssK–TssFG subcomplex"
},
{
"docid": "37362689",
"text": "The bulk of ATP consumed by various cellular processes in higher eukaryotes is normally produced by five multimeric protein complexes (I-V) embedded within the inner mitochondrial membrane, in a process known as oxidative phosphorylation (OXPHOS). Maintenance of energy homeostasis under most physiological conditions is therefore contingent upon the ability of OXPHOS to meet cellular changes in bioenergetic demand, with a chronic failure to do so being a frequent cause of human disease. With the exception of Complex II, the structural subunits of OXPHOS complexes are encoded by both the nuclear and the mitochondrial genomes. The physical separation of the two genomes necessitates that the expression of the 13 mitochondrially encoded polypeptides be co-ordinated with that of relevant nuclear-encoded partners in order to assemble functional holoenzyme complexes. Complex biogenesis is a highly ordered process, and several nuclear-encoded factors that function at distinct stages in the assembly of individual OXPHOS complexes have been identified.",
"title": "Oxidative phosphorylation: synthesis of mitochondrially encoded proteins and assembly of individual structural subunits into functional holoenzyme complexes."
},
{
"docid": "4701662",
"text": "As phospholipids are synthesized mainly in the endoplasmic reticulum (ER) and mitochondrial inner membranes, how cells properly distribute specific phospholipids to diverse cellular membranes is a crucial problem for maintenance of organelle-specific phospholipid compositions. Although the ER-mitochondria encounter structure (ERMES) was proposed to facilitate phospholipid transfer between the ER and mitochondria, such a role of ERMES is still controversial and awaits experimental demonstration. Here we developed a novel in vitro assay system with isolated yeast membrane fractions to monitor phospholipid exchange between the ER and mitochondria. With this system, we found that phospholipid transport between the ER and mitochondria relies on membrane intactness, but not energy sources such as ATP, GTP or the membrane potential across the mitochondrial inner membrane. We further found that lack of the ERMES component impairs the phosphatidylserine transport from the ER to mitochondria, but not the phosphatidylethanolamine transport from mitochondria to the ER. This in vitro assay system thus offers a powerful tool to analyze the non-vesicular phospholipid transport between the ER and mitochondria.",
"title": "A phospholipid transfer function of ER-mitochondria encounter structure revealed in vitro"
},
{
"docid": "26374799",
"text": "Human embryonic stem cells (hESCs) self-renew indefinitely and give rise to derivatives of all three primary germ layers, yet little is known about the signaling cascades that govern their pluripotent character. Because it plays a prominent role in the early cell fate decisions of embryonic development, we have examined the role of TGFbeta superfamily signaling in hESCs. We found that, in undifferentiated cells, the TGFbeta/activin/nodal branch is activated (through the signal transducer SMAD2/3) while the BMP/GDF branch (SMAD1/5) is only active in isolated mitotic cells. Upon early differentiation, SMAD2/3 signaling is decreased while SMAD1/5 signaling is activated. We next tested the functional role of TGFbeta/activin/nodal signaling in hESCs and found that it is required for the maintenance of markers of the undifferentiated state. We extend these findings to show that SMAD2/3 activation is required downstream of WNT signaling, which we have previously shown to be sufficient to maintain the undifferentiated state of hESCs. Strikingly, we show that in ex vivo mouse blastocyst cultures, SMAD2/3 signaling is also required to maintain the inner cell mass (from which stem cells are derived). These data reveal a crucial role for TGFbeta signaling in the earliest stages of cell fate determination and demonstrate an interconnection between TGFbeta and WNT signaling in these contexts.",
"title": "TGFbeta/activin/nodal signaling is necessary for the maintenance of pluripotency in human embryonic stem cells."
},
{
"docid": "40094786",
"text": "Cytotoxic T lymphocytes (CTL) rapidly destroy their targets. Here we show that although target cell death occurs within 5 min of CTL-target cell contact, an immunological synapse similar to that seen in CD4 cells rapidly forms in CTL, with a ring of adhesion proteins surrounding an inner signaling molecule domain. Lytic granule secretion occurs in a separate domain within the adhesion ring, maintaining signaling protein organization during exocytosis. Live and fixed cell studies show target cell plasma membrane markers are transferred to the CTL as the cells separate. Electron microscopy reveals continuities forming membrane bridges between the CTL and target cell membranes, suggesting a possible mechanism for this transfer.",
"title": "The immunological synapse of CTL contains a secretory domain and membrane bridges."
},
{
"docid": "25036988",
"text": "Nuclear lamin B1 (LMNB1) constitutes one of the major structural proteins in the lamina mesh. We silenced the expression of LMNB1 by RNA interference in the colon cancer cell line DLD-1 and showed a dramatic redistribution of H3K27me3 from the periphery to a more homogeneous nuclear dispersion. In addition, we observed telomere attrition and an increased frequency of micronuclei and nuclear blebs. By 3D-FISH analyses, we demonstrated that the volume and surface of chromosome territories were significantly larger in LMNB1-depleted cells, suggesting that LMNB1 is required to maintain chromatin condensation in interphase nuclei. These changes led to a prolonged S phase due to activation of Chk1. Finally, silencing of LMNB1 resulted in extensive changes in alternative splicing of multiple genes and in a higher number of enlarged nuclear speckles. Taken together, our results suggest a mechanistic role of the nuclear lamina in the organization of chromosome territories, maintenance of genome integrity and proper gene splicing.",
"title": "Loss of lamin B1 results in prolongation of S phase and decondensation of chromosome territories."
},
{
"docid": "36651210",
"text": "Embryonic stem cells have the ability to remain undifferentiated and proliferate indefinitely in vitro while maintaining the potential to differentiate into derivatives of all three embryonic germ layers. These cells have, therefore, potential for in vitro differentiation studies, gene function, and so on. The aim of this study was to produce a human embryonic stem cell line. An inner cell mass of a human blastocyst was separated and cultured on mouse embryonic fibroblasts in embryonic stem cell medium with related additives. The established line was evaluated by morphology; passaging; freezing and thawing; alkaline phosphatase; Oct-4 expression; anti-surface markers including Tra-1-60 and Tra-1-81; and karyotype and spontaneous differentiation. Differentiated cardiomyocytes and neurons were evaluated by transmission electron microscopy and immunocytochemistry. Here, we report the derivation of a new embryonic stem cell line (Royan H1) from a human blastocyst that remains undifferentiated in morphology during continuous passaging for more than 30 passages, maintains a normal XX karyotype, is viable after freezing and thawing, and expresses alkaline phosphatase, Oct-4, Tra-1-60, and Tra-1-81. These cells remain undifferentiated when grown on mouse embryonic fibroblast feeder layers in the presence or absence of recombinant human leukemia inhibitory factor. Royan H1 cells can differentiate in vitro in the absence of feeder cells and can produce embryoid bodies that can further differentiate into beating cardiomyocytes as well as neurons. These results define Royan H1 cells as a new human embryonic stem cell line.",
"title": "Establishment and in vitro differentiation of a new embryonic stem cell line from human blastocyst."
},
{
"docid": "43054703",
"text": "Neutrophil extracellular traps (NETs) are webs of DNA covered with antimicrobial molecules that constitute a newly described killing mechanism in innate immune defense. Previous publications reported that NETs take up to 3-4 h to form via an oxidant-dependent event that requires lytic death of neutrophils. In this study, we describe neutrophils responding uniquely to Staphylococcus aureus via a novel process of NET formation that did not require neutrophil lysis or even breach of the plasma membrane. The multilobular nucleus rapidly became rounded and condensed. During this process, we observed the separation of the inner and outer nuclear membranes and budding of vesicles, and the separated membranes and vesicles were filled with nuclear DNA. The vesicles were extruded intact into the extracellular space where they ruptured, and the chromatin was released. This entire process occurred via a unique, very rapid (5-60 min), oxidant-independent mechanism. Mitochondrial DNA constituted very little if any of these NETs. They did have a limited amount of proteolytic activity and were able to kill S. aureus. With time, the nuclear envelope ruptured, and DNA filled the cytoplasm presumably for later lytic NET production, but this was distinct from the vesicular release mechanism. Panton-Valentine leukocidin, autolysin, and a lipase were identified in supernatants with NET-inducing activity, but Panton-Valentine leukocidin was the dominant NET inducer. We describe a new mechanism of NET release that is very rapid and contributes to trapping and killing of S. aureus.",
"title": "A novel mechanism of rapid nuclear neutrophil extracellular trap formation in response to Staphylococcus aureus."
},
{
"docid": "797114",
"text": "A recent study revealed a mechanism of delaying aging in yeast by a natural compound which specifically impacts mitochondrial redox processes. In this mechanism, exogenously added lithocholic bile acid enters yeast cells, accumulates mainly in the inner mitochondrial membrane, and elicits an age-related remodeling of phospholipid synthesis and movement within both mitochondrial membranes. Such remodeling of mitochondrial phospholipid dynamics progresses with the chronological age of a yeast cell and ultimately causes significant changes in mitochondrial membrane lipidome. These changes in the composition of membrane phospholipids alter mitochondrial abundance and morphology, thereby triggering changes in the age-related chronology of such longevity-defining redox processes as mitochondrial respiration, the maintenance of mitochondrial membrane potential, the preservation of cellular homeostasis of mitochondrially produced reactive oxygen species, and the coupling of electron transport to ATP synthesis.",
"title": "A mitochondrially targeted compound delays aging in yeast through a mechanism linking mitochondrial membrane lipid metabolism to mitochondrial redox biology☆"
},
{
"docid": "29641682",
"text": "Pluripotent cells arise within the inner cell mass (ICM) of mammals and have the potential to generate all cell types of the adult organism through a process of commitment and ordered differentiation. Despite many decades of investigation, the mechanisms that guide and stabilise cell fate choice as well as those that can be engineered to promote its reversal, remain only partially resolved. Reprogramming of somatic cells towards a pluripotent-like state can be achieved by several different experimental routes including nuclear transfer, the supply of a defined cocktail of transcription factors, or by fusing somatic cells with a pluripotent stem cell partner. These approaches have been used to demonstrate the remarkable intrinsic epigenetic plasticity of many terminally differentiated cell types, as well as to define the factors that are required for pluripotent conversion. In this review we summarise some recent advances using cell fusion-based studies to better understand the basis of pluripotency and the epigenetic mechanisms that promote cell type inter-conversion.",
"title": "Reprogramming somatic cells towards pluripotency by cellular fusion."
},
{
"docid": "3896759",
"text": "Blood and lymphatic vessels pervade almost all body tissues and have numerous essential roles in physiology and disease. The inner lining of these networks is formed by a single layer of endothelial cells, which is specialized according to the needs of the tissue that it supplies. Whereas the general mechanisms of blood and lymphatic vessel development are being defined with increasing molecular precision, studies of the processes of endothelial specialization remain mostly descriptive. Recent insights from genetic animal models illuminate how endothelial cells interact with each other and with their tissue environment, providing paradigms for vessel type- and organ-specific endothelial differentiation. Delineating these governing principles will be crucial for understanding how tissues develop and maintain, and how their function becomes abnormal in disease.",
"title": "Vascular heterogeneity and specialization in development and disease"
},
{
"docid": "4423327",
"text": "Nanog is a divergent homeodomain protein found in mammalian pluripotent cells and developing germ cells. Deletion of Nanog causes early embryonic lethality, whereas constitutive expression enables autonomous self-renewal of embryonic stem cells. Nanog is accordingly considered a core element of the pluripotent transcriptional network. However, here we report that Nanog fluctuates in mouse embryonic stem cells. Transient downregulation of Nanog appears to predispose cells towards differentiation but does not mark commitment. By genetic deletion we show that, although they are prone to differentiate, embryonic stem cells can self-renew indefinitely in the permanent absence of Nanog. Expanded Nanog null cells colonize embryonic germ layers and exhibit multilineage differentiation both in fetal and adult chimaeras. Although they are also recruited to the germ line, primordial germ cells lacking Nanog fail to mature on reaching the genital ridge. This defect is rescued by repair of the mutant allele. Thus Nanog is dispensible for expression of somatic pluripotency but is specifically required for formation of germ cells. Nanog therefore acts primarily in construction of inner cell mass and germ cell states rather than in the housekeeping machinery of pluripotency. We surmise that Nanog stabilizes embryonic stem cells in culture by resisting or reversing alternative gene expression states.",
"title": "Nanog safeguards pluripotency and mediates germline development"
},
{
"docid": "14446279",
"text": "In the yeast Saccharomyces cerevisiae that lacks lamins, the nuclear pore complex (NPC) has been proposed to serve a role in chromatin organization. Here, using fluorescence microscopy in living cells, we show that nuclear pore proteins of the Nup84 core complex, Nup84p, Nup145Cp, Nup120p, and Nup133p, serve to anchor telomere XI-L at the nuclear periphery. The integrity of this complex is shown to be required for repression of a URA3 gene inserted in the subtelomeric region of this chromosome end. Furthermore, altering the integrity of this complex decreases the efficiency of repair of a DNA double-strand break (DSB) only when it is generated in the subtelomeric region, even though the repair machinery is functional. These effects are specific to the Nup84 complex. Our observations thus confirm and extend the role played by the NPC, through the Nup84 complex, in the functional organization of chromatin. They also indicate that anchoring of telomeres is essential for efficient repair of DSBs occurring therein and is important for preserving genome integrity.",
"title": "Telomere tethering at the nuclear periphery is essential for efficient DNA double strand break repair in subtelomeric region"
},
{
"docid": "1769799",
"text": "Transformation and conjugation permit the passage of DNA through the bacterial membranes and represent dominant modes for the transfer of genetic information between bacterial cells or between bacterial and eukaryotic cells. As such, they are responsible for the spread of fitness-enhancing traits, including antibiotic resistance. Both processes usually involve the recognition of double-stranded DNA, followed by the transfer of single strands. Elaborate molecular machines are responsible for negotiating the passage of macromolecular DNA through the layers of the cell surface. All or nearly all the machine components involved in transformation and conjugation have been identified, and here we present models for their roles in DNA transport.",
"title": "The ins and outs of DNA transfer in bacteria."
},
{
"docid": "10546779",
"text": "Somatic cell nuclear transfer (SCNT) technology has recently been used to generate animals with a common genetic composition. In this study, we report the derivation of a pluripotent embryonic stem (ES) cell line (SCNT-hES-1) from a cloned human blastocyst. The SCNT-hES-1 cells displayed typical ES cell morphology and cell surface markers and were capable of differentiating into embryoid bodies in vitro and of forming teratomas in vivo containing cell derivatives from all three embryonic germ layers in severe combined immunodeficient mice. After continuous proliferation for more than 70 passages, SCNT-hES-1 cells maintained normal karyotypes and were genetically identical to the somatic nuclear donor cells. Although we cannot completely exclude the possibility that the cells had a parthenogenetic origin, imprinting analyses support a SCNT origin of the derived human ES cells.",
"title": "Evidence of a pluripotent human embryonic stem cell line derived from a cloned blastocyst."
},
{
"docid": "7643848",
"text": "We have characterized the membrane topology of a 60-kDa inner membrane protein from Escherichia coli that is homologous to the recently identified Oxa1p protein in Saccharomyces cerevisiae mitochondria implicated in the assembly of mitochondrial inner membrane proteins. Hydrophobicity and alkaline phosphatase fusion analyses suggest a membrane topology with six transmembrane segments, including an N-terminal signal-anchor sequence not present in mitochondrial Oxa1p. In contrast to partial N-terminal fusion protein constructs, the full-length protein folds into a protease-resistant conformation, suggesting that important folding determinants are present in the C-terminal part of the molecule.",
"title": "Membrane topology of the 60-kDa Oxa1p homologue from Escherichia coli."
},
{
"docid": "13411519",
"text": "Following cell surface receptor activation, the alpha subunit of the Gq subclass of GTP-binding proteins activates the phosphoinositide signalling pathway. Here we examined the expression and localization of Gq protein alpha subunits in the adult mouse brain by in situ hybridization and immunohistochemistry. Of the four members of the Gq protein alpha subunits, Galphaq and Galpha11 were transcribed predominantly in the brain. The highest transcriptional level of Galphaq was observed in cerebellar Purkinje cells (PCs) and hippocampal pyramidal cells, while that of Galpha11 was noted in hippocampal pyramidal cells. Antibody against the C-terminal peptide common to Galphaq and Galpha11 strongly labelled the cerebellar molecular layer and hippocampal neuropil layers. In these regions, immunogold preferentially labelled the cytoplasmic face of postsynaptic cell membrane of PCs and pyramidal cells. Immunoparticles were distributed along the extra-junctional cell membrane of spines, dendrites and somata, but were almost excluded from the junctional membrane. By double immunofluorescence, Galphaq/Galpha11 was extensively colocalized with metabotropic glutamate receptor mGluR1alpha in dendritic spines of PCs and with mGluR5 in those of hippocampal pyramidal cells. Together with concentrated localization of mGluR1alpha and mGluR5 in a peri-junctional annulus on PC and pyramidal cell synapses (Baude et al. 1993, Neuron, 11, 771-787; Luján et al. 1996, Eur. J. Neurosci., 8, 1488-1500), the present molecular-anatomical findings suggest that peri-junctional stimulation of the group I metabotropic glutamate receptors is mediated by Galphaq and/or Galpha11, leading to the activation of the intracellular effector, phospholipase Cbeta.",
"title": "Gq protein alpha subunits Galphaq and Galpha11 are localized at postsynaptic extra-junctional membrane of cerebellar Purkinje cells and hippocampal pyramidal cells."
},
{
"docid": "37608303",
"text": "Cristae, the organized invaginations of the mitochondrial inner membrane, respond structurally to the energetic demands of the cell. The mechanism by which these dynamic changes are regulated and the consequences thereof are largely unknown. Optic atrophy 1 (OPA1) is the mitochondrial GTPase responsible for inner membrane fusion and maintenance of cristae structure. Here, we report that OPA1 responds dynamically to changes in energetic conditions to regulate cristae structure. This cristae regulation is independent of OPA1's role in mitochondrial fusion, since an OPA1 mutant that can still oligomerize but has no fusion activity was able to maintain cristae structure. Importantly, OPA1 was required for resistance to starvation-induced cell death, for mitochondrial respiration, for growth in galactose media and for maintenance of ATP synthase assembly, independently of its fusion activity. We identified mitochondrial solute carriers (SLC25A) as OPA1 interactors and show that their pharmacological and genetic blockade inhibited OPA1 oligomerization and function. Thus, we propose a novel way in which OPA1 senses energy substrate availability, which modulates its function in the regulation of mitochondrial architecture in a SLC25A protein-dependent manner.",
"title": "OPA1-dependent cristae modulation is essential for cellular adaptation to metabolic demand."
},
{
"docid": "86129154",
"text": "Somatic cell nuclear transfer allows trans-acting factors present in the mammalian oocyte to reprogram somatic cell nuclei to an undifferentiated state. We show that four factors (OCT4, SOX2, NANOG, and LIN28) are sufficient to reprogram human somatic cells to pluripotent stem cells that exhibit the essential characteristics of embryonic stem (ES) cells. These induced pluripotent human stem cells have normal karyotypes, express telomerase activity, express cell surface markers and genes that characterize human ES cells, and maintain the developmental potential to differentiate into advanced derivatives of all three primary germ layers. Such induced pluripotent human cell lines should be useful in the production of new disease models and in drug development, as well as for applications in transplantation medicine, once technical limitations (for example, mutation through viral integration) are eliminated.",
"title": "Induced pluripotent stem cell lines derived from human somatic cells."
},
{
"docid": "34615397",
"text": "The human tuberculous granuloma provides the morphological basis for local immune processes central to the outcome of tuberculosis. Because of the scarcity of information in human patients, the aim of the present study was to gain insights into the functional and structural properties of infiltrated tissue. To this end, the mycobacterial load in lesions and dissemination to different tissue locations were investigated, as well as distribution, biological functions, and interactions of host immune cells. Analysis of early granuloma formation in formerly healthy lung tissue revealed a spatio-temporal sequence of cellular infiltration to sites of mycobacterial infection. A general structure of the developing granuloma was identified, comprising an inner cell layer with few CD8(+) cells surrounding the necrotic centre and an outer area of lymphocyte infiltration harbouring mycobacteria-containing antigen-presenting cells as well as CD4(+), CD8(+), and B cells in active follicle-like centres resembling secondary lymphoid organs. It is concluded that the follicular structures in the peripheral rim of granulomas serve as a morphological substrate for the orchestration of the enduring host response in pulmonary tuberculosis.",
"title": "Human tuberculous granulomas induce peripheral lymphoid follicle-like structures to orchestrate local host defence in the lung."
},
{
"docid": "22241778",
"text": "The human kidneys filter 180 l of blood every day via about 2.5 million glomeruli. The three layers of the glomerular filtration apparatus consist of fenestrated endothelium, specialized extracellular matrix known as the glomerular basement membrane (GBM) and the podocyte foot processes with their modified adherens junctions known as the slit diaphragm (SD). In this study we explored the contribution of podocyte beta1 integrin signaling for normal glomerular function. Mice with podocyte specific deletion of integrin beta1 (podocin-Cre beta1-fl/fl mice) are born normal but cannot complete postnatal renal development. They exhibit detectable proteinuria on day 1 and die within a week. The kidneys of podocin-Cre beta1-fl/fl mice exhibit normal glomerular endothelium but show severe GBM defects with multilaminations and splitting including podocyte foot process effacement. The integrin linked kinase (ILK) is a downstream mediator of integrin beta1 activity in epithelial cells. To further explore whether integrin beta1-mediated signaling facilitates proper glomerular filtration, we generated mice deficient of ILK in the podocytes (podocin-Cre ILK-fl/fl mice). These mice develop normally but exhibit postnatal proteinuria at birth and die within 15 weeks of age due to renal failure. Collectively, our studies demonstrate that podocyte beta1 integrin and ILK signaling is critical for postnatal development and function of the glomerular filtration apparatus.",
"title": "Integrin beta1-mediated matrix assembly and signaling are critical for the normal development and function of the kidney glomerulus."
},
{
"docid": "6308416",
"text": "Coordinated cell movements in epithelial layers are essential for proper tissue morphogenesis and homeostasis, but our understanding of the mechanisms that coordinate the behavior of multiple cells in these processes is far from complete. Recent experiments with Madin-Darby canine kidney epithelial monolayers revealed a wave-like pattern of injury-induced MAPK activation and showed that it is essential for collective cell migration after wounding. To investigate the effects of the different aspects of wounding on cell sheet migration, we engineered a system that allowed us to dissect the classic wound healing assay. We studied Madin-Darby canine kidney sheet migration under three different conditions: 1) the classic wound healing assay, 2) empty space induction, where a confluent monolayer is grown adjacent to a slab of polydimethylsiloxane and the monolayer is not injured but allowed to migrate upon removal of the slab, and 3) injury via polydimethylsiloxane membrane peel-off, where an injured monolayer migrates onto plain tissue culture surface, as in the case of empty space induction allowing for direct comparison. By tracking the motion of individual cells within the sheet under these three conditions, we show how the dynamics of the individual cells' motion is responsible for the coordinated migration of the sheet and is coordinated with the activation of ERK1/2 MAPK. In addition, we demonstrate that the propagation of the waves of MAPK activation depends on the generation of reactive oxygen species at the wound edge.",
"title": "Role of boundary conditions in an experimental model of epithelial wound healing."
},
{
"docid": "26283293",
"text": "Eukaryotic cells are compartmentalized into membrane-bounded organelles whose functions rely on lipid trafficking to achieve membrane-specific compositions of lipids. Here we focused on the Ups1-Mdm35 system, which mediates phosphatidic acid (PA) transfer between the outer and inner mitochondrial membranes, and determined the X-ray structures of Mdm35 and Ups1-Mdm35 with and without PA. The Ups1-Mdm35 complex constitutes a single domain that has a deep pocket and flexible Ω-loop lid. Structure-based mutational analyses revealed that a basic residue at the pocket bottom and the Ω-loop lid are important for PA extraction from the membrane following Ups1 binding. Ups1 binding to the membrane is enhanced by the dissociation of Mdm35. We also show that basic residues around the pocket entrance are important for Ups1 binding to the membrane and PA extraction. These results provide a structural basis for understanding the mechanism of PA transfer between mitochondrial membranes.",
"title": "Structural and mechanistic insights into phospholipid transfer by Ups1–Mdm35 in mitochondria"
},
{
"docid": "8247597",
"text": "Mutations and deletions in the mitochondrial genome (mtDNA), as well as instability of the nuclear genome, are involved in multiple human diseases. Here, we report that in Saccharomyces cerevisiae, loss of mtDNA leads to nuclear genome instability, through a process of cell-cycle arrest and selection we define as a cellular crisis. This crisis is not mediated by the absence of respiration, but instead correlates with a reduction in the mitochondrial membrane potential. Analysis of cells undergoing this crisis identified a defect in iron-sulfur cluster (ISC) biogenesis, which requires normal mitochondrial function. We found that downregulation of nonmitochondrial ISC protein biogenesis was sufficient to cause increased genomic instability in cells with intact mitochondrial function. These results suggest mitochondrial dysfunction stimulates nuclear genome instability by inhibiting the production of ISC-containing protein(s), which are required for maintenance of nuclear genome integrity. For a video summary of this article, see the PaperFlick file available with the online Supplemental Data.",
"title": "Mitochondrial Dysfunction Leads to Nuclear Genome Instability via an Iron-Sulfur Cluster Defect"
},
{
"docid": "4447055",
"text": "Contusive spinal cord injury leads to a variety of disabilities owing to limited neuronal regeneration and functional plasticity. It is well established that an upregulation of glial-derived chondroitin sulphate proteoglycans (CSPGs) within the glial scar and perineuronal net creates a barrier to axonal regrowth and sprouting. Protein tyrosine phosphatase σ (PTPσ), along with its sister phosphatase leukocyte common antigen-related (LAR) and the nogo receptors 1 and 3 (NgR), have recently been identified as receptors for the inhibitory glycosylated side chains of CSPGs. Here we find in rats that PTPσ has a critical role in converting growth cones into a dystrophic state by tightly stabilizing them within CSPG-rich substrates. We generated a membrane-permeable peptide mimetic of the PTPσ wedge domain that binds to PTPσ and relieves CSPG-mediated inhibition. Systemic delivery of this peptide over weeks restored substantial serotonergic innervation to the spinal cord below the level of injury and facilitated functional recovery of both locomotor and urinary systems. Our results add a new layer of understanding to the critical role of PTPσ in mediating the growth-inhibited state of neurons due to CSPGs within the injured adult spinal cord.",
"title": "Modulation of the proteoglycan receptor PTPσ promotes recovery after spinal cord injury"
}
] |
7927
|
What does the -V indicate on MKC ticker
|
[
{
"docid": "573958",
"text": "MKC is non-voting stock, MKC/V is voting stock. Ofter times you'll see two or more stock symbols for a company. These usually reflect different classes of stocks. For example, voting vs. non-voting (as in this case) or preferred vs non-preferred stock.",
"title": ""
}
] |
[
{
"docid": "193050",
"text": "TIAA-Cref has their Social Choice Equity Fund, which is a Large Blend primarily equity fund that invests given the following consideration: The Fund primarily invests in companies that are screened by MSCI Inc. (“MSCI”) to favor companies that meet or exceed certain environmental, social and governance (“ESG”) criteria. The Fund does this by investing in U.S. companies included in one or more MSCI ESG Indices that meet or exceed the screening criteria described below. Prior to being eligible for inclusion in the MSCI ESG Indices, companies are subject to an ESG performance evaluation conducted by MSCI, consisting of numerous factors. The ESG evaluation process favors companies that are: (i) strong stewards of the environment; (ii) devoted to serving local communities where they operate and to human rights and philanthropy; (iii) committed to higher labor standards for their own employees and those in the supply chain; (iv) dedicated to producing high-quality and safe products; and (v) managed in an exemplary and ethical manner. https://www.tiaa.org/public/offer/products/mutual-funds/responsible-investing",
"title": ""
},
{
"docid": "517161",
"text": "\"Considering the fact that you are so unaware of how to find such data, I find it very very hard to believe that you actually need it. \"\"All trade and finance data for as much tickers and markets as possible.\"\" Wtf does that even mean. You could be referencing thousands of different types of data for any given \"\"ticker\"\" with a statement so vague. What are you looking for?\"",
"title": ""
},
{
"docid": "11184",
"text": "\"The Dividend Discount Model is based on the concept that the present value of a stock is the sum of all future dividends, discounted back to the present. Since you said: dividends are expected to grow at a constant rate in perpetuity ... the Gordon Growth Model is a simple variant of the DDM, tailored for a firm in \"\"steady state\"\" mode, with dividends growing at a rate that can be sustained forever. Consider McCormick (MKC), who's last dividend was 31 cents, or $1.24 annualized. The dividend has been growing just a little over 7% annually. Let's use a discount, or hurdle rate of 10%. MKC closed today at $50.32, for what it's worth. The model is extremely sensitive to inputs. As g approaches r, the stock price rises to infinity. If g > r, stock goes negative. Be conservative with 'g' -- it must be sustainable forever. The next step up in complexity is the two-stage DDM, where the company is expected to grow at a higher, unsustainable rate in the early years (stage 1), and then settling down to the terminal rate for stage 2. Stage 1 is the present value of dividends during the high growth period. Stage 2 is the Gordon Model, starting at the end of stage 1, and discounting back to the present. Consider Abbott Labs (ABT). The current annual dividend is $1.92, the current dividend growth rate is 12%, and let's say that continues for ten years (n), after which point the growth rate is 5% in perpetuity. Again, the discount rate is 10%. Stage 1 is calculated as follows: Stage 2 is GGM, using not today's dividend, but the 11th year's dividend, since stage 1 covered the first ten years. 'gn' is the terminal growth, 5% in our case. then... The value of the stock today is 21.22 + 51.50 = 72.72 ABT closed today at $56.72, for what it's worth.\"",
"title": ""
},
{
"docid": "583941",
"text": "\"Answering this question is weird, because it is not really precise in what you mean. Do you want all stocks in the US? Do you want a selection of stocks according to parameters? Do you just want a cool looking graph? However, your possible misuse of the word derivative piqued my interest. Your reference to gold and silver seems to indicate that you do not know what a derivative actually is. Or what it would do in a portfolio. The straightforward way to \"\"see\"\" an efficient frontier is to do the following. For a set of stocks (in this case six \"\"randomly\"\" selected ones): library(quantmod) library(fPortfolio) library(PerformanceAnalytics) getSymbols(c(\"\"STZ\"\", \"\"RAI\"\", \"\"AMZN\"\", \"\"MSFT\"\", \"\"TWX\"\", \"\"RHT\"\"), from = \"\"2012-06-01\"\", to = \"\"2017-06-01\"\") returns <- NULL tickerlist <- c(\"\"STZ\"\", \"\"RAI\"\", \"\"AMZN\"\", \"\"MSFT\"\", \"\"TWX\"\", \"\"RHT\"\") for (ticker in tickerlist){ returns <- cbind(returns, monthlyReturn(Ad(eval(as.symbol(ticker))))) } colnames(returns) <- tickerlist returns <- as.timeSeries(returns) frontier <- portfolioFrontier(returns) png(\"\"frontier.png\"\", width = 800, height = 600) plot(frontier, which = \"\"all\"\") dev.off() minvariancePortfolio(returns, constraints = \"\"LongOnly\"\") Portfolio Weights: STZ RAI AMZN MSFT TWX RHT 0.1140 0.3912 0.0000 0.1421 0.1476 0.2051 Covariance Risk Budgets: STZ RAI AMZN MSFT TWX RHT 0.1140 0.3912 0.0000 0.1421 0.1476 0.2051 Target Returns and Risks: mean Cov CVaR VaR 0.0232 0.0354 0.0455 0.0360 https://imgur.com/QIxDdEI The minimum variance portfolio of these six assets has a mean return is 0.0232 and variance is 0.0360. AMZN does not get any weight in the portfolio. It kind of means that the other assets span it and it does not provide any additional diversification benefit. Let us add two ETFs that track gold and silver to the mix, and see how little difference it makes: getSymbols(c(\"\"GLD\"\", \"\"SLV\"\"), from = \"\"2012-06-01\"\", to = \"\"2017-06-01\"\") returns <- NULL tickerlist <- c(\"\"STZ\"\", \"\"RAI\"\", \"\"AMZN\"\", \"\"MSFT\"\", \"\"TWX\"\", \"\"RHT\"\", \"\"GLD\"\", \"\"SLV\"\") for (ticker in tickerlist){ returns <- cbind(returns, monthlyReturn(Ad(eval(as.symbol(ticker))))) } colnames(returns) <- tickerlist returns <- as.timeSeries(returns) frontier <- portfolioFrontier(returns) png(\"\"weights.png\"\", width = 800, height = 600) weightsPlot(frontier) dev.off() # Optimal weights out <- minvariancePortfolio(returns, constraints = \"\"LongOnly\"\") wghts <- getWeights(out) portret1 <- returns%*%wghts portret1 <- cbind(monthprc, portret1)[,3] colnames(portret1) <- \"\"Optimal portfolio\"\" # Equal weights wghts <- rep(1/8, 8) portret2 <- returns%*%wghts portret2 <- cbind(monthprc, portret2)[,3] colnames(portret2) <- \"\"Equal weights portfolio\"\" png(\"\"performance_both.png\"\", width = 800, height = 600) par(mfrow=c(2,2)) chart.CumReturns(portret1, ylim = c(0, 2)) chart.CumReturns(portret2, ylim = c(0, 2)) chart.Drawdown(portret1, main = \"\"Drawdown\"\", ylim = c(-0.06, 0)) chart.Drawdown(portret2, main = \"\"Drawdown\"\", ylim = c(-0.06, 0)) dev.off() https://imgur.com/sBHGz7s Adding gold changes the minimum variance mean return to 0.0116 and the variance stays about the same 0.0332. You can see how the weights change at different return and variance profiles in the picture. The takeaway is that adding gold decreases the return but does not do a lot for the risk of the portfolio. You also notice that silver does not get included in the minimum variance efficient portfolio (and neither does AMZN). https://imgur.com/rXPbXau We can also compare the optimal weights to an equally weighted portfolio and see that the latter would have performed better but had much larger drawdowns. Which is because it has a higher volatility, which might be undesirable. --- Everything below here is false, but illustrative. So what about the derivative part? Let us assume you bought an out of the money call option with a strike of 50 on MSFT at the beginning of the time series and held it to the end. We need to decide on the the annualized cost-of-carry rate, the annualized rate of interest, the time to maturity is measured in years, the annualized volatility of the underlying security is proxied by the historical volatility. library(fOptions) monthprc <- Ad(MSFT)[endpoints(MSFT, \"\"months\"\")] T <- length(monthprc) # 60 months, 5 years vol <- sd(returns$MSFT)*sqrt(12) # annualized volatility optprc <- matrix(NA, 60, 1) for (t in 1:60) { s <- as.numeric(monthprc[t]) optval <- GBSOption(TypeFlag = \"\"c\"\", S = s, X = 50, Time = (T - t) / 12, r = 0.001, b = 0.001, sigma = vol) optprc[t] <- optval@price } monthprc <- cbind(monthprc, optprc) colnames(monthprc) <- c(\"\"MSFT\"\", \"\"MSFTCall50\"\") MSFTCall50rets <- monthlyReturn(monthprc[,2]) colnames(MSFTCall50rets) <- \"\"MSFTCall50rets\"\" returns <- merge(returns, MSFTCall50rets) wghts <- rep(1/9, 9) portret3 <- returns%*%wghts portret3 <- cbind(monthprc, portret3)[,3] colnames(portret3) <- \"\"Equal weights derivative portfolio\"\" png(\"\"performance_deriv.png\"\", width = 800, height = 600) par(mfrow=c(2,2)) chart.CumReturns(portret2, ylim = c(0, 4.5)) chart.CumReturns(portret3, ylim = c(0, 4.5)) chart.Drawdown(portret2, main = \"\"Drawdown\"\", ylim = c(-0.09, 0)) chart.Drawdown(portret3, main = \"\"Drawdown\"\", ylim = c(-0.09, 0)) dev.off() https://imgur.com/SZ1xrYx Even though we have a massively profitable instrument in the derivative. The portfolio analysis does not include it because of the high volatility. However, if we just use equal weighting and essentially take a massive position in the out of the money call (which would not be possible in real life), we get huge drawdowns and volatility, but the returns are almost two fold. But nobody will sell you a five year call. Others can correct any mistakes or misunderstandings in the above. It hopefully gives a starting point. Read more at: https://en.wikipedia.org/wiki/Modern_portfolio_theory https://en.wikipedia.org/wiki/Option_(finance) The imgur album: https://imgur.com/a/LoBEY\"",
"title": ""
},
{
"docid": "472663",
"text": "\"An Exchange-Traded Fund (ETF) is a special type of mutual fund that is traded on the stock exchange like a stock. To invest, you buy it through a stock broker, just as you would if you were buying an individual stock. When looking at a mutual fund based in the U.S., the easiest way to tell whether or not it is an ETF is by looking at the ticker symbol. Traditional mutual funds have ticker symbols that end in \"\"X\"\", and ETFs have ticker symbols that do not end in \"\"X\"\". The JPMorgan Emerging Markets Equity Fund, with ticker symbol JFAMX, is a traditional mutual fund, not an ETF. JPMorgan does have ETFs; the JPMorgan Diversified Return Emerging Markets Equity ETF, with ticker symbol JPEM, is an example. This ETF invests in similar stocks as JFAMX; however, because it is an index-based fund instead of an actively managed fund, it has lower fees. If you aren't sure about the ticker symbol, the advertising/prospectus of any ETF should clearly state that it is an ETF. (In the example of JPEM above, they put \"\"ETF\"\" right in the fund name.) If you don't see ETF mentioned, it is most likely a traditional mutual fund. Another way to tell is by looking at the \"\"investment minimums\"\" of the fund. JFAMX has a minimum initial investment of $1000. ETFs, however, do not have an investment minimum listed; because it is traded like a stock, you simply buy whole shares at whatever the current share price is. So if you look at the \"\"Fees and Investment Minimums\"\" section of the JPEM page, you'll see the fees listed, but not any investment minimums.\"",
"title": ""
},
{
"docid": "350191",
"text": "\"Things are in fact more complicated. It really depends what you mean by \"\"ticker\"\" and who gave you this ticker. There is several codes to identify a security: The Bloomberg code contains a code to identify the exchange as in ALU:FP the FP part refers to Euronext Paris. The RIC code works the same way but with a different convention. Exchanges are identified by the MIC code.(they are in fact divided in market segments with each market segment having a main market segment) ISIN and SEDOL codes do not provide informations about the exchange so they are usually given with a MIC. There is no guarantee that Reuters and Bloomberg won't use the same company code to refer to different company. But they usually use the exchange ticker. This ticker is requested by each company and can be anything. They are accepted most of the time. But sometimes to avoid confusion some requests are rejected. (For instance FBI ticker was refused) For more info read: The evolution of ticker symbols Financial providers like Bloomberg provides services to be informed when a security is added/removed from a market.\"",
"title": ""
},
{
"docid": "195089",
"text": "Willis Group Holdings Set to Join the S&P 500; Fossil Group to Join S&P MidCap 400; Adeptus Health to Join S&P SmallCap 600 notes in part for the S & P case: Willis Group Holdings plc (NYSE:WSH) will replace Fossil Group Inc. (NASD:FOSL) in the S&P 500, and Fossil Group will replace Towers Watson & Co. (NASD:TW) in the S&P MidCap 400 after the close of trading on Monday, January 4. Willis Group is merging with Towers Watson in a deal expected to be completed on or about that date pending final conditions. Post merger, Willis Group Holdings will change its name to Willis Towers Watson plc and trade under the ticker symbol “WLTW”. Fossil has a market capitalization that is more representative of the midcap market space. As of Jan. 8, Fossil is about $1.44B in market cap and Willis is $21.02B for those wondering. Apple with a market cap of $540.58B is 3.26% of the index making the entire index worth approximately $16,582.21B, so Fossil is worth .00868% of the overall index for those wanting some numbers here. Thus, if a company acquires another and becomes bigger than there can be replacements made in those indices that have an artificial number of small members. Alternatively, a member may be removed for lack of representation where it is just so small compared to other companies that may be a better fit as some indices could be viewed as actively managed in a sense. In contrast, there are indices like those from Russell, known for the Russell 2000 small-cap index: Q: Why don't you reconstitute the indexes more often than once a year? A: Maintaining representative indexes must be weighed against the costs associated with making frequent changes to index constituents (namely, buying and selling stocks). The Russell Indexes are annually reconstituted because our research has shown that this strikes a reasonable balance between accuracy and cost. We originally reconstituted our indexes quarterly, then semi-annually, but found these options to be suboptimal. Our extensive research demonstrates that annual reconstitution accurately represents the capitalization segments and minimizes the turnover required to reflect the segments as they change. Thus there can be different scenarios. Then there can be the effect on index funds when price-weighted indices like the Dow Jones Industrial Average has a member that does a stock split that causes some rebalancing too. On the DJIA Divisor: The Dow Jones Industrial Average (DJIA) is a price-weighted index that is calculated by dividing the sum of the prices of the 30 component stocks (Dow Jones Industrial Average components) by a number called the DJIA Divisor or Dow Divisor . The index divisor is updated periodically and adjusted to offset the effect of stock splits, bonus issues or any change in the component stocks included in the DJIA. This is done in order to keep the index value consistent.",
"title": ""
},
{
"docid": "341293",
"text": "\"When they entered Bankruptcy they changed their stock symbol from AAMR to AAMRQ. The Q tells investors that the company i in Bankruptcy. This i what the SEC says about the Q: \"\"Q\"\" Added To Stock Ticker Symbol When a company is involved in bankruptcy proceedings, the letter \"\"Q\"\" is added to the end of the company's stock ticker symbol. In most cases, when a company emerges from bankruptcy, the reorganization plan will cancel the existing equity stock and the old shares will be worthless. Given that risk, before purchasing stock in a bankrupt company, investors should read the company's proposed plan of reorganization. For more information about the impact of bankruptcy proceedings on securities, please read our online publication, Corporate Bankruptcy. The risks are they never recover, or that the old shares have nothing to do with new company. Many investors don't understand this. Recently some uninformed investors(?) tried to get a jump on the Twitter IPO by purchasing share of what they thought was Twitter but was instead the bankrupt company Tweeter Home Entertainment. Shares of Tweeter Home Entertainment, a Boston-based consumer electronics chain that filed for bankruptcy in 2007, soared Friday in a case of mistaken identity on Wall Street. Apparently, some investors confused Tweeter, which trades under the symbol TWTRQ, with Twitter and piled into the penny stock. Tweeter, which trades over the counter, opened at 2 cents a share and jumped as much as 15 cents — or 1,800 percent — before regulators halted trading. Almost 15 million shares had changed hands at that point, while the average daily volume is closer to 150,000. Sometimes it does happen that the new company does give some value to the old investors, but more often then not the old investors are completely wiped out.\"",
"title": ""
},
{
"docid": "3118",
"text": "Dividends are normally paid in cash, so don't generally affect your portfolio aside from a slight increase to 'cash'. You get a check for them, or your broker would deposit the funds into a money-market account for you. There is sometimes an option to re-invest dividends, See Westyfresh's answer regarding Dividend Re-Investment Plans. As Tom Au described, the dividends are set by the board of directors and announced. Also as he indicated just before the 'record' date, a stock which pays dividends is worth slightly more (reflecting the value of the dividend that will be paid to anyone holding the stock on the record date) and goes down by the dividend amount immediately after that date (since you'd now have to hold the stock till the next record date to get a dividend) In general unless there's a big change in the landscape (such as in late 2008) most companies pay out about the same dividend each time, and changes to this are sometimes seen by some as 'indicators' of company health and such news can result in movement in the stock price. When you look at a basic quote on a ticker symbol there is usually a line for Div/yeild which gives the amount of dividend paid per share, and the relative yeild (as a percentage of the stock price). If a company has been paying dividends, this field will have values in it, if a company does not pay a dividend it will be blank or say NA (depending on where you get the quote). This is the easiest way to see if a company pays a dividend or not. for example if you look at this quote for Google, you can see it pays no dividend Now, in terms of telling when and how much of a dividend has been paid, most financial sites have the option when viewing a stock chart to show the dividend payments. If you expand the chart to show at least a year, you can see when and how much was paid in terms of dividends. For example you can see from this chart that MSFT pays dividends once a quarter, and used to pay out 13 cents, but recently changed to 16 cents. if you were to float your mouse over one of those icons it would also give the date the dividend was paid.",
"title": ""
},
{
"docid": "397445",
"text": "\"That share class may not have a ticker symbol though \"\"Black Rock MSCI ACWI ex-US Index\"\" does have a ticker for \"\"Investor A\"\" shares that is BDOAX. Some funds will have multiple share classes that is a way to have fees be applied in various ways. Mutual fund classes would be the SEC document about this if you want a government source within the US around this. Something else to consider is that if you are investing in a \"\"Fund of funds\"\" is that there can be two layers of expense ratios to consider. Vanguard is well-known for keeping its expenses low.\"",
"title": ""
},
{
"docid": "369424",
"text": "\"The official source is the most recent Form 13F that Berkshire Hathaway, which is filed with the Securities & Exchange Commission on a quarterly basis . You can find it through the SEC filing search engine, using BRKA as the ticker symbol. and then looking for the filings marked 13-FR or 13-FR/A (the \"\"/A\"\" indicates an amended filing). As you can see by looking at the 13-F filed for the quarter ending September 30 , the document isn't pretty or necessarily easy to read, hence the popularity of sites such as those that Chad linked to. It is, though, the truly official source from which websites tracking the Berkshire Hathaway portfolio derive their information.\"",
"title": ""
},
{
"docid": "323133",
"text": "\"I said the majority, not ALL. (And the vast majority of people -- again even within the \"\"sciences\"\" -- are in fact mediocrities). That doesn't mean it take some \"\"super-genius\"\" to see past the fraud, but it does take a sharp mind, AND it then takes an interest and time to look into the evidence (what little there actually is). Many people within the hard sciences are more than capable of seeing through the fraud and foolishness of psychology/psychiatry. Indeed, many *have* done so. (Cf [Feynman](http://www.rationalskepticism.org/psychology/richard-feynman-briefly-on-psychology-t967.html), and of course the aforementioned [John Ioannidis](psychcentral.com/blog/archives/2010/10/19/what-research-can-you-believe/) who has debunked a LOT of so called \"\"research\"\" in both psychiatry and other medical \"\"science\"\" research). But far more often those with sharp minds are busy with a lot of other endeavors, and so long as they have no driving need, they do not really examine other fields to much dept (in most cases they do not investigate other fields at all). What is more is that psychologists & [psychiatrists themselves know](http://www.youtube.com/watch?v=-P6_FwpVo_s) (and [when put on the spot will admit that there is no real science behind the malarkey](http://www.youtube.com/watch?v=atsCp2SErog) or the drugs) that they sell -- not that they really care of course.\"",
"title": ""
},
{
"docid": "265404",
"text": "What I ended up doing was finding where each ticker of Novo was registered (what exchange), then individually looking up the foreign taxation rules of the containing country. Luckily, most companies only have a few tickers so this wasn't too hard in the end.",
"title": ""
},
{
"docid": "27303",
"text": "Options - yes we can :) Options tickers on Yahoo! Finance will be displayed as per new options symbology announced by OCC. The basic parts of new option symbol are: Root symbol + Expiration Year(yy)+ Expiration Month(mm)+ Expiration Day(dd) + Call/Put Indicator (C or P) + Strike price Ex.: AAPL January 19 2013, Put 615 would be AAPL130119P00615000 http://finance.yahoo.com/q?s=AAPL130119P00615000&ql=1 Futures - yes as well (: Ex.: 6A.M12.E would be 6AM12.CME using Yahoo Finance symbology. (simple as that, try it out) Get your major futures symbols from here: http://quotes.ino.com/exchanges/exchange.html?e=CME",
"title": ""
},
{
"docid": "165973",
"text": "It depends on what site you're looking on and what exchange they're pulling the data from. Even though funds and stocks are called the same thing, they have different ticker symbols in each country's exchange or could be traded as pink sheet stocks in the US. If a company or fund is based in another country (like Canada or the UK) they probably also trade on that country's exchange (Toronto or London) under a different symbol. This can cause a lot of confusion when researching these tickers.",
"title": ""
},
{
"docid": "278113",
"text": "Reading this made me think of [this](https://www.youtube.com/watch?v=-s1s5K52zEQ). I wish you luck if you consider yourself an authority on a subject you have practically no exposure to, but hey, what does a hiring manager know? I mean, you're about to start an internship, so obviously everyone should want to know your opinion on the future of the market.",
"title": ""
},
{
"docid": "97075",
"text": "Steve Keen says otherwise, he says Banks CAN create a Quadrillion dollars, as long as there are willing borrowers. : http://www.youtube.com/watch?v=zc_fpGfyqGE. http://www.youtube.com/watch?v=4sSfPkIUHPk&feature=share why does m2 seem like exponential? how can fractional reserve do something like that? unpossible. seems like only an explosive growth in either productivity or profits through slave labor globalization or speculative derivatives can do something like that.",
"title": ""
},
{
"docid": "47276",
"text": "Presumably you mean to ask what happens if State Street files chapter 7 bankruptcy, since not all bankruptcy proceedings end in liquidation. SPY is a well known ticker, I can't imagine that there wouldn't be an eager bank willing to pay to pick up that ticker and immediately acquire all the assets related to it. The most likely scenario is that another bank would assume control of the ticker and assets, and the shares would continue trading as they always have. A less likely scenario is that no other financial institution wanted to acquire SPY, and the shares would be liquidated and the proceeds would go to the owners of shares of the ETF. Since the underlying assets are in companies that have actual value, the shares shouldn't trade at much of a discount prior to liquidation. Additionally, if there is a black swan event, there will probably be losses on the underlying assets, so it might even be helpful if the SPY fund was tied up in legal proceedings while everyone gets their heads straight in the market.",
"title": ""
},
{
"docid": "318774",
"text": "NYSE started allowing four letter tickers around 2009. NASDAQ allows 4-5 letter tickers. I guess they'll keep increasing when / if needed. Companies are allowed to change tickers, although there are costs. Tickers in the US are assigned through a single entity. Companies that are new need to take something that's open. http://www.wsj.com/articles/SB124296050986346159 I see that you're in Australia, but, since there aren't really that many options to deal with the problem that you mentioned, I'd guess that you'll ultimately do the same. Not sure about how tickers are assigned there though.",
"title": ""
},
{
"docid": "339268",
"text": "\"You cannot determine this solely by the ticker length. However, there are some conventions that may help steer you there. Nasdaq has 2-4 base letters BATS has 4 base letters NYSE equity securities have 1-4 base letters. NYSE Mkt (formerly Amex) have 1-4 base letters. NYSE Arca has 4 base letters OTC has 4 base letters. Security types other than equities may have additional letters added, and each exchange (and data vendors) have different conventions for how this is handled. So if you see \"\"T\"\" for a US-listed security it would be only be either NASDAQ, NYSE or NYSE Mkt. If you see \"\"ANET\"\" then you cannot tell which exchange it is listed on. (In this case, ANET Arista Networks is actually a NYSE stock). For some non-equity security types, such as hybrids, and debt instruments, some exchanges add \"\"P\"\" to the end for \"\"preferreds\"\" (Nasdaq and OTC) and NYSE/NYSE Mkt have a variety of methods (including not adding anything) to the ticker. Examples include NYSE:TFG, NYSEMkt:IPB, Nasdaaq: AGNCP, Nasdaq:OXLCN. It all becomes rather confusing given the changes in conventions over the years. Essentially, you require data that provides you with ticker, listing location and security type. The exchanges allocate security tickers in conjunction with the SEC so there are no overlaps. eg. The same ticker cannot represent two different securities. However, tickers can be re-used. For example, the ticker AB has been used by the following companies:\"",
"title": ""
},
{
"docid": "37568",
"text": "SECTION | CONTENT :--|:-- Title | Bitcoin explained real easy. Raise Your Frequency S1.E1 Description | Bitcoin explained real easy so anyone can understand what it is and how it works.. You decide which system you prefer: current money system: https://www.youtube.com/watch?v=G9IH-XKQpOI current money system: https://www.youtube.com/watch?v=PhSIfVyvDdM current money system: https://www.youtube.com/watch?v=JuP2hH0Kpro current money system: https://www.youtube.com/watch?v=Bx5Sc3vWefE Bitcoin: https://medium.com/zapchain-magazine/the-10-best-videos-to-watch-to-learn-about-bitcoin-c34f98f2fed... Length | 0:26:48 **** ^(I am a bot, this is an auto-generated reply | )^[Info](https://www.reddit.com/u/video_descriptionbot) ^| ^[Feedback](https://www.reddit.com/message/compose/?to=video_descriptionbot&subject=Feedback) ^| ^(Reply STOP to opt out permanently)",
"title": ""
},
{
"docid": "94159",
"text": "\"I don't have anything definitive, but in general positions in a company are not affected materially by what is called a corporate action. \"\"Corp Actions\"\" can really be anything that affects the details of a stock. Common examples are a ticker change, or exchange change, IPO (ie a new ticker), doing a split, or merging with another ticker. All of these events do not change the total value of people's positions. If a stock splits, you might have more shares, but they are worth less per share. A merger is quite similar to a split. The old company's stock is converted two the new companies stock at some ratio (ie 10 shares become 1 share) and then converted 1-to-1 to the new symbol. Shorting a stock that splits is no different. You shorted 10 shares, but after the split those are now 100 shares, when you exit the position you have to deliver back 100 \"\"new\"\" shares, though dollar-for-dollar they are the same total value. I don't see why a merger would affect your short position. The only difference is you are now shorting a different company, so when you exit the position you'll have to deliver shares of the new company back to the brokerage where you \"\"borrowed\"\" the shares you shorted.\"",
"title": ""
},
{
"docid": "252039",
"text": "Do you want to know How to Buy Bitcoins or How to Make Money in Bitcoin Investments. First of all, you should know What is Bitcoin? and What is Cryptocurrency? Through our this https://www.youtube.com/watch?v=xDIRVGkeONY video link you will get all the information whatever you want to know about Bitcoins. https://www.youtube.com/watch?v=xDIRVGkeONY",
"title": ""
},
{
"docid": "172703",
"text": "No, some of Vanguard's funds are index funds like their Total Stock Market Index and 500 Index. In contrast, there are funds like Vanguard PRIMECAP and Vanguard Wellington that are actively managed. There are index funds in both open-end and exchange-traded formats. VTI is the ticker for Vanguard's Total Stock Market ETF while VTSMX is an open-end mutual fund format. VOO would be the S & P 500 ETF ticker while VFINX is one of the open-end mutual fund tickers, where VIIIX has a really low expense ratio but a pretty stiff minimum to my mind. As a general note, open-end mutual funds will generally have a 5 letter ticker ending in X while an ETF will generally be shorter at 3 or 4 letters in length.",
"title": ""
},
{
"docid": "323749",
"text": "\"There are a number of ways to measure such things and they are generally called \"\"sentiment indicators\"\". The ones that I have seen \"\"work\"\", in the sense that they show relatively high readings near market tops and relatively low readings near market bottoms. The problem is that there are no thresholds that work consistently. For example, at one market top a sentiment indicator may read 62. At the next market top that same indicator might read 55. So what threshold do you use next time? Maybe the top will come at 53, or maybe it will not come until 65. There was a time when I could have listed examples for you with the names of the indicators and what they signaled and when. But I gave up on such things years ago after seeing such wide variation. I have been at this a long time (30+ years), and I have not found anything that works as well as we would like at identifying a top in real time. The best I have found (although it does give false signals) is a drop in price coupled with a bearish divergence in breadth. The latter is described in \"\"Stan Weinstein's Secrets For Profiting in Bull and Bear Markets\"\". Market bottoms are a little less difficult to identify in real time. One thing I would suggest if you think that there is some way to get a significant edge in investing, is to look at the results of Mark Hulbert's monitoring of newsletters. Virtually all of them rise and fall with the market and almost none are able to beat buy and hold of the Wilshire 5000 over the long term.\"",
"title": ""
},
{
"docid": "222075",
"text": "Oh, God! I remember that thing. Could this be considered *peak bullshit product*? This stupid juicer is one of the best examples of why you shouldn't throw technology at something that isn't a problem. Did people have a problem obtaining juice?! Does WiFi solve that problem? To give a counter example, I reckon this: https://shapertools.com/ is one of the BEST technological solutions to a problem that I've seen in a long time, and could be the beginning of a whole range of smart tools. EDIT: people are doubting that is exists. People are using the early models. I first saw the device while watching this video. https://www.youtube.com/watch?v=lfmrvxB154w&feature=youtu.be&t=3m10s Long video of people using and discussing it: https://www.youtube.com/watch?v=p_wk3q8jWcs If you check YouTube, there are loads of videos. https://www.youtube.com/results?search_query=shaper+origin",
"title": ""
},
{
"docid": "475984",
"text": "\"Thanks for pointing out [the study](http://papers.ssrn.com/sol3/papers.cfm?abstract_id=1748851). It's a slightly different cause than what I was describing when I posted this. Specifically, they show an effect not when the names get confused, but rather when the name similarity simply brings more attention to the stock. I was surprised nobody mentioned that in response to my post. But also interesting is that they had to control for simple confusion between stock symbols, which implies that ticker confusion has a known effect. So I dug into research on that and quickly found [this study](http://www.efmaefm.org/0EFMAMEETINGS/EFMA%20ANNUAL%20MEETINGS/2010-Aarhus/EFMA2010_0161_fullpaper.pdf) found \"\"a high positive correlation between returns on two matching stocks with similar ticker symbols\"\".\"",
"title": ""
},
{
"docid": "550661",
"text": "Google will be issuing Class C shares (under the ticker symbol GOOCV) to current GOOG holders in the beginning of April. The Class C shares and Class A shares will then change symbols, with the Class C shares trading under GOOG. This was announced on January 30th. Details are in this benzinga article: Projected Trading Timeline March 27 - April 2 Record Date - Payment Date Class C shares commence trading on March 27 as GOOCV on a when issued basis Class A shares continue to trade as GOOG, with entitlement to Class C shares Class A shares will also trade on an ex-distribution basis, without entitlement to the Class C shares, as GOOAV April 3 EX Date The ticker for the Class A shares will change from GOOG to GOOGL The ticker for the Class C shares will change from GOOCV to GOOG and commence regular way trading The ticker for the Class A shares that traded on an ex-distribution basis - GOOAV - will be suspended",
"title": ""
},
{
"docid": "104901",
"text": "There's an interesting paper, Does Investor Attention Affect Stock Prices? (Sandhya et al), where researchers look at related stock tickers. When a large cap, better-known stock jumps, smaller firms with similar symbols also rise. Pretty nuts -- I interviewed the author of the paper [here](http://www.tradestreaming.com/?p=3745). There's also a transcript.",
"title": ""
},
{
"docid": "448938",
"text": "\"The 3-letter tickers are from a different era.... Nowadays the usage of tickers is more of a \"\"legacy\"\" tradition rather than a current necessity. As such they're no longer limited to 3 characters. And the characters don't have to be related to the actual name. For example a company named Alphabet is trading on NASDAQ under the ticker \"\"GOOGL\"\". It has 5 characters, not 3, and (almost) none of them appear in the name of the company (used to, but not anymore).\"",
"title": ""
}
] |
334
|
Depletion of nitric oxide is responsible for vasospasm.
|
[
{
"docid": "25079962",
"text": "CONTEXT Delayed cerebral vasospasm causes permanent neurological deficits or death in at least 15% of patients following otherwise successful treatment for ruptured intracranial aneurysm. Decreased bioavailability of nitric oxide has been associated with the development of cerebral vasospasm. OBJECTIVE To determine whether infusions of nitrite will prevent delayed cerebral vasospasm. DESIGN, SETTING, AND SUBJECTS A total of 14 anesthetized cynomolgus monkeys had an autologous blood clot placed around the right middle cerebral artery. Cerebral arteriography was performed before clot placement and on days 7 and 14 to assess vasospasm. The study was conducted from August 2003 to February 2004. INTERVENTIONS A 90-mg sodium nitrite intravenous solution infused over 24 hours plus a 45-mg sodium nitrite bolus daily (n = 3); a 180-mg sodium nitrite intravenous solution infused over 24 hours (n = 3); or a control saline solution infusion (n = 8). Each was infused continuously for 14 days. MAIN OUTCOME MEASURES Nitrite, S-nitrosothiol, and methemoglobin levels in blood and cerebrospinal fluid and degree of arteriographic vasospasm. RESULTS In control monkeys, mean (SD) cerebrospinal fluid nitrite levels decreased from 3.1 (1.5) micromol/L to 0.4 (0.1) micromol/L at day 7 and to 0.4 (0.4) micromol/L at day 14 (P = .03). All 8 control monkeys developed significant vasospasm of the right middle cerebral artery, which was complicated by stroke and death in 1 animal. Sodium nitrite infusions increased the nitrite and methemoglobin levels (<2.1% of total hemoglobin) in the blood and cerebrospinal fluid without evoking systemic hypotension. Nitrite infusion prevented development of vasospasm (no animals developed significant vasospasm; mean [SD] reduction in right middle cerebral artery area on day 7 after subarachnoid hemorrhage of 8% [9%] in nitrite-treated monkeys vs 47% [5%] in saline-treated controls; P<.001). There was a negative correlation between the concentration of nitrite in cerebrospinal fluid and the degree of cerebral vasospasm (P<.001). Pharmacological effects of nitrite infusion were also associated with the formation of S-nitrosothiol in cerebrospinal fluid. There was no clinical or pathological evidence of nitrite toxicity. CONCLUSION Subacute sodium nitrite infusions prevented delayed cerebral vasospasm in a primate model of subarachnoid hemorrhage.",
"title": "Nitrite infusions to prevent delayed cerebral vasospasm in a primate model of subarachnoid hemorrhage."
}
] |
[
{
"docid": "23100962",
"text": "Besides synthesizing nitric oxide (NO), purified neuronal NO synthase (nNOS) can produce superoxide (.O2-) at lower L-Arg concentrations. By using electron paramagnetic resonance spin-trapping techniques, we monitored NO and .O2- formation in nNOS-transfected human kidney 293 cells. In control transfected cells, the Ca2+ ionophore A23187 triggered NO generation but no .O2- was seen. With cells in L-Arg-free medium, we observed .O2- formation that increased as the cytosolic L-Arg levels decreased, while NO generation declined. .O2- formation was virtually abolished by the specific NOS blocker, N-nitro-L-arginine methyl ester (L-NAME). Nitrotyrosine, a specific nitration product of peroxynitrite, accumulated in L-Arg-depleted cells but not in control cells. Activation by A23187 was cytotoxic to L-Arg-depleted, but not to control cells, with marked lactate dehydrogenase release. The cytotoxicity was largely prevented by either superoxide dismutase or L-NAME. Thus, with reduced L-Arg availability NOS elicits cytotoxicity by generating .O2- and NO that interact to form the potent oxidant peroxynitrite. Regulating arginine levels may provide a therapeutic approach to disorders involving .O2-/NO-mediated cellular injury.",
"title": "Nitric oxide synthase generates superoxide and nitric oxide in arginine-depleted cells leading to peroxynitrite-mediated cellular injury."
},
{
"docid": "24338780",
"text": "BACKGROUND Interferon-gamma (IFN-gamma) is an essential cytokine in the regulation of inflammatory responses in autoimmune diseases. Little is known about its role in inflammatory heart disease. METHODS AND RESULTS We showed that IFN-gamma receptor-deficient mice (IFN-gammaR(-/-)) on a BALB/c background immunized with a peptide derived from cardiac alpha-myosin heavy chain develop severe myocarditis with high mortality. Although myocarditis subsided in wild-type mice after 3 weeks, IFN-gammaR(-/-) mice showed persistent disease. The persistent inflammation was accompanied by vigorous in vitro CD4 T-cell responses and impaired inducible nitric oxide synthase expression, together with evidence of impaired nitric oxide production in IFN-gammaR(-/-) hearts. Treatment of wild-type mice with the nitric oxide synthetase inhibitor N:-nitro-l-arginine-methyl-ester enhanced in vitro CD4 T-cell proliferation and prevented healing of myocarditis. CONCLUSIONS Our data provide evidence that IFN-gamma protects mice from lethal autoimmune myocarditis by inducing the expression of inducible nitric oxide synthase followed by the downregulation of T-cell responses.",
"title": "Lethal autoimmune myocarditis in interferon-gamma receptor-deficient mice: enhanced disease severity by impaired inducible nitric oxide synthase induction."
},
{
"docid": "46743299",
"text": "Chronic exercise upregulates endothelial nitric oxide synthase (eNOS) gene expression. Whether the expression of inducible nitric oxide synthase (iNOS) is affected by exercise is unknown. We therefore investigated the effects of chronic exercise on iNOS and eNOS expression in isolated rat aortic endothelial and smooth muscle cells separately. Five-week-old male Wistar rats were randomly divided into control and exercise groups. After 10 weeks of running training, animals were sacrificed under ether anesthesia. The standard curve quantitative competitive reverse transcriptase-polymerase chain reaction method was used to quantify NOS mRNA expression in isolated endothelial/smooth muscle cells. To evaluate the functional role of iNOS, we examined phenylephrine-induced vascular responses with or without pretreatment with aminoguanidine. We found that (1) expression of iNOS and eNOS mRNA in endothelial cells was increased by chronic exercise and (2) chronic exercise blunted phenylephrine-induced vascular responses, probably by increasing NO release via iNOS. Our results show that chronic exercise increases both iNOS and eNOS gene expression in endothelium. These alterations may be partially responsible for the change in vascular response after exercise.",
"title": "Chronic Exercise Increases Both Inducible and Endothelial Nitric Oxide Synthase Gene Expression in Endothelial Cells of Rat Aorta"
},
{
"docid": "14474178",
"text": "The objective of the present study was to determine if chicken melanoma-differentiation-associated gene 5 (MDA5) senses infectious bursal disease virus infection to induce innate immunity that bridges to adaptive immunity. During IBDV infection in HD11 cells, IBDV titers and RNA loads increased up to 3.4 × 107 plaque-forming units (PFU)/mL and 1114 ng/µL, respectively, at 24 hours postinfection (hpi). IBDV infection in HD11 cells induced significantly upregulated (p < 0.05) expression levels of chicken MDA5 (59-fold), interferon-β (IFN-β) (693-fold), dsRNA-dependent protein kinase (PKR) (4-fold), 2’, 5’-oligoadenylate synthetase (OAS) (286-fold), myxovirus resistance gene (Mx) (22-fold), interleukin-1β (IL-1β) (5-fold), IL-6 (146-fold), IL-8 (4-fold), IL-10 (4-fold), inducible nitric oxide synthase (iNOS) (15-fold), and major histocompatibility complex class I (MHC class I) (4-fold). Nitric oxide production in the culture supernatants increased significantly (p < 0.05) up to 6.5 μM at 24 hpi. The expressed chMDA5 and IBDV-derived dsRNA were localized in the cytoplasm of HD11 cells during IBDV infection. ChMDA5-knockdown HD11 cells had significantly higher (p < 0.05) IBDV RNA loads at 24 hpi and significantly lower (p < 0.05) nitric oxide production and expression levels of chicken MDA5, IFN-β, PKR, OAS, Mx, IL-1β, IL-6, IL-8, IL-12(p40), IL-18, IL-10, iNOS, MHC class I and CD86 at 24 hpi. In addition, chMDA5 overexpression in HD11 cells resulted in significantly reduced (p < 0.05) IBDV titers and RNA loads and significantly increased (p < 0.05) nitric oxide production at 16 and 24 hpi. It also resulted in significantly higher (p < 0.05) expression levels of chicken MDA5, IFN-β, PKR, OAS, Mx, IL-1β, IL-6, IL-8, IL-12(p40), IL-10 and iNOS at 2 hpi. In conclusion, the results indicate that chMDA5 senses IBDV infection in chicken macrophages, and this is associated with IBDV-induced expression of IFN-β and initiation of an innate immune response that in turn activates the adaptive immune response and limits IBDV replication.",
"title": "Role of chicken melanoma differentiation-associated gene 5 in induction and activation of innate and adaptive immune responses to infectious bursal disease virus in cultured macrophages"
},
{
"docid": "7155555",
"text": "Listeria monocytogenes is widely used as a model to study immune responses against intracellular bacteria. It has been shown that neutrophils and macrophages play an important role to restrict bacterial replication in the early phase of primary infection in mice, and that the cytokines interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) are essential for protection. However, the involved signaling pathways and effector mechanisms are still poorly understood. This study investigated mouse strains deficient for the IFN-dependent transcription factors interferon consensus sequence binding protein (ICSBP), interferon regulatory factor (IRF)1 or 2 for their capacity to eliminate Listeria in vivo and in vitro and for production of inducible reactive nitrogen intermediates (RNI) or reactive oxygen intermediates (ROI) in macrophages. ICSBP−/− and to a lesser degree also IRF2−/− mice were highly susceptible to Listeria infection. This correlated with impaired elimination of Listeria from infected peritoneal macrophage (PEM) cultures stimulated with IFN-γ in vitro; in addition these cultures showed reduced and delayed oxidative burst upon IFN-γ stimulation, whereas nitric oxide production was normal. In contrast, mice deficient for IRF1 were not able to produce nitric oxide, but they efficiently controlled Listeria in vivo and in vitro. These results indicate that (a) the ICSBP/IRF2 complex is essential for IFN-γ–mediated protection against Listeria and that (b) ROI together with additional still unknown effector mechanisms may be responsible for the anti-Listeria activity of macrophages, whereas IRF1-induced RNI are not limiting.",
"title": "Crucial Role of Interferon Consensus Sequence Binding Protein, but neither of Interferon Regulatory Factor 1 nor of Nitric Oxide Synthesis for Protection Against Murine Listeriosis"
},
{
"docid": "23122306",
"text": "In an experiment to clarify the involvement of oxygen radicals in lung carcinogenesis induced by diesel exhaust particles (DEP), we found that there is a strong relation between lung tumor response and formation of 8-hydroxydeoxyguanosine (8-OHdG) in lung DNA of mice administered DEP by repeated intratracheal instillation. Repeated intratracheal instillation of DEP also induced the activity of cytochrome P-450 reductase in the lungs as a representative enzyme of superoxide generation, and two types of nitric oxide (NO) synthase, cNOS and iNOS, in the lungs. On the other hand, activities of CuZn-superoxide dismutase (SOD) and Mn-SOD antioxidant enzymes were depressed by the instillation of DEP. These results suggest that generation of superoxide, hydroxyI radical, and nitric oxide are increased in epithelial cells in airways, and that the increased superoxide and nitric oxide react very easily to produce peroxynitrite (ONOO(-)). The peroxynitrite also produce hydroxyI radical. The hydroxyl radical may play an important role in carcinogenesis by DEP.",
"title": "Lung Carcinogenesis by Diesel Exhaust Particles and the Carcinogenic Mechanism Via Active Oxygens."
},
{
"docid": "10697096",
"text": "BACKGROUND The purpose of this study was to test the hypothesis that vasodilator responses of porcine coronary resistance arteries are increased by exercise training. METHODS AND RESULTS Yucatan miniature swine were randomly divided into groups of exercise-trained (ET) and sedentary (SED) control pigs. ET pigs were placed on a progressive treadmill training program lasting 16 to 20 weeks, and SED pigs remained inactive during the same time period. Coronary resistance arteries 64 to 157 microns in diameter were isolated for in vitro evaluation of relaxation responses to the endothelium-independent dilators sodium nitroprusside (1 x 10(-10) to 1 x 10(-4) mol/L) and adenosine (1 x 10(-10) to 1 x 10(-5) mol/L) and to bradykinin (1 x 10(-13) to 3 x 10(-7) mol/L), an endothelium-dependent agent. Relaxation responses to adenosine and sodium nitroprusside were not altered by exercise training. Endothelium-dependent relaxation to bradykinin was enhanced in coronary resistance arteries from ET pigs (IC50: ET, 0.07 +/- 0.02 nmol/L; SED, 1.59 +/- 0.09 nmol/L). To determine whether prostanoids and/or the nitric oxide synthase pathway were involved in the ET-induced changes in bradykinin-induced vasodilation, responses to bradykinin were examined in coronary resistance arteries from both ET and SED pigs in the presence of indomethacin and in the presence of nitro-monomethyl L-arginine (L-NMMA). Both indomethacin and L-NMMA produced significant inhibition of the bradykinin-induced relaxation in vessels from both groups. Despite decreased bradykinin-induced relaxation after indomethacin, bradykinin-induced vasodilation was still enhanced in vessels from the ET group. L-NMMA caused greater inhibition of the bradykinin-induced relaxation in coronary resistance arteries from ET pigs relative to arteries from SED pigs and eliminated the training-induced enhancement of the bradykinin responses. CONCLUSIONS These results suggest that exercise training enhances bradykinin-induced vasodilation through increased endothelium-derived relaxing factor/nitric oxide production by the L-arginine/nitric oxide synthase pathway.",
"title": "Vasodilator responses of coronary resistance arteries of exercise-trained pigs."
},
{
"docid": "8536018",
"text": "Nitric oxide (NO) was identified as a key player in plant defence responses approximately 20 years ago and a large body of evidence has accumulated since then supporting its role as a signalling molecule. However, there are many discrepancies in current NO detection assays and the enzymatic pathways responsible for its synthesis have yet to be determined. This has provoked strong debates concerning the function of NO in plants, even questioning its existence in planta. Here we gather data obtained using the model pathosystem Arabidopsis/Pseudomonas, which confirms the production of NO during the hypersensitive response and supports is role as a trigger of hypersensitive cell death and a mediator of defence gene expression. Finally, we discuss potential sources of NO synthesis, focusing on the role of nitrite as major substrate for NO production during incompatible interactions.",
"title": "Detection and function of nitric oxide during the hypersensitive response in Arabidopsis thaliana: where there's a will there's a way."
},
{
"docid": "21297708",
"text": "1. Nitric oxide (NO) has been suggested as a gastrointestinal neurotransmitter, mediating the gastric receptive relaxation and the relaxation in the peristaltic reflex. The aim of the present study was to measure nerve-induced NO formation in vivo in the gastrointestinal tract. 2. Formation of the nitric oxide oxidation products nitrite and nitrate during vagal nerve stimulation were measured in the anaesthetized rabbit. Microdialysis probes were inserted into the wall of the stomach and proximal colon, and nitrite and nitrate in dialysate measured by capillary electrophoresis. 3. During bilateral vagal nerve stimulation there was an increase in nitrite and nitrate formation at the level of the stomach and in nitrite formation at the level of the colon. This increase was inhibited by intravenous administration of the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME 30 mg kg-1). Furthermore, L-NAME significantly increased nerve-induced gastric and colonic contractions, as well as spontaneous colonic contractions. 4. In summary, we present a new methodological procedure for quantification of small changes in nitric oxide formation in vivo. This study provides evidence that nitric oxide is released in the stomach and colonic wall during vagal nerve activity, at concentrations able to cause inhibition of smooth muscle contractions in vivo.",
"title": "Nerve-induced release of nitric oxide in the rabbit gastrointestinal tract as measured by in vivo microdialysis."
},
{
"docid": "20381484",
"text": "S-nitrosylation of proteins by nitric oxide is a major mode of signalling in cells. S-nitrosylation can mediate the regulation of a range of proteins, including prominent nuclear proteins, such as HDAC2 (ref. 2) and PARP1 (ref. 3). The high reactivity of the nitric oxide group with protein thiols, but the selective nature of nitrosylation within the cell, implies the existence of targeting mechanisms. Specificity of nitric oxide signalling is often achieved by the binding of nitric oxide synthase (NOS) to target proteins, either directly or through scaffolding proteins such as PSD-95 (ref. 5) and CAPON. As the three principal isoforms of NOS--neuronal NOS (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS)--are primarily non-nuclear, the mechanisms by which nuclear proteins are selectively nitrosylated have been elusive. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is physiologically nitrosylated at its Cys 150 residue. Nitrosylated GAPDH (SNO-GAPDH) binds to Siah1, which possesses a nuclear localization signal, and is transported to the nucleus. Here, we show that SNO-GAPDH physiologically transnitrosylates nuclear proteins, including the deacetylating enzyme sirtuin-1 (SIRT1), histone deacetylase-2 (HDAC2) and DNA-activated protein kinase (DNA-PK). Our findings reveal a novel mechanism for targeted nitrosylation of nuclear proteins and suggest that protein-protein transfer of nitric oxide groups may be a general mechanism in cellular signal transduction.",
"title": "GAPDH Mediates Nitrosylation of Nuclear Proteins"
},
{
"docid": "42873134",
"text": "Type 1 and type 2 diabetes are characterized by progressive beta-cell failure. Apoptosis is probably the main form of beta-cell death in both forms of the disease. It has been suggested that the mechanisms leading to nutrient- and cytokine-induced beta-cell death in type 2 and type 1 diabetes, respectively, share the activation of a final common pathway involving interleukin (IL)-1beta, nuclear factor (NF)-kappaB, and Fas. We review herein the similarities and differences between the mechanisms of beta-cell death in type 1 and type 2 diabetes. In the insulitis lesion in type 1 diabetes, invading immune cells produce cytokines, such as IL-1beta, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma. IL-1beta and/or TNF-alpha plus IFN-gamma induce beta-cell apoptosis via the activation of beta-cell gene networks under the control of the transcription factors NF-kappaB and STAT-1. NF-kappaB activation leads to production of nitric oxide (NO) and chemokines and depletion of endoplasmic reticulum (ER) calcium. The execution of beta-cell death occurs through activation of mitogen-activated protein kinases, via triggering of ER stress and by the release of mitochondrial death signals. Chronic exposure to elevated levels of glucose and free fatty acids (FFAs) causes beta-cell dysfunction and may induce beta-cell apoptosis in type 2 diabetes. Exposure to high glucose has dual effects, triggering initially \"glucose hypersensitization\" and later apoptosis, via different mechanisms. High glucose, however, does not induce or activate IL-1beta, NF-kappaB, or inducible nitric oxide synthase in rat or human beta-cells in vitro or in vivo in Psammomys obesus. FFAs may cause beta-cell apoptosis via ER stress, which is NF-kappaB and NO independent. Thus, cytokines and nutrients trigger beta-cell death by fundamentally different mechanisms, namely an NF-kappaB-dependent mechanism that culminates in caspase-3 activation for cytokines and an NF-kappaB-independent mechanism for nutrients. This argues against a unifying hypothesis for the mechanisms of beta-cell death in type 1 and type 2 diabetes and suggests that different approaches will be required to prevent beta-cell death in type 1 and type 2 diabetes.",
"title": "Mechanisms of pancreatic beta-cell death in type 1 and type 2 diabetes: many differences, few similarities."
},
{
"docid": "2533768",
"text": "Clinical manifestations of diabetic nephropathy are an expression of diabetic microangiopathy. This review revisits the previously proposed Steno hypothesis and advances our hypothesis that development of endothelial cell dysfunction represents a common pathophysiological pathway of diabetic complications. Specifically, the ability of glucose to scavenge nitric oxide is proposed as the initiation phase of endothelial dysfunction. Gradual accumulation of advanced glycated end products and induction of plasminogen activator inhibitor-1, resulting in the decreased expression of endothelial nitric oxide synthase and reduced generation of nitric oxide, are proposed to be pathophysiologically critical for the maintenance phase of endothelial dysfunction. The proposed conceptual shift toward the role of endothelial dysfunction in diabetic complications may provide new strategies for their prevention.",
"title": "Workshop: endothelial cell dysfunction leading to diabetic nephropathy : focus on nitric oxide."
},
{
"docid": "38944245",
"text": "Lung Krüppel-like factor (LKLF/KLF2) is an endothelial transcription factor that is crucially involved in murine vasculogenesis and is specifically regulated by flow in vitro. We now show a relation to local flow variations in the adult human vasculature: decreased LKLF expression was noted at the aorta bifurcations to the iliac and carotid arteries, coinciding with neointima formation. The direct involvement of shear stress in the in vivo expression of LKLF was determined independently by in situ hybridization and laser microbeam microdissection/reverse transcriptase-polymerase chain reaction in a murine carotid artery collar model, in which a 4- to 30-fold induction of LKLF occurred at the high-shear sites. Dissection of the biomechanics of LKLF regulation in vitro demonstrated that steady flow and pulsatile flow induced basal LKLF expression 15- and 36-fold at shear stresses greater than approximately 5 dyne/cm2, whereas cyclic stretch had no effect. Prolonged LKLF induction in the absence of flow changed the expression of angiotensin-converting enzyme, endothelin-1, adrenomedullin, and endothelial nitric oxide synthase to levels similar to those observed under prolonged flow. LKLF repression by siRNA suppressed the flow response of endothelin-1, adrenomedullin, and endothelial nitric oxide synthase (P < 0.05). Thus, we demonstrate that endothelial LKLF is regulated by flow in vivo and is a transcriptional regulator of several endothelial genes that control vascular tone in response to flow.",
"title": "Endothelial KLF2 links local arterial shear stress levels to the expression of vascular tone-regulating genes."
},
{
"docid": "46328296",
"text": "Patients with essential hypertension exhibit blunted endothelium-dependent vasodilator responses, which may be largely attributable to reduced bioactivity of nitric oxide (NO). Therefore, we measured the end product of NO, nitrate plus nitrite (nitrogen oxide), and examined the relationship between the degree of hypertension and plasma nitrate plus nitrite levels in patients with essential hypertension. The combined plasma concentration of nitrate plus nitrite, end products of NO metabolism, was reduced in individuals with essential hypertension relative to that in control subjects (15.7+/-1.1 versus 22.8+/-1.4 mmol x L(-1), P<.001); individuals with borderline hypertension showed values that were intermediate between those of the other two groups (18.2+/-1.2 mmol x L(-1), P<.001). The plasma nitrogen oxide concentration showed significant inverse correlations with both systolic and diastolic blood pressures. The basal concentration of nitrogen oxide in the plasma was reduced, at least in the peripheral circulation, in individuals with essential hypertension.",
"title": "Reduced plasma concentrations of nitrogen oxide in individuals with essential hypertension."
},
{
"docid": "7230315",
"text": "The high-output pathway of nitric oxide production helps protect mice from infection by several pathogens, including Mycobacterium tuberculosis. However, based on studies of cells cultured from blood, it is controversial whether human mononuclear phagocytes can express the corresponding inducible nitric oxide synthase (iNOS;NOS2). The present study examined alveolar macrophages fixed directly after bronchopulmonary lavage. An average of 65% of the macrophages from 11 of 11 patients with untreated, culture-positive pulmonary tuberculosis reacted with an antibody documented herein to be monospecific for human NOS2. In contrast, a mean of 10% of bronchoalveolar lavage cells were positive from each of five clinically normal subjects. Tuberculosis patients' macrophages displayed diaphorase activity in the same proportion that they stained for NOS2, under assay conditions wherein the diaphorase reaction was strictly dependent on NOS2 expression. Bronchoalveolar lavage specimens also contained NOS2 mRNA. Thus, macrophages in the lungs of people with clinically active Mycobacterium tuberculosis infection often express catalytically competent NOS2.",
"title": "Inducible nitric oxide synthase in pulmonary alveolar macrophages from patients with tuberculosis"
},
{
"docid": "6580081",
"text": "Ischemia-reperfusion injury is, at least in part, responsible for the morbidity associated with liver surgery under total vascular exclusion or after liver transplantation. The pathophysiology of hepatic ischemia-reperfusion includes a number of mechanisms that contribute to various degrees in the overall injury. Some of the topics discussed in this review include cellular mechanisms of injury, formation of pro- and anti-inflammatory mediators, expression of adhesion molecules, and the role of oxidant stress during the inflammatory response. Furthermore, the roles of nitric oxide in preventing microcirculatory disturbances and as a substrate for peroxynitrite formation are reviewed. In addition, emerging mechanisms of protection by ischemic preconditioning are discussed. On the basis of current knowledge, preconditioning or pharmacological interventions that mimic these effects have the greatest potential to improve clinical outcome in liver surgery involving ischemic stress and reperfusion.",
"title": "Molecular mechanisms of hepatic ischemia-reperfusion injury and preconditioning."
},
{
"docid": "14711483",
"text": "CONTEXT Vaso-occlusion is central to the painful crises and acute and chronic organ damage in sickle cell disease. Abnormal nitric oxide-dependent regulation of vascular tone, adhesion, platelet activation, and inflammation contributes to the pathophysiology of vaso-occlusion. Nitric oxide may have promise as a mechanism-of-disease-based therapy for treatment of vaso-occlusion. OBJECTIVE To explore the efficacy and safety of inhaled nitric oxide (INO) for treatment of vaso-occlusive crisis in pediatric patients. DESIGN Prospective, double-blind, placebo-controlled, randomized clinical trial with enrollment between September 1999 and October 2001. SETTING Urban, tertiary care children's hospital in the United States. PARTICIPANTS Twenty patients aged 10 to 21 years with sickle cell disease and severe acute vaso-occlusive crisis. INTERVENTION Patients were randomly assigned to receive INO (80 ppm with 21% final concentration of inspired oxygen; n = 10), or placebo (21% inspired oxygen; n = 10) for 4 hours. MAIN OUTCOME MEASURES Change in pain at 4 hours of inhalation compared with preinhalation pain, measured on a 10-cm visual analog scale (VAS); secondary outcome measures were pain over 6 hours, parenteral narcotic use over 24 hours, duration of hospitalization, blood pressure, oxygen saturation, and methemoglobin concentration. RESULTS Preinhalation VAS pain scores were similar in the INO and placebo groups (P =.80). The decrease in VAS pain scores at 4 hours was 2.0 cm in the INO group and 1.2 cm in the placebo group (P =.37). Repeated-measures analysis of variance for hourly pain scores showed a 1-cm/h greater reduction in the INO group than the placebo group (P =.02). Morphine use over 6 hours was significantly less in the INO group (mean cumulative use, 0.29 vs 0.44 mg/kg; P =.03) but was not different over 4 hours (0.26 vs 0.32 mg/kg; P =.21) or 24 hours (0.63 vs 0.91 mg/kg; P =.15). Duration of hospitalization was 78 and 100 hours in the INO and placebo groups, respectively (P =.19). No INO toxicity was observed. CONCLUSIONS Results of this exploratory study suggest that INO may be beneficial for acute vaso-occlusive crisis. These preliminary results warrant further investigation.",
"title": "Preliminary assessment of inhaled nitric oxide for acute vaso-occlusive crisis in pediatric patients with sickle cell disease."
},
{
"docid": "12582729",
"text": "BACKGROUND Upregulated by atheroprotective flow, the transcription factor Krüppel-like factor 2 (KLF2) is crucial for maintaining endothelial function. MicroRNAs (miRNAs) are noncoding small RNAs that regulate gene expression at the posttranscriptional level. We examined the role of miRNAs, particularly miR-92a, in the atheroprotective flow-regulated KLF2. METHODS AND RESULTS Dicer knockdown increased the level of KLF2 mRNA in human umbilical vein endothelial cells, suggesting that KLF2 is regulated by miRNA. In silico analysis predicted that miR-92a could bind to the 3' untranslated region of KLF2 mRNA. Overexpression of miR-92a decreased the expression of KLF2 and the KLF2-regulated endothelial nitric oxide synthase and thrombomodulin at mRNA and protein levels. A complementary finding is that miR-92a inhibitor increased the mRNA and protein expression of KLF2, endothelial nitric oxide synthase, and thrombomodulin. Subsequent studies revealed that atheroprotective laminar flow downregulated the level of miR-92a precursor to induce KLF2, and the level of this flow-induced KLF2 was reduced by miR-92a precursor. Furthermore, miR-92a level was lower in human umbilical vein endothelial cells exposed to the atheroprotective pulsatile shear flow than under atheroprone oscillatory shear flow. Anti-Ago1/2 immunoprecipitation coupled with real-time polymerase chain reaction revealed that pulsatile shear flow decreased the functional targeting of miR-92a precursor/KLF2 mRNA in human umbilical vein endothelial cells. Consistent with these findings, mouse carotid arteries receiving miR-92a precursor exhibited impaired vasodilatory response to flow. CONCLUSIONS Atheroprotective flow patterns decrease the level of miR-92a, which in turn increases KLF2 expression to maintain endothelial homeostasis.",
"title": "Flow-Dependent Regulation of Kruppel-Like Factor 2 Is Mediated by MicroRNA-92a."
},
{
"docid": "15561961",
"text": "Hypercholesterolemia is associated with impairments in endothelium-dependent vascular relaxations. Paradoxically, endothelial production of nitrogen oxides is increased in early stages of hypercholesterolemia. Prior work has shown that oxidized low density lipoprotein (LDL) has both stimulatory and inhibitory effects on endothelial nitric oxide synthase expression (eNOS) and has focused on lysophosphatidyl choline (LPC) as a component of oxidized LDL which may modulate this effect. Another biologically active component of oxidized LDL is 13-hydroperoxyoctadecadienoic acid (13-HPODE), an oxidized form of linoleic acid. The purpose of this study was to determine the effect of HPODE on the expression of eNOS in bovine aortic endothelial cells (BAECs). Twenty four hour treatment of endothelial cells with HPODE caused a dose-dependent increase in eNOS mRNA levels as assessed by Northern analysis. The time response studies show that HPODE treatment significantly increased eNOS mRNA levels at 12 and 24 h. Concomitant with the increase in eNOS mRNA levels, 20 microM HPODE treatment significantly increased eNOS protein content and enzyme activity. Nuclear run-on studies indicated that the rate of transcription of eNOS gene was significantly elevated 4 h after HPODE treatment when compared to control cultures. Also, actinomycin D studies demonstrated that the half-life of eNOS mRNA was increased from 6 h to 12 h by HPODE treatment. Thus, HPODE-induced up-regulation of eNOS expression is mediated by both transcriptional and posttranscriptional mechanisms. These observations suggest that endothelial cells may attempt to compensate for oxidative injury by increasing expression of eNOS in early stages of hypercholesterolemia.",
"title": "expression by oxidized linoleic"
},
{
"docid": "28207326",
"text": "Vascular endothelial growth factor-A (VEGF-A) is a protein secreted by podocytes that is necessary for survival of endothelial cells, podocytes, and mesangial cells. VEGF-A regulates slit-diaphragm signaling and podocyte shape via VEGF-receptor 2-nephrin-nck-actin interactions. Chronic hyperglycemia-induced excess podocyte VEGF-A and low endothelial nitric oxide drive the development and the progression of diabetic nephropathy. The abnormal cross-talk between VEGF-A and nitric oxide pathways is fueled by the diabetic milieu, resulting in increased oxidative stress. Recent findings on these pathogenic molecular mechanisms provide new potential targets for therapy for diabetic renal disease.",
"title": "VEGF and podocytes in diabetic nephropathy."
},
{
"docid": "26658659",
"text": "Hydrogen sulfide (H(2)S) was recently discovered to be synthesized in mammalian tissues by several different enzymes. Numerous studies have shown that H(2)S has vasodilator and antihypertensive effects in the cardiovascular system. However, intracellular mechanisms of the H(2)S-induced vasodilation and its interactions with other endothelium-derived relaxing factors, such as nitric oxide (NO), remain unclear. We investigated whether H(2)S directly regulates endothelial NO synthase (eNOS) activity and NO production in endothelial cells. NaHS, a H(2)S donor, dose-dependently increased NO production in cultured endothelial cells. This effect was abolished by a calcium chelator (BAPTA-AM), but not by the absence of extracellular calcium. The NaHS-induced NO production was partially blocked by inhibitors of ryanodine receptor (dantrolene) or inositol 1,4,5-triphosphate receptor (xestospongin C). NaHS significantly increased intracellular calcium concentrations, and this effect was attenuated by dantrolene or xestospongin C. NaHS induced phosphorylation of eNOS at the activating phosphoserine residue 1179. The NaHS-induced eNOS phosphorylation and NO production were not affected by a PI3K/Akt inhibitor (wortmannin). The data of this study suggest that H(2)S directly acts on endothelial cells to induce eNOS activation and NO production by releasing calcium from the intracellular store in endoplasmic reticulum, which may explain one of mechanisms of its vasodilator function.",
"title": "Hydrogen sulfide increases nitric oxide production with calcium-dependent activation of endothelial nitric oxide synthase in endothelial cells."
},
{
"docid": "5785219",
"text": "Nitric oxide (NO) is a product of L-arginine metabolism that suppresses cellular oxidative metabolism through the inhibition of tricarboxylic acid cycle and electron transport chain enzymes. The impact of NO synthase (NOS) activity on specific pathways of glucose metabolism in freshly harvested and overnight-cultured rat resident peritoneal macrophages, at rest and after stimulation with zymosan, was investigated using radiolabeled glucose. NOS activity was modulated through the L-arginine concentration in culture media and the use of its specific inhibitor, NG-monomethyl-L-arginine, and quantitated using radiolabeled L-arginine. Results demonstrated that NOS activity was associated with increased glucose disappearance, glycolysis, and hexose monophosphate shunt activity and, in line with the known inhibition of oxidative metabolism associated with the production of NO, with a decrease in the flux of glucose and butyrate carbon through the tricarboxylic acid cycle. In addition, the relative increase in glucose utilization that follows zymosan stimulation was enhanced by treatments that suppressed NOS activity. These results demonstrate that the characteristics of glucose metabolism by macrophages are, to a significant extent, determined by products of NOS.",
"title": "Modulation of glucose metabolism in macrophages by products of nitric oxide synthase."
},
{
"docid": "6923795",
"text": "Cytochrome P450 (P450)-dependent metabolites of arachidonic acid, the epoxyeicosatrienoic acids (EETs), are proposed to be endothelium-derived hyperpolarizing factors (EDHF) that affect vascular tone; however, the effects of EDHF on endothelial-derived nitric oxide biosynthesis remain unknown. We examined the regulation of endothelial nitric-oxide synthase (eNOS) by EDHF and investigated the relevant signaling pathways involved. The P450 epoxygenases CYP102 F87V mutant, CYP2C11-CYPOR, and CYP2J2 were transfected into cultured bovine aortic endothelial cells, and the effects of endogenously formed or exogenously applied EETs on eNOS expression and activity were assessed. Transfection with the P450 epoxygenases led to increased eNOS protein expression, an effect that was attenuated by cotreatment with the P450 inhibitor 17-ODYA. Northern analysis demonstrated that P450 transfection led to increased eNOS mRNA levels consistent with an effect at the pretranslational level. P450 epoxygenase transfection resulted in increased eNOS activity as measured by the conversion of L-arginine to L-citrulline. Addition of synthetic EETs (50-200 nM) to the culture media also increased eNOS expression and activity. Treatment with mitogen-activated protein kinase (MAPK), MAPK kinase, and protein kinase C inhibitors apigenin, 2'-amino-3'-methoxyflavone (PD98059), and 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7), respectively, significantly inhibited the effects of P450 transfection on eNOS expression. Overexpression of P450 epoxygenases or addition of synthetic EETs increased Thr495 phosphorylation of eNOS, an effect that was inhibited by both apigenin and PD98059. Overexpression of P450 epoxygenases in rats resulted in increased aortic eNOS expression, providing direct evidence that EDHF can influence vascular eNOS levels in vivo. Based on this data, we conclude that EDHF up-regulates eNOS via activation of MAPK and protein kinase C signaling pathways.",
"title": "Up-regulation of endothelial nitric-oxide synthase by endothelium-derived hyperpolarizing factor involves mitogen-activated protein kinase and protein kinase C signaling pathways."
},
{
"docid": "24705390",
"text": "BACKGROUND & AIMS Helicobacter pylori is an important etiologic factor in the development of gastric cancer. The aim of this study was to analyze the role of H. pylori infections in the induction of mutagenic events in gastric epithelial cells. The effect of a high-salt diet as a genotoxic risk factor was also investigated. METHODS Big Blue transgenic male mice (C57Bl/6) were inoculated with H. pylori (strain SS1) or Helicobacter felis (strain CS1) for 6 and 12 months. The frequency and spectrum of mutations at the stomach level were assessed. Inflammatory host response and inducible nitric oxide synthase (iNOS) expression by reverse-transcription polymerase chain reaction and immunohistochemistry analysis were also performed. RESULTS After 6 months, the gastric mutant frequency was 4-fold and 1.7-fold higher in mice infected with H. pylori and H. felis, respectively, than in uninfected mice. It was associated with a high frequency of transversions (AT --> CG and GC --> TA) known to result from oxidative damages. The Helicobacter-infected mice exhibited severe gastritis and a high level of iNOS messenger RNA expression. Hyperplasia developed 12 months after inoculation, and both the mutagenic effects and iNOS expression decreased in H. pylori- and H. felis-infected mice. No synergistic effects of a high-salt diet and Helicobacter infection were observed regarding the frequency of gastric mutation. CONCLUSIONS A direct gastric mutagenic effect due to H. pylori infection in the Big Blue transgenic mouse model has been shown 6 months after inoculation. This genotoxicity can be attributable to oxidative DNA damage involving the inflammatory host response.",
"title": "Chronic Helicobacter pylori infections induce gastric mutations in mice."
},
{
"docid": "22995164",
"text": "Nitrosoglutathione [(GSNO), 500 nmol/l] relaxed the norepinephrine precontracted rat aortic rings. The relaxation effect was pronouncedly enhanced by H2S- and HS−-donor NaHS (30 μmol/l) at 7.5 pH but not at 6.3 pH. To study molecular mechanism of this effect, we investigated whether NaHS can release NO from NO donors. Using an electron paramagnetic resonance spectroscopy method of spin trap and by measuring the NO oxidation product, which is nitrite, by the Griess reaction, we report that NaHS released NO from nitrosothiols, namely from GSNO, S-nitroso-N-acetyl-dl-penicillamine (SNAP), from metal nitrosyl complex nitroprusside (SNP) and from rat brain homogenate and murine L1210 leukaemia cells. From the observation that the releasing effect was more pronounced at 8.0 pH than 6.0 pH, we suppose that HS−, rather than H2S, is responsible for the NO-releasing effect. Since in mammals, H2S and HS− are produced endogenously, we assume that their effect to release NO from nitrosothiols and from metal nitrosyl complexes are responsible for some of their biological activities and that this mechanism may be involved in S-nitrosothiol-signalling reactions.",
"title": "H2S and HS− donor NaHS releases nitric oxide from nitrosothiols, metal nitrosyl complex, brain homogenate and murine L1210 leukaemia cells"
},
{
"docid": "32985041",
"text": "Nitric oxide (NO) has been linked to numerous physiological and pathophysiological events that are not readily explained by the well established effects of NO on soluble guanylyl cyclase. Exogenous NO S-nitrosylates cysteine residues in proteins, but whether this is an important function of endogenous NO is unclear. Here, using a new proteomic approach, we identify a population of proteins that are endogenously S-nitrosylated, and demonstrate the loss of this modification in mice harbouring a genomic deletion of neuronal NO synthase (nNOS). Targets of NO include metabolic, structural and signalling proteins that may be effectors for neuronally generated NO. These findings establish protein S-nitrosylation as a physiological signalling mechanism for nNOS.",
"title": "Protein S-nitrosylation: a physiological signal for neuronal nitric oxide"
},
{
"docid": "79447",
"text": "OBJECTIVE The purpose of this study was to characterize the relationship between adipose tissue phenotype and depot-specific microvascular function in fat. METHODS AND RESULTS In 30 obese subjects (age 42±11 years, body mass index 46±11 kg/m(2)) undergoing bariatric surgery, we intraoperatively collected visceral and subcutaneous adipose tissue and characterized depot-specific adipose phenotypes. We assessed vasomotor function of the adipose microvasculature using videomicroscopy of small arterioles (75-250 μm) isolated from different fat compartments. Endothelium-dependent, acetylcholine-mediated vasodilation was severely impaired in visceral arterioles, compared to the subcutaneous depot (P<0.001 by ANOVA). Nonendothelium dependent responses to papaverine and nitroprusside were similar. Endothelial nitric oxide synthase inhibition with N(ω)-nitro-l-arginine methyl ester reduced subcutaneous vasodilation but had no effect on severely blunted visceral arteriolar responses. Visceral fat exhibited greater expression of proinflammatory, oxidative stress-related, hypoxia-induced, and proangiogenic genes; increased activated macrophage populations; and had a higher capacity for cytokine production ex vivo. CONCLUSIONS Our findings provide clinical evidence that the visceral microenvironment may be intrinsically toxic to arterial health providing a potential mechanism by which visceral adiposity burden is linked to atherosclerotic vascular disease. Our findings also support the evolving concept that both adipose tissue quality and quantity may play significant roles in shaping cardiovascular phenotypes in human obesity.",
"title": "Arteriolar function in visceral adipose tissue is impaired in human obesity."
},
{
"docid": "11181416",
"text": "Because arginase hydrolyzes arginine to produce ornithine and urea, it has the potential to regulate nitric oxide (NO) and polyamine synthesis. We tested whether expression of the cytosolic isoform of arginase (arginase I) was limiting for NO or polyamine production by activated RAW 264.7 macrophage cells. RAW 264.7 cells, stably transfected to overexpress arginase I or beta-galactosidase, were treated with interferon-gamma to induce type 2 NO synthase or with lipopolysaccharide or 8-bromo-cAMP (8-BrcAMP) to induce ornithine decarboxylase. Overexpression of arginase I had no effect on NO synthesis. In contrast, cells overexpressing arginase I produced twice as much putrescine after activation than did cells expressing beta-galactosidase. Cells overexpressing arginase I also produced more spermidine after treatment with 8-BrcAMP than did cells expressing beta-galactosidase. Thus endogenous levels of arginase I are limiting for polyamine synthesis, but not for NO synthesis, by activated macrophage cells. This study also demonstrates that it is possible to alter arginase I levels sufficiently to affect polyamine synthesis without affecting induced NO synthesis.",
"title": "Arginase I: a limiting factor for nitric oxide and polyamine synthesis by activated macrophages?"
},
{
"docid": "43048059",
"text": "AIMS The present study aims to investigate the interaction between nitric oxide (NO) and hydrogen sulfide (H(2)S), the two important gaseous mediators in rat hearts. METHODS AND RESULTS Intracellular calcium in isolated cardiomyocytes was measured with a spectrofluorometric method using Fura-2. Myocyte contractility was measured with a video edge system. NaHS (50 µM, an H(2)S donor) had no significant effect on the resting calcium level, electrically induced (EI) calcium transients, and cell contractility in ventricular myocytes. Stimulating endogenous NO production with l-arginine or exogenous application of NO donors [sodium nitroprusside (SNP) and 2-(N,N-diethylamino)-diazenolate-2-oxide] decreased myocyte twitch amplitudes accompanied by slower velocities of both cell contraction and relaxation. Surprisingly, NaHS reversed the negative inotropic and lusitropic effects of the above three NO-increasing agents. In addition, the mixture of SNP + NaHS increased, whereas SNP alone decreased, the resting calcium level and the amplitudes of EI calcium transients. Angeli's salt, a nitroxyl anion (HNO) donor, mimicked the effect of SNP + NaHS on calcium handling and myocyte contractility. Three thiols, N-acetyl-cysteine, l-cysteine, and glutathione, abolished the effects of HNO and SNP + NaHS on myocyte contraction. Neither Rp-cAMP [a protein kinase A (PKA) inhibitor] nor Rp-cGMP [a protein kinase G (PKG) inhibitor] affected the effects of SNP + NaHS, suggesting a cAMP/PKA- or cGMP/PKG-independent mechanism. CONCLUSION H(2)S may interact with NO to form a thiol sensitive molecule (probably HNO) which produces positive inotropic and lusitropic effects. Our findings may shed light on the interaction of NO and H(2)S and provide new clues to treat cardiovascular diseases.",
"title": "Hydrogen sulfide interacts with nitric oxide in the heart: possible involvement of nitroxyl."
},
{
"docid": "23513718",
"text": "Responses of cerebral blood vessels to nitric oxide (NO) are mediated by soluble guanylate cyclase (sGC)-dependent and potentially by sGC-independent mechanisms. One sGC-independent mechanism by which NO may produce vasodilatation is inhibition of formation of a vasoconstrictor metabolite produced through the cytochrome P450 pathway. In these experiments, we examined the hypothesis that dilatation of cerebral microvessels in response to NO is dependent on activation of sGC. Diameters of cerebral arterioles (baseline diameter=94+/-5 micrometers, mean+/-S.E.) were measured using a closed cranial window in anesthetized rabbits. Under control conditions, YC-1 [3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole], an NO-independent activator of sGC, produced vasodilation that was blocked by ODQ (1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one)(10 microM), an inhibitor of sGC. These findings indicate that sGC is functionally important in cerebral arterioles. In addition, acetylcholine (which stimulates endogenous production of NO by endothelium) produced dilatation of cerebral arterioles that was inhibited by ODQ. For example, 1 microM acetylcholine dilated cerebral arterioles by 34+/-7 and 5+/-1% in the absence and presence of ODQ (10 microM), respectively. Increases in arteriolar diameter in response to sodium nitroprusside (1 microM, an NO donor) were inhibited by approximately 80% by ODQ, but were not affected by 17-ODYA (10 microM) or clotrimazole (10 microM), inhibitors of the cytochrome P450 pathway. Thus, dilatation of the cerebral microcirculation in response to exogenously applied and endogenously produced NO is dependent, in large part, on activation of sGC.",
"title": "Role of soluble guanylate cyclase in dilator responses of the cerebral microcirculation."
}
] |
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